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Biomedical subjects

S Roy

Publications and source records attributed to S Roy.

At least 595 records · Page 33Linked to original sources
PubMed1990

Overexpression of fibronectin induced by diabetes or high glucose: phenomenon with a memory.

To identify events and mechanisms that might contribute to the poor reversibility of diabetic complications, we examined whether diabetes or high glucose induces changes in gene expression and whether such changes outlast the presence of the metabolic abnormalities. The study focused on fibronectin because the increased amounts of this glycoprotein found in diabetic tissues and thickened basement membranes are as yet unexplained. In streptozotocin-induced diabetic rats, fibronectin mRNA levels were increased to 304 +/- 295% of control (mean +/- SD) in the kidney cortex (P less than 0.02), and to 271 +/- 273% of control in the heart (P less than 0.02), while actin mRNA levels remained unchanged. Elevation of fibronectin mRNA persisted for weeks after restoration of near-normoglycemia. In cultured human endothelial cells, high glucose-induced overexpression of fibronectin and collagen IV remained detectable after replating and multiple cell divisions in the absence of high glucose. Cells shifted to normal-glucose medium after prolonged exposure to high glucose also exhibited a proliferative advantage over cells chronically maintained in normal glucose. Thus, diabetes increases fibronectin expression in tissues that are known targets of the complications, and the effect is not readily reversible. The in vitro studies suggest that hyperglycemia may be responsible for these events through induction of self-perpetuating changes in gene expression.

Animals↗
PubMed1990

A bulge structure in HIV-1 TAR RNA is required for Tat binding and Tat-mediated trans-activation.

The Tat protein of human immunodeficiency virus type 1 (HIV-1) trans-activates viral gene expression and is obligatory for virus replication. Tat function is mediated through a sequence termed TAR that comprises part of the 5'-noncoding region of all HIV-1 mRNAs. This region forms a stable stem-loop structure in vitro. Recent evidence indicates that Tat binds directly to the TAR RNA sequence, and this binding is independent of the nucleotide sequence in the loop but dependent on the integrity of the upper stem. We used the electrophoretic mobility-shift assay to identify the sequence and structure specificity of this interaction and its correlation with Tat trans-activation. We show that a 3-nucleotide bulge structure (positions +23 to +25) in TAR RNA is important for both Tat interaction with TAR RNA and Tat-mediated trans-activation of gene expression. Single base substitutions at position +23 that impair Tat-mediated trans-activation in vivo also reduce binding of Tat to TAR in vitro, suggesting that the first uridine residue in the bulge is the critical base for both functions. In contrast, mutations in the loop (positions +31 to +34) and the stem (positions +9 to +12 and +49 to +52), which reduce Tat-mediated trans-activation, had no effect on Tat binding. We also show that a Tat peptide that includes the basic region required for nucleolar localization binds to TAR RNA with the same specificity as the full-length protein. We conclude that Tat binding to TAR is necessary but not sufficient by itself to account for trans-activation.

Base Sequence↗
PubMed1990

A method for extracorporeal heparin removal from blood by affinity chromatography.

A high level of heparin, infused into blood, often causes severe complications such as hemorrhage, especially when a drug is administered over a long period. The most common way of preventing a patient from bleeding after transfusion is by administering a heparin antagonist such as protamine. The complex molecules formed between heparin and protamine, if left in the bloodstream, may cause hypotension and other side effects. Protamine was immobilized as a bioligand on the affinity matrix formed by grafting an acrylic polymer on cellulose backbone. By flowing blood tangentially along the matrix surface immobilized with protamine, 70-90% heparin reduction was achieved from 1 L of blood containing 10 IU/ml of heparin studied in vitro. The acrylic gel surface avoids lysis of blood, the cellulose support sustains the flow of viscous blood at 50 ml/min, and the tangential flow design permits direct processing of blood without pressure buildup in the system. The example demonstrates the feasibility of applying such a device as a means of immunoadsorptive filter for the selective removal of disease-causing factors from blood.

Chromatography, Affinity↗
PubMed1990

Structural requirements for trans activation of human immunodeficiency virus type 1 long terminal repeat-directed gene expression by tat: importance of base pairing, loop sequence, and bulges in the tat-responsive sequence.

In order to elucidate the molecular mechanisms of action of the tat-responsive sequence, mutational analysis of the tat-responsive sequence was carried out. The most critical region comprised nucleotides +18 to +44 and included the 3-nucleotide bulge at positions +23 to +25, the loop sequence, and an intact stem. In addition, base pairing up to nucleotide +52 was required for the full magnitude of the trans-activation response. Single-nucleotide bulges at positions +5 to +17 were dispensable. Analysis of truncated and full-length transcripts demonstrated that a transcriptional antitermination model does not fully account for trans activation.

Base Composition↗
PubMed1990

Benign nerve sheath tumors: a light microscopic, electron microscopic and immunohistochemical study of 102 cases.

One hundred and two cases of benign nerve sheath tumors (NSTs) were studied with a combined approach using routine light microscopy (LM), immunohistochemistry (IH) for myelin basic protein (MBP) and S-100 protein as well as transmission electron microscopy (TEM) with the aim of obtaining greater insight into the true nature of these neoplasms, and also to establish the importance of IH and TEM in their diagnosis. Myelin basic protein was not identified in any of these tumors, whereas S-100 protein was positive to a variable degree in both schwannomas and neurofibromas. TEM revealed that Schwann cells predominated in tumors which were strongly positive for S-100 protein and appeared as schwannomas by LM. However, neurofibromas showing a variable patchy positivity for S-100 were composed of an admixture of Schwann cells, fibroblast-like cells and intermediate cells considered to be modified Schwann cells. Perineurial cells in typical form were not seen. It is concluded that all NSTs are basically of Schwann cell origin and that the intermediate cells and fibroblast-like cells are variants of Schwann cells. The different morphological appearances and biological behaviour of schwannomas and neurofibromas may be related to some other factors like micro-environment or genetic predisposition. Further, both IH, especially for S-100 protein, and TEM play an important role in establishing their diagnosis.

Cranial Nerve Neoplasms↗
PubMed1990

Persistent immune complexes and abnormal CD4/CD8 ratios in HIV infection.

We assessed the immunopathologic role of circulating immune complexes in human immunodeficiency virus infection by evaluating the data base and the serum bank of the San Francisco Men's Health Study, a longitudinal clinical and epidemiological investigation conducted since 1983. A group of 4,276 sera from 1,023 (including 811 homosexual/bisexual) men were tested for circulating immune complexes. We used a modification of the commercially available enzyme immunoassay test, based on monoclonal anti-C1q antibodies coupled to the solid phase, for capturing circulating immune complexes from the test serum, followed by detection of circulating immune complexes with either anti-IgG or with anti-IgM probes. Although persistent IgM and IgG circulating immune complexes were most frequently encountered in human immunodeficiency virus-seropositive homosexual/bisexual men, they were not an indicator of disease progression as assessed by abnormalities in the absolute numbers or ratios of CD4- and CD8-positive T cells, or clinical signs and symptoms of AIDS/ARC.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Xanthomatous change in tumours of glial origin.

Six patients with glial tumours showing xanthomatous change are reported here. Four patients in the series showed features of anaplastic (malignant) glioma or glioblastoma multiforme. In these patients, the astrocytic origin of the xanthomatous cells was confirmed by electron microscopy and immunohistochemistry using glial fibrillary acidic protein (GFAP). Of these, in one patient (no. 4) xanthomatous change was seen in an anaplastic (malignant) mixed glioma with significant ependymal component. Only one patient (no. 5) could be considered histologically as pleomorphic xanthoastrocytoma, but no clinical follow up was available. The value of immunohistochemical staining for GFAP in distinguishing gliomas with xanthomatous change from true xanthofibromas and xanthosarcomas was demonstrated in one patient (no. 6) in whom the glioblastomatous areas were GFAP positive but the xanthomatous areas were negative. This was therefore considered as a rare condition of glioblastoma with xanthosarcoma.

Astrocytoma↗
PubMed1990

A comparison of the efficacy and safety of ceftizoxime with doxycycline versus conventional CDC therapies in the treatment of upper genital tract infection with or without a mass.

It is well known that sexually transmitted infections of the upper genital tract are widespread. A variety of regimens are used to treat these conditions, many of which have not been subjected to randomized, prospective clinical trials (including the 1985 Centers for Disease Control [CDC] Guidelines for the treatment of upper genital tract infections [UGTI]). This investigation was undertaken to compare the 1985 CDC treatment guidelines with different doses of ceftizoxime, a third-generation cephalosporin with an intermediate half-life, plus doxycycline in patients with UGTI. The patients were divided into subgroups, depending on the presence or absence of a pelvic mass. Sixty-seven women participated in the study. They were older than 14 years of age and required hospitalization for the treatment of UGTI. These women had lower abdominal pain and tenderness, cervical motion or adnexal tenderness, and one of the following: temperature greater than 100.4 degrees F orally, leukocytosis greater than 10,500/mm3, or presence of a suspected inflammatory pelvic mass on pelvic examination or by ultrasound. Informed consent was obtained from all patients in a manner approved by the Institutional Review Board. Pelvic examinations and ultrasound evaluations of the pelvic soft tissues were performed on all patients at the time of admission. Those who were found not to have a pelvic mass or who had a pelvic mass less than 4 cm in transverse diameter were randomly allocated to receive either ceftizoxime 2 gm intravenously every 12 hours with doxycycline 100 mg intravenously twice daily (Rx 1, n = 13) or cefoxitin 2 gm intravenously every six hours with doxycycline 100 mg intravenously twice daily (Rx 2, n = 14). Those patients found to have a pelvic mass (greater than 4 cm in transverse diameter) were randomly allocated to receive either ceftizoxime 2 gm intravenously every eight hours with doxycycline 100 mg intravenously twice daily (Rx 3, n = 19) or clindamycin 900 mg intravenously every eight hours with a 2-mg/kg loading dose of gentamicin followed by 1.5 mg/kg intravenously every eight hours, with adjustments as necessary (Rx 4, n = 21). All UGTI patients without a mass treated with either Rx 1 or Rx 2 responded adequately. However, UGTI patients with a mass treated with Rx 4 were more likely than those treated with Rx 3 to require a change in antibiotics or need extirpative surgery in order to obtain a satisfactory clinical response (Fisher's exact test = 0.046, two-sided).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Self-injury in psychiatric in-patients.

Suicide and self-injury in-patients were identified on the basis of a retrospective content analysis of special incidence reports completed the preceding year at an urban state psychiatric hospital. Select clinical and biodemographic variables were then examined, and in order to determine the importance of these variables in the prediction of incident severity, a multiple regression analysis was performed. Schizophrenic patients were found to be significantly over-represented among both the self-injury and suicide patients.

California↗
PubMed1990

A clinico-pathologic study of pituitary adenomas.

One hundred patients of pituitary adenoma were studied using light microscopy, electron microscopy, immunohistochemistry and serum hormone estimation. Depending on the absence or presence of clinical endocrine manifestation they were divided into 2 groups 'non-functioning' (group I -48 patients) and 'hyper-functioning' (group II- 52 patients). Tumours in group I were chromophobes, some of which (group IA) had no hormone increase in serum nor detection in tissues and ultrastructurally they consisted of secretorily inactive cells (null cell adenomas) while others (group IB) were composed of secretorily active cells with prolactin consistently increased in serum and localized in tissue (lactotroph adenomas). Tumours in group II were chromophobe, acidophil, basophil or mixed adenomas with varying number of secretorily active cells in all. The hormone responsible for the hyperfunction was always raised in serum and localized in tissue. Thus growth hormone was demonstrated in all tumours from patients with acromegaly (somatotroph adenomas), prolactin in all tumours from patients with galactorrhea (lactotroph adenomas) and ACTH in all tumours from patients with Cushing's syndrome (corticotroph adenomas). It was observed, however, that 40 per cent of tumours were pleurihormonal, growth hormone and prolactin being the commonest combination. Interestingly, not all the hormones localized by immunohistochemistry in pleurihormonal adenomas were detected in serum and/or reflected in the clinical picture.

Adenoma↗
PubMed1990

Cefmetazole and cefonicid. Comparative efficacy and safety in preventing postoperative infections after vaginal and abdominal hysterectomy.

A single 1-g dose of cefmetazole was compared with a single 1-g dose of cefonicid for prophylaxis in vaginal and abdominal hysterectomy to determine their efficacy and safety. The antibiotics were administered intramuscularly 15-90 minutes before the incision was made. Cefmetazole and cefonicid had similar activity against most of the aerobic organisms recovered, but cefmetazole was significantly more active against anaerobic gram-negative microorganisms. The patterns of regrowth of vaginal flora were similar in the two treatment groups. Patient demographic characteristics and surgical procedures were similar in both groups. The difference in primary prophylactic failure (e.g., cuff cellulitis) with the two study drugs (1 of 53 [1.9%] with cefmetazole and 2 of 28 [7.1%] with cefonicid) did not reach statistical significance, and the results were similar for the two routes of hysterectomy. Cefmetazole, at a dose of 1 g intramuscularly preoperatively, is a safe and effective agent for prophylaxis during hysterectomy.

Adult↗
PubMed1990

Pentoxifylline, a methylxanthine derivative, prevents postsurgical adhesion reformation in rabbits.

Previous studies from our laboratory have demonstrated pentoxifylline to be a potent inhibitor of primary post-traumatic adhesion formation in a rodent model. To evaluate pentoxifylline in a situation more closely mimicking the events encountered in infertility surgery, we developed a model for adhesion reformation after lysis of pelvic adhesions. New Zealand White rabbits received a standardized primary traumatic lesion to the left uterine horn. One week later, a laparotomy was performed for evaluation (prescore) and subsequent lysis of adhesions. After closure, the animals were randomized to treatment with vehicle or subcutaneous pentoxifylline, 2.5 mg/kg, administered at 12-hour intervals for six doses. Seven days later, the rabbits were sacrificed and evaluated in a blinded manner to quantify adhesion reformation (postscore). Using a scoring scale from 0 = no adhesions to 4+ = most severe, the mean prescore was not different between pentoxifylline-treated and control rabbits (3.8 versus 3.9, respectively). However, the mean postscore (0.7 versus 3.7, respectively) was markedly reduced by pentoxifylline (P less than .001). These data demonstrate a marked inhibition of adhesion reformation after lysis of pelvic adhesions under the influence of pentoxifylline in rabbits.

Animals↗