Spin-stripe density varies linearly with the hole content in single-layer Bi2+xSr2-xCuO6+y cuprate superconductors.

We have performed inelastic neutron scattering measurements on the single-layer cuprate Bi(2+x) Sr(2-x) CuO(6+y) (Bi2201) with x = 0.2, 0.3, 0.4, and 0.5, a doping range that spans the spin-glass to superconducting phase boundary. The doping evolution of low energy spin fluctuations (11

Hidden itinerant-spin phase in heavily overdoped La(2-x)Sr(x)CuO4 superconductors revealed by dilute Fe doping: a combined neutron scattering and angle-resolved photoemission study.

We demonstrated experimentally a direct way to probe a hidden propensity to the formation of a spin-density wave in a nonmagnetic metal with strong Fermi surface nesting. Substituting Fe for a tiny amount of Cu (1%) induced an incommensurate magnetic order below 20 K in heavily overdoped La(2-x)Sr(x)CuO(4). Elastic neutron scattering suggested that this order cannot be ascribed to the localized spins on Cu or doped Fe. Angle-resolved photoemission revealed a strong Fermi surface nesting inherent in the pristine La(2-x)Sr(x)CuO(4) that likely drives this order. Our finding presents the first example of the long-sought "itinerant-spin extreme" of cuprates, where the spins of itinerant doped holes define the magnetic ordering ground state; it complements the current picture of cuprate spin physics that highlights the predominant role of localized spins at lower dopings.

Lymphocyte DNA adducts and polymorphism in the DNA repair enzyme XPD.

The effect of genetic polymorphism of DNA repair enzyme on the DNA adduct levels was evaluated in this study. We explored the relationship between polymorphism in the nucleotide excision repair enzyme XPD and DNA adduct levels in lymphocytes. Lymphocyte DNA adducts were measured by a (32.)

Coordinated reassembly of the basement membrane and junctional proteins during corneal epithelial wound healing.

PURPOSE: To characterize changes in the localizations of the basement membrane protein laminin-1 and of adhesion proteins of intercellular junctions during wound healing after epithelial ablation in the rat cornea. METHODS: Epithelial ablation was performed with an excimer laser. Rats were killed immediately, 12 hours, 24 hours, 3 days, or 4 weeks after ablation, and corneal cryosections were subjected to two-color immunofluorescence staining with antibodies to laminin-1 and antibodies to connexin43 for gap junctions, desmoglein 1 or 2 (desmoglein 1 + 2) for desmosomes, or E-cadherin for adherens junctions. Sections were also stained with antibodies to occludin for examination of tight junctions. RESULTS: Laminin-1 was detected in the basement membrane, connexin43 in the basal cell layer, desmoglein 1 + 2 in the wing cell layer, E-cadherin in all cell layers, and occludin in the wing and superficial cell layers of the intact corneal epithelium. Laminin-1 immunostaining was not detected at the leading edge of migrating epithelial cells until 24 hours after ablation. Expression of connexin43 and desmoglein 1 + 2 coincided with the reappearance of laminin-1, whereas that of E-cadherin and occludin was apparent regardless of the absence or presence of laminin-1. Epithelial remodeling was complete after 4 weeks. The basement membrane was re-established, and the expression patterns for all the adhesion proteins were identical with those characteristic of the intact cornea. CONCLUSIONS: Actively migrating epithelial cells no longer manifested gap junctions and desmosomes in the wounded area with no basement membrane. Re-establishment of the basement membrane coincided with reassembly of these intercellular junctions, suggesting that the presence of the basement membrane may be required for their reformation in the rat cornea.

Formation of acyl radical in lipid peroxidation of linoleic acid by manganese-dependent peroxidase from Ceriporiopsis subvermispora and Bjerkandera adusta.

Lipid peroxidation by managanese peroxidase (MnP) is reported to decompose recalcitrant polycyclic aromatic hydrocabon (PAH) and nonphenolic lignin models. To elucidate the oxidative process, linoleic acid and 13(S)-hydroperoxy-9Z,11E-octadecadienoic acid [13(S)-HPODE] were reacted with MnPs from Ceriporiopsis subvermispora and Bjerkandera adusta and the free radicals produced were analyzed by ESR. When the MnPs were reacted with 13(S)-HPODE in the presence of Mn(II), H2O2 and tert-nitrosobutane (t-NB), the ESR spectrum contained a sharp triplet of acyl radical (aN = 0.81 mT). Formation of acyl radical was also observed in the reactions of Mn(III)-tartrate with 13(S)-HPODE and with linoleic acid, but the latter reaction occurred explosively after an induction period of around 30 min. Reactions of MnP with linoleic acid in the presence of Mn(II), H2O2 and t-NB gave no spin adducts while addition of t-NB after preincubation of linoleic acid with MnP/Mn(II)/H2O2 for 2 h gave spin adducts of carbon-centered (aN = 1.53 mT, aH = 0.21 mT) and acyl (aN = 0.81 mT) radicals. In contrast to linoleic acid, methyl linoleate and oleic acid were not peroxidized by MnP and chelated Mn(III) within a few hours, indicating that structures containing both the 1,4-pentadienyl moiety and a free carboxyl group are necessary for inducing the peroxidation in a short reaction time. These results indicate that MnP-dependent lipid peroxidation is not initiated by direct abstraction of hydrogen from the bis-allylic position during turnover but proceeds by a Mn(III)-dependent hydrogen abstraction from enols and subsequent propagation reactions involving the formation of acyl radical from lipid hydroperoxide. This finding expands the role of chelated Mn(III) from a phenol oxidant to a strong generator of free radicals from lipids and lipid hydroperoxides in lignin biodegradation.

Inter-individual variation of smoking-related DNA adducts in lymphocytes-relationship to mRNA levels for CYP1A1 and DNA repair enzymes.

The measurement of DNA adducts is a useful indicator for environmental carcinogen exposure monitoring. To clarify the effect of metabolic activation and DNA repair system on the inter-individual variation of DNA adduct levels, aromatic DNA adducts and mRNA expression of metabolic and repair enzymes were measured in 43 human lymphocytes. Aromatic DNA adducts were measured by the nuclease P1 postlabelling method. The metabolic activation enzyme; cytochrome P4501A1 (CYPIA1), and the repair enzyme; excision repair cross complimenting gene (ERCC1), and the xeroderma pigmentosum C group cell gene (XPCC), mRNA expression were measured by the reverse transcription-PCR method. The mean adduct levels were 1.01 ± 0.49 in 43 subjects. There was a positive correlation between DNA adducts and CYP1A1 mRNA (r = 0.33, p = 0.12). DNA adduct levels had a positive correlation with ERCC1 (r = 0.35, p = 0.03) and a negative correlation with XPCC mRNA levels (r = -0.28, p = 0.07). We found Brinkman index, CYP1A1 genotypes, CYP1A1 mRNA and XPCC mRNA as a predictor for log DNA adduct levels in multivariate analysis. Metabolic activation and the repair system may explain the inter-individual variation of DNA adducts in lymphocytes.

Extracellular lipid peroxidation of selective white-rot fungus, Ceriporiopsis subvermispora.

Ceriporiopsis subvermispora is capable of decomposing lignin without penetration of enzymes into wood cell walls. To elucidate the mechanism of lignolysis at a site far from enzymes, peroxidation of low molecular mass compounds produced by this fungus was analyzed. C. subvermispora produced free 9,12-octadecadienoic, 9-octadecenoic, 11-octadecenoic, hexadecanoic and octadecanoic acids, predominantly at an early stage of cultivation on wood meal cultures. In prolonged cultivation period after 2 weeks, the amount of intact fatty acids decreased with increasing organic hydroperoxide and TBARS production. These results suggest that lignin degradation by C. subvermispora is related to extracellular lipid peroxidation.

3-Methylglutaconic aciduria type I: clinical heterogeneity as a neurometabolic disease.

3-Methylglutaconic (3-MGC) aciduria with 3-methylglutaconyl-CoA hydratase deficiency (3-MGC aciduria type I) is a rare inherited metabolic disease of L-leucine catabolism. We describe a 9-month-old Japanese boy with this disorder who showed progressive neurological impairments presented as quadriplegia, athetoid movements and severe psychomotor retardation from 4 months of age. This finding indicates the existence of clinical heterogeneity in 3-MGC aciduria type I, suggesting it may present as a neurometabolic disease.

The antiatherogenic effect of nifedipine on intramural small coronary arterial lesions in cholesterol-fed rabbits.

The objective of this study was to examine the suppressive effect of nifedipine on intramural coronary arterial lesions in cholesterol-fed rabbits. Each rabbit in Groups A (n=6) and B (n=5) was fed a 0.3% cholesterol diet and was orally administered nifedipine (40 mg/day) or placebo. Each rabbit in Groups C (n=5) and D (n=6) was fed a 0.5% cholesterol diet and was orally administered nifedipine (40 mg/day) or placebo. The serum concentrations of total cholesterol (TC) were determined at 1-week intervals to calculate the integrated values. The lesion induction ratio was defined as the ratio of intramural coronary arteries 50-150 microm in diameter with arterial lipoidosis to the total number of arteries of the same diameter. There were no significant differences between the nifedipine-treated and placebo groups in either the integrated TC or lesion induction ratio in either the 0.3% and 0.5% cholesterol-fed rabbits. This study demonstrates that nifedipine does not suppress atherogenesis in the intramural small coronary arteries of cholesterol-fed rabbits.

Childhood multiple sclerosis treated with plasmapheresis.

We report a case of multiple sclerosis in a 7-year-old boy. He experienced three episodes in 8 months and was repeatedly treated with a high dose of methylprednisolone. During the third episode, to avoid the side effects associated with frequent high doses of steroid, we substituted plasmapheresis for methylprednisolone, initially performing it for 3 days and continuing it every 2 to 3 weeks according to the fluctuating values of antinuclear antibody. The patient improved markedly after initiation of plasmapheresis and has been relapse-free for more than 18 months. The effectiveness of plasmapheresis for treatment of multiple sclerosis in adults is variable and has seldom been reported in children. Our case suggests that plasmapheresis as an alternative therapy is useful for steroid-dependent or severe types of multiple sclerosis even in childhood, especially when its chronic course is assessed by antinuclear antibody titers.

Treatment of branch retinal arterial occlusion with sodium ozagrel, a thromboxane A2 synthetase inhibitor.

A 47-year-old woman with branch retinal arterial occlusion treated with sodium ozagrel is described. The patient presented with acute visual field loss in her right eye. Blood tests demonstrated the elevation of beta-thromboglobulin and platelet factor 4. Sodium ozagrel, a thromboxane A2 synthetase inhibitor, 160 mg daily was administered for 14 days. This treatment prevented exacerbation of retinal arterial thrombosis and produced a marked improvement in the visual field loss. Sodium ozagrel may be a useful drug in the treatment of acute retinal arterial occlusion thought to be caused by thrombosis.

[Neurotrophic keratopathy--studies on substance P and the clinical significance of corneal sensation].

Neurotrophic keratopathy, which often follows damage to the trigeminal nerve, is clinically characterized by various types of epithelial disorders and melting of corneal stroma. To understand both the pathology of neurotrophic keratopathy and the physiological significance of corneal sensation, we investigated both the cellular and molecular functions of a sensory neurotransmitter, substance P, in corneal epithelial cells. Our findings prompted us to try a new mode of treatment for neurotrophic keratopathy. Substance P, a member of the tachykinin family, is an 11-amino-acid peptide. In an organ culture system using rabbit corneas, substance P alone had no effect on corneal epithelial migration. In the presence of insulin-like growth factor-1 (IGF-1), however, substance P synergistically facilitated corneal epithelial migration in proportion to the concentration of substance P or of IGF-1. Other neurotransmitters (acetylcholine, norepinephrine, serotonin etc.) or tachykinins (neurokinin A, eledoisin etc.) did not show this synergistic effect with IGF-1. Among receptors for the tachykinin family (NK-1, NK-2, or NK-3) only the NK-1 receptor system was involved in the synergistic effect of substance P and IGF-1 on corneal epithelial migration. IGF-1 affected neither the binding constant nor the number of sites of substance P receptors in corneal epithelial cells, suggesting that the synergistic effect was not regulated at the receptor level. Various extracellular signals activate the intracellular signal transduction system, thus amplifying specific biological functions. We found that the addition of inhibitors of protein kinase C or tyrosine kinase clearly inhibited the synergistic effect of substance P and IGF-1 on corneal epithelial migration, demonstrating that protein kinase C and tyrosine kinase are involved in the synergistic effect. During corneal epithelial wound healing, epithelial cells must attach to a provisional, extracellular fibronectin matrix. We previously reported that interleukin 6 and epidermal growth factor (EGF) facilitate corneal epithelial wound healing by activating the expression of fibronectin receptor (integrin). Reverse transcription-polymerase chain reaction (RT-PCR) revealed that substance P and IGF-1 increased expression of mRNA for integrins alpha 5 and beta 1 in cultured corneal epithelial cells and also increased the number of cells that attached to a fibronectin matrix. These findings strongly suggest that substance P and IGF-1 synergistically increase corneal epithelial migration by activating the expression of integrin. Tachykinins share a five amino acid sequence, phenylalanine-free amino acid-glycine-leucine-methionine amide (FXGLM), at the C-terminus. Studying substance P, we found that a four amino acid sequence at the C-terminus, FGLM, was the minimum amino acid sequence for the synergistic effect on corneal epithelial migration. Structurally similar tetrapeptides mimicking other members of the tachykinin family isoleucine-glycine-leucine-methionine amide (IGLM), valine-glycine-leucine-methionine amide (VGLM), tyrosine-glycine-leucine-methionine amide (YGLM), and the tripeptide glycine-leucine-methionine amide (GLM) did not have any synergistic effect with IGF-1. Based on these findings in vitro, we investigated the effect of eye drops containing substance P plus IGF-1 or FGLM plus IGF-1 on the epithelial wound closure of rabbit corneas in vivo. Both combinations significantly facilitated corneal epithelial wound closure. In a clinical setting, the administration of substance P plus IGF-1 effectively treated corneal epithelial defects in a patient with Riley-Day syndrome, a disease in which corneal epithelial defects persist because of loss of corneal sensation and hypolacrimation. In a patient with neurotrophic keratopathy due to trigeminal nerve paralysis following surgery, eye drops containing FGLM plus IGF-1 eliminated superficial punctate staining. (ABSTRACT TRUNCATED)

Abrupt aggravation of atrioventricular block and syncope in hypertrophic cardiomyopathy.

A 10 year old girl with hypertrophic cardiomyopathy (HCM) developed high grade atrioventricular (A-V) block unexpectedly, which instantly led to syncope; she required a permanent pacemaker. High grade A-V block, a rare complication of HCM, relates closely to syncope or sudden death in this disease and if progressive the use of cardiac pacing should be considered without delay.

Seronegative myasthenia gravis associated with atonic urinary bladder and accommodative insufficiency.

We report a 20-year-old female with generalized myasthenia gravis (MG) who developed atonic urinary bladder and accommodative insufficiency. Although her sera did not contain antibodies to either nicotinic acetylcholine receptor (AChR) or voltage-gated calcium channels, a positive intravenous edrophonium test and a waning phenomenon on electromyographic studies indicated a diagnosis of seronegative MG. Myasthenic symptoms as well as urinary incontinence and impaired near vision disappeared with slight sequelae after corticosteroid therapy and total removal of the hyperplastic thymus. These symptoms recurred during a tapering course of corticosteroids, and improved again with an increased dose. Therefore, in this patient, the neuromuscular transmission of muscarinic type of AChR in the smooth muscles was also affected. This patient provides insight into the mechanisms by which some smooth muscles are involved in MG.

Identification of an unusual structure in the Drosophila melanogaster transposable element copia: evidence for copia transposition through an RNA intermediate.

The Drosophila melanogaster transposable element copia is usually 5 kb long with long terminal repeats (LTRs), and its major transcripts are a full-length 5-kb RNA and a 2-kb RNA. We have previously shown that the 2-kb RNA is generated through splicing. Here, we have cloned a genomic intronless copia using an oligodeoxyribonucleotide probe which is specific for the junction of the two exons. The unusual copia is bounded by two LTRs and lacks precisely the intron of the 2-kb copia RNA. Identification of genomic intronless copia strongly suggests that copia transposes through an RNA intermediate. Moreover, we have found that copia virus-like particles (VLPs), in which reverse transcription of copia RNA seems likely to occur, packages the spliced copia RNA much less efficiently than the full-length copia RNA. This result leads to the suggestion that much lower copy number of genomic intronless copia, as compared with that of 'normal' copia, may be responsible for the inefficient packaging of the spliced copia RNA into the VLP.