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Biomedical subjects

S Imai

Publications and source records attributed to S Imai.

At least 901 records · Page 50Linked to original sources

The inhibitory effect of a conjugate of human immunoglobulin G and melphalan, K18, on DNA synthesis of human tumor cells.

K18 is a conjugate of human immunoglobulin G and melphalan and has been reported to accumulate selectively in the tumor. In the present study, the in vitro antitumor effect of K18 was assessed in a total of 107 fresh human tumors by DNA synthesis (3H-thymidine incorporation) inhibition assay, and compared with that of other drugs. Human tumor cells showed a variety of sensitivities to K18: gastric, breast, pancreatic, liver or ovarian cancer cells were comparatively sensitive to K18, while esophageal or colorectal cancers were insensitive. These results suggest that the conjugation of melphalan with IgG did not reduce the antitumor activity of melphalaln and that K18 may be applied in cancer chemotherapy instead of melphalan.

DNA, Neoplasm↗

Selective accumulation of a new antineoplastic agent, K-18 (human immunoglobulin conjugated melphalan), in Ehrlich carcinoma transplanted in mice.

The absorption of K-18 (human IgG conjugated melphalan) through the intestine and its selective accumulation in the tumor were studied. After oral administration of 14C-melphalan and 14C-K-18 to ICR mice with subcutaneously transplanted Ehrlich carcinoma, K-18 was detected at the tumor site by autoradiogram after 48 hrs, but melphalan was not. Immunofluorescence study showed that orally administered K-18 was absorbed from the intestine via both the portal and the lymphatic route. Moreover, immunoperoxidase staining revealed K-18 in cytoplasm of tumor cells, but not in bone marrow cells. These results demonstrate the absorption of K-18 from the intestine after oral administration and its selective affinity for tumor tissue.

Animals↗

Effects of chronic oral administration of a new beta-blocker, bopindolol, on serum lipoprotein concentrations and blood pressure of spontaneously hypertensive rats.

The effects of chronic oral administration of bopindolol (twice daily for 12 weeks beginning at 5 weeks of age) on serum lipoprotein concentrations, blood pressure and heart rate, were studied in spontaneously hypertensive rats. They were compared with those of two other beta-blockers. Bopindolol and propranolol (15 mg/kg) attenuated the increase in heart rate. Pindolol produced a similar, gradual change in heart rate, but only after the 6th week of treatment. Propranolol and bopindolol attenuated the development of hypertension, whereas pindolol showed no such effect. Pindolol and bopindolol produced a significant increase in high-density lipoprotein cholesterol concentration, but did not produce an increase in serum creatine phosphokinase activity. Administration of these drugs in an acute regimen at 10 weeks of age, provoked changes in blood pressure and heart rate, reflecting partial agonist activities of varying degree, in agreement with the results obtained in chronic experiments with regard to serum lipoprotein concentrations. Pindolol (5 mg/kg) provoked a larger decrease of blood pressure without decrease of heart rate, while the decrease of blood pressure after bopindolol (5 and 15 mg/kg) was associated with a decrease of heart rate. It was concluded that bopindolol is a beta-adrenergic blocking agent with a mild partial agonist activity and devoid of adverse effects on lipid metabolism.

Adrenergic beta-Antagonists↗

Size of normal hilar lymph nodes measured in autopsy specimens.

The normal size of lymph nodes for each region of the hilum was determined by direct measurement of the short and long diameters of each node in the transverse plane of the node and the longitudinal diameter in the vertical plane of the node in 30 adult cadavers. The mean short transverse diameters ranged from 3.2 to 6.4 mm, the mean long transverse diameters ranged from 4.9 to 10.0 mm, and the mean longitudinal diameters ranged from 5.7 to 11.3 mm. The largest mean transverse diameters were found in the anterior upper lobe (AUL) and the inferior interlobar (IIL) regions. We noted a different maximum normal size for lymph nodes in each region of the hilum and determined the standard maximum normal short transverse diameters to be as follows: 12 mm for nodes in the right AUL and IIL regions, 10 mm for nodes in the right superior interlobar region and the left AUL and IIL regions, and 8 mm for nodes in other regions. Both the maximum normal long transverse diameters and the longitudinal diameters showed a wider variation, ranging from 18 to 10 mm and from 20 to 12 mm, respectively.

Adult↗

Effect of ethanol induced occlusion of the renal artery in rabbit kidney implanted with VX2 carcinoma.

The effects of injection of absolute ethanol into the renal artery were investigated in 13 rabbit kidneys previously implanted with VX2 carcinoma. Eight rabbits with implanted tumors served as controls. The effects were evaluated by angiography and histology. Three days after implantation, tumors were demonstrated by angiography as relatively hypovascular areas in the subcapsular cortex of the kidneys. Following angiography, absolute ethanol (0.3 ml/kg) was injected into the renal artery. Repeat angiography with barium sulphate was performed after an additional 3 days (10 ethanol treated animals, 2 controls), 10 days (2 treated, 1 control) or 14 days (1 treated, 0 control). In treated animals the tumors were markedly smaller in comparison with those of the control group. The occlusion procedure, however, did not completely eradicate tumor cells. The histologic study of the implanted tumor confirmed the findings previously reported that viable tumor cells still remained in the peripheral portions of infarcted areas. This study demonstrated the beneficial, though not curative, short-term effects of transcatheter renal artery treatment with absolute ethanol in malignant renal tumors.

Animals↗

In vivo inhibitory effect of a conjugate of immunoglobulin G and melphalan, K18, on human tumors transplanted in nude mice.

Various human tumor lines, including gastric, colonic, esophageal, pancreatic, lung and breast cancer, were transplanted in nude mice, and the effect of K18 (IgG conjugated melphalan) on them was assessed and compared with that of melphalan. Melphalan (1 mg/kg) or K18 (100 mg/kg) were administered to mice for 28 days. The tumor growth was significantly inhibited in 5 out of 6 tumors by both agents, although only the esophageal line was insensitive to both agents. Significant loss of body weight was observed in mice after treatment. K18 had no influence on body weight. These results suggested that K18 may be useful in cancer chemotherapy.

Animals↗

Improvement of pancreaticojejunostomy in pancreatoduodenectomy.

We compared two methods of pancreaticojejunostomy in 36 patients undergoing pancreatoduodenectomy. Pancreatoduodenectomy was performed in 17 men and 19 women aged 35-81 years, including 20 with pancreatic head cancer and 11 with papilla of Vater cancer. Group A (n = 19) underwent pancreaticojejunostomy with a stent tube that was exteriorized via the jejunum. In group B (n = 17), the stent tube ran transhepatically from the pancreatic duct before being exteriorized. The operating time, volume of pancreatic secretions, and time until stent removal were not significantly different between the two groups. However, there were 3 deaths related to early anastomotic leakage and 1 pancreatic fistula in group A, while group B had only 2 spontaneously healing pancreatic fistulas. Our results suggested that the pancreaticojejunostomy method used for group B is superior due to its simplicity, shorter operating time, and better outcome.

Adult↗

Prevalence of human T-cell leukemia virus type 1 (HTLV-I) in family members of adult T-cell leukemia (ATL) patients in non-ATL-endemic Hokkaido of Japan.

Family members of patients with adult T-cell leukemia (ATL) in non-ATL-endemic Hokkaido, the northernmost part of Japan, were assessed for the prevalence of HTLV-I infection. Immunofluorescence assay showed that 53 out of 133 (39.8%) healthy family members of 23 ATL patients were positive for antibodies to HTLV-I. When general inhabitants in Hokkaido were examined, 3 out of 18 (16.7%) family members of 5 seropositive healthy persons had HTLV-I antibodies. The overall seropositivity in Hokkaido was 0.7%. Of 26 family members of 6 patients with non-T-cell leukemia seroconverted by blood transfusion, none (0%) was seropositive.

Adolescent↗

Prevalence of human T-cell leukemia virus type 1 (HTLV-I) in adult T-cell leukemia (ATL) in non-ATL-endemic Hokkaido of Japan.

Sera and peripheral blood lymphocytes of 40 adult T-cell leukemia (ATL) patients in non-ATL-endemic Hokkaido were examined for the prevalence of human T-cell leukemia virus type 1 (HTLV-I). All patients had HTLV-I-specific antibodies. When the peripheral lymphocytes were assessed after short-term cultivation, HTLV-I antigens and virus particles were detected. The seroprevalence in 96 cases of non-T-cell leukemias and lymphomas and in 30,056 healthy individuals in Hokkaido were 3.1% and 0.7%, respectively. HTLV-I seropositive inhabitants of Hokkaido can be estimated at about 40,000, and one out of every few thousand HTLV-I carriers is likely to develop ATL.

HTLV-I Antibodies↗

Prevalence of human T-cell leukemia virus type 1 (HTLV-I) in general inhabitants in non-adult T-cell leukemia (ATL)-endemic Hokkaido, Japan.

In contrast to adult T-cell leukemia (ATL)-endemic southwestern Japan, the northernmost island Hokkaido has a small number of ATL patients annually. In this study, we surveyed 32,587 healthy inhabitants throughout Hokkaido for antibodies to human T-cell leukemia virus type 1 (HTLV-I). Only 244 individuals (0.8%) were seropositive as HTLV-I carriers; 0.6% (123 of 19,512) in males and 0.9% (121 of 13,075) in females. In some areas, however, the inhabitants had relatively high seropositivity (> 2%). The highest rate was 5.2% with a cluster of ATL patients in a certain town of the Hidaka area near the Pacific Ocean, in southeast Hokkaido.

Adolescent↗

Cryptic dysfunction of cellular immunity in asymptomatic human immunodeficiency virus (HIV) carriers and its actualization by an environmental immunosuppressive factor.

Peripheral blood lymphocytes from 4 asymptomatic HIV-1 carriers with normally retained EBV-specific cytotoxic T-cell activity were exposed to EBV and incubated with 0.2 ng/ml 4-deoxyphorbol ester, an immunosuppressive substance derived from an African plant Euphorbia tirucalli. The regression of EBV-induced B-cell transformation by EBV-specific cytotoxic T-cells was significantly impaired in the presence of a small amount of 4-deoxyphorbol ester, but not so in 5 HIV-1-seronegative healthy counterparts. When the EBV-specific cytotoxic T-cells from the asymptomatic carriers were exposed to 0.2ng/ml 4-deoxyphorbol ester and incubated with 51Cr-labeled autologous EBV-transformed B lymphocytes, the released radioactivity was significantly smaller than that of the healthy counterparts. The results suggest that the cellular immunity of the asymptomatic HIV-1 carriers is cryptically impaired, and the cryptic immunological dysfunction is actualized by exposure to a small amount of the immunosuppressive substance, a dose which does not affect the immunity of uninfected healthy individuals.

Adolescent↗

Induction of endometrial adenocarcinomas in persistent estrous Donryu rats by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine.

Induction of endometrial adenocarcinomas in persistent estrous Donryu rats by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) was examined. Female Donryu rats were divided into four groups at 7 weeks of age. Rats in Croup 1 were controls under a 12-h light/12-h dark regimen while Groups 2-4 were persistent estrous animals maintained under 24-h light conditions. At 10 weeks of age, rats in Group 1 and 2 were given a single intra-uterine administration of polyethylene glycol(PEG), and those in Groups 3 and 4 received ENNG(20 mg/kg body weight), dissolved in PEG, in the same manner. Group 4 rats also received an s.c. 17 beta-estradiol(E2) implant one week thereafter. At the termination of the experiment (week 42 after the ENNG-treatment), all surviving rats were killed and the development of uterine proliferative lesions assessed. All groups demonstrated hyperplasias, the incidence and severity being higher in ENNG-treated animals. The incidence of uterine adenocarcinomas in Group 2(2/20, 10%) was slightly higher than that in Group 1(0/16, 0%), although this difference was not significant. In Groups 3(7/19, 37%) and 4(6/20, 30%) statistically significant induction of adenocarcinomas was noted, two lesions in the latter case being very large with prominent invasion of tumor cells into the perimetrium. At 10 and 25 weeks after ENNG-treatment, the E2-progesterone(E2:P) ratios in Groups 2, 3 and 4 were significantly higher than in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Beta-blocking action of bopindolol, a new beta-blocker, and its active metabolites in open chest dogs.

The beta-blocking activity of bopindolol, a new nonselective beta-blocker, and of its active metabolites (18-502 and 20-785) was compared with that of propranolol and atenolol in anesthetized open chest dogs. No remarkable changes in basal cardio-hemodynamic parameters were observed in all groups, except for dp/dtmax which was decreased in the bopindolol-, propranolol-and atenolol-treated groups. All beta-blockers used inhibited the isoproterenol (0.1 microgram/kg, i.v.)-induced tachycardia and the increase in myocardial oxygen consumption dose-dependently. The active metabolite 18-502 was the most potent; it was 19 times as potent as propranolol with respect to the antitachycardic action and 34 times as potent as propranolol in inhibiting the increase in oxygen consumption induced by isoproterenol (0.1 microgram/kg). The potency of bopindolol was nearly equal to that of propranolol, while the potency of atenolol and the metabolite 20-785 was weaker than that of propranolol. As 18-502 was found as a metabolite also in man, it is suggested that 18-502 is a more important active metabolite of bopindolol than 20-785 in in vivo conditions, though the metabolite 20-785 is also a potent beta-blocker.

Adrenergic beta-Antagonists↗

African Burkitt's lymphoma: a plant, Euphorbia tirucalli, reduces Epstein-Barr virus-specific cellular immunity.

Endemicity of Burkitt's lymphoma (BL) coincides with profusion of a plant Euphorbia tirucalli in tropical Africa. E. tirucalli contains 4-deoxyphorbol ester that enhances Epstein-Barr virus (EBV) infection of B lymphocytes. In this study, we found that 4-deoxyphorbol ester reduced EBV-specific cytotoxic T-cell function. Furthermore, the B lymphocytes dually exposed to EBV and 4-deoxyphorbol ester were resistant to EBV-specific T cell cytotoxicity, through down-regulation of latent membrane protein 1 (LMP1), the major target to EBV-specific cytotoxic T-cells. These immunologic findings strengthen the notion that E. tirucalli may be an important environmental risk factor for the genesis of African BL.

Africa↗

Effect of age on the induction of endometrial lesions by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine in F344 rats.

A total of 54 10-week-old or 49 10-month-old female F344 rats were given a single intrauterine administration of 20 mg/kg N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) dissolved in polyethylene glycol (PEG) via the vagina using a non-laparotomy approach. Control animals (32 10-week-old or 29 10-month-old rats) were given PEG alone in the same manner. The animals were killed at 15 and 18 months of age, respectively. One animal in the young treated group presented an endometrial adenocarcinoma (incidence: 2.1%), although the incidence and degree of endometrial hyperplasias were significantly increased in both groups of treated animals, as compared to corresponding controls. Histologically, many of these lesions were polypous glandular hyperplasias (adenomatous polyps) with stromal proliferation. The incidence and grade of proliferative lesions in the young treated group were slightly higher than those in the old treated group. ENNG administration did not appear to affect the hormonal situation in treated animals. These results indicate that young animals may be more sensitive to ENNG than aged ones for induction of endometrial lesions, although ENNG-treatment alone is not sufficient for early and high induction of carcinomas even in young rats of this strain.

Adenocarcinoma↗