Yozo Masugi

EXPERIMENTAL MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS IN RATS INDUCED BY INTRAVENOUS ADMINISTRATION OF ANTI-THYMOCYTE SERUM

Focal glomerulonephritis was induced in rats, by a single intravenous injection of anti‐Thy‐1.1 antibody (ATS). One hour after the administration, the glomeruli of affected rats developed necrotic changes of the mesangial cells while after two hours, mesangiolytic changes appeared. From six days onwards, focal segmental mesangial proliferation which persisted until 30 days, occurred. This is thought to be the first report of experimental nephritis induced by pure anti‐mesangial antibody.

Role of elastic fiber degradation in emphysema-like lesions of pulmonary lymphangiomyomatosis

To study the pulmonary structural remodeling in pulmonary lymphangiomyomatosis, electron microscopy and light and electron microscopic immunohistochemical observations for elastin and alpha 1-antitrypsin were performed on five open lung biopsy samples. Lung specimens showed emphysema-like changes in areas of abnormally accumulated smooth muscle cells. In the alveolar walls having accumulated smooth muscle cells, elastic fibers were decreased in number, disrupted, granular, and occasionally accumulated. Ultrastructurally, elastic fibers in areas of smooth muscle cell accumulation showed poorly outlined amorphous components and a few microfibrils, and occasionally showed electron-dense granular deposits in and around the amorphous components. Spiraling collagen fibrils were frequently found associated with these abnormal elastic fibers. Immunohistochemistry for elastin showed even staining of amorphous components of elastic fibers in the areas of smooth muscle cell accumulation. alpha 1-Antitrypsin was also detected evenly in amorphous components of elastic fibers in the areas of smooth muscle cell accumulation. It is proposed that the emphysema-like lesions of lymphangiomyomatosis are mediated by the degradation of elastic fibers, and these degraded elastic fibers are related to an imbalance of the elastase/alpha 1-antitrypsin system similar to the probable pathogenesis of emphysema.

Histogenesis of unique elastinophilic fibers of elastofibroma: Ultrastructural and immunohistochemical studies

Electron microscopy and both light and electron microscopic immunohistochemical tests for elastin were employed to study the morphogenesis of the unique elastinophilic fibers of an elastofibroma removed from the subscapular region of a 62-year-old woman. Ultrastructurally, as shown by tannic acid stain, elastinophilic fibers of the elastofibroma consisted of central cores and outer zones. The latter were composed of various sizes of vaguely demarcated, irregularly shaped amorphous components and compactly and randomly arranged large amounts of microfibrils. The electron microscopic immunohistochemical results showed that the small-sized amorphous components and microfibrils in the outer zones of the elastinophilic fibers were stained evenly and of granular texture, but the vaguely outlined large amorphous components were not stained. These findings were interpreted as indicating that the amorphous components of the outer zones of elastinophilic fibers were less compact and allowed the penetration of antielastin antibody. The unique elastinophilic fibers of elastofibromas appear not to be formed by the degeneration of the fibers but by abnormal elastogenesis, including an abnormal arrangement of microfibrils.

Pepsinogens I and II in Gastric Cancer: An Immunohistochemical Study Using Monoclonal Antibodies

Monoclonal antibodies were used to examine the immunohistochemical expression of pepsinogens I and II in 31 early and 76 advanced gastric cancers. Of the 107 carcinomas studied, 19 contained pepsinogen II and only 3, found exclusively in pepsinogen II‐positive cases, contained pepsinogen I. Gastric cancer produces pepsinogen II more frequently than pepsinogen I, and production of the latter is significantly associated with the former. Historically, there were 54 intestinal‐type and 53 diffuse‐type cancers. The former produced pepsinogen II more frequently than the latter. In the diffuse type, the four pepsinogen II‐positive cases were found exclusively in females. Although the pepsinogen expression was independent of the macroscopic features in advanced gastric cancer, it was found that the protruded‐type early gastric cancer produced pepsinogen II more frequently than the depressed type. Incidences of pepsinogen positivity were not different between early and advanced gastric cancers or between cancers with or without lymph node metastasis, suggesting that production of pepsinogen is independent of tumor growth.

A case of Takayasu's arteritis associated with membranoproliferative glomerulonephritis and nephrotic syndrome

We describe a 57-year-old Japanese female who had Takayasus arteritis associated with nephrotic syndrome due to membranoproliferative glomerulonephritis. Although a focal and segmental mesangial proliferative glomerulonephritis associated with Takayasus arteritis has been described, membranoproliferative glomerulonephritis has not been reported previously in this condition.

In Situ Localization of Pepsinogens I and II mRNA in Human Gastric Mucosa

Localization of pepsinogens I and II mRNA in the human gastric mucosa was investigated by an in situ hybridization method using digoxigenin labeled cDNA probes. Gastric fundic mucosa from healthy volunteers, which was stained with digoxigenin labeled pepsinogens I and II cDNA probes, showed positive staining in the cytoplasm of both chief cells and mucous neck cells. In contrast, gastric antral mucosa stained with the pepsinogen I cDNA probe showed no positive reaction in the surface mucous cells or pyloric glands. On the other hand, the pyloric glands were stained positively with the pepsinogen II cDNA probe and the staining appeared to be identical to that obtained with the anti pepsinogens I and II monoclonal antibodies using the avidin biotin peroxidase complex technique. These results are consistent with those of previous studies that have employed immunochemical and immunohistochemical techniques. Acta Pathol Jpn 39: 765 771, 1989.

Renal lesions in a strain of spontaneously diabetic WBN/KOB rats

SummaryIn WBN/Kob strain rats, only males spontaneously develop hyperglycemia, glycosuria, hypoinsulinemia and glucose intolerance from about nine months of age. The kidneys of male rats of this strain were histopathologically studies to evaluate the changes which appeared as complications of diabetes mellitus. Thickening of the basement membrane, increase of the mesangial matrix and fibrin-cap lesions were noted in the glomeruli. Armanni-Ebstein degeneration was occasionally found in the tubules. Linear deposition of plasma components such as IgG and albumin in the basement membrane of the glomeruli, tubules and Bowman’s capsule characterized the immunohistological pattern. These findings are similar to the findings in diabetic nephropathy in humans. Since the onset of diabetes mellitus in the strain is slow and symptoms are generally mild, insulin administration is usually not necessary for survival. This strain, therefore, appears to be an important animal model for the study of complications of diabetes in humans.

Membranous glomerulonephritis associated with active liver cirrhosis both involved by HBs antigen

This is a case report of a 35‐year‐old female who showed a relatively short clinical course of severe liver cirrhosis and proteinuria. On light microscopical studies of autopsy material, besides active postnecrotic type liver cirrhosis, typical membranous glomerulonephritis was found. Immunofluorescent study disclosed not only clustered HBsAg (hepatitis type B surface antigen) in occasional hepatic cells but also beaded granular type deposition of HBsAg, IgG, IgM, IgA and complement Gs along renal glomerular basement membrane (GBM). Electron microscopical study disclosed multiple particulated material in occasional inclusion bodies of hepatic cells and in subepithelial and subendothelial dense deposits along the GBM. Enzymatic immunoelectron microscopical study confirmed these particles especially along the GBM being HBsAg themselves. It was concluded that HBsAg‐Ab (antibody) complex was the pathogenetic factor responsible for the glomerular change of this particular case. Although HBsAg and Ab were examined to be negative in serum throughout the patients clinical course, the possibility of the presence of circulating HBsAg‐Ab complex in serum was discussed.

IMMUNE COMPLEX‐MEDIATED GLOMERULONEPHRITIS AND INTERSTITIAL PNEUMONIA SIMULATING GOODPASTURE'S SYNDROME

An autopsy case of what was clinically considered to be Goodpastures syndrome was Investigated. The lung had hemorrhagic interstitial pneumonia, showing granular patterns of IgG and C3 along the alveoli by the immunofluo‐rescent method and electron‐dense subepithelial deposits by electron microscopy. The kidney had crescentic and segmental necrotizing glomerulonephritis associated with membranous nephropathy. Uneven, continuous patterns of immunofluorescent IgG and C3 along the GBM were noted. Electron microscopy showed numerous subepithelial deposits, and immunoelectron microscopy revealed that IgG was not present in the GBM itself but present in the subepithelial deposits. Anti‐GBM antibody activity was not detected in the serum or the kidney eluate. It was suggested that renal and pulmonary lesions occurred through the same mechanism and in association with immune deposits. We propose that there is a disease having immune complex‐mediated renal and pulmonary lesions which clinically resembles the conventional Goodpastures syndrome.

Calcification in Human Osteoblasts Cultured in Medium Conditioned by the Prostatic Cancer Cell Line PC-3 and Prostatic Acid Phosphatase

A medium that had been conditioned by PC-3 cells stimulated the calcification of a human osteoblastic cell line, Tak-10, in a nonmitogenic culture. The calcification of the osteoblasts was stimulated maximally at a 25% concentration of the conditioned medium. Calcification activity was markedly enhanced by the addition of both prostatic acid phosphatase (PAP) and its substrate, alpha-glycerophosphate, to the medium; however, PAP added alone did not enhance this activity. These results suggest that human prostatic carcinoma cells produce a factor that stimulates the calcification of the human osteoblasts. Results have also suggested that PAP is a requisite for osteogenesis provided that its substrates are abundant in the medium.