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Biomedical subjects

Masato Nakamura

Publications and source records attributed to Masato Nakamura.

At least 109 records · Page 6Linked to original sources

Intravascular ultrasonic comparisons of mechanisms of vasodilatation of cutting balloon angioplasty versus conventional balloon angioplasty.

Intimal hyperplasia after balloon dilatation may be related to the severity of vascular injury, and cutting balloon angioplasty (CBA) may reduce vascular injury. The present study investigated the mechanism of vasodilation by CBA. Intravascular ultrasound examination was performed before and after intervention in 40 lesions treated with CBA and in 25 lesions treated with conventional balloon angioplasty. Intravascular ultrasound measurements included the vessel area, luminal area, and plaque area. Vessel expansion was evaluated as the ratio of the postprocedural vessel area to that before intervention. The vessel area was 13.9 +/- 3.2 and 14.8 +/- 3.2 mm(2) after CBA versus conventional angioplasty, respectively, whereas the luminal area was 5.5 +/- 1.2 versus 5.7 +/- 1.2 mm(2) and the plaque area was 8.5 +/- 2.7 versus 9.1 +/- 2.2 mm(2), respectively. The vessel area was smaller and the plaque area significantly smaller after CBA. Vessel expansion accounted for 45% of luminal enlargement, and plaque compression or shift accounted for 55% after CBA. After conventional angioplasty, vessel expansion accounted for 67%, and plaque compression or shift for 33% of luminal enlargement. The vessel expansion ratio was significantly smaller after CBA than after conventional angioplasty (1.05 vs 1.22, p <0.05). These findings suggest that the predominant mechanism of dilatation after CBA is plaque compression or shift rather than vessel expansion, unlike conventional angioplasty.

Angioplasty, Balloon, Coronary↗

A case of acute myocardial infarction treated with a new thrombectomy system.

Thrombotic occlusion in the culprit lesion of acute myocardial infarction was successfully recanalized using a 4.5 Fr thrombectomy catheter (RESCUE), which was also used to normalize the coronary blood flow. The retrieved specimens were white thrombi containing red thrombi and cholesterol crystals, indicating plaque rupture.

Adult↗

Fos expression in GABAergic cells and cells immunopositive for NMDA receptors in the inferior and superior colliculi following audiogenic seizures in rats.

Given the evidence that the inferior colliculus (IC) and superior colliculus (SC) seem to play key roles in connecting auditory pathways and seizure output pathways in the neuronal network for audiogenic seizures (AS) in rats, we examined Fos activation in GABAergic cells and cells immunopositive for glutamate N-methyl-D-aspartate (NMDA) receptors in the IC and SC following AS using the double-labeling procedure. Generalized tonic-clonic seizures (GTCS), which developed as an advanced form of AS in some of the susceptible rats, induced an increase in Fos expression in three IC substructures-the dorsal cortex of IC (DCIC), central nucleus of IC (CIC), and external cortex of IC (ECIC)-and in one SC substructure, the deep gray layer of SC (DpG). Compared with the rats showing GTCS, rats exhibiting wild running (WR) without proceeding to GTCS showed a different pattern of AS-induced Fos expression. The DpG in the WR animals showed no significant increase in the levels of Fos-like immunoreactivity. The degrees of Fos activation that occurred in GABAergic cells and cells immunopositive for NMDA receptors were similar in the DCIC, CIC, ECIC, and DpG following AS. These results suggest that Fos activation in the DpG is involved in the development from WR to GTCS in AS-susceptible rats. They also provide some evidence that some GABAergic neurons in the IC and SC and glutamatergic afferents (via NMDA receptors) to these structures are activated by AS.

Acoustic Stimulation↗

Interleukin-1-induced glenohumeral synovitis and shoulder pain in rotator cuff diseases.

Synovitis of the subacromial bursa has been identified as a main source of shoulder pain in rotator cuff diseases. Little interest, however, has been paid into the synovitis of glenohumeral joint. The mRNA expression levels of interleukin-1beta (IL-1beta) and interleukin-1 receptor antagonists produced in the synovitis reflect the magnitude of inflammation. The present study was undertaken to determine the relationship between mRNA expression levels of IL-1beta and its receptor antagonists (secreted interleukin-1 receptor antagonist (IL-1ra) and intracellular IL-1ra) in the synovium of the glenohumeral joint and shoulder pain in rotator cuff diseases, analyzing the synovial specimens by reverse transcriptase polymerase chain reaction. Thirty-five patients with rotator cuff diseases were candidates. Based on the presence of cuff perforation, they were divided into two categories: 16 with non-perforating tears and 19 with perforating tears. The degree of shoulder pain was evaluated by use of a visual analogue scale. The pain degree of non-perforating tears was significantly greater than that of perforating tears (P < 0.01). In contrast, the expression levels of the cytokine-mRNAs were constitutively greater in perforating tears than in non-perforating tears (P < 0.01, respectively). The expression levels of the cytokine-mRNAs were inversely correlated with the degree of pain (IL-1beta: r = 0.930; secreted IL-1ra: r = 0.861; intracellular IL-1ra: r = 0.932, P < 0.001 respectively). These results suggest that the expression levels of the cytokine-mRNAs in the synovium of the glenohumeral joint contribute less to the generation of shoulder pain in rotator cuff diseases.

Adult↗

Randomized trial of trigger point injection for renal colic.

BACKGROUND: Many drugs have been utilized for the treatment of renal colic, but to date no drugs that relieve pain quickly and completely have been developed. Thus, we conducted a prospective trial to evaluate the effects of trigger point injection on renal colic. In this study, we used a local injection of lidocaine to the trigger point of patients experiencing renal colic, and evaluated the efficacy in patients using the visual analog scale. METHODS: Sixty patients with renal colic were enrolled in this study and divided into two groups by a simple randomization: (i) the butylscopolamine group (n = 30, intravenous injection of butylscopolamine bromide and sulpyrine); and (ii) the lidocaine group (n = 30, local anesthesia to the trigger point with lidocaine). RESULTS: Renal colic had disappeared completely at the end of the trigger point injection in 15/30 patients and the average time required to produce a 50% improvement in symptoms was 9 min in all patients in the group. In the lidocaine group, only one patient needed an additional anodyne treatment after 60 min and none of the 29 patients whose pain disappeared within 60 min needed further anodyne treatment within 24 h. These results were all significantly superior to those of the conventional treatment. No side-effects and complications were observed. CONCLUSION: Trigger point injection, in our experience, is an easy, safe and effective method for the amelioration of renal colic. It was significantly superior to the combination of intravenous butylscopolamine and sulpyrine.

Adult↗

Favourable long-term outcome by repeated percutaneous coronary revascularization in diabetic haemodialysis patients.

BACKGROUND: Diabetic haemodialysis patients have a high prevalence of coronary events and very high mortality rates. Percutaneous coronary intervention has become a well-established and routine procedure for coronary revascularization. This study investigated the long-term outcome of multiple repeated interventions in diabetic haemodialysis patients with coronary artery disease. METHODS: A retrospective study compared 37 type II diabetic haemodialysis patients with coronary artery disease and 26 non-diabetic patients matched for age, angiographic morphology, and devices of percutaneous intervention. All patients had undergone successful percutaneous intervention prior to enrollment. Percutaneous interventions were repeated in the event of restenosis or the development of a de novo lesion. RESULTS: Diabetic and non-diabetic patients were similar in terms of the number of follow-up angiograms (2.3+/-1.6 vs 2.4+/-1.5/patient) and interventions (2.2+/-1.4 vs 2.2+/-1.5/patient), incidence of target lesion revascularization (85 vs 82%), and number of de novo lesions (15 vs 17%). The cumulative survival rates after the initial percutaneous intervention were similar in the groups (42% vs 31% at 80 months). Cardiac death occurred in 33% of diabetic patients and 42% of non-diabetic patients. Repeated intervention (regression coefficient=16.0, P<0.001) and a lower left ventricular ejection fraction (regression coefficient=-12.9, P=0.047) were determined for the important clinical factors associated with the survival duration after initial coronary intervention. CONCLUSIONS: Multiple repeated percutaneous interventions reduce the long-term mortality of diabetic and non-diabetic haemodialysis patients with coronary artery disease similarly. Multiple repeated percutaneous coronary interventions are a viable option for controlling myocardial ischaemia and improving the long-term outcome in high-risk diabetic haemodialysis patients.

Aged↗

Coronary disease morphology and distribution determined by quantitative angiography and intravascular ultrasound--re-evaluation in a cooperative multicenter intravascular ultrasound study (COMIUS).

Although previous studies have demonstrated that even quantitative coronary angiography (QCA) can not provide accurate disease morphology, there has not been a systematic comparison of disease morphology determined by QCA and intravascular ultrasound (IVUS), particularly in Japanese patients. Therefore, the present study prospectively examined patients in a multicenter cooperative study. A total of 491 coronary sites from 562 patients (446 men, 116 women; mean age, 64+/-11 years) who underwent coronary interventions were enrolled. The target lesions (>50% diameter stenosis) were evaluated pre-operatively by both QCA and IVUS operating at 30-40 MHz and the percent area stenosis, eccentricity index (EI) and lesion length were determined. The minimal (min) and maximal (max) distances from the center of the stenotic lesion to the outline of the vessel wall were measured, and the EI was calculated by the formula: [(max - min)/max]. By QCA, lesion length was determined by measuring the distance between the proximal and distal shoulders of the lesion. When the lesions were observed by IVUS with a motorized pull-back system, the length was calculated by multiplying the time for observation of the disease and 0.5 or 1 mm/s. Although the severity of the stenosis determined by QCA (86+/-10%, mean +/- SD) did not differ from that by IVUS (83+/-13%), there was no correlation between them (r=0.32, y=0.25x+65) and the correlation did not improve when lesions with remodeling, enlargement (n=176) or shrinkage (n=79) were omitted from the calculation. The EIs by QCA and IVUS were 0.51+/-0.26 and 0.52+/-0.22, respectively (NS), and there was no correlation between them (r=0.30, y=0.36x+33). However, when the lesions with remodeling were excluded, the correlation greatly improved (r=0.80, y=0.84x+10.6, p<0.05). Lesion length determined by QCA (12.4+/-6.1 mm) was significantly shorter than that by IVUS (16.3+/-8.9 mm, p<0.01). These results demonstrate that coronary angiography significantly misinterprets disease morphology in terms of severity, eccentricity and length, in part because of vessel remodeling that can be accurately determined only by IVUS.

Aged↗

Human thrombospondin 2 inhibits proliferation of microvascular endothelial cells.

This study was performed to characterize human thrombospondin 2 (TSP2). TSP2 has recently attracted attention as an endogenous negative regulator of angiogenesis in tumorigenesis. We cloned and transfected human TSP2 cDNA into the human colon cancer cell line SW-480. Stable transfectants (TSP2-1, TSP2-6) overexpressing TSP2 were established. Growth characteristics of TSP2-transfectants were investigated in vitro and in vivo. TSP2-transfectants showed similar growth properties to vector-transfectants and wild-type SW-480 cells. The overexpression of transfected human TSP2 cDNA did not affect proliferation of SW-480 cells. When the conditioned media of TSP2-transfectants were added to cultures of bovine pulmonary microvascular endothelial cells (BPMEC), the BPMEC proliferation was significantly inhibited. These results suggested that human TSP2 is a potential inhibitor of angiogenesis.

Angiogenesis Inhibitors↗

Expression of interleukin-10 is inversely correlated with distant metastasis of renal cell carcinoma.

Interleukin-10 (IL-10) is an immunomodulative cytokine produced by T cells, B cells, and monocytic cells. The significance of IL-10 and IL-10R expression in renal cell carcinoma (RCC) has not been well characterized. In this study, we assessed the correlation between IL-10 gene expression and its pathological significance in 44 RCC specimens. The patients with IL-10 gene expression showed a decreased incidence of metastasis compared to those without IL-10 gene expression. The expression of IL-10 was correlated with vascular endothelial growth factor (VEGF)-A gene expression. These findings suggest that IL-10 gene expression plays some roles in the metastasis of RCC.

Angiopoietin-2↗

[Hypertrophic cardiomyopathy with mid-ventricular obstruction complicated with apical left ventricular aneurysm and ventricular tachycardia: a case report].

A 69-year-old man was admitted with palpitations and syncope. His medical history included hypertension and left ventricular hypertrophy. Arterial pulsation was not palpable on admission. Electrocardiography revealed ventricular tachycardia, and cardioversion restored normal sinus rhythm. An electrophysiological study reproducibly induced polymorphic ventricular tachycardia, so a cardioverter defibrillator was implanted. Echocardiography revealed mid-ventricular obstruction and an apical aneurysm, and Doppler color flow imaging showed a diastolic paradoxic jet from the apex toward the base. Coronary angiography showed no stenosis of the extramural coronary arteries. Ventricular tachycardia on admission showed a right bundle branch block pattern and a superior axis deviation, so the arrhythmia was thought to originate from the apical aneurysm. Apical aneurysm can result from elevated intraventricular pressure or relative myocardial ischemia. This is a rare case of hypertrophic cardiomyopathy with mid-ventricular obstruction complicated with apical aneurysm and polymorphic ventricular tachycardia.

Aged↗

Ribozyme mediated suppression of vascular endothelial growth factor gene expression enhances matrix metalloproteinase 1 expression in a human hepatocellular carcinoma cell line.

The levels of expression of various genes were altered in cellular transformants with manipulation of expression of single genes. Vascular endothelial growth factor A (VEGF-A) is a key molecule for tumor progression, although it is unclear how VEGF-A expression regulates various genes. Multiple gene expression levels were evaluated using cDNA arrays in a human hepatocellular carcinoma cell line (HLF) with suppression of the VEGF-A gene by anti-VEGF-A ribozyme (alphaVRz). The ribozyme-mediated suppression of VEGF-A gene solely up-regulated matrix metalloproteinase 1 (MMP1) gene level in HLF/alphaVRz. Levels of expression of other members of MMP family or tissue inhibitors of MMPs did not show any alteration. These results suggested that intracellular suppression of VEGF-A gene was specifically linked to up-regulation of MMP1 in human hepatocellular carcinoma cells.

Carcinoma, Hepatocellular↗

Correlation between interleukin 10 and vascular endothelial growth factor expression in human esophageal cancer.

Interleukin 10 (IL-10) is an immunosuppressive cytokine produced by T-lymphocytes, and is a regulatory molecule for angiogenesis in various cancers. We examined IL-10 and vascular endothelial growth factor (VEGF) gene expression in 45 esophageal cancer patients who underwent surgical resection. Thirty-seven (82.2%) of the 45 esophageal cancers revealed IL-10 gene expression. VEGF121, VEGF165 and VEGF189 isoforms were detected in 93.3% (42/45), 55.6% (25/45) and 26.7% (12/45) of cases, respectively. IL-10 gene expression was significantly correlated with VEGF121 gene expression (P=0.0039, Fisher's test). The results suggested that IL-10 stimulates angiogenic factor gene expression.

Alternative Splicing↗

[A case of gastric cancer with paraaortic lymph node metastasis responding to TS-1/CDDP as neoadjuvant chemotherapy].

A 64-year-old male visited our hospital with complaints of epigastric pain. Computed tomography (CT) showed gastric cancer with extensive paraaortic lymph node metastasis. We decided that a curative operation was impossible, and administered the following chemotherapy. After 120 mg/day of TS-1 was orally administered for 3 weeks followed by 2 drug-free weeks with 90 mg of CDDP was administered intravenously on day 8, CT showed a 90.6% reduction in the paraaortic lymph node metastasis. No serious adverse reaction was observed. After 2 courses of this chemotherapy, surgery was performed after informed consent was obtained from the patient. Histrogical result showed PR. The patient is now healthy and no sign of recurrence has been observed. TS-1/CDDP therapy is useful for advanced gastric cancer.

Adenocarcinoma↗

Angiopoietin-1 and vascular endothelial growth factor expression in human esophageal cancer.

Angiopoietin-1 (Ang-1) has been shown to act as an angiogenic promoter in embryonic angiogenesis by promoting vascular branching, pericyte recruitment and endothelial survival. Ang-1 expression has not been examined in human esophageal cancer. We examined Ang-1 and vascular endothelial growth factor (VEGF) gene expression in tumors from 45 esophageal cancer patients who underwent surgical resection. Forty (88.9%) of the 45 esophageal cancers revealed Ang-1 gene expression. VEGF121, VEGF165 and VEGF189 isoforms were detected in 93.3 (42/45), 55.6 (25/45) and 26.7% (12/45) of the cases, respectively. Ang-1 gene expression was significantly correlated with VEGF121 and VEGF165 gene expression (P=0.0289 and P=0.0127, respectively, Fisher's test). The results suggest that Ang-1 is associated with neovascularization in the cancer stroma through VEGF net-works in esophageal cancer.

Angiogenesis Inducing Agents↗

Reversal of drug resistance using hammerhead ribozymes against multidrug resistance-associated protein and multidrug resistance 1 gene.

We examined the effects of suppressing multidrug resistance-associated protein (MRP) and multidrug resistance 1 (MDR1) gene expression in HCT-8DDP human colon cancer cell lines, which showed both cisplatin and multidrug resistance. Hammerhead ribozymes, designed to cleave MRP mRNA (anti-MRP Rz) and MDR1 mRNA (anti-MDR1 Rz), were transfected into the HCT-8DDP cells. Drug sensitivity was estimated by MTT assay in vitro. The HCT-8DDP/anti-MRP Rz cells were more sensitive to doxorubicin (DOX) and etoposide (VP-16) by 2.5- and 4.1-fold, respectively, compared with HCT-8DDP cells. The HCT-8DDP/anti-MDR Rz cells were more sensitive to DOX and VP-16 by 2.3- and 3.8-fold, respectively. The anti-MRP Rz and anti-MDR1 Rz significantly down-regulated resistance to DOX and VP-16, while anti-MRP Rz and anti-MDR1 Rz did not affect resistance to cisplatin, methotrexate and 5-fluorouracil. The hammerhead ribozyme-mediated specific suppression of MRP or MDR1 was sufficient to reverse multidrug resistance in the human colon cancer cell line.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Ribozyme mediated cleavage of cell-associated isoform of vascular endothelial growth factor inhibits liver metastasis of a pancreatic cancer cell line.

Stromal angiogenesis is an important factor for progression of malignant neoplasms. We used hammerhead ribozymes against vascular endothelial growth factor (VEGF) gene transcripts to down-regulate cell-associated VEGF189 isoform function in the pancreatic cancer cell line MIA PaCa2. MIA PaCa2 transfected with anti-VEGF189 ribozyme did not show any alteration of growth rate under tissue culture. When the transformants were subcutaneously transplanted, tumour volume of the ribozyme-transfected MIA PaCa2 xenografts was significantly smaller (P<0.01). No metastasis of MIA PaCa2 transfected with anti-VEGF189 was apparent, while disabled ribozyme-transfected MIA PaCa2 showed significant liver metastasis (P<0.05). These results suggested that VEGF189 plays an important role in growth and metastatic potential through alteration of angiogenic balance in cancer.

Animals↗

[TS-1/CDDP therapy for advanced gastric cancer as neoadjuvant chemotherapy].

Five patients with inoperable advanced gastric cancer were treated with combination chemotherapy of TS-1 and cisplatin (CDDP). TS-1 of 80-120 mg/body/day was orally administered for 3 weeks followed by 2 drug-free weeks, and 60 mg/m2/day of CDDP was venally administered on Day 8. It was possible to evaluate all 5 patients for response and toxicity. Only low grade toxicities (Grade 1 or 2) of leukocytopenia, neutrocytopenia, anemia, nausea, diarrhea and stomatitis were seen. Four of 5 patients achieved a partial response, for a response rate of 80.0%. Stomach, liver, lymph node and peritoneal tumors responded to TS-1/CDDP. TS-1/CDDP therapy produces a high response in cases of gastric cancer, and it is useful as a neoadjuvant chemotherapy.

Aged↗

Unique properties of 189 amino acid isoform of vascular endothelial growth factor in tumorigenesis.

The 189 amino acid isoform of vascular endothelial growth factor (VEGF189) has been shown to be more strongly associated with the cell membrane than other isoforms of human VEGF (VEGF121, VEGF165). To analyze the biological activities of these VEGF isoforms on tumor growth, we transfected human VEGF121, VEGF165 or VEGF189 cDNA into the human colon cancer cell line SW-480, and established several clones overexpressing these VEGF isoforms. The total amounts of VEGF protein in the culture supernatants of the VEGF189-transfectants were less than those of VEGF121 and VEGF165-transfectants. These transfectants showed no significant differences in growth in culture. Nevertheless, the rate of in vivo tumor growth of VEGF189-transfectants was faster than or equivalent to that of VEGF121-transfectants, while the VEGF165-transfectant showed the greatest enhancement of tumor growth. The protein levels of VEGF were markedly increased only in the VEGF189-transfectants cultured in the presence of heparin. The enhanced in vivo tumor growth of VEGF189-transfectants can be partly explained by the cell-associated features of VEGF189 molecules. The VEGF189 molecule, which is strongly bound to the cell surface, has unique properties and high potential in local angiogenesis and tumor growth in the cancer inductive microenvironment.

Animals↗