Mutarotase in erythrocytes: isolation and properties.

Mutarotase was found in lysed human erythrocytes and in hemoglobin. The enzyme was partially purified by treatment with ethanol and chloroform at -15 degrees C. It was nondialyzable and heat sensitive, and was inhibited by D-galactose, L-arabinose, D-ribose, D-xylose, and D-arabinose.

Yeast killer plasmid mutations affecting toxin secretion and activity and toxin immunity function.

M double-stranded RNA (MdsRNA) plasmid mutants were obtained by mutagenesis and screening of a diploid killer culture partially heat cured of the plasmid, so that a high proportion of the cells could be expected to have only on M plasmid. Mutants with neutral (nonkiller [K-], immune [R+]) or suicide (killer [K+], sensitive [R-] phenotypes were examined. All mutants became K- R- sensitives on heat curing of the MdsRNA plasmid, and showed cytoplasmic inheritance by random spore analysis. In some cases, M plasmid mutations were indicated by altered mobility of the MdsRNA by agarose gel electrophoresis or by altered size of in vitro translation products from denatured dsRNA. Neutral mutants were of two types: nonsecretors of the toxin protein or secretors of an inactive toxin. Of three neutral nonsecretors examined, one (NLP-1), probably a nonsense mutation, made a smaller protoxin precursor in vitro and in vivo, and two made full-size protoxin molecules. The in vivo protoxin of 43,000 molecular weight was unstable in the wild type and kinetically showed a precursor-product relationship to the processed, secreted 11,000-molecular-weight toxin. In one nonsecretor (N1), the protoxin appeared more stable in a pulse-chase experiment, and could be altered in a recognition site required for protein processing.

Inhibition of pyruvate dehydrogenase complex (PDHC) by antipsychotic drugs.

The effects of 11 antipsychotic drugs on the pyruvate dehydrogenase complex (PDHC) prepared from bovine heart and rat brain were investigated. All inhibited PDHC to varying extents. With clinically equivalent doses, chlorpromazine and thioridazine inhibited the most and fluphenazine and thiothixene the least. The relationship of degree of inhibition of PDHC by neuroleptics to clinical improvement of 32 outpatients treated with acetazolamide and thiamine (A + T) ancillary therapy for chronic mental illness suggests that patients treated with psychoactive drugs that inhibit PDHC the least are most likely to have a favorable response with A + T treatment.

Perception and transduction of an elicitor signal in cultured parsley cells.

Treatment of cultured parsley cells or protoplasts with a purified extracellular glycoprotein from Phytophthora megasperma f.sp. glycinea induces the transcription of the same set of defence-related genes as is activated in parsley leaves upon infection. Elicitor activity was shown to reside in a specific portion of the protein moiety which was isolated, sequenced and synthesized. Partial cDNAs encoding the entire mature protein as well as other related proteins have been isolated, indicating the presence of a small gene family. The elicitor-active oligopeptide is located in the C-terminal portion of the deduced amino acid sequence. Binding of the elicitor to target sites on the parsley plasma membrane appears to be the initial event in defence gene activation. The subsequent intracellular transduction of the elicitor signal was shown to involve rapid and transient influxes of Ca2+ and H+, as well as effluxes of K+ and Cl-. Inhibition of elicitor-induced ion fluxes by channel blockers also inhibited phytoalexin synthesis, while stimulation of similar ion fluxes by treatment of cells or protoplasts with the polyene antibiotic, amphotericin B, induced the production of phytoalexins and activated the complete set of defence-related genes in the absence of elicitor.

Influence of disorder on the local density of states in high- T(c) superconducting thin films

Using a low temperature scanning tunneling microscope in the spectroscopic mode, we find that the disorder in a Bi(2)Sr(2)CaCu(2)O(8+delta) thin film modifies dramatically the quasiparticle local density of states. Small, but well-defined superconducting regions, coexisting with dominating semiconducting areas, show well-pronounced gap structures, similar to those observed previously in high-quality single crystals. Surprisingly, between these two regions, the detailed shape of the quasiparticle spectrum is virtually identical to the pseudogap previously observed at temperatures T>T(c), or in the vortex core, at 4.2 K. Thus, the role of the disorder in destroying the superconducting phase is comparable to that of the magnetic field or thermal fluctuations.

Acetazolamide and thiamine: an ancillary therapy for chronic mental illness.

Twenty-four chronic schizophrenic patients were treated successfully with the addition of acetazolamide and thiamine (A + T) to their unchanged existing therapies in a double-blind, placebo-controlled crossover study. Therapeutic effects were measured by the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. Overall, 50% of the patients showed improvement on all assessment scales. No untoward effects occurred in these patients or in patients in previous studies who have been treated continuously with A + T therapy for as long as 3 years.

Study design in the evaluation of breast cancer imaging technologies.

RATIONALE AND OBJECTIVES: Bringing a new imaging technology to market is a complex process. Beyond conceptualization and proof of concept, obtaining U.S. Food and Drug Administration (FDA) approval for clinical use depends on the documented experimental establishment of safety and efficacy. In turn, safety and efficacy are evaluated in the context of the intended use of the technology. The purpose of this study was to examine a conceptual framework for technology development and evaluation, focusing on new breast imaging technologies as a highly visible and current case in point. MATERIALS AND METHODS: The FDA views technology development in terms of a preclinical and four clinical phases of assessment. With a concept of research and development as a learning model, this phased-assessment concept of regulatory review against intended use was integrated with a five-level version of a hierarchy-of-efficacy framework for evaluating imaging technologies. Study design and analysis issues are presented in this context, as are approaches to supporting expanded clinical indications and new intended uses after a new technology is marketed. CONCLUSION: Breast imaging technologies may be intended for use as replacements for standard-of-care technologies, as adjuncts, or as complementary technologies. Study designs must be appropriate to establish claims of superiority or equivalence to the standard for the intended use. Screening technologies are ultimately judged on their demonstrated effectiveness in decreasing cause-specific mortality through early detection, but they may be brought to market for other uses on the basis of lesser standards of efficacy (eg, sensitivity, specificity, positive and negative predictive value, and stage of disease detected).

Disorder effects in pnictides: a tunneling spectroscopy study.

We present the synthesis and the tunneling spectroscopy study of superconducting FeSe(0.5)Te(0.5) (T(c) = 14 K), SmFeAsO(0.85) (T(c) = 54 K) and SmFeAsO(0.9)F(0.1) (T(c) = 45 K). The samples were characterized by Rietveld refinement of x-ray diffraction patterns and transport as well as temperature-dependent magnetic measurements. Tunneling experiments on FeSe(0.5)Te(0.5) revealed a single superconducting gap ∼ 1 meV in BCS-like tunneling conductance spectra. In SmFeAsO(0.85) and SmFeAsO(0.9)F(0.1), however, more complex spectra were observed, characterized by two gap-like structures at ∼ 4 and ∼ 10 meV. These spectra are qualitatively understood assuming a two-band superconductor with a 's ±' order parameter. We show that, depending on the sign relation between the pairing amplitudes in the two bands, the interband quasiparticle scattering has a crucial effect on the shape of the tunneling spectra. On the other hand, single-gap spectra found in FeSe(0.5)Te(0.5) are more compatible with a disorder-induced 's '-wave gap, due to the Se-Te substitution.

Probing the superfluid velocity with a superconducting tip: the Doppler shift effect.

We address the question of probing the supercurrents in superconducting (SC) samples on a local scale by performing scanning tunneling spectroscopy (STS) experiments with a SC tip. In this configuration, we show that the tunneling conductance is highly sensitive to the Doppler shift term in the SC quasiparticle (QP) spectrum of the sample, thus allowing the local study of the superfluid velocity. Intrinsic screening currents, such as those surrounding the vortex cores in a type II SC in a magnetic field, are directly probed. With Nb tips, the STS mapping of the vortices, in single crystal 2H-NbSe(2), reveals both the vortex cores, on the scale of the SC coherence length xi, and the supercurrents, on the scale of the London penetration length lambda. A subtle interplay between the SC pair potential and the supercurrents at the vortex edge is observed. Our results open interesting prospects for the study of screening currents in any superconductor.

Scanning tunneling spectroscopy on the novel superconductor CaC6.

We present scanning tunneling microscopy and spectroscopy of the newly discovered superconductor CaC6. The tunneling conductance spectra, measured between 3 and 15 K, show a clear superconducting gap in the quasiparticle density of states. The gap function extracted from the spectra is in good agreement with the conventional BCS theory with Delta0=1.6+/-0.2 meV. The possibility of gap anisotropy and two-gap superconductivity is also discussed. In a magnetic field, direct imaging of the vortices allows us to deduce a coherence length in the ab plane xiab approximately 33 nm.

The use of an isopyrine-phenylbutazone compound in migraine.

A randomized double-blind study of 40 patients with migraine attacks was carried out to compare an intravenous injection of isopyrine 240 mg plus phenylbutazone 130 mg (Tomanol; Byk-Gulden) with a placebo. Isopyrine is an analgesic with a central sedative action which potentiates the action of phenylbutazone, an inhibitor of prostaglandin biosynthesis and circulation. In 15 patients who received the drug the migraine attack was terminated within 5 minutes of administration, apart from a mild residual headache in 2 cases. No recurrence was reported after 24 hours. The placebo administered to 25 patients gave total relief in 3, a slight improvement of symptoms in 12 and had no effect in 10. Treatment with isopyrine-phenylbutazone compound was based on the immediate central analgesic and sedative action of isopyrine, and the inhibition of the vaso-active action of prostaglandins by phenylbutazone.

Deletion mutants in the gene encoding the herpes simplex virus type 1 immediate-early protein ICP0 exhibit impaired growth in cell culture.

We report the construction and characterization of deletion mutants in the herpes simplex virus type 1 gene encoding the immediate-early protein ICP0. In the event that ICP0 proved to play an essential role in virus replication, ICP0-transformed Vero cells were generated to serve as permissive hosts for such mutants. Two mutants, dlX0.7 and dlX3.1, were isolated in these cells by a marker rescue-transfer procedure involving the rescue of an ICP4 deletion mutant and the simultaneous insertion of a linked deletion in the ICP0 gene. Mutant dlX0.7 contained a 700-base-pair deletion in both copies of ICP0. The deletion lay entirely within the transcript specified by the gene. dlX0.7 induced the synthesis of an ICP0-specific mRNA that was approximately 0.7 kilobases smaller than the corresponding mRNA specified by wild-type virus. The 3.1-kilobase deletion in both copies of the ICP0 gene in mutant dlX3.1 removed the majority of the transcriptional-regulatory signals and coding sequences, retaining only sequences at the 3' end of the gene. As expected, no ICP0-specific mRNA was detected in dlX3.1-infected Nero cells (G418-resistant Vero cells). Both mutants grew in all cells tested, although their burst sizes were 10- to 100-fold lower than that of wild-type virus. Although the plaque sizes of dlX0.7 and dlX3.1 were equally small on Nero and ICP0-transformed cells, the plating efficiency of the mutants was 15- to 50-fold greater on ICP0-transformed cells than on Nero cells. The mutants exhibited modest interference with the growth of wild-type virus in mixed infections, an effect that was abolished by UV irradiation of the mutants, implying that interference required viral gene expression. Polypeptide profiles generated by the mutants in Nero cells were qualitatively similar to that of wild-type virus. Quantitatively, only slight reductions in the levels of certain late viral polypeptides were observed, a phenomenon also borne out by analysis of viral glycoproteins. Both mutants induced the synthesis of significant, although reduced, levels of viral DNA relative to wild-type virus. Taken together, the results demonstrate that ICP0 is not essential for productive infection in cell culture but that this protein plays a significant role in viral growth, as indicated by the impaired abilities of the mutants to replicate.

A comparison of the cerebral uptake and metabolism of labeled glucose and deoxyglucose in vivo in rats.

Experimental evidence indicated that: 1) [14C]deoxyglucose-6-phosphate (14C-DG-6-P) in brain (and other rat tissues) did not increase with time after injection of 14C-DG, 2) 14C-DG-6-P in rat brain (and other tissues) did not correlate with glucose metabolism, 3) 14C-DG-6-P in rat brain (and other tissues) had a significant negative correlation with glucose-6-phosphatase activity. Further, arterio-venous studies in rats, in which the cerebral uptake and metabolism of labeled glucose were compared directly with those of labeled DG (and labeled fluorodeoxyglucose, FDG), employing double labeled techniques, showed that DG (and FDG) cannot be used to measure glucose uptake and/or metabolism.