Airway responses to repeated exercises detected by krypton-81m in asthmatic children.

A repeated exercise program was used to test 7 asthmatic children for changes in ventilation. These changes were examined by continuously inhaled Krypton-81m and compared in subjects with positive and negative refractoriness, as defined by forced expiratory volume in 1 second (FEV1). Three of the seven patients showed significant refractoriness (% reduction in FEV1 > 50%). After the first exercise, they showed one or two ventilation defects which improved after the second exercise. The patient with incomplete refractoriness showed similar results. On the contrary, subjects without refractoriness showed several ventilation defects which fluctuated after the second or third exercise program. One defected area improved after the second exercise session, but deteriorated after the third; and another area deteriorated after the second exercise and improved after the third. It was concluded that approximately half of the patients were refractory in view of FEV1, but that they were all refractory in view of regional ventilation 81mKr images.     

Voltage-dependent inhibition of the delayed outward potassium current by OPC-8490, a novel positive inotropic agent,in isolated atrial myocytes of guinea-pig heart

Summary To elucidate the ionic mechanisms underlying prolongation of the action potential by OPC-8490, a novel positive inotropic agent, we examined effects of the drug on the membrane currents in isolated atrial myocytes of guinea-pig heart. The tight-seal whole cell clamp technique was used. In the current clamp condition, OPC-8490 prolonged the atrial action potential in a concentration-dependent fashion. In the voltage clamp condition, OPC-8490 affected neither the conventional L type Ca current nor the outward I _K1 current significantly. The drug blocked the delayed outward K current (I _K) in a concentration-dependent fashion. At a constant concentration of the drug, inhibition of _{I K} became more marked as the membrane potential became more negative. The tail current of I _K could be fitted by a sum of two exponentials (fast and slow components). OPC-8490 blocked the fast component more prominently than the slow one. Time constants of both components were not affected significantly by the drug. In conclusion, OPC-8490 prolongs the cardiac action potential mainly by blocking I _K in a voltage-dependent and time-independent fashion. Send offprint requests to Y. Kurachi at the above address     

Identification of a platelet-aggregating factor of murine colon adenocarcinoma 26: Mr 44,000 membrane protein as determined by monoclonal antibodies

The interaction between platelets and tumor cells plays an important role in the hematogenous spread of certain malignant cancers. We found that metastatic clones of murine colon adenocarcinoma 26 induced platelet aggregation in a membrane protein-dependent manner. Two monoclonal antibodies (mAbs) of IgG2a class were generated against a highly metastatic colon 26 clone, NL-17. These two mAbs, designated 8F11 and 20A11, showed a two-fold higher level of NL-17 binding than a low metastatic clone, NL-14, which possesses low platelet-aggregating ability. Both mAbs retarded platelet aggregation induced by NL-17. Western blot analysis showed that both mAbs recognized the same Mr 44,000 membrane protein as antigen under reducing conditions. Trypsin treatment of NL-17 diminished the ability of the cells to induce platelet-aggregation and resulted in a decrease in the reactivity of the cells to 8F11. These results suggest that the Mr 44,000 membrane protein recognized by the two mAbs is a platelet-aggregating factor of colon 26 cells.     

Mitral valve prolapse in patients with surgically-closed atrial septal defect

To evaluate the prevalence, causes and clinical significance of mitral valve prolapse (MVP) associated with surgically-closed atrial septal defect (ASD), 90 patients (M: 41, F: 49) were studied using two-dimensional and color-coded Doppler echocardiography. Among the 90 patients, preoperative echocardiograms were available in 27. MVP was found in 21 of the 27 patients (78%) preoperatively, but it was found in 59% (16/27) postoperatively. In total, MVP was detected in 50 of the 90 patients (56%) postoperatively. The postoperative MVP group had higher pulmonary-to-systemic flow ratios (3.6 +/- 1.9 vs 2.8 +/- 1.1, p less than 0.05) and higher mean pulmonary arterial pressures (21 +/- 11 vs 13 +/- 5 mmHg, p less than 0.01) at the time of surgery. Between the two groups with or without MVP postoperatively, there was no difference (p less than 0.05) in age at surgery, the postoperative duration and left ventricular (LV) deformity index both in pre- and postoperative states. A mitral regurgitant (MR) murmur was recorded in seven patients postoperatively. However, only two had clinically severe MR. It was concluded that MVP is frequently detected in patients with closure of ASD and it is related neither to degree of the LV deformity nor to age at operation; rather, it is related to the severity of the preoperative hemodynamic state. Clinically significant MR is rare in the postoperative period.     

Direct projections from the globus pallidus to the paraventricular nucleus of the thalamus in the rat

After injecting horseradish peroxidase into the thalamic regions around the paraventricular thalamic nucleus (Pv) in the rat, small neurons in the globus pallidus (GP) were labeled retrogradely with the ezyme. After injecting [³H]leucine into the GP, terminal labeling was autoradiographically observed in the Pv bilaterally with an ipsilateral dominance. These terminals in the Pv were shown by electron microscopic autoradiography to make asymmetrical synaptic contacts upon small dendrites of Pv neurons.     

Effect of medroxyprogesterone acetate on side effects of CAP therapy in gynecological malignant tumors

We concomitantly administered a large dose of medroxyprogesterone acetate (MPA) to gynecological malignant tumor patients undergoing CAP therapy (CAP). Hematological changes in the peripheral blood were compared between concomitant MPA patients and those not receiving MPA to examine the effect of MPA in reducing the marrow depression which is the major side effect of CAP. 1) Leukocyte count reached minimum at the second week of CAP in both groups. There was no significant difference in the count between the two groups. At the third week of CAP, the count improved to 84% of the pre-CAP level in patients receiving MPA and to 68% in those not receiving MPA, a significant difference (p less than 0.01). At the fourth week, leukocyte counts were 105% and 96% of pre-CAP levels, respectively. There was no difference between the two groups, but the leukocyte count returned to the pre-CAP level in the patients receiving MPA. 2) Platelet count showed changes similar to those in the leukocyte count. In patients receiving MPA, the count improved more rapidly within three weeks (118%, p less than 0.01), and was significantly higher at the fourth week (107%, p less than 0.05) than in patients not receiving MPA. 3) Reticulocyte count reached minimum in the first week, thereafter improving rapidly in both groups. No differences were noted between the two groups. 4) The periods needed for one course of CAP were 27.7 +/- 3.3 days in the patients receiving MPA and 29.5 +/- 3.7 days in the patients not receiving MPA, making for a significant difference between the two groups (p less than 0.05). These results show that MPA accelerates recovery from marrow depression caused by CAP. It is anticipated, therefore, that MPA will be helpful in the application of various chemotherapies which are expected to be frequently conducted in the future.     

Expression of P-glycoprotein mRNA in human gastric tumors

We have isolated a cDNA clone, pCA12-2, from a lambda gt11 cDNA library of an adriamycin-resistant subline of human myelogenous leukemia K562 (K562/ADM) by plaque hybridization with the 2.6 kb genomic probe of P-glycoprotein reported previously. The cDNA pCA12-2 was identified as the 3'-part of P-glycoprotein cDNA by dideoxy sequencing. By using the cDNA probe, expression of P-glycoprotein mRNA was examined in human gastric xenograft lines transplanted in nude mice and clinical samples of human gastric normal tissues and tumors. Five gastric tumor xenograft lines expressed low but significant levels of P-glycoprotein mRNA. The extent of expression was higher in some cases than that observed for R1-3, a weakly drug-resistant subline of K562. Normal gastric tissues from three patients expressed similar levels of P-glycoprotein mRNA and the extent of expression was slightly higher than that of R1-3. Two of three gastric tumor samples expressed higher levels of mRNA than normal gastric tissues. These results suggest that the intrinsic insensitivity of human gastric cancers to chemotherapy could be partly explained by the expression of P-glycoprotein.