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Biomedical subjects

M Ninomiya

Publications and source records attributed to M Ninomiya.

At least 37 records · Page 2Linked to original sources

[A case of recurrent gastric cancer successfully treated with TS-1].

A patient with recurrent gastric cancer which infiltrated the pelvic muscle after the treatment of paraaortic lymph node and ovarian metastases was successfully managed by a novel oral anticancer drug, TS-1. TS-1 was administered at a dose of 80 mg/day. One course consisted of two repetitions of consecutive administration of TS-1 for 14 days and withdrawal of TS-1 for 14 days. Adverse reactions were mild and the patient did not request hospitalization after two courses had been completed. Subjective symptoms such as difficulty in walking improved after one week and a partial response was obtained after 2 weeks of treatment. At the end of 4 courses we could remove an indwelling pyelocatheter for the ureter stricture. As of 14 months after the beginning of administration of TS-1, the patient is being treated as an outpatient and has attained a better QOL than before.

Aged↗

alpha-eudesmol, a P/Q-type Ca(2+) channel blocker, inhibits neurogenic vasodilation and extravasation following electrical stimulation of trigeminal ganglion.

In this study, we investigated the effect of alpha-eudesmol, which potently inhibits the presynaptic omega-agatoxin IVA-sensitive (P/Q-type) Ca(2+) channel, on neurogenic inflammation following electrical stimulation of rat trigeminal ganglion. Treatment with alpha-eudesmol (0.1-1 mg/kg. i.v.) dose-dependently attenuated neurogenic vasodilation in facial skin monitored by a laser Doppler flowmetry. In addition, alpha-eudesmol (1 mg/kg. i.v.) significantly decreased dural plasma extravasation in analysis using Evans blue as a plasma marker. On the other hand, alpha-eudesmol (1 mg/kg, i.v.) did not affect mean arterial blood pressure in rats. The calcitonin gene-related peptide (CGRP) and substance P (SP) released from activated sensory nerves have recently been suggested to be associated with the neurogenic inflammation. In this study, we also showed that alpha-eudesmol (0.45-45 microM) concentration-dependently inhibits the depolarization-evoked CGRP and SP release from sensory nerve terminals in spinal cord slices. These results indicate that the anti-neurogenic inflammation action of alpha-eudesmol, which does not affect the cardiovascular system, may be due to its presynaptic inhibition of the neuropeptide release from perivascular trigeminal terminals. We also suggest that the omega-agatoxin IVA-sensitive Ca(2+) channel blocker, alpha-eudesmol, may become useful for the treatment of the neurogenic inflammation in the trigemino-vascular system such as migraine.

Animals↗

Long-term right ventricular volume overload increases myocardial fluorodeoxyglucose uptake in the interventricular septum in patients with atrial septal defect.

BACKGROUND: Several studies have shown that long-term right ventricular (RV) overload in animal models alters myocardial energy substrate metabolism. However, whether long-term RV volume overload alters this metabolism in the human is unclear. METHODS AND RESULTS: We performed positron emission tomography with [(18)F]fluorodeoxyglucose (FDG) and single-photon emission tomography (SPECT) with [(201)Tl]TlCl (Tl) and [(123)I]15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in 11 patients with atrial septal defect (ASD) and 11 control subjects. In the FDG study, we calculated myocardial metabolic rate of glucose (MMR) in interventricular septum (IVS) and left ventricular (LV) free wall. MMR was significantly increased in IVS compared with LV free wall in the ASD patients (420+/-35 versus 333+/-32 mol x kg(-1) x min(-1); P<0.05) but not in the control group (347+/-27 versus 357+/-25 mol x kg(-1) x min(-1)). In both ASD and control groups, SPECT count was not significantly different between IVS and LV free wall in Tl (ASD, 160+/-11 versus 177+/-12; control, 141+/-12 versus 157+/-14 counts per 15 minutes) and BMIPP studies (ASD, 203+/-14 versus 212+/-18; control, 162+/-16 versus 176+/-16 counts per 15 minutes). MMR in the IVS/LV free wall ratio in the ASD group significantly correlated with indices related to RV volume overload. CONCLUSIONS: Given the assumption that long-term RV volume overload did not affect the lumped constant, the present study suggests that, unlike myocardial perfusion or fatty acid analogue uptake, myocardial glucose utilization in IVS relative to LV free wall is increased in relation to long-term RV volume overload in patients with ASD.

Adult↗

omega-agatoxin IVA-sensitive Ca(2+) channel blocker, alpha-eudesmol, protects against brain injury after focal ischemia in rats.

omega-Agatoxin IVA-sensitive Ca(2+) channels have been thought to be involved in physiological excitatory amino acid glutamate release and these channels may also contribute to the development of ischemic brain injury. Recently, we demonstrated that alpha-eudesmol from Juniperus virginiana Linn. (Cupressaceae) inhibits potently the presynaptic omega-agatoxin IVA-sensitive Ca(2+) channels. In the present study, we investigated the effects of alpha-eudesmol on brain edema formation and infarct size determined after 24 h of reperfusion following 1 h of middle cerebral artery occlusion in rats. We first found that alpha-eudesmol concentration-dependently inhibited glutamate release from rat brain synaptosomes and that its inhibitory effect was Ca(2+)-dependent. In the middle cerebral artery occlusion study, intracerebroventricular (i.c.v.) treatment with alpha-eudesmol significantly attenuated the post-ischemic increase in brain water content. alpha-Eudesmol also significantly reduced the size of the infarct area determined by triphenyltetrazolium chloride staining after 24 h of reperfusion. Using a microdialysis technique, we further demonstrated that alpha-eudesmol inhibits the elevation of the extracellular concentration of glutamate during ischemia. From these results, we suggest that alpha-eudesmol displays an ability to inhibit exocytotic glutamate release and to attenuate post-ischemic brain injury.

Animals↗

Cyclosporin A decreases the degradation of type I collagen in rat gingival overgrowth.

Cyclosporin A (CsA) is used as an immunosuppressive agent and its prominent side effect is the induction of fibrous gingival overgrowth. The purpose of this study was to investigate the effect of CsA on the type I collagen metabolism in the gingiva of rats fed a powdered diet either containing or lacking CsA. Immunohistochemical analysis revealed that type I collagen was more prevalent in the connective tissue of CsA-treated gingiva than in those of control rats on days 15, 30, and 55 after the start of feeding. Total RNAs were isolated from mandibular molar gingiva on days 0, 3, 8, 15, 30, and 55. Quantitative analysis of mRNA by reverse transcriptase-polymerase chain reaction revealed that the CsA-treated groups showed a gradual decrease in expression of type I collagen and collagenase mRNAs, 0.4% and 18.0% on day 55 compared with those on day 0, respectively. In the control groups, type I collagen and collagenase mRNAs also decreased to 19.7% and 63.0%, respectively, however, both mRNA expressions were significantly lower in the CsA-treated group than in the controls. An electron microscopic analysis of fibroblasts was performed to count the number of cells with collagen fibrils in the cytoplasm, a marker of phagocytosis of collagen by fibroblasts. The collagen fibrils were detected in 4.7% +/- 2.7% and 24.3% +/- 13.7% of fibroblasts in the overgrown gingiva treated with CsA rat for 8 days and 30 days, but in 57.0% +/- 5.3% and 81.3% +/- 9.2% of fibroblasts in the each control group gingiva, respectively. Furthermore, in vitro analysis was performed to measure the phagocytosis of cultured fibroblasts by flow cytometry using collagen-coated latex beads. Fibroblasts isolated from CsA-treated gingiva on day 8 and day 30 contained 5.7% +/- 0.6% and 9.9% +/- 1.5% phagocytic cells, whereas control fibroblasts contained 50.3% +/- 5.5% and 33.3% +/- 4.9% phagocytic cells, respectively. The inhibition rate of phagocytic activity was similar between in vivo and in vitro assays. These findings suggest that the decrease of the collagen degradation due to the lower phagocytosis and the lower collagenase mRNA expression are closely associated with the increase of type I collagen accumulation in CsA-treated rat gingiva.

Animals↗

Translocation of aortic valve for calcific aortic stenosis.

A 56-year-old man underwent surgery for treatment of severe calcific aortic stenosis. Because it was found after excision of the aortic valve that calcification of the annulus was too extensive for the placement of sutures, translocation of the aortic valve was performed. The results were satisfactory and indicate that translocation is a useful alternative in cases of severe calcification of the aortic valve which cannot be treated by ordinary valve replacement.

Aortic Valve↗

Cardiac function evaluated by transesophageal echocardiography during cardiopulmonary bypass.

OBJECTIVE: To evaluate cardiac function at cardiopulmonary bypass weaning, we applied a new technique clinically to determine the approximated Emax without using a conductance catheter. METHODS: Subjects were 5 patients. The left ventricular end-systolic pressure was obtained by overlaying the radial arterial pressure curve on the left ventricular pressure curve. Left ventricular end-systolic volume was assessed by a transesophageal echographic apparatus. At cardiopulmonary bypass weaning, volume loading was applied to increase left atrial pressure by a few mmHg while fixing the pump flow rate at half flow. Changes in left ventricular end-systolic volume and approximated left ventricular end-systolic pressure for total heart beat were plotted during this period, and the gradient of the regression line was taken as approximated Emax. RESULTS: Approximated Emax ranged from 1.29 to 3.28 (mean 2.13 +/- 0.72), and its correlation coefficient was 0.80 +/- 0.06. CONCLUSION: Our new technique is useful in evaluating cardiac function during cardiopulmonary bypass.

Adult↗

Ultrasonic aortic valve decalcification.

We report a case of calcific aortic stenosis in a 79-year-old man who had undergone aortocoronary bypass. Since ordinary valve replacement was problematic because of severe annular calcification, a small annular diameter, and three patent vein grafts, we performed ultrasonic aortic valve decalcification. As a result, the pressure gradient across the aortic valve decreased from 100 mmHg to 25 mmHg, and the patient is doing well to date at two years after the operation. Although long-term results of ultrasonic aortic valve decalcification are still undetermined, it appears worth considering in cases in which ordinary valve replacement could be extremely difficult.

Aged↗

Large pulmonary arteriovenous fistula.

A 55-year-old woman with Rendu-Osler-Weber disease underwent surgical resection of a pulmonary arteriovenous fistula deriving from right middle lobe vessels. The fistula was 10 x 6 x 5 cm, to our knowledge, the largest ever reported. Although the major part of the fistula was well exposed through median sternotomy, extensive bleeding during dissection of feeding and drainage vessels precluded safe dissection. Total cardiopulmonary bypass was therefore used to divert the pulmonary blood flow. Anatomy was clearly delineated and connecting vessels were safely suture-closed from within the fistula without sacrificing the right middle lobe vein, which might have been damaged without cardiopulmonary bypass. The postoperative course was uneventful, and no complications associated with cardiopulmonary bypass occurred.

Arteriovenous Fistula↗

Descending aortic aneurysm with Takayasu's disease.

A 69-year-old woman with Takayasu's disease was referred to our hospital for surgical treatment of a descending aortic aneurysm. Preoperative angiography and computed tomography revealed abdominal aortic stenosis and severe calcification in the descending aorta. The abdominal aorta was first replaced, since the aortic stenosis would have disturbed blood flow to the abdominal organs during extracorporeal circulation, which would be needed for subsequent thoracic surgery. The descending aortic aneurysm was then resected under femoro-femoral bypass. Since the descending aorta was severely calcified, two occlusion balloon catheters were used to clear the aorta. After aortic walls just proximal and distal to the aneurysm were decalcified, a short prosthetic tube graft was anastomosed. Only 2 pairs of intercostal arteries were sacrificed and paraplegia was prevented. Vascular lesions must thus be accurately evaluated and suitable procedures selected in surgically treating Takayasu's disease.

Aged↗

Surgical management of ascending aortic graft infection. No-sedation-technique for open mediastinal irrigation.

Two patients with ascending aortic graft infection were successfully treated. The first patient underwent ascending aortic replacement using a Dacron graft for aortic dissection, and developed graft infection. After 25 days' open mediastinal irrigation, allograft replacement and rectus muscle flap transfer were performed. The second patient underwent translocation of the aortic valve with a composite graft for calcific aortic stenosis, and developed graft infection. After 29 days' open irrigation, omental and rectus muscle flap transfer were performed. We were able to perform long-term open mediastinal irrigation using our original no-sedation-technique without any severe complication such as bleeding or secondary infection. We believe this technique is helpful in the management of severe ascending aortic graft infection.

Aortic Dissection↗

Hypertrophic obstructive cardiomyopathy associated with mitral regurgitation due to infective endocarditis.

A 25-year-old woman treated for hypertrophic obstructive cardiomyopathy and suffering from mitral regurgitation due to infective endocarditis was referred to our department for surgery. Preoperative examinations revealed asymmetric septal hypertrophy, a large left ventricular outflow gradient (100 mmHg), and perforation of the anterior mitral leaflet resulting in severe mitral regurgitation. The entire mitral complex was resected and septal myectomy conducted to dilate the left ventricle. A bioprosthetic valve was then implanted. Although postoperative heart failure was severe, cardiac function has gradually recovered. The left ventricular outflow gradient has decreased to 8 mmHg, the diastolic left ventricular diameter has increased from 26 to 30 mm, and her New York Heart Association classification has improved from IV to I.

Adult↗

[Living donor liver transplantation in Kyushu University].

We performed living donor liver transplantation (LDLT) for 40 patients at Kyushu University Hospital, Fukuoka Japan during the period from October 1996 to April 2000. The patients consisted of 32 adults and 8 children with a mean age of 35.8 years (range: 1 year and 10 months to 65 years old). The underlying liver diseases of the 40 patients included the fulminant hepatic failure (n = 14), biliary atresia (n = 7), liver cirrhosis (HCV) (n = 6), primary biliary cirrhosis (n = 5), primary sclerosing cholangitis (n = 2), familiar amyloidotic polyneuropathy (n = 2), Alagille syndrome (n = 1), glycogen storage disease (n = 1), huge hepatic hemangiomas (n = 1), and Wilson's disease (n = 1). All liver grafts were obtained from each patient's family members except for one domino transplant donor's case, comprised of 13 parents, 13 sons and daughters, 11 brothers and sisters, and 3 wives. The donors are presently all doing well. The patient survival rate is presently 92.5%.

Adolescent↗

The nonpeptide alpha-eudexp6l from Juniperus virginiana Linn. (Cupressaceae) inhibits omega-agatoxin IVA-sensitive Ca2+ currents and synaptosomal 45Ca2+ uptake.

Recently, the omega-agatoxin IVA (omega-Aga-IVA)-sensitive Ca2+ channel has been demonstrated to play an important role in the physiological neurotransmitter release in mammalian nerve terminals. In this study, we demonstrate that alpha-eudesmol from Juniperus virginiana Linn. (Cupressaceae) inhibits omega-Aga-IVA-sensitive Ca2+ channels in rat brain synaptosomes and cerebellar Purkinje cells. Thirty millimolar KCl-induced 45Ca2+ uptake into the synaptosomes was inhibited by omega-Aga-IVA but insensitive to omega-conotoxin GVIA (omega-CTX-GVIA, N-type Ca2+ channel blocker) and nicardipine (L-type Ca2+ channel blocker). We found that alpha-eudesmol concentration-dependently inhibited the above synaptosomal 45Ca2+ uptake with an IC50 value of 2.6 microM. Co-treatment with alpha-eudesmol and omega-Aga-IVA did not cause any additive inhibitory effect against the synaptosomal 45Ca2+ uptake. Using the whole-cell patch clamp electrophysiological technique, we further demonstrated that alpha-eudesmol concentration-dependently inhibited omega-Aga-IVA-sensitive Ca2+ channel currents recorded from Purkinje cells with an IC50 value of 3.6 microM. The current-voltage relationship of the omega-Aga-IVA-sensitive Ca2+ channel currents was not changed by alpha-eudesmol. On the other hand, alpha-eudesmol also displayed an inhibitory effect on N-type Ca2+ channel currents recorded from differentiated NG108-15 cells with an IC50 value of 6.6 microM. However, alpha-eudesmol had little inhibitory effect on L-type Ca2+ channel currents. Thus, the present data indicated that alpha-eudesmol is a potent nonpeptidergic compound which blocks the presynaptic omega-Aga-IVA-sensitive Ca2+ channel with relative selectivity.

Animals↗

Type I acute aortic dissection accompanied by ischemic enterocolitis due to blood flow insufficiency in the superior mesenteric artery.

We report a case of acute type I aortic dissection with ischemic enterocolitis due to blood flow insufficiency in the superior mesenteric artery. The patient was a 52-year-old man who visited the hospital with major complaints of sudden low back pain and melena. Mesenteric ischemia was suspected, and angiography revealed type I aortic dissection with accompanying blood flow insufficiency in the superior mesenteric artery. Because catheterization during angiography improved the blood flow disorder and prevented intestinal necrosis, it was possible to replace the ascending aorta with a prosthetic graft. Arterial pulsation in the mesentery was recovered by the operation and the patient's life was saved without bowel resection. This case demonstrates that prompt surgical or percutaneous relief of ischemia in major organs is important to save lives in the cases of acute aortic dissection with ischemic complications.

Acute Disease↗

Screening of lipase inhibitors from marine algae.

The possible presence of an inhibitor of pancreatic lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) was screened in 54 marine algae. An active inhibitor, caulerpenyne, was purified from an extract of Caulerpa taxifolia, using ethyl acetate extraction, followed by successive chromatographies on ODS and silica gel columns. The purified inhibitor was identified by thin-layer chromatography, infrared and nuclear magnetic resonance spectroscopy. Caulerpenyne competitively inhibited lipase activities using emulsified triolein and dispersed 4-methylumbelliferyl oleate (4-MU oleate) as substrates. The concentrations producing 50% inhibition against triolein and 4-MU oleate hydrolysis were 2 mM and 13 microM, respectively. In vivo, oral administration of corn oil with or without caulerpenyne to rats demonstrated a reduced and delayed peak plasma triacylglycerol concentration with caulerpenyne.

Administration, Oral↗

Tea catechin supplementation increases antioxidant capacity and prevents phospholipid hydroperoxidation in plasma of humans.

The effect of green tea catechin supplementation on antioxidant capacity of human plasma was investigated. Eighteen healthy male volunteers who orally ingested green tea extract (254 mg of total catechins/subject) showed 267 pmol of epigallocatechin-3-gallate (EGCg) per milliliter of plasma at 60 min after administration. The plasma phosphatidylcholine hydroperoxide (PCOOH) levels attenuated from 73.7 pmol/mL in the control to 44.6 pmol/mL in catechin-treated subjects, being correlated inversely with the increase in plasma EGCg level. The results suggested that drinking green tea contributes to prevent cardiovascular disease by increasing plasma antioxidant capacity in humans.

Adult↗

Endothelium-independent vascular relaxation mediating ETB receptor in rabbit mesenteric arteries.

Vascular response mediating endothelin (ET)B receptor was studied using isolated rabbit mesenteric arteries. ET-1 (0.1-30 nM) caused a concentration-dependent contraction, whereas ET-3 >100 nM caused only weak contraction. Up to 1 microM of sarafotoxin S6c showed no contraction. In arteries precontracted with phenylephrine, ET-3 (0. 03-1 nM) caused a concentration-dependent relaxation, which was not affected by endothelium denudation. The ET-3-induced relaxation was antagonized by BQ-788 and PD-142893 but not by BQ-123 in the endothelium-denuded arteries. Treatment with indomethacin but not with NG-nitro-L-arginine methyl ester completely inhibited the relaxation. ET-3 stimulated the release of 6-keto-PGF1alpha and PGE2 from the endothelium-denuded arteries. ET-3 also significantly increased cAMP content but not cGMP content in the arteries. Radioligand-binding studies using serial sections of the artery revealed the expression of not only ETA but also ETB receptors in the smooth muscle layer of the arteries. These results suggest that ET-3 activates ETB receptor in smooth muscle cells of rabbit mesenteric artery, producing vasodilator prostaglandins from arachidonic acid probably via a catalysis of cyclooxygenase, which accumulates cAMP in subendothelial tissues and produces relaxations.

Animals↗