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Biomedical subjects

J Müller

Publications and source records attributed to J Müller.

At least 19 recordsLinked to original sources

[The solitary pulmonary histoplasmoma].

A 63-year-old man who grows orchids as a hobby, fell ill with weakness and pain in his hips and legs 2 months after his latest trip to South America (Ecuador). The WBC count was 9900/microliters with unremarkable differential count while blood sedimentation rate was raised to 60/100 mm. The chest X-ray demonstrated in the right upper lobe a well-circumscribed coin lesion (3 cm diameter) of soft-tissue density, uncalcified and without cavitation. Computed tomography in addition revealed an enlarged lymph-node at the lower hilar pole, but no mediastinal lymphoma. Bronchoscopy demonstrated narrowing of a subsegmental ostium of the 6th segment on the right. An attempt at transbronchial biopsy failed. As a peripheral bronchial carcinoma was suspected, a posterolateral thoracotomy was performed (4 months after the trip to Ecuador). Rapid histological examination was negative for tumour and the lesion was therefore enucleated. Histologically (Grocott silver staining) a histoplasmoma was diagnosed. Several serum samples were positive for precipitating (M-band) and complement-binding antibodies (titre 12 days preoperatively was 1:16). The postoperative course was without complication. No anti-histoplasma antibodies were demonstrable 1 year postoperatively.

Antibodies, Fungal

Synthesis and degradation of polyphosphate in the fission yeast Schizosaccharomyces pombe: mutations in phosphatase genes do not affect polyphosphate metabolism.

The fission yeast Schizosaccharomyces pombe was found to accumulate large amounts of polyphosphate, particularly when grown on arginine as the nitrogen source. Upon transfer to a medium without phosphate, polyphosphate was degraded and served as an endogenous phosphate reserve. When phosphate was added again after a prolonged period of phosphate starvation, fission yeast cells synthesized more polyphosphate than they had contained before starvation, a phenomenon known as over-compensation. Strains carrying mutated structural genes for three different phosphatases, pho1, pho2 or pho3, degraded polyphosphate at the same rate as the wild-type strain during phosphate starvation and showed the same type of over-compensation when phosphate was added again.

Genes, Fungal

[Addison's disease in the framework of poly-glandular autoimmune syndromes: 3 case reports].

Case reports of three patients with idiopathic Addison's disease combined with other associated autoimmune endocrine and non-endocrine disorders are presented. In the first patient, a young man with a long-standing history of mucocutaneous candidiasis, latent Addison's disease was discovered by diagnostic screening tests. In the two other patients, women aged 39 and 20 respectively, overt Addison's disease combined with primary hypothyroidism was diagnosed. One of them also had a pre-existing ovarian failure. The polyglandular autoimmune syndromes with Addison's disease are classified into two different subtypes, on the basis of characteristic patterns of disease combinations and on different modes of inheritance. Patients with autoimmune Addison's disease are at relatively high risk for other endocrine disorders or non-endocrine autoimmune diseases. Therefore, these patients--and in some instances also their relatives--need lifelong supervision and advice to ensure timely recognition of any associated diseases.

Addison Disease

[Taenia crassiceps infection in AIDS].

A 33-year-old patient with AIDS, and a history of episodes of Pneumocystis carinii pneumonia and cerebral toxoplasmosis, developed a subcutaneous paravertebral infiltrate, which at first resembled a haematoma. Over a period of several weeks, the lesion spread to cover almost the entire back. Initially, numerous investigations failed to reveal the aetiology. His general condition worsened progressively, and intermittent bleeding into the soft tissue of the back occurred, requiring transfusion. This was associated with the development of an isolated deficiency of clotting factor V and a fall in Quick values to 10%. On the 22nd day after admission, the infiltrate ruptured spontaneously, releasing blood and a large number of whitish spherical masses 2-3 mm in diameter. These were identified as Cysticerci longicolles, the larval form of Taenia crassiceps, a tapeworm occurring in Canidae. The blood clotting values returned to normal within two days of incision of the infiltrate and commencement of therapy with mebendazole (6 g/day) and praziquantel (3.6 g/day). The infiltrate subsequently regressed almost completely. After combination treatment for 2 weeks, treatment was continued with praziquantel alone, which, however, the patient stopped himself after 10 weeks. A recurrence at the same site 4 months later was successfully treated with a further course of mebendazole and praziquantel.

Acquired Immunodeficiency Syndrome

Assessment of oxidative DNA damage in the oxyR-deficient SOS chromotest strain Escherichia coli PQ300.

The SOS chromotest is a simple short-term genotoxicity assay measuring the induction of gene sfiA in Escherichia coli K-12. The recent availability of SOS tester strains with additional mutations in DNA repair or protection systems allows testing of DNA damaging compounds for genotoxic specificity. E. coli PQ300 differs from the standard SOS tester strain PQ37 in that it contains an additional mutation in gene oxyR that renders it more sensitive to oxidative genotoxins. The generation of reactive oxygen intermediates (ROI) by hydroperoxides (H2O2, t-butyl hydroperoxide, cumene hydroperoxide), gamma-radiation, glucose oxidase, and xanthine oxidase resulted in a more vigorous SOS response in strain PQ300 compared to strain PQ37. PQ300 was also more sensitive than PQ37 for the detection of reducing agents such as ascorbic acid, cysteine, and glutathione, which also alter the redox status of the bacterial cells. However, intercalating agents (adriamycin, bleomycin, and mitomycin C) and the UV- and radiomimetic compound 4-nitroquinoline-1-oxide whose DNA damaging potential are known also to involve ROI did not show significant differences between strains PQ37 and PQ300. It is concluded that the oxyR-deficient strain PQ300 is useful for detecting certain classes of genotoxins that change the oxidative/antioxidative balance of tester bacteria in the SOS chromotest.

DNA Damage

Sharp anterior boundary of homeotic gene expression conferred by the fushi tarazu protein.

Parasegmental boundaries in the Drosophila embryo are delimited by the products of the fushi tarazu (ftz) and even-skipped (eve) genes. We show here that these act through particular key control regions of the homeotic gene Ultrabithorax (Ubx) to generate ftz- or eve-like stripe patterns of beta-galactosidase expression. Footprint analysis and tests in transformed embryos of constructs bearing mutated footprint regions suggest that ftz protein acts directly as a transcriptional activator of Ubx. Its activity outside the Ubx expression domain is suppressed by hunchback (hb), a repressor of Ubx. Some DNA binding sites for ftz protein are adjacent to, others overlap binding sites for hb protein, and we provide evidence that ftz protein competes with hb protein for DNA binding and/or for transcriptional activation. This competition mechanism results in a sharp anterior expression boundary. Direct activation of homeotic gene control regions by ftz (or eve) protein may be a regulatory step which is generally used to align expression of homeotic genes with parasegmental boundaries.

Animals

Role of prostacyclin in normal and arteriosclerotic human coronary arteries during hypoxia.

Human coronary arteries were taken from heart transplant patients. Arteriosclerotic arteries were more depolarized and constricted over the whole PO2 range between 535 and 0 mm Hg. During oxygen deficiency, control preparations showed a maximal hyperpolarization of delta V = 10.9 mV and a maximal relaxation of delta T = 0.466 g. Arteriosclerotic arteries, however, became hyperpolarized by merely delta V = 7.1 mV and relaxed by delta T = 0.258 g. The isometric pretension was 2 g in all investigations. Two series of experiments, one with an application of indomethacin and another one with deendothelialized blood vessels, confirmed the hypothesis that the endothelium of arteriosclerotic coronary arteries arteries, indomethacin reduced the hypoxic hyperpolarization and dilatation at 30 mm Hg PO2 but about 51%. The reduction was 26% in arteriosclerotic vessels. The complete removal of the endothelium caused a 49% (74%) restriction of dilatory vascular reactivity. The relation was quite similar for a carbogen Krebs solution (resting, control conditions). The hyperpolarizing and dilatory contribution by prostacyclin was 32% in normal and 12% in arteriosclerotic coronaries. The rest can be attributed to the basal release of the endothelial dilator EDHR. Thus, it may be concluded that, in arteriosclerotic blood vessels, PGI2 synthesis and release are predominantly diminished or its effectivity is impaired. Finally we found the ratio PGI2/EDHF in the voltage and tension changes strongly shifted to the PGI2 side with a declining oxygen concentration. This is true for normal and arteriosclerotic vessels. In accordance with the activation curve for vascular smooth muscle, the hyperpolarization leads to relaxation via a closure of Ca2+ channels. 2.5 mV hyperpolarization reduces the tension developed by half.

Arteriosclerosis

Urinary free cortisol versus 17-hydroxycorticosteroids: a comparative study of their diagnostic value in Cushing's syndrome.

We evaluated the usefulness of the basal urinary 24-h excretion rates of free cortisol versus 17-hydroxycorticosteroids in the diagnosis of Cushing's syndrome. On an outpatient basis, both urinary free cortisol and 17-hydroxycorticosteroids levels were determined in 48 patients with Cushing's syndrome, as well as in 95 obese and 94 healthy control persons of normal weight. Determination of the urinary free cortisol content allowed a clear-cut distinction between the patients with hypercortisolism and the controls, resulting in a sensitivity of 100% and specificity of 98% for the diagnosis of Cushing's syndrome. The diagnostic accuracy of urinary free cortisol was distinctly superior to that of 17-hydroxycorticosteroids, which showed a wide overlap of values between the groups, with a sensitivity of 73% and a specificity of 94%. In conclusion, the measurement of basal urinary free cortisol provided an excellent diagnostic sensitivity and specificity in the assessment of adrenocortical function. This simple and accurate test thus seems to be particularly useful in the outpatient evaluation of patients with suspected Cushing's syndrome.

17-Hydroxycorticosteroids

Suppression of the growth and export defects of an Escherichia coli secA(Ts) mutant by a gene cloned from Bacillus subtilis.

A gene library of Bacillus subtilis chromosomal DNA was screened for genes capable of reverting the growth defects of the Escherichia coli secA51(Ts) mutant at 42 degrees C. A B. subtilis gene, designated csaA, was found to phenotypically suppress not only the growth defects of the E. coli mutant, but also to relieve the detrimental accumulation of precursors of exported proteins. The csaA gene encoded a protein of 15 kDa (137 amino acids) and was likely to be the distalmost member of an operon. No similarity to csaA was found among DNA or protein sequences deposited in databases. In contrast to other homologous or heterologous suppressors of the E. coli secA51(Ts) mutation, the csaA gene did not exert pleiotropic effects on either the E. coli secY24(Ts) or lep9(Ts) mutations. However, it restored the ability of a SecB-deficient mutant to grow on complex medium. It is proposed that CsaA serves as a molecular chaperone for exported proteins or alternatively acts by stabilizing the SecA protein.

Adenosine Triphosphatases

Transport and in vivo elimination of cysteinyl leukotrienes.

Transport processes control not only synthesis and release of LTC4 but also the elimination and excretion of LTC4 and its metabolites. (i) A primary-active ATP-dependent export carrier mediates the release of LTC4 from a leukotriene-generating cell, as exemplified by mastocytoma cells, and as measured in mastocytoma plasma membrane vesicles (2). (ii) Release of cysteinyl leukotrienes into the blood circulation is followed by a rapid elimination with an initial half-life of 38 sec in rats and 4.0 min in man, as measured with the labeled, representative LTC4 catabolite, N-acetyl-LTE4. (iii) 11C-labeled N-acetyl-LTE4 can serve for non-invasive studies on cysteinyl leukotriene elimination and excretion by the liver and kidney in the intact organism using positron emission tomography. An impairment of leukotriene transport from the liver across the canalicular membrane into bile, studied in mutant rats and in extrahepatic cholestasis, leads to a compensatory diversion of cysteinyl leukotriene elimination to the kidney. N-Acetyl-LTE4 labeled with a short-lived positron-emitting isotope provides quantitative insight into the pathways of cysteinyl leukotriene elimination in vivo. (iv) Cysteinyl leukotriene export from the liver into bile is mediated by an ATP-dependent primary-active export carrier. This decisive step in cysteinyl leukotriene elimination has been characterized in hepatocyte canalicular membrane vesicles (3). The leukotriene exporter is deficient in transport mutant rats. The leukotriene carrier is distinct from other ATP-dependent export carriers identified in this membrane domain, such as the ATP-dependent bile salt export carrier (25) and the multidrug export carrier (27).

Adenosine Triphosphate

[Piriform sinus fistulas as rare hypopharyngeal abnormalities, diagnosis and therapy].

We report on the history, clinical findings, diagnostic examinations and the therapy of three patients with a left piriform sinus fistula, probably a fourth pharyngeal pouch. Our patients show recurrent inflammation and abscesses of the left lateral neck. X-ray (gastrografin swallow) showed the fistula originating from the floor of the left piriform sinus. CT-scan was helpful in the previously operated area, although the fistula could be shown by ultrasonic examination. Recurrent abscesses of the lateral neck may be caused by sinus piriform fistula. It is important to search for this rare malformation of the lateral neck.

Abscess

Influence of amorolfine on the morphology of Candida albicans and Trichophyton mentagrophytes.

Amorolfine applied in concentrations of 0.1-100 micrograms/ml causes considerable damage to the ultrastructure of Candida albicans and Trichophyton mentagrophytes: electron-lucent areas appear in the cytoplasm; extracytoplasmic membrane vesicles are formed and deposited in the cell wall; starved fungal cells, with normal ultrastructure, can be found; lysed, dead cells demonstrate the process of severe ultrastructural damage; T. mentagrophytes cell walls especially increase in thickness. The extent of the damage caused by amorolfine is comparable to that produced by azole antifungals.

Candida albicans

Hormonal treatment of cryptorchidism--hCG or GnRH--a multicentre study.

In a modified, double-blind controlled study, 163 prepubertal boys (aged 1.8-13.0 years) with bilateral and 94 (aged 1.5-13.1 years) with unilateral cryptorchidism were allocated to treatment with either human chorionic gonadotrophin (im), gonadotrophin releasing hormone (intranasally) or placebo (intranasally). In individuals with the bilateral condition treatment with human chorionic gonadotrophin resulted in complete descent of both testes in 23% of patients. Treatment with human chorionic gonadotrophin in unilateral cryptorchidism resulted in complete descent in 19% of patients; all results were significantly better than those obtained with gonadotrophin releasing hormone or placebo. Linear and logistic regression analysis of the results obtained by treatment of bilateral disease showed that all treatments were more successful the younger the age of the boys. The data indicated that bilateral and unilateral cryptorchidism respond differently to hormonal treatment. We suggest that human chorionic gonadotrophin should be the first choice of treatment for prepubertal boys older than one year.

Administration, Intranasal

Carcinoma in situ, gonadoblastoma, and early invasive neoplasia in a nine-year-old girl with 46,XY gonadal dysgenesis.

Carcinoma in situ (CIS), gonadoblastoma, and early invasive neoplasia were detected in the dysgenetic gonad of a nine-year-old girl with 46,XY gonadal dysgenesis. A close relationship between the three neoplastic components was supported by morphological and immunohistochemical studies. Our findings support the hypothesis that all germ cell tumours, including gonadoblastomas, originate from CIS germ cells formed during early embryonic life.

Carcinoma in Situ

Standardized susceptibility testing of fluconazole: an international collaborative study.

An international collaborative study of broth dilution (MIC) and disk diffusion susceptibility testing of fluconazole was conducted by using a chemically defined medium (High-Resolution Antifungal Assay Medium; Oxoid Ltd., Basingstoke, United Kingdom) and standard test methods performed in eight reference laboratories. Ten yeast isolates were tested by each test method in duplicate on each of 3 separate days. The intralaboratory reproducibility of the MIC test was excellent; 95.7% of the replicate tests (n = 220) were within 2 doubling dilutions of the other values in the set for the eight laboratories. The intralaboratory reproducibility of the disk test was also good, with 91% of the replicate tests (n = 234) agreeing with each other within an arbitrarily chosen value of 4 mm. Interlaboratory agreement of MIC test results was acceptable, with 84% of the MICs agreeing within 2 doubling dilutions. In contrast, the interlaboratory agreement of the disk test was not good, with only 59% of test results agreeing within 4 mm. Comparison of the rank order of MICs obtained in each laboratory with the reference rank order gave an agreement of 70 to 80% (median, 80%) with the MIC test and 70 to 90% (median, 80%) with the disk test. These preliminary results are encouraging for the development of standardized testing methods for testing fluconazole.

Culture Media

Influence of amorolfine on the morphology of Candida albicans and Trichophyton mentagrophytes.

Amorolfine applied in concentrations of 0.1-100 micrograms/ml causes considerable damage to the ultrastructure of Candida albicans and Trichophyton mentagrophytes: electron-lucent areas appear in the cytoplasm. Extracytoplasmic membrane vesicles are formed and deposited in the cell wall. Starved fungal cells, with normal ultrastructure, can be found. Lysed, dead cells demonstrate the process of severe ultrastructural damage. T. mentagrophytes cell walls especially increase in thickness. The feature of the damage caused by amorolfine is comparable to that produced by azole antifungals.

Antifungal Agents