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Biomedical subjects

N Yamamoto

Publications and source records attributed to N Yamamoto.

At least 145 records · Page 8Linked to original sources
PubMed2001

Brain structures of a medaka mutant, el (eyeless), in which eye vesicles do not evaginate.

Eye development and brain structures of a mutant teleost fish were investigated. The el (eyeless) mutation in medaka (Oryzias latipes) is recessive and affects eye formation; in the most severe cases, it results in the absence of eyes. Developmental studies revealed that normal eyeballs are not formed in the el mutant embryos, but small optic cup-like structures differentiate in situ in the walls of the prosencephalon without evagination. The anophthalmic el homozygous fish hatched normally, although they did not respond behaviorally to visual stimuli. A small fraction of these fish grew to adulthood. In the adult anophthalmic el homozygous fish, the brain exhibited abnormalities in several subdivisions. A pair of small abnormal protrusions was observed on the surface of the ventral telencephalon and preoptic area. Immunocytochemistry using a rhodopsin monoclonal antibody showed that opsin-positive cells were present in the abnormal structures. Bodian staining showed that the optic nerves were present near the abnormal structures, although the number of optic nerve fibers was extremely small. The optic tectum was extremely small, and the thickness of the stratum opticum and stratum fibrosum et griseum superficiale was reduced. These behavioral and morphological observations suggest that the adult anophthalmic el homozygous fish are functionally blind, although small retina-like structures were partially differentiated and persisted in the adult fish brain. Moreover, the adult anophthalmic el homozygous fish were infertile, and the sizes of the hypophysis and the hypothalamus were reduced. Thus, the el mutation affects not only the brain structures that are related to the visual system but also those related to the reproductive system.

Animals↗
PubMed2001

Effect of emedastine difumarate on CC chemokine-elicited eosinophil migration.

Emedastine difumarate (emedastine) is an antiallergic drug found among the derivatives which has a series of benzimidazole frames. It has been reported that emedastine can significantly inhibit the migration of eosinophils elicited by classical chemoattractants, including LTB4 or PAF. However, the effect of emedastine on the selective migration of eosinophils that have been stimulated with CC chemokines has not been examined. Emedastine at concentrations of 10 nM or higher strongly inhibited the eosinophil migration elicited by CC chemokines, including eotaxin, RANTES and MCP-3. Preincubation of the eosinophils with emedastine did not alter the expression of the CCR3 receptor, although a decrease in the concentration of intracellular calcium ions was observed after stimulation with 100 ng/ml of eotaxin. Herbimycin A, genistein, staurosporin and emedastine were all able to inhibit the eotaxin-elicited migration. Tyrosine kinase activity in the cytosol supernatant of eosinophils obtained after stimulation with eotaxin significantly decreased when the eosinophils were preincubated with emedastine. In addition, protein kinase A and protein kinase C activities in eotaxin-stimulated EoL-1 cell supernatants decreased significantly with emedastine pretreatment. These findings suggest that emedastine inhibits CC chemokine-elicited eosinophil migration by decreasing the activities of tyrosine kinase or protein kinases but does not alter CCR3 expression.

Anti-Allergic Agents↗
PubMed2001

Fiber connections of the nucleus isthmi in the carp (Cyprinus carpio) and tilapia (Oreochromis niloticus).

The nucleus pretectalis (NP) is a prominent nucleus in the percomorph pretectum and has been shown to project to the nucleus isthmi in the filefish by an HRP tract-tracing method [Ito et al., 1981], but a homologous nucleus to the NP is apparently lacking in ostariophysans. The present study examined fiber connections of the nucleus isthmi in an ostariophysan teleost, the carp (Cyprinidae, Cyprinus carpio), to identify a nucleus homologous to the percomorph nucleus pretectalis. Identical studies in a percomorph tilapia (Cichlidae, Oreochromis niloticus) were also performed. Injections of biotinylated dextran amine (BDA) or biocytin to the carp nucleus isthmi labeled cells in the ipsilateral optic tectum and nucleus ruber of Goldstein [1905]. Labeled tectal neurons were located in the stratum periventriculare (SPV) and the stratum fibrosum et griseum superficiale (SFGS). The somata in the SPV were pyriform and those in the SFGS were fusiform. No labeled cells were found in the pretectum. Labeled terminals were seen in the ipsilateral nucleus pretectalis superficialis pars parvocellularis (PSp), optic tectum, and bilateral nucleus ruber. Terminals in the nucleus ruber appear to come from tectal neurons in the SFGS labeled by isthmic injections. Thus the nucleus isthmi has reciprocal fiber connections with the ipsilateral optic tectum, receives projections from the ipsilateral nucleus ruber, and projects to the ipsilateral PSp. The nucleus pretectalis homologue is apparently absent in the carp. Studies in tilapia showed that the nucleus isthmi receives bilateral projections from the NP and optic tectum. In addition, the present study revealed a previously unknown afferent from the nucleus ruber to the percomorph nucleus isthmi. The tilapia nucleus isthmi projects to the same targets as in the carp. Isthmic projection neurons in the tilapia optic tectum were located in the SPV and pyriform with a similar shape to the carp SPV neurons that project to the nucleus isthmi. No labeled cells were found in the SFGS of tilapia optic tectum. The fusiform neurons in the SFGS of the carp optic tectum possess various hodological similarities with the NP and may correspond to the NP neurons of percomorphs.

Animals↗
PubMed2001

Protective effect of FR183998, a Na+/H+ exchange inhibitor, against postischemic injury after normothermic and prolonged hypothermic ischemia in isolated perfused rat hearts.

Inhibition of Na+/H+ exchanger has been reported to protect hearts from ischemia and reperfusion injury. However, the effect of Na+/H+ exchange inhibition on hypothermic ischemic injury has not been extensively studied and the results are inconsistent. The purpose of this study was to investigate whether inhibition of Na+/H+ exchange with FR183998 (5-(2,5-dichlorothiphen-3-yl)-3-[(2-dimethylaminoethyl)carbamoyl]benzoylguanidine dihydrochloride), a potent Na+/H+ exchange inhibitor, would show protective effects against postischemic cardiac dysfunction after hypothermic as well as normothermic ischemia and furthermore, after hypothermic cardioplegic arrest in isolated rat hearts. FR183998 (3.2 x 10(-8)-3.2 x 10(-7) M) improved post-ischemic recovery of left ventricular developed pressure and suppressed the increase of left ventricular end diastolic pressure in a dose-dependent manner, after not only 45 min of normothermic ischemia but also 6 h of hypothermic ischemia. Furthermore, FRI 83998 (10(-7)-10(-6) M) significantly reduced creatine kinase release during reperfusion after 3 h of hypothermic ischemia with cardioplegia. These results indicate that FR183998 has a potent protective effect on postischemic cardiac dysfunction after normothermic and hypothermic ischemia, and also on reperfusion injury after hypothermic cardioplegic arrest, suggesting that its effect would be additive to cardioplegia.

Animals↗
PubMed2001

Luminometric assay of platelet activation in 96-well microplate.

As of today, no practical method for large-scale functional anti-thrombosis agent screening exists. Based on the phenomenon that platelet activation results in the release of ATP from dense granules, we report the development and optimization of a 96-well microplate luciferase assay to assess platelet activation via luminescence detection of the released ATP. In addition, the assessment of re-calcification-induced clotting of citrated platelet-rich plasma (PRP) is also possible. Collagen, thrombin, U46619, and ADP were shown to induce platelet activation in a concentration- and time-dependent manner The assay is applicable to PRP, washed platelets, and whole blood. Fundamentally, this is an ideal protocol for screening large numbers of anti-thrombotic drugs because of its sensitivity and the low amount of platelets required to detect simultaneous platelet activation.

Adenosine Diphosphate↗
PubMed2001

Frequent allelic loss/imbalance on the short arm of chromosome 3 in tongue cancer.

Frequent allelic imbalances including loss of heterozygosity (LOH) and microsatellite instability (MSI) on the short arm of chromosome 3 (3p) have been found in several types of human cancer. This study was designed to identify the tumor suppressor locus (or loci) on 3p associated with tongue squamous cell carcinoma (SCC). Among 16 patients with tongue SCC tested, 7 (44%) of 16 informative cases showed LOH at one or more loci. Deletion mapping of these 16 tumors revealed two discrete, commonly deleted regions on the chromosome arm. Our data support the notion that tumor suppressor gene(s) contributing to the progression of tongue squamous cell carcinoma reside on 3p24 and 3p25.

Carcinoma, Squamous Cell↗
PubMed2001

Analysis of a role for p16/CDKN2 expression and methylation patterns in human oral squamous cell carcinoma.

The p16/CDKN2 (cyclin dependent kinase number 2) gene is known to be one of the negative regulators of the cell cycle. Aberrant 5'CpG island methylation is one of the most important mechanisms of p16/CDKN2 gene promoter region alteration. We studied 8 oral squamous cell carcinoma cell lines and 25 primary tumor tissues for the p16/CDKN2 gene and its expression by PCR-SSCP, MSP, RT-PCR, and immunohistochemical methods to determine the mechanism and the potential biological significance of p16/CDKN2 gene inactivation. In primary tumors, no p16/CDKN2 gene mutations were found by PCR-SSCP. However, hypermethylation of the CpG sites of p16/CDKN2 gene was observed in 48% (12/25) cases of primary tumors and in 50% (4/8) of cell lines. To verify the p16 mRNA expression, we employed RT-PCR and observed decreased or lacked p16 mRNA in 44% (11/25) of primary tumor tissues. In addition, hypermethylation was observed in 6 of the above 11 cases (55%). An immunohistochemistry assay was also performed with the primary tumor tissues, and a semi-quantitative method was used to evaluate the staining intensity of p16 protein. We observed 52% (13/25) negative nuclear staining. When we compared these results with clinicopathological stages, there was no statistical significance. These findings suggest that hypermethylation of p16/CDKN2 promoter region may be associated with p16/CDKN2 gene alteration.

Aged↗
PubMed2001

Allelic imbalance on the long arm of chromosome 21 in human oral squamous cell carcinoma: relationship between allelic imbalances (LOH and MSI) and clinicopathologic features.

Frequent allelic imbalances, including loss of heterozygosity (LOH) and microsatellite instability (MSI), have been found on the long arm of chromosome 21 (21q) in several types of human cancer. This study was designed to identify the tumor suppressor locus (or loci) associated with oral squamous cell carcinoma (SCC) on 21q. In order to understand the details of genetic alterations on chromosome 21, we performed polymerase chain reaction analysis of microsatellite polymorphisms corresponding to ten loci on this chromosome. We examined forty primary tumor tissues, forty corresponding normal tissues, and seven lymph node metastatic tissues. We identified novel tumor suppressor loci in this region in primary oral SCCs. To further determine the role of 21q deletions in oral cavity carcinogenesis, forty oral SCCs were examined for allelic imbalances (LOH or MSI) at 21q using ten microsatellite markers. Among these forty patients, twenty-six (65%) showed LOH at one or more loci. Deletion mapping of these tumors revealed four discrete, commonly deleted regions on the chromosome arm. Furthermore, we detected MSI in seventeen of those tested cases (42.5%). We compared our results with the clinicopathologic features. A number of sites displaying LOH at 21q could be detected in early stage lesions, and the frequencies of LOH tended to be higher in later clinical stages, but no statistical correlation was observed. Our results strongly suggest that allelic imbalances on 21q are involved in the development of oral SCC and that at least four different putative tumor suppressor genes contributing to the pathogenesis of this disease are present on 21q. Furthermore, allelic loss on 21q appears to be a useful indicator for evaluating the malignancy and prognosis of oral SCC, because the LOH of recurrent cases was more frequent than that of non-recurrent ones.

Adult↗
PubMed2001

[Usefulness of ambulatory adjuvant chemotherapy with low-dose epirubicin in patients with axially-node positive breast cancer: Chiba Epirubicin Cooperative Study Group].

We evaluated the usefulness of adjuvant chemotherapy with low-dose epirubicin (EPI) as a key drug in patients with axially-node positive breast cancer. All the 24 patients who were entered in the study between January 1991 and December 1992 were shown histologically to have more than 4 axially-node involvement and underwent curable resection for the breast lesions. Twenty mg/m2 of EPI was administered intravenously every 4 weeks as ambulatory treatment for 1 year and 5-fluorouracil (5-FU) and tamoxifen (TAM) were concomitantly administered at a dose of 150 mg/day and 20-40 mg/day, respectively, daily for 2 years. The median follow-up period was 70 months with a 55.1% 5-year relapse-free survival and 67.4% 5-year survival rate. One patient developed Grade 3 nausea.vomiting, anorexia and general fatigue; however, the other toxicities were mild, such as Grade 1 leukopenia, liver dysfunction, nausea.vomiting, anorexia and general fatigue. This adjuvant therapy with low-dose EPI was safely administered to outpatients, and is considered to be useful for the treatment of axially-node positive breast cancer.

Adult↗
PubMed2001

Quantitative analyses of messenger RNA of human endogenous retrovirus in patients with systemic lupus erythematosus.

OBJECTIVE: Human endogenous retrovirus (HERV) has emerged as a possible causative agent of systemic lupus erythematosus (SLE). To investigate the role of HERV in the etiology of SLE, we performed quantitative analyses of messenger RNA (mRNA) of the HERV clone 4-1 in patients with SLE. METHODS: Reverse transcriptase (RT)-polymerase chain reaction (PCR) and real-time quantitative PCR (RQ-PCR; TaqMan methodology) were used in this experiment. RESULTS: The quantities of mRNA of the HERV clone 4-1 gag region in patients with SLE were significantly higher than in healthy controls, and the amounts of such mRNA in the patients were decreased by steroid treatment. CONCLUSION: These phenomena may be related to the production of viral components derived from HERV clone 4-1 and contribute to the pathogenesis of SLE; studies using a larger number of patients are required to confirm these points.

Adult↗
PubMed2001

[Metastatic liver tumor arising from prostate cancer following transurethral resection of the prostate--a report of two cases].

We herein present a report of metastatic liver tumor arising from prostate cancer following transurethral resection of the prostate (TUR) in two patients. The two patients were diagnosed as having moderately differentiated prostate adenocarcinoma, either stage C or B2, and underwent hormonal and/or radiation therapy. TUR was performed due to the patients' complaints of urinary outlet obstruction. Liver metastasis, without evidence of bone or pulmonary metastasis, was then noted 23 and 5 months later in the patients with stage C and B2 prostate cancer, respectively. It is possible that the process of TUR is related to the release of tumor cells from the prostate into the systemic circulation and involved in the development of liver metastasis.

Adenocarcinoma↗
PubMed2001

Surgical treatment of an aneurysm of the aberrant right subclavian artery involving an aortic arch aneurysm and coronary artery disease.

A 55-year-old man presented with clinical signs of an aortic arch aneurysm. Angiography, MRI and CT demonstrated an aortic arch aneurysm and an aneurysm of the aberrant right subclavian artery. Coronary angiography revealed 95% stenosis in the right coronary artery. Right common carotid artery-right subclavian artery bypass, arch graft replacement and coronary artery bypass grafting were performed successfully. The use of internal shunt tube, hypothermic circulatory arrest and selective cerebral perfusion were useful methods in prevention of cerebral ischemia during surgical reconstruction of the aortic arch. To our knowledge, this is the first report in the literature of a successfully managed case with an aneurysm of an aberrant right subclavian artery involving an aortic arch aneurysm and coronary artery disease.

Aneurysm↗
PubMed2001

Hyperactivity of 99mTc-HMPAO within 6 hours in patients with acute ischemic stroke.

UNLABELLED: Intraarterial thrombolytic therapy has been used recently for treatment of acute ischemic stroke within 6 h after onset. Although hypoactivity of 99mTc-hexamethylpropyleneamine oxime (HMPAO) in stroke has been well documented, hyperactivity of HMPAO has not been evaluated in sufficient detail. The purpose of this study was to evaluate the incidence and clinical importance of hyperactivity of HMPAO in management of patients with acute ischemic stroke. METHODS: We retrospectively investigated HMPAO SPECT in 90 patients with acute ischemic stroke within 6 h after onset. The lesion-to-contralateral radioactivity ratios (L/Cs) were calculated on the SPECT images before treatment and were compared with the imaging results of CT or MRI (or both). RESULTS: Hyperactivity of HMPAO, accompanied by surrounding hypoactivity, was observed in 6 of 90 patients (7%) within 6 h after onset. The L/Cs ranged from 1.17 to 2.95. Two patients showed hyperactivity in the cortex and the other 4 patients showed hyperactivity in the basal ganglia. Angiography confirmed spontaneous recanalization of occluded vessels in accordance with the area of hyperactivity. In both patients with cortical hyperactivity, cerebral infarctions were revealed on follow-up CT; in 1 patient, hemorrhagic transformation developed after intraarterial thrombolytic therapy. In 3 of the 4 patients with hyperactivity in the basal ganglia, follow-up CT showed no infarction in the surrounding hypoperfused cortex (selective intraarterial thrombolytic therapy was performed on 2 patients), although various degrees of infarction were observed in the basal ganglia. Obvious infarctions developed in the basal ganglia and the cortex of the other patient. CONCLUSION: Hyperactivity of HMPAO could be seen in the basal ganglia and the cortex within 6 h after onset, reflecting spontaneous recanalization. The areas of hyperactivity may develop infarctions, whereas the accompanying areas of hypoactivity could be rescued by selective intraarterial thrombolytic therapy.

Acute Disease↗
PubMed2001

[A case of pulmonary lymphangioleiomyomatosis originally treated as bronchial asthma].

The subject was a 37-year-old woman in whom bronchial asthma had been diagnosed, for which inhaled steroid and theophylline had been prescribed for about nine months. Her symptoms improved temporarily, but there-after she experienced gradually worsening dyspnea on exertion. Chest radiographs showed diffuse reticulonodular shadows, but no evidence of hyperinflation or pleural effusion. Chest CT scans revealed multiple thinwalled cystic lesions in both lung fields. Pulmonary lymphangioleiomyomatosis was confirmed by thoracoscopic lung biopsy, and medroxyprogesterone was prescribed. Her airways appeared to demonstrate hyperresponsiveness to inhaled methacholine and her symptoms resembled those of bronchial asthma. The relationship between pulmonary lymphangioleiomyomatosis and airway hyperresponsiveness should be considered in future.

Adult↗
PubMed2001

[The practice of the genetical diagnosis and its problems].

Carcinoma is a genetic disease. The malignant phenotype is acquired only after several mutations lead to derangement in a variety of gene products. Traditional methods in molecular biology generally work on a "one gene in one experiment" basis, which means that the throughput is very limited and the "whole picture" of gene function is hard to obtain. In recent years, new technology, called DNA microarray, has attracted interest. This technology promises to monitor the whole genome on a single chip so that researchers can have a better picture of the interactions among thousands of genes simultaneously. In cancers, the detection of minimal residual disease may have prognostic and therapeutic implications. Molecular tools are being used more frequently to enhance the detection of minimal residual disease in many types of cancer. Reverse-transcription polymerase chain reaction (RT-PCR) amplification of genes expressed by the tumor in a tissue-specific manner is the method with the highest diagnostic sensitivity. Quantification of tumor mRNA markers expressed by occult circulating tumor cells may be of prognostic value in a variety of neoplasms and disease stages. Medical professionals need to understand the basic concepts and principles of genetics; the role of genetics in diagnosing and managing different cancers; the ethical, legal and social issues surrounding genetic predisposition testing; and how to manage long-term care of patients at high risk for cancer.

Genes, Tumor Suppressor↗