Two cases of Weil's disease with acute renal failure in the central Tokyo metropolitan area.

The incidence of leptospirosis, or Weil's disease, in developed countries, particularly in temperate regions, has been dramatically decreasing due to recent improvements in the hygienic environment. In these areas, physicians rarely face this disease and inclusion as a differential diagnosis of acute renal failure seems increasingly uncommon. However, we encountered two cases of severe leptospirosis requiring hemodialysis in central Tokyo. Both cases showed hyperbilirubinemia, thrombocytopenia and mental disturbance in addition to acute renal failure. Severe leptospirosis remains associated with high mortality rates, and early clinical suspicion and laboratory confirmation of the disease are crucial. Detailed history-taking suggested that leptospirosis was caused by transmission from rats in both cases. Rodents inhabit most land areas, implying that the disease can occur all over the world, even in huge metropoles such as Tokyo. These two cases indicate the need for awareness of leptospirosis among physicians working even in urban areas of developed countries.

Large perinephric abscess in a patient on maintenance hemodialysis diagnosed by positron emission tomography combined with computed tomography (PET-CT).

Perinephric abscesses in patients on maintenance hemodialysis (HD) have seldom been reported. The case of a maintenance HD patient with a left perinephric abscess is reported. Although the lesion could not be visualized using other imaging examinations, using FDG and positron emission tomography combined with computed tomography (PET-CT), the patient was diagnosed as having a left perinephric abscess and nephrolithiasis. At the patient's request, the perinephric abscess was treated conservatively with antibiotic therapy alone, and it eventually remitted. This is the first case report of a perinephric abscess diagnosed by FDG PET-CT in a patient on maintenance HD. FDG PET-CT appears to be useful for identifying perinephric abscesses in HD patients, resulting in early diagnosis and appropriate therapy for this severe infection.

Hereditary hemorrhagic telangiectasia in a patient with microscopic polyangiitis.

A 55-year-old Japanese woman with microscopic polyangiitis suffered repeated disturbance of consciousness and gastrointestinal bleeding. These problems were initially attributed to microscopic polyangiitis, but hereditary hemorrhagic telangiectasia was finally identified by further workup. Both microscopic polyangiitis and hereditary hemorrhagic telangiectasia are blood vessel-related diseases inducing similar symptoms. To our knowledge, this is the first observation of microscopic polyangiitis and hereditary hemorrhagic telangiectasia in the same patient. From a literature review of the clinical and pathologic manifestations of these diseases, a positive association may exist between the two diseases.

Fluoranthene induces programmed cell death and alters growth of immature B cell populations in bone marrow cultures.

Many studies have demonstrated that polycyclic aromatic hydrocarbons adversely affect mature mammalian immune systems. However, little is known about the cellular mechanism(s) mediating this immunosuppression or the potential for these ubiquitous environmental chemicals to similarly compromise lymphocyte development (lymphopoiesis). Murine bone marrow cultures were exploited in the present studies to evaluate the potential for fluoranthene, a mutagenic, cocarcinogenic, polycyclic aromatic hydrocarbon, to modulate B cell lymphopoiesis. In this well characterized system, interactions between immature bone marrow-derived precursor B (preB) cells and bone marrow-derived stromal cells closely mimic preB-stromal cell interactions in vivo and resemble interactions between other bone marrow-derived hematopoietic cells and their supporting stroma. Data presented herein indicate that: (i) fluoranthene suppresses B lymphopoiesis within 2 days in bone marrow cultures; (ii) fluoranthene suppresses lymphopoiesis at least in part by direct interactions with preB cells; (iii) fluoranthene lymphotoxicity is mediated by rapid induction of DNA fragmentation characteristic of programmed cell death (apoptosis) and (iv) preB cell populations surviving the initial death signal or preB cell populations exposed to lower doses of fluoranthene (0.5-5 micrograms/ml) exhibit altered growth and survival characteristics. The data suggest several levels at which fluoranthene could compromise B lymphopoiesis.

Mechanisms by which benzo[a]pyrene, an environmental carcinogen, suppresses B cell lymphopoiesis.

The capacity for polycyclic aromatic hydrocarbons (PAH) to suppress immune cell function has been well documented. Nevertheless, mechanisms responsible for PAH immunosuppression and potential effects of PAH on lymphocyte development (lymphopoeisis) remain poorly defined. Murine bone marrow cultures were used in the present studies to determine if and by what mechanism(s) benzo[a]pyrene (B[a]P), a prototypic and highly carcinogenic PAH, suppresses B cell lymphopoiesis. Emphasis was placed on similarities between the processes leading to transformation and immunosuppression and on a possible role for programmed cell death (apoptosis) in B[a]P lymphotoxicity. Data presented herein indicate that: (1) B[a]P suppresses B cell lymphopoiesis in bone marrow cultures at extremely low concentrations (10(-8) M); (2) benzo[e]pyrene, the relatively noncarcinogenic congener of B[a]P, is approximately 1000 times less potent than B[a]P in suppressing B cell lymphopoiesis; (3) bone marrow cells from PAH-resistant DBA/2 mice are less sensitive to B[a]P than cells from C57BL/6 mice; (4) B[a]P induces preB cell apoptosis; and (5) alpha-naphthaflavone, an inhibitor of Ah-receptor dependent, P450 isoenzyme activity, blocks B[a]P-mediated preB cell apoptosis and inhibits B[a]P-dependent suppression of lymphopoiesis. The results support the hypothesis that B[a]P suppression of B cell lymphopoiesis is mediated at least in part by the induction of programmed cell death and that the Ah receptor and/or P450 isoenzymes are involved in this process. The results suggest the potential for PAH to affect development of the B lymphocyte repertoire.

Decreased production and responsiveness of interleukin 2 in lymphocytes of patients with nephrotic syndrome.

Production of and responsiveness to interleukin 2 (IL-2) were evaluated in lymphocytes from 18 patients with nephrotic syndrome. The IL-2 production of T cells, when stimulated with autologous non-T cells separated on a polystyrene resin column, was significantly decreased in patients with minimal-change nephrotic syndrome. No significant difference in the level of IL-2 production was noted between minimal-change nephrotic syndrome patients in the nephrotic stage and those in remission. The IL-2 production was also significantly decreased in lymphocytes from patients with membranous nephropathy. The responsiveness to IL-2 was inconstant among patients with nephrotic syndrome. These results indicate that the immune system of regulating IL-2 production is impaired in patients with nephrotic syndrome.

Association of Sjögren's syndrome with hereditary angioneurotic edema: report of a case.

A case of hereditary angioneurotic edema (HANE) associated with Sjögren's syndrome is presented. One of the members of a pedigree of HANE due to deficiency of C1 inhibitor (C1INH) had a positive titer for anti-SS-A and anti-SS-B antibodies in the serum, complaining of symptom of dry eyes and dry mouth. A lip biopsy revealed lymphocytic infiltration of minor salivary glands. The patient had renal tubular acidosis (RTA). Thus the patient was diagnosed as suffering from Sjögren's syndrome with RTA.

Hyperammonemia in a patient with short bowel syndrome and chronic renal failure.

A patient with short bowel syndrome (SBS) and renal failure developed a disturbance of consciousness with hyperammonemia. Abnormally low concentrations of ornithine, citrulline, and arginine were observed on the plasma aminogram. These results suggested that the activities of amino acid synthetase localized in the small intestinal flora were lost. The small intestine is required for arginine synthesis; thus, infusion limited to the essential amino acids to SBS patients will cause a deficiency of the urea cycle intermediates, ornithine, citrulline, and arginine and may lead to hyperammonemia. In addition, the renal insufficiency may have caused decreased excretion of ammonia. In this patient, supplemental arginine improved the symptoms.

Experimental IgA nephropathy induced by a low-dose environmental mycotoxin, nivalenol.

Based on the hypothesis that IgA nephropathy (IgAN) is triggered by some exogenous antigen(s) which induces dysregulation of the mucosal immune system, we developed an experimental model of orally induced IgAN by an environmental mycotoxin, nivalenol (NIV), which often contaminates agricultural products in Southeast Asia and Japan. In the present study, low doses of oral NIV reproducibly induced significant IgA deposits in the glomerular mesangium and elevated serum IgA levels in mice irrespective of the strain; the degree of immunopathological changes analogous to human IgAN was associated with the dose and duration of NIV treatment. Furthermore, a competitive enzyme-linked immunosorbent assay with an NIV analogue-protein conjugate disclosed that the IgA antibody in the sera from the NIV model mice had a higher affinity to the mycotoxin. Conclusively, these findings suggest that NIV induces some pathological changes in mice which resemble those in human IgAN, and that this mycotoxin is associated with pathogenesis in some types of glomerulonephritis.

Renal lesion of type Ia 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.