Koji Obata

Discrimination of Nonobstructive Hypertrophic Cardiomyopathy From Hypertensive Left Ventricular Hypertrophy on the Basis of Strain Rate Imaging by Tissue Doppler Ultrasonography

Background—The differentiation of hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) on the basis of morphological information obtained by conventional echocardiography is occasionally problematic. We investigated whether strain rate (SR) imaging derived from tissue Doppler imaging (TDI) is able to discriminate HCM from H-LVH. Methods and Results—Conventional echocardiography and TDI were performed with 34 patients with LVH and 16 reference subjects. Mean values of systolic strain (&egr;sys), peak systolic SR, and early diastolic SR obtained from 8 left ventricular (LV) segments were calculated. LV pressures were recorded simultaneously in the patients. Patients were diagnosed with HCM (n=20) or H-LVH (n=14) on the basis of conventional echocardiography and endomyocardial biopsy findings. Multivariate analysis revealed that septum/posterior wall thickness ratio (P=0.00013) and &egr;sys (P<0.0001) were each able to discriminate HCM from H-LVH. A &egr;sys cutoff value of −10.6% discriminated between HCM and H-LVH with a sensitivity of 85.0%, specificity of 100.0%, and predictive accuracy of 91.2%. The combination of the septum/posterior wall thickness ratio and &egr;sys discriminated HCM from H-LVH with a predictive accuracy of 96.1%. The &egr;sys parameter was significantly correlated with pulmonary arterial wedge pressure, LV end-diastolic pressure, the peak positive first derivative of LV pressure, and the time constant of LV pressure decay. Conclusions—SR imaging is able to discriminate HCM from H-LVH, with &egr;sys reflecting myocardial contractile and lusitropic properties.

Attenuation of ventricular hypertrophy and fibrosis in rats by pitavastatin: potential role of the RhoA-extracellular signal-regulated kinase-serum response factor signalling pathway.

1 Inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (statins) manifest pleiotropic effects that may contribute to their therapeutic efficacy. However, the mechanism of the beneficial action of statins on cardiac hypertrophy and fibrosis remains unclear. We have now investigated this action of pitavastatin in Dahl salt‐sensitive (DS) rats. 2 The DS rats progressively develop marked hypertension when fed a diet containing 8% NaCl from 7 weeks of age. These animals exhibited pronounced cardiac hypertrophy and fibrosis, as well as upregulation of fetal‐type cardiac gene expression at 12 weeks of age, compared with DS rats fed a diet containing 0.3% NaCl. The abundance of mRNAs for collagen types I and III, angiotensin‐converting enzyme, transforming growth factor‐β1 and connective tissue growth factor was also increased in the heart of rats on the high‐salt diet. 3 Treatment of rats on the high‐salt diet with a non‐antihypertensive dose of pitavastatin (0.3 or 1 mg/kg per day) from 7 to 12 weeks of age attenuated the development of cardiac hypertrophy and fibrosis, as well as inhibiting the upregulation of cardiac gene expression. Pitavastatin also blocked the translocation of RhoA to the membrane fraction of the left ventricle and RhoA activation, as well as the phosphorylation of the mitogen‐activated protein kinases extracellular signal‐regulated kinase (ERK)‐1 and ERK‐2 and an increase in the DNA binding activity of serum response factor (SRF) in the heart induced by the high‐salt diet. 4 These findings suggest that the effects of pitavastatin on load‐induced cardiac hypertrophy and fibrosis are independent of its cholesterol‐lowering action and may be mediated, at least in part, through inhibition of RhoA–ERK–SRF signalling.

Design, Implementation and On-Chip High-Speed Test of SFQ Half-Precision Floating-Point Multiplier

We are developing a large-scale reconfigurable data path (LSRDP) using single-flux-quantum (SFQ) circuits as a fundamental technology that can overcome the power-consumption and memory-wall problems in CMOS microprocessors in future high-end computing systems. An SFQ LSRDP is composed of several thousands of SFQ floating-point units connected by reconfigurable SFQ network switches to achieve high performance with low power consumption. In this study, we designed and implemented an SFQ floating-point multiplier (FPM), which is one of the key components of the SFQ LSRDP. We designed a systolic-array bit-serial half-precision FPM using the 2.5 kA/cm2 Nb process. The resultant circuit area and number of Josephson junctions are 6.22 mm times 3.78 mm and 11044, respectively. The designed clock frequency is 25 GHz. We tested the circuit and confirmed the correct operation of the FPM by on-chip high-speed tests.

Design and Implementation and On-Chip High-Speed Test of SFQ Half-Precision Floating-Point Adders

We are developing a large-scale reconfigurable data-path (LSRDP) based on single-flux-quantum (SFQ) circuits to establish a fundamental technology for future high-performance computing systems. In the LSRDP, an SFQ floating-point adder (FPA) is one of the main and most complicated circuit blocks. In this paper, we designed and implemented an SFQ half-precision FPA and carried out on-chip high-speed tests. The data format of the half-precision FPA obeys the IEEE standard, in which two input data streams, an 11-bit significand and a 6-bit sign/exponent, are processed bit-serially. The floating-point addition is performed by three steps: (1) alignment and rounding of significands, (2) addition/subtraction of the significands, and (3) normalization of the result. We implemented an SFQ half-precision FPA using the SRL 2.5 kA/cm2 niobium standard process. The size, power consumption and total junction number are 5.86 mm times 5.72 mm, 3.5 mW and 10224, respectively. The simulated DC bias margin is plusmn20% at 20 GHz operation, which corresponds to the performance of 1 GFLOPS. We successfully confirmed the correct operation of the FPA except a read-out circuit for the significand at 24 GHz by on-chip high-speed tests.

Advanced design approaches for SFQ logic circuits based on the binary decision diagram

We have been investigating a design methodology of SFQ logic circuits based on the binary decision diagram (BDD). In the previously proposed BDD SFQ logic circuits, we have used one-to-two binary switches as a node cell in a BDD tree. In this study we will propose a new implementation method of SFQ BDD circuits, in which two nodes are implemented by using a 2-input 2-output switch gate. By employing the new approach, we have designed and implemented a one-bit full adder using the NEC 2.5 kA/cm/sup 2/ Nb standard process and the CONNECT cell library. The maximum operating frequency of the full adder was found to be 40 GHz by circuit simulations and 32.8 GHz by on-chip high-speed tests.

Increased Levels of Calbindin-D in Serum and Urine from Patients Treated by Extracorporeal Shock Wave Lithotripsy

Calbindin-D 28 kDa. is a vitamin D-dependent calcium binding protein that is found mainly in the distal renal tubules and central nervous tissue in humans. Calbindin-D was measured in the serum and urine before, and immediately, 2 hours or 24 hours after extracorporeal shock wave lithotripsy (ESWL*) in 83 consecutive patients. ESWL was performed with the Siemens Lithostar device in 61 patients and with the Dornier MPL9000 lithotriptor in 22. The serum 28 kDa. calbindin-D level was undetectable (less than 20 pg./ml.) in many samples, whereas urinary 28 kDa. calbindin-D could be detected in every sample. The serum 28 kDa. calbindin-D level was usually elevated after ESWL and the concentration in patients treated with the MPL9000 device was greater than in those treated with the Lithostar instrument. Urinary 28 kDa. calbindin-D levels were elevated significantly immediately and at 2 hours after ESWL, and they decreased to the baseline level within 24 hours after ESWL in the Lithostar group but remained consistently significantly elevated after ESWL in the MPL9000 group. This fact may be because the MPL9000 lithotriptor produces a stronger shock wave than does the Lithostar device during ESWL. These results suggest that 28 kDa. calbindin-D is released from damaged distal renal tubule cells into the serum and urine during ESWL and that 28 kDa. calbindin-D is a specific marker for renal damage by ESWL. To our knowledge this is the first clinical study using a sensitive enzyme immunoassay for human 28 kDa. calbindin-D to estimate renal damage during ESWL.

Primary adenocarcinoma of the renal pelvis with special reference to histochemical observations

A case of adenocarcinoma of the renal peivis is presented. The patient was an 84‐year‐old man suffering from longstanding right‐sided nephrolithiasis. Surgical resection of the right kidney revealed adenocarcinoma with slight stromal invasion. A tubulovillous adenoma, which was morphologically similar to an adenoma of the large Intestine, was also found adjacent to the adenocarcinoma. The pelvic epithelium neighboring the lesion revealed Intestinal metaplasla. Histochemical studies revealed that the tumor In the patient and adenocarcinomas or adenomas of the large intestine have similar properties of cytoplasmic mucin. These findings suggest that the epithelium with intestinal metaplasia may have developed into the adenoma and flnally transformed into the adenocarclnoma. In addition, only tumor cells with severe atypia, most of which morphologically corresponded to adenocarcinoma, demonstrated positive nuclear staining for anti‐p53. This suggests that p53 may play an important role In the malignant transformation of adenomas into adenocarcinomas, as is the case in the large intestine.

Results of adjuvant chemotherapy for invasive urothelial cancer with lymph-node metastasis

From 1980 to 1991, 59 patients with advanced urothelial cancer (pathological stage, >pT3) underwent radical operations. Of these 59 patients, 33 had nodal involvement. This study focused on those 33 patients with nodal involvement. The primary site was the urinary bladder in 20 patients and the upper urinary tract (renal pelvis and/or ureter) in 13. In all, 13 patients underwent adjuvant chemotherapy with an M-VAC or M-VEC [methotrexate (M), vinblastine, doxorubicin (ADM) or epirubicin, and cisplatin (CDDP)] regimen, and another 8 patients were treated with other insufficient chemotherapies [CDDP+ADM or CDDP+ADM_etoposide (VP-16)]. A group of 12 patients did not receive any additional treatment. Most of the patients in the M-VAC and M-VEC groups received more than 2 cycles of the regimen (median, 3.2 cycles; range, 1–9 cycles). The overall 5-year survival rate of the M-VAC and M-VEC group was 31%, whereas the rate was 0 for the other insufficient-chemotherapy groups and the no-chemotherapy group. Of the 13 patients in the M-VAC group, 4 (31%) patients were alive without disease progression and 9 (69%) were dead due to progressive disease. In the other groups, only I patient was alive without progression. Our results suggest that adjuvant M-VAC or M-VEC chemotherapy may extend the median survival of patients with advanced urothelial cancer, but it failed to reduce the rate of cancer death.

Logic Synthesis Method for Dual-Rail RSFQ Digital Circuits Using Root-Shared Binary Decision Diagrams

We propose a new method of logic synthesis for dual-rail RSFQ (rapid single-flux-quantum) digital circuits. RSFQ circuit technology is one of the strongest candidates for the next generation technology of digital circuits. For representing logic functions, we use a root-shared binary decision diagram (RSBDD) which is a directed acyclic graph constructed from binary decision diagrams. In the method, first we construct an RSBDD from given logic functions, and then reduce the number of nodes in the constructed RSBDD by variable re-ordering. Finally, we synthesize a dual-rail RSFQ circuit from the reduced RSBDD. We have implemented the method and have synthesized benchmark circuits. We have synthesized dual-rail circuits that consist of about 27% fewer logic elements than those synthesized by a Transduction-based method on average.

Prophylactic chemotherapy with intravesical instillation of Adriamycin and oral administration of 5-fluorouracil after surgery for superficial bladder cancer

The Japanese Urological Cancer Research Group for Adriamycin has conducted a series of clinical trials to investigate the efficacy and safety of prophylactic intravesical chemotherapy for superficial bladder cancer. In the third trial, reported herein, patients with recurrent bladder cancer or multiple primary cancer were selected and randomized to one of four groups using the envelope method after complete resection of the original tumors. Group A was given Adriamycin alone, group B received oral 5-fluorouracil (5-FU), group C was given Adriamycin and oral 5-FU, and group D served as the control group. Of the 544 patients registered, 331 were evaluable for the purpose of this study. The administration of 5-FU (group B) failed to prevent the recurrence of bladder tumors. Although group C (both Adriamycin and 5-FU) did not fare better than group A (Adriamycin only), Adriamycin was effective in preventing the recurrence of tumors, especially in high-risk patients with recurrent and multiple tumors. The risk of recurrence was reduced to 0.21 (95% confidence interval, 0.10–0.44) relative to the control group. There was no indication of a synergistic effect between 5-FU and Adriamycin. As side effects, cystitis syndrome was observed in 23%–30% of the patients in the Adriamycin groups and mild myelosuppression was observed in the 5-FU groups.