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Biomedical subjects

S Basu

Publications and source records attributed to S Basu.

At least 127 records · Page 7Linked to original sources
PubMed1999

Functional deficiencies of peritoneal cells from gene-targeted mice lacking G-CSF or GM-CSF.

Gene-targeted mice lacking the hemopoietic growth factors, granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage (GM)-CSF, show increased susceptibility to infection with the facultative intracellular bacterium, Listeria monocytogenes. The resident peritoneal cell populations from G-CSF(-/-) and GM-CSF(-/-) mice showed reduced production of the bactericidal molecule nitric oxide. Macrophage-mediated tumoricidal activity and phagocytosis of Listeria were reduced in G-CSF(-/-), but not in GM-CSF(-/-), mice. In G-CSF(-/-) mice, there was an unexpected expansion (from 18% in WT to 38%) of a population of cells with morphology intermediate between typical macrophages and typical lymphocytes. These cells had some of the features of poorly differentiated macrophages, being adherent to plastic but poorly phagocytic, nonspecific esterase positive but myeloperoxidase negative. They were largely negative for the macrophage marker F4/80 and for Thy1, B220, and Gr1. Their disproportionate presence, and the corresponding deficiency in typical macrophages, possibly accounts for some of the functional deficiencies observed in G-CSF(-/-) mice.

Animals↗
PubMed1999

The role of neoadjuvant and adjuvant chemotherapy regimens consisting of different combinations of drugs in the treatment of advanced oral cancer.

We performed a retrospective analysis on the effect of neoadjuvant chemotherapy with three cycles of methotrexate (100 mg/m2 on day 1), cisplatin (90 mg/m2 on day 1) and bleomycin (20mg/m2 on day 1-5) with 21 d gap between each cycle in 44 patients with advanced squamous cell carcinoma of the cheek, lip and tongue followed by surgery and adjuvant chemotherapy consisting of cisplatin (90 mg/m2 on day 1), Mitomycin C (6 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 120 h continuous infusion from day 1) repeated every 3 weeks for three cycles. Following induction chemotherapy, complete response was observed in 11 out of 44 patients (25%), and a partial response in a further 28 patients (64%). The overall median survival of all patients was 29 months and those in stage III and stage IV were 30 and 15 months respectively (P< 0.001). The median duration of the time to relapse in patients who responded to adjuvant chemotherapy was 28 months. The main toxic effect was vomiting followed by hematological toxicity. No treatment-related deaths occurred. The regimen showed a significant response, encouraging median survival and a good tolerability profile.

Adult↗
PubMed1999

Green tea extract decreases plasma malondialdehyde concentration but does not affect other indicators of oxidative stress, nitric oxide production, or hemostatic factors during a high-linoleic acid diet in healthy females.

BACKGROUND: Green tea contains polyphenolic catechins which can act as antioxidants and thus decrease the risk for cardiovascular diseases. AIM OF THE STUDY: To investigate whether green tea extract differs from placebo in its effects on markers of antioxidant status, lipid peroxidation, nitric oxide production, thromboxane production, and blood coagulation during a controlled high linoleic acid diet in healthy subjects. METHODS: Twenty healthy non-smoking females (23-50 years) participated in a 4-week controlled intervention study. The experimental diet was rich in linoleic acid (9 en%) and contained fat, protein, and carbohydrates: 27, 14, and 59 en%, respectively. In addition, the subjects ingested encapsulated green tea extract (3 g/d) or placebo mixture in a double-blind manner. Fasting blood samples and five 24-hour urines were collected before and at the end of the 4-week experimental period. Same samples were received from 10 control subjects. RESULTS: Green tea extract significantly decreased plasma malondialdehyde (MDA) concentration in comparison with the placebo treatment. The treatments did not differ in serum lipids, indicators of antioxidant status, urinary 8-isoprostaglandin F2 alpha, 2,3-dinorthromboxane B2, nitric oxide metabolites or coagulation indicators. CONCLUSIONS: We conclude that an amount of green tea extract which corresponds to 10 cups of tea per day for 4 weeks does not have specific effects on several indicators related to risk of cardiovascular diseases in comparison with placebo treatment. The relatively small but significant decrease in lipid peroxidation indicated by decreased plasma MDA was not associated with changes in markers of oxidative stress (urinary 8-isoprostaglandin F2 alpha and blood oxidized glutathione) or hemostasis.

Adult↗
PubMed1999

Carvedilol prevents remodeling in patients with left ventricular dysfunction after acute myocardial infarction.

OBJECTIVE: The aim of the study was to assess the effects of carvedilol, a vasodilating nonselective beta-blocker, on the indexes of left ventricular remodeling after acute myocardial infarction in those with left ventricular dysfunction. METHODS AND RESULTS: Forty-nine patients with predischarge left ventricular ejection fraction <45% after acute myocardial infarction were evaluated in a double-blind, randomized, placebo-controlled, parallel group study (selected from the database of the Carvedilol Heart Attack Pilot Study: CHAPS). Patients received medication after thrombolysis and continued to do so for 6 months. Two-dimensional echocardiography was performed before discharge (7 to 10 days after admission) and at 3 months after acute myocardial infarction. Analysis of variance showed that wall thickness opposite the site of infarction decreased from (mean +/- SD) 12.3 +/- 2.1 mm to 11.0 +/- 2.4 mm with carvedilol compared with 11.6 +/- 1.9 mm to 12.2 +/- 1.9 mm with placebo (P =.01). Left ventricular mass changed from 235 +/- 74 g to 217 +/- 64 g with carvedilol compared with 227 +/- 80 g to 252 +/- 85 g with placebo ( P =.02). Carvedilol prevented alteration of sphericity index (ratio of long and short axis of left ventricle) that changed from 1.65 +/- 0.29 to 1.66 +/- 20 with carvedilol compared with 1.58 +/- 0.33 to 1.39 +/- 0.19 with placebo (P =.02); alteration was also prevented of wall thickening abnormality at infarct site, which changed from 9.2 +/- 3.1 cm2 to 9.1 +/- 3.5 cm 2 with carvedilol compared with 10.3 +/- 3.3 cm2 to 13.5 +/- 4.6 cm2 with placebo (P =.002). CONCLUSION: Carvedilol administered early after acute myocardial infarction results in attenuation of left ventricular remodeling in patients with persistent left ventricular dysfunction before discharge.

Adrenergic beta-Antagonists↗
PubMed1999

Thiophilic metal ion rescue of phosphorothioate interference within the Tetrahymena ribozyme P4-P6 domain.

Divalent metal ions are essential for the folding and catalytic activities of many RNAs. A commonly employed biochemical technique to identify metal-binding sites in RNA is the rescue of Rp alpha-phosphorothioate (PS) interference by the addition of soft divalent metal ions. To access the ability of such experiments to accurately identify metal-ion coordinations within a complex RNA fold, we report metal-rescue results from the Tetrahymena group I intron P4-P6 domain, where the location and coordination of five divalent metal ions have been determined by X-ray crystallography [J.H. Cate et al., Nat Struct Biol, 1997, 4:553]. We used a native gel mobility-shift to assay for P4-P6 folding in the presence of various divalent metal ions, and found that even moderate concentrations of Mn2+ (> or =0.5 mM) can rescue PS interference at sites that do not coordinate metal ions within the P4-P6 crystal structure. To control for such effects, 2'-deoxynucleotide interference was used to titrate the Mn2+ concentration to a level that produces metal-ion-specific rescue (0.3 mM). This concentration of Mn2+ specifically rescued four of the six metal-dependent phosphorothioate effects within the RNA domain, including PS interference resulting from outer-sphere coordination to the metals. Both sites that were not specifically rescued make inner-sphere metal-ion coordinations. Cd2+ and Zn2+ afforded rescue at a smaller subset of the six metal-specific PS sites, though again phosphates making outer-sphere coordinations to metal ions were rescued preferentially. These data on P4-P6 domain folding reinforce the need for caution when interpreting metal-rescue experiments.

Animals↗
PubMed1999

Ceramide glycanase activities in human cancer cells.

Ceramide glycanase (CGase) activities have been detected in different human tumor cells (colon, carcinoma Colo-205; neuroblastoma, IMR-32; breast cancer lines, SKBr3 and MCF7). However, the level of enzymatic activity is lower in these cells compared to that present in other mammalian tissues reported before (Basu, M., Kelly, P., Girzadas, M. A., Li, Z., and Basu, S. Methods Enzymol. (in press)). The majority of CGase activity was found in the 100,000 g soluble supernatant fraction isolated from all these cell lines and tissues. Using the soluble enzyme, the requirement for optimum CGase activity was found to be consistent with previous observations found for rat and rabbit tissues (Basu, M., Dastgheib, S., Girzadas, M. A., O'Donnell, P. H., Westervelt, C. W., Li, Z., Inokuchi, J. I., and Basu, S. (1998) Acta Pol. Biochim. 42:327). The CGase activities from both Colo-205 and IMR-32 cells are optimum at a protein to detergent ratio of one. All the mammalian CGases, including human cancer cells, show an optimum pH between 5.5 and 5.8 in sodium acetate buffer. The CGase activities from cancer cells are found to be cation-independent; however, mercury, zinc, and copper ions seem to inhibit the enzyme activity substantially in both tumor cells lines. The mercury ion inhibition of CGase activities from all different sources indicates a possible structural homology in the CGase proteins. Radiolabeled substrates, labeled at the sphingosine double bond or at the 3-position of sphingosine without modifying double bond of sphingosine were used in this investigation. Both were active substrates with all enzyme preparations isolated from different cancer cells (apparent Km, 500 microM for nLcOse5[3H-DT]Cer and 350 microM for GgOse4[sph-3-3H]Cer with Colo-205 enzyme). Structural analogues of ceramide and sphingosine (L-PPMP. L-PDMP, alkylamines, and Tamoxifen) inhibited cancer cell CGase activities in vitro.

Antineoplastic Agents↗
PubMed1999

DNA polymerase-associated lectin (DPAL) and its binding to the galactose-containing glycoconjugate of the replication complex.

The highly purified DNA Pol-alpha from rat prostate tumor (PA-3) and human neuroblastoma (IMR-32) cells appeared to be inhibited by Ricin (RCA-II), and Con-A. Loss of activity (40 to 60%) of a specific form of DNA polymerase from IMR-32 was observed when the cells were treated with tunicamycin [Bhattacharya, P. and Basu, S. (1982) Proc. Natl. Acad. Sci., USA 79:1488-1492]. Binding of ConA and RCA to human recombinant DNA polymerase-alpha showed a specific labile site in the N-terminus [Hsi et al.. (1990) Nucleic Acid Res. 18:6231-6237]. The catalytic polypeptide, DNA polymerase-alpha of eukaryotic origin, was isolated from developing tissues or cultured cells as a family of 180 to 120 kDa polypeptides, perhaps derived from a single primary structure. Immunoblot analysis with a monoclonal antibody (SJK-237-71) indicated that the lower molecular weight polypeptides resulted from either proteolytic cleavage of post-translational modification after specific cleavages. Present results suggest DNA polymerase-alpha from embryonic chicken brain (ECB) contains an alpha-galactose-binding subunit which may be involved in developmental regulation of the enzyme. It was shown before that the catalytic subunit of DNA polymerase-alpha reduces from 186 kDa in 11-day-old ECB to 120 kDa in 19-day-old ECB [Ray, S. et al. Cell Growth and Differentiation 2:567-573] by the treatment with methyl-alpha-galactose. The low molecular weight DNA polymerase activity (120 kDa) can be reconstituted to high molecular weight (Mr = 186 kDa) with an alpha-galactose binding, 56kDa lectin-like protein. Polyclonal antibodies raised against the purified lectin were able to precipitate DNA. Pol-alpha as determined by immunostaining with the polymerase-alpha-specific monoclonal antibody SJK 132-20, suggesting this is a DNA polymerase associated-lectin (DPAL). RCA-II and GS-I-Sepharose 4B chromatographies resulted in significant purification of DNA-alpha and a complete separation of polymerase complex and primase.

Animals↗
PubMed1999

Decreased dopamine receptor expression and its second-messenger cAMP in malignant human colon tissue.

As an important enteric neurotransmitter, the role of dopamine as a mitotic inhibitor as well as a protective factor of epithelial cells of stomach and colon indicates its significance in malignant growth of gastrointestinal tract. Our previous results have shown significant alteration of dopamine receptors in human malignant stomach tissues. The present experiments, therefore, evaluate DA content, its receptor expression, and its second-messenger cAMP in human malignant colon tissues to evaluate its role. Results demonstrate a significant decrease of dopamine content, its receptor expression, and its second-messenger cAMP in malignant tissues of human colon. These results may provide insight into the role of dopamine as an enteric neurotransmitter on malignant growth of human colon and may also suggest a therapeutic approach targeting dopamine receptors and its signal transduction.

Adenocarcinoma↗
PubMed1999

Regulation of VH gene repertoire and somatic mutation in germinal centre B cells by passively administered antibody.

Immunization with T-dependent antigens induces a rapid differentiation of B cells to plasmacytes that produce the primary immunoglobulin M (IgM) and IgG antibodies with low affinities for the immunogen. It is proposed that the IgG antibody forms immune complexes with the residual antigen which provide an important stimulus for the formation of germinal centres (GC) and the activation of somatic mutation. This hypothesis was tested by passive administration of hapten-specific antibody into mice shortly after the immunization with nitrophenyl (NP) coupled to chicken gamma globulin (NP-CGG) in an environment of limited T-cell help. Athymic mice that received normal T helper cells at 72 hr after the administration of antigen produced low levels of anti-NP antibody and the splenic GC formation was delayed until day 12 after the antigen administration. The analysis of VDJ segments from NP-reactive GC B cells showed very few mutations in the VH genes. Passive injection of anti-NP IgG1 monoclonal antibody - but, not IgM - stimulated the GC formation up to normal levels and the somatic mutation activity in the GC B cells was fully restored. In addition, GC B cells in the recipients of IgG1 antibody demonstrated a change in the usage of germline-encoded VH genes which was not apparent among the primary antibody-forming cells. These results suggest the existence of a specific feedback mechanism whereby the IgG antibody regulates the GC formation, clonotypic repertoire and somatic mutation in GC B cells.

Animals↗
PubMed1999

Painless osteoid osteoma in a metacarpal.

Osteoid osteoma is a benign primary tumour of bone occurring in the first two decades of life. It presents with pain and is uncommon in the hand, particularly so in the metacarpals. We report a painless osteoid osteoma affecting a metacarpal.

Adolescent↗
PubMed1999

F2-isoprostane excretion rate and diurnal variation in human urine.

8-Iso-PGF2alpha is formed in vivo by non-enzymatic free radical catalysed oxidation of arachidonic acid. Urinary measurement of this compound has previously been shown to reflect the oxidative stress of the body in human and animal studies. To investigate the normal excretion rate and a possible diurnal variation of 8-iso-PGF2alpha excretion in humans urinary samples were collected from ten healthy volunteers of both sexes at different times during a day and as a 24-h urine sample. The samples were analyzed by a newly developed radioimmunoassay with a specific antibody against free 8-iso-PGF2alpha. There was no diurnal variation in the urinary levels of 8-iso-PGF2alpha during the day in this study. Neither was there any statistically significant difference between the 8-iso-PGF2alpha levels at any time of the day or in the morning urine samples compared to the 24-h urine samples. In conclusion, all urine samples collected at any time of the day, preferably a morning urine sample (representative urine from 6-8 hours), can thus be used to obtain a reliable and adequate value of the amount of the 8-iso-PGF2alpha excretion in urine in healthy individuals.

Adult↗
PubMed1999

NMR structures of a nonapeptide from DNA binding domain of human polymerase-alpha determined by iterative complete-relaxation-matrix approach.

Nuclear magnetic resonance structures of a nonapeptide, ERFKCPCPT, selected from the DNA binding domain of human polymerase-alpha, were determined by complete relaxation matrix analysis of transverse NOE data. The structures exhibit a type III turn with residues KCPC, and the remaining residues exhibit non-ordered structures. The turn was confirmed by alpha, N (i,i+3) connectivity, a low temperature coefficient of NH chemical shift (-3.1 x 10(-3)) of the fourth residue, 3J(NHalpha) coupling constants, and characteristic CD peaks at 228 and 200 nm. Furthermore, phi and psi dihedral angles for the i + 1, and i + 2 residues of the turn are found to be -80 and -41 and -60 and -40 degrees. The first proline residue is trans- while the second exists in both cis- and trans- configurations, with trans- being more than 80% populated. The trans-configuration was established from C5alpha-P6alpha correlation and phi and psi angles of the proline. The five-membered proline ring is in DOWN puckered (C-beta-exo/C-gamma-endo) conformation. The structure of the peptide reveals that the two cysteine thiols are approximately 5 A(o) apart and appropriately positioned to covalently bind cis-diamminedichloroplatinum(II), a widely used anti-cancer drug.

Circular Dichroism↗
PubMed1999

Bias-corrected confidence intervals for the concentration parameter in a dilution assay.

Interval estimates of the concentration of target entities from a serial dilution assay are usually based on the maximum likelihood estimator. The distribution of the maximum likelihood estimator is skewed to the right and is positively biased. This bias results in interval estimates that either provide inadequate coverage relative to the nominal level or yield excessively long intervals. Confidence intervals based on both log transformation and bias reduction are proposed and are shown through simulations to provide appropriate coverage with shorter widths than the commonly used intervals in a variety of designs. An application to feline AIDS research, which motivated this work, is also presented.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Sledging related spinal injuries and fracture patterns: a report on five cases.

The cases are reported of five patients who presented to The Queens Medical Centre, Nottingham after a sledging accident. All five patients presented consecutively during the first weekend in 1997 having sustained the accident in the same public park. The mechanism and subsequent fracture type is described for each. These injuries are preventable, and increasing public awareness of the risk of sledging in public places may reduce the incidence.

Adolescent↗
PubMed1999

Tumor suppressor protein WT1 inhibits autonomous DNA replication directly, as well as indirectly by causing loss of replicated DNA as a consequence of cell death induced by the protein.

The effects of the Wilms' tumor suppressor protein WT1 on autonomous DNA replication under stable transfection conditions were investigated. COS ts2 monkey kidney cells, which express the simian virus 40 (SV40) replication initiator protein large tumor antigen (TAg) as a temperature-sensitive protein, were stably transfected with SV40 origin-containing plasmids expressing WT1 from the Zn2+ and Cd2+-inducible metallothionein promoter. Stable transformant clones of cells containing the integrated plasmids were isolated at the non-permissive temperature, expanded, and shifted to the permissive temperature to allow autonomous replication of the plasmid and overexpression of WT1. Expression of WT1 triggered apoptosis of the cells. Analysis of the kinetics of occurrence of cell death and accumulation of the replicated plasmid indicated that WT1 inhibited replication directly, and also indirectly by causing loss of replicated plasmid as a consequence of WT1-induced cell death.

Animals↗
PubMed1999

Effect of high arsenic content in drinking water on rat brain.

The permissible limit of arsenic content in drinking water is 0.05 ppm, whereas, in many parts of West Bengal the arsenic level in drinking water is 0.1 ppm, frequently 0.3 ppm and even 3.0 ppm, though rarely. In order to assess possible risk to brain function by drinking such water, rats were given arsenic mixed in drinking water at the above four concentrations for 40 days. There was increased lipid peroxidation at all doses of arsenic, including the 'permissible limit', decrease in glutathione level, superoxide dismutase and glutathione reductase activities, indicating the free-radical-mediated degeneration of brain.

Animals↗