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Biomedical subjects

K Oka

Publications and source records attributed to K Oka.

At least 109 records · Page 6Linked to original sources
PubMed1999

Optical monitoring of the neural activity evoked by mechanical stimulation in the earthworm nervous system with a fluorescent dye, FM1-43.

In the central nervous system of the earthworm, sensory and motor neurons have direct synapses on three giant fibers. To determine the locations of synapses and neural network activated by mechanical stimuli, we optically monitored the activity-dependent staining in the earthworm ventral nerve cord with a styryl dye, N-(3-triethylammoniumpropyl)-4- (4-(dibutylamino)styryl)pyridinium dibromide (FM1-43), and a confocal laser scanning microscope. When scratch stimulus was applied to the body wall of the earthworm, bright fluorescent spots with 3-10 microns in diameter localized only in the stimulated segmental ganglion of the ventral nerve cord. The fluorescent intensity of these spots decreased during dye-free high K+ saline incubation. These results suggest that FM1-43 is useful for activity-dependent staining of invertebrate neurons and their synaptic regions as well as vertebrate nervous system.

Animals↗
PubMed1999

Relationship between p21/WAF-1/CIP-1 and apoptosis in cervical cancer during radiation therapy.

PURPOSE: P21/WAF-1/CIP-1 was not considered to be involved in the regulation of apoptosis, an important indicator of radiosensitivity. However, it has been reported recently that apoptosis was suppressed when p21 expressed. The purpose of this study was to clarify the relationship between p21 and apoptosis and to evaluate the role of p21 in cervical cancer during radiation therapy (RT). METHODS AND MATERIALS: Twenty-one patients with cervical cancer were treated by RT. Tissue samples were obtained from cervical tumors of all patients before RT, and 6 hours after the fifth dose of 1.8 Gy (5th Dose). Samples were subjected to nick end labeling for apoptosis and immunohistochemical staining for p21 and p53 antigen expression. RESULTS: The mean apoptotic index, p21 labeling index and p53 labeling index were 0.27%, 9.24% and 6.60%, respectively, before RT and increased significantly to 1.20%, 17.5% and 13.9%, respectively, after 5th Dose. The apoptotic index at 5th Dose was inversely correlated with the p21 labeling index (r = -0.50, p = 0.025). Furthermore, a positive correlation was observed between the p21 and p53 labeling indices both before RT and at 5th Dose (r = 0.52, p = 0. 02; r = 0.63, p < 0.01, respectively). CONCLUSION: Our results demonstrate that apoptosis and expression of p21 and p53 were induced in cervical cancer during RT. p21 expression was dependent on p53 expression and moreover, it is suggested-that p21 might be a potential suppressor of radiation-induced apoptosis in cervical cancer during RT.

Aged↗
PubMed1999

Concurrent three dimensional neuroendoscopy: initial descriptions of application to clinical practice.

Applications of endoscopic technique neurosurgery are becoming increasingly popular as greater evidence of the safety and efficacy of these techniques is reported. Nevertheless, significant technical limitations need to be solved before neuroendoscopy can achieve widespread popularity. One limitation is the surgeon's difficulties in becoming anatomically oriented in a two-dimensional (2-D) environment. The lack of appropriate visual cues to orient oneself in three-dimensional (3-D) space makes relatively simple anatomical regions difficult to navigate. The authors describe an endoscopy system that allows for stereoscopic visualization during minimally invasive procedures and that acts as an adjunct to conventional open craniotomies. Four cases are described in which stereoendoscopy was used as either a primary means of visualization or as an adjunct to the operating microscope in conventional open neurosurgical procedures. The authors believe that stereoendoscopic vision is a significant advance in endoscope technology and will play a large role in the popularization of minimally invasive techniques in neurosurgery.

Journal Article↗
PubMed1999

Tumorigenic conversion resulting from inhibition of apoptosis in a nontumorigenic HeLa-derived hybrid cell line.

Although tumorigenicity in nude mice is one of the most important transformed phenotypes, its mechanism has been little analyzed. To understand the molecular basis of tumorigenicity, we characterized nontumorigenic CGL1 and tumorigenic CGL4 cell lines, both of which were originated from a common ancestral HeLa-human diploid fibroblast hybrid cell clone and retained a malignant state except tumorigenicity. When injected into nude mice, nontumorigenic CGL1 cells underwent apoptosis, but tumorigenic CGL4 cells did not. In vitro, CGL1 was also less resistant to various apoptotic stimuli than CGL4. These results suggested that inhibition of apoptosis may lead to tumorigenicity. To examine this hypothesis, we introduced antiapoptotic genes into the CGL1 cell line and injected the resulting clones into nude mice. The results showed that the ectopic expression of Bcl-2 or E1B19k, but not of crmA, converted CGL1 cells to tumorigenicity, suggesting strongly that this phenotype may be conferred by evasion of apoptosis.

Animals↗
PubMed1999

Ligand binding properties of the very low density lipoprotein receptor. Absence of the third complement-type repeat encoded by exon 4 is associated with reduced binding of Mr 40,000 receptor-associated protein.

The very low density lipoprotein receptor (VLDLR) binds, among other ligands, the Mr 40,000 receptor-associated protein (RAP) and a variety of serine proteinase-serpin complexes, including complexes of the proteinase urokinase-type plasminogen activator (uPA) with the serpins plasminogen activator inhibitor-1 (PAI-1) and protease nexin-1 (PN-1). We have analyzed the binding of RAP, uPA.PAI-1, and uPA.PN-1 to two naturally occurring VLDLR variants, VLDLR-I, containing all eight complement-type repeats, and VLDLR-III, lacking the third complement-type repeat, encoded by exon 4. VLDLR-III displayed approximately 4-fold lower binding of RAP than VLDLR-I and approximately 10-fold lower binding of the most C-terminal one of the three domains of RAP. In contrast, the binding of uPA.PAI-1 and uPA.PN-1 to the two VLDLR variants was indistinguishable. Surprisingly, uPA.PN-1, but not uPA.PAI-1, competed RAP binding to both VLDLR variants. These observations show that the third complement-type repeat plays a crucial role in maintaining the contact sites needed for optimal recognition of RAP, but does not affect the proteinase-serpin complex contact sites, and that two ligands can show full cross-competition without sharing the same contacts with the receptor. These results elucidate the mechanisms of molecular recognition of ligands by receptors of the low density lipoprotein receptor family.

Animals↗
PubMed1999

Reversal of hyperlipidaemia in apolipoprotein C1 transgenic mice by adenovirus-mediated gene delivery of the low-density-lipoprotein receptor, but not by the very-low-density-lipoprotein receptor.

We have shown previously that human apolipoprotein (apo)C1 transgenic mice exhibit hyperlipidaemia, due primarily to an impaired clearance of very-low-density lipoprotein (VLDL) particles from the circulation. In the absence of at least the low-density-lipoprotein receptor (LDLR), it was shown that APOC1 overexpression in transgenic mice inhibited the hepatic uptake of VLDL via the LDLR-related protein. In the present study, we have now examined the effect of apoC1 on the binding of lipoproteins to both the VLDL receptor (VLDLR) and the LDLR. The binding specificity of the VLDLR and LDLR for apoC1-enriched lipoprotein particles was examined in vivo through adenovirus-mediated gene transfer of the VLDLR and the LDLR [giving rise to adenovirus-containing (Ad)-VLDLR and Ad-LDLR respectively] in APOC1 transgenic mice, LDLR-deficient (LDLR-/-) mice and wild-type mice. Remarkably, Ad-VLDLR treatment did not reduce hyperlipidaemia in transgenic mice overexpressing human APOC1, irrespective of both the level of transgenic expression and the presence of the LDLR, whereas Ad-VLDLR treatment did reverse hyperlipidaemia in LDLR-/- and wild-type mice. On the other hand, Ad-LDLR treatment strongly decreased plasma lipid levels in these APOC1 transgenic mice. These results suggest that apoC1 inhibits the clearance of lipoprotein particles via the VLDLR, but not via the LDLR. This hypothesis is corroborated by in vitro binding studies. Chinese hamster ovary (CHO) cells expressing the VLDLR (CHO-VLDLR) or LDLR (CHO-LDLR) bound less APOC1 transgenic VLDL than wild-type VLDL. Intriguingly, however, enrichment with apoE enhanced dose-dependently the binding of wild-type VLDL to CHO-VLDLR cells (up to 5-fold), whereas apoE did not enhance the binding of APOC1 transgenic VLDL to these cells. In contrast, for binding to CHO-LDLR cells, both wild-type and APOC1 transgenic VLDL were stimulated upon enrichment with apoE. From these studies, we conclude that apoC1 specifically inhibits the apoE-mediated binding of triacylglycerol-rich lipoprotein particles to the VLDLR, whereas apoC1-enriched lipoproteins can still bind to the LDLR. The variability in specificity of these lipoprotein receptors for apoC1-containing lipoprotein particles provides further evidence for a regulatory role of apoC1 in the delivery of lipoprotein constituents to different tissues on which these receptors are located.

Adenoviridae↗
PubMed1999

Reduction of syndecan-1 mRNA in cervical-carcinoma cells is involved with the 3' untranslated region.

Syndecan-1 is a transmembrane proteoglycan expressed predominantly in epithelial cells. Studies with immunohistochemistry have shown that syndecan-1 expression is reduced in carcinoma derived from human epidermis. Here we show that syndecan-1 mRNA, which is abundant in human primary keratinocyte (HK) and HaCaT spontaneous immortalized keratinocyte, is decreased in cervical-carcinoma cell lines. Further, in relation to a long and well-conserved 3' untranslated region (3' UTR) of syndecan-1 cDNA, we examined whether 3' UTR is involved with syndecan-1-mRNA reduction in cervical-carcinoma cells. A stable transfection experiment showed that addition of the 3' UTR does not affect expression in HaCaT, but that syndecan-1 cDNA containing the 3' UTR is not expressed efficiently selectively in cervical-carcinoma cell lines. The transient assay with CAT reporter plasmids linking the 3' UTR confirmed this, and indicated that the 3' end of the 3' UTR (nt 2285-2410) is required to influence expression in cervical-carcinoma cells. Further excessive expression of syndecan-1 suppressed growth in cervical-carcinoma cells. These results demonstrate that the reduction of syndecan-1 mRNA involved with the 3' untranslated region gives growth advantage to cervical-carcinoma cells.

Amino Acid Sequence↗
PubMed1999

Malignant transformation of human diploid fibroblasts and suppression of their anchorage independence by introduction of chromosome 13.

Isolation of cell lines that display various degrees of transformed phenotypes may be very useful to clarify multistep mechanisms of oncogenesis, but malignant transformation of human diploid fibroblasts in culture is a very rare event. We attempted to isolate variously transformed cell lines from human diploid fibroblasts (RB) of a patient with hereditary retinoblastoma. The RB cells exhibited normal karyotypes with the exception of one copy of chromosome 13, which contained a large deletion at the q14-22 region, where the RB1 gene is located. By transfection with SV40 early genes and repeated passage, we succeeded in obtaining SV40-transfected mortal, immortalized, anchorage-independent, and tumorigenic RB cell lines. DNA fingerprinting showed that these cell lines were not contaminants, but derivatives of the original RB cells. The remaining RB1 allele may be wild-type even in the malignant cell lines, because the expression and the LT-binding ability were normal. Furthermore, we did not find any homozygous loss in 16 polymorphic markers located in the 13q14-22 region in the transformed cell lines. However, introduction of a copy of a normal chromosome 13 into the anchorage-independent cell line suppressed its anchorage-independent growth ability. All these data, together with the fact that the RB cells containing the deletion progressed to a tumorigenic state spontaneously, but normal fibroblasts did not, raise the possibility that a new tumor suppressor gene, located at 13q14-22, may play a critical role in neoplastic transformation. We conclude that these RB cell lines provide an excellent system for identification of genes involved in malignant transformation of human cells. Genes Chromosomes Cancer 26:47-53, 1999.

Cell Adhesion↗
PubMed1999

Protection by a cyclic AMP-specific phosphodiesterase inhibitor, rolipram, and dibutyryl cyclic AMP against Propionibacterium acnes and lipopolysaccharide-induced mouse hepatitis.

OBJECTIVE AND DESIGN: To study the effect of cellular cAMP-increasing agents on Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS)-induced mouse hepatitis. MATERIAL: Male BALB/c mice were used. Macrophages/Kupffer cells isolated from P. acnes-primed murine liver were used for the in vitro study. TREATMENT: Type IV phosphodiesterase (PDE)-specific inhibitor, rolipram, was administered (10, 30 mg/kg, p. o.). Dibutyryl cyclic AMP (dbcAMP) was injected (10, 100 mg/kg, i.p.) into the mice. METHOD: Plasma TNFalpha estimated by the use of an L-929 cell cytotoxic assay and plasma transaminase activities were measured for the in vivo study. The LPS-induced production of TNFalpha in vitro from the cultured macrophage/Kupffer cells was determined by ELISA. RESULTS: Rolipram suppressed the elevation of plasma transaminases induced by injection of LPS, and dbcAMP had a tendency to suppress them. Both agents attenuated the LPS-induced release of TNFalpha in vivo, and suppressed the TNFalpha production from the cultured macrophage/Kupffer cells. CONCLUSIONS: These results suggest that rolipram and dbcAMP have potential to inhibit TNFalpha production from activated macrophage/Kupffer cells, and it may be partially involved in the protecting effect in the P. acnes/LPS hepatitis model.

Animals↗
PubMed1999

Mouse very low-density lipoprotein receptor (VLDLR): gene structure, tissue-specific expression and dietary and developmental regulation.

The very low density lipoprotein receptor (VLDLR) is a multifunctional apolipoprotein (apo) E receptor that shares a common structural feature as well as some ligand specificity to apo E with members of the low density lipoprotein receptor gene family. We have isolated and characterized the mouse VLDLR gene. The mouse VLDLR gene contains 19 exons spanning approximately 50 kb. The exon-intron organization of the gene is completely conserved between mouse and human. Since the 5'-flanking region of the mouse VLDLR gene contains two copies of a sterol regulatory element-1 like sequence (SRE-1), we next studied regulation of the VLDLR mRNA expression in heart, skeletal muscle and adipose tissue in C57BL/6, LDLR-/-, apo E-/- and LDLR-/-apo E-/- mice fed normal chow or atherogenic diet. The VLDLR mRNA expression was down-regulated 3-fold by feeding atherogenic diet in heart and skeletal muscle only in LDLR-/- mice. In contrast, VLDLR mRNA expression was up-regulated by atherogenic diet in adipose tissue in all animal models except double knockout mice. These results suggest that SRE-1 may be functional and VLDLR plays a role in cholesterol homeostasis in heart and skeletal muscle when LDLR is absent and that apo E is required for this modulation. Developmental regulation of the VLDLR mRNA expression was also tissue-specific. VLDLR mRNA expression in heart displayed significant up and down regulation during development. Maximal level was detected on post-natal day 3. However, the VLDLR mRNA levels in skeletal muscle remained relatively constant except a slight dip on post-natal day 7. In kidney and brain, VLDLR mRNA also peaked on post-natal day 3 but remained relatively constant thereafter. In liver, VLDLR mRNA expression was very low; it was barely detectable at day 19 of gestation and was decreased further thereafter. In adipose tissue, the VLDLR mRNA level showed an increase on post-natal day 13, went down again during weaning and then continued to increase afterwards. This developmental pattern as well as dietary regulation in adipose tissue supports the notion that VLDLR plays a role in lipid accumulation in this tissue. Although the primary role of VLDLR in heart, muscle and adipose tissue is likely in lipid metabolism, developmental pattern of this receptor in other tissues suggests that VLDLR has functions that are unrelated to lipid metabolism.

Adipose Tissue↗
PubMed1999

Pelvic malignant mixed mesodermal tumor of uncertain origin: a case report.

Extra-uterine, and especially extragenital, malignant mixed mesodermal tumors (MMMT) are very rare. A large intrapelvic tumor resected from a 56-year-old woman was investigated with morphological and immunohistochemical methods. A large, soft and fragile tumor was located in the pelvic space. The tumor showed high cellularity and was biphasic; it consisted of an admixture of adenocarcinoma and various kinds of sarcomas. The latter were comprised of high-grade endometrial stromal sarcoma, pleomorphic sarcoma, and chondrosarcoma. The pleomorphic sarcoma showed a storiform pattern. The periodic acid-Schiff-positive eosinophilic hyaline droplets and globules in multinucleated giant cells revealed a typical ring-like or peripheral staining for alpha-1-antitrypsin and alpha-1 antichymotrypsin. We considered this case to be pelvic MMMT of uncertain origin, heterologous type.

Combined Modality Therapy↗
PubMed1999

Lymphocyte-sensitivity to glucocorticoid correlates with the sensitivity to cyclosporin A and tacrolimus in chronic renal failure patients.

AIMS: Association between lymphocyte-sensitivity to immunosuppressants in transplant recipients in vitro and clinical outcomes has been demonstrated. In general, renal transplant recipients are treated with a combination of immunosuppressants such as either glucocorticoid/cyclosporin A (CsA) or glucocorticoid/tacrolimus (FK506) but the pharmacological complementarity of these drugs is still controversial. We examined relationships between the lymphocyte-sensitivities to these immunosuppressants. METHODS: We examined lymphocyte-sensitivities to prednisolone (PSL), CsA, and FK506 in vitro in a total of 190 chronic renal failure (CRF) patients and 140 healthy subjects. The lymphocyte-sensitivity was evaluated from the IC50 value against mitogen-stimulated lymphocyte-blastogenesis in vitro. RESULTS: Statistically significant correlations of the IC50 values in CRF patients between the following pairs of drugs were observed: PSL and CsA (P<0.0001; n=129, r=0.419), PSL and FK506 (P<0.001; n=54, r=0. 441), and CsA and FK506 (P<0.0001; n=45, r=0.608). Similar correlations were also observed in lymphocytes from healthy subjects. The population of CRF patients who exhibited high IC50 values (low sensitivities) to PSL and FK506 was significantly larger than that of healthy subjects (P<0.05). CONCLUSIONS: Patients who showed low lymphocyte-sensitivity to either of the drugs also may exhibit low sensitivity to the others, and thus they may have a high risk of unsatisfactory outcome under combination therapy after renal transplantation. To overcome this risk, the selection of immunosuppressants is recommended to be restricted according to individual lymphocyte-sensitivities to these drugs in vitro, or alternatively, by addition of other drugs with different mechanisms for immunosuppression.

Adult↗
PubMed1999

Myeloid differentiation antigen and cytokine receptor expression on acute myelocytic leukaemia cells with t(16;21)(p11;q22): frequent expression of CD56 and interleukin-2 receptor alpha chain.

We report the cellular characteristics of cells from three patients with de novo acute myelocytic leukaemia (AML) with t(16;21)(p11;q22), two M4 and one M5a according to the FAB classification, and two permanent cell lines with t(16;21)(p11;q22), TSU1621MT and YNH-1. The FUS/ERG fusion mRNA was demonstrated in all cases by reverse transcriptase-polymerase chain reaction (RT-PCR). The immunophenotypes of the AML cells, and YNH-1 and TSU1621MT cell lines with t(16;21) were characterized as CD34+CD33+CD13+CD11b+CD18+CD56+ HLA-DR-/+. Cells from all samples strongly expressed c-kit, granulocyte colony-stimulating factor receptor (G-CSFR), c-fms (macrophage colony-stimulating factor receptor), interleukin-3 receptor alpha chain (IL-3Ralpha), and granulocyte macrophage colony-stimulating factor receptor alpha chain (GM-CSFRalpha), and these data corresponded well to the growth responsiveness to the cytokines. IL-2Ralpha expression was also found in all t(16;21) samples, but IL-2 did not act on the proliferation of the leukaemic cells in in vitro cultures. G-CSF distinctly promoted the proliferation of leukaemic cells of t(16;21) AML, but did not enhance the expression of MPO and neutrophil differentiation of these cells. Our findings indicate that AML cells with t(16;21) preserve stem cell properties such as CD34 and c-kit expression, and suggest that they have the potential to differentiate into a monocytic lineage. The relationship between the unique cellular characteristics (especially CD56 and IL-2Ralpha expression) and FUS/ERG protein remains undetermined.

Adolescent↗
PubMed1999

De novo CD5-positive diffuse large B-cell lymphoma: clinical characteristics and therapeutic outcome.

To determine the clinical significance of CD5 expression in diffuse large B-cell lymphoma (DLBL) without a clinical history of low-grade B-cell lymphoma, we have reviewed the clinical features and therapeutic outcome of 25 patients with de novo CD5-positive DLBL, and compared the results with those of 87 patients with CD5-negative DLBL and 22 patients with mantle cell lymphoma (MCL). The patients with de novo CD5-positive DLBL had clinical characteristics of elderly onset (median age 63, range 37-91), and female predominance (male/female 10/15). 21 (84%) of these patients had extranodal involvement at presentation, with great variation in the sites. In comparison with the patients with CD5-negative DLBL, the treatment outcome for the patients with de novo CD5-positive DLBL was very poor with frequent relapse. The failure-free survival curve was almost identical to that of patients with MCL, showing that standard chemotherapy for DLBL was not effective for most of the patients with de novo CD5-positive DLBL. These findings suggest that de novo CD5-positive DLBL forms a distinct subgroup of DLBL.

Adult↗
PubMed1999

Multicenter study on the effects of day care therapy on schizophrenia: a comparison of day care patients with outpatients.

The effects of day care therapy for a period of 6 months upon patients with schizophrenia were studied through comparison with schizophrenia outpatients at four facilities in Japan. The clinical features of the 31 day care patients and 30 outpatients were evaluated by the hospital staff using the Positive and Negative Syndrome Scale (PANSS) and Global Assessment Scale (GAS), and by the patients' close relatives using the Katz Adjustment Scale (KAS) before and after 6 months of treatment. Day care patients showed a significant decrease in the general pathological score of PANSS and GAS, but outpatients did not show any comparable improvement. As for KAS scores, similar improvement was observed for both the day care patients and outpatients After 6 months, 43% of the day care patients improved on the post-/pre- PANSS total scores ratio, as against only 13% of the outpatients. In addition, 13% of the outpatients were readmitted due to an exacerbation of their symptoms, whereas all day care patients were able to remain at home for 6 months. This study clearly demonstrated that day care therapy for patients with schizophrenia was more effective than the usual outpatients treatment setting. Further therapeutic efforts (e.g. psycho-education) in day care therapy are needed in order to improve family member's evaluation of the patient.

Adult↗
PubMed1999

Experience with an ultrasonic aspirator in neuroendoscopy.

This report describes the clinical application of an ultrasonic aspirator for endoscopic neurosurgery. Eight patients with intraventricular hematoma with complete tamponade of the ventricular system and marked hydrocephalus were treated with the ultrasonic aspirator for endoscopic neurosurgery. Clinical evaluation and neuroimaging studies were obtained for one month. Removal of hematoma was confirmed on follow-up imaging. The ultrasonic aspirator is operated by electrostriction transducer on low generating power (15-30 watts). Its tube has an outer diameter of 1.8 mm. This aspirator is designed to fragment and aspirate the cattle-liver. On observing the adjacent neural and vascular structures with the neuroendoscope, the massive hematoma within the ventricles is removed with the use of this aspirator. Subtotal removal (> 90% of hematoma volume) was achieved in all patients. All patients tolerated the procedure well. However, postoperative re-rupture occurred in two patients prior to aneurysm clipping following an immediate interval. Three patients with hypertension, two patients with head trauma, and one patient after aneurysm clipping were discharged home within one month after treatment. Preliminary experience with this aspirator has demonstrated its feasibility and safety. Clinical application of this technique is expected in other fields of neurosurgery.

Adult↗