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Biomedical subjects

K Takeuchi

Publications and source records attributed to K Takeuchi.

At least 469 records · Page 26Linked to original sources
PubMed1998

Diastolic dysfunction coincides with early mild transplant rejection: in situ measurements in a heterotopic rat heart transplant model.

BACKGROUND: Diastolic dysfunction seen in early clinical transplant rejection has been difficult to demonstrate in experimental rodent models because of the inability to make sensitive in situ measurements of systolic and diastolic functions. We have developed a heterotopic heart transplant model with Fisher 344 and ACI rats (without immunosuppression), where in situ measurements of diastolic and systolic functions were made sequentially (daily) by use of an implanted left ventricular balloon. METHODS: Syngeneic and allogeneic heterotopic heart transplants were performed. In situ function was determined by varying balloon volume to measure the developed pressure, the rates of pressure rise (+dp/dt) and pressure fall (-dp/dt), diastolic pressure-volume relationship, and the time constant of diastolic relaxation (tau). These results were compared with function measurements in transplanted hearts that were excised and perfused in a Langendorff mode (ex vivo) during the same posttransplantation period. RESULTS: Histologic examination revealed that at day 3 after transplantation, allografts showed mild lymphocytic infiltration indicative of mild or early rejection, and by day 5, there was severe rejection with myocyte necrosis. By day 3, the slope of the diastolic pressure-volume relationship (ie, left ventricular stiffness) was significantly higher in allografts as compared with isografts (436 +/- 96 vs 177 +/- 26 mm Hg/mL, p < .05). Similarly, tau was significantly longer in allografts by day 3 after transplantation. Developed pressure and +dp/dt became significantly lower in allografts beginning on day 6. Function measurements made in the isolated perfused ex vivo hearts yielded the same results at day 3 after transplantation as the in situ group of hearts. CONCLUSION: Using a chronically implanted left ventricular balloon, we have developed a heterotopic heart transplant model where sensitive measurements of systolic and diastolic functions can be made. With this preparation, the early changes in the diastolic dysfunction seen clinically can be reproducibly detected. Thus this model may be useful to study mechanisms and interventions during early transplant rejection.

Animals↗
PubMed1998

[Pulmonary actinomycosis with "balls-in-a hole" appearance diagnosed by examination of bronchial lavage fluid].

A 49-year-old man was referred to our hospital because of abnormal chest X-ray findings. Chest X-ray films showed infiltrative opacities in the right lung, and histological findings of a transbronchial biopsy specimen showed non-specific inflammation. The patient was treated with Ofloxacin for one month. After the treatment, chest X-ray films showed that the infiltrative opacities in the right upper lobe had decreased, but that opacities in the right lower lobe had increased, with an air meniscus sign. A chest computed tomography scan at the same time revealed that the remaining opacities contained multiple mass-like lesions within a cavity in the right S6, appearing as "balls in a hole". One year after the first visit, the patient visited the hospital again because of cough and sputum. A chest X-ray film showed that the size of the cavity in the right lower lobe had increased. The histological findings from a fresh transbronchial biopsy specimen revealed a non-specific inflammation again; however, black clots obtained from bronchial lavage fluid after biopsy were histologically identified as sulfur granules, a classic pathological indication of actinomycosis. This confirmed the diagnosis of pulmonary actinomycosis. The patient was treated with penicillin, and the opacities in the right lower lobe subsided.

Actinomycosis↗
PubMed1998

[Japanese cedar pollinosis in children in our allergy clinic].

Recently, it is pointed out that the incidence of Japanese cedar pollinosis has increased in children. We studied on the rate of sensitization and the onset of the disease in children under sixteen who visited allergy clinic in the Department of Otorhinolaryngology in Mie University Hospital. The percentage of positive rate of skin test and IgE antibodies of house dust mite was about 80 to 90% in 1981, 1991, and 1996. However, the percentage of positive rate of skin test and IgE antibodies of Japanese cedar pollen was 43% and 26%, respectively in 1981, but both increased to 58% in 1996. Most of Japanese cedar pollinosis patients also had house dust mite allergy. Among 115 pediatric patients who visited our allergy clinics in the past seven years, 32.2% were allergic to house dust mite alone, 8.6% were allergic to Japanese cedar pollen alone, 40.9% were allergic to both, and 6.1% were allergic to house dust mite, Japanese cedar pollen, and orchard grass pollen. 68% of the total 115 patients were boys, but significantly more girls had the pollinosis. 17.4% of those who are sensitized to the pollen were asymptomatic during the pollen season. Thus, it was confirmed that the rate of children sensitized to the pollen has apparently increased for the past twenty years. We should take care of those children who are sensitized to the pollen but asymptomatic during the pollen season.

Adolescent↗
PubMed1997

Possible role of P-450 metabolite of arachidonic acid in vasodilator mechanism of angiotensin II type 2 receptor in the isolated microperfused rabbit afferent arteriole.

Although angiotensin II type 2 (AT2) receptor has recently been cloned, its functional role is not well understood. We tested the hypothesis that selective activation of AT2 receptor causes vasodilation in the preglomerular afferent arteriole (Af-Art), a vascular segment that accounts for most of the preglomerular resistance. We microperfused rabbit Af-Arts at 60 mmHg in vitro, and examined the effect of angiotensin II (Ang II; 10(-11)-10(-8) M) on the luminal diameter in the presence or absence of the Ang II type 1 receptor antagonist CV11974 (CV; 10(-8) M). Ang II was added to both the bath and lumen of preconstricted Af-Arts. Ang II further constricted Af-Arts without CV (by 74+/-7% over the preconstricted level at 10(-8) M; P < 0.01, n = 7). In contrast, in the presence of CV, Ang II caused dose-dependent dilation; Ang II at 10(-8) M increased the diameter by 29+/-2% (n = 7, P < 0.01). This dilation was completely abolished by pretreatment with an AT2 receptor antagonist PD123319 (10(-7) M, n = 6), suggesting that activation of AT2 receptor causes vasodilation in Af-Arts. The dilation was unaffected by inhibiting either nitric oxide synthase (n = 7) or cyclooxygenase (n = 7), however, it was abolished by either disrupting the endothelium (n = 10) or inhibiting the cytochrome P-450 pathway, particularly the synthesis of epoxyeicosatrienoic acids (EETs, n = 7). These results suggest that in the Af-Art activation of the AT2 receptor may cause endothelium-dependent vasodilation via a cytochrome P-450 pathway, possibly by EETs.

8,11,14-Eicosatrienoic Acid↗
PubMed1997

Mechanisms underlying apoptosis induced by combination of 5-fluorouracil and interferon-gamma.

Several investigators have reported on the clinical effects of 5-fluorouracil (5-FU) or the combination of 5-FU plus interferon-gamma (IFN-gamma) on patients with advanced colorectal carcinoma. It has also been reported that apoptosis induced by 5-FU is due to the effects on DNA synthesis and functional RNA synthesis. In the present study, we examine the biological mechanisms underlying 5-FU or the combination of 5-FU plus IFN-gamma, using the colorectal carcinoma cell line, COLO 201, 5-FU and IFN-gamma independently or additively induced apoptosis in COLO 201 in a dose- and time-dependent manner, which was correlated with the down-regulation of Bcl-2 and the up-regulation of Bax. An interleukin-1 beta-converting enzyme (ICE)-like protease inhibitor (but not an ICE-inhibitor) blocked apoptosis induced by only 5-FU. These results suggest that 5-FU has the capacity to induce apoptosis in COLO 201, resulting from the up-regulation of Bax; the apoptosis-inducing signal of 5-FU seems to be different from that of IFN-gamma. Thereby, 5-FU and IFN-gamma have additional effects on the induction of apoptosis. This finding provides an experimental basis for clinical therapy using 5-FU and/or IFN-gamma for colorectal cancer.

Adenocarcinoma↗
PubMed1997

ERM (ezrin/radixin/moesin)-based molecular mechanism of microvillar breakdown at an early stage of apoptosis.

Breakdown of microvilli is a common early event in various types of apoptosis, but its molecular mechanism and implications remain unclear. ERM (ezrin/radixin/moesin) proteins are ubiquitously expressed microvillar proteins that are activated in the cytoplasm, translocate to the plasma membrane, and function as general actin filament/plasma membrane cross-linkers to form microvilli. Immunofluorescence microscopic and biochemical analyses revealed that, at the early phase of Fas ligand (FasL)-induced apoptosis in L cells expressing Fas (LHF), ERM proteins translocate from the plasma membranes of microvilli to the cytoplasm concomitant with dephosphorylation. When the FasL-induced dephosphorylation of ERM proteins was suppressed by calyculin A, a serine/threonine protein phosphatase inhibitor, the cytoplasmic translocation of ERM proteins was blocked. The interleukin-1beta-converting enzyme (ICE) protease inhibitors suppressed the dephosphorylation as well as the cytoplasmic translocation of ERM proteins. These findings indicate that during FasL-induced apoptosis, the ICE protease cascade was first activated, and then ERM proteins were dephosphorylated followed by their cytoplasmic translocation, i.e., microvillar breakdown. Next, to examine the subsequent events in microvillar breakdown, we prepared DiO-labeled single-layered plasma membranes with the cytoplasmic surface freely exposed from FasL-treated or nontreated LHF cells. On single-layered plasma membranes from nontreated cells, ERM proteins and actin filaments were densely detected, whereas those from FasL-treated cells were free from ERM proteins or actin filaments. We thus concluded that the cytoplasmic translocation of ERM proteins is responsible for the microvillar breakdown at an early phase of apoptosis and that the depletion of ERM proteins from plasma membranes results in the gross dissociation of actin-based cytoskeleton from plasma membranes. The physiological relevance of this ERM protein-based microvillar breakdown in apoptosis will be discussed.

Animals↗
PubMed1997

Histological study of urinary bladder transplantation in rats.

Patients who require cystectomy are usually treated with an ileal conduit or intestinal neobladder for urinary control. In some of them, however, the bowel segment cannot be used because of previous abdominal surgery or radiation treatment. Bladder transplantation from cadavers may be beneficial to these patients, if possible. To obtain basic knowledge about bladder transplantation, we developed an animal model of whole bladder transplantation in rats. Male Lewis rats weighing 270-320 g were used as both donors and recipients. Of the 23 recipients, 12 (52.2%) survived 7 days or longer after surgery. At 1 week after transplantation, the bladder showed loss of transitional epithelium and remarkable cellular infiltration. In the bladder at 5 weeks after transplantation, the transitional epithelium regenerated markedly and submucosal cellular infiltration was much improved. Regeneration of some smooth muscle cells was also noted. At 6 months after transplantation, the nerve fibers were recognized in the bladder and the volume of the transplanted bladder was well preserved (1.0-1.3 ml). This article describes an animal model of whole bladder transplantation in the rat which we produced and the results of our study. Because a large number of pure-bred animals can easily be used, we believe our rat model is very useful for basic studies of bladder transplantation.

Animals↗
PubMed1997

Sequence analysis of a 685-kb genomic region on chromosome 3p22-p21.3 that is homozygously deleted in a lung carcinoma cell line.

Frequent chromosomal aberrations and/or losses of heterozygosity involving the short arm of chromosome 3 in carcinomas of the lung, kidney and other tissues imply that multiple putative tumor suppressor genes may be present on this chromosomal arm. To search for one of these genes, we determined DNA sequences in the genomic region at 3p22-21.3 where we had previously detected a homozygous deletion in a lung cancer cell line. The DNA sequence results of an about 685-kb region indicated that the size of the homozygously deleted segment was 638,489 bp, in which we identified only four genes including the integrin alpha RLC and the trans-Golgi p230 genes, both reported previously. The predicted amino acid sequences of one of the two novel genes showed high homology to villin, a human cytoskeleton protein; those of the other gene, termed HYA22, revealed significant homology to YA22, a hypothetical protein predicted from DNA sequences of Schizosaccharomyces pombe. The computer programs HEXON or GRAIL were able to predict three-fourths of the exons; the smallest exon predicted by either program was 46 base pairs. Repetitive sequences contained in the genomic region included 151 copies of the Alu sequence (1 copy/every 4.5 kb), 19 copies of the L1 sequence (1 copy/every 36 kb), and 10 copies of the THE sequence.

Amino Acid Sequence↗
PubMed1997

Coronary artery stenting with high-pressure post-dilation followed by adjunctive thrombolysis after failed coronary angioplasty for acute myocardial infarction: report of three cases.

We successfully implanted coronary stents into refractory reoccluded lesions after failed coronary angioplasty in three patients with acute myocardial infarction (AMI). Lesion location was the proximal left anterior descending coronary artery in two patients and the dominant right coronary artery in one patient. The reference diameters of the lesions were 3.64, 3.33, and 3.50 mm, respectively. A stent with a luminal diameter of 3.0 mm was implanted in all patients. Poststenting dilation of the stent was performed at high pressure (18 atm), and urokinase was administered immediately thereafter. Heparin was administered for 24 h with maintenance of activated coagulation time within 180-200 s. Warfarin was then administered to keep the international normalized ratio within 2.5-3.5. Luminal diameters immediately after stenting were 3.14, 2.89, and 3.26 mm, and those at 1 month after stenting were 3.09, 2.81, and 3.12 mm, respectively, indicating good patency. Our experience in these cases suggests that coronary stenting can be applied after unsuccessful coronary angioplasty in selected patients with AMI. The present report includes informative reference data on diameter, postdilation, adjunctive thrombolytic agent administration, and adequate anticoagulation therapy in coronary stenting in this acute application.

Aged↗
PubMed1997

Differences in expression of sarcoplasmic reticulum Ca2+-ATPase and Na+-Ca2+ exchanger genes between adjacent and remote noninfarcted myocardium after myocardial infarction.

Although cardiac failure can develop over time after myocardial infarction, the mechanism responsible for this is still unknown. The change of intracellular Ca2+ transport protein, such as sarcoplasmic reticulum (SR) Ca2+-ATPase (SR-Ca2+), Na+-Ca2+ exchanger (Na+-Ca2+), or cardiac phenotypic modulation of contractile protein in noninfarcted myocardium may have a important role. However, the time course in gene expression of sarcoplasmic reticulum (SR) Ca2+-ATPase (SR-Ca2+), Na+-Ca2+ exchanger (Na+-Ca2+), and contractile protein in the adjacent and remote noninfarcted myocardium after myocardial infarction has not been examined. At 1, 3 weeks and 3 months after myocardial infarction, hemodynamics were measured and mRNA of the left ventricle was analyzed. Left ventricular end-diastolic volume and weight increased both with time. Ascites became apparent at 3 months after infarction. SR-Ca2+ mRNA levels in the adjacent noninfarcted myocardium were 0.7- (P<0.01), 0.9- (N.S.), and 0.7-fold (P<0.01) of control, and Na+-Ca2+ mRNA levels were 2.1- (P<0.01), 1.4- (P<0.01), and 0.8-fold (P<0.01) of control, at 1, 3 weeks and 3 months after infarction, respectively. beta-Myosin heavy chain (MHC) mRNA was increased to 2.1- (P<0.01), 1.5- (P<0.01), and 1.4-fold (P<0.01), and alpha-skeletal actin was increased to 2.4- (P<0.01), 3.8- (P<0.01), and 1.6-fold (P<0.01) control levels, at 1 week, 3 weeks and 3 months, respectively. In contrast, alpha-MHC mRNA level was decreased at 1 week and 3 months after infarction. alpha-cardiac actin mRNA level did not change over time after infarction. In the remote non-infarcted myocardium, beta-MHC, alpha-skeletal actin, and Na+-Ca2+ mRNA levels were increased, but SR-Ca2+, alpha-MHC, and alpha-cardiac actin mRNA did not change after infarction. These findings suggest that: (1) intracellular Ca2+ handling system after myocardial infarction may be different between adjacent and remote non-infarcted myocardium: and that (2) both decreased gene expression of SR Ca2+-ATPase and Na+-Ca2+ exchanger in the adjacent non-infarcted myocardium may progress cardiac dysfunction.

Animals↗
PubMed1997

Contractile effects of porcine galanin(1-29)-NH2 on the rat isolated gastric fundus: mediation by potassium ions.

Galanin (3-300 nM) evoked reproducible concentration-dependent contractions of rat isolated gastric fundus strips, EC50 of the peptide equalled 16.7 nM (6.2-39.2) and the slope of the concentration-response curve was 34.8 (24.0-45.7). The maximal response (Emax) to carbachol (30 nM) was not affected by the absence of the potassium ions in the bathing solution. On the contrary the Emax to galanin (300 nM) was decreased by almost 95% by the use of the potassium-free buffer. Re-exposure of the muscle strips to potassium containing bathing medium reversed the inhibition by about 35%, yet the value remained significantly lower than that of the control. Apamin (1 and 2 microM), glybenclamide (10 microM), clofilium tosylate (10 microM) did not significantly influence the Emax to carbachol. Apamin or glybenclamide did not affect the contractile action of galanin, while clofilium attenuated the Emax to the peptide in a concentration-dependent manner, the EC50 of the agent being 9.44 microM (164 nM-541 microM). It was concluded that the potassium ions play a modulatory role in gastric smooth muscle contraction following galanin receptor stimulation, probably by interacting with the extracellular calcium influx.

Animals↗
PubMed1997

Role of nitric oxide in pathogenesis of serotonine-induced gastric lesions in rats.

We investigated the role of nitric oxide (NO) in the development of gastric mucosal lesions induced by serotonine (5-HT) in rats. Repeated subcutaneous administration of 5-HT (20 mg kg-1) produced damage in the stomach with severe edema in the submucosa. Gastric lesions induced by 5-HT were prevented by simultaneous administration of aminoguanidine, a selective inducible NO synthase (iNOS) inhibitor, as well as by methysergide, a 5-HT antagonist. In addition, the lesions were inhibited by pretreatment with the antioxidative drugs, such as allopurinol (a xanthine oxidase inhibitor) and hydroxyurea (a neutrophil reducing agent). Following 5-HT treatment, the Ca(2+)-independent NOS activity in the gastric mucosa was significantly increased within 6 h and remained elevated for 2 days thereafter. The serum NOx levels increased 12 h after the administration of 5-HT, reaching a peak 24 h later. Gastric mucosal thiobarbituric acid (TBA) reactants and myeloperoxidase (MPO) activity were also significantly increased after 2 days treatment with 5-HT. Our results suggest that: (1) the repeated administration of 5-HT induced inflammatory gastric lesions in the rat stomach; (2) iNOS is upreguated during 5-HT treatment, and NO produced by iNOS contributes to development of gastric lesions in response to 5-HT, in addition to the oxyradical formation, and (3) the deleterious role of NO in this model may be accounted for by a cytotoxic action of peroxynitrite that is formed in the presence of NO and superoxide radicals.

Animals↗
PubMed1997

High incidence of angiotensin I converting enzyme genotype II in Kawasaki disease patients with coronary aneurysm.

UNLABELLED: A 287 base pair insertion/deletion polymorphism in intron 16 of the angiotensin I converting enzyme (ACE) gene was examined by polymerase chain reaction in 36 Kawasaki disease patients (16 without coronary aneurysm, 20 with coronary aneurysm). A polymorphism in the ACE gene was characterized by three genotypes: two D alleles (genotype DD), two I alleles (genotype II), and heterozygous allele (genotype DI). Genotype II was found in 65% of the patients with aneurysm and 12.5% of those without aneurysm (P < 0.01, odds ratio 13.0, 95% confidence intervals). CONCLUSION: Patients with Kawasaki disease and coronary aneurysm more often than expected had the genotype II suggesting that reactions induced by the type of ACE polymorphism predispose to coronary aneurysm formation.

Age of Onset↗
PubMed1997

Failure of the nitric oxide synthase inhibitor to stimulate duodenal bicarbonate secretion in streptozotocin-diabetic rats.

We examined the HCO(3)- stimulatory effects of L-NAME (N(G)-nitro-L-arginine methyl ester) in the proximal duodenum of streptozotocin (STZ)-induced diabetic rats and compared with those of 16,16-dimethyl prostaglandin E2 (dmPGE2) and vagal electrical stimulation. Male SD rats were given STZ (70 mg/kg) i.p., and the experiments were done using 1 approximately 6 week STZ-diabetic rats with blood glucose levels of >300 mg/dl. Under urethane anesthesia the HCO(3)- secretion was measured in the proximal duodenal loop using a pH-stat method and by adding 10 mM HCl. Hyperglycemic conditions appeared 1 week after STZ treatment and remained during 6 week-test period. The duodenal HCO(3)- secretory response to L-NAME was significantly decreased in STZ-diabetic rats; the degree of reduction was dependent on the duration of diabetes, and the stimulatory effect disappeared completely in rats after 5 approximately 6 weeks of diabetes. Intravenous administration of L-NAME markedly increased arterial blood pressure with significant decrease in heart rate in normal rats, whereas in STZ-diabetic rats this agent caused only pressor response without any effect on heart rate. STZ-diabetic rats also secreted significantly less amount of HCO(3)- from the duodenum in response to dmPGE2 and vagal electrical stimulation after 5 approximately 6 weeks of diabetes. These all changes observed in STZ-diabetic rats were significantly reversed by daily injection of insulin. These results suggest that 1) L-NAME failed to stimulate duodenal HCO(3)- secretion in STZ-diabetic rats, and 2) impairment of the duodenal HCO(3)- secretory ability in STZ-diabetic conditions is due to both vagal-dependent neuronal dysfunction and decreased sensitivity of the secreting cell.

16,16-Dimethylprostaglandin E2↗