Structural relationships between the endogenous volatile urinary metabolites of experimentally diabetic rats and certain neurotoxins

Summary High resolution glass capillary gas chromatography and GC/MS were utilized to examine qualitative and quantitative variations from normal of urinary volatile metabolites of long-term alloxan and streptozotocin diabetic rats. Volatile metabolites were structurally compared with known neurotoxins to examine any possible relationship between these metabolites and the development of the diabetic polyneuropathy.Acknowledgment. This research was supported by grant No. 24349 from the National Institute of General Medical Sciences, U.S. Public Health Service.     

A comparison of the degree of chimaerism produced when allogeneic cells from four different tissues are used to create tolerance in the mouse

Résumé La tolérance immunologique produite chez la souris avec les cellules de foie d'embryon, ou des cellules de rate, de tissus lymphoïdes ou de moelle osseuse d'adulte, a été comparée au degré de chimérisme. Le foie d'embryon a produit le plus haut degré de chimérisme (10,7%).     

The regeneration of accessory limb parts following epidermal cap transplantation in urodeles

Résumé Les événements morphogénétiques qui suivent le greffage d'un blastème apical à la face préaxiale d'un membre antérieur en voie régénératrice, chezAmbystoma, sont tout à fait normaux, mais le niveau où se localise le régénérat accessoire est différent selon l'espèce utilisé. Ces résultats sont discutés au point de vue du stimulus d'agrégation des cellules appartenant au régénérat accessoire.

---

---

This work was supported by a research grant (NB 04128) from the National Institute of Neurological Diseases and Blindness, National Institutes of Health.     

Evolution of the extracellular space in immature nervous tissue

Resumen En el cerebelo de rata recién nacida existen espacios extracelulares mayores que 1000 Å los cuales progresivamente se reducen hasta que en la tercera semana, como en el adulto, las celulas y fibras se hallan separadas por endiduras de 150–200 Å. Estas observaciones indican que el reducido espacio usualmente hallado en el adulto no es un artificio tecnico como ha sido sugerido por algunos autores.     

Use of human tissue to assess the oncogenic activity of melanoma-associated mutations

Multiple genetic alterations occur in melanoma, a lethal skin malignancy of increasing incidence. These include mutations that activate Ras and two of its effector cascades, Raf and phosphoinositide 3-kinase (PI3K). Induction of Ras and Raf can be caused by active N-Ras and B-Raf mutants as well as by gene amplification. Activation of PI3K pathway components occurs by PTEN loss and by AKT3 amplification. Melanomas also commonly show impairment of the p16(INK4A)-CDK4-Rb and ARF-HDM2-p53 tumor suppressor pathways. CDKN2A mutations can produce p16(INK4A) and ARF protein loss. Rb bypass can also occur through activating CDK4 mutations as well as by CDK4 amplification. In addition to ARF deletion, p53 pathway disruption can result from dominant negative TP53 mutations. TERT amplification also occurs in melanoma. The extent to which these mutations can induce human melanocytic neoplasia is unknown. Here we characterize pathways sufficient to generate human melanocytic neoplasia and show that genetically altered human tissue facilitates functional analysis of mutations observed in human tumors.     

TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function

Progressive kidney failure is a genetically and clinically heterogeneous group of disorders. Podocyte foot processes and the interposed glomerular slit diaphragm are essential components of the permeability barrier in the kidney. Mutations in genes encoding structural proteins of the podocyte lead to the development of proteinuria, resulting in progressive kidney failure and focal segmental glomerulosclerosis. Here, we show that the canonical transient receptor potential 6 (TRPC6) ion channel is expressed in podocytes and is a component of the glomerular slit diaphragm. We identified five families with autosomal dominant focal segmental glomerulosclerosis in which disease segregated with mutations in the gene TRPC6 on chromosome 11q. Two of the TRPC6 mutants had increased current amplitudes. These data show that TRPC6 channel activity at the slit diaphragm is essential for proper regulation of podocyte structure and function.