Acta Medica Okayama 48巻 2号

Effects of acute (15h) and chronic (15h x 7 days) immobilization (IM) stress on plasma levels of nicorandil [N-(2-hydroxyethyl) nicotinamide nitrate (ester)] administered orally were examined in rats. The maximum plasma level was reached 30 min after administration. Acute IM stress significantly reduced plasma nicorandil levels both in the absorption and elimination phases (15 min and 2-6h after administration, respectively). Chronic IM stress further intensified the reduction of nicorandil levels in the absorption phase, but attenuated the influence of acute stress in the elimination phase. No significant difference was observed one day after removal of chronic IM stress. These results suggest that chronic IM stress markedly inhibits the absorption of nicorandil, but the distribution, metabolism and excretion were influenced more by acute IM stress.

Previously, we reported that interleukin-2 (IL-2)-stimulated helper T cells produced an unknown soluble factor which induced dendritic cell-like differentiation in primary cultures of monocytic leukemia cells and we referred to this factor as dendritic cell differentiation factor (DCDF). In this study, we attempted to purify and characterize DCDF and investigated its biological effect on normal human monocytes. Gel filtration chromatography indicated that the molecular weight of DCDF is approximately 30-35 kDa. Chromatofocusing indicated that the isoelectric point of DCDF is approximately 5.0. DCDF, partially purified by subsequent gel filtration, chromatofocusing, and hydrophobic chromatography, significantly enhanced the HLA-DR expression of normal human monocytes and a human monocytic leukemia cell line, THP-1. This biological activity was not neutralized by any known antibodies to human cytokines. DCDF significantly amplified the T-cell stimulatory activity of monocytes in the allogeneic mixed leukocyte reaction (MLR). Moreover, DCDF significantly enhanced IL-1 beta and IL-6 production by monocytes in a dose-dependent manner. These results suggest that DCDF is a novel human cytokine which stimulates the accessory cell function of monocytes.

Nipradilol is a newly synthesized beta-blocker which has a propranolol-like structure and contains a nitrate moiety. To examine the effect of nipradilol on venous blood flow, a single oral dose of nipradilol (6 mg) and propranolol (20 mg) was administered in the same 15 normal volunteers on separate days. Peak flow velocities, flow velocity integrals, and the diameter of the right brachiocephalic vein were measured before and 2 h after drug administration using Doppler echocardiography. These two beta-blockers significantly decreased systolic blood pressure to the same extent as they did heart rate. Nipradilol dilated the venous diameter by 8% and decreased peak flow velocity by 8% during systole and 9% during diastole. The flow velocity integral in one cardiac cycle also decreased significantly by 14%. Propranolol, however, failed to modify these parameters. These results suggest that nipradilol decreased venous return through its nitroglycerin-like direct vasodilating action.

Anodal direct currents at intensities ranging from 0.3 to 30.0 microA were unilaterally applied for 30 min once a day to the premotor area of the rabbit cerebral cortex. The anodal polarization was repeated 10 times at intervals of 2-3 days, and the effect on the motor activity of the forelimbs during and after each polarization trial was compared with that before polarization. Peripheral motor activity was classified as either gentle flexion of forelimbs or struggle with violent movement of forelimbs. A current of 0.3 microA caused no change in motor behavior. Flexion of the forelimb contralateral to the polarized cortex was clearly increased when a polarizing current of 1.0 or 3.0 microA was applied, and peak flexion was observed between the third and seventh polarization trials. A current of 10 or 30 microA had no effect on forelimb flexion. Conversely, forelimb struggle on both sides was decreased when 10.0 or 30.0 microA, but not 1.0 or 3.0 microA, was applied. These results show that anodal polarization of the cerebral cortex exerts dual effects on peripheral motor activity, probably through changes in cortical excitability associated with the current intensity.

Cytotoxic lymphocytes, including natural killer cells, lymphokine-activated killer cells, and cytotoxic T lymphocytes, adhere to and lyse cancer cells by recognizing cell surface antigens. Among the cell surface antigens, intercellular adhesion molecule-1 (ICAM-1) and HLA class I antigen are important for the cytotoxic activity of lymphocytes. The ICAM-1 and HLA class I antigen were examined in gastric cancer cell lines MKN-28 and MKN-45 by flow cytometry to determine whether their expression on the cell surface is enhanced by interferon gamma (IFN-gamma). The cell expression rate [stained cells/10(4) cells x 100(%)] was only 10% in ICAM-1 and about 20% in HLA class I antigen without IFN-gamma, but reached 70% in ICAM-1 and up to 60% in HLA class I antigen after incubation with IFN-gamma for 24-96 h. This enhanced expression of cell surface ICAM-1 and HLA class I antigen by IFN-gamma might increase sensitivity for cytotoxic lymphocytes.

Pulmonary metastatic tumors in two patients with locally well controlled uterine cancer were treated with bronchial arterial infusion chemotherapy. The first patient underwent a radical hysterectomy and pelvic lymphadenectomy for stage IIb cervical cancer. Fifteen months after the operation, pulmonary metastasis was identified. Clinical evidence of tumor was negative after bronchial arterial infusion chemotherapy, systemic chemotherapy and radiotherapy. The patient continues to be healthy without recurrent signs six years after bronchial arterial infusion chemotherapy. The second patient underwent a radical hysterectomy and pelvic lymphadenectomy for stage II endometrial cancer. Fifteen months after the operation, pulmonary metastasis was identified. After bronchial arterial infusion chemotherapy and systemic chemotherapy, regression of the tumors was observed. This patient has also survived for two years since the lung metastases. These results indicate that bronchial arterial infusion chemotherapy is a potent treatment for pulmonary metastases of uterine cancer.

The functional roles of the three-dimensional fibrillar ultrastructure of the proximal interphalangeal joint volar plates of human fingers were studied by light microscopy and scanning electron microscopy. The results revealed that the volar plate consists of three layers of fibers. The first layer forms an intracavity wall with two parts, the proximal "membranous portion", and the distal "meniscoid protrusion" that is separated from the middle phalangeal base by a "recess". The second layer contains the "check ligament", which lies parallel to the fibers of the tendon, anchors tightly into the middle phalangeal base, and protects the joint from hyperextension. The third layer connects to the fibers from the accessory ligament and ligamentous tendon sheath of the A3 pulley, perpendicularly crosses the fibers of the tendon, becomes the periosteum of the middle phalangeal base, and functions as a hanging support for the volar plate and as a gliding floor for the flexor tendon.