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Biomedical subjects

S Ray

Publications and source records attributed to S Ray.

At least 55 records · Page 3Linked to original sources
PubMed2001

Identification of a critical lysine residue at the active site in glyceraldehyde-3-phosphate dehydrogenase of Ehrlich ascites carcinoma cell. Comparison with the rabbit muscle enzyme.

The involvement of the lysine residue present at the active site of Ehrlich ascites carcinoma (EAC) cell glyceraldehyde-3-phosphate dehydrogenase (Gra3PDH) was investigated by using the lysine specific reagents trinitrobenzenesulfonic acid (TNBS) and pyridoxal phosphate (PP). Both TNBS and PP inactivated EAC cell Gra3PDH with pseudo-first-order kinetics with the rate dependent on modifier concentration. Kinetic analysis, including a Tsou plot, indicated that both TNBS and PP apparently react with one lysine residue per enzyme molecule. Two of the substrates, d-glyceraldehyde-3-phosphate and NAD, and also NADH, the product and competitive inhibitor, almost completely protected the enzyme from inactivation by TNBS. A comparative study of Gra3PDH of EAC cell and rabbit muscle indicates that the nature of active site of the enzyme is significantly different in these two cells. A double inhibition study using 5,5'-dithiobis(2-nitrobenzoic acid) and TNBS and subsequent reactivation of only the rabbit muscle enzyme by dithiothreitol suggested that a cysteine residue of this enzyme possibly reacts with TNBS. These studies on the other hand, confirm that an essential lysine residue is involved in the catalytic activity of the EAC cell enzyme. This difference in the nature of the active site of EAC cell Gra3PDH that may be related to the high glycolysis of malignant cells has been discussed.

Amino Acid Sequence↗
PubMed2001

A new strategy for modulating chemotherapy-induced alopecia, using PTH/PTHrP receptor agonist and antagonist.

Parathyroid hormone (PTH) related peptide (PTHrP) and the PTH/PTHrP receptor (PTH/PTHrP-R) show prominent cutaneous expression, where this signaling system may exert important paracrine and/or autocrine functions, such as in hair growth control. Chemotherapy-induced alopecia - one of the fundamental unsolved problems of clinical oncology - is driven in part by defined abnormalities in hair follicle cycling. We have therefore explored the therapeutic potential of a PTH/PTHrP-R agonist and two PTH/PTHrP-R antagonists in a mouse model of cyclophosphamide-induced alopecia. Intraperitoneal administration of the agonist PTH(1-34) or the antagonists PTH(7-34) and PTHrP(7-34) significantly altered the follicular response to cyclophosphamide in vivo. PTH(7-34) and PTHrP(7-34) shifted it towards a mild form of "dystrophic anagen", associated with a significant reduction in apoptotic (TUNEL+) hair bulb cells, thus mitigating the degree of follicle damage and retarding the onset of cyclophosphamide-induced alopecia. PTH(1-34), in contrast, forced hair follicles into "dystrophic catagen", associated with enhanced intrafollicular apoptosis. We had previously shown that an induced shift in the follicular damage-response towards "dystrophic catagen" mitigates cyclophosphamide-induced alopecia, whereas a shift towards "dystrophic catagen" initially enhanced the hair loss, yet subsequently promoted accelerated hair follicle recovery. Therefore, this study in an established animal model of chemotherapy-induced alopecia, which closely mimics human chemotherapy-induced alopecia, strongly encourages the exploration of PTH/PTHrP-R agonists and antagonists as novel therapeutic agents in chemotherapy-induced alopecia.

Alopecia↗
PubMed2001

8-Cl-adenosine induces growth arrest without differentiation of primary mouse epidermal keratinocytes.

In some cell systems, the antiproliferative effects of 8-Cl-cAMP, a site-selective cAMP analog specific for the type I cAMP-dependent protein kinase, are mediated by its metabolite, 8-Cl-adenosine. These effects were once thought to be specific to transformed cells. We investigated the ability of 8-Cl-adenosine to regulate growth and differentiation in primary cultures of mouse epidermal keratinocytes. A 24 h exposure of keratinocytes to 8-Cl-adenosine inhibited [3H]thymidine incorporation in a dose-dependent manner with an apparent IC(50) of 7.5 microM, and these effects were completely reversible. To determine the ability of 8-Cl-adenosine to induce differentiation of primary keratinocytes, we measured keratin-1 expression and transglutaminase activity, markers of early and later stages of keratinocyte differentiation, respectively. Interestingly, exposure of keratinocytes to 25 microM 8-Cl-adenosine for 24 h had no effect on keratin-1 expression or transglutaminase activity. The 8-Cl-adenosine-induced growth arrest of keratinocytes required uptake of the compound and was accompanied by an increase in protein expression of the cyclin-dependent protein kinase inhibitor p21(WAF1/Cip1). These results demonstrate that 8-Cl-adenosine inhibits growth in a non-transformed/non-immortalized cell system, possibly through an elevation in p21(WAF1/Cip1) protein levels, without inducing differentiation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Does extubation result in haemodynamic instability in patients following coronary artery bypass grafts?

Coronary heart disease and its management continue to be at the centre of Government health policy. The present political climate demands clinical effectiveness and best practice should be established, while maintaining the philosophy of cost-effectiveness and resource management. These directives have led practitioners to question the care of patients following coronary artery bypass surgery, in particular the role of mechanical ventilation and the subsequent act of extubation. A retrospective study of 89 patients who had coronary artery bypass grafts (emergency and elective) was undertaken, to establish if extubation had a significant effect on the haemodynamic status of patients with variable degrees of left ventricular function (19% with poor left ventricular function). The study found that extubation was achieved within a mean time of 4.97 hours following return from surgery. Extubation resulted in a significant increase in heart rate (P = 0.001), as well as a respiratory acidosis (pCO2: P = 0.000; pH: P = 0.000). However, the stability of the patient was not compromised, with neither mean arterial blood pressure (P = 0.825) nor oxygenation levels (P = 0.267) being significantly altered by extubation. On multivariate analysis, the act of extubation had no significant effect on any of the dependent variables. These results suggest that it is not extubation alone that has an impact on the haemodynamic stability of patients following coronary artery bypass grafts, but that this is indeed multifactorial. Therefore extubation is 'safe' practice for patients with varying degrees of left ventricular function following coronary artery bypass grafts. Limitations of the study are acknowledged.

Adult↗
PubMed2001

Production of withaferin A in shoot cultures of Withania somnifera.

Multiple shoot cultures of Withania somnifera were established from single shoot tip explants and their potential for the production of two principle withanolides, withaferin A and withanolide D was investigated. Shoot tips grown on MS medium supplemented with BA (1 mg l(-1)) induced 10.0 +/- 1.15 microshoots per explants and shoot cultures accumulated both withanolides (withaferin A = 0.04%, withanolide D = 0.06%). Supplementation of MSSM (solid) agar medium with 4% sucrose enhanced accumulation of both withaferin A (0.16%) and withanolide D (0.08%). Reduction of the agar concentration to 0.16% increased the number of microshoots induced per explant to 25.5. MSSM liquid medium containing 10% coconut milk favoured a maximum increase in biomass (27 fold); number of microshoots induced (37.6 +/- 1.45) as well as accumulation of withaferin A (0.14%).

Adenine↗
PubMed2001

Hepatitis C virus: immunosuppression by complement regulatory pathway.

Hepatitis C virus (HCV) infection in humans is almost invariably associated with viral persistence and chronic hepatitis. HCV-induced chronic hepatitis is a major risk factor for the development of hepatocellular carcinoma. The high incidence of HCV persistence suggests that this virus has evolved one or more mechanisms to evade and possibly suppress host immune responses. To understand the mechanism(s) involved in the establishment of HCV persistence, we have identified an HCV core protein as an immunomodulatory molecule to suppress host immune response. We have further determined a molecular mechanism of HCV core-mediated immune suppression by searching for a potential host protein(s) capable of associating with the HCV core protein. Interestingly, the Clq complement receptor, gC1qR, can bind to the HCV core. Clq is a ligand of gClqR and is involved in the early defense against viral infection as well as regulation of adaptive immune response. Similar to Clq, the HCV core can inhibit human T-lymphocyte proliferative response through its interaction with the gC1qR. It implicates that HCV core/gClqR-induced immune suppression may play a critical role in the establishment of persistent infection.

Animals↗
PubMed2001

Topical triiodothyronine stimulates epidermal proliferation, dermal thickening, and hair growth in mice and rats.

The skin is a classic target tissue for thyroid hormone action. Although the histology of skin in hypothyroid states is well documented, the literature contains little assessment of skin in thyrotoxic states. In light of the paucity of information on skin under the influence of excess thyroid hormone, we investigated the direct effect of thyroid hormone on skin. Triiodothyronine (T3) was applied topically daily in liposomes to SKH-1 hairless mice for 7 days and to CD rats for 2 weeks. There was a dose-dependent increase in epidermal proliferation, dermal thickening, and hair growth in T3-treated animals. Mice that received 3.8 microg of T3 had 42% more hairs per millimeter than controls (p < 0.01), hair length that was 1,180% longer (p < 0.001), 49% greater epidermal 3H-thymidine incorporation (p < 0.01), and 80% more 5-bromo-2'-deoxyuridine (BrdU) stained cells (p < 0.05). Rats receiving 12.8 microg T3 had 48% greater dermal thickness than controls (p < 0.001), 26% greater epidermal thickness (p < 0.001), 85% more hairs per millimeter (p < 0.005), and 130% greater 3H-thymidine incorporation into the epidermis (p < 0.01). Thus, topically applied thyroid hormone has dramatic effects on both skin and hair growth. These observations offer a new strategy for developing thyroid hormone and its analogues for treating disorders of skin and hair growth.

Administration, Topical↗
PubMed2001

Requirement of the Lec35 gene for all known classes of monosaccharide-P-dolichol-dependent glycosyltransferase reactions in mammals.

The Lec35 gene product (Lec35p) is required for utilization of the mannose donor mannose-P-dolichol (MPD) in synthesis of both lipid-linked oligosaccharides (LLOs) and glycosylphosphatidylinositols, which are important for functions such as protein folding and membrane anchoring, respectively. The hamster Lec35 gene is shown to encode the previously identified cDNA SL15, which corrects the Lec35 mutant phenotype and predicts a novel endoplasmic reticulum membrane protein. The mutant hamster alleles Lec35.1 and Lec35.2 are characterized, and the human Lec35 gene (mannose-P-dolichol utilization defect 1) was mapped to 17p12-13. To determine whether Lec35p was required only for MPD-dependent mannosylation of LLO and glycosylphosphatidylinositol intermediates, two additional lipid-mediated reactions were investigated: MPD-dependent C-mannosylation of tryptophanyl residues, and glucose-P-dolichol (GPD)-dependent glucosylation of LLO. Both were found to require Lec35p. In addition, the SL15-encoded protein was selective for MPD compared with GPD, suggesting that an additional GPD-selective Lec35 gene product remains to be identified. The predicted amino acid sequence of Lec35p does not suggest an obvious function or mechanism. By testing the water-soluble MPD analog mannose-beta-1-P-citronellol in an in vitro system in which the MPD utilization defect was preserved by permeabilization with streptolysin-O, it was determined that Lec35p is not directly required for the enzymatic transfer of mannose from the donor to the acceptor substrate. These results show that Lec35p has an essential role for all known classes of monosaccharide-P-dolichol-dependent reactions in mammals. The in vitro data suggest that Lec35p controls an aspect of MPD orientation in the endoplasmic reticulum membrane that is crucial for its activity as a donor substrate.

Acyclic Monoterpenes↗
PubMed2001

Constraints faced by sex workers in use of female and male condoms for safer sex in urban zimbabwe.

We investigated whether female condoms are acceptable to sex workers in Harare and whether improved access to male and female condoms increases the proportion of protected sex episodes with clients and boyfriends. Sex workers were randomly placed in groups to receive either male and female condoms (group A, n = 99) or male condoms only (group B, n = 50) and were followed prospectively for about 3 months each. We found a considerable burden of human immunodeficiency virus (HIV) and sexually transmitted infections (STIs) in our cohort at enrollment (86% tested HIV positive and 34% had at least one STI). Consistent male condom use with clients increased from 0% to 52% in group A and from 0% to 82% in group B between enrollment and first follow-up 2 weeks later and remained high throughout the study. Few women in group A reported using female condoms with clients consistently (3%-9%), and use of either condom was less common with boyfriends than with clients throughout the study (8%-39% for different study groups, visits, and types of condom). Unprotected sex still took place, as evidenced by an STI incidence of 16 episodes per 100 woman-months of follow-up. Our questionnaire data indicated high self-reported acceptability of female condoms, but focus group discussions revealed that a main obstacle to female condom use was client distrust of unfamiliar methods. This study shows that a simple intervention of improving access to condoms can lead to more protected sex episodes between sex workers and clients. However, more work is needed to help sex workers achieve safer sex in noncommercial relationships.

Adult↗
PubMed2001

Neuroretinitis.

Despite the growing list of agents that can present as neuroretinitis, nearly one-half remain idiopathic. However, many of the candidate etiologies are treatable conditions, and accurate diagnosis can result in visual rehabilitation. A complete workup in patients presenting with acute neuroretinitis should include a thorough history and general medical evaluation. Exposure history should be thoroughly explored, including recent travel, unpasteurized and uncooked foods, sexual experience, and animal contacts. A detailed physical examination should be performed to note hidden rashes and inoculation sites and should include routine measurements of blood pressure and heart rate. Laboratory tests should be tailored to the history and may include complete blood count; erythrocyte sedimentation rate; bacterial, fungal, and viral blood cultures; antinuclear antibody test; angiotensin-converting enzyme; anti-double-stranded DNA; and C3. Serological evaluation should look for syphilis, Lyme disease, histoplasmosis, brucellosis, chlamydia, HIV, toxoplasmosis, Epstein-Barr virus, viral hepatitis B and C, and tuberculin skin test. Neuroretinitis is a clinical entity in which there is inflammation of the retinal architecture and optic nerve. There are numerous entities that can cause a picture of neuroretinitis ranging from vascular to infectious to autoimmune. With regards to the infectious etiologies, it is interesting to note that many of these organisms are obligate intracellular pathogens. The microorganisms B. henselae, T. gondii, R. typhi, T. pallidum, Mycobacterium tuberculosis, Histoplasma capsulatum, and various viruses, such as HIV, mumps, and HSV, are known intracellular agents. Other major infectious agents, such as B. burgdorferi and Leptospirosis spp. are known to remain sequestered within the circulatory system. It is possible that in this way these agents are able to breach the delicate blood-brain barrier. The implication of such findings on the treatment and management of neuroretinitis remains to be explored. Interestingly, the vast majority of infected patients do not develop neuroretinitis or demonstrate CNS involvement. Detailed examination of this variability may provide further insight into the pathogenic properties of these infectious agents, host tissue susceptibility, and mechanisms of blood-retina barrier integrity. A detailed retinal examination can provide an unobstructed view of the CNS. Careful inspection of this delicate interface may reveal subtle findings critical for accurate and rapid diagnosis of underlying systemic pathology. The varied visual and neurological symptoms of neuroretinitis attest to the fact that this is a disease of both the retina and contiguous neuronal elements. Such involvement significantly elevates the risk to the patient and emphasizes the need for early detection and prompt treatment.

Humans↗
PubMed2001

The Florida "truth" anti-tobacco media evaluation: design, first year results, and implications for planning future state media evaluations.

OBJECTIVES: To outline the design and present selected findings from the evaluation of a state counter-advertising, anti-tobacco media campaign. The appropriateness of the design for states developing media evaluations is discussed. DESIGN: Four cross sectional, telephone surveys of the 12--17 year old population were used to track and monitor advertising and campaign awareness, confirmed awareness, and receptivity. The Florida baseline and one year surveys were used with two parallel national surveys in a quasi-experimental design to assess attitude and smoking related behaviour change attributable to the campaign. MEASURES: Awareness was measured by self report, confirmed awareness by unaided description, and receptivity by self reports of how well advertisements were liked, talked to friends about, and made one think about whether or not to smoke. Eleven attitude and three smoking behaviour items for Florida (treatment) and a national (control) population were compared at baseline and after 12 months. RESULTS: Significant increases in ad specific awareness, confirmed, receptivity, and campaign awareness, and confirmed awareness were reached by the sixth week. They continued to rise through the first year. No attitude and only minor behaviour differences were noted between the treatment and comparison populations at baseline. By the end of the first year, Florida youth had stronger anti-tobacco attitudes and better behaviour patterns than the comparison population. CONCLUSIONS: The industry manipulation strategy used in the Florida campaign resulted in high rates of recall, significant changes in attitudes/beliefs, and reduced rates of smoking behaviour among youth.

Adolescent↗
PubMed2001

A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If).

We describe a new congenital disorder of glycosylation, CDG-If. The patient has severe psychomotor retardation, seizures, failure to thrive, dry skin and scaling with erythroderma, and impaired vision. CDG-If is caused by a defect in the gene MPDU1, the human homologue of hamster Lec35, and is the first disorder to affect the use, rather than the biosynthesis, of donor substrates for lipid-linked oligosaccharides. This leads to the synthesis of incomplete and poorly transferred precursor oligosaccharides lacking both mannose and glucose residues. The patient has a homozygous point mutation (221T-->C, L74S) in a semiconserved amino acid of MPDU1. Chinese hamster ovary Lec35 cells lack a functional Lec35 gene and synthesize truncated lipid-linked oligosaccharides similar to the patient's. They lack glucose and mannose residues donated by Glc-P-Dol and Man-P-Dol. Transfection with the normal human MPDU1 allele nearly completely restores normal glycosylation, whereas transfection with the patient's MPDU1 allele only weakly restores normal glycosylation. This work provides a new clinical picture for another CDG that may involve synthesis of multiple types of glycoconjugates.

Adolescent↗
PubMed2001

Influence of a counteradvertising media campaign on initiation of smoking: the Florida "truth" campaign.

OBJECTIVES: The purpose of this study was to assess the short-term effects of television advertisements from the Florida "truth" campaign on rates of smoking initiation. METHODS: A follow-up survey of young people aged 12 to 17 years (n = 1820) interviewed during the first 6 months of the advertising campaign was conducted. Logistic regression analyses were used to estimate the independent effects of the campaign on smoking initiation while other factors were controlled for. RESULTS: Youths scoring at intermediate and high levels on a media effect index were less likely to initiate smoking than youths who could not confirm awareness of television advertisements. Adjusted odds ratios between the media index and measures of initiation were similar within categories of age, sex, susceptibility, and whether a parent smoked. CONCLUSIONS: Exposure to the "truth" media campaign lowered the risk of youth smoking initiation. However, the analysis did not demonstrate that all such media programs will be effective.

Adolescent↗
PubMed2001

Anticlastogenic effects of d- and l-centchroman in Swiss albino mice. 2. Subacute study in vivo and comparison with tamoxifen.

The antimutagenic effects of the two enantiomers of centchroman, a nonsteroidal oral contraceptive, were evaluated and compared with tamoxifen, a known breast cancer drug. Anticlastogenic assays in subacute in vivo studies in Swiss albino mice were used. They revealed that both d-centchroman and I-centchroman reduced the chromosome aberrations produced by dimethylbenz(a)anthracene and cyclophosphamide, when compared with the group treated only with the former mutagen. Tamoxifen also reduced the chromosome aberrations produced by the two mutagens. Overall the results showed that l-centchroman alone was more effective in reducing cyclophosphamide-induced aberrations than d-centchroman, and for toxicity reasons may be an alternative to tamoxifen in breast cancer therapy.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Integrin modulating factor: a 30-kD protein that modulates the expression and function of alpha5beta1 integrin receptor.

The integrin family of cell surface receptors consists of transmembrane glycoproteins involved in cellular morphology, cytoarchitecture, cell-cell, and cell-extracellular matrix interaction. Changes in integrin receptor expression are associated with malignant transformation. The adhesion promoting activity of several members of the integrin receptors may be modulated. Integrin Associated Proteins and integrin modulating factor that may modulate integrin receptors expression and function have been reported. In this article, we report the identification of a 30-kD protein produced in SiHa cell culture medium that can modulate the expression and function of alpha5beta1 integrin receptor in HeLaS3 cells. The cell adhesion assay clearly demonstrated that HeLaS3 cells grown in a serum-free culture medium of SiHa cells (fresh medium: culture medium = 3:1) stimulated the ligand binding activity of alpha5beta1 receptor to fibronectin in a time-dependent manner, having a peak activity at 72 hours of culture. Immunocytochemical localization showed a very high expression of alpha5beta1 receptor in HeLaS3 cells grown in a SiHa culture medium for 72 hours. The (NH4)2SO4 fractionation demonstrated that proteins present in 80-100% (NH4)2SO4 saturated fraction of serum-free SiHa culture medium have a significant stimulatory effect on the binding of HeLaS3 cells to fibronectin ligand via the alpha5beta1 integrin receptor. High pressure liquid chromatography (HPLC) separation of 80-100% (NH4)2SO4 saturated fraction showed a 30- kD protein in polyacrylamide gel electrophoresis (PAGE) analysis that has a maximum stimulatory effect on the binding of HeLaS3 cells to fibronectin ligand via the alpha5beta1 integrin receptor. In conclusion, our observations indicated that human cervical tumor cells SiHa produce a 30-kD protein that can modulate the expression and function of alpha5beta1 fibronectin integrin receptor of HeLaS3 cells. These findings strengthen the concept that some cellular proteins, also called Integrin Associated Protein, may regulate the integrin receptor expression and function. Studies are in progress to characterize this 30-kD integrin modulating factor and its role in the regulation of integrin receptor function.

Binding Sites↗
PubMed2001

Role of alphavbeta3 integrin receptors in breast tumor.

The intriguing problem of tumor metastasis involves adhesion of the metastatic cells via the integrin group of cell surface receptors to the ECM proteins of the basement membrane. Modulation of integrin family of cell surface receptors is believed to be associated with stages of tumor metastasis. In this present study, results obtained indicate that alphavbeta3 vitronectin receptors may play an important role in the malignant behaviour of human breast tumor. Alphavbeta3 integrin receptors can modulate the activity of collagenase enzyme and thereby the invasive property of breast tumor cells.

Breast Neoplasms↗
PubMed2001

Action of an algicide from a cyanobacterium, Oscillatoria laetevirens, on photosystem II.

Oscillatoria laetevirens produces an algicide, named oscillatorin (OS), which inhibits growth of higher plants. Effect of purified oscillatorin and some 'urea-triazine type' herbicides was studied on photosystem II activity and composition of pigment protein complex in spinach thylakoid membrane. For oscillatorin the I50 at 10 microg chlorophyll concentration, inhibitor constant (Ki), specific binding sites and Hill coefficient were calculated to be 1.45, 0.15, 2.3 and 0.2 microM respectively. Metribuzin and oscillatorin affected towards the donor side and brought about identical changes in polypeptide composition of PSII complex. Further, metribuzin and atrazine exerted antagonistic and synergistic responses on oscillatorin action. Some of these parameters were also studied on weed plants to assess upon the weedicidal potential of oscillatorin.

Cyanobacteria↗