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To clarify the histopathological characteristics of pulmonary hypertension (PH) in Japan, and to clarify the role of serotonin and endclthelin in monocrotaline induced PH, human histopathologiical studies and experimental studies were carried out. An epidemiological study based on the Annual of the Pathological Autopsy Cases in Japan, and a morphological study on autopsy cases of congenital heart disease and idiopathic PH were performed. Plasma levels of serotonin and endothelin, vascular responsiveness to serotonin, and the effects of a selective serotonin antagonist, DV-7028, were investigated after monocrotaline injection. Plexogenic pulmonary arteriopathy was prevalent, and recurrent pulmonary thromboembolism and pulmonary veno-occlusive disease extremely rare among primary pulmonary hypertension in Japan. In secondary PH, systemic lupus erythematosus and mixed connective tissue disease were frequent and showedl particularly severe intimal and medial thickening. After an injection of monocrotaline, plasma serotonin and endotheliii levels were raised, and pulmonary arteries showed hyperreactivity to serotonin. DV-7028 (5-HT2 receptor antagonist) attenuated the rise in pulmonary artery pressure and the various effects of monocrotaline. There may be some genetic difference between PH in Japan and other countries. Roles far serotonin and endothelin in the initiation and progression of monocrotaline induced PH are suggested.

Angiogenesis is an indispensable process in the chronic proliferative synovitis and pannus formation of rheumatoid arthritis (RA). This study examined the expression of vascular endothelial growth factor (VEGF) isoforms and VEGF receptors, Flt-1, KDR and neuropilin-1, in RA and osteoarthritis (OA) synovia, and studied the relationship between their expression and the synovial angiogenesis. By RT-PCR analysis, the isoform VEGF(121) was constitutively expressed in all the RA (17/17 patients) and OA (8/8 patients) synovia. In contrast, the expression of the isoform VEGF(165) was observed in 41% of the RA synovia (7/17 patients), but was undetectable in the OA samples (0/8 patients). The receptor Flt-1 was almost constitutively expressed in RA (15/17 patients) and OA (8/8 patients) synovia, while the expression of KDR was detected in the synovia of six RA patients (6/17 patients; 35%) but none of the OA patients (0/8 patients). The expression of neuropilin-1, an isoform-specific receptor for VEGF(165) which enhances the binding of VEGF(165) to KDR, was also up-regulated in the same RA synovia that expressed KDR. Furthermore, there was a close correlation between the expression of isoform VEGF(165) and that of its receptors KDR and neuropilin-1. Morphometric analysis demonstrated that the vascular density is significantly higher in the RA synovial tissues with expression of VEGF(165), KDR, and neuropilin-1 than in those without their expression (p

Background The aim of the present study was to morphologically characterize the structure of the subepithelial blood vessels in the dark cell area of the human vestibular organs, and to determine whether immunocompetent cells such as macrophages and lymphocytes could be found around these small blood vessels. Materials and Methods All 31 surgical specimens (semicircular canals and utricles) were obtained from patients with vestibular schwannoma. Formalin fixed specimens were stained with hematoxylin and eosin (H&E), and with antibodies to von Willebrand Factor (vWF), leukocyte common antigen (LCA), and UCHL-1, and were examined with light microscope. Specimens fixed with glutaraldehyde were examined with a transmission electron microscope (TEM). Observations: Subepithelial blood vessels stained positive for vWF. By TEM observation, these blood vessels were observed to be capillaries that consisted of non-fenestrated endothelium, occasional pericytes, and a basement membrane. They were usually accompanied by melanophages with a number of secondary lysosomes containing phagocytosed degraded melanosomes and lipid droplets. Moreover, melanocytes and their cell processes directly surrounded these subepithelial capillaries. The fact that cells which were positively stained with LCA and UCHL-1 were present both in the intra- and subepithelial layer of the specimens, and that by TEM the intra- and subepithelial mononuclear cells with a lymphoid appearance had clustered dense bodies in their cytoplasm, suggested that they were a population of T lymphocytes. Conclusions Results suggested the possibility of a T lymphocyte-melanophage (macrophage) interaction, both originating from and harbored around subepithelial capillaries, which suggests the presence of an immune surveillance system in the human vestibular organs. Anat. Rec. 249:153–162, 1997. © 1997 Wiley-Liss, Inc.

An autopsy case of a 74-year-old man suffering from edema in the legs and diagnosed as protein-losing enteropathy due to intestinal lymphangiectasia is presented. He underwent a radical operation and radiotherapy for esophageal carcinoma at age 65 years and the onset of protein-losing enteropathy was at age 70. Postmortem examination disclosed widespread abnormalities of the duodenal and small intestinal lymphatics and mesenteric lymph node fibrosis. The mucosal lymphatic capillaries were markedly dilated. In the submucosal and serosal layers, the lymphatic vessels showed marked dilatation in some areas and fibrous occlusion with very thick muscle layers in others. All these lymphatic changes were presumed to be attributable to a reactive process secondary to lymph congestion, which it is suggested, was caused by the mesenteric lymph node fibrosis.

The autopsy findings in a 29-year-old male with Werner's syndrome are presented, with a review of similar data on 17 autopsy cases reported in the literature. The pathologic findings in this new case were scleroderma-like skin atrophy, arteriosclerosis, and atrophy of the endocrine glands (including the genital organs). In the reported cases of Werner's syndrome, as in the present example, the authors were unable to identify any responsible organ or system. However, they suggest that connective tissue, widely distributed throughout the entire body, may play an important role. The possible abnormal metabolism of connective tissue in Werner's syndrome deserves further study.

A characterisation of the biological behaviour of gastric carcinoma was attempted by relating the histological classification to the mean number of metastases for each case (metastatic index). The material was chosen from a consecutive series of 294 gastric cancer autopsies in which only conservative therapy had been given or in which the cancer was first diagnosed at autopsy. According to the extent of metastasis it was possible to divide the nine histological types into two groups of limited invasiveness and generalised invasiveness. Unfavourable biological behaviour of the cancer was determined by the presence of the latter group of histological types in the primary site even in cases where this histological type formed the minor component of the tumour. The variation in histology within the primary tumour and between the primary site and the metastatic sites was related both to histological affinities and to the metastatic index associated with the primary site histology. It is suggested that this dual classification system adds significantly to our understanding of the natural history of gastric cancer.

Prognosis of well-differentiated carcinoma of the thyroid gland is generally favorable, while that of anaplastic carcinoma, extremely poor. Well-differentiated carcinoma may sometimes be fatal; the most common underlying cause is considered to be due to anaplastic transformation of the original well-differentiated carcinoma to a less differentiated form. We studied 27 consecutive autopsy cases of fatal thyroid cancer treated at the Ito Hospital, Tokyo, during a five-year period, 1969-1973. We found uniform histological features of anaplastic carcinoma in 10 cases and of well differentiated carcinoma in four cases. In addition, co-existence of well-differentiated and anaplastic carcinomas was observed in nine cases and well differentiated and squamous cell carcinomas in four. Circumstantial evidence strongly suggests that malignant transformation is a part of the natural history of thyroid carcinoma, from well-differentiated carcinoma to less differentiated forms, either squamous cell or anaplastic carcinoma.

A case of hepatic infarction associated with terminal hemorrhagic necrotizing enteropathy (THNE) in an 84-year-old woman with cardiac failure is presented. The autopsy showed hepatic infarction, THNE, fibrous endocarditis, generalized arteriosclerosis, myocardial hypertrophy, liver congestion, and other findings as described. Both rare infarctions (hepatic and intestinal) seemed to have originated not only as a result of impaired systemic circulation due to cardiac failure, but also from liver congestion due to peripheral circulatory deficiency through the portal vein. The circulatory correlation between these infarcts of the liver and intestine is discussed.

Two autopsy cases of granulomatous aortitis associated with necrotizing angiitis and glomerulonephritis were reported. Case 1 was a 31 year-old female and a diagnosis of typical Takayasu's arteritis was made. Case 2 was a 64-year-old female. In the central portion of the aotlc media, granulomatous inflammation surrounding coagulation necrosis was observed. This aortitis is different from classical Takayasu's arteritis and is diagnosed as “unclassified” aortitis. The significance and inter-relationship of these lesions were discussed. Clinical and anatomical features of these two cases suggest some common background of Immune abnormalities.

A case of annulo-aortic ectasia was reported. The patient was a 44 year old Japanese female who expired shortly after the operative intervention against aortic aneurysm and aortic insufficiency. This is the first case of annulo-aortic ectasia reported in Japan. Histological findings of the resected aneurysm revealed pronounced cystic medial necrosis. At autopsy, similar medial necrosis was found in the remaining aorta, pulmonary artery and some of the major branches of the aorta. The aortic valve cusps also showed myxomatous accumulation of acid mucopolysaccharides and hypoplasia of annular connective tissue. The aortic ring was dilated with evidence of regurgitation. Problems related to pathologic findings were discussed with special reference to a forme fruste manifestation of Marfan's syndrome. We believe cases, such as presented here, should not be considered as a forme fruste of Marfan's syndrome with the present knowledge of the disease, in spite of the morphologic similarity of lesions in our case with those described in classical Marfan's syndrome.