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Biomedical subjects

K Takayama

Publications and source records attributed to K Takayama.

At least 91 records · Page 5Linked to original sources
PubMed2000

Prognosis of bronchial artery embolization in the management of hemoptysis.

BACKGROUND: Bronchial artery embolization (BAE) is a well-accepted and widely used treatment modality for the management of massive and recurrent hemoptysis. However, few reports have previously investigated the long-term results. OBJECTIVES: To investigate the prognosis of patients with hemoptysis who had undergone BAE. METHODS: Twenty-two patients with hemoptysis underwent BAE. The underlying diseases included bronchiectasis in 9, aspergillosis in 3, chronic bronchitis in 2, idiopathic bronchial bleeding in 4, and other diseases in 4. The follow-up period ranged from 25 to 88 months (median 47 months). RESULTS: After the initial BAE, 11 of 22 (50%) patients had re-bleeding (5 patients with hemoptysis and 6 patients with minor hemosputa). Among them, 1 patient suffered from recurrent massive hemoptysis and died from airway obstruction within 1 month after BAE. In addition, 10 of these 11 (90.9%) patients experienced recurrent airway bleeding within 3 years after BAE. Recurrent cases of hemoptysis were seen in 6 of 22 patients (27.3%) within 3 years and no case recurred later than 3 years after BAE. A recurrence of hemoptysis was frequently seen in patients with either bronchiectasis or pulmonary-bronchial artery (P-B) shunt. Although BAE is an effective treatment for the immediate control of hemoptysis, 5 of the patients experienced recurrent bleeding in the long-term follow-up. CONCLUSIONS: It is important to follow-up such patients until 3 years after initial BAE, especially when either ectatic changes of the bronchi on a CT scan or a P-B shunt on angiographic findings are detected.

Adult↗
PubMed2000

Polycyclic aromatic hydrocarbon carcinogens increase ubiquitination of p21 protein after the stabilization of p53 and the expression of p21.

Polycyclic aromatic hydrocarbon carcinogens (PAHs) and their metabolites have been found to result in a rapid accumulation of p53 gene product in human and mouse cells. However, the induced p53 protein was reported to be transcriptionally inactive. In the present study, the induction of p53 target gene expression after the treatment with either benzo(a)pyrene (B[a]P) or 1-nitropyrene (1-NP) was investigated. A marked induction of messenger RNA (mRNA) expressions of Mdm2, Bax, and p21 was detected in wild-type p53-expressing cells after the treatment with either B[a]P or 1-NP, whereas no significant change in mRNA expression of these genes was observed in p53-negative and mutant cells. 1-NP activated the p21 promoter in a p53-dependent manner. Binding activity of p53 to a p53 consensus sequence increased after the treatment in wild-type p53-expressing cells. Nevertheless, the induced mRNA levels of the p21 did not result in a proportional p21 protein increase, indicating the possibility of post-transcriptional regulation of the protein. With the addition of MG-132, a proteasome inhibitor, to B[a]P or 1-NP treatments, both p21 and p53 protein levels were increased; however, the increase in p21 protein levels was significantly larger than the increase in p53 protein levels. PAHs treatment increased the level of ubiquitinated p21. These results suggest that the p21 product is degraded by the ubiquitin-proteasome system. We conclude that PAHs-induced p53 protein is transcriptionally active.

Benzo(a)pyrene↗
PubMed2000

High entrapment of insulin and bovine serum albumin into neutral and positively-charged liposomes by the remote loading method.

Remote loading of insulin and bovine serum albumin (BSA) into neutral or positively-charged liposomes by incubation under a transmembrane pH gradient or non-pH gradient was investigated. Trapping efficiencies in several incubation conditions were compared with those of the conventional reverse-phase evaporation vesicle method (c-REV method). For neutral liposomes, insulin could not be effectively loaded into the liposomes by incubation, regardless of the incubation conditions. The trapping efficiency of insulin into positively-charged liposomes was higher than that of neutral liposomes, especially by the pH-gradient method. Insulin could be loaded into positively-charged liposomes about twofold more efficiently than by the pH-gradient method, compared with the c-REV method. Insulin distributed more on the surface of liposomes by the pH-gradient method than by the c-REV method. BSA showed significantly higher affinity to positively-charged liposomes than to neutral ones by various methods. However, the transmembrane pH-gradient method did not increase BSA loading into liposomes, compared with the c-REV and the non-pH-gradient methods. Our results suggest that the pH-gradient method, combining electrostatic interactions, may be useful for preparation of liposomal insulin and that the high hydrophobicity of BSA may not increase the remote loading of BSA into liposomes by the pH-gradient method.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

Electron spin resonance studies of dipalmitoylphosphatidylcholine liposomes containing soybean-derived sterylglucoside.

The effects of soybean-derived sterylglucoside (SG) on the fluidity of liposomal membrane composed of dipalmitoylphosphatidylcholine (DPPC) were investigated compared with those of soybean-derived sterol (SS) and cholesterol (Ch) using an electron spin resonance spectrometer. Three kinds of liposomes were prepared in the molar ratio of DPPC/X=7/4, where X is SS, Ch or SG. The fluidity close to the polar head groups increased with an increase of temperature in the DPPC membrane containing SS, Ch and SG in the range 35 to 45 degrees C. Those near the hydrophobic end changed with an increase in temperature in liposomes containing SS, Ch and SG, which had a fluidizing effect on the DPPC membrane below the transition temperature (Tm, 41.9 degrees C) and a condensing effect over the Tm. The fluidizing effects of these compounds around 37 degrees C near the polar head group and the hydrophobic end increased in the following order: Ch < SG < or = SS and SS < Ch < SG, respectively. SG increased the fluidity of liposomal membrane dramatically above the Tm (35.4 degrees C). These results suggest that the high fluidity close to the hydrophobic end of the liposomal membranes around 37 degrees C, the decrease of Tm, and the sigmoidal nature of fluidity vs. temperature are important factors in the effectiveness of liposomes containing SG as a carrier of drugs.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

Inducible nitric oxide-mediated myocardial apoptosis contributes to graft failure during acute cardiac allograft rejection in mice.

The mechanism through which nitric oxide (NO) mediates cardiac myocyte death during acute cardiac rejection has not been fully delineated. We sought to determine whether NO promotes myocardial apoptosis and contributes to graft failure during acute cardiac rejection in a murine model. Heterotopic cardiac transplantation was performed from Balb/c (H-2d) to C3H/He mice (H-2k). Recipients were treated with aminoguanidine (AG) at 400 mg/kg every day after surgery. As references, we used isografts in Balb/c mice with and without AG treatment (400 mg/kg/day). Graft survival, histological changes and serum NO levels were assessed. Intra-graft apoptosis was evaluated using a DNA fragmentation detection assay (TUNEL method) and DNA laddering. Significant prolongation of graft survival was observed in allografts treated with AG in comparison with nontreated allografts. Serum NO levels, which peaked on day 7 in nontreated allografts, were significantly decreased in AG-treated allografts. AG treatment decreased the number of apoptotic cells and lowered the ratio of the apoptotic cardiac myocytes in contrast to that of the apoptotic infiltrating cells. DNA laddering was clearly detected in nontreated allografts but was suppressed in AG-treated allografts. Inhibition of NO production by AG prolonged murine cardiac allograft survival. The decrease in intra-graft apoptotic activity paralleled histological improvement. Cardiac myocyte death which occurs through an apoptotic process mediated by NO contributes to graft failure during acute cardiac rejection.

Animals↗
PubMed2000

Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance.

Conversion of C(19) steroids to estrogens is catalyzed by aromatase in human ovary, placenta and extraglandular tissues such as adipose tissue, skin and the brain. Aromatase activity is not detectable in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis and is stimulated by prostaglandin E(2) (PGE(2)).( )This results in local production of estrogen, which induces PGE(2) formation and establishes a positive feedback cycle. Another abnormality in endometriosis, i.e. deficient hydroxysteroid dehydrogenase (17beta-HSD) type 2 expression, impairs the inactivation of estradiol to estrone. These molecular aberrations collectively favor accumulation of increasing quantities of estradiol and PGE(2 )in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of postmenopausal endometriosis using an aromatase inhibitor.

Anastrozole↗
PubMed2000

[Sick sinus syndrome (SSS) after induction of anesthesia in a patient with increased intracranial pressure and ischemic heart disease].

An 84-year-old male with increased intracranial pressure (ICP) and ischemic heart disease was scheduled to undergo brain tumor resection. After induction of anesthesia using midazolam, fentanyl and vecuronium, sinus bradycardia, junctional rhythm and escape-capture bigeminy were observed. In spite of intravenous administration of lidocaine and atropine, the bigeminy did not disappear. As he awoke from anesthesia, his cardiac rhythm changed from a bigeminal to a regular sinus rhythm. After extubation, sinus arrest, which continued for up to 4.8 seconds, appeared frequently. A temporary pacing catheter was inserted and ventricular pacing was started (mode VVI rate 50 min-1). Four days later, the patient was again scheduled to undergo brain tumor resection. After induction of anesthesia with the same drugs as used before, his cardiac rhythm gradually became bradycardic, and a complete pacing rhythm was observed throughout the surgical procedure. After the operation had been completed, his cardiac rhythm changed to a regular sinus rhythm. In addition to degenerative and ischemic changes in the SA node, an increase in ICP secondary to a brain tumor is thought to have induced sick sinus syndrome after the induction of anesthesia.

Aged↗
PubMed2000

[Gene therapy for lung cancer treatment].

Gene therapy is a promising strategy for cancer treatment. The strategy is categorized to some fields based on the anti-cancer mechanism. p53 gene therapy and antisense therapy exert the cytotoxic effect on cancer cells by apoptosis induction. In suicide gene therapy, expressed suicide gene product kills the cancer cells in combination with prodrug which metabolite is cytotoxic agent. Oncolytic virus replicates in the tumor selectively and destroys the cancer cells. Immunogene therapy potentiates the antigenicity of cancer cells or activate the immune effector cells. In antiangiogenesis gene therapy, neovascularization is inhibited with antiangiogenic molecule gene such as angiostatin. On the other hand, bone marrow stem cells are protected from high dose anti-cancer agents by the transfer of multi-drug resistant gene.

Cytokines↗
PubMed2000

Gene transfer of a soluble receptor of VEGF inhibits the growth of experimental eyelid malignant melanoma.

PURPOSE: To determine the effect of adenovirus-mediated gene transfer of a soluble receptor of vascular endothelial growth factor (VEGF) on the growth of experimental eyelid malignant melanoma. METHODS: An adenovirus vector encoding a soluble VEGF receptor/flt-1 (Adflt-ExR) was constructed. The bovine retinal endothelial cells (ECs) were incubated in a culture medium of 293E1 cells infected by means of an adenovirus vector or uninfected (control), which contained human recombinant VEGF, and the [3H]thymidine uptake was tested. The experimental eyelid malignant melanoma was induced by the injection of B16 melanoma cells (4 x 10(6) cells) into the right upper eyelid of BALB/c nu/nu mice, and the size of the tumor was recorded for 3 weeks after tumor cell injection. The effect of Adflt-ExR was examined in three ways. Model 1: B16 cells were infected by Adflt-ExR beforehand (at a multiplicity of infection [MOI] of 10) and injected into the eyelid. Model 2: Adflt-ExR was injected into pre-established B16 cell-induced eyelid malignant melanoma. Model 3: Adflt-ExR was injected into the femoral muscle of mice before B16 cell injection into the eyelid, and the remote effect was evaluated. An adenovirus vector bearing the LacZ gene (AdLacZ) or phosphate-buffered saline was used as a control. The amount of VEGF and the flt-ExR protein was measured by sandwich enzyme-linked immunosorbent assay (ELISA). Vascularization was evaluated by counting the number and the size of the vessels. RESULTS: The supernatant of Adflt-ExR-transfected cells clearly inhibited VEGF-induced bovine retinal EC proliferation in vitro. In models 1 and 2, the tumor growth in Adflt-ExR-treated mice was significantly lower than that of controls (P < 0.05). In model 3, no significant difference was found (P = 0.14). The molar ratio of VEGF/flt-ExR protein was clearly low in the tumors of Adflt-ExR-treated mice in models 1 and 2 (P < 0.01) but not in model 3 (P > 0.05). In vessel density, the tumors in Adflt-ExR-treated mice had fewer vessels than tumors in control animals in models 1 and 2 (P < 0.05). CONCLUSIONS: Adenovirus-mediated gene transfer of a soluble form of VEGF receptor (flt-1) gene inhibited the growth of the experimental eyelid malignant melanoma. This method may be useful as an antiangiogenic therapy for eyelid malignant melanoma.

Adenoviridae↗
PubMed2000

A novel phosphodiesterase type 4 inhibitor, YM976 (4-(3-chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2(1H)-one), with little emetogenic activity.

We synthesized a novel phosphodiesterase type 4 (PDE4) inhibitor, YM976, that is structurally different from the other PDE4 inhibitors like rolipram. In the present study, the pharmacological profile of YM976 was investigated. YM976 exhibited a strong and competitive inhibition against PDE4 purified from human peripheral leukocytes with an IC(50) of 2.2 nM. IC(50) values of rolipram and RP73401 were 820 and 0.43 nM, respectively. Test compounds had no effects on the other PDE isozymes, PDE1, -2, -3, and -5. YM976 potentiated prostaglandin E(2)-induced cAMP accumulation in a human mononuclear cell line, U937, and inhibited tumor necrosis factor-alpha production from human peripheral blood mononuclear cells stimulated by lipopolysaccharide. Anti-inflammatory activities of PDE4 inhibitors were compared in rat carrageenan-induced pleurisy models. YM976, rolipram, and RP73401 inhibited the cell infiltration into the pleural cavity with oral ED(30) values of 9.1, 10, and 7.4 mg/kg, respectively. YM976 produced no emesis up to 10 mg/kg, whereas rolipram and RP73401 induced emesis at oral doses of 3 mg/kg. To evidence the dissociation of anti-inflammatory activity from emesis, the anti-inflammatory effect of YM976 was examined in ferrets. YM976 dose dependently reduced carrageenan-induced leukocyte infiltration at the doses of 1, 3, and 10 mg/kg, p.o. On the other hand, rolipram failed to show obvious inhibition at doses that do not induce emesis. In conclusion, YM976 is a novel and orally active PDE4 inhibitor and possesses a good separation of emetogenicity from anti-inflammatory activity.

Animals↗
PubMed2000

[A case of distal posterior cerebral artery aneurysm associated with occlusion of the internal carotid artery].

Hemodynamic stress is considered one of the most important factors in the growth of cerebral aneurysms. The authors report a rare case of cerebral aneurysm located at the distal posterior cerebral artery (PCA) in which collateral circulation developed due to occlusion of the internal carotid artery (ICA). A 73-year-old male was admitted to our hospital with a sudden headache and nausea. Computerized tomography (CT) revealed an intracerebral hematoma in the right parieto-occipital lobe and the acute subdural hematoma in both the cerebral interhemispheric fissure and the convexity. Moreover, angiography revealed a saccular aneurysm at the P4 portion of the PCA. The right ICA was occluded at the cervical portion and collateral circulation which had developed in the PCA was extended to the region of the right middle cerebral artery. The aneurysm was clipped 15 days after admission without new neurological complications. This case demonstrates that increased hemodynamic stress plays a role in the growth and rupture of cerebral aneurysm.

Aged↗
PubMed2000

[Lung cancer risk and genetic polymorphism at the glutathione S-transferase P1 locus in male Japanese].

The glutathione S-transferases (GSTs) are widely expressed in mammalian tissues and involved in Phase II detoxification reactions. The GSTs form a supergene family consisting of four distinct families, named alpha (GSTA), mu (GSTM) theta (GSTT) and pi (GSTP). Several of the GST genes are polymorphic in humans and are currently being investigated as possible cancer-risk modifiers. Among the GST genes, we examined GSTP1 polymorphism in exon 5 among male lung cancer patients (n = 86, male Japanese) and male healthy controls (n = 80, male Japanese) by restriction fragment length polymorphism-polymerase chain reaction method. The cancer patients showed frequency of the GSTP1 mutated genotype (individuals having at least one mutant allele, 29.1%) very similar to that of the control subjects (28.8%). After adjusting for smoking status, no association was found between the GSTP1 mutated genotype and lung cancer risk (odds ratio: 0.95; 95% confidence interval: 0.48-1.90). When study subjects were divided into two subgroups based on smoking status, the GSTP1 mutated genotype was not associated with an increased risk of lung cancer among smokers and non-smokers. These results suggest that GSTP1 polymorphism in exon 5 alone may not increase the risk of lung cancer in male Japanese.

Adult↗
PubMed2000

[Anesthetic management of MIDCAB in a patient with Wolff-Parkinson-White syndrome].

We experienced the anesthetic management of a minimally invasive direct coronary artery bypass (MIDCAB) in a patient with Wolff-Parkinson-White (WPW) syndrome. A 55-year-old male had chest pain on effort and was diagnosed as having stenosis of the left coronary artery (#6). He was scheduled to undergo MIDCAB. Anesthesia was induced with midazolam 5 mg, fentanyl 300 micrograms, and vecuronium 10 mg and maintained with air-oxygen, propofol, and fentanyl (27 micrograms.kg-1). Diltiazem was continuously infused at a rate of 0.5-1.5 micrograms.kg-1.min-1 throughout the surgery. The hemodynamic parameters were maintained stable and paroxysmal supraventricular tachycardia was not observed during the procedure. We conclude that the administration of propofol and a medium dose of fentanyl is useful for the anesthetic management of MIDCAB in patients with WPW syndrome and that intraoperative administration of diltiazem might be needed to avoid paroxysmal supraventricular tachycardia.

Anesthesia, Intravenous↗
PubMed1999

Benzo[a]pyrene activates the human p53 gene through induction of nuclear factor kappaB activity.

p53 is known to be recruited in response to DNA-damaging genotoxic stress and plays an important role in maintaining the integrity of the genome. In the present study, the effect of a potent lung cancer carcinogen, benzo[a]pyrene (B[a]P) on p53 expression was investigated. We showed that exposure of A549 and NIH 3T3 cells to B[a]P resulted in an increase in p53 mRNA levels and in p53 promoter activation, indicating that B[a]P-induced p53 expression is partly regulated at the transcriptional level. The p53 promoter region which extends from -58 to -43, overlapping the kappaB motif, is essential for both the p53 basal promoter activity and p53 promoter activation induced by B[a]P. Nuclear factor kappaB (NF-kappaB) proteins have been revealed to be activated in B[a]P-induced p53 expression. Activated NF-kappaB complexes were shown to contain predominantly p50 and p65 subunit components in A549 cells and p65 subunit in NIH 3T3 cells. In addition, the overexpression of IkappaBalpha completely inhibited NF-kappaB activation, p53 promoter transactivation and the stimulatory effect on p53 transcription induced by B[a]P. We therefore conclude that B[a]P transcriptionally activates the human p53 gene through the induction of NF-kappaB activity.

3T3 Cells↗
PubMed1999

Formula optimization based on artificial neural networks in transdermal drug delivery.

The promoting effect of O-ethylmenthol (MET) on the percutaneous absorption of ketoprofen from alcoholic hydrogels was evaluated in rats in vitro and in vivo. Furthermore, a novel simultaneous optimization technique incorporating an artificial neural network (ANN) was applied to a design of a ketoprofen hydrogel containing MET. When a small quantity of MET (0.25-0.5%) was added to the hydrogels, the permeation of ketoprofen increased remarkably, compared with the control. On the other hand, little change in permeation was observed when small amounts of menthol were used (<1%), and at least 2% menthol was required to obtain a promoting efficiency comparable with 0.25% MET. The partitioning of ketoprofen from the hydrogel to the skin was improved by the addition of a small amount of MET, whereas the diffusivity of the drug was enhanced at higher concentration of MET (0.5-1%). For the optimization study, the amount of ethanol and MET were selected as causal factors. A rate of penetration (R(p)) and lag time (t(L)) and total irritation score (TIS) were selected as response variables. A set of causal factors and response variables was used as tutorial data for ANN and fed into a computer. Nonlinear relationships between the causal factors and the response variables were represented well with the response surface predicted by ANN. The optimization of the ketoprofen hydrogel was performed according to the generalized distance function method. The observed results of R(p) and TIS, which had a lot of influence on the effectiveness and safety, coincided well the predictions.

Animals↗
PubMed1999

Uptake and release of budesonide from mucoadhesive, pH-sensitive copolymers and their application to nasal delivery.

Microparticles of novel, bioadhesive graft copolymers of polymethacrylic acid and polyethylene glycol (P(MAA-g-EG)) were prepared. The aims of this study were to investigate the uptake and release kinetics of budesonide from P(MAA-g-EG) in vitro as well as the pharmacokinetics following nasal administration of the polymer contained budesonide. The loading of budesonide into the pH-sensitive polymers was examined using various ethanol solutions. Ethanol was required for drug solubilization but hindered hydrogel swelling at pH 7.2. Maximum loading of the drug in the polymer was obtained using 25% ethanol solutions. The release of budesonide from the polymer swollen in 25% ethanol solutions obeyed classical Fickian release behavior after an initial rapid drug burst. For nasal administration of budesonide-containing P(MAA-g-EG) the plasma concentration of budesonide was kept constant following a peak concentration of the drug approximately 45 min after administration.

Adhesiveness↗
PubMed1999

Influence of non-ionic surfactants, pH and propylene glycol on percutaneous absorption of piroxicam from cataplasm.

The influence of pH in the formulation, ethylene oxide chain length of polyoxyethylene (POE) non-ionic surfactants and addition of propylene glycol (PG) on percutaneous absorption of piroxicam (Px) from cataplasm was investigated in guinea-pig in vivo. The area under the plasma concentration of Px curve until 8 h after the application (AUC(0-8)) increased with increasing the cataplasm base pH up to 6.5 and then plateaued from pH 6.5 to 7.2. Px solubility in water increased markedly with increasing pH from pH 6 as Px is a weak acid and its pK(a) is 5.3. The ionic form of Px in the cataplasm was suspected to contribute to the percutaneous absorption of Px. The percutaneous absorption of Px from the cataplasms containing 5% of POE non-ionic surfactants with various POE lengths were examined. The parabolic relation between the Px absorption and the POE length was observed. POE length from 5 to 15 enhanced percutaneous absorption to a greater extent. An attempt was also made to examine the influence of the addition of PG to the formulation containing POE (9) lauryl ether. The addition of 20% PG to the formulation significantly increased the Px concentration in plasma, compared to 0, 5, 10 and 15% PG. Skin and cutaneous muscle concentrations significantly increased by addition of 20% PG, compared to those by 0% PG but not in deeper muscle.

Administration, Topical↗