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Escherichia coli generation in the logarithmic growth phase was inhibited in peptone broth USP at pH 7.0 without kill below 3.0 mug/ml of aminosidine. Above this value, the logarithms of the number of viables of the drug-treated culture ultimately decreased linearly with time and the slopes of these plots were independent of concentration. A concentration-dependent lag in the time of attainment of the cidal action was observed, and the extent of this lag was related to the ease of emergence of resistant organisms. The minimal concentration for cidal action increased with increasing concentrations of nutrients and with decreasing pH. Pretreatment of the cultures with novobiocin and tetracycline lessened the minimum bactericidal concentration of aminosidine whereas chloramphenicol pretreatment increased it. Tetracycline pretreatment inhibited the emergence of aminosidine-resistant organisms.

The elementary osmotic pump is a new delivery system for drugs or other active agents; it delivers the agent by an osmotic process at a controlled rate. Control resides in the: (a) water permeation characteristics of a semipermeable membrane surrounding the formulated agent, and (b) osmotic properties of the formulation. In its simplest embodiment, the system is constructed by coating an osmotically activie solid agent with the rate-controlling, semipermeable membrane. This membrane contains an orifice of critical size through which solubilized agent is dispensed. The system can contain the agent in solid form at loading higher than 90% of the total volume, and the agent can be delivered at rates several orders of magnitude higher than can be achieved by solution diffusion through polymeric membranes. The delivery rate, the fraction of total content delivered at zero order, and the system's delivery portal size have been calculated for delivery of a single compound. Experimental work verified the theory. The release rate from the system was found to be independent of outside agitation when the system is not deformed by shaking action, the pH of the environment, and delivery portal size for sizes within a specified range. The delivery rate from this system in vitro and in the GI tract of dogs was found to be equal.

A method is described for the GLC determination of atenolol BP in plasma and urine. Extraction is accomplished under dehydrating conditions, and interfering impurities are removed by using an acidified cyclohexane-isopropanol mixture (2:1) and charcoal-treated paper disks. The drug thus isolated appears to react more efficiently with heptafluorobutyric anhydride, increasing the sensitivity of GLC electron-capture analysis. Concentrations as low as 0.02 mug/ml were measured using 0.5-ml aliquots of plasma or 0.1 ml of urine. Amino alcohols such as atenolol may form hydrates or alcoholates, precluding complete derivatization with heptafluorobutyric anhydride.

Daily administration of a proprietary magnesium and aluminum hydroxides suspension, 15 ml four times a day, to normal adult volunteers resulted in a statistically significant increase in urine pH on the 1st day of treatment. The urine pH's on the 2nd and subsequent days of treatment were statistically significantly higher than on the 1st day. A 7.5-ml dose of the antacid suspension, taken four times a day, had only a small and not statistically significant effect on urine pH, while 30 ml four times a day increased urine pH by approximately the same magnitude as the 15-ml doses. The effect of the antacid on urine pH persisted for at least 1 day after discontinuation of dosing.

Tribromsalan can be quantitatively measured in whole blood and urine by a technique involving extraction with ethyl acetate, treatment with silica gel, separation by TLC, and quantitative measurement by fluorescent spectrophotometry. This method has a sensitivity down to 125 ng (25 ppb in 5.0 ml of sample) of free tribromsalan and shows an average 90% recovery of tribromsalan in blood and urine with standard deviations of 9.7 and 7.4%, respectively.

The relationship between serum and stimulated, mixed saliva concentrations of procainamide was determined in 12 chronically medicated patients. Samples were obtained at times chosen to approximate the maximum and minimum serum concentrations of the drug during a dosing interval. Marked intersubject variability was found in the ratio of saliva to serum concentration of the drug (0.27-8.93). There was no correlation between the dose (milligrams per kilogram per day) and the minimum serum or saliva concentration of procainamide. Saliva pH ranged from 6.3 to 8.0 in eight subjects. The ratio of saliva to serum concentration of procainamide increased with decreasing pH. This result can be largely explained by the pH-dependent ionization and distribution of procainamide, a weak base.

The cardiovascular effects of intravenously administered strychnine were studied in anesthetized and paralyzed dogs. Administration of strychnine in cumulative doses of up to 0.1 to 0.2 mg/kg caused significant pressor, as well as positive inotropic and chronotropic, effects on the heart which were abolished by adrenergic blocking agents. The cardiovascular responses possibly were elicited by a central mechanism in contrast to the peripheral inhibitory action of strychnine on the sympathetic system. Diazepam caused a marked attenuation of the pressor response with only slight changes on the heart. A combination of diazepam and propranolol would appear to be a useful therapy in cases of strychnine poisoning showing marked cardiovascular excitation.

The administration of guanethidine to adult rats has been shown by morphological criteria to destroy sympathetic neurons. The objective of this study was to evaluate by biochemical and functional criteria the degree and permanence of this sympathectomy. Young adult male rats (260-300 g) were injected with saline (controls) or with guanethidine for 5 weeks. The status of the sympathetic nervous system in the animals was evaluated 1, 3 and 6 to 7 months after cessation of treatment. Seven months after cessation of treatment; the activity of tyrosine hydroxylase in the superior cervical ganglia of treated animals was greatly reduced, as were the norepinephrine levels in peripheral tissues. The concentration of epinephrine and the activity of tyrosine hydroxylase in adrenals were not different from controls at any of the times studied. Norepinephrine concentrations in several areas of the central nervous system were unchanged. Increases in blood pressure in response to stimulation of the sympathetic vasomotor outflow in the pithed rat preparation were markedly and permanently reduced in guanethidine-treated animals. Isolated intestinal nerve-muscle preparations from guanethidine-treated animals usually contracted in response to nerve stimulation, rather than relaxing as in controls. The response to stimulation of the hypogastric nerve in vas deferens preparations was reduced 1 month after cessation of treatment. The responses of the vas deferens from guanethidine-treated and control animals were the same 7 months after treatment despite a 93% reduction in norepinephrine concentration. The data demonstrate that the administration of guanethidine to adult rats produces a marked and permanent destruction of the peripheral sympathetic nervous system.

The mechanism of action of quinidine on squid axons has been examined by means of voltage clamp and internal perfusion techniques. When applied either externally or internally, quinidine HCl suppresses both sodium and potassium conductance increases, the effect on the former accounting for the observed decrease in action potential. The potassium conductance in quinidine undergoes a marked inactivation in a manner dependent upon the membrane potential and time, accounting for the observed prolongation of the terminal falling phase of the action potential. Quinidine methiodide exhibits the effect similar to that of quinidine HCl only when applied internally. The dissociation constants of quinidine in suppressing the sodium conducting system are estimated to be 2.4 x 10(-4) and 4.0 x 10(-4) M for quinidine HCl and methiodide, respectively. The dissociation constant of quinidine in suppressing the potassium-conducting system decreases with increasing step depolarization. When applied externally to the intact axons, quinidine HCl is more effective at external pH 8.6 than at 7.3. When perfused internally, quinidine HCl is more effective at internal pH 7.0 than at 8.0, and the potency is related to the calculated internal concentration of the charged form rather than that of the uncharged form. These results lead to the conclusion that quinidine HCl penetrates the nerve membrane in the uncharged form, is ionized in the axon and blocks the sodium and potassium conductances primarily in the charged form. Thus, quinidine and local anesthetics share some features in the terms of the site of action and active form.

The effects of two barbiturates on calcium uptake by sympathetic ganglia have been examined. Sodium pentobarbital (0.4-0.75 mM) and sodium thiopental (0.3 mM) block the preganglionic stimulation-induced uptake of 45Ca by rat superior cervical ganglia but not action potential conduction in the presynaptic axons. The ganglionic-blocking agent, tetraethylammonium, does not inhibit stimulation-induced Ca uptake and does not prevent the blocking effect of thiopental. This effect is therefore probably presynaptic. Postassium-rich media also stimulate Ca uptake by the ganglia, and this effect is markedly inhibited by pentobarbital. Since the K stimulation effect is also observed in deafferented ganglia but not in guanethidine-denervated ganglia, this effect is probably associated primarily with postsynaptic elements. In sum, the data suggest that the barbiturates inhibit Ca permeability changes in both pre- and postsynaptic neurons.

1. Electrical and mechanical activities of the longtitudinal muscle of the dog antrum were recorded with the double sucrose-gap technique. 2. The muscle exhibited spontaneous action potentials which consisted of a spike-like potential which, after a brief and partial repolarization, was followed by a negative-going, plateau-type potential. In 97% of the preparations, no tension changes were produced by spontaneous action potentials. 3. Tetrodotoxin, atropine, alpha- and beta-adrenoceptor antagonists, and H1 and H2 receptor blocking agents had no effect on the action potential. It was concluded that the action potential was myogenic in origin. 4. The mean frequency of the action potential at 37+/- 0.5 degrees C was 1.0/min+/-0.06 (s.e. of mean, n=92) and the mean duration 7.1+/-0.2 sec (s.e. of mean, n=11). 5. Steady depolarizing current increased whereas hyperpolarizing current decreased the frequency of the action potential. 6. Length-tension relations were studied. In twelve strips, the average resting, passive, tension at LO was 570 mg. The active force of isometric contraction produced by acetylcholine increased with strip length up to a maximum, then decreased wtih further increased in length. There were no mechanical responses to pentagastrin. 7. Pentagastrin had two sites of action. On smooth muscle, it increased the frequency of the action potential in a dose dependent fashion. Threshold concentraions ranged from 2X10-14 to 10-11M. The ED50 was 2X10-10M. The maximum response, 5.4/min, was reached at 10-8M. Pentagastrin also released acetylcholine from intramural cholinergic nerves. 8. Pentagastrin reduced the amplitude and duration of the action potential.

1. Diethyl ether, which is known to be partly metabolized in vivo, has been found to show an O2 uptake with the rat liver microsomal membranes; a similar reaction is given with other short chain aliphatic ethers, isoproply and n-butyl ether. 2. The "etherase" reaction is optimal at pH 7.2-7.4 and is not accompanied by an increased formation of malondialdehyde. 3. When CoA is added to the microsomes together with a source of oxaloacetate and the consensing enzyme synthase, the etherase present forms citrate from diethyl ether, indicating an acetylation of CoA, which then enters the citric acid cycle. 4. Similarly to 3, fluorocitrate is formed from methyl fluoroethyl ether. 5. Differing from plasmalogens, a tetrahydropteridine does not have to be added as a co-factor.

The internal pH of crab muscle fibres was measured using recessed-tip pH-sensitive micro-electrodes. Immediately following electrode penetration the mean internal pH was 7-21 +/- 0-02 (S.E. of mean) and the mean membrane potential was -64-9 +/- 0-6 mV (S.E. of mean). If H+ ions were passively distributed across the fibre membrane the internal pH would have been 6-39. 2. The internal pH tended to rise before stabilizing at a mean value of 7-27 +/- 0-02 (S.E. of mean). The difference between immediate and stabilized values is highly significant and suggests acid injury on electrode penetration. 3. Changing the membrane potential or external pH had only small, slow effects on internal pH. 4. External CO2 caused a large and rapid decrease in internal pH. With low concentrations of CO2, the effect was dependent on the initial pH as predicted by the Law of Mass Action. During a long exposure to 2-65% CO2 at pH 7-5, the internal pH returned slowly to its previous value, suggesting active transport of H+ (or OH- or HCO3-) ions across the fibre membrane. 5. The internal buffering power calculated from the response to 2-65% CO2 was 47-3 +/- 2-8 slykes (m-equiv H+/pH unit per l.) (S.E. of mean).

1. The amounts of oxytocin released during Ferguson and vago-pituitary reflexes are estimated by measurements of intramammary pressure. For the milk-ejection reflex, the gain in weight of the young over a period of 30 minutes is taken as an indirect index of the release of oxytocin. 2. Antagonists of specific cholinoceptors and adrenoceptors were injected into the third ventricle in order to delineate the role of the mediators and receptors in the control of oxytocin release. 3. The results suggest that three reflexes have a specific chemical transmission since: a) The Ferguson reflex is inhibited by the drugs that only block alpha and beta adrenoceptors. b) The vago-pituitary reflex is inhibited by the drugs that block alpha and beta adrenoceptors and muscarinic cholinoceptors. c) The milk-ejection reflex is inhibited by the drugs that block alpha adrenoceptors and muscarinic and nicotinic cholinoceptors.

Oviducal fluid was collected by cannulation from four cows and by irrigation from fifteen slaughtered cows. The proteins in the fluid were examined by polyacrylamide gel electrophoresis at pH 4-5 and pH 8-9, isoelectric focusing on polyacrylamide, immunodiffusion, immunoelectrophoresis, affinity chromatography and gel filtration. The macromolecular components found were mainly serum proteins but small amounts of other proteins were detected in oestrous and dioestrous samples by electrophoresis at pH 8-9 following fractionation of the fluid by gel filtration or affinity chromatography. Small amounts of cathodically migrating proteins were detected directly by electrophoresis at pH 4-5 in dioestrous samples but not in oestrous samples. Determination of glycosidase activities revealed that the levels at oestrus were similar to the levels detected in serum. At dioestrus, the activities of B-N-acetylgalactosaminidase and beta-N-acetylglucosaminidase were elevated.

About 30% of boar seminal plasma nitrogen is maximally precipitated at room temperature by 6 to 10 mM zinc in citrate solution at pH 8. A rise in the total nitrogen precipitated by 1 to 6 mM zinc is accompanied by a fall in the haemagglutinin titre of the supernatant fluid. At 6 mM zinc addition, 95% of the haemagglutinin is precipitated, but much of this is recoverable by re-solution of the zinc precipitate. Protein profile studies by gel-filtration chromatography of the zinc precipitate solution reveals a mixture of proteins, some of which are not by themselves zinc-precipitable.

Season had a pronounced effect upon seminal pH and refractometer 'protein', total carbohydrate, dry weight, total N2 and lactic acid in seminal plasma of first and second ejaculates. In addition, total seminal volume, spermatozoa per ml and per ejaculate, non-protein sulphhydryl and glycerylphosphorylcholine of second ejaculates were also influenced. There was a season difference in the concentrations of lactic acid in spermatozoa from first and in total N2 from spermatozoa in second ejaculates. The effects of season on seminal plasma were greater than those on spermatozoa. Spermatozoa in first ejaculates were less affected by season than those in secons ejaculates. This differential effect on first and second ejaculates was generally true of all seminal characteristics.

Approximately 1 week was required to stabilize the extragonadal sperm reserves in stallions ejaculated daily for 10 weeks. The true daily sperm output of a stallion was equal to the mean daily sperm output of seven ejaculates +/- 1-35 X 10(9) spermatozoa. Mean concentrations of spermatozoa/ml and number of spermatozoa/ejaculate were higher (P less than 0-01) for X1 and X3/week ejaculation frequencies than for a X6/week frequency. Sperm output/week was nearly identical for a X6/week frequency. Sperm output/week was nearly identical for the X3 and X6 frequencies and higher (P less than 0-01) than the X1 frequency. Increase of ejaculation frequency from one to two ejaculates/day twice weekly significantly (P less than 0-01) raised the output of spermatozoa/week. Gel-free semen volume, spermatozoa/ml, and number of spermatozoa/ejaculate were higher (P less than 0-01) in the first, than in the second, ejaculate. Collection of semen on alternate days would be a practical ejaculation frequency for inseminating mares. Two ejaculates collected twice a week would be a practical ejaculation frequency for long-term storage of stallion semen.

Mares and fetuses with indwelling catheters in the umbilical and uterine vessels have been used to monitor transplacental blood gas tensions, pH, O2 affinities and the concentration of various metabolites in fetal and maternal blood during late gestation. Measurements of umbilical and uterine blood flows and arterio-venous differences enabled the uptake of O2 and glucose by the fetus and the uterus to be estimated. The present findings are compared with those from other species in comparable conditions.

Total androgens, testosterone and total oestrogens were measured in twenty-one intact, nine unilaterally cryptorchid, three bilaterally cryptorchid stallions and four geldings. Total oestrogens were significantly higher (P less than 0-005) and total androgens significantly lower (P less than 0-05) in the bilateral cryptorchid compared to other groups. There was a significant (P less than 0-025) day and night variation in total androgen levels. Thyroidectomized and intact animals showed a marked decrease in total androgen as well as testosterone levels during the winter period thus showing an effect of season on androgenic function of the testis. Disappearance rate of total and androgens following castration was extremely rapid and levels were undectable within 12 hr. Sexual stimulation appeared to increase total androgen levels. Testosterone, androstenedione, dihydrotestosterone, androstandiols, and androstenediol were identified in spermatic vein blood. Dihydrotestosterone was measured in fluid from the cauda epididymidis.

The clinical course of 40 patients with polyarteritis was reviewed to determine prognostic factors and response to treatment. The first three months were the most critical to survival. Survivorship was 57 per cent at five years. Older age of onset, involvement of skeletal muscle and presence of peripheral neuropathy weighted against a satisfactory outcome. Cutaneous vasculitis was associated with a more benign course. Myocardial disease, central nervous system involvement, or hypertension were not invariably poor prognostic factors. Muscle biopsies, even in the absence of clinical involvement, were a useful diagnostic procedure, and renal angiograms were found to be a valuable alternative to renal biopsy. An unequivocal distinction on clinical and histopathologic criteria could not be made among polyarteritis nodosa, hypersentitivity angiitis, and allergic granulomatosis. Australia antigenemia occurred in six per cent of patients. Although evaluation of therapy was difficult, data from this study did not show a superiority of high vs. low dosage of corticosteroids in suppressing active disease.

The synthesis of beta-phenylethanolamine analogs in which the phenyl ring is replaced by cyclohexyl, cyclohexen-4-yl, cyclooctyl, cyclooctenyl, cycloocta-1,3-dien-2-yl, cycloocta-1,5-dienyl, and cyclooctatetraenyl was accompanied by conversion of the corresponding aldehydes to the cyanohydrins followed by reduction with lithium aluminum hydride. A preparatively useful synthesis of 1-formylcyclooctatetraene is described utilizing the photocycloaddition of methyl propiolate to benzene followed by reduction to the alcohol and oxidation with MnO2. All compounds, as their hydrochloride salts, exhibited indirect adrenergic activity on the rat vas deferens. On the reserpinized rat vas deferens all compounds potentiated the effects of exogenous norepinephrine. The results are in agreement with the conclusion that the more saturated the ring moiety, the greater the affinity for the amine uptake site of the vas deferens and suggest that there is no important interaction between the drug and this uptake site that involves pi-complex formation.

The syntheses of trans- and cis-1-benzyl-3-dimethylamino-6-phenylpiperidine (1 and 2) are described. Compounds 1 and 2 were found to be inhibitors to histamine, acetylcholine, and barium chloride induced contractions of the isolated guinea pig ileum. Compounds 1 and 2 do not exhibit appreciable stereoselectivity in their ability to inhibit smooth muscle contractions. The cis compound 2 is a more effective inhibitor of histamine N-methyltransferase than the trans isomer 1.

Crystalline perchlorate salts of aziridinium ions derived from phenoxybenzamine and dibenamine were prepared. Both aziridinium ions were tested on the rat vas deferens and found to possess alpha-adrenergic potencies which were nearly identical with those of the parent compounds. The hydrolysis rates of phenoxybenzamine and dibenamine aziridinium ions (2a,b) in physiological medium were found to be 6.0 4 x 10(-4) and 8.35 x 10(-4) sec-1, respectively. The rates of cyclization of the parent amines to 2a and 2b in aqueous medium were 1.9 x 10(-2) and 7.2 x 10(-3) sec-1, respectively. The potencies and kinetic profiles indicate that the aziridinium ion is the only active species in alpha-adrenergic blockade. Moreover, differences in potency between phenoxybenzamine and dibenamine appear to be exclusively to a difference in receptor affinity rather than to a difference in intrinsic alkylating ability.

When a solution containing gly-N-pa and imidazole is evaporated to dryness and then maintained at a temperature between 65 degrees C and 100 degrees C, high yields of AppA and obligoglycines are obtained. We believe that ImpA is formed first, and then activates the carboxyl group of glycine or gly-A-pA. If glycine, ATP or AppA, and imidazole are heated together in the solid state, ImpA is formed and ATP , or indirectly from imidazole and gly-N-pA. Next the carboxyl group or glycine is activated by the ImpA formed in situ. The subsequent reactions of activated glycine leads to the formation of oligoglycines and the 2' (3')-glycylester of pA. Under plausible prebiobic conditions, good yields of oligoglycines up to the octamer can be obtained from glycine, ATP and imidazole.

The reactions of glycine with inorganic polyphosphates in the solid state have been studied. The formation of peptides up to the decamer occurs at moderate temperatures(r.t.-100 degrees C) in the presence of imidazole and magnesium chloride. If adenosine 5' -monophosphate is added to the reaction mixture, 2'(3') -o-glycyl adenosine 5'-monophosphate is also obtained. These reactions could have occurred on the primitive earth.

A reaction which oligomerizes nucleotides under possible prebiotic conditions has been characterized. Nucleoside monophosphate in the presence of cyanamide at acid pH condenses to form dithymideine pyrophosphate and phosphodiester bonded compounds. Imidazole compounds and activated precursors such as nucleoside triphosphate are not necessary for this ologomerization reaction which produces primarily cyclic ologonucleotides.

When solutions of nucleoside 5'-phosphates and trimetaphosphate are dried out at room temperature, nucleoside 5'-polyphosphates are formed. The Mg++ ion shows a superior catalytic function in this reaction when compared with other divalent metal ions. Starting with nucleoside 5'-phosphates, Mg++ and trimetaphosphate, the predominant products in the nucleoside 5'-polyphosphate series pnN are p4N, P7N and p10N. Nucleoside 5'-diphosphates yield p5N and p8N, nucleoside 5'-triphosphates give p6N and p9N. The prebiological relevance of these reactions is discussed.

One of the major diagenetic pathways of organic matter in recent sediments involves the condensation of cellular constituents, particularly amino acids and sugars, into insoluble melanoidin-type polymers. These polymers consist mainly of humic and fulvic acids and make up the major part of the organic carbon reservoir in recent sediments. We suggest that a similar set of reactions between abiotically formed amino acids and sugars, and more generally between aldehydes and amines, occurred on a large scale in the prebiotic hydrosphere. The rapid formation of this insoluble polymeric material would have removed the bulk of the dissolved organic carbon from the primitive oceans and would thus have prevented the formation of an "organic soup". Melanoidin polymers have several properties which make them attractive hypothetical precursors of contemporary oxidation-reduction coenzymes: 1. they contain heterocyclic nitrogen compounds similar to the nitrogenous bases; 2. they contain a high concentration of stable free radicals; and 3. they tend to concentrate those heavy metals which play prominent roles in contemporary enzymic redox processes. The prebiotic formation of similar polymers could, therefore, have provided the starting point for a basic class of biochemical reactions. We suggest that the prebiotic scenario involved chemical and protoenzymic reactions at the sediment-ocean interface in relatively shallow waters and under conditions not much different from those of the recent environment.

Comparative data on quaternary structure, cooperativity, Bohr effect and regulation by organic phosphates are reviewed for vertebrate hemoglobins. A phylogeny of hemoglobin function in the vertebrates is deduced. It is proposed that from the monomeric hemoglobin of the common ancestor of vertebrates, a deoxy dimer, as seen in the lamprey, could have originated with a single amino acid substitution. The deoxy dimer has a Bohr effect, cooperativity and a reduced oxygen affinity compared to the monomer. One, or two, additional amino acid substitutions could have resulted in the origin of a tetrameric deoxy hemoglobin which dissociated to dimers on oxygenation. Gene duplication, giving incipient alpha and beta genes, probably preceded the origin of a tetrameric oxyhemoglobin. The origin of an organic phosphate binding site on the tetrameric hemoglobin of an early fish required only one, or two, amino acid substitutions. ATP was the first organic phosphate regulator of hemoglobin function. The binding of ATP by hemoglobin may have caused the original elevation in the concentration of ATP in the red blood cells by relieving end product inhibition of ATP synthesis. The switch from regulation of hemoglobin function by ATP to regulation by DPG may have been a consequence of the curtailment of oxidative phosphorylation in the red blood cell. The basic mechanisms by which ATP and DPG concentrations can respond to strss on the oxygen transport system were present before the origin of an organic phosphate binding site on hemoglobin. A switch from ATP regulation to IP5 regulation occurred in the common ancestor of birds.

Imidazole catalysis of phenylalanyl transfer from phenylalanine adenylate anhydride to the hydroxyl groups of homopolyribonucleotides was investigated as a chemical model of the biochemical aminoacylation of tRNA. Imidazole catalyzed transfer of phenylalanine to poly(U) increases from pH 6.5 to 7.7 and decreases above pH 7.7. At pH 7.7 approximately 10% of the phenylalanyl residues are transferred to poly(U). At pH 7.1, transfer to poly(U) was five times as great as to poly(A) and transfer to a poly(A) poly(U) double helix was negligible. At pH 7.1 approximately 45 mole percent linkages to poly(U) were monomeric phenylalanine; the remainder of the linkages were peptides of phenylalanine. The number of linkages and their lability to base and neutral hydroxylamine indicates that phenylalanine and its peptides are attached as esters to the 2' hydroxyl groups throughout poly(U) and the 2' (3') hydroxyl groups at the terminus of poly(U). These results do model the contemporary process of aminoacyl transfer to tRNA and continue to suggest that a histidine residue is in the active site of aminoacyl-tRNA-synthetases.

Lethally irradiated male and female hybrids, parental strains, and the third party strain A mice were inoculated with reciprocal hybrid marrow from donors of the same sex. A graft-versus-host reaction was produced against H-Y antigens of reciprocal hybrids. Although the late mortality in inbred strain males was generally greater than that of females, without further tests this difference was not automatically attributable to an X or a Y chromosome disparity. Hybrids did not recognize the qualitative difference in antigenicity of their reciprocals, but they were able to recognize the quantitatively greater antigenicity of their parental strains, and a hybrid-versus-parental strain reaction occurred. The graft-versus-host reaction in the third party strain A mice was significantly more severe than that produced by hybrid marrow in their reciprocal hybrid recipients, but significantly less severe than that produced in the parental strains. The relationship between antigenicity and responsiveness was such that the severity of the graft-versus-host reactions masked the maternal influences observed with other reciprocal hybrids.

A three-step treatment plan incorporating adoptive immunotherapy and chemoradiotherapy was used to treat AKR (H-2k) mice bearing spontaneous leukemia-lymphoma (SLL). 1) Leukemic mice were treated with chemoradiotherapy for immunosuppression and leukemia cytoreduction. 2) To introduce a graft-versus-leukemia reaction against residual malignant cells, the immunosuppressed AKR mice were given immunocompetent cells from H-2 mismatched DBA/2 (H-2d) donors. 3) To "rescue" the AKR hosts from incipient graft-versus-host disease, the mismatched DBA/2 cells were killed with combination chemotherapy, and cells from allogeneic H-2 matched RF (H-2k) donors were administered to restore hematopoiesis. Leukemic AKR mice thus treated had significant prolongation of their median survival time and a higher 60-day survival rate post treatment than did untreated controls, chemoradiotherapy controls, or control mice that received chemoradiotherapy plus cells from syngeneic donors. Therefore, adoptive immunotherapy may be useful as an adjunct to conventional therapy for treatment of SLL in AKR mice.

The weakly acidic fraction (WAF) of cigarette smoke particulate matter was fractioned by silica get chromatography. We assayed the various primary subfractions for potential tumor-promoting activity by measuring the incorporation of tritiated thymidine into mouse epidermal DNA as induced by these subfractions. Based on these results and on chemical composition, the primary subfractions, were then combined into four major subfractions and tested on initiated mouse skin for tumor-promoting activity by long-term application. Two of these subfractions (40% of WAF) were inactive, whereas the other two (18 and 35% of WAF) showed tumor-promoting activity. The two active portions were then further chromatographed and tested by the short-term bioassay. Some major components of the resulting active fractions included alkyl-2-cyclopenten-2-ol-1-ones, catechols, hydroquinone, fatty acids, and 3-hydroxypyridines. Among these components, catechol, hydroquinone, 3-hydroxypyridine, 6-methyl-3-hydroxypyridine, linolenic acid, and linoleic acid were inactive as tumor promoters in the experimental animal. The activity of the alkyl-2-cyclopenten-2-ol-1-ones is unknown. Other components remain to be identified.

Chicken embryo fibroblasts infected with the nononcogenic herpesvirus of turkeys (HVT) displayed an increased rate of glucose uptake, a pronounced alteration of the pH of the medium, and an increased production of lactic acid when compared to mock-infected cultures. Objective estimates of cytopathology (quantifiable neutral red uptake and cell protein determination) showed that cell deterioration was a slow process in HVT-infected cells when compared to infection by herpes simplex virus. Experiments with irradiated host cells demonstrated that HVT required functional cell DNA for replication. The inactivation of the necessary host cell function displayed multihit kinetics. In agreement with data on other herpesviruses, HVT damaged by UV light could be photoreactivated in chick cells. The results indicate that HVT shares biologic properties in common with other herpes and transforming viruses.

When a 203Ng(NO3)2 solution was kept at 25 degrees C in glass or polypropylene containers, 50 and 80% of original radioactivity was adsorbed to the containers' walls after 1 and 4 days, respectively. However, no loss in radioactivity was observed if the solution was supplemented with HgCl as carrier (100 mug Hg2+/ml) and stored in either container for 13 days. When 203Hg2+ was dissolved in glucose basal salt broth with added carrier, levels of 203Hg2+ in solution (kept in glass) decreased to 80 and 70% of original after 1 and 5 days and decreased even more if stored in polypropylene (60 and 40% of original activity after 1 and 4 days, respectively). In the absence of carrier, decreases of 203Hg2+ activities in media stored in either container were more pronounced due to chemisorption (but) not diffusion. The following factors affecting the removal of mercurials from aqueous solution stored in glass were examined: type and concentration of adsorbent (fiber glass and rubber powder); pH; pretreatment of the rubber; and the form of mercury used. Rubber was equally effective in the adsorption of organic and inorganic mercury. The pH of the aqueous 203Hg2+ solution was not a critical factor in the rate of adsorption of mercury by the rubber. In addition, the effect of soaking the rubber in water for 18 hr did not show any statistical difference when compared with nontreated rubber. It can be concluded that rubber is a very effective adsorbent of mercury and, thus, can be used as a simple method for control of mercury pollution.

The relative ability of arylacetamide deacetylase enzyme systems of dog liver to carry out the deacetylation of the carcinogens, 4-acetylaminobiphenyl, 2-acetylaminofluorene, and 2-acetylaminaphthalene, was examined. The arylacetamides were incubated with unfortified dog liver microsomes, and enzyme activity (nmol arylamine/mg protein/hr) was estimated by colorimetric quantitation of the resulting arylamines. The dog liver enzyme system displayed characteristics similar to those described for the rodent liver enzyme system in that enzyme activity was greatest in liver tissue, was localized in the microsomal subcellular fraction, required no cofactors, and was inhibited by heat, sodium fluoride, and thiol reagents. In five replicate assays, the relative rates of deacetylation were about 10, 6, and 1 with 4-acetylaminobiphenyl (84.8 +/- 12.4), 2-acetylaminofluorene (52.5 +/- 5.1), and 2-acetylaminonaphthalene (8.8 +/- 3.3), respectively. As a canine urinary bladder carcinogen, 4-acetylaminobiphenyl is considered more potent than 2-acetylaminofluroene, while 2-acetylaminonaphthalene is devoid of detectable carcinogenic activity, despite the fact that 2-aminoaphthalene is a well-established canine urinary bladder carcinogen. Removal of the acetyl group may be a requirement for urinary bladder carcinogenesis; accordingly, the present studies demonstrate the appearance of a direct relationship between dog liver deacetylase enzyme specificity and urinary bladder susceptibility to these carcinogenic arylacetamides.

This report is an attempt to study the renal handling of chromium under in vitro conditions and to relate this to the actions of the ion in the production of nephrotoxicity. Renal slice techniques were employed in these studies and were used to examine the effects of chromium on various renal transport processes. In addition, the accumulation of chromium by the renal tissue has also been studied. Marked accumulation by renal cortical slices of the rat was observed when 51Cr-labeled chromate or dichromate was added to the bathing solution. Some metabolic inhibitors interfered with this uptake process; in addition, some substrates metabolized by renal tissue reduced the accumulation of 51Cr. The use of [51Cr] dichromate and [51Cr]-chromate, as well as alterations in the bathing solution pH, indicated that in the rat chromium can interfere with renal transport processes, but that the oxidation state of this metal is not important. On the other hand, in the rabbit a greater interference with 51Cr uptake was noted at lower bathing solution pHs. This is interpreted to mean that chromate is the effective inhibitor in this species.

Arterial pH, Pco2, and osmolality were determined serially during cardiac resuscitation in patients and in dogs, with and without administration of sodium bicarbonate. These studies demonstrate that (1) in the absence of preexisting acidosis, severe acidosis can be prevented by adequate ventilation alone; (2) sodium bicarbonate administration results in a significant rise in arterial Pco2, which parallels the rise in pH despite adequate ventilation; (3) during prolonged cardiac and resuscitation, there is a rise in arterial osmolality that is accentuated by sodium bicarbonate. These studies suggest that sodium bicarbonate should not be used during resuscitation (1) in the absence of effective hyperventilation or where carbon dioxide removal is inadequate despite adequate ventilation, (2) in repeated doses, without confirmation of substantial acidosis, or (3) when cardiac arrest has been of brief duration and preexisting acidosis is unlikely. These studies also point to the need for a reappraisal of other buffers that do not elevate the arterial Pco2.

The membrane site responsible for anomalous rectification was determined in frog sartorius muscle fibers. The total current-voltage relation of glycerol-treated fibers which represents mainly the properties of the sarcolemma was linear for membrane potentials between about -90 and -50 mV. Thus moderate depolarization-induced anomalous rectification in intact fibers represents a property of the sarcotubular system. The absence of slow hyperpolarization in glycerol-treated fibers was caused by the abolition of early conductance increase, and the sarcotubular system is responsible for the inward rectifier. Picrotoxin selectively inhibited both moderate depolarization-induced anomalous rectification and hyperpolarization-induced early conductance increase. This suggests that the same component in the sarcotubular system is responsible for these conductance changes. The inhibition with picrotoxin of moderate depolarization-induced anomalous rectification suggests the possibility that it is caused by an electrogenic effect rather than a decrease in K conductance. A sarcolemmal hyperpolarization-activated slow conductance increase was revealed.

Total current-voltage relations were analyzed on nine glycerol-treated surface fibers of frog sartorius muscles in tetrodotoxin-containing isotonic normal Ringer solution. The results indicate that delayed rectification occurs in the sarcolemma on large depolarization and that delayed rectification is only partially inactivated during 1 sec of depolarization and not converted into anomalous rectification. The time to peak, the time course of inactivation and the potassium activation potential determined in glycerol-treated fibers were comparable to those analyzed previously in intact fibers. The value of the conductance increase during delayed rectification in glycerol-treated fibers appeared to be smaller than that in intact fibers.

The properties of the hyperpolarization-activated sarcolemmal slow conductance increase in frog sartorius muscle fibers have been investigated using ethylenediaminetetraacetic acid disodium salt (EDTA) and propionate Ringer solution. More than 1 sec was required for maximum activation of the sarcolemmal slwo conductance increase. It is suggested that, although the sarcolemmal slow conductance increase was affected by deterioration, the conductance increase is not a direct product of deterioration but it represents a property of the sarcolemma which is encountered in physiological range. The sarcolemmal conductance increase was rather insensitive to the change in pH of Ringer solution. It is inferred that the absence of bellying in newly penetrated intact fibers at neutral and alkaline pHs is caused mainly by the shunting effect of large parallel conductance. Apparent augmentation with EDTA of the sarcolemmal conductance increase infers that Ca ions affect the conductance increase. The conductance increase occurred also in the EDTA-containing Cl-deficient solution. The sarcolemmal slow conductance increase has been compared with the change in Cl conductance reported by Hutter and Warner, and Warner.

Effects of antidepressant drugs on the amygdaloid after-discharge induced by stimulating the amygdala in rats implanted with chronic electrodes, were investigated in correlation with anti-muricidal effects as well as neurotoxicity. Tricyclic antidepressants such as amitriptyline, imipramine and nortriptyline markedly depressed both after-discharge and muricide at doses smaller than neurotoxic doses. The effect of PF-257 was also the same as tricyclic antidepressants. On the other hand, methamphetamine and pipradrol blocked the muricide at doses smaller than neurotoxic doses without depressing the amygdaloid after-discharge. Major tranquilizers, chlorpromazine and clozapine depressed both after-discharge and muricide only at doses larger than those which impaired rotarod performance. Haloperidol, on the contrary, depressed the after-discharge without selectively blocking the muricide. Minor tranquilizers, diazepam and chlordiazepoxide did not block the muricide at doses smaller than neurotoxic doses, although they showed a marked depression of the after-discharge.

Effects of practolol, alprenolol and pindolol on blood pressure in the rat were studied. Also effects of these three beta-blocking agents on blood pressure and heart rate in spinal rats during adrenaline infusion were studied and compared with those of propranolol. The beta-blocking agents produced a sustained pressor action in the rat, and in the spinal rat infused with adrenaline. The magnitude of the pressor action induced by the beta-blockers was in the following order: pindolol larger than or equal to propranolol larger than or equal to alprenolol greater than practolol. Minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline were in the following order; practolol greater than alprenolol larger than or equal to propranolol larger than or equal to pindolol. The magnitude of the pressor action produced by the same dose of these beta-blockers and minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline seemed to be roughly proportional to their beta-receptor blocking activities. It was concluded that the minimum doses of these beta-blockers required to cause a pressor action and the magnitude of the pressor action induced by the beta-blockers in the spinal rat infused with adrenaline could be used to compare their beta-blocking activities and that practolol, a cardioselective beta-blocker, seems to block not only cardiac beta-receptor but to some extent also peripheral vascular beta-receptors.

Dopamine is a direct-acting catecholamine with a short half-life that has many advantages in treating visceral hypoperfusion states such as shock and refractory heart failure. Unlike other inotropic drugs, dopamine directly dilates the mesenteric, renal, and cerebral vessels and redirects blood flow to essential viscera. This dopaminergic effect is prominent with doses of 100-700 mug/min in adults and is attenuated by phenothiazines and haloperidol. At doses of 700-1400 mug/min, dopamine also has a significant beta-adrenergic, inotropic effect, increasing myocardial contractility. The inotropic effect is equivalent to that of isoproterenol, epinephrine, and norepinephrine, but tachycardia, tachyarrhythmias, and angina may be less frequent with dopamine. In doses greater than 1400 mug/min, dopamine is a vasoconstrictor with pressor effects usually equivalent to that of norepinephrine. Dopamine dilates pupils, does not dilate bronchi, and does not shunt blood from viscera to skeletal muscles as does isoproterenol. Because dopamine increases myocardial contractility, selectively redistributes perfusion to essential viscera and allows a pharmacologic titration of effect, it is a logical first-choice catecholamine for treatment of shock and refractory heart failure.

On the basis of extended personal experience and of the literature data, the authors give recommendations for differentiated rational drug therapy of different stages of ischaemic heart disease. The results of a study of comparative efficacy of 15 coronary-active drugs used in 709 patients with ischaemic heart disease are presented along with their clinical pharmacology, side effects, indications and counterindications. The conclusions were arrived at on the basis of an objective clinical and laboratory study of the effect of the drugs. The methods of evaluation of the drug's efficacy and of the selection of patients for the administration of adequate therapy are described, which permits to use these recommendations for practical purposes. Some problems of the pathogenesis of ischaemic heart disease are discussed in terms of the selection of pathogenetic therapy.

The beneficial effect of stimulators of beta-adrenergic structures (Myophedrin on the haemodynamics and the inotropic function of the myocardium was demonstrated experimentally (in 12 rabbits) and clinically (in 53 patients with ischaemic heart disease). A positive effect of the treatment was noted in 45.5% of those patients in whom ischaemic heart disease manifested itself in angina decubitus and angina of effort.

Data on the pharmacology of a new antianginal drug--Nonachlasine--are presented. Nonachlasine was found to increase the blood flow intensively and for long periods of time, increasing the oxygen reserve of the myocardium, thus increasing the cardiac output and the contractile function of the heart. The prevailing action of Nonachlasine on the blood supply and the function of the myocardium seems to be the result of several mechanisms: decreasing resistance of the coronaries due to the activation of the beta2-adrenergic structures; influence upon the extravascular factors of the regulation of the coronary circulation (changes in the metabolism and cardiac activity due to the excitation of the beta-adrenergic structures). The mechanism of the positive effect of Nonachlasine upon the blood supply and function of the heart is connected with its action on the adrenergic processes. The drug accumulates noradrenaline in the myocardium and increases the activity of phosphorilase-a. This coincides in time with the increased blood supply and contractile capacity of the heart. The beta-adrenoblocking agents prevent these effects. It was postulated that the effect of Nonachlasine in the blood supply and the activity of the heart is connected with its ability to utilize the energy reserve of the myocardium by way of switching over to the anaerobic way.

In a double blind study of the clinical effect of Cordaron conducted in 55 patients with chronic ischaemic heart disease a positive effect was obtained in 80.4% of the cases, an effect of placebo-in 24.3%. Cordaron was especially effective in patients with localized stenoses of the coronary arteries. Nonachlasine (an activator of the cardiac beta-adrenergic receptors) proved effective in 10 of 13 patients with chronic ischaemic heart disease.

It has been demonstrated that the study of the activity of 5'-nucleotidase and adenosine-desaminase permits to interpret the metabolism of adenosine. Curanthil, Sustac and Intensain influence the adenosine metabolism favouring an elevation of its content. The therapeutic effect of Obsidan is not conditioned by the "adenosine" metabolism.

This study examines the renal response to moderate hyperventilation in healthy man. Eight men hyperventilated for 26 hr (PaCO2 approximately 30 to 32 mm Hg) in normoxia (barometric pressure, PB approximately 740 mm Hg) and hypobaric hypoxia (PB approximately530 mm Hg). Anaerobic samples of arterial blood and urine were studied at two-hour intervals. Plasma [HCO3-] fell with time during sustained hypocapnia and after 26 hr was reduced 2.5 mEq/liter, with plasma pH compensated approximately 60%. Statistically significant changes in renal H+ handling were observed within the initial 2 hr of hyperventilation and were evident over the first 12 hr. Over 26 hr, mean total HCO3-excretion in hypocapnia was 10.2 mEq above control and mean total acid excretion (UVTA + UVNH4+) was 17.5 mEq below control. An increased urinary excretion of cations, especially sodium, accompanied the decrease in acid excretion. Plasma lactic acid accumulation was negligible. We conclude that renal mechanisms contribute significantly and relatively quickly to plasma pH compensation during the early phase of adaptation to hypocapnia in man.

By animal experiments and clinically we could prove that isoglaucon instillation caused the decrease in IOP due to both increase in outflow and reduction of humor secretion; the IOP decrease and changes in hydrodynamics being manifested more markedly in the fellow-eye. As reoophthalmography demonstrated "Isoglaucon" produced lumen narrowing in the anterior portion of the uveal tract. "Isoglaucon" was prescribed to 20 patients having open-angle-glaucoma, Two hours after instillation the 23 decreased in 26 eyes (of 28) by 9.3 +/- 1.0 mm Hg. When prescribed regularly "Isoglaucon" raised the outflow facility coefficient from 0.10 +/- 0.01 to 0.20 +/-0.02. The secretion decreased from 2.0 +/- 0.2 to 0.9 +/- 0.15. Thus, IOP decrease after "Isoglaucon" is accounted for by both improved outflow and reduction of aqueous humor secretion. The "isoglucon" instillation produced a rather moderate decrease in the total arterial pressure, though no expected parallelism in arterial and intraocular pressure was marked.

In 27 patients with non-compensated or medically compensated chronic simple glaucoma, the I.O.P. was measured after the administration of two tablets of beta-isoket (which contain 5 mg isosorbiddinitrate and 40 mg bupranolol). In none of the 54 eyes was the I.O.P. higher after administration of the drug. On the contrary, the I.O.P. was siginificantly or highly significantly reduced for more than 2 hours, probably because of the beta-receptor-blocking component of the preparation.

By measuring the serum IgM-level every fourth day after keratoplasty the primary immune response can be observed. The extent of the graft's reaction corresponds with the fluctuation of IgM.

The paper describes a semi-closed ecological system consisting of a man and a photosynthetic autotrophic component. The conditions required to maintain the stability of the atmosphere in the system are described as applied to two alternating modes of the function of the autotrophic component. These conditions express equal quantities of oxygen and carbon dioxide consumed and produced by the components of the system during any time period the length of which is the duration of the cycle of the system. On this basis equations have been derived which help to identify the photosynthetic cultures that can be used as an autotrophic component in a closed man-sustaining life support system.

The environmental control system using superoxides, sillicagels or synthetic ceolites is capable of purifying the atmosphere from microorganisms. The air conditioning system is another means for air purification from microorganisms. The possibility of microbial build-up and multiplication in the atmospheric condensate makes it necessary to assume that an air conditioning system may contribute to the transfer of conditionally pathogenic microorganisms in a space cabin. The reliability of a life support system may degrade due to an accumulation of microorganisms in its components. Further extensive studies are needed to clarify this problem.

The experiments carried out on white male rats have shown no significant changes in the animals that may have resulted from their 30-day consumption of reclaimed water which contained up to 34 mg/l methanol and was produced by sorption purification of the atmospheric condensate during a prolonged manned experiment.

The kinetics of the outgassing of volatile substances from polymers of different function and composition was studied with respect to their natural ageing. The outgassing rate was exponentially related to the time of the sample storage. Six to nine months after the polymer fabrication the outgassing rate decreased to a minimum. Possible nobilization of synthetic materials with the aid of diffusion stabilization and thermostatization was investigated. Practical recommendations on how to prevent contamination of the enclosed atmosphere with outgassed products of synthetic materials were developed.

The paper describes a model of an experimental ecological system consisting of autotrophic and heterotrophic components and a nutrient medium. The system has a zero stationary state and needs a correction. The life time of the system and the level of the necessary correction have been determined for the experimental ecological system: lettuce - slugs - nutrient solution. Optimal conditions for the conjugation of trophic components of the system have been established.

Control of mineral nutrition of higher plants is one of the problems involved in the development of life support systems. The experiments on carrots cultivated aeroponically have demonstrated that mineral nutrition of plants can be controlled by means of a correction solution applied in accordance with the protocols derived from experimental studies of increase in the plant dry biomass.

The literature data concerning the effect of the atmosphere composition on the photosynthetic productivity of an intensive microalgal culture were used to build a mathematical model of a semiclosed ecological system working in the light-dark alternating cycles. The type of the relationship between time cycles and composition of the stationary atmosphere of the ecological system has been established. The conditions of the existence and stability of the stationary atmosphere have been determined.

In this paper the comparative evaluation of the results of the surgical and conservative treatment applied in patients with Perthes-Legg-Calvé disease is given. The results obtained with intertrochanteric femur osteotomy performed in 39 patients and those obtained in 66 patients with conservative treatment are reported. The results are evaluated from the point of view of the patients' age, the localization of the process and the stages of the disease. The surgical treatment brought about in 1/3 of the cases excellent-in 1/3 good - and in 1/3 unsatisfactory results. Int the group of patients who received conservative treatment 1/3 of the cases showed excellent - 1/5 of the cases good - and 3/5 of the cases unsatisfactory results. The advantage of the surgicat treatment is that the patients are not confined to bed for long time and they must nol use walking splint releasing the hip-joint.

The increasing number of respiratory insufficiency, as well as of pulmonary complications after burns and their role in the post-traumatic mortality are pointed out by the author. The pathophysiological processes responsible for the development of post-traumatic pulmonary complications are shortly resumed. In respect of the clinical picture, three groups are distinguished by the author. One case is reported in detail. In the development of post-traumatic respiratory insufficiency important role is attributed by the author to the syndromes of micro-embolism. This supposition is supported by the laboratory examination of 10 patients. Finally the problems of prevention and therapy are discussed and the importance of the iatrogenic damages is emphasized.

The management of burns consists essentially of the surgical removal of the necrotic skin layers and the substitution of the skin defects. Secondary skin transplantation does not prevent completely the cicatrization and all complications of the burn. The management of burns is partially classed among the problems of the conservative therapy. Early excision excludes the danger of demarcation and infection, and immediate transplantation may prevent the destruction of the subcutaneous skin layers. This advantages are assured in the cases concomitant with partial necrosis by xenotransplantation.

The surgeon assuming the task of reconstruction of burned face must be skilled in plastic surgery. Primary surgical treatment and reconstruction are inseparable, therefore it is desirable that the treatment is performed since the day of the injury to the completion of the reconstruction by the same surgeon. In the surgical management of the facial burns relative conservatism is advisable. The excision is to be performed after the recovery of the second-degree burned areas. The above-mentioned principles are documented by the author on the basis of a few cases.

The number of the injuries and of the open fractures is steadily increasing. These latter are regularly due to traffic accidents. Characteristics of the open fractures are the extended lesion of the soft parts and the piece-like fractures. The treatmend depends on the patient's general state, the extension of the lesion of the soft parts, the contamination and the infection of the wound, as well as on the localization and the type of the fracture. In the case of proper indication the osteosynthesis yields satisfactory results, but it is not always to be performed and its use to exposed to dangers. The conservative treatment assures good results, if the lesion of the soft parts is minimal, the reduction of the dislocation is easily accoplished and the bone ends are to be held together. On the other hand, the method is unsuitable, if extended lesion of the soft parts occurs, as well as in the treatment of multifragmental fractures. In this group of the open fractures we must try to find other, new methods.

On the basis of 7 years' material, the distribution of 73 foreign bodies - of non-metallic intensity - in the hand and the foot is discussed. The foreign bodies did not appear as new, fresh lesions, but they have been diagnosed after longer or shorter symptom-free state. In the case of fistulous process immediate removal has been performed, and in the case of closed cases - on the basis of the clinical picture - immediate removal - or removal after fixation for a few days was effective. In the author's opinion, fixation is - so long as acute symptoms are present - in all cases indispensable, - fixation is immediately followed by physicotherapy, in order to assure good functional results.

In open fractures of the leg, in which because of any reason no primary stable osteosynthesis can be performed, threading with Kirschner wire is preferred by the authors. This method assures adaptation stability, with minimal osteosynthesis. Primary closure of the wound in the soft parts is striven by the authors, - if necessary, even by plastic surgery. If primary healing of the wound is obtained and also the other conditions are favourable, the treatment after 7-10 days is the same as after covered fractures: stable osteosynthesis is performed. On the other hand, if suppuration of the wound occurs, the opposing fixed fracutre bone ends assure favourable conditions for the successful surgical treatment of the fracture. A further advantage of the method is that it may be performed without special instruments and without greater surgical experience. The results obtained with this surgical treatment of open leg fractures in the 4 years' material of the Traumatological Department of the First Surgical Clinique of the University Medical School, Pécs, are discussed by the authors.

In respect of iatrogenic infections the elderly patients are to be considered as endangered. Modern traumatology increases this danger in consequence of the foreign materials placed in the wounds. The role of the antibiotic and chemotherapeutic prophylaxis is of utmost importance. Regrettably, the resistance of the pyogenics, especially of the strains in the hospitals is increasing, - in consequence, besides the maximal sterility the further improvement of the surgical technique and of the after-treatment are the most important tasks. In the case of infection aimed antibiotic and chemotherapeutic, resp., treatment may be successful.

The nowadays accepted principles of the treament of open leg fractures are discussed. The open character of the lesion multiplies the possibilities of complications. In the present paper the complications of the bone recovery are not dealt with, only the complications observed in the soft parts and the possibilities of their treatment are analysed by the authors. According to the severity of the soft parts complications free transplantation of semi-thick skin, pedicle flap plasty, double-end graft plasty, crossed flap grafting, as well as the primary and secondary variations of these methods are used by the authors. The satisfactory results obtained with these methods even in spite of the complications are pointed out by the authors.

Open leg fractures observed in 81 patients are analysed by the authors. In case of conservative treatment alone and in the group, which has been treated with primary osteosynthesis satisfactory results have been observed by the authors. False joint and osteomyelitis happened only in the group, in which the patients obtained firstly conservative treatment and in the case of the failure of this treatment osteosynthesis has been carried out. In the authors' opinion the most frequent complications are due - besides the damage of the soft parts - to the repeated and sometimes erroneous interventions.

The surgical treatment of a severe injury in the cubital region of a bus-driver, aged 47, is reported. Because of the extended contamination and the splintered fracture radical wound excision - involving also the chondral surfaces - has been performed and hereupon humero-radial arthrodesis was carried out. The skin defect has been successfully treated secondarily by insert of a flap. After uneventful recovery the patient could resume his work 6 months after the injury again.

The injury due to burns embraces three, nearly concentric zones. The necrobiosis of the central and marginal zones is reversible and the pig-skin - assuring biological ligature - plays important role in turning for better of the process. The preparation and use of Xenograft - applied in the author's department - is discussed.

Mosquito-borne arboviruses are prevalent throughout subarctic regions of Canada and Alaska, principally in the boreal forest extending between latitudes 53 and 66 degrees N, but they have been identified in tundra regions as far north as 70 degrees N. All mosquito-borne agents have been bunyaviruses, comprising principally the snowshoe hare subtype of California encephalitis (CE) virus, but also Northway virus. Mosquito vectors comprise several Aedes species and Culiseta inornata, all of which have supported replication of CE virus following incubation at 13 degrees C or lower temperatures. Isolation of virus from wild-caught larvae points towards transovarial transfer. Principal vertebrate reservoirs of infection are mammals, especially snowshoe hares (Lepus americanus) and ground squirrels (Citellus undulatus). Where the boreal forest merges into prairie grassland around 53 degrees N, Culex tarsalis mosquitoes become prevalent, and an alphavirus, western equine encephalomyelitis, is detected more frequently than CE virus.

Mosquito longevity and blood-feeding behaviour are very important but neglected factors in the dynamics of arbovirus infections as changes in them affect transmission rates exponentially. Some mosquito species feed on a narrow range of vertebrates, some on a wide range, both influenced by host-availability and other environmental and behavioural factors. Only those which feed on maintenance hosts contribute to maintenance of the infection. Some species change their feeding pattern with season. The frequency of blood-feeding depends inter alia on environmental temperature. Longevity is perhaps most important: the majority of mosquitoes infected probably do not survive long enough to become infective; it is influenced by relative humidity, temperature and predation. Longevity, feeding frequency and the extrinsic incubation period are all temperature dependent and are therefore important rate determinants in seasonal epizootics or epidemics. Equally, their relative stability in the tropics contributes to the equilibrium of an enzootic or endemic.

The nucleocapsid of the Semliki Forest virus is composed of 34% RNA and 66% protein, or one RNA and about 240 capsid protein molecules. The particle is spherical, with a diameter of 38--39 nm. If the nucleocapsid is exposed to slightly acid pH (6.4--5.6) it undergoes a structural change and is contracted to a 32 nm state. A similar contraction can be effected by RNase treatment, in this case, however, in connection with a loss of RNA. Treatment of the nucleocapsid with 0.2 mM SDS results in dissociation of capsid protein from RNA, an effect which suggests strong RNA-protein interaction. At 0.05 mM SDS the protein remains associated with the RNA, but the S-value is reduced from 150 S to 100 S. Electron micrographs of the 100 S ribonucleoprotein showed irregular and strand-like structures.

The present data show that SPN have a striking influence on thymus dependent T cells. The enhancing effect of gvh reactions on antibody formation against thymus dependent antigens give a good explanation for the antitumor effects of this substance.

The morphology and function of the urethrovesical junction are described to give some understanding of the pathogenesis and therapy of female stress incontinence. Conservative procedures can only be helpful in stage-1 stress incontinence, whereas in stage 2 surgical treatment provides excellent results.

The activity of pyruvate dehydrogenase from freshly isolated mitochondria was shown to be dependent upon the nutritional and metabolic state of the animal prior to sacrifice, such that mitochondria from the livers of 48 hr starved, diabetic, or high fat fed rats had lower enzyme activity than normal, chow fed rats. The activity of pyruvate dehydrogenase and the rate of lipogenesis were shown to correlate to a certain extent when a reconstituted, cell free system consisting of 105,000 x g supernatant of rat liver and isolated mitochondria was used. This system was employed so that the role of the mitochondrion and pyruvate dehydrogenase in lipogenesis could be investigated. Dichloroacetate increased the activity of pyruvate dehydrogenase and increased the rate of lipogenesis, suggesting that the activity of pyruvate dehydrogenase is an important factor in determining the rate of lipogenesis in the reconstituted system. It was observed, however, that dichloroacetate was more effective in stimulating the activity of pyruvate dehydrogenase than the rate of lipogenesis when mitochondria from starved animals were used to reconstitute lipogenesis. Furthermore, the cytoplasmic adenosine triphosphate/adenosine diphosphate ratios and phosphorylation potentials (ATP/ADP x Pi) maintained in the reconstituted system by mitochondria isolated from starved animals were found to be significantly lower than those maintained by mitochondria isolated from chow fed animals. It is proposed that the lower "energy pressure" maintained in the reconstituted system by mitochondria isolated from starved animals severely limits lipogenesis at the ATP requiring steps of the process.

Testicular tissue was shown to contain the full complement of enzymes required for de novo synthesis of fatty acids. The enzymes capable of snythesizing palmitic acid from citrate, acetate, or acetyl CoA were found to be present in the soluble (cytoplasmic) fraction. These included fatty acid synthetase, acetyl CoA carboxylase, citrate-cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. Optimal conditions for assaying activities of fatty acid synthetase and acetyl CoA carboxylase in the soluble fraction from rat testes were established, and the activities of these two enzymes were determined to be 0.54 +/- 0.1 and 0.030 +/- 0.002 (nmoles of substrate incorporated into fatty acid per min per mg of soluble fraction protein), respectively. The activities of citrate-cleavage enzyme, malic enzyme, and the glucose-6-phosphate dehydrogenase/6-phosphogluconate dehydrogenase pair were also measured. The activities were 6.0 +/- 0.7, 34.9 +/- 4.2, and 29.9 +/- 9.3 nmoles/min/mg, respectively.

An in vitro system for acetate incorporation into fatty acids by the mitochondrial and the cytosol fractions of rat testis is described. The rate of incorporation of acetate into fatty acids was twice as fast with the mitochondrial as with the cytosol fraction; both systems were stimulated in the presence of adenosine triphosphate, reduced nicotinamide adenine dinucleotide phosphate, coenzyme A, and MgC1(2). The optimum pH was between 7.0-7.5 for the mitochondrial fraction and between 6.5-8.0 for the cytosol fraction. Radio gas chromatography showed that palmitic acid was the most highly labeled acid, followed by stearic acid, in the mitochondrial fraction in accord with the pathway of de novo fatty acid synthesis. Some of the labeled acetate was also incorporated into the 16:1 and 18:1 fatty acids of this fraction. Distribution of radioactivity among the mitochondrial lipid classes was highest in the phospholipids and monoglycerides, followed by diglycerides and cholesterol; little radioactivity was present in the triglyceride fraction. These observations are in accord with studies of the incorporation of labeled metabolites into testicular lipids following intratesticular injection and indicate the validity of the in vitro system for studies of specific reactions occurring in vivo.

Cell free preparations of avocado mesocarp and spinach leaf tissue rapidly convert lauryl CoA to DL-3-hydroxyl lauric acid as well as 2-, and 3-dodecanoic acids. The conversion does not occur under anaerobic conditions unless a suitable redox carrier such as ferredoxin is present. H2 18O is incorporated into the 3-hydroxyl function, but O2(18) is not. The characteristics of this system are presented and a possible function of this system is proposed.

Transplantable mammary adenocarcinomas and livers of C3H mice fed a stock diet or a linoleate rich diet (15% corn oil) contain similar amounts of oleate (ca 3 mg/gm tissue). On feeding either a high carbohydrate, fat free or a high carbohydrate, saturated fat-containing (15% hydrogenated coconut or cottonseed oil) diet for 6 weeks, oleate levels increased 2-fold in tumor and 5-fold in liver. The specific activity of stearoyl-CoA desaturase in liver microsomes was similar to that in the corresponding fractions of mammary glands of lactating mice. In liver, this activity was enhanced 2- to 3-fold by feeding a high carbohydrate, fat free or a high carbohydrate, saturated fat diet. The desaturase activity in mammary tumor microsomes, while only 10% of that in hepatic microsomes, remained unaltered regardless of the type of diet fed. These observations suggest that (a) a major portion of the oleate in the mammary tumor is not produced within the tissue, (b) dietary adaptation is not a general characteristic of stearoyl-CoA desaturase in neoplastic tissues, and (c) enhanced desaturase activity in liver is directly related to the absence of linoleate or oleate, or to a large decrease in oleate in the diet.

During the 1973 and 1974 state high school wrestling championships, urine samples were obtained from wrestlers prior to the weigh-in, immediately before they wrestled, and immediately after the subjects had completed their match. Specific gravity, osmolarity, pH, sodium and potassium determinations, as well as qualitative tests for protein and ketones, indicated that the wrestlers were in a dehydrated state at the time of weigh-in. After the five hour interim between the weigh-in and the first match, all but the pH measure remained essentially unchanged. This absence of significant changes in the urinary profile suggests that the wrestlers were unable to rehydrate during the five hour time period between the weigh-in and the first match and that they were competing in a dehydrated state. Urine samples collected after competition were significantly lower in specific gravity, osmolarity and potassium concentration than samples obtained before the match. The urinary potassium levels were of interest because at the three conditions (weigh-in, before the first match, after competition) they were 73-182% higher than values reported for high school students who were nonwrestlers.

The development of generalized necrotizing vasculitis in association with hepatitis B antigenemia is the first example in man of a chronic rheumatic disease presumably caused by a viral infection. This report reviews the experience in nine biopsy-proven cases of hepatitis B-associated necrotizing vasculitis followed for up to six years. The natural history of the disease is emphasized and the manifestations of patients with vasculitis who carry hepatitis B antigen are compared with those of vasculitis patients who are antigen negative.

An association between viral hepatitis and two rheumatic disease syndromes has been observed. Twenty-nine patients manifested a transient polyarthritis, sometimes associated with a rash (Group I). Ten patients were seen with a multisystem disease (Group II). Histologic evidence of arteritis or glomerulonephritis was present in seven of ten patients with multisystem disease. Liver tissue from 18 patients showed morphologic evidence of hepatitis with viral features in 9 of 10 patients in Group I and in 6 of 8 patients in Group II. Hepatitis B surface antigen (HBsAg) and/or antibody to HBsAg were detected in sera of all 39 patients. Abnormal liver functions were present in 36. Twelve Group I patients and 2 Group II patients became jaundiced. Rheumatoid factor was present in sera of seven patients in each group. The third component of complement (C3) was depressed in 13 patients in Group I and 7 patients in Group II. The fourth component of complement (C4) was decreased in 8 of 21 Group I and 3 of 7 Group II patients. Synovial fluid C3 was decreased in 2 of 11 Group I and 1 of 4 Group II patient's fluids. Articular inflammation in patients with transient polyarthritis responded in three to seven days to aspirin, acetominophen and/or bedrest alone and rashes disappeared spontaneously. Patients with multisystem disease generally had a prolonged illness and responded somewhat unpredictably to prednisone or a combination of prednisone and cyclophosphamide.

In healthy male subjects aldosterone excretion and plasma renin activity were reduced by a 4-6 hr head-out immersion in thermoindifferent water baths (35.5 +/- 0.1 degrees C). The red cell 2,3-diphosphoglycerate (DPG) concentration before and throughout immersion period was positively correlated both with aldosterone excretion in 2 hr pooled urine (r = +0.69; 2 p less than 0.001) and with renin activity (r = + 0.54; 2p less than 0.001) despite a concomitant increase of cubital venous pH and inorganic phosphate concentration. These findings furnish evidence for a regulatory role of aldosterone in DPG metabolism, possibily by a direct influence on red cell glycolysis.

Rhodopseudomonas palustris, Rh. viridis, Rh. acidophila, and Rhodomicrobium vanniellii grow on media containing ethanol, n-propanol, and n-butanol. The highest amount of lower alcohols is utilized by the strains of Rh. palustris. Only Rh. acidophila accumulates methanol. Alcohol dehydrogenase of Rh. palustris, Rh. viridis, and Rhodospirillum rubrum requires for its activity NAD, that of Rhodomicrobium vanniellii--NADP, and the enzyme of Rh. acidophila is active in the presence of phenazine metasulphate (PMS) and ammonium ions. Aldehyde dehydrogenase from two strains of Rh. palustris also requires NAD; the Nakamura strain is active in the presence of PMS. Aldehyde dehydrogenase of Rh. acidophila is active in the presence of PMS and ammonium ions. Different bacterial species vary in the substrate specificity of their alcohol dehydrogenases.

Mycobacterium lacticolum 121 grows and synthesizes exopolysaccharide at the initial values of pH of the medium from 5.0 to 11.5. The accumulation of biomass is maximal (10 to 12 gram/litre) at pH 6.0 to 11.5; the rate of growth is highest at pH 8.0 to 11.5. The largest amount of exopolysaccharide (2.0 to 2.4 gram/litre) is produced in the medium at pH 8.0 to 11.0; the rate of its production is highest at pH 9.0 to 11.0. The growth of Mycobacterium lacticolum 121 and the biosynthesis of polysaccharide are optimal at pH 8.0 to 8.2. Changes in acidity of the medium have no effect on the qualitative composition, structure, and molecular weight of the polysaccharide.

The growth of Pseudomonas methanolica was inhibited by unfavourable values of pH in the conditions of chemostat; the rate of the substrate assimilation was higher, and anabolic and catabolic reactions were decoupled. Hydrogen ions inhibited the activity of enzymes of the Krebs cycle, hydroxyl ions inhibited the activity of methanol dehydrogenase. Changes in pH are presumed to involve the energy apparatus of the cell membrane.

The lysis of Actinomyces rimosus producing oxytetracycline during its mass growth can be caused by two factors which were separated by differential centrifugation. The first factor is phage particles of a temperate phage produced by the culture; they are incapable of growth but may induce the lysis. The phage particles treated with low pH and a temperature of 70 degrees C lose the lytic activity. The second factor is a lytic enzyme produced under the control of the temperate phage during its induction; it seems to consist of at least two enzymes, a lytic enzyme and a proteolytic enzyme.

Pulmonary artery and pulmonary wedge pressures were measured at rest and during exercise in 25 young patients with moderate to severe scoliosis. Simultaneous determinations of arterial blood gases and pH were performed. The results of the vascular pressure measurements were compared with those obtained in 15 healthy young subjects. In all patients the pulmonary artery and pulmonary wedge pressure were normal at rest. During mild ergometer exercise, however, an abnormal rise in pulmonary artery pressure occurred in 9 patients. Moreover, an increased diastolic pressure gradient across the pulmonary vascular bed was found in some scoliotic patients indicating an elevated pulmonary vascular resistance. It is supposed that this haemodynamic abnormality is primarily due to a restriction of the pulmonary vascular bed. Relationships between pulmonary artery pressure and arterial oxygen tension and blood pH, respectively, could be found. The possible significance of these results is discussed.

Report dealing with the clinical and pathoanatomical course as well as the autopsy findings in a 54 year old female suffering from panarteritis nodosa. Onset of the illness with polyneuritis and arthralgia. One year later diagnosis of panarteritis nodosa verified by muscle biopsy. Deterioration of the disease leading to the development of peripheral gangrene could not be prevented in spite of intensive therapy with steroids, immune suppressive agents, digitalis and antihypertensive drugs. Death 4 years later by myocardial infarction. Autopsy revealed generalized healed panarteritis nodosa with scarring and obliteration of vessels. A short description of the symptoms of the disease is given and the efficacy of the therapy with steroids and immune suppressive drugs is discussed from the clinical as well as the pathoanatomical point of view. Immunopathologic mechanisms are considered to be the responsible factors for pathogenesis.

We studied the relative importance of hyperkalemia and mineralocorticoid deficiency in the metabolic acidosis of a patient with proved isolated hyporeninemic hypoaldosteronism and moderate kidney failure. The hyperkalemia and acidosis were severe in relation to the slight azotemia. Despite the systemic acidosis and urinary pH of 4.9, urinary ammonium excretion was distinctly blunted. Correction of the hyperkalemia by potassium-sodium exchange resin alone resolved the acidosis and restored the previously diminished urinary ammonium excretion to normal. Administration of mineralocorticoids only partially corrected the hyperkalemia and the acidosis. Hyperkalemia by itself, rather than hypoaldosteronism per se, caused the acidosis in this patient. Hyperkalemia apparently suppresses urinary ammonium excretion and thus interferes with urinary acidification.

Penicillium corylophilium Dieckx was isolated from sludge collected at the interface of an aqueous, copper-bearing leachate and an organic, kerosene based, ion exchange solvent. The organism assimilated kerosene and various straight chain and cyclic hydrocarbons including dodecane, hexadecane, octadecane, toluene, benzene, and cyclohexane. Assimilation of kerosene and hexadecane was optimal at pH 2 and was stimulated by yeast extract.

Chitinolytic microorganisms isolated from forest soil and from healthy gypsy moth larvae (Porthetria dispar (L.) were screened for their ability to lyse Trichophyton rubrum mycelia. A few of these isolates were mycolytic on both autoclaved and on actively growing, intact, T. rubrum mycelia. Supernatants from these isolates, utilizing live T. rubrum as the sole carbon source, showed the same mycolytic ability. Assays of the supernatants for enzymatic activity revealed exocellular, stable enzymes that releases reducing substances including N-acetylglucosamine from the mycelia.

A model catalyst is described which has properties in common with carbonic anhydrase. The model demonstrates the availability of a mechanism, previously only hypothetical, for the action of the enzyme. It also shows, however, that this mechanism alone is not adequate to produce the high activity of the enzyme.

Studies were made of the mechanisms regulating the quantity and catalytic efficiency of hepatic acetyl coenzyme A carboxylase, which plays a critical role in the control of fatty acid biosynthesis. The microsomal enzyme system responsible for the formation of phosphatidic acid, the initial step in glycerolipid biosynthesis, was resolved into two component enzymes. The acyl-donor specificities of these and other acyltransferases account for the asymmetric fatty acid distribution in naturally occurring glycerolipids.

Strains of transmissible gastroenteritis (TGE) virus possessing different pathogenicity were examined for stability to digestive enzymes and acid, and growth at various temperatures. In growth experiments, virus titer obtained at 37 degrees C were about equal between attenuated and virulent strains, but titers attained by the attenuated strain were higher at 30 degrees C. The attenuated virus multiplied at 28 degrees C, but the virulent virus did not at this temperature. The virulent virus was significantly stable to trypsin and pepsin, but the attenuated virus was inactivated rapidly by these proteolytic enzymes. No significant differences were observed in stability to acid between the attenuated and virulent strains. At different pH, both lost their infectivity more rapidly at 37 degrees C than at 22 degrees C.

The established hamster lung cell line, HmLu-1 cells could grow in a suspended state. The initial cell count, 40 X 10(4)/ml, increased to 200 X 10(4)/ml on the 4th day of culture. The suspension culture of HmLu-1 cells was proved satisfactory for propagation of Ibaraki virus. The viral titer reached a maximum of 10(6.75) TCID50/0.1 ml. The input multiplicity ranging from 0.003 to 3.0 exerted no influence on the final yield of the virus. The optimal pH value of initial culture ranged from 6.8 to 7.6. In comparison of virus yield per cell among the suspension culture and two methods of monolayer culture in stationary and rolling condition, there was no noticeable difference in it among the three methods. The cell population per unit volume was the largest and, therefore, virus titer in the culture fluid the highest in the suspension culture of the three methods.