[Permeability of artificial lipid membranes to some enzymes]. The permeability of artificial lipid membranes for six enzymes, e.g. RNAse, trypsin, amylase, aldolase, invertase and alkaline phosphatase, was studied. The permeability coefficient values for these enzymes were calculated. It was shown that the penetration process consists of several steps: adsorption of enzyme on the membrane surface, diffusion of enzyme molecules through the lipid layer and enzyme desorption into the surrounding solution. The results obtained suggest that the diffusion of the enzyme molecules through the lipid layer is the limiting step of the penetration process.


[Determination of relative values of de novo biosynthesis and salvage pathway of thymidylate formation in rat decidual tissue]. A method for the determination of relative values (%) of two pathways of thymidine-5'-phosphate (dTMP) formation, e.g. via de novo biosynthesis and through thymidine reutilization (salvage pathway), is proposed. It is shown that the relative values of dTMP formation through the salvage pathway in the mesometrial part of developing decidua in pregnant rats (9-11th day of ppregnancy) are 1.5-3.4 times higher as compared to those in the antimesometrial part. When dTMP biosynthesis is suppressed by aminopterine, up to 80% of total DNA thymind is synthesized at the expense of thymidine reutilization. The incorporation of 3H-thymidine into DNA was thereby increased approximately 8-fold irrespective of the decrease in the DNA synthesis rate (approximately 2.4 times). The dependence of the relative values of the thymidine reutilization pathway on the correlation of the thymidylate synthetase and thymidine kinase activities in the tissue is discussed. The ability of the cells to reutilize thymidine is interpreted in terms of their relative resistance to the effect of folic acid antagonists.


[Organospecificity of chromatin fragmentation by endonuclease]. The analysis of chromatin fragments from liver, kidney, spleen and brain by means of electrophoresis in polyacrylamide gel concentration gradient has revealed the organospecificity of the chromatin fragmentation with endonucleases. The highest endonucleolysis of chromatin was observed in spleen nuclei, it was moderate in kidney and liver and it was practically absent in brain. Differences in endonucleolysis of the organs studied demonstrate their correlation with the mitotic activity.


[RNA-polymerase of murine leukemia L1210 cells]. Multiple forms of RNA polymerases (I, II and III) from murine leukemia L1210 cells are solubilized, purified and characterized. Heterogeneity of RNA polymerases I and III is revealed by chromatography on DEAE-Sephadex and Phosphocellulose (P-11). The properties of these forms such as peculiarities of transcription of native and denaturated DNA, metal ion dependence (Mg2+, Mn2+ and (NH4)2SO4) and alpha-amanitin sensitivity resemble those reported for other mammalian RNA polymerases. The level of RNA polymerase I of leukemia L1210 cells increase approximately ten-fold relative to its level in some organs of healthy mice.


[Comparison of free ribonucleotide pool in the spleens of C57BL and DBA/2 mice and in leukemia cells sensitive and resistant to 5-fluorouracil]. The amount of free purine and pyrimidine ribonucleotides in the spleens of mice (C57Bl and DBA/2) and in lympholeukemia cells (La and L1210), sensitive and with induced resistance to 5-fluorouracil, was determined by chromatography on a column with DEAE-cellulose. It was found that the cytidine ribonucleotide pool in the spleens of DBA/2 mice is 2 times lower as compared to C57Bl mice. The lympholeukemia cells (La and L1210) isolated from the animals also differed in their uridine nucleotide pools. The development of leukemia was accompanied by a decrease in ATP and GTP. No significant changes in the total amount of pyrimidine nucleotides under developing resistance to 5-fluororuacil were observed.


[Investigation of Ca2+ inhibitory effect on cellulase activity]. The Ca2+ effect on the activity of cellulase [beta-1-4-endoglucanase) is quantitatively estimated. Values of partial inhibition of the enzyme activity at different Ca2+ concentrations within 2-10 mM are determined. The type of inhibition is identified from the data on kinetic analysis. The values of substrate and inhibitory constants are calculated.


[Identification of albumin 0.19 in wheat and other cereal proteins]. It was found that albumin 0.19, being an inhibitor of alpha-amylases from human and insect saliva, is not specific for T. aestivum and is also revealed immunochemically by means of antiserum in the proteins of T. durum. Using rocket immunoelectrophoresis, it was shown that the albumin component specific for T. aestivum is not identical to albumin 0.19. The levels of albumin 0.19 in the proteins of wheat, aegilops. secale, agropyron and barley grains were studied.


[Effect of phosphatidylserine in hemocoagulating action of factors V, VII and autoprothrombin C]. It was found that phosphatidylserine inhibits the activating effect of factors V, VII and autoprothrombin C on the thromboplastin time of plasma. This is in agreement with the previously observed phosphatidylserine ability to form an inactive complex with the substrate of thrombinogenesis, i.e. prothrombin. The excess of autoprothrombin C results in changes in the kinetic parameters of the inhibiting effect of phosphatidylserine on the thrombinogenesis, which is indicative of the interaction between autoprothrombin C and phosphatidylserine. Data from gel-filtration on Sephadex G-100 and differential spectrophotometry support the evidence for the formation of the autoprothrombin C-phosphatidylserine complex. During ion-exchange chromatography and gel-filtration the autoprothrombin C preparations are eluted as an acute symmetrical peak; using electrophoresis in agarose gel, two fractions were revealed in the preparations. The first fraction migrates with gamma-globulins, whereas the second one--with alpha-globulins. The presence of phosphatidylserine in the autoprothrombin C solution does not change its migration rate during electrophoresis.


[Effect of Triton X-100 on properties of acetylcholinesterase from human erythrocytes]. The effect of Triton X-100 on catalytic properties of acetylcholinesterase from human erythrocytes under acetylcholine hydrolysis, on sensitivity of acetylcholinesterase to specific phosphoorganic inhibitors and eserine, and on the mobility and isoenyme spectrum under analytical electrophoresis in polyacrylamide gel is investigated. Triton X-100, independently on its concentration within 0.05-1.0%, slightly changes V and [S]opt values and increases Km value in 2-3 times. The inhibitory effect of Triton X-100 is mainly competitive, 0.5% Triton X-100 decreases bimolecular constant (kII) of the interaction of acetylcholinesterase with phosphoorganic inhibitor and eserine in 2.5-4 times. In the presence of phosphoorganic inhibitor, kII sharply decreased when 0.02% Triton X-100 was added, and then it did not change under the increase of Triton X-100 concentration up to 1.0%. On the basis of these data, an analytical method of estimating Triton X-100 content in protein solution is proposed. The introduction of 0.1% Triton X-100 into polyacrylamide gel results in considerable quantitative redistribution of acetylcholinesterase isoenzyme fractions and in the change of the mobility of one fraction under electrophoresis.


A family study of unsocialized aggressive boys. The psychiatric histories of relatives of 17 boys admitted to an inpatient unit with "unsocialized aggressive" behavior and of 19 boys admitted with other problems were investigated by means of structured interviews. The interviews were rated blind and diagnoses made on the respondents and relatives described in the family histories using research criteria. Fathers and combined parents of the probands qualified for the diagnosis of antisocial personality disorder more often than the fathers and combined parents of control boys. Uncles of probands and combined uncles and aunts more often had a history of marked antisocial behavior than the corresponding relatives of controls. Siblings of the probands more often had a history of behavior problems as children or adolescents than the siblings of controls. The data suggest an association between unsocialized aggressive reaction in boys and antisocial personality disorder in their adult relatives. Such an association is an interesting contrast to the relationship between hyperactivity in children and alcoholism in their adult relatives.


EEG frequency patterns associated with hallucinations in schizophrenia and "creativity" in normals. This study attempts to define EEG power spectral patterns associated with hallucinatory behaviors in schizophrenia. Six unmedicated schizophrenics with Schneiderian criteria were interviewed and their tongue potentials were monitored and recorded on FM tape. Eye movements and tongue potentials were monitored and segments with artifacts were not used. Consecutive 4-sec intervals of EEG were analyzed in the frequency domain using fast Fourier transorm methods and serial power spectra plots obtained. The intrusiveness of the hallucinatory experience may be similar to the sudden internal experience of perceptual resolution in a creative task. Six normal controls were similarly monitored and analyzed while responding to tests of "creativity." In the 4-sec interval prior to reports of hallucinatory experiences, a frequency pattern of predominatly delta and theta power was found in 71.7% of the EEG segments. In the control group, 78.1% of the EEG segments preceding a creative response demonstrated a similar low frequency pattern which also differed significantly from the base line EEG frequency pattern.


Evidence for the presence of m-tyramine, p-tyramine, tryptamine, and phenylethylamine in the rat brain and several areas of the human brain. Postmortem human brains have been obtained from four nonpsychiatric patients, aged 59-70 years. Regional analysis of the trace amines phenylethylamine, p-tyramine, m-tyramine, and tryptamine has indicated that the amines are distributed heterogeneously throughout the brain, but are most concentrated in the basal ganglia. Although the levels are very low, evidence obtained from animal studies has indicated that the trace amines have a very rapid turnover rate. Their presence in a brain synaptosomal fraction suggests a possible involvement in the process of neurotransmission. Postmortem changes in human brain amines are discussed in relation to those occurring postmortem in the rat brain, in which phenylethylamine, p-tyramine, and tryptamine have been shown to increase to levels greater than those prevailing in vivo.


Event-related brain potentials and selective attention to acoustic and phonetic cues. N1 and P3 components of the human event-related potential were recorded from subjects performing a syllable discrimination task which required selective attention to one ear at a time. The N1 component was enhanced to all stimuli in the attended ear; while the P3 component was enhanced only to the "target" stimulus in that ear. The results are discussed in terms of hierarchical stages of selective attention.


An experimental study of visual averaged evoked responses (V. AER) and pain measures (PM) in patients with depressive disorders. In a group of 100 patients admitted to the Department of Psychiatry in Umeå between January 1973 and July 1974 with depressive syndromes, pain measures - PM - and visual averaged evoked responses - V.AER - have been investigated and the patients have been rated by the doctor by means of the Cronholm-Ottosson depression rating scale. According to the results of V. AER patients have been grouped as augmenters or reducers, depending upon the tendency to augment or to reduce the intensity of incoming signals with increasing stimulus  intensity. V. AER are found to vary with age but not with sex. Differences are found between patients with and those without a psychotic dimension of their depressive syndromes. Patients with depressive syndromes of psychotic dimension tend more often to be reducers. When patients are divided according to diagnostic groups no differences are found. PM are found to vary with sex and detection threshold - DT - are found to vary with age while pain threshold - PT - tolerance level - TL - and pain endurance - PE - do not vary with age. Patients with depressive syndromes of a psychotic dimension are found to have higher PM while there is no consistent picture when patients are divided according to diagnostic groups. Possible explanations for contradictory results found by other authors are discussed.


The timing of CNV resolution in a memory retrieval task. Twelve men performed the Sternberg memory retrieval task while the EEG and EOG were recorded. Subjects saw a target set of 1 to 4 digits followed by a warning tone that was followed after 1.5 sec by a probe digit. Subjects indicated by pressing one of two levers whether the probe digit was in or out of the target set. The timing of contingent negative variation (CNV) resolution was measured as the latency of 50% resolution in stimulus-synchronized waveforms (SSWs), response-synchronized waveforms (RSWs), and model waveforms (MWs). The MWs were constructed by adding each RSW to itself using time displacements derived from the reaction times of the single trials of which the RSW was an average. The results indicated that CNV resolution is related to the timing of the motor response. MWs had resolution latencies close to those of the SSWs. In SSWs the N1 and P3 to the warning tone also varied with target set size.


Psychophysiological reactions to noise as modified by personal control over noise intensity. Effects of personal control over noise intensity were studied in experimental situations where subjects performed mental arithmetic under noise exposure. Every other subject was offered a choice between noise intensities, and the next subject, serving as his yoked partner, had to submit to the same noise. Mean measures of catecholamine and cortisol excretion, and of heart rate and subjective effort and discomfort showed that subjects were more aroused in the yoked situation. There were, however, considerable interindividual differences, subjects classified as 'internals' or 'externals' on the basis of the Internal-External Locus of Control Scale responding to the two experimental conditions in congruence with their general beliefs and attitudes with regard to control.


Interaction between physiological and cognitive determinants of emotions: experimental studies on Schachter's theory of emotions. This study investigated the interaction between physiological arousal and situation-derived cognitions in the determination of feeling states that is proposed in Schachter's theory of emotions. The degree of bodily arousal was varied by disguised oral administration of a placebo or the sympathicomimetic agent ephedrine. The situational circumstances were varied by instructions offering cues for (a) no emotions ('neutral' control), or the feeling states called (b) 'anger', (c) 'happiness', and (d) anxiety'. The subjects were 72 male students. The dependent variables were blood pressure, heart rate, a list of bodily symptoms, and an adjective check list. The results within the 'anger' and 'happiness' condition were in accordance with Schachter's theory: depending on the type of situation, ephedrine-induced arousal either decreased or increased positive descriptions of mood. The emotional effects of the 'anxiety' condition, however, were independent of the drug-induced arousal level. Contrary to Schachter's theory, anxiety reactions occured also in a state of low physiological arousal and did not increase with increasing arousal.


Temporal stability of solitary impulse solutions of a nerve equation. We study a differential equation that models nerve impulse transmission. The nonlinearity is simplified to be piecewise linear in order to allow explicit solution. In general, two solitary impulse solutions are exhibited. The temporal stability of these solutions is analyzed by a technique that identifies the number of unstable modes. These results extend the results of Rinzel and Keller (1973, Biophys. J. 13:1313) by showing that the slower unstable solution has only one unstable mode, and that the fast solution, as conjectured, has no unstable modes and is therefore stable.


The electrical response to light of bacteriorhodopsin in planar membranes. We have measured the light-induced short-circuit current generated by a planar membrane containing bacteriorhodopsin incorporated by vesicle fusion. The experimental results are consistent with an equivalent electrical circuit analogue that assumes that the vesicles remain intact after fusion and that the current generator equivalent of the light-driven proton pump is linearly dependent on bias voltage. The transient response to light of the planar membrane has also been examined. Slow response times are seen to be associated with the capacitive charging and discharging of the fused vesicles. A study of the leading edge of the light response curve of the planar membrane yields information about the transient response of the light-driven proton pump. We propose that the translocation of protons across the membrane is associated with a first-order process characterized by a rate constant lambda.


Experimental evidence for the role of cross-relaxation in proton nuclear magnetic resonance spin lattice relaxation time measurements in proteins. Proton nuclear magnetic resonance (NMR) spin lattice relaxation time (T1) and spin-spin relaxation time (T2) measurements are presented for a number of proteins with molecular weights spanning the range of 6,500-150,000 daltons. These measurements provide experimental evidence for the role of cross-relaxation in 1H NMR T1 measurements in proteins. The relationship between these measurements and the theory recently presented by Kalk and Berendsen is discussed. The results indicate that cross-relaxation dominates the T1 measurements for the larger proteins, even at relatively low resonance frequencies such as 100 MHz.


Simulations of conduction in uniform myelinated fibers. Relative sensitivity to changes in nodal and internodal parameters. Conduction of impulses in myelinated axons has been studied by a new method of computer simulation. The contributions of nodal and internodal characteristics and parameters were examined. Surprisingly, the conduction velocity, theta, was found to be quite insensitive to the nodal area or the exact description of its excitable processes. The conduction velocity also is relatively insensitive to the internodal length but much more sensitive to the myelin capacitance and axoplasm conductance. Qualitative change in theta with temperature depended on which temperature-sensitive parameters were included in the simulation.


Interpretation of biomembrane structure by Raman difference spectroscopy. Nature of the endothermic transitions in phosphatidylcholines. Raman difference spectroscopy has been applied to aqueous dispersions of dipalmitoyl phosphatidylcholine (DPPC). Difference spectra have been created by computer subtraction of absolute Raman spectra taken in each of three different temperature ranges: below the endothermic pretransition at 34 +/- 2 degrees C; between this temperature and the melting transition at 42 degrees C; and above the melting temperature. The resultant difference spectra are both quantitatively and qualitatively different, indicating that a distinct phospholipid conformation occurs in each of the three temperature ranges. Furthermore, the difference spectra show details of Raman spectral changes with greater clarity than is possible with conventional Raman techniques. A description of the lateral interchain order and the longitudinal chain order is given for each of the three temperature ranges. In addition to obtaining a more precise quantitative measurement of the changes in the Raman spectra, we observed some significant and previously unreported changes. It is suggested that distortion in the hexagonal lattice below the pretransition temperature previously reported by X-ray diffraction techniques may be responsible for interchain interactions which give rise to a Raman band observed only in the triclinic lattice of even-numbered n-alkanes.


Low-intensity two-step absorption of chlorophyll A in vivo. The intensity-dependent transmission of primary leaves of Triticum aestivum seedlings at lambda = 694 nm was measured with single pulses of a Q-switch ruby laser. At photon flux densities above 2 x 10(17) cm-2s-1 a decrease of transmission was observed. The result is interpreted as a two-step absorption of cooperative units of 10(5)-10(6) chlorophyll molecules.


Molecular weight of T2 NaDNA from viscoelasticity. The viscoelastic properties of T2 DNA solutions are used to determine the NaDNA molecular weight in four independent ways from the theory of the beads-springs model. The four molecular weights are 131.9, 132.7, 130.5, and 127.6 X 10(6). The average of these values, adjusted for the probable errors in viscoelasticity and concentration measurements, is (126 +/- 5) X 10(6). The four molecular weights are termed Mtaugamma11, Mtaueta, Mtaugamma, and MtauA; each is different in its sensitivity to molecular weight distribution. Their agreement suggests (1) that the theoretical equations relating each M to the corresponding measured properties are valid, (2) that T2 DNA behaves as a partially free-draining polymer chain, and (3) that our solutions were nearly homogeneous in DNA size. We show that serious errors can result if the viscoelastic properties are not extrapolated to their limits at zero shear rate, as well as at zero DNA concentration, before calculating molecular weight.


Potential and structure controlled interfacial behavior of uracil derivatives. The adsorption and related interfacial behavior of uracil, various methylated uracil derivatives, uridine, uridine-5'-monophosphate and uridine-3'5'-cyclic monophosphate has been studied by surface electrochemical measurements at a mercury electrode. All uracil derivatives exhibit an initial "dilute" adsorption region where the virtually flat uracil residue is absorbed flat on the electrode surface. In the case of uracil and its methylated derivatives the area occupied by one molecule is about 60-70 A2. Uracil, thymine and 1,5-dimethyluracil exhibit a second adsorption region where they rearrange on the surface and adopt a perpendicular orientation and occupy about 40 A2 per molecule. In this perpendicular orientation the uracils are bound to the electrode through the N(3)-H or perhaps N(1)-H functions in a manner similar to their Watson-Crick bonding in nucleic acids. When in the perpendicular orientation the adsorbed molecules undergo extensive stacking (association) interactions, again similar to those observed between adjacent bases in nucleic acids. The ability of a uracil derivative to undergo a surface reorientation is critically dependent on electrode potential, bulk-solution concentration and molecular structure.


Intrinsic and extrinsic fluorescence of histones H2A and H2B: a conformational study. Intrinsic and extrinsic fluorescence measurements suggest that H2A and H2B histones, in a partially secondary structure, self-aggregate into assemblies in which some tyrosine groups are buried in a hydrophobic environment and show enhanced fluorescence, 2-p-toluidinylnaphthalene-6-sulfonate (TNS) indicates heterogeneity among the binding sites whose number depends on the pH values of the solutions. Warfarin, used as hydrophobic probe, shows that during the process of self-association and cross-complexing of the two histones there is the covering of some hydrophobic sites of the proteins.


Thermal membrane potential across charged membranes in 2-1 and 1-2 electrolyte solutions. Measurements of thermal membrane potential across cation exchange membranes in MgCl2, CaCl2 and BaCl2 solutions and across anion exchange membranes in K2SO4, Na2SO4 and K2CO3 solutions were carried out. The magnitude of the thermal membrane potential for divalent counterions is lower than that for monovalent counterions. If the transport number of counterions in the membrane phase is unity, the slopes of the temperature coefficient of thermal membrane potential against logarithmic activities of counterion in the external solution are predicted to be--R/2F for 2-1 electrolytes with cation exchange membranes and R/2F for 1-2 electrolytes with anion exchange membranes, respectively.


Stopped-flow studies on the n equilibrium f transition in serum albumin. Stopped-flow studies of the refolding of iodoacetamide-blocked bovine serum albumin from the acid unfolded "F" state have been performed. If the protein is incubated with low concentrations of perchlorate anion then the refolding kinetics follow a simple first-order process. The dependence on pH of both the amplitude of the observed transients and the measured rate constants indicates that the N equilibrium F transition is highly cooperative. The results are consistent with the postulated multidomain structure of albumin which has been developed as a result of both sequence work and a variety of physical studies.


Pulse fluorimetry study in polarized light of DNA-ethidium bromide complexes. In previous works, a quantitative analysis of the fluorescence anisotropy decay, based on a comparison of the experimental measurements with a Monte Carlo simulation of the excitation energy migration, has been shown to provide the value of the unwinding angle of the DNA helix, induced by an ethidium bromide (E.B.) molecule intercalation. In the present work some of the characteristics of the model used in the computation are reexamined: namely the influence of the direction of the E.B. electronic moment, and the influence of the dye distribution along the DNA helix are studied. The computations are compared with experimental results obtained with new experiments performed with calf thymus and micrococcus lysodeikticus DNA-E.B. complexes. It is found that the difference in base composition of these DNA does not influence the fluorescence properties of their E.B. complexes. Our study confirms the validity of the dye distribution obtained with the single adjacent excluded site principle. Reasonable values of the unwinding angle are obtained by assuming that the transition moment direction lies along the great axis of the E.B. molecule. The value of this unwinding angle is compared with other values proposed in the literature.


Pyridine interactions with phenolic groups in water: evidence for hydrogen bonding and hydrophobic association. Pyridine interactions with phenol, substituted phenol, tyrosine and poly(Glu50,Tyr50) in aqueous solutions have been studied by ultraviolet (UV) difference spectroscopy, spectrophotometric pH titration, circular dichroism (CD) and proton magnetic resonance (PMR) spectroscopy. A red shift and spectral sharpening of the near-UV spectrum of phenol in water was noted at pyridine concentrations greater than 0.25 M. In addition, the spectrophotometric equivalence point for the phenol- or substituted phenol-phenolate equilibrium was increased about 0.5 pH units upon the addition of 1.0 M pyridine. PMR studies were consistent with the formation of a 1 : 1 phenol-pyridine hydrogen bonded complex. The equilibrium constant derived for this interaction, 0.6-0.7 M-1, is greater than the corresponding value for phenol-acetate hydrogen bonding in water. Enhancement of thepyridine hydrogen bond interaction with Tyr within poly(Glu50,Tyr50) was observed at pH greater than 12 due to a hydrophobic microenvironment produced by pyridine molecules intercalating between neighboring tyrosyl residues.


Physical properties of poly (3,N4-ethenocytidylic acid). Homopolymers of etheno CMP have been prepared by the action of polyribonucleotide phosphorylase upon etheno CDP. At alkaline pH the optical properties are consistent with a structure consisting of partially helical single-stranded chains whose helical regions are stabilized by base stacking. At acid pH the degree of helicity increases markedly. The degree of cooperativity displayed by the helix leads to coil transition induced by pH or temperature is less than for the case of polyribocytidylic acid. In the presence of acridine orange the alkaline form develops a strong extrinsic CD spectrum.


Scanning molecular sieve chromatography of interacting protein systems. Simulation of large zone behavior for self-associating solutes undergoing rapid chemical equilibration under kinetic control. Theoretical large zone reaction boundaries for molecular sieve chromatography have been simulated by computer for a self-associating solute undergoing rapid chemical equilibration under kinetic control. These patterns show that the kinetically-controlled reaction rate between the mobile and stationary phases is the principal determinant of the elution boundary profile in molecular sieve chromatography. The overall chemical reaction rate in the mobile phase was found to have a much greater role in a rapidly equilibrating system than did the effect of axial dispersion within the gel matrix.


Isoelectric focusing of a dimerizing solute in rapid chemical equilibrium: comparison of simulation procedures. The approach to isoelectric focusing equilibrium of a rapidly dimerizing solute was simulated by two different computing procedures: a stationary-grid model developed by Cann and Stimpson and a distorted-grid technique derived from the method of Cox. The results given by the two models were virtually identical at all times during the approach to equilibrium. Of the two procedures, the distorted-grid method has an advantage in computing time, while the stationary-grid model is applicable to a broader range of transport experiments. The effect on the focusing experiment of varying the electric field was examined by distorted-grid simulations. When the field was increased, the equilibrium distribution sharpened somewhat and the peak of the concentration profile shifted toward the isoelectric position of the dimer. The rate of approach to equilibrium was approximately proportional to the field strength.


Thermodynamics of the glutamate dehydrogenase catalytic reaction. The enthalpy change for the oxidative deamination of glutamate by NADP+ catalyzed by bovine liver glutamate dehydrogenase has been determined calorimetrically. The deltaH0 values are 64.6 +/- 1.2 kJ/mol and 70.3 +/- 1.2 kJ/mol at 25 and 35 degrees C respectively. The equilibrium constants for the reaction at the two temperatures were determined spectrophotometrically. This enabled the determination of deltaG0 and deltaS0 of the reaction as well. deltaH0 values were also determined for the reaction using an alternative coenzyme and the deuterated substrate.


The equivalent conductivity of aqueous solutions of alkali metal salts of a number of ionic polysaccharides. Measurements of the equivalent conductivity of aqueous solutions of alkalimetal salts of a number of ionic polysaccharides at 25 degrees C are reported. The polysaccharides studied are: (1) three carboxymethylcelluloses of various degrees of substitution (Li+, Na+, Cs+ salts) in the concentration range 4 X 10(-4) - 6 X 10(-2) equivalents alkali ion per liter, (2) Polypectate (Li+, Na+, K+, Cs+ salts) in the range 1.5 X 10(-4) - 2 X 10(-2) equivalent alkali ion per liter, and (3) Dextransulfate (Li+, Na+, K+ salts) in the range 3 X 10(-4) - 10(-1) equivalent alkali ion per liter. The results are compared to some earlier data and to a limiting law for conductance of rod-like polyions derived by Manning. It is concluded that although qualitative agreement is obtained between observed data and the limiting law when various polyions of different charge densities are compared at a given concentration, the concentration dependence predicted by the limiting law is in agreement with the observed curves only for polyions of a relatively low charge density. At higher charge densities appreciable deviations occur, and dextransulfate which does not have the rod-like polyion structure required by theory does not conform to the predicted concentration dependence at all.


Polypeptide sequencing by liquid chromatography mass spectrometry. Key steps in a proposed automated system for polypeptide sequencing utilizing a liquid chromatograph mass spectrometer computer system have been tested with mixtures containing up to six model oligopeptides. At the low nanomole level it was possible to obtain complete sequence information for all components in many, but not all, of the mixtures tried. Interpretation of the results is complicated by the presence of numerous side-products formed in the derivatization process. Minimization of such impurities will be necessary to reduce the ambiguity of the sequence information resulting from more complex mixtures, such as those expected from the degradation of larger polypeptides, and to reduce sample requirements to the subnanomole level. However, the present system appears to have unique advantages over other proposed automated methods.


The formation of cyclized silyl derivatives of beta-hydroxyamines and their analyses by means of gas chromatography mass spectrometry. A generally applicable silylation method for beta-hydroxylated primary, secondary, tertiary and even quaternary amines is presented. These aminoalcohols form 6-membered heterocycles under the influence of a reagent mixture consisting of 1,3-bis-(chloromethyl)-1,1,3,3-tetramethyldisilazane and chloromethyldimethyl-chlorosilane. Examples of analogue ring closures with a gamma-hydroxyamine and an alpha-amino acid are also given. The formation of the derivatives and their properties, are discussed, mainly from the viewpoint mass spectrometry.


A simplified technique for collecting breath CO2 for isotope ratio mass spectrometry. A simplified technique of collecting breath CO2 for isotopic analysis has been developed. The subject breathes into a 3 1 bag from which a 50 ml aliquot is transferred to an evacuated, septum-capped tube (Vacutainer). The sample is later withdrawn and the CO2 is cryogenically purified. No isotope fractionation is observed in samples collected in this manner. Samples have been stored up to three months without any change in the isotope ratio.


Negative ion mass spectroscopy of natural products. VIII. alpha-Amino acids. The negative ion mass spectra (2-4 eV) of twenty free alpha-amino acids have been investigated and compared with the respective low voltage positive ion mass spectra (6-16 eV). The important fragmentation processes are discussed.


Electrohydrodynamic ionization mass spectrometry of biochemical materials. Electrohydrodynamic ionization mass spectrometry has been applied to a range of biochemical materials dissolved in glycerol with NaI as electrolyte. Sugars (glucose, sucrose, raffinose), nucleosides (adenosine, thymidine, uridine), a tripeptide (glutathione) and an aminocyclitol antibiotic (neomycin) have been analyzed. Unambiguous analysis of a multicomponent solution has been demonstrated. All samples yielded several quasimolecular ions involving either proton or cation attachment to clusters of sample and/or solvent molecules. Unlike other techniques such as field desorption, electrohydrodynamic ionization is not observed to cause fragmentation of sample molecules. The mass spectrometer was operated so as to analyze only those ion clusters which had not undergone decomposition processes; under these conditions, most materials are ionized with similar efficiencies if the total abundance of all characteristic quasimolecular ions is considered. Information regarding the amino acid sequence of glutathione was obtained by thermal pretreatment of the glycerol solution before mass analysis. Positive and negative ion spectra give complementary information which can resolve potential ambiguities regarding the exact composition of quasimolecular ions. Electrohydrodynamic ionization mass spectrometry should be applicable to materials which cannot be ionized by other methods.


The determination of 2,3,7,8-tetrachlorodibenzo-p-dioxin in biological extracts by gas chromatography mass spectrometry. Using both gas chromatography low resolution mass spectrometry and gas chromatography high resolution mass spectrometry, 2,3,7,8-tetrachlorodibenzo-p-dioxin at the part per trillion level may be determined in pre-concentrated extracts of bovine fat, liver and milk; human milk; rats; rice; grass; soil and water. Criteria are set forth for the objective determination of detection limit, signal and noise as applied to these determinations.


Gas chromatography chemical ionization mass spectrometric analysis of diminazene in plasma. A quantitative and sensitive method was developed  for the determination of diminazene in plasma. The assay involves the reduction of diminazene to 4-aminobenzamidine and 4-hydrazinobenzamidine. The latter is further reduced to give an additional mole of 4-aminobenzamidine which is extracted, acetylated and condensed with hexafluoroacetylacetone to form a volatile derivative that is subsequently analyzed by gas chromatography chemical ionization mass spectrometry. 4-Aminobenzylamidine was synthesized and used as an internal standard. The method is reproducible and its sensitivity limit using 1 ml of plasma is 0.1 microgram diminazene ml-1. This sensitivity limit is sufficient to detect plasma levels in cattle following therapeutic doses of the drug.


Gas chromatography mass spectrometry studies on biologically important 8-aminoquinoline derivatives. Several substituted 8-aminoquinolines related to known antimalarial drugs have been studied by gas chromatography mass spectrometry. 5,6-Dihydroxy-8-aminoquinoline, a possible metabolite of Primaquine, can be detected by single ion monitoring after conversion to a trimethylsilyl ether derivative. The mass spectra obtained in this study indicate that there are certain ions which are characteristic of the trimethylsilyl ethers of hydroxylated 8-aminoquinolines and 5,6-dimethoxy-8-aminoquinolines. These compounds should thus be amenable to analysis if they were produced during in vivo metabolism studies. Using selected ion monitoring the derivatized compounds can be detected at submicrogram levels.


Gas chromatographic mass spectrometric identification of N-dicarboxylmonoglycines. A number of N-dicarboxylmonoglycines of biological interest have been synthesized. They were characterized by means of mass spectrometry. Gas chromatography of the methyl esters of methylmalonyl-, succinyl-, glutaryl-, adipyl-, suberyl- and sebacylglycines showed a single sharp peak for each compound on Dexsil 300 and OV-17 columns. Methylene unit values and mass spectra of the six methyl esters are reported.


Electron impact mass spectra of 1-methyl-oestra-1,3,5(10)-trienes having intact and 13,17-seco-D-ring structures. Electron impact mass spectra of 1-methyl-oestra-1,3,5(10)-trien-17-one, its oxime, the homologous 18-norketone, 1-methyl-oestra-1,3,5(10),13(18)-tetraene-17-carbonitrile and the corresponding 13,17-seco epoxide are described. The major fragmentation pathways of these compounds are reported and discussed in relation to their structures, and the structures of the ions m/e 144, 157, 170 and 183 characteristic of the 1-methyl-oestratriene skeleton are described. The relative abundances of these characteristic ions were shown to relat to the presence or absence of a 13,17-seco-D-ring in these compounds.


Studies on trimethylsilyl derivatives of 1,2-dialkylglycerols by gas-liquid chromatography mass spectrometry. Trimethylsilyl derivatives of 1,2-dihexadecyl- and 1,2-dioctadecyl-glycerols were subjected to analysis by a gas chromatograph mass spectrometer system. The mass chromatographic identification of four kinds of glycerophospholipids, 1,2-dihexadecyl, 1-hexadec-1-enyl-2-hexadecanoyl, 1-hexadecyl-2-hexadecanoyl- and 1,2-dihexadecanoyl-glycerol is also described.


Origin of nitrogen in the biosynthesis of carbamoylpolyoxamic acid. The biosynthetic origin of the carbamoylpolyoxamic sidechain of the polyoxin nucleoside peptide antibiotics was studied using 15N labeled alpha-amino-S-hydroxyvaleric acid as precursor. Gas chromatography mass spectrometry of polyoxamic acid isolated from culture filtrates of Streptomyces cacaoi var. asoensis showed incorporation of the nitrogen atom of alpha-amino-S-hydroxyvaleric acid into carbamoylpolyoxamic acid with an isotopic dilution factor of 23, thus establishing the intermediacy of alpha-amino-S-hydroxyvaleric acid and determination of the full biosynthetic pathway.


Continuous dehydrogenation of a steroid with immobilized microbial cells: effect of an exogenous electron acceptor. Whole cells of Pseudomonas testosteroni, induced to synthesize steroid-transforming enzymes beforehand, have been immobilized by entrapment in polyacrylamide gel. The immobilized cells have been used to catalyze the continuous delta1-dehydrogenation of Reichstein's substance S under various conditions in the presence of phenazine methosulfate (PMS), an electron acceptor for the cell-free delta1-dehydrogenase. The presence of PMS substantially increases the rate of reaction when fed with the steroid substrate to a continuous stirred tank reactor containing the immobilized cells. The operational half-life of the delta1-dehydrogenase activity of the cells, about 103 hr under the best operating conditions, is essentially unaffected by the presence of PMS. Though the acceleration of the reaction may be due to PMS-mediated passage of electrons from some component in the electron transport chain to molecular oxygen, the lack of a similar effect with methylene blue is consistent with the conclusion that PMS functions directly as the electron acceptor for the delta1-dehydrogenase.


Determination of redox potential levels critical for cell respiration and suitable for L-leucine production. The effect of oxygen supply on L-leucine fermentation was investigated employing a leucine-producing mutant of Brevibacterium lactofermentum. Since it was not possible to measure oxygen tension below 0.01 atm by a Teflon-coated oxygen electrode, the degree of satisfaction of the cells' oxygen demand (cells' respiration rate/maximum oxygen demand of cells, rab/KrM) and the redox potential of the culture medium (E, mV) were used as indices to oxygen supply in cultures under low oxygen tension. When the oxygen demand of the cells was satisfied (rab/KrM = 1.0) and the E value was between --90 and --110mV, L-leucine formation was 26.5 mg/ml. When the oxygen demand of the cells was not satisfied (rab/KrM = 0.85) and the E value was between --200 and --220 mV, L-leucine accumulation was 29.7 mg/ml. When the oxygen supply was extremely limited (rab/KrM = 0.27) and the E value was --280 mV, L-leucine formation was 12.9 mg/ml. A new method which simultaneously measures the redox potential and dissolved oxygen was applied to the determination of the critical dissolved oxygen level for cell respiration (PL crit), whick was too small to be detected by conventional oxygen electrodes. The value of PL crit of the leucine producer was estimated as 0.0002 atm.


Metabolic dependence of protein arrangement in human erythrocyte membranes. I. Analysis of spectrin-rich complexes in ATP-depleted red cells. The discocyte-echinocyte transformation and the decrease in deformability associated with red cell ATP depletion have been attributed to changes in the physical properties of spectrin and actin, membrane proteins located at the membrane-cytosol interface. We investigated the spontaneous formation of spectrin-rich complexes in human erythrocyte membranes, employing two-dimensional SDS-polyacrylamide gel electrophoresis. Membranes of red cells depleted in ATP under aerobic conditions exhibited (1) an increase in components 4.5 and 8 and globin subunits, (2) a spontaneous formation of heterodimers of spectrin 1 + 2 and spectrin 2 + component 4.9, and (3) a large molecular weight (greater than 10(6) daltons) protein complex with a high spectrin to band 3 ratio. These complexes were dissociated with dithiothreitol and were prevented by anaerobic incubation or the maintenance of red cell ATP and GSH levels with glucose, adenine, and inosine. The complexes 1 + 2 and 2 + 4.9 were also seen in acetylphenylhydrazine-treated, glucose-6-phosphate dehydrogenase-deficient fresh erythrocytes that showed marked GSH depletion but preserved greater than 70% of the original ATP level. However, membranes of these cells did not contain the greater 10(6) dalton aggregate with a high spectrin to band 3 ratio. We concluded that the formation of the latter complex results from rearrangement of spectrin and other polypeptides in membranes of ATP-depleted red cells. Under aerobic conditions, the rearranged proteins undergo spontaneous intermolecular crosslinkings through disulfide couplings.


Determinants of fecal and urinary iron excretion in desferrioxamine-treated rats. Radioiron excretion in the urine and feces after continuous subcutaneous infusion of desferrioxamine (DF) was studied in normal and hypertransfused rats in whom reticuloendothelial and parenchymal iron stores had been labeled by selective 59Fe probes. The existence of two alternative pathways for the chelation of iron in vivo by DF was indicated by the results. The first pathway was intracellular chelation in hepatocytes with chelated iron excreted through the bile only. The second pathway, which was extracellular, could only be activated after saturation of the transferrin iron binding capacity, with the chelated iron excreted by the kidneys. The last mechanism was probably identical with the mode of action of diethylenetriaminepentaacetic acid (DTPA). Further studies will be required in order to establish whether the enhancement in iron chelation obtained by the continuous infusion of DF in patients with complete saturation of circulating transferrin may or may not be related to the extracellular mechanism of iron chelation in hypertransfused rats.


Lack of protective effect of autotransplanted splenic tissue to pneumococcal challenge. Studies in animals and clinical experience in patients have demonstrated that splenectomy may lead to an increased susceptibility to infection. The infections are usually caused by encapsulated bacteria such as penumococcus. It has been shown in a variety of experimental animals that autotransplanted splenic tissue is capable of regenerating into implants that are microscopically indistinguishable from normal spleen and of restoring a number of normal splenic functions. The response to intravenous challenge with Streptococcus pneumoniae, type 25, was therefore studied in control, asplenic, and autotransplanted Sprague-Dawley rats. Despite previous observations that a number of immune functions can be restored in this animal model by autotransplanted splenic tissue, the present study indicates that splenic tissue autotransplants do not restore the ability to resist intravenous pneumococcal challenge.


Endotoxin-induced changes in human platelet membranes: morphologic evidence. Interaction between human platelets and bacterial endotoxin was studied in vitro with transmission and scanning electron microscopy. Washed human platelets, whose aggregation was blocked with apyrase, were incubated in a plasma-free medium containing crude endotoxin that had previously been complexed with copper. Thirty minutes of incubation resulted in adherence of endotoxin particles to the platelet surface, breaks in the platelet plasma membrane with apparent attempts at repair, pseudoped formation, and centralization of platelet organelles. Copper appeared to potentiate these phenomena, since neither Cu2+ at low concentrations nor endotoxin alone altered the morphology of the platelet membrane. This platelet-endotoxin interaction may be an intermediary step in the detoxification and clearance of endotoxin from the plasma.


Concentration gradient of blood stem cells in mouse bone marrow--an open question. The distribution of pluripotential blood stem cells (CFU-S) in bone marrow was studied in four strains of mice. Analyses of paired samples containing various fractions of axial and marginal bone marrow cells, as well as longitudinal 200-micrometer sections, revealed a rather uniform spatial distribution of CFU-S across the diameter of the femoral medullary cavity, in contrast to the finding by others of a CFU-S concentration gradient extending from the endosteum to the central longitudinal axis of bone marrow. The existence of a stem cell gradient is therefore open to question.


Three stages of erythropoietic progenitor cell differentiation distinguished by a number of physical and biologic properties. Previous studies have shown that erythroid precursors at sequential stages of differentiation along the red cell pathway can be distinguished by differences in the size and maturation kinetics of the colonies to which they give rise in vitro. Using criteria based on these two parameters, it is thus possible to identify three distinct erythroid progenitor cell populations in the mouse, known as day 8 BFU-E, day 3 BFU-E, and CFU-E. These cell types have now been shown to differ in a number of other respects, including progenitor cell size, sensitivity to cycle-active agents, response to plethora, and effects of the W/Wv genotype. In addition, a comparison of the differences found between day 8 BFU-E and day 3 BFU-E on one hand and those distinguishing day 3 BFU-E and CFU-E on the other provides support for the view that early erythropoietic cell differentiation involves a series of changes that take place long before competence to synthesize hemoglobin becomes manifest.


Fetal erythropoiesis in steel mutant mice. III. Defect in differentiation from BFU-E to CFU-E during early development. Erythroid progenitor cells in +/+ and Sl/Sld fetal livers manifested as burst-forming units-erythroid (BFU-E) and colony-forming units-erythroid (CFU-E) were assayed in vitro during early development. The proportion of BFU-E was higher as mutant than in normal fetal livers. On the other hand, the proportion of CFU-E was less in the mutant than in the normal. These results suggest that the defect in Sl/Sld fetal hepatic erythropoiesis is expressed at the steps of differentiation that effect the transition from BFU-E to CFU-E.


Effect of protein deprivation on extrarenal erythropoietin production. The production of erythropoietin by rats fed a protein-deficient diet is markedly decreased. This defect can be rapidly reversed by feeding protein. In the reported experiments we investigated the effect of protein deficiency on the extra-renal production of erythropoietin. The results indicate that the production of erythropoietin in nephrectomized animals is insensitive to protein depletion.


Validity of the Wu-Hoak method for the quantitative determination of platelet aggregation in vivo. Quantitative determinations of platelet aggregation were made by a modified version of the Wu-Hoak-method in venous blood samples from ten healthy volunteers. It was demonstrated that the extent to which aggregates are formed depends on the rate of flow in the needle and on other methodical influences as well as on the platelet count. Accordingly, no definite conclusions concerning aggregation conditions in vivo can be drawn from the results obtained with venous blood samples.


Quantitative changes in platelet aggregation due to physiological and pathological factors and medication. Quantitative measurements of platelet aggregation in samples of venous blood were made in altogether 66 healthy volunteers by a modified version of the method of Wu and Hoak. The formation of aggregates was found to be unaffected or at the most barely affected by such factors as sex, age, smoking, fatty food, physical exertion and medication with isoprenaline or ovulation inhibitors. No difference in the number of aggregates formed was noted between 12 control patients and 16 patients with myocardial infarcts or 14 with other conditions predisposing to arterial thrombosis. Anticoagulant therapy had no effect on aggregation. It is suspected that aggregation in vitro due to methodological factors may obscure any quantitative alterations in the formation of aggregation present in vivo.


[The determination of the red cell isoenzymes 6-phosphogluconate dehydrogenase (E.C.1.1.1.44) and acid phosphatase (E.C.3.1.3.2) by means of agarosegel thinlayer electrophoresis (author's transl)]. Methods for the determination of the red cell isoenzymes 6-PGD and acP by means of agarosegel thinlayer electrophoresis are referred. Using these relatively simple techniques, results can be obtained after at least two hours. The quality of separation in both systems is higher than that obtained after starch gel electrophoresis.


[Quantitative analysis of fibrinmonomer in Arwin-therapy (author's transl)]. The quantitative measurement of plasma fibrin monomeres in three patients with Arwin-treatment by affinity chromatography on agarose fixed fibrinogen and the "tüpfel method" demonstrated high specifity and sensitivity. Plasmafibrinmonomer concentration clearly differs both before and during treatment from results reported in the literature. The method results in a better control of dangerous situation, especially with additional application of fibrinolytic agents.


Early experiences in organising and running a replantation service. In the 10 months since the establishment of a 24-hour replantation service, the centre at the Klinikum rechts der Isar of the Technical University of Munich has treated 162 amputation injuries; 132 underwent replantation surgery and 117 of these healed successfully. Surgical technique, medication and postoperative treatment with physiotherapy are described. Special emphasis is placed on the difficulties associated with crush and avulsion injuries; in most of them the only solution is an intermediate vein graft to bridge the defect in the vessels.


Inhibition of precursor incorporation into nucleic acids of mammalian tissues by antimalarial aminoquinolines. 1 Chloroquine, primaquine and ethidium inhibitied thymidine incorporation into deoxyribonucleic acid of rat tissues when administered concurrently with the labelled precursor. 2 Chloroquine and primaquine inhibited the incorporation of uridine and adenine, but not orotate, into various ribonucleic acid fractions of liver of rats and mice. These drugs had no effect on leucine incorporation into hepatic protein in rats or mice. 3 Although chloroquine and primaquine are active against different stages in the life cycle of the malarial parasites, the two aminoquinolines exert similar effects in rodent tissues.


The effects of amino acids and antagonists on the isolated hemisected spinal cord of the immature rat. 1 Records of ventral and dorsal root polarity of the isolated hemisected spinal cord of the 3-9 day old rat showed that respective dose-dependent depolarizations of motoneurones (VR responses) and primary afferent terminals (DR responses) were produced by both acidic and neutral amino acids in the presence of procaine (1 mM) or tetrodotoxin (0.1 micron). 2 Of the four neutral amino acids, gamma-aminobutyrate (GABA), glycine, taurine, and beta-alanine, GABA was the most effective in producing DR responses and glycine the most effective in producing VR responses. Only taurine depressed the electrical activity recorded from ventral roots. 3 The DR responses produced by GABA, beta-alanine and taurine were all antagonized by bicuculline (5 micron) and picrotoxin (5 micron). Bicuculline was more selective than picrotoxin in antagonizing VR responses produced by GABA.  4 Strychnine (1 micron) antagonized VR responses produced by glycine beta-alanine and taurine without affecting responses produced by GABA. DR responses to the neutral amino acids were unaffected by strychnine.


The metabolism of prostaglandins by the guinea-pig uterus with particular reference to corpus luteal maintenance in early pregnancy. 1 Homogenized lung tissue from day 15, pregnant and non-pregnant guinea-pig metabolized exogenous prostaglandin E2 (PGE2) and prostaglandin F2alpha (PGF2alpha) almost completely when incubated in Tyrode solution containing beta-nicotinamide adenine dinucleotide (NAD+). 2 Metabolism of PGE2 and PGF2alpha by homogenates of day 15, pregnant or non-pregnant, guinea-pig uteri was relatively low (8 to 20%) when incubated in Tyrode solution containing NAD+. 3 Day 15, guinea-pig conceptuses (placentae and embryos), homogenized and incubated in Tyrode solution containing NAD+, metabolized prostaglandins to a slightly greater extent (14 to 22%) than day 15, uterine tissue. 4 Addition of exogenous arachidonic acid to day 12 or day 15, pregnant, guinea-pig uterine homogenates in Tyrode solution did not increase the yield of PGF2alpha following incubation. 5 It is concluded that neither an increase in metabolism of PGF2alpha by the uterus and conceptus nor lack of precursor is responsible for the lower secretion of PGF2alpha from the day 15, pregnant, guinea-pig uterus when compared to the day 15, non-pregnant uterus.


Initial investigations into adrenaline accumulation and adrenergic responsiveness in cultured neonatal rat heart cells. 1 Accumulation of tritiated adrenaline (and/or its products) has been studied by a variety of techniques in viable, attached and free-floating myoblasts cultured from neonatal rat heart cells. 2 Accumulation increased with the number of cells used, the culture age of cells, incubation time and the concentration of adrenaline in the incubation mixture. 3 Accumulation-concentration data were not linearly correlated with dose-response data. 4 Accumulation did not correlate well with beta-adrenoceptor responsiveness in a number of situations of varying responsiveness. 5 Accumulation was not blocked by a variety of uptake blocking agents or alpha- and beta-adrenoceptor antagonists. 6 A much smaller accumulation process was observed in fibroblasts which respond to adrenaline with reversible morphological changes.


Effect of parathyroidectomy on cardiovascular reactivity in rats with mineralocorticoid-induced hypertension. Previous work has shown that parathyroidectomy protected Sprague-Dawley rats against mineralocorticoid hypertension. 2 In order to explain this protection, we studied vascular reactivity to noradrenaline and angiotensin II in several groups of rats with and without their parathyroid and thyroid glands. Work was performed in vagotomized, anaesthetized rats after ganglionic blockade with pentolinium, and atropine sulphate. 3 The reactivity to noradrenaline was significantly lower in parathyroidectomized rats, especially at the beginning of mineralocorticoid treatment. 4 Autotransplantation of parathyroid glands in thyroparathyroidectomized rats re-established normal cardiovascular reactivity and development of hypertension. 5 Cardiovascular reactivity to angiotensin II was not affected in parathyroidectomized rats and was lowered in thyroparathyroidectomized thyroxine-treated rats.


5-Hydroxytryptamine and dopamine transport by rat and human blood platelets. 1 Uptake of 5-hydroxytryptamine (5-HT) by rat platelets in plasma was very rapid and diffusion did not contribute significantly at substrate concentrations that did not saturate the active transport.2 Under conditions which allowed measurement of initial rates of uptake, kinetic analysis revealed a high affinity uptake mechanism for 5-HT (K(m) = 0.7 muM).3 Uptake of dopamine was relatively slow and involved a lower affinity (K(m) = 70 muM) active transport process. Diffusion contributed significantly at concentrations that did not saturate the active transport.4 5-HT competitively inhibited uptake of dopamine, and vice versa; K(i) values for both amines were similar to their respective K(m) values for uptake.5 Chlorimipramine, desmethylimipramine and benztropine were tested as uptake inhibitors. Each was equipotent against 5-HT and dopamine, although the absolute potency of the drugs varied greatly. Chlorimipramine was the most potent (K(i)## 100 nM), and kinetic analysis revealed that the inhibition was competitive against both 5-HT and dopamine.6 Similar results were obtained in studies with human platelets: K(m) values for 5-HT and dopamine were about 1 muM and 100 muM respectively. Activity profiles of inhibitors were also similar: each compound tested was equipotent against 5-HT and dopamine, and the two amines each competitively inhibited uptake of the other.7 We conclude that dopamine is actively transported by platelets via the 5-HT uptake mechanism, but with a much lower affinity. There is no high-affinity dopamine-specific mechanism corresponding to that in the corpus striatum. Consequently although platelets may be valid models of transport in 5-hydroxytryptaminergic neurones, they should not be regarded as models for the dopamine transport mechanism found in dopaminergic neurones.


Effects of end-tidal concentrations of cyclopropane, halothane and diethyl ether on peripheral autonomic neuroeffector systems in the rat. The effects of the inhalation anaesthetics, cyclopropane, halothane and diethyl ether were examined on peripheral neuroeffector systems in the pithed and in the conscious rat. 2 In the absence of a suitable means of accurately quantifying doses of inhalation anaesthetics given to small animals, an apparatus was constructed whereby end-tidal gas samples were collected semi-automatically from the mechanically ventilated rat. 3 Cyclopropane (15.3 and 29.3% end-tidal), halothane (0.20, 0.52 and 0.83% end-tidal) and diethyl ether (2% and 4% end-tidal) lowered the arterial pressure of the pithed rat. Heart rate was increased by diethyl ether 4%, decreased by halothane and unchanged by cyclopropane. 4 While each anaesthetic depressed the pressor responses to sympathetic nerve stimulation, cyclopropane increased and halothane and diethyl ether depressed the pressor responses to exogenous noradrenaline. 5 Each anaesthetic reduced the motor responses of the smooth muscle of the colon to parasympathetic stimulation. 6 The significance of the effects on peripheral neuroeffector systems is discussed in relation to the overall circulatory changes produced by these anaesthetics in the whole animal.


The actions of some vasoactive polypeptides and their antagonists on the anococcygeus muscle. 1 The action of three polypeptides, bradykinin, substance P and eledoisin known to inhibit vascular smooth muscle has been examined on the anococcygeus muscle of the rat, cat and rabbit.2 In the atonic rat muscle, bradykinin and substance P had little or no effect on tone but eledoisin produced a sustained dose-related contraction which could be abolished by phentolamine (1 muM) and is, therefore, probably an indirect sympathomimetic effect. On the motor response to field stimulation of adrenergic nerves, bradykinin had no effect whereas both substance P and eledoisin reduced this response. The mechanism of action was further analysed with eledoisin by examining its effect on the response to noradrenaline. Eledoisin did not alter the dose-response curve to noradrenaline and its inhibitory action is likely, therefore, to be presynaptic.3 In the rat anococcygeus muscle in which the tone was raised by guanethidine or carbachol, bradykinin and substance P reduced this tone whereas eledoisin continued to exert a motor action. Compared with substance P the inhibitory effect of bradykinin appeared at lower concentrations (threshold 0.01 mug/ml), developed more rapidly and the size of the response was greater.4 The effect of bradykinin on the tonically contracted cat and rabbit anococcygeus muscles was examined in addition to that of the rat. In all three species bradykinin caused inhibition and the magnitude of the response was equal to the maximum effect of inhibitory nerve stimulation. None of the peptides affected the inhibitory response to nerve stimulation itself.5 The effects of three substances, hesperitin, khellin and apiin, reported in other tissues to antagonize the action of bradykinin were examined both on the inhibitory response to bradykinin and to field stimulation. None of them was able to inhibit either response, although they reduced tone when given by themselves. During these experiments it was found that ethanol antagonized the inhibitory response to field stimulation.6 The possibility that bradykinin or some related peptide might play a part in the inhibitory response to nerve stimulation in the anococcygeus is discussed.


Uptake and inactivation of prostaglandin E2 methyl analogues in the rat pulmonary circulation. 1 The fate of (15S)-15-methyl prostaglandin E(2) methyl ester and 16,16-dimethyl prostaglandin E(2) in the pulmonary circulation of rat isolated lungs was compared with that of prostaglandin E(2) by means of bioassay.2 Calculated on the basis of height of response of the assay tissues, the inactivation of prostaglandin E(2) was 96 +/- 1%, of 15-methyl prostaglandin E(2) methyl ester, 53 +/- 6% and of 16,16-dimethyl prostaglandin E(2), 50 +/- 4%.3 Responses of the hamster stomach strip to the prostaglandin E(2) analogues passing through the pulmonary circulation were prolonged and slower in onset than those to the analogue given directly to the tissue. No such difference was observed with prostaglandin E(2).4 Bromocresol green, bromothymol blue, bromocresol purple and thymol blue (10(-5) M) all inhibited the inactivation of the three prostaglandins studied, as did diphloretin phosphate (1.5 x 10(-6) M). All five inhibitors also reversed the shape change in response seen after transpulmonary injection of 16-16-dimethyl prostaglandin E(2).5 We conclude that the inactivation of the methyl analogues is due to uptake, as they are not substrates for prostaglandin dehydrogenase.6 The lung may act as a depot for some compounds taking them up from the pulmonary vessels and later releasing them slowly into the systemic circulation.


Comparison of the effects of ultraviolet light and purinergic nerve stimulation on the guinea-pig taenia coli. 1 The responses of the guinea-pig taenia coli, urinary bladder, and the rabbit portal vein to ultraviolet (u.v.) light were compared to those elicited by purinergic nerve stimulation and exogenous adenosine triphosphate (ATP).2 In the presence of sodium nitrite, u.v. light between 340-380 nm produced a maximum relaxation of the taenia coli. The relaxation was reversible and fast in onset. It was unaffected by atropine, guanethidine or low concentrations of phentolamine or propranolol. When the tone was low, the relaxation was usually followed by a ;rebound contraction' upon cessation of stimulation. Thus, the response to u.v. light closely resembles the responses to both purinergic nerve stimulation and exogenously applied ATP.3 U.v. light did not initiate impulses in purinergic nerves since its action was unaffected by tetrodotoxin; nor did it release ATP from nerve terminals (in contrast to its release during purinergic nerve stimulation). The adenosine-uptake inhibitor, dipyridamole, which potentiates the responses to purinergic nerve stimulation and ATP, did not affect the response to u.v. light.4 Agents known to alter postjunctional responses to purinergic nerve stimulation and ATP also altered the response to u.v. light. High concentrations of the 2-substituted imidazoline compounds, antazoline and phentolamine, which antagonize the responses to purinergic nerve stimulation and ATP, reduced the responses to u.v. irradiation. The prostaglandin synthesis inhibitor, indomethacin, which abolishes the ;rebound contraction' following stimulation of purinergic nerves, also blocks the ;rebound ;contraction' following u.v. irradiation. Increases in the K(+) concentration produced parallel changes in the inhibitory responses to u.v. light and purinergic nerve stimulation.5 U.v. light produced relaxation and inhibition of spontaneous activity of the rabbit portal vein (relaxed by ATP), but had no effect on the guinea-pig urinary bladder (contracted by ATP) and ureter (unaffected by ATP).6 It is suggested that u.v. light is acting on some part of the purinergic receptor complex which is involved in the mediation of inhibitory responses to ATP and purinergic nerve stimulation, and may therefore provide a way of investigating the chemistry of inhibitory purinergic receptors.


A study of the sympathomimetic action of guanethidine on the isolated anococcygeus muscle of the rat. Guanethidine, acting on the rat isolated anococcygeus, causes adrenergic neurone blockade (slowly terminated by washing), noradrenaline potentiation and, with higher concentrations, spasm (both rapidly terminated by washing). 2 The spasm is an indirect sympathomimetic action, for it is sensitive to phentolamine and reserpine and shows tachyphylaxis. 3 The concentration of cocaine equieffective with the spasmogenic concentration of guanethidine as an inhibitor of noradrenaline uptake caused much less spasm. Moreover, it did not enhance noradrenaline efflux from anococcygeus loaded with (-)-[3H]-noradrenaline, as guanethidine did. 4 The spasm induced by guanethidine in excess of cocaine is due to guanethidine-evoked noradrenaline release.


Decreased urinary output of tyramine and its metabolites in depression. Despite dramatic clinical improvement in about one-third of a group of severely depressed, medication-resistant patients one year after modified leucotomy, their relative decrease in conjugated and free tyramine output after an oral tyramine load remained unchanged and abnormal. Whilst a direct deficit in intestinal tyramine-conjugating ability still needs to be finally ruled out, this appears most compatible with a deficit due to bodily metabolic failure, perhaps a deficit in membrane transport which could be an essential aspect of the depressive illness syndrome. Attention is drawn to a similar defect in migraine. The two illnesses may represent a common predisposition which an appropriate triggering mechanism may transform to the florid disease. Biochemical detection of such vulnerability may have important diagnostic and predictive significance.


Catechol-O-methyl transferase activity in patients with depressive illness and anxiety states. Erythrocyte catechol-O-methyl transferase (COMT) activity was studied in 65 patients with depressive illness and anxiety states. A hypothesis that measurement of this enzyme might have some value as an aid to diagnosis and as an index of clinical recovery has not been confirmed. In patients with endogenous depression, agitated subjects had COMT levels significantly higher than normal (P less than .01) and retarded subjects had levels significantly lower than normal (P less than .02). These observations are congruent with some reports of high and low urinary MHPG excretion in patients with depression. Further data correlating COMT assays with catecholamine metabolites in depressed patients may reveal homogeneous biochemical subgroups which could serve as a guide to rational therapy.


Gamma-aminobutyric acid (GABA) in the CSF of schizophrenic patients before and after neuroleptic treatment. Gamma-aminobutyric acid (GABA) levels in the CSF were measured in 9 normal individuals, 17 drug-free schizophrenic patients and 10 of these same schizophrenic patients after neuroleptic treatment. There was no significant difference between CSF level of GABA in the control group compared to those in schizophrenic patients; however, 6 of the 7 lowest GABA levels were from schizophrenic patients. There was a significant decline of 12 per cent in mean GABA levels in the CSF after a mean of two months of neuroleptic treatment.


Histocompatability antigens and schizophrenia. The HLA (Human Leucocyte Antigen) types  and B were studied in 80 patients diagnosed as schizophrenic. There was an increased incidence of HLA-BW5 and a decrease in HLA-AW29 and HLA-BW17 as compared with healthy controls. In the sub-group of patients exhibiting Schneider's first-rank symptoms there was an increased incidence of HLA-A1 with a decrease in HLA-A2 and HLA-BW17.


Problems associated with the analysis and interpretation of saliva lithium. The correlation between serum and saliva lithium levels in patients undergoing lithium prophylaxis therapy is discussed. Although a high correlation can be obtained, there is an unacceptably high individual variation of paired results. Two strategies were used in an attempt to improve the reliability of saliva as a predictor of serum levels. A naturally occurring marker in saliva and serum was used. This showed high correlation but still did not prevent large sporadic differences. Serially paired results in individual patients also showed occasional excessive variation. Although saliva lithium has been used for monitoring when serum assessment is impracticable, it is considered that it is, as yet, an unreliable technique.


Variations in the seasonal distribution of births of psychotic patients in England and Wales. The quarterly distribution of births of patients born in England and Wales 1921-60 and first admitted in 1970-75 was examined by decade of birth and by age at year of admission. For patients with schizophrenia and affective psychosis, the distribution varied: in the early decade (1921-30), and for older patients (45-54 years) the proportion of births in the fourth quarter of the year was high, compared with expectation from live births in the general population; but it became lower in succeeding decades and for younger age groups. No comparable change occurred for births of patients with neurosis or personality disorder.


Nineteen cases of morbid grief.

Nineteen cases of morbid grief. Three different patterns of morbid grief are noted. The effect of forced mourning procedures on morbidly grieving patients is discussed with some indication of beneficial and harmful effects of psychotherapeutic intervention.


A clinical scale for the self-assessment of irritability. To date there has been no suitable scale for the self-assessment of irritability in the clinical situation. Existing scales have either included aspects of personality trait together with present state or they have been constructed on non-clinical populations. A self-assessment scale has been constructed which seeks to overcome such faults. Measures of depression and of anxiety are included, together with measures of outwardly directed irritability and inwardly directed irritability. This scale should be known as the Irritability, Depression, Anxiety--or IDA--Scale.


Emotional disturbance in newly registered general practice patients. The General Health Questionnaire has had some popularity as an index of minor psychiatric morbidity and was used in the present study to ascertain the emotional state of newcomers to a practice in a new town. High scorers on the GHQ had more episodes of illness, had more severe ratings of psychological problems, and were more likely to receive a formal psychiatric diagnosis than were low scorers. A second survey one year later confirmed the variability of response to the GHQ inherent in a 'present state' inventory. Doubts are expressed as to the psychiatric nature of the emotional upset measured by the GHQ.


Suicide past and present--the temporal constancy of under-reporting. It is known that official suicide statistics underestimate the incidence of suicide, but it is not clear whether the extent of under-reporting remains constant. An examination of coroners' records in Dublin from 1900 to 1904 and comparison with a similar series in 1964--68 suggests that the underestimation was of similar proportions in both series. It is suggested, therefore, that official suicide statistics are likely to reflect valid temporal changes in suicide and are therefore of value for the study of socio-economic influences on trends in suicide frequency.


Suicide attempts 1970--75: updating a United States study and comparisons with international trends. This paper brings up to date a 1970 study of suicide attempters coming to a major emergency room in an United States urban community and reviews international trends in suicide attempts. Results of the study and the review of the international literature indicate that the high rates of suicide attempts that were observed in 1970 are continuing into 1975. The incidence of suicide attempts continues to be a public health problem primarily amoung young women. Pill ingestion, usually barbiturates and psychotropic drugs, continues to be the most common method used.


The chronicity of schizophrenia in North West India. Results of a follow-up study. The results of a follow-up study of schizophrenics attending a centre in North West India are reported. The relevant literature is reviewed. The results were compared with two well-known studies, one from the United Kingdom and the other from Mauritius. The evidence presented suggests that the course taken by schizophrenia in a newly-developed city and its neighbourhood in this part of India is similar to the one seen in the Western world. This study does not support the view that chronicity of schizophrenia in non-European, non-white populations is different, at least in an urban setting.


Psychiatric decision-making by medical students. Analysis of medical students' formulations and replies to clinical problems indicates difficulty in deciding on the nature and organization of treatment. A programme describing a problem-solving approach was devised, and students taught in this way were shown to be significantly more able to formulate organized treatment plans with more precise aims. It is suggested that problem-solving methods are likely to be much more effective than conventional teaching of psychiatry.


Child observation and assessment centres: psychiatrist' and social workers' difficulties. Two child observation and assessment centres run by a Social Services Department have quickly filled up with older children who stay indefinitely. Many of these children have physical as well as emotional problems and have been admitted as family emergencies in an unplanned way. The paper discusses how, if at all, the psychiatrist called in for advice by social workers can help. This is thought to be a widespread problem.


Radical mastectomy: a 27-year survey.

Radical mastectomy: a 27-year survey. Records of 736 cases of breast cancer presenting to one of the authors (J. D. Y.) have been kept over 27 years. The principles of treatment have remained the same throughout the survey. A radical mastectomy was carried out for stage I and early stage II cases, and when axillary nodes were histologically involved, immediate radiotherapy was given. The 5-, 10- and 15-year survival figures are reported.


Localization of a phaeochromocytoma situated in the pelvis by radionuclide scanning. Accurate localization of an extra-adrenal (pelvic) phaeochromocytoma was achieved by radionuclide scanning using 99 Tcm-Sn-DTPA. This facilitated the planning of the surgical approach and the subsequent removal of the tumour.


Effect of pyloroplasty on gastric emptying: long term results as obtained with a labelled test meal 14-43 months after operation. The mean gastric transit time (t) and the half-time of gastric emptying (t/2) of a labelled test meal have been studied in 18 patients more than 1 year after gastric surgery for peptic ulcer and compared with those in 18 healthy controls. Of the patients, 6 had undergone proximal gastric vagotomy alone (PGV), L had had proximal gastric vagotomy and pyloroplasty (PGVP) and in 6 truncal vagotomy and pyloroplasty (TVP) had been performed. The t and t/2 of patients with PGV alone did not differ significantly from the values of the control group. The t and t/2 in patients after PGVP and TVP, however, were significantly lower than in both controls and patients after PGV alone. There was no statistically significant difference between the groups with PGVP and TVP. The results of this study suggest that the lasting effects of vagotomy operations on gastric emptying are due to the drainage procedure rather than the vagotomy.


The effect of small bowel bypass on diabetes mellitus. The effect of jejunoileostomy on fasting blood sugar, glucose tolerance, hypoglycaemic therapy and weight reduction has been studied in 13 massively obese diabetic patients. The average weight reduction was 36.7 per cent of the preoperative body weight. As a result, 12 patients resumed normal fasting blood sugars and 8 showed normal glucose tolerance tests. A significant improvement in the glucose tolerance tests of the remaining 5 patients was seen. None of the patients required long term hypoglycaemic therapy after the small bowel bypass.


The early diagnosis of non-union of fractures of the tibial shaft by osteomedullography. Osteomedullography (osteomyelography) is a radiographic technique which demonstrates the intraosseous venous circulation. Its use in demonstrating the state of bone healing in fractures of the tibial shaft is described. Its importance lies in the fact that if, 3 months after the initial injury, there is doubt as to the state of union of the fracture, the information gained from osteomedullography allows an immediate decision as to the need for bone grafting. Twenty patients with fractures of the tibial shaft were studied. It was demonstrated that 14 patients had established non-union and 6 patients had delayed union.


Penetrating gunshot wounds of the chest in civilian practice: experience with 250 consecutive cases. Our experience indicates a continued rising incidence of gunshot wounds of the chest in the United States. During the past 4 1/2 years, 250 consecutive cases were treated at the King-Drew Medical Center in Los Angeles. Ninety per cent presented with a haemothorax or haemopneumothorax. Pneumothorax alone was present in only 3 per cent of cases. Twenty per cent had associated intra-abdominal injuries, involving mostly the diaphragm, liver, spleen and the gastrointestinal tract. Eighty per cent were treated with tube thoracostomy and among these there were 2 deaths, neither being related to the chest injury. About 16 per cent underwent thoracotomy with a mortality of 12.8 per cent, all the deaths being caused by severe cardiac wounds. The overall mortality was 2.8 per cent. The complication rate was 5.3 per cent, most complications occurring in patients with associated intra-abdominal and spinal cord injuries. The average period of hospitalization was 6.5 days. The management plan and the indications for the two courses of therapy are discussed.


The pattern of non-diabetic peripheral vascular disease in South India. One hundred and twelve South Indian males with non-diabetic peripheral vascular disease of the lower limb were classified clinically into three groups according to the level of obstruction (aorto-iliac, 26 patients; femoropopliteal, 46 patients; distal, 40 patients). Arteriography was done in 65 patients and serum lipid estimations in 69. In the aorto-iliac group the mean age was 45 years (+/- 11.6 s.d.); 23 per cent had hypertension, 28 per cent polycythaemia and 55 per cent hyperlipidaemia. Aortography suggested atheroma in most. In the femoropopliteal group the mean age was 39 years (+/- 12.8); 22 per cent had hypertension, 11 per cent polycythaemia and 21 per cent hyperlipidaemia. Arteriography showed lesions typical of atheroma in many and was consistent with thrombo-angiitis obliterans in some. In the distal group the mean age was 37 years (+/- 9.8); 8 per cent had hypertension, 20 per cent polycythaemia, 25 per cent hyperlipidaemia and 20 per cent had distal arterial disease of the upper limb. Arteriography was consistent with thrombo-angiitis obliterans in most cases. Atheroma seemed to be implicated in 96 per cent of the aorto-iliac group and in 64 per cent of the femoropopliteal group.


Foreign body in the oesophagus: review of 2394 cases. A total of 2394 patients with a foreign body in the oesophagus was treated in our unit between 1965 and 1976, including 343 children in whom fish bones (146) and coins (134) were most commonly responsible; in adults, bones (fish and chicken) were commonest. Most of the foreign bodies were impacted in the cervical oesophagus. Pharyngoscopy and oesophagoscopy were carried out under general anaesthesia in all cases except those in which the foreign body was ejected spontaneously or when the patient refused the examination. Oesophageal perforation due to a foreign body was encountered in only one child. Two patients in the series developed the fearsome complication of oesophagoaortic fistula.


Peritoneal lavage in appendicular peritonitis. Peritoneal lavage resulted in a significant reduction in the duration of hospital stay in a retrospective series of 189 children with peritonitis secondary to perforation of the appendix. Antibiotic peritoneal lavage also resulted in a significant reduction in the number of children with septic and adhesive complications compared with antiseptic lavage and no lavage, mainly as a result of fewer wound infections. The overall incidence of residual intraperitoneal infection was low, and although differences in this respect were not significant, none of the children treated with antibiotic peritoneal lavage required reoperation for intraperitoneal sepsis.


Peritoneal lavage in faecal peritonitis in the rat. Intraoperative antibiotic peritoneal lavage was significantly better than systemic antibiotic in preventing death from induced faecal peritonitis in the rat. Its efficacy was due to the combined effects of lavage and intraperitoneal antibiotic, each factor alone being significantly inferior to the combined effect of both. Antiseptic lavage was less effective than antibiotic lavage.


Pneumatosis coli: a familial association. A woman and her son who both developed pneumatosis coli within a period of 6 months are described. No familial or cluster association has previously been reported. The aetiology of this uncommon disease is reviewed.


Atopy and immunoglobulin E concentrations in Hodgkin's disease and other lymphomas. Serum immunoglobulin E (IgE) concentrations are increased in Hodgkin's disease (HD) but not in other types of lymphoma. The prevalence of atopic disease is similar to normal in both groups. Patients with high IgE concentrations and HD were separated into atopic and non-atopic groups, which were found to differ clinically. Atopic patients had a significantly lower incidence of night sweats, fever, and weight loss, and treatment had no significant lasting effect on their IgE concentrations. In the non-atopic group there was a striking correlation between high IgE concentrations and a histological appearance of nodular sclerosis, particularly in the presence of night sweats, fever, and weight loss. Successful treatment in the non-atopic group led to a noticeable fall in IgE concentrations, in most cases to normal, though on relapse of the disease they rose again.


Late treatment of paracetamol poisoning with mercaptamine. Forty patients who had taken overdoses of paracetamol were treated with mercaptamine. Twenty-three patients given mercaptamine within 10 hours of poisoning had normal liver function tests at follow-up, and one could not be traced. In 16 patients mecraptamine was begun more than 10 hours after ingestion of paracetamol ("late" mercaptamine). Eight of these patients developed severe liver damage, which in six was moderate or severe before mercaptamine administration. Acute renal failure occurred in two patients; in one other renal function was temporarily severely impaired. At follow-up two patients were not available, and one admitted moribund had died soon after admission. The remaining 13 all had normal liver function tests. It is concluded that late mercaptamine is not dangerous and may prevent further liver damage.


Treatment of malignant ascitic and pleural effusion with Corynebacterium parvum. Six patients with malignant effusions, five from adenocarcinomas and one from a melanoma, were treated by intrapleural or intraperitoneal Corynebacterium parvum. In each case there was a definite reduction in the effusions with a significant decrease in the number of malignant cells; in most cases the effusions stopped completely. Although none of the patients lived for more than a year after treatment, they were undoubtedly more comfortable, as they no longer required frequent paracentesis. In some cases the patients lived for longer than originally expected in a state in which the quality of life was acceptable.


Prognosis of the Ramsay Hunt syndrome.

Prognosis of the Ramsay Hunt syndrome. Thirty-six cases of herpes zoster complicated by facial paralysis (the Ramsay Hunt syndrome) seen over 10 years were reviewed to determine the subjective degree of recovery (ascertained by questionnaire) and residual disability (ascertained by re-examination). Eighteen patients made a full recovery, most within three months; 14 patients were left with only mild residual signs. In only four patients was the final result regarded as unsatisfactory. Outcome was not adversely influenced by age. The facial paralysis of the Ramsay Hunt syndrome thus carries a generally favourable prognosis.


Antenatal diagnosis of thalassaemia major. Haemoglobin synthesis was studied in fetal blood samples obtained at 17 to 20 weeks' gestation in 22 women at risk of carrying a fetus with homozygous beta-thalassaemia. A presumptive diagnosis of homozygous beta-thalassaemia was made in four cases, and the pregnancy was terminated. An inconclusive answer was obtained in one case, and the patient also chose to have her pregnancy terminated. Two fetuses were lost as a result of the procedure. Of the remaining 15 pregnancies, 13 proceeded to term and two to 36 weeks; in each case a normal infant or one heterozygous for beta-thalassaemia was delivered. Current efforts should be directed towards improving the blood sampling technology so that fetal blood sampling can be used widely in those countries where thalassaemia is a major problem.


Organisation of bank of raw and pasteurised human milk for neonatal intensive care. In 1976 a human-milk bank was established at King's College Hospital to serve the neonatal intensive care unit. The bank is staffed by two part-time nurses, who interview prospective donors, organise collections, prepare samples for bacteriological screening, and process the milk. On average 25 litres a month may be collected from about 15 donors, of which at least two-thirds is free enough of bacteria to be fed raw (unheated) to sick and low-birth-weight infants. Most of the remainder may be used after holder pasteurisation. The bank provides an adequate supply of milk of consistent nutritional quality and permits a more informed approach to the dietary management of infants of low birth weight.


Antibody to hepatitis B core antigen in chronic active hepatitis. Antibody to hepatitis B core antigen (anti-HBc), which has been assumed to be a more sensitive indicator of hepatitis B virus replication than hepatitis B surface antigen (HBsAg), was detected in the sera of 26 of our 65 patients with HBsAg-negative chronic active hepatitis. Thus despite the absence of HBsAg the liver disease could be the consequence of chronic infection with hepatitis B virus in these patients. They differed, however, from a group of 35 patients with HBsAg-positive hepatitis in being older on average and having less active liver lesions. The two groups could represent either two stages of chronic infection with hepatitis B virus or two types of response to it.


Hang-gliding accidents.

Hang-gliding accidents. Seventy-five known hang-gliding accidents causing injury to the pilot occurred in the Tyrol during 1973-6. Most occurred in May, June, or September and between 11 am and 3 pm, when unfavourable thermic conditions are most likely. Thirty-four accidents happened during launching, 13 during flight, and 28 during landing, and most were caused by human errors--especially deficient launching technique; incorrect estimation of wind conditions, altitude, and speed; and choice of unfavourable launching and landing sites. Eight pilots were moderately injured, 60 severely (multiply in 24 cases), and seven fatally; fractures of the spine and arms predominated. Six of the 21 skull injuries were fatal. The risk of hang-gliding seems unjustifiably high, and safety precautions and regulations should be adopted to ensure certain standards of training and equipment and to limit flying to favourable sites and times.


Diabetic cardiomyopathy? An echocardiographic study of young diabetics. An echocardiographic study was carried out on 23 young diabetics, 19 of whom had retinopathy. Their diastolic function was analysed by comparing the timing and pattern of mitral valve opening with the pattern of left ventricular wall movement. Only six patients had all their values within the normal range. Fourteen patients had abnormalities similar to those seen in patients with cardiomyopathy; the close time relation between mitral valve movement and wall movement was lost and mitral valve opening delayed in eight patients. Three other patients had considerable outward wall movement before mitral valve opening, which is characteristic of ischaemic heart disease. Although these studies provide no definite evidence of a cause, the abnormalities found may reflect a subclinical diabetic cardiomyopathy due to small-vessel disease.


Consultant physician to outpatients.

Consultant physician to outpatients. Analysis of the records of the last 450 outpatients referred to me showed that the basic disorder of at least one in three lay in the psyche, and there was a large emotional element in many of the others. None were put on a waiting list for admission. Not only should physicians be generalists most of the time (whether or not they have a special interest) but most medical problems are best dealt with by the GP. Only occasionally can the physician attach a precise diagnosis to a patient who has been an obscure problem to his GP, and the physician's most important function is to reassure the patient and explain his symptoms. Routine investigations seldom benefit the patient. If there could be a more equitable distribution of GPs of high quality with good back-up facilities fewer general and many fewer specialist physicians would be needed.


Choosing the programme for an international congress. The method of selecting abstracts for an international congress at which only 15% of submitted papers could be accepted entailed a panel of 12 assessors using their specialised knowledge, but presentation of the abstract was also important is selection. There was only a limited agreement between assessors in arranging abstracts in order of merit, so that a single assessor would be unacceptable. Use of the full panel to grade all abstracts was very expensive, but it could be replaced, without unacceptable injustice, by dividing the work randomly among groups of three selectors.


Noradrenaline neuron innervation of the neocortex in the rat. Noradrenaline innervation of the rat neocortex is studied by glyoxylic acid histochemistry and radioisotopic biochemical analysis. The data indicate that all neocortical areas receive a noradrenergic innervation which is identical in organization but varies in density from area to area. Radioisotopic analysis of catecholamines in the cortical areas studied reveals only the presence of significant levels of noradrenaline. Unilateral locus coerulus ablation greatly diminishes ipsilateral noradrenaline content and fiber innervation in all neocortical areas studied. Detailed histochemical analysis reveals a diffuse plexus-like arrangement of noradrenaline fibers, with each cortical layer having a distinctive pattern of innervation. Single noradrenergic fibers enter layer VI of cortex and branch at all levels to undergo extensive collateralization. Terminal horizontal branching in the molecular layer results in the most dense fiber plexus of all cortical layers. This pattern of noradrenaline innervation is similar to that of other non-specific afferent systems innervating neocortex.


Hippocampal connections and spatial discrimination. Rats were tested in a new spatial discrimination procedure which measured working memory. Following preoperative testing, lesions were placed to disrupt each of the major extrinsic fiber connections of the hippocampal formation. Destruction of the entorhinal area, body of the fimbria-fornix anterior to hippocampus, septum, or postcommisural fornix produced a severe and consistent impairment in performance. Analysis of error patterns indicated that when animals with limbic lesions made errors, they were likely to make these errors in the same sequence as the original choices. These data support the hypothesis that the hippocampus has an important role in the processing of information about spatial location, and that normal performance on this task requires an intact hippocampal circuitry.


An investigation of the cerebellar cortico-nuclear projections in the rat using an autoradiographic tracing method. I. Projections from the vermis. The topography of the projections from the vermis of the cerebellar cortex to the intracerebellar nuclei (excluding the vestibular complex) was newly investigated in the rat using an autoradiographic technique. The projection were strictly ipsilateral and the majority terminated in nucleus fastigus although there were small projections to the medial pole of nucleus interpositus. The only portion of fastigius which was never heavily labelled was the dorsolateral protuberance. Some rostrocaudal localisation was evident with lobules II-V projecting to rostral fastigius (Fm), lobules VI-VIII projecting mainly more caudally (Fcm and Fm) and lobule IX projecting to the caudoventral tip of fastigius. Nevertheless, even the densest portions of the terminal fields often overlapped heavily, suggesting that, in the rat, in contrast to some other species, the rostrocaudal localisation is such that individual lobules do not possess private termination fields of any extent. Such an arrangement should provide ample opportunity for integration by individual nuclear neurones of input from extensive areas of cortex. In the mediolateral plane, localisation was more evident, with the medial vermis projecting to the medial pole of fastigius and the lateral portion to lateral fastigus and less heavily to medial interpositus.