Bestatin at mid to high concentration had inhibitory effect to [3H]thymidine incorporation of human lymphocytes. It also decreased the PHA-P, Con A and PWM-induced mitogenicity of human lymphocytes. On the contrary, bestatin had growth stimulatory effect to murine lymphocytes, and enhanced the Con A, LPS-induced mitogenicity of murine lymphocytes. These growth inhibitory (human) and stimulatory (mouse) effect of bestatin was found to be independent of adherent cells (macrophage and dendritic cell), indicatory directly working to T or B lymphocytes.

Aminopeptidases↗

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Treatment of Vogt-Koyanagi- Harada's disease during pregnancy.

BACKGROUND: Caution should be exercised in treating patients with autoimmune diseases during pregnancy. CASES: We successfully treated three cases of Vogt-Koyanagi-Harada's disease (VKH disease) during pregnancy. OBSERVATIONS: In the second trimester (14-27 weeks) of 1 patient, inflammation was mild and could be treated by topical corticosteroid. There is the possibility that her immune response had been modified by pregnancy. Systemic corticosteroid in a high dose was administered to the two cases in the second and third trimesters of pregnancy (28-41 weeks). The severity of inflammation in these 2 patients was similar to that in nonpregnant women. Inflammation subsided immediately without recurrence in all cases. No abnormality was found during the deliveries or in the babies. CONCLUSIONS: Treatment for VKH disease during pregnancy should be chosen according to the severity of inflammation, the stage of pregnancy, and the maternal and fetal conditions.

Adult↗

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Genome analysis of adenovirus type 4 strains isolated from acute conjunctivitis in Japan.

Strains of adenovirus type 4 (Ad4) isolated from patients with acute conjunctivitis were studied by DNA restriction analysis. The strains were isolated between July and December 1990 in Japan. All 63 isolates of Ad4 were identified as the genome type Ad4a. This study showed that the same Ad4 genome type, Ad4a, caused acute viral conjunctivitis, even in different areas of Japan.

Acute Disease↗

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Anisocytosis precedes onset of the large granular lymphocyte leukemia in aged F344/N rats.

In investigations using experimental animals, the unexpected affection of certain diseases often cause great impairment to them especially when using aged animals. In F344 rats, large granular lymphocyte leukemia is the most frequent fatal disease which increases along their aging. The timely detection of rats at risk for leukemia is very important in order to exclude such animals and thus obtain precise results in many fields of investigation. In the process of assessing the main cause of death in F344/N rats of the aging farm of our institute, NILS, we found cases with no obvious contributory disease to death that showed anisocytosis in a peripheral blood smear. In such cases, histological examination of spleen revealed consistent features of leukemia and findings of the liver and kidney were considered due to this hematologic disorder. Anisocytosis was frequently seen in the advances stage of leukemia. Thus we concluded that anisocytosis is a prior condition of leukemia and its detection in a peripheral blood smear is predictive of the disease when using aged animals.

Journal Article↗

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Age-dependent changes in noradrenergic innervations of the frontal cortex in F344 rats.

Noradrenergic innervations of the frontal cortex with advancing age (9, 13 and 25 months) in male F344 rats were quantified by immunohistochemistry for dopamine-beta-hydroxylase (DBH), which is a marker enzyme for noradrenergic axons. The density of DBH-positive axons, varicosities (swellings along an axon from which noradrenaline is released), and the number of varicosities per unit length of axon were measured in the frontal cortex. We found that the density of axons and varicosities significantly decreased at an earlier stage of aging (9-13 months), but not at a later stage (13-25 months). On the other hand, the number of varicosities per unit length of axon did not change with age. The result shows that the density of varicosities, which represent the synapses of noradrenergic neurons, decrease in the frontal cortex in the early aging process.

Aging↗

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Adjuvant pelvic irradiation in patients with pathologic T2b carcinoma of the uterine cervix.

Patients with cervical cancer are subject to postoperative adjuvant therapy if the histopathologic examination reveals parametrial involvement. This study evaluated the patterns of failure in patients with pathologic parametrial invasion (pT2b) treated with adjuvant pelvic irradiation. Between April 1985 and March 1997, 45 patients with pT2b cervical cancer were treated with postoperative pelvic irradiation. The median age was 52 years. Preoperative clinical stages were stage Ib in 8 patients, IIa in 4, and IIb in 33. Twenty-three patients had lymph node metastasis. The median total dose of whole pelvic radiation therapy was 50 Gy. Occurrence of pelvic failure or distant metastasis according to the nodal status was examined. None of the 22 patients without lymph node metastasis developed distant metastasis. Among the 23 node-positive patients, 6 developed distant metastasis as an initial failure site. The 5-year overall survival of the entire group was 78%. The actuarial distant metastasis-free rates at 5 years were 73% and 100% for those with and without pelvic lymph node metastasis, respectively (P = 0.016). Results support previous evidence for chemoradiation in patients with pelvic lymph node metastasis. However, it appears that the role of systemic chemotherapy for node-negative pT2b patients is yet to be established.

Adult↗

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Clinical role of Tc-99m-MIBI scintigraphy in non-Hodgkin's lymphoma.

This study was designed to investigate the relationship between Tc-99m-hexakis-2-methoxyisobutylisonitrile (MIBI) scintigraphy and outcome of treatment in patients with non-Hodgkin's lymphoma (NHL). Forty-five patients with NHL were studied with Tc-99m-MIBI before any treatment. Images of the lesions were obtained at 20 min and 2 h after radionuclide administration. Visual semi-quantitative interpretation was performed for Tc-99m-MIBI (grade 0-4) scintigraphy. Patients underwent 3-5 cycles of CHOP chemotherapy with/without involved field radiotherapy for large tumors. Their responses to treatment were evaluated at the end of chemotherapy and during the follow-up period. Forty of 45 patients (89%) showed abnormal uptake of Tc-99m-MIBI. There was no correlation between intensity of MIBI accumulation and response to chemotherapy. However, patients with negative or decreased MIBI activity 2 h after radionuclide administration showed worse response to chemotherapy compared to those with continued MIBI activity. MIBI activity could not predict the development of relapse in the follow-up study. In this study, the number of patients was small and we could not reach definite conclusions. However, we think that MIBI scintigraphy is not valuable for predicting the chemotherapy outcome in patients with NHL.

Adult↗

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Postoperative radiation therapy for stage IB-IIB carcinoma of the cervix with poor prognostic factors.

BACKGROUND: To investigate failure pattern and to evaluate the prognostic impact of lymph node metastasis in patients with cervical cancer treated with postoperative adjuvant pelvic irradiation. MATERIALS AND METHODS: Ninety-eight patients with FIGO IB to IIB cervical cancer were treated with radical hysterectomy, bilateral pelvic lymphadenectomy and postoperative radiation therapy. All the patients had at least one of the following pathologic risk factors for pelvic recurrence; 1) positive margins, 2) positive pelvic lymph nodes other than common iliac node, 3) deep stromal invasion more than 50% or parametrial invasion. RESULTS: The 5-year overall survival (OAS) rate for the entire patient group was 82%. Causes of the first failure were pelvic recurrence in 5 cases and distant metastasis in 15 cases. Fifteen of the 47 patients with positive pelvic lymph nodes developed distant metastasis, whereas distant metastasis was noted in only 1 of 51 patients without lymph node metastasis. The 5-year OAS rates for patients with and without pelvic lymph node metastasis were 76% and 89%, respectively (p = 0.018). CONCLUSION: Despite receiving postoperative pelvic irradiation, apparently lower survival was observed for node positive patients.

Adult↗

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Chemoradiation for patients with esophageal cancer aged 80 and older.

BACKGROUND: The objectives of this study were to evaluate the efficacy and toxicity of concurrent chemoradiation in patients with esophageal cancer aged 80 and older. PATIENTS AND METHODS: Seven patients with esophageal cancer, aged 80 or more were treated with chemoradiation. Five received a systemic combination of cisplatin and 5-fluorouracil while 2 received daily 5-fluorouracil, concurrent with radiotherapy. The total doses of radiotherapy ranged from 50 to 65 Gy. RESULTS: Complete response was obtained in 3 patients, and partial response and no change in 2 cases each. Esophageal passage improved in 4 patients. The treatment was well-tolerated. There was no death attributable to any adverse treatment effects. None of the patients experienced grade 3 or worse acute toxicities. CONCLUSION: This study demonstrated that advanced age per se is not a sufficient reason to exclude elderly patients from aggressive treatment.

Aged↗

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Aminopeptidase inhibitor ubenimex (bestatin) inhibits the growth of human choriocarcinoma in nude mice through its direct cytostatic activity.

Ubenimex (bestatin), a potent inhibitor of aminopeptidases, is known to have immunomodulatory and host-mediated antitumor activities. In this paper, we investigated the inhibitory effects of bestatin on the growth of human choriocarcinoma both in vitro and in vivo using the established choriocarcinoma cell line NaUCC-4. Bestatin inhibited the in vitro proliferation of NaUCC-4 cells concentration- and time-dependently at more than 72 h incubation. DNA histograms by flow cytometric analysis revealed that exposure to bestatin at 5 to 20 micrograms/ml for 72 h caused mild accumulation of NaUCC-4 cells in the G0/G1 phase of the cell cycle, although no clear arrest was observed in any phase of cell cycle. In vivo antitumor activity of bestatin was examined using the NaUCC-4 choriocarcinoma-xenografted nude mouse model. Tumor growth was significantly inhibited by daily i.p. administration of bestatin for 4 weeks at doses of 2 and 20 mg/kg (p < 0.01 and p < 0.001, respectively), but not by 0.2 mg/kg as compared with control. No significant augmentation of NK activity or B cell mitogenicity in spleen cells taken from these NaUCC-4-hearing nude mice was observed following treatment with bestatin at either 2 or 20 mg/kg. These results indicate that bestatin inhibits the growth of NaUCC-4 choriocarcinoma in vivo as well as in vitro not via potentiation of effector cells but rather by its direct cytostatic activity, and suggest that bestatin may have an additional therapeutic property besides as a BRM for its use in the treatment of choriocarcinoma.

Aminopeptidases↗