Superconducting energy gap and antiferromagnetic spin fluctuations in the superconductor YNi2B2C: An NMR study.
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Biomedical subjects
Publications and source records attributed to T Oda.
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Urinary trypsin inhibitor (UTI) is one of the Kunitz-type protease inhibitors in human. Little is known about its anti-inflammatory functions other than protease inhibition. We studied the effect of UTI on gene expression of interleukin-8 (IL-8), an inflammatory cytokine. UTI inhibited IL-8 gene expression induced by lipopolysaccharide (LPS) in HL60 cells. The IL-8 concentrations in the cells and medium after LPS stimulation increased time-dependently in the absence of UTI, but did not increase in the presence of UTI. On the other hand, UTI did not inhibit either the synthesis or the release of IL-8 induced by the calcium ionophore A23187. UTI inhibited increase of cytosolic Ca2+ stimulated by LPS but not by A23187. Our results suggest that the inhibition by UTI is due to its effect on the cell membrane involved in regulating Ca2+ influx.
Horseshoe crab hemocyte lysate responds to (1-->3)-beta-D-glucans, initiating an enzymatic cascade, which culuminates in clot formation. We have purified to homogeneity the serine protease zymogen factor G, which is directly activated by (1-->3)-beta-D-glucans and which initiates the hemolymph clotting cascade. Factor G is a heterodimeric protein composed of two noncovalently associated subunits alpha (72 kDa) and beta (37 kDa). In the presence of (1-->3)-beta-D-glucans such as curdlan and paramylon, factor G is autocatalytically activated to an active serine protease named factor G. This activation is accompanied by limited proteolysis of both subunits: the 72-kDa subunit alpha is cleaved to 55-kDa and 17-kDa fragments, and the 37-kDa subunit beta is shortened to 34 kDa. Longer incubations with (1-->3)-beta-D-glucans result in cleavage of the 55-kDa fragment to 46 kDa and the 34-kDa fragment to 32 kDa, with concomitant loss of amidase activity. Reconstitution experiments using purified proteins participating in the hemolymph clotting cascade demonstrate that factor G is capable of activating proclotting enzyme directly, resulting in the conversion of coagulogen to coagulin gel. Thus, purified factor G is shown to be the primary initiator of the (1-->3)-beta-D-glucan-sensitive coagulation pathway in the horseshoe crab hemocyte lysate.
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Twenty-six patients who had an infected nonunion or segmental defect of the tibia with skin loss were treated in one stage with debridement and a free vascularized osteocutaneous fibula or iliac graft. Successful control of infection, closure of skin defects, and incorporation of bone union were achieved in all patients except one. In an average follow-up of 39 months, no recurrence of infection was seen. There were four stress fractures of the grafted fibula; these healed within 2 months with cast immobilization. Graft hypertrophy was common in the fibula grafts, but it took 1 1/2 years for hypertrophy of the graft to be strong enough to remove external supports without stress fracture or an additional cancellous bone graft. The use of a one-stage free vascularized osteocutaneous graft for the management of infected bone defects of the tibia with skin loss is effective because extensive debridement can remove all devitalized and infected tissue and can increase vascularity in the region of infection and osseous defect to enhance antibiotic delivery.
We investigated the effects of various ceramide (Cer) analogs and related sphingolipids on the cytotoxicities of modeccin, ricin, Pseudomonas toxin, and diphtheria toxin in various cell lines. The most pronounced protective effect by C6Cer, a short-chain cell-permeable Cer analog, was observed in modeccin cytotoxicity in Vero, BER-40, and MDCK cells, whereas the cytotoxicity of diphtheria toxin was not affected by any of the ceramide analogs tested. C6Cer did not affect the binding and internalization of ricin and modeccin in Vero and BER-40 cells. C2Cer and C8Cer also protected against modeccin cytotoxicity, albeit less effectively than C6Cer. However, related sphingolipids including sphingosine, sphingomyelin, lactosylceramide, C18Cer (the naturally occurring ceramide), and dihydro C6Cer had no effect. A correlation was found between the ability of ceramides to inhibit bulk protein secretion and the inhibition of modeccin cytotoxicity by ceramides. Among Cer analogs tested, C6Cer, the most potent inhibitor of modeccin cytotoxicity, strongly inhibited bulk protein secretion in Vero, BER-40, and MDCK cells. PtK1 cells, which were not protected by ceramides against toxins, were resistant to ceramide-induced inhibition of bulk protein secretion. These results confirm that Cer may modulate the intracellular transport of proteins through the Golgi complex. Such Cer-sensitive processes may be involved in the intoxication of cells by plant and bacterial toxins, especially modeccin.
Clusterin (apoJ), a multifunctional apolipoprotein made by cells in the brain and many other locations, is associated with aggregated amyloid beta-peptide (A beta) in senile and diffuse plaques of Alzheimer's disease (AD). We observed that purified human serum clusterin partially blocked the aggregation of synthetic A beta 1-42, as shown by centrifugal assays (14,000g x 10 min) and by atomic force (scanning probe) microscopy. Slowly sedimenting A beta complexes were formed in the presence of clusterin, which included aggregates > 200 kDa that resist dissociation by low concentrations of SDS. Clusterin enhanced the oxidative stress caused by A beta, as assayed by oxidative stress in PC12 cells with MTT, which is widely used to estimate neurotoxicity. These indications of enhanced neurotoxicity by the MTT assay were observed in the highly aggregated rapidly sedimenting fraction, but also in more slowly sedimenting "soluble" forms. This novel activity of slowly sedimenting A beta may enhance the neurotoxicity of A beta deposits in AD brains, because soluble complexes have a potential for diffusing to damage distal neurons.
We describe an insert mutation in the prion protein (PrP) gene in a Japanese family line that encodes six octapeptide repeats. This is the second report to date of an inherited prion disease with a 144-base pair insertion, although the order of the repeat sequences differ from that reported for the disease in an English family line. The clinical features, like those of the English patients, were characterized by a slowly progressive generalized dementia with some neurological signs and cortical focal symptoms. Postmortem examination disclosed diffuse atrophy of cerebral gray matter and the cerebellar cortex; histologically, there were marked patchy and regional neuronal loss with astrocytosis in the frontal cortex, amygdala and hippocampus and PrP-immunoreactive plaques in the molecular layer of the cerebellum. These plaques were different from typical kuru plaques. The prion disease in the present Japanese family line is compared with that in the English family line.
We describe a technique for repairing the ventricular septal perforation using porcine pericardium tailored in a conical shape. This technique may allow a good operating view and facilitate suturing to the left ventricular cavity.
This study characterizes the effect of transforming growth factor (TGF) beta 1 on clusterin expression in rat brain cells. 24 h after an acute unilateral intracerebroventricular infusion of TGF-beta 1, clusterin mRNA prevalence was increased in astrocytes that contained immunoreactive (IR) glial fibrillary acidic protein (GFAP). TGF-beta 1 selectively induced clusterin mRNA in astrocytes, as no clusterin mRNA was detected in neurons, oligodendrocytes, or microglia. TGF-beta 1 induced a bilateral increase in clusterin mRNA per astrocyte. Astrocyte hypertrophy (GFAP-IR area) was only increased on the ipsilateral side. In pure astrocyte cultures, TGF-beta 1 (200 pM) decreased clusterin mRNA levels and the rate of clusterin RNA transcription. However, in cultures of astrocytes that contained microglia and oligodendrocytes (mixed glia cultures), TGF-beta 1 caused a dose-dependent increase in astrocytic clusterin mRNA levels. The astrocytes that responded to TGF-beta 1 included two GFAP-IR subtypes, type 1 and 2. TGF-beta 1 increased clusterin protein in the conditioned medium from cultured glia, in either monotypic or mixed glial cultures. Thus, TGF-beta 1 and heterotypic cell interactions influence clusterin expression by astrocytes and may be important to the role of clusterin in multiple sclerosis, AIDS, and Alzheimer's disease.
This study examines the relationship between the levels of apolipoprotein E (apoE) and apolipoprotein J (apoJ, also designated as clusterin) as a function of apoE genotype in the hippocampus and cortex of Alzheimer disease (AD) subjects. These two lipophilic proteins which are involved in the maintenance of lipid homeostasis are both synthesized in the brain by astrocytes. Results indicate a reduction of apoE levels in the hippocampus and frontal cortex that is proportional to the apoE4 allele dose. Conversely, apoJ (clusterin) levels were found to increase proportionately to the number of apoE4 allele dose. These results suggest a compensatory induction of apoJ (clusterin) in the brain of apoE4 AD subjects showing low brain levels of apoE.
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1000 serum samples from blood donors were tested for human parvovirus B19 (B19) DNA by a nested PCR assay: six samples were positive for B19 DNA. The frequency was 1/167 (0.6%), considerably higher than previous surveys (0.004-0.03%). Five of the six samples were also positive for anti-B19 IgM, indicating an acute phase of infection. It is recommended to screen for B19 DNA in blood products to prevent transfusion mediated viral infection for those susceptible such as immunocompromised patients and pregnant women.
The clinical and serological course of a haemophilic baby who was transfused with 160 ml of blood containing the hepatitis C virus (HCV) (0.70 Meq. ml-1) on the sixth-post-natal day is described. He is the infant of an HCV-negative mother. One month after the transfusion, there was a marked increase in HCV RNA and a small amount of HCV antibody was detected. This case provides evidence that a newborn is capable of producing HCV antibodies.
We examined sera from 10 patients with hemolytic uremic syndrome (HUS) and 51 controls, with and without diarrhea, for antibodies to Escherichia coli lipopolysaccharides (LPS) O157, O111 and O26 using the indirect hemagglutination (IHA) assay. A significant rise (to a titer of > or = 2560) in IHA antibody to O157 LPS was detected in eight of the 10 HUS patients, to O111 in two patients, one of whom showed concomitantly an antibody rise to O157, but to O26 in no patients. The IHA titers fell rapidly after the acute phase of the illness. Of the control sera 15 (29.4%) non-specifically agglutinated uncoated sheep red blood cells (SRBC) at a titer of > or = 80, six (3.9%) at > or = 320 and the maximum was 640. In spite of the relatively low level of non-specific agglutination the IHA appeared to be a useful screening method to identify verotoxin-producing E. coli infections at the early stage of HUS because the titers were clearly higher than non-specific agglutination and the assay is easy to perform and gives results quickly. Artificial carriers are being considered for use in place of SRBC to diminish the non-specific hemagglutination.
We report here a case of type 1 mesangiocapillary glomerulonephritis as well as a case of mesangial proliferative glomerulonephritis associated with streptococcal skin infection superimposed on atopic dermatitis. Both were endemic occurrences of postinfectious glomerulonephritis developed after repeated dirty-skin treatments for atopic dermatitis performed by unauthorized individuals under unsanitary conditions. Of 20 patients who were similarly treated and subsequently admitted to our hospital because of skin infection and fever, 8 (40%) showed urinary abnormalities. Four patients had renal dysfunction with acute nephritic onset. Almost all showed a decrease in CH50 values and an increase in levels of antistreptolysin O and IgE. In the 2 cases presented here, the disease eventually regressed in association with improvement of the skin infection. Although the occurrence of postinfectious glomerulonephritis has recently become uncommon, we must take care to note urinary abnormalities as early as possible in order to prevent the progression of glomerulonephritis.
Induction of mitochondrial serine: pyruvate aminotransferase (SPT) in rat liver by administration of glucagon was studied quantitatively by immunoblot analysis and cryoimmunogold electron microscopy. Immunoblot analysis revealed that two daily injections of glucagon produced marked increase of SPT protein mass to a level as much as 18 times that of the untreated rat. Cryoimmunogold electron microscopic analysis showed that the labeling density of the mitochondria increased in a parallel manner. Thus the induction of SPT analyzed by two methods showed an excellent correlation with a relative correlation coefficient of 0.98, indicating that the induction of SPT can be analyzed quantitatively by immunogold electron microscopy on cryoultrathin sections.
We have previously reported the inhibitory effects of diethylstilbestrol (1) and optically active indenestrol derivatives on microtubule polymerization in vitro and their disruptive effect on cytoplasmic microtubules and cytotoxicity in cultured Chinese hamster V79 cells. In the present study, the cytotoxicities of (+-)-diethylstilbestrol oxide (2), (+)-, (-)- and (+-)-monomethyl ethers (4) of 2, (+-)-dimethyl ether (5) of 2, diethylstilbestrol pinacolone (3), E,E-dienestrol (6), Z,Z-dienestrol (7), meso-hexestrol (8), a mixture of (1R,1'S)4-hydroxyhexestrol and (1R,1'S)4'-hydroxyhexestrol (9), and the 4-hydroxy derivative (10) of diethylstilbestrol dimethyl ether were investigated in Chinese hamster V79 cells. The results indicated that the cytotoxic activity of 10 was the strongest of the compounds tested, although its activity was the almost same as that of 1. Moreover, as the activity of (-)-4 was greater than those of 2 and 1 monomethyl ethers, the effect of 4 on cytotoxic activities was elucidated. In conclusion, the present results indicate that the cytotoxic activities of hydroxylated metabolites are greater than those of each mother compound, although epoxidation of 1 leads to a product which can be broken down more readily than the parent compound.