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Biomedical subjects

K Maier

Publications and source records attributed to K Maier.

At least 19 recordsLinked to original sources
PubMed1992

Ten years experience with therapeutic apheresis in a community hospital.

A retrospective study was carried out on 2,500 therapeutic hemapheresis procedures performed at a community teaching hospital from 1980 to 1990. Seventy-six percent of the procedures consisted of plasmapheresis (PE). The most frequently treated conditions were myasthenia gravis (MG), Guillain-Barré syndrome (GB), hyperviscosity (HV), and thrombotic thrombocytopenia purpura (TTP). Therapeutic results and clinical implications for these four conditions are discussed.

Adult↗
PubMed1992

Local immune components in chronic obstructive pulmonary disease.

Bronchoalveolar lavage (BAL) may have a potential role in contributing to a more precise definition of COPD disorders, but at present little is known about the cellular and biochemical changes that occur in BAL in the different stages of COPD. On the contrary, BAL features due to smoking habits, a well-known risk factor for COPD, have been widely investigated. We submitted to BAL 15 normal nonsmokers, 15 asymptomatic smokers and 11 smokers affected by chronic bronchitis. In this latter group BAL fluid recovery was significantly reduced and cellularity increased, but less prominently than in asymptomatic smokers. The CD4/CD8 ratio was significantly decreased in smokers with and without bronchitis, the CD8 percentage being positively correlated with the smoking history. NK cells were decreased in patients with chronic bronchitis. BAL neutrophils were increased in both smoker groups and a correlation was seen with smoking history and degree of airflow obstruction. Neutrophils are markedly involved in the oxidation of BAL proteins, as we could determine with the evaluation of the methionine sulphoxide/methionine ratio in BAL fluids. This finding may be relevant to better understand COPD pathogenesis and progression.

Adult↗
PubMed1991

Inactivation of enzymes and an enzyme inhibitor by oxidative modification with chlorinated amines and metal-catalyzed oxidation systems.

Oxidative inactivation of various key enzymes and alpha-1-proteinase inhibitor (alpha-1-PI) was studied by treatment with N-chloramines and the metal-catalyzed oxidation (MCO)-systems ascorbate/Fe(III) and ascorbate/Cu(II). Chlorinated amines completely inhibited alpha-1-PI, fructose-1,6-bis phosphatase (Fru-P2ase) and glyceraldehyde phosphate dehydrogenase (GAPD) at a low molar excess, and glucose-6-phosphate dehydrogenase (G6PD) at a high molar excess, but did not impair beta-N-acetylglucosaminidase (beta-NAG), alkaline phosphatase (AP) or lactate dehydrogenase (LDH). MCO-systems affected the activities of Fru-P2ase, GAPD, AP, LDH and G6PD, but not those of beta-NAG or alpha-1-PI. EDTA prevented inactivation of Fru-P2ase, G6PD and LDH by ascorbate/Cu(II) and of Fru-P2ase by ascorbate/Fe(III) suggesting a site-specific oxidation catalyzed by a protein-bound metal ion. In conclusion, N-chloramines and MCO-systems exhibited different properties with regard to oxidative inactivation, sulfhydryl-enzymes were susceptible to both systems, but other enzymes were only susceptible to one or neither system.

Alkaline Phosphatase↗
PubMed1991

Increased levels of oxidized methionine residues in bronchoalveolar lavage fluid proteins from patients with idiopathic pulmonary fibrosis.

Phagocytic cells are believed to play a crucial role in the development of inflammatory lung diseases. We assumed that the oxidation of methionine (met) to methionine sulfoxide [met(O)] by oxygen-derived free radicals released from phagocytes is one parameter to identify the oxidative mechanisms of lung injury. To test this hypothesis we determined the molar ratio of met(O)/met in the soluble protein fraction of bronchoalveolar lavage (BAL) fluids from healthy nonsmokers and from nonsmoking patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis. The met(O)/met ratio of the healthy nonsmoker group (n = 11) was 0.046 +/- 0.008 (mean +/- SEM). In contrast, the met(O)/met ratio of the nonsmoking IPF group (n = 11) was significantly increased to 0.223 +/- 0.053 (p less than 0.0002). The BAL fluids of this group showed strongly increased numbers of neutrophils but normal numbers of alveolar macrophages (AM). In the sarcoidosis group (n = 10) the met(O)/met ratio (0.048 +/- 0.010) was not significantly different from control values. A close relationship was found between the met(O)/met ratios and the relative as well as the absolute neutrophil counts (r = 0.86; p less than 0.0002; n = 22). In contrast, no significant correlation was found between the met(O)/met ratios and the absolute AM counts (r = 0.22; p = 0.32; n = 22). We conclude that mechanisms of oxidative lung injury in IPF can be characterized by oxidation of met and that this oxidation may be mediated by neutrophils.

Adult↗
PubMed1991

Pathogenetic significance of reactive oxygen species in diffuse fibrosing alveolitis.

Excessive release of reactive oxygen metabolites (ROM) from lung inflammatory cells has been claimed to be of major pathogenetic significance in diffuse fibrosing alveolitis. In the present study, the content of oxidized methionine residues [Met(O)] as a percentage of total methionine (Met) in BAL-derived proteins was used to assess the biologic effect of ROM. In addition, procollagen-III-peptide was measured in BAL fluid as a marker of fibroblast activation. We investigated bronchoalveolar lavage (BAL) samples from seven control patients without evidence of interstitial lung disease and from 42 patients with fibrosing alveolitis caused by idiopathic pulmonary fibrosis (IPF), n = 20, or by collagen vascular disease (CVD), n = 22. Met(O) was elevated in the patients with IPF or CVD compared with that in the control subjects (8.86 +/- 1.26 and 8.13 +/- 1.44% versus 3.36 +/- 0.49%, p less than 0.01 and p less than 0.05, respectively; mean +/- SEM). A positive correlation was found between percentage of neutrophils in BAL and Met(O) in both groups separately and combined (IPF, r = 0.84; p less than 0.001; CVD, r = 0.44; p less than 0.05; IPF and CVD, r = 0.60; p less than 0.001), whereas an inverse relationship existed between Met(O) and the percentage of alveolar macrophages in BAL (IPF, r = -0.59; p less than 0.01; CVD, r = -0.24; NS; IPF and CVD, r = -0.41; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Two-dimensional electrophoresis of dog bronchoalveolar lavage fluid proteins.

Proteins of dog bronchoalveolar lavage fluid, obtained by washing the epithelial lining layer of lungs with phosphate-buffered saline, were separated by two-dimensional electrophoresis. Due to the low protein and high salt content of the bronchoalveolar lavage fluid, samples had to be concentrated and desalted. Following electrophoresis the protein spots were visualized by silver staining. Comparing the two-dimensional protein patterns of bronchoalveolar lavage fluid with that from serum, several lung-specific proteins were detected. The most prominent protein, most probably a surfactant-associated protein, showed isoforms with isoelectric points in the range of pH 4.2-4.8, and a molecular mass of 32 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis after reduction with dithiothreitol.

Animals↗
PubMed1990

Genetic and biochemical analysis of glutathione-deficient mutants of Saccharomyces cerevisiae.

Five independently isolated glutathione-deficient (gsh-) mutants of Saccharomyces cerevisae with maximally 6% residual glutathione content have been analysed genetically. Complementation as well as tetrad analysis of the homo- and heterozygous diploids constructed by suitable crosses of the five mutants indicated that all isolates belong to one complementation group and hence represent different alleles of one gene, GSH1. In order to determine the Gsh1 gene product an assay suitable for yeast was developed to determine the activity of gamma-glutamyl-cysteine synthetase catalysing the first step of glutathione biosynthesis. All mutants are severely deficient in gamma-glutamyl-cysteine synthetase (less than 6.5% of the activity of the glutathione competent parental strain) which is in good accordance with the genetic data.

Animals↗
PubMed1990

Clonal analysis of infiltrating T lymphocytes in liver tissue in viral hepatitis A.

The pathogenic mechanism leading to liver tissue injury in hepatitis caused by hepatitis A virus is unclear. We have randomly established T-cell clones from liver biopsies from four patients with hepatitis A. A total of 578 clones was phenotypically analysed. During the acute phase of the disease CD8+ clones dominated over CD4+ clones, whereas in a biopsy taken late after onset of clinical syndromes more CD4+ than CD8+ clones were obtained. Interestingly, in a patient with a second exacerbation of the disease, more than 20% of all clones had the CD3+ WT31- CD4- CD8- 'NK-like' phenotype. All CD8+ clones had cytotoxic activity and approximately 50% of all CD8+ clones showed specific cytotoxicity against autologous fibroblasts infected with hepatitis A virus. The CD8+ cells also produced IFN-gamma in response to these target cells. Variable IFN-gamma production was observed with all types of T-cell clones. These results suggest that the liver injury in hepatitis A is not caused by a viral cytopathogenic effect but is due to an immunopathological reaction of sensitized cytotoxic T lymphocytes against infected hepatocytes. In addition, these studies show an enrichment of CD4-8-T-cell receptor alpha beta-chain-negative T lymphocytes at the site of an inflammation and suggest a role of these cells in an anti-viral reaction.

Acute Disease↗
PubMed1989

Flumazenil disposition and elimination in cirrhosis.

Flumazenil, a new and specific benzodiazepine antagonist that appears to be free of intrinsic pharmacologic action, is extensively metabolized by oxidative processes and represents a high-clearance drug. Consequently, it could be anticipated that hepatic disease affects the elimination and oral bioavailability of flumazenil. Therefore, the pharmacokinetics of flumazenil was evaluated in eight patients who had moderate cirrhosis and in eight age-matched healthy volunteers after a single oral dose (30 mg) and after an intravenous dose (2 mg). The mean half-life (t1/2) was 0.8 versus 1.4 hours (p = 0.003) and total plasma clearance was 1201 versus 705 ml per minute (p = 0.009) for control subjects versus patients with cirrhosis. Bioavailability increased from the normal 28% to 65% (p = 0.001) in patients with hepatic dysfunction. Routine liver tests did not correlate with the elimination of flumazenil in individual patients. It can be concluded that elimination of flumazenil is impaired in patients who have stable alcoholic cirrhosis. Despite the relative wide margin of safety of flumazenil, somewhat lower doses could be effective in such patients if long-term oral use is anticipated.

Administration, Oral↗
PubMed1989

Liver-derived cytotoxic T cells in hepatitis A virus infection.

An autologous in vitro model was developed to analyze the immunologic cause of liver tissue injury during hepatitis A virus (HAV) infection. Human T lymphocytes infiltrating the livers of two patients with acute HAV infection were isolated from liver biopsy cores, cloned, and expanded in vitro. Procedures using a cell culture system with HAV-infected autologous skin fibroblasts demonstrated that 42% and 53% of the liver-infiltrating CD8+ clones were HAV-specific and that they kill HAV-infected skin fibroblasts in a human leukocyte antigen-restricted manner. Data show virus-specific killing by liver-infiltrating T lymphocytes in man and support the hypothesis that liver cell injury in acute HAV infection is mediated by HAV-specific CD8+ T lymphocytes and is not caused by a cytopathic effect of the virus itself.

Adult↗
PubMed1988

[Ulcerative colitis. Activity index for the clinical and histological classification of inflammatory activity].

According to Truelove and Witts, ulcerative colitis has been rated only by clinical classification without taking into account morphological alterations, and so far (in contrast to Crohn's disease) no activity index has been available for clinical studies. Therefore, we have developed an index during a therapeutic trial with mesalazine (5-aminosalicylic acid) to evaluate the initial state of inflammation and assess therapeutic efficacy. The activity index includes 5 items: stool frequency (score 0 to 3), rectal bleeding (score 0 to 3), endoscopy (score 0 to 3), histology (score 0 to 4), and extension of inflammation (score 0 to 4). In 42 patients with ulcerative colitis treatment with mesalazine (2 suppositories of 250 mg 3 times daily) was monitored for 12 weeks. In 37 patients a clinical improvement was observed, as indicated by a significance decrease in the mean activity index from initially 10.2 to 6.1 (after 6 weeks) and 3.4 (after 12 weeks). The proposed index could be modified by additional parameters.

Adult↗
PubMed1988

Human gamma interferon production by cytotoxic T lymphocytes sensitized during hepatitis A virus infection.

The production of interferon (IFN) during a chromium-51 release assay with hepatitis A virus (HAV)-infected fibroblasts and autologous peripheral blood lymphocytes from patients with acute HAV infection was studied to determine whether IFN plays a role in immunopathogenesis of hepatitis A infection in humans. Skin fibroblasts of eight patients after acute HAV infection and from two control persons without history of current or past HAV infection were infected with HAV. Peripheral blood lymphocytes were collected at different times after the onset of icterus and tested in a chromium-51 release assay against autologous HAV-infected skin fibroblasts for their cytolytic and IFN-producing activity. The IFN produced during the assay was characterized and found to have the properties of human gamma IFN. Cytotoxicity and gamma IFN release were virus specific. The cell types responsible for both functions were characterized and found to be in the HLA-dependent T8+ lymphocyte subset. Considering that gamma IFN has an antiviral effect on persistent HAV infection in vitro and that it probably accounts for stimulation of HLA class I antigen expression on hepatocytes, our experimental results presented here demonstrate that human gamma IFN produced by HAV-specific T cells may participate in pathogenesis of hepatitis A infection in humans.

Cells, Cultured↗
PubMed1988

Differentiation of fibroblast stem cells.

Primary human skin fibroblasts derived from the abdomen of 45 female donors of the four age groups 1-20, 20-40, 40-60, and 60-80 years were studied in primary explant, in primary low-density mass cultures, and in primary clonal populations in vitro. As a function of the age of the donor, primary mitotic and postmitotic fibroblasts in the three primary cell systems analysed represent heterogeneous populations with reproducible changes in the proportions of the mitotic fibroblasts MF I, MF II, MF III, and postmitotic fibroblasts PMF IV, PMF V, PMF VI, and PMF VII. These findings make it very likely that equivalent cell types exist in the connective tissue of skin in vivo, and that these cells undergo reproducible changes in the proportions of the mitotic and postmitotic counterparts in vivo as a function of the age of the donor. Secondary mitotic human skin fibroblast populations of the cell line HH-8 in vitro underwent 53.6 +/- 6.0 cumulative population doublings (CPD) in 302 +/- 27 days. If appropriate methods are applied, mitotic fibroblasts differentiate spontaneously into postmitotic fibroblasts which are kept in stationary cultures for up to 305 +/- 41 additional days. As a function of the CPD level and of the duration of stationary culture, secondary mitotic and postmitotic fibroblast populations are heterogeneous populations with reproducible changes in the proportions of mitotic fibroblasts MF I, MF II, and MF III, and postmitotic fibroblasts PMF IV, PMF V, PMF VI, and PMF VII. The seven secondary fibroblast cell types show differentiation-dependent and cell-type specific patterns of [35S]methionine polypeptides in total soluble cytoplasmic and nuclear proteins, in secreted proteins, and in membrane bound proteins. These findings make it very likely that the morphologically recognizable primary and secondary fibroblasts differentiate spontaneously along a seven stage terminal cell lineage MF I - MF II - MF III - PMF IV - PMF V - PMF VI - PMF VII in three compartments of the fibroblasts stem cell system.

Adolescent↗
PubMed1985

[Successful acute treatment of chronic inflammatory intestinal diseases with oral 5-aminosalicylic acid].

The effectiveness of oral 5-aminosalicylic acid (0.5 g t.i.d.) and of salazosulfapyridine (1.0 g t.i.d.) was compared in a randomized controlled study in two groups with 30 patients each with ulcerative colitis and with Crohn's disease. Persistent complaints within the first 5 days were treated with additional methyl-prednisolone (40 mg/d initially). After treatment for 8 weeks patients with ulcerative colitis showed morphologic remissions in 60% of the 5-aminosalicylic acid group and in 53% of the salazosulfapyridine group. Clinical improvement was achieved in 86% in both groups. Clinical improvement in Crohn's disease was seen in 87% of patients of the 5-aminosalicylic acid group and in 80% of the salazosulfapyridine group. This was evidenced by the significant fall (P = 0,0001) of the mean activity index. Additional steroid medication was nearly equal in both treatment groups. There were no side effects during treatment with 5-aminosalicylic acid. In contrast, salazosulfapyridine had to be withdrawn in four patients due to signs of intolerance. 5-Aminosalicylic acid can thus be considered a valuable alternative to conventional treatment on the basis of equal effectiveness as salazosulfapyridine and lack of undesirable side effects.

Adolescent↗