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A new $\mu$TCA DAQ system was introduced in CANDLES experiment with SpaceWire-to-GigabitEthernet (SpaceWire-GigabitEthernet) network for data readout and Flash Analog-to-Digital Converters (FADCs). With SpaceWire-GigabitEthernet, we can construct a flexible DAQ network with multi-path access to FADCs by using off-the-shelf computers. FADCs are equipped 8 event buffers, which act as de-randomizer to detect sequential decays from the background. SpaceWire-GigabitEthernet has high latency (about 100 $\mu$sec) due to long turnaround time, while GigabitEthernet has high throughput. To reduce dead-time, we developed the DAQ system with 4 "crate-parallel" (modules in crates are read in parallel) reading threads. As a result, the readout time is reduced by 4 times: 40 msec down to 10 msec. With improved performance, it is expected to achieve higher background suppression for CANDLES experiment. Moreover, for energy calibration, "event-parallel" reading process (events are read in parallel) is also introduced to reduce measurement time. With 2 "event-parallel" reading processes, the data rate is increased 2 times., Comment: 21st Real Time Conference (2018), Williamsburg, Virginia, USA. 8 pages, 13 figures, 3 tables, 22 references

We developed a CANDLES-III system to study the neutrino-less double beta (0$\nu\beta\beta$) decay of $^{48}$Ca. The proposed system employs 96 CaF$_{2}$ scintillation crystals (305 kg) with natural Ca ($^{\rm nat.}$Ca) isotope which corresponds 350\,g of $^{48}$Ca. External backgrounds were rejected using a 4$\pi$ active shield of a liquid scintillator surrounding the CaF$_2$ crystals. The internal backgrounds caused by the radioactive impurities within the CaF$_2$ crystals can be reduced effectively through analysis of the signal pulse shape. We analyzed the data obtained in the Kamioka underground for a live-time of 130.4\,days to evaluate the feasibility of the low background measurement with the CANDLES-III detector. Using Monte Carlo simulations, we estimated the background rate from the radioactive impurities in the CaF$_{2}$ crystals and the rate of high energy $\gamma$-rays caused by the (n, $\gamma$) reactions induced by environmental neutrons. The expected background rate was in a good agreement with the measured rate, i.e., approximately 10$^{-3}$ events/keV/yr/(kg of $^{\rm nat.}$Ca), in the 0$\nu\beta\beta$ window. In conclusion, the background candidates were estimated properly by comparing the measured energy spectrum with the background simulations. With this measurement method, we performed the first search for 0$\nu\beta\beta$ decay in a low background condition using a detector with a Ca isotope, in which the Ca present was not enriched, in a scale of hundreds of kg. The $^{48}$Ca isotope has a high potential for use in 0$\nu\beta\beta$ decay search, and is expected to be useful for the development of a next-generation detector for highly sensitive measurements.

High energy γ rays with several MeV produced by (n,γ) reactions can be a trouble for low background measurements in the underground laboratories such as double beta decay experiments. In the CANDLES project, which aimed to observe the neutrino-less double beta decay from 48Ca, γ rays caused by (n,γ) reactions were found to be the most significant background. The profile of the background was studied by measurements with a neutron source and a simulation with a validity check of neutron processes in Geant4. The observed spectrum of γ rays from (n,γ) reactions was well reproduced by the simulated spectra, which were originated from the surrounding rock and a detector tank made of stainless steel. The environmental neutron flux was derived by the observed event rate of γ rays from (n,γ) reactions using the simulation. The thermal and non-thermal neutron flux were found to be ( 1.3 ± 0.6 ) × 10 − 6 cm − 2 s − 1 and ( 1.1 ± 0.5 ) × 10 − 5 cm − 2 s − 1 , respectively. It is necessary to install an additional shield to reduce the background from (n,γ) reaction to the required level.

In a neutrinoless double-beta decay ($0\nu\beta\beta$) experiment, energy resolution is important to distinguish between $0\nu\beta\beta$ and background events. CAlcium fluoride for studies of Neutrino and Dark matters by Low Energy Spectrometer (CANDLES) discerns the $0\nu\beta\beta$ of $^{48}$Ca using a CaF$_2$ scintillator as the detector and source. Photomultiplier tubes (PMTs) collect scintillation photons. At the Q-value of $^{48}$Ca, the current energy resolution (2.6%) exceeds the ideal statistical fluctuation of the number of photoelectrons (1.6%). Because of CaF$_2$'s long decay constant of 1000 ns, a signal integration within 4000 ns is used to calculate the energy. The baseline fluctuation ($\sigma_{baseline}$) is accumulated in the signal integration, thus degrading the energy resolution. This paper studies $\sigma_{baseline}$ in the CANDLES detector, which severely degrades the resolution by 1% at the Q-value of $^{48}$Ca. To avoid $\sigma_{\rm baseline}$, photon counting can be used to obtain the number of photoelectrons in each PMT; however, a significant photoelectron signal overlapping probability in each PMT causes missing photoelectrons in counting and reduces the energy resolution. "Partial photon counting" reduces $\sigma_{baseline}$ and minimizes photoelectron loss. We obtain improved energy resolutions of 4.5-4.0% at 1460.8 keV ($\gamma$-ray of $^{40}$K), and 3.3-2.9% at 2614.5 keV ($\gamma$-ray of $^{208}$Tl). The energy resolution at the Q-value is estimated to be improved from 2.6% to 2.2%, and the detector sensitivity for the $0\nu\beta\beta$ half-life of $^{48}$Ca can be improved by 1.09 times., Comment: This manuscript is prepared for submission to IEEE Transaction on Nuclear Science. It contains 11 pages, 19 figures, and 1 table

The neutrino-less double beta decay (0νββ) is a powerful tool to probe the neutrino mass. The 0νββ is forbidden in Standard Model (SM) due to the violation of lepton number conservation. In experiments searching for 0νββ, the two-neutrino double beta decay (2νββ), which is an allowed process in SM, behaves as an irreducible background within the energy of interest. To discriminate the 0νββ from 2νββ, the energy resolution must be improved. The CANDLES experiment is searching for the 0νββ of 48Ca using CaF 2 (pure) scintillator as the detector and the source. Scintillation photons are collected by Photo Multiplier Tubes (PMTs) surrounding the crystals. A Flash Analog-to-Digital Converter records the waveform of each PMT. Because of the long decay time of CaF 2 (1 µsec), we make a signal integral of 4 µsec to calculate the obtained energy. Thus, the other fluctuation in the baseline is accumulated in the signal integration, and it makes the energy resolution worse. To reduce this fluctuation, we can count the number of photoelectrons in every PMT. Still, we have a significant overlapping probability of single photoelectron signals. This overlapping probability implies the photoelectrons lost, which causes terrible energy resolution. To improve the energy resolution, we introduce an alternative method named "partial photon counting" by dividing the waveform into two parts, then, perform signal integral in the prompt part and photon counting the second part. As a result, the energy resolution is reduced 4.0-3.5 % at 1460 keV (γ-ray of 40K) and 3-2.7 % at 2615 keV (γ-ray of 208Tl).

CANDLES aims to measure the very rare neutrino-less double beta decays using 48Ca which has the highest value among all isotope candidates. Low background techniques are the key to observe such rare phenomena. The largest background was found to be the high energy gamma rays from neutron captures on abundant material near the detector. The shielding system consisted of lead and B-contained rubber sheet was constructed to reduce the background. Performance of the constructed shielding system were described in this paper.

The neutrino-less double beta decay is acquiring great interest after the confirmation of neutrino oscillation which demonstrated nonzero neutrino mass. In order to search for neutrino-less double beta decay of $^{48}$Ca, we proposed the CANDLES project by using CaF$_{2}$(pure) scintillators. Now we installed the CANDLES III system at the Kamioka underground laboratory. The CANDLES III system realizes the low background condition by a characteristic structure and data analyses for background rejection. Furthermore we installed new shielding system in order to reduce $\gamma$-ray backgrounds from neutron capture reaction. Here we report performances of the CANDLES III system.

We have studied the neutrino-less double beta decay(0νββ) of 48Ca by using CaF2(pure) scintillators. Analysis for rejection of backgrounds(212Bi→ 212Po events and 208Tl events) was effective to reduce backgrounds in Qββ-value region. No events are observed in the Qββ-value region for the data of 131 days × 86 kg. It gives a lower limit (90% confidence level) of (math) > 6.2 × 1022 year (preliminary) for the half-life of 0νββ of 48Ca.

The SAMP10 mouse is a model of accelerated ageing in which senescence is characterized by age-related atrophy of the cerebral cortex and limbic structures, poor learning and memory task performance with depressive behaviour and cholinergic and dopaminergic alterations. Here we studied age-related changes in the dendritic arbors and spine density of pyramidal cells in the medial prefrontal cortex of SAMP 10 mice using a quantitative Golgi method. Dendrites of prefrontal neurones gradually retracted with ageing towards the soma with the relative preservation of overall complexity. Apical dendrites were much more severely affected than basal dendrites. The combined length of the apical dendrites and spine density were decreased by 45% and 55%, respectively, in mice at 12 months, compared with mice at 3 months of age. Immunohistochemical and immunoblot analyses indicated that expression of microtubule-associated protein (MAP) 2, a marker of dendrites, decreased in an age-related manner not only in the anterior cortex but also in the posterior cortex and olfactory structures in SAMP10 mice. Decreased expression of MAP2 mRNA caused the decrease in MAP2 protein expression. These results suggest that retraction of apical, but not of basal dendrites, with a loss of spines in prefrontal neurones, appears to be responsible for poor learning and memory performance in aged SAMP 10 mice. It is also suggested that age-related dendritic retraction occurs in a wide area including the entire cerebral cortex and olfactory structures.

The R120G mutation in the small heat shock protein (sHSP) alpha B-crystallin has been identified in a family suffering from desmin-related myopathy. In this study, we characterized the features of transiently expressed R120G alpha B-crystallin in mammalian cells. In addition, we examined interactions of this mutant alpha B-crystallin with Hsp27, another representative sHSP. In HeLa cells, transiently expressed R120G alpha B-crystallin was mainly fractionated in the insoluble fraction, although wild-type alpha B-crystallin was predominantly found in the soluble fraction. In immunofluorescence studies, we found 15-25% of R120G alpha B-crystallin-expressing cells to contain multiple cytosolic inclusion bodies, in which Hsp27 was also localized. When R120G alpha B-crystallin and Hsp27 were transiently co-expressed in HeLa cells, the amount of R120G alpha B-crystallin in the soluble fraction was greater than with expression of R120G alpha B-crystallin alone. Moreover, co-expression resulted in reduced formation of inclusion bodies, suggesting that Hsp27 acts as a molecular chaperone for R120G alpha B-crystallin.

We demonstrated stable midinfrared (MIR) optical frequency comb at the 3.0 μm region with difference frequency generation pumped by a high power, Er-doped, ultrashort pulse fiber laser system. A soliton mode-locked 161 MHz high repetition rate fiber laser using a single wall carbon nanotube was fabricated. The output pulse was amplified in an Er-doped single mode fiber amplifier, and a 1.1–2.2 μm wideband supercontinuum (SC) with an average power of 205 mW was generated in highly nonlinear fiber. The spectrogram of the generated SC was examined both experimentally and numerically. The generated SC was focused into a nonlinear crystal, and stable generation of MIR comb around the 3 μm wavelength region was realized.

The mechanism whereby inorganic carbon (Ci) is acquired by the symbiotic association between the giant clam (Tridacna derasa) and zooxanthellae (Symbiodinium sp.) has been investigated. Ci in the haemolymph of the clam is in equilibrium with the surrounding sea water. The photosynthesis rate exhibited by the intact clam varies as a function of the Ci concentration in the clam haemolymph. The gill tissue contains high carbonic anhydrase activity which may be important in adjusting the Ci equilibrium between haemolymph and sea water. Zooxanthellae (Symbiodinium sp.) isolated from the clam mantle prefer CO2 to HCO 3 - as a source of inorganic carbon. The zooxanthellae have low levels of carbonic anhydrase on the external surface of the cell; however, mantle extracts display high carbonic anhydrase activity. Carbonic anhydrase is absent from the mantle of aposymbiotic clams (T. gigas), indicating that this enzyme may be essential to the symbiosis. The enzyme is probably associated with the zooxanthellae tubes in the mantle. The results indicate that carbonic anhydrase plays an important role in the supply of carbon dioxide within the clam symbiosis.

Efficient power combining of second-harmonic Gunn diodes using an overmoded waveguide resonator has been demonstrated at W-band. In the resonator, a Gunn diode array oscillates at a fundamental frequency and then generates harmonic waves in the common overmoded waveguide resonator. A lamellar backshort has been used to adjust separately the oscillation frequency and the output power. As based on theoretical analyses, the resonator configuration including an output coupling has been optimized. As a result, a combining efficiency of 67% and an output power of 140 mW at 97 GHz have been achieved with three Gunn diodes. The output frequency has been changed from 89.3GHz to 99GHz using the lamellar backshort.

We have proposed Mobile Ethernet (Kuroda, M. et al., IEEE WCNC, 2004) to provide a mobility management mechanism on a widely deployed Ethernet network; it accommodates heterogeneous radio access systems, including 3G. Mobile Ethernet has features to realize fast handover across heterogeneous radio access systems using a mobility management mechanism at layer 2, and to achieve good scalability by partitioning the network in segments to suppress multicast messages. A network processor is a candidate hardware platform for the layer 2 switch which we call Mobile Ethernet switch. We discuss implementation of the switch using the Motorola network processor C-5e/spl trade/ while verifying its feasibility as a Mobile Ethernet switch. We evaluate the switch by the frame forwarding overhead and the number of MAC entries it can support compared to a typical layer 2 switch. We confirm that the Mobile Ethernet switch can forward MAC frames at the line speed of the Gigabit Ethernet by using parallel pipelines in aggregated channel processors in the network processor, though MAC address swapping for interface switching is added to a typical layer 2 switch. The overhead for the additional function is negligible because of the performance limitation of the physical interface in the case of Gigabit Ethernet. We also confirm that the switch can forward frames at gigabit speed by using a hash of more than 14 bits as lookup key for MAC address search, when there are up to 512k MAC entries. This performance and capacity are enough for our Mobile Ethernet assumptions.

In a driver assistant system and a traffic flow monitoring system for ITS, a vision sensor with wide dynamic range is necessary. For imaging target objects under outside environment, dynamic range with 1.5*10/sup 4/ is required, although that of a conventional CCD camera is about 5*10/sup 2/. Our developed sensing system can expand the dynamic range of an image by combining a pair of images successively taken under different exposure conditions. To apply this sensing system to moving objects, a displacement of the target object in a pair of images resulting from motion of the object is evaluated by a normalized correlation method. The experimental results with a miniature car showed the effectiveness of our developed sensing system.

Upper body obesity, related to visceral fat accumulation, is known to increase the risk of various adult diseases, especially type 2 diabetes and cardiovascular disease. This study was conducted to clarify the relationship between upper body obesity and periodontitis. We studied 643 apparently healthy, dentulous Japanese adults who attended programs at Fukuoka Health Promotion Center. Waist-hip ratio, body-mass index (BMI), and body fat were significant risk indicators for periodontitis after adjustment for known risk factors (p < 0.002). Subjects were divided into four BMI (or body fat) categories. In only the subjects with high waist-hip ratio, higher categories of BMI (or body fat) significantly increased the adjusted risk of periodontitis, compared with subjects with low waist-hip ratios and the lowest category of BMI (or body fat). The reported relationship between cardiovascular disease and periodontitis should be reconsidered, since abdominal adiposity or visceral fat can be related to both diseases.

L-arginine is a precursor of nitric oxide (NO) that may be involved in neuronal activity in the gastrointestinal tract. It is known that NO is formed from L-arginine by NO synthase which is localized in neurons in the enteric nervous system. The present study demonstrated that significant L-arginine immunoreactivity was present in the enteric ganglia. Ultrastructural examination showed that L-arginine immunoreactivity was present in the ganglionic glial cells but not in neurons. These findings suggest that enteric glial cells may represent the main reservoir of L-arginine, which may possibly be transferred to neurons when used.

Objective: To describe the relation between body composition and age measured by dual-energy X-ray absorptiometry (DXA) in healthy Japanese adults. Design: Cross-sectional study. Subjects and measurements: The subjects were 2411 healthy Japanese adults (males 625, females 1786, age 20–79 y) who attended the Fukuoka Health Promotion Center, Fukuoka, Japan for health check-up. Body composition was determined by DXA (QDR-2000, Hologic) for the whole body and three anatomical regions of arms, legs and trunk. Results: The mean values of body mass index (BMI) and percentage fat mass (%FM) were 23.2±3.1 (s.d.) kg/m2 and 21.8±6.8% for males and 22.1±3.3 kg/m2 and 32.0±7.5% for females, respectively. For males, curvilinear relations with the peaks in their forties or fifties were seen for the variables associated adiposity, ie BMI, waist and hip circumference, waist–hip ratio, total or regional fat mass (FM), %FM and ratio of trunk FM to leg FM. For females, most of these variables increased linearly in older subjects. Lean mass (LM), bone mineral content (BMC) and bone mineral density (BMD) of the whole body and appendicular LM were relatively constant until the forties and then decreased in both sexes. The rates of decrease in the total or appendicular LM were larger for males than for females, whereas those in BMC or BMD were larger for females than for males. Conclusions: This study presents the first detailed data on body composition in Japanese, which may be useful when comparing with populations of different racial and ethnic backgrounds and studying ill subjects. European Journal of Clinical Nutrition (2001) 55, 462–470

We retrospectively analyzed treatments and outcomes for 83 acute myelogenous leukemia (AML) patients aged 60 years or more (median age 71) admitted to our hospital between August 1984 and January 1998. Complete remission was achieved in 36% of 78 patients who received anti-leukemic therapy, and median overall survival was 227 days. In addition to abnormal karyotypes involving chromosome 5 or 7, administration of less than 120 mg/m2/course of daunorubicin (DNR) during the initial treatment phase was an unfavorable prognostic factor for both CR and survival. Only 41% of all patients received 120 mg/m2/course of DNR or more, and had a significantly higher CR rate (56%) and longer survival, with a median of 389 days. It was suggested that intensive chemotherapy was effective for selected elderly AML patients who were relatively younger and had good performance status, although the number of such patients was limited in our study.

In order to characterize clinical and biological characteristics of elderly patients with acute myelogenous leukemia (AML), we retrospectively analysed 83 elderly patients aged 60 years or more and, as a control, 114 younger patients aged 15 to 59 years who were admitted to our hospital between August 1984 and January 1998. There was a significantly higher incidence of preceding myelodysplastic syndromes in the elderly patients. They also had a significantly higher incidence of unfavorable cytogenetic abnormalities (loss or partial deletion of chromosome 5 or 7) and a significantly lower incidence of favorable cytogenetic abnormalities, such as t(15:17), t(8:21), or inv(16). With regard to FAB subtypes in de novo AML, the incidence of M3 subtype was significantly lower in the elderly group. Myeloperoxidase positivity of AML cells in the elderly group was lower than that in the younger group. Laboratory data at presentation disclosed a lower peripheral leukemic cell count, a higher fibrinogen level, a lower serum protein level, and a higher serum creatinine level in the elderly group. They also had poorer performance status and more frequent concomitant diseases at presentation, including liver diseases, heart diseases, or documented infections. It was concluded that elderly AML patients 60 years or older had a higher incidence of poor prognostic factors compared to younger patients.

Nine dimaltoside derivatives of ethane-1,2-diol, propane-1,3-diol, and butane-1,4-diol having the alpha,alpha, alpha,beta, and beta,beta anomeric configurations at the linkage sites have been synthesized. Suitably protected maltosyl halides or a 1-(phenylthio) derivative were condensed with the foregoing diols and the resulting monomaltosyl derivatives were further condensed with the maltosyl donors to give, after deprotection, the title compounds. Their structures were fully characterized by NMR spectroscopy. Interactions between the three alpha,alpha-(dimaltoside)s and cinnamyl alcohol are briefly discussed.

A 53-year-old man with severe aplastic anemia developed sporadic Vibrio vulnificus septicemia 1 day after eating raw fish and shellfish. Although V. vulnificus infection is potentially fatal, he was saved by immediate and sensitive antibiotic administration. Patients with chronic hematologic disease are susceptible to infection by this organism and are prone to developing septicemia when they eat raw seafood. It is necessary for a patient with this infection to be given effective antibiotics as quickly as possible.

Between October 1990 and April 1996, we treated 892 upper urinary tract stones with ESWL therapy using Lithostar (Siemens Medizinische Technik, Erlangen, Germany). In March 1993, the coupling head of lithotriptor was upgraded from "standard-tube" to "C-tube". The C-tube has approximately two times or more destructive energy and intensity than the standard-tube. In this study, we analyzed the clinical results according to type of coupling head in 713 cases treated by ESWL monotherapy and evaluated 3 months after the initial treatment. The overall success rate at 3 months after ESWL was 85% in the standard-tube cases and 93% in the C-tube cases; the stone-free rate was 72% and 82%, respectively. There were no cases in which had to be discontinued due to ESWL severe side effects. However, in 66.1% of the C-tube cases and 31.1% of the standard-tube cases, a sufficient destructive intensity could not be used because of pain. Within a group that received sufficient destructive intensity, the C-tube was able to reduce both duration of the procedure and the number of shots to two thirds of that of the standard-tube.

We report a case of severe aplastic anemia (SAA) treated with granulocyte colony-stimulating factor (G-CSF), cyclosporin A and danazole, in which myelodysplastic syndrome (MDS) with monosomy 7 developed eight months later. A 24-year-old woman was diagnosed as having SAA and was initially treated with G-CSF, cyclosporin A and danazole. At initial presentation, bone marrow aspirate revealed marked hypocellularity with a normal karyotype (46, XX [20]) and no MDS features. Eight months after initial treatment, leukocytosis and reticulocytosis were observed and bone marrow aspirate showed hypercellular marrow with morphological and cytogenetic features (45, XX, -7 [16]/46, XX [4]) characteristic of MDS (refractory anemia). A total of 75 mg (1.25 mg/kg) of G-CSF had been administered during the preceding eight months. Among seven previous reports published in Japan since 1992, in which MDS/acute myelogenous leukemia (AML) developed from SAA treated with G-CSF, six showed monosomy 7. Careful observation for leukemic transformation is therefore indicated in patients with SAA who are treated with G-CSF.

Recently various cytokines have been introduced into the clinic and have played important therapeutic roles in the treatment of hematological malignancies. Among these cytokines, we have focused on interferon (IFN) and granulocyte (G) or granulocyte-macrophage (GM) colony stimulating factor (CSF), which are currently the most useful cytokines in this review. IFN-a is one of most useful and wide-ranging antitumor agents in hematological malignancies. The most striking effects have been studies in chronic phase CML. Cytogenetic responses are seen in 30-40% of the treated patients, and a complete cytogenetic response can be seen in about 10%. Long-term survival can be expected in these patients. Considering the risk of graft-versus-host disease-associated mortality in allogeneic bone marrow transplantation, the most appropriate category of treatment is difficult to determine in IFN-responsive patients. Elucidation of the antitumor mechanism of IFN, as a prototype for other biological response modifiers, may revolutionize cancer treatment. G- and GM-CSF (CSFs) have reduced the duration of neutropenia, incidence of infectious episodes and days of hospitalization following cancer chemotherapy or stem cell transplantation. CSFs have also been used to mobilize peripheral blood stem cells and to increase the dose intensity of chemotherapeutic agents. Leukemic cells from many patients with acute myelogenous leukemia (AML) have surface receptors for CSFs and may proliferate in response to CSFs. However, several randomized studies showed that CSFs can be used safely and effectively in augmenting neutrophil recovery in patients with AML when given after induction chemotherapy. Various trials have been conducted to sensitize leukemic cells by CSFs, making them more susceptible to chemotherapy; but no convincing evidence has been obtained.

A case of vesical endometriosis associated with unilateral renal agenesis and uterus didelphys (Wunderlich syndrome) is reported. A 20-year-old unmarried woman visited the gynecologic department with dysmenorrhea. She was referred to us because a bladder mass was detected on abdominal ultrasonography. She had no episode of gross hematuria. Cystoscopy revealed a finger tip-sized cystic mass dark red to dark blue in color. Computerized tomography and magnetic resonance imaging demonstrated right renal agenesis and uterus didelphys. The mass was located at the ureterovesical pouch and protruded into the bladder. Partial cystectomy, right hysterectomy and right salpingo-oophorectomy were performed. Histopathological diagnosis was endometriosis. The patient was treated with 400 mg danazol for 6 months has had no recurrence and regular menstruation.

Thirty-two adults (median age 48 years) with acute myelogenous leukemia (excluding M3) have been treated with short-term intensive therapy (M90 therapy). After induction therapy with daunorubicin, cytosine arabinoside (araC), 6-mercaptopurine, prednisolone, mitoxantrone (MIT) and etoposide (VP16), three regimens of post-induction chemotherapy were conducted as short an intercycle time as possible. The first regimen was with MIT and VP16, the second with behenoyl-araC and aclarubicin and the third with VP16, araC, vincristine and vinblastine. No further therapy was given. Complete remission was achieved in 24 (75%) of 32 patients and 24% of all patients were projected to remain free of disease at 5 years. The median duration of the entire therapy was 120 days with a range of 95 to 157 days. Post-induction regimens resulted in severe myelosuppression and their toxicity included treatment-related death in one patient. The treatment results of this short-term therapy were comparable to a former treatment protocol, M84 therapy with a median duration of the entire treatment therapy of 515 days. To confirm the advantages of such short-term therapy, prospective randomized comparisons with conventional post-induction therapy may be required.

A 53-year-old woman was admitted to our hospital in April 1995, because of nasal obstruction, bloody rhinorrhea and hearing disturbance. She had no lymphadenopathy or skin eruptions. Laboratory examinations revealed a WBC count of 2.7 x 10(9)/L without abnormal cells, positive serum anti-HTLV-I antibody, normal lactate dehydrogenase and normal calcium level. MRI showed an epipharyngeal mass. No involvement was detected by CT scanning of the chest and abdomen, 67Ga scintigraphy and bone marrow biopsy. The pathological diagnosis of the biopsied specimen from the epipharyngeal mass was T-cell diffuse lymphoma, pleomorphic type. Monoclonal integration of HTLV-I proviral DNA was detected in lymphoma cells, which confirmed a diagnosis of extranodal adult T-cell leukemia lymphoma primarily involving the epipharynx. She was treated with CAMBO-VIP regimen followed by adjuvant involved-field radiotherapy and she continues to be in complete remission as of April 1996.

In order to analyse the clinical characteristics and outcome in acute myelogenous leukemia, 129 consecutive adult patients admitted to our hospital over a 10-year period, from August 1984 to July 1994, were studied. Their median age was 51 years, 17 (13.2%) of them had antecedent myelodysplastic syndrome (MDS) and 9 (7.0%) had secondary leukemia. Seventy-eight patients (60.5%) were considered eligible for cure-oriented intensive chemotherapy. Forty-four patients were ineligible of one or more of the following; age over 70, antecedent MDS or secondary leukemia. Additional 7 patients were excluded due to concurrent severe diseases. The median survival of the 129 patients was 441 days with an actuarial 5-year survival of 28.6 +/- 4.4%, and the disease-free survival (DFS) decreased with the increasing age of the patient. In 78 patients who were eligible for intensive chemotherapy, complete remission was achieved in 84.6% and overall DFS was 41.1 +/- 5.9% at 5 years, and their survival was longer than that of ineligible patients. It was suggested that considerable selection of patients, for example, due to old age, already existed before visiting our hospital. Analysis of clinical data of unselected patients might enable the development of a rational approach to the management of elderly patients.

Five cases of hereditary high red cell membrane phosphatidylcholine hemolytic anemia in three families were described. All cases were clinically manifested by jaundice and splenomegaly. Hemolysis was evident from indirect hyperbilrubinemia, reticulocytosis and decrement of serum haptoglobin. Red blood cells showed morphological abnormalities such as poikylocytosis, anisocytosis and target cells on blood smears. Both direct and indirect Coombs' tests were negative. Ham test, sugar water test and hemoglobin electrophoresis showed no abnormalities. Osmotic fragility test showed decreased membrane fragility. Lipid analysis of red cell membrane showed increment of phosphatidylcholine content and decrement of sphingomyelin content, although plasma lipids were essentially normal. Influx and efflux of sodium through the red cell membrane were both increased. Splenectomy was performed without effect on one patient and the mother of other patients.

A 44 year-old woman with acute myeloid leukemia (AML, FAB, M4E) developed heart failure during treatment with anthracyclines for AML. She had not experienced heart disease and her left ventricular ejection fraction (LVEF) was 59% at the end of a successful remission induction therapy. Because her LVEF decreased to 33% after early consolidation therapy, the chemotherapy for AML was discontinued. The cumulative dose of daunorubicin, aclarubicin and mitoxantrone was 486 mg/m2, 135 mg/m2 and 55 mg/m2, respectively. In October 1990, four months after the end of the chemotherapy, heart failure (class III, NYHA) developed and did not improve by treatment consisting of dobutamin, digoxin and diuretics. Anthracycline cardiomyopathy was histologically confirmed by endomyocardial biopsy. Then we administered selective beta 1-antagonist, metoprolol (Seloken), with an initial dose of 5 mg/day which was doubled 3 times every 4 or 8 weeks to 40 mg/day, according to the treatment schedule of dilated cardiomyopathy. She recuperated satisfactorily (Class I, NYHA), and was discharged on February '91. Her LVEF gradually improved and it has been maintained at above 50% on an outpatient basis. The patient has been in complete hematological remission during this period. It seems that low dose selective beta 1-antagonist therapy has a potential to improve myocardial function in some patients with anthracycline cardiomyopathy.

A 41-year-old woman with follicular lymphoma developed sporadic respiratory syncytial virus (RSV) pneumonia shortly after allogeneic bone marrow transplantation from an HLA-matched sibling. RSV pneumonia is potentially fatal in immunosuppressed patients, but she improved along with the recovery of bone marrow function without specific treatment. Early recovery of myelosuppression supported by granulocyte colony-stimulating factor may have helped to control RSV pneumonia.

A 49-year-old man with myelodysplastic syndrome (MDS, RAEB in T) who relapsed following allogeneic bone marrow transplantation (allo BMT) was treated with infusions of donor buffy coat leukocytes. He sustained hematologic and cytogenetic remission, but severe graft-versus-host disease (GVHD) developed for which cyclosporin A and prednisolone were required. This therapeutic approach appears to be valuable for relapsed MDS following allo BMT as well as for chronic myelogenous leukemia (CML).

A 42-year-old man diagnosed with von Willebrand disease 7 years earlier visited his home doctor with a chief complaint of gross hematuria. Abdominal ultrasonography showed bilateral renal tumors. He was referred to our hospital on June 15, 1993. His mother also had von Hippel-Lindau disease and was treated by hemodialysis after bilateral nephrectomy. The examination and imaging revealed bilateral renal cell carcinoma of von Hippel-Lindau disease associated with von Willebrand disease. Partial nephrectomy and enucleation for a small tumor on the right side and enucleations for five tumors on the left side were performed. Histological diagnosis of all tumors were renal cell carcinoma, clear cell subtype, grade 1 approximately 2. The patient has been well without local recurrence or distant metastasis for 16 months since the operation. This is the first case of bilateral renal cell carcinoma of von Hippel-Lindau disease associated with von Willebrand disease in Japan.

A 60-year-old man visited our hospital with a chief complaint of penile tumor on November 13, 1984. Circumcision of true phimosis was performed and biopsy of the 27 x 27 mm fixed tumor on the glans revealed well differentiated squamous cell carcinoma. Seventy Gy of electron irradiation to the penis revealed a complete response. On February 1, 1985 bilateral inguinal lymph node dissection was performed and revealed metastasis to a left inguinal node. In May 1990, erosive changes occurred on the irradiated region, and local recurrence was confirmed. Since 2 courses of MBD (methotrexate, bleomycin, cisplatin) chemotherapy was not effective, additional wedge dissection was performed. In January 1992, local recurrence was found. Four courses of intra-arterial chemotherapy (cisplatin, vincristine, methotrexate, adriamycin) was performed with a complete response. No evidence of disease has been recognized for more than two years after completion of the treatment.

SRPX2 (Sushi repeat-containing protein, X-linked 2) has recently emerged as a multifunctional protein that is involved in seizure disorders, angiogenesis and cellular adhesion. Here, we analyzed this protein biochemically. SRPX2 protein was secreted with a highly post-translational modification. Chondroitinase ABC treatment completely decreased the molecular mass of purified SRPX2 protein to its predicted size, whereas heparitinase, keratanase and hyaluroinidase did not. Secreted SRPX2 protein was also detected using an anti-chondroitin sulfate antibody. These results indicate that SRPX2 is a novel chondroitin sulfate proteoglycan (CSPG). Furthermore, a binding assay revealed that hepatocyte growth factor dose-dependently binds to SRPX2 protein, and a ligand–glycosaminoglycans interaction was speculated to be likely in proteoglycans. Regarding its molecular architecture, SRPX2 has sushi repeat modules similar to four other CSPGs/lecticans; however, the molecular architecture of SRPX2 seems to be quite different from that of the lecticans. Taken together, we found that SRPX2 is a novel CSPG that is overexpressed in gastrointestinal cancer cells. Our findings provide key glycobiological insight into SRPX2 in cancer cells and demonstrate that SRPX2 is a new member of the cancer-related proteoglycan family.

We evaluated 59 patients with voiding dysfunction after abdominal radical hysterectomy for uterine cancer. Of 59 patients, 45 underwent the surgery alone, and the other 14 underwent surgery and postoperative radiotherapy. Irradiation (mean dose, 60 Gy) was performed in bilateral commoni iliac regions excluding the bladder. In principle, the indwelling urethral catheter was removed 4 days after operation. All patients were followed up at the gynecological department until the onset of the voiding dysfunction. The mean interval between operation and the onset of voiding dysfunction was significantly longer (P0.01) in the group treated by surgery alone (7.9 years) than in the group treated by surgery in combination with radiotherapy (3.8 years). Voiding dysfunction developed earlier as the age at the time of operation was higher. No differences were observed in the volume of residual urine, the detrusor function, or the incidence of urinary tract infection between the two groups. These results suggest that aged patients develop voiding dysfunction earlier after radical hysterectomy than young patients, and postoperative radiotherapy shortens the interval between operation and the onset of postoperative voiding dysfunction.

We present a case report of a relapse to the mediastinal lymph node alone, 38 months after orchiectomy on surveillance for stage I typical seminoma. The patient, a 63-year-old man, was treated with high inguinal orchiectomy for left testicular tumor and close follow-up. After 38 months from the initial treatment, the chest X-ray film and CT scan revealed mediastinal tumor. Fine needle aspiration cytology performed under the bronchoscopy showed seminoma cells. Complete remission was achieved after three courses chemotherapy of cisplatin, vincristine, methotrexate, peplomycin and etoposide (COMPE). He has continued to be clinically disease-free 8 months after completion of the treatment. According to the available data in the literature, 94% of the recurrences was detected within 3 years after orchiectomy, and 92% involved retroperitoneal lymph node metastases. This is a rare case who had a late relapse in the mediastinum alone.

In Escherichia coli, expression of the major outer membrane proteins, OmpC and OmpF, is regulated through the functions of OmpR and EnvZ at the transcriptional level in response to the medium osmolarity. OmpR is the crucial activator that helps RNA polymerase to efficiently trigger ompC and ompF transcription. This OmpR function is modulated by phosphorylation mediated by the cognate sensory kinase, EnvZ. Phosphorylation at the N-terminal domain of OmpR results in substantial enhancement of the DNA-binding ability of the C-terminal domain, thereby allowing the activation of ompC and ompF transcription by OmpR. Here we isolated an OmpR mutant which lacks the N-terminal half, but can enhance transcription in vivo. This novel type of OmpR mutant was revealed to have a single amino acid replacement of Gly227 to Cys. The newly-introduced-Cys residue allows OmpR molecules to form a stable dimer in vitro without the help of the N-terminal half. This altered C-terminal half is able to bind efficiently and specifically to the cognate DNA in vitro. It can function as an activator for ompC transcription in vitro in a phosphorylation-independent manner. These results suggest that the putative activator domain of OmpR, together with the DNA-binding domain, is most likely located in the C-terminal half. They also suggested that the phosphorylation of OmpR may not be essential for gene activation per se.

We investigated the expression of P-glycoprotein (P-gp) in 52 adults with de novo acute myelogenous leukemia (AML) at the initial diagnosis. We tested 52 patients by flow cytometry using the MRK16 monoclonal antibody (MoAb). To investigate the phenotype for multidrug resistance, 41 of the patients were analyzed using rhodamine 123 (Rh123). We found that 14 (27%) of the 52 patients were positive for P-gp expression by MRK16 MoAb using a cutoff of 5% positive cells. There was a significant correlation between the results of the two analyses (p0.01). We suggest that flow cytometry using MRK16 MoAb is acceptable for use in detecting P-gp expression in clinical samples. Among the 52 patients, 43 (83%) obtained a complete remission (CR) and 45% of remitters were predicted to be alive and in a CR after 8 years. Although the rate of CR on the MRK16-positive patients was comparable to that of the MRK16-negative patients, the MRK16-positive patients were prone to relapse. We conclude that determination of P-gp expression of de novo AML at initial presentation did not significantly influence the outcome of treatment.