Search PubMed⌕ Search

Biomedical subjects

D D Patel

Publications and source records attributed to D D Patel.

At least 109 records · Page 6Linked to original sources
PubMed1995

Identification and characterization of a 100-kD ligand for CD6 on human thymic epithelial cells.

CD6 is a 130-kD glycoprotein expressed on the surface of thymocytes and peripheral blood T cells that is involved in TCR-mediated T cell activation. In thymus, CD6 mediates interactions between thymocytes and thymic epithelial (TE) cells. In indirect immunofluorescence assays, a recombinant CD6-immunoglobulin fusion protein (CD6-Rg) bound to cultured human TE cells and to thymic fibroblasts. CD6-Rg binding to TF and TE cells was trypsin sensitive, and 54 +/- 4% of binding was divalent cation dependent. By screening the blind panel of 479 monoclonal antibodies (mAbs) from the 5th International Workshop on Human Leukocyte Differentiation Antigens for expression on human TE cells and for the ability to block CD6-Rg binding to TE cells, we found one mAb (J4-81) that significantly inhibited the binding of CD6-Rg to TE cells (60 +/- 7% inhibition). A second mAb to the surface antigen identified by mAb J4-81, J3-119, enhanced the binding of CD6-Rg to TE cells by 48 +/- 5%. Using covalent cross-linking and trypsin digestion, we found that mAb J4-81 and CD6-Rg both bound to the same 100-kD glycoprotein (CD6L-100) on the surface of TE cells. These data demonstrate that a 100-kD glycoprotein on TE cells detected by mAb J4-81 is a ligand for CD6.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed1995

AD2, a human molecule involved in the interaction of T cells with epidermal keratinocytes and thymic epithelial cells.

Interactions between T cells and epithelial cells of the thymus are essential for normal T cell development, and interactions between T cells and skin epidermal keratinocytes occur in the context of inflammatory skin diseases and cutaneous T cell malignancies. On the basis of observations that the T cell ALL cell line, HSB, bound to IFN-gamma activated epidermal keratinocytes (41 +/- 5% of EK with three or more HSB cells bound), whereas the CTCL cell line H9 bound poorly (8 +/- 3%), we have raised mAb 13H12 that identified a 36 kDa molecule, termed AD2, that was highly expressed on HSB but not on H9 T cells. mAb 13H12 inhibited the binding of HSB T cells to IFN-gamma-treated epidermal keratinocytes (43 +/- 5% inhibition, p < 0.01), inhibited the binding of peripheral blood T cells to IFN-gamma-treated EK (62 +/- 3% inhibition, p < 0.001), and inhibited the binding of IFN-gamma-treated human thymic epithelial cells to thymocytes (39 +/- 3% inhibition, p < 0.01). Although AD2 was expressed at a low level on all T cells, AD2 was highly expressed on the CD3-CD4-CD8-, CD3-CD4low+ CD8-, and CD3-CD4+ CD8+ subsets of immature thymocytes in the thymic subcapsular and inner cortex. Taken together, these data suggest a role for the AD2 molecule in interactions of T cells with epithelial cells of skin and thymus.

Animals↗
PubMed1995

Physical and genetic linkage of the genes encoding Ly-9 and CD48 on mouse and human chromosomes 1.

By virtue of sequence similarity, the genes encoding CD2, CD48, CD58, and Ly-9 have been assigned to a distinct subset within the immunoglobulin superfamily. Previous gene mapping studies in human and mouse have suggested that CD2, CD48, and CD58 arose by gene duplication. Here we show the gene encoding Ly-9 to be located adjacent to CD48 and the Na,K-ATPase alpha 2 subunit gene on human and mouse chromosome 1. The proximity in human and mouse genomes of the genes encoding CD2, CD58, and the Na,K-ATPase alpha 1 subunit, and of the Ly-9, CD48, and the Na,K-ATPase alpha 2 subunit genes may be explained by the occurrence of two, successive duplication events during vertebrate evolution, and suggest that Ly-9 may also participate in adhesion reactions between T lymphocytes and accessory cells by homophilic interaction.

Animals↗
PubMed1995

Characterization of human thymic epithelial cell surface antigens: phenotypic similarity of thymic epithelial cells to epidermal keratinocytes.

Cellular interactions between developing thymocytes and cells of the thymic microenvironment are necessary for maturation of thymocytes into mature T cells. While much is known about the molecules on developing T cells that mediate these interactions, little is known about the surface molecules of human thymic epithelial (TE) cells. In this study, using a panel of 276 MAb including 255 MAb from the 5th International Workshop on Human Leukocyte Differentiation Antigens (HLDA-V), we have determined the expression of CD1 through CDw130 and other surface molecules on resting and IFN-gamma-activated cultured human TE cells and on resting epidermal keratinocytes (EK). We demonstrate the surface expression of 50 of the 161 molecules assayed for on TE cells, including a number of adhesion molecules, cytokine receptors, Apo-1, and MHC-encoded molecules. While activation of TE cells with IFN-gamma for 48 hr induced a greater than fivefold increase in the expression of four surface molecules (CD38, CD54, MHC class I, and MHC class II), it also induced a greater than 50% increase in the expression of 14 other surface molecules (CD12, CD29, CD40, CD44, CD47, CD49b, CD49c, CD49e, CD55, CD66, CD87, CD104, TE4, and STE3) and a decrease in the expression of three molecules (CDw65, CDw109, and STE2). In comparing the phenotype of TE cells to 83 other cell lines studied in HLDA-V, we found that TE cells were strikingly more similar to EK than to any of the other cell types tested.

Antigens, CD↗
PubMed1995

Prognostic value of insulin-like growth factor-1 receptors in patients with colon/rectal cancer: correlation with plasma prolactin.

Prognostic value of IGF-1 receptors (IGF-1R) was evaluated and compared with circulating prolactin (PRL) in 59 patients with Dukes B or C colon/rectal cancer. IGF-1R was estimated by radioligand binding assay and PRL was estimated by immunoradiometric assay. Eighty-five percent (50/59) of patients had IGF-1R- tumours while IGF-1R positivity was observed in only 15% (9/59) of patients. None of the clinicopathological parameters showed any association with IGF-1R status. No significant difference was observed in overall survival period between patients with IGF-1R+ tumours and those with IGF-1R- tumours. However, a significant difference in overall survival time was observed between patients with PRL < 20.0 and > 20.0 ng/ml plasma (X2 = 4.70, df = 1, P < 0.05). In bivariate analysis, patients with IGF-1R- tumours and concomitant hyperprolactinemia had unfavourable prognosis compared to their counterpart (X2 = 4.21, df = 1, P < 0.05). We conclude that there was a trend of better overall survival in patients with IGF-1R+ tumours, and PRL < 20.0 ng/ml plasma when compared to patients with IGF-1R- tumours, and PRL > 20.0 ng/ml plasma. Further, IGF-1R negativity in conjunction with hyperprolactinemia could be used as an indicator of unfavourable prognosis in patients with Dukes B or C colon/rectal cancer.

Adult↗
PubMed1995

Expression of CD44 molecules and CD44 ligands during human thymic fetal development: expression of CD44 isoforms is developmentally regulated.

It has recently been recognized that CD44 comprises a large family of alternatively spliced forms. In the thymus, CD44 has been postulated to play an important role in immature T cell migration and maturation. In this paper, we have studied the expression of CD44 molecules and two CD44 ligands, hyaluronan (HA) and fibronectin (FN), during human thymic fetal development. We found that mAbs against all CD44 isoforms (A3D8 or A1G3) reacted with both thymic epithelial (TE) cells and thymocytes beginning at the time of initial colonization of the human thymus by hematopoietic stem cells at 8.2 weeks of fetal gestation. However, mAbs specific for splice variants of CD44 containing membrane-proximal inserts (11.24, 11.10 and 11.9) reacted only with terminally differentiated TE cells in and around Hassall's bodies beginning at 16-19 weeks of fetal gestation. Studies of differentiated versus undifferentiated TE cells in vitro confirmed the selective expression of CD44 variant isoforms on terminally differentiated TE cells. Expression of HA and FN was determined by fluorescence microscopy using either biotinylated-HA binding protein or an anti-FN mAb. We found that whereas FN was present throughout the human fetal thymus beginning at 8.2 weeks, HA was not present until 16 weeks of gestational age. These data demonstrate the differential expression of standard versus variant CD44 isoforms during thymic ontogeny and implicate CD44 interactions with ligands other than HA as important in the earlier stages of human thymus development.

Antibodies, Monoclonal↗
PubMed1995

Distribution of CD44 variant isoforms in human skin: differential expression in components of benign and malignant epithelia.

Expression of cell adhesion molecules regulates epithelial cell differentiation and organization of complex tissues such as skin. The CD44 family of adhesion molecules is generated by alternative splicing of up to 10 variant exons encoding inserts into the extracellular domain. Expression of CD44 variant exons has been correlated with metastatic potential of some epithelial malignancies. We studied the distribution of total and variant CD44 isoforms containing exons v4, v6, and v9 in normal skin, basal cell carcinoma, and in control tissues using immunohistologic assays. While normal epidermis and other stratified squamous epithelia reacted strongly with antibodies specific for standard CD44 (CD44S) and CD44 isoforms containing exons v4, v6, and v9, the epithelium of eccrine glands was reactive, often in a polarized distribution, only with antibodies specific for CD44S and isoforms containing exon v9. These studies suggest that differential expression of CD44 variant exons may be important in development and organization of epithelial structures within skin. Malignant cells in basal carcinoma tissues were found to have low reactivity with antibodies specific for CD44S or variant CD44 molecules. The low expression of CD44 molecules in basal cell carcinomas may play a role in the relatively low probability of metastasis of these neoplasms.

Antibodies, Monoclonal↗
PubMed1995

Characterization of a splice-site mutation in the gene for the LDL receptor associated with an unpredictably severe clinical phenotype in English patients with heterozygous FH.

We have identified a substitution of G to A in the first base pair of intron 3 in the LDL receptor gene of an English heterozygous familial hypercholesterolemia (FH) patient. Reverse transcription, amplification, and nucleotide sequencing of the LDL receptor mRNA from mononuclear blood cells showed both the normal mRNA and one that lacked the nucleotides encoded by exon 3, which codes for repeat 2 of the ligand-binding domain. The same mutant allele was identified in 2/200 unrelated FH patients from the London area and 4/77 from Manchester. Immunoblotting of cultured lymphoblasts from the index patient revealed the normal receptor protein and smaller amounts of a receptor protein with electrophoretic mobility consistent with a deletion of the 41 amino acid residues encoded by exon 3. Normal amounts of a similar protein were observed when the mutant cDNA was expressed in heterologous cells; this protein showed reduced binding affinity for LDL but bound apoprotein E-containing lipoproteins normally. Despite these and other observations that repeat 2 of the binding domain is relatively unimportant for receptor function in vitro, carriers of this allele exhibit a severe clinical phenotype, typical of FH. Thus, the relationship between genotype and phenotype in heterozygous FH is not always predictable.

Adult↗
PubMed1995

Comparison between serum levels of carcinoembryonic antigen, sialic acid and phosphohexose isomerase in lung cancer.

The identification and application of quantifiable tumor markers as adjuncts to clinical care is a story of both success and failure. The present study compared serum levels of carcinoembryonic antigen (CEA) with total sialic acid/total protein (TSA/TP) ratio and phosphohexose isomerase (PHI) in 192 untreated lung cancer patients as well as 80 age and sex matched controls (44 non-smokers and 36 smokers). CEA values were significantly raised (p < 0.001) in smokers as compared to the non-smokers; whereas, TSA/TP and PHI values were comparable between the two groups of the controls. All the biomarkers were significantly elevated (p < 0.001) in untreated lung cancer patients as compared to the controls. Receiver operating characteristic curve analysis revealed higher sensitivities of TSA/TP and PHI as compared to CEA at different specificity levels between 60% and 95%. Mean values of CEA, TSA/TP and PHI were higher in non-responders compared to the responders. The results indicate that TSA/TP and PHI are superior tumor markers than CEA for lung cancer patients.

Biomarkers, Tumor↗
PubMed1994

Characterization of a CD6 ligand(s) expressed on human- and murine-derived cell lines and murine lymphoid tissues.

CD6, a type I cell surface glycoprotein expressed predominantly by thymocytes and mature T lymphocytes, becomes phosphorylated on tyrosine residues following T cell activation and has been implicated as an accessory molecule in T cell activation. The purpose of this study was to identify cell lines and tissues which express CD6 ligand(s), determine the requirements for CD6 binding, and biochemically characterize the putative CD6 ligand(s). Binding studies with a CD6 immunoglobulin fusion protein, CD6-Rg, allowed the identification of a number of human cell lines which express a CD6 ligand(s). The binding to these cell lines was trypsin sensitive, in part required divalent cations, was blocked by an anti-CD6 mAb, and could be downregulated by tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma). Among the cell lines tested, the human breast carcinoma-derived cell line HBL-100 expressed the highest levels of CD6 ligand(s) and was used for immunoprecipitation studies. Following metabolic labeling, CD6-Rg immunoprecipitated glycoproteins of approximately 100, approximately 90, and approximately 45 kDa from HBL-100 cells. Using CD6-Rg we were able to show that murine thymus, lymph nodes, and skin express high levels of CD6 ligand(s) and that CD6-Rg bound to a murine thymic epithelial cell line and to cultured human epidermal keratinocytes.

Animals↗
PubMed1994

Assessing benefits of combining biochemical and immunological markers in patients with lung carcinoma.

Establishment of a simple biochemical index for diagnosis of cancer and management of patients with neoplastic diseases remains one of the important goals to be achieved in cancer research. The current investigation determined serum levels of carcinoembryonic antigen (CEA), total sialic acid (TSA) and lipid bound sialic acid (LSA) in 192 untreated lung cancer patients and compared with 80 age- and sex-matched controls (44 non-smokers and 36 smokers). The levels of all the markers were significantly elevated (P < 0.001) in lung cancer patients compared to the controls. CEA and LSA values were significantly raised (P < 0.001 and P < 0.01, respectively) in smokers compared to non-smokers. TSA and LSA values were more sensitive than CEA for diagnosis of lung cancer. Mean values of the three markers were higher in non-responders (n = 5) compared to the responders (n = 10). The results suggest that along with CEA, TSA and LSA might be included as routine parameters in lung cancer patients.

Biomarkers, Tumor↗
PubMed1994

Plasma prolactin in patients with colorectal cancer. Value in follow-up and as a prognosticator.

BACKGROUND: Preoperative plasma prolactin and carcinoembryonic antigen (CEA) levels were assessed to monitor disease recurrence and to identify low-risk and high-risk patients with Dukes B or C colorectal cancer. METHODS: Prolactin and CEA were estimated by radioimmunoassay method. Blood samples were collected preoperatively and sequentially thereafter from patients with colorectal cancer (N = 114); the samples were compared with samples from age-matched healthy control subjects (smokers and nonsmokers, N = 45). For rest of the analysis, patients with Dukes A disease (N = 7) were not included because of the small number. In monitoring recurrences, the criteria for positive test for the two markers was a continual increase in the marker level after an initial decrease or persistent high level of the marker. These were the indicators of relapse or no response to treatment. To determine the efficacy of the preoperative markers, the patients were grouped according to disease status at the end of 3 years, i.e., patients who had response to the treatment modalities (N = 52) and patients who later had progressive disease (N = 55). To determine the prognostic significance of preoperative marker levels, the patients were divided according to the cutoff levels (upper normal limits); for prolactin the cutoff level was 20.0 ng/ml plasma, and for CEA it was 5.0 ng/ml plasma. RESULTS: Both of the markers were significantly high in patients with colorectal cancer compared with the markers of their respective control subjects (P < 0.0001). In monitoring disease course, the predictive power of prolactin was 100%, whereas that of CEA was 66%. Prolactin showed a lead time of 2-3 months. Preoperative prolactin levels were significantly higher in patients who later had progressive disease (P < 0.001) than in patients who had response to the treatments. However, such an intergroup variation was not observed for CEA. Patients with preoperative levels of prolactin greater than 20.0 ng/ml had shorter overall survival times than did those with prolactin levels less than 20.0 ng/ml plasma; such a trend was not observed for patients with CEA levels less than 5.0 ng/ml and those with CEA levels greater than 5.0 ng/ml plasma. CONCLUSION: Prolactin is a better overall marker than is CEA in patients with Dukes B or C colorectal cancer. The authors recommend the use of plasma prolactin levels to help identify low-risk and high-risk patient subgroups so that high-risk patients may be followed up more intensely and treated accordingly. Hyperprolactinemic patients with Dukes B or C disease have shortened survival time.

Adult↗
PubMed1994

Prolactin: its role in advanced tongue cancer.

Serum prolactin was measured pretherapeutically and sequentially thereafter using immunoradiometric assay method in 37 male patients with advanced tongue cancer and compared with 23 healthy, age-matched controls. Prolactin levels were correlated with age, various clinicopathologic parameters, overall survival, and patients with response and those with progressive disease. Patients with advanced tongue cancer had higher prolactin levels than controls (P < 0.02), but intergroup variation in prolactin was not observed when considering the age, site of the lesion, disease stage, histologic grade, and keratin. Of the patients, 30% had hyperprolactinemia (prolactin > 15.0 ng/ml). To assess the prognostic significance of pretherapeutic prolactin level, the patients were divided according to the cutoff level of prolactin (15.0 ng/ml). Hyperprolactinemic patients had more unfavourable prognosis than patients with prolactin < 15.0 ng/ml (X2 = 2.91, df = 1, P < 0.0037). In monitoring disease course, patients who responded to treatments had decreased prolactin levels at the end of 18 months as compared to their pretherapeutic levels (P < 0.01). In patients who subsequently developed progressive disease within 18 months, prolactin levels reduced initially at response, whereas with disease progression, prolactin levels increased significantly (P < 0.05). The positive and negative predictive value of prolactin was 100%. Immunohistochemical localization confirmed the ectopic production of prolactin by tongue tumors. In conclusion, our data indicate that hyperprolactinemia may be an independent predictor of short-term prognosis; circulating prolactin may be used as a marker for monitoring disease course in patients with advanced tongue cancer, and prolactin is produced ectopically by tongue tumors.

Adult↗
PubMed1994

Tumor markers in patients with advanced breast cancer as prognosticators: a preliminary study.

A retrospective study was performed on 69 breast cancer patients (stage II, N = 18; advanced disease, N = 51) in order to assess the prognostic value of circulating prolactin (PRL), CEA, CA 15-3, insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF) by RIA/IRMA. These markers were compared with short-term prognosis (two years). Significant difference was observed only for PRL ( < 20.0 ng/ml vs. > 20.0 ng/ml), which provide an independent predictor of short-term prognosis in advanced breast cancer.

Biomarkers, Tumor↗
PubMed1994

Characterization and tissue-specific expression of the human 'very low density lipoprotein (VLDL) receptor' mRNA.

A cDNA has been isolated from human heart that is homologous to a member of the low density lipoprotein (LDL) receptor gene family recently identified in rabbit. It was named the very low density lipoprotein (VLDL) receptor, although its physiological function is not yet known. The predicted human protein shows 97.4% sequence homology to the rabbit protein, much more than the approximately 75% observed between their LDL receptor proteins. The sequence is also highly conserved in the hamster and the African green monkey. The mRNA was identified as a 3.9 kb transcript by Northern blotting in Hep G2 cells, cultured arterial smooth muscle cells and human skin fibroblasts, where its level was unaffected by sterols. The mRNA was not detected in EBV-lymphoblasts or in monocyte-macrophages by Northern blotting or by RT-PCR. In human tissues in vivo, the mRNA was expressed predominantly in heart and skeletal muscle, and also in ovary and kidney, but not in the liver. Although the 3.9 kb mRNA was the major transcript, a larger variant of 5.2 kb was also detectable and was predominant in skeletal muscle. Amplification of the mRNA from cultured human cells also revealed a potential splice variant that lacked 84 bp coding for a region equivalent to the O-linked sugars domain of the LDL receptor. It was a minor component in most cell types, but was predominant in Hep G2 cells.

Amino Acid Sequence↗
PubMed1994

Familial hypercholesterolemia in China. Identification of mutations in the LDL-receptor gene that result in a receptor-negative phenotype.

Familial hypercholesterolemia (FH), caused by many different mutations in the low-density lipoprotein (LDL)-receptor gene, invariably leads to severe premature coronary heart disease (CHD) in homozygous individuals. Heterozygous FH patients are less severely affected but are still at increased risk of CHD in most populations. Although FH homozygotes in China are affected similarly to those elsewhere, heterozygotes are not detected in the general population and obligate heterozygotes are often not hypercholesterolemic by Western standards. Mutations in the LDL-receptor genes of 10 homozygous FH patients from the Jiang-su province of China and their heterozygous parents were analyzed. These include one large and two minor deletions and eight point mutations: four are predicted to introduce a premature stop codon, five to result in a single amino acid substitution or deletion, and one to produce a protein with an abnormal cytoplasmic tail. Expression of the mutant LDL-receptor cDNAs in vitro confirmed that these mutations impaired LDL-receptor function and that several would cause a receptor-negative phenotype. Thus, the lack of clinical expression in obligate FH heterozygotes is not due to unusually "mild" mutations in the LDL-receptor gene, and other genetic or environmental factors must therefore be important in determining phenotypic expression.

Adolescent↗