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Biomedical subjects

K Oka

Publications and source records attributed to K Oka.

At least 199 records · Page 11Linked to original sources
PubMed1997

Relative changes of MIB1 and PC10 labeling indexes in cell kinetics during radiotherapy for cervical squamous cell carcinoma.

To assess the changes in cell kinetics during radiotherapy (RT) in terms of the MIB1 and PC10 labeling indexes of cancer cells, a total of 230 biopsy specimens taken from 76 consecutive patients with cervical squamous cell carcinoma treated with RT was investigated. The MIB1 and PC10 indexes represent the growth fraction and proliferative activity, respectively. The MIB1 index ranged from 11 to 67% (mean value: 38%) before RT, from 21 to 86% (50%) at 5.4 Gy, from 15 to 85% (53%) at 9 Gy, and from 0 to 69% (26%) at 27 Gy. The PC10 index ranged from 4 to 46% (23%) before RT, from 5 to 62%, (26%) at 5.4 Gy, from 6 to 63% (23%) at 9 Gy, and from 0 to 35% (11%) at 27 Gy. The correlational relationships between the increment of both indexes during RT (delta index) and the index before RT were analyzed on an individual basis. The delta index was calculated by the index at various doses during RT minus the index before RT. Negative linear relationships were observed between the delta MIB1 index at 9 Gy or delta MIB1 index at 27 Gy and the MIB1 before RT, and also between the delta PC10 index at 9 Gy or delta PC10 index at 27 Gy and the PC10 index before RT. The linear regression coefficient values showed more than 0.5 (0.511 to 0.682) with statistical significance. According to these results, it was suggested that the cervical cancers of lower proliferative activity showed greater increases in growth fraction and proliferative activity by irradiation than those of higher proliferative tumors. These findings suggest that reversal patterns of changes in cell kinetics including growth fraction and proliferative activity took place in the early period of RT for cervical squamous cell carcinomas. The study of changes in cell cycle kinetics in human tumors during RT may have potential impact on the further development of RT.

Adult↗
PubMed1997

Factors affecting induction of neurological disorder in mice by PVC viruses and the sequence of env-LTR region of PVC441.

PVC111, PVC211, PVC321 and PVC441 cause neurological disorders associated with tremor and paralysis in rats. We tested the pathogenicity of these viruses in mice. Although histopathological studies revealed spongiform degeneration in the spinal cords of NFS mice infected with each PVC virus, only PVC441 caused a high incidence of tremor and paralysis. Further studies with PVC441 revealed dose and age dependence for tremor induction. In contrast to NFS mice, BALB/c, DBA/2 and C57BL/6 mice infected with PVC441 virus showed no neurological symptoms, although the virus replicated in each strain to titers within 5-fold of the titer in NFS mice. Despite absence of neurological symptoms, high degree of neuronal degeneration in the lumbar spinal cord was found in PVC441-infected BALB/c mice. Low degree of neuronal degeneration was found in PVC441-infected DBA/2 or C57BL/6 mice. Genetic crosses of these resistant mice with susceptible NFS mice indicated that resistance to PVC441-induced tremor induction was dominant in all strains and suggested that various host genes may control the susceptibility of mice to tremor induction by PVC441 virus. Sequencing of env-LTR region of PVC441 revealed an intermediate character between PVC211 and F-MuLV.

Animals↗
PubMed1997

Histopathological studies on spontaneous vault moyamoya and revascularized collaterals formed by encephalomyosynangiosis.

Two topics concerning the leptomeningeal vessels are discussed. The first portion indirectly proves that angiographic 'vault Moyamoya' consists of dilated preexisted vessels rather than newly-formed vessels, using morphometric analysis. The second portion presents a 67 year old autopsied case with Moyamoya disease who underwent encephalomyosynangiosis (EMS). Collateral vessels fomred by EMS are histopathologically identified.

Adolescent↗
PubMed1997

Evaluation of transrectal voiding ultrasonography in men with micturition difficulties without apparent organic obstruction of the lower urinary tract.

OBJECTIVE: To examine whether transrectal voiding ultrasonography (TRVUS) can evaluate voiding movement in men with dysfunctional voiding. METHODS: Ninety-nine consecutive men complaining of voiding difficulties without benign prostatic hyperplasia, prostatic cancer, severe bladder neck contracture and urethral stricture received uroflowmetry and TRVUS. Those who had abnormal findings on both uroflowmetry and TRVUS underwent subsequent cystometry combined with electromyography (EMG) to confirm the presence of dysfunctional voiding. RESULTS: Uroflowmetry indicated abnormal findings in 31 of the 99 patients, and TRVUS demonstrated abnormal movements of the posterior urethra during voiding in all of these 31 patients and 11 of the other 68 patients whose uroflowmetry did not indicate abnormality. TRVUS findings of the former 31 were divided into type E (the external urethral sphincter closed or intermittently opened while the bladder neck manifested an opening movement of > 7 mm during voiding in 20) and type I (both the bladder neck and external urethral sphincter manifested an intermittent movement of < 7 mm in 11). Subsequent cystometry combined with EMG in the 31 patients who had abnormal findings on both uroflowmetry and TRVUS revealed overactivity of the external urethral sphincter (OS) and underactivity of the detrusor (UD) in 85 and 35% of type-E group and 55 and 73% of type-I group, respectively. Type E included significantly more OS without UD than type I (65 vs. 18%; p = 0.0233). All of type-E (20/20) and 91% of type-I (10/11) patients had voiding difficulty which resulted from either OS or UD, while a very limited number of patients (4/31) manifested neurological symptoms such as paraplegia except for voiding difficulties. CONCLUSIONS: Both uroflowmetry and TRVUS are easy and useful methods to evaluate dysfunctional voiding in men, especially when neural disorders or organic obstruction of the lower urinary tract are not apparent.

Aged↗
PubMed1997

Production of rabbit polyclonal antibody against apobec-1 by genetic immunization.

Circulating apolipoprotein B (apoB) exists in two forms; apoB-100 and apoB-48. ApoB-48 is a truncated form of apoB resulting from RNA editing. The editing enzyme, called apobec-1, converts a cytidine (C) at nucleotide 6666 in apoB 100 mRNA to a uridine (U) and changes a CAA codon to an in-frame stop codon, UAA. We have produced a specific rabbit polyclonal antiserum against apobec-1 by genetic immunization. The cDNA of mouse apobec-1 was inserted downstream and in-frame at the BamH I site in the last exon of human growth hormone cDNA driven by a cytomegalovirus promoter. This plasmid was injected together with another plasmid expressing granulocyte macrophage colony-stimulating factor into the thigh muscles of a rabbit. The resulting antiserum demonstrated high specificity on Western blots, and inhibited the apoB mRNA editing activity of mouse liver extract in a dose-dependent manner. This report demonstrates that DNA immunization is a powerful technique that can be readily applied to other sparse or difficult-to-purify proteins in lipid metabolism.

APOBEC-1 Deaminase↗
PubMed1996

Invasive pattern of lac-Z-transfected human glioblastoma cells in nude mice brain.

Primary, malignant brain tumors show an extensive infiltrative invasion into surrounding normal brain. At present, little information is available regarding the local invasive behavior of human brain tumors and until now no animal model suitable to mimic human gliomas has been reported. To identify the infiltrative behavior of an established glioblastoma cell line (SNB19), we achieved a stable transfection of the SNB19 cell line with beta-galactosidase (lac-Z) plasmid. The stable beta-galactosidase-expressing cells were then injected intracerebrally into nude mice in an attempt to follow its pattern of spread. The mice were sacrificed at 3, 4, and 6 weeks postinjection. We could detect tumor formation in all of the animals, and the tumor size increased gradually over the 6 week time period. Three weeks after injection, tumor cells showed characteristic infiltrative invasion along the corpus callosum. We also observed tumor-cell invasion into the anterior commissure in some animals, and each tumor cell could be identified by lac-Z expression as visualized by its blue color. Further invasion was identified at 4 and 6 weeks postinjection. Our results suggest that this model could be used to study the molecular mechanisms involved in the invasion of gliomas so that appropriate therapeutic intervention strategies could be designed.

Animals↗
PubMed1996

Transcription of the human hepatic lipase gene is modulated by multiple negative elements in HepG2 cells.

The expression of the hepatic lipase (HL) gene is highly tissue specific. In order to identify cis-acting elements which regulate the expression of this gene in the liver, multiple deletion mutants of the 5'-flanking region of the HL gene fused to the human growth hormone gene were transfected in HepG2 cells, which normally produce HL. Transient expression assays indicated the presence of negative (at nucleotides (nt) -1576(/)-1342 and -623(/)-407) and positive (at nt -1862(/)-1576 and -50(/)-9) regulatory elements. Transfection of HeLa cells, which do not produce HL, with the same deletion constructs resulted in a similar pattern of promoter activities. However, additional negative (nt -138/-50) and positive (nt -407(/)-138) elements were found. DNase I footprint analysis of the proximal and distal HLpromoter sequences with HepG2 and HeLa cell nuclear extracts identified seven protected regions: A, nt -1540(/)-1527; B, -1505(/)-1473; C, -1467(/)-1460; D, -592(/)-577; E, -565(/)-545; F, -234(/)-220; and G, -70(/) -48. Sites A, B, C, D and E were located within regions containing negative regulatory elements. In order to determine which nuclear factor interacts with the negative elements, sites B, D and E were mutated and the effects of mutation on competition in a gel retardation assay and on promoter activity were studied. When the binding motif for AP1 in sites B, D and E was mutated, the specific DNA-protein complexes were not competed with the mutant oligonucleotides and promoter activity increased twofold. The magnitude of the increase is less than expected from the deletion analysis, and simultaneous mutations did not cause further increase in promoter activity, which suggests that other sites are involved in this negative modulation. These results suggest that the transcription of the HLgene in HepG2 cells is negatively modulated by multiple cis-acting negative elements and AP1-like nuclear factor may play some role in this modulation.

Base Sequence↗
PubMed1996

Dendritic Ca2+ response in cercal sensory interneurons of the cricket Gryllus bimaculatus.

In order to understand dendritic information processing, we examined spatio-temporal pattern of intracellular Ca2+ changes in cercal sensory interneurons of the cricket. We used a fluorescent imaging technique with confocal laser-scanning microscopy and a fluorescent calcium indicator, "Calcium Green 1'. Electrical stimulation of cercal sensory nerves induced Ca2+ increase on local dendritic regions in these interneurons. The Ca2+ responses in several dendritic arborizations differed from each other in their amplitude, latency and duration, depending on direction that the cercal nerve was stimulated. These results suggest that synaptic inputs coding directional wind signals are topographically arranged on the dendrite, and that the dynamics of Ca2+ accumulation contribute to integrative processing of the synaptic inputs.

Animals↗
PubMed1996

Complete phenotypic characterization of apobec-1 knockout mice with a wild-type genetic background and a human apolipoprotein B transgenic background, and restoration of apolipoprotein B mRNA editing by somatic gene transfer of Apobec-1.

We have produced gene knockout mice by targeted disruption of the apobec-1 gene. As recently reported by Hirano et al. (Hirano, K.-I., Young, S. G., Farese, R. V., Jr., Ng, J., Sande, E., Warburton, C., Powell-Braxton, L. M., and Davidson, N. O. (1996) J. Biol. Chem. 271, 9887-9890), these animals do not edit apolipoprotein (apo) B mRNA or produce apoB-48. In this study we have performed a detailed analysis of the lipoprotein phenotypic effects of apobec-1 gene disruption that were not examined in the previous study. We first analyzed the plasma lipoproteins in knockout animals with a wild-type genetic background. Although there was no difference in plasma cholesterol between apobec-1(-/-), +/-, or +/+ mice, there was a marked (176%) increase in plasma apoB-100, from 1.8 +/- 1.2 mg/dl in apobec-1(+/+) mice to 2.7 +/- 0.6 mg/dl in apobec-1(+/-) and 5.0 +/- 1.4 mg/dl in apobec-1(-/-) mice. Plasma apoE was similar in these animals. By fast protein liquid chromatography (FPLC) analysis, there was a significant decrease in plasma high density lipoprotein (HDL) cholesterol in apobec-1(-/-) mice. We further fractionated the plasma lipoproteins into d < 1.006, 1.006-1.02, 1.02-1.05, 1.05-1.08, 1.08-1.10, and 1.10-1.21 g/ml classes, and found a marked (30-40%) reduction in the cholesterol and protein content in the (d 1.08-1.10 and 1.10-1.21) HDL fractions, corroborating the FPLC data. SDS-gel analysis revealed an absence of apoB-48, an increase in apoB-100 in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions, and a small decrease in apoA-I in the HDL fractions in the apobec-1(-/-) samples. We next raised the basal plasma apoB levels in the apobec-1(-/-) animals by cross-breeding them with human apoB transgenic (TgB) mice. The plasma apoB-100 was 3-fold higher in apobec-1(-/-)/TgB+/- mice (26.6 +/- 18.3 mg/dl) than in apobec-1(+/+)/TgB+/- mice (9.8 +/- 3.9 mg/dl, p < 0.05). The apobec-1(-/-)/TgB+/- mice had a plasma cholesterol levels of 170 +/- 28 mg/dl and triglyceride levels of 106 +/- 31 mg/dl, which are 80% and 58% higher, respectively, than the corresponding values of 94 +/- 21 mg/dl and 67 +/- 11 mg/dl in apobec+/+/TgB+/- mice. By FPLC, the apobec-1(-/-)/TgB+/- animals developed markedly elevated plasma LDL cholesterol (518.5 +/- 329.5 microg/ml) that is 373% that of apobec1(+/+)/TgB+/- mice (139.0 +/- 87.0 microg/ml) (p < 0.05). The elevated plasma triglyceride was accounted for mainly by a 97% increase in VLDL triglyceride in the apobec1(-/-)/TgB+/- mice. We conclude that apobec-1(-/-) animals have a distinctive lipoprotein phenotype characterized by significant hyperapoB-100 and HDL deficiency in mice with a wild-type genetic background. Furthermore, the abolition of apoB mRNA editing elevates plasma total cholesterol and LDL cholesterol in apobec-1(-/-) animals with a TgB background. Finally, to exclude the possibility that absence of apoB mRNA editing was a secondary effect of chronic Apobec-1 deficiency, we treated apobec-1(-/-) mice with a replication-defective mouse Apobec-1 adenoviral vector and found that we could acutely restore apoB mRNA editing in the liver. These experiments indicate that Apobec-1 is an essential component of the apoB mRNA editing machinery and absence of editing in the knockout animals is a direct consequence of the absence of functional Apobec-1.

APOBEC-1 Deaminase↗
PubMed1996

Inhibition of peripheral interleukin-1 beta-induced hyperalgesia by the intracerebroventricular administration of diclofenac and alpha-melanocyte-stimulating hormone.

The present study was undertaken to investigate whether or not the endogeneous mechanisms in the brain can modulate the changes in nociception produced by peripherally-administered interleukin-1 beta (IL-1 beta) in rats. We administered diclofenac and alpha-melanocyte-stimulating hormone (alpha-MSH) into the lateral cerebroventricle (LCV) 10 min before the intraperitoneal (i.p.) injection of recombinant human IL-1 beta (rhIL-1 beta, 1 ng/kg-100 ng/kg) and then observed the changes in nociception using a hot-plate test. The i.p. injection of rhIL-1 beta (10 ng/kg and 100 ng/kg) reduced the paw-withdrawal latency without affecting the colonic temperature. The maximal reduction in the paw-withdrawal latency was observed 30 min after the i.p. injection of rhIL-1 beta at 100 ng/kg. The rhIL-1 beta (100 ng/kg)-induced hyperalgesia was inhibited by the LCV injection of both diclofenac (1 ng) and alpha-MSH (100 ng). The LCV injection of either diclofenac (1 ng) or alpha-MSH (100 ng) was found to have no effect on nociception by itself. These findings therefore suggest that the hyperalgesia induced by peripheral IL-1 beta can be modulated by a cyclooxygenase pathway of the arachidonate and alpha-MSH in the brain.

Animals↗
PubMed1996

Manganese superoxide dismutase expression correlates with p53 status and local recurrence of cervical carcinoma treated with radiation therapy.

Manganese superoxide dismutase (Mn-SOD) inactivates the radiation effect by removal of radiation-induced toxic superoxide radicals. The purpose of this study was to assess the correlation among Mn-SOD, radiation sensitivity, and prognosis following radiation therapy. The Mn-SOD, p53 oncoprotein, and c-erbB-2 oncoprotein expressions in 52 specimens from patients with cervical cancer treated with radiation therapy were investigated immunohistochemically. The frozen sections were stained using antihuman Mn-SOD, anti-p53 monoclonal antibodies, and anti-c-erbB-2 oncoprotein polyclonal antibody followed by the avidin-biotin peroxidase complex method. Correlations among Mn-SOD expression, prognosis, and failure patterns were analyzed. Additionally, correlations between p53 and c-erbB-2 oncoproteins and Mn-SOD expression were investigated. Positive expression of Mn-SOD in cervical carcinoma was 48.1%. No significant difference in positivity of Mn-SOD expression was noted according to stage and histological subtypes. The 5-year survival rate of Mn-SOD-positive patients was 42.5 %, significantly poorer than the 77.0% of Mn-SOD-negative patients (P < 0.05). Analysis of the failure patterns revealed that patients with Mn-SOD expression showed a significantly higher incidence of local recurrence than those without. However, there was no difference in distant metastasis between them. Although both p53 and c-erbB-2 oncoprotein expressions were significantly associated with the prognosis of the same patients, Mn-SOD expression was associated with p53 oncoprotein expression but not with that of c-erbB-2 oncoprotein. Our results demonstrate that the Mn-SOD level of cancer cells is correlated with local control and is an important prognostic factor in radiation therapy for cervical cancer. The Mn-SOD level may help explain the intrinsic radiosensitivity of cervical cancer cells.

Carcinoma, Squamous Cell↗
PubMed1996

Analysis of response to radiation therapy of patients with cervical adenocarcinoma compared with squamous cell carcinoma. MIB-1 and PC10 labeling indices.

BACKGROUND: The MIB-1 monoclonal antibody is a marker of cycling cells and the PC10 monoclonal antibody is a marker of proliferating cell nuclear antigen in paraffin sections. This study was conducted to elucidate the difference in response to radiotherapy (RT) between cervical adenocarcinomas and squamous cell carcinomas, focusing on cell proliferation. METHODS: A total of 196 biopsy specimens taken from the cervical carcinomas of 14 consecutive patients with adenocarcinoma and 62 patients with squamous cell carcinoma before and after RT at doses of 9 and 27 Grays (Gy) were investigated for MIB-1 and PC10 immunoreactivities. RESULTS: In adenocarcinomas, the mean MIB-1 labeling indices before and after RT at 9 and 27 Gy were 28%, 21%, and 26%, respectively, whereas the mean PC10 labeling indices were 15%, 13%, and 14%, respectively. In squamous cell carcinomas, the mean MIB-1 labeling indices before and after RT at 9 and 27 Gy were 38%, 53%, and 26%, respectively, and the mean PC10 labeling indices were 23%, 23%, and 11%, respectively. CONCLUSIONS: Cervical adenocarcinomas have a lower cycling cell population and their indices show no change during RT. Squamous cell carcinomas have a higher cycling cell population and show a transient increase of the MIB-1 cycling cell population at 9 Gy of RT. These findings suggest a difference in response to RT between adenocarcinomas and squamous cell carcinomas.

Adenocarcinoma↗