Recovery of vision after treatment of hemodialysis related bilateral optic nerve ischemia.

PURPOSE: We present the case of a patient who lost light perception in both eyes after hemodialysis and subsequently recovered vision after treatment with erythropoietin and intravenous steroids. OBSERVATIONS: Our patient reported loss of light perception in both eyes (NLP) 2 hours after hemodialysis. Examination confirmed NLP vision, chronic retinal vascular changes, and no acute changes in optic nerve appearance. A presumptive diagnosis of posterior optic neuropathy was made. The patient was treated with erythropoietin and intravenous steroids according to the protocol of Nikkah. Over a period of 14 hours, he recovered vision to his baseline. CONCLUSIONS AND IMPORTANCE: Bilateral loss of light perception is a rare complication of hemodialysis. The presumed mechanism is posterior ischemic optic neuropathy. Prompt treatment with erythropoietin and intravenous steroids should be considered in similar situations that result in Posterior ischemic optic neuropathy (PION) related to procedure-based hypotension.

An extremely luminous X-ray outburst at the birth of a supernova.

Massive stars end their short lives in spectacular explosions--supernovae--that synthesize new elements and drive galaxy evolution. Historically, supernovae were discovered mainly through their 'delayed' optical light (some days after the burst of neutrinos that marks the actual event), preventing observations in the first moments following the explosion. As a result, the progenitors of some supernovae and the events leading up to their violent demise remain intensely debated. Here we report the serendipitous discovery of a supernova at the time of the explosion, marked by an extremely luminous X-ray outburst. We attribute the outburst to the 'break-out' of the supernova shock wave from the progenitor star, and show that the inferred rate of such events agrees with that of all core-collapse supernovae. We predict that future wide-field X-ray surveys will catch each year hundreds of supernovae in the act of exploding.

The association of GRB 060218 with a supernova and the evolution of the shock wave.

Although the link between long gamma-ray bursts (GRBs) and supernovae has been established, hitherto there have been no observations of the beginning of a supernova explosion and its intimate link to a GRB. In particular, we do not know how the jet that defines a gamma-ray burst emerges from the star's surface, nor how a GRB progenitor explodes. Here we report observations of the relatively nearby GRB 060218 (ref. 5) and its connection to supernova SN 2006aj (ref. 6). In addition to the classical non-thermal emission, GRB 060218 shows a thermal component in its X-ray spectrum, which cools and shifts into the optical/ultraviolet band as time passes. We interpret these features as arising from the break-out of a shock wave driven by a mildly relativistic shell into the dense wind surrounding the progenitor. We have caught a supernova in the act of exploding, directly observing the shock break-out, which indicates that the GRB progenitor was a Wolf-Rayet star.

Probing microquasars with TeV neutrinos.

The jets associated with galactic microquasars are believed to be ejected by accreting stellar mass black holes or neutron stars. We show that if the energy content of the jets in the transient sources is dominated by electron-proton plasma, then a several hour outburst of 1-100 TeV neutrinos produced by photomeson interactions should precede the radio flares associated with major ejection events. Several neutrinos may be detected during a single outburst by a 1 km(2) detector, thereby providing a powerful probe of microquasar jet physics.

TeV neutrinos from successful and choked gamma-ray bursts.

Core collapse of massive stars resulting in a relativistic fireball jet which breaks through the stellar envelope is a widely discussed scenario for gamma-ray burst production. For very extended or slow rotating stars, the jet may be unable to break through the envelope. Both penetrating and choked jets will produce, by photomeson interactions of accelerated protons, a burst of greater, greater than or similar to 5 TeV neutrinos while propagating in the envelope. The predicted flux, from both penetrating and choked jets, should be easily detectable by planned 1 km(3) neutrino telescopes.

TeV neutrinos and GeV photons from shock breakout in supernovae.

We show that as a Type II supernova shock breaks out of its progenitor star, it becomes collisionless and may accelerate protons to energies >10 TeV. Inelastic nuclear collisions of these protons produce an approximately 1 h long flash of TeV neutrinos and 10 GeV photons, about 10 h after the thermal (10 MeV) neutrino burst from the cooling neutron star. A Galactic supernova in a red supergiant star would produce a photon and neutrino flux of approximately 10(-4) erg cm(-2) s(-1). A km(2) neutrino detector will detect approximately 100 muons, thus allowing to constrain both supernova models and neutrino properties.

Cosmic gamma-ray background from structure formation in the intergalactic medium

The Universe is filled with a diffuse background of gamma-ray radiation, the origin of which remains one of the unsolved puzzles of cosmology. Less than one-quarter of the gamma-ray flux can be attributed to unresolved discrete sources, such as active galactic nuclei; the remainder appears to constitute a truly diffuse background. Here we show that the shock waves induced by gravity in the gas of the intergalactic medium, during the formation of large-scale structures like filaments and sheets of galaxies, produce a population of highly relativistic electrons. These electrons scatter a small fraction of the cosmic microwave background photons in the local Universe up to gamma-ray energies, thereby providing the gamma-ray background. The predicted diffuse flux agrees with the observed background across more than four orders of magnitude in photon energy, and the model predicts that the gamma-ray background, though generated locally, is isotropic to better than five per cent on angular scales larger than a degree. Moreover, the agreement between the predicted and observed background fluxes implies a mean cosmological density of baryons that is consistent with Big Bang nucleosynthesis.

Dexamethasone-facilitated postponement of delivery of an extremely preterm pregnancy complicated by the syndrome of hemolysis, elevated liver enzymes, and low platelets.

OBJECTIVE: Patients with severe preeclampsia and the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome) are at increased risk for perinatal and maternal morbidity, especially in very preterm gestations. When this condition affects a pregnancy on the cusp of viability, a therapeutic intervention to prolong gestation without undue risk to the mother or fetus could be beneficial. METHOD: A single case report and review of the literature. RESULT: We report a patient with HELLP syndrome in whom antenatal administration of high-dose dexamethasone helped achieve disease stabilization and delivery postponement for 9 days of a very preterm fetus estimated to weight less than 600 g. Both mother and infant did well postpartum. CONCLUSION: Administration of antenatal high-dose dexamethasone can be used in carefully selected preterm patients with HELLP syndrome to delay delivery while in utero fetal maturation is accelerated and the maternal condition is optimized. This can be beneficial in carefully selected pregnancies without apparent adverse maternal or perinatal impact.

Single culture media in infectious keratitis.

PURPOSE: To evaluate the usefulness of the various culture media used in the traditional workup in infectious keratitis. METHODS: Microbiology data sheets from all corneal cultures performed at the University of California Davis Medical Center over a 1-year period were reviewed retrospectively. RESULTS: Bacterial cultures were sent in 76 cases. In 19 cases, culture specimens from ulcers were plated onto blood, chocolate, and inhibitory mold agar and were inoculated into an anaerobic medium. In 58 cases, blood and chocolate agar were sent. In 70% of cases, blood and chocolate agar provided identical information. Inhibitory mold agar was positive twice in 39 plates sent. A fungal pathogen had been identified on chocolate agar plates sent for these cases. CONCLUSION: In the evaluation of infectious keratitis, plating onto chocolate agar or blood agar alone is a reasonable alternative to sending multiple cultures.

Environments of the four tryptophans in the extracellular domain of human tissue factor: comparison of results from absorption and fluorescence difference spectra of tryptophan replacement mutants with the crystal structure of the wild-type protein.

The local environments of the four tryptophan residues of the extracellular domain of human tissue factor (sTF) were assessed from difference absorption and fluorescence spectra. The difference spectra were derived by subtracting spectra from single Trp-to-Phe or Trp-to-Tyr replacement mutants from the corresponding spectrum of the wild-type protein. Each of the mutants was capable of enhancing the proteolytic activity of factor VIIa showing that the mutations did not introduce major structural changes, although the mutants were more susceptible to denaturation by guanidinium chloride. The difference spectra indicate that the Trp residues are buried to different extents within the protein matrix. This evaluation was compared with the x-ray crystal structure of sTF. There is excellent agreement between predictions from the difference spectra and the environments of the Trp residues observed in the x-ray crystal structure, demonstrating that difference absorption and particularly fluorescence spectra derived from functional single-Trp replacement mutants can be used to obtain information about the local environments of individual Trp residues in multi-tryptophan proteins.

Sexual dysfunction following treatment for prostate cancer: nursing assessment and interventions.

Treatment modalities for prostate cancer include surgery, radiation therapy, and hormonal manipulation. Sexual dysfunction is a potential sequela of these treatments. Ideally, nursing interventions are begun before treatment is initiated. Pertinent questions enable nurses to elicit specific information needed to develop the patient's care plan. Sexual assessment strategies and interventions, such as the PLISSIT model, that can be implemented when caring for these patients are presented.

The primary self-assembly reaction of bacteriophage lambda cI repressor dimers is to octamer.

Cooperative binding of the bacteriophage lambda cI repressor dimer to specific sites of the phage operators OR and OL controls the developmental state of the phage. It has long been believed that cooperativity is mediated by self-assembly of repressor dimers to form tetramers which can then bind simultaneously to adjacent operator sites. As a first step in defining the individual energy contributions to binding cooperativity, sedimentation equilibrium and steady-state fluorescence anisotropy methods have been used to study the higher order assembly reactions of the free repressor in solution. Wild-type repressor with 5-hydroxytryptophan (5-OHTrp) substituted for the native tryptophan [Ross et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 12023-12027] and two mutant repressor proteins that bind cooperatively to OR but have altered dimerization properties were also studied. We report here that the primary assembly mode of all four proteins is dimer to octamer. It is not dimer to tetramer as previously assumed. While tetramer does form as an assembly intermediate, dimer-octamer assembly is a concerted process so that tetramer is never a predominant species in solution. Sedimentation velocity experiments suggest that the octamer is highly asymmetric, consistent with an elongated shape. This conformation could allow octamers to bind simultaneously to all three operator sites at either OR or OL. Examination of tetramer and octamer concentrations suggests that both species could be involved in cooperative repressor-operator interactions. Our previous work used the unique spectral properties of 5-OHTrp to demonstrate that octamer binds single-operator DNA and is not dissociated to tetramer [Laue et al. (1993) Biochemistry 32, 2469-2472]. Taken together with the results presented here, octamers as well as tetramers must be considered in developing models to explain the cooperativity of lambda cI repressor binding to operator DNA.

Human factor VIIa and its complex with soluble tissue factor: evaluation of asymmetry and conformational dynamics by ultracentrifugation and fluorescence anisotropy decay methods.

Ultracentrifugation and fluorescence anisotropy decay measurements were used to evaluate the asymmetry and conformational dynamics of human blood clotting enzyme VIIa (VIIa) and the complex it forms with a soluble truncation mutant of human tissue factor (sTF) which acts as an essential cofactor for VIIa. Sedimentation velocity experiments showed that both VIIa and the sTF.VIIa complex are highly asymmetric. In each case, the friction ratio f/fsphere, is consistent with a family of general elliposids ranging from prolate to oblate. Fluorescence anisotropy decay experiments were used to limit the family of elliposids which can describe the hydrodynamic behavior of VIIa and sTF.VIIa. For both VIIa and the sTF.VIIa complex, the oblate ellipsoid of revolution was eliminated. In addition, the fluorescence anisotropy decay data clearly show that upon binding sTF.VIIa loses a segmental motion involving a domain containing the active site of the enzyme. This suggests that sTF causes a stabilization of a limited range of VIIa conformations. This stabilization may be important for proper recognition of the TF.VIIa substrate, factor X.

Spectral enhancement of proteins: biological incorporation and fluorescence characterization of 5-hydroxytryptophan in bacteriophage lambda cI repressor.

We have used a tryptophan-requiring Escherichia coli auxotroph to replace the three tryptophan residues of lambda cI repressor with 5-hydroxy-L-tryptophan (5-OHTrp). By using a nonleaky promoter, we have achieved > 95% replacement of tryptophan in the repressor. We show that the absorbance and fluorescence properties of 5-OHTrp-lambda cI are clearly distinct from lambda cI repressor and that the fluorescence of 5-OHTrp-lambda cI repressor can be observed selectively in the presence of exogenous tryptophan. We also show that the 5-OHTrp-lambda cI repressor functional properties, as assessed by measurement of binding constants for self-association and for association to operator DNA, and structural properties, as assessed by fluorescence, are indistinguishable from the native repressor. Based on these results, we anticipate that the availability of spectrally enhanced proteins will significantly enhance the utility of both fluorescence and phosphorescence spectroscopies to study protein structure and function in complex interacting systems.

Tissue factor and its extracellular soluble domain: the relationship between intermolecular association with factor VIIa and enzymatic activity of the complex.

We find that the isolated, extracellular domain of tissue factor (TF1-218; sTF) exhibits only 4% of the activity of wild-type transmembrane TF (TF1-263) in an assay that measures the conversion of factor X to Xa by the TF:VIIa complex. Further, the activity of sTF is manifest only when vesicles consisting of phosphatidylserine and phosphatidylcholine (30/70 w/w) are present. To determine whether the decreased activity results from weakened affinity of sTF for VIIa, we studied their interaction using equilibrium ultracentrifugation, fluorescence anisotropy, and an activity titration. Ultracentrifugation of the sTF:VIIa complex established a stoichiometry of 1:1 and an upper limit of 1 nM for the equilibrium dissociation constant (Kd). This value is in agreement with titrations of dansyl-D-Phe-L-Phe-Arg chloromethyl ketone active site labeled VIIa (DF-VIIa) with sTF using dansyl fluorescence anisotropy as the observable. Pressure dissociation experiments were used to obtain quantitative values for the binding interaction. These experiments indicate that the Kd for the interaction of sTF with DF-VIIa is 0.59 nM (25 degrees C). This value may be compared to a Kd of 7.3 pM obtained by the same method for the interaction of DF-VIIa with TF1-263 reconstituted into phosphatidylcholine vesicles. The molar volume change of association was found to be 63 and 117 mL mol-1 for the interaction of DF-VIIa with sTF and TF1-263, respectively. These binding data show that the sTF:VIIa complex is quantitatively and qualitatively different from the complex formed by TF1-263 and VIIa.