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P Mehta

Publications and source records attributed to P Mehta.

At least 19 recordsLinked to original sources
PubMed1992

Co-purification of 130 kD nitric oxide synthase and a 22 kD link protein from human neutrophils.

The synthesis of nitric oxide (NO) from L-arginine has been demonstrated in several cell types. Both constitutive and inducible forms of NO synthase have been described in different cells. We purified the constitutive form of NO synthase enzyme in human neutrophils using a two-column procedure. Crude 100,000g supernatant of human neutrophils was passed through a 2'-5'-ADP-agarose column followed by a DEAE-Bio-Gel A anion exchange column. NO synthase enzyme migrated as a single band (MW approximately 130,000) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Its activity was dependent upon nicotinamide adenine dinucleotide phosphate (NADPH) and (6R)-tetrahydro-L-biopterin (BH4). In addition, flavin adenine dinucleotide (FAD) was also found to be essential for its maximal activity. A second NADPH, FAD-dependent component (MW approximately 22kD) was also found consistently on the SDS-PAGE gel. These observations suggest co-regulation between NO synthase enzyme and this NADPH, FAD-dependent component, which may be associated with the superoxide radical generating system.

Amino Acid Oxidoreductases↗
PubMed1992

Tumor-associated antigen 43-9F is of prognostic value in squamous cell carcinoma of the lung. A retrospective immunohistochemical study.

BACKGROUND: Squamous cell lung carcinoma (SLC), the most frequent type of lung cancer, generally is treated surgically and its prognosis is poor. The only current clinically useful prognostic criterion is lymph node staging (TNM classification). Expression of a novel tumor-associated carbohydrate epitope Gal beta 1-3[Fuc alpha 1-4]GlcNAc beta 1-4[Fuc alpha 1-3]GlcNAc beta 1-3 Gal beta 1-4Glc identified by the 43-9F monoclonal antibody (MoAb) is associated with the growth pattern of SLC cell lines in athymic mice and in vitro. This implies that the 43-9F epitope may be related to tumor progression in patients with SLC and that, as such, it could be of prognostic value. METHODS: Primary tumor specimens from 231 patients with lung carcinoma (130 with SLC, 64 with adenocarcinoma, 10 with small cell carcinoma, 16 with large cell carcinoma, and 11 with adenosquamous carcinoma) were examined by immunohistochemical studies on formalin-fixed, paraffin-embedded tissue samples for immunoreactivity with an MoAb to the 43-9F antigen. Univariate and step-wise Cox regression analyses were used to compare survival time by histopathologic diagnosis, smoker status, TNM classification, and type of surgical treatment. RESULTS AND CONCLUSIONS: Patients with 43-9F epitope-positive SLC tumors had a significantly (P less than 0.01) better prognosis than patients with epitope-negative tumors. In contrast, no association was seen between 43-9F epitope expression and survival time for patients with lung adenocarcinomas. Further, the prognostic value of 43-9F expression in SLC was found to be superior to the N-classification with the added advantage that it requires access only to primary tumor tissue and thus is available before therapy.

Adult↗
PubMed1992

A study of toxicity and comparative therapeutic efficacy of vindesine-prednisone vs. vincristine-prednisone in children with acute lymphoblastic leukemia in relapse. A Pediatric Oncology Group study.

Vindesine (des-acetyl Vinblastine) is a synthetic derivative of vinblastine, and was produced with the hope that it would have less neurotoxicity and hematopoietic toxicity than other vinca alkaloids. Phase I and II studies also demonstrated significant activity in lymphoid malignancies, especially Acute Lymphoblastic Leukemia (ALL). The present study was designed to compare therapeutic effectiveness of twice weekly vindesine (2 mg/M2/dose) plus Prednisone (60 mg/M2/dose) (Treatment 1) to weekly Vincristine (2 mg/M2/dose) plus Prednisone (60 mg/M2/day) (Treatment 2). All patients were less than 21 years of age, and had documented bone marrow relapse (blast count > 25%). In 39 patients presumed sensitive to vincristine, there were 11 complete responses out of 20 patients (55%) randomized to receive vindesine/prednisone and 7 complete responses out of 19 patients (37%) treated with Vincristine/Prednisone. In 37 patients resistant to vincristine, there were 7 complete responses (19%). Vindesine was more toxic than Vincristine. Major toxicities of vindesine included paraesthesias, peripheral neuropathy and ileus. Vindesine hematological toxicity appeared greater, but such toxicity is hard to assess in patients with bone marrow disease. In this study, vindesine and vincristine had similar efficacy, but vindesine use was associated with more toxicity.

Adolescent↗
PubMed1992

Effect of diltiazem on norepinephrine-induced acute left ventricular dysfunction.

The present study has examined the role of diltiazem as a protective agent in a canine model of norepinephrine cardiotoxicity. Effects of diltiazem, 20 micrograms/kg/min x 5 min pretreatment followed by 10 micrograms/kg/min x 90 min, or saline infusion were examined at baseline and 1 h after infusion of norepinephrine, 4 micrograms/kg/min for 90 min, in closed-chest anesthetized dogs. Left ventricular function was assessed by equilibrium radionuclide angiogram and two-dimensional echocardiogram. In 7 saline experiments, hypotension and increased heart rate were observed at 1 h post infusion. In the diltiazem-treated group (n = 7), mean arterial pressure and heart rate were unchanged. In the saline group, left ventricular ejection fraction fell from 0.50 +/- 0.04 to 0.28 +/- 0.04. Left ventricular ejection fraction was unchanged in the diltiazem-treated group: 0.52 +/- 0.03 to 0.55 +/- 0.07. Left ventricular end-diastolic volume was increased at 1 h post infusion in saline controls but not in the diltiazem-treated group. Measurement of fractional shortening from two-dimensional echocardiograms also indicated left ventricular dysfunction in the saline but not diltiazem-treated groups. Left ventricular end-systolic wall stress following norepinephrine infusion was significantly increased in the saline but not diltiazem-treated groups: 122.7 +/- 18.7 vs 67.6 +/- 19.7 g/cm2, respectively. In dogs receiving saline without norepinephrine infusion, no significant changes occurred over the course of the experiment. Histologic examination showed mild contraction band necrosis in saline controls but not in sham saline dogs. Diltiazem showed intermediate histologic evidence of injury, which was not further quantified. This study suggests that effects of norepinephrine on left ventricular function in the canine model of norepinephrine cardiotoxicity may be largely due to increased wall stress following a prolonged increase in afterload. Diltiazem pretreatment afforded significant protection of left ventricular function.

Animals↗
PubMed1992

Modulation of vascular tone by endothelin-1: role of preload, endothelial integrity and concentration of endothelin-1.

1. Endothelin-1 (ET-1) has been shown to exert both arterial relaxant and constrictor effects. To examine the mechanisms of these divergent effects, rat aortic rings were suspended in an organ bath (baseline preload, 5 g) and exposed to ET-1 (10(-11) to 10(-7) M). ET-1 contracted these rings in a concentration-dependent fashion. 2. When aortic rings were contracted with noradrenaline (NA) to 1 g of tension, ET-1 caused further contraction of these rings. In rings precontracted to 2 to 4 g of tension, low concentrations of ET-1 (10(-11) to 10(-9) M) caused a significant relaxation, but high concentrations (greater than or equal to 5 x 10(-9) M) caused a marked contraction, indicating both relaxant and contractile effects of ET-1 depending on the preload and ET-1 concentration. 3. To determine the mechanism of ET-1-induced relaxation, aortic rings were pretreated with the cyclo-oxygenase inhibitor indomethacin, NG-monomethyl-L-arginine (L-NMMA) an inhibitor of synthesis of endothelium-derived relaxing factor (EDRF), or oxyhaemoglobin (Hb) which decreases the activity of EDRF, prior to their exposure to ET-1. Both indomethacin and L-NMMA markedly (P less than 0.01) attenuated ET-1-induced relaxation, whereas Hb totally abolished it. Removal of the endothelium from aortic rings also abolished ET-1-mediated relaxation. 4. The relaxant effect of ET-1 in NA-precontracted rings was associated with marked accumulation of guanosine 3':5'-cyclic monophosphate (cyclic GMP), whereas ET-1-induced contraction of quiescent rings was not. 5.In manually stretched rings (4 g of tension), ET-l caused only concentration-dependent contraction, but no cyclic GMP accumulation.6. Thus, ET-1 contracts rat aortic rings with intact endothelium and those which are passively stretched. However, stimulation of rat aortic rings with NA to modest tension alters the contractile effect of ET-1 to a potent relaxant effect. The ET-l-mediated relaxation in this setting appears to be endothelium-dependent and is related to release of both cyclo-oxygenase products and EDRF.

Animals↗
PubMed1992

[The immunohistochemical determination of hormonal receptors in breast cancer. A retrospective study in 322 cases].

A study of 322 patients with infiltrating ductal carcinoma of the breast, followed from 6 to 20 years, is presented. Pathological characteristics including immunohistochemical determinations of estrogen and progesterone receptors are shown, as well as interrelations of the different factors between themselves and with the follow up. Results showed significant relations between positive estrogen receptors and low nuclear grade (p < 0.001), histological low grade (p = 0.06) and positive progesterone receptors (p = 0.001). In addition, progesterone receptors were associated with stage I (p = 0.02); tumors with less than 2 cm in diameter (p = 0.01); low nuclear grade (p < 0.001) and positive estrogen receptors (p < 0.001). The univariate Cox regression analysis of prognostic factors revealed an association between positive lymph nodes and high nuclear grade with a more frequent tumoral recurrence. On the other hand, overall survival was significantly affected by cases in stage II, positive lymph nodes, tumors with diameter greater than 2 cm, and high nuclear grade. Stepwise Cox regression analysis showed that a high nuclear grade, positive lymph nodes and absence of estrogen receptor, were associated with a higher risk for recurrence and that tumor size and the state of lymph nodes were predictive for overall survival. This paper demonstrates that histochemical determination of hormonal receptors is useful because together with other known prognostic factors it contributes to a better management of patients with breast carcinoma.

Adult↗
PubMed1992

Immune electron microscopic characterization of monoclonal antibodies to Alzheimer neurofibrillary tangles.

Characterization of eleven monoclonal antibodies (MAbs), raised to isolated sodium dodecyl sulfate (SDS)-treated Alzheimer's neurofibrillary tangles (ANT), has revealed the presence of at least two different epitopes. MAbs were tested for reactivity to ubiquitin and paired helical filaments (PHF) isolated by three different procedures. The effect of protease and/or alkaline phosphatase pretreatment on the reactivity of the MAbs with isolated PHF was also examined. All MAbs that had reacted strongly in the ELISA with sonicated SDS-treated ANT also immune decorated isolated PHF to varying degrees. Two MAbs exhibited a high reactivity to PHF: 3-39 and 5-25. MAb 3-39 was found to recognize a protease sensitive epitope. In contrast MAb 5-25 was found to consistently decorate isolated PHF in all preparations and exhibited a strong reactivity to ubiquitin, and the epitope in isolated PHF was not protease sensitive. Thus structural PHF after protease treatment and detergent treatment contain an antigenic site that is present in ubiquitin.

Alzheimer Disease↗
PubMed1991

Purification and tissue level of the beta-amyloid peptide precursor of rat brain.

The beta-amyloid peptide precursor (beta-APP) exists in brain tissue as a membrane-associated protein extractable with 1% Triton X-100. beta-APP has been purified to near homogeneity by the following procedure: 1) anion exchange chromatography, 2) affinity chromatography on heparin agarose, and 3) immunoaffinity adsorption on matrix-bound antibodies directed to a synthetic peptide corresponding to the last 24 amino acids of the cDNA derived amino acid sequence of beta-APP. Conditions were chosen to minimize denaturation of the protein. The identity of the protein was confirmed by its immunoreactivity with antisera directed to five subsequences derived from the cDNA sequence. The amino-terminal sequence of beta-APP was found to be Leu-Glu-Val-Pro-Thr-Asp-Gly-Asn-Ala-Gly-Leu-Leu-Ala-Glu-Pro, which commences at residue 18 of the cDNA-derived primary structure. The procedure resulted in a 2000-fold purification of beta-APP. The purified protein migrated on polyacrylamide gels as a doublet of apparent molecular mass 100-120 kDa, although the predicted molecular mass of its constituent amino acids is 76 kDa. beta-APP clearly behaves anomalously in gel electrophoresis. The beta-APP content of rat brain amounted to 46 micrograms/g tissue. The half-life of the protein was calculated to be about 10 h, which is 30 times as long as that observed by others in transfected PC-12 cells. We conclude that transfected cell systems may not be adequate models for beta-APP processing.

Amino Acid Sequence↗
PubMed1991

Studies on the distribution of cellular myosin with antibodies to isoform-specific synthetic peptides.

Antisera were produced against two synthetic peptides having sequences specific for cellular myosin heavy chains from human macrophages (peptide IIA) and bovine brain (peptide IIB). Immunoblots of tissue extracts were made with these antibodies, and they showed that mammalian cells have at least three distinct cellular myosin heavy chain isoforms. Two of the isoforms (MIIB1 and MIIB2) were recognized by antibodies against the peptide IIB, and the other (MIIA) by the anti-peptide IIA antibodies. Polyclonal anti-platelet myosin antibodies recognized the MIIA isoform, but did not recognize MIIB1 or MIIB2. The isoforms were expressed in a tissue-specific pattern; the MIIB1 isoform was found only in brain.

Amino Acid Sequence↗
PubMed1991

The human hematopoietic progenitor cell antigen (CD34) in vascular neoplasia.

The human hematopoietic progenitor cell antigen CD34 is synthesized and expressed by early normal hematopoietic progenitor cells and by many acute leukemias. Anti-CD34 antibodies also have been reported to stain blood vessels in tissue sections, and, more recently, CD34 mRNA has been detected in vascular endothelial cells. Therefore, the authors studied the diagnostic utility of immunohistochemical CD34 antigen detection in tumors of endothelial cell derivation and compared the results with stains for von Willebrand (vW) factor. A wide variety of epithelial and mesenchymal neoplasms also were examined to assess the specificity of CD34 for vascular neoplasia. Seven cases of angiosarcoma (seven of seven), five cases of Kaposi's sarcoma (five of five), and eight cases of epithelioid hemangioendothelioma (eight of eight) were moderately to strongly positive for CD34. This reactivity was equally intense in frozen sections, alcohol-fixed tissue, and formalin-fixed specimens. In many cases, the malignant endothelial cells stained more strongly than adjacent benign endothelium. Moreover, in most cases CD34 positivity was quantitatively and qualitatively stronger than staining for vW factor. Two cases of hemangiopericytoma (two of two) were CD34 positive but stained less intensely than the angiosarcomas, Kaposi's sarcomas, or hemangioendotheliomas. Five of six cases of hemangioma also stained positively for CD34; the nonreactive tumor in this group was the only one among 28 vascular neoplasms studied that was not reactive for CD34. In comparison, 9 of the 28 vascular tumors did not stain for vW factor. Three hundred fifty-seven tumors of nonvascular derivation also were examined for CD34 antigen expression. Focal light staining was seen in one pulmonary squamous cell carcinoma; moderate to intense staining was observed in half of the epithelioid sarcomas studied (8 of 16) and in a minority of leiomyosarcomas (3 of 22). These findings indicate that CD34 is a sensitive and relatively specific marker for neoplasms of vascular origin.

Antibodies, Monoclonal↗
PubMed1991

Captopril-induced reversal of nitroglycerin tolerance: role of sulfhydryl group vs. ACE-inhibitory activity.

The angiotensin-converting enzyme (ACE) inhibitor captopril has been shown to reverse vascular tolerance to nitroglycerin (NTG). Whether captopril reverses NTG tolerance by providing sulfhydryl (SH) groups or by inhibiting ACE is not clear. To examine this issue, we treated rat aortic rings with buffer, captopril (SH +, ACE inhibitory activity +), enalaprilat (SH-, ACE inhibitory activity +), or N-acetylcysteine (NAC, SH+, ACE inhibitory activity-) prior to their contraction with epinephrine and subsequent relaxation with NTG. Previous exposure of NTG-treated rings resulted in marked resistance to the vasorelaxant effect of a subsequent exposure to NTG in buffer-treated rings. Both NAC and captopril, but not enalaprilat, potentiated the vasorelaxant effects of NTG during the first exposure of vascular rings to NTG and also prevented the development of tolerance to NTG during a second exposure. Buffer-treated rings showed an inability to accumulate cyclic guanosine monophosphate (GMP) in response to a second exposure to NTG. In contrast, both NAC and captopril-pretreated rings demonstrated a persistence of cyclic GMP accumulation during the second NTG exposure. The endothelium-dependent vasodilator acetylcholine (ACh) caused relaxation of the NTG-tolerant rings and also induced cyclic GMP accumulation in these rings. In other experiments, we found that prior exposure of vascular rings to ACh did not cause resistance to the subsequent vasorelaxant effects of ACh. NAC, captopril, and enalaprilat did not modulate the effects of ACh during either the first or subsequent exposures to ACh. In addition, indomethacin did not influence the "protective" effects of NAC or captopril against NTG tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1991

How can we combat excess mortality in Harlem: a one day survey of substance abuse in adult general care.

Our hypothesis was that a one-day survey of all patients hospitalized on Adult General Care would demonstrate a need for expanded addiction services in a municipal teaching hospital in East Harlem. We interviewed 276 patients in Adult General Care on February 16, 1990 to assess whether they abused drugs or alcohol or were hospitalized for reasons related to substance use. Of the 276 patients interviewed, 18 percent used alcohol alone, 14 percent used drugs alone, 17 percent used both drugs and alcohol and 2 percent were hospitalized for reasons related to substance use. One hundred forty or 51 percent of all patients were admitted because of substance use and its sequelae or as a result of violence associated with the buying or selling of drugs. The percentage was highest on one medical floor where 89 percent of the patients were substance users and on medical floors in general where the average was 60 percent. Forty patients or 14 percent were known to be HIV seropositive. Given the high mortality in Harlem, the results of our one-day survey indicate a need for expanded addiction services.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Immunohistochemical assay of neu/c-erbB-2 oncogene product in paraffin-embedded tissues in early breast cancer: retrospective follow-up study of 245 stage I and II cases.

The expression of neu oncoprotein was assayed by immunohistochemistry (IHC) on 245 paraffin-embedded, Stage I and II breast cancers from patients treated at the City of Hope between the years 1980 and 1987. Only cases showing membrane staining were scored as positive. Fifty-four (22%) of the tumors stained positively for neu. Probability of disease-free survival (DFS) and overall survival (OS) was compared based on neu positivity and other prognostic factors. Overall, DFS and OS did not differ significantly among neu-positive and neu-negative cases. However, when only cases with favorable (Stages I and II) nuclear grade were analyzed, OS and DFS were significantly lower in neu-positive cases, with a 9-fold increase in risk of death and a 3-fold increase in risk of relapse. Our findings suggest that immunohistologic study of neu oncoprotein may help to define patients at greater risk among low-stage/low-nuclear-grade patients with breast cancer, a group hitherto recognized as having a good prognosis.

Adult↗
PubMed1991

Immunocytochemical characterization of a monoclonal antibody directed against mitochondria reactive in paraffin-embedded sections.

The monoclonal antibody mES 13 was previously produced against bacterially expressed BALB ras p21 and was reported to have both membrane and cytoplasmic reactivity in formalin-fixed, paraffin-embedded tissue sections. In the current study, the cytoplasmic reactivity of mES 13 is investigated and demonstrated to be mitochondrial. Immunoelectron microscopic studies showed specific labeling of mitochondria without labeling of other organelles. In normal tissues, the antibody strongly labeled tissues known to have large amounts of mitochondria such as renal tubules, hepatocytes, and myocardium. The pattern of reactivity of tumors generally mimicked that of normal tissues, with carcinomas and melanomas usually showing stronger staining than sarcomas and lymphomas. Two granular cell tumors were negative. Among renal neoplasms, mES 13 strongly labeled renal oncocytomas and granular cell renal cell carcinomas and showed weaker staining of clear cell and chromophobe cell tumors. The mES 13 antibody should be useful in the characterization and diagnosis of tumors in which oncocytoma is in the differential diagnosis, especially when only paraffin-embedded tissue is available for study.

Adenoma↗
PubMed1991

Omega-3 polyunsaturated fatty acids augment endothelium-dependent vasorelaxation by enhanced release of EDRF and vasodilator prostaglandins.

Dietary supplementation with fish oil results in augmentation of endothelium-dependent vasorelaxation in experimental animals. The present study was designed to evaluate the direct in vitro effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) on vascular reactivity in isolated rat aortic rings. Aortic rings were incubated with the omega-6PUFA arachidonic acid (AA, 10(-7) M) or the omega-3 PUFAs eicosapentaenoic acid (EPA, 10(-7) M) and docosahexaenoic acid (DHA, 10(-7) M) in an organ bath at 37 degrees C. Following contraction with norepinephrine, changes in isometric force were measured in response to the endothelium-dependent vasodilators acetylcholine (ACh, 10(-10) to 10(-5) M) or the calcium ionophore A23187 (10(-10) to 10(-5) M). Parallel sets of vascular rings were pretreated with the cyclooxygenase inhibitor indomethacin (10(-5) M) or the inhibitor of nitric oxide synthesis NG-monomethyl L-arginine (L-NMMA 5 x 10(-5) M) prior to treatment with AA or EPA. Treatment of rings with EPA resulted in an increase (P less than 0.05) in ACh-mediated vasorelaxation compared both to AA-treated and buffer-treated rings (maximum relaxation 83 +/- 5% vs 46 +/- 5% and 63 +/- 4%, respectively). A similar augmentation was observed in DHA-treated rings. Pretreatment of rings with indomethacin or I-NMMA decreased (P less than 0.05) the ACh-mediated vasorelaxation, although EPA-treated rings showed less (P less than 0.05) attenuation of ACh response compared to AA-treated or untreated control rings.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗