Structural and immunologic characteristics of subviral components of Sindbis, eastern equine and western equine encephalitis viruses.
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Biomedical subjects
Publications and source records attributed to R Ravid.
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The effect of short-term treatment with diphenylhydantoin (DPH) on the insulin secretion patterns during OGTT and on the daily insulin profile was studied in obese patients. DPH treatment for 3 days with a dose of 300 mg/die (100 mg, 3 times daily) significantly decreased the insulin release after glucose ingestion, but did not alter the basal insulin level. No effect on the fasting glucose concentration as well as on the glucose profiles during OGTT was observed after short-term DPH treatment. A smaller decrease of plasma free fatty acid concentration during OGTT performed after DPH administration confirmed the inhibitory effect of the drug on insulin release. Short-term DPH treatment was also shown to decrease markedly the postpradial insulin release in obese patients. No difference was noted between plasma 11-OHCS and serum HGH concentrations during OGTT before and after DPH treatment. The possible therapeutic role of DPH in obesity is discussed.
It has been hypothesized that Alzheimer's disease (AD) is caused by an accumulation of damage in DNA due to defective DNA-repair (21). Attempts to test this hypothesis by determining the activity of DNA-repair systems in nonneuronal cells from AD patients and controls so far provided conflicting results. An alternative approach is the direct comparison of DNA-damage levels in neuronal tissue of AD patients and controls. In the present study we assayed the level of DNA breaks and alkali-labile sites in cerebral cortex tissue samples from AD patients and controls obtained from rapid autopsies. Our data on 11 AD patients and 8 control subjects indicate an at least two-fold higher level of DNA damage in cortex of AD patients as compared to controls.
The earlier described age-related decreases in vasopressin innervation of extra-hypothalamic rat brain regions were found to coincide with a decrease in vasopressin expression in the cells where these fibers originated. A significant age-related decrease in the number of vasopressin-immunoreactive cell bodies was found in the medial amygdala and locus coeruleus of senescent Brown-Norway (BN/BiRij) rats (33 months) when compared to middle-aged (19 months) and young (3 months) rats. In addition, total testosterone plasma levels were significantly reduced in middle-aged and old rats as compared to young animals and the number of vasopressin-immunoreactive cells in both the medial amygdala and locus coeruleus correlated significantly with the decreased testosterone levels in a similar way as found earlier for vasopressin terminals.
Accumulation of oxidative DNA damage has been proposed to underlie aging and neurodegenerative diseases such as Alzheimer's Disease (AD). The DNA adduct 8-hydroxy-2'-deoxyguanosine (8OHdG) is considered a good indicator of oxidative DNA damage. To investigate whether this type of DNA damage is involved in AD etiology, 8OHdG levels were determined in postmortem human brain tissue of controls and AD patients (in frontal, occipital, and temporal cortex and in hippocampal tissue). Parametric studies in rat revealed no influences of postmortem delay, repeated freezing/thawing or storage time. In human brain, approximately two 8OHdG molecules were present per 10(5) 2'-deoxyguanosines. In AD patients and controls, 8OHdG-levels were not related to age, sex, or brain region. Also, no differences were found between controls and AD patients. It was concluded that 8OHdG in nuclear DNA, although present throughout the brain in fairly high amounts, does not accumulate with age, nor does it appear to be involved in AD. More detailed studies are required to extend this conclusion to other types of oxidative damage.
Phosphatidylinositol kinase (PI kinase) and phosphatidylinositol phosphate kinase (PIP kinase) were assayed in a membrane-free cytosolic fraction prepared from the medial temporal cortex of patients with Alzheimer's disease (AD) and nondemented controls, with exogenous lipids as substrate. 32P-PIP formation appeared to be reduced by 21% in patients with AD who died before 80 years, compared to matched controls. In addition, there was an age-related decrease in PI kinase activity in the control group. In the AD patients there was no age-related decrease. Very old AD patients (older than 80 when they died) with a short duration of the disease were characterized by increased PI kinase activity. No differences were found in the closely related enzyme PIP kinase. The results are indicative for heterogeneity in AD.
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The pineal hormone melatonin is involved in physiological transduction of temporal information from the light dark cycle to circadian and seasonal behavioural rhythms, as well as possessing neuroprotective properties. Melatonin and its receptors MT1 and MT2, which belong to the family of G protein-coupled receptors, are impaired in Alzheimer's disease (AD) with severe consequences to neuropathology and clinical symptoms. The present data provides the first immunohistochemical evidence for the cellular localization of the both melatonin receptors in the human pineal gland and occipital cortex, and demonstrates their alterations in AD. We localized MT1 and MT2 in the pineal gland and occipital cortex of 7 elderly controls and 11 AD patients using immunohistochemistry with peroxidase-staining. In the pineal gland both MT1 and MT2 were localized to pinealocytes, whereas in the cortex both receptors were expressed in some pyramidal and non-pyramidal cells. In patients with AD, parallel to degenerative tissue changes, there was an overall decrease in the intensity of receptors in both brain regions. In line with our previous findings, melatonin receptor expression in AD is impaired in two additional brain areas, and may contribute to disease pathology.