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.     

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.     

An investigation into the effects of structured music workshops with adults with mental handicap

This study investigated the effects of structured group workshops for a population with special needs. Twenty subjects, each with a mild or moderate mental handicap, attended a series of 10 weekly 1-hour music workshops on the structured group playing of a Javanese Gamelan. Twenty subjects formed a non-intervention control group. The experimental hypothesis was that participation in the experimental group would produce significant improvements in musical ability as measured by the Rossi test of musical ability, devised and validated for use in this study. Significant gains in communication skills as measured by the Communication Assessment Profile for Adults with a Mental Handicap (CASP) and self-esteem levels measured by the Khalid semantic differential technique were also postulated. It was also suggested that these gains would be significantly correlated. Results show significant gains in musical ability (instrumental rhythm production: t = 5.67, d.f. = 29, p < 0.01 and simple rhythm production: t = 8.42, d.f. = 29, p < 0.01) and communication skills (t = 4.69, d.f. = 29, p < 0.01). Moreover these results are significantly correlated (r = 0.59, p < 0.05, r = 0.75, p < 0.05, r = 0.56, p < 0.05). A ceiling effect was obtained in the measurement of self-esteem. It is suggested that these gains derive from certain aspects of the musical communicative environment at the workshops. Suggestions for future research involve examining the possible influences on these developments.     

A pocket-calculator algorithm for the shapiro-francia test for non-normality: An application to medicine

An easy-to-calculate approximation to the Shapiro—Francia W' test and its P-value is proposed. Its accuracy is sufficient for practical application in samples of size 5 or larger.     

Multiple sclerosis and headache co-morbidity. A case-control study

The prevalence of primary headache (PH) in a multiple sclerosis (MS) sample vs. control healthy subjects was investigated at a neurological clinic in 2004–2005: 122 of 238 (51%) MS patients and 57 of 238 (23%) controls proved to be affected by headache. The groups did not differ for the rates of PH types. Headache types of MS patients were comparable to those of PH patients that were observed at the same institute in a case-control comparison. First symptoms of headache preceded those of MS in two thirds of cases. Headache features did not significantly change after MS onset. Comorbidity of MS and PH could be explained by some common clinical and biological traits.     

Definition of An Optimal First-line Chemotherapy in Metastatic Breast Cancer

Single-agent chemotherapy of metastatic breast cancer is the treatment of choice in patients with slow tumor progression and asymptomatic disease. In this patient group, the choice of drugs is based more on good tolerability than on efficacy. By contrast, symptomatic or rapidly progressing disease requires the use of highly active regimens where more weight is put on reliable antitumor activity. While anthraycline-based combination regimens have set the standard of effective treatment, the addition of docetaxel (and to a lesser extent paclitaxel) has improved tumor response, but failed to induce a consistent prolongation of survival. Based on retrospective analyses, it is hypothesised that the combined use of anthracyclines and taxanes in first-line therapy may be most beneficial in defined subgroups: after adjuvant chemotherapy, in patients with HER-2 gene amplification, possibly also in patients with rapidly progressing visceral disease.