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Biomedical subjects

J Patel

Publications and source records attributed to J Patel.

At least 127 records · Page 7Linked to original sources
PubMed1993

Effect of modulation of polymorphonuclear leukocyte migration with anti-CD18 antibody on pathogenesis of experimental otitis media in guinea pigs.

Guinea pigs were treated with anti-CD18 antibody (M8), and subsequently middle ears (ME) were infected with nontypeable Haemophilus influenzae. Forty-eight hours after infection, the ME washes of these animals had significantly lower polymorphonuclear leukocyte numbers but higher bacterial counts compared with washes of animals treated with control antibody (M11) or saline. The edema and epithelial damage of ME tissues correlated directly with polymorphonuclear leukocyte numbers and not bacterial counts.

Animals↗
PubMed1993

Cervical ribs: a cause of distal and cerebral embolism.

The thoracic outlet syndrome occurs when the neurovascular structures are compressed as they traverse the thoracic outlet. Degenerative changes can occur in the subclavian artery and the vessel may become a source of embolism with the risk of acute or chronic upper limb ischaemia. Rarely, distal thromboembolism in the thoracic outlet syndrome may be associated with retrograde flow when there is the added risk of cerebral thromboembolism.

Adult↗
PubMed1993

Radiosurgery for acoustic neuroma.

Radiosurgery has been used for many years with great success for the treatment of acoustic neuroma. We present three cases in Louisiana using the E L Fisher system, the results of treatment, and a discussion of acoustic neuroma.

Aged↗
PubMed1992

Serum platelet-reactive IgG of autoimmune thrombocytopenic purpura patients is not F(ab')2 mediated and a function of storage.

Serum platelet-reactive and glycoprotein (GP) IIb-GPIIIa-reactive IgG and F(ab')2 was examined in 39 patients with classic autoimmune thrombocytopenic purpura (ATP), two patients with anti-PLA1 antibody and 25 control subjects in an enzyme-linked immunosorbent assay. IgG was purified by diethyl aminoethyl chromatography and centrifuged at 100,000g before testing of the supernatant. Significant IgG binding (threefold to fourfold control IgG binding) was noted with 8 of 17 ATP patients' IgG, 2 anti-PLA1 IgGs, and 2 ATP patients with multiple platelet transfusions. However, F(ab')2 fragments of nine of nine positive ATP IgGs were nonreactive; F(ab')2 from the two anti-PLA1 and two multiply transfused ATP IgGs were as reactive as their intact IgG. Antiplatelet or anti-GPIIb-GPIIIa reactivity of ATP IgG could be adsorbed to fixed platelets or solid-phase GPIIb-GPIIIa and eluted with 0.1 mol/L glycine, pH 2.5. However, binding of IgG to GPIIb-GPIIIa could not be inhibited with F(ab')2 of ATP IgG or Fc fragments of control subjects. When platelet- or GPIIb-GPIIIa-reactive ATP IgG was applied to a Sephacryl 300 gel filtration column, no reactivity was noted in the 7S region, whereas anti-PLA1 localized to this region. Antiplatelet or anti-GPIIb-GPIIIa reactivity was noted in the void volume and accompanied by a high molecular weight protein region. An immunoblot of the void volume fraction with goat antihuman IgG (gamma chain) antibody showed high molecular weight bands greater than 250 Kd, which after reduction converted to a 55-Kd heavy-chain band. Fresh samples of ATP and control IgG processed within 1 to 2 days of blood withdrawal had no reactivity for GPIIb-GPIIIa. After storage at -20 degrees C for greater than 3 months, 5 of 19 ATP IgG became reactive, whereas 16 of 16 controls were nonreactive. Thus, platelet-reactive IgG of ATP sera appears to be caused by the development of IgG aggregates held together by disulfide bonds that develop on storage, and is not F(ab')2 mediated.

Binding Sites, Antibody↗
PubMed1992

5,10-Methylenetetrahydro-5-deazafolic acid and analogues: synthesis and biological activities.

The synthesis of 5,10-methylene-5-deazatetrahydrofolic acid (2), a stable, rigid analogue of 5,10-methylenetetrahydrofolate (1), is reported as a potential inhibitor of thymidylate synthase. The target compound was obtained by a Fisher-indole type cyclization of the hydrazone 16 from 2-amino-6-hydrazino-4-oxopyrimidine (10) and diethyl N-[4-(3-formyl-1-pyrrolyl)benzoyl]-L-glutamate (15) followed by catalytic reduction of the product 17. Similarly, modification of the Fisher-indole type cyclization of the appropriate hydrazone precursors 11 and 12 afforded the nonclassical analogues 3-amino-7,8,9-trimethyl-2H-pyrrolo[3',4':4,5]pyrido[2,3-d]pyrimidin-1- one (4) and 3-amino-8-benzyl-7,9-dimethyl-2H-pyrrolo[3',4':4,5]pyrido [2,3-d]pyrimidin-1-one (5), respectively. The target compound 2, its aromatic precursor 18, and the nonclassical analogue 4 were evaluated as inhibitors of the growth of Manca human lymphoma cells and also as inhibitors of human dihydrofolate reductase, human thymidylate synthase, glycinamide ribonucleotide formyltransferase, and aminoimidazole carboxamide ribonucleotide formyltransferase. Compound 18 showed weak inhibition of lymphoma cell growth (IC50 = 42 microM) and of AICAR formylTF (IC50 = 17 microM). Compounds 2 and 4 did not inhibit lymphoma cell growth or thymidylate synthase. The inactivity of 2 was attributed to its lack of flexibility leading to its inability to bind to thymidylate synthase.

Antineoplastic Agents↗
PubMed1992

Quisqualate neurotoxicity in rat cortical cultures: pharmacology and mechanisms.

Quisqualate is a potent neurotoxin in cortical cultures of the rat. Unlike N-methyl-D-aspartate (NMDA), the toxicity of quisqualate is due to overstimulation of a membrane receptor after the agonist has been removed. This receptor appears to be the 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor since 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX) are potent antagonists when added to the post incubation media. NBQX and DNQX are ineffective when present only during quisqualate exposure, indicating the AMPA receptor is not involved in the initial event. Transfer of culture media 30 min after quisqualate exposure to either neuronal or non-neuronal cells was found to cause toxicity in previously untreated neuronal cells. This effect could not be reproduced with NMDA. The neurotoxic chain of events could be interrupted during quisqualate exposure by removal of sodium from the incubation media, suggesting the involvement of a sodium-dependent plasma membrane uptake mechanism. Quisqualate may be continually recycled by internalization and release, causing neurotoxicity by persistent stimulation of the AMPA receptor.

Animals↗
PubMed1992

High-level expression of the cloned genes encoding the subunits of and intact DNA methyltransferase, M.EcoR124.

We have cloned the genes coding for the two subunits (HsdM and HsdS) of the type-I DNA methyltransferase (MTase), M.EcoR124, into the specially constructed expression vector, pJ119. These subunits have been synthesized together as an intact MTase. We have also cloned the individual subunit-encoding genes under the control of the T7 gene 10 promoter or the lacUV5 promoter. High levels of expression have been obtained in all cases. While HsdM was found to be soluble, HsdS was insoluble. However, in the presence of the co-produced HsdM subunit, HsdS was found in the soluble fraction as part of an active MTase. We have partially purified the cloned multi-subunit enzyme and shown that it is capable of DNA methylation both in vivo and in vitro.

Amino Acid Sequence↗
PubMed1992

Purification and biochemical characterisation of the EcoR124 type I modification methylase.

Large scale purification of the type I modification methylase EcoR124 has been achieved from an over-expressing strain by a two step procedure using ion-exchange and heparin chromatography. Pure methylase is obtained at a yield of 30 mg per gm of cell paste. Measurements of the molecular weight and subunit stoichiometry show that the enzyme is a trimeric complex of 162 kDa consisting of two subunits of HsdM (58 kDa) and one subunit of HsdS (46 kDa). The purified enzyme can methylate a DNA fragment bearing its cognate recognition sequence. Binding of the methylase to synthetic DNA fragments containing either the EcoR124 recognition sequence GAAN6RTCG, or the recognition sequence GAAN7RTCG of the related enzyme EcoR124/3, was followed by fluorescence competition assays and by gel retardation analysis. The results show that the methylase binds to its correct sequence with an affinity of the order 10(8) M-1 forming a 1:1 complex with the DNA. The affinity for the incorrect sequence, differing by an additional base pair in the non-specific spacer, is almost two orders of magnitude lower.

Anilino Naphthalenesulfonates↗
PubMed1992

Chronic lithium administration alters a prominent PKC substrate in rat hippocampus.

The therapeutic effect of lithium in the treatment of bipolar disorder exhibits a significant delay in the onset of action and a persistence of efficacy beyond abrupt discontinuation of treatment. Lithium is known to alter receptor-coupled phosphoinositide second messenger pathway in brain, resulting in indirect changes in an endogenous activator of protein kinase C (PKC). Such evidence has suggested that PKC may be involved in the mechanism of action of lithium in the brain. PKC represents a site wherein long-term regulatory changes in cell function occur through the phosphorylation of specific phosphoproteins involved in processes including neurotransmitter release and receptor activation. In studies of rats exposed to lithium, however, we have found no significant effects of chronic administration on the relative activity, subcellular distribution, or activation of PKC in hippocampus. We did find a major reduction in the in vitro PKC mediated phosphorylation of two major substrates, 83 kDa and 45 kDa, in hippocampus of rats exposed to chronic lithium and maintaining clinically relevant therapeutic levels in brain. Using immunoblot analysis we have identified a known myristoylated alanine-rich C kinase substrate (MARCKS) at 83 kDa. In vivo levels of MARCKS in hippocampus were found to be significantly reduced after chronic lithium exposure. These findings persist in animals withdrawn from lithium, but are not apparent following acute treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Regional differences in evoked dopamine efflux in brain slices of rat anterior and posterior caudate putamen.

Fast cyclic voltammetry using carbon fibre microelectrodes in rat brain slices, was used to investigate regional differences in electrically-evoked dopamine (DA) efflux at 10 different sites in the anterior caudate putamen (aCPu) and 10 sites in the posterior caudate putamen (pCPu). For each site DA overflow was evoked by both single pulse (1P) stimulation and by trains of 25 pulses applied at a frequency of 50 Hz (25P/50 Hz). Peak DA efflux evoked by 1P was about 58% greater in the aCPu (0.19 mumol/l DA) than in the pCPu (0.12 mumol/l DA), but showed no mediolateral variation in either region. Peak DA efflux evoked by 25P/50 Hz relative to 1P efflux also varied between the two regions; the aCPu contained predominantly low ratio (25P/50 Hz: 1P) sites ranging from 1.47 to 3.71, whereas in the pCPu these ratios were higher, ranging from 2.73 to 9.40, and were particularly high in the dorsomedial region of the pCPu. Efflux detected in low ratio sites of the aCPu showed little dependence on the frequency (10 to 500 Hz), or the number of pulses (5 to 20) in a train. By contrast DA efflux evoked in high ratio sites of the pCPu responded in a pulse and frequency dependent manner, the maximum ratio (approximately 8 times 1P) being at 20P/20 Hz. Interestingly the frequency response relationship obtained in the pCPu resembled the profile observed in the nucleus accumbens (NAc). Voltammetric evidence and experiments with selective reuptake blockers indicated that only DA was measured in our studies and 5-HT did not significantly contribute to the frequency dependent pattern of efflux detected in high ratio sites of the pCPu, where striatal 5-HT concentrations are highest. Experiments with the selective D2 receptor antagonists metoclopramide or (-)sulpiride revealed that under our experimental conditions, DA efflux in the aCPu was not modulated by DA autoreceptor activation. By contrast, autoreceptor modulation did occur in high ratio sites of the pCPu at stimulations lasting longer than approximately 1000 ms. These observations support the concept that the caudate putamen is heterogeneously organised with respect to the frequency characteristics of evoked DA release. The factors controlling frequency dependent release under these conditions may be a function of A10 innervation, since high ratio release sites occur in areas where the density of such innervation is greatest, for example, the dorsomedial pCPu. This is supported by the observation that high ratio release sites are also found in the NAc, which receives dopaminergic fibres predominantly from an A10 region.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Effect of respiratory syncytial virus on adherence, colonization and immunity of non-typable Haemophilus influenzae: implications for otitis media.

Adherence of non-typable Haemophilus influenzae to respiratory epithelium was evaluated in a cotton rat model of respiratory syncytial virus (RSV) infection. Colonization with non-typable H. influenzae increased to a maximum within 4 days of RSV infection compared to RSV negative controls (4.58 +/- 0.17 vs 3.82 +/- 0.23 log colony forming units (CFU) per ml, P less than 0.05) and then declined over the subsequent 10 days (2.0 +/- 0 vs 3.78 +/- 0.39 CFU per ml, P less than 0.0001). In a second series of experiments, attachment of non-typable H. influenzae to epithelial cells collected from RSV infected cotton rats at the time of maximum virus replication was not different from controls (57.4 +/- 18.3 vs 52.0 +/- 24.3 bacteria per 50 cells). Systemic immunity to non-typable H. influenzae as measured by IgG-specific antibody to the outer membrane complex and bactericidal antibody did not influence colonization. These data suggest that colonization with non-typable H. influenzae is significantly affected by a concurrent infection with RSV; however, the site of bacterial attachment is not known.

Animals↗
PubMed1992

Nursing home outbreak of influenza A (H3N2): evaluation of vaccine efficacy and influenza case definitions.

OBJECTIVES: Describe an outbreak of influenza A (H3N2); provide an analysis of vaccine efficacy; measure the sensitivity, specificity, and positive predictive value of 3 clinical case definitions of influenza. SETTING: A nursing home in Washington County, Maryland. The outbreak involved 52 residents (attack rate = 47.7%) and at least 10 of 140 employees (minimum attack rate = 7.1%). RESULTS: Twenty-five residents exhibited a 4-fold or greater increase in titer to influenza A/Sichuan/2/87. Vaccine efficacy was measured at -7.1%, suggesting that the influenza vaccine in 1988/1989 did not offer optimal protection against influenza A infection for the institutionalized elderly. CONCLUSIONS: The outbreak was a clear indicator of the need for rapid diagnosis. With the use of rapid diagnostic tests, influenza A could have been detected in time to use amantadine.

Aged↗
PubMed1992

Prophylactic miconazole oral gel for the prevention of neonatal fungal rectal colonization and systemic infection.

Prior rectal colonization with fungi may be an important risk factor for development of systemic fungal infection in the neonate. This placebo-controlled study evaluated the benefits of miconazole oral gel in the prevention of fungal rectal colonization and systemic infection in high risk neonates admitted to the Neonatal Intensive Care Unit. Repeated oral application of miconazole gel reduced the overall prevalence of postnatally acquired rectal colonization; a yeast was grown in 19.5% of the weekly rectal swabs in the miconazole-treated group compared with 36.2% in the control group (69 of 354 vs. 146 of 403, P < 0.0001). There was no reduction in the incidence of systemic fungal infection in the two groups although the overall incidence of the infection was low in both groups, at 2.0% vs. 2.6% (6 of 298 vs. 8 of 302, P not significant). No relationship was shown between prior rectal colonization and subsequent systemic fungal infections in either of the two groups. This study does not support the use of prophylactic miconazole oral gel for the prevention of neonatal systemic fungal infections.

Administration, Oral↗
PubMed1992

Predictive value of Doppler ultrasonography in renal transplantation.

During a 17-month period, 268 Doppler sonography studies were performed on 46 consecutive renal transplant patients. There were 35 episodes of acute rejection in 10 patients, 8 episodes of delayed function and 47 episodes of high cyclosporine levels (greater than 800 ng/dl by TDX method) in 21 patients. Defining an abnormal resistive index (RI) as greater than 0.8 or a 20% increase above baseline, the test has a specificity of 99% and a sensitivity of 94% in the 1st month post-transplant and had an overall predictive value of 99%. Episodes of high cyclosporine levels ranging from 800 to 1650 ng/dl did not correlate with a high RI except in one circumstance with concurrent acute rejection. Within the 1st month post-transplant, only 1 false-negative study occurred. An additional 8 false-negative studies occurred beyond 1 month post-transplant. Patients with delayed function are separated into three groups based on the Doppler ultrasounds: Group I, patients with an accelerated acute rejection with high RI (N = 2); Group II, patients with true ischemic acute tubular necrosis with normal RI (N = 2); and Group III, patients with possible immunologically-mediated delayed function with intermediate RI between 0.6 and 0.8 (N = 4). Doppler ultrasound is a useful ancillary test to confirm the clinical suspicion of acute rejection. Since high cyclosporine levels do not cause an increase in RI, Doppler ultrasound may help to avoid confusion between acute rejection and cyclosporine toxicity. Additionally, this test may offer insight into the cause of early post-transplant renal dysfunction.

Cyclosporine↗
PubMed1992

AIDS--the Baragwanath experience. Part I. Epidemiology of HIV infection at Baragwanath Hospital, 1988-1990.

This four-part series describes the experience with HIV infection at Baragwanath Hospital to December 1990. In this first part we give an overview of the emergence of this disease and of its impact on the hospital. From July 1988 to December 1990, 426 HIV-positive individuals were identified: 58 were women identified in surveys at antenatal and gynaecology clinics, 60 were parents of infected babies or sexual contacts of hospitalised patients, and 30 were not inpatients (mainly patients at Soweto clinics). Of the 278 inpatients, 16 were identified in the latter 6 months of 1988, 54 in 1989 and 208 in 1990. Fifty-one per cent of the patients were in the adult medical wards, 11% in surgery, 20% in paediatrics and 18% in other disciplines. One per cent of sera from Wassermann reaction-positive women in mid-1990 were HIV-positive; this also applied to 1% of antenatal women in late 1990 and 2.7% of women with pelvic inflammatory disease. The HIV antigen assay is a useful adjunctive assay in the evaluation of HIV-antibody-positive children. The false/true-positive ratio of a rapid HIV antibody test was 2:1 initially, but the specificity improved with experience. The use of rapid diagnostic assays for HIV must be restricted to laboratories with experience in reading assays and where definitive follow-up testing is assured.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Microcirculatory disturbances following the passage of emboli in an experimental free-flap model.

Following completion of arterial repair in an experimental free-flap model, platelet emboli have been observed passing through the microcirculation downstream. The purpose of this experimental study was to observe and quantitate changes in capillary perfusion occurring subsequent to these events. The isolated rat cremaster model was used. For 6 hours subsequent to surgical injury of the main artery in this model, the number of emboli and the number of perfused capillaries downstream were counted. In eight rats having an intentional arterial wall injury, emboli were consistently seen during the first hour of reflow. In the nine control animals having no arterial injury, no emboli were seen. The presence of emboli in the cremaster muscle, resulting from the arterial injury, was associated with a significant reduction in the number of perfused capillaries. We suggest that the observed decrease in capillary perfusion was associated with microemboli that produced an adverse effect for several hours after their initial presence in the circulation.

Analysis of Variance↗