Biomedical subjects

Ken-ichi Yoshida

Publications and source records attributed to Ken-ichi Yoshida.

At least 19 recordsLinked to original sources

PubMed2006

Ischemia promotes calpain-mediated degradation of p120-catenin in SH-SY5Y cells.

p120-catenin contributes to the cadherin-mediated adhesion and aggregation of cells. mu-Calpain was activated and p120-catenin was degraded after 36 h of ischemia in differentiated SH-SY5Y cells. Calpain inhibitors Cbz-Val-Phe-H (MDL28170, 20 microM) and N-acetyl-leucyl-leucyl-norleucinal (ALLN, 20 microM) increased the levels of dephosphorylated p120-catenin, aggregation, and cell survival as detected by reduced LDH release in ischemic cells. However, a proteasome inhibitor lactacystin had no such effects. This is the first report of the calpain-mediated degradation of p120-catenin and an association between the level of dephosphorylated p120-catenin and cell aggregation in ischemic neuronal cells.

Acetylcysteine↗

PubMed2006

MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 6: exploration of aromatic substituents.

A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, derivatized at the 2-position with aromatic substituents, were synthesized by the Suzuki cross-coupling method and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the anti-pseudomonas beta-lactam aztreonam (AZT) in Pseudomonas aeruginosa. By incorporating hydrophilic substituents onto the aryl nucleus, we found a morpholine analogue that possessed improved solubility, retained activity in vitro, and displayed potentiation activity in vivo in a rat model of P. aeruginosa pneumonia.

Animals↗

PubMed2006

Spontaneous rupture of the urinary bladder presenting as oliguric acute renal failure.

A 64-year-old female was admitted to hospital for acute abdominal pain with ascites. The patient had received postoperative pelvic irradiation for carcinoma of the uterine cervix 7 years previously. Serum creatinine (Scr) was elevated to 2.70 mg/dl, and urinary output was reduced to below 200 ml/day. Cystoscopy revealed a small perforation from the bladder diverticulum. Following transurethral catheterization, urinary output was promptly increased, and Scr was returned to 0.65 mg/dl 4 days later. This rare case suggested that spontaneous rupture of the urinary bladder following postoperative radiotherapy could occur very late with laboratory features of oliguric acute renal failure.

Abdomen, Acute↗

PubMed2006

4-Hydroxynonenal modifies IgA in rat intestine after lipopolysaccharide injection.

The lipid peroxide 4-hydroxynonenal (HNE) was measured in rat intestinal mucosa after lipopolysaccharide (LPS) injection (0.5 mg/kg, ip) by a highly sensitive time-resolved fluoroimmunoassay. HNE was increased, with a small peak at 20 min followed by a sustained elevation at 2-4 h, after injection of LPS. Immunohistochemistry demonstrated enhanced labeling with anti-IgA and anti-HNE antibodies in the plasma cells followed by diffusion of the labeled materials into the submucosal tissue after LPS injection. Immunoprecipitation with anti-IgA antibody and Western blotting with anti-HNE antibody showed that IgA is modified with HNE after LPS injection. The HNE (5 microM-5 mM) modification in vitro reduced the bactericidal activity of IgA and anti-Escherichia coli serum. The HNE modification in vitro also promoted polymerization of IgA as shown by nondenaturing gel electrophoresis. This is the first demonstration of the modification of IgA with HNE in an in vivo model of intestinal inflammation as well as in vitro effects of HNE on bactericidal activity and polymerization of IgA. These findings will help in understanding the involvement of oxidative stress in the IgA-mediated immune response exerted by plasma cells in early intestinal inflammation.

Aldehydes↗

PubMed2006

Ischemic preconditioning protects cardiomyocytes against ischemic injury by inducing GRP78.

Ischemic preconditioning (IP) conferred by brief ischemia-reperfusion induces resistance to cell injury due to the following lethal ischemia. This study aimed to elucidate whether 78-kDa glucose-regulated protein (GRP78), a main ER molecular chaperone, contributes to IP-mediated protection against ischemic myocardial injury. In a rat coronary artery occlusion model, the GRP78 protein level increased to 210% of the sham level by early IP with three cycles of 4-min ischemia and 4-min reperfusion. The IP reduced infarct size in subsequent lethal ischemia. In primary cardiomyocytes, the simulated IP procedure, incubation in oxygen-glucose deprivation (OGD) medium, also increased the GRP78 expression and suppressed the cell death caused by lethal ischemia. Transfection of grp78 antisense oligonucleotide attenuated the IP-mediated resistance to ischemia. This study showed for the first time that early IP up-regulates myocardial GRP78. It was suggested that GRP78 induced by early IP contributes to protect cardiomyocytes against ischemic injury.

Animals↗

PubMed2006

Ischemic preconditioning or p38 MAP kinase inhibition attenuates myocardial TNF alpha production and mitochondria damage in brief myocardial ischemia.

Coronary artery occlusion increased the TNF alpha level in the membrane fraction of the rat heart, almost maximally at 30 min. TNF alpha immunofluorescence labeled streak-like reticular structures inside of the cardiomyocyte but not vascular or interstitial cells in myocardial ischemia. Immuno-electron microscopy confirmed the localization of TNF alpha between myofibrils, mitochondria, or other membrane structures in the ischemic cardiomyocyte. Ischemic preconditioning (IP) is the protection of myocardium conferred by cycles of brief ischemia-reperfusion. The increases in TNF alpha production, as well as phosphorylation of p38 MAP kinase and S6 kinase after ischemia were inhibited by IP or p38 MAP kinase inhibitors (SB203580, FR167653). TNF alpha production appeared to be regulated possibly at the post-transcriptional step by ribosomal S6 phosphorylation given that IP did not suppress TNF alpha mRNA up-regulation and was independent of NFkappaB activation. Electron microscopy (EM) showed mitochondria damage in ischemic cardiomyocyte, which was inhibited either by IP or SB203580. This is the first demonstration of the TNF alpha up-regulation in membrane structures of ischemic cardiomyocyte through p38 MAP kinase-mediated post-transcriptional mechanism, in association with mitochondrial damage.

Animals↗

PubMed2006

A case of sudden death after intramuscular injection of butylscopolamine bromide.

A 40-year-old man experienced cardiopulmonary arrest after intramuscular injection of 20 mg of butylscopolamine bromide. No pathological changes were found at autopsy, and 1.19 microg/mL of butylscopolamine bromide was detected in his serum. Since he had taken no other drugs, his severe symptoms were thought to have been caused by an anaphylactic reaction to butylscopolamine bromide. Butylscopolamine bromide has been used for many years worldwide, and is considered to be a safe drug, with no reports of severe side effects following intramuscular injection. Since an anaphylactic reaction may not be related to a particular medication, the possibility of such a severe reaction must be considered, even during administration of an ostensibly safe drug such as butylscopolamine bromide.

Adult↗

PubMed2006

Death due to duodenal obstruction in a patient with an eating disorder: a case report.

OBJECTIVE: A 30-year-old woman with a 2-year history of bulimia nervosa and severe abdominal pain after excessive food consumption visited our emergency room. Her abdomen showed marked generalized distension. METHOD: Aspiration of the gastric contents was not successful, and despite efforts to resuscitate her, the patient died. RESULT: An autopsy showed a markedly distended stomach containing approximately 6,500 ml of solid foods. The aortomesenteric distance was <1.0 cm and the aortomesenteric angle was <20 degrees, suggesting superior mesenteric artery (SMA) syndrome may have been a cause of death. CONCLUSION: However, her condition was also consistent with duodenal obstruction due to a heavy stomach and high intra-abdominal pressure, and her cause of death was diagnosed as intestinal obstruction due to an excessive volume of food.

Adult↗

PubMed2006

Predicting metals sensed by ArsR-SmtB repressors: allosteric interference by a non-effector metal.

Many bacterial genomes encode multiple metal-sensing ArsR-SmtB transcriptional repressors. There is interest in understanding and predicting their metal specificities. Here we analyse two arsR-smtB genes, ydeT and yozA (now aseR and czrA) from Bacillus subtilis. Purified AseR and CzrA formed complexes in gel-retardation and fluorescence-anisotropy assays with fragments of promoters that were derepressed in DeltaaseR and DeltaczrA cells. Candidate (i) partly thiolate, alpha3-helix (for AseR) and (ii) tetrahedral, non-thiolate, alpha5-helix (for CzrA) metal binding sites were predicted then tested in vitro and/or in vivo. The precedents are for such sites to sense arsenite/antimonite (alpha3) and zinc (alpha5). This correlated with the respective metal inducers of AseR and CzrA repressed promoters in B. subtilis and matched the metals that impaired formation of protein-DNA complexes in vitro. The putative sensory sites of 1024 ArsR-SmtB homologues are reported. Although AseR did not sense zinc in vivo, it bound zinc in vitro exploiting alpha3 thiols, but AseR DNA binding was not impaired by zinc. If selectivity relies on discriminatory triggering of allostery not just selective metal binding, then tight non-effector metal complexes could theoretically inhibit metal sensing. AseR remained arsenite-sensitive in equimolar zinc, while CzrA remained zinc-sensitive in equimolar arsenite in vitro. However, cupric ions did not impair CzrA-DNA complex formation but did inhibit zinc-mediated allostery in vitro and prevent zinc binding. Access to copper must be controlled in vivo to avoid formation of cupric CzrA.

Allosteric Regulation↗

PubMed2006

Genetic modification of Bacillus subtilis for production of D-chiro-inositol, an investigational drug candidate for treatment of type 2 diabetes and polycystic ovary syndrome.

D-chiro-inositol (DCI) is a drug candidate for the treatment of type 2 diabetes and polycystic ovary syndrome, since it improves the efficiency with which the body uses insulin and also promotes ovulation. Here, we report genetic modification of Bacillus subtilis for production of DCI from myo-inositol (MI). The B. subtilis iolABCDEFGHIJ operon encodes enzymes for the multiple steps of the MI catabolic pathway. In the first and second steps, MI is converted to 2-keto-MI (2KMI) by IolG and then to 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione by IolE. In this study, we identified iolI encoding inosose isomerase, which converts 2KMI to 1-keto-D-chiro-inositol (1KDCI), and found that IolG reduces 1KDCI to DCI. Inactivation of iolE in a mutant constitutively expressing the iol operon blocked the MI catabolic pathway to accumulate 2KMI, which was converted to DCI via the activity of IolI and IolG. The mutant was able to convert at least 6% of input MI in the culture medium to DCI.

Bacillus subtilis↗

PubMed2006

[Standard surgery as part of the multidisciplinary treatment for pancreatic cancer].

Standardization of surgical procedure for pancreatic cancer has been recognized to be necessary and important these days. Recent studies appear to exhibit efficacy of the adjuvant chemoradiation therapy before or after pancreatic surgery. In this study, we examined the standard surgery as part of the multidisciplinary treatment for pancreatic cancer. Invasive ductal carcinoma of the pancreas was resected in 121 patients in our institution from 1992 through 2005. We stopped performing an extended lymphadenectomy with pancreatectomy in 2003, but the survival rates were not significantly different between the cases before and after 2003. We usually resect half of the nerve plexus around the superior mesenteric artery (SMA) as a standard procedure. When we achieved the microscopically curative resection (R0) even if the plexus around SMA or the portal vein was invaded, there were a few long survivors for more than five years. The R0 resection is the most important factor for prolonged survival. Pancreatectomy including removal of regional lymph nodes (D2) and half of the nerve plexus around SMA and combined resection of the infiltrated portal vein is thought to be a standard surgery from the viewpoint of decrease in morbidity and maintenance of curability.

Carcinoma, Ductal↗

PubMed2005

A fatal case of post-operative pulmonary thromboembolism with cosmetic liposuction.

Pulmonary thromboembolism (PTE) has been regarded as rare in Japan. However, PTE has been increasingly recognised because either of increased incidence, diagnostic progress, or social recognition. Recently, 10 Japanese Medical Associations have submitted preventive guidelines for PTE in post-operative patients and the government decided to fund this, as results of the increase in cases and concern regarding medical negligence. A fatal case of PTE after liposuction is reported. A female patient was in the home toilet after two days of immobilization following day-surgery liposuction. Clinicians must be aware of appropriate methods for the prevention of post operative PTE with cosmetic surgery.

Adult↗

PubMed2005

MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 5: Carbon-substituted analogues at the C-2 position.

A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, derivatized at the 2-position with carbon-linked substituents, were synthesized and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the anti-pseudomonas beta-lactam aztreonam (AZT) in Pseudomonas aeruginosa. Palladium-catalyzed cross-coupling methods were applied for the incorporation of aliphatic and aromatic substituents.

Anti-Bacterial Agents↗

PubMed2005

Carbon monoxide protects cardiomyogenic cells against ischemic death through L-type Ca2+ channel inhibition.

Carbon monoxide (CO) is known to protect myocardial and vascular cells against injuries due to ischemia-reperfusion or inflammation. We showed that a Ca(2+)-dependent protease calpain promotes necrotic cell death of cardiomyocyte-derived H9c2 cells due to hypoxia through alpha-fodrin proteolysis. Here, we show that ischemia induces necrotic cell death, which is inhibited by either CO, extracellular Ca(2+) deprivation or L-type Ca(2+) channel blockers. A whole cell patch-clamp experiment supports that CO inhibits L-type Ca(2+) channel mediated influx of Ca(2+) and the ischemic death of H9c2 cells.

Animals↗

PubMed2005

Usefulness of serum mast cell-specific chymase levels for postmortem diagnosis of anaphylaxis.

Chymase, a serine protease, is stored mainly in secretory granules of human mast cells. Serum chymase concentration was examined in 8 autopsy cases with anaphylaxis as well as in 104 control cases without anaphylaxis. It was detected in all 8 cases with anaphylaxis (range 3-380 ng/ml, mean 89.8 ng/ml), while it was detected in only 2 of the 104 controls and was below a detectable level (<3 ng/ml) in the other 102. Serum tryptase levels are known to be a diagnostic indicator of anaphylaxis, therefore the relationship between serum chymase and tryptase levels was investigated in the 8 cases of anaphylactic death; a significant positive correlation was found (r=0.826, p=0.011). Furthermore, chymase was shown to be quite stable in serum. These results showed that measurement of serum chymase levels might be an additional tool for postmortem diagnosis of anaphylaxis.

Aged↗

PubMed2005

Usefulness of a latex agglutination assay for FDP D-dimer to demonstrate the presence of postmortem blood.

D-dimer, a specific fragment resulting from degradation of cross-linked fibrin, is an essential marker for the diagnosis of disseminated intravascular coagulation (DIC). Rapid assay for D-dimer using monoclonal antibody coated-latex particles might be useful for discriminating between postmortem and antemortem blood in bloodstains. We tried to detect D-dimer in nine postmortem blood samples by the rapid latex agglutination assay and to quantify them automatically using the latex photometric immunoassay system. The results showed that all samples were positive and that their amounts of D-dimer were 335-2,800 microg/ml (the normal blood level, <1 microg/ml; the pathogenic blood level with DIC, 1-100 microg/ml). Next, nine stains made of postmortem blood were examined by the rapid latex agglutination assay. The result showed that only one case (D-dimer 335 microg/ml blood) showed weak positive while the others (D-dimer 600-2,800 microg/ml blood) were positive. The present study indicates that the latex agglutination assay for D-dimer can be useful to demonstrate the presence of postmortem blood.

Adolescent↗

PubMed2005

A possible site of superoxide generation in the complex I segment of rat heart mitochondria.

We searched for possible sites of superoxide generation in the complex I segment of the respiratory chain by studying both forward and reverse electron transfer reactions in isolated rat heart mitochondria. Superoxide production was monitored by measuring the release of hydrogen peroxide from mitochondria with a fluorescence spectrophotometer using the Amplex red/horseradish peroxidase system. In the forward electron transfer, a slow superoxide production in the presence of glutamate and malate was enhanced by both rotenone and piericidin A (specific inhibitors at the end of the complex I respiratory chain). Both diphenileneiodonium and ethoxyformic anhydride (inhibitors for respiratory components located upstream of the respiratory chain) inhibited the enhancement by rotenone and piericidin A. In contrast, in reverse electron transfer driven by ATP, both diphenileneiodonium and ethoxyformic anhydride enhanced the superoxide production. Piericidin A also increased superoxide production. Rotenone increased it only in the presence of piericidin A. Our results suggest that the major site of superoxide generation is not flavin, but protein-associated ubisemiquinones which are spin-coupled with iron-sulfur cluster N2.

Animals↗

PubMed2005

[Sudden cardiac death: medico-legal aspects].

Diagnosis of sudden cardiac death (SCD) is the most important forensic practice because of (1) misdiagnosis of extrinsic death as SCD, (2) under-report of unusual (unnatural) death, (3) difficulty in diagnosis by autopsy, histology, and death-scene investigation, (4) difficulty to judge the contribution of accident, violence, psychological stress, over-work, and medical malpractice. Forensic pathologists must precisely diagnose the proximal cause of death and determine the contribution of extrinsic and intrinsic factors, thereby showing fair proof for the legal responsibility of the deceased and concerned party. This article reviews these forensic aspects of SCD with reference cases.

Death, Sudden, Cardiac↗