Stereologic assessment of the total cortical volume occupied by amyloid deposits and its relationship with cognitive status in aging and Alzheimer's disease.

Although the presence of amyloid deposits is required to establish the neuropathologic diagnosis of Alzheimer's disease, from a clinical point of view, a direct contribution of these cerebral lesions to cognitive deficits is still controversial. The development and standardization of quantitative and accurate biochemical and neuropathologic methods may be critical to improve the postmortem diagnosis and clinicopathologic correlations. Here, we used a point counting method, based on the Cavalieri principle, to estimate the volume occupied by amyloid deposits in a discrete region of the prefrontal cortex and in the hippocampal formation, in brains from patients with cognitive status ranging from normal to severely demented. We demonstrate that the assessment of the total volume occupied by the amyloid deposits in the entorhinal cortex and subiculum can be considered an effective predictor of dementia severity. We also reveal the existence of a high degree of regional and interindividual heterogeneity in amyloid distribution and relative volume. Our data suggest that even though a correlation was observed between the stereologic point counting method and a non-stereologic random field thresholding approach, in most cases non-stereologic methods may not provide adequate samples of the tissue and may lead to unreliable estimates of amyloid burden due to the inhomogeneous distribution of amyloid in the cerebral cortex and the large variability among brains.

Herbal medicine for the treatment of cardiovascular disease: clinical considerations.

Herbs have been used as medical treatments since the beginning of civilization and some derivatives (eg, aspirin, reserpine, and digitalis) have become mainstays of human pharmacotherapy. For cardiovascular diseases, herbal treatments have been used in patients with congestive heart failure, systolic hypertension, angina pectoris, atherosclerosis, cerebral insufficiency, venous insufficiency, and arrhythmia. However, many herbal remedies used today have not undergone careful scientific assessment, and some have the potential to cause serious toxic effects and major drug-to-drug interactions. With the high prevalence of herbal use in the United States today, clinicians must inquire about such health practices for cardiac disease and be informed about the potential for benefit and harm. Continuing research is necessary to elucidate the pharmacological activities of the many herbal remedies now being used to treat cardiovascular diseases.

Novel and frequent mutations of hepatitis B virus coincide with a major histocompatibility complex class I-restricted T-cell epitope of the surface antigen.

We examined the full-length hepatitis B virus (HBV) envelope (surface antigen or HBV small surface antigen [HBsAg]) sequences of 12 different liver samples from 10 different hepatoma-containing chronic carriers. Surprisingly, novel and frequent mutations occurred predominantly at amino acids 40 and 47 of HBsAg, in addition to within a known protective B-cell epitope (so-called group a determinant of HBsAg 124-148). Approximately 58% of chronic carriers contain mutations at the group a determinant. The mutation frequency at the hotspot codons 40 and 47 is approximately 83%, 1 order of magnitude higher than at the known polymorphic sites of subtype-specific determinants at codons 122 and 160, which is approximately 4%. This new mutational domain is found to coincide with a major histocompatibility complex class I-restricted T-cell epitope. The potential biological significance of this novel mutation in the immunopathogenesis of HBV chronic carriers is discussed.