Inhaled corticosteroids and bone density.
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Adrenal Cortex Hormones↗
Biomedical subjects
E Patel
Publications and source records attributed to E Patel.
p38 kinase is activated in the Alzheimer's disease brain.
The p38 mitogen-activated protein kinase is a stress-activated enzyme responsible for transducing inflammatory signals and initiating apoptosis. In the Alzheimer's disease (AD) brain, increased levels of phosphorylated (active) p38 were detected relative to age-matched normal brain. Intense phospho-p38 immunoreactivity was associated with neuritic plaques, neuropil threads, and neurofibrillary tangle-bearing neurons. The antibody against phosphorylated p38 recognized many of the same structures as an antibody against aberrantly phosphorylated, paired helical filament (PHF) tau, although PHF-positive tau did not cross-react with the phospho-p38 antibody. These findings suggest a neuroinflammatory mechanism in the AD brain, in which aberrant protein phosphorylation affects signal transduction elements, including the p38 kinase cascade, as well as cytoskeletal components.
Aged↗
N-terminal heterogeneity of parenchymal and cerebrovascular Abeta deposits.
The goals of this study were twofold: to determine whether species differences in Abeta N-terminal heterogeneity explain the absence of neuritic plaques in the aged dog and aged bear in contrast to the human; and to compare Abeta N-terminal isoforms in parenchymal vs cerebrovascular Abeta (CVA) deposits in each of the species, and in individuals with Alzheimer disease (AD) vs nondemented individuals. N-terminal heterogeneity can affect the aggregation, toxicity, and stability of Abeta. The human, polar bear, and dog brain share an identical Abeta amino acid sequence. Tissues were immunostained using affinity-purified polyclonal antibodies specific for the L-aspartate residue of Abeta at position one (AbetaN1[D]), D-aspartate at N1 (AbetaN1[rD]), and pyroglutamate at N3 (AbetaN3[pE]) and p3, a peptide beginning with leucine at N17 (AbetaN17[L]). The results demonstrate that each Abeta N-terminal isoform can be present in diffuse plaques and CVA deposits in AD brain, nondemented human, and the examined aged animal models. Though each Abeta N-terminal isoform was present in diffuse plaques, the average amyloid burden of each isoform was highest in AD vs polar bear and dog (beagle) brain. Moreover, the ratio of AbetaN3(pE) (an isoform that is resistant to degradation by most aminopeptidases) vs AbetaN17(L)-x (the potentially nonamyloidogenic p3 fragment) was greatest in the human brain when compared with aged dog or polar bear. Neuritic plaques in AD brain typically immunostained with antibodies against AbetaN1(D) and AbetaN3(pE), but not AbetaN17(L) or AbetaN1(rD). Neuritic deposits in nondemented individuals with atherosclerotic and vascular hypertensive changes could be identified with AbetaN1(D), AbetaN3(pE), and AbetaN1(rD). The presence of AbetaN1(rD) in neuritic plaques in nondemented individuals with atherosclerosis or hypertension, but not in AD, suggests a different evolution of the plaques in the two conditions. AbetaN1(rD) was usually absent in human CVA, except in AD cases with atherosclerotic and vascular hypertensive changes. Together, the results demonstrate that diffuse plaques, neuritic plaques, and CVA deposits are each associated with distinct profiles of Abeta N-terminal isoforms.
Aged↗
Familial influence on plaque formation in the beagle brain.
Aged canines exhibit central neuropathological changes strikingly similar to those seen in patients with Alzheimer's disease. In this study, brain tissue from pure bred beagles raised in a controlled environment were examined for Alzheimer-like pathology. The mean age of the animals was 15.6 years. The incidence of plaques among these 29 dogs was 65.5%. Of the 19 samples that demonstrated Alzheimer-like pathology, 18 were characterized as diffuse and one as neuritic. Plaque density was found to be independent of age. Plaque numbers were highest in the perirhinal cortex and the adjacent temporal cortex. Familial influence on plaque development is supported by congruence within 15 of the 16 litters examined (p < 0.001). In this environmentally controlled group the diffuse plaques were rarely converted to the dense neuritic plaques found in Alzheimer's disease.
Aging↗
Bile acid profiles in peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency.
Fast atom bombardment mass spectrometry and gas chromatography-mass spectrometry were used to analyze bile acids in the body fluids of an infant (L.C.) whose liver contained no immunoreactive peroxisomal 3-oxoacyl-CoA thiolase. The profiles were compared with those of six patients with undetectable peroxisomes (Zellweger syndrome) and two siblings (N.B. and I.B.) whose defect of peroxisomal beta-oxidation could not be localized by morphological studies of peroxisomes or by immunoblotting of peroxisomal beta-oxidation proteins. 3 alpha, 7 alpha, 12 alpha-Trihydroxy-5 beta-cholestan-26-oic acid (THCA) was present in bile and plasma of all patients. However, bile from L.C., N.B. and I.B. contained unconjugated varanic acid (3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta-cholestan-26-oic acid) as the major C27 bile acid, whereas bile from Zellweger patients contained only small amounts of varanic acid. In the bile from L.C. two isomers of varanic acid were present; in the bile from N.B. and I.B. a single isomer predominated. L.C., N.B., and I.B. all produced bile containing small amounts of (24E)-3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-24-en-26-oic acid [( 24E]-delta 24-THCA), its [24Z]- isomer, 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-23-en-26-oic acid and 3 alpha, 7 alpha, 12 alpha-trihydroxy-27-nor-5 beta-cholestan-24-one. The results provide evidence for peroxisomal pathways for cholic acid synthesis in man via THCA, delta 24-THCA and varanic acid and show that bile acid analyses can be used to diagnose peroxisomal thiolase deficiency.
Acetyl-CoA C-Acyltransferase↗
3-Oxo-delta 4 bile acids in liver disease.
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Bile Acids and Salts↗
Carboxy terminal of beta-amyloid deposits in aged human, canine, and polar bear brains.
Immunocytochemistry, using antibodies specific for different carboxy termini of beta-amyloid. A beta 40 and A beta 42(43), was used to compare beta-amyloid deposits in aged animal models to nondemented and demented Alzheimer's disease human cases. Aged beagle dogs exhibit diffuse plaques in the absence of neurofibrillary pathology and the aged polar bear brains contain diffuse plaques and PHF-1-positive neurofibrillary tangles. The brains of nondemented human subjects displayed abundant diffuse plaques, whereas the AD cases had both diffuse and mature (cored) neuritic plaques. Diffuse plaques were positively immunostained with an antibody against A beta 42(43) in all examined species, whereas A beta 40 immunopositive mature plaques were observed only in the human brain. Anti-A beta 40 strongly immunolabeled cerebrovascular beta-amyloid deposits in each of the species examined, although some deposits in the polar bear brain were preferentially labeled with anti-A beta 42(43). beta-amyloid deposition was evident in the outer molecular layer of the dentate gyrus in the aged dog, polar bear, and human. Within this layer, A beta 42 was present as diffuse deposits, although these deposits were morphologically distinct in each of the examined animal models. In dogs, A beta 42 was cloud-like in nature; the polar bear demonstrated a more aggregated type of deposition, and the nondemented human displayed well-defined deposits. Alzheimer's disease cases were most frequently marked by neuritic plaques in this region. Taken together, the data indicate that beta-amyloid deposition in aged mammals is similar to the earliest stages observed in human brain. In each species, A beta 42(43) is the initially deposited isoform in diffuse plaques.
Aged↗
Determination of water in forages and animal feeds by Karl Fischer titration.
Oven methods for determining moisture (volatiles) in forages and other animal feeds are empirical. The moisture concentration obtained depends upon the time and temperature the sample was dried and is influenced by the presence of other volatiles than water. A validated reference method to measure water in forages and animal feeds could be used to evaluate the appropriateness of oven methods for various types of animal feeds and forages. Karl Fischer titration is a well-established method for determining water. However, thorough extraction of water from forages and feeds is a challenge because they often contain cellular structures that release water slowly. Water was successfully extracted into methanol-formamide (50 + 50) by high-speed homogenization and then titrated directly at 50 degrees C with a one-component Karl Fischer reagent based on imidazole. The method is described in detail, results of day-to-day repeatability and laboratory-to-laboratory reproducibility are reported, and preliminary comparison data between oven methods are provided.
Analysis of Variance↗