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Biomedical subjects

N Sekiguchi

Publications and source records attributed to N Sekiguchi.

At least 19 recordsLinked to original sources
PubMed2005

Long-term follow-up results of no initial therapy for ocular adnexal MALT lymphoma.

BACKGROUND: The majority of lymphomas in the ocular adnexa are low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma). Although radiotherapy is the most frequently applied management, cataract and dry eye are problematic complications. PATIENTS AND METHODS: Between 1973 and 2003, the clinical features of 36 patients with ocular adnexal MALT lymphoma with no symptoms who were managed with no initial therapy after biopsy or surgical resection were retrospectively analyzed. RESULTS: The median patient age was 63 years (range 22-84) and all patients had stage I disease, consisting of 31 unilateral cases and five bilateral cases. With a median follow-up of 7.1 years, 25 (69%) did not require treatment. The median time until the initiation of treatment in the remaining 11 patients (31%) was 4.8 years. Six patients (17%) died, and among them only two (6%) died due to progressive lymphoma. Seventeen patients (47%) progressed, but histologic transformation was recognized in only one (3%). The estimated overall survival rates of the 36 patients after 5, 10 and 15 years were 94%, 94% and 71%, respectively. CONCLUSIONS: In selected patients with ocular adnexal MALT lymphoma, no initial therapy might be an acceptable approach, because 70% of patients remained untreated at a median of 8.6 years, and their survival was comparable to that of reports on immediate therapy.

Adult↗
PubMed2005

CD2+ acute promyelocytic leukemia is associated with leukocytosis, variant morphology and poorer prognosis.

The T cell-lineage marker CD2 is sometimes expressed in acute promyelocytic leukemia (APL), and CD2 expression is reported to correlate with some clinical characteristics. However, the significance of CD2 expression in APL has not been fully elucidated. We evaluated CD2 expression in APL treated by the same treatment strategy in a single institute, and whether it had any special characteristics. Among 29 APL, 6 were positive for CD2. Patients with CD2+ APL tended to have a higher leukocyte count than CD2- APL (34.5 +/- 13.1/l vs. 6.8 +/- 2.1/l), morphological characteristics as variant-APL (50 vs. 0%). They also showed poor clinical prognosis. The CR rate of CD2- APL was 87.0% while that of CD2+ APL was 50 %. The mortality was 13.0 and 66.7%, respectively, and the survival rate was significantly lower in CD2+ APL. CD2 expression was proven to be a risk factor associated with death in addition to the morphological characteristics of variant-APL and leukocytosis. These results indicated that CD2 expression might have a significant impact on the prognosis of APL. Whether CD2+ APL should be characterized as a special clinical entity should be discussed in a larger patient population.

Adult↗
PubMed2003

A possible target of antioxidative therapy for diabetic vascular complications-vascular NAD(P)H oxidase.

A growing body of evidence has shown that oxidative stress may be involved in the development of vascular complications associated with diabetes. However, the molecular mechanism for increased reactive oxygen species (ROS) production in diabetes remains uncertain. Among various possible mechanisms, attention have increasingly been paid to NAD(P)H oxidase as the most important source of ROS production in vascular cells. High glucose level stimulates ROS production through protein kinase C (PKC)-dependent activation of vascular NAD(P)H oxidase. Furthermore, the expression of NAD(P)H oxidase components is increased in micro- and macrovascular tissues of diabetic animals in association with various functional disorders and histochemical abnormalities. These results suggest that vascular NAD(P)H oxidase-driven ROS production may contribute to the onset or development of diabetic micro- or macrovascular complications. In this point of view, the possible new strategy of antioxidative therapy for diabetic vascular complications is discussed in this review.

Animals↗
PubMed2000

Reduced voltage sensitivity of activation of P/Q-type Ca2+ channels is associated with the ataxic mouse mutation rolling Nagoya (tg(rol)).

Recent genetic analyses have revealed an important association of the gene encoding the P/Q-type voltage-dependent Ca(2+) channel alpha(1A) subunit with hereditary neurological disorders. We have identified the ataxic mouse mutation, rolling Nagoya (tg(rol)), in the alpha(1A) gene that leads to a charge-neutralizing arginine-to-glycine substitution at position 1262 in the voltage sensor-forming segment S4 in repeat III. Ca(2+) channel currents in acutely dissociated Purkinje cells, where P-type is the dominant type, showed a marked decrease in slope and a depolarizing shift by 8 mV of the conductance-voltage curve and reduction in current density in tg(rol) mouse cerebella, compared with those in wild-type. Compatible functional change was induced by the tg(rol) mutation in the recombinant alpha(1A) channel, indicating that a defect in voltage sensor of P/Q-type Ca(2+) channels is the direct consequence of the tg(rol) mutation. Furthermore, somatic whole-cell recording of mutant Purkinje cells displayed only abortive Na(+) burst activity and hardly exhibited Ca(2+) spike activity in cerebellar slices. Thus, in tg(rol) mice, reduced voltage sensitivity, which may derive from a gating charge defect, and diminished activity of the P-type alpha(1A) Ca(2+) channel significantly impair integrative properties of Purkinje neurons, presumably resulting in locomotor deficits.

Action Potentials↗
PubMed2000

[Significance of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) activity in breast cancer tissue].

TS, DPD, uridine phosphorylase and thymidine phosphorylase are enzymes involved in the metabolism of the anticancer drug pyrimidine fluoride. In this study, levels of these enzymes were measured in 47 women with primary breast cancer. These enzyme levels were then compared to levels determined from breast cancer patients who received either preoperative chemotherapy or nothing, in order to determine whether they might predict clinical outcome. The TS inhibition rate was significantly higher (p < 0.05) in patients receiving preoperative chemotherapy (20.4 +/- 13.3%) than in the untreated group (11.4 +/- 9.8%). No other significant differences in activity were noted between the treated and untreated groups for any of the other enzymes studied. The activity of each enzyme at the tumor site and the tumor/normal (T/N) ratio were also compared between patients with and without recurrence. The TS inhibition rate at the tumor site was lower in recurring cases than in non-recurring cases, and the T/N ratio tended to be higher for DPD in patients with recurrences. These findings indicate that the TS inhibition rate and DPD activity may be useful predictors for early recurrence of breast cancer following surgery.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Single tottering mutations responsible for the neuropathic phenotype of the P-type calcium channel.

Recent genetic and molecular biological analyses have revealed many forms of inherited channelopathies. Homozygous ataxic mice, tottering (tg) and leaner (tgla) mice, have mutations in the P/Q-type Ca2+ channel alpha1A subunit gene. Although their clinical phenotypes, histological changes, and locations of gene mutations are known, it remains unclear what phenotypes the mutant Ca2+ channels manifest, or whether the altered channel properties are the primary consequence of the mutations. To address these questions, we have characterized the electrophysiological properties of Ca2+ channels in cerebellar Purkinje cells, where the P-type is the dominant Ca2+ channel, dissociated from the normal, tg, and tgla mice, and compared them with the properties of the wild-type and mutant alpha1A channels recombinantly expressed with the alpha2 and beta subunits in baby hamster kidney cells. The most striking feature of Ca2+ channel currents of mutant Purkinje cells was a marked reduction in current density, being reduced to approximately 60 and approximately 40% of control in tg and tgla mice, respectively, without changes of cell size. The Ca2+ channel currents in the tg Purkinje cells showed a relative increase in non-inactivating component in voltage-dependent inactivation. Besides the same change, those of the tgla mice showed a more distinct change in voltage dependence of activation and inactivation, being shifted in the depolarizing direction by approximately 10 mV, with a broader voltage dependence of inactivation. In the recombinant expression system, the tg channel with a missense mutation (P601L) and one form of the two possible tgla aberrant splicing products, tgla (short) channel, showed a significant reduction in current density, while the other form of the tgla channels, tgla (long), had a current density comparable to the normal control. On the other hand, the shift in voltage dependence of activation and inactivation was observed only for the tgla (long) channel. Comparison of properties of the native and recombinant mutant channels suggests that single tottering mutations are directly responsible for the neuropathic phenotypes of reduction in current density and deviations in gating behavior, which lead to neuronal death and cerebellar atrophy.

Animals↗
PubMed1998

Two regions of the ryanodine receptor involved in coupling with L-type Ca2+ channels.

Ryanodine receptors (RyRs) are present in the endoplasmic reticulum of virtually every cell type and serve critical roles, including excitation-contraction (EC) coupling in muscle cells. In skeletal muscle the primary control of RyR-1 (the predominant skeletal RyR isoform) occurs via an interaction with plasmalemmal dihydropyridine receptors (DHPRs), which function as both voltage sensors for EC coupling and as L-type Ca2+ channels (Rios, E., and Brum, G. (1987) Nature 325, 717-720). In addition to "receiving" the EC coupling signal from the DHPR, RyR-1 also "transmits" a retrograde signal that enhances the Ca2+ channel activity of the DHPR (Nakai, J., Dirksen, R. T., Nguyen, H. T., Pessah, I. N., Beam, K. G., and Allen, P. D. (1996) Nature 380, 72-76). A similar kind of retrograde signaling (from RyRs to L-type Ca2+ channels) has also been reported in neurons (Chavis, P., Fagni, L., Lansman, J. B., and Bockaert, J. (1996) Nature 382, 719-722). To investigate the molecular mechanism of reciprocal signaling, we constructed cDNAs encoding chimeras of RyR-1 and RyR-2 (the predominant cardiac RyR isoform) and expressed them in dyspedic myotubes, which lack an endogenous RyR-1. We found that a chimera that contained residues 1,635-2,636 of RyR-1 both mediated skeletal-type EC coupling and enhanced Ca2+ channel function, whereas a chimera containing adjacent RyR-1 residues (2, 659-3,720) was only able to enhance Ca2+ channel function. These results demonstrate that two distinct regions are involved in the reciprocal interactions of RyR-1 with the skeletal DHPR.

Animals↗
PubMed1998

Effect of high glucose concentrations on prostacyclin-stimulating factor mRNA expression in cultured aortic smooth muscle cells.

Prostacyclin (PGI2) is a potent vasoactive prostanoid regulating vascular tone. We recently purified and cloned a PGI2-stimulating factor (PSF), which stimulates PGI2 production by vascular endothelial cells (ECs). Previous study demonstrated that PSF is predominantly located in vascular smooth muscle cells (SMCs) and present in serum. PSF may act on vascular ECs to regulate PGI2 synthesis for maintaining vessel wall homeostasis. Decreased PSF production in the vessel wall may result in an imbalance of prostanoid synthesis, leading to the development of vascular lesions such as diabetic angiopathy. In the present study, to investigate the regulatory mechanisms of PSF gene expression, we examined the effect of high glucose concentrations on PSF mRNA expression in cultured bovine aortic SMCs. Expression of PSF mRNA was significantly decreased to 66+/-6% of control value (p < 0.01), when the glucose level was raised from 5.5 to 27.8 mmol/l. We also examined the effect of osmolarity on PSF mRNA expression by addition of an appropriate dose of mannitol to the culture medium. We confirmed that high glucose concentration itself reduced the expression of PSF mRNA and glucose had much more effect than the osmolarity control. The expression of PSF mRNA was significantly decreased to 72+/-5% of control value (p < 0.05) by a protein kinase C (PKC) activator, phorbol-12-myristate-13-acetate (PMA). The decreased expression of PSF mRNA in the presence of high glucose or PMA was restored by co-incubation with a PKC-specific inhibitor (GF109203X). These results suggest that PSF gene expression in vascular SMCs may be decreased via a specific effect of high glucose concentrations. High glucose-induced activation of PKC is suggested to participate partly in the regulation of PSF gene expression.

Animals↗
PubMed1998

Increased mRNA expression of a novel prostacyclin-stimulating factor in human colon cancer.

We recently cloned a prostacyclin (PGl2)-stimulating factor (PSF), which stimulates PGl2 production by cultured vascular endothelial cells. Immunohistochemistry and Northern blot analysis demonstrated that PSF was highly expressed in colon cancer sites compared with normal colon mucosa obtained from the same patient, as well as in cultured adenocarcinoma cell lines compared with cultured normal colon mucosal cell lines. Increased levels of the PSF protein were detected in the culture media of these adenocarcinoma cells compared with levels in the culture media of normal mucosal cells. These results suggest that PSF is closely associated with carcinogenesis of colon mucosa.

Adenocarcinoma↗
PubMed1998

[Anesthetic management of abdominal gunshot wound--a report of three cases].

This is a case report of anesthetic management of abdominal gunshot wound. Two patients had upper abdominal wound involving the liver and the inferior vena cava. They died of uncontrolled bleeding. Third patient had lower abdominal injury involving the ascending colon and small intestine. The patient survived the injury and showed good recovery. In a case of the abdominal gunshot injury, prompt diagnosis and laparotomy are mandatory. Multiple intravenous routes are necessary in the upper part of the body for massive infusion and transfusion. Unusual hemostasis methods such as atrio-caval shunt or abdominal clamping of the aorta must be considered in case of injury in the inferior vena cava.

Abdominal Injuries↗
PubMed1997

Anti-atherogenicity in women does not prevent restenosis after balloon angioplasty.

To test the hypothesis that anti-atherogenicity in women exerts beneficial effects to prevent restenosis formation after coronary angioplasty, we studied 493 men (988 lesions) and 81 women (159 lesions), aged 40-60 years, who had undergone successful balloon angioplasty and had follow-up angiography, 4.9 +/- 4.1 months later. We compared the extent of restenosis between men and women, and between pre- and post-menopausal women, which was assessed by a categorical definition of restenosis (more than 50% diameter stenosis at follow-up) and by percent diameter measured immediately after angioplasty and at follow-up. Hypertension was more frequent in women and a significantly lower percentage of women smoked. In women, the levels of total cholesterol and low-density lipoprotein cholesterol were higher. The location of dilated lesions, frequency of angioplasty for lesions with chronic total occlusion, and frequency of emergency angioplasty in patients with unstable angina or acute myocardial infarction were similar in men and women. Restenosis formation, estimated by the categorical definition or percent diameter, did not differ between men and women, or between pre- and post-menopausal women. Menopausal status or sex was not an independent predictor of restenosis by multivariate analysis. Thus, the benefit of anti-atherogenicity in women does not play an important role in preventing restenosis after coronary angioplasty.

Adult↗
PubMed1997

Difference in serum-induced prostacyclin production by cultured aortic and capillary endothelial cells.

Prostacyclin (PGl2) generated by vascular endothelial cells play an important role in the maintenance of vessel wall homeostasis. Human plasma-derived serum (PDS) stimulated PGl2 synthesis by both cultured bovine aortic endothelial cells (BAEC) and adrenal capillary endothelial cells (BCEC), but the PGl2 response of the latter cells was far smaller. When BAEC were cultured with a high concentration of glucose (400 mg/dl), the PGl2 synthesis induced by 20% PDS was significantly lower than in the culture with a physiological concentration of glucose (100 mg/dl) (258 +/- 45 pg/10(4) cells/h vs. 402 +/- 52 pg/10(4) cells/h, n = 4, P < 0.05). On the other hand, there was no significant difference in the PDS-induced PGl2 synthesis between BCEC cultured with high and physiological concentrations of glucose. Additionally, 10% PDS obtained from patients with non-insulin dependent diabetes mellitus (n = 6) stimulated significantly less PGl2 synthesis than that from healthy subjects (n = 4) in the case of both BAEC (133 +/- 27 pg/10(4) cells/h vs. 402 +/- 38 pg/10(4) cells/h, P < 0.05) and BCEC (72 +/- 15 pg/10(4) cells/h vs. 118 +/- 12 pg/10(4) cells/h, P < 0.05), with the difference in PGl2 synthesis being smaller for BCEC. These findings indicate that the PDS-induced PGl2 synthesis differs between cultured vascular endothelial cells from large and small vessels with the decrease in PGl2 by diabetic PDS and high glucose being more marked for BAEC than BCEC.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Human diploid fibroblast cell culture medium contains a factor that increases cytosolic Ca2+ and stimulates prostaglandin synthesis by cultured bovine aortic endothelial cells.

Previously, we demonstrated that conditioned medium (CM) from cultures of human diploid fibroblast cells contains a factor that stimulates the production of prostacyclin (PGI2) by cultured bovine aortic endothelial cells (BAEC). To study the mechanism by which CM stimulates PGI2 production, we measured the effect of removal of extracellular calcium (Ca2+) on the concentration of cytosolic Ca2+ and on the production of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable metabolite of PGI2. The CM-induced production of 6-keto-PGF1 alpha was dependent on extracellular Ca2+ and did not require nascent protein synthesis. Application of CM to BAEC induced a transient increase in cytosolic Ca2+ concentration that was dependent on extracellular Ca2+. Bradykinin induced the production of 6-keto-PGF1 alpha by BAEC. However, bradykinin induced an increase in cytosolic Ca2+ concentration in the presence or absence of extracellular Ca2+. Voltage dependent Ca2+ channel blocker (verapamil, diltiazem) did not inhibit either the CM-induced increase in cytosolic Ca2+ or the production of 6-keto-PGF1 alpha by BAEC. These data suggest that CM increases the cytosolic Ca2+ concentration and stimulates PGI2 production by BAEC. The increase in cytosolic Ca2+ concentration occurred via the influx of extracellular Ca2+ independent of L-type Ca2+ channels blocked by verapamil or diltiazem.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

A case of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes associated with diabetes mellitus and hypothalamo-pituitary dysfunction.

A 45-year-old woman with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) had muscular atrophy, severe cerebral and cerebellar atrophy, and cardiac hypertrophy. She also had diabetes mellitus treated with insulin, and sensorineural hearing loss. Ragged-red fibers were observed on muscle biopsy and an adenine to guanine transition mutation at position 3243 of her mitochondrial DNA was confirmed. Further investigations revealed that she also had hypothalamo-pituitary dysfunction. It appears that diabetes mellitus, hypothalamo-pituitary dysfunction, and the other abnormalities are all associated with mitochondrial dysfunction in this patient.

Atrophy↗
PubMed1997

Immunohistochemical study of prostacyclin-stimulating factor (PSF) in the diabetic and atherosclerotic human coronary artery.

Prostacyclin (PGI2) synthesis by vascular endothelial cells (ECs) decreases in diabetic subjects, possibly leading to the development of diabetic angiopathy, such as that seen in atherosclerosis. We recently found a novel bioactive peptide, prostacyclin-stimulating factor (PSF), which stimulates PGI2 synthesis by cultured aortic ECs. Our previous studies demonstrated that PSF is dominantly expressed by arterial smooth muscle cells (SMCs). In the present study, we found PSF to exist in the SMCs of human coronary arteries by means of immunohistochemical methods. Human coronary arteries obtained from autopsies were divided into four subgroups, with or without NIDDM and/or myocardial infarction. Immunostaining for PSF was performed by the avidin-biotin peroxidase complex method using a purified anti-PSF antibody, and the immunostaining for PSF was assessed semiquantitatively. PSF staining was markedly reduced in coronary arterial SMCs from patients with NIDDM and/or myocardial infarction. In addition, the effect of a high glucose culture on PSF mRNA expression and PSF production in bovine aortic SMCs was examined by immunocytochemical staining and both Western and Northern blot analyses. The immunostaining and immunoblot band for PSF also significantly decreased when bovine aortic SMCs were cultured with high concentrations of glucose. Furthermore, as compared with the SMCs cultured with a physiological glucose concentration, the density ratio of PSF mRNA to 28S rRNA expression significantly decreased when the SMCs were cultured with high concentrations of glucose. These results strongly suggest that the decreased PSF production may thus results in a decreased production of PGI2 in the coronary artery, thus leading to the development of both diabetic macroangiopathy and atherosclerosis.

Adult↗