A possible involvement of oxygen free radicals in the development of myocardial acidosis during coronary occlusion in dogs

Summary The present study was designed to examine whether free radical scavengers attenuate myocardial acidosis induced by partial occlusion of the coronary artery in dogs. The myocardial pH was determined by a micro glass pH electrode inserted in the endocardial layers of the left ventricular wall perfused by the left anterior descending coronary artery. The left anterior'descending coronary artery was occluded for 90 min incompletely so that the flow would be 1/2–1/3 the original flow. The myocardial pH before partial occlusion was 7.54–7.55. Partial occlusion decreased the flow in the left anterior descending coronary artery by 49.3–64.9% and the myocardial pH by 0.71–0.76, and increased the ST segment (surface electrocardiogram) by 6.3–9.3 mV. Saline (0.5 ml/kg), recombinant human superoxide dismutase (70,000 or 210,000 U/kg), or catalase (55,000 or 165,000 U/kg) was injected intravenously 30 min after partial occlusion. The injection of recombinant human superoxide dismutase or catalase alone did not restore the myocardial pH that had been decreased by coronary occlusion. The combined injection of recombinant human superoxide dismutase (70,000 U/kg) + catalase (55,000 U/kg), however, restored the myocardial pH without restoration of ST segment. In conclusion, recombinant human superoxide dismutase + catalase attenuated myocardial acidosis during ischaemia, suggesting a possible involvement of oxygen free radicals in the development of myocardial acidosis (especially in the endocardial layers) during ischaemia. Send offprint requests to Y. Abiko at the above adress     

Effect of beraprost sodium on peripheral circulation insufficiency in rats and rabbits

Beraprost sodium (sodium (+/-)-(1R*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is a chemically and biologically stable epoprostenol analogue which possesses both potent antiplatelet and peripheral vasodilating actions. Its effect on obstruction of the peripheral artery was studied in three different models: 1. acute thrombosis induced by electrical-stimulation of the femoral artery in rabbits, 2. occlusion induced by intra-arterial injection of sodium laurate in rats and 3. tail gangrene induced by subcutaneous injections of both ergotamine and epinephrine in rats. Oral administration of beraprost sodium resulted in suppression of thrombus formation in the acute thrombosis model, marked improvement of macroscopic and histological observations in the laurate-occlusion model and inhibition of tail gangrene extension. In contrast, ticlopidine improved thrombus formation in the acute thrombosis model and slightly improved histological observation in the laurate-occlusion model, but not in the tail gangrene model. Cilostazol suppressed lesions in the acute thrombosis model, but not in the tail gangrene model. These findings suggest that beraprost sodium may be very useful clinically for the therapy of peripheral circulation insufficiency diseases such as Buerger's disease and Raynaud's disease.     

The effect of a new immunosuppressive agent, FK-506, on xenogeneic neural transplantation in rodents--comparison with cyclosporin A]

The present study was performed to compare the immunosuppressive effect of FK-506 (FK) with cyclosporin A (CyA) in xenogeneic neural transplantation in rodents. The solid grafts of embryonic ventral mesencephalic tissue from 14-day rat embryos were transplanted into the right lateral ventricle of 20 mature male mice using a stereotactic approach, and the mice were sacrificed 14 days after transplantation. The removed brains, which were sectioned coronally, were stained with antibodies against glial fibrillary acidic protein (GFAP), Lyt-2 or tyrosine hydroxylase (TH) in addition to hematoxylin-eosin and Nissl stainings. The subcutaneous (s.c.) administration of FK at a dose of 10.0 mg/kg daily for 14 days enabled the neural xenografts to survive and grow (n = 5), although all of the neural xenografts treated with CyA at a dose of 10.0 mg/kg s.c. (n = 5) or FK at a dose of 1.0 mg/kg s.c. (n = 5) daily for 14 days and ones treated without such an immunosuppressive agent (n = 5) were rejected by immunological reactions. We conclude that FK is a more powerful immunosuppressive agent than CyA in xenogeneic neural transplantation as well as in cardiac and renal allograftings.     

Nucleolar organizer region score and Ki-67 labelling index in high-grade gliomas and metastatic brain tumours

Summary Sixteen cases of malignant brain tumours comprising 6 anaplastic astrocytomas, 3 glioblastoma multiforme, 1 medulloblastoma and 6 metastatic brain tumours were investigated independently by a silver colloid method for nucleolar organizer regions (NORs) and an immunohistochemistry using a monoclonal antibody against a nuclear antigen, Ki-67, in proliferating cells. The correlation between the mean number of NORs and the percentage of Ki-67 labelled cells (Ki-67 labelling index) was examined. In addition, four normal brain tissue samples without neoplastic cells were stained for NOR.The mean number of NORs in these malignant brain tumours was significantly greater than that in normal astrocytes (p<0.001). Moreover, both the mean number of NORs and the Ki-67 labelling index in metastatic brain tumours were significantly greater than those in high-grade gliomas (p<0.001). The Ki-67 labelling index and the mean number of NORs in malignant brain tumours including metastatic brain tumours were found to be linearly related (r=0.86).These results suggest that the proliferative potential of malignant brain tumours could be evaluated by NOR score as well as Ki-67 labelling index and that such indices provide clear discrimination between high-grade gliomas and metastatic brain tumours.     

Regulatory mechanisms for the expression of a functional beta chain of interleukin 2 receptor on T4 chronic lymphocytic leukemia cells.

Monoclonal antibodies, each recognizing interleukin 2 receptor (IL-2R) alpha, or beta, were used to see the regulatory mechanisms of the expressions on leukemic cells from a patient with T4 chronic lymphocytic leukemia (T4-CLL). Cells from this patient expressed only IL-2R beta, and the expression was enhanced by medium cultivation. IL-1 enhanced the expression of not only IL-2R beta but also IL-2R alpha on the cells. Binding studies using 125I-IL-2 showed the presence of an intermediate receptor (734 sites/cell, Kd = 1.2 nM) and a few high-affinity receptor (172 sites/cell, Kd = 132 pM) on cells cultured with IL-1. IL-2 and IL-1 synergistically promoted the proliferation of the cells, suggesting that the induced IL-2R was functional. In addition, anti-IL-1 antibodies inhibited IL-2R beta expression by cultured cells, suggesting that it was dependent on IL-1 produced by the leukemic cells. These findings suggested that IL-1 might enhance the expression of IL-2R beta in a subset of human T cells, and implied a role of IL-1 in the proliferation of the leukemic T cells.     

Factors associated with high density lipoprotein cholesterol in Japanese and American telephone executives.

The association of plasma high density lipoprotein cholesterol (HDL cholesterol) with several factors was examined in a cross-sectional study of Japanese and American telephone executives. Mean HDL cholesterol levels were similar in both groups of men and were negatively associated with body mass index, smoking, and serum uric acid and positively associated with alcohol and exercise. These associations did not differ between the Japanese and the American men. The mean HDL cholesterol level was 4.2 mg/dl lower in the Japanese than in the American men after adjusting for age, body mass index, alcohol, smoking, exercise, and serum uric acid. The difference in HDL cholesterol between Japanese and American men in this study is inconsistent with the much lower coronary heart disease mortality in Japan and with previous comparison studies of these two populations. Most previous studies have not adjusted for important confounders, but the selective nature of our study groups may have also contributed to this inconsistency. These racial differences in HDL cholesterol may also be due to either genetic or unmeasured environmental and cultural differences. Given the similarity in HDL cholesterol levels between these two groups, our results suggest that HDL cholesterol does not play an important role in the lower coronary heart disease mortality in Japanese men.     

Surgical indication to deep-seated arteriovenous malformation

The natural history of cerebral arteriovenous malformation (AVN) is still a subject of dispute. In the case of deep seated AVM ruptures, the problem is more serious because the hemorrhages often give rise to severe disability or death, depending on their location. Total extirpation of the nidus is fundamentally the best choice for treatment of AVM. It is never acceptable, however, to allow a persistent post operative deficit. Forty-seven cases of deep AVM were encountered in the Tokyo Jikei University Hospital. Total extirpation of the nidus was successful in 32 cases, while no surgery was undertaken in 15. Up to the present time we have taken three risk factors into condition in judging the indications for deep seated AVM surgery: the size of the nidus, the position of the nidus, and the pattern of demarcation around nidus, as shown on CT scan. When the nidus is bordered by a hemorrhage, cyst, or ventricular wall, dissection of the nidus is facilitated and injury to adjacent brain tissue is minimized, and this is why we included profound demarcation around the nidus as the third factor. We then determined grade of risk with respect to each factor, and counted a risk score in each case. The long-term result was judged by the response to questionnaires. Of the 15 patients who did not undergo surgery, four died on account of rebleeding. The longer the patient having deep AVM survived, the more likely the occurrence of fatal rebleeding. Of the 32 patients operated on, two died immediately after surgery, while 23 survived in an improved state or without any aggravated neurological deficit.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary embolism and cerebral venous thrombosis after thoracoscopic surgery for benign pulmonary disease

A-76-year-old woman consulted for open biopsy for a pulmonary mass. Thoracoscopic wedge resection was performed. The lesion was histologically diagnosed as nonspecific inflammation. On the first postoperative day (POD1), the patient lost consciousness transiently. Eleven hours after the first stroke, the patient experienced a second stroke together with hypoxia. Pulmonary perfusion scan on POD2 showed multiple perfusion defects, and the patient was diagnosed with pulmonary embolism (PE). Thrombolitic therapy was started. Neurological symptoms didn’t improve, and cerebral angiography on POD3 showed delayed perfusion in superficial veins. The patient was diagnosed with cerebral venous thrombosis (CVT). Thrombolytic and anticoagulant therapy had been continued, and the patient was found to have hemorrhagic cerebral infarction on POD11. After persistent therapy, the patient was discharged on POD120. Although both PE and CVT are rare complications after thoracic surgery, we must consider these complications in patients undergoing thoracic operations including thoracoscopic surgery.