Yoshihiro Hamashima

Quantitative analysis of narrowings of intramyocardial small arteries in normal hearts, hypertensive hearts, and hearts with hypertrophic cardiomyopathy.

To clarify the pathophysiologic role of intramyocardial small artery (IMSA) diseases in hypertrophied hearts, narrowings of the IMSA were quantitatively evaluated in 39 autopsied hearts, 10 from patients with typical hypertrophic cardiomyopathy (HCM), four from patients with HCM showing features mimicking dilated cardiomyopathy (DCM-like HCM), 10 from patients with hypertension, and 15 from normal adults. The relations of narrowings of the IMSA to myocytic hypertrophy, myocardial fiber disarray, and fibrosis were also examined. The external caliber and the ratio of the luminal area to the total vascular area (percent luminal area, % lumen) were calculated by an image analyzer in 85 to 203 IMSAs from each patient. The external calibers of the IMSAs were similar among groups of hearts with HCM, hypertensive hearts, and normal hearts but were greater in those with DCM-like HCM. The mean % lumen of the IMSAs was similarly reduced in the hearts with HCM (29 +/- 5% in the ventricular septum and 31 +/- 5% in the left ventricular free wall) and in hypertensive hearts (30 +/- 8% and 31 +/- 7%) compared with that in normal hearts (40 +/- 5% and 38 +/- 5%) and was the lowest in the ventricular septum of hearts with DCM-like HCM (17 +/- 3%). The mean % lumen of the IMSA was inversely correlated with heart weight (r = -.59), the mean size of myocytes (r = -.66 in the ventricular septum, r = -.63 in the free wall), and percent fibrotic area in the septum (r = -.68). The mean % lumen values of the IMSAs in the tissues with and without disarray in the hearts with HCM were similar. Thus IMSA disease is of pathophysiologic importance in patients with HCM, DCM-like HCM in particular, or with hypertension.

Dermatopathological studies on skin lesions of MRL mice

SummaryThe MRL-lpr/lpr(MRL/l) mouse is a new animal model for human systemic lupus erythematosus (SLE) and skin lesions with hair loss and scab formation are one of the characteristic manifestations in this mouse. We investigated the histopathology of the skin lesions in MRL/l mice and studied the related autoimmune phenomenon. Light microscopical observations revealed hyperkeratosis, acanthosis, hypergranulosis, liquefaction, vasodilation in the dermis and T-cell infiltration into the dermis at the age of 5 months (mo). Immunohistological studies showed the presence of immunoglobulins and/or complement depositions at the dermal-epidermal junction (DEJ). In some mice there was deposition of immunoglobulin at the DEJ at 2 mo and in 90%–100% of MRL/l mice at over 5 mo. Temporal relationship was present among cutaneous immunoglobulin depositions, the occurrence of anti-DNA antibodies and proteinuria. These findings suggest that MRL/l mice might provide a new aid for studying the biological mechanisms of the development of skin lesions in human SLE.

General Pathology Of Kawasaki Disease

Systemic pathological alterations were studied in thirty‐seven autopsied patients with Kawasaki disease. Systemic vasculitis was the most characteristic pathological finding and was present in all the patients. In addition to the vasculitis, there was a high incidence of inflammatory lesions in various organs and tissues: in the heart, endocarditis, myocarditis, and pericarditis; in the digestive system, stomatitis, sialoduct‐adenitis, catarrhal enteritis, hepatitis, cholangitis, pancreatitis, and pancreas ductitis; in the respiratory system, bronchitis and segmental interstitial pneumonia; in the urinary system, focal interstitial nephritis, cystitis, and prostatitis; in the nervous system, aseptic leptomeningitis, choriomeningitis, ganglionitis, and neuritis; in the hematopoietic system, lymphadenitis, splenitis, and thymitis. Dermatitis, panniculitis or myositis were also observed in some patients. Therefore, Kawasaki disease is a systemic inflammatory disease which mainly affects the cardiovascular system. These systemic inflammatory lesions are considered to correspond to the variegated clinical manifestaitions. The relationship between Kawasaki disease and infantile polyarteritis nodosa (IPN) were discussed, based on the clinicopathological characteristics.

Morphological observations on the vasculitis in the mucocutaneous lymph node syndrome

Twenty-seven skin biopsies were obtained from the exanthemata of patients in the acute stage of the mucocutaneous lymph node syndrome (MCLS). The three vascular systems of different caliber size—the intrapapillary capillary loops (ICL), the superficial arteriolar or venular plexus (SAP, SVP) and the small subcutaneous vessels—were examined to investigate the characteristics of the vasculitis in MCLS and differentiate it from infantile polyarteritis nodosa (IPN). Significant papillary edema and dilatation of ICL, SAP and SVP were observed on the 4th day after the onset of the illness, and then gradually decreased. In the subcutaneous regions, vasculitis began which endothelial necrosis, and subendothelial edema and degenerative changes in the muscle cells followed. These changes in the small subcutaneous vessels were observed for a longer period than in the ICL, SAP and SVP. Moderate mononuclear cell infiltrations were observed. Both arteries and veins were affected.

A clinicopathologic study of patients with hemorrhagic myocardial infarction treated with selective coronary thrombolysis with urokinase.

Hemorrhagic acute myocardial infarction (AMI) was studied after selective intracoronary thrombolysis (SICT) in 30 patients undergoing autopsy. Urokinase, 240,000 to 1,200,000 U, was selectively injected into the infarct-related coronary artery at 2 to 9 hr (4 +/- 2 hr) after the onset of AMI. The infarct-related coronary artery showed complete occlusion in 21, 99% stenosis in eight, and 90% stenosis in one patient before SICT. After SICT, complete occlusion was seen in only five, 99% stenosis in 22, and 90% stenosis in three patients. Twenty-eight patients had transmural infarction and the other two had subendocardial infarction. Macroscopically and microscopically, the degree of hemorrhage was classified as no, slight, moderate, or marked bleeding and the hemorrhagic infarction was defined as moderate or marked diffuse bleeding in the infarct area. According to the interval from SICT to death, patients were also classified into stage I (early acute stage, 1 to 4 hr after SICT and 4 to 13 hr after the onset of AMI; n = 7), stage II (late acute stage, 9 hr to 11 days after SICT and 15 hr to 11 days after the onset of AMI; n = 18), or stage III (old infarction stage, over 17 days after AMI and SICT; n = 5). There were no significant differences with respect to the frequency of recanalization, the time from the onset of AMI to SICT, the dose of urokinase, or other clinical parameters among patients at the three stages. Only the hearts of patients in stage II showed hemorrhagic infarction, and it was found in 15 of 18 of these hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative analysis of infarct size, contraction band necrosis, and coagulation necrosis in human autopsied hearts with acute myocardial infarction after treatment with selective intracoronary thrombolysis.

To assess the importance of contraction band necrosis (CBN) in patients with acute myocardial infarction (AMI) treated with selective intracoronary thrombolysis, CBN, coagulation necrosis, and infarct size (expressed as CBN + coagulation necrosis) were analyzed quantitatively in 16 autopsied hearts. Intracoronary thrombolysis was performed from 2 to 6 hr after the onset of AMI, and the time from the onset of AMI to death was 7 to 168 hr. Cineangiography revealed no evidence of good collateral circulation in any of the patients. The 16 patients were classified into three groups: six patients with successful thrombolysis (100% to 99% stenosis, group I), five patients with unsuccessful thrombolysis (100% to 100%, group II), and five patients with 99% stenosis before thrombolysis (group III). Among the three groups, there were no significant differences in the time from the onset of AMI to thrombolysis, the time from the onset of AMI to death, the cause of death, or the degree of collateral circulation. The percentage of the risk area involved by the infarct in group I (82 +/- 6%) was similar to that in group II (80 +/- 11%). Infarct size was not reduced in group I because collateral circulation was not good and because the degree of recanalization after thrombolysis was 1%. However, the percentage of the infarct area with CBN was significantly higher in group I (20 +/- 9%) then in group II (3 +/- 3%). This finding shows that diffuse CBN occurred after reperfusion in patients with AMI treated with thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinicopathologic study of abnormal Q waves in Kawasaki disease (mucocutaneous lymph node syndrome): An infantile cardiac disease with myocarditis and myocardial infarction☆

Abstract A correlative study of abnormal Q waves and pathologic findings was performed on 15 hearts from children with Kawasaki disease. Gross pathologic study revealed acute angiitis with pericarditis, acute myocarditis and coronary heart disease as the result of angiitis. Three hearts in infants with abnormal Q waves in leads I and aVL and chest leads had gross transmural fibrosis in the anteroseptal-lateral walls of the left ventricle. Coagulation necrosis (acute myocardial infarction) or fibrosis, or both, in more than 30 percent of the wall thickness in the posterior ventricular wall was found in four of five hearts in infants with abnormal Q waves in leads II, III and aVF. Seven of the 15 infants had no abnormal Q waves, and only 2 of the 7 had myocardial damage in over 30 percent of the wall thickness. In 9 of the 15 hearts there were 11 gross areas of fibrosis; in these hearts there was a corresponding severe stenosis of more than 90 percent due to organization in the major coronary arteries supplying these areas. In three hearts with coagulation necrosis, the coronary occlusion was caused by fresh large thrombi. In the six hearts without sizable fibrosis, the grade of stenosis due to organization was less than 75 percent in each of the major coronary arteries. Coronary aneurysm due to angiitis was seen in 12 of the 15 hearts, and at autopsy fresh large thrombi were seen in each aneurysm. Ten of the 12 hearts exhibited sizable areas of myocardial damage. Three hearts without aneurysm manifested angiitis with mild stenosis of less than 25 percent, but there were no macroscopic fresh thrombi in any of the major coronary arteries. Thus, abnormal Q waves in children with Kawasaki disease almost always reflect myocardial damage in over 30 percent of the wall thickness of the left ventricle. Electrocardiograms are useful to determine the anterior or posterior localization of the damage. Nevertheless, the possibility of transmural and nontransmural areas of damage cannot be excluded in the absence of abnormal Q waves.

Distribution of collagen type IV in soft tissue tumors: An immunohistochemical study

The distribution of collagen type IV, one of the major constituents of basement membrane, was studied immunohistologically in a series of 103 soft tissue tumors including those of peripheral nerve origin, smooth muscle origin, striated muscle origin, fibrous tissue origin, fibrohistiocytic origin, adipose tissue origin, synovial tissue origin, and blood vessel origin, paragangliomas, alveolar soft part sarcomas, granular cell tumors, and epithelioid sarcomas. Intensely positive staining for collagen type IV was observed in neurilemomas, neurofibromas, malignant schwannomas, and blood vessel tumors. Weakly to moderately positive staining was seen in leiomyomas, angiomyomas, and leiomyosarcomas. In contrast, synovial, fibroblastic and fibrohistiocytic tumors, benign or malignant, were negative. In paragangliomas, granular cell tumors, and alveolar soft part sarcomas, positive staining was evident surrounding nests or clusters of tumor cells. In all tumors, staining for collagen type IV clearly illustrated the vascular pattern. Cancer 58:269–277, 1986.

Relationship between Secretory IgA, IgA-Containing (C3-Fixing) Circulating Immune Complexes, and Complement Components (C3, C4) in Patients with Obstructive Jaundice

Serum secretory IgA, IgA-containing circulating immune complexes (IgA-CIC), complement components, and major immunoglobulins were measured in patients with biliary tract stones and/or tumors of the biliary tract or pancreas. The levels of secretory IgA and total IgA were increased in patients with and without obstructive jaundice. The levels of both C3 and C4 were significantly higher in patients with or without obstructive jaundice than in healthy controls. In patients with obstructive jaundice the increased levels of secretory IgA, total IgA, and IgA-CIC were correlated with the increase of C3 but not with that of C4.

Number and size of myocytes and amount of interstitial space in the ventricular septum and in the left ventricular free wall in hypertrophic cardiomyopathy

Abstract The wall thickness of the myocardium depends on 3 variables: the number of muscle layers, the mean size of myocytes and the percent area of interstitial space. To clarify the pathogenesis of asymmetric septal hypertrophy (ASH) in hypertrophic cardiomyopathy (HC), these 3 variables and wall thickness were measured in the ventricular septum (VS) and in the left ventricular (LV) posterior wall. The VSLV ratio of wall thickness was correlated with the VSLV ratios of the 3 variables in the hearts of 10 patients in HC with ASH and in 37 control patients without ASH (25 with no cardiac disease and 12 with systemic hypertension). The VSLV ratios (mean ± standard deviation) in hearts with HC were 1.6 ± 0.2 for wall thickness, 1.8 ± 0.3 for the number of transmural muscle layers, 0.9 ± 0.1 for mean size of myocytes and 1.1 ± 0.1 for percent area of transmural interstitial space. The VSLV ratios in control hearts were 1.0 ± 0.1 for wall thickness, 1.0 ± 0.1 for number of transmural muscle layers, 1.0 ± 0.1 for mean size of myocytes and 1.0 ± 0.1 for percent area of interstitial space. The VSLV ratios of wall thickness and transmural muscle layers correlated well. In hearts with ASH in HC, the number of muscle layers was greater in the VS (630 ± 80) and smaller in the LV free wall (360 ± 70) than in the control hearts (500 ± 60 and 480 ± 50, respectively). Thus, the pathogenetic factor of ASH in HC is an increased VSLV ratio of the number of muscle layers, and the degree of ASH is determined by the combined abnormalities in the numbers of transmural muscle layers in the VS and the LV free wall.