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Masato Nakamura

Publications and source records attributed to Masato Nakamura.

At least 91 records · Page 5Linked to original sources
PubMed2003

Combined assessment of cardiac systolic dysfunction and coronary atherosclerosis used to predict future cardiac deaths after starting hemodialysis.

BACKGROUND/AIMS: Identification of end-stage renal disease (ESRD) patients at high risk for cardiac events is important for clinical dialysis management. The present study determined whether the combination of cardiac function and coronary atherosclerosis could predict future cardiac events after starting renal replacement therapy (RRT). METHODS: We prospectively assessed left ventricle ejection fraction (EF) and Gensini score (GS) using angiographic severity of coronary atherosclerosis in 88 consecutive ESRD patients [mean age 62 years; 69 males (78%); 55 patients (64%) with diabetic nephropathy] at the initiation of RRT. EF was analyzed by echocardiogram, and GS was scored by coronary angiography within 3 months after starting RRT. The study end point was cardiac death. For analysis of the association between cardiac death and EF and GS measures, the univariate and multivariate Cox proportional hazards model was used. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value, and accuracy of event-free prediction were evaluated. RESULTS: Twenty-four patients (27%) had low cardiac function (EF <50%; low EF) and 44 patients (50%) had severe coronary atherosclerosis (GS >15; high GS). During a follow-up period of 3 years, cardiac death occurred in 21 patients (24%). The PPV of low EF and high GS was 42 and 39%, respectively; the highest PPV (53%) was obtained when low EF and high GS were combined. The cumulative survival rate at 5 years in patients with both low EF and high GS was significantly lower than those with high EF and low GS (91 vs. 22%, p < 0.0005). CONCLUSION: The combined assessment of cardiac function and coronary atherosclerosis at the initiation of RRT strongly predicts future cardiac events.

Cause of Death↗
PubMed2003

Bimodal circadian secretion of melatonin from the pineal gland in a living CBA mouse.

Circadian melatonin secretion is the best-known output signal from the circadian pacemaker in the suprachiasmatic nucleus that indicates internal conditions of the body. We have established a system that enables long-term monitoring of melatonin secretion by implanting a transverse microdialysis probe in or near the pineal gland in a freely moving mouse. This in vivo method enabled continuous measurement of melatonin secretion over a period of >20 days in individual CBA mice, with simultaneous recording of the locomotor activity. Pineal melatonin secretion was completely matched to the circadian change of locomotor activity, and for the light-induced phase shift, the shift of melatonin secretion was clearer than the shift of locomotor rhythm. This analysis allowed us to detect rhythm with a high sensitivity: two peaks of daily secretion were observed, with the first small peak at the day-night transition time and the second large peak at midnight. The large nighttime peak was suppressed by tetrodotoxin, a Na+ channel blocker, and enhanced by both phenylephrine and isoproterenol, alpha- and beta-adrenergic agonists, whereas daytime melatonin levels were not affected by tetrodotoxin infusion. This finding suggests that, in CBA mice, melatonin release at night is activated by adrenergic signaling from the superior cervical ganglion, but the enhancement of melatonin during daytime is not mediated by neuronal signaling.

Animals↗
PubMed2003

Vascular endothelial growth factor 121 and 165 in the subacromial bursa are involved in shoulder joint contracture in type II diabetics with rotator cuff disease.

Vascular endothelial growth factor (VEGF) is a glycoprotein that plays an important role in neovascularization and increases vascular permeability. We reported that VEGF is involved in motion pain of patients with rotator cuff disease by causing synovial proliferation in the subacromial bursa (SAB). The present study investigates whether VEGF is also involved in the development of shoulder contracture in diabetics with rotator cuff disease. We examined 67 patients with rotator cuff disease, including 36 with complete cuff tears, 20 with incomplete tears, and 11 without apparent tears (subacromial bursitis). The patients were into groups according to the presence or absence of diabetes (14 type II diabetics and 53 non-diabetics). Specimens of the synovium of the SAB were obtained from all patients during surgery. Expression of the VEGF gene in the synovium of the subacromial bursa was evaluated by using the reverse transcriptase polymerase chain reaction. The VEGF protein was localized by immunohistochemistry, and the number of vessels was evaluated based on CD34 immunoreactivity. The results showed that VEGF mRNA was expressed in significantly more diabetics (100%, 14/14) than in non-diabetics (70%, 37/53) (P=0.0159, Fisher's test). Investigation of VEGF isoform expression revealed VEGF121 in all 14 diabetics and in 37 of the 53 non-diabetics, VEGF165 in 12 of the 14 diabetics and in 21 of the 53 non-diabetics, and VEGF189 in 1 of the 14 diabetics and in 2 of the 53 non-diabetics. No VEGF206 was expressed in either group. VEGF protein was localized in both vascular endothelial cells and synovial lining cells. The mean number of VEGF-positive vessels and the vessel area were also significantly greater in the diabetics (p<0.015, Mann-Whitney U test). Synovial proliferation and shoulder joint contracture were more common in the diabetics (P=0.0329 and P=0.073, respectively; Fisher's test). The mean preoperative range of shoulder motion significantly differed in terms of elevation between two groups: 103.8 degrees in diabetics and 124.9 degrees in no diabetics (p=0.0039 Mann-Whitney U test). In contrast, external rotation did not significantly differ: 44 degrees in diabetics and 49 degrees in non-diabetics (p=0.4957, Mann-Whitney U test). These results suggest that VEGF121 and VEGF165 expression in the SAB is responsible for the development of shoulder joint contracture, especially in elevation, among type II diabetic patients with rotator cuff disease.

Acromioclavicular Joint↗
PubMed2003

Angiographical severity of coronary atherosclerosis predicts death in the first year of hemodialysis.

BACKGROUND: Cardiac deaths and events tend to cluster within the early-phase after starting dialysis. Our goal is to clarify the influence of severity of coronary atherosclerosis on early-phase death after starting hemodialysis (HD) therapy. PATIENTS AND METHODS: Eighty-three consecutive patients [mean age 62 years; male/female 64/19; diabetic nephropathy in 50 (54%)] with end-stage renal disease who admitted to our hospital to initiate regular HD treatment, and then received coronary angiography within 3 months after first dialysis therapy, were eligible for this study. Angiographical severity of coronary atherosclerosis was scored by numerically using Gensini scoring system. The patients who died within one year from starting HD were compared with those who survived as control by means of logistic regression analysis. RESULTS: Of 83 patients, 12 (14%) died less than one year after starting dialysis therapy. Of these 12 patients, nine died for cardiac causes. Confirmed predictors of death from cardiac cause were older age (>70 years), lower mean blood pressure (<100 mmHg), presence of ischemic heart disease (IHD), myocardial infarction (MI), angina pectoris (AP), chronic heart failure (CHF), poor cardiac function, abnormal wall motion of left ventricule (LV) and angiographical severity of coronary atherosclerosis by univariate model. Adjusting for confounding variables by multivariate model, only severity of coronary atherosclerosis (Gensini score >40 points) had a powerful influence, increasing risk for cardiac cause of early-phase death by about 17 times. CONCLUSIONS: Severity of coronary atherosclerosis predicts death in the first year of HD. These findings suggest that the strategy for prevention of coronary atherosclerosis should be instituted during the early phase of chronic renal failure.

Adult↗
PubMed2003

Differences in cytochrome P450 forms involved in the metabolism of N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine monohydrochloride (NE-100), a novel sigma ligand, in human liver and intestine.

N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine monohydrochloride (NE-100) has been developed to treat subjects with schizophrenia. This drug is mainly excreted in the form of oxidative metabolites. In the present study, identification of p450 forms involved in the metabolism was carried out using human livers and intestinal microsomes (HLM and HIM). Eadie-Hofstee plots for NE-100 disappearance in HLM were biphasic, thus indicating the involvement of at least two p450 forms. The metabolism of NE-100 was mediated with recombinant CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. A significant correlation was observed between activities of NE-100 metabolism and dextromethorphan O-demethylation (a specific activity for CYP2D6) or testosterone 6beta-hydroxylation (a specific activity for CYP3A4) in HLM. The activity of NE-100 metabolism was inhibited by approximately 80% by an anti-CYP2D6 antibody and only by quinidine among the p450-selective inhibitors at a low substrate concentration (0.1 microM). In contrast, with a high substrate concentration (10 microM), the activity was inhibited by an anti-CYP3A4 antibody and by ketoconazole. On the other hand, in HIM, the Eadie-Hofstee plots for NE-100 disappearance were monophasic, and the metabolism was strongly inhibited by an anti-CYP3A4 antibody and by ketoconazole but not by other inhibitors used. These results strongly suggest that NE-100 has different profiles regarding metabolism between liver and intestine. During absorption, NE-100 is mainly metabolized by CYP3A4 in the intestine and thereafter by CYP2D6 in the liver in the presence of therapeutic doses.

Anisoles↗
PubMed2003

Monoclonal antibodies that distinguish antigenic variants of canine parvovirus.

Canine parvovirus (CPV) is classified as a member of the feline parvovirus (FPV) subgroup. CPV isolates are divided into three antigenic types: CPV type 2 (CPV-2), CPV-2a, and CPV-2b. Recently, new antigenic types of CPV were isolated from Vietnamese leopard cats and designated CPV-2c(a) or CPV-2c(b). CPV-2c viruses were distinguished from the other antigenic types of the FPV subgroup by the absence of reactivity with several monoclonal antibodies (MAbs). To characterize the antigenicity of CPV-2c, a panel of MAbs against CPV-2c was generated and epitopes recognized by these MAbs were examined by selection of escape mutants. Four MAbs were established and classified into three groups on the basis of their reactivities: MAbs which recognize CPV-2a, CPV-2b, and CPV-2c (MAbs 2G5 and 20G4); an MAb which reacts with only CPV-2b and CPV-2c(b) (MAb 21C3); and an MAb which recognizes all types of the FPV subgroup viruses (MAb 19D7). The reactivity of MAb 20G4 with CPV-2c was higher than its reactivities with CPV-2a and CPV-2b. These types of specificities of MAbs have not been reported previously. A mapping study by analysis of neutralization-resistant mutants showed that epitopes recognized by MAbs 21C3 and 19D7 belonged to antigenic site A. Substitution of the residues in site B and the other antigenic site influenced the epitope recognized by MAb 2G5. It was suggested that the epitope recognized by MAb 20G4 was related to antigenic site B. These MAbs are expected to be useful for the detection and classification of FPV subgroup isolates.

Animals↗
PubMed2003

Metabolism of N,N-dipropyl-2-[4-methoxy-3-(2-phenyl-ethoxy)-phenyl]-ethyl-amine-monohydrochloride (NE-100), a novel sigma ligand: contribution of cytochrome P450 forms involved in the formation of individual metabolites in human liver and small intestine.

In the present study, human cytochrome P450 (CYP) forms involved in producing the primary metabolites of NE-100 were identified. Major metabolites of NE-100 in human liver microsomes (HLM) were N-depropylation of NE-100 (NE-098), p-hydroxylation of phenyl group of NE-100 (NE-152), m-hydroxylation of phenyl group of NE-100 (NE-163) and O-demethylation of NE-100 (NE-125). Judging from the correlation and inhibition studies, NE-125 and NE-152+163mix formations were predominantly mediated by CYP2D6 and NE-098 formation was mediated by multiple CYP forms at a low NE-100 concentration (0.1 microM) in the HLM. According to relative activity factor (RAF) approaches, all these reactions were predominantly catalyzed by CYP2D6 at a substrate concentration assuming a plasma level of NE-100 (K(m)>>S) in case of the human liver. Depending on the increase in NE-100 concentrations, the rate of contribution for NE-098 and NE-152+163mix formations increased in CYP3A4, although the predominant contribution of CYP2D6 for NE-125 formation did not change. In human intestinal microsomes (HIM), NE-100 was mainly metabolized to NE-098 and NE-152+163mix by CYP3A4. The intrinsic clearance for their formations in HIM was 3.2 and 14.9 times less than those in HLM, respectively, and no formation of NE-125 was observed in HIM. These results strongly suggest that CYP2D6 is the predominant form for NE-100 metabolism in the human liver in in vivo conditions (K(m)>>S) and the liver plays a more important role than does the small intestine in the first pass metabolism.

Journal Article↗
PubMed2003

Epidermal growth factor receptor expression in human pancreatic cancer: Significance for liver metastasis.

Pancreatic cancer is a malignant tumor with an extremely poor prognosis. The mechanisms of the aggressive growth and metastasis are not yet extensively understood. Over-expression of epidermal growth factor receptor (EGFR) was suggested to be associated with malignant transformation of pancreatic cancer. We examined EGFR expression in 77 cases of invasive ductal adenocarcinoma of the pancreas, and analyzed the relation between the EGFR expression pattern and clinicopathological factors. EGFR immunoreactivity was detected in 41.6% (32/77) of human pancreatic cancers; i.e. diffuse expression in 32.5% (25/77) and focal expression in 9.1% (7/77). The EGFR expression was associated with gender (p<0.05), histological differentiation (p<0.05) and metastatic status of TNM classification (p<0.01). The observations suggested that EGFR expression plays important roles in metastasis, especially liver metastasis and recurrence of human pancreatic cancer.

Carcinoma, Pancreatic Ductal↗
PubMed2003

Reversal of drug resistance mediated by hammerhead ribozyme against multidrug resistance-associated protein 1 in a human glioma cell line.

We examined the effects of suppressing multidrug resistance-associated protein 1 (MRP1) gene expression in a human glioma cell line U87MG. Hammerhead ribozymes, designed to cleave MRP1 mRNA (alphaMRP1-Rz), were transfected into the U87MG cells. The U87MG/alphaMRP1-Rz cells were significantly sensitive to nitrosourea (ACNU) and doxorubicin (DOX) compared with the U87MG cells (p<0.01 and p<0.05, respectively, unpaired t-test). There was no significant difference in the expression of other human genes between the U87MG/alphaMRP1-Rz and controls by cDNA array. The hammerhead ribozyme-mediated specific suppression of MRP1 was sufficient to reverse the resistance of ACNU and DOX in the human glioma cell line.

Antibiotics, Antineoplastic↗
PubMed2003

The impact of cutting balloon angioplasty for the treatment of diffuse in-stent restenosis.

OBJECTIVE: To determine the comparable safety and efficacy of cutting balloon angioplasty (CBA) and balloon angioplasty (BA) for diffuse in-stent restenosis (ISR). BACKGROUND: Previous studies have found that diffuse-type ISR predicts recurrence of ISR. The efficacy of CBA in this clinical setting is incompletely documented. METHODS AND RESULTS: One-hundred and seven consecutive diffuse ISR lesions (length > 10 mm) in 104 patients treated by CBA or BA were retrospectively analyzed. CBA was used in 61 lesions and BA in 46 lesions. Initial success (residual restenosis 30% with no major complications) was achieved in 99% of cases in each group. Follow-up angiography was performed in all patients at 131 93 days. Although the percent diameter stenosis after CBA was lower than after BA (19 12% versus 27 12%; p = 0.001), intravascular ultrasound (IVUS) or other QCA data were similar in the 2 groups. In follow-up angiography, recurrent restenosis rate was not statistically different between CBA (34%) and BA (52%); however, recurrent diffuse ISR was lower in the CBA group (20%) than the BA group (48%; p = 0.01). Lesion length at follow-up in the CBA group was smaller compared to the BA group (15.9 7.3 mm versus 24.2 14.4 mm; p < 0.05), while lesion length before procedure was similar. CONCLUSION: CBA for ISR is safe and effective with favorable long-term outcomes. This effect is mainly due to shortening lesion length.

Adult↗
PubMed2003

The modifier subunit of glutamate cysteine ligase (GCLM) is a molecular target for amelioration of cisplatin resistance in lung cancer.

It is unclear whether a subunit of glutamate cysteine ligase [a modifier subunit (GCLM) and a catalytic subunit (GCLC)] is an effective target for ameliorating cisplatin (CDDP)-resistance. We inhibited each subunit of GCL mRNA using a specific ribozyme (M-Rz and C-Rz) in the pulmonary adenocarcinoma cell line A549. GCL activity was suppressed by the ribozyme. CDDP-resistance was more effectively ameliorated when GCLM rather than GCLC was inhibited. GCLM is a potentially more effective pharmacologic target for ameliorating CDDP-resistance in non-small cell lung cancer than GCLC.

Antineoplastic Agents↗
PubMed2003

[A case of successful treatment of advanced hepatocellular carcinoma with tumor thrombi in the major portal branches and inferior vena cava with combined intraarterial 5-fluorouracil, adriamycin and cisplatin therapy].

The patient is a 75-year-old male. Abdominal ultrasound tomography in June 2002 revealed hepatocellular carcinoma with intrahepatic metastasis (IM3) and tumor thrombi (Vp4, Vv3) at S4 in the major portal and hepatic vein. From July 2002, he received hepatic arterial infusion therapy (FAP: 5-fluorouracil, CDDP and adriamycin) for these lesions. In December 2002, these lesions had disappeared completely after 6 sessions of arterial infusion therapy. The patient is still alive with no recurrence after 2 years since the beginning of this treatment. Recently, we treated 9 patients with combined arterial infusion chemotherapy (FAP), and the response rate (CR and PR) was 44% and no major side effect was observed. In conclusion, some patients may obtain longer survival through this treatment, even in cases of advanced HCC with tumor thrombus in the major trunks of portal vein and/or hepatic vein.

Aged↗
PubMed2003

[A case of long-term survival with TAE resistant multiple recurrence HCC successfully treated by hepatic resection].

A 55-year-old female was admitted to our hospital for a third recurrence of hepatoma. She was treated with transcatheter arterial embolization (TAE) in April and November 1996. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed multiple tumors of S4/S8 and S7 in the liver. After the third TAE using SMANCS, Lipiodol and Spongel, abdominal CT revealed insufficient Lipiodol retention and the in efficacy of this treatment. A right lobectomy of the liver was performed for the TAE resistant multiple recurrence of HCC. After the surgery, the patient survived for over 5 years with no recurrence. It appears that this surgery may be a useful modality for TAE resistant multiple recurrence hepatoma in cases of good liver function and lesions limited to the hemi lobe.

Antineoplastic Agents↗
PubMed2002

Neuropilin 1 and neuropilin 2 co-expression is significantly correlated with increased vascularity and poor prognosis in nonsmall cell lung carcinoma.

BACKGROUND: Cell-retained isoforms of vascular endothelial growth factor A (VEGF-A) have been reported to play an essential role in tumor progression through stromal neovascularization in malignant solid tumors. While more than 95% of nonsmall cell lung carcinoma (NSCLC) expresses cell-retained VEGF-A isoform, the clinicopathologic implications of neuropilin (NRP), considered the specific receptor for limited types of VEGF-A isoform, are not well understood. METHODS: The authors examined NRP1 and NRP2 mRNA expression in 68 NSCLCs and 15 extraneoplastic tissues by a densitometry-assisted, semi-quantitative reverse transcription-polymerase chain reaction. The authors determined the distinct expression of NRPs using the expression level of NRPs relative by optical density to beta2-microglobulin. The authors also investigated VEGF-A isoforms, their receptors, and the clinical implications. Vascularity of NSCLC was morphologically estimated on sections immunostained with anti-CD34 antibody. RESULTS: Eleven of 15 extraneoplastic specimens showed NRP1 expression (73.3%) and 8 showed NRP2 expression (53.3%). The expression level of NRP1 or NRP2 of neoplasmic tissue was higher than that of extraneoplastic tissues (P < 0.01, Mann-Whitney U test). Fifty-five and 44 NSCLCs expressed NRP1 and NRP2, respectively. Forty patients co-expressing NRP1 and NRP2 showed significantly poorer prognosis and increased vessel counts as compared to those 28 cases without co-expression (P < 0.05, log-rank test; P < 0.05, Mann-Whitney U test). CONCLUSIONS: The co-expression of NRP1 and NRP2 genes is significantly correlated with tumor progression through neovascularization in NSCLC. These results suggest that both NRP1 and NRP2 are key molecules for stromal vascularization by cell-retained VEGF in NSCLC.

Carcinoma, Non-Small-Cell Lung↗