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Biomedical subjects

L Wagner

Publications and source records attributed to L Wagner.

At least 19 recordsLinked to original sources
PubMed1999

[Detection of glycation end products in the urine of diabetic patients].

Advanced glycation end products play an important role in the development of tissue damage in diabetes mellitus. The aim of the present study was the investigation of the excretion of different glycation end products in the urine. Methylglyoxal, an intermediate product of the glycation, formed with L-arginine in an in vitro model two fluorescent peaks. These peaks can be characteristic for imidazolone-like product(s) which are produced also in the reaction of methylglyoxal with proteins described in the literature, suggesting modification of proteins with methylglyoxal at the guanidino group of the L-arginine amino acid. Using the fluorescent characteristics of these (excitation/emission: 320/400 nm and 340/425 nm) and the generally accepted wavelength of the so called non-specific advanced glycation end product (370/440 nm) could be identified these glycation end products in the urine of 98 patients with diabetes mellitus (21 type I., 77 type II., 51 female and 47 male, mean age: 56.6 years). These three particular glycation end products showed significant intercorrelations in the urine (p < 0.001). Concentrations of these glycation end products in the urine correlated negatively with the serum creatinine in the range between 120-240 mumol/l (p < 0.001). Data presented here verify that non-specific glycation end product and imidazolone-like glycation end products can be detected in the urine of diabetic patients. Elimination of these products by the urine is markedly decreased in the stage of early renal insufficiency. These decrease in the secretion can cause an elevation of the advanced glycation end products in the circulation leading progression of diabetic complication.

Diabetes Mellitus, Type 1↗
PubMed1999

[Detection of carbonyl stress markers in the urine of diabetic patients].

Carbonyl stress-induced tissue damage is caused by reactive aldehydes produced by non-enzymatic glycation, oxidative stress and metabolic processes. The aim of this study was the detection of the major markers of carbonyl stress in the urine of diabetic patients (21 type 1, 77 type 2, 51 female, 47 male, 56.6 +/- 13.7 year of age; mean +/- SD). Oxidative stress was detected by using the reaction of malondialdehyde, the end product of free radical damage of the tissues, with L-arginine. This reaction produced a fluorescent compound, pyrimidinyl-L-ornithine. Thus, pyrimidinyl-L-ornithine, as well as pentosidine, an advanced glycation end product, and the non-specific advanced glycation end product, which is thought to be partially as a result of lipid peroxidation, could be detected simultaneously by using the fluorescent method. Correlation coefficients among the concentrations of these products in the urine of 98 diabetic patients were as follows: pyrimidinyl-L-ornithine vs. non-specific advanced glycation end product: r = 0.72, p < 0.001; pentosidine vs. non-specific advanced glycation end product: r = 0.68, p < 0.001; pentosidine vs. pyrimidinyl-L-ornithine: r = 0.60, p < 0.001. Strong negative correlations were found between the serum creatinine levels of these patients, between 120-240 mumol/l, and the urinary concentration of these products: r = -0.88 for non-specific advanced glycation end products, r = -0.86 for pentosidine and r = -0.89 for pyrimidinyl-L-ornithine (p < 0.001 for all three). These data support a closer relation of the so-called non-specific glycation end product to oxidative stress than to non-enzymatic glycation. Results presented here suggest an early retention of the products of carbonyl stress in the patients with moderate renal insufficiency, which can play a role in the development of diabetic complications.

Adult↗
PubMed1999

Sensitivity and specificity of free and total glutaric acid and 3-hydroxyglutaric acid measurements by stable-isotope dilution assays for the diagnosis of glutaric aciduria type I.

Glutaric aciduria type I (GA I) is a recessive disorder caused by a deficiency of glutaryl-CoA dehydrogenase (GCDH). The biochemical hallmark of the disease is the accumulation of glutaric acid and, to a lesser degree, of 3-hydroxyglutaric acid and glutaconic acid in body fluids and tissues. A substantial number of patients show only slightly, intermittently elevated or even normal urinary excretion of glutaric acid, which makes early diagnosis and treatment to prevent the severe neurological sequelae difficult. Furthermore, elevated urinary excretion of glutaric acid can also be found in a number of other disease states, mostly related to mitochondrial dysfunction. Stable-isotope dilution assays were designed for both glutaric acid and 3-hydroxyglutaric acid and their diagnostic sensitivity and specificity were evaluated. Control ranges of glutaric acid in urine were 1.1-9.7 mmol/mol creatinine before and 4.1-32 after hydrolysis. The respective values of 3-hydroxyglutaric acid were 1.4-8.0 and 2.6-11.7 mmol/mol creatnine. For other body fluids, control ranges in mumol/l/L were: for glutaric acid 0.55-2.9 (plasma), 0.18-0.63 (cerebrospinal fluid) and 0.19-0.7 (amniotic fluid); and for 3-hydroxyglutaric acid, 0.2-1.36 (plasma), < 0.2 (cerebrospinal fluid) and 0.22-0.41 (amniotic fluid). Twenty-five patients with GCDH deficiency were studied. Low excretors (12 patients) were defined by a urinary glutaric acid below 100 mmol/mol creatinine down into the normal range, while high excretors (13 patients) had glutaric acid excretions well above this value. With and without hydrolysis there was an overlap of glutaric acid values between patients and controls. Diagnostic sensitivity and specificity of 100% could only be achieved by the quantitative determination of 3-hydroxyglutaric acid with the newly developed stable-isotope dilution assay, allowing an accurate diagnosis of all patients, regardless of the amount of glutaric acid excreted in urine.

Amino Acid Metabolism, Inborn Errors↗
PubMed1999

Inhibitory effect of haptoglobin on granulocyte chemotaxis, phagocytosis and bactericidal activity.

Human haptoglobin (Hp) is synthesized at hepatic and extrahepatic sites as an acute-phase reactant protein (APP). We investigated the effects of Hp on granulocyte function. The chemotaxis of freshly isolated human granulocytes and differentiated HL-60 cells in response to the bacterial tripeptide, f-met-leu-phe, was inhibited in the presence of a physiological concentration of Hp, but chemotaxis in the presence of the proinflammatory cytokine interleukin-8 (IL-8) was not inhibited. Phagocytosis of viable Escherichia coli, as well as fluoresceinated nonviable E. coli, was inhibited. Hp also reduced granulocyte intracellular bactericidal activity against E. coli. The observed inhibitory effects of Hp on granulocyte function are similar to those reported for C-reactive protein and suggest that APPs dampen the acute inflammatory response.

Blood Bactericidal Activity↗
PubMed1998

Preventing discrimination against volunteers in prophylactic HIV vaccine trials: lessons from a phase II trial.

CONTEXT: Preventive HIV vaccines can temporarily cause uninfected individuals to have positive results on HIV testing. As preparations are underway to mount larger efficacy trials, the social risks of trial participation should be studied. OBJECTIVE: To describe frequency of HIV testing and discrimination among participants in a preventive phase II HIV vaccine trial. PARTICIPANTS: 266 vaccine trial volunteers were eligible; 247 participated in a confidential survey. RESULTS: 63 volunteers (26% of respondents) reported 185 HIV tests during the prior 12 to 24 months; most tests were for other research studies, health care, insurance, incarceration, or employment. Only 5 volunteers reported having positive HIV test results. Volunteers reported 99 adverse social incidents or problems, 53 of which were related to the trial. The most common type of event occurred when volunteers disclosed their trial participation and were mistakenly presumed to be infected with HIV. Few reported difficulty obtaining insurance, job loss, and inadvertent disclosure of their participation in the trial. CONCLUSION: In this vaccine trial, few serious social harms were reported. Those who conduct HIV tests for insurance, employment, health care, or other reasons should be made aware that HIV vaccines can cause false-positive HIV test results. Those planning future trials must continue to provide needed support to volunteers. Social harms should be monitored with the same vigilance accorded to physical harms.

AIDS Serodiagnosis↗
PubMed1998

Estimating the prevalence of chronic fatigue syndrome among nurses.

The present study assessed the prevalence of chronic fatigue syndrome (CFS) in a sample of nurses. There is a paucity of studies on the prevalence of CFS in healthcare professionals. Two samples of nurses were recruited through mailed questionnaires. Data were collected on demographic characteristics and symptoms. In addition from the sample, those nurses with CFS-like symptoms were more comprehensively evaluated using a structured clinical interview and reviewing their medical records. A physician review team estimated the prevalence of CFS to be 1,088 per 100,000. These findings suggest that nurses might represent a high-risk group for this illness, possibly due to occupational stressors such as exposure to viruses in the work setting, stressful shift work that is disruptive to biologic rhythms, or to other possible stressors in the work settings (e.g., accidents).

Fatigue Syndrome, Chronic↗
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↗