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J Patel

Publications and source records attributed to J Patel.

At least 163 records · Page 9Linked to original sources
PubMed1990

Characterization of the quisqualate receptor linked to phosphoinositide hydrolysis in neurocortical cultures.

Activation of phosphoinositide metabolism is an early event in signal transduction for a number of neurotransmitters and hormones. In primary cultures of rat neurocortical cells, various excitatory amino acids stimulate inositol phosphate production with a rank order of potency of quisqualate greater than ibotenate greater than glutamate greater than kainate, N-methyl-D-aspartate greater than alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionate. This response to excitatory amino acids was insensitive to a variety of excitatory amino acid antagonists including 6-cyano-7-nitroquinoxaline-2,3-dione, 3-3(2-carboxypiperazine-4-yl)propyl-1-phosphonate, and 2-amino-4-phosphonobutyrate. The individual responses of quisqualate-, ibotenate-, and kainate-stimulated inositol phosphate production were not additive. These results suggest that phosphoinositide metabolism activated by excitatory amino acids is mediated by a unique quisqualate-preferring receptor that is not antagonized by known N-methyl-D-aspartate and non-N-methyl-D-aspartate antagonists, and is relatively insensitive to alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionate.

Amino Acids↗
PubMed1990

Role of glycine in the N-methyl-D-aspartate-mediated neuronal cytotoxicity.

Current evidence indicates that glutamate acting via the N-methyl-D-aspartate (NMDA) receptor/ion channel complex plays a major role in the neuronal degeneration associated with a variety of neurological disorders. In this report the role of glycine in NMDA neurotoxicity was examined. We demonstrate that NMDA-mediated neurotoxicity is markedly potentiated by glycine and other amino acids, e.g., D-serine. Putative glycine antagonists HA-966 and 7-chlorokynurenic acid were highly effective in preventing NMDA neurotoxicity, even in the absence of added glycine. The neuroprotective action of HA-966 and 7-chlorokynurenic acid, but not that of NMDA antagonists 3-(2-carboxypiperazine-4-yl)propylphosphonate and MK-801, could be reversed by glycine. These results indicate that glycine, operating through a strychinine-insensitive glycine site, plays a central permissive role in NMDA-mediated neurotoxicity.

Animals↗
PubMed1990

Stereoselectivity for the (R)-enantiomer of HA-966 (1-hydroxy-3-aminopyrrolidone-2) at the glycine site of the N-methyl-D-aspartate receptor complex.

HA-966 (1-hydroxy-3-aminopyrrolidone-2) is an antagonist at the glycine allosteric site of the N-methyl-D-aspartate receptor ionophore complex. Unlike presently known glycine antagonists, HA-966 is chiral. We report stereoselectivity for the (R)-enantiomer at the glycine antagonist site. In [3H]glycine binding, the (R)-enantiomer has an IC50 of 4.1 +/- 0.6 microM. The racemic mixture has an IC50 of 11.2 +/- 0.5 microM, whereas (S)-HA-966 has an IC50 greater than 900 microM. In glycine-stimulated [3H]1-[1-(2- thienyl)cyclohexyl]piperidine binding, the (R)-enantiomer inhibits with an IC50 of 121 +/- 61 microM, whereas the racemic mixture has an IC50 of 216 +/- 113 microM and (S)-HA-966 is inactive. The inhibition by (R)-HA-966 can be prevented by the addition of glycine. (R)-HA-966 and racemic HA-966, but not (S)-HA-966, also prevent N-methyl-D-aspartate cytotoxicity in cortical cultures. The (R)-enantiomer and, less potently, the (S)-enantiomer inhibit N-methyl-D-aspartate-evoked [3H]norepinephrine release from rat hippocampal slices (IC50 values of about 0.3 mM and 1.6 mM, respectively), but only the inhibition by (R)-HA-966 is reversed by added glycine. In glutamate-evoked contractions of the guinea pig ileum, (R)-HA-966 causes a glycine-reversible inhibition (IC50 of about 150 microM), whereas (S)-HA-966 is much less potent (IC50 of greater than 1 mM). These results demonstrate stereoselectivity of the glycine antagonist site of the N-methyl-D-aspartate receptor complex in a variety of tissues and assays. The stereoselectivity also confirms the specificity of N-methyl-D-aspartate receptors in glutamate-evoked contractions of the guinea pig ileum, and supports their similarity to central N-methyl-D-aspartate receptors.

Allosteric Site↗
PubMed1990

6,7-Dinitroquinoxaline-2,3-dione blocks the cytotoxicity of N-methyl-D-aspartate and kainate, but not quisqualate, in cortical cultures.

Based on radioligand binding and electrophysiological studies, quinoxalinediones such as 6,7-dinitroquinoxaline-2,3-dione (DNQX) have been shown to be potent competitive antagonists at the quisqualate and kainate subtypes of the glutamate receptor. In this report we have examined the effects of DNQX on excitatory amino acid neurotoxicity and evoked neurotransmitter release. DNQX was found to be a potent neuroprotective agent against glutamate and N-methyl-D-aspartate (NMDA) neurotoxicity. The data suggest that this neuroprotective activity of DNQX is due to its antagonism of the coagonist activity of glycine at the NMDA receptor-channel complex. The specificity of DNQX for the glycine site associated with the NMDA receptor-channel complex was confirmed in radioligand binding and neurotransmitter release studies. DNQX also prevented kainate neurotoxicity and kainate-evoked neurotransmitter release, presumably by direct competition for the kainate receptor. DNQX, however, did not prevent quisqualate neurotoxicity, suggesting that a novel quisqualate-preferring receptor insensitive to DNQX may mediate quisqualate toxicity.

Animals↗
PubMed1990

Effects of protein kinase C down-regulation on secretory events and proopiomelanocortin gene expression in anterior pituitary tumor (AtT-20) cells.

To elucidate the role of the diacylglycerol-protein kinase C (PKC) pathway in beta-endorphin synthesis and secretion in anterior pituitary corticotrope tumor cells (AtT-20), a procedure for down-regulating PKC activity in the cells was developed. Treatment of AtT-20 cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) led to an increase in [3H]phorbol 12,13-dibutyrate binding to PKC in the membrane fraction of these cells 30 s after its addition to the culture medium. Thereafter, a decrease in both [3H]phorbol 12,13-dibutyrate binding and PKC-specific phosphotransferase activity occurred in a time- and dose-dependent manner in both the cytosolic and membrane fractions. For example, treatment of the cells with 100 nM TPA for 24 h resulted in an almost complete depletion of PKC activity. Immunoreactive beta-endorphin secretion was found to be stimulated two- to fourfold in the control cells after incubation with corticotropin-releasing factor (10(-7) M), forskolin (10(-6) M), or TPA (10(-7) M) for 4 h. In cells rendered PKC deficient, TPA-stimulated immunoreactive beta-endorphin release was abolished, forskolin-stimulated release was unaffected, and corticotropin-releasing factor-stimulated release was depressed. Treatment of control cells with any one of the three stimulatory agents led to an increase in proopiomelanocortin mRNA levels, and these responses were also depressed after TPA pretreatment. The results suggest that physiological processes thought to be entirely cyclic AMP dependent, such as corticotropin-releasing factor-elicited secretion, may be partially dependent on PKC-mediated biochemical events.

Animals↗
PubMed1990

Balloon dilatation of the mitral valve by a single bifoil (2 x 19 mm) or trefoil (3 x 15 mm) catheter.

The efficacy of balloon dilatation of the mitral valve by a bifoil (2 x 19 mm) or trefoil (3 x 15 mm) catheter (single catheter technique) was assessed in 53 patients (mean age 28) with mitral stenosis, most of whom were women. The procedure was unsuccessful in three patients. After balloon dilatation the left atrial pressure decreased from 22 mm Hg to 13 mm Hg and the mitral valve gradient from 12 mm Hg to 4 mm Hg. The mitral valve area increased from 0.7 cm2 to 2.1 cm2. Exercise time on the standard Bruce protocol increased from 3.9 minutes to 7.2 minutes. In 22 (44%) patients mitral regurgitation developed or the grade of regurgitation increased. Left to right shunts with pulmonary to systemic flow ratios greater than 1:5 were detected in four patients. Transient cerebrovascular episodes developed in two patients. One patient died after emergency valve replacement for severe mitral regurgitation. Balloon dilatation of the mitral valve by the single catheter technique with the bifoil or trefoil catheters is an effective treatment for patients with mitral stenosis. Mild mitral regurgitation is a frequent complication of the procedure.

Adolescent↗
PubMed1990

Reevaluation of perioperative myocardial infarction in patients with prior myocardial infarction undergoing noncardiac operations.

We studied 275 patients with prior myocardial infarctions undergoing noncardiac operations to determine the incidence and outcome of perioperative myocardial reinfarction. Perioperative myocardial reinfarction developed in 13 patients (4.7%) of whom 3 (23%) died of cardiac causes. When time between prior myocardial infarction and the date of anesthesia was analyzed, the incidence of perioperative myocardial reinfarction was 4.3% at 0-3 mo, 0 at 4-6 mo, 5.7% at greater than 6 mo, and 3.3% at an indeterminate exact interval. None of the variables analyzed showed any significant correlation with the rate of reinfarction. The urgency of operation and aortic or vascular procedures were the only variables that approached, but failed to achieve, statistical significance.

Adult↗
PubMed1990

A rural outbreak of Legionnaires' disease linked to visiting a retail store.

Between May 7 and June 7, 1986, 27 residents of a rural county in Maryland developed legionellosis, and two died. Legionella pneumophila serogroup 1 was cultured from the sputum of two patients and identified in lung tissue of a third patient by direct fluorescent antibody staining. An additional 11 patients had four-fold rises in antibody titer to L. pneumophila, and 13 had single titers greater than or equal to 1:256. To determine risk factors for disease, we performed a case-control study. Twelve of 16 case-patients reported visiting store A in the two weeks before onset of illness compared with four of 28 control-patients. A serologic survey of employees showed that employees of store A were 3.63 times more likely than control employees to have titers of antibody to L. pneumophila greater than or equal to 1:256 (95% confidence intervals 0.8, 16.7). Cultures of soil specimens, samples of water from the hot water system of store A and from stagnant ponds near store A collected five weeks after the end of the outbreak were negative for Legionella species. Store A was adjacent to a site of excavation and construction during May 1986, when the community was experiencing an extended drought. This investigation suggests that exposure to excavation and construction activity may be a risk factor for legionellosis.

Adult↗
PubMed1990

Treatment options and recurrence potential for cystosarcoma phyllodes.

The surgical treatment and outcome of 31 women with a pathologic diagnosis of cystosarcoma phyllodes at Roswell Park Memorial Institute were reviewed. Surgical excision was performed upon 20 patients with a mean tumor size of 4.5 centimeters (range of 1.0 to 9.0 centimeters). Mastectomy was performed initially upon 11 patients with a mean tumor size of 15 centimeters (range of 3 to 40 centimeters). Local recurrence was seen in five patients treated by excision and one patient treated by mastectomy. All patients retreated by repeat excisions were controlled; one patient retreated with mastectomy died with local recurrence and distant disease. Routine axillary dissections were not performed. Involvement of the axillary lymph nodes occurred in one patient and was associated with advanced systemic disease. Local recurrences did not imply associated systemic spread and were controlled in five of six patients by repeat excision or mastectomy. Although the benign behavior of this tumor is commonly emphasized, four of the patients we studied died of malignant spread of cystosarcoma phyllodes.

Adolescent↗
PubMed1990

Glycine-evoked neurotransmitter release from rat hippocampal brain slices: evidence for the involvement of glutaminergic transmission.

Glycine caused a concentration-dependent evoked release of [3H]norepinephrine from rat hippocampal brain slices. Other amino acids evoked [3H]norepinephrine release with a rank order of potency: L-serine greater than or equal to glycine greater than beta-alanine greater than D-serine. Strychnine inhibited [3H]norepinephrine release evoked by both glycine and L-serine, but was less effective in inhibiting the release evoked by N-methyl-D-aspartate (NMDA) and kainic acid. Inhibitors of the NMDA receptor/ionophore complex, MK-801, CPP and Mg++, as well as the strychnine-insensitive glycine receptor antagonist, HA-966, caused an incomplete inhibition (maximum approximately 60%) of glycine-evoked [3H]norepinephrine release. The potencies with which MK-801, CPP and Mg++ inhibited glycine- and NMDA-evoked [3H]norepinephrine release were very similar. The combination of MK-801 plus kynurenic acid, a nonselective glutamate receptor antagonist, caused no greater inhibition of glycine-evoked release than MK-801, alone. omega-Conotoxin GVIA, an inhibitor of neuronal L- and N-type voltage-sensitive calcium channels, inhibited glycine-evoked [3H]norepinephrine release by approximately 50%, whereas the L-channel inhibitor PN 200-110 had no significant effect. The combination of MK-801 plus omega-conotoxin GVIA caused only a slightly greater inhibition (P greater than .05) of glycine-evoked release than MK-801 alone. Tetrodotoxin inhibited glycine-evoked release of [3H]norepinephrine by approximately 75%. The inhibitory effects of tetrodotoxin and omega-conotoxin GVIA suggest that voltage-sensitive sodium channels and N-type voltage-sensitive calcium channels are important mediators of glycine-evoked release of [3H]norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1990

CA 125 levels in menopausal women.

To assess the use of CA 125 as a potential screening test for ovarian cancer, it is necessary to understand how the test performs among cancer-free women, who would constitute the overwhelming majority of those being tested at any time. Two hundred fifty-eight menopausal volunteers who were not seeking gynecologic care had CA 125 measured on two occasions and also underwent transvaginal ultrasonography to measure ovarian volumes. Only one subject had a CA 125 level greater than 35 U/mL. The mean value for CA 125 was 5.6 +/- 3.5 U/mL. Within women, the correlation between two tests was very high (r = 0.82). Among women with apparently normal ovaries, CA 125 values were low, tightly distributed, and reproducible; these findings indicate that the test may prove to be useful and cost-effective in a screening program. The correlation between CA 125 values and ovarian volume determined by sonogram was low (r = 0.11). The independence of these two tests would also be desirable in any screening program. Other studies have found normal women to have higher levels of CA 125 with wider distributions than found here; further evaluation of test performance at these low levels is needed.

Adult↗
PubMed1989

HA-966 acts at a modulatory glycine site to inhibit N-methyl-D-aspartate-evoked neurotransmitter release.

The role of endogenous glycine in supporting N-methyl-D-aspartate (NMDA)-evoked neurotransmitter release was investigated. HA-966 (1-hydroxy-3-aminopyrrolidone-2) inhibited NMDA-evoked release of [3H]norepinephrine from rat hippocampal brain slices, but was much less effective in inhibiting [3H]norepinephrine release evoked by kainic acid (KA). Glycine (1 mM) reversed the HA-966 (1 mM) antagonism of NMDA-evoked release of [3H]norepinephrine. Strychnine (10 microM) had no effect on the ability of glycine to reverse HA-966 antagonism of NMDA-evoked neurotransmitter release. Other amino acids were also capable of reversing the HA-966 antagonism of NMDA-evoked [3H]norepinephrine release with a rank order of potency: D-serine greater than or equal to glycine much greater than L-serine approximately beta-alanine. These same compounds inhibited strychnine-insensitive [3H]glycine binding to rat cortical membrane fragments with a rank order of potency: glycine greater than D-serine much greater than L-serine greater than or equal to beta-alanine. In addition, HA-966 inhibited [3H]glycine binding (IC50 = 8.5 microM). The results suggest that HA-966 antagonism of NMDA-evoked neurotransmitter release is due to the inhibition of endogenous glycine acting at a strychnine-insensitive modulatory glycine site associated with the NMDA receptor/ionophore complex.

Animals↗
PubMed1989

Protective effect of the anterior lens capsule during extracapsular cataract extraction. Part II. Preliminary results of clinical study.

In a clinical study, 61 patients underwent phacoemulsification with subsequent intraocular lens (IOL) implantation. An intercapsular capsulotomy with phacoemulsification was performed on 23 patients and a can opener capsulotomy with phacoemulsification on 38 patients. Wide-field specular microscopy was performed preoperatively and postoperatively on all of the eyes in the study. The cell counts were not divulged to the surgeon before or at the time of surgery. Average endothelial cell loss for the intercapsular technique was 3.9%; with the can opener technique, the average cell loss was 10.1%. This difference was statistically significant (P less than 0.01). Positive correlations between endothelial cell loss relating to ultrasound time and/or the hardness of the cataract existed for the can opener group only (P less than 0.01). These results demonstrate that a protective effect is provided by the presence of the anterior lens capsule during lens substance removal.

Aged↗
PubMed1989

Myoglobin: an evaluation of its role as a marker of rhabdomyosarcomas.

Tumour markers now have an established role in tumour diagnosis and patient management. However, antibodies used to detect these tumour markers have in some instances proved unreliable, with a low rate of sensitivity and specificity. In this study we wished to evaluate the role of a commercial antibody to myoglobin as a marker of rhabdomyosarcomas. The purpose of this investigation was to assess the sensitivity and specificity of myoglobin antiserum as a marker of rhabdomyosarcomas. This was performed by reacting a large number of tumours (sarcomas, carcinomas and melanomas) with a polyclonal anti human myoglobin antiserum. Staining was demonstrated in 60% of rhabdomyosarcomas. Only two tumours from a total of 226 non-skeletal muscle tumours showed a positive reaction (0.88%). One was a leiomyosarcoma and the other had been classified as an undifferentiated sarcoma but a rhabdomyosarcoma was included in its differential diagnosis. It is of interest that both had been earlier irradiated. This antiserum was therefore a specific but not a very sensitive tumor marker. Its rate of staining of rhabdomyosarcomas is compared with the results in the literature. A great disparity is found and the reasons for this are discussed.

Adolescent↗
PubMed1989

Differential expression of an 80-kDa protein kinase C substrate in preneoplastic and neoplastic mouse JB6 cells.

An 80-kDa protein (p80), previously reported to be a major protein kinase C substrate in preneoplastic JB6 mouse epidermal cells, has been shown to be transiently phosphorylated by phorbol 12-O-tetradecanoate 13-acetate. Phosphorylation was maximal at 2 hr of phorbol 12-O-tetradecanoate 13-acetate treatment and returned to basal levels by 24 hr. In contrast, using a p80-specific antibody, we found that phorbol 12-O-tetradecanoate 13-acetate treatment produced no increase in p80 concentration. p80 showed a progressive decrease in JB6 cells during progression from a preneoplastic to neoplastic phenotype. The lack of p80 expression in neoplastic cells was not attributable to lack of protein kinase C; the protein kinase activity and protein concentration were similar in cells of all three phenotypes. When p80 mRNA was analyzed by hybridization to a putative p80 cDNA clone, its relative concentration paralleled that of p80 protein, with high levels present in preneoplastic JB6 cells, and little or no evidence for p80-hybridizing RNA in transformed cells. Thus, p80 appears to be regulated pretranslationally at the level of mRNA concentration during preneoplastic progression in mouse epidermal JB6 cells.

Animals↗
PubMed1989

Prevalence of risk behaviors and HIV infection in Maryland STD clinics.

Persons who are receiving evaluation and treatment for sexually transmitted diseases are at moderately increased risk for acquiring HIV infections. The scope of STD clinic services should be broadened to include counseling, education, and referral services for health needs related to risk of HIV infection.

Adolescent↗