Protective Effects of Dilazep and its Derivative K-7259 on the Haemolysis Induced by Amphiphiles in Rat Erythrocytes

The effects of dilazep and K-7259, a dilazep derivative, on the haemolysis (as evidenced by release of haemoglobin) induced by palmitoyl-l -carnitine (PAL-CAR) or palmitoyl 1-α-lysophosphatidylcholine (PAL-LPC) have been determined in rat erythrocytes. At concentrations above the critical micelle concentration both PAL-CAR and PAL-LPC induced haemolysis; the concentrations of PAL-CAR and PAL-LPC producing 50% haemolysis were approximately 13 and 14 μm , respectively. The 50% haemolysis induced by PAL-CAR or PAL-LPC was attenuated by dilazep (1, 10 or 100 μm ) but not at the highest concentration used (1 mm ). K-7259 attenuated the 50% haemolysis induced by PAL-CAR or PAL-LPC at concentrations ranging from 1 μm to 1 mm . Similarly, dilazep (1 to 100 μm ) and K-7259 (1 μm to 1 mm ) significantly or insignificantly attenuated the 25% and 75% haemolysis induced by PAL-CAR or PAL-LPC. Neither dilazep nor K-7259 affected micelle formation by PAL-CAR or PAL-LPC, nor, at concentrations of 1 and 10 μm , did they attenuate the haemolysis induced by osmotic imbalance (hypotonic haemolysis). These results suggest that both dilazep and K-7259 protect the erythrocyte membrane from the damage induced by PAL-CAR or PAL-LPC. The protective effects of dilazep and K-7259 are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance.     

Immunohistochemical studies on expression of human vascular smooth muscle myosin heavy chain isoforms in normal mammary glands, benign mammary disorders and mammary carcinomas

The expression of myosin in normal and diseased mammary glands of 199 Japanese women was evaluated immuno-histochemically by the avidin-biotin peroxldase complex method using antibodies to three human smooth muscle myosin heavy chain isoforms derived from the vascular smooth muscle: myosin SM1 is expressed consistently from fetal stage to adulthood, myosin SM2 appears only in well-differentiated smooth muscle after birth, and myosin SMemb is more abundant in embryonic aortas. SM1 was expressed in myoepithelial cells of normal mammary glands and fibrocystic diseases and in myoepithelial-like tumor cells In the basal layer of fibroadenomas and phyllodes tumors. SM2 was expressed only In the myoeplthelial cells of mammary glands in breastfeeding women. SMemb was expressed more Intensely In the cytoplasm of luminal epithelial cells in larger fibroadenomas ( P <0.01), or In the cytoplasm of carcinoma cells In lnvaslve ductal carcinomas with metastasized lymph nodes ( P <0.001) and In those of higher histological grade ( P <0.0001). Multivariate logistic analysis showed a significant correlation only between the expression of SMemb and histological grade ( P <0.0001), which is a prognostic factor of mammary carcinomas. These findings suggested the possible prognostic value of SMemb.     

Cytotoxicity Tests against Cultured Human Lung Cancer Cells With Autologous Lymphocytes Activated in vitro by Mitomycin C-Treated Tumor Monolayers in the Presence of T-Cell Growth Factor

Human peripheral blood or lymph node lymphocytes, obtained frompatients with a variety of lung cancer, were incubated in vitrowith mitomycin C-treated tumor monolayers in the presence ofT-cell growth factor. The cytotoxicity of these lymphocytesfor autologous tumor cells (autologous killer activity) wasassessed by a 4-hr ⁵¹Cr-release assay. Cytotoxic activity wasobserved in 14 out of a total of 20 cases. Lymphocytes frompatients with squamous cell carcinoma, large cell carcinomaand carcinoid exhibited positive activity levels of 11.1 ±1.8, 16.3 and 23.9% respectively. Nine out of 13 patients withadenocarcinoma exhibited positive activity with a mean valueof 8.8 ± 6.8%. No lymphocyte activity against small cellcarcinoma was observed. Natural killer (NK) activity did not always correlate with autologouskiller (AK) activity. Treatment of lymphocytes with monoclonalanti-human lymphocyte antibody revealed differences in effectorcell populations concerning these two activities; AK activitywas abrogated only by treatment with anti-human Lyt 3 antibodyand complement, whereas NK activity was abrogated by anti-humanLyt 1, 2 and 3 and partially by anti-human la antibody. Theseresults indicate that AK activity is mediated exclusively byT cells, but that NK activity is mediated by several subpopulationsof lymphocytes such as T cells, null cells and others.     

Epithelial cell proliferation during colonic chemical carcinogenesis in the rat

To define the significance of alterations in epithelial cell proliferation as a marker of high risk mucosa for colorectal cancer, we examined cell proliferative events in the colonic mucosa during chemical carcinogenesis using in vitro bromodeoxyuridine labelling and by analysing serial colonoscopic biopsy specimens from dimethylhydrazine (DMH)-treated rats. In both the rectum and flexure of the colon, an increased labelling index of colonic epithelial cells, an upward extension of the proliferating zone and an upward shift of the major area of DNA synthesis of epithelial cells were observed during DMH-induced colonic carcinogenesis in rats. These changes preceded the development of the colonic tumour and were observed in endoscopically normal rectal mucosa where the tumour was absent. We confirmed the altered cell proliferative events preceding the development of the tumour by examining serial colonoscopic biopsies. The results suggest that these alterations are features that identify premalignant colonic mucosa in DMH-treated rats.     

Acute urethritis caused by Neisseria meningitidis

A 48-year-old heterosexual Japanese man visited the outpatient clinic of Nagoya Urology Hospital, complaining of burning pain at voiding and pus discharge from the urethral orifice. These symptoms appeared the day following oral-genital contact (fellatio) with a commercial sex worker. On the basis of the presumptive clinical diagnosis of gonorrhea because of the microscopic detection of diplococci in the urethral discharge, he was treated with levofloxacin (300 mg per day) for 7 days. His symptoms responded quickly and urinalysis taken 7 days later was normal. Microbiological examinations isolated Neisseria meningitidis in the urethral discharge by culture with the use of enzymatic profiles. Further prevalence of sexually transmitted diseases (STD) through oral-genital contact would lead to an increase in meningococcal urethritis.     

Microwave Catheter Ablation Using a Clinical Prototype System with a Lateral Firing Antenna Design

Microwave has been considered a potentially more effective and more versatile form of energy than radiofrequency. Its feasibility has been tested using various prototype systems and catheter designs. This study assessed the safety and efficacy of a clinically-suitable prototype microwave power supply and catheter system with a lateral-firing antenna design for atrioventricular (AV) junction ahlation in canines and to correlate with tissue histopathology. The system consisted of a deflectable catheter with a 6-mm antenna and a thermocouple; and a 2.45-CHz frequency generator with power, time, and temperature controls. AV junction ablations were performed using 75 W energy for up to 60 seconds. Effective heating was confirmed hy a rise in catheter temperature to 69.3 ± 8.8°C. Complete AV nodal block was accomplished in all canines after an average of 4.1 ± 2.3 applications at 66.8 ± 7.7°C, and persisted after 28 days in all chronic animals. Lesions were consistent with thermal necrosis, were hemispherical to semi linear in shape and have distinct borders. Acute lesions were 3.4 ± 1.5 mm wide, 4.8 ±2.1 long, and 2.0 ± 0.9 deep. Chronic lesions showed typical healing and were smaller in size. Ablations did not cause any transvalvular, vascular or other cardiac structural damage, and no coagulum formation was noted on the antenna or catheter tip. Microwave AV junction ablation using this clinical prototype system specifically designed for it was safe and effective. Lesion's depth was limited to 5 mm with 60-second heating while its shape corresponded to the antenna's length. Microwave energy may provide greater versatility for producing discrete or linear ablation.     

Influenza virus and neurological diseases

Abstract  Influenza viruses rarely cause acute encephalopathy. Post-influenzal encephalitis, which occurs a few weeks after recovery from influenza is thought to be an autoimmune process associated with demyelination and vasculopathy. It has been suggested that Economo lethargic encephalitis followed by postencephalitic Parkinsonism was associated with the influenza A epidemic of 1918 (Spanish flu). The incidence of Reye's syndrome has markedly decreased due to the avoidance of salicylates in the treatment of influenza or varicella. One inactivated flu vaccine is thought to have caused Guillain Bane syndrome due to molecular mimicry between viral protein and myelin, which triggered autoimmune responses. The persistence of influenza virus genes in neural cells as one of the causes of chronic degenerative diseases of the central nervous system by inducing apoptosis of the host cells is yet to be proven.