Changes in 2,3-DPG content and oxygen affinity in erythrocytes stored at 4 degrees C. The 2,3-DPG content of red blood cells increased within the first 24 h when fresh erythrocytes or whole blood were stored 4 degrees C. This phenomenon was strongly pH dependent. The temporary increase in 2,3-DPG was scarcely observed below pH 7.4 or above pH 7.8. In the case of whole blood, the increase was observed in CPD blood out not in ACD blood. Similar results were obtained with erythrocytes suspended in saline, when its pH was adjusted to approximately 7.6. Plasma proteins were not essential for the increase in 2,3-DPG content. Extracellular oxygen levels were continually measured in erythrocytes suspensions in order to check the changes in oxygen affinity of hemoglobin without damaging the cells. Both extracellular oxygen levels and 2,3-DPG contents were simultaneously increased by keeping fresh erythrocytes at 4 degrees C. Inhibition of glycolysis with sodium fluoride and monoidoacetic acid indicated that the in vivo steady state of glycosis in erythrocytes might be altered by chilling to make the rate of 2,3-DPG synthesis faster than that of 2,3-DPG decomposition.


Effects of two antihistaminic compounds (mequitazine, dexchlorpheniramine) on sleep. Sleep distorsion by antihistaminics. Twelve healthy subjects have been given mequitazine (two 10-milligramme doses a day), dexchlorpheniramine (two 12-milligramme doses a day) and a placebo for seven days, within a cross-over balanced design. If dexchlorpheniramine induces a significant sleep distortion (slowed REM sleep cycle and decreased amount of REM sleep), no similar trend occured with mequitazine, a result that could be dose or time related.


Metabolism of the dyestuff intermediate 2,4-diaminoanisole in the rat. 1. 2,4-Diamino[ring-U-14C]anisole.2HCl administered intraperitoneally to rats is excreted chiefly via the urine (79 and 85% of the dose in 24 and 48 h, respectively). The isotope in the faeces was 2.1 and 8.9% of the dose at 24 and 48 h. 2. The major metabolic pathway was acetylation of the amine groups(s), resulting in 4-acetylamino-2-aminoanisole and 2,4-diacetylaminoanisole. 3. Oxidate pathways yielded 2,4-diacetylaminophenol (O-demethylation), 5-hydroxy-2,4-diacetylaminoanisole (ring hydroxylation), and 2-methoxy-5-(glycol-amido)acetanilide or its isomer (omega-oxidation). 4. These major metabolites were excreted in the urine both as free and glucuronic acid conjugates.


Metabolism of 8-chloro-6-(o-chlorophenyl)-1-methyl-4H-s-triazolo [4,3-alpha] [1,4] benzodiazepine, triazolam, a new central depressant. I. Absorption, distribution and excretion in rats, dogs and monkeys. 1. Peak radioactivity in the blood was reached at 30 min after i.p. and 1 h after oral dosing of [14C]triazolam to rats. In dogs, peak blood level was observed at 30 min after oral dosing. 2. Daily dosing of triazolam to male rats for 21 days caused a gradual increase in blood level, with peak at 1 h after dosing. 3. The rate of binding of triazolam plus its metabolites to plasma protein of rats was about 30% at 15 min and 6 h. 4. In rats, the majority of the activity of the intra-intestinally administered [14C]triazolam was found in the small intestines in 6 h. 5. About 58% of the oral dose and 77% of the i.p. dose were recovered in the bile of rats in 48 h after dosing. When the bile from one rat was introduced into the duodenum of a second rat, approximately 37% was recovered in the bile of the second animal in 24 h. 6. In male rats, high radioactivity was seen in the liver, kidneys, adrenals and heart, and low in the CNS. By 96 h after dosing, radioactivity in the liver, blood and kidneys was very low, and was undetectable in other tissues and organs. Radioactivity levels in tissues after daily dosing for 7, 14 and 21 days did not differ appreciably from single administration. 7. In monkeys, activity was high in the liver, kidneys and skin following oral administration and low in the CNS. 8. After oral administration of [14C]triazolam to pregnant rats, the activity in the uterus and placenta was higher than that in the maternal blood. The activity in the foetus was low. 9. In rats given [14C]triazolam orally or i.p., 85% and 12% of the oral dose, and 82% and 14% of the i.p. dose were recovered in the faeces and urine, respectively, in 96 h. The rate of cumulative faecal and urinary excretion after repeated dosing was similar to the single dosing with 80% and 14% of the activity recovered, respectively, in faeces and urine in 6 days. In dogs, 50% of the oral dose was found in the faeces and 40% in the urine. 10. Radioactivity in the milk of rats was maximal at 4 h after oral dosing. It declined to 34% of the peak level 48 h later.


Metabolism of 8-chloro-6-(o-chlorophenyl)-1-methyl-4H-s-triazolo [4,3-alpha] [1,4]benzodiazepine, triazolam, a new central depressant. II. Identification and determination of metabolites in rats and dogs. 1. Eight metabolites of triazolam have been identified, namely, triazolam, dichlorotriazolobenzophenone (DCTB), 1'-hydroxytriazolam, dichloro-alpha-hydroxytriazolobenzophenone (1'-hydroxy-DCTB), Ar-hydroxytriazolam, 4-hydroxytriazolam, Ar-1'-dihydroxytriazolam and 1',4-dihydroxytriazolam. 2. Major metabolites found in the urine were 1',4-dihydroxytriazolam, 1'-hydroxy-DCTB and DCTB in rats; 1'-hydroxytriazolam, 4-hydroxytriazolam and conjugated 1'-hydroxytriazolam in dogs. 3. Major metabolites found in the faeces were 4-hydroxytriazolam in rats; 1'-hydroxytriazolam and 4-hydroxytriazolam in dogs. 4. Conjugated 4-hydroxytriazolam was the major metabolite in both the original and reabsorbed bile of rats. 5. Major metabolites in free form in the plasma were 4-hydroxytriazolam and 1'-hydroxytriazolam in rats; triazolam and 1'-hydroxytriazolam in dogs. 6. The major metabolite in the brain was triazolam, but those in the liver were 4-hydroxytriazolam and triazolam, and in the kidneys were 4-hydroxytriazolam and 1',4-dihydroxytriazolam. 7. Major metabolites in the urine, faeces, plasma and brain after 7-, 14- or 21-day repeated dosing in rats were not much different in type and ratio from those after single dosing. 8. Unchanged triazolam and 1'-hydroxytriazolam were the major metabolites in the plasma, placenta, foetus and amniotic fluid in pregnant rats. 9. There was no change in hepatic aniline hydroxylase and aminopyrine-N-demethylase activity from controls in rats given oral dose of [14C]triazolam for 14 days.


Hepatic microsomal N-hydroxylation of p-chloroaniline and p-chloro-N-methylaniline in red-winged blackbird compared with rat. 1. N-Hydroxylation of p-chloroaniline (PCA) and p-chloro-N-methylaniline (PCMA) was measured in red-winged blackbird (Agelaius phoeniceus) and rat (Rattus norvegicus) hepatic microsomes. 2. Redwing hepatic microsomes N-hydroxylated PCA slower than rat microsomes. Furthermore, redwing hepatic microsomes had marginal or no ability to N-hydroxylate PCMA, whereas rat hepatic microsomes N-hydroxylated PCMA at a higher rate than PCA. 3. The bird hepatic microsomes had only low or marginal N-demethylase activity with PCMA, whereas the rat hepatic microsomes could N-demethylate PCMA at a higher rate than they could N-hydroxylate it.


[Spin-lattice-relaxationtime-T1 measurements of hyaluronic acid (author's transl)]. Reductions with [3H5NaBH4 proof that the decrease in viscosity of hyaluronic acid solutions caused by lowering the pH does not depend on a depolymerisation of hyaluronic acid. At the same time investigations at different pH-values, show a sigmoide increase of the Spin-Lattice-Relaxationtime T1. This increase depends on a progressive aggregation of the hyaluronic acid molecule. The effect seems to be induced by the decrease of ionization of the carboxylgroups, by acidification of the solution.


[Investigations on the elimination of fluoride in urine after drinking waters containing different quantities of fluoride (author's transl)]. 20 volunteers were given 0.71 of water per day over a period of 10 weeks. Three different types of water were used--with traces of fluoride, with about 0.5 mg/1 fluoride and with about 11 mg/1 fluoride. A highly significant correlation was found between the intake of fluoride with the water and its elimination with the urine. About 50% of the fluoride taken in was eliminated on the same day.


Stability of patulin at ph 6.0-8.0 and 25 degrees c. Patulin was tested for stability at pH values of 6.0, 6.5, 7.0, 7.5, and 8.0, using Sörensen's phosphate buffer at 25 degrees C. Patulin was determined by high-performance liquid chromatography. When the percentage of patulin remaining was plotted versus reaction time, apparent first-order reaction plots were obtained. Reaction rate constants for disappearance of patulin ranged from 1.1 x 10(-2) h at pH 8.0-5.3 x 10(-4) h at pH 6.0. Values for half-life were calculated and ranged from 64 h at pH 8.0 to 1310 h at pH 6.0.


Biosynthesis of fat in surface culture of a local strain of Aspergillus flavus. An Aspergillus flavus strain isolated from Egyptian soil produced fat in appreciable amounts. General evidence for the operation of the tricarboxylic acid cycle in this organism has been ascertained by the detection of citric, malic and fumaric acids in the metabolized culture solution. Maximum fat yield was attained after seven days of incubation. The lower intial pH value of the media favoured the fat obtained from the felts and raised its acid value. When the felts were sterilized in their acidic metabolism solutions increased the acid values of the fats over those of fats extracted from felts sterilized in distilled water. The felts autoclaved for the longest time produced the highest yields of fat with the highest free acidity. The employment of calcium carbonate in the nutrient solutions raised appreciably the acid values of the fats and suppressed the other metabolic activities.


[Surgical treatment of hiatal hernias (author's transl)]. The diagnosis "hiatal hernia" does not equate with surgery, but if it is combined with disturbed function of the gastrooesophageal transitional area or reflux oesophagitis it needs therapy. Therefore, the diagnosis has to be made with care. Based on over 800 cases the intraluminal layered pH-metry proved to be a very helpful method. Paraoesophageal hernias should be surgically treated due to their tendency towards strangulation and incarceration. From 1956 to 1976 287 patients suffering from hiatal hernia were operated on, mortality rate and late results are analysed.


[The effects of Pavulon (pancuronium bromide) on maternal circulation and metabolism as well as on fetal metabolism and postnatal condition at Caesarean section (author's transl)]. The effects of pancuronium bromide (Pavulon) on maternal circulation and metabolism as well as on fetal metabolism and postnatal conditions were studied in 13 women in late pregnancy (between gestational weeks 33 and 40) requiring Caesarean section in general anaesthesia. A comparison with results of 50 spontaneous deliveries without analgetics was performed. The average dosage of 4 mg did not effect the maternal blood pressure, fetal muscle tonus and cardiorespiratory adaption of the newborn. According to general anaesthesia we found in acid-base status a pH decrease with respiratory acidosis in comparison with spontaneous deliveries without anaesthetics, but pH and pCO2 were normalized 30 min after delivery. On the contrary, the oxygen tension were higher as at delivery as 30 min after delivery by Caesarean section. Although 1 minute Apgar score was lower than after spontaneous delivery the heart rate and frequency of ventilation were normal in every time and in the following minutes Apgar score was 7 to 10, too. An effect of pancuronium bromide to maternal or fetal carbohydrate metabolism could not be found. The less side effects on maternal cardiovascular system and the missing influence in postnatal condition recommand pancuronium bromide as a suitable relaxant in obstetrical anaesthesia, too.


[Immunodiffusion methods of studying the F-fraction antigens obtained from group A streptococci]. F fractions, obtained by the extraction of cultures of group A streptococci with distilled water at different pH, were studied by immunodifusion methods and subjected to chemical analysis. F fractions were shown to contain polyglcerophosphate, antigen E4 and in some cases group polysaccharide. Besides, F fractions were found to contain an antigen insensitive to trypsin and identical to one of the antigens of the thermostable fraction, as well as an antigen sensitive to the action of proteolytic enzymes and common to various types of group A streptococci. The antigen sensitive to the action of proteolytic enzymes were identical to one of the antigens showing no type specificity and contained in HC1 extracts prepared from group A streptococci. In grouping and typing group A streptococci the present of some F fraction antigens unrelated either to polysaccharide or to M substance should be taken into consideration. The antigens of F fraction have no protective properties.


[Changes in the clinical picture and course of psychoses as a result of massive psychopharmacotherapy and their role in improving treatment services]. An analysis of certain regularities in drug pathomorphosis of psychoses in the form of transitions from psychotical states to pseudoneurotic showed a slowing in their progression, changes in the syndrome structure, an increase in the amount of incomplete or reduced conditions. This circumstance prompted reconsideration of some routine therapeutic approaches. The main recommendations include restriction of neuroleptics, expansion of the diagnosis of depressions, the use of methods of intensive psychopharmacology in combination with active rehabilitation, as well as introduction of new forms of organizational aid.


Partial purification and some properties of a liver alkaline ribonuclease from the frog Rana esculenta. 1. RNAases varying in pH optimum, activation with pCMB, sensitivity towards temperature and acid treatment, as well as electrophoretic mobility were found in Rana esculenta liver extract. 2. Of the three activity peaks of alkaline ribonuclease separated on CM-cellulose with 2000-fold purification, RNAase of peak C is thermo- and acid-stable and exhibits specificity for pyrimidine bases, preferring poly(U) over poly(C). 3. Differences in the specific "inhibitory effect" of frog liver supernatant on the frog liver alkaline RNAase were observed.


Iodoamino acid synthesis in thyroid lobes in vitro with excellent yield of iodothyronines. Thyroid lobes of male Sprague-Dawley rats on an iodine-sufficient diet were incubated in our improved in vitro system with 0.01 microM 127I and 5mU/ml of bovine TSH. Thyroidal 131I-uptake and the relative incorporation of iodine into iodothyronines increased with time. The average yield of each iodoamino acid after 8 h of incubation was: monoiodotyrosine 28.0%, diiodotyrosine 46.5%, triiodothyronine 1.9% and thyroxine 13.9%, which showed a striking resemblance to the values obtained in vivo. The yields of iodotyrosines and iodothyronines, the latter in particular, were strikingly high, and this system is considered to be useful in the study of thyroidal iodine metabolism. Effects of TSH, temperature and pH of the medium were examined and a unique effect of pH was observed on the iodoamino acid synthesis. As the pH was elevated from 6.8 to 7.9, 131I-uptake, MIT/DIT ratio, T4/DIT ratio and T3/T4 ratio increased. The effect of slightly alkaline pH was considered to be similar to that observed in iodine-deficiency. It was found that the rubber stoppers which are commonly used in short-term incubation contain a kind of potent inhibitor of thyroid hormone synthesis. The pattern of inhibition was similar to that of thionamide compounds.


Dixyrazine (Esucos) as premedication for esophagogastroscopy. A controlled double-blind trial. Dixyrazine (Esucos) as premedication for esophagogastroscopy was studied in a double-blind trial with diazepam and atropine in 321 successive endoscopies. It was established that dixyrazine was fairly well tolerated, regurgitation was significantly reduced. A distinct antiemetic effect was observed compared with diazepam; the difference was statistically significant in the male patients. Dixyrazine may be regarded as a fairly good alternative premedication for esophagogastroscopy.


Electrometric measurement of canine pancreatic tissue pH under conditions of preserved circulation and of ischaemia. Canine pancreatic pH was measured by an electrometric method, which is described in detail. 60 measurements carried out in neuroleptanalgesia of the animals gave a mean figure of 7.29 +/- 0.10 for pancreatic pH in situ. For arterial blood pH in the same animals the mean value was 7.22 +/- 0.08. The difference between pancreatic and arterial blood pH is significant. Anaesthesia of 3 hr duration produced no significant change either in pancreatic pH or in arterial blood pH or in the serum amylase and serum lipase levels. Vascular isolation of the pancreas and adjoining duodenal segment was produced in 13 animals. In 10 of these ischaemia induced by clamping of the arterial pathways for 1 hr resulted in a fall of pH by 0.65 +/- 0.21. Restoration of blood-flow at the end of the first hour was followed by a return of pH to the original values. The 3 control animals revealed no significant changes in the pH and enzyme values.


Study of pancreatic tissue pH in the early stage of experimental acute pancreatitis. Pancreatic pH was measured electrometrically over a period of 3 h in 34 dogs with acute necrotic pancreatis. The disease had been induced with sunflower oil in 10, with Na-taurocholate in 10 and with hen's egg yolk in 10 animals. Four dogs served as controls. The pH of the pancreatic tissue changed differently in the different groups, in accordance with the different pathomechanisms. Injection of sunflower oil was followed by a protracted acidosis of pancreatic tissue, that of taurocholate by a transitory moderate decline of pH. Egg-yolk produced an evanescent, slight fall in pancreatic pH, followed by complete normalization within a few minutes. The differences between the initial and the 3-h values attain the level of significance only in case of sunflower-oil pancreatitis.


Comparative potency and speed of onset of fazadinium and d-tubocurarine. The potency and speed of onset of fazadinium and d-tubocurarine have been compared at three cumulative doses. Wtih thiopentone as the induction agent, the dose ratio fazadinium/d-tubocurarine ranged from 1.2 to 1.3 for single twitch reduction and from 1.1 to 1.2 for reduction of tetanus. The times taken for the development of 50% and 100% effect after each dose increment were not significantly different for the three doses of fazadinium and the 2nd and 3nd doses of d-tubocurarine. However, the 1st dose of d-tubocurarine was markedly slower than fazadinium to achieve a 50% and 100% effect.


Developments in understanding the physiology and pharmacology of parkinsonism. While the era of major advances in understanding and treating parkinsonism seems to be over, steady progress is being made in elucidating physiological and pharmacological aspects of extrapyramidal function. The dramatic impact of levodopa therapy has been followed by the recognition of serious limitations to its long-term use, which provides a continuing stimulus for efforts to analyze the physiological and pharmacological properties of the basal ganglia and substantia nigra. There are reasonable grounds for the hope that this research will lead to significant developments in therapy.


Uptake of putative neurotransmitters in the organ of Corti. In vitro uptake of putative neurotransmitters into the organ of Corti of the guinea pig was studied by autoradiography. After incubation in 3H-glycine the label was heaviest over the inner hair cell, but was not confined to the synaptic region of the cell. After incubation in 3H-GABA, 3H-glutamate and 3H-aspartate, heavy labeling was seen over the fibers and terminals of the efferent olivocochlear bundle. Leucine, an amino acid not thought to be a neurotransmitter, was uniformly taken up by all cochlear structures. The fact that GABA, glutamate and aspartate are taken up into efferents, which are almost certainly cholinergic, suggests that high affinity uptake of these substances is not restricted to terminals in which these substances are released as neurotransmitters.


Periarteritis nodosa in spontaneously hypertensive rats -- incidence and distribution. SHR rats (Nihon Rat Inc.) were used to study spontaneous arterial lesions morphologically resembling human periarteritis nodosa (PN). Male SHR rats (159) developed PN in 76.1%, whereas females (39) in 10.3% during a period of 2 to 15 months of age. The frequency of PN in male SHR rats tended to increase with ageing and reached 100% at 9 months of age. PN lesions were widely distributed with only the lungs, brain and aorta being spared. PN in females was restricted to the tongue, parametrium and mesenterium. Male SHR rats with hypertension of more than 180 mm Hg showed PN in 81.7%, whereas in females with the same hypertension PN was found in only 17.4%. Although there was apparent sex difference in the incidence and background of hypertension, male SHR rats might be a useful animal model of human PN.


Rheumatoid arthritis with systemic necrotizing arteritis. An autopsy case of rheumatoid arthritis with active polyarthritis, systemic necrotizing arteritis, pleuritis, pericarditis, rheumatoid nodules in a few organs and a healing gastric ulcer was reported. Histologically, systemic necrotizing arteritis was characterized by vascular changes of the following three types: Granulomatous arteritis with a characteristic arrangement of mesenchymal cells forming a palisade around coagulation necrosis of media and some of them formed a rheumatoid nodule-like lesion in the wall (RA type); Fibrinoid arteritis very similar to the Kussmaul-Maier type periarteritis nodosa (PN type); and chronic arteritis with endarterial proliferation (Ep type). Although it is hard to distinguish arteritis of PN type from the Kussmaul-Maier type periarteritis nodosa, arteritis of RA type with rheumatoid nodule-like lesion in the wall may be interpreted as an extremely developed form of vasculitis in rheumatoid arthritis.


Effects of adrenergic beta-blockers and a membrane stabilizing agent on ouabain-induced cardiac arrhythmias in anaesthetized guinea pigs. The antiarrhythmic effects of dl'propranolol, d-propranolol, metoprolol and lidocaine against ouabain-induced cardiac arrhythmias were studied. It was found that contrary to earlier findings in the dog, the effects of the adrenergic beta-blockers against ouabain-arrhythmias in guinea pigs were due to beta-blocking activity and not the membrane-stabilizing activity of the compounds. The cardioselective beta-blocker, metoprolol, was more or equally effective as dl-propranolol against ouabain-induced arrhythmias in guinea pigs.


Mutagenic activation of tris(2,3-dibromopropyl)phosphate: the role of microsomal oxidative metabolism. The flame retardant tris(2,3-dibromopropyl)phosphate (Tris-BP) is converted to products which are mutagenic for Salmonella typhimurium TA 100 in the presence of rat liver microsomes, NADPH and oxygen. Other bromopropyl-compounds were also mutagenic; 2,3-dibromopropene and 2,3-dibromopropionic acid were directly mutagenic, whereas 2,3-dibromopropanol and tris(2-bromopropyl)phosphate were weakly mutagenic after addition of liver microsomes and cofactors. Typical in vivo and in vitro inhibitors of cytochrome P-450 inhibited Tris-BP mutagenicity. The effects of inducers of cytochrome P-450 on Tris-BP mutagenicity was dependent on the concentration of mutagen and microsomal protein in the assay, indicating complexity in the kinetics involved when dealing with possible multiple pathways that lead to mutagenicity. Addition of glutathione strongly inhibited Tris-BP mutagenicity. It is suggested that Tris-BP is oxidized to a reactive electrophile, possibly the 2-keto derivative, which could react with nucleophilic groups in DNA and thus lead to mutagenic events.


Inhibition of apomorphine-induced climbing in mice by cholinergic drugs and neuroleptics. Apomorphine (ap) was administered subcutaneously to mice kept in individual cages. Ap elicited an abnormal vertical climbing behaviour. The muscarinomimetics physostigmine and oxotremorine as well as the neuroleptics clozapine and haloperidol inhibited the climbing produced by ap 1 mg/kg. A small inactive dose of physostigmine potentiated the effect of clozapine but not that of haloperidol. The anticholinergic atropine antagonized the effect of physostigmine, oxotremozine, clozapine and haloperidol. The climbing behaviour produced by ap is presumably due to stimulation of dopamine receptors and this effect can be antagonized either by blockade of dopamine receptors or by activation of muscarinic receptors. Some lines of evidence suggest that the ap-inhibitory effect of clozapine may be partly due to a muscarinomimetic effect.


Naloxone: a potent ketobemidone antagonist in man. Naloxone has been accepted as a potent antagonist towards several narcotic analgesics, e.g. morphine, heroin and pethidin. Its effect as an antagonist and its potency against ketobemidone have not been tested in man. We have described the antagonistic effect of naloxone towards the respiratory depression caused by the administration of ketobemidone to patients anesthetized with N2O/O2 and methohexitone.


Fluoride inhibition of protein and DNA synthesis in cells in vitro. Fluoride concentrations at and above 0.9 mM caused a progressive, concentration-related inhibition in the incorporation of both 14C-leucine and 3H-thymidine in LS cells incubated in medium with serum. The incorporation of leucine was more affected than that of thymidine. Lowering the pH enhanced the effect of fluoride on both. Removing serum from the incubation medium changed the effect of fluoride, particularly at low pH (7.0). Incorporation of leucine was then stimulated by low fluoride concentrations (0.5 and 0.9 mM), and the effect on thymidine incorporation was eradicated up to 1.3 mM-NaF. No differences were found in the pool and the specific activity of 14C-leucine in the fluoride exposed cells compared to control cells without fluoride (incubated at pH 7.4 in medium without serum). The cellular pool of 3H-thymidine decreased markedly during the incubation period, somewhat less in the fluoride exposed cells than in the control.


Influence of neural and humoral beta-adrenoceptor stimulation on dynamic myogenic microvascular reactivity in cat skeletal muscle. Analysis of myogenic microvascular reactivity in terms of its recently described prominent dynamic component was performed before and during graded sympathetic stimulation and catecholamine infusion. Phenoxybenzamine and propranolol were used to differentiate between alpha- and beta-adrenoceptor effects. The study first confirmed previous findings of a beta-adrenergic inhibitory component in the neural control of microvascular resistance which attenuated the alpha-adrenergic constriction. The results concerning the interaction between adrenergic and myogenic control mechanisms corroborated the conclusion that the sympathoadrenal system, via its beta-adrenergic link, exerts effective inhibitory action on myogenic excitatory reactions. As regards the neural control, its beta-adrenergic component seemed to quite precisely compensate for the reinforcing effect on the myogenic constrictor response which results from increased vascular tone per se (in this case caused by alpha-adrenergic constriction), interpreted as a physical 'gain' effect inherent in the inverse fourth power relationship between radius and resistance. The latter complicating factor, which implies non-linearity in integrated peripheral resistance control, was thus revealed only after beta-blockade, but not on the vascular bed with intact adrenoceptors, where a given transmural pressure stimulus evoked an almost equally large myogenic constrictor response irrespective of the prevailing level of vascular tone. The beta-inhibitory action of blood-borne noradrenaline was similar to the neural one, whereas that of adrenaline was more effective, causing decline of myogenic reactivity below control.


Radiation sensitivity change of hemopoietic cells induced by hydroxyurea. Hemopoietic tissues of mice contain cells capable of proliferation and differentiation to form endogenous spleen colonies (Endo-CFU-S) in irradiated animals. Hydroxyurea (HU) given before irradiation of C57BL mice for endogenous CFU assay increased the number of surviving CFU-S twofold. Either HU or HSATT given after the initial stimulus abolished this rise. In vivo and in vitro 'suicide' assays of spleen cells indicated that cells were stimulated by the HU or the initial stimulus to enter into DNA synthesis shortly after stimulation. The resting CFU cell population appeared to be positioned close to DNA-S phase and responded to the stimulus by entry into S phase. Whole body irradiation at intervals after HU revealed a changing radiation sensitivity of the endogenous CFU-S consistent with drug-induced progression with decreased radiation sensitivity of the S phase cohort of cells.


Biliary and pancreatic secretions in abdominal irradiation. The biliary and pancreatic secretions have been determined in patients given pelvic or para-aortic irradiation, with a dose of 50 Gy in the former group and between 36 and 40 Gy in the latter. A test meal containing polyethylene glycol (PEG) as reference substance was used. Each sample of the duodenal content was assayed for volume, PEG content, amylase and trypsin activity, pH and biliary secretion. No significant modifications of biliary and pancreatic secretions were demonstrated after irradiation, suggesting that these functions are not involved in the pathogenesis of the malabsorption radiation syndrome.


Motor reactivity of isolated heart of grass-snake (Natrix natrix L.) effects of temperature and pH. It was demonstrated that isolated heart of the grass-snake perfused with a fluid of properly chosen components can pulsate without abnormalities for at least 12 hours, and the rate of its contractions depends, in a high degree, on the temperature. This relationship is a logarithmic one, although in the temperature range from 10 degrees to 22 degrees C the regression is linear. The highest temperature at which the heart rhythm was still regular was 34 degrees C. The isolated heart contracted rhythmically and normally even when pH of the nutritive solution differed considerably from the physiological value, showing greater tolerance of contractility in the case of solutions in the alkaline range of pH. It seems that the pH range from 6.5 to 9.5 is the optimal one for maintaining the function of grass-snake heart.


Properties of erythrocyte catalase from heterozygotes for Japanese type acatalasemia. The level of blood catalase activity in heterozygotes for Japanese type acatalasemia was demonstrated to be about half of normal levels by means of titration and spectrophotometric methods. A distribution plot of catalase activities in heterozygous blood was completely separate from that of normal blood. Comparative analysis of the partially purified erythrocyte catalase preparations obtained from normal and heterozygous individuals revealed no distinct differences between them regarding stability to heat, sodium dodecyl sulfate and some enzyme inhibitors or pH dependency. The erythrocyte catalase in heterozygotes for Japanese type acatalasemia contains about half the normal specific activity and as stable as that in normal individuals.


Determination of prekallikrein in plasma by means of a chromogenic tripeptide substrate for plasma kallikrein. A method for plasma prekallikrein determination utilizing a chromogenic tripeptic substrate is presented. The method has a good reproducibility and can easily be automized. Several parameters have been optimized. By using mixtures of deficient plasmas and pooled normal plasma or purified factors it was proved that prekallikrein was the factor determined and that more than 10% (of normal plasma concentration) of FXII and HMW kininogen were essential for the activation of prekallikrein in our method. Further experiments showed that the method was fairly selective and was not influenced by inhibitors present in normal plasma. The later finding was attributed to the high dilution of plasma made possible by using a potent activator and a sensitive substrate.


[Effect of vitamin D and vitamin E on the erythrocyte membrane. I. Effect on in vitro osmolar resistance and lysis]. As in the case of retinol, low doses of cholecalcipherol and alpha-tocopherol "in vitro" increase the osmotic resistance of red blood cells, while high doses have a lytic effect on the erythrocytes of various animal species (e.g.: man, sheep, rabbit, guinea-pig, mouse, rat) with the exception of the chicken. The haemolytic effect of cholecalcipherol is less intense than that of retinol; alpha-tochopherol, while causing even less haemolysis than cholecalcipherol, involves a remarkable loss of K+ from the red cells. Besides these quantitative differences, the mechanism of action of the three vitamins seems somewhat different, as shown by modifications of the suspension medium (e.g.: pH, temperature, presence of proteins and reducing substances) or by treatment of the red cells with trypsin. Our results therefore essentially confirm the hypothesis of Dingle and Lucy of common mechanism of action of liposoluble vitamins on biological membranes.


[Regulation processes in biological systems. II. Role of compartmentation and of organized multienzyme systems]. The picture, emerging from the experimental results on the physical association of multienzyme systems, is that the true physiological significance of the aggregated state can be understood only if it is correlated to the structural and functional integration of the cellular metabolic framework as a whole. The enzyme clusters exhibit two distinct functional properties. The first is the spatial translocation of intermediate substrates, the effect of which may be viewed as metabolic "channelling" or "vectorial catalysis" if the enzyme clusters are arrayed in some manner in the cell. The second is the coordinate regulation which represents an efficient and economical mean of controlling two or more functionally related enzymes. The common element to these two properties is the spatial character, which is potentially present in the function and the regulation of the intermediary metabolism. The biological systems, and metabolism in particular, exhibit both stability and variability; the latter sometimes assumes the character of periodicity. Whether the oscillations have a definite importance at the level of the intermediary metabolism itself, may well be questioned; the oscillatory faculties may rather serve as elements to be used in more complex functions of the biological systems. A thorough understanding of the role of clustered multienzyme systems and of the oscillatory phenomena in cellular metabolism demands a clearer physicochemical picture of the dynamic state of the living cell than we have at present. For this reason some of the generalizations derived from in vitro studies of single, isolated enzyme activities are not justified.


Newcastle disease virus-specific RNA: an analysis of 24 S and 35 S RNA transcripts. The denaturation of Newcastle disease virus-specific 24 S and 35 S RNA by heat or formamide treatment led to a shift of a large part (60--80%) of RNA into the 18 S zone. The remaining 20--40% could not be dissociated further by repeated denaturation or by centrifugation in dimethyl sulfoxide-sucrose gradient. Hybridization-competition analysis revealed that the majority (approximately 75%) of the non-dissociable 35 S RNA and almost all the material present in the non-dissociable 24 S RNA were represented by nucleotide sequences homologous to 18 S RNA. On the other hand, the non-dissociable 35 S RNA lacked some of the sequences present in 18 S RNA, since no more than 45% of the labelled 18 S RNA could be displaced from the hybrid by an excess of unlabelled non-dissociable 35 S RNA. The possible origin of 24 S and 35 S RNA is discussed.


Cellular localization of Saint Louis encephalitis virus replication. Replication of Saint Louis encephalitis (SLE) virus was inhibited when PS cells were treated with actinomycin D, daunomycin or cordycepin during the first 9 hr after infection. Autoradiography of SLE virus-infected pulse labelled cells demonstrated that viral RNA synthesis is localized within the nuclear area. Nuclei purified from cells after 12 hr of infection contained heterogeneous 20 S to 26 S viral RNA but no SLE virus genome sized 43 S RNA. Later during infection, nuclei isolated from infected cells contained large amounts of 43 S and 20 S to 26 S RNAs. The 43 S viral RNA present in cells late in infection could not be removed with 1% Tween 80: Nonidet P 40. Purified nuclei isolated from cells early in infection supported the synthesis of 43 S virion RNA in the absence of cytoplasmic factors. The cytoplasmic membrane fraction prepared from cells early in infection contained heterogeneous 10 S to 26 S RNA species; later during infection these membranes contained viral 43 S, 26 S to 30 S and 4 S RNA. These results suggest that the nucleus is an important site of early viral synthesis.


Role of calcium dependent regulator protein (CDR) in inhibition of 3',5'-c AMP-phosphodiesterase by influenza virus. I. Isolation and purification of CDR and CDR-dependent 3',5'-c' AMP-phosphodiesterase from chick embryos. Calcium-dependent regulator protein (CDR) and CDR-dependent 3',5'-c AMP-phosphodiesterase were isolated and partially purified from 12-day chick embryos. Some basic properties of the preparations obtained were described. Native (infectious) but not noninfectious (heat-inactivated) influenza virus in the presence of CDR and ATP reduced the activity of CDR-dependent phosphodiesterase.


Role of calcium-dependent regulator protein (CDR) in inhibition of 3',5'-c AMP-phosphodiesterase by influenza virus. II. Kinetic studies on inhibition of CDR-dependent phosphodiesterase by influenza virus. As revealed by spectrophotometry, native but not heat-inactivated influenza virus in the presence of ATP reduced the activity of calcium-dependent regulator protein-stimulated 3',5'-c AMP-phosphodiesterase (CDR-PDE). ATP could be partially replaced by ADP but not by AMP. The degree of CDR-PDE inhibition increased with increasing virus concentration. But at very high virus concentrations the rate of 3',5'-c AMP hydrolysis by CDR-PDE was not linearly dependent on time. At appropriate virus concentrations the degree of inhibition of CDR-PDE activity remained unchanged for the whole reaction time.


Effects of cytosine arabinoside on the incorporation of pyrimidine nucleosides into hamster cells transformed by herpes simplex type 1 and type 2 viruses and by human cytomegalovirus. The incorporation of 3H-thymidine and 3H-deoxycytidine into acidoprecipitable fraction of hamster cells transformed by herpes simplex viruses type 1 and type 2 and of 3H-thymidine into hamster cells transformed by human cytomegalovirus was found to be resistant to the action of cytosine arabinoside. More 3H-thymidine was incorporated into these cells in the presence than in the absence of the drug. Similar stimulaton of 3H-thymidine uptake could be achieved by using unlabelled deoxycytidine instead of cytosine arabinoside. Incorporation of both nucleosides into spontaneously and SV40 transformed cells was efficiently inhibited by the drug.


Cross-neutralization between vesicular stomatitis virus type Indiana and Chandipura virus. Using highly potent immune sheep sera, it was possible to demonstrate that: (1) Two rhabdoviruses, classified in the Vesiculovirus genus on morphological grounds but previously considered unrelated, viz., the vesicular stomatitis virus type Indiana (VSV), and Chandipura virus (ChV), show a low-level, but distinct cross-neutralization. This was, in most combinations, considerably increased by complement. (2) The species of cells used for growing the viruses for immunization and for neutralization tests, influenced the level of cross-neutralization. (3) No cross-reaction between VSV and ChV could be detected in the immunodiffusion reaction. (4) Immune sera, raised in sheep by immunization with the two purified rhabdoviruses contained complement-dependent cytotoxic antibodies specifically reacting with the cell species used for growing the viruses.


Quantitative and rapid assays of togaviruses by immunofluorescence. For the quantitative assay of selected togaviruses, suspensions of BHK cells were inoculated with virus and grown in spinner cultures. At intervals, dependent on the growth characteristics of the viruses, about 10(3) cells were centrifuged on to microscope slides and then stained with fluorescent antibody. For rapid demonstration (2--3 hr) of specific viral antigens, virus was bound in successive dilutions onto microscope slides and stained. Binding of specific anti-virus antibodies in both methods, was determined either by a second labelled antibody against complement or by labelled protein A. By these methods the determination of viral antigens (Sindbis, Semliki Forest, West Nile and hog cholera viruses) was independent from the source of immune sera.


Early events in non-lethal rabies infection. Inoculation of sublethal doses of rabies virus strains isolated from small wild rodents resulted in non-lethal infection of white mice. During the first 48 hr after inoculation the virus neutralizing and protection activities in mouse sera and brain suspensions increased, followed by a transient decrease on the 3rd and 4th day. In some cases there also occurred transient multiplication of virus, which retained a relatively high infectivity for mice.


Newcastle disease virus-specific RNA: hybridization-competition of the non-dissociable 35 S RNA with individual 18 S RNA species. The non-dissociable fraction of Newcastle disease virus- (NDV-Y specific 35 S RNA competed efficiently with two individual 18 S RNA transcripts in hybridization-competition experiments with 50 S virion RNA. The third 18 S component could not be displaced from the hybrid by an excess of non-dissociable 35 S RNA.


Decrease of sensitivity to cell-growth inhibitory effect of interferon in human embryo cells after infection with SV40. No changes in sensitivity of human embryo cells (HEC) to the antiviral action of interferon early (i.e. up to 17 days) after infection with simian virus 40 (SV40) could be detected. At the same time the sensitivity of cells to the cell-growth inhibitory effect of interferon decreased considerably. The changes in sensitivity of HEC to interferon action occurred during 5 successive passages following the infection with SV40 and remained on a similar level thereafter. During this period, no morphological alterations of cells were observed.


Pharmacology of continence and micturition. Knowledge of the neurophysiology and nueropharmacology of the lower urinary tract is necessary for proper utilization of drugs to manage disorders of continence and micturition. It is also important in understanding the urologic manifestations of common drugs used for nonurologic indications. In general, bladder activity is augmented by cholinergic (muscarinic) drugs and is depressed by antimuscarinic drugs. Drugs with alpha-adrenergic activity tend to increase bladder outlet resistance, while drugs with alpha-adrenergic blocking activity tend to decrease bladder outlet resistance.


Cardiac hypertrophy in early hypertension. Studies of cardiac hypertrophy in spontaneously hypertensive rats have indicated that left ventricular hypertrophy occurred even in the prehypertensive stage. These findings suggested that other factors besides blood pressure levels, and including possibly a genetic predisposition to myocardial hypertrophy, could play a role in structural cardiovascular alterations in spontaneously hypertensive rats. More recent studies have confirmed these anatomic results; left ventricular hypertrophy was vectorcardiographically detected even in the prehypertensive stage in voth young stroke-prone rats and stroke-resistant spontaneously hypertensive rats. Further, a close relation was found between degree of left ventricular hypertrophy and vascular hypertrophy or hyperplasia; this suggests that early detection of left ventricular hypertrophy may be a useful indicator of the incipient stage of structural vascular changes in genetic hypertension.


Serum diazepam concentrations in overdose. Their significance. Total serum benzodiazepine concentrations were correlated with clinical manifestations in 93 cases of diazepam overdose. Diazepam and nordiazepam were also each separately determined in 101 serum specimens from cases of diazepam overdose, including 27 cases from the aforementioned clinical correlation study. In addition, serum nordiazepam concentrations were measured in five cases of chlorazepate overdose. Concentrations of total benzodiazepine ranged from 1 to 22 microgram/ml. All patients survived with supportive therapy only. Each of the 25 patients who had ingested only diazepam was awake or in grade 0 coma, even when drug concentrations were ten-fold greater than the accepted upper limit of the therapeutic range. None of the patients who had ingested only diazepam needed hospitalization; all were discharged from acute medical care after a period of emergency room observation. The ratios of parent drug to N-desmethyl metabolite (nordiazepam) in those overdose specimens analyzed by gas chromatography averaged 3:1. This high ratio may be useful in differentiating acute overdose from high concentrations resulting from chronic therapy. Although determination of diazepam concentrations aid in establishing that an overdose has occurred, when more than grade I or II coma is present, other drugs or an alternative explanation should be sought, regardless of the drug concentration.


Immunoblastic lymphadenopathy, systemic lupus erythematosus, and related disorders. Possible pathogenetic pathways. The authors discuss the hypothesis that the spontaneously developing (angio-) immunoblastic lymphadenopathy of man as well as the various autoantibodies and constitutional symptoms accompanying this disease may be mediated by different reactions of T lymphocytes toward adjacent lymphocytes and macrophages, whose membranes were rendered incompatible by certain viruses or sensitizing drugs such as the antiepileptic compound diphenylhydantoin. This concept is based on two different lines of experimental evidence: (1) results obtained with animal graft-versus-host reactions, in which immunoblastic lymphadenopathy, angiogenesis, dermatitis and multiple autoantibody formation are known to be induced by reactions of parental T lymphocytes toward genetically foreign structures of the major histocompatibility complex; (2) experiments pointing to an essential similarity in T-cell reactions toward genetically foreign major histocompatibility structures on the one hand and self-major histocompatibility structures that were rendered "foreign" by viruses or chemicals on the other hand; (3) recent findings in mice that demonstrate a T-cell-dependent lymphoproliferation after the administration of diphenylhydantoin.


Susceptibility of streptococci to newer tetracyclines and cephalosporins and to other antimicrobial agents. Two hundred and thirty-nine strains of Streptococcus including 71 strains of Group A, 81 strains of Group B, 69 strains of enterococci, and 18 strains of S. pneumoniae were tested against 12 antimicrobial agents using an agar dilution method. Cefamandole was the most active cephalosporin tested. Doxycycline and minocycline were more active than tetracycline, although the tetracyclines were considerably less inhibitory than the cephalosporins. Regression line analysis of zones of inhibition versus minimal inhibitory concentration values for tetracycline and minocycline showed the tetracycline disc to be unacceptable for predicting the susceptibility of the Group A Streptococcus to minocycline. Minimal inhibitory concentrations for clindamycin, erythromycin, chloramphenicol, nitrofurantoin, and spectinomycin are also given.


The effect of acute maternal hemorrhage on the release of catecholamines in the pregnant ewe and the fetus. Five chronically instrumented pregnant ewes and their fetuses were studied to assess the effect of acute maternal hemorrhage. The hemorrhage was produced in two stages; during the first stage 15% of the total maternal blood volume was removed, and then in a second stage an additional 15% was removed. Biophysical and biochemical variables were monitored. Plasma dopamine, norepinephrine, and epinephrine were determined by a sensitive radioenzymatic assay. A significant rise in maternal and fetal catecholamines was observed following an estimated maternal blood volume depletion of 30%. During a 15-minute recovery period, the maternal catecholamine concentrations returned to normal, while the fetal concentrations remained elevated. These changes were accompanied by significant changes in maternal and fetal homeostasis. The significance of these findings is discussed.


Permanent changes of ventricular contractility and compliance in chronic volume overload. Left ventricular volume overload (LVVO) has been created in 18 dogs by anastomosing a Dacron conduit between the infrarenal abdominal aorta and inferior vena cava. The dogs previously were instrumented so that in the awake state LV pressure, systemic arterial pressure, LV dP/dt, myocardial segment length and excursion, and coronary and renal artery velocities could be monitored. The animals were stressed with separate infusions of alpha-adrenergic and beta-adrenergic agonists. Both at rest and with stress, over a 12-wk period, preejection, ejection, and contractility indices decreased. Left ventricular compliance decreased as exemplified by the increased ratio of end-diastolic pressure to end-diastolic length. The shunt was ablated in 7 dogs, and monitoring in conjuction with alpha- and beta-adrenergic stress foan additional 12 wk demonstrated an initial improvement in the previous indices. However, the amelioration plateaued and values similar to the control state were not attained. This suggests that potentially permanent alterations in ventricular function and compliance have occurred.


Metabolism of totally ischemic excised dog heart. I. Construction of a computer model. Construction and fit to the experimental data of a computer model of glycolysis, the Krebs cycle, and related metabolism in an ischemic dog heart preparation, involving 122 metabolites, 65 enzymes, and 406 chemical reactions, is described. The experimental preparation simulated is a dog heart excised from the body, placed in a beaker of Tyrode's solution, and sampled for 100 min; the model required only moderate modification from models representing perfused rat hearts, and little modification from a model of another ischemic dog heart preparation. Common underlying mechanisms for the ischemia are indicated, although this preparation appears to evolve more slowly with time, perhpas owing to heavy sedation and diffusion-limited transport. Lactate is, at first, exported and then accumulates intracellularly; pH falls, but not as much in the mitochondria as the cytoplasm; redox couples go reduced, but with counterintuitive time courses; calcium phosphate is calculated to precipitate, as often observed in cardiac ischemia.


Treatment of tardive dyskinesia with lecithin. Six patients with moderate or severe tardive dyskinesia participated in a 14-day double-blind crossover comparison of placebo with 50 g/day of lecithin. There were no side effects, and Abnormal Involuntary Movement Scale (AIMS) ratings of videotaped examinations indicated significant improvement in the dyskinesias of all subjects during the lecithin trial, even with concomitant administration of a constant dose of neuroleptic medication to five patients.


[Progress of technical medicine within the field of gerontoneurology (author's transl)]. 1938 respectively 1978 are dates for progress of technical medicine concerning gerontoneurology. Following the discussion of the development in technical (apparatus), chemical and immunological diagnostic activities in neurology the applicability in elderly people should be described. On principle there are no methods of investigations which cannot be used in geriatric causes. Main point of interest is the correct indication. Non invasive methods can be used without somatic risk; one has to observe only the fact of psychological stress for the patient; indications of invasive methods (merely angiography of vessels within the brain) must be focused on special diagnosis of the illness. Suspicious facts of space occupying intracranial process almost everytime ask for angiography following EEG and cranial computertomography. In cases of arteriosclerosis in aged people with typical changes within the vessel system of the brain one should only use angiographical investigations if clinical findings (based on noninvasive methods) show indications for surgical treatment in extracranial regions of the brain vessels. It might be the same procedure if shunt-operation between carotis externa and interna circulation system can be expected as curative or prophylactic influence within the neurological condition. In these cases risk of selective angiography of the vessels within the brain (outgoing from arteria femoralis) are much less dangerous than in direct charges. First of all neurological status, general condition and age will be decive for medical indication. One should not use the full range of diagnostic features in gerontoneurology only to satisfy diagnostic appeasement.


[Echocardiography in the elderly (author's transl)]. We report on questions and echocardiographic diagnoses in older patients and put out special views: value of ECG in coronary heart disease and in diagnosis of cardiomyopathy, for differentiation of systolic murmurs in the aged and detection of dilatation and atrial thrombosis.


[Model project: "Haus Lotharstrasse--residential and communication centre for seniors" (author's transl)]. "Haus Lotharstrasse, Wohn- und Begegnungszentrum für ältere Bürger" ("House Lotharstrasse, Residential and Communication Centre for Seniors") in Bonn had been established as a model institution of "open assistance for seniors". -The combination of 50 "protected appartments" (single and double appartments), a communication centre, accessible also for non-residents and service stations for "mobiles services" as Meals on Wheels, ambulant home-services (social service station), transport services for various purposes and consultation in individual social problems, proved to be extremely helpful in practice. Freedom and independence, combined with all necessary assistance and services when needed, promote new self-confidence and rehabilitation.


[Institutional and personnel obstacles to the realisation of co-determination by old-age home inhabitants (author's transl)]. Following the intentions of the "Heimgesetz" partizipation of the residents does not only concern a better protection of their interests, but also a change in the traditional, hierachical structure of organization of the homes for the aged. A realization of this aim is not only faced by the position of power of the management. On the one hand the law itself restricts the nature and the range of the partizipation of the residents concerning decisionmaking in the institution. On the other hand the residents' committee got too little power to carry through the interests of the residents against the interests of the institution. So a considerable change in the traditional structure of the organisation is not very likely.


[Therapy groups with patients and nursing staff in a geriatric hospital (author's transl)]. Within a very short time the non-demented, chronically hospitalized old person turns into a hospital-activity-oriented patient. He thereby gives up a considerablle part of his personality. In order to understand this process, special attention has to be paid to the intertwining of the dynamics of the chronic geriatric patient with the dynamics of the nursing staff. As a therapy experiment we have been conducting parallel talk-groups with patients and with their nursing staff for one year. As a result, the patients showed increased activity, increased dynamism, improved contact ability, increased interest in the outside world, and improved affect. The nursing staff also reported improvement of the group-patients' condition on the floor. With the  nursing staff we found a reduction of the defensive mechanisms, a separation from old nursing-role definitions, acceptance and encouragement of the patients in their new role, and improved satisfaction with patient contact. On the other hand, the nursing staff expects more personal contact to come from the patients. The groups have shown to be useful and have to a large extent reached the therapy goals.


Crystalloids of actin-like filaments in the Sertoli cell of the swine testis. Normal swine testes, congenital cryptorchid swine testes, and normal human tests were exposed to HMM (heavy meromyosin) after either glycerination or saponin treatment in order to determine whether the fine filaments composing the crystalloids in the Sertoli cells of the cryptorchid swine testes bind HMM to form arrowhead complexes. Short bundles of microfilaments observed in the basal part of the Sertoli cells in both normal and cryptorchid testes also bind HMM. Similar bundles of HMM-bound filaments are observed in the vicinity of spermatocytes. The periodicity of the arrowhead complexes is about 35 nm, and all arrowheads on a given filament point in the same direction. In addition, the polarity of the HMM-bound filaments in a given crystalloid or bundle is uni-directional. A mechanism for the formation of the swine crystalloids has been strongly support this hypothesis. Fine filaments of Charcot-Boettcher's crystalloid in human Sertoli cells did not bind HMM. Therefore the fine filaments of the human crystalloid are not actin-like in nature.


Further studies on bovine serum amylase--the effect of gel buffer pH. This paper describes the effect of gel buffer pH on the resolution of bovine serum amylase (Amylase I) isozymes in starch gel and the consequences for the understanding of the genetics of this locus. The two main findings are: (1) the existence of a satellite isozyme E to isozyme C which at pH 7.3 has the same mobility as the B isozyme but which at pH 8.0 migrates slower than B, and (2) the finding of three alleles Aml A, Aml B and Aml C in British cattle populations previously reported as having only Aml B and Aml C.


Sexual development and activity of men with disturbances of somatic development. By means of Questionnaires HTDM and SAM the heterosexual development and sexual activity were investigated in the following groups of males: 1. the control group consists of 345 married men from sterile marriages, who were adequately developed somatosexually, had normozoospermia in the ejaculate and a good potency; 2. in 48 unilateral and 57 bilateral adult cryptorchids; 3. in 101 married men with a distinct testicular hypoplasia, the long axis of both sexual glands being shorter than 30 mm; 4. in 110 patients with a Klinefelter's syndrome; 5. in 14 patients with hypogonadotropic hypogonadism. Whereas the retardation of heterosexual development was found only in two groups (group 4 and 5), a distinctly lowered activity in sex life was ascertained in all four pathological samples.


[Histological and ultrastructural study of intestinal ganglioneuromatosis. The multiple endocrine neoplasms type IIb syndrome]. The syndrome known as the Multiple Endocrine Neoplasia type III or type IIb presents a particular histological intestinal lesion: hyperplasia of the myenteric plexus. The electron microscopic study of the plexus of Auerbach in our observation suggests a disequilibrium of the different types of individual axonal sheaths compared to the descriptions of a normal plexus. The possible role of this anomaly in the genesis of intestinal manifestations in this syndrome is here discussed.


[The Cerebral Function Monitor. Description, functioning and interpretation principles]. The Monitor of Cerebral Function enables continuous monitoring of the cerebral electrical activity and this over long periods due to the slow recording speeds. The cerebral electrical signals picked up by the electrodes attached to the scalp are registered in the form of a curve which fluctuates to a greater or lesser extent depending on the recording speed. The examination of the height of the curve with respect to zero and its amplitude indicates the voltage of the cerebral activity and yields information regarding polymorphism. It is thus possible to monitor variations in cerebral activity over a prolonged period during anaesthesia as well as during the revival phase with the Monitor of Cerebral Function, the electroencephalogram being reserved as an aid to precise diagnosis and for localization and close scruting of the anomalies.


EEG processing by the Cerebral Function Monitor (CFM). The Cerebral Function Monitor (CFM) is a machine designed to monitor EEG over long periods of time from hours to several days. It produces on a slow speed chart recorder a write-out of a processed EEG signal in parallel with a continuous measurement of electrode impedance. A description is given of the way in which the CFM processes both EEG and electrode impedance information. Some CFM applications are mentioned.


[Cerebral Function Monitor (CFM) and electroencephalography (EEG). Experimental study]. This work is an attempt to connect the electro-encephalogram (EEG) and monitor of cerebral function (MCF) recordings during the experimental stimulation of the rabbit brain whether this is in the from of direct central stimulation, by stereotaxic location, or in the form of indirect stimulation via a peripheral nerve. These stimulations, performed under alfadione anaesthesia or under the neuroleptanalgesic sedative effect of chlorprothixine, are compared for every animal with the results of the control stimulations. The cardiovascular responses are recorded simultaneously. It has been found that, in simple narcosis induced by alfadione, there is much variation in the EEG recording and even more so in the MCF recording according to the quantity used and the block of responses to stimuli does not appear until there is deep anaesthesia. However, when chlorprothixine is used, the MCF trace is found to be very closely related to the trace of mild anaesthesia with accompanying block to all of the nociceptive stimulations. It would seem, therefore, if we accept the concept of levels of cerebral activity, that the use of the MCF could well open the way to a better understanding of the pure narcotic phenomena and of the neurovegetative response block to aggression.


[Use of the Cerebral Function Monitor in general anesthesia]. The Monitor of Cerebral Function was used in clinical anaesthesia for a wide range of procedures: both with and without inhalation anaesthesia, (halothane and enflurane); -intravenous anaesthesia, barbiturate or neuroleptanalgesia; -regional intravenous anaesthesia. The examination of the traces shows the importance of this type of monitoring of the action of drugs with their associated characteristics. The role of warning of possible overdoses or of the fore-runner signs of respiratory distress make the M.C.F. of clinical interest.


[Cerebral Function Monitor and anesthesia]. The Monitor of Cerebral Function was employed in anaesthesia for a double purpose: as a monitor of anaesthesia, of possible complications and of overdosage that might lead to cerebral damage; a bringing up to date of the comparative data on the various anaesthetic protocols. In this manner, we were able to demonstrate the during anaesthesia application of a cerebral monitor that is well designed and easy to handle. A comparative study of hypnotic anaesthetics and those that induce neuroleptanalgesia demonstrated that, in certain cases, the same anaesthetic stability is achieved when there is an early appearance of the electric silences as when the cerebral electrical activity is only slightly modified.


[Cerebral Function Monitor and responses to stimuli]. Sudden changes in cerebral activity occurring in response to controlled stimuli or resulting from surgery were recorded with the Monitor of Cerebral Function in an appreciable number of cases. The fluctuations in activity that were observed lasted for various lengths of time and consisted mainly of an elevation of the trace associated with cortical excitation. These fluctuations occurred in various different clinical situations such as under general anaesthesia or under er the effect of barbiturate poisoning. Once we eliminate the possibility that the fluctuations are simply recording artiefacts, then it would seem that their order of magnitude reflects the intensity of the somato-sensory cortical responses that are evoked by a nociceptive stimulus. If this is confirmed, then the M.C.F. would be capable of furnishing a great deal of new knowledge regarding the state of "reactivity" of the cerebral cortex, which is quite distinct from the monitoring of the depressive cortical state.


[Use of the Cerebral Function Monitor in cardiac surgery]. Having employed routinely the monitor of cerebral function in cardiac surgery operations for about a year, the authors now present an analysis of the variations in the traces of a group of 57 patients. They have found, when there is no major haemodynamic consequence associated with the induction of anaesthesia, and when there are no difficulties of a surgical or a technical nature accompanying the artificial extra-corporeal circulation, that the monitor curve stays perfectly stable. On the other hand, all sudden haemodynamic changes result in hypotension (haemorrhage, dysrhythmia, and a fall in flow in the extracorporeal circulation) that is reflected in the level of the monitor curve which also falls. They conclude, using examples of certain variations, that the monitor curve is a supplementary form of surveillance and that the trace recorded simultaneously with the anaesthetic sheet allows retrospective analysis of the haemodynamic events to be performed for each operation.


[Our experience using the Cerebral Function Monitor in anesthesia for heart surgery under extracorporeal circulation]. In our experience, although still fairly limited, of the monitor of cerebral function in cardiac surgery anaesthesia, we have found that this apparatus allows for a more precise supervision of cerebral activity during an operation with artificial extra-corporeal circulation. Due to a far simpler handling than for the classical electroencephalogram it should enable us to detect earlier states of cerebral damage during the course of the anaesthesia or the use of the artificial circulation. We also believe that it may have a valuable part to play in certain particular situations, as for example when dealing with an aortic dissecting aneurysm, or when there is an urgent need to perfuse the carotids.


[Clinical test of the Cerebral Function Monitor in intensive care]. Due to its simplicity, and because of the lack of an instrument designed for the routine monitoring of cerebral function in intensive care, the M.C.F. was used on patients presenting with disorders of consciousness resulting from various causes, including: exogenous poisoning; cranial trauma; cerebral anoxia. 15 examples are thus presented to illustrate the different clinical states. This apparatus revealed itself to be of particular use in the instantaneous evaluation of a patient's overall cerebral activity, as well as in the assessment of the patient's clinical prognosis. The slow speed of the trace enabled us to make continual recordings lasting several weeks. It was thus possible to compare immediately the levels of the disease. Furthermore, all variations--even of a transitory nature--of the level and fluctuations of this activity could be detected at all times. The M.C.F., therefore, would seem to be a very useful aid--perhaps indispensable--as a monitor of the comatose patient in an Intensive Care Unit.


[The Cerebral Function Monitor in intensive care]. The Monitor of Cerebral Function, the first apparatus designed for continual cerebral monitoring for prolonged periods, is used frequently as an aid during revival. Due to its ease of operation and its straight-forward displaying of the data, it can supply continual information on the state of cerebral activity. Wem used it in various situations where there was a risk of cerebral circulatory insufficiency. Besides this role in the prevention of emergency, we used the M.C.F. as a diagnostic tool in the assessment of brain death. An early confirmation of the presence of stage IV allows of a more efficient removal and grafting of the kidneys. Finally, we also use the M.C.F. in the study of abnormalities of behaviour in patients whose revival to consciousness is slow.


Removal of EKG from fetal CFM recordings. The monitoring of fetal EEG during labour can assist in identifying the effects on the fetus of anaesthetic and other drugs administered to the mother. Additionally it assists in detecting inadequate cerebral perfusion. One unsuccessful and one successful method are described of removing fetal EKG from the fetal EEG signal, so enabling the Cerebral Function Monitor to be used to monitor the fetal EEG. Examples of results are given.


[Use of the Cerebral Function Monitor in the study of physiological sleep]. After a brief description of the different phases of physiological sleep, the reasons for employing a new appatus, the Monitor of Cerebral Function, are discussed. This instrument, the first designed for continual monitoring of cerebral activity may be employed in neurophysiology. The results obtained are presented, i.e. the demonstration of a perfect correlation between the Monitor of Cerebral Function recording and the polygraphic methods. The paradoxal and rapid phases of sleep are easily distinguished. The study of paradoxal sleep, both in physiology and in pharmacology, could profit greatly from the use of the MCF due to the great advantage of its ease of operation.


Development of the CFM: the Cerebral Function Analysing Monitor (CFAM). Use of the Cerebral Function Monitor (CFM) to monitor anaesthetic procedures has led to improvements of design. A standard CFM can be modified to enable it to be controlled by a microprocessor. An altered chart output format is produced which incorporates both frequency information and a better indication of trends. Alpha-numerical information can be given on a visual display unit. The extended instrument, of which preliminary details are given, is called the Cerebral Function Analysing Monitor (CFAM).


[Critical analysis and future development of the Cerebral Function Monitor]. At London Hospital, a number of technical failings of the apparatus and certain difficulties in the reading of the trace came to light following prolonged and frequent use of the Monitor of Cerebral Function in varied clinical situations. We consider it appropriate to propose certain possible improvements of the existing M.C.F. in view of the advantage of its easy use. These ideas on the further development of the M.C.F. have centered on making better use of the output signal, and also on the addition of an instrument which would yield qualitative information on cerebral activity (frequency spectrum). These improvements, then, including the incorporation of a microprocessor that would render the apparatus more informative, and a better presentation of the data (e.g. alpha numbering on paper and on T.V. monitor), should help create a machine that is at once more sensitive and more practical without interfering with the advantages of ease of operation and of interpretation.


[The neuroendocrine response to Alfatesine or Ethrane anesthesia in humans]. The description of neuro-endocrine effects due to surgical stress and certain anaesthetic products led the authors to look for the action of alfadione and enflurane on the hypothalamic-hypophyseal-thyroidian-adrenal axis. Taking 20 subjects who were divided into three groups of 10, the authors measured the plasma levels of T3, T4, TSH, cortisol and ACTH during anaesthesia with alfadione (without surgery). This was group I. Group II were patients during surgery under alfadione. Group III was during surgery under enflurane. The results show the absence of significant changes in the plasma levels of the hormones measured. The authors conclude that alfadione changes the levels of T3, T4, TSH and cortisol even less than does enflurane, whether the anaesthesia is isolated or in a patient undergoing surgery.


[Comparative study of the neuromuscular effects of 3 curare-like agents in children]. The authors studied the effect of three curare-like agents in 92 children anesthetised with halothane (1 to 2 p. 100). The method used was to give increasing doses of d-tubocurarine, metocurine and pancuronium bromide by injection until a block of approximately 95 p. 100 of the contraction of the thumb was obtained. This was checked by electrostimulation. Each of the three groups of children who were treated with one of the three curare-like agents were subdivided according to age and dose-response curves were obtained. The time required to recover 10 and 25 p. 100 of a control contraction was also studied. The authors conclude that from the point-of-view of activity, metocurine and pancuronium are respectively twice and five times more powerful than d-tubocurarine. The recovery time for pancuronium is twice as short as that for metocurine and d-tubocurarine. Furthermore, even though they are more resistant than adults, children recover more quickly than them. There is no difference in sensitivity in children that could be related to age, and this was so in the three curare-like agents studied. However, individual differences were more marked in neo-natal infants of less than 10 days than in other groups.


[Role of the anesthetic consultation in an organization model of the anesthesia-resuscitation department]. The anaesthetic consultation is essential to give patients a sense of security. It should be organised taking into account the needs and resources of the department. In the light of the experience of the authors in an anti-cancer center, three main principles can be enumerated for this to be properly organised: the detachment of doctors from the surgical departments, a rotation in the department and a timetable for the consultations. The part played by the departments requesting help and the different secretarial offices is important. In this way one can anticipate and eliminate the improvisation which always occurs, to the detriment of the patient. Collaboration between the different departments involved is naturally indispensable. These general principles have beeen stated for at least a dozen or so years by a certain number of anaesthetists. It was quite easy to stranspose these principles and to adapt them to the organisation of the anti-cancer struggle. Such applications should be generalised.


[Trials of propanidid in anesthesia for bronchial endoscopy in infants and children]. This study reports a series of 48 bronchial endoscopies performed in children aged between 3 months and 16 years using Propanidide as sole anaesthetic agent. Individual variations were large. Repeated examinations showed that this type of anaesthetic had only moderate effects upon haemodynamic parameters. Disturbances in pH and PCO2 in arterial blood measured five, fifteen, twenty five and thirty five minutes after induction were less than with anaesthesia by inhalation of halothane. The quality of recovery of such that examinations could be performed on an ambulatory basis. Intravenous administration has the advantage of separating the anaesthetic from the endobronchial examination.


[Postoperative analgesia by constant flow injection of lignocaine in obstetrical and gynecologic surgery]. 154 surgical patients were given post-operative analgesia by peridural injection at a constant flow in the post-operative period after obstetric or gynecological surgery. These patients received 536.2 +/- 105.3 mu mol.h-1 (145.2 +/- 28.5 mg.h-1) of lignocaine for 46.97 +/- 15.56 h through a catheter omserted between L1-L2. The drug was given in concentrations which varied between: 27.7 to 18.5 m mol.l-1 (0.75 to 0.50 p. 100) depending on the age; and the volume varied between 17.5 to 30 ml.h-1 depending on the height. Satisfactory analgesia in 87 p. 100 of cases allowed all supplementary analgesia to be stopped. The only significant hemodynamic effect was a slight tachycardia (+ 15 p. 100). Two undesirable side effects were noted: a transitory but well-defined (type 2 or 3) motor paralysis, and an accumulation of plasma lignocaine (40 mu mol.l-1 (1.1 microgram.ml-1) at 48 h).


[Cardiovascular effects of a single injection of fentanyl in dogs under acute experimental conditions]. Experimental studies carried out in unselected dogs often face the problem of instabilit of various parameters both in terms of haemodynamics as well as acid-base balance. It is possible, with the injection of a single dose of Fentanyl of 0.35 mg.kg-1 given over a period of ten minutes to obtain, from the 30th minute after the injection, satisfactory cardiovascular stability (confirmed during 120 minutes in 9 dogs and 360 minutes in 2 of them). This haemodynamic state at T + 30 is obtained with a fall in mean blood pressure of -40 per cent, and an increase in peripheral resistance of +38 per cent and stroke volume of +11 per cent. This stability, obtained at the price of a stable normacapnia, correction of any possible metabolic acidosis and maintenance of body temperature, makes it possible to study the cardiovascular effects of certain types of treatment or of induced pathology.


[Prevention and treatment of urinary infection in patients with an indwelling catheter: continuous vesical irrigation with a mixed antibiotic solution of neomycin and polymyxin B]. A method of continuous lavage of the bladder using a solution containing a mixture of Neomycine and Polymyxine-B was tried out in 32 patients with indwelling urinary catheters. To do this, a three-channel catheter was used, lubricated with an antibacterial cream and connected to a plastic container which could be emptied without removing the catheter. This method of treatment, which was effective, well tolerated and simple to use, would appear to be a useful addition to the prevention and treatment of urinary infections in patients with in-dwelling catheters.


[Comparative study of postoperative nitrogen balance as a function of carbohydrate intake]. Postoperative nitrogen intake, which limits nitrogen catabolism and improves conditions of healing, classically implies a high calorie intake. The risks and dangers of hypertonic or hypersmotic solutions are such that the provision of nitrogen postoperatively in ordinary surgery is often avoided. The authors studied postoperative nitrogen balance for a given nitrogen intake with different calorie levels in a series of 50 patients undergoing digestive surgery. A first group (28 patients--mean age 54.6 years, mean weight 63.3 kg) received 12.4 g of nitrogen and 1000 calories per day. The second group (22 patients--mean age 52.5 years, mean weight 64.7 kg) received 12.4 g of nitrogen and 2200 calories. Daily nitrogen balance was calculated using the method of approximation described by Apfelbaum on the basis of urinary urea excretion. Statistical study of nitrogen balances for the first four days showed no statistically significant difference between the mean values in the two groups. For group A, the cumulative balance for the first four days was 7.60 g +/- 4.75 g, and for group B 7.85 G +/- 6.64 g. Limitation of postoperative nitrogen catabolism does not necessarily impose the need for high calorie intake, implying the use of a central venous catheter and administration at constant flow. The patient undergoing ordinary digestive surgery may benefit from postoperative nitrogen supplies, associated with a moderate calorie intake and administered via usual venous routes.


Effect of socio-environmental isolation on brain biochemistry, behaviour and psychoactive drug activity. Isolation has been widely described to induce a strong aggressive behaviour in many animal species and especially in rodents. A deeper analysis of this altered behaviour induced by isolation, allows for the identification of several other changes involving numerous peripheral, behavioural and neurochemical functions. As a consequence of the manifold aspects involved in this experimental situation, the definition "isolation syndrome" seems to be much more adequate than the simplest definition of "aggressiveness by isolation". On this framework, some similarities with psychoneurosis in men are also suggested.


Biochemical and behavioural studies on the interference between catecholaminergic and serotonergic central systems. L-DOPA, apomorphine and amphetamine increase emotional reactivity and aggressiveness, and/or evoke spontaneous attack behaviour in male rats. At the same time these compounds accelerate the turnover of endogenous serotonin (5-HT), increasing the brain concentration of 5-HIAA. L-DOPA, amphetamine and apomorphine antagonize the depressive effects of 6-tryptophan on behaviour. After the injection of L-tryptophan these dopaminomimetics facilitate the turnover of 5-HT in the brain. On the other hand, the tranquillizing effect of L-tryptophan correlates not only to the increased level of 5-HT but also to an accelerated catabolism of dopamine. After the simultaneous injection of L-DOPA and L-tryptophan, cross-influence on the turnover of 5-HT and dopamine is noted, while in behaviour the effects of L-DOPA prevail over those of L-tryptophan. PCPA blocks the behavioural effects of dopaminomimetics.


Effects of some adrenergic blockers on the abstinence syndrome of addicts to drugs and alcohol. Pyrroxand and butyroxan -- original drugs possessing hyghly selective alpha-adreno-blocking action at peripheral and central level-relieve symptoms of abstinence syndrome caused by narcotics and other addicting drugs. On the basis of these data it is suggested that adrenergic structures of the brain play a key role in eliciting the abstinence syndrome.


Brain tyrosine hydroxylase: kinetic properties and regulation of the activity. Electrical stimulation of rat hypothalamic synaptosome suspensions produced activation of tyrosine hydroxylase due to increase of the affinity for tyrosine and 6,7-dimethyl-5,6,7,8-tetrahydropterine cofactor, decrease of the affinity for dopamine and enhancement of substrate inhibition. Cocaine (10(-7) - 10(-5) M) in vitro caused enzyme activation; when administered to animals systemically (0.5 mg/kg) the drug produced inhibition of hypothalamic tyrosine hydroxylase probably through a receptor-mediated feedback mechanism.


[Familial cryptorchism (author's transl)]. Cryptorchism is a frequent finding in children, but the presence of several cases in the same family has been rarely published. In this paper a series of twelve families with several cases in each one is reported. The histologic study of testicular biopsy in all cases has not been meaningful because of the various lesions observed. After reviewing medical literature the possibility of an ignored hereditary factor is considered.


The effect of neuroleptics on brain tyrosine hydroxylase. The effect of a number of neuroleptics and tricyclic antidepressants on the activity of rat hypothalamic tyrosine hydroxylase was studied utilizing a direct spectrophotometric method. All the neuroleptics (but not the antidepressants) were able to reverse the substrate inhibition of the enzyme occurring when the tyrosine concentration in the medium was increased. Haloperidol, haloanisone and fluphenazine were found to activate the enzyme at optimal tyrosine concentrations in contrast to other neuroleptics which reduced the enzyme activity. The systemic administration of fluphenazine and clozapine was followed by an increase in the activity of striatal and hypothalamic tyrosine hydroxylase. The same drugs failed to produce this effect when administered chronically for 8 days.


[A fulminating case of Takayasu's disease (author's transl)]. Takayasu's disease rarely presents as acute episodes of vascular thrombosis, and the authors describe such a case in order to emphasize this fact. A description is given of the various types of clinical picture seen in this disease, for which a final diagnosis can only be made by combining angiographic and histology findings.


[Acute toxoplasmosis with necrotizing vasculitis (author's transl)]. Acute toxoplasmosis was diagnosed in a Japanese woman aged 31 years after the discovery of a raised lysis titre and agglutinins resistant to 2-ME, as well as early increases in specific IgM followed later by increases in specific IgG. A high fever was present and signs of mainly distal polymyositis. The muscle lesion was confirmed by EMG examination. No increase in muscle enzyme levels was noted at any stage of the disease. Muscle biopsy demonstrated inflammatory lesions in interstitial tissue and perimysium, and, more particularly, segmental necrotizing arteritis in several arterioles. All the arteriolar lesions were at the same stage of development. After prednisolone (60 mg/day) had failed to produce improvement, spiramycin was given and caused apyrexia in 48 hours and definite disappearance of all muscle signs within several days. Recovery was complete and there was no return of symptoms 18 months later. The authors discuss the association of acute toxoplasmosis, polymyositis, and necrotizing vasculitis, and suggest a possible pathogenic role for the immune complexes deposited on the arterial walls.


The scrotal pouch operation for undescended testis. Patients who had undergone a total of 167 orchidopexies by the scrotal pouch technique were followed up for 1-3 years. The technique is described in detail. At follow-up 6 testes were found to have retracted out of the scrotum and these were successfully dealt with at a second operation. One testis was hypoplastic in the scrotal pouch and another infarcted in the groin after the first stage of a planned two-stage procedure. The remaining 159 tests were entirely satisfactory, giving an overall success rate of 95.2%. This technique compares favourably with other methods of orchidopexy, both in achieving a satisfactory anatomical position and in avoiding damage to the testis.


Biology of cultured nerve and muscle.

Biology of cultured nerve and muscle. Cells from the nervous system can be grown in culture and exhibit many of the biophysical, biochemical, and morphological properties found in vivo. They can be induced to differentiate in culture and perform some of the interactions that occur in the nervous system, including synaptogenesis. A number of important questions relating to nervous system development and function have been approached in culture in ways that cannot be done in vivo. The use of clonal cell lines should lead to rapid progress in the analysis of the nervous system at the chemical level.


Beta-1-3-glucanase and dimorphism in Paracoccidioides brasiliensis. Mycelial and yeast forms of P. brasiliensis were tested for several glucohydrolases. In addition to high levels of beta-glucanases, low amounts of alpha-glucanase, chitinase and maltase were found. Tests for invertase, amylase and lactase were negative. The levels of beta-1,3-glucanase were higher in the mycelial form. The shift to the mycelial phase correlated with an increase in the levels of beta-1,3-glucanase. The enzyme was present in the cytoplasm, cell wall and culture medium. The extracellular enzyme was purified 42 fold by ammonium sulphate precipitation and gel filtration. Maximal activity was obtained at 60 degrees C and pH of 5.0 (acetate buffer or pH 6.0 (phosphate buffer). Its Km was 0.205 mg/ml. The cell wall-bound enzyme showed a higher temperature optimum. Optimum pH and Km were also slightly different. Following treatment of the cell walls with chitinase, beta-1,3-glucanase was released into the medium.


Role of immune complexes in rheumatoid polyarteritis. Serial clinical and serological observations were made on a patient with necrotising polyarteritis associated with rheumatoid arthritis. Significant levels of circulating immune complexes, as determined by a C1q binding assay, were observed up to 2 years before the clinical manifestations of polyarteritis but rose abrumptly immediately before and concurrently with the onset of polyarteritis. Concomitant serial determinations of C3, latex fixation titres for anti-immunoglobulin, and patterns of fluorescence of antinuclear antibody afforded insight into the nature of these somplexes, as did clinical and serological response to glucocorticoid and cytotoxic therapy. Our data suggest that the antibody involved in the complex was of the IgG class and capable of complement fixation.


[Assessment of five laboratory tests for differential diagnosis in bacterial and viral meningoencephalitides]. The usefulness of five different laboratory tests for differential diagnosis in bacterial and viral meningoencephalitides was assessed. The clinical manifestations and cytochemical alterations of cerebrospinal fluid (CSF) were used as criteria for diagnostic selection. The causal agent was identified by means of CSF cultures in 47.8 per cent of bacterial meningoencephalitis cases; Gram stain was postive in CSF smear in 34.8 per cent and protein electrophoresis in CSF did not show significant differences when compared to cases of bacterial or viral etiology and the control group. PH and CSF lactate determinations allowed diagnosis of all cases of bacterial meningoencephalitis and was not modified in those cases where this disease was of a viral origin. We suggest to add these determinations to the initial cytochemical study of CSF in all cases where meningoencephalitis is suspected.


[Insufficiency of penis development (micropenis). Etiological data in a series of 25 cases]. The diagnosis of micropenis was made in 25 boys aged 1 month to 16 years. This abnormality was associated with hypothalamic-pituitary deficiency in 12 boys (hypogonadotrophic hypogonadism, hypopituitary growth failure, Prader-Willi syndrome), with testicular disorders in 5 boys (anorchia, testicular dysgenesis). In the other 8 the micropenis was an isolated finding but the testicular response to HCG and the LH response to LHRH was significantly reduced (p less than 0.005). The results suggest there may be isolated gonadotrophia deficiency. The variety of conditions that are responsible for micropenis suggest that testosterone deficiency is an important causative factor. HGH may also be important as the penis may be small in HGH deficiency and growth occurs with treatment.


Temporal variability of somatosensory, visual, and auditory evoked potentials in schizophrenia. Previous findings in chronic schizophrenics showed greater than normal somatosensory evoked potential (SEP) waveshape stability before 100-ms after stimulus and reduced stability after 100 ms. To confirm and extend these findings, EPs to left and right median nerve stimuli, visual pattern flashes (VEPs), and auditory clicks (AEPs) were recorded from 14 locations in 86 patients and 33 controls. Three sets of analyses compared different patient groups with age- and sex-matched controls. The results confirmed previous SEP findings in chronic schizophrenics; no other subject group displayed the combination of high early and low late SEP stability. The SEP results did not generalize to VEPs and AEPs. Lead location was important for group differences. In overt schizophrenics, late epoch stability was low in all EPs. The results suggest certain limitations to the hypothesis of an impaired subcortical filtering mechanism in chronic schizophrenics.


Extraction and partial purification of mouse uterine alkaline phosphatase. Alkaline phosphatase in uterine homogenates from day 7 pregnant mice was solubilized using 0.2% (v/v) Triton X-100 and extracted wtih 20% (v/v) n-butanol. The procedure, which resulted in 182-fold purification, included ammonium sulfate precipitation, DEAE-cellulose anion exchange chromatography and Sephadex G200 gel filtration. Solubilization with Triton X-100 was an important step in the procedure since extraction with n-butanol alone only partially solubilized the enzyme and gave low extraction yields, much of the enzyme activity remaining in association with negatively charged residues. However, butanol extraction of Triton X-100-treated homogenates gave high yields of enzyme and eliminated p-nitrophenyl phosphatases which displayed activity in the pH range 3.0--7.5, together with a large proportion of inactive protein. The activity of the purified enzyme preparations was electrophoretically  homogeneous on cellulose acetate membranes, suggesting that the alkaline phosphatase in the mouse uterus exists in a single isozymic form. Polyacrylamide-gel electrophoresis revealed that the purified preparations contained at least one protein as an impurity. Attempts to further purify the alkaline phosphatase by isoelectric focusing were unsuccessful since the enzyme was found to have an isoelectric point of about 5.0 and at this pH it was rapidly inactivated.


Isolation, characterization and the role of rabbit testicular arysulphatase A in fertilization. Arysulphatase A was purified from rabbit testis. The purification was accomplished by a four-step procedure involving (NH4)2SO4 fractionation, chromatography on DEAE-cellulose, SP(sulphopropyl)-Sephadex and affinity chromatography on concanavalin A-Sepharose. The specific activity of purified preparation was 135 mumol/min per mg of protein, which represented an increase of 900-fold above that of the crude homogenate. The purified enzyme (20-50 micrograms) was found to move electrophoretically as a single band on polyacrylamide gel at pH 7.2 and 8.4. The homogeneous enzyme was shown to be a glycoprotein with 0.8% (w/w) of N-acetylneuraminic acid and 20% neutral sugar. The treatment of purified enzyme with bacterial neuraminidase had no effect on enzyme activity or kinetic properties, but it changed the elution prolife of rabbit testis arylsulphatase A through DEAE-Sephadex. The purified enzyme was strongly inhibited by Cu2+, Fe3+ and Ag+. It hydrolysed several sulphate esters including cerebroside 3-sulphate, ascorbic acid 2-sulphate and steroid sulphates. Pure arysulphatase was effective in dispersing the cumulus cells of rabbit ova.


The mechanism of transmembrane delta muH+ generation in mitochondria by cytochrome c oxidase. In rat liver mitochondria treated with rotenone, N-ethylmaleimide or oligomycin the expected alkalinization caused by proton consumption for aerobic oxidation of ferrocyanide was delayed with respect to ferrocyanide oxidation, unless carbonyl cyanide p-trifluoromethoxyphenylhydrazone was present. 2. When valinomycin or valinomycin plus antimycin were also present, ferricyanide, produced by oxidation of ferrocyanide, was re-reduced by hydrogenated endogenous reductants. Under these circumstances the expected net proton consumption caused by ferrocyanide oxidation was preceded by transient acidification. It is shown that re-reduction of formed ferricyanide and proton release derive from rotenone- and antimycin-resistant oxidation of endogenous reductants through the proton-translocating segments of the respiratory chain on the substrate side of cytochrome c. The number of protons released per electron flowing to ferricyanide varied, depending on the experimental conditions, from 3.6 to 1.5. 3. The antimycin-insensitive re-reduction of ferricyanide and proton release from mitochondria were strongly depressed by 2-n-heptyl-4-hydroxyquinoline N-oxide. This shows that the ferricyanide formed accepts electrons passing through the protonmotive segments of the respiratory chain at the level of cytochrome c and/or redox components of the cytochrome b-c1 complex situated on the oxygen side of the antimycin-inhibition site. Dibromothymoquinone depressed and duroquinol enhanced, in the presence of antimycin, the proton-release process induced by ferrocyanide respiration. Both quinones enhanced the rate of scalar proton production associated with ferrocyanide respiration, but lowered the number of protons released per electron flowing to the ferricyanide formed. 4. Net proton consumption caused by aerobic oxidation of exogenous ferrocytochrome c by antimycin-supplemented bovine heart mitochondria was preceded by scalar proton release, which was included in the stoicheiometry of 1 proton consumed per mol of ferrocytochrome c oxidized. This scalar proton production was associated with transition of cytochrome c from the reduced to the oxidized form and not to electron flow along cytochrome c oxidase. 5. It is concluded that cytochrome c oxidase only mediates vectorial electron flow from cytochrome c at the outer side to protons that enter the oxidase from the matrix side of the membrane. In addition to this consumption of protons the oxidase does not mediate vectorial proton translocation.


Limited-turnover studies on proton translocation in reconstituted cytochrome c oxidase-containing vesicles. We have investigated ferrocytochrome c-induced proton ejection from reconstituted cytochrome c oxidase-containing vesicles using careful control of the number of enzyme turnovers. Ferrocytochrome c caused the appearance of protons at the vesicle exterior, and this could be abolished by using a protonophore. In addition, its decay was dependent on the permeability of the vesicle membranes to protons and the number of turnovers of the oxidase. These observations indicate that the ejection of protons was the result of genuine translocation. The possibility of this translocation occurring via a Mitchellian loop as a result of the presence of a reduced hydrogen carrier contaminating the enzyme was considered and excluded. Proton-translocating activity in this reconstituted system depended critically on the ratio of enzyme to lipid used in the reconstitution process and we propose a rationale to account for this. We conclude that our data provide strong support for the proposal that cytochrome c oxidase acts as a proton pump and that approx. 0.9 H+ is excluded per ferrocytochrome c molecule oxidized.