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Biomedical subjects

Akira Hishida

Publications and source records attributed to Akira Hishida.

At least 91 records · Page 5Linked to original sources
PubMed2003

Influence of body composition on 5 year mortality in patients on regular haemodialysis.

BACKGROUND: Reduction of body mass index (BMI) significantly affects mortality in haemodialysis (HD) patients, but it remains to be determined which of the body components influences mortality. METHODS: We examined the whole body composition of 262 HD patients by dual-energy X-ray absorptiometry (DEXA) (age: 60+/-12 years; HD duration 9+/-7 years; male/female: 177/85; diabetics, n=50) and subsequently followed mortality for 5 years. RESULTS: Patient age was significantly correlated with limb/trunk lean mass (LTLM) ratio (r=-0.350, P<0.01) and % fat content in whole tissue (r=0.145, P=0.02). There was a significant positive relationship between LTLM ratio and serum creatinine both in males (r=0.404, P<0.01) and females (r=0.267, P=0.01). Diabetic males and females both had a significantly lower LTLM ratio than non-diabetic males (P<0.01) and females (P<0.04). During the 5 years, 65 patients (24.8%) died mainly of cardiovascular diseases and infections. BMI was lower in the expired group than in survivors (P<0.04). LTLM ratio was significantly reduced in the expired group compared with the surviving males (0.629+/-0.097 vs 0.707+/-0.094; P<0.01) and females (0.611+/-0.101 vs 0.651+/-0.078; P<0.01). Cox's proportional hazards analysis revealed that the reduction of LTLM ratio was a significant determinant of death in men (P<0.01), while a lower percentage of fat content of trunk was a significant determinant of death in women (P<0.01). In contrast, BMI did not influence mortality in either sex. CONCLUSIONS: Measurements of regional lean and fat mass volumes by DEXA may be useful for predicting death in patients receiving long-term HD.

Absorptiometry, Photon↗
PubMed2003

Blood 8-hydroxy-2'-deoxyguanosine is associated with erythropoietin resistance in haemodialysis patients.

BACKGROUND: 8-Hydroxy-2'-deoxyguanosine (8-OHdG), a product of oxidized DNA, is increased in haemodialysis (HD) patients, but the clinical relevance of enhanced 8-OHdG production in these patients remains unknown. METHODS: We cross-sectionally measured serum 8-OHdG in 73 patients on maintenance HD (age 68+/-2 years, time on HD 85+/-11 months, male/female=42/31), and examined the relationship between blood 8-OHdG and the severity of renal anaemia and the weekly dosage of recombinant human erythropoietin (rHuEPO). RESULTS: There was a significant increase in serum 8-OHdG in HD patients compared with normal subjects. Serum 8-OHdG was positively correlated with the patients' age (r=0.231, P<0.05) but not with the duration of HD. Serum 8-OHdG was significantly higher in diabetic subjects than in non-diabetic subjects (P<0.05). Serum 8-OHdG had a significant inverse correlation with haemoglobin (Hb) (r=-0.526, P<0.01) but a positive correlation with the rHuEPO dose (r=0.443, P<0.01) and the ratio of the weekly rHuEPO dose divided by Hb (r=0.487, P<0.01). Serum 8-OHdG was not correlated with inflammatory and nutritional parameters. CONCLUSIONS: These findings suggest that the elevation of circulating 8-OHdG may be associated, at least in part, with rHuEPO resistance in HD patients.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

A case of thrombotic microangiopathy complicated with systemic lupus erythematosus.

A woman was admitted to the hospital with joint pain. She was also found to have pericardial effusion, renal dysfunction, pancytopenia, and positive antinuclear antibody; a diagnosis of systemic lupus erythematosus (SLE) was made. Although she had neither neurological symptoms nor fever, laboratory tests showed microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction. Therefore, we diagnosed her illness as SLE complicated by thrombotic microangiopathy (TMA). Plasmapheresis was performed in addition to immunosuppressive therapy. TMA improved rapidly and renal function improved gradually. The number of patients with SLE complicated by TMA is relatively small and the mortality rate is extremely high. A diagnosis of TMA is difficult to determine in patients with SLE because of the overlapping clinical symptoms. The data suggest that prompt induction of plasmapheresis in addition to immunosuppressive therapy is necessary in SLE patients having symptoms suspicious of TMA even before they fulfill the 5 symptoms typical of TMA.

Anemia, Hemolytic↗
PubMed2003

A mechanism for the development of subepithelial deposits in a patient with type III membranoproliferative glomerulonephritis.

We report on a patient with membranoproliferative glomerulonephritis (MPGN) type III, whose repeated renal biopsies show evolution from a type I-like pattern to a type III pattern of immune complex formation over a 1-year period. Based on the development of experimental in situ immune complex glomerulonephritis, we discuss possible mechanisms for the formation of subepithelial deposits in type III MPGN with reference to an experimental in situ immune complex model of glomerulonephritis.

Adult↗
PubMed2003

Ultrastructure of tubular epithelial cells in response to microembolism-induced chronic ischemic injury in rats.

BACKGROUND: Loss of polarization of proximal tubular epithelial cells (PTECs) with detachment is known as an early response of PTEC to acute ischemia during acute tubular necrosis. However, the early morphologic changes of PTECs to chronic ischemic injury are not clear. We previously reported that rat renal microembolism induced chronic tubulointerstitial ischemia and extensive proximal tubular atrophy. Among atrophic tubules, some tubules showed a peculiar pattern mixed with intact and atrophic epithelial cells, which was thought to be the earliest feature leading to atrophic tubules. METHODS: Chronic ischemic injury was induced by the left renal perfusion of microspheres after removal of the right kidney in rats. The ultrastructual changes, especially focusing on the process of tubular atrophy, are examined by electron microscopy after 4, 8 and 12 weeks. RESULTS: Early changes in PTECs showed slight simplification or dedifferentiation such as loss or diminution of basolateral infolding and microvilli. Moderately simplified PTECs were partially detached from the tubular basement membrane (TBM) with matrix production in the detached spaces but maintained cell-cell contacts between PTECs. In the advanced stage, severely simplified PTECs showed complete detachment from TBM and more atrophic features characterized by cobblestone appearance with a uniform attachment between cells. In concert with these PTEC changes, accumulation of interstitial fibroblast-like cells (FLCs) with collagenous matrices could be found first in the interstitial spaces and later in the spaces where PTECs detached from TBM. CONCLUSION: Our results suggest that microembolism-induced chronic ischemic injury induces PTEC dedifferentiation and detachment from TBM with matrix production in concert with FLC activation, resulting in tubulointerstitial damage characterized by tubular atrophy and renal fibrosis.

Animals↗
PubMed2003

Cytomegalovirus colitis following immunosuppressive therapy for lupus peritonitis and lupus nephritis.

We report a woman with lupus nephritis complicated with lupus peritonitis and cytomegalovirus (CMV) colitis. Diagnosis of lupus peritonitis was made by abdominal computed tomography scan, colonoscopy, and ascitic fluid analysis. Steroid and cyclophosphamide therapy resulted in the improvement of severe lupus nephritis and peritonitis. Thereafter, she developed multiple colonic ulcers as diagnosed by colonoscopy and positive CMV antigenemia assay. Treatment with ganciclovir resulted in the disappearance of colonic lesions. The low cluster of differentiation (CD)4+ lymphocyte count (41/mm3) suggested that the cell-mediated immunity of this patient was comparable to that seen in patients with acquired immunodeficiency syndrome (AIDS).

Adult↗
PubMed2003

A Japanese case of familial Mediterranean fever with family history demonstrating a mutation in MEFV.

We describe a 17-year-old woman with a family history of FMF who suffered from recurrent fever accompanied by pains in the left chest and abdomen. During a five-year period she experienced attacks about once every six months. The metaraminol provocative test was positive. Genomic DNA extracted from peripheral blood lymphocytes from both her and her parents were analyzed by polymerase chain reaction (PCR), followed by cycle sequencing. We detected a mutation (ATG to ATA) in codon 694 in exon 10 of the FMF gene, MEFV, that resulted in a substitution of isoleucine for methionine (M6941) in both her and her father. This is the first Japanese case of FMF with a mutation in MEFV identified in the family history.

Adolescent↗
PubMed2002

Thrombotic thrombocytopenic purpura associated with mixed connective tissue disease.

We report a male case of thrombotic microangiopathy with mixed connective tissue disease (MCTD). Thrombocytopenia and hemolytic anemia developed despite steroid treatment for acute interstitial pneumonitis. The patient became confused and eventually developed coma. Diffusion-weighted MRI revealed high intensity at the brainstem, frontal lobes, basal nuclei, and insula, findings compatible with multiple brain edema due to microthrombosis. Despite the treatment of successive plasma exchange and steroid pulse therapy, he eventually died by multiple organ failure. This rare case suggested that diffusion-weighted MRI is very sensitive at detecting early alterations of thrombotic thrombocytopenic purpura (TTP)-induced ischemic lesions in the brain. Neuropsychiatric symptoms due to thrombotic microangiopathy could be some of the fatal complications in MCTD patients.

Brain↗
PubMed2002

Transient leukopenia and anaphylatoxin production during granulocyte apheresis as treatment for ulcerative colitis.

It is well known that transient leukopenia due to activation of the alternative pathway of the complement system accompanies hemodialysis when cellulose acetate dialyzers are used. However, it has not been evaluated whether leukopenia also occurs during granulocyte apheresis (GCAP) as treatment for ulcerative colitis, in which an extracorporeal column is filled with cellulose acetate beads in order to remove circulating leukocytes. The aim of the present study was to evaluate whether transient leukopenia and activation of the alternative pathway of the complement system were observed during GCAP. In 8 patients undergoing GCAP weekly for 10 weeks, circulating leukocyte counts and plasma concentrations of C3a, a product of the activated alternative pathway of the complement system, were determined. GCAP elicited a rapid decline in the number of circulating leukocytes to 61.8 +/- 13.8% of the baseline value after 15 minutes of GCAP (P < 0.02). Thereafter, the number of circulating leukocytes returned to approximately baseline after 60 minutes. The baseline plasma C3a concentration was 123 +/- 61 ng/mL, and a significant increase to 425 +/- 123 ng/mL was observed after 15 minutes of GCAP (P < 0.02). The plasma C3a concentration reached 417 +/- 96 ng/mL after 60 minutes (P < 0.02). It thus follows that GCAP activates the alternative pathway of the complement system, resulting in anaphylatoxin production.

Adult↗
PubMed2002

Transforming growth factor-beta receptors in self-limited vs. chronic progressive nephritis in rats.

Increases in transforming growth factor-beta (TGF-beta) expression and extracellular matrix accumulation are transient in acute self-limited mesangial proliferative glomerulonephritis induced by a single injection of anti-thymocyte serum (ATS), while these increases persist following repeated injections that produce chronic progressive sclerosing glomerulonephritis with tubulointerstitial lesions. However, little is known about the expression of TGF-beta receptors (TbetaRs) in cells involved in the proliferative and sclerosing renal lesions. A study of protein and mRNA expression for type I (TbetaRI), type II (TbetaRII), and type III (TbetaRIII) TbetaR in both forms of nephritis was therefore carried out by immunohistochemistry and in situ hybridization. Inhibition of cell proliferation and stimulation of matrix production by TGF-beta1 were assessed in isolated glomeruli using [(3)H]thymidine incorporation and [(3)H]proline metabolic labelling, respectively. In acute self-limited nephritis, expression of TbetaRI, TbetaRII, and TbetaRIII increased in the glomerular and Bowman's capsular epithelial cells comprising the glomerular tuft adhesions to Bowman's capsules. However, TbetaRII expression was not prominent in proliferating mesangial cells. Glomeruli isolated from rats with acute self-limited nephritis at day 7, when mesangial cell proliferation was maximal, were partially resistant to the mitoinhibitory effects of TGF-beta1. In contrast, expression of all three TbetaRs was elevated in glomerular and tubulointerstitial lesions in chronic progressive nephritis, and glomeruli isolated from rats with chronic progressive nephritis 7 days after the second ATS injection were sensitive to TGF-beta1. These data suggest that distinct cellular responses to TGF-beta1 resulting from differential expression of TbetaR underlie the difference between acute self-limited mesangial proliferative and chronic progressive sclerosing ATS nephritis in the development of proliferative and sclerotic renal lesions.

Acute Disease↗
PubMed2002

Effects of dietary lipids on daunomycin-induced nephropathy in mice: comparison between cod liver oil and soybean oil.

Although it is well known that dietary lipids affect the course of glomerulonephritis in rats and humans, the precise mechanisms involved have not been fully elucidated. The aim of this study was to investigate the effects of different types of dietary lipids (fish oil and vegetable oil) on daunomycin (DM)-induced nephropathy in mice fed on soybean oil (SO) or cod liver oil (CLO). Urinary protein excretion, serum albumin, creatinine, total cholesterol, and TG were measured, and glomerular histological changes were evaluated. Antioxidant enzymes were also measured, along with the levels of lipid peroxide, GSH, thromboxane (Tx) B2, and 6-keto prostaglandin F1alpha in renal cortical tissue. Dietary CLO significantly reduced urinary albumin excretion and ameliorated the histological changes induced by DM. The increase of tissue lipid peroxide levels seen in SO-fed mice was suppressed in CLO-fed mice, whereas CLO-fed mice showed higher GSH levels than SO-fed mice throughout the experiment. In addition, renal tissue GSH peroxidase activity was significantly higher at 72 h after DM injection in CLO-DM mice than in SO-DM mice. Both renal cortical TxB2 and 6-keto PGF1alpha levels were significantly lower in CLO-DM mice than in SO-DM mice. These results suggest that inhibition of oxidative damage by dietary CLO played an important role in the prevention of DM nephropathy in this mouse model. The effect of CLO was closely associated with the inhibition of Tx synthesis.

Albuminuria↗
PubMed2002

Mycophenolate mofetil inhibits regenerative repair in uranyl acetate-induced acute renal failure by reduced interstitial cellular response.

We recently reported that transient appearance of interstitial myofibroblasts and infiltrating macrophages might play a role in cellular recovery in uranyl acetate (UA)-induced acute renal failure (ARF). Here we tested the effects of mycophenolate mofetil (MMF), which attenuates infiltration of lymphocytes, macrophages, and myofibroblasts, but does not suppress epithelial regeneration, on renal tissue repair. Rats treated with MMF (20 mg/kg/day) or vehicle were sacrificed at 2, 5, and 7 days after induction of ARF by injection of 5 mg/kg UA. Renal tissues were immunostained for bromodeoxyuridine (BrdU) and Ki67, alpha-smooth muscle actin (alpha-SMA), ED1, and CD43. The expression levels of alpha-SMA mRNA were examined by reverse transcription-polymerase chain reaction. Body weight loss or serum albumin levels were similar in MMF and vehicle rats during the experiment. In vehicle group, serum creatinine (Scr) significantly increased after day 5, but proximal tubular (PT) damage score increased as early as day 2 after UA injection. BrdU- or Ki67-positive regenerating tubular cells, ED1-positive macrophages and alpha-SMA-positive myofibroblasts significantly increased in the interstitium after day 5. In MMF-treated rats, Scr and PT damage score significantly increased at day 7 and the number of regenerating PT were significantly reduced compared with vehicle-treated rats at days 5 and 7. The numbers of macrophages and myofibroblasts and the expression of alpha-SMA mRNA were significantly lower in MMF than in vehicle rats at day 5, indicating that reduced interstitial cellular response is linked to the inhibition of regenerative repair. CD43-positive lymphocytes were significantly reduced in MMF group than in vehicle group at day 7, suggesting that lymphocyte infiltration does not seem to contribute to early regenerative response of proximal tubules. The transient appearance of myofibroblasts and macrophages in the interstitium may promote regenerative repair in UA-induced ARF in rats.

Actins↗
PubMed2002

Association between interleukin-6 and carotid atherosclerosis in hemodialysis patients.

BACKGROUND: Interleukin-6 (IL-6) is associated with cardiovascular complications in general subjects. Although blood IL-6 is greatly elevated in hemodialysis (HD) patients, the role of IL-6 in the advance of atherosclerosis remains to be determined. METHODS: We conducted a cross-sectional study to investigate the relationship between circulating IL-6 and carotid atherosclerotic changes in 156 HD patients (age 58 +/- 1 years; time on HD treatment 13 +/- 1 years; 97 males and 59 females). Serum IL-6, IgG and IgA titers of Chlamydia pneumoniae antibodies, the intima-media thickness (IMT) and the cross-sectional intima-media area (IMarea) of the carotid arteries were measured by ultrasonography in each patient. RESULTS: Serum IL-6 levels were significantly higher in HD patients (2.04 +/- 0.16 pg/mL) compared to normal age-matched control subjects (0.31 +/- 0.06 pg/mL, N = 24). Circulating log IL-6 levels were positively correlated with IMT (r = 0.278, P < 0.01) and IMarea (r = 0.344, P < 0.01), respectively. A stepwise multiple regression analysis revealed that IL-6 became significant predictors for IMT and IMarea but not for aortic wall calcification at L2/3 vertebrae. Serum log IL-6 was significantly correlated with IgG (r = 0.277, P < 0.01) and IgA titers of anti-Chlamydia antibodies (r = 0.192, P < 0.02). Serum IgA anti-Chlamydia titers were also correlated with the maximal diameter of carotid plaque (r = 0.293, P < 0.04). CONCLUSIONS: These findings suggested that IL-6 is associated with the severity of carotid atherosclerosis in HD patients. Persistent chronic chlamydial infection may be related, in part, to the advance of carotid plaque enlargement in dialysis patients.

Adult↗
PubMed2002

Renal tubulointerstitial injury in weanling rats with hyperhomocysteinemia.

BACKGROUND: While hyperhomocysteinemia is associated with an increased risk of atherosclerosis and the related cardiovascular diseases, the effect of hyperhomocysteinemia on the kidney has not been clearly demonstrated. The purpose of this study was to investigate whether long-term hyperhomocysteinemia develops atherosclerotic lesions in the kidney. METHODS: The effects of various dietary combinations, including folate deficiency, choline deficiency and methionine loading, on the plasma homocysteine concentration, renal function and renal histopathology were examined for 12 weeks in male weanling Fisher rats. RESULTS: Folate deficiency, choline deficiency and methionine loading synergistically induced hyperhomocysteinemia up to 69.7 +/- 23.1 micromol/L (control, 11.6 +/- 3.9 micromol/L, P < 0.01) without any change in blood pressure. Creatinine clearance was negatively correlated with the plasma homocysteine concentration (r = -0.55, P < 0.01). Arterial and arteriolar wall thickening, and focal tubulointerstitial fibrosis were found in the kidneys of the hyperhomocysteinemic rat. The lesions of tubulointerstitial fibrosis appeared striped or wedge-shaped at the subcapsular cortex of the kidney. In addition, the expression of vascular endothelial growth factor, an indicator of hypoxia, was increased in the adjacent more intact area of the cortex. These findings suggest that the renal tubulointerstitial lesions were likely to be mediated by severe ischemia due to regional circulatory disturbance. Folate supplementation diminished these vascular and tubulointerstitial changes. CONCLUSION: These results indicate that diet-induced chronic hyperhomocysteinemia could induce vascular remodeling and tubulointerstitial injury in the kidney, and that these changes were ameliorated by folate supplementation.

Age Factors↗
PubMed2002

Membranous glomerulonephritis associated with renal cell carcinoma: failure to detect a nephritogenic tumor antigen.

A 57-year-old man with renal cell carcinoma associated with membranous glomerulonephropathy (MGN) developed a transient amelioration of the nephrotic syndrome after excision of the tumor. We tried to identify a nephritogenic tumor antigen using the immunoblotting technique in this patient with MGN, since previous studies examined the interaction between tumor antigens and IgG eluted from the kidney tissue using immunofluorescence or immunodiffusion techniques, and no studies have identified the specific tumor antigen with the immunoblotting method. In the present study, no significant immunoreactivity was noted between the IgG eluted from renal cortical tissues of the patient and renal cell carcinoma proteins. Further studies are necessary to establish the pathogenic mechanism of MGN associated with malignancy.

Antibody Specificity↗
PubMed2002

Potassium-lowering effect of mineralocorticoid therapy in patients undergoing hemodialysis.

The present study was conducted to examine potassium lowering effect of exogenous mineralocorticoid (fludrocortisone acetate; FCA) administration to the patients with chronic renal failure undergoing hemodialysis. Fifteen patients on hemodialysis receiving FCA with its dosage gradually increased from 0 to 0.20 mg/day were observed for five successive 4-week periods. The serum potassium concentration was significantly decreased after FCA administration concomitant with the decrease of the salivary sodium to potassium ratio. Such decrease in serum potassium concentration was more significant in patients with <150 pg/ml of plasma aldosterone concentration (PAC) (low PAC group) than in those with >/=150 pg/ml of PAC (high PAC group). 0.05 mg of FCA was sufficient to lower serum potassium in low PAC group, while 0.15 mg of FCA was required for high PAC group. FCA administration did not affect serum sodium, chloride and bicarbonate concentrations. Body weight and blood pressure were not increased during the experimental periods. There were no significant changes in plasma level of glucose, insulin, epinephrine and norepinephrine. These results suggested that FCA could be effective to treat hyperkalemia without any adverse effects in patients undergoing hemodialysis.

Adult↗