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Biomedical subjects

Y Fujigaki

Publications and source records attributed to Y Fujigaki.

At least 37 records · Page 2Linked to original sources
PubMed2000

Atypical Fabry's disease presenting with cholesterol crystal embolization.

We describe a 65-year-old man who presented with pulmonary hemorrhage and progressive renal insufficiency three months after resection surgery for an abdominal aortic aneurysm. Intensive treatment with corticosteroids and hemodialysis were not effective, and the patient died. Postmortem examination of the kidneys revealed widespread cholesterol clefts within the renal arterioles and a number of lamellar inclusion bodies were observed by electron microscopy. The diagnosis of Fabry's disease was made by the absence of plasma alpha-galactosidase A activity. This was a very rare case of subclinical Fabry's disease coexistent with cholesterol crystal embolization, mimicking pulmonary-renal syndrome.

Aged↗
PubMed1999

Attenuation of cisplatin-induced acute renal failure is associated with less apoptotic cell death.

To clarify the pathophysiologic role of apoptosis in acute renal failure (ARF), we examined whether the attenuation of cisplatin-induced ARF is associated with the change in the degree of apoptotic cell death. The administration of cisplatin (CDDP) (6 mg/kg body weight) in rats induced ARF at day 5, as manifested by a significant increase in serum creatinine (Scr) and tubular damage. CDDP-induced apoptotic cell death was confirmed by electron microscopic examination, agarose gel electrophoresis, and increased cells positive for TaT-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) in the outer medulla of the kidney. Treatment with dimethylthiourea (DMTU)--a scavenger of hydroxyl radicals--or glycine abrogated CDDP-induced increases in Scr, the tubular damage score, and the number of TUNEL-positive cells. Pretreatment with uranyl acetate (UA) induced a significant expression of Bcl-2 in the kidney and ameliorated CDDP-induced increases in Scr, the tubular damage score, and TUNEL-positive cells in the outer stripe of the outer medulla. Our findings indicate (1) that the attenuation of CDDP-induced ARF was associated with less apoptotic cell death and (2) that the induction of the anti-apoptotic protein Bcl-2 attenuated apoptosis and tubular damage. Our results suggest that apoptotic cell death may play an important role in the development of cisplatin-induced ARF.

Acute Kidney Injury↗
PubMed1998

Glomerular injury induced by cationic 70-kD staphylococcal protein; specific immune response is not involved in early phase in rats.

A highly cationic staphylococal protein (designated p70, MW 70 kD, pI > 10) belongs to the groups of bacterial proteins that can bind immunoglobulin without specific antigen-antibody recognition; heparin inhibition tests indicated a charge interaction. This study evaluated the nephritogenicity of p70, which has affinity for the glomerular basement membrane (GBM), and the influence of various mediator systems on the induction of glomerulonephritis by p70. The left kidneys of intact rats, rats given cobra venom factor (complement-depleted), or rats given anti-adhesion molecules (ICAM-1 and LFA-1a) were perfused with p70. Proteinuria started within 24 h and persisted at day 5. Intraglomerular infiltration of cells was seen as early as 15 min, peaking at day 1. Deposits of rat IgG and C3 were seen in a subendothelial location 15 min after p70 perfusion in the left kidney and were found in a predominantly subepithelial location from 1 day onwards. Complement depletion and blockade of adhesion molecules suppressed proteinuria from day 2 onwards; these manipulations also prevented the recruitment of infiltrating cells and partially hindered the transfer of IgG across the GBM and the accumulation of IgG in the subepithelial region. In the non-perfused right kidneys, deposits of IgG and C3 were comparable to those in the left kidneys, suggesting that p70-IgG complexes formed in the circulation may also contribute to the deposits in the GBM. Heparin inhibition tests indicated an electrostatic interaction between p70 and immunoglobulin. Complement and inflammatory mediator systems (granulocytes, monocytes/macrophages, and/or lymphocytes) were required to provoke glomerular injury. p70 might play a role in acute glomerulonephritis following Staphylococcus aureus infection.

Animals↗
PubMed1998

Altered anionic GBM components in monoclonal antibody against slit diaphragm-injected proteinuric rats.

BACKGROUND: We previously reported that monoclonal antibody (mAb) 5-1-6 bound to renal filtration slits induces massive proteinuria without causing ultrastructural changes in the glomerulus. This study evaluated the underlying mechanisms of the increase in glomerular permeability. METHODS: The distribution of endogenous albumin and IgG in the glomerular basement membrane (GBM) was studied in in situ drip-fixed glomeruli of Munich-Wistar rats by use of immunogold immunocytochemistry in the presence and absence of mAb 5-1-6. The density of foot process glycocalyx components was estimated by labeling with Limax fluvus lectin- or Helix pomatia lectin-gold complexes. Anionic sites in the GBM were examined by labeling with cationic gold at pH 2.0 or 7.4. Carboxyl groups, which also furnish an anionic charge to the GBM, were examined by specific biotinylation and colloidal gold probe methods. In addition, the infusion-staining of anionic sites was performed by use of ruthenium red in both Munich-Wistar and Wistar rats. RESULTS: The urinary excretion of albumin and IgG was increased markedly in the treated rats, indicating a non-selective barrier defect. In the control rats, albumin and IgG molecules were mainly located along the inner half of the GBM, and to a lesser degree in the lamina rara externa. In the treated rats, the albumin and IgG moieties were more equally distributed throughout the width of the GBM. Newly appearing, small dense peaks at the outer side of the GBM were evident, indicating a barrier function of outer zone of the GBM and/or epithelial cell layer. No intergroup differences in the density of lectin binding sites on foot processes were seen. The reduction in the number of ruthenium red-positive anionic sites and cationic gold (pH 2. 0)-labeled anionic sites in the lamina rara externa was significant in the treated rats at day 3, indicating a possible alteration of charged proteoglycan in the lamina rara externa. No such changes were seen with cationic gold (pH 7.4)-labeled anionic sites in the GBM. The density of labeled carboxyl groups was significantly reduced in the treated rats relative to the controls. CONCLUSIONS: These results show that the injection of mAb 5-1-6 induced a perturbation of the charge- and probably the size-selective glomerular filtration barrier. The observed reduction in the levels of various negatively charged substances resulted in massive proteinuria, implying that alteration of target antigens can affect the integrity of the GBM constituents maintaining the normal barrier function.

Albuminuria↗
PubMed1998

A patient with thrombotic microangiopathy accompanied by glomerular subendothelial electron dense deposits.

A 50-year-old woman presented with thrombocytopenia, microangiopathic hemolytic anemia, and nephrotic syndrome. Although a high level of circulating immune complexes, mild hypocomplementemia, and the antinuclear antibody also were present, the criteria for collagen disease were not fulfilled. Renal biopsy demonstrated a typical thrombotic microangiopathy (TMA) involving glomeruli. There also were electron-dense deposits located just beneath the original glomerular basement membrane in the dilated subendothelial space, thought to be immune complexes following positive IgG, C1q and C3 staining on an immunofluorescent study. Corticosteroid therapy rapidly ameliorated her hematologic abnormalities and proteinuria and normalized the immunologic data. These findings strongly suggest that the TMA in this patient was induced by immune complex-associated mechanisms.

Biopsy↗
PubMed1998

Expression of types I, II, and III TGF-beta receptors in human glomerulonephritis.

Protein and mRNA expression of transforming growth factor-beta (TGF-beta) receptor type I (TbetaRI), type II (TbetaRII), and type III (TbetaRIII) were studied in serial sections of kidney samples obtained from patients with glomerulonephritis. In minimal change disease, weak expression of TbetaRI and TbetaRII was observed mainly in glomerular endothelial cells, peritubular capillaries, and interstitial arteriolar endothelial cells, whereas TbetaRIII expression was found mainly in the interstitium. Expression of all three TGF-beta receptors (TbetaR) was increased remarkably in glomerular and Bowman's capsular cells comprising the tuft adhesions to Bowman's capsules in glomerulonephritis with increased matrix accumulation, including IgA nephropathy, lupus nephritis, focal and segmental glomerulosclerosis, myeloperoxidase-antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis, and membranoproliferative glomerulonephritis. Increased expression of the three TbetaR was also seen in glomerular epithelial cells in the vicinity of glomerulosclerotic lesions, in crescent cells, and in some tubules and infiltrative mononuclear cells found in the periglomerular and tubulointerstitial lesions with increased matrix deposition. In contrast, no remarkable TbetaRII expression was noted in mesangial proliferative lesions in IgA nephropathy, lupus nephritis, and membranoproliferative glomerulonephritis. These data suggest that distinctive modulation of TbetaR expression may be involved in the development of adhesive, sclerotic, and proliferative renal lesions in human glomerulonephritis.

Activin Receptors, Type I↗
PubMed1997

Glomerular handling of immune complex in the acute phase of active in situ immune complex glomerulonephritis employing cationized ferritin in rats. Ultrastructural localization of immune complex, complements and inflammatory cells.

The ultrastructural localization of immune complex (IC) and inflammatory mediator systems in the glomerulus was investigated in active in situ IC glomerulonephritis employing cationized ferritin in rats. Glomerulonephritis was induced by unilateral renal perfusion of cationized ferritin as antigen (Ag) in preimmunized rats, and anti-ferritin antibody (Ab), C3 and the rat C5b-9 complex were localized by means of immunogold electron microscopy. Ag-Ab complexes were initially formed subendothelially, associated with C3, and attracted platelets, polymorphonuclear leucocytes (PMN) and monocytes. Then Ag-Ab complexes, without C3, passed across the glomerular basement membrane to re-aggregate subepithelially accompanied by C3 deposition after 1 day. Ag-Ab complexes without C3 accumulated in the inter-podocyte space within 1 day and were seen in the epithelial cells at 6 h. C5b-9 complexes were found in subepithelial immune deposits and in membrane vesicles of the epithelial cells, but only in very small amounts in subendothelial immune deposits. Accumulated platelets, PMN, and monocyte were in direct contact with endothelial cells or subendothelial IC. PMN and monocytes contained Ag, Ab and C3 in intracytoplasmic vacuoles. Ag-Ab complexes were also found in the mesangial matrix adjacent to the subendothelial region after 2 h and increased slightly in number, with expansion of the mesangial area thereafter. Most ICs formed in the subendothelial space rapidly formed lattices of a size that activated C3 and were then translocated to the subepithelial space. The potential ability of C3 to solubilize ICs in the subendothelial region may be important in this process. Endocytosis of subendothelial ICs by PMN and/or monocytes and the movement of ICs to the mesangial matrix may also contribute to the removal of IC from the subendothelial space.

Acute-Phase Reaction↗
PubMed1997

Studies on the site of renal tubular defect in Bartter's syndrome.

Renal tubular function was studied in an 8-month-old male infant with Bartter's syndrome, which is characterized by hypokalemic metabolic alkalosis, normotensive hyperreninemic hyperaldosteronism, and reduced pressor response to angiotensin II. Chloride transport along the diluting segment (CH2O/CH2O + CCl) was impaired. Furthermore, furosemide did not elicit normal natriuresis, which suggested impaired chloride reabsorptive capacity at the furosemide-sensitive ascending limb of Henle's loop. Loss of antidiuretic hormone-mediated urinary concentration was in support of this. These findings pointed to the thick ascending limb of Henle's loop as the site of the primary defect in this child.

Bartter Syndrome↗
PubMed1996

Structural continuity of filtration slit (slit diaphragm) to plasma membrane of podocyte.

Murine monoclonal antibody 5-1-6 was reported to bind to the slit membrane and closely related structures in rat renal glomeruli; it induced heavy, reversible proteinuria and appeared to redistribute onto the plasma membrane of epithelial cells after binding at the original target sites. This phenomenon of antigenic movement has not been analyzed in detail to date. In addition to normal kidneys we also studied localization of the antigen recognized by monoclonal antibody 5-1-6 in protamine sulfate-perfused rat kidneys, in which slit diaphragms are known to be functionally modified. Isolated glomeruli as well as ultrathin kidney cryosections were labeled by the immunogold technique to clarify the relation between this antigen and the slit diaphragm. Sequential localization of injected monoclonal antibody was visualized using a post-embedding immunogold method in rats 2 hours to 12 days after injection of antibody. Ultrastructural immunogold labeling demonstrated that under normal conditions antigenic molecules were expressed mainly in the area beneath the slit diaphragms. Occasionally labeling was found at the base of the foot process, facing the glomerular basement membrane. After protamine sulfate treatment antigenic sites were dislocated due to the lifting and disruption of slit diaphragms, indicating that this antigen is associated with slit diaphragms. Injected antibody was localized at the filtration slits at 2 hours, and by 12 hours it had moved onto the apical plasma cell membrane of foot process. In addition, from 3 days onwards patch or cap-like formation on the plasma cell membrane of podocytes was seen. Possible shedding of antibody from podocyte cell surface membrane was occasionally encountered, but internalization of antibody was a minor event. Elution experiments in isolated glomeruli at day 3 indicated that antigen and antibody were both localized on the podocyte cell surface membrane, suggesting redistribution of immune complexes. In conclusion, filtration slits (slit diaphragms) and the apical membrane of foot process of podocytes demonstrate structural continuity, as revealed by the movement of the antigen recognized by monoclonal antibody 5-1-6 as antigen-antibody complexes.

Animals↗
PubMed1996

Anti-DNA antibody derived from a systemic lupus erythematosus (SLE) patient forms histone-DNA-anti-DNA complexes that bind to rat glomeruli in vivo.

Histone can mediate the binding of both free DNA and DNA complexed to anti-DNA antibody to the glomerular capillary wall. We tested whether performed histone-DNA-anti-DNA immune complexes (IC) could bind to the glomerular capillary wall. The immune complex, generated with anti-DNA antibody derived from an SLE patient and excess of 125I-DNA followed by digestion with DNase, was mixed with histones. The complex containing 4 micrograms DNA was injected via the aorta into the left kidney of rats. At 15 min, 1-3% of the histone-DNA-anti-DNA antibody complex bound (measured as 125I-DNA), when histone was omitted less than 0-1% of the DNA-anti-DNA antibody complex bound. By immunofluorescence human immunoglobulins and histones, representing the IC, could be observed in a capillary pattern; but no complement deposition was detected. Electron microscopy revealed discrete, electron dense deposits in a subendothelial, subepithelial and mesangial localization at 15 min. These results provide direct evidence that antibodies from serum of SLE patients can form soluble histone-DNA-anti-DNA immune complexes that bind to the glomerular capillary wall in vivo.

Animals↗
PubMed1996

Reliability and validity of the Japanese version of Job Content Questionnaire: replication and extension in computer company employees.

In order to investigate the reliability and validity of selected scales from the Japanese version of Job Content Questionnaire (JCQ, Karasek 1985), a survey was conducted of 1,126 employees of a computer company in Japan using a questionnaire including 31 items from the JCQ. Ten JCQ scales on psychological and physical demands were examined in 603 male and 84 female respondents. Cronbach's alpha reliability coefficients for nine JCQ scales which consisted of two or more items ranged from 0.66 to 0.90 for males and from 0.64 to 0.88 for females. Item factor analysis for each scale indicated that the first factor explained 50 or more percent of item variation of decision authority, supervisor support, coworker support and Framingham physical exertion in males and females and of psychological demands in females. The skill discretion, decision authority and decision latitude significantly and positively correlated with age, years of employment and years of experience in males (p < 0.05). The decision authority significantly and positively correlated with age and years of experience in females (p < 0.05). Psychological demands, Framingham demand and physical exertion significantly and positively correlated with overtime in males and females (p < 0.05). Skill discretion, decision authority and decision latitude, psychological demands and Framingham demand were lowest in computer equipment operators; physical exertion and Framingham physical exertion were lowest in computer software engineers/technicians. It is suggested that these JCQ scales are reliable and valid instruments for assessing job stressors in computer company employees in Japan.

Adult↗
PubMed1996

Time series investigation of job-events and depression in computer software engineers.

The aim of the present study is to conduct an observation of a time series of job-event/life event and depressive symptoms, prospectively. Ten male computer software engineers were observed every two weeks for five months and every following week for two months. In total, one hundred and eighty-one observations were made. A semi-structured interview was conducted to survey the week-unit job-events on each sampling day. The depressive symptoms were measured using Zung's Self-reporting Depressive Scale (SDS). It was found that the events had a significant effect on the SDS raw score. It also showed that the effective time period of the events on depression is within two weeks. With a week-based analysis in a prospective approach, the present study showed the immediate effects of job events or life events on depressive symptoms.

Adult↗
PubMed1995

Successful treatment of invasive thoracopulmonary mucormycosis in a patient with acute lymphoblastic leukemia.

BACKGROUND: Pulmonary mucormycosis associated with hematologic malignancy is an uncommon, but important opportunistic fungal pneumonia that is usually a fatal infection. Only a few survivors of pulmonary mucormycosis have been reported. METHODS: A case report of invasive thoracopulmonary mucormycosis during remission-induction therapy for acute lymphoblastic leukemia and a review of the literature are presented. RESULTS: The fungal lesions extended to both lungs, the left ribs, and intercostal muscles. Percutaneous needle biopsy and immunostaining of the fungal hyphae established the diagnosis of thoracopulmonary mucormycosis. The patient was treated with granulocyte-colony stimulating factor (G-CSF) and intravenous amphotericin B for 9 weeks and the lesions in the right lung disappeared. Left pneumonectomy and partial resection of the chest wall were later performed. The left lung was grossly necrotic and contained a large cavity and bronchopulmonary fistula. Thereafter, antileukemic therapy was resumed and completed without recurrence of mucormycosis or leukemia. CONCLUSIONS: In the management of mucormycosis, the addition of G-CSF to the conventional treatment may substantially improve outcome.

Adolescent↗
PubMed1995

Complement system promotes transfer of immune complex across glomerular filtration barrier.

BACKGROUND: The solubilizing effect of complement (C) on immune complexes (IC) in the fluid phase is well known, however effects on tissue-deposited IC have not been analyzed in detail. We studied the influence of C depletion on the movement of IC across the glomerular basement membrane in a rat model of passive in situ IC nephritis. EXPERIMENTAL DESIGN: The left kidneys of intact rats, rats given cobra venom factor (C-depleted) or rats given anti-polymorphonuclear granulocyte antiserum (PMN-depleted) were perfused with cationized ferritin (electron-dense tracer antigen), followed by intravenous injection of rabbit anti-ferritin antibody 15 minutes later. The glomerular distribution of rabbit IgG (antibody) and rat C3 was visualized by immunogold staining. RESULTS: In intact, nephritic rats (non C-depleted), the distribution of antigen, antibody, and C3 (IC) was mainly subendothelial 2 and 6 hours after antibody injection, at 24 hours about 75% and by 48 hours virtually all 3 IC components were localized on the subepithelial side of the glomerular basement membrane in all glomeruli. In C-depleted rats, the distribution of IC was as in intact rats, up to 6 hours. At 24 hours, two patterns of IC distribution within individual glomeruli could be distinguished. About 2/3 of the capillary wall area revealed a distribution similar to the C-intact animals; however in 1/3 of the capillary wall area, IC was still predominantly subendothelial at 24 hours. By 48 hours, some accumulation in the lamina densa was noted. At day 7, some IC was still subendothelial, in limited areas, even though serum C3 level had returned to 60% of normal. On the other hand, the distribution of IC in polymorphonuclear leukocyte-depleted, C-intact rats, showed no difference to that in control nephritic rats. Proteinuria was significantly decreased in both C-depleted rats and polymorphonuclear leukocyte-depleted rats. Thus, enhanced glomerular permeability itself does not guarantee complete, rapid IC movement. CONCLUSIONS: The C system promotes effective transfer of IC across the glomerular basement membrane, probably due to the solubilizing effect of C on IC lattices.

Animals↗