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Biomedical subjects

K Owada

Publications and source records attributed to K Owada.

At least 19 recordsLinked to original sources
PubMed2003

First results from KamLAND: evidence for reactor antineutrino disappearance.

KamLAND has measured the flux of nu;(e)'s from distant nuclear reactors. We find fewer nu;(e) events than expected from standard assumptions about nu;(e) propagation at the 99.95% C.L. In a 162 ton.yr exposure the ratio of the observed inverse beta-decay events to the expected number without nu;(e) disappearance is 0.611+/-0.085(stat)+/-0.041(syst) for nu;(e) energies >3.4 MeV. In the context of two-flavor neutrino oscillations with CPT invariance, all solutions to the solar neutrino problem except for the "large mixing angle" region are excluded.

Journal Article↗
PubMed2001

Cytoplasmic and nuclear polyglutamine aggregates in SCA6 Purkinje cells.

Aggregations of the alpha1A-calcium channel protein have been previously demonstrated in spinocerebellar ataxia type 6 (SCA6). Here the authors show that small aggregates, labeled by a monoclonal antibody 1C2 that preferentially detects expanded polyglutamine larger than that in SCA6 mutation, are present mainly in the cytoplasm but also in the nucleus of Purkinje cells. Although the length of expansion is small in SCA6, the current finding might indicate that SCA6 conforms to the pathogenic mechanism(s) in other polyglutamine diseases.

Brain↗
PubMed2001

Acute subdural hematoma in patients who underwent aneurysm clipping--four case reports.

Four patients presented with intracranial hemorrhage mainly consisting of acute subdural hematoma (ASDH), who had all undergone aneurysm clipping 2-20 years earlier. Whether the clips had slipped or new trauma had caused the bleeding was difficult to determine, since the initial computed tomography showed that the subarachnoid hemorrhage or the intracerebral hematoma developed near the clips. Angiography in three patients showed that the clips had not slipped off. Three of four ASDHs appeared in the same side as the craniotomy used for the previous aneurysm surgery. Anti-platelet agents and ventriculoperitoneal shunting had been previously used in two patients with no causal signs of trauma. The outcomes were poor in three patients and one patient died. Weakening of the extra- or intracranial structure after aneurysm surgery might have been involved together with the postoperative anti-platelet agent and shunt treatment in the etiology of the present ASDH.

Aged↗
PubMed2000

Long-term follow-up study of unruptured vertebral artery dissection: clinical outcomes and serial angiographic findings.

OBJECT: Although the spontaneous occurrence of an unruptured vertebral artery (VA) dissection has increasingly been recognized as a relatively common cause of stroke, and the clinical aspects of this lesion have gradually been determined, its natural course remains obscure. The main goal of this study was to clarify the management protocol for this condition by examining serial angiographic changes in patients with unruptured VA dissections. METHODS: Seventeen patients with unruptured VA dissections, including 13 men and four women, were clinically and angiographically examined between 1993 and 1998. All patients were observed using serial angiography studies. The initial angiography examinations most frequently revealed stenotic lesions (appearance of a pearl-and-string sign or string sign) in eight (47.1%) of 17 cases. In 15 cases (88.2%), changes in the lesions were evident on follow-up angiography studies. Stenotic lesions resulted in occlusion in four cases, normalization in three, and subsequent formation of an aneurysm in one case, which was treated successfully by proximal occlusion of the affected vessel performed using a detachable balloon. Occluded lesions, which were initially observed in three patients, recanalized in two patients and remained unchanged in one patient. Fusiform dilation alone was demonstrated in three patients during the initial angiography session; these lesions became normalized or were unchanged on follow-up studies. Saccular aneurysms were observed in two patients. In one of these cases, proximal ligation of the parent artery was successfully performed because of subsequent aneurysm enlargement. A double lumen, which appeared in one patient with an extradural VA dissection, became occluded. Magnetic resonance T2-weighted imaging studies revealed infarction corresponding to the posterior circulation in seven cases. During long-term observation in this series, good or excellent recovery was obtained in 14 (87.5%) of 16 patients, and moderate or severe disability in two (12.5%); one patient was lost to follow up after the second angiography study. CONCLUSIONS: A follow-up angiography study must be performed during the early stage (within approximately 3 weeks after onset of symptoms) to confirm the formation or enlargement of an aneurysm, because such conditions may be amenable to surgical treatment. Unruptured VA dissection could otherwise be treated and followed conservatively. Although the majority of dissected lesions seem likely to stabilize within a few months, as evidenced on angiography, in some cases a longer observation period is required.

Adult↗
PubMed1999

Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes.

The Ras-dependent activation of mitogen-activated protein (MAP) kinase pathways by many receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) requires the activation of Src family tyrosine kinases. Stimulation of beta2 adrenergic receptors resulted in the assembly of a protein complex containing activated c-Src and the receptor. Src recruitment was mediated by beta-arrestin, which functions as an adapter protein, binding both c-Src and the agonist-occupied receptor. beta-Arrestin 1 mutants, impaired either in c-Src binding or in the ability to target receptors to clathrin-coated pits, acted as dominant negative inhibitors of beta2 adrenergic receptor-mediated activation of the MAP kinases Erk1 and Erk2. These data suggest that beta-arrestin binding, which terminates receptor-G protein coupling, also initiates a second wave of signal transduction in which the "desensitized" receptor functions as a critical structural component of a mitogenic signaling complex.

Adrenergic beta-Agonists↗
PubMed1999

[A case of interstitial nephritis induced by a super antigen produced by methicillin-resistant Staphylococcus aureus (MRSA) presenting as acute renal failure].

We report the case of a 21-year-old man who had been developing acute renal failure with Methicillin-resistant Staphylococcus aureus (MRSA) colitis and sepsis. He was admitted for consciousness disturbance, nausea, vomiting, and diarrhea. Oliguria was also observed and his serum creatinine level was elevated to 10 mg/dl. Urinary protein was positive and an abundance of hyaline cast were seen in urinary sedimentation. Diarrhea and pyrexia were prolonged and serum C-reactive proteins were elevated, but lymphocyte and leukocyte counts temporarily decreased from the 3rd to the 6th hospital day and remained low until normalizing after the 14th day. His clinical symptoms improved with hemodialysis (HD) and effective antibiotic therapies. An MRSA strain producing toxic shock syndrome toxin-1 (TSST-1), a super antigen which specifically stimulates human V beta 2-positive T cells, was separated from his feces and blood. To ascertain the cause of his renal dysfunction, a renal biopsy was performed on the 8th day. His renal histology revealed acute interstitial nephritis with severe inflammatory cell infiltration around the medullary areas without glomerular changes. Most of the infiltrated cells were small monocytes, and lymphoid cells were rich in the interstitium. With immunohistochemical staining, over 70% of T-cells were V beta 2-positive. TSST-1-producing MRSA was detected in his blood specimen. Furthermore, V beta 2-positive T cells were accumulated in the renal intersititium, and transient lymphocytopenia was observed. These data suggested the following possible pathogenesis for interstitial nephritis: TSST-1 acts as a super antigen in the renal interstitium where major histocompatibility complex (MHC) is class-2-positive, thereby resulting in interstitial nephritis with T cell migration.

Acute Kidney Injury↗
PubMed1999

Midkine inhibits caspase-dependent apoptosis via the activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase in cultured neurons.

Midkine (MK) is a new member of the heparin-binding neurotrophic factor family. MK plays important roles in development and carcinogenesis and has several important biological effects, including promotion of neurite extension and neuronal survival. However, the mechanism by which MK exerts its neurotrophic actions on neurons has not been elucidated to date. We have established an apoptosis induction system by serum deprivation in primary neuronal cultures isolated from mouse cerebral cortices. Neuronal apoptosis induced by serum deprivation was accompanied by the activation of caspase-3. MK, when added into the culture medium, inhibited the induction of apoptosis and activation of caspase-3 in a dose-dependent manner. Extracellular signal-regulated kinase (ERK) and Akt were not activated by serum deprivation, whereas ERK and Akt were rapidly activated by addition of MK. In addition, the trophic actions of MK of suppressing apoptosis and suppressing the activation of caspase-3 were abolished by concomitant treatment with PD98059, a specific inhibitor of mitogen-activated protein kinase kinase, and with wort-mannin or LY294002, specific inhibitors of phosphatidyl-inositol 3-kinase (PI 3-kinase). These PI 3-kinase inhibitors also inhibited the activation of ERK in response to MK, demonstrating a link between ERK and the caspase-3 pathway that is modulated by the PI 3-kinase activation. These results indicate that the ERK cascade plays a central role in MK-mediated neuronal survival via inhibition of caspase-3 activation.

Androstadienes↗
PubMed1999

Midkine inhibits apoptosis via extracellular signal regulated kinase (ERK) activation in PC12 cells.

Midkine (MK) is a new member of the family of heparin-binding neurotrophic factors. MK has several important biological effects and plays an important role in the development and survival of neurons. The mechanism by which MK exerts its neurotrophic actions, however has not been sufficiently clarified. To understand the intracellular pathway activated by MK, we established an apoptosis-induction system with the neuronal cell line PC12 and studied the involvement of the mitogen-activated protein kinase (MAPK) cascade in neuroprotective actions of MK. We demonstrate here that MK rescued PC12 cells from apoptosis induced by serum deprivation in a dose-dependent manner. MK also activated extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2), which are well known as signal transducer acting downstream several receptors. PD98059, an inhibitor of MAPK kinase (MAPKK), inhibited ERK activation and also prevented the trophic effect of MK. These results indicate that MK exerts its neuroprotective actions mainly via ERK activation.

Animals↗
PubMed1998

A novel neurotrophic pyrimidine compound MS-818 enhances neurotrophic effects of basic fibroblast growth factor.

MS-818 (2-piperadino-6-methyl-5-oxo-5, 6-dihydro (7H) pyrrolo [2,3-d]pyrimidine maleate), a newly synthesized heterocyclic pyrimidine derivative, promotes neurite outgrowth in neuronal cell lines. The survival-promoting effect of MS-818 on cultured neurons isolated from mouse cortices was examined. MS-818 promoted neuronal survival by inhibiting apoptosis in a dose-dependent manner. MS-818 treatment also activated mitogen-activated protein kinase (MAPK) of the extracellular signal regulation kinase 2, as demonstrated by Western blot analysis. The MAPK activation level in the cultures treated with MS-818 was almost equivalent to that in cultures treated with nerve growth factor but was less than that in cultures treated with epidermal growth factor and basic fibroblast growth factor (bFGF). MAPK was activated within 3 min after the addition of MS-818, and its activity level returned to baseline within 120 min. Its activation was protein kinase C independent. We further investigated the effect of concurrent treatment with MS-818 and bFGF on neuronal survival. MS-818 enhanced the neuronal survival-promoting effect of bFGF in shifting the half-maximally effective dose from 2.1 ng/ml to 0.036 ng/ml in the sigmoidal dose effect of bFGF and permitted nearly maximum MAPK activation. The enhancement by MS-818 of the neuronal survival-promoting effect of bFGF was accompanied by sustained activation of MAPK to a degree that far exceeded, in magnitude and duration, the cooperative effect of MS-818 and bFGF. These results indicate that MS-818 promotes neuronal survival and enhances the neurotrophic actions of bFGF through stimulation of synchronous signals that may elevate MAPK levels within neurons.

Animals↗
PubMed1995

Highly increased insulin secretion in a patient with postprandial hypoglycemia: role of glucagon-like peptide-1 (7-36) amide.

The mechanism(s) of an inappropriate secretion of insulin is poorly understood. We report a case of reactive hypoglycemia associated with an unusually exaggerated insulin secretion. The patient, a 32-year-old man, developed frequent episodes of postprandial hypoglycemia after interferon treatment was begun for chronic type C hepatitis. Oral glucose challenge test confirmed the patient's extremely high plasma IRI response, i.e., more than 1000 microU/ml, and that of plasma C-peptide 56.9 ng/ml at 90 min, followed by symptomatic hypoglycemia (plasma glucose 34 mg/dl) at 240 min. The plasma proinsulin level also was high, but the molar ratio of immuno reactive insulin (IRI)/plasma C-peptide and IRI/proinsulin was within the normal range. Antibodies to insulin or insulin-receptor were negative. Plasma IRI response was apparently greater when the glucose was given orally than when given intravenously. The response of plasma glucagon-like-peptide (GLP)-1 to oral glucose was quite high (from baseline of 45.5 to 303.2 pmol/L) and showed a close parallel with the change in the plasma IRI concentration. The greatly enhanced insulin secretion leading to reactive hypoglycemia in this patient may therefore be attributed to the increased secretion of GLP-1.

Adult↗
PubMed1994

An adult case of Bland-White-Garland syndrome with collaterals from the bronchial artery.

We report herein an adult case of anomalous origin of the left coronary artery from the pulmonary artery (Bland-White-Garland syndrome; BWG syndrome). The patient had chest discomfort during exercise and signs of mitral regurgitation. We diagnosed him as having BWG syndrome by angiography, and performed surgical treatment. At the operation, retrograde coronary blood flow was found through the left coronary artery during aortic cross-clamping. This suggested extracardiac anastomosis from peripheral arteries to the left coronary artery. Since the collateral blood flow was considerable during aortic cross-clamping, only the left coronary artery was closed. A collateral from the left bronchial artery to the left circumflex artery was demonstrated by postoperative angiography. Cases of adults with BWG syndrome are rare, and this may be the first report of a collateral from the bronchial artery.

Adult↗
PubMed1994

Effect of glycemic control on vitamin B12 metabolism in diabetes mellitus.

To determine the effect of glycemic control on vitamin B12 (B12) metabolism in diabetes mellitus, we studied B12 metabolism in 19 diabetic patients with poor glycemic control and 15 normal individuals. The diabetic patients had significantly higher total B12 binding capacity (3303 +/- 963 pg/ml), higher serum B12 levels (1173 +/- 503 pg/ml) and unsaturated B12 binding capacity (2131 +/- 902 pg/ml) when compared with the normal controls, but there was no difference in R-binder levels and the B12 binding ratio between the two groups. During a 2-week admission to establish glycemic control, the fructosamine levels in the diabetic patients decreased from 556 to 428 mumol/l and the total B12 binding capacity as well as unsaturated B12 binding capacity were significantly improved to the normal range (P < 0.01), but serum B12 levels, R-binder levels and the B12 binding ratio were not changed. There was a significant association between serum fructosamine levels and the total B12 binding capacity in poorly controlled diabetic patients and the decrease of fructosamine was correlated significantly with the change of total B12 binding capacity and serum B12 levels in diabetic patients. These results indicate the effects of glycemic control on B12 metabolism in diabetes mellitus.

Adult↗
PubMed1994

[Autosomal dominant spinocerebellar degeneration with pigmentary retinopathy in a Japanese family].

We report a pedigree of autosomal dominant spinocerebellar degeneration associated with pigmental retinopathy. The proband is a 75-year-old man. He noticed night blindness at the age of 10 years and a diagnosis of bilateral pigmentary retinopathy was made at age 63. At the age of 65 years, he developed dysarthria and difficulty in walking. At age 69, neurological examination revealed cerebellar signs, and brain CT scans showed mild atrophy of the brain stem and cerebellum. Repeated brain CT scans revealed slight progression of the brain stem and cerebellar atrophy. Molecular genetic studies showed the absence of any mitochondrial DNA mutation at 8993. The father of the proband exhibited cerebellar signs and pigmentary retinopathy. One older brother had cerebellar signs and another had pigmentary retinopathy. To our knowledge, hereditary spinocerebellar degeneration with retinal degeneration is rare in Japan. This study is the first full report on hereditary spinocerebellar degeneration with pigmentary retinopathy in Japan, although an abstract was published by Konishi et al. We also discuss the neuropathological discordance on hereditary olivoponto-cerebellar atrophy with retinal degeneration.

Adult↗
PubMed1994

[Pick's disease in senescence].

We report two patients with Pick's disease in senescence. Patient 1 is a 78-year-old woman. She developed abnormal behavior at the age of 76 years. Neurological examination at age 76 revealed poor rapport, easy angriness, "Denkfaulheit", oral tendency, and slight dementia [WAIS (Wechsler Adult intelligence Scale) total IQ 62]. Cranial CT scan and MRI showed bilateral atrophy of the frontal and temporal lobe, especially of the temporal lobe. Patient 2 is a 73-year-old man. He developped sexual abnormal behavior and "triebhafte Hemmungslossigkeit" at the age of 71 years. Neurological examination at age 72 revealed poor rapport, lack of spontaneity, easy angriness, "Denkfaulheit", and slight dementia [WAIS total IQ 91]. Transient "stehende Redensarten" was noticed. Cranial CT scan and MRI showed bilateral atrophy of the frontal and temporal lobe, especially of the frontal lobe. To our knowledge, Pick's disease with an onset in the senescence is very rare. Pick's disease should be included in the differential diagnosis of abnormal behavior in the senescence.

Aged↗
PubMed1993

Prostacyclin analogue, beraprost, sustains recanalization duration after thrombolytic therapy in acute myocardial infarction model.

Platelets play an important role in acute reocclusion after thrombolysis in acute myocardial infarction. We tested a new antiplatelet agent, the stable prostacyclin analogue, beraprost, in the prevention of reocclusion of reperfused vessels with a combination of recombinant tissue-type plasminogen activator (rt-PA) in a canine preparation of coronary artery thrombosis superimposed on high-grade stenosis. Intravenous infusion of rt-PA (17 micrograms/kg/min for 30 min) was combined with beraprost (100, 200 or 300 ng/kg/min for 60 min) or aspirin (35 mg/kg bolus i.v. before rt-PA infusion). The reperfusion time did not differ among the 4 groups. The time from reperfusion to reocclusion (one cycle) in the rt-PA plus beraprost 200 ng/kg/min group was significantly longer than the rt-PA alone group (40 +/- 8 min vs. 9 +/- 2 min, P < 0.05) and the recanalization duration calculated as the mean time from reperfusion to reocclusion in each cycle was prolonged in the rt-PA plus beraprost 200 ng/kg/min group compared with the rt-PA alone group (48 +/- 6 min vs 18 +/- 5 min, P < 0.05) and the reocclusion time and recanalisation duration tended to be elongated in the rt-PA plus beraprost 300 ng/kg/min group, whereas those were not altered by aspirin and 100 ng/kg/min of beraprost. Bleeding time was slightly prolonged and ex vivo platelet aggregation was slightly depressed by beraprost and aspirin. Systemic blood pressure was lowered with higher doses of beraprost. Beraprost sustained coronary reperfusion time and recanalization duration at the higher doses with an optimal level, but could not eliminate reocclusion completely.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Usefulness of myocardial imaging by 123I-MIBG in assessment of diabetic neuropathy].

In diabetic patients with autonomic neuropathy, it is suggested that there is a reduced uptake of 123I-MIBG in the heart. We compared the difference of myocardial 123I-MIBG accumulation between 4 diabetic patients with triopathy and 6 patients without it. In all 10 patients, coronary angiography and 201Tl imaging (rest and 4 hours later) were performed. 123I-MIBG (111 MBq) was administered intravenously and its imaging was recorded on 15 minutes and 4 hours after injection. In all 4 cases with triopathy, 123I-MIBG imaging showed defect in apical and inferior region. In 2 out of 6 cases without triopathy, rapid clearance was noticed in apical and inferior region. There was no significant stenosis in right coronary artery and no defect in initial and delayed 201Tl images in all cases. We concluded that diabetic autonomic neuropathy in the heart was prominent in apical and inferior region and 123I-MIBG imaging might be useful for the evaluation of degrees in diabetic neuropathy.

3-Iodobenzylguanidine↗