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Analysis of RNA for transcripts for catalase and SP71 in rat hearts after in vivo hyperthermia. Hyperthermic stress induces synthesis of the major inducible (heat) stress protein (SP71) in all rat tissues. In addition, there is an increase in catalase activity in hearts at 24 and 48 h after the induction of the heat shock response. To more precisely define some of the molecular aspects of the induction of the heat shock response in hearts, we examined mRNA levels for the catalase, SP71 and HSP27. RNA was isolated from control hearts and at various time periods (0-24 h) of recovery after brief hyperthermic treatment and was analyzed by Northern blot analysis using as probes cDNA sequences for rat liver catalase, human HSP70 (inducible), and human HSP27. There was no detectable change in mRNA for catalase after heat shock or during recovery. Hyperthermic stress has no apparent effect on the regulation of transcription of mRNA coding for catalase, indicating that the increase in catalase activity is either translationally or post-translationally regulated. The human HSP70 cDNA did not hybridize to control heart RNA, but did hybridize to SP71 transcripts at 0, 1.5, and 3 h post heat shock. The mRNA level for SP71 peaked at 1.5 h, was reduced at 3 h, and became almost undetectable at 6 h post heat shock. Similarly, the human HSP27 cDNA did not hybridize to control heart RNA, but did hybridize to transcripts for HSP27 at 0, 1.5, 3, and up to 15 h post heat shock. Maximal signal for HSP27 was at 3 h post heat shock and was sharply reduced at 6 h post heat shock.(ABSTRACT TRUNCATED AT 250 WORDS)

[Development of the sense of smell, a review]. The pre- and postnatal development of human olfaction is described. Data from animal experiments a partially reviewed as a base for understanding of the results of olfactory testing of babies and children. In rat fetuses the vomero-nasal-organ is used as detector of molecules in the amnion fluid. The perinatal aeration of the nasal cavity allows the adequate stimulation of the olfactory epithelium. The early postnatal olfaction is a brainstem function; later the olfactory cortical area are used for the discrimination between odorants. There are only a few investigations about the olfactory function in childhood, so that the testing of olfaction for detecting abnormal brain developments is just in the beginning.

Isolation and characterization of a 1-beta-D-arabinofuranosylcytosine-resistant Chinese hamster ovary cell mutant that is also X-ray sensitive and is noncomplementary with ataxia telangiectasia cells. In order to study the mechanism of induction of mutations and chromosome aberrations by ionizing radiations, it is particularly useful to have available radiation-sensitive mutants. While several X-ray-sensitive rodent cell lines are available, they have been selected rather nonspecifically. It was determined that selection for resistance to the DNA replication/repair inhibitor, 1-beta-D-arabinofuranosylcytosine (ara-C), would permit production of a set of X-ray-sensitive mutant cell lines that would be defective in the resynthesis step of excision or recombination repair. Such mutant cells could also be used for the isolation and characterization of human DNA repair genes. In particular, it was predicted that the repair gene defective in individuals with ataxia telangiectasia (AT) might be amenable to study with ara-C-resistant (X-ray-sensitive) mutants, since additional studies, presented here, have shown that AT cells are resistant to ara-C. In the long term, it is hoped that determining the specific defect in AT might lead to an understanding of the possible role of defective repair in tumor induction and/or progression. The general approach used to isolate ara-C-resistant Chinese hamster ovary cell mutants was to treat cells with ethyl methanesulfonate and select in increasing concentrations of ara-C. Although several mutants were isolated, one in particular, Ara-CR213, has been studied most extensively. It was selected largely because it shows the greatest sensitivity to X-rays. Ara-CR213 cells were hypersensitive to the killing effect of X-rays with an LD10 of 2.5 Gy as compared to the wild-type cells that had an LD10 of 6 Gy. The mutant showed an increased frequency of X-ray-induced chromosomal aberrations in the G1 and G2 stages of the cell cycle compared to wild-type frequencies. There was no increase in sister chromatid exchange levels. All of these observations in Ara-CR213 are very similar to those made with AT cells in our and other laboratories. Even more important, complementation analysis of Ara-CR213 x AT hybrid cells indicated that the gene responsible for X-ray sensitivity of AT is also mutated in Ara-CR213 cells. Thus, Ara-CR213 appears to have a mutant phenotype and probably genotype that is very similar to, if not exactly the same as, those of AT. This makes it quite different from other X-ray-sensitive cells that have been isolated in other laboratories.

Effects of D-penicillamine on neuromuscular transmission in rats. Treatment of patients with D-penicillamine (D-P) has been associated with a syndrome similar to myasthenia gravis (MG). To explore this association, we examined the effects of D-P on neuromuscular transmission in rat muscle. In the first experiment, bath-applied D-P had no significant effect on either miniature endplate potential (MEPP) amplitude or action potential (AP) amplitude. Endplate potential (EPP) amplitude and spontaneous MEPP frequency decreased significantly at concentrations approximately 40 times the maximum human therapeutic level. In the second experiment, rats receiving D-P by daily injections for 33 to 37 days did not differ from controls in any of the measured electrophysiologic characteristics. Electron microscopy of muscle endplates from rats treated with D-P showed no evidence of degeneration or simplification. In all cases, thymus histology by light microscopy was normal, and no antireceptor antibodies were found. Thus, D-P has a mild direct presynaptic effect on neuromuscular transmission at high concentrations, but this effect is too small to account for the weakness seen in the myasthenia-like syndrome in humans.

Pregnancies in the presence of copper intra-uterine devices. Hysterosalpingographic studies. Two copper-bearing intrauterine devices--the Cu-7 and Cu-T-200--were investigated to determine why contraceptive failures occur with these devices. For this investigation, 155 multiparous women were followed up for at least 24 months after IUD insertion (T-Cu-200 in 75 cases and the Cu-7 in 80 cases). Three women using the T-Cu-200 and 5 women using the Cu-7 became pregnant during the first year. Hysterosalpingographic findings are presented for 8 of these cases and for 2 additional cases (one with each device) who became pregnant during the second year of follow-up. These indicate that uterine abnormalities and disproportions between the uterine cavity's shape and size and that of the device are the primary reasons for device displacement and partial fundal coverage leading to contraceptive failures.

Accurate counting of low numbers of leukocytes. Use of flow cytometry and a manual low-count chamber. The leukocyte depletion that current filters make possible in erythrocyte and platelet preparations can result in leukocyte concentrations too low to be counted accurately by automated and standard manual methods. A recently described method for counting low numbers (1 to 10 x 10(6) per L) of leukocytes by flow cytometry and the use of a manual low-count chamber on 25 venous samples serially diluted to 1:1,000 were evaluated. The results show that both methods for counting leukocytes can reliably determine counts of 1 to 10 x 10(6) leukocytes/liter (a three-order of magnitude reduction from venous blood) in terms of order of magnitude but lack accuracy for specific measurement. The flow cytometric method is more expensive, less readily available, and suffers from greater sample variability. Use of a low-count chamber is a superior technique to evaluate and maintain quality control of methods for leukocyte depletion, resulting in a final leukocyte concentration of 1 to 10 cells per microliter.

The glial cells of the cerebral ganglia of Helix pomatia L. (Gastropoda, Pulmonata). II. Uptake of ferritin and 3H-glutamate. 1. With Helix pomatia intracerebral injections of ferritin were carried out (maximal incubation time: 45 min). First, the marker spreads with time via the enxtracellular space throughout the cerebral ganglia and, secondly, is transported out of the ganglia. Electron microscopical studies showed that all glial cell types take up great amounts of ferritin by endocytosis. The plasmatic glial cells at the periphery incorporate more of the marker than the filamentous glial cells in the centre. No uptake of ferritin by neurons or axons was observed. In vitro studies proved that ferritin can penetrate from the connective tissue capsule into the ganglia only after disruption of the neural lamella and damaging of the peripheral glial processes. 2. 3H-glutamate, a putative transmitter of the CNS of Helix pomatia, was injected into the hemocoel of active snails (incubation times: 15 min, 1h, 6h, 3d). Light microscopical evaluation of radioautographs showed that great quantities of the tracer penetrate into the ganglia. The bulk of it is taken up by glial cells, whereas the neurons exhibit only small amounts of the tracer. The studies with ferritin as well as those with 3H-glutamate indicate that the glial cells of the cerebral ganglia of Helix pomatia act as a "hemolymph-neuron barrier". A dominant role of the plasmatic glial cells according to these processes is discussed.

Prevention of ischemic orchitis during inguinal hernioplasty. Ischemic orchitis and testicular atrophy remain the most dreaded complications of inguinal hernioplasties. The current study examines these complications in a series of hernia repairs during a period of 20 years. The incidence of the complications in the ten year period from 1971 to 1981 was compared with the experience since 1981, from which time all distal indirect hernia sacs were left in place and increasing experience was gained in properitoneal repairs of recurrent hernias. The incidence of ischemic orchitis in primary hernia repairs was reduced from 0.65 per cent (11 instances in 1,682 repairs) to 0.03 per cent (one in 3,634 repairs). The incidence in recurrent hernia repairs was reduced from 2.25 per cent (seven in 311 repairs) to 0.97 per cent (eight in 827 repairs). These data have led us to emphasize the importance of minimizing cord dissection by leaving intact all significant distal hernia sacs and not dissecting beyond the pubic tubercle. Additionally, properitoneal repairs should be considered for repairs of recurrent hernias not only to reduce further recurrences but also to avoid testicular complications.

Isolation of a carotenoid-containing sub-membrane particle from the chloroplastic envelope outer membrane of pea (Pisum sativum). Chloroplastic envelope membranes isolated from pea (Pisum sativum) leaves are rich in carotenoids, containing approximately 2 micrograms of carotenoid mg-1 protein. We report here that envelopes can be surfactant-solubilized while maintaining association of carotenoids with protein components of the membrane. Treatment of isolated chloroplastic envelope membranes with 0.5% Deriphat 160 (N-lauryl-beta-imminodipropionate) causes general solubilization but preserves an envelope sub-membrane fragment which is fractionated by centrifugation in a sucrose gradient and by chromatography on a column of DEAE-Sephacel. The isolated submembrane complex contained five major proteins with M(r) values equivalent to 75,000, 36,000, 34,000 17,500, and 14,500. Spectroscopic and chromatographic analyses revealed that the complex contains violaxanthin and at least one other carotenoid. Carotenoid content of the fractionated complex was estimated as 4.8 micrograms mg-1 protein. Immunoblot analysis reveals that the constituent proteins of this complex are derived from the chloroplastic outer envelope membrane. These data suggest that at least some of the carotenoids of the chloroplastic envelope may be organized by apoproteins.

Neuropathologic changes with experimental spinal instrumentation: transpedicular versus sublaminar fixation. Fifty-six mature beagles underwent lumbar spine destabilization, followed by fusion using four techniques. Spinal cord neuropathologic analysis was carried out to determine the number of abnormalities within each group. Group I (n = 14) had posterolateral bone grafting without instrumentation. Group IIa (n = 14) had Cotrel-Dubousset (CD) pedicle screws and rods. Group IIb (n = 14) had Steffee pedicle screws and plates. Group III (n = 14) had sublaminar wires and rods. All of the animals remained clinically neurologically normal throughout the 6 months of the study. The incidence of moderate to severe neuropathologic changes was 21% in Group I, 18% in Group II, and 64% in Group III. Thus, a significantly higher percentage of neuropathologic abnormalities occurred with sublaminar instrumentation than with no instrumentation (p = 0.027), or with transpedicular instrumentation (p = 0.027). In this controlled animal study, the theoretical advantage of pedicle screws, which should not violate the spinal canal, over sublaminar devices, which must enter the canal, was confirmed.

Laser midline glossectomy as a treatment for obstructive sleep apnea. Multiple site specific procedures have been proposed to treat obstructive sleep apnea syndrome (OSAS). Midline glossectomy (MLG) is a procedure that directly enlarges the hypopharyngeal airspace using the carbon dioxide laser. The initial experience of 12 patients is presented. Midline glossectomy as the sole procedure was performed on 11 patients who had failed uvulopalatopharyngoplasty (UPPP) and who were felt to have significant hypopharyngeal collapse on physical examination and Müller's maneuver. One patient with primary hypopharyngeal narrowing underwent MLG. Five (42%) were considered responders with Respiratory Disturbance Index (RDI) decreasing from 60.6 per hour to 14.5 per hour. In seven nonresponders, there was no significant change in the RDI (62.6 events per hour to 48.4 events per hour). Cephalometric analysis showed that responders tended to be more retrognathic (sella-nasion-supramentale (S-N-B = 74.4 degrees)) than nonresponders (S-N-B = 79.3 degrees). Responders were significantly less obese (body mass index (BMI = 30.6)) than nonresponders (BMI = 37.9). There were five minor complications including minor bleeding (n = 3), prolonged odynophagia (n = 1), and minor change in taste (n = 1). There were no major complications, and no persistent difficulties with speech or swallowing. These results demonstrate that direct surgical modification of the tongue base and associated structures can significantly impact obstructive apnea. Midline glossectomy or similar procedures may be useful in a subset of patients with OSAS.

Transcription of double-stranded RNA by Escherichia coli DNA-dependent RNA polymerase. Double-stranded RNA of some virus genomes can be used as template for the DNA-dependent RNA polymerase purified from Escherichia coli. The RNA synthesis requires all four nucleoside triphosphates and manganese ions and is dependent on the presence of sigma subunit. The reaction is inhibited by rifampicin, streptolydigin and ethidium bromide, but not by DNase and actinomycin D which does not bind to double-stranded RNA. The template activity of double-stranded RNA from various viruses is different in each case. The order of template efficiency is Penicillum chrysogenum virus greater than cytoplasmic polyhedrosis virus greater than rice dwarf virus greater than reovirus. The product obtained using cytoplasmic polyhedrosis virus double-stranded RNA as template is single-stranded and hybridizes specifically to the denatured template RNA. One of the major 5'-starting nucleotide sequences of the product RNA is pppA-A-Y--. These results indicate that transcription in vitro of double-stranded RNA by E. Coli RNA polymerase is initiated at specific sites on the template.

Pharmacological characteristics of catalepsy induced by intracerebroventricular administration of histamine in mice: the importance of muscarinic step in central cholinergic neurons. Histamine-induced catalepsy was antagonized potently by scopolamine, an antimuscarinic drug, and partially blocked by sparteine. Neither methylatropine nor antinicotinic drugs could reverse histamine-induced catalepsy. These results indicate the greater importance of muscarinic receptors rather than their nicotinic counterparts in histamine-induced catalepsy. Various antiparkinson drugs, i.e. biperiden and trihexyphenidyl, which have antimuscarinic activity or dopamine agonists, i.e. L-dopa, amantadine and bromocriptine, could antagonize the histamine-induced catalepsy to various degrees. Thus, catalepsy induced by icv histamine can be evoked not only by an activation of the histamine receptor, but also indirectly due to cholinergic and dopaminergic imbalance.

AT1 angiotensin receptors mobilize intracellular calcium in a subclone of NG108-15 neuroblastoma cells. The effects of angiotensin II (AII) and related peptides on the mobilization of internal Ca2+ were studied in a subclone of NG 108-15 cells. The subclone, C1, was prepared by fluorescence-activated cell cloning using a rapid response kinetics and a large response magnitude following stimulation by AII as the selection criteria. Angiotensin I, AII, and angiotensin III (AIII) stimulated Ca2+ mobilization in the C1 cells in a concentration-dependent manner (1 nM-100 microM), yielding EC50 values of 437 +/- 80 nM (n = 4; slope = 1.6 +/- 0.3), 57 +/- 8 nM (n = 12; slope = 1.5 +/- 0.3), and 36 +/- 5 nM (n = 7; slope = 1.4 +/- 0.3), respectively. AIII was significantly more potent than AII (p less than 0.05). In contrast, Des-Phe8-AII, AII-hexapeptide (AII 3-8), and p-NH2-Phe6-AII (1-10 microM) were inactive as agonists. Although the effects of AII and AIII in C1 and parent NG108-15 cells were totally inhibited by the AT1 receptor-selective nonpeptide antagonist, DUP-753 (0.3-1 microM), the AT2-selective antagonists, EXP-655 and CGP42112A (1-10 microM), failed to block the effects of AII. DUP-753 (0.3-100 nM) produced dextral shifts of the AII-induced concentration-response curves and yielded an estimated affinity constant (pA2) of 8.5 +/- 0.2 (n = 16) using single-point analysis involving different concentrations of DUP-753. These data compared well with those obtained for the inhibition of AII-induced aortic contractions by DUP-753 (pA2 = 8.5) reported previously by others.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of lipids to the action of streptomycin on Bacillus subtilis and Escherichia coli and griseofulvin and fungizone on Aspergillus niger. An attempt was made to reveal the relation between the lipid content and components of B. subtilis and E. coli and the action of streptomycin, and those of A. niger and the action of griseofulvin and fungizone (Amphotericin B). Total lipids were extracted in CO2 atmosphere, dried, and weighed. Lipid components were analyzed by thin-layer chromatography. Complements to the growth medium of A. niger with extracted total lipids and phospholipids were made to verify the obtained results. It has been found that the action of streptomycin and griseofulvin was not correlated with lipids. On the other hand, fungizone action was manifested by the decrease in total lipids, free sterols, sterol esters, and triglycerides. Supplementation studies gave evidence of the role of total lipids and phospholipids in protecting A. niger cells against fungizone. Supplementation of 1 g of phospholipid per litre medium raised the M.I.D. of fungizone from 2.5 up to 25 microgram/ml. It was suggested to keep the fat level controlled at a minimum if it is required to increase fungizone activity.

Thrombokinetics in systemic lupus erythematosus A preliminary report. Twelve non-thrombocytopenic patients ( 3 males and 9 females) with systemic lupus erythematosus (SLE) were investigated with respect to platelet size, percentage of megathrombocytes, platelet survival and platelet production. The values for platelet size and percentage of megathrombocytes did not differ from those of a control group. In the SLE group the mean platelet MLS was identical to the control mean, and all patients with SLE had values for platelet MLS within the range of the control subjects. All SLE patients but one had values for platelet turnover within the control range. For unclear reason one single SLE patient had a moderately elevated platelet turnover value. The results of the present investigation do not support the theory that a state of compensated thrombocytolysis is present in SLE.

Quantitative and thermodynamic studies of erythrocytic ABO antigens. This paper presents recent data from quantitative and thermodynamic investigations on A and B erythrocyte antigens. In regard to weak A phenotypes on the basis of quantitative data, practically no gap is observed from the weakest Aend to the strongest A3. Weak B phenotypes give a similar distribution. However, a more precise structural analysis including kinetics and thermodynamic measurements provides convincing evidence for the heterogeneity of each type of weak B reactive structures. Weak B antigens appear to be different from one to another, but similar inside one family. However, thermodynamics failed to demonstrate a qualitative difference between the weak B antigen in BX groups and the enhanced B antigen in ABX heterozygote, phenomenon that occurs in some very rare families. The same data were obtained from kinetic and thermodynamic analysis of B reactivity in cis AB samples; it can be assumed that such mutants are all different.

Immunoreactive substance P is decreased in saliva of patients with chronic back pain syndromes. Substance P, a neuropeptide associated with pain perception, is widely distributed in the central nervous system and is decreased in the cerebrospinal fluid of chronic pain patients as compared with that of healthy human volunteers. In this study, we have demonstrated the presence of immunoreactive substance P in saliva and further, that both saliva and plasma levels of immunoreactive substance P are lower in patients with chronic low back pain than in healthy human volunteers. To our knowledge, this is the first time that substance P has been identified in human saliva. These findings, together with the noninvasive nature of saliva collection, suggest that substance P in saliva may be useful as an alternative neurochemical correlate of chronic low back pain when collection of cerebrospinal fluid and plasma samples for substance P analysis is unacceptable or inappropriate.

Changes in muscle lipid composition and resistance adaptation to temperature in the freshwater crayfish, Austropotamobius pallipes. The phospholipid and fatty acid composition of muscle lipid extracts from crayfish acclimated to 4 C and 25 C (18 hr-light photoperiod) were analyzed. The phospholipid content and class distribution, and cholesterol content were unaffected by the acclimation treatment. Unsaturation of muscle phosphoglycerides was higher in cold acclimated crayfish. Serine/inositol phosphoglycerides from cold-acclimated animals showed somewhat higher proportions of mono- and polyunsaturated fatty acids, whereas choline and ethanolamine phosphoglycerides were less affected. This was correlated with a decreased resistance of cold-acclimated crayfish to lethal high temperature. Acclimation at 4 C under an 8 hr-light photoperiod caused an increased fatty acid unsaturation of the total phospholipid fraction compared to the 4 C, 18 hr-light photoperiod acclimated animals. The resistance of 4 C acclimated crayfish to lethal high temperature, however, was unaffected by daylength treatment. The resistance of freshwater crayfish to lethal high temperature is not simply related to the degree of saturation of the muscle phospholipids. It is suggested that a breakdown in the integrity of a bulk-lipid bilayer is not involved in the process of heat death; rather, that a membrane-bound protein factor, whose thermal sensitivity is modified by changes in its phospholipid environment during temperature adaptation but not during photoperiod adaptation, is the primary site of heat injury.

Uptake and disposition of aldrin and dieldrin by isolated perfused rabbit lung. The uptake, metabolism, and release of aldrin and dieldrin by the lungs were studied by use of isolated perfused rabbit lungs that were artificially ventilated and perfused through the pulmonary artery. Both recirculating and single-pass experiments were conducted using an artificial medium as perfusate. Aldrin accumulated in the lung from the perfusate through two distinct phases of uptake: a rapid phase involving simple diffusion and nonspecific binding and a slower phase representing its metabolic turnover as dieldrin. Dieldrin was not metabolized but accumulated in the lungs by a saturable and a nonsaturable process. Single-pass experiments with aldrin indicated that the initial velocity of uptake could be fitted to one component and a constant representing the rate of metabolism. Uptake of dieldrin was biphasic: one phase independent of the perfusate concentration and the other saturable with respect to the perfusate concentration. By the application of Michaelis-Menten kinetics, the maximum amount of dieldrin accumulation attributable to the saturable component was calculated to be 0.64 mumol/lung. Our results indicate that the accumulation of these chlorinated xenobiotics takes place through the processes of simple diffusion followed by nonspecific tissue binding. There was no evidence for irreversible binding of aldrin or dieldrin, its epoxide, in the lung. While the lung plays a role in metabolizing aldrin to dieldrin followed by a transient storage, neither substrate has the potential for long-term storage in the lung.

[The effect of food intake on the content of proteolytic enzymes and gastrin in the blood of patients with peptic ulcer and chronic atrophic gastritis]. Radioimmunoassay was used to determine trypsin, pepsinogen and gastrin content in the blood serum with the use of kits produced by the firm "Oris" (France). A total of 43 patients with peptic ulcer (25 with duodenal ulcer and 18 with gastric ulcer), 20 patients with chronic gastritis and 10 normal subjects were investigated. The study was conducted on an empty stomach and after a test breakfast consisting of 2 boiled eggs, 100 g of cheese, 100 g of white bread, 25 g of butter, 50 g of sugar and 200 g of tea (57 g of proteins, 63 g of fats, 103 g of carbohydrates; calorie value comprised 1212 kcal). It has been shown that food intake is a regulator of gastrin, pepsinogen and trypsin production that permits evaluating functional possibilities of gastrin-producing cells, the main gastric cells and acinar cells of the pancreas. The investigation conducted has evidenced that compensatory shifts in the levels of gastrin, pepsinogen and trypsin taking place in gastroduodenal disease are directed to the improvement of digestive processes.

[Epidemic of cholera in Chile; 1991]. In January 1991 a severe epidemic of cholera started in Peru, a country located north of Chile. The first case in Chile was confirmed in april and so far 41 cases and 2 deaths have been reported. The epidemic is caused by Vibrio cholerae 01, El Tor biotype, Inaba serotype. Most cases occurred in Santiago, 2/3 of them in men and all above 15 years of age. An unknown number of asymptomatic infected people arriving in Santiago are the likely agents for the epidemic. Contamination of sewage and use of infected water to irrigate vegetable fields is involved in the transmission of the disease. The situation is linked to the inexistence of sewage treatment plants. In comparison to Peru, with near 200,000 patients and over 1000 deaths, the epidemic in Chile has been small as a consequence of intensive health education efforts. Personal hygiene, abstinence from eating raw vegetables and fish, destruction of presumed infected crops, and prohibition of vegetable transportation to other areas have been the cornerstone of the preventive strategies. Early treatment of severely dehydrated patients has determined a low fatality rate. At present, the epidemic is virtually controlled with 1 or 2 cases a week. However, the sanitary problems related to sewage treatment and the existence of cholera in other South American countries poses a serious problem for the future.

An ontogenetic comparison of ethanol-mediated taste aversion learning and ethanol-induced hypothermia in preweanling rats. To examine the interactive effects of ethanol (EtOH) and ambient temperature, 10-, 16-, and 20-day-old rat pups ingested pairings of sucrose solution and various doses of ethanol (intubated intragastrically) and were then exposed to relatively low or relatively high ambient temperatures. Ten- and 20-day-old pups required a higher EtOH dose than did 16-day old pups for conditioning of a sucrose aversion and for hypothermia. These age-related differences might be due to ontogenetic changes in the production and accumulation of acetaldehyde, a metabolite of EtOH. For all ages, EtOH-induced hypothermia was necessary for conditioning of the taste aversion, which is in accord with results of previous tests with adult rats (Cunningham, Hawks, & Niehus, 1988).

Work study on endodontic treatments by means of practice administration. Work analysis by means of dental practice administration is necessary for every clinical dentist. Generally speaking, endodontics sometimes may ignore the study of the operator's difficulties and/or the patient's time burden. Two dentists had treated 72 teeth on 49 patients with single visits in endodontics in one month. Vital and infected canal treatment needed almost the same working time in our clinical system. Difficult cases and work factors affect working time longer and make the standard deviation larger. Difficulties had caused incisor work to consume more time than premolar treatments. In the case of molars, clinical experience helped treatment on maxilla to be quicker than on mandible. Knack factors were to be revealed in this qualitative study.

Nomifensine and its derivatives as possible tools for studying amine uptake. An experimental antidepressive drug, nomifensine, was tested in simultaneous experiments as an inhibitor of the uptake of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) in rat brain synaptosomes. The drug was found to be a very potent inhibitor of NA (Ki 4.7 X 10(-9) M) and DA (Ki 2.6 X 10(-8) M) uptake, but relatively weak inhibitor of 5-HT uptake (Ki appr. 4 X 10(-6) M). According to kinetic studies on dopamine uptake, the inhibition was competitive. Time course studies indicated that the percentage inhibition did not increase with time. This finding suggests that inhibition of membrane uptake rather than inhibition of storage is the mechanism of action of this drug. 3 metabolites of nomifensine were also tested as inhibitors of NA and DA uptake. The addition of a 4-hydroxy group to the phenyl ring of nomifensine slightly decreased the potency, and addition of hydroxy and methoxy groups to the positions 3 and 4 in the phenyl ring, clearly decreased the potency. The structure of nomifensine is compared to that of chlorimipramine. It is suggested that the differences in selectivity as to dopamine and 5-HT uptake mechanisms might be due to 2 conformational differences: one of the phenyl rings is freely rotating in nomifensine but not in chlorimipramine, and the tertiary amine group is in a flexible side chain in chlorimipramine but rigidly tied in nomifensine.

Developmental trends in the processing of multidimensional stimuli. The ability to process variations in two dimensions of a visual stimulus as efficiently as variations in one dimension was examined in a choice--reaction-time paradigm. Kindergarten children (N = 23), second graders (N = 37), fourth graders (N = 36), and college students (N = 29) were asked to determine which of three simultaneously presented geometric stimuli was different from the other two. The number of dimensions on which the different stimulus was unlike the other two was varied. Sets of trials were also either homogeneous or heterogeneous with respect to the type of dimensional variation presented in the set. The results indicated a developmental change, which is essentially complete by ten years of age, from serial to parallel processing of dimensions.

Prevalence, awareness & treatment status of hypertension in urban population of Delhi. A community based survey for the prevalence of hypertension was carried out on a random urban sample of 13,723 adults in the age group 25-64 yr from the Union Territory of Delhi (India). Hypertension was defined as systolic pressure greater than 160 mm Hg and/or a diastolic pressure greater than 90 mm Hg or a history of current antihypertensive medication. The overall prevalence rate/1000 adults was 127.5 (116.6 in males and 136.8 in females). Mild hypertension (diastolic pressure between 91-104 mm Hg) predominated in the whole group, the proportion decreasing with increasing age in both sexes. Fifty per cent of the hypertensives were aware of their problem, the awareness being slightly higher in females (51.8% versus 46.5%). Approximately 30 per cent of the hypertensives were on medication for high blood pressure. The status control of blood pressure was low in the population, being only 9 per cent, with little difference between the two sexes. The study emphasises the enormity of the problem of hypertension in an urban population in India and poor control of blood pressure achieved in the community.

Is ubiquitin involved in the dedifferentiation of higher plant cells? Transformation of a mesophyll cell into a viable protoplast that is able to re-enter the cell cycle, divide and further differentiate into organs, is accompanied by a very rapid and important increase in ubiquitin gene expression. Three major size classes of ubiquitin mRNA transcripts were observed in protoplasts as soon as they were isolated and incubated in their culture medium. The 1.6 kb mRNAs were expressed in response to the stress caused by the isolation procedure. They decreased after a few hours of incubation in the culture medium. The 1.9 kb and the 1.3 kb mRNAs enhanced in protoplasts were also observed in young leaves and in actively dividing cells: they appeared to be developmental-stage specific. They are not expressed in response to the stress, but may be considered to be part of the dedifferentiation program induced in protoplasts. These results suggest, as the enhancement of ubiquitin gene expression coincides with the dramatic changes in gene expression observed in protoplasts, that ubiquitin may play a fundamental role in the process of cellular dedifferentiation.

Ontogeny of tracheal fluid, pulmonary surfactant, and plasma corticoids in the fetal lamb. We examined fetal plasma corticoids and flow rate, electrolyte composition, and surfactant content of tracheal fluid in chronic experiments with eight fetal lambs. From 120 to 148 days of gestation the rate of fluid production was 4.5 ml/kg per h, and there was no change in mean fluid sodium (147.8 meq/1), chloride (153.1 meq/1), calcium (2.2 mg/100 ml), and pH (6.23). Tracheal fluid potassium increased from 4.3 meq/1 at 120-130 days to 8.9 meq/1 at term, while plasma sodium, chloride, calcium, pH, and potassium were constant at 146.1 meq/1, 110.0 meq/1, 12.1 mg/100 ml, 7.39, and 4.0 meq/1, respectively. Plasma corticoids were less than 1.5 mug/100 ml total (0.3 mug/100 ml free) until 130 days, when they increased rapidly to 10.5 total (3.2 free) at 148 days. Surfactant was first detected in tracheal fluid between 124 and 133 days and its secretion increased rapidly after 135 days to a value of 125 mug/kg per h at 148 days. A sudden increase in fetal plasma corticoids does not seem to be the stimulus for appearance of surfactant in the lamb, although these hormones may induce the rapid accumulation of surfactant prior to delivery.

Long-term treatment of hypertension in the elderly with a combination of atenolol and nifedipine. The efficacy and tolerability of a once-daily, fixed combination of 50 mg atenolol and 20 mg nifedipine slow release were evaluated in a 12-month open study of 27 elderly hypertensives who were either newly presenting patients or were those who were inadequately controlled on previous monotherapy or had unacceptable side-effects with their current therapy. After 1-month's therapy with the combination, the mean sitting blood pressure 1 to 4 hours post-dose decreased from 176/103 mmHg to 146/83 mmHg and was maintained at this level for the remainder of the study. Eight patients complained of side-effects on study entry. Sixteen had complaints at some time during the 12 months of fixed combination treatment and 4 were withdrawn because of side-effects. Dizziness occurred in 6 patients on the combination but, as with side-effects overall, tended to resolve with time; its occurrence did not appear to correlate with the on-treatment blood pressure. In this group of elderly hypertension patients, therefore, the combination therapy with atenolol plus nifedipine slow release appeared to exert a greater antihypertensive effect compared with previous therapy, which included atenolol alone, with no evidence of tachyphylaxis and was reasonably well-tolerated over a 12-month period.

Interference of the IGF system as a strategy to inhibit breast cancer growth. Experimental evidence suggests that human breast cancer cells can be regulated by the IGF-I and IGF-II present in the tumor stromal elements and/or by the endogenous tumor cell IGF-II in a paracrine or autocrine fashion. Thus, blockade of the receptor signalling pathway could lead to diminished tumor growth. Blockade of the type I IGF receptor by a monoclonal antibody (alpha IR3) has been used as a strategy to demonstrate the importance of the IGF pathway. Although alpha IR3 could not block serum-free growth of breast cancer cell lines, it could inhibit anchorage independent growth in most cell lines in the presence of serum. In vivo, alpha IR3 administered at the time of tumor cell inoculation could inhibit MDA-MB-231 tumor formation in athymic mice; however, inhibition of established tumors was not seen. Moreover, alpha IR3 could not inhibit tumor formation of the MCF-7 cell line in vivo. These results suggest that blockade of the type I IGF receptor can inhibit the growth of some breast cancer cells both in vitro and in vivo. Future anti-growth factor strategies include the combination of anti-IGF receptor antibodies with IGF neutralizing modalities, the dual blockade of growth factor receptors (epidermal growth factor receptor and type I IGF receptor), and combinations of steroid hormone antagonists and anti-growth factor treatments to maximize tumor inhibition.

Arterial emboli of venous origin. In a small but significant group of patients with documented systemic emboli, a source is never determined. It is in this group of patients that an arterial embolus of venous origin should be considered. During the past 20 years, we identified four patients who fulfilled the diagnostic criteria for an arterial embolus of venous origin. In each, the diagnosis was made during life. In addition, we reviewed the 40 additional patient reports in the literature that appeared to meet the criteria for the diagnosis of venous origin arterial emboli. Noninvasive methods were useful in determining the presence of thrombus in the venous system, and right to left shunting across an intracardiac defect. We conclude that treatment with heparin is the mainstay of therapy, and that caval interruption should be used only on a selective basis.

[A proposal of a T.N.M. type of classification of the ear. O.P.A.C. classification of chronic surgical otitis]. With the advent of modern otology, cophosurgeons anxious to compare their results soon became aware of the need for a "T.N.M" type of classification for the ear. The classification described here by the authors is, in principle, a classification of the "T.N.M" type: that is, a purely descriptive classification without prognostic, pathogenetic or therapeutic pretensions. This "O.P.A.C." classification is based on a description of 4 main characteristics: 1) the existence and characteristics of potential otorrhoea, described under the letter C; 2) the characteristics of potential perforation of the tympanum, described under the letter P; 3) the appearance of the middle ear, excluding the ossicular chain, described under the letter A; 4) the condition of the ossicular chain when the surgeon has completed his exploration of the lesions, described under the letter C. Two years experience seems to have proved the convenience and usefulness of this purely clinical classification, providing otologists with a common language. While they are aware of the objections and criticisms to which it may give rise, the authors hope, on time, to improve in this classification.

Chronicity of depressive episode in relation to antidepressant-placebo response. Pooled data from three 6-week placebo-controlled, double-blind, phase III clinical trials, designed to assess the efficacy of newer antidepressants, were retrospectively analyzed to study the relationship between chronicity of presenting depressive episode and response to placebo, imipramine, and adinazolam. One hundred forty-six depressed outpatients met criteria for inclusion into this study; 80 received placebo treatment, 27 imipramine and 39 adinazolam treatment. Consistent with our hypothesis the response to placebo was low in subjects who were depressed for 1 year or longer (22.6%) as compared to a higher response rate (44.9%) among those who were not as chronically depressed. The response to imipramine and adinazolam was not related to the duration of presenting depressive episode. The implications of these findings are discussed.

Hypertrophic gastropathy resembling Ménétrier's disease in transgenic mice overexpressing transforming growth factor alpha in the stomach. Transforming growth factor alpha (TGF alpha) is thought to participate in the normal and pathologic processes of numerous tissues, including the gastric mucosa. To explore its role in vivo, transgenic mice were generated overexpressing TGF alpha in the stomach. TGF alpha induced dramatic structural and functional lesions of the glandular stomach that were similar to Ménétrier's disease in humans. Transgenic mice developed severe adenomatous hyperplasia that resulted in a striking nodular thickening or hypertrophy of the gastric mucosa. Secretions obtained from affected stomachs contained no detectable gastric acid, suggesting that parietal cell function had been greatly impaired. These findings demonstrate that overproduction of TGF alpha can stimulate cellular proliferation, suppress acid secretion, and perturb organogenesis of the stomach of transgenic mice. Moreover, TGF alpha may contribute to the pathogenesis of related human hypertrophic gastropathies, such as Ménétrier's disease.

Criminality among female alcoholics. The proband group consisted of 71 female alcoholics subjected to compulsory treatment by the Temperance Board in Malmö. 38 probands were recorded in the Penal Register. For a period from year 20 before to year 9 after the first compulsory treatment, 85 offences were committed. During the same period, less than one recorded criminal offence was expected, according to an age- and calendar year specific risk table for Swedish women. In relation to the expected incidence, the observed was not particularly high at the beginning of the period. From year 12 up to year 2 before the intervention, it increased to an extremely high level where it remained. The distribution of the crimes according to nature agreed with that valid for Swedish women in general. The average age at the crime debut was conspicuously high, about 30 years. Despite, this, the first criminal offence, as also the first gonorrhoeal infection, was an early sociomedical symptom; not until later did public assistance and conviction for drunkenness usually arise.

Infantile eczema: A long-term follow-up study. A 15-17 year follow-up study was conducted on ninety-nine patients who had suffered from infantile eczema. The persistance of the eczema and the occurrence of related conditions were noted. The persistence of eczema was shown to be greater in those patients with a positive family history of eczema and in those who had developed asthma or hay-fever. An attempt was made to see if the persistence of eczema was affected by the position of the child in the family, and some factors provoking relapses were noted. The patients were also questioned with regard to their achievements in academic examinations, and to their social, artistic and sporting activities. The results showed a success rate in examinations not significantly higher than average. It was not possible to show if there is a particular type of atopic personality. There was no constant characteristic in social or artistic patterns. The group as a whole were normal at the milestones of early development, i.e. walking, talking and reading, and also normal with regard to weight and height.

New chlorophyll-b forms in a chlorophyll-detergent photosynthetic model system. The absorption spectra of chlorophyll b in Triton X-100 micelles at room temperature are superpositions of components with absorption maxima at 640.8, 648.9, 659.5, 669.6, 682.1 and 695.7 nm, obtained from Gaussian analysis of the spectra. The last four forms strongly overlap the chlorophyll a forms of this system obtained with maxima at 659.3, 667.6, 674.3, 680.8, 686.5, 692.8, 701.9, 713.6 and 722.0 nm. Since the in vivo chlorophyll a forms practically coincide with the forms found in this system, the possible existence of in vivo overlapping chlorophyll b and a forms eventually should be taken into consideration. In this case, however, the Gaussian analysis of in vivo absorption bands in itself in the proper spectrum range cannot discriminate between chlorophyll a and b components.

Injury prior to neurectomy alters the pattern of autotomy in rats. Behavioral evidence of central neural plasticity. A common property of phantom limb pain is that a preamputation lesion continues to be felt in the same location of the phantom limb after amputation. A model of the phantom limb in the rat is provided by sectioning the sciatic and saphenous nerves. This procedure leads to self-mutilation of the denervated hindpaw, a behavior known as autotomy. There is strong evidence that autotomy is a response to painful or dysesthetic sensations referred to the anesthetic limb. The present study examined the hypothesis that the site of autotomy behavior can be altered by an injury given prior to denervation. Experiment 1 evaluated the effects of a thermal injury applied (under sodium pentobarbital anesthesia) to the medial or lateral hindpaw and digits before or after sciatic and saphenous nerve transections in order to determine whether autotomy is directed specifically to a previously injured site. The results revealed that autotomy onset occurred in the injured region of the paw in a significantly greater proportion of rats, compared to an uninjured control group, if the thermal injury had been induced before denervation: 100% of the rats with medial paw injury induced prior to neurectomy initiated autotomy in the medial digits, and 55.6% of rats with lateral paw injury initiated autotomy in the lateral digits. Rats injured after autotomy showed no such preference (medial, 33.3% and lateral, 37.5%) relative to the uninjured controls (medial, 33.3% and lateral, 17%). These results suggest that central cells, sensitized by the thermal injury, contribute to enhanced autotomy in the absence of further inputs from the injured paw.(ABSTRACT TRUNCATED AT 250 WORDS)

Smoking during pregnancy among northwest Native Americans. There is little available information on the smoking habits of Native Americans. The authors used data from the Washington State birth certificate to determine the prevalence of smoking during pregnancy among Native American mothers in Washington State. From 1984 through 1988, 39.8 percent of all Native Americans smoked during their pregnancy. Smoking patterns during pregnancy differed markedly between Native Americans and whites according to maternal age and marital status. The smoking prevalence in Native Americans, adjusted for maternal age and marital status, was 1.3 times higher than that found in Washington State white women. This is the first analysis of statewide smoking rates during pregnancy among Native Americans. The birth certificate can serve as a readily accessible and low cost surveillance system for populations such as Native Americans, who are otherwise difficult to study. Smoking intervention programs need to be targeted at Native Americans, and how their smoking patterns differ from those of the general population needs to be recognized.

Heterogeneity of autoantibodies against thyroid peroxidase in autoimmune thyroid disease: evidence against antibodies directly inhibiting peroxidase activity as regulatory factors in thyroid hormone metabolism. The close relationship between thyroid microsomal antigen and thyroid peroxidase (TPO) is now well established. The present study evaluates the significance of autoantibodies against TPO (anti-TPO-Abs) in the various forms and stages of autoimmune thyroid disease with respect to a possible heterogeneous nature and particularly to their influence on TPO activity. When measured by a RIA using purified human TPO, anti-TPO-Abs were highly correlated with microsomal antibodies determined by enyzme-linked immunosorbant assay (r = 0.96; P less than 0.0001) and with the results of a TPO immunoprecipitation assay using crude microsomal preparations (r = 0.76; P less than 0.001). Relating the results of these assays to the reactivities of patients' sera with thyroid microsomes in immunoblot under nonreducing and reducing conditions, discordant results could be observed in a few cases. Further analysis of these data indicate a heterogeneous nature of anti-TPO-Abs, which react with at least two antigenic domains of the TPO molecule. The comparative analysis of patients with hyperthyroid Graves' disease, patients with Graves' disease in clinical remission, and patients with hypothyroid Hashimoto's thyroiditis revealed no significant differences in the antibody spectrum. When evaluating the direct influence of anti-TPO-Abs on the activity of TPO under a rigorous methodological approach, we found no significant inhibition of the enzymatic activity by any of the sera investigated from patients with autoimmune thyroid disease compared to that in sera from normal controls. In conclusion, the data indicate a heterogeneous nature of anti-TPO-Abs. The spectrum of antigenic epitopes recognized by anti-TPO-Abs seems not to be significantly different in the various forms and stages of autoimmune thyroid disease. The lack of an inhibitory effect of autoantibodies on TPO activity argues against direct binding of autoantibodies to the enzymatic sites of TPO and indicates that they are not important factors in producing thyroid dysfunction in autoimmune thyroid disease.

[Effects of plant protective agents and pesticides on the processibility of milk with special consideration to microbiological technology]. The authors studied the effects of the active ingredients contained in 43 pesticides and insecticides on dairy cultures and the suitability of milk contaminated in vitro with selected organophosphorus insecticides. The acid-forming property of yoghurt, kefir, butter and cheese cultures, the clotting property of milk and the ripening process of Camembert were used as testing criteria. The herbicides 2-methyl-4,6-dinitrophenol (DNOC), 2,4, 5-trichlorophenol, 2-methyl-4-chlorophenoxyacetic acid (MCPA), 4-(2-methyl-4-chlorophenoxy) butyric acid (MPCB), 2,4-dichlorophenoxyacetic acid (2,4-D), 2,2-dichloropropionic acid (dalapon), the chlorinated insecticide heptachlorepoxide and the fungicide pentachlorophenol exerted inhibitory effects when applied at concentrations of more than 100 p.p.m., whereas most of the organophosphorus and chlorinated insecticides under investigation produced no detectable effects on the culture activity when used at concentrations up to 100 mg/kg. The clotting property of milk was not impaired by the pesticides and insecticides at concentrations up to 100 mg/kg; the same was true of the ripening process of Camembert.

A serological investigation into the acidic alpha-D-mannosidase in normal Angus cattle and in a calf with mannosidosis. Antiserum was raised in a rabbit against bovine kidney acidic alpha-mannosidase that had been purified 570-fold by affinity chromatography on concanavalin A--Sepharose and Sepharose 4B-xi-aminohexanoylmannosylamine. The antiserum precipitated the acidic but not the neutral alpha-mannosidase in normal calf tissues. Human acidic alpha-mannosidase cross-reacted partially with the antiserum, emphasizing the close structural resemblance between the enzyme in the two species. The residual acidic alpha-mannosidase in the tissues of a calf with mannosidosis was also precipitated by the antiserum, the same volume of antiserum being required to precipitate a unit of alpha-mannosidase activity from the normal and pathological tissues. The concentration of cross-reacting material detected by antibody-consumption experiments in the organs of the calf with mannosidosis appeared to be proportional to the concentration of the residual acidic alpha-mannosidase. It is suggested that the residual acidic alpha-mannosidase in mannosidosis accounts for the cross-reacting material detected and that it is unlikely that enzymically inactive but cross-reacting material is present. The residual acidic alpha-mannosidase could be a decreased concentration of the normal gene product or an altered enzyme with a decreased specific enzymic activity and a correspondingly decreased antigenicity.

Treatment of experimental Escherichia coli pyelonephritis in rat by ciprofloxacin in comparison with tobramycin. The ciprofloxacin efficacy was compared to that of tobramycin in an Escherichia coli pyelonephritis model in rat. Treatments started 48 h after ligation of the left ureter and inoculation of the bladder and continued for 5 days. Ciprofloxacin (2.5 mg/kg/d and 10 mg/kg/d) was administered intravenously either in a single daily dose or in 2 divided doses at 12 h intervals. Tobramycin (2.5 mg/kg/d and 10 mg/kg/d) was administered by the intramuscular route, in a single daily dose. Ciprofloxacin 10 mg/kg/d was as efficacious as tobramycin irrespective of dosage schedule. Ciprofloxacin 2.5 mg/kg/d was more effective when given twice a day than once.

[The neuronal mechanisms of the defensive reaction to stimulation of the cutaneous nerve in the freshwater snail]. The whole body withdrawal reaction of freshwater snail Planorbarius corneus consists of two phases. In the first phase the shell is rapidly moved down to cover the head, in the second one the body is slowly retracted into the shell. The columellar muscle is involved in this behaviour. Motoneurons of the columellar muscle are identified in the cerebral, parietal and pedal ganglia. In the preparation of the central nervous system connected with the columellar muscle it is demonstrated that stimulation of the lip nerve evoked a biphasic motoneuron excitation responsible for two phases of the muscle contraction. A similar biphasic excitation of the motoneurons could arise spontaneously. This implies that the whole body withdrawal reaction is, at least partly, a fixed act generated by a central mechanism (a central program) which is triggered by a sensory stimulus. The central mechanism of the withdrawal reaction could be also activated by a depolarization of some columellar motoneurons. This suggests that the central mechanism received a feedback from the motoneurons.

A two year follow up of new long-stay patients in an inner city district general hospital. In 1967 Magnus described 'the new chronics', patients admitted to a psychiatric hospital who then stayed for more than one year. Since that time many studies have examined this patient group but the majority have focussed on psychiatric hospital populations. There is some doubt, however, as to whether the characteristics of new-long stay patients in District General Hospital (DGH) psychiatric in-patient units are comparable. The current paper describes a two year follow-up study of Medium and New-Long Stay patients identified within an inner-city DGH unit in 1986. Elderly patients with affective disorders and patients with organic brain syndromes were particularly highly represented. Length of stay at the time of the original survey, male sex, associated physical disability, and the presence of a secondary diagnosis were particularly associated with poor outcome. The results are discussed in relation to service provision.

Human tilt perception in a dynamic environment. This study examines the perception of tilt and linear acceleration as sensed through the utricular otolith of the vestibular system. Any sensation derived from the otolith is a consequence of the displacement of the otolith parallel to its own plane. This leads, naturally, to the definition of a sensation plane. A model is presented which defines this sensation plane. It assumes that the sacular otolith contribution is negligible, an assumption substantiated by correlation with experimental data by Schöne. Applying this model to perceived pitch angle, a simple equation is presented which relates the number of Gs and actual pitch angle to the perceived pitch angle. Experimental data are needed to develop perceived sensation curves for the sensation plane. The model implies that a state of confusion exists outside the realm of our prior experiences. Disorientation or motion sickness may be related to this confused state. In addition, new avenues of inquiry are introduced.

Incomplete membranous obstruction of the inferior vena cava. Hemodynamic measurements and correction by balloon membranotomy and surgical resection. This report discusses a patient with chronic liver disease and portal hypertension, initially thought to be caused by chronic bile duct obstruction or chronic hepatitis B. For evaluation of portal hypertension, hepatic vein catheterization was performed, disclosing incomplete membranous obstruction of the inferior vena cava at the level of the diaphragm--the probable cause of the liver disease. The obstruction was corrected by balloon membranotomy and surgical resection of the membrane. Hepatic vein catheterization in patients with chronic liver disease and portal hypertension allows detection of this lesion as well as evaluation of hepatic and portal hemodynamics.

Carboxyhaemoglobin dissociation in the cadaver following attempted resuscitation. A series of 300 cases of fatal carbon-monoxide poisoning showed wide variations in carboxyhaemoglobin saturation. Levels below 50% in 24 subjects under the age of 70 were probably falsely low following attempted resuscitation on the way to hospital. Artificial respiration, especially with oxygen-rich gas, causes dissociation of carboxyhaemoglobin in the lungs of the cadaver while movement of blood into and out of the lungs, with mixing, lowers the saturation levels in the neighbouring large veins. In four cases subclavian blood showed saturation levels much lower than blood from sites further from the lungs. Blood should be taken from the femoral vein to get true readings.

Neuroglial relationship in experimental central demyelination in rabbits. Experimental allergic encephalomyelitis (EAE) induced in the rabbit, initially showed inflammatory lesions, followed by demyelination. The EAE lesions also exhibited an ascendency in their appearance, i.e. they involved the spinal cord, brain stem and cerebellum in that order. During the inflammatory stage of EAE, the astrocytes became hypertrophied and the oligodendrocytes were seen to be degenerating. The inflammatory cells included lymphocytes, plasma cells, and gitter cells. When demyelination had set in, there appeared a paucity of oligodendrocytes and a marked astrocytosis in and around the lesions. The relationship of the oligodendrocytes with the maintenance of myelin in the central nervous system is discussed.

Clinical presentations and mechanisms of necrotizing angitis of the skin. Cutaneous necrotizing angiitis may be present as either palpable purpura or less commonly as recurrent urticaria, and each clinical presentation may be associated with hypocomplementemia or a normal complement system. A variety of mechanisms may be operative in the production of necrotic vascular skin lesions that appear as similar, recognizable morphologic lesions. These mechanisms include immune complexes, cellular-type hypersensitivity reactions, and initiation or modulation by mast cells. Two cellular patterns have been recognized in the skin of patients with cutaneous necrotizing angiitis that can be correlated with the involvement of the complement system in serum. In patients with hypocomplementemia, there is an infiltrate of neutrophils that is consistent with a process involving immune complexes; in patients with normocomplementemia there are lymphocytes and activated lymphocytes consistent with participation in part by cellular mechanisms. In both the hypocomplementemic and normocomplementemic forms and as well as in a unique patient in whom the mast cell may initiate the venular damage, the mast cell, which its content of chemical mediators, has the capacity to initiate as well as modulate subacute and chronic vascular damage.

Persistence of increased nonspecific bronchial reactivity in allergic children and adolescents. Nonspecific bronchial reactivity (BR) is commonly associated with asthma. It can be found, however, in subjects with allergic rhinitis. Studies have not been done looking at changes in nonspecific BR in allergic children over time. Therefore, we report on our longitudinal study of BR in allergic children and adolescents. The reported subjects are part of a larger ongoing study in a selected population of families with asthma and of twins. Initiated in 1972, the subjects reported in this study are subjects who have had at least one follow-up visit through 1989 and did not have asthma, but had allergic histories at either their initial visit or follow-up visits. Subjects completed a questionnaire, had skin tests, determination of a serum IgE level, and a determination of nonspecific BR with a methacholine challenge. Subjects were 6 years of age or older or 21 years of age or younger at initial visit. Subjects from families with asthma (N = 76; mean age, 12.09 years; +/- 4.6 SD) and twins (N = 36; mean age, 11.81 years; +/- 3.81 SD) were followed longitudinally, and their age at follow-up visits was not restricted. In this study we observed that, of 106 subjects, 66% initially demonstrated nonspecific BR. At their first and second follow-up visits, 70.4% and 61.3% demonstrated persistence of their BR. These data demonstrate that allergic children and adolescents have increased nonspecific BR. There was not a significant loss of BR over time in the studied subjects.

Medication compliance and serum lipid changes in the Helsinki Heart Study. 1. To control the bias caused by poor medication compliance in the Helsinki Heart Study three methods were used to measure medication compliance during the total 5 years follow up time: continuous capsule counting, semi-annual urine gemfibrozil analysis and a new method, the digoxin marker at the end of the third and fifth study years. 2. The serum lipid responses to gemfibrozil treatment varied linearly with the level of medication compliance, e.g. the mean change in serum total cholesterol was -11.4% among those whose apparent capsule consumption was greater than or equal to 90% of the scheduled dosage, -11.2% among those who had greater than or equal to 90% positive gemfibrozil analyses and -11.4% among those with good compliance according to both digoxin marker measurements. In contrast the mean serum cholesterol change was only -0.02% if the mean daily capsule count was less than 50%, -1.7% with fewer than 50% positive gemfibrozil analyses and -1.1% if the result was poor in both digoxin marker measurements. 3. Combining the different method findings revealed that the cholesterol changes tended to be small in those groups who had poor compliance classification measured by any of the methods, even if the other results showed good compliance.

Biological factors affecting concentrations of serum LpAI lipoprotein particles in serum, and determination of reference limits. We used an electroimmunoassay to measure LpAI lipoprotein particles (lipoproteins containing apolipoprotein AI but not apolipoprotein AII) in serum of a presumably healthy population of about 1000 subjects, noting sex- and age-related variations for the age interval four to 70 years. Results were higher for women than men. For males, the value for the 50th percentile of the distribution was highest in the 10- to 14-year subgroup, 0.69 g/L, decreasing to 0.60 g/L in adults. For females, the values increased regularly, from 0.59 g/L at ages four to 10 years to 0.79 g/L after age 55 years. The influence of puberty, menopause, oral contraceptives, alcohol consumption, and morphometric characteristics was studied. Only being overweight by more than 20% statistically influenced LpAI values in men and in women. We used these results to select a reference population and to establish reference limits of LpAI at ages 25 to 35 years: 0.40-0.95 g/L for men and 0.46-1.05 g/L for women.

Population genetics of hypervariable loci: analysis of PCR based VNTR polymorphism within a population. Using a polymerase chain reaction (PCR) based method, genotypes at two hypervariable loci (3' to the Apo-B-structural gene and at the ApoC-II gene) were determined by size classification of alleles. Genotype data at the Apo-B locus (Apo-B VNTR) were obtained on 240 French Caucasians; the sample size for the ApoC-II VNTR was 162. For 160 individuals two-locus genotype data were available. Applications of some recently developed statistical methods to these data indicate that both of these loci are at Hardy-Weinberg equilibrium (HWE) and there is no indication of allelic associations between these two unlinked loci. In addition, the observed numbers of alleles (12 for the Apo-B and 11 for the ApoC-II VNTR loci) are also consistent with their respective expectations based on the observed heterozygosities (76.9% for the Apo-B and 85.9% for the ApoC-II loci) suggesting genetic homogeneity of this population-based sample. The multimodal distribution of allele sizes observed for both loci indicate that the production of new alleles at such VNTR loci may be caused by more than one molecular mechanism. The utility of such highly polymorphic loci for human genetic research and forensic applications are discussed in the context of these findings.

Comparison of chromosome breakages in lymphocytes and fibroblasts from control women and women taking oral contraceptives. To determine whether exposure to synthetic hormones resulted in increased chromosome damage in cells other than lymphocytes, we evaluated series of lymphocyte and fibroblast cultures from five control women and five women taking oral contraceptives (OC). The results of this study showed: (1) no difference in chromosome breakages between lymphocytes and fibroblasts; (2) no differences in breakages in replicate fibroblast cultures exposed to fetal calf serum, autologous serum, homologous serum, or homologous serum from OC users; (3) no difference in breakage between lymphocyte and fibroblast cultures from OC users, compared with lymphocyte and fibroblast cultures from control women; and (4) no increase in the frequency of cytogenetically aberrant stem-lines in fibroblast cultures from women taking OC. These findings suggest that synthetic hormones do not cause increased chromosome breakages in fibroblasts from women taking OC.

Rapid induction of c-fos transcription reveals quantitative linkage of RNA polymerase II and DNA topoisomerase I enzyme activities. The functional association between DNA topoisomerase I and gene activity has been analyzed using the tightly regulated c-fos proto-oncogene, which undergoes rapid transitions between active and inactive states of transcription. We show that the topoisomerase I inhibitor camptothecin can be used to measure topoisomerase I activity throughout the transcription cycle of the c-fos gene. Upon induction of c-fos transcription in the presence of camptothecin, topoisomerase I cleavages spread through the gene in the 5' to 3' direction and concomitantly transcriptional elongation is retarded. Parallel kinetic measurements of RNA polymerase II activity and topoisomerase I activity demonstrate a quantitative and temporal link between the two enzymes. Our results argue that topoisomerase I quantitatively relieves the torsional consequences of transcriptional elongation in intact cells.

Quantitative anatomy of the lungs of the red-eared turtle, Pseudemys scripta elegans. Morphometric and sterological methods were employed to evaluate the anatomical gas-exchange potential of the lungs of the fresh-water turtle, Pseudemys scripta elegans. The total lung volume and lung wet weight increase with the 1.4 power of body weight. Right and left lungs are similar in size and shape, containing a tissue-free central lumen, which occupies 55 per cent of the maximally inflated lung. The remainder is parenchyma, composed of 90 per cent air and 10 per cent tissue, with an effective surface-to-volume ratio of 18 cm-1. The anatomical diffusion factor (ADF), or the ratio of respiratory surface area to mean diffusion distance in lung tissue, is 1 order of magnitude lower than in the mammalian lung. Taking interspecific differences in O2 consumption into account, the degree to which the lungs are exploited, deltaPtO2, is similar in Pseudemys and in mammals at basal, resting and exercising states.

Recurrent miscarriage--outcome after supportive care in early pregnancy. One hundred and thirty three couples were investigated at a recurrent miscarriage clinic. In their next pregnancy 42 women (Group 1) with unexplained recurrent miscarriage were managed with a programme of formal emotional support and close supervision at an early pregnancy clinic. Two women were seen in 2 pregnancies (44 supervised pregnancies); 86% (38 of 44) of these pregnancies were successful. Four of the 6 miscarriages had an identifiable causal factor. Nine women (Group 2), also with unexplained recurrent miscarriage, acted as a control group. After initial investigation they were reassured and returned to the care of their family practitioner and did not receive formal supportive care in their subsequent pregnancy; 33% (3 of 9) of these pregnancies were successful (p = 0.005; Fishers Exact Test). Whilst acknowledging that there is a significant spontaneous cure rate in this condition, emotional support seems to be important in the prevention of unexplained recurrent miscarriage, giving results as good as any currently accepted therapy.

Mooren's ulcer and evidence of stromal graft rejection after penetrating keratoplasty. A Mooren's ulcer developed in a 6-year-old girl after a penetrating keratoplasty for Peters' anomaly. A destructive, circumferential, and centripetal stromal ulceration recurred despite conjunctival resection, corneal gluing, topical and systemic administration of corticosteroids, and repeat graftings. Results of a systemic and a rheumatologic examination were unremarkable. Histopathologic evaluations of donor grafts consistently disclosed a lymphocytic and a plasma cell infiltrate. Indirect immunofluorescent staining using a normal donor cornea substrate was positive at the level of Bowman's membrane and stroma. The patient's lymphocytes were stimulated by a partially purified bovine corneal antigen and a positive antibody titer was found in the patient's sera to the same corneal antigen. These results suggest humoral and cell-mediated immune mechanisms can be involved in the initiation and perpetuation of a stromal rejection process after penetrating keratoplasty.

Cyclical changes of vaginal cytology in the cat. Vaginal smears from seven cats were examined at two-day intervals for 32 days in order to describe the cyclical pattern of epithelial cells exfoliated throughout the stages of the estrus cycle. Vaginal epithelial cells were classified as parabasal, intermediate and superficial (nucleate and anucleate) cells, and their dimensions were measured for the purpose of definition. The percentages of the epithelial cell populations (i.e. Maturation Index) from Wright's stained smears, were determined at all stages of the estrus cycle. The Eosinophilic Index was estimated on Papanicolaou stained smears. Smears of cats in estrus were populated almost entirely with nucleate and anucleate superficial epithelial cells. Proestrus was characterized by intermediate epithelial cells with increasing eosinophilia, and rare neutrophils. Metestrus was associated with desquamation of intermediate and parabasal epithelial cells, neutrophils and debris. In the anestrus period, groups of intermediate cells and some parabasal epithelial cells were exfoliated. Two cats in the study did not cycle and exhibited anestrus. Of the five cats cycling, eight estrus periods were observed of two to five days duration. The cycles were of 15 to 17 days interval in three normal cats. Two cats did not show a second estrus within 30 days, and were subsequently found to have bacterial growth on the culture of vaginal swabs, however the presence of an initial ovular estrus cannot be ruled out. The rare presence of erythrocytes was associated with vaginal bacterial infections and discharge in two cats.

Distinct stimulatory effect of platelet-activating factor on prostaglandin I2 and thromboxane A2 biosynthesis by rat dental pulp. Platelet-activating factor (PAF-acether), but not lyso PAF, stimulated the production of both PGI2 and TXA2 by rat dental pulp tissue in vitro. However, there were differences in the dose- and time-dependence of the stimulatory effects. PAF-acether antagonists, Bn 52021, CV 3988 and kadsurenone, dose dependently inhibited PAF-acether-induced PG production. BN 52021, CV 3988 also dose dependently inhibited TX production, but kadsurenone was almost without effect on TX production. Pretreatment of the tissues with PAF-acether or phorbol 12-myristate 13-acetate completely abolished the effect of the second challenge with PAF-acether. The stimulatory effects of PAF-acether and the calcium ionophore A23187 on PGI2 production were completely blocked by removal of extracellular calcium, whereas the effects on TXA2 production were not. TMB-8, an intracellular calcium antagonist, completely inhibited PAF-acether-induced PG production, whereas it slightly inhibited TX production. H-7, a protein kinase C inhibitor, and neomycin, a phospholipase C inhibitor, completely inhibited PAF-acether-induced PG and TX production, whereas W-7, a calmodulin inhibitor, did not. These results suggest that PAF-acether stimulates PGI2 and TXA2 production in rat dental pulp by interacting with distinct PAF-acether receptors, and that these receptors are coupled to independent signal transduction pathways which have a different dependence on extra- and intracellular calcium.

Peripheral neuropathy in systemic lupus erythematosus. We studied 33 consecutive patients with systemic lupus erythematosus (SLE) for neuropathy by employing the Neuropathy Symptom Score (NSS), Neurological Disability Score (NDS), EMG and nerve conduction velocity (NCV) studies, and determinations of vibration thresholds (VT). Polyneuropathy defined as NCV abnormalities of two or more nerves occurred in seven patients (21%). Neuropathic symptoms showed a poor correlation with NCV and VT, while clinical neuropathic signs, VT, and NCV correlated with each other in most instances. When reporting frequencies of neuropathy in SLE, NCV studies should be used as a basis. NSS, NDS, and VT give additional quantifiable information and can be useful in the follow-up of patients and for evaluating the response to therapy.

Effects of flutropium on experimental models of drug- and allergy-induced rhinitis in guinea pigs. The effects of flutropium on histamine (Hist)-induced increase in intranasal pressure in non-sensitized guinea pigs and nasal mucosa capillary permeability in passively sensitized guinea pigs were investigated. Flutropium (0.3%), atropine (0.3%), diphenhydramine (0.01%) and cimetidine (0.1%) were directly inhaled into the nasal cavities by an ultrasonic nebulizer for 20 min, followed by inhalation of Hist (0.1%) for 10 min. Flutropium, atropine and diphenhydramine had an inhibitory action on the Hist-induced increase in intranasal pressure in guinea pigs. Cimetidine had no effect on this system. In passively sensitized guinea pigs (the challenge was performed 48 hr after sensitization), a 0.1-1.0 mg/kg injection of flutropium (i.v.) dose-dependently inhibited the allergic nasal mucosa capillary permeability. Atropine (10 mg/kg, i.v.) had no inhibitory action on this system. These results suggest that inhalation into the nasal cavities and i.v. injection of flutropium are effective in experimental models of drug- and allergy-induced rhinitis of the guinea pig.

[Use of serologic reactions for determining the concentration of the determinants of an antigen and its valence]. By the serological tests with the erythrocytic diagnostic agents it is possible to estimate the concentration of the determinants in the antigenic preparation under study. For this purpose it is necessary to have at one's disposal the data on the molecular weight and concentration of the reference antigen, valence of erythrocytes loaded with the antigen or antibodies, and antibody heterogeneity index. If these values are known, then one can calculate the concentration of antigenic determinants in terms divided by the valence of the reference antigen. With the aid of pure antibodies preparation obtained with the immunosorption procedure it is possible to measure the determinant concentration of the antigen tested and the valence of the reference antigen. For the capsular antigen of plaque bacilli the valence was estimated by two independent methods and in both cases it was close to 10. The valence of the reference capsular antigen permits to calculate the concentration of the antibody molecules in the hyperimmune sera without isolation of pure antibodies.

Effect of cortisol on human fetal lung in organ culture: a biochemical, electron-microscopic and autoradiographic study. Human fetal lung tissue obtained during the second trimester was cultured as organ culture with or without cortisol. The effect of cortisol on the phospholipid metabolism, as related to the appearance of osmiophilic lamellar bodies and the localisation of newly incorporated choline, was studied. In cortisol-treated explants, the concentration of saturated lecithins and the incorporation of (Me-3H)-choline into saturated lecithins increases significantly concomitantly with an increased number of osmiophilic lamellar bodies. The labelled choline is predominantly associated with these bodies. The obtained results indicate that cortisol accelerates the synthesis of pulmonary surfactant in the human fetal lung as early as in the second trimester.

Minimal biliary excretion and enterohepatic recirculation of lormetazepam in man as investigated by a new nasobiliary drainage technique. The pharmacokinetics of lormetazepam (LMA) was studied in five patients with intact and interrupted enterohepatic recirculation (EHR) after an oral dose of 0.03 mg/kg given as solution. The disposition of lormetazepam in plasma was characterized by peak plasma levels of 14-60 ng/ml after 20-40 min. Peak plasma levels of the unchanged drug were higher (p less than 0.05) in case of interrupted EHR as compared to intact EHR. The areas and the plasma levels vs time curves of lormetazepam and its glucuronide were not statistically different and the oral clearance of lormetazepam was similar in both parts of the study (median 3.1 and 3.6 ml/min/kg). In case of interrupted EHR, 23-58% of dose was excreted as lormetazepam and its glucuronide with the urine during 24 h, in case of intact EHR, the urinary dose fraction was 9-35% (p less than 0.05). The 24 h postdose-bile fraction contained only 0.3-2.8% of the oral lormetazepam dose in form of the drug and its glucuronide. In conclusion, only negligible amounts of lormetazepam are excreted in bile. The demethylated metabolite lorazepam was not detectable in the biological samples investigated.

Effect of age upon the thyroid gland and pituitary thyrotrophs of the rat. Male and female rats ranging in age from birth to 26 months, were used to study age changes in the rat thyroid and pituitary thyrotrophs. The thyroid follicular cells were cuboidal in shape until 10 mo. of age. Between 10-15 mo. the follicular cells became columnar in shape and contained intracellular colloid droplets. After 15 mo. the gland appeared mixed and consisted of both dilated follicles lined with flattened epithelium and hyperplastic follicles. The pituitary thyrotrophs were not demonstrable at birth but were visible at weaning. The size of the thyrotrophs correlated with the morphological status of the thyroid. Cytoplasmic vacuoles were first evident at 10 mo. and became more prominent as age progressed. The presence of large vacuolated thyrotrophs appeared to be related to the senile hyperplastic thyroid. No sex differences were noted.

Recovery of a Sendai virus variant with temperature-sensitive hemolytic activity from persistently infected cells from mouse brain. A persistently infected cell line designated MB/Senas was established by cultivation of mouse brain cells from four-day-old C3H mice infected intracerebrally at birth with 10(6) PFU of Sendai virus, strain 52. After 5 passages, 0.16 per cent of Sendai52 antiserum (containing two 50 per cent plaque reducing doses/ml of serum) was introduced into the culture medium. The addition of antiserum was accompanied by a rise in cell-associated viral antigen from a level of 5 per cent antigen positive cells to 100 per cent demonstrable by both intracellular and membrane immunofluorescence. A variant of Sendai52 virus, designated Sendaias, was recovered from MB/Senas by inoculation of supernatant medium into chick embryos. Infection of chick embryos at 37 degrees C was abortive. Fifty per cent or less of chick embryos infected at dilutions 10(-1) to 10(-9) yielded detectable virus. Hemagglutination (HA) was weak but could be improved by trypsinization of allantoic fluids. Neuraminidase (NA) activity was barely detectable. Hemolysis (HE) was absent. Propagation of Sendaias virus at 33 degrees C showed no change from weak HA and NA activities but HE activity was now apparent which was temperature sensitive. Mortality of infected chick embryos increased to 100 per cent. HE activity and lethality for chick embryos was thermolabile at 45 degrees C.

Total body haemoglobin estimated with the alveolar CO method as compared with a 51Cr technique. Total body haemoglobin was estimated by the alveolar equilibrium CO method and by dilution of 51Cr-tagged erythrocytes in 22 patients with a wide range of haemoglobin concentrations (51-190 g/l). The resulting regression equation: THBCO =47 + 0.81 X THbCr, where THn is expressed in grams, shows that with increasing THb successively lower values were obtained with the THbCO method as compared with the THbCr method. Individual values were calculated for the M-factor, i.e. the ratio of the haemoglobin affinities to O2 and CO. These values were positively and significantly correlated to the red-cell content of 2.3-diphosphoglycerate. The findings are consistent with a recent hypothesis that the effect of 2.3-DPG on CO affinity may not be equivalent to its effect on oxygen affinity. The discrepancy between the two methods of estimating THb may therefore be apparent only and due to a systematic variation in the M-factor.

Oncofetal antigen expression in head and neck carcinoma. Oncofetal antigens (OFA) are proteins expressed during periods of embryonal/fetal development and on malignant cells. Previous investigations detected the presence of phase-specific 44- and 200-kd OFA, using a monoclonal antibody (MoAb 115). This study will determine if primary head and neck squamous cell carcinomas express the 44-kd OFA, and will assess the possible role of OFA in oncogenesis. Fifteen primary human head and neck squamous cell carcinomas (HNSCC) and six HNSCC cell lines were tested for OFA expression. Thirteen primary cancers and three cell lines demonstrated various degrees of OFA positivity. Oncofetal antigens are proposed to represent a proto-oncogene active during fetal development and malignant growth in head and neck squamous cell carcinomas.

Intracellular ATP mimics GTP-gamma-S in generating Ca2+ oscillations in pancreatic beta-cells. Intracellular free calcium ([Ca2+]i) was measured in individual pancreatic beta-cells from mice using dual emission microfluorometry and the indicator Indo-1 applied by a patch clamp pipette. GTP-gamma-S (100 microM) injected together with 0.3 or 3 mM ATP evoked repetitive [Ca2+]i transients with a frequency of about 1 per min in beta-cells kept at a membrane potential of -70 mV. The oscillatory pattern was unaffected by the Ca2+ channel blocker verapamil (50 microM). When omitting GTP-gamma-S from the pipette medium it became evident that 3 mM ATP alone can induce oscillations. The results provide additional evidence for an important role of ATP in the ionic control of insulin release, indicating that such regulation may also involve activation of G-proteins.

Role of carbonate in acid neutralization of aluminum hydroxide gel. The role of carbonate in the acid neutralization of a carbonate-containing aluminum hydroxide gel was studied. The pH-stat neutralization reaction was comprised of three phases: an initial, immediately reacting phase; a slow, zero-order phase; and a terminal, fast zero-order phase. The evolution of carbon dioxide and the appearance of aluminum ions were monitored during neutralization. Acid neutralization is believed to occur predominantly at the aluminum-carbonate bond during the slow phase of neutralization. The reaction of structural carbonate disrupts the gel structure and increases the porosity and surface area of the gel. The diffusion of acid into the gel structure is facilitated and accelerates the neutralization rate, as seen in the final phase of the pH-stat titrigrams. The behavior of carbonate is probably responsible for the rapid and complete neutralization of acid generally observed with carbonate-containing aluminum hydroxide gel.

Phage typing scheme for group D streptococci isolated from human urogenital tract. Streptococci of Lancefield group D were isolated from 52.2% of pharyngeal, 55.5% of urethral, 56.6% of endocervical, and 75.4% of ano-rectal specimens. Seventeen phages isolated from sewage and urogenital specimens were selected for phage typing. Four of these lysed only the strains of Streptococcus faecalis and its variety liquefaciens. Another six phages lysed only the strains of Streptococcus faecium and its variety durans. With the help of seven bacteriophages, 346 of 384 (90.1%) strains of S. faecalis and its variety liquefaciens could be classified into 27 types. Similarly, with the help of 10 other bacteriophages, 97 of 117 (82.9%) strains of S. faecium and its variety durans could be grouped into 22 types. In 72 of 87 (82.7%) cases, similar phage types were obtained at different culture sites of the same individual.

Food contains the bioactive peptide, cyclo(His-Pro). Cyclo(His-Pro) (CHP) is a cyclic dipeptide with numerous biological activities. As small di- and tripeptides may be absorbed intact when ingested orally, we were interested in examining several common foods for the presence of cyclo(His-Pro)-like immunoreactivity (CHP-LI). In all foods tested, CHP-LI was found at levels 5-1500 times those previously found in human plasma. This CHP-LI was identical to authentic CHP by immunoidentity and chromatographic behavior. We conclude that 1) CHP-LI is readily detectable in several common food sources; 2) this CHP-LI is indistinguishable from authentic CHP; and 3) it is likely the CHP-LI in foods is absorbed in quantities sufficient to cause elevations of CHP-LI in plasma to biologically significant levels.

Morphologic and electrophysiologic effects of cochlear implantation and electrical stimulation. The nondeafened guinea pig model was utilized in this study to assess the functional and morphologic effects of cochlear implantation and electrical stimulation. Auditory brainstem responses (ABRs) were recorded prior to and following intrascalar implantation of a 3M-House cochlear electrode (n = 41 ears), as well as after electrical stimulation (n = 23 ears). The experimental population was divided into the following groups according to implantation and stimulation parameters: 200 microA for 3 hours (group I); 200 microA for 24 hours (group II); 400 microA for 3 hours (group III); implanted, but not stimulated (group IV); and nonimplanted, not stimulated ears (group V). Of those cochleae that sustained the trauma of implantation, 32 percent had no detectable ABR to 110 dB SPL clicks, while only 7 percent additionally failed to respond to 130 dB SPL clicks. No significant difference (one-way ANOVA with repeated measures at the 95 percent confidence limit) could be detected when comparing those ears that retained ABRs according to experimental grouping. Morphologic analysis was performed on 29 cochleae. Spiral ganglion "packing densities" were not found to be significantly different among the groups (ANOVA). The status of the organ of Corti was significantly better in groups II and V in comparison to the other groups (Kruskal-Wallis test with pairwise comparisons, p less than 0.05); there was no discernible dose-response relationship. Morphologic and electrophysiologic changes correlated with insertion trauma and infection rather than with electrical stimulation at the levels tested in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothyroidism and the ear: electrophysiological, morphological, and chemical considerations. There is both clinical and laboratory evidence that hearing loss can result from congenital and acquired hypothyroidism. The reversibility of this process, however, and its incidence and pathophysiology are not universally agreed upon. Laboratory animals rendered hypothyroid with radioactive iodine 131 or propylthiouracil demonstrated normal perilymph sodium and potassium levels but increased auditory thresholds for N1N2 response and brain stem evoked audiometry as well as a crystallized consistency of the bone of the bullae and cochleae, ossicular abnormalities, obliteration of the oval and round window, large dark staining lipid accumulations in Hensen's cells, large intercellular spaces in the stria vascularis with degeneration of the marginal and intermediate cells, inner and outer hair cell degeneration, debris in the cochlear duct, and tectorial membrane irregularity. Otic capsule biochemical alterations were identified which may account for the osseous changes observed morphologically. The morphological, biochemical, and electrophysiological findings in this study support the hypothesis that the cochlea is a site of lesion for sensorineural hearing loss in hypothyroidism. Middle ear changes identified could be responsible for the conductive component.

Stimulation of human monocyte and polymorphonuclear cell iodination and interleukin-1 production by epigallocatechin gallate. (-)Epigallocatechin gallate (EGCg) stimulated iodination of human peripheral blood monocytes, polymorphonuclear cells (PMN), and human promyelocytic leukemic HL-60 cells, dependent on time, dose, and temperature. However, EGCg did not affect iodination of nonadherent peripheral blood mononuclear cells, red blood cells, or 11 other cultured cell lines. Although various immunoregulators such as lipopolysaccharide (LPS), opsonized zymosan, 12-O-tetradecanoylphorbol-13-acetate (TPA) and tumor necrosis factor stimulated PMN iodination to varying degrees, their ability to stimulate monocyte iodination was much lower than that of EGCg. Washout experiments demonstrated that contact with EGCg for less than 60 min irreversibly stimulated PMN and monocyte iodination. EGCg also potently stimulated the production of interleukin-1-like factor by monocytes. The data suggest that EGCg is a strong in vitro stimulant of human phagocytes.

Prolonged propionyl-L-carnitine pre-treatment of rabbit: biochemical, hemodynamic and electrophysiological effects on myocardium. Recently it has been reported that prolonged treatment with propionyl-L-carnitine, a carnitine derivative, results in a positive inotropic effect. To gain further insight into its mode of action, we pre-treated 253 rabbits for up to 10 days with daily doses of 1 mmol/kg propionyl-L-carnitine or L-carnitine intraperitoneally, using saline-treated animals as control. Twenty-four hours after the last injection, we isolated papillary muscles for electrophysiological investigations. Whole hearts were used in perfusion experiments for biochemical and hemodynamic measurements. In addition, mitochondria were harvested from these hearts for the analysis of their function. Plasma and cardiac levels of free carnitine, along with plasma short-chain acylcarnitines, increased at least two-fold after treatment with carnitine or its propionyl-ester, with concomitant rises in tissue long-chain acylcarnitine and long-chain acyl-CoA. At the time of animal sacrifice, treatment did not increase plasma or tissue propionyl-L-carnitine content. The studies carried out with perfused hearts and isolated mitochondria failed to show an effect of propionyl-L-carnitine pre-treatment on high-energy phosphate metabolism or respiration. Papillary muscles from animals, treated for 10 days, showed a lengthening of the action potential duration from 63 +/- 4 to 102 +/- 6 ms (P less than 0.001) at -10 mV. Perfused hearts from these rabbits displayed positive inotropy, as indicated by an improved pressure development at higher ventricular filling volumes, e.g., from 39 +/- 4 to 60 +/- 3 mmHg (P less than 0.05) at 3.6 ml. Pre-treatment with L-carnitine or saline failed to affect the electrophysiological and hemodynamic variables. Thus, prolonged treatment of rabbits with propionyl-L-carnitine, but not with L-carnitine, improved contractility and lengthened action potential duration in isolated muscle preparations.

Functional preservation of the mammalian kidney. IV. Functional effects of perfusion with dimethyl sulfoxide (DMSO) at normothermia. Rabbit kidney were perfused at 37degreesC with various concentrations of DMSO in a K+-Mg2+-rich perfusate. The effects of DMSO on various functional parameters of the rabbit kidney perfused for 60 min were compared with the functional effects of perfusion without DMSO under the same conditions. DMSO produced deviations in vascular resistance and perfusate flow rate from control values. In kidneys perfused with 1.4 and 2.8 M DMSO these vascular changes resulted in changes in GFR at relatively unchanged filtration fractions. The closely parallel relationship between changes in GFR and urine flow in all groups indicates that perfusion per se or perfusion with DMSO may shift the regulation of urine flow rate from tubular reabsorption, which obtains in the in vivo situation, to glomerular filtration. This view was supported by the relatively unchanged parameters of Na+ reabsorption and fractional water excretion during perfusion with all concentrations of DMSO. Additionally, DMSO perfusion resulted in significantly greater weight gains than those observed in kidneys perfused without DMSO, and significantly depressed clearances of PAH, with 2.1 and 2.8 M DMSO.

Genes encoding a histone H3.3-like variant in Arabidopsis contain intervening sequences. Two genes encoding a particular H3 histone variant were isolated from Arabidopsis thaliana. These genes differ from the H3 genes previously cloned from Arabidopsis and other plants by several interesting properties: (1) the two genes are located close to each other; (2) their coding regions are interrupted by two or three small introns, the two closest to the initiation codon being located at the same place in the two genes; (3) another, long intron is located in the 5'-untranslated region just before the initiation codon of gene I as deduced from the sequence of several corresponding cDNAs, and very likely also of gene II; (4) these genes do not show preferential expression in organs containing meristematic tissues contrary to the classical intronless replication-dependent histone genes, thus suggesting that their expression is not replication-dependent; (5) the protein encoded by both genes is the same and corresponds to a minor H3 variant highly conserved among all the plant species studied up to now. All these characteristics are common with the animal replication-independent H3.3 histone genes and it is assumed that the genes described here are the first example of the equivalent H3.3 gene family in plants. Interestingly, the promoter regions of the two genes have the same general structure as the Arabidopsis intronless genes. Possible implications on the regulation of H3 genes expression are discussed.

Leisure activities of retired persons in the United States: comparisons with retired persons in the People's Republic of China. This study was undertaken in view of the large and growing numbers of retired persons in the People's Republic of China; the dearth of information about how they spend their time; and the importance of such knowledge in guiding city reform and accomplishing the Four Modernizations and the future cause. The discretionary-activity patterns and rates, the importance of these activities, and their perceived impact upon the health of 551 retired persons and 100 employed workers in Shanghai were compared in order to investigate the role of retirement in China. To assess similarities and differences between retired persons in China and in the West, the activity patterns and rates of retired Chinese adults were compared with retired adults in two samples from the United States (352 from San Antonio and 899 from San Francisco).

Transition of nystagmus types in unilateral labyrinthine diseases. In order to clarify changes in spontaneous and positional nystagmus which occurred during the course of peripheral labyrinthine diseases, 31 patients with Ménières disease (17 cases), aural vertigo of unknown etiology (9 cases), and sudden deafness (5 cases) were tested repeatedly using ENG. The testing of each case was made 4.8 times on the average with an average interval of 7.2 days. Twenty-four cases (77.4%) showed more than two of the following four types which are listed in serial order of occurrence: spontaneous (or direction-fixed positional) nystagmus toward the involved ear; geotropic direction-changing positional nystagmus; spontaneous (or direction-fixed positional) nystagmus toward the opposite ear; and apogeotropic direction-changing positional nystagmus. Thus, the above-mentioned order may be regarded as the uniform pattern in the nystagmus transition caused by acute unilateral labyrinthine diseases.

Surgical implications of acid ingestion. Ingestion of mineral acid may be accidental or intentional. This form of corrosive usually sears the esophageal mucosa only to produce major injury to the stomach. The prepyloric antrum is almost always injured, but the fundus and cardia may be involved if the stomach is empty at the time of ingestion. Clinically, significant esophageal injury occurs in less than 20 per cent. Initial treatment is supportive, with early operation reserved for patients with severe ingestion in whom gastric necrosis rapidly ensues. In the more typical patient, however, late gastric outlet obstruction still makes surgical therapy mandatory. Subtotal gastrectomy with Billroth I reconstruction is usually possible and is the treatment of choice. Total parenteral nutrition is a useful adjunct.

Induction of glutathione S-transferase isoenzymes in mouse liver by 5-(2-pyrazynl)-4-methyl-1,2-dithiole-3-thione (oltipraz). Treatment of mice with a single dose of oltipraz (OPZ) at 200 mg/kg led to a significant (P less than 0.05) increase in hepatic cytosolic glutathione S-transferase (GST) activity and content. GST activity monitored with 1,2-dichloro-4-nitrobenzene was increased 3.8-fold 3 days after treatment, suggesting the induction of mu class isoenzymes. Ethacrynic acid, a marker for pi class isoforms, showed only a slight increase in GST activity while no induction was observed with cumene hydroperoxide, an indicator for the alpha class. The increase in mu class isoenzymes was further confirmed by separation of the mouse liver affinity purified GST by chromatofocusing and also by resolving the GST subunits by reverse-phase high performance liquid chromatographic procedures. Therefore, OPZ induces mainly the mu class isoenzymes in mouse hepatic tissues.

Myofibrillar proteins, enzyme activity and fibre types in human skeletal muscle. The myofibrillar proteins and relative LC-3 content of myofibrils prepared from five different, left and right muscles of the human forearm were studied by electrophoresis in 10% SDS-polyacrylamide gels followed by densitometry. The specific K-activated ATPase activity of the myofibrillar myosin of the myofibrils was determined and the distribution of the fibre types was analyzed by histochemical methods. The qualitative pattern of the myofibrillar proteins was found to be identical in the different muscles; in the other parameters, however, a variation in a narrow range was observed. The relative LC-3 content, the ATPase activity and the type II fibre content of the right side muscles were always higher than those of the corresponding left side muscles.

Structural deformation of the preterm trachea during acute distention and collapse. The compliant airways of the premature neonate undergo episodic distention and collapse in response to changes in transmural pressure such as occur during spontaneous breathing, mechanical ventilation, and various therapeutic maneuvers. To identify and quantitate the effects of distending and collapsing transmural pressures on the structure of immature airways, tracheal segments from fetal rabbits, fixed at 0, +30, and -30 cm H2O transmural pressure, were examined using histologic and morphometric techniques. In comparison to control sections fixed at 0 cm H2O transmural pressure, application of distending pressures led to evagination of the posterior tracheal wall and significantly increased (P less than 0.05) cross-sectional area, antero-posterior diameter, circumference and muscle length, and decreased muscle thickness. Collapsed tracheal segments (-30 cm H2O) demonstrated invagination of the posterior wall and significantly (P less than 0.05) lower cross-sectional area, and antero-posterior diameter compared to the control segments; all the other parameters remained relatively unchanged. These data demonstrate extreme changes in tracheal geometry in response to the acute application of transmural pressure. From a methodological perspective, these observations suggest that fixation pressures may present significant artifact in histological analyses. Functionally, the noted deformation may lead to alterations in anatomic dead space and airway resistance, and mechanical function of the airways; all of which may compromise respiratory status in ventilated premature infant.

A novel anti-inflammatory peptide from human lipocortin 5. 1. A novel anti-inflammatory peptide (residues 204-212) of human recombinant lipocortin 5 (hrLC5) found on the high similarity region with uteroglobin is described. 2. Peptide 204-212 dose-dependently inhibited the contractions of rat isolated stomach strips elicited by porcine pancreatic phospholipase A2 (PLA2). Contractions caused by arachidonic acid (AA), prostaglandin E2 (PGE2) and 5-hydroxytryptamine were not affected. No direct enzyme inhibition was observed in a radiochemical assay. 3. PGE2 release by both human fibroblasts and rat macrophages was reduced by peptide 204-212 in a dose-dependent manner. 4. The development of carrageenin-induced oedema in rats was significantly inhibited by the local administration of peptide 204-212. 5. The pattern and potency of the biological effects of peptide 204-212 are similar to those of antiflammin 2, a lipocortin 1-derived peptide. 6. It is suggested that peptide 204-212 may represent the active site responsible for the anti-inflammatory properties of lipocortin 5.

Late failure in vein grafts: mediating factors in subendothelial fibromuscular hyperplasia. Late failure of autologous vein grafts often results from excessive subendothelial fibromuscular hyperplasia. Varying factors have been implicated in this process, but the exact etiology remains unclear. In this study, three groups of animals were studied which had sections of common carotid artery replaced with autologous vein grafts. Group I had simple replacement, while Groups II and III had grafts supported by either tightly woven or loose mesh dacron prostheses. Thrombosis occurred only in the unsupported grafts. Unsupported grafts also had more subendothelial proliferation when compared to the loose mesh group. The combined thickness of the intima-media correlated inversely with the number of vasa present within the vein graft wall, i.e. significantly more vascularization was found in the mesh supported group when compared to the other groups. Grafts supported with the tightly woven prosthesis were relatively impervious to the ingrowth of vasa vasora. The data suggest that persistent distension of the graft wall by intra-arterial pressure influences the degree of subendothelial fibromuscular hyperplasia and may be interrelated to revascularization of the graft wall per se.

Doxorubicin interactions at the membrane: evidence for a biphasic modulation of inositol lipid metabolism. Doxorubicin, when incubated for 30 minutes with [32P]-labelled human erythrocyte membrane vesicles, produced an elevation of [32P]inositol-1,4,5-trisphosphate levels. The maximum rise was obtained with 10(-8) mol/l doxorubicin [132 (S.E. 13%) of control, n = 6, P = 0.001]. However, when the inositol lipids were examined, there was no evidence that doxorubicin stimulated the breakdown of [32P]phosphatidylinositol-4,5-bisphosphate under resting conditions, suggesting that the elevated levels of [32P]inositol 1,4,5-trisphosphate were not the result of the stimulation of phospholipase C. Instead, it was found that the dephosphorylation of inositol 1,4,5-trisphosphate by a 5'-phosphomonoesterase was partially inhibited by 10(-8) mol/l doxorubicin so that the rise in [32P]inositol 1,4,5-trisphosphate resulted from the inhibition of the breakdown of constitutively released [32P] inositol 1,4,5-trisphosphate. Similar data was also obtained with another aminoglycoside antibiotic, neomycin. The release of [32P] inositol 1,4-bisphosphate and [32P] inositol 1,4,5-trisphosphate and the breakdown of the inositol lipids in response to calcium (2.5 x 10(-4) and 10(-3) mol/l) stimulation was enhanced by doxorubicin (10(-6) to 10(-12) mol/l). These effects on resting and stimulated inositol lipid metabolism are discussed with reference to the paradoxical effects of doxorubicin to both stimulate and inhibit proliferation, according to concentration.

Occurrence of reiterated sequences in an untranslated region of Simian virus 40 DNA determined by nucleotide sequence analysis. An earlier report (Subramanian, Dhar, and Weissman, 1977c) presented the nucleotide sequence of Eco RII-G fragment of SV40 DNA, which contains the origin of DNA replication. The nucleotide sequence of Eco RII-N fragment located next to Eco RII-G on the physical map of SV40 DNA is presented in this report. Eco RII-N is found to be a tandem duplication of the last 55 nucleotides of Eco RII-G. This tandem repeat is immediately preceded by two other reiterated sequences occurring within Eco RII-G, one of them being a tandem repeat of 21 nucleotides and the other a nontandem repeat of 10 nucleotides. These repetitive sequences occur in close proximity to the origin of DNA replication which is known to contain other specialized sequences such as a few palindromes (one of which is 27 long and possesses a perfect 2-fold axis of symmetry), one "true" palindrome, and a long A/T-rich cluster. The repeats (and the replication origin) occur within an untranslated region of SV40 DNA flanked by (the few) structural genes coding for the "late" proteins on the one side and that (those) coding for the "early" protein(s) on the other side. The reiterated sequences are comparable in some respects to repetitive sequences occurring in eucaryotic DNAs. Possible biological functions of the repeats are discussed.

In vitro study of clavulanic acid in combination with penicillin, amoxycillin, and carbenicillin. The activity of clavulanic acid alone and in combination with penicillin, amoxycillin, and carbenicillin was studied. Marked reductions in the minimum inhibitory concentrations (MICs) for a wide spectrum of beta-lactamase-producing clinical isolates were found. Of particular interest were the decreased MICs of penicillin for Bacteroides fragilis and beta-lactamase-producing strains of Neisseria gonorrhoea in the presence of the clavulanic acid. Beta-lactamase-producing strains of Escherichia coli, Klebsiella spp., and indole-negative Proteus also showed considerably increased susceptibility to amoxycillin in combination with clavulanic acid. Two beta-lactamase-producing strains of Pseudomonas aeruginosa remained resistant to carbenicillin in the presence of clavulanic acid.

Structural and immunoreactive characteristics of hepatitis B core antigen. The ultrastructural study of liver tissues from 38 patients with type B viral hepatitis consistently showed the presence of hepatitis B core antigen of 21-25 nm size in the liver cell nuclei and to a lesser extent in the cytoplasm. This finding and the demonstration of the tubular form of hepatitis B surface antigen in the proliferative degranulated endoplasmic reticulum constituted the etiologic criterion for the diagnosis of the disease. The double-shelled Dane-like particles were frequently found in association with the tubular form of the surface antigen. The core particles were found in the protoplasmic processes of hepatocytes and this correlated with the immunofluorescent microscopic findings that the antigen may be shed into circulation with the protoplasm. The core antigen was found to resist digestion by various enzymes such as protease, DNase, RNase, phospholipase C, lipase, lysozyme, diastase, neuraminidase and hyaluronidase, all of which did not destroy the immunoreactivity as demonstrated by immunoelectron and immunofluorescent microscopy. Similarly, sodium dodecyl sulfate, Tween 80 and mercaptoethanol also had no effect. The formalin-fixed paraffin-embedded liver tissue sections could be treated with protease to facilitate the immunofluorescent staining for the core antigen in tissue.

[Brain infarcts in humans during middle age and senility. I. Defects of blood-brain barrier permeability in immunocytochemical studies]. Brains of the deceased in the age from 45 to 57 years (6 cases) and from 80 to 101 years (9 cases) with ischemic brain damage were studied. Technique of the peroxidase-antiperoxidase (Sterberger et al. 1970) was used for visualization of the brain tissue reactivity for albumin, IgG, alpha 1-antitrypsin and alpha 2-macroglobulin. In all cases the disturbances of the blood vessels permeability were found. The BBB deterioration within the first days of brain infarct seems to be smaller in senile age than in middle age. However, after some days senile blood vessels permeability increases and become similar in both age groups.

A new balloon-expandable tantalum coil stent: angiographic patency and histologic findings in an atherogenic swine model. The angiographic patency and histologic characteristics of a new balloon-expandable tantalum stent were studied after implantation intervals ranging from 1 to 32 weeks in atherogenic miniature swine peripheral and coronary arteries. Stents were placed in 34 arteries (10 coronary and 24 iliac arteries) in a total of 13 swine. Two swine died within 24 h of stent implantation. Follow-up angiography was performed before death was induced in 11 swine (8 coronary and 19 iliac arteries) and revealed 100% patency without evidence of lumen stenosis, thrombosis or migration of the stents. The neointimal thickening was maximal at 4 weeks after stent implantation and was at its minimum at 32 weeks after implantation with reendothelialization of the stents generally complete at that time. An advantage of this balloon-expandable device is its inherent longitudinal flexibility. The coil configuration allowed the nondeployed stent to negotiate acute bends in coronary arteries to reach the site of implantation and also allowed the deployed stent to conform to the natural contour of tortuous coronary arteries. The tantalum device was remarkable for its radiographic visibility, which greatly aided its placement under fluoroscopic guidance. This study demonstrates this stent's ease of implantation, excellent patency rate and absence of restenosis due to neointimal proliferation for up to 8 months in this atherogenic swine model.

Cushing's disease with cyclic hormonogenesis and diabetes insipidus. A cyclic excess of cortisol secretion was detected in a patient with diabetes insipidus and diabetes mellitus. The cycles of hypercortisolism were of 7 days' duration, but during the nadir of these cycles urinary excretion of corticosteroids and 17-ketosteroids was within the normal range. The radiological appearance of the sella turcica was normal; however, computerized axial tomography of the head revealed a small tumor immediately superior to the sella turcica. At operation a small chromophobe adenoma superior to the diaphragma sellae and involving the hypophysial stalk was partially resected. Postoperatively, the patient continued to have 7-day cycles of increased corticosteroid excretion, but the amounts excreted were less than they had been preoperatively. Other patients have been described in whom Cushing's disease has been due to cyclic hypercortisolism. These cycles have been remarkably regular in individual patients, but of variable duration in different patients. Furthermore, cyclic hormonogenesis probably occurs in a variety of endocrinopathies. (Neurosurgery, 5: 598--603, 1979).

Clinical efficacy of carvedilol in severe hypertension. In an open clinical study, the efficacy and safety of carvedilol was investigated in 26 severely hypertensive patients controlled inadequately on a diuretic [diastolic blood pressure (DBP) greater than 120 mm Hg at first visit and greater than 110 mm Hg following more than 1 week administration of a diuretic]. Following diuretic treatment all patients were initially administered 5 mg of carvedilol once daily. The dose was gradually increased to 10 mg and 20 mg until DBP was reduced below 100 mm Hg or until it was reduced by at least 10 mm Hg. Antihypertensive activity of carvedilol (5 mg) was sufficient in only three cases, but after 4 weeks (inpatients) or 8 weeks (outpatients) administration of carvedilol (10 mg or 20 mg), DBP/systolic blood pressure was significantly reduced from 176 +/- 6/117 +/- 3 to 145 +/- 3/94 +/- 2 mm Hg (p less than 0.001) in all patients. Overall, a sufficient antihypertensive effect was observed in 80% of the patients. Heart rate was significantly decreased from 76 +/- 2 to 67 +/- 2 beats/min, but no patient experienced bradycardia. Carvedilol was generally well tolerated. These findings suggest that 10-20 mg of carvedilol once daily, in combination with a diuretic, is an effective and safe treatment for patients with severe hypertension.

[A simple method for the synthesis of phosphatidylcholine with the fatty acid substituted in the 2-position]. The preparation of PC with the 14C-fatty acids palmitic, stearic, oleic and linoleic acid at OH-group in position 2 is described. The starting material is egg yolk lecithin. By the attack of snake venom phospholiphase lyso-PC is produced which is reacylated by the appropriate fatty acid anhydride. In comparison with the methods published up to now this preparation has the advantage of higher yields and greater simplicity. By means of in vivo synthesis it is impossible to get PC species with only one fatty acid in a defined position. Working with radioactive fatty acids the specific radioactivity can be adapted to the requirements. The procedure can be made on a semi-technical scale.

[Cushing's syndrome: the diagnostic and treatment problems in 27 cases]. Problems of diagnosis and treatment were analyzed in 27 patients with Cushing syndrome (25 confirmed by anatomic findings) followed for a mean of 50 months. The etiology was Cushing disease in 14 (52%), suprarenal tumor in 9 (33%) and ectopic secretion of ACTH in 4 (15%). Determination of plasma cortisol levels at 4 PM or 11 PM was a highly sensitive test for the presence of this syndrome (100%). High resolution computed tomography was considerably more effective than conventional X ray studies of the sella in patients with Cushing disease (42 vs 20%). Treatment has been totally effective in all patients with benign suprarenal lesions. Cure was obtained in 64% of patients with pituitary lesions and 0% of patients with Cushing syndrome associated to malignancy.

Gonadotrophin-releasing hormone analogues as therapeutic probes in human growth and development: evidence from children with central precocious puberty. Statural growth and skeletal development were assessed in 87 girls with idiopathic central precocious puberty (CPP) during gonadotrophin-releasing hormone analogue (GnRHa)-induced suppression of gonadarche. Before the start of therapy, mean chronological age (CA) was 6.3 years and mean bone age (BA) was 10.6 years. During up to 6 consecutive years of complete suppression of gonadal sex steroid secretion, the mean height velocity decreased from 10.8 cm/year to prepubertal rates. At each interval height velocity was found to be inversely and negatively correlated with BA such that girls with advanced BAs grew at rates well below prepubertal norms but appropriately for their degree of skeletal maturation. Skeletal maturation similarly slowed during prolonged GnRHa administration (delta BA/delta CA = 0.6 +/- 0.1 over 3 years, mean +/- SD, n = 66) and was also negatively correlated with the BA before the start of therapy. Predicted adult height increased progressively during therapy; however, when analysed as changes in height SDS(BA), the impact of treatment was variable and correlated positively with the initial degree of skeletal maturation. The effect of GnRHa therapy on growth in children with CPP requires long-term study and is best analysed by employing a developmental perspective.