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M Nishihara

Publications and source records attributed to M Nishihara.

At least 37 records · Page 2Linked to original sources
PubMed2000

Genetic dissection of vasculitis in MRL/lpr lupus mice: a novel susceptibility locus involving the CD72c allele.

An MRL/MpJ strain of mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), composed of genomes derived from LG/J, AKR/J, C3H/Di and C57BL/6J mice, develops systemic vasculitis coincidentally with other collagen diseases, but a C3H/HeJ-lpr/lpr (C3H/lpr) strain does not. In a genome-wide screening of the MRL background genes mediating susceptibility to collagen diseases using N2 progeny mice MRL/lpr x (MRL/lpr x C3H/lpr)F1, we previously found that each collagen disease is controlled by a different set of genes. To clarify the candidate genes for vasculitis, we extended the linkage analysis of renal vasculitis to a larger number of N2 mice and to F2 intercross mice. Two distinct recessive susceptibility loci for vasculitis were mapped on chromosome (Chr) 4 at D4Mit89 and D4Mit147 in both progenies. The former was a novel locus for lupus phenotypes, which involved the MRL allele CD72(c) in contrast to the C3H allele CD72(b). The one on Chr 3 was a recessive locus which had an inhibitory effect on vasculitis. From their composition these loci seemed to be derived from AKR/J (for one) and LG/J (for another two) strains, and appeared to act in an additive manner on the development of vasculitis, indicating that vasculitis in MRL/lpr mice is inherited in a polygenic manner.

Alleles↗
PubMed2000

Efficacy of HSP72 induction in rat liver by orally administered geranylgeranylacetone.

It is well known that heat-shock proteins (HSPs) have a cytoprotective function as "molecular chaperones" when cells are exposed to several stress conditions. Geranylgeranylacetone (GGA) is an antiulcer drug that was developed in Japan and it has recently been reported to induce HSP72 in rat gastric mucosa. In this experiment, we investigated the induction of HSP72 in rat liver in response to oral administration of GGA and assessed its ability to induce tolerance to warm ischemic injury by this approach. We prepared donor rats by orally administering GGA to them and compared HSP72 expression in graft liver, survival rates, and serum TNF-alpha concentrations after liver transplantation with the findings in controls. The survival rates were significantly increased when the livers were obtained from donor rats given GGA. Western blotting revealed expression of HSP72 in graft livers given GGA, and the serum TNF-alpha levels were significantly suppressed in the rats given GGA. Oral administration of GGA induced HSP72 in graft livers, and they were better able to tolerate warm ischemic injury. Oral administration of GGA appears to provide a promising new strategy for preventing ischemia-reperfusion injury.

Administration, Oral↗
PubMed2000

Neurotransmitter contents in the retina of RCS rat.

BACKGROUND: Retinitis pigmentosa is a hereditary disease characterized by gradually developing degeneration of photoreceptors. The Royal College of Surgeons (RCS) rat is an experimental model of retinitis pigmentosa. However, there is a paucity of information concerning neurotransmitter contents in the retina of RCS rats. Thus, we determined the retinal contents of neurotransmitters in RCS rats at 4 and 23 weeks postnatally and in age-matched congenic control rats. METHODS: Dopamine (DA) and acetylcholine (ACh) were electrochemically measured by high-performance liquid chromatography (HPLC). Neuroactive amino acids, including gamma-aminobutyric acid (GABA) and taurine, were determined by means of an HPLC-precolumn derivatization method. RESULTS: Contents of DA, ACh, glutamate, aspartate and GABA in the retina of RCS rats 4 weeks postnatally were within normal ranges. At 23 weeks, the retinal contents of DA, glutamate and aspartate in the RCS rats were significantly lower than in the age-matched control rats, while the contents of ACh and GABA were unaffected even at this later stage. On the other hand, the retinal content of glycine in the RCS rats at 23 weeks was significantly higher than that in the age-matched control rats. It is interesting to note that the content of taurine in the RCS rats had already decreased at 4 weeks postnatally and the decrease was more marked at 23 weeks. CONCLUSION: The decrease in taurine content is probably the first sign of degeneration revealed by the retinal neurotransmitters of RCS rats.

Acetylcholine↗
PubMed2000

Straight-chain fatty alcohols in the hyperthermophilic archaeon Pyrococcus furiosus.

Two straight-chain fatty alcohols (n-hexadecanol and n-octadecanol) were found in the neutral lipid fraction extracted from Pyrococcus furiosus cells. They were identified by thin-layer and gas-liquid chromatography, mass and infrared spectra, and chemical modification. The fatty alcohols accounted for 54% of the neutral lipid of the cell.

Chromatography, Thin Layer↗
PubMed2000

Suppression of copulatory behavior by intracerebroventricular infusion of antisense oligodeoxynucleotide of granulin in neonatal male rats.

Sexual dimorphism of the rodent brain is manifested by the epigenetic action of gonadal steroids. Our previous research identified the granulin (grn) precursor gene as a sex steroid-inducible gene, which was shown to be expressed more abundantly in male than female neonates at the mediobasal hypothalamic area. Grn is a 6-kDa polypeptide promoting or inhibiting the growth of epithelial cells and hematocytes in vitro. In this study, effects on male sexual behavior of male were pursued under conditions in which grn gene expression was suppressed during the critical period. To this end, an antisense oligodeoxynucleotide (ODN) of the grn precursor gene was designed, incorporated into inactivated Sendai virus (HVJ)-liposome complexes, and infused into the third ventricle of 2-day-old male rats. Two different control treatments were used: the first consisted of a control sequence ODN that had little homology to known mRNAs; the second of vehicle (HVJ-liposome) alone. After maturation, animals treated with antisense ODN of grn displayed significantly lower scores than control males on various parameters assessing sexual behavior; i.e., mount, intromission, and ejaculation. The antisense ODN, however, did not affect body growth or serum concentrations of testosterone and luteinizing hormone. Further, there was no significant difference in the volume of the sexual dimorphic nucleus of the preoptic area between antisense ODN-treated and control animals. It was shown that inadequate expression of the grn gene in the brain of male neonatal rats during the critical period suppressed the induction of some type of male sexual behavior, suggesting the grn was involved in the process of masculinization of the rat brain.

Animals↗
PubMed2000

Perfusion of the hypothalamic paraventricular nucleus with N-methyl-D-aspartate produces thromboxane A2 and centrally activates adrenomedullary outflow in rats.

We applied a microdialysis technique for the measurement of hypothalamic thromboxane B2, a stable metabolite of thromboxane A2, in urethane-anesthetized rats. Perfusion with N-methyl-D-aspartate (1.5 and 2.5mM) of the paraventricular nucleus by microdialysis probe concentration-dependently elevated the levels of thromboxane B2 in this region and plasma levels of catecholamines. The elevation of adrenaline was much more marked than that of noradrenaline. Pretreatment with dizocilpine maleate (0.1 mM), a non-competitive antagonist of N-methyl-D-aspartate receptors, of the paraventricular nucleus by microdialysis probe attenuated the N-methyl-D-aspartate (1.5 mM)-induced elevations of both thromboxane B2 and plasma catecholamines. Intracerebroventricular administration of furegrelate (250 microg/animal), a thromboxane A2 synthase inhibitor, also abolished the responses evoked by N-methyl-D-aspartate. These results indicate that N-methyl-D-aspartate applied into the paraventricular nucleus produces thromboxane A2 in this region and elevates plasma levels of catecholamines, especially adrenaline. Thromboxane A2 produced in this hypothalamic nucleus is probably involved in the N-methyl-D-aspartate-induced central adrenomedullary outflow.

Adrenal Medulla↗
PubMed2000

U-46619, a selective thromboxane A2 mimetic, inhibits the release of endogenous noradrenaline from the rat hippocampus in vitro.

Possible roles of thromboxane A2 (TXA2) in the release mechanism of hippocampal noradrenaline (NA) were examined in vitro. Slices or crude synaptosomes prepared from the rat hippocampus were superfused with modified Krebs-Ringer solution. Application of 20 mM KCl for 5 min increased the release of NA from the slices, and this release was consistently reproduced. Application of U-46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F2alpha), a specific TXA2 mimetic, just before the second KCl (20 mM) stimulation decreased the KCl-evoked NA release in a concentration-dependent manner (10-100 microM). This U-46619 (50 microM)-induced inhibition of NA release was abolished by 10 microM SQ29548, a specific TXA2 receptor antagonist. In experiments with hippocampal crude synaptosomes, however, KCl (20 and 40 mM)-evoked release of NA was not attenuated by U-46619 (100 microM). Furthermore, the inhibitory effect of U-46619 (50 microM) in the sliced preparations was not modified by 100 microM (-)-bicuculline, a GABA(A)-receptor antagonist. The present results indicate that U-46619 inhibits the release of NA from the rat hippocampus by activation of TXA2 receptors. Activation of TXA2 receptors probably excites an unidentified but not GABAergic neuron system, thereby inhibiting the NA release from the rat hippocampus.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Effect of taurine in rat milk on the growth of offspring.

The physiological significance of taurine in milk in the growth of rat pups was investigated. Our results confirmed that taurine was at an exceptionally high concentration in rat milk during the lactational period, especially for the first few days after birth. Pups taking no milk from natural dams but from foster mothers at an advanced lactational period showed a slower growth rate. Intraperitoneal administration of taurine to the foster mothers in the first five days restored this growth retardation. On the other hand, intraperitoneal administration of beta-alanine, a transport antagonist of taurine, to the natural dams through the lactational period induced a slower growth rate of pups. This beta-alanine treatment to dams increased beta-alanine concentration, but did not decrease taurine concentrations in milk, and serum taurine concentration in the pups receiving this milk was elevated. Direct administration of beta-alanine to pups also increased the serum taurine concentrations dose-dependently. Beta-alanine administration to pups significantly decreased [3H]taurine incorporation into all the organs examined, and in contrast. [3H]taurine concentrations in serum and urine were elevated. Thus, beta-alanine inhibited taurine incorporation into cells and accelerated taurine excretion into either urine or milk. Serum IGF-I levels in pups receiving beta-alanine either directly or via their mothers was significantly lower than those in control pups. Cumulatively, taurine ingestion from milk at an early lactational period seems critical for normal growth of rat neonates due to its role in maintaining normal serum IGF-I levels.

Animals↗
PubMed2000

Expression of cysteine sulfinate decarboxylase mRNA in rat mammary gland.

Our previous report demonstrated that high concentration of taurine is present in rat milk for the first few days of lactation and plays an important role in the body growth of rat pups. In the present study, gene expression of rate-limiting enzyme for taurine biosynthesis, cysteine sulfinate decarboxylase (CSD) were examined in rat mammary gland. By RT-PCR, CSD mRNA was found to be expressed in rat mammary gland like that in the liver. The expression level of CSD mRNA in the mammary gland was higher in the earlier lactational stage (days 1 and 6 of lactation) than that in the later lactational stage (day 14). CSD mRNA expression in the mammary gland of non-pregnant rats was only a trace level. By in situ hybridization analysis, CSD mRNA was demonstrated in the epithelial cells of the mammary gland. These results suggest that high concentrations of taurine in the milk are at least partially resulted from de novo synthesis of taurine in mammary gland epithelial cells and that the expression pattern of CSD mRNA may be responsible for the changes in taurine levels in the milk during a lactational period.

Animals↗
PubMed2000

Development of obesity in transgenic rats with low circulating growth hormone levels: involvement of leptin resistance.

BACKGROUND: Human growth hormone (hGH) transgenic (TG) rats have been produced in our laboratory. These TG rats are characterized by low circulating hGH levels, virtually no endogenous rGH secretion, and massive obesity. OBJECTIVE: To elucidate how energy balance and leptin sensitivity contributed to the establishment of this obesity. DESIGN AND METHODS: Food intake, locomotor activity and leptin concentrations in serum and cerebrospinal fluid were measured in TG rats and their non-transgenic littermates (control). The effect of intraperitoneal and intracerebroventricular injection of leptin on food intake and body weight gain was also examined. RESULTS: An increase in food intake and a decrease in locomotor activity were observed from 4 and 7 weeks of age, respectively, in the transgenic rats compared with control. Serum leptin concentrations of the transgenic rats were more than twice as high as those of control rats and were associated with an increased white adipose tissue mass and ob gene expression. Intraperitoneal injection of leptin significantly decreased food intake and body weight gain in control rats, but not in transgenic rats. Leptin concentration in the cerebrospinal fluid of transgenic rats was not different from that of control rats, and intracerebroventricular injection of leptin was similarly effective in reducing food intake and body weight gain as it was in control rats. CONCLUSIONS: These results suggest that the transgenic rats, whose GH secretion is suppressed, develop obesity due to early onset of an increase in food intake and a decrease in locomotor activity with leptin resistance resulting from deteriorating leptin transport from peripheral blood to cerebrospinal fluid.

Adipose Tissue↗
PubMed2000

Genetic basis of the complex pathological manifestations of collagen disease: lessons from MRL/lpr and related mouse models.

The pathological findings in collagen disease including systemic lupus erythematosus show complex lesions such as glomerulonephritis, systemic vasculitis, polyarthritis, sialoadenitis, etc. Moreover, some cases of collagen disease are categorized into overlapping syndromes. It is still controversial whether such diversity and similarity of pathological manifestations among the collagen disease depends on ambiguity in diagnosis or is an intrinsic quality of the collagen diseases themselves. In this paper, we reviewed this subject focusing on a series of our genetic studies of murine models of collagen disease, MRL strains of mice with a deficit in Fas-mediated apoptosis, which spontaneously develop glomerulonephritis, systemic vasculitis, polyarthritis and sialoadenitis. We observed that each lesion was controlled by a different set of genes and they appeared to act in an additive manner on the development of each lesion. We conclude that various disease categories in collagen disease will be a result of the combination of polygenes.

Animals↗
PubMed2000

[A case of neurogenic bladder due to neuro-Behçet disease].

Behçet disease is a systemic vasculitis of unknown cause with variable clinical features. The central nervous system may also be involved in about 10% of the patients with Behçet disease. Half of them show marked central nervous system symptoms and are diagnosed as neuro-Behçet disease. Voiding symptom is seen in about 5% of the patients with neuro-Behçet disease. We report a case of neuropathic vesico-urethral dysfunction in a 39-year-old man with neuro-Behçet disease. Its radiological and urodynamic features and treatment are also presented with some discussion.

Adult↗
PubMed2000

Genetic basis of autoimmune disease in MRL/lpr mice: dissection of the complex pathological manifestations and their susceptibility loci.

MRL/MpJ-lpr/lpr (MRL/lpr) mice spontaneously develop various forms of autoimmune disease in the same individuals, including glomerulonephritis, polyarteritis, arthritis and sialoadenitis. An MRL recombinant congenic strain of mice bearing the gld gene, MRLiMpTn-gld/gld (MRL/gld), also develops lesions similar to those in MRL/lpr mice. The lpr and gld genes are a Fas deletion mutant and a Fas ligand mutant, respectively. Thus, autoimmune disease in these mice seemed to be a single gene disease involving the complex pathological manifestations as pleiotropy. However, comparative studies with C3H/HeJ and C57BL/6J strains of mice bearing lpr or gld revealed that these lesions developed only in mice with an MRL background. Moreover, these lesions were genetically segregated among MRL/lpr x (MRL/lpr x C3H/lpr)F1 mice. This indicates that an MRL strain has particular gene(s) affecting the development of each lesion. Association studies of each lesion with polymorphic microsatellite markers using backcross mice revealed that gene loci responsible for each lesion exist at different chromosomal positions and have additive and hierarchical properties of polygenic inheritance for some of the lesions. We conclude that the complex pathological manifestations of autoimmune disease are under the control of different combinations of polygenes.

Animals↗
PubMed1999

Expression of stromal cell-derived factor-1/pre-B cell growth-stimulating factor receptor, CXC chemokine receptor 4, on CD34+ human bone marrow cells is a phenotypic alteration for committed lymphoid progenitors.

We found that the stromal cell-derived factor-1/pre-B cell growth-stimulating factor receptor, CXC chemokine receptor 4 (CXCR4), is expressed on human CD34+ bone marrow (BM) cells. Stringently FACS-sorted CD34+CXCR4+ BM cells completely lack myeloid, erythroid, megakaryocytic, and mixed colony-forming potential (myeloid progenitors), but give rise to B and T lymphoid progenitors, whereas CD34+CXCR4- BM cells can generate colonies formed by myeloid progenitors and can also develop into these lymphoid progenitors. Therefore, expression of CXCR4 on CD34+ BM cells can allow lymphoid progenitors to be discriminated from myeloid progenitors. Because CD34+CXCR4+ cells are differentiated from CD34+CXCR4- cells, multipotential progenitors located in the BM are likely to be negative for CXCR4 expression. CXCR4 seems to be expressed earlier than the IL-7R and terminal deoxynucleotidyl transferase during early lymphohemopoiesis. These results suggest that the expression of CXCR4 on CD34+ BM cells is one of the phenotypic alterations for committed lymphoid progenitors.

Adult↗
PubMed1999

Fas/Fas ligand system in prolactin-induced apoptosis in rat corpus luteum: possible role of luteal immune cells.

The prolactin (PRL) surge in cycling rats during the proestrous afternoon is an inducer of apoptotic cell death in luteal cells. This luteolytic action of PRL is peculiar, because PRL may be categorized as a survival factor, if other known physiological functions of PRL are taken into account. Here we analyzed the underlying molecular/cellular mechanisms of this PRL-induced apoptosis. Corpora lutea (CL) were prepared from the ovary on the proestrous day and cultured with or without PRL (2 microg/ml). An addition of PRL to the culture medium induced DNA breakdown in the nuclei of cells mostly identified as steroidogenic by 3beta-HSD activity staining, and the number of 3beta-HSD-positive cells were significantly decreased, indicating the induction of apoptotic cell death by PRL among luteal cells in culture. Next, the expression of membrane form-Fas ligand (mFasL) in the luteal cell lysate was quantified, because Fas receptor is known to have an exact physiological role in luteolysis. An addition of PRL increased the expression of mFasL. Immunostaining and TUNEL assay on regressing CL revealed that both CD3-positive cells and FasL-positive cells were co-localized in the regions where apoptosis convergently occurred. Moreover, an addition of concanavalin A (ConA), a T-cell specific activator, to the culture mimicked the PRL action by inducing apoptosis in luteal cells and enhancing the expression of mFasL. These data suggest that the CD3-positive T lymphocyte in the CL is at least one of the PRL-effector cell species during the process of luteolysis in rats, and that FasL expression of these cells is upregulated by PRL.

Animals↗
PubMed1999

Pretreatment of crude pancreatic islets with mitomycin C prolongs graft survival time in xenogeneic rat-to-mouse model.

BACKGROUND: Rejection of pancreatic islet grafts is still a serious problem. We evaluated the effect of mitomycin C (MMC) on the survival of crude islets grafts after xenogeneic islet transplantation. METHODS: WS (RT1k) rat islets pretreated with various concentrations of MMC (0, 1, 3.2, 10, 32, 50, 100, 320, and 1,000 microg/ml) were transplanted into C57BL/6 mice with streptozotocin-induced diabetes. In vivo graft function was assessed by a daily measurement of nonfasting blood glucose concentration in each animal. We also examined the separate effect of MMC on purified islets and contaminants present in the crude islet preparation. RESULTS: MMC at doses of 10, 32, 50, and 100 microg/ml resulted in a significant prolongation of the mean graft survival time from a control of 12.4+/-2.5 days to 23+/-7.4, 17.5+/-5.4, 25.5+/-14.7, and 26.7+/-8.9 days, respectively. Deterioration of glucose metabolism was noted when the dose exceeded 32 microg/ml, whereas at 320 microg/ ml, MMC failed to restore normoglycemia. Prolongation of survival time of crude islets was the result of its effect on islets and contaminant components of the crude islet preparation. In vitro study showed that MMC treatment at a higher concentration than 10 microg/ml reduces the stimulatory as well as proliferative capacity of lymph node cells. CONCLUSIONS: Pretreatment of pancreatic islets with MMC at 10 microg/ml prolongs xenograft survival without deterioration of in vivo graft function. This novel treatment modality represents a new strategy for the modulation of immunity of islets and contaminants in crude islet preparations.

Animals↗