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Biomedical subjects

K Takeda

Publications and source records attributed to K Takeda.

At least 415 records · Page 23Linked to original sources

No association between atopy/asthma and the ILe50Val polymorphism of IL-4 receptor.

Susceptibility to atopic diseases is known to involve genetic factors. The interleukin-4 (IL-4) receptor- alpha gene (IL4R) reportedly is involved in the development of atopy. A recent study has shown the Ile50 allele of a polymorphism (Ile50Val) of IL4R to be associated with atopy. The objective of this study was to replicate this association and confirm the possible role of the Ile50Val polymorphism of IL4R in the etiology of atopic asthma in a Japanese population. We conducted a transmission disequilibrium test in 86 families identified through asthmatic children. A case-control study was also carried out using both atopic and control subjects. The IL4R Ile50Val polymorphism was genotyped by a PCR-restriction fragment length polymorphism method using an intronic upstream primer. The IL4R Ile50 allele was not preferentially transmitted to atopy- or to asthma-affected children. Neither the Ile50 allele nor the Ile50/Ile50 genotype was more prevalent in the atopic subjects than in the control subjects. Our findings indicate that the Ile50Val polymorphism of IL4R does not play a substantial role in genetic predisposition for the etiology of atopy or asthma in this Japanese population.

Adolescent↗

Development of eosinophilic airway inflammation and airway hyperresponsiveness requires interleukin-5 but not immunoglobulin E or B lymphocytes.

We previously defined a role for B cells and allergen-specific immunoglobulins in the development of allergic sensitization, airway inflammation, and airway hyperresponsiveness (AHR), using a 10-d protocol in which allergen exposure occurred exclusively via the airways, without adjuvant. In the present protocol, normal and B-cell-deficient (microMt(-/-)) mice were sensitized intraperitoneally to ovalbumin (OVA) and challenged with OVA via the airways in order to examine the requirements for AHR with this protocol. T-cell activation (antigen-specific proliferative responses and Th2-type cytokine production) and eosinophil infiltration in the peribronchial regions of the airways, with signs of eosinophil activation and degranulation, occurred in both experimental groups. In contrast to the 10-d protocol, increased in vivo airway responsiveness to methacholine and in vitro tracheal smooth-muscle responses to electrical field stimulation were observed in both normal and B-cell-deficient mice, and these responses were inhibited by anti-interleukin (IL)-5 administration before airway challenge. These data show that IL-5, but not B cells or allergen-specific IgE, are required for eosinophil airway infiltration and the development of AHR following allergen/alum sensitization and repeated airway challenge with allergen. These results emphasize that the use of different sensitization and challenge protocols can influence the requirements for development of AHR.

Allergens↗

The late, but not early, asthmatic response is dependent on IL-5 and correlates with eosinophil infiltration.

Early-phase reactions (EPRs) and late-phase reactions (LPRs) are characteristic features of bronchial asthma, although the pathogenetic mechanisms responsible for each of the responses are not fully defined. A murine model of EPRs and LPRs was developed to investigate the role of IL-5 and eosinophils in development of both responses. After initial intraperitoneal sensitization and airway challenge to ovalbumin (OVA), mice were provoked by additional exposure to OVA. An EPR, characterized by a transient increase in airway responsiveness, was observed 5-30 minutes after antigen provocation. This response was followed by an LPR that reached its maximum at 6 hours after challenge and was characterized by increased airway responsiveness and significant lung eosinophilia. The EPR was blocked by cromoglycate and albuterol, whereas the LPR was abolished by cromoglycate and hydrocortisone. Before provocation with allergen, administration of anti-IL-5 antibody prevented the influx of eosinophils into the lung tissue and abolished the LPR but not EPR. These results suggest that IL-5 and eosinophils are essential for development of the LPR, but not EPR, in this model.

Administration, Inhalation↗

Correlation between serum levels of cardiac troponin-T and the severity of the chronic cardiomyopathy induced by doxorubicin.

PURPOSE: To investigate, over a wide range of cumulative doxorubicin doses, the feasibility of using serum concentrations of cardiac troponin-T (cTnT) as a biomarker for doxorubicin-induced myocardial damage. MATERIALS AND METHODS: Groups of spontaneously hypertensive rats (SHR) were given 1 mg/kg doxorubicin weekly for 2 to 12 weeks. Cardiomyopathy scores were assessed according to the method of Billingham and serum levels of cTnT were quantified by a noncompetitive immunoassay. Myocardial localization of cTnT was studied by immunohistochemical staining and confocal microscopy. RESULTS: Increases in serum levels of cTnT (0.03 to 0.05 ng/mL) and myocardial lesions (cardiomyopathy scores of 1 or 1.5) were found in one out of five and two out of five SHR given 2 and 4 mg/kg doxorubicin, respectively. All animals given 6 mg/kg or more of doxorubicin had increases in serum cTnT and myocardial lesions. The average cTnT levels and the cardiomyopathy scores correlated with the cumulative dose of doxorubicin (0.13 v 0.4 ng/mL cTnT and scores of 1.4 v 3.0 in SHR given 6 and 12 mg/kg doxorubicin, respectively). Decreased staining for cTnT was observed in cardiac tissue from SHR receiving cumulative doses that caused only minimal histologic alterations (scores of 1 to 1.5). Staining for cTnT decreased simultaneously with increases in the severity of the cardiomyopathy scores. CONCLUSION: cTnT is released from doxorubicin-damaged myocytes. Measurements of serum levels of this protein seem to provide a sensitive means for assessing the early cardiotoxicity of doxorubicin.

Animals↗

[Decreased plasma levels of omeprazole after coadministration with magnesium-aluminium hydroxide dry suspension granules].

Plasma levels of omeprazole (OPZ) in Japanese male subjects were compared after a single oral administration of 20 mg of OPZ enteric-coated tablets with and without coadministration of Maalox (MLX suspension) or Maalox dry suspension granules (MLX granules). After coadministration of MLX granules, plasma levels of OPZ markedly decreased, and area under the blood concentration-time curve (AUC) decreased to 26% of that of OPZ alone. In contrast, only a slight decrease in AUC was observed after coadministration of OPZ and MLX suspension. Both MLX suspension and MLX granules exhibited similar degrees of the inhibitory effect on the renal excretion of levofloxacin. It was suggested that a specific and unexpected drug interaction occurred between OPZ enteric-coated tablets and MLX granules via a distinct mechanism from that reported for fluoroquinolones and MLX suspension.

Administration, Oral↗

Dominant distribution of mitochondrial DNA from recipient oocytes in bovine embryos and offspring after nuclear transfer.

In the process of nuclear transfer, heteroplasmic sources of mitochondrial DNA from a donor cell and a recipient oocyte are mixed in the cytoplasm of the reconstituted embryo. The distribution of mitochondrial DNA heteroplasmy in nuclear transfer bovine embryos and resultant offspring was investigated by measuring polymorphism in the displacement loop region of mitochondrial DNA using PCR-mediated single-strand conformation polymorphism. Most offspring (20 of 21 calves) from recipient oocytes of undefined mitochondrial DNA genotypes showed different genotypes from the mitochondrial DNA of donor cells. The single calf that was an exception showed heteroplasmy, including the donor mitochondrial DNA genotype. Six cloned calves were produced from oocytes of a defined mitochondrial DNA genotype. All of these clonal members and various tissues showed only the mitochondrial DNA genotype derived from the oocyte. The mitochondrial DNA from donor cells appeared to be eliminated during early embryonic development; it gradually decreased at the early cleavage stages and was hardly detectable by the blastocyst stage. These results indicate that the genotype of mitochondrial DNA from recipient oocytes may become the dominant category of mitochondrial DNA in calves resulting from nuclear transfer.

Animals↗

Detection of telomerase activity in exfoliated cancer cells obtained from bile.

Telomerase is detected by the telomeric repeat amplification protocol (TRAP) assay in more than 85% of primary cancers. In the present study, we determined telomerase activity using exfoliated bile cells obtained from biliary tract neoplasia specimens. The aim of this study was to provide additional information regarding minimally invasive approaches to the detection of biliary tract cancer in combination with routine cytologic examination. We analyzed for telomerase activity bile juice from patients with gallbladder carcinoma, cholangiocarcinoma, cholecystitis and cholangitis. Semiquantitative determination of telomerase activity was performed using both a fluorescence-based TRAP assay on cell extracts and at the cellular level by an in situ TRAP assay. The fluorescence-based TRAP assay detected bile telomerase activity in samples from 4 of 10 patients with biliary tract cancer. In contrast, the in situ TRAP assay detected telomerase positive cells in samples from 6 of 10 patients with biliary tract cancer. However, only one of these samples showed class V cytology. A combination of semiquantitative analysis and an in situ TRAP assay to detect telomerase positive cells may improve the diagnosis of biliary tract cancers with the combination of routine cytologic examination.

Adult↗

Adjuvant immunotherapy using fibroblasts genetically engineered to secrete interleukin 12 prevents recurrence after surgical resection of established tumors in a murine adenocarcinoma model.

BACKGROUND: To explore effective therapeutic strategy against cancer of the gastrointestinal tract, tumor vaccination using fibroblasts secreting interleukin-12 (IL-12) was developed as an adjuvant therapy against murine tumor after surgical resection. METHODS: Initially, IL-12 was genetically engineered into fibroblasts (IL-12/3T3 cells), and then we evaluated in vivo and in vitro antitumor effects. In the vaccination model, irradiated C-26 tumor mass was reinoculated intradermally with IL-12/3T3 cells in mice as a tumor vaccine to examine how much it suppresses tumor recurrence. RESULTS: IL-12/3T3 cells producing 7.2 ng/10(6) cells/24 h murine IL-12 in vitro exerted dose-dependent potent tumor suppression when coinoculated with C-26 cells in vivo. Specific immunity was also acquired in 63% of mice in vivo. In the vaccination model, protective immunity was developed in 70% of mice that were inoculated with irradiated tumor mass and IL-12/3T3 cells. In addition, local recurrence was not observed in vaccinated mice, although 44% of control mice had recurrence. CONCLUSIONS: Coinoculation of genetically engineered fibroblasts secreting IL-12 with irradiated tumor mass was proved to be an effective tumor vaccine. This system of vaccination is easily applicable to clinical situations, particularly to human gastrointestinal tract cancers.

Adenocarcinoma↗

Reperfusion accelerates the distribution of type I and III collagen messenger RNA expression after acute myocardial infarction: in situ hybridization in experimental infarction in rats.

BACKGROUND: The effects of reperfusion on the time-dependent appearance and distribution of type I and III collagen messenger RNA (mRNA) expression had not hitherto been examined. OBJECTIVE: To compare the sequential changes in the extent of distribution of type I and III collagen mRNA expression in reperfused infarct hearts of rats with those in unreperfused infarct hearts. METHODS: Using an experimental rat model of infarction, we examined type I and III collagen mRNA expression with specific rat pro alpha 1 (I) and human pro alpha 1 (III) collagen riboprobes by in-situ hybridization. Reperfusion was established after a 2 h coronary ligation that produced complete necrosis of the myocytes. RESULTS: Positive signals both for alpha 1 (I) and for alpha 1 (III) collagen mRNA appeared in the infarct peripheral zone 12 h after coronary ligation both of the reperfused and of unreperfused hearts. The spread of signal into the infarct central zone occurred 1-2 days earlier for the reperfused hearts than it did for the unreperfused hearts. The difference between the distributions of signals for the reperfused and unreperfused hearts became obscure on day 14. No notable difference between the extents of signal distribution for alpha 1 (I) and alpha 1 (III) collagen mRNA was obtained. We observed intense signals from spindle-shaped mesenchymal cells (myofibroblasts and fibroblasts) located between surviving myocytes in the marginal zone of the infarct. No myocyte exhibited signals both for alpha 1 (I) and for alpha 1 (III) collagen mRNA. CONCLUSION: In the present study, using in-situ hybridization, we demonstrated that reperfusion accelerates the distribution of expression both of alpha 1 (I) and of alpha 1 (III) collagen mRNA in the infarct zone after acute myocardial infarction in rats.

Animals↗

[Therapeutic strategy for the recurrence of pancreatic cancer following pancreatectomy].

It is well-known that the patients with pancreatic cancer are vulnerable for recurrence such as local relapse and liver metastasis after surgical resection. We revealed that a patient with local relapse without liver metastasis showed better prognosis as compared with a patient having liver metastasis. We usually adapt further therapeutic intervention for local recurrence using external radiation therapy accompanied with 5FU infusion as a radiosensitizer, if the patient is not revealed with liver metastasis. On the other hand, there is no effective intervention for liver metastasis accompanying pancreatic cancer, as small lesions of multiple liver metastases progress rapidly. We insert the tip of catheter in proper hepatic artery in order to infuse MMC once a week at outpatient clinic. However, we were not yet able to evaluate the effect of arterial infusion therapy.

Infusions, Intra-Arterial↗

[A case of nephrotic syndrome with diabetes mellitus and primary aldosteronism].

A 65-year-old man had been followed by a family doctor for the treatment of hypertension and chronic hepatitis (type C) for about 20 years. Although he was pointed out to have impaired glucose tolerance and primary aldosteronism in 1995, he refused an adrenal tumor operation. He was admitted to our hospital on December, 1997 for further evaluation of general malaise, pitting edema of the legs, and positive urinary protein. A diagnosis of nephrotic syndrome was made on admission and a renal biopsy was performed. Histological findings indicated that he was at the early phase of diabetic nephropathy and hypertensive renal sclerosis. It is commonly believed that diabetic nephropathy develops after ten years of diabetic history and under poor control conditions. The diabetic history of this patient was only several years and the disease was under good control. In contrast to blood glucose, hypertension was not well-controlled with any antihypertensive drug, because he had a primary aldosteronism. Unfortunately, he could not take a spironolactone because of side effects. After removal of his adrenal tumor, his blood pressure was normalized gradually, and concomitantly his urinary protein was reduced and plasma protein and albumin were restored. Hypokalemia also disappeared. These findings suggest that uncontrolled hypertension may have accelerated the condition of diabetic nephropathy. The data indicates that the control of hypertension is important for inhibiting the progression of diabetic nephropathy.

Aged↗

[A comparative study of a thick and standard loop in transurethral resection of the prostate].

We compared the safety and efficacy of transurethral resection of the prostate (TURP) with a thick loop and with a standard loop. We compared 36 consecutive men (median age, 70 years) with symptomatic benign prostatic hyperlasia (BPH) treated by TURP with a thick loop to a cohort of 36 men (median age, 72 years) treated by TURP with a standard loop. The safety parameters of evaluation included the operative time, blood loss, chronological changes in serum sodium, and complications. The efficacy parameters of evaluation included International Prostate Symptom Score, quality of life assessment, peak urinary flow rate, and post-void residual urine volume. The operative time (median, 49.5 versus 43.5 minutes), blood loss (median, 179 versus 127 ml), and change in serum sodium (median, -4.0 versus -6.0 mEq/L) were not significantly greater in the thick loop group than in the standard loop group, respectively. There were no major complications in either group. Clinically significant improvement was observed in all efficacy parameters in both groups, with no difference between the two groups. These results suggest that TURP with a thick loop is not necessarily superior to TURP with a standard loop in terms of decreasing the blood loss and decreasing the operative time.

Aged↗

Feasibility of simultaneous stress 99mTc-sestamibi/rest 201Tl dual-isotope myocardial perfusion SPECT in the detection of coronary artery disease.

UNLABELLED: This study assesses feasibility and diagnostic accuracy of simultaneous stress 99mTc-sestamibi/rest 201 TI dual-isotope myocardial perfusion SPECT with Moore's correction method, in which contamination originating from lead x-rays produced in a collimator was subtracted in the 201TI windows. METHODS: Eighty-one patients with suspected coronary artery disease received exercise 99mTc-sestamibi injection, followed by rest 201TI injection 50 min later, and dual-isotope SPECT was performed (group 1). These results were compared with coronary angiographic findings. Furthermore, to estimate the accuracy of Moore's correction method, 201TI crosstalk into the 99mTc acquisition window (group 2A, n = 20) and 99mTc crosstalk into the 201TI acquisition windows (group 2B, n = 20) were studied. For group 2A, stress 99mTc-sestamibi SPECT (single 99mTc-sestamibi SPECT) was performed, followed by 201TI injection at rest and dual-isotope SPECT acquisition 50 min later. For group 2B, rest 201TI SPECT (single 201TI SPECT) was performed, followed by 99mTc-sestamibi injection at rest and dual-isotope SPECT acquisition 30 min later. RESULTS: Sensitivity and specificity in group 1 were 83% and 99%, respectively, when > or =75% coronary artery narrowing was considered significant. In groups 2A and 2B, SPECT images were divided into 24 segments, and relative regional uptake in each segment was obtained. In group 2A, relative regional uptake of single 99mTc-sestamibi SPECT correlated well with that of dual-isotope SPECT (r = 0.942). In group 2B, relative regional uptake of single 201TI SPECT correlated well with that of dual-isotope SPECT (r = 0.935). Furthermore, in low 201TI uptake segments with relative regional uptake in both single- and dual-isotope SPECT of < or =70%, the degree of concordance between single- and dual-rest 201TI was considered to be high with Bland-Altman analysis and the kappa statistic. Comparison of perfusion defect type demonstrated that, of 22 stress defects within infarct zones, 95% were irreversible and 5% were reversible. In contrast, of 28 stress defects within stenosed vessel zones in noninfarct zones, 89% were reversible and 11% were irreversible (P < 0.0001 versus infarct zones). CONCLUSION: Simultaneous dual-isotope imaging with Moore's correction method is feasible, with acceptable accuracy for detection of coronary artery disease and a small amount of crosstalk into each window.

Aged↗

[Early and mid-term results of endovascular stent grafting for aortic aneurysms].

Early and mid-term clinical results of 28 cases of endovascular stent grafting for descending thoracic aortic aneurysms and 11 cases of abdominal aortic aneurysms are reported. Early clinical results: Among 28 patients (7 true thoracic aortic aneurysms, 3 pseudothoracic aortic aneurysms and 8 acute, 4 subacute, and 6 chronic aortic dissections), two patients (7.1%) with ruptured acute aortic dissection or ruptured infected pseudoaneurysm died in the perioperative period. Two of the remaining 26 patients experienced minor complications. Aneurysmal sacs or false lumens at the descending thoracic aorta were completely thrombosed in the 26 patients. One patient (9.1%) with a ruptured abdominal aneurysm died, and one of the remaining 10 patients had renal and peripheral emboli and peripheral vascular trauma. Inadvertent covering of the renal arteries occurred in another patient. Unless one patient had persistent endoleak, aneurysmal sacs in the 10 surviving patients were thrombosed. Mid-term clinical results: One aortic dissection at a different section of the descending aorta occurred 6 months after stent grafting for aortic dissection, and one patient died of pneumonia 3 months after stent grafting for an abdominal aortic aneurysm. CT scanning 6 months after stent grafting revealed a decrease in maximal aneurysmal size in 3 of 9 patients with true or pseudothoracic aneurysms and in 2 of 5 patients with abdominal aortic aneurysms. Five of 9 patients with stent grafting for acute or subacute dissection showed elimination of the false lumen in the descending thoracic aorta in a CT scan 6 months after grafting. One patient with a true thoracic aneurysm and one patient with an abdominal aortic aneurysm showed an increase in aneurysmal size in a CT scan 2 years and one year after treatment, respectively.

Aged↗

[The progress in diagnostic imaging for staging of bladder and prostate cancer: endorectal magnetic resonance imaging and magnetization transfer contrast].

We retrospectively studied the staging accuracy of endorectal magnetic resonance imaging (MRI) in comparison with transrectal ultrasound examination (TRUS) for 71 localized bladder cancers and 19 localized prostate cancers (PC) radically resected. The accuracy of clinical staging for bladder cancer in endorectal MRI and TRUS was 85.9% and 69.2%, respectively. The presence or absence of the continuity of submucosal enhancement on T2-weighted MRI images could be useful for the staging of bladder cancer. The accuracy of the seminal vesicular invasion for prostate cancer in endorectal MRI and TRUS was 95% and 63%, respectively. To determine whether magnetization transfer contrast (MTC) provides additional information in the diagnosis of prostate cancer, the magnetization transfer ratios (MTRs) were calculated in 22 patients with PC, 5 with benign prostatic hyperplasia (BPH) and 4 controls. The mean MTR in the peripheral zone of the normal prostate (8.0% +/- 3.4 [standard deviation]) showed a statistically significant decrease relative to that in the inner zone of the normal prostate (27.4% +/- 3.4, p < 0.01), BPH (25.5% +/- 3.7, p < 0.01), pre-treatment PC (30.6% +/- 5.9, p < 0.01), and PC after hormonal therapy (20.3% +/- 6.3, p < 0.01). The mean MTR in pre-treatment PC was significantly higher than that in BPH, or in PC after hormonal therapy (p < 0.01). MTC was considered to be useful for conspicuity of prostate cancer lesion.

Gadolinium DTPA↗

[The future guaranteeing the advanced accuracy].

To guarantee the supply of accurate clinical information, the laboratory system uses external quality control, internal quality control, and data checking method. The correlation among these laboratory items and the continuity of the inter-subject variation are applied to self-acting assessment of data. In this text, we introduce other insights, not yet generalized to date, to guarantee the accuracy. First, we emphasize the importance of accurate data communication and redundancy of composition in the information equipment to improve the reliability of information transaction. Secondly, we applied the data checking system which synchronizes with pathophysiological changes in the patients to the diagnosis support system using the hypothesis deduction method. Thirdly, we present the mobility presumption method in the seat of protein electrophoresis crimp as a suitable example to obtain more accurate information processing of the original data.

Clinical Laboratory Information Systems↗

[Phase 1 clinical study of 123I-FP-CIT, a new radioligand for evaluating dopamine transporter with SPECT (I): Biodistribution and absorbed dose].

A Phase 1 clinical study of 123I-FP-CIT, N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane (123I), developed for evaluation of dopamine transporter (DA-T) by single photon emission computed tomography (SPECT), was performed in 12 healthy male volunteers. No adverse reactions to 123I-FP-CIT (167 MBq) injection were observed. In sequential whole-body images after intravenous injection, the radioactivity was distributed mainly in the liver, abdomen, lungs and brain, and it decreased gradually with time. The radioactivity was excreted mainly in the urine and no prolonged retention of radioactivity was observed in any organs at 2 days post-injection. The radiation absorbed dose of 123I-FP-CIT, calculated on the basis of the pharmacokinetics, was equal to or less than those of other brain diagnostic imaging agents. These results suggest that i.v. injection of 123I-FP-CIT causes no significant problems in terms of its safety, biodistribution or absorbed dose.

Adult↗