[Childhood obesity. Treatment of severe obesity].
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Adolescent↗
Biomedical subjects
M Morin
Publications and source records attributed to M Morin.
[An information tool: the CD photos].
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Audiovisual Aids↗
Insulin-mediated targeting of phosphatidylinositol 3-kinase to GLUT4-containing vesicles.
Phosphatidylinositol (PI) 3-kinase is hypothesized to be a signaling element in the acute redistribution of intracellular GLUT4 glucose transporters to the plasma membrane in response to insulin. However, some receptors activate PI 3-kinase without causing GLUT4 translocation, suggesting specific cellular localization may be critical to this PI 3-kinase function. Consistent with this idea, complexes containing PI 3-kinase bound to insulin receptor substrate 1 (IRS-1) in 3T3-L1 adipocytes are associated with intracellular membranes (Heller-Harrison, R., Morin, M. and Czech, M. (1995) J. Biol. Chem. 270, 24442-24450). We report here that in response to insulin, activated complexes of IRS-1.PI 3-kinase can be immunoprecipitated with anti-IRS-1 antibody from detergent extracts of immunoadsorbed GLUT4-containing vesicles prepared from 3T3-L1 adipocytes. The targeting of PI 3-kinase to rat adipocyte GLUT4-containing vesicles using vesicles prepared by sucrose velocity gradient ultracentrifugation was also demonstrated. Insulin treatment caused a 2.3-fold increase in immunoreactive p85 protein in these GLUT4-containing vesicles while anti-p85 immunoprecipitates of PI 3-kinase activity in GLUT4-containing vesicle extracts increased to a similar extent. HPLC analysis of the GLUT4 vesicle-associated PI 3-kinase activity showed insulin-mediated increases in PI 3-P, PI 3,4-P2, and PI 3,4,5-P3 when PI, PI 4-P, and PI 4,5-P2 were used as substrates. Our data demonstrate that insulin directs the association of PI 3-kinase with GLUT4-containing vesicles in 3T3-L1 and rat adipocytes, consistent with the hypothesis that PI 3-kinase is involved in the insulin-regulated movement of GLUT4 to the plasma membrane.
3T3 Cells↗
Thyroid hormone and the gut: selective transcriptional activation of a villus-enterocyte marker.
BACKGROUND: Thyroid hormone (T3) is an important regulator of gut mucosal growth, differentiation, and barrier function, but its mechanism of action in the gastrointestinal tract is largely unknown. The present studies were carried out to define the molecular mechanisms by which T3 alters gut gene expression. METHODS: In vivo: Adult, male, Sprague-Dawley rats were given three daily injections (intraperitoneal) of either saline solution or 30 micrograms/kg triiodothyronine. Small intestinal tissues were harvested, and Northern blot analyses were performed by using specific radiolabeled cDNA probes. In vitro: HT-29 cells were transfected with reporter plasmids and treated with or without T3, and chloramphenicol acetyltransferase activity was measured. RESULTS: The T3-induced changes in enterocyte gene expression occurred in villus enterocytes and not in crypt cells and were independent of food intake. Northern analyses with an intron-specific probe revealed that the T3 induction in intestinal alkaline phosphatase (IAP) expression occurs at the level of transcription. Transient transfection assays revealed no T3-induced changes under basal conditions but marked increases (sixfold, p < 0.001) when a T3-receptor (TR beta-1) plasmid was cotransfected. Furthermore, T3 was found to induce greater IAP reporter gene activity in differentiated (+ sodium butyrate) compared with undifferentiated HT-29 cells. CONCLUSIONS: T3 induces IAP expression at the level of gene transcription. Both in vivo and in vitro, IAP transcriptional activation occurs to a greater extent in differentiated enterocytes than in undifferentiated crypt cells. Transactivation of the IAP gene by T3 is mediated via a DNA cis-element(s) located within the 2.4 kb segment present in the reporter gene.
Animals↗
Role of different lymphoid tissues in the initiation and maintenance of DNA-raised antibody responses to the influenza virus H1 glycoprotein.
Antibody responses in mice immunized by a single gene gun inoculation of plasmid expressing the influenza virus H1 hemagglutinin and in mice immunized by a sublethal H1 influenza virus infection have been compared. Both immunizations raised long-lived serum responses that were associated with the localization of antibody-secreting cells (ASC) to the bone marrow. However, the kinetics of these responses were 4 to 8 weeks slower in the DNA-immunized than in the infection-primed mice. Following a gene gun booster, the presence of ASC in the inguinal lymph nodes, but not in other lymph nodes, revealed gene gun responses being initiated in the nodes that drain the skin target site. Both pre- and postchallenge, the DNA-immunized mice had 5- to 10-times-lower levels of antibody and ASC than the infection-primed mice.
Animals↗
Posterior rounded high-intensity zone on magnetic resonance images as a sign of painful disk. Report of a case.
In 1992, Aprill and Bogduk reported that a rounded high-intensity zone was seen in the posterior part of the annulus fibrosus on T2-weighted images of at least one of the last intervertebral disks in 29% of 500 patients with low back pain. This image was correlated with Dallas stage 4 disk disease and with reproduction of the spontaneous pain during discography coupled with computed tomography. We report a case and discuss the value of this image.
Adult↗
[Effects of dose rate on carcinogenesis after exposure of rats to low doses of neutron irradiation].
In this experiment we compared the efficiency of fission neutrons of californium 252 at doses of 25 or 53 mGy in function of the dose rate. Two groups of male Sprague-Dawley rats were exposed at 100 or 420 days of age to fission neutrons with dose rates of 950 or 760 microGy/h for 26 or 33 h, and 2 other groups were irradiated over a year from 3 months to 15 months of age with dose rates of 3.58 or 7.72 microGy/h. The 4 groups of animals were compared with a control group of 501 rats. The reduction of effectiveness on cancer induction that we have previously shown at low dose rate with rats exposed to gamma rays or to alpha particles was not observed for low dose rate exposure with fission neutrons.
Animals↗
Insulin regulation of membrane-associated insulin receptor substrate 1.
Insulin stimulation of 3T3-L1 adipocytes results in rapid activation of the insulin receptor tyrosine kinase followed by autophosphorylation of the receptor and phosphorylation of insulin receptor substrate 1 (IRS-1), its major substrate. The insulin receptor resides mostly at the cell surface of 3T3-L1 adipocytes under basal conditions, while about two-thirds of IRS-1 fractionates with intracellular membranes and one-third fractionates with cytosol. To test whether insulin receptor internalization is required for optimal tyrosine phosphorylation of IRS-1, 3T3-L1 adipocytes and CHO-T cells were incubated at 4 degrees C which inhibits receptor endocytosis but not its tyrosine kinase activity. Under these conditions, tyrosine phosphorylation of IRS-1 in the low density microsome fraction in response to insulin was as intense as that observed at 37 degrees C, indicating that endocytosis of insulin receptors is not necessary for tyrosine phosphorylation of IRS-1 to occur. Surprisingly, at 37 degrees C, insulin action on 3T3-L1 adipocytes progressively decreased the amount of IRS-1 protein associated with the low density microsome fraction and increased that in the cytosol. This redistribution of IRS-1 from the low density microsome fraction to the cytosol in response to insulin was accompanied by decreased electrophoretic mobility of IRS-1 on SDS-polyacrylamide gel electrophoresis. Incubation of adipocytes at 4 degrees C blocked the appearance of tyrosine-phosphorylated IRS-1 in the cytosol. Taken together, these data indicate that insulin receptors phosphorylate IRS-1 at the cell surface, perhaps in coated pits which are included in the low density microsome fraction. The results also suggest a desensitization mechanism in which the tyrosine-phosphorylated membrane-bound IRS-1, associated with signaling molecules such as phosphatidylinositol 3-kinase, is released into the cytoplasm in concert with its serine/threonine phosphorylation.
3T3 Cells↗
Dark photorefractive spatial solitons and photorefractive vortex solitons.
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Journal Article↗
Assessing vascular dementia.
Vascular dementia is the most common cause of dementia in the elderly after Alzheimer's disease. Many forms of vascular dementia have been described: multi-infarct dementia, lacunar dementia, Binswanger's subcortical encephalopathy, cerebral amyloid angiopathy, white matter lesions associated with dementias, single infarct dementia, dementia linked to hypoperfusion and haemorrhagic dementia. The difficulty of diagnosing vascular dementia must not be underestimated and an international consensus is needed for epidemiological studies. The NINCDS-AIREN group has recently published diagnostic criteria. The State of California Alzheimer's Disease Diagnostic and Treatment Centers also proposed some which differ from the NINCDS-AIREN criteria in considering only ischaemic vascular dementia and not other mechanisms such as haemorrhagic or hypoxic lesions. Most studies stress hypertension as the most powerful risk factor for all forms of vascular dementia. The incidence rate ranges from 7 per 1000 person-years in normal volunteers to 16 per 1000 person-years in hypertensive patients. No therapeutic attempt has influenced the course of the disease once the dementing condition is established. The only effective approach is preventive treatment. The objective of the SYST-EUR Vascular Dementia project is to confirm that the treatment of isolated systolic hypertension is able to reduce its incidence.
Dementia, Vascular↗
Commitment, value conflicts and role strains among French GPs in care for HIV positive patients.
A survey was carried out on a random sample of GPs in the city of Marseille. 18.5% had been involved during the past year in a regular follow-up of HIV patients. They were in charge with 79.8% of all ambulatory care of HIV+ patients. Those informally 'specialized' professionals were connected to health networks (not only hospital structures but also associations dealing with commitment in care). Socio-biographical factors, training and environmental opportunities and ideological orientations would positively relate with commitment in care. GPs who were not involved with care, would worry more about personal risk of contamination; would not believe that wearing gloves could be a sufficient protection when doing invasive procedures; would feel less at ease with HIV patients, would be more strongly in favor of coercive measures with IVDU's. Most GP's would agree to avoid drug users HIV+ patients. They would attribute to them more guilt and responsibility than to other patients. Uncertainty concerning relevant knowledge, negative attitudes towards some patients like IVDU's and anticipated difficulties to deal with ethical and relational dilemmas keep limiting GPs interest and positive motivation in care for HIV patients.
Conflict, Psychological↗
Determinants of late allograft nephrectomy.
When loss of graft function occurs more than six months after transplantation, allograft nephrectomy is not routinely performed at the time of graft failure. It is usually performed only on those patients who subsequently develop specific complications. However, little is known about the characteristics that make patients more likely to require allograft nephrectomy. The purpose of our study was to identify risk factors for the subsequent need for allograft nephrectomy in patients with graft failure occurring more than 6 months after transplantation. Forty-one patients were studied. Inclusion criteria were: loss of graft function > or = 6 months after transplantation, resumption of dialysis and initiation of weaning from immunosuppression. Thirty patients were treated with cyclosporine + prednisone +/- azathioprine and 11 with azathioprine + prednisone. Mean follow-up time was 17.8 months, ranging from 6 months to 6.1 years. Recipient age, sex and race, original renal disease, donor, donor source (cadaveric vs living related), HLA compatibility, levels of panel reactive antibodies, occurrence of initial delayed graft function, causes of graft failure and tapering of immunosuppression were similar in patients with and without allograft nephrectomy. Using univariate analysis, allograft nephrectomy was found to be significantly more frequent in patients with a history of 2 or more episodes of acute rejection than in patients with no rejection episode: 83% vs 30% (p = 0.03). In addition, allograft nephrectomy was found to be significantly more frequent if the immunosuppressive regimen included cyclosporine (62% vs 27.3%; p = 0.04). Using multivariate analysis however, the number of previous episodes of rejection was found to be the only significant predictor for allograft nephrectomy. None of the other variables considered in the multivariate analysis, including the type of immunosuppressive therapy, was identified as a significant predictor for the need to perform allograft nephrectomy. In summary, the need for late allograft nephrectomy was correlated with the number of previous episodes of acute rejection. Patients with a history of numerous rejection episodes should thus be considered more likely to require allograft nephrectomy once immunosuppression is withdrawn. Possible interventions to reduce or prevent the need for nephrectomy include more gradual tapering of immunosuppression at the time of graft failure or indefinite low-dose immunosuppressive therapy.
Adult↗
Interaction of porcine reproductive and respiratory syndrome virus with swine monocytes.
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Abortion, Veterinary↗
Carcinogenic and cocarcinogenic effects of radon and radon daughters in rats.
It has been previously established that lung cancer could be induced in rats by exposure to radon and radon daughters. Although the oat-cell carcinomas that are common in humans were not found in rats, other histological types of lung carcinomas, especially squamous cell carcinomas and primitive lung adenocarcinomas, were similar to those observed in humans. A dose-effect relationship was established for cumulative doses varying from 25 to 3000 working-level-months (WLM), which was similar for medium and high cumulative doses to that observed in uranium miners. This experimental protocol was also used to study the potential cocarcinogenic effects of other environmental or industrial airborne pollutants such as tobacco smoke, mineral fibers, diesel exhausts, or minerals from metallic mine ores that may act synergistically with radon exposure. In rats exposed to radon and tobacco smoke combined, the incidence of lung cancers was higher by a factor of 2-4 according to the cumulative radon exposure and the duration of tobacco smoke exposure. When mineral fibers were injected intrapleurally, an increased incidence of malignant thoracic tumors was observed in rats exposed to radon and fibers combined, but synergistic effects resulted in additivity. With diesel exhausts or minerals from metallic ores, a slight, nonsignificant increase in the incidence of lung carcinomas was observed compared with rats exposed to radon alone. These results demonstrated that it is possible to establish the potential cocarcinogenic action, showing either multiplicative, additive, or no effect of various environmental or industrial airborne pollutants combined with radon exposure. This radon model is valid for investigating possible interactions between two occupational exposures.
Air Pollutants↗
[Experimental study of different histologic types of pulmonary cancers induced by irradiation].
Recent epidemiologic studies suggested that some histologic types of carcinomas were preferentially induced in the lung by irradiation, whatever the mode of exposure and the radiation quality. Since smoking and other environmental airborne pollutants may be strong confounding factors in humans, we have investigated whether histological subtypes were dependent or not on the mode of exposure, in a large series of 9000 rats exposed to external and internal sources at high and low Linear Energy Transfer. Despite comparable overall risk coefficients in rats and humans, our results show that histological types are influenced not only by dose but also by radiation quality and heterogeneity of dose delivering. We suggest that extrapolation from one group to an other take this information in consideration.
Animals↗
[Relationship between irradiation and appearance of brain tumors in rats].
Sprague-Dawley rats were exposed to Co 60 irradiation (3 Gy) at different ages. Rats were distributed among sham-control (618 males and 120 females) and exposed groups: foetus (66 males and 65 females), 3 month-old (304 males), and 9 month-old (120 males and 60 females). The incidence of brain tumours was 5.3% in male control rats and nil in female control rats. Brain tumour incidence decreased in 9 month-old rats (3.3%), and increased from 6.6% in 3 month-old rats to 15.2% in male foetuses and 12.3% in female foetuses. Age at incidence of brain tumours decreased in irradiatiated animals. Astrocytomas were the more susceptible type of brain tumours to radiocarcinogenesis.
Age Factors↗
[Arterial risks in celiosurgery].
It is important to recognize exceptional vascular events in celiosurgery because of their gravity. Most occur during pneumoperitoneal manoeuvres using a Palmer needle and rarely at the insertion of the first trocar. We performed a tomodensitometric study in 200 subjects free of abdominal pathology in order to determine the distance from the umbilicus to the aortic bifurcation, their projection over the spine and the superficial relations of the large vessels to the cutaneous umbilical cover. Generally, the projections of the umbilicus, and also the aortic bifurcation, lie over L4. The distance between the skin and the large retroperitoneal vesses is generally equal to one-third of the antero-posterior abdominal diameter. In thin subjects with a flat abdomen however, this distance may be smaller, even less than 3 cm. These findings emphasize the importance of "safety" manoeuvres during celiosurgery, especially during the learning period.
Adolescent↗
The chondroitin sulfate form of invariant chain can enhance stimulation of T cell responses through interaction with CD44.
Invariant chain (Ii) is a nonpolymorphic glycoprotein that associates with major histocompatibility complex class II molecules and has been shown to mediate several functions in class II-restricted antigen presentation. A small proportion of Ii is modified by the addition of chondroitin sulfate (Ii-CS), and this form of Ii is associated with class II on the surface of antigen-presenting cells. In this report we show that expression of Ii-CS dramatically enhanced the ability of class II-positive EL4 transfectants to stimulate class II-dependent allogeneic and mitogenic T cell responses. Antibody blocking studies and the ability of CD44 to bind directly to Ii-CS suggest that Ii-CS can function as an accessory molecule during T cell responses through interactions with CD44.
Animals↗