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Yukishige Yanagawa

Publications and source records attributed to Yukishige Yanagawa.

13 recordsLinked to original sources
PubMed2007

Renal effects of beta2-adrenoceptor agonist and the clinical analysis in children.

The objectives of the present study were to define the contribution of beta2-adrenoceptors (beta2-ARs) agonists to renal physiology and to investigate whether over-expression of renal beta2-ARs might be implicated in the pathogenesis of renal dysfunction in children as an adverse effect of beta2-AR activation. The renal functional responses to the systemic injection of the beta2-AR agonist terbutaline in Wistar rats over-expressing renal beta2-AR were compared with those of nontreated rats. Furthermore, we evaluated intrarenal beta2-AR expression in 34 children (age 2-15 y) and the changes in serum creatinine levels of 99 children (age 1-15 y) who received beta2-AR agonists. The animal study showed that the suppression of glomerular function by terbutaline was associated with a reduction in systemic blood pressure and over-expression of renal beta2-ARs. Moreover, in rats over-expressing renal beta2-ARs, administration of terbutaline resulted in a high mortality rate after a lipopolysaccharide challenge. The clinical study showed that renal beta2-AR expression gradually increased with age and was up-regulated by steroid therapy. These findings indicate that the renal dysfunction caused by beta2-AR agonists can be explained, at least partly, by enhanced beta2-AR expression in the kidney. This may have important implications for the use of beta2-AR agonists in the treatment of sick children with, for example, steroid therapy or endotoxemia.

Adolescent↗
PubMed2006

Renal hypouricemia in school-aged children: screening of serum uric acid level before physical training.

We present two cases of a 12-year-old Japanese boy and a 14-year-old Japanese girl who had exercise-induced acute renal failure (ARF). They experienced general fatigue, nausea/vomiting, and vague discomfort in the abdomen after physical exercise at school. In case of the boy, abdominal pain subsided, but renal dysfunction lasted 17 days, with peak levels of creatinine 9.4 mg/dl and uric acid 11.3 mg/dl. On the other hand, as the girl had suffered from hypouricemia before, she followed a doctor's guidance on prevention of ARF. Consequently, she was promptly diagnosed as having exercise-induced ARF associated with hypouricemia, and rapidly recovered from ARF within a week. The difference between their clinical courses suggested a possibility that previous laboratory evaluation of serum uric acid assisted in the management of exercise-induced ARF associated with hypouricemia. School-aged children, especially Japanese and Asian, may be advised to have their serum uric acid measured before starting physical training at school.

Acute Kidney Injury↗
PubMed2005

Adenoviral delivery of the beta2-adrenoceptor gene in sepsis: a subcutaneous approach in rat for kidney protection.

Successful gene therapy requires gene delivery that is efficient, has an optimal route of administration and has biosafety. The aims of the present study were to evaluate the safety and applicability of the subcutaneous delivery route for adenoviral transgenes containing the human beta(2)-adrenoceptor (adeno-beta(2)-AR) and to investigate whether this approach prevented renal dysfunction in a rat model of endotoxaemic shock induced by LPS (lipopolysaccharide). Subcutaneous administration of adeno-beta(2)-AR (a total of 10(10) viral particles) significantly increased beta-AR density in the kidney, lung and liver, but was without effect on physiological and plasma biochemical parameters. Moreover, this dose of virus did not cause any of the potential toxic responses of viral administration, such as inflammation and tissue TNF (tumour necrosis factor)-alpha expression. Although the LPS challenge caused a decrease in glomerular filtration rate, fractional excretion of sodium and renal beta-AR density in all groups, the reduction in renal function was significantly less in the rats given adeno-beta(2)-AR compared with non-treated rats. Thus, although further evaluation will be required, this initial study demonstrated that the subcutaneous injection of adeno-beta(2)-AR was efficient, comparatively non-pathogenic and potentially therapeutic to deal with acute renal failure associated with sepsis.

Acute Kidney Injury↗
PubMed2004

beta(2)-Adrenoceptor activation attenuates endotoxin-induced acute renal failure.

Abnormalities in the beta(2)-adrenergic control of organ function have been implicated in the pathogenesis of several disease states, such as septic shock. The objectives of the present study were to define the contribution of beta(2)-adrenoceptors (beta(2)-AR) to normal renal physiology and to investigate whether overexpression of renal beta(2)-AR might be potentially beneficial in preventing progressive renal damage associated with endotoxemia. Adenoviral transgenes containing the human beta(2)-AR (Adeno-beta(2)-AR) were constructed and delivered into the rat kidney by means of intraparenchymal injections. Administration of 10(9) total viral particles of Adeno-beta(2)-AR induced an approximately threefold increase in beta(2)-AR density in the renal tissue, which 2 wk after delivery, enhanced GFR and sodium reabsorption compared with control rats. The enhanced GFR was abolished by the addition of the beta(2)-AR antagonist, ICI 118,551. Administration of lipopolysaccharide (LPS) caused a reduction in GFR, beta(2)-AR density, and cAMP together with enhanced TNF-alpha mRNA in the kidney. In rats overexpressing beta(2)-AR, the reduction in baseline GFR and elevation of TNF-alpha mRNA and leukocyte infiltration into the kidney associated with the endotoxin were blocked. These findings suggested the possibility that a renal-specific overexpression of beta(2)-AR preserves basal renal function in response to a ligand-independent beta(2)-AR activation and that the delivery of Adeno-beta(2)-AR gene is a potential novel therapeutic strategy for treatment of acute renal failure associated with sepsis.

Acute Kidney Injury↗
PubMed2004

[Beta 2-adrenoceptor function in the kidney].

The majority of beta(2)-adrenoceptor (beta(2)-AR) agonists is eliminated via the kidneys as an unchanged substance. It is likely that such agents will exert pharmacological effects during their passage through the nephron. However, these pharmacological effects have, to our knowledge, not been taken into consideration when using these compounds in clinical practice because the role of beta(2)-AR in the regulation of renal function remains unclear. Renal beta(2)-ARs are predominantly localized to the proximal tubular epithelia and the membranes of smooth muscle cells from renal arteries. From this morphologic evidence, it is proposed that beta(2)-AR activation may regulate glomerular function and thereby sodium and water balance in the nephron segments. Actually, beta(2)-AR agonists given acutely cause a marked decrease in glomerular filtration rate. On the other hand, beta(2)-AR agonists inhibit the renal production of inflammatory cytokines such as TNF-alpha. Furthermore, the administration of beta(2)-AR agonists is found to attenuate apoptosis associated with shigatoxin in the hemolytic uremic syndrome (HUS). Increased understanding of the pharmacological basis of beta(2)-AR function in the kidney provides important new information relevant to the clinical use of beta(2)-AR agonists in airway diseases and potential applications of these drugs in renal inflammation and injury associated with sepsis or HUS.

Adrenergic beta-Agonists↗
PubMed2003

Beta2-adrenoceptor activation inhibits Shiga toxin2-induced apoptosis of renal tubular epithelial cells.

Apoptosis is regulated by several pathways, such as caspases, mitogen activated protein kinase (MAPK) and cAMP/cAMP-dependent protein kinase A (PKA) cascade. This study investigated the effect of beta(2)-adrenoceptor activation on Shiga toxin (Stx)2-induced apoptosis in renal tubular cells and the contribution of these signalling pathways. Cultured human adenocarcinoma-derived tubular cells were exposed to Stx2 (64 pg/mL) for 2-24hr following the addition of the beta(2)-adrenoceptor agonist (terbutaline) to the incubation medium. Stx2-induced apoptosis and its amelioration by beta(2)-adrenoceptor activation was confirmed using DNA degradation assays and by flow cytometry for annexin V, mitochondrial membrane potential and caspase(-3 and -7) activity. Exposure of cells to Stx2 for 24hr increased the DNA fragmentation to 11.6+/-0.9%, compared to 3.3+/-0.2% in control cells (P<0.05) but was decreased to approximately 5-7% (P<0.05) in the presence of terbutaline. Furthermore, Stx2-stimulated apoptosis, detected by TUNEL, annexin V and mitochondrial potential, was inhibited by terbutaline (P<0.05) which was prevented by cAMP-PKA inhibitors and a beta(2)-adrenoceptor antagonist. However, inhibition of Stx2-mediated caspase activity by terbutaline was partially blocked by cAMP-PKA inhibitors. On the other hand, p38MAPK inhibition by terbutaline prevented Stx2-induced apoptosis and caspase activity through a cAMP-independent pathway via beta(2)-adrenoceptor. These data indicate that beta(2)-adrenoceptor activation can inhibit Stx2-induced apoptosis of the cells, which may be caused by a reduction in caspase activity through cAMP-PKA activation and the p38MAPK pathway.

Annexin A5↗
PubMed2003

[Basic and clinical evaluation of the new rapid diagnostic kit for detecting group A streptococci with the immunochromatographical method].

Basic and clinical performance of a new diagnostic kit that detects Group A Streptococci by an immunochromatographical method, QuickVue Dipstick Strep A (Quidel Corporation; San Diego, CA) were evaluated. In basic specificity study, the QuickVue Dipstick Strep A showed positive reaction only to group A Streptococci strains among 34 strains of 10 species of bacteria. In detection limit study, the QuickVue Dipstick Strep A had a capacity to detect Group A Streptococci in 1.0 x 10(4); cfu/ml (1.0 x 10(3) cfu/test). This sensitivity was about 6 times higher than that of the existing similar immunochromatographical test, STREP A TESTPACK Plus (TESTPACK, Abbott Japan, Tokyo). In clinical study compared with bacterial culture test using 100 patients' throat swab specimens, the QuickVue Dipstick Strep A showed a sensitivity of 94.4% (34/36), a specificity of 100% (64/64) and an accuracy of 98% (98/100). Furthermore in correlation study with the reference test, TESTPACK, the QuickVue Dipstick Strep A showed 100% agreement (34 positive and 66 negative specimens). As the QuickVue Dipstick Strep A has several advantages as not only simple operation, rapid reaction and good performance but also easy storage (under room temperature), compact size and minimum waste products, we conclude that this new test is useful as Point-of-Care Testing kit and plays a peripheral role in the diagnosis of Group A Streptococci infection and pertinent medical treatment by antibacterial agents.

Humans↗
PubMed2002

Role of angiotensin II-induced cAMP in mesangial TNF-alpha production.

Previous findings indicated that cAMP had an inhibitory effect of on tumour necrosis factor (TNF)-alpha production. Angiotensin II (Ang II) may activate the cAMP-protein kinase A (PKA) pathway in renal mesangial cells through synthesis of prostaglandins (PGs) and the possibility arises that inhibition of Ang II-induced cAMP formation might result in the overproduction of TNF-alpha in the cell and this hypothesis was tested in the present study. Rat mesangial cells were exposed to Ang II in the presence or absence of cyclooxygenase inhibitor (indomethacin) or cAMP-PKA inhibitor (H-89). Exposure of mesangial cell to Ang II (10(-6)M-10(-8)M) significantly increased intracellular cAMP level through type 1 Ang II receptor but had no effect on TNF-alpha protein release, transcriptional activity, or mRNA. However, following the addition of indomethacin or H-89, Ang II significantly increased TNF-alpha release, transcriptional activity, and mRNA level. These data suggested that in mesangial cells after blockade of cAMP-PKA by PG inhibition, Ang II was capable of stimulating TNF-alpha transcription which subsequently increased TNF-alpha mRNA accumulation and protein release.

Angiotensin II↗
PubMed2002

Prenatal diagnosis of Menkes disease by genetic analysis and copper measurement.

Carrier detection for 12 women and prenatal diagnosis for six fetuses in Japanese families with a patient with Menkes disease (MNK) were performed by gene analysis and/or measurement of the copper concentration in cultured cells. Six out of eight mothers of MNK patients were carriers while two (25%) were not carriers. Two unrelated patients showed the same mutation (R986X): one patient's mother was a carrier while the other was not. One male and three female fetuses did not have the same mutant allele as the respective MNK proband and have been healthy since birth. One female fetus had the same mutant allele as her affected brother. Gene analysis is very useful and reliable, although such examination is only indicated in families in which a mutation has been identified. In one family in which a mutation in ATP7A was not found, cultured amniocytes from a male fetus had a high copper concentration. Thus after his birth, the biochemical findings confirmed the presence of MNK and early treatment was started. As his early treatment with parenteral copper-histidine prevented the neurological disorders effectively, prenatal diagnosis is very important.

Amniocentesis↗
PubMed2002

Suppression of endotoxin-induced renal tumor necrosis factor-alpha and interleukin-6 mRNA by renin-angiotensin system inhibitors.

The present study was designed to clarify the role of angiotensin II (Ang II) in modulating renal tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) production and to investigate the effect of one dose of Ang II inhibitor on cytokines production following lipopolysaccharide (LPS) to cause endotoxemia. Two studies were performed: 1) Ang II was infused intravenously at a rate of 0.2 microg/kg per minute for 4 h in rats and then kidneys were collected to assay TNF-alpha and IL-6 mRNA levels; 2) Four-week-old Wistar rats pre-treated with angiotensin-converting enzyme inhibitor, enalapril, or type I Ang II-receptor antagonist, TCV-116, were injected with LPS (0.1, 0.5, 1.0 mg, i.p.), and then 2 or 4 h later, kidneys were collected to assay TNF-alpha, IL-6, renin and angiotensinogen mRNA levels. After a 4-h intravenous infusion of Ang II, renal TNF-alpha or IL-6 mRNA level significantly increased 1.9-fold or 2.1-fold (each P<0.05) to the control level, respectively. LPS stimulated TNF-alpha, IL-6 and angiotensinogen mRNA levels in the kidney but in rats given enalapril or TCV-116, LPS-induced IL-6 and TNF-alpha mRNA levels were completely suppressed (each P<0.05). This suggests that a single dose of renin-angiotensin system inhibitor suppressed renal IL-6 and TNF-alpha production and may prevent cytokine-induced renal damage during endotoxemia.

Angiotensin II↗
PubMed2001

Activation of beta(2)-adrenoceptor prevents shiga toxin 2-induced TNF-alpha gene transcription.

Exposure of renal tubular epithelial cells to shiga toxin 2 (Stx-2) causes cytotoxicity, and the potency of this toxin is enhanced in the presence of tumor necrosis factor-alpha (TNF-alpha). It has been shown that Stx-2 induces TNF-alpha production and that activation of beta(2)-adrenoceptors downregulates TNF-alpha. However, little is known about the signaling pathway by which beta(2)-adrenoceptor agonists suppress the Stx-2-induced TNF-alpha gene transcription. The possible signaling components involved in this pathway were investigated. Human adenocarcinoma-derived renal tubular epithelial cells (ACHN) were exposed to Stx-2 in the presence or absence of a beta(2)-adrenoceptor agonist. Mitogen-activated protein kinase (MAPK), activating protein-1 (AP-1), and nuclear factor-kappa B (NF-kappa B) were measured to evaluate the regulatory mechanisms involved in TNF-alpha gene transcription. Stx-2 (4 pg/ml) stimulated MAPK (p42/p44, p38) and AP-1 and increased TNF-alpha promoter activity by 2.4-fold. The increase in TNF-alpha was attenuated by both a p42/p44 inhibitor, PD098059 (10(-6) M), and a p38 inhibitor, SB203580 (10(-6) M), and AP-1-binding activity was inhibited by PD098059. Terbutaline (10(-6) M to 10(-8) M) suppressed MAPK (p42/p44, p38), NF-kappa B (p50, p65), and TNF-alpha promoter activity in a dose-dependent way that was prevented by the beta(2)-adrenoceptor antagonist, ICI118,551. However, inhibition of MAPK (p42/p44) and TNF-alpha promoter activity was partially prevented by the cAMP-protein kinase (PKA) inhibitors, H-89 (5 x 10(-6) M) and KT5720 (10(-5) M), whereas the suppression of p38 MAPK or NF-kappa B (p50) was not blocked by these inhibitors. The suppression of NF-kappa B (p65) was completely overcome by H-89 or KT5720. In summary, the downregulation of TNF-alpha transcription by terbutaline was mediated by an inhibitory effect of beta(2)-adrenoceptor activation on MAPK (p42/p44, p38) and NF-kappa B (p50/p65), which were exerted through a cAMP-PKA pathway and a cAMP-independent mechanism. It is likely that cAMP-PKA and MAPK (p42/p44, p38) may play a critical role in the regulation of the Stx-2-induced TNF-alpha transcription via beta(2)-adrenoceptor activation.

Adrenergic beta-Agonists↗