A monoclonal antibody CF703 raised against human fetal lung recognizes a novel onco-fetal mucin.

To obtain murine monoclonal antibodies (MAb), mice were immunized with the extract of a human fetal lung from the first trimester of gestation as initial immunogen followed by booster immunization with a human lung cancer cell line. MAb CF703 which reacted to the booster material was screened and selected. In adults, expression of the antigen defined by MAb CF703, CF703 antigen, was shown immunohistochemically in 78% of gastric carcinomas (14/18), 59% of ovarian adenocarcinomas (10/17), 50% of pancreatic carcinomas (5/10), 17% of lung carcinomas (4/24), 50% of uterine cervical adenocarcinomas (2/4), 20% of endometrial adenocarcinomas (1/5) and 10% of renal cell carcinomas (1/10). Other malignant tumors failed to demonstrate the reactivity. MAb CF703 was weakly reactive with only three adult normal tissues including surface lining of gastric mucosa, Brunner's glandular epithelia of the duodenum and columnar epithelia in the uterine endocervix. In fetal tissues, 5 of 23 tissues including squamous epithelia in lower portion of the;esophagus, surface epithelia of gastric mucosae and goblet cells in the small and large intestine were reactive. The CF703 antigen had a molecular weight over 500 kDa and its epitope was carbohydrate in nature by reason of the resistance to proteinase digestion and sensitivity to periodate oxidation, neuraminidase and alkaline-borohydrite. MAb CF703 recognizes probably a unique epitope in oncodevelopmental mucin glycoprotein. Additionally, this immunization method has the advantage of rapid acquirement of MAbs with restricted, narrow cancer spectrum and is a worthy strategy for generating the new MAbs.

Diffuse mesangial sclerosis associated with Kawasaki disease: an analysis of alpha chains (alpha 1-alpha 6) of human type IV collagen in the renal basement membrane.

A case of diffuse mesangial sclerosis (DMS) associated with Kawasaki disease is reported. A previously healthy Japanese girl, aged 4 months, presented with clinical features of Kawasaki disease. At week 10 of the illness, she developed the nephrotic syndrome, which was refractory to steroid therapy. Renal biopsy demonstrated a diffuse mesangial proliferative glomerulonephritis with microcystic tubular dilatation and, ultrastructurally, marked thinning of the lamina densa in the glomerular basement membrane (GBM) and the tubular basement membrane (TBM) of the proximal tubule. She went into chronic renal failure and died at the age of 11 months. At autopsy, the kidney revealed DMS. Histologically, we found Finnish microcystic disease in its early stages in the biopsy. Using a newly developed monoclonal antibody, we analysed the alpha chains (alpha 1-alpha 6) of type IV collagen in the GBM and TBM. There was no defective constitution of alpha chains on the thin GBM, but the thin TBM of the microcystic proximal tubule showed a weak or discontinuous reactivity for alpha 1 and alpha 2 chains, suggesting faulty formation of the basement membrane. The sclerosing glomeruli of the DMS did not depend on collapse of the GBM, which was positive for alpha 3-alpha 5 chains, but mainly on the proliferation of mesangial matrix, which was positive for alpha 1 and alpha 2 chains.

Epstein-Barr virus genome-positive tubulointerstitial nephritis associated with immune complex-mediated glomerulonephritis in chronic active EB virus infection.

Renal involvement is rare in chronic active Epstein-Barr (EB) virus infection. We report a case of a 7-year-old girl with recurrent EB virus infection. She had fever, lymphadenopathy, hepatosplenomegaly, and persistently high titres of IgG to EB virus capsid antigen (VCA) and IgG to EB early antigen with low titres of IgM to VCA. She showed mild haematuria and proteinuria, but had no symptoms of renal failure. Renal biopsy revealed immune complex-mediated glomerulonephritis, which may have been due to a persistently high titre of antibody against EB virus. In addition, a peculiar form of tubulointerstitial nephritis was found. The morphology was characterized by a papillary infolding of the tubular epithelial cell layer into the tubular lumen. The interstitium was surrounded by the infolded epithelium and contained a large number of B-cell dominant lymphocytes. EBV-encoded RNA 1 (EBER-1) gene was detected in the nuclei of some tubuloepithelial cells by in situ hybridization and may have been associated with the pathogenesis of tubulointerstitial nephritis.

Isolation and characterization of tubular basement membrane antigen common to humans and rats.

Using Brown Norway (BN) rats, we isolated and characterized the tubular basement membrane (TBM) antigens that are immunologically common to humans. The renal basement membrane (RBM) of BN rat, as an antigen source, was solubilized with 8 M urea instead of collagenase followed by extraction with 0.5 M NaCl. On frozen section-immunohistochemistry, the autoantibody obtained from BN rats, which had been immunized with human RBM and showed tubulointerstitial nephritis, bound to the TBM, the basement membrane of the Bowman's capsule, and the brush border of the proximal tubules, but not to the GBM of the normal BN rat kidney. Nephritogenic antigens were isolated by immunoaffinity chromatography using Sepharose-bound purified autoantibody. By Western blot analysis of the eluate, bands with molecular weight of 200 kDa and 180 kDa were positively reacted to anti-FX1A (brush border antigen) antibody and were apparently different from the major bands with molecular weight of 145 kDa and 130 kDa. The bands with molecular weight of 145 and 130 kDa showed major cross reactivity with antibodies to fibronectin and laminin. In contrast with these high molecular weight (HMW) bands, the major 60 kDa band with three minor bands showed no reactivity with any type of antibody tested. These results indicated that the non-enzymatic solubilization of RBM is one of the possible procedures for isolating the HMW form of antigens. These antigens may be epitopically modified pre-existing constitutions of the basement membrane and may play a role in the induction of tubulointerstitial nephritis.

Mitochondrial encephalomyopathies preceded by de-Toni-Debré-Fanconi syndrome or focal segmental glomerulosclerosis.

We report two rare cases of mitochondrial encephalomyopathies which were preceded by renal diseases. One occurred in an 11-year-old girl diagnosed with Kearns-Sayre syndrome, which was preceded by de-Toni-Debré-Fanconi syndrome 8 years previously. The other occurred in a 14-year-old girl diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, who developed focal segmental glomerulosclerosis 3 years prior to confirmation of the diagnosis. Tissue from both patient demonstrated morphological abnormalities of the mitochondria in the distal renal tubular epithelium and leiomyocytes of the small renal artery. The present cases illustrate various clinical and morphologic evidence of renal diseases which may further our understanding of mitochondrial encephalomyopathies.

[An autopsy case of prostatic neuroendocrine cell carcinoma and adenocarcinoma initially found by brain and abdominal wall metastasis].

A 62 year-old man had been suffered from headache and left shoulder pain since March 1997. In November 1997, he visited our hospital complaining of work incapability, slow-moving and somnolence. Multiple nodular lesions were found in his brain and abdominal wall. Biopsy of the abdominal wall mass revealed small cell carcinoma/neuroendocrine cell carcinoma. Radiation therapy on brain and abdominal wall was done and these tumor nodules became decreased. However, recurrence and metastasis occurred later and died at March 1998. The autopsy revealed the origin of these tumors was the prostate. The prostatic tumors revealed neuroendocrine cell carcinoma mainly, combining a portion of adenocarcinoma. Most parts of the metastatic tumors were neuroendocrine cell carcinoma. Only the seventh thoracic vertebral metastasis was bone-sclerosing metastasis of adenocarcinoma.

[A case report of Epstein syndrome].

Epstein's triad which is a syndrome with the combination of macrothrombocytopenia, deafness and nephritis, is similar to Alport's syndrome. We report on a case of Epstein syndrome and describe the results of morphological examination of a renal biopsy, specimen. The patient was a 14-year-old girl with the diagnosis of chronic idiopathic thrombocytopenic purpura that had preseated from the age of 3 years. She was referred to Daisan Hospital of the Jikei University School of Medicine on April 1, 1991 for refractory thrombocytopenia. She had shown sensorineural hearing loss since the age of 6 years and her peripheral blood smear revealed giant platelets on admission. She was treated with interferon, prednisolone, and high-dose gamma-globulin (400 mg/day x 5 days). However, the platelet count did not increase, but hypermenorrhea continued. She subsequently showed proteinuria and hematuria. She underwent splenectomy and renal biopsy on August 12, 1992. The glomeruli appeared to be almost normal under light microscopy. The interstitium showed regional fibrosis containing foam cells and the renal tubuli showed mild atrophy. Under electronmicroscopy, the basement membrane of the glomeruli was associated with mesangial interposition and the lamina densa was split into several layers. These ultrastructural findings were compatible with those of Alport's syndrome.

Usefulness of 31P-MRS as a method of evaluating the viability of preserved and transplanted rat liver.

We used phosphorus-31 magnetic resonance spectroscopy (31P-MRS) to evaluate the viability of transplanted rat liver. Wistar rats were used as donors and recipients. The donor livers were preserved in saline (group 1), Euro-Collins solution (group 2), or in University of Wisconsin (UW) solution (group 3) for 3 and 6 h in groups 1, 2 and 3 and for 9 h in groups 2 and 3. Thereafter the livers were orthotopically transplanted. 31P-MRS spectra were measured after portal reperfusion. Finally, all the recipients were divided into survivors and non-survivors. Survival rates were better in group 3 than in groups 1 and 2. In the 9-h-preserved livers, the livers in group 3 showed a significantly higher beta-ATP/Pi ratio than those in group 2. Comparing survivors and non-survivors in the 6-h-preserved livers in group 2, survivors' livers showed significantly higher beta-ATP/Pi ratio than those of non-survivors. We concluded that 31P-MRS is a useful method for assessing viability of rat liver grafts.

C4d and/or immunoglobulins deposition in peritubular capillaries in perioperative graft biopsies in ABO-incompatible renal transplantation.

We evaluated 0 h and/or 1 h graft biopsy specimens from 14 recipients in ABO-incompatible renal transplantation using immunofluorescence for C4d, IgG, and IgM. All 0 h biopsy specimens revealed negative C4d, IgG, and IgM deposition in peritubular capillaries (PTC). In contrast, 8 of 14 1 h biopsy specimens revealed a positive C4d deposition in PTC. Eight specimens revealed positive IgM staining and seven of them had both C4d and IgM depositions. Three specimens had C4d, IgM, and IgG depositions in PTC. Three of eight patients with C4d deposition and two of six patients without C4d deposition in the 1 h biopsy group suffered from acute rejection within 1 month of transplantation. These findings suggest that complement fragments and immunoglobulin deposition in PTC in ABO-incompatible renal grafts can start soon after reperfusion, although acute rejection may or may not develop.

Nephrotic syndrome associated with diffuse mesangial hypercellularity: is it a heterogeneous disease entity?

Diffuse mesangial hypercellularity (DMH) is a rare primary mesangial proliferative glomerulonephritis associated with idiopathic nephrotic syndrome (INS). We conducted this study on 15 patients, including 5 patients with repeated specimens, with a follow-up of 0.9-17.5 years and evaluated the clinical course and pathological findings. Seven patients were male. Ten patients were under 14 years of age. All specimens had INS and were diagnosed morphologically with primary diffuse mesangial proliferative glomerulonephritis at initial biopsy; 4 were diagnosed with focal segmental glomerulosclerosis (FSGS) within 3 years by the second biopsy. The remaining 11 patients included 8 initial responders and 3 initial nonresponders to 8 weeks' steroid therapy and had the histologic variant of the minimal-change nephrotic syndrome (MCNS). Ten of the 11 patients had normal renal function during the investigation period. One patient with the MCNS variant who was refractory to steroid therapy developed end-stage renal disease (ESRD) within 6 years. Four patient with the histologic variant of FSGS included 1 initial responder, 2 late responders, and 1 steroid-refractory case. One patient with the FSGS variant developed ESRD within 4 years. The follow-up biopsies documented that the severity of mesangial hypercellularity was associated with the severity of proteinuria or hematuria. We conclude that DMH may be divided into heterogeneous disease entities, whereas morphologic changes in initial biopsies were similar. Each variant as well as the degree of DMH should be recognized routinely by follow-up biopsy, because they are prognostic indicators.