Genistein inhibits lysosomal enzyme release by suppressing Ca2+ influx in HL-60 granulocytes.

The tyrosine kinase inhibitor genistein (5-200 microM) suppressed Ca(2+)-dependent fMLP (1 microM) and ATP (100 microM)-induced release of the lysosomal enzyme, beta-glucuronidase from neutrophil-like HL-60 granulocytes. Agonist-induced Ca2+ mobilization resulted from the release of intracellular Ca2+ stores and the influx of extracellular Ca2+. Genistein (200 microM) suppressed fMLP (1 microM) and ATP (100 microM)-induced Ca2+ mobilization, by 30-40%. Ca2+ release from intracellular stores was unaffected by genistein, however, genistein abolished agonist-induced Ca2+ (Mn2+) influx. Consistent with these findings, genistein (200 microM) or removal of extracellular Ca2+ (EGTA 1 mM), inhibited Ca(2+)-dependent agonist-induced beta-glucuronidase release by similar extents (about 50%). In the absence of extracellular Ca2+, genistein had a small additional inhibitory effect on fMLP and ATP-induced beta-glucuronidase release, suggesting an additional inhibitory site of action. Genistein also abolished store-operated (thapsigargin-induced) Ca2+ (Mn2+) influx. Neither fMLP nor ATP increased the rate of Mn2+ influx induced by thapsigargin (0.5 microM). These data indicate that agonist-induced Ca2+ influx and store-operated Ca2+ influx occur via the same genistein-sensitive pathway. Activation of this pathway supports approximately 50% of lysosomal enzyme release induced by either fMLP or ATP from HL-60 granulocytes.

A differential assessment model for alcoholism. The scales of the Alcohol Use Inventory.

The development and use of the Alcohol Use Inventory are discussed. The scales of the Inventory allow the measurement of multiple manifestations of alcohol problems.

Production, behaviour and fertility of merino wethers, hemi-castrates with reduced testicular parenchyma and induced cryptorchids.

Greasy wool production, body weight, behaviour and fertility of male, fine wool Merino sheep were studied from 10 to 21 months of age to assess their suitability for wool production. The males were either castrated (wethers), or were hemi-castrated with a vasectomy and reduction (either partially or in full) of the parenchyma of the retained testicle, or the testicles pushed up into the inguinal canal and the scrotum shortened (induced cryptorchids). There were significant differences among all groups in body weight, with increases being associated with the larger amounts of testicular tissue present. Fertility was low in the induced cryptorchids at 19 months of age. The hemi-castrates with reduced testicular parenchyma were infertile. The hemi-castrates with reduced testicular parenchyma had significantly heavier greasy fleece weights than the wethers and induced cryptorchids, which had similar fleece weights. The wether group suffered a higher prevalence of posthitis in spring and autumn than the hemi-castrate or induced cryptorchid groups. Those hemi-castrates with the largest amount of testicular parenchyma retained and the induced cryptorchids exhibited masculine behaviour patterns and had an increased incidence of fly strike to the head. The principle of hemi-castration and reduction of the testicular parenchyma is shown to be applicable in wool producing flocks with the potential to increase greasy wool production while minimising the management and marketing limitations previously associated with induced cryptorchids.

Alcoholism and ethnicity: a comparative study of alcohol use patterns across ethnic groups.

Sociological and alcohol use patterns were studied in American Indian, Black, Hispano, and White Anglo groups of alcoholism patients. Sociological variables indicated all groups appeared to be experiencing significant disruption in social and vocational areas, with the American Indian group showing the greatest disruption across the four groups in the socioeconomic areas. The four groups did not differ as to use of alcohol to enhance self, manage anxiety and depression, or as to sustained or periodic use. American Indians and Hispanos have a greater tendency to drink gregariously, to drink more, and to have more disruption in social role functioning. The general trend was that the American Indian group revealed greater social and alcohol symptom disruption than the other three groups, thus supporting a more specialized treatment approach for American Indian alcoholism patients.

Statewide treatment outcome assessment in Colorado: the Colorado Client Assessment Record (CCAR).

Colorado has been measuring mental health treatment outcome statewide for the past four years. The data system for it is built around the Colorado Client Assessment Record ( CCAR ), a multi-dimensional checklist and Level-of-Functioning ( LOF ) measure. The CCAR is used by the Colorado Division of Mental Health for needs assessment, defining target groups, estimating bed need and doing cost-effectiveness studies. An underlying structure consisting of seven independent scales has recently been established using factor-analytic methods. A rater effect was also discovered and mathematically removed, revealing reliable and valid LOF information heretofore unknown. The improved CCAR will hasten implementation of Colorado's long-range plan for treatment outcome assessment.

Extracellular ATP triggers cyclic AMP-dependent differentiation of HL-60 cells.

Extracellular ATP and ATPgammaS (1-1000 microM) stimulated cyclic AMP (cAMP) production in undifferentiated HL-60 cells. The potency order for adenine nucleotides and adenosine was ATPgammaS > ATP >> ADP > or = AMP = Adenosine. Indomethacin (50 microM) had no effect on ATP-induced cAMP production. ATP and ATPgammaS also suppressed cell growth and induced differentiation as revealed by fMLP-stimulated beta-glucuronidase release 48 h after exposure. The potency order for the induction of fMLP-stimulated beta-glucuronidase release by adenine nucleotides and adenosine was ATPgammaS > or = ATP > ADP > AMP = Adenosine approximately 0. The protein kinase A inhibitor Rp-8-Br-cAMPS (10-200 microM) suppressed ATP-induced differentiation but had no effect on ATP-dependent growth suppression. UTP which, like ATP, activates P2U receptors on HL-60 cells, had no effect on cAMP production, cell growth, or differentiation. The data suggest the existence of a novel receptor for ATP on undifferentiated HL-60 cells that is coupled to the activation of adenylate cyclase and cAMP-dependent differentiation.

Extracellular ATP triggers cyclic AMP-dependent differentiation of HL-60 cells.

Extracellular ATP and ATP gamma S (1-1000 microM) stimulated cyclic AMP (cAMP) production in undifferentiated HL-60 cells. The potency order for adenine nucleotides and adenosine was ATP gamma S > ATP > > ADP > 3 AMP = Adenosine. Indomethacin (50 microM) had no effect on ATP-induced cAMP production. ATP and ATP gamma S also suppressed cell growth and induced differentiation as revealed by fMLP-stimulated beta-glucuronidase release 48 h after exposure. The potency order for the induction of fMLP-stimulated beta-glucuronidase release by adenine nucleotides and adenosine was ATP gamma S > 3 ATP > ADP > AMP = Adenosine approximately 0. The protein kinase A inhibitor Rp-8-Br-cAMPS (10-200 mM) suppressed ATP-induced differentiation but had no effect on ATP-dependent growth suppression. UTP which, like ATP, activates P2U receptors on HL-60 cells, had no effect on cAMP production, cell growth, or differentiation. The data suggest the existence of a novel receptor for ATP on undifferentiated HL-60 cells that is coupled to the activation of adenylate cyclase and cAMP-dependent differentiation.