Plasmatic levels of glucose and insulin in siblings of diabetic children (author's transl)

Observation of glucose and plasmatic insulin curve after oral administration of glucose in 16 brothers of juvenile diabetics. The findings were: slight curve alterations that would be compatible with chemical diabetes.     

Marijuana and hyperthermia

The present paper reports the variability of PTC taste sensitivity among eight endogamous tribal populations inhabiting the Eastern Ghats of North Coastal Andhra Pradesh. It was compared with the genetic diversity of PTC taste sensitivity among tribal and caste populations of Andhra Pradesh. The tribal and caste groups present a relatively high genetic diversity, of which a major proportion is due to genetic differences within populations rather than that between populations. Castes show a higher heterogeneity than tribes, the difference being significant. The high genetic diversity found among Andhra populations may be attributed to social stratification and the practice of strict endogamy.     

(+)-4-[2-[4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5, 6]cyclohepta[1,2-b]- pyridin-11(R)-yl)-1-piperidinyl]-2-oxo-ethyl]-1-piperidinecarboxamid e (SCH-66336): a very potent farnesyl protein transferase inhibitor as a novel antitumor agent

We have previously shown that appropriate modification of the benzocycloheptapyridine tricyclic ring system can provide potent farnesyl protein transferase (FPT) inhibitors with good cellular activity. Our laboratories have also established that incorporation of either pyridinylacetyl N-oxide or 4-N-carboxamidopiperidinylacetyl moieties results in pharmacokinetically stable inhibitors that are orally efficacious in nude mice. We now demonstrate that further elaboration of the tricyclic ring system by introducing a bromine atom at the 7- or the 10-position of the 3-bromo-8-chlorotricyclic ring system provides compounds that have superior potency and selectivity in FPT inhibition. These compounds have good serum levels and half-lives when given orally to rodents and primates. In vitro and in vivo evaluation of a panel of these inhibitors has led to identification of 15 (SCH 66336) as a highly potent (IC50 = 1.9 nM) antitumor agent that is currently undergoing human clinical trials.     

Production of monoclonal antibodies specific for the i and 1,2 flagellar antigens of Salmonella typhimurium and characterization of their respective epitopes

Salmonella typhimurium expresses two antigenically distinct flagellins, each containing a different H antigen (i and 1,2), the combination of which is highly specific for this serotype. In this study, overlapping recombinant flagellin fragments were constructed from the fliC (H:i) and fljB (H:1,2) flagellin genes, and the expression products were tested for binding to H antigen-specific monoclonal and polyclonal antibodies. A minimal area, 86 amino acids for H:i and 102 amino acids for H:1,2, located in the central variable domain of each flagellin was required for the binding of serotype-specific antibodies, providing further evidence for the presence of a discontinuous H epitope. Two peptides comprising these areas were shown to be highly suitable for application as antigens in an enzyme-linked immunosorbent assay detecting S. typhimurium-specific antibody.     

Pattern of expression of highly polysialylated neural cell adhesion molecule in the developing and adult rat striatum

In rats, morphological and synaptic maturation of the striatum, a brain area involved in the control of movement and in cognitive behaviour, proceeds for several weeks postnatally. Little is known, however, about the molecular events associated with the final maturation of the striatum. In particular, there is little information on molecules playing a role in cell adhesion, a phenomenon of particular importance for neuronal development. We have examined the time course and topography of expression of the highly polysialylated form of the neural cell adhesion molecule in the rat striatum during postnatal development and in the adult, and compared it to growth-associated protein-43, a marker of axonal growth. As earlier during development [Aaron L. I. and Chesselet M.-F. (1989) Neuroscience 28, 701-710], immunolabelling for polysialylated neural cell adhesion molecule was very intense in the entire striatum at postnatal days 17-19. At postnatal days 21 and 22, loss of polysialylated neural cell adhesion molecule immunoreactivity in the caudal part of the striatum contrasted with the persistence of immunoreactivity at more rostral levels. Most of the striatum was devoid of polysialylated neural cell adhesion molecule immunoreactivity by postnatal day 25. At this age, as well as in the striatum of adult rats, immunolabelling was only observed along the ventricular edge of the striatum. In contrast to polysialylated neural cell adhesion molecule immunoreactivity, immunolabelling for growth-associated protein-43 had reached its adult pattern by postnatal day 17, indicating that polysialylated neural cell adhesion molecule persists beyond the period of major axonal growth. In the adult, an area of stronger growth associated protein-43 immunoreactivity overlapped with the region which retained immunoreactivity to polysialylated neural cell adhesion molecule. The results indicate that, in the developing rat striatum, the neural cell adhesion molecule remains highly sialylated not only during the ingrowth of cortical and nigral inputs but also during the formation of dendritic spine and synaptogenesis. Loss of polysialyated neural cell adhesion molecule occurs at the time of emerging spontaneous activity in cerebral cortex, and precedes the development of mature responses to cortical stimulation and adult membrane properties in a majority of striatal neurons.     

Role of calcium oxalate monohydrate crystal interactions with renal epithelial cells in the pathogenesis of nephrolithiasis: a review

Renal tubular fluid in the distal nephron is supersaturated with calcium and oxalate ions that nucleate to form crystals of calcium oxalate monohydrate (COM), the most common crystal in renal stones. How these nascent crystals are retained in the nephron to form calculi in certain individuals is not known. Recent studies from this laboratory have demonstrated that COM crystals can bind within seconds to the apical surface of renal epithelial cells, suggesting one mechanism whereby crystals could be retained in the tubule. Adherence of crystals to cells along the nephron may be opposed by specific urinary anions such as glycosaminoglycans, uropontin, nephrocalcin, and citrate. In culture, adherent crystals are quickly internalized by renal cells, and reorganization of the cytoskeleton, alterations in gene expression, and initiation of proliferation can ensue. Each of these cellular events appears to be regulated by extracellular factors. Identification of molecules in tubular fluid and on the cell surface that determine whether a crystal-cell interaction results in retention of the crystal or its passage out of the nephron appears critical for understanding the pathogenesis of nephrolithiasis.