Effect of diabetes on the vertebral column of rats and its modification by estradiol

Summary In vertebrae of genetically selected sucrose-fed diabetic rats a statistically significant bone deficit was found after diabetes had been present for about 8 months. No osteopenia was observed in diabetic rats following treatment with estrogenic hormone for 5–7 months. The development of osseous centers in the end plates of the vertebrae was retarded in diabetic rats, but was about normal in diabetic rats given estrogen.—No differences were noted in the growth zones or in the tendency to develop articular lesions in rats of the various groups. Possible differences in the amount of GAG in intervertebral discs of diabetic and non-diabetic rats respectively await further confirmation.These investigations were aided by grant No. 2 RO1 EYO 1837-03, of the Institute of Arthritis and Metabolic Disease, National Institutes of Health, Bethesda, Maryland, USA.We are indebted to Professor Dr J. Rüttner, Institute of Pathology, University of Zürich, for his permission to use the calculator.     

PITC derivatives in amino acid analysis

Refined methods for separating PTC-amino acids on reverse phase columns may pose a challenge to traditional ion exchange techniques.     

Immunochemical analysis of the surface of the sea urchin egg -an approach to the study of fertilization

Zusammenfassung Im vorliegenden Aufsatz wird über die Ergebnisse immunologischer und immunochemischer Untersuchungen der Oberfl?chenstrukturen der Eier einiger mediterraner Seeigelarten berichtet. Die Eier werden Antiserum ausgesetzt, das durch Einspritzungen von Seeigel-Gametenmaterial in Kaninchen gewonnen wurde. So erh?lt man eine Reihe mikroskopisch sichtbarer, artspezifischer Antwortreaktionen. Normales Kaninchenserum ist unwirksam. Durch das vergleichende Studium der Aktivit?t verschiedener Antiseren, sowie durch die Antiserum-Hemmtechnik wurden bis jetzt vier voneinander verschiedene Oberfl?chenantigene bei den Eiern vonParacentrotus lividus festgestellt. Mindestens zwei der gefundenen Antigene haben Polysaccharid-Charakter. Die Reaktionen zwischen einem bestimmten Antik?rper und dessen Antigen, das A-Antigen genannt wurde, k?nnen interessanterweise zur parthenogenetischen Aktivierung unbefruchteter Eier führen. Andere Antigen-Antik?rperreaktionen k?nnen Befruchtung und Entwicklung der Eier hemmen. Die m?gliche Bedeutung der verschiedenen Antigene für das Festsetzen der Spermien an der Oberfl?che der Eier sowie für den Beginn der Ei-Aktivierung wird besprochen.      

Meiotic arrest and aneuploidy in MLH3-deficient mice

MutL homolog 3 (Mlh3) is a member of a family of proteins conserved during evolution and having dual roles in DNA mismatch repair and meiosis. The pathway in eukaryotes consists of the DNA-binding components, which are the homologs of the bacterial MutS protein (MSH 2 6), and the MutL homologs, which bind to the MutS homologs and are essential for the repair process. Three of the six homologs of MutS that function in these processes, Msh2, Msh3 and Msh6, are involved in the mismatch repair of mutations, frameshifts and replication errors, and two others, Msh4 and Msh5, have specific roles in meiosis. Of the four MutL homologs, Mlh1, Mlh3, Pms1 and Pms2, three are involved in mismatch repair and at least two, Pms2 and Mlh1, are essential for meiotic progression in both yeast and mice. To assess the role of Mlh3 in mammalian meiosis, we have generated and characterized Mlh3(-/-) mice. Here we show that Mlh3(-/-) mice are viable but sterile. Mlh3 is required for Mlh1 binding to meiotic chromosomes and localizes to meiotic chromosomes from the mid pachynema stage of prophase I. Mlh3(-/-) spermatocytes reach metaphase before succumbing to apoptosis, but oocytes fail to complete meiosis I after fertilization. Our results show that Mlh3 has an essential and distinct role in mammalian meiosis.     

Gene expression profiling predicts clinical outcome of breast cancer

Breast cancer patients with the same stage of disease can have markedly different treatment responses and overall outcome. The strongest predictors for metastases (for example, lymph node status and histological grade) fail to classify accurately breast tumours according to their clinical behaviour. Chemotherapy or hormonal therapy reduces the risk of distant metastases by approximately one-third; however, 70-80% of patients receiving this treatment would have survived without it. None of the signatures of breast cancer gene expression reported to date allow for patient-tailored therapy strategies. Here we used DNA microarray analysis on primary breast tumours of 117 young patients, and applied supervised classification to identify a gene expression signature strongly predictive of a short interval to distant metastases ('poor prognosis' signature) in patients without tumour cells in local lymph nodes at diagnosis (lymph node negative). In addition, we established a signature that identifies tumours of BRCA1 carriers. The poor prognosis signature consists of genes regulating cell cycle, invasion, metastasis and angiogenesis. This gene expression profile will outperform all currently used clinical parameters in predicting disease outcome. Our findings provide a strategy to select patients who would benefit from adjuvant therapy.