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Biomedical subjects

T Ohno

Publications and source records attributed to T Ohno.

At least 145 records · Page 8Linked to original sources

High level of CA19-9, CA50, and CEA-producible human cholangiocarcinoma cell line changes in the secretion ratios in vitro or in vivo.

The ascites of a 78-yr-old Japanese woman with cholangiocarcinoma was used for a primary culture. An established new cell line (designated TK from the Japanese description of cholangiocarcinoma; Tankan-gann) showed conspicuous tumor marker production. A high level of circulating serum tumor markers; carbohydrate antigen (CA) 19-9, 32,000 U/ml; CA50, 6900 U/ml; and carcinoembryonic antigen (CEA), 300 ng/ml (on an average from 10(6) cells/ml for 3 d culture) were detected in the tissue culture supernatant. With an inoculum of 2 x 10(7) TK cells, nude mice progressively developed tumors. The histological features of the tumors forming in nude mice showed well-differentiated adenocarcinoma. Within the tumor mass, large amounts of extra cellular fluid retained approximately 590,000 U/ml of CA19-9, 200,000 U/ml of CA50, and 2000 ng/ml of CEA. Alpha-feto-protein was undetectable in the TK culture supernatant. There are few cholangiocarcinoma cell lines producing stable human tumor markers. Newly established TK cells derived from cholangiocarcinoma showed a stable production of serum tumor markers in vivo and in vitro. The changes in the tumor marker secretion ratios were shown to be dependent upon type of tumor cells, i.e., whether they are in vitro or in vivo. These features make TK cells a valuable tool for studying tumor markers.

Aged↗

Developing a new model for non-insulin dependent diabetes mellitus (NIDDM) by using the Philippine wild mouse, Mus musculus castaneus.

The Philippine wild-caught castaneus mouse (Mus musculus castaneus) and laboratory mouse (C57BL/6J: B6) were used to develop a new non-insulin dependent diabetes mellitus (NIDDM) model. Offspring from the cross between a wild male and B6 female were backcrossed to the sire. One male which exhibited highest fasting hyperglycemia (190 mg/dl) among eighty-seven backcross offspring was selected at 10 weeks of age, and crossed with a B6 female to comprise the fundamental stock (F0). Thereafter, full-sib mating was performed to develop a new inbred strain named CBD (Castaneus-B6 diabetic) mouse. Mice with relatively higher fasting hyperglycemia among F0 and F1 generations were selected for breeding. From the F2 generation, mice were defined as diabetic when blood glucose levels exceeded 200 mg/dl at 120 min in intraperitoneal glucose tolerance test (IPGTT) at 10 weeks of age, and have been selectively bred. The incidence of diabetic males from the F3-F6 generation fluctuated 45-75% at 10 weeks of age and 59-72% at 20 weeks of age. Diabetic males had about two-fold higher fasting glucose and insulin levels than B6 males. Glucose-stimulated insulin secretion was impaired in diabetic CBD mice compared to B6 males at 20 weeks. Moreover, diabetic mice had slight obesity compared to B6 mice. These facts indicated that diabetic features of CBD mice resemble NIDDM in humans. The CBD strain, characterized by high incidence and early onset of diabetes with mild obesity would be of value as a new NIDDM model. The method, utilizing wild castaneus mouse of different origin from laboratory mice, maybe useful in the development of other animal models.

Animals↗

Distribution of body weight, blood insulin and lipid levels in the SMXA recombinant inbred strains and the QTL analysis.

In the SMXA recombinant inbred (RI) strains, we measured body weight, blood insulin and lipid (triglyceride, total cholesterol and phospholipid) levels in each strain. In the five traits, mean values of substrains varied remarkably and showed a continuous spectrum of distribution, suggesting control by multiple genes at distinct loci for each trait. We also screened for quantitative trait loci (QTLs) involved in the five traits. Suggestive QTLs for body weight (Chromosomes 1 and 6), insulin (Chromosomes 1, 3, 10 and 17), triglyceride (Chromosomes 4 and 11) and phospholipid (Chromosome 18) levels were detected. The SMXA RI strains are unique tools for analyzing genetic factors that influence body weight, blood insulin and lipids levels.

Animals↗

Characterization of hyperinsulinemic recombinant inbred (RI) strains (SMXA-5 and SMXA-9) derived from normoinsulinemic SM/J and A/J mice.

We discovered two mouse strains (SMXA-5 and SMXA-9) with hyperinsulinemia among the substrains and progenitor strains (SM/J and A/J) of the SMXA recombinant inbred (RI) strains, and characterized the two strains at 20 weeks of age. SMXA-5 (mean +/- S.E.M: 9.6 +/- 1.7 ng/ml) and SMXA-9 (7.7 +/- 1.3 ng/ml) males had higher serum immunoreactive insulin levels than SM/J (1.4 +/- 0.3 ng/ml) and A/J (1.1 +/- 0.1 ng/ml) males in the nonfasting condition. The hypoglycemic response to insulin at 30 min after injection was significantly less in SMXA-5 males than in SM/J mice. Glucose tolerance test revealed that the incidence of impaired glucose tolerant males was 58% (11/19) in SMXA-5 and 42% (10/24) in SMXA-9 strains, but none in SM/J and A/J strains. SMXA-5 (209 +/- 29 mg/dl) and SMXA-9 (235 +/- 31 mg/dl) had higher serum triglyceride levels than SM/J (126 +/- 14 mg/dl) and A/J (89 +/- 5 mg/dl) males in the nonfasting condition. Histologic examination revealed enlarged islets in the pancreas of hyperinsulinemic SMXA-5 male mice. Moreover, SMXA-5 and SMXA-9 mice exhibited mild obesity. SMXA-5 and SMXA-9 males were therefore characterized by hyperinsulinemia, impaired glucose tolerance, hypertriglyceridemia and mild obesity which resembled some of the phenotypes of human Syndrome X, although both progenitor strains were normal so far as we examined. Since the RI strains are a powerful tool to facilitate polygenic-trait analysis, SMXA-5 and SMXA-9 mice will be useful materials to investigate the genetic basis of complex diseases, and are possible new metabolic models in relation to hyperinsulinemia.

Animals↗

Randomized comparison of mobilization kinetics of circulating CD34+ cells between biweekly CHOP and dose-escalated CHOP with the prophylactic use of lenograstim (glycosylated rHuG-CSF) in aggressive non-Hodgkin's lymphoma. The lenograstim/Lymphoma Study Group.

High-dose chemotherapy with autologous hematopoietic stem cell transplantation has been expected to result in a promising outcome in high risk aggressive non-Hodgkin's lymphoma (NHL). However, it remains unknown what type of initial chemotherapy is optimal, especially regarding progenitor cell mobilization. Sixty-three untreated patients with aggressive NHL in a high risk group were randomized to either a biweekly arm with 8 cycles of standard CHOP or 6 cycles of the dose-escalated CHOP arm with cyclophosphamide 1.5 g/m2 and doxorubicin 70 mg/m2. Lenograstim (glycosylated rHuG-CSF 2.0 microg/kg/day) was administered daily from day 3 to patients in both arms. The mobilization effect of the two regimens on circulating CD34+ cells was evaluated. Twenty-seven of 29 patients in the biweekly CHOP arm and 33 of 34 patients in the dose-escalated CHOP were assessable. Dose-escalated CHOP yielded a significantly higher number of circulating CD34+ cells in the first cycle compared with biweekly CHOP (p=0.05). The peak number of circulating CD34+ cells with biweekly CHOP did not significantly change from cycle to cycle; however, in dose-escalated CHOP, the peak number of circulating CD34+ cells mobilized after the fifth and sixth cycle was lower than after the first cycle (p=0.07 and 0.009, respectively). Routine conventional-dose chemotherapy and low-dose G-CSF can mobilize sufficient CD34+ cells in patients with aggressive NHL. The mobilization kinetics of circulating progenitor cells in patients with aggressive NHL is dependent on the dosage and schedule of CHOP.

Adjuvants, Immunologic↗

Lack of integrated TT virus (TTV) genomes in cellular DNA in infected human hematopoietic cells.

TT virus (TTV) isolated from the serum of a patient with posttransfusion hepatitis has been characterized as a member of the Circoviridae, a family of small DNA viruses with single-stranded circular genomes. TTV appeared to infect not only the serum and liver, but also the peripheral blood mononuclear cells (PBMC). We investigated the prevalence of TTV DNA in human hematopoietic cells, based on 84 mononuclear cell samples obtained from the bone marrow or lymph nodes of patients with hematopoietic malignancies including leukemia, malignant lymphoma and aplastic anemia. Forty-nine (58.3%) out of the 84 samples were positive for TTV DNA with polymerase chain reaction analysis, which was almost similar to the frequency found in the patients' serum. Southern blot analyses using a 3.2-kb fragment derived from the TTV DNA, however, showed no evidence supporting the fact that the TTV genomes are integrated into the human hematopoietic cell genomes, thus suggesting their existence as episomal forms.

Blotting, Southern↗

Enhanced radiation killing by 5-fluorouracil of biliary tract cancer cell lines.

Despite the frequent clinical use of 5-fluorouracil (5-FU) in combination with radiotherapy for patients with biliary tract cancers, data remain scarce concerning specifically the influence of 5-FU on the sensitivity of these cancer cells to radiation. The present study was carried out to evaluate the effects of concomitant treatment with 5-FU on radiation-induced cell killing in two established human biliary tract cancer cell lines (Mz-ChA-2 and SK-ChA-1 cells). These lines were chosen as we have previously shown that SK-ChA-1 cells are significantly more resistant to both radiation and 5-FU than Mz-ChA-2 cells. Clonogenic survival was employed as the end-point for cell killing. Administration of 5-FU at LD50 doses to each cell line significantly enhanced radiation-induced cell killing. The enhancement ratio (ER) was obtained by dividing the radiation dose required to decrease the cell survival fraction to 37% (D0) by the dose to decrease cell survival to the same level when the cells were also treated with 5-FU. The ER in each of the cell lines was greater when they were incubated with 5-FU after radiation rather than prior to radiation. Longer exposure times with 5-FU resulted in enhanced radiation killing. The ER was significantly higher in the radioresistant cell line than in the radiosensitive line. These findings suggest that therapy with radiation and 5-FU may be of value as components of multidisciplinary treatment for biliary tract cancer. Protracted low dose exposure to 5-FU may prove to be most efficacious in enhancing the effects of radiation therapy.

Biliary Tract Neoplasms↗

Influence of anteroposterior and mediolateral instability on range of motion after total knee arthroplasty: an ultrasonographic study.

Ultrasonographically, the femoral component and the tibial plate of total knee prostheses are strongly echogenic, while the high-density polyethylene insert is hypoechoic. This study evaluated the influence of mediolateral and anteroposterior stability after total knee arthroplasty (TKA) on range of motion using real-time monitoring with ultrasound. Mediolateral stress translation, which is increased by horizontal resection of more bone at the ends of the femur or tibia for easy prosthesis implantation, was examined on coronal scans at the level of the collateral ligaments. Anteroposterior drawer was examined on sagittal scans at the level of the patellar tendon. Mediolateral translation (0-10 mm; mean 2.24 mm) did not correlate with range of motion, while anteroposterior drawer (2-10 mm, mean 5.05 mm) correlated well with range of motion. These ultrasonographic findings suggest that horizontal over-resection of the ends of the femur and tibia contributed to joint laxity, which would not result in better ROM. Rollback and sliding of the femoral component on the tibia, which is believed to be correlated with anteroposterior drawer, may be important in achieving better range of motion and obtaining excellent results in TKA.

Hip Prosthesis↗

[Intravascular large B-cell lymphoma associated with hypoalbuminemia and hypoxemia].

A 67-year-old man was referred to our hospital for treatment of hemophagocytic syndrome. Hypotension, hypoxemia, pleural effusion, severe anasarca, and splenomegaly were noticed at the time of admission. Laboratory findings showed anemia (7.7 g/dl), thrombocytopenia (4.5 x 10(4)/microliter), an increase of serum LDH (1,466 IU/L) and severe hypoalbuminemia (1.9 g/dl). Bone marrow aspiration revealed an increase of reticulum cells with active hemophagocytosis and the presence of immature lymphocytes (6.0%). Lymphoma was suspected, but effective chemotherapy could not be performed because of progressive hypoxemia and severe hypoalbuminemia, and the patient died of the disease 2 weeks after admission. Autopsy revealed large lymphoid cells packed within systemic vessels as well as invasion into organs such as the liver, lungs, and spleen. The postmortem diagnosis was intravascular large B-cell lymphoma. Hypoalbuminemia and hypoxemia appear to be important clinical features of intravascular large B-cell lymphoma.

Aged↗

[C1q deficiency].

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Complement C1q↗

[C2 deficiency].

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Complement C2↗

[C4 deficiency].

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Complement C4↗

Induction of effective antitumor immunity in a mouse brain tumor model using B7-1 (CD80) and intercellular adhesive molecule 1 (ICAM-1; CD54) transfection and recombinant interleukin 12.

Although tumor-specific T lymphocytes recognize tumor-associated antigens (TAA) present on their cell surface via major histocompatibility complex (MHC) molecules, T cells require other activating signals. These are provided by costimulatory molecules, including B7-1 (CD80), B7-2 (CD86) and intercellular adhesive molecule 1 (ICAM-1; CD54). Transfecting mouse tumor cell lines with the B7 gene can lead to primary tumor rejection and the establishment of protective immunity. However, some studies have shown that the B7 effect upon T-cell-dependent tumor immunity is limited. Therefore, we examined the antitumor effects of recombinant interleukin 12 (IL-12) and genetically engineered glioma cells expressing B7-1 or both B7-1 and ICAM-1. Vaccination of mice with B7-1-expressing tumor cells substantially inhibited the growth of subcutaneously inoculated gliomas but not those located in the brain. Vaccination with B7-1-expressing tumor cells and systemic recombinant IL-12 (rIL-12) was more effective than either B7-1-expressing tumor cells or rIL-12 alone. Our murine brain tumor model also showed that vaccination with tumor cells expressing both B7-1 and ICAM-1 combined with rIL-12 prolonged survival. We have demonstrated the therapeutic potential of vaccination with rIL-12 and tumor cells expressing both B7-1 and ICAM-1 in the control of glioma growth.

Animals↗