Suppression of streptozotocin-induced type-1 diabetes in mice by radon inhalation.

We examined the protective effect of radon inhalation on streptozotocin (STZ)-induced type-1 diabetes in mice. Mice inhaled radon at concentrations of 1000, 2500, and 5500 Bq/m3 for 24 hours before STZ administration. STZ administration induced characteristics of type-1 diabetes such as hyperglycemia and hypoinsulinemia; however, radon inhalation at doses of 1000 and 5500 Bq/m3 significantly suppressed the elevation of blood glucose in diabetic mice. Serum insulin was significantly higher in mice pre-treated with radon at a dose of 1000 Bq/m3 than in mice treated with a sham. In addition, superoxide dismutase activities and total glutathione contents were significantly higher and lipid peroxide was significantly lower in mice pre-treated with radon at doses of 1000 and 5500 Bq/m3 than in mice treated with a sham. These results were consistent with the result that radon inhalation at 1000 and 5500 Bq/m3 suppressed hyperglycemia. These findings suggested that radon inhalation suppressed STZ-induced type-1 diabetes through the enhancement of antioxidative functions in the pancreas.

Mechanism of superconductivity in the polyhedral-network compound Ba8Si46.

The silicon clathrates--materials composed of metal-doped Si(20) dodecahedra--were identified as the first superconductors based on pure silicon networks. The mechanism of superconductivity in these materials can be obtained by studying their phonon modes, as modified by isotope substitution, and specific-heat measurements. Here, we present experimental studies that provide strong evidence that superconductivity in Ba(8)Si(46) is explained in the framework of phonon-mediated Bardeen-Cooper-Schriefer theory. Analyses using the McMillan approximation of the Eliashberg equation indicate that the superconducting mechanism is in the medium coupling regime, but at the high-end limit. The large density of states at the Fermi level, which arises from hybridization of the Si(20) cluster and Ba orbitals, is responsible for the unexpectedly high superconducting temperature. The temperature evolution of the specific heat unambiguously shows that this is an s-wave symmetry superconductor.

Effects of elbow flexion on radial nerve motor conduction velocity.

The position of the elbow while conducting motor studies of the radial nerve is generally extended (15) or slightly flexed (10), but little is known about the effects of elbow flexion on the radial motor conduction velocity. We attempted to measure the effects of the elbow position on the radial motor conduction velocity, as well as directly measure the change in the length of the nerve at different elbow positions in the cadaver. In addition, we established normal values for the radial F-wave with the recording electrode on the extensor indicis proprius muscle. Radial motor nerve conduction was studied in 25 normal subjects to evaluate the effect of 3 different elbow positions (0 degree, 45 degrees, and 90 degrees) on motor conduction velocity (MCV) across the elbow. Direct (in situ) radial nerve measurements were performed on four cadaver specimens to compare changes in nerve length during elbow flexion. Normal values for radial F-wave latencies recording from the extensor indicis proprius muscle were also determined in 23 subjects. The radial MCV decreased significantly as the elbow flexed from 0 degree to 90 degrees. The normal range of values for radial motor nerve conduction at 0 degree of elbow flexion was 71.7 +/- 4.7 m/s, 68.9 +/- 4.9 at 45 degrees of elbow flexion, and 62.0 +/- 6.4 m/s at 90 degrees elbow flexion. Actual (in situ) radial nerve measurements were also found to decrease in length as the elbow flexed. The minimal radial F-wave latency was 19.8 +/- 3.7 milliseconds. For routine determination of motor nerve conduction velocity across the elbow, we recommend that the elbow be fully extended, as the distance measurement most accurately reflects the maximum anatomic length of the nerve. We also feel that the radial nerve F-wave latency is readily obtainable from the extensor indicis proprius muscle.

Supramolecular complex of cytochrome c with lariat ether: solubilization, redox behavior and catalytic activity of cytochrome c in methanol.

A variety of lariat ethers were employed to solubilize water-soluble cytochrome c in methanol, in which alcohol, ether, ester, amine, and amide functionalities were attached as cation-ligating side arms to 18-crown-6, 15-crown-5, and 12-crown-4 rings. Among these lariat ethers, the alcohol-armed 18-crown-6 derivative offered the highest solubilization efficiency for cytochrome c via supramolecular complexation. The resulting cytochrome c-lariat ether complexes were electrochemically and spectroscopically characterized and confirmed to have redox-active heme structures of 6-coordinate low-spin population in methanol. Some of them catalyzed the oxidation of pinacyanol chloride with hydrogen peroxide in methanol and exhibited higher activities than unmodified cytochrome c and its poly(ethylene glycolated) derivative. Since the supramolecular complexation between lariat ether and cytochrome c includes extremely simple procedures, it provides a facile preparation method of effective biocatalysts working in organic solvents from metalloproteins.

The prevalence of lumbar paraspinal spontaneous activity in asymptomatic subjects.

Electrodiagnostic findings of fibrillations and positive sharp waves in the lumbosacral paraspinals in patients without previous back surgery has been generally considered to be abnormal, consistent with posterior rami denervation. In some cases, it is the only abnormality on the electromyographic examination. This study was undertaken to determine the prevalence of abnormal spontaneous activity in lumbosacral paraspinals in asymptomatic individuals. Nine (14.5%) of 62 subjects studied had positive sharp waves or fibrillations noted on the needle examination of bilateral lumbosacral paraspinal muscles. There was a significant increase in the prevalence of abnormal activity with increasing age. This suggests that caution should be taken in attributing radiculopathy as the etiology of low back pain when electromyographic lumbosacral paraspinal abnormalities are the only positive findings in the middle-aged or older individual.

Ultraviolet resonance Raman and absorption difference spectroscopy of myoglobins: titration behavior of individual tyrosine residues.

The UV resonance Raman spectra of horse and sperm whale myoglobin excited at 240 nm show bands between 600 and 1700 cm-1 which derive from tyrosyl and tryptophyl residues. No significant contribution from phenylalanine and peptide backbone vibrations occurs at this excitation wavelength. We examine the pH dependence of the UV resonance Raman and UV absorption difference spectra of these myoglobins to correlate the local protein environment of the tyrosyl residues as given by the protein crystal structure to their pKa values, molar absorptivities, and Raman cross sections. Some of our pKa values for the tyrosinate residues of horse Mb differ from those of previous studies. We show that the lambda max values, the molar absorptivities, and the Raman cross sections are sensitive to the local environment of the tyrosinate residues in the protein. We relate differences in the tyrosyl absorption spectra to differences in Raman cross sections. In addition, we discuss the importance to the Raman cross sections of the local electromagnetic field enhancement due to the dielectric environment of the tyrosinate residues in the protein. This local field should scale the Raman cross sections in a way useful as a probe of the average aromatic amino acid residue environment.

Resonance Raman study on cytochrome c peroxidase and its intermediate. Presence of the Fe(IV) = O bond in compound ES and heme-linked ionization.

Resonance Raman spectra of ferrous and ferric cytochrome c peroxidase and Compound ES and their pH dependences were investigated in resonance with Soret band. The Fe(IV) = O stretching Raman line of Compound ES was assigned to a broad band around 767 cm-1, which was shifted to 727 cm-1 upon 18O substitution. The 18O-isotopic frequency shift was recognized for Compound ES derived in H218O, but not in H216O. This clearly indicated occurrence of an oxygen exchange between the Fe(IV) = O heme and bulk water. The Fe(IV) = O stretching Raman band was definitely more intense and of higher frequency in D2O than in H2O as in Compound II of horseradish peroxidase, but in contrast with this its frequency was unaltered between pH 4 and 11. The Fe(II)-histidine stretching Raman line was assigned on the basis of the frequency shift observed for 54Fe isotopic substitution. From the intensity analysis of this band, the pKa of the heme-linked ionization of ferrocytochrome c peroxidase was determined to be 7.3. The Raman spectrum of ferricytochrome c peroxidase strongly suggested that the heme is placed under an equilibrium between the 5- and 6-coordinate high-spin structures. At neutral pH it is biased to the 5-coordinate structure, but at the acidic side of the transition of pKa = 5.5 the 6-coordinate heme becomes dominant. F- was bound to the heme iron at pH 6, but Cl- was bound only at acidic pH. Acidification by HNO3, H2SO4, CH3COOH, HBr, or HI resulted in somewhat different populations of the 5- and 6-coordinate forms when they were compared at pH 4.3. Accordingly, it is inferred that a water molecule which is suggested to occupy the sixth coordination position of the heme iron is not coordinated to the heme iron at pH 6 but that protonation of the pKa = 5.5 residue induces an appreciable structural change, allowing the coordination of the water molecule to the heme iron.

Distinct heme-substrate interactions of lactoperoxidase probed by resonance Raman spectroscopy: difference between animal and plant peroxidases.

Resonance Raman scattering from cow milk lactoperoxidase (LPO) and its complexes with various electron donors and inhibitors was investigated. The Raman spectrum of LPO is strikingly close to that of hog intestinal peroxidase but distinctly dissimilar to that of horseradish peroxidase (HRP). The v10 frequency suggested the six-coordinate high-spin structure of heme for native LPO in contrast with the five-coordinate high-spin structure for HRP. For the v10 band, benzohydroxamic acid caused a frequency shift with HRP but not with LPO. Guaiacol, o-toluidine, and histidine brought about a frequency shift of the v4 mode for LPO but not for HRP. The frequency shift was restored upon removal of the substrate or inhibitor by dialysis. The down shift of the v4 frequency is considered to represent an appreciable donation of electrons from the substrate or inhibitor to the porphyrin LUMO and thus their direct interaction with the heme group. From the relative intensity of the shifted and unshifted v4 lines, the dissociation constant was determined to be Kd = 52 mM for guaiacol and Kd = 87 mM for histidine at pH 7.4. The binding of histidine was relatively retarded in the presence of sulfate anion (Kd = 150 mM for 0.53 M sulfate present), and imidazole alone yielded no frequency shift, indicating the binding of the carboxyl group of histidine to the protein cationic site on one hand and a weak charge-transfer interaction between the imidazole group and the heme group on the other.

The role of heparin in the changes of lipid patterns during a single hemodialysis.

The effects of heparin administered during dialysis on serum lipids and lipoproteins were evaluated by comparing dialysis with heparin and dialysis without heparin. Gabexate mesilate (GM), a synthetic proteinase inhibitor, was used as an anticoagulant during dialysis without heparin. In dialysis with heparin, significant increases were observed in free fatty acids (FFA), high-density lipoprotein cholesterol (HDL-C), and plasma lipolytic activity (PLA). Triglyceride (TG) was decreased reciprocally and the lipoprotein electrophoretic pattern was markedly modified. In contrast, in dialysis without heparin, no significant changes were observed in all parameters of lipid metabolism. These data suggest that dialysis induced changes in lipids are mainly caused by heparin and that acetate and glucose in dialyzate make an almost negligible contribution to abnormal lipid patterns in patients on maintenance hemodialysis.

The effect of heparin-free dialysis on abnormal lipid metabolism in patients on regular dialysis treatment.

To elucidate the contributory role of heparin to abnormal lipid metabolism in patients on regular haemodialysis (RDT), six week haemodialysis without heparin was performed using gabexate mesilate in combination with low dose aspirin. Total cholesterol and beta-lipoprotein were significantly increased at the fourth week after the start of the study. No significant changes were observed in high density lipoprotein cholesterol, phospholipid, triglyceride, lipoprotein phenotype and post heparin lipolytic activity. Routine dose heparin in RDT might have a favourable effect on abnormal lipid metabolism by inducing post heparin lipolytic activity in circulating blood, not by reducing the lipid removing activity in peripheral tissues.

The pH dependence of the resonance raman spectra and structural alterations at heme moieties of various c-type cytochromes.

The pH dependence of resonance Raman spectra were studied for ferrous and ferric cytochromes c, c2, c3, c-551, and c-555. The frequencies of the 1565 cm-1 (ferric) and 1539 cm-1 lines (ferrous) were sensitive to the replacement of the sixth ligand. The titration curve for the 1565 cm-1 line of cytochrome c was parallel with that for the 695 nm band. The pH dependence of the 1539 cm-1 line of ferrous cytochrome c3 suggested the stepwise replacement of the sixth ligand of its four hemes, although such pH dependence was not recognized for the Raman spectra of other ferrous cytochromes investigated. The relative intensities of three Raman lines at 1639, 1587, and 1561 cm-1 of ferric protoporphyrin bis-imidazole complex were changed clearly by the presence of detergents. The relative intensities of the corresponding three Raman lines of cytochromes b5 and c were close to those of the ferric porphyrin complex in the presence and absence of detergents, respectively, suggesting an appreciable difference in their heme environments. Reduced hemin in detergent solution, unexpectedly, gave the Raman spectrum of ferric low spin type.