Biomedical subjects

Shinobu Nakamura

Publications and source records attributed to Shinobu Nakamura.

13 recordsLinked to original sources

PubMed2004

Can the life span of human marrow stromal cells be prolonged by bmi-1, E6, E7, and/or telomerase without affecting cardiomyogenic differentiation?

BACKGROUND: Cell transplantation has recently been challenged to improve cardiac function of severe heart failure. Human mesenchymal stem cells (hMSCs) are multipotent cells that can be isolated from adult marrow stroma, but because of their limited life span, it is difficult to study them further. To overcome this problem, we attempted to prolong the life span of hMSCs and investigate whether the hMSCs modified with cell-cycle-associated genes can differentiate into cardiomyocytes in vitro. METHODS: We attempted to prolong the life span of hMSCs by infecting retrovirus encoding bmi-1, human papillomavirus E6 and E7, and/or human telomerase reverse transcriptase genes. To determine whether the hMSCs with an extended life span could differentiate into cardiomyocytes, 5-azacytidine-treated hMSCs were co-cultured with fetal cardiomyocytes in vitro. RESULT: The established hMSCs proliferated over 150 population doublings. On day 3 of co-cultivation, the hMSCs became elongated, like myotubes, began spontaneously beating, and acquired automaticity. Their rhythm clearly differed from that of the surrounding fetal mouse cardiomyocytes. The number of beating cardiomyocytes increased until 3 weeks. hMSCs clearly exhibited differentiated cardiomyocyte phenotypes in vitro as revealed by immunocytochemistry, RT-PCR, and action potential recording. CONCLUSIONS: The life span of hMSCs was prolonged without interfering with cardiomyogenic differentiation. hMSCs with an extended life span can be used to produce a good experimental model of cardiac cell transplantation and may serve as a highly useful cell source for cardiomyocytic transplantation.

Action Potentials↗

PubMed2004

Clinical application of wave intensity for the treatment of essential hypertension.

Wave intensity analysis is a method of studying intravascular flow wave propagation, calculated as the product of the rate of change in pressure (d P/ t) and the rate of change in velocity (d U/d t). The typical pattern of wave intensity seen during the cardiac cycle has two dominant peaks. The larger first peak (FP) occurs during early systole when a forward traveling compression wave is generated by the left ventricle. The second smaller peak (SP) follows a period of relatively little net wave production during mid-systole. Wave reflection is seen as a small backward-traveling compression wave occurring just after the first peak of wave intensity (NP). In this study, we investigated the usefulness of parameters from the wave intensity for estimating the efficacy of the Alpha-1 blocker, doxazosin, to reduce blood pressure, by the reduction of peripheral vascular resistance. We examined 20 patients with essential hypertension. Patients were included if their diastolic blood pressure was >95 mmHg on at least three separate visits to the clinic. The study consisted of a 2-week baseline phase followed by a 2-4-week dose-adjusted phase with doxazosin. Treatment began with 1 mg/day doxazosin, and the dose was doubled fortnightly until the diastolic blood pressure was <90 mmHg. Blood-pressure measurements and side effects were recorded at intervals of 2 weeks. Before and after 4 weeks of stable treatment with doxazosin, a comprehensive clinical evaluation was given. Doxazosin reduced systolic and diastolic blood pressure. Both FP and SP increased and NP decreased. DeltaMBP (change in mean blood pressure) correlated well with NP before and after the antihypertensive therapy. The efficacy of doxazosin was confirmed by the decreased reflection wave of aortic flow from wave intensity analysis. Thus, patients with a significant reflection wave may be good candidates for antihypertensive treatment by a vasodilator, such as doxazosin.

Adrenergic alpha-Antagonists↗

PubMed2004

[Angiography].

The clinical usefulness of three dimensional images was widely recognized. The three dimensional digital subtraction angiography (3D-DSA) well demonstrated anatomical structures of cerebral arteries with high special resolution. This 3D observation allowed high quality planning for aneurysmal coil packing and neck clipping. Because of the bony structure and curvy arterial anatomy in the skull base region, 3D-CTA and MRA was sometimes distureved the demonstration of the anatomical relationship adjacent to the aneurysm. However, 3D-DSA not only demonstrated arterial anatomy, but also analyzed of vascular structure, quantifiably. And it was useful in radiation dose reduction by reduction of DSA exposure number. We believe that 3D-DSA should provided useful information for planning of surgical and endovascular treatment in the field of cerebro-vascular disease.

Angiography, Digital Subtraction↗

PubMed2004

Production of IL-12, IL-18 and TNF-alpha by alveolar macrophages in hypersensitivity pneumonitis.

BACKGROUND AND AIM OF THE WORK: Hypersensitivity pneumonitis (HP) is characterized by a macrophage-lymphocyte alveolitis and granuloma formation. A wide range of cytokines have been implicated in the pathophysiology and development of granulomas in HP, but there is no information about the production of interleukin-12 (IL-12) and IL-18 by alveolar macrophages (AM) in human HP. We evaluated whether the production of IL-12, IL-18 and tumor necrosis factor-alpha (TNF-alpha) is locally increased in HP, and whether there is a correlation between these cytokines, as well as with the cellular profile of bronchoalveolar lavage (BAL) fluid in HP. METHODS: AM from 11 patients with HP and 10 control subjects were cultured for 24h in 10% RPMI medium alone, or with RPMI medium and lipopolysaccharide (LPS) (100 ng/ml). Cytokines in the culture supernatants were assayed by ELISA. RESULTS: The production of IL-18 and TNFalpha was increased in patients with HP in either absence or presence of LPS compared with controls. Although the spontaneous production of IL-12 was low, with LPS stimulation it was significantly elevated in HP. The concentration of the LPS-stimulated IL-12 production positively correlated with the percentage of lymphocytes (r = 0.72, p = 0.011), and negatively correlated with the percentage of macrophages (r = -0.88, p < 0.001). CONCLUSIONS: These observations suggest that IL-12, IL-18 and TNFalpha may be involved in the pathogenesis of HP.

Alveolitis, Extrinsic Allergic↗

PubMed2003

Enhancement of ultrasound-induced apoptosis and cell lysis by echo-contrast agents.

To determine the effects of echo-contrast agents (ECAs) on ultrasound (US)-induced apoptosis and cell lysis, human myelomonocytic lymphoma U937 cells in suspension were exposed to 1 MHz continuous waves US for 1 min at an intensity of 0.5, 1.0, 2.0 or 4.0 W/cm(2) with or without non-shell type ECA, Levovist (2 mg/ml), and shell type, Optison (1 microl/ml) or YM454 (1 microl/ml). Levovist minimally enhanced the US-induced apoptosis at 1.0 W/cm(2) while Optison and YM454 did at 2.0 and 4.0 W/cm(2), as detected by flow cytometry. Cell lysis was also augmented when Levovist was combined with US at 2.0 W/cm(2), and when Optison was combined with US at 2.0 and 4.0 W/cm(2). YM454 showed the highest rate of enhanced cell lysis at 1.0, 2.0 and 4.0 W/cm(2). Therefore, this study shows that Optison and YM454 are effective in augmenting the US-induced cell killing, but not Levovist. Another result indicates that cavitation plays a role in the augmented effects and that inertial cavitation appears necessary for Optison and YM454 to effect their actions. In addition, results show that the rate of apoptosis is lower in the presence of ECAs with higher free radical scavenging activity, suggesting a possible role for free radicals in apoptosis. These findings suggest that some ECAs have potential to be adjuncts in cases wherein augmented US-induced cell killing is needed, such as in cancer therapy with US.

Albumins↗

PubMed2003

The molecular mechanism of arsenic trioxide-induced apoptosis and oncosis in leukemia/lymphoma cell lines.

The mechanisms of As(2)O(3)-induced apoptosis are very complex. In the present study, we investigated the molecular mechanism of As(2)O(3) in vitro at low concentration (0.25-2.0 micro M) on three human leukemia/lymphoma cell lines: HL-60, RL and K562. As(2)O(3) inhibited the growth of these cell lines significantly. During As(2)O(3) treatment, two forms of cell death, apoptosis in HL-60 and RL and oncosis in K562, were found by morphological study. In HL-60 and RL, cell cycle analysis showed, at a distinct SubG1 region, that CD95 and CD95 ligand (CD95L) expression was upregulated, caspase 8 and caspase 3 were activated, and Bcl-2 protein expression was downregulated. On the other hand, in K562, the cell cycle was arrested at the G2+M phase, CD95/CD95L expression was upregulated, caspase 8 and caspase 3 were activated, but Bcl-2 expression was not changed as compared with untreated cells. These findings suggest that the CD95/CD95L pathway is involved in cell killing by As(2)O(3). Using anti-CD95 IgG monoclonal antibody (anti-CD95 MoAb) or specific caspase inhibitor ZVAD-fmk to block the CD95 pathway, the cell death induced by As(2)O(3) was partially blocked in each cell line. These results suggest that As(2)O(3) inhibits the growth of these leukemia/lymphoma cell lines by inducing apoptosis or oncosis that is partially mediated by the CD95/CD95L pathway.

Acute Disease↗

PubMed2003

[Intravenous myocardial contrast echocardiography; recent advances].

Until quite recently, contrast echocardiography for myocardial perfusion imaging has required the invasive direct injection of contrast agent into the coronary artery. Recent advances in ultrasonic technology and contrast agents have enabled myocardial contrast echocardiography with intra-venous injection of contrast agent in the clinical setting. This noninvasive technique has made the following clinical applications; left ventricular opacification, determination of the endocardium, enhancement of the Doppler flow signals, and detection of myocardial perfusion. Furthermore, in the near future, local drug delivery and pathology-specific targeted adherence of contrast agent may be added to the applications for the treatment. Intravenous myocardial contrast echocardiography is expected to have wide-ranging clinical potential.

Contrast Media↗

PubMed2002

Primary systemic amyloidosis presenting as angina pectoris due to intramyocardial coronary artery involvement: a case report.

We describe a 76-year-old Japanese woman with primary systemic amyloidosis who presented with angina pectoris associated with ST-segment and T-wave abnormalities resulting from intramyocardial coronary artery amyloidosis. The patient was admitted to our hospital because of dyspnea and pretibial edema 7 years after the diagnosis of variant angina. A diagnosis of primary systemic amyloidosis (AL amyloid protein) was made after examination of gastric and endomyocardial biopsy specimens. The patient died of progressive, uncontrolled heart failure 3 months later. An autopsy study demonstrated only mild-to-moderate atherosclerosis in the epicardial coronary arteries. However, histological examination of the heart revealed diffuse stenoses and obstructions in the intramural coronary arteries by amyloid deposits. This patient had small-vessel coronary disease with ST-segment changes and angina caused by cardiac amyloidosis. A correct diagnosis of ischemic heart disease due to primary amyloidosis is important for estimation of the prognosis and for appropriate management.

Aged↗

PubMed2002

Is the site of thrombus formation in the left atrial appendage associated with the risk of cerebral embolism?

Atrial fibrillation (AF) is a risk factor for cerebral embolism, with the left atrial appendage (LAA) being considered as the source of emboli. However, the relationship between the histologic properties of LAA thrombi and the occurrence of cerebral embolism is not known. Seventy-six hearts from patients who died within 1 month after cerebral embolism were studied at autopsy. Patients were grouped according to the presence of AF and the presence of valvular disease (VD). We determined whether the LAA thrombi adhered to the trabecular region or the remainder of the LAA. LAA thrombi were grouped into three stages: a fresh stage in which thrombi consisted of fibrin and platelets, an organizing stage in which angiogenesis was observed in the thrombi, and an organized stage in which endothelial cells covered the surface of the thrombi. The AF+/VD- group included 19 patients (25.0%), the AF+/VD+ group 8 (10.5%), the AF-/ VD- group 37 (48.7%), and the AF-/VD+ group included 12 patients (15.8%). LAA thrombi were observed in 15 patients (78.9%) in the AF+/VD- group, and all of the thrombi adhered to the trabecular region. Thrombi in the fresh and the organizing stages were observed in 10 patients (66.7%). Patients in the AF+/VD- group accounted for about 25% of the cases of cerebral embolism. All of these thrombi were attached to the trabecular region, and about 70% of them could represent an embolic source.

Adult↗

PubMed2002

Interleukin-6-producing thymic squamous cell carcinoma associated with Castleman's disease and nephrotic syndrome.

When a 63-year-old man was hospitalized with nephrotic syndrome due to focal segmental glomerulosclerosis, a mediastinal mass was discovered. A biopsy specimen obtained by mediastinoscopy showed findings compatible with the plasma cell type of Castleman's disease. Fever, anemia, and anti-nuclear antibody were present. Serum concentrations of gamma globulin, acute phase proteins, and, most strikingly, interleukin-6 (IL-6) were elevated. Methylprednisolone pulse therapy resulted in no clinical improvement. Pathologic examination of the resected thymic tumor showed a squamous cell carcinoma immunoreactive for IL-6. To our knowledge, this case represents the first reported IL-6-producing thymic squamous cell carcinoma associated with Castleman's disease and nephrotic syndrome.

Carcinoma, Squamous Cell↗

PubMed2002

[Report of a patient of primary Sjögren syndrome, IgA nephropathy and chronic idiopathic thrombocytopenic purpura].

We describe the case of a 61-year-old woman diagnosed with primary Sjögren's syndrome (SS) after an 8-year history of IgA nephropathy and a 3-year history of recurrent purpuric rashes. Her two daughters had previously been diagnosed with other autoimmune diseases. One daughter had Graves' disease and the other had Hashimoto's disease and systemic lupus erythematosus. The diagnosis of SS was made based on dryness of mucous membranes, Shirmer test, and parotid sialography. Thrombocytopenia, high platelet-aggregated IgG (PA-IgG) level, and normal megakaryocytes count in bone marrow suggested that her recurrent purpuric rashes were due to idiopathic thrombocytopenic purpura (ITP). Patients with SS may develop other autoimmune diseases. This case aids understanding of the immune pathogenesis and genetic background of SS.

Chronic Disease↗

PubMed1996

Thyroid Carcinoma in Japan and the West: Similarities and Differences.

Geographic or ethnic differences in the incidence of thyroid carcinoma, as well as in the histologic distribution of thyroid carcinoma between Japan and Western countries, have been described but are still unclear. The recent establishment of histologic criteria for the diagnosis of thyroid carcinoma by the WHO committee has facilitated the comparison of clinicopathological data of patients with thyroid carcinoma all over the world. The aim of the present review article is to clarify the epidemiological and clinicopathological differences of thyroid carcinoma between Japan and Western countries. We found recently no significant differences in the incidence, mortality, and histologic distribution of thyroid carcinoma between Japan and Western countries; this was contrary to our expectation. This is likely attributable to westernization of the Japanese diet, standardized medical levels, and international standardization of histologic criteria of thyroid carcinoma.

Journal Article↗

PubMedDate not supplied

Arsenic trioxide induces apoptosis in leukemia/lymphoma cell lines via the CD95/CD95L system.

Although arsenic trioxide (As2O3) has been shown to be an effective anticancer agent for acute promyelocytic leukemia (APL), its mechanisms of action as well as its effect on other leukemias than APL remain unclear. We studied in vitro effects of As2O3 at low concentrations (1.0-2.0 microM) on two human leukemia/lymphoma cell lines, HL-60, an acute myeloid leukemia cell line, and RL, a B-cell lymphoma cell line. As2O3 inhibited proliferation of HL-60 cells and RL cells to the similar degree to the reported inhibition by an APL cell line, NB4. As2O3-treated cell lines exhibited typical morphologic changes of apoptosis such as nuclear condensation and apoptotic bodies, and a cell cycle arrest at the subG1 phase. As2O3-treated cell lines also showed upregulation of CD95/CD95L expression and activation of caspases 8 and 3. Treatment of these cells with anti-CD95 antibodies capable of blocking the CD95 signaling pathway ameliorated As2O3-induced apoptosis. These data suggest that As2O3 can inhibit growth of leukemia/lymphoma cells by inducing the cell cycle arrest and apoptosis that is partially mediated by the CD95/CD95L system.

Antibodies, Monoclonal↗