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Biomedical subjects

J Müller

Publications and source records attributed to J Müller.

At least 487 records · Page 27Linked to original sources
PubMed1991

Two forms of cytochrome P-450(11 beta) in rat zona glomerulosa cells: a short review.

Aldosterone, the major mineralocorticoid hormone, is produced exclusively in the zona glomerulosa of the mammalian adrenal cortex. In the rat species, this zonal specificity of aldosterone biosynthesis appears to be due mainly to the existence of a second form of cytochrome P-450(11 beta), which differs from the major form of the enzyme (molecular weight 51,000) by (1) a lower molecular weight (49,000), (2) a broader range of catalytic activities, which include corticosterone methyl oxidation 1 and 2, (3) an exclusive occurrence in the zona glomerulosa, and (4) a crucial dependence on sodium and potassium intake. The 49K form of the enzyme can be induced by potassium ions in vivo (potassium repletion of potassium-deficient rats) or in vitro (primary cell culture). The biosynthesis of this protein is controlled most likely at the level of transcription. According to indirect evidence, ACTH induces only the 51K form of the enzyme in vitro. Prolonged treatment of rats with a high dose of ACTH has a repressive effect on the 49K form of the enzyme.

Animals↗
PubMed1991

Regulation of aldosterone biosynthesis: a continual challenge.

Aldosterone secretion by the zona glomerulosa of the adrenal cortex is directly influenced by a large, growing number of different physiologic agents. Their action includes: 1) acute stimulation or inhibition of early biosynthetic steps; 2) long-term activation or suppression of late biosynthetic steps; and 3) induction of growth or atrophy of zona glomerulosa cells. In rats, adaptation of late steps of aldosterone biosynthesis to sodium and potassium intake is mediated by the induction or repression of a second form of cytochrome P-45011 beta, which differs from the main form of the enzyme by a lower molecular weight and a greater range of catalytic properties.

Aldosterone↗
PubMed1991

The reaction of pristane (2,6,10,14-tetramethylpentadecane) with radiolytically generated reactive oxygen intermediates results in a stable genotoxic compound as assessed by the SOS chromotest.

The most widely studied model of plasmacytomagenesis is the induction of plasmacytomas in BALB/c mice by i.p. injections of the isoalkane pristane (2,6,10,14-tetramethylpentadecane). Employing a simple quantitative and well-established short-term bacterial genotoxicity assay, the SOS chromotest, as a model system, we have investigated whether pristane may potentially be involved in causing or modulating the genotoxic events thought to induce plasma cell tumorigenesis. We found that incorporation of pristane into the cell membranes enhance the SOS response in Escherichia coli PQ37 and PQ300 induced by gamma-radiation under hyperoxic conditions. Moreover, the oxidation of pristane by radiolytically generated reactive oxygen intermediates yielded a stable, genotoxic product active on E. coli PQ300, a SOS tester strain designed to detect oxidative genotoxins. We discuss these findings in relation to the tumor-promoting role of the chronic i.p. inflammation that accompanies plasmacytomagenesis and conclude that, under these specific conditions, pristane may possess a previously unrecognized genotoxic activity in its tumorigenic potential.

Carcinogens↗
PubMed1991

Effects of volatile anesthetics on cytoplasmic Ca2+ signaling and transmitter release in a neural cell line.

To provide new insights into the effects of volatile agents on the basic regulatory events involved in cytoplasmic free Ca2+ ([Ca2+]i) and stimulus-secretion coupling, the well-characterized clonal rat pheochromocytoma cell line PC12 was chosen as an experimental model. This cell line possesses nicotinic and muscarinic receptors, L-type voltage-operated channels (VOCs), and receptor-operated Ca2+ channels (ROCs). A PC12 variant, defective in nicotinic response, made it possible to study the influx-independent inositol trisphosphate-mediated intracellular Ca2+ release that is triggered by muscarinic receptor stimulation. [Ca2+]i was measured with the fluorescent Ca2+ indicator fura-2. Dopamine and norepinephrine secretion were determined by high-performance liquid chromatography. High K+ and nicotinic-receptor-induced [Ca2+]i increase and catecholamine secretion were inhibited by halothane, enflurane, isoflurane, and methoxyflurane in a dose-dependent manner; half-maximal inhibition (IC50) occurred within the clinically relevant concentration range. The inhibition was reversible after wash-out of anesthetic; was not restricted to dihydropyridine-sensitive L-type VOCs; and could not be overcome by increasing extracellular Ca2+. The inhibitory mechanisms of volatile anesthetics therefore differed from those of classical organic Ca2(+)-channel blockers, a difference also reflected by the differing Hill coefficients found for both substance groups. In contrast, the muscarinic-receptor-evoked internal Ca2+ release remained unimpaired, and secretion even increased under anesthetic exposure. In conclusion, the current study provides evidence that volatile anesthetics depress the Ca2+ influx through at least two independent Ca2+ channels, one of which proved insensitive to the dihydropyridine Ca2(+)-channel blocker nifedipine. This is particularly noteworthy, since dihydropyridine-insensitive N-type VOCs, so far found exclusively in neurons, are assumed to play a dominant role in synaptic transmission, which, although resistant to dihydropyridine inhibition, is effectively blocked by volatile anesthetics.

Anesthetics↗
PubMed1991

Rapid clearance of Candida albicans mannan antigens by liver and spleen in contrast to prolonged circulation of Cryptococcus neoformans antigens.

Clearances of mannan antigen from Candida albicans and glucuronoxylomannan antigen from Cryptococcus neoformans were examined in nonimmune rabbits by using self-prepared latex agglutination tests. Injected intravenously, 20 mg of Candida mannan antigen was cleared from the serum with a half-life of approximately 2 h. In contrast, 20 micrograms of Cryptococcus glucuronoxylomannan antigen had a half-life in serum of approximately 24 h. At the latest, 9 h after injection, both antigens were no longer detectable without pretreatment of serum samples with protease and heating to 100 degrees C, thus indicating rapid binding by serum proteins other than immunoglobulins. Candida mannan antigen clearance was also examined in nonimmune mice after intravenous injection of (i) 200 micrograms of Candida mannan antigen, which accumulated in the liver and spleen and persisted for 97 days; (ii) 2 x 10(7) ethanol-killed Candida blastospores, which was accompanied by rapid clearance of mannan from the blood but accumulation of mannan in the liver and spleen and slow clearance from these organs; (iii) 6 x 10(6) viable C. albicans cells (lethal infection), which resulted in a rapid decrease of Candida CFU in the blood, liver, and spleen during the first 8 h, after which blood cultures were negative on day 2 and viable Candida burdens in the liver and spleen persisted at 10(5) CFU/g, whereas Candida mannan antigen continued to circulate in the bloodstream and accumulated in the liver and spleen.

Animals↗
PubMed1991

Gonadal development and growth in 46,XX and 46,XY individuals with P450scc deficiency (congenital lipoid adrenal hyperplasia).

We have investigated gonadal development and growth in 4 individuals (3 with 46,XY and 1 with 46,XX karyotype) with P450scc deficiency. One patient died at 2 months of age from adrenal insufficiency, while the remaining 3 individuals were healthy and developed normally (age at follow-up: 18, 10 and 8 years). In the surviving individuals, the diagnosis was established during the first 2-4 months of life by extensive endocrine studies of blood and urine. In the remaining patient, the diagnosis was made on the basis of karyotype (46,XY), anatomy of internal and external genitalia and adrenal pathology. Gonadectomy was performed in the 2 surviving 46,XY individuals at the age of 7 years, and histological examination showed normal testicular morphology but very few germ cells. Postmortem examination of the testes of the 2-month-old subject showed normal testicular histology, and quantitative analysis revealed a normal number of germ cells. Ultrasound of the 46,XX individual showed normal internal female genitalia including ovaries with follicles. The 3 surviving patients grew along the 75th (46,XY), the 90th (46,XY) and the 50th percentile (46,XX), respectively. The oldest girl experienced normal breast and pubic hair development after oral estrogen replacement and topical testosterone administration. The glucocorticoid and mineralocorticoid replacement was adjusted in accordance with repeated measurements of serum sodium and serum potassium, plasma renin concentration and blood pressure. No attempts were made to normalize serum ACTH. We conclude that prenatal testicular maturation and development of female internal genitalia may take place in the absence of normal steroid hormone production. Normal growth and development may be obtained in P450scc-deficient individuals with adequate hormone replacement.

Adolescent↗
PubMed1991

GH-replacement therapy in adults.

Growth hormone (GH) deficiency in adults, whether GH deficient since childhood or patients rendered GH deficient in adult life, is associated with psychosocial maladjustment, reduced muscle strength and reduced exercise capacity. Body composition is significantly altered with increased fat and decreased muscle volume as compared to healthy subjects. Kidney function is subnormal, and so is sweat secretion. Epidemiological data suggest premature mortality due to cardiovascular disease in hypopituitary patients. Short-term GH treatment trials have shown improved psychosocial performance, normalization of body composition, increased muscle strength, improved exercise capacity, increased cardiac performance and increase in bone mineral mass as well as in serum markers of bone turnover, and normalization of kidney function. Thus GH replacement therapy in GH-deficient adults exhibits potential long-term beneficial effects. A number of important questions has to be addressed before long-term GH replacement therapy in GH-deficient adults can be considered on a routine basis.

Adult↗
PubMed1991

Value of nuclear DNA ploidy patterns in patients with prostate cancer after radical prostatectomy.

Flow cytometric analysis of DNA ploidy was performed on prostatic adenocarcinoma specimens from 80 patients. In all these patients a radical retropubic prostatectomy had been performed. The nuclei for DNA ploidy determination were extracted from paraffin-embedded material of whole sections of the prostate from patients treated by radical prostatectomy between 1980 and 1985. DNA ploidy was a strong prognostic indicator independent of tumor grade and tumor stage. DNA ploidy offered additional information on both tumor stage and tumor grade. In stage C disease the likelihood of progression-free survival was 89.5% in diploid tumors and 27.8% in aneuploid tumors after 9 years. In tetraploid tumors all patients progressed after 9 years. The computed survival rates in stage C disease showed that patients with diploid tumors did significantly better than those with aneuploid or tetraploid tumor patterns. These data indicate therefore that DNA ploidy patterns determined by flow cytometric analysis provide important additional prognostic information on prostatic adenocarcinoma treated by radical prostatectomy.

Adenocarcinoma↗
PubMed1991

Target sequences for hunchback in a control region conferring Ultrabithorax expression boundaries.

Boundaries of Ultrabithorax expression are mediated by long-range repression acting through the PBX or ABX control region. We show here that either of these control regions confers an early band of beta-galactosidase expression which is restricted along the anteroposterior axis of the blastoderm embryo. This band is succeeded by a stripe pattern with very similar anteroposterior limits. Dissection of the PBX control region demonstrates that the two patterns are conferred by distinct cis-regulatory sequences contained within separate PBX subfragments. We find several binding sites for hunchback protein within both PBX subfragments. Zygotic hunchback function is required to prevent ectopic PBX expression. Moreover, the PBX pattern is completely suppressed in embryos containing uniformly distributed maternal hunchback protein. Our results strongly suggest that hunchback protein directly binds to the PBX control region and acts as a repressor to specify the boundary positions of the PBX pattern.

Animals↗
PubMed1991

Long-term growth hormone treatment in growth hormone deficient adults.

Growth hormone treatment in GH-deficient adults has proved beneficial in recent short-term trials, but long-term results have not yet been reported. Thirteen GH-deficient adults (4 females, 9 males; mean (SEM) age 26.4 (1.7) years), who had completed 4 months of GH therapy in a double-blind placebo-controlled cross-over study were followed, for further 16.1 (0.8) months of uninterrupted GH therapy in an open design. A significant mean increase of 1.3 cm in linear height was recorded, whereas body mass index remained unchanged. Mean muscle volume of the thigh, estimated by computerised tomography, increased significantly compared with that of the initial placebo period (p = 0.01), and a slight decrease was recorded in adipose tissue volume of the thigh (p = 0.10) and subscapular skinfold thickness (p = 0.10). Still, the muscle to fat ratio of the thigh was significantly lower compared with that of normal subjects (72.6/27.4 vs 77.9/22.1) (p less than 0.01). The mean isometric strength of the quadriceps muscles increased significantly during long-term GH therapy (p less than 0.01), but remained lower compared with that of normal subjects (1.66 (0.10) vs 2.13 (0.11) Nm/kg body weight). Exercise capacity performed on a bicycle ergometer increased significantly after long-term therapy (p less than 0.05), but still did not reach the values seen in normal subjects (22.5 (3.4) vs 37.4 (4.2) watt.min.kg-1. No adverse reactions were recorded during long-term therapy and hemoglobin A1c remained unchanged. These data suggest that long-term GH replacement therapy in GH-deficient adults has beneficial effects on several physiological features which are subnormal in these patients.

Adult↗
PubMed1991

[Inborn immunodeficiencies].

Primary immunodeficiency syndromes may be seen as "experiments of nature", giving insights into the organization and function of the human immune system. The principal categories of primary immunodeficiency syndromes: severe combined immunodeficiency, agammaglobulinemia and isolated T-cell defects (e.g. Di George Syndrome) are still used in view of their leading clinical presentations. However, detailed analysis of individual cases and families now shows a plethora of different diseases in each category. In this review the relationship of primary immunodeficiency diseases of the B-cell system and autoimmune phenomena are discussed. The pathology of thymus in severe combined immunodeficiency is shown: central maturation defects of the T-cell system are not due to "dysplasia" of the thymus but rather to enzyme defects of the lymphatic cells. Severe alterations of the thymus may also be caused by graft versus host disease. The clarification of genetic defects of lymphoid differentiation and maturation today may lead to improved early and prenatal diagnosis as well as specific gene therapy. The success of bone marrow transplantation in many cases of primary immunodeficiency disease syndromes may be considered as a consequence of successful gene therapy.

Humans↗
PubMed1991

[Polyvalent immunoglobulins in prevention of viral infections in children with neoplastic diseases treated with immunosuppressive therapy].

31 children with leukemias, lymphomas and solid tumors treated by polychemotherapy received prophylactic i.v. polyvalent immunoglobulins during 48 hours after exposion with varicella-zoster-virus, rubella-virus or mumps-virus. None of the 23 children with immunity against the exposed virus developed the infection. 8 children had no antibodies against the exposed virus. The prophylaxis with the polyvalent immunoglobulin protected them against chickenpox (6 children) and rubella (2 children). All children showed an elevation of the IgG level in plasma and the antibody titers against measles-, mumps-, rubella- and varicella-zoster-virus after application of the immunoglobulin. A study with a larger number of patients is necessary to confirm our results, that polyvalent immunoglobulins with high titers against exposed viruses are effective in prevention of this diseases in immunocompromised children.

Adolescent↗
PubMed1991

[In vitro culture of pulp cells].

The purpose of our study was the culture of cellular elements of the pulp. Migration and proliferation of fibroblast-like cells can be observed during the in vitro culture of pulpal tissue. However, no mitotic acticity of the odontoblasts could be induced by nutritive variations of the culture medium. The proliferation of the fibroblastlike cells varied during the primary culture and the first subculture. By contrast, during the second subculture there is a homogeneous process of growth. The growth rate of the second subcultures is therefore suitable for a biological evaluation of dental materials.

Animals↗
PubMed1991

[Recent evaluation of a Candida hemagglutination test].

The production of the Candida hemagglutination test Roche (C-HAT Roche) has been discontinued by the producer late in 1990. This deficiency is covered by the newly developed Candida hemagglutination test LD (C-HAT LD) (producer: Labordiagnostika Heiden/Westfalen). The test is performed on microtiter plates (V-shape, broadside). The necessary volume of probands' sera is 25 microliters. The range of the antibody titers to be determined ranks from 1:10 until 1:2500. In the evaluation of the C-HAT LD with reference sera compared with the C-HAT Roche the following results were obtained: The antibody titers determined by C-HAT LD differ at maximum by one titer step from those obtained by the C-HAT Roche and are, therefore, comparable. In the C-HAT LD the probands' sera are not preabsorbed with unloaded sheep erythrocytes in order to eliminate unspecific agglutinins. The hitherto existing experience shows that the proportion of probands' sera containing unspecific agglutinins is as low as 2.5%. The repetition of the C-HAT LD with such sera after preabsorption is, therefore, much more economical than generally preabsorbing all probands' sera. In 18% of all tests a prozone phenomenon is observed with the C-HAT LD. In the majority of these sera the titer steps 1:10 and 1:20 show negative reactions. The determination of the antibody titer, however, is not influenced by the prozone phenomenon. Preabsorption of probands' sera eliminates the prozone phenomenon. The C-HAT LD, therefore, replaces the C-HAT Roche completely in all parameters and is technically easier.

Animals↗