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S Roy

Publications and source records attributed to S Roy.

At least 559 records · Page 31Linked to original sources
PubMed1991

Expression of genes related to the extracellular matrix in human endothelial cells. Differential modulation by elevated glucose concentrations, phorbol esters, and cAMP.

To identify agents and mechanisms responsible for the thickened basement membranes characteristic of diabetic angiopathy we examined the effects of high glucose (30 mM) on the expression of genes related to extracellular matrix composition and turnover and investigated whether the changes induced by high glucose were mimicked and sustained by activation of protein kinase C or A. In human umbilical vein endothelial cells high glucose increased fibronectin, collagen IV, tissue plasminogen activator (tPA), and plasminogen activator-inhibitor 1 (PAI-1) mRNA levels 2-fold but did not affect type IV and interstitial collagenase expression. Acute treatment with phorbol esters resulted in increased collagen IV, tPA, PAI-1, and interstitial collagenase mRNAs; the type IV collagenase mRNA levels were instead suppressed to 50% of control. Upon longer exposure to phorbol esters (48 h) suppression of fibronectin and PAI-1 mRNAs also occurred. Intracellular elevation of cAMP led to over-expression of fibronectin and type IV collagenase and potentiated the effects of phorbol esters on collagen IV, tPA, and interstitial collagenase expression. The mRNA changes induced by high glucose occurred in the absence of protein kinase C activation or cAMP elevation. These studies indicate that events other than activation of protein kinase C or A bridge high ambient glucose to changes in endothelial cell gene expression that may contribute to diabetic angiopathy.

1-Methyl-3-isobutylxanthine↗
PubMed1991

The number of positively charged amino acids in the basic domain of Tat is critical for trans-activation and complex formation with TAR RNA.

The basic domain of Tat is required for trans-activation of viral gene expression. We have performed scanning peptide studies to demonstrate that only this domain is capable of binding to the TAR RNA stem-loop. Strikingly, the basic domain of the other human immunodeficiency virus trans-acting factor, Rev, but no other region, is also capable of binding to TAR. Peptide derivatives of Tat do not require the highly conserved glutamine residue at position 54 for TAR binding, since it may be substituted or deleted. In addition, the two lysine residues may be replaced by arginines. Analysis of binding and trans-activation demonstrated that homopolymers of arginine can completely substitute for the basic domain. Such homopolymers have high affinity for wild-type TAR RNA and lower affinity for mutant TAR. Homopolymers of six to nine arginines substituting for the basic domain of Tat enable full trans-activation in vivo. Homopolymers of at least seven arginines are required for detectable in vitro complex formation, although approximately 30% trans-activation is achieved with a mutant Tat containing only five arginines.

Amino Acid Sequence↗
PubMed1991

Karyotype studies of patients with gonadal tumors.

Chromosomes from the peripheral blood of 10 patients with gonadal tumors were studied to detect any inherent chromosomal defect. Aneuploidy, breakages and loss of chromosome X were observed. In all cases the karyotype was compatible with the phenotype.

Adenocarcinoma, Mucinous↗
PubMed1991

Chronic morphine treatment selectively suppresses macrophage colony formation in bone marrow.

Opioids have been shown to have diverse effects on the immune system, both in vivo and in vitro, but their interactions on immature progenitor cells have been little studied. We have examined the effects of chronic morphine treatment of mice on colony formation by bone marrow cells in vitro. Bone marrow cells from mice implanted with morphine pellets for 72 h showed a 65% decrease in their response to macrophage colony stimulating factor (M-CSF). In contrast, chronic morphine treatment had no effect on the response of bone marrow cells to granulocyte/macrophage colony stimulating factor (GM-CSF). Removal of the morphine pellets from the mice resulted in a time-dependent reversal of the inhibition of macrophage colony formation, and the inhibition was completely blocked by simultaneous administration of naloxone and morphine pellets to the mice. No inhibition of colony formation was observed in bone marrow cells from mice treated with a single acute dose of morphine. Incubation of bone marrow cells from untreated mice for 7 days with in vitro morphine concentrations as low as 25 microM also reduced macrophage colony formation, and the opioid peptide beta-endorphin was even more potent, significantly reducing macrophage colony formation at concentrations as low as 0.25 microM. In agreement with the in vivo effects, neither opioid in vitro had a significant effect on granulocyte/macrophage colony formation. These results suggest that opioids may significantly alter the maturation of immune cells, which could result in potent effects on overall immune competence.

Animals↗
PubMed1991

Self-association of tissue factor as revealed by chemical crosslinking.

The possible self-association of tissue factor molecules was investigated by treating cells expressing tissue factor with bifunctional cross-linking agents. The two reagents chosen were 3,3'-dithiobis(sulfosuccinimidylpropionate) and sulfosuccinimidyl 2-(p-azidosalicylamido)ethyl-1,3'-dithiopropionate, both of which are membrane-impermeable and thiol-cleavable. A human bladder carcinoma cell line, J82, and a transfected human kidney cell line expressing high amounts of recombinant tissue factor were used in these studies. Exposure of the intact cells to the crosslinking reagents was found to result in the formation of multimeric tissue factor-containing complexes, the extent of which appeared to be dependent upon the amount of tissue factor expressed by the cell. The self-association of tissue factor was prevented in a variant tissue factor molecule harboring a non-homologous transmembrane domain.

Amino Acid Sequence↗
PubMed1991

Immunobiological studies on experimental visceral leishmaniasis. I. Changes in lymphoid organs and their possible role in pathogenesis.

Studies were carried out to determine changes in lymphoid organs i.e. spleen, lymph node and bone marrow (BM) in progressive experimental visceral leishmaniasis. Mononuclear phagocytes in the BM were increased; spleens showed a hypercellularity coupled with a rise in parasite burden while secondary follicles with no apparent depletion of paracortex were seen in the lymph node. This enhanced proliferation of mononuclear phagocytes in the BM and probably their subsequent recruitment in the spleen could be induced in naive recipients by injecting nylon wool-purified lymph node cells derived from infected mice together with sonicated leishmanial antigen(s). Similar changes could also be induced in the BM of naive recipients by injecting serum of infected mice. In control experiments where both donor and recipients were uninfected such changes were not apparent. A working hypothesis is proposed to delineate the role of lymphoid organs in the pathogenesis of experimental visceral leishmaniasis.

Animals↗
PubMed1991

Fibrosarcoma of the scalp following postoperative radiotherapy for medulloblastoma.

A rare case of fibrosarcoma of the scalp following postoperative radiotherapy for medulloblastoma is reported. A review of similar cases in the literature was undertaken in an attempt to find a correlation between the dose of radiation, the length of the latent period, and the nature of the neoplasm. A significantly shorter latent period was found for sarcomas. No relationship was observed between the radiation dose and the latent period. The present case is unique in that the post-irradiation neoplasm (PIN) occurred in a predominantly extracranial site after treatment for a desmoplastic medullobastoma and had a remarkably short latent period.

Cerebellar Neoplasms↗
PubMed1991

Nonbarrier contraceptives and vaginitis and vaginosis.

Within the limitations of the available data, it has been reported that oral contraceptive use versus other contraceptive methods is associated with a greater or similar frequency of candidiasis, increased numbers of anaerobic microorganisms, an increased or similar frequency of chlamydia trachomatis, and a reduced frequency of bacterial vaginosis and trichomoniasis. The impact of contraceptive steroids on cellular and humoral immunologic factors may explain these observations. Intrauterine contraceptive device use is reported to be associated with an increased rate of bacterial vaginosis and anaerobic organism recovery from the vagina regardless of symptoms. Patients having a contraceptive vaginal ring were found to have the same number and types of vaginal organisms as oral contraceptive users. Levonorgestrel-releasing subdermal implant (Norplant, Wyeth-Ayerst, Philadelphia, Pa.) users have been reported to have approximately half the rate of vaginitis and vaginosis compared with that of Copper T-200 intrauterine device users.

Candidiasis, Vulvovaginal↗
PubMed1991

Plasma terminal complement complexes in acute poststreptococcal glomerulonephritis.

In most instances of acute poststreptococcal glomerulonephritis (APSGN), activation of the complement system occurs, as reflected by decreased levels of the complement proteins C3, C5, and properdin (P). Recent studies implicate terminal complement complexes (TCC) in the pathogenesis of glomerular injury. The fluid phase TCC, SC5b-9, reflects the formation of membrane-bound C5b-9 and has been used as a clinical marker in various diseases. Plasma concentrations of SC5b-9 were measured with an enzyme immunoassay using a monoclonal antibody to a neoantigen expressed on the SC5b-9 complex in 13 children who presented with clinical and pathologic features of APSGN. SC5b-9 was significantly elevated in all plasmas obtained within 30 days after onset of clinical glomerulonephritis. Concentrations of SC5b-9 in acute plasmas were significantly higher than those of paired convalescent samples. For individual patients, as SC5b-9 concentration returned to normal there was a coincident decrease in serum creatinine concentration and urinary protein excretion, signifying clinical improvement in glomerulonephritis. Thus, TCC generation commonly occurs in the early stages of APSGN and may be of importance in the pathogenesis of the condition.

Antigen-Antibody Complex↗
PubMed1991

Clinical and immunopathological results of a phase II study of perilymphatically injected recombinant interleukin-2 in locally far advanced, nonpretreated head and neck squamous cell carcinoma.

Fifteen patients with locally far advanced, nonpretreated head and neck squamous cell carcinoma were treated with low-dose recombinant interleukin-2, using 10 daily perilymphatic injections. The therapy was well tolerated. No tumor regression was observed. Tumor biopsies were taken before and after treatment. Histopathological studies including evaluation of the mononuclear cell infiltrate and immunohistochemical detection of human leukocyte antigen (HLA) expression on tumor cells were performed. HLA class I was not detectable in 1 of 10 samples, and HLA class II expression was seen in 2 of 10 samples. As compared to pretreatment biopsies, no changes were found after treatment. This is in agreement with the lack of a clinical response.

Adult↗
PubMed1991

Critical chemical features in trans-acting-responsive RNA are required for interaction with human immunodeficiency virus type 1 Tat protein.

The human immunodeficiency virus type 1 Tat protein binds to an RNA stem-loop structure called TAR which is present at the 5' end of all human immunodeficiency virus type 1 transcripts. This binding is centered on a bulge within the stem of TAR and is an essential step in the trans-activation process which results in a dramatic increase in viral gene expression. By analysis of a series of TAR derivatives produced by transcription or direct chemical synthesis, we determined the structural and chemical requirements for Tat binding. Tat binds well to structures which have a bulge of two to at least five unpaired bases bounded on both sides by a double-stranded RNA stem. This apparent flexibility in bulge size is in contrast to an absolute requirement for an unpaired uridine (U) in the 5'-most position of the bulge (+23). Substitution of the U with either natural bases or chemical analogs demonstrated that the imido group at the N-3 position and, possibly, the carbonyl group at the C-4 position of U are critical for Tat binding. Cytosine (C), which differs from U at only these positions, is not an acceptable substitute. Furthermore, methylation at N-3 abolishes binding. While methylation of U at the C-5 position has little effect on binding, fluorination reduces it, possibly because of its effects on relative tautomer stability at the N-3 and C-4 positions. Thus, we have identified key moieties in the U residue that are of importance for the binding of Tat to TAR RNA. We hypothesize that the invariant U is involved in hydrogen bond interactions with either another part of TAR or the TAR-binding domain in Tat.

Base Composition↗
PubMed1991

The integrity of the stem structure of human immunodeficiency virus type 1 Tat-responsive sequence of RNA is required for interaction with the interferon-induced 68,000-Mr protein kinase.

A number of eucaryotic viruses have devised strategies to minimize the deleterious effects on protein synthesis caused by activation of the interferon-induced, double-stranded-RNA-activated protein kinase, P68. In a recent report, we described the down regulation of the P68 protein kinase in cells infected by human immunodeficiency virus type 1 (HIV-1) (S. Roy, M. G. Katze, N. T. Parkin, I. Edery, A. G. Hovanessian, and N. Sonenberg, Science 247:1216-1219, (1990). We now present evidence that such a decrease in amounts of P68 could be essential for HIV-1 replication because of the presence of the Tat-responsive sequence (TAR sequence) present in the 5' untranslated region of HIV-1 mRNAs, which activates the P68 kinase. We found that poly(A)+ mRNAs prepared from HIV-1-infected cells efficiently activated the protein kinase as did mRNAs from stably transformed cell lines constitutively expressing the TAR region. Furthermore, we found that TAR-containing RNAs complexed with purified P68 protein kinase in vitro by two independent assays and could be cross-linked to P68 kinase present in a HeLa cell extract. Experiments using in vitro-synthesized wild-type and mutant TAR RNAs revealed that both the efficient binding to and the activation of P68 kinase were dependent on the TAR RNA stem structure. The TAR-P68 complex could be competed out by a synthetic RNA that bound to and activated the protein kinase but not by a synthetic RNA that bound with low affinity and did not activate P68. The possible biological consequences of a P68-TAR interaction that may include the switch from latent to active virus replication are discussed.

Base Sequence↗
PubMed1991

High prevalence of systemic disease and mortality in Asian subjects with systemic lupus erythematosus.

All patients with systemic lupus erythematosus (SLE) (American Rheumatism Association criteria with positive antinuclear antibody titre) and who attended any of the three general hospitals in Leicester over a 10 year period were ascertained using several complementary sources. Eighty seven subjects (26 Asian, 61 white) were identified. The estimated prevalence of SLE in Leicester is 0.4/1000 for Asian and 0.2/1000 for white subjects. Mean age of onset of the disease was 24 years in Asian and 31 years in white subjects, with both groups showing a female preponderance. Proteinuria (greater than 1 g/24 h) was noted in 15 (58%) Asian and 21 (35%) white subjects; neuropsychiatric disease in 10 (38%) Asian and 8 (13%) white subjects; myalgic symptoms with raised muscle enzymes in 9 (35%) Asian and 3 (5%) white subjects. Nineteen (73%) Asian subjects were positive for extractable nuclear antigens as well, at some stage of their disease, compared with 6 (10%) white subjects. Immunosuppressive treatment was required in 12 (46%) Asian and 12 (20%) white subjects, and deaths of seven Asian and five white subjects were attributed to SLE. These findings show that Asian subjects have a higher prevalence of SLE with greater systemic disease and mortality.

Adult↗
PubMed1991

Prevalence of tardive dyskinesia among three ethnic groups of chronic psychiatric patients.

The relationship between prevalence of tardive dyskinesia and ethnicity (black, white, or Hispanic) was examined in a group of 491 chronic psychiatric patients at a large state psychiatric hospital in California. Overall, the prevalence of tardive dyskinesia was 17.7 percent. No significant differences in the prevalence of tardive dyskinesia or in neuroleptic dosage levels were found among the three groups. A relationship was found between lower prevalence of tardive dyskinesia and higher current neuroleptic dosage, suggesting that higher dosage masks symptoms of tardive dyskinesia.

Adult↗
PubMed1991

Characteristics and mechanisms of high-glucose-induced overexpression of basement membrane components in cultured human endothelial cells.

Growing evidence that high glucose may be a causative agent of the thickened vascular basement membranes that characterize diabetic microangiopathy prompted this investigation of the underlying mechanisms. When exposed to 30 mM glucose, 70% of 52 primary cultures of human endothelial cells, each derived from a single umbilical vein, showed increased levels of fibronectin (median 181% of control, range 104-549%) and collagen IV mRNA (175% of control, range 101-807%). The response of the two transcripts to high glucose was concordant in 77% of the 52 cultures studied (P = 0.01), required 5 days of exposure, and was accompanied by proportionally increased synthesis of the respective protein. Laminin B1 expression was also upregulated by high glucose, concordantly with that of fibronectin and collagen IV. Increased fibronectin and collagen IV mRNA levels resulted from increased gene transcription (median 183 and 236% of control, respectively) without evidence of translational regulation, were not triggered by hypertonicity or signals originating from the matrix, and were also induced by hexoses with limited (D-galactose) or no (L-glucose) access to metabolic pathways but capable of inducing nonenzymatic glycosylation. There was no amplification of the overexpressed genes. Thus, high glucose upregulates in a coordinated fashion the transcription of genes coding for basement membrane components through effects exerted intracellularly or at the cell-matrix boundary and modulated by individual characteristics of the target cells.

Basement Membrane↗