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Biomedical subjects

S Roy

Publications and source records attributed to S Roy.

At least 91 records · Page 5Linked to original sources
PubMed2002

Mapping of the candidate tumor suppressor genes' loci on human chromosome 3 in head and neck squamous cell carcinoma of an Indian patient population.

The candidate tumor suppressor genes' (TSG) loci on human chromosome 3 (chr.3) were mapped in six dysplastic lesions and 51 primary squamous cell carcinoma from head and neck region of an Indian patient population by using 20 highly polymorphic microsatellite markers. The two chromosomal regions 3p12-13 and 3p21.2-22 have shown the highest losses of heterozygosity (LOHs) of 34.6-38% and 37-46%, respectively with statistically significant clinical correlation's with tobacco habit, positive lymph node and tumor stages. In addition, high frequencies of microsatellite size alterations (MAs) of 16.2-28.5% and 23.8-28.2% were observed in the chromosomal 3p11-13 and 3p21.2-22 regions, respectively, with significant above-mentioned clinical correlation only in the 3p11-13 region. In the dysplastic lesions, the prevalence of LOHs compared to the MAs had indicated that LOHs might be the early events. Five tumors at stage-III/IV seemed to have lost an entire normal copy of chr.3. It was of particular note that 17% (10/57) of the samples showed rare bi-allelic alterations mainly in and around the high LOHs regions. Thus, (1) the gradual increase of LOHs/MAs during progression of the tumor, (2) high frequencies of MAs, (3) rare bi-allelic alterations in and around high LOHs regions and (4) loss of wild type chr.3 in the later stages of tumor development have suggested that such alterations might provide selective growth advantage to the tumors. Also, we propose from our data that the high LOHs regions (3p12-13 and 3p21.2-22) could harbour putative TSG(s), responsible for the development of head and neck squamous cell carcinoma.

Adult↗
PubMed2002

Shifting serotypes, plasmid profile analysis and antimicrobial resistance pattern of shigellae strains isolated from Kolkata, India during 1995-2000.

One hundred and sixty-six shigellae strains, isolated from stool samples of paediatric patients (< 5 years old) at a Childrens' Hospital in Kolkata, India during the period of 1995-2000 were examined for serotyping, drug resistance pattern and plasmid profiles. Sh. flexneri (58 %) was found to be commonest isolate of total shigellae, followed by Sh. sonnei (28 %), Sh. boydii (9%) and Sh. dysenteriae (5%). This profile of species was in sharp contrast to the picture obtained before 1995, when Sh. dysenteriae 1 predominated over Sh. flexneri. In Sh. flexneri strains, Sh. flexneri 2a (35%) was the most prevalent serotype, following Sh. flexneri 3a (31%), Sh. flexneri 6 (14%), Sh. flexneri 2b (11%) and Sh. flexneri 4 (9%). Resistance patterns of the strains to 12 commonly used antimicrobial agents and minimum inhibitory concentrations (MICs) of the antibiotics were also tested. All strains were found uniformly susceptible to norfloxacin, but more than 90% strains were resistant to tetracycline, co-trimoxazole and 67% strains were resistant to ampicillin. Resistance to amoxicillin, chloramphenicol and nalidixic acid was found in 55% (range 45-74%), 46% (range 40-60%) and 29% (range 15-40%) strains respectively. Overall, shigellae strains showed statistically significant increase in resistance against tetracycline, nalidixic acid and furazolidone (P < 0.05) over the years of this study. This indicates decreased efficacy of furazolidone, cotrimoxazole and nalidixic acid for the empirical treatment of shigellosis in Kolkata. Although a few strains showed intermediate susceptibility to ciprofloxacin (4%) and cefotaxime (10%) by disk diffusion test, but the MICs of those antibiotics were within the normal limits. Almost 57% of the strains were resistant to four or more drugs with high MICs of the antibiotics. Plasmid profile analysis revealed presence of large plasmid of 220 kb in majority of the strains except in Sh. sonnei and a correlation between presence of smaller plasmids and shigellae serotypes. Hence this study reports epidemiological change of shigellae species in Kolkata, India with regard to serotypes and antibiotic resistance patterns.

Anti-Bacterial Agents↗
PubMed2002

Exploring relationships between mimic configuration, peptide conformation and biological activity in indolizidin-2-one amino acid analogs of gramicidin S.

Indolizidin-2-one amino acids (I2aas, 6S- and 6R-1) possessing 6S- and 6R-ring-fusion stereochemistry were introduced into the antimicrobial peptide gramicidin S (GS) to explore the relationships between configuration, peptide conformation and biological activity. Solution-phase and solid-phase techniques were used to synthesize three analogs with I2aa residues in place of the d-Phe-Pro residues at the turn regions of GS: [(6S)-I2aa4-5,4'-5']GS (2), [Lys2,2',(6S)-I2aa4-5,4'-5']GS (3) and [(6R)-I2aa4-5,4'-5']GS (4). Although conformational analysis of [I2aa4-5,4'-5']GS analogs 2-4 indicated that both ring-fusion stereoisomers of I2aa gave peptides with CD and NMR spectral data characteristic of GS, the (6S)-I2aa analogs 2 and 3 exhibited more intense CD curve shapes, as well as greater numbers of nonsequential NOE between opposing Val and Leu residues, relative to the (6R)-I2aa analog 4, suggesting a greater propensity for the (6S)-diastereomer to adopt the beta-turn/antiparallel beta-pleated sheet conformation. In measurements of antibacterial and antifungal activity, the (6S)-I2aa analog 2 exhibited significantly better potency than the (6R)-I2aa diastereomer 4. Relative to GS, [(6S)-I2aa4-5,4'-5']GS (2) exhibited usually 1/2 to 1/4 antimicrobial activity as well as 1/4 hemolytic activity. In certain cases, antimicrobial and hemolytic activities of GS were shown to be dissociated through modification at the peptide turn regions with the (6S)-I2aa diastereomer. The synthesis and evaluation of GS analogs 2-4 has furnished new insight into the importance of ring-fusion stereochemistry for turn mimicry by indolizidin-2-one amino acids as well as novel antimicrobial peptides.

Amino Acid Sequence↗
PubMed2002

Oncogenic human papillomavirus (HPV) infection and uterine cervical cancer: a screening strategy in the perspective of rural India.

The predominance of cervical cancer in India can mostly be attributed to the lack of early screening. The objective of the present study has been, therefore, to determine a cost-effective oncogenic human papillomavirus (HPV)-based cervical cancer screening plan for rural Indian women. The results showed that in normal women, highest prevalence of HPV 16/18 infection was in the age group < or =23 years and lowest in > or =44 years with an insignificant change in between. HPV 16/18 infection was significantly associated with cervical erosion at age < or =23 years, but not with cytology or visual inspection with acetic acid testing at any age. The low-grade cytological lesions, however, increased only with increase in age. Fourteen per cent of the cervical malignancy was also found to be present in the age group 24-33 years with an 87% HPV infection. Here we proposed a cost-effective screening scheme in which HPV testing must be performed in women (a) < or =23 years with cervical erosion and (b) 24-43 years, as an adjunct to Pap smears (both HPV and cytology were prevalent in this group). For women > or =44 years, HPV testing might not be useful, since abnormal cytology was more prominent over the viral infection. We infer that by not performing HPV test in the group < or =23 years, approximately 76% of the high-risk HPV-infected individuals potentially "at risk" for developing cervical cancer might be missed.

Acetic Acid↗
PubMed2002

Descemet membrane detachment after nonpenetrating filtering surgery.

PURPOSE: To make surgeons performing nonpenetrating filtering surgery aware of an unusual complication namely Descemet membrane detachment. METHODS: We retrospectively reviewed nine eyes of nine patients seen in our hospital with Descemet membrane detachment occurring after nonpenetrating filtering surgery from January 1994 to December 2000. RESULTS: Both planar and nonplanar detachments were reported. Neither scrolls nor tears in the Descemet membrane were observed in any patient. After viscocanalostomy (four patients), the detachment was generally noticed shortly after the procedure and the cornea maintained its clarity. After deep sclerectomy with a collagen implant (five patients), it developed weeks to months postoperatively with adjacent corneal edema. Four patients had descemetopexy. None required more than one procedure. However, at the last visit, two detachments persisted although they had diminished in size: one after viscocanalostomy and conservative treatment and one after descemetopexy after deep sclerectomy with a collagen implant. To date otherwise, no signs of significant corneal damage could be observed clinically nor by specular microscopy and pachymetry. CONCLUSIONS: The diagnosis of Descemet membrane detachment can be easily overlooked or misdiagnosed. The clinical presentation, clinical course, and pathogenesis depend on the type of nonpenetrating filtering surgery performed. Ophthalmologists should be aware of this unusual complication, which is likely to be more common after nonpenetrating filtering surgery than after trabeculectomy. A period of observation before attempting descemetopexy is recommended.

Adult↗
PubMed2002

Sequential transformation of t(8;13)-related disease: a case report.

We report a case of an atypical myeloproliferative disorder with t(8;13) that presented as B-lineage acute lymphoblastic leukaemia (B-ALL). Following induction chemotherapy, the disease manifested as chronic myeloproliferative state, which responded to hydroxyurea. Terminally, the disease transformed into acute myeloid leukaemia (AML) with additional chromosomal abnormalities including monosomy 7. To our knowledge, this is the first case of this rare atypical myeloproliferative disorder with t(8;13) that presented as B-ALL and terminally transformed to AML with additional chromosomal abnormalities.

Acute Disease↗
PubMed2002

Isolated duodenal metastasis from breast carcinoma.

Small bowel neoplasms comprise 0.1% of all malignancies. Of these one-third are duodenal, mainly primary. Isolated duodenal secondaries arising on account of haematogenous spread is rare. Our case of duodenal obstruction due to an isolated duodenal metastasis as a result of haematogenous spread from breast carcinoma is unique in the literature.

Adult↗
PubMed2001

Conformational properties of alpha-tubulin tail peptide: implications for tail-body interaction.

The carboxy-terminal segments of the alpha/beta-tubulins are flexible regions rich in acidic amino acid residues. It is generally believed that these regions play crucial roles in tubulin polymerization and interaction with many ligands, including colchicine. Exactly how these effects are exerted are not known at present. One such interesting aspect is the pH dependence of colchicine-tubulin interaction and the influence of the alpha-tail on the binding interaction. We have investigated the location of the colchicine-binding site on tubulin by docking. It has been located on the alpha/beta interface on the N-terminal side, which is also supported by much of the solution data. This location is too far from the tail regions, suggesting that influence of the tail region is transmitted by a pH-dependent conformational change. Two-dimensional NMR studies indicate that at pH 7 a 13-residue peptide corresponding to alpha-tubulin tail shows little NOE constraints, suggesting extended conformation. On the contrary, at pH 5, a relatively compact structure was deduced from the interproton NOE constraints. Pulsed field gradient measurement of diffusion constant indicates that the peptide at pH 5 is substantially faster diffusing than at pH 7. The Perrin factors calculated from diffusion data indicates that the peptide structure at pH is significantly more compact than at pH 7. Temperature coefficients of several amide protons at pH 5 fall below 5 ppb/(o)K, indicating a degree of protection. A difference is also seen in the CD spectra obtained at different pHs, consistent with the NMR data. We have investigated the probable spatial organization of the tail of the alpha-subunit of tubulin, in the high pH extended form and the low pH compact form. On the basis of correlation of pH dependence of many properties of tubulin and the conformation of the alpha-tail peptide, we propose that the intrinsic conformational preference of the tail-region modulate the tail-body interaction, which in turn has important bearing on colchicine binding properties.

Binding Sites↗
PubMed2001

Role of Src kinase in diperoxovanadate-mediated activation of phospholipase D in endothelial cells.

We have shown earlier that oxidant-induced activation of phospholipase D (PLD) in vascular endothelial cells (ECs) is regulated by protein tyrosine kinases. To further understand the regulation of oxidant-induced PLD activation, we investigated the role of Src kinase. Treatment of bovine pulmonary artery ECs (BPAECs) with a model oxidant, diperoxovanadate (DPV), at 5 microM concentration, for 30 min, stimulated PLD activity (four- to eightfold), which was attenuated by tyrosine kinase inhibitors and by Src kinase-specific inhibitors PP-1 and PP-2, in a dose- and time-dependent fashion. Furthermore, BPAECs exposed to DPV (5 microM) for 2 min showed activation of Src kinase as observed by increased tyrosine phosphorylation and autophosphorylation in Src immunoprecipitates, which was attenuated by PP-2. Src immunoprecipitates of cell lysates from control BPAECs exhibited PLD activity in cell-free preparations, which was Arf- and Rho-sensitive and was enhanced at 2 min of DPV (5 microM) treatment. Also, Western blots of Src immunoprecipitates of control cells revealed the presence of PLD(1) and PLD(2), suggesting the association of PLD with Src kinase under basal conditions. However, exposure of cells to DPV (5 microM) for 2 min enhanced the association of PLD(2) but not PLD(1) with Src. Western blotting of immunoprecipitates of PLD(1) and PLD(2) isoforms of control BPAECs revealed the presence of Src under basal conditions and exposure of cells to DPV (5 microM) for 2 min enhanced the association of PLD(2) with Src in PLD(2) immunoprecipitates. Transient expression of a dominant negative mutant of Src in BPAECs attenuated DPV- but not TPA-induced PLD activation. In cell-free preparations, Src did not phosphorylate either PLD(1) or PLD(2) compared to protein kinase Calpha or p38 mitogen-activated protein kinase. These data show for the first time a direct association of Src with PLD in ECs and regulation of PLD in intact cells.

Animals↗
PubMed2001

A "master" in base unpairing during isomerization of a promoter upon RNA polymerase binding.

Isomerization of a closed to open complex of a promoter upon RNA polymerase binding involves base unpairing at the -10 region. After potassium permanganate sensitivity of unpaired thymine residues, we studied base unpairing at the -10 region during isomerization upon RNA polymerase binding at the P1 and P3 promoters of the gal operon. Substitution of adenine by 2-amino purine (2-AP) at the invariable A small middle dotT base pair at the -11 position of P1 and P3 prevented unpairing not only at that position but also at the other downstream positions, suggesting a "master" role of the adenine base at -11 of the template strand in overall base unpairing. 2-AP at -11 did not inhibit the formation of RNA polymerase small middle dotpromoter complex and subsequent isomerization of the polymerase. Substitution of adenine by 2-AP at several other positions did not affect thymine unpairing. Changing the position of the amino group from C6 in adenine to C2 in 2-AP is mutational only at the master switch position, -11.

Base Pairing↗
PubMed2001

A Pb isotope and trace element study of rainwater from the Massif Central (France).

Lead isotope ratios and Zn, Pb, Cu, Cd, Sb and Rb contents were measured in samples of rainwater collected over a period of 15 months from the Massif Central (France). Each sample, collected automatically at monthly intervals, represents a series of rainfall events. Rainwater chemistry was interpreted in terms of the chemical contributions from wet deposition and from different source regions for dust in the centre of France. Trace element concentrations in rainwater samples showed a wide range, particularly for Pb (1.30-465 microg/l), with variations decreasing for Cd (0.07-1.70 microg/l), Zn (1.00-54.00 microg/l), Cu (0.20-25.00 microg/l), Sb (approximately 0-0.33 microg/l) and Ni (approximately 0-15.00 microg/l). Trace element contents do not correlate with rainfall amount and no inter-element correlations are evident in the data. Lead is the most common trace metal found in the rainwater (mean value = 996 microg/m2/y) while Sb is the least common element measured (mean value = 1.12 microg/m2/y). The composition of rainwater collected from the Massif Central shows a range in Pb isotope ratios from 17.935 to 19.22 (206Pb/204Pb), 15.578 to 15.73 (207Pb/204Pb) and 37.559 to 38.606 (208Pb/204Pb). A five-component mixing model involving contributions from the natural background, gasoline inputs from industrial and agricultural activity and a source resulting from mining waste may be used to explain both the Pb isotope signature and the fluctuations in trace metal contents of Massif Central rainwater.

Agriculture↗
PubMed2001

Caspase 3 deficiency rescues peripheral nervous system defect in retinoblastoma nullizygous mice.

The retinoblastoma tumor suppressor protein, pRb, is a key regulator of cell cycle and has been implicated in the terminal differentiation of neuronal cells. Mice nullizygous for pRb die by embryonic day 14.5 from hematopoietic and neurological defects attributed to failed differentiation (Clarke et al., 1992; Jacks et al., 1992; Lee et al., 1992). Previous studies by MacLeod et al. (1996) have demonstrated that the loss of p53 protects Rb-deficient CNS neurons but not peripheral nervous system (PNS) neurons from cell death. Thus, the mechanisms by which PNS neurons undergo apoptosis in response to Rb deficiency remain unknown. In view of the pivotal role of caspase 3 in the regulation of neuronal apoptosis during development, we examined its function in the execution of the wide-spread neuronal cell death induced by Rb deficiency. Our results support a number of conclusions. First, we show that caspase 3 becomes activated in all neuronal populations undergoing apoptosis. Second, caspase 3 deficiency does not extend the life span of Rb null embryos, because double null mutants exhibit high rates of liver apoptosis resulting in erythropoietic failure. Third, Rb/caspase 3 double-mutant neurons of the CNS exhibit widespread apoptosis similar to that seen in Rb mutants alone; thus caspase 3 deficiency does not protect this population from apoptosis. Finally, in contrast to the CNS, neurons of the PNS including those comprising the trigeminal ganglia and the dorsal root ganglia are protected from apoptosis in Rb/caspase 3 double-mutant embryos. Examination of the mechanistic differences between these two cell types suggest that CNS neurons may invoke other caspases to facilitate apoptosis in the absence of caspase 3. These findings suggest that PNS neurons are dependent on caspase 3 for the execution of apoptosis and that caspase 3 may serve as a key therapeutic target for neuroprotection after injury of this cell type.

Amyloid beta-Protein Precursor↗
PubMed2001

Hedgehog signaling pathway is essential for pancreas specification in the zebrafish embryo.

Recent studies have implicated the signaling factor Sonic hedgehog (Shh) as a negative regulator of pancreatic development, but as a positive regulator of pancreas function in amniotes [1-4]. Here, using genetic analysis, we show that specification of the pancreas in the teleost embryo requires the activity of Hh proteins. Zebrafish embryos compromised in Hh signaling exhibit disruption in the expression of the pancreas-specifying homeobox gene pdx-1 and concomitantly show almost complete absence of the endocrine pancreas. Reciprocally, ubiquitous activation of the Hh pathway in wild-type embryos causes ectopic induction of endodermal pdx-1 expression and the differentiation of supernumerary endocrine cells. Our results suggest that Hh proteins influence pancreas specification via inductive interactions from the axial midline rather than through their localized expression in the endodermal cells themselves.

Animals↗
PubMed2001

Photoprotection and long-term acclimation to UV radiation in the marine diatom Thalassiosira weissflogii.

Unialgal cultures of the marine diatom Thalassiosira weissflogii (Grunow) were exposed for 40 days to artificial UV-B radiation in the presence of PAR and UV-A to examine long-term acclimation to UV, PAR and UV-A were supplied 14 h daily, while UV-B (two levels: 0.16 and 0.30 W m(-2) unweighted) was supplied for 4 h/day. Growth rates and photochemical capacity (CFC ratio) both decreased over the first 10-15 days, then recovered. No obvious differences were noted between the responses to the two UV-B treatments. The concentration of the major pigments (chlorophyll a and c(1+2), fucoxanthin and beta,beta-carotene) changed very little with time, except for diatoxanthin. which increased over the first 16 days, decreased over the next 13 days, then increased again from day 29 to the end of the experiment. The concentration of total mycosporine-like amino acids (MAAs) was initially undetectable, then increased from day 16 in the high UV-B treatment and after day 22 in the low UV-B treatment, reaching a maximum on day 29 for both treatments and decreasing afterwards. The synthesis of MAAs proceeded only once photochemical capacity had recovered from the initial UV stress and this recovery likely involved the xanthophyll cycle (diatoxanthin increase). The concentration of MAAs decreased when the cells showed signs of photoinhibition (decrease in CFC ratio). It also showed an inverse trend with diatoxanthin. UV-B alone had little regulatory effect over these responses, except possibly for an earlier synthesis of MAAs under HUV-B conditions. This suggests that the observed changes were due to UV-A rather than to UV-B exposure. The overall response of this coastal diatom to prolonged UV exposure indicates that T. weissflogii is a relatively UV-tolerant species and that its long-term response to UV exposure involves an activation of the xanthophyll cycle followed by the synthesis of MAAs, which may proceed only when photoinhibition is relieved.

Acclimatization↗
PubMed2001

Role of the carboxy-termini of tubulin on its chaperone-like activity.

Mutational analysis and the enzymatic digestion of many chaperones indicate the importance of both hydrophobic and hydrophilic residues for their unique property. Thus, the chaperone activity of alpha-crystallin is lost due to the substitution of hydrophobic residues or upon enzymatic digestion of the negatively charged residues. Tubulin, an eukaryotic cytoskeletal protein, exhibits chaperone-like activity as demonstrated by prevention of DTT-induced aggregation of insulin, thermal aggregation of alcohol dehydrogenase, betagamma-crystallin, and other proteins. We have shown that the tubulin lost its chaperone-like activity upon digestion of its negatively charged C-termini. In this article, the role of the C-terminus of individual subunits has been investigated. We observe that the digestion of C-terminus of beta-subunit with subtilisin causes loss of chaperone-like activity of tubulin. The contribution of C-terminus of alpha-subunit is difficult to establish directly as subtilisin cleaves C-terminus of beta-subunit first. This has been ascertained indirectly using a 14-residue peptide P2 having the sequence corresponding to a conserved region of MHC class I molecules and that binds tightly to the C-terminus of alpha-subunit. We have shown that the binding of P2 peptide to alphabeta-tubulin causes complete loss of its chaperone-like activity. NMR and gel-electrophoresis studies indicate that the P2 peptide has a significant higher binding affinity for the C-terminus of alpha-subunit compared to that of beta-subunit. Thus, we conclude that both the C-termini are necessary for the chaperone-like activity of tubulin. Implications for the chaperone functions in vivo have been discussed.

Amino Acid Sequence↗