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H Okuno

Publications and source records attributed to H Okuno.

At least 91 records · Page 5Linked to original sources
PubMed1994

[Assessment of treatment outcome and prognostic factors of renal cell cancer].

We assessed the treatment outcome of 71 patients (45 men and 26 women) with renal cell cancer treated at the Public Toyooka Hospital from 1969 to 1992. The patient's age varied from 15 to 85 (mean 64). The overall actuarial and disease specific survival rates at 5 years were 55% and 67%, respectively. Statistical analysis of various parameters associated with prognosis was performed. The parameters achieving statistical significance were pT, PV, distant metastasis, grade, histological architecture, cell type, tumor size and erythrocyte sedimentation rate.

Adolescent↗
PubMed1993

Configurational encoding of complex visual forms by single neurons of monkey temporal cortex.

Single neurons in the anterior inferior temporal (IT) cortex respond to complex visual stimuli. Here we examined whether the stimulus-selectivity of the anterior IT neurons was determined solely on the basis of the geometric similarity of object forms, or was modifiable through visual experiences in adulthood. We trained Japanese monkeys (Macaca fuscata) in the visual delayed matching-to-sample task or visual stimulus-stimulus association task. Computer-generated visual forms, fractal patterns or Fourier descriptors, were used as stimuli. Single-unit recording from these trained monkeys showed that the stimulus-selectivity of neurons in the anterior IT cortex could be acquired according to the requirements of memory tasks. The results indicate that the neural representation of complex visual objects is dynamically altered through both tuning and association processes. We discuss these neurophysiological findings in relation to neuropsychological investigations of ablation effects in the primate.

Animals↗
PubMed1993

[Vanishing tumor thrombus in IVC after oral administration of UFT and TAE in a patient with HCC; a case report].

A 74-year-old man was diagnosed as hepatocellular carcinoma (HCC) in the area of S6-7 with tumor thrombus continuously developed from hepatic vein to inferior vena cava (IVC). AFP value remained high despite two transcatheter arterial embolizations with adriamycin, mitomycin and Lipiodol (Lp-TAE). The AFP value gradually decreased two weeks after oral administration of UFT. Nine months after, the AFP level was 26.4 ng/ml and the tumor thrombus in the IVC disappeared. The size of the main tumor did not change. This case suggests Lp-TAE and UFT are useful for suppressing the growth of the main tumor and to extinguish the tumor thrombus.

Aged↗
PubMed1993

[Treatment results of total cystectomy for patients with bladder cancer].

We assessed the treatment outcome of total cystectomy for 93 patients (71 men and 22 women) with bladder cancer treated in the Public Toyooka Hospital from 1970 to 1989. Patient age varied from 36 to 87 (mean 67). The overall actuarial survival rates at 5 and 10 years were 51% and 36%, respectively. The 5-year survival rates were 72% for grade 2 and 44% for grade 3 disease. The 5-year survival rates according to the pathological stage were 66% for pT0-1, 51% for pT2, 35% for pT3, 44% for pT4a disease. A statistical difference was noted between the 5-year survival rate of patients with pT0-2 disease and that with pT3. Patients with pT4aN0 disease showed a relatively high survival rate (67%). The 5-year survival rates were 54% for the patients with negative lymph node and 22% for those with positive lymph node. Although we could not demonstrate the efficacy of preoperative radiotherapy, the combination of radiation and chemotherapy was suggested to improve the survival after cystectomy. Patients who received simultaneous urethrectomy showed a higher 5-year survival rate as compared to those who did not.

Adult↗
PubMed1993

Depression of drug-metabolizing activity in the human liver by interferon-beta.

The depressant effect of interferon beta on drug-metabolizing activity in the human liver was investigated. Seven patients with chronic hepatitis C were treated with interferon beta at doses of 3 x 10(6) to 9 x 10(6) IU/day for 8 wk. The activities of 7-methoxycoumarin O-demethylase and 7-ethoxycoumarin O-deethylase in specimens obtained by liver biopsy were examined before and after interferon treatment. Theophylline pharmacokinetics were also examined before and after interferon treatment. Interferon beta treatment reduced the activities of both O-dealkylases from 6.0 (100%) to 3.2 (53%) nmol/gm liver per minute and from 1.9 (100%) to 1.1 (58%) nmol/gm liver per minute, respectively (p < 0.05). The total body clearance of theophylline was also decreased (from 0.76 to 0.56 ml/kg/min; p < 0.05), and its elimination half-life was increased (from 8.4 to 11.7 hr; p < 0.05); however, the volume of distribution was not significantly affected. The magnitude of the decreases in enzyme activities and in theophylline clearance varied widely in individual patients and did not correlate with the dose of interferon administered. This study provides the first direct evidence that interferon beta can depress the activity of drug-metabolizing enzymes in the human liver.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1993

Escape from redox regulation enhances the transforming activity of Fos.

Fos and Jun form dimeric complexes that bind to DNA sequences containing activator protein 1 (AP-1) sites and regulate gene expression. The in vitro DNA-binding activity of these proteins is sensitive to reduction-oxidation (redox). Reduction of a single conserved cysteine residue, located in the DNA-binding domain, either by reducing agents or by a nuclear redox factor (Ref-1), is required for AP-1 DNA-binding activity. Replacing the critical cysteine with serine results in a protein that can bind to DNA in vitro even under oxidizing conditions. To determine whether redox control affects the function of Fos in vivo, we have constructed, and compared the properties of, retroviral vectors expressing either a truncated Fos protein (F118-211) or a truncated Fos protein in which the critical cysteine was replaced by serine (FC154S). In infected chicken embryo fibroblasts (CEFs), both vectors expressed similar levels of Fos protein, which formed heterodimers with Jun at equivalent efficiencies. However, extracts from cells expressing FC154S exhibited a threefold increase in AP-1 DNA-binding activity compared with cells expressing F118-211. Furthermore, this enhanced binding activity was resistant to treatment with the oxidizing agent diamide. Infection of CEFs by virus expressing FC154S resulted in increased numbers of transformed colonies and an increase in colony size compared with those obtained following infection by virus expressing Fos 118-211. These results suggest that redox regulation may limit the total level of functional Fos-Jun complexes in vivo and that escape from this control enhances transforming activity.

Animals↗
PubMed1993

[Clinical significance of multiple mucosal biopsies in new cases of superficial papillary bladder tumor].

We assessed the clinical significance of multiple mucosal biopsies in new cases of superficial papillary bladder tumor. Biopsy findings were abnormal (5 dysplasia, 5 transitional carcinoma) in 10 of the 71 cases examined. Abnormalities were observed exclusively at G2 or G3, and more frequently at pT1 than pTa. Cases with multiple tumors showed significantly more abnormalities than cases with a solitary tumor. Recurrence rates were not significantly different between the cases with abnormal biopsy findings and those with normal findings. However, the invasive tumor developed more frequently in the former. Mucosal biopsies seemed to be more useful in cases with multiple tumors than in those with a solitary tumor.

Adult↗
PubMed1992

Inhibition of deoxyribonucleic acid synthesis in vitro by anticancer platinum pyrimidine greens against Daudi cells.

Platinum pyrimidine greens inhibited the deoxyribonucleic acid (DNA) synthesis of tumor cells in the S phase of the cell cycle and exerted antitumor activity. Clear differences were observed in the activity between the samples prepared at 40 degrees C and at 75 degrees C. Using 3H-thymidine incorporation assay and cell cycle analysis we confirmed that the former had much stronger and more specific inhibitory activity against DNA synthesis than the latter. Reactivity of the 40 degrees C sample with deoxyguanosine monophosphate (dGMP) and deoxyadenosine monophosphate (dAMP) was, respectively, two and three times larger than that of the 75 degrees C sample.

Antineoplastic Agents↗
PubMed1992

[Long-term outcome of cryptorchism after orchiopexy].

The long-term outcome of cryptorchism (undescended testis) was studied in 43 patients who underwent orchidopexy at pre-puberty ages and who were over 15 years of age at the time of this study. The follow-up period after operation was 11 approximately 23 years. Cryptorchism was unilateral in 39 patients and bilateral in 4 patients. The sperm concentration and motility were examined, using a cut-off level of 20 x 10(6)/ml for sperm concentration and 50% for sperm motility. In the unilateral cryptorchism group, 16 patients (61.5%) had normal semen quality, 8 patients (30.8%) oligozoospermia, 1 (3.8%) asthenozoospermia and 1 (3.8%) azoospermia. In the bilateral cryptorchism group, 3 patients (75.0%) were normal and 1 (25.0%) had azoospermia. Eight patients with unilateral cryptorchism were married and 7 of them (87.5%) had children. The sperm concentration had no inverse correlation with the age at operation. In patients with unilateral cryptorchism, the testicular volume on the healthy side was significantly higher than that on the affected side. The sperm concentration tended to correlate with the testicular volume on the healthy side rather than that on the affected side. These findings suggest that the sperm profiles in patients with unilateral cryptorchism are chiefly associated with the testicular function on the healthy side.

Adolescent↗
PubMed1992

[Cell culture and its application. Application of cultured vascular endothelial cells to the in vitro assay for the invasion of cancer cells through endothelium-matrix membrane system].

Usefulness of cultured human vascular endothelial cells for the in vitro assay of cancer invasion was reviewed. Selective isolation procedures for the vascular endothelial cells from the different types of vascular tubes were described. Human umbilical cord vein is one of the most useful sources for the isolation of fresh normal endothelial cells. The cells are isolated by perfusing trypsin solution through the umbilical cord vein and successively subcultivated up to 80 population doubling levels as in vitro life span. In case of human thoracic aorta, endothelial cells were removed from endothelium layer of aorta ring by a jet flow of collagenase solution through a needle. Purity of these cells as endothelial cells can be determined by indirect staining of the cytoplasma with anti-endothelin antibody. Usefulness of these cultured endothelial cells has been proved in the studies of regulation of endothelin biosynthesis, ageing of vascular cell, isolation of some new growth factors, interaction with other blood cells, etc. In addition to these studies, we consider that interaction of tumor cells with endothelial cells plays an important role in tumor metastasis. So we established in vitro invasion assay system through the interaction with endothelial cells to examine the invasion and adhesion of tumor cells. Human umbilical cord endothelial cells (HUVEC) were cultured on porous membranes coated with laminin (LN). HT1080 fibrosarcoma cells were seeded onto HUVEC, and HT 1080 cells passed through the membrane were counted. HUVEC were easily distinguished from tumor cells by specific staining of endothelial cells with UEA-1 lectin. Using scanning electron microscopy, we confirmed that HT1080 cells invaded between HUVEC. Roles of adhesion molecules induced by some cytokines on invasion of cancer cells through the endothelial cells-matrix membrane system were discussed.

Cell Adhesion↗
PubMed1992

[A case of hematuria associated with cefem group antibiotics].

The patient was a 76-year-old male with disturbance of consciousness due to cerebral infarction. He was found lying in his garden on July 30, 1990 and was immediately hospitalized. Central venous alimentation was started on the same day, because the patient was incapable of oral nutritional intake. Aspiration pneumonia developed on August 3. As Pseudomonas aeruginosa and Candida were detected by sputum cultures on August 20, antibiotics were changed to latamoxef (LMOX), 6 g/day, tobramycin, 180 mg/day, and fluconazole, 200 mg/day, from August 30. Macroscopic hematuria was noted after exchange of the urethral catheter. Hematuria gradually worsened, bladder tamponade occurred, and anemia had exacerbated with Hb decreasing from 13.4 to 8.7 g/dl and Hct from 39.1 to 26% on September 14, when the patient was referred to our department. Corresponding marked increases were observed in PT from 11.5 to 50.1 seconds and in APTT from 33.7 to 107.6 seconds. As the hematuria was suspected to be due to vitamin K deficiency hypoprothrombinemia induced by LMOX, its administration was discontinued on the day of the referral. Hematuria was alleviated from the next day, and PT normalized to 12.1 seconds and APTT to 36.6 seconds 3 days after discontinuation. The administration of vitamin K was started on this day, and hematuria disappeared 7 days after discontinuation of LMOX administration.

Aged↗
PubMed1991

Difference in transcriptional regulatory function between c-Fos and Fra-2.

Fra-2, one of the Fos-related antigens, is promptly expressed after the growth stimulation of fibroblasts, but its induction peak is later than that of c-Fos. In this report, we examined biochemical properties of Fra-2 and compared them with those of two other Fos family proteins, c-Fos and Fra-1. Like c-Fos and Fra-1, Fra-2 formed stable heterodimers with c-Jun, JunB or JunD in vitro and all these complexes had specific DNA-binding activity to AP-1-binding sites (AP-1 sites) or related sequences. When transiently introduced into a mouse embryonic carcinoma cell line, F9, with reporter genes containing the AP-1 site from the collagenase gene, fra-2 plus c-jun suppressed the transactivation by c-jun alone. This property of Fra-2 is in clear contrast to that of c-Fos, which stimulates the transcriptional activity of c-Jun by forming a stable heterodimer. Analysis of chimeric proteins between c-Fos and Fra-2 indicated that this difference is mainly attributable to their C terminal-half regions. Interestingly, this suppressive effect of Fra-2 was not observed in the combination with JunD: fra-2 plus junD, like c-fos plus junD, had higher transcriptional activity than junD alone. Fra-1 showed essentially the same transcriptional regulatory properties as Fra-2. These differential properties greatly expand the potential range of regulatory functions of the Fos family proteins.

Animals↗
PubMed1991

High-level expression of human c-jun gene causes cellular transformation of chicken embryo fibroblasts.

To analyze the transforming activity of c-jun, a Rous sarcoma virus (RSV) variant that carries human c-jun instead of v-src (JH1) was constructed. After infection onto chicken embryo fibroblasts (CEF), JH1 formed foci with a titer comparable to that of wild-type RSV, and the infected cells grew in soft agar, indicating that the human c-jun gene has transforming potential, like the v-jun gene. The expression of Fra-2, one of the recently isolated Fos-related antigens, but not Fos was detected in both JH1-infected CEF and CEF infected with the control retrovirus vector (DS3). Gel shift analysis using nuclear extracts from DS3-infected CEF revealed that the Fra-2/Jun complex contributes to the basal level of AP-1 DNA binding activity. A similar activity was detected in JH1-infected CEF, but these cells have an additional AP-1 binding activity derived from Jun homodimers that seems to play important roles in the cellular transformation.

Animals↗
PubMed1991

[A case of squamous cell carcinoma of the urinary bladder effectively responsive to combination chemotherapy].

A case of invasive pure squamous cell carcinoma of the urinary bladder effectively responsive to combination chemotherapy in a 79-year-old female is reported. Clinical staging of the tumor was T3b. We used combination chemotherapy with methotrexate, peplomycin and cis-platinum (MBD regimen) before radical cystectomy. Remarkable regression of the tumor was identified by computed tomographic scan after one course of chemotherapy and the surgical specimen revealed no viable tumors. The patient has been very active in her daily life without evidence of local recurrence or metastasis for more than one year. Squamous cell carcinoma of the bladder generally is regarded as having a poor prognosis with 5-year survival rates ranging from 7.4 to 26% and effective chemotherapy has not yet been established. Our experience suggests that the cure rate of pure squamous cell carcinoma may be improved markedly by the use of MBD regimen.

Aged↗
PubMed1991

Inhibition of jun transformation by a mutated fos gene: design of an anti-oncogene.

The protein products of the fos and jun oncogenes (Fos and Jun) function as transcriptional regulators in the form of homo- or heterodimeric complexes that bind to DNA. Dimerization is mediated by a leucine zipper structure that serves to juxtapose alpha-helical regions of each protein, rich in basic amino acids, that form a bipartite DNA-binding domain. Although Fos participates exclusively in heterodimeric complexes, Jun can function either as a homodimer that has a low apparent affinity for DNA or as a more stable heterodimer with Fos that has a higher apparent affinity for DNA. We have used these properties of Fos and Jun to design a mutated fos gene, lacking a functional DNA-binding domain (supfos1), that suppresses the transforming activity of jun in trans. Here we show that chicken embryo fibroblasts transformed by jun revert to a normal phenotype after infection by a retroviral vector encoding supFos1. Furthermore, infection of normal cells with the supfos1 vector renders them resistant to subsequent transformation by jun. Inhibition of jun transformation was associated with the appearance of supFos1-Jun heterodimers and a reduction in the AP-1 DNA-binding activity contributed by Jun homodimers. These findings demonstrate that the function of leucine zipper-containing transcription factors can be investigated by the procedure of intracellular immunization.

Animals↗
PubMed1990

Depression of drug metabolizing activity in the human liver by interferon-alpha.

The depressant effect of interferon-alpha on drug metabolizing activity in the liver has been investigated in 12 patients with chronic active hepatitis B. 7-methoxy-coumarin (7-MC) O-demethylase and 7-ethoxycoumarin (7-EC) O-deethylase, in specimens obtained by liver biopsy, were measured before and after interferon treatment. 7-MC and 7-EC O-dealkylase activity were significantly reduced after interferon treatment, from 13.4 to 9.24 nmol.g-1 liver.min-1, and from 3.22 to 2.16 nmol.g-1 liver.min-1, respectively. The magnitude of the fall varied widely between individual patients. The study provides the first direct evidence that interferon-alpha can impair the activity of drug metabolizing enzymes in the human liver.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1990

Audiological findings of prolonged Menière's disease.

As Ménière's disease progresses, the fluctuations becomes less marked and the hearing level gradually declines. In the more established and advanced stages of the disease, a permanent and progressive hearing loss develops. It has been reported, however, that hearing acuity in some patients with Ménière's disease significantly improved after having had the disorder for many years. Such observation suggests that the inner ear pathology in late stages of Ménière's disease may not be necessarily irreversible. The purpose of this investigation was to assess whether or not various audiological evaluations including EcochG may be of value in predicting the irreversibility of hearing deficit in patients suffering from advanced stages of Ménière's disease. The audiological studies included pure tone audiogram, SISI test, Bekesy audiometry, glycerol (or urea) test, speech discrimination test, and electrocochleography. A combination of the recruiting type of response in the EcochG and the narrowing of the tracing width of continuous sound in the Bekesy pattern seemed to be indicative for irreversible hair cell damages. Patients who had a low score in the speech discrimination test as well as an absence of ABR response were suspected of having retrocochlear lesions. Our investigations suggest that the irreversibility of hearing impairment in patients with later stages of Ménière's disease may be predicted to some extent in the use of various audiological evaluations including the EcochG.

Adult↗