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Biomedical subjects

T Ohigashi

Publications and source records attributed to T Ohigashi.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Retinoic acid-induced cell growth inhibition and differentiation in testicular carcinoma cells in culture].

Testicular germ tumor cells could be differentiated spontaneously or by some chemotherapeutic compounds. However, the mechanism by which the cells are differentiating from the stem cell remains unclear. The KU-MT cells, which were newly established from lung metastasis of testicular carcinoma, have been continuously producing alpha fetoprotein (AFP). Retinoic acids are well-known to induce cellular differentiation in culture and have already been applied for a clinical usage against leukemia. In the present study, all-trans-retionic acid (ATRA) elevated the level of AFP and inhibited the growth of KU-MT cells in vitro. ATRA also arrested the cell cycle in G1 and reduced the percentage of the S phase cell in terms of wild type p53, leading to apoptosis in part. Retinoids, especially retinoic acid receptor (RAR)-alpha specific agonists induced laminin production, a marker of endodermal differentiation; whereas arotinoid, a retinoid not bound to RAR-alpha, did not affect laminin expression. In summary, retinoic acids could mediate cell growth and differentiation of testicular tumor through RAR-alpha.

Antineoplastic Agents↗
PubMed1996

Autocrine regulation of erythropoietin gene expression in human hepatocellular carcinoma cells.

We have previously reported that a marked increase in erythropoietin (Epo) production can be demonstrated in Hep3B cell cultures in response to hypoxia (1). In order to determine whether this increase involves an autocrine mechanism, we have investigated the effects of purified human recombinant Epo (rHuEpo) on Epo production. Purified rHuEpo (5-80 mU/ml) produced a significant increase above control levels of Epo in Hep3B cell cultures under normoxic (20% O2) conditions. Hypoxic (1% o2) incubation of Hep3B cells with rHuEpo caused an increase over control levels of EpomRNA. Hep3B cells also expressed Epo receptor (Epo-R) transcripts. Binding studies [125I]Epo revealed that Hep3B cells contain a single class of binding site (kd=2.9 nmol/L and Bmax=1760 sites/cell). Antierythropoietin receptor monoclonal antibody inhibited the rHuEpo induced elevation in medium levels of Epo and blocked [125I]-Epo binding to Hep3B cell membranes. These results demonstrate that the expression of EpomRNA may be controlled, at least in part, by an autocrine mechanism.

Aerobiosis↗
PubMed1995

[Use of semirigid ureteroscopes for treatment of ureteral calculi].

BACKGROUND: The objective of this study is to evaluate the efficacy of ureteroscopic lithotripsy as the treatment of ureteral stones in the recent era by comparing the result using a semirigid ureteroscope with the result using a conventional ureteroscope. METHODS: Between 1991 and 1994, 136 patients with ureteral calculi underwent transurethral ureteroscopic lithotripsy in our hospital. From July 1991 to March 1993, 14F rigid ureteroscope with the rod lens system was used for 82 patients (group 1), whereas from April 1993 to July 1994 either a 9.5F or 7F semirigid fiberoptic ureteroscope was used for 54 patients (group 2). Insertion of ureteroscopes was performed under continuous irrigation of saline without mechanical dilation of the ureteral orifice in both groups. RESULTS: The rates of complete removal of stone at the first trial were 56.1% in group 1 and 72.2% in group 2 with the overall complete removal rate of 62.5%. The complete removal rates of stones in the upper, middle and lower ureters were 18.2%, 54.8% and 72.4% in group 1 and 14.3%, 72.7% and 88.0% in group 2, respectively. The major reasons for unsuccessful treatments was upward migration of stones during the procedure. As intraoperative complications, ureteral disruption occurred in 1 case in group 1, and ureteral perforation in 5 patients in group 1 (6.1%) and 2 in group 2 (3.8%). Acute bacterial infection with prolonged fever was observed in 3 patients in group 1 and in none in group 2. CONCLUSION: From these results, the new semirigid ureteroscope with fiberoptic imaging bundles made the transurethral lithotripsy a safer and more efficient procedure for the treatment of ureteral calculi especially those in the lower ureters.

Adolescent↗
PubMed1995

Enhancement of erythropoietin production by selective adenosine A2 receptor agonists in response to hypoxia.

The purpose of this study was to characterize the effects of two new adenosine A2 agonists, 2-(p-(2-carboxyethyl)phenethyl amino)-5'-N-ethylcarboxamidoadenosine (CGS-21680) and N6-(2(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl)-adenosine (DPMA), on erythropoietin (EPO) production in vivo and in vitro. Intravenous injections of CGS-21680 (100 to 500 nmol/kg mouse/day) and DPMA (50 to 500 nmol/kg mouse/day) for 4 days produced significant increases in serum levels of EPO in exhypoxic polycythemic mice. CGS-21680 (10(-7) to 10(-6) mol/L) and DPMA (10(-8) to 10(-5) mol/L) also produced significant increases in medium levels of EPO in a cloned EPO-producing Hep3B hepatocellular carcinoma cell line after 18 hours of incubation in 1% O2. Both compounds also increased cellular cAMP levels significantly in a dose-dependent manner after 1 hour of incubation. A2 receptor binding assays with tritiated CGS-21680 revealed a single type of adenosine receptor binding site on Hep3B cell membranes with a dissociation constant of 132.9 nmol/L and a binding capacity of 270.6 fmol/mg protein. The Ki competition binding values versus tritiated CGS-21680 were 217 nmol/L for CGS-21680 and 86.8 nmol/L for DPMA. These results indicate that adenosine A2 receptor activation amplifies EPO production in response to hypoxia, both in vivo and in vitro.

Adenosine↗
PubMed1994

Adenosine A2 receptor modulation of erythropoietin secretion in hepatocellular carcinoma cells.

The present studies were undertaken using a cloned erythropoietin (Ep) producing hepatocellular carcinoma cell line (Hep3B) to attempt to correlate the receptor binding properties and biological activities of 5'-N-ethylcarboxamideadenosine (NECA), N6-cyclohexyladenosine (CHA) and N6-cyclopentyldenosine (CPA). Ep and cAMP levels in cultures of Hep3B cells in response to these adenosine analogues were measured by radioimmunoassay. Receptor binding affinities of the adenosine analogues were determined by measuring inhibition of binding of [3H] NECA to Hep3B cell membranes. Scatchard analysis of [3H]NECA to Hep3B cell membranes. Scatchard analysis of [3H]NECA binding to Hep3B cell membranes indicates a single class of binding sites with a dissociation constant of 431 nM and a binding capacity of 573 fmol/mg protein. The adenosine analogues tested produced a significant increase in Ep secretion and cAMP accumulation (ED50 for cAMP accumulation, NECA = 3.3 x 10(-7) M, CHA = 4.2 x 10(-6) M, CPA = 2.2 x 10(-6) M). In addition, NECA showed a higher binding affinity (Ki, 3.8 x 10(-7) M) for Hep3B cell membranes in comparison with CHA (Ki, 6.3 x 10(-6) M) and CPA (Ki, 3.9 x 10(-6) M). These results indicate that the rank order for potency for NECA, CHA and CPA in their binding to Hep3B cell membrane receptors correlates very well with their biological effects on Ep secretion and cAMP accumulation in Hep3B cells.

Adenosine↗
PubMed1993

Effects of 5'-N-ethylcarboxamideadenosine (NECA) on erythropoietin production.

The present studies were undertaken to assess the effects of 5'-N-ethylcarboxamideadenosine (NECA), an adenosine analogue, on erythropoietin (Epo) production. NECA (0.05 and 0.1 mumol/kg i.v.) produced significant increases in serum Epo levels (368.8 +/- 56.1 and 384.6 +/- 45.9 mU/ml, respectively) in exhypoxic polycythemic mice after a four hour exposure to hypoxia when compared with hypoxia controls (133.2 +/- 18.2 mU/ml). The hypoxic kidney Epo levels were 46.4 +/- 13.4 mU/kg kidney which were significantly higher than normoxic kidney Ep levels (< 1.24 mU/kg kidney). Theophylline (20 mg/kg i.p.), an adenosine receptor antagonist, significantly inhibited the stimulatory effects of NECA on serum Epo levels. In vitro cultures of an Epo producing hepatocellular carcinoma (Hep3B) cell line with NECA (> or = 10(-6) M) for 20 hours under hypoxic conditions (1% O2) produced significant increases in medium levels of Epo when compared with hypoxia controls. Hepatocellular carcinoma cells treated with NECA at a concentration range of 10(-7) M to 5 x 10(-5) M for one hour in a hypoxic atmosphere also had significantly higher cAMP levels than that of hypoxia controls. Scatchard analyses of [3H]NECA binding to membrane preparations of hepatocellular carcinoma cells showed low affinity binding sites with a dissociation-constant (Kd) of 0.44 microM and a binding capacity of 863 fmol/mg protein. These findings suggest that the increase in Epo production in response to NECA under hypoxic conditions can be attributed, at least in part, to stimulation of adenosine A2 receptors which is coupled to adenylyl cyclase activation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

Adenosine A1 receptors and erythropoietin production.

N6-cyclopentyladenosine (CPA), a selective adenosine A1 receptor agonist, in a concentration range of 10(-9) to 10(-7) M, produced a significant decrease in erythropoietin (EPO) levels in a human hepatocellular carcinoma (Hep G2) cell culture (medium levels of EPO, 91.81 +/- 1.61 and 94.36 +/- 0.97% of control, respectively) after 24 h incubation in a hypoxic atmosphere. CPA, at a concentration of 10(-9) M, also produced a significant decrease in Hep G2 cell levels of adenosine 3',5'-cyclic monophosphate (cAMP; 78.13 +/- 3.89% of control) after 2 h incubation. CPA (10(-9) M) also significantly inhibited forskolin-stimulated increases in EPO production and cAMP accumulation in Hep G2 cells. On the other hand, 2-[p-(2-carboxyethyl)phenethyl-amino]-5'-N-ethylcarboxamidoadenosine (CGS-21680), a selective adenosine A2-receptor agonist, produced no significant change in EPO production in a dose range of 10(-10) to 10(-6) M but increased cAMP accumulation at 10(-6) M. A1-receptor binding assays using N6-[3H]cyclohexyladenosine revealed a single type of adenosine receptor binding site on Hep G2 cell membranes with a dissociation constant of 71.4 nM and a binding capacity of 1,530 fmol/mg protein. These results indicate that Hep G2 cells contain high-affinity adenosine A1 receptors that are linked to decreased cAMP accumulation and EPO production.

Adenosine↗
PubMed1993

Interaction of nitric oxide and cyclic guanosine 3',5'-monophosphate in erythropoietin production.

The present study was designed to investigate whether in vivo and in vitro erythropoietin (EPO) production is modulated by nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP). Serum levels of EPO in ex-hypoxic polycythemic mice were significantly increased after injections of 200 micrograms/kg sodium nitroprusside for 4 d. One injection of NG-nitro-L-arginine methyl ester (L-NAME) produced a significant dose-related decrease in serum levels of EPO in ex-hypoxic polycythemic mice in response to hypoxia. When EPO producing Hep3B cells were incubated in 1% O2 for 30 min, cGMP levels in the Hep3B cells were significantly elevated, compared with cells incubated in 20% O2. The elevation of cGMP by hypoxia was inhibited by L-NAME (100 microM). Sodium nitroprusside (10 and 100 microM) and NO (2 microM) also significantly increased cGMP levels in Hep3B cells. L-NAME, LY 83583 (6-Anilino-5,8-quinolinedione, a soluble guanylate cyclase inhibitor), and Rp-8-Bromo-cGMPS (Rp-8-Bromo-guanosine 3',5'-cyclic monophosphothioate, a cGMP-dependent protein kinase inhibitor) significantly inhibited the hypoxia-induced increase in medium levels of EPO in Hep3B cells. 8-Bromo-cGMPS produced a dose-dependent decrease in EPO messenger RNA levels in Hep3B cells in response to hypoxia. 8-Bromo-cGMP (10(-3) M) produced significant increases in medium levels of EPO in Hep3B cell cultures incubated under normoxic conditions, which was enhanced by the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (0.2 mM). These results suggest that NO and cGMP may interact in modulating hypoxic stimulation of EPO production.

Animals↗
PubMed1993

In vivo and in vitro erythropoietin activities in cultures of a hepatocellular carcinoma cell line.

The present studies were undertaken to characterize erythropoietin (Ep) production in an Ep-producing hepatocellular carcinoma (Hep3B) cell line. Hep3B cells which had been maintained in culture were transplanted under the renal capsule and subcutaneously in nude mice. The Hep3B xenograft doubling time is approximately 7 days. The mean hematocrit value of the Hep3B tumor-bearing nude mice was 33.2 +/- 1.1% (n = 8), which was significantly lower than that of control nongrafted nude mice (40.8 +/- 1.7%, n = 5). The Hep3B tumor-bearing nude mice showed significantly higher Ep levels in the sera (37.5 +/- 5.5 munits/ml, n = 8) than control nude mice (13.5 +/- 2.7 munits/ml, n = 5). Ep levels in the sera were correlated (R = 0.714) with the total Ep in the tumor extracts, whereas no Ep was detectable in any of the kidney extracts. On the other hand, an inverse linear relationship (R = -0.811) between the hematocrit values and Ep levels in the sera was demonstrated in the Hep3B tumor-bearing nude mice. The Hep3B cells recultured after growing in the nude mice were capable of enhancing Ep production in response to hypoxia, very similar to the original Hep3B cells which had been maintained in culture during the same time period. In addition, 15-methyl-prostaglandin E1 at a concentration range of 4-400 ng/ml produced significant increases in Ep secretion and cAMP accumulation in Hep3B cultures under hypoxic conditions (1% O2). The Ep produced by Hep3B cells expressed 3.7 times higher in vitro bioactivity than immunoactivity. The bioactivity of Hep3B Ep was completely neutralized by an antibody to highly purified human recombinant Ep. In contrast, the in vivo bioactivity of the Hep3B Ep was less than one tenth of its immunoactivity. These results indicate that the Hep3B tumor-bearing nude mice and the in vitro Hep3B culture system may provide a reproducible model system which should be useful for studies of the mechanism of Ep production.

Animals↗
PubMed1992

Bladder cancer cells express functional receptors for granulocyte-colony stimulating factor.

The effects of human recombinant granulocyte-colony stimulating factor (G-CSF) on the growth of cultured human bladder cancer cells and G-CSF receptor on these cells were investigated. Human bladder cancer cell lines, KU-1 or NBT-2, were incubated with and without G-CSF. At 48 hours, 3H-thymidine uptake of both cells was significantly higher with G-CSF (one ng./ml., 10 ng./ml.) than that of control without G-CSF (p less than 0.05). The binding of 125I-labeled KW-2228, a muteins of G-CSF, to KU-1 and NBT-2 was inhibited by unlabeled KW-2228 in a dose-dependent manner. These results demonstrated that G-CSF stimulates the clonal growth of human bladder cancer cells by binding to its specific receptors.

Carcinoma, Transitional Cell↗
PubMed1991

[Transurethral microwave thermotherapy of benign prostatic hypertrophy].

Transurethral microwave thermotherapy using Prostatron was performed in 31 patients with benign prostatic hypertrophy, and the clinical effectiveness was evaluated by analyzing the subjective and objective responses following the treatment. The 22F balloon catheter to be placed in the prostatic urethra incorporates the microwave antenna, a cooling system and a fiberoptic thermosensor which allow an effective delivery of microwave energy to the center of the prostate, while preserving the mucosa and periurethral tissue. The maximum urethral temperature during the treatment ranged from 43.3 to 45.5 degrees C (44.7 +/- 0.96 degrees C: mean +/- S.D.) and the average power output was 27.4 Watt. The treatment was performed in a single session of an hour on the outpatient basis. In one patient who could not be relieved of the indwelling catheter underwent a transurethral resection, and the histological effect of thermotherapy on the resected specimen was examined. In the prostatic tissue, heat-induced necrotic change of the interstitial tissue as well as degenerative change of the acinar epithelium were remarkable, whereas the urethral mucosa was well preserved. In the remaining 30 patients, the clinical effects were evaluated 8 weeks after the treatment by a score scale for subjective symptoms, residual urine and maximum urinary flow rate, which was compared with the pretreatment score. Improvement of both subjective symptoms and objective findings was observed in 13 subjects (43.3%), that of subjective symptoms only in 14 cases, and that of objective findings only in 2 cases, resulting in a notable improvement in total 29 cases (97.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

[Clinicopathological studies and flow cytometric analysis on renal cell carcinoma after incidental finding].

Of 173 patients with renal cell carcinoma treated at the Keio University Hospital between 1979 and 1989, 48 cases were found to have their tumors incidentally (group 1), and the remaining patients presented with signs and/or symptoms related to their tumors (group 2). In this study we attempted to define the clinicopathological and ploidy characteristics of the tumors in the patients of the two groups. The number of patients having tumor stages not exceeding pT2NOMOV- was significantly higher in group 1 (81.3%) than in group 2 (36.0%) (p less than 0.001), and the median tumor size was significantly smaller in group 1 (4.32 +/- 2.38 cm) than in group 2 (7.86 +/- 4.07 cm) (p less than 0.001). The survival rate in group 1 was significantly favorable when compared with group 2 (p less than 0.005). And even in the same stage (pT1-2NOMOV-) there were statistical significance in the survival and relapse rate between the two groups (p less than 0.05), which indicate that renal cell carcinomas detected incidentally are associated with biologically low malignant potential. From 1985, flow cytometric DNA analysis was performed in 32 tumors from the group 1 and in 50 from the group 2. The frequency of occurrence of aneuploid pattern was significantly lower in tumors from the group 1 (25.0% in the overall patients and 16.0% in those with stage pT1-2NOMOV- tumors of group 1) than in those from the group 2 (52.0% in the overall patients and 42.9% in those with stage pT1-2NOMOV- tumors) (p less than 0.05). These results also suggest that renal cell carcinomas detected incidentally are associated with low malignant potential biologically.

Adult↗
PubMed1990

Endourologic management of filling defect in renal pelvis: limited value of cold cup biopsy.

A fifty-six-year-old woman underwent transurethral ureterorenoscopy and cold cup biopsy for evaluation of a filling defect of the left renal pelvis. The pathology indicated a benign lesion, and percutaneous resection was done with the nephroresectoscope. However, the pathologic diagnosis of the resected tissue showed it to be transitional cell carcinoma, grade I. Consequently we performed a nephroureterectomy with excision of a cuff of bladder and the nephrostomy tract. Residual tumor was found in deep layer of the renal pelvis. The implication from this case in defining the indications for endourologic management of tumors is considered.

Biopsy↗
PubMed1990

Granulocyte-colony stimulating factor enhances the cytotoxic effects of methotrexate to bladder cancer cells in vitro.

It is possible that a strategy designed to stimulate cancer cells in the active cell cycle may increase the effectiveness of S-phase specific anti-cancer agents such as methotrexate. In this study, the effects of granulocyte-colony stimulating factor (G-CSF) on the proliferation of cultured human bladder cancer cells and on the cytotoxicity of anti-cancer drugs to bladder cancer cells were studied in vitro. The 3H-thymidine uptake of cultured human bladder cancer cells, KU-1 and NBT-2, was significantly higher when the cells were treated with 10 ng/ml G-CSF than without G-CSF after 24- and 48-hour incubation. However, the cell numbers of KU-1 and NBT-2 were not significantly affected by 72-hour treatment with 10 ng/ml G-CSF. The binding of 125I-labeled KW-2228, a muteins of G-CSF, to KU-1 and NBT-2 was inhibited by unlabeled KW-2228 in a concentration dependent manner, which demonstrated the presence of G-CSF receptors on both cells. Scatchard analysis showed that the receptor densities of KU-1 and NBT-2 were 1770 and 3070 per cell, respectively. The combination treatment with methotrexate and G-CSF resulted in a significant increase in cytotoxic effects, when compared with methotrexate treatment alone. This study supports the possibility that the combination therapy of methotrexate and G-CSF increases clinical response in the treatment of advanced bladder cancer.

Cell Cycle↗
PubMed1990

[Percutaneous removal of renal and upper ureteral stones: clinical results and complications of 103 cases].

We report the results and complications of 103 consecutive patients who underwent percutaneous removal of renal and ureteral stones. The overall clinical success rate was 80.6%. For the recent 33 cases in which UL-arm fluoroscopy was used, however, the success rate was as high as 87.9%, which was considered to be due to easier establishment of percutaneous direct access. The most common complications were bleeding (18.5%), extravasation (15.5%) and fever (9.7%). Four cases with significant bleeding required arteriography, but there were no sign of arteriovenous fistula nor pseudoaneurysms in any cases. To study renal parenchymal damage in the percutaneous procedures, plasma renin activities (PRA) were compared in 54 cases after six months. However, significant elevation of PRA did not occur in any case.

Adult↗
PubMed1990

[Atresia hymenalis with acute urinary retention: a case report].

We report a case of atresia hymenalis in a 14-year-old girl presenting with a clinical symptom of acute urinary retention. On physical examination she was found to have a lower abdominal mass and an imperforate bulging hymen. She underwent hymenal incision, and subsequently the symptom disappeared. It is very uncommon for atresia hymenalis to manifest itself with acute urinary retention as the first clinical sign, but we should consider this disease if a pubertal girl seeks medical opinion for acute urinary retention.

Acute Disease↗