Viral gene mutation as determinant of low grade malignancy of lesions induced by perinatal retrovirus infection

Of 108 Wistar/Ma rats perinatally injected with Snyder-Theilen feline sarcoma virus, 75 developed tumors within 60 days (group A), and 25 after more than 117 days (group B). Metastases were detected in 59.1% and 11.8% in group A and B respectively. Antibody to v-fes gene product was found to occur before tumor development in group B and after tumor development in group A. v-Ses was found to be down-regulated and extensively mutated in tumors of group B. These results suggest viral gene mutation as a determinant of low grade malignancy of lesions induced.     

Characterization of connectin-like proteins of obliquely striated muscle of a polychaete (Annelida)

Summary In obliquely striated muscle of polychaete, Neanthes sp., three kinds of connectin (titin)-like high molecular weight proteins, 4000 kDa, 1200 kDa and 700 kDa, were detected by SDS gel electrophoresis and immunoblots using antibodies to vertebrate skeletal muscle connectin and antiserum to the protein in question. The 700 kDa protein was isolated and characterized as a sheet-rich filament 170 nm long and 4 nm wide. Using polyclonal antibodies to the 700 kDa protein, the binding of the immunogold to the thick filament was only demonstrated in high ionic strength relaxing solution which solubilized some myosin. This observation suggested that the 700 kDa protein was localized below the layers of myosin in the thick filament and this localization is different from that of twitchin of C. elegans bodywall muscle that is on the surface of thick filament. The 4000 kDa protein was identified as a very thin filament linking the thick filament to the dense body. The very thin filaments were visualized in gelsolin-treated actin filament-free fibres. The 1200 kDa protein was located in the periphery of the dense body. A model of the elastic filament in polychaete bodywall muscle is presented.     

Bone marrow transplantation attenuates murine IgA nephropathy: role of a stem cell disorder

BACKGROUND: The pathogenesis of IgA nephropathy is still obscure. The aim of this study was to investigate whether the fundamental pathogenesis of IgA nephropathy lies in bone marrow stem cells (BMCs). METHODS: We used donors of two different strains for bone marrow transplantation (BMT) into mice with a high content of serum IgA (ddY strain, HIGA mice), a murine model of IgA nephropathy. One group (B6-->HIGA, N = 5) received BMCs of C57BL/6j (B6) mice, and the other (HIGA-->HIGA, N = 8) were reconstituted with BMCs of HIGA mice. RESULTS: Twenty-six weeks after BMT, in B6-->HIGA mice, mesangial deposits of IgA and C3 were statistically milder than those in HIGA-->HIGA mice. Light microscopic observations disclosed that glomerular sclerosis and mesangial matrix expansion in B6-->HIGA mice were decreased compared with those in HIGA-->HIGA mice. These B6-->HIGA mice also excreted less urinary albumin than HIGA-->HIGA mice. Furthermore, serum levels of IgA in B6-->HIGA mice were markedly lower than those in HIGA-->HIGA mice. Size analysis of serum IgA revealed that macromolecular IgA were notably lower in B6-->HIGA mice than in HIGA-->HIGA mice. CONCLUSIONS: Our results suggest that qualitative and quantitative changes of serum IgA are determined at the level of stem cells, and that BMT from normal donors can attenuate glomerular lesions in HIGA mice. This approach may offer a new avenue to study the pathogenesis of IgA nephropathy.     

Reduction of post-ischemic lung reperfusion injury by fibrinolytic activity suppression

BACKGROUND: Although extensive studies on the detailed mechanisms of ischemia-reperfusion injury have been conducted, the implication of the fibrinolytic system has not been known. To determine the role of the fibrinolytic system in ischemia-reperfusion injury, we used tranexamic acid, a synthetic specific plasmin and tissue-type plasminogen activator inhibitor, to suppress fibrinolytic activity in a rabbit lung ischemia-reperfusion model. METHODS: New Zealand White rabbits were randomly divided into two groups: a simple ischemia group and a group injected with tranexamic acid before left hilar occlusion. After 2 hours of warm ischemia, plasma was collected from pulmonary vessels. Fibrin zymography was used to ascertain fibrinolytic activity, and enzyme-linked immunosorbent assay was used to determine soluble thrombomodulin levels as a marker for endothelial cells damage. Changes in left pulmonary function including arterial oxygen tension, peak airway pressure, and pulmonary vascular resistance were recorded during reperfusion after the 2 hours of warm ischemia. RESULTS: Fibrinolytic activity and soluble thrombomodulin levels increased in the vessels of the ischemic lung, indicating endothelial cell injury. The increased fibrinolytic activity and the rise in soluble thrombomodulin were suppressed by the preadministration of tranexamic acid, resulting in remarkably improved pulmonary function during reperfusion. After 2 hours of reperfusion, the wet-to-dry weight ratios and histological studies showed reduced pulmonary edema in the group that had received tranexamic acid. CONCLUSION: These findings suggest that the fibrinolytic system is involved in the onset mechanism of ischemia-reperfusion injury through induced endothelial cell damage and increased vascular permeability.     

Pigmentation on anterior chamber angle in eyes of patients with atopic dermatitis

PURPOSE: To evaluate pigmentation on the anterior chamber angle in patients with atopic dermatitis. METHODS: This study includes 61 patients suffering from atopic dermatitis who visited our hospital between 1991 and 1995. Gonioscopy, cycloscopy, and fundus examinations with a scleral depressor were performed on every patient during the initial visit, and were repeated every 6 months. Pigmentation on the anterior chamber angle was classified according to Scheie. RESULTS: The pigmentation on the anterior chamber angle at the initial visit was evaluated as grade 0 (15 eyes), grade 1 (81 eyes), grade 2 (21 eyes), and grade 3 (5 eyes). Retinal detachment was found in 9 eyes of the 26 eyes with grade 2 or 3 pigmentation, but in only one of the 96 eyes with grade 0 or 1. The pigmentation on the anterior chamber angle correlated significantly with the incidence of retinal detachment (P < .0001). Causative breaks were found in the peripheral retina or ciliary epithelium in all eyes. CONCLUSIONS: Moderate to dense pigmentation on the anterior chamber angle in patients with atopic dermatitis seems to be a sign of breaks in the retina or ciliary epithelium, and the fundus of these patients should be examined carefully for signs of retinal detachment.     

A case of reflux nephropathy associated with pheochromocytoma]

A 26-year-old female patient complicated with reflux nephropathy and pheochromocytoma is reported. We could not find either intrinsic or extrinsic factor of urinary tract obstruction. The open bilateral renal biopsy was performed at the time of resection of the tumor. The renal biopsy specimen demonstrated minor glomerular change, severe tubular "thyroid-like" appearance and cast formation in the obvious reflux side. Otherwise focal glomerular sclerosis (FGS) lesion was found in less reflux side. In reflux nephropathy, FGS lesion is reported as main cause of progression, but mechanism of FGS lesion is unknown. This case which has both vesicoureteral reflux the high plasma nor-epinephrine concentration was considered to be important to emphasize circulative factor in the pathogenesis of FGS like lesion.     

Role of platelet-activating factor in functional alterations induced by xenoreactive antibodies in porcine endothelial cells

BACKGROUND: Platelet-activating factor (PAF) is a phospholipid mediator of inflammation which has been implicated in rejection. The interaction of anti-alpha-galactosyl natural antibodies (anti-alpha gal Abs) with endothelial cells is the initial step for the development of xenograft rejection. In our study, we stimulated porcine aortic endothelial cells (PAEC) with anti-alpha gal IgG to investigate the synthesis of PAF from PAEC and its biological consequences. METHODS AND RESULTS: PAF was extracted and chromatographically purified from cultured PAEC stimulated with baboon anti-alpha gal Abs. The Abs induced a dose-dependent synthesis of PAF peaking after 30 min of incubation, and decreasing thereafter. Concomitant cell shape change, motility, and cytoskeleton redistribution were observed. These events were prevented by addition of a panel of PAF-receptor antagonists. An SV40 T-large antigen-immortalized PAEC line was engineered to express PAF acetyl-hydrolase (PAF-AH) cDNA, the major PAF-inactivating enzyme. These transfected cells exposed to anti-alpha gal Abs showed reduced cell contraction and motility compared with empty vector-transfected cells. Moreover, in PAEC stimulated with anti-alpha gal Abs, the synthesis of PAF promoted the adhesion of a monocytic cell line as shown by the inhibitory effect of PAF-receptor antagonists and of PAF-AH expression. Finally, studies on cell monolayer demonstrated an enhanced permeability 48 hr after exposure to anti-alpha gal Abs, and this increase was prevented by PAF-inactivation and by PAF-receptor blockade. CONCLUSIONS: These results demonstrate that on stimulation with anti-alpha gal Abs, PAEC synthetize PAF which can contribute to several vascular events involved in xenograft rejection.