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J Mathew

Publications and source records attributed to J Mathew.

At least 19 recordsLinked to original sources
PubMed1996

Analysis of the D1S80 (pMCT118) VNTR locus polymorphism in a native Kuwaiti population by the polymerase chain reaction.

We have determined the allele and genotype frequencies at the hypervariable locus D1S80 in a native Kuwaiti population using the polymerase chain reaction technique and subsequent high resolution gel electrophoresis. In a sample of 200 individuals, 21 alleles and 57 genotypes were detected. The alleles with 18 and 24 repeat units were most common with frequencies of 0.188 and 0.408 respectively. The distribution of the observed genotypes was in agreement with the Hardy-Weinberg equilibrium prediction. The observed heterozygosity for the population sample was 0.80 with the allelic diversity of 0.781 +/- 0.029 and the power of discrimination was 0.94. The data obtained in this study are potentially useful for individual identification in forensic casework.

Alleles↗
PubMed1995

HLA-DQ alpha allele and genotype frequencies in a native Kuwaiti population.

We report the allele and genotype frequencies in a sample of an unrelated native Kuwaiti population determined by the use of polymerase chain reaction (PCR) and reverse dot-blot analysis. This technique, involving the use of commercially available AmpliType HLA-DQ alpha forensic DNA amplification and typing kit, has permitted the definition of six alleles and 21 genotypes in a sample of 220 people. The allelic frequencies are in the range 5.7-27.5%. This locus demonstrated a heterozygosity of 0.80 with an allelic diversity of 0.81 and the power of discrimination (PD) was 0.93. The distribution of observed genotypes conformed to Hardy-Weinberg equilibrium thus indicating genetic equilibrium of the different variants. This population data should permit the use of HLA-DQ alpha marker for individual identification in forensic casework.

Alleles↗
PubMed1995

THP-1 macrophage membrane-bound plasmin activity is up-regulated by transforming growth factor-beta 1 via increased expression of urokinase and the urokinase receptor.

Receptors for urokinase (uPA) and plasminogen provide a mechanism to direct the cellular activation of plasminogen. The regulation of these receptors is important for several macrophage functions. In these studies, the effect of transforming growth factor-beta 1 (TGF-beta 1) on uPA, uPA receptor, and plasminogen receptor expression by human THP-1 macrophage was examined. TGF-beta 1 induction of uPA expression by THP-1 cells was differentiation dependent. Suspension and adherent cultures expressed similar constitutive levels of uPA. Exposure of adherent cells to TGF-beta 1 led to a dose- and time-dependent increase in uPA activity which was paralleled by an increase in uPA antigen and uPA mRNA. In contrast, uPA expression by suspension cultures was unresponsive to TGF-beta 1. The differential response exhibited by suspension and adherent THP-1 cells may reflect differences in their expression of TGF-beta 1 receptors, since when assayed by crosslinking techniques, suspension cells primarily expressed a 65 kDa receptor; whereas, the adherent cells expressed 65 and 100 kDa receptors. TGF-beta 1-induced alterations in uPA receptor expression by adherent THP-1 cells were examined by quantitating membrane-bound uPA activity. Membrane-bound uPA activity increased three-fold when cells were incubated with TGF-beta 1. The increase in membrane-uPA activity expressed by TGF-beta 1-treated cells was not due to increased uPA receptor occupancy since incubation of either control or TGF-beta 1 primed cells with exogenous uPA did not lead to an increase in membrane-bound uPA activity. Furthermore, immunoreactive uPA receptor was increased in TGF-beta 1-treated cells. Following incubation with plasminogen, membrane-bound plasmin activity increased three-fold in TGF-beta 1-treated cells. However, no change in immunoreactive membrane-bound plasmin(ogen) was observed. In addition, binding of 125I-Lys-plasminogen to THP-1 cells was not affected by TGF-beta 1 treatment. We conclude that TGF-beta 1 stimulates membrane-bound plasmin activity, without affecting plasminogen receptor expression, through the up-regulation of uPA and the uPA receptor expression.

Cell Adhesion↗
PubMed1995

Results of surgical treatment for infective endocarditis in intravenous drug users.

OBJECTIVE: To determine the early and late results of surgical treatment for infective endocarditis (IE) in intravenous drug users (IVDU). DESIGN: Cohort study of consecutive IVDUs undergoing surgical treatment for IE. SETTING: Large public hospital serving the urban population of Chicago, Ill. PATIENTS: Consecutive IVDUs operated on between July 1982 and June 1991 for IE. MAIN OUTCOME MEASURES: Death, stroke, noncerebral systemic embolization, major bleeding, recurrent endocarditis, and repeated valve replacement. RESULTS: There were 80 patients, 58 men and 22 women, with a mean age of 37.5 +/- 10 (SD) years. The hospital course in all patients and follow-up data on 75 (94%) patients were complete. The primary indication for surgery was acute congestive heart failure in 44 (56%), persistent sepsis in 21 (26%), and multiple systemic embolization in 15 (19%) patients. Six patients (7.5%) died within 30 days of surgery. An additional 13 of 69 patients (17.6%) died during the follow-up, 8 from cardiovascular causes. The probability of survival at 36 months and at 60 months was 0.74 +/- 0.05 (SE) and 0.70 +/- 0.05, respectively. Seventeen (30%) of the survivors had at least one major cardiovascular event; 6 (8.8%) had recurrent endocarditis, 4 (5.8%) had stroke, 3 (4.4%) had extracerebral bleeding, 1 had extracerebral systemic embolism, and 3 (4.4%) required repeated valve replacement. Probability of event-free survival at 36 months and 60 months was 0.65 +/- 0.06 and 0.52 +/- 0.08, respectively. The median duration of event-free survival was 65 months. CONCLUSION: Since the expected mortality without surgery in patients with IE in whom medical treatment fails is almost 100%, it is concluded that surgical treatment is indicated for, and substantially improves the outlook for early and late survival of, IVDUs with IE who fail to respond to medical management.

Adult↗
PubMed1994

Regulation of macrophage receptor-bound plasmin by autoproteolysis.

The activation of plasminogen by macrophage is regulated by their expression of receptors for urokinase and plasmin(ogen). In these studies we have examined plasmin(ogen) binding to adherent human THP-1 macrophage. Plasmin bound to the THP-1 cells in a time- and dose-dependent manner (Kd 15.8 +/- 6.2 nM; Bmax 1.4 +/- 0.3 x 10(6)/cell). The lysine analog epsilon-aminocaproic acid competitively inhibited plasmin binding. The fraction of membrane-bound plasmin, however, became increasingly resistant to displacement with epsilon-aminocaproic acid. Over a 24-h period, membrane-bound plasmin activity fell 80% despite the presence of catalytically active plasmin in the incubation media. The loss of receptor-bound plasmin activity was not due to proteolytic alterations of its receptor since 125I-Lys-plasminogen bound to THP-1 cells pretreated with plasmin with similar affinity as to untreated cells. Following a 24-h incubation of 125I-Lys-plasminogen or 125I-plasmin with THP-1 cells, several degradative fragments were apparent in their conditioned media. The smaller degradative fragments (28 and 36 kDa) lacked cell binding activity and were demonstrated to be active by casein-zymography. A 48-kDa fragment bound to cells in a lysine-dependent manner but was not active. In contrast, phenylmethylsulfonyl fluoride-inactivated 125I-plasmin retained its binding activity over 24 h, and degradative fragments were not present in the conditioned media. The binding of 125I-Lys-plasmin(ogen) to THP-1 cells was also examined in the presence of excess alpha 2 plasmin inhibitor. Despite the absence of fluid-phase plasmin activity, membrane-bound 125I-Lys-plasmin(ogen) decreased over 24 h. At 24 h a radiolabeled 48-kDa fragment was observed in the conditioned media and together with 125I-Lys-plasmin(ogen) was bound to cells. Unlike 125I-Lys-plasmin, the 48-kDa fragment did not form a complex with alpha 2 plasmin inhibitor. Thus, autoproteolysis of receptor-bound plasmin results in fragments with truncated physiologic properties that possess either cell binding or catalytic activities. We propose that autoproteolysis is a mechanism for regulating membrane-bound plasmin activity.

Catalysis↗
PubMed1994

Guanosine-5'-(3-O-thio)triphosphate-mediated stimulation of phosphoinositidase C in solubilized rat peripheral nerve myelin and its alteration in streptozotocin-induced diabetes.

The regulation of phosphoinositidase C (PIC) activity by guanosine-5'-(3-O-thio)triphosphate (GTP gamma S) was characterized in a cholate-solubilized peripheral myelin-enriched fraction from rat sciatic nerve. The GTP analog maximally enhanced PIC-catalyzed hydrolysis of exogenous phosphatidylinositol-4,5-bisphosphate (PIP2) in a dose-dependent manner only within a narrow range of cholate concentrations. Maximal stimulation was attained at 0.6 microM GTP gamma S and could be completely prevented by 1 microM guanosine-5'-(2-O-thio)diphosphate. Neither adenylyl-imidodiphosphate nor adenosine triphosphate (ATP) enhanced PIC activity. Carbamoylcholine (1 mM) added together with GTP gamma S increased the extent of PIP2 hydrolysis over that elicited by GTP gamma S alone and this stimulation was blocked by the muscarinic receptor antagonist, atropine (50 microM). In detergent-solubilized myelin preparations from streptozotocin-induced diabetic rats, a higher concentration of the guanine nucleotide analog was required to achieve stimulation comparable to that obtained with corresponding preparations from normal animals. These results suggest that sciatic nerve myelin possesses muscarinic receptors coupled via a GTP-binding protein to PIC and that this system can be reconstituted in detergent-solubilized extracts. It is possible that the function of G proteins in cell signaling is impaired in experimental diabetic neuropathy.

Adenosine Triphosphate↗
PubMed1994

Gender-specific differences in expression of mRNAs for functional and structural proteins in rat ventricular myocardium.

Sex-related differences in predisposition to heart diseases have long been recognized. The molecular and cellular bases for this difference are unknown. In this study we have compared expression of genes for various structural and functional proteins of muscle and interstitial compartments of the myocardium in the adult and neonatal, male and female rat heart. We have also compared cultured cardiac fibroblasts from male and female hearts with regards to gene expression and proliferative capacity. We showed that in the adult rats, the abundance of mRNAs for contractile proteins alpha- and beta-myosin heavy chain (MHC) is higher in the heart of female rats than in that of age-matched male rats. However, the difference in mRNA level for alpha-MHC was more drastic (736%, P < 0.001) than that for beta-MHC (469%, P < 0.001). mRNA levels for sarcomeric actin in the female heart were greater by 79% (P < 0.001). Collagen type I had a significantly higher (303%, P < 0.01) mRNA level in the female heart compared with the male heart. mRNAs for TGF-beta 1, cytoskeletal actin and connexin 43 were also higher (150%, P < 0.01; 130%, P < 0.01, and 150%, P < 0.01, respectively) in the female heart compared with age-matched male heart. There were no significant sex-related differences at the mRNA levels for the above proteins in ventricular tissue from neonatal male and female littermates. At the cellular level, cardiac fibroblasts obtained from adult and neonatal hearts of both sexes were comparable with respect to the abundance of mRNAs for collagen type I, TGF-beta 1 or cytoskeletal actin. However, DNA synthesis, as measured by [3H]thymidine incorporation, was higher (328%, P < 0.01) in cells from adult female heart compared with that in cells from adult male rat heart. This difference was even more pronounced in cardiac fibroblasts obtained from newborn female rats (933%, P < 0.001) compared with that in cells obtained from newborn male rat hearts. Together, these findings show that there are sex-related differences in gene expression for most major proteins in heart tissue and that this phenomenon is associated with the post-pubertal period. These findings further suggest that sex-related differential gene expression and DNA synthesis in cardiac cells are due to the regulatory effects of male- and female-specific hormones.

Actins↗
PubMed1994

Non-parenchymal cell responses in paracetamol (acetaminophen)-induced liver injury.

We have analysed Kupffer cell and 'activated' perisinusoidal cell populations in liver biopsies from patients with paracetamol (acetaminophen)-induced hepatic necrosis of varying degrees of severity. Kupffer cells were identified immunohistochemically using the monoclonal antibody KPJ and perisinusoidal cells by identification of alpha-smooth muscle actin expression. Material was available from four groups of individuals: (i) 11 cases with mild (grade I) injury; (ii) six cases with moderate (grade II) injury; (iii) six cases with severe (grade III) injury; and (iv) controls with normal liver histology (n = 23). Biopsies in groups (i)-(iii) were obtained within 5 days of drug ingestion. All patients in this study survived and follow-up biopsies were obtained at 4 months, by which time the histological abnormalities had fully resolved. Kupffer cells and perisinusoidal cell numbers were assessed in immunostained preparations of acute and recovery phase biopsies and in control specimens. In acute phase biopsies from patients with grade II and III injury there was expansion of the Kupffer cell and perisinusoidal cell populations within areas of injury. There was a strong correlation between the size of these two cell populations (r = 0.886). No significant difference in cell numbers was found between those with grade I injury and controls. In recovery phase biopsies from patients with paracetamol-induced injury, perisinusoidal cell numbers did not differ significantly from normal controls. Kupffer cells numbers also decreased in recovery phase biopsies compared with the acute phase, although there was persistent expansion of the Kupffer cells population in those who originally had grade III injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
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↗