On the nature of basal vascular tone in cat skeletal muscle and its dependence on transmural pressure stimuli. The aim of the present study was to elucidate in some detail the characteristics of the intrinsic basal vascular tone in the adrenergically blocked skeletal muscle with regard to its extent and site along the vascular bed, its dependence on arterial pressure via static and dynamic transmural pressure stimuli, and its sensitivity to local metabolic influence. Basal tone, which apparently is of myogenic nature, was pronounced in 'proximal arterial vessels' (greater than 25 mmicrometer i.d.) and in the 'microvessels' (less than 25 micrometers), but low in 'large veins'. Its functional characteristics, however, were different in the 'proximal arterial vessels' and the 'microvessels'. Normal basal tone in the 'microvessels' thus seemed to be intimately dependent on the arterial blood pressure level and, at least partly, initiated by its static mean pressure distension effect as well as by its dynamic pulse pressure oscillations. It could be virtually abolished by a transmural pressure decrease applied at fast rate ('strong inhibitory dynamic transmural pressure stimulus'). Basal tone in the 'proximal arterial vessels', on the other hand, was little affected by arterial pressure and almost irresponsive to transmural pressure stimuli. Basal tone in the 'microvessels' was much more sensitive to metabolic stimuli than that in the 'proximal arterial vessels'. The present results, viewed in the light of some recent electrophysiological studies on vascular smooth muscle, suggest that smooth muscle in the 'microvessels' is mainly of the spike-generating type, whereas that in the 'proximal arterial vessels' seems to be of different nature, possibly of the non-spike-generating type.


B.K. virus haemagglutinin.

B.K. virus haemagglutinin. Among the widely applied buffered media, the HSAG (hepes-salt-albumin-gelatin) medium at pH 5.75--6.25 was found to be the most favourable for B.K. virus haemagglutinin titration. The optimum temperature was at 4 degrees C. The haemagglutinin was not affected by temperatures up to 37 degrees C, pHs between 5.5 and 9.5, and NaCl concentrations between 0.063 M and 2.56 M. When incubated at 56 degrees C, the haemagglutinin shows a time and pH dependent decline in titre. No significant time dependent titre fall occurred at 56 degrees C if NaCl molarity was varied between 1.31 and 2.56.


A rhabdovirus isolated from carps in Hungary. Experimental infection of carps and resistance of the virus. From carps showing the symptoms of acute infectious dropsy, a virus was isolated for the first time in Hungary. On the basis of physicochemical and serological tests and electron  microscopy, the virus was identified as spring viraemia carp virus and assumed to have a primary role in the acute form of infectious dropsy known so far as a bacterial disease.


Acupuncture and gastric acid studies.

Acupuncture and gastric acid studies. The effects of therapeutic acupuncture on gastric acid secretion on pain relief in chronic duodenal ulcer patients were studied. Ten adult Nigerian patients with clinical, endoscopic as well as radiological evidence of duodenal ulcer constituted the "Ulcer Group." Four other patients who gave history of dyspepsia formed the "Dyspeptic Group." Pentagastrin stimulation test was performed on all subjects pre- and post-acupuncture therapy. The classical Chinese acupuncture loci were employed. The mean Basal Acid Output (BAO) in the duodenal ulcer group was markedly reduced from 4.04 +/- 1.01 mMols/hour to 1.05 +/- 2.5 mMols/hour. The mean Maximal Acid Output (MAO) was lowered from 34.72 +/- 13.81 mMols/hour to 15.34 +/- 4.01 mMols/hour. The difference was statistically significant (P less than 0.001). It is more probable, therefore, that the relief of pain is attributable to the therapeutic inhibition of gastric hyperacidity in our patients. Thus, though pain relief has been previously demonstrated in response to acupuncture, the results of this investigation have gone further to show that acupunture achieves symptomatic relief through therapeutic gastric depression in duodenal ulcer patients.


Toxin production by Clostridium botulinum in grass. Investigations on farms where botulism has occurred in cows showed that proteolytic Clostridium botulinum type B was present in newly made grass silages. Experiments were undertaken to study growth and toxin production of C. botulinum in grass. Of the strains tested only proteolytic strains of C. botulinum types A and B were able to produce toxin with grass as a substrate. Proteolytic strains of type B produced both medium (12S) and large (16S) toxin forms. The minimal water activity (aw) for toxin production at pH 6.5 and 5.8 was 0.94. At pH 5.3, toxin was produced at an aw of 0.985. These results indicate that proteolytic strains of C. botulinum (if present) may multiply and produce toxin in wilted grass silages.


Heat inactivation of Mycobacterium avium-Mycobacterium intracellulare complex organisms in aqueous suspension. Isolants from swine and from humans representing serotypes 1, 2, 4, 8, and 10 of the Mycobacterium avium-Mycobacterium intracellulare complex were compared for heat tolerance in aqueous suspension. The most heat-resistant isolant found was a serovar 10 isolated from a human. This isolant was examined further to determine the rate of kill at various temperatures and pH's, the effect of meat protein and fat, and the effect of nitrite. Kill rates were not significant at 60 degrees C or below. Decimal reduction values were 4 min or less at 65 degrees C and 1.5 min or less at 70 degrees C. Kill rates were slightly higher at pH values of 6.5 and 7.0 than at 5.5 or 6.0. the water-soluble fraction of wiener emulsion did not alter kill rates, but the saline-soluble fraction protected the organism somewhat. Fat did not affect the survival of the organisms except to eliminate the protective effect of saline extract when the suspension contained 50% fat. The addition of sodium nitrite to the suspension did not alter the heat sensitivity of the organisms.


Effect of processing variables on the outgrowth of Clostridium sporogenes PA 3679 spores in comminuted meat cured with sorbic acid and sodium nitrite. The effects of the initial pH and a "short pump" on the outgrowth of Clostridium sporogenes PA 3679 spores in comminuted cured pork were studied. Fresh ground pork was cured with salt, sugar, phosphate, ascorbate, and varying amounts of sodium nitrite and sorbic acid. The product was comminuted and inoculated with 1,000 spores of C. sporogenes per g. The meat was stuffed into 1-ounce (ca. 28.4-g) aluminum tubes, cooked to 58.5 degrees C, cooled, and incubated at 27 degrees C to observe for swells. Product cured with 0.2% sorbic acid in combination with 40 ppm sodium nitrite (40 microgram/g) had better clostridium inhibition than did product cured with 120 ppm nitrite within a pH range of 5.0 to 6.7. The sorbic acid-40 ppm nitrite combination also gave better clostridial protection than did the 120 ppm nitrite alone when reduced amounts of curing ingredients were present.


N-demethylation of lergotrile by Streptomyces platensis. Thirty-eight microorganisms were screened for their ability to produce metabolites of the semisynthetic alkaloid, lergotrile. A total of five microorganisms were found to biotransform lergotrile, and N-desmethyl lergotrile was detected as the principal metabolite with most organisms. Streptomyces platensis (NRRL 2364) appeared to form the metabolite in highest yield, and a preparative-scale conversion was accomplished with a recovered yield of 50%. Structure proof was accomplished with comparative thin-layer chromatography, mixed melting point, mass spectrometry, and remethylation to lergotrile.


Viral aggregation: mixed suspensions of poliovirus and reovirus. The aggregation of mixtures of two dissimilar viruses, poliovirus I (Mahoney) and reovirus III (Dearing), was followed by electron microscopy under conditions known to induce either aggregation or dispersion of each virus separately. Neither virus aggregated at pH 7 in an appropriate buffer, and no mixed aggregates were formed. Under conditions of lowered ionic strength (by dilution into distilled water) poliovirus became aggregated, whereas reovirus did not, and again no mixed aggregates were formed. At pH 6, however, poliovirus again aggregated and, although reovirus did not, it attached to poliovirus aggregates. Thus, some inducement toward aggregation was necessary to cause formation of mixed aggregates. This inducement probably took the form of a reduction of the ionic double layer surrounding the particles, which is known to occur at low pH. At pH 5 and below both viruses aggregated severely, and large mixed aggregates were formed. These mixed aggregates could be broken up by neutralization of the suspension, although small aggregates of poliovirus remained. Reovirus showed a marked tendency to attach to large clumps of poliovirus, but the reverse tendency was not observed. The results indicate that mixed aggregates may be of significance in the isolation of viruses from water or wastewater.


A further study on antihypertensive action of beta-adrenoceptor blocking agents in conscious, renal hypertensive dogs. Experiments were carried out on 7 conscious, renal hypertensive dogs with 7 beta-adrenoceptor blocking agents (atenolol, bunitrolol, bunolol, carteolol, nadolol, sotalol and timolol). Three main conclusions may be made from this study: (1) the stronger the beta-adrenoceptor blocking activity the stronger the antihypertensive action; (2) for the antihypertensive action, very strong beta-adrenoceptor blocking activity was needed; (3) d-carteolol, unlike dl-carteolol, had no antihypertensive effect. Thus, the beta-adrenoceptor blocking action per se is a prerequisite for the antihypertensive effect of the beta-adrenoceptor blocking agents.


An in vivo model for investigating alpha 1- and alpha 2-receptors in the CNS: studies with mianserin. Locomotor activity in rats was reduced by intracisternal (i.cis.) injection of the selective alpha 2-agonist clonidine and increased by the i.cis. administration of the selective alpha 1-agonists phenylephrine and methoxamine. These responses to i.cis. administered clonidine, phenylephrine and methoxamine were examined in rats pretreated subcutaneously (s.c.) with various alpha-adrenoceptor antagonists believed to exhibit preference for alpha 2- or alpha 1-receptors in peripheral tissues. At a dose that eliminated the locomotor depressant effect of clonidine, the alpha 2 -antagonist yohimbine did not antagonize the locomotor stimulant effects of phenylephrine and methoxamine. Similar results were obtained in animals pretreated with another alpha 2-antagonist piperoxane. The alpha 1-antagonist prazosin abolished the increase in motor activity elicited by phenylephrine and methoxamine, but at the same dose prazosin did not offset the decrease in motor activity caused by clonidine. The alpha 1-antagonist azapetine, at a dose that inhibited the increase in motor activity elicited by phenylephrine, was without effect on the decrease in activity produced by clonidine. These findings indicate that the locomotor responses to the alpha 2-agonist clonidine and the alpha 1-agonist phenylephrine (or methoxamine) can be used for determining whether or not a particular substance acts in vivo as a selective antagonist for alpha 1- or alpha 2-receptors in the CNS. In rats pretreated s.c. with 13.5 mg/kg of mianserin, the locomotor depressant effect of clonidine and stimulant action of phenylephrine were unchanged. At 27 mg/kg s.c., mianserin antagonized the responses to both clonidine and phenylephrine. Therefore, in this in vivo model system, mianserin given systemically did not display any appreciable selectivity for blocking alpha 1- or alpha 2-receptors in the CNS.


Potentiation by D-penicillamine and other sulfhydryl agents of the vascular response to histamine in the anaesthetized dog. D-penicillamine (80 mg/kg) potentiates the fall in blood pressure produced by an i.v. injection of histamine in the anaesthetized dog but is inactive on the effects of acetylcholine and prostaglandin E1. Other sulfhydryl agents (alpha-thioglycerol, 2-mercaptoethanol, 2,3-dimercapto-l-propanol, DL-cysteine, glutathione, diethyldithiocarbamate) can similarly modify the effects of histamine on blood pressure but two metal complexing agents (CaNa2 EDTA and orthophenantroline) are inactive. After pretreatment with indomethacin (10 mg/kg) or cimetidine (0.5 mg/kg/min) D-penicillamine still increases the effect of histamine but not after pretreatment with pyrilamine maleate (1 mg/kg). Moreover D-penicillamine does not modify the blood pressure drop due to dimaprit but increases that to 2-(2-pyridyl) ethylamine. It is concluded that D-penicillamine and some other sulfhydryl agents can increase the blood pressure lowering effects of histamine at the level of vascular H1-receptors by a sensitizing mechanism which might involve the rupture of a disulfide bridge.


Penile erection induced by apomorphine and N-n-propyl-norapomorphine in rats. The intraperitoneal injection of apomorphine (APO) or N-n-propyl-norapomorphine (NPA) to adult male rats markedly increases the incidence of episodes of penile erection (PE). The effect is dose related for a dose range of APO from 25 to 500 microgram kg-1 and NPA from 1.25 to 50 microgram kg-1. Higher doses are progressively less effective until 1 and 5 mg kg-1 of APO and NPA, respectively, suppress even the natural occurrence of PE. APO differs from NPA not only on a potency basis but also in that doses of APO which elicit stereotypy no longer evoke PE, while a wide range of doses of NPA (12.5 to 500 microgram kg-1) produces simultaneously strong PE activation and stereotypy. The sexual stimulant response to APO and NPA is prevented by haloperidol (0.3 mg kg-1) and sulpiride (50 mg kg-1) but is not affected by domperidone (3 mg kg-1), an inhibitor of extracerebral dopamine receptors.


Microbial oxidation of methane and methanol: purification and properties of a heme-containing aldehyde dehydrogenase from Methylomonas methylovora. Procedures for the purification of an aldehyde dehydrogenase from extracts of the obligate methylotroph, Methylomonas methylovora are described. The purified enzyme is homogeneous as judged from polyacrylamide gel electrophoresis. In the presence of an artificial electron acceptor (phenazine methosulfate), the purified enzyme catalyzes the oxidation of straight chain aldehydes (C1--C10 tested), aromatic aldehydes (benzaldehyde, salicylaldehyde), glyoxylate, and glyceraldehyde. Biological electron acceptors such as NAD+, NADP+, FAD, FMN, pyridoxal phosphate, and cytochrome c cannot act as electron carriers. The activity of the enzyme is inhibited by sulfhydryl agents [p-chloromercuribenzoate, N-ethylmaleimide and 5,5-dithiobis (2-nitrobenzoic acid)], cuprous chloride, and ferrour nitrate. The molecular weight of the enzyme as estimated by gel filtration is approximately 45000 and the subunit size determined by sodium dodecyl sulfate-gel electrophoresis is approximately 23000.  The purified enzyme is light brown and has an absorption peak at 410 nm. Reduction of enzyme with sodium dithionite or aldehyde substrate resulted in the appearance of peaks at 523 nm and 552nm. These results suggest that the enzyme is a hemoprotein. There was no evidence that flavins were present as prosthetic group. The amino acid composition of the enzyme is also presented.


Juxtaposition of somatostatin cell and parietal cell in the dog stomach. Immunohistochemical and silver impregnation techniques were applied to demonstrate the somatostatin producing D cells in the dog gastric body (oxyntic area). It was revealed that the D cells were frequently in direct contact with parietal cells, either by their cell body invaginated into or crescently attached to a parietal cell or by extending a cytoplasmic process ending in a synaptic button-like swelling. Some D cells and their processes appeared to contact chief cells. This morphological finding is correlated to the hypothesis that the D cells might receive an unknown stimulus, possible a mechanical extension of the gastric wall, and by its secretion, somatostatin, inhibit the release of gastric acid and enzymes. The direct juxtaposition and synapse-like connection of D and parietal cells seem to symbolize the continuity of neurons and endocrine cells (paraneurons) as well as neurotransmitters and hormones.


[Therapy of extrapyramidal motor disturbances by tiaprid (author's transl)]. In animal experiments Costall and Naylor (1977) showed that Tiaprid, a benzamide derivative of the orthopamids, inhibits dopamine receptors in the caudate nucleus and putamen but not in the mesolimbic system. Involuntary movements in patients with extrapyramidal movement disorders were reduced by 300 mg daily. Good results were obtained in 56% of 93 patients (25 in this study and 68 from the literature). On the whole the efficacy of Tiaprid seems far better than that of neuroleptics, and side effects are definitely fewer.


Structural elements in adenovirus cores. Evidence for a "core shell" and linear structures in "relaxed" cores. "Freeze-fracture negative staining" of adenovirus type 5 revealed the virus cores as internal bodies with a fine granular surface which at high magnification shows reticular and ring-like patterns. This indicates that the virus protein V forms a thin surface layer for which a name "core shell" is proposed. Virus cores prepared by heating virus particles in sodium deoxycholate (DOC) relaxed into curved filaments or several rods by means of EGTA and high salt, respectively. High pH treatment had similar effects as high salt. Rod-like elements were also observed in ultrathin sections of the "DOC-cores". Fresh cores exhibited circular dichroism (C.D.) with similar features as described for nucleosomes (COWMAN and FASMAN, ref. 5). This indicates that the DNA has an orderly arrangement in the cores. EGTA had no  effect on C.D. spectra but high salt treatment abolished the positive peak in 10 minutes. It is concluded that the adenovirus nucleocapsid is a linear structure, presumably a 120-150 Angstrom thick filament folded 5 to 6 times into "rods" as previously observed by freeze-fracturing.


Bunyavirus development in arctic and Aedes aegypti mosquitoes as revealed by glucose oxidase staining and immunofluorescence. Northway virus replication has been detected in salivary glands of wild-caught Culiseta inornata and Aedes communis mosquitoes from the western Canadian Arctic after incubation at 4 degrees C for 9 to 11 months, and after incubation at 13 degrees C for 3 to 4 months after they received virus by oral ingestion or intrathoracic injection. Aedes hexodontus supported Northway virus replication after incubation at 13 degrees C for one month after intrathoracic injection. Aedes aegypti supported Northway virus replication after incubation at 13 degrees C or 23 degrees C for 6 to 28 days following intrathoracic injection. A larval isolate of California encephalitis virus (snowshoe hare subtype) multiplied in all 3 species of arctic mosquito after incubation at 13 degrees C for 1 to 3 months after virus was administered by oral ingestion or intrathoracic injection. Virus was detected in salivary glands of Cs. inornata after 329 days incubation at 4 degrees C after intrathoracic injection. Bunyavirus antigens in salivary glands of arctic and domestic mosquitoes were detected by the glucose oxidase immunoenzyme technique somewhat less frequently than by assay for virus infectivity.


Vascular effects of etilefrine. Further studies to substantiate the predominant indirect sympathomimetic action of this agent. The suggested use of etilefrine in the treatment of patients with orthostatic hypotension is based on the premise that it has an action similar to that of noradrenaline (Miller, Wiener and Bloomfield, 1973). However, earlier work from this laboratory (Frost, Frewin and Gerke, 1977; Frost, Frewin, Gerke and Downey, 1978; Frost, Halloran, Frewin, Gerke and Downey, 1978) on blood vessels in the rat tail has suggested that the drug acts predominantly as an indirect sympathomimetic agent. The present study examined the action of etilefrine on the central artery of the rabbit ear. This vessel is known to have a rich sympathetic innervation (de la Lande, Frewin and Waterson, 1967) and has the added advantage that it can be surgically denervated. It therefore became possible to examine the effects of etilefrine on both normal and denervated arteries and to quantitate the extent to which the drug relied on the symphathetic nerves for its vasoconstrictor effects.


Nicafenine, a new analgesic. I. Synthesis and physicochemical properties. The synthesis of 2-[(7-chloro-4-quinolyl)-amino] benzoic acid 3-pyridine carboxamide-N-ethyl ester (nicafenine) was carried out by a new method using isatoic anhydride. The IR, NMR, MS and UV spectrophotometric studies are described, together with the characteristics of this compound.


Interaction of DL-, D- and L-propranolol with the transport system of glucose in human erythrocytes. The effect of D-, L- and DL-propranolol on the glucose uptake in human erythrocytes was studied. It was observed that all three compounds competitively inhibit the glucose transport and have identical inhibition constants. The pH dependence of the inhibition constant indicates that uncharged propranolol is a more potent inhibitor than the charged one. The thermodynamic parameters of the interaction of propranolol with the glucose transport system were determined and discussed.


[Studies on lytic enzyme activities of bacteria and streptomycetes against Candida guilliermondii after partial purification with ammonium sulfate from shaking- and fermentation cultures (author's transl)]. Two bacteria and two streptomycetes strains, capable to degrade cell walls of Candida guilliermondii, were isolated from soils. Growth and enzyme production of these strains were investigated on synthetic and complex media in shaking culture and under fermentation conditions. The isolated microorganisms possessed lytic enzyme activities against living and autoclaved yeast cells. The lytic enzyme complex of the culture medium of microorganisms was partially purified by ammonium sulfate precipitation. After this purification step the lytic enzyme activity of the bacteria was higher that of the streptomycetes towards the control. The lytic enzyme activity of the bacteria was thermostable (30 min, 80 degrees C), that of streptomycetes thermolable (inactive - greater than 40 degrees C). The pH-optimum of the bacteria enzymes was in the range of 5.0-7.5, that of the streptomycetes 5.0-8.5.


Thermostable aminopeptidase from local isolate of Bacillus stearothermophilus. Two of 63 isolates from different sources were very active in producing thermostable aminopeptidase. Comparing the two isolates, RR-2247 gave the highest enzyme activity and was identified as Bacillus stearothermophilus. The enzyme was isolated from the cells by a sonic vibration for 3 minutes at 20 KC/S. The enzyme shows optimum activity over the pH range of 7.5-8.0 at 65 degrees C. The apparent temperature optimum was about 70 degrees C. Addition of 0.0001 M Co2+ ions stabilized the enzyme in solution for 60 minutes at 80 degrees C. The heat of the reaction (delta E) was calculated to be +10,600 cal/mole. The standard entropy change (delta S) and the standard free energy change (delta G) were + 22.9 cal/mole/degree and -341 cal/mole at 50 degrees C. Amino acids composition and infra-red spectrum of the enzyme were also studied.


Effect of Clostridium perfringens neuraminidase on viability and antigenicity of human leukemic myeloblasts. The effect of increasing concentrations of Cl. Perfringens neuraminidase and of pH on the dye exclusion ability and lymphocyte stimulating capacity of leukemic myeloblasts was studied. The higher the neuraminidase concentration, or the lower the pH was, the more myeloblasts died and the less the myeloblasts stimulated lymphocytes. Myeloblasts treated at a neutral pH and at low enzyme concentrations retained, but did not increase their antigenicity.


Variations in the virulence of Plasmodium gallinaceum for avian embryos after repeated passages in mosquitos and chickens. Inoculation of 1 x 10(6) parasites of Plasmodium gallinaceum from chicks infected with sporozoites into 10-day chicken embryos produced infections with wide ranges of peak parasitaemia. It is thought that these variations reflect alterations in the genetic moiety of the parasites after recombinations occurring during the sexual cycle in different batches of mosquitos.


Effects of work and acute beta-receptor blockade on myocardial noradrenaline release in congestive cardiomyopathy. Systemic hemodynamic changes and noradrenaline concentrations in coronary sinus blood were studied at rest and during work before and after acute beta-receptor blockade. Patients with congestive cardiomyopathy were compared to patients with primary valvular diseases and to healthy subjects. Noradrenaline concentrations were higher in coronary sinus blood than in arterial blood and increased after beta blockade and during work. Noradrenaline concentrations were more increased in patients with more pronounced myocardial failure and did not seem to separate patients with congestive cardiomyopathy from those with valvular disease. Patients with congestive cardiomyopathy showed a good hemodynamic tolerance toward acute beta blockade.


Effect of cholesterol-rich diet on the content of nicotinamide nucleotides, adenine nucleotides and acetyl-CoA in the liver, the vascular wall and the kidney of spontaneously hypertensive rats (SHR). The liver content of NAD and of adenylic nucleotides of normally fed spontaneously hypertensive rats (SHR) is lower than in normotensive rats. The cholesterol-rich diet does not change the liver NAD level. However it decreases adenine nucleotides and increases the level of acetyl-CoA and of NADP. Normal refeeding after a long-term cholesterol-rich diet induces an increase in the low levels of the coenzymes (moth NAD and adenine nucleotides). The liver coenzyme changes caused by the cholesterol-rich diet and by the normal refeeding of SHR are opposite to those established in normotensive rats. Vascular wall nicotinamide coenzymes in SHR are lower than in ulistar rats. The vascular wall of SHR reacts to the cholesterol-rich diet by a rise in NAD, i.e. conversely to the reaction observed in the liver of SHR and vascular wall of normotensive rats. Normal refeeding induces a further increase in the content of coenzymes. These results show that the effect of cholesterol-rich diet on the coenzyme content in the SHR is opposite to that in normotensive rats. The renal redox-system NAD+-NAD-H is more sensitive to the cholesterol-rich diet than the liver one, and its coenzyme changes indicate a greater reduction state, a reaction pattern which is typical for renal hypoxia. The results suggest that the cholesterol-rich diet influences the metabolism of the liver, the kidney and the vascular wall in a different way and to a different degree. SHR have a specific type of reaction to this cholesterol-rich diet.


Bone marrow transplantation in acute leukemia: current status and future directions. Bone marrow transplantation is an experimental approach to the treatment of patients with acute leukemia, aplastic anemia, and other neoplastic and genetic diseases. To date, long-term disease-free survival has been achieved in a small proportion of carefully selected patients with resistant acute leukemia. While results are not optimal, they are acceptable in late stage patients where there are no effective alterates. Major problems in marrow transplantation for leukemia include tumor resistance and a spectrum of immunologic complications including GVHD, immunodeficiency, and interstitial pneumonitis. Potential approaches to these problems have been suggested. Progress in any one area would have a substantial impact on improving survival and extending the applicability of marrow transplantation to patients at an earlier stage of their disease.


Effect of parasympathetic and beta-adrenergic blockade on the umbilical circulation in the unanesthetized fetal sheep. Parasympathetic and beta-adrenergic blocking agents were administered to near term chronically instrumented sheep. Parasympathetic blockade resulted in a significant increase in fetal heart rate and fetal arterial blood pressure, with a minimal nonsignificant increase in umbilical blood flow. beta-Adrenergic blockade resulted in a decrease in fetal heart rate and umbilical blood flow, though neither was statistically significant. There was no change in arterial blood pressure. The net result of parasympathetic and beta-adrenergic blockade on fetal heart rate suggests that the intrinsic rate is the same as when these influences are present.


[Comparative study on the depressive action of several benzodiazepine minor tranquilizers (author's transl)]. The potencies of four benzodiazepine minor tranquilizers in depressing respiratory function were investigated in rats and cats anesthetized with pentobarbital. The effect of the drug on respiration was studied in the rat, and the effect on the phrenic nerve activity which reflects the activity of an inspiratory centre was investigated in the cat vagotomized bilaterally at the level of the neck. The change of blood pressure, heart rate and pCO2 in expiration were also recorded simultaneously in experiments with the cat, an infra-red CO2 gas analyzer (Model LB-1, Beckman) was used to measure the pCO2. Respiration in the rat was decreased by the oral administration of diazepam 10, 20 mg/kg or chloridazepoxide 20, 40 mg/kg. Although the pre-administration level of ventilation was not decreased by oxazolam or chloxazolam, both 20, 40 mg/kg, p.o., the level after administration was slightly lower than that after the administration of CMC alone. Diazepam, given intravenously either as a CMC-suspension or as the preparation Cercine, in the dose of 0.5 mg/kg, suppressed both the number of the burst discharges and the magnitude of the integrated signal of the discharge of the phrenic nerve of the cat. Chlordiazepoxide 1 mg/kg, i.v. also slightly decreased the magnitude of the integrated signal. Oxazolam 1 mg/kg, i.v. had little effect on the phrenic activity. Cloxazolam 1 mg/kg, i.v., on the other hand, tended to increase the magnitude of the integrated signal but only immediately after the administration. It is suggested that the potencies which depress the respiratory function vary for each minor tranquilizer, namely the ddpressive actions of oxazolan and cloxazolam are weaker than those of diazepam and chloridiazepoxide.


[Effects of betamethasone 17, 21-dipropionate on activities of glycogen synthase and tyrosine aminotransferase in fetal rat liver in organ culture (author's transl)]. Betamethasone 17, 21-dipropionate (BDP) does not have glycogenic activity and antagonizes cortisol in glycogenesis in fetal rat liver explants. In an attempt to elucidate whether BDP commonly has an antagonistic effect on the glucocorticoid responsive system in fetal rat liver, effects on activities of glycogen synthase and tyrosine aminotransferase were examined. Cortisol increased both total and a activities of glycogen synthase at concentrations above 3 x 10(-8)M. BDP, unlike cortisol, did not increase total synthase activity at 10(-6)M and antagonized cortisol (10(-6)M), but like cortisol, it did increase synthase a activity. Both cortisol and BDP increased tyrosine aminotransferase activity at concentrations above 10(-8)M, BDP did not always act as an antagonist in the glucocorticoid responsive systems in fetal rat liver.


Comparison of sputum counterimmunoelectrophoresis and culture in diagnosis of pneumococcal pneumonia. The diagnostic value of counterimmunoelectrophoresis performed on sputum was compared with that of sputum culture. The detection of pneumococcal polysaccharide in sputum showed a better correlation with the presence of pneumococcal pneumonia than the recovery of pneumococci by culture. The authors conclude that sputum counterimmunoelectrophoresis can provide diagnostic guidance to physicians awaiting the results of sputum culture and aid in the interpretation of cultural findings.


Regulation of melanin production by Cryptococcus neoformans. Species of Filobasidiella, the agents of cryptococcosis, produced melanin-like pigments within 4 to 48 h with diphenol, aminophenol, and diaminobenzene compounds as substrates. The rate of phenyloxidase activity was found to be regulated by glucose and nitrogen catabolite repression. Increased glucose concentration reduced pigmentation of all serotypes of Filobasidiella, whereas repression by nitrogen sources varied with the strain. Glutamine repressed the phenyloxidases of all isolates except those of serotype B, and (NH4)2SO4 repressed the phenyloxidase of all isolates except that of serotype A. Tyrosine and glycine appeared to be near optimal for phenyloxidase activity but not necessarily for growth of all strain examined. Representatives of serotype C were unique in that their phenyloxidase system was adpative in contrast to the constitutive system found in the other serotypes. No single medium was found to support pigmentation of all strains of Cryptococcus neoformans within a 72-h incubation period; false-negative reactions can occur.


Cellular and environmental variables determining numbers of flagella in temperature-shocked Naegleria. Naegleria gruberi amebae normally transform into biflagellated cells. When subjected to high temperatures during flagellate differentiation, populations develop an average of 4-5 flagella/flagellate. Attempts to maximize this phenomenon by altering cellular and environmental variables revealed that: (a) few Naegleria isolates become multiflagellated: strain NB-1 gives the greatest response to heat shocks; (b) temperature is the most critical variable: highest numbers of flagella are obtained only if cells are temperature-shocked at precisely 38.2 +/- 0.1 C, then returned to 19-22 C to complete differentiation; (c) although pH alone does not affect numbers of flagella, a pH optimum of 5.5-7.0 exists for temperature-shocked cells; and (d) single cells in microdrops become multiflagellated, but the population response is density-dependent. Optimal conditions are described for growing, washing, and transforming amebae to generate reproducibly highest numbers of flagella.


Evidence for NADH- and NADPH-linked glutamate dehydrogenases in Trypanosoma cruzi epimastigotes. Two glutamate dehydrogenases, NADH-linked (EC 1.2.1.2) and NADPH-linked (EC 1.2.1.4) were isolated from the epimastigote forms of Trypanosoma cruzi and purified. Both enzymes exist as hexamers. The molecular weights of the native NADH-and NADPH-linked glutamate dehydrogenases were estimated to be 360,000 and 265,000, respectively, and those of the subunits to be 58,000 and 43,000, respectively. The isoelectric point of the NADH-linked dehydrogenase is at pH 5.25 and that of the NADPH-linked enzyme at pH 5.1. The activities of both enzymes are regulated by product inhibition. In addition, purine nucleotides were shown to be potent inhibitors of the NADH-linked glutamate dehydrogenase.


Comparative studies on dihydrofolate reductases from Plasmodium falciparum and Aotus trivirgatus. Dihydrofolate reductase (E.C. 1.5.1.3) from Plasmodium falciparum and from its host, the owl monkey (Aotus trivirgatus), were partially purified and characterized. The molecular weight of the parasite enzyme was estimated to be over 10 times as high as that of the host enzyme. The host enzyme had 2 pH optima whereas the parasite enzyme only one. The activity of the host enzyme was greatly stimulated by KCl and urea, while that of the parasite enzyme was inhibited at high concentrations of such chaotropic agents. Km of the parasite enzyme was significantly higher than that of the host enzyme. The parasite enzyme had much lower Ki for pyrimethamine than the host enzyme. Dihydrofolate reductases isolated from pyrimethamine-resistant and pyrimethamine sensitive strains of P. falciparum were found to be similar.


Effect of phospholipase A2 on purified gastric vesicles. The phospholipid and fatty acid composition and role of phospholipids in enzyme and transport function of gastric (H+ + K+)-ATPase vesicles was studied using phospholipase A2 (bee venom). The composition (%) was phosphatidyl-choline (PC) 33%; sphingomyelin (sph) 25%; phosphatidylethanolamine (PE) 22%; phosphatidylserine (PS) 11%; and phosphatidylinositol (PI) 8%. The fatty acid composition showed a high degree of unsaturation. In both fresh and lyophilized preparations, even with prolonged incubation, only 50% of phospholipids were hydrolyzed, but the amount of PE and PS disappearing was increased following lyophilization. There was a marked decrease in K+-ATPase activity (75%) but essentially no loss of the associated K+ p-nitrophenyl phosphatase was found. ATPase activity could be largely restored by various phospholipids (PE greater than PC greater than PS). There was also an increase in Mg2+-ATPase activity, partially reversed in fresh preparations by the addition of phospholipids (PE greater than PS greater than PC). Proton transport activity of the preparation was rapidly inhibited, initially due to a large increase in the HCl permeability of the preparation. Associated with these enzymatic and functional changes, the ATP-induced conformational changes, as indicated by circular dichroism spectra were inhibited.


Alkaline phosphatase of basal lateral and brush border plasma membranes from intestinal epithelium. The alkaline phosphatase present on isolated brush border and basal lateral membranes of rat duodenal epithelium were examined by means of a variety of biochemical assays and physical methods. The two alkaline phosphatases have similar pH optima of 9.6--9.8, similar substrate km's for p-nitrophenyl phosphate (PNPP) of 71 micromolar, similar responses to the inhibitors 2-mercaptoethanol, theophylline, phenylalanine, and ethylenediaminetetraacetic acid (EDTA), similar sensitivities to calcium, magnesium, zinc, sodium, and potassium, and similar insensitivities to digestion with trypsin of papain. The two enzymes also exhibit similar molecular weights on SDS-polyacrylamide gels in the range 124,000--150,000, and both enzymes show an Rf value of 0.092 on Triton X-100 polyacrylamide gels, indicating similar intrinsic charges. The Vmax of the brush border enzyme is ten times greater than that of the basal lateral enzyme, 140 mumoles/mg-h as opposed to 14 mumoles/mg-h. The differences in Vmax are a reflection of the known distribution of alkaline phosphatase in rat duodenum, there being more alkaline phosphatase activity present on the brush border than on the basal lateral surface. One other major difference was observed between the two enzymes, the stimulation of the basal lateral and not the brush border alkaline phosphatase by SDS, Triton X-100, or cholate. We conclude that the enzymes are very similar to one another and probably perform similar membrane functions.


Regional distribution of membrane-bound gamma-glutamyl transpeptidase activity in mouse brain. Comparison with rabbit brain. Activity of membrane-bound gamma-glutamyl transpeptidase (gamma-GTP) was examined in various regions of mouse brain, in capillaries of the cerebral cortex and in telencephalic choroid plexuses. The level of activity in the capillaries was double and that of the choroid plexus nine times that of the gamma-GTP activity found in the brain, septum, hippocampus, hypothalamus, thalamus, cerebellum, frontal cortex, pons, medulla oblongata, and amygdala. Histochemically the gamma-GTP activity was demonstrated in the surface membranes of choroidal cells and in the endothelium of small capillaries. The activities of gamma-GTP of cerebral cortex, choroid plexus, and capillaries from rabbit were 5--17 times greater than those from corresponding areas of mouse brain. While 30 mM methionine stimulated (in vitro) the enzyme from mouse brain, no such effect was observed with the enzyme activity from rabbit brain. The gamma-GTP activity from the capillaries of cerebral cortex of both mouse and rabbit was not affected by the presence of methionine. These findings suggest existence of differences in the specificity of gamma-GTP activity in these two species.


Seizure proneness and neurotransmitter uptake. The ability of midbrain homogenates from two strains of mice to accumulate several putative neurotransmitters, or their precursor in the case of acetylcholine, has been examined. The high-affinity transport mechanisms toward glutamate, GABA, dopamine, and glycine were similar in both strains. The seizure-prone DBA21BG strain had a significantly higher capacity to transport choline than did the relatively seizure-resistant C57BL/6 IBC mice. Howaver, no difference in the density of muscarinic binding sites in the two mouse strains was found.


Disaggregation of brain polysomes after LSD in vivo. Involvement of LSD-induced hyperthermia. LSD-induced hyperthermia is implicated in the brain-specific disaggregation of polysomes which is induced following intravenous administration of the drug to rabbits. Both LSD-induced hyperthermia and brain polysome disaggregation were found to increase in parallel under conditions which accentuated the effect of the drug on brain protein synthesis. Pretreatment with neurotransmitter receptor blockers or placing the animal at an ambient temperature of 4 degrees C after LSD administration prevented both hyperthermia and brain polysome disaggregation. The administration of apomorphine, which causes hyperthermia in rabbits also caused disaggregation of brain polysomes. Direct elevation of the body temperature to levels similar to that found after LSD was achieved by placing animals at an ambient temperature of 37 degrees C. Under these conditions a brain-specific disaggregation of polysomes resulted which was not due to RNAase activation. After either LSD or direct heating, the brain polysome shift was associated with a relocalization of polyadenylated mRNA from polysomes to monosomes as determined by [3H]polyuridylate hybridization. Since polysome disaggregation was found only in brain, it appears that the brain may be more sensitive to elevations in body temperature compared to other organs.


Purification and covalent coupling of calf brain prolidase. We have investigated methods of stabilizing prolidase by chemical modification and covalent coupling to various supports, for use in protein hydrolysis and possible use in enzyme replacement therapy. Purified acetone powder of calf brain prolidase was further purified by gel filtration on Sephadex G-200 and chromatography on DEAE-Sephadex A25. Polyacrylamide gel electrophoresis showed that the number of bands was reduced from 11 to 2. Since yields were low, the purified (NH4)2SO4 fraction was used in all experiments. Thiolation of the enzyme reduced the amount of protein coupled to AH- or CH-Sepharose 4B. Activities were highest when the protein was linked through its carboxyl groups. The coupled enzyme showed much greater thermal stability than its free counterpart. Of the bound preparations, the thiolated was less stable than the untreated. Untreated and thiolated enzymes bound to either matrix showed higher activity at low pH and less at high pH than the free material. Thiolation shifted the pH maximum from 6.8 to 7.5. The free thiolated enzyme and that bound to activated SH-Sepharose 4B showed greater thermal stability and a broader pH range of optimal activity than the bound untreated enzyme. These results show that prolidase can be immobilized by coupling to an insoluble matrix through various types of covalent bonds with retention of activity and increased stability.


Pyridoxal 5'-phosphate levels in brain after treatments which impair cerebral glucose metabolism. Pyridoxal 5'-phosphate (PLP) concentrations were measured in brains of rats to determine whether a deficiency of this coenzyme was a common feature in hepatic coma, ethanol intoxication, and in animals treated with L-dopa or with 5-hydroxytryptophan (5-HTP) alone or with inhibitors of MAO or of L-aromatic amino acid decarboxylase. These treatments have been shown previously to be associated with reduced conversion of glucose to amino acids in brain. Cerebral PLP concentrations were reduced after some of these treatments, notably injection of ethanol, or L-dopa alone or with beta-phenylisopropylhydrazine, an inhibitor of MAO, or of 5-HTP together with N-[beta-(chlorophenoxy)ethyl]cyclopropylamine hydrochloride, Lilly 51641, another MAO inhibitor. However, in other circumstances where inhibition of conversion of glucose to amino acids has been shown (treatment with 5-HTP, or with Lilly 51641 or with [N-(D,L-seryl)-N'-2,3,4-trihydroxybenzyl]hydrazine, an inhibitor of L-aromatic amino acid decarboxylase, together with L-dopa or with 5-HTP), PLP levels in brain were unchanged, or were increased (in hepatectomized rats).


The evaluation of tiodonium chloride as an antiplaque and anticaries agent. V. Effects on plaque microbiology and plaque and saliva pH. The purpose of this study was to determine the effect of a tiodonium chloride mouthrinse on the microbial composition of plaque and the acidogenic properties of plaque and saliva after challenge with sucrose solutions. Fifty-five participants were grouped on the basis of their tendency to form plaque, then randomly assigned to use either a placebo or a 0.3% tiodonium chloride rinse. After a prophylaxis all oral hygiene was suspended, supervised rinsings were conducted twice daily for four days and once on day 5. One-half hour after the last rinse, plaque was removed from the right mandibular second molar for microbiological evaluation. Plaque was also removed from the right quadrants and mixed with 10% sucrose. The pH of the mixture was measured immediately and after 15 minutes. Saliva was collected before and 30 minutes after the final rinse and mixed with 5% glucose. pH was determined initially and after five hours. Tiodonium chloride rinses significantly reduced the viable organisms in plaque. It also restricted the ability of plaque or saliva to metabolize sucrose as monitored by pH changes. The results suggest that tiodonium chloride might decrease dental caries because of its inhibiting effect on plaque microflora and acid production by plaque and saliva.


Widely disseminated cutaneous candidosis in adults. Of 9 adults, 5 males, 4 females, with wide dissemination of Candida albicans skin lesions, the eruption started in the groin, from which it spread to other areas in most cases. In 5 cases the disseminated lesions were papulo-pustular; the rest were erythematous-squamous. Hyphae and yeast cells of C. albicans were found on direct microscopy. Diabetes was present in 5 patients, lymphoma in 1, and bullous pemphigoid in another. Onychia and paronychia were found in 7 patients, intertriginous lesions of the fingers in 4 and oral thrush in 2. Intradermal skin tests were negative. The percentage and absolute numbers of T-lymphocytes were normal in 6 of 7 patients, whereas their functional activity was imparied in 4 of 6 patients, as evidenced by the negative Graft-versus host reaction. The role of concurrent disease in the pathogenesis of the candidosis is discussed.


Orchiopexy using microvascular surgical technique. Orchiopexy of high intra-abdominal testes with division of the internal spermatic artery and vein is associated with subsequent testicular atrophy in a significant percentage of cases. We herein describe 2 patients in whom arterial supply and venous drainage to the testis were maintained using microvascular anastomosis. The internal spermatic artery and vein were anastomosed to the deep inferior epigastric artery and vein. Patency of the vascular anastomosis was verified by subsequent radionuclide examinations and selective arteriography in 1 patient.


[Changes in the ruminal contents in suppurative surgical infection in cattle]. Rumen content (pH, number of infusoria, quantity of volatile fatty acids and ammonia) was studied in 151 cattle (50 healthy animals, 15 with experimental suppurative infection and 86 with spontaneous suppurative infection). In cases of cattle suppurative infection a statistically significant reduction was observed in the four rumen content indices: pH from 7.61 +/- 0.02 fell to 6.90 +/- 0.06; number of infusoria--from 295 820 +/- 2890 per cm3 fell to 75 867 +/- 1260 per cm3; volatile fatty acids from 919.7 +/- 10.08 mg% diminished to 489.48 +/- 18.91, and ammonia from 27.69 +/- 0.51 mg% was reduced to 12.23 +/- 0.73 mg%. In case of recovery a tendency toward normalizing rumen content was observed.


Ultracytochemical characterization of non-specific acid phosphatase activities in Saccharomyces cerevisiae. Glutaraldehyde prefixation causes a considerable inactivation of the acid phosphatase of yeast protoplasts in dependence on the duration of aldehyde influence. Lead ions necessary for ultracytochemical demonstration effect a still stronger inhibition of enzymatic activity. Prefixation, however, protects the enzyme from further inhibition by lead. At pH 4.4 in intact cells acid phosphatase activities are mainly localized in the periplasmic space and in vesicles fused with the plasma membrane. The cell wall and cytoplasm usually remain free of reaction products. On the cell surface activities are found in form of globular lead deposits. At pH 5.2 and 6.3 the periplasmic activity appears decreased compared to that at lower pH values and the intracellular activity is increased. The plasma membrane of protoplasts is completely free of precipitates. The intracellular activity sites of protoplasts (cisternae of endoplasmic reticulum and/or Golgi-like system, small vesicles, central vacuole, nuclear envelope) are the same as for intact cells. The occurrence of at least two forms of acid phosphatase in S. cerevisiae id deduced.


[Oxidative degradation of dibenzylsulfide]. Dibenzylsulfid (DBS) as a model of the organic sulfur compounds in crude oil was converted by a mixed culture (containing Pseudomonas aeruginosa) into several water soluble organic substances. Whereas these compounds are detectable with DC- and IR-spectroscopic techniques, benzylmercaptoacetic acid (BMA) was the only isolated product of DBS utilization. Efficiency of degradation, respectively, accumulation of BMA were dependent on aeration and pH-regulation.


Inhibition of photosynthetic electron transport in tobacco chloroplasts and thylakoids of the blue green alga Oscillatoria chalybea by an antiserum to synthetic zeaxanthin. An antiserum to synthetic Zeaxanthin inhibits photosynthetic electron transport on the oxygen-evolving side of photosystem II in tobacco chloroplasts and thylakoids of the filamentous blue-green alga Oscillatoria chalybea. The inhibition site lies for both species between the site of electron donation of water or tetramethyl benzidine and that of diphenyl carbazide or manganese II ions. Typical photosystem I reactions are not impaired by the antiserum. The effect of the antiserum concerning the inhibition site is practically identical to that of the earlier described antiserum to violaxanthin. However, the degree of inhibition seems to be generally somewhat lower with the antiserum to Zeaxanthin, than with that to violaxanthin which hints at a lesser accessibility of zeaxanthin, in the tylakoid membrane in comparison to violaxanthin. In the course of these investigations new evidence was obtained that the oxygen-evolving side of the electron transport scheme is differently organized in Oscillatoria chalybea when compared to tobacco chloroplasts. Thus, the silicomolybdate reduction with water as the electron donor is sensitive to DCMU in these algae.


[The influence of cytochalasin B, colchicine, and vinblastine on the attachment of Entamoeba histolytica to glass surfaces (author's transl)]. The attachment of E. histolytica trophozoites from monoxenic TPS-medium to glass surfaces was studied at different temperatures and pH values and in the presence of cytochalasin B, colchicine, and vinblastine. At pH 7.0 and at 36 degrees C optimal adhesion rates of the amebae were observed in the range from 80% to 95%. Marked inhibition of adhesion was noted at higher concentrations of cytochalasin B. The adhesion rate was reduced to 50% by 50 micrograms/ml CB. Higher dosages successively prevented nearly all adhesion. Colchicine was without any effect. Vinblastine had a certain low effect but only at very high dosage. The observations are consistent with the assumption that the adhesion process is at least partially mediated by cytochalasin-sensitive contractile microfilaments, whereas microtubuli are obviously not involved in the cell-substrate adhesion.


A comparison of the non-specific acid phosphomonoesterase activity in the larva of Phocanema decipiens (Nematoda) with that of the muscle of its host the codfish (Gadus morhua). The non-specific phosphomonoesterase (enzyme I) extracted from the larva of the codworm (Phocanema decipiens) is different from the enzyme (enzyme II) from the muscle of its host, the codfish (Gadus morhua). The pH optima were 4.0 and 4.5, and the KM values for p-nitrophenyl phosphate hydrolysis were 1.8 mM and 6.5 mM for enzymes I and II respectively. The specific specific activity in units (0.01 mumol/min) per mg protein was 4.80 +/- 0.85 and 0.54 +/- 0.07 for enzymes I and  II respectively. The specific activity from uninfected muscles was only 0.39 (SD +/- 0.017) units per mg of protein. Both enzymes were inhibited by NaF, HgCl2, and cysteine but were stimulated by 2-mercaptoethanol. EDTA and iodoacetamide had no effect on enzyme I but enzyme II was activated by EDTA and inhibited by iodoacetamide. Cadmium ions inhibited both the enzymes but a conspicuous feature with enzyme II was in the increase in percentage inhibition by lowering the concentration of CD2+.


Identity and lipase productivity of a mesophilic actinomycete isolated from Egyptian soil. 1. A mesophilic lipolytic actinomycete was isolated from Egyptian soil and was identified as a strain of Streptomyces flavogriseus. 2. Lipase(s) produced by S. flavogriseus is (at least partly) constitutive in its (their) nature and can be produced in the absence of lipids, however, its production is stimulated in their presence. 3. S. flavogriseus was unable to grow at 40 degrees C or higher temperatures. However, lipase(s) produced at lower temperatures (e.g. 20, 25, 30 and 35 degrees C) were more active at 45 and 55 degrees C. This is probably due to the presence of a heat sensitive lipase inhibitor in the culture filtrate. 4. Optimum conditions for lipase(s) production by S. flavoriseus are pH 6.8, incubation for 48-72 hours at 35 degrees C with 0.8% castor oil as the carbon source in Dox liquid medium supplemented with 0.3% yeast extract. 5. Factors supporting good growth were not always the same as those stimulating lipase(s) production.


L-asparaginase-producing Streptomyces from the soil of Kuwait. Five actinomycete isolates (all belonged to the genus Streptomyces), capable of producing detectable amounts of L-asparaginase, were isolated from the soil of Kuwait after enrichment. The three most potent enzyme producers were identified as different strains of Streptomyces collinus. Factors affecting enzyme production by the strongest strain were examined. Synthetic media with asparagine as a nitrogen source stimulated more enzyme production than natural media. Starch and asparagine at final concentrations of 1 and 0.8%, respectively, were optimum for enzyme production. An initial pH of 8.5 for the growth medium and an incubation temperature of 28-30 degrees C in a static culture for 6 days stimulated enzyme production by the examined strain of Streptomyces collinus.


Activity of L-asparaginase in cells of Streptomyces karnatakensis. Eight isolates capable of producing varying quantities of L-asparaginase and all identified as members of the genus Streptomyces were isolated from the soil and a suitable technique for the assay of intracellular L-asparaginase in actinomycetes was developed. The most potent L-asparaginase producer was identified as a strain of Streptomyces karnatakensis. Static cultures of S. karnatakensis showed maximum enzyme activity with almost maximum growth while shaken cultures exhibited their activity after 48 hours of growth. This phenomenon is discussed in terms of possible feedback mechanism and/or the biosynthesis of certain pigments. L-asparaginase of S. karnatakensis proved to be mostly intracellular and the presence of L-asparagine in the culture medium though, stimulating yet not essential for the enyzme biosynthesis. Cells grown on L-asparagine showed amidase activity with other amides but at a reduced rate.


Inactivation of Pasteurella multocida within the mouse peritoneal cavity. Normal ICR mice were injected intraperitoneally with 0.5 ml of thioglycollate broth or 5 x 10(8) heat-killed Pasteurella multocida vaccine and the number of polymorphs, lymphocytes and macrophages in the peritoneal washout suspensions were determined at intervals up to 72 hours. The stimulated mice were challenged intraperitoneally with opsonized or unopsonized P. multocida at increasing time intervals and the rate of growth by the organisms in the washout suspension was determined up to 60 minutes later. The opsonized bacilli were taken up by the 6 hr. exudate cells (50-60% PMNs) and their growth inhibited more effectively than when the 72 hr exudate cells were tested (only 10% PMNs). When the challenge inoculum was introduced into the peritoneal cavities of mice stimulated 6 hrs previously with 5 x 10(8) heat-killed P. multocida vaccine, up to 80% of the bacilli were inactivated over a 30 minute period. However, when 72 or 250 hr peritoneal exudate cells were tested, the inoculum was not inactivated, but showed an increasingly lethal effect.


A proposed sero-grouping scheme for epidemiological investigation of food poisoning due to Clostridium perfringens type A. Serological studies with soluble and particulate antigens of Cl. perfringens type A revealed that enterotoxin and spore antigens could be used as a suitable marker for epidemiological studies. 94% of the food poisoning strains of Cl. perfringens type A could be grouped into 3 groups with the help of 2 enterotoxin-specific sera and 90% in 4 groups with antispore sera. Heat-sensitive strains were found to be antigenically more homogenous than the heat-resistant ones. Sera raised against spores of heat-resistant strains could not agglutinate spore of any of the heat-sensitive strains. Similarly no spores of heat-resistant strains were agglutinable by serum raised against spores of heat-sensitive strains. On the basis of typing efficiency the two antigen, viz enterotoxin and spore antigens were used in the serogrouping scheme proposed for the epidemiological investigation of food poisoning with Cl. perfringens type A. Used together, enterotoxin and spore agglutinogen form an antigenic formula for each strain showing the serogroup to which it belongs.


Production of hyaluronidase by propionibacteria from different origins. 114 strains of anaerobic and microaerophilic coryneform bacteria from different origins were investigated for production of free extracellular hyaluronidase (hyaluronate glycanohydrolase, EC 3.2.1.36). A quantitative technique was applied measuring the release of N-acetyl-glucosamine groups from purified human potassium hyaluronate. The strains belonged to the following species: Propionibacterium acnes, P. avidum, P. granulosum, P. lymphophilum, the formerly so-called Corynebacterium parvum, P. freudenreichii subsp. freudenreichii and shermanii, P. thoenii, P. acidi-propionici, C. minutissimum, and Arachnia propionica. All together, 59 out of 114 (approximately 51.8%) tested strains showed clearly measurable hyaluronidase activities. P. acnes, the propionibacterium species most frequently found in acne vulgaris lesions, proved to be the most active species tested, 44 out of 64 (approximately 68.8%) P. acnes strains being positive. 5 strains producing hyaluronate glycanohydrolase activities of more than 60 mU/ml in thioglycollate broth cultures could be detected. P. avidum and P. granulosum strains were positive in only 45.0% and 33.3%, respectively, and their mean hyaluronidase activities were significantly lower. Differences in hyaluronidase activities of P. acnes strains isolated from acne vulgaris lesions and strains from normal human skin could not be found. The possible pathogenic role of propionibacteria hyaluronidase in acne vulgaris is discussed.


Purine nucleoside triphosphates in Streptomyces hydrogenans. Influence of steroids on the relative nucleotide level. Various steroids in the culture medium of Streptomyces hydrogenans cause a rapid decrease of the relative GTP content of the cells. The relative ATP level is significantly diminished in the presence of progesterone and testosterone acetate. The initial decrease of the relative GTP content is proportional to the growth inhibitory effect of the steroids tested. There is no relationship between steroid-dependent induction of the synthesis of 20 beta- and 17 beta-hydroxysteroid dehydrogenase and the ability of the steroids to decrease the relative GTP content of the cells.


Autoimmune reactions associated with Mycoplasma pneumoniae infection. Patients with Mycoplasma pneumoniae infection often develop various autoantibodies including cold agglutinins, cold antibodies reacting with lymphocytes, antibodies against various tissue antigens, for instance brain and lung and smooth muscle antibodies. Various mechanisms that may be responsible for the induction of these autoimmune responses and the possible pathogenicity of these autoantibodies are discussed.


Pathogenicity of ureaplasmas for animals and man. Since their original isolation from the genital tract of man, ureaplasmas, previously termed T-strain mycoplasmas, have been isolated from a variety of animal species. Under experimental conditions they have been shown to cause mastitis in cattle, goats and mice, and observations made on naturally-occurring bovine pneumonia, as well as the results of experimental inoculation, suggest that ureaplasmas are responsible for a portion of bovine cuffing pneumonia. Ureaplasmas have been isolated from the genital tract of a wide variety of animals and have the potential for causing disease in this anatomical area, as the results of experimental intra-urethral inoculation of goats, for example, indicate. However, there are no data, as yet, to incriminate ureaplasmas as a cause of naturally-occurring genital tract disease nor as a cause of infertility, the latter being an area in which the results of studies are often conflicting and difficult to interpret. In man, the rôle of ureaplasmas in genito-urinary disease has been a bone of contention for many years. Experimentally, ureaplasmas produce bladder calculi in rats but so far there is no evidence that they do so in man. Further, there are no convincing data to support the notion that infertile couples possessing ureaplasmas should be treated with tetracyclines. There is an undoubted association between spontaneous abortion and low birth-weight on the one hand and the presence of ureaplasmas in the mother, abortus or infant on the other. However, evidence that the organisms cause abortion is lacking and whether they are directly responsible for low birth-weight is unknown. The association between chorioamnionitis and ureaplasma isolation is provocative enough to stimulate further work. In the case of non-gonococcal urethritis, the weight of evidence suggests that ureaplasmas cause the disease in some men. This is based on quantitative isolation, volunteer inoculation, as well as treatment studies including the use of antibiotics, such as rifampicin, which differentiate between chlamydiae and ureaplasmas.


Pathogenicity of the subspecies mycoides of Mycoplasma mycoides for cattle, sheep and goats. Recent work has shown that strains classified as M. mycoides subsp. mycoides may be separated into 2 types according to their growth rate and their behaviour in certain biochemical tests. The large colony (LC) types, most of which are from goats, are pathogenic for sheep and goats but apparently not for cattle. The small colony (SC) types include the classical contagious bovine pleuropneumonia (CBPP) strains from cattle and four strains from goats. These SC types are potentially pathogenic for cattle, sheep and goats. Strains of M. mycoides subsp. mycoides from CBPP differ in their virulence in cattle. The degree of virulence is correlated with the quantity of galactan produced in cultures of the organism, suggesting an important role for galactan in pathogenicity. This is consistent with the production by galactan of physiological effects in calves and in the enhancement of infection in cattle given galactan at the same time as cultures of the organism. Contagious caprine pleuropneumonia (CCPP) can be produced experimentally in goats using cultures of M. mycoides subsp. capri. Whether the glucan produced in such cultures is a factor in pathogenicity of this organism has not been determined. Hydrogen peroxide demonstrated in tracheal organ cultures of M. mycoides subsp. capri may contribute to its pathogenicity.


[The production of streptolysin O by beta-hemolytic streptococci of group A (author's transl))]. 128 M- and 15 T-typed strains of A-streptococci were investigated in respect of their streptolysin O production. The peak of streptolysin O production was reached after the logarithmic growth-phase and persisted for more than 24 h. The strains were classified in very weak 44% (0-1,0 E/ml), weak 30% (1,5-3,0 E/ml), medium 21% (4-8,0 E/ml) strong 5% (12-48 E/ml), 9 strains (7%) produced no detectable streptolysin O. The amount of streptolysin O necessary for antigen stimulation is discussed. A connection of growth character and enzyme production was not observed.


The pathogenicity of avian mycoplasmas.

The pathogenicity of avian mycoplasmas. Based on literature data and own experiences the author gives an outlook about pathogenicity of avian mycoplasmas. In chickens and turkeys M. gallisepticum and M. synoviae (in addition to it M. meleagridis exclusively in turkeys) are the most important mycoplasmas producing respiratory disease, inflamation of synovial membranes and other lesions. Their pathogenic effect is very much influenced by dose of agent, route of entry of microorganism, age of birds, virulence and tropism of organism as well as associated other mycoplasma or virus or bacterial or fungal infections and conditions of environment. These facts rise difficulties in serological diagnostic and erradication program. Recently ureaplasma infection was also established in chickens and turkeys which can also be associated with respiratory disease. From ducks A. laidlawii, M. anatis and various unclassified strains were isolated, among these M. anatis and unclassified arginine splitting mycoplasma strains proved to be pathogenic. In geese M. gallinarum, A. laidlawii and A. axanthum were detected. A. axanthum showed pathogenicity for goslings and goose embryos. Its effect is exacerbated by associated parvovirus infection.


The pathogenicity of mycoplasmas for plants. Many plant diseases belonging to the yellows group are believed to be caused by wall-free prokaryotes resembling mycoplasmas, which are spread by leafhopper vectors. Im most cases the evidence for mycoplasma aetiology rests upon the finding by electron microscopy of mycoplasma-like bodies in phloem tissue of diseased plants, coupled in some cases with symptom remission following treatment of plants with tetracyclines. The only plant-pathogenic mycoplasmas which have so far been cultured are the spiroplasmas (motile, helical, filamentous mycoplasmas) which cause citrus stubborn, corn stunt and probably a small number of other plant diseases. Spiroplasma citri (the citrus stubborn agent) can infect members of many plant families, and disease symptoms suggest that the organisms produce toxins. Phytotoxic substances have been detected in, and partially purified from spiroplasma cultures. The corn stunt spiroplasma does not produce toxins and probably affects plants by interfering with hormone metabolism.


Antimicrobial activity of crude juices of Allium ascalonicum, Allium cepa and Allium sativum. Crude juices of garlic (Allium sativum), onion (Allium cepa) and shallots (Allium ascalonicum) were tested in an agar diffusion test for their growth inhibitory effect on five gram negative and three gram positive bacterial species and two yeast species. All test organisms were inhibited by garlic juice, whilst onion and shallot juice showed no effect upon gram negative bacteria. Garlic juice was investigated in more detail. Addition of complex-forming agents and organic matter to the crude juice reduced its activity on all test organisms. Volatile substances showed a strong inhibitory activity after exposure for 8 hours or longer at 23 degrees C or 37 degrees C. Minimal inhibition concentrations determined in a dilution test were found to be high for gram negative bacteria and low for both yeast species. The D-values of the different test organisms in undiluted garlic juice were calculated. P. aeruginosa had a very low D-value, whilst the bacteriostatic concentration was high. This indicates a large concentration exponent of crude garlic juice for this organism. The opposite was found for S. aureus. In view of the strong antibiotic properties and the complete absence of development of resistance further investigation upon the principles of the antimicrobial activity of juices from Allium species merits consideration.


Structural changes of Toxoplasma gondii bradyzoites and cysts following therapy with sulfamethoxypyrazine-pyrimethamine: studies by light and electron microscopy. Consequences for chemotherapy. Mastomys natalensis chronically infected with Toxoplasma gondii strain ALT over two months were treated with sulfamethoxypyrazine-pyrimethamine for 10 and 25 days. 72 hours after discontinuation of therapy the animals were sacrificed. The brains were removed and, following corresponding preparation, studied for the presence of the parasite and structural changes of cysts by light and transmission electron microscopy. More or less pronounced structural changes could be found in cyst walls, bradyzoites, and in particular in the endodyogeny stages. The degree of damage proved to be proportional to the intensity of the bradyzoite metabolism. The combination of drugs used was capable of passing the cyst membrane as long as the bradyzoites maintained their metabolism irrespective of its intensity. In cysts with a largely dormant metabolism that had been subject to therapy, no micromorphological differences of the ultrastructure could be recognized when compared with untreated controls of identical age; these cysts could not be influenced by treatment.


Protective immune response in mice immunized with antigens from Trypanosoma gambiense-infected mouse blood. Immunogenicity and property of antigens obtained from Trypanosoma gambiense-infected mouse blood (IMP) were examined. A strong vaccine effect against intravenous challenges with 3 x10(3) parasites given on study day 3, 5, or 14 (day 0 = immunization) was observed in mice immunized with a combination of IMP (2 mg protein/mouse) and Freund's complete adjuvant (FCA). But when the challenge was given on day 21 or 30, per cent survival in mice dropped to the 20- and 40-per cent level, respectively. Among fractioned components of IMP, IMP-1, IMP-2, and imp-3, by gel filtration with Sephadex G-200, all of the mice immunized with IMP-1 antigen alone or together with FCA and challenged on day 5 were able to conquer intraperitoneal challenges with 1 x10(2) parasites. Mice immunized with IMP-2 or IMP-3 died within 6 days after challenge. Moreover, protection efficacy shown by IMP-1p (144,000 xg sediment of IMP-1) antigen in mice was similar to that by IMP and IMP-1 antigens. IMP-3 yielded a single precipitin line against mouse anti-IMP serum by Ouchterlony double diffusion method but this response was eliminated when the antiserum was absorbed by IMP-1p. No precipitin line was identified between mouse anti-IMP serum and IMP-1 or IMP-2. From electron microscopic observations, elements of IMP-1 and IMP-1p are possibly corresponded to the fragments of filopodia of the parasites.


Effect of intestinal flagellate Spironucleus (Hexamita) muris and of dimetridazole on intestinal microflora in thymus-defficient (nude) mice. Two groups of the intestinal microflora, the lactobacilli and the coliforms, were examined in thymus-deficient (nude) mice during the development of an experimental infection with the intestinal flagellate Spironucleus (Hexamita) muris and during the treatment with dimetridazole. The observed significant decrease in the number of lactobacilli under infection was probably due to the fact that the protozoan parasite fed on the microbes. Dimetridazole (0.3% in drinking water) did not influence the quantity of the lactobacilli but, owing to its selective killing of anaerobes and the lack of their antagonistic activity, a 100- to 1000-fold rise in the number of coliform microbes was observed. No of the drugs tested (dimetridazole, ornidazole, metronidazole, tinidazole, carbimazole BP and chlormethoxy-acridilamino-diethylamino-propanol-dihydrochliorde) was fully successful in the treatment of experimental spironucleosis in mice (Kunstýr, 1978) and it is suggested that recent reports on the therapeutic success of tinidazole in human giardiasis be treated with caution.


The role of M protein in phagocytosis. I. Activity of some enzymes in phagocytic cells during infection with Streptococcus pyogenes in vivo. The phagocytosis of two type 12 Streptococcus pyogenes strains differing in M protein presence was investigated in vivo. The rate of phagocytosis and the streptococcal viability in phagocytic cells and outside of them was studied simultanously with estimation of enzymatic activity in phagocytic cells. It was observed that M positive strain was phagocytized at lower rate and also exhibited longer viability. Decrease of lactic dehydrogenase and ATP-ase activity in phagocytes of rabbits infected with M+ strain was also detected. These results suggest that M protein disturbs phagocytosis by inhibiting their main metabolic pathway of glycolysis.


The role of M protein in phagocytosis. II. Opsonization of Streptococcus pyogenes in vitro. Opsonization of two different streptococcal group A type 12 strains was investigated. The strains differed only in M protein presence. It was observed that after the treatment of bacteria with fresh normal rabbit serum M positive strains bind to their surface IgG only whereas M negative strains solely some complement components. These results may suggest that streptococci lacking M protein are able to activate complement by alternate pathway.


Ultrastructure and viability of E. coli treated fosfomycin. In concentrations of 6 microgram/ml Fosfomycin acted bactericidal against E. coli ATCC 10536. The sensitivity of E. coli was evaluated by turbidity measurement (Table 1) and by counting colony forming units (CFU) (Table 2). Thus the bactericidal action began at different times in respect to the concentration and the method of documentation: turbidity fell 30-120 min after the administration of 6 microgram/ml and 10-30 min after 60 microgram/ml; CFU were reduced 10-30 min after 6 microgram/ml and 3-10 min after 60 microgram/ml. Before the cytoplasm and DNA-region were disorganized with reduced electron density, some elongated (up to more than 20 micron) cells occurred (Fig. 1,2). More prominent alterations in shape and ultrastructure were obvious 120 min after 6 microgram/ml (Fig. 5) and after 30 min when 60 microgram Fosfomycin per ml were administered (Fig. 3, 4), i.e. considerably later than the reduction of reproductivity.


A novel method for the production of Salmonella flagellar antigen. II. Further purification for the preparation of H antisera. A method for a simple preparation of Salmonella flagellar antigen is described. The antigen is sufficiently pure to elicit high titered H antibodies of 12,800-51,200 and O titers of less than 50. Highly motile Salmonella test strains are grown on 0.8% swarm agar and harvested with 0.05 n HCl which solubilizes the flagella. The suspension with a pH of 1.5 is kept at 4 degrees C. over night and then centrifuged at 49,000 g for 60 min. The supernatant is neutralized and precipitated with ammonium sulfate at 2/3 saturation. The resulting polymeric flagellin is submitted to a zone electrophoresis on Pevikon. Strips are cut from the "cake" and eluted. The H antigen is found on the anodic side, the O antigen remains near the trough or migrates slightly cathodically. Form 20 plates enough flagellin is collected fro the immunization of 50-100 rabbits. The Latex test proved to be especially suited for the checking of the H antigen.


[Protective role of Salmonella R mutants in Salmonella infection in mice (author's transl)]. NMRI mice were immunized with acetone-killed bacteria of 6 salmonella R mutants, 5 homologous and 6 heterologous Salmonella S forms and 3 E. coli R mutants. The animals were then challenged with graded amounts of live S. typhimurium. The results show that the protection obtained was dependent on the number of immunizing injections and on the time interval between them. Thus in the case of Salmonella R-mutants two immunizations increased the LD50 of challenge by an index of two (log 10) compaired to one immunization. A third immunization led to only a small further increase, the protection however, was longer lasting. A 3 fold immunization with two Salmonella typhimurium mutants, one SR- and one Ra form, led to a protection comparable to that obtained with S form bacteria. In contrast to the R-mutants, with Salmonella typhimurium S form a high degree of long-lasting protection was achieved already after a single immunization, and was not increased significantly by repeated injections. In animals immunized with Salmonella typhimurium S form the difference between non-lethal and 100% lethal challenge dose varied by a factor of 10 (one injection dose). In contrast, in animals immunized with Salmonella R mutants the above differences were more gradual extending over 3, 4 or more infection doses. This was also true for animals immunized with lower doses of S. typhimurium S form and for the non-immunized control animals. For comparison the protective effect of heterologous Salmonella S forms and of E. coli R-mutants was studied. These were found to be less effective in affording protection to Salmonella typhimurium than the above Salmonella R forms. The various strains used for immunization may be placed in the following sequence in order of decreasing protection: Salmonella typhimurium S form, Salmonella R-mutants, heterologous Salmonella S forms, E. coli R mutants. In a parallel investigation the antibody inducing properties of Salmonella R mutants and heterologous Salmonella S forms were studied. In all cases homologous hemaglutinating antibodies to all the strains used for immunization were detectable. In immunization with Salmonella R mutants in addition to homologous titres, agglutinating antibodies to Salmonella typhimurium S form were also produced in significant amounts. There was, however, no correlation between the time of appearance of protection and that of appearance of antibodies nor between the hight of antibody titres and degree of protection. The detection of agglutinins to the infecting microorganisms represents therefore no valid criterium for the effectiveness of R mutants and heterologous Salmonella S forms as protective vaccines. From the present results it is concluded that in addition to the O antigen one or more further cell components exist which are involved in rendering animals immune to Salmonella typhimurium and probably also to other Salmonella S form bacteria.


[Studies on the serological manifestation of the hepatitis B-virus-infections in the Republic of Liberia (author's transl)]. The prevalence of hepatitis B virus infections was examined in four groups from Liberia using radioimmunoassays for HBsAg, anti-HBs and anti-HBc. At the age of 15-19 years 90% have been infected, at the age of 40 years 100%. In a rubber plantation 30% had HBsAg, in the remaining 3 groups only 13% were HBsAg-positive. In the first group onchocerciasis was also a more frequent finding. However the parasitic infection was not the cause of the HBs-antigenemia. The HBsAg-concentration is mostly lower in the positive Liberians than in German HBsAg-carriers. Apparently the HBV caused frequently latent infections with low production of viral antigens in Liberia.


[Bacteriological studies of the intestinal content of aquatic birds, fishes, and frogs with special reference to the presence of non-cholera vibrios (NCV) (author's transl)]. In a screening study of surface waters, the authors were successful in culturing NCV in 2/3 of cases. Since these organisms are incapable of multiplication in open waters and yet were present in water samples in considerable amounts, it was postulated that they persisted in certain forms of aquatic life. To elucidate this question, the intestinal contents and in some cases, the bile of a total of 110 animals belonging to 17 different bird, fish, and frog species from different habitata were examined. From these animals, 51.8% were found to be carriers of NCV and 7.3%, of salmonella. Additionally, 4.5-15.5% were found to carry Aeromonas, Plesiomonas, Staphylococcus aureus, and Pseudomonas aeruginosa. Fish and frogs were found to offer NCV organisms possibilities to persist while migratory birds such as stock ducks import them even from tropical areas. When compared with the results of studies performed, salmonella carriers among Danube fish were found to have increased in number.


Serum IgG, IgA and IgM changes during infectious complications induced by facultative pathogenic gram-negative bacteria. IgG, IgA, and IgM concentrations were measured at 40 acute and 9 chronic patients continuously during complications induced by facultative pathogenic Gram-negative bacteria, primarily by Pseudomonas aeruginosa. On the basis of the results the sudden decrease of Ig concentrations at the onset of complications, during shock, and before death was, beside the consuming effect of antigen-antibody reactions, most probably a consequence of increased capillary permeability and haemodinamic disorders due to antigen-antibody reactions and the effect of endotoxin. It was conspicuous, that a correlation could be found between the concentration of IgM and the development or final outcome of the complications: IgM values in cases of lethal complications in the acute patients were essentially lower than in the other patients surviving severe complications, even at the early period of complications still without any clinical signs of the outcome.


Flunitrazepam versus placebo premedication for minor surgery. The clinical effects of oral flunitrazepam (2 mg on the night before operation followed by 2 mg on the morning of operation) and placebo as premedicants were tested in a double-blind study in 81 gynaecological patients. The separate or total concentrations of flunitrazepam and its demethylated metabolite in plasma (measured by gas chromatography) were correlated with the clinical effects of flunitrapam premedication, assessed both sugjectively and objectively. In most parameters tested (sleep on the night before operation, sedation, apprehension, headache, pulse rate), there was a positive, significant difference between the flunitrazepam group (n = 44) and the placebo group (n = 37). No significant difference was found between the two groups in emetic effect, excitement, systolic blood pressure increase, and vene-puncture, but the patients receiving flunitrazepam felt significantly more dizziness. The temperature of the left forefinger before, during and after the anaesthesia did not vary significantly between the two groups. There was no correlation between the plasma concentration of flunitrazepam and its demethylated metabolite (separate or total concentrations) and any of the parameters tested before induction of anaesthesia. Flunitrazepam is a new oral premedicant with prominent sedative and anxiolytic actions. When the drug is given as a sedative on the night before operation, followed by a second dose on the morning of operation, the beneficial effects last for at least 8 hours after the second dose.


Ganglionic blocking effect of some antibiotics on isolated rat sympathetic ganglion. It was shown on the isolated superior cervical ganglion of the rat that some antiobiotics exerted a blocking effect nearly as potent as that exhibited by hexamethonium or d-turbocurarine. The ganglionic blockade thus induced proved to be non-specific and due to the local anaesthetic effect of the tested drugs.


[The pneumocephalus in cranio-cerebral trauma (author's transl)]. The accident surgeon is often surprised to see unusual intracranial translucencies on X-ray films of persons with skull injuries. Inexperienced physicians are often unable to immediately identify these translucencies as air enclosures in the intracranial cavity. Physicians not acquainted with pneumoencephalography commonly employed so far in neurological examinations will find it difficult to recognize in the accumulated air the contours of the ventricular, cerebral convolution and cisternal systems. Hence, the relatively rare event of air penetrating into the intracranial space as a result of an injury, is described here on the basis of two of our patients.


[Injuries of stomach (author's transl)]. Rupture of the stomach occurs in between 0.8 to 1.7% of cases of blunt trauma of the abdomen. Isolated injuries of the stomach are rare, we have found 62 cases in the medical literature. In most cases (59--75%) the injured stomach was full. Diagnosis is by means of clinical symptoms, X-ray, and peritoneal lavage. Therapy consists of operative oversewing and possible application of anastomosis. Three of our cases are described and the literature is reviewed. The mortality rate is 32%.


[Experiences in the treatment of gas gangrene in accident surgery (author's transl)]. It is reported on 105 patients with gas gangrene. 68 cases were caused by accident, 7 of them died. Only the gas chromatographic identification of toxin in blood was needed to assure diagnosis. In 46 cases of gas gangrene localized in the lower limbs, amputation was necessary in 12 cases; in 5 cases gangrene in the lower leg, in 7 cases in the thigh. In ten cases of disease in the upper limbs three amputations were necessary. If OHP is implicated as soon as possible in the therapy of gas gangrene, in most cases local necrectomy with maintenance of the limb will be sufficient, if amputation was necessary, it was localized in the region of infection.


[Delayed splenic rupture (author's transl)]. Splenic rupture is a common injury associated with blunt abdominal trauma. In contrast, delayed splenic rupture is less frequent and comprises about 8--28% of cases of splenic rupture. The symptom free period can last for days or weeks. The mechanism is explained as follows. A rupture of the parenchyma occurs but the spleen capsula remains intact. A hematoma forms below the capsule and causes a strong overdistension of the capsule so that a bursting and release of blood into the abdominal cavity results. The mortality rate with splenic ruptures in 6--55% and with delayed splenic ruptures 14.6%. Our experiences are reviewed. After commencement of the hemorrhage therapy must consist of treatment for shock and immediate laparotomy and splenectomy.


[On the problem of industrial accidents under drug influence (author's transl)]. Industrial accidents resulting from technical defects have decreased in the last eights because of improved safety precautions. In contrast, accidents resulting from "human error" are increasing steadily. Toxicological urine analysis for drugs--directed mainly at soporifics, sedatives, tranquilizers, and pain-relievers--on 84 patients involved in industrial accidents yielded the following results. 1. Drugs were identified in 44 patients (= 52%). 2. In 13.4 patients, more than one drug was identified (= 16%). 3. Only five of the 44 patients admitted on being questioned that they had taken drugs (= 10%). On the other hand, in a control group of 47 persons who and not suffered any accident, drugs were detected in 19 cases (= 40%). The results show that the physician will have to take into account that healthy and efficient persons, too, are very often likely to practise drug abuse. It must be considered probable that this helps to promote accidents. Medical prescription, especially of neuroleptics and psychotropics, as well as of sedatives, should be practiced more.


[Olecranon fractures. A retrospective examination of surgically treated fractures (author's transl)]. Retrospective examination of 27 patients with olecranon fractures who had undergone surgical treatment showed that--in agreement with theoretical considerations--osteosynthesis via tension wiring, although suitable for proximal fractures, is unsuitable for fractures of a more distal nature. A different method must be employed for distal fractures. Additional plaster immobilisation does not exercise any influence on consolidation, nor does it affect functional rehabilitation.


[Concerning the double-side traumatic hip dislocation (author's transl)]. The double-side posttraumatic dislocation of the hip of a 17 year old moped rider is in order to discuss our concept of treatment of hip-dislocation without fracture. The result of the 2-years check-up is reported.


[The role of marginal fractures in the prognosis of ankle fractures (author's transl)]. Based on review examination of 224 patients 5 years after their ankle fractures, the authors demonstrate a significant worsening of prognosis with fractures of the anterior or posterior tibial margin. In cases without marginal fractures severe late X-ray, or clinical changes remained less than 4%, in cases with small marginal fractures their number was under 20%, with great articular surface fractures however over 30%. The unfavourable trend becomes evident even in marginal fractures not extending to the articular surface or involving only a minor part of it. It is concluded, that a dislocating force in the sagittal direction is more damaging for the joint than a force acting in the lateral direction.


[Bilateral rupture of the quadriceps tendon, a rare disease pattern (author's transl)]. The article reports on the rare bilateral rupture of the quadriceps tendon. This tendon will rupture more readily after it has undergone a degenerative change. A distinctly noticeable pit, which may be masked by a haematoma, is clinically prominent, as well as an absolute active inhibition of stretching and an abnormal lateral mobility of the patella. Immediate repair is the method of choice. The article describes the method of operation.


Utilization of the perfused stomach in anaesthetized rats to study the inhibitory effect of somatostatin in gastric acid secretion. The perfused stomach in the anaesthetized rat was used to investigate the action of somatostatin on the gastric acid secretion stimulated by gastrin, histamine and carbamylcholine. Evidence is produced that somatostatin competitively inhibits gastrin-stimulated acid secretion whereas it inhibits carbamylcholine-stimulated acid secretion by a mechanism which is non-competitive in nature and it has no action on histamine-stimulated secretion. The model of the persued stomach in the anaesthetized rat seems suitable to study the inhibition caused by drug on stimulated acid secretion.


Effect of histamine and stress on the gastric mucosal Ca2+ content during the development of gastric ulcers. The influence of histamine, its triazole derivative (3-beta-aminoethyl-1,2,4-triazole) and immobilization stress on the gastric mucosal Ca2+ content during the development of gastric ulcers in guinea pigs and rats was investigated. A considerable fall in the concentration of Ca2+ in gastric tissues of guinea pigs after administration of histamine 0.25 mg/kg, down to 80% (8.0 mumol/g), its derivative (1 mg/kg) to 72% (7.2 mucol/g) and stress to 76% (7.6 mumol/g) was recorded by atomic absorption-spectrophotometric techniques, while the calcium level in the controls stood at 9.9 mumole/g. Similar changes (90-65%) were seen in the blood plasma. In rats, the Ca2+-decreasing effects of stress ran closely parallel with increasing ulceration, and depended on the duration of stress. The immobilization of rats evoked a slight rise in the Na+ content of the gastric tissues. After 4 h immobilization, the tissue concentration of Na+ was increased to 116% of control levels. Cimetidine (100 mumol kg-1 more than 50% inhibited the development of gastric ulcers and prevented the change in Ca2+ concentration ions. Thus, the data suggest that Ca2+ ions take part not only in the regulation of secretion, but also in stress tissue dystrophy.


Histamine H1- and  H2- receptor antagonists reduce histamine-induced increases in vascular permeability and oedema formation in cat skeletal muscle. Intra-arterial fusions of histamine cause vasodilation of resistance vessels, extravasation of albumin and oedema in cat skeletal muscle. Treatment with either mepyramine or metiamide significantly reduced the extravasation of albumin and rate of oedema formation. The doses of mepyramine and metiamide used did not modify the vascular responses to bradykinin.


Stability in Newcastle disease virus-infected cells of HN protein which lost its functional activity under conditions of protein synthesis inhibition by cycloheximide. Chick embryo cell cultures were infected with Newcastle disease virus (strains Italia, Beaudette and B1), labelled with 14C-amino acids from 5 to 6 hr post infection (p.i.), incubated in chase conditions from 6 to 10 hr p.i. in the presence or absence of cycloheximide (100 microgram/ml) and analyzed by slab polyacrylamide gel electrophoresis and autoradiography. In chase experiments the HN protein was stable in all three strains. The haemagglutinating activity of cell homogenates was greatly reduced after the addition of cycloheximide in tests with Beaudette and B1 strains; treatment of the homogenates with neuraminidase from Vibrio cholerae did not influence this effect.


The effect of antibody on latent pseudorabies virus infection in vitro. Cytosine arabinoside (Ara C) inhibited the synthesis of pseudorabies virus when Vero cells were infected at a multiplicity of infection of 0.0001-0.05 PFU per cell. On removal of Ara C, infectious virus reappeared after a latent period of 3-5 days. The activation of latent virus was not influenced by elevating the temperature to 40 degrees C at the time of Ara C removal but it was prevented by antiviral antibody. When antiviral IgG was added into the culture fluid of cells either during the incubation with Ara C, or after removal of the inhibitor, the number of infectious centres was reduced to about 10%. The role of antiviral IgG in the maintenance of latency is discussed.


Influence of preincubation of primary dog kidney cell cultures on the multiplication of attenuated mumps virus. An attenuated mumps virus strain multiplied in primary dog kidney cells to significantly higher titres in cultures preincubated for 1-5 weeks at 20-25 degrees C before inoculation as compared with cultures infected immediately after their growth became confluent. The nature of this phenomenon is discussed.


Squamous metaplasia of the lung alveolar epithelium in mice after influenza virus infection. Metaplasia of the lung alveolar epithelium was observed in mice challenged with influenza virus after previous infection, and in mice repeatedly infected. Immunological factors are suggested to contribute to the development of the process.


Antiviral effect of 3-[bis-(2-hydroxyethyl)-amino]-acetophenone-[4,5-diphenyl-oxyazolyl-(2)]hydrazone (IMET 98/69) in mice. The potential in vivo antiviral activity of 3-[bis-(2-hydroxyethyl)-amino]-acetophenone-[4,5-diphenyl-oxazolyl-(2)]-hydrazone (IMET 98/69) was evaluated on model infections in mice. Animals treated subcutaneously (s.c.) with 1 mmole of the drug per kg body weight once daily for five days were significantly protected against a lethal infection with cardioviruses, Semliki forest virus and vaccinia virus. In influenza A and B virus models no antiviral activity was observed either after s.c. or oral treatment.


Serological evidence of H1 influenza virus infection among Japanese hogs. Classical H1 influenza firus infection among Japanese hogs was confirmed in 1978 by serological examination. Of 820 swine sera collected from July 1977 to February 1979 in Miyagi Prefecture, northern Japan, six sera were found to contain haemagglutination inhibition (HI) antibodies to the A/FM/1/47 (H1N1) strain. Of the six sera, one showed a significant high HI antibody titre, which was classified as IgM, to the FM1 strain, but not the other H1N1 variants. These results strongly suggest that hogs may carry an old type of H1 influenza virus. The possible role of pigs as a reservoir of human pandemic influenza strains is discussed.


Effect of terbutaline, a beta 2-adrenergic receptor stimulating compound, on cutaneous reponses to histamine, allergen, compound 48/80, and trypsin. The beta-adrenoceptor stimulating agent terbutaline (2 ng-2 microgram) injected intradermally in eight atopic subjects produced a dose-dependent inhibition of the skin reactions induced by subsequently injected allergen. After injection of 0.5 microgram terbutaline inhibition of the flare and weal responses was demonstrable throughout the observation period of 90 min. The flare response induced by histamine, the histamine liberator compound 48/80 and the proteolytic enzyme trypsin was not inhibited by terbutaline in the doses used, suggesting a selective action of terbutaline on the allergen-induced response. The weal response elicited by histamine and compound 48/80 was slightly reduced by 2 microgram terbutaline. It is suggested that pretreatment of the skin with terbutaline interferes with the ability of the cutaneous mast cells to respond to challenge with allergen and that terbutaline produces this effect in doses lower than those needed to counteract the permeability increasing effect of released mediator substances.