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Biomedical subjects

G Thomas

Publications and source records attributed to G Thomas.

At least 199 records · Page 11Linked to original sources

Investigation of different ontogenetic stages of Raillietiella sp. (Pentastomida: Cephalobaenida): the midgut in nutrition and digestion.

The midgut of Raillietiella sp. was investigated ultrastructurally in different ontogenetic stages from the intermediate (cockroach) and the final host (small lizards). In the embryo the midgut anlage is an accumulation of cells filled with glycogen granules. During embryogenesis the cells organize and form a narrow tube. During postembryogenesis the contribution of the midgut to the alimentary tract rises considerably from the first larva to the adult parasites. In all stages the midgut is not divided into zones; however, two cell types (crystal and noncrystal cells) are distinguishable. Digestion takes place extracellularly. The main storage product of the midgut cells and the surrounding muscle cells is glycogen. A slight cyclic course of the digestive process is discernible.

Animals↗

Investigation of different ontogenetic stages of Raillietiella sp. (Pentastomida: Cephalobaenida): ionical glands.

The ionic glands of Raillietiella sp. were investigated ultrastructurally in different ontogenetic stages. Modifications of the ultrastructure, number, and distribution of ionic glands were observed after the invasion of the primary larvae into the invertebrate intermediate host and after the invasion of the infective larvae into the vertebrate final host. On the basis of a comparison of the ultrastructure of ionic glands in Raillietiella sp. with that of other pentastomids described in the literature, a general conformity of pentastomid ionic glands can be stated. We propose a defined nomenclature that is integrated into the complete nomenclature of the pentastomid gland system and summarize the synonyms of the ionic glands. Ultrahistochemical chloride detection by energy-dispersive X-ray analysis shows the function of the ionic glands for chloride regulation. Remarkably, in Raillietiella sp., ionic glands also exist in the female genital system. Ionic glands with two central cells occur in cephalobaenids. The existence of ionic glands in Cephalobaena tetrapoda, which has thus far been doubted, can be proved.

Animals↗

Cissampelos sympodialis Eichl. leaf extract increases the production of IL-10 by concanavalin-A-treated BALB/c spleen cells.

The effect of the aqueous fraction of the ethanol extract of Cissampelos sympodialis Eichl. (Menispermaceae) leaves (AFL) on Concanavalin-A (Con-A)-activated spleen cell proliferation and cytokine (IL-2, IL-4, IL-10 and IFN-gamma) secretion were analyzed. BALB/c spleen cells were treated, in vitro, with different concentrations, ranging from 6.25 to 400 microg/ml of AFL either in the presence or the absence of 5 microg/ml of the mitogen Con-A. It was observed that concentrations of the AFL higher then 50 microg/ml were toxic to the cells and concentrations ranging from 6.25 to 50 microg/ml decreased the lymphocyte proliferative response in the presence of the mitogen. This inhibition of mitogen induced proliferation was not reverted by the addition of exogenous recombinant IL-2. The AFL did not significantly inhibit IL-2 secretion. In the presence of AFL there was a reduction in the levels of secreted IFN-gamma while the production of both IL-10 and IL-4 were increased. AFL did not induce the production of any of the cytokines analyzed, in the absence of Con-A. It is suggested that increased IL-10 production down regulates IFN-gamma secretion and T cell proliferative responses.

Animals↗

Target of rapamycin (TOR): balancing the opposing forces of protein synthesis and degradation.

Mitogenic and nutritional signals must be integrated for a cell to grow. The target of rapamycin (TOR) is emerging as an effector for signals which indicate to the cell whether the external environment is conducive for growth. Use of the immunosuppressant rapamycin, a bacterial macrolide, has been instructive in identifying potential signaling components downstream of TOR, leading to the observation that both protein synthesis and turnover are under TOR control. The central issues concerning TOR are the identification of the proliferative and anti-proliferative signals which mediate its function and the mechanisms by which these signals are transduced to downstream molecules.

Animals↗

Bi-cycling the furin pathway: from TGN localization to pathogen activation and embryogenesis.

Furin is a secretory pathway endoprotease that catalyses the maturation of a strikingly diverse group of proprotein substrates, ranging from growth factors and receptors to pathogen proteins, in multiple compartments within the trans-Golgi network (TGN)/endosomal system. This review focuses on recent developments in the biochemistry and cell biology of the endoprotease, including the mechanism of TGN localization, phosphorylation-dependent regulation of protein traffic, and novel insights into early embryogenesis, extracellular matrix formation and pathogen virulence.

Amino Acid Sequence↗

The meaning of early mortality after CABG.

OBJECTIVE: Investigations of early mortality after coronary artery bypass grafting (CABG) are predominantly based on 30-day mortality or hospital mortality. The advantages, disadvantages, and usefulness of hospital mortality and 30-day mortality analyses to investigate the early risk after CABG are evaluated. METHODS: A total of 4985 patients underwent isolated CABG from June 1988 to June 1997. A follow-up was performed 180 days after CABG (response rate: 98.6%). RESULTS: The mean hospital stay was 13.5+/-9.6 days, the range was 0 to 142 days (25% quartile, 9 days; median, 12 days; 75% quartile, 15 days). The hospital mortality was 5.3%. The 30-day mortality was 5.6%. The non-parametric Kaplan-Meier curve of the time interval 0-180 days postoperatively proves the persistence of the still decreasing behaviour of the survival curve beyond the 30th day until about the 60th postoperative day. Stratified by era of operation, the 'early phase' after CABG seems to be prolonged beyond 30 days at least for the more recent operation era since 1991. Risk stratification proves that the higher the risk group, the more the early phase tends towards a prolongation. CONCLUSIONS: The hospital mortality reflects institutional habits concerning postoperative patient care. Therefore, a systematic underestimation of early mortality is likely. In contrast to hospital stay, the evaluation of 30-day mortality requires a follow-up procedure but allows interinstitutional comparisons. Nevertheless, 30-day mortality systematically underestimates the early risk, at least in the more recent CABG period. So, a standardized evaluation of a longer time period (p.e. 180 days) is recommended.

Coronary Artery Bypass↗

Ideals in intimate relationships.

This research examined lay relationship and partner ideals in romantic relationships from both a social-cognitive and an evolutionary perspective. Studies 1 and 2 revealed that the qualities of an ideal partner were represented by 3 factors (partner warmth-trustworthiness, vitality-attractiveness, and status-resources), whereas the qualities of an ideal relationship were represented by 2 factors (relationship intimacy-loyalty and passion). A confirmatory factor analysis in Study 3 replicated these factor structures but found considerable overlap across the partner and relationship dimensions. Studies 4 and 5 produced convergent and discriminant validity evidence for all 5 factors. Study 6 indicated that the higher the consistency between the ideals and related assessments of the current partner and relationship, the more positively the current relationship was evaluated.

Adolescent↗

Tracheal relaxant activity of cissaglaberrimine and trilobinine, two aporphinic alkaloids from Cissampelos glaberrima.

In the present work we studied the relaxant effect of two aporphinic alkaloids isolated from the roots barks of Cissampelos glaberrima St. Hil. (Menispermaceae), (+)-cissaglaberrimine (CGE; a tertiary alkaloid) and (+)-trilobinine (TBE; a quaternary alkaloid). In guinea-pig tracheal preparations, CGE and TBE reduced the spontaneous tone and inhibited the contractions induced by carbachol and histamine. TBE was 6 times more potent than CGE in reducing the spontaneous tone and it was also 1.5 times more potent in antagonising the effects of carbachol and histamine. The inhibitory effect of CGE in contractions induced by histamine was not attenuated in the presence of timolol (10 microM). However, in the same experimental conditions, timolol almost completely abolished the inhibitory effect of TBE. These results showed that the relaxations induced by TBE were dependent on the activation of beta 2-adrenoceptors, while the mechanism involved in relaxations induced by CGE remains to be determined.

Alkaloids↗

Influence of follow-up response on risk-factor analysis.

BACKGROUND: Long-term analyses after coronary artery bypass grafting (CABG) are used to investigate therapeutical options and factors influencing the natural course of ischemic heart disease. In general, long-term studies require a follow-up. Dependent on the interval between the intervention and the follow-up procedure a certain amount of patients is lost to follow-up. The aim of the present study was to examine the influence of incomplete follow-up on conclusions regarding the postoperative patient outcome. For the investigation, the same statistical methods were applied to the data accumulated by the 70% and by the 90% responses. METHODS: 2012 patients underwent isolated CABG between June 1988 and December 1992. For data acquisition, tools of the HVMD (Heidelberger Verein für multizentrische Datenanalyse e.V.) were used. Analyses were performed using tools of SAS (Statistical Analysis Systems, Inc.). The parametric, time-adjusted hazard function method was employed. A first follow-up questionnaire, was distributed six months after operation with a 97.8% response. In February 1997 the same questionnaire was sent to patients and their general practioners. The primary response to that was 68.9% (approximately 70%). Then another mailing of the same questionnaire and phone calls to patients and their home doctors raised the response to 93.7% (approximately 90%). RESULTS: The mean follow-up was 1378 days in the group with 70% response and 1682 days in the group with 90% response. The parametric, time-adjusted hazard function showed a very similar pattern of factors in the early phase of both groups. In the 90% response group, the intermediate phase reached a higher relative influence than in the 70% response group. The relative influence of the late phase showed an inverse pattern. In the multivariate analysis most of the variables which had been identified by the 70% response model reappeared in the 90% response model. However, there were some potentially important and interesting differences. CONCLUSIONS: The results indicate the necessity to carefully consider the acceptance of incomplete follow-up for differentiated risk adjustment.

Coronary Artery Bypass↗

Core beliefs in anorexic and bulimic women.

There is research evidence to suggest the presence of dysfunctional cognitions in anorexia nervosa and bulimia nervosa that are not related to food, weight, or shape. These maladaptive cognitions have not been addressed by the conventional cognitive behavioral models of etiology or therapy. This study aimed to assess the impact of unhealthy core beliefs on eating disorders and their symptoms. Twenty restricting anorexics, 10 bulimic anorexics, 27 bulimics, and 23 normal controls completed Young's Schema Questionnaire. Eating behaviors and attitudes were also measured. The results indicate that both anorexic and bulimic women had significantly higher levels of unhealthy core beliefs than comparison women, but the clinical groups only differed on one individual core belief (entitlement). However, there were different patterns of association between core beliefs and eating psychopathology in anorexic and bulimic women. It is suggested that future clinical practice should incorporate core beliefs as a potential element in the assessment and treatment of eating disorders.

Adolescent↗

p70(S6K) controls selective mRNA translation during oocyte maturation and early embryogenesis in Xenopus laevis.

In mammalian cells, p70(S6K) plays a key role in translational control of cell proliferation in response to growth factors. Because of the reliance on translational control in early vertebrate development, we cloned a Xenopus homolog of p70(S6K) and investigated the activity profile of p70(S6K) during Xenopus oocyte maturation and early embryogenesis. p70(S6K) activity is high in resting oocytes and decreases to background levels upon stimulation of maturation with progesterone. During embryonic development, three peaks of activity were observed: immediately after fertilization, shortly before the midblastula transition, and during gastrulation. Rapamycin, an inhibitor of p70(S6K) activation, caused oocytes to undergo germinal vesicle breakdown earlier than control oocytes, and sensitivity to progesterone was increased. Injection of a rapamycin-insensitive, constitutively active mutant of p70(S6K) reversed the effects of rapamycin. However, increases in S6 phosphorylation were not significantly affected by rapamycin during maturation. mos mRNA, which does not contain a 5'-terminal oligopyrimidine tract (5'-TOP), was translated earlier, and a larger amount of Mos protein was produced in rapamycin-treated oocytes. In fertilized eggs rapamycin treatment increased the translation of the Cdc25A phosphatase, which lacks a 5'-TOP. Translation assays in vivo using both DNA and RNA reporter constructs with the 5'-TOP from elongation factor 2 showed decreased translational activity with rapamycin, whereas constructs without a 5'-TOP or with an internal ribosome entry site were translated more efficiently upon rapamycin treatment. These results suggest that changes in p70(S6K) activity during oocyte maturation and early embryogenesis selectively alter the translational capacity available for mRNAs lacking a 5'-TOP region.

Amino Acid Sequence↗

Protein kinase B localization and activation differentially affect S6 kinase 1 activity and eukaryotic translation initiation factor 4E-binding protein 1 phosphorylation.

Recent studies indicate that phosphatidylinositide-3OH kinase (PI3K)-induced S6 kinase (S6K1) activation is mediated by protein kinase B (PKB). Support for this hypothesis has largely relied on results obtained with highly active, constitutively membrane-localized alleles of wild-type PKB, whose activity is independent of PI3K. Here we set out to examine the importance of PKB signaling in S6K1 activation. In parallel, glycogen synthase kinase 3beta (GSK-3beta) inactivation and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation were monitored as markers of the rapamycin-insensitive and -sensitive branches of the PI3K signaling pathway, respectively. The results demonstrate that two activated PKBalpha mutants, whose basal activity is equivalent to that of insulin-induced wild-type PKB, inhibit GSK-3beta to the same extent as a highly active, constitutively membrane-targeted wild-type PKB allele. However, of these two mutants, only the constitutively membrane-targeted allele of PKB induces S6K1 activation. Furthermore, an interfering mutant of PKB, which blocks insulin-induced PKB activation and GSK-3beta inactivation, has no effect on S6K1 activation. Surprisingly, all the activated PKB mutants, regardless of constitutive membrane localization, induce 4E-BP1 phosphorylation and the interfering PKB mutant blocks insulin-induced 4E-BP1 phosphorylation. The results demonstrate that PKB mediates S6K1 activation only as a function of constitutive membrane localization, whereas the activation of PKB appears both necessary and sufficient to induce 4E-BP1 phosphorylation independently of its intracellular location.

Adaptor Proteins, Signal Transducing↗

p70(s6k) integrates phosphatidylinositol 3-kinase and rapamycin-regulated signals for E2F regulation in T lymphocytes.

In T lymphocytes, the hematopoietic cytokine interleukin-2 (IL-2) uses phosphatidylinositol 3-kinase (PI 3-kinase)-induced signaling pathways to regulate E2F transcriptional activity, a critical cell cycle checkpoint. PI 3-kinase also regulates the activity of p70(s6k), the 40S ribosomal protein S6 kinase, a response that is abrogated by the macrolide rapamycin. This immunosuppressive drug is known to prevent T-cell proliferation, but the precise point at which rapamycin regulates T-cell cycle progression has yet to be elucidated. Moreover, the effects of rapamycin on, and the role of p70(s6k) in, IL-2 and PI 3-kinase activation of E2Fs have not been characterized. Our present results show that IL-2- and PI 3-kinase-induced pathways for the regulation of E2F transcriptional activity include both rapamycin-resistant and rapamycin-sensitive components. Expression of a rapamycin-resistant mutant of p70(s6k) in T cells could restore rapamycin-suppressed E2F responses. Thus, the rapamycin-controlled processes involved in E2F regulation appear to be mediated by p70(s6k). However, the rapamycin-resistant p70(s6k) could not rescue rapamycin inhibition of T-cell cycle entry, consistent with the involvement of additional, rapamycin-sensitive pathways in the control of T-cell cycle progression. The present results thus show that p70(s6k) is able to regulate E2F transcriptional activity and provide direct evidence for the first time for a link between IL-2 receptors, PI 3-kinase, and p70(s6k) that regulates a crucial G1 checkpoint in T lymphocytes.

Carrier Proteins↗

Issues related to the experimental design and subsequent statistical analysis of in vivo and in vitro comet studies.

A wide range of experimental designs are used in investigations using the Comet assay. The statistical issues associated with this assay are however not particularly unusual or difficult. It is important however to recognize that the sample rather than the cell is the experimental unit. Statistical analyses based upon measures from the individual cells can lead to serious misinterpretation of results. Interpretation of the results of the assay should be related to identifying changes of biological importance rather than relying solely on the P values of specific statistical tests.

Animals↗