Intronic <Emphasis Type="Italic">TP53</Emphasis> Germline Sequence Variants Modify the Risk in German Breast/Ovarian Cancer Families

To establish the contribution of TP53 germline mutations to familial breast/ovarian cancer in Germany we screened the complete coding region of the TP53 gene in a series of German breast/ovarian cancer families negative for mutations in the BRCA1 and BRCA2 genes.Two different intronic TP53 sequence variants were identified in 6/48 (12.5%) breast/ovarian cancer families. A novel A to T nucleotide change at position 17708 in intron 10 segregating with the disease was detected in three breast cancer families (6.2%). One 17708 A>T-associated breast tumour showed loss of the wild-type allele. This variant was also found in 5/112 (4.5%) healthy controls indicating that it is a polymorphism. A second sequence variant changing a G to C at position 13964 in intron 6 not segregating with the disease was found in two breast cancer families and one breast-ovarian cancer family (6.2%). This variant has previously been shown to occur at an elevated frequency in hereditary breast cancer patients from North America and to be of functional importance leading to inhibition of apoptosis and prolongation of cell survival after DNA-damage. Screening of 185 consecutive unselected German breast cancer patients revealed the 13964 G>C variant in four patients (2.2%). Immunohistochemical analysis of the TP53 protein showed negative immunoreactivity in normal and tumour tissues of one 17708 A>T and six 13964 G>C carriers. TP53 overexpression was detected in the tumour tissue of one sporadic breast cancer patient carrying the 13964 G>C variant. Our results show that intronic changes of the TP53 gene may act as or be associated with risk modifiers in familial breast cancer.     

Tropical spastic paraparesis: A model of virus-induced,cytotoxic T-cell–mediated demyelination?

Tropical spastic paraparesis is a neurological disorder that is most commonly seen in certain tropical (mainly Caribbean) areas and that presents as a progressive spastic paraparesis and urinary dysfunction. Recent studies have revealed an association between tropical spastic paraparesis and human T-cell lymphotropic virus type I (HTLV-I) infection. We report the results of a detailed morphological and immunocytochemical study of a patient with tropical spastic paraparesis. Lesions were restricted to the spinal cord and optic nerve, where demyelination, inflammation, and fiber loss were common features. Lymphocytes were seen closely applied to nerve fibers within which were changes resembling those seen in myelinated central nervous system cultures exposed to cytokines. Immunocyctochemically, HTLV-I p19 core protein and a predominance of CD8+ (suppressor/cytotoxic) T cells and expression of class I major histocompatibility antigen were demonstrated in spinal cord lesions. It is postulated that cytotoxic T cells, either directly or via cytokines, induce lysis of the myelin sheath and subsequently the axon, resulting in a mixed picture of demyelination and axonal loss with secondary tractal degeneration. Despite this destruction, extensive remyelination was evident within affected areas of spinal cord.     

DNA measurements and ploidy determination of different stages in the life cycle ofSarcocystis muris

The DNA contents of different stages within the life cycle ofSarcocystis muris were measured cytophotometrically using DNA-specific Feulgen staining. Stages of gamogony were obtained by the transfer of isolated cyst merozoites into cat kidney-cell cultures. For calculation of absolute DNA contents, the amounts of DNA in the parasites were compared with those in chicken erythrocytes, which are known. The measurements revealed that all investigated stages ofS. muris contained haploid DNA except the early zygotes, which were diploid. The further development of the zygotes started with a nuclear division, resulting in two daughter nuclei that again revealed haploid DNA values. The results confirm the existence of zygotic meiosis; thus, a haplo-homophasic life cycle is proposed for the Sarcosporidia.Dedicated to Prof. Dr. G. Piekarski on the occasion of his 80th anniversary (October 5, 1990)Supported by the Deutsche Forschungsgemeinschaft (DFG)     

Metabolism of PAH by fungi and correlation with extracellular enzymatic activities

The activity to metabolize the polycyclic aromatic hydrocarbons (PAH) phenanthrene, anthracene, pyrene, fluorene and fluoranthene by Trametes versicolor, Pleurotus ostreatus (white rot fungi), Laetiporus sulphureus, Daedaela quercina, Flamulina velutipes (brown rot fungi), Marasmiellus sp. (litter decaying fungus) and Penicillium sp. M 1 (isolated from a PAH contaminated soil sample) were compared. Screening methods for the presence of exoenzymes (peroxidases, polyphenoloxidases, “radical generating” enzymes) were evaluated for their use in screenings for fungi degrading PAH. Laetiporus sulphureus and Penicillium sp. M 1 cometabolize several PAH with rates comparable to white rot fungi. In most of the cases the patterns of extracellular peroxidases indicate the potential of fungi to degrade PAH.     

Comparative studies on keratinase production of Trichophyton mentagrophytes strains of animal origin

Summary. Over a period of 28 days, 10 Trichophyton mentagrophytes strains were examined for their ability to secrete keratinolytic enzymes. Production of enzymes was stimulated by various keratins used as substrates. Duration and intensity of keratinase secretion were strongly influenced by the keratinous substrate. Duration and intensity of the enzyme production also differed among the 10 dermatophyte strains. Five different enzymes were isolated with molecular weights ranging from 28 kDa to 65 kDa. The different enzymes might be produced by different varieties of the species Trichophyton mentagrophytes.
Zusammenfassung. Über einen Zeitraum von 28 Tagen wurden 10 Trichophyton mentagrophytes -Stämme hinsichtlich ihrer Föhigkeit zur Sekretion keratinolytischer Enzyme untersucht. Die Keratinasebildung wurde durch verschiedene als Substrat verwendete Keratine stimuliert. Die Stärke und Dauer der Keratinasesekretion wurde sowohl von den verwendeten, Substraten als auch von den verschiedenen, untersuchten Stämmen beeinflußt. Es konnten 5 verschiedene Keratinasen mit Molekulargewichten zwischen 28 kDa und 65 kDa isoliert werden. Die Bildung verschiedener Keratinasen ist möglicherweise durch die Zugehörigkeit der Hautpilze zu verschiedenen Varietäten der Spezies Trichophyton mentagrophytes bedingt.     

Quantification of the Effect of Inhaled Budesonide on Airway Inflammation in Intermittent Asthma by Bronchitis Index

The bronchitis index (BI) is a scoring system for the visual quantification of airway inflammation by flexible bronchoscopy. A prospective study was carried out to determine whether patients with intermittent asthma present a considerable visible airway inflammation. Ten steroid-naive patients with intermittent asthma taking only inhaled β₂-agonists were enrolled and received budesonide (800 μg/day) over a period of 4 weeks. The airway inflammation was assessed by flexible electronic videobronchoscopy before and after the steroid treatment phase and quantified using the BI. Despite normal pulmonary function, all patients with intermittent asthma showed a marked visible airway inflammation that was reversed by a 4-week treatment with the inhaled steroid budesonide. The present study demonstrates that the BI may be useful as a clinical research tool for the assessment and quantification of airway inflammation in asthma. Furthermore, our results support the widely recognized theory that airway inflammation is present even in patients with mild asthma, and emphasize the necessity of an early therapy with inhaled steroids.     

Unusual location of a posttraumatic ganglion and rupture of the peroneus brevis tendon: A case report

The typical location of a peroneus brevis tendon tear has been described at the posterior margin of the fibula due to an entrapment mechanism or repetitive anterior subluxation of the tendon. A case of a posttraumatic intratendinous ganglion of the peroneus brevis tendon in the distal third of the peroneus brevis is reported. The ganglion developed from a longitudinal tear in the tendon substance after an inversion ankle sprain. This case is reported because of the unusual location. The clinical course and surgical treatment is also discussed.     

Expression of cyclooxygenase-1 and cyclooxygenase-2 in human renal allograft rejection – a prospective study

Cyclooxygenases (COX) are known to be involved in inflammatory kidney diseases. However, there are no data available about the expression of COX-1 and only preliminary reports about the expression of COX-2 in biopsies of patients undergoing acute renal allograft rejection. We conducted this prospective study to analyze the expression, distribution, and cellular localization of COX-1 and -2 and thus to elucidate the role of COX in human kidney transplantation. One hundred forty-four biopsies were included from patients without rejection and unaltered morphology (n = 60), with acute interstitial rejection (n = 7), with acute vascular rejection (n = 21), with chronic allograft nephropathy (n = 16), without rejection but with various other lesions (n = 40). COX-1 and -2 expression was localized in each biopsy by immunohistochemistry. We found a highly significant up-regulation of COX-1 in vessels and in infiltrating interstitial cells of patients with acute allograft rejection compared with biopsies with well-preserved tissue. Also, COX-2 expression was significantly elevated in infiltrating interstitial cells of biopsies with acute rejection. This is the first prospective study demonstrating a significant induction of both COX-1 and -2 in human allograft biopsies with acute rejection after renal transplantation.