Rapid loss of insulin secretion in a patient with fulminant type 1 diabetes mellitus and carbamazepine hypersensitivity syndrome.
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Aged↗
Biomedical subjects
T Fujita
Publications and source records attributed to T Fujita.
Redox-sensitive regulation of lox-1 gene expression in vascular endothelium.
Oxidative stress has been implicated in atherosclerosis and its underlying conditions. LOX-1 is a novel endothelial receptor for oxidized low-density lipoprotein which might mediate endothelial dysfunction and subsequent atherogenesis. In the present study, we examined LOX-1 gene regulation by oxidative stress. First, superoxide anions generated by hypoxanthine and xanthine oxidase as well as hydrogen peroxide increased LOX-1 mRNA expression in cultured aortic endothelial cells. Homocysteine, an atherogenic substance believed to exert its effects through oxidative stress, enhanced endothelial LOX-1 gene expression, which was suppressed by N-acetylcysteine. Second, rats receiving angiotensin II for 10 days manifested hypertension and LOX-1 upregulation in aortic endothelium via AT1 receptor. Tempo, a superoxide dismutase mimetic, alleviated LOX-1 augmentation induced by angiotensin II. These results indicated redox-sensitive upregulation of LOX-1 mRNA in both in vitro and in vivo systems, suggesting its potential role in atherosclerosis.
Angiotensin II↗
Closing-opening wedge osteotomy to correct angular kyphotic deformity by a single posterior approach.
STUDY DESIGN: Seven patients with angular kyphotic deformity of the thoracic or thoracolumbar spine were treated by closing-opening wedge osteotomy using a single posterior approach. OBJECTIVES: To examine the safety and efficacy of closing-opening wedge osteotomy for angular kyphosis. SUMMARY OF BACKGROUND DATA: Correction osteotomy of severe kyphosis is a challenging operation. A two-stage operation has been commonly used: anterior release and decompression followed by posterior correction and fusion. METHODS: Seven patients with angular kyphosis were treated. The apex level of kyphosis was T5 in one patient, T11 in one, and T12 in five. There was old fracture in five patients, congenital deformity in one, and neurofibromatosis in one. The first 30-35 degrees of kyphosis are corrected using the closing wedge technique with the hinge of the anterior longitudinal ligament after veretebrectomy and circumspinal decompression of the spinal cord. Then the hinge is moved posteriorly to the spinal cord and the remainder of the requisit angle of osteotomy is corrected using the opening-wedge technique (closing-opening wedge osteotomy). Spinal curvature is stabilized using posterior instrumentation and graft. RESULTS: Localized kyphosis was reduced from an average of 67 degrees to 18 degrees at 2.2 to 7.5 years' follow-up. Sagittal alignment from T1 to the sacrum became more physiologic than before. There were no neurologic complications. Bony fusion was achieved in all patients, and there was no correction loss. CONCLUSIONS: Satisfactory correction is safely performed by closing-opening wedge osteotomy with a direct visualization of the circumferentially decompressed spinal cord. Although the performance is technically laborious, it offers good correction without jeopardizing the integrity of the spinal cord.
Adult↗
Characterization of multiple Chinese hamster carbonyl reductases.
Carbonyl reductase (CR) is an enzyme which can catalyze the oxidoreduction of various carbonyl compounds in the presence of NAD(P)H. With the PCR method, using primers carrying the conserved nucleotide sequence among mammalian CRs, we isolated three different cDNAs (CHCR1, CHCR2 and CHCR3) which encode a unique carbonyl reductase from the Chinese hamster. The PCR products of CHCR1 and CHCR2 were clearly isolated with Bpu1102I, BspEI and XmaI restriction enzymes. The nucleotide-sequence of CHCR3 was completely different from those of CHCR1 and CHCR2. The predicted double-wound betaalphabetaalpha-structures of the CHCRs suggests the presence of a typical NADP(+)-binding motif and is similar to the corresponding region of 3alpha,20beta-hydroxysteroid dehydrogenase and mouse lung tetrameric carbonyl reductase. The deduced amino acid sequence of CHCR1 showed a high homology to CHCR2 (>96%) and the other mammalian CRs (>81%). However, CHCR3 showed a high homology to human CBR3 (>86%) and a relatively lower homology to the other CHCRs (<76%). Bacterial recombinant CHCRs showed typical carbonyl reductase activities towards 4-benzoylpyridine, 4-nitrobenzaldehyde and pyridine 4-carboxyaldehyde. These three CRs showed not only 3-keto reductase of steroids, but also 20-keto reductase. However, these CRs did not show any activity of 17-keto reductase activity. Both CHCR1 and CHCR2 have prostaglandin 9-keto reductase and 15-hydroxyprostaglandin dehydrogenase activities towards PGE(2) and PGF(2alpha) from the analyses of enzymatic reaction products. The results of Western blotting and RT-PCR suggest these CHCRs have a tissue-dependent-distribution in the Chinese hamster.
Alcohol Oxidoreductases↗
Phosphate provides an extracellular signal that drives nuclear export of Runx2/Cbfa1 in bone cells.
Inorganic phosphate (Pi) supplement is generally used to accelerate mineralization of cultured bone cells but the mechanism of action is totally unknown. How the action is related with the transactivation of Runx2/Cbfa1,a master gene product of bone formation,was examined. Clonal bone cells (osteoblastic MC3T3-E1, chondrocytic ATDC5 and osteocytic MLO-Y4) on preculture in ascorbate-containing medium constantly expressed and accumulated Cbfa1 in the nuclei, and subsequent increase of Pi concentration to 3 or 10 mM was found to invariably induce nuclear export (not import) of Cbfa1 which was completed in a few hours. In addition, Pi was found to lower the expression of osteocalcin. Leptomycin B completely inhibited Pi-induced nuclear export, suggesting that CRM1/exportin 1 is involved in Pi-induced nuclear export. The result suggests that bone cells are equipped with a novel Pi sensing mechanism which is functionally linked to a nuclear export system of Cbfa1.
3T3 Cells↗
Smad-mediated transcription is required for transforming growth factor-beta 1-induced p57(Kip2) proteolysis in osteoblastic cells.
Cyclin-dependent kinase inhibitory proteins (CKIs) are negative regulators of the cell cycle. Of all CKIs, only p57(Kip2) plays an essential role(s) that other CKIs cannot compensate for in embryonic development. Recently, we found that p57(Kip2) is degraded through the ubiquitin-proteasome pathway in osteoblastic cells stimulated to proliferation by transforming growth factor (TGF)-beta1 (Urano, T., Yashiroda, H., Muraoka, M., Tanaka, K., Hosoi, T., Inoue, S., Ouchi, Y., and Toyoshima, H. (1999) J. Biol. Chem. 274, 12197-12200). We report here that TGF-beta1-induced p57(Kip2) proteolysis is mediated through transcription by the Smad pathway. When the constitutively active form of the TGF-beta type I receptor ALK-5(TD) was ectopically expressed in osteoblastic cells, p57(Kip2) that had been accumulated by serum starvation causing the cell-cycle arrest was rapidly degraded in a manner analogous to TGF-beta1 stimulation. Moreover, Smad2 or Smad3 with Smad4 enhanced the proteolytic pathway of p57(Kip2). The degradation of p57(Kip2) evoked by TGF-beta1 was blocked by forced expression of an inhibitory Smad called Smad7 or by the addition of actinomycin D or alpha-amanitin. These results indicate that accelerated degradation of p57(Kip2) by TGF-beta1/Smad signaling is mediated through a newly synthesized factor(s) that modifies p57(Kip2) or the ubiquitin-proteasome pathway.
Animals↗
Enhanced absorption of insulin and (Asu(1,7))eel-calcitonin using novel azopolymer-coated pellets for colon-specific drug delivery.
The objective of this study was to estimate colon-specific delivery of insulin and (Asu(1,7))eel-calcitonin using novel azopolymer-coated pellets. In vitro drug-release experiments from the azopolymer-coated pellets containing fluorescein isothiocyanate dextran (MW 4400; FD-4) were carried out by the Japanese Pharmacopoeia (J.P.) XIII rotating basket method with some slight modifications. Little release of FD-4 from the pellets was observed in phosphate buffered saline. However, the release of FD-4 was markedly increased in the presence of rat cecal contents. The intestinal absorption of insulin and (Asu(1,7))eel-calcitonin after oral administration of the azopolymer-coated pellets containing these peptides with camostat mesilate was evaluated by measuring the hypoglycemic and hypocalcemic effects, respectively. A slight decrease in plasma glucose levels was observed following the oral administration of these pellets containing 12.5 IU of insulin compared with the same dose of insulin solution. Camostat mesilate, a protease inhibitor that is incorporated with insulin in these pellets, further decreased the plasma glucose levels in a dose-dependent manner. Similar results were also obtained with the oral administration of pellets containing (Asu(1,7))eel-calcitonin. These findings suggest that azopolymer-coated pellets may be useful carriers for the colon-specific delivery of peptides including insulin and (Asu(1,7))eel-calcitonin.
Administration, Oral↗
Quantitative structure-activity studies of insect growth regulators: XVIII. Effects of substituents on the aromatic moiety of dibenzoylhydrazines on larvicidal activity against the Colorado potato beetle Leptinotarsa decemlineata.
Larvicidal activity against the Colorado potato beetle Leptinotarsa decemlineata (Say) was measured for a series of N-tert-butyl-dibenzoylhydrazines having various substituents on the benzoyl (A-ring) moiety nearer to the tert-butyl group, with the other benzoyl (B-ring) moiety being unsubstituted. The effects of these substituent on the larvicidal activity were analyzed using classical quantitative structure-activity relationship (QSAR) procedures. The effects of substituents on the A-ring moiety on larvicidal activity were entirely different from those against the lepidopteran rice stem borer Chilo suppressalis (Walker) previously reported. Position-specific steric and hydrophobic effects, as well as certain substitution patterns, were likely to participate in modifying the larvicidal activity. The activity of para-substituted compounds was generally lower than that of un-, ortho- and meta-substituted compounds. Most multi-substituted compounds showed an activity equivalent to or lower than that of the unsubstituted compound. Among 46 compounds tested, the 2-sec-butoxy analogue was most potent against L decemlineata, although this compound had previously been shown to be only weakly active against C suppressalis.
Animals↗
Cryoprecipitate of patients with cryoglobulinemic glomerulonephritis contains molecules of the lectin complement pathway.
Serological and histological studies were carried out to explore the role of the lectin complement pathway in the pathogenesis of cryoglobulinemic glomerulonephritis. Sixteen patients with mixed cryoglobulinemia type II with glomerulonephritis (GN) were enrolled. All cases had hepatitis C virus (HCV) infection. The serum concentration of mannose-binding lectin (MBL) was significantly higher in the GN patients than in the normal controls according to ELISA (P < 0.01). IgG, IgM, C1q, C4d, HCV envelope antigen, MBL, and MBL-associated serine protease-1 (MASP-1) could be visualized in the cryoprecipitate of the 16 patients by Dot blot assay. Renal biopsy specimens obtained from 3 patients were examined by immunohistochemistry, and the glomeruli strongly stained for IgG, IgM, MBL, MASP-1, C4d, C3c, and C3d in a fringe-like pattern. The pattern of HCV constituent deposition was partially fringe-like. The complement profiles of the 16 cases were distinctive; briefly, the serum levels of C1q, C2, and C3 were reduced, although the levels of circulating regulatory proteins (C1-inhibitor, factor H, and factor I) were in the normal range. The serum C4 level was significantly reduced. These results indicate that immune complex formation involves molecules of the lectin pathway and leads to organ damage in cryoglobulinemic glomerulonephritis.
Adolescent↗
Tetrahydrobiopterin attenuates modulation of platelet 12-lipoxygenase and cyclooxygenase activities by nitric oxide.
Endothelial cells secrete large amounts of 5,6,7,8-tetrahydrobiopterin (BH(4)) in septic conditions. BH(4) is a cofactor for nitric oxide (NO) synthase and an essential regulator of its activity. We recently showed that NO can be a modulator of both platelet 12-lipoxygenase and cyclooxygenase activities. In the present study, we investigated the effect of BH(4) on the activities of 12-lipoxygenase and cyclooxygenase in rabbit platelets. The influence of BH(4) on NO-induced modulation of these enzyme activities was investigated. Exogenous BH(4) did not affect platelet 12-lipoxygenase and cyclooxygenase activities. The modulatory effects of NO on the two enzymatic pathways were reversed by addition of BH(4) but not by reduced glutathione. These results suggest that exogenous BH(4) is not essential for NO synthase activity of platelets, but that it is an important regulator of the action of NO released from other sources on platelet 12-lipoxygenase and cyclooxygenase activities.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
Cut-off values determined for vertebral fracture by peripheral quantitative computed tomography in Japanese women.
In spite of the benefits of bone mass measurement by dual-energy X-ray absorptiometry (DXA), the use of DXA has limitations. It is unable to assess a true bone density, and cannot discriminate between the trabecular and cortical bone compartments. Ultradistal radius bone density was measured using peripheral quantitative computed tomography (pQCT) to determine reference values for total bone density (BD), trabecular bone density (TBD), polar strength strain index (pSSI), total bone mineral content (BC), trabecular bone mineral content (TBC), cortical bone density (CBD), cortical bone mineral content (CBC) and polar cross-sectional moment of inertia (pCSMI) in the Japanese female population, and to ascertain the cut-off values of the measured indicators that could most efficiently discriminate osteoporotic subjects with vertebral fractures. A total of 5266 healthy Japanese women aged 20-89 years were included in this study to determine Japanese reference values. Additionally, 621 who had undergone radiographic examination of the thoracic and lumbar spine at the time of pQCT measurement were selected to determine the cut-off values of BD, TBD, pSSI and other indicators for vertebral fractures. All the healthy subjects were divided into 5 year age groups. The BD showed nonsignificant changes from the 20-24 year age group to the 45-49 year age group, and fell significantly thereafter. The TBD maintained a plateau until the 40-44 year group, which corresponds to the young adult mean (YAM) values of the lumbar spine, femoral neck and radius BMDs measured using DXA. The TBD decreased significantly thereafter. The pSSI did not change significantly from the 20-24 year age group to the 45-49 year age group, and decreased slightly in the 50-54 year age group and markedly after 55-59 years. The cut-off values for the discrimination of vertebral fractures were obtained by the calculation of sensitivities, specificities and the area under the curves obtained using age-adjusted receiver operating characteristics (ROC) analysis. Odds ratios and 95% confidence limits (CL) were calculated using age-adjusted logistic analysis. The cut-off values for vertebral fractures, the area under the ROC curves (AUC) and odds ratios were 270.1 mg/cm3 (-2.2 SD, 66.6% of YAM), 0.689+/-0.025, 2.10 (1.63, 2.70) for BD, 104.8 mg/cm3 (-2.2 SD, 53.5% of YAM), 0.699+/-0.023, 2.17 (1.69, 2.77) for TBD and 192.8 mm3 (-1.9 SD, 59.8% of YAM), 0.631+/-0.028, 1.72 (1.34, 2.21) for pSSI, respectively. These findings suggest that ultradistal radius BMD measured using pQCT can be used to discriminate women with vertebral fractures.
Adult↗
Oral glucocorticoid-induced fall in cortical bone volume and density in postmenopausal asthmatic patients.
Despite a deepening understanding of the influence of glucocorticoids (GC) on trabecular bone, little is known about GC-induced cortical bone loss. To elucidate the mechanism of GC-induced loss of cortical bone strength with particular reference to cortical bone loss, changes in cortical density, relative cortical volume, and the Strength Strain Index (SSI) based on biomechanical analyses of the geographic distribution of cortical bone material were measured. These parameters were compared, using peripheral quantitative computed tomography (pQCT), among the following age-matched groups: 68 postmenopausal asthmatic patients receiving high-dose oral GC in addition to inhaled GC (oral GC group), 68 postmenopausal asthmatic patients receiving only inhaled GC (inhaled GC group) and 69 postmenopausal controls without asthma or GC therapy (control group). Cortical bone mineral density (BMD) was measured, relative cortical volume was obtained by dividing the cortical area by the total bone area using pQCT (Stratec XCT960), and the Strength Strain Index (SSI) was calculated in the radius based on the density distribution around the axis. Spinal fracture was assessed on lateral radiographs. The number of vertebral fractures per patient correlated highly with cortical BMD, relative cortical volume and SSI values at the radius. The number of vertebral fractures per patient and the number of patients with fracture were similar between the control and inhaled GC group, both being significantly lower than those in the oral GC group. Total BMD, trabecular BMD, cortical BMD, relative cortical volume and SSI were similar between the first two, being significantly higher than in the last group. The slopes of cortical volume-density relationship, however, were identical among the three groups, indicating the persistence of cortical bone remodeling and a similar degree of calcification regardless of GC administration.
Administration, Inhalation↗
Reduced albumin reabsorption in the proximal tubule of early-stage diabetic rats.
The aim of this study is to investigate the role of the proximal tubule in microalbuminuria in the early stage of diabetic nephropathy. Diabetes was induced in male Sprague-Dawley rats by an injection of streptozotocin (50 mg/kg, i.v.). After 2 weeks, albumin delivery in the proximal tubule was measured using micropuncture and the endocytosis process of FITC-labeled albumin was evaluated with immunoelectron microscopy. Albumin was significantly reabsorbed in the proximal convoluted tubule (PCT) of controls (0.39+/-0.05 ng/min at early PCT to 0.17+/-0.08 at late PCT, P<0.05), whereas albumin reabsorption was inhibited in diabetic rats (0.27+/-0.05 to 0.21+/-0.08). Immunogold study revealed that FITC-albumin was significantly less reabsorbed in endosomes and lysosomes of S1 segments in diabetic rats than in controls (endosome: 1.20+/-0.10 vs 2.16+/-0.15 microm-1, P<0.0001; lysosome: 0.26+/-0.03 vs 0.83+/-0.07, P<0.0001). The expression of megalin, an endocytosis receptor, was decreased at the apical membrane of PCT in diabetic rats. The lipid peroxidation production in the proximal tubule was significantly increased in diabetic rats. In conclusion, albuminuria in early-stage diabetic rats can be partly explained by a decreased albumin endocytosis with reduced megalin expression and with increased lipid peroxidation in the proximal tubule.
Albumins↗
A case of renal involvement in persistent immune activation caused by chlamydial salpingitis.
A 24-year-old woman presented with renal insufficiency, macrohematuria, and mild urinary protein. Polyclonal hypergamma-globulinemia, thrombocytosis, increased concentration of serum, and urinary interleukin (IL)-6 all indicated persistent immune activation caused by a Chlamydia trachomatis infection of the fallopian tube. Gynecological treatment with levofloxacin was effective both for the renal symptoms and other immunological parameters. First and second renal biopsy specimens showed an immune-complex glomerulopathy with extensive interstitial infiltration of many types of inflammatory cells, including plasma cells. Thus, we conclude that chlamydial salpingitis must be considered as one causative disease factor for renal involvement by means of its persistent immune activation effects.
Adult↗
Primary intestinal lymphangiectasia successfully treated with octreotide.
A 21-year-old man with diarrhea and edema was admitted to our hospital and diagnosed with protein-losing enteropathy caused by primary intestinal lymphangiectasia. He was placed, in turn, on a low-fat diet, an elemental diet, and, subsequently, fasting therapy with total parenteral nutrition (TPN) support. However, his symptoms were not relieved, but, rather were exacerbated. On the 45th day of hospitalization, octreotide therapy was initiated. After 2 weeks of treatment, his clinical symptoms, as well as hypoproteinemia and hypoalbuminemia, gradually became alleviated. The improvement was confirmed in terms of scintigraphy, endoscopy, and histology of the duodenum. The patient remained healthy until 6 months after the commencement of octreotide treatment, when he discontinued octreotide at his own discretion, at which point the symptoms recurred. Resumption of the drug, however, again brought about remission, which has continued until the present, March 2000. Thus, octreotide therapy is one modality which may be useful for refractory primary intestinal lymphangiectasia.
Adult↗
Analgesic effect of etidronate on degenerative joint disease.
In the present study, 80 patients with degenerative joint disease, spondylosis deformans, and/or osteoarthritis of the knee with back or joint pain, especially on movement and strain, were randomly divided into four groups. Group A received no etidronate, while groups B, C and D received 66, 133 and 200 mg/day etidronate, respectively, for 12 months. Every 3 months, after evaluating subjective pain on a visual rating scale (VRS), skin impedance was measured with subjects in a quiet sitting position and with the application of various strains on the spine and knee, including standing up from quiet sitting on a chair, bending forward to flex the spine, squatting to flex the knee, walking 20 paces on a flat floor, ascending 10 stair steps and descending 10 stair steps. A dose related improvement of subjective pain on the VRS with a parallel decrease in the percentage fall in skin impedance was noted. The intra-individual coefficients of variation (CV) of L1-L4 bone mineral density (BMD) on dual-energy X-ray absorptiometry were calculated as a possible index for spondylotic changes before and after treatment as an indication of spondylotic deformity, because no established method is yet available to evaluate such changes objectively. A dose-related decrease in CV of BMD was also noted, parallel to the analgesic effect.
Aged↗
Global assessment of risk factors for osteoporosis.
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Global Health↗
Fall of skin impedance and bone and joint pain.
Pain is a complex neurophysiological and psychological process associated with various electrodermal phenomena, including Galvanic skin response, a fall of resistance to Galvanic current. Because skin impedance, an alternative current counterpart of direct current resistance, is readily measured and is probably more sensitive and stable in reflecting the state of the skin, the relationship between changes in pain and skin impedance was evaluted in the present study. Baseline skin impedance was stable and reproducible within a short time of less than 1 h and on consecutive days with a coefficient of variation of 1%-4%, but it may vary more widely over a longer period of 1 year. Baseline skin impedance gradually rose with advancing age, and females tended to show higher values than males. A highly significant correlation was noted between the percentage fall in skin impedance in response to strain on the joint, such as standing, bending, squatting, walking on a flat floor, and ascending and descending stairs, and pain scores obtained by a visual rating scale according to the Spearman's rank correlation coefficient test. Measurement of the fall in skin impedance may be a useful index of pain-associated somatic changes for a better understanding of the overall manifestations of pain as a step toward to an objective evalution of pain.
Age Factors↗