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Biomedical subjects

T Chihara

Publications and source records attributed to T Chihara.

At least 19 recordsLinked to original sources

Characterization of a novel aquaretic agent, OPC-31260, as an orally effective, nonpeptide vasopressin V2 receptor antagonist.

1. OPC-31260, a benzazepine derivative, has been studied for its ability to antagonize the binding of arginine vasopressin (AVP) to receptors in rat liver (V1) and kidney (V2) plasma membranes, for antagonism of the antidiuretic action of AVP in alcohol-anaesthetized rats and for diuretic action in conscious normal rats. 2. OPC-31260 caused a competitive displacement of [3H]-AVP binding to both V1 and V2 receptors with IC50 values of 1.2 +/- 0.2 x 10(-6) M and 1.4 +/- 0.2 x 10(-8) M, respectively. 3. OPC-31260 at doses of 10 to 100 micrograms kg-1, i.v., inhibited the antidiuretic action of exogenously administered AVP in water-loaded, alcohol-anaesthetized rats in a dose-dependent manner. OPC-31260 did not exert an antidiuretic activity suggesting that it is not a partial V2 receptor agonist. 4. After oral administration at doses of 1 to 30 mg kg-1 in normal conscious rats, OPC-31260 dose-dependently increased urine flow and decreased urine osmolality. The diuretic action of OPC-31260 was characterized as aquaresis, the mode of diuretic action being different from previously known diuretic agents such as furosemide, hydrochlorothiazide and spironolactone. 5. The results indicate that OPC-31260 is a selective V2 receptor antagonist and behaves as an aquaretic agent. OPC-31260 will be a useful tool in studying the physiological role of AVP and in the treatment of various conditions characterized by water retention.

Administration, Oral

Interleukin-8 is a major neutrophil chemotactic factor derived from cultured human gingival fibroblasts stimulated with interleukin-1 beta or tumor necrosis factor alpha.

Inflammatory mediators produced by cells in the gingiva have been implicated in the initiation and progression of periodontal disease, a common infectious disease. In this study, we examined the biological activity of neutrophil chemotactic factors and the kinetics of expression of interleukin-8 (IL-8) mRNA derived from normal gingival fibroblasts in response to inflammatory mediators in an in vitro model. Gingival fibroblasts stimulated by either recombinant human interleukin-1 beta or recombinant human tumor necrosis factor alpha produced neutrophil chemotactic factors after 4 h, whereas expression of cell-derived IL-8 mRNA was detected within 1 h after stimulation. Furthermore, in a neutralization assay, rabbit anti-recombinant human IL-8 antiserum inhibited neutrophil chemotactic activity to basal levels. These results provide evidence that gingival fibroblasts synthesize potent chemotactic factors such as IL-8 in the presence of the inflammatory mediators interleukin-1 beta and tumor necrosis factor alpha. The activity of these factors may contribute to neutrophil-mediated processes in the pathogenesis of periodontal disease.

Cells, Cultured

OPC-21268, an orally effective, nonpeptide vasopressin V1 receptor antagonist.

An orally effective, nonpeptide, vasopressin V1 receptor antagonist, OPC-21268, has been identified. This compound selectively antagonized binding to the V1 subtype of the vasopressin receptor in a competitive manner. In vivo, the compound acted as a specific antagonist of arginine vasopressin (AVP)-induced vasoconstriction. After oral administration in conscious rats, the compound also antagonized pressor responses to AVP. OPC-21268 can be used to study the physiological role of AVP and may be therapeutically useful in the treatment of hypertension and congestive heart failure.

Administration, Oral

Possible involvement of pertussis toxin-sensitive GTP-binding protein(s) in c-fos expression during differentiation of 3T3-L1 fibroblasts to adipocytes.

Following the differentiation of 3T3-L1 fibroblasts by insulin/dexamethasone/methylisobutylxanthine, marked increases in cAMP levels by isoproterenol but not forskolin and in 2-deoxyglucose uptake by insulin occurred. Pertussis toxin-pretreatment prior to addition of insulin/dexamethasone/methylisobutylxanthine and exposure of cells to pertussis toxin during differentiation attenuated glycerophosphate dehydrogenase activity as a differentiation marker enzyme and the responses to isoproterenol and insulin by approximately 50% of those in pertussis toxin-untreated cells. On the other hand, insulin/dexamethasone/methylisobutylxanthine caused induction of c-fos proto-oncogene in confluent 3T3-L1 fibroblasts. This induction was also reduced in pertussis toxin-pretreated cells. These results suggested that pertussis toxin-sensitive GTP-binding protein(s) is involved in expression of c-fos mRNA accompanied by differentiation. In addition, accumulation of c-fos mRNA by insulin/dexamethasone/methylisobutylxanthine was enhanced in protein kinase C-depleted cells pretreated with phorbol 12-myristate 13-acetate, indicating that protein kinase C may negatively regulate c-fos expression induced by insulin/dexamethasone/methylisobutylxanthine.

1-Methyl-3-isobutylxanthine

[Intestinal T-cell lymphoma (so-called malignant histiocytosis of the intestine) complicated by multiple perforations].

We describe a case of intestinal T-cell lymphoma which was histologically diagnosed of malignant histiocytosis of the intestine. A 47-year-old man was admitted to our hospital because of fever and generalized lymphadenopathy. Mild anemia, leukocytosis, positive CRP and a high level of LDH were noted. Pathological finding of the lymph node was compatible with dermatopathic lymphadenopathy with a slight increase in atypical lymphoid cells. At the 14th day after admission, he suffered from abdominal pain and was diagnosed as having perforative peritonitis. In laparotomy, the infiltration of histiocyte-like atypical cells were found around a site of small perforation of the terminal ileum. The findings were compatible with that of malignant histiocytosis of the intestine (MHI). He had recurrent perforations of the small intestine and died of peritonitis and sepsis at the 42nd day. Southern blot analysis of the biopsied lymph node showed TCR-beta gene rearrangement. Some patients diagnosed clinically and pathologically as having MHI may have a T-cell lymphoma like our case.

Histiocytic Sarcoma

Clinical evaluation of sizofiran combined with irradiation in patients with cervical cancer. A randomized controlled study; a five-year survival rate.

Following a previous report we ascertained the effectiveness of sizofiran (Schizophyllan:SPG) to prolong the survival and time to recurrence of the patients with Stage II or III cervical cancer, as evaluated in a 5-year randomized controlled study conducted in 19 institutions in Japan. Of the overall patients with Stage II or III cancer, time to recurrence and survival rate in the group on SPG were significantly longer than in the control group. In the Stage II patients, there was significant difference in time to recurrence, and survival of SPG group tended to be longer than that of the control group. However, in the Stage III patients, there was no significant difference in either time to recurrence or survival rate.

Antineoplastic Agents

[Comprehensive clinical study on pathogenesis of early spontaneous abortion].

Clinical studies on the natural history of early spontaneous abortion included ultrasonic examination of the conceptus, determination of serum human chorionic gonadotropin beta (H), evaluation of trophoblast viability (V), chromosomal analysis of chorionic tissue and assessment of the mixed lymphocyte reaction-blocking effect (BE) of serum in 22 cases with missed abortion and 4 with incomplete abortion. TV was evaluated by simultaneous staining with fluorescein diacetate-propidium iodide (FDA-PI). The data obtained were as follows: 1) Chromosomal abnormalities were observed in 13 of 21 patients analyzed. 2) V was 78.6 +/- 5.6 (n = 7) in induced abortion, 42.3 +/- 16.2 (n = 22) in missed abortion and 8.8 +/- 4.8 (n = 4) in incomplete abortion. 3) There was a significant linear correlation between the maximum diameter of the gestational sac (D) and the weight of the chorionic tissue (W) (W = 1.30 + 0.08D, r = 0.44, p less than 0.05), and between the titer of H and the weight of the viable chorionic tissue (Wv = W x V) (Wv = 0.66 + 0.01H, r = 0.77, p less than 0.01). Consequently, the following formula was devised: V = (H + 66)/(0.08D + 1.30). 4) Results obtained from the formula indicated that V stays at an elevated level for some time and then falls gradually or rapidly after fetal death in spontaneous abortion. 5) Spontaneous expulsion of the conceptus occurred when V declined to about 10% in 4 cases. 6) There was a significant linear correlation between BE and V (V = 34.58 + 0.31BE, r = 0.45, p less than 0.05). It was thus concluded that the intrauterine retention period of the conceptus after fetal death is dependent on V, which can be estimated by D, H and BE in spontaneous abortion.

Abortion, Missed

Clinical evaluation of schizophyllan combined with irradiation in patients with cervical cancer. A randomized controlled study.

To evaluate the clinical effects of the anti-tumor polysaccharide Schizophyllan (SPG), a randomized study was done on 220 patients with Stage II or Stage III cervical cancer who had been given irradiation, concomitantly. The tumor-reducing effect of SPG was significant in patients in either stage. The time to recurrence was longer in SPG-dosed patients with Stage II cancer, compared with findings in the control group. There was no significant difference in the time to recurrence in patients with Stage III cancer between the SPG and control groups. When comparing the 48-month survival curve, the survival time of patients with Stage II cancer in the SPG group was significantly longer than in the control group. However, there was no significant difference in the survival rate of patients with Stage III cancer between the SPG-dosed and control groups.

Actuarial Analysis

The prognostic significance of the minimum thickness of uninvolved cervix in patients with cervical carcinoma stages IB, IIA, and IIB.

The minimum thicknesses of uninvolved cervical tissues at the sites of deepest tumor invasion were evaluated in 899 patients with Stage IB, IIA, and IIB cervical carcinoma. Minimum thicknesses were greater than or equal to 10 mm in 126 (14%), 5-10 mm in 247 (27%), and less than 5 mm in 335 (38%) patients. Parametrial extension was found in 191 (21%) patients. Nodal metastasis rates were 6, 10, 22, and 55%, respectively. Patients with greater than or equal to 10-mm thicknesses did not have two or more positive nodes (P less than 0.05). The proportion of patients with two or three positive nodes increased from 3 to 10% (P less than 0.005) as the minimum thickness decreased from 5-10 to less than 5mm. The proportion of patients with four or more positive nodes increased from 3 to 22% (P less than 0.001) in cases in which tumor invaded the parametrial tissues. Five-year disease-free rates were 99, 93, 88, and 65%, respectively. Each percentage decrease was significant (P less than 0.05, 0.05 less than P less than 0.01, and P less than 0.001). These results indicate that uninvolved cervical thickness is a good indicator of nodal metastases, number of positive nodes, and patient prognosis.

Carcinoma

Postoperative extended-field irradiation in patients with pelvic and/or common iliac node metastases from cervical carcinoma stages IB to IIB.

Radical hysterectomy with pelvic and common iliac lymphadenectomy was done for 207 Stage IB (148), IIA (19), and IIB (40) cervical carcinomas. Pelvic nodal involvement was limited in 30 (14.5%) cases, whereas common iliac nodes were involved in 16 (7.7%) cases. Common iliac node metastases were significantly increased, when the number of positive pelvic nodes increased from 2 to 3 or 4 or more (21.4% to 73.3%, P less than 0.05), when the tumor invaded deeper than 20 mm (3.7% to 22.2%, P less than 0.001), and when the tumor extended into parametrial tissues (4.8% to 14.8%, P less than 0.05). Postoperative extended-field irradiation was administered to 40 patients with nodal metastases. The 3-year disease-free rates were 85% in 24 patients with positive pelvic nodes, and 51% in 16 patients with common iliac node metastases; 70% in total. These results indicate that postoperative extended-field irradiation is essential for those patients with nodal metastases from locally resectable cervical carcinomas.

Adenocarcinoma

[Radiation-induced secondary cancer in patients with uterine carcinoma].

PURPOSE: Radiation-induced cancer has been epidemiologically investigated in occupational or atomic radiation exposure cases. These is also a need to clarify the risk in the case of radiotherapeutical exposure. In this study, therefore, cases of post-irradiated uterine carcinoma which was well cured and followed up over a long term were selected for statistical analysis of radiation-induced cancer in the medical division. MATERIALS AND METHODS: A total of 19,384 patients with uterine carcinoma at seven institutions in Japan were registered on a computer system at the NIRS and were statistically analyzed. Of these, 6,655 patients were treated by surgical procedure alone, 4,310 were given a combined treatment modality of radiation and surgery, 8,419 were treated by radiation alone between 1960 and 1978. Radiation-induced cancer was defined according to the following categories: Secondary cancer was developed within the irradiated field. Time interval was over 5 years after the initial irradiation (leukemia was over 2 years). The cancer had a different histological type to the original one. A total of 43 patients with induced cancer were observed, namely: 14 with rectal cancer, 8 with leukemia, 6 with uterine corpus cancer, 4 with urinary bladder cancer, 3 with osteosarcoma or uterine sarcoma, 2 with sigmoid colon cancer or malignant fibrous histiocytoma, and 1 with ovarian cancer, respectively. RESULTS: Rectal cancer, leukemia and urinary bladder cancer were initially analyzed, because their expected values were easily estimated from the basic data. A total of 8,333 patients (43,418 person-years) from 7 institutions were considered. Their average follow-up period was 10.2 years after treatment. 1) Rectal cancer: Observed value (O) = 14, expected value (E) = 7.83, O/E = 1.79, 95% confidence interval of O/E ratio (CI) = 0.98-2.99, there was no significant difference. 2) Leukemia: O = 8, E = 3.78, O/E = 2.12, CI = 0.91-4.18, no significant difference. 3) Urinary bladder cancer: O = 4, E = 2.23, O/E = 1.79, CI = 0.49-4.55, no significant difference. In other words, no significant difference was observed in the risk of occurrence of secondary cancer among the total number of irradiated patients from the 7 institutions. Since these results, however, were influenced by the accuracy of patient follow-up, the O/E ratio of double cancer in each institution was observed to check the accuracy of the follow-up and 3 institutions were selected for further analysis comprising 2,686 patients (13,588 person-years) in all. Their average follow-up period was 10.1 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged

Evaluation of CA125 as a circulating tumor marker for ovarian cancer.

CA125 usefulness was evaluated using sera from healthy persons, pregnant women, and patients with ovarian and other tumors. Since serum CA125 levels significantly depended on sex and age in healthy persons, the original cut-off levels were 40 and 25 U/ml in terms of sex and age. Changes in CA125 levels within 40 U/ml were observed during the menstruation cycle. Elevation of CA125 levels was also observed during the first trimester of pregnancy, but these levels fell below 50 U/ml as pregnancy progressed. Immunostaining of the endometrium with OC125 suggested that ovarian function may play an important role in production of CA125 in early pregnancy and menstruating young women. Elevated levels of CA125 were detected in 33/34 (97%) cases with surgically demonstrated ovarian cancer. The clinical usefulness of CA125 for monitoring the course of ovarian cancer was reconfirmed. Practical application of CA125 proved to be useful for the early detection of ovarian cancer and confirmation of the complete disappearance of any tumor.

Adult