Altered turnover and synthesis rates of lung surfactant following thoracic irradiation

Between 2-6 weeks after thoracic irradiation with 10 Gy X rays, when levels of surfactant in the alveoli show the greatest increase, there is a reduction in the rate of radioactivity loss from 3H-choline labeled disaturated phosphatidylcholine from the lung. This indicates a reduced turnover of surfactant. Discrepancies between the halving times for specific activity and for total radioactivity of the disaturated phospholipids suggest that at between 2 and 3 weeks post-irradiation, removal and degradation of surfactant almost ceases, but that synthesis continues normally. However, by 3 weeks post-irradiation, choline-3H incorporation into disaturated phosphatidylcholine suggests that surfactant synthesis is increased about two-fold. The reduced number of macrophages recovered from alveolar lavage between about 2 and 6 weeks post-irradiation may indicate a reason for the lengthened turnover times of surfactant over this period. Nevertheless the stimulated surfactant production that takes place from about 3 weeks onward suggests an additional active response to radiation or to radiation damage by the type II pneumonocytes. These studies confirm that the maximum levels of alveolar surfactant seen at 3 weeks post-irradiation result from a different lung response than that responsible for the increase in surfactant, which occurs within hours of irradiation.     

Family psychoeducation, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. I. One-year effects of a controlled study on relapse and expressed emotion

Relapse rates averaging 41% in the first year after discharge among schizophrenic patients receiving maintenance neuroleptic treatment led to the development of two disorder-relevant treatments: a patient-centered behavioral treatment and a psychoeducational family treatment. Following hospital admission, 103 patients residing in high expressed emotion (EE) households who met Research Diagnostic Criteria for schizophrenia or schizoaffective disorder were randomly assigned to a two-year aftercare study of family treatment and medication, social skills training and medication, their combination, or a drug-treated condition. First-year relapse rates among those exposed to treatment demonstrate a main effect for family treatment (19%), a main effect for social skills training (20%), and an additive effect for the combined conditions (0%) relative to controls (41%). Effects are explained, in part, by the absence of relapse in any household that changed from high to low EE. Only the combination of treatment sustains a remission in households that remain high in EE. Continuing study, however, suggests a delay of relapse rather than prevention.     

Rapid,simple identification of individual osteoblastic cells and their specific products by cell blotting assay

Biochemical and molecular biological studies of osteoblastic cell function and hormonal regulation are frequently confounded by the inherent cellular heterogeneity and phenotypic instability of existing in vitro and in vivo model systems. A new technique (derived from Western blotting or antibody-based detection of protein molecules bound to nitrocellulose paper) is described for identification of individual cells which synthesize osteoblast-specific gene products (bone Gla-protein, type I collagen, and alkaline phosphatase) or produce cAMP in response to parathyroid hormone (PTH) or isoproterenol. Dispersed primary neonatal rat calvariae or osteogenic sarcoma cells were “plated” on Immobilon-P (a hydrophobic transfer membrane with very high protein-binding capacity) for 30 minutes to several hours, followed by agonist treatment, formalin fixation, hematoxylin staining, and immunostaining with a battery of antibodies specific for osteoblastic products. Individual cells and their secretory zones were visualized by light microscopy and counted. Treatment with PTH with or without isoproterenol resulted in increases in the percentages of osteoblastic cells elaborating cAMP, as well as the intensity of immunostaining, but had no effects on MCF-7 cells, a nonosteoblastic breast carcinoma control line. The percentage of cells within each primary osteoblastic cell population isolated or rat osteogenic sarcoma cell clone (G2 or C12) that elaborated bone-specific proteins or that generated cAMP in response to PTH varied with time and the individual cellular preparation, reconfirming the cellular heterogeneity of these systems. This method, in conjunction with techniques such as in vitro hybridization, should prove useful in characterizing discrete osteoblastic bone cell subpopulations and in clarifying mechanisms of hormonal regulation by local and systemic agents.     

Importance of spinal noradrenergic pathways in cardiovascular reflexes and central actions of clonidine and alpha-methyldopa in the rabbit

We have examined in conscious rabbits the chronic effects of 6-hydroxydopamine (6-OHDA)-induced local lesions of the spinal noradrenaline (NA) pathways on (i) resting mean arterial pressure (MAP) and heart rate (HR), (ii) the nasopharyngeal pressor response, (iii) the sympathetic component of the baroreceptor-heart rate reflex (iv) the acute responses to intracisternal (i.c.) clonidine and alpha-methyldopa (alpha-MD), and (v) the acute NA release response produced by i.e. 6-OHDA. One month after injection of 6-OHDA (40 nmol in 4 microliters) into the first cervical spinal cord segment (C1), the NA content was reduced to 29% in C2, 45% in T4 and 61% in L3 with little non-specific damage. Basal MAP was 14% higher (P less than 0.05) than in sham-operated rabbits suggesting increased vasoconstrictor tone. Basal cardiac sympathetic tone was enhanced, but a corresponding increase in cardiac vagal tone resulted in little net effect on resting HR in the spinal NA-depleted group. Spinal NA lesions attenuated the nasopharyngeal pressor reflex by 27% in baroreceptor-intact rabbits and by 38% in sino-aortically denervated (SAD) animals. The lesion did not affect HR range, gain and BP50 of the sympathetic baroreflex. In SAD rabbits, the acute MAP responses to i.c. 6-OHDA (early hypotension, late hypertension) were not affected by spinal NA depletion, but the early fall in HR (cardiac sympathetic inhibition) was abolished. The hypotension produced by i.c. clonidine or alpha-MD was not affected by the lesion, probably because many of the NA terminals in the lower thoracic and upper lumbar cord were still intact. Our results suggest that intraspinal NA fibers have a tonic inhibitory action on spinal preganglionic vasoconstrictor and cardiac motoneurons. The spinal NA neurons affecting vasomotor tone (but not cardiac sympathetic tone) are in turn inhibited by higher vasomotor centers receiving projections from the arterial and trigeminal afferents and thereby participate in vasoconstrictor reflexes.     

Surgical treatment of substernal thyroid disease

The thyroid surgeon must have a full understanding of the anatomy and surgical approaches to the mediastinum. Although most benign substernal goiters may be removed by a transcervical approach, the surgeon needs to know indications for transclavicular and median sternotomy approaches. When there is direct evidence of extension of thyroid cancer into the mediastinum, the possibility of median sternotomy should be considered. This is certainly mandated when disease extends to the inferior mediastinum. Superior mediastinal node dissection is usually easy to approach transcervically. Unilateral extension of the disease may be accessed readily with a transclavicular approach for most cases. Careful dissection of the recurrent laryngeal nerve as well as parathyroids is essential to diminish postoperative morbidity. The morbidity is a reflection of the experience and technical skills of the surgeon as well as the extent of the disease. The best results for resection of substernal thyroid disease are obtained by the experienced thyroid surgeon, not the occasional operator.     

High throughput protein expression screening in the nervous system – needs and limitations

The cellular complexity of the brain (some estimate that there are up to 10³ different cell types) is exceeded by the synaptic complexity, with each of the ∼10¹¹ neurons in the brain having around 10³–10⁴ synapses. Proteomic studies of the synapse have revealed that the postsynaptic density is the most complex multiprotein structure yet identified, with ∼10³ different proteins. Such studies, however, use brain tissue with many different regions and therefore different cell types, and there is clear potential for heterogeneity of protein content at different synapses within and between brain regions. Although large-scale mRNA-based assays are in progress to map this sort of complexity at the cellular level, and indeed all brain-expressed genes, analysis of protein distribution (at synapses and other structures) is still in the very early stages. We review existing large-scale protein expression studies and the specific technical obstacles that need to be overcome before applying the scaling used in nucleic acid based approaches.     

A novel mutation in the last exon of ATRX in a patient with α-thalassemia myelodysplastic syndrome

Abstract:  We describe a patient with acquired alpha-thalassemia myelodysplastic syndrome (ATMDS). A previously healthy 66-year-old man presented with hemoglobin of 9.3 g/dL, mean corpuscular volume 59 fL, and a bone marrow aspirate with increased erythroid precursors and hypolobulated megakaryocytes. Hemoglobin H inclusions were seen in most red cells after 1% brilliant cresyl blue supravital stain of the peripheral blood. At the molecular level, we identified of a novel mutation in the most 3' exon of the ATRX gene ( C GA→ T GA substitution in codon 2407) resulting in a premature termination codon (p.R2407X). This case provides further evidence for a link between ATRX mutations and ATMDS, and suggests a possible role for the conserved Q-box element in ATRX function.