Some properties of the small homodisperse RNAs in the cytoplasm of HeLa cells. Two homodisperse, methylated, small molecular weight RNAs, that have been previously described in HeLa cells and that are apparently coded by the nuclear genome, appear in the cytoplasm shortly after transcription and are detected in the cytoplasm with a half-life of a few minutes. Under the denaturing conditions of urea-polyacrylamide gel electrophoresis, the migration of these RNAs indicated nucleotide lengths around 190 (A) and 160 (B). Neither A nor B RNAs differed in their electrophoretic mobility when comparing samples from 10 to 120 min incubation with [3H]uridine. When the detergent-treated postmitochondrial fraction from cells incubated for 60 min with [3H]-uridine was centrifuged through a 0.3 M NaC1/0.5 M sucrose cushion, the resulting pellet showed a marked increase in the ratio of counts A/4 S RNA, and particularly B/4 S RNA, suggesting that these RNAs might not exist free in the cytoplasm. At low concentrations of camptothecin (1-2.5 mug/ml), the accumulation of A and B RNA was greatly suppressed, while the synthesis of 4 S and 5 S RNA was less affected. Their accumulation (particularly that of B RNA) was enhanced when cells were exposed to inhibitors of various steps of protein synthesis (puromycin, cycloheximide, pactamycin, emetine). Pulse-chase experiments with actinomycin D during suppression of protein synthesis indicated that, at least in the case of B RNA, this increased accumulation was due, at least partly, to a marked prolongation of its half-life.


Liver protein synthesis. Molecular weight distribution of pulse-labeled polypeptide chains in normal and thyroidectomized rats. Equations are presented for determination of elongation rate in vivo for a heterogenous population of polypeptide chain molecular weights. The distribution of pulse-labeled polypeptide chains in rat liver deoxycholate-soluble protein has been obtained by sodium dodecyl sulfate-gel electrophoresis and used to compute a theoretical curve for determination of synthesis time of a 50000 mol. wt. polypeptide chain (tc50). Values of tc50 for normal and thyro-parathyroidectomized Long-Evans male rats were 1.2 and 1.75 min, respectively, representing protein synthetic rates of about 7.5 and 5.1 mg protein/g liver/h. No difference in the molecular weight profile of liver polypeptide chains on the basis of labeling or Amido-black staining was observed between the two groups. The distributions of radioactivity before and after secretion of labeled plasma protein are compared. The role of protein-synthetic rate in the changing enzyme levels associated with thyroid hormone is discussed.


Protein synthesis initiation factors from chicken erythroblasts. Two factors (IF-I and IF-II) necessary for the initiation of protein synthesis have been partially purified from a 0.5 M KC1 wash of chicken erythroblast polysomes. IF-I mediates the binding of the initiator tRNA and GTP to a 40 S ribosomal subunit, resulting in the formation of a 44 S initiation intermediate. In the presence of IF-II and a suitable RNA template, the 44 S initiation intermediate combines with a 60 S ribosomal subunit to form a functional 80 S initiation complex. The methionyl moiety of the initiator tRNA in the 80 S initiation complex is able to react with puromycin to form methionylpuromycin.


Metal-polynucleotide interactions. A comparison of carcinogenic and non-carcinogenic metals in vitro. The effects of divalent cations on mixing curves of synthetic polyribonucleotides in solution are described. Manganese and cadmium chlorides at 10(-3) M induce changes suggestive of base mispairing. MnCl2 induces mispairing in complexes formed between both poly(I) and poly(C,U) and poly(I) and poly(C,A) while CdCl2 affects base pairing between poly(I) and poly(C,U) only. By contrast, the chlorides of magnesium and zinc show no mispairing effects with either polymer pair. Manganese and cadmium are both reported carcinogens in animals while magnesium and zinc are not. The possibility that direct metal-nucleic acid interaction may be involved in metal carcinogenesis is discussed.


Measurement and interpretation of fluorescence polarisations in phospholipid dispersions. An instrument that measures the temperature dependence of fluorescence polarisation and intensity directly and continuously is described. The behaviour of four fluorescent probes bound to a number of well characterised model systems was then examined. The motional properties of the probes were determined from the polarisation and intensity data and were found to be sensitive to the crystalline-liquid crystalline phase transitions in phospholipid vesicles of dimyristoly and dipalmitoly phosphatidylcholine. Binary mixture of dilauroyl and dipalmitoyl phosphatidylcholine show lateral phase separation and in this system the probes parition preferentially into the more 'fluid' phase. In systems that have been reported to contain 'short range order' or 'liquid clustering', such as dioleoyl phosphatidylcholine and liquid paraffin, the motion of the probes was found to have anomalous Arrhenius behaviour consistent with the idea that homogeneous phases were not being sampled. The significance of these findings for the interpretation of the behaviour of fluorescent probes bound to natural membranes is discussed.


Photobleaching. A novel fluorescence method for diffusion studies in lipid system. (1) The fluorescent molecular 12(9-anthroyloxy)-stearic acid dimerises on irradiation with light of 366 nm wavelength. (2) The dimer is nonfluorescent and can be reconverted to the parent compound by irradiation at 254 nm. (3) Kinetic analysis suggests that the dimerisation proceeds by a diffusion-limited second order mechanism in many solvents. (4) Anomalously high rates seen in other systems can be attributed to localised high concentration regions (clusters) of the fluorescent molecule. (5) The analysis has been extended to oriented lipid bilayers and the results suggest that below the gel-liquid crystalline transition temperature the 12(9-anthroyloxy)-stearic acid is excluded by the lipid matrix and forms regions of localised high concentration. (6) In fluid lipid the results suggest an isotropic distribution of the probe. Calculated diffusion coefficients correspond to those found by other techniques.


Isolation of a synaptic membrane fraction enriched in cholinergic receptors by controlled phospholipase A2 hydrolysis of synaptic membranes. A procedure is described for the isolation of synaptic membrane fragments that retain such functionally important proteins as acetylcholine receptors, acetylcholinesterase, 3',5'-cyclic nucleotide phosphodiesterase, and (Na+ + K+)-ATPase. The method is based on the observation, made in brain slices, that junctional membranes are more resistant to phospholipase A2 attack than mitochondrial or plasma membranes. Hydrolysis by phospholipase A2 was controlled by addition of fatty acid-free bovine serum albumin. The membrane fraction obtained represents approximately a 15-fold enrichment of the postsynaptic marker proteins muscarinic and nicotinic acetylcholine receptor and 3',5'-cyclic nucleotide phosphodiesterase over an ordinary synaptic plasma membrane preparation, and is devoid of mitochondrial and microsomal contaminations. The membranes appear on the electron micrographs as rigid fragments (average length 2500-4000A), which do not form vesicles.


Heterogeneity in the fluidity of intact erythrocyte membrane and its homogenization upon hemolysis. Intact erythrocytes were spin-labeled with various classes of phospholipid label. The ESR spectrum for phosphatidylcholine spin label was distinctly different from those for phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol and phosphatidic acid spin labels. The overall splitting for the former (52.5 G) was markedly larger than those for the others (approx. 47 G), suggesting a more rigid phosphatidylcholine bilayer phase and more fluid phosphatidylethanolamine and phosphatidylserine phases in the erythrocyte membrane. Evidence for asymmetric distribution of phospholipids in the membrane was obtained. Spin-labeled phosphatidylcholine incorporated into erythrocytes was reduced immediately by cystein and Fe3+, while the reduction of spin-labeled phosphatidylserine was very slow. The present results therefore suggest asymmetric fluidity in erythrocyte membrane; a more rigid outer layer and a more fluid inner layer. The heterogeneity in the lipid structure was also manifested in the temperature dependence of the fluidity. The overall splitting for phosphatidylcholine spin label showed two inflection points at 18 and 33 degrees C, while that for phosphatidylserine spin label had only one transition at 30 degrees C. When the spin-labeled erythrocytes were hemolyzed, the marked difference in the ESR spectra disappeared, indicating homogenization of the heterogenous fluidity. Mg2+ or Mg2+ + ATP prevented the hemolysis-induced spectral changed. Ca2+ did not prevent the homogenization and acted antagonistically to Mg2+. The heterogeneity preservation by Mg2+ was nullified by trypsin, pronase or N-ethylmaleimide added inside the cell. Some inner proteins may therefore be involved in maintaining the heterogeneous structure. The protecting action of Mg2+ was dependent on hemolysis temperature, starting to decrease at 18 degrees C and vanishing at 40 degrees C. The present study suggests that the heterogeneity in the fluidity of intact erythrocyte membranes arises from interactions between lipids and proteins in the membrane and also from interactions between the membrane constituents and the inner proteins. Concentration of cholesterol in the outer layer may also partly contribute to the heterogeneity.


Characterization of the mycoplasma membrane proteins. VI. Composition and disposition of proteins in membranes from aging Mycoplasma hominis cultures. Membranes of Mycoplasma hominis cells from cultures progressing from the mid to the end of the logarithmic phase of growth became richer in protein, poorer in phospholipids and cholesterol, heavier in density, and more viscous as determined by EPR. The membrane-bound ATPase activity declined steeply. Electrophoretic analysis failed to show marked changes in membrane protein composition on aging, apart from an increase in the staining intensity of one protein band (Mr approximately 130 000) concomitant with a decrease in the staining intensity of several minor protein bands of high molecular weight. To test for possible changes in the disposition of the various membrane proteins on aging of cultures, a comparison was made of the susceptibility of membrane proteins of intact cells and isolated membranes to trypsinization and lactoperoxidase-mediated iodination. The iodination values and the percent of membrane protein released by trypsinization of intact cells were similar in cells from cultures of different ages, indicating no significant changes in the organization of the proteins on the outer surface. On the other hand, trypsinization and iodination of isolated membranes were found to be most markedly affected by the culture age, indicating significant changes in the organization of the proteins on the inner membrane surface. Thus, the iodination values of isolated membranes decreased by almost two fold, while the percentage of protein released from the membrane by trypsin increased from 28% to 50% during the experimental period. It is suggested that aging in M. hominis cultures is accompanied by a continuous increase in the packing density of the protein molecules on the inner surface of the cell membrane.


Evidence for an inducible glucose transport system in Kluyveromyces lactis. To find the cause of delayed glucose oxidation in succinate-grown Kluyveromyces lactis, glucose transport was studied in glucose- and in succinate-grown cells. The initial rate of 2-deoxyglucose (2-dGlc) accumulation, as well as the appearance of 2-deoxyglucose 6-phosphate, was higher in the glucose-grown cells. In both cell types, 2-dGlc was apparently transported in the free form to be phosphorylated intracellularly. In glucose-grown cells the level of free 2-dGlc in the pool was always less than the external concentration. Exchange transport in starved, poisoned cells loaded with unlabeled 2-dGlc was 140-fold greater in glucose- than in succinate-grown cells, probably beacuse of the presence of an inducible transport component. The development of the increased rate of transport in a succinate-grown uracil-requiring auxotroph after transfer to glucose depends on the presence of uracil.


Effect of sodium deoxycholate on 5'-nucleotidase. The 5'-nucleotidase localized in rat liver plasma membranes was purified to a single protein, which contained phospholipid. The molecular weight and the sedimentation constant were about 150 000 and 7 S in the presence of sodium deoxycholate, while the enzyme protein was aggregated when the preparation was dialyzed thoroughly. The purified 5'-nucleotidase exhibited the same properties as the 5'-nucleotidase in plasma membranes. The 5'-nucleotidase activity was increased by the addition of various bile salts or by the solubilization of membranes with trypsin, papain or phospholipase C. The solubilized and aggregated forms of the enzyme showed different substrate specificity for nucleotides, pH optimum, heat stability and Km. The purified enzyme catalyzed an exchange reaction between AMP and adenosine, which was diminished by the addition of sodium deoxycholate.


Jejunal and ileal D-glucose transport in isolated brush border membranes. D-Glucose transport was investigated in isolated brush border membranes from small intestine. The transport properties of membranes from upper jejunum were compared with those from terminal ileum. The jejunal membranes accumulate D-glucose to a greater extent than the ileal membranes when supplied with energy in the form of a NaSCN gradient. This difference in behavior is similar to that of the more intact epithelial preparations and suggests that the isolated membranes actually reflect the state present in intact cells. Ileal membranes transported D-glucose about two to three times slower than the jejunal ones, which can partially explain the lower sugar accumulation.


[Role of quasiclassical subsystems in an elementary act of enzymatic catalysis]. The acceleration mechanism of the enzymatic reaction as a result of deformation of state spectrum functionally active region under the effect of the field of quasiclassical subsystem is discussed in terms of the approach developed.


[Specific resistance and electrophoretic mobility of regenerating liver cells. Effect of ribonuclease and neuraminidase]. Changes of specific resistance and electrophoretic mobility of the cells from regenerative liver of rats are investigated. It is shown that specific resistance decreases and electrophoretic mobility increases during 30 h after hepathectomy. Exogenous ribonuclease decreases electrophoretic mobility by 10% and does not reduce significantly specific resistance. Neuraminidase treatment caused a marked increase (approximately 40%) of specific resistance without reduction in the mobility of cells from both intact and regenerative liver. It is concluded that there is no difference in the sensitivity of the cell surface of normal and regenerative liver to ribonuclease and neuraminidase.


[Chromatic fluorescence transitions in bean chloroplasts]. Chromatic fluorescence transients of isolated bean chloroplasts were investigated. In the presence of methylviologen we observed a decrease in the chloroplasts fluorescence under the influence of light which mainly excited the photosystem I. The effects of preliminary illumination with the white light and Mg2+ ions concentration on the fluorescence of chloroplasts were also studied.


[EEG potential theory in a model with thin brain integuments. I. Multilayer spherical cable model]. The problem of finding EEG potentials is solved assuming that integuments of the brain are regarded as infinitely thin spheres. The potential is not changed along the radius in the layers with high conductivity, and the current in the resistive layers is only radial. It is shown that the EEG potentials could be described exactly enough supposing the lower bone plate to be an ideal isolator. The potentials of EEG are obtainable from ECoG by means of a comparatively simple algebraic procedure.


[Principles of neuronal organization. II. Information capacity of Purkinje cells and climbing-nuclear cerebellar unit]. On the ground of the author's information-theoretic approach to the neuronal memory informational capacity of P-cell is evaluated. The values of one and 1n2 bit/synaps are obtained in different cases. The latter case corresponds to most probably situations. In this case P-cells exhibit a great degree of false memory -- only 10% of the information presented to the cell is preserved. There is considered also a functional group of few P-cells governed by common climbing and mossy fibres and different granula cells. In this functional unit all the information presented is preserved with the efficiency of 1n2 bit/synaps. The scheme is of the class proposed by Cowan and Winograd. It is thought that the real cerebellum operates according to the proposed ideas.


[Basilar membrane nonlinearity].

[Basilar membrane nonlinearity]. The nonlinear correction of the cochlear partitions movement equation becomes the main part in the resonant section. In the neighbourhood of this section the periodic solution, having the drawing force frequency omega, gets the region of the non-stability in the interval (see abstract), where a is the vibration amplitude and h is the basilar membrane thickness. The amplitude jump in the unstable region may be a stimulus exciting the hair cells and also the cause of cochlear eddies phenomenon.


[Constant representation of signal spatial location in the cricket cercal system]. Directional sensitivity of the abdominal giant fibers of the cricket to auditory stimulation has been investigated with special interest to the effect of the cerci position on the directional sensitivity of the giant neurons of the terminal abdominal ganglion. It has been shown that at least for some giant neurons the preferred directions of stimulation are practically independent of cerci position. (Fig. 2, 3). By other words these neurons have constant preferred directions in relation to the insect body, but not to the cerci. This property of giant neurons can be accounted for their changeable connections with many receptors having different directional selectivity. If innervation of the giant neuron is artificially restricted to one group of receptors with identical directional selectivity the described constancy of preferred directions in relation to the body disappears (Fig. 4).


[Possible mechanisms of information interactions in molecular physico-biological systems]. Cooperative mechanisms of information transfer in molecular physico-biological systems are suggested. Expressions for probability of cooperative emission from interacting molecules having quite definite information about the character of distribution of molecules inside the system are derived. The suggested mechanisms of information transfer on the atomic-molecular level will possibly allow to understand better and to describe adequately many interesting phenomena considered by molecular biology and molecular psychobiology in particular. Appendix: Throbbing in cooperative luminescence for triads of molecules combined with each other by weak interaction.


[Work of the human visual system. III. Color perception space]. In the previous parts of this work the author presented thet expression for percieved colour: Ei=k1n(ai/ao) where k -- is the coefficient of proportionality which have dimension of sensation and ai, ao -- are the light actions in some retinal point and in the extreme periphery correspondingly. Here the author describes some consequences from this expression and gives a new conception about the space of colour sensations.


[Receptive field types  in the lateral geniculate body and their frequency characteristics]. Time amplitude -- frequency characteristics of the I and II types of receptive fields (RF) of lateral geniculate and their dependence on the contrast and spatial parameters of the light stimulus were studied. It is shown that the frequency characteristics of the RF I type depends on the contrast and area of the light stimulus, the higher being the contrast at a small area the smaller are the low frequencies. However at a large area of the stimulus the inhibition of low frequencies is greater at a small contrast. The transmitting band of frequency characteristics of RF II type does not depend on the contrast at a small area of the stimulus, at a large area a fall of low frequencies takes place at high contrasts of the stimulus. Such different behaviour of the receptive fields is explained by the models, which take into account RF spatial characteristics.


[Trophic level equations and statistical mechanics of biocoeneses]. Equations for the biomasses of trophical levels are presented. Analytic solutions for biomasses of trophical levels and several species of biomasses are obtained near the stationary state. The distribution function for species of biomasses is built.


[Generalization of the Lotka-Volterra equation]. A complete qualitative study of Lotka--Volterra model with cooperative interactions in the system predator-prey is carried out. The model is as follows: (see abstract). The character of all possible stationary states is investigated in the first quadrant of the phase plane of the model variables depending on the system parameters. It is shown that for the generalized model considered unstable and stable limit cycles only of the infinite amplitude are possible in the first quadrant.


[Phase transition in natural collagen].

[Phase transition in natural collagen]. The state of water protons and peptide chains in natural collagen was investigated by the method of nuclear magnetic resonance. The study of orientation and temperature dependence of collagen PMR spectra allows us to mage a conclusion about the considerable disorder of mutual orientation in the polypeptide chains at the temperature above -4 degrees C. Under these conditions it was observed that natural collagen was near to the liquid-crystal. The phasic transition at -4 degrees C was discovered, the latter was followed by an abrupt change of the character of water proton mobility and by the change of orientation of collagen fibres order. The thermal effect of transition was measured, the latter presents 18k/gr of the whole specimen.


Excited complexes in oxidation-reduction photoreactions of pigments. I. Spectral detection of triplet state exciplex in the chlorophyll oxidation reaction. Photooxidation of chlorophyll "a" with p-benzoquinone in toluene and dioxane is studied by the method of flash photolysis. It is shown that in nonpolar medium the triplet exiplex is the product of this reaction. The experiments on competitive quenching of chlorophyll triplet state with naphthacene prove the diffusion mechanism of exiplex formation. The spectrum of triplet-triplet absorption of the exiplex is presented and the rate constant of intercombination degradation equalling 1.103 sec(-1) is measured. Possible structure of the exiplex is discussed.


[Ferredoxin reduction by polarographic methods]. The reduction of iron-sulphur protein of the higher plant ferrodoxin has been studied by polarographical methods. Ferredoxin initiates a reversible wave with E1/2=--0,61 v (N. C. E.) at pH 7. Protein absorption greatly influences the electrochemical reduction. The protons have been shown to take part in the electrode reaction. The potentiometrically obtained data about the difference between E1/2 and E0=--0.70 v and its causative factors are discussed. As a result of the experiments with modification of ferredoxin active centre it has been concluded that the active centre participates in the polarographical reduction.


[Effect of the spectral composition of light on the mechanism of reaction of chlorophyll oxidation]. Photochemical oxidation of chlorophyll "a" on excitation of the pigment in different spectrum region (400-800 nm) was studied by flash photolysis. The absorption spectrum of chlorophyll cation-radical Chl+ was obtained and the values of extinction coefficient found. An attempt was made of photochemical generation of dication form of chlorophyll. Thermodynamical calculation supporting the possibility of the following reaction is presented: (Chl+)*+Ae -- Chl2""Ae. The absence of Chl2+ is explained by a short life time of the excited cation-radical of chlorophyll (Chl+)*. The effect of the wave length of excited light on the kinetics of the decay of chlorophyll cation-radical is studied. It is shown that on excitation of chlorophyll "a" with white light the life time of Chl+ decreases and its death is described by an equation of first order, which is explained by the formation of ion-radical of the electron acceptor resulting from the direct excitation of Ae.


[NMR spin-echo study of the effect of hydration on the mobility and conformation of linear polyethyleneimine]. It has been shown that mobility of protons in different groups of linear polyethylenimine (LPEI) is sensitive to the formation of H-bonds between amino groups of a polymer. Upon hydration of LPEI most of direct bonds between amino groups are substituted by the bonds via water molecules. This results in a conformational change of the polymer. Similar process may also occur in biopolymers.


[Mechanism of photochemical oxidation of bacterioviridin]. The mechanism of bacterioviridin photochemical oxidation has been studied by the methods of ESR, flash-photolysis and low-temperature spectrophotometry. ESR spectrum of pigment cation-radical, a singlet line with H=11 G, g = 2.0027, has been recorded. The bands with maxima at 370, 470, 525, 590, 840 nm correspond to bacterioviridin cation -- radical in the absorption spectra. When -- benzoquinone is used as an electron acceptor with excitation light 640 nm the product of bacterioviridin irreversible oxidation is formed with the absorption band maximum 760 nm and absorption between 350 and 370 nm. It is suggested that this product is of double-oxidized non-radical nature and the mechanism of its formation through oxidation of the pigment cation-radical is discussed. The regeneration reaction of double-oxidized bacterioviridin up to cation-radical form in the presence of triphenylamine as a reducing agent has been carried out. The rate constants of cation-radical decay in the dark and desactivation of triplet state have the following values: K1=(1,64+/-0,15)-10(3) sec-1, K2=(13+/-2,0)-10(3) sec-1 correspondingly. The activation energy of the radical decay in the dark is Eact =(13,2-0,5) kcal/mole.


[Polarographic study of quinones formed during oxidation of caffeic and chlorogenic acids]. Polarographic behaviour of a number of substituted ortho-benzenquinones was studied in weakly acidic, neutral and weakly caustic solutions (up to pH --9.0). Half-wave potential depends on the solution pH, indicating protonization of the carbonyl groups of the quinones. Protonization is probably stipulated by the hydroxonium ions. Protonization may take place not only under the action of water, but also under the effect of other acidic components, as indicated by the dependence of E1/2 on the undissociated acetic acid centrifugation. The condensation and polymerization reactions are characteristic for the ortho-quinones. A shift of the quinone potential indicates dimerization of the electrode products.


[Modeling of ion transport. Analysis of possible mechanisms of intracellular osmoregulation]. It seems likely that the operation of the vacuolar mechanism of active transport of water (VMATW) is based on the following. An exceeding osmotic pressure is created within an originally small vacuole (e. g. due to rapid enzymatis hydrolysis of macromolecules inside the vacuole) and consequently water enters the vacuole, as well as molecules and ions according to the gradients of their chemical potentials. After a while the contents of the swelling vacuole is thrown out to the external medium. An analysis of the efficiency of VMATW system in the stationary case shows that the efficiency of VMATW can be rather high to create the ionic heterogeneity.


[Electrochemical model of enzyme oxidation-reduction reactions with a limiting stage of electron transfer]. Enzymatic redox reaction is modelled by a set of microgalvanic elements shorted out. It allows to use as the rate constant of enzymatic reaction the rate constant deduced for the electrode reaction with a limiting stage of electron transfer. The basic problem is to determine the nonequilibrium potential by the phase border enzyme/solution. A phenomenological model for determining the nonequilibrium adsorption dependent potential is suggested. The rate constant is deduced which depends on the adsorption of one of the substrates (activation or inhibition). This dependence is the same for the whole set of adsorption isoterms. A class of well known relationships of the initial rate of enzymatic reaction and the substrate concentration is obtained for a simple case of physical adsorption.


[Fluorescence analysis study of the lability of biomembranes and their components. III. Kinetics of complex formation between bovine serum albumin molecules and higher saturated fatty acids]. Kinetic peculiarities of the sorption of natural limited fatty acids on the molecules of bovine serum albumine (BSA) were studied by investigating fluorescent parameters of ionic (1-anilinonaphtalin-8-sulphonate-ANS) and neutral (N-phenyl-1-naphtylamine-PNA) probes. The following regularities were found: 1. The parameters which characterize the microsurroundings of both probes (quantum yield of fluorescence, the binding constant) did not change significantly during the sorption of the fattyn acids (laurinic, palmitinic and methyl ether of the stearinic acid). An exponential character of BSA fluorescent titration with fatty acids points to a competitive character of the relationship dye -- fatty acid for the binding sites in hydrophobic sacks of BSA. 2. The study of the character of the effect of solution ionic strength on the sorption of fatty acids showed that along with hydrophobic interactions the electrostatic interaction between carboxyl residues of fatty acids and charged protein groups also significantly contributed to this process. 3. Temperature relationship of AMS and PNA fluorescence intensity in the complex BSA -- laurinic acid correlates well with temperature relationship obtained from a pure protein system.


[Physical model of an electroexcitable membrane. I. Volt-ampere characteristics]. In a series of papers an attempt is made to develop the elementary physical model of excitable membrane structures. The present communication deals with the nature of N- and S-type voltage-current relations of the resting membrane. Simple analytical forms obtained for these relationships are in good accord with the experimental data.


[Electrogenesis in a model of "boundary transport" in the sodium pump]. An equation of the membrane potential (MP) was developed for a model of sodium pump when it was assumed that a macromolecule-carrier operated on the interior boundary of the membrane exchaning Na+i for K+ of membrane. These ions then moved downhill the electrochemical gradient inside the membrane. There are factors in the equation which indicate energetical consumtions for the ionic exchange. In was shown that an exchange of 3Na+ for 2K+ required 9,0 kkal/mole. The equation satisfactorily describes experimental values of MP during the electrogenic active transport. After all it was shown that an alteration of MP for 100 mV did not affect the operation of sodium pump i.e. the influence of outer electrical field was not detected.


[Use of rare-earth elements as labels for studying biologically active compounds. IV. Luminescence spectra and structure of compounds of europium with nucleotides]. Spectra of europium coordinating nucleotides are investigated. Europium is shown to coordinate phosphate, but the way of coordination may change. Conditions of nitrogen bases coordination are determined. The evidence or the existence of coordinated immobilized water is found.


[Overrelaxation of muscle models in media with high concentrations of calcium ions and exposed to MgATP in "contraction-inducing" concentrations]. Cross-striation pattern and sarcomere length in isolated myofibrils (both glycerinated and fresh) as well as isometric tension of glycerinated fibers of rabbit m. psoas are unaffected by an evaluation in ionic strength of CaCl2 up to 0.2 in the absence of ATP. An addition of MgATP (1 to 3mM) to the Ca2+ media induces the changes which have been shown to be characteristic of overrelaxation [1, 2]: A band shortening occurs followed by a complete plastification of the fibres. A tentative mechanism of the process is discussed in terms of spontaneous rearrangement of calcium myosinate packing in thick filaments that follows disrupting of rigor crossbridges with thin filaments under the action of ATP. Released calcium myosinate heads fail to form "active" bridges with actin; thick filaments undergo a conformational change resulted in their shattening due to increase in the equilibrium region of LMM tail overlap. The effects do not depend on ionic strength only: on replacing CaCl2 by KCl at equal ionic strength 0.2, an addition of ATP induces normal contraction instead of overrelaxation. A possibility is discussed that in a living muscle overrelaxation could provide a siding to prevent damage in case of emergency.


[Graph of sodium channel states].

[Graph of sodium channel states]. Four models of sodium channel are considered, only one of its state being conducting. Transitions between any two communicated states are suggested to be governed by the first order kinetics. It is shown that the model describes current responses to single step potentials as well as inactivation -- activation coupling, if its graph has a function between the conducting and inactivation states and the state filled at the hyperpolarization.


A review of the methods of processing EMG for use as a proportional control signal. The use of EMG as a proportional control signal for prostheses is reviewed. The lack of success of existing proportional EMG-controlled prostheses is shown to be attributable in the greater part to the presence of low frequency "noise" in the processed EMG signal. If EMG is to yield useful proportional information, this noise must be eliminated, and to this end the methods of processing EMG are reviewed and the sources of noise examined. A number of methods for its removal are discussed.


An ECG telemetry system for physiological studies on swimmers. A low frequency telemetry system is described which has been designed to allow high quality ECG measurements to be made on active swimmers. The transmitting antenna is a small loop worn by the swimmer whilst the receiver is fed from a single wire loop around the swimming pool. Both ECG electrodes and the transmitter case are made in a waterproof form which allows the swimmer complete freedom of action to dive and swim normally. The transmitter can be constructed from normal miniature components although the present version has been assembled using thick film techniques which combine high reliability with a reduction in overall volume.


The influence of surface rugosity on haemolysis occurring in tubing. Haemolysis was measured in three tubes of the same chemical composition but differing surface texture. It was found that during the first hour of pumping the increase in haemolysis in both human transfusion blood and fresh cattle blood was greatest in the roughest tubes. When pumping of blood was continued for longer periods the rate of further haemolysis increase was equal in all tubes.


Automated adsorption isotherm device.

Automated adsorption isotherm device. A device is described for the automated determination of the water adsorption isotherms of biological materials. The vapor pressure and weight of the adsorbate are measured directly with appropriate transducers, and equilibrium is defined on the basis of constant pressure. The accuracy of the device, determined on two samples with well-known water binding properties, is +/- 5%. Automation is achieved by electronic control.


Transport calculations for light scattering in blood. In vivo measurement of the oxygen saturation levels in blood may be obtained from relative amounts of backscattered monochromatic light at two different wavelengths, as measured with a fiber-optic catheter oximeter. Because of the short mean free path length of light in blood, the backscattering can be well approximated by a previously-derived, one-wavelength transport theory solution for the half-space searchlight problem. This solution, unlike simple diffusion approximations has the advantage that the boundary condition describing illumination of a localized area of blood by a monodirectional light beam can be rigorously satisfied. Sample calculations using the solution are compared with experimental values of the reflectance of blood.


Anodal excitation in the Hodgkin-Huxley nerve model. Computations show that cathodal rheobase increases with temperature from 0 degrees C to 30 degrees C. Anodal rheobase (stimulation at the end of an indefinitely long anodal pulse) also increases with temperature, but goes to infinity at a critical temperature 17.13 degrees C, above which such excitation is impossible. For a stimulus consisting of any step change of current from I0 to I1, a threshold curve of I1 is plotted against I0. As the temperature increases, this curve rises. Its intersection with the horizontal axis, which determines the anodal rheobase, goes to infinity at the critical temperature. This phenomenon is caused by the saturation of the variables m, h, n for strongly hyperpolarized potentials, combined with the relative speeding up of the inhibitory process with increasing temperature. The threshold charge Q in an instantaneous anodal current pulse (of zero duration) goes to infinity at the same temperature, with a similar explanation in terms of threshold curves in the I1 vs. Q plane. The fact that the critical temperature for both cases is the same is generalized by the conjecture that for any anodal current waveform whatever, as its amplitude approaches infinity, the trajectory in the phase space following its cessation approaches the same limiting trajectory. This limiting trajectory changes from suprathreshold to subthreshold at the critical temperature.


Mathematical description of a bursting pacemaker neuron by a modification of the Hodgkin-Huxley equations. Modifications based on experimental results reported in the literature are made to the Hodgkin-Huxley equations to describe the electrophysiological behavior of the Aplysia abdominal ganglion R15 cell. The system is then further modified to describe the effects with the application of the drug tetrodotoxin (TTX) to the cells' bathing medium. Methods of the qualitative theory of differential equations are used to determine the conditions necessary for such a system of equations to have an oscillatory solution. A model satisfying these conditions is shown to preduct many experimental observations of R15 cell behavior. Numerical solutions are obtained for differential equations satisfying the conditions of the model. These solutions are shown to have a form similar to that of the bursting which is characteristic of this cell, and to preduct many results of experiments conducted on this cell. The physiological implications of the model are discussed.


Comparison of two-pulse sodium inactivation with reactivation in Myxicola giant axons. Values for the time constant of reactivation of the sodium conductance following depolarization sufficient to completely inactivate GNa have been compared over a 15 mV range of membrane potential with the time constants of inactivation during a depolarization prepulse. Over this range the reactivation time constants were consistently 30-50% larger than the inactivation time constants determined simultaneously at the same potential in the same axon. The data suggests that inactivation and reactivation do not occur by identical mechanisms, and therefore implies that there are at least three kinds of experimental procedures necessary to fully characterize the sodium inactivation process in any particular system.


Chemotaxis in vitro. Quantitation of human granulocyte movement using a stochastic differential equation. The quantitation of human granulocyte movement using a stochastic differential equation is described. The method has the potential to distinguish both positive and negative chemotaxis. Analysis and information concerning cell movements can be obtained for any point in time and distance for the duration of the experiment.


Effect of age on passive elastic stiffness of rat heart muscle. A thick-wall spherical model for the rat left ventricle was used to deduce passive wall stiffness from diastolic pressure-volume data. This was done for rats in three age classes: young (1 mo), adult (17 mo) and old (17 mo). The model was based on finite deformation elasticity theory consistent with the magnitude of observed deformation. A least-squares procedure was used to determine elastic constants in postulated nonlinear stress-stretch relations for the myocardium. It was found that at a given level of stress, wall stiffness for ventricles in the young age class was consistently greater than wall stiffness in the other two classes. In addition, the difference in wall stiffness between rats in the adult and old age classes was found to be approximately 10%.


An assessment of a coupled three-state kinetic model for sodium conductance changes. The behavior of a coupled three-state kinetic scheme is examined to see if it might be a viable model for the conductance changes of sodium channels. It is found that for simulations of experiments which determine the properties of the Hodgkin-Huxley m and h gates, the three-state scheme performs approximately equivalently to the Hodgkin-Huxley model. In particular, the three-state scheme successfully simulates those experiments which the Hodgkin-Huxley model successfully simulates, but fails to simulate those newer voltage clamp experiments which give results anomalous to the H-H model. It is concluded that the three-state scheme is probably as good as the H-H model, but is not a viable successor to it.


Lethal response of HeLa cells to x-irradiation in the latter part of the generation cycle. The age-response for the killing of HeLa S3 cells by X-rays during the latter part of the generation cycle has been examined in detail. As synchronous cells move from the G1/S boundary through S phase, the relatively high sensitivity of late G1 cells gradually decreases; minimum sensitivity is reached in mid-S and maintained during the remainder of that phase. The response of cells as they progress from S to the point in G2 at which they are temporarily arrested by radiation (or by inhibitors of protein synthesis) was measured in populations free of both S phase cells and late G2 cells that had passed the arrest point: cells retain their high resistance from early G2 up to the arrest point. The response of G2 cells that have passed the arrest point before being irradiated was examined by exposing randomly growing cultures to X-rays and collecting cells periodically thereafter, as they entered mitosis. Survival values very close to those of sensitive mitotic cells were found in the 2 h period after irradiation during which unarrested cells continued to reach mitosis. Values typical of lateS/early G2 were found only after cells that had been arrested began arriving at mitosis. Thus, HeLa S3 cell undergo an abrupt increase in sensitivity at or near the arrest point. The sensitivity to a second irradiation of cells arrested in G2 by a conditioning X-ray dose increases rapidly in the early part of the arrest period.


Electrical conductivity in lipid bilayer membranes induced by pentachlorophenol. Electrical conductivity induced in thin lipid bilayer membranes by pentachlorophenol has been studied. The membranes were formed from phosphatidyl choline, phosphatidyl ethanolamine, or phosphatidyl glycerol and various amounts of cholesterol. The position and the magnitude of the maximum of the conductivity vs. pH curve depend on the type of lipids and cholesterol content. At low pentachlorophenol concentrations and low pH the concentration dependence of conductivity is quadratic and becomes linear at higher pH. Above 10(-5) M of pentachlorophenol the concentration dependence of the membrane conductivity tends to saturate. Presence of pentachlorophenol enhances membrane transport of nonactin-K+ complex. Increase of cholesterol content increases pentachlorophenol induced conductivity in all membranes and shifts the conductivity toward lower pH. For phosphatidyl choline the largest rate of change of membrane conductivity with cholesterol occurs at 1:1 phospholipid to cholesterol molar ratio. Pentachlorophenol is found to be a class II uncoupler and the experimental results are consistent with the hypothesis that the membrane permeable species are dimers formed by combination of neutral and dissociated pentachlorophenol molecules. Several schemes of membrane conduction, including dimer formation in the aqueous phase as well as at the membrane-water interface have been considered. Arguments are given in favor of the formation of dimers within the membrane surface.


A light-scattering characterization of membrane vesicles. A technique has been developed in this paper which enables quasi-elastic laser light scattering to be used to accurately and quantitatively measure the average vesicle diffusion coefficient and the relative dispersion in the diffusion coefficient about this average for dilute polydisperse vesicle suspensions. This technique relies on a theoretical analysis of a modified form of the Z-averaged diffusion coefficient. This modified Z-averaged diffusion coefficient explicitly incorporates vesicle size, structure, and polydispersity in a description of the scattered light autocorrelation spectrum. Light-scattering experiments were performed on a dilute, lobster sarcoplasmic reticulum vesicle suspension and the measured average diffusion coefficient and the diffusion coefficient relative dispersion about this average were determined with accuracies of 2 and 10%, respectively. A comparison of vesicle size inferred from light-scattering results was made with size results from electron microscopic analysis of the same sample.


The application of constant recycle solids concentration in activated sludge process. The applicability of the model derived by Ramanathan and Gaudy (Biotechnol. Bioeng., 11, 207, (1969)) for completely mixed activated sludge treatment holding the recycle solids concentration as a system constant was investigated using an actual industrial organic wastewater. Short-term experiments were conducted at various dilution rates (1/8, 1/6, 1/4, 1/2, 1/1.5 hr-1) for two recycle solids concentration values (5000 and 7000 mg/liter). The influent substrate concentration was maintained at 1000 mg/liter COD and the hydraulic recycle ratio- alpha, was kept at 0.3. It was found that for bottling plant (Pepsi Cola) wastewaters, a steady state with respect to reactor biological solids and effluent COD, at different dilution rates, could be attained, lending experimental evidence to the assumption that a steady state could be reached in developing the model and also affecting the applicability of the model in industrial organic wastewater. The reactor biological solids and effluent COD calculated from the model closely agreed with the observed values at dilution rates lower than 0.5 hr-1. Operation at dilution rates higher than 0.5 hr-1 will washout the biological solids from the reactor and the recycle substrate concentration will be apparent if the concentration of XR were not increased.


Transient response of Enterobacter aerogenes under a dual nutrient limitation in a chemostat. Utilizing a chemostat with a dual nutrient limitation of nitrogen and phosphate, we examined the transient response of the culture following a pulse of one of the limiting nutrients (ammonia). This method provided quantitative evidence that cells can be grown under dual nutrient limitation. Furthermore, the pattern of response was consistent with the hypothesis that phosphate limitation restricts nucleic acid synthesis in the cell and that nitrogen limitation restricts protein synthesis. The net result is that under a phosphate limitation there is a restricted biosynthetic capacity which we feel is closely associated with the RNA content of the cell.


Conversion of L-sorbose to L-sorbosone by immobilized cells of Gluconobacter melanogenus IFO 3293. Gluconobacter melanogenus IFO 3293 cells capable of converting L-sorbose to L-sorbosone were immobilized in polyacrylamide gel. The preferred polymer composition for high activity and stability was determined to contain a total monomer concentration of 7.2% and 16.6% crosslinking agent. No significant differences in optimal conditions for conversion, e.g., pH and temperature, were found in comparison with free cell suspensions. However, in the absence of L-sorbose, the thermal stability of immobilized cells was lower. After the initial loss, the conversion activity of immobilized cells increased, possibly due to lysis, and this increase was related to the polymerization conditions and the incubation temperature for the L-sorbose conversion. The enzymatic activity and stability of the immobilized cells also depended on the physical form of the gel and the aeration levels. Addition of electron acceptors or addition of L-sorbosone to the medium reduced, while addition of neomycin, ampicillin, chloramphenicol, and tetracycline increased the stability of the enzymatic activity.


Effect of a congenital defect in hemopoiesis on myeloid growth and the stem cell (CFU) in an in vivo culture system. W/Wv mice with congenitally defective CFU proliferation and their normal, congenic littermates were used as hosts for diffusion chamber (DC) implants. CFU growth in implanted allogenic CF1, or congenic +/+ marrow was significantly greater in W/Wv than in control hosts. When W/Wv mice were "cured" of their hemopoietic defect, CFU proliferation in the DCs decreased, but not to the control level. These observations have provided evidence for humoral control of CFU growth related to a genetic stem cell defect. Diffusion chamber myelopoiesis was also enhanced in W/Wv hosts. In comparison with their congenic controls, W/Wv mice were neutropenic and had decreased numbers of marrow myeloid elements. Thus, a humorally mediated feedback related to a defective myelopoiesis in the hosts might have accounted for increased DC myelopoiesis. However, a "spillover" effect from increased stem cell growth has not been excluded.


Differences in free fatty acid and glucose metabolism of human blood neutrophils and lymphocytes. Comparison of isolated human neutrophils and lymphocytes in short-term tissue culture revealed marked differences in their rates of lipid biosynthesis. Ficoll-Hypaque gradients were used to separate lymphocytes and neutrophils from the blood of normal subjects. Neutrophils incorporated more palmitate into cell lipids (151.0 +/- 16.6 nmole/hr/10(8) cells) than lymphocytes (41.6 +/- 4.1). By contrast, the lymphocytes oxidized more palmitate (8.3 +/- 0.5 nmole/hr/10(8) cells) as compared to neutrophils (1.1 +/- 0.1). The greater fatty acid uptake by the neutrophils was due to a sixfold greater rate of incoporation of palmitate into their triglyceride fraction. Triglyceride synthesis by neutrophils increased as the molar ratio of free fatty acid to albumin was raised, whereas incorporation into phospholipids remained relatively constant; there was preferential labeling of neutrophil triglycerides throughout the physiologic range. Studies using linoleate and oleate gave similar results. The distribution of radioactivity into various phospholipids determined by thin-layer chromatography was similar for the two cell types. When labeled glucose was used as a substrate to measure incorporation primarily into the glycerol backbone of the cell lipids, neutrophils incorporated more radioactivity into total lipids and triglycerides than lymphocytes. These results indicate that neutrophils take up much more fatty acid than lymphocytes primarily because they synthesize much larger quantities of triglycerides, a storage form. Since cellular triglycerides may act as a source of fatty acid for lecithin synthesis during phagocytosis, the greater rate of fatty acid incorporation in the neutrophil may reflect a metabolic pattern that permits efficient phagocytosis.


Oxidation of epinephrine by a cell-free system from human granulocytes. Homogenates of normal human granulocytes were found to catalyze the oxidation of epinephrine to adrenochrome. This reaction was abolished by superoxide dismutase and catalase, but not by albumin or boiled dismutase, indicating that epinephrine oxidation was dependent on O2- AND H2O2. Elimination experiments to identify the electron donor for O2- production showed that the reaction was not inhibited by gel filtration of the homogenate or by removal of glucose, sucrose, or phosphate from the reaction mixture, raising the possibility that epinephrine itself was the reducing agent for the production of O2-. However, we could obtain no evidence for the direct involvement of epinephrine in this step. To explain our observations, we have proposed a mechanism of adrenochrome production involving a radical chain process with one or more enzyme-catalyzed steps. Reactants participating in this chain were postulated to be O2-,-OH (produced by the reaction of O2- with H2O2), and various intermediate products of oxidation of epinephrine. An unidentified endogenous constituent was postulated as the agent responsible for the initial conversion of oxygen to O2-.


Prophylactic granulocyte support in experimental septicemia. The purpose of this study was to determine the value of prophylactic granulocyte transfusions in preventing death from sepsis. An intravenous dose of 10(9) Escherichia coli was lethal when given to granulocytopenic rats 6 days following irradiation with 750 rads. Only one of 22 irradiated animals survived the septicemia. Although normal (nonirradiated) animals experienced a transient leukopenia from this dose of organisms, it was less than LD10 for the normal host. There were no deaths in a group of animals receiving irradiation only. A group of 14 irradiated animals was given a single granulocyte transfusion 2 hr before the septic inoculum, and 57% of these animals survived (p less than 0.01). No antibiotic therapy was administered to any of these animals. Irradiated animals who received granulocytes and recovered from sepsis had earlier granulocyte reconstitution than animals irradiated but not given the septic challenge. Platelet reconstitution was the same in both groups. In the rat model, prophylactic granulocyte support of septc animals led to improved survival. It was concluded that granulocyte prophylaxis may be of value in selected patients with transient bone marrow failure who are therefore at high risk from sepsis.


Evaluation of extracorporeal alkylation of red cells as a potential treatment for sickle cell anemia. Nitrogen mustard and nor-nitrogen mustard inhibit sickling, but the concentrations required would be associated with unacceptable toxicity if these agents were administered to patients. Red cells could be treated extracorporeally and infused back into donors, if the alkylating agent could be removed or inactivated, if the treatment per se did not significantly shorten red cell survival, and if viable alkylated lymphocytes could be eliminated from the treated blood. To estimate whether these conditions could be met in a clinical trial, red cells from four dogs were alkylated at 6-wk intervals. No toxic reactions were observed, although not all nor-nitrogen mustard was removed by the washing procedure. Red cell survival was shortened to about half that of control cells, using concentrations of alkylating agent which reduce sickling by 50%. Lymphocytes from treated blood could still exclude trypan blue, but could not be shown to circulate after reinfusion into donor dogs. If alkylating agents are used to treat patients' cells, inhibition of sickling may outweigh the shortening of red cell life span induced by the treatment; blood should probably be irradiated before infusion to avoid administration of alkylated and potentially mutated, but viable, lymphocytes.


Translation of human globin mRNA: globin synthesis in cells containing Hb Leiden. Most structurally abnormal hemoglobins are present in smaller amounts than HbA in the erythrocytes of heterozygous subjects. In the presence of a hemoglobinopathy, alpha and beta globin synthesis remains balanced with equal production of the two types of chains. In reticulocytes of subjects with Hb Leiden (beta 6 or 7 glu leads to 0) there is greater production of alpha than beta globin in vitro (beta/alpha = 0.67), and slightly more beta A is synthesized than beta Leiden (beta A/beta Leiden = 1.28). Differences in specific mRNA content, rates of initiation of chain synthesis, or rates of chain elongation could be responsible for such differential polypeptide synthesis. In the present study, the ribosomal assembly of beta A, beta Leiden, and alpha globin chains was examined in peripheral blood. The translation times of the three chains did not differ significantly (average times: beta A = 65.4 sec, beta Leiden = 70.8 sec, alpha = 53.5 sec). These results indicated that an altered rate of translation was not the source of the anomalous globin synthesis observed in vitro in cells containing Hb Leiden. The experiments suggested that the observed imbalance in alpha/beta production was due to either differential rates of initiation of globin chain synthesis or quantitative differences in the amounts of the specific mRNAs present in the cells.


Lipid membrane peroxidation in beta-thalassemia major. The composition of membrane lipids was studied in 17 splenectomized and eight unsplenectomized patients with beta-thalassemia major and compared to normal controls. The results showed a nearly twofold increase in total cell lipids; a reduction in the percentage, but not the absolute amount of phosphatidylethanolamine, and a corresponding increase in phosphatidylcholine in the lipids; a considerable increase in the percentage of the saturated fatty acid, palmitic acid, and a reciprocal decrease in the polyunsaturated fatty acid, arachidonic acid; a twofold increase in the amount of malonyldialdehyde (MDA) generated after peroxide threat to the RBC when calculated either per gram hemoglobin or per cell; no change in the amount of MDA generated when calculated per microgram of membrane phosphorus at risk per cell; and a considerable decrease in serum alpha-tocopherol (vitamin E) levels. Thalassemic erythrocytes contain more lipid per cell which is susceptible to peroxidation. In addition, the distribution of fatty acids in these cells suggests that autooxidation of that lipid may have occurred. Autooxidation may be initiated by free radicals, which are constantly formed in the normal red cell, and may be especially prevalent when unstable hemoglobins are present. The low MCHC or some other intracellular defect of thalassemic cells may allow such potent oxidants to find their way to the cell membrane. Vitamin E, a biologic antioxidant is decreased in these patients, and clinical supplementation may be indicated to prevent some of the membrane damage in thalassemia.


Platelet to leukocyte adherence phenomena associated with thrombocytopenia. Two patients developed thrombocytopenia associated with an in vitro platelet to leukocyte adherence phenomenon (PLAP). In one patient, whole serum, intact plasma, and the IgG fraction of the serum could induce the PLAP of normal platelets in normal whole blood or buffy coat preparations. Passage of serum over a Sepharose column coupled with antihuman IgG resulted in the loss of all the PLAP activity. Activity could not be recovered from the whole serum or the IgG fraction of serum of the second patient; however, the PLAP was transferred to her newborn infant. In both patients, an unusual pulmonary illness accompanied the PLAP and thrombocytopenia.


[Leukocyte and erythrocyte interaction with collagen in vitro: scanning electron microscopy study]. Scanning microscopic investigations show the interaction of Leukocytes and Erythrocytes with fibrillar and aggregating type I and type III collagens in vitro. Leukocytes, in the presence of collagen, form loose aggregates within a minute and these aggregates, after 15 to 30 minutes, coalesce and become compact. The close association of the fibrillar collagens to the leukocyte surfaces is shown. Fibrillar collagen and collagen in solution with erythrocytes form only loose aggregates. Qualitative differences between the various collagen preparations were not found. The pathogenetic implications of these observations are briefly discussed.


Heterogeneity of human cell membrane sialoglycoproteins. Discontinuous sodium dodecysulfate polyacrylamide gel electrophoresis (disc SDS-PAGE) followed by periodic acid/Schiff staining reveals the presence of six sialoglycoprotein bands in human red cell membranes or glycoprotein preparations therefrom. In agreement with previous investigations it is shown that PAS-1 and PAS-2 (mol. weight 37 000) are different forms of the same molecule (MN glycoprotein). Using separation of glycoproteins by the system of Weber and Osborn and reelectrophoresis of gel slices by disc SDS-PAGE it is demonstrated that the minor component C (mol. weight 41 000) represents the dimeric form of PAS-3 (Ss glycoprotein). Band B corresponds to an aggregate of PAS-3 and PAS-2 and/or the trimer of PAS-3 with possible differences between extracted glycoproteins and those present in the membrane. The minor component D (mol. weight 35 000) is, as far as could be elucidated, not involved in aggregation phenomena. Some technical problems of glycoprotein fractionation by SDS-PAGE and the remarkable effect of phosphate buffers on the glycoprotein pattern are discussed.


Aquatic insects as biological monitors of heavy metal pollution. A mayfly, Ephemerella grandis, and a stonefly, Pteronarcys californica, were exposed to lead, zinc, copper, and silver to determine the acute metal toxicities. The insects tested were found to be more tolerant of the heavy metals than most fish. They concentrated the metals in relative proportion to the occurrence of the metals in the stream by some predictable, reproducible factor. These data, together with field tests, indicate aquatic insects may serve as effective biological monitors of heavy metal pollution where fish-kills are involved.


A rapid and sensitive method for gas chromatographic analysis of the selective piscicide, "Squaxon". "Squaxon" (1,1'methylenedi- 2 napthol; bis (2 hydroxy-1- naphthyl) methane) was discovered by MacPhee and Ruelle (1968, 1969) to exhibit piscicidal properties that are highly species specific. The chemical is lethal to the Northern (Ptychocheilus oregonensis) and the Umpqua (P. umpquae) squawfish, freshwater cyprinids common to the Pacific Northwest, at water treatment concentrations of less than 100 parts per billion (ppb). Other species of fish, including the more desirable salmonids with which the squawfish competes ecologically, are unaffected until this dosage has been increased severalfold. Because squawfish are widely regarded as undesirable for food or sporting purposes, and because competition from squawfish has severely depleted salmonid populations in some areas (Thompson, 1959; Jeppson and Platts, 1959) the potential use of squaxon for fisheries improvement is quite obvious. Squaxon is currently being tested for this purpose on an experimental basis in selected areas in Idaho, Oregon, and Washington, pending federal clearance for more widespread application.


Effect of methylmercury on humoral immune responses in mice under conditions simulated to practical situations. A suppression and delay in reaching the peak of primary humoral response in mice was noted when relatively large dosage of methylmercury was administered in a short time period, suggesting the interference with the initial multiplications of antibody producing cells. On the other hand, subchronic administration of low levels of methylmercury in diet (0.5 and 5ppm) caused no definite suppression on either primary or secondary responses, though they tended to be depressed.


Teratogenic studies of fenitrothion on white leghorn chick embryos. Teratogenic studies of fenitrothion, an organophosphorus insecticide were conducted on White Leghorn chick embryos. Fenitrothion injections of 5 to 30% concentration in 0.1 ml volumes into the egg yolk space during 4th to 12th day of incubation were lethal to the embryos and the concentration of 0.1, 0.5, and 1.0% resulted in 40, 35 and 30% hatch, respectively. The chicks showed visible abnormalities such as dwarfism, curled toe, leg weakness and abnormal gait. Fenitrothion injections were comparatively less toxic during the later stages of embryonic development (8th to 12th day of incubation). The growth rate of chicks hatched from fenitrothion treated eggs was reduced as compared to the control chicks (distilled water treated).


Responses of neurones in the cerebral cortex and caudate nucleus to amantadine, amphetamine and dopamine. 1. Dopamine amantadine and amphetamine have been applied directly by microiontophoresis to single neurones in the caudate nucleus and cerebral cortex of rats anaesthetized with urethane. 2. The predominant response to all three agents was a depression of neuronal firing rate. The responses to dopamine and amantadine could be antagonized by the dopamine receptor blocking agent, chlorpromazine. 3. Amantadine did not cause any potentiation of dopamine responses, suggesting that inhibition of amine uptake was not responsible for its effects. 4. The responses of pyramidal tract cells in the cerebral cortex to dopamine, amphetamine and amantadine were compared in control groups of rats and rats pretreated with reserpine (10 mg/kg i.p.) or alpha-methyl-p-tyrosine methyl ester (200 mg/kg i.p.). The reduction of cortical catecholamine concentrations was confirmed by a direct fluorimetric assay method. 5. Responses to dopamine were unaltered in the amine-depleted animals compared with controls. Responses to amantadine and amphetamine were reduced but not abolished. 6. It is concluded that amantadine acts partly by releasing catecholamines from neuronal stores. The residual responses to amantadine and amphetamine may be the result of a direct postsynaptic receptor stimulation.


Metabolism of phenylethylamine in rat isolated perfused lung: evidence for monoamine oxidase 'type B' in lung. Phenylethylamine is inactivated in a single passage through rat lung tissue by a process of uptake and deamination by a monoamine oxidase 'type B'. This enzyme is particularly susceptible to inhibition by deprenil and less sensitive to clorgyline. The monoamine oxidase of the lung, like that of other rat tissues, can be differentiated into 'type A' and 'type B' which appear to operate independently in the organized tissue.


A note on the effect of dithiothreitol (DTT) on the depolarization of isolated sympathetic ganglia by carbachol and bromo-acetylcholine. The S-S reducing agent, dithiothreitol (DTT) altered the properties of nicotinic receptors in rat superior cervical ganglia such that (i) carbachol became less active as a depolarizing agent and (ii) bromo-acetylcholine produced an irreversible depolarization. The latter was temporarily annulled by hexamethonium (which retained antagonist properties), but returned when hexamethonium was removed. It is concluded that ganglionic nicotinic receptors might be quite similar to those for monoquaternary agonists in leech dorsal muscle.


Antioxotremorine action of propranolol.

Antioxotremorine action of propranolol. 1. The influence of propranolol on the neuromuscular, tremor-producing and muscarinic effects of oxotremorine was examined. 2. In the isolated rat phrenic nerve-diaphragm preparation the neuromuscular blocking effect of oxotremorine was inhibited by propranolol in a dose-dependent manner. 3. Propranolol intensified the paralytic effect of tubocurarine in the rat diaphragm and prevented antagonism of tubocurarine paralysis by tetraethylammonium. 4. Propranolol was devoid of any curare-like effect in the isolated rectus abdominis muscle of the frog. 5. Vasodepressor responses to oxotremorine in rats and spasmogenic responses to oxotremorine in guinea-pig ileum were not antagonized by propranolol. 6. A dose-dependent antagonism of oxotremorine-induced tremor in mice was observed after pretreatment with propranolol and it is suggested that this effect is due to an antagonism of a presynaptic effect of oxotremorine at skeletal neuromuscular junctions.


Pressor effects of tryptamine analogues. 1. Methylation of tryptamine in the 1-position had little effect on the potency of the drug as a pressor agent in the intact anaesthetized rat. 2. In contrast, substitution of a benzo[b]thiophene ring system for the indole ring decreased the pressor activity. 3. Pretreatment of the animals with reserpine reduced the pressor effect of tryptamine and its benzo[b]thiophene analogue while increasing the effect of the 1-methylindole analogue. 4. Pretreatment with phenoxybenzamine reduced the pressor effect of all three compounds.


Effects of 5,7-dihydroxytryptamine on an identified 5-hydroxytryptamine-containing neurone in the central nervous sytem of the snail Helix pomatia. 1. The effect of 5,7-dihydroxytryptamine (5,7-DHT) on an identified 5-hydroxytryptamine (5-HT)-containing neurone in the CNS of the snail was studied by histochemical, biochemical and electrophysiological methods. 2. Low concentrations of 5,7-DHT decreased the endogenous 5-HT content of the neurone without affecting the amino acids, while relatively large amounts of the drug proportionately lowered 5-HT and in addition slightly decreased the tryptophan and methionine content of the cell. 3. 5,7-DHT blocked the uptake of [3H]-5-HT into the neurone; the close analogue 5,6-DHT was more potent. 4. As well as slightly influencing the accumulation of [3H]-tryptophan by the neurone 5,7-DHT inhibited the metabolism of this amino acid to form 5-HT, probably by affecting the enzyme tryptophan-hydroxylase. 5. 5,7-DHT produced a postsynaptic blockade of transmission from the neurone by blocking the 5-HT receptors of the follower neurones. This effect appeared to be specific for 5-HT receptors. 6. The data support the idea that 5,7-DHT is neurotoxic for indoleamine-containing neurones.


Bioassay of histamine in the presence of prostaglandins. 1. An Amberlite XAD-2 column in a heated (37 degrees C) jacket was incorporated in between two banks of bioassay organs superfused with Krebs bicarbonate solution in cascade. The column removed prostaglandins, E1, E2 and F2alpha and also rabbit aorta contracting substance (RCS) and possibly slow reacting substance of anaphylaxis (SRS-A). 2. The column gave free passage to histamine in concentrations up to 3000 ng/ml. The method described improved the accuracy of histamine bioassay in the.presence of prostaglandins.


Tolerance to the cardiovascular effects of delta9-tetrahydrocannabinol in the rat. 1. Daily intraperitoneal injections of delta9-tetrahydrocannabinol (delta9-THC, 10 mg/kg) resulted in tolerance to the effects of the cannabinoid on body weight and body temperature within 1-2 weeks of treatment. 2. Tolerance failed to develop to the suppression of spontaneous motor activity produced by delta9-THC during 28 days of treatment with the cannabinoid (10 mg/kg, i.p. per day). 3. Following treatment with vehicle for 28 days, intravenous administration of delta9-THC in anaesthetized rats produced a transient pressor response followed by a sustained hypotension and bradycardia. 4. Tolerance to the hypotensive and negative chronotropic responses to intravenous delta9-THC was readily apparent in animals which had received daily intraperitoneal injections of delta9-THC (10 mg/kg) for 28 days. 5. Tolerance failed to develop to the pressor actions of intravenous delta9-THC after 28 days of preptreatment. 6. There was no difference in the pressor response to intravenous noradrenaline in vehicle-treated animals (1.0 ml/kg, i.p., per day for 28 days) and delta9-THC-treated animals (10 mg/kg, i.p., per day for 28 days).


The effect of lithium chloride on one-trial passive avoidance learning in rats. 1 Expression of a one-trial passive avoidance learning response in rats was examined following injections of lithium chloride or sodium chloride before and after initial training and before the first day of testing. Five tests were given at daily intervals, 24 h after training being the time of the first test. 2. Lithium given before the first day of testing impaired response expression on the first and all subsequent days of testing; the rate of extinction was unaffected. 3. Given both before and immediately after initial training, lithium impaired response expression on the first day of testing but slowed down the subsequent rate of extinction, leading eventually to improved performance on the fifth day, as compared with placebo-treated control subjects. 4. The results are interpreted in the light of the hypothesis that lithium impaired the central processing of sensory information.


Antagonism of gamma-aminobutyric acid and glycine by convulsants in the cuneate nucleus of cat. 1. Some convulsant substances have been applied to single neurones in the cat cuneate nucleus by microiontophoresis. Numerical values were derived for the effectiveness and selectivity of the substances as antagonists of gamma-aminobutyric acid (GABA) and glycine. 2. (+)-Bicuculline methochloride was the most effective GABA antagonist and it also excited many neurones. It antagonized GABA in 93% of experiments but also antagonized glycine in 41% of experiments. In most experiments the antagonism of GABA was greater than the antagonism of glycine resulting in an overall selective antagonism of GABA that was statistically significant. Nevertheless, in only about one quarter of the individual experiments was the GABA antagonism substantial and the selectivity clearcut. 3. (+)-Bicuculline and picrotoxin were less easily applied to neurones by microiontophoresis and were found to antagonize GABA in 30% and 35% of experiments, respectively. They also antagonized glycine in 25% and 30% of experiments, respectively. Overall, neither substance could be shown to be selective, statistically, although in the few individual experiments where the GABA antagonism was substantial the antagonism was clearly selective. 4. (+)-Tubocurarine antagonized GABA in 59% and glycine in 32% of experiments and it also excited many neurones. Penicillin antagonized GABA in 33% of experiments without antagonizing glycine. Neither antagonist caused any substantial antagonisms of GABA and neither showed significant selectivity overall. (-)-Bicuculline methochloride, leptazol and bemegride antagonized GABA or glycine in less than 10% of experiments, although (-)-bicuculline methochloride excited most neurones. 5. Strychnine antagonized glycine in every experiment while antagonizing GABA in only 5% of experiments. In each individual experiment the antagonism of glycine was substantial and clearly selective, resulting in a statistically significant selectivity overall. 6. It is concluded that the selective glycine antagonist strychnine is considerably better than the presently available GABA antagonists for distinguishing between responses to GABA and glycine, when the antagonists are applied by microiontophoresis.


Rat submandibular gland kallikreins: purification and cellular localization. 1 Four submandibular gland kallikreins (E.C.3.4.21.8) were isolated by chromatography on DEAE-Sephadex A-50 and hydroxyapatite, followed by gel filtration and electrofocusing. The pI values were 3.87, 3.96, 4.07 and 4.16, and a common molecular weight of 34,000 was found. 2 The kallikreins were localized by direct immunofluorescence with an antibody to rat urinary kallikrein, to the granular tubules, striated duct cells and some main duct cells in the submandibular gland, and to striated duct cells in the sublingual gland. Kallikrein was not found in acini and stroma. 3 Several non-kallikrein esterases present in the submandibular gland reacted with the antibody to rat urinary kallikrein. The antibody was made monospecific for kallikrein by absorption with the crossreacting esterases. 4 We suggest that kallikrein is produced in striated duct cells. Granular tubules, which are differentiated from striated duct cells, have preserved the ability to produce kallikrein. These cells also store large quantities of kallikrein.


Shape change and aggregation of blood platelets: interaction between the effects of adenosine and diphosphate, 5-hydroxytryptamine and adrenaline. 1 The interaction of effects between 5-hydroxytryptamine (5-HT) and adenosine diphosphate (ADP) on human or rabbit platelets was investigated in vitro. The initial platelet shape change and their aggregation were measured in stirred, citrated platelet-rich plasma (PRP) at 37 degrees C by recording the rate and extent of changes in light scattering and light transmission. 2 Both the velocity and extent of aggregation and the velocity and extent of the rapid morphological change caused by ADP were enhanced by simultaneous addition of 5-HT. Methysergide but not imipramine inhibited the 5-HT effects. 3 Platelets were made refractory to the aggregating and shape changing effect of either ADP or 5-HT by repeated aggregation with the particular agent; platelets made refractory to ADP retained their responsiveness to 5-HT and platelets made refractory to 5-HT responded to ADP. Platelets pre-incubated for 3-10 min with 5-HT without aggregation showed greatly reduced aggregation on subsequent addition of ADP. Methysergide inhibited all the effects of 5-HT whilst imipramine was inactive. 4 When the shape change or aggregation of platelets induced by ADP was submaximal, addition of 5-HT increased it further. Pre-incubation of PRP with 5-HT before the addition of ADP resulted in failure of the secondary induction of aggregation or shape change by 5-HT. The secondary induction by 5-HT also did not occur in the presence of methysergide; imipramine had no inhibitory effect. Similar secondary induction of aggregation was shown by adrenaline injected during aggregation by ADP; the adrenaline effect was removed by phentolamine but not by propranolol. 5 Our results show that the initial change in shape of platelets and their aggregation can be induced by ADP or 5-HT in specific manner. The interaction of the effect of these substances on platelets can result in either increase in platelet sensitivity or, under certain conditions, decrease in platelet responsiveness. The increase or depression of platelet reactivity appears to be a highly specific effect and is probably mediated at specific receptors involved with platelet activation.


Cardiovascular effects of diethylcarbamazine citrate. 1 The cardiovascular effects of the anthelmintic drug diethylcarbamazine citrate (DECC) were examined in cats anaesthetized with pentobarbitone. There were two quite distinct haemodynamic responses, an initial transient hypotension (occurring within 10 s of an intravenous injection) and a pronounced secondary hypertension which reached a peak 30-60 s after the injection. 2 Within 10 s of an intravenous injection of DECC (2.5 to 10 mg/kg) there was hypotension, bradycardia and there were reductions in left ventricular and carotid artery dP/dt max. These effects were most pronounced following injections into the pulmonary artery; they were not observed after bilateral vagotomy or after injections into the lumen of the left ventricle. It is suggested that DECC, like nicotine, stimulates vagal receptors in the pulmonary vascular bed. 3 The secondary phase was characterized by marked systemic and pulmonary hypertension, by contractions of the nictitating membrane and by increases in left ventricular dP/dt (at fixed isovolumic pressures), in cardiac output and in myocardial blood flow. All these effects were prevented, or markedly reduced, following the administration of hexamethonium or bethanidine and the pressor response was prevented by phentolamine. It is concluded that, in doses similar to those used in therapeutics, DECC stimulates sympathetic ganglia and releases noradrenaline. The relevance of this finding to the reported side effects of the drug are discussed. 4 DECC (5 or 10 mg/kg) significantly inhibited prostaglandin F2alpha-induced increases in peak inspiratory intra-tracheal pressure without modifying its pulmonary hypertensive effect. The possible relevance of this finding to the use of DECC in asthma is discussed.


Inflammatory effects of prostaglandin D2 in rat and human skin. 1 Intradermal injection of prostaglandin (PG) D1 and D2 in the human forearm produced a long-lasting dose-related erythema. When compared with prostaglandin E1 or E2 the order of potency for erythema production was PGE1 greater than PGE2 greater than PGD2 greater than PGD1. 2 In rat skin, prostaglandin D2 but not D1 caused an increase in vascular permeability as quantitated by the Evans blue method and the 125I-albumin extravasation technique. Prostaglandin E2 was 3-5 times more potent than prostaglandin D2. 3 Prostaglandin D2 (10 ng) potentiated the increase in vascular permeability in rat skin produced by histamine, but not that produced by bradykinin. 4 Prostaglandin D2 (10, 20 and 50 ng) did not elicit oedema or hyperalgesia in the rat paw oedema test, but potentiated carrageenan-induced oedema; hyperalgesia was potentiated by doses of 100 ng and above.


Homicide in the West of Scotland.

Homicide in the West of Scotland. Between 1953 and 1974 the author made psychiatric examinations for the prosecution of 400 persons, 367 males and 33 females, accused of the murders of 307 victims, 194 males and 113 females. The 367 males were accused of 273 murders, 172 male and 101 female victims, and the 33 females were accused of 34 murders, 22 male and 13 females victims. The salient features amongst the accused were maleness, youthfulness, the causal importance of alcohol, the rarity of suicide after murder an the high percentage of psychiatrically normal persons: in these last two respects the picture differed from that reported in England and Wales. The normality of these Scottish accused was further shown by the finding that in the decade 1965 to 1974 no material psychiatric abnormality was seen in 90 per cent of the males examined.


Cross-validation of a predictive scale for subsequent suicidal behaviour in an Italian sample. A six-point prodictive scale for parasuicide repetition developed by Buglass and Horton (1974a) was tested on a group of patients admitted for parasuicide to a psychiatric ward of one of the city hospitals of Verona. The scale gave a range of probability of repetition within 12 months of 15 per cent at a score of o up to 45-5 per cent at the scores 3, 4, 5 and 6. Moreover the scale discriminated significantly between repeaters and non-repeaters. Items significantly associated with repetition in the Italian sample, which are not represented by the six-point scale were: previous parasuicide not admitted to hospital, violence received, alcohol taken at time of act, less than one year at the present address.


The use of autocorrelation analysis in the longitudinal study of mood patterns in depressed patients. The statistical method of autocorrelation, commonly used in econometrics and engineering, was applied to the daily mood scores of ten depressive hospital in-patients. The analyses made possible the quantification of two aspects of the longitudinal course of individual patients' psychopathology, the degree of day-to-day stability and the degree of periodicity in mood. Quantification of the degree of day-to-day mood stability yielded wide variations between patients and suggested that patients might be usefully categorized in terms of this characteristic. Mood stability during periods of severe depression was found to be less pronounced than during periods of relatively moderate depression. Furthermore, the existence of 'mini-cycles', cyclical fluctuations in mood of one to two weeks' duration occurring during the course of depressive episodes, was demonstrated in three cases.


Serum creatine phosphokinase in acute psychosis. Fifty-four patients suffering from a variety of psychotic states were graded by their degree of psychomotor activity. Serum creatine phosphokinase (cpk) levels were found to be related to the degree of psychomotor activity, irrespective of the diagnostic category. Retarded and withdrawn patients had normal serum CPK, but on their return to normal psychomotor activity the CPK levels tended to rise transiently. It appears that unphysiological motor activity has a more direct relationship to the rise of serum CPK than motor activity per se.


Impotence: prognosis (a controlled study). Sixty-five patients primarily referred for erectile impotence were investigated and treated in a psychiatric out-patient department. Information was obtained from patients and wherever possible from their partners. Subjects were treated either with chemotherapy or with a modified form of Masters and Johnson's technique. A controlled group were not given any specific treatment. Results indicated that neither chemotherapy or behaviour modification (modified Masters and Johnson's technique) were in any way superior to no treatment. The prognosis was related to the clinical features of the subjects rather than to the form of treatment. Subjects in whom impotence was caused by a specific psychological or physical trauma showed a much better prognosis than those who had an insidious decline in sexual potency without any discernible psychological or physical factors. The decline in these latter subjects with a very poor prognosis was possibly due to inherent physiological factors.


Cognitive reduction in presenile dementia related to regional abnormalities of the cerebral blood flow. Fifty-five patients with presenile dementia were examined. There were 28 women and 27 men, and the mean age was 59 and 56 years respectively at the time of the study. A large series of psychometric tests was used, and with the aid of age-matched non-demented controls five significantly different cognitive reduction groups could be identified. In the demented patients the regional cerebral blood flow (rCBF) was determined with an eight-detector or 32-detector equipment. There was a rough proportionality between the cognitive reduction and a decrease of the cerebral blood flow (especially the flow in the grey matter). In addition, certain regional flow abnormalities correlated with specific cognitive functions in a manner resembling the cognitive defects found in focal brain lesions in the same region. Thus, patients who showed only memory disturbances demonstrated a focal flow reduction in the temporal region. More severely affected patients, with reduction of verbal abilities and signs of agnosia, showed very low flows in occipito-temporo-parietal parts of the hemisphere. The results offer a principal confirmation of the dynamic field theory concerning the functional organization of the cerebral cortex.


Stereotactic limbic leucotomy--a follow-up at 16 months. Sixty-six patients were assessed clinically, psychologically and physiologically before operation, at six weeks and at a mean of 16 months following stereotactic limbic leucotomy. Seventy-three per cent were clinically improved at six weeks and 76 per cent at 16 months. In obsessional neurosis, 89 per cent of patients showed definite clinical improvement at 16 months; in chronic anxiety, 66 per cent were improved; in depression, 78 per cent; and in the small number of schizophrenics treated the improvement rate was over 80 per cent. Self-assessment and observer-assessment questionaires and scales measuring Depression, Anxiety, Neuroticism, Hysterical symptoms and Obsessional symptoms and traits all showed highly significant reductions of mean scores at 16 months. There was no fall-off in intelligence, and adverse effects were minimal. Limbic leucotomy, with its enhanced accuracy and safety, compares very favourably with similarly assessed, more extensive 'free-hand' procedures, and in obsessional neurosis and chronic anxiety the results are superior.


Electroconvulsive therapy in Denmark.

Electroconvulsive therapy in Denmark. During the fiscal year 1 April 1972 to 31 March 1973, 22,210 ECT treatments in 3,438 series were given in Denmark (6-46 treatments per series). Indications for treatment were: endogenous depression, acute delirium, mania, hysterical psychosis, reactive depression and schizophrenia. Unilateral ECT was used in more than half of the departments concerned. Two treatments were given weekly. The types of apparatus and anaesthesia techniques used are described. One death, which had questionable relation to the ECT, was reported, and other complications were few and mild. The advantages of ECT compared to tricyclic antidepressants are described, including the higher percentage of remissions or improvements in the treatment of endogenous depressions (about 80 per cent for ECT compared to about 60 per cent for tricyclic antidepressants). Little risk was found in out-patient administration of ECT. With present techniques and unilateral placement of electrodes out-patient ECT may be recommended for wider use than before.


Validity and clinical utility of the grid test of schizophrenic thought disorder. It is suggested that a clearer distinction should be made between the statistical validity and the clinical utility of the Grid Test of schizophrenic thought disorder. The results of three published studies are examined, and in each case the Grid Test is found to have appreciable statistical validity in terms of correlations between grid predictions and clinical judgements of thought disorder. Two criteria are proposed for assessing the usefulness of the Grid Test as a diagnostic instrument, and from an examination of the results of three published studies it is concluded that, despite its statistical validity, the test, at least in its present form, has no appreciable clinical utility.


Plasma tryptophan concentration in depressive illness and mania. Total and free plasma trytophan levels were measured in depressive and manic patients before and after recovery. No change was found in total or free plasma trytophan concentration on recovery from depressive illness. Free plasma tryptophan levels were higher in recovered manics than in active manics, and a group of four manic patients tested before and after recovery showed a significant increase in free plasma tryptophan concentration on recovery.


The personality and mental health of flat dwellers. The proportion of persons with neurotic personalities in flats was not significantly greater than that in houses. Extraversion was not correlated with psychiatric illness or with the tendency to consult a doctor. Flat dwelling, but not house dwelling, was sufficient stress for neurotic personalities to cause, among them, an increase in clinical psychiatric illness. The resulting increase in the overall level of psychiatric illness of all flat dwellers was too small to be significantly greater than that of all house dwellers.


Late effects of early dependency need deprivation: the meal ticket syndrome. A psychiatric condition disabling to persons in the fifth and sixth decades is described. Approximately 51 per cent of nearly 1,000 Social Security Disability applicants sampled presented a wide variety of somatic and psychological complaints, but no severe psychiatric disorder. This group is characterized by inability to continue gainful employment. Commencement of full-time employment before age 16 years (59 per cent) and level of education were the only significant differences between this group and psychotic applicants; another 33 per cent began full-time work before age 20 years. 88-5 per cent of the families of these persons remained intact until after they began work. Apparently, being thrust into the responsibilities of adulthood earlier than their peers contributed to the early disability.


Observations on the evolution of the hysterical symptomatology. A retrospective study of the records of 17,571 psychiatric patients who attended the out-patients department of Eginition Hospital in Athens during three two-year periods (1948-50, 1958-60 and 1969-71) revealed a statistically significant decrease in the frequency of patients diagnosed as suffering from hysteria, a statistically significant decrease in the relative frequency of patients with hysterical fits and with mental conversion symptoms, and a statistically significant increase in the relative frequency of patients with mixed conversion symptoms. The findings confirm the notion that hysteria is still a 'woman's disease', although a statistically significant increase in male participation was noted. The significance of the above findings for the understanding of certain aspects of hysteria is discussed.


The SCL-90 and the MMPI: a step in the validation of a new self-report scale. The present investigation was intended principally as a concurrent validation study for a new self-report symptom inventory: the SCL-90. A sample of 209 'symptomatic volunteers' served as subjects and were administered both the SCL-90 and the MMPI prior to participation in clinical therapeutic drug trials. The MMPI was scored for the Wiggins content scales and the Tryon cluster scales in addition to the standard clinical scales. Comparisons of the nine primary symptom dimensions of the SCL-90 with the set of MMPI scales reflected very high convergent validity for the SCL-90. Peak correlations were observed with like constructs on eight of the nine scales, with secondary patterns of correlations showing high interpretative consistency.


Career intentions of senior registrars in general psychiatry. A postal inquiry of all senior registrars in general psychiatry in the United Kingdom gave a nearly 90 per cent response rate. Between a quarter and a fifth of the respondents will not be pursuing general psychiatry at consultant level in this country, most of these opting for a psychiatric specialty. Nearly all the overseas graduates will probably remain in this country. Slightly fewer women than men are aiming for a consultancy in general psychiatry, the rest of the women proposing to switch to one of the specialties. Some of the implications of these findings are discussed, including a proposal for a yearly follow-up of the respondents.


Attitude to psychiatric treatment before suicide in schizophrenia and paranoid psychoses. The purpose of the study was to clarify the attitude of patients with schizophrenia and paranoid psychoses towards hospital personnel and treatment procedures during the two pre-suicidal months. The study was carried out on subjects from south Finland who had committed suicide during a three-year period and had been treated under these diagnoses. The controls included suicides who had received psychiatric treatment for other reasons. A questionnaire was issued to ascertain the opinions of the doctor last in charge of the patient and other personnel. Both groups answered independently, and the opinions given were almost the same. Both groups stated that during the last pre-suicidal months the patients with schizophrenia and paranoid psychoses had shown a more negative or indifferent attitude towards personnel than the controls, and their attitude towards medication had been clearly more negative. Among them there were considerably more patients who had ceased to request support or attention. Thus these patients had developed a degree of despair which manifested itself in a negative attitude towards personnel and treatment.


A comparative study of attentional strategies of schizophrenic and highly creative normal subjects. Frequent references have been made to the similarities between highly creative and psychotic thinking. This study attempts to test the hypothesis that one explanation for such a correspondence lies in the fact that individuals in both these populations habitually employ common attentional strategies which cause them to sample an unusually wide range of available environmental stimuli. A group of highly creative adults and a group of equally intelligent but low creative adults were compared with a group of acute non-paranoid schizophrenic adults on three tests designed to assess attentional and other cognitive styles. The results offer support to the view that both highly creative and schizophrenic individuals habitually sample a wider range of available environmental input than do less creative individuals. In the case of the schizophrenic this involuntary widening of attention tends to have a deleterious effect on performance, while, in contrast, the highly creative individual is more able to successfully process the greater input without this incurring a performance deficit.


Some personality characteristics of patients with anorexia nervosa. Twenty-two female patients with anorexia nervosa were assessed by means of objective personality testing. The EPI, Leyton Obsessional Inventory, Cattell's 16 PF and Raven's Matrices were used for this purpose. The personality profile that emerged was of a highly neurotic and introverted person with moderately severe obsessional features and average intelligence.