Biomedical subjects

M Minami

Publications and source records attributed to M Minami.

At least 55 records · Page 3Linked to original sources

PubMed2001

Single lung transplantation from a brain-dead donor for a patient with idiopathic pulmonary fibrosis. A breakthrough after new legislation in Japan.

Two single lung transplants from a single cadaveric donor were successfully conducted at 2 institutions on March 29, 2000, the first such procedure in Japan under newly introduced legislation. Our patient was a 48-year-old woman with idiopathic pulmonary fibrosis who underwent left single-lung transplantation under cardiopulmonary support. The donor lung was preserved in 4 degrees C modified Euro-Collins solution. Total ischemic time was 5 hours and 37 minutes. The postoperative course was uneventful. The patient was discharged on postoperative day 62 with satisfactory respiratory function.

Brain Death↗

PubMed2001

An analysis of video-assisted thoracoscopic resection for mediastinal masses in 150 cases. An overview of the pansternal approach, histology, and complications.

BACKGROUND: To clarify the usefulness of the diagnosis and treatment of mediastinal masses, by video-assisted thoracoscopic surgery (VATS), we performed a retrospective multi-institutional study to delineate the type of approach, histopathology, and complications associated with these entities. METHODS: We analyzed 150 patients who underwent the VATS procedure at several institutions between 1991 and 1999. RESULTS: VATS resections were performed using various combinations of the "pansternal approach." The unilateral thorax approach was applied in 135 patients, the bilateral thorax approach combined with the suprasternum approach in seven patients, the unilateral thoracic approach combined with the supraclavicular approach in three patients, the infrasternal approach in three patients, and the bilateral thoracic approach combined with both the infrasternal and the suprasternal approaches in two patients. Thoracoscopic resections or biopsies diagnosed 140 benign and 10 malignant mediastinal masses. There were operative complications in nine patients (6%). Eight patients (5.3%) were converted to conventional thoracotomy. CONCLUSION: VATS is a safe, effective, minimally invasive technique that can facilitate the resection of mediastinal masses when the pansternal approach is applied as appropriate for the location of the tumor.

Adolescent↗

PubMed2001

VCAM-1 expression precedes macrophage infiltration into subendothelium of vein grafts interposed into carotid arteries in hypercholesterolemic rabbits--a potential role in vein graft atherosclerosis.

Intimal hyperplasia and atherosclerosis are major causes of late vein graft failure after coronary artery bypass surgery. Hypercholesterolemia appears to be a key risk factor for atherosclerosis in vein grafts as well as in native arteries. We used a rabbit model of interposition jugular vein graft to the carotid artery and compared intimal thickening, macrophage accumulation, and VCAM-1 expression between hypercholesterolemic (H group) and normocholesterolemic (N group) rabbits. Fifty-nine rabbits were divided into H and N groups. Intimal thickening in vein grafts was approximately three times more prominent in the H group than in the N group. Macrophage accumulation progressively increased with time in H group vein grafts, although it was negligible in the N group. In the H group, moreover, macrophages were initially more abundant in deep intima, and subsequently accumulated in subendothelium of the grafted vein. VCAM-1 expression in luminal endothelial cells of the grafted veins was time-dependently increased after the vein graft surgery in both the H and N groups, and was more prominent in the H group. Comparison of the time-courses between macrophage accumulation and VCAM-1 expression revealed that VCAM-1 expression in luminal endothelium preceded subendothelial accumulation of macrophages. VCAM-1 expression and macrophage accumulation may be key factors which regulate progression of vein graft atherosclerosis.

Animals↗

PubMed2001

Germline mutations of the PTCH gene in Japanese patients with nevoid basal cell carcinoma syndrome.

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental and skeletal anomalies, palmo-plantar pits, odontogenic keratocysts, ectopic calcification, and occurrence of various types of tumors including basal cell carcinoma. Recent evidence has indicated that the human homologue of a Drosophila segment polarity gene, PTCH, is a NBCCS susceptibility gene. In the study presented here, we detected two novel mutations of the PTCH gene, I805X/2395delC and Y93X/C297A, in two unrelated Japanese patients. Early protection of the skin from the sunlight is important to the prevention of BCC development in NBCCS patients. Genetic analysis of the PTCH gene is essential for the early, definitive diagnosis of NBCCS, especially before the expression of clinical manifestations is complete.

Adult↗

PubMed2001

Retreatment with interferon-alpha at dosages or period increased by 1.3 times is effective for treatment for transient responders and non-responders in chronic hepatitis C patients.

The objectives of retreatment with interferon (IFN) in chronic hepatitis C (CH-C) patients are sustained response and a reduction in the risk of hepatocellular carcinoma (HCC). However, it is still unclear, as to which patients are candidates for retreatment with IFN. Eighteen transient responders (TRs) and 15 non-responders (NRs) to IFN therapy in CH-C received retreatment with IFNalpha. Of the 18 TRs, five showed sustained disappearance of hepatitis C virus, two showed sustained biochemical response, 10 continued as TR and one was a NR. Of the 15 NRs, six showed a TR while nine continued as NRs. Responsive cases, which included the virologically or biochemically sustained and transient responders, received either a dose of IFN 1.3 times greater or were treated for a period of 1.3 times longer in the retreatment than the original treatment. We submit that IFN treatment consisting of either a time period or a dosage 1.3 times those of the original IFN administration may be beneficial in the case of TR and NR in chronic hepatitis C patients.

Journal Article↗

PubMed2001

Both the N- and C-terminal chaperone sites of Hsp90 participate in protein refolding.

Hsp90 is able to bind partially unfolded firefly luciferase and maintain it in a refoldable state; the subsequent successive action of the 20S proteasome activator PA28, Hsc70 and Hsp40 enables its refolding. Hsp90 possesses two chaperone sites in the N- and C-terminal domains that prevent the aggregation of denatured proteins. Here we show that both chaperone sites of Hsp90 are effective not only in capturing thermally denatured luciferase, but also in holding it in a state prerequisite for the successful refolding process mediated by PA28, Hsc70 and Hsp40. In contrast, the heat-induced activity of Hsp90 to bind chemically denature dihydrofolate reductase efficiently and prevent its rapid spontaneous refolding was detected in the N-terminal site of Hsp90 only, while the C-terminal site was without effect. Thus it is most likely that both the N- and C-terminal chaperone sites may contribute to Hsp90 function as holder chaperones, however, in a significantly distinct manner.

Animals↗

PubMed2001

Extensive mesenteric vein and portal vein thrombosis successfully treated by thrombolysis and anticoagulation.

Mesenteric vein thrombosis is generally difficult to diagnose and can be fatal. A case of extensive thrombosis of the mesenteric and portal veins was diagnosed early and successfully treated in a 26-year-old man with Down syndrome who was admitted to hospital because of abdominal pain, severe nausea and high fever. Ultrasonography revealed moderate ascites, and there was minimal flow in the portal vein (PV) on the Doppler examination. Computed tomography (CT) showed remarkable thickening of the walls of the small intestine and extensive thrombosis of the mesenteric, portal and splenic veins. Because neither intestinal infarction nor peritonitis was seen, combined thrombolysis and anticoagulation therapy without surgical treatment was chosen. Urokinase was administered intravenously and later through a catheter in the superior mesenteric artery. Heparin and antibiotics were given concomitantly. The patient's symptoms and clinical data improved gradually. After 10 days, CT revealed that collateral veins had developed and the thrombi in the distal portions of the mesenteric veins had dissolved, although the main trunk of the PV had not recanalized. The only risk factor of thrombosis that was detected was decreased protein S activity.

Adult↗

PubMed2001

A prospective randomized study comparing volume-standardized modified and conventional ultrafiltration in pediatric cardiac surgery.

BACKGROUND: Modified ultrafiltration has been touted as superior to conventional ultrafiltration for attenuating the consequences of hemodilution after cardiac surgery with cardiopulmonary bypass in children. We conducted a prospective randomized study to test the hypothesis that modified and conventional ultrafiltration have similar clinical effects when a standardized volume of fluid is removed. METHODS: From October 1998 to September 1999, 110 children weighing 15 kg or less (median weight 6.1 kg, median age 6.3 months) undergoing surgery with cardiopulmonary bypass for functionally biventricular congenital heart disease were randomized to conventional (n = 67) or arteriovenous modified ultrafiltration (n = 43) for hemoconcentration. The volume of fluid removed with both methods was standardized as a percentage of effective fluid balance (the sum of prime volume and volume added during cardiopulmonary bypass minus urine output): in patients weighing less than 10 kg, 50% of effective fluid balance was removed, whereas 60% was removed in patients weighing 10 to 15 kg. Hematocrit, hemodynamics, ventricular function, transfusion of blood products, and postoperative resource use were compared between groups. RESULTS: There were no significant differences between groups in age, weight, or duration of cardiopulmonary bypass. The total volume of fluid added in the prime and during bypass was greater in patients undergoing conventional ultrafiltration than in those receiving modified ultrafiltration (205 +/- 123 vs 162 +/- 74 mL/kg; P =.05), although the difference was due primarily to a greater indexed priming volume in patients having conventional ultrafiltration. There was no difference in the percentage of effective fluid balance that was removed in the 2 groups. Accordingly, the volume of ultrafiltrate was greater in patients receiving conventional than modified ultrafiltration (95 +/- 63 vs 68 +/- 28 mL/kg; P =.01). Preoperative and postoperative hematocrit levels were 35.6% +/- 6.6% and 36.3% +/- 5.6% in patients having conventional ultrafiltration and 34.4% +/- 6.7% and 38.7% +/- 7.5% in those having modified ultrafiltration. By repeated-measures analysis of variance, patients receiving modified and conventional ultrafiltration did not differ with respect to hematocrit value (P =.87), mean arterial pressure (P =.85), heart rate (P =.43), or left ventricular shortening fraction (P =.21) from baseline to the postbypass measurements. There were no differences between groups in duration of mechanical ventilation, stay in the intensive care unit, or hospitalization. CONCLUSIONS: When a standardized volume of fluid is removed, hematocrit, hemodynamics, ventricular function, requirement for blood products, and postoperative resource use do not differ between pediatric patients receiving conventional and modified ultrafiltration for hemoconcentration after cardiac surgery.

Blood Transfusion↗

PubMed2001

Antitumor bicyclic hexapeptide RA-VII modulates cyclin D1 protein level.

A bicyclic hexapeptide, RA-VII or O-methyl deoxybouvardin, isolated from Rubia cordifolia, is known to inhibit protein biosynthesis in vitro and in vivo. We here demonstrate that the treatment of human colon cancer DLD-1 cells with RA-VII induces cell growth inhibition associated with a partial G1 arrest and a rapid decrease (below 2 h) in the level of cyclin D1 protein. Since cycloheximide, another protein synthesis inhibitor, neither decreased the amount of cyclin D1 in the cells nor arrested cells in G1 phase, it is unlikely that this RA-VII-induced reduction of cyclin D1 was fully dependent on its direct inhibitory effect of protein synthesis. Northern blot analysis revealed that RA-VII did not affect the level of cyclin D1 mRNA. Meanwhile, pre-treatment of cells with lactacystin, a proteasome inhibitor, abolished the RA-VII-induced decrease in cyclin D1. Moreover, RA-VII still decreased cyclin D1 protein in the presence of cycloheximide. These results indicate that the RA-VII-induced cyclin D1 decrease depends on cyclin D1 degradation via the ubiquitin-proteasome pathway and does not require additional protein synthesis. RA-VII might actively proceed the degradation process of cyclin D1 via the ubiquitin-proteasome pathway in DLD-1 cells.

Acetylcysteine↗

PubMed2001

Intracellular Bax translocation after transient cerebral ischemia: implications for a role of the mitochondrial apoptotic signaling pathway in ischemic neuronal death.

Activation of terminal caspases such as caspase-3 plays an important role in the execution of neuronal cell death after transient cerebral ischemia. Although the precise mechanism by which terminal caspases are activated in ischemic neurons remains elusive, recent studies have postulated that the mitochondrial cell death-signaling pathway may participate in this process. The bcl-2 family member protein Bax is a potent proapoptotic molecule that, on translocation from cytosol to mitochondria, triggers the activation of terminal caspases by increasing mitochondrial membrane permeability and resulting in the release of apoptosis-promoting factors, including cytochrome c. In the present study, the role of intracellular Bax translocation in ischemic brain injury was investigated in a rat model of transient focal ischemia (30 minutes) and reperfusion (1 to 72 hours). Immunochemical studies revealed that transient ischemia induced a rapid translocation of Bax from cytosol to mitochondria in caudate neurons, with a temporal profile and regional distribution coinciding with the mitochondrial release of cytochrome c and caspase-9. Further, in postischemic caudate putamen in vivo and in isolated brain mitochondria in vitro, the authors found enhanced heterodimerization between Bax and the mitochondrial membrane permeabilization-related proteins adenine nucleotide translocator (ANT) and voltage-dependent anion channel. The ANT inhibitor bongkrekic acid prevented Bax and ANT interactions and inhibited Bax-triggered caspase-9 release from isolated brain mitochondria in vitro. Bongkrekic acid also offered significant neuroprotection against ischemia-induced caspase-3 and caspase-9 activation and cell death in the brain. These results strongly suggest that the Bax-mediated mitochondrial apoptotic signaling pathway may play an important role in ischemic neuronal injury.

Animals↗

PubMed2001

Global ischemia induces expression of acid-sensing ion channel 2a in rat brain.

Acid-sensing ion channels (ASICs) are ligand-gated cation channels that respond to acidic stimuli. They are expressed throughout the mammalian nervous system. In the peripheral nervous system, ASICs act as nociceptors, responding to the tissue acidosis that accompanies ischemic and inflammatory conditions. The function of ASICs in the central nervous system is not known. In this article, the authors present evidence that transient global ischemia induces ASIC 2a protein expression in neurons that survive ischemia. Western blot analysis with an anti-ASIC 2a antibody revealed up-regulation of an 80 kD protein in ischemic rat brain. Immunohistochemical analysis showed that ASIC 2a protein expression increased in neurons of the hippocampus and cortex. Klenow fragment-mediated labeling of DNA strand breaks determined that ASIC 2a induction did not occur in cells with detectable DNA damage. The current results suggest a possible role for ASICs in mediating a cellular response to ischemia.

Acid Sensing Ion Channels↗

PubMed2001

Chemokine receptor antagonist peptide, viral MIP-II, protects the brain against focal cerebral ischemia in mice.

The authors previously reported that mRNA for macrophage inflammatory protein-1alpha (MIP-1 alpha), a member of the CC chemokines, was expressed in glial cells after focal cerebral ischemia in rats. However, the function of chemokines in the ischemic brain remains unclear. Recently, viral macrophage inflammatory protein-II (vMIP-II), a chemokine analogue encoded by human herpesvirus-8 DNA, has been demonstrated to have antagonistic activity at several chemokine receptors. In the present study, the effects of vMIP-II and MIP-1alpha on ischemic brain injury were examined in mice to elucidate the roles of chemokines endogenously produced in the ischemic brain. Intracerebroventricular injection of vMIP-II (0.01-1 microg) reduced infarct volume in a dose-dependent manner when examined 48 hours after 1-hour middle cerebral artery occlusion followed by reperfusion. However, 1 microg MIP-1alpha increased infarct volume in the cortical region. These results supported the possibility that chemokines endogenously produced in the brain are involved in ischemic injury, and that chemokine receptors are potential targets for therapeutic intervention of stroke.

Animals↗

PubMed2001

Role of oxidized LDL in atherosclerosis.

A critical event in the early stages of atherosclerosis is the focal accumulation of lipid-laden foam cells derived from macrophages. In various cholesterol-fed animal models of atherosclerosis, localized attachment of circulating monocytes to arterial endothelial cells appeared to precede the formation of foam cells. It is suggested that monocyte recruitment into early lesions depends on the endothelial adhesiveness for monocytes and lymphocytes. In vivo and in vitro experiments have identified molecules, such as ICAM-1, VCAM-1, and P-selectin, that can support the adhesion of monocytes and lymphocytes. Moreover, oxidized LDL, lysophosphatidyl-choline, and oxidized fatty acids induce the expression not only of these adhesion molecules but also of scavenger receptors, such as CD-36, SR-A, and LOX-1. Recently, we isolated and characterized the novel receptors for oxidized LDL, namely, LOX-1 and SR-PSOX. Expression of LOX-1 is found on endothelial cells, smooth muscle cells, and macrophages, whereas SR-PSOX is expressed on macrophages. In this paper the significance of oxidized LDL and its receptors, LOX-1 and SR-PSOX, in terms of atherogenesis is discussed.

Animals↗

PubMed2001

Peroxisome proliferator-activated receptor a ligands increase lectin-like oxidized low density lipoprotein receptor-1 expression in vascular endothelial cells.

Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is a receptor for atherogenic oxidized LDL expressed in vascular endothelial cells, smooth muscle cells, and macrophages. Peroxiosme proliferator-activated receptors (PPARs) include subfamilies PPARalpha and PPARgamma, which are expressed in endothelial cells and involved in transcriptional regulation of a large number of genes that affect lipoprotein and fatty acid metabolism as well as inflammation. We therefore explored the effects of PPARalpha and PPARgamma ligands on expression of LOX-1. Treatment of cultured bovine aortic endothelial cells (BAECs) with PPARalpha ligands (fenofibrate and WY14643) remarkably upregulated LOX-1 expression, which was detected by western and northern blot analyses. LOX-1 promoter-reporter gene assay showed that PPARalpha ligands activate transcription of the LOX-1 gene. PPARgamma ligands, in contrast, did not significantly affect LOX-1 expression in BAECs. PPARalpha appears to be a key regulator in promoting LOX-1 expression in BAECs. Upregulated expression of LOX-1 may modulate the catabolism of oxidized LDL and atherosclerotic progression.

Animals↗

PubMed2001

Expression of scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX) in human atheroma.

Recently, we identified a novel macrophage cell-surface receptor for oxidized low-density lipoprotein (Ox-LDL), designated SR-PSOX (scavenger receptor for phosphatidylserine and oxidized lipoprotein). Here we examine SR-PSOX expression in human atherosclerotic lesions using carotid endarterectomy specimens from 21 patients, directional coronary atherectomy specimens from 11 patients, and normal aortas from 2 patients. RT-PCR analysis demonstrated that SR-PSOX expression was upregulated in atherosclerotic lesions, but undetectable in normal aortas. Immunohistochemistry showed that SR-PSOX was abundantly expressed by macrophages in the intima of atherosclerotic lesions. Taken together, SR-PSOX may be involved in Ox-LDL uptake and subsequent foam cell transformation in macrophages in vivo and therefore may play important roles in human atherosclerotic lesion formation.

Arteriosclerosis↗

PubMed2001

Immune response induced by airway sensitization after influenza A virus infection depends on timing of antigen exposure in mice.

To study which phase of viral infection promotes antigen sensitization via the airway and which type of antigen-presenting cells contributes to antigen sensitization, BALB/c mice were sensitized by inhalation of ovalbumin (OA) during the acute phase or the recovery phase of influenza A virus infection, and then 3 weeks later animals were challenged with OA. The numbers of eosinophils and lymphocytes, the amounts of interleukin-4 (IL-4) and IL-5 in the bronchoalveolar lavage fluid, and the serum levels of OA-specific immunoglobulin G1 (IgG1) and IgE increased in mice sensitized during the acute phase (acute phase group), while a high level of gamma interferon production was detected in those sensitized during the recovery phase (recovery phase group). In the acute phase group, both major histocompatibility complex class II molecules and CD11c were strongly stained on the bronchial epithelium; in the recovery phase group, however, neither molecule was detected. OA-capturing dendritic cells (DCs) migrated to the regional lymph nodes, and a small number of OA-capturing macrophages were also observed in the lymph nodes of the acute phase group. In the recovery group, however, no OA-capturing DCs were detected in either the lungs or the lymph nodes, while OA-capturing macrophages were observed in the lymph nodes. These results indicate that the timing of antigen sensitization after viral infection determines the type of immune response.

Animals↗

PubMed2001

Appropriate dosing of pilsicainide hydrochloride in patients on hemodialysis.

Appropriate dosing of pilsicainide hydrochloride, an anti-arrhythmic drug excreted via the kidney, was investigated in patients on dialysis. Ten chronic hemodialysis patients with coexisting severe palpitation of supraventricular premature contractions (SVPC) were treated with 25 mg of pilsicainide hydrochloride before dialysis. All of their plasma concentrations were maintained within the therapeutic range and their mean dialysis rate was 32%. After 2 weeks, 7 patients were followed with consecutive daily dose treatment. In 3 of them, the dosage was returned to the single pre-dialysis administration because of the elevated plasma concentration reaching the toxic range 1 month after the start of administration. The dose schedule was maintained, and plasma pilsicainide concentrations remained within the therapeutic range during the 6-month follow-up. No abnormal findings were found in any parameters of electrocardiography, echocardiography or biochemistry. The number of SVPC diminished > 90% compared to the pretreatment level.

Anti-Arrhythmia Agents↗

PubMed2001

Lysophosphatidylcholine induces early growth response factor-1 expression and activates the core promoter of PDGF-A chain in vascular endothelial cells.

Lysophosphatidylcholine (lyso-PC), a polar phospholipid that is increased in atherogenic lipoproteins and atherosclerotic lesions, has been shown to transcriptionally induce the expression of endothelial genes relevant to atherogenesis. In cultured bovine aortic endothelial cells (BAECs), we show that lyso-PC induces the expression of early growth response factor (Egr)-1 and thereby activates the proximal promoter of the platelet-derived growth factor (PDGF)-A chain located 55 to 71 bp upstream from the transcription start site, which has been shown to be crucial for PDGF-A chain expression induced by fluid shear stress and fibroblast growth factor-1. Northern blot analyses showed that lyso-PC (10 to 20 micromol/L) transiently (30 minutes to 1 hour) induced expression of Egr-1 mRNA. Induced expression of Egr-1 mRNA, which was associated with increased amounts of Egr-1 protein in nuclei, preceded PDGF-A chain mRNA induction in lyso-PC-activated BAECS: Nuclear runoff assay revealed that lyso-PC stimulates transcription of the Egr-1 gene. Transient transfection of the oligonucleotide corresponding to the proximal promoter of the PDGF-A chain (oligo A) linked to the luciferase reporter gene revealed that lyso-PC can activate the core promoter of the PDGF-A chain by 5-fold. Insertion of a guanine at 3 sites in the oligo A abolished the lyso-PC-induced increases in luciferase activities. Electrophoretic mobility shift assay with use of radiolabeled oligo A showed a lyso-PC-inducible shift band, which was suppressed by excess amounts of unlabeled oligo A or an anti-Egr-1 antibody. In addition, lyso-PC-induced Egr-1 expression was inhibited by PD98059, a specific inhibitor of mitogen-activated protein kinase kinase-1 (MEK1), suggesting that lyso-PC-induced expression of Egr-1 depends on the MEK1/extracellular signal-regulated kinase pathway. Taken together, transcriptional activation of Egr-1-dependent genes by this atherogenic lipid may be a key regulator of atherogenesis.

Animals↗