Differentially expressed genes associated with tryptophan-dependent pigment synthesis in Malassezia furfur--a comparison with the recently published genome of Malassezia globosa.

Malassezia (M.) furfur, a commensal organism found on the human skin, produces a wide range of pigments and fluorochromes when cultured with tryptophan as a sole nitrogen source. Some compounds of this pigment metabolism may provide an explanation for clinical characteristics of pityriasis versicolor (PV), a frequent skin disease in humans characterised by long-lasting pigmentary changes. Malassezia globosa is currently regarded as the causative agent of PV, but tryptophan-dependent pigment production has not yet been demonstrated in this species. In a previous study, we identified M. furfur genes that were differentially expressed 3 and 5 h, respectively, after induction of tryptophan-dependent pigment production. The recent publication of the genome of M. globosa prompted us to check the M. furfur sequences for homologues in M. globosa. The 3-h pool contained 79 sequences and the 5-h pool contained 91 sequences. A translated vs. translated BLAST search resulted in 62 sequences (78%) of the 3-h pool and 61 sequences (67%) of the 5-h pool showing similarity to a sequence from M. globosa. It appears that M. globosa possesses homologues to most of the genes that are differentially expressed during pigment production in M. furfur.

Analysis of differentially expressed genes associated with tryptophan-dependent pigment synthesis in M. furfur by cDNA subtraction technology.

Malassezia species are associated with pityriasis versicolor (PV) and its depigmented variant pityriasis versicolor alba (PVa), widespread fungal skin infections in humans. The pathogenesis of PV and PVa remains unclear, including their clinical and histological symptoms such as hyper- and depigmentation, reduced responsiveness to ultraviolet radiation and lack of inflammatory reaction despite high fungal load. Pigments produced by M. furfur are possibly involved in the pathogenesis of PV. In vitro, M. furfur produces a wide range of pigments and fluorochromes when cultured with tryptophan as the sole nitrogen source. We have begun to analyse the molecular basis of pigment production by searching for genes associated with tryptophan-based pigment production. A suppression subtractive hybridization (SSH) protocol was used to identify genes expressed in M. furfur cells producing pigments, but not in non-induced cells. SSH was performed 3 and 5 h after onset of pigment induction. Up-regulation of genes in the pigment-producing cells was confirmed by reverse northern analysis. More than 1,500 cDNA sequences of both the indicated time points were analysed. We identified a wide variety of genes associated with metabolism and several genes with unknown function are specifically expressed during pigment production. Furthermore, a fraction of genes possibly involved in different steps of the newly discovered indolic pathway of M. furfur were expressed in pigment producing cells. These data provide the first molecular insight into pigment production of M. furfur.

Ultrastructural findings in endomyocardial biopsy of patients with Kearns-Sayre syndrome.

Kearns-Sayre syndrome is clinically defined by progressive external ophthalmoplegia, atypical retinitis pigmentosa and the potential occurrence of complete atrioventricular (AV) block. Right septal endomyocardial biopsy specimens from nine patients (four men and five women with a mean [+/- SD] [corrected] age of 36.3 +/- 14.4 years) with chronic progressive external ophthalmoplegia and mitochondrial skeletal myopathy were studied. Three patients had atypical retinal pigmentation. An atrioventricular or intraventricular conduction defect was observed in five patients. A pacemaker was prophylactically implanted in one patient because of abnormal conduction distal to the His bundle. Ultrastructural investigations revealed mitochondriosis in many heart muscle cells and an increased variability of mitochondrial form and size in all patients. In seven patients, 0.4 to 2.1% of all examined myocytes contained exclusively abnormal mitochondria. Three main types were observed: huge, mainly round mitochondria with concentric cristae; large, round or oval mitochondria with transverse or curved cristae; and small, vacuolated mitochondria. The volume density of myofibrils was reduced (41.9 +/- 11.1 compared with the normal value of 56.5 +/- 2.5 volume density [in percent], p less than 0.01) in these myocytes. Increasing numbers of vacuolated mitochondria correlated significantly with a reduction of myofibrils (r = -0.64, p less than 0.01). The data suggest that the ventricular myocardium of most patients with complete and even incomplete Kearns-Sayre syndrome is affected by disseminated mitochondrial cytopathy.

No effect of saphenous intimal thickness on patency of aorta-coronary bypass grafts.

Forty-two of 261 aorta-coronary saphenous vein bypass grafts had closed by 8 +/- 7 months postoperatively. The average preoperative intimal thickness of the nonpatent bypass grafts (158 +/- 132 microns) was nearly identical to that of the patent grafts (160 +/- 133 microns).

Cardiac amyloid deposits in endomyocardial biopsies. Light microscopic, ultrastructural, and immunohistochemical studies.

In four patients with unexplained, abnormal thickening of the interventricular septum as demonstrated by echocardiography, right ventricular endomyocardial biopsy revealed unexpected cardiac amyloid deposits that resulted in increased myocardial thickness and rapidly progressive heart failure. Light microscopically, amyloid was observed in the subendocardial layer, interstitium, and walls of the intramural arterioles. Electron-microscopically, the amyloid fibrils were adjacent to the basement membranes of the heart muscle cells and the vascular smooth muscle cells. Immunohistochemical typing with specific antibodies against different amyloid fibril proteins on glutaraldehyde-fixed paraffin sections revealed different amyloid types. In two patients with generalized idiopathic amyloidosis and in two others with amyloidosis in multiple myeloma, the A-lambda form was diagnosed. In a fifth patient, AA-amyloidosis was found in familial Mediterranean fever with cardiac manifestation without thickening of the interventricular septum. The amyloid deposits were located almost exclusively within the walls of the myocardial arterioles. The amount of amyloid as observed in the myocardial biopsies correlates with the rapidly progressive cardiac failure. It is suggested that in patients with abnormal thickening of the interventricular septum of unknown origin the diagnosis should be clarified by endomyocardial biopsy.

Differentiated DNA analysis in relation to steroid receptor status, grading, and staging in human breast cancer.

Flow cytometric DNA analysis was performed in 100 cases of human breast cancer. Using a category system of six ploidy groups, ploidy status was distributed as follows: The majority of the neoplasias were either diploid (45%), hyperdiploid (21%), or tetraploid (15%), whereas the remaining marginal ploidy groups, i.e. hypodiploid (4%), hypertetraploid (9%), and multiploid (6%) were less frequent. In an attempt to evaluate the prognostic significance of DNA content, ploidy status was correlated with steroid hormone receptor status, histopathological grade, and TNM data. The higher incidence of negative estrogen and progestin receptor status and higher histopathological grade in hyperdiploid malignancies was significantly different from the prognostically more favorable positive receptor status and lower grade in diploid tumors. Tetraploid neoplasias statistically resembled the latter group with respect to both parameters. As far as TNM data are concerned, tendencies towards less favorable staging were observed in hyperdiploid as compared to diploid and tetraploid tumors. A definite statement of the prognostic significance of the marginal ploidy groups cannot be made at present. In order to characterize diploid malignancies more closely, proliferative activity expressed by %S-phase was analyzed. Steroid receptor status of diploid tumors exhibiting more than 6% S-phase did not differ statistically from that of hyperdiploid neoplasias. In contrast, diploid tumors expressing less than 6% S-phase closely resembled tetraploid ones. Our data emphasize the prognostic significance of differentiated DNA analysis.

[Morphology of myocardial perfusion (author's transl)]. / Morphologische Gesichtspunkte zur Myokardperfusion.

Disturbances of myocardial perfusion are mostly due to obstructive coronary atherosclerosis. The shape of the narrowed lumen is polymorphic. The localization of severe stenoses is not influenced by risk factors. Atherosclerotic changes are more frequent in the coronary arteries than in their large branches. There is a good agreement between the localization and the size of the infarct and the poststenotic or postocclusive perfusion area. As a rule there are only few atherosclerotic lesions within samll intramural arteries and arterioles of the myocardium. We could not find a positive correlation between the extent of sclerotic changes in large coronary arteries and arterioles.

[Differential diagnosis and prognosis of primary and post-myocarditis cardiomyopathy in childhood]. / Zur Differentialdiagnose und Prognose der primären und postmyokarditischen Kardiomyopathie im Kindesalter.

It is still difficult to differentiate between the various stages of myocarditis and primary dilated cardiomyopathy (DCM). Hence, we analyzed the history, as well as the laboratory and virological data of 22 children with a dilated, poorly functioning left ventricle, aged 2 months to 16.7 years (m = 4.2 y), on whom we had performed endomyocardial biopsies about 4 months after the beginning of the illness. Specimens were investigated by light and electron microscopy and, in addition immunoserological (n = 15) and immunohistological investigations (n = 7) were performed. On the basis of cellular infiltration in the histological examination we diagnosed resolving/resolved myocarditis in 6 patients and DCM in 15 patients. Previous respiratory infection or sudden onset were found in 40-50% of patients in both groups. Antimyolemmal and antisarcolemmal antibodies showed no preference. Follow-up (3.1 +/- 2.8 years) of the patients showed equal mortality (33% vs. 38%) in the post-myocarditis and DCM group. Complete normalization of all findings in 3 patients of the DCM group makes the classification among the post-myocarditis group probable, which would, then give a lower mortality rate (22% vs. 46%) and a chance of restitution in 55% of cases. In any one specific case all the diagnostic methods do not allow undoubted distinction between both entities. The prognosis of myocarditis seems to be better than that of DCM in childhood.

[Secondary diseases of the heart muscle and their differential diagnosis in childhood]. / Sekundäre Herzmuskelerkrankungen und ihre Differentialdiagnose im Kindesalter.

Possible causes of specific cardiac muscle disease, diagnosis, follow-up and the therapeutic management are discussed on the basis of a series of cases. 8 out of 30 patients who showed the clinical picture of dilative cardiomyopathy (DCM) were found to have a specific cardiac muscle disease. 4 patients had DCM following adriamycin therapy. Fibromuscular dysplasia with renal hypertension, thalassaemia major with secondary haemosiderosis, long-overlooked and untreated athyroidism each caused one case of dilative specific cardiac muscle disease. Once DCM was preceded by the Kawasaki syndrome for over 2 years. Amongst 47 patients with hypertrophic cardiomyopathy there were two children who had undergone ACTH treatment, 6 children born of diabetic mothers, 4 cases of Pompe's disease, and one patient with hypothyroidism resulting in reversible hypertrophy of the cardiac muscle. Different neurodegenerative diseases were associated with cardiac muscle disease in 4 cases, partly dictating the clinical course. Extremely rare was the development over 6 years of cardiac hypertrophy following a burns injury.

Impact of school and vocational education on smoking behaviour: results from a large-scale study on adolescents and young adults in Germany.

While level of school education has been related to prevalence of cigarette smoking in a number of studies, less information is available on the role of vocational education and related occupational contexts. This study analyses the relative contribution of different types of educational experience to explaining prevalence and intensity of cigarette smoking in a large sample of female and male vocational trainees in Germany. A standardized questionnaire on smoking behaviour and educational performance was applied in 27 educational centers across the country, covering a total of 20,527 respondents (77.3% of the original sample; women: 59.5%, men: 40.5%). Bivariate analysis revealed a high prevalence of current smokers among vocational trainees, both men (51.2%) and women (49.4%). Men were more likely to be heavy smokers, especially with increasing age. In both sexes, prevalence of smoking was particularly high in the following occupational groups: hairdressers, butchers, painters, service personnel (hotels, restaurants), shop assistants/sellers and cooks. Multivariate analysis taking educational level, type of vocational training (occupation), age, sex and urban-rural background into account revealed the highest prevalence odds ratios (POR) of smoking in subjects with the lowest educational level (POR = 5.19 for men and 4.56 for women). Even stronger effects were observed with smoking intensity (> or = 20 cigarettes/day): in men with the lowest educational level the risk of being a heavy smoker was 8.92, and in women 13.54 compared to subjects with a high-school leaving qualification. Poor school education must be considered the relatively strongest predictor of prevalence and intensity of cigarette smoking in a large sample of female and male vocational trainees. Preventive efforts should be directed at specific target groups such as those identified by this study.

[Arteriosclerotic plaque rupture. Its significance for myocardial infarct, sudden heart death and unstable angina]. / Der arteriosklerotische Polsterriss. Seine Bedeutung für den Herzinfarkt, den plötzlichen Herztod und die instabile Angina.

In coronary heart disease ruptures of atherosclerotic plaques have a key position. As a rule plaque fissuring develops in the fibrous cap of a complex atherosclerotic plaque with necrotic core. In myocardial infarction in nearly all cases mural or occlusive thrombi develop as a consequence of plaque ruptures. In instable angina, too, plaques with ruptured surfaces are very numerous but often thrombi are smaller than in patients dying from myocardial infarction. Also in cases of sudden death plaque fissurings are frequently observed. Dynamic thrombi covering plaque ruptures may be sources of microemboli in the myocardium.

[Malassezia yeasts and their significance in dermatology]. / Malassezia-Hefen und ihre Bedeutung in der Dermatologie.

Yeasts of the genus Malassezia belong to the normal microflora of the human skin. In addition they are known to cause a variety of skin diseases; the most frequent of which is pityriasis versicolor. Malassezia yeasts are also thought to be associated with seborrheic dermatitis, dandruff and Malassezia folliculitis. Recently the significance of Malassezia yeasts as a trigger factor for atopic dermatitis of the head and neck region has been pointed out. The role of the Malassezia yeasts in these different diseases has been controversial in the past and remains an issue because of difficulties in isolation, culture and differentiation of the organism. Thanks to molecular techniques, 10 species can actually be differentiated. The article presents the different Malassezia-associated diseases, their clinical picture, diagnosis and appropriate therapy. In addition the speciation of Malassezia is reviewed.

[Mycotic infections of the anogenital region]. / Anogenitale Pilzerkrankungen.

Mycotic infections of the anogenital region are very common in dermatological practice. While dermatophyte infections are more frequent in men, genital candidosis is a more striking problem in women. The increasing prevalence of non-albicans species (esp. C. glabrata, C. krusei, C. guilliermondii) with their resistance against azole derivatives may be responsible for therapeutic failures and a relapsing course in some instances. Most superficial infections of the anogenital area respond satisfactorily to topical antifungal treatment, especially if provocative factors and the possibility of sexual transmission are considered. Systemic treatment is recommended in cases of widespread dermatophyte infections, candidosis or systemic mycosis.

["The fungal jungle". Medical mycology on the Internet]. / "The fungal jungle". Medizinische Mykologie im Internet.

The World Wide Web offers an enormous variety of information about medical mycology. To go through the "fungal jungle" and find the website containing the information that is needed requires a great deal of effort and a lot of time. This article provides help in finding information about medical mycology and describes the contents of preselected websites in German and English. These pages address physicians, scientists, and students interested in dermato-mycology. Most of the pages also contain information about mycoses relevant to other medical specialties.