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Biomedical subjects

J Mathew

Publications and source records attributed to J Mathew.

At least 37 records · Page 2Linked to original sources
PubMed1994

Changes in Na-K ATPase and protein kinase C activities in peripheral nerve of acrylamide-treated rats.

In previous studies on rat peripheral nerve, we showed that acrylamide (ACR) exposure was associated with alterations in axonal and Schwann cell elemental composition that were consistent with decreased Na-K ATPase activity. In the present corollary study, the effects of ACR exposure on Na-K ATPase activity were determined in sciatic and tibial nerves. Subacute ACR treatment (50 mg/kg/d x 10 d, ip) significantly (p < .05) decreased Na-K ATPase activity by 45% in sciatic nerve but did not affect this activity in tibial nerve. Subchronic ACR treatment (2.8 mM in drinking water for 30 d) significantly decreased (p < .05) Na-K ATPase activities by 19% and 35% in sciatic and tibial nerves, respectively. Na-K ATPase activity was not altered in sciatic nerve homogenates exposed to 1.0 mM ACR in vitro. Since protein kinase C (PKC) has been proposed to play a role in the modulation of membrane Na-K ATPase function, PKC activity was also measured in sciatic nerve homogenates and subcellular fractions prepared from control and ACR-treated rats. Regardless of the ACR treatment protocol, PKC activity was elevated in nerve cytosol, but not in a particulate fraction. The results of this study suggest that decreased Na-K ATPase activity is involved in ACR-induced perturbation of axoplasmic and Schwann cell elemental composition in rat peripheral nerves and that loss of activity is not due to direct chemical inhibition of the enzyme. The role of PKC in ACR neurotoxicity requires further elucidation.

Acrylamide↗
PubMed1994

Quantitative analysis of macrophages and perisinusoidal cells in primary biliary cirrhosis.

Immunohistochemistry and image analysis were used to quantify alterations in the Kupffer cell and 'activated' perisinusoidal cell populations in the different stages of primary biliary cirrhosis. Anti-CD68 macrophage antibodies were used to detect Kupffer cells, and anti-alpha-smooth muscle actin (alpha-SMA), PR 2D3 and anti-desmin antibodies to detect perisinusoidal cells. Liver biopsy material was available from 26 patients with primary biliary cirrhosis and 23 patients with histologically normal liver. Increased Kupffer cell numbers were observed in periportal/periseptal zones of stage 3 primary biliary cirrhosis (n = 9), and in random parenchymal areas of stage 3 and stage 4 cases. Significantly increased 'activated' perisinusoidal cell numbers were seen only in periportal/periseptal zones of stage 3 and stage 4 primary biliary cirrhosis. Neither Kupffer cell nor perisinusoidal cell numbers altered significantly in stage 1 and 2 primary biliary cirrhosis (n = 6). PR 2D3 positivity and increased alpha-SMA immunoreactivity by perisinusoidal cells in primary biliary cirrhosis support myofibroblastic differentiation of these cells. Human perisinusoidal cells, unlike their rodent counterparts, did not express desmin in primary biliary cirrhosis or control liver. Kupffer cells and 'activated' perisinusoidal cell accumulation in periportal/periseptal zones of the precirrhotic and cirrhotic primary biliary cirrhosis liver support the concept of Kupffer cell-mediated stimulation of perisinusoidal cells. Furthermore, these findings indicate that Kupffer cell-perisinusoidal interactions play an important role in the development of liver fibrosis and cirrhosis in primary biliary cirrhosis.

Actins↗
PubMed1994

Post-infantile giant cell hepatitis: histological and immunohistochemical study.

AIM: To determine the composition of the inflammatory infiltrate and to check for the presence of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in nine cases of post-infantile giant cell hepatitis. METHODS: The clinical, serological, and histological features of the nine cases were reviewed. Immunohistochemistry was used on liver biopsy specimens from six cases to: (i) characterise the lymphocytic infiltrate; (ii) assess the monocyte/macrophage response; (iii) detect "activated" perisinusoidal cells; and (iv) detect CMV and EBV antigens. Electron microscopic examination was carried out in two cases. RESULTS: Four patients had serological features suggestive of autoimmune chronic active hepatitis; in the other five cases the aetiology was obscure. Two patients presented with neurological symptoms. Hepatitis resolved completely in one patient; two patients showed clinical improvement; and one remained stable. Cirrhosis developed in three patients, one of whom proceeded to liver transplantation, and three patients died. Portal inflammation was present in all cases and lymphocytic piecemeal necrosis in eight cases, but intra-acinar inflammation associated with hepatocyte necrosis was observed in only five cases. The inflammatory infiltrate was composed predominantly of T lymphocytes; an increase in monocyte/macrophage cells was also observed. Mallory bodies, often with associated neutrophilic infiltrate, were present in four cases, and bilirubinostasis was a feature in four cases. "Activated" perisinusoidal cells were present, especially in relation to areas of inflammation, necrosis, and fibrosis. There was severe fibrosis or cirrhosis in five cases. Paramyxoviral nucleocapsids were not seen in the two cases examined ultrastructurally. CONCLUSIONS: Post-infantile giant cell hepatitis should be viewed as a heterogeneous clinical and aetiological entity encompassing cases of hepatitis with extensive giant cell hepatocyte transformation.

Adult↗
PubMed1994

An initial multicenter, randomized controlled trial on the safety and efficacy of acadesine in patients undergoing coronary artery bypass graft surgery. SPI Research Group.

Acadesine (5-amino-4-imidazole carboxamide riboside) is a purine nucleoside analog that has been shown in animals to reduce myocardial ischemic injury by selectively increasing the availability of adenosine in ischemic tissues. Because patients undergoing coronary artery bypass graft (CABG) surgery are especially vulnerable to developing myocardial ischemia, we investigated whether perioperative use of this adenosine-regulating drug with potential anti-ischemic properties could modify the incidence and severity of perioperative myocardial ischemia. The goals of this study were to evaluate safety and the effects of acadesine on myocardial ischemia, left ventricular function, and, secondarily, on adverse clinical outcomes (myocardial infarction, heart failure, life-threatening dysrhythmias, and death) in patients undergoing CABG surgery. One hundred sixteen patients were randomized to receive one of three continuous intravenous dosing regimens (placebo [control] or one of two doses of acadesine [high- and low-dose infusion]) in double-blind fashion intraoperatively and in the early postoperative period (total infusion time was 7 h). Multidose cold crystalloid cardioplegia (each containing either acadesine or placebo) was used for myocardial protection. All were monitored for potentially drug-related adverse events and the presence of myocardial ischemia was assessed by continuous Holter electrocardiography (ECG) and transesophageal echocardiography (TEE). All patients received standardized anesthetic, surgical, and hemodynamic management during the intraoperative period. All research data (ECG, TEE, outcome data) were evaluated at the coordinating center (San Francisco) in blinded fashion to ensure that uniform data analysis criteria were employed. The administration of acadesine was safe: mild increases in plasma uric acid (a metabolite of acadesine) occurred only in patients receiving high doses (mean increase 1.6 +/- 0.2 mg/dL) and were without clinical sequelae. Before drug administration in the preoperative period (baseline), the incidence and severity of ECG ischemia did not differ among the three groups (placebo = 18%; low-dose = 14%; high-dose = 14%). During prebypass, the incidence of ECG ischemia was similar in all three groups (0%, 3%, 3%, respectively). The incidence of TEE ischemia was numerically lower in the two acadesine groups (high-dose = 6%, low-dose = 15%) than in the control group (19%), but this was not statistically significant (P = 0.22). During postbypass, the incidence of ECG ischemia was 11% in the high-dose group, 22% in the low-dose group, and 18% in the control group (P = 0.42), and TEE ischemia was similar in incidence in all groups (placebo = 29%; low dose = 27%; high-dose = 24%) (P = 0.86).(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1994

Developing strategies to prevent inhospital cardiac arrest: analyzing responses of physicians and nurses in the hours before the event.

OBJECTIVES: To determine: a) the frequency of premonitory signs and symptoms before cardiac arrest in patients on the general medical wards of a hospital; b) any characteristic patterns in nurse and physician responses to these signs and symptoms; and c) whether cardiac arrests on the ward occur more frequently in patients discharged from the medical intensive care unit (ICU) than in other patients. DESIGN: Case series of consecutive patients who had an inhospital cardiac arrest over a 20-month period. SETTING: General medical wards of a 1,000-bed urban public hospital. PATIENTS: There were 21,505 total admissions to the medical service in this period. Patients whose cardiac arrests occurred in the Emergency Room and ICU and patients with do-not-resuscitate orders were excluded from the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were a total of 150 cardiac arrests on the medical wards (cardiac arrest rate: 7.0/1,000 patients) with a hospital mortality rate of 91%. In 99 of 150 cases, a nurse or physician documented deterioration in the patient's condition within 6 hrs of cardiac arrest. Common findings included: a) failure of the nurse to notify a physician of a deterioration in the patient's mental status; b) failure of the physician to obtain or interpret an arterial blood gas measurement in the setting of respiratory distress; and c) failure of the ICU triage physician to stabilize the patient's condition before transferring the patient to the ICU. Former ICU patients (cardiac arrest rate: 14.7/1,000 patients) were more likely to suffer cardiac arrest than other patients (cardiac arrest rate: 6.8/1,000 patients) (p = .004). CONCLUSIONS: Cardiac arrests on the general wards of the hospital are commonly preceded by premonitory signs and symptoms. Strategies to prevent cardiac arrest should include training for nurses and physicians that concentrates on cardiopulmonary stabilization and how to respond to neurologic and respiratory deterioration. Special attention should also be devoted to patients who have been discharged from the ICU who are at greater risk for cardiac arrest after ICU discharge than are other medical patients.

Clinical Competence↗
PubMed1993

Study of blood compatible polymers. III. Copolymers of N-benzyl, N-(2-hydroxyethyl) acrylamide and 2-hydroxyethyl methacrylate.

Copolymerization of 2-hydroxyethyl methacrylate (HEMA) and N-benzyl, N-(2-hydroxyethyl) acrylamide (BENAAm) was carried out at different mole ratios of the monomers to obtain copolymers of varying composition. BENAAm content of the copolymers varies between 13 and 70%. Investigation of the interaction of rabbit platelets with these polymer surfaces showed that copolymers with higher BENAAm content inhibit the platelet deformation. Human umbilical cord fibroblast cells proliferated very well on the copolymer surfaces. The cell growth rate on polyHEMA was relatively low. Maximum cell growth was observed on the copolymer having 87% HEMA.

Acrylic Resins↗
PubMed1993

A 34-kd protein with strong homology to ras-like proteins inhibits epidermal growth factor activity.

Epidermal growth factor (EGF) and its analog, transforming growth factor-alpha, are felt to be important in oncogenesis. When malignant rabbit fibroma virus infects RK-13 rabbit kidney cells, a 34-kd protein that inhibits the effects of EGF on certain target cell lines is produced. We have purified this protein using high-pressure liquid chromatography and gel electrophoresis. This purified protein abolishes EGF-induced cellular proliferation. It also causes the EGF receptor-bearing A431 carcinoma cell line to stop proliferating in vitro. This purified 34-kd EGF inhibitor (EGFI) redirects cellular protein phosphorylation in the presence or absence of EGF. Whereas EGF increases phosphorylation of cellular proteins in normal rat kidney cells, clone 49F, and A431 EGFI generally decreases it. Both EGF and EGFI cause increased protein production in A431 and normal rat kidney cells. The major species of protein synthesized by cells seem invariant to EGFI, with or without EGF. The partial protein sequence of two fragments of EGFI shows striking similarity to two ras like proteins. Possible means by which such a ras-like protein might inhibit EGF-induced cellular proliferation are discussed. Therefore, a purified 34-kd ras-like protein inhibits EGF-induced cellular proliferation and changes the targets for cellular protein phosphorylation. Studies are in progress to characterize this protein further, both structurally and functionally.

Amino Acid Sequence↗
PubMed1992

Cardiopulmonary bypass induces leukocyte-platelet adhesion.

Cardiopulmonary bypass (CPB) has been demonstrated to activate platelets, producing an increased number of circulating platelets that have undergone alpha-granule release and express granule membrane protein-140 (GMP-140) on their surface. In vitro, GMP-140 mediates activated platelet adhesion to neutrophils (PMN) and monocytes, causing the formation of leukocyte-platelet conjugates. Using a newly developed assay that measures the percentage of circulating leukocyte-platelet conjugates in whole blood, we studied 17 patients undergoing CPB and have determined that (1) monocyte-platelet conjugates increased significantly during CPB, from 18% +/- 1.5% to 44% +/- 4.5% (mean +/- SEM) by the end of CPB, while PMN-platelet conjugates increased only slightly and lymphocyte-platelet conjugates decreased; (2) the time course of the increase in monocyte- and PMN-platelet conjugates paralleled that of the increase in circulating activated platelets, as determined by the presence of surface GMP-140; and (3) monocyte activation, as assessed by increased surface expression of CD11b, showed a gradual increase similar to the increase in monocyte-platelet conjugates, while PMN surface CD11b peaked immediately after the start of CPB. We conclude that CPB, through increased platelet GMP-140 expression, causes formation of monocyte-platelet, and to a lesser extent, PMN-platelet conjugates. The activation of monocytes and PMN on CPB, as evidenced by CD11b expression, occurs with differing time courses.

Blood Platelets↗
PubMed1992

Activity and distribution of phosphoinositidase C in rat sciatic nerve.

The hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) by rat sciatic nerve cytosolic phosphoinositidase C [phosphoinositide-specific phospholipase C (PIC)] was studied at neutral pH and at ionic concentrations that approximate intracellular conditions. The principal water-soluble product formed was shown to be inositol trisphosphate by anion exchange chromatography. The maximum hydrolysis rate (2.5 nmol/min/mg protein) was achieved at less than 100 nM Ca2+. Hydrolysis was markedly increased to 15 nmol/min/mg protein by inclusion of K+ in the reaction mixture. In the presence of 200 mM K+, the optimum Ca2+ was increased to approximately 600 nM. Higher Ca2+ concentrations progressively inhibited PIP2 hydrolysis. Mg2+ also inhibited the reaction, but the presence of equimolar amounts of ATP and Mg2+ had no effect. Appreciable degradation of phosphatidylinositol-4-phosphate (PIP) also occurred in the nanomolar Ca2+ range, whereas breakdown of phosphatidylinositol (PI) required millimolar Ca2+. The presence of PIP but not PI inhibited PIP2 hydrolysis. Upon subcellular fractionation of nerve, more than 50% of recovered PIC activity was in the cytosol and about 20% was located in a myelin-enriched fraction. Using PIP2 as substrate, PIC activities in nerves from normal and streptozotocin-induced diabetic animals were not different. However, the myelin-associated enzyme from diabetic animals was more labile to freezing and thawing.

Animals↗
PubMed1992

c-erbB-2 oncogene expression in hepatocellular carcinoma and cholangiocarcinoma.

The c-erbB-2 proto-oncogene encodes a transmembrane protein which is homologous to the epidermal growth factor receptor. This protein can be localized immunohistochemically in formalin-fixed paraffin-embedded material using a monoclonal antibody NCL-CB11; positive membrane staining correlates with gene amplification and protein overexpression in breast cancer. Using this technique we have shown that only 2/26 (8%) of hepatocellular carcinomas, 0/10 (0%) of cholangiocarcinomas and 0/2 (0%) hepatoblastomas overexpressed c-erbB-2 as evidenced by membrane staining. Moreover c-erbB-2 mRNA was not detected in seven hepatocellular carcinomas examined by Northern blot analysis. c-erbB-2 overexpression is, therefore, unlikely to be contributing to the malignant phenotype in hepatocellular carcinoma and cholangiocarcinoma.

Adenoma, Bile Duct↗
PubMed1992

Glutathione S-transferases in neonatal liver disease.

AIMS: To investigate the distribution of alpha and pi class glutathione S-transferases (GST) in normal fetal, neonatal, and adult liver; and to examine changes in GST expression in neonatal liver disease. METHODS: alpha and pi class GST were immunolocalised in sections of formalin fixed liver tissue obtained from human fetuses (n = 21), neonates (n = 8), young children (n = 9) and adults (n = 10), and from neonates with extrahepatic biliary atresia (n = 15) and neonatal hepatitis (n = 12). Monospecific rabbit polyclonal antibodies were used with a peroxidase-antiperoxidase method. RESULTS: Expression of pi GST was localised predominantly within biliary epithelial cells of developing and mature bile ducts of all sizes from 16 weeks' gestation until term and in neonatal and adult liver. Coexpression of pi and alpha GST was seen in hepatocytes of developing fetal liver between 16 and 34 weeks' gestation. Although pi GST was seen in occasional hepatocytes up to six months of life, this isoenzyme was not expressed by hepatocytes in adult liver. By contrast, alpha GST continued to be expressed by hepatocytes in adult liver; this isoenzyme was also seen in some epithelial cells of large bile ducts in adult liver. No change was observed in the distribution of alpha GST in either neonatal hepatitis or extrahepatic biliary atresia. However, aberrant expression of pi GST was identified in hepatocytes of all but one case of extrahepatic biliary atresia but in only two cases of neonatal hepatitis. CONCLUSIONS: The phenotypic alterations noted in extrahepatic biliary atresia may result from the effect of cholate stasis. Evaluation of the pattern of pi and alpha GST distribution by immunohistochemical staining may provide valuable information in distinguishing between these two forms of neonatal liver disease.

Adult↗
PubMed1991

Obliterative otosclerosis.

An analysis of 420 consecutive cases of obliterative otosclerosis seen in the Christian Medical College Hospital, Vellore is presented. The proportion of truly obliterative otosclerosis is 33.09 per cent (139 ears). Our male to female ratio in truly obliterative otosclerosis is 1.48:1, while in the non-obliterative group it is 1.34:1. The mean age at onset in the obliterative group was 19.14 while in the non-obliterative group it was 25.60. This is statistically significant (P less than 0.001). The age at presentation was 25.90 in the obliterative group while in non-obliterative group it was 30.86; this is also statistically significant (P less than 0.001). However the time interval between the age at onset and the age at presentation is not statistically significant.

Adolescent↗
PubMed1991

EDTA and EGTA stimulate 36Cl- uptake into rat brain synaptoneurosomes.

Addition of EDTA (0.5-10 mM) to rat brain synaptoneurosomes stimulated rapid, concentration-dependent uptake of 36C1-. Chloride uptake stimulated by EDTA was additive with the 36C1- uptake induced by the GABAA agonist, muscimol, and was not blocked by the GABA-antagonist, picrotoxin, the glycine antagonist, strychnine or the loop diuretic, furosemide. However, the chloride transport inhibitor DIDS completely antagonized 36C1- uptake. EDTA-induced 36C1- uptake varied across brain regions as follows: Striatum greater than hippocampus greater than cerebellum greater than tectum greater than cerebral cortex greater than brain stem greater than hypothalamus. EDTA-induced 36C1- uptake was also present in liver tissues. EDTA analogues, EGTA and CDTA, also stimulated uptake. Although the effect of EDTA was dependent on the presence of extravesicular Ca2+ (0.01-10 mM) this action did not appear to be due to Ca2+ chelation since BAPTA, arsenazo III and citrate were ineffective. These results suggest that EDTA stimulates 36C1- uptake into brain synaptoneurosomes by a picrotoxin-insensitive, calcium-dependent mechanism that may involve a DIDS sensitive anion exchanger or ion channel.

Animals↗
PubMed1989

Differences in susceptibility of rat liver and brain sialidases to ethanol and gangliosides.

Based on reports that ethanol can decrease the level of sialic acid (SA) (neuraminic acid) in several tissues, we tested the hypothesis that ethanol promotes SA cleavage by enhancing the activity of sialidases (neuraminidases). We also investigated whether brain and liver sialidases have the same response to ethanol and gangliosides, especially since our prior studies have demonstrated that gangliosides could antagonize ethanol-induced behavior. Experiments were conducted on homogenates of brain and liver and of liver slices of adult rats. In liver slices, cleavage of SA did not fall in proportion to the ethanol-induced inhibition of sialidase; in fact, at 0.1 M ethanol, free SA increased, even though sialidase was inhibited. Brain sialidase activity on endogenous sialoglycoconjugates was much more resistant to ethanol than liver sialidase and was fully active even in concentrations as high as 1 M. When gangliosides were incubated with liver slices in the absence of ethanol, sialidase was markedly stimulated. The ethanol-induced inhibition of sialdase in liver slices was mimicked by sorbitol, suggesting that the inhibition may be caused by a shift in redox state as a result of increased NADH. The ethanol metabolite, acetaldehyde, does not seem to be a factor, because sialidase inhibition still occurred when slices were incubated with ethanol containing pyrazole. The results indicate that ethanol promotes the accumulation of free SA in liver without stimulating sialdase; our other work suggests that the cause is an increase in accessibility to sialoglycoconjugates rather than decreased utilization of SA. Brain and liver sialidases clearly respond differently to both ethanol and gangliosides.

Animals↗