HIV-specific cytotoxic T lymphocytes in seropositive individuals

Virus-specific cytotoxic T lymphocytes (CTL) which kill virus-infected cells are thought to be a major host defence against viral infections. Here we report the existence of human immunodeficiency virus (HIV)-specific CTL in persons infected with this virus, the aetiological agent of AIDS (acquired immunodeficiency syndrome). Recombinant HIV-vaccinia viruses were used to express HIV antigens in B-cell lines established from subjects seropositive for HIV and seronegative controls. Circulating lymphocytes capable of killing HIV env-expressing autologous B cells were detected in eight of eight seropositive subjects; in addition, at least three seropositive subjects demonstrated gag-specific cytotoxic responses. No HIV-specific cytotoxicity was observed in seronegative subjects. Selective inhibition of the env-specific cytotoxicity by a CD3-specific monoclonal antibody indicates that the effectors are T cells. This demonstration of a cytotoxic T-cell immune response to HIV in infected individuals should prove useful in investigating the immunopathogenesis of HIV infection further and in evaluating AIDS vaccine strategies.     

Oscillation and noise determine signal transduction in shark multimodal sensory cells

Oscillating membrane potentials that generate rhythmic impulse patterns are considered to be of particular significance for neuronal information processing. In contrast, noise is usually seen as a disturbance which limits the accuracy of information transfer. We show here, however, that noise in combination with intrinsic oscillations can provide neurons with particular encoding properties, a discovery we made when recording from single electro-sensory afferents of a fish. The temporal sequence of the impulse trains indicates oscillations that operate near the spike-triggering threshold. The oscillation frequency determines the basic rhythm of impulse generation, but whether or not an impulse is actually triggered essentially depends on superimposed noise. The probability of impulse generation can be altered considerably by minor modifications of oscillation baseline and amplitude, which may underlie the exquisite sensitivity of these receptors to thermal and electrical stimuli. Additionally, thermal, but not electrical, stimuli alter the oscillation frequency, allowing dual sensory messages to be conveyed in a single spike train. These findings demonstrate novel properties of sensory transduction which may be relevant for neuronal signalling in general.     

Germline KRAS mutations cause Noonan syndrome

Noonan syndrome (MIM 163950) is characterized by short stature, facial dysmorphism and cardiac defects. Heterozygous mutations in PTPN11, which encodes SHP-2, cause approximately 50% of cases of Noonan syndrome. The SHP-2 phosphatase relays signals from activated receptor complexes to downstream effectors, including Ras. We discovered de novo germline KRAS mutations that introduce V14I, T58I or D153V amino acid substitutions in five individuals with Noonan syndrome and a P34R alteration in a individual with cardio-facio-cutaneous syndrome (MIM 115150), which has overlapping features with Noonan syndrome. Recombinant V14I and T58I K-Ras proteins show defective intrinsic GTP hydrolysis and impaired responsiveness to GTPase activating proteins, render primary hematopoietic progenitors hypersensitive to growth factors and deregulate signal transduction in a cell lineage-specific manner. These studies establish germline KRAS mutations as a cause of human disease and infer that the constellation of developmental abnormalities seen in Noonan syndrome spectrum is, in large part, due to hyperactive Ras.     

Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis

Multiple sclerosis is a demyelinating neurodegenerative disease with a strong genetic component. Previous genetic risk studies have failed to identify consistently linked regions or genes outside of the major histocompatibility complex on chromosome 6p. We describe allelic association of a polymorphism in the gene encoding the interleukin 7 receptor alpha chain (IL7R) as a significant risk factor for multiple sclerosis in four independent family-based or case-control data sets (overall P = 2.9 x 10(-7)). Further, the likely causal SNP, rs6897932, located within the alternatively spliced exon 6 of IL7R, has a functional effect on gene expression. The SNP influences the amount of soluble and membrane-bound isoforms of the protein by putatively disrupting an exonic splicing silencer.     

Disputanda Differenzierung der Wirkung von Desinfizienzienin vitro,von W. Schuler

Ohne Zusammenfassung     

Activities of cystathionase,cysteine sulphinic acid decarboxylase and serine dehydrase in the liver of tumour-bearing rats

Résumé Dans le foie de rats porteurs de tumeurs (épithéliome de Guérin et sarcome de l'estomac), les activités de la cystathionase, de la décarboxylase de l'acide cysteine sulfinique et de la sérine déhydrase sont considérablement diminuées: cette diminution est de l'ordre de 50%, 15 jours après implantation de ces tumeurs. Si à ce moment le sarcome (qui ne provoque pas de métastases) est chirurgicalement extirpé, on observe une restauration des activités enzymatiques qui, après 15 jours, est totale pour la cystathionase et très significative pour la décarboxylase.

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Equipe de Recherche C.N.R.S. No. 43.     

Tumor isoimmunity

Zusammenfassung Einige neue Ergebnisse auf dem Gebiete der Tumor-Immunität werden mit der Literatur in Einklang gebracht, und eine Hypothese zur spontanen Tumorbildung wird vorgeschlagen. Ferner wird auf die Notwendigkeit eingegangen, bei Tumor-Isoimmunitäts-Experimenten Spontantumoren zu verwenden an Stelle von lange transplantierten, vonin vitro entstandenen oder durch Karzinogene erzeugten Tumoren.

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Assisted by grants from the National Cancer Institute of the National Institutes of Health, Public Health Service; the American Cancer Society upon recommendation of the Committee on Growth of the National Research Council; and the Minnesota Division of the American Cancer Society.     

Sur les caractéristiques histologiques des petits vaisseaux pulmonaires

Zusammenfassung Histologische Untersuchungen, die unter lebensnahen Bedingungen am Kaninchen durchgeführt wurden, zeigen, dass die Wand der kleinsten Lungenvenen aus elastischem Gewebe besteht. In der Wand der kleinen Lungenarterien bestehen unter normalen Verhältnissen Verdoppelungen und Vervielfachung der elastischen Lamellen, die an die als proliferative Elastose in der menschlichen Pathologie beschriebenen Veränderungen erinnern. Bilder von in Funktion befindlichen arteriovenösen Anastomosen deuten darauf hin, dass die sogenannten Sperrarterien der Lunge keine mit «Sondervorrichtungen» versehenen Gefässe sind, sondern dass es sich um Arterien handelt, deren Muskulatur im Kontraktionszustand fixiert ist.