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Biomedical subjects

K Ohmi

Publications and source records attributed to K Ohmi.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Experimental study on direct toxicity of combined cisplatin and methotrexate for normal and neoplastic cell lines].

The combination effect of cisplatin (CDDP) and methotrexate (MTX) on the cytotoxicity against normal fibroblast and malignant cell line were investigated utilizing MTT assay. In case of normal fibroblast, the optical density (OD) value in CDDP + MTX was significantly higher and remained at a consistently higher value in various mixture rates than that in CDDP alone. Such low cytotoxicity may be due to MTX because the addition of Leucovorin resulted in an apparent decrease in the OD value. The combination of the two drugs was thought to alleviate the toxicity of CDDP on fibroblast, in contrast to its increase on cancer cells.

Animals↗
PubMed1998

Human microvascular endothelial cells are strongly sensitive to Shiga toxins.

We show here that the susceptibility of endothelial cells to Shiga toxin (Stx)s differs remarkably depending on their cellular origins. The concentration of Stx-1 required to reduce cell viability by 50% as measured by MTT assay was 30 and 300 fM for neonatal and adult human microvascular endothelial cells (HMVEC), respectively, and 30 pM for human coronary artery endothelial cells (HCAEC). Human umbilical venous endothelial cells (HUVEC) and bovine aortic endothelial cells (BAEC) showed no sensitivities to Stx-1. Surprisingly, Stx-2 was approximately 10-100 times more toxic to HMVEC than Stx-1. Moreover sodium butyrate sensitized HMVEC by 100-fold to the cytotoxic activity of Stxs. These results were found to reflect the amount of Gb3/CD77 on the cell surface on a per cell basis using flow cytometrical analysis. The high sensitivity of HMVEC to Stxs suggests their involvement in the pathogenesis of organ failure induced by Stx-producing Escherichia coli.

Adult↗
PubMed1998

Intracellular aggregate formation of dentatorubral-pallidoluysian atrophy (DRPLA) protein with the extended polyglutamine.

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder caused by the abnormal CAG triplet-repeat expansion resulting in an elongated polyglutamine (polyQ) stretch. We have recently showed that the DRPLA protein is cleaved during apoptosis by caspase-3, one of the cysteine protease family members known to be activated during apoptosis. We report here the subcellular localization of the DRPLA protein by fusing the green fluorescent protein as a tag. The full length DRPLA protein is localized predominantly but not exclusively in the nucleus regardless of the length of the polyQ stretch. In contrast, an N-terminal-deleted fragment containing polyQ produced by the proteolytic cleavage with caspase-3 is found both in the nucleus and the cytoplasm. Moreover, the same fragment with the elongated polyQ showed aggregation when overexpressed. Some cells with aggregate formation showed apoptotic phenotype. These findings raise the possibility that the DRPLA protein processed by caspase-3 may lead to aggregation of the protein resulting in the development of neurodegeneration.

Apoptosis↗
PubMed1998

Reconstruction for the brilliance-upgrading project of the Photon Factory storage ring.

Reconstruction of the Photon Factory storage ring (PF ring; 2.5 GeV) is now in progress to provide very brilliant synchrotron radiation to users, i.e. the emittance is being reduced by a factor of five. Components, such as the quadrupole and sextupole magnets, vacuum chambers, beamlines and beam-position monitors, are being replaced by new ones in 16 normal-cell sections of the PF ring. The accelerating cavities, injection systems and control systems are also being replaced. Operation will commence when the improvements are completed on 1 October 1997.

Journal Article↗
PubMed1998

Mitsugumin29, a novel synaptophysin family member from the triad junction in skeletal muscle.

In skeletal muscle, excitation-contraction (E-C) coupling requires the conversion of the depolarization signal of the invaginated surface membrane, namely the transverse (T-) tubule, to Ca2+ release from the sarcoplasmic reticulum (SR). Signal transduction occurs at the junctional complex between the T-tubule and SR, designated as the triad junction, which contains two components essential for E-C coupling, namely the dihydropyridine receptor as the T-tubular voltage sensor and the ryanodine receptor as the SR Ca2+-release channel. However, functional expression of the two receptors seemed to constitute neither the signal-transduction system nor the junction between the surface and intracellular membranes in cultured cells, suggesting that some as-yet-unidentified molecules participate in both the machinery. In addition, the molecular basis of the formation of the triad junction is totally unknown. It is therefore important to examine the components localized to the triad junction. Here we report the identification using monoclonal antibody and primary structure by cDNA cloning of mitsugumin29, a novel transmembrane protein from the triad junction in skeletal muscle. This protein is homologous in amino acid sequence and shares characteristic structural features with the members of the synaptophysin family. The subcellular distribution and protein structure suggest that mitsugumin29 is involved in communication between the T-tubular and junctional SR membranes.

Amino Acid Sequence↗
PubMed1998

Cerebral metastasis in patients with uterine cervical cancer.

We report on eight patients who developed brain metastases following uterine cervical cancer. The mean interval between diagnosis of the primary cancer and diagnosis of the brain metastasis was 28.4 months (range: 6.1-61.8 months). Nausea and vomiting due to increased intracranial pressure were the most frequent symptoms. Surgical excision of the brain lesions, followed by postoperative radiotherapy, was performed in three patients. The other five patients received only cranial radiotherapy. When the metastatic brain lesions were detected, other distant metastatic lesions were confirmed at the same time in five patients. The median survival time after diagnosis of the brain metastases was only 3.0 months.

Adenocarcinoma↗
PubMed1998

Clinicopathological factors predicting retroperitoneal lymph node metastasis and survival in endometrial cancer.

BACKGROUND: By clarifying the significance of clinicopathological factors for retroperitoneal lymph node metastasis and survival of patients with endometrial cancer, we suggest ideas for optimal treatment of this disease. METHODS: A retrospective study was conducted in 310 women with endometrial cancer who underwent surgery with retroperitoneal lymphadenectomy. To evaluate retroperitoneal lymph node metastasis, age-adjusted and multivariable analyses were carried out for six clinicopathological factors including pathological grade, myometrial invasion, cervical invasion, peritoneal cytology, lymphatic permeation and vascular invasion. To evaluate survival, besides the above factors, a positive rate of metastasis of dissected retroperitoneal lymph nodes was included. RESULTS: In 40 patients (13%) with nodal metastasis, the average positive rate of metastasis of dissected retroperitoneal lymph nodes was 22%. For retroperitoneal lymph node metastasis, the odds ratio of deep myometrial invasion, cervical invasion and severe lymphatic permeation were 5.97, 2.72 and 12.01, respectively. For survival, the hazard ratios of the positive rates of metastasis of dissected retroperitoneal lymph nodes (both 25% and < 25%), positive peritoneal cytology and poor pathological grade were 7.10, 3.24, 3.82 and 3.27, respectively, and 5-year survival rates for them were 0, 50, 72 and 77%, respectively. CONCLUSIONS: For retroperitoneal lymph node metastasis, lymphatic permeation, deep myometrial invasion and cervical invasion were the independent prognostic factors. For survival, retroperitoneal lymph metastasis, poor pathological grades and positive peritoneal cytology were the independent prognostic factors. The positive rate of metastasis of dissected retroperitoneal lymph metastasis plays an important role in predicting survival of endometrial cancer. Lymph node biopsy is insufficient in treatment of this disease.

Adenocarcinoma↗
PubMed1998

[Intraoperative local infusion chemotherapy (ILIC) for gastric cancer].

In order to provide a high dose of cis-diammine dichloro platinum (CDDP) into the regional lymph nodes and surrounding organs during operation, "intraoperative local infusion chemotherapy (ILIC)" was devised and has been applied to advanced gastric cancer patients. The aims of this method are 1) to reduce the possibility of metastasis by affecting the cancer cells before flowing out; 2) to administer drugs to the cancer cells which evade surgical resection; 3) to administer drugs to the lymphatic flow; and 4) to reduce the systemic side effects. After the laparotomy, the part of the stomach for gastrectomy was isolated from the blood supply, applying clamps to the proximal and distal parts of the stomach and hemostats to feeding blood vessels. Through a feeding artery to the tumor, 50 mg of CDDP was injected. Twenty-four patients underwent ILIC from June 1986 to December 1993. The 5-year survival rate was significantly better in the ILIC group compared to the control group which was selected by the matched pair method. The newly devised ILIC chemotherapy is a promising way to improve the prognosis of advanced gastric cancer patients. A randomized prospective study should be undertaken.

Animals↗
PubMed1997

A novel aortic smooth muscle cell line obtained from p53 knock out mice expresses several differentiation characteristics.

Here we report that we could obtain a highly differentiated smooth muscle cell line by screening the expression of a-smooth muscle actin from p53 knook out mice aorta. This cell revealed extended bipolar shape and expressed h-caldesmon and calponin as well as a-smooth muscle actin as protein markers of differentiated smooth muscle. Further intracellular calcium increase was induced by application of noradrenaline in a dose dependent manner and calcium oscillation was also observed in a higher dose (100 microM). Appropriate application of 5-azacytidine enhanced these tendencies and induced slow contraction by endothelin-1 and phenylephrine.

Animals↗
PubMed1995

High dose rate brachytherapy for carcinoma of the uterine cervix: comparison of two different fractionation regimens.

PURPOSE: There is no consensus as to the best dose-fractionation regimen in high dose rate (HDR) brachytherapy for cervix cancer. Since 1983, two fractionation regimens have been used in different time periods at National Cancer Center Hospital, and their treatment results have been compared in terms of 5-year survival, local control, and complication rate to find the better therapeutic regimen. METHODS AND MATERIALS: From November 1983 to October 1990, 130 patients with uterine cervix carcinoma were treated with HDR intracavitary brachytherapy using a remote afterloading system. There were 21 Stage Ib patients, 5 Stage IIa, 29 Stage IIb, 2 Stage IIIa, 68 Stage IIIb, and 5 Stage IVa. The median age was 64 years. The median follow-up time was 50 months. Radiotherapy consisted of external beam irradiation to the pelvis (mean dose of 50 Gy), combined with HDR brachytherapy (mean dose of 20 Gy to point A) given 5 Gy per session twice weekly (group A: 54 patients) or 6 Gy once weekly (group B: 76 patients). RESULTS: The overall 5-year survival was 52% in group A and 72% in group B. Local recurrence rate was 11%, and distant failure rate was 21%, with no difference between the two groups. The complication rate was significantly lower in group B (37%) than in group A (55%). Multivariate analysis has shown that factors affecting survival were stage, brachytherapy dose, and local control status. No factor was predictive of local control, but the external beam radiation dose significantly influenced the risk of complications. CONCLUSION: The once-weekly HDR intracavitary applications combined with properly adjusted external beam pelvic irradiation is a safe and effective treatment for patients with uterine cervix cancer.

Adenocarcinoma↗
PubMed1995

Frequent occurrence of c-Ki-ras gene mutations in well differentiated endometrial adenocarcinoma showing infiltrative local growth with fibrosing stromal response.

The frequency of c-Ki-ras mutation was examined by polymerase chain reaction (single-strand conformation polymorphism and direct sequencing analysis) and its association with histological parameters was analyzed in 110 endometrial adenocarcinoma hysterectomy specimens. The c-Ki-ras mutation was detected in 24 cases (22%). It occurred irrespective of tumor size, stage or histological grade, and was more frequent in tumors associated with endometrial hyperplasia (11 of 20, 55%) than in those without (10 of 73, 14%). In addition, the frequency of the mutation was significantly higher in tumors showing an infiltrative growth pattern accompanied by a stromal response consisting of edematous fibrous tissue (19 of 58, 33%), than in those which revealed an expansive growth pattern without such a stromal reaction (five of 52, 10%). Even among tumors showing the infiltrative growth pattern, the frequency of c-Ki-ras mutation was especially high (48%) in grade I cases in comparison with grade II or III cases (20% and 19%). Mutational activation of the c-Ki-ras gene may act at two points in the developmental pathway of endometrial adenocarcinoma by enhancing evolution of hyperplasia to adenocarcinoma, and by producing an infiltrative growth with a fibrosing stromal response.

Adenocarcinoma↗
PubMed1995

Prognostic value of p53 protein accumulation in cancer cell nuclei in adenocarcinoma of the uterine cervix.

Adenocarcinoma of the uterine cervix (CxAd) is one of the most distressing malignancies of the female reproductive system because of its tendency to spread aggressively and to be resistant to radiation and systemic therapies. To clarify the prognostic significance of p53 alteration in CxAd, we immunohistochemically examined the incidence of p53 nuclear accumulation, which is considered to be mostly parallel with p53 gene mutation, and its association with clinicopathological parameters in 26 patients with CxAd. The overall incidence of p53 nuclear accumulation was 46% (12 of 26), being higher in groups with clinically advanced disease, higher degrees of cellular atypia, and deeper myometrial invasion, but significantly lower in patients with integration of human papillomavirus (HPV) type 16 or 18 DNA. Nuclear p53 immunoreactivity as well as lymph node status, depth of invasion and the absence of HPV-DNA integration were significant indicators of a poor prognosis. Examination of p53 nuclear accumulation could be applied to biopsy material, and would be of practical assistance in predicting the prognosis of CxAd both preoperatively and postoperatively.

Adenocarcinoma↗
PubMed1993

K252a: a new blocker of the cell-cycle at G1 phase in a human hepatoma cell line.

The administration of 200 nM K252a to HuH7 suppressed the proliferation of the cells almost completely. The uptake of [3H]thymidine was inhibited, and flow cytometry revealed only one peak at 2C on day 3 after treatment with 100 nM K252a. The expression of proto-oncogene c-myc was not reduced. Despite the blockage at G1, both the size of the cells and the amount of cell protein had increased by 4 times by day 3 after treatment with K252a, while the cells secreted albumin and alpha-fetoprotein into the medium as usual. These results show that K252a can increase the cell size of HuH7 without losing its function by blocking the cell cycle at G1 phase.

Carbazoles↗
PubMed1993

Induction of giant endothelial cells in culture by K-252a, a protein kinase inhibitor.

K-252a, a protein kinase inhibitor with a wide spectrum of activity, inhibited the serum-stimulated proliferation of cultured bovine carotid endothelial cells dose-dependently, and all the cells became remarkably large, with a diameter of more than 150 microns at K-252a concentrations of 0.3-1 microgram/ml. This effect of the agent was reproducible under the conditions described in this article. When the endothelial cells became abnormally large by K-252a, the surface area of the cell became wider, and the F-actin molecules increased in both number and length. Despite their abnormal size, K-252a-induced giant cells maintained at least three physiological functions characteristic to normal endothelial cells: 1) ability to take up acetylated low density lipoprotein, 2) ability to produce and secrete endothelin and 3) ability to respond via an increase of [Ca2+]i to the stimulation by bradykinin. These observations suggest that K-252a-induced giant cells are useful tools for examining the function of endothelial cells because it is very reproducible and can be produced by an easy treatment.

Actins↗
PubMed1991

Analysis of the interaction of reserpine with actin by the photoaffinity labelling method.

The interaction of reserpine with one of the cytoskeletal proteins, actin, was analyzed by the photoaffinity labelling method using [3H]reserpine. Reserpine bound sufficiently to G- or oligomeric actin, but hardly to F-actin under the same experimental conditions. This result could be explained if reserpine binds to a specific region of the G-actin molecule that is responsible for actin-actin interactions. It is concordant with this idea that [3H]reserpine bound only to specific proteolytic fragments of actin. When reserpine was mixed with crude extracts of two kinds of tissues, chicken gizzard smooth muscle and bovine adrenal medulla, it bound to the 42 kDa protein of sodium dodecyl sulfate-polyacrylamide gel electrophoresis in both cases. Its molecular size and abundance suggest strongly that this 42 kDa protein is actin. The binding of reserpine to actin was inhibited by dopamine in a dose-dependent manner. These results suggest that actin could be one of the target molecules of reserpine.

Actins↗
PubMed1991

Gynandroblastoma of the ovary having a typical morphological appearance: a case study.

A rare gynandroblastoma of the right ovary with a typical morphological appearance in a 65-year-old woman is reported. The tumor comprised both a granulosa cell element with a Call-Exner body and a Sertoli cell element. Pathologically, this case could be the most typical of all the world's established cases. Clinically, there were feminizing symptoms such as post-menopausal genital bleeding and endometrial cystic hyperplasia. Pre-operative serum hormonal assays indicated elevated levels of estrone, estradiol and testosterone, and low levels of gonadotropins. These returned to normal after surgery.

Aged↗