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Objectives As heart failure with concomitant sarcopenia has a poor prognosis, simple methods for evaluating the appendicular skeletal muscle mass index (ASMI) are required. Recently, a model incorporating anthropometric data and the sarcopenia index, that is, the ratio of serum creatinine to cystatin C (Cre/CysC), was developed to estimate the appendicular skeletal muscle mass. We hypothesized that this model would be superior to the previous model, which uses only anthropometric data to predict the prognosis. This study aimed to compare the prognostic value of low ASMI as defined by the biomarker and anthropometric models in patients with heart failure. Methods Among 847 patients, we estimated ASMI using an anthropometric model consisting of age, body weight, and height in 791 patients and a biomarker model that incorporates age, body weight, hemoglobin, and Cre/CysC in 562 patients. Patients were divided into low and non-low ASMI groups according to the ASMI estimated by each model, using the cut-off proposed by the Asian Working Group for Sarcopenia. The primary outcome was all-cause mortality. Results Overall, 53.4% and 39.1% of patients were diagnosed with low ASMI by anthropometric and biomarker models, respectively. The agreement of the diagnosis of low ASMI between the two models was poor, with a kappa coefficient of 0.56 (95% confidence interval: 0.49–0.63). Kaplan-Meier curves showed that a low ASMI was significantly associated with all-cause death in both models. However, this association was retained after adjustment for other covariates in the biomarker model (hazard ratio: 2.60, p=0.003), but not in the anthropometric model (hazard ratio: 0.70, p=0.257). Conclusions and implications Among patients hospitalized with heart failure, a low ASMI estimated using the biomarker model, but not the anthropometric model, was significantly associated with all-cause mortality. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Agency for Medical Research and Development

We have investigated the temperature- and field-variation of electronic state for the Dirac semimetal of ${\mathrm{EuMnBi}}_{2}$ by means of optical spectroscopy and theoretical calculation. The optical conductivity spectra show a clear Drude peak in the paramagnetic phase, which gradually diminishes in the Mn-$3d$ antiferromagnetic phase with decreasing temperature. Meanwhile, the absorption peaks due to the interband transition grow at low temperatures, resulting in a pseudogap feature with an energy scale of 0.07 eV. The analysis of Drude weight shows that the Drude response is nearly governed by the Dirac electrons at low temperatures. On the contrary, both the antiferromagnetic transition and spin reorientation of Eu-$4f$ moment do not significantly change the spectra except the moderate variation of Drude weight. As a comparison, we have also investigated the charge dynamics for ${\mathrm{EuZnBi}}_{2}$, which is an analog without the Mn-$3d$ antiferromagnetic ordering. In ${\mathrm{EuZnBi}}_{2}$, the optical conductivity spectra do not show the pseudogap structure, but show an intense Drude peak at all temperatures. Combined with the results of ab initio calculation, in ${\mathrm{EuMnBi}}_{2}$, it is likely that the reconstruction of electronic state driven by the Mn-$3d$ antiferromagnetic ordering causes the Dirac semimetallic state with tiny hole pockets, wherein electronic states other than the Dirac band are nearly gapped-out from the Fermi level.

Cu2OSeO3 is known as a unique example of insulating multiferroic compounds with skyrmion spin texture, which is characterized by the chiral cubic crystal structure at ambient pressure. Recently, it has been reported that this compound shows pressure-induced structural transition with large enhancement of magnetic ordering temperature Tc. In the present study, we have investigated the detailed crystal structure in the high pressure phase, by combining the synchrotron X-ray diffraction experiment with the diamond anvil cell and the analysis based on the genetic algorithm. Our results suggest that the original pyrochlore Cu network is sustained even after the structural transition, while the orientation of SeO3 molecule as well as the position of oxygen in the middle of Cu tetrahedra are significantly modified. The latter features may be the key for the reported enhancement of Tc and associated stabilization of skyrmion phase at room temperature., 13 pages, 4 figures, 1 table

Here, the authors predict the stability of oxygen-deficient perovskite structures in cuprates by density functional theory calculations. They introduce a combination of cluster expansion, Gaussian process, and Bayesian optimization to find stable oxygen-deficient structures. The calculations not only reproduce the reported structures but suggest the presence of unknown oxygen-deficient perovskite structures, some of which are stabilized at high pressures. This work demonstrates the great applicability of the present computational procedure for the elucidation of the structural stability of strongly correlated oxides.

We report the polarization rotation of terahertz light resonant with the magnetoelectric (ME) spin excitation in the multiferroic (Fe,Zn)_{2}Mo_{3}O_{8}. This resonance reflects the frequency dispersion of the diagonal ME susceptibility (axion term), with which we quantitatively reproduce the thermal and magnetic-field evolution of the observed polarization rotation spectra. The application of the sum rule on the extrapolated dc value of the spectral weight of the ME oscillator provides insight into the dc linear ME effect. The present finding highlights a novel optical functionality of spin excitations in multiferroics that originates from diagonal ME coupling.

The correlation between magnetic and dielectric properties has been investigated for the single crystal of the chiral triangular-lattice helimagnet MnSb_{2}O_{6}. We found that the spin-spiral plane in the ground state has a considerable tilting from the (110) plane and that the sign of the spin-spiral tilting angle is coupled to the clockwise or counterclockwise manner of spin rotation and accordingly to the sign of magnetically induced electric polarization. This leads to unique magnetoelectric responses such as the magnetic-field-induced selection of a single ferroelectric domain as well as the reversal of electric polarization just by a slight tilting of the magnetic field direction, where the chiral nature of the crystal structure plays a crucial role through the coupling of the chirality between the crystal and magnetic structures. Our results demonstrate that crystallographic chirality can be an abundant source of novel magnetoelectric functions with coupled internal degrees of freedom.

Using resonant soft-x-ray scattering as a function of both temperature and magnetic field, we reveal a large number of almost degenerate magnetic orders in SrCo6O11. The Ising-like spins in this frustrated material in fact exhibit a so-called magnetic devil's staircase. It is demonstrated how a magnetic field induces transitions between different microscopic spin configurations, which is responsible for the magnetoresistance of SrCo6O11. This material therefore constitutes a unique combination of a magnetic devil's staircase and spin-valve effects, yielding a novel type of magnetoresistance system.

To investigate the clinical utility of fluorescence in situ hybridization (FISH) of voided urine in the detection of bladder cancer and the prediction of its recurrence.FISH with centromere-specific probes for chromosomes 9 and 17 was performed to evaluate the chromosomal alterations of exfoliated urothelial cells in voided urine obtained from 44 patients with bladder cancer and 20 controls. The analysis was also performed in 17 patients with bladder cancer after complete transurethral resection to prospectively determine whether FISH can predict tumor recurrence.The sensitivity to detect bladder cancer by FISH analysis (85%) was significantly higher than that by urine cytologic examination (32%) and by the bladder tumor antigen test (64%) (P0.0001 and P = 0.026, respectively). The specificity of FISH, cytologic analysis, and the bladder tumor antigen test was 95%, 100%, and 80%, respectively. Among the 17 patients tested after transurethral resection, 7 of 13 FISH-positive patients developed tumor recurrence within the 27-month follow-up period; none of 4 FISH-negative patients developed recurrence during the same period. The recurrence rate in patients with the loss of chromosome 17 was 100%, significantly higher than the 23% for patients without this alteration (P = 0.015).These findings suggest that FISH analysis of exfoliated urothelial cells in voided urine can efficiently detect bladder cancer and predict its recurrence.

We have spectroscopically investigated the thermally and doping-induced metal-insulator transitions for pyrochlore-type Nd2Ir2O7 as well as its Rh-doped analogs Nd2(Ir(1-x)Rh(x))(2)O(7), where the spin-orbit interaction as well as the electron correlation is effectively tuned by the doping level (x). The charge dynamics dramatically changes on an energy scale of 1 eV in the course of thermally and doping-induced metal-insulator transitions, while the insulating ground state shows a small but well-defined charge gap of 45 meV. Anomalous doping variation of the low-energy (0.3 eV) optical-conductivity spectra at the ground state can be interpreted in terms of the phase changes among the narrow-gap Mott insulator, Weyl semimetal, and correlated metal.

Single phase TiO2:Sm3+ thin films (anatase: A‐ or rutile: R‐) have been fabricated on Si substrates by laser ablation with controlled O2 pressure during film preparation. Visible photoluminescence (PL) originating from the intra‐4f transitions in Sm3+ ions were observed at room temperature. The A‐TiO2:Sm3+ thin films exhibited more intense Sm3+‐related PL than that of R‐TiO2:Sm3+, resulting from the difference of Sm3+ configuration in the host crystal matrixes. A phase transition from anatase to rutile of the host changed the local crystal symmetry of the Sm3+ ions and extinguished the Sm3+‐related PL, even there was no significant change on the Sm concentration.

To clarify the microscopic origin of the gigantic magnetoelectric effect in multiferroics, we have investigated the variation of an electric polarization (P) vector under a rotating magnetic field (H) for a cycloidal helimagnet Eu0.55Y0.45MnO3 as a canonical example. P rotates smoothly by rotating H around the magnetic propagation wave vector k, which can be well understood by the rotation of the conical spin structure around k. We also show that the rotation process of the conical spin structure under H is crucial for the retention or reversal of the spin helicity or equivalently of the direction of P.

Fungal endocarditis caused by Candida species is associated with high morbidity and mortality. A combination of surgical resection and antifungal drug therapy is the golden standard for treatment. We reported a case of fungal endocarditis due to Candida lusitaniae found at onset of lower limb acute aortic occlusion cured by emergency operation. This case suggests that Candida endocariditis can be managed medically with antifungal drug therapy in life time.

A two-staged, uniaxial magnetoresistive effect has been discovered in SrCo6O11 having a layered hexagonal structure. Conduction electrons and localized Ising spins are in different sublattices but their interpenetration makes the conduction electrons sensitively pick up the stepwise field dependence of magnetization. The stepwise field dependence suggests two competitive interlayer interactions between ferromagnetic Ising-spin layers, i.e., a ferromagnetic nearest-layer interaction and an antiferromagnetic next-nearest-layer interaction. This oxide offers a unique opportunity to study nontrivial interplay between conduction electrons and Ising spins, the coupling of which can be finely controlled by a magnetic field of a few Tesla.

This paper is concerned with the high reliability of FC-PBGA (Flip Chip-Plastic Ball Grid Array). While flip chip technology is experienced in watch assembly and has a cost advantage, the chip sizes for watches are too small and not directly applicable to high reliable FC-PBGA. Considering the application of FC technology to FC-PBGA, the bump structure change for lower stress will be effective. For this change, three steps have been under examination: (1) application of FC assembly to peripheral bump structure, (2) establishment of re-distribution structure on chip, and (3) application of FC technology to area array bump structure. The result of the first step, application of FC assembly to peripheral bumping is reported in this paper. The bump structure has ensured a thermal fatigue resistance 3,000 cycles under the condition -40 C 30 min/125 C 30 min.

This MPEG2 video decoder LSI decodes MPEG2 standard bit streams. The compression algorithm in the MPEG2 is based on discrete cosine transform (DCT), variable length coding, and motion compensation similar to the MPEG1, the earlier standard. However, the processing speed should be more than four times faster than MPEG1. Moreover, several algorithms and structures to handle interlaced pictures are added to the MPEG1 standard. This LSI decodes in real time all motion-compensation modes and picture structures in MPEG2 bit streams of not only CCIR601 but also HDTV resolution. >

One of the most intriguing developments in recent years towards prevention of restenosis after angioplasty is the use of ionizing radiation. The background for the use of radiation treatment for this application is sound, since radiation is used not only to treat malignant cancerous growths but also is used for treatment of benign hyperplastic disorders such as post-surgical keloid formation and recurrence of pterygium after surgical removal. Restenosis can be considered a form of overexuberant wound healing triggered by angioplasty. Ionizing radiation inhibits serum-stimulated proliferation of many cell types including fibroblasts and smooth muscle cells in vitro and also suppresses the synthesis of collagen by cultured fibroblasts. Liermann who showed inhibition of post-stent restenosis first used ionizing radiation for restenosis prevention clinically in iliac and iliofemoral arteries. Subsequently, extensive animal studies in various restenosis models have shown a profound inhibitory effect of catheter-based radiation (endovascular brachytherapy) on neointima formation and overall vessel shrinkage (negative remodeling). Based on these results clinical trials have been initiated with several types of devices and isotopes. Among these are 192Ir, 32P, 90Y, 90Sr/Y and 188Re. Additionally, radioactive stents have been developed; devices for clinical use are made radioactive at the microCi level by surface implantation of 32P ions. Results from early clinical trials are encouraging and brachytherapy appears safe for clinical use and at an appropriate dose, may be highly effective for restenosis prevention.

A 60-year-old man was admitted to our hospital with the chief complaint of a left upper abdominal mass. 131I-MIBG scintiscan revealed a left upper abdominal mass, and the patient's serum catecholamine level was very high. Our diagnosis was pheochromocytoma of the left adrenal gland. On Oct. 19, 1995, a left nephrectomy and adrenectomy were performed. The serum catecholamine level then decreased and blood pressure was normalized. Two years later, it became difficult to control the patient's hypertension, and multiple metastatic liver cancer was found by an abdominal CT scan. The diagnosis of malignant pheochromocytoma was confirmed by the accumulation of 131I-MIBG in the liver. We started CVD chemotherapy. After 10 cycles of this chemotherapy, the serum catecholamine level was almost normalized and the metastatic liver cancer was reduced to one-third in size.

We investigated the regulatory roles of MgADP and free Ca2+ in isometric tension development in skinned bovine cardiac muscle. We found that, in the relaxed state without free Ca2+, MgADP elicited a sigmoidal increase in active tension, as is the case in skeletal muscle (ADP-contraction). The critical MgADP concentration, at which the tension increment became half-maximal, increased in proportion to MgATP concentration, with a slope of approximately 1 for cardiac and 4 for skeletal muscle. Raising the free Ca2+ concentration decreased the critical MgADP concentration in proportion to the free Ca2+ concentration. In addition, the apparent Ca2+ sensitivity of tension development increased with MgADP, while decreasing with inorganic phosphate (Pi); MgADP suppressed the Ca(2+)-desensitizing effect of Pi in a concentration-dependent manner. These activating effects of MgADP were quantitatively assessed by means of a model based upon the kinetic scheme of actomyosin ATPase. These experimental results and model simulation suggest that the state of thin filaments is synergistically regulated by both the binding of Ca2+ to troponin and the formation of the actomyosin-ADP complex.

Selective removal and reconstitution of the components of muscle fibers (fibrils) is a useful means of examining the molecular mechanism underlying the formation of the contractile apparatus. In addition, this approach is powerful for examining the structure-function relationship of a specific component of the contractile system. In previous studies, we have achieved the partial structural and functional reconstitution of thin filaments in the skeletal contractile apparatus and full reconstitution in the cardiac contractile apparatus. First, all thin filaments other than short fragments at the Z line were removed by treatment with plasma gelsolin, an actin filament-severing protein. Under these conditions, no active tension could be generated. By incorporating exogenous actin into these thin filament-free fibers, actin filaments were reconstituted by polymerization on the short actin fragments remaining at the Z line, and active tension, which was insensitive to Ca2+, was restored. The active tension after the reconstitution of thin filaments reached as high as 30% of the original level in skeletal muscle, while it reached 140% in cardiac muscle. The augmentation of tension in cardiac muscle is mainly attributable to the elongation of reconstituted filaments, longer than the average length of thin filaments in an intact muscle. These results indicate that a muscle contractile apparatus with a high order structure and function can be constructed by the self-assembly of constituent proteins. Recently, we applied this reconstitution system to the study of the mechanism of spontaneous oscillatory contraction (SPOC) in thin (actin) filament-reconstituted cardiac muscle fibers. As a result, we found that SPOC occurs even in regulatory protein-free actin filament-reconstituted fibers (FujitaIshiwata, manuscript submitted), although the SPOC conditions were slightly different from the standard SPOC conditions. This result strongly suggests that spontaneous oscillation is intrinsic to actomyosin motors. We here summarize the contractile properties of the reconstitution system.

The relationship between the evolution of ischemic heart disease and changes in lipid profile was investigated in 115 of 11,875 patients underwent coronary angiography (CAG). The 115 patients had no significant stenosis on initial CAG and underwent repeat CAG for several reasons. Changes in lipid profile and other coronary risk factors were compared in 30 patients who developed ischemic cardiac events (Group E) and 85 patients who did not (Group NE). Ischemic cardiac events were defined as ischemic chest symptoms with ST-T changes or appearance of significant angiographic stenosis. At initial CAG, smoking was significantly more common in Group E (23.3% vs 4.7%, p0.01) and high-density lipoprotein cholesterol was significantly lower in Group E (42 +/- 11 vs 48 +/- 15 mg/dl, p0.05). At repeat CAG, smoking continued to be significantly more common in Group E (26.7% vs 10.6%, p0.05), and serum cholesterol (219 +/- 36 vs 193 +/- 34 mg/dl, p0.01) and low-density lipoprotein cholesterol (141 +/- 33 vs 115 +/- 29 mg/dl, p0.01) were also significantly higher in Group E. Multivariate analysis revealed only the increase of serum cholesterol at repeat CAG was a significant factor in the evolution of coronary artery disease (p = 0.026). Two patients from Group E died of cardiac causes within 1 year after repeat CAG but no patients in Group NE died (6.7% vs 0%, p0.05). Increased serum cholesterol level is related to the evolution of ischemic heart disease and cardiac death.

Echocardiographic findings, clinical features, and pathophysiology of mitral and aortic valve aneurysms were evaluated in four patients with pathologically proven aneurysms of the mitral and/or aortic valves associated with infective endocarditis. These four were selected from 20 patients hospitalized in our institute from April 1990 to May 1995 because of infective endocarditis. All four patients had received repeated, inadequate antibiotic treatments at other medical institutions prior to admission, and underwent surgical repair because of acute hemodynamic exacerbation associated with aneurysmal perforation. Six aneurysms (three mitral and three aortic valve aneurysms) were detected before surgery, including two by transthoracic echocardiography and four by transesophageal echocardiography. The echocardiographic findings typical of aortic valve aneurysm were: ringed echo at the level of the aortic annulus in the short-axis view; turbulent flow within the ringed echo; and dome formation of the aortic valve that persisted throughout the cardiac cycle. All mitral valve aneurysms were true aneurysms without active inflammatory changes or significant destructive lesions, and were associated with severe infective aortic regurgitation. Histologic examination of the aortic valve in these patients showed active inflammation and extensive destruction, suggesting that these valves were the primary focus of infection. One patient had an aortic valve aneurysm without apparent mitral involvement, indicating that another mechanism had mediated aneurysmal formation. We conclude that: diagnosis of mitral or aortic valve aneurysms in patients with infective endocarditis has important therapeutic implications, and therefore, transesophageal echocardiographic examination should be done in such patients: there are three key echocardiographically diagnostic findings of aortic valve aneurysm as mentioned above; and several unknown factors may contribute to aneurysmal formation of the mitral or aortic valve in patients with infective endocarditis.

The long-term (average: 10 years) outcome in 220 patients with double-vessel disease (DVD) treated medically was investigated. The patients underwent coronary angiography between September 1973 and February 1984, and significant (75% or more) stenosis was detected in each of two major coronary arteries. These patients showed relatively good 5-year and 10-year survival rates of 94.5% and 87.4%, respectively. Cardiac death occurred in 31 patients (14.1%) and nonfatal myocardial infarction (MI) developed in 16 patients (7.3%) during follow-up. When these were defined as cardiac events, the annual attrition rate was 3.1%. A comparison of the outcome with regard to the presence or absence of MI revealed worse results for the MI group, but no difference was observed between different sites of infarction. There was also no difference in outcome with regard to the presence or absence of lesions in the left anterior descending artery (LAD). In the MI group, patients with impaired left ventricular function (ejection fractionor = 40%) had inferior survival to those with good left ventricular function. Thus, DVD associated with good left ventricular function had a relatively good outcome when treated medically, while patients with impaired left ventricular function might benefit from revascularization.

The effect of medical treatment without reperfusion therapy on the long-term recovery of regional wall motion was evaluated retrospectively in 28 patients with transmural acute anterior myocardial infarction who had coronary angiography and left ventriculography at 1-6 months after the onset of the episode and were followed for a mean of 65 months. In all patients, initial coronary angiography revealed significant stenosis in only the left anterior descending artery (LAD). All patients were treated medically without reperfusion therapy (such as thrombolytic therapy, angioplasty, or bypass grafting). The regional wall motion in the LAD territory was measured by the centerline method using the right anterior oblique projection. Long-term improvement in anterior wall motion is unlikely in patients with patent LAD or underdeveloped collaterals to the LAD (38%). However, subsequent anterior wall motion frequently improved among patients with severely stenotic or occluded LAD (63%) and well-developed collaterals (73%). Therefore, the anterior wall motion of some LAD-related infarctions improves spontaneously, the extent of coronary collaterals is an important determinant of long-term improvement, and the improvement in wall motion is completed within the early period of acute anterior infarction in patients with patent LAD.

We have developed a method of measuring the isometric tension in glycerinated stalks of Vorticella convallaria. Using this method, we measured tension vs. pCa relations in glycerinated V. convallaria stalks. The maximum isometric tension was 4 x 10(-8) N on average. The Hill's parameter, n, which is the number of calcium ions bound simultaneously and cooperatively to a contractile element (a force generating element), is approximately 3.2 when the Ca2+ concentration is increased and 2.5 when it is decreased. In order to estimate the efficiency of the energy conversion of Ca2+ binding to mechanical work, we measured the Ca(2+)-induced Carnot cycle in the Vorticella stalk. The energy efficiency was tentatively estimated to be about 7%. With this method, we have also succeeded in measuring the isometric tension of isolated spasmoneme, the rubber-like contractile fibrous organelle in the stalk. The maximum tension of spasmoneme was approximately one tenth that of the glycerinated stalk. We speculate that the isolated spasmoneme was only partially functional due to damage sustained when it was pulled out of the stalk.

To evaluate the clinical usefulness of serum 1-methyladenosine, several modifications have been made in our previously established inhibition ELISA system. Horseradish peroxidase (HRP) labeled anti-mouse IgG and 3,3',5,5'-tetramethylbenzidine (TMBZ) were used as a secondary antibody and a substrate, respectively. The second blocking was done just before the addition of the secondary antibody. The standard curve of the modified ELISA system showed good linearity between 1 and 1,000 ng/ml, and the detection limit was 50 pg/well. Using the ultrafiltrated-serum samples, serum 1-methyladenosine levels in healthy individuals and cancer patients were determined. The mean level of 1-methyladenosine in 31 healthy individuals was 28.3 +/- 7.9 ng/ml, and cut off value was set at 44.1 ng/ml (Mean+ 2SD). In cancer patients, elevated levels of serum 1-methyladenosine above the cut off value were detected in 4 out of 25 cases tested, though 11 cases had elevated urinary 1-methyladenosine levels above the cut off value (3.23 nmol/mumol creatinine). Since 1-methyladenosine has no interaction with serum proteins and its molecular weight is quite low, it might be rapidly excreted into the urine.

To elucidate the mechanism of force generation by actomyosin motor, a measuring system was constructed, in which an in vitro motility assay was combined with an optical trapping technique. An actin filament of several micron long was attached to a gelsolin-coated polystyrene bead, and was allowed to interact with a small number (approximately 1/1 micron actin filament) of rabbit skeletal heavy meromyosin (an active subfragment of myosin) molecules bound to a nitrocellulose-coated coverglass. The bead position was determined at 33-ms intervals. We measured the force generation event at relatively low (100-400 nM) ATP concentration so that the occurrence of individual force generation events could be detected with our time resolution. The actin-bound bead held in the optical trap moved in a stepwise manner in the direction of the actin filament only in the presence of ATP. At the trap strength of 0.3 pN/nm, the maximum size of the step was 11 nm, and the maximum force associated with the movement was 3.3 pN.

This study was designed to test the hypothesis that high plasma lipoprotein (a) (Lp[a]) levels are associated with an increase incidence of restenosis after angioplasty. Elective transluminal coronary angioplasty was performed in 66 patients (58 men and 8 women) aged 57 +/- 9 years (mean +/- SD). Two days before and 5 days after angioplasty, all patients underwent low-density lipoprotein (LDL) apheresis with a dextran sulfate cellulose column as an Lp(a) absorbent; 39 patients also received 10 mg of pravastatin and 1,500 mg of niacin daily. Restenosis was defined as a recurrent luminal stenosis ofor = 50% in a previously dilated segment. Median Lp(a) levels were reduced from 23.3 mg/dl before apheresis to 10.9 mg/dl after apheresis (p0.0001). Angiography performed 2 to 9 months after angioplasty revealed restenosis in at least 1 site in 38% of the 137 control patients and in 32% of the 66 patients who underwent apheresis. Restenosis also occurred in 37% of the patients who underwent apheresis alone and in 28% of the patients who also received pravastatin and niacin in combination with LDL apheresis. The restenosis rate was 21% in the 42 patients whose Lp(a) levels were significantly reducedor = 50%, and in 50% of the 24 patients whose Lp(a) levels were significantly reduced50% (p0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Several years ago, we found a new chemical condition for the spontaneous oscillatory contraction of glycerinated skeletal muscle and named it "SPOC". The condition was such that MgATP coexists with its hydrolytic products, MgADP and inorganic phosphate (Pi). Micromolar concentrations of free Ca2+ were not necessarily required for this oscillation. Here, we summarize our recent work on the mechano-chemical properties of SPOC not only in glycerinated single fibers and myofibrils of skeletal muscle (fast type) but also in glycerinated small bundles of cardiac muscle; the isometric tension and its oscillation were examined at various concentrations of MgATP, MgADP and Pi while controlling the concentration of free Ca2+; we constructed a three-dimensional "state diagram" taken against the concentrations of MgADP, Pi and free Ca2+. The 3-D state diagram clearly showed the existence of three regions corresponding to three muscular states; the SPOC region was located in between the regions for contraction (without oscillation) and relaxation. Based on these results, we discuss the mechanism of SPOC, especially the minimum requirements for its occurrence. Finally, we suggest that slow shortening and quick lengthening repeatedly occur every half-sarcomere through the transition between the two states, where weak-force-generating complexes or strong-force-generating complexes are dominant; the transition may be induced by a coupling with the mechanical states of cross-bridges and/or thin filaments.

We have visualized, under an optical microscope, the orientations of actin monomers in individual actin filaments undergoing Brownian motion in solution, actively sliding past myosin molecules, or immobile on a surface. For the visualization, two strategies have been adopted. One is to exploit the fluorescence polarization of a fluorescent probe firmly attached to actin. Using the probe phalloidin-tetramethylrhodamine, the fluorescence was clearly polarized along the filament axis, showing alignment of the probe molecules along the filament axis. Within our temporal resolution of 33 ms and spatial resolution of better than 1 micron (average over approximately 10(2) actin monomers), the orientation of the probe (hence of actin monomers) did not change upon interaction of the filament with heavy meromyosin; myosin-induced reorientation was estimated to be a few degrees at most. This first method, while highly sensitive to small reorientations of monomers off or toward the filament axis, does not report on reorientations around the axis. To detect rotation around the filament axis, we adopted the second strategy in which we attached small plastic beads to the actin filaments. Axial turns would be immediately apparent from the movement of the beads. Preliminary observations indicate that actin filaments can slide over a heavy meromyosin-coated surface without axial rotations. Since rotations have been implicated in different experiments, we are currently investigating the source of the apparent discrepancy. The attached bead also serves as a handle through which we can apply force, via optical tweezers, on the filament. By letting the sliding actin filament pull the bead against the optical force, we were able to estimate the sliding force and its fluctuation.

Urinary levels of pseudouridine and 1-methyladenosine in patients with leukemia and lymphoma were measured by the inhibition ELISA using monoclonal antibodies to determine the correlation of nucleosides excretion with disease activity. Significantly elevated levels of these nucleosides were detected in patients with all types of disease tested. Seventy-seven percent (46/60) and 62% (37/62) of patients had elevated levels of pseudouridine and 1-methyladenosine above normal mean + 2S.D., respectively, and combination assay of these nucleosides gave higher positive rate (87%; 52/60) than either single assay. The changes of urinary pseudouridine and 1-methyladenosine reflected the disease status of patients in remission or in relapse and the effect of chemotherapy. These results suggest that urinary pseudouridine and 1-methyladenosine might be clinically useful as complementary markers to the monitoring of the disease status of patients with leukemia and lymphoma by hematological examination.