Biomedical subjects

K Hidaka

Publications and source records attributed to K Hidaka.

At least 37 records · Page 2Linked to original sources

PubMed1999

Chemical studies on antioxidant mechanism of curcuminoid: analysis of radical reaction products from curcumin.

In the course of studies on the antioxidant mechanism of curcumin, its radical reaction was investigated. Curcumin was reacted with radical species, which were generated from the pyrolysis of 2, 2'-azobis(isobutyronitrile) under an oxygen atmosphere, and the reaction products from curcumin were followed by HPLC. The reaction at 70 degrees C gave several products, three of which were structurally identified to be vanillin, ferulic acid, and a dimer of curcumin after their isolation. The dimer was a newly identified compound bearing a dihydrofuran moiety, and its chemical structure was elucidated using spectroscopic analyses, especially 2D NMR techniques. A mechanism for the dimer production is proposed and its relation to curcumin's antioxidant activity discussed. The time course and gel permeation chromatography studies of the reaction were also investigated, and the results indicate that the dimer is a radical-terminated product in the initial stage.

Antioxidants↗

PubMed1999

The morphological changes of exocrine pancreas in chronic pancreatitis.

The following changes were found by either light or electron microscopic observation of the pancreas in spontaneously developed chronic pancreatitis models (WBN/Kob rats, spontaneously hypertensive rats, and rats with common bile-pancreatic duct stones) and in experimental models of chronic pancreatitis (alcoholic pancreatitis, ischemic pancreatitis, and obstructive pancreatitis): 1) the units of lobules, which were constituted by acinar cell deletion, ductular proliferation, and fibrosis; and 2) tortuous or helical ductal channels of pancreatic ducts with periductal fibrosis, which had many crater-like depressions and very long cilia in their inner surface. These are considered to be the results of obstructive pancreatitis, which are caused by the reactions of defensive factors against the increase of pancreatic duct pressure, including the apoptosis of acinar cells, the hyperplasia and hypertrophy of duct cells, a tighter junctional complex of duct cells, and periductal fibrosis.

Animals↗

PubMed1999

Expression of MEF2 genes during human cardiac development.

To better understand the regulatory mechanisms in gene expression of human cardiomyocytes, we studied the expression of MEF2 genes encoding transcription factors during the course of cardiac development. Expression of all four MEF2 transcripts (MEF2A, MEF2B, MEF2C, and MEF2D) were detected in all developmental stage of the human heart, while Mef2b transcripts were down-regulated in mouse heart development. Although none of the MEF2 genes, besides mouse Mef2b, exhibited any remarkable quantitative change in their transcripts, qualitative changes in MEF2 transcripts were found during the course of cardiac development. In particular, MEF2D transcripts showed prominent changes by alternative splicing in the perinatal period. MEF2D transcripts containing the 21-base exon (exon b) were predominantly expressed after birth. At the same time, transcripts of the alpha myosin heavy chain (alphaMHC) gene increased after birth, as the splicing pattern in transcripts of the cardiac troponin T (cTnT) gene changed to decrease the transcripts of cTnT1 after birth. These changes seemed to be correlated with the alternative splicing changes of MEF2 genes, especially MEF2D. The alternative splicing as well as transcriptional regulation in MEF2 genes might be important for regulating the alphaMHC gene and the maturation of cardiomyocytes.

Animals↗

PubMed1999

[Successful combination chemotherapy for a case of small cell carcinoma of the rectum with multiple liver metastasis].

A 69-year-old-man with small cell carcinoma of the rectum and multiple liver metastases was admitted in December 1996. Poorly differentiated adenocarcinoma was preoperatively diagnosed in a biopsy specimen from the rectum. Chemolipiodolization using 50 mg DXR and 6 ml lipiodol was performed for the multiple liver metastases. Ten days later, he underwent rectal amputation including lymph node dissection combined with the implantation of reservoir for hepatic arterial infusion chemotherapy. After operation 5-FU (500 mg, days 1-5) and CDDP (10 mg, days 1-5) were injected for 3 weeks through hepatic arterial route. The metastatic lesions in the liver represented a good response to the chemolipiodolization, though the metastatic tumor in the liver S4 region did not disappear on CT scan. The histological diagnosis of the resected rectum revealed small cell carcinoma so we attempted additional chemotherapy according to the regimen for treatment of small cell lung cancer. ETP + CDDP therapy was performed, in which ETP (100 mg, days 1-3) and CDDP (80 mg, day 1) were intraarterially infused. After three courses of this therapy, he achieved a complete response (CR) for the liver metastasis. Two courses of ETP + CDDP therapy were additionally performed in the outpatient department, and treatment is currently continued by oral administration of ETP (75 mg/day). He has been free of the disease for 16 months with few side effects. The combination therapy of chemolipiodolization and hepatic arterial infusion chemotherapy with ETP and CDDP may assure a good prognosis for multiple liver metastases of small cell rectal cancer.

Aged↗

PubMed1999

[Missense mutations of the butyrylcholinesterase gene in six Japanese patients with low cholinesterasemia: genetic analysis using sera stored in a freezer].

Six serum samples with no detectable butyrylcholinesterase (BCHE) activity had been stored at -70 degrees C for more than 10 years. These sera were used for amplification of BCHE gene using polymerase chain reaction (PCR) and for nucleotide sequence analysis. Five of them demonstrated a C-->T transition at codon 100 (CCA-->TCA), resulting in a Pro-->Ser substitution. The other one was a compound heterozygote as revealed a T-->C transition mutation at codon 203 from TCA (Ser) to CCA (Pro) and G-->C transversion at codon 365 from GGA (Gly) to CGA (Arg). These results showed sera stored in a freezer could be used as a starting material for amplification of genomic DNA when it is not possible to obtain fresh blood samples.

Asian People↗

PubMed1999

[The present situation of home infusion therapy (HIT) and the problems of coordinated service].

Fujisawa Pharmaceutical Co., Ltd. established its home care business division in April, 1995. On the assumption that the patients have the final say in decision making, we aim at smooth operation of home care, adjusted to each patient's needs, which will lead to improvements in quality of life (QOL). Approximately 700 patients took advantage of our pharmacy service between April, 1995 and March, 1999; of them, almost 80 percent had a malignant tumor in the terminal stage and were receiving home parenteral nutrition (HPN). Patient ages ranged from the 50s to the 80s. The number of patients with a malignant disease who take advantage of medical treatment by family doctors or a visiting nurse station is less than that of patients with a benign disease. Following are the problems of coordination for HIT patients: 1) difficulty in understanding the patient's or their family's actual thoughts about home care, 2) insufficient information from the medical staff to the patient or their family for decision making, 3) insufficient coordination in the medical organization, and 4) failure of information exchange between the medical organization's staff and the home-care staff. In order to operate a home care service which can improve QOL, information exchange and cooperation among the members of the home care team is essential.

Aged↗

PubMed1998

Identification of a point mutation associated with a silent phenotype of human serum butyrylcholinesterase--a case of familial cholinesterasemia.

A point mutation which caused a silent phenotype of human serum butyrylcholinesterase (BChE) was identified in the DNA of a 47-year-old Japanese woman who visited our hospital complaining of hypertension. The propositus exhibited an unusually low level of BChE activity, whereas her younger sister and her daughter had intermediate levels of BChE activity and her elder sister a normal level. Immunologically, the amount of BChE protein in the serum of the propositus was normal. DNA sequence analysis of the propositus identified a point mutation at codon 199 (GCA --> GTA), resulting in a Ala --> Val substitution. This alteration is one downstream codon from the catalytic active site (Ser, 198). A family study showed her younger sister and her daughter to have the same mutation.

Blotting, Western↗

PubMed1998

Neurochemical and behavioral characterization of potential antidepressant properties of indeloxazine hydrochloride.

The potential antidepressant properties of indeloxazine hydrochloride were examined in vitro and in vivo. Indeloxazine showed preferential affinity for both [3H] citalopram (Ki: 22.1 nM) and [3H]nisoxetine binding sites (Ki: 18.9 nM) in membranes of the rat cerebral cortex. In microdialysis studies, intraperitoneal injection of indeloxazine (3 and 10 mg/kg) dose-dependently increased the extracellular level of both serotonin and norepinephrine in rat frontal cortex of freely moving rats. Amitriptyline was almost equivalent to indeloxazine in these two assays with the exception of a much weaker effect on extracellular serotonin levels. Spontaneous [3H]serotonin release from rat cortical synaptosomes was significantly enhanced by indeloxazine (10-1000 nM). In behavioral studies, indeloxazine increased the number of wheel rotations in forced swimming tests in both ICR mice (50 mg/kg, p.o.) and SAMP8//YAN, a substrain of senescence-accelerated mouse (20 and 30 mg/kg, p.o.). Indeloxazine (3-10 mg/kg p.o.) also inhibited the incidence of muricide in raphe-lesioned rats. These results suggest that indeloxazine is an inhibitor of serotonin and norepinephrine uptake and has potential antidepressant properties. In addition, the drug-induced enhancement of serotonin release may contribute to its potent effects on the serotonergic system in vivo.

Amitriptyline↗

PubMed1998

Synthesis of (+/-)-cassumunins A and B, new curcuminoid antioxidants having protective activity of the living cell against oxidative damage.

A chemical synthesis of cassumunins A (1) and B (2), natural curcuminoid antioxidants, was developed. The synthesis was started from o-vanillin and after nine reaction steps resulted in 20% and 26% overall yields of 1 and 2, respectively. The synthetic cassumunins showed stronger protective activity than curcumin against oxidative cell death induced by hydrogen peroxide in a rat thymocyte system.

Animals↗

PubMed1998

Release of nitric oxide and expression of constitutive nitric oxide synthase of human endothelial cells: enhancement by a 14-membered ring macrolide.

A 14-membered ring macrolide, erythromycin, acts not only as an antibacterial but also as an anti-inflammatory agent. We have previously reported that erythromycin modulates neutrophil functions and ameliorates neutrophil-induced endothelial cell damage through the action of cyclic AMP-dependent protein kinase (PKA) and nitric oxide (NO). We investigated the effect of erythromycin on human endothelial cell functions. Erythromycin enhanced intracellular calcium ion concentration ([Ca2+]i) of endothelial cells and NO release from endothelial cells. The enhancement of NO release from endothelial cells by erythromycin was abolished by addition of EGTA in the medium and was partially reduced by addition of H-89, an inhibitor of PKA. These results suggest that erythromycin enhances NO release from endothelial cells through the action of PKA and [Ca2+]i. In addition, constitutive NO synthase (cNOS) protein expression of endothelial cells was dose-dependently enhanced by treatment with erythromycin, which might also contribute to the enhancement of NO release from endothelial cells by erythromycin. The effect of erythromycin as an anti-inflammatory agent might be partially mediated through the enhancement of NO release from endothelial cells and the drug might be a useful tool for the investigation of cNOS of endothelial cells.

Anti-Inflammatory Agents↗

PubMed1998

[A new operative technique of posttraumatic syringomyelia: thecoperitoneal shunt].

The authors report a successful case of operative treatment for a patient with a traumatic syringomyelia. A 33-year-old male presented with arm pain and right sided sensory loss due to posttraumatic syringomyelia. Magnetic resonance image showed syringomyelia from the upper cervical cord to the lower thoracic cord. Based on the hypothesis of Ball and Dayan, and Williams, a thecoperitoneal shunt operation was performed. The proximal shunt catheter was placed in the subarachnoid space rostral to the injury level and the distal shunt catheter was introduced percutaneously into the peritoneum. Postoperative radiological studies showed improvement and progressive clinical deterioration stopped. The advantages of this surgery are that it is less invasive to the spinal cord, and that there is a lower shunt malfunction rate because of the use of a D-L catheter which develops less shunt obstruction. Furthermore, we were able to evaluate shunt flow from the valve. In spite of multicystic syrinx, we were easily able to determine the placement of the shunt catheter for this operation. For these reasons, the thecoperitoneal shunt can be placed before further expansion of the syrinx. We think that this method is safer for patients with incomplete cord injury than S-P shunt or S-S shunt.

Adult↗

PubMed1998

[Implementing HPN in an SEP case following long-term CAPD].

BACKGROUND: Sclerosing encapsulating peritonitis (SEP) is one of the most serious complications in continuous ambulatory peritoneal dialysis (CAPD). SEP causes severe bowel obstruction leading to malnutrition and eventually to a high mortality rate. The basic strategy for the care of SEP is to sustain the rest of the bowel, i.e., long-term TPN. We report a case successfully restored to a useful life through HPN. CASE PRESENTATION: The patient is a 26-year-old man, diagnosed as primary nephrotic syndrome in 1980. He had to begin hemodialysis (HD), which was immediately switched to CAPD, due to uremia in 1983. He had been on CAPD for 12 years since that time. He developed SEP as a serious complication of CAPD in July, 1995. CAPD was discontinued, and maintenance HD was started three times a week. Although only liquid diet (such as Renalen and Ensure-Liquid) was allowed as a meal, he often developed intermittent bowel obstruction and repeated hospitalizations were needed to relieve the symptoms. Home parenteral nutrition (HPN) was implemented in May, 1997, in the hope of improving his quality of life. No hospitalization has been needed since then. At present, he is working as an active pharmacist utilizing the HPN system developed by Terumo Co., Ltd. So far a few HPN pump failures have been encountered, but they were promptly handled by the Home Health Care Business Project staff at Terumo Co., Ltd. CONCLUSION: Although further improvements of the present HPN system are necessary, HPN can be a useful tool to effectively manage SEP patients who are suffering from persistent or intermittent bowel obstruction.

Adult↗

PubMed1997

Nonsense mutation in exon 2 of the butyrylcholinesterase gene: a case of familial cholinesterasemia.

A point mutation that causes a silent phenotype for human serum butyrylcholinesterase (BChE) was proved by DNA analyses of a 64-year-old Japanese female who visited the hospital because of a common cold. The propositus and her two siblings showed extremely low BChE activity, but other family members (six individuals) manifested from intermediate to normal values of BChE activity. An immunological method revealed that the propositus and her two siblings showed absence of the BChE protein in serum. DNA sequence analysis of the propositus identified a point mutation at codon 400 (TGC-->TGA), resulting in the production of a stop codon. This alteration exists upstream of the Cys571 of the subunit, which forms a disulfide bridge with the Cys571 of another partner subunit.

Butyrylcholinesterase↗

PubMed1997

Effects of YM-43611, a novel dopamine D2-like receptor antagonist, on immediate early gene expression in the rat forebrain.

The pharmacological characteristics of two benzamides, YM-43611, a potent and selective dopamine D3 and D4 antagonist, and YM-09151-2 (nemonapride), were compared with two reference antipsychotic agents, haloperidol and clozapine, in terms of modification of c-fos and related gene expression in the rat forebrain. After subcutaneous injection of YM-43611 (1 or 5 mg/kg), nemonapride (4 mg/kg), haloperidol (1 mg/kg), or clozapine (25 mg/kg), Fos immunocytochemistry was employed, and the distributions of Fos-like immunoreactive neurons were compared. As was the case for the two reference antipsychotics, the two benzamides enhanced c-Fos immunoreactivity in a number of forebrain regions. Specifically, like clozapine and nemonapride, YM-43611 significantly increased the number of immunoreactive cells in the nucleus accumbens shell and islands of Calleja. In contrast to clozapine and nemonapride, YM-43611 did not increase c-fos expression in the medial prefrontal cortex. Haloperidol and nemonapride elevated the number of positive cells in the striatum and nucleus accumbens core, whereas clozapine and YM-43611 did not. Clozapine increased the number of Fos-like immunoreactive cells in the lateral septal nucleus and the diagonal band nucleus, but YM-43611, nemonapride, and haloperidol did not. The present findings demonstrate that in comparison with three other drugs, YM-43611 has restricted effects on c-fos expression in the rat forebrain and is active primarily in the shell region of the nucleus accumbens and the islands of Calleja. The ability of YM-43611 to block D3 and D4 receptors may contribute to its unique actions on Fos induction.

Animals↗

PubMed1997

Genetic analysis of a Japanese patient with butyrylcholinesterase deficiency.

A patient (64-year-old, male) with familial cholinesterasemia caused by BChE deficiency was studied. DNA sequence analysis of all exons identified a point mutation, an A-->G transition at codon 128, resulting in a Tyr-->Cys substitution. The propositus showed extremely low BChE activity, but his other family members (three individuals) showed from intermediate to normal BChE activity. An immunological method revealed the absence of BChE protein in serum of the propositus. Both PCR primer introduced restriction analysis (PCR-PIRA) and sequence analysis revealed all three family members to be heterozygotes for this mutation.

Asian People↗

PubMed1997

Mouse Mef2b gene: unique member of MEF2 gene family.

The myocyte enhancer factor 2 (MEF2) gene family, which belongs to the MADS [MCM1, agamous, deficiens, serum response factor (SRF)] superfamily, is thought to play an important role in differentiation of myocytes, including cardiomyocytes. To better understand the mouse Mef2 gene family, the mouse Mef2b gene, which was found to be expressed in undifferentiated embryonal cells, was characterized. The Mef2b gene was found to be more than 30 kb in length, consisting of 11 exons. Eight exons correspond to coding regions and the remaining 3 exons for the 5' part are alternatively used. Two internal exons are subject to alternative splicing, resulting in production of four subtypes of mouse MEF2B peptides. Fluorescence in situ hybridization (FISH) and inter-specific backcross analysis identified the Mef2b gene locus. Mef2b gene was expressed in heart or skeletal muscle of early mouse embryo, but not in those of adult mouse. Functionally, mouse MEF2B did not exhibit DNA binding with the MEF2 consensus element in vitro, but did cause transcriptional activation of the MEF2 element, although it was less effective than human MEF2B. Based on these results, mouse MEF2B seems to have a unique character, distinct from other MEF2 family members.

Amino Acid Sequence↗

PubMed1997

Inhibition by erythromycin of human pulmonary artery endothelial cell injury induced by human neutrophils.

Neutrophils are thought to play a key role in tissue injury. We investigated the role of human neutrophils in the induction of injury to the human pulmonary artery endothelial cells and the effect of erythromycin on neutrophil-induced endothelial cell damage. Incubation of unstimulated neutrophils with endothelial cells increased the release of lactate dehydrogenase (LDH) activity and preloaded fura-2 from endothelial cells. When neutrophils were activated by phorbol myristate acetate, the release of LDH and fura-2 was enhanced further. Superoxide dismutase partially inhibited the release of LDH and fura-2 induced by neutrophils, whereas erythromycin markedly inhibited the release of endothelial cell LDH and fura-2 induced by neutrophils. These results suggest that endothelial cell injury is, at least in part, mediated by the action of superoxide and that erythromycin protects against neutrophil-induced endothelial cell injury.

Anti-Bacterial Agents↗

PubMed1997

The role of neutrophil elastase in human pulmonary artery endothelial cell injury.

Neutrophils are thought to play a key role in tissue injury. We investigated the role of human neutrophil-derived elastase in the induction of injury to human pulmonary artery endothelial cells. Incubation of endothelial cells with neutrophils increased the release of lactate dehydrogenase activity, thrombomodulin, and preloaded fura-2 from endothelial cells, indicating that neutrophils induce endothelial cell injury. Attachment alone of neutrophils to endothelial cells appeared to induce activation because elastase release and N-formyl-mentionyl-leucyl-phenylalanine (fMLP)-induced superoxide (O2) production from neutrophils incubated with endothelial cells were greater than from neutrophils only. When endothelial cell were incubated with neutrophils stimulated by fMLP or phorbol myristate acetate, the amount of elastase in the medium and endothelial cell damage was further enhanced. However, when neutrophils were blocked from direct attachment to endothelial cells using a membrane filter, endothelial cell damage was ameliorated, while exogenous neutrophil elastase and medium containing neutrophil-released elastase did not induce endothelial cell injury. An inhibitor of neutrophil elastase, ONO-5046 Na, as well as erythromycin, which reduces neutrophil-derived elastase, dramatically inhibited neutrophil-induced endothelial cell injury. Superoxide dismutase (SOD) partially inhibited injury. Injury was completely inhibited by treatment with a combination of ONO-5046 Na and SOD. These results suggest that attachment of neutrophils to endothelial cells is important for endothelial cell damage and that neutrophil-derived elastase plays an important role in endothelial cell injury in combination with O2. In addition, ONO-5046 Na and erythromycin may be useful in treating diseases worsened by excessive neutrophil activity.

Endothelium, Vascular↗