Cellular and molecular regulation of serotonin N-acetyltransferase activity in chicken retinal photoreceptors

Serotonin N-acetyltransferase (AA-NAT; arylalkylamine N-acetyltransferase; EC 2.3.1.87) is the penultimate enzyme in melatonin synthesis and large changes in the activity of this enzyme appear to regulate the rhythm in melatonin synthesis. Recent advances have made it possible to study the mRNA encoding chicken AA-NAT, which has only been detected in the retina and pineal gland. Within the retina, AA-NAT mRNA is expressed primarily in photoreceptors. The levels of chicken retinal AA-NAT mRNA and activity exhibit 24-hour rhythms with peaks at night. These rhythms appear to reflect circadian clock control of AA-NAT mRNA abundance and independent effects of light and darkness on both mRNA levels and enzyme activity. The effects of darkness and light may occur through alterations in cAMP-dependent protein phosphorylation, which increases AA-NAT activity in photoreceptor cell cultures. The cAMP-dependent increase of AA-NAT enzyme activity reflects, at least in part, increased mRNA levels and inhibition of enzyme inactivation by a posttranslational mechanism. This review discusses a hypothetical model for the cellular and molecular regulation of AA-NAT activity by circadian oscillators and light in chicken retinal photoreceptor cells.     

Reanalysis of the National Institute of Mental Health Treatment of Depression Collaborative Research Program General Effectiveness Report

The National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program General Effectiveness Report statistical analyses are criticized. Their analyses, which fostered the belief that criticized. Their analyses, which fostered the belief that the active treatments were indistinguishable, were compromised by an inappropriately stringent level of significance with regard to both heterogeneity of slope and pairwise group differences. Once slope heterogeneity is detected, the Johnson-Neyman technique is more appropriate than arbitrary sample subdivision. All of these tactics lowered power substantially. Our reanalysis indicates a reasonable ordering for the treatments with medication superior to the psychotherapies and the psychotherapies somewhat superior to placebo. These effects are particularly marked among the more symptomatic and impaired patients. The lack of dosage by severity analyses renders the severity findings ambiguous. Scientific and public health implications are discussed.     

MR of spinal cord ganglioglioma

PURPOSE: Our purpose was to describe the MR imaging features in a series of spinal intramedullary gangliogliomas and to compare these findings with the MR features of intramedullary astrocytomas and ependymomas. METHODS: A retrospective analysis was performed of 76 MR examinations in 27 patients with histologically proved spinal ganglioglioma; these were then compared with imaging findings in a representative sample of histologically proved spinal cord astrocytomas and ependymomas. RESULTS: Statistically significant observations regarding spinal gangliogliomas included young age of the patients (mean, 12 years), long tumor length, presence of tumoral cyst, presence of bone erosion and scoliosis, absence of edema, presence of mixed signal intensity on T1-weighted images, and presence of patchy enhancement and cord surface enhancement. A trend (not statistically significant) was noted for holocord involvement and lack of magnetic susceptibility. CONCLUSION: Spinal ganglioglioma can be strongly suspected if MR images reflect the above criteria; however, the ultimate diagnosis still depends on radical resection and appropriate histopathologic investigation.     

Deficient muscle carnitine transport in primary carnitine deficiency

The effects of conditions that either increase or decrease heart rate on the pharmacological properties of adenosine receptors in cultured rat myocytes were examined. Levels of A1 adenosine receptors, following prolonged treatment with electrical stimulation (ES) or the antiarrhythmic drug amiodarone, were determined using radioligand binding with the specific A1 receptor antagonist [3H]1,3-dipropyl-8-cyclopentylxanthine (CPX). The effects of lowering temperature were also explored. Exposure to amiodarone for 4 days reduced the density of A1 receptors by 19% (from 24.7 +/- 0.4 to 20.09 +/- 0.3 fmol/dish) and inhibited the rate of contraction by 60% (from 188 +/- 16 to 76 +/- 30 beats/min), without changing the receptor affinity, protein content, creatine kinase (CK) activity or cell number. Electrical stimulation at 25 degrees C elevated the density of A1 adenosine receptors by 185% (from 4.1 +/- 0.4 to 11.69 +/- 2.1 fmol/dish). Four days of reduced temperature (from 37 degrees C to either 30 or 25 degrees C) lowered the density of A1 adenosine receptors by 69 or 86%, respectively (from 24.1 +/- 1.2 to 7.4 +/- 0.4 or 3.4 +/- 0.3 fmol/dish), with no significant change in the receptor affinity, activity of CK, or lactate dehydrogenase (LDH), protein content or cell number. The observed up- and down-regulation of A1 adenosine receptors in primary myocyte cultures in response to conditions that exogenously alter the rate of contraction, is indicative of the role of adenosine receptors in adaptation of heart cells to stress.     

Adult and neonatal anti-Gal response in knock-out mice for alpha1,3galactosyltransferase

The hypothalamus-pituitary-adrenal axis of the sheep fetus plays a critical role in fetal development, responsiveness to stress, and initiation of parturition. We have recently reported that the fetal lung contains and secretes significant amounts of immunoreactive adrenocorticotropin (iACTH). The present study was designed to identify the molecular weight profile and the cellular location of iACTH in this tissue. iACTH extracted from fetal lung was immunoprecipitated, electrophoresed, and immunoblotted. Pulmonary iACTH was found in several molecular forms. The largest peptides appeared as doublets, and had molecular weights similar to POMC (32, 33 kD). Smaller peptides appeared in molecular weights (17, 24, and 27 kD) which were not consistent with the post-translational processing of POMC in fetal pituitary, but which were consistent with known processing of POMC by chromaffin granule aspartyl protease. None of the molecular forms of iACTH were glycosylated. Immunohistochemistry revealed that the iACTH was contained within bronchial epithelium and within groups of cells within the parenchyma of the lung. Both of these types of cells are consistent with pulmonary neuroendocrine cells. The distribution of neuroendocrine cells and apparent concordance with the iACTH-positive cells was confirmed by immunostaining for neuron specific enolase, a marker for neuroendocrine cells within the lung. We conclude that the lung contains unprocessed and partially processed POMC within cells known to contain neuropeptides. We speculate that secretion of the POMC-related peptides from these cells is physiologically important in the late-gestation fetus.     

Loss of heterozygosity and loss of expression of the DCC gene in gastric cancer

Even with a good surveillance program, nosocomial infections may be not recognized because of several reasons: absence of symptoms or prolonged incubation period (eg, viral bloodborne infections, tuberculosis); problems with the microbiological diagnosis, because adequate specimens may be difficult to obtain or special methods should be used (eg, fungal infections, virus, new agents); shorter hospital stays (eg, surgical-site infections); difficulty in distinguishing between nosocomial and community-acquired infections (eg, influenza); and failure to detect clinically relevant colonization (eg, multiresistant microorganisms). Because of the important potential consequences of occult nosocomial infections, specific surveillance programs should be designed to address these problems.