Leucocyte alkaline phosphatase as a marker of cell maturity: a quantitative cytochemical and autoradiographic study. A sensitive and reproducible cytochemical technique for the demonstration of leucocyte alkaline phosphatase (LAP) has been evaluated. It produces a stable reaction product which can be readily quantified microphotometrically. In the circulating neutrophil polymorphonuclear leucocytes of rats the mean LAP levels measured in this way fluctuated only slightly from day to day. A highly significant correlation was demonstrated between LAP levels of neutrophils and their age, determined by isotope labelling with tritiated thymidine and by nuclear morphology. The correlation between the age of neutrophils and the complexity of their nuclear morphology has also been confirmed. The technique provides a useful tool for the study of leucocyte kinetics in disease states.


Ultrastructural studies of the bone marrow in sickle cell anaemia. II. The morphology of erythropoietic cells and their response to deoxygenation in vitro. Electron microscopic studies of bone marrow aspirates obtained from patients with homozygous sickle cell anaemia (HbSS) were fixed immediately without attempts to deoxygenate the samples. Erythroblasts and normoblasts in these preparations were devoid of haemoglobin polymers or other indications of sickling. Furthermore, the nucleated erythroid cells from sickle-cell patients presented an ultrastructural morphology indistinguishable from that of identically-processed erythroid cells in marrow samples from normal human volunteers. This report presents a description of the ultrastructural features of pronormoblasts and normoblasts in normal and sickle-cell marrows and stresses the essentially normal appearance of nucleated erythroid elements in sickle cell anaemia. Exposure of sickle-cell marrow aspirates to nitrogen at 37 degrees C for 30 min resulted in haemoglobin polymerization in most erythrocytes and reticulocytes but only in 10-20% of the nucleated erythroid cells. Haemoglobin polymers in the form of intertwining fibre meshworks were observed in reticulocytes, orthochromatic and polychromatophilic normoblasts, but were absent in basophilic normoblasts and pronormoblasts. The results suggest that the concentration of haemoglobin in intramedullary normoblasts may be the limiting factor determining the predisposition of these cells to undergo sickling as well as the pattern of haemoglobin aggregation. Under the physiological conditions prevailing in the marrow, haemoglobin concentration in normoblasts may be insufficient to result in aggregation and polymerization.


Splenectomy in homozygous beta thalassaemia: a retrospective study of 30 patients. In order to clarify the indications for splenectomy in patients with homozygous beta thalassaemia we studied, retrospectively, the basal pre-transfusion haemoglobin levels and blood transfusion requirements before and after splenectomy, in a series of patients with this disorder. Thirty-six patients, of whom 20 underwent splenectomy, were included in this study. Three groups of patients with homozygous beta thalassaemia were identified on the basis of clinical and laboratory findings. Two of the three groups consisted of 24 patients with beta thalassaemia major, subdivided retrospectively according to their response to splenectomy. The third group consisted of six patients with beta thalassaemia intermedia who had a comparably mild clinical course. In the first group of 16 patients with beta thalassemia major, monthly transfusions were required from the age of 6 months to 24 months and splenectomy resulted in temporary improvement for a period of 1-2 years. Thereafter, the transfusion requirements returned to pre-operative levels with no sustained improvements in base-line pretransfusion haemoglobin levels. Despite the fact that haematological improvement was temporary, it is felt that splenectomy is indicated in this group since the development and the general well-being of the children was significantly improved. In the second group of eight patients with beta thalassaemia major, transfusion requirements were relatively infrequent before 1-2 years, but after several years the transfusion requirement increased simultaneously with the development of 'hypersplenism'.


Regeneration of intact spleen in a heterotropic site in splenectomized mice. The regeneration of intact spleens implanted in the sacrospinal areas of splenectomized mice was studied by light microscopy. The weight of the implanted tissue was not fully regenerated 50 days after implantation. The pattern of embryonic development of the spleen was investigated and the histologic appearance of the implant 46 days after implantation resembled that of normal spleen. The appearance of primitive myelopoietic stem in cells in the early phases of regeneration makes this an attractive model in which to study the biologic effects of tumour viruses.


Classification of radiological appearance and the derivation of a numerical score. Approaches to the use of the International Labour Office U/C Classification of radiological appearances are considered in the context of multiple readers recording different degrees of abnormality. The Panel on Survey Radiology has been set up to provide a basis for standardization. An example of how the panel may be used in this role is given. The approach will depend on the standards maintained by the panel and on a greater understanding of the appearances associated with differing exposures.


Comparative study of the smooth muscle contractor activity of airborne dusts and of dustiness in cotton, flax, and jute mills. A bioassay technique using isolated guinea-pig ileum was employed to compare the smooth muscle contractor activity of various dusts from mills in which the prevalence of byssinosis was known. The activity of dust from a mill spinning a coarse grade of cotton was several times greater than that in dust from a mill processing a fine grade of cotton. There was a similar order in the difference of the prevalence of byssinosis in these mills. However, the activities of fine cotton, flax, and jute dusts were very similar to each other, in spite of marked differences in the prevalence of byssinosis in these mills. For cotton dust, smooth muscle contractor activity was associated with all particle sizes, although the lowest level of activity was found in the largest sized fraction (less than 2 mm). Activity in the cotton dust extracts was not correlated with nitrogen, carbohydrate, or potassium content. However, about one-fifth of the activity of a cotton dust extract was associated with an insoluble particulate fraction. The possible chemical nature of the water-soluble contractor agent is discussed. It is concluded that, until the role of this agent in the pathogenesis of byssinosis has been established, the bioassay technique cannot be employed as a means of assessing the byssinogenic potential of cotton dust.


Epidemiological investigation of the role of family susceptibility and occupational and family histories in the development of byssinosis among workers exposed to flax dust. Epidemiological investigation of 475 workers exposed to dust in flax processing has shown that family susceptibility has a decisive role in the development of byssinosis in those workers. Workers whose fathers had occupational history of exposure to flax dust were more resistant to the development of the disease than those whose fathers had no such history. Such tolerance was much higher in workers whose fathers were byssinotic than those with byssinosis-free fathers. Further hereditary and immunological investigations are, however, needed.


Occupational asthma after inhalation of dust of the proteolytic enzyme, papain. Papain is a proteolytic enzyme widely used by biochemists. In experiments on animals papain has been shown to cause emphysema either when they inhaled a single small dose or after intratracheal inhalation. Four food technologists were occupationally exposed to heavy concentrations of papain dust in air. Subjects 1 and 2 developed an immediate acute asthmatic reaction, and symptoms of obstructive airways disease persisted for some months while each remained in the same working area, presumably exposed to small gradually diminishing amounts of residual papain dust. Tests of respiratory function were carried out on all four subjects 1 1/2 years later and showed in subjects 1 and 3 minimal abnormality of bronchial reactivity and of ventilation distribution. Review of the literature reveals only two reports of asthma resulting from papain inhalation, although its antigenic and skin sensitizing qualities have been known and described for many years. It seems remarkable that a substance such as papain, shown to be a potent cause of lung damage in experimental animals, should have produced so little evidence of abnormality in our subjects after considerable exposure. Follow-up ventilatory function tests may cast further light on this but we postulate that the asthmatic response may be biologically protective and those lacking this reaction could later develop emphysema as a long-term outcome.


Effect of hydrofluoric acid on glucose metabolism of the mouse studied by whole-body autoradiography. Distribution of radioactive carbon from [U-14C]glucose in the mouse poisoned by hydrofluoric acid has been studied by whole-body autoradiography. Under normal conditions, the highest autoradiographic density was found in the Harder's gland, palatine gland, sublingual gland, large intestinal mucosa, and many regions of the central nervous system 30 minutes after intraperitoneal injection of [U-14C]glucose. On the other hand, after hydrofluoric acid poisoning, it was found that (1) the radioactivity of brain was unchanged throughout all the poisoning; (2) the liver, renal cortex, lung, and blood showed an increase in radioactivity at 180 minutes of poisoning; (3) the abdominal cavity showed a tendency to residual radioactivity with the poisoning; (4) by contrast, Harder's gland, the palatine gland, sublingual gland, and large intestinal mucosa showed a decrease in radioactivity at 180 minutes of poisoning.


The effects of dietary calcium and phosphorus on the retention and excretion of lead in rats. 1. Rats were given diets containing different amounts of calcium, phosphorus and lead. 2. Pb retention was greatly increased when the diets contained less Ca or P than the minimum estimated requirement of the rat. 3. The release of Pb already incorporated into the skeleton was inhibited by diets low in Ca but was not affected by diets low in P. 4. The retention of Pb given intraperitoneally was not affected by dietary Ca or P. 5. It can be concluded that dietary Ca and P influence the absorption of Pb by the gut and dietary Ca influences the metabolism of Pb in the bone. 6. There were changes in the distribution of Pb among the tissues due to changes of dietary Ca. 7. At low body concentrations, Pb probably affected skeletal growth.


The effect of feeding high levels of low-quality proteins to growing chickens. 1. Three growth trials were done using male broiler chicks. In the first two trials, groundnut meal was used, with and without supplementary methionine and lysine. In the third trial, soya-bean meal was used with and without supplementary methionine. Protein levels ranged in the first trial from 120 to 420 g/kg diet and in the third trial from 120 to 300 g/kg diet. Thus the assumed minimal amino acid requirements of the chick were supplied by high levels of low-quality dietary protein. 2. Diets based on cereals and groundnut meal did not support maximum live-weight gain or maximum efficiency of food utilization at any level of dietary protein. When the principal deficiencies of lysine and methionine were corrected, this protein mixture was capable of supporting the same growth rate as a control diet of cereals and herring meal. 3. Diets based on maize and soya-bean meal did not support quite the same growth rate as similar diets supplemented with methionine, even though the protein level in the unsupplemented diets was sufficient to meet the assumed methionine requirements. 4. These results are interpreted as examples of amino acid imbalance in diets composed of familiar feeding-stuffs. It is concluded that one cannot assume that the poor quality of a protein source can always be offset by increasing the concentration of dietary protein.


The effect of glucose infusion on the plasma free amino acids in sheep. 1. Glucose in solution in saline, or saline alone, was administered to a group of twenty ewes during late pregnancy and again after lambing. Sequential blood samples were taken before and after the infusion and the concentration of plasma free amino acids was determined. 2. The effect of glucose was to reduce the concentrations of all amino acids except alanine. The reduction was greatest for tryptophan in the pregnant sheep, but this amino acid showed no significant change in the lactating animals. 3. An attempt to rank the amino acids on the basis of their response to glucose infusion indicated  that, with the exception of tryptophan for the preparturient ewes, groups of essential amino acids could not be distinguished from each other. These groups were, for the preparturient sheep, valine, leucine, phenylalanine and isoleucine, and for the postparturient animals, isoleucine, lysine, methionine, valine and phenylalanine.


Studies on the nutrition of marine flatfish. The thiamin requirement of turbot (Scophthalmus maximus). 1. Seven groups of young turbot (Scophthalmus maximus) were given diets containing graded levels of thiamin (0-19--50 mg/kg) for 16 weeks and their growth rate was measured during this period. 2. Good growth was obtained on all these treatments except in the group given the lowest dietary thiamin level (0-19 mg/kg). These fish grew normally until the 12th week but thereafter their weight did not increase. 3. Measurements of erythrocyte transketolase (sedoheptulose-7-phosphate: D-glyceraldehyde-3-phosphate glycolaldehydetransferase; EC 2.2.1.1) activity at the end of the experiment and of percentage stimulation of erythrocyte transketolase by thiamin pyrophosphate indicated that the apoenzyme was saturated with coenzyme at a dietary thiamin level of 2-6 mg/kg, but not at 1-1 mg/kg. 4. An 8th group of turbot given the thiamin antagonist pyrithiamin (40 mg/kg diet) grew normally for 6 weeks. Thereafter mortalities began to occur and all fish died by the 10th week. No clear-cut signs of thiamin deficiency were observed. 5. The dietary thiamin requirement of turbot is much lower than published requirements of freshwater fish other than carp (Cyprinus carpio) and appears to be between 0-6 and 2-6 mg/kg diet.


Variations in the apparent nutrient content of foods: a study of sampling error. 1. Successive portions of boiled and mashed potatoes, roast pork, cooked, freeze-dried peas and ice-cream were taken in order to determine the total (sampling and experimental) error involved in the 'duplicate analysis' method of dietary survey. 2. These samples were analysed for water, nitrogen, fat, iron and energy. 3. The experimental error of the methods was also studied separately. 4. The sampling and experimental errors ranged from 0-3% for water in potatoes, to 23% for Fe in ice-cream. Sampling error was significantly greater than experimental error for all nutrients studied. 5. It is concluded that in reporting the results from dietary surveys, it is necessary to take account of the erros inherent even in the most precise methods.


Vitamin B12 metabolism in the fruit bat (Rousettus aegyptiacus). The induction of vitamin B12 deficiency and its effect on folate levels. 1. Vitamin B12 metabolism was studied in bats of the species Rousettus aegyptiacus, which live on an all-fruit diet in the wild. 2. There was a wide range in values for the serum vitamin B12 concentration of newly captured bats, but bats captured in the early spring had significantly higher mean serum vitamin B12 levels than bats captured in the early autumn. 3. There was an exponential decrease in serum vitamin B12 concentration with time in captivity for bats fed on a vitamin B12-deficient, all-fruit diet; the biological half-life was 80 d in serum, 109 d in liver and 164 d in kidney. 4. The main storage organ for vitamin B12 in the bats was the liver, mean content 1067 ng vitamin B12. After 50 d, injected [57Co]cyanocobalamin had equilibrated with body vitamin B12 stores, and 17% of the retained radioactivity was present in the liver. From these results it was calculated that the total body vitamin B12 content of the bat was c. 6500 ng. 5. The biological half-life of injected [57Co]cyanocobalamin was 70--88 d and the calculated daily requirement was 50--60 ng (0-2 mug/kg body-weight per d). 6. As serum vitamin B12 levels decreased, serum folate levels increased. The erythrocyte folate concentration increased significantly after 130 d on the all-fruit diet and then decreased to the initial values after 190 d. 7. Vitamin B12 metabolism in the fruit bat is similar in many respects to that of man, but on a 'weight-for-weight' basis the bat has a 5- to 15-fold greater requirement for this vitamin. 8. Vitamin B12 deficiency may be induced fairly rapidly in fruit bats fed on an all-fruit diet.


The role of organic sulphur in the copper-molybdenum-S interrelationship in ruminant nutrition. 1. The ability of organic and inorganic sulphur to influence the copper and molybdenum metabolism of sheep was compared in a series of three 2 X 2 factorial design experiments. In each experiment, four groups of five to seven hypocupraemic ewes were repleted with a basal diet supplemented with 6 mg Cu/kg and containing S and Mo at one of two concentrations, 1 or 4 g S and 0-5 or 4-5 mg Mo/kg respectively. Sodium sulphate (Expt I), methionine (Expt 2) or cysteine (Expt 3) were used as the S sources. Cu and Mo concentrations in plasma were estimated in each experiment and in Expt 3 the concentrations of Cu in liver and Mo in urine were also estimated. 2. The effects of the three S sources on Cu and Mo metabolism were similar. Repletion of the plasma Cu pool was unaffected by Mo alone, reduced by S alone and totally inhibited by Mo+S. Plasma Mo was greatly increased by Mo supplements, slightly decreased by S supplements and unaffected by Mo and S supplements given together. 3. In Expt 3 the treatments were found to affect urinary Mo and plasma Mo in a similar manner; S prevented dietary Mo from increasing Mo excretion. The only group to show a significant repletion of the liver Cu pool was that given Mo alone. 4. Supplementation of the diet with organic S significantly reduced the within-treatment variation in plasma Cu and Mo. liver Cu and urinary Mo. 5. It is suggested that variations in dietary S and Mo within the normal range for herbage affect the Cu and Mo metabolism of the grazing animal, and that total S rather than inorganic S is the more useful measurement in the context of the Cu-Mo-S interrelationship.


Effects of severe energy and protein deficiencies on the fibres and nuclei in skeletal muscle of pigs. 1. Measurements have been made of the size and number of muscle fibres and number of nuclei in a small indicator muscle (m. flexor digiti V brevis) in the fore-foot of the pig. Well-nourished, 10-d-old and 1-year-old animals were studied, as well as 1- and 2-year-old animals that were severely energy-deficient and protein-deficient. 2. The normal 1-year-old animals had much larger muscle fibres, with more nuclei, than the pigs in any of the other groups. 3. There were no significant differences between the numbers of fibres in the muscles of pigs in any of the four groups. 4. There was a significant difference between the number of fibres in the muscles of pigs coming from different litters, irrespective of their dietary history after birth. This suggests that the number of fibres is determined genetically before birth, and all that can take place after birth is an alteration in size.


New inhibitors of methane production by rumen micro-organisms. Development and testing of inhibitors in vitro. 1. A procedure is described for assaying in vitro the activity of various inhibitors of methane production by rumen micro-organisms. 2. Methods of preparation of various inhibitors are described together with attempts to characterize these compounds by determining their physical properties (physical state, density, chromatographic behaviour), their hydrolysis by rumen contents and their relative potency as inhibitors. 3. The results of preliminary studies with trichloroethanol and its ester with pivalic acid are given. 4. The inhibitory activities of several groups of related compounds are reported. These include the polyhalogenated alcohols and their esters with pivalic acid, the esters of trihalogenated alcohols and monobasic fatty acids from C2 and C16 and the trihalogenated alcohol esters of dibasic acids. The results of experiments with esters of alcohols and polyhalogenated carboxylic and sulphonic acids are also given. 5. It is concluded that the mechanism of action of the inhibitors might be similar to that of known polyhalogenated methane analogues (e.g. chloroform). The relative activity of various compounds might be partly governed by the ease of their absorption into the microbial cells and by the extent to which the esters can be hydrolysed by rumen contents. 6. The results show that some substances are very poor inhibitors, unless they are esterified (e.g. trichloroacetic acid) but on the whole the esters in which the polyhalogen grouping is on the alcohol portion of the molecule are better inhibitors than those in which it is on the acid portion of the molecule.


New inhibitors of methane production by rumen micro-organisms. Experiments with animals and other practical possibilities. 1. Two inhibitors of rumen methane production were given to sheep and their effects were measured using an in vitro technique. 2. The substances used were trichloroethyl pivalate (TCE-P) and trichloroethyl adipate (TCE-A). In one experiment with two sheep TCE-P was injected into the rumen and in another experiment with two sheep the same inhibitor was mixed with the food just before feeding. In another experiment, TCE-A was given to two sheep at two dose levels, and in an experiment with four sheep two levels of inhibitor and two levels of diet were used. 3. In general the inhibition of methane production was greater with samples of rumen contents taken after feeding than with those taken before feeding. When sheep were given 120--300 mg TCE-P/d the inhibition of methane production ranged from 21 to 81%. When sheep given maintenance rations were given 125-300 mg TCE-A/d there was 28--90% inhibition of methane production. When sheep were given twice maintenance rations 150 mg TCE-A/d gave no inhibition and 300 mg TCE-A/d gave very low inhibition of methane production (about 16%). 4. In most experiments there was a significant increase in the propionic acid:acetic acid concentration ratio in the rumen when methane production was inhibited. 5. The possible practical use of inhibitors is discussed.


Serum colloidal osmotic pressure in the development of kwashiorkor and in recovery: its relationship to albumin and globulin concentrations and oedema. 1. Serum colloidal osmotic pressure was measured in children 'at risk' to kwashiorkor, in other with frank signs of the disease and during recovery. Simultaneous estimations of serum albumin and globulin concentrations and assessments of the extent of oedema were also made. 2. During the development of kwashiorkor, serum colloidal osmotic pressure did not decrease significantly until albumin concentration was 25-1--27-5 g/l. Above 30-0 g/1, colloidal osmotic pressure was maintained at normal levels during which time a significant reciprocal relationship existed between albumin and globulin concentrations. These findings provide support for suggestions that there may be on oncotic regulation of albumin synthesis. 3. Low albumin concentrations were mainly responsible for the low colloidal osmotic pressures found in children with kwashiorkor and in agreement and previous findings the threshold for the formation of oncotic oedema was found to be about 2-35--2-65 kN/m2. 4. Values for colloidal osmotic pressure calculated from serum albumin and gobulin concentrations using emprical formulas did not agree well with measured values and no constant correction factor suitable over the whole range of albumin concentrations found in rural Ugandan children could be devised. In many hypoalbuminaemic children ony direct measurement of serum colloidal pressure will indicate the true extent of risk to an episode of oedema.


Some observations on the possible nutritional significance of vitamin B12-and folate-binding proteins in milk. Absorption of [58Co]cyanocobalamin by suckling piglets. 1. A study was made of absorption of [58Co]cyanocobalamin in suckling piglets. Cyanocobalamin given at birth and at 7 d of age was efficiently absorbed from the intestine and retained within the body, mostly in the liver. A 10 mug test dose was absorbed no less efficiently than 2-5 mug, despite the virtual absence of intrinsic factor in the gut. In piglets given a 10 mug test dose at different ages between 2-5 and 56 d, there was a marked decrease in the efficiency of retention between about 7 and 21 d of age. 2. Vitamin B12-binding capacity in the gastric muscosa increased with age, from 40 ng at birth to about 2000 ng at 14 d and 7000 ng at 35 d. This binder-protein was largely endogenous, whereas much of the unsaturated binder-protein in intestinal mucosa was apparently derived from milk. 3. The chyme in the stomach and small intestine contained unsaturated binder-protein, partly endogenous and partly deriving from milk, which prevented uptake of added [G-3H]-cyanocobalamin into the 'solids' phase of the intestinal contents. The intestinal chyme contained large numbers (log10 7-0--9-1/ml) of bacteria, some of which were isolated and shown to take up cyanocobalamin or folic acid or both. 4. The finings are discussed in relation to the concept that for some days or wekks after the cessation of transport of inact protein across the neonatal gut epithelium ('closure'), protein-bound vitamins may continue to be taken up into the epithelial cells and there released for transport into the circulation. It is concluded that unsaturated vitamin-binders may strongly influence the ecology of the intestinal microflora.


Metabolic studies of [75Se]selenocystine and [75Se]selenomethionine in the rat. 1. The long-term fate in rats of an oral dose of [75Se]selenocystine was compared with that of an oral dose of [75Se]selenomethionine. 2. Urinary and faecal radioactivities were measured during the 1st week and whole-body radioactivity was determined for 10 weeks. Rats were killed at weekly intervals for 4 weeks and at weeks 6 and 10 for analysis of tissue distribution of 75Se. 3. Intestinal absorption of [75Se]selenocystine was 81% of the administered dose; that of [75Se]selenomethionine was 86%. Urinary excretion of absorbed [75Se]selenocystine was 13-9% and that of [75Se]selenomethionine was 5-8% in the 1st week. 4. Whole-body retention of 75Se was greater for [75Se]selenomethionine than for [75Se]selenocystine but after the 1st week it decreased at a similar rate in both groups. Tissue distribution of retained 75Se was also similar in both groups. 5. The initial utilization of [75Se]selenocystine was different from that of [75Se]selenomethionine. However, after the 1st week 75Se from both sources appeared to be metabolized similarly, suggesting that dietary Se of both forms is ultimately incorporated into the same metabolic pool. 6. When these findings were compared with those of earlier studies with [75Se]selenite and 75Se incorporated in vivo into rabbit kidney (RK-64Se) (Thomson, Stewart & Robinson, 1975) the metabolism of [75Se]selenocystine resembled that of [75Se]selenite and RK-75Se, rather than that of [75Se]selenomethionine.


A dietary survey of older people in Edinburgh. 1. Dietary histories covering 1 week were obtained from 212 men and 263 women, aged 62--90 years, who formed a random sample of the older people living in a defined area of Edinburgh. The histories were validated by 2 d weighed-diet records for 219 of the subjects. 2. Nutrient intakes are given as mean values and standard deviations, and as percentage distributions of intake relative to the recommended intakes of nutrients. Intakes are also related to factors which might affect diet adversely. 3. Mean values obtained suggested that intakes were less than recommended intakes for more nutrients for women than for men, particularly values for energy and vitamin D. Values for percentage distributions indicated  that a substantial proportion of all subjects had low intakes of ascorbic acid and vitamin D, that the energy intake of many women was low and that for most nutrients a greater proportion of men than of women had the recommended intake. Factors assocIATED With significant proportions of subjects with less than the recommended intakes were mental illness in women and deafness and severe dyspnoea in men. 4. Possible action to improve the diet of the elderly is discussed.


Effect of phase transition on the kinetics of dye transport in phospholipid bilater structures. Binding of 8-anilino-1-naphthalenesulfonate to dimyristoyl-L-alpha-lecithin bilayers enhances the fluorescence quantum yield of the dye molecule by 100-fold. By following the generation of fluorescence after a rapid mixing in a stopped-flow apparatus (mixing time 2 msec), kinetics of the binding of the fluorescence probe to the phospholipid vesicles has been investigated in the temperature range where the crystal-liquid crystal phase transition of the bilayer structures occurs. No reactions depending on the dye or the vesicle concentrations were detected. This suggests that the initial adsorption of the dye was very rapid. Two kinetic phases which appear in the 50 msec and the second time ranges are unimolecular. The faster one has a small amplitude and is observable in the entire temperature range studied. In the phase transition region the slower reaction becomes the major kinetic phase. It also increases the apparent concentration of bound dye by a factor of 2. These observations suggest that the 50-msec reaction has detected a reorientation of the probe molecule after the initial binding, and that the slow reaction represents a transport of the dye molecule into the inner layer of the lipid vesicle. The transport reaction is extremely temperature sensitive and exhibits a maximum rate at the midpoint of the bilayer phase transition (Tm = 24.1 degrees). the Arrhenius plot of the transport reaction shows a maximum at the Tm. the same temperature dependence was also observed for the bromothymol blue transport reaction. However, no such effects were detected for less amphiphilic molecules such as tetracycline, chlortetracycline, and pyrene. In the latter systems only a slight bending of the Arrhenius plots were seen at the phase transition temperature. Since the kinetics of the transport of 8-anilino-1-naphthalenesulfonate is sensitive to the physical state of the phospholipid bilayers this reaction may be used for probing membrane structures.


Transport of 8-anilino-1-naphthalenesulfonate as a probe of the effect of cholesterol on the phospholipid bilayer structures. The transport of 8-anilino-1-naphthalenesulfonate in dimyristoyl-L-alpha-lecithin bilayers has been found to be extremely sensitive to the crystalline state of the phospholipid dispersions. Thus this reaction may be used for probing the membrane structures. In binary mixtures of cholesterol and phospholipid the fluorescence enhancement of the dye completely disappears when the mole fraction of cholesterol reaches 33%. At temperatures below and above the phase transition of the lipid bilayers, the rate of the probe transport increases significantly in the binary mixtures. It reaches a maximum at 17 mol % of cholestero. The rate at this cholesterol content approaches the maximum value obtained for the probe transport in pure phospholipis, e.i., the rate at the midpoint of the phase transition. These observations indicate that the effect of cholesterol in the phospholipid dispersion is to maintain the bilayer structure close to the melting temperature of the lipid phase transition. In other words, cholesterol may be an effective buffer for membrane crystalline state when its concentration is near 17 mol %.


Reaction of 1,3-bis(2-chloroethyl)-1-nitrosourea with synthetic polynucleotides. The antitumor agent BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) was incubated with poly(C) and poly(G) in aqueous solution at 37 degrees and pH 7 to produce approximately 0.33 and 0.07% substitution, respectively. Under the same conditions, there was relatively little reaction with poly(A) and poly(U). Poylnucleotides reacted with [14C]BCNU were digested by chemical and enzymatic methods, and the derivative nucleotides were isolated by column chromatography. There were identified by a combination of ultraviolet and mass spectroscopy as 3-(beta-hydroxyethyl)CMP, 3,N4-ethano-CMP, and 7-(beta-hydroxy-ethyl)GMP. This would indicate that BCNU generates active two carbon fragments, probably chloroethyl carbonium ions, which are free to react with nucleotides. The production of these substituted bases may be important to the mechanism of action of the therapeutic nitrosoureas since they would probably alter the function of any nucleic acid which contained them.


The transmembrane proteins in the plasma membrane of normal human erythrocytes. Evaluation employing lactoperoxidase and proteases. The molecular architecture of the human erythrocyte membrane has been probed using lactoperoxidase-catalyzed iodination in conjunction with Pronase hydrolysis. Resealed, hemoglobin-free ghosts were labeled at the cytoplasmic surface and the external membrane surface was subsequently digested with Pronase. Changes in size of the components labeled at the cytoplasmic surface were readily detected by sodium dodecyl sulfate gel electrophoresis. The protein 3 molecular weight class labeled at the cytoplasmic surface was extensively hydrolyzed at the external surface to produce a major 65000 molecular weight fragment and a minor 45000 molecular weight fragment. When resealed membranes were labeled on the external surface the same 65000 molecular weight labeled component is produced. These results unequivocally demonstrate that the same polypeptides in the protein 3 molecular weight class that can be labeled by lactoperoxidase at the cytoplasmic membrane surface are digested by Pronase at the external surface and are, therefore, transmembrane components. Where it is possible to label one surface of a membrane with lactoperoxidase and reseal the membrane this procedure represents an alternate method for establishing transmembrane configuration of membrane proteins.


The isolation and structure of the core oligosaccharide sequences of IgM. Methods are presented for separating the three IgM heavy chain sialoglycopeptides associated with asparagines 170, 332, and 395. The core glycopeptide units containing the disaccharide fucosyl-N-acetylglucosamine were obtained through the use of an endo-beta-N-acetylglucosamindase from Diplococcus pneumoniae, following exoglycosidase treatment of the sialoglycopeptides. In addition to the core glycopeptides, high yields of a tetrasaccharide, (Man)3GlcNAc, were obtained. The fucose in the core disaccharide is glycosidically linked to the 6-O position of the N-acetylglucosamine residue in Asn-GlcNAc. This core unit is resistant to glycosyl asparaginase, but becomes susceptible to hydrolysis on removal of the fucosyl residue by a purified hen oviduct alpha-L-fucosidase. The core sequence of the immunoglobulin M sialoglycopeptides appears to be similar to that of most other asparagine-linked oligosaccharides in consisting of a basic unit composed of beta-D-Man-(1 leads to 4)beta-D-GlcNAc(1 leads to 4)beta-D-GlcNAc(1 leads to 4), but with L fucose linked alpha-(1 leads to 6) to the proximal GlcNAc. The two nonreducing terminal ends of (Man)3GlcNAc are linked to beta-D-Man by alpha-(1 leads to 3) and alpha(1 leads to 6) bonds, respectively.


Mechanism of action of adenosylcobalamin: 3-fluoro-1,2-propranediol as substrate for propanediol dehydrase--mechanistic implications. 3-Fluro-1,2-propanediol has been found to be a substrate for propanediol dehydrase and has very similar binding and catalytic constants compared to the natural substrate. The only isolable products of the reaction are acrolein and inorganic fluoride; with 3-fluoro-3,3-dideuterio-1,2-propanediol as substrate, only 3,3-dideuterioacrolein is obtained. These results indicate that the primary product of the reaction is 3-fluoropropionaldehyde which spontaneously loses hydrogen fluoride to yield acrolein. The similar kinetic parameters for the fluorinated as compared to the normal substrate suggest that significant charge does not develop on the fluorinated or, by implication, the natural substrate during any rate-limiting steps of the reaction. These results support a radical, as contrasted to an ionic pathway for reactions involving adenosylcobalamin and diol dehydrase.


Studies on the generation of hydrogen peroxide during some non-enzymic reactions changing the hyaluronic acid molecule. The effect of catalase on non-enzymic-induced changes in the conformation of hyaluronic acid in a vitreous humour preparation was measured using viscometry. Ascorbate, heavy metal ions, riboflavin or EDTA all lowered the viscosity of hyaluronic acid solutions. These effects could be prevented by the addition of catalase. This suggested that H2 O2 is produced by these compounds and that the resulting change in conformation of hyaluronic acid may be due to peroxyl and hydroxyl attack by the free radicals thus generated.


Effects of external osmolality on polyamine metabolism in HeLa cells. The polyamine content of Escherichia coli is inversely related to the osmolality of the growth medium. The experiments described here demonstrate that a similar phenomenon occurs in mammalian cells. When grown in media of low NaCl concentration, HeLa cells and human fibroblasts were found to contain high levels of putrescine, spermidine, and spermine. The putrescine content of HeLa cells was a function of the osmolality of the medium, as shown by growing cells in media containing mannitol or additional glucose. External osmolality per se had no effect on the contents of spermidine and spermine. For all media, the total cellular polyamine content could be correlated with the activity of ornithine decarboxylase, the first enzyme in polyamine biosynthesis. Different levels of enzyme activity appear to result solely from variations in the rate of enzyme degradation. A sudden increase in a NaCl concentration produced rapid loss of ornithine decarboxylase activity and a gradual loss of putrescine and spermidine. A sudden decrease in NaCl concentration led to rapid and substantial increases in ornithine decarboxylase activity and putrescine.


Uptake of proteinase-alpha-macroglobulin complexes by macrophages. Complexes of labelled proteinases (subtilopeptidase A, trypsin) with serum alpha 1-macroglobulin or alpha 2-macroglobulin are rapidly taken up in vitro by rabbit alveolar macrophages and peritoneal macrophages but not by mixed rabbit peripheral blood leukocytes. Enzyme, not bound to alpha 1- or alpha 2-macroglobulin, does not become associated with alveolar macrophages. Chemically inactivated subtilopeptidase A does not bind to alpha 1- or alpha 2-macroglobulin; chemically inactivated subtilopeptidase A in mixtures with alpha 1 - or alpha 2-microglobulin, does not interact with alveolar macrophages. Blocking experiments confirmed that the interaction of proteinase with alveolar macrophages is complex specific; uptake of labelled complex was prevented by the simultaneous addition of macroglobulin complexes formed with non-labelled subtilopeptidase A, subtilopeptidase B, trypsin or chymotrypsin but not by macroglobulin alone. The findings demonstrate a complex-specific interaction between proteinase-alpha-macroglobulin complexes and macrophages.


Cellular energy dependent agglutination of rat ascites tumor cells mediated by concanavalin A and Ricinus communis agglutinin. Effect of various metabolic inhibitors on the agglutination of rat ascites tumor cells mediated by concanavalin A and Ricinus communis agglutinin was studied using a quantitative assay method for agglutination in which turbidity of cell suspension is measured. Cell agglutination was inhibited by low temperature, cytochalasin B and inhibitors of energy generating systems without affecting lectin binding, and agglutination was not affected by hydroxyurea, actinomycin D or cycloheximide. The inhibitors of energy generating systems decreased the cellular ATP level and inhibited macromolecular synthesis under the conditions where they inhibited the agglutinations. In contrast, cytochalasin B did not depress the cellular ATP level nor inhibit RNA and protein syntheses. These results suggest that the agglutination is associated with cellular energy dependent processes other than macromolecular synthesis; probably with some cellular surface movements participated by microfilament activity.


Biochemical and cytological studies of mitochondrial development in chloramphenicol-induced rice coleoptiles. The ultrastructure and respiratory activity of mitochondria in rice coleoptile grown in the presence and in the absence of an inibitor of mitochondrial protein synthesis (chloramphenicol) have been studied. It is shown that during the first 48 h of germination a rapid development of mitochondrial cristae takes place without notable influence of chloramphenicol on biogenesis of mitochondria. But the presence of the inhibitor has a significant effect in the subsequent period (48-144 h): a gradual and almost complete reduction of mitochondrial cristae is observed. These unusual "noncristate" mitochondria, although greatly lacking cytochrome oxidase, have a high respiratory activity. The respiration of "noncristate" mitochondria is resistant to KCN. It is supposed that chloramphenicol-induced rice coleoptile can be used as a new convenient object for studies of the nature of alternative oxidase as well as the biogenesis of mitochondria with cyanide-insensitive respiration.


Peptidoglycan compositions of a new strain of Arthrobacter crystallopietes during sphere-rod morphogenesis. Arthrobacter crystallopoieties ATCC 15481 was used to isolate a new strain. designated Arthrobacter crystallopoieties EPSR-16, which had a mass doubling time in brain heart infusion broth and in glucose/salts/yeast extract medium of 30 min compared to 2.40 h for the parent strain in similar media. The growth rates for the new strain and for the parent were close to 12 h in glucose/salts medium. The new strain formed well-separated cocci and diplococci in glucose/salts medium, and upon nutrient shift-up all the cells in the population gradually changed into well-separated rods of regular shape. In the spherical state the cell wall peptidoglycan of the new strain contained lysine and no diaminopimelic acid. A gradual loss in lysine and a gain in diaminopimelic acid occurred during morphogenesis. Diaminopimelic acid became predominant in the cell wall during balanced growth in the rod state.


Small copper-binding proteins from normal and copper-loaded liver. The same three low molecular weight copper-binding proteins which have been purified from the soluble fractions of Cu2+-loaded livers (200 mug Cu2+ per g wet weight) were also found to be present in livers of normal rats (4 mug Cu2+ per g wet weight) but in much smaller quantities. Therefore, Cu2+ loading enhances the amount of preexisting proteins rather than inducing the synthesis of new proteins. Amino acid analyses of each of the three showed them to be different from the metallothioneins which are present on loading with other trace metals including Cd2+ and Zn2+.


[Rheological studies of interphase adsorption layers of lysozyme at phase separation liquid boundaries]. Rheological studies of thin layers of biopolymers provide a principally new approach to the studies of the structure and functions of biomembranes. Rheological properties of interphase adsorption layers of lysozyme at different concentrations, temperatures and at the border with various carbohydrates. The values of moduli of fast elastic deformation E1s, slow elastic deformation E2s, equilibrium module of elasticity Es, viscosity of elastic aftereffect, plastic viscosity eta 0s and eta s for the interphase layers of lysozyme at liquid borders show that the interphase adsorption layers were solidlike, and the moduli of dimeric structure evaluated as volume ones correspond to the characteristics of normal elastomeres.


[Utraviolet adsorption and fluorescence of human thyroalbumin]. Some spectral properties of human thyroalbumin have been studied. Ultra-violet absorption of the aqueous solution of this protein has two maxima: at the wavelengths of 276 and 296--298 nm. Under the excitation by a monochromatic light with the wavelength of 280 nm the thyroalbumin has the fluorescence spectrum with the maximum at 430 nm and the quantum yeild of fluorescence about 5,4%. It has been established that thyroalbumin fluorescence consists of two components with the maxima at 385 and 450 nm. Moreover the "sortwave" component is principally attributed for by the presence do iodoamino acids.


[Kinetics of the interaction of ferrous oxide with oxidized lipids and possibility of chiluminescent determination of hydroperoxides]. The theory shows that for lipids containing hydroperoxides of unsaturated fatty acids there exists a verge concentration of Fe2+: at concentrations of Fe2+ lower than the verge one the peroxidation process develops autocatalytically and at higher concentrations it looks pulseshaped. In the second case the amplitude of pulse concentration of peroxide radicals and the square root from the maximum value of chemiluminescence intensity are proportional to the concentration of hydroperoxides present in the system at the time of ferrous ions injection. The former two values do not depend on the concentration of inoxidized fatty acids. In the experiments of chemiluminescence of partially oxidized linoleic acid and lecithin in methanol-benzene solutions (1 : 2) a perfect correlation between the experimental data and theoretical conclusions was revealed.


[Elemental analysis of biological objects by characteristic x-ray radiation excited by protons]. The results of the analysis of white mouse blood according to characteristic X-radiation (CXR) stimulated by the protones with the energy of 2,5 Mev are presented. CXR was recorded by spectrophotometry on the basis of siliceouslithium detector with energetic resolution of 260 ev by the generator of the exact amplitude and 290 ev along the line of 6,4 kev Co57. Sensitivity (3 divided by 5)-10(-8)g was reached. The analysis according to CXR permits to reveal microelements in the quantities 10(-10)--10(-12) g. Small quantities of the substance are required.


[Cell molecular computer. VIII. Possible construction of a molecular memory in biological membranes and principle of minimum expenditures of free energy in recording information]. The principle of minimum expenditure of "price of action" [5] provides in the liquid cell membrane such operative memory which uses for recording information from any receptor (multidigit number) the transmission of an electron with the loss smaller than 250 mev. According to the hypothesis such memory is constructed from equal protein molecules and different lipid addresses for different receptors. It works on Brown collisions, weak interactions between the molecules and capture bonds controlled by MCC with a minimum expenditure of free energ- for the formation and breakage of bonds.


[Photodissociation of carboxyhemoglobin with different degrees of saturation]. The graphical method is suggested and treated for obtaining of the binding curves in photodissociation conditions. Some kinetic properties of photolisis of HbCO are discussed in connection with sharp increase of free gase concentration in solution.


[Free-radical oxidation of biological membrane lipids. VI. Nature of linoleic acid chemiluminescence]. An original scheme of chemoluminescence of unsaturated fat acids is suggested on the basis of analysing the kinetics of peroxide formation, chemoluminescence and fluorescence of linole acid. The agreement of the model with literature and our own experimental data is shown by the method of analogue modelling.


[Phosphorescence of octaethylchlorine, isobacteriooctaethylchlorine and their metal complexes]. The phosphorescence of dihydrooctaethylporphin (octaethylchlorin or OEC), of its complexes with magnesium, zinc, copper and palladium, and of zinc and palladium complexes of isobacteriooctaethylchlorin (5,6,7,8-tetrahydrooctaethylporphin with adjacent hydrogenated pyrrole rings or THOEP-ADJ) has been investigated. The phosphorescence spectra and phosphorescence excitation spectra as well as the ratio of fluorescence and phosphorescence yields and the triplet state lifetume have been measured. It has been shown that the singlet-triplet interval is about 4100 cm-1 for OEC complexes and about 4300 cm-1 for THOEP-ADJ complexes, and depends wealky on the nature of the metal atom forming the complex. The triplet level position of chlorophyll alpha is discussed. It is concluded that the maximum of chlorophyll alpha phosphorescence spectrum must be located at 895 nm.


[Comparative study of membrane-bound acetylcholinesterase in guinea pig and rabbit brains]. As a result of kinetic studies on acetylcholinesterase inhibition by allosteric effector d-tubocurarine it was shown that interaction between modifier and catalytic sites of rabbit and guinea pig acetylcholinesterase are different for these two species. Judging by the inhibition curves and sensitivity of d-tubocurarine theses differences involve enzyme microenvironment in the membrane. Addition to 7,15-10-6 M d-tubocurarune to solubilized preparation led to a significant fall in the value of Hill coefficient for enzyme-substrate interaction. This may be indicative of the changes in the conformational state of the enzyme after its dissociation from the membrane, i. e. of the membrane structure role in the formation of the structural and functional enzyme properties.


[Instability and excitation propagation in a catalytic reaction model. I. Model of a system with concentrated parameters]. Using peculiarities of oxidative-rastorative catalytic reactions the system of nonlinear differential equations has been obtained. Pecularities of the behaviour of the system on phase plane of variables at different parameters are considered. The system may be autooscillative, trigger, waiting. Problems of model application in membrane, quantum, enzymatic systems are discussed.


[Honeybee phonoreceptors].

[Honeybee phonoreceptors]. Bee phonoreceptors are revealed by electrophysiological method. These are hair sensillae located between facet eyes and occipital commissure. The region of the highest sensitivity of receptors in within the range of the maximum energy of various sound signals used in the communication of bees. The receptors exactly distinguish the signals according to their duration and intensity.


[Relation of the birefringence of a bilayer lipid membrane to the ionic strength of the medium]. A direct method of measuring the optical phase difference arising in a bilayer lipid membrane at the expence of its birefringent properties is offered. A dependence of the value and sign of lipid bilayer birefringence on ionic concentration in the medium has been observed. For example, the birefringence value of the bilayer from egg lecithin with eta-decan changes from -0.005 to 0.01 with a change of NaCl concentration from 0 to 5 M, the sign changing at about 1 M. It is suggested that the polar region of the bilayer has negative birefringence, and that it is its infrastructure that changes with the ionic strength of the solution.


[Comparison of the energy characteristics of Acetabularia membranes in light and darkness]. Energetic parameters of the membrane of marine alga Acetabularia were compared at light and dark during the action potential (AP). Direct current resistance of the resting membrane at dark as well as at light is of the order 1000-5000 omega-cm2 without considerable difference. The maximum resistance of the excited Acetabularia membrane is somewhat increased at dark as compared to its value at light. The maximum power of the membrane system and that of its regulating mechanism along with the energy dissipating AP at light exceed the same values at dark. The dissipating energy and the work Acetabularia cell performs during the AP are also compared for light and dark conditions.


[Mathematical model of the cytokinetics of erythropoiesis in mouse bone marrow and spleen]. The described model approximates the function of the erythropoietic system of the mouse to the function of a self-renewed cellular system, describable in the terms of cell population kinetics. The model is based on a number of experimentally proved ideas of contemporary haematology and arises from the assumption that there exists mutual negative influence between the cellular populations of the bone marrow and spleen. Considering the erythropoietic system in the mouse to be composed of two relatively independent parts - the bone marrow and spleen - the described model differs from the attempts so far made on the mathematical modelling of erythropoiesis.


[Electrophoresis of chloride ions and changes in the membrane potential of energized mitochondria]. In energized rat liver mitochondria the simultaneous H+, K+ and C1- transport was studied by corresponding ion selective electrodes. It was shown that the C1- transport induced by valinomycin, by valinomycin plus carbonyclyanide m-chlorophenylhydrazone was governed by the membrane potential. It is suggested that observed in energized mitochondria the C1- electrophoresis may servt as an indicator of membrane potential changes.


[l model of a leading center].

[l model of a leading center]. Periodic solutions are obtained for the distributed model of the excitable medium concerned with the decay of stopped excitation fronts. Such solutions make it possible to consider the initiation of the leading centres in a excitable medium.


[Rate of excitation propagation in a reduced Hodgkins-Huxley model. I. Rapid relaxation of the sodium current]. The question of calculating excitation propagation velocity is analyzed on the basis of the Hodgkin-Huxley model. The activation of the sodium current is assumed to be rapid as compared to the rate of potential variation. Because of slow variation of potassium activation and sodium inactivation the dynamics of these processes is assumed to be of negligible effect in the region of impulse velocity formation. By means of pieace-wise linear approximation of thus obtained voltage-current characteristics the characteristics the analytical solution of the problem was found. In two limiting cases this solution coincides with the solutions of Kolmogorov and Scott. The dependence of impulse velocity on parameters is analyzed and illustrated graphically.


[Rate of passive conduction in lattice structures]. A mathematical model of passive conduction in syncitial symmetric structures is considered. Explicit formulae of the dependence of a decrease of stationary solution and of electrotonic conduction velocity are obtained.


[Anisotropy of stationary rates and delays in extrasystolic waves in the dog heart]. Excitation propagation in the ventricle and auricle bands of the dog's myocardium has been studied. The anisotropy of stationary valocities and delays of the initiation of extrasistole exciation has been shown: along the fibres the velocity is higher and the delay smaller than across the fibres. The levels of anisotropy of velocities and delays are almost equal in each structure. The strongest anisotropy of delays and velocities (-4,5) is observed in the ventricle muscle layer; the weakest (1,7)-in a specialized layer. The anisotropy of velocities and delays is the greater, the greater is the electrotone anisotropy. A new mechanism of extrasistole initiation (reentry) in the system homogenous by the membrane properties, but with anisotropy of intercellular bonds is considered.


[Integral characteristics of the cardiac electrical excitation wave]. A set of characterisitics of the cardiac electrical generator is described which expresses in an integral form some important properties of the electrical excitation wave, in particular its summary intensity, average spatial localization and distinction from a uniform double layer with planar rim. Relation of the proposed model to the multipole equivalent generator is discussed, and procedures for computing its characteristics are given. Calculation results for these characteristics on the basis of experimentally measured electrical field potentials of isolated dog hearts are presented.


[Kinematics of metachronous walking. II. Gaits]. For an arbitrary locomotory system three ways of gait classification are considered and compared. A general classification is represented as an "abstract scheme" of phase-space separation of the locomotory system. The "configurational scheme" is the result of methachronal coordination postulate, and the "footprint scheme" is the result of the postulating of special properties of the footprint track.


[Analysis of a control system for speech movements]. Analyzing the control quality in autonomic contour of articulation control system an account is made for the nonlinearities of the type of the zone ofunsensitivity, limitation and logarithmic response of the receptor. Regions of stablity and autooscillation frequency are determined. The role of recontrolling value is stated as a criterion of the control quality. It is suggested that the mechanisms of some stammering forms are concerned with the initiation of autooscillations in the articulation control system.


[Model representation of rat motor behavior during electrical self-stimulation of the brain. I. Brief review of experimental data. Formal model]. The stimulation of the brain in self-stimulation situation activated the motor behaviour. The activity of the motor behaviour versus duration of the movements which define the motor activity is a decreasing function. The effect of stimulation versus duration or the strength of stimulation is an increasing function. The solutions of equation having made after comparing these two functions demonstrate the relations between the motor behaviour and stimulation parameters.


[Efficiency of dolphin auditory perception in relation to time characteristics of the signal]. Experimental data are presented on evaluating the efficiency of auditory perception of the dolphin Tursiops truncatus of tonal signals of different duration and of the fixed energy on the background of Gauss obstacle. The dependence of percepting properties on time characteristics of the signal are stated. A comparative analysis of the efficiency of dolphin auditory system with that of the coordinated filter is carried out. Biological receiving systems are shown to be adaptive. The self-tuning linits of the dolphin auditory system at a given level of the possibility of correct detection are determined.


[Hysteresis and multiplicity of dynamic states in open 2-substrate enzyme reactions with substrate inhibition]. A mathematical model of an open two-substrate enzymic with substrate inhibition has been analyzed. The hysteretic form of the reaction input characteristics resulting in the appearance of three alternative stationary states, O1, O2 and O3, has been obtained. The region of existence of a stable limit cycle has been determined within the framework of linear approximation. Analysis of the model to a non-linear approximation shows that close to the boundary of the stability region the unstable or stable limit cycle can surround O1 or O3 as well as the only stationary state O.


Effect of heat treatment on the elasticity of human erythrocyte membrane. A parallel plate flow channel is employed to study the effect of heat treatment on the elasticity of human red cell membrane. An irreversible transition between 46 degrees C and 50 degrees C results in an approximately 200% increase in an elastic constant measured at 25 degrees C. This transition is attributable to irreversible protein denaturation which has been shown by other to occur at similar temperatures in calorimetric studies of red cell ghosts.


Water exchange between red cells and plasma. Measurement by nuclear magnetic relaxation. Water exchange between human red blood cells and the plasma phase was measured by water proton nuclear magnetic resonance relaxation in the presence of low concentrations of Mn(II) and by 17O relaxation of H217O in the absence of added Mn(II). The results were analyzed as a classic case of two-compartment exchange. The half-life for cell water at 25 degrees C was found to be 15 ms +/- 2 ms, longer than the time determined by other techniques. The T1 of the hemoglobin protons in the red cell and the volume of exchangeable water were also measured. The method appears to be a sensitive tool for the study of membrane permeability to water and other small molecules undergoing rapid exchange.


Further studies of activation-inactivation coupling in Myxicola axons. Insensitivity to changes in calcium concentration. In Myxicola axons subjected to moderate depolarizations the sodium inactivation time constants obtained from the decay of sodium current during a maintained depolarizatin (TSh) are substantially smaller than inactivation time constants determined at the same potential from the effect of changes in the duration of conditioning prepulses (Tph). This report extends these observations to positive membrane potentials and demonstrates that for sufficiently large depolarizations TSh and Tph become comparable. The ratio of inactivation time constants, Tph/TSh, is unaffected by changes in [Ca++] provided total divalent cation concentration is maintained constant, while changes in total divalent ion concentrations produce simple voltage shifts comparable to those obtained from measurement of membrane sodium or potassium conductances. Sodium inactivation delay was quantitatively determined as a function of membrane potential, and found to be similarly unaffected by changes in [Ca++] at constant total divalent ion concentration. Inactivation delay is, however, directly proportional to the activation rate constant over a wide range of potentials.


Tilted hydrocarbon chains of dipalmitoyl lecithin become perpendicular to the bilayer before melting. Differential scanning calorimetry studies of dipalmitoyl lecithin show two reversible transitions as the temperature is changed between 20 and 50 degrees C. A pretransition endotherm occurs at 35 degrees C prior to the main chain melting endotherm which occurs at 42 degrees C. X-ray diffraction studies show that below 33 degrees C the chains of the lecithin are fully extended, packed in a hexagonal crystalline lattice but tilted with respect to the plane of the bilayer. Between 35 and 42 degrees C the chains are similarly packed but oriented perpendicular to the bilayer plane. Above 44 degrees C the chains are "melted" or disordered. Monolayer studies of dipalmitoyl lecithin using continuous recording of pressure with molecular area reveal the existence of two solid condensed phases corresponding to these tilted and verticle chain structures. The tilted to perpendicular transition would account for the pretransition endotherm of the lipid; the crystalline to melted change corresponds to the larger transition observed at 42 degrees C.


An electron spin resonance study of synaptosome opiate receptors. The preparation and use of a spin labeled morphine. Morphine spin labeled on the phenolic hydroxy group has been prepared using commercially available reagents and characterized by thin layer chromatography, mass spectroscopy, and electron spin resonance spectroscopy. It has been shown that morphine modified in this way retains some opiate activity, does not pass through the blood-brain barrier, and specifically binds to isolate rat brain synaptosomes. Spin labeled morphine has been shown to be an effective biophysical probe complementing radioactive tracer techniques in the study of the narcotic receptor site.


Rapid changes in intracellular free calcium concentration. Detection by metallochromic indicator dyes in squid giant axon. The metallochromic indicator dyes, arsenazo III and chlorophosphonazo III, were used in squid giant axons to detect rapidly the very small influxes of calcium that occur as a result of changes of membrane potential.


Thermophilic microbiological treatment of high strength wastewaters with simultaneous recovery of single cell protein. Simultaneous removal of organic materials and recovery of protein in the form of bacterial cells from a simulated high strength biodegradable wastewater was studied using thermophilic aerobic microorganisms. A naturally occurring mixed culture of thermophilic microorganisms was obtained from soil, wastewater, hay, silage, etc. A chemically defined medium containing glucose along with other essential nutrients was employed as the feed. The kinetic behavior of the culture was studied in a continuous culture at an optimum temperature of 58 degrees C. Studies were were also performed on the effects of solids retention time (SRT) on the observed cell yield and the protein and ash content of the harvested biomass. An economic analysis of the process for single cell protein recovery was given.


Carpal and tarsal osteolysis.

Carpal and tarsal osteolysis. A 19-year-old girl with carpal and tarsal osteolysis has been presented. The clinical course was characterized by normal early growth and motor development followed by the insidious onset in early childhood of a progressive, peripheral joint destruction, especially in the tarsal and carpal bones. The patient's course was complicated by acquired spasticity from platybasia, scoliosis, generalized muscle weakness, mild growth failure and corneal clouding.


The Achard syndrome.

The Achard syndrome. The Achard syndrome is a well-defined clinical entity consisting of widespread dysostoses and increased ligament laxity. The bony involvement appears most consistently in the tubular bones of the hands and feet, the mandible and the calvarium, but may also be noted elsewhere in the body. Hypermobility and subluxations of the joints, increased lateral excursion of the patellas and other findings reflect the increased ligament laxity.


A study of the flexor digitorum superficialis tendon in flexion and extension at the proximal interphalangeal joint. Using a physical model to represent the detailed morphology of the flexor digitorum superficial tendon, the functions of the fibrous arrangement of this tendon in the human fingers were studied for flexion and extension of the proximal interphalangeal joint. In extension of the joint, the fibrous pattern acted as a dynamic ligament for the joint. In flexion, the arrangement of fiber bundles of the tendon contributed to tha balanced distribution of forces across the joint's surfaces and for mechanical interplay with the deep long flexor tendon in the region of the joint.


Rupture of the tendo achilles: another diagnostic sign. A new sign had been described--the knee flexion test which when used together with other well recognized tests, will help in the diagnosis of rupture of the tendo Achilles. Each of these tests is described as to their presence in both acute and old ruptures of the tendo Achilles.


Articular muscle of the knee--articularis genus. Articularis genus has been considered by many as a part of the quadriceps muscle. Our observations have confirmed our opinion that this is a separate and distinct muscle. It is always present and has a discrete origin and insertion. This muscle has a very important function to perform. It elevates the capsule and the synovial membrane of the knee joint and prevents them from being pinched during extension of the leg. Thus it plays a very important role in the erect posture of humans.


Simulation of cell behavior: normal and abnormal growth. A mathematical model simulating a cell growing in a culture medium is obtained. Using this model, various behavioral patterns of the cell are obtained under different types of disturbances, in particular when (i) a Mg2+ deficiency experiment and, (ii) a split-dose ionizing radiation experiment are carried out, (iii) when disturbances on the rate constants of the biochemical reactions taking place in the nucleus of the cell are applied, and (iv) when the cell's interior components are perturbed. The cell model results obtained agree well with experimental results for the Mg2+ and split dose experiments, and explain the mechanism of the split dose radiation experiment without the need to introduce additional axioms (e.g. healing processes) into the dynamics of the cell. Conditions are obtained which cause the cell to behave in a rapidly growing 'tumor-like' mode; it is shown that once the cell moves into this 'tumor-like; mode, its behavior is irreversible, i.e. if a disturbance of opposite type is then applied to the 'tumor cell, the cell will not revert back to its original normal behavior.


A semi-empirical model for flow or blood and other particulate suspensions through narrow tubes. A semi-empirical model applicable to the flow of blood and other particulate suspensions through narrow tubes has been developed. It envisages a central core of blood surrounded by a wall layer of reduced hematocrit. With the help of this model the wall layer thickness and extent of plug flow may be calculated using pressure drop, flow rate and hematocrit reduction data. It has been found from the available data in the literature that for a given sample of blood the extent of plug flow increases with decreasing tube diameter. Also for a flow through a given tube it increases with hematocrit. The wall layer thickness is  found to decrease with increase in blood hematocrit. A comparison between the results of rigid particulate suspensions and blood reveals that the thicker wall layer and smaller plug flow radius in the case of blood may be attributed to the deformability of the erythrocytes.


Blood flow: theory, effective viscosity and effects of particle distribution. A study is made of blood flow by assuming that the blood constitutes a suspension of cells in plasma instead of a simple homogeneous fluid. A macroscopic theory governing the motion of plasma in a plasma-cell system is derived from the local volume averaging method for a system without mass transfer between the phases, and its characteristic length is much larger than the size of the cells. The equations governing the motion of the local averaged fluid quantities include one additional term in the equation of motion and two additional terms in the energy equation. These terms represent, respectively, the force exerted upon the fluid by the particles, and the rate of heat transfer and work kone upon the fluid by the particles. The theory is applied to obtain the effective viscosity as the explicit function of the volume concentration of the cells by assuming that the cells behave like rigid spherical particles with slip-collision, and the plasma is an compressible Newtonian fluid. Comparison with existing experimental results shows a good agreement. The theory is also used to obtain the effects of cell distribution upon the overall effective viscosity in a circular tube. The quantitative result shows that there is a decrease in overall effective viscosity as the concentration of cells increases toward the center of the tube, and the overall effective viscosity is smaller than the flow with evenly distributed cells.


Three dimensional laminar flow in distorting, axisymmetric, axially varying vessels. Three dimensional laminar, viscid flow is developed for Newtonian fluids which provides absolute values for axial, radial and tangential velocity fields everywhere if the dimensions of the vessel are known and two simultaneous axial velocities e.g. on and off the central axis in the same plane, and the central axis velocity gradient are measured. In addition, normal and shear stresses are determinable. The equation set satisfies gemoetric and other known flow limiting conditions such as no slip at surfaces etc. and are amenable for inclusion in general, dynamic flow expressions. Alternatively they may be used alone for certain problems involving gradients and secondary flows. A range of illustrations are shown for a distorting vessel with elliptic cross-section and small axial taper (analogous to the pulmonary trunk during ejection).


Construction, simulation, clinical application and sensitivity analysis of a human left ventricular control system model. A regulated left ventricular dynamics model is presented which involves interaction of the dynamics of the left ventricular and circulatory systems and their regulation by the central nervous system. On-line human parametric stimulation (parameter estimation) and consequential prognostic implications (based on parametric values) are demonstrated. Model responses to stimulated physiologic stresses help delineate tolerances of subjects. In order to have an estimate of the reliability of the model, the sensitivity of the model's responses to changes in the values of its intrinsic parameters is assessed. Also determined  is the extent to which errors in measuring the pressure affect the calculated values of the model's responses to changes in the values of its intrinsic parameters is assessed. Also determined is the extent to which errors in measuring the pressure affect the calculated values of the model's simulation parameters and subsequently influence the values of other diagnostically useful variables (such as contractility, oxygen consumption rate, heart rate), when the model is used to determine the limiting physiological stress sustainable by the subject. A comparison of the model's composition with those of other similar cardio-circulatory models is included.


Vascular dopamine receptors in the canine hindlimb. 1 Increases in femoral blood flow were produced by intra-arterial injections of dopamine (5-50 mug) in some but not all anaesthetized dogs studied, following treatment with the alpha-adrenoceptor antagonist, phentolamine. 2 The dilator effect of dopamine was not due to inhibition of adrenergic vasomotor tone as it was not affected by pharmacological procedures which completely abolished the activity of vastomotor nerves. 3 Blockade of vascular beta-adrenoceptors using propanolol reduced the flow increases produced by dopamine much less than it did those produced by isoprenaline. 4 Responses to dopamine were significantly depressed by intra-arterial administration of ergometrine (0.5 mg). This dose of ergometrine did not reduce femoral dilator responses to acetylcholine, histamine, isopienaline, bradykinin, or 5-hydroxytryptamine. 5 It is concluded that the femoral vascular bed in the dog contains specific vasodilator receptors for dopamine. Ergometrine appears to be a selective antagonist of dopamine at these receptors.


The effects of histamine and some histamine-like agonists on blood pressure in the cat. 1. The effects of histamine on blood pressure have been compared with the effects caused by four histamine-like agonists in anaesthetized cats. 2. It has been confirmed that the depressor responses to histamine involve both H1- and H2-receptors: depressor responses also follow the administration of selective H1- and H2-receptor agonists. 3. 2-Methylhistamine, in doses up to 1 X 10(-7) mol/kg, lowers blood pressure by interaction with H1-receptors. Larger doses of 2-methylhistamine also lower blood pressure but this may involve H2-receptors. 4. 4-Methylhistamine, in doses up to 1 X 10(-7) mol/kg, lowers blood pressure by interaction with H2-receptors. Larger doses of 4-methylhistamine also lower blood pressure but this may involve H1-receptors. 5. 2-(2-Aminoethyl)pyridine and 2-(2-aminoethyl)thiazole both lower blood pressure by interaction with H1-receptors only. 6. The potential value and limitations of these compounds as tools to investigate the cardiovascular effects of histamine are discussed.


Histamine receptors in peripheral vascular beds in the cat. 1. The vasodilator activity of histamine has been studied in anaesthetized cats. 2. Histamine causes dose-dependent vasodilatation in the vasculature of the hind-limb and mesentery, perfused with blood at constant flow. 3. Experiments using the selective antagonists mepyramine and metiamide indicate the involvement of both H1- and H2-receptors in the vasodilator responses to histamine. Mepyramine (2.5 X 10(-6) mol/kg), causes displacement of the histamine dose-response curve. This displacement is maximum with a dose-ratio of about 10. Further dose-dependent displacement of the dose-response curve occurred after metiamide (4 X 10(-7) mol kg-1 min-1 and 2 X 10(-6) mol kg-1 min-1), although these doses of metiamide had no effect on histamine responses in the absence of mepyramine. 4. Vasodilator responses could also be elicited by the selective H1-receptor agonists, 2-methylhistamine, 2-(2-aminoethyl)pyridine and 2-(2-aminoethyl)thiazole and the selective H2-receptor agonist, 4-methylhistamine. 5. The selectivity of mepyramine and metiamide as histamine receptor antagonists was confirmed by their failure to reduce the vasodilator responses to acetylcholine, isoprenaline and bradykinin.


Studies upon the mechanism by which acetylcholine releases surplus acetylcholine in a sympathetic ganglion. 1. Acetylcholine (ACh) releases surplus ACh from the superior cervical ganglion of the cat and the experiments described in this paper tested whether this results from exchange of endogenous ACh with exogenous ACh; the experiments also attempted to characterize pharmacologically the mechanism of this action of ACh. 2. The surplus ACh in the ganglion was radioactively labelled by perfusion of the ganglion with  [3H]-choline-Krebs solution containing diisopropylphosphofluoridate, and the release of surplus [3H]-ACh by [14C]-ACh injected close arterially to the ganglion measured. The amount of [3H]-ACh released by [14C]-ACh was 33 +/- 5 times greater than was the amount of [14C]-ACh accumulated by ganglia. The amount of exogenous ACh accumulated by ganglia that had first formed surplus ACh was not different from exogenous ACh accumulation by ganglia that had not formed surplus ACh. Thus, it is concluded that surplus ACh release by  ACh is not the result of ACh exchange. 3. In other experiments, surplus [3H]-ACh was accumulated in ganglia exposed to physostigmine. Nicotine, pilocarpine or ACh released surplus ACh; the effect of both nicotine and ACh was blocked by hexamethonium; atropine blocked the effect of ACh but not that of nicotine. It is concluded that both nicotinic and muscarinic receptors can be involved in the release of surplus ACh by cholinomimetic agonists.


Membrane potential changes induced by 5-hydroxytryptamine in the rabbit superior cervical ganglion. 1. Changes in resting membrane potential induced by 5-hydroxytryptamine (5-HT) have been measured in the excised ganglion by the sucrose-gap technique. 2. 5-HT produced a rapid depolarization, the threshold concentration for depolarization being around 10 muM. With concentrations of 100 muM or greater, repolarization began during the course of the superfusion; this was followed by prolonged tachyphylaxis. 3. Tachyphylaxis was largely avoided by making injections into the superfusion stream. Standard injections of 0.2 mumol 5-HT dissolved in 0.2 ml of Krebs solution were used routinely and could be given at 20-30 min intervals to evoke relatively constant responses. 4. The response to an injection consisted of a rapid depolarization, followed by a rapid repolarization and subsequent after-hyperpolarization. The threshold quantity for depolarization was around 0.01 mumol, while the ED50 estimated from 6 dose-response curves was 0.12 +/- 0.02 mumol (mean +/- s.e. mean). 5. Injections of 5-HT (0.2 mumol), choline (10 mumol) and acetylcholine (9.9 mumol) produced depolarizations of similar magnitude. 6. Monoamine oxidase inhibitors failed to alter substantially the amplitude of depolarizations to 5-HT. 7. 5-HT depolarizations were unaltered in amplitude when the impermeant anion benzenesulphonate was substituted for the chloride ion in Krebs solution, but were initially markedly reduced in amplitude in a sodium-deficient medium; some recovery of the response subsequently occurred. The depolarization which persisted in sodium-deficient solutions was much reduced or abolished when calcium ions were then removed from the superfusion medium. Removal of either calcium ions alone or potassium ions from the superfusion fluid did not reduce depolarization amplitude. 8. The after-hyperpolarization was abolished in sodium-deficient solutions, usually increased in potassium-free solutions, reduced or abolished by ouabain or nicotine, but unaffected by calcium free solutions. 9. A depolarizing action of 5-HT on presynaptic terminals in the ganglion appears probable.


Parallel bioassay of bombesin and litorin, a bombesin-like peptide from the skin of Litoria aurea. The spectrum of biological activity exhibited by litorin, a bombesin-like nonapeptide found in extracts of the skin of the Australian leptodactylid frog Litoria aurea was compared with that exhibited by the tetradecapeptide bombesin. 2 Litorin proved to be more potent than bombesin on isolated smooth muscle preparations and on the urinary bladder in situ. However, it was less potent on dog systemic blood pressure and kidney vasculature activation of the renen-angiotensin system being slight or lacking. 3 Gastrin release and acid secretion produced by litorin was more rapid in onset but less intense and less sustained than that elicited by bombesin. The same could be observed for pancreatic secretion. 4 Gall bladder contraction stimulated by litorin was probably caused by a double action of the peptide, directly on the bladder smooth muscle, and indirectly by cholecystokinin release. 5 In its effects on the myo-electric activity of the dog duodenum (inhibition of spikes and increase in frequency of pacesetter potentials leading to the appearance of a sequence of slow and small potentials) litorin possessed approximately 50 to 70% of the activity of bombesin.


Relative potency of bombesin-like peptides. The pharmacological activity of two natural bombesin-like peptides, alytesin and litorin, and 25 related synthetic peptides has been compared to that of bombesin. 2 The minimum length of the amino acid chain required for the first appearance of bombesin-like effects was represented by the C-terminal heptapeptide, and the minimum length for maximal effects by the C-terminal nonapeptide. The latter possessed approximately the same activity as bombesin and may be considered a good substitute. 3 Both the tryptophan and histidine residues seemed to be essential for bombesin-like activity. 4 The C-terminal octapeptide was less active than either bombesin or the C-terminal nonapeptide and its action was more rapid in onset and less sustained. 5 Litorin apparently has an intermediate position between bombesin octapeptide and bombesin nonapeptide in the speed and duration of its effects. The relationship between structure and activity is discussed.


Effects of oestradiol and progesterone on the in vitro production of prostaglandin F2alpha by the guinea-pig uterus. 1 The effects of oestradiol and progesterone on the production of F  2alpha by the guinea-pig uterus in vitro have been studied. 2 Ovariectomized guinea-pigs were treated with oestradiol benzoate, progesterone, or a combination of these hormones. The uteri were homogenized and incubated and the prostaglandin F2alpha produced was measured by radiommunoassay or combined gas chromatography-mass spectrometry (g.c.-m.s.). Oestradiol treatment or progesterone followed by oestradiol caused a significant increase in prostaglandin F2alpha synthesis compared with control values, whereas progesterone treatment caused no significant increase. 3 The uteri from guinea-pigs on day 7 of the oestrous cycle were split into four parts, and each part homogenized and incubated either alone or in the presence of oestradiol-17beta, progesterone, or a combination of these hormones. Prostaglandin F2alpha was measured by g.c.-m.s. Oestradiol was found to increase prostaglandin F2alpha synthesis by the uterus whereas progesterone had no effect. However, progesterone did inhibit the response to oestradiol. 4 Oestradiol treatment of the guinea-pig uterus causes an increase in capacity to produce prostaglandin F2alpha in vitro. The role of progesterone is difficult to interpret.


Rapid reduction of prostaglandin 15-hydroxy dehydrogenase activity in rat tissues after treatment with protein synthesis inhibitors. 1 The capacity of rat kidneys to metabolize prostaglandins is rapidly lost when de novo protein synthesis is reduced by cycloheximide and puromycin. Enzyme activity declines to about half control values 45-75 min after a single dose of cycloheximide. Prostaglandin metabolism by the lung is also diminished. 2 These inhibitors apparently act by preventing the synthesis of new prostaglandin 15-hydroxy dehydrogenase enzyme. 3 The RNA synthesis actinomycin D has no effect on metabolism. 4 It is concluded that prostaglandin dehydrogenase is a short-lived enzyme in the cell whose replacement depends upon de novo protein (but not RNA) synthesis. The implications of this finding are discussed.


Reacting to autistic children: the danger of trying too hard. Recent work has revealed that autistic children's predominating tendency to avoid social interactions is actually enhanced by the 'friendly' approaches to others. In this study it was recorded on video-tape how eight autistic children reacted to four styles of adult behaviour. The adult reacted to the child's looks at her by (i) smiling, (ii) gaze averting, (iii) gaze averting plus other 'timid' behaviours and (iv) doing nothing except continuing to look back. For this last condition--when the adult did not react--it was found that autistic children showed less avoidance behaviour after eye contact and spent more time within one metre of the adult. The implications for treatment are contrary to much modern practice and to what seems to be adults' 'natural' response. Reactivity by others appears to enhance the child's avoidance, and it is suggested that adults should be circumspect in the degree of sociability with which they respond to autistic children.


Subcultural mental handicap.

Subcultural mental handicap. Some conceptual problems in relation to the interaction of genetic influence and social disadvantagement are discussed, and some of the results of a study of 144 families with mentally handicapped children reported. The work of Heber and his associates in Milwaukee is briefly reviewed, and the Edinburgh data discussed in relation to the study in Aberdeen by Birch et al. (1970). Possible strategies for intervention are considered.


Use of a standardized psychiatric interview in mentally handicapped patients. This study attempted to assess the applicability of the Clinical Interview Schedule (Goldberg et al., 1970) to mentally handicapped patients in a hospital. Twenty-seven patients were rated simultaneously by three raters. Of the 31 items assessed for reliability, 11 were completely satisfactory, 8 were satisfactory, 6 unsatisfactory and 6 'not proven'. Ratings made by all raters for overall severity of psychiatric illness correlated significantly with similar ratings made by the consultants responsible for the patients.


Drug therapy in mental handicap.

Drug therapy in mental handicap. Definitions of mental handicap are imprecise in practice, and a wide spectrum of patients are provided for under this heading. There can be no question of specific treatment for 'mental handicap' as such. Many situations arising in institutions for the mentally handicapped derive from the nature of the institution and the regime. Drugs may be used 'faute de mieux' when environmental manipulation would be more appropriate. There is much over-prescribing, and the choice of drugs is not always logical; monitoring of dose is seldom employed. A major source of behaviour disturbance in the mentally handicapped is lack of suitable occupation. Apart from a few specific indications, use of sedatives and tranquillizers for the mentally handicapped should be seen as a holding device, to enable a different system of management to be adopted or to disrupt an undesirable behaviour pattern.


The frequency of visual hallucinations in schizophrenic patients in Saudi Arabia. Sixty-nine schizophrenic patients (52 men and 17 women) who were consecutive admissions to Shehar Psychiatric Hospital, Taif, Saudi Arabia, were investigated for the phenomenology and frequency of visual hallucinations. Of these patients 43 (62 per cent) were visually hallucinated. It is concluded that visual hallucinations in schizophrenia are of common occurrence in this country. The need for further investigation as to the part played by cultural and other factors is emphasized.


Psychiatric diagnosis in New South Wales compared to England and Wales. Comparative studies of first admission rates to psychiatric hospitals have revealed significant differences in the rates of diagnoses of functional psychoses between the United Kingdom and the United States of America. The present study examined the diagnoses of indigenous patients born between 1921 and 1955 and first admitted to hospitals in New South Wales, Australia, and England and Wales. Admission rates for mania were in striking agreement. The rate in New South Wales for schizophrenia was slightly higher and for psychotic depression considerably less than in England and Wales. A similar trend in diagnostic dissonance would appear to exist between England and Wales and New South Wales as between England and Wales and the United States for schizophrenia and psychotic depression, but this is considerably less in degree.


A factor-analytical study of depression across cultures (African and European). In a factor-analytical study of depression across two cultures, African and European, certain similarities and important differences were found. Depression in African cultures presented principally as depressed mood, somatic symptoms and motor retardation. In European cultures depression presented with depressed mood, guilt, suicidal ideas, motor retardation or anxiety. Both groups lost interest in work and the environment. Guilt and suicidal ideas and acts are uncommon in African sample, and appear to be culturally determined.


Deliberate self-harm: clinical and socio-economic characteristics of 368 patients. In this study 368 patients were interviewed after they had attended the Bristol Royal Infirmary Accident and Emergency Department following a non-fatal act of deliberate self-harm. There were twice as many women (247) as men (121), and two thirds of the patients were in the 15-35 age group. Ninety-five per cent had taken a drug overdose, most commonly one or more of the tranquillizers, antidepressants, hypnotics or analgesics. Seventy-eight per cent had taken drugs prescribed by a doctor. Half the patients mentioned interpersonal conflict as a major precipitating factor in the episode. A psychiatric diagnosis was completed for all admitted patients, of whom 52 per cent were considered to be suffering from neurotic depression, 29 per cent from personality disorder, 12 per cent from functional psychosis and 10 per cent from alcohol addiction. Almost half had deliberately harmed themselves on a previous occasion. The series showed a greater than average incidence of unemployment, overcrowded living conditions, divorce and antisocial behaviour. The implications of these findings for the clinical management and prevention of non-fatal deliberate self-harm are discussed.


A further investigation of differences in the suicide rates of England and Wales and of Scotland. National samples of case records of suicidal-type deaths from England and Wales and from Scotland were reassessed by officials in the other country. It emerged that similar criteria for suicide existed in both countries, and that there was no age-related tendency to misclassify cases. The lower official suicide rate amongst the old in Scotland was therefore considered not to result from ascertainment differences. It was also concluded that Scottish records were not so briefly documented as to prevent the conclusive ascertainment of cause by England and Wales coroners. Cases which were designated 'undetermined' in Scotland tended to be classified 'accidental' by coroners. Reasons for the lower incidence of suicide in Scotland are discussed.


Sterilization: a review of 98 sterilized women. The details of 98 women sterilized over a three-year period are presented. They show that female sterilization is a safe procedure which has a satisfactory result in many cases and confers many secondary benefits. However, some regret is common and is associated with a high incidence of psychiatric and marital morbidity, and this is shown to be related to pre-operative factors. A method of pre-operative assessment is outlined which should minimize the risk of a poor outcome following female sterilization.


Psychological aspects of isolator therapy in acute leukaemia. Treatment under conditions of gnotobiotic isolation can augment the stress of adaptation to a diagnosis of leukaemia. Identification of the psychological problems experienced in isolator treatment can contribute to the effective maintenance of therapy. Individual patterns of adjustment to treatment relate to the psychological defence mechanisms employed to contend with the dependent position enforced by isolation. Psychiatric assessment can assist both patients and nursing staff with the management of their separate difficulties in this unfamiliar treatment situation. Psychological features of isolator treatment in ten patients with acute leukemia are described and suggestions proposed for psychological management of patients under isolator conditions.


Effect of ADP on PGE1 formation in blood platelets from patients with depression, mania and schizophrenia. Adenosine diphosphate (ADP) stimulates the synthesis of prostaglandin E1 (PGE1) in lysed platelets from normal subjects, patients with affective illness but not in platelets from cases of schizophrenia. The stimulation is concentration-dependent and follows a curve which is mildly sigmoid in the normal, markedly sigmoid in depression and hyperbolic in mania.


The relationship of plasma to erythrocyte lithium levels in patients taking lithium carbonate. Plasma and erythrocyte lithium levels have been determined repeatedly in twelve patients taking lithium carbonate for affective disorders. In any individual the plot of the plasma lithium level against erythrocyte/plasma ratio is linear, but the ratio can either increase or decrease with increasing plasma lithium concentration. Erythrocyte/plasma ratio is an unsound basis for comparing individual responses to lithium.


Intravenous tranquillization with ECT.

Intravenous tranquillization with ECT. Forty depressed in-patients for whom electro-convulsive therapy had been prescribed were rated before treatment on depression and anxiety scales. Side effects, post-operative agitation and retrograde memory impairment were assessed in each patient after each of several treatments. Results were compared when no tranquillizer was given and when either diazepam or haloperidol was administered intravenously immediately before the anaesthetic. It was found than when ECT was given without tranquillization, the incidence and severity of post-operative agitation and of side effects were significantly greater in those patients with a high level of anxiety before treatment. Both diazepam and haloperidol were found to be effective in subduing agitation and side effects in anxious, depressed patients, but with diazepam recovery time was longer.


Subjective side-effects of ECT.

Subjective side-effects of ECT. The incidence of side-effects present 24 hours after electroconvulsive therapy was studied in 96 patients who between them received 500 treatments in a consecutive series. None of the side-effects occurred frequently: headache was experienced after 2-6 per cent and subjective memory impairment after 3 per cent of treatments. None of the unwanted effects held any serious physical threat. The aspect of ECT most disliked by the patients in this study, and mentioned by 16 per cent of them, was the fear of permanent memory upset.


Cervical cytology in genital infection.

Cervical cytology in genital infection. Papanicolaou-stained cervical smears taken from 203 female patients with either gonorrhoea, trichomoniasis, or candidosis were examined for the degree of inflammatory change. The results from these patients were compared with the results of smears taken from women who had no evidence of sexually-acquired infection after full assessment in the clinic. Gonorrhoea and trichomoniasis were associated with inflammatory changes but these were less marked in patients with candidosis. It is concluded that, before cytological inflammatory changes are attributed to non-specific genital infection, it is important to exclude gonorrhoea, trichomoniasis, and, to a lesser extent, candidosis.


Reiter's disease in a female, presenting as erythema nodosum. The case history of a female who presented with erythema nodosum is described, and the diagnosis of Reiter's disease is proposed. Reference is made to literature on Reiter's disease in the female and to sacroiliac joint abnormalities which have been observed in this condition.


Tabes dorsalis with sudden onset of paraplegia. A case is presented of tabes dorsalis with spinal gumma producing collapse of the L5 vertebra followed by paraplegia.