DOI： 10.1093/alcalc/agz091

PubMed

researchmap

Language：English  

In Japan, it is possible to generate chimeric animals from specified embryos by combining animal blastocysts with human pluripotent stem (PS) cells (animal-human PS chimera). However, the production of animal-human PS chimeras has been restricted because of ethical concerns, such as the development of human-like intelligence and formation of humanized gametes in the animals, owing to the contributions of human PS cells to the brain and reproductive organs. To solve these problems, we established a novel blastocyst complementation technology that does not contribute to the gametes or the brain. First, we established GFP-expressing mouse embryonic stem cells (G-mESCs) in which the Prdm14 and Otx2 genes were knocked out and generated chimeric mice by injecting them into PDX-1-deficient blastocysts. The results showed that the G-mESCs did not contribute to the formation of gametes and the brain. Therefore, in the PDX-1-deficient mice complemented by G-mESCs without the Prdm14 and Otx2 genes, the germline was not transmitted to the next generations. This approach could address concerns regarding the development of both human gametes and a human-like brain upon mouse blastocyst complementation using human stem cells.

DOI： 10.1538/expanim.18-0173

PubMed

researchmap

Publishing type：Research paper (scientific journal)  

Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD), a primary cause of mortality in patients with RA, has limited treatment options. A previously established RA model in D1CC transgenic mice aberrantly expressed major histocompatibility complex class II genes in joints, developing collagen II-induced polyarthritis and anti-cyclic citrullinated peptide antibodies and interstitial pneumonitis, similar to those in humans. Molecular hydrogen (H2) is an efficient antioxidant that permeates cell membranes and alleviates the reactive oxygen species-induced injury implicated in RA pathogenesis. We used D1CC mice to analyse chronic lung fibrosis development and evaluate H2 treatment effects. We injected D1CC mice with type II collagen and supplied them with H2-rich or control water until analysis. Increased serum surfactant protein D values and lung densities images were observed 10 months after injection. Inflammation was patchy within the perilymphatic stromal area, with increased 8-hydroxy-2ʹ-deoxyguanosine-positive cell numbers and tumour necrosis factor-α, BAX, transforming growth factor-β, interleukin-6 and soluble collagen levels in the lungs. Inflammatory and fibrotic changes developed diffusely within the perilymphatic stromal area, as observed in humans. H2 treatment decreased these effects in the lungs. Thus, this model is valuable for studying the effects of H2 treatment and chronic interstitial pneumonia pathophysiology in humans. H2 appears to protect against RA-ILD by alleviating oxidative stress.

DOI： 10.1111/jcmm.14603

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND AIM: Alcohol dehydrogenases (ADHs) 1 and 3 are responsible for systemic alcohol metabolism. The current study investigated the contribution of liver ADH1 and ADH3 to the metabolic pharmacokinetics of chronic alcohol consumption (CAC). METHODS: The 9-week-old male mice of different ADH genotypes (wild-type [WT], Adh1-/- , and Adh3-/- ) were administered with 10% ethanol solution for 1 month, followed by acute ethanol administration (4.0 g/kg). The alcohol elimination rate (AER), area under the blood alcohol concentration curve (AUC), and the maximum blood alcohol concentration (Cmax ) were calculated. The liver content, activity, and mRNA levels of ADH were evaluated. RESULTS: Chronic alcohol consumption increased the AER and reduced the AUC in all ADH genotypes. The increased ADH1 content was correlated with AER in WT mice but not in the Adh3-/- mice. Similarly, the increased ADH3 content was also correlated with AER in both WT and Adh1-/- mice. The Cmax was significantly higher in Adh3-/- control mice than in WT control mice. It decreased in the Adh1-/- mice by CAC along with an increase in the ADH3 content. CONCLUSIONS: Alcohol dehydrogenases 1 and 3 would accomplish the pharmacokinetic adaptation to CAC in the early period. ADH1 contributes to the metabolic pharmacokinetics of CAC with a decrease in AUC in conjunction with an increase of AER by increasing the enzyme content in the presence of ADH3. ADH3 also contributes to a decrease in AUC in conjunction with not only an increase in AER but also a decrease in Cmax by increasing the enzyme content.

DOI： 10.1111/jgh.14260

PubMed

researchmap

Language：English   Publisher：Japanese Society of Veterinary Science  

Expression of peroxisome proliferator-activated receptor (PPAR) α was investigated in adiponectin knockout mice to elucidate the relationship between PPARα and adiponectin deficiency-induced diabetes. Adiponectin knockout (Adp−/−) mice were generated by gene targeting. Glucose tolerance test (GTT), insulin tolerance test (ITT), and organ sampling were performed in Adp−/− mice at the age of 10 weeks. PPARα, insulin, triglyceride, free fatty acid (FFA), and tumor necrosis factor α (TNFα) were analyzed from the sampled organs. Adp−/− mice showed impaired glucose tolerance and insulin resistance. Additionally, PPARα levels were decreased and plasma concentration of triglyceride, FFA and TNFα were increased. These data may indicate that insulin resistance in Adp−/− mice is likely caused by an increase in concentrations of TNFα and FFA via downregulation of PPARα.

DOI： 10.1292/jvms.17-0641

Scopus

PubMed

researchmap

DOI： 10.1272/jnms.JNMS.2018_85-52

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

We previously reported that social isolation promotes parental care in sexually naive male mice. This effect was blocked by exposure to chemosensory and auditory social signals derived from males in an adjacent compartment. In the present study, we examined whether the chemosensory signals detected in the vomeronasal organ (VNO) are involved in parental behavior by using mice deficient for a VNO-specific ion channel (Trpc2(-/-))and thus impaired in VNO-input signaling. We housed virgin homozygous Trpc2(-/-) and heterozygous Trpc2(+/-) males for 3 weeks during puberty (5-8 weeks old) alone or in groups of 3-5 males. At 8 weeks of age, the mice were placed with three pups in an observation cage and tested for parental behavior. The Trpc2(-/-) males housed under isolated conditions spent significantly longer in the vicinity of pups than did the Trpc2(-/-) males than had been group housed, whereas no isolation effect was observed in heterozygous Trpc2(+/-) males. Both Trpc2 knockout and isolation housing significantly increased the time males spent licking pups and crouching (arched back posture over pups to enable nursing), whereas only isolation housing increased the incidence of retrieval behavior. These results demonstrated that social signals transmitted not only through the VNO but also from other modalities, independent of each other, suppress the expression of parental behavior during puberty in sexually naive males. (C) 2016 Elsevier Inc All rights reserved.

DOI： 10.1016/j.physbeh.2016.11.004

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Several drug-metabolizing cytochrome P450 (CYP) enzymes exhibit sexual dimorphism depending on the pituitary growth hormone (GH) secretory patterns. However, the mechanism underlying CYP sexual dimorphism remains unclear. We previously established a transgenic (Alb-DsRed2 Tg) rat that expressed red fluorescent DsRed2 protein, particularly in hepatocytes, to visualize cell differentiation and multiplication and found that hepatic DsRed2 expression exhibited sexual dimorphism that was limited to adult males. In this study, we compared the expression patterns between sexual dimorphic Cyps and DsRed2 in Tg rats after experimentally reversing the GH secretory patterns in males and females. Postnatal day 1 male and female Tg rats were gonadectomized and then testosterone propionate (0.25 mg/rat) was subcutaneously administered to ovariectomized females immediately after surgery. Cyp mRNA and DsRed2 expression levels were quantified using RT-PCR and an in vivo imaging system, respectively. GH-dependent Cyps and hepatic DsRed2 expression patterns were reversed in males and females at 9 weeks after birth and were significantly correlated (P<0.05). This suggested that DsRed2 expression in these Tg rats depended on GH secretory patterns. Based on DsRed2 fluorescence, this Tg rat model could become a tool to readily and effectively evaluate changes in GH-dependent Cyp expression.

DOI： 10.1538/expanim.16-0030

PubMed

researchmap

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Nutritional steatohepatitis is closely associated with dysregulation of lipid metabolism and oxidative stress control. ADH3 is a highly conserved bifunctional enzyme involved in formaldehyde detoxification and termination of nitric oxide signaling. Formaldehyde and nitric oxide are nonenzymatically conjugated with glutathione, which is regenerated after ADH3 metabolizes the conjugates. To clarify roles of ADH3 in nutritional liver diseases, we placed Adh3-null mice on a methionine- and choline-deficient (MCD) diet. The Adh3-null mice developed steatohepatitis more rapidly than wild-type mice, indicating that ADH3 protects liver from nutritional steatohepatitis. NRF2, which is a key regulator of cytoprotective genes against oxidative stress, was activated in the Adh3-null mice with liver damage. In the absence of NRF2, the Adh3 disruption caused severe steatohepatitis by the MCD diet feeding accompanied by significant decrease in glutathione, suggesting cooperative function between ADH3 and NRF2 in the maintenance of cellular glutathione level for cytoprotection. Conversely, with enhanced NRF2 activity, the Adh3 disruption did not cause steatohepatitis but induced steatosis, suggesting that perturbation of lipid metabolism in ADH3-deficiency is not compensated by NRF2. Thus, ADH3 protects liver from steatosis by supporting normal lipid metabolism and prevents progression of steatosis into steatohepatitis by maintaining the cellular glutathione level.

DOI： 10.1111/gtc.12237

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ENDOCRINE SOC  

We reported recently that the taste type 1 receptor 3 (T1R3), a subunit of the sweet taste receptor, functions as a cell-surface glucose-sensing receptor in pancreatic beta-cells. In the present study, we investigated the expression of T1R3 in pancreatic islets. mRNA for T1R2 and T1R3 was detected in mouse pancreatic islets. Quantitatively, the mRNA expression level of T1R2 was less than 1% of that of T1R3. Immunohistochemically, T1R3 was abundantly expressed in mouse islets whereas T1R2 was barely detected. Most immunoreactive T1R3 was colocalized with insulin and almost all beta-cells were positive for T1R3. In addition, T1R3 was expressed in some portion of alpha-cells. Immunoreactivity of T1R3 in beta-cells was markedly reduced in fed mice compared to those in fasting mice. In contrast, mRNA for T1R3 was not different in islets of fasting and fed mice. Glucose-induced insulin-secretion was higher in islets obtained from fasting mice compared to those from fed mice. The expression of T1R3 was markedly reduced in islets of ob/ob mice compared to those of control mice. Similarly, the expression of T1R3 was reduced in islet of db/db mice. In addition, the expression of T1R3 was markedly reduced in beta-cells of fatty diabetic rats and GK rats, models of obese and non-obese type 2 diabetes, respectively. These results indicate that T1R3 is expressed mainly in beta-cells and the expression levels are different depending upon the nutritional and metabolic conditions.

DOI： 10.1507/endocrj.EJ14-0221

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Ltd  

Purpose: Ejaculation in the male dog consists of three fractions. Observation of behavior and measurement of heart rate (HR), and plasma noradrenaline (NA) and adrenaline (Ad) concentrations were researched sequentially, and a fundamental examination of the features of sympathetic nerve activity during copulatory behavior induced by the hand method in the male dog was undertaken. Methods: We investigated the breeding capability of male dogs. HR, plasma NA level and plasma Ad levels were measured during ejaculation induced by the hand method. Results: HR was 125.8 ± 6.0 beats/min at rest, and peaked during mounting at 195.2 ± 8.2 beats/min. Moreover, HR at 3 min after the first fraction decreased to values similar to those at rest. Plasma NA and Ad concentrations during copulatory behavior induced by the hand method did not differ significantly from those at rest. However, although there was no significant difference, plasma NA concentration during ejaculation of the third fraction peaked at about 1.8 times the baseline value. Conclusions: In the male dog, excitation of sympathetic nerves of long duration during erection of the penis and ejaculation is questionable. However, inhibition of sympathetic nerves and activation of parasympathetic nerves is thought to occur during erection of the penis and ejaculation. © 2013 The Author(s).

DOI： 10.1007/s12522-013-0165-x

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Background: Our previous studies revealed that application of the inhalation anesthetic, sevoflurane, reversibly repressed the expression of Per2 in the mouse suprachiasmatic nucleus (SCN). We aimed to examine whether sevoflurane directly affects the SCN. Methods: We performed in vivo and in vitro experiments to investigate rat Per2 expression under sevoflurane-treatment. The in vivo effects of sevoflurane on rPer2 expression were examined by quantitative in situ hybridization with a radioactively-labeled cRNA probe. Additionally, we examined the effect of sevoflurane anesthesia on rest/activity rhythms in the rat. In the in vitro experiments, we applied sevoflurane to SCN explant cultures from Per2-dLuc transgenic rats, and monitored luciferase bioluminescence, representing Per2 promoter activity. Bioluminescence from two peripheral organs, the kidney cortex and the anterior pituitary gland, were also analyzed. Results: Application of sevoflurane in rats significantly suppressed Per2 expression in the SCN compared with untreated animals. We observed no sevoflurane-induced phase-shift in the rest/activity rhythms. In the in vitro experiments, the intermittent application of sevoflurane repressed the increase of Per2-dLuc luminescence and led to a phase delay in the Per2-dLuc luminescence rhythm. Sevoflurane treatment did not suppress bioluminescence in the kidney cortex or the anterior pituitary gland. Conclusion: The suppression of Per2-dLuc luminescence by sevoflurane in in vitro SCN cultures isolated from peripheral inputs and other nuclei suggest a direct action of sevoflurane on the SCN itself. That sevoflurane has no such effect on peripheral organs suggests that this action might be mediated through a neuron-specific cellular mechanism or a regulation of the signal transduction between neurons. © 2013 Anzai et al.

DOI： 10.1371/journal.pone.0059454

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Human mercaptolactate-cysteine disulfiduria (MCDU) was first recognized and reported in 1968. Most cases of MCDU are associated with mental retardation, while the pathogenesis remains unknown. To investigate it, we generated homozygous 3-mercaptopyruvate sulfurtransferase (MST: EC 2.8.1.2) knockout (KO) mice using C57BL/6 embryonic stem cells as an animal model. The MST-KO mice showed significantly increased anxiety-like behaviors with an increase in serotonin level in the prefrontal cortex (PFC), but not with abnormal morphological changes in the brain. MCDU can be caused by loss in the functional diversity of MST; first, MST functions as an antioxidant protein. MST possessing 2 redox-sensing molecular switches maintains cellular redox homeostasis. Second, MST can produce H2S (or HS(-)). Third, MST can also produce SOx. It is concluded that behavioral abnormality in MST-KO mice is caused by MST function defects such as an antioxidant insufficiency or a new transducer, H2S (or HS(-)) and/or SOx deficiency.

DOI： 10.1038/srep01986

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Renal fibrosis is a common finding in progressive renal diseases. Matrix metalloproteinases (MMPs) are involved in epithelial-to-mesenchymal transition (EMT). We investigated the role of MMP-2 and the effect of inhibition of MMPs on the development of renal fibrosis. Renal fibrosis was induced in MMP-2 wild-type (MMP-2(+/+)) mice by unilateral ureteral obstruction (UUO). Renal histopathology, EMT-associated molecules, and activity of MMP-2 and MMP-9 were examined during the development of interstitial fibrosis. UUO-renal fibrosis was also induced in MMP-2 deficient (MMP-2(-/-)) and MMP-2(+/+) mice treated with minocycline (inhibitor of MMPs). In MMP-2(+/+) mice, MMP-2 and MMP-9 were expressed in damaged tubules, and their activities increased in a time-dependent manner after UUO. Interstitial fibrosis was noted at day 14, with deposition of types III and I collagens and expression of markers of mesenchymal cells (S100A4, vimentin, alpha-smooth muscle actin, and heat shock protein-47) in damaged tubular epithelial cells, together with F4/80+ macrophage infiltration. Fibrotic kidneys expressed EMT-associated molecules (ILK, TGF-beta 1, Smad, Wnt, beta-catenin, and Snail). In contrast, the kidneys of MMP-2(-/-) mice and minocycline-treated MMP-2(+/+) mice showed amelioration of renal fibrosis with reduced expression of markers of mesenchymal cells in tubular epithelial cells, inhibition of upregulated EMT-associated molecules, and suppression of macrophage infiltration. The results suggested that MMP-2 have a pathogenic role in renal interstitial fibrosis, possibly through the induction of EMT and macrophage infiltration. Inhibition of MMPs may be beneficial therapeutically in renal fibrosis. Laboratory Investigation (2012) 92, 1149-1160; doi:10.1038/labinvest.2012.68; published online 21 May 2012

DOI： 10.1038/labinvest.2012.68

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC VET SCI  

We established the WBN/Kob-Lepr(fa) rat as a new congenic strain for the fa allele of the leptin receptor gene (Lepr). Homozygous (fa/fa) WBN/Kob-Lepr(fa) rats provide a model of non-insulin-dependent diabetes, although its onset is secondary to pancreatitis. In the present study, we compared histopathological observations of pancreatitis in each genotype of this rat, to examine its suitability as a model of pancreatitis. The histopathological findings of the pancreatitis revealed intense changes dependent on age, such as hemorrhage or hemosiderin deposition. The pancreatitis in homozygous (fa/fa) WBN/Kob-Leppr(fa) rats were more severe than those of WBN/Kob rats.

DOI： 10.1292/jvms.11-0168

Web of Science

PubMed

researchmap

DOI： 10.1159/000346569

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Background/Aims: Matrix metalloproteinases (MMPs) are zinc endopeptidases that degrade extracellular matrix and are involved in the pathogenesis of ischemic damage in acute kidney injury (AKI). In the present study, we analyzed the role of MMP-2 in the repair process in ischemic AKI. Methods: AKI was induced in MMP-2 wild-type (MMP-2(+/+)) and MMP-2-deficient (MMP-2(-/-)) mice by 90-min renal artery clamping followed by reperfusion. Renal histology and the activity and distribution of MMP-2 were examined from day 1 to day 14. During the recovery from AKI, MMP-2(+/+) mice were also treated with MMP-2/MMP-9 inhibitor. Results: In both MMP-2(+/+) and MMP-2(-/-) mice, AKI developed on day 1 after ischemia/reperfusion with widespread acute tubular injury, but subsequent epithelial cell proliferation was evident on days 3-7. During the repair process, active MMP-2 and MMP-9 increased in regenerating tubular epithelial cells in MMP-2(+/+) mice on days 7-14, and the tubular repair process was almost complete by day 14. On the other hand, in MMP-2(-/-) mice, less prominent proliferation of tubular epithelial cells was evident on days 3 and 7, and damaged tubules that were covered with elongated and immature regenerated epithelial cells were identified on days 7 and 14. Incomplete recovery of injured microvasculature was also noted with persistent macrophage infiltration. Similarly, treatment with MMP-2/MMP-9 inhibitor resulted in impaired recovery in MMP-2(+/+) mice. Conclusion: MMP-2 is involved in tubular repair after AKI. The use of the MMP-2/MMP-9 inhibitor was a disadvantage when it was administered during the repair stage of ischemic AKI. Treatment with MMP inhibitor for AKI needs to be modified to enhance recovery from AKI. Copyright (C) 2013 S. Karger AG, Basel

DOI： 10.1159/000346569

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

Background/Aims: Preventing internal hemorrhage extends the lifespan of rats with chronic bile duct ligation (CBDL), a common animal model of portal hypertension. We investigated hemodynamics during the early and late stages of cirrhosis caused by CBDL. We also evaluated the hemodynamic influence of NO, which is the chief vasodilator in hyperdynamic syndrome, by administration of an NO synthase inhibitor (N-6-nitro-L-arginine methyl ester: L-NAME; 10 mg/kg).
Animals/Methods: In 24 Sprague-Dawley rats (9 sham rats and 15 CBDL rats), hemodynamics were assessed under conscious and unrestrained conditions 4 and 8 weeks after surgery. Before and 30 minutes after L-NAME administration, the cardiac index (CI) and regional blood flow were measured with the reference sample method using Ce-141- and Sn-113-microspheres (15 mu m in diameter).
Results: A hyperdynamic systemic circulation and splanchnic hyperemia were observed after CBDL, and these changes increased with the progression of cirrhosis. L-NAME significantly diminished the hyperdynamic circulation and also reduced splanchnic hyperemia. In 4-week CBDL rats, a low hemoglobin concentration made an important contribution to the hyperdynamic circulation, and the portal collateral system collapsed when inflow to the portal territory was reduced by L-NAME treatment. In 8-week CBDL rats, systemic hemodynamics were closely linked to both the splanchnic circulation and the renal circulation before and after L-NAME administration, apart from hepatic artery blood flow.
Conclusion: The distinctive hemodynamic changes of portal hypertension were found in 8-week CBDL rats. Thus, 8-week CBDL rats may be a better animal model of human portal hypertension than 4-week CBDL rats. (J Nippon Med Sch 2011: 78: 146-155)

DOI： 10.1272/jnms.78.146

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Matrix metalloproteinases (MMPs) are endopeptidases that degrade extracellular matrix and involved in ischemic organ injuries. The present study was designed to determine the role of MMP-2 in the development of ischemic acute kidney injury (AKI). AKI was induced in MMP-2 wild-type (MMP-2(+/+)) mice by 30, 60, 90, and 120min renal ischemia and reperfusion. Renal histology, expression and activity of MMP-2 and MMP-9, and renal function were examined during the development of AKI. AKI was also induced in MMP-2-deficient (MMP-2(-/-))mice and MMP-2(+/+) mice treated with inhibitor of MMPs (minocycline and synthetic peptide MMP inhibitor). In MMP-2(+/+) mice, MMP-2 and MMP-9 activities increased significantly at 2 to 24 h, peaked at 6 h, after reperfusion. Immunohistochemical analysis identified MMP-2 in the interstitium around tubules and peritubular capillaries in the outer medulla. Acute tubular injury (ATI), including apoptosis and necrosis, was evident in the outer medulla at 24 h, along with renal dysfunction. As ischemia period increases, MMP-2 and MMP-9 activities at 6 h and severity of AKI at 24 h increased depending on the duration of ischemia between 30 and 120min. However, the kidneys of MMP-2(-/-) mice showed minimal ATI; serum creatinine 24 h after reperfusion was significantly low in these mice. Inhibitors of MMPs reduced ATI and improved renal dysfunction at 24 h. We conclude that MMPs, especially MMP-2 have a pathogenic role in ischemia-reperfusion AKI, and that inhibitors of MMPs can protect against ischemic AKI. Laboratory Investigation (2011) 91, 170-180; doi:10.1038/labinvest.2010.174; published online 18 October 2010

DOI： 10.1038/labinvest.2010.174

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT PRESS EDITING CENTRE INC  

Original WBN/Kob male rats commonly develop chronic pancreatitis by the age of 3 months, while diabetes mellitus occurs at 9 months. In contrast, female rats of this strain do not show pancreatitis or diabetes. The WBN/Kob-fatty rat is a homozygous (fa/fa) congenic strain for the fa allele of the leptin receptor gene (Lepr). In WBN/Kob-fatty rats, both females and males provide a model of non-insulin-dependent diabetes with obesity. The leptin receptor fatty gene (Lepr(fa)) induces obesity and hyperphagia. In the present study, we examined the effect of dietary restriction on pancreatitis and diabetes in female WBN/Kob-fatty rats. Five female fatty rats comprised a restricted feeding group with paired-feeding from 3 to 13 weeks of age, and five female lean rats comprised a control group with paired-feeding. At 13 weeks of age, two of the five female fatty rats of the control group developed diabetes mellitus, while no female fatty rats of the restricted feeding group developed diabetes mellitus. At this stage, pathological changes of the pancreas were observed in female fatty rats. All female fatty rats showed severe interlobular, intra-lobular and intra-islet fibrosis. In female fatty rats of the restricted feeding group, pathological changes of the pancreas were milder those of the free-feeding fatty group. Although dietary restriction could not completely prevent pancreatitis in female fatty rats, the development of diabetes was inhibited by its reduction of the severity of pancreatitis.

DOI： 10.1538/expanim.59.623

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aim:
Acute administration of methylene blue (MB) can reverse hypoxemia in patients with hepatopulmonary syndrome (HPS). We evaluated the effect of chronic MB administration in common bile duct-ligated rats, which develop HPS by 5 weeks after surgery.
Methods:
A total of 96 Sprague-Dawley rats were used, including 63 rats with common bile duct ligation (CBDL), 22 sham-operated rats and 11 normal control rats. MB (6 mg/kg) was injected s.c. once a day for 4 weeks. Evaluation of hemodynamics and intrapulmonary vascular dilatation (IPVD), as well as blood sampling for arterial blood gas analysis, were done under conscious and unrestrained conditions. Hemodynamics were assessed by the reference sample method using 141Ce-microspheres (15 mu m in diameter), and IPVD was also determined by i.v. injection of these microspheres. Histological examination of the lungs was done with hematoxylin-eosin staining and immunohistochemical staining for von Willebrand factor or vascular endothelial growth factor.
Results:
Both the arterial oxygen tension and alveolar-arterial oxygen difference were significantly improved in MB-treated CBDL rats. The hyperdynamic circulation and splanchnic hyperemia seen in untreated CBDL rats were also alleviated by MB treatment. However, IPVD was not affected by MB. Histological examination of the lungs indicated that MB treatment reduced the proliferation of alveolar capillary vessels and angiogenesis, leading to improvement of arterial dysoxygenation. Hepatic synthetic and detoxification functions, as well as renal function, were not altered by MB treatment.
Conclusion:
Methylene blue may be a candidate treatment for HPS that does not cause deterioration of hepatic or renal function.

DOI： 10.1111/j.1872-034X.2010.00640.x

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

The WBN/Kob-Lepr(fa) rat is a new congenic strain for the fa allele of the leptin receptor gene (Lepr). Homozygous (fa/fa) WBN/Kob-Lepr(fa) rats provide a model of non-insulin-dependent diabetes with obesity. Here, we describe the characteristics of this new animal model in detail. At 7 weeks of age, both male and female obese WBN/Kob rats showed inflammatory cell infiltration of the pancreas that suggested pan-pancreatitis and an abnormal OGTT. At 3 months of age, both male and female obese WBN/Kob rats developed overt diabetes mellitus associated with severe chronic pancreatitis. In contrast, lean female WBN/Kob rats do not develop pancreatitis or diabetes. In WBN/Kob rats, this mutation might promote the onset of severe pancreatitis, leading to the rapid development of diabetes mellitus. (c) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2007.12.003

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Vascular smooth muscle cell ( VSMC) proliferation is a key event in the progression of arteriosclerosis. Clinical studies show that uremic toxins deteriorate the arteriosclerosis in renal failure patients. Indoxyl sulfate ( IS) is a strong protein-bound uremic toxin, but the effect of IS on VSMC proliferation has not been studied. We examined the effect of IS on rat VSMC proliferation, assessed by a cell counting kit ( 4-[ 3-[4-lodophenyl]-2-4( 4-nitrophenyl)-2H-5-tetrazolio-1, 3-benzene disulfonate] assay) and by [ (3) H] thymidine incorporation in vitro. We further evaluated a contribution of mitogen-activated protein kinase ( MAPK; p44/42 MAPK) to VSMC proliferation by IS. Immunohistochemical staining was performed for VSMCs using antirat organic anion transporter ( OAT) 3 antibody. The mRNA expressions of platelet-derived growth factor ( PDGF)-A and -C chains, and PDGF-beta receptor were evaluated by real-time PCR. IS stimulated the proliferation of VSMCs in a concentration-dependent manner and activated p44/42 MAPK. Concentration of IS needed to stimulate the proliferation of rat VSMC was about 250 mu M, which is compatible with that in the serum of end-stage renal failure patients. PD98059 ( 10 mu M), a selective inhibitor of MAPK/extracellular signal-regulated kinase, inhibited the IS-induced ( 250 mu M) VSMC proliferation and phosphorylation of MAPK. Probenecid ( 0.5 mM), an inhibitor and substrate of OAT, inhibited the IS-induced ( 250 mu M) VSMC proliferation. Rat OAT3 was detected in VSMCs. The mRNA expressions of PDGF-C chain and PDGF-beta receptor were significantly increased by IS. We conclude that IS directly stimulates rat VSMC proliferation and activates MAPK in vitro. This might be one of the mechanisms underlying the progression of atherosclerotic lesions in end-stage renal disease patients.

DOI： 10.1038/sj.ki.5000340

Web of Science

J-GLOBAL

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Aim: The aim of the present study was to compare the hemodynamic features of portal hypertension in rats with early cirrhosis with those of rats with advanced cirrhosis following common bile duct ligation (CBDL). Methods: A total of 53 male Sprague-Dawley rats were used. Hemodynamics were evaluated under conscious and unrestrained conditions 4 weeks and 8 weeks after CBDL. and 4 weeks after a sham operation. Arterial pressure and portal pressure were measured directly via catheters placed in the right femoral artery and main portal vein, respectively. The cardiac index and organ (splanchninc organs, brain, kidneys and lungs) blood flow were determined by the reference sample method using 141Ce-labeled microspheres (15 μm in diameter). Arterial levels of endothelin-1 and nitrate/nitrite, as well as liver function variables, were also determined. Results: Portal pressure was significantly higher 8 weeks after CBDL (15.8±2.1, n=8) than 4 weeks after CBDL (13.9±2.1 mmHg, n=12, p&lt
0.05), and the hyperdynamic circulation of the early period was attenuated (p&lt
0.05). Although hepatic artery blood flow 4 and 8 weeks after CBDL was higher than that after sham operation (p&lt
0.05), portal territory blood flow was not increased. There was a significant positive correlation between portal pressure and portal territory blood flow 8 weeks after CBDL (r=0.822, n=8, p=0.012). In rats with anemia 4 weeks after CBDL, the hemoglobin concentration was negatively correlated with portal territory blood flow (r= - 0.597, n=12, p=0.040). Conclusion: Portal pressure was higher 8 weeks after CBDL than 4 weeks after CBDL and increased with portal territory blood flow, suggesting that portal hypertension is maintained by a mechanism consistent with the forward flow theory. Anemia might exacerbate the hyperdynamic systemic circulation 4 weeks after CBDL.

DOI： 10.1272/jnms.72.217

Scopus

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER TOKYO  

Background: Rats with chronic bile duct ligation (CBDL) and portal vein ligation (PVL) are used as models of portal hypertension. CBDL rats show hypoxemia with intrapulmonary vasodilatation (IPVD), and are recognized as a model of hepatopulmonary syndrome (HPS), while PVL rats are normoxemic. We investigated the differences in arterial oxygenation between these models, and the key factors leading to HPS. Methods: Forty-eight Sprague-Dawley rats were prepared as CBDL or PVL models, or as Sham rats. Arterial oxygenation, hemodynamics (reference sample method), and IPVD were simultaneously evaluated in conscious and unrestrained animals, using Ce-141- or Sn-113-labeled microspheres (15 mu m in diameter), respectively. Endothelin-1 (ET-1) and nitrate/nitrite (end products of nitric oxide; NOx) production by the lung tissue (increment across the lungs) was also determined. Results: The extent of IPVD was similar in both models, but hypoxemia was only observed in CBDL rats. The ET-1 level and the increment in NOx were significantly increased in CBDL rats, and the increment was directly correlated with impairment of oxygenation. Blood flow through the bronchial arteries (anatomical shunting) was increased in CBDL rats, reaching more than three times the level in PVL rats or Sham rats. Conclusions: These results support the hypothesis that NO derived from the lung tissues contributes to hypoxemia, and IPVD appears to be a prerequisite for impaired oxygenation. The considerable increase of anatomical shunting may potentially contribute to impaired oxygenation in CBDL rats.

DOI： 10.1007/s00535-005-1633-9

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

We have recently found the first example of dielectrically controlled optical resolution (DCR). By adjusting the dielectric constant of the solvent used in the resolution process, each optical isomer of (R, S)-alpha-amino-epsilon-caprolactam can be selectively obtained using N-tosyl- (S)-phenylalanine as a chiral selector. The molecular mechanism of DCR has been investigated by comparing the molecular and crystal structures of the optical selector, its target substrate and their diastereomeric salts. Strong hydrophobic interactions between the phenyl rings of the optical selector govern the molecular aggregation of the selectors and form a hydrophilic layer in which molecular recognition takes place. The recognition site in the hydrophilic layer can inherently identify both of the isomers. The dielectric constant of the solvent used in the discrimination process controls the intermolecular interaction which determines the isomer to be selected. The molecular mechanism of DCR disclosed in this study strongly suggests that DCR is not a specific but a general phenomenon. This method can be applicable to a large variety of optical resolution processes.

DOI： 10.1039/b412827c

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Background/Aims: Nitric oxide (NO) has been suggested as the major cause of pulmonary vascular dilatation and hypoxemia in hepatopulmonary syndrome (HPS). The aim of this study was to assess the effect of NO on arterial oxygenation in rats with common bile duct ligation (CBDL rats), a model of HPS.
Methods: Arterial blood gases were measured in 44 CBDL rats and 44 Sham rats under unrestrained conditions. Intrapulmonary shunting was assessed with Ce-141-labeled microspheres (15-mum diameter) and serum nitrate/nitrite levels were measured by HPLC. The effect of NOS inhibition on A-aDO(2) was studied using L-NAME.
Results: A decrease of PaO2 below 82.7 mmHg (the mean value - 2sigma in Sham rats) was seen in 43% of CBDL rats. Intrapulmonary shunting was greater in CBDL rats than in Sham rats (P &lt; 0.001). A correlation between the extent of shunting and A-aDO(2) was found in all animals studied (r = 0.89, P &lt; 0.001, n = 16). Serum levels of nitrate/nitrite increased significantly across the lungs, and the increase was significantly correlated with A-aDO(2) in the total population of animals studied. Administration of L-NAME to CBDL rats achieved a significant improvement of A-aDO(2).
Conclusions: These results suggest that pulmonary vascular dilatation due to NO leads to hypoxemia in CBDL rats. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/S0168-8278(03)00430-6

Web of Science

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Biomedical Research Foundation  

Immunoparameters in mice fed with atherogenic diets for 4 months were examined. In parallel with accelerated thymic involution, a prominent increase in the proportion of IL-2Rβ+ intermediate TCR cells (i.e., extrathymic T cells) was seen in the liver and other immune organs of mice with atherosclerosis. In contrast, NK cells and high TCR cells (i.e., conventional T cells of thymic origin) decreased. The majority of mononuclear cells isolated from the aorta and kidneys in these mice were also found to be intermediate TCR cells. The present results suggest that mice with atherosclerosis have an accelerated pattern of aging of the immune system and that extrathymic T cells may be responsible for the formation of atheroscherotic lesions.

DOI： 10.2220/biomedres.17.265

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Deodorizing effect of ozone was investigated comparing two types of compact ozonizing apparatus made on an experimental basis. The concentrations of ammonia and trimethylamine were examined as an indicator for deodorizing effect of ozone in animal rooms of rats and guinea pigs at laboratory animal facilities of three different universities. Both of the ozonizing apparatus were able to remove ammonia and trimethylamine in animal rooms, with no significant difference in the performance of the two apparatus. © 1995, Japanese Association for Laboratory Animal Science. All rights reserved.

DOI： 10.1538/expanim.44.255

Scopus

PubMed

researchmap

Language：Japanese   Publisher：The Japanese Society of Clinical Pharmacology and Therapeutics  

DOI： 10.3999/jscpt.25.241

researchmap

Other Link： http://search.jamas.or.jp/link/ui/1995000224

Language：Japanese   Publisher：The Japanese Society of Clinical Pharmacology and Therapeutics  

DOI： 10.3999/jscpt.23.87

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

Scopus

PubMed

researchmap

Language：Japanese   Publisher：The Japanese Society of Clinical Pharmacology and Therapeutics  

DOI： 10.3999/jscpt.22.409

researchmap

Language：Japanese   Publisher：The Japanese Society of Clinical Pharmacology and Therapeutics  

DOI： 10.3999/jscpt.21.215

researchmap

Language：Japanese   Publisher：The Japanese Society of Clinical Pharmacology and Therapeutics  

DOI： 10.3999/jscpt.20.127

researchmap

Language：English   Publisher：(公社)日本実験動物学会  

肝臓の薬物代謝酵素シトクロムP450(CYP)の一部は性的二形性を示し、薬物の効果や副作用の性差の原因として臨床上重要な問題となっている。ラットにおいてCYPの性的二形性は下垂体成長ホルモン(GH)の分泌パターンの性差に強く依存するとされているが、詳細なメカニズムは明らかでない。我々は、以前にマウスアルブミンエンハンサー/プロモーターの制御下で、肝細胞特異的に蛍光タンパク質DsRed2遺伝子を発現するトランスジェニック(Alb-DsRed2 Tg)ラットを作製し、肝DsRed2発現が成熟雄ラットに限定される性的二形を示すことを報告した。本研究では、GH分泌パターンに依存する内因性CYP発現と性的二形性DsRed2発現の関連性を検討するために、本ラットのGH分泌パターンを雌雄で逆転させ、肝CYPおよびDsRed2発現を比較した。生後1日目に雌雄Alb-DsRed2 Tgラットの性腺を摘出し、雌には同時にテストステロンプロピオネートを投与した。従来の報告と一致して、実験的にGH分泌パターンを雌雄で逆転させるとCYPの性的二形性発現が逆転し、それと同期して本ラットのDsRed2発現の性的二形性が逆転した。肝DsRed2発現は性的二形CYP発現と強く相関し、本ラットはGH分泌パターンに依存する性的二形CYP発現の変化を簡便に評価できる有用なツールであることが明らかとなった。(著者抄録)

DOI： 10.1538/expanim.16-0030

researchmap

Language：Japanese   Publisher：(一社)日本未病システム学会  

researchmap

Language：Japanese   Publisher：日本アルコール・アディクション医学会  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER THORACIC SOC  

Web of Science

researchmap

Language：Japanese   Publisher：(公社)日本生化学会  

researchmap

Language：Japanese   Publisher：(NPO)日本法医学会  

researchmap

Language：Japanese   Publisher：(一社)日本未病システム学会  

researchmap

Language：Japanese   Publisher：(一社)日本糖尿病学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese   Publisher：(公社)日本生化学会  

J-GLOBAL

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：(一社)日本未病システム学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：English   Publisher：INT PRESS EDITING CENTRE INC  

Original WBN/Kob male rats commonly develop chronic pancreatitis by the age of 3 months, while diabetes mellitus occurs at 9 months. In contrast, female rats of this strain do not show pancreatitis or diabetes. The WBN/Kob-fatty rat is a homozygous (fa/fa) congenic strain for the fa allele of the leptin receptor gene (Lepr). In WBN/Kob-fatty rats, both females and males provide a model of non-insulin-dependent diabetes with obesity. The leptin receptor fatty gene (Lepr(fa)) induces obesity and hyperphagia. In the present study, we examined the effect of dietary restriction on pancreatitis and diabetes in female WBN/Kob-fatty rats. Five female fatty rats comprised a restricted feeding group with paired-feeding from 3 to 13 weeks of age, and five female lean rats comprised a control group with paired-feeding. At 13 weeks of age, two of the five female fatty rats of the control group developed diabetes mellitus, while no female fatty rats of the restricted feeding group developed diabetes mellitus. At this stage, pathological changes of the pancreas were observed in female fatty rats. All female fatty rats showed severe interlobular, intra-lobular and intra-islet fibrosis. In female fatty rats of the restricted feeding group, pathological changes of the pancreas were milder those of the free-feeding fatty group. Although dietary restriction could not completely prevent pancreatitis in female fatty rats, the development of diabetes was inhibited by its reduction of the severity of pancreatitis.

DOI： 10.1538/expanim.59.623

Web of Science

researchmap

Language：Japanese   Publisher：(公社)日本獣医学会  

researchmap

Language：Japanese   Publisher：(株)研成社  

researchmap

Language：Japanese   Publisher：(公社)日本獣医学会  

researchmap

Language：Japanese   Publisher：(公社)日本獣医学会  

researchmap

Language：Japanese   Publisher：(株)日本臨床社  

CiNii Books

researchmap

Other Link： http://search.jamas.or.jp/link/ui/2008225354

Language：Japanese   Publisher：(公社)日本獣医学会  

researchmap

Language：Japanese   Publisher：(株)メディカルレビュー社  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE BV  

Web of Science

researchmap

Language：Japanese   Publisher：(公社)日本獣医学会  

researchmap

Language：Japanese   Publisher：日本疾患モデル学会  

researchmap

Language：Japanese   Publisher：(株)メディカルレビュー社  

researchmap

Language：Japanese   Publisher：(一社)日本肝臓学会  

researchmap

Language：Japanese   Publisher：(公社)日本獣医学会  

researchmap

Language：English  

Aim: The aim of the present study was to compare the hemodynamic features of portal hypertension in rats with early cirrhosis with those of rats with advanced cirrhosis following common bile duct ligation (CBDL). Methods: A total of 53 male Sprague-Dawley rats were used. Hemodynamics were evaluated under conscious and unrestrained conditions 4 weeks and 8 weeks after CBDL. and 4 weeks after a sham operation. Arterial pressure and portal pressure were measured directly via catheters placed in the right femoral artery and main portal vein, respectively. The cardiac index and organ (splanchninc organs, brain, kidneys and lungs) blood flow were determined by the reference sample method using 141Ce-labeled microspheres (15 μm in diameter). Arterial levels of endothelin-1 and nitrate/nitrite, as well as liver function variables, were also determined. Results: Portal pressure was significantly higher 8 weeks after CBDL (15.8±2.1, n=8) than 4 weeks after CBDL (13.9±2.1 mmHg, n=12, p&lt
0.05), and the hyperdynamic circulation of the early period was attenuated (p&lt
0.05). Although hepatic artery blood flow 4 and 8 weeks after CBDL was higher than that after sham operation (p&lt
0.05), portal territory blood flow was not increased. There was a significant positive correlation between portal pressure and portal territory blood flow 8 weeks after CBDL (r=0.822, n=8, p=0.012). In rats with anemia 4 weeks after CBDL, the hemoglobin concentration was negatively correlated with portal territory blood flow (r= - 0.597, n=12, p=0.040). Conclusion: Portal pressure was higher 8 weeks after CBDL than 4 weeks after CBDL and increased with portal territory blood flow, suggesting that portal hypertension is maintained by a mechanism consistent with the forward flow theory. Anemia might exacerbate the hyperdynamic systemic circulation 4 weeks after CBDL.

DOI： 10.1272/jnms.72.217

Scopus

PubMed

researchmap

Language：English   Publisher：SPRINGER TOKYO  

Background: Rats with chronic bile duct ligation (CBDL) and portal vein ligation (PVL) are used as models of portal hypertension. CBDL rats show hypoxemia with intrapulmonary vasodilatation (IPVD), and are recognized as a model of hepatopulmonary syndrome (HPS), while PVL rats are normoxemic. We investigated the differences in arterial oxygenation between these models, and the key factors leading to HPS. Methods: Forty-eight Sprague-Dawley rats were prepared as CBDL or PVL models, or as Sham rats. Arterial oxygenation, hemodynamics (reference sample method), and IPVD were simultaneously evaluated in conscious and unrestrained animals, using Ce-141- or Sn-113-labeled microspheres (15 mu m in diameter), respectively. Endothelin-1 (ET-1) and nitrate/nitrite (end products of nitric oxide; NOx) production by the lung tissue (increment across the lungs) was also determined. Results: The extent of IPVD was similar in both models, but hypoxemia was only observed in CBDL rats. The ET-1 level and the increment in NOx were significantly increased in CBDL rats, and the increment was directly correlated with impairment of oxygenation. Blood flow through the bronchial arteries (anatomical shunting) was increased in CBDL rats, reaching more than three times the level in PVL rats or Sham rats. Conclusions: These results support the hypothesis that NO derived from the lung tissues contributes to hypoxemia, and IPVD appears to be a prerequisite for impaired oxygenation. The considerable increase of anatomical shunting may potentially contribute to impaired oxygenation in CBDL rats.

DOI： 10.1007/s00535-005-1633-9

Web of Science

researchmap

Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

researchmap

Language：English   Publisher：INT PRESS EDITING CENTRE INC  

The common bile duct-ligated (CBDL) rat, which is widely used as a model of human cirrhosis, rapidly develops secondary biliary cirrhosis (SBC) within 4 weeks. The CBDL rat shows poor viability, however, a detailed examination of the causes of its death has not been made. In this study, we investigated the outcome of bile duct ligation in detail and attempted to extend the life span of this model by feeding the animals a diet supplemented with nutrients. Survival rate, blood chemistry, blood cell counts, plasma levels of K vitamins and liver histology were compared among CBDL rats fed a standard diet and an enriched diet. Sham-operated rats were used as a control. Six out of 18 CBDL rats fed the standard diet died within 32 days of operation. The cause of death was massive internal hemorrhage in various organs or body cavities. All CBDL rats fed the enriched diet survived more than 31 days, but the viability of CBDL rats was not significant between those fed the standard diet and the enriched diet. The degree of anemia correlated significantly with the prolongation of prothrombin time. Plasma vitamin K1 levels in CBDL rats were significantly lower than those in sham-operated rats, but vitamin K2 levels were similar. We suggest that massive hemorrhage, which was the direct cause of death, is caused by the impairment of hemostasis resulting from vitamin K deficiency. The enriched diet with vitamin K nutritional supplements seemed to contribute to the prolongation of the life span of CBDL rats.

DOI： 10.1538/expanim.54.155

Web of Science

researchmap

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

researchmap

Language：Japanese   Publisher：(一財)日本消化器病学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：日本疾患モデル学会  

researchmap

Language：Japanese   Publisher：(株)メディカルレビュー社  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE BV  

Web of Science

researchmap

Language：Japanese   Publisher：(一財)日本消化器病学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：W B SAUNDERS CO  

DOI： 10.1016/S0168-8278(03)00430-6

Web of Science

researchmap

Language：Japanese   Publisher：(公社)日本獣医学会  

researchmap

Language：Japanese   Publisher：(一財)日本消化器病学会  

researchmap

Language：Japanese   Publisher：(株)メディカルレビュー社  

researchmap

Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

researchmap

Language：Japanese   Publisher：(一社)日本肝臓学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：W B SAUNDERS CO  

Web of Science

researchmap

Language：Japanese   Publisher：(公社)日本獣医学会  

researchmap

Language：Japanese   Publisher：(株)メディカルレビュー社  

researchmap

Language：Japanese   Publisher：(株)メディカルレビュー社  

researchmap

Language：English   Publisher：INT PRESS EDITING CENTRE INC  

A simple and useful method for the detection of C. kutscheri from the oral cavity of living rats was devised. In 10 sacrificed rats from two naturally and subclinically infected conventional colonies, 10(4.28) or 10(3.84) CFU/ml C. kutscheri were isolated from upper incisor swab extractions, while 10(1.38) or 10(1.58) and &lt;10 or 10(1.56) CFU/ml from the upper soft palate and pharynx, respectively. In another survey with 26 living animals, which were reared on the same rack, organisms were detected from the upper incisor and gingival swabs in 15 of 26 rats (57.7%). The results were reproducible at a second survey 10 days later. No organisms were isolated from any sites of the orally negative rats. These results indicated that culture of swab specimens from the upper incisors and gingivae of incisors is useful for the detection of C. kutscheri infection in living rats.

DOI： 10.1538/expanim.51.99

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：(一財)日本消化器病学会  

researchmap

Language：Japanese   Publisher：(公社)日本獣医学会  

researchmap

Language：English   Publisher：Japanese Society of Clinical Pharmacology and Therapeutics  

A new evaluation method for the treatment of chronic pancreatitis was devised using male WBN/Kob (WBN) rats as a human chronic pancreatitis model
in these rats, the lesion is spontaneously manifested at about 12 weeks of age. As a result of screening for drugs that inhibit the development of pancreatitic lesions in WBN rats, the inhibitory effects of estradiol (10 and 40 μg/kg, i. p., twice a week), camostat mesylate (100 mg/kg, p. o., daily) and allopurinol (100 mg/kg p. o., daily) were observed among estrogen, testosterone lowering agent, trypsin inhibitors and depressors of active oxygen. The efficacy of camostat mesylate and allopurinol which might be safely used for the treatment of progressive chronic pancreatitis were evaluated. Camostat mesylate was found to be effective, but not allopurinol. The expression of cells at the DNA synthesis stage as determined based on Brd Uridine (BrdU) uptake was examined. The uptake of BrdU notably occurred in acinar cells adjacent to the pancreatitic area. The regeneration of the pancreas as a result of the pancreatic trophic effect is the mechanism through which camostat mesylate is effective against lesions (mainly fibrosis) of chronic pancreatitis during the progression stage. One week after camostat mesylate administration, the weight of the pancreas increased rapidly, during which the uptake of BrdU in cells increased concurrently, indicating that regeneration of the pancreas occurred during this period. The most effective parameter for evaluating the efficacy of a drug for pancreatitis is the percentage of pancreatitic area employed in our histopathological study. We concluded that the use of WBN rats is pharmacologically effective for drug evaluation.

DOI： 10.3999/jscpt.32.5_231

Scopus

researchmap

Language：English   Publisher：Japanese Society of Clinical Pharmacology and Therapeutics  

A new evaluation method for the treatment of chronic pancreatitis was devised using male WBN/Kob (WBN) rats as a human chronic pancreatitis model
in these rats, the lesion is spontaneously manifested at about 12 weeks of age. As a result of screening for drugs that inhibit the development of pancreatitic lesions in WBN rats, the inhibitory effects of estradiol (10 and 40 μg/kg, i. p., twice a week), camostat mesylate (100 mg/kg, p. o., daily) and allopurinol (100 mg/kg p. o., daily) were observed among estrogen, testosterone lowering agent, trypsin inhibitors and depressors of active oxygen. The efficacy of camostat mesylate and allopurinol which might be safely used for the treatment of progressive chronic pancreatitis were evaluated. Camostat mesylate was found to be effective, but not allopurinol. The expression of cells at the DNA synthesis stage as determined based on Brd Uridine (BrdU) uptake was examined. The uptake of BrdU notably occurred in acinar cells adjacent to the pancreatitic area. The regeneration of the pancreas as a result of the pancreatic trophic effect is the mechanism through which camostat mesylate is effective against lesions (mainly fibrosis) of chronic pancreatitis during the progression stage. One week after camostat mesylate administration, the weight of the pancreas increased rapidly, during which the uptake of BrdU in cells increased concurrently, indicating that regeneration of the pancreas occurred during this period. The most effective parameter for evaluating the efficacy of a drug for pancreatitis is the percentage of pancreatitic area employed in our histopathological study. We concluded that the use of WBN rats is pharmacologically effective for drug evaluation.

DOI： 10.3999/jscpt.32.5_231

Scopus

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：日本臨床生理学会  

researchmap

Language：English   Publisher：INT PRESS EDITING CENTRE INC  

The rat dominant hairless gene (Ht) of the WBN/IIa-Ht rat causes atrichosis in Ht/Ht and hypotrichosis in Ht/+. Furthermore the Ht/Ht shows signs of abnormal keratinization and almost all of the Ht/Ht die in an immature stage before weaning in the conventional environment Ht/+ was affected by dermatitis caused by Staphylococcus aureus, suggesting that the gene Ht might involve defense mechanisms against infection. In this study, we performed the linkage analysis of the gene Ht by outocross with the Brown Norway rat in the SPF environment Ninety-six backcross progeny of (BN x WBN/IIa-Ht/Ht) F1 x WBN/IIa- Ht/Ht were typed with microsatellite markers and the gene Ht was mapped on chromosome 10 between Asgr1 and Nos2 within the map distance of 6.2 cM.

DOI： 10.1538/expanim.49.137

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：(公社)日本獣医学会  

researchmap

Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：JAPAN EXPER ANIMAL RES ASSN  

Deodorizing effect of ozone was investigated comparing two types of compact ozonizing apparatus made on an experimental basis. The concentrations of ammonia and trimethylamine were examined as an indicator for deodorizing effect of ozone in animal rooms of rats and guinea pigs at laboratory animal facilities of three different universities. Both of the ozonizing apparatus were able to remove ammonia and trimethylamine in animal rooms, with no significant difference in the performance of the two apparatus.

DOI： 10.1538/expanim.44.255

Web of Science

researchmap

Language：Japanese   Publisher：医学図書出版(株)  

WBN/Kob雄ラットの自然発症膵炎に対するFUT-187経口投与の効果を膵病理組織学的検索により検討した. 1)WBN/Kobラットの膵病変に対するFUT-187の予防的投与により,明白な膵実質萎縮および膵組織変性の抑制が確認された. 2)予防的投与後10週間の休薬実験において,FUT-187の持続的膵炎抑止効果が窺われたが,休薬により膵組織障害は進行することが明らかにされた. 3)FUT-187の治療的投与により,膵病変の改変が確認され,障害膵に対して,その修復再生を惹起する作用のあることが示唆された

researchmap

Language：English   Publisher：AMER ASSOC LABORATORY ANIMAL SCIENCE  

Distribution of Corynebacterium kutscheri was determined in 41 rats housed in a conventionally managed colony that were infected naturally and subclinically. At 2, 5, 10, 20 and 25 months after initial isolation of C. kutscheri, attempts were made to isolate C. kutscheri from 17 sites, with a new selective medium, FNC agar. In total, the prevalence (97.6%) of C. kutscheri isolation was significantly (P &lt; 0.001) higher than the frequency (70.7%) of antibody detection None of the rats manifested any distinct clinical signs of disease and macroscopic lesions caused by C. kutscheri were not detected. In 40 rats with subclinical infection, the organisms were most frequently isolated from the oral cavity, esophagus, cecal contents, and colon and rectum (&gt;95.0%). The isolation rate was next highest in the trachea, submaxillary lymph nodes, and nasal cavity (47.5 to 52.5%). The organisms hardly colonized the lung, liver, and kidney. Mean numbers of organisms found in the esophagus, cecal contents, and colon and rectum ranged from 10(3.9) to 10(4.2) CFU/g, and were significantly (P &lt; 0.05, P &lt; 0.01) high in comparison with those in the lung. These results indicated that many healthy rats in the naturally infected colony harbored C. kutscheri, and the organisms colonized the oral cavity, esophagus, cecal contents, and colon and rectum most frequently.

Web of Science

researchmap

researchmap

researchmap

researchmap

researchmap

Language：Japanese   Publisher：(公社)日本実験動物学会  

Gross morphology of the pancreas and distribution of pancreatic ducts were investigated in 12 Jcl: Wistar rats. The pancreas consisted of a body and two (right and left) lobes. The pancreatic body was located along the cranial part of the duodenum. The right lobe extended into the duodenal ligament, while the left lobe extended toward the spleen into the gastrolienal ligament. In 9 animals, the number of ducts ranged between 3 and 10. Each duct joined the hepatoenteric duct. Two (right and left) large ducts found in all animals drained the right and left lobes. Other ducts observed in more than a half of the animals drained either the body or a part of the lobe.

DOI： 10.1538/expanim1978.43.2_257

researchmap

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：JAPAN EXPER ANIMAL RES ASSN  

Gross morphology of th@ pancreas and distribution of pancreatic ducts were investigated in 12 Jcl : Wistar rats. The pancreas consisted of a body and two (right and left) lobes. The pancreatic body was located along the cranial part of the duodenum. The right lobe extended into the duodenal ligament, while the left lobe extended toward the spleen into the gastrolienal ligament. In 9 animals, the number of ducts ranged between 3 and 10. Each duct joined the hepatoenteric duct. Two (right and left) large ducts found in all animals drained the right and left lobes. Other ducts observed in more than a half of the animals drained either the body or a part of the lobe.

DOI： 10.1538/expanim1978.43.2_257

Web of Science

researchmap

Language：Japanese   Publisher：(公社)日本実験動物学会  

The hereditary hypotrichotic (WBN/Ila-Ht) rat is affected by dermatitis characterized by erosions and crust formation on dorsal skin areas. The bacterial flora of this dermatitis and the normal skin of the hypotrichotic rat was examined. As controls the cutaueous flora of atrichotic and Wistar rats was examined, and the results compared with those in hypotrichotic rats. The total number of bacterial colonies from the lesions and normal skin of hypotrichotic rats were 3.9&times;10⁵ to 1.16&times;10⁸ CFU/cm² and 1.6&times;10³ to 1.8&times;10⁴CFU/cm², respectively. In the lesions, overwhelming numbers of S. aureus were detected as almost pure cultures. In the normal skin, S. aureus was predominant, accounting for about 90% of all bacteria. The total number of bacterial colonies in the atrichotic rats was the same as in the hypotrichotic rats. The majority of the isolates were Staphylococcus sp., and about half of them were identified as S. aureus. The total number of bacterial colonies from the skin of individual Wistar rats varied extremely, ranging from 64 to 2.98&times;10⁵ CFU/cm². The flora mainly consisted of coagulase-negative Staphylococcus (CNS), S. aureus, and &alpha;-hemolytic Streptococcus sp., and CNS was isolated most frequently. Histopathological examination of the eroded portions in hypotrichotic rats revealed many clusters of coccoid bacteria and neutrophilic cell infiltration of the epidermis. These findings suggest that the dermatitis in hypotrichotic rats was caused by S. aureus and affected by unknown traits of these rats.

DOI： 10.1538/expanim1978.43.1_85

researchmap

Publisher：Japanese Association for Laboratory Animal Science  

The hereditary hypotrichotic (WBN/Ila-Ht) rat is affected by dermatitis characterized by erosions and crust formation on dorsal skin areas. The bacterial flora of this dermatitis and the normal skin of the hypotrichotic rat was examined. As controls the cutaueous flora of atrichotic and Wistar rats was examined, and the results compared with those in hypotrichotic rats. The total number of bacterial colonies from the lesions and normal skin of hypotrichotic rats were 3.9&times;10⁵ to 1.16&times;10⁸ CFU/cm² and 1.6&times;10³ to 1.8&times;10⁴CFU/cm², respectively. In the lesions, overwhelming numbers of S. aureus were detected as almost pure cultures. In the normal skin, S. aureus was predominant, accounting for about 90% of all bacteria. The total number of bacterial colonies in the atrichotic rats was the same as in the hypotrichotic rats. The majority of the isolates were Staphylococcus sp., and about half of them were identified as S. aureus. The total number of bacterial colonies from the skin of individual Wistar rats varied extremely, ranging from 64 to 2.98&times;10⁵ CFU/cm². The flora mainly consisted of coagulase-negative Staphylococcus (CNS), S. aureus, and &alpha;-hemolytic Streptococcus sp., and CNS was isolated most frequently. Histopathological examination of the eroded portions in hypotrichotic rats revealed many clusters of coccoid bacteria and neutrophilic cell infiltration of the epidermis. These findings suggest that the dermatitis in hypotrichotic rats was caused by S. aureus and affected by unknown traits of these rats.

DOI： 10.1538/expanim1978.43.1_85

researchmap

researchmap

researchmap

Language：English   Publisher：AMER ASSOC LABORATORY ANIMAL SCIENCE  

Corynebacterium kutscheri was isolated from the oral cavities of 12 males Syrian hamsters (Mesocricetus auratus) which were about 12 months old. At 1, 5, and 9 months after initial isolation of C. kutscheri from the oral cavity, hamsters were euthanatized, and attempts were made to culture C. kutscheri from 13 additional sites. Corynebacterium kutscheri was isolated from nine hamsters, and regardless of the hamsters' ages, the organisms were most frequently isolated from the oral cavity (100%), esophagus (100%), cecal content (100%), and colon and rectum (88.9%). Isolation rates in the nasal cavity were 66.7%, followed by 55.5% in the trachea and 33.3% in the submaxillary lymph nodes. The number of the organisms found in the submaxillary lymph nodes and esophagus was 10(3) to 10(4) CFU/g. The number found in the cecal content and in the colon and rectum was 10(2) to 10(5) CFU/g. The organisms were not isolated from lung, stomach, kidney, spleen, and mesenteric lymph node tissues. The hamsters had neither clinical signs nor lesions. However, 7 of 12 animals had low agglutinating antibody titers. The Syrian hamster can therefore be an asymptomatic carrier of C. kutscheri.

Web of Science

researchmap

Language：Japanese   Publisher：日本疾患モデル学会  

researchmap

Language：English   Publisher：HUMANA PRESS INC  

Web of Science

researchmap

Language：Japanese   Publisher：医学図書出版(株)  

WBN/Kob雄ラットに起こる自発性膵炎に対するウリナスタチン投与の効果を検討した.ウリナスタチン20,000 U/0.5 mlを病変発現初期の8週齢から12週齢の4週間,1日1回腹腔内に投与し,投与終了時に剖検して無処置群と対比させた.また,12週齢投与終了3ヵ月間無処置のまま経過させ,24週齢で無処置群ともに剖検し,膵組織を光顕微的に検索した.12週齢の検索では,全般的に比較的軽度な病変所見であったが,無処置群の膵小葉に局所的な著しい炎症所見がみられ,この様な所見は投与群では観察されなかった.24週齢検索では,無処置群の膵病変は腺房間質の浮腫,細胞浸潤,線維増生など著しいび漫性症像を呈していたのに対し,休薬群では膵管・血管を中心とした限局した部位における線維増生を主体とする局所性炎症所見であった

researchmap

researchmap

researchmap

Publisher：Japanese Association for Laboratory Animal Science  

DOI： 10.1538/expanim1985.5.79

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Language：English   Publisher：The Medical Association of Nippon Medical School  

DOI： 10.1272/jnms1923.54.681

researchmap