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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 379 records · Page 21Linked to original sources
PubMed1995

Manifestation late in life of idiopathic adulthood ductopenia.

Idiopathic adulthood ductopenia is a chronic cholestasic liver disease of unknown etiology characterized by the loss of interlobular bile ducts. We describe three patients who fulfilled the diagnostic criteria of idiopathic adulthood ductopenia, but differed from the cases reported so far in late manifestation of the disease and a benign clinical course despite histologic evidence of ongoing cholangitis. Treatment with ursodeoxycholic acid in one patient resulted in improvement of biochemical markers of cholestasis, suggesting that chronic cholestasis in idiopathic adulthood ductopenia can be influenced beneficially.

Aged↗
PubMed1995

Characterization of a 2,3-dihydroxybiphenyl dioxygenase from the naphthalenesulfonate-degrading bacterium strain BN6.

An extradiol dioxygenase was cloned from the naphthalenesulfonate-degrading bacterial strain BN6 by screening a gene bank for colonies with 2,3-dihydroxybiphenyl dioxygenase activity. DNA sequence analysis of a 1,358-bp fragment revealed an open reading frame of only 486 bp. This is the smallest gene encoding an extradiol dioxygenase found until now. Expression of the gene in a T7 expression vector enabled purification of the enzyme. Gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that the protein was a dimer with a subunit size of 21.7 kDa. The enzyme oxidized 2,3-dihydroxybiphenyl, 3-isopropylcatechol, 3- and 4-chlorocatechol, and 3- and 4-methylcatechol. Since the ability to convert 3-chlorocatechol is an unusual characteristic for an extradiol-cleaving dioxygenase, this reaction was analyzed in more detail. The deduced amino-terminal amino acid sequence differed from the corresponding sequence of the 1,2-dihydroxynaphthalene dioxygenase, which had been determined earlier from the enzyme purified from this strain. This indicates that strain BN6 carries at least two different extradiol dioxygenases.

Amino Acid Sequence↗
PubMed1995

Extent of disease based on initial bone scan: important prognostic predictor for patients with metastatic prostatic cancer. Experience from the Scandinavian Prostatic Cancer Group Study No. 2 (SPCG-2).

The skeleton is the most frequent site of metastases from prostate cancer. Quantitation of the amount of tumor burden has a great prognostic value and is of importance for clinical trials. The present study reviews 194 bone scans from the SPCG-2 study which consisted of 294 patients entered into a randomized prospective multicenter trial, comparing total androgen suppression with standard treatment in patients with metastatic prostatic cancer (orchiectomy plus cyproterone acetate vs. orchiectomy plus placebo). Evaluation of the initial bone scans based on the extension of the disease (EOD) as proposed by Soloway and associates gives a convenient stratification of the patients. With regard to time to progression and cancer-related as well as overall survival, this EOD grading system had a significant prognostic value (p < 0.001). There was no statistical difference between the two treatment arms in the different categories of the EOD grading system with regard to time to progression and time to death. By analyzing exclusively the subgroup of patients with minimal disease (EOD I) and good performance status (WHO score 0), there was a nonsignificant trend toward a better 2-year progression-free survival as well as a better 2-year cancer-related survival for those who were subjected to total androgen suppression as compared with the patients subjected to the standard treatment (orchiectomy).

Androgen Antagonists↗
PubMed1995

Technetium-99m-galactosyl-neoglycoalbumin combined with iodine-123-Tyr-(A14)-insulin visualizes human hepatocellular carcinomas.

UNLABELLED: Human hepatocellular carcinoma (HCC) is the most frequent primary hepatic malignancy and its diagnosis by conventional methods is still difficult. We hypothesized that the expression of specific receptors could possibly be used to improve in vivo localization of HCC with specific receptor-based radioligands. METHODS: In initial in vitro studies, receptor binding of 99mTc-galactosyl-neoglycoalbumin (99mTc-NGA) and 123I-Tyr-(A14)-insulin to HCC was investigated. Scintigraphy was performed in 45 patients with histologically confirmed HCC using either 99mTc-NGA (75-150 MBq; 25-50 nmole, n = 27) and/or 123I-Tyr-(A14)-insulin (100-150 MBq; 7.5-10 micrograms, n = 30). RESULTS: HCC (1256 +/- 290 pmole bound/mg protein, Kd = 3.4 +/- 2.9 nM) expressed a 1000-fold higher number of specific receptors for 123I-Tyr-(A14)-insulin compared to normal liver tissue (2.4 +/- 0.8 pmole bound/mg protein, Kd = 4.2 +/- 2.4 nM), whereas HCC did not express receptors specific for 99mTc-NGA. All HCC lesions were identified as cold spots after injection of 99mTc-NGA, whereas 123I-Tyr-(A14)-insulin accumulated in these lesions, indicating HCC-to-normal liver ratios of 1.6 +/- 0.4 in the mean. Subtraction images obtained from planar studies visualized 123I-Tyr-(A14)-insulin in HCC lesions detected by 99mTc-NGA as cold spots. CONCLUSION: This hepatocyte receptor-specific, double-tracer method using 99mTc-NGA and 123I-Tyr-(A14)-insulin could become clinically useful in the diagnosis of HCC.

Aged↗
PubMed1995

[Recurrent multiple leiomyomatous hamartomas of the lung].

A 40 year old female was operated because of pulmonary leiomyomatous hamartoma. Despite repeated surgical resection therapy during the following years she developed recurrent multiple hamartoma. The indication for multiple surgery only included compression of central vessels or rapid growth of the hamartomas. The history of hysterectomy--as in our patient--is common for patients with multiple leiomyomatous pulmonary hamartoma. However, revision of the histological slides revealed no hint of uterine leiomyosarcoma. Therefore, a primary pulmonal (and recurrent) multiple hamartosis seems obvious.

Adult↗
PubMed1995

[Morbidity and long-term survival after bronchoplastic resection of non-small-cell bronchial carcinoma].

During the past 12 years, among 1384 operations for NSCLC, 96 (6.9%) bronchoplastic resections were performed. There were 68 lobectomies, 19 bilobectomies and 9 pneumonectomies done by means of 66 sleeve resections, 28 wedge resections and 2 resections of the tracheal bifurcation. Atelectasis and anastomotic dehiscence were observed in 5 and 4%, respectively. A local complete resection was achieved in 81%. The 30-day mortality was 4%. The results show, that bronchoplastic procedures represent a safe therapeutic option in the operative treatment of centrally located NSCLC.

Aged↗
PubMed1995

Improved hepatocyte in vitro maintenance in a culture model with woven multicompartment capillary systems: electron microscopy studies.

Primary pig hepatocytes form a tissuelike structure in an in vitro culture model that has provision for three-dimensional cell orientation, cell aggregation, decentralized cell perfusion with low metabolite gradients, integral oxygenation, and nonparenchymal cell coculture. Scanning electron microscopy (SEM) has shown that hepatocytes spontaneously form aggregates in a three-dimensional structure between and on the surface of artificial capillaries. Transmission electron microscopy (TEM) has shown that after 7 weeks of in vitro perfusion, the cell ultrastructure remains similar to that of the parenchyma in vivo. Golgi complexes, active membrane processes, reorganization of cell junctions, and bile canaliculi-like intercellular spaces were demonstrated.

Animals↗
PubMed1995

[Increased vagal activity after administration of the calcium antagonist diltiazem in patients with coronary heart disease].

The effects of the calcium channel blockers diltiazem on the parasympathetic nervous system were studied by using spectral analysis of heart rate variability, and were compared with the effects of the beta-receptor blocker metoprolol. The area under the curve of the high-frequency range (f = 0.18-0.35 Hz) during controlled respiratory rate (f = 0.25 Hz) was used as a quantitative index of parasympathetic activity. Twenty-four male patients with proven coronary artery disease and normal left ventricular function (LVEF > 60%) were studied 2 weeks after chronic treatment with diltiazem (3 x 60 mg daily) or metoprolol (3 x 50 mg daily) before and after administration of the drug. Twelve patients received diltiazem and 12 patients metoprolol. After administration of diltiazem the peripheral systolic blood pressure was reduced, but the parasympathetic activity was significantly higher than compared with the initial measurement. The same effect was seen for metoprolol, but a significant lower heart rate was present after administration. The relative area under the high-frequency range significantly increased at rest, by 110% after diltiazem and 70% after metoprolol. Diltiazem and metoprolol enhance the vagal influence at the heart, thereby leading to an enhancement of barosensitivity and of the respiratory sinus arrhythmia. This action may contribute to the beneficial effects of both drugs in patients with coronary artery disease.

Aged↗
PubMed1995

Regulation of phosphoinositide hydrolysis and cytosolic free calcium induced by endothelin in human glomerular epithelial cells.

The regulation of the inositide signalling pathway and [Ca2+]i by endothelin (ET) peptides was investigated in human glomerular epithelial cells in culture. Endothelin-1 and -2 induced an accumulation of inositol phosphates in a time- and dose-dependent manner. The baseline of [Ca2+]i in glomerular epithelial cells was 109 +/- 2.8 nmol/l, n = 60. Endothelin-1 (ED50: approx. 3 x 10(-9) mol/l) caused a rapid and transient rise in [Ca2+]i as detected by fura-2 microfluorimetry studies. The endothelin-1-induced inositol phosphate accumulation was inhibited by the selective ETA receptor antagonist BQ123. Endothelin-3 and BQ3020, a selective ETB receptor agonist, showed no effect. The results suggest an ETA-mediated pathway. This study demonstrates an ETA-mediated transmembrane signalling via phospholipase C with consecutive elevation of inositol phosphates and intracellular calcium. Since endothelin peptides contribute to both normal renal function and renal dysfunction, this study adds further knowledge on glomerular cell regulation.

Calcium↗
PubMed1994

Bioreactor for a larger scale hepatocyte in vitro perfusion.

A bioreactor construction for hepatocytes and liver sinusoidal endothelial cells is described. The reactor is based on capillaries for hepatocyte immobilization. Four discrete capillary membrane systems, each serving different purposes, are woven to create a three-dimensional framework for decentralized cell perfusion with low metabolite gradients and decentralized oxygenation and CO2 removal. The biochemical performance of reactors initially seeded with 2.5 x 10(9) hepatocytes were evaluated over 3 weeks. On day 21, pig albumin synthesis was 4.7 mg/day, lidocaine metabolism was 813.7 +/- 23 micrograms/hr, galactose elimination was 210.1 +/- 3 mg/hr, and midazolam metabolism was 37.1 +/- 2 micrograms/hr. The specific construction of the reactor enables scale-up to hybrid liver support systems as extracorporeal bridging devices for liver transplantation.

Animals↗
PubMed1994

Aerobic biodegradation of 3-aminobenzoate by gram-negative bacteria involves intermediate formation of 5-aminosalicylate as ring-cleavage substrate.

The aerobic metabolism of 3-aminobenzoate by bacteria was studied. Bacterial strains degrading 3-aminobenzoate were obtained by enrichment with 3-aminobenzoate (strain Ia3) or 5-aminosalicylate (strains BN9 and 5AS1). During growth with 3-aminobenzoate, strain Ia3 and strain 5AS1 transiently accumulated 5-aminosalicylate in the culture broth. In the presence of inhibitors of 5-aminosalicylate 1,2-dioxygenase, resting cells of all three strains converted 3-aminobenzoate to stoichiometric amounts of 5-aminosalicylate. 5-Aminosalicylate 1,2-dioxygenase activity was induced in all strains after growth with 3-aminobenzoate or 5-aminosalicylate, but not after growth in complex media.

Aminobenzoates↗
PubMed1994

Resistance of CTL to perforin-mediated lysis. Evidence for a lymphocyte membrane protein interacting with perforin.

Cytotoxic T lymphocytes are highly resistant to killing by their own cytolytic protein perforin. We have investigated the molecular basis of this self-protection mechanism. CTL withstood high dosages of perforin, when complete lysis was obtained with various tumor target cell lines. A peptide-specific CTL clone readily lysed tumor targets presenting the peptide, but was unable to kill the peptide-presenting CTL in spite of equal degranulation. With streptolysin O, a pore-forming lytic protein of bacterial origin, no difference in susceptibility between the various targets was detected. Perforin was radioactively labeled by using the Bolton and Hunter method without any loss of its lytic activity. Experiments performed at 4 degrees C revealed that, on all of the cells studied, binding of the labeled perforin to the membrane is reversible and strictly Ca(2+)-dependent. After a short exposure to 37 degrees C, perforin was no longer dissociated from cell membranes by EDTA. Although no correlation between susceptibility and the extent of perforin binding was detected, differences in the conformation of membrane-bound perforin were observed. Perforin adsorbed to resistant cells was cleaved by trypsin into a 55-kDa (C-terminal) and a 10- to 15-kDa (N-terminal) fragment, whereas this cleavage was not found on tumor cell-bound perforin. A portion of perforin was included in the Triton X-114 detergent phase at 4 degrees C on resistant CTLs only. Our results are compatible with the notion that a protective molecule, specifically expressed on CTLs, interacts with perforin, thereby rendering it lytically inactive.

Animals↗