Dysregulation of autoimmunity caused by silica exposure and alteration of Fas-mediated apoptosis in T lymphocytes derived from silicosis patients.

Silicosis patients suffer from pulmonary fibrosis caused by silica inhalation, as well as autoimmune diseases known as the adjuvant effects of silica. Caplan syndrome complicated with rheumatoid arthritis (RA) is well known epidemiologically, and the incidence of complicated systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and antineutrophilic cytoplasmic antibody (ANCA)-related nephritis have been reported frequently in silicosis patients. To explore the detailed mechanisms of silica-induced dysregulation of autoimmunity, we had focused on Fas/CD95 and Fas-mediated apoptosis because Fas is one of the most important molecules regarding apoptosis of lymphocytes and its alteration makes some T cells survive longer. Additionally, if the long-survived T cells include the self-recognizing T-cell clones, it is easily thought that autoimmune diseases will appear in this situation. Furthermore, regulatory T cells (Treg) showing CD4+25+ and forkhead box P3 (FoxP3)-positive have been a central player in regulating activation of self- and foreign-antigen recognizing T cells, and it has been reported that activation of Treg causes its higher expression of Fas/CD95. Thus, in this review, we introduce the alteration of Fas and related molecules as found in silicosis and also present the Treg function of the CD4+25+ fraction in peripheral blood mononuclear cells derived from silicosis patients.

Apolipoprotein E2/E5 variants in lipoprotein glomerulopathy recurred in transplanted kidney.

Lipid abnormalities are associated with various disorders ranging from generalized atherosclerosis to renal diseases, including lipoprotein glomerulopathy that is characterized by glomerular lipoprotein thrombi and causes type III hyperlipoproteinemia, proteinuria, and renal failure. This study examines lipoprotein glomerulopathy, which recurred in a transplanted kidney. Molecular biologic analysis of the patient's apolipoprotein (apo) E gene demonstrated E2/E5 type variants. Immunohistochemical analysis of the diseased kidney demonstrated various lipid peroxidation-specific protein adducts, suggesting a potential role of oxidative stress in this disorder. Recurrence in the transplanted kidney suggested a pathogenic role of extraglomerular humoral component(s) resulting from abnormal lipoprotein metabolism, presumably linked to apo E and other genetic or acquired factor(s). Furthermore, the finding that the patient showed pathologic abnormalities in the transplanted kidney with no clinical signs or symptoms of renal disease indicated that lipoprotein glomerular damage progresses early before any clinical manifestations.

A mesangium-predominant gene, megsin, is a new serpin upregulated in IgA nephropathy.

Mesangial cells play an important role in maintaining a structure and function of the glomerulus and in the pathogenesis of glomerular diseases. To identify a specific gene expressed in human mesangial cells, we used a rapid large-scale DNA sequencing and computerized data processing to compare the transcripts in cultured human mesangial cells with various different cells and organs. Using this novel approach, we discovered a new mesangium-predominant gene termed "megsin." We obtained a full-length cDNA clone of megsin, which coded for a novel 380-amino acid protein. Amino acid homology search revealed that megsin belonged to the serpin (serine protease inhibitor) superfamily. The amino acid sequences in the reactive loop site of megsin showed characteristic features of functional serpins. Northern blot and reverse-transcribed PCR analyses of various tissues and cells demonstrated that megsin was predominantly expressed in human mesangial cells. In situ hybridization studies showed the megsin expression in the mesangium of normal glomeruli, while it increased in the expanded mesangium of glomeruli from patients with IgA nephropathy with the degree of mesangial proliferation. Here we report a new human mesangium-predominant gene that may function as an inhibitory serpin in normal and abnormal biological processes of glomerulus.

A case of primary intrahepatic sclerosing cholangitis (PISC) complicated with atypical biliary epithelial proliferation.

A 70-yr-old woman was admitted to our hospital with duodenal ulcer and anemia. The result of liver function test was abnormal and showed persistent elevated alkaline phosphatase levels. Thus, after recovery from duodenal ulcer, endoscopic retrograde cholangiopancreatography (ERCP) was performed; the characteristic "beaded" appearance with band-like strictures and saccular outpouchings affecting the intrahepatic biliary system were found. The diagnosis of primary intrahepatic sclerosing cholangitis (PISC) was made on the basis of the generally accepted diagnostic criteria of primary sclerosing cholangitis (PSC). However, the histological finding from a liver biopsy specimen revealed highly atypical epithelial proliferation of bile ducts. This case of PISC complicated with atypical biliary glandular changes is described, and the distinction between PISC and carcinoma of the bile duct is discussed.

A case of traumatic intramural hematoma of the duodenum effectively treated with ultrasonically guided aspiration drainage and endoscopic balloon catheter dilation.

A 52-year-old man was admitted on February 15, 1990, with hiccups and vomiting. He had been well until 13 days before admission when he stumbled and fell when intoxicated, striking his abdomen. A diagnosis of intramural hematoma was made with computerized tomography and sonography of the abdomen after admission, revealing a mass that was intimately related to the duodenum. Treatment of the intramural duodenal hematoma is controversial. However, this case illustrates the ideal situation where conservative management could be applied with total parenteral nutrition, percutaneous aspiration drainage, and endoscopic balloon catheter dilatation of the narrowed lumen of the duodenum. The patient's subsequent course supports the concept of planned conservative management.

[A case of Akiyami C disease, infected in the area of Yoshino].

A 47-year-old male was admitted because of persistent jaundice. Akiyami C disease was diagnosed by serological tests using the microscopic agglutination tests. The source was considered to be a water contaminated with leptospiras which he had drunk while working at a civil engineering job. The reported cases of Akiyami C disease have recently decreased and this is the 6th case reported in the last 15 years.

[Clinical evaluation of cefmetazole in the dermatologic field].

The therapeutic efficacy and safety of cefmetazole, a cephamycin-derived antibiotic in an injectable form were evaluated in patients with pyogenic infection in the dermatological field. Especially, it was found to be extremely effective for the skin diseases due to staphylococci or streptococci. The results obtained were the following; marked improvement in 18 cases and moderate improvement in 34 cases out of 61 cases, attaining efficacy of 86.7%. Side effects were noted as the rise of GOT and GPT in 3 cases, which were normalized by ceasing its further administration. The MIC of cefmetazole against Staphylococcus aureus isolated out of foci was 0.39-6.25 microgram/ml, while those of CEZ, CXM and ABPC used as the controls exceeded 50 microgram/ml in some cases. It is considered thus, that cefmetazole, is superior to these other antibiotics also in terms of MIC.

Columnar epidermal necrosis. A special form of toxic epidermal reaction?

A bizzare erythematosquamous, partially verrucose, crustly or eroded eruption developed in a 6-year-old boy one week after his first measles vaccination. The eruption regressed completely after a two-year clinical course. Histologically, the epidermis showed unique columnar eosinophilic degeneration. There was a dense, mononuclear cell infiltration in the upper part of the dermis. To our knowledge these clinical and histologic features have not been reported in the literature, although they resemble, in some aspects, Kyrle's disease, Mucha-Haberman's disease, or lichen planus verrucosus. Regarding the pathomechanisms underlying the development of this unique epidermal change, a postulate was made that it represented a special form of toxic epidermal reaction, probably resulting from autoagressive lymphoid cell response to epidermal cells. Furthermore, relationship of measles vaccination to this special response is suggested.