Voyager 2 at neptune: imaging science results.

Voyager 2 images of Neptune reveal a windy planet characterized by bright clouds of methane ice suspended in an exceptionally clear atmosphere above a lower deck of hydrogen sulfide or ammonia ices. Neptune's atmosphere is dominated by a large anticyclonic storm system that has been named the Great Dark Spot (GDS). About the same size as Earth in extent, the GDS bears both many similarities and some differences to the Great Red Spot of Jupiter. Neptune's zonal wind profile is remarkably similar to that of Uranus. Neptune has three major rings at radii of 42,000, 53,000, and 63,000 kilometers. The outer ring contains three higher density arc-like segments that were apparently responsible for most of the ground-based occultation events observed during the current decade. Like the rings of Uranus, the Neptune rings are composed of very dark material; unlike that of Uranus, the Neptune system is very dusty. Six new regular satellites were found, with dark surfaces and radii ranging from 200 to 25 kilometers. All lie inside the orbit of Triton and the inner four are located within the ring system. Triton is seen to be a differentiated body, with a radius of 1350 kilometers and a density of 2.1 grams per cubic centimeter; it exhibits clear evidence of early episodes of surface melting. A now rigid crust of what is probably water ice is overlain with a brilliant coating of nitrogen frost, slightly darkened and reddened with organic polymer material. Streaks of organic polymer suggest seasonal winds strong enough to move particles of micrometer size or larger, once they become airborne. At least two active plumes were seen, carrying dark material 8 kilometers above the surface before being transported downstream by high level winds. The plumes may be driven by solar heating and the subsequent violent vaporization of subsurface nitrogen.

The molecular chaperone sigma 1 receptor mediates rescue of retinal cone photoreceptor cells via modulation of NRF2.

Sigma 1 receptor (Sig1R), a putative molecular chaperone, has emerged as a novel therapeutic target for retinal degenerative disease. Earlier studies showed that activation of Sig1R via the high-affinity ligand (+)-pentazocine ((+)-PTZ) induced profound rescue of cone photoreceptor cells in the rd10 mouse model of retinitis pigmentosa; however the mechanism of rescue is unknown. Improved cone function in (+)-PTZ-treated mice was accompanied by reduced oxidative stress and normalization of levels of NRF2, a transcription factor that activates antioxidant response elements (AREs) of hundreds of cytoprotective genes. Here, we tested the hypothesis that modulation of NRF2 is central to Sig1R-mediated cone rescue. Activation of Sig1R in 661W cone cells using (+)-PTZ induced dose-dependent increases in NRF2-ARE binding activity and NRF2 gene/protein expression, whereas silencing Sig1R significantly decreased NRF2 protein levels and increased oxidative stress, although (+)-PTZ did not disrupt NRF2-KEAP1 binding. In vivo studies were conducted to investigate whether, in the absence of NRF2, activation of Sig1R rescues cones. (+)-PTZ was administered systemically for several weeks to rd10/nrf2+/+ and rd10/nrf2-/- mice. Through post-natal day 42, cone function was significant in rd10/nrf2+/+, but minimal in rd10/nrf2-/- mice as indicated by electroretinographic recordings using natural noise stimuli, optical coherence tomography and retinal histological analyses. Immunodetection of cones was limited in (+)-PTZ-treated rd10/nrf2-/-, though considerable in (+)-PTZ-treated rd10/nrf2+/+mice. The data suggest that Sig1R-mediated cone rescue requires NRF2 and provide evidence for a previously-unrecognized relationship between these proteins.

Role of BDNF/TrkB pathway in the visual system: Therapeutic implications for glaucoma.

INTRODUCTION: Neuroprotective therapeutics are needed to treat glaucoma, an optic neuropathy that results in death of retinal ganglion cells (RGCs). AREAS COVERED: The BDNF/TrkB pathway is important for RGC survival. Temporal and spatial alterations in the BDNF/TrkB pathway occur in development and in response to acute optic nerve injury and to glaucoma. In animal models, BDNF supplementation is successful at slowing RGC death after acute optic nerve injury and in glaucoma, however, the BDNF/TrkB signaling is not the only pathway supporting long term RGC survival. EXPERT COMMENTARY: Much remains to be discovered about the interaction between retrograde, anterograde, and retinal BDNF/TrkB signaling pathways in both neurons and glia. An ideal therapeutic agent for glaucoma likely has several modes of action that target multiple mechanisms of neurodegeneration including the BDNF/TrkB pathway.

Evidence for a retroviral trigger in Graves' disease.

An apparently high frequency of Graves' disease encountered in New Orleans, Louisiana, prompted an investigation for a possible infectious agent that might be triggering the disease in genetically susceptible individuals. We studied 40 patients with Graves' disease, and compared them to the following groups of controls: age and gender matched healthy subjects; patients with multinodular goiter (non-autoimmune thyroid controls); patients with chronic lymphocytic thyroiditis (autoimmune thyroid disease controls) and additional organ or tissue specific autoimmune controls exclusive of thyroid autoimmunity, including patients with Type I diabetes and other endocrine autoimmune complex disorders. Serum antibodies against a prototypic strain of a human intracisternal A-type retroviral particle type 1 (HIAP-1) were detected by a sensitive and specific immunoblotting assay. In 87.5% (35/40) of the Graves' disease patients there was a positive reaction against several HIAP-1-associated proteins, predominantly 97 Kd and 80 Kd, with only 5 showing no reactivity to any. In contrast, 2% (2/105) of sera from normal controls showed positive reactivity. Furthermore, only 10% (1/10) of sera from multinodular goiter control patients and 10% (1/10) of Hashimoto's patients showed reactivity (p < 0.0005). Sera from 3 of 20 (15%) of Type I diabetic patients none of whom had Graves' disease, showed reactivity but there was no reactivity in 9 other patients with one or more of the endocrine autoimmune complex disorders, including Addison's disease, vitiligo, myasthenia gravis and pernicious anemia. In addition we studied two individuals with Graves' disease from each of two families residing outside Louisiana, all of whom were positive for these antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative effectiveness of low-molecular-weight heparins after therapeutic interchange.

Management Case Studies describe approaches to real-life management problems in health systems. Each installment is a brief description of a problem and how it was dealt with. The cases are intended to help readers deal with similar experiences in their own work sites. Problem solving, not hypothesis testing, is emphasized. Successful resolution of the management issue is not a criterion for publication-important lessons can be learned from failures, too.

Health care for the homeless: a public concern.

The number of homeless people in the nation and New Orleans continues to increase. It is an important problem for all citizens but is especially so for the social and medical care agencies. As physicians we are morally bound to help the less fortunate of our communities, and we must also protect the community from the illnesses to which the homeless may be more susceptible. However, because very little is accurately and reliably known about the homeless in New Orleans, little can be efficiently done to aid them. We report the results of our brief surveys to stimulate concern and action in the medical community for these unfortunate people.

Deletion of thioredoxin-interacting protein preserves retinal neuronal function by preventing inflammation and vascular injury.

BACKGROUND AND PURPOSE: Retinal neurodegeneration is an early and critical event in several diseases associated with blindness. Clinically, therapies that target neurodegeneration fail. We aimed to elucidate the multiple roles by which thioredoxin-interacting protein (TXNIP) contributes to initial and sustained retinal neurodegeneration. EXPERIMENTAL APPROACH: Neurotoxicity was induced by intravitreal injection of NMDA into wild-type (WT) and TXNIP-knockout (TKO) mice. The expression of apoptotic and inflammatory markers was assessed by immunohistochemistry, elisa and Western blot. Microvascular degeneration was assessed by periodic acid-Schiff and haematoxylin staining and retinal function by electroretinogram. KEY RESULTS: NMDA induced early (1 day) and significant retinal PARP activation, a threefold increase in TUNEL-positive nuclei and 40% neuronal loss in ganglion cell layer (GCL); and vascular permeability in WT but not TKO mice. NMDA induced glial activation, expression of TNF-α and IL-1ß that co-localized with Müller cells in WT but not TKO mice. In parallel, NMDA triggered the expression of NOD-like receptor protein (NLRP3), activation of caspase-1, and release of IL-1ß and TNF-α in primary WT but not TKO Müller cultures. After 14 days, NMDA induced 1.9-fold microvascular degeneration, 60% neuronal loss in GCL and increased TUNEL-labelled cells in the GCL and inner nuclear layer in WT but not TKO mice. Electroretinogram analysis showed more significant reductions in b-wave amplitudes in WT than in TKO mice. CONCLUSION AND IMPLICATIONS: Targeting TXNIP expression prevented early retinal ganglion cell death, glial activation, retinal inflammation and secondary neuro/microvascular degeneration and preserved retinal function. TXNIP is a promising new therapeutic target for retinal neurodegenerative diseases.

Bilateral episcleritis as a manifestation of cutaneous leukocytoclastic vasculitis.

PURPOSE: The authors describe how bilateral episcleritis can be a sign of active systemic disease and can respond to treatment in a patient with cutaneous leukocytoclastic vasculitis. DESIGN: Case report. METHODS: Comprehensive ophthalmic and physical examination and color photography were used to monitor inflammation and its response to systemic immunosuppression. RESULTS: Systemic cyclophosphamide caused regression of systemic symptoms, cutaneous lesions, and episcleritis. After an 8-month follow-up, the patient has not had a systemic or ocular recurrence. CONCLUSION: Episcleritis may be a manifestation of cutaneous leukocytoclastic vasculitis. Careful examination of ocular inflammation is important in monitoring systemic disease and treatment.

[Production of radiographs of human mandible method and proof of accuracy of the reproducibility of the region]. / Herstellung von Röntgenaufnahmen des menschlichen Unterkiefers-Methode und Nachweis der Genauigkeit der Reproduzierbarkeit des ortes

In continuation of studies by Adolf, Lichtenau, and Epple (1975), the method for preparing congruent radiograms was technically improved. By photometric probing of the radiogram, the reproducibility of a given spot is demonstrated by means of data processing. The results show that in radiograms taken at different times the same spot can be identified.

[Radiodensitometric studies on bone structure following tooth extractions]. / Röntgendensitometrische Knoschestrukturntersuchungen nach Zahnextraktionen

Radiographs of the human mandible, accurately showing the same location, are made at different times after extraction of lateral teeth and examined with regard to changes in the bone structure during wound healing. The radiograms are evaluated by densography and the photometric graphs thus obtained are evaluated by computer. Compared with histological findings known so far, these examinations furnish information on time and location of resorption and production of bone after dental extractions. The first findings are quantitatively presented.

Cytoskeletal changes during neurogenesis in cultures of avain neural crest cells.

Neural crest cells are motile and mitotic, whereas their neuronal derivatives are terminally post-mitotic and consist of stationary cell body from which processes grow. The present study documents changes in the cytoskeleton that occur during neurogenesis in cultures of avain neural crest cells. The undifferentiated neural crest cells contain dense bundles of actin filaments throughout their cytoplasm, and a splayed array of microtubules attached to the centrosome. In newly differentiating neurons, the actin bundles are disrupted and most of the remaining actin filaments are reorganized into a cortical layer underlying the plasma membrane of the cell body and processes. Microtubules are more abundant in newly-differentiating neurons than in the undifferentiated cells, and individual microtubules can be seen dissociated from the centrosome. Neuron-specific beta-III tubulin appears in some crest cells prior to cessation of motility and cell division, and expression increases with total microtubule levels during neurogenesis. To investigate how these early cytoskeletal changes might contribute to alterations in morphology during neurogenesis, we have disrupted the cytoskeleton with pharmacologic agents. Microfilament disruption by cytochalasin immediately arrests the movement of neural crest cells and causes them to round-up, but does not significantly change the morphology of the immature neurons. Microtubule depolymerization by nocodazole slows the movement of undifferentiated cells and causes retraction of processes extended by the immature neurons. These results suggest that changes in the actin and microtubule arrays within neural crest cells govern distinct aspects of their morphogenesis into neurons.

Characterization of truncated and glycosylation-deficient forms of the cation-dependent mannose 6-phosphate receptor expressed in baculovirus-infected insect cells.

A soluble truncated form of the cation-dependent mannose 6-phosphate receptor (CD-MPR) encoding only the extracytoplasmic region, Stop155, and a truncated glycosylation-deficient form of the CD-MPR, Asn81/Stop155, which has been modified to contain only one N-linked glycosylation site at position 81 instead of five, were purified from baculovirus-infected High Five insect cells. The glycosylated recombinant proteins were functional in ligand binding and acid-dependent dissociation as assessed by pentamannosyl phosphate-agarose affinity chromatography. Gel filtration, sucrose gradients, and cross-linking experiments revealed that both Stop155 and Asn81/Stop155 are dimeric, demonstrating that the transmembrane and cytoplasmic region of the receptor as well as N-linked oligosaccharides at positions 31, 57, and 87 are not required for dimerization. The Kd of Stop155 and Asn81/Stop155 for the lysosomal enzyme, beta-glucuronidase, was 0.2 and 0.3 nM, respectively. These values are very similar to those reported for the full-length CD-MPR, demonstrating that the extracellular region of the CD-MPR is sufficient for high-affinity binding and that oligosaccharides at positions 31, 57, and 87 do not influence ligand binding.

Multifaceted approach to medication use policy development: the restriction of meperidine.

As institutions continue to expand their drug policy development efforts in order to improve care and reduce cost, the use of multifaceted approaches offer several benefits. Population data on drug use support the need for policy action. The use of institutional outcomes data in conjunction with published evidence augments the process, and the consensus approach to guideline development engenders medical staff support. Such efforts, however, require significant dedication of human resources. Institutions with limited personnel to allocate to drug policy activities may consider increasing the depth of their efforts (using a multifaceted approach) while limiting the breadth of their efforts (only attempting one or two major targets per year, and doing them well).