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Biomedical subjects

L Wagner

Publications and source records attributed to L Wagner.

At least 91 records · Page 5Linked to original sources
PubMed1998

Beta-chemokines are released from HIV-1-specific cytolytic T-cell granules complexed to proteoglycans.

CD8+ lymphocytes are believed to be important in host defence against the human immunodeficiency virus (HIV)-1, inhibiting HIV-1 replication through both cytolytic and non-cytolytic pathways. The cytolytic pathway involves calcium-dependent exocytosis of perforin and granzyme proteases, as well as Fas-mediated programmed cell death, whereas the noncytolytic pathway involves the release of chemokines that prevent viral entry. Using granzyme A as a marker of cytolytic granule proteins, and macrophage inflammatory protein (MIP)-1alpha and RANTES as markers of HIV-1 inhibitory chemokines, we show that these two very different mediators of viral inhibition are both localized in the cytolytic granules of HIV-1-specific CD8+ cytotoxic T lymphocytes (CTL). Following antigen-specific activation, these mediators are secreted together, facilitating both lysis of virion-producing cells and the inhibition of free virus. In addition, RANTES, MIP-1alpha and MIP-1beta are secreted by CTL as a macromolecular complex containing sulphated proteoglycans. This association appears to have a functional significance, because heparan sulphate facilitates RANTES inhibition of HIV-1 infection of monocytes.

Cell Line, Transformed↗
PubMed1998

In search of the abominable consent form: the impact of readability and personalization.

This study assessed the impact of readability and personalization of informed consent forms on initial impressions of therapists and on recall of the information provided on the forms. Eighty-five participants received consent forms that varied in terms of readability and personalization, and were asked to rate their impressions of the therapist. More readable forms increased participants' impressions of the therapist's expertness and the form's helpfulness. Personalized forms increased ratings of the attractiveness of the therapist, and of the relevance of-and satisfaction with-the forms. Personalized forms also tended to increase recall. These properties of consent forms may indeed influence how clients initially react to therapists.

Adolescent↗
PubMed1998

Isradipine prevents global and regional cocaine-induced changes in brain blood flow: a preliminary study.

The L-type calcium channel antagonist, isradipine, reduces brain ischemia in animal models of ischemic stroke. These effects of isradipine appear more pronounced in dopamine (DA) rich brain regions. These same DA-rich brain regions have also been shown to be the areas most affected by cocaine-induced ischemic changes. Using a novel quantified approach to single photon emission computerized tomography, we demonstrated that isradipine pre-treatment prevented cocaine-induced ischemic changes, especially in these DA-rich brain regions. This is the first demonstration that any medication, including isradipine, can prevent the ischemic effects of cocaine on brain blood flow. Isradipine may, therefore, be a useful therapeutic agent for the prevention of brain ischemia in cocaine addicts.

Adult↗
PubMed1998

Demonstration of dose-dependent global and regional cocaine-induced reductions in brain blood flow using a novel approach to quantitative single photon emission computerized tomography.

Ischemic stroke is a common cause of morbidity and mortality in cocaine addicts. Because the previous semiquantitative single photon emission computerized tomography (SPECT) method for measuring brain blood flow does not quantify blood flow, the magnitude and specificity of cocaine's effects during drug taking has not been well established. Here, using a novel quantitative approach to SPECT, we established that intravenous cocaine administration to nine recently abstinent cocaine-dependent subjects was associated with significant decreases in global and regional brain blood flow to dopamine-rich areas such as the prefrontal, frontal temporal, and subcortical gray matter. Establishing the utility of this relatively new quantitative SPECT technique provides an important tool for the management of vascular disorders of the brain. Additionally, identifying the site-specific effects of cocaine provides targets for the development of putative therapeutic medications to attenuate or minimize ischemic stroke in cocaine addicts.

Adolescent↗
PubMed1998

Culture of human insulinoma cells: development of a neuroendocrine tumor cell- and human pancreatic islet cell-specific monoclonal antibody.

We report on the culture of human insulinoma cells derived from a 32-year-old male patient with hyperinsulinism due to an insulinoma of the pancreas. A single-cell suspension was made by passing insulinoma fragments through a fine-gauge stainless-steel mesh. Cluster-forming insulinoma cells resembling pancreatic islets grew in the presence of fibroblasts. The insulinoma cell clusters could be differentiated from fibroblasts by using in situ pan optic staining and specific immunocytochemical staining (anti-human insulin and anti-human insulinoma monoclonal antibody (mAb) D24). mAb D24 was generated using insulinoma cells as antigen for immunization of a Balb/C mouse and cell fusion by the hybridoma cell technique. The anti-insulinoma cell mAb recognized a 32 kDa protein on immunoblot analysis of neuroendocrine tumor cells. D24 mAb also reacted immunohistochemically with normal pancreatic beta-cells and tumors such as vipoma, gastrinoma and carcinoid. Insulinoma cell clusters separated from fibroblasts by micromanipulation and plated into multiwell culture dishes exhibited an insulin-secretion rate of approximately 30 U/100 cells per 24 h with no insulin-secretory response to elevated glucose concentration. Purified insulinoma cells incubated with 1 ng/ml human nerve growth factor expressed neurofilament and neurite extension. These findings together with earlier observations in animal models suggest that human pancreatic beta-cells share some properties with neurons and are related to other neuroendocrine cells in the gastrointestinal tract.

Adult↗
PubMed1998

Hypertension in African-American males.

Hypertension is more prevalent in African-Americans than in Caucasians, and African-Americans experience more rapid progression of end-organ damage from this often "silent" disease than do whites. African-American males are particularly at risk because they often are unaware of the disease, do not receive treatment, and/or do not adhere to a treatment regimen if one is prescribed. Management of hypertension in African-American men is complex and requires consideration of the unique aspects of this special-need population. This article outlines some of the special concerns related to hypertension management in African-American men, including differences in pathophysiology, lifestyle, education, and socioeconomic status. Advanced practice nurses, with their additional knowledge and their strong emphasis on patient education and holistic care, possess the skills to competently, caringly, and creatively manage hypertension with African-American clients.

Adult↗
PubMed1997

Possible role of free radicals generated by pseudohypoxia in the regulation of hepatic glucose output. An in vitro model using rat liver microsomal glucose 6-phosphatase.

Hepatic glucose output is decreased by hyperglycaemia through an unknown mechanism. We hypothesize that free radicals generated by hyperglycaemic pseudohypoxia might cause glucose output to decrease by inhibiting glucose 6-phosphatase - a key enzyme of gluconeogenesis. To prove this a model experiment was performed on a microsome fraction of rat liver. One of the characteristic features of pseudohypoxia due to hyperglycaemia is an increase in the ratio of NADH/NAD+, so in the present study the changes in NADH - induced glucose 6-phosphatase activity were investigated as related to the release of inorganic phosphate (Pi) derived from glucose 6-phosphate. After incubation for 50 min, Pi release was significantly reduced by NADH (4.026 +/- 0.189 vs 2.696 +/- 0.429 micromol x l(-1) x mg protein(-1), control vs NADH samples, p < 0.01). The decrease in the activity of glucose 6-phosphatase generated by NADH was prevented by using desferrioxamine, an irreversible ferric chelator, butylated hydroxytoluene and Trolox, two agents which inhibit lipid peroxidation, and reduced glutathione, a non-specific radical scavenger. Superoxide dismutase, catalase and the hydroxyl radical scavenger dimethyl sulphoxide proved to be ineffective. When the above investigations were carried out in the presence of a ferric-EDTA complex the inhibition of glucose 6-phosphatase was found to be inducible by hydrogen peroxide and/or hydroxyl free radicals. These investigations seem to indicate that pseudohypoxia due to hyperglycaemia can inhibit the activity of glucose 6-phosphatase both by lipid peroxidation and by inducing hydrogen peroxide and/or hydroxyl free radicals and thus it may play a part in the glucose-induced decrease of hepatic glucose output.

Adenosine Triphosphate↗
PubMed1997

Dihydropyrimidinase deficiency and congenital microvillous atrophy: coincidence or genetic relation?

We describe a boy of consanguineous parents who suffered from intractable diarrhoea due to congenital microvillous atrophy, a recessively inherited autosomal disorder. He developed severe cholestatis starting at 2 weeks of age and leading to liver cirrhosis. His psychomotor development appeared only slightly delayed. At the age of 7 months he died due to septicaemia. In addition to disturbances of electrolyte balance and renal tubular function, which could be attributed to microvillous atrophy, marked elevations of dihydrouracil and dihydrothymine as well as moderately elevated excretion of uracil and thymine in urine were repeatedly demonstrated, suggesting a disorder of pyrimidine degradation. An enzymatic defect of 5,6-dihydropyrimidine amidohydrolase (EC 3.5.2.2, dihydropyrimidinase, DHP) was demonstrated in liver biopsy. As both of these recessive disorders seem to be extremely rare, it remains speculative, whether he suffered from two independently inherited metabolic diseases or whether this represents a hitherto undescribed contiguous gene syndrome.

Amidohydrolases↗
PubMed1997

Politics, science, and the emergence of a new disease. The case of chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) emerged as a diagnostic category during the last decade. Initial research suggested that CFS was a relatively rare disorder with a high level of psychiatric comorbidity. Many physicians minimized the seriousness of this disorder and also interpreted the syndrome as being equivalent to a psychiatric disorder. These attitudes had negative consequences for the treatment of CFS. By the mid-1990s, findings from more representative epidemiological studies indicated considerably higher CFS prevalence rates. However, the use of the revised CFS case definition might have produced heterogeneous patient groups, possibly including some patients with pure psychiatric disorders. Social scientists have the expertise to more precisely define this syndrome and to develop appropriate and sensitive research strategies for understanding this disease.

Attitude of Health Personnel↗
PubMed1997

Expression of the Zn finger gene, EVI-1, in acute promyelocytic leukemia.

The EVI-1 gene encodes a Zn finger, DNA binding protein previously detected in some acute myelogenous leukemias (AML) and myelodysplasias (MDS), but not in normal marrow or cord blood cells. Experimental studies suggest EVI-1 blocks cellular differentiation by binding to GATA-1 or other specific DNA sequences controlling gene expression, and may be involved in the pathogenesis of some AMLs. To further define potential roles for EVI-1 in leukemia pathogenesis, we studied its regulation in acute promyelocytic leukemias (APL). Seven of 11 APL cases expressed EVI-1 RNA detected by RNA PCR at diagnosis, and expression was detected in two additional cases after treatment with all-trans retinoic acid (ATRA). Two of four cases studied at relapse also expressed EVI-1 RNA. To investigate regulation of EVI-1 expression in APL, we examined its expression in the NB4 APL cell line. NB4 cells did not express EVI-1 under basal conditions, but expressed EVI-1 after ATRA-induced differentiation. When NB4 cells were exposed to ATRA and transferred to cultures with N,N'-hexamethylene-bis-acetamide (HMBA), differentiation occurred but EVI-1 RNA was not detected, indicating that EVI-1 expression was not required for terminal, NB4 differentiation. ATRA-resistant NB4 cells were obtained by continuous culture in gradually increasing concentrations of ATRA. These cells did not express markers of differentiation but continued to express EVI-1 for several weeks even after ATRA withdrawal. To assess whether expression of the APL PML-RAR alpha fusion gene alone was sufficient for ATRA induction of EVI-1, the PML-RAR alpha gene cDNA was expressed in U937 histiocytic lymphoma cells. ATRA treatment of PML-RAR alpha-transfected or control U937 cells did not induce EVI-1 expression. In conclusion, this study demonstrates the EVI-1 gene is consistently expressed in APL cells either constitutively or after ATRA treatment. ATRA represents the first biologically active agent shown to specifically regulate EVI-1 expression in blood cells. In contrast to previous studies in AML and MDS, the pattern of EVI-1 expression suggests it may facilitate rather than inhibit myeloid differentiation during ATRA treatment. However, effects of EVI-1 expression are likely to be complex, and expression in ATRA-resistant APL cells may indicate multiple roles for this gene.

Acetamides↗