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Biomedical subjects

S Mayer

Publications and source records attributed to S Mayer.

At least 271 records · Page 15Linked to original sources

Relationships between 34 HLA-A, HLA-B and HLA-DR antigens and three serological markers of viral infections in alcoholic cirrhosis.

In order to study the genetic risk of alcoholic cirrhosis, the frequency of 26 HLA-A and -B antigens was compared in 184 normal controls, 175 alcoholic cirrhotic patients and 83 alcoholic patients with hepatic steatosis of carefully selected ethnic origin. Eight HLA-DR antigens were also determined in 95 subjects of the normal control group and 63 patients of the alcoholic cirrhosis group. The incidence of hepatitis B virus antibodies (anti-HBc and anti-HBs) was defined in 74 patients of the alcoholic steatosis group, 170 patients of the alcoholic cirrhosis group and 111 normal controls different from the previously mentioned normal control group. The incidence and the titers of cytomegalovirus and rubella antibodies were also determined in 93 patients of the alcoholic cirrhosis group and the 111 normal controls. Serum immunoglobulin concentrations were measured in the same 93 cirrhotic patients. Compared with the controls, the alcoholic cirrhosis group revealed a significantly higher frequency of HLA-B15 (21.7 vs. 9.8%, p less than 0.00025, corrected p less than 0.050) and HLA-DR4 (38.1 vs. 17.9%, p less than 0.005, corrected p less than 0.050) and a significantly lower frequency of HLA-B13 (2.9 vs. 11.4%, p less than 0.025, corrected p less than 0.050). As for the frequency of all other HLA antigens, there was no significant difference between the three groups (normal controls, alcoholic cirrhosis and alcoholic steatosis).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Low prevalence of intestinal cryptosporidiosis among immunocompetent and immunocompromised patients with and without diarrhoea in southern Germany.

1160 stool specimens, from 160 severely immunocompromised patients, from 70 adults and 180 children with acute diarrhoea and from 60 controls without diarrhoea and without evidence of immunocompromising underlying disorders, were examined for Cryptosporidium excretion. Only two children (1.1%) (one with previous contact to a straying cat and to lambs, the other without known risk) had documented intestinal cryptosporidiosis, whereas none of the symptomatic adults, immunocompromised patients or controls were found to be positive for Cryptosporidium fecal excretion. Other potential protozoal enteric pathogens among immunocompromised patients were only found in seven of 25 patients with HIV infection. We conclude that sporadic intestinal cryptosporidiosis in Southern Germany is a rare disease in humans even of younger age, but should be included in the differential diagnosis of diarrhoea in immunocompetent and immunocompromised patients.

Acquired Immunodeficiency Syndrome↗

Frequencies of glyoxalase I phenotypes as biological markers in chronic alcoholism.

Biological markers for alcoholism would be a valuable tool for early diagnosis. We have studied the phenotype frequencies of genetically determined erythrocyte enzymes in 397 alcoholics, including two populations with liver disease: steatosis (n = 86) and cirrhosis (n = 128) and a population of alcoholics without apparent liver disease (n = 183) compared to a well selected control population (n = 177). Only for Glyoxalase I (GLO) phenotypes (1,2 and 2-1) were significant differences found between the male controls and the male alcoholics. In the total male alcoholic population the frequency of phenotype 1 was significantly increased (23.2% vs. 11%, p less than 0.02), and the frequency of phenotype 2 was significantly decreased (32.3% vs. 46.3 p less than 0.02) compared to the male control population. For normal women the frequency of phenotype 1 and 2 was significantly different from normal men. (1: +177% p less than 0.001, 2: -45% p less than 0.01), but no significant differences were found between alcoholic and normal women. Our results suggest that in male subjects Glyoxalase I phenotype 1 may provide a marker for predisposition to alcoholism.

Alcoholism↗

Assessment of intake from the diet.

Exposure assessment is one of the key parts of the risk assessment process. Only intake of toxicologically significant amounts can lead to adverse health effects even for a relatively toxic substance. In the case of chemicals in foods this is based on three major aspects: (i) how to determine quantitatively the presence of a chemical in individual foods and diets, including its fate during the processes within the food production chain; (ii) how to determine the consumption patterns of the individual foods containing the relevant chemicals; (iii) how to integrate both the likelihood of consumers eating large amounts of the given foods and of the relevant chemical being present in these foods at high levels. The techniques used for the evaluation of these three aspects have been critically reviewed in this paper to determine those areas where the current approaches provide a solid basis for assessments and those areas where improvements are needed or desirable. For those latter areas, options for improvements are being suggested, including, for example, the development of a pan-European food composition database, activities to understand better effects of processing on individual food chemicals, harmonisation of food consumption survey methods with the option of a regular pan-European survey, evaluation of probabilistic models and the development of models to assess exposure to food allergens. In all three areas, the limitations of the approaches currently used lead to uncertainties which can either cause an over- or underestimation of real intakes and thus risks. Given these imprecisions, risk assessors tend to build in additional uncertainty factors to avoid health-relevant underestimates. This is partly done by using screening methods designed to look for "worst case" situations. Such worse case assumptions lead to intake estimates that are higher than reality. These screening methods are used to screen all those chemicals with a safe intake distribution. For chemicals with a potential risk, more information is needed to allow more refined screening or even the most accurate estimation. More information and more refined methods however, require more resources. The ultimate aims are: (1) to obtain appropriate estimations for the presence and quantity of a given chemical in a food and in the diet in general; (2) to assess the consumption patterns for the foods containing these substances, including especially those parts of the population with high consumption and thus potentially high intakes; and (3) to develop and apply tools to predict reliably the likelihood of high end consumption with the presence of high levels of the relevant substances. It has thus been demonstrated that a tiered approach at all three steps can be helpful to optimise the use of the available resources: if relatively crude tools - designed to provide a "worst case" estimate - do not suggest a toxicologically significant exposure (or a relevant deficit of a particular nutrient) it may not be necessary to use more sophisticated tools. These will be needed if initially high intakes are indicated for at least parts of the population. Existing pragmatic approaches are a first crude step to model food chemical intake. It is recommended to extend, refine and validate this approach in the near future. This has to result in a cost-effective exposure assessment system to be used for existing and potential categories of chemicals. This system of knowledge (with information on sensitivities, accuracy, etc.) will guide future data collection.

Animals↗

Hazard identification by methods of animal-based toxicology.

This paper is one of several prepared under the project "Food Safety In Europe: Risk Assessment of Chemicals in Food and Diet" (FOSIE), a European Commission Concerted Action Programme, organised by the International Life Sciences Institute, Europe (ILSI). The aim of the FOSIE project is to review the current state of the science of risk assessment of chemicals in food and diet, by consideration of the four stages of risk assessment, that is, hazard identification, hazard characterisation, exposure assessment and risk characterisation. The contribution of animal-based methods in toxicology to hazard identification of chemicals in food and diet is discussed. The importance of first applying existing technical and chemical knowledge to the design of safety testing programs for food chemicals is emphasised. There is consideration of the presently available and commonly used toxicity testing approaches and methodologies, including acute and repeated dose toxicity, reproductive and developmental toxicity, neurotoxicity, genotoxicity, carcinogenicity, immunotoxicity and food allergy. They are considered from the perspective of whether they are appropriate for assessing food chemicals and whether they are adequate to detect currently known or anticipated hazards from food. Gaps in knowledge and future research needs are identified; research on these could lead to improvements in the methods of hazard identification for food chemicals. The potential impact of some emerging techniques and toxicological issues on hazard identification for food chemicals, such as new measurement techniques, the use of transgenic animals, assessment of hormone balance and the possibilities for conducting studies in which common human diseases have been modelled, is also considered.

Animals↗

Granulocyte progenitor cells (CFU-C) in peripheral blood of normal volunteers following cell collection by continuous flow centrifugation.

During leukapheresis, the donor undergoes cellular depletion which must be compensated. Moreover, the cellular suspensions obtained contain a certain proportion of granulocyte progenitors that form colonies in agar (CFU-C). These findings prompted us to investigate the effect of a donation by cytapheresis on the number of circulating CFU-C present in the donor. Our investigations were carried out on the day the donation was made, and at further fixed dates for a period of six months. Our study covers 25 cases, corticoid premedication was only given to granulocyte donors and not to platelet donors. In the majority of cases, there were no postdonation effects. A few donors had a less stable circulating CFU-C count than is generally considered normal for a healthy subject. In some, quite wide variations were observed but immature cells never appeared in the circulating blood.

Blood Platelets↗

Myocardial contrast agents: recent advances and future directions.

The assessment of perfusion by myocardial contrast echocardiography has evolved from the early contrast agents, including agitated saline solutions and hydrogen peroxide, to the current second-generation contrast agents. Unlike the first-generation contrast agents, which are composed of air, the newer, second-generation agents contain gases with a higher molecular weight and less solubility and diffusivity, improving microbubble persistence. The newer contrast agents are capable of transpulmonary passage and opacification of the left-heart chambers and the myocardial microcirculation after intravenous administration. Also, innovative imaging techniques using harmonics and triggered imaging have minimized tissue signal and improved signal-to-noise ratio, making the assessment of myocardial perfusion possible. Currently, microbubbles are being designed for specific research or clinical use by exploiting certain characteristics of the microbubble such as the shell, surface characteristics, and/or gas content. Some novel applications of microbubble technology include tissue-targeted gene therapy, drug delivery, ultrasound-enhanced thrombolysis, and the assessment of endothelial function and integrity. This review focuses on the composition, physical properties, and acoustic characteristics of the currently available myocardial contrast agents and those under clinical investigation. In addition, the clinical trials involving these agents will also be discussed.

Albumins↗

Influence of recombinant interleukin-2 and alpha- and gamma-interferons on the induction of novel class I antigens.

Previous results obtained in our laboratory showed that novel class I antigens, closely related to HLA-A (TM antigen related to HLA-A9 and GO antigen related to HLA-A24), were expressed on activated HLA-A9 or HLA-A24 peripheral blood lymphocytes (PBL), whatever activation factor was used [mitogenic stimulation (PHA, PWM, Con A), EBV transformation or alloactivation], but not on resting T and B lymphocytes. These antigens were also expressed on HLA-A9 or HLA-A24 common acute lymphoblastic leukaemias (cALL) and some 'immature' chronic lymphocytic leukaemias (B-CLL), but not in hairy cell leukaemias (HCL), most of the B-CLL, acute myeloblastic leukaemias (AML) and acute myelomonoblastic leukaemias (AMoL). In order to investigate the regulation mechanisms of these novel class I antigens, PBL and different leukaemic cell types were treated in vitro with recombinant IL-2 (rIL-2) and alpha and gamma-interferon (rIFN). Our results showed that without previous activation, but after culture with rIL-2, TM and GO antigens could be induced in HLA-A9 or HLA-A24 PBL and enhanced in HLA-A9 or HLA-A24 B-CLL cases, whereas no expression was found in HLA-A9 or HLA-A24 HCL, T-ALL, AML or AMoL. After culture with rINFs, the expression of TM and GO antigens could be induced on HLA-A9 PBL and all HLA-A9 leukaemic cell varieties. Our results support the hypothesis that the expression of class I antigens is induced at an early stage of the cell cycle.

Cell Cycle↗

Precautionary approaches to the appraisal of risk: a case study of a genetically modified crop.

There are strong scientific reasons for holding the broader scope of precautionary approaches to be more consistent with the scientific foundations of rational choice and probability theory than are conventional narrow risk-assessment techniques. The imperatives both of science and precaution can be seen to pull in the same direction. The regulatory appraisal of risk should become more systematic and broader in scope. In particular, a set of criteria can be developed concerning the need for greater humility, completeness, transparency, and participation in regulatory appraisal, with specific attention to the comparison of different options (including mixtures of options), the consideration of benefits and justifications, and the systematic "mapping" of the ways in which different framing assumptions lead to different pictures of performance. A case study of a pilot exercise applying a multi-criteria mapping method to the regulatory appraisal of a genetically modified crop is reported. The results are more complete than orthodox risk assessment, in that they embody consideration of an unlimited array of issues and include consideration of a wide range of different strategic alternatives to the use of GM technologies. It is concluded that conventional regulatory appraisal might be adapted to better address the imperatives of both science and precaution.

Consumer Product Safety↗

[Cold lymphocytotoxins: their relationship with various physiological and pathological conditions].

The significance of cold lymphocytotoxins, observed at 15 degreesC, is not clearly understood at the present time. The frequency of their appearance has been studied in normal subjects (blood donors, aged people, vaccinated subjects, post-traumatic splenectomy) and in patients with a neurologic disease (multiple sclerosis), a neoplasic disease (breast cancer)and hematologic diseases (thrombocytopenia, acute leukemia, chronic lymphatic leukemia, Hodgkin disease and systemic lupus erythematosus). There are no antibodies found in the geriatric group; they are found only in 3,9 % of blood donors and in 18 % of the subjects after vaccinations. A range of 17 to 30 % is found in subjects with breast cancer or multiple sclerosis. More than 50 % of the individuals with Hodgkin disease or lupus erythematosus produce these antibodies (52 % and 73 % respectively). In acute leukemias and chronic lymphatic leukemias, lymphocytotoxic antibodies sometimes appear at 37 degrees, reacting with autologous cells and having no HL-A specificity.

Acute Disease↗

Nicotine exposure reduces N-methyl-D-aspartate toxicity in the hippocampus: relation to distribution of the alpha7 nicotinic acetylcholine receptor subunit.

BACKGROUND: Exposure to nicotine has been shown to promote neuronal survival after excitotoxic insult to the brain. The role of specific nicotinic acetylcholine receptors (nAChRs) subtypes in mediating this effect is not well understood, however. Examination of distinct receptor subtypes in promoting neuronal survival is of importance not only in understanding the regulation of necrotic cell death but potentially in the development of novel pharmacological therapies that may reduce this form of neurodegeneration. MATERIAL AND METHODS: The present studies examined the relationship between distribution of alpha7 subunit-bearing nAChRs, using autoradiographic imaging of [125I]alpha-bungarotoxin binding, and protective effects of nicotine against excitotoxic damage. Organotypic cultures of rat hippocampus were exposed to N-methyl-D-aspartate (NMDA; 200 microM) for 1 hour with or without (-)-nicotine (0.1-10 microM) and the alpha7 nAChR antagonist methyllycaconitine (MLA; 100 nM). Neuronal damage was assayed 24 hours later by observation of uptake of the non-vital fluorescent marker propidium iodide. RESULTS: NMDA exposure produced significant neurotoxicity, particularly in pyramidal cell layers of CA3 and CA1, that was prevented by co-exposure to MK-801 (10 microM). Localization of the alpha7 subunit was varied with no binding observed in the dentate gyrus, low density in the CA3 and CA1 regions, and dense binding in the hilus. In all regions, co-exposure to (-)-nicotine (0.1-10.0 microM) significantly reduced (>30%) the cytotoxic consequences of NMDA insult. This protective effect was inhibited by co-exposure to MLA in the dentate and CA3, and to a lesser extent, CA1 regions. CONCLUSIONS: The neuroprotective effect of nicotine against excitotoxicity, then, is not directly related to alpha7 subunit localization in the hippocampus.

Animals↗

Selling off the genome?

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Biological Specimen Banks↗

[Chediak-Higashi syndrome. Study of lymphocyte transformation stimulated by phytohemaglutinin (PHA)].

The reactivity to PHA stimulation of peripheral blood lymphocytes from a child with a Chediak-Higashi syndrome was studied. Lymphocyte transformation was assayed by tritiated-thymidine incorporation. Patient lymphocytes reacted to much lower concentrations of PHA than normal controls. With an optimal dose of PHA the peak of thymidine uptake occurred on day 2 of incubation instead of day 4 as observed in normals.

Chediak-Higashi Syndrome↗

[A new case of hemoglobin G Georgia (author's transl)].

A new case of hemoglobin G Georgia (alpha95 Pro yields Leu) is described in a portuguese patient with lymph node tuberculosis. The patient had a slight anaemia with haemolytic crises and moderate splenomegaly. The electrophoretic mobility of this unstable, abnormal haemoglobin was slower than that of Hb S. The percentage of the major (alpha2 G beta2) and the minor (alpha2 G delta2) abnormal components was determined by DEAE-sephadex chromatography and was 18% and 1% respectively. Structural analysis showed the replacement of a proline residue in position 95 (G) in the alpha chain by a leucine residue. This residue alpha 95 interferes with the alpha 1-bêta 2 contact. Functional studies have shown an increased oxygen affinity, a reduced hem-hem interaction and a normal Bohr effect.

Anemia, Hemolytic↗

[Comparative study of a factor-VIII inhibitor in a non-hemophylic patient and in a patient with hemophylia A gravis].

In this study, we tried to make a comparison between the findings concerning two human strong anti Factor VIII inhibitors. In one case, the strong inhibitor appeared in an old man without any particular antecedant. In the second case, it occurred in a young hemophiliac A. We found in both cases that the inhibitor was a immunoglobulin G with light chain lambda. Its activity site is on the fragment AB. These anticoagulants have a inhibitory action against only the Factor VIII procoagulant fraction and have exclusively neutralising properties. The inhibitor present in the non hemophiliac patient has particularly great resistance to temperature and pH variations.

Adult↗

[Hodgkin's disease. T lymphocyte defect in patients in complete remission (author's transl)].

11 patients with Hodgkin's disease in remission, including 7 patients with an initial stage III-IV, off treatment for at least 6 months, were tested for blood T lymphocyte functions. All were completely re-evaluated at the end of treatment to assess complete remission. The number of peripheral blood lymphocytes was below 1,200/cu mm 5/11 patients. Absolute numbers of E-rosette-forming T lymphocytes were decreased in 8 patients, whereas active rosettes were normal in 4/6. A slightly increased percentage of EAC rosettes, a marker for B lymphocytes, was found in only 2 patients. In vitro lymphocyte reactivity to a sub-optimal dose of PHA was studied in 9 patients. A statistically significant defect of lymphocyte transformation was observed in the patient group T lymphocytes. A membrane change is suggested rather than a true depletion. The persistance of such abnormalities long after treatment may raise the question of a complementary immunostimulating treatment in these patients.

Adolescent↗