Further studies on hepatic acidic glycosaminoglycans in the Hurler syndrome.

Acid GAG were isolated from hepatic tissue from 3 patients with Hurler syndrome and 3 normal controls. Gross elevations in the uronic acid and hexosamine contents were found in Hurler livers compared with the normal ones. The total GAG concentration was significantly increased (about 25fold) in Hurler patients.     

The exudative diathesis produced by torula yeast

Zusammenfassung Die exsudative Diathese, welche bei Küken durch Verfütterung einer Vitamin-E-freien Nahrung mit Torulahefe als Proteinquelle hervorgerufen wird, wird mit dem nicht unbeträchtlichen Gehalt dieser Hefe an leicht oxydierbaren Fettsäuren in Verbindung gesetzt.Die Vitamin-E-freie Torula-Hefe-Nahrung führt zu Peroxydation des Körperfettes, wie es früher in entsprechenden Versuchen mit Kasein-Lebertran-Nahrungen gefunden wurde.Die von amerikanischen Forschern gefundene Schutzwirkung von Selen gegen exsudative Diathese wird bestätigt.Das Auftreten von Encephalomalacie wurde durch Selen nicht verhindert.

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We are grateful to Lake States Yeast Corporation, Rhinelander, Wisconsin, for supply of the torula yeast used in these experiments.     

The acidic glycosaminoglycans in gastric mucosa of athyroid rats: The effects of L-tri-iodothyronine

Summary Hyaluronic acid is increased about 12%, whereas dermatan sulfate is decreased about 34%, in gastric mucosa of athyroid rats when compared with controls. Administration of 2 doses of L-tri-iodothyronine reversed the effects of thyroidectomy.This work was partially supported by the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina.     

Further studies on gel filtration of urinary substances.

Urine specimens from healthy children were concentrated and filtered through Sephadex G-100 and G-25. The eluate was recovered in fractions of 5 ml each. Total hexoses, galactose, total proteins and total uronic acids were determined on each fraction. Total hexoses and galactose were eluted in 6 distinct peaks. The uronic acid containing GAG were eluted in 4 small peaks on G-25 and 1 peak on G-100. This peak is eluted always with high amounts of galactose containing glycoproteins.     

Effect of hydrocortisone administration on erythropoiesis in the adrenalectomized dog

Resumen La administración de 2 mg/kg/día de hidrocortisona durante 40 días en perros adrenalectomizados 4 meses antes produjo elevación del volumen de la masa roja circulante y de la síntesis de hemoglobina. El tratamiento con la hormona en la dosis de 4 mg/kg/día durante los siguientes 40 días produjo más aumento de la actividad eritropoyética de la médula ósea, una gran proporción de la cuál fue inefectiva en términos de producción de eritrocitos, produciéndose un descenso de la masa roja circulante.

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Member of the Carrera del Investigador Científico del Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina.

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This work was supported by Grant No. 1126d from the Consejo Nacional de Investigaciones Cientificas y Técnicas de la República Argentina.     

Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity

Inflammasomes are a family of cytosolic multiprotein complexes that initiate innate immune responses to pathogenic microbes by activating the caspase 1 protease. Although genetic data support a critical role for inflammasomes in immune defence and inflammatory diseases, the molecular basis by which individual inflammasomes respond to specific stimuli remains poorly understood. The inflammasome that contains the NLRC4 (NLR family, CARD domain containing 4) protein was previously shown to be activated in response to two distinct bacterial proteins, flagellin and PrgJ, a conserved component of pathogen-associated type III secretion systems. However, direct binding between NLRC4 and flagellin or PrgJ has never been demonstrated. A homologue of NLRC4, NAIP5 (NLR family, apoptosis inhibitory protein 5), has been implicated in activation of NLRC4 (refs 7-11), but is widely assumed to have only an auxiliary role, as NAIP5 is often dispensable for NLRC4 activation. However, Naip5 is a member of a small multigene family, raising the possibility of redundancy and functional specialization among Naip genes. Here we show in mice that different NAIP paralogues determine the specificity of the NLRC4 inflammasome for distinct bacterial ligands. In particular, we found that activation of endogenous NLRC4 by bacterial PrgJ requires NAIP2, a previously uncharacterized member of the NAIP gene family, whereas NAIP5 and NAIP6 activate NLRC4 specifically in response to bacterial flagellin. We dissected the biochemical mechanism underlying the requirement for NAIP proteins by use of a reconstituted NLRC4 inflammasome system. We found that NAIP proteins control ligand-dependent oligomerization of NLRC4 and that the NAIP2-NLRC4 complex physically associates with PrgJ but not flagellin, whereas NAIP5-NLRC4 associates with flagellin but not PrgJ. Our results identify NAIPs as immune sensor proteins and provide biochemical evidence for a simple receptor-ligand model for activation of the NAIP-NLRC4 inflammasomes.