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Duration of action of analgesic supplements to anesthesia. A double-blind comparison between morphine, fentanyl and sulfentanil.
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In a double-blind trial, in a total of 45 patients, sulfentanil was compared with fentanyl and morphine in equipotent doses, as a narcotic supplement to anesthesia. Initially, morphine was shown to have a significantly longer duration of effect than fentanyl and sulfentanil, which for the first 3 doses had similar durations of action to each other. Later doses of fentanyl, however, had an extended effect, presumably because of cumulation. This was not seen with sulfentanil.
| 21,506
|
Relapsing polychondritis. A clinical, pathologic-anatomic and histochemical study of 2 cases.
|
A 57-year-old man and a 70-year-old woman with relapsing polychondritis are reported. The man, suffering from arthralgias, respiratory obstruction, external ear and sanddle-nose deformities, conjunctivitis and irido-cyclitis, died after 4 years from airway obstruction because of tracheal and bronchial collapse. The woman is alive 8 months after the development of respiratory obstruction, probably caused by radiographically demonstrated tracheal obstruction, a saddle-nose deformity and hearing impairment. Microscopically, the involved cartilages showed degenerative and slight inflammatory changes and were eventually replaced by fibrous tissue. Histochemical studies, utilizing staining with Alcian blue at controlled electrolyte concentrations (Scott technique) and at controlled pH:s, with or without digestion with bacterial chondroitinase ABC; and staining with the PAS-method, with or without diastase digestion, revealed a complete or relative loss of glucosaminoglycans and glycogen. A biosynthetic defect is considered unlikely to be the primary pathogenetic mechanism of relapsing polychondritis. Histological and histochemical examination of biopsies from involved cartilages contribute to a definite diagnosis.
| 21,512
|
Electron microscopy of an oligomeric protein stabilized by polyfunctional cross-linking.
|
Oligomeric proteins can be intramolecularly cross-linked with polylysine in a reaction in which a water soluble carbodiimide mediates an amide linkage between the protein carboxyl groups and the epsilon-amino groups of polylysine. Studies carried out with a cytochrome p-450 indicate that a small number of molecules in a population which has been cross-linked in this way retain important features of their tertiary and quaternary structure when negatively stained and examined in the electron microscope. Use of the method in determining the subunit geometry of oligomeric proteins is discussed.
| 21,540
|
Smallpox eradication in Rajasthan, India.
|
In 1962, when the smallpox eradication programme was launched in India, there were 3909 reported cases in Rajasthan. Mass vaccination was introduced but had little impact on the incidence of the disease; in 1970, 4074 cases were reported and in 1971, the reported incidence (4821 cases) was the highest in India. Changes in the vaccination technique, the use of a new and potent vaccine and the introduction of a new strategy based on surveillance and containment of outbreaks, rather than mass vaccination, brought good results. By 1972, only 1970 cases were reported and endemic smallpox was eliminated from Rajasthan before the launching of the intensified all-India compaign in July, 1973. In 1974, epidemics were occurring in the neighbouring states of Uttar Pradesh and Madhya Pradesh as well as in Bihar and West Bengal. But in that year, there were only 10 new smallpox outbreaks in Rajasthan, all originating from imported cases. The organization and progress of the eradication campaign and the history of smallpox eradication in Rajasthan are described in this communication.
| 21,557
|
Mechanism of active chloride transport by urinary bladder of the Colombian toad.
|
In order to investigate the mechanism of active chloride transport, experiments were performed to verify the previous report that removal of potassium from the solutions bathing the urinary bladders of Colombian toads induced a reversal of short-circuit current (RSCC) and active chloride transport. The present experiments confirmed these findings. However, there was no correlation between the magnitude of the RSCC and the chloride transport. Furthermore, removal of chloride from the mucosal bathing solutions did not markedly affect the RSCC, indicating that the chloride transport was electrically silent. Removal of bicarbonate from the bathing solutions eliminated the RSCC, and acetazolamide inhibited both the RSCC and net chloride transport. These findings suggest a relationship between chloride and hydrogen ion transport. Inhibition of sodium transport by removal of sodium or addition of ouabain or amiloride has previously been shown to produce an RSCC. In the present experiments these same maneuvers caused an RSCC and induced net chloride transport. It is concluded that active chloride transport by Colombian toad bladder is stimulated by inhibition of sodium transport. The inhibition of active chloride transport by acetazolamide suggests a possible role for carbonic anhydrase in this process.
| 21,569
|
An evaluation of a unique new antipsychotic agent, sulpiride: effects on serum prolactin and growth hormone levels.
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Sulpiride is a new and chemically different neuroleptic. In a study of 16 severely ill schizophrenic patients, this compound displayed definite evidence of antipsychotic activity while producing few adverse reactions. The relative absence of extrapyramidal side effects may indicate that sulpride has a low potential for producing tardive dyskinesia. Two patients who did not develop significant increases in prolactin levels did show a definite therapeutic response to sulpiride. Thus it appears that central dopaminergic blockade in the hypothalamic area is not a prerequisite for antipsychotic activity.
| 21,571
|
Regional quality control survey of blood-gas analysis.
|
We undertook an external quality control survey of blood-gas analysis in 16 laboratories at 13 hospitals. All samples were prepared in the laboratories under investigation by equilibration of blood or serum with gas mixtures of known composition. pH of serum was measured with no significant bias but with an SD of random error 0.026 pH units, which was almost twice the SD of the reference range (0.015). An acceptable random error (half SD of reference range) was not obtained in a longitudinal internal quality control suvey although there were acceptable results for buffer pH in both field and internal surveys. Blood PO2 was measured with no significant bias but with SD of random error 1.38 kPa which reduced to 0.72 kPa by excluding one egregious result. The latter value was just over half of the SD of the reference range (1.2 kPa). PCO2 of blood was also measured without significant bias but with a much smaller SD of random error of 0.28 kPa (by excluding one egregious result), which was again just over half the SD of the reference range (0.51 kPa). Measurements of blood PO2 and PCO2 seem generally acceptable in relation to their respective reference ranges but measurements of pH were unsatisfactory in both internal and external trials.
| 21,606
|
Release of antral and duodenal gastrin in response to an intestinal meal.
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In dogs prepared with isolated, innervated antral pouches, intraduodenal perfusion with liver extract at pH 7, with the atrum buffered at pH 7, resulted in a significant release of gastrin selectively from the antrum and from the duodenum. Acidification of the meal to pH 1 abolished both antral and duodenal gastrin release, whereas acidification of the antrum abolished only the antral gastrin response. After antrectomy, liver extract at pH 7 caused a diminished but significant release of duodenal gastrin. These studies provide evidence that an intestinal meal may release (in addition to a specific intestinal phase hormone) gastrin from the intestine, and from antrum, by means of a pH-sensitive mechanism which may involve a humoral agent (enterobombesin?) from the small bowel.
| 21,638
|
[Acid-base status in the blood of domestic pigs during exhausting locomotor stress of small and medium intensity].
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Twenty-two fattening pigs were stressed until their rectal temperatures had reached 42 degrees C. The means of stress included walking on moving conveyor belt at ambient temperatures between 22 degrees C and 27 degrees C and relative humidities between 69 and 98%, belt speeds of 0.7 m/s, 1.3 m/s or 0.7 m/s, and stimulation by means of a forcing rod. Rectal temperature, respiratory frequency, lactic acid level in blood plasma, pH, as well as pCO2 and base excess in the blood were measured prior to, during, and after stressing. Gasping was strongly pronounced due to severe alkalisis, but it was somewhat mitigated on running on the belt with exposure to additional stress on account of lactic acid accumulation in the plasma.
| 21,642
|
Effect of substrates and effectors on the reversible inactivation of pig spleen phosphofructokinase by adenosine triphosphate.
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1. To investigate the mechanism of the reversible inactivation of pig spleen phosphofructokinase by ATP, the effect of order of addition of reactants (substrates, effectors and enzyme solution) was studied by preincubating the enzyme before assay with various combinations of its substrates and effectors. 2. Preincubation of the enzyme with MgATP or ATP at pH7.0 before addition of fructose 6-phosphate caused a rapid and much greater inhibition of activity than that observed when the reaction (carried out at identical substrate concentrations) was initiated with enzyme. 3. The rapid inhibition caused by preincubation with ATP, together with the sigmoidal response to fructose 6-phosphate and activation by AMP, were all blocked by prior photo-oxidation of the enzyme with Methylene Blue, which selectively destroys the inhibitory binding site for ATP [Ahlfors & Mansour (1969) J. Biol. Chem.244, 1247-1251]. 4. Fructose 6-phosphate, but not Mg(2+), protected phosphofructokinase from inhibition during preincubation with ATP in a manner that was sigmoidally dependent on the fructose 6-phosphate concentration. 5. Mg(2+), by protecting the enzyme from the inhibitory effect of preincubation at low pH (7.0) and by preventing its activation during preincubation with fructose 6-phosphate, demonstrated both a weak activating effect in the absence of the other substrates and a stronger inhibitory effect in the presence of fructose 6-phosphate. 6. Positive effectors (K(+), NH(4) (+), AMP and aspartate) protected the enzyme from inhibition during preincubation with MgATP in proportion to their potency as activators, but citrate potentiated the ATP inhibition. P(i) significantly slowed the inactivation process without itself acting as a positive effector. 7. The non-linear dependence of the initial rate of the unmodified enzyme on protein concentration (associated with increased positive homotropic co-operativity to fructose 6-phosphate) was intensified by preincubation with ATP and abolished by photo-oxidation. 8. The results are interpreted in terms of an association-dissociation model which postulates that protonation, at low pH, of a photo-oxidation-sensitive inhibitory site for ATP allows more rapid dissociation of an active tetramer to an inactive dimeric species.
| 21,659
|
A study of antidepressant activity of some indole alkylamines.
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The antidepressant characteristics of three indole alkylamines were investigated and compared with phenelzine and imipramine by utilising specific pharmacological tools like reserpine, amphetamine, tryptamine and tetrabenazine for determining their possible mechanism of action. Amongst the three indole compounds investigated, indole-3-(2-aminopropyl)-acetate (U-14 164E), indole-3(2-aminobutyl)-d-acetate (u-17 312E) and beta-phenethylhydrazine (phenelzine) produced complete antagonism to reserpine induced sedation, hypothermia as well as facilitation of convulsive seizures. Some of these features suggest that MAO inhibition might be a common mechanism of action of these indoles. The potentiation of CNS effects of tryptamine by these compounds is an outstanding feature of MAO inhibitors, while imipramine is ineffective. Qualitative differences between these indoles and imipramine are evident in the tetrabenazine test. The potentiation of amphetamine induced motor excitation and pentobarbitone narcosis has been explained.
| 21,669
|
Substrate and substrate analogue binding properties of Renilla luciferase.
|
Luciferase from the anthozoan coelenterate Renilla reniformis catalyzes the oxidative decarboxylation of luciferin consuming 1 mol of O2 per mol of luciferin oxidized and producing 1 mol of CO2, 1 mol of oxyluciferin, and light (lambdaB, 480 nm) with a 5.5% quantum yield. In this work we have examined the binding characteristics of luciferin, luciferin analogues, and competitive inhibitors of the luciferin-luciferase reaction. The results show that luciferin binding and orientation in the single luciferin binding site of luciferase are highly specific for and dependent upon the three group substituents of the luciferin molecule while the imidazolone-pyrazine nucleus of luciferin is not directly involved in binding. Anaerobic luciferin binding promotes a rapid concentration-dependent aggregation of luciferase which results in irreversible inactivation of the enzyme. This aggregation phenomenon is not observed upon binding of oxyluciferin, luciferyl sulfate, or luciferin analogues in which the substituent at the 2 position of the imidazolone-pyrazine ring has been substantially altered.
| 21,679
|
Interaction of oligoribocytidylates with T7 DNA in neutral and acid media.
|
Oligoribocytidylates of chain length 4 to 12 were found to interact with native T7 DNA at neutral and slightly acid pH. The results suggest that binding occurred at deoxycytosine clusters which may be displaced by the oligomers at neutral pH, while a local triple-stranded structure would be formed at acid pH. Transcription of DNA-(Cp)n complexes by Escherichia coli RNA polymerase showed a decrease in level without affecting the specificity of the transcription, suggesting that oligocytidylate binding did not occur on the promoters.
| 21,684
|
Effects of pH on the properties of normal and 5-fluorouracil-containing tRNAs.
|
Transfer RNAs isolated from Escherichia coli B grown in the presence of 5-fluorouracil (FIUra) show variations in their aminoacylation levels when compared with normal samples. Some of these variations result from the more stringent aminoacylation reaction conditions required for FIUra-tRNAs. Increasing the reaction pH from 7 to 9 for example, generally causes a lowering of amino acid acceptance by the analog-containing tRNAs, while leaving control samples largely unchanged. This decreased activity appears to result primarily from fluorouracil ionization, which in turn disrupts intramolecular hydrogen bonding and promotes an overall increase in the molecular dimensions of FIUra-tRNAs at elevated pH values. Sensitivity to pH differes with the amino acid examined, with lysine showing dramatic changes and glutamine and proline being largely unaffected.
| 21,694
|
Selective tumor DNA synthesis inhibition: in vivo prodrug activation by an exogenous enzyme.
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Using the combination of alpha-L-arabinofuranosidase from Aspergillus niger with beta-peltatin A-alpha-L-arabinofuranoside, the selective effect of a new cancer of chemotherapy method based on a pH-dependent activation of cancerostatic prodrugs by exogenous enzymes was studied. In comparative experiments the selectivity of prodrug activation was measured by 3H-thymidine incorporation in tumor and normal tissues of CBA mice inoculated im with the transplantable mammary carcinoma, MA-21224. The results show that this special type of carrier principle may lead to a higher degree of selectivity than the usual direct application of cancerostatic drugs.
| 21,745
|
Oxidation of alpha-hydroxybutyrate by human serum.
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2-Hydroxybutyrate is enzymically oxidized by the LDH of human serum. Optimal concentrations of hydrogen ion, substrate and coenzyme for this oxidation by sera from patients with disease of the heart or liver have been determined at 37 degrees C. The linearity of this reaction is limited to a point at which an assay procedure employing a 2-hydroxyburyrate substrate seems unsuitable.
| 21,765
|
Carfecillin: antibacterial activity in vitro and in vivo.
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Carfecillin, the alpha-phenyl ester of carbenicillin, hydrolyses rapidly in the presence of serum or body tissues to liberate carbenicillin but hydrolysis is less rapid in aqueous solution. The activity of carfecillin in antibacterial tests in vitro depends upon the extent of hydrolysis to carbenicillin, and in conventional serial dilution tests carfecillin shows an antibacterial spectrum generally similar to that of carbenicillin due to extensive hydrolysis. However, in tests in which the extent of hydrolysis is reduced, carfecillin displays lesser activity than carbenicillin against gram-negative bacilli and greater activity against gram-positive cocci. In the presence of serum carfecillin is hydrolysed rapidly to carbenicillin and the activity shown is solely that of carbenicillin. Unlike carbenicillin, carfecillin is well absorbed in mice after oral administration, producing significant carbenicillin blood concentrations and the compound is as effective by the oral route in the treatment of various experimental mouse infections as is parenteral carbenicillin.
| 21,771
|
Release of spasmogens from rat isolated lungs by tryptamines.
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Tryptamine and 5-hydroxytryptamine (5-HT) infused through the pulmonary circulation of rat isolated lungs released a spasmogen resembling slow reacting substance of anaphylaxis which we have denoted SRS-T and a PGE-like activity. SRS-T was not extractable from Krebs solution by several organic solvents at neutral or acid pH. It is therefore unlike other types of SRS activity. The PGE-like release had a threshold at about 2 microgram/ml of tryptamine or 5-HT and did not increase with increasing doses (up to 10 microgram/ml); this release was abolished by methysergide, BC 105 and BW 501c67 but not by morphine. Comparison of agonist potencies of 5-HT and tryptamine on rat stomach strip and rat pulmonary artery and of antagonist potencies of methysergide, BC 105 and morphine on these tryptamine receptors lead to the conclusion that the release receptors are unlike either of the myotropic receptors. In terms of antagonist specificity the release receptors are closest to those in rat stomach strip.
| 21,802
|
[Pharmacologic peculiarities of natural and synthetic alpha-adrenomimetics].
|
The mechanical response of the isolated rat vas deferens to four alpha-adrenomimetic substances has been studied. The four test substances were noradrenaline, octopamine, 2-phenylethylamine and 2-(1-naphthylmethyl)imidazoline (Privin). Examination of the cumulative dose/response curves showed both qualitative and quantitative differences. Octopamine gave an alpha value (intrinsic activity) greater than that of noradrenaline; Privin proved to be a partial agonist but with affinity greater than that of noradrenaline. Various qualitative differences were also observed suggesting a possible explanation based on labilization of the membrane.
| 21,809
|
[Anti-inflammatory activity of benzo(c) phenanthridine derivatives and possible mechanisms of action (author's transl)].
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Of five newly synthesized benzo[c]phenanthridine derivatives tested, the two compounds, BPD-I and BPD-II were found to have potent anti-edematous activity with intraperitoneal administration to S.D. rats. BPD-I showed a marked inhibitory effect against acute inflammation such as induced rat paw edema and leucocyte emigration and protein exudation by means of CMC pouch method and capillary permeability enhancement induced by various phlogists. This compound also inhibited subacute and chronic inflammatory responses such as granuloma formation induced by croton oil or cotton pellet. The anti-inflammatory activities of this compound resembled those of hydrocortisone. The inhibitory effects of carragenan edema and capillary permeability enhancement by ATP were strikingly reduced in adrenalectomized rats suggesting involvement of the hypophysis-adrenal systems. Rat serum corticosterone level and hepatic tyrosine aminotransferase activity (TAT) were then measured after BPD-I injection. The serum corticosterone level was increased and shortly after the elevation of corticosterone, hepatic TAT levels also increased. Thus it is concluded that the corticosterone release from adrenal gland plays a role in the anti-inflammatory action of BPD-I.
| 21,834
|
Rapid measurement of an index of testosterone binding to serum binding globulin using ion exchange columns.
|
DEAE cellulose "mini" columns at pH 7.4 retain testosterone (T) bound to testosterone binding globulin (TeBG), which can be eluted at pH 2. Small 1:2 diluted serum or plasma samples are incubated with a tracer dose of tritiated T in pH 7.4 Tris buffer at 37 C then chilled and placed on columns at 4 C. Free and albumin bound T are washed off columns with pH 7.4 Tris buffer and columns are eluted with pH 2 Tris into vials for scintillation counting. After a simple mathematical correction for the small residual fraction of albumin bound T eluted at pH 2, we obtain a measure of TeBG binding of T which is highly correlated (r = .945) with that determined by dialysis. The method is quick, reproducible and applicable to serum or plasma volumes of 50 to 200 microliter. A single operator can process 100 samples in approximately 4 h.
| 21,888
|
Auditory word discrimination in male children diagnosed as having minimal brain dysfunction.
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Investigated auditory word discrimination skill in children diagnosed as having minimal brain dysfunction (MBD), a heretofore unexplored topic in the study of MBD. A lack of auditory discrimination skill seems relevant to learning deficiency in language acquisition, a typical sign of MBD. The present study tested the hypothesis that phonemic aural discriminations would be difficult to make for boys diagnosed as having MBD. Errors and nonresponses made while Ss performed an extended auditory word discrimination task were compared between a group of 26 boys diagnosed as having MBD and a matched normal group. As expected, the MBD group had a significantly higher error rate than the normal group even when Ss were discriminating easy word pairs composed of dissimilar items (e.g., reading, math). These and other results suggested that the MBD group was very susceptible to fatigue even while motivated to perform well and while able to improve with practice. The relatively inferior performance of the MBD group was interpreted as resulting directly from a lack of auditory discrimination skill and indirectly from fatigue and its accompanying attention loss.
| 21,890
|
Patient characteristics and expectancy measures as factors that influence the expectancy-improvement relationship.
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A recent study found factored measures of patient's expectancies for therapeutic gain significantly correlated with 1 of 15 objective measures of treatment outcome for the hospitalized patients. A subsequent study of the same relationship that used unfactored expectancy measured with a diagnostically homogenous sample of patients found the patients' expectancies significantly correlated with 10 of the same 15 measures of improvement. This study reexamined the initial expectancy-improvement data using unfactored measures of expectancy. The overall results showed that characteristics of samples of Ss and the adequacy of expectancy measures both significantly influence the results of tests of the expectancy-improvement relationship.
| 21,891
|
The enzymic interconversion of acetate and acetyl-coenzyme A in Escherichia coli.
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Mutants of Escherichia coli K12 have been isolated that grow on media containing pyruvate of proline as sole carbon sources despite the presence of 10 or 50 mM-sodium fluoroacetate. Such mutants lack either acetate kinase [ATP: acetate phosphotransferase; EC 2.7.2.1] or phosphotransacetylase [acetyl-CoA: orthophosphate acetyltransferase; EC 2.3.1.8] activity. Unlike wild-type E. coli, phosphotransacetylase mutants do not excrete acetate when growing aerobically or anaerobically on glucose; their anaerobic growth on this sugar is slow. The genes that specify acetate kinase (ack) and phosphotransacetylase (pta) activities are cotransducible with each other and with purF and are thus located at about min 50 on the E. coli linkage map. Although Pta- and Ack- mutants are greatly impaired in their growth on acetate, they incorporate [2-14C]acetate added to cultures growing on glycerol, but not on glucose. An inducible acetyl-CoA synthetase [acetate: CoA ligase (AMP-forming); EC 6.2.1.1] effects this uptake of acetate.
| 21,941
|
Adsorption of a phage tail-like bacteriocin to isolated lipopolysaccharide of Rhizobium.
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Purified lipopolysaccharide (LPS) from the bacteriocin sensitive strain Rhizobium lupini i6-2 was shown to neutralize the killing activity of the bacteriocin. In the electron microscopical preparation the phage tail-like bacteriocin appears to be adsorbed to the LPS; the tail sheath is contracted and the fibres are oriented towards the LPS ribbon. In contrast, no interaction was observed between the bacteriocin and the LPS of two resistant strains of Rhizobium (16-2/Ii and 16-3). The inactivation of the bacteriocin by LPS depends on salt concentration, pH, and temperature. The receptor activity of LPS was destroyed by mild acid hydrolysis and by treatment with deoxycholate, which indicates that the micellar structure of the LPS is necessary for bacteriocin adsorption. The chemical composition of the 16-2 LPS was compared to that of the LPS of two resistant strains. In the case of 16-2/ii LPS minor modifications suffice to confer resistance against the bacteriocin.
| 21,942
|
Effects of denervation on the neuraminidase activity of slow and fast muscles of rabbits.
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The presence in skeletal muscles of rabbits of neuraminidase activity on sialyl lactose was demonstrated. By comparing the specific activity of this enzyme in different control muscles, it was shown that it was 2.3 times higher in the slow than in the fast muscles. Seven days after denervation, we observed a significant increase of activity in fast muscle and a significant decrease of activity in slow muscle. These results, together with previous data, are in favour of the hypothesis that turnover of muscle glycoconjugates is under a type-specific neural control.
| 21,944
|
Nature of acid-induced fluorescence of 17alpha-methyltestosterone.
|
The fluorescence of the 17alpha-methyltestosterone-trichloroacetic acid reaction product, 1,2,10,15,16,17-hexahydro-10,17,17-trimethylcyclopenta[alpha]phenanthren-3-one, in strong acid was investigated. Structural requirements for fluorescence were derived from absorption and fluorescence studies of related phenanthrenones and cinnamylidene compounds possessing a similar chromophore. All compounds showed fluorescence intensity that was structure and pH dependent. Fluorescence is attributed to both enol and protonated species.
| 21,952
|
Pleural effusions.
|
Many different conditions result in the accumulation of pleural fluid. A diagnostic thoracentesis should be performed on all patients with pleural effusion from whom pleural fluid can be easily obtained. Empirically we have found that when the pleural effusion is more than 10 mm thick on the lateral decubitus roentgenogram, pleural fluid is easily obtained. At least 30 cc fluid should be obtained and distributed to the various laboratories as outlined in Table 2. The results of these tests will show whether the fluid is a transudate or an exudate. If the fluid is a transudate, no further diagnostic procedures need be directed towards the pleura. If the fluid is an exudate, the diagnosis will frequently be made by these original tests and therapy for the pleural disease can be instituted. If the diagnosis has not been made, the results of these tests should lead to a rational diagnostic attack.
| 21,999
|
Isocitrate dehydrogenase of Tetrahymena pyriformis.
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We have studied the isocitrate dehydrogenase of Tetrahymena pyriformis. This enzyme is able to utilize both NAD and NADP, but kinetic studies suggest that the enzymatic activity with NAD is not of physiological signifance. Some of the factors that might regualte the NADP-dependent isocitrate dehydrogenase were also studied. This enzyme has an absolute requirement for divalent cations; Mg,+ and Mn2+ will serve as cofactors but the latter is more effective than the former. It is known that this enzyme is subject to a concerted inhibition by oxaloacetate and glyoxylate. Either glyoxylate or oxaloacetate alone also are capable of inhibiting the enzyme although higher concentrations are required. We have found concerted inhibition also for the NAD-dependent isocitrate dehydrogenase from rat liver and yeast. The activity of the Tetrahymena pyriformis enzyme is inhibited by NADPH. This inhibition is competitive with NADP. The Ki and Km values are, respectively, 20 micrometers and 18 micrometers.
| 22,034
|
Unfolding and refolding occur much faster for a proline-free proteins than for most proline-containing proteins.
|
The kinetics for unfolding and refolding of a parvalbumin (band 5) have been examined as a function of pH near the transition region, using stopped-flow techniques. This protein is rather unusual in that it has no proline residues, and therefore serves as a good example to test the hypothesis that the rate-limiting step seen in denaturation reactions is due to the cis-trans isomerization of proline peptide bonds in the denatured state. The kinetics for parvalbumin unfolding and refolding are complex, with the data being resolvable into two fast phases at 25 degrees. The slower of the two phases seen for the parvalbumin is about 100 to 500 times faster than the slow phase seen for proline-containing proteins under the same conditions! These results argue strongly in support of the proline isomerization hypothesis. It is also suggested that the slower phase seen for parvalbumin and the second-slowest phase seen for proline-containing proteins might be due to the cis-trans isomerization of peptide bonds of non-proline residues.
| 22,075
|
Oxygen intermediates and mixed valence states of cytochrome oxidase: infrared absorption difference spectra of compounds A, B, and C of cytochrome oxidase and oxygen.
|
A study of the near-infrared absorption spectra of three oxygen compounds of membrane-bound cytochrome oxidase (ferrocytochrome c:oxygen oxidoreductase; EC 1.9.3.1) shows that the formation of compound A (oxycytochrome oxidase) causes no significant infrared absorbance changes at -103 degrees. At -64 degrees, the formation of compound C from the mixed-valence state of the oxidase leads to increased absorption at 740-750 nm. The formation of compound B at -84 degrees from the fully reduced state of the oxidase causes increased absorption at 790-800 nm. Further oxidation of cytochrome oxidase results in increased infrared absorption at 820-830 nm at -60 degrees. The position of the infrared absorption band in compound C thus depends at least upon the oxidation-reduction state of heme a and its associated copper atom. Compound C contains two types of oxidized (cupric) copper; that associated with heme a is initially oxidized, and that associated with heme a3 is oxidized as a second step in the reaction with oxygen. Compound C exhibits a unique intense absorption band at 606-609 nm that is tentatively assigned to a charge transfer interaction between heme a3 in the reduced state and its associated copper in the oxidized state, with heme a and its associated copper in the oxidized state.
| 22,080
|
Fungal proteases and the mammalian kinin system: I. Brinolase-catalyzed kinin formation and S2160 hydrolysis.
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Brinolase, a fungal protease advocated for thrombolytic therapy, released kinin peptides from semi-purified kininogens of the human, rabbit, guinea pig, and mouse, and moreover cleaved an arginyl bond of the chromogenic peptide S2160. Its kinetics demonstrated marked differences from the mammalian protease trypsin. Whereas trypsin liberated 100% of the available kinin in 30 min at pH 8, brinolase generated a maximum of only 22% under optimal conditions, viz. incubation of 5 microgram/ml enzyme at pH 4.7 for 5 min. Longer incubations yielded less detectable kinin. This maximal release at acidic pH was not due to increased kininogen consumption, nor was it inhibited by the acid protease inhibitor pepstatin. Evidence is presented that brinolase, unlike trypsin, might both release and destroy kinins.
| 22,111
|
Cytidine 3',5'-monophosphate (cyclic CMP) formation in mammalian tissues.
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Mammalian tissues possess the capacity to synthesize cytidine 3',5'-monopHosphate (cyclic CMP) via the enzymatic conversion of cytidine 5'-triphosphate to cyclic CMP by cytidylate cyclase. Cyclic CMP formation occurs best in the presence of manganese or iron, at neutral pH, at 37 degrees C, in the absence of detergents, and with whole tissue homogenate fractions. Thus, mammalian tissues are capable of synthesizing not only cyclic AMP and cyclic GMP, but also cyclic CMP.
| 22,127
|
Enzyme histochemical study on hepatoma--the relation between enzyme activity and histological type.
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The activities of gamma-glutamyl transpeptidase (gamma-GTP), alkaline phosphatase (A-p), and leucine aminopeptidase (LAP) were examined in 18 cases of hepatomas. The activity of gamma-GTP was most remarkable in the hepatoma consisting of small to medium-sized tumor cells showing the least atypism. The enzyme activity found in the type composed of large tumor cells resembled that of normal liver and was considered to be the most mature form of the neoplasm. This enzyme was not found in the immature type composed of small typical tumor cells. A-P activity was seen in only a few cases of hepatoma; conspicuous in one case showing immature features and sporadically in one case with florid histological pattern. The activity of this enzyme could not be confirmed in the type demonstrating marked gamma-GTP activity. LAP activity was noted in the majority of cases, especially marked in the medium-sized tumor cells, but there was hardly any connection between this enzyme and histological type. In general, the cases demonstrating positive gamma-GTP activity tended to show LAP activity. Although the activity of gamma-GTP and that of A-p usually showed an inverse relation, all three enzymes demonstrated almost equal activity in the type showing a florid histological pattern.
| 22,215
|
Influenza virus antigens in human leukocytes after oral administration of live tissue culture influenza A monovaccine.
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Influenza A virus antigens were detected in leukocytes by immunofluorescence. After intravenous inoculation of the A/Moscow/16/65 (H2N2) vaccine strain to chickens, cytoplasmic antigens of the virus were observed in mononuclear leukocytes from 24 to 72 hours post inoculation (p.i.). The course of antigen detectability was similar after two repeated inoculations of the virus. After oral vaccination of human volunteers with a live tissue culture influenza A monovaccine from the X-47 (H3N2) recombinant viral antigens were also found in mononuclears; the maximal number of antigen-positive cells was observed at 24 hours p.i. The method of membrane immunofluorescence proved to be the most sensitive for antigen detection; it revealed a considerable decrease in the number of antigen-positive cells after repeated administration of the virus to volunteers. This fact may possibly reflect the development of antiviral resistance in the process of vaccination.
| 22,233
|
Infectivity of DNA recovered from cells persistently infected with SV5 paramyxovirus.
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Infectivity of DNA isolated from L cells chronically infected with SV5 paramyxovirus was demonstrated by inoculation of continuous RH and HEp-2 cells. Infectivity of the DNA was completely abolished by treatment with deoxyribonuclease or by alkaline hydrolysis but did not change after treatment with ribonuclease and specific anti SV5 serum. The virus obtained as a result of transfection caused haemadsorption in susceptible cells and was neutralized by specific antiserum like the prototype SV5 strain.
| 22,236
|
Intrapartum fetal asphyxia: clinical characteristics, diagnosis, and significance in relation to pattern of development.
|
The clinical and fetal heart rates and acid-base characteristics and their sequelae have been reviewed in 587 patients. The relevant clinical factors in the asphyxia group were the preterm fetus, the intrauterine growth retarded fetus, maternal toxemia, and midforceps delivery. The duration of the developing metabolic acidosis in the asphyxia group ranged from terminal to the last two hours of labor. Marked patterns of total decelerations and moderate and marked patterns of late decelerations are of predictive value in the diagnosis of intrapartum fetal asphyxia with a trend to an increased incidence in the longer duration categories, between four and two hours prior to delivery, and a significant increase in all categories during the last two hours of labor. The significance of intrapartum fetal asphyxia to the newborn infant is evident from the low Apgar scores, increased incidence of moderate and severe respiratory distress syndrome, and central nervous system complications in the asphixia group in relation to the normal group.
| 22,248
|
The age dependence of bile acid metabolism in rats.
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The age dependence of bile acid metabolism in rats was investigated and the following results were obtained. 1) Synthesis rate, pool size and total secretion decreased in old rats (24 month) significantly compared to young rats (6 weeks). 2) The quotient of taurine to glycine conjugates is is significant lower in old rats compared to young rats. 3) The lithogenic index remains unchanged in all age groups. 4) Old rats show a significantly higher Km for cholic acid uptake, whereas the diffusion coefficient is decreased. The possible influence of humoral factors on age dependent regulations of bile metabolism is discussed.
| 22,256
|
[Caustic lesions of the esophagus in the child].
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On the basis of a study involving 21 children treated over a 10 year period, the authors describe a method for the management of a child following the ingestion of a caustic fluid: emergency oesophagoscopy to determine the extent and nature on the lesions, in severe forms, alimentation gastrostomy, which would seem to be preferable to parenteral alimentation, is carried out, on the 21st day, a new endoscopic and radiological assessment, permitting distinction between those cases which are cured and those progressing to stenosis. In this latter group, the choice is made between dilatations and oesophagoplasty on the basis on the lesions present and the development of complications during dilatation.
| 22,280
|
[Postoperative complications in esophageal surgery].
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Apart from certain complications which may follow any surgical procedure, the authors sought to emphasise in particular the problems posed by fistulae occurring after oesophageal surgery. They draw a clear distinction between cervical fistulae which, draining adequately, do not affect the vital prognosis, merely prolonging the period of hospitalisation, and intrathoracic or sub-diaphragmatic fistulae, with a grave prognosis and which pose delicate problems of re-operation, drainage and intensive care. They feel that the possibility of prevention of these digestive fistulae must be stressed, combining the most meticulous surgical technique with appropriate pre- and postoperative care.
| 22,284
|
[Pulmonary complications of esophagectomy for carcinoma of the middle third of the esophagus].
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The authors studied 20 patients undergoing operation for a carcinoma of the middle third of the oesophagus during the period January 1972 to April 1975. Postoperative pulmonary complications are extremely common in such patients. All the patients had pulmonary function study results which were compatible with this type of surgery. All underwent resection with oesophagogastric anastomosis via a left thoracophrenolaparotomy. Of the 20 patients, 14 suffered from one or more episodes of acute respiratory insufficiency, some related to pneumonia. On the basis of various associated clinical, radiological, biological, evolutive and histopathological criteria, five types of pulmonary complication were distinguished: 1-Shock lung; 2-Infective pneumonia; 3-Traumatic pulmonary disease; 4-Acute cor pulmonale; 5-Lung disease of undetermined origin. Twelve patients died as a result of pulmonary complications, 11 early (before the 16th day). One patient only died as a result of rupture of the oesophagogastric anastomosis.
| 22,291
|
Nitrogen fixation, denitrification, and pleomorphic growth in a highly pigmented Spirillum lipoferum.
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A strain of Spirillum lipoferum with intense red pigmentation was isolated from the roots of Cynodon dactylon "Coastal." This isolate vigorously reduced acetylene when grown in N-free, Na-malate, semisolid agar, and it was identical to S. lipoferum strain SP7 by standard taxonomic tests. Both S. lipoferum SP7 and the C. dactylon root isolate displayed the unique features of being denitrifiers as well as N2 fixers. The N2-dependent growth curve was biphasic: cells in younger cultures showed the characteristic spiral shape and motility, but those in older cultures developed larger, nonmotile, cystlike forms. Nitrogenase activity seemed associated only with younger spiral forms. The red pigment may be a b- or c-type cytochrome. The strong red color, which this strain develops, could be used as a marker in evaluating soil inoculation experiments.
| 22,311
|
[Pathomorphology of the vessels of the microcirculatory bed of the serous membranes in systemic allergic vasculitis].
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The impregnation method and micropreparation were used to study the morphological changes in vessels of the microcirculatory channel of serous membranes in systemic allergic vasculites. Inflammatory and sclerotic processes in arterioles, precapillaries, capillaries, postcapillaries, and venules were found to be accompanied by regeneration changes and complicated adaptative alteration of the intact structures of the terminal vascular bed. The paper also presents morphological data reflecting decompensation processes in local lymph and blood flow.
| 22,322
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Gated proton conduction via the coupling factor of photophosphorylation modified by N,-N-orthophenyldimaleimide.
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The membrane bound coupling factor of photophosphorylation is studied after pretreatment of broken chloroplasts with the bifunctional N,N-orthophenyldimaleimide under energization of the thylakoid membrane by mild flashing light. The proton conduction of the membrane is monitored both via the electrochromic absorption changes and via selective pH-indicating dyes. It is found that the coupling factor, after interaction with N,N-orthophenyldimaleimide during the preillumination period, shortcircuits one of the two protons pumped inside after excitation of chloroplasts with one short flash of light. In contrast to the low proton conductivity of the unperturbed thylakoid membrane (relaxation time for a proton gradient greater than 5s), this extra proton channel leads to a partial relaxation of a proton gradient within a few ms. Although limited to only one proton per electron, this extra proton conducting pathway is not otherwise specific. It operates with protons resulting from both Photosystem I and Photosystem II activity. In addition it operates with protons already present in the internal phase before firing of the exciting light flash. These effects are prevented by the presence of ATP (but not GTP) during the preillumination period. It is suggested that the modified coupling factor is gated open by the light induced electric field across the thylakoid membrane while self closing after passage of one proton per activated coupling factor.
| 22,346
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Effects of dietary vitamin B-2 and vitamin E on the delta9-desaturase and catalase activities in the rat liver microsomes.
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The effects of dietary vitamin B-2 and vitamin E on delta9-desaturation of stearoyl-CoA, catalase, glutathione peroxidase, superoxide dismutase and electron transport components in rat liver microsomes have been investigated. delta9-desaturase activities were decreased on diets deficient of vitamin B-2, E and supplemented with E. Among the peroxide-scavenging enzymes, only the catalase activity in microsomes correlates significantly with delta9-desaturase activity. In vitro addition of bovine catalase had no effect on microsomal delta9-desaturase activity on control diet. However, it enhanced the delta9-desaturation in microsomes on vitamin B-2-deficient diet which contained low catalase and high superoxide dismutase activities, compared to those in microsomes of control diet. It is suggested that the hydrogen peroxide-generating and -decomposing systems may play an important role on the delta9-desaturase activity in microsomes.
| 22,349
|
[Effect of dipyroxime on the concentration of nicotinamide coenzymes and adenylate nucleotides in the myocardium and liver of rats poisoned with phthalophos].
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Experiments were conducted on rats; in depression of blood cholinesterase activity by 68.6 percent phthalafos proved to decrease the myocardial nicotinamide coenzymes content on account of reduction in the amount of the oxidized forms. In the liver phthalafos diminished the content of oxidized and reduced forms of nicotinamide coenzymes, decreased the level of adenylic nucleotides chiefly at the expense of ATP. Diproxim prevented the changes caused by phthalafos in blood cholinesterase reactivation to 47.5 percent. It is supposed that the capacity of diproxim to normalize the oxidative processes in the cell by acting upon the nicotinamide coenzymes and adenylic nucleotides underlies its antidote action.
| 22,370
|
Possible sites of origin of human plasma ribonucleases as evidenced by isolation and partial characterization of ribonucleases from several human tissues.
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The ribonucleases (RNases) present in a number of human tissues, including heart, brain, lung, and kidney, were purified, partially characterized, and compared in their properties to the previously described RNases from human liver, spleen, pancreas, and serum. The enzymes appeared to fall into two major classes: liver-spleen type RNase and plasma-type RNase. These two types of enzymes were present in varying proportions in all tissues examined. The extent to which the tissues studied possibly contribute to serum RNase levels is discussed.
| 22,399
|
In vivo oxidation of reduced nicotinamide-adenine dinucleotide phosphate by paraquat and diquat in rat lung.
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Intravenous injection of rats with 156 mumol/kg of paraquat or 140 mumol/kg of diquat produced, within 60 min, a sharp drop in the ratios of NADPH to NADP in lung. The effect persisted for a time period of at least 24 h. Exposure to 100% oxygen enhanced the toxicity of both compounds without substantially amplifying changes in the NADPH/NADP ratio. Lungs retained the capability to synthesize adenine nucleotides de novo. Electron microscopic studies showed that both paraquat and diquat damage type I alveolar cells, but only paraquat produces type II cell lesions. Although bipyridylium herbicides produce acute oxidation of NADPH in vivo, there seems not to exist a straightforward relationship between this event and cell damage.
| 22,404
|
Antiarrhythmic properties of 5-(3-tert-butylamino-2-hydroxy)propoxy-3,4-dihydrocarbostyril hydrochloride (OPC-1085), a newly synthesized, potent beta-adrenoreceptor antagonist.
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1. The antiarrhythmic properties of 5-(3-tert-butylamino-2-hydroxy)propoxy-3,4-dihydrocarbostyril hydrochloride (opc-1085) were compared with those of propranolol and pindolol using various kinds of preparations for experimental arrhythmia in dogs. 2. Although OPC-1085 was the most potent drug to antagonize adrenaline-induced arrhythmia in animals anaesthetized with either pentobarbitone sodium or halothane, it was scarcely effective on ouabain-induced arrhythmia in pentobarbitone sodium anaesthetized animals. 3. When these compounds were administered intravenously to conscious dogs 24 h after two-stage ligation of the anterior descending artery, ectopic ventricular beats of coronary ligation-induced arrhythmia were reduced while regular sinus beats were simultaneously increased. 4. OPC-1085 was very effective on aconitine-induced arrhythmia in dogs anaesthetized with pentobarbitone sodium. The effective dose was similar to that of propranolol but about fifteen times less than that of pindolol. 5. It is concluded that different potencies among these beta-adrenoreceptor antagonists against various kinds of experimental arrhythmias cannot be simply deduced from any one of the following properties; beta-adrenoreceptor antagonism, intrinsic myocardial stimulation, local anaesthetic and so-called quinidine-like effects.
| 22,416
|
Characterization of the adrenergic activity of carbuterol (SK&F 40383-A).
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Carbuterol is a beta-adrenergic bronchodilator with selectivity for bronchial smooth muscle relative to cardiac and vascular tissues of several species including man. The present studies were undertaken to further characterize its adrenergic profile. In vitro studies demonstrated that carbuterol was a direct acting beta-adrenergic agonist, not dependent on endogenous catecholamine release, and was devoid of alpha-adrenergic agonist activity. The activity of the racemate was shown to reside primarily in the l-enantiomer. Carbuterol inhibited immunologically induced release of histamine and slow reacting substance of anaphylaxis from passively sensitized fragmented rhesus monkey lung and also inhibited passive cutaneous anaphylaxis in rats. The relatively weak stimulant activity of carbuterol on beta1 receptors mediating both rate and force of contraction was confirmed in anesthetized open-chest dogs. In the anesthetized cat, carbuterol was significantly less potent than isoproterenol in decreasing diastolic blood pressure, increasing heart rate, and decreasing the tension and degree of fusion of incomplete tetanic contraction of the soleus muscle.
| 22,441
|
Plasma cyclic GMP: response to cholinergic agents.
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S.c. injections of cholinergic agents, carbachol, methacholine and bethanechol, into fasted rats caused rapid increases in the plasma concentration of cyclic GMP, with a sharp peak at 5--10 min after the injection. Acetylcholine gave rise to a rapid accumulation of cyclic GMP in plasma only when administered together with physostigmine which produced only a slight, if any, potentiation of the action of the cholinesterase-resistant choline esters. Cyclic AMP also increased after these drugs, but only subsequently to the rise of cyclic GMP; the primary action of the cholinergic drugs appeared to be the increase in cyclic GMP. Atropine was effective not only in abolishing the increase in plasma cyclic GMP induced by cholinergic drugs but also in lowering the baseline level of cyclic GMP. It was concluded that the plasma concentration of cyclic GMP could serve as a good parameter of cholinergic activity in rats.
| 22,443
|
Fluoride uptake by Streptococcus mutans 6715.
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The short-term kinetics of fluoride uptake by cells from 20- to 22-h cultures of Streptococcus mutans strain 6715 were studied using rapid filtration and centrifugation techniques. Saline-suspended organisms were diluted with fluoride-containing solutions buffered at four different pH values (2.0, 4.0, 5.5, and 8.2). Fluoride disappearance from the medium was inversely related to pH and to the duration of the exposure at any given pH. The uptake was rapid and extensive at the lower pH values and decreased as the pH increased. Media fluoride concentrations subsequently increased; i.e., fluoride was released from the cells. The presence of glucose, cyanide, or iodoacetate did not influence the results. However, preincubation of the cells in fluoride-free buffers, followed by the addition of fluoride, reduced fluoride uptake markedly. Cell-to-media pH gradients were determined by the distribution of 14C-labeled 5,5-dimethyl-2,4-oxazolidinedione. Fluoride uptake was found to be a function of the magnitude of the pH gradient (P less than 0.001). It is hypothesized that fluoride uptake occurs by the diffusion of hydrogen fluoride and the subsequent trapping of ionic fluoride.
| 22,490
|
Immunochemical characterization of Lymantri dispar NPV hemagglutinin: protein-carbohydrate interaction.
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The agglutination of chicken erythrocytes by Lymantria dispar nuclear polyhedrosis virus polyhedrin has been shown to provide specific virus identification. Selected mono- and oligosaccharides, present in blood group substances, were assayed by the Land-steiner hapten inhibition technique for specific inhibition of polyhedrin hemagglutination. N-acetylgalactosamine and N-acetylglucosamine inhibit to the greatest extent; galactosamine, glucosamine and fucose to a lesser extent. The hapten inhibition data suggest that a monosaccharide possessing an equatorial 2-acetamido group interacts most avidly with the polyhedrin-combining site. Bergold demonstrated that the polyhedrin dissociates into six subunits at a pH greater than 10.0. Diafiltration equilibrium and Scatchard analysis indicate that N-acetylgalactosamine binds most avidly to the polyhedrin (Kd = 1.7 X 10(-6)) which contains six available sites, suggesting that one hemagglutination site resides on each subunit. Since virions derived in vivo and polyhedrin are serologically cross-reactive, this protein-carbohydrate interaction may play a role in host infectivity by providing a receptor site for virus attachment to target cells.
| 22,517
|
Phosphagen and lactate contents of m. quadriceps femoris of man after exercise.
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Muscle biopsies were taken from the m. quadriceps femoris of man immediately after termination of dynamic and isometric exercise. These were analyzed for adenosine triphosphate (ATP), adenosine 5'-diphosphate (ADP), adenosine 5'-phosphate (AMP), phosphorylcreatine (PC), creatine, pyruvate and lactate. Regardless of type, intensity, and duration of the preceding exercise, a general pattern of the relation between high-energy phosphates and lactate content could be observed. PG showed a nonlinear relationship to the muscle lactate content. The ratio of ATP to ADP appeared to decrease linearly when lactate content increased. The relationships are believed to be the consequence of a steady-state condition where muscle pH is one of the major determining factors.
| 22,533
|
Studies on human alpha-lactalbumin: radioimmunoassay measurements in normal human breast and breast cancer.
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A sensitive and specific radioimmunoassay for human alpha-lactalbumin, a milk protein, has been developed in order to examine the effect of prolactin on the human breast in normal and diseased states. Samples of milk from nursing mothers and from men and women with galactorrhea were found to contain milligram concentrations of this protein. In serum, 8 of 25 normal men and 18 of 44 normal women had detectable concentrations of alpha-lactalbumin. Significantly higher levels of alpha-lactalbumin were found in 17 of 19 women during pregnancy who were not actively lactating. All nursing mothers were found to have distinctly elevated serum alpha-lactalbumin concentrations. In a group of 17 female patients with phenothiazine induced prolactin elevations (mean 29.4 ng/ml), the mean serum alpha-lactalbumin of 17.3 ng/ml was significantly higher than in normal female volunteers. Patients with gynecomastia were not noted to have elevated alpha-lactalbumin. In vitro, homogenates of normal breast and carcinoma tissue from the same individuals revealed that in 9 of 17 patients alpha-lactalbumin was present in higher concentrations in normal than in cancerous tissue. Overall, alpha-lactalbumin was found in 48.5% of homogenates and 41% of organ cultures of normal breast tissue from cancer patients. In contrast, it was present in only 19% of homogenates and 21% of cultures of carcinoma tissue, indicating that the cancer tissue may lose its ability to produce alpha-lactalbumin. Differences in biologic behavior were found in some tumors. In 2 cases homogenates of breast cancer tissue had much higher concentrations of alpha-lactalbumin than the normal tissue, and in 3 of 33 tumors studied in organ culture prolactin increased alpha-lactalbumin output.
| 22,554
|
Aerobic and anaerobic bacteriology of acute otitis media in children.
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Tympanocentesis and aerobic and anaerobic cultivation of the middle-ear fluid obtained was performed through one or both tympanic membranes of 62 children with acute otitis media. Aerobic bacteria alone, predominantely pneumococcus and Hemophilus influenzae, were isolated from 57% of patients; anaerobic organisms alone, most commonly Propionibacterium acnes and Peptococcus, from 15%. Thirteen percent yielded mixtures of aerobes and anaerobes, and several had multiple aerobic or anaerobic agents. The isolation of only anaerobic bacteria, supported in some patients by gram-stain observations of middle-ear fluid, suggest that these bacteria, especially Petococcus, may occasionally play a direct role in acute otitis media.
| 22,590
|
The microfilaria of Brugia timori (Partono et al. 1977 = Timor microfilaria, David and Edeson, 1964): morphologic description with comparison to Brugia malayi of Indonesia.
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The microfilaria of Brugia timori was compared with microfilariae of Indonesian strains of periodic and subperiodic Brugia malayi using alcohol-fixed (stained) and formalin-fixed (unstained) preparations. As noted by other observers of the Timor microfilaria, the absence of a stained sheath in Giemsa preparations, a long cephalic space with a length-to-width ratio of about 3:1, and a great overall body length are features which most readily distinguish this parasite. Additionally, B. timori has greater numbers of single row nuclei in the terminal column of body cells and a lesser bulge of the cuticle surrounding nuclei in the distal portion of the tail than does B. malayi. About 60% of B. timori microfilariae were exsheathed in haemalum-stained thick blood films. Brugia timori microfilariae were found to be distinct from microfilariae of B. malayi by comparing percentages of total body length included between the cephalic tip and major internal anatomic markers.
| 22,593
|
The influence of adrenalectomy on monoamine oxidase and NADH cytochrome c reductase in the rat heart.
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The effect of adrenalectomy on the activities of monoamine oxidase (MAO), NADH cytochrome c reductase (NCR), succinate dehydrogenase, malate dehydrogenase, fumarase, NAD+ nucleosidase and acid phosphatase in homogenates of rat hearts was examined. Besides MAO only the NCR activity increased. However, both the total and the rotenone-insensitive NCR activities increased, with that of the rotenone-insensitive being about half of the total, which indicated that the effect of adrenalectomy was exerted on components of this enzyme localized on both the inner and outer membranes of the mitochondrion. The lack of effect on the other enzymes suggests that adrenalectomy has a relatively selective action on MAO and NCR, and does not work by a generalized increase in protein synthesis or by an effect on the FAD cofactor. The MAO increase was seen with a variety of substrates, and was due to a rise in Vmax without change in Km. The response to adrenalectomy in the summer differed from that seen in the winter. The possible reasons for these effects of adrenalectomy are discussed.
| 22,598
|
Estimation of the degree of crystallinity in digoxin by X-ray and infrared methods.
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The X-ray procedure for estimation of the degree of crystallinity in digoxin is based upon measurement of the total X-ray scattering and the scattering from crystalline regions of the drug. The infrared procedures are based upon measurement of the peak height ratios, 1775/1618 and 3095/1618 cm-1. Correlation between results obtained by the two methods is good. These methods are of value in the physico-chemical characterization of digoxin, particularly as the properties may be altered by comminution.
| 22,603
|
Identification of the in vitro N-oxidized metabolites of (+)- and (-)-N-benzylamphetamine.
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This study has identified (+)- and (-)-N-benzyl-N-hydroxyamphetamine as metabolites after incubation of both (+)- and (-)-N-benzylamphetamine with fortified rabbit liver homogenates. The isomeric hydroxylamine metabolites were identified using the techniques of g.l.c., t.l.c. and combined g.l.c.-mass spectrometry (ms) and by comparison with results from reference samples. An additional novel metabolic product was identified after incubation of N-benzylamphetamine which had properties consistent with that of N-benzyl-amphetamine nitrone.
| 22,624
|
Degradation of (--)-ephedrine in solution and during extraction with diethyl ether.
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Significant losses occurred during the extraction of small quantities of ephedrine from aqueous media using either regular or analytical grades of diethyl ether. The losses were, at least in part, caused by reaction of the ephedrine with aldehydic impurities in the ether; three substituted oxazolidines were identified, using g.l.c. and g.l.c-ms. These and one other oxazolidine were synthesized and characterized by g.l.c., g.l.c.-ms, nmr and infrared spectroscopy. Alternative mechanisms for ephedrine breakdown were considered. Ephedrine was separately oxidized by three different oxidizing agents and also irradiated by ultraviolet light; the products were characterized by g.l.c., g.l.c.-ms. A method for the purification of diethyl ether is recommended to minimize ephedrine breakdown.
| 22,719
|
(1-(3-(Phenothiazin-10-yl)propyl)-4-piperidinyl)phenylmethanones, a novel class of long-acting neuroleptic agents.
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In previous studies the phenyl-4-piperidinylmethanone moiety was shown to be a neuroleptic pharmacophore. A short series of [1-[3-(phenothiazin-10-yl)propyl]-4-piperidinyl]phenylmethanones was prepared and tested for neuroleptic activity using the blockade of d-amphetamine lethality in aggregated mice and suppression of conditioned avoidance behavior as the end points. Most compounds were shown to be potent neuroleptic agents and two were found to possess a long duration of action.
| 22,753
|
Selective monoamine oxidase inhibitors. 1. Compounds related to 4-aminophenethylamine.
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A series of derivatives of 4-aminophenethylamine was synthesized and their effect on monoamine oxidase (MAO) activity in the brain was evaluated. Several of the new compounds were potent and selective inhibitors of the A form of MAO but were poor inhibitors of the B form. The most active compounds were the 2,6-dichloro-(9) and the 2-halogeno-4-dimethylaminophenethylamines (5, 6, and 8). Some of the compounds also strongly antagonized aggressive behavior in isolated male mice. This effect was correlated to the MAO inhibition when tyramine was used as substrate. Significant correlations between MAO inhibition in vivo and potentiation of the syndromes produced by 5-hydroxytryptophan and tryptamine and antagonism of reserpine sedation were obtained.
| 22,755
|
Antidepressant agents. 9. 3,3-Diphenylcyclobutylamines, a new class of central stimulants.
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3,3-Diphenylcyclobutylamine (4), N-methyl-3,3-diphenylcyclobutylamine (6), and N,N-dimethyl-3,3-diphenyl-cyclobutylamine (7) have been prepared and tested as potential antidepressant agents. The secondary (6) and tertiary (7) amines strongly decrease the accumulation of NA and 5-HT in brain slices in vitro and in vivo. The cyclobutylamines also cause motor stimulation. The most potent compound in this respect is the tertiary amine 7. The increase in locomotion is not blocked by pretreatment with phenoxybenzamine, methergoline, or alpha-methyltyrosine. Pretreatment with pimozide or reserpine reduces the hyperactivity induced by 7. This hyperstimulation seems to be caused by a mechanism of action which differs from that of amphetamine. 7 may cause increase in locomotion by release of dopamine from granular stores.
| 22,757
|
Disseminated intravascular coagulopathy during experimental pneumococcal sepsis: studies in normal and asplenic rhesus monkeys.
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Disseminated intravascular coagulation (DIC) was induced in both normal and asplenic rhesus monkeys by intravenous challenge with Streptococcus pneumoniae. Our observations in the infected monkeys have led us to conclude that (1) pneumococcal capsular polysaccharide (PCP), immune complexes and complement may not have primary roles in the initiation of DIC; (2) intact pneumococci may be catalysts for the development of DIC; (3) the initial event in DIC may be activation of Hageman factor; and (4) evidence of activation of Hageman factor-dependent systems is present regardless of severity of infection.
| 22,758
|
Impaired maturation of pre-synaptic cholinergic nerve terminals in the superior cervical ganglia after administration of guanethidine and dexamethasone.
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The role of post-synaptic cells in the development of pre-synaptic cholinergic nerve terminals has been investigated in immature rat superior cervical ganglia (SCG) and adrenals employing chemical agents which prevent the normal maturation of post-synaptic cells. A marked atrophy of ganglion adrenergic neurons after guanethidine administration was accompanied by the complete failure of normal maturation of choline acetyltransferase (ChAc) activity in the presynaptic endings. However, the same treatment failed to alter the levels of ChAc in the mature ganglia despite the marked atrophy of adrenergic neurons. Administration of dexamethasone resulted in a growth retardation of ganglion neurons as well as adrenal chromaffin cells reflected by the lower levels of tyrosine hydroxylase and dopamine-beta-hydroxylase than those in untreated tissues. The levels of ChAc were significantly lower in the ganglia, but not in the adrenals when treatment was started immediately after birth. These results support the view that the normal synapse formation in the SCG depends on the normal maturation of adrenergic neurons, and suggest that this dependence is detectable only during a limited period of life.
| 22,769
|
[Treatment of childhood humeral fractures by wire fixation].
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Out of 526 upper limb fractures treated in the Pediatric Surgery Department of the Péterfy Sándor Hospital between 1970-1975, 63 patients were operated on. (11.9%). Fractures in childhood are generally treated by closed methods because healing of the growing bone is favourable. If it is reasonable, fractures of the forearm bones are successfully treated by means of intramedullary wire fixation, fractures of the elbow by means of transfixation. No septic complication occured following operation. Growth disturbancies were not observed in the affected bones after the operative intervention in the course of 1 to 5 years. On this ground the author recommends the adaptational "minimal" osteosynthesis in the treatment of fractures in infancy, if closed methods do not promise optimal results.
| 22,785
|
Physicians, physicians' assistants, and the social characteristics of patients in southern Appalachia.
|
A focus on health care delivery systems and the emergence of New Health Practitioners, particularly Physicians' Assistants (PAs), represents one of the more significant nonbiomedical developments in American medicine since World War II. Much discussion about PAs revolves around the kinds of illnesses they are qualified to treat which then permits physicians to concentrate on patients with other types of illnesses. Ignored in this focus on illness characteristics is the possibility that physicians and PAs may treat patients with different social characteristics. That issue is the topic of this paper. Differences between the status characteristics of physician and PA patients are reported for a rural community where PAs and physicians work side by side in the same offices. The relationships observed in this rural community suggest that the higher a patient's socioeconomic status, the more likely (s)he is to be treated by the physician.
| 22,793
|
The distribution of physician extenders.
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As part of the Medicare Physician Extender Reimbursement Study, a mail survey was conducted of 5,572 physician extenders (PEs) to identify potential study participants. Analysis of survey results indicates that PEs are distributed disproportionately more often than physicians to primary care practices and to rural low income areas. However, there are substantial differences among types of PEs with regard to practice location and practice arrangement. The relationship between these findings and the distribution of other medical manpower and innovations is then discussed.
| 22,794
|
Biochemical properties of a penicillinase from Escherichia coli carrying Rms 298.
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We obtained two R plasmids, i.e., Rms195 and Rms298, from a clinical isolate, E. coli GN5503. Penicillin beta-lactamase (PCase) was extracted from ML1410 Rms195+ and Rms298+, and was purified by chromatography. Rms195 PCase was identical to the type I PCase mediated by R-TEM, RI and Rms212. The isoelectric point of Rms298 PCase was 5.9 and its molecular weight was 21,000 +/- 1,000. The substrate profile and physiochemical properties indicate that Rms298 PCase belongs to the type IV PCase mediated by Rms139 isolated from Pseudomonas aeruginosa.
| 22,803
|
The use of microelectrodes for measurement of local H+ activity in the cortical subarachnoidal space of cats.
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pH microelectrodes with pointed tip (Hinke-type) were constructed for the continuous measurement of the local pH in the perivascular space of pial arteries in the feline cerebral cortex. The sensitive tip had a length of 20-60 mu and a base diameter of 10-25 mu. As reference electrode, a micropipette (tip diameter 2 mu), filled with 150 mM KCl was used. Calibration curves were linear and showed a sensitivity of 54.5-57.5 mV/pH unit at 38 degrees C. Advantages of such electrodes are the easy penetration of the subarachnoid membrane, the long life span, the quick response, and a minimal drift. The electrodes were tested in vivo during hyper- and hypoventilation and during local perivascular injection of mock spinal fluid at varying pH. A close correlation was observed between the change in perivascular pH and the corresponding change in pial arterial diameter.
| 22,841
|
Dose-dependent depression of cardiac function and metabolism by inhalation anesthetics in chronically instrumented dogs.
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Halothane, methoxyflurane, and enflurane produce dose-dependent depression in ventricular function in the dog. Myocardial blood flow and oxygen consumption are decreased accordingly without evidence of myocardial tissue hypoxia. Low-dose fluoxene does not depress the heart, while there is less depression with high-dose fluroxene than with the other anesthetics. In spite of this depression, myocardial blood flow was unchanged, and the decreased oxygen consumption during high-dose fluroxene was a result of decreased oxygen extraction by the heart. Sympathetic nervous system stimulation produced by fluroxene anesthesia is probably responsible for these effects, but further work is necessary for confirmation of this hypothesis.
| 22,904
|
PH and the effect of fluoride and zinc on protein and collagen biosynthesis in rabbit dental pulp in vitro.
|
The effect of pH in the range 6.6-8.2 on the incorporation of 14C-proline into the rabbit dental pulp incubated in vitro has been studied. The amount of label in the cold TCA-soluble pool, total protein, and hydroxyproline (i.e. collagen) of the pulp tissue increased linearly with pH in all three fractions. A similar increase was found in the amount of labeled total protein and collagen recovered from the incubation medium. The results indicated that the uptake of 14C-proline into the TCA-soluble pool was the pH-sensitive step, whereas the incorporation into protein, formation of hydroxyproline, and the release of labeled macromolecules into the medium were not affected to any measurable degree by the ambient pH. In this system, zinc (60 micrometer) had less effect on the incorporation of 14C-proline into the different fractions of the pulp tissue at pH 6.6 as compared with pH 7.4, whereas with fluoride (1.3 mM) an increased inhibition of the uptake of 14C-proline into the TCA-soluble pool and the incorporation into total protein was found upon lowering the pH to 6.8. The inhibitory effect of zinc and fluoride on the release of labeled total protein and collagen into the incubation medium was not affected when the pH was lowered.
| 22,925
|
Characterization of the beta-adrenergic receptors in the lower urinary tract of the cat.
|
The corpus-fundus and the outlet region of the urinary bladder of the cat was studied in vitro to characterize the beta-adrenergic receptors. In the corpus-fundus only beta1-receptors were found in contrast to the outlet region where the beta-receptors had both beta1-and beta2-characteristics.
| 22,927
|
Secretion of various antimicrobial substances in dogs with experimental bacterial prostatitis.
|
Bacterial prostatitis in dogs was induced by injection of an E. coli 06 suspension into a branch of the prostatic artery. Three to six days later, secretion from the inflamed glands was obtained by pilocarpine stimulation and the concentrations of trimethoprim, sulphamethoxazole, erythromycin, doxycycline and ampicillin were measured during constant infusion of these drugs. In the prostatic secretion, only the concentrations of the lipid soluble substances trimethoprim and erythromycin exceeded the corresponding plasma levels. These two substances may therefore be of value in the treatment of bacterial prostatitis.
| 22,949
|
[Thermostable basic proteinase inhibitors from potatoes. Isolation and characterization (author's transl)].
|
Four basic proteinase inhibitors were isolated from potato tubers (var. Maritta) by ammonium sulfate precipitation, heat treatment, chromatography on CM-cellulose and preparative polyacrylamide gel electrophoresis. Their isoelectric points are in the pH range 9.2--9.8. The molecular weights, as estimated by Sephadex gel filtration, were 8500 for inhibitor K 1 and 22000 for the inhibitors K3, K4, and K6. Differences in inhibitors regarding amino acid composition and specific activity against six different proteinases are discussed. Comparisons with previously described inhibitors are given. A correlation between high cystine content and thermostability of the inhibitor proteins is indicated.
| 22,962
|
Some effects of sugar-flavored acid beverages on the biochemistry of human whole saliva and dental plaque.
|
An investigation was made of the effects on some biochemical characteristics of human whole saliva and dental plaque resulting from the daily consumption of three commercial, acid-containing beverages. The beverages tested were a cola beverage ("Coca-Cola"), a carbonated orange drink ("Jaffa") and single strength orange juice. Each of the three test beverages as well as non-fluoridated tap water as a control, were consumed during four two-week periods. The test group consisted of 39 dental students. The mean consumption frequency lay in the range from 5.3 to 5.7 times per day. Orange juice was found to stimulate the salivary secretion rate most. All test drinks decreased the salivary pH immediately after consumption, but the pH did not generally drotase-like activity in oral fluid. Changes were observed in calcium, phosphate and fluoride concentrations in oral fluid samples, but these were due to variations in salivary secretion rate. A significant decrease in redox potentials of whole saliva was, however, observed after consumption of the drinks. The present results indicate that in healthy persons with normal saliva flow rate and buffer capacity the moderate consumption of acidic beverages failed to induce any remarkable caries-promoting changes in oral cavity. However, in persons with low salivary flow rate erosion may be a consequence of regular consumption.
| 22,979
|
The effect of adrenaline on acetylcholine synthesis after blockade of alpha- and beta-adrenergic receptors in vitro.
|
The aim of the present work was to explain the mechanism of the stimulating effect of adrenaline (A) on acetylcholine (ACh) synthesis. This action is exerted most probably through the beta- adrenergic receptors, since propranolol and oxprenolol inhibit the stimulating effect of adrenaline on acetylcholine synthesis in the rat cerebral cortex in vitro. Dihydroergotamine does not show such effect. Practolol and phentolamine decrease the spontaneous synthesis of ACh in concentration several times lower than that inhibiting the ACh synthesis stimulated by adrenaline. It is suggested that adrenaline-induced stimulation of ACh synthesis in the rat cerebral cortex is not due to cyclic AMP, because noradrenaline (NA) does not increase ACh synthesis either in vivo or in vitro, although it activates the adenyl cyclase. NA on the other hand activates ACh synthesis in the calcium-free medium, which inhibits activating effect of NA on adenyl cyclase. Moreover it was found that cyclic AMP depresses ACh synthesis in the rat cerebral cortex in vitro.
| 22,984
|
A cat head model with isolated perfusion by the animal's own blood.
|
A model consisting of a cat head perfused in isolation with the animal's own blood is described. The use of endogenous blood allows the organ to function under physiological conditions for several hours. The blood is taken from the abdominal aorta of the anaesthetized animal and passed to the carotid arteries via an extracorporeal circulation system. The perfusion pressure can be varied at will and is regulated electronically. The volume of blood in the extracorporeal circulation system is only 6 ml. The tests performed on this model were designed to study the behaviour of the cortical EEG and the cortical micro flow. Neither of these parameters underwent any change after institution of the artificial perfusion, and the blood gases also remained fairly stable. The model is suitable for studying both physiological and pharmacological problems.
| 23,001
|
[A comparative study of the course of aged patients with hip surgery].
|
On an orthopedic surgical unit we studied the course of patients aged over 70 years who had undergone surgical operation on the hip in 1974 and 1975. Distinguishing the pre-opérative, per-operative and post-operative stages, we used firstly, the distribution according to age and sex, the past history, the laboratory findings, the type of operation and the type of anesthetic. Then, we carried out a comparative analysis in relation to the past history, the post-operative complications and the deaths.
| 23,048
|
[Metabolic and pharmacologic interactions on the bronchial tonus].
|
After reminding data concerning the part played by the as a rule antagonist cAMP system in moticity of the smooth muscle fibers in general and of the bronchial fibers in particular, the authors study the different types of interaction on bronchial muscular fibers which have been discribed. It is concerning the adrenergic fibers that the experimental and clinical data are prevalent (role of bronchial alpha- and beta2- receptors) and the authors point especially to their own studies performed since 1964 concerning the alpha1- -bronchoconstrictive component and progressive auto-inhibition of the bronchial beta2- receptors. But autacoids (serotonin, bradykinin, histamine and prostaglandines) and with the stimulating or inhibiting agents of the beta2 -receptors also begin to be recognized.
| 23,051
|
[E. coli penicillin amidase. Physico-chemical properties of the enzyme covalently bound to the 2-(3'-amino-4'-methoxyphenyl)-sulfonylethyl ester of cellulose].
|
The effect of the procedure of the enzyme binding with the carrier on the properties of the heterogenous catalyst obtained by covalent binding of penicillinamidase (PA) with cellulose 2-(3'-amino-4'-methoxyphenyl)-sulphonylethyl ether by means of the bifunctional reagent, i.e. glutaric aldehyde was studied. It was shown that the amount of the bound enzyme increased with a rise in the amount of the enzyme taken for the binding, while the binding efficiency characterizing the part of the active enzyme in the total amount of the bound PA decreased practically 2 times. The use of the enzyme preparations with different purify levels for the binding provided differentiation of the effects resulting in the activity loss on immobilization. In other words it provided separate estimation of the inactivation effect of the matrix and the immobilization procedure, as well as the interaction of the enzyme molecules with each other and other protein molecules.
| 23,067
|
Cerebrospinal fluid acid-base status and lactate and pyruvate concentrations after short (less than 30 minutes) first febrile convulsions in children.
|
Twenty-nine infants and children with short (less than 30 minutes) first febrile convulsions were studied between 3 and 22 hours after convulsive episodes. Arterial and CSF acid-base variables, lactate and pyruvate concentrations, and lactate/pyruvate ratios were measured. Biochemical signs of cerebral hypoxia were found in only 2 patients, one of whom had short, repeated convulsions. Our findings indicate that hypoxic damage is unlikely to result from a short-duration febrile convulsion.
| 23,077
|
Resolution and reconstitution of Rhodospirillum rubrum pyridine dinucleotide transhydrogenase. II. Solubilization of the membrane-bound component.
|
The Rhodospirillum rubrum pyridine dinucleotide transhydrogenase system is comprised of a membrane-bound component and an easily dissociable soluble factor. Active transhydrogenase complex was solubilized by extraction of chromatophores with lysolecithin. The membrane component was also extracted from membranes depleted of soluble factor. The solubilized membrane component reconstituted transhydrogenase activity upon addition of soluble factor. Various other ionic and non-ionic detergents, including Triton X-100, Lubrol WX, deoxycholate, and digitonin, were ineffectual for solubilization and/or inhibited the enzyme at higher concentrations. The solubilized membrane component was significantly less thermal stable than the membrane-bound component. None of the pyridine dinucleotide substrate affected the thermostability of the solubilized membrane-bound component, whereas NADP+ and NADPH afforded protection to membrane-bound component. NADPH stimulated trypsin inactivation of membrane-bound component to a greater extent that NADP+, but inactivation of solubilized membrane component was stimulated to the same extent by both pyridine dinucleotides. The solubilized membrane component appears to have a slightly higher affinity for soluble factor than does the membrane-bound component.
| 23,085
|
Electron-paramagnetic-resonance studies of leghaemoglobins from soya-bean and cowpea root nodules. Identification of nitrosyl-leghaemoglobin in crude leghaemoglobin preparations.
|
1. Leghaemoglobins from soya-bean (Glycine max) and cowpea (Vigna unguiculata) root nodules were purified by chromatography on DEAE-cellulose phosphate columns at pH8.0 and pH5.8, to avoid the relatively low pH (5.2) commonly used to purify these proteins. 2. E.p.r. (electron-paramagnetic-resonance) spectra of the fluoride, azide, hydroxide and cyanide complexes of these ferric leghaemoglobins were very similar to the spectra of the corresponding myoglobin derivatives, indicating that the immediate environment of the iron in leghaemoglobin and myoglobin is similar, an imidazole moiety of histidine being the proximal ligand to the haem iron [cf. Appleby, Blumberg, Peisach, Wittenberg & Wittenberg (1976) J. Biol. Chem.251, 6090-6096]. 3. E.p.r. spectra of the acid-metleghaemoglobins showed prominent high-spin features very near g=6 and g=2 and, unlike myoglobin, small low-spin absorptions near g=2.26, 2.72 and 3.14. The width of the g=6 absorption derivative at 10-20K was about 4-4.5mT, similar to the value for acid-methaemoglobin. In contrast, a recently published (Appleby et al., 1976) spectrum of acid-metleghaemoglobin a had less high-spin character and a much broader absorption derivative around g=6. 4. E.p.r. spectra of ferric leghaemoglobin nicotinate and imidazole complexes suggest that the low-spin absorption near g=3.14 can be attributed to a trace of ferric leghaemoglobin nicotinate, and those near g=2.26 and 2.72 are from an endogenous dihistidyl haemichrome. 5. A large e.p.r. signal at g=2 in all samples of crude leghaemoglobin was shown to be from nitrosyl-leghaemoglobin. A soya-bean sample contained 27+/-3% of the latter. A previously unidentified form of soya-bean ferrous leghaemoglobin a was shown to be its nitrosyl derivative. If this is not an artifact, and occurs in the root nodule, the nitrosyl radical may interfere with the function of leghaemoglobin.
| 23,110
|
Enzymes of the gamma-glutamyl cycle in 'aging' WI-38 fibroblasts and in HeLa S3 cells.
|
gamma-Glutamyltransferase ((5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2) activity of WI-38 fibroblasts decreased only slightly in relation to a constant amount of cell-associated protein as the cells were carried in culture serially from middle to late passage numbers leading toward senescence, e.g., from population doubling level 27 through 41. Also, when the enzyme activity was expressed on the basis of a unit number of cells or unit amount of DNA, little change occurred over that range of PDLs. As the culture approached 'phase-out', the transferase activity rose sharply regardless of how the activity was expressed. The possibility is considered that the large increase in activity could be a reflection of a significant increase in size of cells and therefore changes in the membranes where the transferase is located. The occurrence of other enzymes of the 'gamma-glutamyl cycle' in WI-38 and HeLa S3 cells also was demonstrated. These included gamma-glutamylcyclotransferase ((gamma-L-glutamyl)-L-amino-acid gamma-glutamyltransferase (cyclizing), EC 2.3.2.4) and 5-oxoprolinase, whose activities showed no large increase comparable to that of the gamma-glutamyltransferase, as the culture approached 'phase-out'.
| 23,165
|
Tyrosine aminotransferase from chick liver. Heat activation and cold inactivation of the enzyme.
|
The reversible heat activation and cold inactivation of tyrosine aminotransferase (L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) of chick liver were investigated. When the enzyme obtained by gel filtration was preincubated at 37 degrees C for 10 min with 50 micrometer pyridoxal 5'-phosphate (pyridoxal-5'-P), a 7-fold increase in enzyme activity was detected. When the preincubated enzyme was cooled to 0 degrees C, it lost its activity. Furthermore, the dramatic cyclical changes in enzyme activity occurred by sequential heating at 37 degrees C and cooling to 0 degrees C of the enzyme, in the presence of pyridoxal-5'-P, over shorter periods of time without loss of enzyme activity. However, when alpha-ketoglutarate was added to the enzyme during cold exposure, no further decrease in activity was observed. This protective effect was seen at a concentration of 5 muM.
| 23,167
|
Synthesis of acyl phosphatidylglycerol from phosphatidylglycerol in Escherichia coli K-12. Evidence for the participation of detergent-resistant phospholipase A and heat-labile membrane-bound factor(s).
|
The conversion of phosphatidylglycerol to acyl phosphatidylglycerol by extracts of Escherichia coli K-12 strains was examined under various conditions. The maximum rate of conversion was observed at pH 7.2 in the presence of 50% (v/v) diethyl ether and 10 mM CaCl2. This conversion was found to involve two sequential reactions: (1) The formation of 2-acyl glycerophosphoglycerol and 2-acyl glycerophosphoethanolamine from phosphatidylglycerol and phosphatidylethanolamine, respectively, by detergent-resistant phospholipase A in the presence of Ca2+ and (2) transfer of the acyl group of 2-acyl lysophospholipid to phosphatidylglycerol by a heat-labile factor(s) in the presence of diethyl ether. Neither fatty, acid acyl-CoA nor 1-acyl lysophospholipid could act as an acyl donor for phosphatidylglycerol. The heat-labile factor(s) was found in both the inner membrane and supernatant fractions.
| 23,168
|
The effect of temperature on the motility and viability of sperm.
|
In specimens of semen kept at 37 degrees C sperm lose their motility and viability. If kept at 4 degrees C they retain their viability but lose their motility from so-called thermal shock. The best temperature to keep semen in order to preserve sperm motility is 20 degrees C. Loss of motility at 37 degrees C is not entirely prevented by prevention of bacterial contamination with antibiotics.
| 23,196
|
Effect of monoamine receptor agonists and antagonists on cyclic AMP accumulation in human cerebral cortex slices.
|
In human cerebral cortex slices noradrenaline, isoproterenol (a beta-adrenergic agonist), dopamine, apomorphine (a dopaminergic agonist), and serotonin stimulated cyclic AMP formation: noradrenaline greater than or equal to isoproterenol greater than dopamine = apomorphine = serotonin. Clonidine (and alpha-adrenergic agonist) was ineffective in stimulating cyclic AMP formation in temporal cortex slices. The stimulatory effect of noradrenaline and isoproterenol was blocked by propranolol (a beta-adrenergic blocker) but not by phentolamine (an alpha-adrenergic blocker). Pimozide (a selective dopaminergic antagonist) inhibited the increase of cyclic AMP formation induced by dopamine or apomorphine but not that induced by noradrenaline, isoproterenol, or serotonin. Neither propranolol or phentolamine had any effect on dopamine- or serotonin-stimulated cyclic AMP formation. Chlorpromazine blocked the increase of cyclic AMP formation induced by noradrenaline, dopamine or serotonin, while cyproheptadine, a putative central serotonergic antagonist, was ineffective. These observations suggest that there may be at least two monoamine-sensitive adenylate cyclases in human cerebral cortex which have the characteristics of a beta-adrenergic and a dopaminergic receptor, respectively, and also possibly a serotonergic receptor.
| 23,211
|
Endotoxemia and large intestinal blood flow in subhuman primates.
|
The hemodynamic effects of Escherichia coli endotoxin (LD80) were measured in the large intestine of anesthetized Rhesus monkeys to determine whether this organ contributes to the pathogenesis of experimental shock. Inferior mesenteric arterial blood flow (IMF) was measured with an electromagnetic flowmeter. Pressures within the aorta (AP) and portal vein (PP) were recorded. Distribution of colon blood flow was measured with radioactive microspheres: Ce, Sr, and Cr were injected into the left heart. Reference blood samples were obtained from a femoral artery. Mean control IMF was 22.9 +/- 2.2 (SE) ml/min. Aortic pressure was 113 +/- 11 mm Hg, and PP was 6 +/- 1 mm Hg. Arterial blood pH was 7.43 +/- 0.02; pO2 and pCO2 were 93.4 and 37.1 mm Hg, respectively. All parameters were measured at hourly intervals for 4 hr. Neither IMF nor its distribution within the colon changed during the entire observation period. Aortic pressure fell to a low of 60 +/- 6 mm Hg (p less than 0.02) at 3 hr; PP, pO2 and pCO2 were unchanged by endotoxin. Arterial blood pH fell to 7.315 +/- 0.020 at 4 hr (p less than 0.01). These observations indicate that the colon is not a "target organ" of endotoxic shock in subhuman primates, despite considerable hypotension and metabolic disturbances subsequent to near lethal endotoxemia.
| 23,223
|
Age-dependent renal accumulation of cephaloridine in the rabbit.
|
The accumulation of cephaloridine in the renal cortex of the rabbit was studied in vitro and in vivo in rabbits of various ages. The cortical concentration of cephaloridine, the cortex/serum ratio, and the slice/medium ratio determined by incubation of cortical slices in cephaloridine-containing media rose from birth to adult levels at approximately 1 month of age. Pretreatment with procaine penicillin G stimulated the ability to accumulate cephaloridine in vitro and in vivo. The data indicate that the lack of susceptibility of immature rabbits to cephaloridine nephrotoxicity is due to the lack of development of the anionic transport system which is apparently necessary to achieve the high cortical concentrations of cephaloridine that result in renal injury.
| 23,280
|
Haemodynamic response to graded exercise during chronic beta-adrenergic blockade with bunitrolol, an agent with intrinsic sympathomimetic activity.
|
The effect of chronic beta blockade on the haemodynamic response to graded exercise was studied in 18 hypertensive patients treated with bunitrolol, which has partial agonist activity. The patients first received a placebo for 5 to 12 days, then bunitrolol 30 mg daily for one week and subsequently the dose was doubled weekly as necessary up to 240 mg daily. At rest haemodynamic changes after beta blockade were only minor; heart rate decreased by 8% and no significant change was observed in stroke index, cardiac index, (a-v)O2 difference and VO2. The hypotensive effect was not significant and no significant change in mean pulmonary arterial and wedge pressure was observed. Maximal exercise capacity remained unchanged, because of haemodynamic responses. The maximal exercise heart rate was reduced by 25% during beta blockade, which was compensated by a 34% elevation in stroke index, whereas maximal cardiac index and (a-v)O2 difference remained unchanged. There was no consistent change in mean pulmonary artery pressure during maximal exercise, but the mean brachial artery pressure fell by 12%.
| 23,295
|
[Precancerous lesions in the gastrointestinal tract].
|
In the large intestine, the pathologist has to differentiate between multiple polyps and polyposis (more than 100 polyps), further between adenomatosis (coli) and non-neoplastic (tumorlike) polyposis. Without prophylactic colectomy, in about 80% of adenomatosis patients an evolution of cancer is observed. Patients with extensive or total ulcerative colitis and a long history have an increased risk for developing carcinoma. Precancerous dysplasia can be demonstrated in rectoscopic and/or colonoscopic biopsies. Cancers complicating adenomatosis or ulcerative colitis account for only a very small proportion of large bowel carcinoma. The "adenoma-cancer sequence" is of greater importance. Colorectal polyps should be removed endoscopically whenever possible. Most gastric polyps are non-neoplastic and have no carcinomatous potential. The true adenoma and the so-called borderline lesion only can be considered as precursor of the gastric carcinoma.
| 23,348
|
[Pityriasis versicolor in Greece and its predisposition factors].
|
The age and seasonal incidence of 2610 patients with pityriasis versicolor in Greece were studied. Determination of the pH of Na and K ions of the sweat and the microbiol flora of the skin of pityriasis versicolor patients was undertaken. Besides these the effectiveness of a 1% selenium disulfid suspension was tested. The results indicate that the age groups of 20-29 and 30-30 years are mostly affected by the disease. A high incidence of the skin manifestation was noted during the summer and fall months. A difference of the pH of the sweat between pityriasis versicolor and healthy controls was observed, but no difference was found in the Na and K ions of the sweat among these two groups. Neither did the microbial flora from the skin lesions of patients and from corresponding sites of controls show any difference. The high relapse in this experiment indicates the relative ineffectiveness of selenium disulfid preparations when used as a 1% suspension in the treatment of pityriasis versicolor.
| 23,362
|
Preparation of peroxisomes from carp liver by zonal rotor density gradient centrifugation.
|
Peroxisomes from carp liver can be separated by isopycnic density gradient centrifugation in sucrose. Without reaching complete sedimentation equilibrium, the purification by this method is quite successful. There is a 40-fold enrichment of catalase, the peroxisomal marker, with a total yield of 27%. No pretreatment of animals is necessary for separation from lysosomes, which, besides high fragility, show lower buoyant densities than peroxisomes. The enzyme content of carp liver peroxisomes is similar to that of rat liver, with the exception of alpha-glycerophosphate dehydrogenase, which in this tissue is a completely soluble cytoplasmic enzyme. Total activities are much lower than in the rat, for the characteristic peroxisomal oxidases the difference being in the range of one order of magnitude.
| 23,363
|
Determination of the metabolites of bezitramide in urine. I. Acidic metabolite.
|
Two methylation methods are compared in relation to the determination of low levels (less than microgram/ml) of the acidic metabolite of bezitramide in human urine. It was necessary to use alkali flame ionisation detector, which specifically detects nitrogen-containing compounds. Several difficulties associated with the use of this detector are described.
| 23,390
|
On the effects of divalent cations and ethylene glycol-bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetate on action potential duration in frog heart.
|
Resting and action potentials were recorded from superfused strips of frog ventricle. Reducing the bathing calcium concentration ([Ca2+]0) with or without ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA) prolongs the action potential (AP). The change in the duration of the AP extends over many minutes, but is rapidly reversed by restoring calcium ions. Other changes (e.g., in resting potential and overshoot) are, however, only more slowly reversed. Reducing [Ca2+]0 with 0.2, 2, or 5 mM EGTA produces progressively greater prolongation of AP; maximum values were well in excess of 1 min. This prolongation can be reversed by other divalent cations in EGTA (Mg2+, Sr2+) or Ca-free (Mn2+) solutions, or by acetylcholine. Barium ions increase AP duration in keeping with their known effect on potassium conductance. D600, which blocks the slow inward current in cardiac muscle, is without effect on the action potentials recorded in EGTA solutions, or on the time course and extent of the recovery to normal duration upon restoring calcium ions. It is concluded that divalent cations exert an influence on membrane potassium conductance extracellularly in frog heart. The cell membrane does not become excessively "leaky" in EGTA solutions.
| 23,408
|
Study of the structural requirements for dopa potentiation and oxotremorine antagonism by L-prolyl-L-leucylglycinamide.
|
A number of analogs of the tripeptide L-prolyly-L-leucylglycinamide (1) were synthesized and evaluated in the Dopa potentiation and oxotremorine antagonism tests. The replacement of the glycinamide residue with either the glycine methylamide, glycine, aminoacetonitrile, amino-2-propanone, semicarbazide, or beta-alaninamide residues resulted in a loss of activity in both tests. A 1:1 mixture of L-prolyl-L-leucyl-(-)-thiazolidine-2-carboxamide (8) and L-prolyl-L-leucyl-(+)-thiazolidine-2-carboxamide (9) showed marked activity in the Dopa potentiation test but was unable to antagonize the tremors induced by oxotremorine. L-Prolyl-L-leucyl-L-prolinamide (11), on the other hand, was active in the oxotremorine antagonism test but inactive in the Dopa potentiation test. The replacement of the pyrrolidine ring of 1 with either a thiazolidine or cyclopentane ring system caused a loss of activity. The cyclopentanecarboxylic acid analogue 13, however, was found to have moderate activity in the serotonin potentiation test.
| 23,433
|
The ability of smooth and rough strains of Streptococcus pneumoniae to activate human complement by the alternative pathway.
|
Three capsulate pneumococcal strains of serotypes 1, 2 ans 3, and one non-capsulate strain of serotype 47, were found to activate human complement by the alternative pathway to a similar extent over the concentration range examined. Nevertheless, the capsulate strains, in contrast to the non-capsulate, are known to require complement attachment for phagocytosis and it is therefore postulated that the toxic by-products released cause the wave of oedema characteristic of pneumococcal lobar pneumonia.
| 23,434
|
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