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Biomedical subjects

N Kaneko

Publications and source records attributed to N Kaneko.

At least 73 records · Page 4Linked to original sources

[Early steroid withdrawal after kidney transplantation].

BACKGROUND: The side effects of steroid are serious problems in renal transplant patients. However, withdrawal of steroid has been controversial. We evaluated the benefits and risk of early steroid withdrawal after renal transplantation. PATIENTS AND METHODS: The outcomes of early steroid withdrawal from triple immunosuppressive drug therapy were analyzed in four living related and one cadaveric renal transplant recipients. The dosage of steroid was gradually reduced and the time of steroid withdrawal after transplantation was 5 to 7.5 months. RESULTS: Four Patients have been able to be free from steroid and maintained stable graft functions and normal urinary findings for 14 to 33 months after withdrawal. The findings of rejection were not observed in the graft specimens obtained by serial biopsies. One patient who received a living related graft developed an increase in serum creatinine level and proteinuria two weeks after discontinuation of steroid. The serum creatinine level returned to that before withdrawal and proteinuria disappeared by steroid readministration. Long term side effects of steroid were not observed in 4 patients with successful steroid withdrawal. CONCLUSION: These results suggest that steroid withdrawal about 6 months after transplantation can be accomplished without jeopardizing graft function in selected renal transplant recipient and the withdrawal in the early stage is preferred for reducing the side effects. Careful and long-term follow up are required to assess the further risk and benefit of steroid withdrawal on immunosuppressive morbidity.

Adult↗

[The efficacy of Turbuhaler dry powder inhaler in Japanese asthma--measurement of peak inspiratory flow when using Turbuhaler].

Inhaled antiasthmatic agents can be effective, but their efficacy depends on the delivery system and on inhalation technique. The dry powder inhaler Turbuhaler is being evaluated clinically, and correct inhalation technique with this device has been shown to be easy to teach. To find out whether this device could be useful in Japan, we studied inspiratory flow and inhalation technique with the Turbuhaler in Japanese patients with asthma. Of the 105 patients studied, 80 patients (76.2%) used the Turbuhaler correctly after only one practice session; 58 patients (55%) found it easy or very easy to use, and 19 patients (18%) found it difficult to use. The mean peak inspiratory flow for all patients was 61 L/min. Peak inspiratory flow was less than 30 L/ min in only two patients, both of whom were women over 65 years old. Peak inspiratory flow did not correlate with other indices of pulmonary function. In summary, inspiratory flow in Japanese patients with asthma was sufficient for the Turbuhaler to be effective, and these patients soon learned to use the device even though they had no previous experience with a dry powder inhaler. Therefore, the Turbuhaler should be clinically useful in Japan.

Administration, Inhalation↗

The role of cardiac mitochondria in the regulation of intracellular calcium during ischemia and reperfusion: X-ray microanalysis using freeze-dried sections.

The calcium concentration in papillary muscles was measured by X-ray microanalysis in order to clarify the role played by mitochondria in intracellular calcium regulation during ischemia and reperfusion. Rat hearts perfused by the Langendorff method were rapidly frozen prior to and during ischemia, as well as following reperfusion. Sections prepared by cryoultramicrotomy were freeze-dried, carbon-coated, and analyzed in an electron microscope. A new freeze-drying procedure was developed, in which the ultrastructure was well-preserved, with sarcomeres, triads, and mitochondria easily recognized. Calcium accumulation into the mitochondria occurred during 30-min ischemia (29.7 +/- 17.0 mmol/kg dry weight) and increased further after 15-min reperfusion (157.1 +/- 104.5), the calcium concentration decreased after 60-min reperfusion (58.1 +/- 29.0). However, the calcium concentration in the cytosol did not change significantly. It is thought that mitochondrial calcium accumulation is reversible, to a certain degree, and that the mitochondria play a part in intracellular calcium regulation in pathological states.

Animals↗

Cytomegalovirus-associated hepatitis and duodenal ulcer in kidney allograft recipients.

We report here on two patients with kidney allografts who had hepatitis and duodenal ulcer caused by cytomegalovirus. In one case, hepatosplenomegaly and jaundice appeared after high fever lasting for ten days. Laboratory examinations showed liver dysfunction and lymphocytosis with atypical forms. Virological studies revealed cytomegalovirus infection and we successfully treated the patient with human interferon-beta. In the other case, duodenal bleeding followed by interstitial pneumonia occurred at the 54th day after transplantation. Bleeding from the small duodenal ulcer did not stop in spite of conservative and endoscopic therapies, and gastrectomy was performed. Histologically many epithelial cells with intranuclear inclusions were found around the ulcer. Virological studies showed elevation of antibody titres to cytomegalovirus which was isolated from the urine and oropharyngeal secrete. After gastrectomy and treatment with ganciclovir, the general condition improved and graft function was maintained. Our experience with these cases suggests that aggressive diagnostic investigations for cytomegalovirus infection are essential in patients with organ allografts who present liver and gastrointestinal lesions.

Adult↗

Hepatocyte growth factor is the most potent endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture.

Various growth factors are suggested to be involved in gastric mucosal repair. Our previous studies have shown that exogenous hepatocyte growth factor (HGF) has a proliferative effect on gastric epithelial cells. In the present study, comparison of the maximum proliferative effects and the optimum concentrations of several growth factors revealed that HGF was the most potent mitogen for gastric epithelial cells, as is the case for hepatocytes. Restitution of gastric epithelial cell monolayers was assessed using a round wound restitution model. HGF was the most effective agent for facilitating gastric epithelial restitution among those tested. A binding assay revealed specific binding of HGF to its receptor on gastric epithelial cells. Northern blot analysis confirmed the expression of specific HGF receptor mRNA (c-met) by gastric epithelial cells but not by gastric fibroblasts. To investigate endogenous HGF production, we determined the effect of gastric fibroblast-conditioned medium on epithelial proliferation and restitution. The conditioned medium produced similar effects to HGF and its activity was neutralized by an anti-HGF antibody. In addition, expression of HGF mRNA was detected in gastric fibroblasts but not in gastric epithelial cells. Our immunohistochemical study confirmed these in vitro data by means of demonstrating the existence and localization of HGF at human native gastric mucosa. HGF was localized at fibroblasts under the epithelial cell layer around gastric ulcers. These results suggest that HGF may be a potent endogenous promotor of gastric epithelial cell proliferation and migration, and may contribute to gastric mucosal repair through a paracrine mechanism.

Animals↗

[Interleukin-2 activity in monocrotaline-treated rat lungs].

To study the relationship between cytokines and the development of monocrotaline-induced pulmonary hypertension, monocrotaline was given and interleukin-2 was measured. The amount of interleukin-2 produced by pulmonary cells obtained by bronchoalveolar lavage was high only on the 14th day after monocrotaline injection (p < 0.01). This suggests that many kinds of cells in the monocrotaline-treated rat lung were activated by cytokines, and that these interactions play an important role in the development of monocrotaline-induced pulmonary hypertension in rats.

Animals↗

[Changes in smooth muscle cell proliferation in pulmonary arteries of rats given monocrotaline].

To study the relationship between proliferation of smooth muscle cells and structural changes in arteries of rats given monocrotaline, light microscopy with immunohistochemistry for bromodeoxyuridine (BrdU) was done after a single subcutaneous injection of monocrotaline. In increase in DNA synthesis in smooth muscle cells was seen from 3 days until 14 days after administration. Since this increase was seen before pulmonary hypertension and medial thickness developed some mechanisms that induce proliferation of pulmonary atrial smooth muscle may have been triggered soon after monocrotaline injection.

Animals↗

[ST segment re-evaluation immediately after successful recanalization in acute myocardial infarction: predictor for poor recovery of left ventricular regional wall motion].

The value of recanalization therapy in restoring risk area after acute coronary occlusion is well documented. However, some cases show poor recovery of left ventricular function regardless of early reperfusion. This study investigated the use of ST segment re-elevation immediately after recanalization in patients with acute myocardial infarction as a predictor of recovery of regional wall motion and risk area. ST segment change and regional wall motion were compared in 16 patients with [ST(+)] and 8 patients without ST segment re-elevation [ST(-)] after successful recanalization within 6 hours from onset. ST segment re-elevation was defined as 0.2 mV or more in at least two contiguous leads immediately after recanalization. Wall motion was measured from single-plane ventriculograms performed in the acute and chronic (3-4 weeks later) phases in the infarct regions by the centerline method. Hypokinesis was defined as more than -2SD/chord(c) below normal and expressed as SD/c for the severity of regional wall motion and chord number(CN) for risk area. Time from symptom onset to recanalization did not differ between the two groups [3.8 +/- 1.2 hours for ST(-), 3.9 +/- 0.9 hours for ST(+), not significant]. In the ST(-) group, regional wall motion improved from -2.92 +/- 0.33 to -1.45 +/- 0.81 SD/c (p = 0.0005) and risk area decreased from 29.8 +/- 16.6 to 9.5 +/- 15.7 CN (p = 0.005) in the acute and chronic phases, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Purification of cardiac annexin V from the beagle dog heart and changes in its localization in the ischemic rat heart.

We isolated and purified 35 kDa protein from the myocardium of the beagle dog and identified it to be annexin V from partial amino acid sequence determination. It was confirmed that anticanine cardiac annexin V rabbit polyclonal antibody, which was produced using the 35 kDa protein, cross-reacts with annexin V of the myocardium, lung, liver, kidney, and brain of the rat. The localization of cardiac annexin V and the effect of ischemia for 30-180 min in the rat were immunohistochemically studied with the use of the Langendorff perfusion heart. In the normal myocardium, annexin V, accompanied by cross-striation, was observed throughout the cell. In ischemia of 30 min, extracellular leakage of annexin V was observed with uneven staining in the cytoplasm. When the ischemic time exceeded 60 min, annexin V was observed in the cell membrane with a decrease of annexin V in the cytoplasm. Also, extracellular leakage of annexin V was observed prominently. In ischemia for 180 min, almost all the annexin V in the cytoplasm disappeared. These results suggest that the level of ischemia can be estimated from the changes in localization of annexin V.

Animals↗

Intravenous diltiazem versus isosorbide dinitrate for unstable angina: comparison of coronary angiographic morphology in the unstable and stabilized states.

BACKGROUND: The efficacy of intravenous infusion of diltiazem was compared with that of isosorbide dinitrate (ISDN) for the early treatment of unstable angina. METHODS: Sixty-four patients with at least 70% organic stenosis of the culprit artery and prolonged rest angina were enrolled. Coronary angiography was performed on admission. Subsequently, patients were randomly assigned to receive either intravenous diltiazem or ISDN. Coronary angiography was repeated when the angina was under control, and the findings were compared with those on admission. RESULTS: Diltiazem was more effective than ISDN, and symptoms were resolved in 84% of the diltiazem group compared with 47% of the ISDN group (P = 0.0038). Repeat coronary angiography showed that the degree of stenosis remained unchanged in the majority of patients (n = 47, 75.8%). There was no difference between the two groups with regard to the coronary angiographic findings. CONCLUSIONS: Since diltiazem was more effective than ISDN even though the coronary angiographic findings of the two groups were similar, it is possible that some action other than vasodilatation (such as a direct protective effect on the myocardium) may be responsible for the remission of unstable angina.

Aged↗

[Relationship between the converting ability of liver microsomes and monocrotaline-induced pulmonary hypertension in male, female and castrated male rats].

It is well known that the initial reaction of monocrotaline-induced pulmonary hypertension in rats (MPH) is injury to the endothelial cells of pulmonary vascular bed by monocrotaline-pyrrole (MP), which is converted from monocrotaline (M) by cytochrome P450 monooxygenase in hepatic microsomes. It is also known that the degree of MPH differs between sexes. The mechanisms of MPH remain, however, to be elucidated. The purpose of this study is to clarify the relationship between the converting ability of hepatic microsomes and the sexual difference in MPH using castrated male rats. A 40 mg/kg dose of M was given to fifteen 6 week-old male, twelve 6 week-old female and fifteen 6 week-old castrated male, Sprague-Dawley, rats. The castration was done at three weeks of age. Four weeks after M administration, the right ventricular systolic pressure (RVSP) and the right ventricular to total ventricular weight ratio (RV/T) were measured as indices of pulmonary hypertension. Livers were taken from six 6 week-old male, six, 6 week-old female and six 6 week-old castrated male, Sprague-Dawley, rats and then homogenized and centrifuged to extract hepatic microsomes. M, at 3.3 mM, was added to concentrated hepatic microsomes (0.25 to 1.5 mg/ml) in order to produce MP. The concentration of the MP was measured using a modification of Mattock's method. The mean value of RVSP was 86.5 mmHg in males, 59.6 mmHg in females and 73.9 mmHg in castrated males. The mean value of RV/T was 0.453 in males, 0.358 in females and 0.403 in castrated males.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Bioactive glass promoted formation of nodules in periodontal-ligament fibroblasts in vitro.

The effects of bioactive glass and vitamin D3 on cultured fibroblasts derived from periodontal-ligament, with respect to their proliferation and alkaline-phosphatase activity were studied. The cells were cultured with or without the bioactive glass and/or vitamin D3, then the number and alkaline-phosphatase activity of the cells were measured periodically until the 33rd day. Formation of mineralized deposits was assessed by staining with alizarin red and von Kossa staining techniques. Fewer fibroblasts grew when they were cultured in the presence of bioactive glass and/or vitamin D3 as compared to those cultures without them. Alkaline-phosphatase activity was greater in the fibroblasts cultured with bioactive glass and vitamin D3 than in the cells grown without them. Mineralized deposits assessed by alizarin red and von Kossa staining techniques were observed microscopically around the fibroblasts cultured with bioactive glass and/or vitamin D3. A nodule visible after drying was evident only when both bioactive glass and vitamin D3 were present in culture. The results showed that although the bioactive glass and vitamin D3 decreased cell proliferation, they increased the alkaline-phosphatase activity of the fibroblasts which formed a nodule, suggesting an effect which might be useful for implant materials.

Alkaline Phosphatase↗

[Significance of Tc-99m pyrophosphate accumulation in unstable angina: clinical characteristics and evidence for myocardial stunning].

Tc-99m pyrophosphate (PYP) and Tl-201 simultaneous dual energy single photon emission computed tomography (SPECT) were performed for 33 patients with clinically diagnosed unstable angina. Twenty-two patients (76%) showed PYP accumulation in the myocardium (PYP+group). Clinical features, types of unstable angina, electrocardiographic changes during and after the anginal attack, and serial creatine kinase (CK) sampling data were reviewed and compared in the 2 groups. Selective coronary angiography was performed in all patients, and contrast left ventriculography was carried out in 29 patients both in unstable and stable states. In the study of left ventriculograms, the ejection fraction (EF) was calculated by the area-length method and the wall motion abnormality index was calculated by the centerline method. The PYP(+)group differed significantly from the PYP(-)group in several features as follows: 1) the "new angina at rest" type of unstable angina was more frequent in the PYP(+)group than in the PYP(-)group. The ratios of new angina at rest/effort angina (including new angina of effort and angina of effort with changing pattern) were 16/6; 2/9 for the PYP(+) and (-)groups, respectively (p < 0.05). 2) ST elevation during the heart attack was seen more in the PYP(+)group. The ratios of ST elevation/ST depression were 13/22 (59%); 5/22 (23%) for the PYP(+)group, and 2/11 (18%); 7/11 (64%) for the PYP(-)group, respectively (p < 0.05). 3) EF was improved in the PYP(+) group to the normal range. EF in the PYP(+)group changed from 57 +/- 12 in the unstable state to 62 +/- 11% in the stable state (p < 0.02), while that of the PYP(-)group showed no significant difference between the unstable state (59 +/- 9%) and the stable state (59 +/- 11%). 4) Wall motion abnormality index (WMI) in the PYP(+)group was poorer than in the PYP(-)group, but it improved markedly in one month to the same level as that of the PYP(-)group. WMI in the PYP(+)group in the unstable state (21.7 +/- 26.2) was worse than that in the PYP(-)group in unstable state (5.7 +/- 8.2) (p < 0.001). WMI in the PYP(+)group in the unstable state markedly improved in the stable state (from 21.7 +/- 26.2 to 8.4 +/- 19.8) (p < 0.025); whereas, WMI of the PYP(-)group showed no significant improvement (from 5.7 +/- 8.2 to 15.5 +/- 19.6). These data suggest that the area showing PYP(+) may represent stunned myocardium.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina, Unstable↗