Susceptibility of beta 2-microglobulin-deficient mice to Trypanosoma cruzi infection.

The beta 2-microglobulin (beta 2m) protein associates with the products of the class I major histocompatibility (MHC) loci; this combination functions in the thymic development of and antigen presentation to CD8+ T cells. Mice in which the beta 2m gene has been disrupted by homologous recombination fail to express class I MHC gene products, and therefore lack CD8+ T cells and measurable cytotoxic T-cell responses. However, beta 2m- mice appear to have normal development of both CD4+ alpha/beta T-cell receptor (TCR+) and gamma/delta TCR+ T cells and are not overtly more susceptible than beta 2m+ mice to potential environmental agents of infection or to experimental viral infection. Here we show that beta 2m- mice suffer high parasitaemias and early death when infected with the obligate cytoplasmic protozoan parasite Trypanosoma cruzi. Despite this increased susceptibility, the beta 2m- mice are more responsive than their beta 2m+ littermates in terms of lymphokine production, making higher levels of both interleukin-2 and interferon-gamma in response to mitogen stimulation. In addition, the beta 2m- mice show essentially no inflammatory response in parasite-infected tissues. These results confirm previous experiments on mice depleted of CD8+ cells using antibody treatment in demonstrating the importance of CD8+ T cells in immune protection in T. cruzi infection. They also implicate CD8+ T cells and/or class I MHC molecules in regulation of lymphokine production and recruitment of inflammatory cells.     

Approach to a quantitative differentiation between the respiratory effects evoked from the lung stretch and the lung deflation receptors during thoracic compression

Zusammenfassung Die beiden Annahmen, dass sich bei Thoraxkompression die Verminderung der Impulssequenz der Lungendehnungsrezeptoren analog zum Lungenentdehnungsreflex auswirke, und dass sich dessen inspiratorische Atmungseffekte zu jenen des Lungenkollapsreflexes addieren, erscheinen gerechtfertigt. Diese Annahmen ermöglichen eine quantitative Differenzierung zwischen dem respiratorischen Einfluss der Lungendehnungs-und Lungenkollapsrezeptoren bei Thoraxkompression. Damit können die auf die Erregung der Lungenkollapsrezeptoren zu beziehenden Atmungsveränderungen (f,I/E) erstmals isoliert und quantitativ dargestellt werden.

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Presented at the 2nd Meeting of the Swiss Physiological Society, Zürich, 8 November 1969.     

The knockout mouse project

Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain.     

ras-Related gene sequences identified and isolated from Saccharomyces cerevisiae

The oncogenes of Harvey and Kirsten murine sarcoma viruses (v-rasH and v-rasK) and their cellular homologues (c-rasH and c-rasK) constitute two members of the ras gene family. Each functional member of the ras gene family encodes a 21,000 molecular weight protein (p21ras). ras genes have been detected in a wide variety of vertebrate species, including Xenopus laevis (R. E. Steele, personal communication), and in Drosophila melanogaster. We report here the detection of ras-related genes in the yeast Saccharomyces cerevisiae, and the isolation of two ras-related molecular clones, c-rassc-1 and c-rassc-2, from the DNA of Saccharomyces. Both c-rassc-1 and c-rassc-2 hybridize specifically to probes prepared from mammalian ras DNA. Sequencing of c-rassc-1 reveals extensive amino acid homology between the protein encoded by c-rassc-1 and the p21 encoded by c-rasH. Our studies suggest that these clones can be used to elucidate the normal cellular functions of ras-related genes in this relatively simple eukaryotic organism.     

A module map showing conditional activity of expression modules in cancer

DNA microarrays are widely used to study changes in gene expression in tumors, but such studies are typically system-specific and do not address the commonalities and variations between different types of tumor. Here we present an integrated analysis of 1,975 published microarrays spanning 22 tumor types. We describe expression profiles in different tumors in terms of the behavior of modules, sets of genes that act in concert to carry out a specific function. Using a simple unified analysis, we extract modules and characterize gene-expression profiles in tumors as a combination of activated and deactivated modules. Activation of some modules is specific to particular types of tumor; for example, a growth-inhibitory module is specifically repressed in acute lymphoblastic leukemias and may underlie the deregulated proliferation in these cancers. Other modules are shared across a diverse set of clinical conditions, suggestive of common tumor progression mechanisms. For example, the bone osteoblastic module spans a variety of tumor types and includes both secreted growth factors and their receptors. Our findings suggest that there is a single mechanism for both primary tumor proliferation and metastasis to bone. Our analysis presents multiple research directions for diagnostic, prognostic and therapeutic studies.     

Über die Wirkung von synthetischem ACTH (β 1–24Corticotropin) beim Menschen

Summary Synthetic ^1–24Corticotropin (CIBA 30920-Ba) administered intravenously over 8 h to humans produced a significant rise in free plasma 17-hydroxycorticoids, urinary 17-hydroxycorticoids and 17-ketosteroids. The logarithmic dose response curve of the urinary 17-hydroxycorticoids was linear from 3 to 25 units. The comparison of the steroidogenic effect of the synthetic and natural ACTH (Cortrophin) revealed a more rapid but less sustained activity of the synthetic product.     

Unterliegt die Heimkehrgeschwindigkeit der Brieftauben hormonalen Einflüssen?

Summary The relation between the homecoming-speed of carrier-pigeons and the influence of sexhormones and prolaktin is reported.It is further examined whether the influence of prolaktin (breeding on 10–15 days old eggs) or psychological factors (feeding of young individuals of more than 15 days) are the factors, accelerating the homecoming-speed. Best results are obtained by combining breeding 1–6 days old eggs and feeding young pigeons of 2–3 weeks.

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In memoriam Heinz Knieriem zu seinem 15. Todestage