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Biomedical subjects

S Shetty

Publications and source records attributed to S Shetty.

13 recordsLinked to original sources

Urokinase receptor in human malignant mesothelioma cells: role in tumor cell mitogenesis and proteolysis.

Urokinase (uPA) interacts with its receptor (uPAR) to promote proteolysis and tumor migration, functions of potential importance in the pathogenesis of malignant mesothelioma. Immunohistochemistry of human malignant mesothelioma tissue and mesothelioma cells (MS-1) showed that mesothelioma cells express uPAR. We isolated uPAR from MS-1 cells by metabolic labeling and showed that it could be induced by phorbol myristate acetate (PMA), lipopolysaccharide (LPS), a transforming growth factor-beta (TGF-beta) or tumor necrosis factor-alpha (TNF-alpha). Experiments with MS-1 cells showed that uPA binding was saturable, specific, and reversible with a mean dissociation constant (Kd) of 5.4 +/- 1.1 nM. Binding was inhibited by a blocking antibody to uPAR and by the uPA amino-terminal fragment (ATF), but not by low molecular weight uPA. uPAR expression was regulated transcriptionally and translationally; antisense oligonucleotides blocked expression of uPAR protein. Plasminogen activator inhibitor-1 (PAI-1) inhibited PA activity of preformed uPA/uPAR complexes and increased cycling of the receptor from the cell surface. Stimulation of subconfluent MS-1 cells by high molecular weight or recombinant uPA, but not ATF or low molecular weight fragment, caused concentration-dependent incorporation of [3H]thymidine. These data indicate a novel mechanism by which malignant mesothelioma cells localize pericellular proteolysis and concurrently regulate tumor cell proliferation.

Cell Cycle

Purification of a growth factor from pigeon milk.

Aqueous extracts of pigeon milk (PM) stimulated the in vitro growth of quiescent CHO cells maintained in culture and caused precocial incisor eruption and eyelid opening in newborn mice. CM-cellulose chromatography of the growth factor of PM enhanced its biologic activity. Rechromatography of CM-active fractions in DEAE-cellulose columns yielded a single peak that was mitogenic both in vivo and in vitro. SDS-PAGE of DEAE-active fractions gave rise to a single band of molecular weight about 6000. This protein, termed as pigeon milk-derived growth factor (PMGF), yielded a single peak on gel filtration in Sephadex G-100 columns. Elution pattern of PMGF was similar to that obtained for epidermal growth factor of mouse submaxillary gland (mEGF). The chromatographic plus electrophoretic pattern, and biologic action of PMGF suggest it to be a EGF-like protein.

Animals

Phenotype, activation and lymphokine secretion by gamma/delta T lymphocytes from schistosomiasis and carcinoma of the urinary bladder.

In humans the majority of the CD3+ T cells usually express an alpha/beta T cell receptor (TcR) and a minority express a gamma/delta TcR. The CD3+ TcR alpha/beta and CD3+ TcR gamma/delta cells from blood of the patients with schistosomiasis with carcinoma of the urinary bladder (SCB) were analyzed for phenotype, activation, secretion of interleukin 2 (IL 2). B cell growth factor (BCGF) and B cell differentiation factor (BCDF), as well as for autologous (AMLR) and allogeneic (MLR) mixed lymphocyte reaction. Patients with SCB had a highly increased percentage of CD3+ TcR gamma/delta and a decreased percentage of CD3+ TcR alpha/beta T cells in their circulation. These CD3+ TcR gamma/delta T cells expressed the CD25 (IL 2 receptor), CD38, CD71 (transferrin receptor) and HLA-DR activation antigens at a higher intensity after in vitro stimulation with recombinant IL 2, phytohemagglutinin and soluble egg antigen (from Schistosoma haematobium). The SCB patients' CD3+ TcR gamma/delta T cells were highly deficient in secretion of IL 2 but produced highly elevated levels of BCGF and BCDF. On the contrary, both BCGF and BCDF activities of the CD3+ TcR alpha/beta T cells were decreased. Moreover, CD3+ TcR gamma/delta T cells demonstrated highly deficient AMLR and MLR activity. These observations suggest a possible role of CD3+ TcR gamma/delta T cells in the immune response and the disease pathogenesis in human schistosomiasis infections.

Animals

Soluble interleukin-2 receptor levels and immune activation in patients with schistosomiasis and carcinoma of the urinary bladder.

Soluble interleukin-2 receptor (sIL-2R) level in serum is a marker of immune regulation and lymphocyte activation. Highly elevated levels of sIL-2R in serum were observed in patients of schistosomiasis with carcinoma of the bladder (SCB) and carcinoma of the bladder without schistosomiasis (CB) compared with patients with carcinoma of the prostate with or without schistosomiasis and normal healthy controls. Patients with SCB, who had an elevated percentage of cells expressing CD38+ activation antigen and CD71+ transferrin receptors in circulation, also had elevated levels of sIL-2R in serum. There were few interleukin-2 receptor (CD25+) positive cells in circulation in some patients with SCB. Despite this, the sIL-2R levels were extremely elevated. Our data suggest that in SCB, CD38+ and CD71+ cells may be the source of secretion of sIL-2R in serum. This relationship was confirmed by phenotypic characterizations of mononuclear cells and sIL-2R levels in individual patients. Measurements of sIL-2R levels in serum may provide a sensitive method of immune activation in patients with SCB.

Antigens, CD

Stimulatory effect of pigeon milk growth factor on protein and nucleic acid synthesis in neonate mice.

Effect of subcutaneously administered pigeon milk-derived growth factor (PMGF) on protein and nucleic acid content of various body organs was studied in neonate mice. Although the body and organ weights of PMGF-treated mice did not differ from those of controls, the weight of testes was significantly higher in the former than the latter. The treated animals had significantly greater content of protein (in liver and skin), DNA (in liver, lung, stomach, duodenum, ileum and rectum) and RNA (in liver, stomach, ileum and skin). The protein/DNA ratio was lower in many organs of PMGF-treated mice. These results indicate that the biological properties of PMGF bear semblance to those of epidermal growth factor isolated from mouse salivary gland and human milk.

Animals

Impact of schistosomiasis on urinary bladder cancer in the southern province of Saudi Arabia: review of 60 cases.

The histopathologic findings reported in 254 consecutive urinary bladder biopsies were reviewed. Evidence of urinary schistosomiasis was identified in 88 biopsies (35%) and malignant neoplasms were diagnosed in 60 cases (24%). Nine out of 60 (15%) cases of bladder cancer had urinary bladder schistosomiasis and the remaining 51 cases (85%) had no clinical evidence of schistosomiasis. Transitional cell carcinoma was the commonest type of urinary bladder cancer (70%) followed by squamous cell carcinoma (20%) adenocarcinoma (8%) and rhabdomyosarcoma (2%). The mean age of the patients included was 60 +/- 15 years and the male:female ratio was 9:1. Comparison of our findings to those reported from other provinces of Saudi Arabia and from other countries, including those with known high incidence of schistosomiasis, is included.

Adenocarcinoma

T-cell abnormality and defective interleukin-2 production in patients with carcinoma of the urinary bladder with schistosomiasis.

Patients with schistosomiasis of the urinary bladder (SB) and schistosomiasis with carcinoma of the urinary bladder (SCB) had significantly increased percentage of IL-2R-, HLA-DR-, and transferrin receptor (T9)-bearing T cells in circulation. The percentage of these activated T cells decreased by in vitro culture with PHA but increased by Schistosoma haematobium soluble egg antigen. These patients with SB and SCB had a PHA-specific defect in IL-2 production. A functional defect with induction of IL-2R-positive suppressor monocytes appears to correlate with the defective PHA-induced IL-2 production by CD4+ T cells and monocytes. Disordered regulation of PHA-induced IL-2 production by the CD4+ T cells and monocytes may be the key feature in the highly depressed cell-mediated immune response in schistosomiasis. However, immune activation and significantly elevated IL-2 production in response to disease-specific S. haematobium soluble egg antigen may be related with the pathogenesis of SB and SCB. Thus, S. haematobium-specific CD4+ T cells are present in schistosomiasis, and their function is determined by adequate release of IL-2-and/or IL-2R-bearing CD11+ suppressor monocytes.

Adult

Activated CD4-positive T-lymphocytes and impaired cell-mediated immunity in patients with carcinoma of the urinary bladder with schistosomiasis.

Patients with schistosomiasis of the urinary bladder (SB) associated with carcinoma of the bladder (SCB) or carcinoma of the prostate (SCP) have a variety of immunologic abnormalities, including the presence of HLA-DR+ and interleukin-2 receptor-positive (IL-2R+) T-lymphocytes in circulating blood. This study demonstrated that, the HLA-DR+ and IL-2R+ antigens are selectively expressed on majority of the CD4+ T-lymphocytes of patients with SCB, whereas, these antigens are expressed almost equally on both CD4+ and CD8+ T-lymphocytes of patients with SB and SCP. Expressions of HLA-DR+ and IL-2R+ antigens in CD4+ T-lymphocytes, and a depressed response of this T-cell subset to phytohemagglutinin and Concanavalin A stimulations seems to be the characteristic feature of these patients with SCB. In addition, the autologous mixed lymphocyte reaction (AMLR) and allogenic mixed lymphocyte reaction (MLR) was depressed in patients with SCB. However, patients with SCP demonstrated a normal MLR, even though the AMLR was highly depressed. The immunoregulatory role of the HLA-DR+, IL-2R+, CD4+ helper/inducer T-lymphocytes, and the AMLR and MLR abnormalities we have identified in patients with SCB may be important and could play a role in the pathobiology of these diseases in humans.

Adenocarcinoma

Observations on bacteria associated with pigeon crop.

Lactobacilli, streptococci and coliforms of pigeon crop contents, 5th wash, macerate and those of first-day pigeon milk have been studied. Streptococci predominated in all the samples tested. Relatively higher counts of lactobacilli and streptococci in crop macerate than in the 5th wash suggested the adhesion of these bacteria to crop wall. Because of frequent occurrence in crop of partially digested fibrous food, its contents were tested for the presence of cellulolytic bacteria. The results indicated that four isolates were capable of utilizing cellulose with the resultant production of reducing sugars. It is inferred that the crop microflora is involved in the degradation of dietary fibre in the pigeon.

Animals

Surgical treatment of T and Y fractures of the distal humerus.

Intercondylar T and Y fractures of the distal humerus in adults present a challenge. Open reduction and internal fixation in 19 cases over a 7-year period gave excellent or good results in 15 cases. Campbell's posterior approach to the elbow joint gave a satisfactory exposure. Anterior transposition of the ulnar nerve is a very useful adjunct to prevent late neuritis. A new method of classification is suggested, taking into account the importance of the supracondylar ridge for adequate stability.

Bone Screws

Carbohydrates of pigeon milk and their changes in the first week of secretion.

The carbohydrate content of pigeon crop secretion called pigeon milk (PM) was in the range of 0.9-1.5%. Sugars of trichloroacetic acid soluble (TCA-S) fraction increased by 67% between day-1 and day-5 of secretion while those of TCA- insoluble (TCA-P) fraction remained fairly constant. Sialic acids constituted 5-9% of carbohydrates. The proportion of lipid- and protein-bound sialic acids was 51% and 31% respectively; the former increased from 41% to 68% between day-1 and day-5 whereas the latter decreased from 45% to 21% during the corresponding period. Some of the sugars of PM were fucose (40%), glucosamine (31%), galactose (12%), mannose (9%) and glucose (8%). The free sugars whose content was very low (0.05%) included fucose, mannose, glucose and some unidentified oligosaccharides. The proportion of lipid- and protein-bound sugars was 31% and 63% respectively; the former decreased by 7% from day-1 to day-5 while the latter increased by 11% during the same period. Gel chromatography of PM confirmed the presence of sialic acids and glucosamine; the latter existed both in free and bound form. The nature of changes in the carbohydrate composition of PM in the first week of secretion was more quantitative than qualitative.

Animals