The effects of nicorandil on electrophysiological changes in acute myocardial ischemia and reperfusion

This study was undertaken to clarify the effects of nicorandil on electrophysiological changes during acute ischemia and following reperfusion. We prepared an acute ischemic heart model by ligating the left anterior descending coronary artery in 27 dogs. After 10 minutes, reperfusion was performed. The changes in ventricular effective refractory period (ERP) and intramyocardial conduction time (ICT) were compared between the nicorandil group (n = 12) which received nicorandil intravenously before the coronary ligation and the control group (n = 15). In the control group, the ERP was shortened during ischemia, and rapidly shortened immediately after reperfusion, but was slightly prolonged 10 minutes after reperfusion. The ICT was prolonged during ischemia, but returned to the pre-ischemia value after reperfusion. In the nicorandil group, the changes in ERP and ICT were significantly inhibited compared to those in the control group. The incidence of ventricular fibrillation (VF) during reperfusion was 42% in the control group. However, there was no VF during reperfusion in the nicorandil group. Therefore, nicorandil may correct both the delayed conduction and the uneven ventricular effective refractory period detected during acute ischemia and following reperfusion, inhibiting the development of ventricular arrhythmia during reperfusion.     

A linear CMOS transconductance element of an adaptively biased source-coupled differential pair using a quadritail cell

A novel circuit design technique for realizing a linear CMOS transconductance element, consisting of an adaptively biased source-coupled differential pair using a quadritail cell, is proposed. In the circuitry, the quadritail cell, which provides an output current proportional to the square of a differential input voltage, cancels a nonlinear term of the source-coupled differential pair. The circuit have a superior linearity and a wide linear input voltage range compared with the conventional linear CMOS transconductance elements because the transconductance characteristic is theoretically linear over wide input voltage range when all the MOS field-effect transistors (MOSFETs) are operating in the saturation region and the MOSFETs' behaviors are according to the relation based on the square-law characteristic. The proposed adaptively biased source-coupled differential pair was verified by using transistor-arrays and discrete components on a breadboard.     

Transduction of the macrophage colony-stimulating factor gene into human multidrug resistant cancer cells: enhanced therapeutic efficacy of monoclonal anti-P-glycoprotein antibody in nude mice

To develop a therapeutic modality for overcoming multidrug-resistant (MDR) cancer with anti-MDR1 antibody, we examined the effect of macrophage colony-stimulating factor (M-CSF) gene transfection into MDR AD10 cells on therapy of MDR cancer with anti-MDR1 antibody (MRK17) in nude mice. MDR human ovarian cancer (AD10) cells were transduced with the human M-CSF gene inserted into an expression vector to establish gene-modified cells capable of producing low (ML-AD10), intermediate (MM-AD10) nd high (MH-AD10) amounts of M-CSF. Systemic administration of MRK17 resulted in significant dose-dependent inhibition of subcutaneous growth of ML-AD10 tumors. In contrast, systemic administration of recombinant M-CSF in combination with MRK17 did not augment the therapeutic efficacy of MRK17 alone, but rather promoted the growth of the parent AD10 cells. To test the efficacy of in vivo M-CSF gene therapy combined with antibody, we mixed the parent AD10 cells with MH-AD10 cells producing a large amount of M-CSF, and inoculated the mixed cells subcutaneously. Treatment with MRK17 inhibited growth of the mixed cells more than that of the parent cells alone. Thus, combined therapy with anti-MDR1 mAb and M-CSF gene modification of MDR cancer cells may provide a new immunotherapeutic modality for overcoming MDR in humans.     

Thermometry using 18 W carbon resistors in a temperature region around 10 mK

The resistance-temperature characteristics of $\text{1}\text{8}$ W carbon resistors of grade ERC-18SG, manufactured by Matsushita, with the nominal values of 48, 82, 100, 220, and 330 Ω have been measured in the region 4.2 K-25 mK and their application as thermometers in this region is confirmed. For the 82 Ω resistor, measurements were taken at temperatures below 10 mK. The temperature dependence of the resistance was found to be linear on the log-log plot over a wide range below 50 mK. The sensitivity remains finite even at 6 mK, but below 10 mK rapid measurements were prevented by a considerable increase in the thermal relaxation time. Measurement of the characteristics of several 100 Ω resistors from two different sets showed that resistors from the same set separate into two groups with different characteristics. This becomes appreciable at temperatures below 4.2 K, so it is difficult to predict the behaviour of Matsushita resistors below 4.2 K from the characteristics at higher temperatures.     

Hematopoietic cell transplantation in the twitcher mouse. The effects of pretransplant conditioning with graded doses of busulfan

The effects of congenic hematopoietic cell transplantation (HCT; transplantation of bone marrow and spleen cells) after graded doses of busulfan (BU), a myeloablative but nonimmunosuppressive alkylating agent, were evaluated in the twitcher mouse model of human galactosylceramidase deficiency, a demyelinating sphingolipid storage disease. C57BL/6 twitcher mice (immunophenotype Ly-5.1) were given 10 to 50 mg/kg of BU or total-body irradiation (9.0 Gy) at age nine days and HCT from congenic Ly-5.2 donors 24 hr later. The 30-day post-HCT survival, an indicator of tolerance of the preparative regimen, was at least 83% in twitcher mice given 45 mg/kg or less of BU, was 50% in recipients of 50 mg/kg BU and 75% in TBI-conditioned twitchers. The lifespan of twitcher mice given HCT after 10 or 20 mg/kg of BU was similar to that of untreated twitchers (median survival, 42 days; range, 30-47). In contrast, mice transplanted after 35 to 50 mg/kg of BU had significantly prolonged survival (median, 82 days; range, 56-208) and stabilization of hindlimb paralysis, similar to TBI-conditioned recipients. Post-HCT repopulation by donor Ly-5.2 cells was determined by flow cytometry. Thirty days after HCT, only 11-15% of lymphohematopoietic cells in blood, bone marrow, and spleens were of Ly-5.2 donor origin in twitcher mice transplanted after 10 mg/kg of BU but 60-80% were of Ly-5.2 donor origin in mice transplanted after higher doses of BU. These levels further increased to 70-90% by 90 days after HCT, comparable to that seen after TBI. Levels of galactosylceramidase in livers, spleens, and brains of twitchers transplanted after 35-50 mg/kg of BU or after TBI increased to 30-116% of normal control values by 90 days after HCT. Conditioning for HCT with as little as 35 mg/kg of BU provides minimal peritransplant mortality, rapid and sustained establishment of donor lymphohematopoiesis, replacement of lysosomal hydrolase, and prolonged survival in this murine model of human sphingolipidosis.     

New ion-implantation method for 4-µm period bubble device

It is well-known that bubble propagation margins for ion-implanted bubble devices depend strongly on ion-implantation conditions. A new ion-implantation method is reported that can significantly improve bubble propagation margins for minor loops with 4 × 4 μm bit cell size. The implantation was done through a Mo thin film layer so that the lattice strain and the anisotropy field change would be more uniform through the depth of the implanted layer. With this method, minor loops can be formed by hydrogen single implantation. Consequently simplification of the implantation process is achieved.