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Biomedical subjects

B Akikusa

Publications and source records attributed to B Akikusa.

At least 19 recordsLinked to original sources
PubMed1999

Mast cells induce autoantibody-mediated vasculitis syndrome through tumor necrosis factor production upon triggering Fcgamma receptors.

The generation of autoantibodies and deposition of immune complexes (ICs) in tissue play a primary role in autoimmune diseases. However, the IC-triggered response consists of complex mechanisms that make it difficult to identify the pathogenesis and develop specific therapy. We clarified here a sequential mechanism for the induction of hypersensitivity angiitis by analyzing the responsible Fc receptor (FcR), effector cells, and mediators in an animal model using FcR-deficient mice. In this model, rheumatoid factor-mediated skin vasculitis was induced in wild-type mice, whereas FcRgamma-deficient mice did not develop the vasculitis. Adoptive transfer of various FcR(+) cells into FcRgamma-deficient mice showed that mast cells but not macrophages derived from wild-type mice triggered skin vasculitis. Mast cells derived from either FcgammaRIII-deficient or tumor necrosis factor (TNF)-deficient mice did not possess the inducibility of skin vasculitis. These results indicate that triggering of vascular inflammation was induced by mast cells through IC binding on FcgammaRIII. TNF produced by such activated mast cells was mainly responsible for the pathogenesis of autoantibody-mediated vasculitis. These findings illustrate the clinical significance of mast cells, Fcgamma receptors, and TNF in IC-induced vasculitis syndrome.

Animals↗
PubMed1999

Effect of pituitary microsurgery on acromegaly complicated nephrotic syndrome with focal segmental glomerulosclerosis: report of a rare clinical case.

A case of nephrotic syndrome complicated by acromegaly is presented. The first renal biopsy specimen showed minor glomerular abnormalities with glomerular hypertrophy, corresponding with minimal change nephrotic syndrome. Corticosteroid therapy led to a partial remission, followed by frequent relapses after reduction of the drug. A diagnosis of atypical focal segmental glomerulosclerosis (FSGS) was made based on the second renal biopsy results 6 months after the first. We combined steroid therapy with the administration of an anticoagulant, cytotoxic agents, angiotensin-converting enzyme inhibitor, and low-density lipoprotein adsorption. Except for the angiotensin-converting enzyme inhibitor, these medications were not effective in terms of allowing a reduction in the high dosage of steroid, which in turn threatened progressive osteoporosis and lumbar vertebrae fracture. Administering the steroid at a moderate dosage, treatment was focused on the complicating acromegaly from pituitary microadenoma. Subcutaneous injections of octreotide acetate, a somatostatin analogue, reduced proteinuria and increased urine volume. Subsequent transsphenoidal microsurgery of the adenoma resulted in the normalization of the elevated creatinine clearance and the further reduction in steroid dosage while maintaining a remission state. This is the first reported clinical case with acromegaly followed by FSGS, and it is suggested that hypersecretion of growth hormone participates in the development and progression of glomerular disease.

Acromegaly↗
PubMed1998

Demonstration of microaneurysms at the interlobular arteries of the kidneys in microscopic polyangiitis: a three-dimensional study.

Aneurysms, mostly saccular, of the medium-sized muscular arteries are frequently encountered in classic polyarteritis nodosa, whereas their occurrence in smaller arteries is unclear. The objective of this study is to clarify the three-dimensional morphology of the small-sized muscular arteries involved in microscopic polyangiitis (MPA). Six autopsy cases of MPA of the acute inflammatory stage were chosen. Using serial paraffin-embedded sections of the kidney, vasculitic lesions observed in the interlobular arteries were three-dimensionally reconstructed. All of the 19 lesions showed microaneurysms, of which 18 were sausage-shaped and the other was saccular. In the former type, average outer diameter at the most expanded point was 235.4 +/- 83.8 microm (mean +/- SD), which was 2.78 +/- 0.73 times that of an uninvolved adjacent arterial diameter. The major axis-minor axis ratio in a cross-aneurysmal section was 1.17 +/- 0.16, indicating rather regular centrifugal expansion of the aneurysm. The aneurysmal length was 742.7 +/- 254.8 microm. These sausage-type aneurysms showed whole circumferential vasculitic involvement, whereas the saccular-type aneurysm contained an uninvolved arterial portion. In both types, the luminal spaces showed similar three-dimensional features to the outer surface of microaneurysms It was concluded that the interlobular arteries of the kidneys in MPA were characterized by formation of microaneurysms, most of which were sausage-shaped

Actins↗
PubMed1998

Routes of hepatic metastasis of gallbladder carcinoma.

This clinicopathologic study aims to clarify routes of hepatic metastasis of gallbladder carcinoma. Nineteen liver specimens obtained by extensive hepatectomy performed for the treatment of advanced gallbladder carcinoma were analyzed. We defined hepatic metastasis as a discrete hepatic lesion separate from the primary tumor and paid special attention to portal tracts at the margins of direct hepatic invasion. Eleven early metastatic foci were demonstrated histologically in 6 cases, most commonly in segments adjacent to the gallbladder. All cases with hepatic metastasis had direct hepatic invasion. Nine of the 11 metastatic lesions were located within the portal tracts or accompanied by invasion into the portal tracts. Because they are in continuity with areas of direct hepatic invasion, the portal tracts at the invasive margin often were involved by cancer cells that spread along these tracts. These results suggest that the most important route in development of hepatic metastasis from gallbladder carcinoma is along the portal tracts after direct hepatic invasion.

Aged↗
PubMed1997

Increased blood plasminogen activator inhibitor-1 and intercellular adhesion molecule-1 as possible risk factors of atherosclerosis in Werner syndrome.

Werner syndrome is a rare premature aging syndrome accompanied by severe atherosclerosis. The etiology of atherosclerosis is suspected to be due to its complications, namely diabetes mellitus, hyperinsulinemia and hyperlipidemia. But from an autopsy case we found that some other risk factors may be involved in the mechanism of atherosclerosis in this syndrome. Previously we revealed that the plasminogen activator inhibitor-1 (PAI-1) gene was being overexpressed in skin fibroblasts from a patient with this syndrome. PAI-1 is a potent inhibitor of tissue plasminogen activator and a possible risk factor of atherosclerosis. This led us to assess the plasma concentration of PAI-1. Our working hypothesis was that the PAI-1 gene was upregulated or not fully suppressed in cells responsible for the production of PAI-1 in plasma as well as in fibroblasts. The results show a high concentration of plasma PAI-1. One of the well-known physiological substances that induce the PAI-1 gene is tumor necrosis factor-alpha, which also induces other possible risk factors of atherosclerosis, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1. We found the serum concentrations of ICAM-1 to be elevated in patients with this syndrome. We conclude that high concentrations of PAI-1 and ICAM-1 in blood may be one of the potent causes of severe atherosclerosis in Werner syndrome.

Adult↗
PubMed1997

Necrotizing alveolar capillaritis in autopsy cases of microscopic polyangiitis. Incidence, histopathogenesis, and relationship with systemic vasculitis.

OBJECTIVES: To determine the incidence of necrotizing alveolar capillaritis, to elucidate its histopathogenesis and the most reliable histopathologic features for its detection, and to explore its relationship with systemic vasculitis in microscopic polyangiitis. METHODS: Twenty-five autopsy cases of microscopic polyangiitis were examined. Double staining with periodic acid-silver methenamine and trichrome was used. RESULTS: Periodic acid-silver methenamine and trichrome staining proved to be a useful and convenient method for the detection of necrotizing alveolar capillaritis. Capillaritis was detected in 10 (40%) of the 25 cases studied. Of 18 cases that exhibited the early degenerative stage of systemic vasculitis, capillaritis was seen in 10 (56%). Fibrinoid necrosis of the alveolar wall was the most reliable histopathologic feature for detecting necrotizing alveolar capillaritis in microscopic polyangiitis. The early stage of capillaritis displayed very little neutrophil exudation, and conspicuous accumulation of neutrophils developed after fibrinoid necrosis. Statistical analysis revealed that alveolar capillaritis had a statistically significant correlation (P < .05) with necrotizing vasculitis of the pulmonary circulatory system. Capillaritis tended to occur when systemic vasculitis of microscopic polyangiitis was in its early degenerative stage. CONCLUSION: Necrotizing alveolar capillaritis was detected in about half of the microscopic polyangiitis autopsy cases that exhibited the early degenerative stage of systemic vasculitis, and results based on earlier reports of clinical observations may have been too conservative.

Adult↗
PubMed1997

[Focal segmental glomerulosclerosis presenting nephrotic syndrome and acute renal failure in a patient with rheumatoid arthritis].

A 45-year-old woman with rheumatoid arthritis(RA) who developed nephrotic syndrome and acute renal failure was reported. She first noticed polyarthritis in June 1990, and was diagnosed as RA. Since her RA was not controlled with nonsteroidal anti-inflammatory drugs (NSAID), she started taking prednisolone 10 mg daily and received 100 mg of D-penicillamine from October 1990 with improvement of the RA. In March 1991, she noticed edema of the face and legs, at which time massive proteinuria and hematuria were first noted. Because of her nephrosis, she was referred to our hospital for further evaluation. Laboratory investigations revealed 24-hour urine proteinuria of 37 g, serum creatinine, 2.7 mg/dl, blood urea nitrogen, 43.5 mg/dl, total protein, 4.1 g/dl, albumin, 1.5 mg/dl, and total cholesterol, 600 mg/dl. The rheumatoid factor and anti-nuclear antibody were positive. Renal biopsy showed focal segmental glomerulosclerosis (FSGS). Her nephrotic syndrome and renal dysfunction recovered after the administration of prednisolone at 60 mg/day. The possible pathogenesis of FSGS in patients with RA was discussed.

Acute Kidney Injury↗
PubMed1996

[Study on a predictive marker for evaluating the effectiveness of steroid therapy in IgA nephropathy-significance of extracapillary changes].

In order to obtain a useful index that can predict the effectiveness of steroid therapy in IgA nephropathy, we investigated the relationship between steroid therapy and extracapillary change. We analysed 51 cases consisting of a group of 24 cases in which steroid was administered (initial dose: prednisolone 20-60 mg/day orally, or pulse therapy), and a group of 27 cases in which steroid was not administered. First of all, we compared these two groups in terms of a clinical improvement rate over 3, 12 and 60-month-periods after the therapy, respectively. It was found that steroid therapy led to a higher improvement rate (p < 0.01-0.05), indicating that steroid is effective for IgA nephropathy. Among the group undergoing steroid therapy, the frequency of cellular crescents (C) was significantly higher (p < 0.05-0.01) in the cases in whom steroid was effective and that of fibrous crescents or adhesion (F) was significantly lower (p < 0.05-0.01). We then assessed C/F in each case of the steroid-administered group, and studied its relationship with the improvement rate. As a result, the improvement rate was below 50% in the group of C/F < 0.25, over 50% of the group of 0.25 < or = C/F < 0.75, and 100% of the group of 0.75 < or = C/F. Accordingly, we concluded that C/F could be used a parameter for predicting the effectiveness of steroid therapy in IgA nephropathy and for determining indications for steroid therapy.

Adolescent↗
PubMed1996

[Diffuse proliferative lupus nephritis in a patient with ulcerative colitis].

A 31 year-old man treated with sulfasalazine for ulcerative colitis, developed nephrotic syndrome, photosensitivity, alopecia, lymphopenia and hypocomplementemia. Anti-nuclear antibody (speckled) and antibodies to single-stranded DNA and SS-A were positive, while those against native DNA and histon were negative. Renal biopsy revealed diffuse proliferative lupus nephritis. His nephrotic syndrome partially improved with corticosteroid therapy combined with cessation of sulfasalazine. His complement level became normal, however it decreased again during the gradual reduction of corticosteroid dosage. In conclusion, we diagnosed the patient's illness as an idiopathic syntemic lupus erythematosus rather than sulfasalazine-induced lupus.

Adult↗
PubMed1995

Six cases of microscopic polyarteritis exhibiting acute interstitial pneumonia.

Out of 21 autopsy cases of microscopic polyarteritis (MPA), six cases that died of acute respiratory failure are described. All of these six cases exhibited pauci-immune necrotizing glomerulonephritis. Of these six cases, systemic vasculitis and respiratory failure occurred almost simultaneously in two, whereas respiratory failure developed when vasculitis recurred in the other four. Pathologically, pulmonary changes were diffuse and almost uniform in each case. Interstitial inflammatory cells (alveolitis), hyaline membrane, restructuring, and fibrosis were observed. The degrees of these changes differed from case to case; four cases showed predominantly exudative changes and two cases exhibited proliferative or organizing ones. Clinical and pathological features were consistent with acute interstitial pneumonia (AIP). Immunofluorescent and ultrastructural studies did not suggest deposition of immune complexes at the lesions of alveolitis. An etiologic agent could not be identified in these cases. Some lung lesions including pulmonary hemorrhage have been described in association with MPA; however, cases such as those presented here have rarely been reported. It was considered that AIP could be one of the pulmonary disorders in MPA. Furthermore, the possible pathogenetic role of antineutrophil cytoplasmic antibodies (ANCA) in the evolution of present lung lesion is discussed. Although ANCA were not examined in the present cases, these antibodies should be investigated in future cases.

Acute Disease↗
PubMed1995

In vivo effect of TGF- beta 1. Enhanced intimal thickening by administration of TGF- beta 1 in rabbit arteries injured with a balloon catheter.

The in vivo effect of transforming growth factor-beta 1 (TGF-beta 1) was studied in a model system in which arterial intimal thickening was induced by injury of rabbit arteries with a balloon catheter (BCI). Intimal area and its ratio to medial area in carotid arteries after BCI were significantly higher in rabbits treated with 10 micrograms/kg TGF-beta 1 and 10 mg/kg aspirin i.v. QD (TGF-beta 1 group) than in those treated with 10 mg/kg aspirin i.v. QD only (control group). Intimal cell numbers in the TGF-beta 1 and control groups were not significantly different from each other, but matrix volume in the intimal layer was significantly higher in the TGF-beta 1 group. By immunohistochemical and Northern blot analyses, the fibronectin content in carotid intimal and medial layers was greater in the TGF-beta 1 group compared with that in the control group. Thus, in intimal thickenings induced by BCI. TGF-beta 1 mainly enhanced the formation of matrix containing fibronectin. Moreover, the mRNAs of TGF-beta 1 and type II receptors were detected in carotid arteries 7 and 14 days after, but not before, BCI. Thus, TGF-beta 1 influences the process of intimal thickening induced by BCI through a receptor-mediated mechanism in vivo. The significance of this fact is discussed in relation to the development of atherosclerosis.

Animals↗
PubMed1992

Vasculitis and pyrexia associated with superficial spreading gastric carcinoma.

A case of low-grade fever developing about a month before the discovery of gastric carcinoma is reported. No findings of infection or collagen disease were revealed. The fever continued for about 3 months, but promptly disappeared after surgical removal of the tumor. A superficial spreading mucosal carcinoma with minimal invasion to the submucosa was seen in the antrum, showing the features of poorly differentiated adenocarcinoma. In addition, unique venous inflammation was recognized beneath and around the neoplasm. Arteries and lymph vessels did not exhibit any inflammatory changes. It was presumed that the gastric carcinoma had induced phlebitis, which subsequently brought about the fever. As to the pathogenetic mechanism, it was suggested that a substance produced by the carcinoma cells flowed into nearby veins to induce the phlebitis.

Adenocarcinoma↗
PubMed1992

[Intrarenal arterial Doppler sonography in patients with various renal disease: correlation of resistive index with biopsy findings].

Duplex Doppler sonography (ultrasonic equipment: Toshiba SSA-270A) were performed in the patients with various renal disease (male 44, female 32) admitted to our hospital between June 1990 and August 1991. Interlobar arterial blood flow velocity was measured at the side of renal pyramid through a longitudinal scan. Both the maximum blood flow velocity (Vmax) and the minimum blood flow velocity (Vmin) were measured quantitatively and resistive index (RI: defined as (Vmax-Vmin)/Vmax) were calculated. Vmax and Vmin correlated well with the creatinine clearance (Ccr) (r = 0.56, r = 0.66 respectively), whereas RI, by which we can detect Doppler waveform changes, correlated weak with Ccr (r = 0.39). We found twenty-nine patients (40%) with an elevated RI (greater than or equal to 0.70). They had severe renal dysfunction and active pathologic findings in the tubulo-interstitial or vascular compartment of the kidney. Doppler examination of renal blood flow velocity was valuable not only to estimate renal function but also to assess pathophysiology of renal disease.

Adult↗