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Biomedical subjects

H Ono

Publications and source records attributed to H Ono.

At least 217 records · Page 12Linked to original sources

Comparative effects of disulfiram and diethyldithiocarbamate against testicular toxicity in rats caused by acute exposure to cadmium.

Disulfiram (DSF) and diethyldithiocarbamate (DED) were compared for their protective effects against the testicular toxicity induced by acute exposure to cadmium (Cd) in rats. Rats were injected subcutaneously with CdCl2 126.7 mumol (3 mg) Cd/kgl, and 30 min later they were injected intraperitoneally with DSF (0.05-0.5 mmol/kg) or DED (0.1-1 mmol/kg). The treatment with DSF at dose levels of 0.1-0.5 mmol/kg prevented the increases in testicular lipid peroxidation and calcium (Ca) concentrations and the decreases in testicular weight that were observed at 7 d after Cd injection. DED at dosage levels of 0.2-1 mmol/kg likewise reduced Cd-induced testicular toxicity. An increase in testicular iron (Fe) concentrations at 7 d and sterility at 59 d after Cd injection were almost completely blocked by treatment with DSF or DED at the highest doses, but lower doses of DSF or DED were ineffective. These results indicated that DSF, which is metabolized to DED, had a protective effect against Cd-induced testicular toxicity nearly equivalent to DED at approximately one-half the dose.

Animals↗

Clinicopathological studies on coexisting gastric malignant lymphoma and gastric adenocarcinoma: report of four cases and review of the Japanese literature.

Among 121 cases of primary gastric malignant lymphoma from 1962 to 1994 at the National Cancer Center Hospital, Tokyo, we found four cases (three males and one female) of adenocarcinoma coexisting in the stomach. The incidence of gastric malignant lymphoma together with gastric adenocarcinoma was 3.3%, suggesting that patients with lymphoma may have an increased incidence of gastric adenocarcinoma. A review of the Japanese literature revealed an additional 62 patients who developed coexisting gastric malignant lymphoma and adenocarcinoma. In the total series of 66 patients whose age and sex were recorded, there were 48 males with a mean age of 63.8 years and 18 females with a mean age of 58.6 years. Most adenocarcinomas were macroscopically early (76%) and of histologically differentiated type (75%). Conversely, 71% of lymphomas were of the advanced type macroscopically. The correct preoperative diagnoses were made in only 27% (16/59) of cases, when both tumors were located independently.

Adenocarcinoma↗

Vascularized fibular graft for reconstruction of the wrist after excision of giant cell tumor.

Seven patients with a giant-cell tumor involving the distal end of the radius were treated with en bloc resection and reconstruction with a free vascularized fibular graft. Two patients with stage 2 disease of Enneking's surgical staging and grade 2 of Campanacci's radiographic grading system were reconstructed with an articular fibular head graft. Five patients with stage 3 and grade 3 disease underwent wrist arthrodesis using fibular shaft transfer. There was radiographic evidence of bone union at the host-graft junctions in all cases. No local recurrence was seen in any of the patients at the most recent follow-up examinations. There were six good and one excellent functional results. Wrist arthroplasty using a vascularized fibula head graft is the best procedure for a stage 2 or grade 2 giant-cell tumor of the distal end of the radius. In cases of stage 3 or grade 3 disease, wrist arthrodesis using a vascularized fibular shaft graft is indicated.

Adolescent↗

Expression of Bcl-2 in human breast cancer: correlation between hormone receptor status, p53 protein accumulation and DNA strand breaks associated with apoptosis.

The expression of Bcl-2, a suppressor of apoptotic cell death, was investigated in 52 invasive carcinomas of the breast using reverse transcription-polymerase chain reaction and immunohistochemical methods. After consideration of both sets of results, 42 tumors (80.8%) were confirmed to be positive (Bcl-2(+)) and 10 (19.2%) were judged negative (Bcl-2(-)) for Bcl-2 expression. Related factors (p53 protein accumulation, hormone receptor status and apoptotic cell index) were also examined using immunohistochemical and in situ end-labeling methods to elucidate their correlations with Bcl-2 expression. Bcl-2 expression correlated significantly with the hormone receptor status, whereas it showed significant inverse correlations with p53 accumulation and the apoptotic index. It was concluded that estrogen and mutant p53 are related to the regulation of Bcl-2 expression and that the ability to prevent tumor cell death due to Bcl-2 can be developed by breast cancers.

Apoptosis↗

Transgenic medaka fish bearing the mouse tyrosinase gene: expression and transmission of the transgene following electroporation of the orange-colored variant.

Transgenic fish bearing the mouse tyrosinase gene (mg-Tyrs-J) were produced by transfection into fertilized eggs of the homozygous normal orange-colored variant of medaka fish, Oryzias latipes, by means of electroporation. Of 589 eggs transfected, 38 fish (6%) exhibited brownish wild-type skin pigmentation, which was discernible from control siblings. Light microscopy of the skin from the founders thus generated disclosed that 1) melanization occurred and was restricted to melanophores formed presumably from pre-existing amelanotic melanophores, 2) there was a wide variation in the degree of melanization observed among melanophores, and 3) no melanin deposition was recognized in xanthophores or leucophores. Immunofluorescence using an antibody raised against mouse tyrosinase disclosed that melanophores at varying stages of maturation were reactive. Thus, it was shown that the transgene in medaka fish expressed its action in a cell type-specific manner. Crossing of transgenic founders with homozygous orange-colored variant fish yielded two groups of offspring expressing either the wild-type or the orange-colored skin pigmentation at an approximate ratio of 1:1. Crossing between founders exhibiting wild-type pigmentation yielded only offspring with melanized skin. Skin melanophores in these offspring formed vertical stripes, which are rare in this species. The hereditary basis of melanized skin was demonstrated in matings of F1 progenies, which resulted in similar degrees of melanization over whole skin melanophores. The sum of these findings implied that the transgene is expressed as a dominant character gene and is transmitted through germ cell lines according to the Mendelian law. PCR analysis combined with nested PCR technique strongly suggested that the transgene was integrated into the medaka genome, even though the copy number deduced from gel banding was largely diminished, possibly as a result of fragmentation or instability within the medaka genome.

Animals↗

Granuloma annulare in a patient with malignant lymphoma.

We describe the case of a 69-year-old man with malignant lymphoma who developed granuloma annulare on his fingers. The number of cutaneous nodules increased when a recurrence of lymphoma was demonstrated during the course of disease. Granulomatous lesions disappeared after the fifth cycle of chemotherapy with CHOP (cyclophosphamide, Adriamycin, vincristine, prednisolone). The coexistence of these two diseases is relatively rare. The clinical features seen in this case, however, might suggest that granuloma annulare is a generalized granulomatous reaction induced by malignant lymphoma.

Aged↗

Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer.

PURPOSE: A dose-escalation study of irinotecan hydrochloride (CPT-11) combined with fixed-dose cisplatin was conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and objective response rate in patients with advanced gastric cancer. PATIENTS AND METHODS: Twenty-four patients with or without prior chemotherapy were enrolled. All patients were assessable for toxicities and response. On day 1, CPT-11 was administered as a 90-minute intravenous (I.V.) infusion, which was followed 2 hours later by a 120-minute I.V. infusion of cisplatin 80 mg/m2. CPT-11 alone at the same dose was administered again on day 15. The treatment was repeated every 4 weeks until disease progression was observed. The initial dose of CPT-11 was 60 mg/m2, and was escalated in increments of 10 mg/m2 until severe or life-threatening toxicity was observed. RESULTS: The MTD of this combination was CPT-11 80 mg/m2. At this dose level, 16.7% of patients (two of 12) had leukopenia of less than 1,000/microL, 66.7% (eight of 12) had neutropenia of less than 500/microL, and 16.7% (two of 12) had severe diarrhea of grade 4 during the first course. The dose-limiting toxicity was neutropenia. Ten patients achieved a partial response (PR), and the overall response rate was 41.7% among 24 patients (95% confidence interval, 21.9% to 61.4%). CONCLUSION: The recommended dose and schedule is CPT-11 70 mg/m2 on days 1 and 15 and cisplatin 80 mg/m2 on day 1 every 4 weeks. This combination of CPT-11 and cisplatin, considered to be active against advanced gastric cancer with acceptable toxicity, should be further assessed in a phase II study.

Adult↗

Relationship between duration of rheumatoid arthritis before knee joint surgery and HLA-DRB1 alleles: a retrospective study.

OBJECTIVE: To examine whether genetically determined factors can be used as predictors of requirement for knee joint surgery in the early phase of rheumatoid arthritis (RA). METHODS: We determined HLA-DRB1 alleles in 322 patients with seropositive RA by polymerase chain reaction and allele specific oligonucleotide probe techniques. Patients were classified into 3 groups (S/S, S/N, and N/N) based on their possession of two, one or no susceptibility alleles of RA, respectively. The stage of radiographic change in the knee joint determined using Larsen's standard film was compared to results of genotyping. Duration of RA before joint surgery in the 3 groups was also compared retrospectively. RESULTS: The median number of years to develop to stages I, II, III, and IV and the number of years of disease duration before total knee arthroplasty (TKA) were significantly shorter in the S/S group than in the S/N and N/N groups (p < 0.05). CONCLUSION: TKA was required earlier in the S/S group than in the S/N and N/N groups. This finding will affect planning of surgical management for RA based on anticipated courses.

Adult↗

Histologic features and clinical significance of venous invasion in colorectal carcinoma with hepatic metastasis.

BACKGROUND: In colorectal carcinoma, venous invasion has been related to patient survival. Liver metastasis develops more frequently when venous invasion is present. However, the histologic features and clinical significance of venous invasion are not well understood. METHODS: A histologic study of venous invasion in colorectal carcinoma was performed on 19 patients with synchronous hepatic metastasis (Group A), 16 patients with metacaronous hepatic metastasis (Group B), and 26 patients with Dukes Stage C tumors who survived for 5 years without recurrence (Group C). The histologic features of venous invasion were classified into three types: tumor cells that were distant from the vein walls were categorized as floating type, those filling the lumen of a vein as filling type, and those surrounded by a vein obliterated with inflammatory reaction as occlusive type. RESULTS: Venous invasion was present in 89.5% of Group A patients and 75% of Group B patients, which was significantly higher than the 15.4% observed in Group C patients (P < 0.001). A slight to extensive degree of venous invasion was found in Groups A and B, but no extensive venous invasion was found in Group C. All patients in Groups A and B (except one patient) had floating, filling, or a combination of floating and filling types of venous invasion, whereas all patients in Group C had the occlusive type of venous invasion. A majority of the patients in all three groups showed invasion of extramural veins. CONCLUSIONS: There is a close relationship between venous invasion and the development of liver metastasis in patients with colorectal carcinoma. Patients with no sign of metastasis had a lower incidence and lower extent of venous invasion, and inflammatory damage to the vein walls around the intravenous tumor appeared to reduce the likelihood of distant metastasis.

Adult↗

Effects of 8-OH-DPAT, a 5-HT1A receptor agonist, and DOI, a 5-HT2A/2C agonist, on monosynaptic transmission in spinalized rats.

We investigated the effect of 5-HT1A receptor agonist (-/+)-8-hydroxy-2-(di-N-propylamino)tetraline (8-OH-DPAT) and the 5-HT2A/2C receptor agonist (-/+)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on monosynaptic transmission in spinalized rats. 8-OH-DPAT significantly inhibited the excitation of alpha-motoneurons evoked by monosynaptic transmission without a direct effect on alpha-motoneuron excitation. DOI potentiated the excitation of alpha-motoneurons by both direct stimulation and monosynaptic transmission. These results indicate that activation of 5-HT1A receptors inhibits monosynaptic transmission, whereas activation of 5-HT2A/2C receptors enhances it.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Characterization of alpha 1-adrenoceptor subtypes in rat spinal cord.

The alpha 1-adrenoceptor subtypes in ventral and dorsal horns of rat lumbar spinal cord were studied. High concentrations of the alpha 1D-adrenoceptor antagonist, BMY 7378 (8-[2-[4-(2-methoxyphenyl) 1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride), displaced bound [3H]prazosin in a single-site manner and the binding affinity was close to those for alpha 1A- and alpha 1B-adrenoceptor binding sites. 5-Methyl-urapidil displaced bound [3H]prazosin in a two site manner and the high and low affinities were close to those of alpha 1A- and alpha 1B-adrenoceptor binding sites, respectively. The alpha 1-adrenoceptor subtype populations of ventral and dorsal horns did not differ. The alpha 1A- and alpha 1B-adrenoceptor populations comprised 70% and 30%, respectively, of the total and very few alpha 1D-adrenoceptors were detected.

Animals↗

Peroxidase-catalyzed generation of catechin oligomers that inhibit glucosyltransferase from Streptococcus sobrinus.

Oolong tea extract (OTE) and the purified polymeric polyphenols from OTE have been found to inhibit glucosyltransferase (GTase) of mutans streptococci. In view of the partial fermentation characteristic of oolong tea, we describe here an in vitro model reaction system to produce partially fermented products of D-(+)-catechin or green tea extract (GTE) using horseradish peroxidase. A dimeric catechin molecule was identified as dehydro-dicatechin A by instrumental analyses. The molecular size of some oligomeric catechins was estimated by the elution profile with HPLC. These catechin oligomers markedly inhibited GTase from Streptococcus sobrinus 6715. As the degree of polymerization of catechin or GTE increased, GTase was inhibited more effectively. These results suggest that polymeric polyphenols found in OTE are synthesized by partial fermentation due to oxidases/peroxidases present in tea leaves.

Bacterial Adhesion↗

Cyclobenzaprine, a centrally acting muscle relaxant, acts on descending serotonergic systems.

The centrally acting muscle relaxant cyclobenzaprine was thought to be an alpha 2-adrenoceptor agonist that reduced muscle tone by decreasing the activity of descending noradrenergic neurons. In the present study, we examined the effects of cyclobenzaprine on descending neurons by measuring the monosynaptic reflex in rats. Cyclobenzaprine reduced the monosynaptic reflex amplitude dose dependently and this effect was not inhibited by the alpha 2-adrenoceptor antagonists idazoxan and yohimbine. Cyclobenzaprine-induced monosynaptic reflex depression was not attenuated by noradrenergic neuronal lesions produced by 6-hydroxydopamine. However, cyclobenzaprine inhibited monosynaptic reflex facilitation induced by (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane, a 5-HT2 receptor agonist, in spinalized rats markedly, and 5-HT depletion by DL-p-chlorophenylalanine inhibited the depressive effect of cyclobenzaprine on the monosynaptic reflex. These results suggest that cyclobenzaprine is a 5-HT2 receptor antagonist and that its muscle relaxant effect is due to inhibition of serotonergic, not noradrenergic, descending systems in the spinal cord.

Adrenergic alpha-2 Receptor Antagonists↗

Tyrosine kinase inhibitor herbimycin A reduces the stability of cyclin-dependent kinase Cdk6 protein in T-cells.

The Cdk6 protein level rapidly decreased after treatment with the tyrosine kinase inhibitor herbimycin A in human T-cell lines. This decrease is fairly specific, because the level of other Cdks such as Cdk2 and Cdk4 and cyclins such as cyclin D2, cyclin E and cyclin A, did not change significantly even after 24 h treatment with herbimycin A. Pulse-chase analysis revealed that the decrease in the Cdk6 protein level results from reduced stability of the protein. Our results suggest that herbimycin A-sensitive protein tyrosine kinase(s) are involved in the regulation of the Cdk6 protein level.

Animals↗