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Biomedical subjects

S Ohta

Publications and source records attributed to S Ohta.

At least 91 records · Page 5Linked to original sources

Decreased expression of Bcl-x protein during hepatocarcinogenesis induced exogenously and endogenously in rats.

Dysregulations of apoptosis have been widely recognized as important events in multi-stage carcinogenesis. Bcl-x, a member of the Bcl-2 family, is known to act as a regulator of apoptosis. The present study was conducted to assess the role of altered Bcl-x protein expression in exogenous and endogenous hepatocarcinogenesis in rats. In the short-term exogenous models, male Fischer 344 rats, 6 weeks old, were given a single intraperitoneal injection of diethylnitrosamine (DEN) at a dose of 200 mg / kg body weight, partially hepatectomized at the end of week 3, administered phenobarbital at a concentration of 0.05% from the end of week 2 for 6 weeks, and sacrificed. In the livers, glutathione S-transferase (GST-P)-positive, putative preneoplastic lesions were induced, and Bcl-x protein expression was decreased in 24.7% of such lesions. The incidence of GST-P-positive lesions with decreased Bcl-x increased depending on the size of the lesions; 18.9%, 32.4% and 86.5% in the lesions smaller than 0.03, between 0.03 and 0.3, and larger than 0.3 mm(2), respectively. In GST-P-positive lesions larger than 0.3 mm(2), both apoptosis induction and cell proliferation activity were enhanced when Bcl-x protein expression was decreased. In the long-term exogenous models, rats were given 10 mg / kg of DEN, partially hepatectomized 4 h after treatment, administered 0.5 mg / kg of colchicine at the end of days 1 and 3, subjected to a selection procedure, and sacrificed at the end of week 45. Hepatocellular carcinomas were induced with the decreased Bcl-x protein expression. In the endogenous model, rats were fed a choline-deficient, L-amino acid-defined diet for 16 or 80 weeks and sacrificed. Bcl-x protein expression was decreased both in GST-P-positive lesions and hepatocellular carcinoma. These results suggest that this decrease of Bcl-x protein might serve as an indicator of the advanced form of preneoplastic lesions, and that this decrease could also be associated with a potential to progress into carcinoma in both exogenous and endogenous hepatocarcinogenesis of rats.

Alkylating Agents↗

Ibudilast: a non-selective PDE inhibitor with multiple actions on blood cells and the vascular wall.

Ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine) is a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It is widely used in Japan for improving prognosis and relieving symptoms in patients suffering from ischemic stroke or bronchial asthma. These clinical applications are based on the properties of ibudilast that inhibit platelet aggregation, improve cerebral blood flow and attenuate allergic reactions. The inhibition of platelet aggregation and vasodilatation by ibudilast may be due to synergistic elevation of intracellular cyclic nucleotides and release of nitric oxide (NO) or prostacyclin from endothelium, rather than direct inhibition of PDE5 or PDE3. Another important property of ibudilast is its antiinflammatory activity possibly associated with potent inhibition of PDE4. Combined with its relaxing effects on bronchial smooth muscle, antiinflammatory activity of ibudilast could favorably influence pathophysiology of asthma by antagonizing chemical mediators triggering asthmatic attacks. Ibudilast was also reported to significantly attenuate inflammatory cell infiltration in the lumbar spinal cord in an animal model of encephalomyelitis. Future investigations should include effects of ibudilast on inflammatory reactions between endothelium and blood cells, which may initiate the development of atherosclerosis.

Animals↗

Genome relationships in the genus Dasypyrum (Gramineae).

To elucidate the genome relationships in the genus Dasypyrum and the ancestry of tetraploid D. breviaristatum, two cytotypes of D. breviaristatum and D. villosum were reciprocally crossed with one another. Chromosome pairing at the first metaphase of meiosis and fertility were examined in the F1 hybrids and the parental plants. The mean pairing configuration and mean arm pairing frequency in D. villosum-D. breviaristatum (2x) hybrids were 11.12I + 1.44II per cell and 0.107, respectively, and they were almost completely sterile. In D. breviaristatum (4x)-D. breviaristatum (2x) hybrid, up to seven trivalents were formed, and the mean pairing configuration was 3.38I + 3.20II + 3.74III + 0.005IV per cell. The mean arm pairing frequency and relative affinity calculated in that F1 hybrid were 0.915 and 0.641, respectively. Seven bivalents and seven univalents were characteristically formed in D. villosum-D. breviaristatum (4x) hybrids. Based on the present results, we clearly concluded that the genome of diploid D. breviaristatum is distantly related to the genome V of D. villosum, and that these two species have different basic genomes. We, therefore, proposed the symbol Vb for the haploid genome of diploid cytotype of D. breviaristatum. Moreover, we concluded that tetraploid D. breviaristatum is an autotetraploid with doubled sets of the genomes homologous with that of diploid D. breviaristatum, and we proposed the genome constitution VbVb for the haploid genome set of tetraploid cytotype of D. breviaristatum. Furthermore, from the chromosome pairing in the F1 hybrids involving Moroccan and Greek accessions, it was suggested that complicated rearrangements of chromosome structure have occurred in tetraploid D. breviaristatum in its natural populations across the entire distribution area.

Chromosomes↗

Increased proportion of HLA-class-I-specific natural killer cell receptors (CD94) on peripheral blood mononuclear cells after allogeneic bone marrow transplantation.

In the present study, we investigated the inhibitory natural killer cell receptor (NKR) expression of CD94/NKG2A on PBMC after allogeneic bone marrow transplantation (BMT). The proportion of CD94 expression on PBMC was higher in patients without chronic graft-versus-host disease (cGVHD) and also in cGVHD patients with good response to conventional immunosuppressive therapy than in cGVHD patients with poor response. Also, the proportions of CD94+/CD3+ cells and CD94+/CD8+ cells were higher in cGVHD patients showing good response. In addition, the proportion of NKG2A-expressing cells was higher in patients without cGVHD than in patients with cGVHD. Therefore, chronic allostimulation after allo-BMT may augment the proportion of CD94/NKG2A-positive cells, and these cells may play some role in the regulation of alloresponse in some patients.

Antigens, CD↗

The optimal stimulation site for chronic stimulation of the subthalamic nucleus in Parkinson's disease.

To determine the optimal stimulation site within the subthalamic nucleus (STN), monopolar stimulation of four electrode contacts and the resulting effects on parkinsonian symptoms were evaluated in 10 consecutive patients. The UPDRS score for rigidity and akinesia improved significantly after stimulation at each of the contacts, compared to the pre-evaluation state (Fisher's test, p < 0.05). The most significant improvement was obtained after stimulation at contact-2 (rigidity: 74.4 +/- 20.4%, akinesia: 53.7 +/- 14.3%) (Fisher's test, p < 0.001). Contact-2 was located at the dorsal border of the STN at a mean distance of 0.3 +/- 0.7 mm. DBS at the dorsal border of the STN, where the stimulation affects the neurons as well as their axonal fibers, produces the greatest clinical improvement in parkinsonian symptoms.

Brain Mapping↗

A comparative study of characteristics of current-type and conventional-type cationic bactericides.

We have synthesized new polycationic bactericides, polyloxyethylene(dimethyliminio)trimethylene(dimethyliminio)ethylene dichloridel (OXD) and poly(hexamethyleneguanidine phosphate) (HEP), in order to develop more active but less skin-irritative bactericides. The effects of these bactericides on Pseudomonas aeruginosa, Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, methicillin resistant Staphylococcus aureus (MRSA) and the degree of their irritations on skin were compared with those of a widely used low molecular-weight cationic bactericide, benzalkonium chloride (BAC), and a polycationic bactericide, poly[2-hydroxyethylene(dimethyliminio)methylene chloride] (2HYC). The minimum bactericidal concentration (MBC) of OXD for 10 min contact incubation was 16 microg/ml against P. aeruginosa, E. coli, S. marcescens and K. pneumoniae, and >1000 microg/ml against MRSA. The MBC of HEP for 10 min contact incubation was 16 microg/ml against P. aeruginosa, 32 microg/ml against E. coli and K. pneumoniae, and 64 microg/ml against S. marcescens and MRSA. Itch, edema, erythema, heat, injury, desquamation and keratinization caused by skin irritation were examined in 21 subjects by patch tests. Only one subject treated with OXD experienced edema, and one subject with HEP experienced keratinization. However, BAC caused itch in 3 subjects, edema in 1, erythema in 10 and desquamation in 2, indicating that the incidence of skin irritation of BAC was higher than that of OXD or HEP. OXD and HEP had sterilization ability similar to BAC, however, they were less skin-irritative than BAC. This indicates that OXD and HEP can be used as safe bactericides.

Adult↗

Extremely high drug-reductase activity based on aldehyde oxidase in monkey liver.

Drug-reducing ability of monkey liver cytosol was examined in this study. Monkey liver cytosol exhibited significant reductase activities toward zonisamide, sulindac and imipramine N-oxide in the presence of 2-hydroxypyrimidine or benzaldehyde, an electron donor to aldehyde oxidase. These activities were abolished by inhibitors of aldehyde oxidase, such as menadione. These reductase activities in monkeys were extremely high compared to those in other animals. The zonisamide reductase activity of monkey liver cytosol was about 40-fold higher than that of the liver microsomes. It appears that the high levels of aldehyde oxidase exists in monkey liver, and zonisamide, sulindac and imipramine N-oxide are mainly reduced by this enzyme, not by cytochrome P450.

Aldehyde Oxidase↗

Variation and geographical distribution of the genotypes controlling the diagnostic spike morphology of two varieties of Aegilops caudata l.

Aegilops caudata L. is an annual wild relative of wheat distributed over the northeastern Mediterranean basin. It consists of two taxonomic varieties, var. typica with awnless lateral spikelets and var.polyathera with awned lateral spikelets. To clarify the variation and the geographical distribution of the genotypes controlling the diagnostic spike morphology of the two taxonomic varieties, three crossing experiments were carried out. First, two varieties collected from nine sympatric populations in the Aegean islands were crossed reciprocally. All of the F1 hybrids were var. typica and the segregation ratio in the F2 generation was 3 typica: 1 polyathera. Secondly, 13 typica accessions collected from the entire distribution area of the variety were crossed with a common polyathera accession. The F1 hybrids involving eight typica accessions from Greece and West Anatolia were var. typica, while those involving five typica accessions from East Anatolia, Syria and Iraq were var. polyathera. Thirdly, the typica F1 hybrids between the Aegean and the Syrian typica accessions were backcrossed to the latter. Four of the seven BC1F1 plants obtained were var. typica, but the other three were var. polyathera. Based on these results, the following two conclusions were made. First, the awnless lateral spikelets characteristic of var. typica are due to two different genotypes: one is a dominant allele suppressing awn development on lateral spikelets and the other is a recessive allele(s) for awnless lateral spikelets with no dominant suppressor allele. Secondly, the former genotype occurs only in the western region of the distribution area of the species, while the latter occurs in the eastern region. The present results and the recent palaeopalynological evidence also suggested that var. polyathera, with more awns than var. typica, rapidly colonized Central Anatolia from the Levant or East Taurus/Zagros mountains arc after the last glacial period.

Crosses, Genetic↗

Phylogeny of hydrothermal-vent-endemic gastropods Alviniconcha spp. from the western Pacific revealed by mitochondrial DNA sequences.

Mitochondrial genes for cytochrome oxidase I (COI) from hydrothermal-vent-endemic gastropods of the genus Alviniconcha were sequenced to determine the phylogenetic relationships among specimens from three areas in the western Pacific. Individuals of Alviniconcha hessleri were collected at two vent fields (depths 1470 m and 3600 m) in the Mariana Trough. Specimens collected in the North Fiji Basin could be divided into two genetically distinct groups, both of which also differed from A. hessleri from the Mariana Trough. None of the specimens of the genus Alviniconcha collected in the Manus Basin differed genetically from the dominant group from the North Fiji Basin. We suggest that the specimens of the genus Alviniconcha analyzed in the present study can be tentatively classified into A. hessleri and two undescribed species.

Animals↗

Dimethyl sulfoxide inhibits dimethylnitrosamine-induced hepatic fibrosis in rats.

We studied the preventive effects of dimethyl sulfoxide (DMSO) on experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN caused a significant decrease in body and liver weight. Oral DMSO (2 ml/kg daily for 4 weeks) essentially prevented this DMN-induced body and liver weight loss with no major side effects. DMSO suppressed the induction of hepatic fibrosis, as determined by histological evaluation, and reduced hepatic hydroxyproline. It also suppressed the expression of mRNA for type I collagen in the liver. Because hepatic stellate cells (HSC) are the major cellular source of the collagen in hepatic fibrosis, we examined the effects of DMSO on collagen production in vitro using rat primary HSC culture. However, it was found that DMSO did not inhibit the collagen production in vitro. We next evaluated the effects of DMSO on tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO) production by Kupffer cells, because these factors represent major activator of HSC, and because monocyte-macrophage infiltration has been implicated as being pathogenetically important for hepatic fibrosis induced by DMN. DMSO inhibited lipopolysaccharide (LPS)-induced TNFalpha and NO production, and reduced TNFalpha mRNA levels. DMSO also suppressed the LPS-induced nuclear factor kappa B activation in a murine macrophage-like cell line. These results suggest that the inhibitory effects of DMSO on hepatic fibrosis may be primarily exerted via blocking of DMN-induced inflammation. These results also implied that DMSO may be potentially useful for preventing the development of hepatic fibrosis.

Animals↗

[Childhood t(8;21) acute myelocytic leukemia: a comparison of clinical features and risk factors with adult cases].

Despite the abundance of reports describing adult cases of t(8;21) acute myelocytic leukemia (AML), childhood cases have received little attention. We retrospectively investigated 14 childhood cases of t(8;21) AML, and compared their clinical characteristics with those of adult cases, focusing on the risk factors for poor prognosis. Seventy-one percent of the patients had fever. Their mean leukocyte count was 12,700/microliter, and they showed decreased NAP activity. The cell surface showed positivity for CD13, 33, 19, 34, and HLA-DR. The complete remission rate was 100%, and relapse was observed in three of the patients. Bone marrow eosinophilia was present in a smaller proportion of the childhood cases than in the adult cases. Although an increased leukocyte count, tumor formation, and other risk factors have been reported in adults, there was no correlation between these factors and prognosis in our childhood cases. As children who showed AML relapse had TdT-positive blasts, detectable blast TdT activity may be a risk factor for relapse in childhood cases of t(8;21) AML. However, to confirm this, a study with a larger subject base should be conducted.

Adolescent↗

[A-56-year-old woman with parkinsonism, whose mother had Parkinson's disease].

We report a 56-year-old woman with progressive gait disturbance. Her mother had Parkinson's disease with onset at age 70. She died at age 74 and the post-mortem examination confirmed the diagnosis of Lewy body positive Parkinson's disease. The patient was well until the age of 50(1995) when she noted an onset of resting tremor and difficulty of gait. She also developed delusional ideation and was admitted to a psychiatric service of another hospital, where a major tranquilizer was given. The delusion disappeared but she developed marked rigidity. The major tranquilizer was discontinued and an anticholinergic and amantadine HCl were given. She showed marked improvement to Hoehn and Yahr stage II and was discharged. In 1995, when she was 52 years of the age, she developed delusion again and a major tranquilizer was given. She developed marked parkinsonism again and became Hoehn and Yahr stage V. The major tranquilizer was discontinued and she was treated with levodopa/carbidopa, trihexyphenidyl, bromocriptine, and dops. She improved remarkably to stage II. She was admitted to our service on October 8, 1996 for drug adjustment. She was alert and not demented. She was anxious but delusion or hallucination was noted. Higher cerebral functions were intact. Cranial nerve functions were also intact except for masked face and small voice. Her posture was stooped and steps were small. She showed retropulsion and moderate bradykinesia. Resting tremor was noted in her left hand. Rigidity was noted in both legs. No cerebellar ataxia or weakness was noted. Deep tendon reflexes were within normal range and sensation was intact. Her cranial MRI revealed some atrophic changes in the putamen, in which a T 2-high signal linear lesion was seen along the lateral border of the putamen bilaterally. In addition, posterior part of the putamen showed T 2-low signal intensity change. She was treated with 1.6 mg of talipexole, 6 mg of trihexyphenidyl, and 100 mg of L-dops. She was in stage III of Hoehn and Yahr. She developed neurogenic bladder with a large amount of residual urine for which she required catheterization. She was transferred to another hospital. Despite drug adjustment, she lost response to levodopa and her parkinsonism deteriorated gradually. She also developed syncope orthostatic hypotension. In April of 1998, she developed intracerebral hemorrhage and was admitted again on April 19, 1998. She was unable to stand and showed marked akinesia and rigidity. She was in stage V of Hoehn and Yahr. Her cranial CT scan revealed bilateral high-density lesions in the posterior parietal lobes. She developed dysphagia for which she required gastrostomy. She was transferred to another hospital but her clinical condition deteriorated further. On December 22, 1999, she developed fever and dyspnea and was admitted to our service again. She developed cardial arrest at the emergency room from hypoxia. She was resuscitated; however, she was comatose with loss of brain stem reflexes. Later on she developed generalized myoclonus. She developed cardiac arrest and pronounced dead on December 28, 1999. The patient was discussed in a neurological CPC. The chief discussant arrived at the conclusion that the patient had striatonigral degeneration because of poor response to levodopa in the later course, autonomic failures, and MRI changes. Some other participants thought that the patient had a form of familial Parkinson's disease. Opinions were divided into these two possibilities. Post-mortem examination revealed that the substantia nigra showed intense neuronal loss and gliosis, however, no Lewy bodies were seen. In addition, intracytoplasmic inclusions were seen in oligodendrocytes. The putamen was markedly atrophic in its posterior part with marked gliosis and neuronal loss. The ventromedial part of the pontine nucleus also showed neuronal loss and intracytoplasmic glial inclusions. Pathologic diagnosis was multiple system atrophy. In the parietal lobe, an arteriovenous malformation with bleeding was noted. This is very unique case. Although her mother had Lewy body-positive Parkinson's disease, the patient had Lewy body-negative multiple system atrophy with a-synuclein-positive glial inclusions. Whether this is just a coincidental occurrence or the presence of a genetic load for Parkinson's disease might triggered her multiple system atrophy is an interesting question to be answered in future.

Brain↗

[Fatal stenosis of trachea and main bronchus due to compression by the spine and sternum in three patients with severe motor and intellectual disabilities].

Three patients with severe motor and intellectual disabilities developed fatal respiratory insufficiencies caused by stenosis of the trachea and main bronchus due to compression by the spine and trachea. The onset of respiratory insufficiency was by 20, 16, and 29 years of age. Chest computed tomography demonstrated deformation and narrowing of the trachea and main bronchus, and shortening of the distance between spine and sternum. Although respiratory insufficiency was temporarily relieved by insertion of a stent into the main bronchus in patient 1, he died at the age of 21 due to proliferation of granulation tissue. Patient 2 died of bleeding from the granulation tissue around the window of tracheotomy at the age of 18 years, and patient 3 died of recurrent pneumonia at the age of 34 years. In conclusion, stenosis of the trachea and bronchus observed in these patients was caused by progressive deformation of the thorax. The stenosis may result in sudden death or recurrent respiratory infections in patients with severe motor and intellectual disabilities.

Adolescent↗

Tumor necrosis factor-alpha (TNF-alpha) converting enzyme contributes to production of TNF-alpha in synovial tissues from patients with rheumatoid arthritis.

OBJECTIVE: Expression and function of tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) in synovia of patients with rheumatoid arthritis (RA) were examined to investigate posttranslational regulation of TNF-alpha production by TACE in RA. METHODS: Expression of TACE protein was evaluated by immunohistochemistry. Cytokines and soluble cytokine receptors were measured by ELISA. TACE mRNA was detected by RT-PCR. The enzymatic activity of TACE was measured using TACE-specific fluorogenic substrate. RESULTS: Expression of TACE at protein level in synovial tissue (ST) of patients with RA was significantly stronger than that of patients with osteoarthritis (OA). In RA, TACE was mainly expressed in CD68+ macrophage-like synovial cells. ST from 9 of 9 RA and 3 of 8 OA patients expressed TACE mRNA. RA ST cells possessed significantly higher TACE-like enzymatic activity than OA ST. A synthetic TACE inhibitor significantly reduced the release of TNF-alpha and p75 TNF receptor from RA ST cells. CONCLUSION: TACE is an important regulator of the secretion of TNF-alpha from synovia of patients with RA.

ADAM Proteins↗

Mature form of interleukin 18 is expressed in rheumatoid arthritis synovial tissue and contributes to interferon-gamma production by synovial T cells.

OBJECTIVE: To investigate the expression and function of interleukin 18 (IL-18) in synovial tissue (ST) of patients with rheumatoid arthritis (RA). METHODS: The localization of IL-18 in ST was analyzed by immunohistochemistry. IL-18 and IL-18 receptor (IL-18R) mRNA were detected by RT-PCR. Expression of IL-18 at the protein level was analyzed by Western blotting. Cytokines in culture supernatants were measured by ELISA. RESULTS: From immunohistochemical analysis, IL-18-producing cells were localized in the lining layer and sublining region of RA ST. Most of them coexpressed CD68 antigen. In ST from patients with osteoarthritis (OA), IL-18-producing cells were localized only in the sublining region and the numbers of these cells were small. From RT-PCR, RA ST expressed mRNA of IL-18, as well as alpha- and beta-chains of IL-18R. OA ST did not express or very weakly expressed mRNA of alpha- and beta-chains of IL-18R. ST from RA patients produced significantly larger amounts of IL-18 in vitro than OA ST. Western blotting revealed that RA ST expressed mature IL-18 more abundantly than OA ST. IL-12 alone stimulates interferon-gamma (IFN-gamma) production by RA synovial tissue cells, but IL-18 alone could not. In the presence of IL-12, however, IL-18 could synergistically stimulate IFN-gamma production by RA synovial tissue cells. OA synovial tissue cells responded to neither IL-12 nor IL-12 + IL-18. IL-18 showed synergistic effects with IL-12 on promoting the ability of synovial T cells from RA patients to produce IFN-gamma. CONCLUSION: These findings suggest that mature IL-18 is expressed in RA synovia and contributes to the production of IFN-gamma by infiltrating T cells.

Arthritis, Rheumatoid↗