Microscopic analysis of alpha scattering from 28Si at 40 and 45 MeV.
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Biomedical subjects
Publications and source records attributed to S Roy.
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A Gianturco type metallic stent placed in the common bile duct migrated into the duodenum. The device remains in situ, and has caused no ill-effects to date. This raises the possibility that such stents may be deployed in the gastrointestinal tract.
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BACKGROUND: The leucine-zipper c-fos has been implicated in the regulation of gene expression. We investigated the possible role of c-fos in the regulation of hepatic gene expression after sepsis. Based on previous data demonstrating that sepsis inhibits hepatic gene expression of carnitine palmitoyltransferase (CPT), we hypothesized that c-fos may play a role in the inhibition of CPT gene expression after sepsis. METHODS: We studied c-fos gene expression after peritoneal sepsis induced by cecal ligation and puncture (CLP) or sham-CLP. To investigate the possible inhibitory role of c-fos on CPT gene transcription, we investigated the effect of c-fos on c-jun-driven CPT promoter-chloramphenicol acyltransferase reporter gene expression in a HepG2 hepatoma cell cotransfection model. To investigate the possible role of cyclic adenosine monophosphate (cAMP) in the regulation of c-fos in vivo, we treated either the sham-CLP group or the CLP group with either vehicle or cAMP. RESULTS: Peritoneal sepsis in the rat model resulted in a four-fold increase in hepatic c-fos mRNA and c-fos protein. In the cotransfection model, c-fos significantly inhibited c-jun-induced chloramphenicol acyltransferase activity. Treatment with cAMP resulted in a 50% decrease in c-fos protein in either the sham-CLP or CLP group. CONCLUSIONS: We conclude that (1) sepsis increases hepatic c-fos transcription and translation, (2) c-fos inhibits c-jun-induced CPT gene expression, and (3) cAMP probably does not directly mediate the increase in c-fos after sepsis.
We have previously reported that interleukin-1-induced proliferation of thymocytes is accompanied by the appearance of [3H]morphine binding sites on these cells. In the present study, we have characterized these binding sites. They differ from classical opioid receptors in the brain in several ways, including: 1) lack of stereoselectivity; 2) relatively low affinity (Kd = 50 nM) and high capacity (Bmax = 3 pmol/mg of protein); 3) binding is strongly inhibited by Ca++, Mg++, Mn++ and Cl- ions and 4) binding is inhibited by proteinase K or E and by phospholipase A2 but not trypsin treatment of thymocyte membranes. The binding sites, which were found largely on the CD4+ subset of T-cells, also showed a preference for opioid alkaloids over peptides. These [3H]morphine binding sites may mediate a negative feedback effect on interleukin-1-induced proliferation of thymocytes in vivo.
Many HIV-infected children have neurological involvement. We present our observations in 49 cases, 58% of which had some form of clinical neurological impairment. Most of the patients affected (71%) presented with progressive encephalopathy, characterized by developmental delay with loss of acquisitions and cognitive decline, an impaired growth curve, microcephaly and corticospinal dysfunction. CT-scan imaging shows cerebral atrophy in all cases and basal ganglia calcifications in 29%. Non-specific abnormalities are found on the EEG in two-thirds of cases and in the CSF in slightly less than half the cases. Pathological studies sometime revealed HIV encephalitis or lateral corticospinal tracts degeneration. Neurological impairment secondary to vascular events, neoplasms or opportunistic infections were rare, especially when compared with the adult HIV population.
A 50 year old hypertensive man presented with acute epigastric pain associated with massive gastrointestinal bleed and died within 48 hours of admission. Autopsy revealed transmural infarction of the gut due to a long aortic dissection.
An ultrastructural study was done on 15 mixed growth hormone (GH) and prolactin (PRL)-secreting pituitary adenomas surgically removed from acromegalic patients with hyper-prolactinaemia, in order to see whether the 2 hormones were present in the same cell or in different cells. Double labelling immunogold technique was used for simultaneous ultrastructural localization of GH and PRL. It was found that each neoplastic cell in these 15 tumours (30 to 50 cells were studied in each case) contained 4 populations of granules viz., (i) granules positive for only GH; (ii) granules positive for only PRL; (iii) granules positive for both GH and PRL; and (iv) granules negative for both GH and PRL (unlabelled). Though the relative percentage of these 4 types of granules varied from cell to cell even within the same tumour, the major population (49.9 to 96%) was constituted by the mixed granules showing labelling for both GH and PRL. Almost all the cells examined from each tumour appeared to be mammosomatotrophs. Thus, the study indicated that mammosomatotroph adenomas are perhaps more common among mixed GH and PRL--secreting pituitary adenomas than previously believed. It could be important to recognize these tumours from the therapeutic point of view.
Brain tissues from 10 patients (of non-neurological disease) were studied for the presence of corpora amylacea (CA) using light microscopy (LM), immunohistochemistry (IH) for localisation of glial fibrillary acidic protein (GFAP) and transmission electron microscopy (TEM). Immunoelectron microscopy (IEM) by post-embedding technique using colloidal gold was also performed in two of these patients for more precise localisation of GFAP. Three types of immunoreactivity were noted by IH under LM; some CA were completely negative for GFAP (type III), while others showed positivity, which was either diffuse (type I) or confined to the periphery (rim positivity-type II). TEM showed variable sizes in electron dense material in the centre associated with different amounts of glial filaments (GFs) at the periphery. Thus the different types of IH staining appeared to corroborate with the presence and amount of GFs in CA. The sensitive technique of IEM confirmed the presence of GFAP in all CA irrespective of their IH typing at LM. It is suggested that CA formation in astrocytes is associated with progressive fragmentation and disintegration of GFs with resulting increase in the accumulation of electron dense GFAP-negative material. As more and more of GFs get incorporated and disintegrated, it results in increase in the size of the CA. Thus, the present study clearly demonstrates that GFAP in the GFs contributes to the composition of CA.
This study was designed to investigate the potential of the Gianturco-Rosch Z stent in the alimentary canal, using the rabbit esophagus as the animal model. Single stents were implanted in four animals, which were followed up for predetermined periods, lasting from 48 hours to 6 weeks. All the stents remained in place. A florid tissue reaction was noticed, initially manifesting primarily as submucosal cellular infiltration, and mucosal erosion. Over the ensuing six weeks, the acute changes gave way to mucosal regeneration, and the appearance of granulation tissue in the submucosa. The stented segments remained patent, and feeding difficulties were limited to the immediate post-procedure period. These preliminary results suggest that peristaltic activity is no contraindication to the use of Z stents, though measures to limit the tissue response need to be identified.
Tablet buprenorphine hydrochloride when administered to 34 primigravida women sublingually in a dose of 6 micrograms/kg body weight during the first stage of labour, the analgesic action started 30 minutes after administration of drug and the analgesic action increased gradually and reached its peak level 3 hours after administration of drug. Analgesic action continued throughout the first stage of labour when the duration after administration of drug was 9 hours. In one case maximum analgesic action did not persist after 9 hours. The average time of delivery was 5.88 hours having cervical dilatation of 3.1 (+/- 0.13) cm and the progress of labour was not delayed by the drug. There was no cardiorespiratory depression of the subjects. None complained of nausea or vomiting. There was no change in foetal heart rate and Apgar scoring of neonates revealed the average value of 9.71 at 1 minute and 9.94 at 5 minutes.
Tissue factor, a 45-kilodalton membrane glycoprotein, is an essential cofactor for the plasma serine protease factor VII which activates factor X in the first step of the extrinsic coagulation cascade. Two adjacent lysine residues (numbers 165 and 166) were identified in the extracytoplasmic domain of tissue factor that are crucial for function. Site-directed mutagenesis of both lysines to alanines results in complete loss of activity. Mutation of either lysine alone results in a molecule which is much more sensitive to the phospholipid composition of the activating surface than the wild-type molecule. It is postulated that interactions between the extracytoplasmic domain of tissue factor and the membrane surface are necessary for bound factor VII or VIIa to assume a conformation capable of efficient catalysis.
We previously reported that morphine inhibits macrophage-colony stimulating factor (M-CSF)-induced proliferation of mouse bone marrow cells, both in vivo and in vitro, in a dose-dependent manner. We now report that either dynorphin A-(1-13) or dynorphin A-(1-10) amide, though having no effect on proliferation by themselves at concentrations less than 0.1 mM, can block the inhibitory effect of morphine both in vivo and in vitro, in a dose-dependent manner. The opioid antagonist naloxone can also block morphine's inhibitory effect on bone marrow cell proliferation in vivo, but has no effect in vitro. Dynorphin A-(1-13) was also able to block the dramatic reduction of spleen weight observed in animals chronically treated with morphine. Thus dynorphin, which has previously been shown to antagonize morphine analgesia, is also able to antagonize some of the immunosuppressive effects of morphine.
Interaction between Escherichia coli glutaminyl-tRNA synthetase (GlnRS) and its substrates have been studied by fluorescence quenching. In the absence of other substrates, glutamine, tRNA(Gln) and ATP bind with dissociation constants of 460, 0.22 and 180 microM, respectively. The presence of other substrates has either no effect or, at best a weak effect, on binding of ligands. Attempts to isolate enzyme-bound aminoacyl adenylate did not succeed. Binding of the phosphodiester, 5'-(methyl)adenosine monophosphate (MeAMP), to GlnRS was studied by fluorescence quenching and radioactive-ligand binding. tRNA also only has a weak effect on phosphodiester binding. Selectively pyrene-labeled GlnRS was used to obtain shape and size information for free GlnRS. A comparison with the GlnRS shape in the GlnRS/tRNA(Gln) crystal structure indicates that no major change in shape and size occurs upon tRNA(Gln) binding to GlnRS. 5,5'-Bis(8-anilino-1-naphthalene sulfonate) (bis-ANS), a non-covalent fluorescent probe, was also used to probe for conformational changes in GlnRS. This probe also indicated that no major conformational change occurs upon tRNA(Gln) binding. We conclude that lack of tRNA-independent pyrophosphate-exchange activity in this enzyme is not a result of either lack of glutamine or ATP binding in the absence of tRNA, or formation of aminoacyl adenylate and slow release of pyrophosphate. A conformational change is implied upon tRNA binding, which promotes pyrophosphate exchange. Fluorescence studies indicate that this conformational change must be limited and local in nature.
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Mouse thymocytes incubated in vitro with increasing concentrations of interleukin-1 (IL-1) in the presence of phytohemagglutinin (PHA) exhibited a dose-dependent increase in cell proliferation, as measured by [3H]thymidine incorporation. Under these conditions, there was a parallel dose-dependent increase in specific [3H]morphine binding, with a maximum increase of approximately 5-fold over basal levels. The binding sites differ from classical opioid receptors in that they are not stereo-selective. Interleukin-2 was ineffective in promoting either cell proliferation or enhanced opioid binding, but the effects of IL-1 could be mimicked by phorbol myristate acetate (PMA), suggesting the involvement of tyrosine phosphorylation. These results indicate that morphine-binding sites on immune cells can be regulated by cytokine activation.