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Biomedical subjects

S Roy

Publications and source records attributed to S Roy.

At least 631 records · Page 35Linked to original sources

Oligodendroglial tumors. An immunohistochemical and electron microscopic study.

Fifty-five cases of oligodendrogliomas and mixed oligoastrocytomas were evaluated using immunohistochemical (IH) study for glial fibrillary acidic protein (GFAP) and electron microscopic (EM) study. Most of the tumors in both of these groups showed many neoplastic oligodendroglial cells with GFAP-positive staining in their cytoplasm by IH study. By EM study too, many tumor cells showing features of oligodendroglial cells contained intermediate filaments. Our observations suggested the presence of a transitional form of cells in these tumors. The current study supports the contention that both oligodendrogliomas and oligoastrocytomas arise from a common progenitor cell capable of differentiation into both oligodendrocyte and astrocyte. The nature and degree of differentiation depends probably on gene expression and/or some microenvironmental factors.

Brain Neoplasms↗

Different molecular weight forms of opioid receptors revealed by polyclonal antibodies.

Polyclonal antibodies were raised against a purified opioid receptor from bovine brain (Cho, et. al., 1986), and shown to inhibit 3H-diprenorphine binding to this receptor in a dose-dependent fashion. These antibodies were then used to characterize opioid-binding material present in rat brain and in NG108-15 neuroblastoma-glioma hybrid cells. Western blot analysis revealed that the antibodies reacted with a single species of 58,000 molecular weight in rat brain membranes; this closely corresponds in size to the bovine opioid receptor used to raise the antibodies. In contrast, the polyclonal antibodies reacted with a 45,000 molecular weight species in NG108-15 neuroblastoma-glioma hybrid cells; moreover, this band was specifically reduced in NG108-15 cells in which opioid receptors had been down-regulated by incubation with D-ala2-D-leu5-enkephalin for 24 hours. Thus at least two distinct opioid receptor molecules have been identified, which have antigenic similarities.

Animals↗

Role of the mononuclear phagocyte system in the development of acquired immunodeficiency syndrome (AIDS).

This review describes current understanding of the role of cells of the mononuclear phagocyte system in the development of acquired immunodeficiency syndrome (AIDS). Monocyte-macrophage like cells have been shown to harbor human immunodeficiency virus type 1 (HIV-I) infection in both peripheral blood and bone marrow as well as in target organs such as brain, lungs, lymph nodes, and skin. Mononuclear phagocytes that have been infected by HIV-I do not undergo significant cytopathic changes, suggesting that they may be important viral reservoirs. These and related cells may also promote the slow, persistent nature of HIV-I infections by escaping host immunologic surveillance mechanisms. There is evidence that HIV-I infections in monocytes and premonocytes can initially be latent but progress to an active viral replication state upon differentiation and/or maturation. Functional abnormalities in the mononuclear phagocyte system following infection by HIV-I have also been described, and these may be partially responsible for the severe immunosuppression characteristic of AIDS and AIDS-related disorders. These defects may be mediated by quantitative and qualitative changes in the T-helper population. Although the role of mononuclear phagocytes as viral reservoirs and as mediators of immunosuppression is still largely speculative, increasing evidence suggests that these cells influence the course of HIV-I infections.

Acquired Immunodeficiency Syndrome↗

Isolation of DNA sequences on human chromosome 21 by application of a recombination-based assay to DNA from flow-sorted chromosomes.

By merging two efficient technologies, bivariate flow sorting of human metaphase chromosomes and a recombination-based assay for sequence complexity, we isolated 28 cloned DNA segments homologous to loci on human chromosome 21. Subregional mapping of these DNA segments with a somatic cell hybrid panel showed that 26 of the 28 cloned DNA sequences are distributed along the long arm of chromosome 21, while the other 2 hybridize with sequences on the short arm of both chromosome 21 and other chromosomes. This new collection of probes homologous to chromosome 21 should facilitate molecular analyses of trisomy 21 by providing DNA probes for the linkage map of chromosome 21, for studies of nondisjunction, for chromosome walking in clinically relevant subregions of chromosome 21, and for the isolation of genes on chromosome 21 following the screening of cDNA libraries.

Animals↗

Beneficial effect of second courses of cytotoxic therapy in children with minimal change nephrotic syndrome.

Therapeutic guidelines are not available for children with minimal change nephrotic syndrome (MCNS) who experience frequent relapses or develop steroid resistance after a course of cytotoxic therapy. The records of nine children with biopsy-proven MCNS who received two courses of cytotoxic therapy with either chlorambucil or cyclophosphamide were reviewed to evaluate the length of remission, associated side-effects and long-term outcome. Initial cytotoxic therapy was given to five frequent-relapsing patients and four steroid-resistant patients 2-48 months (mean 16 months) following diagnosis of nephrotic syndrome. The second drug was given 4-85 months (mean 27 months) after the first. Steroid-resistant patients attained remissions of 0-81 months (mean 23 months) following the first agent and 13-67 months (mean 32 months) following the second. Frequent-relapsing patients experienced remissions of 0.5-24 months (mean 7.4 months) following the first cytotoxic drug and 3-72 months (mean 22 months) after the second. Remissions following the second agent were equal to or longer than those following the first in the seven patients who received both chlorambucil and cyclophosphamide. In the 19- to 128-month follow-up (mean 66 months), all four steroid-resistant patients experienced infrequent relapses which responded to prednisone. One frequent-relapsing patient remains in remission, three have chronic proteinuria and one still has a frequent-relapsing course. For the select group of patients who become frequent relapsing or steroid resistant after one course of cytotoxic therapy, a second course of cytotoxic therapy may allow time for catch-up growth, as well as improve steroid responsiveness once relapses occur.

Adolescent↗

Evidence that smoking alters prostacyclin formation and platelet aggregation in women who use oral contraceptives.

Smoking markedly intensifies the risk of cardiovascular disease in women who use oral contraceptives. The mechanism of this effect is not known, but evidence in vitro and in male smokers suggests that nicotine and cigarette smoke can alter prostaglandin formation and platelet function. However, these effects had not been studied with regard to women. We evaluated the effects of smoking on prostacyclin formation and platelet aggregation in 38 women who were matched according to age and weight. These included 24 women who used oral contraceptives (15 smokers, 9 nonsmokers) and 7 smokers who did not use oral contraceptives. In addition, a control group comprised seven healthy, nonsmoking women who did not take oral contraceptives. Prostacyclin formation, reflected by the excretion rate of its stable metabolite 6-keto-prostaglandin F1 alpha, was measured by means of radioimmunoassay in 4-hour urine specimens obtained during a smoking-free period and after participants had inhaled smoke from four high-nicotine cigarettes. In addition, ex vivo platelet aggregation in response to adenosine diphosphate and the stable thromboxane/endoperoxide analog U 46619 was evaluated before and after the inhalation of cigarette smoke. Oral contraceptive users who smoked greater than or equal to 5 years had a lower basal 6-keto-prostaglandin F1 alpha level than nonsmokers or those with a smoking history of less than 5 years (84 +/- 11 versus 159 +/- 28 versus 171 +/- 18 ng/gm of creatinine, p less than 0.01). Inhalation of smoke from four high-nicotine cigarettes did not alter 6-keto-prostaglandin F1 alpha in the smokers who did not use oral contraceptives. However, excretion of 6-keto-prostaglandin F1 alpha was further reduced in the smokers who used oral contraceptives (133 +/- 20 to 86 +/- 9 ng/gm of creatinine, p less than 0.05). Platelet aggregation did not change after inhalation of cigarette smoke in the women who did not take oral contraceptives, but aggregation increased in participants who used oral contraceptives. These results suggest that prostacyclin inhibition may be an important mechanism for the increased cardiovascular risk in women smokers who take oral contraceptives.

6-Ketoprostaglandin F1 alpha↗

MMPI subtypes for chronic phencyclidine (PCP) abusers.

The present study applied empirical clustering procedures to the MMPI protocols of 196 chronic phencyclidine (PCP) abusers. Subjects were randomly divided into two groups, and two methods of cluster analysis, the average linkage method and Ward's hierarchical procedure, were performed. Both cluster methods produced highly comparable results within each group, and the MMPI profiles found in each group were quite similar. Cluster analytic studies of other substance abuse populations are needed in order to replicate the MMPI profile types found in the present study. These investigations would lead to an empirical typology across various substance abuse populations that would depict developmental stages.

Adult↗

High potency neuroleptics and violence in schizophrenics.

In a controlled study, inpatient violence was measured during placebo, high-potency (haloperidol) and low-potency (chlorpromazine or clozapine) neuroleptics. Some patients had a marked increase in violent behavior with the moderately high-dose haloperidol, but not with low-potency neuroleptics. The authors discuss reasons for the increased violence with haloperidol, including akathisia and drug-induced behavioral toxicity.

Adult↗

Increased expression of basement membrane components in human endothelial cells cultured in high glucose.

Although the degree of hyperglycemia is a powerful and independent risk factor for diabetic microvascular disease, it has not been established if and how high glucose per se can induce the typical lesions of microangiopathy. We have investigated in human vascular endothelial cells the expression of messenger RNA (mRNA) for collagen type IV and fibronectin, the two glycoproteins characteristically increased in diabetic basement membranes. In 12 confluent primary cultures exposed for 11 +/- 1 d (mean +/- SD) to 30 mM glucose and exhibiting cell number and thymidine incorporation similar to control cultures, the levels of collagen IV and fibronectin mRNA were, respectively, 238 +/- 140 and 221 +/- 231 percent of control (P less than 0.01). The effects of high glucose were selective (the levels of collagen I and c-myc mRNA remained unchanged), independent of the proliferative activity of the cultures and of the plating substratum, and maintained throughout multiple passages. However, several days of exposure to high glucose were required before their appearance. These observations establish that high glucose is a perturbation sufficient to mimic the effects of diabetes on the regulation of basement membrane components and propose that modifications in gene expression may pertain to the chain of events leading to diabetic angiopathy.

Basement Membrane↗

Past and present preferred prescribing practices of hormone replacement therapy among Los Angeles gynecologists: possible implications for public health.

Usual prescribing strategies of hormone replacement therapy for postmenopausal women by Los Angeles area gynecologists, both now and 10 years ago, were investigated by a mail survey. Of the 330 gynecologists who responded, estrogen therapy is currently used as a routine by nearly all (95 per cent), for women both with and without a uterus. Over three-fourths of these physicians favor use of 0.625 mg of conjugated equine estrogen. The estrogen is combined with cyclic progestin therapy, usually 10 mg of medroxyprogesterone acetate, by 86 per cent of gynecologists using estrogen for women with a uterus, and by 47 per cent for women without a uterus. Although conjugated equine estrogens were used widely for both groups of patients 10 years ago, a higher dose generally was preferred. Use of progestin therapy was uncommon (less than 20 per cent) for any postmenopausal patients at that time. Although the most common monthly therapeutic regimen for estrogen/progestin therapy is estrogen for days 1-25 and progestin for days 16-25, there is wide variation in prescribing strategies. We present these findings in the context of the probable effects of estrogen/progestin therapy on various chronic disease outcomes.

Adult↗

Imbalances in T cell subpopulations in human gliomas.

The quantitation of cells bearing CD3, CD4, CD8, and B cell phenotypic markers, as well as an estimation of serum immunoglobulin (Ig)G, IgA, and IgM, was carried out in a group of 39 glioma patients with different grades of malignancy. The findings were compared with those obtained from 21 normal healthy control subjects. The analysis revealed a significant decrease both in the absolute numbers and in the percentages of circulating CD3+ (p less than 0.001) and CD4+ (p less than 0.001) cells, while the CD8+ and Pan B+ cells remained within the normal range irrespective of the type and grade of tumor. The CD4+:CD8+ ratio was significantly decreased in all categories of patients. The CD4 lymphopenia was also evident in 10 patients who had no history of previous immunosuppressive drug therapy (steroids and anticonvulsants) until the commencement of the study. The Ig levels were within the normal range in patients with malignant astrocytoma and glioblastoma multiforme, whereas a three- and fourfold increase in the IgM level was observed in patients with astrocytoma. It is suggested that T cell lymphopenia in glioma patients could mainly be due to a selective depletion of CD4+ cells and that it occurs principally as a reaction to the tumor.

Adult↗

Identification of endogenous opioid receptor components in rat brain using a monoclonal antibody.

A monoclonal antibody generated against the tertiary structure of a partially purified opioid binding protein was used to probe the structure of the dynorphin and beta-endorphin receptors. The Fab fragment 3B4F11 inhibited completely the binding of 125I-beta-endorphin and [3H]dynorphin to rat brain P2 membranes with IC50 values of 26 ng/ml and 40 ng/ml, respectively. To explore further the interaction of 3B4F11 with the beta-endorphin receptor, the effect of the Fab fragment on 125I-beta-endorphin cross-linking to rat brain membranes was examined. 125I-beta-endorphin was covalently bound to three major species of approximate molecular weights 108,000, 73,000, and 49,000. The delta-selective ligand D-Pen2, D-pen5enkephalin was least effective at inhibiting the cross-linking of beta-endorphin, whereas the micro-selective ligand Tyr-D-Ala-Gly-NMe-Phe-Gly-ol and kappa-selective ligand U50488 inhibited beta-endorphin cross-linking to the 108,000 and 73,000 Da species. Both 3B4F11 and beta-endorphin prevented the covalent binding of 125I-beta-endorphin to all three labeled species. These findings suggest that micro and kappa receptor types might have some structural similarities, whereas the delta receptor type might differ in molecular size. In addition, the micro, kappa, and delta ligands might have different primary sequences, whereas their tertiary structures might share regions of molecular homology with all three receptor constituents labeled by 125I-beta-endorphin. 3B4F11 will be a valuable tool for the purification and isolation of the several components of the beta-endorphin receptor complex.

Animals↗

Digital subtraction angiography in the evaluation of renal vascular hypertension in children.

Twenty children were evaluated with digital subtraction angiography (DSA) for renal vascular hypertension. IV DSA from a basilic vein approach was performed in four patients and femoral vein approach in two patients. Intraarterial DSA was performed in 14 patients with suspected renal vascular hypertension. Renal vein renin samples were obtained from 17 patients. Two renal artery angioplasties were performed in association with intraarterial DSA. IV DSA was diagnostic in five of six patients with one false-negative result for fibromuscular dysplasia of the tertiary vessels. Intraarterial DSA images were diagnostic in 14 of 14 patients, and renal vein renin results correlated well with DSA results. In 11 patients, DSA was performed as an outpatient (hospital day-care unit) procedure. Of the 20 patients evaluated, 13 patients had abnormal DSA findings which included a hypoplastic but functioning kidney in three patients, distal small vessel abnormalities in five patients, unilateral or peripheral renal artery stenosis in four patients, and middle aortic syndrome in one patient. DSA with renal vein renin samples can be used as a diagnostic procedure for the evaluation of renal vascular hypertension in children as well as adult patients. In addition, it is a useful tool for therapeutic vascular procedures in children.

Adolescent↗