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A result of mass-screening for uterine cervical cancer conducted by Hyogo Cancer Hospital performed using mobilunit from 1965 to 1978 was analyzed and presented in this paper. The total number of women taking our initial screening examination was 188, 183.5% women screened or 9,447 were transferred for the further accurate examination. The rate of participants for this 2nd examination was 93.8% on the average. In this initial screening examination, a result of cytological examination on Papanicolaou's classification was as follows; 94.87% for class I and II, 4.81% for class III, and 0.21% for class IV and V. In the 2nd examination, the rate of the negative, suspected positive were 70.6%, 22.5% and 6.9% respectively. 759 cervical cancers were detected in our screening. The detecting rate of cervical cancer was 0.4% among initially screened women and 8.6% among women who appeared for the accurate examination. As the detecting rate among women for the 2nd examination became higher year by year (20% increase during recent 3 years), the accuracy of our screening methodology appeared to be improving. The incidence rate of cervical cancer in our screening was classified as stage 0; 49.0%, Ia; 36.4%, Ib; 9.1%, II; 3.9% an III; 1.6%. The most of detected cancer was occupied by cancer in situ and early invasive cancer. Annual review showed there is a gradual and steady increase in incidence rate to stage 0 in our screening.

In order to evaluate the etiology of so-called idiopathic ventricular tachycardia, endomyocardial biopsies were performed in four patients with electrocardiographically documented recurrent and sustained ventricular tachycardia. During the episodes of ventricular tachycardia, standard ECG showed a QRS pattern of right bundle branch block with left axis deviation in two patients and left bundle branch block in two patients. The episodes were associated with palpitation, dyspnea and hypotension in all cases. No organic heart disease was detected by physical examination, chest X-ray films, echocardiograms, left ventriculograms or coronary cineangiograms. His bundle electrograms showed blocks at various sites in the atrioventricular conduction system. The biopsy specimens revealed nonspecific myocardial degeneration in the right and left ventricles. These findings suggest mild but wide-spread myocardial damage in both the working myocardium and the conduction system. The clinical course of these patients appeared benign according to follow-up data of one to nine years' duration. None developed overt clinical signs of dilated, hypertrophic or restrictive cardiomyopathy.

This light- and electron-microscopic study using monoclonal antibodies provides an immunohistochemical demonstration of lymphocytes in situ in the myocardium in murine coxsackie B3 virus myocarditis. On the 7th and 9th days after virus inoculation, we observed many necrotic cardiocyte foci infiltrated with numerous inflammatory cells including macrophages and T lymphocytes. There were only a few Lyt 1-bearing lymphocytes in this phase of inoculation. On the 14th day there were many Lyt 1-bearing cells among the T cells in the foci. By immuno-electron microscopy, some Lyt 1-bearing T lymphocytes were seen in close contact with macrophages and/or other lymphocytes. These Lyt 1-bearing lymphocytes appeared to represent helper T cells, although Lyt 2.3+ lymphocytes were not examined. It is well known that activation of helper T cells leads to stimulation of B cells and cytotoxic T cells. It is assumed, therefore, that Lyt 1-bearing T lymphocytes that infiltrated into the myocardial foci play an important role in immune responsiveness at this stage of viral myocarditis.

In 113 patients with idiopathic cardiomyopathy paired sera obtained 2--4 weeks apart were examined for neutralizing antibody to coxsackie B 1--6, and echo 4, 6, 7, 9 and 11 viruses. Only eight cases (6.9 per cent) showed a significant change in titer, indicating a virus infection during or shortly before the study. Complement-fixing antibody titers were measured in 126 patients and neutralizing antibodies in 116 patients with idiopathic cardiomyopathy. More patients had complement-fixing antibody titers greater than or equal to 1 : 4 to coxsackie B and herpes simplex virus than did controls (p less than 0.05). Neutralizing antibody titers to coxsackie B 1 and B 3 virus were also higher in patients (p less than 0.01 for titers greater than or equal to 1 : 4 and p less than 0.05 for titers greater than or equal to 1 : 16). Complement-fixing antibody titers greater than or equal to 1 : 4 to herpes simplex virus were more frequent (p less than 0.05) in hypertrophic cardiomyopathy and those to coxsackie B, herpes simplex and influenza A virus were more frequent in congestive cardiomyopathy. Neutralizing antibody titers were more common to coxsackie B 3 (p less than 0.05 for titers of greater than or equal to 1:4) in hypertrophic cardiomyopathy, while in congestive cardiomyopathy they were more common to B 1 (p less than 0.01 for titers greater than or equal to 1 : 4 and p less than 0.05 for titers greater than or equal to 1 : 16), to coxsackie B 3 virus (p less than 0.001 for titers greater than or equal to 1 : 4 and p less than 0.04 for titers greater than or equal to 1 : 16) and to coxsackie B 5 (p less than 0.05 for titers greater than or equal to 1 : 4 or more) and to echo 6 virus (p less than 0.05 for titers greater than or equal to 1 : 4 and greater than or equal to 1 : 128). Immunofluorescent study of 61 cases showed no virus antigens in the biopsied myocardium even in patients who had significant changes in neutralizing antibody titers in paired sera. These results suggest a relationship between virus infection and idiopathic cardiomyopathy not only of the congestive type but also of the hypertrophic type. However, they do not provide definite proof of the virus infection theory of the disease.

This light- and electron-microscopic immunohistochemical study using monoclonal antibodies analyzes of the in situ lymphocyte subsets in endomyocardial biopsies from 11 patients with dilated cardiomyopathy (DCM) and three patients with idiopathic (viral) myocarditis (MYO). In the DCM patients both Leu 2a+ cytotoxic/suppressor T cells (Tc/s) and Leu 3+ helper/inducer T cells (Th/i) were identifiable in the myocardial lesions, and mean Th/i/Tc/s (T4/T8) ratio was 0.7 +/- 0.6 (mean +/- SD). In 9 of the 11 DCM patients, Tc/s were more numerous than Th/i cells, so the T4/T8 ratio was less than 1.0. On the other hand, the T4/T8 ratios varied widely in the three MYO patients; one of them had marked mononuclear cell infiltrates with many Th/i in the inflammatory foci and a T4/T8 ratio of 2.6. Immunoelectron microscopy revealed some Th/i in close contact with macrophages. These T cells in the myocardium of DCM and MYO patients appeared to be in vivo effector cells playing an important role in cell-mediated immune responses.

To correlate left ventricular function and histologic features in patients with dilated cardiomyopathy, precise indexes of hemodynamics and semiquantitative histologic data were combined for multivariate analysis. Right endomyocardial biopsy was performed at the time of cardiac catheterization. Five hemodynamic indexes were used for functional assessment: ejection fraction, ratio of end-systolic stress to volume index, end-diastolic stress, time constant (T) of left ventricular pressure fall, and end-systolic stress. Six histologic findings (disarray of myofibers, hypertrophy of myofibers, scarcity of myofibrils, nuclear changes of myofibers, vacuolization of myofibers and proliferation of collagen fibers) were graded from (-) to (4+). Each finding was assigned to category (-) or (+) according to the absence or presence of significant abnormality. Ordinary statistical analysis revealed that, although ejection fraction was lower in category (+) for proliferation of collagen fibers, ratio of end-systolic to volume index was reduced for category (+) of hypertrophy of myofibers. A significant correlation was present between hypertrophy of myofibers and proliferation of collagen fibers by Spearman rank correlation. When principal component analysis was applied to the hemodynamic data, two principal components could be extracted. Fisher's discriminant analysis could clearly differentiate two categories (-) and (+) in the semiquantitative histologic finding of proliferation of collagen fibers. The analysis indicated that contractility was reduced with elevated afterload in that category (+). Thus, proliferation of collagen fibers may play a pivotal role in deteriorating contractility in patients with dilated cardiomyopathy.

The hemodynamic changes of the left ventricle (LV) of golden hamsters surviving for 14 months after acute coxsackie B3 virus myocarditis were assessed with the use of a high fidelity micromanometer pressure system. Of 25 infected hamsters, 10 survived to the 14th month, and 4 of these had cardiomegaly. Body weight (BW) was 150.0 +/- 20.7 g (mean +/- SD) (controls, 164.5 +/- 20.1 g, NS); heart weight (HW), 0.499 +/- 0.084 g (controls, 0.448 +/- 0.035 g, NS); and HW/BW, 3.39 +/- 0.79 X 10(-3) (controls, 2.74 +/- 0.23 X 10(-3), p less than 0.05). The hemodynamic data under anesthesia were: HR, 378 +/- 42 (controls, 414 +/- 43, NS); LVSP, 108 +/- 16 mmHg (controls, 126 +/- 16, NS); LVDP, 4.0 +/- 4.8 mmHg (controls, 0.6 +/- 0.7, NS); LVEDP, 9.7 +/- 7.5 mmHg (controls, 3.4 +/- 1.4, NS); peak positive dp/dt, 4960 +/- 1431 mmHg/sec (controls, 6714 +/- 1326, p less than 0.05); (dp/dt)/DP40, 56.8 +/- 9.8 sec-1 (controls, 73.1 +/- 7.0, p less than 0.01); peak negative dp/dt, 3876 +/- 1072 mmHg/sec (controls, 4971 +/- 599, p less than 0.05); and time constant T of LV pressure fall, 7.7 +/- 1.3 msec (controls, 5.9 +/- 0.7, p less than 0.01). Five hamsters had congestion of the lungs and liver with or without an elevation of LVEDP. One of them had an organizing thrombus in the left atrium, and one had an aneurysm in the LV free wall. Though markedly varied in extent, residual myocardial fibrosis was always evident in the hearts in which isovolumic contractility and early diastolic relaxation of the LV were significantly impaired. In a clinical extension of these findings, it may be that some cases of dilated cardiomyopathy in man develop in a way similar to the pathological processes noted in this experiment.

Light- and electron-microscopic studies and immunohistochemical procedures were carried out on blood eosinophils and left ventricular endomyocardial biopsies from a 68-year-old man with an eosinophilia of 8.2 X 10(9)/l and congestive cardiac failure due to eosinophilic endomyocardial disease. Some blood eosinophils were vacuolated and degranulated, and reversal of the normal staining pattern of eosinophil granules was seen by means of electron microscopy. The biopsies showed degenerative changes in the cardiac myocytes, with interstitial fibrosis and infiltration by numerous eosinophils, mast cells, and macrophages. Eosinophils infiltrating the myocardium showed a decrease in the number of granules, many of which were indistinct or contained dissolving crystalloids, which occasionally were seen to be discharged onto the surface of adjacent cardiac myocytes. Immunohistochemical studies of the endomyocardial biopsies with a monoclonal antibody, which is specific for activated eosinophils and binds to the secreted forms of eosinophil cationic protein (ECP) and eosinophil protein-X (EP-X), demonstrated that the lesions contained numerous activated eosinophils and secreted ECP and EP-X. These findings support the concept that in eosinophilic endomyocardial disease, activated eosinophils infiltrate and degranulate in the myocardium, releasing eosinophil cationic proteins which then damage adjacent myocardial cells.

For the structural confirmation of FK-156, two possible structures, 1 and its geometric isomer 2, were synthesized. Di-Z-meso-diaminopimelic acid (4) was converted into 14 via a sequence of reactions involving, as key steps, an enzyme-mediated asymmetric hydrolysis (6 leads to 7), followed by carbobenzyloxylation using a copper chelate procedure (7 leads to 8). Condensation of 14 and the appropriately protected lactoyl dipeptide 17 and removal of the protecting groups of the resulting 18 afforded 1. Protection of 7 to 22, followed by coupling to glycine via an azide method, gave 25. Derivatization of 25 to 29 and condensation with 17 gave 30, which was deprotected to yield 2. Compound 1 proved to be identical in all respects with the natural product.