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Aim: The occurrence rate of chronic heart failure (CHF) in Japan is estimated to be 50,000 per one million persons. It is important for the Japanese medical financial system to institute a program of disease management in order to prevent the deterioration of persons with CHF. However, there are still few studies on the disease management of CHF in Japan. Therefore, the purpose of this study was to provide an educational self-management program to Japanese outpatients with CHF in order to improve their clinical outcomes., Methods: A randomized, controlled trial with 102 outpatients with CHF was conducted. There were 50 participants in the intervention group and 52 participants in the control group. The control group received medical treatment and standard care. In addition to this, the intervention group also received an educational program for 6 months. The program consisted of six nurse-directed sessions that were provided to each outpatient once per month in a clinical setting for a total of 6 months. A follow-up session was conducted each month for 6 months. The data collection was carried out at the start of the program and at 3, 6, 9, and 12 months., Results: Significant differences could be observed in the primary and secondary outcomes and in the process indicators between the two groups after the program began. In other words, all the indicators improved for the intervention group, compared to the control group. Therefore, this program was considered to be effective., Conclusion: Further long-term care is necessary for outpatients with CHF in order to prevent their deterioration and to maintain their health status, even though this 6 month program did provide them with proper knowledge regarding self-care for CHF and affected their therapy results., (© 2010 The Authors. Japan Journal of Nursing Science © 2010 Japan Academy of Nursing Science.)

The cross sections for single-neutron removal from the very neutron-rich nucleus 31Ne on Pb and C targets have been measured at 230 MeV/nucleon using the RIBF facility at RIKEN. The deduced large Coulomb breakup cross section of 540(70) mb is indicative of a soft E1 excitation. Comparison with direct-breakup model calculations suggests that the valence neutron of 31Ne occupies a low-l orbital (most probably 2p(3/2)) with a small separation energy (S(n) approximately < 0.8 MeV), instead of being predominantly in the 1f(7/2) orbital as expected from the conventional shell ordering. These findings suggest that 31Ne is the heaviest halo system known.

An excited state in the proton-rich unbound nucleus 12O was identified at 1.8(4) MeV via missing-mass spectroscopy with the 14O(p,t) reaction at 51 AMeV. The spin-parity of the state was determined to be 0+ or 2+ by comparing the measured differential cross sections with distorted-wave calculations. The lowered location of the excited state in 12O indicates the breakdown of the major shell closure at Z=8 near the proton drip line. This demonstrates the persistence of mirror symmetry in the disappearance of the magic number 8 between 12O and its mirror partner 12Be.

We report on the first spectroscopic study of the N=22 nucleus 32Ne at the newly completed RIKEN Radioactive Ion Beam Factory. A single gamma-ray line with an energy of 722(9) keV was observed in both inelastic scattering of a 226 MeV/u 32Ne beam on a carbon target and proton removal from 33Na at 245 MeV/u. This transition is assigned to the deexcitation of the first Jpi=2+ state in 32Ne to the 0+ ground state. Interpreted through comparison with state-of-the-art shell-model calculations, the low excitation energy demonstrates that the "island of inversion" extends to at least N=22 for the Ne isotopes.

Four thousand 8-week-old SPF B6C3F1 mice (2000 of each sex) were divided into four groups, one nonirradiated (control) and three irradiated. The irradiated groups were exposed to (137)Cs gamma rays at dose rates of 21, 1.1 and 0.05 mGy day(-1) for approximately 400 days with total doses equivalent to 8000, 400 and 20 mGy, respectively. All mice were kept until natural death, and pathological examination was performed to determine the cause of death. Neoplasms accounted for >86.7% of all deaths. Compared to the nonirradiated controls, the frequency of myeloid leukemia in males, soft tissue neoplasms and malignant granulosa cell tumors in females, and hemangiosarcoma in both sexes exposed to 21 mGy day(-1) were significantly increased. The number of multiple primary neoplasms per mouse was significantly increased in mice irradiated at 21 mGy day(-1). Significant increases in body weights were observed from 32 to 60 weeks of age in males and females exposed to 1.1 mGy day(-1) and 21 mGy day(-1), respectively. Our results suggest that life shortening (Tanaka et al., Radiat. Res. 160, 376-379, 2003) in mice continuously exposed to low-dose-rate gamma rays is due to early death from a variety of neoplasms and not from increased incidence of specific neoplasms.

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.

The induction of oxidative stress in pulmonary cells during the process of lung tumor promotion by dimethylarsinic acid (DMA), a main metabolite of inorganic arsenics in mammals, was examined by immunohistochemical analysis using a specific antibody against 4-hydroxy-2-nonenal (4HNE) adducts, which are major aldehydic metabolites of lipid peroxidation. We demonstrated that 4HNE-modified proteins existed specifically in the secretory granules in terminal bronchiolar Clara cells. Furthermore, the degree of positive staining increased with the duration of DMA administration. Transmission electron microscopy revealed morphological changes in the Clara cells of DMA-treated mice. These results suggest that Clara cells are the major target cell for DMA-induced oxidative stress and that the cells may play an important role in the lung tumor promotion process in mice.

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.

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.

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.

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.

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.

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.

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.

Twenty-three patients with carcinoma of the hepatic hilus, including the upper one-third of the extrahepatic bile duct, were treated by surgical resections. Gross appearances of this lesion are classified into polypoid, nodular, schirrhous constricting and diffusely infiltrating types. Each type has a different resectability and prognosis from the macroscopic point of view. The cell type in all patients was adenocarcinoma. Operation was curative in 100 per cent of four patients with the polypoid type. The chance for survival was definitively better for patients with this type than with the other three. Preoperative percutaneous transhepatic cholangiography as well as endoscopic retrograde cholangiography and celiac angiography can provide an excellent index to the resectability of the tumor and prognosis. Our experience suggests that gross appearance of the tumor may be valid as a prognostic factor in the treatment of the lesion.

When Nil2C2, a metastatic clone derived from hamster embryo fibroblasts (Nil), was inoculated over [3H]leucine-labeled fixed cells, Nil2C2 cells solubilized and phagocytosed fixed cells, and the radioactivity was released into the culture medium as trichloroacetic acid-soluble fragments. The solubilization of fixed cells was dependent on both the time of incubation of living cells with fixed cells and the number of living cells inoculated. Nil2C2 cells were shown by autoradiographic and electron microscopic studies to peel off fixed cells and ingest them as large fragments. The solubilization of fixed cells was significantly decreased when plasminogen was depleted from the culture medium. Protease inhibitors such as leupeptin, epsilon-aminocaproic acid, and soybean trypsin inhibitor partially inhibited the proteolysis and phagocytosis of Nil2C2 cells. Mouse peritoneal macrophages activated by Salmonella typhimurium solubilized fixed cells after the addition of 12-O-tetradecanoylphorbol-13-acetate. However, they did not phagocytose fixed cells as large fragments.

The choledochoscopic photographs of 91 and 119 patients with cholecystolithiasis and choledocholithiasis respectively were reviewed on the basis of endoscopic grading. By analogy with the system of the grading, the diseases were also divided into four histopathological gradings. Choledochoscopy provides an alternative approach to the diagnosis of choledochitis, which is also corroborated by the histopathological data in calculous diseases.

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.

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.

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.

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.

During the period of November 1976 through October 1984, we have treated 46 patients with carcinoma at the confluence of the major hepatic ducts. Curative resection of the tumor (where no carcinoma cells at the margin of the resected portion were found macroscopically and microscopially), was performed upon ten patients, palliative resections were done in 11, palliative resection and intraoperative radiotherapy (IOR) in ten, bile duct drainage and IOR in three, and percutaneous transhepatic cholangiodrainage in 12. Among the ten patients who underwent curative operation, five are living six to 104 months after operation while the remaining five died four to 72 months postoperatively. Of the 11 patients who underwent palliative resection, five are alive two to 22 months after operation and six died between four and 20 months after operation. For the ten patients with carcinoma in the advanced stages, palliative resection with IOR was performed. Eight patients died 20 days to 16 months after operation while two patients are alive 13 and 14 months after the procedure. Of the three patients who underwent drainage of the bile duct and IOR, two died three months after operation and one patient survived 34 months. Twelve patients underwent drainage of the bile duct only and all died after 13 months. To perform a curative operation for carcinoma located at the confluence of major hepatic ducts, it is necessary to resect the right or left lobe, including the caudate lobe, in many instances. For the patients with carcinoma in the advanced stages, the possibility of long term survival period after operation exists through the use of the combined techniques of IOR and palliative resection of the tumor.

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.

Computed tomography was used in 7 patients given intraoperative electron beam therapy for advanced carcinoma of the pancreas. The local tumor response was studied quantitatively by defining the tumor contour in consecutive CT scans and then estimating the tumor volume. The maximum diameters of the tumor in 3 planes (X, Y and Z) were also estimated. There was evidence of initial tumor regression in all patients during the first few months after the treatment. No specific behaviour of the diameters in the X, Y and Z planes could be detected. Later on, regrowth of the tumor could sometimes be observed, preferably in one of the 3 planes. On the whole, CT was found to be a useful tool for assessing tumor response to this form of therapy.

A detailed retrospective analysis of the efficacy of intraoperative radiotherapy (IOR) in advanced carcinoma of the pancreas is presented. During a 10-year period from 1973 through 1982, 70 patients with advanced carcinoma of the pancreas were treated by multimodal methods, separate or combined therapy of surgery, IOR, and chemotherapy in two different institutions. Among these, 33 patients underwent IOR, mostly combined with additive surgery. A single dose of 20.1 to 40.0 Gy with 8 to 25 meV electrons was delivered through radiation cones ranging from 6 to 10 cm in diameter. Excellent relief was noticed in 50% of the patients who had complained of pain. Among Stage IV patients, a significant difference of survival rate was observed between IOR and control groups (P less than 0.05); the mean survival time of the IOR group was 4.6 +/- 2.6 (SD) and that of the control group 2.5 +/- 1.4 (SD) months. Intraoperative radiotherapy proved to be effective in prolonging the survival of patients with advanced stage of the lesion.

Forceps biopsy of the distal part of the common bile duct was performed in 27 patients with cholelithiasis, under choledochoscopic guidance during surgery. Significant choledochitis was diagnosed in 72 per cent of the patients, including two with carcinoma of the head of the pancreas. Two patients with carcinoma of the head of the pancreas underwent biopsy in an attempt to obtain evidence of neoplasm. Furthermore, one patient suspected of carcinoma of the left hepatic duct tributaries received the same treatment and the malignancy was confirmed. No complications occurred. The prime indication for biopsy is to prove the presence of malignancy at this region and to provide an index for the management of cholangitis combined with choledocholitiasis.