Psoriasin expression in mammary epithelial cells in vitro and in vivo.

We determined, by serial analysis of gene expression (SAGE) analysis of normal and DCIS (ductal carcinoma in situ) mammary epithelial cells, that psoriasin and several other genes implicated in psoriasis are aberrantly expressed in high-grade, comedo DCIS. Real-time PCR, mRNA in situ hybridization, and immunohistochemical analysis of breast carcinomas confirmed that psoriasin is frequently overexpressed in estrogen receptor-negative tumors. To gain insight into regulatory pathways that control psoriasin expression, we developed polyclonal and monoclonal antibodies and investigated mechanisms that may account for elevated levels of psoriasin in DCIS. Here, we report that loss of attachment to extracellular matrix, growth factor deprivation, and confluent conditions dramatically up-regulate psoriasin expression in MCF10A mammary epithelial cells. All of these conditions are characteristic of high-grade DCIS and psoriatic skin lesions; therefore, the same mechanisms may be responsible for increased expression of psoriasin in vitro and in vivo.     

Genetic basis of primary hyperoxaluria type II

Primary hyperoxaluria Type II (PH2) is a rare monogenic disease characterized by excessive urinary oxalate and L-glycerate excretion. The severity of clinical complications in PH2 patients can range from none to end-stage renal failure secondary to massive deposits of calcium oxalate crystals in the kidney. The disease is a result of the absence of an enzyme with glyoxylate reductase and hydroxypyruvate reductase activities (GRHPR). Recent breakthroughs have occurred in our understanding of the molecular basis of PH2. In this article, we briefly review the literature concerning the clinical and biochemical characteristics of the disease and the enzyme associated with it. We describe the identification of the cDNA for the GRHPR enzyme using the expressed sequence tag database, the characterization of the human GRHPR gene, and the identification of mutations in patients with PH2. Insights gained from the molecular biology underlying this disease as they relate to relevant clinical issues such as potential therapeutic strategies are discussed.     

Event-related brain potentials (ERPs) in schizophrenia for tonal and phonetic oddball tasks.

BACKGROUND: Prior studies using simple target detection ("oddball") tasks with pure tones have reported asymmetric reduction of the P3 event-related potential (ERP). This study investigated the time course and topography of ERPs recorded during both tonal and phonetic oddball tasks. METHODS: Event-related potentials of 66 patients (14 unmedicated) diagnosed with schizophrenia (n = 46) or schizoaffective disorder (n = 20) and 32 healthy adults were recorded from 30 scalp electrodes during two oddball tasks using consonant-vowel syllables or complex tones. Overlapping ERP components were identified and measured by covariance-based principal components analysis. RESULTS: Schizophrenic patients showed marked, task-independent reductions of early negative potentials (N1, N2) but not reduced P3 amplitude or abnormal P3 asymmetry. Task-related hemispheric asymmetries of the N2/P3 complex were similar in healthy adults and schizophrenic patients. Poorer task performance in patients was related to ERP amplitudes, but could not account for reductions of early negativities. CONCLUSIONS: The findings suggest that both patients and control subjects activated lateralized cortical networks required for pitch (right frontotemporal) and phoneme (left parietotemporal) discrimination. Task-independent reductions of negativities between 80 and 280 msec after stimulus onset suggest a deficit of automatic stimulus classification in schizophrenia, which may be partly compensated by later effortful processing.     

Radiological features of a symptomatic splenic hamartoma

Symptomatic splenic hamartomas are rare in the pediatric age group, with only four previous reports in the literature. Splenic hamartoma has been reported as a solid homogeneous mass without calcification on CT and ultrasound (US), and only one previous report of the findings on MRI has been published. We report a case of a large symptomatic splenic hamartoma in a 14-year-old girl who presented with splenomegaly, pancytopenia and growth retardation. A solid mass with multiple punctate foci resembling calcifications was seen on US. The mass was heterogeneous and better demarcated on enhanced CT. Radiocolloid scintigraphy demonstrated uptake within the lesion, but less than that of normal spleen. The mass was isointense relative to normal splenic tissue on T1-weighted MRI (0.5 T) and of increased intensity with T2 weighting. At splenectomy, a red pulp hamartoma was identified, which contained nodules of hyalinization and necrosis thought to account for the punctate foci seen on US.     

Self-image as a Predictor of Outcome in Adolescent Major Depressive Disorder

Abstract— We investigated the ability of a measure of self-image, two measures of depression, and demographic characteristics to predict the outcome of depressive symptoms. Subjects were 47 adolescents who were referred to outpatient treatment for depression. Subjects were assessed for depressive symptoms at three time periods. Self-image as measured by the Offer Self-image Questionnaire (OSIQ) was a significant predictor of depressive symptoms at both 3 months and 1 year. That was independent of initial levels of depression. The two most predictive scales from the OSIQ, were the emotional tone and mastery of the external world scales. The results are consistent with previous research indicating the importance of self-image in adolescent depression The implications of these findings for treatment of adolescent depression are discussed.     

Right heart pressure determination by Doppler in infants with tricuspid regurgitation

Doppler and direct measurements of right ventricle to right atrial pressure drop were made during cardiac catheterisation on 28 occasions in 26 infants with congenital heart disease. Age was 10 days to 12 months (median 4.5 months), and weight was 3.1 to 9.0 kg (median 4.7 kg). We measured peak velocity of tricuspid regurgitation by continuous wave Doppler, and the pressure drop was calculated using the modified Bernoulli equation (delta p = 4v2). There was a high correlation (r = 0.95) between direct and Doppler measurements. Doppler values tended to underestimate the right ventricle to right atrial pressure drop, but this was not of clinical significance (mean 2 mm Hg). The 95% confidence interval for the Doppler velocity was -0.41 to +0.26 m/sec, and was consistent across the range of pressures studied. Variability between observers was tested, by two observers performing sequential paired examinations on 16 newborn babies with tricuspid regurgitation. The coefficient of repeatability was 6.3 mm Hg (95% confidence interval 4.7 to 9.5 mm Hg) or 0.26 m/sec (0.18 to 0.50 m/sec). This method of right ventricular pressure estimation, validated previously only in older children and adults, is a reproducible and accurate technique in infants with tricuspid regurgitation.     

Prostate mutations in rats induced by the suspected human carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Male lacl transgenic rats were fed a diet containing 200 ppm of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine present in cooked meats. PhIP was found to be a powerful prostate mutagen. After 61 days of treatment, the lacl mutant frequency was 71 x 10(-5), >20-fold higher than the spontaneous mutant frequency of 3.2 x 10(-5). The predominant PhIP-induced mutations were G:C->T:A transversions and deletions of G:C bp. The results directly link PhIP-induced mutations with the earlier observation of PhIP-induced prostate cancer in rats and suggest that exposure to dietary PhIP could be a risk factor in the incidence of human prostate cancer.