Effect of local anesthetics on plasma protein secretion by rat hepatocytes. The effects of some local anesthetics on plasma protein secretion by rat liver slices have been studied and have been compared with those of colchicine. Rat liver slices were pulse-labelled with L-[14C]leucine for 9 min at 37 degrees C, collected on filter paper, washed with non-radioactive leucine and reincubated in the presence or absence of the drug to be tested. The radioactive plasma proteins produced were obtained by immunoprecipitation from either the chase medium or from the washed slices. Chlorpromazine, (3.10(-5) M), dibucaine (10(-5) M), lidocaine (10(-3) M) and procaine (5.10(-5) M) inhibited both the synthesis and secretion of plasma protein but did not affect the uptake of L-leucine into the slices nor the incorporation of phosphate into intracellular nucleotide phosphates or into phospholipids. The inhibition of secretion elicited by these drugs is probably not due to the inhibition of protein synthesis since cycloheximide, when added to the chase medium at a concentration which completely inhibits protein synthesis, did not inhibit plasma protein secretion, while cycloheximide plus procaine did inhibit secretion and also caused a retention of non-secreted plasma proteins within the slices. Unlike colchicine, however, procaine did not cause the retained plasma proteins to accumulate in Golgi-derived secretory vesicles, but showed a more general effect causing a distribution among several cell fractions.


Glycosylation of endogenous proteins through dolichol derivatives in reticulocyte plasma membranes. It has been found that rabbit reticulocyte plasma membranes contain the enzymatic activities responsible for the synthesis of all the polyprenol-bound sugars that are intermediates in the glycosylation of proteins. The final reaction in which an oligosaccharide in transferred from a dolichol pyrophosphate derivative to an endogenous protein was detected in reticulocyte but not in erythrocyte plasma membranes.


CNDO molecular orbital calculations on porphyrins--I. Ground and excited states of porphyrin, divinylporphyrin and tetraphenylporphyrin. Semi-empirical CNDO/2 MO calculations are reported for the ground states of porphyrin, 2,4-divinylporphyrin (DVP), and alpha, beta, gamma, delta-tetraphenylporphyrin (TPP). Results for TPP refer to the conformation with all phenyl groups perpendicular to the porphyrin ring, calculated to be 108 kJ mol-1 more stable than the coplanar conformation. The substituents withdraw electron density where they are attached to the porphyrin ring, increasing selected orbital energies. The vinyl groups also modify the electron population at nitrogen. CNDO/S calculations with extensive configuration interaction are reported for excited states. The lowest singlet states are closely similar in energy and composition for all three molecules, except for an extra state and more complex compositions in DVP above 3 eV. The lowest triplet states of porphyrin and DVP are very similar, while those of TPP are comparable in energy or composition but not both. Experimental data on the excited states are broadly consistent with the calculations, although comparisons for the excited triplets are tentative.


CNDO molecular orbital calculations on porphyrins--II. Ground states of dilithium and disodium porphyrin. CNDO/2 calculations are reported for dilithium and disodium porphyrin. The total energy is calculated as a function of the metal-ring distance for symmetrical (D4h) structures. For dilithium porphyrin, the equilibrium metal-ring distance is 0.87 A and the metal-metal vibrational frequency is 123 cm-1. For disodium porphyrin, the distance is 1.64 A and the frequency is 77 cm -1. Little mixing of metal and porphyrin orbitals takes place; the two lowest unoccupied and the two highest occupied MOs hardly differ from those in porphyrin, but lower MOs are considerably rearranged.


Distribution of 9 trace metals in 17 anatomic sites of dog heart tissue and their classification using pattern recognition. The concentrations (geometric means of 11 determinations) of 9 trace metals in 17 anatomic regions of dog heart tissue and blood vessels were determined. The relationships recognized within the set of trace metal profiles were comparable to those reported earlier for the cardiovascular systems of pig [J. Mol. Cell Cardiol 6, 383 (1974)] and those of beef [Bioinorg, Chem. (in press)]. These included differences in trace metal concentrations that allowed differentiation of the following tissues from each other: (1) ordinary and specialized myocardium from blood vessels and heart valves, (2) blood vessels from heart valves and (3) arterial from venous tissues.


The complexes of adenosine and organocobalamins with palladium (II). The complexes of adenosine, methylcobalamin, adenosylcobalamin and the derivatives of adenosylcobalamin with tetrachloropalladate (II) are described. The compositions of the complexes were established by means of spectrophotometric titration. Depending on the structure of organocobalamins, three types of complexes with tetrachloropalladate (II) are formed. In the case of methylcobalamin, the palladium (II) is coordinated at the "lower" benzimidazole ligand. In adenosylcobalamin, palladium (II) coordinates the "upper" adenosyl ligand. The N-7-position in adenosine ligand and N-3-position in 5,6-dimethylbenzimidazolyribotide are the most probable coordination sites of palladium (II).


A proton magnetic resonance investigation on 1:1 cytidine and guanosine silver(I) complexes. Solid 1:1 silver (I) complexes with cytidine and guanosine have been isolated from aqueous solutions at pH 10. PMR spectra in deuterodimethylsulfoxide-d6 solutions have been measured. Results show that binding sites for cytidine are the nitrogen atom of the NH2 group and N-3. In the Agguanosine complex, pmr data are in agreement with the formation of a chelate ring involving N-7 and O-6. Chemical shift changes of the amino protons show that NH2 is also another binding site.


Inorganic and nutritional aspects of cancer: a conference report. The Inaugural Conference of the International Association of Bioinorganic Scientists (I.A.B.S.) was devoted entirely to inorganic and nutritional aspects of cancer. The reports of twenty-five invited speakers indicate that this area of cancer research has already produced major advances and that further significant progress may be expected to occur in the near future.


[Purification of two beta-D-glycosidases from the digestive juice of Achatina balteata]. Two beta-D-glycosidases have been purified from the digestive juice of Achatina balteata by acetone fractionation, ion exchange chromatography through DEAE-Sephadex A-50, ammonium sulphate fractionation and gel chromatography through Sephadex G-200. The preparations are homogeneous by p/lyacrylamide gel electrophoresis. Both enzymes are highly specific for the beta-D-anomeric configuration of the glycosidic linkage. They hydrolyse lactose, cellobiose and synthetic beta-D-galactosides, -glucosides and -fucosides at a pH optimum of 5,2 to 5,6 and are inactive on alpha-glycosides. The hydrolyzed substrates are recognized by the same catalytic site as shown by mutual competition studies between substrates and competitive inhibition observed with aldonolactones and glycopyranoses such as D-galactose, D-glucose and D-fucose. The different substrates are not hydrolyzed at the same rate by the two enzymes. They also differ by their electrophoretic mobility, their behaviour in gel chromatography and their stability towards pH and heat. The most salient property is the important beta-D-fucosidase activity of the two purified enzymes.


Hydrogen bonding of amino acid side chains to nucleic acid bases. Absorption studies of hydrogen bonding association between nucleic acid bases and amino acid side chains show that association constants can be determined from difference absorption spectra in cyclohexane and chloroform. Association constants for the binding of 9-ethyladenine, 1-cyclohexyluracil and 1-cyclohexylcytosine to side chains of serine, threonine, aspartic acid, lysine, cystéine, methionine and tyrosine are reported. Results obtained in chloroform and cyclohexane are compared.


[Reversible enlargement of proteins in rat liver mitochondria: analysis by polyacrylamide gel electrophoresis]. Intramitochondrial large amplitude protein movements were studied by polyacrylamide gel electrophoresis on the intermembranal fluids of mitochondria which were incubated in presence of movement effectors. The specific and reversible property of this phenomenon was confirmed by this method. Its bilateral nature was observed. The eventuality of a partial inner membrane damage provoked by the synergic action of digitonine and movement effector, was discussed, evaluated and dismissed.


Single-case designs and clinical biofeedback experimentation. Rigorous evaluation of the effects of biofeedback with clinical populations is necessary, but practical problems often preclude utilization of between-groups experimental designs involving large numbers of clients with clinically relevant problems. Single-case experimental designs provide a viable alternative for answering most research questions. In addition, single-case designs possess several distinct advantages for biofeedback research, including a focus on clinical significance, the use of variability as data not error, unique procedures for establishing generality of findings, and an ability to deal with ethical concerns in clinical research. Basic procedures in the use of single-case experimental designs are described and illustrations in clinical biofeedback research are provided.


Cephalic vasomotor feedback in the modification of migraine headache. The effect of cephalic vasomotor response (CVMR) and frontalis electromyographic (EMG) feedback on control of temporal arterial vasoconstriction and frontalis muscle activity in migraine and muscle contraction headache patients was investigated. A single subject multiple baseline design (across subjects and responses) was introduced to evaluate (1) patterning in the two physiological systems and (2) the effects of CVMR and EMG feedback on headache activity. The data indicated that (a) all four patients demonstrated an ability to control CVMR activity during CVMR feedback and EMG during EMG feedback, (b) idiosyncratic patterns of physiological activity emerge during feedback training, and (c) learned control of the pain mechanism for muscle contraction and migraine headaches was related to reduced frequency and duration of these headaches.


Independent biofeedback self-regulation of EEG alpha and skin resistance. Skin resistance and EEG alpha were recorded concurrently during alpha biofeedback, in which the participant attempted to control alpha, and during skin resistance biofeedback, in which the participant attempted to control skin resistance. Alpha production changed significantly (p less than .001) during alpha biofeedback, indicating successful self-regulation of alpha, but did not change significantly during skin resistance biofeedback. Similarly, skin resistance changed significantly (p less than .001) during skin resistance biofeedback but did not change significantly during alpha biofeedback. The results show independent control of alpha and skin resistance, and may reflect independent self-regulation of cognitive and somatic tension-relaxation systems.


Locus of control and frontal electromyographic response training. Forty-eight normal subjects from a college population, representing extreme internal and external orientations on a locus of control scale, were provided an auditory signal in a laboratory relaxation setting. For one group (feedback) the pitch of the signal varied as a function of frontal electromyographic (EMG) levels, while for another group (control) the pitch was constant. The feedback subjects acquired lower EMG potentials than did the control subjects, and the internal subjects in the feedback condition acquired lower levels than did the external subjects. In the control condition, no consistent differences in EMG levels between internal and external subjects were obtained. These results were stable across two replications, three ethnically distinct groups, and both sexes. Additional measures designed to reflect the effects of the frontal EMG training as a generalized relaxation technique for this population, including finger temperatures and a variety of postexperiment queswtionnaire ratings of relaxation, yielded negative results. Tests of other predictions from the locus of control construct are also discussed.


The use of EMG feedback in the treatment of a severe case of blepharospasm. In this case report, a 50-year-old female with a chronic blepharospasm (spasmodic winking) around both eyes was treated with 17 sessions of electromyographic (EMG) feedback. EMG level and spasm frequency were monitored during baseline, placebo, and feedback treatment sessions. There was a marked decrease in both EMG level and spasm frequency, which generalized to her everyday life. Improvement was maintained at 4-month follow-up.


[A new method for synthesis of some nucleoside 5'-phosphonate esters]. A new method for synthesis of nucleoside-5'-phosphonates containing a reactive halogen atom in the phosphonate residue has been developed. In order to achieve selective inhibition of individual enzymes and to elucidate the structure of their active sites, the synthesis of 5-'chloromethyl-, 5'-(beta-bromoethyl)-and 5'-(N-chloroacetylaminomethyl)-phosphonate esters of adenosine and previously unknown analogous derivatives of uridine have been carried out. The method described may also be used to synthesize 5'-phosphonate esters of nucleosides, which contain radioactive labels.


[Regeneration of rhodopsin in marine teleost fishes in the presence of exogenic of 11-cis-and all trans-retinals]. Regeneration of rhodopsin of the sea perch (Sebastodes schlegeli) and walleye pollock (Theragra chalcogramma) was studied in different preparations of eye after the addition of 11-cis- and all trans-retinals and at the expense of endogenic sources. It was established that the regeneration of rhodopsin in the eye cup, homogenate of retina and rod outer segments (ROS) at the expense of endogenic sources was extremely low and it was slightly forced by the addition of the pigment epithelium to the last two preparations. The binding degree of 11-cis retinal of walleye pollock ROS decreased with the increase of temperature of the incubation mixture and the increase of duration of storage of ROS at the temperature--10 degrees. Partial removing of lipids by hexane decreased the percentage of regeneration of the ROS preparation; on the other hand, the peroxidation of lipids practically did not affect the regenerative ability of fresh-obtained preparations. After solubilization of opsin by digitonin and sodium cholate, 40- and 50%-decreases of binding of 11-cis retinal were observed respectively. The digestion of ROS by papain, which caused no changes in the spectral properties of dark preparations, completely eliminated the regenerative ability of ROS. Regeneration of ROS at the presence of all trans-retinal proceeded at a very low speed. The specificity of the process of regeneration of rhodopsin in fishes is discussed.


[Study of the topography of the nitrogenase active center by the electron microscopy method with the use of the electron density labels]. The electron microscopy method has been used for studying the topography of the active centre of the nitrogenase in combination with the method of electron density labels. The active centre has been shown to place on the nitrogenase macromolecule asymmetrically. The non-heme iron atoms of the nitrogenase active centre have been regularly packed and located on the macromolecule as a quadrangular cluster closely to the surface of subunits. Two free sulfhydryl groups of the ATP-site of the nitrogenase active centre are in close proximity to the cluster. ATP-site of the nitrogenase active centre containing these groups is located on the Fe-enzyme, while the main part of the iron-containing cluster is located on the Mo-Fe-enzyme.


[Two simple methods for isolation of DNA from various sources using cetavlon]. Two general methods for the isolation of DNA from various sources based on the use of cetyltrimethylammonium bromide (cetavlon, CTA-Br) are described. Cetavlon is a strong cationic detergent precipitating DNA from diluted salt solutions. Cells are lysed and cellular components are dissolved in the presence of cetavlon, 5 M urea, 0.1 M EDTA and 2 M NaCl (KCl). In the first method pure DNA is precipitated in the form of CTA-salt by direct dilution of the lysate to bring the concentration of NaCl (KCl) down to 0.5 M after the removal of the main part of proteins by deproteinization with chloroform. In the first method pure DNA is precipitated in the form of CTA-salt by direct dilution of the lysate to bring the concentration of NaCl (KCl) down to 0.5 M after the removal of the main part of proteins by deproteinization with chloroform. In the second method DNA is purified on the hydroxyapatite column after cell lysis and the removal of cell debris by centrifugation. Both methods are suitable for rapid isolation of pure DNA from various sources with recovery about 80% and average molecular weight 20-10(6) and higher without use of ribonuclease, pronase and amylase.


[Reversibility of glycolysis in leaves of C4-plants]. A conversion of the reaction of two cytoplasmic glycolysis enzymes, phosphoglycerate mutase and phosphopyruvate hydratase, is necessary for sucrose synthesis from pyruvate in leaves of C4-plants in the light, when phosphoenolpyruvate synthesis from pyruvate and phosphoglycerate reduction can be carried out by chloroplasts. Leaves of C4-plants differ from those of C3-plants in a higher activity of cytoplasmic glycolysis enzymes, which are distributed irregularly in two assimilatory tissues. The ratio of pyruvate kinase and enolase reaction activities is high in parenchyma linings of vascular fascicles (where mitochondria are concentrated), and it is low in mesophyl tissue, where phosphoglucerate in equilibrium phosphoenolpyruvate reaction is included into photosynthetic metabolism. The data obtained on isolated mesophyl protoplasts have shown that the reaction equilibrium is sharply shifted into the direction of phosphoenolpyruvate formation from phosphoglycerate. However, the incorporation of 14C into sugars is not completely inhibited in the atmosphere of N2-A possibility of incorporation of tri-carbon fragments into sugars in photosynthesizing leaves via conversion of enolase reaction and via alternative pathways is discussed.


[Comparative study of light-harvesting complexes of purple photosynthetic bacteria Chromatium minutissimum and Rhodopseudomonas palustris]. Light-harvesting pigment-lipoprotein complexes from sulfur (Chromatium minutissimum) and non-sulfur (Rhodopseudomonas palustris) purple bacteria are isolated and comparatively studied. Electron microscopy was used for determination of the complex size, different methods were employed to estimate their molecular weights and chemical composition. Two small proteins are found in each complex, their molecular weight, molar ratio and their content per complex being studied. Amino acid composition and N-terminal amino acids are determined for both proteins of light-harvesting complex from Chromatium minutissimum. Some common characteristics of the molecular organization of light-harvesting complexes in purple bacteria are discussed.


[On the changes in alpha-chymotrypsin stability after its modification by polyelectrolytes]. Reversible thermal denaturation of alpha-chymotrypsin, its electrostatic complexes with carboxyl-containing polymers and the enzyme covalently bound with those polymers were studied. It was shown that the enzyme stability is affected by matrix, which manifests itself in a simultaneous decrease in enthalpy and enthropy of the reversible denaturation process and a simultaneous decrease in activation enthalpy and enthropy of denaturation. Modification and complexing of chymotrypsin with polymers has practically no effect on the activation parameters of renaturation. Differences in the original states of alpha-chymotrypsin and its derivatives and similarity of their activated states are proposed. The formation of ionic complexes of enzyme or covalent binding to polymers results in alteration of the protein native state similar to the denaturated state.


[Active transport of riboflavin in the yeast Pichia guilliermondii. Detection and some properties of the cryptic riboflavin permease]. In contrast to cells and protoplasts of the wild strain intact cells and protoplasts of riboflavin (RF)-deficient mutants of Pichia guilliermondii yeast possessing multiple sensitivity to antibiotics and antimetabolites were found capable to accomplish active transport of RF. The accumulation of RF against concentration gradient was energized by endogenous energy sources and was strongly depressed by uncouplers of oxidative phosphorylation and by inhibitors of respiration. RF transport was also blocked by the agents which destroy the permeability barrier and by sucrose. Cyclohemide did not inhibit the transport of vitamin B2. Uptake of RF depends on temperature and pH of the incubation mixture. RF permease possessed rather stringent substrate specificity and did not catalyze transport of FMN and FAD. RF uptake in two strains tested, MS1-3 and MS1, followed saturation kinetics (Km = 0.17 mM and 2.0 mM, respectively) and was not connected with RF auxotrophy. The ability for exogenous RF uptake was controlled by recessive allele. Restoration of normal resistance to antibiotics and antimetabolites was accompanied by a decrease in the permease affinity for substrate.


[Characteristics of photosystem I from grana thylakoids and from stroma lamellae]. Photochemical and spectral properties of photosystem I particles isolated from grana thylakoids and stroma lamellae of chloroplasts of higher plants are studied. The similarity of P700 content in these particles and the same dependence of P700+ reduction on temperature and the time course of variable fluorescence from artificial electron donors and acceptors indicate on the same type of reaction center for both photosystems I. Stroma particles have a higher rate of dark relaxation of variable fluorescence and a higher rate of dark reduction of P700+ at room temperature, than grana particles. Moreover, on the basis of data on low temperature fluorescence spectra, the stroma particles contain less shortwave chlorophyll a forms than grana particles. Thus, photosystem I from grana thylakoids and from stroma lamellae have the same type of reaction centers and can differ only by their nearest environment.


[Synthesis and some properties of immobilized transketolase]. A covalent binding of transketolase to bromo-cyanogen-activated Sepharose 4B at the pH value of the maximum activity and stability of the enzyme equal to 7,6 has been carried out. It has been shown that upon immobilization the enzyme retains up to 50% of its specific activity. The stability of the immobilized transketolase increases, depending on the degree of template activation 5- to 9-fold at 4 degrees C and 5- --20-fold at 50 degrees C. The value of the activity pH-optimum remains almost unchanged. In the presence of Mg2+ the pH-dependence curve somewhat broadens towards higher alkalinity whereas in the presence of Ca2+ it becomes less steep as compared to enzyme solution. The apparent Michaelis constant for substrates (pentose phosphates mixture) does not differ from Km for a free enzyme.


[The problem of structural heterogeneity of brain prealbumin]. The investigation of structural heterogeneity of rat brain prealbumine (BTB-protein) has been carried out. BTB-protein migrates in disc electrophoresis in 7.5% and 10% polyacrylamide gel with the "witness" front of bromthemol blue (BTB). The protein dissociated in three components in 8M urea. Three components with the molecular weight 14500, 8000 and 6900 daltones were found by disc electrophoresis of BTB-protein in 0.1% SDS-Na. Glycine was shown to be N-terminal amino acid of this BTB-protein complex.


[Fractionation of chromatin in acrylamide gel with immobilized non-histone proteins and DNA]. Liver and kidney chromatin and DNA were fractionated in acrylamide columns with immobilized readily extracted non-histone chromosomal proteins (RE-NHCP). Chromatin was fractionated in two fractions on the column with RE-NHCP, one of the fractions is sorbing and has a poor protein contents, as compared to the initial chromatin preparation. Fractionation of chromatin in two fractions (sorbing and non-sorbing) was also observed under its chromatography in the column with immobilized DNA. Both chromatin fractions are stripped in the protein content after the elution, which is probably due to the transfer of some proteins from chromatin to immobilized DNA. Chromatography of DNA on gel with homologous RE-NHCP also results in DNA fractionation into sorbing and non-sorbing fractions. The data obtained suggest the irregularity of the distribution and the restriction of "binding sites" for exogenous homologous and heterologous RE-NHCP and of the number of chromatin proteins, which are capable of additional binding with exogenous homologous DNA.


[Study of the reversible inactivation of the cyanide-resistant pathway of electron transfer in mitochondria of the yeast Candida lipolytica]. The study of reversible inactivation process of alternative pathway of electron transfer in cyanide-resistant mitochondria of C. lipolytica yeast was carried out. The appearance of sensitivity of respiration of cyanide-resistant mitochondria to cyanide and lowering of sensitivity of substrate oxidation to benzohydroxamic acid (the inhibitor of electron transfer along the alternative pathway) during the incubation was observed. The increase of temperature and the presence of magnesium ions in the incubation medium accelerates this process. The loss of cyanide resistance of respiration by mitochondria is not practically followed by the decrease of NADH-and alpha-glycerophosphatoxidase activity. Reactivation of cyanide resistance of respiration in incubated mitochondria is reached during washing them with the medium containing EDTA. The addition of magnesium ions into the washing medium prevents the reactivation process. On the basis of data obtained it is concluded that the relation between the respiratory chain and alternative oxidase is regulated by magnesium.


Individual differences in human circadian rhythms. Research into individual differences in circadian rhythms is reviewed, particularly morningness-eveningness. It was hypothesised that extraverts would be inclined towards eveningness and introverts towards morningness. Forty-eight subjects took regularly their oral temperature. Peak times were identified from smoothed temperature curves. Results showed that extraverts had a peak time insignificantly later than introverts. Re-grouping of the data into the morningness-eveningness dimension, based upon the results of a self assessment questionnaire, showed that evening types had significantly later peak times than morning types. Morningness-eveningness was not significantly ocrrelated with extraversion-introversion, although there was a trend. No significant differences were found for sleep lengths with either groupings, or for sleep-wake habits within extraversion-introversion. Morning types retired and arose significantly earlier than evening types. Although sleep-wake habits and extraversion-introversion help to determine peak times there are other contributory factors to peak time which appear to be partly covered by the questionnaire.


Effects of afternoon naps on physiological variables performance and self-reported activation. Fluctuations in physiological variables resulting from naps and the relationship of these to previously studies changes in performance and subjective activation associated with napping were examined. The subjects were eighteen healthy male university students who habitually slept 1/2-2 hr in the afternoon. Measurements were obtained of our physiological variables, from a continuous 10-min auditory reaction time task and two factors of an Activation. Deactivation Adjective Checklist 20 min before and after a control condition and two electroencephalographically recorded afternoons of sleep. The experimental conditions comprised a 2-hr period of wakefulness, a 1/2 hr nap from 4.35-5.05 p.m., and a 2-hr nap from 3.05-5.05 p.m. Following each sleep treatment, when compared with the control condition, there were statistically significant shifts of improved reaction time performance, and elevated activation as reflected by the two self-report scales, inceased EEG frequency, heart rate, and electrodermal responses. The shifts of increased behavioral efficiency, subjective and physiological activation were approximately equivalent in extent between 2-hr and 1/2-hr naps. These findings indicate that besides the previously reported facilitation by naps of performance and mood, physiological activation is increased following accustomed episodes of afternoon sleep.


Instrumental conditioning of human heart rate during free and controlled respiration. The effect of respiratory constraint on heart rate control was assessed in a biofeedback situation with feedback consisting of changes in both illumination level and intensity of pre-recorded baby's cry. Subjects were reinforced for alternately increasing and decreasing heart rate on each of seven days during which respiration was unconstrained (Phase 1). This phase was followed by eight days when respiration was constrained during training sessions with a control respirator (Phase 2). Seven additional days of training followed in the unconstrained situation (Phase 3). Results indicate that the control of heart rate in biofeedback situations is very closely related to respiratory and other somatic activity. The implication of these findings for the field of visceral control is discussed.


Visual evoked response correlates of cerebral specialization after human commissurotomy. Visual evoked responses (VERS) were recorded from commissurotomy patients and normal subjects in order to investigate the electrophysiological correlates of cerebral lateralization and independent hemispheric processing. A verbal task consisted of detecting rhyming words and a spatial task consisted of comparing matching shapes. Stimuli were delivered, by means of a computer graphic display, into the right visual field, the left visual field, or both visual fields. Behavioral results and evoked response waveforms showed lateralization for verbal processing in the left hemisphere for the patient group. Analysis of variance of product moment correlation coefficients between VER waveforms indicated significant differences between unilateral and bilateral stimulation for both patients and normals. Commissurotomy and normal VERs showed similar patterns of correlation when verbal stimuli were delivered to the left hemisphere, but differed during right hemisphere stimulation. The results are discussed in terms of VER correlates of visual-verbal processing.


Dynamic evaluation of the viscoelastic properties of a biomedical polymer (biomer). This paper deals with the experimental determination of the dynamic constants, storage and loss moduli of a viscoelastic material currently used as membranes in the artificial heart or other types of cardiac bypass pumps. A brief discussion of the viscoelastic theory is given, starting with the relaxation and creep function leading to the determination of the stress-strain relationship in integral equation form. It is shown that when dealing with periodical strain histories, the integral equation form may be reduced to a complex form. The complex moduli are used to describe the stress-strain relationship. The "Hysteresis Loop" method was used in this investigation to experimentally determine the material constants. This method was found to be convenient and direct for the experimental evaluation of the constants. These dynamic constants may then be used in a computer analysis, i.e., finite elements analysis, to determine the stress distribution in the membrane when subjected to loads or deformations.


Diffusion of mercury in HgSn8 (gamma2 phase). The tracer diffusion coefficients of mercury in a Sn-Hg alloy (Sn 82.6 and Hg 17.4 wt.%; HgSn8 (gamma2 phase)2.6 and Hg 17.4 wt.%; HgSn8 [gamma2 phase]) were measured by the residual activity method at temperatures ranging from 35.5 to 95 degrees C. The Arrhenius equation for the mercury tracer was found to be Dv=2.10 X 10(-3) exp (-8.96 X 10(3)/RT) cm2/sec. The diffusivity of mercury in the three phases, the gamma (Ag3Sn), gamma1 (Ag2Hg3) and gamma2 (HgSn8) phase, that coexist in silver-tin dental amalgam have now been determined. Mercury diffuses fastest in gamma2 phase and slowest in gamma phase.


Mechanical property changes of barium titanate (ceramic) after in vivo and in vitro aging. Since barium titanate (BaTi03) can be made piezoelectric, it may be used to substitute hard tissues directly. As a first step in testing this concept, a series of in vivo and in vitro aging and biocompatibility studies were performed. The mean compressive strength of samples implanted subcutaneously in the backs of rabbits decreased to 138 MPa after 20 weeks from a control value of 281 MPa. Similar, though less drastic losses of strength were seen when specimens were aged in distilled water (182 MPa at 28 weeks) and Ringer's solution (159 MPa at 28 weeks). The most rapid decrease of strength in all cases was seen prior to 4 weeks. Thereafter, the decrease was much slower. Histological evaluation of the tissue surrounding the implant revealed a thin fibrous capsule and no evidence of tissue inflammation.


Non-polarographic blood gas analysis. II. In vivo evaluation of gas chromatograph system. Evaluation of a new system, based on gas chromatography, providing arterial blood gas tensions without requiring drawn blood samples is continued in an animal model. A series of in vivo dog experiments is discussed evaluating flow dependence and other performance characteristics. Results confirm the laboratory bench performance reported earlier; clinical trials are now indicated.


Immunologic evaluation of rheumatoid arthritis and therapy with levamisole. The haemolytic complement activity and the complement components C3, C4 and  C1q were significantly increased in the sera of 43 patients with classic or definite rheumatoid arthritis. The increased complement activity was fairly well correlated with an increased sedimentation rate, increased IgG levels and rheumatoid factor positivity. The E-rosette formation of T-lymphocytes measured in 16 rheumatoid arthritis patients was significantly depressed. These 16 patients were treated with levamisole 50 mg t.i.d. Four patients discontinued treatment because of side-effects. The remaining 12 patients were re-examined clinically and immunologically after a mean treatment period of 3.9 (range : 2.5-8) months. A significant reduction in haemolytic complement activity, C3, IgG and sedimentation rate and a significant increase in E-rosette forming cells were observed, and these were accompanied by a significant clinical improvement. These findings are discussed in view of the new concept that the basic defect in rheumatoid arthritis could be a disturbance of the interaction of T-and B-cells and faulty suppressor T-cells. According to this hypothesis, levamisole restores cell-mediated immune reactivity, thereby affecting the natural course of rheumatoid arthritis.


Weight and metabolic changes induced by low carbohydrate-high fat diets in man and in rat. Weight loss and potential toxicity of low carbohydrate-high fat diets were examined in 8 volunteer medical students given either a high fat diet or a high carbohydrate diet for 15 days, as well as in 36 Sprague-Dawley rats fed for 5 weeks a series of low carbohydrate diets (less than 1%), varying in protein and lipid proportions. A weight loss occurred with the low carbohydrate-high fat diets; serum cholesterol level increased in both man and rat; plasma triglycerides rose in man. In rat, we found an increase in hepatic lipid levels as in plasma ketone and non-esterified fatty acid concentrations. These effects seemed to be related to the increase in lipid intake rather than the lack of carbohydrates.


Selective chemotherapy for advanced murine L 1210 leukemia by combination of 2' deoxycytidine and lethal doses of cytosine-arabinoside. Oral administration of deoxycytidine simultaneously with intraperitoneal injections of cytosine arabinoside reduced toxicosis preventing drug death of mice with L1210 leukemia. These animals developed a marked antitumor effect having the median survival time (MST) considerably longer than that of untreated animals or of those receiving either of these drugs alone. At the optimal dose schedule 23% of mice survived 60 days. Under similar conditions mice with myeloid Graffi leukemia showed no antitumor response.


The influence of alpha thioglycerol on erythropoiesis in fetal mouse liver cell cultures. alpha-Thioglycerol has been shown to increase hemoglobin synthesis in suspension cultures of fetal mouse liver cells. The mechanism of this effect is unknown but appears to be directly on S-phase cells increasing their sensitivity to erythropoietin. alpha-Thioglycerol inhibits heme synthesis when S-phase cells have been removed by prior treatment with hydroxyurea. The stimulatory or inhibitory effects of thiols depending on the proportion of cells in S-phase suggests that extreme caution should be used when interpreting cell kinetic studies of cultured cells if thiols are present in the cultures.


Ribosomal and transfer RNA contents of the normal and pathologic human thyroid gland. One hundred and seventy seven pieces of normal or pathologic thyroid tissue from 17 patients were assayed for rRNA, tRNA and DNA content. The tRNA/DNA and rRNA/DNA ratios in pathologic tissue were statistically compared with the same ratios in normal tissue. In toxic adenoma (5 cases) and anoplastic cancer (2 cases), both ratios were increased. In cold nodules (9 cases), there was in increase of the tRNA/DNA ratio only in 1 case, of the rRNA/DNA ratio only in 4 cases, and of both ratios in 3 cases. In one case of a cold nodule in a Basedow's disease gland, there was no modification of these ratios. In Basedow's disease (3 cases), there was an increase of rRNA/DNA ratio only in one case.


Plasma cell acid phosphatase, a discriminative test for benign and malignant monoclonal gammopathies. Acid phosphatase activity estimated cytochemically is markedly increased in myeloma plasma cells compared to that found in normal plasma cells, polyclonal plasma-cytoses and most interestingly in the non-myelomatous monoclonal dysglobulinaemias. In the differential diagnosis of this last group the test has a useful role.


A theory of fluorescence polarization decay in membranes. Decay of fluorescence polarization after an impulsive excitation is correlated with wobbling motion of fluorescent molecules in membranes. The motion is characterized by two parameters, a "wobbling diffusion constant" and a "degree of orientational constraint" both of which can be determined directly from experimentally obtained decay. Detailed discussion, including theoretically calculated time-courses of polarization decay, is given for several types of molecules embedded in lipid bilayers; these types cover a large part of fluorescent probes available at present. The theory is useful for the analysis of fluorescence polarization decay in any system where the orientation of fluorophore is restricted by the surrounding structure.


Osmotic correction to elastic area compressibility measurements on red cell membrane. In a recent article (Biophys. J. 16:585, 1976), we reported measurements of the elastic area compressibility modulus or red cell membranes using micropipette aspiration on osmotically preswollen red cells. Subsequently, we have analyzed the effects of osmotic and hydrostatic pressure driving forces across the cell membrane in conjuction with the mass conservation equation; we find that the change in cell volume due to the reversible movement of water out of the cell can produce one-third of the movement of the cell projection in the pipette tip. Since the actual volume changes is too small to measure directly (about 1% of the total cell volume), we have used an indirect experimental method to provide critical evaluation of the analysis of cell volume change versus applied pressure; this is based on the model that the change in cell volume is inversely proportional to the cellular osmotic strength. We have increased the cellular cation concentration with a drug, nystatin, and measured the elastic area compressibility modulus corrected for osmotic volume changes as a function of cellular osmotic strength. We find that the corrected elastic are compressibility modulus is independent of cellular osmotic strength, which supports the model and calculated correction for the osmotic effect. The elastic area compressibility modulus is 450 dyn/cm at 25 degrees C instead of 300 dyn/cm, determined previously.


Fluctuations in tension during contraction of single muscle fibers. We have searched for fluctuations in the steady-state tension developed by stimulated single muscle fibers. Such tension "noise" is expected to be present as a result of the statistical fluctuations in the number and/or state of myosin cross-bridges interacting with thin filament sites at any time. A sensitive electro-optical tension transducer capable of resolving the expected fluctuations in magnitude and frequency was constructed to search for the fluctuations. The noise was analyzed by computing the power spectra and amplitude of stochastic fluctuations in the photomultiplier counting rate, which was made proportional to muscle force. The optical system and electronic instrumentation together with the minicomputer software are described. Tensions were measured in single skinned glycerinated rabbit psoas muscle fibers in rigor and during contraction and relaxation. The results indicate the presence of fluctuations in contracting muscles and a complete absence of tension noise in eith rigor or relaxation. Also, a numerical method was developed to simulate the power spectra and amplitude of fluctuations, given the rate constants for association and dissociation of the cross-bridges and actin. The simulated power spectra and the frequency distributions observed experimentally are similar.


A phase-shift fluorometer using a laser and a transverse electrooptic modulator for subnanosecond lifetime measurements. We described a simple phase-shift fluorometer using continuous laser excitation. The laser enables the use of a transverse mode electrooptic modulator with a half-wave retardation voltage of about 200 V (in contrast to many kilovolts of longitudinal modulators) at frequencies up to 100 MHz. The modulated fluorescence signal is detected, after passing through a double monochromator, by a photomultiplier tube feeding a radio frequency (RF) tuned amplifier. THE RF phase is then determined by phase-sensitive detection using a double balanced mixer with the reference obtained from a PIN photodiode-turned amplifier combination which detects light split off from the main exciting beam. The laser and double monochromator allow the observation of modulated Raman solvent and Rayleigh scatterin, which are convenient for determining the zero reference phase.


Resonance Raman kinetic spectroscopy of bacteriorhodopsin on the microsecond time scale. Using a rotating disk with a slit of variable width, a continuous wave argon ion laser, and an Optical Multichannel Analyzer for detection, a new technique is reported which should, in principle, be capable of recording resonance Raman spectra with time resolution of 100 ns. The resonance Raman spectra of the intermediates of the photosynthetic cycle of bacteriorhodopsin are recorded on the microsecond time scale. Both the kinetic results and the resonance enhancement profile suggest that deprotonation results in an intermediate preceding bM412 that has an optical absorption maximum at a wavelength longer than that of bM412.


Electronic structure of polyenes related to the visual chromophore. A simple model for the observed band shapes. A model is presented which attributes the widths of absorption bands in carotenoids to conformational disorder induced by the beta-ionylidene moiety. With reasonable parameter choices, the model gives a good quantitative fit to the spectra observed for four carotenoids and at the same time accounts for the lack of structure in the long-wavelength absorption of retinal.


Triplet state energy transfer in several proteins. Energy transfer between excited triplet states of aromatic amino acid residues was observed at 1.4 degrees K. The distance necessary for energy transfer between monomeric tyrosine and tryptophan residues was determined to be roughly 63 A. Total phosphorescence decay rate constants for several proteins were determined while emission corresponding to tyrosine and tryptophan residues was monitored. The observed decay rate constants are interpreted in terms of intramolecular interactions of the polypeptide residues.


Application of cyanide-metabolizing enzymes to environmental control; enzyme thermistor assay of cyanide using immobilized rhodanese and injectase. The application of the enzyme thermistor in the analysis of cyanide in standard solutions as well as in blast furnace waste water is described. The heat signal is generated in the conversion of cyanide, catalyzed by the immobilized enzymes rhodanese (E.C. 2.8.1.1) and injectase (E.C. 4.4.19). Using the combination of cyanide-metabolizing enzymes and the enzyme thermistor unit, assays down to 20 microM cyanide can be carried out. Linear relationships were obtained at 20-600 microM cyanide for injectase and 20-1000 microM for rhodanese. The stability at 27 degrees C of the heat response was initially decreased, but soon stabilized at about 80% of the initial value and remained so for at least 200 hr. The technique was easily adapted to continuous analysis, applicable to environmental control (e.g., a "cyanide guard") with a response time at present within 2-3 min after a sudden change in cyanide concentration has appeared.


Application of immobilized chymotrypsin in a multistage fluidized-bed reactor. The stereospecific hydrolysis of D,L-phenylalanine methylester with immobilized alpha-chymotrypsin was carried out as a model reaction for the racemate resolution of aromatic amino acids in a five staged fluidized-bed reactor (FBR). Owing to ester hydrolysis, a pH shift occurred along the reactor. Because of the pH-dependent enzyme activity a particular longitudinal pH profile had to be enforced by a proper entrance pH in order to gain an optimum conversion. In the FBR with optimum pH profile, higher conversions were achieved than in a continuous stirred tank reactor (CSTR) at the pH optimum and at the same contact time. By the application of a proton balance and the results of kinetic measurements a model was developed for the prediction of the optimum longitudinal pH profile with regard to the maximum conversion.


Anomalies of the aortic arch system.

Anomalies of the aortic arch system. Abnormalities in the development of the aortic arch system may yield anomalies either of the definitive aortic arch and its branches or of pulmonary arterial origin. Anomalies of the aortic arch and its branches may cause compression of the trachea and esophagus or simply yield anatomic patterns which vary from normal without causing specific symptoms. Anomalies of pulmonary arterial origin usually take the form of origin of one or both pulmonary arteries either from the aorta or the innominate artery. The various anomalies are related to loss of specific segments of the primitive aortic arch system.


Dyssegmental dwarfism: a new syndrome of lethal dwarfism. Dyssegmental dwarfism is an autosomal, recessively inherited, lethal, generalized chondrodysplasia characterized by micromelia, cleft palate, and variable limited mobility at the elbow, wrist, hip, knee, and ankle joints and, in some cases, by occipital encephalocele, inguinal hernia, hydronephrosis, hydrocephalus, and patent ductus arteriosus. Roentgenographically, there is a marked variation in the size of all vertebrae with some anterior wedging, coronal clefts, and lack of caudal interpediculate widening. In addition, there are short, broad tubular bones with metaphyseal widening, variable bowing of the tibia, fistula, femur, radius, and minimally the ulna. In the feet, the talus and calcaneus are poorly modeled, and the 1st metatarsal and 1st proximal phalanx are enlarged. The striking similarities among these cases, as well as the others in the literature, argue strongly for their being a common defect in embryogenesis. However, there is also evidence of heterogeneity. Our case reported here has distinct hypoplasia of the scapulae, absence of carpal ossification centers, and lack of flaring of the ilia, whereas the other cases show well-developed scapulas, accelerated carpal bone maturation, and a wide-flared ilia.


Embryologic pathogenesis of renal agenesis associated with cervical vertebral anomalies (Klippel-Feil phenotype). Existing embryologic data suggest that the blastema of the cervical vertebrae, scapulae, and the genitourinary system have an intimate spatial relationship at the end of the 4th or beginning of the 5th week of fetal life. An alteration in this region can affect the cervical vertebrae and scapulae directly, and the genitourologic changes are mediated indirectly through the inductive capacity of the pronephric duct. The genitourinary malformation documented in patients with a specified Klippel-Feil phenotype support such an embryologic pathogenesis. Urologic pathology, in both sexes, is consistent with partial or absent induction of ureteral bud formation, and genital pathology in the female reflects partial or complete failure of müllerian duct development. These data also suggest a more frequent bilateral occurrence of these anomalies; a phenomenon that, in its most severe form, would result in bilateral renal agenesis, as illustrated by the stillborn presented in this paper.


Selective increase of potassium permeability in red blood cells exposed to acetylphenylhydrazine. Normal human red blood cells, when exposed briefly to acetylphenylhydrazine (APH), acquire Heinz bodies and a propensity for net ion and water loss upon subsequent incubation in an APH-free medium of physiologic sodium and potassium (K) content. The cells can be protected from APH damage by previous deoxygenation. The ion and water loss depend on the presence of a K gradient from cell to medium. In contradistinction to some other types of membrane perturbation in which K permeability is increased, the APH effect is not dependent on calcium. The meaning of these observations is discussed in relation to the vulnerability of the K permeability barrier.


Effect of phagocytosis on the reduced soluble sulfhydryl content of human granulocytes. The role of reduced glutathione in relation to hexose monophosphate shunt activity and peroxide detoxification has been well established in human erythrocytes. Less is known about the content of reduced glutathione in phagocytic leukocytes and the changes that occur during functional activity. We have measured the reduced sulfhydryl content of normal resting human granulocytes and of cells isolated from a patient with chronic granulomatous disease. Normal cells and those from the patient with chronic granulomatous disease contained similar concentrations of reduced sulfhydryls. Stimulation of a phagocytic response by incubation with opsonized zymosan particles resulted in prompt and nearly complete depletion of intracellular glutathione from normal granulocytes. This fall in reduced glutathione concentration was dependent on the phagocytic load. Exposure of chronic granulomatous disease granulocytes to a similar phagocytic load resulted in a slower and less complete fall in reduced glutathione. In normal cells, those from the chronic granulomatous disease patient, and those from an obligate carrier of the disease, the decrement in reduced glutathione during phagocytosis was correlated with oxidation of 14C-1-glucose and 14C-formate, nitroblue tetrazolium reduction, and the chemiluminescence phenomenon.


Circulating erythropoietic precursors assessed in culture: characterization in normal men and patients with hemoglobinopathies. Circulating erythropoietic precursors in normal men and patients with hemoglobinopathies were characterized in culture. Blood mononuclear cells harvested with a modification of the Ficoll-Isopaque technique were cultured in methylcellulose for 14 days. The majority of erythropoietic colonies consisted of several subcolonies assuming the morphology of erythropoietic "bursts" described in murine marrow cultures. Time course studied of colony formation from marrow and blood nucleated cells confirmed that the circulating erythropoietic precursors represented only early stages of development. Peak sedimentation velocity of the circulating precursors analyzed using a Staput apparatus averaged 5.31 mm/hr and corresponded with that of the early erythropoietic precursors in human marrow. One ml of blood yielded an average of 153 colonies in normal men and 785 colonies in patients with hemoglobinopathies. No correlation was observed between colony formation and reticulocyte indices of individual patients. Examination of the proliferative state of the erythropoietic precursors using high specific activity tritium-labeled thymidine revealed that almost none of the cells in normal men or patients with hemoglobinopathies were in the DNA synthetic phase.


Effect of protein deprivation on erythropoiesis. The effects of protein deprivation on erythropoietin (Ep) production were studied. The posthypoxia plasma Ep levels of rats fed a protein-free diet for only 1 day prior to being exposed to 0.5 atmosphere for 7 hr were significantly lower than those of comparably hypoxic rats maintained on a normal diet. The postthypoxia plasma Ep levels were even lower in rats kept on protein-depleted diets for longer periods of time. Rats fed diets with 0.5%, 5% or 12% protein content for 6 days had lower posthypoxia plasma Ep levels than those fed a normal diet (20% protein content). When a single protein meal was force-fed to protein-deprived rats 0-4 hr after initiating the exposure to hypoxia, the posthypoxia plasma Ep levels were significantly higher than in protein-deprived rats that were fed water or dextrose. The posthypoxia plasma Ep titers of protein-deprived rats fed protein 4-8 hr prior to exposure to hypoxia did not differ significantly from those of protein-deprived rats. Although the posthypoxia plasma Ep levels of protein-deprived rats fed a hemolysate containing 0.8 g of hemoglobin 4 hr after beginning hypoxia were greater than those of protein-deprived rats fed only water, the rate of oxygen consumption in these two groups did not differ. We conclude that, in addition to its response to the availability of oxygen, Ep production is infl,enced by the availability of amino acids.


Effect of storage on normal neutrophils collected by discontinuous-flow centrifugation leukapheresis. Storage limits for granulocytes have not been defined. The purpose of this study was to determine these limits for neutrophils collected by discontinuous-flow centrifugation and stored at 4 degrees-6 degrees C. The parameters studied were total leukocyte and absolute cell counts, viability measured by dye exclusion, morphology, percentage phagocytic neutrophils, number of Candida organisms ingested per phagocytic neutrophil, candidacidal activity by differential staining, and chemotaxis under agarose. There was a progressive loss of neutrophils on storage that was statistically significant by 48 hr. Phagocytosis was the best preserved function. Microbial killing measured by candidacidal activity was less well preserved. Chemotaxis was the most poorly maintained parameter. There was mild impairment at 24 hr and a severe functional loss at 48 hr. The data suggest the following: (1) the first functions lost on storage are the most highly integrated, i.e., chemotaxis, followed by microbial killing and then phagocytosis; and (2) assuming that these functional losses are irreversible, storage of normal neutrophils used for transfusion should be limited to approximately 24 hr because a severe defect in migration occurs between the first and second days.


Erythropoiesis during recovery from iron deficiency: normocytes and macrocytes. In 26 patients with severe iron deficiency and microcytic anemia (MCV less than 70 fl), serial red cell size distribution histograms (erythrograms) were taken before and during iron therapy. Initially all patients had a single population of red cells, all microcytes. With the first reticulocytosis after iron therapy, a new population of cells appeared, larger in volume than the original. In 23 of 26 patients the new population of cells was of normal size (82-96 fl). In 3 of 26, the new population was macrocytic (MCV greater than 98 fl). Of these 3, 1 had folate deficiency; after folate was given, normocytes were produced. The other 2, both taking phenytoin and 1 a heavy alcohol using, had persistent macrocytosis despite folate administration. Erythrograms allowed quantitative, rapid evaluation of erythropoietic response to iron repletion. Abnormal macrocytic responses could be identified and seemed to occur with some frequency.


Erythropoiesis during recovery from macrocytic anemia: macrocytes, normocytes, and microcytes. In seven patients with marked megaloblastic anemia (MCV greater than 110 fl), red cell size distribution curves (erythrograms) demonstrated the size of red cells produced after therapy. In six, the new red cells were normocytic throughout recovery. In the seventh patient, folate repletion along produced a new population of microcytes, due to unsuspected iron deficiency; after iron repletion normocytes were produced. Three patients with autoimmune hemolytic anemia had macrocytosis (MCV greater than 110 fl) without folate or vitamin B12 deficiency. During recovery with predisone therapy, instead of a discrete new normocytic population appearing, the entire population progressively returned to normal size. Normal rather than "stress" reticulocytes, and remodeled stress reticulocytes remaining, may explain this different pattern of recovery. Two patients initially had minor subpopulations of smaller red cells that disappeared soon after therapy. These probably reflected the dyserythropoiesis of severe megaloblastic anemia.


The relation between baseline and 150 min platelet counts in response to selective beta-1-receptor blockade. An experimental study on healthy subjects. In 30 healthy volunteers after an oral administration of 50 mg metoprolol basal and 150 min platelet counts were determined. A significant negative correlation (p less than 0.01) between the baseline platelet count and the percentage increase at 150 min was shown to be present. It is postulated that this observation reflects interindividual differences between the magnitude of the exchangeable splenic platelet pool.


[Thrombophoresis I. Influence of centrifuge speed on thrombocyte yield, distribution of thrombocytes among centrifuge zones, and thrombocyte spreading (author's transl)]. Thrombocyte yields up to 1,4 X 10(11) per litre of separated whole blood were obtained using centrifuge speed up to 2000 RPM. With increasing speed, higher platelet concentrations in the thrombocyte zone were accompanied by a progressive decline of thrombocyte counts in the plasma zone, whereas the thrombocyte contamination in the erythrocyte zone remained unchanged. Taking into account both high extraction efficiency and good preservation of platelet function as measured by Breddin's spreading test, optimal conditions for thrombophoresis with the Aminco Celltrifuge have been obtained at 1600 RPM. Since repeated separation of the donor's blood resulted in a rising number of platelets with impaired spreading capacity, the total blood flow should be limited to the blood volume of the donor.


[Thrombophoresis II. Effects of thrombocyte separation on the blood donor (author's transl)]. The separation of approximately 75% of the platelets present in circulation and thrombocyte pool in healthy adult donors by continuous flow centrifugation lowers the mean thrombocyte concentration to 140 +/- 28 X 10(3)/microliter. A dangerous thrombocytopenia can not occur since the platelet count in the reinfused erythrocyte zone remains at around 88 X 10(3)/microliter. The reactive rise of the platelet count after separation, the extend of which depended on the total amount of harvested thrombocytes, reached values around 277 X 10(3)/microliter. The total thrombocyte yield exceeded the calculated yield by 30%, indicating emptying of a quiescent thrombocyte pool. Thrombopoietin activity could be demonstrated in donors' plasma at 12 and 24 hours after thrombophoresis.


The clinical efficacy of granulocyte transfusions: studies on the oral cavity. Patients with severe granulocytopenia of different origin received granulocyte transfusions. The migration and phagocytic ability of the transfused granulocytes in the oral cavity ("orogranulocytes") served as a parameter for measuring the viability of the granulocytes in vivo. There was no difference between granulocytes collected by continuous flow centrifugation and those collected by filtration leukapheresis. Under the influence of the transfusion treatment mucous membrane ulcers (MMU) subsided and healed. Where ulcers were present the number of orogranulocytes (OG) increased after granulocyte transfusion. In addition there was a significant correlation between the number of granulocytes in the peripheral blood and the number of orogranulocytes. As a control, orogranulocytes were studied in a group of healthy persons with intact teeth, toothless persons with normal blood counts and one patient with an acute agranulocytosis.


An improved modification of cycle filtration leucopheresis. We report about an own modification of repetitive cycle filtration leucopheresis (RFL). Compared to the method described by De Fliedner et al. (1974) it is simpler to perform, permits the use of commercially available filtration sets and thus reduces the costs of the procedure considerably. The mean yields of the granulocytes collected in 51 RFL from unconditioned normal donors amounted from 1.7 to 2.3 X 10(10) dependent on the number of the filtration cycles performed.


[Non-Hodgkin's malignant lymphoma. Retrospective study of 64 cases classified according to Kiel's and Rappaport's nomenclature]. 64 cases of non-Hodgkin malignant lymphomas were the object of a retrospective study: these 64 cases were considered in terms of Kiel's and Rappaport's classifications. The stimultaneous study using the two classifications showed that entities defined in one of them do not correspond to entities defined in the other one. --This study allows us to define: 1) in Kiel's classification, a groupe of lymphomas of favorable prognosis, by opposition with a group of lymphomas of poor progonosis, all stages included; 2) in Rappaport's classification, a group of nodular lymphomas of favorable prognosis, for which the actuarial survival curves, all stages included, seem to accord with the anatomico-clinical data thus far published. Nevertheless, while nodular lymphomas can be identified as lymphomas of favorable prognosis, it does not seem possible to isolate, in Rappaport's classification, a group of lymphomas of poor prognosis by opposition with the favorable prognosis group. This study confirms that, to the morphological entity of the malignant centroblastic centrocytic follicular lymphoma, there corresponds a lymphoma of favorable prognosis whose median is 72 months, all stages included, for an average age of 57.5 years (this median is more  than 180 months in the clinically localized stages). This morphological entity of Kiel covers 76 per cent of Rappaport's malignant nodular lymphomas. Nevertheless, 24 per cent of these same malignant nodular lymphomas are considered to be lymphomas of poor prognosis by Kiel and seem to appear as such in our study.


[Determination of the importance of environmental factors in human cancer: the role of epidemiology]. The evidence in support of the assertion that 80% of human cancers are of environmental origin is reviewed. The environment is used in its broadest sense and is taken to include the widespread general exposures of air and water pollution, the work environment, exposures resulting from personal choice such as smoking and drinking, and the diet. Several examples are chosen to show that a wide range of environmental agents can cause cancer. Consideration of descriptive epidemiological data relating to migrants, geographical variation in incidence, changes in risk over time, correlation studies, clusters and case reports, supports an environmental etiology for many cancers the cause of which is at present unkown. The same data can be used to show that a large proportion of cancer is likely to be due to environmental factors. If the lowest rate observed in a series of populations be regarded as representing a residuum of cancers due to non-environmental causes then it is possible to imagine a hypothetical population with a very low rate indeed. However, it is unlikely that such a level could be achieved even if all causal mechanisms were understood as it is possible that factors leading to one cancer may protect against another. Until evidence to the contrary is aduced it is held that the vast majority of human cancers are due to the environment: the reasons why there has been reluctance to accept this conclusion are discussed.


[Relations between biomedical variables: mathematical analysis or linear algebra?]. The authors, after a short reminder of one pattern's structure, stress on the possible double approach of relations uniting the variables of this pattern: use of fonctions, what is within the mathematical analysis sphere, use of linear algebra profiting by matricial calculation's development and automatiosation. They precise the respective interests on these methods, their bounds and the imperatives for utilization, according to the kind of variables, of data, and the objective for work, understanding phenomenons or helping towards decision.


[Use of models in the study of survival in oncology]. Observation of numerous survical surves connecting the survival rates with time usually expressed in yearly intervals has permited the elaboration of patterns describing survival probability in terms of time. Gross survival patterns, from which the most utilized is the exponential pattern, must be distinguished from comparative surival patterns that debouch into the recovery probleme. Their interest is to caracterize survival for a group of patients with the assistance of a limited number of values (three at most). From that, follow their practical applications: comparison between several groups that may differ either from the characteristics of the discase or from the received treatments and from the vital future forecasting, either on one group's level, or for an individual.


[Influence of the diagnosis of Hodgkin's disease on the quality of life of cured patients]. Authors present results of an inquiry dealing with familial and socio-professional reinsertion of 130 patients who have been treated for Hodgkin disease. On a family point of view, after treatment, the rate of single people is higher than in general population. Even though one can observe marriages, and feminine sterility is rare, the number of children by married couple remains low. There is no change in rate of house moving. Most of cured patients return to work. This fact is related to duration of treatment, but variations depend essentially of familial situation, kind to work and quality of previous social insurance. For two groups of people risk of unemployement is higher: agricultural labourers who are often dismissed and contractual civil servants who meet with difficulties to be established. Definitive invalidity is rarely conceded by wearied social organisms. Finally cured patients appear most of the time comparable with healthy population. However they meet with important difficulties to get a loan or to contract a life insurance. Premiums are frequently raised and policies restricted. Difficulties are not related to organic sequelae. Cured patients still remain suspicious for their entourage and employer, that bring them about to hide the pathologic episode.


[Cancer of the breast: Interrelations betwpen the primary tumor and the axillary and internal mammary nodes]. In a series of 300 patients operated for a cancer of the breast the internal and external mammary chain have been removed. The extemporaneous analysis has enable us to verify and complete the data collected at the clincial exmination. By this mean, we have selected on objective criteria the most favorables cases for conservative surgery. The histological examination of the lymph nodes shows a stricking relation between the T. and the N. This confirms the clinical conclusions. Finally we have shown that the appreciation of the T is of the outmost importance to predict an eventual envolvement of the internal mammary chain.


[Primary vaginal cancer in adults. Apropos of 72 cases treated at the Fondation Curie from 1956 to 1968]. Primary vaginal cancer are infrequent and amount to 2 or 3 per cent of the gynecological cancers. Their diagnosis is difficult, because many other cancers metastasize in the vagina. The primary vaginal cancer arise mostly after climateric. Adjuvant causes would be a total hysterectomy in the past, prolapsus, prolonged use a pessary or a previous irradiation. The squamous-cell carcinomas, by far the most frequent (91%), are mostly situated in the upper third of the vagina on the anterior and posterior walls. Surgery, being difficult and mutilating is rarely indicated. So the treatment is mainly radiotherapic: external irradiation and intracavitary curietherapy. The radiation techniques are a little different according to the site of the lesion in the lower third or not. The upper lesion can be treated like a cervix cancer. The lower ones  are more difficult to handle; for curietherapy, one must use molded apparatus, loaded with Iridium wire, adapted to each special case. The therapeutic results are rather poor:43 per cent for the 5-year cure rate and 36 per cent for the 10-year cure rate: less than for the cervix uteri. The upper lesions have a better prognosis than the lower ones. Results should be improved with an earlier diagnosis, a more accurate radiotherapy and a more precise dosimetry. The non-squamous-cell cancers (adenocarcinomas, sarcomas, mallignant melanomas) are generally rather radio-resistant. They are rare and their prognosis is very poor.


["In situ" anesthetics and experimental cryotumorectomy]. Some similarities have been found between the actions of anesthetics and freezing on biological membranes. Therefore, it has been thought that these agents could potentiate the destructive effect of cryosurgery. Experiments on cryopreservation of HeLa cells in vitro using three anesthetics--thiopental sodium, lignocaïne and CT 1341--indicate enhancement of "cryosensitivity". When using in vivo the same anesthetics injected in an experimental carcinoma (KDMC) of the Sprague-Dawley rat, cryosurgically treated, the results are: --no tumoricidal effect nor antitumoral activity of these agents when used alone,--the simultaneous use of anesthetics and cryosurgery gives better (but no significant results than cryosurgery alone,--the best agent in regard to this possible adjuvant effect seems to be thiopental sodium, it also facilitates tumoral dissemination. The authors conclude from these preliminary results that they need further experiments to assess this findings with smaller tumors, more numerous animals, same and others anesthetics at different concentrations. They attempt to define some caracteristics of potentiative agents during physical phase of cryodestruction.


Prolonged retention of methyl mercury by mallard drakes. Mallard drakes accumulated mercury rapidly from dietary dosage of methylmercury dicyandiamide and eliminated it slowly, retaining approximately one half at the end of 84 days; no measurable loss occurred between the end of the 7th and 56th days, but loss resumed concurrently with new feather growth, and continued through the 112th day, the close of the study.


Selenium in pollen gathered by bees foraging on fly ash-grown plants. Pollen collected from the rear legs of honey bees found foraging on asters voluntarily growing on a fly ash dump in Endwell, New York, was found to contain a high concentration of selenium. Pollen from bees foraging on asters growing on field soil contained no detectable selenium.


A search for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in an environment exposed annually to 2,4,5-trichlorophenoxyacetic acid ester (2,4,5-T) herbicides. As part of a broad study to determine whether 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD) is accumulating in the environment due to approved uses of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) based herbicides, samples of fish, water, mud and human milk were collected from areas in Arkansas and Texas where 2,4,5-T herbicides are used and were analyzed for TCDD. No TCDD was detected by a GC-MS procedure with a detection limit which averaged less than 10 ppt.


Self-assessment of hearing impairment: test of the expanded hearing ability scale questionnaire on hearing impaired adults in England. The National Center for Health Statistics developed a questionnaire for self-assessment of hearing impairment which has been widely tested in the United States. The performance of this questionnaire was tested on a sample of 131 people in England, known to have hearing impairment and gave results very similar to those obtained in the United States. These results are compared with a randomly selected sample from the general population. Characteristics of the hearing ability scale derived from the questionnaire are discussed and some suggestions made for a modified version of the questionnaire. The relationship between the average pure tone threshold and the score derived from the hearing ability scale questionnaire is described and takes the form of a bounded relationship with scale score indicating the minimum threshold level.


The speech spectrum--some aspects of its significance for hearing aid selection and evaluation. A spectral analysis of Australian speech is reported for 30 speakers, 15 males and 15 females. When expressed in one-third octave band levels, or critical band levels, the spectrum is essentially flat from 1kHz to 8KHz and shows approximately 15dB greater energy at 0.5kHz and lower frequencies. Although the results of this study agree substantially with other published data, the use of the average spectrum obtained, rather than the idealised speech spectrum, would be significant for aid selection and evaluation purposes. The common practice, in hearing aid literature, of showing the speech spectrum expressed in spectrum levels, rather than one-third octave band levels, may lead to a different, and possibly misleading, conceptualisation of the relative energy of high and low frequency components. Considering that speech spectra differ greatly from one individual to another, it would seem desirable that speech with a known, preferably average, spectrum be used in hearing aid evaluation procedures which involve setting the volume control of a hearing aid to deliver speech at a comfortable listening level.


Audiometric analysis as a predictor of speech intelligibility. This study examines the usefulness of the audiogram as a predictive instrument in speech intelligibility. Much of the early work on the audiogram centred on speech reception (e.g. Harris, Haines and Myers, 1956) but Montgomery (1967) made a case for the application to speech production especially when profoundly deaf children are involved. Speech intelligibility was measured by playing back to groups of listeners, tapes consisting of sentences read by 15-16-year-old schoolchildren. Listeners had to fill in two missing words in the sentences. Analyses of the pattern of hearing loss, of the loss at individual frequencies and finally, of combinations of the loss at different frequencies were made. The results indicate that in most circumstances, subjects may be placed in four distinguishable groups, separated at 65dB, and 105dB. When the simple mean of five frequency losses, centred on 1,000Hz is taken, five groups have significantly different levels of speech intelligibility.


Electrical stimulation of the human cochlea using a transtympanic electrode. Thirteen patients received stimulation of the cochlea using a transtympanic electrode. The purpose was to investigate the effect of alternating current on the normal and the damaged cochlea and also to discover what effect, if any, it has on tinnitus. Measurements were made of the electrical dynamic range and in one case a loudness balance test was performed against an acoustic signal in the contralateral ear. In addition nine patients experienced a variety of somatic sensations and four had vertigo. Tinnitus was temporarily suppressed in two out of nine cases.


Sex of listener and hormonal correlates of auditory thresholds. The present study investigates changes in auditory threshold during 4-6 week intervals for men, women on birth control pills, and normal cycling women not on birth control pills. Thresholds were determined at 250, 500, 1,000, 2,000, 4,000, 6,000, 8,000 Hz. Normal cycling females had significantly lower thresholds during first half of the menstrual cycle than during the second half. Females on birth control pills showed significantly and consistently lower thresholds than other listeners at several frequencies. Explanations for the phenomena are proposed.


Radio frequency clipping in hearing aids. For those patients with reduced dynamic range of hearing, accomodation of normal dynamic range of speech has always presented a problem. This paper describes a method of overcoming the problem, a method which has the added benefit of offering improved speech discrimination as well as limiting the output from a hearing aid system. The principle employed is the presentation of taped speech material processed through clipping of a radio frequency single side side band suppressed carrier signal, which is filtered to remove the Fourier components and demodulated to obtain the modified speech material. Groups of normally hearing and hearing impaired subjects undergo speech audiometry testing to assess what improvement can be effected by this system. The majority of subjects tested both normal and hearing impaired achieve improved speech discrimination when using the system described. Further once the output was set no increase in the input signal could produce a level in excess of that set by the output control.


Effects of jet aircraft noise on mental hospital admissions. We study, in the vicinity of Los Angeles International Airport, the effect of jet noise on mental hospital admissions. The maximum noise area (where the maximum fly-over noise exceeds 90 dBA) shows a 29% increase in admissions over those of a corresponding control area, as like the target area as possible, except that in the control area jet noise is not a dominant factor. The results are similar to those of a previous study carried out near Heathrow Airport.


Cardiac adrenoceptors at low temperature and the adrenoceptor interconversion hypothesis. 1 The hypothesis that low temperature converts inotropic beta-adrenoceptors to alpha-adrenoceptors has been tested in isolated heart preparations of the frog and rat. 2 The results do not support the adrenoceptor interconversion hypothesis. In the frog ventricle strip lowering the temperature from 24 degrees C to 14 degrees C did not significantly alter the inotropic potency of the sympathomimetic drugs isoprenaline, adrenaline and phenylephrine and did not reduce the potency of the beta-adrenoceptor blocking drug propranolol as an isoprenaline antagonist. In the isolated left atrium of the rat lowering the temperature from 31 degrees C and 24 degrees C to 17-19 degrees C did not significantly alter the inotropic potency of isoprenaline, noradrenaline and phenylephrine, did not diminish the potency of the beta-adrenoceptor blocking drug propranolol and did not increase the potency of the alpha-adrenoceptor blocking drug phentolamine. 3 Phenylephrine acted on alpha- and beta-adrenoceptors in rat left atrium at 31 degrees C and 24 degrees C, but only on beta-adrenoceptors at 17-19 degrees C.


Mechanism of nicotine-induced release of noradrenaline from adrenergic nerve endings. 1 A study of the mechanism of release of [(3)H]-noradrenaline ([(3)H]-NA) by nicotine from isolated vas deferens of the rat was made using incubation media of different ionic composition.2 Nicotine (20 mug/ml)-induced release of [(3)H]-NA was significantly potentiated in K(+)-free Krebs solution as compared to that in normal Krebs-Ringer solution.3 Nicotine-induced release of [(3)H]-NA was significantly reduced in Na(+)-deficient Krebs solution (containing only 11 mM Na(+)) and was abolished in Na(+)-free Krebs solution.4 In totally depolarized tissues, nicotine failed to cause an outflow of [(3)H]-NA but Ca(2+) (5 mM) did so.5 Nicotine required the presence of Ca(2+) in the incubation medium to cause release of [(3)H]-NA from adrenergic nerve terminals, the magnitude of release being dependent upon the concentration of Ca(2+).6 Nicotine-induced release of [(3)H]-NA was demonstrated in high Ca(2+), Na(+)-free Krebs solution in which all Na(+) had been replaced with Ca(2+).7 It is concluded that nicotine increases the membrane permeability to both Na(+) and Ca(2+). It is also suggested that the increase in permeability to Ca(2+) alone is not sufficient but a local depolarizing action of nicotine is necessary to cause release of noradrenaline from adrenergic nerve endings.


Ligand binding to muscarinic receptors in intact longitudinal muscle strips from guinea-pig intestine. 1 The binding of ligands to muscarinic receptors in intact longitudinal muscle strips from guinea-pig small intestine has been determined by measuring the inhibition of the irreversible binding of [3H]-propylbenzilylcholine mustard ([3H]-PrBCM). 2 The IC50 values for inhibition of [3H]-PrBCM binding by a given ligand were generally higher in intact strips than those reported for broken-cell preparations. This effect is probably due, at least in part, to the presence of an access-limitation factor in the kinetics of the irreversible binding of [3H]-PrBCM to the intact tissue. 3 The mean Hill coefficients for antagonist binding approached unity, but those for strong agonists were significantly less than unity. There was, with the possible exceptions of hexyltrimethylammonium and oxotremorine, reasonably good agreement with the Hill coefficients reported for brain homogenates.


The effects of intravenous anaesthetics on the cardiovascular system of the rabbit. 1 A pithed rabbit preparation is described that allows selective stimulation of the vertebral outflows. 2 The responses to stimulation of sympathetic vasopressor fibres were blocked by hexamethonium and phentolamine but potentiated by cocaine, whereas the responses to stimulation of cardioaccelerator fibres were blocked by propranolol. 3 Ketamine, althesin and pentobarbitone enhanced the effects of noradrenaline and attenuated the effects of sympathetic nerve stimulation. Thiopentone enhanced the effects of both noradrenaline and sympathetic nerve stimulation. 4 In pithed rabbits a transient, dose-related cardiovascular depression was produced by each agent irrespective of whether vasomotor tone was present whereas in decerebrate rabbits the corresponding cardiovascular depression was longer lasting. 5 It is concluded that the cardiovascular depression produced by intravenous anaesthetics in intact rabbits is due to a combination of central and peripheral effects.


Central and peripheral noradrenaline in the two kidney model of renovascular hypertension in the rat. 1 Plasma noradrenaline concentrations were similar in rats following unilateral renal arterial constriction (two kidney Goldblatt model) and in sham-operated control rats. 2 The development of hypertension was not affected by pretreatment with intracisternal injections of 6-hydroxydopamine. 3 These data suggest that sympathetic mechanisms do not contribute to the development of hypertension in this model.


Spasmogenic and potentiating actions of some amino acids on the guinea-pig myometrium. 1 Thirty-three amino acids were applied separately in concentrations of 2 to 10 mM to guinea-pig uterine horns in vitro at pH 7.4. About half the acids regularly produced contractions.2 Glycine and the straight-chain L-alpha-amino acids up to norleucine were active (longer ones not tested); D-isomers were less potent or inactive in these concentrations. The omega-amino acids gamma-aminobutyric acid (GABA) and delta-aminovaleric, and the alpha,omega-diamino acids L-alpha,beta-diaminopropionic and L-alpha,gamma-diaminobutyric were active, whereas others of similar chain-length such as beta-alanine and lysine were not. The diacidic acids, glutamic and homocysteic, were more active than the amido-amino acids, glutamine and asparagine. Histidine and phenylalanine showed little or no activity.3 The use of appropriate blocking agents indicated that the responses to representative acids were not mediated by histamine, 5-hydroxytryptamine, acetylcholine, noradrenaline or by prostaglandins. Attempts to block the actions of glycine and GABA with strychnine, thebaine, picrotoxin, bicuculline or tetramethylenedisulphotetramine (TETS) were unsuccessful.4 When some of the acids that were spasmogenic at 2 to 10 mM were applied at sub-spasmogenic doses, they transiently potentiated other spasmogens such as oxytocin or acetylcholine. This effect was also shown by a mixture of amino acids at approximately the normal plasma concentrations.5 There is some similarity between the spasmogenic activities of different amino acids and their known abilities to depolarize neurones.


Evaluation of the uptake of various amines into storage vesicles of intact human platelets. 1 The uptake of various 3H-labelled amines into a thrombin-releasable compartment of human platelets, thought to represent the platelet vesicular storage pool, has been evaluated. Measurable amounts of 5-hydroxytryptamine (5-HT), dopamine, tyramine, octopamine, and tryptamine accumulate in this pool, and also in a non-thrombin-releasable (cytoplasmic) pool during a 30 min incubation period with 10(-5) M extracellular amine concentrations. 2 No differences in the accumulation of vesicular or cytoplasmic 5-HT, dopamine, and tyramine are found in platelets treated with deprenyl to inhibit platelet monoamine oxidase as compared to controls. 3 Extracellular tyramine or dopamine in concentrations as high as 10(-5) M does not alter the initial rate of 5-HT uptake across the platelet plasma membrane. Similarly, sizable cytoplasmic pools of either amine do not alter the initial rate at which small amounts of 5-HT enter platelet cytoplasm or storage vesicles. 5-HT thus appears to be the preferred substrate for uptake into platelets and for movement from cytoplasm to vesicles.


The effects of pentobarbitone and chloralose anaesthesia on the vagal component of bronchoconstriction produced by histamine aerosol in the anaesthetized dog. 1 Total lung resistance (R(L)) and dynamic lung compliance (C(dyn)) were measured in dogs anaesthetized with pentobarbitone or chloralose and subjected to aerosols of histamine during 4 successive inspirations.2 Histamine caused concentration-dependent increases in R(L) and decreases in C(dyn). A significant vagal component was involved, but only when chloralose was employed and then only in the R(L) response.3 The resting values of R(L) and C(dyn) were similar regardless of which anaesthetic was used and remained essentially the same if the vagi were cooled.4 Electrical stimulation of the efferent vagi caused large increases in R(L) of dogs given chloralose and these effects were attenuated by the administration of pentobarbitone. Such stimulation was relatively ineffective in dogs given pentobarbitone alone.5In vitro, electrical field stimulation caused contractions of dog trachealis muscle. The responses were reduced by pentobarbitone in concentrations approximating to plasma levels in the anaesthetized dogs (1 to 5 x 10(-4) M), but the effects of exogenous acetylcholine were unaltered. The inhibition was dose-dependent, reversed by washing and unaltered by hexamethonium.6 The results suggest that pentobarbitone inhibits the vagal component of histamine-induced bronchoconstriction in the dog by an action on the efferent pathway. Furthermore, pentobarbitone acts either by blocking transmission along postganglionic parasympathetic nerves or by preventing the release of acetylcholine from the nerve endings in the lung.


Relaxation of isolated aorta of the rabbit by picolinic acids. 1 When the isolated thoracic aorta of the rabbit was contracted with prostaglandin F2alpha, 5-alkylpicolinic acids produced dose-dependent relaxations. 2 Picolinic acid, 2,5-pyridinedicarboxylic acid and 5-acetylpicolinic acid which do not have the 5-alkyl residue failed to relax blood vessels. 3 The vascular relaxation was dependent on the number of carbon atoms in the 5-alkyl compounds. 4 Relaxations which occurred with 5-alkylpicolinic acids were not affected by pretreatment with either propranolol or atropine. 5 It is concluded that the 5-alkyl residue is necessary for the vascular relaxation with 5-alkylpicolinic acid and that it was not produced by stimulation of beta-adrenoceptors or cholinoceptors but rather through an activation of the basic process.


The effect of atropine on acid secretion stimulated by acetylcholine, histamine and gastrin in the isolated whole stomach of the rat. 1 An isolated stomach preparation from immature rats has been used to study the effect of atropine on gastric acid secretion. 2 The acid secretory response to acetylcholine was not inhibited by atropine at a concentration of 0.3 micrometer. Concentrations of atropine of 1 to 3 micrometer produced a measurable inhibition of acid secretion, and a concentration of atropine of 10 micrometer caused a complete block of acid secretion which could not be surmounted by high concentrations of acetylcholine. 3 The acid secretory response to histamine was not inhibited by concentrations of atropine of up to 1 mM. 4 Concentrations of atropine of 1 micrometer and 10 micrometer did not inhibit gastrin-stimulated acid secretion, although a significant inhibition of acid output was observed with atropine at concentrations of 0.1 mM and 1 mM. 5 These findings are discussed in relation to the role of cholinergic mechanisms in the control of gastric acid secretion.


Effects of 3-methylindole in cattle.

Effects of 3-methylindole in cattle. 1 Rapid intravenous injection of 3-methylindole (3-MI) was shown to induce an anaphylactoid-like reaction in calves. 2 This was suggested by the reduction in response to a repeat dose of 3-MI, by the reduction of effects in the presence of antagonists to the putative mediators of anaphylaxis in cattle and by the production of signs similar to those seen in experimentally induced bovine anaphylaxis. 3 The plasma half-life of 3-MI was short (14.4 min) and, since absorption of 3-MI from the rumen is known to be slow, the extent of formation of 3-MI from L-tryptophan in the rumen would have to be substantial if 3-MI is to be considered the causative agent of 'fog fever', an acute respiratory distress syndrome seen in cattle.


Dopamine-induced depression of adrenergic nerve-mediated contraction of smooth muscle. 1 Dopamine (0.25-1.0 micrometer) applied extraluminally depressed vasoconstrictor responses of the perfused rabbit ear artery to low frequency adrenergic nerve stimulation. 2 The depressant effect of dopamine was prevented in the presence of haloperidol (0.1 micrometer) but not in the presence of phentolamine (0.03-0.14 micrometer). 3 Extraluminal dopamine (1 micrometer) or intraluminal injection of dopamine in amounts up to 0.025 micronmol had no dilator effect on arteries partially constricted by infusion of noradrenaline. 4 Dopamine also depressed contractile responses of guinea-pig vas deferens to low frequency adrenergic nerve stimulation. However, in this tissue the effect of dopamine was prevented by phentolamine but not affected by haloperidol. 5 In neither the rabbit ear artery nor the guinea-pig vas deferens did haloperidol increase the magnitude of responses to nerve stimulation or affect muscle sensitivity to noradrenaline. 6 We conclude that the adrenergic axons in the rabbit ear artery, but not the guinea-pig vas deferens, possess specific receptors for dopamine whose activation depresses axonal conduction or transmitter release. However, our results do not favour the view that these receptors are activated during normal transmission at physiological frequencies.


Electrocortical changes induced by the perfusion of noradrenaline, acetylcholine and their antagonists directly into the dorsal raphé nucleus of the cat. 1 The electrocortical changes induced by the perfusion of drugs directly into the dorsal raphé nucleus of the cat encéphale isolé preparation have been studied. 2 (-)-Noradrenaline (NA), (-)-adrenaline, or (-)-isoprenaline (Isop) produced intermittent or sustained electrocortical desynchronization during the perfusion period. 3 These changes were markedly attenuated or completely abolished by the prior perfusion of (+/-)-sotalol or (-)-propranolol, but not by equimolecular concentrations of (+)-propranolol. 4 The effects of NA or Isop were also blocked by phentolamine, whereas phenoxybenzamine either potentiated the responses to NA and Isop or mimicked the effects of these catecholamines. 5 The effect of dopamine was similar to that induced by NA, but could not be elicited at all of the perfusion sites where NA was effective. It could be blocked by (+/-)-sotalol or (-)-propranolol and also by the prior perfusion of fusaric acid. 6 Acetylcholine (ACh) increased, or initiated, electrocortical synchronization. These effects could be antagonized by sensory stimulation, the prior perfusion of atropine, or the simultaneous perfusion of NA at the same site. 7 Lignocaine, induced prolonged electrocortical desynchronization, behavioral alerting and an increased responsiveness to sensory stimulation. 8 The results have been discussed in relation to the possible involvement of inhibitory beta-adrenoceptors and facilitatory cholinoceptors (muscarinic) in the functioning of the dorsal raphé nucleus.


Effects of mianserin, a new antidepressant, on the in vitro and in vivo uptake of monoamines. 1 The effects of mianserin and of selected tricyclic antidepressants were compared in a number of monoamine uptake models. 2 The ability of mianserin to block the noradrenergic neurone membrane amine pump of rabbit brain stem slices was comparable to that of imipramine and amitriptyline and less than that of desipramine and nortriptyline. Both mianserin and desipramine were competitive inhibitors of noradrenaline uptake in vitro. The effect of mianserin on noradrenaline uptake in vivo was studied both peripherally and centrally. The ability of 6-hydroxydopamine to lower rat heart noradrenaline levels was found to be very sensitive to inhibition by tricyclic antidepressants. Mianserin was active in this model. However, its ability to block the 6-hydroxydopamine-induced fall in rat heart noradrenaline concentration was appreciably less than that of the tricyclics studied. 3 Mianserin, like tricyclic antidepressants, was essentially devoid of effect on dopamine uptake both in vitro and in vivo. 4 The ability of mianserin to inhibit [3H]-5-hydroxytryptamine uptake by rat hypothalamic synaptosomes was appreciably less than that of the tricyclic antidepressants studied. Mianserin was essentially devoid of effect on rat brain 5-hydroxytryptamine uptake in vivo. 5 It is concluded that in certain situations large doses of mianserin may block noradrenaline uptake in vivo. However, in no way does mianserin rival tricyclic antidepressants in blocking monoamine uptake in vivo. The clinical efficacy of mianserin cannot be attributed to inhibition of monoamine uptake.


The antidysrhythmic aminosteroid, ORG 6001, reduces the ST-segment elevation produced by coronary occlusion in the dog. ST-segment elevation following temporary coronary artery occlusion was measured from nine epicardial leads in open-chest anaesthetized dogs. This was greatly reduced by the prior administration of the anti-dysrhythmic aminosteroid, ORG 6001. It is suggested that this effect is related either to a reduction in the extent and degree of myocardial ischaemia or to prevention of K+ egress from ischaemic cells.


Reduced adrenal amine synthesis in spontaneously hypertensive rats after long-term treatment with propranolol. Male spontaneously hypertensive rats were either fed a diet containing 3 mg/g of (+/-)-propranolol, giving a mean daily intake of 178 +/- 4.2 mg/kg, or a control diet from 7 weeks of age for 6 months. Three days after cessation of propranolol-treatment, the arterial blood pressure of the treated group was about 10% lower than that of the control group. Adrenal dopamine content and tyrosine hydroxylase activity were reduced to 76% and 71% of the control values, respectively. The results indicate that propranolol causes a reduced sympathetic discharge through its central action, although blockade of beta-adrenoceptor-mediated local regulatory mechanisms cannot be excluded.