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Biomedical subjects

B Möller

Publications and source records attributed to B Möller.

At least 19 recordsLinked to original sources

Soluble tumor necrosis factor (TNF) receptors conserve TNF bioactivity in meningitis patient spinal fluid.

The content of tumor necrosis factor (TNF)-alpha antigen and the bioactivity of soluble TNF receptor type II (sTNF-RII) in cerebrospinal fluid (CSF) from 29 patients with meningeal symptoms and fever were examined. Immunoreactive TNF was demonstrated in CSF from 4 of 7 patients with bacterial meningitis. In 3 of 8 patients with aseptic meningitis, CSF also contained TNF, but TNF bioactivity was confined to samples from patients with bacterial meningitis. Bioactive TNF was exclusively in high-performance liquid chromatography fractions containing 30- to 60-kDa proteins. Lipopolysaccharide induced down-regulation, possibly after shedding of granulocyte surface membrane TNF-RII. Consistently, there was a statistically significant correlation between sTNF-RII and CSF leukocyte counts. Bioactive TNF was found only in CSF containing >1 ng of sTNF-RII/mL; samples without TNF bioactivity contained less sTNF-RII. Thus, a stabilizing effect of sTNF-RII on the oligomeric cytokine in vivo is plausible.

Cells, Cultured

A simple method for preoperative assessment of the best fitting electrode length in single lead VDD pacing.

For single lead VDD pacing, electrodes with various distances between the lead tip and the floating atrial dipole (AV distance) are available. Using different AV distances allows positioning of the atrial dipole in the mid- to high right atrium, regardless of the size of the right heart. In this position, reliable atrial sensing and rejection of ventricular far-field potentials can be expected. A simple test for the preoperative assessment of the best fitting AV distance in the individual patient was tested. We studied 24 consecutive patients prior to implantation of a VDD pacemaker. With the patient in supine position, a test electrode with an AV distance of 13 cm was taped onto the thorax. Under fluoroscopic control, it was moved until its course and projection onto the heart was equal to that of a ventricular lead. If fluoroscopy then showed a projection of the atrial dipole onto the mid- to high right atrium, a lead with a similar AV distance of 13 or 13.5 cm was used for implantation. If the atrial dipole projected itself too high or too low, a shorter or longer lead had to be implanted. The maximum time for the test was 2 minutes, and the maximum fluoroscopy time was 15 seconds. According to the test, a lead with an AV distance of 13 or 13.5 cm was implanted in 18 of 24 patients, and a lead with an AV distance of 15.5 or 16 cm was implanted in 6 of 24 patients. The atrial dipole could easily be positioned in the mid- to high right atrium in all patients, demonstrating a correct preoperative assessment of the best fitting AV distance. Intraoperatively, a P wave amplitude of 3.5 +/- 3.0 mV was measured. The described test allows a fast and reliable assessment of the best fitting electrode length in single lead VDD pacing.

Adult

Sodium and dopamine excretion in prehypertensive Dahl rats during severe hypervolaemia.

As opposed to the salt-resistant Dahl-R rat the salt-sensitive Dahl-S has a defective renal dopamine DA1 receptor that may be involved in its susceptibility to develop hypertension during a high salt diet. To compare the ability of prehypertensive Dahl-R and Dahl-S to respond to a severe isotonic sodium load, renal function was monitored during a severe form of acute isotonic volume expansion (10% VE). Mean arterial blood pressure before VE was similar in Dahl-R and Dahl-S and decreased in both strains by 6% during VE. The accumulated sodium excretion during VE in Dahl-R was 411 +/- 64 micromol 100 min(-1) g(-1) kidney wt (kw) which was not different from that in Dahl-S (420 +/- 95 micromol 100 min(-1) g(-1) kw). The accumulated dopamine excretion (a mirror of renal dopamine synthesis) during VE was also similar in Dahl-R (134 +/- 13 ng 100 min(-1) g(-1) kw) and Dahl-S (126 +/- 16 ng 100 min(-1) g(-1) kw). The excretion of DOPAC, the main metabolite of Dahl-S, glomerular filtration rate and systemic haematocrit did not differ between the strains before, during or after VE. To conclude, in spite of a defective renal DA1 receptor prehypertensive Dahl-S do not respond with an attenuated natriuretic or dopamine excretory response when subjected to a severe isotonic sodium load. The results do not support a sodium retaining role over a defective DA1 receptor in the salt-sensitive hypertension in Dahl-S.

3,4-Dihydroxyphenylacetic Acid

Effect on human teeth of renal transplantation: a postmortem study.

Extracted teeth from five deceased patients treated by renal transplantation were examined radiographically and histologically, and compared with teeth from healthy persons of approximately the same age. In three of the patients with a renal transplant, the radiographs showed normal pulp chamber sizes, but histologic examination revealed a widened predentin zone, approximately four times greater than in the controls. In two of the patients the radiographs showed marked reduction of the pulp chamber size. The histologic changes of these teeth were mainly an extensive amount of secondary dentin along the pulp chamber walls and the root canals, with a markedly reduced pulp space. One explanation for the difference between the patients was that patients with extensive pulp calcifications were given a higher total amount of corticosteroids than patients with a widened predentin zone.

Adult

[Promoting competence in a model trial of a complementary course of study in health sciences/public health at the Berlin Technical University in cooperation with the Free University and other science and general practice institutions].

Since October 1992 (winter semester 92/93) graduates are being educated in Public Health at Berlin Technical University in cooperation with the Free University of Berlin as well as with the Humboldt University of Berlin and other institutions of science and practice in Berlin and Brandenburg. For the time being the course of studies is a pilot project for 4 years. The aim of the postgraduate studies is the creation of permanent structures and therefore institutionalisation. It is open to graduates and college graduates of public-health relevant subject areas of specialisation are "Health Promotion in the community and at the workplace" and "Planning and Management in Health Services". The course of studies takes 4 semesters and is divided into basic studies, studies of main points of emphasis and project studies. Social medicine and especially epidemiology are part of the basic disciplines, which are indispensable for finding the way of looking at problems concerning public health. The reason for the peculiarity with regard to establishing public health at other German universities are the main topics representing the interaction between the technical and ecological development of health. The graduate degree is "Magister of Public Health". During the time of the pilot project the course of studies is subjected to external and internal surveillance regarding quality assurance and quality optimisation of teaching and organisation of the studies. On the one hand this is done by an external advisory committee and on the other hand by internal and external evaluation.

Community Medicine

Optical evaluation of red blood cell geometry using micropipette aspiration.

Although red blood cell (RBC) geometry has been extensively studied by micropipette aspiration, the small size of RBC and pipettes vs. the optical resolution of light microscopy suggests the need to consider potential errors. The present study addressed such difficulties and investigated four specific problems: (1) use of exact equations to calculate RBC membrane area and volume; (2) calibration of the pipette internal diameter (PID); (3) correction for a noncylindrical pipette barrel; (4) diffraction distortion of the RBC image. The observed PID represents a cylinder lens enlargement that can be theoretically derived from the glass/buffer refractive index ratio (1.49/1.33 = 1.12). This enlargement was experimentally confirmed by: (1) studying pipettes bent to allow measurement through the barrel (horizontal) and at the orifice (vertical), with a resulting diameter ratio of 1.12 +/- 0.01; (2) and by replacing the surrounding buffer with immersion oil and hence abolishing the lens phenomenon (ratio = 1.12 +/- 0.02). In addition, use of aspirated oil droplets demonstrated a 3.2 +/- 0.2% error when the PID is focused at a sharp, maximum diameter. The average pipette cone angle was 1.49 +/- 0.09 degrees and varied considerably with pipette pulling procedures; calculated tongue geometry inside the pipette was affected by the noncylindrical pipette barrel. The RBC diffraction error, demonstrated by touching two aspirated cells held by opposing pipettes, was 0.091 +/- 0.002 microns. The PID, cone angle, and diffraction artifacts significantly (p < 0.001) affected calculated RBC geometry (average errors up to 5.4% for area and 9.6% for volume). Two new methods to calculate, rather than directly measure, the PID from images of a single RBC, during either osmotic or pressure manipulation, were evaluated; the osmotic method closely predicted the PID, whereas the pressure method markedly underestimated the PID. Our results thus confirm the need to consider the above-mentioned phenomena when determining RBC geometric parameters via micropipette aspiration.

Algorithms

High level expression of functional full length human thyroid hormone receptor beta 1 in insect cells using a recombinant baculovirus.

We have cloned the human thyroid hormone receptor beta 1 (hThR beta) from the human breast cancer cell line T47D using the PCR technique. A recombinant baculovirus transfer vector pVL1392/hThR beta was constructed and the full length receptor was expressed in the insect cell line Spodoptera frugiperda (Sf9). Approx. 10-15 x 10(6) receptors are expressed/cell which implies a production level of 2.5-4.0 mg hThR beta/l of cell culture. The expressed hThR beta displayed a single class of binding sites for T3 with high affinity. Western blot analysis using a polyclonal antibody indicated that the molecular weight of the baculovirus expressed receptor is approx. 50 kDa. Crude nuclear extract of hThR beta labeled with [125I]T3 sedimented as a 4 S peak on a glycerol gradient. No receptor could be detected in the cytoplasm indicating its proper translocation to the nuclear compartment. An oligonucleotide containing a palindromic thyroid hormone response element is specifically recognized and retarded in a gel-mobility-shift assay in the presence of nuclear extract of Sf9 cells expressing hThR beta. These data suggest that hThR beta expressed in Sf9 cells is functional and displays characteristics virtually indistinguishable from those of the thyroid hormone receptor (ThR) extracted from mammalian cells. Furthermore, the data indicate that the baculovirus expression system is adequate for large-scale production of receptor for detailed structural and functional studies.

Animals

Ursodeoxycholic acid-induced changes of plasma and urinary bile acids in patients with primary biliary cirrhosis.

Ursodeoxycholic acid treatment of patients with primary biliary cirrhosis may lead to relief of pruritus and improvement of biochemical liver tests. The changes in serum and urinary bile acids induced by ursodeoxycholic acid treatment were studied. After 29 patients with primary biliary cirrhosis were treated with ursodeoxycholic acid (750 to 1,000 mg/day) for 6 to 12 mo because of an increase in ursodeoxycholic acid, total plasma bile acids increased from 30.5 +/- 6 mumol/L (mean +/- S.E.M.) to 52.7 +/- 11.7 mumol/L (p less than 0.01). The increase in total plasma bile acids correlated significantly with concentrations of plasma bile acid before treatment (p less than 0.01). The concentrations of endogenous bile acids decreased, mainly because of a decrease of cholic acid. During treatment, glycine conjugation increased and taurine conjugation decreased, whereas sulfation and glucuronidation of bile acids were unchanged. In 10 patients with primary biliary cirrhosis in stages III and IV, urinary excretion of bile acids was also studied. After treatment, ursodeoxycholic acid and its 3-beta isomer and C-1-hydroxylated and C-6-hydroxylated derivatives were also excreted. During treatment, urinary excretion of endogenous bile acids decreased. The increase of ursodeoxycholic acid and the decrease of endogenous bile acids may both be related to the improvement of biochemical liver tests in precirrhotic stages of the disease. In cirrhosis, endogenous bile acids in plasma remained high and changes in liver tests were small.

Bile Acids and Salts

Long-term follow-up of posttransfusion and sporadic chronic hepatitis non-A, non-B and frequency of circulating antibodies to hepatitis C virus (HCV).

The natural course of chronic hepatitis non-A, non-B (HNANB) was documented for 3-20 yr (mean 8 yr) in 86 patients, who attended our special ambulance between 1981 and 1988. Sixty five of the 86 patients (75%) were positive for circulating antibodies against hepatitis C virus (HCV) (anti-HCV). Twenty four patients had chronic posttransfusion (PT)-HNANB (18 anti-HCV-positive; 75%), and 62 patients had sporadic (S)-HNANB (47 anti-HCV-positive; 75%). Twenty nine per cent of patients with chronic PT-HNANB had sustained normalization of aminotransferases after a period up to 5 yr, 55% demonstrated chronic persistent hepatitis (CPH) and 16% progressed to chronic active hepatitis (CAH) with transition to cirrhosis. In the group with chronic S-HNANB, 2% of patients showed remission, 43% had stable CPH and 55% progressed to CAH or cirrhosis. However, development of cirrhotic complications required many years. Transition from CAH to CPH or remission was not observed. The results indicate that 75% of both patients groups with chronic PT- and S-HNANB are infected with the same agent, of which antibodies are detected by the new anti-HCV assay. There was no statistical association between the severity of the disease and the presence of anti-HCV. The different proportions of progressive courses in chronic PT- and S-HNANB might be explained by the patient recruitment.

Blood Transfusion

Liver membrane antibodies (LMA) recognize a 26-kD protein on the hepatocellular surface.

Sera from 82 patients with chronic inflammatory liver diseases and from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Hashimoto's thyroiditis were studied by immunoblotting against purified liver plasma membranes (LPM) and soluble liver protein (SLP) fractions from different species after previous separation by SDS-PAGE. Eighteen of 19 sera with LMA of IgG type in immunofluorescence assay and six LMA-negative sera (three sera from patients with RA) showed antibodies of the IgG or IgM classes against a protein with a molecular weight of 26 kD which was present in LPM and SLP fractions from rats, rabbits, pigs and humans. The reaction with 26-kD liver protein did not correlate with other known autoantibody-antigen systems. All sera were negative in the 26-kD region with liver mitochondria, liver microsomes and soluble proteins of kidney (with one exception), heart and gut from the rat. The 26-kD protein was purified by affinity chromatography on immobilized anti-26-kD protein antibodies from patients, eluted from the 26-kD band of immunoblots. Studies with purified 26-kD liver protein and with SLP as antigens after separation in two-dimensional electrophoresis confirmed that patient serum and experimental rabbit antiserum react with the same protein. Eluted patient antibodies and rabbit antisera showed a linear fluorescence pattern on isolated hepatocytes from rat and rabbit. The data indicate that one of the target antigens of LMA is a species-nonspecific 26-kD protein located on the hepatocellular surface.

Adolescent

Guinea pig maximization test with a polyether impression material.

Adverse reactions to a polyether rubber impression material introduced in the mid-sixties have been reported in the literature. Most of the reports are inconclusive regarding the distinction between allergic and toxic responses. The aim of this study was to assess the allergenic potential of this material using a guinea pig maximization test. Ten guinea pigs in the experimental group were sensitized in two steps. First, an extract of the material was injected intradermally, and 7 days later, the material mixed in petrolatum was applied topically. After another 2 wk test solutions were applied, and the skin response was evaluated by visual inspection. Ten nonsensitized animals served as controls. From the challenge test it was evident that the catalyst as well as the freshly mixed material elicited positive skin reactions interpreted as being delayed hypersensitivity reactions. The findings indicate that the material contained substances which could be classified as strong to extreme sensitizers. Some of the adverse reactions seen in connection with the use of this material might well be related to delayed hypersensitivity reactions.

Allergens

Antibody activity against lipopolysaccharides, lipid A and proteins from Enterobacteriaceae in patients with chronic inflammatory liver diseases.

These studies are concerned with detection of circulating antibodies against various defined enterobacterial antigens in patients with chronic inflammatory liver diseases such as chronic hepatitis type B (n = 46), chronic active hepatitis (CAH) of autoimmune type (n = 10), alcoholic cirrhosis (n = 24) and primary biliary cirrhosis (PBC) (n = 24) as well as in healthy individuals (n = 39). Anti-LPS and anti-lipid A were determined by hemolytic and hemagglutination assay. Immunoblot technique was used to investigate the antibody activity against plasmid encoded proteins from Yersinia enterocolitica. Persistent titers of anti-LPS up to serum dilution 1:32.768 were found with hemolytic and hemagglutination assay in patients with alcoholic cirrhosis or PBC and in healthy control. In contrast nearly 50% of patients with chronic hepatitis B had no hemolytic antibodies against the two LPS E. coli serotypes at the time of liver biopsy. Anti-lipid A was detectable in 58% of patients with alcoholic cirrhosis but in low titers in less than 10% in the other groups (p less than 0.001). Alcoholic cirrhosis was also associated with a high frequency of IgG and IgA antibodies against plasmid encoded proteins from Yersinia enterocolitica. The data indicate that the O-polysaccharides as strong antigens are physiologically exposed to the immune system while lipid A and enterobacterial proteins are solely immunogenic under abnormal conditions.

Adult

Experimental liver membrane antibodies (LMA) and antibodies against "liver specific protein (LSP)"--a comparative in vitro study.

Experimental antisera against the 26 kD rat liver protein--recently defined as a target antigen of LMA--and against "LSP" were tested on tissue sections and isolated hepatocytes from rat as well as with a variety of subcellular fractions as antigens. Anti-26 kD protein resulted in sharp immunofluorescence staining of hepatocellular plasma membranes in liver sections and on isolated hepatocytes, while the antiserum did not react with intracellular structures and was also negative with tissue sections from kidney and heart. Anti-"LSP" stained the plasma membranes of isolated hepatocytes, the cytoplasma of liver and kidney sections as well as the connective tissue of heart sections. In Western blot studies anti-26 kD protein showed a single band at 26 kD when liver plasma membranes and soluble liver protein fractions were used as antigens; a weak reaction was observed with microsomes and soluble kidney protein fractions, but there was no reaction with mitochondria or soluble heart proteins. Anti-"LSP" reacted with various proteins of the subcellular fractions between 16 and 116 kD. The 26 kD protein was found in peak II of Sepharose 6B chromatography of soluble liver protein fractions but was absent in the "LSP" fraction (peak I). We conclude that experimental LMA and anti-"LSP" recognize different epitopes of the hepatocellular plasma membrane.

Animals

Glycoproteins of rat liver plasma membranes: their hepatocellular, intestinal and renal expression in rat, rabbit and human.

Expression of six glycoproteins (Mr = 60,000 (gp 60), 80,000 (gp 80), 110,000 (gp 110), 120,000 (gp 120), 140,000 (gp 140), 160,000 (gp 160)) recently purified from rat liver plasma membranes (LPM) were compared in the liver, small intestine and kidney of the rat, rabbit and human. Immunoblotting studies with monospecific antisera showed that five of the six glycoproteins (gp 60, gp 80, gp 110, gp 120, and gp 140) were expressed not only in LPM of the rat but also in LPM from the rabbit and human with Mr corresponding to those of the glycoproteins isolated from the rat. In contrast, the glycoprotein gp 160 was only detected in rat liver. The same pattern of expression was found by immunofluorescence on isolated hepatocytes from the three species. In rat liver, the glycoproteins were localized primarily either in the bile canalicular domain (gp 80, gp 110, gp 120), or in the sinusoidal domain (gp 60, gp 140), or they were distributed over the whole hepatocellular surface (gp 160). In rat, but not in rabbit or human, the glycoproteins gp 110, gp 120 and gp 140 were also found in the small intestine localized either in the brush border membrane (gp 110, gp 120) or over the whole surface membrane of enterocytes (gp 140). Gp 120 was also detected in the luminal pole of tubular epithelial cells of rats kidney. The data show that LPM of different mammalian species share several common glycoprotein antigens. These glycoproteins, that are also partly expressed in extrahepatic tissues, may represent plasma membrane structures conserved among mammalian species.

Animals

[Long-term treatment of cryptogenic hepatitis C using recombinant interferon alpha].

In a pilot study 15 patients with cryptogenic chronic hepatitis non-A, non-B received human recombinant interferon alpha (rIFNa) at a dosage of 5 million units 3 times per week for periods of up to 4 months, followed by an additional 4-month course of treatment with 2 million units 3 times per week after an observed reduction in serum aminotransferase levels. Ten of the 15 patients demonstrated antibodies to hepatitis C virus (HCV). Pretreatment histological examinations revealed evidence of chronic aggressive hepatitis in 12 patients, 4 with signs of cirrhosis, and chronic persistent hepatitis (CPH) in the remaining 3 cases. Normalization of serum aminotransferase levels was documented in 9 patients (7 anti-HCV-positive), and a significant reduction occurred in 2 additional anti-HCV-positive cases. Follow-up biopsy at 8 months in 7 of the 11 responders documented improved histological findings in every case. Five patients with CAH in the initial study had discrete residual portal inflammation or mesenchymal reaction in the second histological examination. Clinical follow-up is currently at 12 month, and 3 anti-HCV-positive responders have normal aminotransferase levels. The data show that a subset of patients with chronic hepatitis C will demonstrate remission of disease after an 8-month course of treatment with rIFNa.

Adult