In vivo and in vitro studies of experimental ovarian adenocarcinoma in rats.

When 7,12-dimethylbenz[a]anthracene-impregnated sutures were directly applied to the ovarian parenchyma of 8-week-old Sprague-Dawley rats (the clipping method), adenocarcinomas developed in 29 (39%) of the 75 rats during the 50-week observation period. When 20-methylcholanthrene was used, adenocarcinomas developed only in 1 (3%) of the 31 rats. Thus, the clipping method using 7,12-dimethylbenz[a]anthracene is satisfactory as an animal model of ovarian adenocarcinoma which comprises 85 to 90% of human malignant ovarian tumors. On the other hand, attempts were made to isolate cloned cell lines from these experimental ovarian adenocarcinomas in vitro, and two cloned cell lines were obtained. They were epithelioid and produced undifferentiated adenocarcinomas by back-transplantation into isologous newborn rats.

Multi-institutional study of all-trans-retinoic acid as a differentiation therapy of refractory acute promyelocytic leukemia. Leukaemia Study Group of the Ministry of Health and Welfare.

We treated 70 acute promyelocytic leukemia (APL) patients with daily oral 45 mg/m2 all-trans-retinoic acid (ATRA) in two multi-institutional prospective studies. Of 64 evaluable patients, 21 were refractory to initial induction chemotherapy; 10 were refractory to salvage chemotherapy; 17, five, and four were in the first, second and, third relapse, respectively; and seven were previously untreated due to old age. In the first study with ATRA from China, 18 out of 22 (82%) evaluable patients achieved complete remission (CR). Initial peripheral leukemia cell counts were significantly less in the CR cases (p < 0.01); < 100/microliters in 17 out of 18 CR cases, and > or = 200/microliters in all failure cases. In the second study with ATRA from Hoffmann-La Roche, if initial leukemia cell counts were more than 200/microliters, chemotherapy was first given and then ATRA was started. Of 42 evaluable patients, 36 (86%) achieved CR. Morphological evidence of differentiation was noted in all CR cases. Patients achieving CR received standard consolidation and maintenance chemotherapies, and the 20-month predicted disease-free survival rate is 76% for cases achieving their first CR with ATRA. Toxicities attributable to ATRA were minimal and included cheilitis, xerosis, dermatitis, gastrointestinal disorders, bone pain, liver damage, and high serum triglyceridemia.

Differentiation of transiently ischemic from infarcted myocardium by thallium-201 exercises scintigram after active ergometer rehabilitation.

It has been frequently reported that while myocardial viability is neglected in conventional methods of diagnosis such as left ventriculography, ECG, and exercise thallium-201 myocardial scintigraphy (Ex-Tl), revascularization often results in improving left ventricular wall motility. In the present study, the authors contrived a method to accurately evaluate the viability of the myocardium by means of exercise rehabilitation, and tested the method in clinical cases. Among patients with myocardial infarction, we selected a patient with negative viability in the diseased area as determined by chronic ECG, left ventriculography (LVG), coronary angiography and Ex-Tl. This patient went through two weeks of active exercise rehabilitation gauged with an ergometer, and was then re-examined by Ex-Tl. After the evaluation, revascularization was performed for the patient who demonstrated viability of the infarcted myocardium in EX-Tl after rehabilitation, and significant improvement in contractility was shown in the chronic LVG. These findings indicate that our method of detecting potential viability of the infarcted myocardium is of clinical significance.

Allergic airway response and potassium channels: histamine release and airway inflammation.

The possible involvement of potassium (K) channels in allergic airway responses was examined in ovalbumin (OA)-sensitized guinea pigs. An ATP-sensitive K channel opener (BRL-38227) inhibited OA inhalation-induced bronchoconstriction and airway plasma leakage. BRL-38227 also had an inhibitory effect on exogenous histamine- and leukotriene-induced responses. In contrast, BRL-38227 did not affect OA-induced histamine release from minced lung tissues. Therefore, the ATP-sensitive K channel opener inhibits allergic bronchoconstriction and plasma leakage as a result of its effect on airway smooth muscle and postcapillary venules. Apamin, a small conductance Ca2+ -activated K channel (PK,Ca) blocker, significantly inhibited both OA-induced tracheal contraction and histamine release from lung tissues, suggesting that this compound reduces allergic airway responses via a mast cell stabilizing effect. We conclude that ATP-sensitive K channel opening and small conductance PK,Ca closure may be beneficial for preventing allergic airway responses.

[Analysis of the preceding R-R interval and the coupling interval on premature ventricular contractions].

Premature Ventricular Contractions (PVCs) are one of the common arrhythmias. Although the analysis of the preceding R-R interval and the coupling interval on the Holter electrocardiogram, the Lorenz plotting method, has been used to characterize mature of PVC, this analysis has typically been performed without regard to the morphological classification of the electrocardiogram waveforms. Therefore, we performed the Lorenz plotting after a PVC classification. We analyzed 45 cases with more than 1,000 PVCs per day. Twenty-six of the cases with PVCs had no organic heart disease (idiopathic PVC); nineteen of the cases with PVCs had organic heart disease (PVC with disease). Each R-R interval was analyzed after classification based on the morphology of each QRS wave of the PVC. The computer generated a two-dimensional plot of the relationship between the preceding R-R interval of PVC and the following coupling interval. The forms of PVCs were monoform in idiopathic PVC and were mostly multiform in PVC with disease. The patterns on Lorenz plotting in idiopathic PVC had a tendency to be uniform with small standard deviations. In contrast, multiform PVCs tended to be highly variable with large standard deviations. The value of SD was 32.1 +/- 12.0 msec in idiopathic PVC, and that of the slope "a" was 0.048 +/- 0.051 in PVC with disease. Using the SD values and the slope "a" values, we were able to classify idiopathic PVC vs. PVC with disease with a 95% sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

[Multiple liver abscesses due to Candida albicans in a patient with acute promyelocytic leukemia: percutaneous transhepatic intraportal administration of amphotericin B].

A 36-year-old male with acute promyelocytic leukemia in second relapse was admitted to receive reinduction therapy in June, 1985, and entered into third complete remission, but he developed spiky fever after chemotherapy. Ultrasonic tomography revealed multiple liver abscesses and culture of the aspirates demonstrated Candida albicans in the abscesses. He was treated with intravenous administration of amphotericin B (AMPH-B) but the effect on the liver abscesses was unsatisfactory and consolidation therapy was difficult to start. AMPH-B (30 mg/day) was administered by percutaneous transhepatic intraportal administration (PTIA). About two months later, multiple liver abscesses disappeared. No remarkable complications such as severe fever, chill and renal dysfunction were recognized during PTIA of AMPH-B. So PTIA of AMPH-B is considered to be useful and safe for the management of fungal liver abscesses.

[Development of acute myelocytic leukemia in the course of Sjögren's syndrome].

A 53-year-old female, who had been having xerostomia and xerophthalmia for two years, was admitted in November 1984, because of subfever and malaise. Laboratory examination revealed pancytopenia with appearance of blasts, mild hypergammaglobulinemia, and elevated titers of ANA, anti SS-A and anti SS-B. Bone marrow aspirate showed increased myeloblasts. Schirmer's test and Rose Bengal's test were both positive, and sialography showed apple tree like appearance. Pathological findings of biopsied lip mucosa showed remarkable infiltration of lymphocytes. The patient was diagnosed acute myelocytic leukemia and Sjögren's syndrome. In spite of recovery of peripheral blood after combination chemotherapy (BHAC-DMP), a disturbance of consciousness appeared and she died of its progression. It was suspected clinically that she was suffered from progressive multifocal leukoencephalopathy (PML). It is sometimes reported that patients with Sjögren's syndrome develop malignant lymphoma, but it is very rare that Sjögren syndrome develop AML.

[Combination chemotherapy (modified CHOP-Bleo) in non-Hodgkin's lymphoma].

Twenty-six adults with advanced non-Hodgkin's lymphoma (73% in clinical stage IV) were treated with a combination of cyclophosphamide, hydroxyldaunorubicin, vincristine, prednisolone and bleomycin (modified CHOP-Bleo), from May 1978 to July 1987. Complete remission (CR) was obtained in 12 of 26 patients (46%). The median survival time was 19.5 months (2-77 + months), Median duration of CR was 30.5 months (2-76 + months). The survival of patients with diffuse lymphoma large cell type (DL) was better than those with other diffuse lymphomas. The 50% of patients with DL are projected to be free of disease. The survival of patients with clinical stage III was significantly better than those with clinical stage IV. Major complications during chemotherapy with modified CHOP-Bleo were myelosuppression, constipation and peripheral neuropathy. These toxicities were generally mild and well tolerated.

[A case of aortitis syndrome].

A 57 years old woman was admitted for the investigation of anginal chest pain. Her coronary angiography didn't show any typical finding seen in the aortitis syndrome, but coronary sclerosis and stenosis seen in the usual atherosclerotic patients. The cerebral angiography was performed, too. The right vertebral artery, which was tortuous and dilated, was seen, but the other three cerebral vessels were not seen. These rare findings were reported in this report. We added the discussion about the relation between the aortitis syndrome and angina pectoris.

[A case of giant cell myocarditis associated with a progressive disturbance in the conduction system].

A 73 year old male patient with a history of pulmonary tuberculosis was admitted to our department because of dyspnea and abdominal pain. The chest X-ray film on admission showed bilateral lung congestion. The ECG showed atrial fibrillation, left axis deviation and incomplete right bundle branch block. Five days after admission, the ECG changed into sinus rhythm and complete right bundle branch block. Eight days after admission, the patient complained of chest pain and the ECG showed ST elevation in II, III, aVF, reciprocal ST depression in V, and complete A-V block with junctional rhythm. Emergency coronary angiography revealed no significant stenosis. Echocardiography showed reduced contraction of the inferior wall and diffuse granular echoes in the myocardium. Light microscopic study revealed fibrosis, infiltration of eosinophils and histiocytes, degenerated myocardium and multinucleated giant cells. Some of the giant cells were morphologically similar to myocardium, so the myocardium might be a place of immunological reaction.

[The study for the standard of the remission of the patients with trophoblastic disease (author's transl)].

The recurrence of the patients who had obtained remissions once was studied and the standard of remission was reassessed. The comparison of the titers of hCG ranged the LH levels was studied by means of some methods of measurement. 1) During 7 years, from 1973-1979, 141 patients with trophoblastic disease in Chiba University Hospital were treated. The remission rate was 92.2% (130/141), the recurrence rate was 6.2% (8/130). In the high risk group, the recurrence rate was 23.1% (6/26), in the low risk, it was 1.9% (2/104). Four of 8 with recurrence were died, 4 (2 high risk and 2 low risk) obtained remissions again. 2) The mean HCG titers of patients with recurrence were 29.5 +/- 23.5 IU/L (HAR), 13.7 +/- 6.4 mIU/ml (HCG-RIA), 1.5 +/- 0.7 ng/ml (HCG-beta RIA) and that of patients with remission were 13.8 +/- 13.0 IU/L, 11.3 +/- 4.1 mIU/ml, 1.0 +/- 0.6 ng/ml, respectively. 3) The 2 patients whose HCG titers indicated all negative followed the recurrences. The HCG beta titers of the patients who were extirpated their bilateral ovaries indicated rather high in spite of getting their remissions. 4) The essential standard of remission was the equanimity of the HCG titers around the negative levels without disturbance by LH or other substances for a while. But it is not enough for a remission.

The antigenic determinants, Rg/Ch/WH, expressed by Japanese C4 allotypes.

The expression of antigenic determinants, Rg/Ch/WH, on Japanese C4 allotypes has been studied. Although the Japanese C4 allotype frequencies are known to differ from Europeans, the antigenic expression of their C4 allotypes correlates with associations described previously. All 89 random donors and 17 selected donors were Rg:1,2 so neither Rg:1,-2 nor Rg:1,-2 was found. The frequency of Ch:1,-2,3 was elevated while that of Ch:1,2,3 was reduced, which was seen as a direct result of the higher frequency of B2 and B5 allotypes. None of the Japanese were Ch:1,2,-3, but this can be accounted for by the absence of the A*6,B*1 haplotype. The WH determinant, which has been associated completely with Rg:1,-2 in Caucasians, was found at a higher frequency, 32%, in association with an A*3,2,B*QO haplotype expressing Rg:1,2, which has not been described previously. Detailed investigation showed that the A3 allotype was Rg:1,2 whereas the A2 allotype only expressed Rg1 (Rg:1,-2 WH+).

Platelet calmodulin correlates with platelet turnover.

We measured the calmodulin content in platelets in 13 normal persons and in 62 patients with hematological diseases. The level of platelet calmodulin was higher in patients with idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus, myeloproliferative disorders, acute leukemia in a recovery phase, aplastic anemia, thrombosis and hypersplenism as compared to the controls. Among the patients with ITP, calmodulin was lower in responders than in nonresponders and those at the initial diagnosis. We also measured the volume, life-span and aggregation of the platelets and demonstrated a significant relationship between the calmodulin level and the platelet volume, and a negative relationship between the calmodulin level and platelet life-span, there was no correlation between the calmodulin level and platelet aggregation. We thus conclude that platelet calmodulin is inversely correlated with platelet turnover.