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Biomedical subjects

Y Hayashi

Publications and source records attributed to Y Hayashi.

At least 235 records · Page 13Linked to original sources
PubMed2001

[Anti-GQ1b IgG-negative case of overlapping Fisher's and Gullain-Barré syndromes after Campylobacter jejuni (PEN 19) enteritis].

We described a 70-year-old woman with overlapping Fisher's syndrome (FS) and Guillain-Barré syndrome (GBS), from whom Campylobacter jejuni had been isolated. In typical FS as well as GBS with ophthalmoplegia and acute ophthalmoparesis without ataxia, serum anti-GQ1b IgG antibody often is detected and ophthalmoplegia is characterized by the predominant abducens palsy. This patient, however, showed marked oculomotor nerve disturbance. Serum anti-GQ1b IgG antibody was negative and IgG antibodies against GM1, GM1b, and GD1a were strongly positive. Although FS and overlap of FS/GBS have been reported to be associated with PEN2 of C. jejuni, the isolate from our case belonged to PEN 19. C. jejuni serotype may be associated with clinical manifestations and anti-ganglioside antibody species.

Aged↗
PubMed2001

[Factors inducing severe osteoporosis].

Among various factors advancing bone loss, immobility is the most remarkable cause to deteriorate osteoporosis. In the animal experiment, we could be obvious that immobilization of femur by suspension of rat tail reduced calcium content of bone through diminished blood circulation of bone, especially in femoral neck. In stroke patients who are often suffered from femoral neck fracture, bone mineral measurement revealed bone loss in paralyzed limb, in addition to healthy limb. Bone loss in both limbs in the hemiplegic patient and the fragility of femoral neck are caused by decrease of daily activity. Low nutrition in the patients who are took gastrectomy and suffered from rheumatoid arthritis is pointed out as the other factor inducing severe osteoporosis.

English Abstract↗
PubMed2001

[Diagnosis of osteoporosis].

For the purpose of treatment of osteoporosis, we should not increase only bone mass, but should increase the quality of patient's life through decreasing the uncomfortable symptoms of osteoporosis and prevalence of fractures. For diagnosis of osteoporosis, we have to distinguish the other spinal diseases by the detailed physical examination, in addition to acquire the daily habit of nutrition and exercises. Radiographical findings of spines and laboratory examinations including measurement of deoxy-pyridinoline are important to diagnose osteoporosis.

English Abstract↗
PubMed2000

The 5-HT(1A) receptor agonist, 8-OH-DPAT, attenuates stress-induced anorexia in conjunction with the suppression of hypothalamic serotonin release in rats.

The effect of the selective 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on stress-induced anorexia and serotonin (5-HT) release in the rat hypothalamus was studied with brain microdialysis. Subcutaneous injection of 8-OH-DPAT (1 mg/kg) significantly attenuated the immobilization-induced anorexia for 3 h, but had no effect during the following 9 h. Injection of 8-OH-DPAT itself had no effect on basal release of 5-HT, while it significantly blocked the immobilization-induced 5-HT release in the lateral hypothalamus. The results suggest that 8-OH-DPAT attenuated the stress-induced anorexia through the activation of 5-HT(1A) autoreceptors in dorsal raphe nucleus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Changes in expressions of proinflammatory cytokines IL-1beta, TNF-alpha and IL-6 in the brain of senescence accelerated mouse (SAM) P8.

The senescence-accelerated mouse (SAM) is known to be a murine model for accelerated aging. The SAMP8 strain shows age-related deterioration of learning and memory at an earlier age than control mice (SAMR1). In the present study, we investigated the changes in expressions of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the brain of SAMP8. In the hippocampus of 10 months old SAMP8, the expression of IL-1 mRNA was significantly elevated in comparison with that of SAMR1. In both strains of SAMs, increases in IL-1beta protein in the brain were observed at 10 months of age compared with 2 and 5 months. The only differences found between the strain in protein levels were at 10 months and were elevations in IL-1beta in the hippocampus and hypothalamus, and in TNF-alpha and IL-6 in the cerebral cortex and the hippocampus in SAMP8 as compared with SAMR1. However, lipopolysaccharide-induced increases in the expression of these cytokines in brain did not differ between SAMP8 and SAMR1. Increases in expression of proinflammatory cytokines in the brain may be involved in the age-related neural dysfunction and/or learning deficiency in SAMP8.

Aging↗
PubMed2000

Breakdown of Th cell immune responses and steroidogenic CYP11A1 expression in CD4+ T cells in a murine model implanted with B16 melanoma.

The association between the balance of Th1/Th2 cell responses and CYP11A1 expression in CD4+ T cells was investigated in a murine model implanted with highly metastatic B16F10 melanoma cells (B16F10 mice). When 2 x 10(5) cells/mouse of B16F10 cells were inoculated into C57BL/6 mice, Th2 cell responses and pulmonary metastasis were increased. In addition, corticosterone levels in splenic tissue or serum and CYP11A1 mRNA expression (mRNA encoding cholesterol side-chain cleavage p450 enzyme) in CD4+ T cells were increased in these mice. When the anti-corticosterone drug aminoglutethimide (CYP11A1 inhibitor) was administered to B16F10 mice, corticosterone levels in splenic tissue or serum and CYP11A1 mRNA expression were decreased at 14 days after tumor inoculation. In addition, Th1 cell responses were restored and pulmonary metastasis was reduced by aminoglutethimide. These results indicated that the breakdown of Th cell responses and increase of pulmonary metastasis were due to an increase in steroidogenic CYP11A1 mRNA expression in CD4+ T cells. Moreover, it was suggested that promotion of CYP11A1 mRNA expression in Th2 cells was partially involved due to an increase in level of corticosterone in splenic tissue and the breakdown of Th cell responses locally in the splenic tissue, which then affected the maintenance of Th2 cell functions in the microenvironment of tumor-bearing mice.

Aminoglutethimide↗
PubMed2000

HSNF5/INI1 gene mutations in lymphoid malignancy.

hSNF5/INI1 is one of the components of the SWI/SNF multiprotein complex that is necessary for the transcriptional activation of several genes and functions by altering chromatin structure. This gene has been thought to be one of the tumor suppressor genes (TSGs) because deletions or mutations were reported in malignant rhabdoid tumors and atypical teratoid and rhabdoid tumors. To evaluate the hSNF5/INI1 gene as a TSG in lymphoid malignancies, we performed a mutational analysis in 23 patients with non-Hodgkin lymphoma (NHL), 24 with acute lymphoblastic leukemia (ALL), 24 with multiple myeloma (MM), 24 with adult T-cell lymphoma/leukemia (ATLL), and 19 with lymphoid cell lines, by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis. Nonsense and missense mutations were found in 1 NHL case and 2 cell lines. Mutations from this NHL case proved to be somatic in origin. These data indicated that alterations in the hSNF5/INI1 gene might be involved in the pathogenesis of lymphoid malignancies.

Base Sequence↗
PubMed2000

GDP-fucose: beta-galactoside alpha1,2-fucosyltransferase, MFUT-II, and not MFUT-I or -III, is induced in a restricted region of the digestive tract of germ-free mice by host-microbe interactions and cycloheximide.

A shift from sialylation to fucosylation of mucosal glycoconjugates occurred in the mammalian digestive tract in the weaning period, but mice under germ-free conditions were found to express both fucosyl GM1 (FGM1) and fucosyl asialo GM1 (FGA1) in the stomach, cecum and colon, but not in the small intestine. By host-microbe interactions and administration of cycloheximide, FGA1 was quickly induced in the small intestine, but the concentrations of fucosylated glycolipids in the other regions were not altered significantly. Their expression coincided with the activity of GDP-fucose:GA1 alpha(1, 2)-fucosyltransferase (alpha1,2-FT), and we isolated a cDNA with an open reading frame encoding the murine alpha1,2-FT (MFUT-II) of 347 amino acids with a predicted molecular mass of 39.21 kDa. The intraperitoneal injection of cycloheximide induced the mRNA and activity of alpha1,2-FT (MFUT-II) in the small intestine of germ-free mice, whereas no change in the mRNA or activity was observed in the stomach, cecum and colon, indicating that expression of FGA1 in response to microbial colonization or cycloheximide is transcriptionally regulated in a restricted region of the murine digestive tract. At 24 h after the administration of cycloheximide, FGA1 was preferentially produced in the upper half of the duodenal microvilli.

Amino Acid Sequence↗
PubMed2000

Inhibition of neuronal nitric-oxide synthase by calcium/ calmodulin-dependent protein kinase IIalpha through Ser847 phosphorylation in NG108-15 neuronal cells.

We have previously demonstrated that phosphorylation of neuronal nitric-oxide synthase (nNOS) at Ser(847) by Ca(2+)/calmodulin-dependent protein kinases (CaM kinases) attenuates the catalytic activity of the enzyme in vitro (Hayashi Y., Nishio M., Naito Y., Yokokura H., Nimura Y., Hidaka H., and Watanabe Y. (1999) J. Biol. Chem. 274, 20597-20602). In the present study we determined that CaM kinase IIalpha (CaM-K IIalpha) can directly phosphorylate nNOS on Ser(847), leading to a reduction of nNOS activity in cells. The phosphorylation abilities of purified CaM kinase Ialpha (CaM-K Ialpha), CaM-K IIalpha, and CaM-kinase IV (CaM-K IV) on Ser(847) were analyzed using the synthetic peptide nNOS-(836-859) (Glu-Glu-Arg-Lys-Ser-Tyr-Lys-Val-Arg-Phe-Asn-Ser-Val-Ser-Ser-Tyr-Ser- Asp-Ser-Arg-Lys-Ser-Ser-Gly) from nNOS as substrate. The relative V(max)/K(m) ratios of CaM kinases for nNOS-(836-859) were found to be as follows: CaM-K IIalpha, 100; CaM-K Ialpha, 54.5; CaM-K IV, 9.1. Co-transfection of constitutively active CaM-K IIalpha1-274 but not inactive CaM-K IIalpha1-274, generated by mutation of Lys(42) to Ala, with nNOS into NG108-15 cells, resulted in increased Ser(847) phosphorylation in the presence of okadaic acid, an inhibitor of protein phosphatase (PP)1 and PP2A, with a concomitant inhibition of NOS enzyme activity. In addition, this latter decrease could be reversed by treatment with exogenous PP2A. Cells expressing mutant nNOS (S847A) proved resistant to phosphorylation and a decrease of NOS activity. Thus, our results indicate that Ca(2+) triggers cross-talk signal transduction between CaM kinase and NO and CaM-K IIalpha phosphorylating nNOS on Ser(847), which in turn decreases the gaseous second messenger NO in neuronal cells.

Amino Acid Sequence↗
PubMed2000

Decreased protein kinase C-epsilon expression in hypertrophied cardiac ventricles induced by triiodothyronine treatment in the rat.

To examine the effect of thyroid hormone-induced cardiac hypertrophy on PKC expression, changes in the expression of PKC isoforms were studied in hypertrophied cardiac ventricles induced by triiodothyronine (T3) injection in the rat. Injection with T3 for 8 days induced 49% increase in cardiac weight compared to controls. Immunoblot analysis of cardiac ventricular extracts showed the expression of PKC-delta, -epsilon, and -zeta in both control and T3-treated groups. The expression of PKC-epsilon decreased by 40% in hyperthyroid rat cardiac ventricles, while PKC-delta and -zeta expressions were barely affected. PKC-epsilon immunoreactivity decreased in both cytosol and membrane fractions. On the contrary, PKC-epsilon expression did not decrease in the extract of hypertrophied cardiac ventricles produced by aortic banding or aortocaval shunt. These results indicate that thyroid hormone down regulates PKC-epsilon expression in the hyperthyroid-mediated cardiac hypertrophy.

Animals↗
PubMed2000

Autoantigen-specific CD4+CD28low T cell subset prevents autoimmune exocrinopathy in murine Sjögren's syndrome.

Organ-specific autoimmune exocrinopathy resembling Sjögren's syndrome (SS) that spontaneously develops in NFS/sld mutant mice thymectomized 3 day after birth is dependent on Th1-type CD4+ T cells. We previously reported that a cleavage product of 120-kDa alpha-fodrin may be an important autoantigen in the pathogenesis of SS in both an animal model and the patients. We demonstrate that in an animal model of SS with overt exocrinopathy, a unique CD4+ T cell subset expressing CD28low is dramatically increased in spleen cells before the disease onset, but that the CD4+ T cells of diseased mice were virtually all CD28high. We found that the spleen cells in these mice before the disease onset showed a significant increase in autoantigen-specific T cell proliferation. Analysis of in vitro cytokine production by spleen cells indicated, before the disease onset, severely impaired production of IL-2 and IFN-gamma in the animal model, whereas high levels of IL-4 were observed. Expression of cytokine genes, including IL-4, IL-10, and TGF-beta, was detected in FACS-sorted CD4+CD28low T cells by RT-PCR analysis. Transfer of CD4+CD28low T cells into the animal model actually prevented the development of autoimmune lesions including autoantibody production. These results suggest that a CD4+CD28low T cell subset that is continuously activated by an organ-specific autoantigen may play a regulatory role in the development of organ-specific autoimmune disease in an animal model of SS.

Adoptive Transfer↗
PubMed2000

Analyses of Gerstmann-Straussler syndrome with 102Leu219Lys using monoclonal antibodies that specifically detect human prion protein with 219Glu.

Two monoclonal antibodies that specifically detect human prion protein (PrP) were developed. The epitope of both antibodies was mapped using fusion proteins of glutathione-S-transferase and PrP peptides to the C-terminal region encompassing the polymorphic 219 residue. The antibodies recognized human PrP with 219Glu but not that with 219Lys. The unique property of the antibodies was utilized to determine the allelic origin of abnormal PrP deposited in the brain of a patient with Gerstmann-Straussler syndrome (GSS) with 102Leu/219Lys encoded by the same allele. Abnormal PrP was exclusively of mutant allelic origin, suggesting that 219Lys may be permissive to the formation of abnormal PrP in GSS. The antibodies may help to explore the relationship of 219Glu/Lys polymorphism to the pathogenesis of human prion diseases.

Amino Acid Substitution↗
PubMed2000

5-Fluorouracil induces apoptosis through the suppression of NF-kappaB activity in human salivary gland cancer cells.

Activation of the transcription factor NF-kappaB results in protection against apoptosis, and the chemotherapeutic agent 5-Fluorouracil (5-FU) exerts its cytotoxic effect through the induction of apoptosis. Thus, we examined whether 5-FU could induce apoptosis through the suppression of NF-kappaB activity. We found that upon treatment of a human salivary gland cancer cell line (cl-1) with 5-FU, the NF-kappaB activity was suppressed in a time-dependent manner. This inhibition was mediated by a prevention of the degradation of the inhibitory IkappaB-alpha protein. In addition, the expression of TRAF-2 and cIAP-1, which are transcriptionally regulated by NF-kappaB and function as anti-apoptotic molecules through the interruption of caspase pathway, was also inhibited by 5-FU. Finally, the activity of caspase-8 and caspase-3 showed a significant increase in response to 5-FU. By flow cytometric analysis, 5-FU did not affect the expression level of Fas on the cell surface. Thus, our results suggest that one of the molecular mechanisms involved in 5-FU-induced apoptosis in cl-1 cells may be due to the suppression of NF-kappaB activity, resulting in the activation of the pro-apoptotic pathway.

Antimetabolites, Antineoplastic↗
PubMed2000

'Double-Drugs'--a new class of prodrug form of an HIV protease inhibitor conjugated with a reverse transcriptase inhibitor by a spontaneously cleavable linker.

We designed and synthesized a new series of prodrug-type anti-HIV agents consisting of a peptidomimetic HIV protease inhibitor conjugated with a nucleoside reverse transcriptase inhibitor in an effort to enhance the antiviral activity. For the conjugation, a series of linkers that conjoin the two different classes of inhibitors have been investigated. Conjugates using a succinyl amino acid linker were shown to release the parent components via the spontaneous imide formation at a faster rate compared to conjugates using a glutaryl amino acid linker, as expected from the energetically favorable cyclization to the five-membered ring. Herein, we report a new 'double-drug' 4b (KNI-1039) with a glutarylglycine linker, which exhibited extremely potent anti-HIV activity compared with that of the individual components.

Anti-HIV Agents↗
PubMed2000

Myopathy phenotype of transgenic mice expressing active site-mutated inactive p94 skeletal muscle-specific calpain, the gene product responsible for limb girdle muscular dystrophy type 2A.

A defect of the gene for p94 (calpain 3), a skeletal muscle-specific calpain, is responsible for limb girdle muscular dystrophy type 2A (LGMD2A), or 'calpainopathy', which is an autosomal recessive and progressive neuromuscular disorder. To study the relationships between the physiological functions of p94 and the etiology of LGMD2A, we created transgenic mice that express an inactive mutant of p94, in which the active site Cys129 is replaced by Ser (p94:C129S). Three lines of transgenic mice expressing p94:C129S mRNA at various levels showed significantly decreased grip strength. Sections of soleus and extensor digitorum longus (EDL) muscles of the aged transgenic mice showed increased numbers of lobulated and split fibers, respectively, which are often observed in limb girdle muscular dystrophy muscles. Centrally placed nuclei were also frequently found in the EDL muscle of the transgenic mice, whereas wild-type mice of the same age had almost none. There was more p94 protein produced in aged transgenic mice muscles and it showed significantly less autolytic degradation activity than that of wild-type mice. Although no necrotic-regenerative fibers were observed, the age and p94:C129S expression dependence of the phenotypes strongly suggest that accumulation of p94:C129S protein causes these myopathy phenotypes. The p94:C129S transgenic mice could provide us with crucial information on the molecular mech-anism of LGMD2A.

Animals↗
PubMed2000

Beneficial effects of MET-88, a gamma-butyrobetaine hydroxylase inhibitor in rats with heart failure following myocardial infarction.

Myocardial ischemia can cause myocardial infarction and as a consequence, heart failure. 3-(2,2,2-trimethylhydrazinium) propionate (MET-88) inhibits gamma-butyrobetaine hydroxylase and has cardioprotective effects on the ischemic heart. We now examined the effects of MET-88 in rats with congestive heart failure following myocardial infarction. Congestive heart failure was produced by left coronary artery ligation in rats. MET-88 at 100 mg/kg/day was orally administered from the 2nd day after surgery. We performed a survival study for 181 days, and measured ventricular remodeling, cardiac function, and myocardial high-energy phosphate levels after treatment for 20 days. MET-88 prolonged survival with a median 50% survival of 103 days compared to 79 days for the heart-failure control rats. The expansion of the left ventricular cavity (ventricular remodeling) in heart-failure rats was prevented by treatment with MET-88, and the effect of MET-88 was similar to that of captopril at 20 mg/kg. MET-88 attenuated the rise in right atrial pressure in heart-failure rats and augmented cardiac functional adaptability against an increased load. Also, MET-88 improved the myocardial energy state in heart-failure rats. The present results indicate that MET-88 improves the pathosis in rats with heart failure induced by myocardial infarction.

Adenosine Diphosphate↗