Effects of serum-free culture media on human liver and fibroblastic cells. The morphological aspects and amino acid variations of human fibroblast and liver cell monolayer cultures were studied in serum free media. Under these conditions, the behaviour of the two cell types differed greatly. The morphological changes for the liver cells, as compared with the fibroblasts, appear more quickly and some of these changes are particular. Furthermore, extracellular amino acid variations are of lesser importance for the liver cells, during the 10 days following the suppression of serum, except for serine.


Monodomain samples of dipalmitoyl phosphatidylcholine with varying concentrations of water and other ingredients. Methods are presented for the preparation of large monodomain phospholipid bilayer arrays containing variable amounts of water approaching the two-phase limit. The optical birefringence of these lamellar phases of dipalmitoyl phosphatidylcholine (DDPC) is measured over a range of temperature and water content, and phase transitions are observed. The techniques employed for pure DPPC and water are extended in order to produce macroscopically aligned samples containing varying concentrations of cholesterol, inorganic salts, antibiotics, and chlorophyll a. Polarization studies of the 670-nm band of chlorophyll a indicate macroscopic orientational order in the chromophore under the same conditions.


An extrapolation method for reducing equilibration times in sedimentation equilibrium experiments. We present a detailed investigation of the use of an extrapolation technique to decrease running times of sedimentation equilibrium experiments. If concentration profiles are available at time delta tau, 2delta tau, 3delta tau,...., cn(r) = c(r, n delta tau), then the Aitken transformation replaces the cn(r) + ĉn(r) = [cn + 1(r) cn - 1(r) - c2n(r)]/[cn + 1(r) + cn - 1(r) - 2cn(r)]. We show that the ĉn(r) converge to the equilibrium values c infinity (r) much more quickly than the cn(r). Savings in time are shown to range from a factor of approximately 2 for meniscus depletion experiments to factors of between 4 and 8 for lower speeds or smaller molecular weights. It is also shown that the technique is quite sensitive to noise, so that an accurate optical system is required to allow its optimal use.


Hydration of phosphatidylocholine. Adsorption isotherm and proton nuclear magnetic resonance studies. Adsorption-desorption isotherms were obtained for water binding by 1,2-dimyristoylphosphatidylcholine in the temperature range 15 degrees-35 degrees C. The isotherms were analyzed by Brunauer et al.'s (BET) theory and also a polarization theory, the latter being more successful in fitting the data. There was some evidence for a change in the surface field of the lipid bilayer around 25 degrees C. Proton T1 and T2 measurements were used to obtain a log-normal molecular correlation time distribution for water protons in these systems. This distribution was compared with the isotherm data to effect a description of several classes of water molecules.


Human red cell hemolysis rates in the subsecond to seconds range. An analysis. Hypoosmotic shock kinetics of the normal human red cell (25 degrees C) were investigated by means of a rapid kinetics apparatus, with a resolving time of about 50 ms. The results are compared with some current models for hemolysis. The fast hemolysis plots are not true symmetric sigmoids, in contrast to results from less stressful conditions, nor can they be simply fitted to an "all or none" process. In the most severe conditions, mixing with neat water, the velocities with which red cells start to hemolyze depend on the rate at which the cell is converted to a swollen sphere (lag phase). Under such conditions, the mean time to rupture and start of leaking is about 0.6 s. The rate of osmotically driven solvent flow is probably the principal controlling factor in the discocyte to sphere transformation. The overall course of hemolysis can be described in terms of two rate processes and a distribution of cell fragilities. The fragilities probably depend on the age of individual cells in the samples. In the low-salt region, the effect of hypotonicity as well as hypoosmolality is discerned. The surface charge on the red cell provided no driving force for rupture above salt concentration 0.10M, but at 0.05 M salt and below, electrostatic effects may contribute.


Physics of chemoreception.

Physics of chemoreception. Statistical fluctuations limit the precision with which a microorganism can, in a given time T, determine the concentration of a chemoattractant in the surrounding medium. The best a cell can do is to monitor continually the state of occupation of receptors distributed over its surface. For nearly optimum performance only a small fraction of the surface need be specifically adsorbing. The probability that a molecule that has collided with the cell will find a receptor is Ns/(Ns + pi a), if N receptors, each with a binding site of radius s, are evenly distributed over a cell of radius a. There is ample room for many indenpendent systems of specific receptors. The adsorption rate for molecules of moderate size cannot be significantly enhanced by motion of the cell or by stirring of the medium by the cell. The least fractional error attainable in the determination of a concentration c is approximately (TcaD) - 1/2, where D is diffusion constant of the attractant. The number of specific receptors needed to attain such precision is about a/s. Data on bacteriophage absorption, bacterial chemotaxis, and chemotaxis in a cellular slime mold are evaluated. The chemotactic sensitivity of Escherichia coli approaches that of the cell of optimum design.


Side-chain mobility and the calculation of tyrosyl circular dichroism of proteins. Implications of a test with insulin and des-B1-phenylalanine insulin. Previous calculations using crystal structure coordinates (Strickland and Mercola [1976], Biochemistry. 15: 3857) have predicted that about 40 percent of the calculated tyrosyl circular dichroism of hexameric insulin is due to one of the four tyrosine residues: viz. the A14-tyrosine interacting with the nearby B1-phenylalanine ring group. We have tested this prediction by measuring the tyrosyl circular dichroism of an isomorphous analogue of insulin, des-B1-phenylalanine-insulin. Contrary to expectation, the resulting circular dichroism was the same as that of insulin. It is concluded that the B1-phenylalanine residue does not in fact make a large contribution to the circular dichroism of A14-tyrosine. This result is probably due to the thermal motion of the B1 and A14 ring groups not taken into account by the calculations. An example of the effects of thermal motion on the calculated circular dichroism is given and improvements that do take into account thermal motion are discussed.


Thermal-stimulated pressure and current studies of bound water in lysozyme. The state of bound water in crystalized lysozyme was studied by four techniques: electret thermal depolarization currents, thermal-stimulated pressure, isothermal polization decay, and thermogravimetry. Hydration levels ranged from 0 to 40 mg water/g protein. Desorption of bound water dipoles was found to be the main process responsible for electrical depolarization. Two different binding sites for water were identified with long relaxation times at room temperature (order 10(2)s) and activation energies of 0.34 plus or minus 0.02 eV and 0.55 plus or minus 0.04 eV.


The representation of membrane admittance. An integral representation for the membrane admittance in terms of its known current response to a voltage step function is presented. It is demonstrated that the frequency-dependent terms in the contribution to the membrane admittance by the ion-selective conductance of the nerve membrane are proportional to the static conductances. The additional information contained in the real and imaginary parts of the membrane admittance should allow the parameters of the ion conductance to be determined. Eventually, these measurements should also give information about the electric dipole displacement currents of the conductance systems themselves, and about the metabolically supported active ion transport currents that maintain the ion concentration gradients.


A field-dissociation relation for polyelectrolytes with an application to field-induced conformational changes of polynucleotides. An extension to polyelectrolyte solutions of Onsager's field-dissociation relation for weak electrolytes can be derived in a simple way. It is found that, except in the limit of zero ionic strength, a strong applied electric field prevents counterion condensation from proceeding to completion. The extent of incompleteness initially varies linearly with the applied field. The field-dissociation relation can easily be incorporated into the theory of ionic effects on the stability of ordered polynucleotide structures, whereupon a dependence of the stability on field strength emerges. An explicit calculation for a co-operative transition of the DNA melting type is presented, and it is concluded that for sufficiently low ionic strengths, a field of the order of 10 kV/cm may be able to induce melting by lowering the Tm by a few degrees. The threshold effect found experimentally by Pörschke, and particularly the observed linear dependence of the threshold field on the logarithm of the ionic strength, appears here as a simple consequence of the linear increase of the stabilization free energy with the logarithm of ionic strength.


Dielectric studies on self-associating nucleosides and bases in aqueous solution. Measurments have been made of the dielectric properties of aqueous solutions in which aggregates are formed by stacking. The nucleosides cytidine, uridine and thymidine, and the bases purine, pyrimidine and 6-methylamino-9-methyl-purine (N6,N9-dimethyladenine) were investigated at around 1 MHz, where the static increments can be determined, and for cytidine, dimethyladenine, uridine and pyrimidine measurements were also made in the 100-2000 MHz range where the main relaxation of the solute dipoles is found. Whereas cytidine and purine show a positive static dielectric increment increasing linearly with concentration, dimethyladenine, uridine, thymidine and pyrimidine show a similar negative effect. Also, within the experimental accuracy, single relaxation times are found for the solute dispersions investigated. It is suggested that these relaxations correspond to the effects of free rotation of individual polar molecules in the plane of stacking. This phenomenon would also account for the linear variation of the dielectric increments with concentration. These increments are thought to be positive or negative due to the varying balance in the solutions between the loss of polarization due to displaced and "bound" water and the corresponding gain due to the polarity of the solute molecules.


A calorimetric investigation of single stranded base stacking in the ribo-oligonucleotide A7. Differential scanning calorimetry has been employed to determine the energy change associated with single stranded base stacking in the ribo-oligonucleotide A7. A total enthalpy change of 20.3 kcal (mole of heptamer)-1 was measured. This corresponds to 2.9 kcal (mole of adenine)-1 or 3.4 kcal (mole of A-A stack)-1 if one assumes that all six stacking interactions are energetically equivalent. These results represent the first direct determination of this important parameter for a ribo-oligonucleotide. It is noted that the calorimetrically determined value reported here is considerably lower than any of the previously published van't Hoff enthalpies but is consistent with values that can be derived from other calorimetric data.


Relaxation kinetics of the helix-coil transition of a self-complementary ribo-oligonucleotide: A7U7. Relaxation measurements on the kinetics of the double helix to coil transition for the self-complementary ribo-oligonucleotide A7U7 are reported over a concentration range of 6.9 micrometer to 19.6 micrometer in single strand in 1 M NaCl. The rate constants for helix formation are about 2 X 10(6) M-1 s-1 and decrease with increasing temperature yielding an activation enthalpy of -6 kcal/mole. The rate constants for helix dissociation range from 3 to 250 s-1 and increase with increasing temperature yielding an activation enthalpy of +45 kcal/mole. The kinetic data reported here for 1 M NaCl is compared with previously published results obtained at lower salt concentrations. These data are discussed in terms of the quantitative effect of ionic strength on the kinetics of helix-coil transitions in oligo- and polynucleotides.


The circular polarization of fluorescence of the ionophore lasalocid A(X-537A) and some of its metal complexes. The conformation of the ionophore lasalocid A (X-537A) and its complexes with metal ions was probed by the circular polarization of their luminescence (CPL). The CPL of each complex in methanol was found to be different than when in n-hexane. Furthermore, the different metal ion complexes investigated had a different CPL spectrum in each solvent. These findings indicate wide variability in the conformation of the complexes depending on the metal ion and the solvent. From the spectral behaviour of the CPL it was concluded that at least some of the complexes exist in more than one form in solution. A comparison between the CPL and CD spectra indicates a change in the conformation of the ionophore in the vicinity of the salicylate chromophore upon electronic excitation.


Equivalency of linear least squares curve fitting and reciprocal functions in protein circular dichroic spectra analysis. Two methods for the analysis of the circular dichroism spectra of proteins for determination of secondary structure have been examined. These are the linear curve fitting of the data, minimized in the least squares sense, and the method of reciprocal functions proposed by C.C. Baker and I. Isenberg, Biochemistry 15 (1976) 629. It is shown that the use of these two methods give results that are identical, providing the same set of reference spectra are used in each case, and, therefore, that no new information is obtained by the use of either one over the other.


Consecutive immobilized enzymatic reactions with and without enzyme denaturation. Consecutive biochemical reactions in an immobilized enzyme particle under the effects of internal and external diffusional resistances are analyzed. A rigorous nonlinear reaction kinetics is employed and the steady state effectiveness factor with negligible enzyme denaturation compared with the previous prediction by the first-order kinetics. It is found that the difference between them is rather substantial under most circumstances. The cases with significant enzyme denaturation are also investigated by using an unsteady state model. The substrate concentration responses to variation of the physical and kinetic parameters reveal many interesting characteristics of the reaction system.


Quinoxalinol derivatives of aliphatic 2-oxocarboxylic acids. Infrared and mass spectra of the O-trimethylsilylated compounds. In acidic media o-phenylenediamine and 2-oxoacids react to yield quinoxaline derivatives. On derivatization in pyridine with silylating reagents quinoxalinol-O-TMS ethers or O-TMS-ether-TMS-esters are formed exclusively as shown by gas chromatography infrared spectrometry and gas chromatography mass spectrometry. These derivatives have very favourable properties for gas chromatographic detection and quantitation of the parent 2-oxoacids. The mass spectra have characteristic fragments which facilitate easy identification. In addition, 'single ion monitoring' of all aliphatic 2-oxoacids can be performed with only three fragments at m/e 217,232 and 245. In some aspects the mass spectra resemble those of other heterocyclic compounds which contain an O-alkyl sidechain. The fragmentation mechanisms were deduced by low resolution mass spectrometry with and without deuteration, high resolution mass spectrometry and metastable ion evidence. A new type of rearrangement alpha-beta-elimination of ethylene or propylene from the aliphatic sidechain, is proposed for some O-TMS quinoxalinols.


MASSFORM: a computer program for the assignment of elemental compositions to high resolution mass spectral data. This paper describes a computer program which calculates all possible empirical formulas for each accurately measured mass in a high resolution mass spectrum. The program, MASSFORM, incorporates a novel mechanism for classifying the empirical formulas generated according to their empirical formula. This mechanism makes it possible to use a set of general empirical formulas to aid in the analysis of complex mixtures in much less time than most other such programs. The program is being used as an important aid to environmental studies.


Mass spectrometric characterization of activated N-(2-chloroethyl)amino oxazaphosphorine derivative. The hydroperoxy and several alkylthio derivatives of the antitumor agents cyclophosphamide (2-bis(2-chloroethyl)amino tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide), ifosfamide (3-(2-chloroethyl)-2-(2-chloroethylamino)tetrahydro-2H-1,3,1-oxazaphosphorine 2-oxide) and trofosfamide (3-(2-chloroethyl)-2-(bis(2-chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide) were characterized by electron impact and field desorption mass spectrometry. The compounds, which are stabilized derivatives of the activated hydroxylated intermediates of cyclophosphamide (ifosfamide, trofosfamide), could be identified as 4-hydroperoxy and 4-alkylthio oxazaphosphorines. The existence of diastereomers of these products was demonstrated by thin-layer chromatography and f.d. mass spectra. Derivatization with benzylmercaptan was found to be an appropriate method for the quantitative isolation and mass spectral identification of the activated metabolic intermediates of cyclophosphamide from biological material. Using this reaction, 4-hydroxycyclophosphamide and its acyclic tautomer, aldophosphamide, which are too unstable for direct identification, were detected in urine and serum of patients treated with 3H-cyclophosphamide.


Location of functional groups with the aid of mass spectrometry. XVI.--Mass spectra of trimethylsilylated androstan-3,16,17 beta-triols. The mass spectra of androstan-3,16,17beta-triols are very similar, so that a distinction between isomers is rather difficult. Main degradation reactions correspond to expulsion of substituents and loss of parts of the D-ring system.


Mass spectrometric studies of twenty-one metabolically important acylglycines. The mass spectra of the methyl esters of twenty-one metabolically important N-acylglycines are reported. The spectra are discussed in terms of their fragmentations and their application to studies of metabolic diseases. In particular, the high relative abundance of the peak at m/e 30 in the spectra of many aliphatic acylglycine methyl esters was studied by using ([2,2-2H2]propionyl)glycine and high resolution mass spectrometry. This fragment was assigned to the even-electron ion [CH2 = NH2]+.


Characterization of diastereomeric and enantiomeric ephedrines by gas chromatography combined with electron impact mass spectrometry and isobutane chemical ionization mass spectrometry. The diastereomeric hydroxyamines, ephedrine and psi-ephedrine, were well differentiated by gas chromatography of their N-acetyl O-trimethylsilyl derivatives. For the analytical separation of enantiomers, conversion into N-(R)-alpha-phenylbutyryl O-trimethylsilyl derivatives was effective in the cases of ephedrine, psi-ephedrine and nor-psi-ephedrine (but not that of nor-ephedrine, on the two stationary phases used). Electron impact mass spectra showed structurally diagnostic fragmentations, but the two diastereomeric amides from each pair of enantiomers yielded generally similar spectra. Molecular ions were of low abundance, but under chemical ionization conditions (isobutane) abundant protonated molecular ions were produced.


Mass spectrometric and nuclear magnetic resonance confirmation of a 3,3-spirocyclic indole derivative formed from melatonin and related acyl tryptamines. When melatonin is reacted with pentafluoropropionic anhydride for selected ion monitoring or electron capture gas chromatographic analysis a volatile product results. Examination of the product by combined gas chromatography mass spectrometry has established that the molecular weight of 360 corresponds to the addition of one molecule of pentafluoropropionic acid followed by dehydration. Further spectroscopic and chemical examination using mass spectrometry and nuclear magnetic resonance with isotopic labelling has established that the product is a 3,3-spirocyclic indole derivative. Several analogous compounds were also examined and their mass spectra studied.


Mass spectrometric determination of new prostaglandin derivatives (series A and E). The reaction of prostaglandins E1, E2, A1 and A2 with a 1:1 mixture of N,O-bis-trimethylsilyltrifluoroacetamide and piperidine favours the quantitative enolization of the 9-keto group of prostaglandins E, thus giving the corresponding tetrakis-TMS derivatives with molecular ions at m/e 642 and m/e 640 for prostaglandins E1 and E2, respectively, and also gives a new type of prostaglandin A-piperidyl-TMS derivative characterized by very strong base peaks at m/e 464 and 462, with molecular ions at m/e 637 and 635 for prostaglandins A1 and A2, respectively. The probable reaction mechanisms prevailing in both cases are discussed in accordance with the low and high resolution mass spectral data presented.


Analysis of drugs by pyrolysis. I. Selected ion monitoring combined with a pyrolysis method for the determination of carpronium chloride in biological samples. In order to establish an analytical method for carpronium chloride, a parasympathomimetic agent, the pyrolysis reaction of carpronium chloride was examined in a g.c.m.s. system, which revealed that gamma-butyrolactone was produced directly from the drug as the main pyrolysis product. In the case of conversion of [2,2,3,3-2H4]carpronium chloride into the deuterated gamma-butyrolactone, 2H/1H scrambling was observed and confirmed to occur during the pyrolysis process of the deuterated compound. The proportion of gamma-[2H4]butyrolactone among the pyrolysis products was almost independent of the operating conditions, so [2,2,3,3-2H4]carpronium chloride was of practical use as an internal standard for selected ion monitoring. By incorporation of the pyrolysis reaction of carpronium chloride with selected ion monitoring and the use of [2,2,3,3-2H4]carpronium chloride as an internal standard, a rapid, sensitive and selective method was devised for the determination of the drug in biological samples. The method was utilized successfully for the biopharmaceutical studies of carpronium chloride in ma.


The measurement of acetanilide in plasma by spectrophotometric and selected ion monitoring methods. Plasma samples from volunteers who had received an oral dose of acetanilide have been analysed by gas chromatography mass spectrometry and ultraviolet absorption techniques. The gas chromatography mass spectrometry method involved extraction of the plasma and analysis of the acetanilide using selected ion monitoring with a deuterated internal standard. In the ultraviolet method the plasma was hydrolysed with acid to convert the acetanilide to aniline, and this compound was diazotized and coupled with N-1-naphthylethylene-diamine. The absorbance of the resulting complex was read at 550 nm. Acetanilide levels in plasma determined by the selected ion monitoring method were significantly lower than those measured by spectrophotometry. Pharmacokinetic data calculated from the results obtained using these two assays are very different and illustrate the need for an accurate and specific method of analysis. The major metabolites of acetanilide are shown not to interfere with these assays and the results suggest the possible presence of a new metabolite of acetanilide.


Gas chromatography chemical ionization mass spectrometry of prostaglandin Falpha cyclic boronate derivatives. The electron impact mass spectra of prostaglandins F 1alpha, F 2alpha and F 3alpha methyl ester cyclic 9,11-methane-, n-butane-, cyclohexane- and benzeneboronate 15-trimethylsilyl ethers show base peaks corresponding to [M-(C-16-C-20)]+, i.e. [M-71]+ for prostaglandins F 1alpha and F 2alpha but [M-69]+ for prostaglandin F 3alpha yielding identical ions in the latter two cases. Derivatives of prostaglandin F 2alpha and F 3alpha are difficult to separate by gas chromatography, so that the use of this ion type for single ion monitoring of either prostaglandin (as has been reported) is ambiguous. The chemical ionization mass spectra of these cyclic boronates, however, show distinctive base peaks for prostaglandins F 1alpha, F 2alpha and F 3alpha at m/e 317,315 and 313 respectively, corresponding to [M-RBO2H2-TMSO]+. Fragmentation patterns have been investigated by the use of [3,3,4,4-2H4]prostaglandin F 2alpha and by the formation of [2H9]trimethylsilyl ethers and a [2H3]methyl ester. Cleavage of the C-15-C-16 bond is of minor importance under chemical ionization conditions. The possible value of the [M-RBO2H2-TMSO]+ ions for single ion monitoring is explored: specificity is aided by the formation of the same ions from a series of boronates of characteristic retention indices.


Hydantoin ring glucuronidation: characterization of a new metabolite of 5,5-diphenylhydantoin in man and the rat. A new metabolite of 5,5-diphenylhydantoin has been found in human urine and in rat bile. This new metabolite arises by direct glucuronidation of 5,5-diphenylhydantoin (i.e. no prior aryl hydroxylation occurs) and is characterized as the N-3 glucuronide. This structure assignment is based on (a) study of mass spectra of permethyl, perdeuteriomethyl, N-methyl-per-O-deuteriomethyl and deuteriomethyl ester permethyl derivatives and (b) comparison of the reactions of the new glucuronide metabolite and 5,5-diphenyl-3-methylhydantoin with diazomethane. Prominent ions at m/e 322 and 378 in the mass spectrum of the permethylated derivative of the glucuronide metabolite arise via retro Diels-Alder reactions of the glycone ring.


Analysis of hexosaminitol-containing disaccharide alditols from rat brain glycoproteins and gangliosides as O-trimethylsilyl derivatives by gas chromatography mass spectrometry. The O-trimethylsilyl derivatives of five reference disaccharide alditols composed of a N-acetylhexosaminitol substituted at C-3, C-4 or C-6 with a hexose moiety were studied by gas chromatography mass spectrometry. The data were used in the determination of the linkage in disaccharide alditols derived from rat brain glycoproteins and gangliosides. The O-glycosidically linked carbohydrate units of brain glycoproteins contained two oligosaccharides, alpha-galactosyl-(1 leads to 3)-N-acetylgalactosaminitol and beta-galactosyl-(1 leads to 3)-N-acetylgalactosaminitol, whereas only the latter was obtained from brain gangliosides after partial acid hydrolysis and reduction.


Phosphazenes: high molecular weight reference compounds for field desorption mass spectrometry. Because of poor field ionization sensitivity or an insufficient number of peaks, conventional reference materials are inadequate for field desorption mass spectrometry. Hexakis (multifluoroalkoxy)cyclotriphosphazenes satisfy a growing need for high molecular weight reference compounds amenable to either electron impact or field ionization. In comparison with tris(perfluoroalkyl)-s-triazine standards, the substituted phosphazenes offer greater volatility, easier synthesis and better mass spectral characteristics. Phosphazene mixtures, in particular, cover a broad mass range in either ionization mode, creating new measurement capabilities for ions at high masses.


Metabolism of DL-[14C]prenylamine in man. Following oral administration of DL-[14C]prenylamine, about 40% of the dose administered was excreted in urine within 10 days. Less than 0.1% of the dose was excreted as unchanged prenylamine. The drug was extensively metabolized to at least 20 to 25 metabolites. The structure of 12 metabolites could be elucidated by means of g.c.m.s. Ring hydroxylation and further methylation of the phenolic metabolites are the main metabolic pathways involved. A substantial part of the drug and/or its metabolites is metabolized via cleavage of the C--N--C bond, giving rise to amphetamine and diphenylpropylamine which are further metabolized by aromatic and sidechain hydroxylation.


The mass spectra of 8-azapurines.

The mass spectra of 8-azapurines. The mass spectra of 8-azaadenine, 8-azahypoxanthine, 2,6-diamino-8-azapurine, 8-azaxanthine and 8-azaguanine are all characterized by intense molecular ion peaks. Fragmentation pathways are advanced to account for the other ions observed in the mass spectra and are supported by metastable transitions, accurate mass measurements and deuterium labelling studies. 8-azaadenine and 8-azahypoxanthine fragment initially by elimination of nitrogen from the molecular ion, but this is a minor process with the other compounds. In many respects the electron impact induced fragmentation of the 8-azapurines is analogous to that of the corresponding purine derivatives.


Identification of hydroxyhalobiphenyls as their methyl ethers by gas chromatography mass spectrometry. The mass spectra and gas chromatographic properties of 17 synthetic fluoro-, chloro- and bromomethoxy-biphenyls and 12 dichlorodimethoxybiphenyls have been examined. From this representative series it appears that the position of the methoxy group (ortho, meta and para to the biphenyl bond) in all monomethoxy compounds examined, and the positions of the two methoxy groups in most of the dimethoxy compounds, can be assigned unambiguously by their difference in fragmentation pattern. The value of this method was shown by metabolism experiments in which 4,4'-difluoro- and 4,4'-dibromobiphenyl were fed to rats and 4,4'-dichlorobiphenyl was administered to plants. All hydroxylated metabolites found were identified by gas chromatography mass spectrometry. Relationships between structure and gas chromatographic retention time of these compounds are discussed.


Determination of bupivacaine in human fetal and neonatal blood samples by quantitative single ion monitoring. The blood levels of bupivacaine administered epidurally during labour have been determined in mother, fetus and the newborn infant by quantitative single ion monitoring, following gas chromatographic separation. Concentrations were determined from the height of the peak obtained at m/e 140 derived from bupivacaine compared with that at m/e 154 derived from the internal standard, 1-n-pentyl-2-(2',6'-xylylcarbamoyl)piperidine. Results from six mothers and their infants showed that the drug passed rapidly from the maternal circulation to the infant. The plasma half-life of the drug in the newborn infant was 18 h compared with 1.25 h for the adult.


Studies of molecular species of fetal lung lecithins by gas-liquid chromatography mass spectrometry. The molecular species of lung lecithins obtained from rabbit and rat fetuses at different days of gestation and from newborns were analysed as TMS derivatives of the corresponding diglycerides in a gas chromatograph mass spectrometer system by selected ion retrieval. In the latter part of gestation, the order of the main molecular species of lung lecithins, PCn, was PC32 greater than PC34 greater than PC30, while at an earlier stage it was PC34 greater than PC32 greater than PC30. During gestation the change of PC32:0, dipalmitoyllecithin, was remarkable. Ether lecithins are also discussed.


[Autonomic reactions arising during skeletal muscle contraction in freely moving cats]. Cardiovascular responses, evoked by n. gastrocnemius stimulation, were studied in intact cats with implanted electrodes. Non-noxious m. gastrocnemius contraction caused a rise of blood pressure and tachycardia. During curarization painless and threshold painful nerve activation failed to lead to vegetative shifts. The reflex vegetative responses during muscle contraction in intact animals may be used as a model of hemodynamic and respiratory changes in man during muscle exercise.


[Blood pressure reflexes to stimulation of tibial nerve A fibers in mesencephalic and bulbar cats]. In bulbar and mesencephalic unanesthetized cats, as well as in anesthetized cats with intact brain the role of impulses of different tibial nerve A-fiber subgroups (electrical stimulation at a frequency of 10 S--1) in the reflex changes of arterial pressure was studied. The lowest thresholds were registered in anesthetized cats with intact brain, the highest -- in the bulbar ones. In the former the A-fiber excitation evoked only depressor reflexes. In some of the bulbar and mesencephalic animals only pressure reflexes originated. In this experimental series the reflexes in mesencephalic cats were nearly maximal when the fibers with conduction velocity of over 15 m/s were excited. In bulbar cats it was necessary to excite also the thinner A-fibers for such an effect. Thus, the exclusion of suprabulbar structures in unanesthetized cats lowered the sensitivity of the central mechanism of vasomotor regulation to the impulses from the low-threshold A-fibers. This influence is not apparent in the other group of experiments where depressor reflexes occurred only on stimulation of A-fibers with high conduction velocity. In these experiments stimulation of A-fibers with lower conduction velocity also evoked pressor reflexes, but the difference in their value in bulbar and mesencephalic cats was insignificant.


[Segmental reciprocal reflexes of the thoracic region of the spinal cord]. Under conditions of routine experiment stimulation of the central cut end of the intercostal nerve evoked reflex discharges simultaneously in several intercostal nerves of the same and contralateral side of the thorax. No reciprocity in these reflexes was noted. In the present experiments it was shown (that in unanesthetised spinal cats the reflex discharges in the intercostal nerves were facilitated by the mechanical stimulation of the ipsilateral parietal pleura and were inhibited by the same kind of stimulation of the contralateral pleura. Thus, the existence of the reciprocal segmental reflexes between the left and the right sides of the thorax was established for the first time.


[Gas exchange and hemodynamics following complete replacement of blood with a solution of purified hemoglobin]. Complete exchange blood substitution (down to hematocrit level of 1--3%) by 7--8% solution of hemoglobin (Hb) completely free of stromas and procoagulant activity of human hemoglobin was performed in cats. The Hb solution is capable of carrying oxygen and maintaining the life of the animal with a complete blood loss for some time. The Hb solution is readily saturated with oxygen in the lungs and releases oxygen in the tissues, although to a significantly lesser degree than Hb in the red cell; besides, the Hb solution maintains the basic value of hemodynamics for some time.


[Dynamics of transcallosal potentials following local exposure of the cerebral cortex to high temperature]. Experiments were conducted on cats, anesthetized with nembutal. The influence of local heating of the sensomotor cortex on the transcallosum response was examined. It was revealed that heating for short and long periods of limited regions of the cortex of both hemispheres induced a primary depression of the negative component of the transcallosum response at 44 degrees C and above it. The depression was replaced by an irreversible block of both response phases at 47--49 degrees C. It was concluded that the direct inhibitory influence of high temperatures on the cortical neurons was expressed only within the range of extreme temperature incompatible with vital activity of the whole organism. Experiments with the thermal block of the hemisphere region could testify to the fact that the transcallosum responses occurred mainly as a result of the direct irritation of the callosum fibers by stimulating electrodes and entirely reflected the post-synaptic potentials.


[Effect of enteric oxygen therapy on the functional state of the liver in acute dystrophy]. Enteral oxygenotherapy influence was studied on rats with acute liver dystrophy caused by CCl4. Intragastric introduction of oxygen foam dicreased the intoxication and promoted a more rapid and complete restoration of the bile secretion intensity, the synthesis of primary biliary acids and their conjugation with amino acids, and also improved bile stabilizing properties.


[Mechanism of the hypercoagulation effect of hyperoxia]. It was shown in man and rabbits that a 30-minute inhalation of a 100% O2 under normal atmospheric pressure was accompanied by an elevation of the blood coagulation capacity and a sharp reduction of the count of platelets with the change of their structure. The trigger mechanism of the described hypercoagulation effect is possibly the viscous metamorphosis of platelets developing under the effect of oxygen activation of Hageman's factor.


[Block of presynaptic inhibition of spinal cord reflexes by ammonium acetate]. In experiments on cats ammonium acetate (AA) injected intravenously (2--4 mM/kg body weight) depressed the process of primary afferent depolarization (PAD) which were thought to be responsible for presynaptic inhibition of spinal reflexes. PAD depression is reversible and proceeds in parallel to depression of postsynaptic inhibition of monosynaptic reflexes. The ammonium depression of PAD is not connected with the block of the negative postsynaptic potential recorded from the dorsal surface of the spinal cord or with the block of the reflex electrical discharges from the ventral roots. A conclusion was drawn that one of the possible mechanisms for convulsive action of AA consists in depression of presynaptic inhibition. It is supposed that the depression of PAD by AA results from the block of the chloride ion pump existing in primary afferent terminals. The block of the pump leads to abolition of the EMF for the outwardly directed transmembrane chloride current producing PAD.


[Distribution of gamma-hydroxybutyric acid in different portions of the brain and in the serum of rats during anesthesia]. Dynamics of gamma-hydroxybutyric acid (GHBA) accumulation in different parts of the rat brain (the thalamus, hypothalamus, cerebellum, corpus striatum, cerebral hemispheres, medulla oblongata, corpora duadrigemina) and in the serum was studied by the improved gas-chromatographic method after intraperitoneal injection of gamma sodium oxybutyrate (1.5 g/kg). The GHBA content failed to differ much in the brain parts under study at the beginning of anesthesia, during and after it, only a somewhat higher GHBA content was seen at all the periods of anesthesia in the cerebral hemisphere, cerebellum, and corpus striatum. The GHBA level was constantly higher (especially at the initial period of anesthesia in the serum, then in the brain tissue.


[Effect of furosemide on the transport of organic substances in the kidneys]. The influence of furosemide on the maximal glucose reabsorption, cardiotrast secretion and urate excretion was studied in chronic experiment. Single injection of furosemide increased the maximal glucose reabsorption in dogs. Thesere was no alteration in the secretory cardiotrast transport in response to the drug administration. Furosemide administration produced an uricosuric action in dogs and rats.


[Effect of thymus extract and late thymectomy on interferon generation]. No production of interferon was observed in ten-day mice in response to the injection of the Newcastle disease virus. Single injection of the calf thymus extract fraction obtained by the method of Gujlling et al. to newborn mice induced the capacity of interferon genesis in the animals at the age of ten days. Adult rats produced interferon in response to Newcastle disease virus. The intensity of interferon synthesis was unaltered 2 to 3 months after thymectomy.


[Inhibition of passive cutaneous anaphylaxis by dipeptides]. The action of some dipeptides (Lalpha-alanyl-histidine, Lbeta-alanyl-histidine, histidyl-leicine and glycyl-histidine), and histidine on passive cutaneous anaphylaxis of guinea pigs was studied. Lbeta-alanyl-histidine (karnosine) and Lalpha-alanyl-histidine proved to inhibit the passive cutaneous anaphylaxis. Histidyl-leicine, glycyl-histidine, and histidine failed to produce any inhibitory effect on passive cutaneous anaphylaxis.


[Influence of the nervous system on the process of transplantation regeneration of skeletal muscle]. Completely excised Testudo horsfieldi gastrocnemius muscles were regrafted to the same site both with the nerve brought in contact with the graft and under denervation. The restoration of contractility and innervation of the grafts from the contacting nerve started one month after the operation and had not been completed 6 months after the operation. The grafts had a muscular structure type only after the restoration of innervation; otherwise, the connective tissue developed in the grafts. Two months after the operation a significant difference in the weight of the innervated and denervated grafts was recorded. With regard to restoration of innervation and graft weight indices, T. horsfieldi proved to be intermediate between the previously examined rat and frog.


[Implantation growth of nephrogenic tissue and the epithelium of renal nephron tubules in cultures within the body]. Comparative study of the implantation growth of nephrogenic tissue in a 17-day-old embryo of rats and the epithelium of nephrons in the one-month-old animals showed that nephrogenic tissue in the implants manifested regularities characteristic of its histogenesis. The nephron epithelium of the one-month-old animals is characterized by tissue growth and formation of atypical organ structures, this indicating its capacity for tissue and organotypical differentiation. A conclusion was drawn on wide range of the reactive and plastic properties of a nephron epithelium, as well as on the existence of its organotypical differentiation.


[Morphofunctional changes in the immune system during reparative regeneration of the liver]. A rise of the functional activity of the immune system was noted during reparative processes in the liver Resection of the liver was accompanied by sharp changes in the thymus and spleen structure. The thymus-dependent parts of the spleen were particularly reactive. Resection of the liver in rats was accompanied by an elevation in the bone marrow of the stem cell count (determined by the splenic colony method). The number of the colony-forming cells was significantly greater in the spleen of the recipients of lymphoid cells taken from the operated animals than in the spleen of the recipients of lymphoid cells from intact rats. In screening the limb the capacity to form endogenous colonies proved to be greater in partially hepatectomized rats as compared to the unoperated animals. In rabbits resection of the liver was accompanied by a significant increase of the immunological reactivity on the 1st-3rd postoperative days. Leukergia and leukocytolysis reaction displayed a marked intensification at this period.


[Morphofunctional reaction of the cortical lamina of the adrenal gland to reparative osteogenesis and administration of thyrocalcitonin]. A complex of morphofunctional changes of the adrenal cortex was studied on 150 albino male rats in case of thyrocalcitonin (TCT) administration and experimental fracture. There proved to be an increase of functional activity of the gland under conditions of reparative osteogenesis. The state of hyperfunction developed the first five days of TCT administration in a dose of 5 Units daily. The following saturation of the organism with TCT caused depression of the adrenal gland, particularly of its glucocorticoid function. It is supposed that the inhibitory effect of TCT on the adrenal cortex served as one of the mechanisms accelerating the repair processes in the bone tissue.


[Effect of repeated partial hepatectomy on cell division in regenerating rat liver]. The repeated partial hepatectomy (PH) on day after a 70% PH induced the following effect on the passage of rat regenerating hepatocytes through the mitotic cycle: it delayed (for about 2 hours) the cells in the G2-period, it almost failed to change the duration of the S period and delayed (by 6 to 8 hours) the cells in the G1-period. The sham repeated operation induced an analogous effect. This indicated that the action of repeated PH on the mitotic cycle of regenerating hepatocytes was determined by the operation stress factor. An additional stimulation of division by the repeated PH influenced the regenerative process as a whole.


[Quantitative distribution of satellite associations differing according to the number of chromosomes in human lymphocytes]. Statistical analysis of quantitative distribution of associations formed by 2, 3, 4, 5 and 6 acrocentrics (associations with a different numerical composition) revealed a good concordance of the empirical frequencies with the theretical ones calculated by the exponential distribution law with the basis of two. A good concordance in all the donors studied pointed to the strict regularity of the quantitative distribution of associations with a different number of acrocentrics and their special significance in human lymphocytes.


[Differences in the ultrastructure of the subunits of compact and diffuse chromatin]. The ultrastructure of subunits of the compact and diffuse chromatin of isolated Wistar rat hepatocytes nuclei was studied. The complexity of the chromatin subunits composed of the centrally situated nucleosome and of its capsule was confirmed. It was found that the capsule could exist in either compact or diffuse form, thus determining whether the chromatin was compact or diffuse. The capsule of the nucleosome in its diffuse form was supposed to represent the site of transcription.


[Development of the accessory apparatus of the chemosensitive structures of the rat tongue during ontogenesis according to scanning electron microscope findings]. The changes in the formation of pores of the taste bulb on the rat tongue was investigated by scanning electron microscopy. The heterochronic maturation of the lingual chemosensory auxiliary apparatus at different periods of postnatal ontogenesis was shown. The pores first appeared in the papilli localized on the radix and the dorsum of the tongue and later along the lateral lingual surface.


[New findings with regard to the fine structural organization of the subsynaptic zone of nerve cells]. Fine structure of the neurone subsynaptic area was studied by electron microscopy. Special cell organellae - microtubules - were found to be in close association with this neurone postsynpatic region. Dilating in the form of a funnel, their peripheral ends closely adhered to the post-synaptic membrane and as if coalesce with its internal osmiophilic layer. These observations definitely showed that there were direct structurally organized connections between the neurone synaptic area and the inner parts of the nerve cell cytoplasm. Functional importance of these connections is discussed.


[Electrical activity of the myocardium during work and at rest under hyperbaric conditions of many days duration]. Electrical activity of the myocardium in divers at rest and during physical work of various intensity under normal pressure and during one-week stay of these divers under the pressure of 5 absolute atmospheres (aatm) of N2O2. At rest and during the work of the same intensity the frequency of cardiac contractions under hyperbaric conditions was less than at 1 aatm. However, an increase in cardiac contractions during work was greater than at 1 aatm. During the work under increased pressure elevation of P wave of the ECG was more pronounced; this was possibly associated with the increased resistance in the pulmonary circulation in hyperbaria. There was noted reduction of the T wave amplitude and depression of the ST interval. Some divers displayed signs of aggravation of metabolic processes in the myocardium, disturbances of automation and conductivity.


[Changes in the electrogenic properties of striated muscle fibers during experimental botulism]. Changes in the electrical parameters of fibers of fast and slow muscles of rats during development of local botulism were studied. At the early stage of intoxication a decrease of the membrane potential of the fast and slow muscle fibers was found. At the stage of intoxication, alongside with an expressed membrane depolarization, there was a change of the input resistance, of the membrane electrical time constant, the threshold currents and the amplitude of action potentials, caused by direct intra-cell stimulation. Changes in the electrical parameters are more expressed in the fibers of the fast muscle.


[Myocardial resistance to adrenaline in rats adapted to hypoxia]. Expression of the damaging effect of adrenalin on the myocardium of rats adapted to hypoxia was studied under condition of adrenalin being injected into the integral body or in perfusion of an isolated heart. The damage was tested by the histoenzymatic reaction for the succinic dehydrogenase activity and staining for lipids. When the cardiotoxic dose (2.0 mg/kg) of adrenalin was injected intramuscularly to the adapted rats no damage of the myocardium was found, but perfusion of the isolated heart with adrenalin (20 microgram/ml) induced cardiocyte micronecrosis. The volume of these necroses was statistically less than in the isolated heart of the intact rats under analogous treatment. The difference between the sensitivity of the myocardium in vivo and in vitro indicated that in rats adapted to hypoxia the phenomenon of the myocardium protection from the damaging effect of adrenalin acted on the integral body level. An increased resistance of the myocardium proper seems to be caused by the increase of the metabolic system force during adaptation.


[Changes in the bioelectrical activity of pacemaker cells of the desympathized and reserpinized frog heart under conditions of parasympathetic rhythm acceleration]. A study was made of the mechanism of parasympathetic acceleration on Rana temporaria hearts with the preliminarily exhausted catecholamine stores due to desympathization and reserpinization of the animals. Bioelectrical activity of the cells of the isolated pace-maker was recorded. Parasympathetic acceleration was accompanied by an increase in the rate of accretion of slow diastolic depolarization (this indicating an active mechanism of this acceleration), and also a slight hyperpolarization and a decrease of the action potential duration. The acceleration effect and the changes of the form of the action potential were absent after atropine treatment of the preparation, this confirming the cholinergic nature of the parasympathetic acceleration. It is supposed that the parasympathetic system mediator acetylcholine--could decrease potassium or increase sodium permeability of the Pacemaker cell membrane, this leading to increase of the slow diastolic depolarization rate and to discharge acceleration.


[Restoration of the vital functions of animals resuscitated with the help of a donor following prolonged circulatory arrest]. Experiments were carried out on anesthetized dogs which had sustained a 15--20-minute circulatory arrest and were reanimated with the aid of donor circulation. In the I group of experiments the blood flow from the donor was directed to the heart of the revived dog, and in the II group--to the heart and the brain. Unlike other methods, donor reanimation, especially in the II variant of experiments, promoted a more rapid recovery of the vital functions of the organism and increased the number of survived animals. In spite of a complete apparent recovery of dogs after a prolonged circulatory arrest there were different changes in their brain depending both upon the duration of clinical death and the reanimation methods.


[State of microcirculation following massive administration of homologous donor blood to dogs]. Homologous normovolemic donor blood exchange provoked a moderate slowing down of the blood flow in the microcirculation and intravascular aggregation of the red blood cells--moderate or severe. Acute phenomena of blood deposition in the mesenteric vessels with a simultaneous reduction of the perfusion level in the microvessels of the bulbar conjunctiva developed in 25% of cases. Acute microcirculatory disturbances were transitory in character.


[Participation of individual brain regions in the development of acute prolapse of the brain]. Acute experiments were conducted on cats; the stereotaxis method was applied to search for morphological formations whose stimulation led to acute brain prolabination. This effect resulted from stimulation of the area hypothalamic lateralis, zona incerta, zonae H1 and H2, parafascicular, interstitial, and interpeduncular nuclei, and nucleus Darkschevitch. Against the background of the histological picture of acute prolabination, signs of brain edema and swelling were revealed in stimulation of the area hypothalamica lateralis, zone incerta, zonae H1 and H2.


[Influence of cation dyes on blood coagulation]. Experiments on rabbits showed that intravenous injection of dyestuffs of the thionine series (toluidine blue, azur A, 1:9 dimethylene blue) was accompanied by hypofibrinogenemia, a decrease in the concentration of prothrombin complex factors, thrombocytopenia and the lowering of the blood platelets adhesion against the background of delayed blood thrombogenesis. The blood heparin tolerance and the amount of free heparin were sharply lowered. The authors consider that the hypocoagulative effect of cationic dyestuffs on the blood was caused by the thrombocytopenia and by the lowering of the platelet aggregation activity.


[Antithromin activity following blockade of the reticuloendothelial system, splenectomy and partial removal of the liver]. The level of antithrombins II, III and IV decreased in proportion to the extent of intervention in destruction or removal of a part of the liver in rats. Destruction of the spleen led to depression, and removal--to activation of antithrombin IV. Back of the reticuloendothelial system caused a lesser fall of the antithrombin level than partial hepatectomy. The spleen is supposed to produce antithrombin IV inhibitor.


[Prevention of acute pulmonary edema in irradiated organisms]. Experiments were conducted on 212 albino rats. Preparations giving a marked prophylactic effect in the progress of the lung edema in the nonirradiated animals failed to influence the course of edema and even aggravated it in some of irradiated (650 R) animals. On the contrary, preparations ineffective or negatively influencing the nonirradiated animals were capable of causing a marked prophylactic effect in the irradiated animals. Consequently, the antiedema preventive measures in the irradiated and nonirradiated organisms should be different.


[Thermal effect of interaction of ATP with flaccid and contracted glycerinized fibers]. Heat accompanying the interaction between relaxed and contracted glycerinized fiber bundles of the striated muscles of rats and ATP was measured. Investigation of  the interaction concerned both relaxed and preliminarily contracted bundles. As apparent from the thermokinetic curves, the interaction of ATP with the noncontracted bundles yields a peak of the thermal potency which coincides in time with the contraction process; no such effect was produced in case of preliminarily contracted fibers. The authors conclude that a direct interrelationship exists between the rate of ATPase activity and the conformation of actomyosin system.


[Characteristics of the lactate dehydrogenase isoenzyme spectrum of the skin in the presence of thermal lesions]. Experiments were conducted on rats; a study was made of the activity of lactic dehydrogenase (LDH) and its isoenzymes in the zone of affection and in the adjacent areas of the skin at various periods after the burn infliction; on the 1st--8th day there occurred a reduction of the sum total LDH activity in the scab zone and the underlying tissue by 70--80%, and in the margin and the intact skin--by 50%. These changes were accompanied by shifts in the isoenzymatic LDH spectrum in the affected tissue; the activity of fraction 5 displayed a sharp rise on the 1st day and that of fractions 2 and 3--a reduction, on the contrary, by the 8th day there was seen some diminution of fraction 5 activity and an elevation of fractions 2 and 3 activity. The following picture is observed on the 14th--22nd day after the burn; the sum total LDH activity remains low, the isoenzymatic LDH spectrum in the margin and the scab is largely normalized, whereas in the underlying tissue there persist changes in the LDH enzyme ratio (a reduction of fractions 1--3 activity, and a rise of fraction 5 activity).


[Guinea pig brain and spinal cord phospholipids and cholesterol in tricresyl phosphate poisoning]. Chronic intoxication of guinea pigs was induced by intracutaneous inoculation of tricresylphosphate (TCP). The brain stem and spinal cord total phospholipids and total, free and esterified cholesterol were determined during the severe neuroparalytic stage of TCP intoxication. The content of phosphilipids and of total cholesterol was not altered, but cholesterol esters appeared to accumulate both in the brain stem and the spinal cord. Cholesterol esters are characteristic products of degraded myelin sheaths.


[Serotonin binding activity of light and heavy synaptosomes from different animal brain structures following light deprivation]. The extent of interaction between serotonin (ST) with light and heavy synaptosomes from different brain regions of normal and dark-reared rabbits was studied by the author's technique, using gel filtration. The activity of this interaction in the heavy synaptosomes of the visual cortex and the colliculi superiores of the control rabbits was the same and significantly higher than that in the motor cortex. The light synaptosomes of all the investigated regions were similar by the extent of this process activity. In dark-reared rabbits the activity of ST binding by heavy synaptosomes in the visual cortex and the colliculi superiores decreased by 74--81 per cent only. A fall in the ST binding by light synaptosomes in all the regions was the same (approximately 73 per cent as compared to the control). The results obtained are discussed in the light of a possible mediator or modulator role of ST in the visual system structures.


[Vectorgraphic assessment of the influence of different psychic stimulators on the avoidance behavior of rats]. The authors assessed the influence of psychostimulants on relearning of rats of the avoidance direction in a Y-maze. The effects were analyzed vectorographically with the absolute and relative values by the main response indices. The behaviour curve of the group of animals was drawn in both cases. Sydnocarb (20 mg/kg) produced the most optimal effect; in difference from caffeine (25 mg/kg) and d,1-amphetamine (0.5 mg/kg) it not only stimulated the active avoidance, but also improved the animal relearning. An increase of the sydnocarb dose to 50 mg/kg failed to disturb rat behaviour, whereas caffeine (50 mg/kg), and particularly d, 1-amphetamine (5 mg/kg) did cause such disturbance. The behaviour curve of the latter coursed beyond the level of the initial level and was characterized by a marked aggravation of passive avoidance.


[Effect of phentolamine on cerebral circulation]. The influence of phentolamine hydrochloride on the volumentric circulation rate of the cerebral blood flow, the tone of the cerebral vessels and oxygen tension in the cerebral tissue was studied in acute experiments on anesthetized and nonanesthetized cats. Injected intravenously, phentolamine hydrochloride was found to lower the intra- and extracranial  vessels for a long time, the latter to a greater extent. The circulation rate of the cerebral blood flow decreased under conditions of a significant hypotension caused by phentolamine hydrochloride and increased with a stable perfused pressure; pO2 changes in the cerebral tissue corresponded mostly to the blood flow. Preliminary atropinization of the animals and denervation of the carotid regions failed to influence the effect of phentolamine hydrochloride. The latter decreased or prevented the vasoconstrictor action of norepinephrine and phenylephrine hydrochloride (mesatone) on the cerebral vessels.


[Correlation between the antiarrhythmic activity of acyl derivatives of phenothiazine and their affinity for phospholipid membranes]. The interaction of thirteen antiarrhythmic active phenothiazine 10-acylaminopropionil derivatives with artificial phospholipid membranes was studied. Blinding constant (K) of this interaction was determined by means of a fluorescent probe. There was found a valid correlation between K and antiarrhythmic activity (A) for 10 substances; the greater the K--the greater the A. Three substances characterized by the greatest K had, however, a low A. It can be assumed that the interaction of antiarrhythmic drugs with phospholipids of target membranes in vivo is an important element of the molecular mechanism of action. At the same time a very high affinity to lipids can possibly cause a delocalization of the drug in the organism and a decrease of its antiarrhythmic activity.


[Possible pharmacologic regulation of the motor activity of the gastrointestinal tract]. The authors present the results of pharmacological study of the effects of gallic salt cynoglossofin-geliosupin alkaloid (cyngal), isolated from the Cynoglossum officinale, on the gastrointestinal motor activity. A high stimulating activity of this preparation both in acute and chronic experiments on dogs was shown by using the balloon and electrographic recording technique. The ability of cyngal to release serotonin from the bound state can account for the gastrointestinal motor function stimulation.


[Mechanism of the lipid mobilizing effect of etimizol]. The influence of ethymizol on the mobilization of free fatty acids and the role of hormones of the pituitary-adrenal system in the lipolytic effect of this drug was studied in experiments on rats. The lipomobilizing effect of ethymizol was clearly expressed in the intact, hypophysectomized and adrenalectomized rats. The effect of the drug disappears in rats with a simultaneous extirpation of the pituitary and the adrenal glands, but it again manifests itself after hydrocortisone injection to these animals. A conclusion on the presence of direct ethymizol action on the mobilization of fatty acids and on the permissive role of corticosteroids in lipid mobilization effect of ethymizol was made.


[Suppression of hypersensitivity of the delayed and immediate types in guinea pigs by methylene diphosphonic acid]. The effect of methylene diphosphonic acid subcutaneous injection on delayed, as well as on the immediate hypersensitivity in guinea pigs was studied. It was shown that methylene diphosphonic acid (30 microgram/g) inhibited the delayed and immediate hypersensitivity by 60--80%, as compared to control animals.


[Suppression of the anaphylactic response of isolated smooth muscle organs by potassium arsenite]. A possibility of inhibition of the anaphylactic reaction of the isolated human smooth muscle and smooth muscle of guinea pigs by inorganic arsenic was studied. Liquor kalii arsenicosi (Fowler's solution) completely blocked the development of anaphylactic bronchospasm and anaphylactic release of the pharmacologically active substances from the guinea pig lungs.


[DNA synthesis by granulation tissue fibroblasts under conditions of stimulation of the wound process]. The changes in the DNA synthesis in the granulation  tissue fibroblasts in the wounds of adult animals given potassium orotate and in controls were studied. For this purpose a daily autoradiographic examination of the wound areas were conducted in the both groups of animals. It appeared that under the effect of potassium orotate (0.2 ml of 2% solution) there was more frequent involvement of fibroblasts  into  the DNA synthesis; under conditions of the wound process stimulation there occurred an increase of the proliferative activity of these cells.


[Influence of physiologically active substances isolated from the thymus on the course of the wound process following cryodestruction in rats]. Experiments were conducted on 40 male albino rats subjected to general irradiation in a dose of 200 R, to study the influence of "thymarin"--a compound obtained from the thymus of cattle (representing a complex of three physiologically active polypeptide fractions with an average mol wt 10 000) on the course of local wound process after cryodestruction of the hard palate mucosa. The preparation was injected subcutaneously for ten  days after cryodestruction. The experimental data obtained pointed to a favourable influence of "thymarin" on the course of regenerative processes, as shown by accelerated rejection of necrotic tissues, more rapid epithelialization of wound surface, and prevention of secondary infection.


[Character and frequency of pathologic changes in the single kidney of rats following removal of the other in old age]. Unilateral nephrectomy was performed in male rats weighing 500--850 g; the remaining kidney underwent compensatory hypertrophy which in rats weighing 700--850 g proved to be higher in 1 to 2 months than in the animals weighing 500--600 g (hypertrophy index--70--92 and 56--58%, respectively). Histological examination demonstrated that such a marked hypertrophy of the single kidney in senile rats was not the result of its sickness, since pathological changes, sometimes encountered in the intact and hypertrophied kidneys were revealed in 38 of 223 animals. The data obtained permit to suppose that the compensatory -restorative capacity of the kidneys fails to diminish in senile animals.


[Mycoplasma hominis as an agent of respiratory tract diseases]. Respiratory organs of newborn rats inoculated intranasally with broth culture of Myc. hominis were studied by the histological, histochemical and immunofluorescence methods. Tracheitis and development of purulent and interstitial pneumonia with a hemorrhagic component were revealed 24 hours after the infection. These changes were observed up to the 7th day of the experiment. At the same period a specific fluorescence of the Myc. hominis antigen was found by the antibody fluorescent test. The present study pointed to the pathogenicity of the Myc. hominis for the respiratory tract of the newborn rats.


[New model of dynamic work in small laboratory animalsu]. A new method of compelling rats and mice to perform uninterrupted dynamic work has been devised. The animal, fixed from its tail and situated in vertical position in respect to the surface of the water with which it comes in contact only with its muzzle and forepaws, is compelled to execute uninterrupted muscular work. Total exhaustion is determined by the cessation of muscular activity, as a result of which the animal, choked by water, perishes. The method is suitable for carrying out the screening of pompounds having adaptogenic properties, for studying the mechanism of raising the endurance; it also allows registration of  physiological parameters in the course of the experiment.


[Improvement in the histochemical method of detecting open capillaries]. A modification of Pickworth's method for detection of open capillaries is described. The special feature of this method consists in freezing the organ in situ with liquid propane, cooled with liquid nitrogen, with the subsequent lyophilization of the preparation and its fixing in gazeous formaldehyde. The slides were stained strictly according to Pickworth.


[Microthermal method of separating red cells into groups according to age]. The microthermal method of red blood cells' division according to their age is based on the formation of a temperature gradient with the aid of microthermoresistor. The red blood cells of different age fractions are consecutively localized and selected in the zone of microthermoresistor. They differ from one another according to their biochemical indices. The microthermal method of erythrocytes' division offers a possibility of differential studying the blood cells.


Differential responses to transmural stimulation and vasopressin in isolated strips of artery and vein of human mesoappendix. Responses to exogenous norepinephrine (NE), transmural electrical stimulation, 5-hydroxytryptamine (5-HT) and lysine vasopressin were studied in isolated helical strips of the small artery and vein from the mesoappendix of patients undergoing incidental appendectomy at the time of cholecystectomy. Responses to NE and 5-HT were similar in each vessel. Arterial strips were unresponsive to electrical stimulation and responses to vasopressin were greater than those to NE in this tissue. Venous strips were unresponsive to vasopressin. Relaxation of exogenous NE responses following oil immersion of arterial strips was unaffected by cocaine whereas relaxation of similarly treated venous strips was markedly prolonged. The data suggest: (1) that the artery of human mesoappendix is poorly innervated and (2) that vasopressin is clearly more active on human mesoappendix artery than it is on human mexoappendix vein. The latter observation may help to explain the efficacy of vasopressin infusion in gastrointestinal hemorrhage secondary to portal hypertension.


[Penicillin-induced immunhaemolytic anaemia. In vitro studies using separated monocytes (author's transl)]. Under certain conditions human monocytes were able to bind and ingest red cell-antibody complexes in vitro. Using penicillincoated red cells and purified monocytes we investigated sera of patients with penicillin allergy. It was shown that sera containing IgG-antibodies against penicillin induced the binding of penicillin-coated red cells to isolated monocytes provided IgG-antibodies of high titer were present. Inhibition and absorption tests demonstrated the specificity of the reaction in terms of IgG-antibodies and the drug. Monocyte binding was also studied in respect to the cross reactivity of penicillin antibodies and cephalosporins. We concluded that antipenicillin-antibodies of the IgG-class were able to induce an immunphagocytosis in vitro, if the drug was present in the test system. The reaction was dependent on the amount of antibodies of the IgG-class.


Glucosephosphate isomerase deficiency type Liège: a new variant with congenital nonspherocytic hemolytic anemia. GPI deficiency was detected in a three year old girl of Morrocan origin suffering, since birth, from hemolytic anemia. The defective GPI is very thermolabile and migrates on starch gel electrophoresis as a single band with a mobility of 96% of the normal main band. The purification of the patient's GPI resulted in a 16000-fold enriched preparation, free of any other enzyme activity. The yield was 35%. The purified enzyme was very unstable even at low temperature. The kinetic constants of the forward and backward reaction as well as the inhibitory constants of 2,3-DPG and 6-PG do not significantly differ from normal values. The biochemical properties of the patient's GPI indicate a new variant designated type Liége.


Cryopreservation of blood mononuclear leukocytes and stem cells suspended in a large fluid volume. A preclinical model for a blood stem cell bank. It was the purpose of this study to establish and evaluate a freezing-and-thawing method for preservation of hemopoietic stem cells from the peripheral blood. Blood leukocytes collected by means of an IBM Blood-Cell-Separator were frozen in plastic bags using 10% DMSO and controlled cooling rates. Thawing was performed rapidly, and DMSO was diluted and removed prior to the in-vitro and in-vivo assays. The mean recovery of mononuclear cells collected from 82 leukaphereses was 86%. To assess the recovery of cryopreserved hemopoietic stem cells, the soft agar culture method adapted for the dog was used. There was no significant difference in the CFUc recovery per 1 X 10(6) mononuclear cells or in per leukapheresis after different cryopreservation times (1--6 and 7--27 months). To evaluate the hemopoietic repopulation capability of cryopreserved blood stem cells, leukapheresis-derived leukocytes were transfused into 1200 R whole body x-irradiated dogs. The hemopoietic repopulation pattern at day 10 after transfusion of comparable numbers of fresh or frozen leukocytes was not significantly different, as measured in bone marrow smears and sections and by granulocyte concentration in the peripheral blood.


Comparative haematological changes after 15 mev neutron- and X-irradiation. I. Differentiation counts in peripheral blood and bone marrow. The effect of 15 MeV fast neutrons on blood and marrow cells of young NMRI-mice was compared to that of X-rays after single doses of whole-body irradiation. Using differential cell counts in peripheral blood and bone marrow smears, quantitative data are presented. Complete recovery of peripheral blood and bone marrow cells to control values was not observed. Lymphocytic regeneration was particularly retarded. Irradiation with fast neutrons affected the regneration of marrow cells more severely than with X-rays.


[A simple filtration technique for the observation of the deformation of human erythrocytes during pregnancy (author's transl)]. A simple rheological test method, as developed by Reid and Dormandy, was applied. In a group of pregnant women (n = 25) without pathological conditions the filtrability of whole blood and of a 10% erythrocyte suspension was determined. The control is a group of healthy nonpregnant patients (n = 7) at different times of the ovulatory cycle. Compared with the control group the flow rate of whole blood in the pregnant state is decreased about 30%, whereas that of the erythrocyte suspension about 40%.


Human lymphocyte culture: intrinsic factors influencing the quality of chromosome preparations. In a cytogenetic study of the consecutive cell cycles (M1, M2 etc.) from human lymphocyte cultures after 5-bromodeoxyuridine incorporation followed by differential Giemsa staining, the metaphases of M2 and subsequent in vitro divisions have been found to spread better than those of M1 cells, as if the cells of in vitro generation suffer some membrane alterations. Moreover presence of S or G2 phase, leukocytes in a blood sample may result into early proliferation in a PHA stimulated culture system, so that the metaphase yield at 72 h will be larger than otherwise, a sizeable portion of which, being in M2 or subsequent cell cycles, will spread better. Thus such individual or transient intrinsic factors of haematologic state may influence the success of a leukocyte culture and the quality of chromosome preparation.


[Coagulation factors in human born blisters (author's transl)]. Following clotting factor assays were performed on the fluid of burn blisters of 11 patients with severe burns: Fibrinogen levels, Factor II, V, X and XIII, thrombin time, fibrin split products, plasminogen, antithrombin III, IgA, IgM, IgG, ethanol gelation test and total proteins. The results showed, that a quantity of Factor II, X and XIII, antithrombin III, plasminogen and IgG had left the circulation. On the contrary we found only small concentrations of Factor V, fibrinogen, IgM and IgA in the fluid of burn blisters. This distribution suggested that the losses of plasma proteins into the burn blisters were correlated to their concentration and their molecular weight. The decrease of plasma coagulation proteins during the first days after severe burns was probably partly due to losses through the walls of the vessels, because of the increased capillary permeability.


Apparent "inhibition" as tested by means of the dilution curve system in patients with clotting defect due to liver damage. At equivalent Thrombotest basal values on undiluted non-contacted plasma, there is no difference between coumarin plasma and liver damage plasma in the dilution curve system. A hemophilia BM plasma with longer basal clotting times yielded a much flatter curve and a very large "inhibitory" effect (greater than 6 Units). A coumarin plasma with the same basal Thrombotest clotting times as Hemophilia BM plasma, namely 100 seconds, yielded a much steeper curve and a very low inhibition (0.7 Units). These findings are against the presence of inhibitors in coumarin or liver damage plasmas.


[Electronic platelet counting with particular reference to thrombocytopenias (author's transl)]. Platelet counts in platelet-rich plasma without hematocrit dependent correction were performed by following rapid and simple steps: 1. pre-dilution of 20 microliter of whole blood by an isotonic solution 1:25; 2. stabilized low-speed centrifugation with 55 g for 5 minutes; 3. final dilution 1 : 5000; 4. enumeration by use of a TOA platelet counter PL-100 which has been technically improved in comparison to similar machines. Erroneously high results were obtained after a too short or too low centrifugation. As reason for this artifical small pulses due to disturbances of the flow patterns around the aperture (so-called vortex-effect) can be assumed having been caused by large-volumed erythrocytes and leukocytes in the suspension. The routinely used procedure was reliable for all platelet ranges, especially in thrombocytopenias between 100 X 10(9)/l and 25 X 10(9)l. In lower ranges comparisons with visual counts are essential.


[Aetiology of the thrombocytopenia in vinylchloride disease (author's transl)]. Thrombocytopenia is often one of the first signs of vinylchloride disease. Morphological investigations showed that it is caused by splenic alterations. Besides splenomegaly, there are significant structural changes in the red pulp cords affecting the microcirculation. These quantitative and qualitative alterations cause increased platelet pooling and and increased destruction of platelets, which result in a decrease in thrombocytes in the peripheral blood.


Chronic superficial dermatitis and poikiloderma. The terms chronic superficial dermatitis and poikiloderma have in the past both been called parapsoriasis en plaques although they are entirely different disorders. Chronic superficial dermatitis is benign and does not advance to a reticulosis. Poikiloderma of the prereticulate type, on the other hand, may progress and may be the cause of death in some cases. It should no longer be considered a separate entity but should be regarded as part of the spectrum of mycosis fungoides.


Evaluation and staging in the Scottish Dermatological Society mycosis fungoides register. The patients registered in the first two years of the Scottish Dermatological Society's Malignant Lymphoid Neoplasm Register are described. Criteria for inclusion in the Register and laboratory tests carried out in the staging of these patients is listed. Significant abnormalities detected to date include low levels of circulating E and EAC rosette forming cells and an elevated IgE level in a proportion of patients. It is hoped that continued monitoring of these patient will clarify the relationship of these abnormalities to the natural progression of the disease.


Scandinavian mycosis fungoides study group. A multicenter study group on Mycosis Fungoides in Denmark, Norway and Sweden has been active since 1974. Staging procedures based on a 5 stage-system have been established, and treatment protocols have been worked out. Topical nitrogen mustard with and without toleranceinduction has been applied on stage II, and Bleomycin has been randomized against Bleomycin and Methotrexate in stage, III, IV, and V. Protocols containings PUVA are now activated, with PUVA given in combination with Cyclophosphamide for extracutaneous forms of Mycosis Fungoides.


Whole cutaneous irradiation in mycosis fungoides with 55KV x-rays. Technical study. The authors describe a technique for a whole cutaneous superficial irradiation of mycosis fungoides by means of a fixed 55 KV X-Rays generator and a moving couche. Results of the dosimetric study are compared with thoses obtained with Lithium fluoride. Since 1964, twenty five patients have been treated. The results appear to be equivalent to those obtained with electrons. The technical problems of each methods are discussed.


The control of influenza.

The control of influenza. Influenza virus differs from the usual agents of epidemic disease by its extreme variability. Since consecutive outbreaks are caused by antigenically different viruses, both herd immunity and vaccination are largely ineffective and the epidemiology is characterized by pandemics, sensu stricto. Severe pandemics occur every 10-12 years, followed by a period (subtype era) over which the evolution of the virus follows a predictably regular course. This process can be imitated in the laboratory, yielding mutant viruses which may serve as prospective vaccines. The transition between subtypes is abrupt and hitherto unpredictable. There are indications, however, that the number of subtypes is limited and that they are linked in a secular cycle of about 70 years. If this proves to be correct, it should be possible to anticipate even the major antigenic shifts and thus eventually fully control the disease.


[Epidemiology and control of rabies].

[Epidemiology and control of rabies]. The epidemiological criteria of the present sylvatic rabies epizootic are shown using the situation in the Federal Republic of Germany and its neighbouring countries as an example. It is demonstrated that the fox plays the leading role in transmitting the disease to other animal species and remains the main vector in the epizootic. Mustelids are of secondary importance. Cervides, rodents and domestic animals are of no concern in the spread of rabies. Rabies control measures have to be aimed at the population reduction of but one species, the fox, since the frequency of rabies among this species is primarily dependent on the population density. Other wild carnivores especially badgers should be spared. Intensified shooting of foxes as a single control measure has proven ineffective. According to the results obtained in Central Europe, the gassing of fox dens, where applicable, has proven to be the best single measure regularly resulting in a decrease of rabies cases. In individual instances this has led to a complete extinction of rabies. The oral immunization of foxes is not yet regarded as acceptable; large-scale success with this method is not to be expected.


The significance and nature of defective interfering viruses. Deletions in viral genomes appear to be a common occurrence in the replication of all DNA and RNA viruses which have been adequately studied. Such defective genomes can replicate in the presence in the same cell of a helper virus as long as the deletion does not involve the initiation site for genome replication. Coinfection of a cell with defective and "normal" infectious virus leads to reduction in the yield of the latter. The nature of DI viruses and genomes found in Sindbis virus-infected vertebrate cells during "undiluted passage" series is discussed. This procedure leads to the accumulation of progressively shorter viral RNA genomes with internal deletions. The enrichment is limited to genome lengths which are integral fractions (1/2, 1/3, 1/4, etc.) of the complete genome, and these are also found in viral particles released at the corresponding passage levels. It is believed that the selective accumulation of these fragments is governed by constraints of assembly which demand that one full genome equivalent be packaged in a released particle. In contrast to vertebrate cells, cultured mosquito cells do not seem to produce or "recognize" DI particles. Possible implications for the epidemiology of arthropod-transmitted alphaviruses are presented.


[Genetically conditioned resistance against influenza viruses]. A strain of influenza A virus adapted to macrophages replicated and caused a cytopathic effect in macrophages from susceptible mice. Neither replication nor cell destruction occurred in macrophages from genetically resistant animals.


[Pathogenesis of equine infectious anemia (with reference to similar chronic viral infection)]. 1. Equine infectious anemia (EIA) is an immunologically-medicated disease. Immune complexes formed in blood and tissues are responsible for most symptoms and lesions (anemia, splenomegaly, lymphadenopathy, glomerulonephritis, etc.). In addition, a state of cellular hypersensitivity of the delayed type is involved in the pathogenesis. 2. Periodical attacks of pyrexia and clinical illness in the presence of immunity are caused by antigenically-modified variants of virus. By means of immunosuppressive treatments similar relapses of fever associated with the appearance of new virus variants can be also provoked during longlasting asymptomatic periods. 3. The mechanisms responsible for the lifelong persistence of virus are not fully elucidated. Obviously of prime importance is the viral antigenic drift allowing the virus to escape from humoral and cellular immune reaction. Finally, however, a state of cell-mediated immunity ensuring protection against homologous and heterologous virus strains may be reached. 4. Pathogenetic analogies and differences existing between EIA and other chronic viral infections of animals are recorded.


The cardiovascular response to dimaprit, a selective histamine H2-receptor agonist. 1 The cardiovascular responses to dimaprit (S-(3-dimethylaminopropyl) isothiourea) a selective histamine H2-receptor agonist have been studied in anaesthetized cats, dogs, rats and rabbits. 2 Dimaprit lowered systemic arterial blood pressure in all species whether given by intravenous injection or by continous infusion. Intra-arterial injections or infusions caused vasodilatation in the femoral vascular bed. 3 In the cat, continuous intravenous infusions of dimaprit lowered blood pressure without any significant change in heart rate or cardiac output. The fall in blood pressure was thus due to a decrease in peripheral vascular resistance. 4 Dimaprit, given intravenously, increased coronary and gastric blood flows and there were associated marked reductions in vascular resistance. Small reductions in vascular resistance occurred in skeletal muscle, in the intestine and the kidneys. 5 The histamine H2-receptor antagonists, metiamide and cimetidine, antagonized the depressor and vasodilator responses to dimaprit.


Effects of N-benzyl-L-valine on contractions of guinea-pig myometrium in vitro. A claim that N-benzylvaline is an exceedingly potent stimulant of guinea-pig myometrium has not been confirmed, but less potent stimulant or inhibitory effects were seen in a few experiments.


Interdependence of ion transport and the action of quabain in heart muscle. 1 The influence of ouabain (0.4 muM) on contractile force and cellular Na and K concentrations was investigated in isolated left atria of the guinea-pig at rest and at different beat frequencies. Simultaneously the binding of ouabain to the tissue was determined.2 Strict dependence of rates of onset of positive iontropic action and of binding of ouabain on beat frequency are limited to conditions where no alterations of cellular Na and K concentrations occur. A correlation was observed between sodium flux per unit time and the development of positive inotropism and binding to the receptors of ouabain.3 Ouabain exerts its positive inotropic effect without affecting the intracellular Na and K concentrations in spite of the fact that under these conditions even the majority of binding sites, i.e. Na-K-adenosine triphosphatases (Na-K-ATPases), are occupied by the drug. The positive inotropic effect may be explained by a ouabain-induced conformational alteration of the Na-K-ATPase which leads to structural alterations of the plasmalemma connected with an increased availability of coupling calcium.4 Increasing the frequency of stimulation over a critical value, which appears to be determined by an overloading of the Na pump, induces a decrease in contractile force, cellular accumulation of Na and loss of K, and eventually contracture.5 The rate of binding of ouabain appears to depend on the actual concentration of particular conformations of the Na-K-ATPase with high affinity for ouabain. These conformations transiently occur during a pumping cycle and their concentration may therefore be dependent on the frequency of cycling which in turn is determined by the frequency of contraction.6 Ouabain can easily be washed out from the tissue irrespective of the condition of the muscle. If, however, the intracellular Na and K homeostasis is impaired, the inhibition of the pump persists even if ouabain is released from the binding sites upon wash-out. It is suggested that the inhibition of the pump is maintained by an increased intracellular Ca ion concentration and a depletion of ATP.7 A kinetic model is proposed for the interaction between cardiac glycosides and the Na-K-ATPase in intact heart muscle cells.


The enhancement of chlorpromazine-induced hypothermia by lesions in the anterior hypothalamus. 1 Administration of chlorpromazine (Cpz), either systemically or centrally, to unanaesthetized rats at an environmental temperature of 23 degrees C caused dose-dependent hypothermia. 2 In order to achieve equivalent hypothermia, intraventricular administration required a total dose of 20 microgram Cpz and and intraperitoneal administration a dose of 9.7 mg/kg body weight. Accordingly, the dose-ratio between intraventricular and intraperitoneal administration was 1 to 110. Cpz apparently exerts its hypothermic effect by acting directly on central nervous structures rather than through peripheral sites. 3 Cpz-induced hypothermia was potentiated by preoptic anterior hypothalamic (POAH) lesions but not by lesions of the ventromedial nucleus (VMN) of the hypothalamus. It was found that Cpz induced hypothermia most readily in rats with large POAH lesions (-10.4 degrees C), less so in rats with spinal lesions (-5.5 degrees C) at least with control rats (-2.9 degrees C).


Do central dopamine receptors have a physiological role in thermoregulation? 1 Core and tail skin temperature was measured in rats which had guide cannulae implanted into their brains to allow drug injections directly into the preoptic anterior hypothalamus. 2 Apomorphine and dopamine (10 microgram in 1 microliter) injected into the area of the preoptic anterior hypothalamus caused a fall in core temperature which was preceded by a rise in tail skin temperature. 3 The decrease in core temperature following central injection of either apomorphine or dopamine was significantly reduced by pretreating rats for 2 h with pikozide 0.5 mg/kg i.p.). 4 Bilateral intrahypothalamic injection of pimozide (0.5 microgram in 1 microliter) significantly reduced the hypothermic effect of systemic apomorphine (1.25 mg/kg i.p.). 5 Control rats placed 65 cm below a 250 W infrared lamp responded with vasodilation of tail skin blood vessels as indicated by an increase in tail skin temperature. Pimozide pretreatment (0.5 mg/kg i.p.) significantly reduced this response. 6 These results suggest that the preoptic anterior hypothalamus contains dopamine receptors which mediate hypothermia in rodents and raise the possibility that endogenous dopamine has a physiological role in thermoregulation.


Inhibition by a stable analogue of adenosine triphosphate of platelet aggregation by adenosine diphosphate. 1 In citrated platelet-rich plasma, freshly prepared from rabbit blood, the velocity of platelet aggregation was within limits proportional to the log of the concentration of added adenosine diphosphate (ADP). 2 Addition of either adenosine triphosphate (ATP) or its beta,y-methylene analogue inhibited aggregation similarly except that the analogue was about half as potent as ATP. beta,y-Methylene ATP also reversed the optical effects associated with the shape change of platelets very similarly to ATP itself. 3 As beta,y-methylene ATP is not a substrate for nucleoside diphosphokinase, these observations do not support the proposition that inhibition of aggregation by added ATP is due to its utilization by the nucleoside diphosphokinase of platelets.


Hyperthermic effects of morphine: set point manipulation by a direct spinal action. U Rats were implanted with chronic indwelling catheters in the lumbar spinal subarachnoid space in order to study the effects of morphine on body temperature. 2 Morphine administered intrathecally produced a dose-dependent rise in body temperature that was antagonized by naloxone. 3 The rise in body temperature evoked by a given dose of morphine appeared to be independent of the environmental temperture ((4 degrees C to 32 degrees C) and was consistently associated with coordinated thermoregulatory responses (i.e. shivering and tail vasoconstriction). The fall in body temperature observed in these hyperthermic animals, following naloxone, was associated with a vasodilatation which coincided with the fall to the premorphine temperature level. 4 Morphine administered systemically also produced hyperthermia. This was only partially reversed by intrathecal naloxone. In animals made tolerant to the hyperthermic effects of systemic morphine, the intrathecal administration of naloxone produced a fall in body temperature. 5 Naloxone alone, administered either intrathecally or systemically, had no effect upon body temperature. 6 We suggest that morphine exerts a direct, pharmacologically specific effect on the spinal cord, which results in an altered thermoregulatory set point in the rat.


Comparative inhibitory effects of 3-quinuclidinyl benzilate (QNB) and atropine on amylase release from rat pancreas. 1 Secrection of amylase from rat pancreas stimualted by urecholine was studied in relation to its inhibition by atropine and 3-quinuclidinyl benzilate (QNB). 2 Urecholine-induced secretion was completely abolished by atropine at 10(-6)M and QNB at 10(-8)M. Significant inhibition could be detected at 10(-8)M atropine and 10(-10)M QNB. 3 The secretory response to pancreozymin was not blocked either by atropine or QNB. 4 The inhibitory effect of QNB remained for at least 90 min after its removal from the incubation medium. 5 It is concluded that QNB is 10 times more potent than atropine in inhibiting pancreatic amylase secretion induced by urecholine.


Assessing dangerousness in criminals.

Assessing dangerousness in criminals. This article formulates a definition of the term dangerousness, indicates why the commission of dangerous offences cannot be reliably predicted, and then reviews the several factors which have been or might be used by those who have to make decisions about dangerousness in criminals. Its suggests that these factors are useful insofar as they help to illuminate the individual's capacity to feel sympathy and to learn by experience. Since the accuracy of prediction varies inversely with time, the maintenance of personal relationships and good communication seems the inescapable requirement in the management of potentially dangerous criminals.


Writer's cramp--a rational approach to treatment? The history of writer's cramp is reviewed, and the study of ten cases described. Nine of the patients were male with obsessional personalities, and involved in a conflict with some bearing on the act of writing. Treatment by psychotherapy and re-education produced either temporary or little improvement; biofeedback, used in six cases, produced some benefit in four, of which only one relapsed. Although no statistical weight can be attached to the results of so short a series, biofeedback appears to offer a promise of response which merits further investigation. The use of the electromyograph is discussed also as a means of discriminating between tension and tremor in such cases, with particular reference to their psychosomatic meaning.


Psychiatric morbidity among university students in Egypt. During a nine-month period (1974-75), 1,050 students (846 male, 204 female) at Ain Shams University, Cairo, attended the Student Health Centre. Fifty-two per cent were referred there by their general practitioners, 5 per cent by their families and 3 per cent through their faculties; the remainder (41 per cent) were self-referred. Male patients represented 2-8 per cent of the male students, but female patients only 0-9 per cent of the female students. In faculties dealing with practical subjects the male-female ratio was higher than in those dealing with more theoretical subjects. The diagnoses included anxiety neurosis (36 per cent of the cases), schizophrenia (18 per cent), depression (15 per cent) and neurotic depression (12 per cent).


Hyperostosis frontalis interna and mental morbidity. Forty-six mentally ill women with radiologically verified hyperostosis frontalis interna (HFI) were compared with 46 matched mentally ill women without HFI in respect of mental morbidity among the full siblings of the two groups. It was found that mental morbidity was lower among the siblings on mentally ill women with HFI than among those of similar mentally ill women without HFI. A reasonable interpretation of these findings is that the combination mental illness-HFI is more often exogenously determined than other forms of mental illness.