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Biomedical subjects

K Tanimoto

Publications and source records attributed to K Tanimoto.

At least 55 records · Page 3Linked to original sources
PubMed2000

Amino acid substitutions in the VanS sensor of the VanA-type vancomycin-resistant Enterococcus strains result in high-level vancomycin resistance and low-level teicoplanin resistance.

The vancomycin-resistant enterococci GV1, GV2 and GV3, which were isolated from droppings from broiler farms in Japan have been characterized as VanA-type VRE, which express high-level vancomycin resistance (256 or 512 microg ml(-1), MIC) and low-level teicoplanin resistance (1 or 2 microg ml(-1), MIC). The vancomycin resistances were encoded on plasmids. The vancomycin resistance conjugative plasmid pMG2 was isolated from the GV2 strain. The VanA determinant of pMG2 showed the same genetic organization as that of the VanA genes encoded on the representative transposon Tn1546, which comprises vanRSHAXYZ. The nucleotide sequences of all the genes, except the gene related to the vanS gene on Tn1546, were completely identical to the genes encoded on Tn1546. Three amino acid substitutions in the N-terminal region of the deduced VanS were detected in the nucleotide sequence of vanS encoded on pMG2. There were also three amino acid substitutions in the vanS gene of the GV1 and GV3 strains in the same positions as in the vanS gene of pMG2. Vancomycin induced the increased teicoplanin resistance in these strains.

Amino Acid Sequence↗
PubMed2000

Beta-globin YAC transgenes exhibit uniform expression levels but position effect variegation in mice.

Expression of a construct integrated at different genomic locations often varies because of position effects that have been subcategorized as stable (decreased level of expression) and variegating (decreased proportion of expressing cells). It is well established that locus control regions (LCRs) generally overcome position effects in transgenes. However, whether stable and variegated position effects are equally overcome by an intact LCR has not been determined. We report that single-copy yeast artificial chromosome transgenes containing an unmodified human beta -globin locus were not subject to detectable stable position effects but did undergo mild to severe variegating position effects at three of the four non-centromeric integration sites tested. We also find that, at a given integration site, the distance and the orientation of the LCR relative to the regulated gene contributes to the likelihood of variegating position effects, and can affect the magnitude of its transcriptional enhancement. DNase I hypersensitive site (HSS) formation varies with the proportion of expressing cells, not the level of gene expression, suggesting that silencing of the transgene is associated with a lack of HSS formation in the LCR region. We conclude that transcriptional enhancement and variegating position effects are caused by fundamentally different but inter-dependent mechanisms.

Animals↗
PubMed2000

Absence of CD83-positive mature and activated dendritic cells at cancer nodules from patients with hepatocellular carcinoma: relevance to hepatocarcinogenesis.

Mature and activated dendritic cells (CD83-positive DCs) are essential for the recruitment and survival of activated tumor-specific lymphocytes during carcinogenesis. The frequencies of CD83 positive DCs were almost same in peripheral blood from patients with hepatocellular carcinoma (HCC) and cirrhosis of liver (LC). However, the numbers of CD83 positive DCs in liver tissues were significant lower in HCC compared with LC (6.6+/-10.9 vs. 33.3+/-24 DCs/specimen, P<0.05). Most importantly, there were no CD83-positive DCs at cancer nodules in HCC. A role of infiltration of activated DCs in liver during hepatocarcinogenesis is shown.

Antigens, CD↗
PubMed2000

In vivo modulation of human beta-globin gene switching.

Continuing accumulation of information from the genome projects requires parallel development of technologies to assess the in vivo functions of conserved sequences. We can now manipulate huge DNA molecules (such as yeast artificial chromosomes; YACs) in vivo, permitting the analysis of very large single genes or multigene loci as they exist in the chromosome. However, since transgenes integrate randomly into different chromatin environments, accurate evaluation of gene function in such transgenic mice is still fraught with pitfalls. We recently developed the use of cre-mediated homologous recombination to manipulate YAC transgenic mice in vivo, and successfully applied this strategy to the analysis of human beta-globin locus regulation. Here we describe these results and discuss the application of this technology to the analysis of this and related problems.

Animals↗
PubMed2000

A cineradiographic study of deglutitive tongue movement and nasopharyngeal closure in patients with anterior open bite.

The purpose of this study was to investigate the movement of the tip and the dorsal surface of the tongue during deglutition in patients with anterior open bite using cineradiography. The subjects were 10 female patients with anterior open bites and 10 female controls with normal overbites. By cineradiography we established 7 stages of tongue movement and bolus position during deglutition and analyzed the tongue position, tongue movement and the time. The tongue-tip position was more protrusive during deglutition in anterior open bite than in the controls. After the head of the bolus arrived at the opening of the esophagus, the rear part of the dorsal surface of the tongue demonstrated slower movement in patients with anterior open bite than in controls. The nasopharynx closed earlier in patients with anterior open bite than in controls. It is suggested that anterior open bite patients had compensatory coordination of tongue movement, soft palate movement and pharyngeal constrictor muscle activity during deglutition.

Adolescent↗
PubMed2000

Abnormalities of the FHIT gene in human oral carcinogenesis.

The abnormalities of the fragile histidine triad (FHIT) gene in tissue samples of oral squamous cell carcinomas (SCCs) along with several leukoplakias and an erythroplakia were examined to determine whether the FHIT gene is actually a frequent target in vivo for alteration during oral carcinogenesis. Abnormal transcripts of the FHIT gene were found in eight of 15 oral SCCs. Although these abnormal transcripts varied widely, deletion patterns incorporating a deletion of exon 5 were the most common. Loss of heterozygosity (LOH) analysis demonstrated that the abnormal FHIT transcripts found in cancer cells were attributable to abnormalities of the FHIT gene. Abnormal FHIT transcripts were also observed in two of seven premalignant lesions. Interestingly, in the case of one patient with a premalignant lesion showing an abnormal FHIT transcript, subsequent oral SCC developed during a 3-year follow-up period. On the other hand, in the two patients from whom both leukoplakia and SCC samples were taken simultaneously, abnormal FHIT transcripts were found only in the SCCs. Although the functional role of FHIT remains to be clarified, these results suggest that the FHIT alteration is actually involved in carcinogenesis of the oral epithelium.

Acid Anhydride Hydrolases↗
PubMed2000

The effects of high magnitude cyclic tensile load on cartilage matrix metabolism in cultured chondrocytes.

Excessive mechanical load is thought to be responsible for the onset of osteoarthrosis (OA), but the mechanisms of cartilage destruction caused by mechanical loads remain unknown. In this study we applied a high magnitude cyclic tensile load to cultured chondrocytes using a Flexercell strain unit, which produces a change in cell morphology from a polygonal to spindle-like shape, and examined the protein level of cartilage matrixes and the gene expression of matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs) and proinflammatory cytokines such as IL-1beta and TNF-alpha. Toluidine blue staining, type II collagen immunostaining, and an assay of the incorporation of [35S]sulfate into proteoglycans revealed a decrease in the level of cartilage-specific matrixes in chondrocyte cultures subjected to high magnitude cyclic tensile load. PCR-Southern blot analysis showed that the high magnitude cyclic tensile load increased the mRNA level of MMP-1, MMP-3, MMP-9, IL-1beta, TNF-alpha and TIMP-1 in the cultured chondrocytes, while the mRNA level of MMP-2 and TIMP-2 was unchanged. Moreover, the induction of MMP-1, MMP-3 and MMP-9 mRNA expression was observed in the presence of cycloheximide, an inhibitor of protein synthesis. These findings suggest that excessive mechanical load directly changes the metabolism of cartilage by reducing the matrix components and causing a quantitative imbalance between MMPs and TIMPs.

Animals↗
PubMed2000

Distinct mechanisms of loss of estrogen receptor alpha gene expression in human breast cancer: methylation of the gene and alteration of trans-acting factors.

We have previously shown that the distal promoter (promoter B) of the estrogen receptor alpha (ER alpha) gene is responsible for the enhanced expression of the ER alpha gene seen in human breast cancer and that a novel trans-acting factor, estrogen receptor promoter B associated factor 1 (ERBF-1), is required for transcription from promoter B in breast cancer cells. In development of breast cancer, loss of ER alpha gene expression is one of the most important steps in acquiring hormone resistance, though the mechanisms are poorly understood. Recent studies have reported that methylation of the ER alpha gene promoter A and exon 1 was inversely associated with ER alpha gene expression in human breast cancer and cell lines. The methylation status of the promoter B region, which is responsible for overexpression of ER alpha protein in cancer tissue, has not been investigated. In this report, we found that the methylation status of promoter B, as well as that of promoter A, was inversely associated with ER alpha gene expression in human breast cancer and cell lines. Specific methylation of ER alpha gene promoters in vitro directly decreased transcription of the ER alpha gene in a reporter assay. Demethylating treatment induced transcription of ER alpha mRNA from promoter B in ZR-75-1 cells, which showed no transcription from promoter B, despite weak ERBF-1 expression, but not in ER alpha-negative MDA-MB-231 and BT-20 cells, which lack ERBF-1. ZR-75-1 cells showed promoter activity equal to that of MCF-7 cells in a reporter assay. Our results indicate that methylation of promoter B of the ER alpha gene is important for loss of ER alpha gene expression in human breast cancer, and methylation of the promoters can directly modulate ER alpha gene expression. However, loss of critical transcriptional factors such as ERBF-1 may also be involved in some ER alpha-negative cases.

Base Sequence↗
PubMed2000

Degos' disease with constrictive pericarditis: a case report.

A 47-year-old man with Degos' disease was examined by echocardiography, which showed hypokinesis of the apical left ventricular wall with pericardial effusion. To evaluate the myocardial perfusion and coronary flow reserve, 201Tl scintigraphy and intracoronary Doppler flowmetry were performed. The coronary flow reserve was not decreased nor was there angiographical coronary stenosis, although a pressure study revealed constrictive dysfunction of both ventricles. The constrictive pericarditis might have been induced by pericardial vasculitis, thereby causing the left ventricular wall motion abnormality.

Humans↗
PubMed2000

[A case of fixed drug eruption due to ephedrine hydrochloride].

We report the case of a 29-year old female who developed a fixed drug eruption due to ephedrine hydrochloride administered intravenously during the cesarean section. On the day of the operation a palm-sized dark brown macula with half egg-sized erosion appeared on her right lower thigh. We diagnosed her disease as fixed drug eruption and examined the causative agent among all the 14 drugs used from admission to the appearance of fixed drug eruption. Each of systemic challenge, patch test on the lesion, intradermal and subcutaneous injection on the lesion with ephedrine hydrochloride showed positive reaction. As far as we have been able to search, our case is the first one of fixed drug eruption due to ephedrine hydrochloride.

Adult↗
PubMed2000

[Psoriatic arthritis].

Explore the source record for details and available documents.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

The polyoma virus enhancer cannot substitute for DNase I core hypersensitive sites 2-4 in the human beta-globin LCR.

The polyoma virus enhancer (PyE) is capable of conferring integration position-independent expression to linked genes in stably transfected erythroid cells after joining to DNase I hypersensitive site (HS) 5 of the human beta-globin locus control region (LCR). In attempting to separate the chromatin opening activity of the LCR from its enhancer activity and to investigate contributions of the individual HS core elements to LCR function, the human beta-globin LCR HS2, HS3 and HS4 core elements were replaced with the PyE within the context of a yeast artificial chromosome (YAC) bearing the whole locus. We show here that, in contrast to its function in cultured cells, the PyE is unable to replace HS core element function in vivo. We found that the PyE substitution mutant LCR is unable to provide either chromatin opening or transcriptional potentiating activity at any erythroid developmental stage in transgenic mice. These data provide direct evidence that the human beta-globin LCR core elements specify unique functions that cannot be replaced by a ubiquitous enhancer activity.

Animals↗
PubMed1999

Male sterility in transgenic mice expressing activin betaA subunit gene in testis.

Activins and inhibins, which are endocrine regulators of anterior pituitary function, have also been reported to participate in the paracrine and autocrine regulation of reproductive function. To determine the in vivo effects of overexpressed activin/inhibin, we generated transgenic mice carrying the human activin/inhibin betaA subunit mini gene under the regulatory control of the mouse methallothionein promoter. In one of the transgenic line analyzed, the betaA subunit gene was preferentially expressed in the testis. Ectopic and allochronic expression of the betaA gene started at 3 weeks after birth and transgenic male mice became sterile in the ensuing several weeks. Histological analysis revealed testicular degeneration in these mice. The results from this transgenic line strongly support the in vivo activity of activin/inhibin in male reproductive functions.

Animals↗
PubMed1999

Unique features of dendritic cells in IFN-gamma transgenic mice: relevance to cancer development and therapeutic implications.

Although induction of interferon gamma (IFN-gamma) and activation of antigen presenting dendritic cells (DCs) are two vital events during an immune response, the impact of endogenous IFN-gamma on DC function has yet to be clarified. The phenotype and function of DCs isolated from mice with high (IFN-gamma-transgenic mouse [Tg]) and undetectable levels of circulating IFN-gamma (normal mice [NM]) were therefore compared. The capacity to stimulate allogenic (p < 0.05) and antigen-specific T lymphocytes (p < 0.05), as well as the ability to produce IL-12 (p < 0.05) and to process soluble protein antigens (p < 0.05) was found to be significantly higher in DCs from the Tg mice compared to the NM case. The presence of activated DCs in a microenvironment of endogenous IFN-gamma suggests that the IFN-gamma-Tg mouse is a suitable animal model to study cancer immunotherapy in vivo.

Animals↗