Detection of specific and 'constitutive' antibody secreting cells in the gills, head kidney and peripheral blood leucocytes of dab (Limanda limanda)

The relative immunological importance of the gills of fish was investigated in terms of antibody production by enumerating antibody secreting cells (ASC) in the gills, head kidney and blood of dab (Limanda limanda) using the ELISPOT assay. The contribution of 'constitutive' ASC in the gill appeared more substantial than that of elicited specific ASC. The gills were found to contain a mean (+/- SD) of 4227 +/- 1029 'constitutive' ASC/10(6) cells which was fewer than the head kidney which contained a mean (+/- SD) of 15617 +/- 3723 'constitutive' ASC/10(6) cells but more than peripheral blood leucocytes which contained a mean (+/- SD) of 2650 +/- 212 'constitutive' ASC/10(6) cells. The number of specific anti-human gamma globulin (HGG) ASC following parenteral or oral administration of HGG was also determined. Anti-HGG ASC were detected in all three tissues following parenteral immunization, peaking simultaneously, 4 weeks post-immunization. The strongest response was found in the head kidney. After oral immunization, responses were much weaker: again the head kidney was the most active but the gill response was barely detectable. These data were complemented by measurement of specific antibody in the serum by ELISA. Serum antibody titres following immunization were found to correlate closely with the number of specific ASC in the head kidney following parenteral immunization whereas serum antibody titres after oral administration of antigen most closely followed the number of specific ASC in the blood. In the light of these data it is suggested that the primary immunological role of the leucocytes in the gill may be in the earliest stages of defence against infection.     

Patterns of visual field progression in patients with retinitis pigmentosa

OBJECTIVE: The purpose of the study was to determine whether distinct patterns of visual field progression are present in patients with retinitis pigmentosa (RP) and to evaluate the correlation between these patterns, if present, and different genetic subtypes of RP. DESIGN: A retrospective analysis of patterns of visual field progression in RP was performed. PARTICIPANTS: Visual fields of 162 patients with RP, including 55 with type 2 Usher syndrome, who had at least 3 Goldmann visual field examinations during a period of at least 3 years were reviewed. MAIN OUTCOME MEASURES: Goldmann visual fields. RESULTS: Visual fields of 86 patients could be classified into one of three specific patterns of visual field progression. Pattern I included those patients with a progressive concentric loss of visual fields; pattern II included those with visual field loss that began superiorly and subsequently developed an arcuate scotoma that progressed either from the nasal (IIA) or the temporal (IIB and IIC) side; and pattern III included patients whose visual field loss was characterized initially by a complete or incomplete midperipheral "ring scotoma" that broke through into the periphery. The end stage of all these patterns was a residual central visual field, sometimes also associated with a small peripheral island. In 53 of the 162 patients, the pattern of visual field loss could not be categorized because of an advanced stage of field loss at the time of the initial examination. CONCLUSIONS: Distinctive patterns of visual field progression can be observed in patients with retinitis pigmentosa and type 2 Usher syndrome. There were no intrafamilial variations in the pattern of visual field loss in our data on 24 patients from 11 families. Within certain genetic subtypes, there was a predilection for a preponderance of a specific pattern of visual field progression. Future studies may be able to correlate these patterns of visual field loss with different genetic mutations. A greater understanding as to why certain patterns of field loss exist could potentially provide greater insight into the various pathogenetic mechanism(s) by which photoreceptor cells degenerate in this group of patients.     

Patients' experiences of Parkinson's disease

Patients' (n = 101) experiences of Parkinson's disease (PD) were studied through structured interviews. Oblique factor analysis produced three moderately intercorrelated clusters of items reflecting reported severity of motoric, cognitive, and psychological problems, respectively. Scales formed from the factors were correlated with demographic, disease-related, and psychosocial variables. The demographic variables were not significantly correlated with the scales or with any other variables in the set. Hoehn and Yahr staging was significantly related to scores only on the motoric severity scale. Measures of functional capacity, in contrast, were significantly associated with all three scales. Although the addition of the psychosocial variables as a set significantly increased multiple Rs for each of the three scales, the specific patterns of correlation varied from scale to scale. The findings indicate that from the viewpoint of the patient the problems created by PD were not restricted to the motoric domain. Too narrow a focus by clinicians and researchers on medical symptomatology may give insufficient recognition to the multidimensional nature of the patient's experience.     

Macro-to-micro links in the relation between income inequality and mortality

A growing literature points to links between income inequality and mortality. Any examination of the link should distinguish, both theoretically and empirically, between shifts in inequality that result from changes in the bottom and top of the income distribution. When state-level data from the U.S. censuses of 1980 and 1990 were used to measure differences in mortality, the results indicated that inequality measures reflecting depth of poverty show stronger correlations with mortality than do inequality measures reflecting heights of affluence. In addition, longitudinal data from the Panel Study of Income Dynamics were used to related state-level inequality measures to individual-level data on mortality. This comparison revealed significant associations between degree of income inequality in state of residence and individual risk of death only for nonelderly individuals with middle-class incomes in 1990.     

Effects of the angiotensin II type-1 receptor antagonist ZD7155 on angiotensin II-mediated regulation of renin secretion and renal renin gene expression, renal vasoconstriction, and blood pressure in rats

Angiotensin II receptors have recently been subclassified as type-1 or type-2 receptors. The in vitro and in vivo effects of blocking the angiotensin II type-1 receptor with ZD7155, an angiotensin II type-1 selective receptor antagonist, have been studied in angiotensin II-mediated increases in cytosolic calcium in rat mesangial cells, in angiotensin II-induced renal and systemic vasoconstriction, and in angiotensin II-mediated regulation of renin secretion and renal renin gene expression. ZD7155 completely blocked the ability of angiotensin II to elicit an increase in free intracellular calcium concentrations in rat mesangial cells. In isolated perfused rat kidneys, ZD7155 completely abolished the angiotensin II-induced vasoconstriction and increased renin secretion to 700% of baseline levels. Furthermore, ZD7155 decreased systolic blood pressure by 16 mm Hg, increased plasma renin activity 3.7-fold, and stimulated renal renin gene expression 4.2-fold in Sprague-Dawley rats in vivo. Our results suggest that ZD7155 is a potent antagonist of the angiotensin II type-1 receptor, which mediates angiotensin II-induced increases of free intracellular calcium concentrations in (e.g., renal mesangial cells), constriction of the renal and systemic vasculature, and inhibition of renin secretion and synthesis.     

Cumulative impact of sustained economic hardship on physical, cognitive, psychological, and social functioning

BACKGROUND: Although the relation between low income and poor health is well established, most previous research has measured income at only one time. METHODS: We used income information collected in 1965, 1974, and 1983 from a representative sample of adults in Alameda County, California, to examine the cumulative effect of economic hardship (defined as a total household income of less than 200 percent of the federal poverty level) on participants who were alive in 1994. RESULTS: Because of missing information, analyses were based on between 1081 and 1124 participants (median age, 65 years in 1994). After adjustment for age and sex, there were significant graded associations between the number of times income was less than 200 percent of the poverty level (range, 0 to 3) and all measures of functioning examined except social isolation. As compared with subjects without economic hardship, those with economic hardship in 1965, 1974, and 1983 were much more likely to have difficulties with independent activities of daily living (such as cooking, shopping, and managing money) (odds ratio, 3.38; 95 percent confidence interval, 1.49 to 7.64), activities of daily living (such as walking, eating, dressing, and using the toilet) (odds ratio, 3.79; 95 percent confidence interval, 1.32 to 9.81), and clinical depression (odds ratio, 3.24; 95 percent confidence interval, 1.32 to 7.89) in 1994. We found little evidence of reverse causation -- that is, that episodes of illness might have caused subsequent economic hardship. CONCLUSIONS: Sustained economic hardship leads to poorer physical, psychological, and cognitive functioning.     

Sodium nitrite alone protects the brain microsomal Ca(2+)-ATPase against potassium cyanide-induced neurotoxicity in rats

The effect of a short-term oral administration of potassium cyanide (KCN) (200 ppm in diet) with or without sodium nitrite (NaNO2) pretreatment on rat brain microsomal Ca2 +/- ATPase was investigated. The specific activity value of the enzyme significantly decreased (p < 0.05) by 50% compared with control and by 63% for KCN-treated rats compared with KCN-treated rats pretreated with NaNO2. There was no significant difference at the h = 0.05 level between the values obtained for the control and KCN-treated rats pretreated with NaNO2. These results show both that feeding lowers brain microsomal Ca(2+)-ATPase activity and that NaNO2 has a protective role (antidote function) in that respect.     

Activation of signal transduction kinases by tamoxifen

PURPOSE: To study the signal transduction mechanisms of tamoxifen via the activation of MAPKs, JNK and ERK in order to understand its regulation of gene expression. METHODS: The effects of tamoxifen (TAM) on the activation of serine/threonine mitogen-activated protein kinase (MAPK, p42/ERK2) and the stress-activated protein kinases (p46 SAPK or c-Jun N-terminal kinase, JNK1) were evaluated using a human cervical epitheloid carcinoma HeLa cell line. RESULTS: TAM activated both JNK1 and ERK2 activities in a time- and dose-dependent manner in HeLa cells. The activation of JNK1 was enhanced when the cells were pretreated with prooxidant H2O2. CONCLUSIONS: These studies show that TAM activates the signal transduction kinases, JNK1 and ERK2, which may play important roles in the regulation of gene expression by TAM.