Streptococcal M1 protein constructs a pathological host fibrinogen network

M1 protein, a major virulence factor of the leading invasive strain of group A Streptococcus, is sufficient to induce toxic-shock-like vascular leakage and tissue injury. These events are triggered by the formation of a complex between M1 and fibrinogen that, unlike M1 or fibrinogen alone, leads to neutrophil activation. Here we provide a structural explanation for the pathological properties of the complex formed between streptococcal M1 and human fibrinogen. A conformationally dynamic coiled-coil dimer of M1 was found to organize four fibrinogen molecules into a specific cross-like pattern. This pattern supported the construction of a supramolecular network that was required for neutrophil activation but was distinct from a fibrin clot. Disruption of this network into other supramolecular assemblies was not tolerated. These results have bearing on the pathophysiology of streptococcal toxic shock.     

Effect of cadmium chloride on steroidogenic enzymes in the Bidder's organ of the toad (Bufo melanostictus)

Injection of cadmium chloride in a toad increases both the delta 5-3 beta-hydroxy-steroid dehydrogenase and 17 beta-hydroxysteroid dehydrogenase activities in Bidder's organ.     

The multifaceted Paneth cell

Paneth cells (PCs) were described over a century ago as granulated cells located at the base of small intestinal crypts, the 'crypts of Lieberkühn.' Various histochemical staining procedures were developed that identified PCs based on their distinctive granule staining pattern. Early on, PCs were proposed to perform a specialized function other than absorption of digested nutrients, the predominant task of the small intestinal epithelium. Since then, many constituents of the PC granules have been biochemically characterized. The presence of various granule-associated antimicrobial substances and their release upon microbial challenge suggest that PCs function as specialized defense cells in the small intestine. Altered resistance to microbial infection in animal models with disrupted or augmented PC function provides further support for the host defense role of PCs. Other PC components suggest that PCs may also participate in the regulation of lumenal ionic composition, crypt development, digestion, and intestinal inflammation. Received 6 June 2001; received after revision 26 July 2001; accepted 27 July 2001     

Delineation of prognostic biomarkers in prostate cancer

Prostate cancer is the most frequently diagnosed cancer in American men. Screening for prostate-specific antigen (PSA) has led to earlier detection of prostate cancer, but elevated serum PSA levels may be present in non-malignant conditions such as benign prostatic hyperlasia (BPH). Characterization of gene-expression profiles that molecularly distinguish prostatic neoplasms may identify genes involved in prostate carcinogenesis, elucidate clinical biomarkers, and lead to an improved classification of prostate cancer. Using microarrays of complementary DNA, we examined gene-expression profiles of more than 50 normal and neoplastic prostate specimens and three common prostate-cancer cell lines. Signature expression profiles of normal adjacent prostate (NAP), BPH, localized prostate cancer, and metastatic, hormone-refractory prostate cancer were determined. Here we establish many associations between genes and prostate cancer. We assessed two of these genes-hepsin, a transmembrane serine protease, and pim-1, a serine/threonine kinase-at the protein level using tissue microarrays consisting of over 700 clinically stratified prostate-cancer specimens. Expression of hepsin and pim-1 proteins was significantly correlated with measures of clinical outcome. Thus, the integration of cDNA microarray, high-density tissue microarray, and linked clinical and pathology data is a powerful approach to molecular profiling of human cancer.     

Changes in alanine transaminase activity in the liver of riboflavin-deficient rats

Zusammenfassung 45tägiger Riboflavinmangel bewirkte bei männlichen Albinoratten in der Leber eine Erhöhung der Alanin-Transaminase-Aktivität sowie des Pyridoxal- und Glykogengehaltes. Diese Befunde weisen darauf hin, dass die Aktivität der Nebennierenrinde beim Riboflavinmangel erhöht ist.

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Acknowledgment: The authors wish to express their sincere gratitude to Prof. S. R.Maitra, Head of the Department of Physiology, Calcutta University, for constant encouragement and for providing the laboratory facilities. The authors are also thankful to Dr.D. Sen of the Department of Applied Chemistry, Calcutta University, for translating the English summary into German.     

The identification of quantitation of extremely polar,free corticosteroids in liquor amnii

Résumé Identification et mesure quantitative des stéroÏdes libres dans le liquide amniotique. Leur concentration est supérieure à celle du cortisol et du cortisone.     

Formaldehyde-Schiff's reagent as a nucleolar stain

Summary The use of formaldehyde-Schiff's reagent as a nucleolar stain has been described. Using different digestion procedures, it was confirmed that the stain is specific for RNA. It can be suitably used as a nucleolar stain, particularly in plant materials after a short TCA extraction, which probably extracts the nonbound RNA.     

Reflexine,a new indole alkaloid ofRauwolfia reflexa

Summary Reflexine, a new indole alkaloid, has been isolated from the leaves ofRauwolfia reflexa Teijsm. and Binn. From spectral studies, chemical reactions and correlation with seredamine, reflexine is shown to be its C-17 epimer (IV).Grateful thanks are accorded to ProfessorR. H. Thomson, Dr.R. T. Brown, Dr.Nitya Nand and Dr.S. C. Pakrashi for spectral measurements. Financial assistance from CCRIMH, New Delhi, and UGC, New Delhi, are also thankfully acknowledged.     

Semaphorin 3A is a chemoattractant for cortical apical dendrites

The apical dendrites of pyramidal neurons integrate inputs from various cortical layers and are central to information processing. Here we show that the growth of apical dendrites towards the pial surface is regulated by a diffusible chemoattractant present at high levels near the marginal zone. A major component of this signal is semaphorin 3A (Sema3A), which was previously characterized as a chemorepellant for cortical axons. Soluble guanylate cyclase is asymmetrically localized to the developing apical dendrite, and is required for the chemoattractive effect of Sema3A. Thus the asymmetric localization of soluble guanylate cyclase confers distinct Sema3A responses to axons and dendrites. These observations reveal a mechanism by which a single chemotropic signal can pattern both axons and dendrites during development.