Detection of nephritogenic antigen from the Lewis rat renal tubular basement membrane

Immunopathogenicity of trypsin-solubilized or non-solubilized renal tubular basement membrane (TBM) of the Lewis (LEW) rat was investigated. Autoimmune tubulointerstitial nephritis (TIN) was induced in BALB/c mice by immunization with trypsin-solubilized LEW rat TBM, while immunization with non-solubilized TBM did not produce the disease. Based on this preliminary experiment we studied the characterization of immunogenic and nephritogenic TBM antigen of the LEW rat. TIN was characterized by severe mononuclear cell infiltrates with multi-nucleated giant cells in the interstitium, tubular destruction and intensive IgG and C3 deposits along the TBM. Anti-TBM antisera and eluate from the nephritic mouse kidneys reacted with the TBM of normal LEW rat kidney by immunofluorescence. LEW rat TBM was also detected immunofluorescently by using antisera from BALB/c mice immunized with autologous trypsin-solubilized TBM. A competitive inhibition test revealed a higher titer of anti-TBM antibody in the eluate than in the adsorption-treated antisera per microgram IgG. Immunoblotting showed one reactive band with a molecular weight of 45,000 daltons, and the blotting patterns in tryptic TBM of the Brown Norway (BN) and LEW rats appeared similar. Amino acid analysis of nephritogenic LEW rat tryptic TBM showed that it contained no hydroxyproline and hydroxylysine, suggesting that this TBM preparation was not collagenous. These findings suggest that tryptic digestion contributes to the release of nephritogenic antigen from the LEW rat TBM and that this antigen system might participate in the immune system involved in the anti-TBM associated TIN that is well known to be induced by non-digested TBM of TBM antigen positive animals.     

A case of double cancer: renal cell carcinoma and transitional cell carcinoma of urinary bladder

This is a case report on a patient with double cancer of kidney and urinary bladder. The patient was a 65-year-old female, and she was admitted with the chief complaint of gross hematuria and right flank pain. After careful examinations, she was diagnosed with right nonfunctioning kidney caused by invasive bladder cancer. Computerized tomography incidentally revealed a mass in the upper pole of the left kidney. Selective left renal arteriography showed stretched arteries and irregularity and tortuosity of the smaller vessels. She was diagnosed with double cancer of bladder and left kidney. Owing to the damage of the right renal function, left partial nephrectomy, total cystectomy, right nephroureterectomy and left ureterocutaneostomy were performed. According to DMSA scintigraphy measured 15 days later, the uptake value of the left kidney was 13.25%, compared to the preoperative value of 25.62%. To date, this case is 36th reported case in Japan.     

Liver damage by the crown-of-thorns starfish (Acanthaster planci) lethal factor

Upon autopsy of mice injected with the crown-of-thorns starfish (Acanthaster planci) lethal factor, a change in color of the liver, swelling of the gall bladder and jaundice were observed. After administration of the lethal factor into mice, activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactate dehydrogenase (LDH), acid phosphatase (ACP) and alkaline phosphatase (ALP) were significantly elevated in serum. Hepatic ALP also increased markedly but hepatic GOT, GPT and ACP showed a tendency to decrease. Activity of hepatic LDH first decreased and then returned to control level. Histopathological studies showed that severe degenerative changes such as enlargement and necrosis of hepatocytes were caused in the mouse liver by the lethal factor. These results strongly suggested that the A. planci lethal factor is a potent hepatotoxin.     

Expression of matrix metalloproteinase matrilysin (mmp-7) was induced by activated ki-ras via ap-1 activation in sw1417 colon cancer cells

The matrix metalloproteinase matrilysin (MMP-7) is a member of the matrix metallo-proteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We have previously found that matrilysin mRNA is specifically expressed in colorectal cancers and adenomas and that its message is localized in the tumor cells themselves. We examined the effects of activated Ki-ras oncogene on the expression of matrilysin in colon cancer cells. We showed that both mRNA and the enzymatic activity of matrilysin were induced by the introduction of activated Ki-ras into SW1417 colon cancer cells. To understand the mechanisms regulating this induction, we analyzed alterations of AP-1 activity induced by activated Ki-ras, using the chloramphenicol acetyltransferase assay. AP-1 activity in SW1417 cells expressing activated Ki-ras was higher than that in control cells. The gel-shift assay also showed higher levels of AP-1 binding protein in SW1417 cells expressing activated Ki-ras than those in control cells. Our results suggest that activated Ki-ras may play a role in inducing expression of matrilysin through an AP-1-dependent pathway in colon cancer cells.     

Accumulation of cyanide and thiocyanate in haemodialysis patients.

BACKGROUND: Cyanide is a toxic agent, and its detoxification product, thiocyanate, may be a major pathogenetic substance in uraemia. Recent studies examining the myeloperoxidase(MPO)/thiocyanate system have suggested a link between thiocyanate and atherosclerosis. However, inaccuracies in conventional assays for cyanide and thiocyanate have limited the understanding of their metabolism in haemodialysis (HD) patients. METHODS: We used high-performance liquid chromatography to measure cyanide in erythrocytes and thiocyanate in plasma in 43 HD patients and in a group of 46 healthy controls that included 15 current smokers. To clarify the metabolic conversion of cyanide to thiocyanate in uraemic patients, we also measured cysteine and sulfate. We then used stepwise regression analysis to analyse factors that determine erythrocyte cyanide and plasma thiocyanate. RESULTS: Mean cyanide and thiocyanate were significantly greater in HD patients than in non-smoking controls. However, cyanide was far below lethal concentrations in dialysis patients. Thiocyanate was six to seven times greater in HD patients than in non-smoking controls, and decreases in thiocyanate following dialysis were only 19.3+/-3.5%. Multiple regression analysis showed a positive correlation between cyanide and thiocyanate in controls, but a negative correlation in HD patients. In patients, an inverse relationship between thiocyanate and BUN was also observed. CONCLUSIONS: The elevation of thiocyanate in patients undergoing dialysis probably is secondary to both limited efficiency of HD and deranged metabolism of cyanide and thiocyanate. Because thiocyanate is a preferred substrate for MPO, it may play a role in uraemic complications including cardiovascular events.     

A case of hypertrophic pachymeningitis, resolved by antimicrobial therapy]

A 65-year-old woman with diabetes mellitus and chronic otitis media developed headache, fever, and hoarseness, all of which did not responded to the oral antibiotics. As stiff neck and lower cranial nerve palsies appeared, bacterial meningitis was suspected. Neurological examination revealed the right hearing disturbance, right recurrent laryngeal nerve palsy, left sternocleidomastoid muscle atrophy and bilateral tongue atrophy. The CSF examination revealed mild pleocytosis and elevated protein, but no bacterial organism was cultured from the CSF. CT scans showed bilateral mastoiditis, and the right mastoid process and a posterior part of the petrous bone were eroded, indicating the exposed bony structures to the posterior fossa. MRI scans demonstrated the thickening of the dura mater of the posterior fossa and the right cerebellar tentorium. This is a rare example of bacterial pachymeningitis of the posterior fossa, the clinical symptoms and MRI findings of which resolved solely by antimicrobial agents without corticosteroid.     

Pericardial effusion following pulmonary resection

Objective Postoperative pericardial effusion commonly occurs after open heart surgery. However, after general thoracotomy such as pulmonary resection, there have been few reports of pericardial effusion. The purpose of this study is to investigate patients with pericardial effusion following pulmonary resection.Methods: Among 2,385 patients with pulmonary resection for lung neoplasm in our institute, eight patients, whose pericardium had never been opened during the operation, developed pericardial effusion. The clinical characteristics of the eight patients were analyzed.Results: Pericardial effusion after pulmonary resection was divided into two subtypes: pericardial effusion in three patients with left thoracotomy occurring within 30 days postoperatively, and pericardial effusion in the remaining five patients with right thoracotomy occurring more than 30 days postoperatively. Pericardiotomy or pericardiocentesis was performed in three symptomatic patients, and the remaining five asymptomatic patients were treated with diuretics. Pericardial effusion disappeared in three of the five patients about 1–3 months after the conservative treatment, while, in the remaining patients, because pericardial effusion had increased gradually, pericardiocentesis was performed.Conclusion: From our experience, the treatment strategy of drainage for early pericardial effusion and diuretics for late pericardial effusion seems to be appropriate. (Jpn J Thorac Cardiovasc Surg 2006; 54:193-198)