High-resolution immunophenotyping of subcellular compartments in tissue microarrays by enzyme metallography.

Ultrasensitive bright field in situ hybridization assays using enzyme metallography (EnzMet) have been developed and validated, but little is known regarding the applicability of EnzMet for immunophenotypic detection of protein via IHC. Superior resolution via discrete metallographic deposits offers the potential for enhancing high-resolution immunophenotyping. Using high-complexity tissue microarrays (TMAs), 88 common solid tumors were evaluated by automated EnzMet (Nanoprobes and Ventana). Targets were chosen to assess the ability of EnzMet to specifically localize encoded antigens in the nucleus (estrogen receptor), cytoplasm (cytokeratins), and cytoplasmic membrane (HER2) in TMAs. Results were compared with conventional IHC diaminobenzidine (DAB) immunostaining. There was full concordance between the EnzMet and conventional IHC results. Furthermore, the EnzMet reaction products did not appreciably diffuse, were dense and sharply defined, and provided excellent high-resolution differentiation of cellular compartments in paraffin sections for the nuclear, cytoplasmic, and cell membrane-localized antigens evaluated. The higher density of elemental silver deposited during enzyme metallography permitted evaluation of core immunophenotypes at a relatively low magnification, allowing more tissue to be screened in an efficient manner. This preliminary study shows the utility of using enzyme metallography for high-resolution immunophenotyping in TMAs.     

Orthotopic placement of the dunning R3327 AT-3 prostate tumor in the copenhagen X fischer rat

Orthotopic placement of in vitro propagated Dunning R3327 AT-3 tumor cells resulted in a greater percentage of tumor takes and a two-fold shift in the exponential growth curve compared to flank implantation. The orthotopic tumor appeared to disseminate preferentially to regional lymph nodes, rather than to the lungs which is characteristic of flank tumors. The results suggest an important role of stromal-epithelial interactions in the growth of this tumor. © 1995 Wiley-Liss, Inc.     

Hypolipidemic activity in rodents of phenobarbital and related derivatives

A series of 5-alkyl-5-phenylbarbituric acid analogues were shown to be potent hypolipidemic agents in rats and mice at 20 mg/kg/day. This dose is lower than that required for hypolipidemic activity for clofibrate and nicotinic acid derivatives in rodents and man. These new derivatives reduced both serum cholesterol and triglyceride levels in rodents by either the oral or intraperitoneal route of administration. Previous studies have demonstrated that similar heterocyclic compounds, i.e. cyclic imides, glutarimides and hydantoins are potent hypolipidemic agents in rodents. The barbituric acid derivatives probably interfered with de novo synthesis of cholesterol and fatty acids in the early steps since the agents inhibit the activities of ATP-dependent citrate lyase and acetyl-CoA synthetase. Triglyceride synthesis may be blocked since the agents inhibited the rate limiting enzyme, sn-glycerol-3-phosphate-acyl-transferase. Rat tissue lipids especially cholesterol and triglycerides were reduced after 14 days treatment. Fecal lipids were increased in cholesterol and phospholipid content by selected compounds. The rat serum lipoprotein after 14 days drug administration showed reduced VLDL-cholesterol and HDL-triglyceride contents. The modulation of the lipid content of the serum lipoproteins by the barbituric acids suggest that these agents may be helpful in treating clinical hyperlipidemic disease states.     

Poverty, health services, and health status in rural America

Access to health services for everyone has been a major policy goal in the United States: inequitable access is assumed to lead to inequitable health status, particularly for low-income groups. A sophisticated model of the relation between poverty, health care needs, service use, and health outcomes is used to analyze cross-sectional data on 7,823 adults from 36 rural communities. Improved access and use are helpful, but evidence clearly indicates that combined health and social initiatives will be necessary to reduce inequalities in health status.     

Cutis Marmorata Telangiectatica Congenita Associated with a Double Aortic Arch

Abstract: We report a patient with cutis marmorata telangiectatica with the hitherto unreported anomaly of a double aortic arch. The presence of two major vascular anomalies in this patient may be secondary to a developmental defect of the mesoderm during embryogenesis.     

A six-year follow-up study of smoking habits and microvascular complications in young adults with type 1 diabetes.

One hundred insulin-dependent diabetic patients (age < 45 years, 53 smokers) were followed for six years. The age, duration of diabetes and mean glycated haemoglobin levels, were comparable between the smokers and non-smokers. Microvascular complications (retinopathy and increased urine albumin excretion) were commoner and more severe in the smoking group at six years, particularly in heavy smokers. Of the 45 original smokers reviewed at six years, 12 (27%) had stopped, six of whom had developed microvascular complications. Only two of the ''heavy'' initial smokers, likely to be at most risk, had stopped smoking, and three original non-smokers had started smoking.