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Biomedical subjects

T Müller

Publications and source records attributed to T Müller.

At least 415 records · Page 23Linked to original sources

Cholinergic-adrenergic balance: Part 2. Relationship between drug sensitivity and personality.

Sensitivity to the centrally active cholinomimetic physostigmine varies dramatically among healthy individuals. The elucidation of the reasons for this variability could contribute to the understanding of the pathophysiology of affective disorders where a cholinergic supersensitivity has been demonstrated. Therefore, personality characteristics and habitual stress-coping strategies were related to sensitivity to physostigmine in eight healthy male volunteers. Cardiovascular and behavioral responses tended to be positively correlated with irritability and emotional liability. Passive, "helpless" strategies for coping with stress were positively related to these responses. The metabolic and neuroendocrine responses to physostigmine were generally unrelated to personality. In view of putative beta-adrenergic disturbances in depression, the responses to the peripheral beta 2-adrenergic agonist reproterol were studied. Irritability and emotionality tended to be positively correlated with cardiovascular responses to reproterol as well as with reductions of heart rate by the peripheral cholinomimetic neostigmine.

Adult↗

Latent inhibition of granulocyte function by cyclosporine A.

According to the literature, Cyclosporine A (CsA) is said to suppress specifically the activity of T and B cells. A significant influence on phagocyte function has been neglected. However, aggravated courses of bacterial and fungal infections have been frequently reported under the treatment with CsA, suggesting that a latent depression of phagocytic activity may possibly occur under clinical circumstances. Therefore, this study set out to assess whether CsA can also change granulocyte function under therapy conditions or not. Thirty-seven patients, 3 months-10 years after kidney transplantation being under immunosuppressive treatment with CsA + Prednisolone (n = 25), Azathioprine + Prednisolone (n = 6) and under Prednisolone alone (n = 6) underwent the study. 18 healthy persons served as a normal control group. Granulocyte function was tested ex vivo by chemiluminescence (CL) after stimulation with phorbolmyristate acetate (PMA) and with zymosan (zym) activated autologous or pool-serum. The obtained data were correlated to corresponding serum or plasma levels of CsA, human leukocyte elastase (HLE) and neopterin. Comparing the three therapy groups with the healthy control and with each other no differences could be seen in median CL values; but there was a significant (p = 0.05) negative correlation between CsA blood levels and maximum CL values of PMN. Such inhibition of CL could be calculated for zym but not for PMA stimulated PMN; suggesting that the CsA mediated inhibition of granulocyte function may be only partial and restricted to phagocytosis. In addition, a positive correlation between serum levels of human leukocyte elastase (HLE) and neopterin could be found. This indicates a simultaneous influence of CsA on both PMN and macrophages.

Adult↗

Kinetics of pulmonary leukocyte sequestration in man during hemodialysis with different membrane-types.

Although it has been suggested that pulmonary sequestration of leukocytes could account for membrane-dependent white blood cell depletion in HD, direct evidence in patients is still lacking. Therefore a study was initiated to test whether and how leukocytes distribute in the lung circulation during HD with different membranes. Thirteen patients suffering from chronic renal failure underwent lung scintigraphy during HD with cuprophane (n = 3), hemophane (n = 8) and polysulfone (n = 2) lowflux capillary dialyzers. Isolated autologous leukocytes were labelled with 99m-Technetium and reinfused before starting HD. Distribution of leukocyte related activity was registered by lung scintigraphy. In comparison to normal lung scintigraphy performed without HD, an impressive redistribution peak was demonstrated 10-20 min after the start of HD with cuprophane and also to a lesser extent with hemophane. When HD was performed with polysulfone the decrease in activity was delayed but no real redistribution was obtained. In accordance with other phenomena, such as peripheral leukopenia and changes in granulocyte oxidative metabolism, pulmonary sequestration of leukocytes takes place in man in the initial phase of HD and appears to be strongly dependent on the type of membrane.

Humans↗

[Changes in the plasma protein concentration as a factor influencing the fructosamine value].

Fructosamine values are notably influenced by plasma protein concentration. Total protein concentration in addition to variations in the plasma protein concentrations (Dysproteinemia) play a role here. This is a result of the various glycosylation of the different plasma proteins. Since fructosamine behaves similar to total protein for hypo- and hyperproteinemia, a good relationship with the total protein is expected for normoproteinemia. Hence, no erroneous high nor low fructosamine values are obtained. Dysproteinemia at normal total protein concentration causes no erroneous fructosamine values with the exception of some illnesses. Therefore, a direct relationship between protein and fructosamine at normoproteinemia is not generally necessary.

Blood Proteins↗

A rapid laser immunonephelometric assay for serum amyloid A (SAA) and its application to the diagnosis of kidney allograft rejection.

We set up a laser nephelometric assay for the quantitation of serum amyloid A (SAA) in human plasma. Therefore monospecific antibodies were raised in sheep and used in parallel to measure SAA concentrations by nephelometry and also by radial immunodiffusion, an assay usually applied for determination of SAA. The nephelometric method is precise, simple and unlike radial immunodiffusion results are obtained within an hour. The antigen concentrations determined both by laser nephelometry and radial immunodiffusion correlated highly (r = 0.98). As plasma SAA concentrations were reported to be a possible marker of kidney allograft rejection, the assay was applied to measure SAA concentrations in patients after kidney transplantation. Data were compared with clinical and other biochemical parameters. The period after kidney transplantation is reported for two cases, where SAA plasma concentrations were helpful in diagnosing allograft rejection. The rapid availability of the SAA plasma concentrations by nephelometry makes them a possible additional tool to decide quickly upon antirejection therapy.

Graft Rejection↗

Reversible and irreversible rotating field-induced membrane modifications.

We analyse the charge distribution as submitted by additionally induced transmembrane potentials in rotating electric fields. In contrast to d.c. and a.c. fields, in rotating fields the induced peak potential differences across the membrane systems are phase shifted with respect both to each other and to the external field vector. These phase differences are strongly frequency-dependent but were also influenced by the electrical properties of both the cell and the surrounding medium. We extend our investigation up to the non-linear field strength range of electrorotation and found reversible and irreversible changes in the rotational behavior of several cells. The most convenient variables for describing non-linear electrorotation are the characteristic frequency (fc1) and the corresponding angular velocity (omega c) of the cells. With increasing field strength the observed rotational behavior becomes more and more irreversible and finally rupture of the membrane occurs.

Animals↗

The lipoxygenase pathway and chemiluminescence in horse eosinophilic leukocytes.

It was shown in several cell types that the dual lipoxygenase and cyclooxygenase inhibitor eicosatetraynoic acid but not the cyclooxygenase inhibitor acetylsalicylic acid suppressed luminol-dependent chemiluminescence. Since lipoxygenase is known to generate chemiluminescence in vitro, these observations were interpreted as evidence for a direct contribution of the lipoxygenase pathway to light emission in intact cells. We have investigated a possible contribution of the lipoxygenase to the chemiluminescence of horse eosinophils by directly comparing the formation of the byproduct chemiluminescence with the formation of stable end-products of the lipoxygenase pathway, leukotrienes and HETEs. Azide as well as eicosatetraynoic acid almost completely inhibited chemiluminescence stimulated by the calcium ionophore A23187 but had less effect on the formation of leukotrienes. The tumour-promoting ester, phorbol myristate acetate, stimulated chemiluminescence in an azide- and eicosatetraynoic acid-sensitive manner and failed to evoke the production of leukotrienes. Azide, but also eicosatetraynoic acid inhibited the luminol-dependent chemiluminescence generated by isolated eosinophil peroxidase in the presence of H2O2. Our results argue against a direct role of the lipoxygenase pathway in the generation of light in horse eosinophilic leukocytes but do not exclude that product(s) of this pathway may be involved in stimulus-response coupling.

Animals↗

A mammary-derived growth inhibitor (MDGI) related 70 kDa antigen identified in nuclei of mammary epithelial cells.

The aim of the present study was to investigate the expression of the mammary-derived growth inhibitor (MDGI) and the subcellular localization of MDGI-related antigens in bovine mammary glands. Cell-free translation of poly(A+) = RNA, immunoprecipitation with rabbit anti-MDGI-antibodies, and estimation of the relative contents of MDGI by a radioimmunoassay in mammary tissue of different functional states revealed that the 13 kDa MDGI was dramatically increased in terminally differentiated mammary tissue compared with the proliferating tissue from pregnant animals. To address the question of tissue localization, polyclonal anti-MDGI antibodies and antibodies directed against a synthetic peptide corresponding to residues 69 to 78 of MDGI were used. Western blotting of tissue fractions revealed the cytosolic and microsomal localization of MDGI. Additionally, both types of antibodies detected a 70-kDa antigen in the nuclear fraction of differentiated mammary glands. Salt extraction and DNase I digestion of isolated nuclei, as well as chromatin purification, indicated an association of the 70-kDa antigen with the chromatin. By means of the immunogold technique, MDGI-related antigens were localized within euchromatic nuclear regions of epithelial cells in the intact differentiated mammary gland. The immunostaining was markedly diminished in the proliferating tissue. This finding raises the possibility that MDGI and the 70-kDa antigen influence cell proliferation by acting on gene expression within the nuclei of mammary glands.

Animals↗

DNA-DNA dot hybridization technique used as DNA determination method in the alkaline elution analysis of DNA damage.

A DNA-DNA ('Southern') dot hybridization technique was adapted for use as a quantitative DNA detection method during alkaline elution analysis of irradiated rat cell material. In comparison to standard microfluorometric methods, similar gamma-ray dose-response relationships were obtained with less than 1% of the cell material when the dot hybridization assay was used. When a highly repetitive, long interspersed DNA element of the rat genome is used as a hybridization probe, as few as 10(4) cells of rat tissue or rat cell culture cells per sample with approx. 50 ng of DNA were sufficient to detect single-strand breaks and protein cross-links in the DNA of rat hepatocytes and cells of the nasal epithelium after in vitro gamma-irradiation. Since highly repetitive DNA elements are available from nearly all higher eukaryotes, this alternative approach of detecting DNA in alkaline elution analysis is generally proposed for tissues which yield only low amounts of cell material and/or which are difficult to label by radioactive DNA precursors.

Animals↗

Effects of clonidine and dihydralazine on atrial natriuretic factor and cGMP in humans.

The effects of a 1-wk treatment with clonidine (75 micrograms/day twice a day) and dihydralazine (25 mg/day twice a day) on base-line levels of plasma atrial natriuretic factor (ANF) and plasma and urinary guanosine 3',5'-cyclic monophosphate (cGMP) and their changes by acute saline infusion (2 liters) in eight normal subjects were evaluated. Basal ANF was decreased to 65% in the clonidine group compared with both the control and dihydralazine groups. Volume loading increased plasma ANF levels by 30-40% of base-line values in the control and the dihydralazine groups and by 15% in the clonidine group. Basal plasma and urinary cGMP levels were raised by 30 and 90% in the dihydralazine group compared with both other groups. Volume loading increased plasma cGMP levels by 40% in the control and clonidine-treated groups and by 25% in the dihydralazine-treated group. It is concluded that ANF may contribute to hemodynamic effects of clonidine but not to those of dihydralazine. Dihydralazine increases plasma and urinary cGMP, supposedly by direct activation of the soluble guanylate cyclase.

Adult↗