Search PubMed⌕ Search

Biomedical subjects

T Wakatsuki

Publications and source records attributed to T Wakatsuki.

At least 19 recordsLinked to original sources
PubMed2000

Identification and characterization of differentially expressed mRNAs in HIV type 1-infected human T cells.

We used a novel differential display (DD) technique to identify host factors involved in virus replication, pathogenesis, and host response in HIV-1-infected T cells. Thirteen cDNA fragments differentially expressed in HIV-1NL4-3-infected MT-4 cells prior to the occurrence of specific apoptotic cell death were sequenced and identified. Two of seven elevated genes were identical to HIV-1 sequences and the other five were MIP-1alpha, ACTE-III, CD11c, arginase I, and CCR5. The six downregulated genes included prothymosin-a, Jaw-1, proteasome subunit XAPC7, splicing factor 9G8, GA17 protein, and an unknown mRNA. Northern blot and RT-PCR analyses confirmed the altered gene expressions in MT-4 cells as well as in another T cell line, MOLT-4. We also revealed that the amount of MIP-1alpha in culture supernatant of HIV-1-infected cells was increased by more than 15-fold relative to control cells, and the expression of its receptor CCR5 was cooperatively upregulated on the surface of these cells. Furthermore, the upregulation of CD11c after HIV-1 infection was slightly inhibited by blocking the MIP-1alpha-mediated signal transduction. These results indicate that genes altered on HIV-1 infection may be mutually organized and play an important role in HIV-1-induced pathogenesis.

CD4-Positive T-Lymphocytes↗
PubMed2000

Detection of left ventricular regional relaxation abnormalities and asynchrony in patients with hypertrophic cardiomyopathy with the use of tissue Doppler imaging.

BACKGROUND: It is well known that the distribution and magnitude of left ventricular (LV) hypertrophy are not uniform in patients with hypertrophic cardiomyopathy (HCM), which results in regional heterogeneity of LV early diastolic function. The advent of tissue Doppler imaging (TDI) has allowed the noninvasive evaluation of regional LV wall motion velocities. The aim of this study was to evaluate regional LV relaxation abnormalities and asynchrony noninvasively in patients with HCM by using pulsed and color-coded TDI. METHODS AND RESULTS: We studied 20 patients with asymmetric septal hypertrophy (HCM group) and 18 age-matched normal patients (control group). The peak early diastolic motion velocity (Ew) and time from the aortic component of the second heart sound to the peak of the Ew (II(A)-Ew) were measured by pulsed TDI. The myocardial velocity gradient during early diastole (MVG-Ew) also was measured by color-coded TDI. Mean values for these parameters were determined on the basis of measurements made at 2 sites of the ventricular septum or posterior wall at the levels of chordae tendineae and papillary muscles. The mean Ew and mean MVG-Ew for the ventricular septum and posterior wall were significantly lower, and mean II(A)-Ew was significantly prolonged in the HCM group compared with the control group. This difference was most pronounced in the hypertrophied ventricular septum of the HCM group. The standard deviations of II(A)-Ew for the ventricular septum and posterior wall were significantly greater in the HCM group than in the control group. The time constant of LV pressure decay during isovolumic diastole (tau) correlated inversely with Ew and MVG-Ew and correlated directly with II(A)-Ew. Furthermore, tau correlated directly with the standard deviation of the II(A)-Ew. CONCLUSIONS: LV early diastolic function in patients with HCM may be mediated by an augmentation of regional LV relaxation abnormalities and asynchrony.

Adult↗
PubMed2000

Cell mechanics studied by a reconstituted model tissue.

Tissue models reconstituted from cells and extracellular matrix (ECM) simulate natural tissues. Cytoskeletal and matrix proteins govern the force exerted by a tissue and its stiffness. Cells regulate cytoskeletal structure and remodel ECM to produce mechanical changes during tissue development and wound healing. Characterization and control of mechanical properties of reconstituted tissues are essential for tissue engineering applications. We have quantitatively characterized mechanical properties of connective tissue models, fibroblast-populated matrices (FPMs), via uniaxial stretch measurements. FPMs resemble natural tissues in their exponential dependence of stress on strain and linear dependence of stiffness on force at a given strain. Activating cellular contractile forces by calf serum and disrupting F-actin by cytochalasin D yield "active" and "passive" components, which respectively emphasize cellular and matrix mechanical contributions. The strain-dependent stress and elastic modulus of the active component were independent of cell density above a threshold density. The same quantities for the passive component increased with cell number due to compression and reorganization of the matrix by the cells.

Animals↗
PubMed2000

A cell-based constitutive relation for bio-artificial tissues.

By using a combination of continuum and statistical mechanics we derive an integral constitutive relation for bio-artificial tissue models consisting of a monodisperse population of cells in a uniform collagenous matrix. This constitutive relation quantitatively models the dependence of tissue stress on deformation history, and makes explicit the separate contribution of cells and matrix to the mechanical behavior of the composite tissue. Thus microscopic cell mechanical properties can be deduced via this theory from measurements of macroscopic tissue properties. A central feature of the constitutive relation is the appearance of "anisotropy tensors" that embody the effects of cell orientation on tissue mechanics. The theory assumes that the tissues are stable over the observation time, and does not in its present form allow for cell migration, reorientation, or internal remodeling. We have compared the predictions of the theory to uniaxial relaxation tests on fibroblast-populated collagen matrices (FPMs) and find that the experimental results generally support the theory and yield values of fibroblast contractile force and stiffness roughly an order of magnitude smaller than, and viscosity comparable to, the corresponding properties of active skeletal muscle. The method used here to derive the tissue constitutive equation permits more sophisticated cell models to be used in developing more accurate representations of tissue properties.

Animals↗
PubMed2000

Coronary flow velocity immediately after primary coronary stenting as a predictor of ventricular wall motion recovery in acute myocardial infarction.

OBJECTIVES: The purpose of this study was to examine the relationship between the pattern of coronary blood flow velocity immediately after successful primary stenting and the recovery of left ventricular (LV) wall motion in patients with acute myocardial infarction (AMI). BACKGROUND: It is difficult to predict the recovery of LV wall motion immediately after direct angioplasty in AMI. Recent reports indicate that dysfunctional coronary microcirculation is an important determinant of prognosis for AMI patients after successful reperfusion. METHODS: We measured left anterior descending coronary flow velocity variables using a Doppler guide wire immediately after successful primary stenting in 31 patients with their first anterior AMI. The patients were divided into two groups: those with and those without early systolic reverse flow (ESRF). Changes in LV regional wall motion (RWM) and ejection fraction (EF) at admission and at discharge were compared between the two groups. Coronary flow velocity variables immediately after primary stenting were compared with changes in left ventriculographic indexes. RESULTS: The change in RWM was significantly greater in the non-ESRF group than it was in the ESRF group (0.9 +/- 0.7 vs. -0.1 +/- 0.3 standard deviation/chord, respectively, p < 0.001). The change in EF was also significantly greater in the non-ESRF group than it was in the ESRF group (10 +/- 10 vs. 1 +/- 6%, respectively, p < 0.05). In the non-ESRF group (diastolic to systolic velocity ratio [DSVR] <3.0), the DSVR correlated positively with the change in RWM (r = 0.60, p < 0.005, n = 24) and the change in EF (r = 0.52, p < 0.01). CONCLUSIONS: The coronary flow velocity pattern measured immediately after successful primary stenting is predictive of the recovery of regional and global LV function in patients with AMI.

Aged↗
PubMed2000

Circulating adhesion molecules and severity of coronary atherosclerosis.

BACKGROUND: Circulating leukocytes are recruited at atherosclerotic sites through a family of adhesion molecules. Circulating forms of adhesion molecules in peripheral blood can be quantified now. OBJECTIVE: To evaluate the relationship between circulating adhesion molecules and severity of coronary atherosclerosis. METHODS: Subjects included 81 patients undergoing diagnostic coronary angiography, 12 of whom had normal coronary arteries (control group). The remaining 69 patients with demonstrable coronary atherosclerosis were divided into two groups by use of Gensini scores, namely mild atherosclerosis (n = 36, Gensini score 1-20) and severe atherosclerosis (n = 33, Gensini score > 20). Serum levels of circulating intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin of groups measured before angiography were compared. RESULTS: Circulating levels of ICAM-1 in members of mild and severe atherosclerosis groups were significantly higher than those in members of the control group, whereas there was no significant difference among circulating levels of VCAM-1 in members of the three groups. Circulating levels of E-selectin in members of the mild atherosclerosis group were significantly higher than those in members of the severe atherosclerosis and control groups. CONCLUSIONS: These findings suggest that E-selectin is related to the early stage, and ICAM-1 is related to the advanced stage, of coronary atherosclerosis. With progression of atherosclerosis, one-step adhesion by ICAM-1 could become more important than multistep adhesion involving E-selectin, ICAM-1, and VCAM-1. These molecules may serve as markers for severity of coronary atherosclerosis.

Adult↗
PubMed2000

Leukocyte counts and concentrations of soluble adhesion molecules as predictors of coronary atherosclerosis.

BACKGROUND: Authors of recent studies have reported that there is a relationship between level of adhesion molecules and atherosclerosis. In an animal study it was demonstrated that there is an interaction between adhesion molecules and leukocytes in atherosclerotic tissue. OBJECTIVE: To study the relationships between coronary-artery atherosclerosis and both differential blood-leukocyte count and concentrations of soluble adhesion molecules in patients with and without coronary artery disease (CAD). METHODS: Our subjects were 168 patients who underwent diagnostic coronary angiography. Forty-eight patients had normal coronary angiograms (control group), and 120 patients had significant coronary-artery stenoses (diameter stenosis > 70%) in at least one major coronary-artery branch (CAD group). Total and differential blood-leukocyte counts, and concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were assayed prior to angiography. RESULTS: Monocyte counts for patients in the CAD group were significantly greater than those for patients in the control group (366 +/- 99 versus 258 +/- 44/microl, P < 0.0001), as were the sICAM-1 concentrations (272 +/- 52 versus 203 +/- 24 ng/ml, P < 0.0001). The mean concentrations of sVCAM-1 in members of the two groups were the same (671 +/- 138 versus 668 +/- 97 ng/ml, P=0.4). There was a higher incidence of significant coronary-artery stenosis among patients with both a high monocyte count and a high concentration of sICAM-1 (> or = mean + SD) than there was among patients with a low monocyte count and a low concentration of sICAM-1 (> or = mean - SD; 100 versus 25%, P < 0.0001). CONCLUSIONS: Higher levels both of monocyte counts and of serum concentrations of ICAM-1 may serve as markers for coronary atherosclerosis.

Biomarkers↗
PubMed2000

Patient with atrioventricular node reentrant tachycardia with eccentric retrograde left-sided activation: treatment with radiofrequency catheter ablation.

We describe a patient with supraventricular tachycardia with triple atrioventricular (AV) node pathway physiology. A discontinuous curve was present in the antegrade AV nodal function curves. During right ventricular pacing, the earliest retrograde atrial activation was recorded at the left-sided coronary sinus electrode. The retrograde ventricular-atrial interval was long and had decremental conduction. We induced a slow-slow AV node reentrant tachycardia (AVNRT) with eccentric retrograde left-sided activation. After slow pathway ablation, dual AV nodal pathway physiology was present. AVNRT with eccentric retrograde left-sided activation is relatively rare, and our findings suggest that eccentric retrograde left-sided atrial inputs consist partially of a slow pathway and disappear with slow pathway ablation.

Atrial Function, Left↗
PubMed2000

Sjögren's syndrome with primary biliary cirrhosis, complicated by transverse myelitis and malignant lymphoma.

A 53-year-old woman with Sjögren's syndrome (SS) and primary biliary cirrhosis (PBC) complicated by transverse myelitis (TM) and malignant lymphoma (ML) is reported. TM has been described only in seven cases of primary SS, including three with PBC and four without PBC. The features of SS associated with PBC and complicated by TM were less typical compared with those seen in SS without PBC complicated by TM. This case is the first report of a case with SS, PBC, TM and ML. SS in association with PBC is, in general, overlooked, but such cases must be investigated with great caution for extraglandular complications.

Abdomen↗
PubMed2000

Hepatopulmonary syndrome-discussion of cardiopulmonary parameters.

We report a 70-year-old man with hepatopulmonary syndrome (HPS) in C liver cirrhosis. Hypoxemia worsened markedly, especially on exertion, while the hepatic function was clinically stable. Contrast echocardiography, 99mTc macroaggregated albumin (99mTcMAA) lung scan, and pulmonary angiography were performed. The findings suggested the presence of both intrapulmonary vascular dilatation and substantial right-to-left shunt. The contribution of intrapulmonary vascular abnormalities in patients with severe liver cirrhosis without abnormal chest radiography and spirometry tests when marked hypoxemia is present should be investigated.

Aged↗
PubMed1999

Serial analysis of gene expression in HIV-1-infected T cell lines.

The gene expression profile of the HIV-1 infection state was analyzed in the human T cell line MOLT-4. Using the serial analysis of gene expression (SAGE) method, a total of 142¿ omitted¿603 SAGE tags were sequenced and identified, representing 43¿ omitted¿581 unique mRNA species. Comparison of expression patterns revealed that 53 cellular genes were differentially expressed upon HIV-1 infection. Northern blot and RT-PCR analyses confirmed the altered expression of the genes in both MOLT-4 and MT-4 cells. Up-regulated genes were mainly composed of transcription factors and genes related to T cell activation, whereas down-regulated genes were comprised of mitochondrial proteins, actin-related factors and translational factors. These findings indicate that persistent T cell activation, which may accelerate HIV-1 replication, and the disruption of cellular housekeeping genes including those involved in anti-apoptotic systems, may play an important role in HIV-1-induced pathogenesis.

Apoptosis↗
PubMed1999

Identification and characterization of genes associated with human hepatocellular carcinogenesis.

Eight cDNAs encoding galectin 4 (Gal-4), UGT2B4 (UDP-glucuronosyltransferase), ribosomal phosphoprotein P0 (rpP0), dek, insulin-like growth factor binding protein (IGFBP) 1, vitronectin, retinoic acid-induced gene E (RIG-E), and CYP3A4 (cytochrome P450 nifedipine oxidase) were identified as differentially expressed genes between human hepatocellular carcinoma (HCC) and matched nontumorous liver tissues. Higher levels of UGT2B4, rpP0, dek, vitronectin, Gal-4, and IGFBP-1 mRNAs combined with a lower level of RIG-E mRNA were observed in at least four of five primary HCCs compared to matched nontumorous liver tissues. Furthermore, a pathological study suggested that the levels of UGT2B4, rpP0, dek, and vitronectin increased and the level of RIG-E decreased with the histological grading. On the other hand, the expression of CYP3A4 mRNA and CYP3A7 (P-450 Fla) mRNA, a transcript found in the fetus and highly homologous to CYP3A4, was higher in all nontumorous liver and some of the carcinoma tissues from five HCC patients, whereas it was significantly lower in normal liver tissues from two non-HCC patients. The examination using HCC cell lines HuH-7 and HepG2 under different growth conditions suggested that the expression of dek mRNA was growth-associated. In contrast, the expression of Gal-4, UGT2B4, IGFBP-1, and RIG-E mRNAs was regulated in a cell density-dependent manner: the levels of Gal-4, UGT2B4, and IGFBP-1 were undetectably low, whereas the level of RIG-E was high in rapidly proliferating, subconfluent HCC cells in 10% serum; however, the expression levels were reversed in dense, overcrowded cultures. In addition, IGFBP-1 and Gal-4 mRNAs were also induced by reducing the serum concentration to 0.1%. We also demonstrated that sodium butyrate, an inducer of differentiation, up-regulated and down-regulated RIG-E and dek mRNAs, respectively, in a dose-dependent manner in HuH-7 cells, supporting, in part, our pathological observation. In summary, therefore, high expression of Gal-4, UGT2B4, rpP0, dek, IGFBP-1, and vitronectin, together with low expression of RIG-E, was correlated with the malignant potential of HCC. CYP3A4 and CYP3A7 could be induced in HCC-bearing livers. These transcripts are differentially regulated depending on cell-cell contact, serum growth factors, growth and differentiation status, and/or other mechanisms in premalignant and malignant liver cells.

Antigens, Surface↗
PubMed1999

Serial analysis of gene expression in a microglial cell line.

We used the serial analysis of gene expression (SAGE) method to systematically analyze transcripts present in a microglial cell line. Over 10,000 SAGE tags were sequenced, and shown to represent 6,013 unique transcripts. Among the diverse transcripts that had not been previously detected in microglia were those for cytokines such as endothelial monocyte-activating polypeptide I (EMAP I), and for cell surface antigens, including adhesion molecules such as CD9, CD53, CD107a, CD147, CD162 and mast cell high affinity IgE receptor. In addition, we detected transcripts that were characteristic of hematopoietic cells or mesodermal structures, such as E3 protein, A1, EN-7, B94, and ufo. Furthermore, the profile contained a transcript, Hn1, that is important in hematopoietic cells and neurological development (Tang et al. Mamm Genome 8:695-696, 1997), suggesting the probable neural differentiation of microglia from the hematopoietic system in development. Messenger RNA expression of these genes was confirmed by RT-PCR in primary cultures of microglia. Significantly, this is the first systematic profiling of the genes expressed in a microglial cell line. The identification and further characterization of the genes described here should provide potential new targets for the study of microglial biology.

Animals↗
PubMed1999

Collagen receptor control of epithelial morphogenesis and cell cycle progression.

To define the unique contributions of the alpha subunit cytoplasmic tails of the alpha(1)beta(1) and alpha(2)beta(1) integrin to epithelial differentiation and branching morphogenesis, a variant NMuMG cell line lacking alpha(1)beta(1) and alpha(2)beta(1) integrin expression was stably transfected with the full-length alpha(2) integrin subunit cDNA (X2C2), chimeric cDNA consisting of the extracellular and transmembrane domains of the alpha(2) subunit and the cytoplasmic domain of the alpha(1) subunit (X2C1), or alpha(2) cDNA truncated after the GFFKR sequence (X2C0). The X2C2 and X2C1 transfectants effectively adhered, spread, and formed focal adhesion complexes on type I collagen matrices. The X2C0 transfectants were less adherent to low concentrations of type I collagen, spread less well, and formed poorly defined focal adhesion complexes in comparison to the X2C2 and X2C1 transfectants. The X2C2 and X2C1 transfectants but not the X2C0 transfectants proliferated on collagen substrates. Only the X2C2 transfectants developed elongate branches and tubules in three-dimensional collagen gels and migrated on type I collagen. These findings suggest a unique role for the alpha(2) integrin cytoplasmic domain in postligand binding events and cooperative interactions with growth factors that mediate epithelial differentiation and branching morphogenesis. Either intact alpha(1) or alpha(2) integrin subunit cytoplasmic domain can promote cell cycle progression.

Animals↗
PubMed1999

Effect of aging on diastolic left ventricular myocardial velocities measured by pulsed tissue Doppler imaging in healthy subjects.

We evaluated the effect of aging on diastolic left ventricular (LV) wall motion velocity in 80 healthy persons with the use of pulsed tissue Doppler imaging. The wall motion velocity patterns were recorded at the middle regions of the LV posterior wall and ventricular septum in the parasternal (along the short axis) and apical (along the long axis) LV long-axis views. In the posterior wall, the peak early diastolic wall motion velocities (Ews) along both axes correlated inversely with age (long axis: r = -0.61, P <. 0001; short axis: r = -0.55, P <.0001), and the peak atrial systolic wall motion velocities(Aws) along both axes correlated directly with age (long axis: r = 0.59, P <.0001; short axis: r = 0.65, P <.0001). In the ventricular septum, the Ew along the long axis correlated inversely with age (r = -0.51, P <.0001), and the Aws along both axes correlated directly with age (long axis: r = 0.57, P <.0001; short axis: r = 0.53, P <.0001). The Ews along both axes at the posterior wall correlated directly with the peak early diastolic transmitral flow velocity. The Aws along both axes at the ventricular septum and posterior wall correlated directly with the peak atrial systolic transmitral flow velocity. The times from the second heart sound to the peak of the early diastolic waves of the ventricular septum and posterior wall along both axes significantly increased with age. The times from the aortic component of the second heart sound to the peak of the early diastolic motion velocities along both axes were significantly longer at the ventricular septum than at the posterior wall. Pulsed tissue Doppler imaging may be useful for evaluating the effect of aging on diastolic LV function in healthy persons.

Aging↗
PubMed1999

Pulsed tissue Doppler imaging of left ventricular systolic and diastolic wall motion velocities to evaluate differences between long and short axes in healthy subjects.

Our objective was to evaluate in healthy subjects the left ventricular (LV) wall motion velocities along the long and short axes by means of pulsed tissue Doppler imaging (TDI) to clarify the differences in the LV systolic and diastolic function between both axes. Wall motion velocities were recorded at the mid-wall portion of the middle site of the LV posterior wall in the parasternal long-axis view, and at the subendocardial portion of the middle site of the LV posterior wall in the apical long-axis view by pulsed TDI in 35 healthy subjects (mean age 26 +/- 10 years, mean heart rate 72 +/- 7 bpm). In all subjects, the LV pressure curve, its first derivative (dP/dt), the LV wall motion velocity, the phonocardiogram, and the electrocardiogram were simultaneously recorded. The systolic wave of the LV posterior wall motion velocity exhibited 2 peaks: the first and second systolic waves (Swl and Sw2, respectively). The diastolic wave also exhibited 2 peaks, the early diastolic and atrial systolic waves. The Swl along the long axis was greater than either the Sw1 and Sw2 along the short axis or the Sw2 along the long axis. The peak Sw1 along the long axis coincided with the peak dP/dt and was slightly earlier than the peak Swl along the short axis. The onset of Sw1 along the long axis coincided with the onset of the first heart sound. The Sw2 along the short axis was greater than that along the long axis. The early diastolic wave along the short axis was greater than that along the long axis, whereas the atrial systolic wave along the long axis was greater than that along the short axis. Thus, in healthy subjects, shortening of the longitudinal fibers predominated over that of the circumferential fibers during early systole, whereas shortening of the circumferential fibers predominated over the longitudinal fibers during the ejection phase. During diastole, the circumferential fibers predominated in the LV wall expansion at early diastole, whereas the longitudinal fibers predominated at atrial systole. In conclusion, pulsed TDI provided information that is useful in understanding the characteristics of LV wall motion along the long and short axes.

Adult↗