Search PubMed⌕ Search

Biomedical subjects

D D Patel

Publications and source records attributed to D D Patel.

At least 55 records · Page 3Linked to original sources
PubMed2000

Prolactin as a local growth promoter in patients with breast cancer: GCRI experience.

AIMS: The aim of this study was to evaluate the prognostic value of pre-operative prolactin (PRL) in conjunction with established prognosticators, and the risk of disease relapse in patients with early and advanced breast cancer. To confirm the hypothesis that PRL is produced by breast tumours molecular analysis of PRL, using immunohistochemistry, mRNA by RT-PCR and direct sequencing, was performed. Furthermore, presence of prolactin receptors (PRLR) was evaluated by immunohistochemical localization in these patients. METHODS: In 111 breast cancer patients, pre-operative PRL was determined by an immunoradiometric assay (IRMA) method. Immunohistochemical localization of PRL (IHL-PRL) and PRLR was performed on formalin-fixed, paraffin-embedded tissue sections. Expression of PRL mRNA was carried out by reverse transcriptase polymerase chain reaction (RT-PCR). RT-PCR PRL amplimer was sequenced and compared with human pituitary PRL amplimer. RESULTS: Fifty-eight per cent (64/111) of the patients had hyperprolactinaemia (PRL520.0 ng/ml). With increasing tumour size, a higher incidence of hyperprolactinaemia was noted which was statistically significant (r=0.34, P=0.0001). In stage III patients, and in node positive patients, the incidence of hyperprolactinaemia was significantly higher compared to their respective counterparts (stage II vs stage III, r=0.37, P=0.00006; node negative vs node positive, r=0.30, P=0.001). Hyperprolactinaemic patients had a significantly higher risk of developing recurrent/metastatic disease and a higher mortality risk as compared to patients with PRL <20.0 ng/ml. The multivariate survival analysis indicated that apart from disease stage, prognosis of patients with pre-operative hyperprolactinaemia was poorer than that of patients with PRL <20.0 ng/ml. Seventy-eight per cent (87/111) of the tumours showed positive immunoreactivity with PRL antibody indicating that PRL, or a similar molecule, is produced ectopically by breast tumours. PRL mRNA expression using RT-PCR confirmed the de novo synthesis of PRL. PRL mRNA expression was seen in 52% (33/63) of tumours. Sequence analysis of the 234 bp PRL amplimer revealed that the sequence was homologous to the sequence of exon 5 of human pituitary PRL mRNA. Furthermore, PRLR were present in 80% of tumours detected by immunohistochemical localization. A significant positive correlation was noted between IHL-PRL and PRLR (r=0.26, P=0.006). CONCLUSIONS: This multifaceted study of PRL suggests that breast cancer cells produce PRL and that this ectopically produced PRL may act as a major local growth promoter via autocrine and paracrine mechanisms. It may provide new insights into endocrine treatment of breast cancer.

Adult↗
PubMed2000

The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection.

The human thymus is a complex chimeric organ comprised of central (thymic epithelial space) and peripheral (perivascular space) components that functions well into adult life to produce naive T lymphocytes. Recent advances in identifying thymic emigrants and development of safe methods to study thymic function in vivo in adults have provided new opportunities to understand the role that the human thymus plays in immune reconstitution in aging, in bone marrow transplantation, and in HIV-1 infection. The emerging concept is that there are age-dependent contributions of thymic emigrants and proliferation of postthymic T cells to maintain the peripheral T cell pool and to contribute to T cell regeneration, with the thymus contributing more at younger ages and peripheral T cell expansion contributing more in older subjects. New studies have revealed a dynamic interplay between postnatal thymus output and peripheral T cell pool proliferation, which play important roles in determining the nature of immune reconstitution in congenital immunodeficiency diseases, in bone marrow transplantation, and in HIV-1 infection. In this paper, we review recent data on human postnatal thymus function that, taken together, support the notion that the human thymus is functional well into the sixth decade and plays a role throughout life to optimize human immune system function.

Aging↗
PubMed2000

Bleomycin-induced chromosome damage in lymphocytes indicates inefficient DNA repair capacity in breast cancer families.

In vitro mutagen susceptibility has been observed as a predictor of cancer risk. To evaluate susceptibility to mutagen, we have studied the response to in vitro bleomycin (BLM) treatment in cultured peripheral blood lymphocytes (PBL) of 9 breast cancer families (BCFs). Eleven breast cancer patients (BCPs) and 36 healthy blood relatives (HBRs) from BCFs were included in the study. Data were compared with 22 healthy control women. The frequencies of chromosomal aberrations were evaluated after exposure to BLM in the last five hours. Mean frequency of BLM-induced chromosomal aberrations per cell (CA) observed among BCPs was significantly higher as compared to their HBRs as well as control subjects. Moreover, mean BLM-induced CA/cell value observed for HBRs was also significantly higher than that of control subjects. In comparison to controls, it was observed that there was four times more cancer risk in BCPs (OR=4.148, 95% CI=5.83-687.46) and 2.5 times more cancer risk in HBRs (OR=2.67, 95% CI=5.31-39.25). Lymphocytes from 90% of BCPs and 69% of HBRs were found to be sensitive to BLM (using a cutoff value = controls group mean + 1 SD). Thus, lymphocytes of BCPs and their HBRs were more sensitive to BLM exposure as compared to controls. Our finding indicated inefficient DNA repair capacity in BCFs. The HBRs in BCFs, having increased BLM-sensitivity, may be at higher risk to develop a similar cancer.

Adult↗
PubMed1999

Assessment of glutathione-S-transferase and glutathione reductase in patients with squamous-cell carcinoma of buccal mucosa.

Serum and tumor cytosolic levels of glutathione-S-transferase (GST) and glutathione-reductase (GR) activity were determined spectrophotometrically. The levels were correlated with clinicopathological criteria and a tobacco-associated protein band (T band) found in serum. The results showed significantly decreased mean serum GST levels (p < 0.02) in cancer patients as compared with controls. However, mean serum GR levels were significantly higher in patients than in controls (p < 0.01). T-band-positive patients showed low GST and low GR activity as compared with T-band-negative patients. Tumor cytosolic-enzyme levels of GST and GR activity were significantly higher (p < 0.0003 and p < 0.0001, respectively) than in corresponding adjacent noncancerous mucosa. Tumour cytosolic GST and GR activity showed significant association with clinicopathologic criteria, e.g., stage, histologic grade and nodal involvement. T-band-negative patients showed significantly higher levels of GST (p < 0.0001) than did T-band-positive patients. Low levels of cytosolic GST may be associated with increased susceptibility towards carcinogen-induced damage. The results suggest that the presence of T band in the sera may be associated with a high-risk phenotype due to decreased detoxification ability.

Adult↗
PubMed1999

Resistance of CD7-deficient mice to lipopolysaccharide-induced shock syndromes.

CD7 is an immunoglobulin superfamily molecule involved in T and natural killer (NK) cell activation and cytokine production. CD7-deficient animals develop normally but have antigen-specific defects in interferon (IFN)-gamma production and CD8(+) CTL generation. To determine the in vivo role of CD7 in systems dependent on IFN-gamma, the response of CD7-deficient mice to lipopolysaccharide (LPS)-induced shock syndromes was studied. In the high-dose LPS-induced shock model, 67% of CD7-deficient mice survived LPS injection, whereas 19% of control C57BL/6 mice survived LPS challenge (P < 0.001). CD7-deficient or C57BL/6 control mice were next injected with low-dose LPS (1 microgram plus 8 mg D-galactosamine [D-gal] per mouse) and monitored for survival. All CD7-deficient mice were alive 72 h after injection of LPS compared with 20% of C57BL/6 control mice (P < 0.001). After injection of LPS and D-gal, CD7-deficient mice had decreased serum IFN-gamma and tumor necrosis factor (TNF)-alpha levels compared with control C57BL/6 mice (P < 0.001). Steady-state mRNA levels for IFN-gamma and TNF-alpha in liver tissue were also significantly decreased in CD7-deficient mice compared with controls (P < 0.05). In contrast, CD7-deficient animals had normal liver interleukin (IL)-12, IL-18, and interleukin 1 converting enzyme (ICE) mRNA levels, and CD7-deficient splenocytes had normal IFN-gamma responses when stimulated with IL-12 and IL-18 in vitro. NK1.1(+)/ CD3(+) T cells are known to be key effector cells in the pathogenesis of toxic shock. Phenotypic analysis of liver mononuclear cells revealed that CD7-deficient mice had fewer numbers of liver NK1.1(+)/CD3(+) T cells (1.5 +/- 0.3 x 10(5)) versus C57BL/6 control mice (3.7 +/- 0.8 x 10(5); P < 0.05), whereas numbers of liver NK1.1(+)/CD3(-) NK cells were not different from controls. Thus, targeted disruption of CD7 leads to a selective deficiency of liver NK1.1(+)/ CD3(+) T cells, and is associated with resistance to LPS shock. These data suggest that CD7 is a key molecule in the inflammatory response leading to LPS-induced shock.

Animals↗
PubMed1999

A 43-nucleotide RNA cis-acting element governs the site-specific formation of the 3' end of a poxvirus late mRNA.

The 3' ends of late mRNAs of the ati gene, encoding the major component of the A-type inclusions, are generated by endoribonucleolytic cleavage at a specific site in the primary transcript [Antczak et al., (1992), Proc. Natl. Acad. Sci. USA 89, 12033-12037]. In this study, sequence analysis of cDNAs of the 3' ends of ati mRNAs showed these mRNAs are 3' polyadenylated at the RNA cleavage site. This suggests that ati mRNA 3' end formation involves cleavage of a late transcript, with subsequent 3' polyadenylation of the 5' cleavage product. The RNA cis-acting element, the AX element, directing orientation-dependent formation of these mRNA 3' ends, was mapped to a 345-bp AluI-XbaI fragment. Deletion analyses of this fragment showed that the boundaries of the AX element are within -5 and +38 of the RNA cleavage site. Scanning mutagenesis showed that the AX element contains at least two subelements: subelement I, 5'-UUUAU downward arrowCCGAUAAUUC-3', containing the cleavage site ( downward arrow), separated from the downstream subelement II, 5'-AAUUUCGGAUUUGAAUGC-3', by a 10-nucleotide region, whose composition may be altered without effect on RNA 3' end formation. These features, which differ from those of other elements controlling RNA processing, suggest that the AX element is a component of a novel mechanism of RNA 3' end formation.

Animals↗
PubMed1999

Evaluation of glycoprotein constituents in head and neck cancer patients undergoing radiotherapy.

BACKGROUND: Alterations in serum levels of several glycoprotein constituents are reported to be useful for treatment monitoring of cancer patients. The purpose of this study was to determine efficacy of sialic acid and seromucoid fraction as treatment monitors for head and neck (H&N) cancer patients undergoing radiotherapy (RT). METHODS: Serum levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), and seromucoid fraction (measured as Mucoid protein [MP] and hexose) were studied in age matched controls and in patients with H&N cancer at diagnosis and during/after completion of RT. The markers were estimated by spectrophotometric methods. RESULTS: Serum levels of sialic acid forms and seromucoid fraction were significantly elevated (p<.001) in untreated H&N cancer patients (n = 32) as compared with controls (n = 50). The marker levels were significantly declined (p<.001) in H&N cancer patients who responded to RT as compared with their levels at diagnosis, whereas the levels were persistently elevated in nonresponders. CONCLUSION: Evaluation of sialic acid forms and seromucoid fraction could be used for monitoring the treatment of H&N cancer patients undergoing RT.

Adult↗
PubMed1999

Chromosomal aberrations in young cancer patients.

Spontaneous level of chromosomal aberrations (CA) is considered to be indicative of inherent cancer predisposition, which plays a major role in total cancer incidence. We have studied spontaneous CA levels in in vitro cultured peripheral blood lymphocytes of pediatric cancer patients (n = 77). Results were compared with those of control subjects (n = 72), including: age-matched controls; elder controls (minimum age 60 years); and healthy first-degree relatives (FDR) of pediatric cancer patients. Pediatric cancer patients showed the highest mean CA/cell value, which was statistically significant as compared to their age-matched counterparts, elder controls, and the FDRs. As compared to 7% of all the three control groups collectively, 32.4% of pediatric cancer patients showed > 0.1 mean CA/cell value. One of the FDRs with a very high frequency of CA developed cancer within three years. The results suggest that spontaneous levels of chromosomal aberrations may be used as one of the biomarkers for cancer predisposition study.

Adolescent↗
PubMed1999

Evaluation of telomerase activation in head and neck cancer.

During replication of the linear chromosomes, telomeres, i.e. the ends of the chromosomes, are not replicated completely by the conventional DNA polymerases. Therefore, normal somatic cells senesce after certain number of cell divisions. Telomerase is a special reverse transcriptase used by most eukaryotes to achieve immortalization. Telomerase activity has been determined in a variety of cancers. However, there are few reports on telomerase activity in head and neck cancer. The etiology of the disease in India is completely different from Western countries. Tobacco consumption is more prevalent in India and the mode of tobacco consumption (e.g. chewing, snuffing, bidi smoking, reverse smoking) is also different. The present study determined telomerase activity in 32 malignant tumour samples of head and neck cancer patients, 11 samples from patients with precancerous/benign lesions and 30 samples of adjacent normal tissues. Telomerase was found to be activated in 80% of the patients with head and neck cancer, 100% of the patients with precancerous/benign lesions and 74% of the adjacent normal tissues. According to the theory of field cancerization, carcinogenic insults (e.g. tobacco) may result into multiple malignant foci. This fact may explain the reason for high telomerase positivity in adjacent normal as well as precancerous/benign tissues. Telomerase activation and the clinical or histopathological characteristics of the head and neck cancer patients were observed to be independent features. This is a preliminary report which has generated a greater interest for in-depth elucidation of the role of telomerase and telomeres in head and neck carcinogenesis in India.

Adult↗
PubMed1999

Congenital infantile fibrosarcoma.

Infantile fibrosarcoma is a rare tumour in the paediatric age group. It occurs mainly in children below the age of 5 years. About 200 cases have been reported in the literature so far, very few of them in new-borns. We present here a case of infantile fibrosarcoma in a 27-day-old baby.

Arm↗
PubMed1999

Malignant lymphoma of the gastrointestinal tract.

AIMS: The gastrointestinal tract (GIT) is the most common site of extra-nodal lymphoma. Most of these lymphomas arise from mucosa associated lymphoid tissue (MALT). We attempt in this study to define the natural history and treatment outcome of this type of lymphoma. METHODS: We carried out a retrospective study of patients presenting at our centre with histopathological diagnosis of primary GIT lymphoma between 1990 and 1994. RESULTS: Equal numbers of cases of stomach and small bowel lymphoma were found. Vomiting and feeling of fullness were the two most common presenting symptoms. Large cell type and high grade tumours were found to be the commonest histological types. All the patients were treated with surgery followed by chemotherapy. A 5-year disease-free survival (DFS) rate of 73%) was observed with a confidence interval of 0.65-1.35. Survival in stomach cancer was 73.5% (95% CI 0.26-1.74) while it was 76.4% in small bowel tumours (95% CI 0.54-1.46). The difference in survival was not statistically significant. CONCLUSIONS: Although there is no consensus regarding treatment of primary GI lymphoma, surgery and adjuvant chemotherapy yield good survival.

Diagnosis, Differential↗
PubMed1999

Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection.

A key question in understanding the status of the immune system in HIV-1 infection is whether the adult thymus contributes to reconstitution of peripheral T lymphocytes. We analyzed the thymus in adult patients who died of HIV-1 infection. In addition, we studied the clinical course of HIV-1 infection in three patients thymectomized for myasthenia gravis and determined the effect of antiretroviral therapy on CD4(+) T cells. We found that five of seven patients had thymus tissue at autopsy and that all thymuses identified had inflammatory infiltrates surrounding lymphodepleted thymic epithelium. Two of seven patients also had areas of thymopoiesis; one of these patients had peripheral blood CD4(+) T-cell levels of <50/mm3 for 51 months prior to death. Of three thymectomized patients, one rapidly progressed to AIDS, one progressed to AIDS over seven years (normal progressor), whereas the third remains asymptomatic at least seven years after seroconversion. Both latter patients had rises in peripheral blood CD4(+) T cells after antiretroviral therapy. Most patients who died of complications of HIV-1 infection did not have functional thymus tissue, and when present, thymopoiesis did not prevent prolonged lymphopenia. Thymectomy before HIV-1 infection did not preclude either peripheral CD4(+) T-cell rises or clinical responses after antiretroviral therapy.

Adolescent↗
PubMed1998

Mitomycin C induced chromosomal aberrations in young cancer patients.

Mitomycin-C (MMC) induced Chromosomal aberration (CA) frequencies were studied in 48 h peripheral blood lymphocyte (PBL) cultures of untreated cancer patients of young age (maximum age 12 years, n=77). Control population (n=71) consisted of age-matched group (maximum age 12 years, n=21); elder controls (minimum age 60 years, n=19) and healthy first degree relatives, i.e., parents or siblings of the pediatric cancer patients (mean age 24.3 years, n=31) as they share their genome and environment. Induced CA levels were found to be significantly higher among pediatric cancer patients as compared to control groups. The age-matched and elder control groups showed comparable CA levels. The first degree relatives controls showed higher induced CA levels as compared to pediatric and elder control groups. The present results indicate that there are different degrees of mutagen sensitivity prevailing in normal population. This may be responsible for differential cancer proneness. High degree of mutagen sensitivity in cancer patients may also be playing a major role in cancer onset at an early age.

Adult↗
PubMed1998

Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow.

Leukocyte migration into sites of inflammation involves multiple molecular interactions between leukocytes and vascular endothelial cells, mediating sequential leukocyte capture, rolling, and firm adhesion. In this study, we tested the role of molecular interactions between fractalkine (FKN), a transmembrane mucin-chemokine hybrid molecule expressed on activated endothelium, and its receptor (CX3CR1) in leukocyte capture, firm adhesion, and activation under physiologic flow conditions. Immobilized FKN fusion proteins captured resting peripheral blood mononuclear cells at physiologic wall shear stresses and induced firm adhesion of resting monocytes, resting and interleukin (IL)-2-activated CD8(+) T lymphocytes and IL-2-activated NK cells. FKN also induced cell shape change in firmly adherent monocytes and IL-2-activated lymphocytes. CX3CR1-transfected K562 cells, but not control K562 cells, firmly adhered to FKN-expressing ECV-304 cells (ECV-FKN) and tumor necrosis factor alpha-activated human umbilical vein endothelial cells. This firm adhesion was not inhibited by pertussis toxin, EDTA/EGTA, or antiintegrin antibodies, indicating that the firm adhesion was integrin independent. In summary, FKN mediated the rapid capture, integrin-independent firm adhesion, and activation of circulating leukocytes under flow. Thus, FKN and CX3CR1 mediate a novel pathway for leukocyte trafficking.

Cell Adhesion↗
PubMed1998

Oxidized alpha2-macroglobulin (alpha2M) differentially regulates receptor binding by cytokines/growth factors: implications for tissue injury and repair mechanisms in inflammation.

Alpha2M binds specifically to TNF-alpha, IL-1beta, IL-2, IL-6, IL-8, basic fibroblast growth factor (bFGF), beta-nerve growth factor (beta-NGF), platelet-derived growth factor (PDGF), and TGF-beta. Since many of these cytokines are released along with neutrophil-derived oxidants during acute inflammation, we hypothesize that oxidation alters the ability of alpha2M to bind to these cytokines, resulting in differentially regulated cytokine functions. Using hypochlorite, a neutrophil-derived oxidant, we show that oxidized alpha2M exhibits increased binding to TNF-alpha, IL-2, and IL-6 and decreased binding to beta-NGF, PDGF-BB, TGF-beta1, and TGF-beta2. Hypochlorite oxidation of methylamine-treated alpha2M (alpha2M*), an analogue of the proteinase/alpha2M complex, also results in decreased binding to bFGF, beta-NGF, PDGF-BB, TGF-beta1, and TGF-beta2. Concomitantly, we observed decreased ability to inhibit TGF-beta binding and regulation of cells by oxidized alpha2M and alpha2M*. We then isolated alpha2M from human rheumatoid arthritis synovial fluid and showed that the protein is extensively oxidized and has significantly decreased ability to bind to TGF-beta compared with alpha2M derived from plasma and osteoarthritis synovial fluid. We, therefore, propose that oxidation serves as a switch mechanism that down-regulates the progression of acute inflammation by sequestering TNF-alpha, IL-2, and IL-6, while up-regulating the development of tissue repair processes by releasing bFGF, beta-NGF, PDGF, and TGF-beta from binding to alpha2M.

Animals↗