Pressure dependence of the superconducting transition temperature of magnesium diboride.

We studied the pressure and temperature dependence of the electrical resistivity of the superconducting compound magnesium diboride (MgB(2)). The superconducting transition temperature decreases monotonically with pressure, being parabolic or linear, depending on samples. The rate of decrease under pressure is higher than in conventional superconductors. We discuss our results in terms of the semimetallic character of the electronic band structure of MgB(2).

Characterization of 5-oxo-L-prolinase in normal and tumor tissues of humans and rats: a potential new target for biochemical modulation of glutathione.

5-Oxo-L-prolinase (5-OPase) is an enzyme of the gamma-glutamyl cycle involved in the synthesis and metabolism of glutathione (GSH), which is known to protect cells from the cytotoxic effects of chemotherapy and radiation. Previous studies on rats have shown that administration of the cysteine prodrug L-2-oxothiazolidine-4-carboxylate, a 5-oxo-L-proline analogue that is metabolized by 5-OPase, preferentially increases the GSH content of normal tissues while paradoxically decreasing it in the tumor and results in an enhanced in vivo tumor response to the anticancer drug melphalan. These observations initiated the present study of 5-OPase in experimental models and clinical specimens to investigate the potential role of this enzyme in the selective modulation of GSH in normal and tumor tissues. First, 5-OPase activity was measured in tissues of tumor-bearing rats, in the peripheral mononuclear cells of normal human subjects, and in surgically resected tumor and the adjacent normal tissues from patients. We found that the activity of 5-OPase in human kidney, liver, and lung is significantly lower than that found in rats. Second, we have raised a polyclonal IgG anti-5-OPase antibody by immunizing rabbits with purified 5-OPase from rat kidney. This antibody has very high affinity (shown by immunoprecipitation) and specificity (shown by Western blot) and cross-reacts with human 5-OPase (shown by Western blot and immunohistochemistry). It was then used to examine the distribution of 5-OPase in paired normal and neoplastic human specimens using Western blot and immunohistochemistry. Examination of paired normal and neoplastic tissues of stomach and lung revealed a significantly lower level of 5-OPase in tumor tissues than in the paired normal tissues. In colon tissues, there is no significant difference in 5-OPase level between the normal and tumor tissues. These findings could have implications for both carcinogenesis and therapy.

Coordinate estrogen induction of vitellogenin and a small serum protein mRNA in Xenopus laevis liver.

We have used plus-minus hybridization to identify Xenopus liver cDNA clones of mRNAs whose levels are regulated by estrogen. One clone identified in this way was shown to be a nearly full-length cDNA clone of the mRNA coding for a small 22 000 dalton estrogen-inducible serum protein (EISP). Quantitation of EISP mRNA levels by in vitro translation and by hybridization to the cloned DNA demonstrated a 7-12-fold estrogen induction of EISP mRNA, both in vivo and in primary Xenopus liver cultures. The kinetics of induction of EISP mRNA closely parallel those of the mRNA coding for the abundant estrogen-inducible serum protein, vitellogenin. In contrast, the massive, and toxic, estrogen-mediated accumulation of vitellogenin in serum of male Xenopus laevis is accompanied by a sharp decline in the levels of albumin mRNA and in the levels of the mRNAs coding for several other serum proteins.

Pulmonary oxygen toxicity in mice is characterized by alterations in ascorbate redox status.

Pulmonary oxygen toxicity results from disruption of the usual antioxidant defenses of the body. We therefore investigated whether mice that suffer from oxygen toxicity show significant alterations in the redox status of ascorbate, an important antioxidant, as reflected by changes in the relative amounts of its oxidized and reduced forms. Mice were exposed to air or hyperoxia (> 97% O2, 760 mmHg). After 5 days, plasma and saline-perfused lungs were removed and levels of ascorbate (AA), oxidized ascorbate [dehydroascorbate (DHAA)], and total ascorbate species ([AA+DHAA]) were determined by a sensitive and specific high-performance liquid chromatography assay; lungs were also assayed for total glutathione and glutathione disulfide (GSSG), an established marker of oxidative stress. We found that with hyperoxic exposure plasma AA increased by 32%, plasma DHAA increased substantially from previously undetectable levels, and the DHAA-to-[AA+DHAA] ratio increased. In contrast, in lung, [AA+DHAA] decreased by 41%. Plasma AA, DHAA, and [AA+DHAA] each correlated inversely with lung [AA+DHAA] and directly with lung GSSC. We conclude that alterations in plasma ascorbate redox status reflect pulmonary oxygen toxicity in mice. Our results suggest that further investigations are warranted to determine whether similar findings occur in humans and have clinical utility.

Selective deintercalation of apex over face-shared oxide ions in the topotactic reduction of Sr7Mn4O15 to Sr7Mn4O12.

Sodium hydride selectively deintercalates the apex rather than face-shared oxide ions within the structure of Sr(7)Mn(4)O(15) leading to the formation of the structurally related reduced phase Sr(7)Mn(4)O(12).

Atomic-scale structure of biogenic materials by total X-ray diffraction: a study of bacterial and fungal MnOx.

Biogenic materials are produced by microorganisms and are typically found in a nanophase state. As such, they are difficult to characterize structurally. In this report, we demonstrate how high-energy X-ray diffraction and atomic pair distribution function analysis can be used to determine the atomic-scale structures of MnO(x) produced by bacteria and fungi. These structures are well-defined, periodic, and species-specific, built of Mn-O(6) octahedra forming birnessite-type layers and todorokite-type tunnels, respectively. The inherent structural diversity of biogenic material may offer opportunities for practical applications.

Phosphoglucomutase-1 (PGM1) W23 and W26 variants detected in the Taiwanese Chinese population.

Phosphoglucomutase-1 (PGM1) phenotyping among Taiwanese Chinese was carried out on thin layer agarose gel using isoelectric focusing techniques. During routine paternity testing, two new PGM1 variants not previously observed in Taiwanese Chinese were detected. These are PGM1 W23 and PGM1 W26.

Transcultural factors in child abuse.

A transcultural analysis of 54 cases of child abuse that were consecutively referred to the psychiatric clinic of the Red Cross War Memorial Children's Hospital is presented. Among the data studied were the legal status of the abused child, the nature of the injuries received and the characteristics of the abusers. It is stressed that this was a pilot investigation, and that there is a need for better reporting and further research.

Induction of estrogen receptor and reversal of the nuclear/cytoplasmic receptor ratio during vitellogenin synthesis and withdrawal in Xenopus laevis.

The levels of cytoplasmic and nuclear estrogen receptor have been determined in livers of male Xenopus laevis stimulated by estradiol-17 beta to synthesize vitellogenin mRNA. Estrogen receptor levels were also determined in unstimulated liver and following long term withdrawal of estrogen. In unstimulated liver cells, which do not contain detectable vitellogenin mRNA, more than 80% of the estrogen receptor is located in the nucleus (550 high affinity estrogen binding sites/nucleus), while the cytoplasm contains only 100 high affinity estrogen binding sites/cell. Administration of estradiol-17 beta, which induces massive synthesis and accumulation of vitellogenin mRNA, induces the estrogen receptor as well. The nuclear receptor level rises to approximately 2,000 estrogen binding sites/cell, while the cytosol receptor increases to only 150 sites/cel. Liver cells of male X. laevis which have been withdrawn from estrogen for 70 days exhibit a striking change in receptor levels. The nuclear receptor returns to the level prevailing in unstimulated cells (approximately 500 sites/cell) while the cytosol receptor level rises to more than 1,200 sites/cell (equivalent to 260 fmol/g of tissue). The existence of a pool of cytosol receptor, which is rapidly available for induction of vitellogenin mRNA, may in part explain the shorter lag period and more rapid induction of vitellogenin mRNA observed during secondary estrogen stimulation of withdrawn Xenopus liver cells.

Activation of vitellogenin gene transcription is a direct response to estrogen in Xenopus laevis liver.

Estrogen induces the synthesis of vitellogenin mRNA by activating transcription of the vitellogenin genes. Quantitative inhibition of liver protein synthesis by cycloheximide does not prevent activation of vitellogenin gene transcription. The relative transcription rate of the vitellogenin genes in estrogen stimulated liver is similar in control and cycloheximide treated animals (800-1000 ppm). Selective estrogen activation of vitellogenin gene transcription therefore represents a direct effect of estrogen on vitellogenin gene transcription which can occur without any change in the cells' protein complement. Two other cellular responses to estrogen, the induction of nuclear estrogen receptor, and an increased rate of total nuclear RNA synthesis, are blocked by cycloheximide administration. Since the overall rate of vitellogenin mRNA synthesis is a function of both the selective estrogen activation of vitellogenin gene transcription which is not blocked by cycloheximide and the increased rate of total nuclear RNA synthesis which is blocked by cycloheximide, the total rate of vitellogenin mRNA synthesis is markedly reduced following cycloheximide administration.

Phosphoglucomutase-1 polymorphism among Chinese in Taiwan.

Phosphoglucomutase-1 (PGM1) phenotyping of 1,128 Chinese blood donors was performed by thin-layer isoelectric focusing on agarose. The PGM1 gene frequencies were: 1A, 0.6005; 1B, 0.1500; 2A, 0.1510; 2B, 0.0973, and rare variants, 0.0058. The rare variants found in this series were PGM1 W21, W2, W3, W6 and W9 (or W10) with PGM1 W21 being the most common variant among Chinese with a phenotype frequency of 0.8%.

Phosphoglucomutase phenotyping among Chinese in Taiwan.

Phosphoglucomutase 1 (PGM1) phenotyping was performed in 1,128 Chinese blood donors by thin-layer isoelectric focusing on agarose. The PGM1 gene frequencies were as follows: 1A, 0.6005; 1B, 0.1500; 2A, 0.1510, 2B, 0.0973; variants, 0.0058, with W21, 0.0040. The variants found in this series were PGM1 W21, W2, W3, W6 and W9 (or W10) with PGM1 W21 being the most common variant among Chinese, having a phenotype frequency of 0.8%.

The role of estrogen receptor in Xenopus laevis vitellogenin gene expression.

Administration of estradiol 17 beta [estra-1,3,5(10)-triene-3,17-beta-diol] to male Xenopus laevis induces the massive synthesis by the liver of the egg yolk precursor phospholipoglycoprotein, vitellogenin, and its cognate mRNAs. Restimulation of male X. laevis that have been previously induced to synthesize vitellogenin mRNA but are inactive in vitellogenin mRNA synthesis at the time of restimulation with estrogen results in more rapid accumulation of vitellogenin mRNA and more efficient transcription of the vitellogenin genes than occurs following primary estrogen stimulation. The estrogen receptor system that mediates estrogen action in this organism exhibits several unusual properties. The cytoplasm of unstimulated liver cells contains high levels of a middle-affinity estrogen-specific binding protein and little if any estrogen receptor. The properties of the estrogen binding protein are consistent with a role in protecting estradiol 17 beta against metabolism, as a fraction of cytoplasmic estradiol 17 beta is not subject to rapid metabolism. In addition, similar binding activities are found in all Xenopus tissues surveyed that respond to steroid hormones. The induction of nuclear estrogen receptor is coincident with the onset of vitellogenin mRNA accumulation. However, an increased level of estrogen receptor is not responsible for the elevated rate of vitellogenin gene transcription observed following restimulation with estrogen.

The effect of conjugated equine estrogens on ovariectomy-induced osteopenia in the rat.

The effect of estrogen replacement on ovariectomy-induced bone loss was evaluated in mature Sprague-Dawley rats. Undecalcified tibia of ovariectomized rats were processed for quantitative histologic assessment of cancellous bone in longitudinal sections from the primary and secondary spongiosa of the proximal metaphysis. Bone content in tissue specimens was quantified as the parameter B. Ar, two-dimensional bone mineral area. Estrogen, supplied as orally administered conjugated equine estrogens, prevented bone loss through 6 weeks of treatment. The effect of conjugated equine estrogens was dose-dependent, with significant protection against bone loss observed at doses of 10 micrograms/kg/day and higher.

Nuclease sensitivity and DNA methylation in estrogen regulation of Xenopus laevis vitellogenin gene expression.

Estrogen activates transcription of the vitellogenin genes in livers of male Xenopus laevis. We have examined the conformation of the vitellogenin genes in chromatin and the methylation state of one vitellogenin gene during the process of estrogen stimulation and withdrawal. Sensitivity of the vitellogenin genes to DNase I digestion parallels transcription. The vitellogenin genes are insensitive to DNase I digestion in unstimulated liver cells, become more sensitive to DNase I digestion following estrogen activation of vitellogenin gene transcription, and are insensitive to DNase I digestion in liver cells withdrawn from estrogen. In contrast, the methylation state of nine potential methylation sites within the vitellogenin A1 gene is identical in red blood cells, unstimulated and withdrawn liver, estrogen-stimulated liver, and hepatocytes purified from estrogen-stimulated liver. Rapid transcription of the vitellogenin genes in estrogen-stimulated liver cells occurs with six of the nine methylation sites examined fully methylated.

(13)C NMR investigation of the superconductor MgCNi(3) up to 800 K.

We report (13)C NMR characterization of the new superconductor MgCNi(3) [T. He et al., Nature (London) 411, 54 (2001)]. We found that both the uniform spin susceptibility and the spin fluctuations show a strong enhancement with decreasing temperature, and saturate below approximately 50 K and approximately 20 K, respectively. The nuclear spin-lattice relaxation rate 1/(13)T(1) exhibits typical behavior for isotropic s-wave superconductivity with a coherence peak below T(c) = 7.0 K that grows with decreasing magnetic field.

S-alkyl-L-thiocitrullines. Potent stereoselective inhibitors of nitric oxide synthase with strong pressor activity in vivo.

Nitric oxide synthase catalyzes the oxidation of a guanidino nitrogen of L-arginine to nitric oxide with concomitant formation of citrulline. Enzyme activity is inhibited by a variety of N omega-monosubstituted L-arginine analogs including N omega-alkyl-, N omega-amino-, and N omega-nitro-L-arginine derivatives. We report here that both constitutive and inducible isoforms of nitric oxide synthase are strongly inhibited by S-alkyl-L-thiocitrullines (N delta-(S-alkyl)isothioureido-L-ornithines) with n-alkyl groups of one to three carbons. These compounds represent a novel class of inhibitors and are the most potent nitric oxide synthase-inhibiting amino acids described to date. Inhibition is reversible, stereoselective, and competitive with L-arginine. Spectral studies show no direct interaction of inhibitor sulfur with heme iron, a result in contrast to that seen previously with the parent compound, L-thiocitrulline. The S-alkyl-L-thiocitrullines have strong pressor activity in normotensive control rats; S-methyl-L-thiocitrulline reverses hypotension in a rat model of septic peritonitis and in dogs administered endotoxin. These latter findings suggest that the inhibitors may have therapeutic utility in treating hypotension due to the overproduction of nitric oxide.

Prostaglandins in inflammatory bone pathology: mechanism and therapeutic benefit of etodolac.

To investigate the role of PGE2 in the development of bone and joint pathology in rat adjuvant arthritis, hindlimb paws were evaluated by calcified tissue histologic techniques focusing on histochemical visualization of cartilage and bone lesions. Case studies of hindlimbs from normal, adjuvant arthritic, and etodolac-treated arthritic rats demonstrated the association of disease severity with inflammation, chondromalacia, replacement of adipose bone marrow with a fibroid marrow, osteoclastic bone resorption, synovial cysts, and pannus formation within the joints. Extensive periosteal intramembranous bone formation was temporally associated with joint destruction and medullary tissue pathology. In vivo data were correlated with in vitro effects of inflammatory mediators (IL-1, PGE2) on bone resorption. Etodolac blocked bone explant PGE2 accumulation at concentrations of 10(-7) M and higher, and inhibited bone resorption at concentrations of 10(-5) M and higher. The data indicate that in vitro and in vivo models of bone metabolism are well correlated regarding prostaglandin synthesis; that the inflammatory mediator PGE2 is largely responsible for the involvement of skeletal tissue in the adjuvant arthritis model; and that the effects of etodolac are specifically mediated by its ability to inhibit PGE2 accumulation in vivo.