Malignant melanoma and oral contraceptive use among women in California. Women who had used oral contraceptives, particularly long-term users, were found to have higher rates of malignant melanoma and of a past history of skin cancer than those who had never used oral contraceptives. This excess was confined to lesions of the lower limb. The association between oral contraceptive use and melanoma was noted in 3 separate sets of data, although it was statistically significant only in one. The possibility that this relationship is indirect because, for example, oral contraceptive users are more likely than never-users to be exposed to sunlight and thus to develop malignant melanoma, cannot be excluded.


Altruism and the practice of medicine.

Altruism and the practice of medicine. Biological and psychological research into the antecedents of altruism has considerable significance for those involved in the teaching or practice of medicine. The evidence available indicates that altruistic behaviour is a universal phenomenon influenced by intra-individual, interpersonal, situational and sociocultural factors. A central theme which emerges is the strikingly ambivalent nature of the altruistic drive. The factors which may facilitate or inhibit altruism in medical students and doctors are discussed. Some ways of ensuring that medical training does not seriously distort altruism are suggested.


Psychotherapy: theory, experience, and personalized actuarial tables. This paper addresses the issue of the role of theory in the actual application of psychotherapeutic operations. Within the present framework, psychotherapeutic effectiveness is seen as an empirical, actuarial process which occurs in an interpersonal setting separate from theoretical considerations. The role of theory is discussed and a rationale for the coexistence of equally 'effective' contradictory theories is presented. Suggestions for future research in the area of behaviour change are made and an argument for the eventual development of a 'therapeutic cookbook' is presented.


Voice analysis for the measurement of anxiety. A recently developed technique for the acoustical analysis of speech is described. Speech is analysed electronically for the presence or absence of a microtremor having a frequency of about 10 Hz. This tremor is said to be attenuated in states of psychological stress. The paper present data supporting the validity of this as a measure of anxiety, using states of both normal and pathological anxiety. An objective scoring system is proposed to overcome some of the problems of unreliability. A number of practical advantages of the voice technique are described.


Some psychological characteristics of patients with anorexia nervosa whose weight has been newly restored. A preliminary study has served to demonstrate that patients with primary anorexia nervosa whose weight has been newly restored to normal, and who are currently involved in individual and family psychotherapy, are significantly characterized by having very low self-esteem, by being highly sensitive to social interactions and by being 'obsessoid'. It is suggested that, in therapy, specific behavioural approaches to these problems may usefully complement other psychotherapeutic endeavours.


Inhibitory effect of high oxygen pressure on potassium- induced activation of pyruvate dehydrogenase and glucose metabolism in rat brain slices. The effects of high oxygen pressure on pyruvate dehydrogenase (pyruvate: lipoate oxidoreductase (decarboxylating and acceptor-acylating), EC 1.2.4.1) activity, tissue concentration of ATP, and CO2 production from glucose were studied in rat brain cortical slices. The increase in pyruvate dehydrogenase activity and the lowering of cellular ATP, occurring during potassium-induced depolarization at 1 atm of oxygen, were reversed by increasing the oxygen pressure to 5 atm. When brain slices were incubated at 1 atm oxygen with [U-14C]glucose, a high potassium medium approximately doubled the production of 14CO2. Oxygen at 5 atm abolished this potassium-dependent increase in 14CO2 production with no significant effect on glucose oxidation in normal Krebs-Ringer phosphate medium. Adding 4 atm helium to 1 atm oxygen did not interfere with the ability of potassium ions to activate pyruvate dehydrogenase, lower ATP, or increase glucose oxidation. The results show that toxic effects of hyperbaric oxygen, not manifest in "resting" tissue, may be revealed during stress such as potassium depolarization. The site of the toxic effects of oxygen is probably the cell membrane where excess oxygen appears to interfere with the action of the sodium pump, calcium transport or other processes stimulated by increased concentrations of extracellular potassium.


Polypeptide composition of purified QH2:cytochrome c oxidoreductase from beef-heart mitochondria. 1. The polypeptide composition of purified QH2: cytochrome c oxidoreductase prepared by three different methods from beef-heart mitochondria has been determined. Polyacrylamide gel electrophoresis in the presence of dodecyl sulphate resolves eight intrinsic polypeptide bands; when, in addition, 8 M urea is present and a more highly cross-linked gel is used, the smallest polypeptide band is resolved into three different bands. 2. The identity of several polypeptide bands has been established by fractionation. The two heaviest polypeptides (bands 1 and 2) represent the so-called core proteins, band 3 the hemoprotein of cytochrome b, band 4 the hemoprotein of cytochrome c1, band 5 and Rieske Fe-S protein, band 6 a polypeptide associated with cytochrome c1 and identified with the so-called oxidation factor, and band 7 a polypeptide peptide associated with cytochrome b. 3. The validity of molecular weight estimate for the polypeptides of the enzyme based on their mobility on dodecyl sulphate gels has been examined. The polypeptides of bands 1, 2 and 3 showed anomalous migration rates. The molecular weights of the other polypeptides have been estimated from their relative mobilities on either dodecyl sulphate gels or 8 M urea-dodecyl sulphate gels as 29 000, 24 000, 12 000, 8000, 6000, 5000 and 4000, respectively. 4. The stoicheiometry of the different polypeptides in the intact complex was determined using separate staining factors for the individual polypeptide band.


Evidence for a double hit process in photosystem II based on fluorescence studies. 1. The amplitudes of the fast (0-20 microseconds) and slow (20 microseconds-2 ms) fluorescence rise induced by a 2 microseconds flash have been measured as a function of the energy of the flash in chloroplasts inhibited by 3(3,4-dichlorophenyl)-1, 1-dimethylurea. The saturation curve for the slow rise shows a characteristic lag which is not observed for the fast fluorescence rise. This lag indicates that Photosystem II centers undergo a double hit process which implies that (a), each photocenter includes two acceptors Q1 and Q2; (B), after the first hit, oxidized chlorophyll Chl+ is reduced by a secondary acceptor Y in a time shor compared to the duration of the flash; (c), after the second hit, Chl+ is reduced by another secondary donor, D. 2. According to Den Haan et al. (1974) Biochim. Biophys. Acta 368, 409-421), hydroxylamine destroys the secondary donor responsible for the fast reduction of Chl+. In the presence of 3 mM hydroxylamine, only the secondary donor D is functional and a flash induses mainly a single hit process. 3. The saturation curves for the fast and the slow rises have been studied in the presence of 3(3,4-dichlorophenyl)-1, 1-dimethylurea for a second actinic flash given 2.5 s after a first saturating one. The large decrease in the half-saturating energy indicates the existence of efficient energy transfer occuring between potosynthetic units. 4. Two alternate hypotheses are discussed (a) in which D is an auxiliary donor and (b) in which D is included in the main electron transfer chain.


Effect of light-adaptation on the photoreaction of bacteriorhodopsin from Halobacterium halobium. Light-induced formation of the 410 nm intermediate was investigated on dark-and light-adapted bacteriorhodopsin. The amplitude of the light-induced absorption increase at 410 nm of the light-adapted bacteriorhodopsin was twice as large as that of the dark-adapted bacteriorhodopsin. The amount of protons released from bacteriorhodopsin in response to illumination was also enhanced by light-adaptation. The degree of the enhancement was independent of the temperature in the dark-adaptation. The relation between these photochemical events and the isomeric configurations of retinal is discussed.


Salt-induced absorbance changes of P-515 in broken chloroplasts. Absorbance changes, caused by adding KCl to a suspension of broken chloroplasts in the presence of a low concentration of MgCl2, have been measured in the wavelength region 460-540 nm. The magnitude of the KCl-induced absorbance changes is shown to be proportional to the logarithm of the KCL concentration gradient initially induced across the thylakoid membrane. The difference spectrum of these absorbance changes is shown to be identical with the spectrum of the light-induced absorbance changes, which has been attributed to an electrochromic shift of p-515. This is interpreted as evidence that under these conditions salt-induced absorbance changes of P-515 occur in response to a membrane diffusion potential. The results indicate that the electrogenic potential across the thylakoid membrane, generated by a single turnover light flash, is in the range between 15 and 35 mV.


The dimerization of protochlorophyll pigments in non-polar solvents. The infrared, visible and nuclear magnetic resonance spectra of protochlorophyll a and vinylprotochlorophyll a in dry non-polar solvents (carbon tetrachloride, chloroform, cyclohexane) are presented and interpreted in terms of dimer interaction. The infrared spectra in the 1600-1800 cm-1 region clearly show the existence of a coordination interaction between the C-9 ketone oxygen function of one molecule and the central magnesium atom of another molecule. Infrared spectra in the OH stretching region (3200-3800 cm-1) provide a valuable test of the water content in the samples. The analysis of the absorption and circular dichroism spectra of protochlorophyll a and vinylprotochlorophyll a in carbon tetrachloride demonstrates the existence of a monomer-dimer equilibrium in the concentration range from 10(-6) to 5.10(-4) M. The dimerization constants are (6 +/-2).10(5)1.M-1 for protochlorophyll a and (4.5 +/-21.10(5) 1.M-1 for vinylprotochlorophyll a at 20 degrees C. The deconvolution of visible spectra in the red region has been performed in order to obtain quantitative information on the dimer structure. Two models involving a parallel or a perpendicular arrangement of the associated molecules are considered. From 1H NMR spectra, it appears that the region of overlap occurs near ring V, in agreement with the interpretation of the infrared spectra.


Excitation energy transfer in the light-harvesting chlorophyll a/b.protein. The "light-harvesting chlorophyll a/b.protein" described by Thornber has been prepared electrophoretically from spinach chloroplasts. The optical properties relevant to energy transfer have been measured in the red region (i.e. 600-700 nm). Measurements of the absorption spectrum, fluorescence excitation spectrum and excitation dependence of the fluorescence emission spectrum of this protein confirm that energy transfer from chlorophyll b to chlorophyll a is highly efficient, as is the case in concentrated chlorophyll solutions and in vivo. The excitiation dependence of the fluorescence polarization shows a minimum polarization of 1.9% at 650 nm which is the absorption maximum of chlorophyll b in the protein and rises steadily to a maximum value of 13.8% at 695 nm, the red edge of the chlorophyll a absorption band. Analysis of these measurements shows that at least two unresolved components must be responsible for the chlorophyll a absorption maximum. Comparison of polarization measurements with those observed in vivo shows that most of the depolarization observed in vivo can take place within a single protein. Circular dichroism measurements show a double structure in the chlorophyll b absorption band which suggest an exciton splitting not resolved in absorption. Analysis of these data yields information about the relative orientation of the So leads to S1 transition moments of the chlorophyll molecules within the protein.


Thermal behavior of HeLa and KB cells in suspension and attached to glass. HeLa S-3 and KB cells were grown in a LKB Batch Microcalorimeter under a variety of nutrient medium conditions amd mixing intervals. These conditions produced rather large apparent endothermic and exothermic responses on mixing that could be correlated with the presence of suspended cells (unattached) as well as cells attached to the glass calorimeter vessel. Cells capable of being resuspended upon mixing of the calorimeter vessel produces first an endothermic followed by an exothermic signal while attached cells produced only an apparent endothermic response. The exothermic response is believed to be associated with increased metabolic heat on suspending the cells followed by partial suppression of the steady state metabolic heat on cell settling. Rates of cell settling correlated well with the rate of decay of the exothermic signal. The rapid appearance of endothermicity on mixing suggests it is associated with rapid events such as binding of nutrients to cell surfaces. The response in the endothermic direction on mixing is discussed in terms of the disruption of mechanisms which tend to exclude nutrients from the surface of the cell.


Electrochemical and spectro-kinetic evidence for an intermediate electron acceptor in photosystem I. Absorption changes accompanying light-induced P-700 formation and its decay in the dark at 15 K in Photosystem-I particles poised at various redox potentials have been examined. In unpoised samples, the light-induced absorption change is practically irreversible. At increasingly negative potentials, an increasing fraction of the absorption change, proportional to the fraction of bound iron-sulfur protein chemically reduced, becomes reversible, and the titration curve has a midpoint potential of --530 mV (vs. normal hydrogen electrode). At --66 mV, the P-700 absorption change is 97% reversible. The total P-700-signal amplitude decreases over the same potential span and levels off at about 43% (to slightly over 50% at a substantially higher excitation intensity). These results provide additional support to previous suggestions of an existence of an intermediate electron acceptor located between the primary donor, P-700, and the more stable primary electron acceptor (P-430 or bound iron-sulfur protein).


Characterization of the low temperature thermoluminescence band Zv in leaf: an explanation for its variable nature. Out of the six thermoluminescence bands reported for a mature leaf, one band (Zv) appearing at the lowest temperatures is dependent on the temperature of illumination. The characteristics of this band in fresh leaf are compared with those is a leaf heated to 60 degrees C for 5 min. It is concluded here that this band, following illumination at temperatures lower than 173 K, is part of Arnold and Azzi's Z band (Arnold, W. and Azzi, J.R. (1971) Photochem. Photobiol. 14, 233--240). However, it is part of peak I when observed subsequent to illumination beyond 173 K. An explanation for the appearance of this band at different temperatures is proposed.


[Enzymatic character and subcellular localization of the transformation reaction of 18 hydroxycorticosterone to aldosterone]. The authors study in vitro the conversion of 18 hydroxycorticosterone into aldosterone in duck adrenal subcellular fractions. The enzymatic nature of this conversion is studied by classical enzymologic tests. All results are in favor of an enzymatic conversion and this enzyme is strictly located in the mitochondrial fraction. Results concerning this localisation are expressed as specific activity and relative specific activity. Preliminary results on further experimental data point out that this conversion depends on the energetic state of mitochondria. Complete electron transfer blokage inhibits this transformation whereas respiratory chain blokage with a NADPH generating system and ATP supplementation does not seem to produce any inhibition. Oligomycine and guanidine stimulation suggest that ATP or its precursors may be involved in this reaction.


[Toxic complex from parrotfish].

[Toxic complex from parrotfish]. Clinical and epidemiological observations suggested that a complex toxic molecule is involved in the parrotfish flesh (Scarus gibbus) poisoning from Gambier Islands. The fat soluble extract obtained from the muscles upon ciguatoxin preparation showed two toxic substances after fractionation by DEAE cellulose column chromatography. The major toxin is different from ciguatoxin judging by its chromatographic behaviour. The other is closely similar to (or identical with) ciguatoxin from the moray eel Gymnothorax javanicus. They were named SG1 for the new toxin and SG2 for the ciguatoxin like compound. Successive filtrations on Sephadex LH-20 of SG1 and SG2 gave respectively a lethality to mice of 0.03 microgram/g and 0.06 microgram/g. SG1, specifically occurs in the muscles of the parrotfish family (scaritoxin) while it is absent from other ciguateric fishes. According to that specificity and the lack of SG1 in S. gibbus liver and gut contents, the origin of scaritoxin is briefly discussed.


[Variation of cell membrane lipid composition by means of lipid transfer proteins. Properties of the protoplast membrane of Micrococcus lysodeikticus after incorporation of phosphatidylcholine]. After incorporation of phosphatidylcholine (PC) into the protoplast membrane of M. lysodeikticus by protein mediated transfer from PC liposomes, the activity of some membrane bound respiratory chain enzymes was studied. It was found that incorporation of PC decreases the rates of oxidation of exogenous substrates (NADH, malate) but the level of endogenous respiration was not changed. Ferricyanidreductase activity of ghosts of M. lysodeikticus was not dependent upon the PC content of protoplasts. PC containing protoplasts showed a higher osmotic stability than unmodified protoplasts. It is concluded that the incorporation of PC into the protoplasts results in resealing, i. e. in the repair of local defects in the protoplast membrane.


[Isolation and identification of protochlorophylls obtained by oxidation of corresponding chlorophylls]. Protochlorophyll with a high yield is isolated under oxidation of chlorophyll a by tetrachloro-o-quinone. A pigment, designated as protochlorophyll b, is isolated by the same way from chlorophyll b. A method of purification of the pigments obtained is worked out, their properties are studied and their structures are identified. The proposed method can be recommended for isolation of protochlorophyll a and b.


[The nature of the rate-limiting step in aniline hydroxylation involving cytochrome P-450 from rat liver microsomes]. The kinetics of aniline hydroxylation with: 1) rat liver microsomes involving NADPH and O2 (System I); 2) hepatic microsomes and tertiary butylhydroperoxide (System II) and 3) microsomes and cumyl hydroperoxide (System III) within 15--37 degrees C has been studied. The reactions were characterized by the values of the aniline oxidation rate constants, k2=v/[E]0, where [E]0 is the initial concentration of cytochrome P--450: k1 2=1,60.10(8) exp (--13400/RT) sec-1., k2 2=1,66.10(9) exp (--14500/RT) sec-1., k3 2=6,83.10(9) exp (--15300/RT) sec-1. The values of delta H* and delta S* were calculated and compared for these three systems. A conclusion is drawn that the act of oxygen insertion into the substrate molecule is the rate-limiting step in the reaction of aniline oxidation for the mentioned system.


[Effect of temperature on the interaction of cytochrome P-450 with a variety of amines]. The interaction of cytochrome P-450 of rat liver microsomes with six amines have been investigated in Tris-HCL buffer pH 7.4 within the temperature range of 20--37 degrees C by the differential spectrophotometry method. Dissociation constants for the amine-cytochrome-P-450 complexes have been determined. The interaction of type I substrate, 1,2,7-trimethyl-decahydroquinolone-4, is characterized by the value of Ks(I)=4.14 exp (--6250/RT) mole/1. A value of Ks(II)=10(-8) exp (+6500/RT) mole/1 has been obtained for type II substrate, monomethylaniline. Association of 1,2,7-trimethyldecahydroquinolone-4 to cytochrome P-450 decreases with temperature, where as with monomethylaniline the reverse tendency is observed. Thermodynamic parameters delta H, delta F and delta S characterising the interaction of amines with cytochrome P-450 are evaluated.


[Proton absorption by chloroplasts in cyclic electron transport catalyzed by photosystem I in anaerobic conditions]. Proton absorption by pea chloroplasts in anaerobic conditions under inhibition of non-cyclic electron transport with diurone is investigated. 2,6-dichlorophenolindophenol (DCPIP) and tetramethyl-p-phenylenediamine (TMPD) are used as cofactors of cyclic electron transport. Proton absorption in the absence of methylviologen is found to take place only in experiments with DCPIP, while in the presence of methylviologen it is observed with both cofactors, being considerably higher is the case of TMDP. In experiments with DCPIP absorbed protons comprise two fractions differing in the rate of the output of particles from tilakoids and in the number of the particles. The presence of these two fractions is suggested to be due to the well-known fact of the presence of two sites of electrone intake into electron transport chain by reduced DCPIP. On the basis of dependency of fraction composition on DCPIP concentration and of the mode of dibromothimoquinone, gramicidin D and antimycin A action on these fractions, it is suggested that protons of "a slow" fraction are capable to participate preferably in the ATP synthesis.


[Effect of phosphorylation on glycolysis in the cells of assimilating millet leaf tissues]. The effect of phosphorylation on glycolysis reactions was studied in respect with the rate of 1-14C-glucose metabolization and the composition of synthesized labelled products in isolated cells of assimilating millet leave tissues incapable to reassimilation of respiratory CO2. Data on oxygen metabolism in mesophyll protoplasts and in cells of parenchymal facing of vascular bundle sheaths in the absence and in the presence of electron acceptors (3,5-dichlorophenolindophenol and methylviologen) show that they retain adenylate pool and energy charge characteristic of photosynthetizing tissues. The glycolysis rate decreased in illuminated cells, which did not remove carbon products from chloroplasts. Analysis of compounds produced from 1-14C-glucose exogenous ADP effect on their ration and the change of adenylate energy charge in the presence of methylviologen demonstrates that the acting factor is a decrease of Pi and ADP concentrations in cytoplasm because of their use chloroplast phosphorylation. It is suggested, that a short-cut chain of glycolysis reactions may take place in intact cells assimilating CO2 in photosynthesis, and the capacity of this chain is determined by the type of carbon metabolism and photorespiration mechanism.


[Polysomal apparatus as a reflection of function interactions between translation and transcription processes during protein synthesis inhibited by cycloheximide]. Distribution of optical density and radioactivity in sucrose density gradient was studied for 14C-RNA and 3H-protein polysomal components isolated from normal rat liver 1, 3, 6 12 and 24 hrs after cycloheximide (CHI) treatment (sublethal dose--0,3 mg/100 g body weight). Soon after the antibiotic injection (1--3 hrs), when protein biosynthesis was strongly inhibited (more than 90%), the total quantity of "heavy" polyribosomes and 14C-mRNA associated with this fraction significantly increased. At the same time the amount of free ribosomes showed a decrease. On the contrary, after 6 hrs the amount of polysomes sharply decreased and that of ribosomes and their subunits was increased. In the middle period and at the end of experiment (12--24 hrs) when protein biosynthesis was continuously restored, the polysomes sedimentation pattern was restored as well. Specific radioactivity of 14-C-rRNA's and 3H-proteins in this fraction was also increased. The restoration of optimal protein biosynthesis level after its inhibition by a single cycloheximide injection (sublethal doses) is thought to be a complex process of consecutive interactions between translation and transcription cell systems.


[Characterization of some membrane-active components of Vespa orientalis venom]. The molecular weight distribution of the components of giant hornet (Vespa orientalis) venom was studied, using gel-filtration on a column with Sephadex G-50. The effects of the venom and its constituent fractions on the permeability and stability of artificial bilayer phospholipid membranes, potassium ions release from the erythrocytes and mitochondrial oxidative phosphorylation parameters, as well as on the activity and stability of polyenzymic systems of the mitochondrial respiratroy chain, were studied. The data obtained suggest that the high molecular weight fractions contain phospholipases, whose activities are much higher than those of presently known venoms. Despite the fact that the hemolytic effect is typical for two low molecular weight fractions, no fractions possessing high activity of bee venom of the melitin type were found.


[Genome structure in higher plants. Reassociation kinetics of DNA from Vicia faba and Vicia sativa]. The work been concerned with a study of the kinetics of reassociation of total DNA and that of the fraction of unique sequences in plants from the Vicia family, i. e. Vicia faba and Vicia sativa. The size of the genome was determined by the kinetics of reassociation of the DNA of the fraction of unique sequences and the amount of DNA per nucleus was determined cytophotometrically. It has been shown that the size of the genome expressed in C(0)t units and the size expressed in gramms are not the same which testifies to the absence of true unique genes in the genome of the species studied. The analysis of the possible methodical errors was carried out. On the basis of the data obtained a suggestion was made of a model of chromosomes organization including 12 units of polynemization for Vicia faba and 4 units for Vicia sativa.


[Study of the carbohydrate component of cathepsin D]. A content of neutral sugars and N-acetyl-glucosamine in homogeneous cathepsin D preparations from a variety of vertebrate organs was determined. A more detailed study of the carbohydrate component was carried out with chicken liver cathepsin D preparation. It was shown that carbohydrates constitute 20% of the molecule of this cathepsin and contain glucosamine (11.6%) and mannose (10%). Removal of the major portion of the carbohydrates by treatment with mixture of glycosidases did not lead to any significant decrease of biological activity. This finding suggests that the carbohydrate component is not essential for the biological activity of the enzyme. Analysis of distribution of carbohydrates in the peptides of the trypsin hydrolyzate of cathepsin D allows conclusion that the enzyme molecule has several carbohydrate chains attached to different sites of the molecule.


[Biosynthesis of mitochondrial protein in rat liver under conditions of vitamin B 1 deficiency following oxythiamine injection]. The incorporation of labelled precursors into mitochondrial proteins of liver under different duration of oxythiamine (antivitamin B1) effect was studied in the whole organism and in a cell-free system. After 24 hrs following the injection, oxythiamine at a dose of 400 mg/kg of body weight increases the mitochondrial protein synthesis in vivo without changing the protein-synthesizing capacity of isolated mitochondria. After 72 hrs following the injection of the same dose of preparation, a sharp increase in the rate of protein label incorporation into the mitochondria was observed. The protein synthesis in mitochondria in the whole body studies also showed an increase. It is assumed that oxythiamine enhances the inductive synthesis of mitochondrial thiamine phosphate-dependent enzymes or activates the syntheses of other enzymic systems, capable of increasing the utilization of alpha-keto acids accumulated under conditions of thiamine deficiency.


[Thiol peptides from the aspartate transaminase of chicken heart cytosol]. Aspartate transaminase from chicken heart cytosol was immobilized covalently on activated thiol-Sepharose and digested with trypsin. After washing, the thiol-containing peptides were eluted with 2-mercaptoethanol and further purified by gel-filtration and paper chromatography. Three pure cysteinyl peptides were isolated. One of them may be represented as Ile-(Asp, Met, Cys, Gly, Leu, Thr2)-Lys; this peptide is identical to the fragment comprizing residues 387--395 in the peptide chain of aspartate transaminase from pig heart cytosol. It thus contains a cysteine residue homologous to Cys-390 of the pig heart enzyme. The second cysteinyl peptide had the following composition and partial sequence: Tyr-Phe-Val-Ser-Glu-Gly-Phe-Glu-Leu-Phe (Cys, Ala, Glu, Ser2, Phe)Lys, which corresponds to the sequence 242--258 of the pig enzyme and thus contains a cysteine residue homologous to Cys-252. The third cysteinyl peptide was similar to the tryptic peptide of the pig enzyme containing Cys-191.


Onset of illness in bipolar manic-depressives and their affectively ill first-degree relatives. Some suggestive data regarding age of onset and the relationship of stress to onset in a group of bipolar manic-depressive patients and their first-degree relatives are presented. Possible explanations of the interesting correlation in age of onset among family members are discussed. Because of a small sample size, the clinical significance of the findings are uncertain, but are presented because of their potential interest to those investigating genetic components of affective illness.


Effect of limb restraints on serum creatine phosphokinase activity in normal volunteers. Increased serum creatine phosphokinase (CPK) activity is sometimes found in acutely psychotic patients. In order to study factors affecting CPK activity, we investigated in normal subjects the effect on serum CPK activity of resistance to being restrained and to struggle against leather limb restraints (LLR) sometimes used for control of assaultive of self-destructive behavior of psychiatric patients. Blood samples were obtained 24 hr and immediately before restraint; and immediately, 6, 24, 48, and 72 hr after restraint. Serum CPK activity increases ranged from 3 to 16 times base line levels for all subjects. These increases exceeded the 95% upper limit of normal. Serum pyruvate kinase (PK) activity also increased significantly. In a second study, five male subjects were passively placed in LLR and then struggled against LLR for 1 hr. Serum CPK activity also increased significantly under these conditions, but less than after being forcibly restrained. Serum PK activity and lactic dehydrogenase activity also increased significantly, but serum aspartate aminotransferase (SGOT) activity did not. Since serum CPK activity is increased well above the normal limits in normal subjects after struggle against LLR, studies of serum CPK activity in psychotic patients must avoid the use of restraints as well as other types of trauma, which may produce serum CPK increases persisting as long as 72 hr.


Changes in the electroencephalogram accompanying the use of stimulant drugs (methylphenidate and dextroamphetamine) in hyperactive children. Fifteen hyperactive boys aged 5.6-10.6 years had their electroencephalograms (EEG) recorded during performance of a simple reaction task while on stimulant medication (methylphenidate or d-amphetamine) and after being free of medication for at least 48 hr. Interval histograms were formed from measurements of the duration of 780 half waves taken from predetermined portions of the EEG'S recorded from the left parietal-occipital derivation for both treatment conditions, and the histograms were subjected to a central-moments analysis. Previous evidence showed that, in normal children, smaller-valued 2nd, 3rd, and 4th central moments were associated with greater maturity. The EEG histograms obtained while the hyperactive children were taking stimulant medication had significantly (p less than 0.005) smaller 2nd, 3rd, and 4th central moments than the histograms of the same children obtained when off medication. Age of the group predicted from the means of the 2nd, 3rd, and 4th central moments of the EEG interval histograms was 91 months when the children were off medication--9 months less than the group's actual mean age. Age predicted in the same way when the children were on medication was 97 months. Findings support the concept of a neurophysiological maturational lag in hyperactivity and suggest that this lag is overcome, in part, by the use of stimulant drugs.


Papaverine effect on postischemic acute renal failure in rats. The effect of papaverine at the time of starting a post-ischemic acute renal failure in rats has been studied. Papaverine administration increases diuresis and reduces serum urea and creatinine levels. The primary role of hemodynamic disorders as responsible for the diminished glomerular filtration rate is supported by the reduced severity of acute renal failure when this vasodilator agent is administered.


Contribution to the early diagnosis of congenital toxoplasmosis. A method based on a single serological test enabling the diagnosis of congenital toxoplasmosis immediately after birth is described. The concentration of anti-toxoplasmosis antibody from the CSF is compared to that of rubeola used as reference. It is thus possible to distinguish between the passive passage of antibodies in the CSF and their in situ synthesis. When concentration of antibody in the CSF is higher for toxoplasmosis than for rubeola, the existence of a congenital infection of toxoplasmosis can be suggested.


An assay for serum cytotoxicity against erythroid precursor cells in pure red cell aplasia. Several reports have indicated that a circulating serum inhibitor (antibody) is involved in the pathogenesis of acquired pure red cell aplasia (PRCA). In the present study, the pathophysiologic significance of this inhibitor was assessed according to the status of erythroid progenitor cells in the bone marrow. So far, direct proof for the antibody acting against erythroid stemcells was lacking. Employing an "in vitro" assay, erythroid colony forming cell (CFU-e) numbers in PRCA marrow were quantified and the cytotoxic effect of PRCA serum on CFU-e was investigated. It was revealed that the CFU-e population size in the marrow of PRCA patients was severely reduced; at the same time the relative number of myeloid colony forming cells was normal. The serum was demonstrated to contain a factor cell which was cytotoxic to CFU-e, in the presence of complement. The results indicate that inhibition of erythropoiesis in PRCA is achieved by a complement dependent plasma factor which eliminates or inactivates CFU-e and which constitutes an effective block at the precursor cell level in the differentiation pathway of the erythroid line. The data present a practical assay for measuring cytotoxic factors affecting erythroid stem cells.


Blood platelet and "extra-platelet" serotonin in some myeloproliferative disorders. Most of the blood serotonin is bound to platelets. However, some authors described plasma "free" serotonin; which is normally very low, and might be increased during some diseases. Usual spectrofluorimetric methods and paired by statistical evaluation "extra-platelet" serotonin (not bound to platelets) in the blood of healthy volunteers and patients with myeloproliferative disorders was studied. In these conditions, we cannot be sure of the existence of "extra-platelets" serotonin in the blood of controls and some patients; in others it was present. "Extra-platelet" serotonin is always present in the blood of untreated patients with primary thrombocytosis.


A three dimensional model of the digestion of peptidoglycan by lysozyme. The digestion of single peptidoglycan chains of the recently proposed conformation (Formanek et al., 1974) can be described with the same enzymatic mechanism as proposed by Phillips for a hexasaccharide consisting of alternating N-acetylglucosamine, N-acetylmuramic acid residues (Phillips, 1966). It is shown by model building, that in a peptidoglycan lysozyme complex the peptide chains do not exhibit any sterical hindrance. The digestion of the peptidoglycan sacculus by lysozyme may occur at latice defects of its paracrystalline structure. A slit of about 30 A length and 10--15 A width between peptidoglycan micells may be sufficient for the attachment of lysozyme.


Dynamic stiffness and crossbridge action in muscle. Small sinusoidal vibrations at 300 HZ were applied to frog sartorius muscle to measure the dynamic stiffness (Young's modulus) throughout the course of tetanus. For a peak-to-peak amplitude of 0.4% the dynamic Young's modulus increased from 1.5 X 10(5) Nm-2 in the resting state to 2 X 10(7) Nm-2 in tetanus. After correction for the external connective tissue, the dynamic Young's modulus of the muscle was almost directly proportional to the tension throughout the development of tetanus. The ratio of dynamic Young's modulus to tensile stress thus remained constant (with a value at 300 Hz of approximately 100), consistently with Huxley and Simmon's identification of the crossbridges as the source of both tension and stiffness. For a single crossbridge the ratio of stiffness to tension was 8.2 X 10(7) m-1 at 300 Hz; it is deduced from literature data that the limiting value at high frequencies is about 1.6 X 10(8) m-1. This ratio is interpreted on Harrington's (1971) model to show that crossbridge action can be explained by a helix-coil transition of about 80 out of the 260 residues in each S-2 myosin strand. It is also shown that a helix-coil model can account for the observed rapid relaxation of muscle without invoking any complex behaviour of the crossbridge head.


Structural analysis of denaturant-protein interactions: comparison between the effects of bromoethanol and SDS on denaturation and renaturation of triclinic lysozyme. This paper summarizes our crystallographic studies of the interaction of denaturants with cross-linked triclinic lysozyme. Electron density maps of various bromoethanol-lysozyme complexes are analyzed and compared to those reported earlier for SDS-lysozyme complexes. Despite differences in the chemical nature and size of the two denaturants their mode of interaction with the protein is quite similar, suggesting the existence of a general mechanism for binding of hydrophobic-hydrophilic denaturants to proteins. Our results are consistent with the conclusion that lysozyme consists of two domains connected by a flexible segment and that this segment represents an internal degree of freedom of the protein.


The trajectories of particles suspended in electrolytes under the influence of crossed electric and magnetic fields. Possible explanation of the sensitivity of organism to magnetic fields. We observed that particles, suspended in an electrolyte and brought into crossed magnetic and electric fields of low intensities, will deviate in the central part of the electrophoresis chamber of a standard Zeiss Cytopherometer with a component vertical to both fields. The direction and magnitude, however, were sharply at variance with what would be expected by the action of the Lorentz force (EMF) on the surface of the particles. The magnitude of the deviation depends upon the magnetic and electric field strength, the ion concentration of the suspension medium and the geometry of the chamber. The movement of the particles is due to streaming of the electrolyte which is mainly caused by inhomogeneities of the electric field in the electrophoresis chamber. The magnitude of the effect is high enough to occur physiological conditions. Magneto-electrophoretic streaming might eventually act as a transducer mechanism which could explain the ability of some animals to orientate themselves in the geomagnetic field.


Characterization and mass spectral analysis of some grayanotoxin derivatives. The mass spectra of grayanotoxin III and some of its mono-, di, and tri-ester derivatives are discussed. Some of the physiological responses of this compound class are also presented. The extraction of this material from a natural source is discussed as well as the schemes for ester derivatization and spectral characterization of all compounds studied. High resolution mass spectral analysis and comparison of the mass spectra of similar compounds were used to define possible fragmentation mechanisms.


Mass spectra of some specifically deuterated tryptamines. The mass spectra of the four tryptamine derivatives, N-acetyl-5-methoxytryptamine (melatonin), N-acetyl-5-hydroxytryptamine (N-acetyl-serotonin), N,N-dimethyl-5-hydroxtryptamine (bufotenine) and N,N-dimethyl-5-methoxytryptamine (O-methylbufotenine), with specifically labeled [D4] aminoethyl sidechains have been measured. Comparison of these spectra with those of the unlabeled compounds enable the major fragmentations of the compounds to be defined.


Ring-D fragmentation of cardenolides.

Ring-D fragmentation of cardenolides. The major fragmentation paths typical for the cardenolides system have been elucidated by labelling studies.


Mass spectral characterization of 6-oxo-OGF. The mass spectra of eleven derivatives are presented to provide structural support for the recently discovered prostaglandin, 6-oxo-PGF1alpha, which we have isolated from incubations of arachidonic acid with ram seminal vesicles or released during isolated perfusions of sensitized guinea pig lungs.


In vivo metabolism of cannabinol by the mouse and rat and a comparison with a metabolism of delta 1-tetrahydrocannabinol and cannabidiol. The in vivo liver metabolism of cannabinol has been studied in the mouse and rat by combined gas chromatography and mass spectrometry. Cannabinol glucuronide was the major metabolite of cannabinol in the mouse and was accompanied by relatively large amounts of 7-hydroxycannabinol, cannabinol-7-oic acid and their corresponding glucuronide conjugates. Lower concentrations of glucuronides were found in the rat. Two series of disubstituted metabolites were found containing either a 7-hydroxyl or a 7-carboxylic acid group and a second hydroxyl group in the 1 inch-4 inch positions of the sidechain. These were of low concentration in the mouse but higher in the rat; 1 inch-hydroxy metabolites were particularly abundant in the latter species. Also found in the rat livers were small amounts of sidechain monohydroxy metabolites and larger quantities of 4 inches, 5 inches-bisnorcannabinol-3 inches-oic acid; these were absent in the mouse. The metabolites were identified using the trimethylsilyl (TMS), [2H9] TMS and methyl ester-TMS derivatives, and by reduction of acid metabolites with lithium aluminium deuteride to the corresponding alcohols.


The mass spectral fragmentation of 9alpha-hydroxy steroids and related compounds. The fragmentation processes occurring in various 9alpha-hydroxy steroids upon electron ionization have been studied. The mechanisms proposed for the formation of the prominent ions in these spectra have been confirmed with the aid of deuterium labelling, measurements on metastable ion decompositions, low eV spectra and high resolution mass measurements. The fragmentation of the corresponding 9-oxo-9,10-seco steroids, which shows analogy to that of the 9alpha-hydroxy compounds in many respects, has also been discussed.


On the mapping of chains of first order chemical reactions on random walks. We present the transient solution to a random walk problem which characterizes chemical kinetic processes in which a particular state may have a finite number of internal states. While there are many chemical and physical examples, we introduce the solution through models of biophysical interest.


A mathematical model of periodic processes in membranes (with application to cell cycle regulation). A mathematical model of the regulation of the cell cycle by the plasma membrane is suggested. The model is based on the hypothesis that structural transitions of the cell membrane play an important role in the regulation of cell division. Conditions of transition from the proliferating state to the resting state and back are investigated. Possible qualitative differences between models of the cell cycle of a normal and a tumour cell are pointed out.


Convergent and parallel evolution: a model illustrating selection, phylogeny and phenetic similarity. A model is proposed which considers the structural relationships of body characteristics and their role in a concept wherein the phylogenetic relationship of the organisms under study is interpreted as constituting degrees of convergent or parallel evolution. The model also accounts for the relationships between selection pressures, phylogeny, and phenetic expression. The phenomena of convergent and parallel evolution are based upon the observations of similar characteristics, the geometric concept, magnitude and similarity of selection pressures, and the phylogenetic relationship of the groups in question.


Potentiometric titration behavior of polyaspartic acid prepared by thermal polycondensation. The dissociation behavior of polyaspartic acid prepared by thermal polycondensation was studied by potentiometric titrations at various ionic strengths. From the analysis of the titration curves, the ratio of alpha- and beta-linkaged aspartyl residues was estimated at about 7:3 and the intrinsic dissociation constants of alpha- and beta-carboxyl groups are 3.25 and 4.35, respectively.


Density-dependent limitation of growth and the regulation of cell replication by changes in the triggering level of the cell cycle switch. If the initiation/suppression of cell replication results from the operation of an intracellular switch, then proliferation control can be expected to occur through the modulation of its threshold setting or sensitivity. Assuming the existence of a threshold and the uptake of regulators by an equilibrium process, one can explain various types of dependency of the maximum cell density on the initial level of the regulator (e.g., serum) in the medium. Moreover it becomes theoretically possible to distinguish whether an altered threshold or equilibrium constant is responsible for modified proliferation characteristics. It is pointed out that some published data on transformed cells are more consistent with an altered threshold than the permeability change invoked. Other data suggests that transformation has produced more complex effects. The arguments presented indicate that while some cells may be more susceptible to control via changes in the relevant equilibrium constant, others may respond more markedly to threshold modulation. If control occurs through inhibition of replication, it is possible for the system to exhibit a critical "mass": if this is exceeded (in ways discussed) proliferation could continue indefinitely provided adequate nutrients are available. An oscillator concept of the cell cycle accounts for the existence of a threshold and also permits a general understanding of its modulation by multiple agents. It is concluded that at least some forms of cancer are the result of altered thresholds.


The origin of the protein synthesis mechanism. The origin and development of the protein synthesis mechanism is considered in four successive steps. The genetic code is supposed to be controlled by the relative amount (availability) of various amino acids and nucleotides on the one hand, and utility on each amino acid in the polypeptide. on the other hand. Thus, more simple (inutile) and abundant amino acids tended to correspond to codons which were rich in the less frequent base species, G and C. Features of primitive tRNA in the discrimination of amino acid are discussed. Primitive tRNA is proposed to have a discriminator site for amino acid and, separated from it, an anticodon site for interaction with nucleotides. A hypothetical course of subdivision of various nucleic acid species is proposed. In the scheme, mRNA and ribosomal RNA (rRNA) were derived from more primitive insoluble RNA. DNA appeared in the late, not first, step of the development. Several other aspects of evolutionary development of the whole protein synthesis mechanism, e.g., role of the discriminator site on primitive tRNA, modification and subdivision of code catalogue into a more precise specification of amino acids, and possible primordial interactions between tRNA and tRNA-binding sites on insoluble rRNA, are discussed.


A path analysis of the causal relationships between red cell glycolytic intermediates, ADP and ATP in sickle cell anemia. The statistical relationships among the glycolytic intermediates (GI)) of the Embden-Meyerhof pathway, adenine nucleotides (ANs) and various hematological measures were estimated for 34 sickle cell anemia patients. Heterogeneity in linear and quadratic regressions of hemoglobin and hematocrit, both singly and jointly, on the GI and AN variables implied 1) that any single formula to standardize optical density measures of the GIs and ANs on a per gram hemoglobin or per liter cell water basis would not uniformly remove hemoglobin and hematocrit effects: 2) that ignoring significant hematological effects could bias the estimates of correlation among GIs and ANs; and 3) that hemoglobin and hematocrit measures do not reflect the same source of variability. The correlations among the GIs and ANs, after adjustment for hematological variability, were analyzed by path analysis to determine which of five proposed path models for cause and effect relationships were compatible with the data. AMP had a greater influence on ADP (coefficient of determination (CD) = 23%) than all the GIs together, while G6P and ADP influenced ATP variability the most (CD = 33% and 12%). The contributions of unknown factors to ADP and ATP variability were large for all models (CD = 56--77%) possibly due to stress of sickle cell disease. The path model with AMP and the four GIs (G6P, F6P, FDP, DHAP) influencing ADP variation, and the same GIs and ADP influencing ATP was the model most compatible with the data.


Does the brain actively maintain itself? All living systems have special mechanisms for combatting entropy; however, the brain has dimensions of organized complexity beyong those manifest in the anatomical structure and physiology of the rest of the body. Reasons are given in support of the notion that the brain therefore must have a special, intrinsic "homeostatic" system for its information bearing structures, and, further, that slow electroencephalographic activity has properties which might make it useful for such an order-maintaining function. Recovery from brain damage is hypothesized to be a byproduct of this process, which may involve a cruder sort of information processing than occurs with such functions as perception and learning. Synchronized EEG activity may be adequate to handle this sort of information processing. Speculations are offered about possible mechanics, on the neuronal level, of slow wave participation in plasticity; for example, one such suggestion is based on findings that electrical fields can influence cellular orientation. The methodology of discovering the distribution within the brain of the hypothetical maintenance system is discussed briefly.


Telemetric motor activity in children. A preliminary study. A lightweight telemetric mobility sensing system was used to study the relationship between high levels of motor activity during free-play and school performance. Among the 21 normal children, there was a significant correlation between high ankle motor activity during free-play, poor school achievement, the presence of neurological soft signs, and a poor self-image. Those normals whose free-play ankle activity was above the mean, also had significantly more errors and performed at a significantly lower level on the Bender Visual Motor Gestalt Test than children whose activity was below the mean. This preliminary study suggests that the telemetric mobility sensing system can be easily applied to children to assess clinically relevant components of psychomotor activity.


Precision calibration of patient care equipment as failure predictor. Reliability of patient care equipment could be enhanced if failures could be predicted and repairs made on a routine instead of emergency basis. The paper describes the efforts of the Biomedical Engineering Department at Brookdale Hospital Medical Center to use changes in accuracy of selected parameters as failure predictor. Monthly precision tests of ECG rate computers, strip chart recorders and waveform analysis of defibrillator discharges were used in this experiment. For defibrillators and strip chart records failures could clearly be predicted but the results for ECG rate computers are still inconclusive.


A multichannel telemetry system for long-term in vivo evaluation of implantable materials. Long-term in vivo measurements of the corrosion potentials of various implantable metal materials are performed using an implantable multichannel telemetry system. The data acquisition system has been designed to achieve maximum ease of operation for routine tests in animal applications. A novel signal encoding technique offers advantageous properties in connection with a commercial audio cassette tape recorder for signal storage. The flexibility of the design extends the scope of application to include not only biomaterial testing but all low frequency data transmissions in biological research.


Pulse width to analog converter for a portable radio telemetry receiver. A pulse width tracking system is described which converts a pulse width modulated telemetry signal into an analog signal. The converter, which is based on an integrated circuit chip design, contains a feedback feature that makes it ideal for high stability servo applications. The converter was designed as an integral part of a long-range radiotelemetry system used in occupational health field research.


[Distribution of afferents from the association nuclei of the thalamus in the projection and association cortex in cats]. Patterns of distribution of terminal degeneration in the parietal cortex (field 7) and in the occipital cortex (field 17) were studied after ultrasonic destruction of the pulvinar by the Fink-Heimer and electron microscopy methods. Degenerating fibers and their terminals were observed in the parietal cortex within all the layers; the greatest amount of degeneration was found in the III--V layers. In the occipital cortex the fibers from the pulvinar end predominantly in the IV layer. Degenerating axons end on the dendritic spines and thin dendritic branches both in the parietal and occipital cortex.


[Vascular component of the systemic circulatory response to orthostasis]. Under the orthostatic test (OT) pronounced compensation of the initial lowering of the arterial pressure (AP) and insignificant restoration of cardiac output arose in anesthetized cats. An important role of the baroreceptor reflexes from the carotid sinus in the mechanism of AP compensation was established. The response of the resistance anc capacitance vessels to OT was studied by the method of extracorporeal circulation. Quantitative evaluation of the blood pooling in the vascular system under OT was made. Compensatory response of the AP under OT was determined mainly by the reflex vasoconstriction of the resistance vessels, but not by the venomotor reactions.


[Damage to the isolated heart due to adrenaline perfused with a saline solution]. Perfusion of the isolated heart with Krebs solution containing 5 and 20 microgram/ml of adrenaline induced cardiocyte micronecrosis. Perfusion with 0.5 microgram/ml of adrenaline induced no micronecrosis. Dispersion analysis showed a statistically significant effect of adrenaline concentrations on the degree of the cardionecrotic effect. The fact of micronecrosis appearance in the isolated heart during its perfusion with saline solution requires revision of the hypothesis on the leading role of blood factor in the realization of the cardionecrotic effect of adrenaline. The appearance of micronecroses with the action of adrenaline in concentrations which activate the mechanism of amines uptake by the heart myocytes speaks in favour of the casual relationship between the accumulation of the biogenic amines by myocytes and the development of their necrosis.


[Autoimmune response following administration of a protein preparation from the caudate nuclei of cattle brains to rabbits]. Plasma membranes of bovine caudate nuclei were solubilized by means of Triton X-100. Detergent-extracted membrane proteins were separated by chromatography on DEAE-cellulose and the affinity adsorbent proposed for the isolation of nicotinic cholinergic receptor protein (N-ChR) from Torpedo electrical organ. Half of the rabbits immunized with purified protein preparation developed a syndrome of myasthenia type. This effect resembled the autoimmune response to N-ChR from fish electrical organs. It is assumed that the N-ChR present in the caudate nucleus has antigen determinants similar to N-ChRs of the electrical organs and skeletal muscles.


[Phenomenon of macrophage spreading in pollinoses]. Macrophages spreading is inhibited by specific allergen in experiments on guinea pigs with a model of pollinosis. Inhibition of macrophages spreading can also be induced by interaction on macrophages of intact guinea pigs with allergens in combination with suitable serum of pollinosis patients. This phenomenon can be utilized in our modification of a test for clinical diagnosis of allergy.


[Antitumor effect of glycopeptides from the cell wall of Lactobacillus bulgaricus]. The antitumor activity of "blastolysin", a preparation that consisted mainly of glycopeptide fragments of the cell wall of Lactobacillus bulgaricus, was studied. Blastolysin was found to exert a specific antitumor effect on sarcoma S-180, leukemia P-388, plasmacytoma MOPC-315, adenocarcinoma AKATOL, melanosarcoma B-16, carcinoma LIC, and spontaneous tumors in mice. It is of low toxicity, does not inhibit hemopoiesis, and its action on tumor tissue differs considerably from that of the known antitumor chemotherapeutic agents.


[Migration capacity of tumor cells treated with immune sera]. The action of antitumour sera on the adhesive properties of the L-cells and the cells of Ehrlich's ascitic carcinoma. It was shown that after the treatment with immune sera the tumour cells lost their capacity to form rosettes with sheep red blood cells, to adhere to plastics and glass; when administered into the mouse organism these cells were worse retained in the lungs, spleen and the liver. The data obtained indicated that the antibodies could play a significant role in the tumour cell metastasis.


[Influence of precursors of endogenously synthesized dimethylnitrosamine on the activity of the demethylase of that carcinogen in rat liver]. Oral administration of dimethylamine, sodium nitrite and a combination of these precursors of endogenously synthesized dimethylnitrosamine to rats increased the activity of demethylase of this carcinogen in the liver microsomes. Under conditions of chronic experiment inclusion of dimethylamine into the diet of rats intensified the demethylase activity even in the presence of casein, an inductor of this enzymatic system. An inhibitor of protein synthesis--actinomycin D prevented an increase of demethylase activity in the microsomal fraction caused by dimethylamine.


[Determination of thyroxine and triiodothyronine in the thyroid glands of encephalectomized rat fetuses]. Concentration of thyroxin and triiodothyronine in the thyroid gland of encephalectomized and intact fetuses of rats with normal and prolonged gestation period was determined by means of isotope methods. Encephalectomy of 19-day old fetuses did not produce any significant effect on the concentration of thyroid hormones in the gland 2 and 4 days after the operation. The results obtained pointed to the absence of the hypothalamic control over the thyroid function in prenatal development of rats.


[Recovery processes in rabbit spleen after hydrocortisone administration]. The effect of hydrocortisone on the rabbit spleen and the recovery processes after the cessation of the hormone injection was studied. A decrease of the absorption function of RES, and spleen atrophy, expressed in a decrease of the organ weight and size followed prolonged hydrocortisons use. Most of the spleen nodes were reduced to an irregular accumulation of lymphocytes. The pyroninophilic cells disappeared in the white pulp. Cessation of the hormone effect was followed by an improvement in the general condition of the animal; the development of the spleen atrophic processes was suspended, the spleen nodes were restored with an increase of pyroninophilic cell count in them. The use of a stimulant under these conditions accelerated the recovery of the animal weight, as well as that of the atrophic spleen, with a normalization of the organ structure.


[Humoral mechanisms of regulating reparative osteogenesis]. The effect of the blood serum of animals with active osteogenesis on the biosynthesis of nucleic acids, protein, and on the mineralization of the regenerating bone tissue was studied in experiments in vivo and in vitro. Incorporation of DNA and protein labeled precursors (3H-thymidine and 14 C-proline, respectively) was increased and the mineralization of the bone callus (85Sr incorporation) was accelerated in the recipients. Comparison of nucleic acids and protein biosynthesis stimulation sequency allows to suppose that the active serum principle promotes the increased cell proliferation in the fracture area.


[Electron microscopic study of the localization of adenylate cyclase in the small intestinal epithelial cells of rabbits with NAG-infections]. As found, in NAG-infection primary intensification of adenylate cyclase activity occurred at the apical plasmalemma of the villar cells; then the process spread to the lateral and further to the basal plasmalemma of the enterocytes. At more advanced stages of NAG-infection an increased adenylate cyclase activity was observed in the crypt cells. Thus, with increased duration of the toxin action there was a gradual rise of the enzyme activity, and the epithelial cells of the small intestine in the area of local affection become involved in the pathological process.


[Effect of alcohol on hepatocyte mitochondria]. The authors studied ultrastructural changes of hepatocytes under the effect of alcohol. The greatest changes were revealed in the mitochondria. Physical activity and hypoprotein diet produced a significant influence on the results of alcohol poisoning. The first factor reduced, and the second enhanced the deleterious effect of alcohol.


[Ultrastructural changes in the parietal cells of persons suffering gastric ulcers]. Ultrastructural changes taking place in various phases of secretion in the gastric fundus parietal cells after histamine adminstration were studied in patients suffering from gastric and duodenal ulcers, having different gastric acidity. Parietal cells of patients with normal and hyperacidity of the gastric juice after histamine administration were found to have such ultrastructural alterations in which were characteristic of the intensively functioning cells, with the retention of phasic character of the process; as to patients with hypoacidity, the secretory phases of the parietal cells were not marked, and no alterations indicating intensification of the cellular functional activity were noted.


[Ultrastructure of erythroid cells in a case of congenital dyserythropoietic anaemia type II (author's transl)]. The ultrastructure of erythroblasts in a case of congenital dyserythropoietic anaemia type II with a negative serum-lysis test is described. The well known symptoms in electronmicroscopy in CDA type I and II are faced to our findings. Morphological changes of hypolemmal cisterns are described and their possible meaning is discussed.


Significance of complement activation in autoimmune haemolytic anaemia of "warm type". To study possible relationships between serum C3 and C4 levels and fixation of complement components (C) on red cells, 79 patients of autoimmune haemolytic anaemia of warm type (AIHA) and 7 patients of various diseases with positive direct antiglobulintest (DAT) but without haemolysis were investigated. 23 out of 79 patients with AIHA were analyzed repeatedly during the course of the disease. There were no significant differences of C levels between the various clinical types. However, the number of patients with reduced levels of C3 and C4 was significantly higher among cases with C fixation on the red cells than among those with fixation of immunoglobulins alone. Changes were more pronounced for C4 than C3 and mean values of serum C4 were significantly lower in the group with C fixation. If incomplete warm haemolysins were demonstrable, C4 levels were lower than in cases without warm haemolysins. During the clinical course, C3 and C4 concentrations showed a close correlation to the severity of haemolysis.


[Severe factor XIII-deficiency. Studies on subunits and turnover of the fibrin stabilizing factor (author's transl)]. An infant with congenital homozygous factor XIII deficiency demonstrated a severe retroperitoneal and intracerebral bleeding with development of a posthemorrhagic hydrocephalus in the first months of life. Factor XIII activity was not measurable by means of enzymatic method and the antiserum inhibition test. Quantitative immunoelectrophoresis according to Laurell presented absence of the subunit A, whereas the concentration of subunit S was reduced to 47% the normal value. After replacement therapy factor XIII activity was estimated at 23% and corresponded to the concentration of the subunit A, concentration of subunit S increased by 20%. The turnover rate of fibrin stabilizing factor could be observed over a period of 39 days. The half life was estimated at 4,7 days. The child developed normally after continous substitution with 250 units of factor XIII concentrate every 6 weeks.


A sensitive latex agglutination method for the detection of soluble fibrin in plasma. A sensitive method is described for the rapid detection of soluble fibrin in human plasma. It is based on the agglutination of Latex particles suspended in a solution of purified fibrin monomers and Blue Dextran 2000. Photometric registration of the decrease in optical density (OD) during agglutination allows the results to be quantitated. The deltaOD depends on the ratio of fibrin monomers to fibrinogen in the tested plasma rather than on the absolute amount of fibrin monomers present.


[Regional pulmonary function in hemidiaphragmatic paralysis (author's transl)]. Gaseous exchange and regional pulmonary function (using 133Xe) were studied in 10 subjects with hemidiaphragmatic paralysis; the paralysis was presumably idiopathic in nine subjects. Global and regional investigations were performed on the same morning, the subjects being studied in the sitting position. Six subjects were obese; nevertheless overweight was moderate except in one case. Lung volumes were moderately decreased (vital capacity ranged from 69 to 100 percent of the predicted value). PaO2 was normal or nearly normal: mean = 75.8 +/- 7.5 torr in the sitting position. PaO2 did not vary significantly in the supine, nor in the lateral recumbent position. AaDO2, breathing air or during hyperoxia, was slightly increased. Qs/Qt was markedly increased in only three cases. Regional lung function data suggest that the paralysed side still plays an appreciable part in pulmonary volume (43.5 +/- 6.3 percent), ventilation (39.1 +/- 8.2 percent) and perfusion (40.4 +/- 9.3 percent). Impairment of the paralysed side was mainly localized in the lower zone; in the middle zone only ventilation was significantly reduced. Results of regional ventilation and perfusion, expressed as absolute values, suggest a redistribution of ventilation and perfusion from the base towards the apex, not only for the paralysed side but also for the opposite side. This adjustment is probably due to the hemidiaphragmatic paralysis but the possible role of obesity (present in six cases) must be kept in mind. Possible therapeutic deductions are discussed.


Effect of growth and aging on the static mechanical lung properties. Quasi-static expiratory pressure-volume curves were obtained in 119 healthy subjects 7 to 64 years old. Lung recoil pressures were measured at six fixed percentages of TLC between 100 percent and 50 percent. In children and adolescents lung recoil pressures increased with growth till about the age of fifteen and there were no differences between sexes. In adults less than 40 years old there was also no sex difference in lung recoil pressures, whereas in subjects more than 40 years old, females had lower recoil pressures than males at every level of TLC. Both in males and females, aging is associated with a marked decrease of lung recoil pressures. Smoking had no detectable effect on lung recoil in males. During growth the evolution of static compliance was closely related to height, whereas in adults this relationship was less evident particularly in males. There was no sex differences in specific compliance which tended to increase slightly with aging.


Acoustic reflex measures of cochlear damage--a normative study. It has been argued that certain reflex measures may indicate the presence of end-organ hearing loss. It has been noticed that the difference between wide band noise and pure tone thresholds is diminished, that the reflex threshold duration function is flattened and that the reflex relaxation index, as specified by Norris et al. (1974b), is reduced in cases of end-organ hearing loss. These aspects of the acoustic stapedial reflex, together with its growth with stimulus intensity, have been investigated in 25 normally hearing subjects. The overriding feature of the measures taken of the acoustic stapedial reflex, was the high inter-subject variability. The differences between the acoustic reflex thresholds for pure tone and WBN was found to be normally distributed about a mean value of 12 dB. The threshold-duration functions again were highly variable and encompassed the entire range of results from normal and end-organ impaired groups as reported by Woodford et al. (1975). The variability encountered in the RRI measures was found to increase with frequency. The growth of the acoustic stapedial reflex with intensity was found to be frequency dependent: the gradient of the function increasing with frequency for the long duration (500 ms) pulses and decreasing with the short duration (50 ms) pulses. It is concluded that considerable caution must be exercised in extrapolation from any one of these measures in isolation.


Improving the reliability of speech audiometry. A necessary feature of good recorded speech material is that each list should be identical in respect of graded order of difficulty. Extensive validatory tests have been carried out upon 20 M.R.C. word lists re-recorded by a professional announcer. It can be shown that by various manipulative procedures appreciable improvements may be obtained in the confidence limits of the material. In addition studies have been carried out upon the relationship between Speech Detection Threshold (S.D.T.) Speech Reception Threshold (S.R.T.) and Hearing level (H.L.) in normal hearing subjects. The surprising finding is that both S.D.T. and S.R.T. appear to be relatively independent of H.L. An analysis has been made of the words comprising the material in respect of their ease of recognition and is presented as an appendix.


Within- and between- subject variability of indices from the closing volume and flow volume traces. The within-subject variability of consecutive measurements of indices derived from the closing volume (CV) trace and from the maximal expiratory flow volume (MEFV) curve was studied in 24 subjects. The variability of the closing volume and of the maximal expiratory flow rates at 50 percent (Vmax. 50) and 75 percent (Vmax. 75) of the expired vital capacity was about three to eight times greater than that of the FEV1, FVC or FEV1 percent. The lung volume measured from total lung capacity to the onset of airway closure (OAC) was about five times more reproducible than the CV. The coefficients of variation for the CV (as a percentage of the vital capacity), the Vmax. 75, and the OAC, both in litres and as a percentage of the vital capacity, were significantly correlated with age. No difference in the mean coefficients of variation for the CV, OAC, Vmax. 50 or Vmax. 75 were found with respect to sex, smoking habit or previous experience with the test routines. The between-subject variability of the FEV1, FVC, FEV1 percent, transfer factor, diffusion coefficient, Vmax. 50, Vmax. 75, CV and OAC was evaluated from a study of 75 asymptomatic lifetime non-smokers. The variability of the Vmax. 50, Vmax. 75 and CV was about two to eight times greater than that of the other tests used, irrespective of sex. The OAC (percent VC) was three to four times less variable than the CV. The variability of the Vmax. 50 and Vmax. 75 was reduced by, on average, 7 percent when these flow rates were expressed per litre of FVC.


[Effect of bronchodilators on density dependence of expiratory flow-volume curves. An attempt to localize bronchodilators site of activity (author transl)]. In order to localize bronchodilators site of activity we studied the maximal expiratory flow-volume curves breathing air and 80 percent-20 percent helium-oxygen mixture in 11 normal and 23 asthmatic children. We measured delta Vmax. 60 percent TLC. delta Vmax. 45 percent TLC and VisoV. Half of the subjects received 400 gamma of fenoterol (beta2-sympathicomimetic), the other ones 200 gamma of SCH 1000 (synthetic atropine). Whatever the bronchodilator used, we found different types of response: 1 degree No modification in comparison with control period; 2 degree Increase of deltaVmax. with decrease of VisoV; 3 degree decrease of delta Vmax. with rise of VisoV. Thus we were unable to show a specific bronchodilator site of activity. However, in a few subjects, SCH 1000 principally acted on large airways whereas in some others fenoterol essentially acted on small airways.


[Critical study of a new method for measuring total CO2 in plasma (author transl)]. A new analyser for total CO2 in blood--Ericsen E-100--has been tested and its performances compared with those of the manometric Van Slyke apparatus. Ericsen E-100 makes it possible to measure very small samples (50 microliter) in a short time (35 s). It appears that Ericsen E-100 underestimates total CO2; the higher the total CO2 the larger the error. Simple improvements are suggested, especially concerning the way injection is performed in the reaction chamber.


[Reversibility of airway obstruction in asthma and chronic bronchitis (author transl)]. Our purpose was to determine whether, in patients with airway obstruction, the change in the forced expiratory volume in one second (FEV1) which occurs after a bronchodilator drug, is helpful in differentiating asthma from chronic bronchitis. Two groups of patients (48 with asthma and 42 with chronic bronchitis) having a comparable level of initial airway obstruction were selected according to clinical criteria. After salbutamol (200 microgram inhaled) the number of subjects showing a change in FEV1 of at least 20 percent of its initial value or 10 percent of its predicted value was significantly greater (p less than 0.01) in the asthmatic than in the bronchitic group. Lesser changes in FEV1 did not significantly separate the two groups. When the changes in FEV1 were expressed as percentages of both initial and predicted values, the number of positive responses increased in the asthmatic group. However, there were still 20 asthmatics with little or no change in FEV1 after salbutamol who could not be distinguished from the patients with chronic bronchitis. From these data we conclude that, in patients with airway obstruction, a large bronchodilator-induced change in FEV1 strongly suggests the diagnosis of asthma but that the presence of "irreversible" airway obstruction does not disprove it.


The effects of bradykinin and the bradykinin potentiating peptide BPP5a on the electrical and mechanical responses of the guinea-pig taenia coli. 1 By means of the double sucrose-gap technique, the effects of bradykinin and the bradykinin potentiating peptide BPP(5a) were compared on the guinea-pig taenia coli under a number of experimental conditions.2 In normal Krebs solution the response to bradykinin was mostly a slight stimulation, characterized by a depolarization, an increase in spontaneous spike activity and a contraction. If BPP(5a) caused any effect at all, it was stimulation of the spike activity but without depolarization. Since the effect of bradykinin was little affected by an increase in dose, a potentiating effect of BPP(5a) could not be determined.3 Spontaneous spikes with a 5 to 7 s rhythm and prepotentials at their base were inhibited by bradykinin, whereas they were stimulated by BPP(5a).4 Oscillatory potentials (slow waves) induced by a calcium and magnesium-free medium were also suppressed by bradykinin and stimulated by BPP(5a). This effect of bradykinin was accompanied by a depolarization and a decrease in membrane resistance, phenomena not found after administration of BPP(5a).5 The amplitude of spontaneous spikes induced by potassium-depolarization was suppressed by bradykinin, even though the membrane resistance and potential had been decreased. BPP(5a) produced either no effect or a small stimulatory effect without influencing the membrane resistance.6 Reduction of the calcium concentration to 0.25 mM enhanced the stimulatory responses to both bradykinin and BPP(5a), especially the spike activity and depolarization. In this case the membrane resistance was increased by bradykinin as well as BPP(5a). These effects, especially those of BPP(5a), were inhibited by reduction of the sodium concentration to 15.5 mM. Reduction of the chloride concentration to 9.7 mM decreased rather than increased the stimulatory effects of both bradykinin and BPP(5a). Under these conditions bradykinin did not decrease the membrane resistance.7 Bradykinin can have both inhibitory and stimulatory effects on the taenia coli whereas BPP(5a) has only a stimulatory effect. Since under certain conditions both responses to bradykinin are accompanied by a sodium-dependent depolarization and decrease in membrane resistance, not influenced by lanthanum to any extent, it is suggested that bradykinin induces an increase in sodium conductance of the membrane. Under all the conditions investigated, except in low calcium, BPP(5a) did not affect the membrane potential and resistance. Thus, the underlying cause of its stimulatory effect is probably different from that of bradykinin.


The contribution of prostaglandins in the muscle of human isolated small intestine to neurogenic responses. 1. In stris cut parallel to the longitudinal or circular muscle, indomethacin (2--10 microgram/ml) usually lowered the tone, thus probably accounting for the reduction of nerve-mediated relaxations to electrical field stimulation. 2. In longitudinal muscle strips, indomethacin enhanced contractions which occurred during electrical stimulation, probably because tone fell, but antagonized after-contractions. By contrast, in the circular muscle indomethacin reduced initial contractions but enhanced after-contractions. 3. Prostaglandin E2 counteracted all of the effects of indomethacin in the longitudinal muscle and most of those in the circular muscle; prostaglandin F2alpha restored circular muscle tone. 4. The results suggest that prostaglandins affect the muscle directly and contribute to the regulation of tone. They may also mediate non-cholinergic contraction in longitudinal muscle and suppress contractility in the circular muscle.


Estimation and characterization of prostaglandins in the human gastrointestinal tract. 1 Prostaglandin-like material was extracted from muscle and mucosa of surgically removed human stomach, ileum and colon and assayed against prostaglandin E(2) on strips of rat gastric fundus. Superfused human isolated gastric mucosa released prostaglandin-like material and release was increased by stretching or clamping the tissue.2 The relative amounts of extracted biological activity were broadly as follows: gastric antral mucosa > colon muscle > gastric body mucosa approximately ileal mucosa > colon mucosa approximately gastric muscle approximately ileal muscle.3 Prostaglandin E and F were tentatively identified by chromatography and sensitivity to inactivation by alkali.4 Prostaglandin E apparently contributed most to the biological activity, possibly because the assay tissue is more sensitive to prostaglandin E than to F. Chromatography of gastric body mucosal extracts located material running with prostaglandin E(2) and a little with E(1). Colonic muscle and mucosal extracts contained material with R(F) values of prostaglandins E(1), E(2), E(3) and F(1a), whereas F(2a) and F(3a)-like substances were found only in the mucosa. The proportions of prostaglandin F varied between specimens.5 The amount of extracted prostaglandin-like activity was increased by adding cofactors and arachidonic acid, and lessened by homogenization with acid-ethanol.6 The type and amount of activity generated from arachidonic acid by partly purified colonic mucosal prostaglandin synthetase depended on the substrate concentration.7 The possible relationships of prostaglandins to mucus secretion and other physiological and pathological gut functions are discussed.


The influence of vasoactive substances on blood flow and contractile responses of cat gastrocnemius. 1 The effects of several vasoactive substances have been studied on blood flow and acetylochline-induced contraction of the vascularly isolated gastrocnemius of the cat. All substances, including acetylcholine, were administered intra-arterially to the muscle. Blood flow and contractile tension were monitored simultaneously.2 All substances which increased blood flow, enhanced the contractile responses to acetylcholine; angiotensin, which decreased blood flow, attenuated them.3 Histamine was typical of the vasodilators in doses up to 1 mug (9 nmol), but in a dose tenfold higher it produced only a small and transient increase in blood flow and little or no enhancement of the acetylcholine-induced contractions. These paradoxical effects were brought about by that portion of the high dose of histamine which re-entered the cat's systemic circulation.4 The order of potency of the vasodilators was the same for their potentiating effect on the acetylcholine-induced contractile responses as for their enhancing effect on muscle blood flow: bradykinin >histamine>>papaverine>>NaH(2)PO(4) >KCl. Median effective doses (ED(50)S) determined only for bradykinin, histamine and papaverine were, respectively, 20.5, 49.8, and 3,352 pmol as potentiators, and 13.4, 199.8 and 85,000 pmol as vasodilators.5 In general, the effect of a given vasoactive substance on the contractile response to acetylcholine was dose-dependent and correlated well with its effect on muscle blood flow at the moment the acetylcholine was injected. Two important exceptions were, firstly, that the highest dose of papaverine was only moderately effective as a potentiator even though highly effective as an increaser of muscle blood flow; and, secondly, that histamine produced its greatest potentiating effect 10 s after it was injected, at which time its effect on muscle blood flow was quite small.6 It is suggested that these exceptions and, indeed, the much greater potentiating effectiveness of histamine and bradykinin versus papaverine may be due to the ability of histamine and bradykinin to increase the permeability of the muscle's capillaries as well as increasing blood flow through them, thus facilitating much better than mere vasodilators the access of bloodborne acetylcholine to its receptors on the muscle fibres.


Pathways of prostaglandin F2alpha metabolism in mammalian kidneys. 1 High-speed cytoplasmic supernatants of rat, rabbit, pig and guinea-pig kidneys were prepared and the metabolism of 10 mug/ml prostaglandin F(2alpha) labelled with [(3)H(1)-9beta]-prostaglandin F(2alpha) studied by thin layer radiochromatography and bioassay.2 The metabolism of prostaglandin F(2alpha) measured by radiochromatography parallels biological inactivation in all species except the rabbit.3 Kidneys metabolize prostaglandin F(2alpha) by two divergent pathways, yielding a mixture of prostaglandin E and F metabolites.4 15-Hydroxyprostaglandin dehydrogenase and prostaglandin Delta-13 reductase are present in all species in characteristic proportions. Thus prostaglandin F(2alpha) is metabolized sequentially to 15-keto prostaglandin F(2alpha) and 13,14-dihydro-15-keto prostaglandin F(2alpha). The rate and profile of formation of these metabolites is species-dependent.5 13,14-Dihydro-15-keto prostaglandin F(2alpha) is the principal prostaglandin F series metabolite in all species.6 Pig and guinea-pig kidney contain an unidentified enzyme which converts 13,14-dihydro-15-keto prostaglandin F(2alpha) to 13,14-dihydro prostaglandin F(2alpha).7 Rat kidney contains a high concentration of a prostaglandin 9-hydroxy dehydrogenase which converts 13,14-dihydro-15-keto prostaglandin F(2alpha) to 13,14-dihydro-15-keto prostaglandin E(2).8 Rabbit kidney contains a novel 9-hydroxydehydrogenase which oxidises prostaglandin F(2alpha) directly to E(2), thus producing a compound with more potent renal actions. The possible implications of this enzyme for kidney homeostasis are discussed.


The distribution of methionine-enkephalin and leucine-enkephalin in the brain and peripheral tissues. 1 A method is described for the rapid extraction of opioid peptides from the brain and other tissues. The method is based on acid extraction of tissues followed by adsorption of the extract onto Amberlite XAD-2 resin. Elution with methanol separates the enkephalins and alpha-endorphin from beta-endorphin.2 Over 90% of the opioid peptide activity isolated from brain and gut of several species by our method was due to methionine- and leucine-enkephalin. In contrast, the major opioid peptide activity recovered from the pituitary was due to peptides of much greater mol. wt. than the enkephalins.3 An opioid peptide with properties unlike those of the known endorphins or enkephalins was present in brain extracts. This peptide, termed epsilon-endorphin, has an apparent mol. wt. of 700 to 1200; it constituted between 5 to 10% of the total opioid activity in our extracts.4 A differential assay of methionine- and leucine-enkephalin was made either by destroying methionine-enkephalin activity with cyanogen bromide or by separating the peptides by thin layer chromatography.5 The ratio of methionine-enkephalin to leucine-enkephalin varied greatly in different brain regions. The highest proportions of leucine-enkephalin were found in the cerebral cortex and hippocampus.6 Formaldehyde perfusion and fixation of the brain in vivo had no significant effect on the brain content of enkephalin, indicating that proteolytic breakdown is not a major problem in the extraction of these peptides.7 It is suggested that the enkephalins may have a neurotransmitter role in both brain and peripheral tissues and that methionine- and leucine-enkephalin may subserve separate neuronal functions.


Comparative potencies of amphetamine, fenfluramine and related compounds in taste aversion experiments in rats. 1 Rats failed to drink a flavoured solution when its consumption had been followed by injection of amphetamine (conditioned taste aversion).2 There was very little difference between the potencies of (+)- and (-)-amphetamine.3p-Chloromethamphetamine was a more potent aversive agent than methamphetamine.4 Strong taste aversions were also conditioned with other congeners of amphetamine. The rank order of potency was: fenfluramine > chlorphentermine >p-hydroxyamphetamine.5 Cocaine induced only moderate taste aversions, even at high doses.6 Aversive potency did not appear to be correlated with known neurochemical actions of the drugs or with behavioural stimulation, but appeared to be a central action which may have been linked to anorexigenic potency or time course of action.


Respiratory and circulatory effects of saxitoxin in the cerebrospinal fluid. 1 In cats anaesthetized with pentobarbitone, saxitoxin and, on a few occasions, tetrodotoxin were injected into a lateral cerebral ventricle or into the subarachnoid space of the lower brain stem. Observations were made on frequency and tidal volume of breathing, on CO(2) responsiveness and on electrical responsiveness of the respiratory centre. Effects on the blood pressure were observed simultaneously.2 A single large dose of toxin, e.g., 250 ng, produced within minutes apneustic breathing and a rise in blood pressure which were converted rapidly to respiratory failure and hypotension. In contrast, repeated small doses, e.g., 25 ng, yielded only progressive slowing of the respiration together with circulatory hypotension. Bulbar depression was produced as effectively by subarachnoid injection as by intraventricular injection of the toxins. Onset of action was detectable within seconds.3 Slowing of the respiration occurred independently of change in tidal volume and whether or not the vagus nerves were cut. The reduction in breathing frequency is attributed to direct toxin-induced depression of the central respiratory oscillator.4 Steady-state measurements of tidal volume at controlled levels of alveolar CO(2) pressure in intermediate stages of respiratory depression showed that the toxins produced an increase in CO(2) stimulation threshold as well as a reduction in gain of CO(2) responsiveness, whether or not the vagus nerves were cut. Carotid arterial chemoreceptor reactivity to O(2) was demonstrable when central sensitivity to CO(2) was depressed. These effects are attributed to a direct influence of the toxins upon the brainstem CO(2)-tidal volume controller.5 Responsiveness of the medullary inspiratory centre to electrical stimulation persisted after the failure of spontaneous breathing was caused by the toxins. Conversely, restitution of electrical responsiveness preceded the reappearance of spontaneous respiratory activity in the recovery phase of toxic depression. Circulatory effects paralleled the changes in respiratory behaviour.6 On the basis of the relatively prompt and discrete alterations in the central respiratory and circulatory control mechanisms produced by saxitoxin and tetrodotoxin placed in the cerebrospinal fluid, it is concluded that the agents rapidly penetrated to deep target loci in the lower brain stem.


Actions of 16-aryloxy analogues of prostaglandin F2alpha on preparations responsive to prostaglandin endoperoxides. On four prostaglandin endoperoxide-sensitive preparations, namely human platelets in vitro, rabbit aortic strip, guinea-pig tracheal chain and pig blood pressure, ICI 79939 and its 11-oxo analogue mimicked the actions of 11,9-(epoxymethano) prostaglandin H2, and were considerably more active than either prostaglandin F2alpha or ICI 81008. It is suggested that this activity of ICI 79939 may contribute to its toxicity in experimental animals.


Perceived illness and its treatment. A naturalistic study in social medicine. This is the initial report of a longitudinal study conducted in a developing, culturally heterogeneous society. The study compares figures of frequency and length of perceived illness, subjective reports of biological and behavioural symptoms, and use of medical facilities in response to episodes of illness by female heads of households from two highly distinctive social-ethnic groups. Despite differences in socioeconomic status and cultural beliefs about disease and treatment, both groups showed roughly comparable rates of perceived illness, but certain differences were noted. The more prosperous Western group termed ladinos, showed they had had more illness which had also lasted longer, as well as higher levels of symptoms. The medical actions of the two groups in response to these episodes of illness differed. The significance of these results is discussed with respect to the multiplicity of factors which influence health status and judgements of perceived illness.


Why do women consult doctors? Social factors and the use of the general practitioner. This study was designed to investigate personal and social factors associated with demand for care by women aged between 20 and 44 years, a group unlikely to suffer from chronic illness. A random sample of women was drawn from the age-sex register of a south London group practice, and information was obtained concerning their daily symptom perception, anxiety level, social and health characteristics, and their consultations for one year. Social class, family involvement, number of children in household, satisfaction with the housing, and use of other health and social services were not associated with demand for general practitioner care. Absence of basic housing amenities, difficulties in running the household, brevity of stay in the house or neighbourhood, and lack of attachment of the neighbourhood were related to a high patient-initiated consultation rate. Some of the possible interpretations of these results are discussed together with their implications for social policy planning.


A study of the organisation and functioning of the obstetric services in a health district. A study was undertaken into the obstetric services of a health district to find out whether the new purpose-built obstetric accommodation was still needed and, if so, the best method for bringing it into use. If it was not required for its original purpose it was hoped that the study would reveal an alternative use. It was also hoped that the study would answer any further questions that might emerge from the investigation. The study showed that the purpose-built obstetric accommodation was not a present required. It was recommended that the 22 obstetric beds should be used for gynaecology and that the accommondation upgraded earlier for that purpose should form part of the geriatric provision.


Social group and mortality in Finland.

Social group and mortality in Finland. Morality rates for various social groups within the population of Finland were compared, using 179 919 death certificates for the period 1969-72. Morality was generally lowest in the highest social groups and highest among unskilled workers. Male mortality from coronary heart disease was also high among lower salaried employees. In the less developed area of northern Finland, female mortality from coronary heart disease and vascular lesions of the central nervous system was highest among the agricultural population. Cancer of the breast, cancer of the intestine, and suicides among women were apparently concentrated in the higher classes. Life table analysis showed that the social group differences in life expectancy at birth could be as great as 7.2 years. It is considered indispensable for a national health policy to improve on the recording of occupational data and to give regularly the occupation of the deceased when publishing mortality rates.


Selective screening for cervical cancer. Experience of the Finnish mass screening system. Names of women eligible to be screened for cervical cancer are taken from the national population registry and the women are invited by a personal letter. The data, from these mass screenings are analysed and stored at the screening registry. To reduced the costs of the system and to increase the yield of preinvasive lesions the idea of selective screening was considered. Tt was decided that if people were selected according to their risk factors, as recorded in the national population registry, the screening would be ineffective as many cases of invasive cancer were found in the low risk groups. High risk factors were determined from anamnestic data on systems and from previous cytological diagnoses. The proportion of women with symptoms of bleeding or the class II-V smears without positive histological results constituted fewer than 10% of the participants, but 20% and 40% respectively of invasive carcinomas were found in these groups during the subsequent follow-up period. Thus it is suggested that selective screening apart from that based on age has a limited application and should be restricted mainly to the interval between the organised screenings, which in Finland is five years.


Geographical variation mortality from ischaemic heart disease in England and Wales. Analysis ofthe proportional mortality attributed to ischaemic heart disease, adjusted for age, reminds us that many of the well known geographical, environmental, social, and economic variations within England and Wales are not disease specific.