Yuzo Endo

Drug-induced generalized phospholipidosis.

Drug‐Induced generalized phosphollpldosis in human beings is described. Detailed study of phospholipid fatty liver, which was first reported by us in 1968, disclosed that phospholipid accumulation is not only found in the liver but is also distributed throughout the body. From clinical as well as experimental survey, it may be concluded that this phospholipido‐sls was caused by administration of 4.4′‐diethylamlnoethoxy hexestrol. Three autopsy cases showed liver cirrhosis of a peculiar form, such as fine granular thln‐septal cirrhosis with phospholipid deposition and alcoholic hyalines. This septal cirrhosis may have resulted from phospholipid deposition. The relationship between alcoholic hyaline and lipid metabolism is discussed. ACTA PATH. JAP. 22: 517–531, 1972.

B-cell lymphoma of mucosa-associated lymphoid tissue of the thymus: A report of two cases with a background of sjogren's syndrome and monoclonal gammopathy☆

Two rare cases of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising in the thymus are reported. Both patients (a 61-year-old man and a 75-year-old woman) were suffering from Sjögrens syndrome and immunoglobulin (Ig)A kappa monoclonal gammopathy. Mixed IgA-IgG cryoglobulinemia was also present in the male case. Tumor cells expressed IgA and kappa antibody reactive proteins identical with serum IgA kappa M. Moreover, we could demonstrate rearrangements of the immunoglobulin heavy and light chain genes, which supported the monoclonal origin of tumor cells. Immunological abnormalities improved after thymectomy in one case in which the tumor cells were confined to the thymus, but not the other with regional lymph node involvement, suggesting a causal role for the tumor. MALT lymphomas of the thymus thus appear to be associated with immunological disorders such as Sjögrens syndrome or monoclonal gammopathy.

Experimental Immunoglobulin A Nephropathy Induced by Gram-Negative Bacteria

A study was conducted to determine whether intraperitoneal and oral administration of formalin-fixed gram-negative bacteria induced immunohistologically and ultrastructurally evident glomerular deposition of IgA and C3 in C3H/HeN mice. Separate treatments with strains of Pseudomonas aeruginosa, Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, and two kinds of lipopolysaccharide (LPS) were used. Two mice in each treatment group were sacrificed at 10, 20 and 30 weeks of age to examine sequential glomerular changes. In addition to the intraperitoneal administration (IP) groups receiving whole formalin-fixed bacterial cells, cell precipitate and supernatant fractions of each bacterial strain after sonication were injected intraperitoneally once a week, and the mice were sacrificed at 30 weeks of age. Sequential quantitation or IgG, IgA or IgM in serum and the isotypes specific for each of the bacterial strains or LPS administered was performed by ELISA. The incidence of immunofluorescence positivity for glomerular IgA and C3 was 37-71 and 37-66.7%, respectively, in the IP groups that had received bacterial cells of each strain, which was significantly higher than that in the IP groups given LPS or in the controls. These results suggest that cell wall components common among gram-negative bacteria, other than LPS, play a major role in the glomerular deposition of IgA and C3. This is the first use of gram-negative bacteria to establish an active model of IgA nephropathy.

Hepatic squamous cell carcinoma with hypercalcemia in liver cirrhosis.

Primary squamous cell carcinoma of the liver is exceedingly rare and has previously been reported in association with hepatic teratoma, hepatic cyst or hepatolithiasis. This paper describes an autopsy case of squamous cell carcinoma which developed with hypercalcemia in a cirrhotic liver. This cancer was characterized histologically, immunohistologically and ultrastructurally, and was found to exhibit immunofluorescence positivity for anti‐epidermal keratin monoclonal antibody, together with the presence of tonofllaments scattered sparsely in the cytoplasm of the cancer cells.

Etiology of IgA nephropathy syndrome

Since Bergers original paper on mesangial IgA‐IgG deposition with hematuria, there have been a number of clinical and pathological studies regarding IgA immune complexes, the mechanisms of glomerular IgA deposition leading to glomerular injury and animal models of IgA nephropathy. During the last quarter of this century, glomerular changes such as IgA nephropathy have also been observed in cases associated with other diseases, such as systemic lupus erythematosus, Schoenlein‐Henoch purpura, liver cirrhosis and chronic inflammatory diseases of the lung. This evidence supports the idea of an IgA nephropathy syndrome. On the other hand, IgA is thought to be an important humoral factor at the mucosal immune system and appears to have an antibody function against various etiologic candidates of extrinsic or intrinsic substances at the mucosal and systemic immune system. Glomerular IgA deposition in IgA nephropathy syndrome is thought to result from elevated levels of circulating immune complexes or aggregated IgA due to an overproduction of polymeric IgA as antibodies in the serum and due to the clearance impairment of IgA immune complexes in the hepatic and splenic phagocytic system. The glomerular IgA subclass is not one‐sided, but should be evaluated in comparison with the age of patients at renal biopsy; this indicates the approximate age of onset. Cirrhotic IgA glomerulonephritis is not related to Hepatitis B or C virus infection, but to the pathophysiologic condition of liver cirrhosis. Various etiologic candidates such as viral, microbial, dietary antigens or auto‐antigens have been listed and experimental models of IgA nephropathy syndrome have provided some clues in understanding the etiology of primary IgA nephropathy. However much still remains to be clarified and some specific epitopes common among these etiologic candidates will have to be identified.

A PROLACTIN PRODUCING TUMOR ORIGINATED IN THE SPHENOID SINUS

The case presented is a prolactin producing tumor originated in the sphenoid sinus of a 40‐year‐old woman. Histologically this tumor is a typical chromophobe adenoma of the pituitary gland. Human prolactin was immunohistochemically detected in the cytoplasm of most tumor cells. The tumor invaded around the pituitary gland and in the nasal cavity without distant metastasis. Clinically the patient showed hyperprolactinemia and amenorrhea.

A case of lymphocytic infundibuloneurohypophysitis: histophathological studies.

A 57-year-old woman presented with 2-year history of polyuria and polydipsia. Hormonal studies revealed almost normal anterior pituitary function and central diabetes insipidus. Magnetic resonance imaging showed thickening of the pituitary stalk and enlargement of the neurohypophysis without high intensity of the posterior lobe on T1-weighted images, which were compatible with lymphocytic infundibuloneurohypophysitis. Transsphenoidal biopsy was done and histological examination disclosed moderate fibrosis and lymphocytic infiltration not only in the posterior pituitary, but also in the adjacent anterior part of the gland. The lymphocytes both in the anterior and posterior pituitary were mainly T cells that were positive for UCHL 1, CD 3, and CD 8. Immunofluorescence of frozen tissue detected immunecomplex deposition in small vessels and the interstitium. These findings suggested that allergic reactions may play an important role in the pathogenesis of lymphocytic infundibuloneurohypophysitis.

Renal Lesion of Type la Glycogen Storage Disease: The Glomerular Size and Renal Localization of Apolipoprotein

In order to investigate the glomerular size and renal localization of apolipoprotein in type Ia glycogen storage disease, a renal biopsy was performed in two proteinuric patients. Histopathological examination of the biopsy specimens revealed focal sclerotic glomerular sclerosis in both patients. The mean glomerular area was 21.6 +/- 11.6 x 10(3) microns 2, indicating enlargement of the glomeruli. Immunohistochemical staining of the specimens for apolipoprotein showed localization of apolipoprotein AI on the inner side of the glomerular capillary wall, and in proximal tubular epithelial cells. In one patient with a history of several episodes of hypoglycemia, treatment with corn starch improved the carbohydrate and lipid metabolic profile and reduced the daily urinary protein excretion from 2.23 to 0.5 g. These results suggest that focal sclerotic glomerular lesions associated with type Ia glycogen storage disease may be related to disorders of carbohydrate and lipid metabolism.

The juxtaglomerular apparatus in IgA nephropathy: An analysis of the transport and fate of IgA deposits at the glomerular hilus

This study on 27 cases of IgA nephropathy has shown that IgA deposits are rare in the juxtaglomerular apparatus (JGA) despite large amounts of IgA deposits in the mesangium. Phagocytes are absent in JGA. A small number of ill-defined, IgA-positive substances are seen in the matrix of lacis cells, and their electron-density is decreased. These findings indicate dissolution of IgA deposits in the intercellular matrix. In addition, it is suggested that the transport of IgA deposits through the glomerular stalk toward JGA is prevented at the border area between the mesangium of glomerular hilus and the lacis cell region. The block is not complete, because small, IgA-positive substances are seen sparsely in the matrix of lacis cells. The structure of the lacis cell region is thought to restrict the passage of macromolecules such as IgA deposits. Frequently positive staining for C3 in the mesangium and lacis cell region and within the wall of afferent and efferent arterioles indicates that C3 is easily accessible to the arteriolar wall adjacent to JGA, by the route through the glomerular stalk and JGA. This may be concerned in the pathogenesis of arteriolar hyalinosis at the glomerular hilus.

A Study of Human Interstitial Lung Diseases with Special Reference to Immune Complexes and Hyaline Membrane

To evaluate the pathogenetic roles of immune complexes and alveolar hyaline membrane in idiopathic interstitial pneumonia (IIP), immunohistological and ultrastructural studies of the kidney and lung were performed in 23 cases of IIP, 19 cases of autoimmune diseases, 17 cases of interstitial pneumonia other than IIP, and 11 cases of bronchopneumonia as a control group. None of the cases of IIP or interstitial pneumonia other than IIP showed immune complexes in the alveolar and glomerular capillary walls. On the other hand, one case of SLE was positive for IgG and components of complement along the alveolar and glomerular capillary walls. The alveolar hyaline membrane in the present cases revealed immunoglobulins as well as components of complement, which were poorly soluble in chaotropic solution or acidic buffer. These results indicate that circulating immune complexes play a minor role in the pathogenesis of IIP and other types of interstitial pneumonia, and that there is no relationship between immune complex deposition in alveoli and the alveolar hyaline membrane. It is necessary to further investigate factors other than immune complexes involved in alveolar tissue damage and to clarify the significance of the hyaline membrane in the processes occurring from acute changes to pulmonary fibrosis in IIP.