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Biomedical subjects

S Roy

Publications and source records attributed to S Roy.

At least 343 records · Page 19Linked to original sources
PubMed1997

Proliferative effect of high glucose is modulated by antisense oligonucleotides against fibronectin in rat endothelial cells.

Increased synthesis of fibronectin is associated with the development of basement membrane thickening-a characteristic lesion of diabetic microangiopathy, and it may affect the function of vascular cells. Because antisense technology offers the possibility to modulate specific gene expression, we investigated the effect of antisense phosphorothioate oligonucleotides directed against fibronectin mRNA on fibronectin synthesis and cell proliferation in a cell line derived from rat microvascular endothelium and cultured under high (30 mmol/l) glucose conditions. The rat endothelial cells grown in high glucose medium for 5.6 +/- 1.3 days exhibited increased cell proliferation compared to control cells grown in 5 mmol/l glucose (149% of control, p = 0.006). Fibronectin protein and mRNA levels (determined by Western blotting and reverse transcription-polymerase chain reaction) were also increased to 157%, p = 0.012 and 178%, p = 0.034 of control, respectively. However, when cells grown in high glucose medium were transfected with 0.4 mmol/l fibronectin-antisense phosphorothioate oligonucleotides in the presence of cationic liposomes, the cell number, fibronectin protein, and mRNA levels decreased compared to untransfected cells grown in high glucose medium to 102, 69, and 107% of control, respectively. This study shows that fibronectin antisense oligonucleotides targeted to the translation initiation site of the fibronectin transcript specifically reduce fibronectin synthesis in rat endothelial cells and the proliferative effect of high glucose concentrations.

Animals↗
PubMed1997

Autosomal recessive polycystic kidney disease: long-term outcome of neonatal survivors.

Autosomal recessive polycystic kidney disease causes renal and hepatic dysfunction in childhood. We describe the clinical outcome of 52 children with this diagnosis born between 1950 and 1993. Currently 23 are alive, 24 dead and 5 have been lost to follow-up; 1 has been dialysed and 7 transplanted. Life-table analysis of the patients surviving the 1st month of life revealed an actuarial renal survival of 86% at 1 year and 67% at 15 years. The probability of requiring anti-hypertensive treatment was 39% at 1 year and 60% at 15 years of age. Bleeding from gastro-oesophageal varices occurred in 8 patients at a mean age of 12.5 years, and was preceded by haematological evidence of hypersplenism in 6 of them. The study indicates a relatively good prognosis for patients with this condition who survive the neonatal period and emphasises the importance of early detection and appropriate management of systemic and portal hypertension.

Adolescent↗
PubMed1997

Increased recognition of IgA nephropathy in African-American children.

Based upon the percentage of cases of IgA nephropathy (IgAN) in biopsy series, a lower prevalence has been assumed for African-Americans compared with Americans of European descent. This may be due to a racial difference in the basic underlying pathology of IgAN or to racial differences in patterns of referral and biopsy selection practices. Over the past decade (1985-1994), we have found similar incidences of IgAN in Caucasian and African-American children from Shelby County, Tennessee. The incidence was 3.0 cases per million per year for Caucasian and 5.7 cases per million per year for African-American children. IgAN may be more common in African-American children than previously appreciated. Population-based incidence studies will be necessary to determine whether or not our experience has become a more widespread phenomenon.

Adolescent↗
PubMed1997

Vaginal pH as a marker for bacterial pathogens and menopausal status.

OBJECTIVE: Our purpose was to confirm the elevation of vaginal pH expected in patients with bacterial pathogens in premenopausal women and to examine the relationship of serum follicle-stimulating hormone and estradiol levels to vaginal pH in menopausal patients without and with hormone replacement therapy. STUDY DESIGN: Vaginal pH was determined by phenaphthazine (Nitrazine) pH paper in 253 patients seen in a solo private practice for routine speculum examination. None of the patients were pregnant. Measurements were made of serum levels of follicle-stimulating hormone and estradiol for 172 patients and vaginal cultures were taken from 82 patients. Vaginal pH was correlated with vaginal cultures and serum follicle-stimulating hormone and estradiol levels by use of statistical analysis. RESULTS: Vaginal pH was elevated in all premenopausal patients with documented bacterial pathogens. Serum estradiol levels showed an inverse and serum follicle-stimulating hormone levels a direct statistical correlation with vaginal pH in menopausal patients. CONCLUSIONS: Measurement of vaginal pH is useful, effective, and inexpensive for screening purposes. A vaginal pH of 4.5 is consistent with a premenopausal serum estradiol level and the absence of bacterial pathogens. An elevated vaginal pH in the 5.0 to 6.5 range suggests a diagnosis of either bacterial pathogens or decreased serum estradiol. In patients with an elevated pH, vaginal culture should establish the diagnosis. In the absence of bacterial pathogens, a vaginal pH of 6.0 to 7.5 is strongly suggestive of menopause. Titration of estradiol level by vaginal pH during estrogen replacement therapy may help menopausal women avoid side effects or cessation of therapy.

Adult↗
PubMed1997

Iatrogenic renal vascular injuries and their radiological management.

Twenty-nine patients with significant haematuria after a renal invasive procedure (27 of whom had undergone a percutaneous renal procedure and 2 surgical pyelolithotomy) were investigated with angiography. Out of the 21 patients with evidence of arterial injury, 19 were treated by transarterial embolization with gelfoam with or with hydrogel particles; (n = 11), steel coils with gelfoam (n = 4), hydrogel particles (n = 1), surgicel (n = 2), silk with gelfoam (n = 1). The efficacy and technique of the therapeutic embolization procedure is emphasized.

Aneurysm, False↗
PubMed1997

Omega-3 polyunsaturated fatty acids inhibit migration of human vascular smooth muscle cells in vitro.

Arterial smooth muscle cell migration from the media to the intima is a crucial process in the pathogenesis of atherosclerosis. Platelet-derived growth factor (PDGF) has been proposed to play a key role in the development of advanced atherosclerotic lesions by stimulating the migration and proliferation of vascular smooth muscle cells. Polyunsaturated fatty acids (PUFA) of the omega-3 series, extracted from fish oil has been shown to have beneficial effects on atherosclerosis. In this study, we evaluated the effects of omega-3 PUFA on the migration of human aortic smooth muscle cell (hASMC) in vitro. The migration assay was performed according to the Capsoni's method using transwell culture plates. PDGF, fibrinogen or 10% FCS significantly stimulated hASMC migration, however, omega-3 PUFA significantly inhibited PDGF-induced migration of hASMC. These results suggest that the inhibitory effect of omega-3 PUFA on cell migration may be an important aspect by which omega-3 PUFA exerts its antiatherosclerotic influence.

Cell Movement↗
PubMed1997

Nonoperative causes of abdominal pain.

In conclusion, it is good practice to consider operative (life-threatening) entities before nonoperative processes in the differential diagnosis of abdominal pain. However, a prudent and educated surgeon considers, even if only briefly, all possibilities before proceeding to operation.

Abdominal Muscles↗
PubMed1997

Antioxidant responses to simulated acid rain and heavy metal deposition in birch seedlings.

This study measured the responses of different anti-oxidants in 2-year-old birch (Betula pendula Roth) seedlings subjected to simulated acid rain (pH 4.0) and heavy metals (Cu/Ni), applied alone or in combination for 2 months. The applied concentrations of pollutants did not significantly affect seedling biomass or total glutathione levels. Acid rain alone increased superoxide dismutase (SOD) activity both in leaves and roots, while heavy metals alone inhibited SOD activity in roots. Both acid rain and heavy metals applied singly increased ascorbate peroxidase (APX) and guaiacol peroxidase (GPX) activities in leaves but decreased activities in roots. In contrast, acid rain and heavy metal treatments increased glutathione reductase (GR) activity in roots but not in leaves. Spraying birch seedlings with a mixture of acid rain and heavy metals increased SOD, APX and GPX activities in leaves and GR activity in roots. However, the effects of mixed pollutants on enzyme activities usually were less than the summed effects of individual pollutants. Enzyme responses also depended on where pollutants were applied: spraying pollutants onto the shoots initiated higher responses in SOD, APX and GPX than did application to the soil surface, while the opposite was true for GR.

Journal Article↗
PubMed1997

Airborne pollutants along a roadside: assessment using snow analyses and moss bags.

Vertical snow sampling and moss bag transplants were used to estimate the local inorganic and organic pollutant load deposited from traffic along a major highway in Finland. The pH and concentrations of Cl(-), NO(3)(-), SO(4)(2-), Ca(2+), Na(+) and polyaromatic hydrocarbons (PAHs) were determined from snow samples collected in winter at different sites along the highway. In summer, moss bags containing 20 g of fresh red-stemmed feather moss (Pleurozium schreberi) were transplanted at the same sites. The moss bag transplants remained exposed to roadside traffic for a period of one month following which the samples were collected and the PAH profiles and concentrations were analysed. The deposition of inorganic and organic pollutants from road traffic was observed up to 60 m from the road. The prevailing winds had a significant effect on the dispersion of pollutants. Snow appears to be a good collector of inorganic pollutants from the atmosphere and can be used to monitor local airborne pollution from road traffic. Snow packs can also be used as passive collectors of organic pollutant loads from road traffic on a local scale. To monitor organic PAH deposition from the road traffic, moss bags appeared to be better indicators compared to snow sampling. The efficiency of moss bags in accumulating PAH compounds indicate that vegetation may be an important sink for traffic pollution.

Journal Article↗
PubMed1997

Regulation of cellular thiols in human lymphocytes by alpha-lipoic acid: a flow cytometric analysis.

Modulation of cellular thiols is an effective therapeutic strategy, particularly in the treatment of AIDS. Lipoic acid, a metabolic antioxidant, functions as a redox modulator and has proven clinically beneficial effects. It is also used as a dietary supplement. We utilized the specific capabilities of N-ethylmaleimide to block total cellular thiols, phenylarsine oxide to block vicinal dithiols, and buthionine sulfoximine to deplete cellular GSH to flow cytometrically investigate how these thiol pools are influenced by exogenous lipoate treatment. Low concentrations of lipoate and its analogue lipoamide increased Jurkat cell GSH in a dose-dependent manner between 10 (25 microM for lipoamide) to 100 microM. This was also observed in mitogenically stimulated peripheral blood lymphocytes (PBL). Studies with Jurkat cells and its Wurzburg subclone showed that lipoate dependent increase in cellular GSH was similar in CD4+ and - cells. Chronic (16 week) exposure of cells to lipoate resulted in further increase of total cellular thiols, vicinal dithiols, and GSH. High concentration (2 and 5 mM) of lipoate exhibited cell shrinkage, thiol depletion, and DNA fragmentation effects. Based on similar effects of octanoic acid, the cytotoxic effects of lipoate at high concentration could be attributed to its fatty acid structure. In certain diseases such as AIDS and cancer, elevated plasma glutamate lowers cellular GSH by inhibiting cystine uptake. Low concentrations of lipoate and lipoamide were able to bypass the adverse effect of elevated extracellular glutamate. A heterogeneity in the thiol status of PBL was observed. Lipoate, lipoamide, or N-acetylcysteine corrected the deficient thiol status of cell subpopulations. Hence, the favorable effects of low concentrations of lipoate treatment appears clinically relevant.

Acetylcysteine↗
PubMed1997

Adjustable temporary venous spring filter: in vitro assessment.

RATIONALE AND OBJECTIVES: The authors performed an in vitro study to evaluate a temporary venous spring filter that can extend vessels of a wide range of diameters to a slit-shaped canal. MATERIALS AND METHODS: Filters were placed in thin polyethylene tubes or in porcine inferior vena cava specimens (diameter, 10.0-16.0 mm). Physiologic saline was substituted for blood flow, and blood clots of three sizes (6 x 10, 6 x 20, and 9 x 20 mm) were funneled to the filter. Clot-trapping ability was assessed by the degree of luminal extension. RESULTS: When the luminal extension was increased from 2.6r to 2.8r (where r is the original radius of the vein models), clot-trapping ability increased significantly (61.1%-87.5% in polyethylene tubes and 15.8%-77.5% in venous specimens, P < .001). When the luminal extension was increased to 3.0r, more than 90% of the clots were trapped in all tubes. After trapping the small, medium, and large clots, mean intraluminal pressure elevation was 1.0, 1.0, and 17.0 cm of saline, respectively. CONCLUSION: Despite its simple design, the spring filter proved to be an efficient filtering device.

Animals↗
PubMed1997

Detecting native-like properties in combinatorial libraries of de novo proteins.

BACKGROUND: Combinatorial methods based on binary patterning of polar and nonpolar residues have been used to generate large libraries of de novo alpha-helical proteins. Within such libraries, the ability to find structures that resemble natural proteins requires a rapid method to sort through large collections of proteins and detect those possessing 'native-like' features. The current paper presents such a method and applies it to an initial collection of de novo proteins. RESULTS: We present a method to identify proteins with native-like properties from libraries of de novo sequences expressed in vivo. A novel 'rapid prep' freeze/thaw procedure was used to prepare samples; chromatographic purification was not required. The semi-crude samples were analyzed for native-like features by one-dimensional 1H NMR spectroscopy. Using this method, we demonstrate that native-like features can readily be observed for several proteins among a collection of sequences designed by binary patterning of polar and nonpolar amino acids. CONCLUSIONS: Native-like properties can be detected using a method that requires neither isotopic enrichment nor chromatographic purification. The method is inexpensive, rapid, and suitable for parallel processing. It can therefore be employed to screen for native-like properties among large collections of de novo sequences. Using this method, we demonstrate that although the binary code strategy does not explicitly design tertiary packing, it can nonetheless generate proteins that possess native-like properties. The use of combinatorial methods to produce large collections of proteins coupled with the availability of a rapid assay for detecting native-like properties will facilitate the design and isolation of novel proteins with desirable properties.

Chromatography↗
PubMed1997

Impaired nitric oxide-mediated vasodilatation and total body nitric oxide production in healthy old age.

1. Basal release of nitric oxide from the vascular endothelium maintains a constant vasodilating tone. Impaired nitric oxide-mediated vasodilatation has been described in hypertension and atheromatous disease. Circulatory diseases account for considerable morbidity and almost half of all deaths in people over the age of 75 years. 2. We have therefore compared nitric oxide-dependent vasorelaxation in 12 healthy elderly subjects with 12 young volunteers matched for blood pressure, cholesterol and glucose, using forearm occlusion venous plethysmography combined with brachial artery infusions of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA; 1, 2 and 4 mumol/min) with noradrenaline (60, 120 and 240 pmol/min) as a control vasoconstrictor. We also measured urinary nitrate excretion after a controlled 48 h low nitrate diet as an index of total body nitric oxide production and correlated these changes with forearm blood flow responses to L-NMMA and noradrenaline in both groups. 3. The mean age and blood pressure of the elderly subjects was 76 (range 66-82) years and 132/76 (SEM 4/3) mmHg respectively, while in the young these were 27 (20-35) years and 131/72 (4/3) mmHg respectively. L-NMMA and noradrenaline produced dose-dependent reductions in forearm blood flow in both groups. L-NMMA (4 mumol/min) produced less vasoconstriction in the elderly than in the young (-37.7 +/- 2.6 versus -48.3 +/- 4.2%; P = 0.017). The mean slope of the L-NMMA dose-response curves in the elderly was significantly less than the younger group (-35.2 +/- 3.1 versus -63.7 +/- 10.6; P = 0.041). Noradrenaline, 240 pmol/min, also produced less vasoconstriction in the elderly compared with the young (-22.8 +/- 2.9 versus -35.3 +/- 5.0%; P = 0.029) although the slopes of the dose-response curves did not differ significantly. 4. Urinary nitrate adjusted for creatinine clearance was also significantly higher in the younger group (460.6 +/- 97.7 versus 205.9 +/- 64.8 mumol/day; P = 0.042) and showed a significant correlation with the percentage change in forearm blood flow in response to the maximum dose of L-NMMA (r = 0.5, P = 0.046). 5. We conclude that nitric oxide-mediated vasodilatation in the forearm vascular bed is diminished in old age and this reflects a more generalized reduction in nitric oxide production (as measured by urinary nitrate) in the circulation of older people. The blunted response to noradrenaline points to a more generalized reduction in vascular reactivity in the elderly.

Adult↗
PubMed1997

The major elderberry (Sambucus nigra) fruit protein is a lectin derived from a truncated type 2 ribosome-inactivating protein.

The major protein of elderberry (Sambucus nigra L.) fruits is a lectin, called Sambucus nigra agglutinin IVf or SNAIVf. This lectin is composed of subunits that strongly resemble the B chain of the type 2 ribosome-inactivating protein (RIP), called SNAVf, present in the same tissue. To corroborate the possible relationship between both proteins their corresponding cDNAs were cloned and compared. Alignment of the deduced amino acid sequences revealed that the cDNA encoding SNAIVf is almost identical to that of SNAVf except that its A chain is truncated. Northern blot analysis confirmed that the mRNA encoding SNAIVf is about 500 nucleotides shorter than the SNAVf mRNA. In addition, the occurrence of a truncated type 2 RIP gene was unambiguously demonstrated by the analysis of PCR amplified genomic sequences. These results not only demonstrate for the first time that a plant lectin is encoded by a truncated type 2 RIP gene but also address important questions with respect to the molecular evolution of RIP and lectins.

Amino Acid Sequence↗
PubMed1997

Role of zinc in tRNA-acceptor stem binding by glutamyl-tRNA synthetase from E.coli: a molecular modeling study.

A model of the N-terminal half of glutamyl-tRNA synthetase from E. coli was constructed on the basis of similarity in sequence and function of Glutaminyl- and Glutamyl-tRNA synthetases. The glutaminyl-tRNA synthetase does not contain any zinc atom, but glutamyl-tRNA synthetase from E. coli contains one atom of zinc. The specific role of zinc is not yet known. In this article, molecular modeling is employed to show that the zinc atom is well outside the contact region of the acceptor stem of tRNA. The placement of a zinc atom at a significant distance from the tRNA acceptor stem indicates that the role of zinc is likely to be indirect and structural.

Amino Acid Sequence↗
PubMed1997

Renal cystic disease in tuberous sclerosis: role of the polycystic kidney disease 1 gene.

Tuberous sclerosis is an autosomal dominant trait characterized by the development of hamartomatous growths in many organs. Renal cysts are also a frequent manifestation. Major genes for tuberous sclerosis and autosomal dominant polycystic kidney disease, TSC2 and PKD1, respectively, lie adjacent to each other at chromosome 16p13.3, suggesting a role for PKD1 in the etiology of renal cystic disease in tuberous sclerosis. We studied 27 unrelated patients with tuberous sclerosis and renal cystic disease. Clinical histories and radiographic features were reviewed, and renal function was assessed. We sought mutations at the TSC2 and PKD1 loci, using pulsed field- and conventional-gel electrophoresis and FISH. Twenty-two patients had contiguous deletions of TSC2 and PKD1. In 17 patients with constitutional deletions, cystic disease was severe, with early renal insufficiency. One patient with deletion of TSC2 and of only the 3' UTR of PKD1 had few cysts. Four patients were somatic mosaics; the severity of their cystic disease varied considerably. Mosaicism and mild cystic disease also were demonstrated in parents of 3 of the constitutionally deleted patients. Five patients without contiguous deletions had relatively mild cystic disease, 3 of whom had gross rearrangements of TSC2 and 2 in whom no mutation was identified. Significant renal cystic disease in tuberous sclerosis usually reflects mutational involvement of the PKD1 gene, and mosaicism for large deletions of TSC2 and PKD1 is a frequent phenomenon.

Adolescent↗
PubMed1997

Tumor necrosis factor promoter polymorphism and susceptibility to lepromatous leprosy.

Genetically determined differences in immune responses to environmental agents may underlie susceptibility to many autoimmune and infectious diseases. Leprosy provides an example of a polarity in the type of immune response made to an infectious agent, and there is evidence that the major histocompatibility complex is genetically linked to leprosy type. It was found that HLA-DR2 is associated with both tuberculoid and lepromatous types of leprosy; however, a variant at position -308 of the promoter of the neighboring tumor necrosis factor (TNF) gene was increased in frequency in lepromatous (odds ratio = 3.0, P = .02) but not tuberculoid leprosy. Some studies have found higher serum levels of TNF in lepromatous than tuberculoid leprosy, and high TNF levels are found in malaria and leishmaniasis, which are also associated with this TNF allele. It is speculated that this association reflects genetic variability in cytokine production, which influences the immune response to and clinical outcome of leprosy.

Adult↗