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This study was a prospective, multicentre, cohort study on 685 patients who had undergone oncologic surgery. The patients were divided into two groups according to the presence or absence of postoperative pneumonia. The two groups were compared with respect to their background, index operation, food eaten, oral condition, contents of oral care and dental treatment, laboratory data, and bacterial flora. All postoperative pneumonias occurred in six cases within four days postoperatively. The multivariable logistic regression analysis showed that preoperative serum C-reactive protein was the strongest predictor of postoperative pneumonia. In addition, decreased postoperative Candida albicans colonies was an effective predictor of postoperative pneumonia. For patients with predictors of postoperative pneumonia, perioperative strategies for its prevention should be considered in addition to professional oral health care. This study was approved by the National Hospital Organization’s Central Ethics Review Board and was also approved by the directors of the participating institutions.

We present a method for improving the search accuracy of the similar typhoon research system by leveraging deep neural networks, which are an extension of artificial neural networks. To the search engine, we apply three parameters of typhoons: course, temporal central pressure, and speed. We show that these parameters can improve accuracy when searching for past typhoons having characteristics similar to the target. Furthermore, the accuracy of functions designed to support the expected disaster prevention actions and flood fighting services was assessed based on the results from the search system.

River administration in Japan requires the ability to predict flooding events and to respond to them with appropriate judgment and action. The accuracy of systems for flood prediction modeling, which have been studied by the authors, has been increased with a new approach developed by the authors. We have developed a system for analyzing flood data from past typhoons and other flood disasters. We utilize this data to identify and prioritize the important duties of river managers during predicted typhoons. These prioritized duties are arranged into timeline-based disaster prevention action plans. This paper describes the design and development of a support system used to analyze flood data for disaster prevention and action plans. We specifically developed a typhoon search and prediction system, which utilized neural network modeling, for flood fighting, based on disaster prevention and action plans.

A search for new proton-rich isotopes using projectile fragmentation of a 345-MeV/nucleon 124Xe beam has been performed with the BigRIPS in-flight separator at the RIKEN Nishina Center RI Beam Factory. Projectile fragments were identified by measuring the time of flight, magnetic rigidity, and energy loss in the BigRIPS separator. Projectile fragments then were transported downstream of the BigRIPS separator and re-identified by measuring the time of flight and total kinetic energy. Through such particle re-identification, we have discovered four new isotopes 81,82Mo and 85,86Ru located near the proton drip line. The 76Y and 78Zr isotopes near the proton drip line also were identified, supporting the previous report on their discovery. Furthermore, we have obtained the first clear evidence for the particle instability of 103Sb. Based on the systematics of measured production yields, the upper limit values were evaluated for the half-lives of the particle-unbound isotopes 81Nb,85Tc, and 103Sb.

Very neutron-rich $Z\ensuremath{\sim}60$ isotopes produced by in-flight fission of a 345 MeV/nucleon $^{238}\mathrm{U}$ beam at the RI Beam Factory, RIKEN Nishina Center, have been studied by delayed $\ensuremath{\gamma}$-ray spectroscopy. New isomers were discovered in the neutron-rich $N=100$ isotones $^{162}\mathrm{Sm}, ^{163}\mathrm{Eu}$, and $^{164}\mathrm{Gd}$. Half-lives, $\ensuremath{\gamma}$-ray energies, and relative intensities of these isomers were obtained. Level schemes were proposed for these nuclei and the first ${2}^{+}$ and ${4}^{+}$ states were assigned for the even-even nuclei. The first ${2}^{+}$ and ${4}^{+}$ state energies decrease as the proton numbers get smaller. The energies and the half-lives of the new isomers are very similar to those of ${4}^{\ensuremath{-}}$ isomers known in less neutron-rich $N=100$ isotones $^{168}\mathrm{Er}$ and $^{170}\mathrm{Yb}$. A deformed Hartree-Fock with angular momentum projection model suggests ${K}^{\ensuremath{\pi}}={4}^{\ensuremath{-}}$ two-quasiparticle states with $\ensuremath{\nu}7/2[633]\ensuremath{\bigotimes}\ensuremath{\nu}1/2[521]$ configurations with similar excitation energy. The results suggest that neutron-rich $N=100$ nuclei are well deformed and the deformation gets larger as $Z$ decreases to 62. The onset of $K$ isomers with the same configuration at almost the same energy in $N=100$ isotones indicates that the neutron single-particle structures of neutron-rich isotones down to $Z=62$ do not change significantly from those of the $Z=70$ stable nuclei. Systematics of the excitation energies of new isomers can be explained without the predicted $N=100$ shell gap.

We measured the reaction cross sections of the two-neutron halo nucleus 14Be with proton and carbon targets at about 41 and 76 MeV/nucleon. Based on a Glauber model calculation, we deduced the matter density distribution of 14Be in which previously measured interaction cross sections at relativistic energies were also included. An s-wave dominance in 14Be has been confirmed, although the halo tail of 14Be is not distributed as much as that of 11Li. Significant mixing of the p-wave in addition to the s- and d-wave is also suggested.

Reaction cross sections with various kinds of breakup channels for neutron-rich carbon isotopes 18–20C and for 9Be impinging on a liquid hydrogen target were investigated at 40 MeV/nucleon. The nuclides of interest were produced via projectile fragmentation from a 63 MeV/nucleon 40Ar beam and were separated in flight at the RIKEN projectile fragment separator (RIPS). The combination of the large-acceptance superconducting TOF spectrometer, TOMBEE (TOF Mass analyzer for exotic BEam Experiment), with a liquid hydrogen target, CRYPTA (CRYogenic ProTon and Alpha target system), enables simultaneous measurements of several reaction channels: the reaction cross sections ( σ R ), individual elemental fragmentation cross sections ( σ Δ Z ), charge-changing cross sections ( σ cc ), neutron-removal cross sections ( σ − x n ), and charge-pickup cross sections ( σ Δ Z + 1 ) for 19,20C; σ Δ Z , σ − x n , and σ Δ Z + 1 for 18C; and σ R for 9Be. The present σ R of 9Be on proton, σ R = 397 ± 23 mb , measured in the inverse kinematics, was consistent with the previous measurements using proton beams at different laboratories. The σ R of 19C and 20C on proton were determined to be σ R = 754 ± 22 mb and σ R = 791 ± 34 mb , respectively. Taking into account the beam energy and target dependence of σ R , the present σ R are found to be considerably enhanced compared with those measured at around 1 GeV/nucleon. The σ Δ Z + 1 appears to increase with the mass number of the projectiles, and it significantly contributes to σ R in the present energy range. The finite-range optical-limit and few-body Glauber model analyses were performed for σ R to study the nuclear matter density distributions and to derive the relative strength of the s-wave components of the valence neutrons in 19C and 20C. A neutron halo structure of 19C is confirmed with an s-wave dominance of the valence neutron when the effect of the charge-pickup reaction is taken into account. The large σ − n of 19C and σ − 2 n of 20C also support the decoupled structures of 18C +n and 18C + 2 n , respectively. The σ cc of 19C and 20C agree with each other within their experimental uncertainties, which might indicate a similar proton density distribution in 19C and 20C. The σ Δ Z decreases monotonically without the even–odd effect as the number of removed protons increases.

We report recent situation of anomaly in spin expectation value found in 9 C- 9 Li mirror pair, recent analysis of the nuclear spin in terms of orbital or intrinsic and proton or neutron, and a result from the study of the G -parity conservation law through β -ray angular correlation in terms of its nuclear orientation.

Interaction cross sections ( σ I ) for neutron-rich Ne isotopes, 28–32Ne on C target have been measured at 240A MeV using the RIBF at RIKEN. A large enhancement of σ I beyond the systematics of stable nuclei have been observed for neutron-rich Ne isotopes, particularly for 31Ne. The possible halo structure for 29,31Ne which would be caused by the lowering of the pf-shell and nuclear deformation of Ne isotopes are discussed by the preliminary analysis.

CS-1008, a humanized monoclonal antibody that is agonistic to human death receptor 5, was intravenously administered to cynomolgus monkeys twice a week for 13 weeks at 3 different dose levels (5, 15 and 42 mg/kg) in order to evaluate its potential toxicity. A control group received phosphate buffered saline containing 0.01% polysorbate 80. Each of the 4 groups consisted of 3 male and 3 female cynomolgus monkeys. No animal in any group died during the dosing period. No toxic changes in clinical signs, food consumption, body weight, electrocardiography, ophthalmology, urinalysis, hematology, blood chemistry, gross pathology, organ weights or histopathology were noted in any group during the dosing period. In the toxicokinetic analysis, the values for the maximum concentration of CS-1008 in plasma and the area under the curve generally increased with increasing dose. No clear differences in the toxicokinetic parameters or profiles were observed between the sexes. Development of anti-CS-1008 antibodies was not detected in any sample. The no-observed adverse-effect level (NOAEL) of CS-1008 in cynomolgus monkeys under the conditions of this study was concluded to be 42 mg/kg in both sexes, when administered intravenously twice a week for 13 weeks. This study supports the development of CS-1008 as a therapeutic biopharmaceutical.

A 23-year-old woman was admitted to our department because of gait disturbance, sensory impairment in the lower limbs, and sphincter disturbance, all of which had been developing within 24 hours before admission. Neurological examination disclosed symmetric muscle weakness, sensory impairment, and diminished tendon reflexes in the lower limbs. The urinary bladder was hypoactive, and the anal tone was reduced. The spinal cord MRI performed on the day of admission revealed swelling of the epiconus. The CSF findings were not remarkable, except for the elevated levels of IgE (8 IU/ml) and MBP (7.8 ng/ml). Besides, there was a marked increase in the serum mite-specific IgE titers. Collectively, we made a diagnosis of atopic myelitis. She was treated with steroid pulse therapy and plasma exchange, which led to a significant amelioration of her neurological manifestations. The repeat MRI carried out on the 21st day of her admission displayed several foci scattered in the lumbar and sacral spinal cord segments, which exhibited high intensity signals on the T2-weighted images. The values of IgE and albumin in the CSF and serum raised the possibility of intrathecal IgE synthesis. We measured her CSF IgE levels at several time points during admission. The temporal profile of her CSF IgE levels was not correlated with that of her neurological disabilities.

Introduction Drug-induced QT prolongation is a major safety issue during drug development because it may lead to lethal ventricular arrhythmias. In this study, we evaluated the utility of multi-electrode arrays (MEA) with human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to predict drug-induced QT prolongation and arrhythmia. Methods Ten facilities evaluated the effects of 7 reference drugs (E-4031, moxifloxacin, flecainide, terfenadine, chromanol 293B, verapamil, and aspirin) using a MED64 MEA system with commercially available hiPS-CMs. Field potential duration (FPD), beat rate, FPD corrected by Fridericia's formula (FPDc), concentration inducing FPDc prolongation by 10% (FPDc 10 ), and incidence of arrhythmia-like waveform were evaluated. Results The inter-facility variability of absolute values before drug application was similar to the intra-facility variability for FPD, beat rate, and FPDc. The inter-facility variability of FPDc 10 for 5 reference drugs ranged from 1.8- to 5.8-fold. At all 10 facilities, E-4031, moxifloxacin, and flecainide prolonged FPDc and induced arrhythmia-like waveforms at concentrations 1.8- to 6.1-fold higher than their FPDc 10 . Terfenadine prolonged FPDc and induced beating arrest at 8.0 times the FPDc 10 . The average FPDc 10 values for E-4031, moxifloxacin, and terfenadine were comparable to reported plasma concentrations that caused QT prolongation or Torsade de Pointes in humans. Chromanol 293B, a I Ks blocker, also prolonged FPDc but did not induce arrhythmia-like waveforms, even at 7.4 times the FPDc 10 . In contrast, verapamil shortened FPDc and aspirin did not affect FPDc or FP waveforms. Discussion MEA with hiPS-CMs can be a generalizable method for accurately predicting both QT prolongation and arrhythmogenic liability in humans.

The one-neutron knock-out reaction $^{1}\mathrm{H}(^{20}\mathrm{C},^{19}\mathrm{C}\ensuremath{\gamma})$ was studied at RIKEN using the DALI2 array. A $\ensuremath{\gamma}$-ray transition was observed at 198(10) keV. Based on the comparison between the experimental production cross section and theoretical predictions, the transition was assigned to the de-excitation of the $3/{2}_{1}^{+}$ state to the ground state.

Hyperlipidemic ocular lesions are described for Watanabe heritable hyperlipidemic (WHHL) rabbits. Male WHHL rabbits 8 months old exhibited serum hyperlipidemia and ophthalmoscopically yellowish-white lesions along the corneoscleral junction and in the iris. Histopathologically, foamy macrophages aggregated in the stroma of the cornea, iris, and ciliary body were observed. These findings have been interpreted as lipid keratopathy. In addition, multiple clusters of a large number of foamy macrophages occurred throughout the choroid and sclera in association with the blood vessels. The lesions in the choroid and sclera could not be detected ophthalmoscopy, yet were much more prominent than those in the cornea, iris, and ciliary body, suggesting greater involvement and earlier onset of lipidosis at these sites associated with hyperlipidemia in WHHL rabbits.

It has often been observed that chemical-induced initial insult is no longer detected in examinations after additional consecutive treatments, suggesting that the target organs acquire resistance to chemical toxicity. In this study, we examined whether acquired resistance to toxicity would be observed after repeated treatments of a toxic dose of bromobenzene (BB). In Experiment 1, F344 male rats were intraperitoneally given BB at a dosage of 150 mg/kg/day. Based on the serum AST level 20 h after the first treatment, the rats were divided into 2 groups, Groups 2 and 3, which consisted of rats with elevated AST and rats without remarkable changes in AST activity, respectively. Subsequently, the rats were subjected to the same BB treatment regimen for 4 or 9 consecutive days. The control group (Group 1) was administered with the vehicle. The AST activity of Group 2 showed no remarkable changes from Day 3, indicating an acquired resistance to BB hepatotoxicity. Measurements of drug-metabolizing enzymes in Group 2 demonstrated a reduction in CYP contents and activities, and a strong induction of GST, which contributed to the resistance. The aminotransferase activities in Group 3, however, showed no changes throughout the dosing periods. In Experiment 2, the rats with the same BB treatment regimen as Experiment 1 were administered intraperitoneally with a single dosage of BB of 300 mg/kg. Although a higher dosing of BB caused hepatic injury in all three groups, the degree of injury in the two groups with BB treatment was much slighter than that in the control (vehicle + BB). These results indicate that not only Group 2 but also Group 3 acquired resistance to BB hepatotoxicity after repeated treatments. The exposure levels of BB in the two groups were lower than those of the control. Thus, changes in the drug-metabolizing reaction related to the metabolism and detoxification of BB contributed to the resistance to BB hepatotoxicity.

The mRNA profiles for peroxisome proliferator activated receptor (PPAR) alpha and human c-Ha-ras genes were determined by real-time semi-quantitative polymerase chain reaction analysis of hepatocellular adenomas induced by di(2-ethylhexyl)phthalate (DEHP) in transgenic mice carrying a human prototype c-Ha-ras gene (rasH2 mice). The mRNA levels were essentially equal in hepatocellular adenomas and adjacent non-neoplastic hepatocytes, in spite of a remarkable elevation in the cell proliferation index in tumors determined by anti-Ki-67 immunohistochemistry. From the results, it is concluded that overexpression of PPARalpha or the transgene is not associated with the liver tumorigenesis induced by DEHP in rasH2 mice.

L-buthionine (S,R)-sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, was administered to mice via drinking water for 14 days in order to establish an animal model with continuously depleted levels of GSH. No toxicity was observed at 20 mM BSO, even though a significant decrease in liver weight was observed at 30 mM BSO. GSH levels in the liver, kidney, brain, lung, heart, spleen, pancreas, small intestine, large intestine, skeletal muscle, plasma and blood cells from mice given 20 mM of BSO were all less than those from the control mice continuously throughout a 24-hr period. The ratios of the GSH levels to that of the control were 46.4% and 16.7% in the liver and kidney, respectively, suggesting a decrease in GSH conjugation activity in vivo by GSH depletion. Liver cytochrome P450 content and UDP-glucuronosyltransferase activity to p-nitrophenol were not influenced by the BSO dosing. To confirm the adequacy of this GSH-depletion model, 0.125 or 0.25% of acetaminophen (APAP) was administered via diet to this model for 14 days. Nine out of the ten mice given both 20 mM BSO and 0.25% APAP died on Day 2, and remarkable necrosis was observed in the hepatocytes and renal tubular epithelium. Moreover, focal necrosis of hepatocytes with proliferation of fibroblasts was observed on Day 15 in some mice coadministered 20 mM BSO and 0.125% APAP. However, no toxicity was observed in mice given APAP alone. Based on these results, a mouse given 20 mM of BSO via drinking water for 14 days was concluded to be an animal model with continuously depleted levels of GSH in various organs without toxicity. This model shows high susceptibility to toxicity induced by chemicals which are metabolized to electrophilic and reactive metabolite(s), such as APAP.

This paper describes the locating system of line-to-ground faults on a transmission line by wavelet transform. The possibility of the location with the surge generated by a fault has been theoretically proposed. In order to make the method practicable, we realize very fast processors. We design wavelet transform and location chips, and construct a very fast fault location system by processing the measured data in parallel. This system is realized by a computer with three FPGA processor boards on a PCI bus. The processors are controlled by UNIX and the system has the graphic user interface with X window system. © 2002 Wiley Periodicals, Inc. Electr Eng Jpn, 140(4): 27–37, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10040

The total charge-changing, charge pick-up, and partial charge-changing cross sections of very neutron-rich nuclei (Ne-30, Na-32,Na-33) with a proton target have been measured at similar to 240A MeV for the first time. We introduced the phenomenological correction factor in Glauber-model calculations for the total charge-changing cross sections with the proton target, and applied it to deduce the proton radii of these nuclei. For 30Ne and Na-32, the neutron skin thicknesses of the nuclei were deduced by comparing the proton radii with the matter radii deduced from the interaction cross-section measurements. A significant thick neutron-skin has been observed for the nuclei. We also found that the charge pick-up cross sections are much larger than those in the systematics of stable nuclei.

A half-metallocene-type complex, La(C5Me5)[CH(SiMe3)2]2tetrahydrofuran (THF) 1, showed the dual function of performing the controlled polymerizations of nonpolar monomers such as ethylene and styrene as well as polar monomers like methyl methacrylate, hexyl isocyanate, and acrylonitrile in high yields. On the other hand, the metallocene-type rare-earth metal complexes, [(C5H4SiMe3)2Y(μ-Me)]22 and (C5Me5)2YMe(THF) 3, showed relatively low catalytic activity. The structure of complex 2 was characterized by X-ray analysis. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1382–1390, 2001

A novel rat model of hereditary renal cell carcinoma (RC) was found in a rat colony of the Sprague-Dawley strain in Japan, and named the rising "Nihon" rat. In this strain, RCs develop from early preneoplastic lesions, which begin to appear at 4 weeks of age, forming adenomas by the age of 16 weeks. The RCs are predominantly of clear cell type. Southern blot, northern blot and SSCP analyses revealed no change in the Tsc1, Tsc2, VHL, and c-Met genes. Thus, the Nihon rat should be a valuable experimental model for understanding renal carcinogenesis, especially clear cell type, which is common among human RCs.

A mucinous adenocarcinoma was found in the jejunum of an untreated male F344 rat of 126 weeks old. The neoplasm was primarily composed of cuboidal to columnar goblet cells that were arranged in a glandular form. Alcian blue-PAS staining revealed mucin in neoplastic cells and in the lumen. Paneth cells were found scattered among the goblet cells together with metaplastic cartilage and bone formation in the interstitium.

The ratio of urinary 6beta-hydroxycortisol (6beta-OHF) to free cortisol (F), i.e., the 6beta-OHF/F ratio, has been reported to be a specific marker for human CYP3A induction by in vivo studies of human subjects. In the development of drugs, it is quite beneficial to predict human CYP3A induction in preclinical safety studies using urine samples from experimental animals. We examined the 6beta-OHF/F ratio in urine of common marmosets administered with rifampicin, a potent inducer of CYP3A, to evaluate the usefulness of common marmosets for the prediction of CYP3A induction. Rifampicin was orally administered to three groups of four male common marmosets at doses of 0, 10, and 20 mg/kg per day for 4 days. Amounts of 6beta-OHF and F in urine samples were determined by means of high-performance liquid chromatography (HPLC) during the experimental period. One day after the 4th dosing, animals were killed, and P450 contents and P450-catalyzed. 7-alkoxycoumarin O-dealkylase (ACD) activities in the liver were measured. Western blot analysis of liver microsomes was also performed using anti-rat P450 (CYP1A1, 2B1/2, 3A, and 4A) antibodies. The results indicated elevations in the 6beta-OHF/F ratios that were dependent on both the dosing period and dose levels adopted. The ratios on day 4 reached 4.7- and 5.3-fold the pre-administration values in the 10 and 20 mg/kg per day groups, respectively. P450 contents and ACD activities were also elevated in all of the groups. Western blot analysis showed specific increases in the protein which cross-reacts with anti-rat CYP3A antibody in all of the groups. Furthermore, the 6beta-OHF/F ratio was well correlated with the CYP3A contents in liver (r = 0.906). These results indicated that increase in urinary excretion of 6beta-OHF is a specific marker of the induction of hepatic CYP3A in common marmosets just as in humans. Consequently, the present study suggested that human CYP3A induction elicited by chemical agents can be predicted in common marmosets by measuring the urinary excretion of 6beta-OHF.

Mini rats, a Wistar-derived transgenic rat strain harboring a rat growth hormone (GH) antisense gene, show lower plasma GH levels than Wistar rats. In our previous study, Mini rats showed a smaller femur size with lower mineral density and a reduction of the metaphyseal and diaphyseal bone mass at 8 and 22 weeks of age. In the present study, we examined the femur and tibia from Mini rats and Wistar rats at 10 to 60 weeks of age, and we performed cancellous and cortical bone histomorphometry on the tibia to examine the status of bone turnover. We found that the bone size, mineral content, and mineral density of the femur and tibia were significantly lower in Mini rats and tended to increase in both strains until 38 or 60 weeks of age. The longitudinal growth rate was significantly higher in Wistar rats until 26 weeks of age, and at 38 weeks of age that in Wistar rats is comparable to that in Mini rats. The periosteal bone formation rate tended to be higher in Wistar rats until 60 weeks of age. The longitudinal growth rate in both strains and the periosteal bone formation rate in Wistar rats tended to decrease with age. In contrast, bone turnover in the secondary spongiosa of the proximal tibial metaphysis showed no apparent difference between the two strains and seemed to remain unchanged until 60 weeks of age. Therefore, it is suggested that the reductions of bone mass in the metaphysis and diaphysis in Mini rats may be attributable to the lower longitudinal growth rate and periosteal bone formation rate, and that GH may influence bone modeling but not bone remodeling.

Growth hormone (GH) plays an important role in longitudinal bone growth, and hypophysectomized rats have generally been used as a model for GH deficiency in humans. Recently, researchers have bred Mini rats, a Wistar-derived transgenic rat strain harboring a rat GH antisense gene and showing lower plasma GH levels than Wistar rats. In a previous study, Mini rats showed a smaller femur size with lower mineral density and a reduction of the metaphyseal and diaphyseal bone mass. In the present study, Wistar rats were hypophysectomized (HX) and treated with GH, and then their bones were examined and compared with vehicle-treated intact age-matched Wistar rats and Mini rats. GH-treated (HX+GH) rats exhibited an increase in the mineral density of the tibia and increases in the length and mineral content of the femur and tibia. These changes in the HX+GH rats were attributable to an increase in the longitudinal growth and periosteal bone formation of the femur and tibia. When Mini rats and HX rats were compared with Wistar rats, both animals showed similar reductions in the bone length, mineral content, and mineral density of the femur, but the Mini rats showed a greater longitudinal growth rate, cancellous bone mass, and mineralizing surface than the HX rats, as well as less remarkable changes in body weight, relative organ weights, and hematological and blood chemical parameters. Therefore, Mini rats are considered to be a useful model for clarifying features of GH deficiency and examining effects of various treatments on the bone without any specific surgery or drug-administration.

Growth hormone (GH) plays an important role in longitudinal bone growth, and hypophysectomized rats or mutant rats exhibiting dwarfism have generally been used as a GH-deficient model for humans. There also has been a GH deficient model produced by subcutaneous administration to neonatal rats with monosodium glutamate (MSG), followed by destroying GH releasing hormone (GHRH) neurons in the hypothalamic arcuate nucleus, leading to a reduction of GHRH release and a resultant reduction of GH. Recently, Mini rats, a Wistar-derived transgenic rat strain harboring a rat GH antisense gene and showing 40% lower plasma GH levels than Wistar rats, have been developed. In a previous study, Mini rats showed a smaller femur size with lower mineral density and a reduction of the metaphyseal and diaphyseal bone mass. In the present study, neonates of Wistar rats were treated subcutaneously with MSG to obtain GH-deficient rats (MSG rats), and their bones were examined and compared with age-matched MSG-untreated Wistar rats and Mini rats. Compared with the Wistar rats, body weights of the MSG rats were comparable, whereas those of the Mini rats were significantly lower. Bone size, bone mineral content and mineral density were significantly lower in the MSG rats and Mini rats than those in the Wistar rats. Histologically, the amounts of the metaphyseal cancellous bone mass and diaphyseal cortical bone mass were less in the MSG rats and much less in the Mini rats. Compared with the Wistar rats, the growth plate width and longitudinal growth rate were similarly lower. However, there were no differences in bone surface-referent parameters in the secondary spongiosa for histomorphometry among the MSG rats, Wistar rats, and Mini rats, indicating that GH may not influence bone remodeling. Thus, Mini rats are considered to be a useful model for clarifying features of GH-deficiency and examining the effects of various treatments on the bone without any specific surgery or drug administration.

Mini rats have been reported to be a Wistar-derived strain of transgenic rats that harbors a rat growth hormone (GH) antisense gene and shows lower plasma GH levels than Wistar rats. Our previous study has revealed that: 1) Mini rats show smaller hind limbs with lower metaphyseal and diaphyseal bone mass than Wistar rats; 2) that the differences of the diaphyseal cortical bone mass and metaphyseal bone mass between Mini rats and Wistar rats are due largely to the differences in the periosteal bone formation and longitudinal growth rate, respectively, and ; 3) that the bone turnover in the secondary spongiosa, an area were bone remodeling may occur, does not differ between the two strains. In the present study, 8-week-old male Mini rats were treated intraperitoneally with GH at doses of 0, 2, 6 or 20 IU/kg/time twice daily for 14 days. After the dosage period, we measured the size, bone mineral content, and mineral density of the femur and tibia in each group, and we performed cancellous and cortical bone histomorphometry on the tibia to examine the effects of GH on the bone modeling and remodeling. In the GH-treated groups there were increases in the metaphyseal cancellous bone mass, growth plate width, longitudinal growth rate, and periosteal bone formation accompanied by increases in bone size, mineral content, and mineral density in a dose-related fashion. However, bone histomorphometric parameters related to bone turnover in the secondary spongiosa of the metaphysis, where lamellar bone formation took place, did not differ between the control and GH-treated groups. These findings indicated that GH may not influence bone remodeling in the latter groups, and that GH replacement may not influence the number of osteoclasts involved in bone resorption in Mini rats as a whole.

We present here a 78-year-old female patient with acute myeloid leukemia (AML), French-American-British classification M2, exhibiting isodicentric chromosome 21, idic(21)(q22), at the time of diagnosis. The patient had three idic(21)(q22), besides the del(5)(q13q32), add(21)(q22), dic(21;22) (q22; q13), and +22. Fluorescence in situ hybridization studies with whole-chromosome painting and centromere-specific probes for chromosome 21 verified the diagnosis of idic(21)(q22). There were no distinct clinicohematological characteristics of AML with isodicentric 21. The patient was treated with remission-induction therapy followed by consolidation therapy. Two years later, the patient showed the disappearance of isodicentric 21 but retained del(5)(q13q32) and gained other chromosomal abnormalities, +add(17)(p11) and −16. To our knowledge, this is the first report of AML with acquired idic(21)(q22).

Thin films of a superconducting oxide (Nd, Ce)2CuO y , noted as an electron-doped type were prepared on a SrTiO3 (100) substrate by tripolar-type DC magnetron sputtering. Two kind of metals: Nd ‒ Ce alloy and Cu were used as targets to fabricate multimetal films. To make an oxide, two-step oxidation in air was effective, c-axis oriented films were prepared with Tc (onset) = 15 K and a resistivity of 7 m Ω cm, whose value is good enough as an electrode for a ferroelectric thin film.