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Biomedical subjects

S Ray

Publications and source records attributed to S Ray.

At least 181 records · Page 10Linked to original sources
PubMed1995

Saracin: a lectin from Saraca indica seed integument recognizes complex carbohydrates.

A lectin isolated from Saraca indica seed integument was purified by affinity chromatography on porcine thyroglobulin Sepharose followed by Sephadex G-50 and shown to be homogeneous by PAGE. It showed a single band on SDS-PAGE in the absence and presence of 2-mercaptoethanol corresponding to a M(r) of congruent to 12,000, thus indicating it to be a monomer. The lectin agglutinated erythrocytes of human A, B, O and AB blood group, animal erythrocytes as well as Ehrlich ascites cells. It is a thermostable glycoprotein containing 11.6% carbohydrates and large proportions of acidic amino acids. In haemagglutination-inhibition assays, among the tested glycoproteins, porcine thyroglobulin having the NeuAc alpha (2-6)/(2-3)D-Gal beta (1-4)D-GlcNAc sequence was found to be the most potent; however, its asialo counterpart was non-inhibitory. The lectin is present solely in the seed integument even in the immature stage. During maturation of the seed the lectin activity declined and was completely absent when totally matured and dried. Studies in vitro showed that on incubation at 37 degrees the seed gradually lost its lectin activity which was completely absent after 62 days with 88.5% loss of water. Similar studies on scraped seed integument revealed that the lectin activity was lost in 22 days with 87.5% dehydration.

ABO Blood-Group System↗
PubMed1995

An approach towards the development of progesterone antagonists: synthesis of 7 alpha/7 beta-aryl androstene derivatives.

Synthesis of 3 beta,17 beta-dihydroxy-7 alpha/7 beta-(4-hydroxyphenyl)-androst-5-ene 3,17-diacetate (4 and 5, R = H) and 3 beta,17 beta-dihydroxy-7 alpha/7 beta-(4-methoxyphenyl)-androst-5-ene 3,17-diacetate (4 and 5, R = Me) have been carried out by Friedel-Crafts reaction on 3 beta,7,17 beta-trihydroxy-androst-5-ene 3,17-diacetate (3, R = H) with phenol and anisole, respectively. Compounds 4 (R = H) and 5 (R = H) have been separated and their stereochemistry assigned on the basis of COSY and NOE experiments.

Androstenols↗
PubMed1995

32P-postlabeling analysis of aromatic DNA-adducts in liver and brain of wild brook trout (Salvelinus fontinalis).

Several studies have reported the absence of DNA-adducts in fish collected from unpolluted areas. We determined DNA-adduct levels in liver and brain tissue of wild brook trout (Salvelinus fontinalis) from remote areas of Newfoundland and sub-arctic Labrador, that have no known input of anthropogenic contamination. Varying levels of adducts were detected in both liver and brain, at all locations. Hepatic adduct levels were generally higher than those in brain tissue. Tissue-specific differences in adduct levels and the possible effects of long range transport of air pollutants (LRTAP) are discussed.

Animals↗
PubMed1995

The Subcutaneous Heparin and Angioplasty Restenosis Prevention (SHARP) trial. Results of a multicenter randomized trial investigating the effects of high dose unfractionated heparin on angiographic restenosis and clinical outcome.

OBJECTIVES: We sought to determine whether 12,500 IU of unfractionated heparin given subcutaneously twice daily for 4 months after percutaneous transluminal coronary angioplasty beneficially influences the subsequent rate of angiographic restenosis and the incidence of clinical events. BACKGROUND: Heparin has been shown to exhibit powerful antiproliferative effects against smooth muscle cells in several animal models. METHODS: A randomized trial with blinded data analysis was undertaken to assess the effect of unfractionated subcutaneous heparin on angiographic restenosis after coronary angioplasty. After successful angioplasty, patients were randomized to receive no heparin or 12,500 IU of heparin given subcutaneously twice daily for 4 months. Quantitative coronary angiography was performed before angioplasty, immediately after angioplasty and at follow-up ("early" [before 4 months] or electively [at 4 months]). RESULTS: The study group comprised 339 patients, 167 randomly assigned to receive heparin, 172 to receive no heparin. Repeat cardiac catheterization was performed in 90% of randomized patients. At early and elective restudy (mean 4.2 months), the mean +/- SD difference in minimal lumen diameter between the postangioplasty and follow-up measurement was -0.55 +/- 0.58 mm for the no heparin group and -0.43 +/- 0.59 mm for the heparin group (p = NS). Clinical events during the follow-up period did not differ significantly between groups: fatal myocardial infarction (1 patient in each group), coronary bypass grafting (5 patients in each group), repeat angioplasty (12 in the no heparin, 6 in the heparin group), angina at 4-month assessment (33% in the no heparin, 32% in the heparin group). CONCLUSIONS: Long-term treatment with high dose subcutaneous heparin (12,500 IU twice daily) for 4 months did not favorably influence angiographic or clinical outcome after coronary angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1995

Differential kinetics of parotid and submandibular gland function as demonstrated by scintigraphic means and its possible implications.

Is the differential kinetics of secretion of saliva between the parotid and submandibular glands responsible for the relative difference in radiosensitivity? Radiation-induced dysfunction is more often noted in the parotid glands than the submandibular glands. This difference in susceptibility is often attributed to the difference in the cellular composition of these glands. During our studies using 99Tcm-pertechnetate to quantitate salivary gland function in patients treated with radioiodine, we noted frequent unstimulated discharge of saliva from the submandibular glands compared with parotid secretion. We hypothesize that the relative resistance of the submandibular glands could be due to the differential kinetics of the parotid and submandibular glands, as evidenced by using 99Tcm-pertechnetate to study their function.

Humans↗
PubMed1995

Needle-using practices within the sex industry. National AIDS Research Consortium.

The addicted prostitute faces a risk of AIDS from both her sexual practices and intravenous drug use. While the sexual practices of these women have been studied, much less is known about their needle-using practices. We suggest women in the sex industry are more enmeshed in the drug-using scene and occupy a more constricted set of social roles than other women. They will therefore lack the resources and have fewer opportunities to engage in safer behaviors compared to women who support themselves by other means. The analysis is based on 9,055 addicted women not in treatment. Women who trade sex for money and/or drugs are less likely to use new needles on any consistent basis or to clean old needles. They are more likely to share needles with others compared to women who support themselves by other means. Three identifiable patterns of needle-using practices emerge: indiscriminate sharing, monogamous sharing with a sexual partner, and exclusive use of new needles. To reach those engaged in promiscuous sharing, needle-swapping programs must be particularly "user friendly." Where needle-using behaviors reflect an intimate relationship, the spouse/sex partner must be engaged if change is to take place. Finally, policymakers and practitioners should capitalize on the strengths and strategies of those who report they consistently use sterile needles.

Acquired Immunodeficiency Syndrome↗
PubMed1995

pIXY321 protects against Ara-C or taxol-induced apoptosis and loss of clonogenic survival of normal human bone marrow progenitor cells.

By suppressing apoptosis, hemopoietic growth factors (HGFs) promote the survival of CD34+, HLA-DR+ marrow cells that are enriched for hemopoietic progenitor cells (HPC). In the present studies, we have examined the effects of pIXY321, a genetically engineered fusion protein of GM-CSF and IL-3 (GM-CSF/IL-3), on high-dose Ara-C (HIDAC) and taxol-induced apoptosis and survival of a multilineage HPC, the CFU-GEMM. Exposure to 1.0 mumol/l taxol for 24 h or HIDAC > or = 10 mumol/l for 4 h induced internucleosomal DNA fragmentation and the morphologic features of apoptosis in CD34+, HLA-DR+ cells. These treatments were associated with > or = 50% inhibition of the assayable CFU-GEMM colony numbers. Incubation in serum-free medium (SFM) alone for 24 h also induced apoptosis of CD34+, HLA-DR+ cells, which was associated with reduced intracellular levels of the bcl-2 gene product p26BCL-2. Co-treatment with pIXY321 (10 ng/ml) inhibited apoptosis of CD34+, HLA-DR+ cells incubated in SFM, without significantly increasing the intracellular p26BCL-2 levels. Furthermore, co-treatment with pIXY321 significantly reduced taxol- and Ara-C-induced apoptosis and promoted the survival of CFU-GEMM (P < 0.05). Taxol and Ara-C mediated apoptosis of CD34+, HLA-DR+ cells, and its inhibition by pIXY321, was not accompanied by any significant alteration in the intracellular p26BCL-2 levels. By demonstrating that co-treatment with pIXY321 confers significant protection against apoptosis of CD34+, HLA-DR+ cells as well as promotes survival of normal HPC exposed to clinically relevant schedules and concentrations of taxol of Ara-C, these results support the design of chemotherapy regimens incorporating pIXY321 plus taxol and/or high-dose Ara-C for solid tumors and/or acute leukemias. It is hoped that the use of such a cytokine might maintain normal HPC numbers following chemotherapy, therefore avoiding prolonged suppression.

Antigens, CD34↗
PubMed1995

Clinical audit of malaria diagnosis in urban primary curative care clinics, Zimbabwe.

Clinical audit was performed on the accuracy of malaria diagnosis by nursing staff within Harare City Health Department using diagnosis by doctors as the reference standard. This was found to be about 10 pc based on symptoms. The criteria for diagnosis of malaria as in ZEDAP manuals and in-house training were not being utilised. Pyrexia was not present in 40 pc of the patients. Serious illnesses were occasionally dismissed as malaria and not treated appropriately or reviewed. The most common misdiagnosis was of acute respiratory tract infections which also have clear guidelines for diagnosis. More appropriate training methods need to be developed to improve the diagnostic capacity of nursing staff who are frontline providers of primary health care. This study shows the importance of performing an audit for process evaluation, compared to set standards and to be used for improving the quality of services.

Adolescent↗
PubMed1995

Effects of modulators of protein kinases on taxol-induced apoptosis of human leukemic cells possessing disparate levels of p26BCL-2 protein.

Taxol-induced polymerization of tubulin into stable microtubules and cell cycle metaphase arrest have been demonstrated to result in internucleosomal DNA fragmentation and morphological features of apoptosis in human leukemia cells. Recent studies have also shown that Taxol-induced apoptosis, but not Taxol-induced microtubular bundling or mitotic arrest, is significantly inhibited in cells that overexpress the bcl-2 gene product p26BCL-2. In the present studies we examined the effects of several modulators of activities of protein kinases on Taxol-induced DNA fragmentation and apoptosis in human pre-B leukemia 697 cells transfected with the cDNA of the bcl-2 gene and expressing high intracellular levels of p26BCL-2 (697/BCL-2 cells). Treatment with 0.1-1.0 microM MTaxol for 24 h produced prolonged mitotic arrest of control 697/neo cells, which had been transfected with the neomycin resistance gene. This resulted in apoptosis-associated large DNA fragments ranging between 5 and 200 kb and internucleosomal DNA fragmentation. Cotreatment with the phorbol ester phorbol dibutyrate (PdBU) significantly reduced Taxol-induced internucleosomal and large DNA fragmentation and inhibited apoptosis of 697/neo cells. In contrast, a combined exposure to Taxol and staurosporine (ST; 5 or 50 ng/ml), a potent inhibitor of protein kinase C and other kinases, significantly increased DNA fragmentation and apoptosis of 697/neo cells. Additionally, in 697/BCL-2 cells, ST partially overcame the suppressive effects of high p26BCL-2 levels on Taxol-induced apoptosis. Cotreatment with the tyrosine kinase inhibitor Genistein (30 microM) markedly inhibited Taxol-induced DNA fragmentation and apoptosis of 697/neo cells. However, it is noteworthy that the modulations of Taxol-induced DNA fragmentation and apoptosis by PdBU, ST, and Genistein occurred without significant effects on Taxol-mediated mitotic arrest of 697/neo cells. These agents also did not affect intracellular p26BCL-2 levels in 697/neo or 697/BCL-2 cells. These findings indicate that Taxol-induced apoptosis can be modulated by agents that affect the activities of protein kinases, and these effects are not mediated by modulations of Taxol-induced mitotic arrest or by alterations of intracellular p26BCL-2 levels.

Antineoplastic Agents, Phytogenic↗
PubMed1995

Evidence against a direct role for the induction of c-jun expression in the mediation of drug-induced apoptosis in human acute leukemia cells.

Previous reports have demonstrated that a variety of anticancer drugs, e.g., 1-beta-D-arabinofuranosylcytosine (ara-C), mitoxantrone, etoposide, camptothecin, and cisplatin, induce the expression of c-jun oncogene in leukemic cells prior to producing internucleosomal DNA fragmentation and the morphological features of apoptosis. This has led to the impression that the induction of c-jun expression may be directly involved in the molecular signaling of the final common pathway of programmed cell death or apoptosis. In the present study, we examined the role of c-jun expression in three different settings of anticancer drug-induced apoptosis in human leukemic cells. First, exposure of human myeloid leukemia HL-60 cells to high-dose ara-C for 4 h produced internucleosomal DNA fragmentation preceded by c-jun induction. However, pretreatment of HL-60 cells with staurosporine, a protein kinase C inhibitor, repressed c-jun yet enhanced DNA fragmentation and apoptosis due to ara-C. Second, in human pre-B leukemia 697/BCL-2 cells which are transfected with the cDNA of the bcl-2 oncogene and overexpress p26BCL-2, although ara-C or mitoxantrone treatment caused greater c-jun induction than in the 697/neo cells, significantly reduced endonucleolytic DNA fragmentation and apoptosis was observed in 697/BCL-2 cells. Finally, taxol-induced internucleosomal DNA fragmentation and morphological features of apoptosis in HL-60 cells were not associated with the induction of c-jun expression. These lines of evidence indicate that the induction of c-jun expression may not have a direct role in the molecular signaling of anticancer drug-induced apoptosis, and that the anticancer drug-induced apoptosis can occur by a mechanism that does not involve the induction of c-jun expression.

Antineoplastic Agents↗
PubMed1994

Lack of allelic exclusion permits autoreactive B cells to escape deletion.

The R4A-gamma 2b transgenic mouse harbors the gene for the gamma 2b heavy chain of an anti-dsDNA Ab. Approximately 80% of B cells expressing the transgene display allelic exclusion. Although the transgenic mice have little to no detectable serum anti-DNA activity, splenic B cells can be stimulated in vitro with LPS to secrete anti-DNA Ab. Hybridomas derived from LPS-stimulated splenic B cells were analyzed for expression of the transgene and for DNA binding. All nine transgene-encoded anti-DNA-producing lines were found to express an endogenous IgM heavy chain. Of 19 randomly selected lines producing a transgene-encoded non-DNA binding Ab, none expressed a second heavy chain. The tight correlation between lack of allelic exclusion and anti-dsDNA specificity provides strong support for the hypothesis that a major function of allelic exclusion is to prevent the maintenance of a pool of potentially activatable autoreactive cells.

Alleles↗
PubMed1994

Inhibition of electron flow through complex I of the mitochondrial respiratory chain of Ehrlich ascites carcinoma cells by methylglyoxal.

The effect of methylglyoxal on the oxygen consumption of Ehrlich-ascites-carcinoma (EAC)-cell mitochondria was tested by using different respiratory substrates, electron donors at different segments of the mitochondrial respiratory chain and site-specific inhibitors to identify the specific respiratory complex which might be involved in the inhibitory effect of methylglyoxal on the oxygen consumption by these cells. The results indicate that methylglyoxal strongly inhibits ADP-stimulated alpha-oxo-glutarate and malate plus pyruvate-dependent respiration, whereas, at a much higher concentration, methylglyoxal fails to inhibit succinate-dependent respiration. Methylglyoxal also fails to inhibit respiration which is initiated by duroquinol, an artificial electron donor. Moreover, methylglyoxal cannot inhibit oxygen consumption when the NNN'N'-tetramethyl-p-phenylenediamine by-pass is used. The inhibitory effect of methylglyoxal is identical on both ADP-stimulated and uncoupler-stimulated respiration. Lactaldehyde, a catabolite of methylglyoxal, can exert a protective effect on the inhibition of EAC-cell mitochondrial respiration by methylglyoxal. We suggest that methylglyoxal possibly inhibits the electron flow through complex I of the EAC-cell mitochondrial respiratory chain.

Aldehydes↗
PubMed1994

A parathyroid hormone antagonist stimulates epidermal proliferation and hair growth in mice.

The biologic action of parathyroid hormone (PTH)-related peptide (PTHrP) in normal skin was investigated in cultured human keratinocytes and in SKH-1 hairless mice. The results indicate that the PTHrP agonists human PTHrP-(1-34) and PTH(1-34) are potent inhibitors of epidermal cell proliferation. [Nle8,18,Tyr34]bovine PTH-(7-34)-amide, an antagonist of the PTH/PTHrP receptor, blocked the inhibitory effect of PTH-(1-34) in cultured keratinocytes. In the SKH-1 mice, PTH-(7-34) caused a 244% increase of [3H]thymidine incorporation into isolated epidermal DNA and 246% and 180% increases in the number and length of hair shafts, respectively. Thus, PTH and PTHrP may play an important role in the normal physiology of skin, and their agonists and antagonists have potentially wide therapeutic applications in the treatment of hyperproliferative skin disorders and aging skin and could also be effective in stimulating and maintaining hair growth.

Animals↗
PubMed1994

Arabidopsis floral homeotic gene BELL (BEL1) controls ovule development through negative regulation of AGAMOUS gene (AG).

Ovules are the developmental precursors of seeds. In angiosperms the ovules are enclosed within the central floral organs, the carpels. We have identified a homeotic mutation in Arabidopsis, "bell" (bel1), which causes transformation of ovule integuments into carpels. In situ hybridization analysis shows that this mutation leads to increased expression of the carpel-determining homeotic gene AGAMOUS (AG) in the mutant ovules. Introduction of a constitutively expressed AG transgene into wild-type plants causes the ovules to resemble those of bel1 mutants. We propose that the BEL1 gene product directs normal integument development, in part by suppressing AG expression in this structure. Our results allow expansion of the current model of floral organ identity to include regulation of ovule integument identity.

Arabidopsis↗
PubMed1994

Generation of a fusion partner to sample the repertoire of splenic B cells destined for apoptosis.

B cells proliferate and diversify in germinal centers in response to antigen. Only a small percentage of these B cells will emerge to form the serum antibody response. Other B cells making lower affinity antibodies, acquiring nonsense mutations, or expressing autoreactivity as a result of somatic mutation undergo an apoptotic cell death and are not efficiently sampled in current analyses of B-cell hybridomas. We have demonstrated that expression of bcl-2 in the NSO myeloma fusion partner leads to a higher yield of viable hybridomas, with a selective increase in hybridomas from B cells that produce autoantibodies and are seldom recovered when spleen cells from non-autoimmune mice are fused to the conventional NSO cell line. Using this fusion partner, we have generated hybridomas from anti-DNA antibody-producing transgenic B cells that are anergic in vivo and destined for apoptosis. These studies provide a strategy to sample the repertoire of B cells that arise in vivo but are not selected to contribute to the expressed antibody response. Furthermore, they demonstrate that restricted expression of bcl-2 in B cells contributes to the maintenance of self-tolerance in secondary lymphoid organs.

Animals↗
PubMed1994

An X-ray crystallographic study of the nonsteroidal contraceptive agent centchroman.

We have determined an X-ray crystal structure for the N-methyl iodide derivative of the nonsteroidal contraceptive centchroman. The pendant aromatic substituents on C-3 and C-4 of the chroman system are nearly perpendicular to the plane of the chroman system, an orientation expected in such a chroman, but perturbed to some degree by the gem dimethyl substituents at C-2. Structural superposition with other nonsteroidal antiestrogens, tamoxifen and nafoxidine, shows a similar disposition of the tertiary amine side chains responsible for antagonist activity. The aryl rings also show good superposition, but in contrast to tamoxifen and nafoxidine, which have the potential for ring double bond conjugation, the centchroman aryl rings show a larger dihedral twist. While different superpositions between the enantiomers of centchroman and the bioactive enantiomer of estradiol (d-estradiol, 8 beta,9 alpha,13 beta,14 alpha,17 beta) are possible, when the chroman ring system is positioned over the AB rings of estradiol, then (3R,4R)-centchroman makes the best fit. The aryl substituents in both enantiomers make comparable overlays with the steroidal skeleton, but the axial methyl group at C-2 in (3R,4R)-centchroman is directed downward along the C-7 alpha axis of estradiol, a site where many substituents are known to be well tolerated by the estrogen receptor, while in the 3S,4S-enantiomer, this methyl group is projected upward. Thus, we suggest that the bioactive l-enantiomer of centchroman will have the 3R,4R absolute configuration.

Centchroman↗