Actions of iontophoretic phenytoin and medazepam on hippocampal neurons. In rats anesthetized with methoxyflurane, phenytoin (DPH) and medazepam (MDZ) were administered iontophoretically to pyramidal and granule cells discharging spontaneously or being driven by acetylcholine or glutamic acid. The objectives were to determine if: 1) these anticonvulsant agents exert direct effects on the rates of discharge of hippocampal neurons; 2) similarities exist between responses elicited by DPH and MDZ; and 3) pyramidal and granule cells differ in their responsiveness to the drugs. The firing rates of 38% of spontaneously active neurons were reduced by iontophoretic DPH. The incidence of depression by DPH depended upon the pretest discharge rates of the cells. Only 5% of cells with spontaneous rates less than 12/sec were depressed by DPH, but 80% with rates faster than 12/sec were inhibited. MDZ depressed 79% of spontaneously firing neurons regardless of pretest discharge rate. A majority of neurons whose firing rates were facilitated by either acetylcholine or glutamate were depressed by DPH or MDZ ejected iontophoretically. Pyramidal and granule cells responded similarly to putative transmitters, but differentially to the drugs. MDZ depressed a much greater proportion of spontaneously active granule cells then DPH. Phenytoin and MDZ differed with regard to the incidence of depression of spontaneous discharges, inhibition of slow firing cells, the proportion of granule cells depressed, and the duration of effect. These differences may be due to potency and pharmacokinetic factors or dissimilar mechanisms of action when the compounds are applied directly to single neurons.


Unusual alpha adrenergic receptor potency of methyldopa metabolites on melanocyte function. Catecholamines possessing alpha adrenergic receptor agonist properties induce lightening or reverse melanocyte stimulating hormone darkening of frog skin in vitro. The capacity to activate this alpha receptor by the methyldopa metabolites methyldopamine and methylnorepinephrine was compared with the capacity of the naturally occurring dopa metabolites, dopamine and norepinephrine. Melanocyte stimulating hormone-induced darkening or dispersion of the granules was reversed by each of these metabolites. Methylnorepinephrine was 10 times as potent as norepinephrine, and methyldopamine was 30- to 100-fold more potent than the naturally occurring dopamine. These inhibitory effects on melanocyte stimulating hormone could be blocked or partially impaired using the alpha adrenergic blocker, phentolamine. They were not affected by pretreatment of frogs with the monoamine oxidase inhibitor pheniprazine (Catron) nor by the application of pheniprazine, angiotensin or serotonin in vitro. This neuroendocrine model has alpha adrenergic receptor relationships analogous to those described in the central nervous system for methyldopa metabolites.


Alpha blocking action of the antihypertensive agent, prazosin. The vasodilatory and alpha adrenergic blocking properties of prazosin were studied in anesthetized rats and compared with the direct-acting vasodilator, diazoside. The hypotensive activity of diazoxide was unimpaired after ganglion blockade with pentolinium or alpha adrenoreceptor blockade with phentolamine; diazoxide also significantly attenuated angiotensin II pressor responses. In contrast, the  hypotensive action of prazosin was completely abolished, over a 10(4)-fold dose range, after ganglion or alpha adrenoreceptor blockade, and this agent failed, even in maximal hypotensive doses, to attenuate angiotensin II pressor responses. In addition, prazosin was shown to possess potent alpha adrenoreceptor blocking properties, significantly attenuating norepinephrine pressor responses and causing reversal of epinephrine pressor responses. These studies in the rat indicate that the hypotensive action of prazosin is not due to a direct relaxant effect upon vascular smooth muscle, but is attributable to alpha adrenoreceptor blockade.


Measurement of prostaglandin E2 in an inflammatory exudate: effects of nonsteroidal anti-inflammatory agents. A method was developed for extracting and measuring nanogram quantities of prostaglandin E2 (PGE2) from carrageenan-induced abscess in the rat. PGE2 concentration, quantitated by radioimmunoassay, was 42.5 and 92.9 ng/g of abscess in two studies. Anti-inflammatory activity, based on reduction in abscess weight, was observed with indomethacin, phenylbutazone, SC-19220 and A-22981; however, only indomethacin (10 mg/kg i.p.) significantly reduced PGE2 levels in the abscess tissue. Dose-related anti-inflammatory activity of indomethacin (1-10 mg/kg i.p.) was directly correlated with  reductions of PGE2 content in the abscess. These data support the theory that the anti-inflammatory activity of indomethacin in the carrageenan abscess model involves inhibition of prostaglandin formation. Dose-related suppression of abscess formation by SC-19220 (7.5-30 mg/kg i.p.) was not related to changes in PGE2 levels at the inflammatory site, which suggests that the anti-inflammatory mechanism of SC-19220 is not mediated via inhibition of prostaglandin synthesis.


The concentration of ionized magnesium in barnacle muscle fibres. 1. The total Mg in isolated fibres of Balanus aquila was 10-5 m-mole/kg wet wt. 2. The intracellular free Mg was measured by a null point method using Eriochrome Blue as an indicator of free Mg, and internal dialysis with solutions of varying ionized Mg concentrations. The results indicated a free Mg of 6 mM or 4-2 m-mole/kg wet wt. in the intracellular water immediately surrounding the dialysis capillary. 3. The ATP concentration was estimated to be 4-9 m-mole/kg wet wt. 4. A tentative partitioning of Mg among various intracellular constitutents based on present data combined with published work by others is (m-mole/kg wet wt): free, 4-2; MgATP, 4-2; myofibrillar bound, 1; residual (presumably bound to arginine phosphate and phosphate) ca. 1.


Separative pathways for urea and water, and for chloride in chicken erythrocytes. 1. Urea and water permeabilities of chicken erythrocytes are considerably lower than those of mammalian red cells. 2. The permeabilities to urea, thiourea and to N-methylurea (about 10(-6) cm/sec at 25 degrees C) were independent of concentration within a very broad range, and we found no evidence of interaction between transport of analogue molecules. The activation energies were between 17 and 19 kcal/mole, and urea transport was not inhibited by phloretin, which inhibits urea transport in mammalian red cells. 3. The water permeability of chicken red cells (as measured by the diffusion of tritiated water) was 1-35 X 10(-3) cm/sec at 25 degrees C. The activation energy was 10 kcal/mole, and the water permeability was not affected by phloretin or parachloromercuribenzoate. 4. It is concluded that the urea and water permeabilities of the chicken erythrocyte membrane are similar to those of a non-porous bimolecular phospholipid membrane. 5. Like the red cells of other animal species the chicken red cell membrane contains an anion transport system, mediating a rapid exchange of chloride across the cell membranes. The pH dependence, temperature dependence, and sensitivity to inhibitors were similar to the properties of the anion transport system found in mammalian red cells. Our study shows, therefore, that the transport system offers a highly specific pathway to the exchange of anions, without presenting an inspecific leak to the permeation of water and urea.


Cell size, macromolecular composition, and O2 consumption during agitated cultivation of Naegleria gruberi. Cell size, macromolecular composition, carbohydrate utilization patterns, and O2 concentrations were measured throughout the growth stages of Naegleria gruberi in agitated culture in a complex medium. Biphasic logarithmic growth occurred during the intial 83 hr of growth and the mean generation time was 7.0 hr and 19 hr during initial and secondary log growth stages, respectively. The maximum yield was 5 X 10(6) amebae/ml. The pH rose rapidly (1 pH unit) during the secondary log growth phase (52-83 hr) and continued into the stationary growth phase (83-120 hr). Dry weight, total protein, carbohydrate, and RNA per ameba increased just before the secondary log growth phase. RNA increase 31% to 35% per ameba at the end of each phase of log growth. DNA increased approximately 2-fold throughout the different growth phases. Average cell size increased 90% during biphasic log growth then decreased during stationary phase. O2 tension decreased from 100% to 18% of saturation during the biphasic growth phase, then increased during stationary growth to near 100% saturation. Glucose and total carbohydrate assays showed little utilization of those substrates throughout the growth stages. Naegleria gruberi presumably has a predominantly aerobic metabolism, also its metabolism may change during the different growth phases.


Use of 1-anilino-8-naphthalene-sulfonate as a probe of gastric vesicle transport. The interaction of 1-anilino-8-naphthalene-sulfonate (ANS) with vesicles derived from hog fundic mucosa was studied in the presence of valinomycin and with the addition of ATP. Evidence was found for two classes of sites, those rapidly accessible to ANS with a KD of 7.5 micronM and those slowly accessible, but rapidly accessed in the presence of valinomycin with a KD of 2.5 micronM. ATP transiently increases the quantum yield of the latter ANS binding sites only in the presence of valinomycin, but does not alter the number of KD of those sites. The time course of this increase correlates with H+ uptake and Rb+ extrusion by those vesicles and H+ carries such as tetrachlorsalicylanilide or nigericin abolish the ATP response. With ATP addition in the presence of SC14N and valinomycin there is transient uptake of SCN-. It is concluded that ANS is acting as a probe of a structural change dependent on a potential and H+ gradient.


Cation transport by gastric H+:K+ ATPase. A vesicular microsomal fraction isolated from hog fundic mucosa demonstrates the capacity to take up equal amounts of RB+ and Cl-. The amount of the Rb+ uptake is sensitive to the extravesicular osmolarity, and rate of uptake is sensitive to temperature. 86Rb+ efflux is dependent upon the cation composition of the diluting solution. ATP, but not beta-gamma methylene ATP, induces a reversible efflux of 86Rb+ from loaded vesicles, and this is dependent upon a functional K+-ATPase. The ATP induced efflux is not affected by CCCP (carbonyl cyanide m-chlorophenylhydrazone) or TCS (tetrachlorosalicylanilide) nor by lipid soluble ions or valinomycin. Nigericin inhibits the efflux by 40%. Uptake of the lipid soluble ion 14C-SCN- has been demonstrated and is enhanced by ATP only in the presence of valinomycin. The results are consistent with a neutral or isopotential exchange of H+ for Rb+ mediated by K+-ATPase.


Characterization of bile acid binding to rat intestinal brush border membranes. Studies were performed to characterize the binding1 of bile acids to intestinal brush border membranes. Total 14C-taurodeoxycholate binding was: 1) similar for brush borders prepared from jejunum and ileum, 2) linear with respect to monomer concentration, 3) uninhibited by a structural analog, and 4) not depressed by boiling or trypsin. A linear relationship existed between binding and the number of hydrogen bonds formed by a bile acid and the slope of the line corresponded to delta deltaF of 300 cal/mol. The binding of bile acids to the 105,000 x g supernatant fraction of sonicated brush borders was similar to the binding of phospholipid liposomes using gel chromatography. These data suggest that: 1) the kinetics and characteristics of binding of bile acid to ileal brush borders do not reflect the kinetics and characteristics of active ileal transport previously obtained in whole tissue preparations, but instead reflect the kinetics and characteristics of passive jejunal transport; 2) a determinant of binding is hydrogen bonding with water; 3) isolated intact brush borders are relatively polar membranes; and 4) binding to solubilized brush borders may represent partitioning between the aqueous phase and membrane lipid.


Purple membrane vesicles: morphology and proton translocation. Purple membrane vesicles prepared by different techniques differ widely in their morphology and ability to establish a proton gradient in the light. The procedures used to prepare active vesicles do not completely dissociate the purple membrane and thus preserve a preferential orientation of the protein, while most of the lipid is exchanged for added lipid. Responses to illumination are largely determined by the size of the vesicles and the degree to which bacteriorhodopsin is preferentially oriented. Any attempt to compare the interaction of different lipids with bacteriorhodopsin by measuring the pH response must take these factors into account. With an improved technique we have obtained vesicles of rather uniform size and bacteriorhodopsin orientation, which accumulate protons with an initial rate of 160 ng H+ sec-1 mg-1 protein at light intensities of 10(6) erg cm-2 sec-1. The kinetics of the process are complex and at present insufficiently understood.


Effect of pH on hyperthermic cell survival. Chinese hamster ovary cells incubated with various concentrations of CO2, to obtain extracellular pH values in the range of 6.40-7.85, were heated at 45.5C for 5, 10, or 20 minutes. Thermal sensitivity increased sharply from pH 7.35 to 6.65 (i.e., survival decreased from 1 X 10(-2) to 3 X 10(-5) for 20 minutes of heating), but remained constant from pH 7.35 to 7.85. The enhanced thermal sensitivity at pH values below pth 7.35 suggested that tumors should be preferentially destroyed by heat relative to normal tissue, since reports indicated that tumors were more acidic than the surrounding normal tissue.


Aryl and heterocyclic diazo compounds as potential environmental electrophiles. 4-Aminoimidazole-5-carboxamide, a component of human urine derived from the de novo purine biosynthetic pathway, was evidenced to undergo in vivo diazotization in rats following its sequential administration with NaNO2. The diazotization product, 4-diazoimidazole-5-carboxamide, undergoes intramolecular cyclization to yield 2-azahypoxanthine, the urinary presence of which was confirmed mass spectrometrically. 4-Diazoimidazole-5-carboxamide demonstrated dose-related mutagenicity in Salmonella typhimurium TA 100 and represents a potent electrophilic reactant similar to the proposed ultimate carcinogenic forms of arylalkylnitrosamines and arylnitrosamides. It is suggested that aryl and heterocyclic diazo compounds, as a class, warrant further study as environmental electrophiles representing potential biological hazard.


Mosquito transmission of wild turkey malaria, Plasmodium hermani. Culex nigripalpus experimentally transmitted Plasmodium hermani, a plasmodium of wild turkeys (Meleagris gallopavo) in Florida. The mosquitoes were infected by feeding upon blood induced parasitemias in domestic turkey poults. The resulting sporozoites, transmitted by either mosquito bites or injection, produced malaria infections in domestic poults.


Nosocomial bacteremia. Potential for prevention of procedure-related cases. During a six-month period, 187 inpatients had bacteremia associated with community-acquired infection and 91 patients had bacteremia from a nosocomial infection. The most frequently identified sites of infection in both types of bacteremia were the respiratory and urinary tracts. Escherichia coli and Diplococcus pneumoniae were the organisms most frequently isolated from cultures of patients with community-acquired bacteremia, and E coli, Staphylococcus aureus, and Klebsiella were most frequently isolated from patients with nosocomial bacteremia. Bacteremic nosocomial infections were related to urinary catheters, respiratory and intravenous therapy, or hyperalimentation in 32 of the 91 cases. Even assuming the unproved hypotheses that rigid adherence to current guidelines would prevent all of these procedure-related cases, 59 cases of bacteremia would still have occurred. This emphasizes the need for further research into prevention of nosocomial infection.


Costs and outcomes for different primary care providers. This study examined the relationship between levels of medical training and direct costs for 1,700 episodes of acute illness treated in ambulatory-care clinics. Faculty, family practice residents, and physician assistants were included as the providers. Total cost and four component costs were examined. An outcome was defined as good if the patient returned to his usual level of functioning after an acute illness episode. Average total cost per episode was not related to type of provider, but there were significant (P less than .05) differences among providers in laboratory and medication costs. Faculty and physician assistants produced higher costs, especially for patients who experienced bad outcomes. Both costs and percentage of good outcomes achieved were similar in first-, second-, and third-year residents.


[In vitro examination on antibacterial activity of ciclacillin (ACPC) against clinically isolated strains (author's transl)]. (1) The antibacterial acivity of ciclacillin (ACPC) with inoculum size of 10(6) cells/ml was four times less potent than that of ampicillin (ABPC) and 4 approximately 8 times less potent than that of AMPC, but was 4 approximately 8 times more potent than that of CEX against Streptococcus pyogenes. For Streptococcus pneumoniae, ACPC was 2 approximately 4 times less active than ABPC and AMPC, but 16 approximately 32 times more active than CEX. Staphylococcus aureus was 4 approximately 8 times less susceptible to ACPC than to ABPC and AMPC, but 1 approximately 2 times more susceptible than to CEX. Against E. coli, ACPC was as active as CEX, 2 approximately 4 times less active than ABPC, and 4 approximately 8 times less active than AMPC. (2) It was suposed that ACPC was more resistant to penicillinase and more antibacterial with inoculum size of 10(6) cells/ml cells/ml than with 10(6) cells/ml. ACPC was 4 approximately 8 times less active than ABPC, and AMPC against Staphylococcus aureus with 10(8) cells/ml, while with 10(6) cells/ml, it was 2 times less active than ABPC and AMPC. (3) ACPC-resistant strains (greater than or equal to 3.13 microng/ml) of Streptococcus pyogenes and Streptococcus pneumoniae were not found. (4) A difference was noted in MIC of three semi-synthetic penicillins, ACPC, ABPC and AMPC, against Staphylococcus aureus, and E. coli between the sources from which their strains were isolated. (5) There were many strains resistant to erythromycin (EM) and josamycin (JM) (greater than 60%, respectively to both antibiotics) in Stretpococcus pyogenes and pus-isolated Staphylococcus aureus. No strains of Streptococcus pyogenes, were found resistant to EM and JM.


Effects of metiamide and propranolol on gastric secretion in anesthetized dogs. The effects of metiamide, a histamine H2-receptor antagonist, and propranolol, a beta-adrenergic blocking agent, on gastric secretion were studied in anesthetized dogs. Metiamide, 1.45 mg/kg i.v., markedly inhibited the gastric secretion induced by a continuous i.v. infusion of tetragastrin (8 microng/kg-hr), histamine dihydrochloride (160 microng/kg-hr), or methacholine bromide (100 microng/kg-hr). Propranolol 0.5 or 1.0 mg/kg i.v. produced a significant potentiation of tetragastrin-induced gastric secretion but no influence of the secretion induced by methacholine. Propranolol at 5 or 10 mg/kg i.v. produced a slight reduction of the tetragastrin-induced secretion and a significant reduction of methacholine-induced secretion. Histamine-induced gastric secretion was not affected by propranolol at either 1 and 10 mg/kg i.v. These findings lend support to the hypothesis that interactions among histamine, gastrin and acetylcholine receptors do occur though the degree would not be the same in all directions.


Descending release of acetylcholine from the locally distended guinea pig ileum. The effects of local distension of the intestinal wall on the release of acetylcholine (ACh) from the adjacent non-distended part were studied with the segment os isolated guinea pig ileum. Local distension of the intestinal wall induced the increased release of ACh in the distended part and in its anal side but not in its oral side. Such aboral release of ACh by local distension was abolished by tetrodotoxin or atropine in the concentrations which did not block the release in the distended part. When hexamethonium was applied exclusively to the distending part, significant increase of ACh release was observed in both the regions oral to and anal to the distended part. It is suggested that distension stimuli applied to the myenteric plexus are transmitted aborally along the network of the Auerbach's plexus to the anal direction. The release of ACh from the intestine by nicotine or DMPP differed from the occurring during local distension in that the release was localized to the part of the intestine to which the drug was applied.


Purification of histamine receptor. (IV) Specificity of binding of various drugs to the histamine receptor-rich fraction and to solubilized binding sites. Studies were made on tritiated histamine binding to the receptor-rich membrane fraction and solubilized sites and its displacement by various drugs. H1-Agonists and antagonists displaced histamine most effectively. A H2-agonist and atropine were less effective and propranolol, phentolamine and imidazole acetic acid had little effect. The solubilized binding sites showed the same specificity of binding as the membrane fraction. Membrane fragments had two binding constants, whereas solubilized sites had only one. Solubilized sites bound similar amounts of histamine and dibenamine: the latter was applied to intact tissue under conditions which would presumably cause specific binding to histamine receptors. These binding characteristics show that the method used was adequate for purification of histamine receptors from smooth muscle of cat small intestine.


[Acquired colour-vision-deficiencies caused by side-effects of pharmacotherapy (author's transl)]. Acquired colour-vision deficiencies are an early indicator for drug-induced retinopathy as well as drug-induced retrobulbar neuritis. Koellner's rule, which says, that damage of the retina induces a tritan-defect, and damage of the optic nerve induce a red-green-defect is also valid for defects secondary to drug-toxicity. Pseudoisochromatic plates, anomaloscope and other tests (Panel D-15-test) have to be selected correspondingly to use them as screening-methods.


beta-Adrenergic receptors in rat kidney: direct localization by a fluorescent beta-blocker. A new fluorescent beta-adrenergic blocker, 9-amino-acridin propranolol (9-AAP), was administered intravenously to albino rats. Fluorescent aggregates of 9-AAP binding sites were concentrated in the vascular poles of the glomeruli in association with the preglomerular afferent arterioles. 9-AAP fluorescence was reduced following pretreatment with (+/-)- and (-)-propranolol and was less affected in rats pretreated by the (+)-racemic isomer. 9-AAP binding sites were also observed on the lining epithelium of the renal collecting system. Our data suggest that 9-AAP may label beta-adrenergic receptors in rat kidney.


Ultrastructural localization of calcium in normal and abnormal skeletal muscle. Calcium was demonstrated ultrastructurally as a fine black reaction product with unbuffered 2% saturated potassium pyroantimonate, pH 9.4. In comparison with normal muscle, there was increased precipitate in degenerating skeletal muscle fibers and some degenerating-regenerating fibers occurring in pathologic human muscle, regardless of disease entity, and in experimentally injured rat muscle. The pathologically increased calcium was mainly within the sarcoplasmic reticulum and mitochondria. Both structures could be completely blackened. Nuclear calcium was also increased, the precipitates being localized as circular profiles within the nucleoli and heterochromatin as well as being associated with the nuclear envelope. Myofibrillar calcium was only modestly increased. When normal rat muscle was preincubated in 136 mM calcium-enhanced Hanks' medium, calcium accumulated in the muscle fibers--it was especially heavy in the mitochondria and sarcoplasmic reticulum and appeared identical with the pathologic human and rat muscle fibers. Preincubation of normal rat muscle in 0.1 M acetate buffer (pH 4.65) before calcium loading augmented myofibrillar staining, mainly in the H-zone of the A-bands excluding the M-zone and in broad irregular N1, N2, and "N3" lines of the I-bands. EMMA-4 electron probe microanalysis and EGTA (ethylene glycolbis (beta-aminoethyl ether)N,N'-tetraacetic acid) chelation prior to staining confirmed that the precipitate in the several loci was calcium antimonate. It is proposed that in skeletal muscle fibers injured by various pathologic processes, a breach of the plasmalemma barrier to calcium occurs as a very early abnormality. Extracellular calcium would then pour into the aqueous sarcoplasm of the muscle fiber, from which it would be withdrawn by and accumulated with the still active organelles normally having a great avidity for uptake of this ion, especially the mitochondria and sarcoplasmic reticulum. The resultant organellar calcification would impair function and damage the structure of proteins and phospholipids.


[Prolongated amnesia after "rohypnol" i.v. before local anesthesia and responsiveness during operation (author's transl)]. An up-to-eight-hour lasting anterograde amnesia is achieved by "Rohypnol" i.v. causing no excitation before local anesthesia is given (prolongation by analgetics, anesthetics, neuroleptics). The cardiovascular functions remain stable with spontaneous breathing and preservation of the swallow and coughing reflexes. During the operation the patient is responsive and cooperative. The patient answers all questions, moves his body into any wanted position and when ordered he performs Valsalva's manoeuver without any remembrane. If not spoken to and having no pain he falls asleep right away. Postoperative vomiting is reduced. The patient feels relaxed after waking up. No complications have been noticed during more than 500 operations. The later questioning of all patients showed only 4 patients (with unsufficient preoperative sedation) who could remember part of the terminal phase of the operation.


Effect of chlorhexidine on plaque development in an artificial mouth. The effect of chlorhexidine on the development of plaque, resulting from the inoculation with saliva of a tooth mounted in an artificial mouth, has been studied. The agent delayed the formation of plaque and also inhibited changes in pH and Eh, whether sucrose was present or not. Applied as a rinse at intervals of 12 h it prevented formation of plaque and pH and Eh remained constant. Moreover, chlorhexidine inhibited pH and Eh changes in established plaque. A single application of a gel containing chlorhexidine also greatly inhibited plaque development.


A microcalorimetric study of the growth of Klebsiella aerogenes in simple salts/glucose media. Heat output-time records or 'thermograms' produced during the aerobic growth of Klebsiella aerogenes in simple salts/glucose media with growth limiting glucose concentrations of 2.0, 1.0 and 0.5 g dm-3 were obtained using a flow-microcalorimeter fitted with an aerobic cell. These traces are interpreted in terms of the recorded oxygen tension, pH, glucose concentration and bacterial population of the culture. Heat output is greatest during the phase of exponential growth, indicating that here the organisms are most energetically inefficient. During the stationary phase aerobic processes, which give rise to a low oxygen tension, produce a smaller heat output until secondary metabolic processes are complete.


Studies of yeast alcohol dehydrogenase with 3-aminopyridine monucleotide. 3-Aminopyridine mononucleotide, a nicotinamide mononucleotide analog, was prepared by enzymatic cleavage of 3-aminopyridine adenine dinucleotide by a snake venom phosphodiesterase and isolated by means of ion exchange chromatography. The spectrophotometric and fluorometric properties of this analog were studied. Several anions were shown to quench the fluorescence intensity of this analog. pH was shown to have a pronounced effect on the fluorescence intensity. 3-Aminopyridine mononucleotide was shown to be a coenzyme-competitive inhibitor of yeast alcohol dehydrogenase. The 3-aminopyridine mononucleotide was diazotized with the use of nitrous acid. A time dependent irreversible inactivation of yeast alcohol dehydrogenase resulted from incubation with the diazotized 3-aminopyridine mononucleotide at pH 7.0. Incubation of the enzyme with NAD prior to the addition of the diazotized 3-aminopyridine mononucleotid protected the enzyme against inactivation.


[Vaccination complications after oral poliomyelitis vaccination (author's transl)]. A vaccination complication is only to be recognized if, taking into consideration the incubation time, the clinical picture coincides with that of spontaneous poliomyelitis. Apart from exceptional cases, virological studies are only of importance for the assessment if they are carried out in the acute or subacute stages. Only six out of more than 150 cases could be accepted as vaccination complications.


Chronic urticaria as a manifestation of necrotizing venulitis. In a group of patients with a syndrome consisting of recurrent episodes of urticaria, arthralgia, abdominal pain, and (rarely) glomerulonephritis, examination of skin biopsy specimens showed necrotizing venulitis. An elevated erythrocyte sedimentation rate was the most common laboratory abnormality. Analyses of serum immunoglobulins revealed random abnormalities of immunoglobulin levels, and assessment of the complement system showed two groups of patients--some with hypocomplementemia and others with a normal complement system. In those with hypocomplementemia, there were low levels of C1q, C4 and, occasionally, C3, compatible with activation of the classic complement pathway. Although the cause of this syndrome is unknown, the complement profiles suggest that more than one mechanism of vascular damage may be operative.


Isolation of Histoplasma capsulatum from soil in the Aguas Buenos Caves, Aguas Buenos, Puerto Rico. I. An ecological approach. Only one out of 19 soil sampling sites chosen for isolation of H. capsulatum studies yielded positive results. The stations were located in Cueva Oscura, which is part of the Aguas Buenas Caves system. The habitat characteristics of these station are believed to be responsible for the presence of the fungus.


X-ray study of the lithium complex of NAD. The Li+-NAD+ complex exists as a 'dimer' of two molecules arranged head-to-tail with Li+ coordinated tetrahedrally to adenine N(7) and three pyrophosphate oxygens. Adenine is stacked intermolecularly on nicotinamide. The conformation of NAD+ is 'extended' and similar to that found in holoenzyme complexes. This is in contrast to the 'folded' structure proposed from spectroscopic studies.


Effect of pyridoxine on the growth of Morris hepatoma No. 7288Ctc and enzyme activity. The effect(s) of lack of dietary pyridoxine (PX) on the growth of Morris hepatoma no. 7288Ctc was studied. Buffalo strain female rats were fed a diet lacking PX. Pair-fed controls were fed the same diet with PX added. Animals were inoculated with no. 7288Ctc hepatoma cells at 21 days and were sacrificed 16 days later. Host livers and tumors were removed, weights recorded and the activity of tyrosine aminotransferase (TAT; L-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) was determined in both host liver and hepatoma. The average weight of 30 hepatomas grown in pair-fed control rats was 11.61 +/- 1.5 g while the average weight of the same number of hepatomas grown in animals fed the PX free diet was 4.73 +/- 0.7 g (P less than 0.001). Further TAT specific activity levels were 39% and 32% higher in host livers and tumors from deficient animals, respectively. The results show that availability of dietary pyridoxine stimulates the growth of this hepatoma and, in addition, exercises a type of control over the expression of TAT activity.


Expression of hormonally induced tyrosine transaminase in normal, host liver and three Morris hepatomas. Cytoplasmic tyrosine transaminase (L-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) was partially purified from normal, host liver and three Morris hepatomas and subsequently resolved by electrophoresis on polyacrylamide gels. Enzyme activity was detected histochemically in situ on the gels. Seven enzymatically active forms were detected in normal liver. The presence of growing hepatomas altered significantly the expression of this enzyme. Only one, two and four activity peaks were detected in the host liver of animals with highly (most liver-like), well and poorly (least liver-like) differentiated hepatomas, respectively. Similarly, only one, four and six peaks were detected, respectively, in highly, well and poor differentiated hepatomas.


[Allogenic inhibition of the stem hematopoietic cells in the bone marrow of adult mice and in the embryonal liver]. The maternal effect was shown to influence the degree of allogenic inhibition of stem hemopoietic cells of the embryonic liver and adult bone marrow in CBA and C57Bl/6 mice. The display of allogenic inhibition of stem cells of the embryonic liver and adult bone marrow proved to be similar in C57Bl/6 mice and dissimilar in CBA.


[Effect of syngenic lymphocytes on allogenic inhibition of hematopoietic stem cells of embryonic liver]. The transplantation of liver from the embryos and newborn C57BL-6 mice to the lethally irradiated hybrids (CBA X C57BL/6) F1resulted in 90% allogenic inhibition of the colony-forming activity of the donor elements. The degree of allogenic inhibition of liver cells of 19 days old embryos and newborn mice may be changed with the help of syngenic lymphocytes of adult mice or delayed transplantation of cells 72 hrs following the irradiation of recipients but these procedures proved to be ineffective with the liver cells of 13 and 16 days old embryos. A suggestion is put forward to the effect that the allogenic inhibition is based on the active reaction of recipient hybrids (CBAXXC57BL/6) F1 to the stem hemopoietic cells of C57BL/6 mice.


[NAD+/NADH ratio in the mitochondria of the oocytes and ova of groundling, Misgurnus fossilis (L.)]. The ratio NAD+/NAD-H was detemined in mitochondria of the loach oocytes and eggs on the basis of concentrations of the glutamate dehydrogenase reaction intermediates. This ratio increases 6 times upon the oocyte maturation. The importance of this ratio in the metabolism of oocyte and embryo is discussed.


A comprehensive treatment approach to chronic low back pain. A comprehensive treatment program for chronic disability related to back disease has been presented. This program has used not only more traditional methods of medical care for the structural disabilities of chronic mechanical back disorders, but has used principles of active patient participation in the improvement process. The patients are educated in the manifestations of pain behavior in the phase II treatment program emphasis on pain sources is downgraded to allow positive reinforcement for healthy behavior to develop. By use of an organized team approach, a significant number of patients can be processed; and an overall reduction in use of alternative medical resources has occurred.


Effect of valine on propionate metabolism in control and hyperglycinemic fibroblasts and in rat liver. Measurement of methylmalonyl-CoA mutase and propionyl-CoA carboxylase activities in lysates from fibroblasts derived from control, nonketotic hyperglycinemia, propionic acidemia, and both vitamin B12-responsive and -nonresponsive variants of methylmalonic acidemia showed only one abnormality: a 59% decrease in carboxylase activity in the nonketotic hyperglycinemic lysates (P less than 0.01). When fibroblasts from all cell types were grown on valine-supplemented (24 mM) media, mutase activity was generally inhibited. As for carboxylase activity, control lines were inhibited 35% as compared to controls without valine and propionic acidemia activity was undetectable. On the other hand, carboxylase activity in both methylmalonic acidemia variants was increased 40% and nonketotic hyperglycinemia carboxylase activity was increased 80% (P less than 0.01) when grown on valine-supplemented media. Isoleucine could not substitute for valine in producing increased carboxylase activity in these mutants. Glycine cleavage activity in fresh rat liver homogenates (11.1 micronmol/gm protein/90 min) did not vary significantly when 24 mM valine was added to the reaction (9.9 micronmol/mg protein/90 min). Therefore, the hyperglycinemia observed in both ketotic and nonketotic forms is probably not caused by a direct effect of valine on the glycine cleavage reaction. These data suggest that the presence of increased amounts of propionic acid in serum or urine does not necessarily rule out the possibility of nonketotic hyperglycinemia due to the decreased activity of the carboxylase enzyme.


Otitis media in children less than 12 weeks of age. Cases of otitis media in infants under 12 weeks of age were reviewed to delineate the frequency, clinical features, and etiologic agents involved. Tympanocentesis was performed in 42 infants, 0 to 5 weeks of age, and in 17, from 6 to 11 weeks of age. The most common symptoms were irritability/lethargy (69%), fever (52%), cough (36%), vomiting (21%), diarrhea (20%), tachypnea (20%), and anorexia (18%). Associated illnesses were present in 33 (54%) of the patients, the most common being pneumonia (9), bronchiolitis (7), meningitis (6), conjunctivitis (4), and omphalitis (4). No peripartum infections or severe perinatal problems were found. Common respiratory pathogens were the predominant etiologic organisms, but coliform organisms were identified in 18% of the infants under 6 weeks of age. Cultures were sterile or grew organisms of questionable pathogenicity ("nonpathogens") in 39% of specimens. Since the signs and symptoms of otitis media in children less than 12 weeks of age are nonspecific and frequently associated with other major illnesses, the physician caring for these infants needs to be more aware of this disease and the therapeutic problems it presents.


[Diagnosis of hepatic metastasis by enzymatic assay. Value of gamma-glutamyltranspeptidase]. Variations in serum enzyme levels were studied in 50 patients suffering from various types of neoplasm, 25 of whom had hepatic metastases. In the absence of any associated hepato-biliary or pancreatic disorder, gamma-glutamyl-transpeptidase would appear to be a reliable test in 96 % of cases. It represents a factor of assessment which merits a place in the prognostic study of all types of neoplasia.


Aminoacylation of tRNA Trp from beef liver, yeast and E. coli by beef pancrease tryptophan-tRNA ligase. Stoichiometry of tRNATrp binding. The Michaelis constants and the maximum velocities in the aminoacylation reaction of tRNATrp from beef liver, yeast and E. coli by pure beef pancreas tryptophan-tRNA ligase show that this mammalian enzyme recognizes and charges the two eucaryotic tRNAs with the same efficiency. The rate of aminoacylation of the procaryotic tRNATrp by the enzyme is three orders of magnitude lower. The pH optimum of aminoacylation is 8 for both eucaryotic tRNAs. The optimum magnesium concentration is different. The rate is maximum when magnesium concentration is stoichiometric to ATP concentration for tRNATrp from beef liver and 10 mM above ATP concentration for tRNATrp from yeast. The number of binding sites on the enzyme for the two eucaryotic tRNAs has been measured by equilibrium filtration on Sephadex G-100 and found equal to two.


Equimolar addition of oligoribonucleotides with T4 RNA ligase. T4 induced RNA ligase will join equimolar concentrations of two oligoribonucleotides, (Ap)3C and p(Up) 5, to form a single product, (Ap)3Cp(Up) 5, in high yield. The presence of the 3' phosphate on p(Up)5 prevents the  oligomer from adding to itself. The pH optimum of the reaction is about 7.5, but less of the undesirable adenylated intermediate, App(Up) 5, forms at pH 8.2. The reaction rate is a linear function of oligomer concentration from 3 micronM to 0.6 mM. The data suggest that T4 RNA ligase will be a useful enzyme for the synthesis of oligomers of defined sequence.


Circular dichroism study of polyriboxanthylic acid. We report in the present paper the circular dichroism spectra of poly(X) at different pH and temperature values. The spectra are characteristic of three stable forms of poly(x) in the pH range of protonation of xanthosine. An electrostatic barrier is proposed to account for the hysteresis and metastability observed in a certain pH range. Some results on oligo(X) at basic pH are also presented. Poly(X) at basic pH is investigated also by hydrodynamic techniques.


Polyamine induced aggregation of DNA.

Polyamine induced aggregation of DNA. Polyamine induced aggregation of various DNAs has been studied under conditions usually employed in many enzymatic assays where DNA is one of the substrates. Spermine was by far the most efficient polyamine in causing aggregation followed by spermidine and cadaverine. All double-stranded and naturally occurring single-stranded DNAs were found to aggregate. No aggregation of single-stranded homodeoxypolymers could be detected under the same conditions. The concentration of polyamine at which the aggregation commenced was found to be a linear function of the DNA concentration. The slope of the curves depended on the nature of the polyamine, DNA the concentration of Mg++ and the ionic strength.


Glycosyl conformational and inductive effects on the acid catalysed hydrolysis of purine nucleosides. The log kobs vs. pH profiles were determined in the intermediate acidity region for the glycosyl hydrolysis of guanosine and its 8-amino, 8-monomethylamino, 8-dimethylamino and 8-bromo derivatives. The decreased rate of the 8-amino and enhanced rate of the 8-bromo compound compared to guanosine support an A type mechanism: base protonation followed by glycosyl bond cleavage. All three 8-amino guanosines exhibited log kobs - pH profiles clearly showing that both mono and di-base protonated nucleosides undergo hydrolysis. The 700 fold rate acceleration of 8-N(CH3)-guanosine compared to 8-NHCH3-guanosine and the 110 fold rate acceleration of 8-N(CH3)2-adenosine compared to 8-NHCH3-adenosine could be unequivocally attributed to the fixed syn glycosyl conformation of both 8-dimethylamino compounds and relief of steric compression upon hydrolysis in these molecules. The lack of anomerization of all substrates during the course of the reaction supports an A rather than a Schiff-base mechanism.


Isolation and characterization of N6-succinyladenosine from human urine. From the urines of colon carcinoma patients and normal  subjects we have isolated a nucleoside in which an amino group of aspartic acid is attached to the six position of purine ribonucleoside. The structure, N6-succinyladenosine, N-(9-B-D-ribofuranosylpurin-6-yl)aspartic acid was assigned on the basis of spectral data, chemical degradation, and by synthesis. The ultraviolet and mass spectra, chromatographic and electrophoretic mobilities, and the chemical properties of the naturally occurring nucleoside were identical to those of the synthetic N6-succinyladenosine. In contrast to the methylated and hypermodified nucleosides which are products of RNA catabolism, this urinary nucleoside appears to be derived from adenylosuccinic acid, a key intermediate required in the biosynthesis of ubiquitous, natural purine nucleotide adenosine-5'-monophosphate (AMP).


Polynucleotides. XLVI. 1 Synthesis and properties of poly (2'-amino-2'-deoxyadenylic acid). Poly (2'-amino-2'-deoxyadenylic acid)  [poly (Aa)] was prepared from chemically synthesized 2'-amino-2'-deoxy-ADP by the catalysis of polynucleotide phosphorylase. Poly (Aa) showed a similar UV absorption spectra to poly (A), but quite different CD spectra at pH 7.0 and 5.7. At the former pH it showed a single negative Cotton band and at the latter a curve with a large splitting of bands. Acid titration of poly (Aa) suggested protonated form below pH 7.0. Temperature absorption profiles and their dependency on sodium ion concentration suggested an ordered structure for poly (Aa) which is stabilized by stacking of bases and intrastrand interaction between 2'-amino and internucleotidic phosphate groups. Poly (Aa) forms a 1:2 complex with poly (U) at neutrality and its Tm was 45 degrees in the presence of 0.15M sodium ion.


The ANA and research in nursing.

The ANA and research in nursing. Research activities which always have been part of the American Nurses' Association program have increased greatly in the last 15 years. Among ANA's significant contributions to nursing research have been sponsoring nine nursing research conferences (1965-1973) and establishing the ANA Commission on Nursing Research and Council of Nurse Researchers.


[Study of the conditions maintaining the synthesis of alpha-amylase by Bacillus species]. The effect of temperature and different carbon sources on the growth of Bacillus species and the synthesis of alpha-amylase was studied. The temperature of 40 degrees proved to be optimal for those processes. Starch was found to be the best carbon source. The maximum accumulation of the enzyme was seen by the 40th hour of growth.


[Phospholipase of Bacillus cereus].

[Phospholipase of Bacillus cereus]. Phospholipase activity of 10 strains of Bacillus cereus was studied. The most active strain of Bac. cereus--phospholipase producer was selected. A cultivation mixture of Bac. cereus optimal for the phospholipase synthesis was found to include peptone, yeast extract, glucose, NaCl and Na2HPO4. Proper conditions for the synthesis of phospholipase in flasks, 20 l and 250 l fermenters were tested. The maximum increase of the phospholipase activity occurred by the 5-9th hour of microbial growth at pH 6.0-8.0. Further cultivation, foaming, strong aeration, pH increase (over 8.0) reduced the accumulated activity. By fractionation with (NH4)2SO4, ethanol precipitation, protamine sulphate treatment with subsequent Sephadex G-100 gel filtration phospholipase (EC 3.1.4.3) was purified 300-fold from the culture liquid of Bac. cereus str. 504. The preparation was examined electrophoretically in 7% polyacrylamide gel at alkaline pH. The effect of metal salts and EDTA on phospholipase activity was studied. Thermostability, substrate specificity and pH optimum of purified phospholipase were investigated.


[Comparative study of the properties of lipase of microbial origin]. A comparative study of properties of lipases of microbial origin has shown that the pH optimum of the enzymes from Geotrichum asteroides and Penicillium sp. is at pH 7.5 and 5.0, respectively. Lipase from Geotrichum asteroides appears more resistant to high temperatures and pH changes than the enzyme from Penicillium sp. Both enzymes split selectively vegetable oils, especially cotton and sunflower oils. Na cholate and deoxycholate at a concentration of 0.05-0.4% act as hydrolysis activators, particularly with respect to Geotrichum lipase. Na dehydrocholate does not show this effect.


[Method of determination of the activity of glycerol dehydrogenase in the submerged culture of Acetobacter suboxydans]. The paper presents a method for assaying activity of glycerol dehydrogenase activity in the submerged culture of Acetobacter suboxydans. The effect of substrate concentration, content of the submerged culture in the reaction mixture and pH value on the rate of enzymic oxidation of glycerol to dihygrooxyacetone by A. suboxydans has been studied.


A DNA nicking-closing enzyme encapsidated in vaccinia virus: partial purification and properties. Vaccinia virus cores contain an activity which is able to relax both left-and right-handed superhelical DNA. This virus-specific nicking closing enzyme has been highly purified and differs from the corresponding host enzyme in salt optimum, in sedimentation coefficient, and in polypeptide composition as determined on sodium dodecyl sulfate/polyacrylamide gels. The enzyme is probably newly synthesized after the cessation of host protein synthesis which follows virus infection. The most highly purified preparation contains two polypeptides, one of molecular weight 24,000 and the other 35,000. The former polypeptide is a major constituent of the virus (7% of total protein by weight), whereas the latter is present in a much smaller amount (0.2%). Chromatography with denatured DNA-cellulose reveals that the activity is predominately associated with those fractions enriched in the polypeptide of greater molecular weight.


[Desugarization of egg white by microorganisms]. Glucose was eliminated from egg whites, using microorganisms, to prevent melanoidin formation which may damage the product. Desugarization was achieved by means of Acetobacter xylinum, Streptococcus lactis, Propionibacterium shermanii, Pr. petersonii and propionicacid cocci. Optimal conditions of desugarization were found, depending on the physiological characteristics of the above microorganisms. Propionibacterium shermanii may be well used to ferment a liquid egg white. These bacteria have no proteolytic properties and make no use of the egg white. They enrich the egg white with vitamin B12 and propionate, a preserving agent, during fermentation.


H+/ATP ratio during ATP hydrolysis by mitochondria: modification of the chemiosmotic theory. The stoichiometry of H+ ejection by mitochondria during hydrolysis of a small pulse of ATP (the H+/ATP ratio) has been reexamined in the light of our recent observation that the stoichiometry of H+ ejection during mitochondrial electron transport (the H+/site ratio) was previously underestimated. We show that earlier estimates of the H+/ATP ratio in intact mitochondria were based upon an invalid correction for scaler H+ production and describe a modified method for determination of this ratio which utilizes mersalyl or N-ethylmaleimide to prevent complicating transmembrane movements of phosphate and H+. This method gives a value for the H+/ATP ratio of 2.0 without the need for questionable corrections, compared with a value of 3.0 for the H+/site ratio also obtained by pulse methods. A modified version of the chemiosmotic theory is presented, in which 3 H+ are ejected per pair of electrons traversing each energy-conserving site of the respiratory chain. Of these, 2 H+ return to the matrix through the ATPase to form ATP from ADP and phosphate, and 1 H+ returns through the combined action of the phosphate and adenine nucleotide exchange carriers of the inner membrane to allow the energy-requiring influx of Pi and ADP3- and efflux of ATP4-. Thus, up to one-third of the energy input into synthesis of extramitochondrial ATP may be required for transport work. Since other methods suggest that the H+/site significantly exceeds 3.0, an alternative possibility is that 4 h+ are ejected per site, followed by return of 3 H+ through the ATPase and 1 H+ through the operation of the proton-coupled membrane transport systems.


9S binding protein for androgens and progesterone. A steroid binding protein fraction with a sedimentation coefficient of approximately 9 S (molecular weight approximately equal to 200,000) has been identified in 105,000 X g supernatants of several androgen-responsive organs. Highest concentrations were found in epididymis and testis, but small amounts were detected in prostate, seminal vesicle, kidney, submandibular gland, and lung. The 9S protein binds [3H]dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) and [3H]progesterone (4-pregnene-3,20-dione) with equilibrium binding constants of approximately 10(5) M-1 and 10(6) M-1, respectively. The concentration of 9S binding sites in epididymis is approximately 10(-11) mol/mg of supernatant protein, which is at least 10(5) times greater than the concentration of androgen receptor. 9S binding protein appears to be a nonsecretory, intracellular protein and has properties different from the andorgen receptor. It is unretarded on DEAE-Sephadex chromatography at pH 8.0, and its sedimentation rate on sucrose gradients is not altered at high ionic strength (0.4 M KCl). Like the androgen receptor, its binding activity, which is maximal between pH 7 and 9.5, is heat labile, decreased by sulfhydryl reagents, and enhanced by 2-mercaptoethanol. It is suggested that because of its high concentration and low affinity, 9S binding protein may function in the intracellular accumulation of compartmentalization of androgens or progesterone.


[Properties of a preparation of lytic enzymes from a culture of Bacillus subtilis]. The effect of pH, temperature, various salts and other compounds on the activity of the preparation of lytic enzymes from the culture of Bacillus subtilis (lyzosubtilin) was investigated. The preparation was shown to be active in neutral solutions of low ionic strength at 30-50 degrees C. The salts of magnesium, manganese, copper, zinc, lead, mercury, aluminium and iron as well as Tris-buffer and Triton X-100 inhibited lyzosubtilin whereas lactic acid activated it. At 30 degrees C the preparation was stable within the pH range of 5 to 10. Its incubation for 60 min at 60 degrees C resulted in the loss of 50% activity. Lyzosubtilin lyzed cells of gram-positive and gram-negative bacteria, yeast and fungi.


Solid-like character of virus solutions. The solid-like behavior of turnip yellow mosaic virus solutions following the extrusion of viral RNA in alkali was observed with a torsion-fiber balance developed for the purpose. This method provided a direct measurement of the yield stresses required to break or liquefy these solutions. The yield stresses were found to increase and to be less time dependent with increasing concentrations of the virus and they were maximal at room temperatures. If the virus had been damaged, as by freeze-thaw, little or no solid-like behavior could be demonstrated. Purified viral capsids, with or without added RNA, were also inactive. The values for the yield stresses were of the same order as the value reported previously with the use of a magnetic suspension viscometer; hence, the apparent coherency appears unrelated to the magnetic fields generated by the latter instrument. These solutions behaved as typical liquids after the required stress was applied [about 0.005 to 0.17 dyne cm-2 (0.05 to 1.7 micronN cm-2)], these forces being smaller than those usually conferred by ordinary handling.


Adenylate cyclase permanently uncoupled from hormone receptors in a novel variant of S49 mouse lymphoma cells. A novel variant of the S49 mouse lymphoma has been selected from wild-type cells by growth in medium containing the beta-adrenergic agonist terbutaline and inhibitors of cyclic nucleotide phosphodiesterase. In contrast to the situation in the wild-type clone, synthesis of adenosine 3':5'-monophosphate (cyclic AMP) is not stimulated by beta-adrenergic agonists or by prostaglandin E1 either in intact variant cells or in membrane preparations of such clones. However, basal and NaF-stimulated activities of adenylate cyclase [ATP pyrophosphate-lyase (cyclizine), EC 4.6.1.1] are normal, enzyme activity is stimulated by guanyl-5'-yl imidodiphosphate [Gpp(NH)p], and intact cells accumulate cyclic AMP when exposed to cholera toxin. Furthermore, variant cell membranes possess ligand-binding activity consistent with the conclusion that a normal or an excessive number of beta-adrenergic receptors is present. Thus, interaction between the hormone-binding and the catalytic moieties of the adenylate cyclase system is lost. This variant phenotype, designated as uncoupled (UNC), has been stable for more than 100 generations without exposure to the drugs used for selection. Such cells should be useful for the elucidation of methanisms of transmission of information from hormone receptors to adenylate cyclase.


A defined minimal medium for axenic strains of Dictyostelium discoideum. A defined, minimal medium for the cellular slime mold Dictyostelium discoideum is reported.


[Migrating and recurrent superficial phlebitis and Takayasu's disease (apropos of a case)]. This case of recurrent migratory superficial phlebitis is reported because of the highly unusual nature of the lesion observed. The picture was dominated by periphlebitis with inflammatory granuloma, giant cells and elastophagia. When the condition had been present for sixteen months, an aortic arch syndrome developed in an inflammatory context. In this light, various auto-immunological etiologies were considered, among them Takayashu's arteritis of which, in the author's opinion, this would be the first case to be combined with venopathy.


Cryptorchism.

Cryptorchism. Our results from 121 patients as well as data from the literature prove that fertility rates after treatment of uni- or bilateral cryptorchism remain unsatisfactory. There is no statistically significant difference in fertility between a group of patients treated with human-chorionic-gonadotrophin and another group treated by orchidopexy after unsuccessful hormonal therapy. On the other hand, late results in unilateral cryptorchism are to a statistically significant extent better than in bilateral cryptorchism (46/29%). According to our histological findings in maldescended testicles, early treatment (before the age of 3 years) is advocated.


Long-term results of undescended testicle operative treatment. Men affected with unilateral and bilateral undescended testicles have been examined 10 to 20 years after orchidopexy. The examined patients were divided into groups of individuals operated before and after the 8th year of life. Fertility, structure of the genitals, somatotype, psychosexual behavior, and plasma testosterone levels were tested. It was found that a significant number of cryptorchid patients was infertile, especially the bilateral ones. Abnormalities in the structure of the genitals, somatotype, and in some cases psychosexual behavior disorders as well as plasma testoterone levels lower than normal, have also been found.


The vasoconstrictive effect of dopamine in the isolated, perfused rat kidney after catecholamine depletion. In the isolated, perfused kidney of untreated and catcholamine-depleted rats (by 6-hydroxydopamine and reserpine), dopamine (DA) caused a dose-dependent increase in vascular resistance which could be prevented by prior blockade of the alpha-adreno-receptors. The DA-induced vasoconstriction thus appears to be due to a direct stimulation of alpha-receptors in the kidney rather than an indirect sympathomimetic effect through release of noradrena-line from local adrenergic nerve terminals. The effectiveness of the chemical sympathectomy accomplished with 6-hydroxydopamine and reserpine was evaluated by chemical; histochemical and electron microscopical methods.


Role of Pco2 oscillations and chemoreceptors in ventilatory response to inhaled and infused CO2. We have previously shown in the anaesthetized rabbit that the ventilatory response to an increase in Paco2 is greater if that increase is produced by intravenous infusion of hypercapnic blood than by inhalation of CO2 (Linton et al., 1976). The present set of experiments was designed to investigate the reason for this. It was found that the difference in ventilatory response observed in the intact rabbit was abolished by cutting the carotid sinus nerves or by eliminating the pH/Paco2 oscillations in the carotid blood flow. It is concluded that the normally greater ventilatory response to intravenous infusion of hypercapnic blood compared with inhalation of CO2 is due to a respiratory signal derived from Paco2 oscillations and carried in the carotid sinus nerves.


Microflora in the healthy gingival sulcus in man. The roll tube culture technique was utilized to examine quantitatively and qualitatively the predominant cultivable microflora inhabiting the clinically healthy gingival sulcus. Seven periodontists aged 32-54 years were included in the study. From a total of 350 isolates, 85 (24.3%) were obligate anaerobes, 53 (15.0%) were Gram negative, and 197 (56.3%) were categorized as rods. Actinomycetes predominated in three samples. Four samples were dominated by Streptococcus species. The flora as revealed in the present study comprised a markedly lower proportion of Gram-negative organisms than that found at the base of deep periodontal pockets.


Plasma secretin concentration in anaesthetized pigs after intraduodenal glucose, fat, aminoacids, or meals with various pH. The concentration of immunoreactive secretin in portal blood and the secretion from the exocrine pancreas were measured during intraduodenal infusion of isotonic or hypertonic saline, isotonic or hypertonic glucose, aminoacids, fat emulsion, or 0.1 mol X 1(-1) hydrochloric acid in 7 anaesthetized pigs. None of these substances, except hydrochloric acid, had any effect on plasma secretin concentration and pancreatic flow rate and bicarbonate output. Plasma secretin concentration rose significantly from 5.6 +/- 2.7 pmol X 1(-1) (mean +/- S.E.M.) to a peak value of 201.2 +/- 80.5 pmol X 1(-1) 15 min after infusion of hydrochloric acid. Pancreatic flow rate and bicarbonate output increased from 0.51 +/- 0.19 ml X h-1 (mean +/- S.E.M.) to 9.85 +/- 2.33 ml X h-1 and from 52 +/- 11 micronmol X h-1 to 1.004 +/- 290 micronmol X h-1, respectively. During intraduodenal introduction of meals with pH adjusted from 1.0 to 7.0 in 4 pigs amylase was secreted at all pH levels. However, only when pH of the meal was 1.0, resulting in an intraduodenal pH from 1.0 to 1.7 during the stimulation, was a significant increase in plasma secretin concentration and pancreatic flow rate observed from 5.5 +/- 2.8 pmol X 1(-1) (mean +/- S.E.M.) to 115.0 +/- 51.2 pmol X 1(-1) and from 0.20 +/- 0.08 ml X h-1 to 6.25 +/- 2.57 ml X h-1, respectively.


[Bacterial endocarditis: clinical and bacteriological aspects and prognostic factors]. The microbiological, clinical and therapeutic aspects of all (71) cases of bacterial endocarditis admitted to the Hôpital cantonal, Geneva, between August 1970 and October 1974 were reviewed: there was a definite trend towards higher prevalence of acute cases compared to subacute cases. The pathogenic role of S. epidermidis, mostly in cases of prosthetic valve endocarditis, could be demonstrated in several cases. When defined initially by microbiological criteria only, acute endocarditis were characterized by rapid evolution, destruction of the valvular structures (especially aortic valve), and by further evolution under adequate antibiotic therapy: thus, 10/25 patients with acute endocarditis died, whereas the mortality rate in the subacute cases was only 10/46. Many cases in our series showed one or more often frequent embolic phenomena: 70% of the cured cases and 80% of the patients with a fatal outcome. An unfavorable evolution could be correlated with neurologic involvement, cardiac rhythm or conduction disturbances, and/or heart failure; indeed, heart failure due to various mechanisms was the single most frequent cause of death and is presently the main therapeutic problem. Thus, acute infection leading to destruction of the aortic valve and to heart failure still carries a bad prognosis, even if emergency valve replacement is attempted. Finally, 22/30 patients who developed a bacterial endocarditis after oral or urological procedures knew about a heart murmur, but did not receive antibiotic prophylaxis. This clearly shows that emphasis should be put on the elaboration and diffusion of adequate prophylactic regimens.


[Peptic ulcer: new aspects of conservative therapy]. In spite of the large number of preparations, medical therapy of peptic ulcer disease has long been unsatisfactory. Antacids, anticholinergics and diet neither accelerate healing of ulcers nor prevent recurrences. Carbenoxolone affects only gastric ulcers, while some medications exhibit substantial side effects. Cimetidine, a representative of the new generation of H2-receptor blockers which are potent inhibitors of gastric secretion, significantly enhances healing of duodenal ulcers. In addition, favorable effects on gastric ulcers, as well as on bleeding erosions and ulcers in the Zollinger-Ellison syndrome, have been reported. Thus far no severe adverse reactions with cimetidine have been observed, but data on effects of long term use are lacking. Synthetic prostaglandins are not yet sufficiently evaluated for clinical use.


[Gastro-esophageal reflux disease. A review of pathogenesis, diagnosis and therapy]. Gastro-esophageal reflux disease is caused by peptic damage from gastric contents to the distal esophagus. The principal cause of reflux is a decrease in pressure of the lower esophageal sphincter, which normally separates the esophagus from the stomach. Various hormonal, pharmacological or toxic agents are capable of altering resting sphincter tone. Treatment of esophageal reflux disease is a rewarding task for the general practitioner. An algorithm on appropriate use of diagnostic and therapeutic resources is presented.


Localization of nigral dopamine-sensitive adenylate cyclase on neurons originating from the corpus striatum. Nigral basal adenylate cyclase and dopamine-sensitive adenylate cyclase, glutamate decarboxylase, choline acetyltransferase, and tyrosine hydroxylase activities were measured in rats with hemitransections at various levels or with electrolytic lesions of the medial forebrain bundle or the crus cerebri. The loss of nigral dopamine-sensitive adenylate cyclase activity after the various brain lesions was correlated with loss of nigral glutamic acid decarboxylase but not that of tyrosine hydroxylase; nigral choline acetyltransferase was unaffected in all cases. The data indicate that the nigral dopamine-sensitive adenylate cylase activity may be localized on neurons afferent to the nigra, probably originating from the globus pallidus and possibly from the tail of the caudate. The results suggest that dopamine, released from nigral dendrites, may influence dopaminergic activity indirectly by modulating impulses transmitted to the nigrostriatal neurons through the crus cerebri.


Transmitter release during repetitive stimulation: selective changes produced by Sr2+ and Ba2+. The addition of Sr2+ or Ba2+ to the solution bathing the frog neuromuscular junction leads to an increased release of transmitter by each nerve impulse during and following repetitive stimulation. The mechanisms by which Sr2+ and Ba2+ increase release are not the same. Each ion appears to act selectively on a different process involved in transmitter release.


[Periarteritis nodosa and Australia antigen. Comparative study apropos of 25 cases]. The authors compared two series of 27 cases of périateritis over a period of 5 years. The determined the frequency of the nodosa HBs+ (series B) and HBs-- (series A) collected clinical and laboratory signs in both series. There resulted that apart from the hepatic signs constant in series B and absent in series A, the only statistically significant differences were the joint sings and the hypertension more common in series B and the respiratory signs more common in series A. Furthermore, the course of HBs+ cases appears much mote severe than that of HBs-- cases which emphasises the importance of the hepatic involvement but this finding should be interpreted with circumspection for the mode of selection of the patients and the treatment were different in the two series.


[Beta blockaders and general pathology]. The authors review the literature on the undesirable side effects of beta blockaders (excluding the cardiovascular system) and report the new therapeutic propects in psychiatry and in various metabolic disorders. The necessity of sufficient follow up made us choose propanolol as reference product without neglecting acebutolol, pindolol and oxprenolol.


Expression of differentiated functions in hepatoma cell hybrids: IX extinction and reexpression of liver-specific enzymes in rat hepatoma-Chinese hamster fibroblast hybrids. Most of the hybrid clones derived from a cross of Chinese hamster fibroblasts (DON) with rat hepatoma cells (Faza 967) showed preferential loss of rat chromosomes. Two of the hybrid clones retained the rat chromosomes, and both showed extinction of 4 liver-specific enzymes: aldolase B, liver alcohol dehydrogenase, and the inducible enzymes tyrosine aminotransferase and alanine aminotransferase. Subcloning of 1 of these hybrids, which contained 2 sets of hepatoma chromosomes and 1 set of hamster chromosomes, permitted the isolation of some clones which reexpressed 1 or more of the liver-specific enzymes. Liver alcohol dehydrogenase was the most frequently reexpressed enzyme and aldolase B the least. Tyrosine aminotransferase inducibility was reexpressed independently of basal activity, and the enzyme produced by the reexpressing hybrid cells was precipitated by a specific antiserum. No correlation was detected between the presence or absence of the marker chromosomes (large metacentrics) of the hamster parent and the extinction and reexpression of the hepatic enzymes. The results reported confirm and extend to interspecific hybrids the observation of the stable and independent reexpression of tissue-specific enzymes.


Extinction of liver-specific functions in hybrids between differentiated and dedifferentiated rat hepatoma cells. A cross has been performed between dedifferentiated rat hepatoma cells and the differentiated cells from which they were derived. 10 hybrid clones, containing the complete chromosome sets of both parents, show extinction of 4 liver-specific enzymes: tyrosine aminotransferase (E.C. 2.6.1.5), alanine aminotransferase (E.C. 2.6.1.2), and the liver-specific isozymes of alcohol dehydrogenase (E.C. 1.1.1.1) and aldolase (E.C. 4.1.2.13). Moreover, the 4 hybrid clones examined do not produce albumin . The only function of the differentiated parent which is not extinguished in the hybrid cells is inducibility of the aminotransferases. For 3 of the hybrid clones, extinction of 3 of the 4 enzymes is incomplete, but these clones do not differ in modal chromosome number from those which show more complete extinction of the enzymes. Subcloning of several of the hybrids revealed that the phenotype of the hybrids is very stable; 4 subclones showing reexpression of intermediate levels of the enzymes are characterized. These results show that dedifferentiation of the parental cells is not due to the simple loss of some factor required for the maintenance of expression of differentiated functions, and suggest that dedifferentiation is due to the activation of some control mechanism, whose final effect is negative, and which may be a part of the epigenotype of the embryonic hepatocyte.


In vitro inhibition of growth of neisseria gonorrhoeae by genital microorganisms. The ability of microorganisms present in titers of over 10(5)/ml in the vaginal or cervical secretions to inhibit growth of N. gonorrhoeae in vitro was tested. Study of a strain of N. gonorrhoeae against 77 microorganisms demonstrated that most strans of S. epidermidis, S. aureus and the one "Gaffkya anaerobia" interfered with the growth of the N. gonorrhoeae. A minority of strains of S. viridans, Neisseria, Candida and Bifidobacterium demonstrated interference. No strains of enterococcus, diptheroids, aerobic Lactobacillus, Peptostreptococcus, Peptococcus, anaerobic Lactobacillus or Veillonella demonstrated interference.


Reduction of fatal graft-versus-host disease by 3H-thymidine suicide of donor cells cultured with host cells. The effect of the tritiated thymidine (3H-TdR) suicide technique on the ability of donor cells to induce fatal graft-versus-host disease (GVHD) was studied. C57BL/6 (H-2b) spleen cells were stimulated in vitro with irradiated BALB/c (H-2d) Moloney lymphoma cells in mixed culture and 3H-TdR of high-specific activity added to eliminate proliferating cells. The ability of such cells to induce fatal GVHD was assayed by injecting them i.v. into adult BALB/c mice immunosuppressed with cyclophosphamide (180 mg/kg). These cells induced fatal GVHD in fewer mice (52 per cent) than did C57BL/6 cells cultures with BALB/C lymphoma cells but without 3H-TdR (87%) and C57BL/L cells cultured with irradiated C57BL/6 cells with (95 per cent) or without 3H-TdR (86 per cent). Thus, the 3H-TdR suicide technique greatly diminished the ability of cells to induce lethal GVHD.


In vivo and in vitro effects of acute graft-versus-host serum in the rat. Pooled serum from 6- to 8-week-old female Lewis x Brown Norwegian F1 hybrid (LBNF1) rats undergoing acute local graft-versus-host (GVH) reactions was found to have the ability, when compared with normal F1 serum, to increase node weight in a popliteal lymph node weight gain assay in syngeneic animals. Suspension of donor cells in normal F1 serum on one side and corresponding concentrations of GVH serum on the contralateral side resulted in an average increase in popliteal node weight of 28.8 per cent on the side receiving GVH serum. Of the 64 animals tested, 50 had larger nodes on the GVH serum side. This effect was not impaired by heating (56 C, 30 min) or by rapid freezing (-75 C) and thawing of the serum. Preinjection of the serum into the footpads 2 hr before donor cells also gave increased node weights as did injection of the serum i.p. In contrast, GVH serum was found to inhibit unidirectional mixed lymphocyte cultures of seven different allogeneic rat strain combinations, the inhibition ranging from 35 to 74 per cent. In addition, the blastogenic cell responses of three different strains to phytohemagglutinin P were inhibited between 45 and 77 per cent. The relationship between these two phenomena, in vivo increase in node weight and in vitro inhibition of blastogenesis, is not clear and is the object of further investigation.


Generation of suppressor cells in mice immunized with M locus-incompatible lymphocytes. Alloimmunization of mice with M locus-incompatible lymphocytes resulted in the generation of suppressor cells in the immunized host. Lymph node cells from such alloimmunized mice suppressed the in vitro cytotoxic response of normal cells to H-2 alloantigens. The suppression generated was greater than could be accounted for by dilution of the prekiller cell population with cells possibly devoid of cytotoxic potential from M locus preimmunized mice. Using M locus pseudocongenic mice, the suppressive effect was shown to be largely attributable to M locus determinants; restimulation of suppressor cells in culture with the specific M locus was required for suppression of effector cell generation. The in vivo effect of suppressor cells was tested in a graft-versus-host reaction; injection of M locus preimmunized cells into footpads of F1 hybrid mice suppressed the popliteal lymph node enlargement compared with lymph node size after injection of control preimmunized cells. Although the suppressive effect is mainly attributable to M locus determinants, incompatibility for the DBA/2 antigen may add to the suppression. The study of inhibitory effects on T cell cytotoxicity because of serologically undetectable lymphocyte-activating determinants (Mls) could lead to the better understanding of suppressive mechanisms which may allow the growth of syngeneic tumours.


HLA-D compatibility between parent and child: increased occurrence in severe combined immunodeficiency and other hematopoietic diseases. Weak or weak intermediate reactions in one-way mixed lymphocyte culture (MLC) were seen between a patient and at least one parent in the families of 6 of 15 patients with severe combined immunodeficiency disease, 3 of 4 patients with Fanconi's anemia, and 3 of 7 patients with congenital neutropenia (CN). In control family material, weak MLC reactions were seen in 1.4 per cent (4 of 285) of individual parent-child and child-parent combinations or in 2.1 per cent (3 of 143) of the total number of parent-child pairs. The increase in frequency of weak MLC reactions seen in the familes of patients with severe combined immunodeficiency disease and Fanconi's anemia occurred most frequently between mother and patient. This finding could be relevant to the pathogenesis of these diseases. In children with CN, the disease seems to be associated with the HLA antigen B12; in addition, two of the patients with CN appear to be homozygous for HLA-D. Because of the relatively frequent compatibility seen in MLC reactions between parents and children with severe combined immunodeficiency disease, Fanconi's anemia, and CN, it is suggested that those parents could be potential donors for bone marrow transplantation.


A comparison of immune responses against AG-B and non-AG-B antigens, presented alone or together. By exploiting congenic rat strains (HO.B2 and PVG/c) cell-mediated immune responses against Ag-B antigens alone were measured and compared with responses against (1) non-Ag-B antigens and (2) Ag-B and non-Ag-B antigens in combination. It was confirmed that multiple non-Ag-B antigens provoke prompt first-set skin graft rejections, but are much weaker than Ag-B antigens in stimulating both graft-versus-host (GVH) and cytotoxic activity. No evidence of synergistic interaction was found between anti-Ag-B and anti-non-Ag-B responses either by GVH assay or in the generation of cytotoxic cells. Specific partitioning of cytotoxic cells on antigenic monolayers suggested that cytotoxic cells on antigenic monolayers suggested that cytotoxicity is predominantly directed against Ag-B antigens. The measurements of GVH activity consolidate previous work, which suggested that 4.5 to 12% of nonimmune T cells can respond to each Ag-B determined antigenic complex and eliminate the possibility that most of these cells were responding to non-Ag-B antigens. Two principles for measuring GVH activity were compared: (1) 3H-thymidine incorporation into donor lymphocytes at 24 hr after transfer to irradiated F1 hybrid recipients and (2) the popliteal lymph node assay, which depends on a secondary phase of host cell proliferation.


The graft-versus-host reactivity in AG-B/MLR disparate strains of rats. Inbred strains of rats can currently be classified into eight Ag-B groups. Within an Ag-B group, individual strains generally share identity both the Ag-B histocompatibility antigens and mixed lymphocyte responses. In this report we present data from three strains which are Ag-B and mixed lymphocyte reaction (MLR) disparate: KGH (Ag-B7, MLR-1), MNR (Ag-B4, MLR-5), and B3 (Ag-B3, MLR-4). Popliteal lymph node assays involving these three strains and standard inbred strains demonstrate that the graft-versus-host reaction and MLR reactions in the rat are closely related. Positive graft-versus-host reactions were observed only in strain combinations incompatible for the MLR and were unaffected by differences in their Ag-B histocompatibility antigens. The close association of the MLR and graft-versus-host reaction provides additional evidence that the Ag-B/MLR disparity in these strains is the result of natural genetic recombinations within the major histocompatibility complex.


Bone marrow transplantation.

Bone marrow transplantation. Improvements in the results of bone marrow transplantation for the treatment of SCID may be expected by employing purified stem-cell concentrates for patients who do not have a compatible sibling available. Refinements in the purification technique and its monitoring are required, however. For the same category of patients it seems worthwhile to continue attempts at restoration with liver cells from fetuses less than 12 weeks of age. In addition, full protection against infections should be provided for patients expected to develop GVHD, and, therefore, such patients should only be treated in centers where reverse isolation and bacteriologic decontamination can be performed. In view of the rarity of the disease, transplanters should agree on a limited number of graft protocols. For the treatment of bone marrow aplasia, attempts to identify the factors that can serve to predict the occurrence of GVHD in compatible host-donor sibling pairs should be continued. Only when the patients who will develop GVHD can be recognized in advance will it be feasible to fully exploit available GVHD reductive measures. In particular the role of the intestinal microflora should be investigated in this respect. Experimental evidence is presented, suggesting an aggravating influence of microflora on GVHD lesions, which are primarily induced by histocompatibility reactions. For such studies with incompatible siblings, the dog is the best available animal model. For the selective isolation of hemopoietic stem cells for transplantation purposes (as one means of reducing GVHD), methods for rapid identification of stem cells and immune competent cells, respectively, have to be developed. In leukemia, more research is necessary on the factors that play a role in the late complications of bone marrow transplantation. The toxicity of aggressive regimens employed in the eradication of the leukemia should be further analyzed. The collection of autologous normal hemopoietic stem cells from leukemic patients as introduced by Dicke et al. warrants further exploration to see whether these cells may replace the allogeneic transplantation procedure, thus avoiding all the complications generally encountered in GVHD. For all three diseases, it is extremely important to develop a method for the selection of compatible donors among unrelated individuals, because this will at least double the number of candidates for therapeutic bone marrow transplantation. Current progress in histocompatibility typing in the rhesus monkey and the dog makes these species excellent models for such investigations.


Specific absorbed antithymocyte globulin for incubation treatment in human marrow transplantation. The experimental data show that absorption of ATG with liver-kidney homogenate and CLL and LCL cells stepwise removed the hemopoietic toxicity, whereas the specific activity against T lymphocytes remained. Although the mode of action of absorbed ATG could not be tested in the first clinical case, the successful experiments in rodents together with the fact that the incubation treatment was tolerated by the patient may provide a new way of preventing fatal GVH reactions in man.


Other mammalian histocompatibility systems. Skin graft rejection and graft-versus-host reaction across I-subregion differences: are there many more than three H loci within the H-2 complex? The data confirm an earlier finding by Klein et al. that the I region harbors a strong histocompatibility locus, which by exclusion might be assigned to the IA subregion. In addition, it appears that intercalated between the IA subregion and S region there is a minor H locus since (DBA/2 X 4R)F1 rejects skin of 2R in a chronic fashion. In another combination, HTT versus 7R, which differs for the IC, S, and G regions but may also differ for genes between the D and TL locus, a similar chronic rejection pattern was observed indicating minor H gene(s) within or closely linked to the H-2 complex. The data reported here are in concordance with very recently published results by Klein et al..


Nuclear and cytoplasmic RNase-activity in regenerating mouse liver. Nuclear and cytoplasmic RNase activities at pH 5.0 and 7.6 were analyzed in regenerating mouse liver at 6, 12, 24, 48, and 72 h after partial hepatectomy. Two different nucleus-isolation methods were used, one in a EDTA-spermidine medium free from divalent cations, and one in a sucrose medium containing these ions. During regeneration, the cytoplasmic alkaline RNase activity in the sucrose medium was unchanged, but in the spermidine medium showed an increase toward the end of the period. Also the cytoplasmic acid RNase activity was unchanged in sucrose medium, whereas in the spermidine it slightly increased during regeneration. The nuclear alkaline RNase activity showed a notable peak 6 h after the operation and later decreased. Also the nuclear acid RNase activity displayed a similar marked peak 6 h after operation, then decreased, but remained high throughout the period. The nuclear RNase activities were about 1% of the corresponding cytoplasmic RNase activities. The absolute activities varied greatly according to the nucleus-isolation methods. In the controls, the absolute activity of nuclear alkaline RNase was slightly above (1.2 times) that of the corresponding acid activity after the spermidine method. After the sucrose method the nuclear alkaline activity was 2.7 times that of the acid activity. The absoluted activity of cytoplasmic alkaline RNase was slightly above (1.2 times) the acid activity after the spermidine method but after the sucrose method it was only 0.25 times that of the acid activity. In sham-operated animals, cytoplasmic acid and alkaline RNase activities generally were fairly similar to the normal value, but corresponding nuclear activities showed marked variations indicating an influence by anesthesia.


[Characteristics of the serum proteins of cancer patients in an acid medium]. Under condition of nitric acid titration of aqueous and hydrochloride solutions of sera from patients with cancer certain serum proteins become insoluble at higher values of pH as compared to the other proteins of sera. The latter lose solubility at the pH values corresponding to transition to the insoluble state of serum proteins from people without malignant tumours. The results of studies in the temperature regime effect on the found peculiarities of serum proteins from patients with cancer in the acid medium permit assuming that the physical bases of the marked transitions are different. The mentioned regularity is not pronounced with a temperature rise up to 35--40 degree C.


[ATPase activity and fluorescence of myometrial actomyosin in experimental uterine inertia]. A comparative study was performed for actomyosin complexes of the female rabbit myometrium in the state of labour (actomyosin of the control) and secondary uterine inertia (actomyosin of the model). Under the secondary uterine inertia the activity of actomyosin Ca2+- and Mg2+-ATPase decreases. When pH of the medium changes, ATPase of control actomyosin has two peaks of the activity: at rH 6.0 and pH 9.0, that of the model at pH 6.0. Actomyosin of the model and control differs by a degree and rate of superprecipitation, thermal stability and structure. It is supposed that the structural changes in actomyosin under the secondary uterine inertia occur due to accumulation of the metabolism products, the level of which with this pathology is beyond the limits of the adaptation potentialities of the organism.


[Intracellular nucleodepolymerase of bacteria, representatives of the Proteus and Providencia groups. Its isolation and properties]. High activity of enzymes, splitting native, denaturated DNA, deoxyribooligonucleotides and RNA, was observed in cell free extracts of bacteria--representatives of 5 strains of Proteus-Providencia. Some properties of nucleases were studied in cell free extracts. In the bacteria studied DNAases were thermolabile proteins, which were completely inactivated at 50-60 degrees, RNAases were more thermostable. The pH optima of the DNAases were at pH 9.0-11.0 in cell free system; RNAases were maximally active at pH 8.0-9.0


[Role of divalent cations in the structural organization of the peroxisomal membrane]. Factors, which affected the stability of peroxisomal membrane in vitro, were investigated. The decrease in the activity of catalase at neutral and alkaline pH was prevented by addition of Ca2+, Mg2+ and Ba2+; at the same time EDTA, EGTA and o-phenantroline decreased the stability of peroxisomes. All the effects were temperature-dependent. Ca2+ did not prevent the injury of peroxisomes during hypotonic lysis, but increased the electrostatic interactions of enzymes with the peroxisomal membrane. These data suggest that at neutral and alkaline pH the peroxisomal membranes had a large negative charge on their surface, which affected the stability of peroxisomes in vitro.


[Labilization of lysosomal and peroxisomal membranes in the kidneys preserved by transrenal gas perfusion]. The total, free and unprecipitated activity of lysosomal (acid DNAase, acid RNAase, acid phosphate, acid beta-galactosidase) and peroxisomal (catalase, oxidase of D-amino acids) enzymes were studied in dog kidney cortex during storage of the tissues in solution of rheopolyglucin and under conservation of the kidney tissue by transrenal gas perfusion in hypothermia within 3 and 7 days. Labilization of lysosomal and peroxisomal membranes was observed during storage both in unperfused and in oxygenated kidney. Mechanisms of formation and functional significance of the alterations observed in structure of lysosomes and peroxisomes are discussed.


[Role of salivary ribonuclease in pathogenesis of periodontosis]. In patients with periodontal disease a distinct increase in secretion of salivary acidic and alkaline RNAases was found. The RNAases activity in mixed saliva correlated with the intensity of degradation of periodontal tissues during loss of alveolar layer in aged Wistar rats and the spontaneous periodontal disease in cats. In experiments with golden hamsters salivary RNAase was found to penetrate through mucosa in active form. The purified salivary RNAase inhibited the protein biosynthesis in rabbit gingiva. Intensive atrophic alterations were produced in periodontal tissues of Wistar rats by means of purified salivary RNAase.


Subtypes of depression--diagnosis and medical management. Depression is both a common and a greatly undertreated illness in the United States today. The focus of this review is a definition of the characteristics of four subtypes of depression which appear to be differentially sensitive to four different classes of medications. The tricyclic antidepressants should be used for patients with unipolar depression and vegetative symptoms. Lithium appears to be most effective for bipolar depressives. The monoamine oxidase (MAO) inhibitors are best used for patients with atypical depression. Antipsychotic medications appear to be useful for depressed patients with psychotic symptoms or agitation. Recent pharmacokinetic and biochemical data, including serum lithium levels, plasma tricyclic levels, and the predictive ability of pretreatment urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels are also reviewed.


[New variant of glucose-6-phosphate dehydrogenase (G-6-PD "Kaluga") from erythrocytes of a patient with chronic nonspherocytic hemolytic anemia]. Properties of a new form of glucose-6-phosphate dehydrogenase (G6PD) from erythrocytes, called "Kaluga", are described. The enzyme was isolated from erythrocytes of a patient with chronic non-spherocytic hemolytic anemia; in the blood cells 20% of the G6PD activity was maintained as compared with normal state. The partially purified enzyme was shown to be unstable in electrophoresis, it possessed a biphase type of pH-optima; Km value for NADP was decreased for glucose-6-phosphate Km value was normal. The thermostability of G6PD was normal at 46 within 1 hr.


Drugs for peptic ulcer.

Drugs for peptic ulcer. Conservative management of peptic ulcer relies on the use of drugs as an adjuvant to the time-honored measures of avoiding stress, reducing gastric secretion, and regulating the diet. Alkalies neutralize acid and anticholinergic drugs partly inhibit secretion.. Both are widely used but are often inadequate to control symptoms. Carbenoxolone appears to have a more specific effect in promoting healing of gastric ulcers and has now been used for 15 years. Its role in the treatment of gastric ulcer can be critrically examined, particularly in relation to how this influences surgical management. Recently introduced compounds know as histamine H2-receptor antagonists have a profound effect in inhibiting gastric secretion. Early experience in patients with duodenal ulcer indicated the efficacy of these compounds in promoting healing. These potent new drugs are likely to influence strongly the management of patients with duodenal ulcer, and this may affect the indications for surgery.


[Degradation of polysomes of skeletal muscles of rats during preservation in solutions with different pH]. Alterations in properties of RNP-particles from rat sceletal muscles on storage of the preparations in buffer solutions at various pH were analyzed by means of centrifugation in sucrose gradients. Within 3 days of incubation at 20 the distribution of RNP-particles in the sucrose gradient was changed relatively slightly; which was due to the low activity of endogenous ribosomal RNAase. The fraction of the UV-absorbing material in polysomes was gradually decreased on storage and the fraction of subunits was increased respectively. The most distinct alterations were observed on incubation of the preparations at pH 6.0; the RNP-particles were apparently destructed after acidification of the medium.


[Inhibition of bacterial agmatinase by substrate analogs]. Activity of agmatinase (EC 3.5.3.11) from Proteus vulgaris was studied in presence of guanidine derivatives of agmatine as substrates. The guanidine derivatives, containing carboxyl group, did not interact with the enzyme. An inhibitory effect developed if the carboxyl group was esterified. For exhibition of the effect the length of hydrocarbon radical in ligand and presence of hydrophobic groups were important. One of the most effective inhibitor was N-isoamylene agmatine (K1=0.001 M). Compounds, containing an amino- or guanidine group at the position opposite to the guanidine end and possessing the hydrocarbon chain not less that C4 were shown to be substrates of agmatinase.


Progress in the treatment of acute gastroduodenal mucosal lesions (AGML). This article presents an analysis of acute gastroduodenal mucosal lesions (AGML) based on a review of current literature and the personal experience of the authors. The pathology of AGML involes two distinct types of lesions, namely, superficial erosions confined to the acid-secreting gastric mucosa and presenting as erosive hemorrhagic gastritis, and acute ulcers that occur in the alkaline gastric mucosa and duodenum. The etiology of these two lesions is very likely different. Acut gastroduodenal ulcers, best known as stress ulcers, are probably "peptic" lesions, whereas erosive hemorrhagic gastritis appears to be due to pathologic back diffusion of hydrogen ions caused by a breakdown of the gastric mucosal barrier as a result of endogenous factors, such as gastric mucosal ischemia, and sometimes exogenous factors, such as alcohol, urea, and acetylsalicylic acid. Catecholamine hypersecretion resulting from severe stress, such as occurs in hypovolemia, sepsis, and hypercapnea, contributes to ischemia of the gastric mucosa by producing splanchnic vasoconstriction. The key to the diagnosis of AGML is early endoscopy in all cases of upper gastrointestinal bleeding. Therapy for AGML should begin with a trial of medical measures directed at restoring effective perfusion of tissues and removing hydrogen ions from the stomach by gastric washing. Medical therapy is effective in 80% of patients with erosive hemorrhagic gastritis, but surgical treatment is usually required in acute gastroduodenal ulcer. When surgery is necessary for either type of lesion, vagotomy with hemigastrectomy appears to be the most effective operation. The personal experience of the authors has involved 36 patients with AGML who were treated in three periods between 1968 and 1976. The mortality rate of patients with AGML has been reduced from 50% in the first 2 years to zero in the last 2 years by the use of emergency endoscopy for diagnosis, appropriate medical therapy, properly timed and executed surgery, and, most recently, selective angiography.


The effect of glucagon on pancreatic secretion and plasma secretin in dogs. The inhibitory effect of glucagon on pancreatic exocrine secretion induced by endogenously released secretin was studied in 4 dogs with chronic pancreatic fistulas and open gastric fistulas. After a constant level of pancreatic secretion was established by intraduodenal hydrochloric acid perfusion (9 mEq/hr), glucagon (30 microng/kg-hr) was administered intravenously for 1 hr. Compared to a separate control study in which dogs received intraduodenal HC1 alone, glucagon caused a significant decrease in both pancreatic volume flow and bicarbonate output. Glucagon had no effect on pancreatic protein secretion, and circulating levels of endogenously released secretin remained unchanged. It is concluded that the inhibitory effect of glucagon on pancreatic secretion is not mediated through inhibition of secretin release. The chemical homology between glucagon and secretin suggests that glucagon may mediate its inhibitory action by competing with secretin at the level of the pancreatic receptor site.


Prevalence of drugs among drivers arrested for drinking and driving in Finland. A combined thin layer and gas chromatography system was developed for qualitative and quantitative analysis of drugs in biological samples after extraction with heptane-isoamyl alcohol. Both acidic and basic extraction procedures were used. Special methods were used for the extraction and detection of salicylates, isoniazid, and morphine. Particular attention was given to the detection of psychostimulants; though these drugs have seldom been found in drinking drivers in Finland they are commonly found in Sweden. Two percent of all suspected drinking drivers were also suspected of concommitant drug use, which led to primary sampling of urine. Of 100 such drivers, 24 had blood alcohol levels (BALs) which were negative and 18 of that 24 had drugs in their sample. Seventy-six of the 100 had positive BALs and 25 of the 76 had drugs in their samples. Of the randomly chosen 100 suspected drinking drivers, 5 had drugs in their samples, and 4 of these 5 had positive BALs. The benzodiazeomes were the most commonly detected drugs. No stimulants were found in our subjects.