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Biomedical subjects

M Adachi

Publications and source records attributed to M Adachi.

At least 271 records · Page 15Linked to original sources
PubMed1997

Interleukin-2 induces tyrosine phosphorylation of SHP-2 through IL-2 receptor beta chain.

Coupling of interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) induces rapid increase in tyrosine phosphorylation of cellular substrates through activation of non-receptor protein tyrosine kinases. Here, we report that stimulation through the IL-2R induced tyrosine phosphorylation of the SH2-containing protein-tyrosine phosphatase SHP-2 in F7, a hematopoietic BAF-B03 transfectant clone expressing the IL-2Rbeta chain. The tyrosine phosphorylation of SHP-2 was specific since another protein-tyrosine phosphatase SHP-1, which is structurally homologous to SHP-2, was not tyrosine phosphorylated. The IL-2-induced tyrosine phosphorylation of SHP-2 required the acidic region within the IL-2Rbeta chain where Src-family PTKs interact. Though the serine-rich region within IL-2Rbeta chain was also required for the phosphorylation of SHP-2, Jak3 activation was dispensable. In COS-7 cells, co-expression of SHP-2 with Lyn resulted in increased tyrosine phosphorylation levels of SHP-2, whereas co-expression of SHP-2 with Fyn failed to alter the levels significantly. Considering that Lyn and Fyn are major Src-family PTKs expressed in BAF-B03 cells, our data suggest that Lyn may be principally responsible for the tyrosine phosphorylation of SHP-2 in F7 cells. Furthermore, the IL-2 stimulation also induced tyrosine phosphorylation of SHP-2 in the human IL-2-dependent T-cell line ILT-Mat. Taken together, these studies demonstrate an involvement of SHP-2 in the IL-2-mediated signaling events through the activation of specific PTKs.

Animals↗
PubMed1997

Pluripotent hemopoietic stem cells are c-kit<low.

Pluripotent hemopoietic stem cells (P-HSCs) were thought to be c-kit+, but recent reports indicate that they are c-kit(low). In the present report, we provide evidence using Ly5 congenic mice that P-HSCs are c-kit(<low). Lineage-negative (Lin-)/CD71- cells among bone marrow cells (BMCs) from C57BL/6 Ly5.1 mice were separated into major histocompatibility complex class I(high) (class I(high))/c-kit(low) and class I(high)/ c-kit(<low) populations. Each population (500 cells) was transplanted into lethally (9.0 Gy) irradiated C57BL/6 Ly5.2 congenic mice along with Ly5.2 (2 x 10(5)) compromised cells. Donor-derived Ly5.1+ cells were detected 6 months after transplantation in primary recipients reconstituted with either class I(high)/c-kit(low) or class I(high)/c-kit(<low) cells. BMCs (1 x 10(6)) from the primary recipients were further transplanted into secondary recipients (Ly5.2 mice) to assess their long term repopulating activity. Six months after bone marrow transplantation, Ly5.1+ cells in all lineages were detected only in secondary recipients that had been given BMCs from the primary recipients reconstituted with class I(high)/c-kit(<low) cells but not in cells that were class I(high)/c-kit(low). When the BMCs (1 x 10(6)) of these secondary recipients were further transplanted into tertiary recipients, all tertiary recipients that had been given BMCs from the secondary recipients originally reconstituted with Lin-/CD71-/class I(high)/c-kit(low) cells died within 10 days whereas all six tertiary recipients originally reconstituted with Lin-/CD71-/class I(high)/c-kit(<low) cells showed donor (Ly5.1+)-derived cells in their peripheral blood. In the single tertiary recipient that was killed, donor-derived T cells, B cells, macrophages, and granulocytes also were detected in several major hematolymphoid organs. The remaining five mice continue to survive more than 6 months after the tertiary bone marrow transplantation.

Animals↗
PubMed1997

Induction of cyclin-dependent kinase inhibitor, p21WAF1, by treatment with 3,4-dihydro-6-[4-(3,4)-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinoline (vesnarinone) in a human salivary cancer cell line with mutant p53 gene.

It has been found by PCR-SSCP analysis and direct DNA sequencing that a human salivary adenosquamous carcinoma-forming cell line, TYS, has a mutant p53 gene at codon 281Asp-->His. When TYS cells were treated with a differentiation-inducing agent, vesnarinone, cellular proliferation was significantly inhibited on the basis of MTT assay. In addition, it has been found by Northern blotting and/or immunoblotting that expression of p21WAF1 and transforming growth factor-beta (TGF-beta) is up-regulated by treating TYS cells with vesnarinone. TGF-beta 1 alone also induced p21WAF1 expression in TYS cells. Moreover, it has been shown by ELISA that the treatment of TYS cells with vesnarinone results in the enhanced generation of latent TGF-beta 1. The expression of TGF-beta receptor (T beta R), including T beta R-I, T beta R-II and T beta R-III, on TYS cells was detected by affinity cross-linking using 125I-TGF-beta 1 and addition of active TGF-beta 1 into serum-free culture medium inhibited the growth of TYS cells in a concentration-dependent manner. These findings suggest that vesnarinone might directly induce expression of p21WAF1 gene in TYS cells, the product of which may be associated with the inhibition of cell growth and induce differentiation.

Antineoplastic Agents↗
PubMed1997

Induction of c-kit molecules on human CD34+/c-kit < low cells: evidence for CD34+/c-kit < low cells as primitive hematopoietic stem cells.

c-kit, a receptor for stem cell factor, has been widely accepted as a distinctive marker for hematopoietic stem cells. However, the level of c-kit expression on pluripotent hematopoietic stem cells is still controversial in mice and humans. We purified CD34+/c-kit < low cells (phenotypically c-kit-negative but only detectable at the message level) from human cord blood and examined their maturational steps in relation to the expression of c-kit molecules. When the CD34+/c-kit < low cells were cultured with cytokines (flt 3 ligand, interleukin 6 and interleukin 7) plus immobilized anti-CD34 monoclonal antibody (to crosslink CD34 molecules), c-kit molecules were clearly induced within 24 h. The c-kit expression gradually increased until day 8. When CD34+/c-kit(low) or CD34+/c-kit+ cells that had been induced from CD34+/c-kit < low cells were resorted and recultured using a methylcellulose culture system, they showed the same colony-forming ability as the freshly isolated CD34+/c-kit(low) or CD34+/c-kit+ cells, respectively. Furthermore, CD34+/c-kit < low cells have a similar hematopoietic potential to CD34+/c-kit(low) cells in assays for long-term culture initiating cell and colony-forming unit culture generated from long-term cultures. These findings suggest that CD34+/c-kit < low cells mature into CD34+/c-kit(low) and CD34+/c-kit+ cells, and acquire the reactivity to various humoral hematopoietic stimuli. Moreover, CD34+/c-kit < low cells showed a low level of rhodamine 123 retention, suggesting that CD34+/c-kit < low cells have multidrug resistance. Therefore, the CD34+/c-kit < low cells without colony-forming unit-granulocyte-erythroid-macrophage-megakaryocyte activity are also a pluripotent hematopoietic stem cell population, and the expression of c-kit on c-kit < low cells is the first maturational step of hematopoiesis.

Antigens, CD34↗
PubMed1997

Ultrastructural findings of the macula utriculi in a case of a petrous apex cholesteatoma: a comparison with findings in a patient with an acoustic neuroma.

The morphological characteristics of the vestibular sensory cells of the macula utriculi obtained during surgery in a patient with a petrous apex cholesteatoma were examined using scanning and transmission electron microscopy. Findings were compared to cells studied in a patient with acoustic neuroma. Scanning electron microscopy showed that compared to the apparently normal cells in the acoustic neuroma case, most sensory cells in the cholesteatoma case had large cuticular plates, irregular locations of cilia and no clear polarizations. Supporting cells showed profuse short microvilli on the whole surface. With transmission electron photomicrographs, type I hair cells were not seen and certain morphological changes were observed in type-II-like cells and supporting cells. We presume that the degenerative changes in the vestibular epithelia were due to circulatory disturbances and/or direct pressure applied to the vestibular nerve at the internal auditory canal, with subsequent involvement of the macula utriculi.

Acoustic Maculae↗
PubMed1997

Predominant expression of the src homology 2-containing tyrosine phosphatase protein SHP2 in vascular smooth muscle cells.

src homology 2 (SH2)-containing protein-tyrosine phosphatase SHP2 is known to transduce positive signals from activated receptor protein-tyrosine kinases such as platelet-derived growth factor receptor (PDGFR) beta and insulin receptor. Here, we demonstrate the physiological expression of SHP2 in rats. In northern and western blot analyses, SHP2 expressions were recognized in all tissues, but their expression levels varied significantly among tissues: it is lowest in the liver and kidney. Immunohistochemical staining and in situ hybridization showed SHP2 was expressed ubiquitously but predominantly in vascular smooth muscle cells (SMC). During the development of granulations. SHP2 was expressed predominantly in vascular SMC and also highly expressed in capillary cells. The functional associations of SHP2 with PDGFR beta, which transduces major growth signals in vascular SMC, identify a crucial function of SHP2 in blood vessels in consert with PDGFR beta.

Actins↗
PubMed1997

Induction of apoptotic cell death by direct-current treatment in human leukemic cell lines.

Exposure of human leukemic cell lines (HL-60, ML-1, U-937, MOLT-4, EOL-1) to short direct-current (d.c.) treatment induced apoptotic cell death, characterized by cell shrinkage and nuclear and internucleosomal DNA fragmentation. On the other hand, human peripheral blood lymphocytes and polymorphonuclear cells were relatively resistant to d.c. treatment, and did not show any clear nuclear and DNA fragmentation. The effect of d.c. was slightly reduced by calcium depletion, but was not significantly affected by catalase or by superoxide dismutase. The present data suggest that previously reported tumor regression activities of d.c. treatment might be due, at least in part, to its apoptosis-inducing activity.

Antioxidants↗
PubMed1997

Mediastinal lipoma: report of a case.

We experienced a case of mediastinal lipoma, which is considered to be relatively rare disease. A 3-year-old girl was referred to Gifu University hospital because of fever and an abnormal shadow on her chest X-ray. The chest X-ray clearly showed a well-delineated tumor shadow which seemed to oppress the diaphragm and the right atrium in the right lower lung area. A computed tomogram (CT) of the chest showed a homogeneous mass localized on the right diaphragm and adjoining the right anterior chest wall and heart. The mass showed a fat density measuring about -100 HU. Magnetic resonance imaging (MRI) showed a high-intensity mass which was almost the same level as the subcutaneous fat on both the T1-weighted and T2-weighted images. Thoracotomy was performed and a fatty tumor was found. It arose from the right side of the pericardium and adjoined the diaphragm, the anterior chest wall, and the thymus. There was no adhesion between the tumor and the surrounding organs. It was resected easily and its contents were yellowish and homogeneous. The patient made an uneventful recovery and was discharged 10 days after the operation. Light microscopy showed a lipoma consisting of mature adipose tissue and no malignancy was found.

Child, Preschool↗
PubMed1997

Induction of nonspecific cross-reacting antigen mRNA by interferon-gamma and anti-fibronectin receptor antibody in colon cancer cells.

Nonspecific cross-reacting antigen (NCA), a member of the carcinoembryonic antigen (CEA) family, shows increased expression levels in colorectal cancer tissues. To elucidate the mechanism, we observed the effect of interferon (IFN)-gamma on the expression level of NCA mRNA in colon cancer cell lines by quantitative reverse transcriptase-polymerase chain reaction assay. IFN-gamma induced NCA mRNA in three of four cell lines tested. The effect of anti-fibronectin receptor (FnR) antibody on the expression of NCA mRNA was then examined in the same manner. Colo201 and DLD-1 cells showed an increased expression level of NCA mRNA after stimulation with the antibody. On flow cytometry, FnR was expressed in only two, Colo201 and DLD-1, of the five cell lines tested. These findings indicate that IFN-gamma and anti-FnR antibody induce NCA mRNA in cultured colon cancer cell lines, suggesting that inflammatory response and cell-to-extracellular matrix interaction may be related to the increased expression of NCA mRNA in colorectal cancers in vivo.

Antigens, Neoplasm↗
PubMed1997

Quantitative analysis of cytokine mRNA expression in peripheral blood mononuclear cells following treatment with interleukin-2.

After activation with interleukin-2 (IL-2), peripheral blood mononuclear cells (PBMC) have been reported to induce the expression of mRNA coding various cytokines, including interleukin(IL)-1alpha, -1beta and tumor necrosis factor alpha (TNF alpha). We examined the cytokine mRNA expression of PBMC following treatment with IL-2 in vitro and in vivo by a quantitative method using the reverse transcription/polymerase chain reaction (RT-PCR). After stimulating PBMC with IL-2 in vitro, peak levels of IL-1alpha mRNA were reached between 3 h and 12 h, and thereafter declined. The IL-1beta expression increased, with levels peaking at 1-6 h and, had decreased by 96 h. The expression of TNF alpha was elevated both 1-3 h and 24-48 h after stimulation. The peak levels of IL-1alpha and -1beta mRNA and the early elevation of TNF alpha mRNA mainly accounted for the cytokine mRNA expression in adherent cells; however, the late induction of TNF alpha mRNA was observed in nonadherent cells. In patients with advanced carcinoma, the IL-1alpha and -1beta mRNA expression were elevated after IL-2 treatment for 5 consecutive days, while the expression of TNF alpha mRNA also increased. These results indicate that the quantitative RT-PCR method appears to be useful for analyzing the cytokine mRNA expression of PBMC after treatment with IL-2.

Carcinoma↗
PubMed1997

The possible role of remnant-like particles as a risk factor for sudden cardiac death.

Postmortem plasma lipid and lipoprotein levels were analyzed in two groups of Japanese subjects who died suddenly and unexpectedly due to cardiac (n = 93) or non-cardiac (n = 26) causes. No individuals in either group had a significant medical or cardiac history. In this study, we measured plasma total cholesterol, triglycerides, VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol, and especially triglyceride-rich lipoprotein remnants. Triglyceride and apo E-rich remnant-like particles (RLP) were studied as a possible risk factor for sudden cardiac death in relation to the progression of coronary atherosclerosis. The receiver-operating characteristic curve (ROC) analysis showed that RLP-TG was the most significant risk factor for sudden cardiac death among the lipids and lipoproteins and RLP-C was the best predictor for coronary atherosclerosis. HDL-C and LDL-C levels were within normal limits in the majority of the cases and did not appear to relate to the sudden cardiac death. Apo E phenotyping was performed for the detection of the genetic background in the lipid metabolism. The frequency of the Apo E3/3 (wild type) phenotype, which closely relates with the remnant metabolism, was significantly reduced in the sudden cardiac death group. Our study on the postmortem plasma lipid analysis suggested that RLP-C and RLP-TG are the best risk predictor for coronary atherosclerosis and sudden cardiac death, respectively.

Adult↗
PubMed1997

Osteopathia striata, short stature, and characteristic facies: a previously unknown skeletal dysplasia.

UNLABELLED: We report two sporadic cases of a hitherto undescribed skeletal dysplasia with short stature and characteristic facies. The present patients, a 6-year-old girl and a 15-year-old boy, were almost equally affected. Craniofacial anomalies included a sloping forehead, bitemporal bulging, sparse medial eyebrows, a prominent nasal bridge, hypertelorism, proptosis, a beaked nose, hypoplastic alae nasi and a pointed chin. Shallow orbits, short anterior cranial fossae and bitemporal bossing found on skull radiograph corresponded with the facial dysmorphism. Thickening of the dorsum sellae was another hallmark in the skull. Skeletal survey revealed mild osteopenia, interpediculate narrowing of the lumbar spine with short neural arches and, most important, osteopathia striata of the long tubular bones. There was no sclerosis of the craniofacial bones. The clinical and radiological findings in the present patients were overall inconsistent with those of previously known skeletal dysplasias and congenital malformation syndromes, which possess osteopathia striata as a cardinal feature. CONCLUSION: The unique clinical and radiological constellation of our patients constitutes a hitherto unknown bone dysplasia.

Adolescent↗
PubMed1997

Force generation in the outer hair cell of the cochlea.

The outer hair cell of the mammalian cochlea has a unique motility directly dependent on the membrane potential. Examination of the force generated by the cell is an important step in clarifying the detailed mechanism as well as the biological importance of this motility. We performed a series of experiments to measure force in which an elastic probe was attached to the cell near the cuticular plate and the cell was driven with voltage pulses delivered from a patch pipette under whole-cell voltage clamp. The axial stiffness was also determined with the same cell by stretching it with the patch pipette. The isometric force generated by the cell is around 0.1 nN/mV, somewhat smaller than 0.15 nN/mV, predicted by an area motor model based on mechanical isotropy, but larger than in earlier reports in which the membrane potential was not controlled. The axial stiffness obtained, however, was, on average, 510 nN per unit strain, about half of the value expected from the mechanical isotropy of the membrane. We extended the area motor theory incorporating mechanical orthotropy to accommodate the axial stiffness determined. The force expected from the orthotropic model was within experimental uncertainties.

Animals↗
PubMed1997

Effect of diamide on force generation and axial stiffness of the cochlear outer hair cell.

We found that diamide, which affects spectrin, reduces the axial stiffness of the cochlear outer hair cell, the cylindrically shaped mechanoreceptor cell with a unique voltage-sensitive motility. This effect thus provides a means of examining the relationship between the stiffness and the motility of the cell. For measuring axial stiffness and force production, we used an experimental configuration in which an elastic probe was attached to the cell near the cuticular plate and the other end of the cell was held with a patch pipette in the whole-cell recording mode. Diamide at concentrations of up to 5 mM reduced the axial stiffness in a dose-dependent manner to 165 nN per unit strain from 502 nN for untreated cells. The isometric force elicited by voltage pulses under whole-cell voltage clamp was also reduced to 35 pN/mV from 105 pN/mV for untreated cells. Thus the isometric force was approximately proportional to the axial stiffness. Our observations suggest a series connection between the motor and cytoskeletal elements and can be explained by the area motor model previously proposed for the outer hair cell.

Animals↗
PubMed1997

Relation of enhanced secretion of active matrix metalloproteinases with tumor spread in human hepatocellular carcinoma.

BACKGROUND & AIMS: Matrix metalloproteinases have been implicated in invasion and metastasis of various human malignant tumors, but its role in human hepatocellular carcinoma has not been characterized in detail. The aim of the present study was to examine the secretion and activation of metalloproteinases in liver tissues from patients with hepatocellular carcinoma and evaluate its relationship with clinicopathologic characteristics. METHODS: Activity of metalloproteinases was measured in 30 surgical specimen pairs of human primary hepatocellular carcinoma and adjacent nontumoral liver and in five cultured human hepatoma cell lines using zymography. A comparison of this activity with clinicopathological features was made. RESULTS: In the liver tissues, enhanced secretion of active forms of gelatinase A and matrilysin was associated with portal venous invasion (P < 0.05, respectively), intrahepatic metastasis (P < 0.05, respectively), and recurrence within the first postoperative year (P < 0.01 and P < 0.05, respectively). Enhanced messenger RNA expression for membrane type 1-matrix metalloproteinase was observed in 22 of 30 cases and associated with capsule invasion and the activation of progelatinase A (P < 0.05, respectively). CONCLUSIONS: Active gelatinase A, active matrilysin, and membrane type 1-matrix metalloproteinase may play an important role in tumor spread of human hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1997

Clinical experience of trabeculotomy for the surgical treatment of aniridic glaucoma.

OBJECTIVE: The purpose of this study is to determine the efficacy of initial trabeculotomy in the patient with aniridic glaucoma. DESIGN: Clinical charts were reviewed. PARTICIPANTS: Twenty-nine eyes of 16 patients with aniridia were studied. INTERVENTION: Glaucoma surgery was performed. As an initial procedure, trabeculotomy was performed in 12 eyes, other surgery was performed in 17 eyes (trabeculectomy, 5; goniotomy, 5; other, 7). MAIN OUTCOME MEASURES: Success was defined as an intraocular pressure (IOP) of 21 mmHg or lower, and no further surgery was performed. RESULTS: Ten (83%) of 12 eyes obtained IOP control after first (6 eyes) or second (4 eyes) trabeculotomy with a mean follow-up period of 9.5 years. Five eyes maintained visual acuity of 20/40 to 20/200. No serious complications were found after trabeculotomy. Three (18%) of 17 eyes were controlled with the first glaucoma surgery other than trabeculotomy (goniotomy, trabeculectomy, trabeculectomy combined with trabeculotomy, and Molteno implant). Good IOP control was obtained in 8 (47%) of 17 eyes after several surgeries with a mean follow-up period of 10.4 years. Four of 17 eyes became phthisical. CONCLUSION: This study suggests that trabeculotomy is the preferred initial operation for uncontrolled glaucoma with aniridia.

Adolescent↗
PubMed1997

Albuminuria is directly associated with increased plasma PAI-1 and factor VII levels in NIDDM patients.

Increased plasma plasminogen activator inhibitor type 1 (PAI-1), coagulation factor VII (FVII) and fibrinogen levels have been recognized as risk factors for cardiovascular disease. Because a substantially high incidence of cardiovascular disease has been reported in diabetic patients with nephropathy compared with those without nephropathy, we measured plasma levels of PAI-1, FVII activity and fibrinogen in non-insulin-dependent diabetic patients (NIDDM) with normoalbuminuria (without nephropathy), microalbuminuria (incipient nephropathy) and macroalbuminuria (overt nephropathy). PAI-1 and FVII levels were significantly increased in NIDDM with overt nephropathy compared with NIDDM without nephropathy. Fibrinogen levels were comparable between the patients with normo-, micro- and macro-albuminuria. Univariate regression analysis indicated that PAI-1 and FVII levels were significantly correlated with the albumin excretion rate (AER) in urine. PAI-1, FVII and fibrinogen levels were significantly correlated with the degree of insulin resistance estimated by the steady state plasma glucose concentration (SSPG) during the continuous infusion of glucose, insulin and octreotide. PAI-1 levels were correlated with plasma triglyceride (TG) levels. Multiple regression analysis revealed that AER was significantly associated with PAI-1 and FVII levels, whereas TG lost significant correlation with PAI-1 when AER, SSPG and plasma TG were entered as independent variables. SSPG retained an independent correlation with fibrinogen, PAI-1 and FVII levels. These results suggest that elevated plasma levels of PAI-1 and FVII in NIDDM patients with nephropathy are directly associated with renal damage, whereas insulin resistance widely regulates hemostatic components in NIDDM patients, irrespective of the presence of nephropathy.

Albuminuria↗