Biomedical subjects

D D Patel

Publications and source records attributed to D D Patel.

At least 127 records · Page 7Linked to original sources

PubMed1994

Erythrocytic glutathione in cystic fibrosis. A possible marker of pulmonary dysfunction.

To evaluate the role of red blood cell (RBC) antioxidants as clinical markers of oxidative exposure, we measured RBC glutathione (GSH) concentrations in 32 adult patients with cystic fibrosis (CF), and 8 healthy age-matched control subjects. We chose patients with CF because this disease is characterized by severe bronchial inflammation and marked oxidant-antioxidant imbalance. Although the GSH concentration of the two study groups was not significantly different, the RBC GSH concentration of patients with CF had a greater variability (p = 0.01) and was also inversely and significantly correlated to tests of pulmonary function (p < 0.05). These data indicate a large and significant interindividual variability of erythrocytic antioxidants in patients with CF, with a compensatory, but probably inadequate, increase in patients with more severe respiratory deterioration. Red blood cell GSH concentration may thus provide a biologic marker for disease severity and a rationale for antioxidant manipulation in these patients.

Adult↗

PubMed1994

Partial duplication of the EGF precursor homology domain of the LDL-receptor protein causing familial hypercholesterolemia (FH-Salerno).

A novel mutation of low density lipoprotein (LDL)-receptor gene was found in an Italian family hypercholesterolemia (FH) patient during a screening of 300 FH patients. The proband as well as her daughter were found to be heterozygotes for the mutation. Binding, internalization, and degradation of 125I-labeled LDL by the proband's fibroblasts were reduced to approximately 50% compared to values found in control cells. DNA analysis by Southern blotting showed that the mutant allele was characterized by an insertion of about 10 kb, which resulted from a duplication of exons 9-14 of the LDL-receptor gene. In addition, Northern blot analysis of the proband's RNA showed, besides the normal sized LDL-receptor mRNA (5.3 kb), an additional mRNA of about 6.2 kb. The junction between exon 14 and the duplicated exon 9 was amplified by polymerase chain reaction (PCR) from the cDNA. The sequence of the amplified fragment showed that exon 14 joined the duplicated exon 9 without changing the reading frame. The derived amino acid sequence indicated that the mutated receptor protein had a partial duplication of the EGF precursor homology domain. Ligand and immunoblotting revealed that proband's fibroblasts contained one-half of the normal amount of LDL-receptor protein (molecular mass 130 kDa) and an abnormally large receptor of approximately 160 kDa. The amount of this abnormal receptor as detected by two monoclonal antibodies (10A2 and 4B3) was found to be approximately 30% that of the normal LDL-receptor present in the same cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1994

Can plasma prolactin predict tamoxifen resistance in patients with advanced breast cancer?

The antiestrogen tamoxifen (TAM) is an effective therapy for advanced breast cancer. However, its use is limited by the eventual development of acquired TAM resistance in many patients. There is now strong evidence to suggest that prolactin plays an important role in advanced breast cancer. We have measured plasma prolactin (PRL) and estrogen-receptor (ER) and progesterone-receptor (PR) in post-menopausal patients with breast cancer (Stage III, n = 44). The blood samples were collected pre-operatively and sequentially thereafter for a minimum period of 3 years or until the death of the patients. The ER and PR were estimated in breast tumor samples by dextran-coated charcoal (DCC) method. The patients were treated with surgery and radiotherapy followed by TAM (10 mg, 1 BD). Based on the response to treatments, the patients were divided into two groups: (1) TAM sensitive (n = 19) and (2) TAM resistant (n = 25). In the TAM sensitive group, patients responded to the treatment and did not develop progressive disease within a period of 3 years. On the contrary, in the group of TAM resistant, patients developed progressive disease within a period of 3 years. The development of progressive disease clearly indicated TAM resistance. Plasma PRL correlated well with the disease progression. This study clearly demonstrated that plasma prolactin accurately indicated the response and development of resistance to TAM in patients with advanced breast cancer.

Breast Neoplasms↗

PubMed1994

Circulating prolactin and tumoral prolactin receptors in men with tongue cancer: a preliminary study.

Pre-therapeutic circulating prolactin levels and tumoral prolactin receptors (PRLR) were determined in 25 male patients with tongue cancer. The patients were divided into PRLR positive (PRLR+) and PRLR negative (PRLR-) groups. The overall survival was statistically non-significant between these two groups of PRLR as well as when considering 2% as the cut-off level. Moreover, no correlation was observed between PRLR status and clinicopathologic prognosticators. Furthermore, patients with < 2% PRLR had significantly higher levels of circulating prolactin than their counterparts (P < 0.05). Patients with PRLR- tumors having hyperprolactinemia (prolactin > 15.0 ng/ml) had unfavourable overall survival (chi 2 = 4.08, df = 1, P < 0.04) than those with normoprolactin (prolactin < 15.0 ng/ml). From this pilot study, it seems that PRLR negativity with hyperprolactinemia could be used as an independent predictor of short-term prognosis in cancer tongue patients.

Carcinoma, Squamous Cell↗

PubMed1994

Levels of circulating peptide and steroid hormones in men with lung cancer.

Levels of circulating peptide (FSH, LH, prolactin, ACTH, calcitonin, gastrin and insulin-like growth factor-1 [IGF-1]) and steroid (estradiol, progesterone, DHEA-S and testosterone) hormones were estimated by radioimmunoassay (RIA) and immunoradiometric assay (IRMA) in male patients with lung cancer (n = 37) pre-therapeutically and compared with 25 age matched healthy controls. In this retrospective study, FSH, LH, prolactin, ACTH, calcitonin, gastrin and IGF-1 were significantly higher with concomitant lower levels of DHEA-S and testosterone, while the difference was statistically non-significant for estradiol and progesterone in patients with lung cancer when compared with controls. Early stage patients (Stage II) exhibited higher levels of gastrin as compared to advanced stage patients (Stages III and IV). It is suggested that hormonal imbalance might play an important role in the development and progression in male patients with lung cancer.

Adrenocorticotropic Hormone↗

PubMed1993

A mutation and an antibody that affect chemical cross-linking of low-density lipoprotein receptors on human fibroblasts.

Treatment of normal fibroblasts with the bifunctional cross-linking reagent DTSSP [3,3'-dithiobis(sulphosuccinimidylpropionate)] at 4 degrees C converted approximately 40% of the cell-surface low-density lipoprotein (LDL) receptors into a high-M(r) form, thought to represent receptor dimers. Preincubation of the cells with anti-(LDL receptor) monoclonal antibody 10A2 increased the proportion of surface receptors in the high-M(r) form after treatment with DTSSP at 4 degrees C to over 70%. Preincubation with LDL did not affect the proportion cross-linked, but prevented the increase produced by antibody 10A2. Cross-linking at 37 degrees C was less efficient than at 4 degrees C and was not affected by preincubation with antibody 10A2. Surface LDL receptors on fibroblasts from the homozygous familial hypercholesterolaemic subject MM were not cross-linked by DTSSP, confirming that the mutation had produced a change in the conformation of the receptor molecule. Taken together, the results suggest that normal LDL receptors on at least one region of the surface membrane may be loosely associated in some form of multimeric array which alters its alignment differently in response to antibody 10A2 and to cooling. Mutations that alter the tertiary structure of the receptors could affect LDL binding by disturbing the arrangement of the array.

Antibodies, Monoclonal↗

PubMed1993

Cell adhesion molecules involved in intrathymic T cell development.

During stem cell migration to the thymus, intrathymic maturation of T cells, and emigration of mature T cells out of the thymus, intercellular interactions of developing T cells with a myriad of cell types are required for normal T cell development. Intercellular interactions of T cell precursors with endothelial cells, thymic epithelial cells, fibroblasts, thymic macrophages and dendritic cells are all mediated by adhesion molecules on immature T cells binding to ligands on thymic microenvironment cells. While many receptor-ligand interactions that are important in intrathymic T cell development are known, the adhesion molecules that are important for migration of T cell precursors to the thymus and for emigration of mature thymocytes from the thymus are poorly understood. An emerging concept is that select adhesion molecules at discrete stages of T cell maturation participate in and regulate the complex processes of T cell development.

Animals↗

PubMed1993

Cholesterol-lowering drug therapy in a patient with receptor-negative homozygous familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is caused by mutations in the gene for the low density lipoprotein (LDL) receptor. It is generally believed that homozygous FH patients do not respond well to lipid-lowering drug therapy with inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase because they cannot respond to an increased demand for hepatic cholesterol by up-regulation of LDL-receptor activity. In this paper we show that serum cholesterol in a homozygous FH patient with a receptor-negative LDL-receptor phenotype was reduced by 30% after treatment with simvastatin alone and by a further 11% with simvastatin in combination with probucol and nicotinic acid. The patient was a true homozygote, with two identical alleles of the LDL receptor gene in which a previously undescribed point mutation in exon 11 introduces a premature termination codon at residue 540 in the protein; the mutant protein is predicted to be truncated in the domain with homology to the epidermal growth factor precursor. Cultured cells from the patient were unable to bind, internalise or degrade LDL by the receptor pathway and there was no immunodetectable LDL receptor protein in the cells. Thus the lipid lowering effect of simvastatin in this individual must involve mechanisms other than stimulation of LDL receptors.

Adolescent↗

PubMed1993

Circulating markers and growth factors as prognosticators in men with advanced tongue cancer.

A retrospective study was performed on 52 advanced tongue cancer patients (stages III + IV) in order to assess the prognostic value of circulating prolactin, tissue polypeptide-specific antigen (TPS), insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF). These markers were correlated with short-term prognosis (2 years). The advanced tongue cancer patients had significantly elevated levels of prolactin (p < 0.02), TPS (p < 0.05) and EGF (p < 0.01) and low levels of IGF-1 when compared to controls. The patients were grouped according to the commonly used cut-off levels of these markers. A significant difference in survival was observed only between two subgroups of prolactin (< 15.0 and > 15.0 ng/ml; p < 0.001). Hence, prolactin may provide an independent predictor of short-term prognosis in patients with advanced tongue cancer.

Biomarkers, Tumor↗

PubMed1993

Experience with penile venous surgery.

Venogenic impotence was detected in 37 out of 141 patients who attended our clinic with a complaint of erectile dysfunction. Eighteen patients presented with primary impotence and the rest had progressive secondary impotence. All 37 patients have shown partial or poor response to 60 mg of intracavernosal papaverine. The corporovenous leak (CVL) was diagnosed on the careful workup of dynamic pharmacocavernosometry and cavernosography. Concomitant arterial cause was noted in 10% cases on the basis of penile duplex Doppler ultrasound study. 24 patients in the age group of 23-60 years underwent the penile venous surgery. The CVL was noted in the deep dorsal vein (23 cases), cavernous vein (16) and in the crural vein (2). The operation consisted of deep dorsal vein (DDV) ligation and excision with all tributaries (8 cases) or DDV ligation and excision+cavernous vein ligation (13 cases), through an infrapubic curvilinear incision. One patient had crural vein ligation and corporoplasty through a perineal incision, one had direct corporeal revascularization for associated arteriogenic impotence with venous leak and another had distal spongiolysis and closure of a corporospongiosal shunt. The results were excellent in 11 cases, improved in 6 and 7 had failures. Surgical intervention is effective in CVL in selected cases but limiting factors in the form of increasing age, concomitant arteriogenic cause, significant crural leak, missing tributaries, recurrent venous leak and unknown factors may also be present to prevent total cure.

Adult↗

PubMed1993

Prognostic significance of plasma prolactin in breast cancer: comparison with the expression of c erb B-2 oncoprotein.

Having established prolactin to be an indicator of disease progression and hyperprolactinemia as an independent predictor of short term prognostication, we have in this report compared plasma prolactin with the expression of c erb B-2 oncoprotein, ER and PR. c erb B-2 oncoprotein, ER and PR are determinants of breast cancer biology. This is a retrospective study of 47 breast cancer patients. When patients were grouped according to the stage of the disease, plasma prolactin was higher in patients with advanced disease than those with stage II disease. The patients were sub-grouped according to prolactin < 20.0 ng/ml and > 20.0 ng/ml. The expression of c erb B-2, ER and PR did not differ in these two sub-groups. The overall survival differed significantly between the two sub-groups of prolactin. The patients were sub-grouped according to c erb B-2 positivity or negativity, there was no significant difference in survival. c erb B-2 expression did not differ between the three grades of the tumor, nodal and receptor positivity or negativity. Hence, the present study reinforces the positive association between hyperprolactinemia and unfavourable prognosis and finds c erb B-2 expression as a weak prognosticator in advanced breast cancer patients.

Biomarkers, Tumor↗

PubMed1993

Correlation of steroid receptors in synchronous tissues with survival in breast cancer patients.

Estrogen and progesterone receptors (ER and PR) were estimated in 129 synchronous (primary and metastatic lymph node) breast cancer tissues, of which 40% were premenopausal and 60% were postmenopausal. ER and PR accordance was seen in 68% and 70% patients, and ER and PR discordance was seen in 32% and 30%, respectively. The mean level of ER in patients having ER accordance was higher in responders than in nonresponders. In patients having steroid receptors in accordance, there was a trend towards gain of receptors (type II) in responders, and loss of receptors (type I) in nonresponders. In ER discordant cases 48% were of type I while in PR discordant cases 46% were of type I. In postmenopausal patients, survival was lower in patients showing accordance than in those showing discordance. In nonresponders showing loss of receptors in lymph node, the survival was shorter than in those who showed gain of receptors in lymph node. No such trend was seen in premenopausal patients. Our study suggests that in postmenopausal patients, survival was better related to ER accordance than ER discordance and PR accordance or discordance. However, a larger patient series is needed for confirmation.

Adult↗

PubMed1992

Site-specific RNA cleavage generates the 3' end of a poxvirus late mRNA.

The cowpox virus late mRNAs encoding the major protein of the A-type inclusions have 3' ends corresponding to a single site in the DNA template. The DNA sequence of the Alu I-Xba I fragment at this position encodes an RNA cis-acting signal, designated the AX element, which directs this RNA 3' end formation. In cells infected with vaccinia virus the AX element functions independently of either the nature of the promoter element or the RNA polymerase responsible for generating the primary RNA. At late times during virus replication, vaccinia virus induces or activates a site-specific endoribonuclease that cleaves primary RNAs within the AX element. The 3' end produced by RNA cleavage is then polyadenylylated to form the 3' end of the mature mRNA. Therefore, the poxviruses employ at least two mechanisms of RNA 3' end formation during the viral replication cycle. One mechanism, which is operative at early times in viral replication, involves the termination of transcription [Rohrmann, G., Yuen, L. & Moss, B. (1986) Cell 46, 1029-1035]. A second mechanism, which is operative at late times during viral replication, involves the site-specific cleavage of primary RNAs.

Base Sequence↗

PubMed1992

Comparison of plasma prolactin and CEA in monitoring patients with adenocarcinoma of colon and rectum.

Plasma prolactin (PRL) and carcinoembryonic antigen (CEA) were measured by radioimmunoassay in 74 patients with adenocarcinoma of colon and rectum. The markers were correlated with disease stage, histological grade and progression/remission of disease. The circulating preoperative median PRL and CEA levels were significantly higher in colorectal cancer patients than in their respective controls. PRL was elevated in all Dukes stages and in all histological grades of the tumour whereas the rise in CEA was more pronounced in Dukes D. Out of 74 patients, 29% (21/74) developed recurrent disease and 31% (23/74) responded to the treatment. With regard to monitoring recurrence(s), the predictive value of PRL was 94% which was significantly greater than that of CEA which was only 62%. In patients who developed liver metastases PRL remained elevated whereas CEA showed more than 100-fold increase. Therefore, we feel that CEA is a better marker for monitoring patients who developed liver metastases. From our results, we suggest that PRL can be used as a better overall marker for detecting recurrence(s) in patients with colorectal adenocarcinoma.

Adenocarcinoma↗

PubMed1992

Characterization of two new point mutations in the low density lipoprotein receptor genes of an English patient with homozygous familial hypercholesterolemia.

Two new point mutations have been detected in the low density lipoprotein (LDL) receptor gene of a patient with a clinical diagnosis of homozygous familial hypercholesterolemia (FH). The patient is a compound heterozygote, in whom the mutant allele inherited from his English father has a single base substitution of A for G in exon 3, changing the codon for residue 80 in the mature protein from glutamic acid to lysine. The mutant allele inherited from his mother, who is of Irish origin, has a single base pair deletion in the codon for residue 743 in exon 15 that causes a frameshift and introduces a new stop codon in the adjacent position. The glu80 to lys mutation results in a transport-defective phenotype and a mature protein that migrates abnormally slowly on nonreduced SDS-PAGE, but normally under reducing conditions; this was confirmed by site-directed mutagenesis and expression in vitro. The deletion in exon 15 results in a null phenotype in which the putative truncated receptor protein cannot be detected in cultured skin fibroblasts and the amount of mRNA derived from the allele is reduced. The glu80 to lys mutation was found in a further five unrelated individuals in a sample of 200 FH patients from the London area and in 11 from a sample of 77 FH patients from Manchester. Haplotype analysis suggested that all the patients had inherited this allele from a common ancestor. The deletion in exon 15 was not found in the London sample, nor in any unrelated individuals in the Manchester sample.

Alleles↗

PubMed1992

Endocrine status in stage II vs. advanced premenopausal and postmenopausal breast cancer patients.

Circulating preoperative levels of DHEA-S, androstenedione and SHBG were measured in 40 premenopausal and 49 postmenopausal breast cancer patients, and in 30 and 15 age-matched healthy controls, respectively. Moreover, the levels of LH, FSH, prolactin, estradiol, progesterone, testosterone, DHEA-S, androstenedione and SHBG of Stage II breast cancer patients were compared with advanced patients and also with controls. In premenopausal patients the levels of steroid hormones were significantly low whereas those of peptide hormones were significantly high. On the contrary, in postmenopausal patients, except DHEA-S, all other hormones were significantly elevated in comparison with controls. In premenopausal patients, DHEA-S, androstenedione, estradiol, progesterone, and testosterone decreased as stage advanced with concomitant increase of SHBG, LH, FSH and prolactin when compared with hormone levels of Stage II patients. In postmenopausal advanced breast cancer patients, when compared with Stage II patients, the levels of SHBG, LH, FSH, and prolactin increased significantly, while DHEA-S, androstenedione, estradiol, and progesterone decreased as stage advanced.

Androstenedione↗

PubMed1992

Estrogen and progesterone receptor status of primary breast cancer: relationship with the pattern of first metastasis and survival.

Estrogen (ER) and progesterone receptor (PR) contents in primary tumors from 127 advanced breast cancer patients were measured by DCC method. The patients were followed for 2 years and the prognostic value of the receptor levels was evaluated and compared with other tumor and patient characteristics. No relation was found between receptor levels and tumor, first relapse site as well as short-term survival (2 years) which might be due to the advanced stage of disease at diagnosis.

Adult↗

PubMed1992

Endocrine function in premenopausal and postmenopausal advanced breast cancer patients treated with CMF or tamoxifen.

The effect of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) or tamoxifen treatment on endocrine function was investigated in premenopausal and postmenopausal breast cancer patients. CMF therapy resulted in ovarian failure but pituitary and adrenal functions were unaffected in premenopausal patients. Although amenorrhea was achieved within two to five months in older patients, younger patients required large cumulative doses of cytotoxic drugs to exhibit ovarian dysfunction. CMF therapy had no effect on hormonal levels in postmenopausal patients indicating that in this group therapeutic response is not mediated via the endocrine system. On the other hand, tamoxifen therapy in postmenopausal patients resulted in hyperestrogenemia.

Adult↗