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Y Ohkubo

Publications and source records attributed to Y Ohkubo.

At least 37 records · Page 2Linked to original sources
PubMed2001

Activation of mu-opioid pathway is associated with the canceling effect of footshock stimulus on the restraint stress-induced inhibition of small intestinal motility in rats.

We previously reported that small intestinal motility was significantly inhibited by restraint stress, but not by footshock stress. In the present study, we found that plasma beta-endorphin levels were more significantly elevated by footshock stress than restraint stress, and that preloading of footshock stimulus canceled the inhibition of small intestinal motility by restraint stress. Pretreatment with the mu-opioid receptor antagonist naltrexone significantly attenuated this canceling effect of footshock stimulus. These results suggest that footshock stimulus may cancel the inhibition of small intestinal motility by restraint stress via activation of mu-opioid receptors.

Animals↗
PubMed2001

Transferrin is not involved in the entry of 67Ga into hepatocytes from regenerating liver of partially hepatectomized rats.

Ever since the first observation of 67Ga accumulation in tumors and inflammatory lesions, 67Ga has been used to detect various tumors and inflammations. The aims of this study were to clarify whether or not transferrin is involved in the uptake of 67Ga by the regenerating liver after partial hepatectomy. The uptake of 67Ga by the liver of rats reached a maximum 2 d after partial hepatectomy. In order to inhibit the binding of 67Ga to transferrin in the blood, FeCl3 was administered 5 min before the injection of 67Ga. The administration of FeCl3 decreased the uptake of 67Ga by the liver of the partially hepatectomized rats, suggesting that transferrin is involved in the uptake by the liver. However, 67Ga was taken up only slightly by hepatocytes obtained from the liver of these rats. We conclude that transferrin is involved in the uptake of 67Ga by the liver tissue of partially hepatectomized rats but is not involved in its entry into the hepatocytes. Only a slight amount of gallium-67 enters the hepatocytes, and may accumulate primarily in the extracellular matrix of the liver tissue of these rats.

Animals↗
PubMed2001

Evaluation of the effects of restraint and footshock stress on small intestinal motility by an improved method using a radionuclide, 51Cr, in the rat.

The effect of two different stress stimuli, restraint stress and footshock stress, on small intestinal motility was evaluated by a more reliable method with improvement of the previous method using a radionuclide, 51Cr. The small intestinal transit was significantly inhibited by restraint stress, but not by footshock stress, although plasma corticosterone levels were significantly elevated to the same extent by restraint stress and footshock stress. These results suggest that restraint stress and footshock stress stimuli influence small intestinal motility via different mechanisms, but the reason for the difference is unclear. This experimental system using 51Cr seems to be useful for the elucidation of mechanisms for restraint stress-induced dysfunction of small intestinal motility because of its excellent quantitative evaluation of small intestinal transit.

Animals↗
PubMed2001

Beta3-adrenoceptor is involved in the inhibition of small intestinal motility due to restraint stress in rats.

We have reported that acute restraint stress inhibits small intestinal motility in rats. In order to clarify this inhibitory mechanism, we examined the effects of alpha- and beta-adrenergic antagonists on the inhibition of small intestinal motility induced by restraint stress. This inhibition underwent recovery by propranolol (beta1/beta2-antagonist) or SR59230A (beta3-antagonist), but not by atenolol (beta1-antagonist), ICI-118,551 (beta2-antagonist), prazosin (alpha1-antagonist) or yohimbine (alpha2-antagonist). These results suggest that beta3-adrenoceptors play an important role in the inhibition of small intestinal motility caused by restraint stress.

Adrenergic alpha-Antagonists↗
PubMed2001

The anti-inflammatory effect of FR188582, a highly selective inhibitor of cyclooxygenase-2, with an ulcerogenic sparing effect in rats.

The anti-inflammatory and ulcerogenic effects of FR188582, 3-chloro-5-[4-(methylsulfonyl) phenyl]-1-phenyl-1H-pyrazole, were investigated. In a recombinant human cyclooxygenase (COX) enzyme activity, FR188582 inhibited COX-2 with an IC50 value of 0.017 microM, and the inhibition of prostaglandin (PG) E2 formation by FR188582 was over 6000 times more selective for COX-2 than COX-1. Oral administration of FR188582 dose-dependently inhibited adjuvant arthritis. This effect was threefold more potent than that of indomethacin. FR188582 and indomethacin dose-dependently suppressed the formation of immunoreactive PGE2, but not immunoreactive leukotriene (LT) B4, in arthritic paw. Unlike indomethacin, FR188582 did not induce visible gastric lesions in rats at doses up to 32 mg/kg, p.o. Furthermore, FR188582 did not inhibit the level of immunoreactive PGE2 and immunoreactive 6-keto PGF1alpha in rat gastric mucosa. These results suggest that FR188582, a highly selective COX-2 inhibitor, has a potent anti-inflammatory effect mediated by inhibition of PGE2 in inflamed tissues. The safety profile of FR188582 appears to be improved over the safety profile of indomethacin.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

[Two cases of pulmonary disease with perinuclear anti-neutrophil cytoplasmic antibody].

We encountered two cases of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA). The first was a case of idiopathic interstitial pneumonia diagnosed in a 73-year-old man since 1998. He was admitted to our hospital because of renal failure and anemia. The serum level of p-ANCA on admission was 264 EU, and specimens obtained by percutaneous renal biopsy showed crescentic glomerulonephritis and vasculitis due to p-ANCA. He was treated with prednisolone pulse therapy and prednisolone (PSL), however interstitial pneumonia occurred during PSL tapering. We treated him for pulmonary fibrosis with plasmapheresis, methylprednisolone (mPSL) and cyclophosphamide (CPA), which suppressed the progress of the interstitial pneumonia. The second case was one of massive pulmonary hemorrhage in a 68-year-old man who was admitted to our hospital. Physical examination revealed anemia: the laboratory data, renal failure; and the serum level of p-ANCA was elevated to 611 EU. The specimens obtained by percutaneous renal biopsy showed crescentic glomerulonephritis and vasculitis. The renal failure was not improved by PSL, but, together with the inflammation, responded to the combination of PSL and CPA. However, both patients died of serious infection. They were regarded as compromised patients because of the therapy mentioned above. No standard therapy has been established against p-ANCA positive pulmonary disease with renal failure. The treatment should control the progression of interstitial pneumonitis and pulmonary hemorrhage. It is important to consider the possibility of serious infection.

Aged↗
PubMed2001

[A case of renal cell carcinoma complicated with interstitial pneumonitis, complete A-V block and pleural effusion during interferon-alpha therapy].

A 76-year-old man with postoperative renal cell carcinoma accompanied by multiple lung metastasis was being treated with recombinant interferon-alpha. After administration of 3 MU/day on 3 days/week for 1 month, he complained of headache and tinnitus. During continuous treatment for 3 months, he complained of appetite loss, low-grade fever and dyspnea. He was then referred to our Department of Internal Medicine. Electrocardiography indicated a complete A-V block, and chest radiography (CXR) showed a reticular shadow in both lower lung fields and bilateral pleural effusion. Chest computed tomography (CT) indicated subpleural emphysematous changes, multiple nodules, consolidation shadow with ground glass opacity in both lower lobes, and bilateral pleural effusion. The findings in the bronchoalveolar lavage (BAL) fluid included increases in the numbers of lymphocytes and eosinophils. We reached a diagnosis of interferon-alpha-induced pneumonitis on the basis of the patient's clinical course, and the CXR, chest CT and BAL fluid findings. Treatment with methylprednisolone pulse therapy for 3 days and then administration of prednisolone for 1 month resulted in marked improvement in the complete A-V block and interstitial pneumonitis. At day 7 after discontinuation of prednisolone, the serum level of C-reactive protein increased, and CXR showed bilateral pleural effusion. We therefore believe that the pleural effusion was probably also induced by interferon-alpha. Interferon is an effective drug for chronic hepatitis C and malignant diseases. Many complications have been reported during interferon therapy. However, although these complications, such as interstitial pneumonitis, complete A-V block and pleural effusion, have rarely been reported, careful attention is required during interferon therapy in case any appear.

Aged↗
PubMed2000

Cost-effectiveness of intensive insulin therapy for type 2 diabetes: a 10-year follow-up of the Kumamoto study.

To evaluate the cost and effectiveness of intensive insulin therapy for type 2 diabetes on the prevention of diabetes complications in Japan, we performed economic evaluation based on a randomized controlled trial. A total of 110 patients with type 2 diabetes were randomly assigned into two groups, a multiple insulin injection therapy (MIT) group or a conventional insulin injection therapy (CIT) group, and were followed-up for 10 years. Economic evaluation (cost-consequences analysis) was applied to evaluate both health and economic outcomes. As outcome measures for effectiveness of intensive insulin therapy, the frequency of complications, such as retinopathy, nephropathy, neuropathy, macrovascular event, and diabetes-related death, was used. For estimating costs, a viewpoint of the payer (the National Health Insurance) was adopted. Direct medical costs associated with diabetes care during 10 years were calculated and evaluated. In a base case analysis, all costs were discounted to the present value at an annual rate of 3%. Sensitivity analyses were carried out to assess the robustness of the results to changes in the values of important variables. MIT reduced the relative risk in the progression of retinopathy by 67%, photocoagulation by 77%, progression of nephropathy by 66%, albuminuria by 100% and clinical neuropathy by 64%, relative to CIT. Moreover, MIT prolonged the period in which patients were free of complications, including 2.0 years for progression of retinopathy (P<0.0001), 0.3 years for photocoagulation (P<0.05), 1.5 years for progression of nephropathy (P<0.01) and 2.2 years for clinical neuropathy (P<0.0001). The total cost (discounted at 3%) per patient during the 10-year period for each group was $30310 and 31525, respectively. The reduction of total costs in MIT over CIT was mainly due to reduced costs for management of diabetic complications. Our results show that MIT is more beneficial than CIT in both cost and effectiveness. Therefore, MIT is recommended for the treatment of type 2 diabetic patients who require insulin therapy as early as possible from the perspective of both patients and health policy.

Adult↗
PubMed2000

FK506 inhibition of histamine release and cytokine production by mast cells and basophils.

Histamine release and cytokine production by mast cells and basophils are thought to be closely involved in the pathogenesis of allergic diseases. Some reports show that FK506 (tacrolimus hydrate) inhibited histamine release and cytokine production by mast cells and basophils. However, as the effects of FK506 has not been compared with those of clinically used drugs in those reports, the clinical relevancy of FK506 inhibition remained unclear. In this paper, we compared the actions of FK506 with those of steroids or disodium cromoglycate (DSCG) which has been clinically used. FK506 inhibited histamine release by Brown-Norway rat peritoneal mast cells more potently than steroids and especially DSCG. FK506 also inhibited histamine release by a mast rat basophilic leukemia (RBL)-1 cell line and human peripheral blood basophils, whereas steroids failed to inhibit histamine release by human basophils. FK506 as well as steroids inhibited TNF-alpha and IL-4 production by RBL-1 cells. FK506 was therefore more effective than steroids and DSCG in inhibiting histamine release, and it also had the ability of inhibiting cytokine production by mast cells as steroids do. We concluded that FK506 might regulate allergic diseases via these actions, judging from the viewpoint of clinical relevancy.

Animals↗
PubMed2000

Acute disseminated encephalomyelitis after live rubella vaccination.

We report here a case involving a 14-year-old boy who developed acute disseminated encephalomyelitis following live rubella vaccination. The patient became febrile and began to experience nuchal pain 16 days after the immunization. By 22 days after immunization, he experienced difficulty in walking. By 24 days, he had developed tetraparesis with retention of urine, and total sensory loss below the Th1 dermatomal level. He was febrile at this point and showed nuchal rigidity and Lhermitte's sign. Cerebrospinal fluid examination revealed elevated cell counts, protein level, and myelin basic protein. T2-weighted magnetic resonance imaging detected high intensity lesions in the bilateral cerebral white matter and cervical spinal cord. Following the administration of intravenous corticosteroids, the patient's clinical symptoms improved rapidly.

Adolescent↗
PubMed2000

FK506 potently inhibits T cell activation induced TNF-alpha and IL-1beta production in vitro by human peripheral blood mononuclear cells.

The aim of this study was to elucidate the in vitro inhibitory potency of FK506 on production of the inflammatory cytokines, tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta, with a view to assessing this immunosuppressive agent as a potential anti-rheumatic drug. We employed an in vitro model which produces TNF-alpha and IL-1beta through T cell activation. Human peripheral blood mononuclear cells (PBMC) were cultured with immobilized anti-CD3/CD28 monoclonal antibody in this model. FK506 inhibited anti-CD3/CD28 induced TNF-alpha and IL-1beta production at concentrations less than 1 ng ml(-1). Flow cytometric analysis of intracellular TNF-alpha and IL-1beta positive cells showed that FK506 potently suppresses inflammatory cytokine production from CD14+ monocytes as well as from T cells. Cyclosporin A (CsA) and dexamethasone (DEX) also inhibited the anti-CD3/CD28 induced cytokine production, but were less potent than FK506. FK506 and CsA, but not DEX, specifically inhibited anti-CD3/CD28 induced inflammatory cytokine production without affecting the lipopolysaccaride (LPS) induced effect. Methotrexate (MTX) was completely inactive for suppressing cytokine production under either condition. Anti-CD3/CD28 stimulated PBMC culture supernatants were found to enhance the expression of adhesion molecules in human vascular endothelial cells. FK506, CsA and DEX led to the suppression of adhesion molecule expression probably by inhibiting cytokine production from PBMC. The inhibitory potency of agents on TNF-alpha and IL-1beta production was compared with cytotoxicity and FK506 was not cytotoxic at concentrations several orders of magnitude greater than those required for cytokine inhibition. These results strongly suggest that FK506 may be most effective to specifically prevent T cell activation mediated inflammatory cytokine production in a clinical setting.

Antibodies↗
PubMed2000

Development of an experimental system for evaluation of the effect of stress on intestinal motility using a radionuclide, 51Cr, in the rat.

We attempted to develop an experimental system for evaluation of the influence of stress on small intestinal motility using a radionuclide, 51Cr, and an acute restraint stress model. Each rat was immobilized in an adjustable restraint device for 1 to 5 h. The rat was given 51Cr immediately after the end of stress loading through a catheter inserted into the duodenum, and sacrificed 20 min after administration. The small intestine was removed and the 51Cr radioactivity was continuously monitored with an NaI-scintillation survey meter. The small intestinal motility was estimated by the distance of the radioactive peak from the top of the duodenum. The small intestinal motility was significantly inhibited by 3 h-restraint stress. This experimental system is easy, rapid, and simple for the evaluation of the effect of stress on small intestinal motility.

Animals↗
PubMed2000

Involvement of transglutaminase in the receptor-mediated endocytosis of mouse peritoneal macrophages.

We investigated the effect of extracellular Ca2+ on the uptake of immunoglobulin G (IgG)-coated normal sheep red blood cells (SRBC) by the mouse peritoneal macrophages. The uptake of SRBC was dose dependently enhanced by Ca2+ concentration. We also investigated the effect of ryanodine on the uptake of SRBC. Ryanodine showed approximately 15% inhibition of the uptake. The activity of transglutaminase (TGase) in the cytosolic fraction of macrophages was enhanced as the Ca2+ concentration increased. The uptake of SRBC decreased by the addition of histamine, a TGase inhibitor. These results suggest that TGase is involved in the receptor-mediated endocytosis system of mouse peritoneal macrophages.

Animals↗
PubMed2000

Long-term results of the Kumamoto Study on optimal diabetes control in type 2 diabetic patients.

OBJECTIVE: To examine whether intensive glycemic control could decrease the frequency or severity of diabetic microvascular complications, an 8-year prospective study of Japanese patients with type 2 diabetes was performed. RESEARCH DESIGN AND METHODS: A total of 110 patients with type 2 diabetes (55 with no retinopathy [the primary prevention cohort] and 55 with simple retinopathy [the secondary intervention cohort]) were randomly assigned to multiple insulin injection therapy (MIT) groups and administered three or more daily insulin injections or assigned to conventional insulin injection therapy (CIT) groups and administered one or two daily intermediate-acting insulin injections. Worsening of microvascular complications was regularly assessed during 8 years. Two or more steps up in the 19 stages of the modified Early Treatment of Diabetic Retinopathy Study classification in retinopathy and one or more stages up among three stages in nephropathy (normoalbuminuria, microalbuminuria, and albuminuria) were defined as worsening of complications. RESULTS: In both primary prevention and secondary intervention cohorts, the cumulative percentages of worsening in retinopathy and nephropathy were significantly lower (P < 0.05) in the MIT group than in the CIT group. In neurological tests after 8 years, the MIT group showed significant improvement (P < 0.05) in the median nerve conduction velocities (motor and sensory nerves), whereas the CIT group showed significant deterioration (P < 0.05) in the nerve conduction velocities and vibration threshold. From this study, the glycemic threshold to prevent the onset and progression of diabetic microvascular complications was as follows: HbA1c < 6.5%, fasting blood glucose concentration < 110 mg/dl, and 2-h postprandial blood glucose concentration < 180 mg/dl. CONCLUSIONS: Intensive glycemic control can delay the onset and progression of the early stages of diabetic microvascular complications in Japanese patients with type 2 diabetes.

Adult↗
PubMed2000

[Measurement of the square measure of the pharynx and the positional diagnosis of airway obstruction during obstructive sleep apnea syndrome by dynamic MRI].

The purpose of this study was to apply dynamic MRI for the positional diagnosis of airway obstruction during snoring and sleep apnea and to compare the apnea hypopnea index (AHI) and the square measure of the pharynx obtained before and after laser-assisted uvula-palate-pharyngoplasty (LAUP). From December 1997 to October 1998, dynamic MRI and overnight monitoring were performed at the hospital of Tokyo Medical University on 42 patients who complained of snoring and symptoms related to sleep apnea syndrome (SAS). Of the 42 patients, four exhibited collapse at the position of the soft palate (soft palate type) as diagnosed by dynamic MRI, and four exhibited collapse at the position of the soft palate as well as the tongue (complex type). LAUP was performed on these eight patients with obstructive SAS (OSAS). After LAUP, the AHI of these eight patients with OSAS decreased significantly (p < 0.05). The square measure of the pharynx of these eight patients was increased (p < 0.01). The AHI of all four patients with soft-palate obstruction decreased, and the square measure of the pharynx of three of these four patients increased. The AHI of three of four patients with the complex type decreased, while the square measure of the pharynx of two of these four patients increased.

Adult↗
PubMed2000

[A case of limited Wegener granulomatosis with hypereosinophilia].

A 51-year-old female was admitted to Nagano Matsushiro General Hospital because of fever, cough and dyspnea on exertion. Her laboratory data revealed leukocytosis with hypereosinophilia, a high erythrocyte sedimentation rate and c-reactive protein. Chest radiography revealed an infiltration shadow with a cavity in the right upper lobe. A lung abscess was diagnosed and antibiotics were administered. Laboratory results showed improvement, but chest radiography continued to show cavities. She was admitted to our hospital because of fever, left pleural effusion and progression of cavities on chest radiographs. She showed no abnormalities of the upper airway or kidney, and was negative for c-antineutrophil cytoplasmic antibody (c-ANCA). Because a positive c-ANCA was seen on day 8 of hospitalization, L-type limited Wegener granulomatosis (WG) was diagnosed according to Gross et al. Prednisolone (PSL) was administered, which improved the anemia, eosinophilia and the cavities. On day 7 of PSL administration, of the left pneumothorax occurred as a complication caused by perforation of the left chest cavity, but her clinical course was good after a cavernectomy was performed. Some studies have reported that limited WG shows a negative c-ANCA, and that antibiotic therapy improves inflammation. The L-type of limited WG revealed a low-grade positive ratio and titer of c-ANCA. Moreover, L-type limited WG responds well to therapy. We therefore selected PSL administration only against L-type limited WG. We have reported L-type limited WG with eosinophilia and the negative effects of c-ANCA at an early clinical stage.

Antibodies, Antineutrophil Cytoplasmic↗