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Biomedical subjects

K Takeda

Publications and source records attributed to K Takeda.

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

Normal bladder wall morphology in Gd-DTPA-enhanced clinical MR imaging using an endorectal surface coil and histological assessment of submucosal linear enhancement using [14C]Gd-DOTA autoradiography in an animal model.

OBJECTIVE: The purpose of this study was to investigate normal bladder wall morphology in gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced magnetic resonance (MR) imaging using an endorectal surface coil and to perform histological assessment of submucosal linear enhancement with experimental [14C]-gadolinium-tetraazacyclododecane-tetraacetic acid (Gd-DOTA) autoradiography. METHODS AND MATERIAL: MR imaging of the bladder was performed using an endorectal coil in 13 consecutive patients with bladder carcinoma and T1-, T2-, and Gd-DTPA-enhanced spin-echo images of the bladder wall were compared. After injection of [14C]Gd-DOTA into a hamster, autoradiograms of the bladder wall were obtained and compared with serial histological sections. RESULTS: The normal bladder wall appeared as a homogeneous layer of intermediate intensity on T1-weighted images. After administration of Gd-DTPA, the bladder wall was visualized as three layers: an inner thin layer of low intensity, a middle layer of marked enhancement, and a thick outer layer of intermediate intensity. The autoradiograms demonstrated dense accumulation of [14C]Gd-DOTA in the submucosal layer. Thus, the inner, middle, and outer layers corresponded to the mucosa, submucosa, and muscularis propria, respectively. The thickness of the bladder wall demonstrated on T2-weighted images was almost equal to that of the outer layer on enhanced T1-weighted images. Thus, T2-weighted images revealed only the muscle layer as an intermediate-intensity band. In the preliminary clinical study, MR imaging invariably showed accurate stages of the bladder carcinoma in 13 patients. CONCLUSION: In MR imaging of the normal bladder wall, the submucosa was strikingly enhanced after Gd-DTPA administration, separating the bladder wall into three layers. This may have a potential role in the staging of bladder tumors.

Animals↗
PubMed1998

Enzyme-linked immunosorbent assay for TA-2005-glucuronide in human plasma.

A sensitive enzyme-linked immunosorbent assay (ELISA) for TA-2005-glucuronide, a main metabolite of new adrenergic beta-receptor agonist TA-2005, has been investigated without prior deconjugation. Coupling of the hapten with bovine serum albumin (BSA) or beta-D-galactosidase was carried out by the N-hydroxysuccinimide ester method. An anti-TA-2005-glucuronide antiserum was obtained from guinea pig immunized with the hapten-BSA conjugate. The ELISA was based upon a competitive assay in which the separation of bound from free fraction was performed by the double antibody technique using rabbit anti guinea pig immunoglobulin antibody adsorbed to microtiter plates. A satisfactory standard curve for the ELISA of TA-2005-glucuronide was observed in the range of 30 pg-3 ng ml-1 using 25 microliters of human plasma. Inter-day and intra-assay variations were 7.0-17.5% and 1.0-11.7% respectively. The recoveries of TA-2005-glucuronide spiked to plasma samples were 95.5-120% (inter-assay) and 96.0-123.3% (intra-assay). The cross-reactivities of the prepared antiserum with the related compound of TA-2005-glucuronide were quite low though there was a considerable cross-reaction with TA-2005. However, TA-2005-glucuronide could be easily separated from TA-2005 by a simple pretreatment of the plasma sample with a C18 cartridge column. This method was applied to the determination of TA-2005-glucuronide in human plasma samples for the evaluation of the pharmacokinetics of TA-2005. From the results, it was demonstrated that the ELISA developed was useful for the determination of TA-2005-glucuronide in human plasma and that the method was applicable to pharmacokinetic studies in humans.

Administration, Oral↗
PubMed1998

Unique association of pheochromocytoma with contralateral nonfunctioning adrenal cortical adenoma.

A 57-year-old woman complaining of hypertensive attacks associated with headache and palpitation was admitted to our hospital for examination of bilateral adrenal tumors in 1985. After right pheochromocytoma was diagnosed, right adrenalectomy was performed. The left adrenal tumor was small; thus, the left adrenal tumor was preserved to avoid adrenal insufficiency, although left adrenal pheochromocytoma could not be denied. In 1995, she was referred to our clinic again because of recurrent headache and palpitation, and enlargement of the left adrenal tumor. Although pheochromocytoma was suspected again, the enlarged left adrenal turned out to be a nonfunctioning cortical adenoma. This case was interesting, not only because of difficulty in identifying the left adrenal tumor, but also because of the rare coexistence of a pheochromocytoma and a nonfunctioning adrenal cortical tumor.

Adrenal Cortex Neoplasms↗
PubMed1998

A case of therapy-related acute myeloblastic leukemia with t(16;21)(q24;q22) after chemotherapy with DNA-topoisomerase II inhibitors, etoposide and mitoxantrone, and the alkylating agent, cyclophosphamide.

A 59-year-old female suffering from malignant lymphoma developed therapy-related acute myeloblastic leukemia (t-AML) after chemotherapy consisting of treatment with DNA-topoisomerase II inhibitors, etoposide and mitoxantrone, and an alkylating agent, cyclophosphamide. The cumulative dose of etoposide administration was 5500 mg; 1500 mg given intravenously and 4000 mg orally. One year later, she suddenly developed AML of FAB M2. Cytogenetic analysis of bone marrow cells revealed deletion of 7q and a rare translocation, t(16;21)(q24;q22). Southern blot analysis of bone marrow cells did not detect rearrangement of the AML1 gene, however, fluorescence in situ hybridization (FISH) analysis of bone marrow cells at interphase and metaphase revealed a translocational splitting between chromosome 21 involving AML1 gene and chromosome 16. These results suggest that the breakpoint is not located in the breakpoint cluster region for t(8;21). The patient was treated with chemotherapy and entered complete remission.

Alkylating Agents↗
PubMed1998

Defective NK cell activity and Th1 response in IL-18-deficient mice.

IL-18 is a cytokine that is secreted from activated macrophages and induces IFNgamma production. To investigate the in vivo role of IL-18, we generated IL-18-deficient mice. In Propionibacterium acnes (P. acnes)-primed IL-18-deficient mice, LPS-induced IFNgamma production was markedly reduced, despite normal IL-12 induction. Natural killer cell activity was significantly impaired. Th1 cell response after injection of P. acnes or Mycobacterium bovis (bacillus Calmette-Guerin [BCG]) was significantly reduced. Similar results were observed in IL-12-deficient mice. Interestingly, Th1 response was induced after BCG infection in IL-12-deficient mice. We therefore generated mice lacking both IL-18 and IL-12. In these mice, NK activity and Th1 response were further impaired. This demonstrates the important role of both IL-18 and IL-12 in NK activity, as well as in in vivo Th1 response.

Animals↗
PubMed1998

Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function.

MyD88, originally isolated as a myeloid differentiation primary response gene, is shown to act as an adaptor in interleukin-1 (IL-1) signaling by interacting with both the IL-1 receptor complex and IL-1 receptor-associated kinase (IRAK). Mice generated by gene targeting to lack MyD88 have defects in T cell proliferation as well as induction of acute phase proteins and cytokines in response to IL-1. Increases in interferon-gamma production and natural killer cell activity in response to IL-18 are abrogated. In vivo Th1 response is also impaired. Furthermore, IL-18-induced activation of NF-kappaB and c-Jun N-terminal kinase (JNK) is blocked in MyD88-/- Th1-developing cells. Taken together, these results demonstrate that MyD88 is a critical component in the signaling cascade that is mediated by IL-1 receptor as well as IL-18 receptor.

Adaptor Proteins, Signal Transducing↗
PubMed1998

ASK1 is essential for JNK/SAPK activation by TRAF2.

Tumor necrosis factor (TNF)-induced activation of the c-jun N-terminal kinase (JNK, also known as SAPK; stress-activated protein kinase) requires TNF receptor-associated factor 2 (TRAF2). The apoptosis signal-regulating kinase 1 (ASK1) is activated by TNF and stimulates JNK activation. Here we show that ASK1 interacts with members of the TRAF family and is activated by TRAF2, TRAF5, and TRAF6 overexpression. A truncated derivative of TRAF2, which inhibits JNK activation by TNF, blocks TNF-induced ASK1 activation. A catalytically inactive mutant of ASK1 is a dominant-negative inhibitor of TNF- and TRAF2-induced JNK activation. In untransfected mammalian cells, ASK1 rapidly associates with TRAF2 in a TNF-dependent manner. Thus, ASK1 is a mediator of TRAF2-induced JNK activation.

Animals↗
PubMed1998

Epistatic relationship between Waardenburg syndrome genes MITF and PAX3.

Waardenburg syndrome (WS) is a hereditary disorder that causes hypopigmentation and hearing impairment. Depending on additional symptoms, WS is classified into four types: WS1, WS2, WS3 and WS4. Mutations in MITF (microphthalmia-associated transcription factor) and PAX3, encoding transcription factors, are responsible for WS2 and WS1/WS3, respectively. We have previously shown that MITF transactivates the gene for tyrosinase, a key enzyme for melanogenesis, and is critically involved in melanocyte differentiation. Absence of melanocytes affects pigmentation in the skin, hair and eyes, and hearing function in the cochlea. Therefore, hypopigmentation and hearing loss in WS2 are likely to be the results of an anomaly of melanocyte differentiation caused by MITF mutations. However, the molecular mechanism by which PAX3 mutations cause the auditory-pigmentary symptoms in WS1/WS3 remains to be explained. Here we show that PAX3, a transcription factor with a paired domain and a homeodomain, transactivates the MITF promoter. We further show that PAX3 proteins associated with WS1 in either the paired domain or the homeodomain fail to recognize and transactivate the MITF promoter. These results provide evidence that PAX3 directly regulates MITF and suggest that the failure of this regulation due to PAX3 mutations causes the auditory-pigmentary symptoms in at least some individuals with WS1.

Binding Sites↗
PubMed1998

Characterization, chromosomal localization, and genetic variation of the alpha subunit of porcine eighth component of complement.

The complete amino acid sequence of the porcine alpha subunit of the eighth component of complement (C8A) was determined by characterizing the full length cDNA clone isolated from a porcine liver cDNA library. Porcine C8A was found to be similar to human and rabbit C8A in length, leader sequence, conserved cysteine residues, cysteine-rich modules, and overall sequence. Differences in the amino acid sequence among the three species were detected in the proposed candidate site for CD59 recognition (amino acids 352-389). The porcine C8A gene was physically mapped to chromosome 6q33-35 by in situ hybridization using the porcine bacterial artificial chromosome (BAC) clone as a hybridization probe. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of C8A was performed using the restriction enzyme Hha I. Distribution of the alleles was determined in pigs (n = 173) of several different breeds. Estimates of allele frequency of the 201 bp fragment were 0.22,.0.43,.0.04,.0.50,.0.58,.0.50,.0.98, and 0.91 in Landrace, Large White, Duroc, Berkshire, Jinhua, Crown Miniature Pig, wild boar, and Meishan, respectively.

Alleles↗
PubMed1998

Association of asthma and the interleukin-4 promoter gene in Japanese.

BACKGROUND: Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components. Several investigator have linked the interleukin-4 (IL-4) gene and nearby markers located on chromosome 5 to atopy and asthma. Recent study has demonstrated that the T allele of a polymorphism in the IL-4 gene promoter region (C-590T) is associated with elevated levels of total serum IgE. OBJECTIVE: The objective of this study was to evaluate the possible role of this IL-4 polymorphism (C-590T) in modulating the allergic response and asthma in Japanese children. METHODS AND RESULTS: The study was conducted in two different populations: families ascertained through asthmatic children (asthmatic group, 306 members) in whom linkage of asthma and atopy to chromosome 5q31-33 is suggested and a random general population (control group, 215 members). The IL-4 C-590T polymorphism was genotyped by PCR-restriction fragment length polymorphism analysis. Frequency of the T allele was 0.73 in the asthmatic group and 0.70 in the control group. No significant difference in the levels of total serum IgE and specific IgE to house dust mite was observed between subjects with homozygote for the C allele, a heterozygote and a homozygote for the T allele by intrafamilial and interfamilial comparisons. Using the transmission disequilibrium test, however, we found a significantly frequent transmission of the T allele to asthmatic children (chi2=5.72, P=0.023). CONCLUSION: Our data suggest that the IL-4 promoter C-590T polymorphism may be associated with the development of asthma in Japanese children, but not through modulating total serum IgE levels.

Adolescent↗
PubMed1998

Targeted disruption of ATF4 discloses its essential role in the formation of eye lens fibres.

BACKGROUND: Activating transcription factor-4 (ATF4)--also termed CREB2, C/ATF, and TAXREB67--is a basic-leucine zipper (bZip) transcription factor that belongs to the ATF/CREB family. In addition to its own family members, ATF4 can also form heterodimers with other related but distinct bZIP proteins such as the C/EBP, AP-1 and Maf families, which may give rise to a variety of combinatorial diversity in gene regulation. In order to assess the in vivo essential role of ATF4, we have generated mice lacking ATF4 by gene targeting. RESULTS: ATF4-deficient mice exhibited severe microphthalmia. Although ATF4-deficient eyes revealed a normal gross lens structure up to embryonic day 14.5, later on the ATF4-deficient lens, degenerated due to apoptosis without the formation of lens secondary fibre cells. Retinal development was normal in the mutant mice. The lens-specific expression of ATF4 in the mutant mice led not only to the recovery of lens secondary fibres but also to the induction of hyperplasia of these fibres. CONCLUSION: These results demonstrated that ATF4 is essential for the later stages of lens fibre cell differentiation.

Activating Transcription Factor 4↗
PubMed1998

An allogeneic microenvironment influences the phenotype of intermediate T-cell receptor cells expanding in MRL-lpr/lpr mice.

MRL-lpr/lpr (lpr) mice fall victim to autoimmune disease owing to a lymphoproliferative disorder mainly of double-negative (DN) CD4- CD8- alpha beta T cells expressing a low density of interleukin-2 receptor beta-chain (IL-2R beta). It was previously revealed that the lpr gene is a defective Fas gene, into which an early transposon (ETn) of retrovirus is transfected. As a result of the failure of apoptosis, intermediate T-cell receptor (TCR) cells (i.e. TCRint cells) with DN phenotype abnormally accumulate in the periphery of lpr mice. We investigated herein how these TCRint cells are selected in terms of CD4, CD8 and TCR in lpr mice. When a whole fraction of mononuclear cells (MNC) in various immune organs of lpr mice was injected into scid mice (allogeneic circumstance), CD8+ TCRint cells mainly expanded. They had a high density of IL-2R beta. This was true when bone marrow cells of lpr mice were injected into scid mice. On the other hand, when MNC of the spleen and bone marrow in lpr mice were injected into irradiated (9 Gy) lpr mice (syngeneic circumstance), the major expanding cells were DN TCRint cells expressing a low density of IL-2R beta. A cell-sorting experiment for purified fractions demonstrated that only CD8- cells reconstituted TCRint cells in scid mice. Namely, DN CD4- CD8- cells as well as CD4+ cells which once acquired the mature phenotype, no longer switched their phenotype. These results suggest that the phenotype of TCRint cells is influenced by the surrounding microenvironment.

Animals↗
PubMed1998

Pre- and post-synaptic muscarinic receptors in thin slices of rat adrenal gland.

The effects of activation of muscarinic receptors on chromaffin cells and splanchnic nerve terminals were studied in a rat adrenal slice preparation. In chromaffin cells, muscarine induced a transient hyperpolarization followed by a depolarization associated with cell spiking. The hyperpolarization was blocked by charybdotoxin (1 microM) and tetraethylammonium chloride (TEA, 1 mM), but was not affected by 200 microM Cd2+ or removal of external Ca2+, consistent with activation of BK channels. This would follow internal Ca2+ mobilization, as shown by Ca2+ imaging with fura-2 on isolated chromaffin cells in culture. Under voltage-clamp, outward BK currents were insensitive to MT3 toxin, a specific muscarinic m4 receptor antagonist. In contrast, muscarine-induced depolarization was due to a m4 receptor-mediated inward current blocked by MT3 toxin. This current was permeable to cations and was associated with Ca2+ entry and subsequently, Ca2+-induced Ca2+ release. Finally, both muscarine (25 microM) and oxotremorine (10 microM) decreased the amplitude and frequency of KCI-evoked excitatory postsynaptic currents, without affecting quantal size, consistent with a presynaptic inhibitory effect. Taken together, our data suggest that activation of m4 and probably m3 muscarinic receptors results in a strong, long-lasting excitation of chromaffin cells, as well as an uncoupling of synaptic inputs onto these cells.

Acetylcholine↗
PubMed1998

Disadvantage of long-term CAPD for preserving cardiac performance: an echocardiographic study.

The indices of cardiac performances were compared between 31 continuous ambulatory peritoneal dialysis (CAPD) and 20 long-term hemodialysis (HD) patients. They were subdivided into three groups according to dialysis duration: L-CAPD (n = 16, mean age and CAPD duration were, respectively, 53 +/- 8 [SD] years and 77 +/- 13 months); S-CAPD (n = 15; 52 +/- 12 years, 28 +/- 12 months); HD (n = 20; 51 +/- 10 years, 162 +/- 52 months). The diabetic HD patients (DM-HD; n = 13; 60 +/- 13 years of age, 22 +/- 11 months) were chosen separately. Thirteen normotensive subjects with normal kidney function (mean age, 57 +/- 9 years) were selected as an age-matched control group. There were no significant differences between groups in age, gender, incidence of original kidney disease, or serum biochemical data. The blood pressure and the cardiothoracic ratio in L-CAPD were highest among groups. The indices of left ventricular (LV) hypertrophy as well as LV performance by means of echocardiography or pulsed Doppler were compared. Among nondiabetic dialysis patients, the calculated LV mass index (LVMI) of 166.4 +/- 84.3 g/m2 and the ratio of the peak atrial filling velocity to the peak diastolic flow velocity of 1.25 +/- 0.4 in L-CAPD were greatest, and the left ventricular fractional shortening (%FS) of 34.2 +/- 10.8% in L-CAPD was smallest. LVMI or %FS of L-CAPD was the same as DM-HD of 161.0 +/- 40.7 g/m2 or 31.6 +/- 8.2%. Possibly, poor control of hypervolemia, which is caused by peritoneal problems induced by either peritonitis or chronic exposure to high-glucose dialysate, causes a substantial cardiac preload leading to incipient cardiac failure in L-CAPD. According to the similar results of L-CAPD and DM-HD, it may be that hypertension, hyperlipidemia, or long-term constant glucose loading of CAPD fluids in addition to impaired glucose tolerance by chronic renal failure is more or less related to the progression of LV hypertrophy and latent cardiac dysfunction in long-term CAPD patients. In this context, CAPD of more than 5 years' duration is disadvantageous for preserving cardiac function as compared with HD.

Adult↗
PubMed1998

Defective IL-2-mediated IL-2 receptor alpha chain expression in Stat3-deficient T lymphocytes.

Stat3, a member of signal transducers and activators of transcription (STAT), is activated by a variety of cytokines. Recently, mice lacking Stat3 specifically in T cells have been generated and shown to be defective in IL-6-induced proliferation due to the impairment in IL-6-mediated prevention of apoptosis. In the present study, we show that Stat3-deficient T cells are partially defective in IL-2-induced proliferation. Stat3-deficient T cells show impaired IL-2-mediated IL-2 receptor (IL-2R) alpha chain expression. When Stat3-deficient T cells are stimulated with high-dose IL-2, these T cells express IL-2Ralpha and proliferate to similar extents as wild-type T cells. These demonstrate that Stat3 activation is required for efficient T cell proliferation by IL-2 through IL-2Ralpha induction. Taken together, these findings demonstrate that Stat3 activation in T cells is responsible for IL-2- and IL-6-induced proliferation through distinct mechanisms.

Animals↗
PubMed1998

Successful use of single-lumen, urokinase immobilized femoral catheters as a temporary access for haemodialysis.

METHODS: Placement of a femoral vein catheter as a temporary vascular access for haemodialysis was conducted and the indications, catheter patency rate, and incidence of catheter-related infections were examined. An urokinase immobilized femoral vein catheter (UIFC) is a soft polyurethane single-lumen catheter 2.7 mm in diameter and 22 cm in length which needs no heparin infusion (Japan Shawood Co., Ltd., Tokyo; Unitica Co., Ltd., Hyogo, Japan). A soft silicon rubber was attached to the tip of the catheter in order to avoid excessive bleeding during insertion. Aseptic adhesive wound dressing was employed at the exit-site which was cleansed with popidone-iodine and renewed at each dialysis session. RESULTS: Eighty-one UIFCs were used for haemodialysis in 64 patients (acute renal failure: 11; vascular access trouble: 53; initiation of chronic dialysis: 17). The average age of the patients was 58 +/- 13 years, ranging from 26 to 80 years. The mean duration of catheter indwelling was 22.4 +/- 13.1 days. An adequate blood flow of 180-200 ml/min was obtained through UIFC and returned to another peripheral vein punctured at each dialysis session. Unexplained fever occurred in four cases while the UIFC was in place (4.9%) but culture of either blood or the catheter tip was negative for bacteria. The catheter was removed immediately and fever subsided in all cases. The overall catheter survival rate was 84% at 34 days calculated using the Kaplan-Meier method. Catheter insertion was easy to perform and no serious complications such as pulmonary embolism or septicaemia occurred. CONCLUSION: Our modified type of UIFC is very useful as a temporary access for haemodialysis with a very low incidence of catheter-related infections and no need for heparinization. Excellent catheter patency was maintained with the plug system and careful dressing techniques without unnecessary bleeding during catheter care.

Adult↗