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Different factors possibly involved in post-translational regulation of ornithine decarboxylase activity.

Present results concern a microsome-bound enzymatic system which has been recognized as responsible for the rapid inactivation in vitro of ornithine decarboxylase (ODC). Two different models have been investigated: a) rat liver after a single thioacetamide administration, and b) the 3924 A Morris hepatoma. In both these models we observed variations in the microsome-bound ODC-inactivating capacity. In parallel, changes in ODC properties were observed. The possibility of a causal relationship between the two events is discussed. The actual role of the microsome-bound ODC-inactivating system, in ODC activity regulation in vivo cannot be established, but it remains as a fairly plausible working hypothesis.

Animals↗

THE CHILLIWACK RESPIRATORY SURVEY, 1963: 3. THE PREVALENCE OF RESPIRATORY DISEASE IN A RURAL CANADIAN TOWN.

The prevalence of chronic respiratory symptoms and of abnormalities in pulmonary function was determined by a survey of persons, aged 25 to 74, residing during May and June 1963 in a rural town, Chilliwack, B.C. Morning phlegm was reported by 26% of men and 13% of women. Chronic bronchitis was considered present in 21.5% of men and 11.3% of women. More serious obstructive lung disease, not related to heart disease, was found in 12.6% of men and 8.7% of women. These prevalences were higher than those found by the authors at Berlin, New Hampshire, U.S.A., in 1961. Demographic factors, such as birthplace, occupational class and measures of social stability, were not related to the prevalence of respiratory disease at Chilliwack. Some observer variation was found after analysis to be the result of non-randomization of respondents among the observers. An incidental observation was a high prevalence at Chilliwack of heart disease and hypertension under treatment.

Asthma↗

[Behavior of plasma and urine purines, after a purine-free diet, in normal subjects and patients with gout].

Plasma and urine oxypurines (hypoxanthine and xanthine) and uric acid, were evaluated in normal subjects and in gouty patients before and after a purine free diet. After a 7-days period, plasma oxypurines were remarkably higher in normal subjects, while they did not undergo variations in gouty patients, which showed higher in basal conditions. No significant changes in urinary excretion were observed in both cases. The interpretation of the observed variations is discussed.

Adult↗

A preliminary pharmacokinetic study of cyclosporine A in 10 Japanese renal transplant patients.

A pharmacokinetic study of cyclosporine A (CyA) was performed in ten Japanese renal transplant patients. The peak blood CyA concentration appeared at about 2.5 h after oral administration of CyA 180-360 mg, and the mean peak CyA concentration was 582 +/- 238 (SD) ng/ml. The apparent clearance was 39.9 +/- 16.9 (SD) ml/min/kg which is almost the same as reported in European transplant patients. The apparent distribution volume was 5.34 +/- 3.05 (SD) l/kg. The wide variations observed both in the apparent clearance and in the apparent distribution volume are ascribed to the wide variation of the area under the curve (AUC). No correlation was found between the oral dose per body weight and peak blood CyA level or AUC in the 10 subjects. However, a linearity was ascertained between blood CyA concentrations and oral CyA doses (250 mg and 500 mg), though in one patient. Especially, in one patient, blood CyA level was under the lower detection limit of our assay method, 50 ng/ml, over 20 h after oral administration of CyA. This study strongly supports the need of the blood monitoring in the CyA therapy after renal transplantation.

Adult↗

Insulin radioimmunoassay measurement by the polyethyleneglycol separation technique using the ROTOP kit reagents. Some clinical applications.

The technique described in the instructions booklet of the radioimmunoassay Insulin kit commercially known as the ROTOP-Insulin kit (CCR) tested both in our and in other laboratories did not show the desired reproducibility. Using the main ROTOP reagents (anti-insulin serum and 125I-Insulin) in radioimmunoassay (RIA) systems with other separation techniques (double antibody, dextran-charcoal and polyethyleneglycol) we observed that these reagents are suitable for a sensitive and precise RIA system. The intra-assay variations observed were caused by the separation technique with 86% ethanol as proposed by the procedure. This work describes an insulin-RIA system modified in order to be able to use the ROTOP reagents with the polyethyleneglycol (PEG) separation technique. This variant is used for more than three years in our laboratory but was adopted also in other RIA laboratories in Romania.

Charcoal↗

Met and unmet demand for hospital beds. Some recent evidence.

Many commentators have noted the interrelation of demand and supply of hospital beds and have suggested that an increase in the supply of hospital beds tends to generate additional demand either in the form of more patients admitted or patients treated for longer periods of time or some combination of the two. We can report that the bed use rate can be predicted more accurately in terms of the five-seventh rule, that is if a National Health Service bed is made available for an additional week, then for five out of seven days it will be occupied. This rule was found to apply at both regional and district level. Variation in admission rates was also investigated and it was found that a large proportion of the observed variation could be explained in terms of one variable--bed supply. In view of the Resource Allocation Working Party's proposals, the relationship between the overall standardized mortality ratio and bed supply, admissions rate and bed use rate was investigated. No significant effect, however, was discovered. In other words, it is bed supply which strongly influences the demand for hospital care and not the overall standardized mortality ratio.

Bed Occupancy↗

Reproducibility of DNA measurements in imprints of thyroid adenoma. Variation sources.

DNA measurement represents a type of quantitative analysis which allows us to gain prognostic information on malignant tumors and to study the natural history of the epithelial neoplasia. However, there are sources of variation in evaluating the DNA content. These include variation due to field selection, variation between observers (interobserver variation), and variation between laboratories (interlaboratory variation). The influence of various variation sources was studied in 4 experiments. When DNA measurements were made from the same microscopic fields, the results did not differ remarkably. However, observer training proved to be important. Intra- and interobserver variation was lower among experienced morphometrists than among inexpert observers. Different laboratories and image analyzers may give different results when the same case is measured. To overcome at least part of the potential variation sources, undergraduates and postgraduates at the Departments of Pathology of Ancona and Kuopio Universities are specially trained in the use and application of morphometry. Special sampling rules should be applied and observers encouraged to follow the rules as uniformly as possible.

Adenoma↗

Morphometric evaluation of dark and clear epidermal basal cells during early 2-stage chemical skin carcinogenesis in the hairless mouse using two different fixation methods.

Ultrastructural morphometric characteristics of basal keratinocytes in hairless mouse epidermis were analyzed statistically. The following variables were assessed: (i) low versus physiological osmolality during fixation, (ii) alterations induced by a 2-stage carcinogenesis regimen using DMBA and TPA, (iii) criteria for a cell being dark versus being clear, (iv) inter-observer variation. The results show that with low fixation osmolality most basal cells swell and become electron lucent. The few cells which apparently do not swell stand out as shrunken electron dense dark cells. Morphometrically they are more differentiated than clear cells, but do share many features with the basal cell type which appears after fixation in a buffer of physiological osmolality. Iso-osmolality during fixation seems to induce a homogeneous basal cell population of relatively electron dense cells without typical dark and clear elements. Treatment with DMBA/TPA induces not only intercellular edema and reduced desmosomal contacts, but causes injury to the plasma membrane leading to hydropic changes in the cells. This general intra- and intercellular DMBA/TPA induced hydration might induce secondary compression of some of the cells, leading to an increased number of compressed dark cells. It is, however, only after fixation in low buffer osmolality that these effects of DMBA/TPA are statistically significant and clearly observable. The inter-person variation was, apart from a few instances, either not statistically significant or did not interfere with the other effects. We did not find clear arguments in favor of the view that dark cells are primitive epidermal stem cells. They seem only to reflect non-specific toxic effects of tumor promoters, which appear only under certain fixation conditions, that have been used by most authors. The results suggest that dark and clear cells are mainly a consequence of the degree of cellular hydration.

9,10-Dimethyl-1,2-benzanthracene↗

Proteome analysis of Neisseria meningitidis serogroup A.

Neisseria meningitidis is an encapsulated Gram-negative bacterium responsible for significant morbidity and mortality worldwide. Meningococci are opportunistic pathogens, carried in the nasopharynx of approximately 10% of asymptomatic adults. Occasionally they enter the bloodstream to cause septicaemia and meningitis. Meningococci are classified into serogroups on the basis of polysaccharide capsule diversity, and serogroup A strains have caused major epidemics mainly in the developing world. Here we describe a two-dimensional gel electrophoresis protein map of the serogroup A strain Z4970, a clinical isolate classified as ancestral to several pandemic waves. To our knowledge this is the first systematically annotated proteomic map for N. meningitidis. Total protein samples from bacteria grown on GC-agar were electrophoretically separated and protein species were identified by matrix-assisted laser desorption/ionization time of flight spectrometry. We identified the products of 273 genes, covering several functional classes, including 94 proteins so far considered as hypothetical. We also describe several protein species encoded by genes reported by DNA microarray studies as being regulated in physiological conditions which are relevant to natural meningococcal pathogenicity. Since menA differs from other serogroups by having a fairly stable clonal population structure (i.e. with a low degree of variability), we envisaged comparative mapping as a useful tool for microevolution studies, in conjunction with established genotyping methods. As a proof of principle, we performed a comparative analysis on the B subunit of the meningococcal transferrin receptor, a vaccine candidate encoded by the tbpB gene, and a known marker of population diversity in meningococci. The results show that TbpB spot pattern variation observed in the maps of nine clinical isolates from diverse epidemic spreads, fits previous analyses based on allelic variations of the tbpB gene.

Agar↗

Substitution rate variation among sites in hypervariable region 1 of human mitochondrial DNA.

More than an order of magnitude difference in substitution rate exists among sites within hypervariable region 1 of the control region of human mitochondrial DNA. A two-rate Poisson mixture and a negative binomial distribution are used to describe the distribution of the inferred number of changes per nucleotide site in this region. When three data sets are pooled, however, the two-rate model cannot explain the data. The negative binomial distribution always fits, suggesting that substitution rates are approximately gamma distributed among sites. Simulations presented here provide support for the use of a biased, yet commonly employed, method of examining rate variation. The use of parsimony in the method to infer the number of changes at each site introduces systematic errors into the analysis. These errors preclude an unbiased quantification of variation in substitution rate but make the method conservative overall. The method can be used to distinguish sites with highly elevated rates, and 29 such sites are identified in hypervariable region 1. Variation does not appear to be clustered within this region. Simulations show that biases in rates of substitution among nucleotides and non-uniform base composition can mimic the effects of variation in rate among sites. However, these factors contribute little to the levels of rate variation observed in hypervariable region 1.

Biological Evolution↗

Relaxation of isolated human pulmonary muscle preparations with prostacyclin (PGI2) and its analogs.

The effects of PGI2 and two analogs Iloprost and ZK 96480 were examined on isolated human pulmonary muscle preparations. High concentrations of these agents reduced the basal tone in all types of preparations. In addition, they relaxed tissues which had been maximally contracted with histamine (50 microM). PGI2 was more potent on pulmonary arterial muscle preparations (pD2 value: 6.33, n = 3) than on bronchial muscles. The relaxations induced by PGI2 in bronchial preparations were quite variable, that is, some tissues relaxed while others did not. The analogs also relaxed arterial preparations and the pD2 values were approximately the same (Iloprost: 7.42, n = 4 and ZK 96480: 7.48, n = 4). The isolated human pulmonary vascular preparations were approximately 10-fold more sensitive to the analogs than bronchial muscle preparations. In bronchial tissues we noted that the PGI2 relaxant effect was spontaneously reversed with time, an activity not observed with both analogs. A pretreatment of the bronchial tissues with indomethacin (1.7 microM) did not reduce the variations observed with PGI2 nor modify the transient relaxation observed with this agent. These data demonstrate that vascular tissues from the human lung are considerably more sensitive to these relaxant agonists than bronchial preparations.

Bronchi↗

Binding of human TNF-alpha to high-affinity cell surface receptors: effect of IFN.

Human tumor-necrosis factor (INF-alpha), induced by Sendai virus in peripheral blood mononuclear leukocytes (PBMC), was isolated using a monoclonal antibody to the protein and radioiodinated by the chloramine-T method. Effective labelling of the protein with little loss of bioactivity was obtained. The labelled protein was found to bind specifically to high affinity receptors present on cells of various cultured lines. The molecular nature of these receptors was examined using the bifunctional cross-linking reagents disuccinimidyl suberate (DSS) and dithiobis succinimidyl propionate (DSP). In SDS-PAGE, conjugates between TNF receptors and the labelled TNF of two sizes (about 75 and 92 kDa) were detected. 125I-labelled TNF was also used to examine variations in TNF receptor concentration, upon treatment of cells by interferon (IFN) or TNF, and any correlation of observed variations with the effect of IFN and TNF on responsiveness of cells to the cytotoxicity of TNF. The decreased vulnerability of cells to the cytotoxic effect of TNF, following treatment of cells by TNF itself, was not correlated with decreased availability of free receptors for the protein. However, an increase in responsiveness of cells to TNF following treatment by IFN was accompanied by some increase in binding of TNF to the receptors.

Cell Line↗

Southern Ocean sea-ice extent, productivity and iron flux over the past eight glacial cycles.

Sea ice and dust flux increased greatly in the Southern Ocean during the last glacial period. Palaeorecords provide contradictory evidence about marine productivity in this region, but beyond one glacial cycle, data were sparse. Here we present continuous chemical proxy data spanning the last eight glacial cycles (740,000 years) from the Dome C Antarctic ice core. These data constrain winter sea-ice extent in the Indian Ocean, Southern Ocean biogenic productivity and Patagonian climatic conditions. We found that maximum sea-ice extent is closely tied to Antarctic temperature on multi-millennial timescales, but less so on shorter timescales. Biological dimethylsulphide emissions south of the polar front seem to have changed little with climate, suggesting that sulphur compounds were not active in climate regulation. We observe large glacial-interglacial contrasts in iron deposition, which we infer reflects strongly changing Patagonian conditions. During glacial terminations, changes in Patagonia apparently preceded sea-ice reduction, indicating that multiple mechanisms may be responsible for different phases of CO2 increase during glacial terminations. We observe no changes in internal climatic feedbacks that could have caused the change in amplitude of Antarctic temperature variations observed 440,000 years ago.

Calcium↗

Lipoprotein predictors of the severity of coronary artery disease in men and women.

In this study we examined the relationships between levels of several components of plasma lipoproteins and severity of coronary artery disease in 65 men and 42 women who underwent coronary arteriography for suspected coronary disease. Severity of coronary atherosclerosis was scored as the extent of disease seen at arteriography. Univariate analyses of the relationships between the plasma lipoprotein parameters and score for severity of atherosclerosis revealed a marked difference between men and women. In men, the score for severity of atherosclerosis was strongly related to the low-density lipoprotein (LDL) cholesterol and apolipoprotein B concentrations, whereas in women it was related to the triglyceride concentrations in plasma intermediate-density lipoprotein (IDL) and LDL and to the cholesterol and apolipoprotein B concentrations in IDL. The significance of these correlations was not negated by possible confounding factors such as alcohol intake, diabetes, and treatment with thiazides and beta-adrenergic blockers. Stepwise regression analyses of data adjusted for weight and age indicated that 22% of the variation in the score for severity of atherosclerosis could be accounted for by levels of LDL cholesterol in men. No other lipoprotein parameter could account for any further variation. In contrast, cholesterol did not account for any variation in the score for severity of atherosclerosis in women, whereas plasma triglyceride accounted for 16% of the observed variation in this group. No relationships were found between score for severity of atherosclerosis and high-density lipoprotein cholesterol or plasma apolipoprotein A-I concentrations in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Survivability of Shigella dysenteriae type 1 & S. flexneri 2a in laboratory conditions simulating aquatic environment.

BACKGROUND & OBJECTIVES: Information about the duration of survival of Shigellae in water is speculative. The present study was undertaken to assess the duration of survival of Shigella dysenteriae type 1 and S. flexneri type 2a in the laboratory conditions simulating the aquatic environment, their invasive property and the association of different physico-chemical parameters in the survival process. METHODS: Five natural water sources were selected in a diarrhoea prone rural area. Collection of water, determination of physico-chemical parameters and bacteriology were carried out following standard procedures. Filter-sterilised water samples were inoculated with S. dysenteriae type 1 and S. flexneri 2a and survival was monitored by estimating total viable count at regular intervals. Bivariate correlations between the duration of survival and physico-chemical parameters were estimated. Multiple linear regression models were fitted for the duration of survival of the bacteria. RESULTS: All water sources were contaminated with faecal coliforms including Escherichia coli, S. dysenteriae type 1 survived for a mean duration of 3.33 days and S. flexneri 2a for mean 11.167 days in field water samples in laboratory condition. Duration of survival had positive correlation with the initial bacterial counts. In the multiple regression model the strongest predictor of the duration of survival of both S. dysenteriae type 1 and S. flexneri 2a was the concentration of bacteria. Other possible predictors for S. flexneri 2a were Mg and water temperature. INTERPRETATION & CONCLUSION: S. dysenteriae type 1 with epidemic potential survives for shorter duration than S. flexneri 2a. Although some of the physico-chemical parameters had positive relation with duration of survival, the variation of these in natural water samples studied has not caused much variation in the survival in case of S. dysenteriae type 1. In case of S. flexneri 2a, the observed variation in Mg concentration can cause up to 25 days difference in the duration of survival and thus could be a factor determining the endemicity of S. flexneri 2a infection.

Shigella dysenteriae↗

[Seasonal variation of mortality from cerebro-cardiovascular diseases--effect of ambient temperature on death].

A study to clarify the relationship between seasonal variations in mortality from cerebro-cardiovascular diseases and ambient temperature (maximum/minimum temperature and daily range) was performed using time series analysis, and the role of ambient temperature as an associated factor in cerebro-cardiovascular disease caused death was discussed. The following results were obtained: 1) The seasonality factor associated with the monthly variation for mortality was of greater magnitude for heart diseases more than for cerebral diseases. There was a tendency for mortality from cardiac diseases to decline gradually from February/March to July/August, and to increase in October/November, with a maximum peak in the curve of seasonal variation observed in January/February. 2) The seasonal factor associated with maximum/minimum temperature and daily temperature range showed a stable variation in magnitude from January to December, with temperatures displaying a single peak in August. Daily temperature range was lowest during summer and highest during the late fall, winter or early spring. 3) A statistically significant negative correlation was seen between mortality from cerebro-cardiovascular diseases and seasonality and temperature, while a positive correlation was seen between mortality and daily temperature range, suggesting that low environmental temperatures may operate indirectly as a factor that affects cerebro-cardiovascular disease mortality.

Cerebrovascular Disorders↗

Seasonal variations of serum lipids and apoproteins.

Seasonal variations of blood lipids, which must be considered when performing long-term studies, could be partially due to dietary changes. In the present study, serum lipid parameters were measured each month for 1 year in nuns living in a monastery, whose diet was perfectly regular and controlled. The serum lipid variations observed consisted mainly of an increase in total cholesterol, low-density lipoproteins and apolipoprotein B in autumn and spring and an increase in high-density lipoprotein cholesterol in winter, whereas apolipoproteins A-I and A-II showed a marked increase in summer and at the beginning of autumn. These variations were probably induced by factors directly related to seasonal rhythm and not to dietary factors or physical exercise. Lastly, the influence of sex hormones seems to be very minor, as postmenopausal women (one-third of the persons) had an identical variation in their lipid parameters, to that observed in the whole group.

Adult↗

Rb-Cs ratio as an indicator of fish diet in lakes of the Patagonia, Argentina.

The ratios of Rb to Cs contents were studied in five fish species from seven lakes located in the Patagonia Andean Range, Argentina in order to trace fish diet. The species studied were native velvet catfish (Diplomistes viedmensis) and creole perch (Percichthys trucha), and exotic brown trout (Salmo trutta), rainbow trout (Oncorhynchus mykiss), and brook trout (Salvenilus fontinalis). Rainbow trout specimens from two farms were also studied, as well as fish food items and native mussels (Diplodon chilensis). Rb and Cs concentrations were determined by instrumental neutron activation analysis. A positive correlation of Cs concentration in the muscle of velvet catfish with fish length was observed, probably associated with the long biological half-life of this element in this species, whereas the Rb concentration remained constant, hence inhibiting the use of Rb-Cs ratios as a tracer in this case. Seasonal variations observed for rainbow trout and Cs concentration background bias in one of the lakes studied are also a limiting factor to the use of Rb-Cs ratios as a diet tracer. Rb-Cs ratios allowed clear differentiation of rainbow trout raised in farms from the natural specimens that lived in the same environment, in agreement with Rb-Cs ratios determined in both diets. Rb-Cs ratios in rainbow trout showed significant differences between Rivadavia and Futalaufquen lakes compared to Moreno and Nahuel Huapi lakes, which could be associated with a higher participation of plankton in the diet in the first case. No relevant variations in Rb-Cs ratios of brown trout were observed, probably because of the similarity in the diet.

Animals↗