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Biomedical subjects

S Wade

Publications and source records attributed to S Wade.

At least 55 records · Page 3Linked to original sources
PubMed1988

Genetic control of murine T cell proliferative responses to Mycobacterium leprae. V. Evidence for cross-reactivity between host antigens and Mycobacterium leprae.

T cell proliferative responses to Mycobacterium leprae were measured by immunization of mice at the base of the tail with Ag and challenging lymphocytes from draining lymph nodes in culture with M. leprae. C57BL/10J and B10.BR mice were identified as low responder mice and the congenic strains B10.M, B10.Q, and B10.AKM as high responders whereas F1 (high x low) hybrid mice were found to be low responders. The cellular basis of low responsiveness did not appear to result from a defect in Ag-presenting cells or the activation of suppressor T cells by M. leprae. The influence of the environment in which T cells developed on responsiveness to M. leprae was analyzed in chimeric mice prepared by irradiating F1(C57BL/10J x B10.M) mice and reconstituting with bone marrow from C57BL/10J, B10.M, or F1 donors. Six weeks later, chimeric mice were immunized with M. leprae, lymph node cells were subsequently prepared, and H-2 phenotyped and challenged in culture with M. leprae Ag. T cell proliferative responses were found to be low in all cases, similar to those observed using lymph node cells from F1 hybrid mice. These results suggested that high responder B10.M lymphocytes developing in the irradiated F1 mice became tolerized to antigenic determinants found on M. leprae. This implied cross-reactive epitopes existed between some mouse strains and M. leprae. Low responsiveness to M. leprae in low responder and F1 hybrid mice may result from tolerance to H-2-encoded Ag that show cross-reactivity with M. leprae.

Animals↗
PubMed1988

Thymulin (Zn-FTS) activity in protein-energy malnutrition: new evidence for interaction between malnutrition and infection on thymic function.

The combined effects of protein-energy malnutrition (PEM) and infection on thymic function evaluated by specific plasma thymulin activity were studied in Senegalese children: 29 hospitalized in Dakar for severe malnutrition and various diseases; 9 infected without sign of severe PEM, living in Dakar; 13 apparently healthy, uninfected, living in Dakar; and 7 apparently healthy, uninfected, living in Paris. Most of the free-living children in Dakar suffered from mild to moderate PEM. The specific thymulin activity (total plasma activity minus the activity recorded after adsorption of the plasma with a monoclonal antithymulin antibody) was almost undetectable in the infected children and was normal only in the children living in Paris. Such activity might be decreased by moderate and severe PEM and severe malnutrition may not be the only underlying cause of depressed level of thymulin in malnourished children from the Third World. Concurrent infections are important factors.

Blood Proteins↗
PubMed1988

Rat transthyretin: effects of acute short-term food deprivation and refeeding on serum and cerebrospinal fluid concentration and on hepatic mRNA level.

To gain some insight into the nutritional factors that affect the blood level of transthyretin (TTR) and its metabolism, we have investigated the response of rat TTR to 1, 2 and 3 d of fasting and to 24 h of fasting followed by refeeding. The observed changes were compared to the level of TTR in cerebrospinal fluid (CSF) and to the amount of circulating thyroid hormones. Dot hybridization of a hepatic mRNA-cDNA probe specific for TTR was used to measure the relative level of TTR mRNA. Serum TTR decreased significantly after fasting and the decrease was proportional to the duration of the treatment. When rats were fasted for 24 h and then refed, serum TTR levels remained low after 2 d of refeeding. The dot hybridization results suggested that reduced liver synthesis was not the only mechanism that could explain this long-lasting effect of fasting. The TTR level in CSF was not influenced by fasting. In addition to the high sensitivity of serum TTR to food deprivation, the study also showed two distinct influences of fasting on the thyroid hormones: a primary effect that probably results in an inhibition of the conversion of thyroxine (T4) to triiodothyronine (T3) and a decreased T4-bound fraction, probably as a result of decreased serum level of TTR.

Animals↗
PubMed1988

Value of serum transthyretin measurements in the assessment of marginal protein-energy malnutrition in rats.

The influence of a wide range of protein and/or energy intakes on the serum level of rat transthyretin was studied. Young and adult rats were fed ad libitum diets containing 18, 9, 6, 4 and 0.5% protein (wt/wt) or were fed a control diet in restricted amounts. The transthyretin level was lower in young rats and was normal or slightly higher in adult rats fed low protein diets than in those fed the 18% protein diet. It was decreased with decreasing energy intake in all energy-restricted rats. Moderate energy restriction in rats fed equivalent amounts of protein also lowered the transthyretin level. Rats with similar body weights and similar protein intakes showed marked differences in serum transthyretin level, depending on the amount of energy consumed. Serum transthyretin changes were discussed in relation to the level of transthyretin in cerebrospinal fluid and to the serum concentration of albumin, transferrin and thyroid hormones. The results show that serum transthyretin is more closely related to the protein and energy intakes than to the protein and energy content of the diet. Our results indicate that serum transthyretin measurement is a reliable marker in the detection of early moderate and severe protein-energy restriction.

Animals↗
PubMed1987

Macrophage function as studied by the clearance of 125I-labeled polyvinylpyrrolidone in iron-deficient and iron-replete mice.

This study evaluated the effects of iron deficiency and iron repletion on in vivo macrophage function determined by the clearance of 125I-labeled polyvinylpyrrolidone (PVP). Two experiments were done. There were four groups of C57BL/6 female mice in experiment 1: the iron-deficient (ID), pair-fed (PF), control (C) and the high iron (HI) groups. In experiment 2, there were three ID groups (severe to moderate anemia), three PF, one C and four ID groups that were fed adequate iron for 14 (R-14), 7 (R-7), 3 (R-3) days before or on the day of PVP injection (R-0). The overall rate of PVP clearance from blood was lower in ID than in C or PF groups. This clearance is expressed by a constant, K, calculated from natural log (ln) of the cpm and the time postadministration of PVP that blood was drawn. The theoretical individual macrophages function (alpha PVP), derived from K and the weights of body, spleen and liver, was also lower in ID than in C or PF groups. The impairment was most severe with the most severe iron deficiency. Repletion for 7 to 15 d before PVP administration resulted in a partial correction of the clearance. Moderate undernutrition in the PF group had no effect.

Animals↗
PubMed1986

The preparation and physicochemical characterization of an injectable form of reconstituted, glutaraldehyde cross-linked, bovine corium collagen.

Pepsin-solubilized bovine corium collagen was purified, reconstituted, and treated with various levels of glutaraldehyde. Treatment of suspensions of fibrillar collagen with low concentrations of glutaraldehyde appeared to have little effect on the gross morphology of fibrils, as judged by electron microscopy, but did have a significant impact on their physicochemical stability. Fibrillar collagen treated with glutaraldehyde at a concentration equal to or greater than 0.0075% demonstrated significant decreases in neutral solubility at elevated temperatures as compared to noncross-linked controls. Differential scanning calorimetry provided a convenient and quantitative means to correlate increases in melting temperature with increases in glutaraldehyde treatment concentration. Fibrillar collagen cross-linked with glutaraldehyde concentrations as low as 0.0075% demonstrated a significantly greater resistance to proteolytic degradation than did noncross-linked fibrillar collagen samples. The residual, extractable aldehyde content of such preparations was between 1 and 3 ppm. Rheological measurements on such cross-linked suspensions demonstrated that they were non-Newtonian, shear-thinning fluids, and that they were two- to threefold more viscous than corresponding preparations of noncross-linked collagen.

Amino Acids↗
PubMed1986

Thyroxine-binding prealbumin, overnutrition and apolipoprotein A1.

Thyroxine-binding prealbumin (TBPA) seems to be more useful than other biochemical markers for the detection of subclinical protein-energy malnutrition. Accordingly, one can question whether its sensitivity to nutritional supply could be used in healthy populations for the discrimination of groups with low or high energy intakes; if such were the case, could TBPA serve as an index of overnutrition? In order to answer these questions, we measured TBPA circulating levels in three groups of healthy French subjects from a working population, with relatively low, medium or high levels of energy intake. We also observed the correlations of this protein with nutrient intakes and with some biological parameters related to the general nutritional status of the subjects. The observed figures did not support the hypothesis that TBPA could be used to discriminate healthy subjects with relatively low or high energy intake nor as an index of overnutrition. This study disclosed a positive relation of TBPA with alcohol consumption and related parameters such as body mass index or gamma-glutamyl transferase as well as a negative one with alpha 2-globulin and gamma-globulin. Other investigators have found similar results in chronic alcoholics, surgical patients, or patients suffering from severe illnesses such as cancer. Here, the study population consisted of adult men, neither undernourished nor suffering from any severe pathology and who could not be considered excessive drinkers. Positive relations were also observed between TBPA and apolipoprotein A1 and HDL cholesterol levels, which are negatively associated with coronary heart disease risk.

Adult↗
PubMed1986

Immunity to leprosy. III. The in vitro induction of B lymphocyte proliferation by mycobacteria.

The development of murine proliferative response assays has been initiated to begin to evaluate T-lymphocyte responses to the antigens of Mycobacterium leprae. In this study, M. leprae and 13 related strains of mycobacteria have been tested for stimulatory effects in proliferation assays using murine spleen, thymus or lymph node cultures. A number of mycobacteria were found to directly stimulate the proliferation of spleen and lymph node cells of all mouse strains tested including C3H/HeJ mice. Thymocyte cultures showed no response. The mitogenic effects of mycobacteria in spleen cultures were not dependent upon the presence of T cells or adherent cells, and resulted in the production of antibody-forming cells. Thus, these bacteria acted as polyclonal B-cell mitogens and could be readily distinguished from the lipopolysaccharide of Gram-negative bacteria by their mitogenic activity on C3H/HeJ spleen cells. The species of mycobacteria which exhibit direct mitogenic effects in spleen and lymph node cultures are a particular problem when specific immune responses to the antigens of these bacteria are compared. Such comparisons are necessary if in vitro assays are to be used to determine the nature of crossreactive antigens between M. leprae and other mycobacteria.

Animals↗
PubMed1985

A simplified method for the preparation of rat thyroxine-binding prealbumin. Factors influencing its circulating level.

Rat thyroxine-binding prealbumin (TBPA) was isolated in three simple steps by means of a serum precipitation by a 5% phenol solution and two consecutive semi-preparative polyacrylamide gel electrophoreses. The overall yield was 15% and the TBPA preparation contained less than 1% impurities. In addition a monospecific antiserum was raised in the rabbit. In polyacrylamide gel, rat TBPA, as with its human counterpart, migrated anodally to albumin while in agarose gel, its electrophoretic mobility was similar to that of albumin. Serum TBPA measured in adult male Wistar rats did not exhibit a circadian rhythm. However, a significant 13% decrease was observed between 9 and 15 h, followed by the restoration of the initial value by 21 h. TBPA concentration was measured in 1-, 15- and 28-day-old male and female pups as well as in adult rats. The level of this protein increased from 1 to 28 days of age and did not display any sexual difference. Yet, while TBPA concentrations in adult males were similar to those recorded in the 28-day-old pups, for adult females, they returned to the levels measured in the 1-day-old pups.

Age Factors↗
PubMed1985

Collagen fibrillogenesis in vitro: a characterization of fibril quality as a function of assembly conditions.

Pepsin-solubilized bovine corium collagen was reconstituted by rapid neutralization in dilute phosphate buffer at temperatures ranging from 10 degrees C-25 degrees C. The resultant fibrils were harvested by centrifugation and resuspended in physiological buffer to a constant protein concentration. The optical density of such suspensions, measured at 410 nm in a 1 mm path length cuvette, exhibited a strong inverse correlation with temperature of fibrillogenesis. The absorbance values of fibrillar suspensions prepared from intact collagen were greater than those observed with suspensions prepared from pepsin-solubilized collagen under similar conditions and demonstrated a reduced dependence on temperature of fibril assembly. The nature of the variation in opacity of fibrillar suspensions prepared from pepsin-solubilized material was further investigated using transmission electron microscopy, trypsin sensitivity, SDS gel electrophoresis and polarimetry. Reconstitution conditions that favored more rapid precipitation (e.g., higher incubation temperatures) tended to produce fibril suspensions of lower opacity (translucent). These translucent suspensions exhibited fibrils that were small in diameter when compared to fibril suspensions of higher opacity. Translucent preparations also contained higher levels of a trypsin sensitive, early melting component and displayed a higher proportion of peptides migrating faster than alpha 2(I) on SDS polyacrylamide gels. Collagen preparations depleted of the early melting component continued to demonstrate the correlation between increased temperature and decreased fibrillar opacity, suggesting that the two phenomena were independent. It is proposed that the unstable components are nicked or shortened collagen helices, presumably generated by pepsinization or the action of endogenous proteases of the bovine corium, which are differentially incorporated into fibrils depending on the conditions of fibril assembly.

Animals↗
PubMed1985

Thymulin (Zn-facteur thymique serique) activity in anorexia nervosa patients.

Thymulin (or FTS-Zn) a well-defined thymic hormone was studied in fifteen female patients hospitalized for anorexia nervosa. The circulating hormone was measured together with the plasma levels of thyroid hormones, cortisol and zinc. Thymulin activity determined by the rosette assay was significantly reduced in the anorexia nervosa patients compared to sex- and age-matched healthy control subjects. The patients were characterized by very depressed plasma levels of triiodothyronine (T3) but exhibited normal concentrations of thyroxine (T4), thyroxine-binding globulin (TBG), cortisol and zinc. The distribution of their peripheral lymphocyte cells into several subsets was not affected. The observed decrease of thymulin activity in this illness might be the consequence of thymic atrophy secondary to malnutrition and/or hormonal disturbances. Our results suggested that the fall in thymulin level might explain the variability of cellular immune responses in anorexia nervosa patients and occurrence of energy when their weight loss is far advanced.

Adolescent↗
PubMed1985

Central nervous system echovirus infection in Bruton's X-linked hypogammaglobulinemia.

A patient with Bruton's X-linked hypogammaglobulinemia, who developed the typical syndrome associated with systemic echovirus 3 infection whilst on routine intramuscular gammaglobulin replacement therapy, is described. Following regular infusions of specific antibody-containing plasma from his spouse, he has shown sustained clinical improvement over a period of two years, and is, therefore, one of the very rare cases with this syndrome to survive for more than a few months.

Adolescent↗
PubMed1985

Variations in plasma thyroxine-binding prealbumin (TBPA) in relation to other circulating proteins in post-operative patients during rapid oral refeeding.

Variations in plasma thyroxine-binding prealbumin (TBPA) were investigated in 15 well-nourished patients who underwent minor orthopaedic surgery and resumed normal oral feeding on the first post-operative day. TBPA fluctuations were analysed together with those of other nutritional and inflammatory markers including albumin (ALB), some acute-phase reactant proteins, C-reactive protein (CRP), orosomucoid also named alpha 1-acid-glycoprotein (alpha 1GP), alpha 1-antitrypsin (alpha 1AT) as well as cortisol and haematocrit. Measurements were conducted the day before operation, after the administration of anaesthesia, 2 h after the patient regained consciousness and then daily for a period of one week (days 1 to 7). Assays showed that TBPA and ALB levels began to decline by day 1 reaching minimum values by day 3 (with 35 and 15 per cent total decreases respectively compared to the initial levels). CRP levels began to rise on day 1 reaching maximum levels by day 2, alpha 1 GP and alpha 1 AT started to increase on day 1 and 2 respectively and displayed maximum concentrations by day 3. Cortisol, on the other hand, showed a rapid, yet short-lived increase after the patient regained consciousness on the day of operation. Haematocrit levels decreased from day 1 to day 3 and these low values were maintained until the end of the study. Aside from cortisol and CRP, the initial levels of the other parameters were not yet restored by day 7. These results show that despite an early return to normal oral feeding in post-operative patients, the commonly observed pattern of variation in TBPA levels persisted, indicating that such a pattern seems to be mainly influenced by stress-induced post-operative responses rather than by nutritional supply.

Adolescent↗
PubMed1984

In vivo and in vitro studies of thymulin in marginally zinc-deficient mice.

Thymulin (or serum thymic factor, FTS-Zn), a well-defined thymic hormone previously shown to be a nonapeptide binding the metal zinc, was studied in mice subjected to a long-term marginally Zn-deficient diet. In spite of the absence of thymic atrophy, we observed a significant decrease in the serum levels of thymulin as early as two months after the onset of treatment. However, these levels could be consistently restored after in vitro addition of ZnCl2. The analysis of thymuses from Zn-deficient mice showed that, despite the apparently normal network of epithelial cells, there was a progressive increase in the number of thymulin -containing cells (assessed by immunofluorescence with anti- thymulin monoclonal antibodies) that was already significant after two months of treatment. These results are in keeping with those of previous investigators, showing a specific, altered, thymic endocrine function following Zn deprivation. Nonetheless, our results strongly suggest that the nonactive Zn-deprived peptide is secreted under these experimental conditions. Furthermore, the fact that the augmented numbers of thymulin -containing cells were observed in the thymuses following a decrease in the peripheral thymulin (biologically active) brings further evidence for the existence of a feedback mechanism for the secretion of this hormone.

Animals↗
PubMed1984

Corticosterone availability in male rats at rest and during shock avoidance: differences among individuals, temporal patterns and effects of dexamethasone.

Repeated measurement of the time-integral of interstitial fluid free corticosterone concentration (corticosterone availability) under home-cage conditions, during exposure to recently unfamiliar apparatus, and during active shock avoidance over 3 days, demonstrated extreme stability within individuals, and consistent differences among individuals, in corticosterone availability under home-cage conditions. These consistent differences among individuals were preserved, while mean levels were doubled, during exposure to apparatus and during shock avoidance after treatment with dexamethasone. However, this persistent pattern of differences among individuals was not apparent during shock avoidance in the absence of dexamethasone. Shock avoidance provoked up to fourfold increases in corticosterone availability. Repeated measurements over 3 days showed consistent hour-to-hour increases within days and a gradual decline over days. Dexamethasone given 4 h before shock avoidance resulted in corticosterone availability intermediate between that in home-cage and that in the previous shock-avoidance session. The situation-dependent loss of consistent interindividual differences is proposed to signal a qualitative change in regulation of corticosterone availability within individuals, and a tactic for using inter-individual differences to study some aspects of complex regulatory systems is suggested. The hour-to-hour increase in corticosterone availability during shock avoidance may be attributable to slow achievement of full adrenal output; the decline over days may be due to behavioural factors.

Animals↗
PubMed1983

A convenient equilibrium separation method for competitive protein-binding assay of corticosterone in rat serum.

Competitive protein-binding assays for corticosterone have typically employed adsorption methods for separation of free and bound ligand. Such methods often impose inconveniently strict limits upon incubation time and temperature, due to the necessity of minimizing the progressive loss of bound ligand to the adsorbent. This paper describes a convenient equilibrium assay method in which a centrifugable ion-exchange medium, DEAE-cellulose, is used to separate the corticosteroid binding globulin of rat serum and ligand bound to it, from free ligand. This method allows great latitude in incubation time and temperature, and is therefore very convenient for processing large numbers of samples. An assay optimized for use over the 50-1000 pg range showed midrange precision averaging 12% c.v., an interassay variation of 15%, and high specificity.

Animals↗
PubMed1983

Early nutritional experiments: effects on the humoral and cellular immune responses in mice.

Studies were carried out to determine the effect of varying intake during the suckling period on the immune responses of mice. Female mice were bred in litters of 4, 9 or 20 pups. Litters of nine pups were considered control groups. Overfeeding (litters of 4) during this period did not change the serum protein profile nor the humoral and cellular immunity of the weanling mice, as judged by their plaque-forming cell responses to SRBC and lymphocyte stimulation in vitro by Con A or LPS. Conversely, mice bred in large litters showed, at weaning, decreased serum levels of albumin and alpha-globulins but did not exhibit marked alterations of their immune responses, although they were in a severe state of protein-energy deficiency. After weaning, feeding a normal diet ad libitum normalized all the altered parameters tested in the malnourished mice. However, when malnutrition was followed by intermittent feeding, the studied immunological functions were significantly affected: the humoral, as well as the cell-mediated immune responses were depressed. These observed alterations were not related to changes in the levels of serum corticosterone or zinc. Our findings suggested that differences in the length of dietary deficiency rather than its severity may explain some of the conflicts in reports on functional immune tests in protein-energy malnutrition.

Aging↗