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T Furukawa

Publications and source records attributed to T Furukawa.

At least 163 records · Page 9Linked to original sources
PubMed1999

Fur mites induce dermatitis associated with IgE hyperproduction in an inbred strain of mice, NC/Kuj.

An inbred strain of mice, NC, has been introduced as an animal model for atopic dermatitis because the mice develop dermatitis associated with severe scratch preceded by elevated serum IgE level when kept in conventional conditions. Although hypersensitivity to some environmental factors is suggested to cause dermatitis, the precise factor remains unclear. As the mice maintained under conventional conditions were often infected with fur mites, we investigated whether an infection of fur mites induces skin lesions in NC. Infection with the fur mites induced NC to develop skin lesions associated with highly elevated serum IgE, whereas no obvious skin lesions were observed in BALB/c and C57BL/6, and the elevation of serum IgE level was minimal in these two strains of mice. The role of the fur mites in the manifestation of skin lesions and IgE hyperproduction was confirmed by eliminating the fur mites by treatment with ivermectin. In addition, the existence of specific IgE antibody to Myocoptes musculinus antigen in the sera of mite-infested NC was detected by the antigen-induced histamine release from bone marrow-derived cultured mast cells after sensitization with the serum. These results suggest that continuous exposure to fur mite antigen is a potential factor in the development of dermatitis in NC. We provide a new model system of antigen-induced dermatitis for investigating the role of IgE in eliciting dermatitis.

Animals↗
PubMed1999

Influence of film and monitor display luminance on observer performance and visual search.

RATIONALE AND OBJECTIVES: The purpose of this study was to measure the influence of display luminance on detection performance and visual search behavior. The results of the study should be helpful in establishing minimally acceptable display conditions for viewing radiographs on cathode-ray tube (CRT) monitors. MATERIALS AND METHODS: Two groups of six radiologists each viewed 50 pairs of mammograms. One group viewed film images on a standard mammographic view box; the other viewed images on a high-resolution CRT monitor. Two luminance levels were studied for each display type. Observers reported on the presence or absence of masses or microcalcification clusters and on their confidence in that decision. Confidence data were analyzed by using alternative free-response receiver operating characteristic (AFROC) techniques. Eye position also was recorded as observers viewed the images. RESULTS: For both the film and monitor studies, detection performance (AFROC area under the curve) was not affected significantly by display luminance, but search behavior was. Total viewing and decision dwell times were shorter with the higher-luminance displays, especially for true-negative decisions. Significantly more fixation clusters were generated during the search of lesion-free than of lesion-containing images with the lower-luminance displays. CONCLUSION: Display luminance affects visual search performance with both film and monitor displays without affecting detection performance significantly. Higher-luminance displays yield more efficient search performance. The true-negative dwell times and number of clusters are suggestive that lower-luminance levels prolong the search and recognition of normal, lesion-free areas compared with lesion-containing areas.

Contrast Sensitivity↗
PubMed1999

Retinopathy and attenuated circadian entrainment in Crx-deficient mice.

Crx, an Otx-like homeobox gene, is expressed specifically in the photoreceptors of the retina and the pinealocytes of the pineal gland. Crx has been proposed to have a role in the regulation of photoreceptor-specific genes in the eye and of pineal-specific genes in the pineal gland. Mutations in human CRX are associated with the retinal diseases, cone-rod dystrophy-2 (adCRD2; refs 3, 4, 5), retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), which all lead to loss of vision. We generated mice carrying a targeted disruption of Crx. Crx-/- mice do not elaborate photoreceptor outer segments and lacked rod and cone activity as assayed by electroretinogram (ERG). Expression of several photoreceptor- and pineal-specific genes was reduced in Crx mutants. Circadian entrainment was also affected in Crx-/- mice.

Animals↗
PubMed1999

Generation of bcr-abl specific cytotoxic T-lymphocytes by using dendritic cells pulsed with bcr-abl (b3a2) peptide: its applicability for donor leukocyte transfusions in marrow grafted CML patients.

Dendritic cells (DC), the most potent 'professional' antigen-presenting cells, hold promise for improving the immunotherapy of cancer. In this study, we investigated the ability of normal donor DC pulsed ex vivo with 12 mer bcr-abl (b3a2) peptide to generate b3a2-specific autologous or HLA-identical sibling donor's cytotoxic T-lymphocytes (CTL). DC that were grown from normal peripheral blood adherent cells or purified DC precursors in the presence of GM-CSF and IL-4, were pulsed with b3a2-peptide then were induced to become mature and functional cells by the addition of TNF-alpha. These peptide-pulsed mature DC elicited a potent b3a2-specific CTL response in vitro. The b3a2-peptide pulsed DC-primed peripheral blood lymphocytes (PBL) displayed significantly higher cytotoxic activity compared with peptide non-pulsed DC-primed PBL against target cells, which are b3a2 positive marrow cells derived from HLA-identical sibling chronic myelogenous leukemia (CML) patient, or peptide-pulsed autologous macrophages (P < 0.001). In addition, the b3a2 peptide-pulsed DC-primed and non-pulsed DC-primed PBL showed no cytotoxic response against peptide non-pulsed autologous macrophages. These findings revealed that normal donor PBL pre-immunized with b3a2-peptide pulsed autologous DC could increase the graft-versus-leukemia effect without exaggerating graft-versus-host-disease. Both CD8+ and CD4+ T lymphocytes were shown to be involved in the effector cell populations. The b3a2 peptide-pulsed DC-primed T cells were significantly superior in their production of GM-CSF and TNF-alpha compared with peptide non-pulsed DC-primed T cells. These intriguing preclinical results imply the feasibility of developing b3a2 peptide-DC based protocol for in vitro sensitization of normal donor leukocytes before donor leukocyte transfusions for patients with CML, who relapsed after HLA-matched sibling bone marrow transplantation.

Blood Donors↗
PubMed1999

Effect of B7.1-transfected human colon cancer cells on the induction of autologous tumour-specific cytotoxic T cells.

BACKGROUND: The induction of tumour-specific immunity is important for advanced cancer therapy. There are many molecules, including costimulatory molecules, that have been identified as the activator for tumour-specific T cells. METHODS: To induce autologous tumour-specific cytotoxic T lymphocytes (CTL) more effectively, we studied whether the expression of the B7 gene may render human colon cancer cells able to stimulate autologous peripheral blood mononuclear cells (PBMC) to become tumour-specific cytotoxic T cells. After the establishment of a B7.1 gene transfected tumour cell line, Cw2/B7.1, we first examined its stimulatory effect on autologous PBMC and subsequently, its effect on the induction of parental cell (Cw2)-specific CTL. RESULTS: The results showed that Cw2/B7.1 had a more potent stimulatory effect on PBMC for the induction of both proliferation and cytotoxicity than Cw2. By adding a low dose of interleukin-2, Cw2/B7.1-activated killer cell activity was significantly increased. The specificity of Cw2/B7.1-activated killer cells was demonstrated by the absence of their cytotoxicity to either human lymphocyte antigen (HLA)-A33 identical (ORF) or HLA-non-identical (MT) allogenic colon cancer cell lines. Furthermore, such Cw2-specific cytotoxic activity was significantly reduced by the deletion of CD8+ cells but not CD4+ cells, indicating that these killer cells were mainly CD8+ T cells. CONCLUSIONS: Thus, our results demonstrate that, by using B7.1 gene-transfected tumour cell lines, we effectively induced autologous tumour-specific CTL. These results will provide us with new tools for adoptive immunotherapy for colon cancer patients.

B7-1 Antigen↗
PubMed1999

Infrequent somatic mutations of the p73 gene in various human cancers.

AIMS: It has already been reported that loss of heterozygosity (LOH) on chromosome 1p is frequent in a variety of human cancers. This finding implies the presence of some important tumour suppressor genes in this region. p73, a candidate tumour suppressor gene identified recently in chromosome band 1p36.33, encodes a protein highly homologous to p53. To investigate the role of the p73 gene in human carcinogenesis, we studied genetic alterations of this gene in various human cancers. METHODS: We analysed the entire coding exons as well as their surrounding exon-intron boundaries of the p73 gene in 185 cases of various types of tumours (47 breast cancers, 43 colorectal cancers, 31 gastric cancers, 23 neuroblastomas, 21 lung cancer cell lines, and 20 pancreatic cancer cell lines); they are known as a group of tumours with frequent LOHs in the 1p region. PCR-SSCP analysis was performed and tumours in which aberrant migrating sized bands were observed were subjected to direct sequencing analyses. RESULTS: Of the 185 cases, only one somatic mis-sense mutation of glutamine from arginine at codon 269 in exon 7 was found in one breast cancer. In addition, several polymorphisms were found at codons 137, 336, 349, and 610, as well as in introns 6, 8, and 9. Monoallelic expression was also observed in pancreatic cancer cell lines. CONCLUSIONS: Our results suggest that inactivation of the p73 gene does not play a major role in the tumour types analysed in the present study.

Alleles↗
PubMed1999

Possible involvement of central C-type natriuretic polypeptide receptor on water intake in spontaneously hypertensive rats, but not in normotensive Wistar-Kyoto rats.

The present study was designed to examine the possible role of brain C-type natriuretic polypeptide receptor (GC-B) in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY). The level of GC-B mRNA in various regions of the brain in both SHR and WKY was examined in the present study. The GC-B mRNA was unevenly distributed in rat brain, the transcript being expressed predominantly in the hypothalamus and cerebellum but comparatively at low level in the striatum and septum. However, the level in the septum was 3-fold higher in SHR than than in age-matched WKY, while no differences were observed in other regions of the brain. Intracerebroventricular administration of antisense oligonucleotide to GC-B mRNA inhibits the night-time water intake in SHR, but not in WKY. However, the daily food intake was not significantly altered by the injection of antisense oligonucleotide in both strains. These results demonstrate that the brain GC-B mRNA, particularly in septum, is increased in SHR and this increase may be closely related to the regulation of water-drinking behaviour in SHR.

Animals↗
PubMed1999

Toward artificial ribonucleases: design and synthesis of 2'-O-methyloligonucleotides with a terpyridine-copper(II) complex.

In order to construct an antisense 2'-O-methyloligonucleotide with an internal terpyridine-Cu(II) complex, a novel synthon was synthesized. This synthon was a 2'-deoxy-uridine-3'-phosphoramidite derivative with a terpyridine group at the 5'-O and a dimethoxytritylated hydroxypropyl group at the C-5. The antisense agent cleaved the RNA site-specifically and in a moderate yield.

Base Sequence↗
PubMed1999

Involvement of SHP-1, a phosphotyrosine phosphatase, during myeloid cell differentiation in acute promyelocytic leukemia cell lines.

We investigated the modulation of the expression and phosphatase activity of SHP-1 during granulocytic differentiation of human myeloid leukemia cell line, HL60 and t(15;17) positive APL cell line, HT93, in response to all-trans retinoic acid (ATRA) or dimethylsulfoxide (DMSO). ATRA induced differentiation in both cell lines which was associated with marked growth inhibition and S-phase reduction. On the other hand, DMSO induced it only in HL60 without obvious growth inhibition and S-phase reduction. The expression and phosphatase activity of SHP-1 were upregulated only when the 2 cell lines were differentiated to granulocytes. Furthermore, the changes were not dependent on the inducers or the growth inhibition. These findings suggest that SHP-1 is involved in common myeloid differentiation, and that upregulation of SHP-1 is not always related to myeloid cell growth.

Cell Cycle↗
PubMed1999

[Bacteriological studies of traveller's diarrhoea (6). Analysis of enteropathogenic bacteria at Kansai Airport Quarantine Station from September 4th, 1994 through December 1996].

During the period of investigation from Sept. 4, 1994 to Dec, 1996, a total of 11,446,534 overseas travellers were quarantined at Kansai Airport Quarantine Station, and 22,187 voluntarily reported of episodes suffering from diarrhoea. Bacteriological examination of the stools a total of 9,299 individuals' was performed, and the following results were obtained. 1) Various enteropathogenic bacteria were isolated from 33.3% of the stools examined. Bacterial species isolated were as follows: Plesiomonas shigelloides, 2,066 cases (66.7%); Vibrio parahaemolyticus, 358 cases (11.6%); Aeromonas sobria, 360 cases (11.6%); Shigella spp., 291 cases (9.4%); Salmonella spp., 183 cases (5.9%); A. hydrophila, 126 cases (4.1%); and V. cholerae non-O1, 121 cases (3.9%). However, ETEC was not done with an object of test. 2) In 502 cases (16.2%), plural enteropathogenic bacteria were isolated from single patient, suggesting high frequency of a mixed infections. 3) From Feb. to Mar. 1995, thirteen cases cholera were found from patients who had travelled to Bali, Indonesia. Cases with enteropathogenic bacteria other than V. cholerae O1 were found without any seasonal variation. 4) The major regions where the travellers were infected with the pathogens are as follows: Vibrio spp., were from only Asia; Shigella, widely distributed but especially in India and Indonesia; P. shigelloides and Salmonella, widely distributed. 5) Among the Shigella strains, S. sonnei were isolated the most, followed by S. flexneri, S. boydii and S. dysenteriae. A strain of S. boydii provisional serovar E 16553 was isolated from a patient infected in India. 6) Among the Salmonella serovars, Salmonella Enteritidis was isolated the most frequently (49 cases, 25.7%). 7) 265 (89.2%) of 297 Shigella strains, 52 (27.2%) of 19] Salmonella strains, and 19 (95.0%) of 20 V. cholerae O1 were resistant to one or more drugs tested (SM. CP. TC. KM. ABPC. NA. OFLX). 8) All of the 20 V. cholerae O1 strains were Ogawa, E1 Tor. All of them were toxigenic strains. 9) The most frequently isolated serovar of V. parahaemolyticus was O3: K6. 89.8% of all V. parahaemolyticus strains were positive for thermostable direct hemolysin (TDH) gene, and 14.6% of them were positive for TDH-related hemolysin (TRH) gene by DNA-probe or PCR method.

Asia, Southeastern↗
PubMed1999

Effect of multidrug resistance-reversing agents on transporting activity of human canalicular multispecific organic anion transporter.

The canalicular multispecific organic anion transporter (cMOAT), also termed MRP2, is a recently identified ATP-binding cassette transporter. We previously established stable human cMOAT cDNA-transfected cells, LLC/cMOAT-1 from LLC-PK1 cells, and LLC/CMV cells that were transfected with an empty vector. We found that LLC/cMOAT-1 cells have increased resistance to vincristine (VCR), 7-ethyl-10-hydroxy-camptothecin, and cisplatin but not to etoposide. The multidrug resistance-reversing agents cyclosporin A (CsA) and 2-[4-(diphenylmethyl)-1-piperazinyl]-5-(trans-4,6-dimethyl-1,3, 2-dioxaphosphorinan-2-yl)-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate P-oxide (PAK-104P) almost completely reversed the resistance to VCR, 7-ethyl-10-hydroxy-camptothecin, and cisplatin of LLC/cMOAT-1 cells; and DL-buthionine-(S,R)-sulfoximine, (3'-oxo-4-butenyl-4-methyl-threonine(1), (valine(2)) cyclosporin (PSC833), and 3-([(3-(2-[7-chloro-2-quinolinyl]ethenyl)phenyl)-((3-dimethylamino-3- oxopropyl)-thio)-methyl]thio)propanoic acid (MK571) partially reversed the resistance to these drugs. CsA and PAK-104P at 10 microM enhanced the accumulation of VCR in LLC/cMOAT-1 cells almost to the level in LLC/CMV cells without the agents. The efflux of VCR from LLC/cMOAT-1 cells was enhanced compared with LLC/CMV cells and inhibited by CsA and PAK-104P. Transport of leukotriene C(4) (LTC(4)) and S-(2, 4-dinitrophenyl)glutathione also was studied with membrane vesicles prepared from these cells. LTC(4) and S-(2, 4-dinitrophenyl)glutathione were actively transported into membrane vesicles prepared from LLC/cMOAT-1 cells. The K(m) and V(max) values for the uptake of LTC(4) by the LLC/cMOAT-1 membrane vesicles were 0. 26 +/- 0.05 microM and 7.48 +/- 0.67 pmol/min/mg protein, respectively. LTC(4) transport was competitively inhibited by PAK-104P, CsA, MK571, and PSC833, with K(i) values of 3.7, 4.7, 13.1, and 28.9 microM, respectively. These findings demonstrate that cMOAT confers a novel drug-resistance phenotype. CsA and PAK-104P may be useful for reversing cMOAT-mediated drug resistance in tumors.

Adenosine Triphosphate↗
PubMed1999

NeuroD regulates multiple functions in the developing neural retina in rodent.

The expression and function of the basic helix-loop-helix (bHLH) transcription factor NeuroD were studied in the developing neural retina in rodent. neuroD was expressed in areas of undetermined retinal cells as well as developing photoreceptors and amacrine interneurons. Expression was maintained in a subset of mature photoreceptors in the adult retina. Using both loss-of-function and gain-of-function approaches, NeuroD was found to play multiple roles in retinal development. (1) NeuroD was found to be a critical regulator of the neuron versus glial cell fate decision. Retinal explants derived from NeuroD-null mice demonstrated a three- to fourfold increase in Müller glia. Forced expression of neuroD in progenitors in rat using retroviruses hastened cell cycle withdrawal and blocked gliogenesis in vivo. (2) NeuroD appeared to regulate interneuron development, favouring amacrine over bipolar differentiation. Forced NeuroD expression resulted in an increase in amacrine interneurons and a decrease in bipolar interneurons. In the complementary experiment, retinae derived from NeuroD-null mice demonstrated a twofold increase in bipolar interneurons and a delay in amacrine differentiation. (3) NeuroD appeared to be essential for the survival of a subset of rod photoreceptors. In conclusion, these results implicate NeuroD in a variety of developmental functions including cell fate determination, differentiation and neuron survival.

Animals↗
PubMed1999

Detection of abnormal high-frequency components in the QRS complex by the wavelet transform in patients with idiopathic dilated cardiomyopathy.

In order to investigate whether increased fine, fractionated signals within the QRS complex can detect arrhythmogenic substrates and how these fine signals link with ventricular mechanical dysfunction, wavelet analysis was performed on averaged QRS complexes obtained from the left precordial lead in 26 patients with idiopatic dilated cardiomyopathy (IDCM) and in 12 normal subjects. The number of local maxima and the duration of the wavelet transform were significantly greater in patients with IDCM than in normal subjects; the number at 100 Hz was 8.8+/-3.1 vs 6.0+/-1.1 (p<0.01), and the duration at 100Hz was 93+/-15 vs 75+/-7ms (p<0.01). Both of these indices were greater in the patients with than in those without late potentials, repetitive ventricular premature beats or cardiac death. In addition, significant inverse curvilinear relationships were observed between the left ventricular ejection fraction and both the number of local maxima and the duration of the wavelet transform. In conclusion, fine fragmented signals in the QRS complex detected by wavelet analysis would be an important marker for potentially arrhythmogenic substrates and seemed to progress in parallel with left ventricular mechanical dysfunction in IDCM.

Adolescent↗
PubMed1999

A prospective multicenter trial evaluating diagnostic validity of multivariate analysis and individual serum marker in differential diagnosis of pancreatic cancer from benign pancreatic diseases.

CONCLUSION: A multivariate analysis of CAMPAS-PX2 can increase its diagnostic accuracy in differential diagnosis of pancreatic cancer from benign pancreatic or extrapancreatic disease, when compared with CA19-9 alone. However, the improvement in diagnostic accuracy is still not satisfactory in spite of an elaborate combination of serum markers in diagnosis for pancreatic cancer. Optimal combination of a sensitive serum marker and another diagnostic modality, such as ultrasonography, can be a practical way to improve important diagnostic and cost-effectiveness in diagnosis for pancreatic cancer. BACKGROUND: No specific biological test has yet been developed for diagnosis of pancreatic cancer, although increasing numbers of tumor markers become available. For improvement in the diagnostic and cost effectiveness, it is important to select optimal combination of several serum markers relatively independent of each other. METHODS: A new model of discriminant function, computer-aided multivariate and pattern analysis system for pancreatic cancer examination 2 (CAMPAS-PX2), was developed based on the data of the 23 serum tumor markers from the first prospective trial (1) to differentiate between pancreatic cancer and benign pancreatobiliary disease by logistic regression analysis using a stepwise selection method. In 243 patients suspected of having pancreatic pancreatic cancer by a multicenter prospective study, the diagnostic value of the multivariate analysis, CAMPAS-PX2, was compared with the 23 markers. RESULTS: Pancreatic cancer was subsequently identified in 27 patients. Positive in disease, negative in health, and area under receiver operating characteristic curve were significantly higher by CAMPAS-PX2 (89, 87, 91%) than by CA 19-9 (78, 82, 84%), the most sensitive marker among the 23 markers.

Biomarkers, Tumor↗
PubMed1999

Genomic analysis of the thymine-DNA glycosylase (TDG) gene on 12q22-q24.1 in human pancreatic ductal adenocarcinoma.

CONCLUSION: Abnormality of the thymine-DNA glycosylase (TDG) gene on 12q22-q24.1 appears to play a limited role in pancreatic ductal carcinogenesis. BACKGROUND: Recently, a human G/T-specific TDG gene was identified. This protein acts in a system correcting G/T mispairs to G/C pairs. TDG was mapped to chromosome bands 12q22-q24.1, one of the regions frequently lost in pancreatic cancer. Therefore, there is the possibility that the TDG gene on 12q is one of the genes responsible for pancreatic ductal carcinogenesis. METHODS: Nucleotide sequences of the entire coding region of the TDG gene were analyzed in 21 human pancreatic cancer cell lines. mRNA expression of the TDG gene was also analyzed by Northern hybridization in several human tissues and 21 human pancreatic cancer cell lines. RESULTS: Decreased levels of mRNA expression were detected in the pancreatic cancer cell lines, but no somatic mutations were observed.

Adenocarcinoma↗