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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 415 records · Page 23Linked to original sources
PubMed1994

Hybrid liver support system in a short term application on hepatectomized pigs.

A short term application of a hybrid liver support system in circuits with continuous plasma-separation was investigated in a model of hepatectomized pigs under general anesthesia. Primary pig hepatocytes were immobilized in a bioreactor with three independent capillary systems. An immune barrier is achieved by avoiding the direct contact of blood cells with the hepatocytes by a plasmaseparation step and by an outflow filtration within the reactor. In three groups (hepatectomized pigs and system with- or without hepatocytes as well as untreated pigs with system without hepatocytes), the short term metabolism of the reactors was positively demonstrated by investigating ammonia detoxification, phenylalanine- and lactate metabolism. Limitations of the presented model are discussed.

Ammonia↗
PubMed1994

In-vitro biocompatibility of alternative CAPD fluids; comparison of bicarbonate-buffered and glucose-polymer-based solutions.

Evidence is accumulating that conventional dialysis fluids for CAPD are incompatible with peritoneal host defence. We therefore investigated the effect of alternative CAPD fluids on mononuclear leukocyte (PBMC) viability and cytokine production in vitro. Fluids tested were bicarbonate-buffered solutions containing 1.5% or 4.25% glucose, 7.5% glucose polymer dialysis fluid (GPDF), and conventional 1.5% glucose fluid (G1.5%). PBMC were stimulated (2 h, 37 degrees C) in the different test fluids with a clinical isolate of Staphylococcus epidermidis or Escherichia coli lipopolysaccharide. The cytokines TNF alpha and IL-6 in PBMC supernatants were measured by specific enzyme immunoassays. Induction of cytokine messenger RNA was evaluated by reverse transcription-polymerase chain reaction. Conventional G1.5% (pH 5.5) inhibited cytokine release from activated PBMC by > 95%, whereas cell responses in low-glucose bicarbonate fluid were not significantly reduced. In contrast, high-glucose bicarbonate fluid exerted > 80% inhibition despite its neutral pH. GPDF was inhibitory at its initial low pH, whereas cytokine release was restored following pH neutralization. Cytokine mRNA expression was suppressed by conventional G1.5% fluid and by high-glucose bicarbonate fluid. These data indicate that pH neutralization leads to a substantial improvement of dialysis fluid biocompatibility; however, hyperosmolality and/or high glucose content inhibit cell responsiveness even at normal pH. Replacement of glucose by glucose polymer might prove beneficial provided that the initial low pH is neutralized.

Actins↗
PubMed1994

[Cell culture model for hepatocyte culture in bioreactors for metabolic utilization in hybrid liver support system].

Hybrid systems with hepatocyte cultures in bioreactors are in development for therapeutical liver assistance. Here, a culture model with a special bioreactor construction was developed: Capillary membrane systems create a three dimensional artificial framework for hepatocyte adhesion, aggregation and reorganization of tissue structures. Many of small parallel capillary membrane units perfuse a few hepatocytes. Different capillary materials enable different functions. Cell perfusion between independent plasma inflow and outflow capillaries, independent oxygen supply and carbon dioxide removal as well as a co- culture with sinusoidal endothelial cells are possible. An in vitro study with bioreactors (n = 9), containing 2.5 x 10(9) pig hepatocytes was performed, measuring external metabolism of the cells: cytochrome P450-activity (midazolam metabolism, lidocaine/MEGX-test), synthesis (albumin), liver function test (galactose elimination) and cell alteration (LDH, GOT, GLDH, GPT, gamma GT) were investigated. The results demonstrate that external function of primary hepatocytes can be maintained over a period of at least three weeks.

Animals↗
PubMed1994

[Follow-up of heterotopic autotransplantation of splenic tissue after traumatic splenic rupture in childhood].

Children and adolescents, who received an autologous reimplant of the spleen because of traumatic injury between 1979 and 1986 were matched to a cohort of patients, splenectomized because of traumatic injury of the spleen as well and to a control group of healthy age matched individuals. In addition to a physical check-up, markers of humoral and cellular immunity (e.g. lymphocyte subpopulations and phagocytosis of pneumococcy) as well as the coagulatory and fibrinolytic system were examined. All parameters tested, were found to between results from splenectomized and healthy individuals. Our studies stress the fundamental ability of autologous spleen transplants to take over part of the splenic function on the basis of a largerly histomorphologic restitution. Thus autologous reimplantation of the spleen in children and adolescents is an excellent choice as compared to otherwise necessary splenectomy, if preservation of the organ is impossible.

Adolescent↗
PubMed1994

Pathogenesis of chronic renal failure in primary glomerulopathies.

Comparative analysis of renal biopsy findings and clinical status in patients with different types of glomerulopathy (primary glomerulonephritis, 1747; diabetic glomerulosclerosis, 488; renal AA and AL amyloidosis, 225) was undertaken to investigate the pathogenesis of chronic renal failure in these diseases. Morphometric, cytological and electron-microscopic investigations were undertaken and yielded the following results: 1. Disease of the renal corpuscles alone, even if it is very severe, does not lead to renal insufficiency or even elevation of the serum creatinine concentration. 2. Chronic renal insufficiency develops only in those cases of glomerulopathy in which the postglomerular capillaries in the renal cortex exhibit chronic inflammation that causes such severe narrowing of these vessels as to impair glomerular perfusion. 3. The passage of basement membrane material from the glomerular capillaries into the primary urine may play a critical role in the pathogenesis of some forms of chronic renal failure, since this material can be reabsorbed by the tubules and is probably presented as an autoantigen to intraepithelial T lymphocytes by proximal tubular epithelial cells that express distinct HLA class II antigens and ICAM-1. 4. The presentation of these autoantigens to intraepithelial T lymphocytes leads in genetically predisposed individuals to an autoimmune response with a consequent marked increase in numbers of T lymphocytes and an increase in macrophages/monocytes, fibroblasts/fibrocytes and plasma cells, and increased production of extracellular matrix by fibroblasts/fibrocytes. 5. The increase in extracellular matrix leads to obliteration of the postglomerular capillaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Capillaries↗
PubMed1994

The incidence, pathogenesis, diagnosis, and treatment of fat embolism.

Fat embolism syndrome is a potentially serious and life threatening complication of long bone trauma, blunt trauma, and intramedullary manipulation. In long bone fractures, fat embolism is encountered in 0.9% to 2.2% of cases. During intramedullary manipulations, such as prosthetic stem insertion or reaming, the incidence is typically lower (range, 0.5% to 0.8%). Diagnosis is dependent upon the clinical recognition of dyspnea, petechiae, and cognitive dysfunction in the first several days following fracture, trauma, or intramedullary surgery. Treatment consists of pulmonary support and aggressive resuscitation. Studies support early fracture fixation, but the role of systemic steroids, heparin, and other modalities remains speculative.

Brain Diseases↗
PubMed1993

DNA fragmentation during apoptosis is caused by frequent single-strand cuts.

One of the hallmarks of apoptosis is the digestion of genomic DNA by an endonuclease, generating a ladder of small fragments of double-stranded DNA. We have examined the nature of the DNA breaks produced in mouse thymocytes triggered to undergo apoptosis by steroids or by stimulation of the T cell receptor. Whereas the typical ladder pattern of oligonucleosomal fragments was observed after agarose gel electrophoresis, numerous single-strand cuts were detected after electrophoresis under denaturing conditions. Single-strand nicks were found to be very frequent in the internucleosomal regions, but also to occur in the core particle-associated DNA. An identical pattern of single-strand nicks was obtained when chromatin DNA was exposed to the single-strand cleaving deoxyribonuclease I. The nicked DNA fragments, extracted from apoptotic thymocytes, were sensitive to the action of S1-nuclease. We propose that DNA fragmentation induced during apoptosis is not due to a double-strand cutting enzyme as previously postulated, but rather is the result of single-strand breaks. This ensures the dissociation of the DNA molecule at sites where cuts are found within close proximity.

Animals↗
PubMed1993

Effect of trifluoromethyl and other substituents on activity of xanthines at adenosine receptors.

An aryl p-(trifluoromethyl) substituent increases the affinity of 1,3-disubstituted 8-phenylxanthines at A2a-adenosine receptors, while having little effect on affinity at A1-adenosine receptors. In contrast, an aryl p-(trifluoromethyl) substituent has little effect on affinity of 3,7-disubstituted and 1,3,7-trisubstituted 8-phenylxanthines. An aryl p-sulfo substituent reduces affinity of all 8-phenylxanthines at A1- and A2a-adenosine receptors. An 8-(trifluoromethyl) substituent markedly reduces affinity of 1,3-dialkylxanthines at both A1- and A2a-adenosine receptors. In contrast, 8-(trifluoromethyl)caffeine retains affinity for A2a-adenosine receptors, but does lose affinity for A1-adenosine receptors. 8-Bromo-, 8-acryl-, and 8-pent-1-enylcaffeines are also selective for A2-adenosine receptors, while 8-cyclobutylcaffeine is nonselective. 8-[trans-2-(tert-butyloxycarbonyl)vinylcaffeine is 20-fold selective for Aza vs A1 receptors.

Acylation↗
PubMed1993

The NF-M transcription factor is related to C/EBP beta and plays a role in signal transduction, differentiation and leukemogenesis of avian myelomonocytic cells.

Retroviral oncogenes encode nuclear regulators of gene expression or signal transduction molecules, such as protein kinases, which stimulate the activity of cellular transcription factors. Here we describe the cloning of NF-M, a myeloid-specific transcription factor related to C/EBP beta, which is a target of activated protein kinases. NF-M stimulates the expression of the gene encoding cMGF, a myeloid cell-specific growth factor, creating an autocrine growth loop crucial to oncogene transformation of myeloid cells. The NF-M protein bound directly to the cMGF gene promoter and activated its transcription, even in erythroid cells where the promoter is usually inactive. In addition, a truncated, dominant-negative form of NF-M inhibited cMGF expression in macrophages, indicating that NF-M is required for the normal activation of the gene. When multipotent hematopoietic progenitor cells were stimulated to differentiate, NF-M expression was induced at a very early stage, suggesting that the transcription factor plays a role in lineage commitment. The stimulation of transformed myelomonocytic cells or of normal peripheral blood macrophages with kinases or LPS or TPA respectively, led to the rapid redistribution of NF-M protein from the cell bodies to the nucleus, consistent with the notion that NF-M was directly affected by such treatments. Our data indicate that NF-M plays a key role in myelomonocytic differentiation, in signal transduction during macrophage activation and in the development of myelogenous leukemia.

Amino Acid Sequence↗
PubMed1993

Preclinical detection of initial vestibulocochlear abnormalities in a patient with multiple sclerosis.

A 49-year-old woman presented with a third-degree continuous spontaneous nystagmus to the left which was followed by a sudden, almost complete deafness of her left ear. These symptoms were established as the sole initial presenting manifestations of multiple sclerosis (MS). Magnetic resonance imaging demonstrated a lesion within the left eight nerve root-entry zone and multiple small central lesions beneath the lateral ventricles. Pure-tone audiometry returned to normalcy after 2 weeks and speech discrimination was 100% after 10 weeks. Auditory brainstem responses (ABRs) showed abnormal parameters during a 10-month follow-up period after the acute hearing loss. Furthermore, desynchronization in ABR testing could be demonstrated 2 days before onset of hearing loss, which was interpreted as a prodromal ABR sign of the incipient MS attack.

Adult↗
PubMed1993

Molecular analysis of HLA-B39 subtypes.

Serological studies have suggested the presence of a new HLA-B39 subtype (B39.2) in the Japanese population. To identify the new HLA-B39 subtype and compare it with an other HLA-B39 subtype (B39.1), the genes encoding HLA-B39.1 (B*39013) and B39.2 (B*3902) have been cloned from Japanese. We have sequenced these genes and completed the sequence of HLA-B39.1 (B*39011) gene from a Caucasian that was partially sequenced. Comparison of the sequence data revealed that B*3902 and B*39013 differ by three nucleotide substitutions which result in a two amino acids change at residues 63 and 67, while one silent substitution at codon 312 is found between B*39011 and B*39013. These results suggest that B*3902 has evolved from B*39013 rather than B*39011.

Amino Acid Sequence↗
PubMed1993

Reduced production of immunoreactive interleukin-1 by peripheral blood monocytes of patients with acute and chronic viral hepatitis.

The in vitro production of interleukin-1 beta by peripheral blood monocytes derived from patients with various liver diseases was studied. An impaired production of immunoreactive interleukin-1 (IL-1) (mean +/- SEM) by monocytes stimulated with an optimal dose (100 ng/ml) of lipopolysaccharide was observed in patients with chronic hepatitis B (N = 13; 32 +/- 6 pg/ml) or chronic hepatitis C (N = 13; 61 +/- 12 pg/ml) as compared to those of healthy control individuals (N = 35; 166 +/- 24 pg/ml; P = 0.0003 and P = 0.015, respectively), whereas an unaltered IL-1 production was seen in patients with alcoholic cirrhosis (N = 23; 125 +/- 28 pg/ml) and primary biliary cirrhosis (N = 6; 111 +/- 33 pg/ml). Similar to the situation seen in chronic viral hepatitis, lipopolysaccharide-stimulated monocytes from patients with acute hepatitis also showed a decreased IL-1 production in the first week after onset of jaundice (N = 17; 55 +/- 20 pg/ml; P = 0.001) and a return to normal in the second and third week. An impaired production of IL-1 in chronic as well as acute viral hepatitis is a further example of the known disturbed immunoregulation in this disease.

Acute Disease↗