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Biomedical subjects

N Mitsuhashi

Publications and source records attributed to N Mitsuhashi.

At least 109 records · Page 6Linked to original sources

Prostaglandin biosynthesis in the umbilical artery and its relation to fetal growth.

Arachidonic acid metabolites were investigated in umbilical arteries of 16 normal pregnancies. Several prostaglandins (PGs) and hydroxyacids were synthesized by the umbilical artery. Prostaglandin I2, PGF2 alpha, PGE2 and PGD2 were found in the products, and PGI2 was the most abundant metabolite in the umbilical artery. The conversion rate of PGI2 from arachidonic acid is strongly correlated with the body weight of the baby (correlation coefficient: 0.621) and with the weight of the placenta (correlation coefficient: 0.668). PGI2 is known to be a strong vasodilator and anticoagulant, and is known to increase blood circulation. We therefore conclude that the PGI2-synthetic activity of the umbilical artery is strongly related to feto-placental blood flow and hence to fetal growth.

Adult↗

Prognostic factors of poorly-differentiated squamous cell carcinoma of the nasopharynx.

Retrospective analysis was performed with intent to evaluate prognostic factors in radiation therapy for 72 patients with histologically confirmed poorly-differentiated squamous cell carcinoma of the nasopharynx. The 10-year overall actuarial and cause specific survival rates were 36 and 40%, respectively. The median survival time was 43 months. Sixteen patients survived for more than 10 years (maximum 297 months). The five- and 10-year cause specific survival rates for Stages I, II, III and IV disease were 100 and 100%, 80 and 27%, 83 and 83%, and 38 and 31%, respectively. Two patients with Stage II disease died of a re-recurrent tumor more than seven years after their initial treatment. There was a significant difference between the survival curve for Stage I or III disease and that for Stage IV disease (P < 0.05). The patients with a T1-3 tumor had a statistically better survival rate than those with a T4 tumor (T1:T4, P < 0.001, T2 or T3:T4, P < 0.05). The patients with N0 had statistically better survival rates than those with N3 (P < 0.01). Twenty-eight patients developed loco-regional recurrence. Twenty-one patients developed distant bone metastases, most of which occurred within a year of the initiation of radiation therapy. The survival for the patients with loco-regional recurrence was nearly the same as that for the patients without loco-regional recurrence. The 10-year survival rates for patients with and without distant bone metastases were 0 and 48%, respectively (P < 0.001). Multivariate analysis revealed that the parameters influencing cause specific survival were stage categories of T and N, and adjuvant chemotherapy, whereas those influencing loco-regional recurrence were only stage categories of T and N. The only parameter to influence distant bone metastases was sex. We concluded the most important cause of failure for the patients with poorly-differentiated squamous cell carcinoma of the nasopharynx to be distant bone metastases.

Adolescent↗

Clinical study of radioprotective effects of amifostine (YM-08310, WR-2721) on long-term outcome for patients with cervical cancer.

PURPOSE: A retrospective analysis was performed to investigate the radioprotective effects of amifostine on the long-term outcome of radiation therapy for the patients with carcinoma of the uterine cervix. METHODS AND MATERIALS: Eighty-three patients with histologically proven epidermoid carcinoma (Stage II-IVA disease) of the uterine cervix were treated with definitive radiation therapy between January 1978 and December 1984. Forty-six patients treated with radiation alone, whereas 37 patients treated with radiation plus amifostine. Amifostine was given intravenously 30 min prior to every radiation. Most patients received 75 mg/m2 of amifostine daily from the initiation of the course of radiation therapy. The median total dose of amifostine given was 1300 mg/m2, with a range of 280 mg/m2 to 3700 mg/m2. RESULTS: The 5-year overall actuarial survival for the patients treated with radiation alone and with radiation plus amifostine were: 72% and 88% in Stage II disease (p = 0.45); 52% and 50% in Stage III disease (p = 0.68); and 40% and 43% in Stage IVA disease (p = 0.51), respectively. The 5-year intra-pelvic recurrence rates in the patients treated with amifostine were almost the same as those observed in the patients treated without amifostine (0% vs. 6% in Stage II disease; 15% vs. 10% in Stage III disease; 25% vs. 40% in Stage IVA disease). There was also no statistically significant difference of the chronic rectal or bladder complication rate between the groups treated by each regimen. CONCLUSION: We concluded that any radioprotective effects of amifostine on tumor tissue and any beneficial effects of amifostine against chronic radiation injury were not observed in the patients with cervical cancer followed up for more than 5 years after radiation therapy.

Amifostine↗

Radioimmunodetection of lung cancer with IMACIS-1, I-131 labeled monoclonal antibodies to CEA and CA19-9. Comparison of accumulations in irradiated and non-irradiated site.

IMACIS-1 is a radiopharmaceutical containing a mixture of Iodine-131 labeled monoclonal antibodies to CEA and CA19-9. IMACIS-1 immunoscintigraphy was evaluated for tumor detection in 7 primary lung cancer and 2 metastatic lung cancer patients who received radiotherapy. No adverse side effects due to IMACIS-1 were observed in this study. Positive detection was achieved in 5 of 9 patients (55.6%). It was less, but nearly the same as the detection rate obtained with Gallium-67 citrate (67Ga-citrate) in these patients. There was no clear correlation between IMACIS-1 accumulation and the CEA or CA19-9 serum levels. The IMACIS-1 positive detection rate decreased in many of the irradiated lesions. We considered that the decreased number of tumor cells and changes in blood perfusion are some of the factors controlling accumulation in tumors.

Adenocarcinoma↗

Second lung cancer following radiation therapy of locally advanced pulmonary cancer.

Three cases of second primary lung cancer following radiation therapy to the first pulmonary cancer were reported. In all cases, the first cancers located in the upper lobe and were unresectable diseases, their histologic type being epidermoid carcinoma. Radiation therapy was given with total doses of 60-70 Gy. Ten years later the second cancers arose in the contralateral lung and were treated with radiation therapy again.

Adenocarcinoma↗

Establishment and characterization of a rat yolk sac tumor cell line, NMT-1, producing alpha-fetoprotein, with potential for lymphatic metastasis.

A new cell line producing alpha-fetoprotein, designated NMT-1, was established from rat yolk sac tumor with the potential for lymphatic metastasis in inbred Wistar rats. In this paper, we investigated the characteristics of NMT-1 cells. The cell line grew in a monolayer and had a polygonal epithelioid appearance in phase-contrast microscopy. The doubling time of NMT-1 cells during exponential growth was approximately 16 h in RPMI-1640 with 10% fetal calf serum. The D0 value for radiation sensitivity was 97 +/- 3 cGy. The extrapolation number, n, for NMT-1 was 1.08 +/- 0.15. In the log phase, the G0/G1, S and G2/M fractions were 23.2%, 62.1% and 14.3%, respectively. Tumor take was observed in all of the rats inoculated with NMT-1 cells. In the case of flank tumor, the mean survival time was 104 days after inoculation with 10(6) tumor cells. Inguinal, axillary, paraaortic, mesenteric and mediastinal lymphnode metastases were observed in all rats inoculated with NMT-1 cells. Rats which survived for a long time developed metastases in a lymphatic vessels of the liver, lung and/or kidney microscopically. The biological behavior and the histopathological features of the tumor induced by inoculation with NMT-1 cells were the same as those of the original tumor induced by fetectomy.

Animals↗

Short communication: adverse chronic effects of high-dose irradiation on proximal bronchus in patients treated for bronchogenic carcinoma.

Of five patients with epidermoid carcinoma of the lung who were treated with small fields of 80 Gy in 40 fractions/8-11 weeks (TDF123-129) to the hilar region, four patients developed marked stenosis of the proximal bronchi without tumour progression and died of pulmonary insufficiency 1-3 years after radiotherapy. These results should serve as a warning against escalation of the radiation dose, and the upper optimal dose might prove to be less than 80 Gy for the treatment of pulmonary hilar lesions.

Aged↗

[Split-course radiation therapy in non-small cell lung cancer].

Split-course radiation therapy (Sp-RT) is based on theoretical differences between the kinetics of normal and malignant cells. A rest interval halfway through the course of treatment permits the normal tissues to recover, while the tumor shows vary little repopulation. Indeed, it shows mostly regression, resulting in shrinkage of the radiation field. From 1976 through 1985, 185 patients with localized but inoperable or unresectable (stage I-III) non-small cell carcinoma of the lung completed high-dose definitive RT delivered by continuous-course or split-course irradiation. Forty-seven patients who had large tumors or atelectases of the lung showing slow radioresponsiveness received Sp-RT over 60 Gy at 2 Gy per fraction. Rest periods were two or three weeks long in the interrupted schedules. The 5-year survival rate was 16% in the Sp-RT group and 13% in the continuous RT group. In the 33 patients that had differentiated epidermoid carcinoma with slow responsiveness to irradiation, the radiation fields could be shrunk by Sp-RT to the same extent as in the continuous group. Sp-RT was considered to be useful in the treatment of well-differentiated epidermoid carcinoma of the lung.

Adenocarcinoma↗

Palliative radiotherapy of bone metastasis.

We analyzed the effects of radiotherapy on 226 sites of metastatic bone tumors from 1981 to 1984, and on 157 sites of bone metastases of prostate cancer from 1970 to 1988. The radiation effect on pain relief was recognized in about 90% of cases within the dose of 20Gy to 30Gy, and there were not many differences in these effects according to the original tumors or histological types. In prostate cancer, the sites which needed re-irradiation were not recognized within 6 months after irradiation, and only 12 out of 80 sites (15%) that could be observed after more than 6 months needed re-irradiation due to recurring pain. As more than 60% of the patients with prostate cancer who needed irradiation to control bone metastases died within a year, to get pain relief by irradiation immediately and safely was thought to be very useful from the viewpoint of useful life. One patient was irradiated on 16 sites and 2 of these 16 sites received 4 treatments of irradiation and the shortest interval was 10 months and the longest one was 18 months.

Bone Neoplasms↗

In vivo effect of pituitary adenylate cyclase activating polypeptide 38 (PACAP 38) on the secretion of luteinizing hormone (LH) in male rats.

In view of the recent demonstrations that pituitary adenylate cyclase activating polypeptide (PACAP) 38 stimulates the release of LH from superfused pituitary cells and that the hypothalamus and anterior pituitary have highly selective binding sites for the peptide, we have surveyed the effect of intraatrial injections of PACAP 38 and vasoactive intestinal peptide (VIP), which has 68% homology with PACAP 38, in intact adult male rats. Furthermore the effect of intracerebroventricular (icv) injection of PACAP 38 was investigated. Intraatrial (10, 30, 100 micrograms) and icv (8, 32 micrograms) administration of PACAP 38 stimulated LH release significantly (P less than 0.01) in a dose-related fashion. Icv injection at a dose of 0.8 microgram was ineffective. The time course pattern of LH release by intraatrial injection and that by icv injection was similar, but the LH levels increased by intraatrial injection were much higher than that by icv injection. Intraatrial administration of VIP had almost no effect on LH release. These findings suggested that PACAP 38 stimulates LH release in vivo.

Animals↗

Endothelin-1 and endothelin-3 stimulate prostaglandin E2 secretion from the rat median eminence.

The in vitro effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) on the release of prostaglandin (PG)E2 from the rat median eminence were investigated. The addition of ET-1 from 10(-9) M to 10(-6) M stimulated PGE2 release in a dose-dependent manner (from 10.5 +/- 2.1 to 54.4 +/- 5.6 pg/ME fragment/30 min; mean +/- SEM, p less than 0.001). ET-3 also stimulated the release of PGE2 from 10(-7) M to 10(-5) M dose dependently (from 18.1 +/- 0.7 to 60.9 +/- 17.4 pg/ME fragment/30 min p less than 0.05). The time course effect of ET-3 (10(-6) M) showed that PGE2 release was stimulated within five minutes (control, 1.5 +/- 0.5; ET-3, 15.8 +/- 3.0 pg/ME fragment/5 min, p less than 0.01). These results suggest that ET-1 and ET-3 have some physiological effects on the rat median eminence.

Animals↗

[The concentration of endothelin in maternal vein, umbilical vein and artery of normal pregnancy and pregnancy-induced hypertension].

The concentrations of endothelin (ET) in maternal vein (MV), umbilical vein (UV) and artery (UA) of normal pregnancy (N) and severe pregnancy-induced hypertension (sPIH) were measured to investigate the significance of ET in the maternal and feto-placental circulation of normal pregnancy and PIH. 1) The concentrations of ET (pg/ml blood: mean +/- S.E.M.) in MV of a normal non-pregnant group, 1st, 2nd and 3rd trimester of N were 1.00 +/- 0.19 (n = 2), 0.55 +/- 0.16 (n = 4), 0.45 +/- 0.14 (n = 4) and 0.89 +/- 0.09 (n = 10), respectively. The concentration of ET in MV of 3rd trimester of sPIH was 2.76 +/- 1.21 (n = 7), and significantly (p less than 0.05) higher than in MV of 3rd trimester of N. 2) The concentrations of ET in UV and UA of N and UV of sPIH were 1.53 +/- 0.05, 1.29 +/- 0.06, 2.12 +/- 0.46, respectively. The concentrations of ET in UV and UA of N were significantly (p less than 0.01) higher than in MV of N. 3) The concentrations of ET in MV of N and sPIH correlated significantly (p less than 0.05) with diastolic blood pressure of N (r = 0.53). It was concluded that the synthesis of ET during pregnancy was suppressed until the 2nd trimester, and that the increased ET in MV of sPIH might be one of the factors that caused the pathogenesis of PIH. And the high concentration of ET in UV and UA was supposed to operate play a role in feto-placental circulation.

Adult↗

[Significance of the PGI2 producing enzyme system in the pathogenesis of pregnancy-induced hypertension].

Characterization of the PGI2 producing enzyme system (P.E.S.) in pregnancy induced hypertension (PIH) was carried out by comparing its conversion from arachidonic acid (A.A.) or PGH2 to PGI2 using enzyme preparations from endothelial cells of the umbilical vein in normal pregnancy (N) and mild (M) and severe (S) types of PIH. 1) The conversion rate from A.A. to PGI2 in N was significantly (p less than 0.05) higher than in M and S. 2) The conversion rate from PGH2 to PGI2 in N was higher than in M and that in M was higher than in S. 3) The apparent Vmax values (nM/mg protein) (mean +/- S.E.M.) for P.E.S. in N (0.88 +/- 0.21) were significantly (p less than 0.05) lower than in M (2.76 +/- 0.71) and S (1.63 +/- 0.18). The apparent Km values (microM) (mean +/- S.E.M.) for P.E.S. in N (0.76 +/- 0.25) were significantly (p less than 0.05) higher than in M (0.29 +/- 0.07) and significantly (p less than 0.05) lower than in S (3.26 +/- 0.78). 4) The apparent Vmax values for PGI2 synthetase (P.S.) in N (0.44 +/- 0.09) and M (0.61 +/- 0.10) were significantly (p less than 0.05) higher than in S (0.11 +/- 0.06). The apparent Km values for P.S. in N, M and S were 0.12 +/- 0.07, 0.13 +/- 0.06 and 0.16 +/- 0.04, respectively. The present study showed that the symptoms in M may be kept from becoming aggravated by the production of large amounts of PGI2, due mainly to activation of cyclooxygenase, whereas progressive disorder of the regulation of blood pressure in S may be caused by low production of PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Clinical evaluation of immunoscintigraphy with 131I anti-CEA and 131I anti-CA 19-9 monoclonal antibody cocktail (IMACIS-1)--report of the phase II study].

The clinical trials of immunoscintigraphy with a cocktail of 131I anti CEA monoclonal antibody F(ab')2 and 131I anti CA 19-9 monoclonal antibody F(ab')2 (IMACIS-1) were performed to evaluate the safety and clinical usefulness. Thirty-five patients with proven cancer in six hospitals were examined in the phase two study. No significant changes of the heart rates, temperature, blood pressure, respiratory rates and clinical laboratory data were observed after i.v. IMACIS-1. Significant elevation of HAMA and IgE values in serum were not shown. Positive scintigrams which were interpreted by each hospital were obtained in 31/35 (89%) patients and in 39/53 (74%) lesions. The safety and clinical usefulness of immunoscintigraphy with IMACIS-1 were proven in the phase two study.

Adult↗

[What is cure of the tumor with radiation therapy? Clinical viewpoint].

Tumors as malignant as lung cancer can be cured by radiation therapy. Local control is the primary requirement for complete cure of the tumor, but the continued presence of the mass demonstrated by imaging techniques does not necessary mean persistence of viable tumor cells. The mass shadow persisting in the region irradiated at a cure dose may simply represent delayed absorption of dead cells so that the patient should be observed for at least 3 months after the therapy. This requires patience on the part of clinitians, but erroneous additional irradiation must be avoided, because excess irradiation can do harm but no good. Radiosensitivity, radioresponsiveness, and radiocurability are all independent characteristics of the tumor. In general, the effects of radiation therapy must be evaluated comprehensively in consideration of these three characteristics of the tumor. Understanding of the natural history of the disease is essential for the treatment of malignant tumors. Therapeutic approach cannot be determined if the natural history of tumor is disregarded.

Aged↗

[Interactions of radiation and biological response modifiers (BRMs) in the treatment of malignant tumor].

This article reports on attempt to characterize the interactions of radiation and BRMs in the treatment of malignant tumor on the basis of our some experimental results. BRMs have a high possibility to enhance radiation effects on tumor cells with in a radiation field and bring some benefits to host tumor immune system with minimizing deleterious effects of irradiation to the immune responses. But it is very difficult to determine the rational design of administration of BRMs to induce the most effective interactions on relevant immune system and other host responses in the combination with radiotherapy. We should make it clear how radiation can be useful to potentiate the tumor antigenecity or antitumor immune responses.

Animals↗