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Biomedical subjects

S Bose

Publications and source records attributed to S Bose.

At least 91 records · Page 5Linked to original sources
PubMed1997

Eccrine sweat gland carcinoma of the scrotum with associated extramammary Paget's disease.

Sweat gland carcinomas are rare tumors which have not previously been reported as arising from the scrotum. We present the first known case of primary eccrine sweat gland carcinoma of the scrotum in association with extramammary Paget's disease (EPD) and review the presentation and management of these tumors. Sweat gland carcinomas frequently coexist with EPD and this association provides insight into the histogenesis of EPD, which is presently unknown. Sweat gland carcinoma should be included in the differential diagnosis of cutaneous scrotal tumors and carefully ruled out pathologically if the diagnosis of EPD alone is made.

Adenocarcinoma↗
PubMed1997

Specific binding of inorganic mercury to Na(+)-K(+)-ATPase in rat liver plasma membrane and signal transduction.

Specific binding of Hg2+ to ouabain-sensitive Na(+)-K(+)-ATPase of rat liver plasma membrane was demonstrated with a Ka of 2.64 x 10(9) and Bmax of 1.6 nmole mg-1 protein. The binding of mercury to the enzyme also causes significant inhibition of the enzyme, which is greater than its ouabain sensitivity. In the cytosol Hg2+ binding to reduced glutathione (GSH) is stimulated by GSH-S-transferase (GST), the activity of which was found to be significantly enhanced by 15 mM Na+ and 10 mM Hg2+. It is proposed that the transport of Hg2+ inside the cell takes place by increased dissociation of Hg2+ from the membrane due to greater avidity of Hg2+ towards cytosolar GSH binding. The GSH-Hg complex enters the nucleus where it dissociates to bind the metal response element (MRE) of the metallothionein (MT) gene to induce MT transcription.

Animals↗
PubMed1997

Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome.

Cowden disease (CD) is an autosomal dominant cancer predisposition syndrome associated with an elevated risk for tumours of the breast, thyroid and skin. Lhermitte-Duclos disease (LDD) cosegregates with a subset of CD families and is associated with macrocephaly, ataxia and dysplastic cerebellar gangliocytomatosis. The common feature of these diseases is a predisposition to hamartomas, benign tumours containing differentiated but disorganized cells indigenous to the tissue of origin. Linkage analysis has determined that a single locus within chromosome 10q23 is likely to be responsible for both of these diseases. A candidate tumour suppressor gene (PTEN) within this region is mutated in sporadic brain, breast and prostate cancer. Another group has independently isolated the same gene, termed MMAC1, and also found somatic mutations throughout the gene in advanced sporadic cancers. Mutational analysis of PTEN in CD kindreds has identified germline mutations in four of five families. We found nonsense and missense mutations that are predicted to disrupt the protein tyrosine/dual-specificity phosphatase domain of this gene. Thus, PTEN appears to behave as a tumour suppressor gene in the germline. Our data also imply that PTEN may play a role in organizing the relationship of different cell types within an organ during development.

Breast Neoplasms↗
PubMed1997

Lymphoid blast crisis during complete cytogenetic remission following interferon-alpha and hydroxyurea therapy.

Chronic myelogenous leukemia (CML) is a clonal disorder starting with a chronic phase and progressing to an acute blastic phase. Philadelphia (Ph) chromosome formation results in the relocation of the ABL oncogene from the chromosome 9q34 to BCR region on 22q11, forming the BCR/ABL fusion gene. The Ph chromosome once detected rarely disappears, except as a result of therapy. We present an unusual Ph-positive CML case, which developed lymphoid blast crisis in complete cytogenetic remission following interferon-alpha and hydroxyurea therapy. Sequential cytogenetic investigations were carried out on bone marrow. After a standard Ph translocation seen at diagnosis, from the 8th month of therapy all metaphases showed a normal diploid karyotype. Fluorescence in situ hybridization detected residual BCR/ABL-positive interphase cells during the 12th month of therapy. In the 14th month, the patient showed 27% blasts in marrow though normal cytogenetics was maintained. Present findings suggest blastic transformation occurred in a Ph-negative lymphoid clone. This supports the hypothesis that an actual leukemogenic event occurs in a multipotent stem cell prior to the acquisition of Ph translocation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Chaperone function of Hsp90-associated proteins.

The Hsp90 heat shock protein of eukaryotic cells regulates the activity of proteins involved in signal transduction pathways and may direct intracellular protein folding in general. Hsp90 performs at least part of its function in a complex with a specific set of partner proteins that include members of the prolyl isomerase family. The properties of the major components of the Hsp90 complex were examined through the use of in vitro protein folding assays. Two of the components, FKBP52 and p23, functioned as mechanistically distinct molecular chaperones. These results suggest the existence of a super-chaperone complex in the cytosol of eukaryotic cells.

Amino Acid Isomerases↗
PubMed1996

Control of the integral membrane proton pump, bacteriorhodopsin, by purple membrane lipids of Halobacterium halobium.

Brief exposure of purple membrane (PM) to dilute Triton X-100 eliminates the actinic light effect on the relative amounts of fast M (Mf) and slow M (Ms) intermediates and alters the character and kinetics of the photocycle, without destroying the native BR trimers (Mukhopadhyay et al., 1994). Particular membrane lipids are removed during the Triton treatment, and adding back an extract of membrane lipids can repair most of the affected photocycle behavior (Dracheva et al., 1996). This paper defines conditions which are important in the reconstitution procedure, using a group of quantitative parameters which measure the extents of damage and repair. Circular dichroism in both the UV and visible ranges shows that Triton can disturb both the secondary structure of BR and its ability to polymerize into trimers. Whereas the damage to protein conformation could be reversed by lipids alone, the formation of trimers and recovery of normal photocycle behavior required both lipids and a high salt concentration.

Bacteriorhodopsins↗
PubMed1996

Dimerization of transcobalamin II receptor. Requirement of a structurally ordered lipid bilayer.

Transcobalamin II receptor (TC II-R) exists as a monomer and a dimer of molecular masses of 62 and 124 kDa in the microsomal and plasma membranes, respectively, and in vitro, pure TC II-R monomer dimerizes upon insertion into egg PC/cholesterol (molar ratio, 4:1) liposomes (Bose, S., Seetharam, S., and Seetharam, B. (1995) J. Biol Chem. 270, 8152-8157 and Bose, S., Seetharam, S., Hammond, T., and Seetharam, B. (1995) Biochem. J. 310, 923-929). The current studies were carried out to define the mechanism of TC II-R dimerization. Both the mature TC II-R (62 kDa) and the enzymatically deglycosylated TC II-R (45-47 kDa) demonstrated optimal association and formed dimers of molecular masses of 95 and 124 kDa, respectively, at 22 degrees C when bound to egg PC vesicles containing at least 10 mol % of cholesterol. Mature TC II-R dimerized upon insertion into synthetic phosphatidylcholine vesicles of different fatty acyl chain length (dimyristoyl, dipalmitoyl, and disteroyl phosphatidylcholine) in the absence or the presence of cholesterol at temperatures below or above their transition temperatures, respectively. Dimerization of TC II-R also occurred with vesicles prepared using lipid extract from the plasma but not microsomal membranes. Cholesterol depletion of native intestinal plasma membranes or its enrichment in the microsomal membranes resulted in the in situ conversion of the 124-kDa dimer to the 62-kDa monomer or of the monomer into the dimer form, respectively. Treatment of plasma membranes with phospholipase A2 resulted in the conversion of the dimer form of the receptor to the monomer form and spin label studies using 1-palmitoyl, 12 doxylsteroyl phosphatidylcholine revealed that interactions of TC II-R with PC vesicles increased order around the probe. Based on these results we suggest that dimerization of TC II-R is mediated by its interactions with a rigid more ordered lipid bilayer membrane, is regulated in plasma membranes by cholesterol levels, and is independent of glycosylation-mediated folding.

Animals↗
PubMed1996

Assessment of the ATP binding properties of Hsp90.

Hsp90, one of the most prominent proteins in eucaryotic cells under physiological and stress conditions, chaperones protein folding reactions in an ATP-independent way. Surprisingly, ATP binding and ATPase activity of Hsp90 has been reported by several groups. To clarify this important issue, we have reinvestigated the potential ATP binding properties and ATPase activity of highly purified Hsp90 using a number of different techniques. Hsp90 was compared to the well characterized ATP-binding chaperone Hsc70 and to two control proteins, immunoglobulin G and bovine serum albumin, that are known to not bind ATP. Hsp90 behaved very similarly to the non-ATP-binding proteins and very differently from the ATP-binding protein Hsc70. Like bovine serum albumin and immunoglobulin G, Hsp90 (i) did not bind to immobilized ATP, (ii) could not be specifically photocross-linked with azido-ATP, (iii) failed to exhibit significant changes in intrinsic protein fluorescence upon ATP addition, and (iv) did not bind to three fluorescent ADP analogues. In contrast, Hsc70 strongly bound ATP and ADP, specifically cross-linked with azido-ATP, and exhibited major shifts in fluorescence upon addition of ATP. Finally, reexamination of the amino acid sequence of Hsp90 failed to reveal any significant homologies to known ATP-binding motifs. Taken together, we conclude that highly purified Hsp90 does not bind ATP. Weak ATPase activities associated with Hsp90 preparations may be due to minor impurities or kinases copurifying with Hsp90.

Adenosine Diphosphate↗
PubMed1996

Chemical and functional studies on the importance of purple membrane lipids in bacteriorhodopsin photocycle behavior.

In native purple membrane (PM), there are approximately 1 squalene, 2 glycolipid sulfate (GLS), and 6 phospholipid (PL) molecules per bacteriorhodopsin (BR) monomer. Brief (approximately 2 min) exposure to 0.1% Triton X-100 removes about 25%, 20%, and 6% of squalenes, GLS, and PL, respectively (this paper) while causing profound changes in the BR photocycle, including the loss of 'photocooperativity'. The BR photocycle in Triton-treated PM can be restored to near normal behavior by reconstitution with native PM lipids. Isolated squalenes are not effective whereas PL alone partially restores normal photocycle characteristics.

Bacteriorhodopsins↗
PubMed1996

In vitro and in vivo inactivation of transcobalamin II receptor by its antiserum.

Rabbits injected with pure human placental transcobalamin II-receptor (TC II-R) failed to thrive with no apparent tissue or organ damage, but a 2-fold elevation of the metabolites, homocysteine, methylmalonic acid, and the ligand, transcobalamin II, in their plasma. Exogenously added transcobalamin II-[57Co]cyanocobalamin bound very poorly (2-5%) to the affected rabbit liver, kidney, and intestinal total or intestinal basolateral membrane extracts relative to the binding by membrane extracts from normal rabbit tissues. The activity was restored to normal values following a wash of affected rabbit tissue membranes with pH 3 buffer containing 200 mM potassium thiocyanate. Immunoblot analysis of normal and affected rabbit kidney and liver total membranes revealed similar amounts of 124-kDa TC II-R dimer protein. The neutralized and dialyzed extract from the affected rabbit membranes inhibited the binding of the ligand to pure TC II-R and the harvested affected rabbit serum inhibited the uptake of TC II-[57Co]cobalamin (Cbl) from the basolateral side of human intestinal epithelial (Caco-2) cells and decreased the utilization of [57Co]Cbl as coenzymes by the Cbl-dependent enzymes. The loss of exogenously added ligand binding or the binding of 125I-protein A occurred with the intestinal basolateral, but not the apical membranes. Based on these results, we suggest that circulatory antibodies to TC II-R cause its in vivo functional inactivation, suppress Cbl uptake by multiple tissues, and thus cause severe Cbl deficiency and the noted failure to thrive.

Animals↗
PubMed1996

Morphological and biological characteristics of mammogram-detected invasive breast cancer.

Thirty-nine mammographically detected, (M-detected) small invasive carcinomas of the breast (< or = 5 mm) were compared with 78 consecutive clinical cancers (> or = 10 mm) for a variety of morphological and biological markers of prognostic importance. There were more tubular carcinomas in the M-detected group (12.8% v 3.8%), but this did not reach statistical significance. Incidences of other histological types were similar. The types of associated in situ component were similar in the two groups. M-detected cancers were of lower overall grade (P < .001), lower architectural and nuclear grades (P = .0164 and P < .0001 respectively), and had fewer mitotic cells (P < .0001). None showed positive lymph nodes (P < .0001). Estrogen and progesterone receptor expression was similar in both groups. M-detected cancers expressed p53 nuclear protein less frequently than clinical cancers (P = .0398), had lower levels of microvessel density (P = .0001), and were more often diploid (P = .0131). S-phase of diploid tumors in the two groups was similar, but S-phase of aneuploid tumors was lower in the M-detected group (P = .0057). Ki67 expression was lower in M-detected cancers (P < .0001). In conclusion, M-detected small breast cancers, although invasive, represent an evolutionary phase of breast cancer that generally lacks morphological and biologic markers of aggressive behavior. The presence or absence of these markers, collectively, may explain the influence of tumor size on survival in patients with breast cancer.

Breast Neoplasms↗
PubMed1996

Ultrasound-guided thermocouple placement for cryosurgery.

BACKGROUND: Although cryosurgical methods have high cure rates, imprecise estimates of both skin lesion depth and destructive temperature front location result in subjective technique in skin malignancy treatments. OBJECTIVE: We evaluated the possibility of newer ultrasound equipment to assist in the precise placement of thermocouples in human skin. METHODS: DermaScan C ver. 3 ultrasonographic equipment fitted with a sharp focus probe with a frequency of 20 MHz and a scan length of 12.1 mm was used to locate thermocouples with 27- and 30-gauge needles. RESULTS: We successfully and reproducibly located thermocouples and thin needles, and accurately measured their distance from the skin surface. CONCLUSION: Ultrasound is a useful method for the accurate placement of thermocouples, and needles as thin as 30 gauge for monitoring in cryosurgery.

Cryosurgery↗
PubMed1996

Immunophenotype of intraductal carcinoma.

OBJECTIVE: Mammography and breast-conserving therapy have focused attention on the classification of intraductal carcinoma (IDC) and emphasized the prognostic importance of comedo versus noncomedo variants. We used histochemical markers to define the immunophenotype of 43 IDCs with respect to comedo versus noncomedo status and patterns of angiogenesis. RESULTS: Reactions in comedo carcinomas were significantly negative for estrogen receptor and progesterone receptor, and positive for p53 and HER-2/neu more often than the noncomedo variant. All seven IDCs associated with Paget's disease showed positive reactions for HER-2/neu. Basement membrane immunoreactivity for type IV collagen and laminin was discontinuous in most examples of IDC regardless of type, with a trend toward more intense staining in comedo than in noncomedo carcinomas. Periductal angiogenesis was not significantly related to the type of IDC but was more pronounced with comedo carcinomas. CONCLUSIONS: These observations indicate that there are immunophenotypic correlates to the current structural classification of IDC. The immunophenotype of IDC is helpful in subclassifying an IDC and could prove useful as a prognostic indicator for local control in patients treated by breast-conserving therapy.

Adult↗