HISTOPATHOLOGIGAL STUDY OF HYPERTROPHIC CARDIOMYOPATHY WITH PROGRESSION TO LEFT VENTRICULAR DILATATION

The heart of seven cases of fatal congestive heart failure with dilated left ventricle, developing in 5 patients with symptomatic hypertrophic cardiomyopathy (HCM) and 2 patients with histologically widespread disarray of both ventricles, was morphologically investigated. These 7 cases showed myocardial widespread disarray and massive fibrosis, the mean percent area of fibrosis was 40.6% and 59.4% at upper and lower levels of left ventricles, respectively. Fibrosis was most extentsive in the lateral wall, and followed by anterior, posterior and interventricular walls. The severity of cell infiltration in left ventricle was completely matched to that of fibrosis and was most extensive in subepicardial area followed by middle and subendocardial areas of left ventricle. The intima and medial thickness of intramural small arteries in the fibrotic areas was significantly larger (p<0.05) than that of nonfibrotic areas, which suggested that the effect of intramural small artery was not essential for pathogenesis of massive fibrosis. ACTA PATHOL. JPN. 37: 1041 -1052, 1987.     

Pulmonary hypertension due to tumor emboli: A report of three autopsy cases with morphological correlations to radiological findings

Three cases of pulmonary hypertension caused by tumor emboli to the lungs are described. Two of the three cases had a clinical diagnosis of pulmonary thromboembolism until surgical embolectomy, and the other had a diagnosis of primary pulmonary hypertension. Autopsy disclosed chondrosarcoma, choriocarcinoma and gastric cancer as the primary tumors, respectively. Pulmonary vascular obstruction due to tumor embolism leading to pulmonary hypertension is a previously rare clinical entity, and obstructed pulmonary vessels are believed to tend to be small vessels. We compared the autopsy and radiological findings and concluded that pulmonary tumor embolism involved not only the small peripheral arteries but also the segmental and/or lobar arteries.     

Expression of matrix Gla protein and osteonectin mRNA by human aortic smooth muscle cells.

BACKGROUND: Recent data indicate that matrix proteins such as matrix Gla protein (MGP) and osteonectin (ON) influence not only mineralization of vasculature but smooth muscle cell (SMC) differentiation. METHODS: We examined whether MGP and ON are expressed by human aortic SMCs in vivo using Northern blotting, in situ hybridization and immunohistochemistry. RESULTS: MGP and ON mRNAs were strongly expressed in the aorta without atherosclerosis from newborn and four young subjects up to 10 years old. In the aorta from 15 adult cases, MGP and ON mRNAs were decreased as atherosclerosis developed. We determined cell type and distribution of the MGP- and ON mRNA-expressing cells by in situ hybridization and immunohistochemistry. In the aorta obtained from newborn and young subjects, SMCs in the media and thin intima expressed MGP mRNA and, to a lesser extent, ON mRNA. In the adult aorta with fibrous thickening, MGP mRNA was expressed by intimal SMCs and subpopulation of medial SMCs. Osteonectin mRNA was expressed mainly by intimal SMCs and few medial SMCs. Double immunohistochemical staining revealed that both MGP- and ON protein-expressing cells were positive for anti-alpha-smooth muscle actin antibody, aortic SMCs. CONCLUSIONS: These results suggested that MGP and ON expression by aortic SMCs might be regulated by the degree of atherosclerosis and SMC differentiation in human aorta.     

Anti-KANNO: A Novel Alloantibody Against a Red Cell Antigen of High Frequency

We encountered a broadly reactive red cell alloantibody in 1991, reacting unlike any other known antibody, and named it anti-KANNO after the first patient. A total of 28 cases of anti-KANNO in the Japanese literature were reviewed. To distinguish KANNO from other antibodies against high-frequency antigens, including anti-JMH, anti-Ch/Rg, and anti-Jr^a, we conducted serologic studies with proteolytic enzyme and chemical treatments, complement sensitization against red cells, and serum neutralization techniques. Reactivity of anti-KANNO against red cells lacking high-frequency antigens and antisera to high-frequency antigens against KANNO cells were tested. Among the 28 patients, 26 were female, of whom 25 had a history of pregnancy. Red cells from patient KANNO were reactive with antisera against antigens of high frequency. Anti-KANNO reacted weakly with all cells known to lack high-frequency antigens. It reacted with 2-aminoethylisothiouronium bromide, so it can be distinguished from anti-JMH. Differences among anti-KANNO, anti-Ch/Rg, and anti-Jr^a emerged with enzyme-treated cells, complement-sensitized cells, and the addition of normal serum. As yet, there are no reports of hemolytic transfusion reaction or hemolytic disease of the fetus and newborn attributable to anti-KANNO. It appears that anti-KANNO is a newly characterized antibody more likely stimulated by pregnancy than by transfusion and with little or no clinical significance. Further surveillance and investigation of anti-KANNO, its antigen biochemistry, and its genetics are warranted.     

Application of real-time RT-PCR to quantifying gene expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human abdominal aortic aneurysm

BACKGROUND: The relative expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), key regulators in remodeling of extracellular matrix, are considered to play a pivotal role in the development of abdominal aortic aneurysm (AAA). However, few data exist regarding quantitative assessment of their expression in clinical settings. METHODS: In 22 patients with AAA who underwent graft replacement, tissue samples of the AAA and non-dilated aorta were obtained. Using a real-time RT-PCR method that enabled quantitative measurement of mRNA levels in small tissue samples, we determined gene expression levels of MMPs and TIMPs relative to that of glutaraldehyde 3-phosphate dehydrogenase in each sample. RESULTS: The expression levels of the MMP-1 and -3 genes were significantly augmented in AAA compared with non-dilated regions (4.48 +/- 2.01 versus 0.26 +/- 0.12, P < 0.01 and 1.89 +/- 1.00 versus 5.01 +/- 0.97, P < 0.05, respectively). Although genes for TIMP-1, -2 and -3 tended to be upregulated in AAA, relative expression levels of MMP-1 to TIMP-1, MMP-1 to TIMP-2, MMP-1 to TIMP-3, and MMP-3 to TIMP-2 were still higher in AAA than in non-dilated regions (1.12 +/- 0.63 versus 0.10 +/- 0.03, 4.13 +/- 1.12 versus 0.43 +/- 0.11, 1.61 +/- 0.59 versus 0.14 +/- 0.03, and 7.81 +/- 1.60 versus 2.56 +/- 0.76, respectively, P < 0.05). CONCLUSION: These results demonstrate that the present real-time RT-PCR method is reliable for the determination of mRNA levels in small samples of vascular tissue and that disproportional expression of both MMP-1 and MMP-3 relative to TIMPs relates pathologically to the evolution of AAA.