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G D Schellenberg

Publications and source records attributed to G D Schellenberg.

113 records · Page 7Linked to original sources

Sodium-dependent and calcium-dependent calcium transport by rat brain microsomes.

Microsomal vesicles prepared from rat brain contain a Na+-Ca2+ exchange transport system capable of accumulating Ca2+ in a time- and temperature-dependent manner. The Ca2+ accumulated by these vesicles was released by the Ca2+ ionophore A23187 but not by EGTA. The Km value for Ca2+ uptake was 23 microM with a maximal velocity of 21 nmol Ca2+/mg per min. Ca2+ uptake was significantly inhibited by La3+, Sr2+, Mn2+ and Ba2+ and to a lesser extent by Mg2+. 45Ca2+ accumulated by Na+-dependent uptake could be released by 40Ca2+, indicating the presence of a Ca2+-Ca2+ exchange activity in the microsomes. Ca2+-Ca2+ exchange was stimulated in Li+- and K+-containing media as compared to choline+ media. Microsomes also catalyzed ATP-dependent Ca2+ uptake (in the absence of Na+ gradient). The Ca2+ sequestered by this mechanism could be released by extravesicular Na+, indicating that both the ATP-dependent and the Na+-dependent Ca2+ uptake systems are present in the same membrane. The microsomal preparation used did not contain measurable amounts of succinate dehydrogenase activity or oligomycin-azide-dinitrophenol sensitive ATP-dependent Ca2+ uptake. Thus, the Ca2+ accumulation observed was not due to contaminating mitochondria. The preparation was enriched for 5'-nucleotidase and (Na+ + K+)-ATPase (plasma membrane markers) as well as antimycin A-resistant NADPH-dependent cytochrome c reductase activity (an endoplasmic reticulum marker).

Adenosine Triphosphate↗

Evidence for etiologic heterogeneity in Alzheimer's disease.

We briefly describe the evidence for etiologic heterogeneity in Alzheimer's disease. Several different genetic and environmental factors may act separately or in combination to produce the AD phenotype. This potential heterogeneity presents special challenges to those attempting to identify specific genetic influences in the pathogenesis of AD.

Alzheimer Disease↗

Relationship between serum alpha 1-antichymotrypsin and Alzheimer's disease.

We obtained serum samples and measured alpha 1-antichymotrypsin (ACT) levels in 36 pairs of consecutive probable Alzheimer's disease (AD) patients and age- and sex-matched, cognitively intact control subjects. Serum ACT was measured by radial immunodiffusion. Unique to this study, we found that ACT levels rose significantly with age within controls (but not within AD cases), thus ACT may be related to the aging process. Consistent with other reports, we found that AD cases had greater serum ACT in 27 of 36 pairs [mean difference = 135.5 (SE = 50.8) mg/l (p < 0.05)]. Severity and duration of AD were not significantly associated with the observed difference. The ACT increase observed in AD is not sufficient to recommend ACT's use as a diagnostic marker for AD. Because adult Down's syndrome (DS) persons are known to have pathologic features of AD, we also measured serum ACT levels in 11 adult, noninstitutionalized, DS persons paired with 11 age- and sex-matched, volunteer control subjects; we found no statistically significant difference. The unexpected age-associated increase in ACT among normal controls could be an indicator of early amyloid plaque formation. Future studies comparing ACT levels in both serum and cerebrospinal fluid should help to clarify the origin of ACT found in amyloid plaques and its value as a diagnostic marker for AD.

Adult↗

Evidence for an interaction between apolipoprotein E genotype, gender, and Alzheimer disease.

Carriers of the apolipoprotein E (APOE) epsilon4 allele show significantly higher risk of Alzheimer disease (AD). The aim of this present study was to test the hypothesis that a significant interaction exists between APOE genotype and gender on AD. Interactions of epsilon4 by gender, although indicated in the literature, require further verification. A total of 195 past or current control or AD participants in an ongoing longitudinal study of aging and dementia were genotyped. All subjects were at least 60 years old; demented subjects met clinical or pathologic criteria for late-onset AD. Logistic regression analysis and proportional hazard models were used to evaluate joint effects of APOE and gender. A significant statistical interaction between APOE and gender was shown (p = 0.04) in logistic regression analysis. Women carrying one or more APOE-epsilon4 allele were more likely to develop AD [odds ratio (OR) = 7.8, 95% confidence interval (CI) = 3.2-19. 1]. For men, the presence of the APOE-epsilon4 allele was not associated with a statistically significant increased risk (OR = 1.6, 95% CI = 0.5-5.3). The interaction term in the proportional hazards model neared (p = 0.07) statistical significance, and a similar but reduced gender effect was shown. The analysis suggests that the presence of one or more APOE-epsilon4 allele confers a substantially greater risk of AD to women than to men. These findings in part may account for reports of increased risk of AD faced by women.

Aged↗