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T Patel

Publications and source records attributed to T Patel.

At least 55 records · Page 3Linked to original sources
PubMed1997

Risperidone-induced neuroleptic malignant syndrome.

Risperidone is an antipsychotic drug used for the treatment of schizophrenia. It was expected that this atypical neuroleptic agent would not cause dystonia or neuroleptic malignant syndrome (NMS) owing to its unique mechanism of action with attenuated anti-dopaminergic activity and more potent antiserotoninergic activity. We report the case of a geriatric patient in whom signs and symptoms consistent with NMS developed after 3 weeks of risperidone therapy. The patient presented with fever, mental status changes, tremor, and rigidity. His laboratory findings were significant for increased serum creatine phosphokinase, hypernatremia, and metabolic acidosis. There have been few reported cases of risperidone-induced NMS. Health care providers should be aware of the risk of risperidone-induced NMS.

Aged↗
PubMed1996

The role of proteases during apoptosis.

The importance of proteases during apoptosis is becoming increasingly apparent. Because apoptosis contributes to a diverse variety of disease processes, understanding the roles played by proteases and their inhibitors might provide insight into the pathogenesis of these conditions and suggest novel therapeutic strategies. In this review, we discuss the involvement and role of specific proteases, substrates, and protease inhibitors that appear to participate in the apoptotic process.

Animals↗
PubMed1996

Prolactin (PRL) is a zinc-binding protein. I. Zinc interactions with monomeric PRL and divalent cation protection of intragranular PRL cysteine thiols.

PRL in secretory granules is osmotically inert. Previous studies by us and others have suggested that this is due in part to hormone oligomerization. Data suggest intermolecular disulfide bridges and/or intermolecular ionic interactions, as thiols, urea, and chelators increase monomerization of the majority of granule PRL. Because of the inhibitory effect of zinc on PRL release from isolated granules and the effects of zinc on the specific packing of PRL within granules, we examined the possibility that zinc contributed to the stability and/or oligomerization of intragranular PRL. To do this, we first analyzed zinc binding to purified monomeric rat PRL in solution. Zinc binding was demonstrated using the chromogenic chelator 5,5'-nitrilodibarbituric acid (murexide) and was confirmed by matrix-assisted, time of flight mass analysis. Because these spectrophotometric methods were not applicable for intragranular PRL studies, we tested the influence of zinc on granule PRL indirectly. As hormone free thiols were potentially formed during PRL oligomerization and storage, these were possible sites for hormone-divalent cation interactions. By derivatization of thiols with 4-vinyl pyridine and isolation of the carboxyterminal region of granule PRL, we found that a proportion of the cysteines 189 and 197 occurred as thiols and not disulfides. These thiols were only detectable when EDTA was present in the granule incubations. It is proposed that binding of zinc stabilizes the intermolecularly bonded storage form of PRL, in part by protection of hormone free thiols. Removal of the divalent cation and exposure of free thiols could be what initiates the thiol-disulfide interchange necessary for conversion of intermolecular to intramolecular disulfide bonds before exocytosis. Experimentally, both urea and EDTA could remove zinc, thus initiating monomerization and explaining how these agents as well as thiols achieve monomerization.

Amino Acid Sequence↗
PubMed1995

A fluorometric assay for quantitating DNA strand breaks during apoptosis.

Few techniques exist for quantitating DNA fragmentation during apoptosis. Our aim was to develop a quantitative assay for DNA fragmentation in apoptosis by enzymatically labeling DNA with a fluorescent dideoxynucleotide. Terminal deoxynucleotidyl transferase was used to enzymatically label 3'-OH DNA ends with fluorescein-12-dideoxyuridine triphosphate in an assay referred to as fluorophore end-labeling. Because only one labeled dideoxynucleotide can be added per 3'-OH end of DNA, the fluorescence intensity is directly proportional to the number of DNA strand breaks. The sensitivity and validation of this approach were first established in isolated calf thymus DNA treated with the endonuclease, DNase I; and excellent correlation was observed between fluorophore end-labeling and an isotopic approach to quantitate 3'-OH ends of DNA. Quantitation of DNA strand breaks was then obtained in nuclei isolated from hepatocytes undergoing apoptosis using fluorescent digitized microscopy, flow cytometry, and fluorometry. In addition to its quantitative aspects, fluorophore end-labeling proved to be quite sensitive as it detected DNA strand breaks prior to the morphologic changes of apoptosis or the development of the hypodiploid state as assessed by fluorescence microscopy and flow cytometry, respectively. This assay should prove useful for studying the molecular mechanisms leading to DNA cleavage during apoptosis.

Animals↗
PubMed1995

Apoptosis and hepatobiliary disease.

In this review we have attempted to summarize recent information on the role of apoptosis in normal liver biology and as a pathophysiological mechanism of cell death during hepatobiliary disease. Apoptosis is an important mechanism of cell injury and death in pathogenic settings as diverse as cell-mediated cytotoxicity, drug and chemical toxicity, carcinogenesis, viral disease, and autoimmune disease. Several factors account for the widespread attention and flurry of investigative activity into the phenomenon of apoptosis including the following: (1) realization that apoptosis is an important component of the behavior of all cells; (2) increasing evidence supporting a role for apoptotic cell death in diverse pathological settings; (3) elucidation of the biochemical pathways and insight into the genetic and molecular regulation of the process; and (4) development of new techniques to identify cells undergoing apoptosis. Recognition of the importance and role of apoptosis in hepatobiliary disease should stimulate interest and promote basic research toward understanding the mechanisms involved. Subsequent investigation into defining the cellular regulatory mechanisms and biochemical processes involved will be fertile ground for future research that may ultimately lead to novel therapeutic approaches for autoimmune diseases, malignancies, and viral disease.

Animals↗
PubMed1995

The effect of head and neck irradiation on taste dysfunction: a prospective study.

Taste loss is a major cause of morbidity in patients undergoing head and neck irradiation. In a prospective study, 26 patients undergoing radical head and neck irradiation at the Royal Marsden Hospital, Sutton, and the Queen Elizabeth Hospital, Birmingham, were assessed for taste loss and xerostomia. Taste was tested using a subjective questionnaire and by objective taste testing with a series of solute solutions (sucrose, sodium chloride, urea and hydrochloric acid) at increasing concentrations, to determine the threshold level of taste sensation, both before and after radiotherapy. Xerostomia was assessed using a patient questionnaire. The volume of tongue and parotid contained within the high dose volume of the radiation treatment field was determined for each patient and correlated with the degree of objective and subjective taste loss as well as the degree of xerostomia. The results have shown that both objective (r = 0.59; P = 0.0016) and subjective taste loss (r = 0.78; P = 0.0001) was significantly associated with the proportion of tongue, but not parotid, contained within the radiation treatment field. The data gave no evidence to suggest any relationship between recovery of taste loss and volume of parotid or tongue irradiated. However, recovery of subjective taste loss, 1 month after completing radiotherapy was seen in two patients, both of whom had been treated using a wedge pair technique to avoid the contralateral area of the tongue. Changes in xerostomia were significantly correlated with the proportions of both tongue (r = 0.54; P = 0.004) and parotid (r = 0.82; P = 0.0001) within the radiation treatment fields.(ABSTRACT TRUNCATED AT 250 WORDS)

Head and Neck Neoplasms↗
PubMed1995

Nuclear serine protease activity contributes to bile acid-induced apoptosis in hepatocytes.

Glycodeoxycholate (GDC) induces apoptosis in hepatocytes by a mechanism associated with DNA cleavage by endonucleases. In many models of apoptosis, proteolysis is required prior to DNA cleavage. Our aims were to determine if enhanced proteolysis is a mechanism causing GDC-mediated apoptosis. In cultured rat hepatocytes exposed to 50 microM GDC for 4 h, nonlysosomal proteolysis increased by 65% compared with controls. The serine protease inhibitor N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK; 100 microM) reduced cell death from apoptosis by 75% after 4 h of treatment with GDC. TLCK also inhibited DNA fragmentation. There was a twofold increase in nuclear serinelike protease activity during GDC-induced apoptosis accompanied by a 2.5-fold reduction in nonnuclear serine protease activity, suggesting translocation of the protease from the cytosol to the nucleus. Zn2+, an inhibitor of apoptosis, also inhibited nonlysosomal proteolysis and nuclear serinelike protease activity. These novel data suggest that nonlysosomal serinelike protease activity contributes to hepatocyte apoptosis. These data may be important in understanding apoptosis in other cell types and in providing insight into the mechanisms of liver injury during cholestasis.

Animals↗
PubMed1995

Lectin-carbohydrate interactions in disease. T-cell recognition of IgA and IgD; mannose binding protein recognition of IgG0.

Two disease associated lectin-carbohydrate interactions have been studied. (1) A T-cell surface lectin which binds IgA1 and IgD is expressed on CD4+ and CD8+ T-lymphocytes in a number of diseases including systemic lupus erythematosus, rheumatoid arthritis (RA), Behcet's disease and IgA nephropathy. We have demonstrated that calcium independent binding to this receptor is mediated by the O-linked disaccharide Gal beta 3GalNAc which is associated with the hinge regions of both IgA1 and IgD. (2) In rheumatoid arthritis the proportion of IgG0 glycoform populations lacking terminal galactose increases. We have shown that terminal GlcNAc residues on oligosaccharides in the Fc region of IgG0 can bind to the C-type lectin, serum mannose binding protein, and thus activate the classical complement pathway. This provides a mechanism of activation of the complement system not available to the other classes of IgG glycoforms.

Carbohydrate Metabolism↗
PubMed1994

Occurrence of Listeria in hot and cold smoked seafood products.

Over a one-year period, 258 samples of smoked fish products were obtained from retail outlets in Newfoundland and processed for Listeria. Of these, 142 were hot smoked and 116 cold smoked, and the samples comprised of nine species of fish. The Canadian FDA listeria isolation protocol consisted of a two-stage enrichment followed by plating on selective isolation media, Oxford, and LPM. An additional selective medium, PALCAM, was also used. Listeria spp. were isolated from 43 of 258 (16.7%) samples processed in all, with hot smoked products yielding 25.4% (36/142) of the isolates, and cold smoked products yielding 6% of the isolates (7/116). Among the nine species tested, cod had the highest rate of Listeria contamination at 46.7%. Of the 43 Listeria spp. isolated, 18 (41.9%) were L. innocua, 13 (30.2%) were L. welshimeri and 12 (27.9%) were L. monocytogenes.

Food Microbiology↗
PubMed1994

Comparison of short and long-term renal function in liver transplant patients receiving cyclosporin or FK 506.

Long-term renal function was compared in 49 liver recipients [25 patients received cyclosporin (CyA) and 24 patients received FK 506] followed for a period of 1 year. Creatinine (CR) and glomerular filtration rate (GFR) pretransplantation (pre-Tx) and at 1, 3, 5, and 12 months post-Tx were recorded, as well as incidences of hyperkalemia, post-Tx hypertension, and insulin-dependent diabetes mellitus (IDDM) in the two groups. At 1 year post-Tx, the mean Cr had risen from baseline by 56% and 60% in the FK and CyA groups, respectively; the mean GFR had dropped by 32% in FK patients and by 27% in CyA patients. Acute nephrotoxicity occurred in 7/25 CyA patients (2/7 required dialysis) and 9/26 FK patients (7/9 required dialysis; 2/7 were switched to CyA). None remained on dialysis at 3 months. Renal insufficiency persisted at 1 year in 7/16 patients with early toxicity (CyA, 4; FK, 3) and in 3 of the remaining 36 pts (P < 0.001). Hyperkalemia occurred in 4/25 CyA, and in 12/24 FK patients (P < 0.025), post-Tx hypertension occurred in 15 CyA, and 7 FK patients (P < 0.05), and IDDM occurred in 4 CyA and 7 FK patients (P = ns). FK 506 and CyA, thus, exerted similar chronic renal effects. Although acute renal insufficiency improved upon dose reduction, renal impairment was permanent in some cases.

Creatinine↗
PubMed1994

Increases of intracellular magnesium promote glycodeoxycholate-induced apoptosis in rat hepatocytes.

Retention of bile salts by the hepatocyte contributes to liver injury during cholestasis. Although cell injury can occur by one of two mechanisms, necrosis versus apoptosis, information is lacking regarding apoptosis as a mechanism of cell death by bile salts. Our aim was to determine if the bile salt glycodeoxycholate (GDC) induces apoptosis in rat hepatocytes. Morphologic assessment included electron microscopy and quantitation of nuclear fragmentation by fluorescent microscopy. Biochemical studies included measurements of DNA fragmentation, in vitro endonuclease activity, cytosolic free Ca2+ (Cai2+), and cytosolic free Mg2+ (Mgi2+). Morphologic studies demonstrated typical features of apoptosis in GDC (50 microM) treated cells. The "ladder pattern" of DNA fragmentation was also present in DNA obtained from GDC-treated cells. In vitro endonuclease activity was 2.5-fold greater with Mg2+ than Ca2+. Although basal Cai2+ values did not change after addition of GDC, Mgi2+ increased twofold. Incubation of cells in an Mg(2+)-free medium prevented the rise in Mgi2+ and reduced nuclear and DNA fragmentation. In conclusion, GDC induces apoptosis in hepatocytes by a mechanism promoted by increases of Mgi2+ with stimulation of Mg(2+)-dependent endonucleases. These data suggest for the first time that changes of Mgi2+ may participate in the program of cellular events culminating in apoptosis.

Animals↗
PubMed1994

Preservation injury in clinical liver transplantation: incidence and effect on rejection and survival.

The distribution of the severity of preservation injury (PI), its association with acute early rejection, and its effect on graft and patient survival were examined in 151 patients transplanted between 9/88 and 12/91. PI was graded into mild, moderate and severe using prothrombin time (PT) on the 2nd POD and peak AST and ALT levels of the first 3 days after transplant. Of the 151 patients, 104 (68.8%) had minimal, 24 (15.9%) had moderate, and 23 (15.3%) had severe PI. The rate of early rejection, within 21 days after transplant, (54.8% vs 54.2% vs 52.2%) and its timing (10.0 +/- 0.5 vs 8.8 +/- 0.8 vs 8.9 +/- 1.4 days) as well as the incidence of steroid-resistant rejection (21.4% vs 33% vs 30%) did not differ significantly among groups. Graft survival was significantly lower in the severe PI group than among patients with minimal PI at 3 months and 24 months (65.2% vs 86.2%; p < 0.05 and 58.3% vs 82.7%; p < 0.05, respectively). Patient survival at 3 and 24 months was similar among the groups (91.1% vs. 95.8% vs 86.9% and 81.9% vs 91.1% vs. 74.3%). We conclude that the cellular damage associated with preservation injury does not predispose to development of acute rejection.

Alanine Transaminase↗
PubMed1994

A human T-cell receptor recognizes 'O'-linked sugars from the hinge region of human IgA1 and IgD.

A receptor which binds secretory IgA (sIgA) is expressed on human T cells from patients with systemic lupus erythematosus, rheumatoid arthritis, Behcet's syndrome and IgA nephropathy and on normal T cells following phytohaemagglutinin (PHA) stimulation. The specificity of this receptor was initially probed with a panel of normal serum immunoglobulins in competitive inhibition assays with sIgA using two-colour immunofluorescence. While the receptor showed the strongest affinity for IgA1 (IC(50)10(-6) M), IgD which has a similarly glycosylated hinge region to IgA1, also bound to the receptor (IC50 10(-5) M). IgA2, which lacks the 'O'-glycosylated hinge region, did not significantly inhibit the binding at these concentrations suggesting that the IgA determinants for this receptor might be the oligosaccharides present in the hinge region of IgA1. IgA1 has up to 10 'O'-linked oligosaccharides and four N-linked oligosaccharides per molecule. In order to probe the role of the 'O'-linked hinge sugars in the binding event, a sugar library was prepared from IgA1 by a procedure designed to release 'O'-linked oligosaccharides preferentially, and to retain them in the natural closed ring formation. The sugars were released by hydrazinolysis at 65 degrees and the resulting oligosaccharide library analysed by high voltage paper electrophoresis (HVE) and P4 gel permeation chromatography. Competitive inhibition studies demonstrated that both the library and the individual 'O'-linked sugars associated with IgA1 were implicated in the binding of IgA1 to this receptor (IC50 between 1 x 10(-5) M and 6 x 10(-5) M). Within this range the individual sugars showed small differences in their affinity for the receptor in the following order: Gal beta 3GalNAc = NeuNAc2 alpha 3(6)Gal beta 3GalNAc > NeuNAc2 alpha 3(6)Gal beta 3[NeuNAc2 alpha 6]GalNAc > or = GalNAc.

Binding, Competitive↗
PubMed1993

Use of hydrazine to release in intact and unreduced form both N- and O-linked oligosaccharides from glycoproteins.

The use of hydrazine to release unreduced N- and O-linked oligosaccharides from glycoproteins has been investigated using several "standard" glycoproteins of previously defined glycosylation. It is shown that hydrazinolysis can be used to release intact N- and O-linked oligosaccharides in an unreduced form. The release of O-linked oligosaccharides occurs with a lower temperature dependence than the release of N-linked oligosaccharides, and the kinetic parameters governing release of oligosaccharides from these standard glycoproteins have been determined. These parameters allow a definition of reaction conditions under which anhydrous hydrazinolysis can be used to selectively release O-linked oligosaccharides (60 degrees C, 5 h) or release both N- and O-linked oligosaccharides (95 degrees C, 4 h) in high yield (> 85%) from all glycoproteins investigated (n = 11). Under these reaction conditions, the recovered N- and O-linked oligosaccharides are structurally intact (as judged by 600-MHz 1H-NMR, laser-desorption mass spectrometry, HPAEC-PAD, gel filtration, and glycosidase digestion), with the possible exception of certain N- and O-acyl substituents of sialic acid. This use of mild hydrazinolysis therefore allows both the simultaneous and sequential chemical release from glycoproteins of O- and N-linked oligosaccharides in their intact unreduced form.

Animals↗
PubMed1993

Effect of culture conditions on IgM antibody structure, pharmacokinetics and activity.

Culture conditions affect the binding activity, charge heterogeneity, conformational stability, glycosylation, and pharmacokinetics of human monoclonal IgM HMAB-10058. The 10058 human/human/murine trioma was grown in serum-free airlift suspension culture, hollow fiber perfusion culture, or in nude mouse ascites. The ascites-produced antibody showed reduced conformational stability, greater charge and glycoform heterogeneity, and a lower average degree of sialylation than the in vitro culture-produced material. Mean residence time after IV injection in rats was approximately 80-fold greater for the ascites culture-produced material, but specific binding activity was less than 5% of that for the airlift-produced material. In vitro culture in serum-supplemented media (in a hollow fiber perfusion reactor or in shake-flasks) resulted in antibody with pharmacokinetics intermediate between the serum-free airlift and ascites-produced materials. Incubation of airlift-produced antibody in ascites fluid also resulted in material with intermediate pharmacokinetics. Conclusions regarding the effect of culture conditions on antibody product cannot be generalized, as in vitro-produced antibody derived from two related cell lines (HMAB-10233 and HMAB-10390) had long mean residence times similar to that of ascites-produced HMAB-10058.

Animals↗