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Biomedical subjects

T Tsuji

Publications and source records attributed to T Tsuji.

At least 217 records · Page 12Linked to original sources
PubMed2000

Greater than normal expression of the collagen-binding stress protein heat-shock protein-47 in the infarct zone in rats after experimentally-induced myocardial infarction.

BACKGROUND: The heat-shock protein with relative molecular mass 47,000 (HSP47) can bind to procollagen molecules in the endoplasmic reticulum, and acts as a molecular chaperone during the processing and secretion of procollagen. OBJECTIVE: To test our hypothesis that HSP47 is expressed in the myocardial infarct zone. METHODS: We induced myocardial infarction in male Sprague-Dawley rats by ligation of left coronary artery. The expression of HSP47 was examined by Northern blotting, in-situ hybridization, Western blotting and immunohistochemistry. The time-dependent change in the distribution of HSP47 messenger RNA (mRNA) signal was compared with the changes in expression of alpha 1(I) and alpha 1(III) collagen mRNA by in-situ hybridization. The hypoxic induction of HSP47 in cultured cardiac fibroblasts was examined by Northern-blot analysis. RESULTS: Northern blotting demonstrated that the expression of HSP47 mRNA had increased on day 2, reaching a maximum level around day 14 (induced 3.5-fold compared with the preligation hearts) and was maintained at a high level up to day 28. In-situ hybridization analysis revealed HSP47 mRNA signals in spindle-shaped mesenchymal cells located between surviving myocytes in the infarct's peripheral zone 24 h after the ligation, and in the entire infarct zone on day 14. The sequential changes in distribution of HSP47 mRNA signal were identical to those of the alpha 1(I) and alpha 1(III) collagen mRNA. Western blotting demonstrated that expression of HSP47 protein in the infarct zone had increased. Immunofluorescent staining revealed positivity for HSP47 in the infarct's peripheral zone on day 2 and in the entire infarct zone on day 14. Northern blotting revealed that the expression of HSP47 mRNA in cultured cardiac fibroblasts in hypoxic cultures was greater than that in normoxic cultures. CONCLUSION: The present data demonstrated that an increase in expression of HSP47 is produced by spindle-shaped mesenchymal cells in the infarct zone. Expression of HSP47 mRNA was concurrent with the expression of collagen mRNA of types I and III. Hypoxia is one of the factors which induces expression of HSP47.

Animals↗
PubMed2000

Effect of long range order on sheared liquid crystalline materials: flow regimes, transitions, and rheological phase diagrams

A generalized theory that includes short-range elasticity, long-range elasticity, and flow effects is used to simulate and characterize the shear flow of liquid crystalline materials as a function of the Deborah (De) and Ericksen (Er) numbers in the presence of fixed planar director boundary conditions; the results are also interpreted as a function of the ratio R between short-range and long-range elasticity. The results are effectively summarized into rheological phase diagrams spanned by De and Er, and also by R and Er, where the stability region of four distinct flow regimes are indicated. The four regimes for planar (two-dimensional orientation) shear flow are (1) the elastic-driven steady state, (2) the composite tumbling-wagging periodic state, (3) the wagging periodic state, and (4) the viscous-driven steady state. The coexistence of the four regimes at a quacritical point is shown to be due to the emergence of a defect structure. The origin, the significant steady and dynamical features, and the transitions between these regimes are thoroughly characterized and analyzed. Quantitative and qualitative comparisons between the present complete model predictions and those obtained from the classical theories of nematodynamics (Leslie-Ericksen and Doi theories) are presented and the main physical mechanisms that drive the observed deviations between the predictions of these models are identified. The presented results fill the previously existing gap between the classical Leslie-Ericksen theory and the Doi theory, and present a unified description of nematodynamics.

Journal Article↗
PubMed2000

Effect of erythromycin on Shigella infection of Caco-2 cells.

Erythromycin (EM), one of the macrolides, shows a dose-dependent effect on Shigella flexneri invasion of Caco-2 cells even at concentrations less than the minimum inhibitory concentration (subMIC). LS13, a strain of S. flexneri 1b, invaded Caco-2 cells in vitro. When the strain was treated with subMIC of EM, the invasion efficiency decreased. The carrier rate of the invasion plasmid containing virulence genes was reduced by EM treatment, as determined by the colony pigmentation test on Congo red agar plates. Presence of the invasion plasmid was found to increase susceptibility of the organisms to EM. The growth of virulent organisms carrying the invasion plasmid was inhibited at 25 microg ml(-1) of EM, whereas the growth of organisms without the plasmid was inhibited at 100 microg ml(-1) of EM. This was supported by the finding that the MIC of EM for a virulent isolate of S. flexneri 2a YSH6000 (6.25 microg ml(-1)) and for the mutant strain del-17 (50 microg ml(-1)), carrying the type III apparatus, impaired plasmid. These findings suggested that EM passed through the type III apparatus and suppressed the growth of invasive organisms selectively. This mechanism may account for the clinical effect of EM on shigellosis.

Anti-Bacterial Agents↗
PubMed2000

Antibody to heat shock protein can be used for early serological monitoring of Helicobacter pylori eradication treatment.

Infection with Helicobacter pylori induces humoral immune responses against various antigens of the bacterium. Heat shock proteins (hsps) are immunodominant antigens in various diseases including H. pylori infection. In the present study, we measured the anti-hsp antibody titers in 42 patients with H. pylori-infected peptic ulcers during a bacterial eradication study. The patients were treated with a proton pump inhibitor and antimicrobial agents to eradicate the organism. Their sera were obtained at pretreatment and at 1 month and 6 months after the eradication therapy. The titers of immunoglobulin G antibodies to the H. pylori hsp, whole-cell lysate, and urease (30-kDa subunit) antigens in serum were measured by a capture enzyme-linked immunosorbent assay. The levels of H. pylori hsp60 antibodies in sera collected 1 month after treatment had declined significantly, even when changes in the titers of antibodies to whole-cell and urease antigens were not apparent. These results suggest that measurement of antibodies to H. pylori hsp60 in serum is useful for the early monitoring of the effectiveness of eradication therapy.

Adult↗
PubMed2000

p12(DOC-1) is a novel cyclin-dependent kinase 2-associated protein.

Regulated cyclin-dependent kinase (CDK) levels and activities are critical for the proper progression of the cell division cycle. p12(DOC-1) is a growth suppressor isolated from normal keratinocytes. We report that p12(DOC-1) associates with CDK2. More specifically, p12(DOC-1) associates with the monomeric nonphosphorylated form of CDK2 (p33CDK2). Ectopic expression of p12(DOC-1) resulted in decreased cellular CDK2 and reduced CDK2-associated kinase activities and was accompanied by a shift in the cell cycle positions of p12(DOC-1) transfectants ( upward arrow G(1) and downward arrow S). The p12(DOC-1)-mediated decrease of CDK2 was prevented if the p12(DOC-1) transfectants were grown in the presence of the proteosome inhibitor clasto-lactacystin beta-lactone, suggesting that p12(DOC-1) may target CDK2 for proteolysis. A CDK2 binding mutant was created and was found to revert p12(DOC-1)-mediated, CDK2-associated cell cycle phenotypes. These data support p12(DOC-1) as a specific CDK2-associated protein that negatively regulates CDK2 activities by sequestering the monomeric pool of CDK2 and/or targets CDK2 for proteolysis, reducing the active pool of CDK2.

Blotting, Western↗
PubMed2000

Activation of the dorsal premotor cortex and pre-supplementary motor area of humans during an auditory conditional motor task.

Using functional magnetic resonance imaging (fMRI), we measured regional blood flow to examine which motor areas of the human cerebral cortex are preferentially involved in an auditory conditional motor behavior. As a conditional motor task, randomly selected 330 or 660 Hz tones were presented to the subjects every 1. 0 s. The low and high tones indicated that the subjects should initiate three successive opposition movements by tapping together the right thumb and index finger or the right thumb and little finger, respectively. As a control task, the same subjects were asked to alternate the two opposition movements, in response to randomly selected tones that were presented at the same frequencies. Between the two tasks, MRI images were also scanned in the resting state while the tones were presented in the same way. Comparing the images during each of the two tasks with images during the resting state, it was observed that several frontal motor areas, including the primary motor cortex, dorsal premotor cortex (PMd), supplementary motor area (SMA), and pre-SMA, were activated. However, preferential activation during the conditional motor task was observed only in the PMd and pre-SMA of the subjects' left (contralateral) frontal cortex. The PMd has been thought to play an important role in transforming conditional as well as spatial visual cues into corresponding motor responses, but our results suggest that the PMd along with the pre-SMA are the sites where more general and extensive sensorimotor integration takes place.

Acoustic Stimulation↗
PubMed2000

Expression of Lewis(a), sialyl Lewis(a), Lewis(x) and sialyl Lewis(x) antigens as prognostic factors in patients with colorectal cancer.

BACKGROUND: Altered expression of blood group-related carbohydrate antigens such as sialyl Lewis (Le)(x) antigen in tumours is associated with tumour progression behaviour and subsequent prognosis. However, the prognostic value of the expression of Le-related antigens in colorectal tumours remains unclear. PURPOSE: To clarify the prognostic value of Le(a), sialyl Le(a), Le(x) and sialyl Le(x) expression in colorectal carcinomas as prognostic factors after surgery. PATIENTS AND METHODS: Colorectal carcinoma samples from 101 patients with primary colorectal carcinoma who underwent surgical resection were subject to immunohistochemical analyses for Lea, sialyl Lea, Lex and sialyl Le(x) expression with the respective monoclonal antibodies. RESULTS: Le(a), sialyl Le(a), Le(x) and sialyl Le(x) were expressed in 69 (68.3%), 73 (72.3%), 66 (65.4%) and 76 (75.3%) carcinomas, respectively. The patients with sialyl Lex-expressing tumours had more advanced cancer than those with nonsialyl Lex-expressing tumours (P=0.0029). The survival time after surgery of patients with Le(x)- or sialyl Le(x)-expressing tumours was significantly shorter than the survival time of those with non-Le(x)- or nonsialyl Le(x)-expressing tumours, respectively (P=0.023 and P=0. 0001, respectively). Cox's regression analysis revealed that Le(x) and sialyl Le(x) expression, separate from stage and histological type, were prognostic variables for patient survival (hazard ratio [HR] for sialyl Le(x)-positive expression to sialyl L(x)-negative expression 2.90; HR for Le(x)-positive expression to Le(x)-negative expression 12.76 in stage I/IV, 0.63 in stage II and 1.69 in stage III). CONCLUSIONS: Le(x) expression and sialyl Le(x) expression in colorectal carcinomas are each associated with poor prognosis. These variables should be considered in the design of future trials.

Colorectal Neoplasms↗
PubMed2000

HLA-DRB genotypes in Japanese patients with renal cell carcinoma.

OBJECTIVES: Several clinical features, such as the spontaneous regression of some renal cell carcinoma (RCC) metastases after nephrectomy, suggest immune involvement in tumor destruction. PATIENTS AND METHODS: We investigated the role of genetic variation at the HLA class II loci in RCC by analyzing the HLA-DR antigen and HLA-DRB1, DRB3, DRB4 and DRB5 alleles in 55 patients using the polymerase chain rection. RESULTS: No statistically significant differences were observed in the frequency of the HLA-DR antigen or HLA-DRB3, DRB4, or DRB5 genes between the patients and a healthy control group. On the other hand, the HLA-DRB1*0403 and *1202 alleles were significantly more frequent in the patients than in the controls (p < 0.001 and p < 0.01, respectively). CONCLUSION: RCC might be linked to these two alleles in Japanese patients.

Adult↗
PubMed2000

Videoendoscopic laryngeal surgery.

This paper introduces videoendoscope-assisted laryngeal surgery with office-based equipment. With this technique, a patient is seated and the nose, pharynx, and larynx are topically anesthetized. A flexible videoendoscope with a light-sensitive charge-coupled device chip built into the tip is transnasally inserted by an assistant. Specially designed fine-tipped forceps and scalpels were developed for removal of laryngeal lesions. Videoendoscopic laryngeal surgery was undertaken in 114 cases of laryngeal lesions such as polyps, granuloma, and cancer. For benign vocal fold lesions, postoperative vocal function was shown to be improved on aerodynamic and perceptual analyses. For laryngeal tumors, biopsy of the lesion was easily undertaken. Videoendoscopic laryngeal surgery presents the following advantages. It is applicable to outpatients not requiring general anesthesia, it enables functional monitoring of the patient's voice and vocal fold during phonation, it allows for delicate manipulations with both hands, and it gives high-resolution images in comparison to conventional fiberscopy.

Adult↗
PubMed2000

Mastoid pneumatization of the patulous eustachian tube.

The pathophysiology of the patulous eustachian tube (PET) remains unclear. The degree of mastoid cell pneumatization is considered an indicator of chronic inflammation of the middle ear. We used the mastoid cell area to investigate the relationship between past chronic inflammation of the middle ear cavity and a PET in 84 patients (20 to 83 years old). The mastoid cell size was calculated from radiographs and analyzed relative to the history of otitis media (OM). The controls were 100 normal ears. The patients' mastoid cell size was significantly suppressed versus that of the controls, in both 31 PET cases with and 53 PET cases without past OM. We surmise the possibility that the PET ears had experienced inflammation even when the patients had no history of OM and the tympanic membrane showed no OM sequelae. This study indicates the existence of some relationship between a history of chronic inflammation of the middle ear cavity and a PET.

Adult↗
PubMed2000

Age-related alterations in IL-1beta, TNF-alpha, and IL-6 concentrations in parotid acinar cells from BALB/c and non-obese diabetic mice.

IL-1beta, TNF-alpha, and IL-6 have been implicated in the destruction of parotid gland acinar cells (but not duct cells) in autoimmune sialoadenitis. Here we report the temporal alterations of these cytokines in parotid acinar cells that may lead to this specificity in cell death in the non-obese diabetic (NOD) mouse model for Sjögren's syndrome. Immunohistochemistry on paraffin sections of parotid gland from 5- and 10-week-old BALB/c and NOD mice confirmed the presence of many peri-acinar lymphoid nodules but few T-cells and macrophages between acinar cells. RT-PCR on enzymatically dispersed mouse parotid acinar cells (MPACs) showed no bands for CD3varepsilon, CD20, or F4/80 regardless of mouse strain or age. By ELISA, MPACs from 10-week-old NODs showed a small but highly significant (p<0.003) increase in IL-1beta and a large significant decrease (p<0.008) in IL-6 compared to 5-week-old NODs. Norepinephrine-stimulated amylase release from MPACs was not different regardless of mouse strain or age. These data show that alterations in acinar cell production of IL-1beta and IL-6 in aging NODs precede periductal lymphoid aggregates and acinar cell secretory dysfunction. (J Histochem Cytochem 48:1033-1041,2000)

Aging↗
PubMed2000

Requirements of Lim1, a Drosophila LIM-homeobox gene, for normal leg and antennal development.

During Drosophila leg development, the distal-most compartment (pretarsus) and its immediate neighbour (tarsal segment 5) are specified by a pretarsus-specific homeobox gene, aristaless, and tarsal-segment-specific Bar homeobox genes, respectively; the pretarsus/tarsal-segment boundary is formed by antagonistic interactions between Bar and pretarsus-specific genes that include aristaless (Kojima, T., Sato, M. and Saigo, K. (2000) Development 127, 769-778). Here, we show that Drosophila Lim1, a homologue of vertebrate Lim1 encoding a LIM-homeodomain protein, is involved in pretarsus specification and boundary formation through its activation of aristaless. Ectopic expression of Lim1 caused aristaless misexpression, while aristaless expression was significantly reduced in Lim1-null mutant clones. Pretarsus Lim1 expression was negatively regulated by Bar and abolished in leg discs lacking aristaless activity, which was associated with strong Bar misexpression in the presumptive pretarsus. No Lim1 misexpression occurred upon aristaless misexpression. The concerted function of Lim1 and aristaless was required to maintain Fasciclin 2 expression in border cells and form a smooth pretarsus/tarsal-segment boundary. Lim1 was also required for femur, coxa and antennal development.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Inhibition of DNA topoisomerases by nidulalin A derivatives.

Three cytotoxic dihydroxanthone derivatives, nidulalin A(1), F390B(2), and F390C(3) were evaluated for inhibitory activity against DNA topoisomerases. Compounds 1 and 2 inhibited DNA topoisomerase II with IC50 values of 2.2 microM and 16 microM, and 3 inhibited DNA topoisomerase I with an IC50 value of 5.9 microM.

Enzyme Inhibitors↗
PubMed2000

Effects of adrenergic alpha2-receptor agonists on urinary bladder contraction in conscious rats.

We investigated the effects of the adrenergic alpha2-receptor agonists clonidine, oxymetazoline and tizanidine on bladder contractions induced by infusing fluid into the bladders of conscious male rats. I.v. clonidine and oxymetazoline (both 0.01 to 0.1 mg/kg) caused bladder hyperactivity, expressed by shortening of the intercontraction interval. Tizanidine (0.1 mg/kg, i.v.) caused slight shortening of the intercontraction interval. The rank order of potency was clonidine = oxymetazoline >> tizanidine. Intrathecal (i.t.) injection of 10 microg clonidine and oxymetazoline, and intracerebroventricular (i.c.v) injection at 15 microg, produced almost the same pattern of bladder hyperactivity as that observed after i.v. injection of these drugs (0.03 mg/kg, i.v.). For all three administration routes of clonidine and oxymetazoline, i.v. idazoxan (0.3 mg/kg) exerted an inhibitory effect on the bladder hyperactivity induced by these drugs, except i.c.v injection of oxymetazoline. I.t. phenylephrine (30 microg) did not change the intercontraction interval. Although i.c.v. phenylephrine (15 microg) shortened the intercontraction interval, the potency was weaker than those of i.c.v. clonidine and oxymetazoline (15 microg). These results suggest that clonidine and oxymetazoline cause bladder hyperactivity by acting at adrenergic alpha2 receptors in the micturition centers of the lumbosacral and supraspinal regions.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2000

Murine stromal cell line HESS-5 maintains reconstituting ability of Ex vivo-generated hematopoietic stem cells from human bone marrow and cytokine-mobilized peripheral blood.

Human bone marrow (BM) or mobilized peripheral blood (mPB) CD34(+) cells have been shown to loose their stem cell quality during culture period more easily than those from cord blood (CB). We previously reported that human umbilical CB stem cells could effectively be expanded in the presence of human recombinant cytokines and a newly established murine bone marrow stromal cell line HESS-5. In this study we assessed the efficacy of this xenogeneic coculture system using human BM and mPB CD34(+) cells as materials. We measured the generation of CD34(+)CD38(-) cells and colony-forming units, and assessed severe-combined immunodeficient mouse-repopulating cell (SRC) activity using cells five days after serum-free cytokine-containing culture in the presence or the absence of a direct contact with HESS-5 cells. As compared with the stroma-free culture, the xenogeneic coculture was significantly superior on expansion of CD34(+)CD38(-) cells and colony-forming cells and on maintenance of SRC activity. The PKH26 study demonstrated that cell division was promoted faster in cells cocultured with HESS-5 cells than in cells cultured without HESS-5 cells. These results indicate that HESS-5 supports rapid generation of primitive progenitor cells (PPC) and maintains reconstituting ability of newly generated stem cells during ex vivo culture irrespective of the source of samples. This xenogeneic coculture system will be useful for ex vivo manipulation such as gene transduction to promote cell division and the generation of PPC and to prevent loss of stem cell quality.

ADP-ribosyl Cyclase↗
PubMed2000

Exponential hyperbolic sine function fitting of heart rate response to constant load exercise.

We attempted to fit heart rate (HR) changes induced by constant exercise loads of different intensities to an exponential hyperbolic sine curve by the least-squares method, and we compared the results with the fitting of the changes to exponential curves. Seven healthy male volunteers performed three different intensities of constant-load exercise on a bicycle ergometer. The exponential hyperbolic sine function adequately fitted the HR responses induced by all three different intensities of loads: low (30 W: correlation coefficient, r = 0.68 +/- 0.13, mean +/- SD), moderate (75 W: r = 0.93 +/- 0.07) and high (125 W: r = 0.97 +/- 0.02). The first-order exponential curve fitted only the moderate load response. Although the second-order exponential equation fitted the HR response for both the moderate and high loads, the equation did not fit the low-load response (r = 0.43 +/- 0.26). In low-load exercise, the sum of the power of the residuals for the exponential hyperbolic sine curve fitting was significantly smaller than that for the first- or second-order exponential curve fitting. In conclusion, the exponential hyperbolic sine function is useful for quantitative analyses of the HR response to exercise loads of various intensities.

Adult↗