Activation and desensitization of platelets by platelet-activating factor (PAF) derived from IgE-sensitized basophils. I. Characteristics of the secretory response. The secretion of vasoactive amines from rabbit platelets induced by the platelet-activating factor (PAF) derived from IgE-sensitized rabbit basophils, was examined. The secretion required calcium has previously been shown to be noncytotoxic and was optimal in both rate and extent at 37 degrees C and pH 7.2. Different temperature-sensitive steps were rate limiting for secretion above or below 20 degrees C. The rate of secretion was dependent upon the concentration of PAF and also of platelets. Maximal rates were observed with relatively low concentrations of platelets (2.5 X 10(8)/ml), sharply contrasting with other platelet stimuli such as C3 or thrombin. The extent of secretion was dependent upon PAF concentration until a maximum of 50 or 60% of the serotonin was released and then declined with increasing amounts of PAF. This was interpreted to result from the platelets becoming desensitized to the PAF, a process that shuts off the secretion. Such a desensitization was demonstrated and was shown to be stimulus specific, i.e., other stimuli could still induce secretion from PAF-desensitized platelets. PAF extracted with ethanol from the albumin to which it is usually bound during preparation, exhibited similar characteristics, except that secretion of up to 90% of the serotonin was induced. The extracted PAF thus seemed less able to induce the desensitization. Its use did provide important evidence that populations of rabbit platelets are relatively homogenous in their ability to respond to PAF.


Activation of platelets by platelet-activating factor (PAF) derived from IgE-sensitized basophils. II. The role of serine proteases, cyclic nucleotides, and contractile elements in PAF-induced secretion. Secretion of serotonin from platelets induced by platelet-activating factor (PAF) derived from antigen-stimulated, IgE-sensitized rabbit basophils was studied to further characterize the biochemical requirements. Inhibition of secretion with diisopropylphosphofluoridate (DFP) was observed if the DFP was present during the reaction, but not if platelets or PAF were pretreated with the inhibitor. This suggested a role for an activatable serine protease in the secretion. Supporting evidence came from the observation that other protease inhibitors and a variety of low molecular weight amino acid esters were also inhibitory. TAMe was most effective, and AGLMe and LeuMe were inactive, indicating a specificity for different esters. Secretion was reduced by agents that increased intracellular cyclic AMP (cAMP), but enhanced by alpha-adrenergic stimulation, which reduced the levels of cAMP. Concurrent with PAF-induced secretion, a reduction in cAMP levels was observed. No effect of cyclic GMP or cholinergic stimulation was found. Secretion was inhibited by colchicine and enhanced by cytochalasin B, suggesting a role for microfilaments and microtubules. The effects of these three systems on PAF-induced secretion indicate the basic uniformity of the secretory process in platelets (and other cells) whatever the stimulus. The uniqueness of the reaction apparently lies in the stimulus-receptor interaction and the nature of the serine protease which is activated.


Acid hydrolases in leukocytes and platelets of normal subjects and in patients with Gaucher's and Fabry's disease. Lymphocytes, monocytes, neutrophilic granulocytes and platelets were each separated to greater than 95% purity from six normal subjects, three patients with Gaucher's disease, two heterozygotes for Gaucher's disease, and one patient with Fabry's disease. Activities of the following acid hydrolases were determined: "acid" (pH 4.0) beta-glucosidase, pH 5.0 beta-glucosidase, alpha-galactosidase, alpha-arabinosidase, alpha-mannosidase, alpha-glucosidase, beta-glucuronidase, beta-galactosidase, beta-hexosaminidase, and acid phosphatase. Enzymatic activity varied greatly with cell type and the enzyme being measured; the importance of assaying pure preparations especially for heterozygote detection is emphasized. Gaucher's disease patients' cells were found to be deficient in the pH 4.0 acid beta-glucosidase, variable in the pH 5.0 beta-glucosidase, and normal in all other acid hydrolases tested, including acid phosphatase, the activity of which is known to be elevated in plasma. Blood cells of a patient with Fabry's disease were deficient in alpha-galactosidase and normal in all other acid hydrolases tested.


Regulation of the oxidative NADP-enzyme tissue levels in Drosophila melanogaster. I. Modulation by dietary carbohydrate and lipid. Wild-type third instar larvae of Drosophilia melanogaster fed a casein-sucrose synthetic diet supplemented with phosphatidylcholine (4 mg/ml) possessed 33% more tissue lipid and a modified fatty acid profile compared to larvae fed a fat free-sucrose diet. The rates of lipid synthesis and pentose shunt activity were 2.1 and 2.2 times greater respectively in larvae fed the fat free-sucrose diet than in fat-sucrose fed animals. The tissue concentrations of acetyl-CoA and acyl-CoA were 80 and 61% higher respectively, CoA 49% lower, and the NADPH/NADP+ ratio greater in fat-sucrose fed larvae than in larvae fed a fat free-sucrose diet. Thus, larvae effectively utilized dietary lipid for lipid synthesis and as a supplementary energy source to carbohydrate.


Analysis of acetate non-utilizing (acu) mutants in Aspergillus nidulans. Genetic analysis of 119 acetate non-utilizing (acu) mutants in Aspergillus nidulans revealed ten new loci affecting acetate metabolism in addition to the three previously recognized on the basis of resistance to fluoroacetate and acetate non-utilization. The enzyme lesions associated with mutations at seven of the acu loci are described. These are: facA (= acuA), acetyl-CoA synthase; acuD, isocitrate lyase; acuE, malate synthase; acuF, phosphoenolpyruvate carboxykinase; acuG, fructose 1,6-diphosphatase; acuK and acuM, malic enzyme. The acu loci have been mapped and are widely distributed over the genome of A. nidulans. Close linkage has only been found between acuA and acuD (less than 1% recombination). There is no evidence for any pleiotropic mutation in that region affecting the expression of both these genes. Poor induction of the enzymes of the glyoxylate cycle, isocitrate lyase and malate synthase in mutants lacking acetyl-CoA synthase, and also in the other two classes of fluoroacetate-resistant mutants, indicates that the inducer, acetate, may be metabolized to a true metabolic inducer, perhaps acetyl-CoA, to effect formation of the enzymes. There is no evidence of any other class of pleiotropic recessive acu mutations affecting the expression of the acuD and acuE genes, which are therefore thought to be subject to negative rather than positive control.


Predicting individual responses to drug treatment in schizophrenia: a test dose model. The literature and the findings from the Camarillo Schizophrenia Research Project reported in this paper indicate that a satisfactory method for predicting the response of an individual schizophrenic patient to antipsychotic drugs has yet to be devised. A test dose procedure is described which offers promise of a practical approach to selecting the most appropriate drug and dosage for a particular patient and tailoring blood concentrations to the needs of the individual case. Preliminary findings indicate that the test dose procedure is feasible; that detectable changes occur after a single test dose; and that measurements made during the test dose period may be predictive of eventual outcome. These findings are, of course, only a report of a preliminary pilot experiment, subject to important caveats about small number of cases, interpretation of large numbers of correlation coefficients, and need for cross-validation. Nevertheless, they are encouraging and suggest that the test dose approach has considerable potential for further research.


On the bimodality of the distribution of electrodermal orienting responses in schizophrenic patients. Data are presented from four of the author's studies on the electrodermal orienting responss which fail to confirm the findings of Gruzelier and Venables of a markedly bimodal distribution of ORs in schizophrenic populations. A review of the findings of other earlier studies, none of which confirm the bimodal hypothesis although some used patients taking phenothiazines, shows that differential effects of drugs, although probably an important factor, by itself cannot account entirely for the discrepancies in results. It is hypothesized that due to changes in hospital discharge policies, the groups of patients tested by Gruzelier and Venables, compared to those tested in earlier studies, were more heavily weighted with patients whose symptoms were resistant to phenothiazines. These patients may either have come from the extremes of the responsivity distribution or have atypical reactions to neuroleptic drugs.


Sudden hemorrhage in metastatic thyroid carcinoma of the brain during treatment with iodine-131. A patient with papillary--follicular carcinoma of the thyroid, with metastases to the lungs, skeleton, and brain was treated 5 weeks after thyroidectomy with 135 mCi of 131I. Although preliminary studies with 1 mCi had not shown any iodine uptake by the brain metastasis, this lesion showed intense concentration at the time of the larger therapeutic dose. Four days later, acute hemorrhage of the tumor occurred, requiring surgical removal. Although 131I therapy would seem an unlikely cause of acute necrosis and hemorrhage in these lesions, the association of therapeutic radioiodine and hemorrhage is interesting. Since recent reports suggest that brain metastasis may be somewhat more common than previously suspected, we suggest that brain imaging be included in the workup prior to radioiodine therapy of patients with advanced metastatic disease or neurologic symptoms.


Concentrations of bacteria in cerebrospinal fluid of patients with bacterial meningitis. Concentrations of bacteria in cerebrospinal fluid ranged from 4.5 X 10(3) to 3 X 10(8) colony-forming units/ml in 27 patients with bacterial meningitis before antibiotic therapy and from 4 X 10(1) to 1.4 X 10(6) CFU/ml in four patients after one to two days of antibiotic therapy. All patients with persistent positive cultures had pretreatment concentrations of 10(7) CFU/ml or greater. A significant association was observed between cerebrospinal fluid lactic acid dehydrogenase activity and concentrations of bacteria (p less than 0.01). Large inocula of Hemophilus influenzae type b (10(7)) increased the minimal inhibitory concentration for penicillin and ampicillin but not for chloramphenicol. The minimal inhibitory concentration of each of the three antibiotics increased when group B streptococci were assayed. These data indicate that persistence of a positive culture may be related to large initial concentrations of bacteria. The relative "resistance" in vitro of large inocula possibly contributes to this persistence. These observations are also consistent with the hypothesis that lactic acid dehydrogenase activity in cerebrospinal fluid is derived from bacteria.


Quantitative determination of resorcinol in presence of phenol. A simple and accurate method for the quantitative determination of resorcinol in the presence of phenol is reported. The method is based on the formation of indophenol by reacting resorcinol with 2, 6-dibromoquinone-4-chlorimide. The concentration of indophenol can be measured spectrophotometrically. This method is recommended for the determination of resorcinol in resorcinol-phenol-boric acid solution and carbol-fuchsin solution. The decomposition products of resorcinol and phenol, e.g., colored quinones, do not interfere with the assay procedure.


Oil-water distribution of p-alkylpyridines. The distribution of a homologous series of p-alkylpyridines between water and six organic solvents with varying degrees of polarity was investigated. The distribution coefficients were considered as reflections of the strength of net interactions involved in the solvents. The order was chloroform greater than octanol greater than carbon tetrachloride greater than butyl ether greater than hexadecane greater than octane. The effect of the methylene group upon the distribution coefficients differed little among the six solvents. The relative constancy was attributed to the predominance of the dispersion forces in the incremental effect.


Neurogenic influences of bilateral adrenalectomy on monoamine oxidase. Bilateral adrenalectomy (10 days) increased the monoamine oxidase activity of the rat heart, vas deferens, spleen, superior cervical ganglion, and hypothalamus but not that of the rest of the brain, kidney, and liver. Experiments were made to determine whether the increased activity was due to neurogenic influences and whether the enhanced activity of monoamine oxidase was intra- or extraneuronally located. Ganglionic blockade with chlorisondamine failed to alter the rise in cardiac monoamine oxidase. Likewise, superior cervical ganglion monoamine oxidase was unaffected by surgical denervation. 6-Hydroxydopamine abolished the increase in monoamine oxidase activity of the vas deferens, spleen, and superior cervical ganglion but failed to alter that of the kidney, hypothalamus, and the rest of the brain. Cardiac monoamine oxidase was reduced markedly by 6-hydroxydopamine, but the remaining activity was still significantly elevated over the respective control values. The data suggest that the increase in organ monoamine oxidase is predominantly of neuronal origin and that this increase is not due to transsynaptic induction.


Binding study of tetracyclines to human serum albumin using difference spectrophotometry. The binding of several tetracyclines to human serum albumin was studied using difference spectrophotometry and a spectrophotometric probe, 2-(4'-hydroxybenzeneazo)benzoic acid. Difference spectra observed for the interaction between the probe and human serum albumin were similar to probe-bovine serum albumin spectra but were less intense for a given concentration of probe and did not reach saturation as quickly. Difference spectra for the tetracyclines were dependent on the characteristics of the ring substituents. More hydrophobic substituents on the D and C rings tended to give more intense difference spectra, but charge-transfer complexing may also have been involved since methacycline with a methylene group in the 6-position showed the most intense spectra of the compounds studied. Solvent perturbation, pH, and urea studies tended to confirm that something other than hydrophobic binding of the tetracyclines was involved. Drug-probe displacement studies showed that methacycline gave the greatest probe displacement followed by doxycycline, chlortetracycline, oxytetracycline, and tetracycline. This order of displacement of the anionic probe indicates that both hydrophobic and charge-transfer binding are involved. Experiments with calcium ion and ethylenediaminetetraacetic acid showed that the difference spectra obtained with the tetracyclines and human serum albumin were not the result of metallic bridge-chelate formation.


Fluorescence of hydralazine in concentrated sulfuric acid. Hydralazine shows intense fluorescence at 353 nm in concentrated sulfuric acid when excited at 320 nm. This fluorescence can be utilized for the quantitative analysis of the drug in dosage forms.


The antiarrhythmic and cardiovascular properties of 1-dimethyl isopropylamino-3-(2-phenylphenoxy)-propan-2-ol chloride, UM-424. The quarternary ammonium compound, UM-424 [1-dimethyl isopropylamino-3-(2-phenylphenoxy)-propan-2-ol chloride], was evaluated for its antiarrhythmic and hemodynamic effects. UM-424 converted ouabain-induced ventricular tachycardia in the anesthetized dog when administered in an average dose of 4.6 mg/kg i.v. Pretreatment of anesthetized dogs with UM-424, 10 mg/kg, provided complete protection against the development of premature beats and ventricular fibrillation when the left anterior descending coronary artery was occluded for 20 minutes and then released. UM-424 was effective in reversing ventricular arrhythmias in conscious animals which had been subjected to a two-stage ligation of the anterior descending coronary artery. The mean ectopic rate in a group of five dogs was 143 +/- 4.0 (S.E.M.) beats/min 24 hours after coronary ligation. Normal sinus rhythm was restored with a mean dose of 9.5 mg/kg of UM-424 and was maintained for a period in excess of 60 minutes. The ventricular fibrillation threshold was increased from a control value of 4.0 +/- 0.4 to 26.2 +/- 8.6 mA (P less than .05) 30 minutes after pretreatment with UM-424, 10 mg/kg. Inotropic and chronotropic dose-response studies to isoproterenol in the anesthetized dog demonstrated that the quarternary compound lacked beta adrenergic receptor blocking properties. UM-424, 10 mg/kg, did not produce any persistent changes in spontaneous heart rate, cardiac contractile force, left ventricular dP/ct, mean arterial blood pressure, cardiac output and mean pulmonary arterial pressure.


Acid secretion by guinea-pig isolated stomach. An isolated stomach preparation from the guinea-pig is described. 2. Both histamine acid phosphate (1-4 mug/ml.) and theophylline hydrate (0-2-3-2 mg/ml.) separately stimulated hydrochloric acid, HCl, secretion from the guinea-pig stomach preparation. A linear dose-response relationship was obtained for theophylline. 3. Addition of theophylline (0-2 and 1-6 mg/ml.) during maximal response to histamine increased the secretion further, whereas addition of histamine during maximal response to theophylline did not cause further secretion. 4. The secretory activities of Nalpha-MeH (0-3-5-0 muM), Nalpha-Me2H (1-2-9-5 muM) and 5-MeH (1-5-12 muM) were compared with histamine (0-9-13 muM) on a threshold background secretion induced by theophylline (0-2 mg/ml.). Linear log.-dose response relationships were obtained for each test drug. The results confirm that Nalpha-MeH is a more potent secretagogue than histamine. 5. Pentagastrin (0-3-1-0 mug/ml.) stimulated HCl secretion in approximately half the experiments. The response was often transitory. In the other experiments, pentagastrin had no effect on HCl secretion although subsequent administration of histamine did stimulate HCl secretion.


Two components of the calcium current in the egg cell membrane of the tunicate. The Ca current of the egg cell membrane of a certain tunicate, Halocynthia roretzi Drasche, was studied by the voltage-clamp technique. 2. The Ca current in the standard artificial sea water (ASW) was produced at the critical membrane potential of -10 mV after inactivating the Na current by conditioning depolarization, -30 to -15 mV. The Ca current was abolished by replacing Ca in ASW with Mg2+ or Mn2+. The Ca current was not significantly influenced by replacing Na in ASW with choline or Cs. 3. The relation of Ca current to the external Ca concentration was a monotonously increasing function, but was not linear. The current tended to saturate above 50 mM-Ca. In 100 mM-Ca ASW, the maximum peak inward current of Ca ranged from 1 to 7 X 10(-9) A. 4. The kinetics of Ca current was accurately analysed because of the small contribution of K outward current and was found to be relatively slow in comparison with the Na current. The peak time and the half-decay time of the maximum Ca current at about 25 mV were about 25 and 100 msec respectively in 100 mM-Ca ASW at 15 degrees C. 5. Addition of 20 mM-Co2+ to 100 mM-Ca ASW reduced Ca current to one fourth and 1 mM-La3+ to 100 mM-Ca ASW abolished the current. 6. Sr and Ba could substitute for Ca in Ca channels. The selectivity ratios for the 'Ca channels's were Ca (1-00):Sr(1-17):Ba(0-71) at a potential level of +40 mV. The Ca current in the egg cell membrane appeared to be essentially the same as the Ca current in the common excitable membranes, such as the crustacean muscle fibre. 7. The polyvalent cations including Ca ion and monovalent H+ ion showed the stabilizing effect upon both Na and Ca currents, by shifting V-I relations along the voltage axis. From the prediction of a theory of the diffuse double layer, the shift in the V-I relation induced by those cations should be directly related to their binding powers to the membrane. Thus, the sequence of the binding powers was inferred as H+ greater than La3+ greater than Co2+ greater than Mn2+ greater than Ca2+ greater than Sr2+ larger than or equal to Ba2+ greater than Mg2+. 9. In Na-free ASW, such as isotonic Ca ASW, Ca current was composed of two components. The one component was the Ca current described in 1 to 6. The other was also dependent upon the external Ca concentration, but showed the more negative critical membrane potential and the faster kinetics. It was concluded that this component should be the Ca current through Na channels. 10. The selectivity among Ca, Sr and Ba for 'Ca' current through 'Na channels' was significantly different from that of 'Ca' current through 'Ca channels', being Ca greater than Sr larger than or equal to Ba = 0.


Oestrogenic sensitivity of rat uterine secretion. Ovariectomized adult rats with closed uteri were treated for 7 days with different oral and s..c. doses of oestradiol, oestrone, oestriol and ethinyl oestradiol. All treatments elicited the production of uterine fluid and the potencies of oestrogens were related to the amount of fluid secreted. Ethinyl oestradiol and oestradiol displayed similar activity when given s.c. A daily dose of 0-003 mg oestradiol/kg resulted in about 700 mg fluid. Oestrone was 3-10 times and oestriol about 100 times less active. Orally, ethinyl oestradiol was the most potent substance and 700 mg secretion was obtained with a dose of 0-03 mg/kg daily. Oestradiol was about 30 times, oestrone about 100 times and oestriol 50 times less active than ethinyl oestradiol by this route. The viscosity of the secretion was unaffected, remaining between 1-6 and 2-4 cP. The pH of the fluid did not change, but that of the uterine lumen diminished slightly. These effects of oestrogens were associated with an increase in the weight of the empty uterus and a decrease in body weight.


A new series of cardioselective adrenergic beta-receptor blocking compounds. 1-(2-Acyl-4-acylaminophenoxy)-3-isopropylaminopropan-2-ols. A series of 1-(2-acyl-4-acylaminophenoxy)-3-isopropylaminopropan-2-ols has been synthesized and examined for beta-receptor blocking and antiarrhythmic activity. Several of these compounds are more than 20 times as active in blocking cardiac beta-receptors than vascular beta-receptors when given intravenously to anesthetized cats. The activities have been correlated quantitatively with partition and steric substitution constants. The observed relationships are consistent with a tentative proposal that the vascular receptor is situated in a more lipophilic environment than the cardiac receptor so that there is a differential transport effect between the two types of receptor.


Teaching interviewing for pediatrics.

Teaching interviewing for pediatrics. This paper describes a structured course for teaching interviewing which focuses on the interaction between the patient and the practitioner. Three main areas of learning were selected because of their universal application: relationship, communication, and feelings. Theoretical material is related to positive and negative interactions with patients, and these are described behaviorally in a checklist form. The development of good interviewing techniques consists of increasing the positive interactions and learning to use them as diagnostic and therapeutic tools. Different methods are utilized to help students apply these skills in clinical situations. Although this course was developed for a specific group of pediatric practitioners, it can be utilized by all types of health care professionals.


Effect of calcium on the membrane potential of Amphiuma red cells. An increase in extracellular Ca concentration causes the membrane of giant red cells of the salamander, Amphiuma means, to undergo a marked, transient hyperpolarization. This hyperpolarization is caused by an increase in K permeability of the membrane as judged from the K sensitivity of the membrane potential and from the rate of K loss under influence of raised extracellular Ca concentration. At constant external pH, the induction of hyperpolarization by increased extracellular Ca has a relatively well-defined threshold concentration. Furthermore the phenomenon is of an "all or none" type with most of the cells having membrane potential values either in the normal range (about -15 mV) or in the range -40 to -70mV. Shortly after suspension in Ringer's with 15 mm Ca, most if not all of the individual cells are hyperpolarized. Upon continued exposure (5-20 min) to the higher Ca concentration the membrane potential returns to the normal value in a fashion compatible with an "all or none" response. The observed Ca effect is sensitive to the pH of the suspending medium. At pH 6.2 the response is absent whereas the hyperpolarization is markedly stronger at pH 8.2 than at PH 7.2. It is argued that a reliable transport number for K under influence of Ca cannot be estimated from the slope of membrane potential vs. log (extracellular K concentration). This is probably related to the fact that the membrane potentials of the cells in the population do not stay constant in time. The above phenomenon is compared with the Ca-induced K permeability in poisoned human red cells or red cell ghosts. It is important to note that the cells employed in the present study are neither poisoned nor mechanically disrupted. This study emphasizes that the role of Ca in regulating cell membrane permeability to K seems to be a general feature.


Transitory postnatal hemolysis of calf red cells by amino acids. Among the amino acids which can be solubilized to give a concentration of 300 mm at near physiological pH, histidine and proline caused a complete hemolysis of newborn calf but not of adult cow red cells within 20 to 30 minutes at 38 degrees C. While hydroxyproline, valine, and serine resulted in a partial lysis of calf cells, threonine, glutamine, and glycine were ineffective. In this communication, emphasis has been focused on the mode of the lytic process by histidine which was found to be affected by several governing parameters including the pH, temperature and the extracellular salts in the solution. Unlike human red cells suspended in isotonic histidine, both calf and cow cells lost little Na and K ions. In the presence of 300 mm histidine, both calf and cow cells displayed an instantaneous uptake of histidine amounting to 20 to 45 mumoles/ml RBC followed by a slow influx rate of 0.25 to 0.5 mumoles/ml RBC X min. The extent to which histidine entry was allowed by the cell was counterbalanced by Cl- efflux, resulting in little change in cell volume prior to hemolysis. Moreover, histidine-induced hemolysis can be prevented by 1 mm or lower PCMBS without a discernible effect on histidine influx suggesting a possible membrane lesion or damage at the outer surface of the cell. Hemolysis induced by histidine decreased substantially when a calf reached two months of age at which time the red cells containing the fetal hemoglobin are virtually depleted. The results of hemoglobin electrophoresis obtained during this postnatal period revealed that those cells resistant to histidine hemolysis almost invariably contain the adult type hemoglobin suggesting a selective, specific action of the amino acids on the fetal cells.


ATP synthesis driven by a protonmotive force in Streptococcus lactis. An electrochemical potential difference for hydrogen ions ( a protonmotive force) was artifically imposed across the membrane of the anaerobic bacterium Streptococcus lactis. When cells were exposed to the ionophore, valinomycin, the electrical gradient was established by a potassium diffusion potential. A chemical gradient of protons was established by manipulating the transmembrane pH gradient. When the protonmotive force attained a value of 215 mV or greater, net ATP synthesis was catalyzed by the membrane-bound Ca++, Mg++ -stimulated ATPase. This was true whether the protonmotive force was dominated by the membrane potential (negative inside) or the pH gradient (alkaline inside). Under these conditions, ATP synthesis could be blocked by the ATPase inhibitor, dicyclohexylcarbodiimide, or by ionophores which rendered the membrane specifically permeable to protons. These observations provide strong evidence in support of the chemiosmotic hypothesis, which states that the membrane-bound ATPase couples the inward movement of protons to the synthesis of ATP.


Effect of local anesthetics on chloride transport in erythrocytes. The self-exchange of chloride isotopes across the human erythrocyte membrane was inhibited by tetracaine, benzocaine, and lidocaine. The inhibition by tetracaine was increased at higher pH values, but was not exclusively due to the uncharged form of tetracaine. The inhibition was effective within 5 seconds, was reversible, was non competitive with chloride ions, and was not reversed by calcium ions. These findings indicate that local anesthetics react with the erythrocyte chloride carrier at a site separate from the chloride site and cause inhibition of anion transport by a specific mechanism not involving changes in the surface charge density on the erythrocyte membrane.


Biochemical properties of cyclic nucleotide phosphodiesterase in metastasizing and nonmetastasizing rat mammary carcinomas. The biochemical properties of cyclic nucleotide phosphodiesterases in a nonmetastasizing and a spontaneously metastasizing rat mammary carcinoma were compared. The phosphooiesterases in both tumors had a pH optimum of around 8.0 and preferentially hydrolysed cyclic purine nucleotides. The rate of hydrolysis of purine nucleotides in the nonmetastasizing tumor was two times higher than in the metastasizing tumor, but the rate of pyrimidine nucleotide hydrolysis was equal in both tumors. Theophylline, caffeine, and D,L-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro20-1724) inhibited the enzyme activity in both tumors; the percent inhibition was the same by each inhibitor. The cyclic nucleotie phosphodiesterase activity in either tumor was stimulated by Mg++, Mn++, and Co++ and suppressed by Ca++, Zn,++, and Ni++. EDTA inhibited the activity below the basal level (activity in the absence of added cation), an this inhibition could be recovered up to the basal level by an equimolar quantity of either Mn++ or Mg++. Further stimulation of the enzyme activity with increasing concentrations of divalent cations was observed only with Mn++. Similar effects were observe with ethylene glycol bis(beta-aminoethyl ether)-tn,n-tetraacetic acid. The stimulatory cations affected both the low and high Michaelis constant (tkm) enzymes in these tumors by increasing the maximum velocity. In the low Km enzyme, the Km was also slightly increased. Neither guanosine 3',5'-cyclic monophosphate nor adenosine 3',5'-cyclic monophosphate had any effect on the hydrolysis of the other at physiologic levels.


Hybrid-versus-parental strain reaction. III. Comparative mortality in parental strain mice of the H-2k genotype. Lethally irradiated parental strain male and female mice were inoculated with marrow from reciprocal hybrid donors of the same sex. Hybrid cells homozygous for the H-2k genotype could recognize the quantitatively greater antigenicity of the parental strain CBA male recipients only. The more severe reaction occurred when the maternal strain of the hybrid donor was allogeneic to the recipient, which indicates the maternal effect on the antigen recognition system. This demonstration of a maternal influence on the expression of paternally derived tissue antigens made it possible to attribute the secondary disease syndrome to a hybrid-versus-parental strain reaction. The apparent differences in mortality between male and female recipients could not be attributable to X or Y chromosome disparity without additional transfers of appropriate marrow from males to females and females to males. In all cases, the parental strain-versus-hybrid reaction resulted in greater mortality than that observed in the hybrid-versus-parental strain reaction.


Cryptorchidism, hernia, and cancer of the testis. Risk of cancer of the testis was related to nondescent and hernia in a comparison of 596 testicular cancer patients and 602 unaffected men who had been in active service in the U.S. Army between 1950 and 1970. Medical histories were obtained from routine service records. Undescended testis was associated with a testicular cancer risk 8.8 times that of normal. Among cancer patients with a history of undescended testis, seminomas were nearly twice as frequent as in the remaining patients. Of 14 patients with unilateral undescended testis, 12 had the tumor on the side of the defect. Testicular cancer risk was estimated to be 2.9 times higher in men who had reported having had an inguinal hernia than in those who had not. Side of hernia and side of tumor were not associated; histologic type was not related to history of hernia.


Hemodynamic and respiratory responses of conscious swine to E. coli endotoxin. The injection of a sublethal bolus of E. coli into conscious swine produces an early increase in PAP and a decrease in LAP. This hemodynamic effect may be secondary to the pulmonary venous constriction seen in other species, or may relate to demonstrated multiple pulmonary microemboli. Hypoxemia developed in only four of 17 animals although all endotoxin-treated swine showed interstitial edema and elevated wet/dry weight ratios with normal pulmonary surfactant. In addition, endotoxin-treated swine developed signs of disseminated intravascular coagulation, with renal cortical infarcts in 44%, and coronary arterial thrombi in 28% including one transmural myocardial infarction. This effect was observed in the absence of prolonged hypotension in swine and should provide a useful model for further study of the relationship of endotoxin to disseminated intravascular coagulation.


Isoaccepting species of serine tRNA coded by bacteriophage T5sto. By aminoacyl-tRNA-DNA hybridization and chromatographic analysis, evidence was provided that the bacteriophage T5stO codes for two tRNAser species. Trinucleotide- or polynucleotide-stimulated binding experiments assigned the codons UCC or UCU to these two tRNAser species. They also suggested that the synthesis of these two tRNAser species does not modify the reading capacity for codons less used in Escherichia coli F and corresponds to a different situation compared with the T4-coded tRNA's.


Purification and characterization of mouse interferon with novel affinity sorbents. Several novel selective sorbents for mouse interferon are described that exploit the hydrophobic property and glycoprotein nature of this molecule. Low-molecular-weight ligands (hydrocarbons) and high-molecular-weight ligands (bovine serum albumin) immobilized on agarose bind selectively mouse L-cell interferon. The high selectivity of binding is due primarily to a hydrophobic effect, although electrostatic forces are also apparently involved. Mouse L-cell interferon binds to immobilized serum albumin and can be completely recovered by raising the ionic strength of the eluant. The specific activity of interferon preparations can be increased 2,000-fold to a value of 3 x 10(8) reference units per mg of protein in a single step with full recovery of the antiviral activity. A selective adsorption, although to a lesser degree, can be also obtained on hydrocarbon-coated agarose (Affi-Gel 202), resulting in 300-fold purification on desorption. The existence of two major components of mouse interferon was revealed upon its chromatography on the following sorbents: (i) bovine serum albumin-agarose, (ii) omega-carboxypentyl-agarose; and (iii) Bandeiraea simplicifolia lectin-agarose. This report thus provides for the first time a means for efficient and clear-cut separation of interferon components, thus enabling their further characterization.


Induction of prophage SPO2 in Bacillus subtilis: isolation of excised prophage DNA as a covently closed circle. Bacillus subtilis tryC2, thyA, thyB, lysogenic for the phage DNA polymerase negative mutant SPO2 susL244, was induced under conditions preventing phage and bacterial DNA synthesis. The biological activity of DNA from induced cells and from uninduced controls was assayed by transformation and transfection, respectively. About 50% of the phage DNA biological activity in DNA extracted from induced cells was resistant to exposure to pH 11.8 TO 11.9. This DNA was operationally defined as alkali-resistant phage DNA. Transforming bacterial DNA from uninduced or induced cells and transfecting DNA from uninduced cells were more than 95% inactivated after exposure to high pH. The alkali-resistant phage DNA was characterized by sucrose gradient centrifugation, by centrifugation in cesium chloride-propidium iodide, and by electron microscopy. It was found to consist of a majority of covalently closed circular DNA molecules. Length measurements of a few relaxed circular molecules indicate a molecular weight of these similar to that previously found for mature SPO2DNA. Attempts to isolate similar covalently closed circular phage DNA from induced bacteria lysogenic for SPO2 phage with a functional DNA polymerase gene were unsuccessful. The gene order in mature and prophage SPO2 was determined by rescue of single and double markers from the respective type of DNA. The data obtained show that prophage DNA is (genetically) permuted relative to mature DNA. The phage attachment site is suggested to be located between genes I and J.


Escherichia coli capsule bacteriophages. VIII. Fragments of bacteriophage 28-1. As described previously, a host capsule depolymerase activity is associated with the particles of Escherichia coli capsule bacteriophage 28-1. This is a large virus with a long, contractile tail terminating in a base plate with spikes. In the present work, isolated virions were exposed to a variety of dissociative reagents and conditions. They were then tested for residual infectivity and depolymerase activity, as well as inspected under an electron microscope. Very mild acid treatment (10 to 15 min at pH 4.0 and 37 C) was found to cause a specific detachment of some phage spikes, together with a moderate drop in both infectivity and depolymerase activity. Large batches of viruses were fragmented in this manner, and the detached spikes were isolated. The host capsule depolymerase activity was found to be associated with these organelles. In negatively stained preparations, the spikes exhibited a length of approximately 18 nm and a thickness of about 5 nm. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, they were found to contain polypeptides with molecular weights of 80,000 and 145, 000.


Studies on mode of antagonism between adrenergic beta-mimetics and beta-blocking agents (I). Beta-blocking action of mescaline and its derivatives. In order to clarify whether or not trimetoquinol (TMQ) and isoproterenol (ISO) interact with the same receptor, the pA2 values of propranolol (PR) and certain trimethoxybenzene derivatives were measured, using isolated guinea pig tracheal chains. Each of PR, mescaline (MES) and its derivatives gave almost the same pA2 values for TMQ and ISO. Introduction of an alkyl group into the N atom of MES increased the affinity to the receptor in the order of methyl and isopropyl as well as the structureactivity relationship of catecholamines, while that of hydroxyl group in the beta-position of the side chain decreased pA2 values. The slopes of the regression lines for anti-TMQ action of MES derivatives as well as PR were almost one, but those for their anti-ISO action were less than 0.3. 3,4,5-Trimethoxyaniline and 3,4,5-trimethoxybenzoic acid had little activity as beta-blocking agents. These results suggest the possibility that TMQ and ISO would interact with the same receptor sites. The importance of the trimethoxybenzene and the phenethylamine moieties in the MES-derivatives for anti-TMQ action is discussed.


Regulation of tyrosine hydroxylase activity by prostaglandin E1 in guinea pig adrenal gland. The action of prostaglandin E1 on tyrosine hydroxylase activity in adrenal slices of guinea pig was studied. The activity of tyrosine hydroxylase and was decreased by the incubation of adrenal slices with prostaglandin E1 at concentrations beyond 2 mug per ml for 2 hours. The activity of tyrosine hydroxylase was stimulated by dibutyryl adenosine 3',5'-monophosphate in slices of guinea pig adrenal glands. Incubation of adrenal slices wtth the combination of PGE1 and DBc-AMP lead to a tyrosine hydroxylase activity higher than that with PGE1 alone, but not as great as DBc-AMP alone. It was suggested that PGE1 inhibited the enzyme activity independently of the cyclic AMP level. Other prostaglandins such as PGA1 and PGB1 were deficient to the extent that the tyrosine hydroxylase activity was decreased. PGE1 inhibited the enzyme activity much to the same extent seen with protein synthesis inhibitors such as cycloheximide and actinomycin D. However, PGE1 did not influence the incorporation of L-leucine-14C into acid insoluble protein. The studies reported here showed that PGE1 inhibited the synthesis of tyrosine hydroxylase.


[The role of HCO3- ATPase in H+ /HCO3-Secretion (author's transl)]. Active buffer transport, e.g. H+ -secretion by stomach and kidney and HCO3--secretion by pancreas and salivary glands, is linked with the presence of a HCO3-stimulated ATP-Phosphohydrolase. In contrast to (Na+ -k+)-ATPase which is considered to be equivalent to the Na+ pump, the HCO3--ATPase requires only one ion for activation and is insensitive to ouabain. The HCO3--ATPase is found in the plasma membrane of the epithelia, but in contrast to the (Na+ -k+)-ATPase it is located in the luminal cell border. The activity of the HCO3--ATPase changes in parallel along with the rate of active buffer transport, a finding which underlines its importance as a transport enzyme. Several disorders of buffer transport are described which are possibly associated with a defect of the HCO3--ATPase system.


[Interlocking medullary nailing. Indications, technic with a new guiding instrument. Analysis of the 1st 50 operations]. After a review of Küntsher's intramedullary nailing, the author resumed the informations about the interlocking medullary nail and its technique. A new device, as a guide instrument for easier application of the transverse bolts was constructed on the basis of authors concept. Using the new technique and guide instrument X-ray television controll is not necessary for placing the bolts in their right places through a small incision. The time of operation and the risk of infection was also diminished by the new technique. The indications for the interlocking medullary nailing have been completed by the author with the pathologic fractures. The first 50 cases, treated by the new technique of the interlocking medullary nailing are analysed and a few cases are reported in detail. Good results have been obtained as regards both the bone union and the functional results. Based on the good results the new technique of the interlocking medullary nailing is recommended by the author.


[Tissue specific inhibition of lymphocyte proliferation by spleen extract (lymphocyte chalone) (author's transl)]. Aqueous spleen extracts were purified using acetone precipitation, membrane filtration, affinity chromatography, and dialysis. These extracts were able to inhibit thymidine incorporation into lymphoid cells (MKT-CH and PHA-stimulated lymphocyte cultures). They did not influence non lymphoid tissue (melanoma cells Mel Ei 78 and Ehrlich ascites cells). The inhibition was reversible and the purified extracts were not cytotoxic. The extracts correspond to a chalone. Their importance for prevention of graft versus host reaction and for treatment of lymphoproliferative diseases is discussed.


[Supporting role of the fibula in tibial fractures]. The possibilities of the supporting effect of the fibula and of its preclusion are discussed. The indication of the fibulotomia is dealt with. According to the authors' standpoint in the case of the anatomical reposition of the tibial fracture and after its staple synthesis the supporting effect of the fibula is not be be feared. In these cases the reposition and the osteosynthesis of the fibula neutralize fairly well also the motive forces acting on the tibial fracture.


[Clinical aspects and pathology of traumatic lesions of the optic nerve]. The cause of the unilateral complete blindness (amaurosis traumatica) occurring in the case of closed cranial injury has been sought for in the optic nerve canal (canalis opticus syndrome). For the decompression of the optic nerve surgical approach has been performed in several institutes and by various neurosurgeons. These interventions lead to no result, irrespective of the time of the operation or the surgical technique. On the basis of the data of the literature and their material the authors came to the conclusion that since the alteration of the optic nerve has been histologically observed not only in the area of the optic nerve, but also in the free intracranial and intraorbital sector, this was the cause of the failure. The authors' five cases are demonstrated with light and electron microscopic examinations.


[Preservation of crushed extremities].

[Preservation of crushed extremities]. For the conservation of crushed extremities all achievements of up-to-date traumatology are to be used. The impairement of the seriously crushed extremity displays a certain similarity to the polytraumatism involving the whole organism. This is to be taken into consideration in the surgical treatment. Conserving the vitality of the extremity deferred treatment and reconstructive operations at a later date become possible. As absolute rule must be in view that all cases are to be examined with the greatest care and individually, as regards the surgical treatment.


[Experience with the management of subtalar dislocation]. In 10 and 3 years resp., material of two surgical departments - with great material - 10 cases of luxation - without fracture - occurred in the subtaler joint have been treated. All 10 patients suffered covered, subtaler dislocations. After conservative treatment all 10 patients recovered and are back at work.


[Treatment of contracture of the finger joints by capsulectomy and spring-splints]. The treatment performed in 84 cases of contracted PIP articulations is reported, -in 50 cases the treatment has been carried out with spring-actuated splint and in 34 cases with capsulectomy. It has been found by the authors that the results of the physico-therapeutic treatment used so-far may be still more improved, -satisfactory result has been obtained in more than the half of the author's cases. The advantages of the use of the spring-acutatd splint as against Quengel's method are emphasized. Capsulectomy performed in very serious cases resulted in improvement of the articulation motion in 50% of the cases.


[Experimental single-stage reconstruction of the tendon sheath and flexor tendon (free tendon graft, using a vein for sheath on the flexor tendon in dogs)]. In dog experiments the flexor tendons of the 2nd toe together with their tendon sheaths have been extirpated by the authors. Then on the place of the tendon sheath complex-resembling the human hand's "no man's land" -for the substitution of the tendon sheath-free inautotransplants with long vein-segments have been grafted in one sitting. Resuming the results of the macroscopic and light microscopic examinations carried out in definite times it has been found by the authors that while the vein segment was revascularized in the course of one or two weeks, the regeneration of the tendon transplant was slightly retarded. Between the vein and the tendon but adhesion of medium degree were found. The possibilities of the clinical use of the method are discussed.


[Reconstruction of the injured flexor tendon in the proximal half of the "no man's land" by a modified method (tendon sheath reconstruction using a vein graft)]. On the basis of long years' experiences the "no man's land" has been divided by the author into 2 parts: the proximal and the distal part. For the treatment of the flexor tendon lesions occurred in the distal part of the author advocates his method already published: in the "tendon sheath" formed from the vein its "bridging" by free tendon transplant. If the lesion occurred in the proximal part, the formation of a long "tendon sheath" from a vein and then its "bridging" by long tendon transplant are advocated by the author.


[Isolated luxation of the trapezium bone]. The luxation of the os trapezium without fracture - a very rare lesion - is reported. This is the first publication in the Hungarian literature of this sort. Proper diagnosis was established after the patient's admission. Covered reduction of the luxation was made, and the luxated bone was fixed by percutaneous wiring and plaster-bandage. The patient recovered without complications.


[Amputation and rehabilitation].

[Amputation and rehabilitation]. Amputation is maybe the oldest and most frequent surgical intervention. After the review of the concept of rehabilitation, its methods and the improvement of the rehabilitation technique the earling opinions in respect of the height of the amputation, the surgical technique and the post-operative treatment - the use of a prosthesis included - are discussed by the author.


[Special care of injured patients after returning to work]. The changes in the type of injury, as well as in the treatment, and the consequences observed during the check-up of the injured patients set the problem of the prolonged care of the patients after the articular fractions of the lower extremity, amputation, arthroplasty, and severe lesions of the hand. Systematic observation, eventual change of the life and work conditions, temporary rest, conservative treatment or surgical intervention performed in due time allow the prevention of serious complications and assure lasting recovery.


Chemical injuries of the upper extremity. The prompt recognition and management (Tables 8-1 and 8-2) of chemical burns of the upper extremity may prevent injury to the deep structures of the hand and may make the difference between satisfactory rehabilitation and crippling deformities. Immediate irrigation with water is the single most important treatment that can be carried out, and should be continued for at least an hour and often for several hours, depending on the severity of the injury. Precious time should not be wasted hunting for a specific neutralizing agent. Hydrofluoric acid injuries and phosphorus injuries are the two exceptions to this principle. After copious irrigation and débridement, small superficial burns may be treated without dressings or topical therapy. Large partial-thickness burns are best treated with Sulfamylon burn cream and then with with biologic dressings until healing is achieved. Full-thickness injuries of limited extent should be excised and skin-grafted to regain maximum function, and more extensive burns treated in a nonexicisional regimen.


Intraspecific variations in the hemolymph of Biomphalaria glabrata, a snail host of Schistosoma mansoni. An attempt was made to characterize the hemolymph of Biomphalaria glabrata with reference to "normal" intra-specific variation, i.e., both inter- and intra-strain differences. Total protein concentration, per cent hemoglobin, pH, and osmolarity were studied. Seven geographic strains of B, glabrata were examined. In addition, observations were made on the hemolymph of Biomphalaria straminea, several strains of Helisoma caribaeum, and on B. glabrata subjected to infection with Schistosoma mansoni or to periods of starvation. Intra-strain differences in total protein concentration and total hemoglobin concentration in B. glabrata appeared to be more closely related with snail size than with absolute age. Inter-strain variation in B. glabrata was also noted, but the differences were of the same magnitude as those from intra-strain samples. Significant differences in total protein concentration were observed, however, between the means of similar size B. glabrata, B. straminea and H. caribaeum. The osmolatity of the hemolymph from different size B. glabrata was similar as were the osmolalities of the hemolymph from similar size snails of different strains. However, all B. glabrata strains exhibited hemolymph osmolalities lower than observed in strains of H. caribaeum. Infection with S. mansoni reduced the protein concentration of B. glabrata hemolymph. Differences were noted as early as 1.5-24 hr post-infection, with significant alterations occurring at about 11 days post-infection. To a lesser extent, starvation also depleted the protein content of the hemolymph.


[Relevance of biochemistry in diagnosis and development of alcoholic liver disease (author's transl)]. In a group of 205 patients with alcoholic diseases of liver the diagnostic relevance of biochemical tests (GOT, GPT, AP, GGTP, BSP) was reconsidered with discriminatory process (separation of diagnosis). The group contained 16 patients with nutritional-caused and 41 cases with alcoholic-caused fatty-infiltration of liver. 148 patients showed a toxic chronic liver disease; 52 a chronic hepatitis and 96 cirrhosis of liver. Laparoscopy and morphology guaranteed the clinical diagnosis and therefore the accuracy of biochemistry in separation of diagnosis was given. The biochemical tests were not able to offer a separation of fatty-infiltration with reference to cause, changes of the process in toxic hepatitis and cirrhosis were announced. Intersection in several cases was noticed and biochemical tests were not able to substitute endoscopy and morphology for clinical and diagnostic use in all cases. In every regard the enzyme-tests,--above mentioned--, and determination of sulfobromthalein are aptly to development of diseases and deficiency of alcohol.


Proline endopeptidase and exopeptidase activity in polymorphonuclear granulocytes. Peptidases capable of releasing proline residues from polypeptides are present in the cytoplasmic fraction of rabbit polymorphonuclear granulocytes. This was shown with peptide substrates where proline is present either at the carboxy-terminal or within the polypeptide chain. Lysosomal and plasma membrane enzymes were inactive towards such polypeptides. The proline residue was hydrolyzed at either its amino end or its carboxy end. It is noteworthy that a Pro:Pro bond was cleaved both in the pentapeptide Thr-Lys-Pro-Arg and the dipeptide Pro:Pro.


[A compact form of DNA in solution. 2. Peculiarities of acidic titration of double-stranded DNA in PEG-containing water-salt solutions]. The formation of compact double-stranded DNA molecules in PEG-containing watersalt solutions (0.3 M NaCl) may be observed within the pH-range 3-10; i.e. under conditions at which parameters of double-stranded DNA helices are not strongly different from those of B-form. At pH less than 3, when regularity of double helices is significantly changed, the formation of the specific compact particles of DNA in PEG-containing solutions does not take place. Denaturation of the compact form of DNA in PEG-containing solution is accompanied by disappearance of the negative band in CD spectrum. Hyperchromic effect of denaturation of DNA compact form is uninformative because of the influence of the light-scattering by compact DNA molecules.


[Changes in the chemical composition and physico-chemical characteristics of chromatin from spleens of mice during immunogenesis]. Comparative studies have been carried out for the chemical composition and physico-chemical characteristics of chromatin isolated from spleens of non-immunized and immunized mice. It is found that the chromatin from spleens of immunized mice contains significantly more non-histone proteins and RNA, while the quantity of histone proteins is unaltered. The melting temperatures of chromatin from spleens of non-immunized and immunized mice in 2.5-10(-4) M EDTA (pH 8.0) are 76.8+/-1.50 degrees and 74.4+/-1.10 degrees, respectively. DNA isolated from chromatin melts at 40 degrees. The melting of chromatin was followed in 5 mM sodium-cacodylate buffer (pH 7.0)+1.5-10(-4) M EDTA containing increasing concentrations of urea. The results show that during immunogenesis the changes of the chemical composition of the chromatin are accompanied by certain destabilisation of DNP complex.


Correction of severe combined immunodeficiency by fetal liver cells. As an alternative to bone-marrow transplantation, two infants with severe combined immunodeficiency who had no histocompatible donors were given intraperitoneal infusions of fresh liver cells from fetuses of eight and nine to 10 weeks. Transient graft-versus-host disease began at 42 and 52 days, respectively. Both infants had rises in T cells and declines in B cells by three months. No functional immunologic improvement occurred in the first infant, who died of pulmonary disease 10 months later. Clinical and functional immunologic improvement occurred in the other, who is now 19 months after transplantation. Lymphocyte responses to phytohemagglutinin and pokeweed mitogen were noted by three months, to concanavalin A by five months, and to allogeneic cells by eight months. Delayed cutaneous responsiveness to candida developed and IgM became norma. IgA and IgG remained low. Chimerism was demonstrated by a donor marker chromosome in metaphases from recipient lymphocytes. Fetal liver cells therefore reversed the immunodeficiency.


[Kinetics and mechanism of the 3H to 1H in C(8)H groups of purine derivatives]. The pH-dependence of the 3H to 1H exchange between water and C(8)H groups of purine, adenine, 9-methyladenine, 7-methyladenine, hypoxanthine, guanine, xanthine as well as C(2)H groups of imidazole and benzimidazole was studied. It was shown  that within the pH-ranges, where the majority of molecules under study are non-ionized, the values of observed rate constant (kobs) do not depend on pH. Beyond these ranges the values of k(obs) are increased or decreased depending on the type of ionizaiton of the compound under study in appropriate pH range. The observed pH dependence of the 3H to 1H exchange is in a good quantitative agreement with ylide mechanism of the exchange reaction. According to this mechanism the 3H--1H exchange takes place in N(7)-protonated forms of the purine derivatives and in zwitterions with positive charge on N(7). The ylide mechanism of the exchange reaction is also suggested by the fact that the true exchange rate constants (k+) of protonated forms of the studied compounds, calculated from the values of k(ods), rises linearly with the increase of their protonation constant (Ka1)--the tenfold increase of Ka1 leads to about four-fold rise of k+. The knowledge of 1h to 3H exchange mechanism in C(8)H groups of purine derivatives allows to estimate alterations of reactivity of the purine residues in polynucleotides and nucleic acids depending on their conformation.


Cyclic AMP and neuroendocrine influence upon forelimb regeneration in the adult newt, Notophthalmus viridescens. The influence of the nervous and endocrine systems upon successive stages of limb regeneration suggest possible neuroendocrine interaction(s). Intraperitoneal injections of various agents had no effects upon blastema formation. Chlorpromazine, administered alone or with hormones, retarded morphogenesis. Prolactin, dibutyryl cAMP (db-cAMP), theophylline, and acetylcholine accelerated morphogenesis. 5'-AMP had no effect. Only db-cAMP countered the chlorpromazine-induced retardation of morphogenesis. These results suggest that neuroendocrine influences, possibly cAMP-mediated, direct, in part, the morphogenesis of the regeneration blastema.


Impaired urinary acidification in the hypothyroid rat. Since abnormalities in the renal handling of sodium and water in both the proximal and distal tubule have been described in primary hypothyroidism, this study was undertaken to examine renal tubular hydrogen secretion in this disorder. Metabolic acidosis was induced in hypothyroid rats (H) and their age matched controls (C) by the administration of an oral ammonium chloride load of 0.15 g/24 h/kg for three days. On day 3 animals were prepared for clearance and acid-base studies, receiving an infusion of Ringer's solution of 0.6 ml/hr/100 g during surgery and the experimental procedure. A 26% decrease in GFR (P less than 0.005) and a doubling in fractional excretion of sodium (P less than 0.02) were observed in H rats. The lowest blood pH and average bicarbonate concentration and the excretion of chloride were similar in the two groups, indicating that the acid load was reabsorbed and led to similar degrees of systemic acidification. Urine flow also was comparable in the two groups. Minimal urine pH after NH4Cl was 6.21 +/- 0.06 in H and 5.68 +/- 0.09 in C (P less than 0.001). Ammonium excretion was 28% (P less than 0.05) lower in H than in C. The defect in urine acidification in H was only partially corrected after 5 days on a low sodium diet and DOCA administration for 2 days. Fractional bicarbonate excretion at normal blood pH and bicarbonate concentration was not different in the two groups. These data indicate that hypothyroid rats have a mild defect in urine acidification and that it is localized predominantly in the distal tubule.


[2 new species of microsporidians (Protozoa, Microsporidia) from mosquitoes of the family Chironomidae]. Two new species of microsporidians are described from the mosquitoes of the genus Chironomus collected in water bodies of the north-eastern USSR. Bacillidium chironomi sp. n. injuring the adipose tissue of the fourth stage larvae of Chironomus dorsalis Mg. has rod-shaped spores 15 (11 to 19) x 0.7 (0.6 to 0.9) mu in size. Duboscqia chironomi sp. n. injures the adipose tissue of the fourth stage larvae of Chironomus plumosus L. Fresh spores of this species are egg-shaped, 6.2 (5.8 to 6.5) x 3.8 (3.6 to 4.0) mu in size. When stained according to the Romanovsky-Gimza method the spores are 5.4 (4.9 to 5.8) x 3.8 (3.6 to 4.1) mu in size. Some peculiarities of the nuclei fission in the sporants of Duboscqia chironomi sp. n., are discussed.


Electrical responses of isolated Nitella protoplasm--excitations or artifacts? Isolated protoplasmic droplets of the alga Nitella were investigated with microelectrodes under current clamp conditions. The following observations were made: 1. Long pulses of either polarity yielded almost symmetric current-voltage relations. Near the rather small resting potential (inside negative) the measuring points lay on a straight line corresponding to an apparent surface membrane resistance of 1.7 +/- 0.45 komega (mean +/- S.E.M., n=5). 2. Experiments with various pulse programs revealed no mechanism comparable to Na inactivation but stressed the electrical symmetry of the droplet with respect to the resting potential. 3. Changes of the [Ca2+] in the bathing medium between 0 to 10 mM as well as of the pH between 5 and 9 did not influence the responses. Replacing K+ by Na+ (or vice versa) or exchanging NO3 for acetylglycine or Cl- was also ineffective. These observations are not consistent with a normal excitable surface membrane. Similar responses are obtained with a RC network which is described and which may have its substrate in histological peculiarities of the protoplasmic droplet.


The action of Ca2+ , Mg2+ and H+ on the contraction threshold of frog skeletal muscle: Evidence for surface charges controlling electro-mechanical coupling. The dependence of the threshold potential for contraction of pH and the concentration of Ca2+ and Mg2+ in the bathing solution was measured in frog skeletal muscle. Decreasing the pH from 10.3 to 4.65 resulted in a threshold shift to more positive potentials. Between pH 6.5 and 8.5 the concentration threshold was almost pH -independent. Increasing [Ca2+]o (in the concentration range 0.5-50 mM) shifted the curves relating contraction threshold to pH to less negative potentials and diminished the overall pH-dependence. The contraction threshold exhibited a similar dependence on [Ca2+]o and [Mg2+]o, the two curves running parallel in the concentration range of 5-50 mM, but Mg2+ was only c. 0.6 as effective as Ca2+. To explain these results a surface charge model is proposed which assumes that two acidic groups, sigma1 and sigma2, and one basic group, sigma3, reside at the outer surface of the membrane of the T-system. Alterations in the extracellular medium exert their influence on the electro-mechanical coupling process by changing the surface potential. The groups will be titrated by protons and their charges screened off by the divalent cations. In addition, Ca2+ was supposed to bind with a weak dissociation constant (23 M) to the two acidic groups. The chosen charge densities are: sigma1 = -0.0085/A2 [= -1e/(10.8 A)2], sigma2 = -0.0037/A2 [= -1e/(16.4 A)2], sigma3 = 0.0028/A2 [= + 1e/(18.9 A)2] with intrinsic dissociation constants KH1 = 10(-2.0)M, KH2 = 10(-4.1)M, and KH3 = 10(-8.5) M. The measured threshold values are satisfactorily described by this model except at extreme alkaline and acid pH values.


[Comparison of the pA2 of various beta blocking agents]. The drug industry is now putting out specific beta 1 or beta 2 beta-blocking agents. The pA2 of various beta-blocking agents were determined on isolated organs-guinea pig atrium and trachea: practolol and acebutolol were considered as specific beta-1 inhibitors; butoxamine was a specific beta-2 inhibitor, while pindolol, oxprenolol, propranolol and alprenolol were specificity free. The pA2 quantifies the action exerted by an inhibitor. Cardioselectivity is expressed by the pA2 left atrium/pA2 trachea ratio. It exceeds 1 000 for practolol, it equals 30 for acebutolol, and is very slight for butoxamine. The pA2 therefore gives a good idea of the potential of the various drugs on the animal's isolated organ. However, these data cannot safely be extrapolated to man. Hence the necessity of conducting clinical pharmacological studies.


[Effects of adrenergic blockade on adipose tissue lipolysis provoked in cats and humans by intravenous perfusion of isoprenaline]. An intravenous infusion of isoprenaline (1 mug/kg/mn during 4 h) elicited a rise in serum free fatty acids (FFA) and glucose in anaesthetised cats. The effect reached a peak in 1 h and was then maintained at a plateau level for the remainder of the infusion. Acebutolol and practolol (0,1-10 mg/kg, p.o.) were more potent in reducing the concentration of free fatty acids (FFA) than in lowering glucose. Propranolol was roughly equipotent on FFA and glucose. In 6 fasted human volunteers, an intravenous infusion of isoprenaline (0,03 mug/kg/mn during 15 min) stimulated a rise in serum FFA. Peak values were attained rapidly and FFA levels began to fall soon after the end of the infusion. Blood glucose concentration was not changed. A placebo, given after the first infusion of isoprenaline, did not significantly affect the response to 2 further infusions at 2 and 4 h later. An oral dose of acebutolol (300 mg) largely suppressed the lipolytic effect of the 2nd and 3rd isoprenaline infusions, the degrees of inhibition being 70 p.cent and 85 p.cent respectively. The same dose of practolol was considerably less effective in inhibiting lipolysis (37 p.cent and 25 p.cent inhibition).


Bone marrow transplantation in children. Bone marrow transplantation is a new concept in the treatment of leukemia and aplastic anemia. The problems seen in the transplanted patient are abundant and often life-threatening. Caring for these patients offers one of the most exciting challenges of nursing. The nurse not only acquires skill in caring for a patient with leukemia and aplastic anemia, but also becomes knowledgeable in infectious diseases, immunology, fluid and electrolyte balance, and cardiac, respiratory, and renal diseases. The complexity of these patients allows the nurse more direct, comsistent contact with them. As she becomes involved, she is given excellent opportunities for supporting the patient and family through this stressful time. Althoug bone marrow transplantation is an experimental procedure with problems still to be solved, results indicate its value in the treatment of refractory leukemia and aplastic anemia.


Control of adenylate cyclase from secretory vesicle membranes by beta-adrenergic agents and nerve growth factor. Adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity of purified secretory vesicle membranes from the adrenal medulla is inhibited by I-isoproterenol and I-epinephrine, as well as by nerve growth factor (NGF). The effect of these agents was found to be dose-dependent and, in the case of the catecholamines, saturable. NGF was active at concentrations as low as 10(-8) M. Oxidized NGF was only minimally active, and insulin was completely inactive. Neither dopamine nor phenylephrine had activity. Inhibition of cyclase by either isoproterenol or epinephrine was blocked by I-propranolol, a specific beta-antagonist, but propranolol by itself had no effect on adenylate cyclase activity. The data indicate that the secretory vesicle membrane has beta-adrenergic receptors coupled to the adenylate cyclase. Propranolol was also found to block the NGF-induced inhibition of cyclase. We conclude that the granule membrane has beta-adrenergic receptors as well as NGF-reactive sites, and that the two may be functionally linked.


Preliminary characterization of the acrasin of the cellular slime mold Polysphondylium violaceum. Some species of cellular slime mold do not respond to cyclic AMP as an acrasin, or chemoattractant. In one such species, Polysphondylium violaceum, we have isolated and purified its acrasin and determined some of its chemical properties, which lead us to believe it is a small molecule of less than 1500 daltons. One possibility is that it might be a peptide. The acrasin specifically attracts the amoebae of P. violaceum and P. pallidum and fails to do so for six species of Dictyostelium tested. We also have evidence for a specific acrasinase that inactivates the Polysphondylium acrasin.


[The effect of hydrocortisone and insulin on the activity and isoenzymes of typrosine-alpha-ketoglutarate transaminase in the ctyostructures of the livers of rats of different ages]. Administration of hydrocortisone or insulin and also a simultaneous use of these hormones in a high dose caused a marked elevation of the total activity of tyrosine-alpha-ketoglutaric transaminase and its anode and cathode isoenzymes in the soluble fraction of the liver in the sexually immature (weighing 100-110 g) and mature (weighing 180-200 g) male rats. The stimulating effect of insulin was sharper in the young in comparison with adult animals. Administration of hydrocortisone caused a more pronounced elevation of the total tyrosine-alpha-ketoglutaric transaminase activity in the hepatic mitochondria of young rats than in adult animals. Insulin administration increased the activity of tyrosine-alpha-ketoglutaric transaminase in the mitochondria of the liver of the sexually mature male rats without significant changes of this enzyme in the sexually imature rats. A simultaneous injection of hydrocortisone and insulin to the sexaully mature male rats caused the same increase in the tyrosine-alpha-ketoglutaric transaminase activity in the hepatic mitochondria as after the administration of glucocorticosteriod alone. As to the sexaully immature males, the activity of the enzyme fell to the normal level. It is supposed that androgens played a significant role in the realization of the inducing action of glucocorticoids and insulin influencing the synthesis of tyrosine-alpha-ketoglutaric transaminase in different directions in the mitochondria of the liver of young and sexually mature animals.


Effects of dietary vitamin D and calcium on lysyl oxidase activity in chick bone metaphyses. Activity of lysyl oxidase, an enzyme responsible for production of aldehydic precursors for lysine-derived collagen crosslinks, was measured in tibial metaphyses from chicks receiving different dietary levels of vitamin D and Ca for 2 weeks after hatching. Enzyme activities were increased twofold in D-deficient chicks compared to activities from chicks receiving control levels of vitamin D. Addition of Ca to the D-deficient diet had no effect on lysyl oxidase activity. It is suggested that vitamin D may play a role in the age-related decrease in lysyl oxidase activity that normally occurs in chick bone.


Factors influencing nonspecific binding of glucocorticoids in myocardial tissue. Myocardial slices from the left ventricle of cat hearts were incubated in Krebs-Henseleit buffer containing 10 mM glucose which were gassed with 95% O2 and 5% CO2. Tritiated dexamethasone (DEXA 0.171 MM) or methylprednisolone (MP 0.805 mM) was added under varying conditions of temperature, pH, and in the presence of various metabolic inhibitors. Glucocorticoid uptake by myocardial tissue was found to be temperature-dependent, plateauting after 60 min of incubation at 0.21 mumole of DEXA/g of tissue and 0.95 mumole of MP/g of tissue at 37 degrees. Steroid uptake was retarded about 50% at 0 degrees. Increasing the concentration of either steroid resulted in a linear increase in the uptake of that steroid. Incubation in the presence of metabolic or SH-inhibitors produced no significant changes in glucocorticoid uptake. Optimal glucocorticoid uptake occurred between pH 7.3-7.4. Thus, myocardial cells appear to be able to take up large quantities of glucocorticoids, but the uptake process does not appear to be energy-dependent.


Arylamidase and cathepsin-A activity of normal and dystrophic human muscle. Human skeletal muscle homogenate has been shown to contain enzymes that catalyze the hydrolysis of L-leucyl p-nitroanilide and carbobenzoxyglutamyl-L-tyrosine, known substrates, respectively, for arylamidase and cathepsin A. The muscle arylamidase was found to be inhibited by p-chloromercuribenzoate. Addition of Co2+ resulted in slight stimulation of its activity. Neither ethylenediamine tetraacetate nor thiol compounds had any appreciable effect on the enzyme. When compared to controls, no significant differences in muscle arylamidase levels were observed in patients with muscular dystrophies and certain selected neuromuscular diseases. Cathepsin A was, however, increased in muscles moderately affected by muscular dystrophy and denervating diseases.


Synthesis of some new phenothiazine derivatives of expected medicinal value. 2-Chloroacetyl phenothiazines were reacted with certain phenols and salts of some acids under different conditions to yield 2-substituted acetylphenothiazines. Another series of 10-substituted phenothiazines was synthesized by treatment of 10-chloroacetylphenothiazine with either the appropriate amines or salts of the respective acids. The optimum experimental conditions for the preparation of 2-chloroacetyl-10-acetyl-phenothiazine by Friedel-Crafts reaction were studied. Also N-chloroacetyl-o-aminophenol was synthesized in high yield by a simple method. The preliminary pharmacological screening showed that two of these compounds possess a low order of tranquillizing activity.


Morphological changes in the thymus of young and adult red-billed queleas Quelea quelea (aves). In a wild population of red-billed queleas Quelea quelea L. (Ploceidae: weaver-birds) sampled throughout the year in East Africa, the thymus was found to enlarge in young birds shortly after hatching, remain enlarged during the juvenile stage, and regress towards the end of the postjuvenile moult. In adults, recrudescence occurred in many individuals during the prenuptial and postnuptial moults, and also in most if not all individuals, of both sexes, for a brief period during a breeding session. Thymus enlargement in both young and adults has been found to be accompanied by marked erythropoietic activity within the gland, and it is suggested that this activity is related to an increased demand for erythrocytes which may occur during moult and breeding.


Histological changes associated with enlargement and regression of the thymus glands of the red-billed quelea Quelea quelea L. (Ploceidae: weaver-birds). Thymic lobes form over 200 red-billed queleas, Quelea quelea L., were examined histologically. Samples were taken from embryos about to hatch, juveniles and adults. The lobes varied in size from very small to very enlarged (1- greater than 5 mm long). The constituent cell types are described in detail and the occurrence of these cells in different sized lobes is discussed. A cycle of events is proposed which accounts for the observations presented here. It is suggested that the large numbers of erythroid cells found in the cortex of some individuals were developing in situ. The significance of erythropoiesis within the thymus is discussed.


EMMA-4 analysis of iron in cells of the thymic cortex of a weaver-bird (Quelea quelea). Combined morphological and analytical studies with the EMMA-4 analytical electron microscope have enabled very early erythroid cells to be identified within the cortex of enlarging thymic lobes of Quelea quelea. These early erythroid cells have pale cytoplasm (sometimes with ferritin-like crystals present), slightly pachychromatic nuclei and have fewer cell organelles (mitochondria) than lymphocytes. Counts for iron were approximately 70% lower than counts from mature erythrocytes found free in the cortex. Iron was also recorded from some epithelial reticular cells and pyknotic nuclei; no iron was recorded from small lymphocytes (thymocytes) in the cortex. The presence of very early erythroid cells is a further indication that erythropoiesis occurs in situ in the avian thymus.


The postcranial skeletons of the Triassic mammals Eozostrodon, Megazostrodon and Erythrotherium. The purposes of this monograph are to describe the postcranial skeletons of the earliest known mammals, and to probe, in so far as possible by osteological study, biological questions concerning the habits and adaptations of these late Triassic forms. In this context, information on the background of this investigation is useful. Studies of Mesozoic mammals, begun some 150 years ago, are based on rare and fragmentary fossils, principally jaws and teeth. These investigations have yielded a bare outline of some 120 million years of mammalian evolution-about two-thirds of mammalian history. No assessment of the important biological changes occurring during this time can ever be complete, but major advances are possible as new discoveries provide material that is more complete or that represents a previously unknown evolutionary stage. So tenuous is the evidence that at least some concepts are re-evaluated with each discovery. Postcranial anatomy offers especially intriguing prospects for investigation because associated material (that can be positively assigned to a taxon below subclass) has been for the most part unknown, and indeed even dissociated bones are a rarity. Since G.G. Simpson's monographs of 1928 and 1929, progress in the study of Mesozoic mammals has been largely dependent on new finds. A major impetus to renewed investigation came from the discoveries of Mesozoic mammals by Walter Kühne in 1939 and during the immediate post-war years. Kühne first worked on fissures in the Carboniferous limestone quarries at Frome, Somerset, in southwest England where he collected a series of teeth of the problematical form Haramiya and two triconodont teeth which were placed in the genus Eozostrodon (Parrington 1941, 1946). The fissure faunas are generally thought to be of Upper Triassic (Rhaetic) age (Kühne 1946), although Kermack, Musset & Rigney (1973) believe that the evidence is insufficient to determine whether the deposits are Rhaetic or Lower Liassic. After the war Kühne carried his explorations farther west, eventually reaching the quarries at Bridgend in Glamorgan, Wales, where he not only found more triconodont teeth in some quantity (Kühne 1958) but also a symmetrodont tooth (Kühne 1950). Shortly after making these discoveries, Kühne returned to Germany and the work was continued by a team from University College, London, under the leadership of Dr K.A. Kermack.


Classical conditioning in the sea anemone, Cribrina xanthogrammica. Earlier attempts to classically condition sea anemones have yielded inconclusive results. Using light as CS and shock as US, conditioning as distinguished from sensitization and pseudoconditioning was demonstrated in anemones. Procedural controls included substitution of light alone, shock alone, and random light and shock in place of paired light-shock trials. Responses measured were electrical output and folding of the oral disc. The conditioned response was distinguished from the unconditioned response to light and the unconditioned response to shock in terms of response latency of both electrical and behavioral measures.


Performance enhancement effects of d-amphetamine, methylphenidate, pipradrol and phenindamine in rats. A multiple behavioral schedule with food reinforcement was designed to measure the drug-induced performance enhancement and non-effective activity in rats. The schedule, 20 min in duration, had CRF components in the 33 trials and extinction components in the inter-trial periods. During each trial, food reinforcement was present in the limited period (8 sec each) which was preceded by a discriminative stimulus (1 sec, either a light or a footshock). The rats generated a high rate of lever pressing during the limited period and a low rate of lever pressing during the inter-trial period. The drugs studied were d-amphetamine, methylphenidate, pipradrol and phenindamine. At low dosages, these drugs increased further the high rate of lever pressing. This was considered to be the performance enhancement effect. At higher doses, the drugs increased the low rate of lever pressing, decreased the high rate of lever pressing, and decreased responding of the rats to the discriminative stimulus. This latter pattern was considered to be the non-effective activity caused by the drugs. As expected, d-amphetamine was the most potent. Minor differences in drug effects were seen between the group of rats having light and that group having footshock as discriminative stimulus.


[Automatic method for determination of serum antistreptolysin]. The AA. describe a method of determination of serum antistreptolysin employing "Technicon" AutoAnalyzer, this method permitting the execution of 40 determinations in an hour, with a time of analysis of about 16 minutes. The procedure of analysis is very easy, with a very high selectivity of values; a variation coefficient of 5,3% and an accuracy index of 4,4% were found. Since the amount of serum employed is 50 mul this method appears to be particularly suitable in paediatry and in serological screening.


On the influence of prostaglandin F2alpha-induced labor at term on the metabolism and coagulation of mother and fetus. 11 pregnancies at term were terminated by dilatation of the uterine cervix, low amniotomy, and by intravenous administration of PGF2alpha. The average infusion time was 3 hours 55 minutes, and the average total dose of PGF2alpha amounted to 2.0 mg. Parameters of acid-base changes, carbohydrate and energic state changes, gas metabolism, and changes in coagulation and fibrinolysis in mother and in fetus were analyzed during labor and after birth. Labor activity and fetal cardiac action were monitored cardiotocographically. Checked against 50 uncomplicated spontaneous deliveries, we found no disadvantageous changes in the parameters investigated.


Pulmonary microembolism: attenuated pulmonary vasoconstriction with prostaglandin inhibitors and antihistamines. The mechanism(s) involved in the pulmonary vascular and airway responses to pulmonary microembolism have not been clearly defined. Therefore, we determined the effects of specific prostaglandin and histamine blockade on the hemodynamic and arterial blood gas tension responses to particulate microembolism (200 mu glass beads) in intact anesthetized dogs. The marked increases in pulmonary arterial pressure and pulmonary vascular resistance observed in the untreated dogs were attenuated, but not abolished, following both prostaglandin blockade (with either meclofenamate or polyphloretin phosphate) and histamine blockade (with chlorpheniramine and metiamide) at 5 minutes, and were still attenuated 30 minutes post embolization. Combined prostaglandin and histamine blockade further attenuated, but again did not abolish, the pulmonary vascular responses. Cardiac outputs and systemic arterial pressures were unchanged from control by embolism. The alveolar hypoventilation (decreased arterial oxygen tension and increased carbon dioxide tension) observed in the untreated embolized dogs was prevented only with the prostaglandin inhibitors. Pulmonary microembolism in intact dogs, therefore, appears to induce vasoconstriction mediated partially by prostaglandin and histamine action, and alveolar hypoventilation mediated by prostaglandin, but not histamine, action.


Carotid body control of coronary flow, myocardial oxidative metabolism, and cardiac catecholamines in the dog. In a series of 11 dogs, selective stimulation of the carotid body receptors by hypoxic, hypercapnic, acidotic blood produces bradycardia, an increase of coronary flow, and greater release of norepinephrine from the heart; the coronary resistances are decreased. The same stimulation after vagotomy is no longer accompanied by bradycardia; the decrease of coronary resistance is less marked and the release of norephinephrine is increased.


Noradrenergic subsensitivity of rat liver homogenates during chronic ethanol ingestion. Prior studies indicated that chronic ethanol feeding induced noradrenergic subsensitivity of the cerebral cortex. Sensitivity was measured using the cAMP response of brain slices to norepinephrine (NE). In the present report we investigated the possibility that noradrenergic receptors in a visceral organ might be similarly affected by ethanol feeding. The cAMP response of liver homogenates to NE was measured. Chronic ethanol ingestion induced subsensitivity of the liver to NE similar to that observed in the brain. The ED50 was shifted to the right from 2.1 X 10(-5) M to 1.3 X 10(-4) M NE. By 3 days of ethanol withdrawal the cAMP response returned to control levels.


Interactions between drugs and saliva-stimulating parafilm and their implications in measurements of saliva drug levels. The interaction between Parafilm and four tranquilizers in their neutral phosphate buffer solutions resulted in various degrees of loss of the drugs from the solutions. The values of loss ranged from 15 to 34% for chlorpromazine and 8 to 42% for butaperazine at the initial concentration range of 2 to 20 mug/ml at room temperature (22 +/- 1 degree C). Under the same conditions, the values of loss from saliva for these two drugs were fairly constant; about 25% and 17%, respectively. For diazepam and chlordiazepoxide, the losses from the buffer solution were below 5%.


Acid hydrolases in the odontoblast-predentin region of dentinogenically active teeth. The presence of hyaluronoglucosidase (EC 3.2.1.35; hyaluronidase), beta-N-acetylglucosaminidase (EC 3.2.1.30), exo-1,4-beta-xylosidase (EC 3.2.1.37), and arylsulfatase (EC 3.1.6.1) in dentinogenically active odontoblasts isolated from the rat incisor has been demonstrated by means of biochemical methods. The possible function of these enzymes in relation to the calcification process is discussed.


N-acetyl-beta-D-hexosaminidase system in synovial fluid. The present study was undertaken with the object of examining the N-Acetyl-beta-D-hexosaminidase activity in joint effusions from non-inflammatory (osteoarthrosis) and inflammatory (rheumatoid arthritis, gouty arthritis and chondrocalcinosis) joint diseases. The biochemical properties of four purified molecular forms were investigated. They were separated on the basis of their net charge, using DEAE-cellulose anion-exchangers. In the order of their outcome from the anion exchanger the four enzymes (B, I1, I2 and A) were found to have pH optima at 4.5-4.75, 4.20, 4.00 and 4.75, respectively. The first three enzymes proved to be heat-stable and the fourth enzyme fraction was a heat-labile form. By means of gel-filtration techniques, the enzymes were eluted into two fractions. The first contained the thermolabile A form and the molecular weight of this enzyme was estimated at 162000. The second fraction included the three thermostable enzymes. Their molecular weight was estimated at 135000. As described by Ikonne & Ellis (6) the hexosaminidase A from sera was less tightly held by the anion-exchanger than was the hexosaminidase A from tissues (polymorphonuclear cells, synovial membrane tissue, cartilage). Thus the serum type (As) must be distinct from the tissue type (At). The activity of the tissue type probably originating from the leukocytes and from the synovial membrane was more pronounced in the synovial effusions of the patients with inflammatory joint diseases. The hexosaminidase A fraction from synovial fluids of patients with osteoarthrosis contained only the serum type of enzyme.


[Gastroenterology yesterday and today].

[Gastroenterology yesterday and today]. In the 40 years since the foundation of the "Schweizerische Gesellschaft fur Gastroenterologie", medicine - and with it gastroenterology - have markedly changed. New diseases and syndromes have been discovered and others have disappeared. New knowledge in basic sciences influences progress in diagnosis and therapy. In diagnostic methods the most evident advances are fiberendoscopy, endophotography and biopsy, and progress in roentgenology and immunology. New drugs, new surgical methods and controlled trials have improved treatment. However, each advance has its drawbacks: the growing incidence of iatrogenic diseases, the overwhelming literature, the flood of congresses, the record-breaking mentality of many clinicians and the hunting and collecting instinct for "interesting cases". "Medical art", a notion difficult to define, is in danger of disappearing. It means a harmony of knowledge, skill experience, intuition and the predominant desire to help the patient. This means individualized medicine, which is only possible by sympathetic dialogue with the patient - not only by specialists in psychiatry or psychosomatics, but by every doctor. will be able to preserve medicine from inhumanity in spite of technology, rationalization and the computer?


Sperm diaphorase: genetic polymorphism of a sperm-specific enzyme in man. Human sperm contains en enzyme with diaphorase activity that appears to be unique to sperm. Electrophoretic analysis of the diaphorase activity in sperm of different individuals reveals three phenotypic patterns. This polymorphism can be explained in terms of two alleles segregating at an autosomal locus; the allele frequencies have been determined to be 0.71 and 0.29. This appears to be the first reported example of a sperm-specific genetic polymorphism in man; its existence raises a number of genetic and biochemical questions.


Acid precipitation and embryonic mortality of spotted salamanders, Ambystoma maculatum. Spotted salamanders breed in temporary pools formed in early spring by melted snow and rain. Many of these pools reflect the low pH of precipitation in the northeastern United States. Egg mortality is low (less than 1 percent) in pools near neutrality, but high (greater than 60 percent) in pools more acid than pH 6. Developmental anomalies and the embryonic stage at which death occurs are the same in field situations as at corresponding pH's in laboratory experiments.


Antibodies to histones and histone-histone complexes: immunochemical evidence for secondary structure in histone 1. Highly specific antibodies were raised to histone 1 (H 1) and the histone complexes H32-H42 AND H2A-H2B, isolated by salt extraction. Antibody to H1 could detect irreversible conformational changes in acid- or urea-treated H1. The antibodies showed different reactivities with chromosomes as compared to antibodies in acid-extracted histones and should be useful in studies of native chromatin and chromosome structure.


Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Tritiated haloperidol and tritiated dopamine label postsynaptic dopamine receptors in mammalian brain. Clinical potencies of butyrophenones, phenothiazines, and related drugs correlate closely with their ability to inhibit tritiated haloperidol binding. These binding methods provide a simple in vitro means for evaluating new drugs as potential antischizophrenic agents.


Vector control of filariasis in the Solomon Islands. In Solomon Islands, filariasis is caused by the nocturnally perodic form of Wuchereria bancrofti and is transmitted by the same vectors of malaria. This study explores the control of this disease as an additional effect of the Malaria Eradication Programme.


Standardisation of the preparation of platelet concentrates. Platelet concentrates with a yield of 80,8% and an absolute number of platelets per pack of 0,86 X 10(11) were obtained, using an optimised harvesting method. This method involved standardised collection of whole blood with constant mixing of blood and anticoagulant, a first centrifugation at 750 g for 6 minutes at 22 degrees C (full brake) and a second centrifugation at 2 0000 g for 20 minutes at 22 degrees C (half brake). Resuspension of the platelet pellet in plasma was effected by leaving the pack at room temperature for 30 minutes. Platelet concentrates of 25 ml and 50 ml volume displayed satisfactory pH and count characteristics after 72-hour storage both at room temperature and at 2 - 10 degrees C.


Suppression of postpartum lactation with furosemide. A regimen of fursemide and moderate restriction of fluid intake was followed in 120 postpartum women to suppress lactation. The methods and results are presented, and possible mechanisms whereby furosemide may suppress lactation are discussed.


[Changes of protein metabolism following irradiation. II. Protease activity, protease pattern, protein and free amino acids in the cytoplasm and cell organelles of the rat liver following 600 R whole-body irradiation]. The protease activity of cytoplasm and cell organelles of the rat liver against liver protein and hemoglobin as a substrate increases during an initial reaction phase on the first day after 600 R whole body X-irradiation. This is probably a consequence of the degradation of cellular debris. The protein, the protease activity and the free amino acids of the cytoplasm and the cell organelles decrease during the disease phase on day 3 and 4 after irradiation. The protein loss of the liver is therefore not explained by an increased protease activity. The protease activity and the free amino acids are increased in the cytoplasm and the cell organelles during the regeneration phase of the organism between day 15 and 18 after irradiation.


Dynamics of the changes in the tissular levels of cyclic AMP after cobalt-60 gamma-irradiation. The total amounts of cyclic AMP in liver, brain and intestinal mucosa have been measured in rats, at constant intervals, up to 18 days after whole body exposure to either a unique moderate dose (500 rd) or a unique lethal dose (750 rd) of cobalt-60 gamma-radiation. This radiation, even in a lethal dose, was found to induce no significant changes in the hepatic levels of cAMP. In contrast, an abrupt short-lasting increase in the levels of cAMP was observed in brain and intestinal mucosa after a 500-rd-irradiation, and a progressive long-lasting increase in its levels in the intestinal mucosa and, especially, in the brain was found after a 750-rd-irradiation. It is concluded that these organs contain different cAMP systems, which would explain, at least in part, their dissimilar responses to the ionizing rays.


Changes in the composition of milk and rumen contents in cows exposed to a high ambient temperature with controlled feeding. Two pairs of Jersey cows were exposed to either 15 or 30 degrees C air temperature; intake of dried grass was controlled, to be equal at both temperatures. Exposure to 30 degrees C caused increases in rectal temperature and in respiratory rates, and decreases infood intakes in both cows. Milk yield decreased by similar amounts at both temperatures, in association with the decreases in food intakes. The fat and protein content of milk decreased significantly at 30 degrees C; the proportion of shorter chain fatty acids (C6-C14) IN THE milk fat also decreased at 30 degrees C. The proportion of acetic acid in the rumen contents decreased significantly at 30 degrees C, in association with a small decrease in pH. The results indicate that changes in the metabolism of cows occurred at 30 degrees C, independently of changes in food intake.


Brain microvascular hemodynamic responses to induced seizures. Arteriolar diameters and venular erythrocyte velocities in the small pial vessels on the surface of the cat brain were measured by TV methods during induced epileptic seizures through a cranial window. Grand mal seizures maximally dilated arterioles and increased venular erythrocyte velocity up to 400%. High positive correlation existed between changes in CSF hydrogen ion concentration and pial arteriolar diameter, suggesting metabolic regulation of CBF through CSF/interstitial fluid hydrogen ion alterations during the seizure.