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J Wada

Publications and source records attributed to J Wada.

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

Identification of a renal-specific oxido-reductase in newborn diabetic mice.

Aldose reductase (ALR2), a NADPH-dependent aldo-keto reductase (AKR), is widely distributed in mammalian tissues and has been implicated in complications of diabetes, including diabetic nephropathy. To identify a renal-specific reductase belonging to the AKR family, representational difference analyses of cDNA from diabetic mouse kidney were performed. A full-length cDNA with an ORF of 855 nt and yielding a approximately 1.5-kb mRNA transcript was isolated from a mouse kidney library. Human and rat homologues also were isolated, and they had approximately 91% and approximately 97% amino acid identity with mouse protein. In vitro translation of the cDNA yielded a protein product of approximately 33 kDa. Northern and Western blot analyses, using the cDNA and antirecombinant protein antibody, revealed its expression exclusively confined to the kidney. Like ALR2, the expression was up-regulated in diabetic kidneys. Its mRNA and protein expression was restricted to renal proximal tubules. The gene neither codistributed with Tamm-Horsfall protein nor aquaporin-2. The deduced protein sequence revealed an AKR-3 motif located near the N terminus, unlike the other AKR family members where it is confined to the C terminus. Fluorescence quenching and reactive blue agarose chromatography studies revealed that it binds to NADPH with high affinity (K(dNADPH) = 66.9 +/- 2.3 nM). This binding domain is a tetrapeptide (Met-Ala-Lys-Ser) located within the AKR-3 motif that is similar to the other AKR members. The identified protein is designated as RSOR because it is renal-specific with properties of an oxido-reductase, and like ALR2 it may be relevant in the renal complications of diabetes mellitus.

Aldehyde Reductase↗
PubMed2000

Re-evaluation of exercise prescription for Japanese type 2 diabetic patients by ventilatory threshold.

Prescription of aerobic exercise for Type 2 diabetes mellitus (Type 2 DM) in clinical practice is frequently based on exercise intensity at maximum heart rate (60<HR(max)<79%), heart rate reserve (50<HR(reserve)<74%), and rating of perceived exertion (12<RPE<13). We examined these parameters in Japanese males with Type 2 DM at ventilatory threshold (VT) to investigate the exercise capacity of Type 2 DM patients and re-evaluate the exercise prescription. Fifty-six Japanese Type 2 DM males without autonomic neuropathy [age, 53.5+/-7.7 years; body mass index (BMI), 23.7+/-3.6 kg/m(2)] were enrolled and compared with 56 age- and BMI-matched healthy Japanese males. VT was determined breath by breath during exercise test using a ramp protocol and rates of oxygen consumption (VO(2)), work rate (WR), HR, DeltaHR, %HR(max), %HR(reserve), and RPE were measured at VT. Type 2 DM patients had significantly lower VO(2) (3.6+/-0.4 metabolic equivalents (METs)) and WR (62+/-14 W) than controls (VO(2), 3.9+/-0.6 METs; WR, 74+/-13 W). %HR(reserve), (32.6+/-7.7%) was also significantly lower compared with controls (37.6+/-8.3%), while %HR(max), was not different. RPE was also similar in diabetics (12.4+/-1.5) and controls (12.9+/-1.2), however, it was significantly lower in diabetic patients aged 60-69 years (11.8+/-2.0) and those with distal symmetric sensory neuropathy (12.2+/-1.0). Our results indicate reduced exercise capacity in Japanese Type 2 DM males and the exercise intensity of 60%HR(max), 30%HR(reserve), and RPE 12 is recommended in elderly diabetics and those with diabetic sensory neuropathy.

Blood Pressure↗
PubMed2000

Clinical evaluation of muscle strength in 20-79-years-old obese Japanese.

It is well known that obesity is closely related to non-insulin-dependent diabetes mellitus, hyperlipidemia, hypertension and cardiovascular disease, and the insulin resistance associated with obesity is supposed to play a central role for the development of these diseases. Thus, effective prevention and treatment of obesity need to be explored. In 357 obese (body mass index > or =26.4) subjects, aged 20-79 years, grip and leg strength were determined and compared with age- and sex-matched 1683 nonobese control subjects. Age-dependent alteration of body composition, evaluated by waist-hip ratio and the relative fat mass volume, was also compared. Finally, the relationship between the number of risk factors related to atherosclerosis and muscle strength was evaluated. Grip and leg strength in obese subjects were obviously stronger than controls under the age of 60 in both sexes. However, in the subjects over 60 years old, muscle strength was similar between obese subjects and controls. Weight bearing index (WBI) (leg strength (kg)/body weight (kg)) in obese subjects was remarkably lower than that in controls in all generations. In obese subjects, the waist-hip ratio and relative percentage of fat increased with aging, and obese subjects with multiple risk factors had higher waist-hip ratio and a tendency for lower muscle strength. Reduced WBI was considered to be a fundamental feature of obese subjects, and obese subjects increased fat composition with aging, which may be linked with low muscle strength. Thus, we need to design the most effective protocols to maximize and maintain quantitative and qualitative properties of muscle.

Adult↗
PubMed2000

Familial interstitial nephritis with progressive renal failure.

We describe a 53-year-old woman with chronic interstitial nephritis and asymptomatic impairment of renal function. Seven members of her family were suffering from renal failure and underwent hemodialysis. At the time of their hospital admissions, they had shown evidence of end-stage renal failure at 40 to 50 years of age. Lack of proteinuria, hematuria, hypertension, hyperuricemia, hearing loss, and visual impairment were present before the deterioration of the renal function. Renal biopsy of the presented case indicated chronic interstitial nephritis without glomerular basement membrane abnormalities. Progressive decline of renal function and the inheritance pattern of autosomal dominance in this family suggested the diagnosis of familial interstitial nephritis.

Female↗
PubMed2000

Efficacy of galectins in the amelioration of nephrotoxic serum nephritis in Wistar Kyoto rats.

BACKGROUND: Galectins are characterized by specific affinity for beta-galactoside sugars, and they play a role in diverse biological processes, including cell adhesion, cell proliferation, and apoptosis. Galectin-1, -3, and -9 have been implicated in modulating the immune response. METHODS: Nephrotoxic serum nephritis, which is characterized by crescent formation and glomerular influx of CD8+ cells into glomerular capillaries, was induced in Wistar Kyoto (WKY) rats by injecting rabbit antiglomerular basement membrane serum. Following induction, the rats were treated either with phosphate-buffered saline or dexamethasone, galectin-1, galectin-3, or galectin-9 on alternate days and were sacrificed at day 14. At day 8, splenic lymphocytes were isolated and employed for terminal deoxytransferase-mediated uridine triphosphate nick end-labeling (TUNEL) assay to assess the degree of apoptosis, and the kidneys were utilized to determine the extent of influx of CD4(+) and CD8(+) cells and glomerular damage. RESULTS: Dexamethasone induced a marked apoptosis of splenic CD4(+) and CD8(+) cells, and it inhibited the production of anti-rabbit IgG and the influx of CD8+ cells and macrophages into the renal glomeruli. Crescent formation and excretion of urinary proteins were also reduced. Galectin-9 failed to induce apoptosis in the CD4(+) cells; however, it induced apoptosis in the CD8(+) cells and inhibited the infiltration of CD8(+) cells. Although galectin-1 and -3 did not induce the apoptosis in the T cells, they inhibited the accumulation of macrophages in the renal glomeruli. Like dexamethasone, the galectins also reduced the crescentic formation, proliferation of glomerular cells, and excretion of urinary proteins. CONCLUSIONS: Galectin-9 selectively induces apoptosis of the activated CD8(+) cells, while the macrophage influx into the kidney is modulated by all three galectins. This finding raises an interesting possibility for the utility of galectins in the modulation of macrophages that are involved in immune-mediated glomerular diseases.

Adjuvants, Immunologic↗
PubMed2000

Expression characteristics and relevance of sodium glucose cotransporter-1 in mammalian renal tubulogenesis.

Expression and role of sodium glucose cotransporter (SGLT-1) in tubulogenesis were investigated during renal development. A mouse SGLT-1 cDNA was cloned, and it had substantial homology with human and rat forms. Four mRNA transcripts were detected, which differed in size from other species. SGLT-1 transcripts were detected at day 13 of gestation, and their expression increased during later stages extending into the postnatal period. A high mRNA and protein expression of SGLT-1 was seen in tubular segments of the inner cortex and outer medulla at day 16, and it was developmentally regulated. Treatment with SGLT-1 antisense selectively decreased the population of tubules in the metanephric explants. Expression of glomerular mRNA and WGA binding were unchanged. SGLT-1 activity, as measured by [(14)C]methyl-alpha-D-glucopyranoside uptake, increased during gestation in the tubular segments where it is expressed. Glucose uptake was inhibited by the treatment with SGLT-1 antisense and D-galactose. The data suggest that SGLT-1 exhibits a restricted spatiotemporal expression with functional activity confined to the corresponding tubular segments, and it selectively maintains renal tubulogenesis during development.

Amino Acid Sequence↗
PubMed2000

Turnover procedure.

Sternal turnover can be considered an orthotopic bone transplantation in reverse position. It yields immediate stability of the chest and good cosmetic results. Procedures using "pedicled plastrons" (rectal muscles, internal mammary arteries) have been reported; a large series of 300 cases, however, shows satisfying results with free grafts. Technetium-99m isotope studies yielded visualization of the plastron 1 year after sternal turnover. After redo-operations, histopathologic studies gave nearly normal sternal bone marrow findings.

Bone Transplantation↗
PubMed2000

Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats.

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is an animal model of type 2 diabetes, characterized by abdominal obesity, insulin resistance, hypertension, and dyslipidemia. To elucidate the underlying molecular mechanism of obesity and its related complications, we used representational difference analysis and identified the genes more abundantly and specifically expressed in the visceral adipose tissue (VAT) of obese OLETF rats compared with the diabetes-resistant counterpart, that is, Long-Evans Tokushima Otsuka (LETO) rats. By Northern blot analysis, we confirmed the differential expression of 13 genes, including 3 novel genes. The upregulated expression of well-characterized lipid metabolic enzymes, such as lipoprotein lipase, phosphoenolpyruvate carboxykinase, and cholesterol esterase, were observed in VAT of OLETF rats. We demonstrated the differential expression of secreted proteins in VAT of OLETF rats, such as thrombospondin 1 and contrapsin-like protease inhibitor. In contrast to lipid enzymes, the secreted proteins revealed exclusive mRNA expression and they were not detected in VAT of LETO rats. Furthermore, the novel genes OL-16 and OL-64 were also expressed specifically in VAT of OLETF rats and were absent in that of LETO rats and other tissues, including subdermal and brown adipose tissues. The C-terminal partial amino acid sequence of OL-64 revealed that it showed approximately 40% homology with alpha(1)-antitrypsin and it seemed to be a new member of the serine proteinase inhibitor (SERPIN) gene family. VAT of OLEFT rats had a unique gene expression profile, and the accumulated VAT-specific known and novel secreted proteins may play a role(s) in the pathogenesis of obesity and its related complications.

Adipose Tissue↗
PubMed2000

Fatal pancreatitis associated with systemic amyloidosis in a rheumatoid arthritis patient.

We report here a case of severe acute pancreatitis associated with systemic AA amyloidosis in a 69-year-old rheumatoid arthritis (RA) patient. AA amyloid deposition was detected on the walls of small pancreatic arteries and arterioles. The acute pancreatitis was resistant to various interventions, and acute necrotizing pancreatitis and multiple organ failure developed. Although AA amyloidosis in RA patients is rarely complicated with acute pancreatitis, acute pancreatitis in such cases could be severe and intractable and might result in a fatal outcome.

Aged↗
PubMed1999

Tubulointerstitial nephritis antigen: an extracellular matrix protein that selectively regulates tubulogenesis vs. glomerulogenesis during mammalian renal development.

Tubulointerstitial nephritis antigen (TIN-ag) is an extracellular matrix protein and is expressed in the renal tubular basement membranes. Its role in metanephric development was investigated. TIN-ag cDNA, isolated from the newborn mouse library, had an ORF of 1,425 nucleotides, a putative signal sequence, and an ATP/GTP-binding site. The translated sequence had approximately 80% identity with rabbit TIN-ag. Among various tissues, TIN-ag mRNA was primarily expressed in the newborn kidney. In the embryonic metanephros, TIN-ag expression was confined to the distal convolution or pole of the S-shaped body, the segment of the nascent nephron that is the progenitor of renal tubules. Treatment with TIN-ag antisense oligodeoxynucleotide induced dysmorphogenesis of the embryonic metanephroi, malformation of the S-shaped body, and a decrease in the tubular population, whereas the glomeruli were unaffected. Treatment also led to a decrease of TIN-Ag mRNA, de novo synthesis of TIN-ag protein, and its antibody reactivity. The mRNA expression of glomerular epithelial protein 1 (a marker for renal podocytes), anti-heparan-sulfate-proteoglycan antibody reactivity, and wheat germ agglutinin lectin staining of the metanephros were unaffected. The anti-TIN-ag antibody treatment also caused deformation of the S-shaped body and a reduction in the tubular population, whereas the glomeruli were unchanged. The data suggest that the TIN-ag, unlike other basement membrane proteins, selectively regulates tubulogenesis, whereas glomerulogenesis is largely unaffected.

Amino Acid Sequence↗
PubMed1999

Integrins mediate the inhibitory effect of focal adhesion on angiotensin II-induced p44/42 mitogen-activated protein (MAP) kinase activity in human mesangial cells.

Previously, we reported that the formation of focal adhesion accelerated by accumulation of extracellular matrices may inhibit the angiotensin II-stimulated proliferation of human mesangial cells (HMCs). The process is regulated by p44/42 MAP kinase activity through the mediation of paxillin and GTPase activating proteins. In this report, we investigated the effect of integrin molecules on the angiotensin II-induced p44/42 MAP kinase activation in non-adherent HMCs. The results demonstrated that incubation of cells with both antibody to integrin beta(1) chain (K20) and GRGDS peptide induced integrin clustering, paxillin aggregation, and marked suppression of angiotensin II-induced p44/42 MAP kinase activation. On the other hand, incubation of cells with K20 alone induced integrin clustering without paxillin aggregation and the suppressive effect on angiotensin II-stimulated p44/42 MAP kinase activity. Our results strongly suggest the pivotal role of integrins in the inhibitory effect of focal adhesion on p44/42 MAP kinase activity, the checking system against angiotensin II-induced MAP kinase overactivation.

Angiotensin II↗
PubMed1999

Cloning of rat fibrillin-2 cDNA and its role in branching morphogenesis of embryonic lung.

Fibrillin-2 is an extracellular matrix protein. It is associated with elastic fibers in several tissues and is believed to serve as a ligand for alphavbeta3 integrin, the latter being a known morphogen. In this study, the role of fibrillin-2 in lung development was investigated. Also, rat fibrillin-2 cDNA was isolated and sequenced and its spatiotemporal expression determined. It had approximately 88% homology with human fibrillin-2 and had Ca(2+) binding epidermal growth factor-like domains, transforming growth factor-beta binding protein motifs, and two RGD binding sites. Northern blot analysis revealed an approximately 10-kb transcript, and fibrillin-2 expression was developmentally regulated, and it paralleled that of tropoelastin. At day 13 of gestation, fibrillin-2 was expressed in the mesenchyme and at the epithelial:mesenchymal interface. From day 13 to 19 of gestation, its expression intensified and was confined around the tracheobronchial airways, while it lessened during the postnatal period. Immunoprecipitation revealed an approximately 350-kDa band by SDS-PAGE. Treatment with fibrillin-2 antisense oligodeoxynucleotide induced dysmorphogenesis of the lung explants. They were smaller and had rudimentary lung bud branches, collapsed conducting airways, and loose expanded mesenchyme. Concomitantly, fibrillin-2 mRNA, antibody reactivity in the explants, and fibrillin-2-specific radioincorporation were reduced. Anti-alphav and -laminin antibody reactivity and their respective incorporated specific radioactivities were unaltered. These data indicate that fibrillin-2 modulates organogenesis of the lung in the context of epithelial:mesenchymal interactions. Conceivably, the collapse of the conducting airways may also be related to the perturbed biology of the fibrillin-2 interacting protein, i.e., elastin, the latter being critical for the normal biophysiology of the lungs.

Actins↗
PubMed1999

Signaling transduction pathway of angiotensin II in human mesangial cells: mediation of focal adhesion and GTPase activating proteins.

Human mesangial cells (HMCs) respond to angiotensin II stimulation, which modulates their physiological activities, i.e., contraction and proliferation. It has been revealed that focal adhesion kinase (FAK) and paxillin participate in the angiotensin II-mediated signaling and cytoskeletal rearrangements at focal adhesion. We investigated the influences of cell adhesion upon angiotensin II effects in HMCs. In adherent cells, both FAK and paxillin were tyrosine phosphorylated by angiotensin II, while the cell detachment completely inhibited the tyrosine phosphorylation of paxillin. Activation of p44/42 mitogen-activated protein (MAP) kinase by angiotensin II was accentuated in suspended cells. Moreover, p190, a member of Rho GTPase activating protein (GAP), and RasGAP were coprecipitated with paxillin in adherent cells and angiotensin II stimulation reduced the formation of paxillin-p190 and paxillin-RasGAP complexes. These results suggest that the formation of focal adhesion complexes accelerated by accumulation of mesangial matrices may inhibit the proliferation of HMCs by modulating MAP kinase activity and be related to mesangial cell depletion.

Angiotensin II↗