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H Otsu

Publications and source records attributed to H Otsu.

At least 19 recordsLinked to original sources

Observation of strong low-lying E1 strength in the two-neutron halo nucleus 11Li.

An exclusive measurement has been made of the Coulomb dissociation of the two-neutron halo nucleus 11Li at 70 MeV/nucleon at RIKEN. Strong low-energy (soft) E1 excitation is observed, peaked at about Ex = 0.6 MeV with B(E1) = 1.42(18) e2fm2 for Erel < or = 3 MeV, which was largely missed in previous measurements. This excitation represents the strongest E1 transition ever observed at such low excitation energies. The spectrum is reproduced well by a three-body model with a strong two-neutron correlation, which is further supported by the E1 non-energy-weighted cluster sum rule.

Journal Article↗

No lengthening of life span in mice continuously exposed to gamma rays at very low dose rates.

Late effects of continuous exposure to ionizing radiation are potential hazards to workers in radiation facilities as well as to the general public. Recently, low-dose-rate and low-dose effects have become a serious concern. Using a total of 4000 mice, we studied the late biological effects of chronic exposure to low-dose-rate radiation as assayed by life span. Two thousand male and 2000 female 8-week-old specific-pathogen-free (SPF) B6C3F1 mice were randomly divided into four groups (one nonirradiated control and three irradiated). Irradiation was carried out for approximately 400 days using (137)Cs gamma rays at dose rates of 21 mGy day(-1), 1.1 mGy day(-1) and 0.05 mGy day(-1) with total doses equivalent to 8000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept under SPF conditions until they died spontaneously. Statistical analyses showed that the life spans of mice of both sexes irradiated with 21 mGy day(-1) (P < 0.0001) and of females irradiated with 1.1 mGy day(-1) (P < 0.05) were significantly shorter than those of the control group. Our results show no evidence of lengthened life span in mice continuously exposed to very low dose rates of gamma rays.

Animals↗

Relative biological effectiveness of carbon ions for causing fatal liver failure after partial hepatectomy in mice.

To evaluate the acute phase damage to liver by carbon ions, BALB/c mice were irradiated with carbon ions or X-rays after two-thirds partial hepatectomy, and their survival was followed. The 50% lethal dose within 60 days (LD50/60) was 42.2 +/- 0.25 Gy (standard error) for X-rays, and 22.7 +/- 0.25 Gy for carbon ions. The relative biological effectiveness (RBE) of carbon ions was 1.86 (95% confident limits: 1.69-2.04) as calculated from the LD50/60. Mice irradiated at much higher doses, 60 Gy of X-rays or 24 Gy of carbon ions, showed significantly higher serum ammonia levels and lower serum albumin levels than normal, suggesting hepatic failure as a cause of death. Hepatocytes showed karyorrhexis and karyolysis in carbon ion irradiated and spotty necrosis in X-ray irradiated mice, suggesting nuclear damage. Mice irradiated with LD50 of X-rays or carbon ions had a remarkably lower bromodeoxyuridine (BrdU) labeling index and mitotic index than control. Treatments with both BrdU and vincristine showed that none of the hepatocytes that synthesized DNA after irradiation completed mitosis, indicating G2 arrest. The liver weight of irradiated mice significantly decreased depending on the dose. Carbon ions as well as X-rays damaged hepatocytes directly and suppressed liver regeneration leading to fatal liver failure.

Ammonia↗

Comparison of dose-dependent enhancing effects of gamma-ray irradiation on urethan-induced lung tumorigenesis in athymic nude (nu/nu) mice ac (nu/+) littermates.

The role of immunological surveillance in carcinogenesis is still controversial. In our previous experiments, urethan-induced lung tumorigenesis in athymic (nu/nu) mice and euthymic (nu/+) littermates was examined, and it was concluded that immunosurveillance mediated by T cells could not be demonstrated. However, the reported enhancement of development of various tumors following ionizing radiation might be achieved through modulating the host immunological conditions. In the present experiment, nu/nu and littermate nu/+ mice were treated with 1-4 Gy gamma-rays alone at 6 weeks of age or treated with urethan at 0.5 mg/g body weight when aged 14 days followed by 1-4 GY gamma-rays 4 weeks later. Lung tumors were assessed at 6.5 months of age. Ionizing radiation itself caused a very low incidence of these lesions. On the other hand, multiplicities and incidences of lung tumors after urethan treatment at 0.5 mg/g body weight were similar between the two phenotypically different groups of mice (1.66 and 1.84 tumors/mouse, 73% and 80% incidences, for nu/nu and nu/+ cases respectively). This urethan-induced lung tumorigenesis was significantly enhanced by gamma-rays in both nu/nu and nu/+ mice, and the magnitude of tumor enhancement was somewhat higher in nu/+ mice than in nu/nu mice, especially with a 2-Gy dose. In conclusion, it may be said that lung tumorigenicity of gamma-ray irradiation itself and the enhancing effect of radiation on urethan-induced tumorigenesis are scarcely influenced by immunosurveillance mechanisms mediated by T cells.

Animals↗

Transmembrane topology and sites of N-glycosylation of inositol 1,4,5-trisphosphate receptor.

To define the transmembrane topology of the inositol 1,4,5-trisphosphate receptor (InsP3R), we determined the subcellular location of the hydrophilic segment (residues 2463-2529 of mouse type 1 InsP3R) believed to be located at the luminal side of the endoplasmic reticulum (ER) in the six-transmembrane model but at the cytoplasmic side in the eight-transmembrane model. This hydrophilic segment includes two consensus sites for N-glycosylation (Asn-2475 and Asn-2503). We prepared an anti-peptide antibody against residues 2504-2523. Electron microscope immunocytochemical studies of mouse cerebellar Purkinje cells showed that binding of this antibody frequently occurs in the intracisternal space of the ER. We constructed three mutant receptors by site-directed mutagenesis of Asn to Gln (N2475Q, N2503Q, and N2475Q/N2503Q). By concanavalin A column chromatography of these receptors, we found that both Asn-2475 and Asn-2503 are glycosylated. These results indicate that residues 2504-2523, Asn-2475, and Asn-2503 are exposed to the ER lumen. We therefore propose that InsP3R has six membrane-spanning segments. Based on the transmembrane topology and subunit organization, we suggest that InsP3R is a member of the superfamily that includes the voltage- and second messenger-gated ion channels on the plasma membrane.

Amino Acid Sequence↗

Comparison of lung tumorigenesis induced by urethan in athymic nude mice and euthymic littermates.

Athymic (nu/nu) and euthymic (nu/+) mice were intraperitoneally given doses of 0.25 to 1.5 mg/g body weight of urethan at the age of 14 to 16 days. Dose-response relationship and sequential changes in lung tumorigenesis induced by urethan in athymic mice were compared with those in euthymic littermates. The urethan dose-response relationship in lung tumorigenesis of the nu/nu mice was almost the same as that in the nu/+ mice. Incidence and multiplicity of the lung tumors were investigated sequentially 28 days to 12 months after urethan injection. They showed similar indexes in the two phenotypically different mice at varying periods after 0.5 mg/g body weight urethan treatment (incidences of 4.8 and 4.4 tumors/mouse and 96 and 97% for nu/nu and nu/+ mice, respectively, at 12 months after treatment). This means that the length of the latent period is similar in these phenotypically different mice. It may be concluded that the immunosurveillance mechanism mediated by T-cells does not function in the present model.

Animals↗

Stacks of flattened smooth endoplasmic reticulum highly enriched in inositol 1,4,5-trisphosphate (InsP3) receptor in mouse cerebellar Purkinje cells.

By immunogold electron microscopy we have shown that in mouse cerebellar Purkinje cells fixed by perfusion with formaldehyde-glutaraldehyde solution, the InsP3 receptor are numerously detected on the stacks of flattened cisterns (OTSU et al, (1990) Cell Struct. Funct., 15: 163-173). In the present experiment we investigated distribution, structure and properties of the stacks by conventional electronmicroscopy, lectin cytochemistry and immunoelectron microscopy. The size and number of stacks were variable depending on their intracellular localization; short stacks with 2-4 parallel cisterns predominate in the perikaryon, long stacks with 4-15 cisterns in the proximal dendrite, and long stacks with 3-4 cisterns in the distal dendrites. The flattened cisterns bind with concanavalin A but not with wheat-germ agglutinin and may contain KDEL proteins loaded with Lys-Asp-Glu-Leu at their C-terminin in their lumens, indicating that the cisterns are derived from ER membranes. The electron dense materials sandwiched between the cisternal membranes are composed of small particles, short cylindrical in shape and approximately 20 nm in diameter, and markedly labeled with anti InsP3R antibody. We suggest that they correspond to the tetramer of the InsP3R or their related molecules. It is not clear whether the stacks of flattened cisterns exist per se in the Purkinje cells or smooth ER existing in singlet in vivo in the Purkinje cells forms stacks during fixation. It is strongly suggested, however, that the smooth ER membranes covered by the InsP3R or their related molecules can easily interact and stack each other in the Purkinje cells.

Animals↗

Effects of preoperative radiotherapy on rectal cancer. Preliminary report on combining radiation with intratumor injections of peplomycin and bromodeoxyuridine.

Between 1976 and 1983, 61 patients with advanced rectal cancer underwent Miles' operation at the authors' institution. All lesions were located 10 cm or less from the anal verge. Of these patients, 25 were treated by surgery alone and 36 were given preoperative radiotherapy. The total dose was 42.6 Gy, (30.6 Gy [1.8 Gy/fr x 5/week]) delivered to the entire pelvis plus an additional 12 Gy (3.0 Gy/fr x 4/week) delivered to the primary tumor. Of 36 patients, 21 were administered intratumor injections of peplomycin and bromodeoxyuridine at the time of boost radiation and 15 were treated without intratumor injections. During the follow-up period (3 to 9 years), in the groups of patients who underwent radiation, there was only one local failure (2.8 percent). In contrast, in the group of patients treated by surgery alone, eight local failures occurred (32 percent). The intratumor injection significantly enhanced the effect of radiation on tumor regression. The incidence of positive lymph nodes was higher in patients in the surgery alone group than it was in the groups treated with radiation. There was no difference in the rate of distant metastasis among the three treatment groups. The five-year survival rate for the radiation with intratumor injection group, radiation alone group, and surgery alone group, was 77.8, 69.2, and 56.0 percent, respectively. No severe complication was experienced.

Adenocarcinoma↗

Immunogold localization of inositol 1, 4, 5-trisphosphate (InsP3) receptor in mouse cerebellar Purkinje cells using three monoclonal antibodies.

Ultrastructural localization of InsP3 receptor in mouse cerebellar Purkinje cells was investigated by immunogold technique using three monoclonal antibodies (mab 10A6, 4C11 and 18A10). The epitopes of the three antibodies were numerously detected on the smooth endoplasmic reticulum (ER) (especially, on the stacks of flattened smooth ER, subsurface cisterns and spine apparatus), scantily on the rough ER and on the outer nuclear membrane, but were not detectable on either the plasmalemma, synaptic densities, mitochondria or Golgi apparatus. Not only mab 4C11 and 10A6 which bind to the N-terminal region of the receptor but also 18A10 which binds to the C-terminal region were localized on the cytoplasmic surface of the ER membranes. This indicates that the C terminus of InsP3 receptor is localized on the cytoplasmic surface of the ER. We noticed that gold particles are usually localized on the fuzzy structure of the cytoplasmic surface of smooth ER, which is suggested to correspond to the feet structure of the ryanodine receptor. In the Nissl body, gold particles were found not only on the ER membranes but also in the cytoplasmic matrix between the rough ER cisterns. We suggest that the peculiar structure of Nissl body, which is composed of parallel cisterns of rough ER, sandwiching a number of free polyribosomes between the cisternal elements, is due to the fact that the major proteins like InsP3 receptor are synthesized mostly on the free polyribosomes and become membrane bound only at the later stage of the biosynthesis.

Animals↗

Radiosensitivity of late recurrences following radiotherapy of murine fibrosarcomas.

Radiosensitivity of late recurrent tumors which emerged after radiotherapy was investigated. Tumors observed were fibrosarcomas. Recurrences emerged in the irradiated area approximately 200 days after a 50% tumor control dose of radiation of 60Co gamma rays or mixed irradiation with fast neutrons and gamma rays. The recurrent and radiation-induced tumors were differentiated by karyotype analysis. Once transplanted into fresh mice, the recurrent tumors grew more slowly than the original tumor. Tumorigenicity of the late recurrences was lower than that of the original tumor. Radiosensitivity of the late recurrences, which was examined using methods to assess control, tumor growth delay, and colony forming assays, was significantly higher than that of the original tumor. D0 values of hypoxic tumor cells were significantly smaller in two of the three recurrences compared to the original tumor. Oxic cells, when irradiated in vitro, also showed smaller D0 values for the recurrent tumors than the original tumor. Hypoxic cell fractions were between 0 and 14% in the late recurrences and 10% in the original tumor. These results are consistent with the hypothesis that radiotherapy causes mutation of tumor cells which results in increased radiosensitivity of surviving tumor cells.

Animals↗

Response of pancreatic tumor to intraoperative radiotherapy: medical imaging and pathologic system approach.

For analyzing the local reaction of pancreatic carcinoma to electron intraoperative radiotherapy, successive computed tomography scanning for tumor volumetry was employed, together with surgical clip localization for tumor area using orthogonal x-rays. Soon after radiotherapy the tumor volume and clipped tumor region began to decrease. After a certain interval, computed tomography volumetry revealed that the irradiated tumor had started to increase in size again, whereas the clipped area had not. Autopsies demonstrated that the increase related chiefly to cancer regrowth outside the primary radiation field.

Aged↗

[The clinical and histopathological effect of combined preoperative radiation and intratumoral injections in rectal cancer].

Twenty-one Surgical patients with carcinoma of the rectum (Group 3) were treated with preoperative radiotherapy and intratumoral injections of Pepleomycin and BUdR (5-bromo-2'-deoxyuridine). On the other hand, 25 patients (Group 1) were treated by surgery alone and 7 patients (Group 2) were treated with preoperative radiotherapy alone. The difference in the background factors of the patients for three groups was not significant. The total dose of preoperative radiation was 42.6 Gy., e.i., 30.6 Gy. (1.8 Gy./fr. X 5/wk) delivered to the entire pelvis plus an additional 12 Gy./fr. X 4/wk) to the primary tumor. The reduction rates in tumor regression on roentgenogram for Groups 2 and 3 were 30.5% and 46.5%, respectively. The extent of cancer cell invasion in rectal wall of the surgical specimens was examined histopathologically. In the preoperative radiation group, especially in Group 3, it was indicated that the stage of the lesion had been reduced. The rates of patients with an "ew" of less than 2mm were 64.0% in Group 1, 28.6% in Group 2 and 14.3% in Group 3 (Group 1-3): p = 0.02). The incidence of positive lymph nodes was higher in Group 1 than in Groups 2 and 3. In a histopathological investigation of the patients in Group 3, the degenerative changes were heavier than in Group 2. Scattered mucocele transformation from the submucosal layer through to the adventitial tissue was noted in Group 3. This study suggests that the clinical and pathological effect of this combination therapy is able to increase the local control and survival rate.

Bleomycin↗

Prognostic significance of pancreatic tumor regression after intraoperative radiotherapy.

Tumor volume measurement using tumor-margin clipping radiography was performed for estimating tumor regression of eight pancreatic adenocarcinomas treated with intraoperative electron irradiation. Half of the tumors regressed exponentially from the first day of treatment, but the other half increased slightly within the first week, after which volume reduction occurred. The volume-halving time was calculated from the regression curve. A wide distribution of volume-halving times as well as initial tumor volumes was seen in all patients. No correlation was found between these variables, but the former correlated well with survival time (r2 = 0.80). This well-known technique may offer a chance to foresee the prognosis of the disease by determining the volume-halving time.

Adenocarcinoma↗

[Acute squamous metaplasia of the whole lung after combined radiation and chemotherapy in advanced lung cancer].

Two patients with advanced lung cancer, histologically diagnosed as adenocarcinoma and squamous cell carcinoma, respectively, were treated with a combination of radiation and anticancer drugs (aclacinomycin-A, bleomycin, mitomycin). The lung tumors responded remarkably to this combined modality. However, the patients succumbed to pneumonia-like disease, being refractory to various antimicrobial treatments. Histologic examination revealed that the outstanding squamous metaplasia developed diffusely in the terminal bronchioles and the alveoli in all lobes of the lungs. Compared with their clinical courses and the resultant detailed pathological findings, the pathogenesis of the conditions was discussed.

Adenocarcinoma↗