The human renal lymphatics under normal and pathological conditions.

AIMS: The renal lymphatics have not been fully documented in humans. The aim of this study was to clarify the morphology of the human renal lymphatic system under normal and pathological conditions by immunohistochemistry using anti-D2-40 antibody. METHODS AND RESULTS: Normal and pathological renal tissues obtained at autopsy as well as nephrectomy specimens with renal cell carcinoma (RCC) were used. Thin sections were immunostained with antibodies against D2-40 and CD31. In normal kidney, D2-40+ lymphatics were abundant in the interstitium around the interlobar and arcuate arteries/veins but sporadic in those around the glomeruli or between the tubules in the cortex. A few lymphatics contained erythrocytes in their lumina. Lymphatics were seldom present in the medulla. In RCC cases, lymphatics were evident at the tumour margin, whereas CD31+ capillaries were abundant throughout the tumour and lymphatics were increased in the fibrous interstitium around the tumour. Lymphatic invasion by RCC cells was also detectable. D2-40+ lymphatics were evident in other pathological conditions and end-stage kidney had a denser lymphatic distribution than normal kidney. CONCLUSIONS: Lymphatics are abundant around the arteries/veins and are also present in the renal cortex and medulla. D2-40 immunostaining is helpful for investigating the pathophysiological role of renal lymphatics.

Follicular bronchiolitis associated with Legionella pneumophilia infection.

An 8-month-old girl with respiratory distress and stridor was admitted to our hospital. Two days later, she died of respiratory insufficiency due to pneumonia. Autopsy confirmed the presence of follicular bronchiolitis (FBB) in both lungs. After consideration of her clinical course, we focused on three pathogens: Legionella pneumophilia, Pneumocystis carinii, and Mycobacterium tuberculosis. Only Legionella pneumophilia was detected by both immunohistochemistry and polymerase chain reaction.

Follicular bronchiolitis (FBB) associated with Legionella pneumophilia infection.

An 8-month-old girl with respiratory distress and stridor was admitted to the authors' hospital. Two days later, she died of respiratory insufficiency due to pneumonia. Autopsy confirmed the presence of follicular bronchiolitis (FBB) in both lungs. After considering her clinical course, the authors focused on three pathogens: Legionella pneumophilia, Pneumocystis carinii, and Mycobacterium tuberculosis. Only Legionella pneumophilia was detected by both immunohistochemistry and PCR.

The distribution and production of cholesteryl ester transfer protein in the human aortic wall.

Cholesteryl ester transfer protein (CETP) has been considered to mediate the transfer of cholesteryl ester from arterial wall, however, the distribution and production of CETP in human arterial wall remains unclear. Present study histopathologically demonstrated the distribution of CETP and CETP mRNA in the human aortic wall by immunohistochemistry and in situ hybridization. While CETP was constantly distributed in the media, the protein was recognized within the intima with fibrocellular thickening and atherosclerotic intima. Double immunostaining methods demonstrated CETP expression in smooth muscle cells in the intima and media. CETP mRNA was detected not only in intimal cells but medial smooth muscle cells. Intimal cells expressing CETP mRNA were considered to be monocyte-derived macrophages and smooth muscle cells by immunohistochemistries using two antibodies against smooth muscle actin and human macrophage on the subserial sections. Our in vivo study provides that CETP is produced by smooth muscle cells in the intima and media of human aorta, and it is suggested that arterial smooth muscle cells positively participate in the removal of excessive cholesteryl ester from the arterial wall by CETP production.

One hundred consecutive treatments with holmium: YAG laser for pulmonary bullae: especially in conjunction with gelatin-resorcinol formaldehyde-glutaraldehyde glue adhesion.

BACKGROUND AND OBJECTIVE: We have widely used a Ho:YAG laser to treat bullae thoracoscopically. STUDY DESIGN/MATERIALS AND METHODS: Bullae with broad necks were treated with a Ho:YAG laser thoracoscopically. Because one patient relapsed after application of fibrin glue in the early period, a DEXON (polyglycolic acid) mesh patch soaked in fibrin glue was used through a 2-cm opening in the subsequent cases. Lastly, gelatin-resorcinol formaldehyde-glutaraldehyde (GRFG) glue was applied through a 5-mm opening instead of a DEXON mesh after coagulation. RESULTS: In the 38 patients patched with DEXON mesh soaked in fibrin glue and 56 patched with GRFG glue after coagulation, none relapsed. CONCLUSION: Combined uses of fibrin glue plus DEXON mesh or GRFG glue were effective when bullae were treated with the Ho:YAG laser. However, the wound was smaller and more cosmetic in the GRFG glue group than in the DEXON mesh plus fibrin glue group.

The effect of myocardial bridging of the coronary artery on vasoactive agents and atherosclerosis localization.

The relationship between alterations in the immunohistochemical expression of three vasoactive agents [endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), and angiotensin-converting enzyme (ACE)] and the occurrence human atherosclerosis was investigated in relation to the myocardial bridge (MB) of the left anterior descending coronary artery (LAD), an anatomical site that experiences increased shear stress. Five millimetre cross-sections of LADs with MB from 22 autopsied cases were taken from the left coronary ostium to the cardiac apex and were immunohistochemically stained with antibodies against eNOS, ET-1, and ACE. The extent of atherosclerosis in each section was calculated using the atherosclerosis ratio (intimal cross-sectional area/medial cross-sectional area) determined by histomorphometry. The results were analysed according to their anatomical location relative to the MB, either proximal, beneath, or distal. The extent of atherosclerosis was significantly lower beneath the MB, compared with proximal and distal segments. The expression of eNOS, ET-1, and ACE was also significantly lower beneath the MB. The expression of these agents correlated significantly with the extent of atherosclerosis. Because nitric oxide, after its production by eNOS, is believed to be degraded by superoxide radicals, the effect of eNOS expression on atherosclerosis remains controversial. However, the present findings clearly indicate that the expression of ET-1 and ACE is directly related to the development of human coronary atherosclerosis in vivo through shear stress.

[Renal cell carcinoma metastatic to the ovary: a case report].

A 47-year-old woman underwent left radical nephrectomy in 1995, and pathological diagnosis showed a primary renal cell carcinoma with clear cell subtype. Four years later on her routine checkup, abdominal computerized tomography revealed a 9-cm of predominantly solid and partially cystic tumor in the pelvic cavity. The patient was referred to Gynecologic Department and a total hysterectomy with bilateral salpingo-oophorectomy was subsequently performed under the diagnosis of a left ovarian tumor. A cut surface of the solid component of the tumor was macroscopically yellowish. Pathological examination revealed alveolar growth of tumor cells with abundant clear cytoplasm including fat components. In some areas of the tumor, there were patterns of tubular structures which were cystically dilated. The typical findings usually found in the primary ovarian clear cell adenocarcinoma were absent in the tumor, and the final pathological diagnosis was left ovarian metastasis of renal cell carcinoma. The ovarian metastasis of renal cell carcinoma is quite rare and to our knowledge only eleven cases were reported in the past 20 years. We report on a case and review the literature.

Sequential changes in localization of repair-related proteins (heat shock protein 70, ubiquitin and vascular endothelial growth factor) in the different stages of myocardial infarction.

AIMS: The myocardium expresses vascular endothelial growth factor (VEGF), heat shock protein 70 (HSP70), and ubiquitin immediately after the onset of cardiac ischaemia. This study demonstrated the sequential changes in localization of these proteins, in addition to fibronectin and troponin T (TnT), in human hearts with myocardial infarction (MI). METHODS AND RESULTS: Myocardial tissues from 40 autopsied MI cases were immunostained with the five antibodies against VEGF, HSP70, ubiquitin, fibronectin and TnT. Fibronectin was recognized only in the cardiomyocytes with infarction. Although TnT, HSP70, ubiquitin and VEGF were detected in the affected myocardium in the early stages, their expression in cardiomyocytes around infarcted foci were more intense. The cardiomyocytes with coagulative myocytolysis were positive for fibronectin, but negative or weakly positive for TnT, HSP70, ubiquitin and VEGF. In contrast, the cardiomyocytes with colliquative myocytolysis were strongly positive for TnT, HSP70, ubiquitin and VEGF, but negative for fibronectin. CONCLUSIONS: Immunostaining using antibodies to fibronectin, TnT, HSP70, ubiquitin and VEGF is useful for the discrimination between infarcted myocytes and ischaemia-damaged myocytes in the human heart with MI at autopsy.

Collagen alteration in vascular remodeling by hemodynamic factors.

The collagen alterations in the vascular wall remodeled by hemodynamic change were investigated by electron microscopy and immunohistochemistry. The left anterior descending coronary artery (LAD) without a myocardial bridge (MB) showed both lower matrix metalloproteinase-1 (MMP-1) expression and a smaller extent of spiraled collagen (SC) distribution than the LAD wall with MB, in which the intima was influenced by high shear stress. In the wall of the varicose great saphenous vein (GSV) the expression of MMP-1 was lower, while the expression of prolyl 4-hydroxylase was higher, than in the normal GSV. The extent of SC distribution in the intima and media of the varicose GSV was smaller than that in the normal GSV. An analogous difference in results was demonstrated between the portal vein (PV) of patients with liver cirrhosis and normal PV. However, the levels of expression of MMP-2, MMP-9 and tissue inhibitors of MMP (TIMPs) in these pathologic vessels were not different from those in the corresponding normal vessels. The results indicate that hemodynamic forces such as shear stress and increased intravascular blood pressure contribute to the collagen alterations in the vascular wall, which may lead to vascular wall remodeling.

Enhanced expression of caspase-3 in hypertrophic scars and keloid: induction of caspase-3 and apoptosis in keloid fibroblasts in vitro.

Recent studies have suggested that the regulation of apoptosis during wound healing is important in scar establishment and development of pathological scarring. To examine the phenomenon of apoptosis and its involvement in the process of pathological scarring, we immunohistochemically quantified differential levels of expression of caspase-3 and -2, which are activated during apoptosis in vitro, in surgical resected scar tissues. We divided 33 cases of normally healed flat scars and 18 cases of pathological scars (15 cases of hypertrophic scars and 3 cases of keloid) into three groups (S1 = <10 months' duration; S2 = 10 to 40 months' duration; and S3 = >40 months' duration) according to the duration of scar. In all three groups examined, the semiquantitative scores for caspase-3 staining were significantly higher for the combination of hypertrophic scars and keloid as a group compared with normally healed flat scars, suggesting reduced cell survival and increased apoptotic cell death in hypertrophic scars and keloid. Apoptosis and caspase proteolytic activities were examined in vitro using two flat scar-derived fibroblast lines (FSFB-1 and -2) and two keloid-derived fibroblast lines (KFB-1 and -2). After 24 hours of serum deprivation, apoptotic cells were significantly increased in both KFB lines, whereas serum deprivation of FSFB-1 cells did not result in a significant increase in apoptotic cell number. After serum deprivation, significant increases in caspase-3 proteolytic activities were detected in both KFB lines compared with both FSFB lines. In contrast, no significant differences with caspase-8 activity were observed between similarly treated KFB and FSFB lines. Furthermore, serum deprivation-induced apoptosis of KFB-2 cells was significantly inhibited by the caspase-3 inhibitor Ac-Asp-Glu-Val-Asp-fluoromethyl ketone (DEVD-FMK), indicating that caspase-3 is important for serum deprivation-induced apoptosis in KFB-2 cells. Considering the role of caspase-3 as a key effector molecule in the execution of apoptotic stimuli, our results suggested that enhanced expression of caspase-3 in hypertrophic scars and keloid induces apoptosis of fibroblasts, which may play a role in the process of pathological scarring.

Moyamoya disease with concurrent von Recklinghausen's disease and cerebral arteriovenous malformation.

We present a rare autopsy case of von Recklinghausen's disease with Moyamoya vessels and arteriovenous malformation. A 58-year-old female patient suffered from dysarthria and dysphagia. On examination, Parkinson's signs, pseudobulbar palsy, and muscular weakness of the left extremity and pyramidal tract signs were observed. An enhanced brain computed tomography revealed abnormal high-density network vessels at the thalamus and midbrain. By cerebral angiography, the following changes were observed; occlusion of the right internal carotid artery at the bifurcation, and abrupt narrowing and occlusion of the left internal carotid artery at the bifurcation and siphon. A lateral vertebral arteriography revealed telangiectasia at the basilar tip. The patient died of pulmonary thromboembolism at age 61. The vessels of the circle of Willis were hypoplastic. The optic nerves, infundibulum and mammillary body were covered with a large number of ectastic vessels. Arteriovenous malformations were observed in the bilateral occipital lobes. Histopathologically, the elastic lamina of Moyamoya vessel was conspicuously wavy and often duplicated or triplicated, and discontinued occasionally. Discontinuity of the elastic lamina of the perforating arteries and circumferential arteries supplied by the middle cerebral artery (MCA), anterior CA (ACA) and posterior CA (PCA), was also occasionally observed. It is likely that the Moyamoya vessels in this patient were compensatorily formed by congenital hypoplasia of the internal artery, MCA, ACA and PCA.

Effects of aminoguanidine on serum advanced glycation endproducts, urinary albilmin excretion, mesangial expansion, and glomerular basement membrane thickening in Otsuka Long-Evans Tokushima fatty rats.

This study evaluated the effects of treatment with an inhibitor of advanced glycation endproducts, aminoguanidine, on the development of albuminuria, mesangial expansion and glomerular basement membrane (GBM) thickening in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which we found to be an excellent model of non insulin-dependent diabetes mellitus (NIDDM), for its very close similarity to human NIDDM. OLETF rats were randomized into a non-treatment diabetic group (D-group, n = 5) and an aminoguanidine-treated group (AG-group, n = 5). The AG-group was given 100 mg/dl aminoguanidine HCl in free drinking water. Treatment was started at 16 weeks of age. We measured body weight, plasma glucose, total cholesterol, triglycerides and the urinary albumin excretion (UAE) rate before and after treatment at regular intervals. At 56 weeks of age, we measured serum advanced glycation endproducts (AGE), mesangial expansion and glomerular basement membrane. There were no significant differences in pre-treatment body weight, plasma glucose and UAE between the D-group and the AG-group. Likewise, after treatment there were no significant differences in body weight, plasma glucose, total cholesterol, triglycerides and immunoreactive insulin. Significant differences were, however, noted in serum AGE (63.2 +/- 3.5 and 51.8 +/- 3.0 U AGE/ml, P < 0.05), UAE (203.6 +/- 37.7 and 89.8 +/- 18.6 mg/day, P < 0.05), fractional mesangial volume (21.3 +/- 1.7 and 16.7 +/- 0.8%, P < 0.05) and GBM thickness (453 +/- 17 and 366 +/- 50 nm, P < 0.05) between the D-group and the AG-group. Our results suggest that aminoguanidine inhibits the AGE formation and the development of diabetic nephropathy in OLETF rats.

Concurrent pulmonary arterial dissection and saccular aneurysm associated with primary pulmonary hypertension.

We report concurrent pulmonary arterial dissection and saccular aneurysm resulting from primary pulmonary hypertension in a 26-year-old man. The pulmonary trunk was dissected 9 cm along its entire circumference, 3 cm above the pulmonary valvular cusps. In addition, a saccular aneurysm 3.5 cm in diameter had formed at the right pulmonary hilus. Histopathology revealed marked medical degeneration and fragmentation of the elastic laminae in the former lesion and a true aneurysm with attenuation and fragmentation of elastic laminae in the latter. The peripheral vasculature in the lungs showed evidence of increased pulmonary arterial pressure, including plexiform and angiomatoid lesions. We present this unique case and discuss the pathomorphogenesis of these lesions in conjunction with primary pulmonary hypertension.

Myocardial ischemia due to vascular systemic amyloidosis: a quantitative analysis of autopsy findings on stenosis of the intramural coronary arteries.

A case is reported of a 65 year old man who suffered myocardial ischemia resulting from extensive stenosis of the intramural coronary arteries secondary to systemic vascular involvement by primary amyloidosis. In the myocardium, there were multiple fibrotic foci scattered mainly in the subendocardial region of the ventricle. Intramural coronary arteries were stenotic or occlusive due to amyloid-induced luminal narrowing, but there was no significant stenosis of the epicardial coronary arteries. Quantitative analysis of amyloid deposits in the intramural coronary arteries demonstrated that occlusive arteries were predominant in the surrounding area of myocardial fibrosis, and the extent of coronary stenosis by amyloid deposition was significantly more severe than in hearts of the five control patients who had coronary amyloidosis without myocardial fibrosis. These results indicate that myocardial fibrosis originates from coronary ischemia due to vascular amyloid deposition. This is the first time that the relationship between myocardial lesions and coronary amyloid deposition has been elucidated using histopathologic quantitative analysis.

Castleman's disease of the abdomen and pelvis: report of three cases and a review of the literature.

Three cases of Castleman's disease (CD) of the abdomen and pelvis are reported. Tumoral lesions were located in the lymph nodes of the head of the pancreas, the gastropancreatic fold, and around the left iliac artery. Histologically, all the tumoral lesions demonstrated the hyalinevascular type of CD. This unusual presentation made CD difficult to diagnose preoperatively, since these lesions more closely resembled malignant tumors on computed tomography and angiography. We discuss the problems of diagnosing and classifying CD, together with a review of the literature.

Severe mitochondrial cardiomyopathy and extra-neuromuscular abnormalities in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode (MELAS).

An autopsy case of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) in a 56 yr-old woman is reported. Histopathologic abnormalities are shown widely in the heart, liver, kidney, pancreas and thyroid gland, other than the central nervous system and skeletal muscles that had been so far emphasized in the cases of MELAS. Particularly in the myocardium, focal fibrosis and a disarray of myofibrils were demonstrated, which closely resembled that seen in idiopathic hypertrophic cardiomyopathy. In addition, unique mitochondrial abnormality exhibiting a central glycogen aggregation with surrounding multiple radiating cristae was noted in some cardiomyocytes, which has never been reported in previous cases of MELAS. Thus, in MELAS, various histopathological abnormalities including the mitochondrial abnormalities may involve tissues other than those of the neuromuscular system.

Isolated pulmonary giant cell vasculitis.

An autopsy case of granulomatous vasculitis confined to the pulmonary vasculature in a 40-year-old woman with widespread ovarian carcinoma is reported. Although gross lesions were not identified in the lungs other than a few metastatic tumor nodules, vascular lesions were demonstrated microscopically throughout both lungs. Histopathologically, granulomatous vasculitis was present only in the large and medium-calibered pulmonary arteries of elastic type and in pulmonary veins. Granulomas were distributed mainly in the media and adventitia. The lumina of arteries and veins were free from any occlusion or dilatation. In the granulomas, multinucleated giant cells of both foreign body and Langhans' types containing asteroid body often appeared with slight infiltration by T-lymphocytes. Fibrinoid necrosis was absent in the granulomatous lesions, and neutrophils and eosinophils were also not present. The pulmonary granulomatous vasculitis in this case is distinctly different from the other pulmonary necrotizing and granulomatous vasculitides previously reported.

A case of basaloid-squamous carcinoma of the esophagus: immunohistochemical and ultrastructural studies.

A case of basaloid-squamous carcinoma of the esophagus in an 83 year old man is reported. The esophageal tumor showed a fungating growth at the junction of the middle and lower esophagus and was composed microscopically of submucosal multiple nests with solid and cribriform-like patterns accompanied with a small focus of squamous cell carcinoma adjacent to the overlying esophageal epithelium. The structural features closely resembled those of basaloid-squamous carcinoma. The submucosal tumor cells were immunohistochemically positive for epithelial membrane antigen, wide spectral keratin, alpha actin and S-100 protein. By electron microscopy, the tumor cells had microvilli, desmosomes and bundles of myofilaments, and replicated basement membranes were frequently observed adjacent to the nests. The positive immunoreaction of S-100 protein and alpha actin and the existence of bundles of myofilaments indicated that the present tumor did not correspond well with basaloid-squamous carcinoma. In addition, there was no evidence of true glandular lumina in the tumor nests, a finding which was inconsistent with that of adenoid cystic carcinoma. From the immunoreactivity of S-100 protein and ultrastructural features, it was considered that the present submucosal tumor had originated from undifferentiated pluripotential primitive cells, which differentiated to myoepithelial cells.

Cardiac pseudoaneurysm caused by mitral ring calcification.

A case of left ventricular pseudoaneurysm caused by mitral ring calcification (MRC) in a 71-year-old woman is reported. MRC was initially detected by two-dimensional echocardiography. Two months later, rupture of the posterior wall and pseudoaneurysm formation were diagnosed. Mitral value replacement and reconstructive surgery of the myocardial wall were performed. The patient died 46 days after the operation. At autopsy, there was no histopathological evidence of myocardial infarction, infective endocarditis, or other conditions affecting the cardiac endomyocardium. Pseudoaneurysm apparently resulted from left atrial and ventricular tears caused by MRC.

Multiple penetrating colonic ulcers in secondary amyloidosis caused by rheumatoid arthritis.

An autopsy case of multiple penetrated colonic ulcers with secondary amyloidosis caused by rheumatoid arthritis in a 61 year old woman is reported. Amyloid deposition was conspicuous in the transverse colon with numerous penetrating ulcers that were circumferentially scattered. Deposition was mainly in the small vessel walls of the submucosal layers. In the quantitative comparison of the histological components between the colonic segments affected by severe and mild ulcer formation, occlusive vascular amyloid deposition was revealed more frequently in the severe involved portion than in the mild involved portion. In addition, submucosal fibrosis that tended to appear around ulcers was more extensive and thicker in the former than in the latter. The complete vascular occlusion caused by amyloid deposition was particularly concentrated in the submucosal layer adjacent to the ulcer. These findings indicate that peripheral circulatory disturbance by amyloid deposition in the small vascular walls leads to ulcer formation in the colon.