Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypothalamic lateral tuberal nucleus was investigated in 5 young patients, aged 45 to 64 years, with Alzheimer's disease (AD) and in 5 age-matched control subjects. Combining conventional histopathological and immunocytochemical staining with neuronal counts, a peculiar form of neuronal pathology was characterized. Although neurons and neurites in the lateral tuberal nucleus of AD specimens were heavily stained by Alz-50, silver and thioflavine-S stains disclosed few neurofibrillary tangles or neurites. The numbers of neurons in the lateral tuberal nucleus of patients with AD (67,450; SEM = 5,050) were no different from those of control subjects (58,900; SEM = 2,450). In the AD patients, few plaques were present and were almost exclusively of the amorphous variety. We conclude that neurons in the lateral tuberal nucleus show an early stage of AD-related cytoskeletal pathology (Alz-50 positivity), but without plaques or neuronal death.
 ...
PMID:The hypothalamic lateral tuberal nucleus in Alzheimer's disease. 171 Apr 33

Cerebrospinal fluid (CSF) from 20 male patients with nonneurologic disease (age 64.5 +/- 2.8 SEM) was analyzed for the presence of the serpin alpha 1-antichymotrypsin (alpha 1-ACT). A chymotrypsin-specific chromogenic substrate (succinyl-Ala-Ala-Pro-Phe-p-nitroanilide) was used to examine the CSF samples. All CSF samples showed inhibitory activity ranging from 45 to 80% inhibition. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the samples revealed the presence of a 68-kDa protein migrating identical to authentic human plasma alpha 1-ACT. Complex formation was performed with iodinated bovine chymotrypsin for several representative CSF samples having the highest chymotrypsin inhibitory activity. Comparison was made with complex formation performed with commercially available authentic human plasma alpha 1-ACT. These studies showed the formation of complexes at 37 degrees C, regardless of whether the sample was subsequently boiled or not. In the case of CSF, two complex bands, mass smaller than with plasma alpha 1-ACT, were formed at the lower temperature whereas a single higher Mr band was formed when the samples were boiled. To determine whether cleavage of the serpin occurred, these studies were repeated using human neutrophil cathepsin G as target protease. A complex of approximately 90 kDa was formed with human alpha 1-ACT under these same conditions. alpha 1-ACT has been detected in senile amyloid plaques in brains of Alzheimer's disease patients, the only plasma serine protease inhibitor localized to these structures. Another serpin, protease nexin I, is also found in these plaques, but this inhibitor does not circulate in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Characterization of the serpin, alpha 1-antichymotrypsin, in normal human cerebrospinal fluid. 172 48

The plasma distribution of gallium (as an analogue of aluminium) was investigated in patients with Alzheimer disease, Down syndrome, or stroke dementia, in subjects on haemodialysis for chronic renal failure, and in healthy controls. Gallium-transferrin binding was significantly lower in the Alzheimer (mean [SEM] 7.9 [1.1]%) and Down syndrome groups (6.9 [0.7]%) than in the controls (17.1 [1.6]%), whereas stroke dementia and haemodialysis patients had normal binding. There were no differences among the groups in plasma citrate concentration. The plasma transferrin concentration was slightly lower in the Alzheimer and Down syndrome groups than in the controls, but even lower in stroke dementia patients (1.74 [0.14] g/l vs 2.98 [0.18] g/l in controls). Transferrin iron saturation was higher in the Alzheimer (58.9%) and Down syndrome groups (81.6%) than in the controls (39.0%) or stroke dementia patients (33.4%). This deficiency of gallium/aluminium binding would leave more unbound aluminium which could move readily into the brain, where it has neurotoxic effects.
 ...
PMID:Defective gallium-transferrin binding in Alzheimer disease and Down syndrome: possible mechanism for accumulation of aluminium in brain. 197 9

The number of Thioflavine S-positive neurofibrillary tangles (NFT) and neuritic plaques (NP) was determined in visual and auditory cortical regions of 8 patients with Alzheimer's disease. On both a regional and laminar basis, NFT exhibited very distinctive and consistent distribution patterns. The mean (+/- SEM) number of NFT in a 250-micron-wide cortical traverse was very low in area 17, primary visual cortex (0.9 +/- 1.0), increased 20-fold in the immediately adjacent visual association cortex of area 18 (19.7 +/- 3.6), and showed a further doubling in area 20, the higher-order visual association cortex of the inferior temporal gyrus (35.5 +/- 8.8). Similar differences in NFT number were present between primary auditory (1.6 +/- 0.5) and auditory association (18.9 +/- 5.4) regions. On a laminar basis, NFT were predominantly present in layers III and V, although there were striking regional differences in the proportion of NFT in these 2 layers. Layer III contained 79% of the NFT in layers III and V in area 18, 41% in area 20, and only 27% in area 22. In contrast, NP showed different, and less specific, regional and laminar distribution patterns. Total NP number was similar in the 3 visual areas, although there were marked regional differences in the type of NP present. Nearly 80% of the NP in area 17 was of the NPc type (i.e., contained a dense, brightly fluorescent core), whereas over 70% of the NP in both areas 18 and 21 was of the NPnc type (i.e., lacked a dense, brightly fluorescent core). NP were present in every cortical layer but were most numerous in layers III and IV. The distinctive distribution patterns of NFT are very similar to the regional and laminar locations of long corticocortical projection neurons in homologous regions of monkey neocortex. This association suggests that NFT reside in the cell bodies of a subpopulation of pyramidal neurons, namely, those that furnish long corticocortical projections. In contrast, the distribution patterns of NP suggest that multiple neuronal systems contribute to their formation.
 ...
PMID:Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual and auditory cortices. 243 65

The clinical pharmacokinetics of tacrine hydrochloride have been characterized in patients who have Alzheimer's disease. Serum concentrations of the drug and of its probable metabolite were monitored in eight patients after a 25 mg oral dose, in six patients after a 50 mg oral dose, in four patients after repeated administration of 50 mg, and in two patients after a small intravenous dose. Urinary excretion of drug and metabolite for 24 hours was measured in one of the patients who received a small intravenous dose. The serum half-life was 1.59 +/- 0.15 hours (mean +/- SEM) after the 25 mg dose, 2.14 +/- 0.24 hours after the 50 mg dose, and 2.91 +/- 0.39 hours after continuous treatment. After intravenous administration, clearance was above 600 ml/min in both patients, and oral bioavailability was calculated at below 5%. Urine recovery was less than 3% of the dose. The low bioavailability of tacrine hydrochloride is partly explained by presystemic metabolism.
 ...
PMID:Pharmacokinetics of tacrine hydrochloride in Alzheimer's disease. 259 67

As a test of the significance of previously described biochemical abnormalities in thiamine-dependent enzymes in brains and other tissues in patients with Alzheimer's disease, a double-blind, placebo-controlled, crossover, outpatient pilot study compared the effects of 3 g/d of oral thiamine hydrochloride for three months with those of a niacinamide placebo. Eleven moderately impaired patients with "probable Alzheimer's disease" by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria completed the study. All patients were well nourished and had no stigmata of dietary thiamine deficiency. Their initial mean +/- SEM Mini-Mental State Examination score was 14.2 +/- 1.4, and the mean age was 72 years. Global cognitive rating by the Mini-Mental State Examination was higher during three months with 3 g/d of oral thiamine hydrochloride than with niacinamide placebo. Behavioral ratings, however, did not differ significantly, nor did clinical state when it was judged subjectively.
 ...
PMID:Thiamine and Alzheimer's disease. A pilot study. 296 32

Longitudinal studies of subjects with autopsy-proven Alzheimer's disease in one skilled nursing home and of clinically diagnosed cases (NINCDS/ADRDA criteria) in three community cohorts are compared with regard to the annual rate of change in the error score of the Blessed information-memory-concentration test (IMC) in which the maximum number of errors possible is 33. The four cohorts differed significantly from each other in regard to age, education, sex, and the degree of dementia as measured by the initial IMC score. Subjects spanned the age range of 52 to 96 years and had 2 to 20 years of education. The rate of change in error score per year was similar whether the initial error score was 0 to 7, 8 to 15, or 16 to 23; however, the rate was reduced when the initial error score was 24 or above, due to a ceiling effect of the test. Among subjects with initial IMC scores less than 24, the annual rate of change varied considerably. However, the mean annual rate of change, 4.4 errors (SD +/- 3.6, SEM +/- 0.3) per year, was independent of residence in a nursing home, location of the study site, and of the patient's sex or education. Of particular importance was the finding that the rate of change in mental test score was independent of age. It can be concluded that the rate of cognitive deterioration in patients with Alzheimer's disease is quite variable among individuals and is independent of the patient's age and whether the patient resides in the community or in a nursing home.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Comparison of rate of annual change of mental status score in four independent studies of patients with Alzheimer's disease. 322 73

To determine the prevalence of unrecognized brain dysfunction accompanying chronic severe cardiac disease, we examined 20 clinically stable consecutive admissions to a cardiac rehabilitation service who were free of known stroke or dementia. Age range was 47 to 85 years (mean +/- SEM, 72.5 +/- 2.1 years), the male: female ratio was 10:10. Multiple cognitive deficits including significant memory impairment and disorientation were present in eight patients (40%), and seven of these eight patients were unable to administer their own medications reliably. An additional six patients (30%) showed milder impairments. One patient was found to be normal after neurological examination, four showed evidence of a single brain lesion, and 15 of 20 (75%) had multiple neurological abnormalities suggesting multifocal brain disease. The mechanism of cognitive deficits in cardiac patients is unclear, and it may be related to multiple infarcts, or acute or chronic hypoxic damage secondary to arrhythmias, cardiac failure, or small vessel disease of the brain. The term "circulatory dementia" is proposed to describe patients with vascular disease and non-Alzheimer type dementia. Patients with cardiac disease should undergo cognitive screening, as early identification of patients at risk of progressive intellectual loss may allow early use of preventive therapy.
 ...
PMID:Unrecognized cognitive impairment in cardiac rehabilitation patients. 333 26

Many patients with dementia of the Alzheimer type (DAT) have an abnormal sense of smell. I studied 18 mildly demented subjects with DAT between the ages of 60 and 80 years and found them less able to identify five fragrances compared with 26 healthy elderly controls. The mean (+/- SEM) olfactory identification score for demented subjects was 0.3 +/- 0.2 compared with 2.8 +/- 0.2 for controls. When the subjects were given a multiple-choice list of ten items including the test fragrances and five other odors, performance of both demented and normal subjects improved, with a score of 1.8 +/- 0.4 for subjects with DAT and 4.2 +/- 0.2 for controls. The findings suggest that olfactory deficits are a sensitive, although non-specific, indicator of mild DAT.
 ...
PMID:Olfactory deficits as a neurologic sign in dementia of the Alzheimer type. 363 74

With a computerized data base, a data retrieval system, and a computer program using the actuarial method of life-table analysis, we compared survival rates in different subgroups of patients with dementia of the Alzheimer type (DAT; n = 199). Men (n = 71) had a shorter duration of survival than women (n = 128), with 500-day survival (mean +/- SEM) 84 +/- 5% vs. 99 +/- 3%, p less than 0.01; 1000-day survival 49 +/- 10% vs. 96 +/- 8%, p less than 0.001; 50% survival 1000 days vs. 1550 days. Patients younger than 65 years at onset had a decreased relative duration of survival compared with patients over 65 at onset, suggesting a more malignant course. Patients with a longer duration of illness tended to die sooner, but this effect was not statistically significant. The Kahn-Goldfarb mental-status quotient was not a predictor of survival. Patients with high Haycox behavioral score (greater than 20; n = 50), indicating more severe behavioral impairment, had lower survival rates at 500 days than patients with low scores (less than 12; n = 65) (80 +/- 6% vs. 95 +/- 3%, p less than 0.05). Hachinski ischemic score, measuring signs and symptoms of vascular disease, had no correlation with survival. Factors associated with decreased duration of survival in DAT include male sex, presenile onset, and increased severity of behavioral impairment.
 ...
PMID:Factors associated with duration of survival in Alzheimer's disease. 396 40


1 2 3 4 5 6 7 8 Next >>