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Biomedical subjects

N Ahmed

Publications and source records attributed to N Ahmed.

At least 109 records · Page 6Linked to original sources

Telemetry outside critical care units: patterns of utilization and influence on management decisions.

BACKGROUND: Guidelines for the use of telemetry in hospitalized patients have been proposed by the American College of Cardiology (ACC). However, there have been only a few studies which have investigated the usefulness of these guidelines in clinical practice. HYPOTHESIS: This study assessed the role of telemetry in the decision making process outside the critical care units. METHODS: The observational study, lasting 4 weeks, was conducted in the telemetry unit of a tertiary care teaching hospital and included 61 male patients (age range 40-61 years). They had been directly admitted to the telemetry unit or transferred from a critical care unit and were followed for as long as telemetry was active. Indication for telemetry and the contribution of telemetry to management decisions were assessed by a physician not involved in the care of the patient. RESULTS: Cumulative number of telemetry days was 379 with a mean of 6.2 days per patient. Total number of telemetry events was 297. According to the ACC classification, 14 patients (22.9%) had class I indication, 21 patients (34.4%) had class II indication, and 26 patients (42.6%) had class III indication. Telemetry events were seen in 18.2% of class I patients, in 39.7% of class II patients, and in 42.1% of class III patients. Only 12 telemetry events (4%) resulted in patient management, with none belonging to class III. CONCLUSION: Telemetry findings in patients outside the critical care units are not usually responsible for major therapeutic changes. The value of telemetry in such patients may be overrated.

Adult↗

Transforming oncogenes regulate glucose transport by increasing transporter affinity for glucose: contrasting effects of oncogenes and heat stress in a murine marrow-derived cell line.

Transforming oncogenes often overcome the growth factor requirements of cells by activating growth factor signal transduction pathways. Increased energy utilization by transformed cells is a well known phenomenon, but whether glucose uptake is regulated at the level of the glucose transporter has not been clearly established. To determine whether cell transformation by specific oncogenes like, v-H-ras and v-abl affects the activation state of glucose transporters, bone marrow-derived IL-3-dependent 32D (clone3) cells transfected with temperature-sensitive ras and abl oncogenes were used to compare proliferative responses and glucose transporting ability of these cells with the parental cell line at permissive (32 degrees C) and non-permissive (40 degrees C) temperatures. Transformed cells showed elevated incorporation of [3H]thymidine and enhanced tyrosine kinase activity, both of which were abrogated in temperature-sensitive mutants maintained at the non-permissive temperature. Compared with control cells, 2-deoxy-D-[1-(3)H]glucose (2-DOG) uptake was not significantly different in transformed cells at the permissive temperature. However, transformation was associated with a 2-2.5-fold greater affinity of glucose transporters for glucose (Km) and this was reversed following treatment with tyrosine kinase inhibitor, genistein. Maximum velocity of glucose transport (Vmax) and membrane expression of transporters were reduced in oncogene-transformed cells. At the non-permissive temperature, glucose uptake was elevated in both control and oncogene-transformed cells. This increase in glucose transport was not associated with a change in transporter affinity for glucose, but increased Glut-1 expression was observed indicating a 'heat stress' effect that overrode the effects attributable to oncogene loss. The 'heat stress' effect was inhibited by protein synthesis inhibitor cycloheximide. These results provide evidence for intrinsic activation of glucose transporters by the transforming oncogenes ras and abl, and indicate that oncogenes and 'heat stress' regulate glucose transport by different mechanisms.

Animals↗

PCR-based rapid detection of Mycobacterium tuberculosis in blood from immunocompetent patients with pulmonary tuberculosis.

A PCR test based on insertion sequence IS1081 was developed to detect Mycobacterium tuberculosis complex organisms in the peripheral blood. The method was applied to blood samples from immunocompetent individuals with localized pulmonary tuberculosis. Seven of 16 (43.75%) blood samples were found to be positive for the circulating DNA copies of M. tuberculosis complex.

DNA Primers↗

Pathways to mental health care among South African adolescents: analysis of referrals to an adolescent psychiatric unit.

Assessment forms of 670 adolescents referred over four years to an adolescent psychiatric unit were analyzed to establish how they entered mental health care. The first part of the study examined referral sources; the second established the appropriateness of referral. Adolescents were referred via a number of pathways, of which school sources, psychiatric services, and social agencies were prominent. Interestingly, 60.7% of the referrals were from persons not trained in mental health care. No significant difference in appropriateness of referral was found between trained and nontrained sources. Thus, the unique referral base of adolescents in need of mental health care must be recognized. Although the majority in this study were not mental health care workers, the findings show that their referrals were clinically appropriate. This suggests that by improving the mental health skills of this sector, the provision of psychiatric care to adolescents could be enhanced.

Adolescent↗

Coronary thrombosis and the platelet glycoprotein IIIA gene PLA2 polymorphism.

Myocardial infarction results from a platelet-rich occlusive coronary thrombus. Platelet membrane glycoprotein IIb/IIIa plays an important role in platelet adhesion and aggregation. Two polymorphisms of the gene encoding the IIIa subunit. PLA1 and PLA2, have been identified. We investigated the frequency of these polymorphisms in 114 consecutive patients with a history of angina-like chest pain admitted for coronary arteriography. Forty-three of these patients had previously suffered a myocardial infarction. The PLA2 polymorphism was found in 21% of the patients with previous myocardial infarction and in 27% of the patients with angina-like chest pain but no previous myocardial infarction (p = 0.634). There was also no significant association with the extent of coronary disease. There is no evidence, therefore, from this study of an association between the PLA polymorphisms and the occurrence of myocardial infarction.

Adult↗

Acute regulation of glucose transport in a monocyte-macrophage cell line: Glut-3 affinity for glucose is enhanced during the respiratory burst.

Activation of the respiratory burst imposes acute metabolic demands on phagocytic cells. These are met by mobilizing internal energy stores and by increasing the utilization of exogenous energy, including glucose in the circulation. To determine whether the increased glucose uptake that is known to be associated with the respiratory burst involves the regulation of glucose transporter molecules, the intrinsic transport properties of glucose transporters on the macrophage cell line RAW 264.7 were determined after activation with PMA, N-formyl-methionine-leucine-phenylalanine (fMLP) and the cytokines granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3). Treatment with PMA resulted in a 2-fold increase in respiratory burst activity within 10 min; this was associated with a 30-50% increase in 2-deoxyglucose uptake and a 4-fold increase in transporter affinity for glucose. Similarly, fMLP, GM-CSF and IL-3 treatments stimulated 2-deoxyglucose uptake that was associated with a 3-4-fold increase in transporter affinity for glucose. To determine whether the changes observed in 2-deoxyglucose uptake in response to PMA, fMLP and growth factors were influenced by phosphorylation of the sugar, 3-O-methylglucose, which is not phosphorylated, was used. Increased 3-O-methylglucose uptake and increased transporter affinity for glucose were also observed after PMA, fMLP and GM-CSF treatments. Whereas both fMLP and GM-CSF stimulated superoxide production, IL-3 failed to activate respiratory burst activity. The protein kinase inhibitors genistein and staurosporine inhibited the increase in 2-deoxyglucose uptake observed with fMLP and GM-CSF, and partly reversed the affinity increase towards that of untreated control cells. In contrast, the phosphatidylinositol 3-kinase inhibitor wortmannin had little effect on 2-deoxyglucose uptake in response to these activators. Western blotting with subtype-specific antisera showed that Glut-3 was the predominant transporter on RAW 264.7 cells. These studies demonstrate that acute regulation of glucose transporters occurs in response to activators that promote respiratory burst activity, and show that this regulation involves both tyrosine kinases and protein kinase C activity.

3-O-Methylglucose↗

The hemopoietic growth factor, interleukin-3, promotes glucose transport by increasing the specific activity and maintaining the affinity for glucose of plasma membrane glucose transporters.

Most mammalian cells rely on an external supply of glucose for survival, proliferation, and function. Glucose enters cells through specific transporter molecules at the plasma membrane by a facilitative process that does not expend energy. Regulation of glucose transport into cells is thought to occur largely through transporter expression at the cell surface, but the extent to which the intrinsic properties of glucose transporters are regulated is at present controversial. Using a bone marrow-derived cell line that responds to the hemopoietic growth factor, interleukin-3 (IL-3), we investigated IL-3 regulation of glucose transport. IL-3 significantly increased 2-deoxyglucose (2-DOG) uptake within 1 h (26 +/- 8.0%, n = 11) with a maximum 73% increase after 6 h. Withdrawal of IL-3 resulted in decreased uptake within 1 h and this continued to decline to 43% of initial uptake by 16 h. To determine whether these changes in 2-DOG uptake were associated with corresponding changes in glucose transporter expression, subtype-specific antisera against Glut-1 and Glut-3 were used. Little change in membrane expression of these transporters was observed prior to 16 h. Fractionation of cell membranes on Nycodenz gradients showed that the majority of each transporter subtype was associated with the plasma membrane (63-93%) and that transporter distribution did not change markedly in response to addition or withdrawal of IL-3. These results demonstrate that IL-3 regulates glucose uptake by modulating the intrinsic transporting ability of glucose transporters. Decreased transporter affinity for 2-DOG and 3-O-methylglucose was observed following IL-3 withdrawal. Similar affinity changes were observed with 2-DOG following exposure of IL-3-stimulated cells to the protein kinase inhibitors, genistein and staurosporine. In contrast, the tyrosine phosphatase inhibitor, vanadate, acted like IL-3 to increase transporter affinity for glucose. Together these results demonstrate that IL-3 acts to maintain the intrinsic transport properties of glucose transporters without markedly affecting their expression or translocation.

3-O-Methylglucose↗

Immobilisation of whole bacterial cells for anaerobic biotransformations.

Anaerobically grown cells of Escherichia coli were immobilised within a range of entrapment matrices and packed into a column under standard conditions, and the ability of the immobilised cells to reduce nitrite (0.5 mM) was measured at a range of flow rates using sodium formate (20 mM) as the electron donor for nitrite reduction. A flow-rate/activity plot was constructed for each flow-through reactor and RA1/2 values (residence time corresponding to 50% nitrite removal) calculated for each reactor type. Cells immobilised in flat and hollow-fibre membranes were the most effective (RA1/2 = 0.35 h and 0.47 h respectively), with cells entrapped by dialysis membrane (1.53 h), alginate beads (1.93 h), Hypol foam (2.31 h) and polyacrylamide gel (50% nitrite not removed at maximum residence time tested: 4.9 h) performing progressively less effectively. Cells grown as a biofilm on a range of support materials were also tested in comparable packed-bed reactors. Cell loss from these supports was extensive and contributed to poor performance of the reactors despite high initial biomass loadings (RA1/2 values using raschig rings, coke and activated-carbon supports: 1.6 h, 2.3 h and 1.0 h respectively). Biofilms grown on Pharmacia microcarrier supports and used in packed and also fluidised beds were more stable and the performance of these reactors was superior to that of biofilm reactors using other supports, and comparable to that of the membrane reactors (RA1/2 values for Cytoline 2, Cytopore 2 and Cytodex 3: 0.76 h, 0.56 h, 0.68 h respectively).

Acrylic Resins↗

Regulation of glucose transport by interleukin-3 in growth factor-dependent and oncogene-transformed bone marrow-derived cell lines.

Growth factors maintain cell viability and promote cell growth by stimulating glucose transport into cells and by progressing cells through the cell cycle. In the short term, effects on glucose transport involve transporter activation, while in the longer term increased gene expression is involved. This study aimed to investigate growth factor regulation of glucose transport in an interleukin (IL)-3-dependent bone marrow-derived cell line and its oncogene-transformed counterparts. 32D clone 3 (32Dcl3) cells and cells transfected with temperature-sensitive (ts) ras and abl oncogenes, were treated with and without IL-3 and their ability to take up 2-deoxy-D-glucose compared. Transformed cells, which are not dependent on IL-3 for growth at the permissive temperature of 32 degrees C, exhibited a two- to six-fold higher proliferative response, enhanced tyrosine kinase activity and c-myc expression than control cells optimally stimulated with IL-3. Compared with control 32Dcl3 cells, 2-deoxy-D-glucose uptake was also 36-76% higher in transformed cells. The increased glucose uptake in transformed cells was consistent with 2.5-fold higher affinity of the glucose transporters for glucose. IL-3 stimulated glucose uptake in both control and oncogene-transformed cells. With control and ras-transformed cells, enhanced glucose uptake in response to IL-3 was associated with increased affinity of glucose transporters for glucose but with abl-transformed cells, no significant affinity changes were observed. IL-3 also increased glucose transporter expression in both control and oncogene-transformed cells, suggesting that increased transporter expression as well as changes in transporter affinity for glucose can affect glucose uptake.

Animals↗

Nerve tissue-specific human glutamate dehydrogenase that is thermolabile and highly regulated by ADP.

Glutamate dehydrogenase (GDH), an enzyme that is central to the metabolism of glutamate, is present at high levels in the mammalian brain. Studies on human leukocytes and rat brain suggested the presence of two GDH activities differing in thermal stability and allosteric regulation, but molecular biological investigations led to the cloning of two human GDH-specific genes encoding highly homologous polypeptides. The first gene, designated GLUD1, is expressed in all tissues (housekeeping GDH), whereas the second gene, designated GLUD2, is expressed specifically in neural and testicular tissues. In this study, we obtained both GDH isoenzymes in pure form by expressing a GLUD1 cDNA and a GLUD2 cDNA in Sf9 cells and studied their properties. The enzymes generated showed comparable catalytic properties when fully activated by 1 mM ADP. However, in the absence of ADP, the nerve tissue-specific GDH showed only 5% of its maximal activity, compared with approximately 40% showed by the housekeeping enzyme. Low physiological levels of ADP (0.05-0.25 mM) induced a concentration-dependent enhancement of enzyme activity that was proportionally greater for the nerve tissue GDH (by 550-1,300%) than of the housekeeping enzyme (by 120-150%). Magnesium chloride (1-2 mM) inhibited the nonactivated housekeeping GDH (by 45-64%); this inhibition was reversed almost completely by ADP. In contrast, Mg2+ did not affect the nonstimulated nerve tissue-specific GDH, although the cation prevented much of the allosteric activation of the enzyme at low ADP levels (0.05-0.25 mM). Heat-inactivation experiments revealed that the half-life of the housekeeping and nerve tissue-specific GDH was 3.5 and 0.5 h, respectively. Hence, the nerve tissue-specific GDH is relatively thermolabile and has evolved into a highly regulated enzyme. These allosteric properties may be of importance for regulating brain glutamate fluxes in vivo under changing energy demands.

Adenosine Diphosphate↗

Management of penetrating juxtahepatic inferior vena cava injuries under total vascular occlusion.

BACKGROUND: Juxtahepatic inferior vena cava injuries are often lethal. Various operative strategies have been used to improve outcome, but the mortality rate reported in the literature is 80 percent or more. The atriocaval shunt has been advocated for isolation of bleeding retrohepatic vena cava, but recent reports suggest that mortality might be even higher in patients selected for shunting, perhaps owing to ongoing hemorrhage because of indecision and delay prior to insertion, or to technical difficulty with insertion. A series of patients with juxtahepatic inferior vena cava injuries treated successfully with total vascular isolation and occlusion were studied. STUDY DESIGN: Consecutive series of 10 patients with penetrating injuries to the juxtahepatic inferior vena cava were treated at an urban, university-affiliated Level I trauma center. A rapid and direct approach was used along with isolation techniques similar to those used in liver transplantation and elective resection for neoplasm. As resuscitation continued, repair of the inferior vena cava was accomplished in a bloodless field, created by manual compression of the liver, wide exposure, portal inflow occlusion, and proximal and distal control of the inferior vena cava. Aggressive fluid resuscitation and transient aortic cross-clamping controlled resulting systemic hypotension. RESULTS: Mean injury severity score was 26 and mean penetrating abdominal trauma index score was 28. After exposure, three patients had tangential injuries controlled by undersewing a partially occluding clamp. Subdiaphragmatic aortic cross-clamping was performed if total occlusion of the inferior vena cava reduced systolic blood pressure to 60 mm Hg, which was necessary in the remaining seven patients. Nine patients survived surgery, and seven of nine survived to hospital discharge. One postoperative death was a result of multiple organ dysfunction syndrome, and the other of necrotizing bacterial pneumonia. CONCLUSIONS: Total vascular occlusion with selective use of aortic cross-clamping yielded 70 percent survival in an injury that historically has been associated with survival of 20 percent or less. Minimization of visceral ischemia is accomplished by occluding the aorta only after complete isolation of the inferior vena cava.

Adolescent↗

A preliminary investigation of high-school counseling resources on the Cape Peninsula.

In South Africa, counseling and guidance services remain marginalized. The aim of this study was to determine the structure and function of the counseling facilities in high schools on the Cape Peninsula. The first telephone survey comprising 68 representatively and randomly selected schools revealed that 26% of schools had no guidance department, and the mean full-time guidance teacher-pupil ratio was 1:897. The second survey involving 33 randomly selected full-time and part-time guidance teachers from the first sample showed that they could assign on average 14.4 minutes of counselling per pupil in one school year. Analysis of the full-time guidance teachers (N = 22) time allocation revealed that 23% of time was allocated to counseling, 32% to guidance, and 45% to formal teaching and administration. These results suggest that the allocation of personnel and time to counselling are deficient. An implication is that adolescents with psychological problems go undetected and therefore untreated.

Adolescent↗

Etiology and clinical profile of hepatocellular carcinoma in Bangladesh.

Sixty-four consecutive subjects with hepatocellular carcinoma were prospectively studied in the department of Hepatology, IPGMR, Dhaka. Their mean age was 50.11 years. Fifty-two were male and 12 female. Cirrhosis was present in 12 (18.75%) subjects. Thirty subjects (46.88%) had HBsAg in their sera. Seven (58.33% of females) patients gave history of use of oral contraceptives. Cirrhosis, HBV infection, male sex, middle age, and probably the use of oral contraceptives in females appeared to be important risk factors for development of HCC in Bangladesh. Majority of patients presented with upper abdominal pain, weight loss and anorexia. Hepatomegaly was invariably present. Alpha fetoprotein was significantly higher in cirrhotic HCC patients than in non-cirrhotic ones. Median survival was two months. None of the clinical or laboratory features predicted the prognosis.

Adult↗

Peptides derived from C-reactive protein inhibit neutrophil alveolitis.

C-reactive protein (CRP) is the classic acute phase reactant in humans, with serum levels elevated up to 1000-fold after the onset of inflammation. CRP inhibits chemotaxis of complement (C5a)-, LTB4-, IL-8-, and FMLP-stimulated neutrophils in vitro, and rabbits and transgenic mice with elevated serum CRP levels exhibit diminished neutrophil infiltration and vascular permeability in models of chemotactic factor-induced alveolitis. To evaluate the mechanism of CRP inhibition on chemoattractant-induced neutrophil inflammation in vivo, experiments were performed in mice infused with peptides of human CRP shown to inhibit C5a- and FMLP-stimulated neutrophil chemotaxis in vitro. After direct tracheal instillation of FMLP, mice previously injected via the retro-orbital plexus with CRP peptide 77-82 or 201-206 showed significant reductions (up to 90%) of neutrophils in the bronchoalveolar lavage fluid compared with vehicle-treated mice. Both CRP peptides also significantly (up to 55%) inhibited the increase in alveolar total protein levels. Control injections of native rabbit CRP (3 microM) inhibited neutrophil influx by 93% and protein leak by 55% in mice intratracheally instilled with FMLP. Despite similar levels of inhibition, approximately 10-fold more peptide by weight than native CRP was required. These data suggest that CRP degradation products at sites of tissue injury, in particular CRP peptides 77-82 and 201-206, are anti-inflammatory and can diminish lung injury by a reduction in neutrophil influx and protein leakage into alveoli following FMLP-induced inflammation.

Amino Acid Sequence↗

Interaction of reactive nitrogen and oxygen intermediates in HL60 and dimethylsulphoxide-differentiated HL60 cells.

The interaction of reactive nitrogen intermediates (RNI) with reactive oxygen intermediates (ROI) was inferred from the effect of added L-arginine on luminol-dependent chemiluminescence (LCL) and cytochrome C reduction in HL60 cells, dimethylsulphoxide (DMSO)-differentiated HL60 cells and human neutrophils. Phorbol myristate acetate (PMA)-stimulated HL60 cells had no effect on LCL and a decreased rate of cytochrome C reduction in the presence of increasing concentrations of L-arginine. Inhibition of L-arginine-mediated cytochrome C reduction was relieved by L-N(G)-monomethyl arginine (L-NMMA), an inhibitor of nitric oxide synthesis, in a concentration-dependent manner. In contrast, DMSO-differentiated cells and human neutrophils separated from blood showed decreased rates of LCL and cytochrome C reduction with increasing concentrations Of L-arginine, which were relieved to some extent by L-NMMA in a dose-dependent manner. These results are consistent with a 40% increase in the production of nitrate following stimulation of DMSO-differentiated cells and human neutrophils by PMA compared with only a 6% rise in undifferentiated HL60 cells. Possible inhibition of NADPH oxidase has been suggested to explain the responses of LCL, cytochrome C reduction and nitrate production by nitric oxide in the presence of L-arginine.

Catalysis↗