Biomedical subjects

S Kuroda

Publications and source records attributed to S Kuroda.

At least 109 records · Page 6Linked to original sources

PubMed2000

Determination of imbalance between MMP-2 and TIMP-2 in human neuroblastoma by reverse-transcription polymerase chain reaction and its correlation with tumor progression.

BACKGROUND/PURPOSE: The matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs) have been implicated in tumor invasion and metastasis. Net matrix degradation and proteolysis depend on the critical local balance between MMPs/TIMP-2. We attempted to determine their expression balance and to evaluate its importance with tumor progression. METHODS: Expressions of MMP-2, MMP-9, and TIM P-2 mRNAs was quantified by reverse-transcription polymerase chain reaction (RT-PCR) in tumor tissues from 25 neuroblastoma patients. RESULTS: MMP-2, MMP-9, and TIMP-2 expression was observed in all the samples but with different trends. Increased expressions of MMP-2 mRNA was evident in advanced stages (Evans' stage III and IV; P = .02; unpaired ttest), and in patients who died of progressive disease (P = .0001). Whereas, the expressions of MMP-9 and TIMP-2 had no such significant association with clinical stages and prognosis. The ratio of MMP-2/TIMP-2 mRNAs was significantly higher in the advanced stages versus early stages (mean +/- SD = 1.66+/-0.65 and 1.11+/-0.34, respectively; P = .02) and in patients who died of progressive disease versus alive patients (mean = 2.13+/-0.78 and 1.21+/-0.36, respectively; P = .0006). CONCLUSIONS: Coexpression of MMPs and TIMP-2 in neuroblastoma indicates the need to evaluate their expression balance. Significantly higher expression of MMP-2 mRNA and increased ratio of MMP-2 and TIMP-2 mRNAs in advanced stages or patients who have died of progressive disease suggests an association between elevated MMP-2 expression and poor prognosis. To establish the role of enzyme to inhibitor mRNA ratio as a reliable predictor, cohort studies with significant number of cases may be carried out.

Base Sequence↗

PubMed2000

A low dose of lithium chloride selectively induces Fos protein in the central nucleus of the amygdala of rat brain.

1. Lithium is a very effective treatment for mood disorders. To elucidate the neural substrates of the mood stabilizing actions of lithium, in the present study the authors investigated the effects of a low dose of lithium on regional expression of Fos protein. 2. The administrations of a high dose of lithium chloride (100 mg/kg) induced Fos in widespread areas of the rat brain. In contrast, administration of a low dose of lithium chloride, equivalent to a therapeutic dose in humans, induced Fos only in the central nucleus of the amygdala. 3. These results demonstrate that the central nucleus of the amygdala plays important role in the neural framework that is responsible for the mood-stabilizing effect of lithium.

Amygdala↗

PubMed2000

Clozapine- and olanzapine-induced Fos expression in the rat medial prefrontal cortex is mediated by beta-adrenoceptors.

The atypical neuroleptics, clozapine and olanzapine, have superior therapeutic efficacy against the negative symptoms of schizophrenia, compared with the typical neuroleptics. Recently, it has been suggested that the ability of clozapine and olanzapine to induce Fos expression in the medial prefrontal cortex (mPFC), contribute to their therapeutic efficacy. However, the mechanisms underlying the neuropharmacological effects of clozapine and olanzapine in the mPFC remain elusive. In the present study, we demonstrate that clozapine- and olanzapine-induced Fos expression in the mPFC are inhibited by propranolol. We also show that clozapine and olanzapine induce Fos expression in the locus coeruleus. These results suggest that clozapine and olanzapine increase noradrenaline release by stimulating noradrenergic neuronal activity in the locus coeruleus and, consequently, increased noradrenaline induce Fos expression in the mPFC via beta-adrenergic receptors. This postulated sequence may be one of mechanisms by which clozapine-like atypical neuroleptics are more effective for the negative symptoms of schizophrenia.

Adrenergic beta-Antagonists↗

PubMed2000

Carbamazepine suppresses methamphetamine-induced Fos expression in a regionally specific manner in the rat brain. Possible neural substrates responsible for antimanic effects of mood stabilizers.

Carbamazepine (CBZ) has been widely used for treatment of manic states. Because amphetamine produces effects in humans similar to those of idiopathic mania, acute methamphetamine administration could serve as a model of this condition. To elucidate the neurobiological substrates responsible for the antimanic effects of carbamazepine, this study investigated the effects of chronic carbamazepine administration on regional Fos protein expression induced by a single dose of methamphetamine (2mg/kg). Chronic treatment with CBZ (0.25% in food for 7 days, followed by 0.5% for 7 days; final mean serum carbamazepine concentration: 4.09 +/- 0.34 microg/ml) significantly attenuated the number of Fos-like immunoreactivity-positive nuclei induced by methamphetamine administration in the core of the nucleus accumbens and the caudate/putamen. The results indicate these brain regions are involved in the antimanic effects of carbamazepine.

Amphetamine-Related Disorders↗

PubMed2000

Novel adenosine A1 receptor antagonists. Synthesis and structure-activity relationships of a novel series of 3-(2-cyclohexenyl-3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5 -a]pyridines.

A novel series of 3-(2-cyclohexenyl-3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazol o[1,5-a]pyridines was synthesized and evaluated for in vitro adenosine A1 and A2A receptor binding activities. Most of the cyclohexenyl derivatives (7a-e, 8a-s) were found to be potent adenosine A1 receptor antagonists. In a series of analogues of FR166124 (3a), alcohol 7c, nitrile 7e and amide derivatives (7d, 8c, 8r) were found to be more potent A1 antagonists with higher A2A/A1 selectivity than FR166124. Amongst them, 8r showed considerable water solubility (33.3 mg/mL), but lower than that of the sodium salt of FR166124 (> 200 mg/mL). Additionally, FR166124 had strong diuretic activity by both p.o. and iv administration in rats (minimum effective dose=0.1 and 0.032 mg/kg, respectively).

Animals↗

PubMed2000

Relationship between oxidative stress and apoE phenotype in Alzheimer's disease.

OBJECTIVE: To investigate the relationship between oxidative stress and apoE phenotype in dementia of Alzheimer type (DAT). MATERIAL AND METHODS: Hydroxyl radical content in blood, superoxide dismutase (SOD) activity in red blood cells (RBC) and plasma, Cu,Zn-SOD protein content in RBC, and apoE phenotype were determined in 24 DAT patients and 25 controls. RESULTS: DAT patients with the apoE4 phenotype showed higher hydroxyl radical levels than DAT patients without the apoE4 phenotype or controls. SOD activities and Cu,Zn-SOD protein levels in RBC of DAT patients with and without the apoE4 phenotype showed no significant differences, but values in both patient groups were lower than in controls. The apoE4 phenotype was more prevalent in DAT patients than in controls. DAT patients with the apoE4 phenotype were younger at disease onset than DAT patients without the apoE4 phenotype. CONCLUSION: Our findings suggest that apoE4 and SOD individually influence oxidative stress in DAT.

Aged↗

PubMed2000

Elevation of neuron-specific enolase in serum and cerebrospinal fluid of early stage Creutzfeldt-Jakob disease.

OBJECTIVE: To investigate the levels of neuron-specific enolase (NSE) in serum and cerebrospinal fluid (CSF) of patients with early stage Creutzfeldt-Jakob disease (CJD). METHODS: The levels of NSE in serum and CSF were examined in 6 cases with CJD patients. The levels of NSE in CSF were measured in 8 age matched control patients with other neurological diseases and the levels of serum NSE were also measured in another 8 age matched control patients with other neurological diseases. The groups of 8 age matched control patients consisted of 1 same patient and 7 different patients in the 2 control groups both for serum and CSF. RESULTS: The level of serum NSE in CJD (17.3 +/- 7.0 ng/ml, mean +/- SD) was significantly higher than that of controls (6.5 +/- 1.6) (P < 0.02) as was the case in CSF (79.3 +/- 53.3 ng/ml) vs (9.6 +/- 2.9) (P < 0.03). CONCLUSION: Although mean NSE levels of CJD were higher in CSF than in the serum, there still is a case with higher serum NSE level than CSF. These results suggest that the mechanism of elevation of serum NSE may not be a simple leakage from CSF, and that the measurement of serum NSE level may be useful for diagnosis of early stage CJD.

Aged↗

PubMed2000

Surgical effects of combined trabeculotomy and sinusotomy compared to trabeculotomy alone.

PURPOSE: To elucidate long-term surgical results and problems of combined trabeculotomy and sinusotomy in comparison with trabeculotomy alone. METHODS: The study included 91 glaucomatous eyes in 57 patients with primary open angle glaucoma, who underwent either combined trabeculotomy and sinusotomy (40 eyes) or trabeculotomy alone (51 eyes). The mean follow-up period (+/-standard deviation) was 46.1+/-10.4 months (range: 30 to 60 months). RESULTS: At the final examination, in 37 (93%) of the 40 eyes after combined trabeculotomy and sinusotomy and in 40 (78%) of the 51 eyes after trabeculotomy alone, intraocular pressures were well controlled. The mean intraocular pressures at the end of the first postoperative year were 15.6+/-3.0 mmHg in the 40 eyes after the combined procedure, and 17.8+/-3.1 mmHg in the 51 eyes after trabeculotomy alone (p=0.0001, unpaired t-test). Complications included Descemet's membrane detachment in 1 eye (3%) and 4 eyes (8%), and transient elevation of intraocular pressure to higher than 30 mmHg (IOP spike) in 6 eyes (15%) and 11 eyes (22%), respectively, after the combined procedure and trabeculotomy alone. CONCLUSION: Combined trabeculotomy and sinusotomy is a useful surgical modality for the treatment of primary open angle glaucoma to obtain lower intraocular pressure levels than those after trabeculotomy alone.

Female↗

PubMed2000

Phosphorylation of ERM proteins at filopodia induced by Cdc42.

BACKGROUND: ERM (ezrin, radixin, and moesin) proteins function as membrane-cytoskeletal linkers, and are known to be localized at filopodia and microvilli-like structures. We have shown that Rho-associated kinase (Rho-kinase)/ROKalpha/ROCK II phosphorylates moesin at Thr-558 at the lower stream of Rho, and the phosphorylation is crucial to the formation of microvilli-like structures (Oshiro, N., Fukata, Y. & Kaibuchi, K. (1998) Phosphorylation of moesin by Rho-associated kinase (Rho-kinase) plays a crucial role in the formation of microvilli-like structures. J. Biol. Chem. 273, 34663- 34666). However, the role of ERM proteins in the formation of filopodia is less well characterized. RESULTS: Here we examined the phosphorylation state of ERM during filopodia formation induced by Cdc42 using the antibody recognizing ERM proteins phosphorylated at COOH (C)-terminal threonine. When NIH 3T3 cells were transfected with constitutively active Cdc42 (Cdc42V12), filopodia formation was induced and phosphorylation of ERM at C-terminal threonine was observed at the tip of filopodia, while the phosphorylation levels of ERM were lower and phosphorylated ERM was distributed throughout the cytoplasm in the control cells. We also showed that Myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) which has been identified as an effector of Cdc42, phosphorylated moesin at C-terminal threonine in a cell-free system. Coexpression of the dominant negative form of MRCK inhibited both the formation of filopodia and accumulation of C-terminal threonine-phosphorylated ERM proteins at filopodia induced by Cdc42V12. CONCLUSION: The formation of filopodia induced by Cdc42 is accompanied by phosphorylation of ERM proteins, and MRCK is a candidate for the kinase that phosphorylates ERM proteins at filopodia.

3T3 Cells↗

PubMed2000

An autopsy case of postencephalitic parkinsonism of von Economo type: some new observations concerning neurofibrillary tangles and astrocytic tangles.

An autopsied case of postencephalitic parkinsonism of von Economo type with a 71-year duration is reported. Several cases of postencephalitic parkinsonism of von Economo type have been reported in Japan but this is the first reported case from western Japan. The patient was a Japanese man who was 74 years of age at the time of death. He developed encephalitis of unknown etiology at the age of 3 years. The first symptom was antisocial behavior, which developed at 30 years of age. At the age of 40 years, the patient showed progressive parkinsonism. Neuropathological findings disclosed marked neuronal loss with gliosis in the substantia nigra, locus ceruleus, and raphe nuclei, as well as the appearance of neurofibrillary tangles in the aforementioned areas. There were also widespread tuft-shaped astrocytes (Tu-SA) in the central nervous system, including the thalamus. Tuft-shaped astrocytes are considered to represent non-reactive astrocytes because the distributions of neurofibrillary tangles (NFT) and Tu-SA are clearly different. Therefore, the primary astrocytic lesions in postencephalitic parkinsonism of von Economo type may be more widespread. Ultrastructurally, the Tu-SA consisted of straight filaments, 15 nm in width, which formed tight bundles. Ultrastructurally, NFF in this case revealed paired helical filaments but straight filaments, 15 nm in width, which were also found in the neurons of the substantia nigra.

Aged↗

PubMed2000

Patent ductus venosus with a hypoplastic intrahepatic portal system presenting intrapulmonary shunt: a case treated with banding of the ductus venosus.

A case of patent ductus venosus (PDV) presenting intrapulmonary shunting is described. Although retrograde venography of ductus venosus showed few intrahepatic branches, banding of PDV resulted in increased intrahepatic portal branches and disappearance of symptoms 10 months after the operation. Banding of the ductus venosus may be effective in PDV even with hypoplastic intrahepatic portal system.

Child↗

PubMed2000

Changes in E-cadherin associated with cytoplasmic molecules in well and poorly differentiated endometrial cancer.

E-cadherin function is thought to be impaired in epithelial cancer. To investigate the alterations in E-cadherin associated with cytoplasmic molecules including alpha-catenin, beta-catenin, gamma-catenin, p120CAS, and IQGAP1 in various endometrial cancers with different degree of differentiation, we examined the localization and expression of E-cadherin and cytoplasmic molecules in 30 cases of both well and poorly differentiated endometrioid adenocarcinomas, using immunofluorescence and immunoblotting techniques. E-cadherin and cytoplasmic molecules demonstrated linear staining at the cell boundaries in normal endometrium. In all 20 cases with well differentiated adenocarcinomas, alpha-catenin and IQGAP1 disappeared from the cell adhesive sites, but other cytoplasmic molecules were co-localized with E-cadherin along the cell boundaries. In all 10 cases with poorly differentiated adenocarcinomas, E-cadherin and cytoplasmic molecules accumulated as large aggregates along cell adhesive sites, and the localization of IQGAP1 differed from those of other cytoplasmic molecules. The expression of these molecules in all 20 cases with well differentiated adenocarcinomas decreased or was lost in Triton-insoluble fraction, in comparison with the findings for all cases with normal endometrium or poorly differentiated adenocarcinomas. These results suggested that each alteration in E-cadherin associated with cytoplasmic molecules may play a different role in E-cadherin dysfunction between well and poorly differentiated adenocarcinomas.

Adenocarcinoma↗

PubMed2000

Dental follicle cell-conditioned medium enhances the formation of osteoclast-like multinucleated cells.

An influx of mononuclear cells and the subsequent increase of osteoclasts around tooth germs suggests that the dental follicle (DF) regulates or influences bone resorption required for tooth eruption. In order to study the effects of DF cell products on osteoclast formation during tooth eruption, a conditioned medium (CM) was created in which DF cells were added to mouse bone marrow cultures. Tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like multinucleated cells were formed in the presence of 10 nM 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The CM, dose-dependently, stimulated the formation of TRAP-positive cells in the presence of 1,25(OH)2D3 for 14 days culture. The number of these cells decreased due to degradation in the control culture. A semi-solid methylcellulose assay in the presence of CM showed little expression of colony-stimulating activity. These results suggest that the DF cells of a developing tooth produce factor(s) that enhance osteoclast formation and bone resorption necessary for tooth eruption.

Acid Phosphatase↗

PubMed2000

Novel presenilin-1 mutation with widespread cortical amyloid deposition but limited cerebral amyloid angiopathy.

OBJECTIVE: To clarify the phenotypic heterogeneity in deposition of amyloid beta (Abeta) in the parenchyma and in cerebral vessels of the brains of the patients having presenilin-1 (PS1) mutations. Mutations in PS1 induce increased production of Abeta42(43), resulting in an enhanced overall deposition of Abeta protein within the cerebral cortex. METHODS: Sequence analysis of the PS1 gene of DNA from patients with early onset Alzheimer's disease, and immunostaining of brain tissues by end specific monoclonal antibodies against Abeta. RESULTS: Sequence analysis disclosed a novel mutation (N405S) in the PS1 gene in a Japanese patient with early-onset Alzheimer's disease. Postmortem examination of one patient with N405S showed limited cerebral amyloid angiopathy, whereas postmortem examination of another Japanese patient with Alzheimer's disease with the E184D mutation disclosed severe cerebral amyloid angiopathy. The brains of both patients showed widespread neuritic plaques, neurofibrillary tangles, and neuronal loss. Immunostaining showed that Abeta42 was predominant over Abeta40 in neuritic plaques in both patients, whereas Abeta40 was found to be predominant over Abeta42 in cerebral amyloid angiopathy in the patient with E184D. However, most cortical vessels of the patient with N405S were not reactive with either of the antibodies. CONCLUSION: The N405S mutation of PS1 is a major determinant of cortical Abeta deposition but not cerebral amyloid angiopathy in Alzheimer's disease.

Alzheimer Disease↗

PubMed2000

Exacerbation of renal failure due to hypothyroidism in a patient with ischemic nephropathy.

A case of acute-on-chronic renal failure in a 70-year-old woman with ischemic nephropathy and primary hypothyroidism is presented. Her renal function became progressively worse as the level of serum creatinine increased from 283 to 628 micromol/l (3.2-7.1 mg/dl) within 8 months. Her thyroid function had been normal before the exacerbation of renal failure, but it was markedly reduced with a marked elevation of serum thyroid-stimulating hormone. Thyroid hormone replacement therapy resulted in rapid improvement of the renal function to 159 micromol/l (1.8 mg/dl) of serum creatinine. The development of primary hypothyroidism seemed to worsen the already impaired renal function in this case. We suggest the assessment of thyroid function in patients with unexplained deterioration of renal failure.

Aged↗

PubMed2000

Prevalence of renal artery stenosis in autopsy patients with stroke.

BACKGROUND AND PURPOSE: Atherosclerotic renal artery stenosis commonly exists as one manifestation of more generalized atherosclerosis. It is a progressive but potentially curable disorder. Thus, information on renal artery involvement in atherosclerotic diseases could be important. We investigated the prevalence of renal artery stenosis in autopsied patients with stroke over 40 years of age. METHODS: From 2167 consecutive autopsy patients who died between 1980 and 1997, we studied 346 cases of mean age of 69+/-11 years with clinical evidence of stroke. RESULTS: Atherosclerotic renal artery stenosis (>/=75% luminal area narrowing) was found in 36 patients (10.4%). Patients with renal artery stenosis were older and had worse renal function. Renal artery stenosis was found in 14.7%, 28.6%, and 23.9% of patients with hypertension, renal insufficiency, and aortic aneurysm, respectively. Extracranial carotid artery stenosis (>50% luminal area narrowing) was found in 101 patients (29.2%). Of the 346 stroke patients, 256 had a history of brain infarction. In patients with brain infarction, renal artery stenosis was found in 31 (12.1%) and carotid stenosis was found in 81 (33.6%). Patients with carotid artery stenosis were more likely to have renal artery stenosis than patients without carotid artery stenosis (24.4% versus 5.9%, P<0.0001). Multiple logistic regression analysis identified renal insufficiency, hypertension, female gender, and presence of carotid artery stenosis as independent predictors of renal artery stenosis in patients with brain infarction. CONCLUSIONS: These data reveal that atherosclerotic renal artery stenosis is common in patients with stroke, especially in those with brain infarction.

Aged↗

PubMed2000

Linkage of familial moyamoya disease (spontaneous occlusion of the circle of Willis) to chromosome 17q25.

BACKGROUND AND PURPOSE: Moyamoya disease is a cerebrovascular disease of unknown cause that mainly affects Japanese children. The incidence of familial occurrence accounts for 9% of cases. The characteristic lesions of moyamoya disease are occasionally seen in neurofibromatosis type 1, of which the causative gene (NF1) has been assigned to chromosome 17q11.2. METHODS: To determine whether a gene related to moyamoya disease is located on chromosome 17, we conducted microsatellite linkage analyses on 24 families containing 56 patients with moyamoya disease. Leukocyte DNA extracted from the family members was subjected to polymerase chain reaction for a total of 22 microsatellite markers on chromosome 17. The amplified polymerase chain reaction fragments were analyzed with GeneScan on an automated sequencer. RESULTS: Two-point linkage analysis gave a maximum log(10) odds (LOD) score of 3.11 at the recombination fraction of 0.00 for the marker at locus D17S939. The affected pedigree member method also showed a significantly low P value (<1. 0x10(-5)) for the 5 adjacent markers at 17q25. Multipoint linkage analysis also indicated that the disease gene is contained within the 9-cM region of D17S785 to D17S836, with a maximum LOD score of 4. 58. CONCLUSIONS: A gene for familial moyamoya disease is located on chromosome 17q25.

Cerebral Angiography↗

PubMed2000

Synaptic development is controlled in the periactive zones of Drosophila synapses.

A cell-adhesion molecule fasciclin 2 (FAS2), which is required for synaptic growth and still life (SIF), an activator of RAC, were found to localize in the surrounding region of the active zone, defining the periactive zone in Drosophila neuromuscular synapses. BetaPS integrin and discs large (DLG), both involved in synaptic development, also decorated the zone. However, shibire (SHI), the Drosophila dynamin that regulates endocytosis, was found in the distinct region. Mutant analyses showed that sif genetically interacted with Fas2 in synaptic growth and that the proper localization of SIF required FAS2, suggesting that they are components in related signaling pathways that locally function in the periactive zones. We propose that neurotransmission and synaptic growth are primarily regulated in segregated subcellular spaces, active zones and periactive zones, respectively.

Animals↗