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Biomedical subjects

Junichi Yoshida

Publications and source records attributed to Junichi Yoshida.

26 records · Page 2Linked to original sources
PubMed2003

Angiotensin II type 1 and endothelin type A receptor antagonists modulate the extracellular matrix regulatory system differently in diastolic heart failure.

OBJECTIVE: Ventricular fibrosis plays a pivotal role in the development of diastolic heart failure and is a therapeutic target; however, the effects of pharmacological interventions on the extracellular matrix (ECM) regulatory system in diastolic heart failure remain to be clarified. DESIGN AND METHODS: Dahl salt-sensitive rats fed on a diet containing 8% NaCl from age 7 weeks--a hypertensive diastolic heart failure model--were divided into untreated rats, rats treated with angiotensin II type 1 (AT1) receptor antagonist and those treated with endothelin type A (ETA) receptor antagonist. RESULTS: Ventricular fibrosis progressed in the untreated rats, with increases in mRNA levels of type I collagen, matrix metalloproteinase-2, -9 and -13, and tissue inhibitor of metalloproteinase-1 and -2. Both antagonists attenuated ventricular fibrosis to the same degree. AT1 receptor blockade decreased the type I collagen mRNA level more than ETA receptor blockade. ETA receptor blockade did not decrease the matrix metalloproteinase-2 mRNA level that was decreased by AT1 receptor blockade, and decreased the tissue inhibitor of metalloproteinase-2 mRNA level that was not affected by AT1 receptor blockade. These led to a higher ratio of matrix metalloproteinase-2 to tissue inhibitor of metalloproteinase-2 mRNA levels and a greater 72-kDa gelatinase activity in the rats treated with ETA receptor antagonist than in those treated with AT1 receptor antagonist, and may well cancel out the lesser decline in collagen synthesis, resulting in the equivalent attenuation of ventricular fibrosis. CONCLUSIONS: AT1 receptor and ETA receptor antagonists provide their beneficial effects on the ECM through different modulation of its regulatory system.

Angiotensin Receptor Antagonists↗
PubMed2003

Angiotensin II type 1 receptor blockade prevents diastolic heart failure through modulation of Ca(2+) regulatory proteins and extracellular matrix.

BACKGROUND: Angiotensin II type 1 receptor (AT(1)R) blockade attenuates left ventricular relaxation abnormality and myocardial stiffening in a model of hypertensive diastolic heart failure, but the mechanisms remain unclear. OBJECTIVE: To test the hypothesis that such benefits are provided by modulation of the quantitative or qualitative changes, or both, in Ca2+ regulatory proteins and extracellular matrix. DESIGN AND METHODS: Dahl salt-sensitive rats fed a diet containing 8% sodium chloride from 7 weeks of age present pulmonary congestion as a result of diastolic dysfunction with preserved systolic function, around 20 weeks of age. In this study, animals of this model were divided into groups that received (n = 7) or did not receive (n = 6) a subdepressor dose of an AT(1)R antagonist (candesartan cilexetil) from 8 weeks of age. RESULTS: Long-term AT(1)R blockade prevented the development of diastolic heart failure through attenuation of left ventricular relaxation abnormality and myocardial stiffening without a reduction in blood pressure. Left ventricular relaxation abnormality was not associated with any change in the ratio of abundance of phospholamban to that of sarcoplasmic reticulum Ca2+-ATPase 2a protein, but was accompanied by a decrease in Ser16-phosphorylated phospholamban. The AT(1)R blockade inhibited this decrease. Attenuation in myocardial stiffening was associated with reduced tissue collagen content, attenuated collagen cross-linking, and suppressed gene expression of collagen type I rather than type III. CONCLUSIONS: AT(1)R blockade prevented abnormal relaxation at least partly through functional alterations in Ca2+-handling proteins in a hypertensive model of diastolic heart failure. It attenuated myocardial stiffening through preventing a shift in the phenotype of collagen synthesized and the accumulation of cross-linked collagen. These beneficial effects of AT(1)R blockade in diastolic heart failure are achieved without a reduction in blood pressure.

Angiotensin Receptor Antagonists↗
PubMed2003

[Influence of a long-term load of dietary cholesterol on the rat kidney].

The involvement of hyperlipidemia in aggravation of nephrosis has remained controversial. In this study, to examine the influence of cholesterol on the kidney, normal SD rats were loaded with a normal diet(4.4% fat, 0.09% cholesterol) plus 0.25% cholesterol for 10 months, and the urinary excretion of protein, blood cholesterol level and histological renal changes were compared with those in the control group given the normal diet alone. The urinary protein excretion was increased after 4 months of cholesterol loading and was about 6 times the control value at the end of the study(10 months). At 10 months, the blood levels of total, HDL- and LDL + VLDL-cholesterols were also increased, and the arteriosclerosis index(HDL/LDL + VLDL ratio) was about 1.3 times the control value. Histologically, segmental lesions of glomeruli containing sclerosis/PAS positive material were stronger than in the control animals. Thus, this study revealed increased blood cholesterol and urinary protein excretion and aggravated histological changes of the kidney in rats given a long-term cholesterol load, suggesting that cholesterol may be a risk factor affecting the kidney.

Animals↗
PubMed2002

Collaborative validation study of the in vivo micronucleus test using mouse colonic epithelial cells.

The in vivo micronucleus test using mouse colonic epithelial cells was evaluated as the 11th collaborative study organized by the Collaborative Study Group on the micronucleus test (CSGMT) with three model chemicals that were known to induce chromosome damage in mouse colonic cells. Five laboratories participated in this validation study. All three model chemicals, i.e. 1,2-dimethylhydrazine dihydrochloride (1,2-DMH), N-methyl-N-nitrosourea (MNU), and mitomycin C (MMC), induced micronucleated colonic epithelial cells in a 4-day exposure protocol in all participating laboratories. We confirmed that the present single cell suspension method could be used to detect the model chemicals as micronucleus inducers in mouse colonic epithelial cells. Advantages of this method are that experiments are easy to perform and that intact cells can be analyzed. The present study suggested that the colon micronucleus assay proposed here is useful for mechanistic studies of colon carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed2002

Evidence-based infection control in thoracic surgery.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) continues to pose a major threat to the lung and cardiovascular surgery patients. We propose evidence-based infection control (EBIC) against MRSA. METHODS: We conducted a basic study comparing genotyping to cluster analysis using minimal inhibition concentration on 17 drugs for 21 MRSA strains. With or without EBIC using cluster analysis and global evidence, we compared the incidence of postoperative MRSA infection. Notably, we eliminated tweezers stands and emesis basins. RESULTS: Cluster analysis showed a typing sensitivity of 72%. The use of EBIC decreased MRSA cross-infection in the recovery room. A lung surgery series showed an MRSA incidence of 1/190 before and 0/200 after EBIC was introduced. For a cardiovascular surgery series, the MRSA incidence was 2/169 before and 0/84 after EBIC was introduced. Across wards, MRSA among Staphylococcus aureus in patient fell from 68% in 1999 to 57% in 2000. CONCLUSIONS: EBIC consisting of global guidelines and cluster analysis was useful in controlling MRSA in lung and cardiovascular surgery patients.

Cluster Analysis↗
PubMed2002

Myocardial stiffness is determined by ventricular fibrosis, but not by compensatory or excessive hypertrophy in hypertensive heart.

OBJECTIVES: Diastolic dysfunction that determines symptoms and prognosis in patients with systolic dysfunction causes heart failure even in the absence of systolic dysfunction. Our recent studies have suggested that myocardial stiffening is likely to play a crucial role in triggering deleterious cardiac disorder. This study investigated differential contribution of left ventricular (LV) hypertrophy and fibrosis to myocardial stiffening in the pressure-overloaded heart. METHODS: Dahl-Iwai salt-sensitive rats fed on high-salt diet since 7 weeks transit to congestive heart failure at 20 weeks following development of hypertension, LV hypertrophy and fibrosis, and 20 such rats were divided into three groups: rats treated with angiotensin II type 1 receptor antagonist from 8 weeks (n=7), rats treated with calcineurin inhibitor from 8 weeks (n=6), and untreated rats (n=7). RESULTS: Administration of angiotensin II type 1 receptor antagonist and calcineurin inhibitor did not affect blood pressure and allowed the development of compensatory hypertrophy. However, in contrast to the untreated rats, additive and excessive LV hypertrophy was not observed in either of the treated rats. The blockade of angiotensin II kept LV hydroxyproline content, a ratio of type I to type III collagen mRNA levels, collagen solubility and myocardial stiffness constant at the normal level; however, the calcineurin inhibition failed. CONCLUSIONS: Myocardial stiffening may be attributed to progressive collagen accumulation, collagen phenotype shift and enhanced collagen cross-linking, but not to either compensatory LV hypertrophy or LV hypertrophy that progresses from the compensatory stage.

Analysis of Variance↗
PubMedDate not supplied

Revival of effective and safe high-dose mizoribine for the kidney transplantation.

We investigated whether high-dose Mizoribine (MIZ: a water-soluble anti-metabolite), 4-6 mg/kg/d was as effective and safe as mycophenolate mofetil (MMF) for patients after kidney transplantation. Between January 2001 and December 2005, 36 recipients at a stable phase more than one month passed after transplantation underwent conversion from MMF to MIZ, two from Azathioprine to MIZ, and two cases on MIZ from the beginning. There were 24-male and 16-female patients whose average age was 43.3 yr old and average weight was 54.0 kg. The types of transplantations were living donor renal transplantation 25, cadaveric renal transplantation 11, and simultaneous pancreas-kidney transplantation four examples. Of these, 33 patients were on Tacrolimus-based triple regimen and seven patients on Cyclosporine A base. The drugs used together with MIZ were basically the same as those before conversion. The reasons for conversion to MIZ were infection in 18 cases (45.0%), bone marrow suppression in nine cases (22.5%) and diarrhea in eight cases (20.0%), and post-transplant lymphoproliferative disorder in one case (2.5%). We initiated 4-6 mg/kg/d of MIZ divided twice a day depending on the serum creatinine (sCr) value of each patient. There was no big difference in the sCr value before and after MIZ administration in each individual patient, 1.79 +/- 1.37 and 1.65 +/- 1.30 mg/dL, respectively. A 12 h pharmaco-kinetic study of MIZ revealed that a peak value reached 2.87 microg/mL on average at three h (C3) followed by a slow decrease afterward. Acute rejection occurred in two cases and adverse effects were seen in five cases. The results of analysis of 349 points divided into three groups by renal function were as follows; poor renal function Group A revealed a trough level of 2.21 +/- 0.99 microg/mL and dosage 2.20 +/- 1.06 mg/kg, good renal function Group B had a trough level of 1.06 +/- 0.82 microg/mL and dosage 4.40 +/- 1.72 mg/kg, and excellent function Group C had a trough level of 0.92 +/- 0.55 microg/mL and dosage of 4.36 +/- 1.08 mg/kg. High-dose MIZ 4-6 mg/kg/d is an anti-metabolite having an equivalent immunosuppressive effect, fewer serious adverse events and good cost-effectiveness as MMF even for patients with prolonged hemodialysis period and declined digestive function in Japan.

Adolescent↗