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Biomedical subjects

T Fujita

Publications and source records attributed to T Fujita.

At least 163 records · Page 9Linked to original sources
PubMed2001

Regulatory effects of senescence marker protein 30 on the proliferation of hepatocytes.

Senescence marker protein 30 (SMP 30) is preferentially expressed in the liver. One of its remarkable functions is the protection of cells against various injuries by enhancement of membrane calcium-pump activity. We analyzed the role of SMP 30 in hepatocyte proliferation. SMP 30 expression was decreased initially, then increased along with hepatic regeneration, after carbon tetrachloride (CCl4) administration. SMP 30 expression was decreased in the necrotic phase and then gradually increased. Its increase was slightly delayed just after the mitotic phase. These results lead us to speculate that mitoses of hepatic cells induce enhanced SMP 30 expression. In contrast, administration of lead nitrate (LN) as a hepatic mitogen induced a more stable increase of SMP 30 expression. To estimate the effect of SMP 30 on cell proliferation, we evaluated hepatic mitosis in wild-type and SMP 30-deficient knockout (KO) mice after CCl4 administration. We found an increase in mitotic numbers in hepatocytes of KO mice. This result suggests that SMP 30 has a suppressive effect on cell proliferation. Suppressive activity of SMP 30 cDNA was shown in cultured hepatoblastic cells. Our results suggest that SMP 30 performs a regulatory function in liver regeneration.

Animals↗
PubMed2001

Contact pressure distribution in the supine position in low-birth weight infants analyzed by a photoelastic method.

BACKGROUND: Contact pressure distribution patterns in the supine position in low-birth weight (LBW) neonates were analyzed by the use of a photoelastic method. METHODS: A total of 61 subjects (LBW neonates, mature (bodyweight > 2,500 g at birth) neonates, normal infants and Down syndrome (DS) infants) were selected for the study. Infants were placed on a photoelastic measuring table. Photoelastic images generated in the contact regions of the body were photographed with a camera and printed on monochrome paper. The coefficient of variation in the pressure distribution value (PcV) and the top and bottom ratio (mu) of the trunk at the center of pressure were calculated. RESULTS: The Pcv value was significantly lower in DS than LBW (P < 0.001), mature (P < 0.002) and normal infants (P < 0.01). The mu value in LBW and mature neonates was 48.9 and 50.2%, respectively. Normal infants had a mu value of 44.0%, which was significantly lower than that in LBW neonates. However, there was no significant difference between LBW and DS infants. CONCLUSIONS: Neurological impairment specifically affects the data obtained by photoelastic analysis.

Body Weight↗
PubMed2001

Clusterin is up-regulated in glomerular mesangial cells in complement-mediated injury.

BACKGROUND: Clusterin is a soluble complement regulatory protein that binds to C5b-7 and inhibits generation of membrane attack complex, C5b-9. Glomerular deposition of clusterin has been observed in human and experimental membranous nephropathy in association with C5b-9 and immune deposits. However, it is controversial as to whether clusterin observed in glomeruli is synthesized by the resident glomerular cells or is derived from the circulation. We examined whether clusterin is expressed by resident glomerular cells exposed to complement-mediated injury. METHODS: In vitro, cultured mesangial cells were exposed to antithymocyte serum immunoglobulin G and 5% normal rat serum as a complement source. In vivo, we induced anti-Thy1 nephritis in rats and examined the kidneys on days 8 and 29. RESULTS: We observed increased expression of clusterin in cultured rat glomerular mesangial cells stimulated by sublytic complement attack. We also demonstrated that in comparison with control rats, both a marked increase in clusterin mRNA in the glomeruli and marked deposition of clusterin protein in the mesangial area occurred in the OX-7-treated rats on day 8 in association with C5b-9 deposition and on day 29. CONCLUSION: Clusterin was induced in glomerular mesangial cells during the course of immune-mediated injuries. This up-regulation of clusterin may play a critical role in protecting mesangial cells from complement attack.

Animals↗
PubMed2001

Influence of various hemodialysis membranes on the plasma (1-->3)-beta-D-glucan level.

BACKGROUND: Recently, invasive fungal infections have increased significantly because of the growing number of immunocompromised hosts. The measurement of plasma (1-->3)-beta-D-glucan has been proposed as a useful diagnostic tool for deep mycosis. In this study, we analyzed the alteration of the plasma (1-->3)-beta-D-glucan concentration by using different kinds of hemodialysis (HD) membranes in end-stage renal disease (ESRD) patients and estimated its half-life. METHODS: Twenty-seven patients with ESRD without known fungal infections (with a median age of 66 years old) were enrolled in this study. Cellulose triacetate (CTA) membrane, cellulose (Cu) membrane, and polymethyl methacrylate (PMMA) membrane were used in three consecutive initiations of HD and plasma (1-->3)-beta-D-glucan concentration was measured before and after each HD session. RESULTS: The level did not change between before and after HD when CTA and PMMA membranes were used. In contrast, the plasma (1-->3)-beta-D-glucan level increased greatly after HD using the Cu membrane (from 9.4 to 332 pg/mL in median). Hypothesizing that the plasma (1-->3)-beta-D-glucan level declines exponentially, its median half-life is estimated at 20 hours, which is not affected by hepatic or renal function. CONCLUSIONS: Because the plasma (1-->3)-beta-D-glucan level increases dramatically after HD using the Cu membrane, dialyzers with Cu membrane should be avoided for HD in patients with suspected deep mycosis. The measurement of plasma (1-->3)-beta-D-glucan is also useful for the patients with hepatic or renal failure.

Adult↗
PubMed2001

Hepatitis C virus in blood and dialysate in hemodialysis.

The prevalence of hepatitis C virus (HCV) positivity among hemodialysis patients remains high compared with that of the healthy population, and thus the issue of safety and environmental protection must be addressed. The purpose of this study is to evaluate the dynamics of prehemodialysis and posthemodialysis blood HCV levels and HCV escape to spent dialysate. Because heparin has an inhibitory effect on the reverse-transcription polymerase chain reaction (RT-PCR) assay, a serine protease inhibitor (nafamostat mesilate) was used as the anticoagulant for hemodialysis. High-flux polysulfone membrane dialyzers were used; dialyzer reuse was not performed. Multicyclic RT-PCR was performed for the quantitative detection of HCV. To elucidate HCV escape to spent dialysate, a portion of total spent dialysate was continuously extracted in a sterile fashion using a minutely adjusted syringe pump. No HCV extravasation to spent dialysate was found, although HCV copy numbers were reduced to a statistically significant level in postdialysis blood compared with predialysis levels (P: < 0.05; n = 20). The need to establish standards for risk management in dialysis centers is evident. The data obtained in this study strongly suggest that to minimize the risk for HCV transmission, lower transmembrane pressure (TMP) should be used in the hemodialysis of HCV-positive patients, with fresh polysulfone dialyzers and dialysis settings of 180 to 250 mL/min for blood flow, 500 mL/min for dialysate flow, and less than 18.72 mm Hg for TMP.

Blood↗
PubMed2001

Mesangial IgA2 deposits and lectin pathway-mediated complement activation in IgA glomerulonephritis.

Three pathways are recognized in complement activation. The aim of our study is to elucidate immunohistologically which complement pathway is associated with complement activation in immunoglobulin A (IgA) glomerulonephritis (GN) and which IgA subclass is related to complement activation. Immunohistological staining was performed on renal biopsy specimens obtained from 36 patients with IgA GN, 10 patients with systemic lupus erythematosus (SLE), and 16 patients with other GNs using polyclonal antibodies of IgG, IgA, IgM, C1q, C3c, and C4 and monoclonal antibodies of IgA1, IgA2, mannose-binding lectin (MBL), and MBL-associated serine protease-1 (MASP-1). Mesangial deposits of both IgA1 and IgA2 were found in 19 of 36 patients with IgA GN. Mesangial deposits of C3c, C4, MBL, and MASP-1 also were detected in these 19 patients, and IgA2, MBL, and MASP-1 deposits were colocalized in the mesangium in these patients. The remaining 17 patients showed mesangial deposits of IgA1 alone. Twelve of these 17 patients showed mesangial deposits of C3c without C4, MBL, or MASP-1. No deposition of C1q was evident in patients with IgA GN. Three of 10 patients with SLE showed glomerular deposition of MBL and MASP-1 without glomerular deposition of IgA2. None of the patients with other GNs showed glomerular deposition of IgA1, IgA2, MBL, or MASP-1. There was no correlation in clinical or pathological indicators between IgA2-positive and IgA2-negative patients with IgA GN. In conclusion, alternative pathway-involved complement activation is associated with mesangial deposits of IgA1 alone in patients with IgA GN. In those with mesangial deposits of both IgA1 and IgA2, both the alternative and lectin pathways are involved in complement activation. We first report that mesangial deposits of IgA2 may activate the lectin pathway in patients with IgA GN.

Adolescent↗
PubMed2001

Polymorphisms of the insulin gene among Japanese subjects.

We have sequenced the insulin gene in 72 unrelated Japanese subjects (52 with type 2 diabetes mellitus and 20 with normal glucose tolerance). We identified 6 mutations and all were found at a low frequency (1% to 4%). Three mutations were new. These included a C-to-G substitution in the promoter region, a G-to-A substitution in codon-2 resulting in an Ala-to-Thr replacement in amino acid -2 of the signal peptide, and a G-to-A substitution in intron 2. We have no evidence that any of the mutations that we found are the cause of diabetes. Thus, mutations in the insulin gene do not appear to be an important genetic factor contributing to the development of diabetes in this population.

Adult↗
PubMed2001

The effects of fatty acyl CoA esters on the formation of prostaglandin and arachidonoyl-CoA formed from arachidonic acid in rabbit kidney medulla microsomes.

Under physiological conditions, small amounts of free arachidonic acid (AA) are released from membrane phospholipids, and cyclooxygenase (COX) and acyl CoA synthetase (ACS) competitively act on this fatty acid to form prostaglandins (PGs) and arachidonoyl-CoA (AA-CoA). We have previously shown that palmitoyl-CoA (PA-CoA) shifts AA away from the COX pathway into the ACS pathway in rabbit kidney medulla at a low concentration of AA (5 microM, close to the physiological concentration of substrate). In the present study, we investigated the effects of stearoyl (SA)-, oleoyl (OA)- and linoleoyl (LA)- CoAs on the formation of PG and AA-CoA from 5microM AA in rabbit kidney medulla microsomes. The kidney medulla microsomes were incubated with 5microM [(14)C]-AA in 0.1 M-Tris/HCl buffer (pH 8.0) containing cofactors of COX (reduced glutathione and hydroquinone) and cofactors of ACS (ATP, MgCl(2)and CoA). After incubation, PG (as total PGs), AA-CoA and residual AA were separated by selective extraction using petroleum ether and ethyl acetate. SA- and OA-CoAs increased AA-CoA formation with a reduction of PG formation, as well as PA-CoA. On the other hand, LA-CoA decreased formation of both PG and AA-CoA. These results suggest that fatty acyl CoA esters can be regulators of PG and AA-CoA formation in kidney medulla under physiological conditions.

Acyl Coenzyme A↗
PubMed2001

PGl2 analogue mitigates the progression rate of renal dysfunction improving renal blood flow without glomerular hyperfiltration in patients with chronic renal insufficiency.

Renal blood flow decreases with the progression of chronic glomerulonephritis (CGN). This disease induces medullary ischemia and further renal dysfunction in patients with chronic renal insufficiency (CRI). Prostacyclin (PGI2), with its vasodilative action, increases renal blood flow (RBF) without increasing glomerular filtration rate (GFR). We therefore examined the possibility that PGI2 would mitigate the progression of renal dysfunction by increasing RBF in patients with CRI. Sixteen patients with progressive renal insufficiency (serum creatinine: 2.14+/-0.89 mg/dl) due to CGN were prospectively chosen for this study. The blood pressure was already under control using calcium channel blockers before and during this study in nine hypertensive patients. In the first 6 months the patients received a low-protein (0.6 g/kg/day) and low-salt (5.0 g/day) diet. In the next 6 months they received 60 microg/day of PGI2 analogue (Beraprost sodium) orally. GFR was determined by 24-hour creatinine clearance, and effective renal plasma flow (ERPF) was determined by 99mTc-MAG3 scintigraphy. Glomerular capillary pressure, the resistance ratio of afferent and efferent arterioles (R(A)/R(E)), and the other hemodynamic parameters from Gomez's estimation equation were determined at the start of this study, just before the administration of Beraprost and at the end of the study. The levels of GFR and ERPF were 34.6+/-12.4 and 140.6+/-52.1 ml/min at the start of this study respectively, and decreased to 28.0+/- 12.0 and 115.6+/-45.3 ml/min after the first 6 months without Beraprost. The levels of GFR and ERPF stayed at 28.1+/-15.7 and 119.2+/-57.6 ml/min after the next 6 months with Beraprost in the same patients. R(A)/R(E) increased in the first 6 months from 7.9+/-3.6 to 10.8+/-8.6, but remained constant during 6 months of Beraprost administration, at 10.5+/-8.0. These data indicate that PGI2 analogue diminishes the vascular resistance of glomerular afferent and efferent arterioles regulating the decrease of renal blood flow without glomerular hyperfiltration, thus mitigating the progression rate of renal dysfunction.

Creatinine↗
PubMed2001

Epidermal growth factor induces expression of decay-accelerating factor in human colonic cancer cells via the mitogen-activated protein kinase pathway.

The expression of decay-accelerating factor (DAF), a complement regulatory protein, is enhanced in colorectal cancer. In this study, to elucidate mechanisms for enhanced DAF expression, we studied the effects of growth factors on DAF expression in HT-29 human colonic cancer cells. Cells were treated with epidermal growth factor (EGF), insulin-like growth factor-I, platelet-derived growth factor, and transforming growth factor-beta. DAF protein expression and mRNA expression were determined with enzyme immunoassay and Northern blot analysis. The signaling pathways that target DAF expression in response to growth factor stimulation were characterized by using various inhibitors of the signal transduction pathway. EGF induced significant increases in DAF protein and mRNA expression in HT-29 cells; the other growth factors had a weak effect or no effect. The EGF-induced DAF expression was inhibited by mitogen-activated protein (MAP) kinase kinase inhibitor PD 98059 but not by phosphatidylinositol-3 kinase inhibitor, phospholipase Cgamma inhibitor, or protein kinase C inhibitor. When we analyzed the phosphorylation state of the MAP kinase by immunoblot analysis, phosphorylated p44/p42 MAP kinase was detected in EGF-stimulated HT-29 cells, and the addition of PD 98059 abrogated the phosphorylation. These results indicate that EGF regulates DAF expression in HT-29 cells via the signaling pathway that depends on the activation of MAP kinase.

Blotting, Northern↗
PubMed2001

Relationship between circulating high density lipoprotein concentrations and interleukin-6 release during abdominal operations.

OBJECTIVE: To investigate whether circulating high density lipoprotein (HDL) concentrations influence inflammatory cytokine release during abdominal operations. SETTING: University Hospital, Japan. PATIENTS: 30 patients who underwent curative operations for gastric cancer. MAIN OUTCOME MEASURES: Serum HDL and cytokine concentrations were measured preoperatively, and portal and systemic blood samples were taken for the analysis of cytokine and endotoxin concentrations during operations. RESULTS: Portal blood interleukin-6 (IL-6) values of patients with low serum HDL concentrations (n = 6) (< 0.9 mmol/L) were significantly (p < 0.01) higher than those in patients with normal or high HDL concentrations (n = 24) (> or = 0.9 mmol/L) (80.63 (74.62) pg/ml (mean (SD)) compared with 10.25 (9.61) pg/ml.). Moreover, an inverse correlation (r = -0.43, p < 0.05) was found between portal blood IL-6 concentrations and circulating HDL concentrations. CONCLUSIONS: We suggest that serum HDL concentrations influence IL-6 release in response to abdominal operations. Circulating HDL particles may reduce endotoxin-induced IL-6 release in humans.

Aged↗
PubMed2001

Angiotensin converting enzyme protects acetylcholine-induced relaxation from its attenuation by formyl-methionyl-leucyl-phenylalanine in rat aorta.

OBJECTIVE: A chemotactic tripeptide formyl-methionyl-leucyl-phenylalanine (fMLP) attenuated acetylcholine (ACh)-induced relaxation. Because angiotensin converting enzyme (ACE), which inactivates fMLP, is rich in vascular endothelial cells, we examined whether endothelial cell ACE inhibits the attenuating effect of fMLP on ACh-induced relaxation. DESIGN AND METHODS: ACh-induced relaxation was evaluated in aortic rings from 9-week-old Sprague-Dawley rats. We examined the effects of ACE, the ACE inhibitor captopril and/or fMLP on ACh-induced relaxation in aortas from rats with or without dexamethasone treatment, which enhances ACE activity. RESULTS: Pre-treatment with ACE did not alter ACh-induced relaxation in control aortas but abolished the inhibitory effect of fMLP on ACh-induced relaxation [maximal relaxation (Emax): 95.4 +/- 1.2 versus 75.5 +/- 1.9%, P < 0.05]. Conversely, captopril enhanced the attenuation of ACh-induced relaxation by fMLP (Emax: 62.5 +/- 3.3 versus 74.0 +/- 2.2%, P < 0.05), although captopril did not affect ACh-induced relaxation in control aortas. In addition, fMLP did not attenuate ACh-induced relaxation in aortas from dexamethasone-treated rats (Emax: 89.7 +/- 3.7 versus 85.2 +/- 3.8%, NS), which enhanced ACE activity of aortas (3.37 +/- 0.25 versus 2.70 +/- 0.20 IU/mg protein, P < 0.05). CONCLUSION: Endothelial-cell ACE attenuates the effect of fMLP on ACh-induced relaxation, possibly by its cleavage.

Acetylcholine↗
PubMed2001

Hypoxic induction of adrenomedullin in cultured human umbilical vein endothelial cells.

OBJECTIVES: The current study evaluated the hypoxic induction of adrenomedullin gene expression and secretion, and its mechanism in cultured human umbilical vein endothelial cells (HUVEC). METHODS: HUVEC were exposed to hypoxia or normoxia as controls for 1 to 24 h. Using Northern blot analysis and a radioimmunoassay, we evaluated adrenomedullin expression in HUVEC. The transcriptional component of adrenomedullin gene regulation was assessed by nuclear run-off experiments, and adrenomedullin mRNA half-life was measured by actinomycin D experiments. RESULTS: We found that hypoxic conditions (1-3% oxygen) significantly increased adrenomedullin mRNA and protein in HUVEC. This increase was inversely proportional to oxygen tension and was reversible upon re-exposure to a 21% oxygen environment Nuclear run-off experiments revealed the enhanced transcriptional rate of adrenomedullin gene. Next, actinomycin D experiments revealed the enhanced adrenomedullin mRNA stability. CONCLUSIONS: These results indicate that hypoxia increases adrenomedullin gene expression and secretion in HUVEC by transcriptional and post-transcriptional mechanisms. Hypoxic induction of adrenomedullin may play a pathophysiological role in the vascular systems.

Adrenomedullin↗
PubMed2001

Effects of ouabain on the growth and DNA synthesis of PC12 cells.

We investigated the effects of ouabain and serum from salt-loaded Dahl salt-sensitive (S) rats, which contain abundant ouabain-like compounds, on the growth and DNA synthesis of rat pheochromocytoma PC12 cells. Ouabain decreased the growth of PC12 cells, as evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, in a concentration-dependent fashion. A moderate concentration (10(-7) M) of ouabain increased DNA synthesis, as measured by 5-bromo-2'-deoxyuridine incorporation, and induced transcription of the proto-oncogenes c-myc and c-fos. Serum from salt-loaded Dahl S rats also enhanced DNA synthesis, but serum from Dahl salt-resistant rats did not. Thus ouabain-like compounds may modify the growth or differentiation of neural tissues. This effect may contribute to the development of salt-induced hypertension in Dahl S rats.

Animals↗
PubMed2001

Treatment of ischial pressure ulcers with a posteromedial thigh fasciocutaneous flap.

This study describes the use of the posteromedial thigh fasciocutaneous flap for the treatment of ischial pressure sores. The authors prefer this flap because it is the fasciocutaneous flap nearest to the ischial region, it is easy to raise, and it causes no donor-site morbidity. In this study, 11 ischial pressure sores in 10 paraplegic patients were closed using the posteromedial thigh fasciocutaneous flaps. All flaps survived, although two caused distal necrosis; after these same two flaps were readvanced, they survived. After an average follow-up time of 77 months, seven of the 10 patients have had no recurrence of ulcers. This fasciocutaneous flap was previously described by Wang et al. However, this study revealed that the arrangement of the vascular pedicle was different from that described by Wang et al. To reveal the vascular supply of this flap, anatomic dissections were conducted. The source of circulation to this flap was the suprafascial vascular plexus, in addition to the musculocutaneous perforator. The dominant pedicle was the musculocutaneous perforator from either the adductor magnus muscle or the gracilis muscle. The key to safe elevation of this flap was the accurate outlining of the skin island directly over the vascular pedicle and the preservation of the proximal fascial continuity. Of the 11 flaps, two viability problems occurred. These partial flap losses resulted from the failure to properly include the perforator. It is the authors' conclusion that the width of the flap should be greater than 5 cm. In addition, it is safe to make a flap within a 1:3 base-to-length ratio in a fatty, diabetic patient. This posteromedial thigh fasciocutaneous flap was found to be a valuable alternative for reconstruction of primary or recurrent ischial pressure ulcers.

Adult↗
PubMed2001

Inactivating mutations of calcium-sensing receptor results in parathyroid lipohyperplasia.

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disease characterized by mild hypercalcemia, an inappropriately high parathyroid hormone level, and absence of hypercalciuria. Heterozygous inactivating mutations of calcium-sensing receptor (CaSR) are found in about two thirds of patients with FHH. Histologic examination of parathyroid glands in FHH is reported to show normal histology or chief cell hyperplasia. Thus, histologic features of the parathyroid glands in FHH vary, and there is no clear histologic criterion that indicates FHH. The authors have encountered three hypercalcemic patients with characteristic histologic features of enlarged parathyroid glands. Clusters of parenchymal cells were mixed with fat cells, and the area of fat cells was 33% to 49% of the total area. These features are similar to those described as parathyroid lipohyperplasia. Postoperative evaluation showed that fractional excretion of calcium was low in these patients. Direct sequencing of the polymerase chain reaction product showed that the first patient was heterozygous for an already reported inactivating mutation of CaSR (P55L). The second patient was also heterozygous for a novel inactivating mutation (R220W). The third was homozygous for an inactivating mutation (Q27R). These results indicate that histologic features of parathyroid lipohyperplasia suggest the presence of inactivating mutations of CaSR.

Adipose Tissue↗