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Y Kawachi

Publications and source records attributed to Y Kawachi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mechanisms involved in graft-versus-host disease induced by the disparity of minor histocompatibility M1s antigens.

In this study we investigated which type of T cells: high T-cell receptor (TCRhigh, cells of thymic origin) or intermediate TCR (TCRint, cells of extrathymic origin), expanded in the liver and other organs, resulting in the induction of graft-versus-host disease (GVHD) with minor lymphocyte stimulating (M1s) disparity. When 6.5 Gy-irradiated BALB/c (H-2d M1s-1b2a) mice were injected with interleukin-2 receptor beta-chain(-) (IL-2Rbeta(-)) CD3high cells purified from the spleen of B10.D2 (H-2d M1s-1b2b) mice, IL-2Rbeta(+)CD3high cells expanded in the liver and other organs of recipient mice. The majority of these cells were found to be IL-2Ralpha(-)Mel-14(-)CD4(+)Vbeta3(+) in GVHD mice. The CDR3 region in their TCR-alphabeta (i.e. N-Dbeta-N) was polyclonal, although there were skewed usages of Vbeta3 and Jbeta2.4. The majority of cells were confirmed to be of donor origin by the individual discrimination method, namely, they originated from isolated IL-2Rbeta(-)CD3high cells. Interestingly, these T cells lacked cytotoxicity against both a natural killer (NK)-sensitive target and thymocytes with M1s disparity and nondisparity. Another important finding was that activated granulocytes expanded at generalized sites in GVHD mice. The present results raise the possibility that M1s disparity is mainly recognized by TCRhigh cells with unique properties but that direct effector cells that induce GVHD might not be such T cells but rather accompanied granulocytes.

Adoptive Transfer↗
PubMed1998

A new cytokine-dependent monoblastic cell line with t(9;11)(p22;q23) differentiates to macrophages with macrophage colony-stimulating factor (M-CSF) and to osteoclast-like cells with M-CSF and interleukin-4.

Monocytes/macrophages exert a series of important functions in vivo. To facilitate detailed investigation of their functional capacity and the mechanism leading to their differentiation, several cell lines have been established from primary material. We present here a new human monoblastic cell line, designated UG3. UG3 cells are characterized by the following features. (1) UG3 cells harbor the t(9;11)(p22;q23) translocation that results in fusion of the MLL and the AF9 genes and produce the corresponding AF9-MLL and MLL-AF9 fusion transcripts. (2) UG3 cells rely on the presence of exogenous growth factors for viability and proliferation, such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), or macrophage colony-stimulating factor (M-CSF). (3) When cultured in the presence of G-CSF, UG3 cells differentiate along the granulocytic lineage, as evidenced by segmentation of nuclei and positive staining for neutrophilic alkaline phosphatase and peroxidase. (4) When cultured in the presence of GM-CSF or M-CSF, UG3 cells differentiate into mature macrophages while preserving surface expression of CD14 and CD68 and also start to release cytokines into cell-culture supernatants. Under these culture conditions, UG3 cells also take up acetylated LDL. (5) When cultured in the presence of M-CSF and IL-4, UG3 cells differentiate into osteoclast-like multinucleated giant cells capable of bone resorption and display tartrate-resistant acid phosphatase (TRAP) activity. UG3 cells thus provide features to qualify them as a useful model to further investigate the mechanism underlying these processes and also to further elucidate the functional role of mature monocytes/macrophages or osteoclasts.

Adult↗
PubMed1998

Lazaroid U74500A is superior to U74006F in preserving rabbit heart for 24 hours.

BACKGROUND: Lazaroid, a series of 21-aminosteroids, has been shown to reduce free-radical-mediated injury after ischemia and reperfusion. Recent in vitro studies have demonstrated that, among the various compounds studied, the most efficient agent was U74500A. The question is whether these findings apply to the whole heart experiencing ischemia-reperfusion injury. In this study we compared the myocardial protective effects of U74006F, the only clinical candidate, and U74500A. METHODS: An isolated rabbit heart preparation perfused with the blood from a support rabbit was used. All hearts were divided into three groups according to the administration of U74500A (4 mg/kg, group A; n = 7), U74006F (4 mg/kg, group F; n = 7), or solvent (group S; n = 7) to the donor rabbit before preservation. After 24 hours of preservation with University of Wisconsin solution at 0 degrees C, all hearts were perfused with cross-circulated blood for 60 minutes with the Langendorff mode followed by 40 minutes in the working mode. RESULTS: After 10 minutes of reperfusion the serum lipid peroxide levels were significantly (p < 0.05) lower in group A (0.62+/-0.31 nmol/mL) than those in group S (2.1+/-1.3 nmol/mL) and group F (1.0+/-0.6 nmol/mL). The aortic flow rate at 10 mm Hg of left atrial pressure was significantly higher in group A (164+/-37 mL/min) than that of other groups (71+/-28 mL/min in group S and 97+/-28 mL/min in group F). There were no significant differences in high-energy phosphate levels after reperfusion among the three groups. CONCLUSION: These data imply that U74500A inhibits lipid peroxidation and prevents ischemia-reperfusion injury more efficiently than U74006F.

Animals↗
PubMed1998

Effects of amrinone, a phosphodiesterase inhibitor, on right ventricular/arterial coupling immediately after cardiac operations.

OBJECTIVE: Amrinone, a selective phosphodiesterase III inhibitor, is reported to have a potent inotropic effect on the left ventricle, but the effects of this drug on right ventricular contractility in the clinical setting are unknown. The concept of ventricular/arterial coupling was applied to investigate the effects of amrinone on right ventricular contractility and afterload with transesophageal echocardiography. METHODS AND RESULTS: The study was performed in the intensive care unit with 11 patients who had undergone cardiac operations. Right ventricular cross-sectional area was measured with transesophageal echocardiography equipped with a capability of automated border detection as a surrogate for right ventricular volume. Multiple pressure-area loops were obtained by reducing preload to measure end-systolic elastance and effective arterial elastance. External work and pressure-volume area were also measured to calculate the efficiency of energy transfer from pressure-volume area to external work. Nitroprusside (0.3 to 0.5 microg x kg(-1) x min(-1)) and amrinone (1 mg x kg(-1) intravenously followed by 10 microg x kg(-1) x min(-1)) were administered. With nitroprusside infusion, end-systolic elastance and effective arterial elastance remained unchanged (end-systolic elastance, 4.73 +/- 2.18 mm Hg/cm2 to 4.65 +/- 2.09 mm Hg/cm2; effective arterial elastance, 8.05 +/- 3.84 mm Hg/cm2 to 7.70 +/- 3.64 mm Hg/cm2). In contrast, amrinone reduced afterload (effective arterial elastance, 8.82 +/- 3.99 mm Hg/cm2 to 7.05 +/- 4.01 mm Hg/cm2, p = 0.004) and enhanced contractility (end-systolic elastance, 4.47 +/- 1.79 mm Hg/cm2 to 6.56 +/- 2.22 mm Hg/cm2, p = 0.007). Consequently, amrinone decreased the ventricular/arterial coupling ratio (effective arterial elastance/end-systolic elastance, 2.40 +/- 1.45 to 1.16 +/- 0.63, p = 0.009) and improved the efficiency of energy transfer (external work/pressure-volume area, 0.44 +/- 0.15 to 0.54 +/- 0.15, p = 0.013). CONCLUSIONS: Right ventricular pressure-area relations obtained with transesophageal echocardiography could successfully separate the simultaneous change in right ventricular systolic mechanics and afterload caused by amrinone. Amrinone caused enhancement of right ventricular contractility and afterload reduction.

Adult↗
PubMed1998

14q11 abnormality and trisomy 8q are not common in Japanese T-cell prolymphocytic leukemia.

We studied ten cases of Japanese T-cell prolymphocytic leukemia (T-PLL) collected over the last 9 years. Median age was 61 years with a male predominance (M:F, 8:2). The main disease features were splenomegaly, lymphadenopathy, hepatomegaly, skin lesions and serous effusions. The clinical course was progressive with a median survival of 10 months. Immunophenotyping showed that the prolymphocytes had a post-thymic phenotype (TdT-, CD1a-, CD2+, CD3+, CD5+, CD7+) with a predominant CD4+ immunophenotype. Cytogenetic analysis showed no consistent abnormalities. 14q abnormality and trisomy 8q, which are frequently seen in T-PLL of Western countries, were found in only two and zero cases, respectively. We conclude that the clinical and biological characteristics of T-PLL in Japan are almost the same as those in Western countries. However, the cytogenetic findings of T-PLL in Japan might be different.

Adult↗
PubMed1998

Arresting donor hearts with extracellular-type cardioplegia prevents vasoconstriction induced by UW solution.

The effects of arresting donor hearts with University of Wisconsin solution was investigated. Donor dogs were divided into two groups according to the technique used for arresting the heart. In group I (n = 6) the heart was arrested with University of Wisconsin solution, whereas in group II (n = 6) extracellular-type cardioplegia (K+ = 20 mmol/liter) was used to induce cardioplegic arrest. Aortic root pressure was measured during the infusion of solution at constant flow. In both groups, the hearts were then flushed and stored in cold University of Wisconsin solution for 6 h. The hearts were transplanted orthotopically and disconnected from cardiopulmonary bypass. Left ventricular function was evaluated by pressure-volume relations using a conductance catheter. Peak aortic root pressure during the infusion was significantly higher in group I than in group II, although post-transplant left ventricular function was similar in both groups. Although there was no difference in cardiac function after implantation, donor hearts should be arrested by extracellular-type cardioplegia to prevent coronary vasoconstriction associated with preservation in University of Wisconsin solution.

Adenosine↗
PubMed1998

A novel donor splice site mutation in the C1 inhibitor gene of a patient with type I hereditary angioneurotic edema.

We studied the molecular genetic basis of a C1 inhibitor deficiency in a patient with type I hereditary angioneurotic edema using both the polymerase chain reaction and nucleotide sequencing. A single nucleotide change (T-->A) at the GT 5' donor splice recognition motif in the seventh intron of the C1 inhibitor gene was detected. A restriction site analysis of the C1 inhibitor gene in the patient's family indicated that this mutation is correlated with a decreased level of C1 inhibitor activity. A northern blot analysis demonstrated C1 inhibitor mRNA to have a normal size, but its contents were reduced by about 50% compared with a normal subject. As the donor splice site is essential for an excising of the intron during mRNA processing, aberrant mRNA splicing may cause a rapid degradation of the transcript, thus resulting in the onset of hereditary angioneurotic edema.

Adult↗
PubMed1998

Angiokeratoma corporis diffusum associated with galactosialidosis.

We describe a 34-year-old Japanese man with generalized angiokeratomas and various neurological symptoms since childhood. A number of reddish papules were scattered over his entire body and were especially numerous on his elbows, knees, penis and scrotum. An electron-microscopic study revealed a number of vacuoles in the cytoplasm of the vascular endothelial cells. This finding suggests that the angiokeratomas resulted from an injury of the endothelial cells due to the storage of metabolic material. A laboratory examination demonstrated a deficiency of both the beta-galactosidase and neuramidase activity in his leukocytes and fibroblasts. A restriction site analysis of PCR-amplified genomic DNA revealed that the patient had an mRNA splicing junction mutation at the 5' donor splice site of the exon 7/intron 7 junction in the protective protein gene.

Adult↗
PubMed1998

[Fatal pulmonary thromboembolism in a patient with paroxysmal nocturnal hemoglobinuria].

A 38 year old woman with paroxysmal nocturnal hemoglobinuria was admitted to our hospital because of hemoptysis. Pulmonary infarction was diagnosed by the perfusion lung scan. In spite of the administration of prednisolone, dextran, low molecular weight heparin, and warfarin, she died of pulmonary infarction and secondary pulmonary hypertension. Autopsy revealed thromboembolism of both pulmonary arteries and hepatic central vein thrombosis. Recent understanding of the pathogenesis and incidence of thromboembolism in paroxysmal nocturnal hemoglobinuria was discussed.

Adult↗
PubMed1998

[The frequency and development of tissue iron deficiency in 6 iron deficiency anemia patients with plummer-vinson syndrome].

The physical signs of tissue iron deficiency include smooth and red tongue, angular stomatitis, koilonychia, and pica. The incidence of these conditions is unknown in Japan. We evaluated the frequency and development of tissue iron deficiency in 353 patients with iron deficiency anemia. The frequency of tissue iron deficiency was 6.8%; papillary atrophy of the tongue, 5.4%; abnormal nails, 5.4%; angular stomatitis, 1.1%; Plummer-Vinson syndrome, 1.7%; and pica, 0.06%. These findings were compared with the date collected by Wintrobe and Beveridge. The development and incidence of tissue iron deficiency correlated significantly with the severity of iron deficiency anemia.

Adult↗
PubMed1997

Synergistic immunosuppression caused by high-dose methylprednisolone and cardiopulmonary bypass.

BACKGROUND: Steroid use during cardiac operations may reduce the risk of postperfusion lung syndrome, but both cardiopulmonary bypass and steroids are immunosuppressive. The synergistic effects of the bypass and steroids on patients' immunologic activities, hemodynamics, and metabolisms during and after heart operations have not been clarified systematically. METHODS: Twenty-four patients undergoing valve replacement were studied in a randomized, double-blind trial. Twelve of these patients (S group) received bolus methylprednisolone, 20 mg/kg body weight, and the remaining 12 patients (C group) received a placebo intravenously before and after bypass. Blood cell count, C-reactive protein, lymphocyte surface markers (CD3, CD4, CD8, CD16, and CD20), phytohemagglutinin response, interleukin-2 production, and natural killer cell activity were examined on admission through day 7. Cardiac output, blood gas, electrolyte, lactate, and serum glucose levels were examined perioperatively. RESULTS: The peak white blood cell count in the S group was higher than that in the C group (analysis of variance: p [group] = 0.0436). The peak C-reactive protein level was higher in the C group than in the S group (p [group] < 0.0001). From the analysis of the surface markers, the steroid increased the natural killer cells before and soon after bypass (p [group] = 0.0117), and later tended to increase the CD4+ T and B cells during the postoperative recovery period. The phytohemagglutinin response in both groups decreased after bypass (p [time] < 0.0001), but the steroid caused exaggerated decreases before (p < 0.01 by Student's t test) and soon after (p < 0.001) bypass in the S group (analysis of variance: p [group] = 0.0127). The interleukin-2 production was suppressed by bypass alone after the bypass in the C group, but was further suppressed by the steroid before and after bypass in the S group (p [group] = 0.0446). The cardiac index, water balance, electrolytes, arterial oxygen tension, and timing of extubation were not different between the groups. In contrast, the glucose (p [group] = 0.0486) and lactate (p [group] = 0.0525) levels were higher in the S group than those in the C group. CONCLUSIONS: T-cell functions are synergistically suppressed by cardiopulmonary bypass and high-dose methylprednisolone in heart operations. The hemodynamic benefits of the steroid are negligible, whereas glucose tolerance is worsened by the steroid during bypass.

Antigens, Surface↗
PubMed1997

Interleukin-1 and lipopolysaccharide enhance intercellular adhesion molecule-1 expression in cell lines of human squamous cell carcinoma.

We show that in two cell lines of human squamous cell carcinoma (SCC) which slightly express intercellular adhesion molecule-1 (ICAM-1), the expression is enhanced not only by interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) but also by interleukin-1 (IL-1) and lipopolysaccharide (LPS). This expression is totally dependent on the increase of ICAM-1 mRNA. This evidence contrasts with previously reported findings indicating that, in human cultured keratinocytes, ICAM-1 expression is induced by IFN-gamma and TNF-alpha, and not by either IL-1 or LPS. This result suggests that various cytokines or agents easily enhance ICAM-1 expression in SCC cell lines, and may explain the clinical finding that ICAM-1 expression increases according to the progression of malignant tumors.

Actins↗
PubMed1997

Eosinophil-colony stimulating activity in blister fluid of bullous pemphigoid.

We examined eosinophil-colony stimulating activity in blister fluid or serum obtained from patients with bullous pemphigoid using the methylcellulose semi-solid hematopoietic stem cell culture system, and demonstrated that the blister fluid of patients with bullous pemphigoid generated strong eosinophil-colony stimulating activity. This evidence suggests that eosinophil-colony stimulating activity in blister fluid probably influences the induction of eosinophilia in bullous pemphigoid.

Aged↗
PubMed1997

Mechanism of abrupt hypotension with stretch of right atrium during cardiac surgery.

During cardiac surgery abrupt hypotension sometimes occurs by the atrium being pulled, though the hypotensive mechanism is not known. The effects of mechanical stretching of the right atrium on haemodynamics and renal sympathetic nerve activity in the anesthetized rabbit was investigated. During stretching of the right atrial appendage with a metal weight (right atrial stretch), both mean arterial pressure (mAP) and renal sympathetic nerve activity significantly decreased. Bilateral vagotomy significantly reduced the change in mean arterial pressure with right atrial stretch (P < 0.01), and significantly increased renal sympathetic nerve activity (P < 0.01). The duration of the decreases of mean arterial pressure with right atrial stretch was significantly shortened after vagotomy. Decreases of blood flow of the descending aorta with right atrial stretch were observed and not affected by vagotomy. These results suggest that hypotension with mechanical stimulation of the right atrium is not only due to the decrease in cardiac output but also to sympathetic inhibition through the vagus via cardiac baroreflex.

Animals↗
PubMed1997

Self-reactive forbidden clones are confined to pathways of intermediate T-cell receptor cell differentiation even under immunosuppressive conditions.

It is believed that self-reactive forbidden T-cell clones are generated by 'failure' of the pathway of T-cell differentiation in the thymus, if it is disturbed. We examined how such forbidden clones are generated under immunosuppressive conditions. Mice were treated with an injection of deoxyspergualin, FK506, or cycloporin A. From day 3, the number of cells yielded by various organs decreased. Because of the resistance of intermediate (int) T-cell receptor (TCR) cells (i.e. TCRint cells), they became more prominent in proportion than TCRhigh cells. TCRhigh cells are conventional T cells generated through the mainstream in the thymus, whereas TCRint cells are primordial T cells generated by the extrathymic pathway or an alternative intrathymic pathway. Similar to untreated mice, forbidden V beta 3+ and V beta 11+ clones in C3H/He (Mls-1b2a) mice were confined to TCRint cells after treatment; there was no leakage of forbidden clones into TCRhigh cells in the thymus and periphery. In parallel with the increase in the proportion of TCRint cells, the proportion of forbidden clones also increased under immunosuppressive states, especially in the liver. Liver mononuclear cells isolated from treated mice still had the potential to mediate autologous killing. The present results suggest that the generation of self-reactive clones is highly restricted to the pathways of TCRint cell differentiation even under immunosuppressive conditions.

Animals↗