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Biomedical subjects

M Adachi

Publications and source records attributed to M Adachi.

At least 307 records · Page 17Linked to original sources
PubMed1997

[Effects of SDZ ISQ 844, a cyclic nucleotide phosphodiesterase isozyme type III/IV inhibitor, on the release of histamine from human peripheral leukocytes].

We studied the effects of SDZ ISQ 844, a cyclic nucleotide phosphodiesterase (PDE) isozyme type III/IV inhibitor, and salbutamol on the release of histamine from activated human peripheral leukocytes. We stimulated the leukocyte suspensions with calcium ionophore A23187 (Ca-I, 10(-6 M) accompanied with SDZ ISQ 844 (10(-7) M, 10(-6) M, 10(-5) M), salbutamol (10(-7) M, 10(-6) M, 10(-5) M) and combination of SDZ ISQ 844 and salbutamol (10(-7) M, 10(-6) M, 10(-5) M), and measured the levels of histamine in the supernatant fluid and total cyclic AMP levels in the leukocyte suspensions. The increase of histamine levels induced by Ca-I was significantly inhibited by SDZ ISQ 844 (10(-6) M, 10(-5) M) in a dose-dependent manner (p < 0.05, p < 0.01). Salbutamol at the concentration until 10(-5) M did not inhibit the increase of histamine levels. Combination of SDZ ISQ 844 and salbutamol significantly inhibited the increase of histamine levels (10(-6) M, 10(-5) M) in a dose-dependent manner (p < 0.05, p < 0.01). The inhibition of the histamine release by SDZ ISQ 844 (10(-5) M was enhanced significantly by salbutamol (10(-5) M) (p < 0.05). Total cyclic AMP levels in the leukocytes suspensions increased significantly by SDZ ISQ 844 (10(-5) M) and combination of SDZ ISQ 844 and salbutamol (10(-6) M, 10(-5) M) in a dose-dependent manner (p < 0.05, p < 0.01). The increase of cyclic AMP levels by SDZ ISQ 844 (10(-5) M) was enhanced by salbutamol significantly (p < 0.01). These results suggest that selective inhibition of PDE isozyme type III/IV protects the release of histamine from human activated leukocytes in connection with intracellular cyclic AMP levels and the protection is enhanced by beta-agonist.

Adrenergic beta-Agonists↗
PubMed1997

[Determinants associated with location of terminal care in the cancer patient].

Data relating to the place where terminal care was provided and where death was experienced were extracted from the charts of 100 terminally ill cancer patients who had been admitted to the first free-standing hospice in Japan. Of these 100 patients who died between October 1993 and May 1995, 91 patients died in the hospice, five in the hospital, and only four at home. To clarify factors associated with the place where terminal care was provided to the cancer patient, the length of stay at home during the last 30 days of life was examined. We divided the 100 cases into two groups, group 1 comprising 60 cases who had spent less than seven days at home, group 2 comprising 40 patients who had spent seven days or more at home, and compared these two groups in terms of age, sex, diagnosis, strength of pain, morphine dosage, use of intravenous fluids, performance status, place of care before admission to hospice, awareness of having cancer, distance from the hospice, the number of family members in the household, and housing environment. Using multiple logistic regression, three factors are identified as significantly impedimental to staying at home: high morphine dosage (> 60 mg daily oral morphine equivalence), direct transfer from hospital to hospice, and living on the second or upper floors in an apartment building. The data suggest that the development of palliative home care and improvement of housing environment may enable cancer patients to spend more time at home during their terminal phase.

Adult↗
PubMed1997

Induction of apoptosis in megakaryocytic leukemia cell lines by MX2, a morpholino anthracycline.

Leukemia with megakaryocytic involvement has a poor prognosis. MX2 is a new morpholino anthracycline that is effective against various leukemic cell lines. This study examined the antitumor activity of MX2 against human megakaryocytic cell lines, including CMK, CMK11-5, MEG-01, and UT-7, and investigated the role of apoptosis in the cytotoxicity of this drug. To quantify the extent of apoptosis induced by MX2, we used the in situ terminal deoxynucleotide transferase assay and the histone-associated DNA fragmentation assay. The cytotoxic effect of MX2 on CMK cells was reduced by various inhibitors of apoptosis. To our knowledge, this is the first report showing that apoptosis is involved in the killing of megakaryocytic cell lines by an antileukemic agent. We suggest that MX2 may be useful for the treatment of megakaryocytic leukemia.

Antibiotics, Antineoplastic↗
PubMed1997

[Chemotactic activity of human peripheral eosinophils toward leukotriene E4].

We studied the chemotactic activity of isolated human peripheral eosinophils toward leukotriene (LT) E4. We obtained eosinophil suspensions by the method of CD16 negative selection. Eosinophil chemotactic activities toward platelet activating factor (PAF, 10(-6) M) and LTE4 (10(-7) M, 10(-6) M, 10(-5) M) were studied using a modified Boyden Chamber method. Eosinophils migrated significantly toward PAF and LTE4 (10(-7) M, 10(-6) M). The chemotactic activity toward LTE, was most potential at 10(-6) M. These results suggest that LTE4 is an eosinophil chemoattractant.

Chemotaxis, Leukocyte↗
PubMed1997

[Are directional coronary atherectomy and Palmaz-Schatz stent more efficacious than conventional balloon angioplasty for treating de novo coronary artery lesions?].

It is unclear whether new devices such as directional coronary atherectomy (DCA) or Palmaz-Schatz stent implantation improve long-term outcomes compared with conventional balloon angioplasty in patients with stable angina and de novo coronary artery lesions of type A or type B except for complete occlusive lesions investigated by the American College of Cardiology/American Heart Association task force on percutaneous transluminal coronary angioplasty. A total of 146 patients with stable angina and simple lesions were assigned to either conventional balloon angioplasty (62 patients), DCA (50 patients), or Palmaz-Schatz implantation (34 patients). The acute results and late outcomes were assessed by coronary angiography. The results of the three procedures were similar with respect to procedural success and complications. Patients who underwent stenting or DCA had a larger immediate increase in the diameter of the lumen and a larger luminal diameter immediately after the procedure than those who underwent balloon angioplasty. At six months follow-up, the patients treated by stenting continued to have a larger luminal diameter and a lower rate of restenosis than those treated with balloon angioplasty (2.30 +/- 0.66 vs 1.85 +/- 0.83 mm, p < 0.005; 5.9% vs 29%, p < 0.05) and DCA (2.30 +/- 0.66 vs 1.90 +/- 0.96 mm, p < 0.05; 5.9% vs 24%, NS). The patients treated with balloon angioplasty had a smaller late loss than those treated with DCA or Palmaz-Schatz stent. The patients treated with DCA had a larger loss index than those treated with balloon angioplasty or Palmaz-Schatz stent. Stenting was a significant factor in decreasing the rate of restenosis by logistic regression analysis, compared with balloon angioplasty. The angiographic outcomes were better in patients who received a stent than in those who received other treatments. This study suggests that even lesions stable for treatment by balloon angioplasty and DCA can also be treated with Palmaz-Schatz stents.

Aged↗
PubMed1997

[Rapidly progressed chronic myelomonocytic leukemia associated with severe skin infiltration].

A 79-year-old man developed nodular skin eruption in his trunk in March 1995. He was diagnosed as CTCL and hospitalized to the department of dermatology and low dose VP-16 therapy was started. 6 months later, he was referred to our department because of severe melena. On admission, marked monocytosis was observed both in the bone marrow (43.6%) and peripheral blood (monocyte > 1,000/microliter). Skin biopsy showed infiltration of large mononuclear cells in the dermis and subcutaneous tissue. Thus a diagnosis of CMML with skin infiltration was made. Skin eruption developed over his entire skin and peripheral monocytes increased over 5,000/microliter. Chemotherapy was started and skin infiltration was slightly improved, but the disease developed into acute phase and he died 3 months after admission.

Aged↗
PubMed1997

[Comparative study of pre- and postoperative three-dimensional contrast-enhanced MRI with surgical finding in patients with hemifacial spasm].

The purpose of this study was to assess the utility of three-dimensional (3D) contrast-enhanced MRI in patients with hemifacial spasm. We performed preoperative MRI in 36 patients in whom microvascular decompression (MVD) was performed and postoperative MRI in 29. All MRI studies were obtained with a 1.5T MRI system using the spoiled GRASS (SPGR) method. In all patients, neurovascular compression of the facial nerve could be detected prior to MVD, and the rate of accuracy was 91.7%. Postoperative 3D-MRI was useful in confirming of displacement of the offending vessels and assessing of its severity.

Aged↗
PubMed1996

SPONASTRIME dysplasia: report on a female patient with severe skeletal changes.

We report on a 6-year-old girl with SPONASTRIME dysplasia, characterized by short-limbed dwarfism, a relatively large head, midfacial hypoplasia, a saddle nose, moderate deformities of the vertebral bodies, striated metaphyses, and normal intelligence. She showed severe skeletal changes including marked delay of epiphyseal ossification, evident metaphyseal dysplasia, and osteopathia striata more pronounced than in most of the previously reported patients with this disorder. The patient we describe and a male patient reported by Camera et al. [1994: Pediatr Radiol 24:322-324] are likely to represent the severely-affected end of the clinical spectrum of the disorder. These finding thus rule out the X-linked mode of inheritance of the disorder proposed by Camera et al. [1994: Pediatr Radiol 24: 322-324]. Alternatively, the two severely-affected patients may represent a variant form of the disorder. There is evidence that SPONASTRIME dysplasia is a genetically heterogeneous disorder.

Bone Diseases, Developmental↗
PubMed1996

Interleukin-2 (IL-2) upregulates BAG-1 gene expression through serine-rich region within IL-2 receptor beta c chain.

BAG-1 is a Bci-2-binding protein which functions in protection from apoptotic cell death. Here we provide evidence for interleukin-2 (IL-2)-mediated upregulation of BAG-1 expression. In hematopoietic cell line BAF-B03 F7 cells, gene transfer mediated expression of the IL-2R beta c chain is sufficient to confer proliferation and cell survival responses to IL-2. In these IL-2R beta c-expressing cells, BAG-1 mRNA was dramatically induced by IL-2. The IL-2-mediated induction of BAG-1 expression required the activation of tyrosine kinase(s) and was sensitive to rapamycin as the induction of bcl-2 expression was. Analysis of the transfectants which express mutant IL-2R beta c chains or mutant Janus family protein tyrosine kinase Jak3 lacking the kinase domain showed that the IL-2-mediated BAG-1 gene expression required the serinerich region within the IL-2R beta c chain, but Jak3 activation was dispensable. The signaling pathway for BAG-1 gene expression thus highly resembles that for bcl-2 gene expression, strongly suggesting that their induction shares the same signaling pathway. In addition, deletion of the serine-rich region led to loss of IL-2-mediated protection from apoptotic cell death. Taken together, these studies demonstrate that the serine-rich region of the IL-2R beta c chain mediates the coordinated expression of bcl-2 and BAG-1 genes, thereby contributing to suppression of apoptosis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Constitutively enhanced nbl expression is associated with the induction of internucleosomal DNA cleavage by actinomycin D.

Previous studies have found nbl expression to transiently rise and fall during glucocorticoid-induced thymic apoptosis. This induction of apoptosis is blocked by the transcriptional inhibitor actinomycin D. However, actinomycin D can trigger apoptosis in other cell types, e.g., HL-60 cells. This study found that internucleosomal DNA cleavage typical of apoptosis is induced by actinomycin D in cell lines such as HL-60 which constitutively express high levels of nbl above a certain "threshold." In contrast, "DNA ladder" formation was not induced by actinomycin D in cell lines with low constitutive nbl expression. Enhanced nbl expression therefore appears to be associated with apoptosis which is either blocked or induced by actinomycin D.

Amnion↗
PubMed1996

Synthesis and structure--activity relationships of fused imidazopyridines: a new series of benzodiazepine receptor ligands.

2-Arylimidazo[4,5-c]quinolines and analogous fused imidazopyridines were synthesized and evaluated as benzodiazepine receptor ligands. Affinity to the receptors was greatly affected by the bulkiness of the aryl group at the 2-position, compared to the pyrazoloquinolines such as CGS-9896. Derivatives with an isoxazole moiety at the 2-position showed high binding affinity and in vivo activity. In the imidazo[4,5-c]quinoline series, substitution at the 6-position decreased or abolished activity. Most derivatives with an unsubstituted isoxazolyl group showed antagonist or inverse agonist activity except for the 7-halo analogues, which exhibited agonist activity. On the other hand, 5-methylisoxazol-3-yl or 3-methylisoxazol-5-yl derivatives generally exhibited agonist activity. A similar substitution effect on the isoxazole moiety was observed in the imidazopyridines fused with a nonaromatic ring. From the detailed pharmacological evaluation, S-8510, 2-(3-isoxazolyl)-3,6,7,9-tetrahydroimidazo[4,5-d]pyrano++ +[4,3-b]pyridine monophosphate, possessing weak inverse agonist activity was selected as a therapeutic candidate for the treatment of some symptoms of senile dementia.

Animals↗
PubMed1996

Expression of dominant negative mutant SHPTP2 attenuates phosphatidylinositol 3'-kinase activity via modulation of phosphorylation of insulin receptor substrate-1.

To clarify the role of protein-tyrosine phosphatase (PTPase) containing Src homology 2 regions (SHPTP2) in insulin signaling, either wild-type or mutant SHPTP2 (delta PTP; lacking full PTPase domain) was expressed in Rat 1 fibroblasts overexpressing human insulin receptors. In response to insulin, phosphorylation of insulin receptor substrate 1 (IRS-1), IRS-1-associated PTPase activities and phosphatidylinositol (PI) 3'-kinase activities were slightly enhanced in wild-type cells when compared with those in the parent cells transfected with hygromycin-resistant gene alone. In contrast, introduction of delta PTP inhibited insulin-induced association of IRS-1 with endogenous SHPTP2 and impaired both insulin-stimulated phosphorylation of IRS-1 and activation of PI 3'-kinase. Furthermore, decreased content of p85 subunit of PI 3'-kinase was also found in mutant cells. Consistently, the insulin-stimulated mitogen-activated protein kinase activities and DNA synthesis were also enhanced in wild-type cells, but impaired in mutant cells. Thus, the interaction of SHPTP2 with IRS-1 may be associated with modulation of phosphorylation levels of IRS-1, resulting in the changes of PI 3'-kinase and mitogen-activated protein kinase activity. Furthermore, an impaired insulin signaling in mutant cells may be partly reflected in a decreased content of p85 protein of PI 3'-kinase.

Animals↗
PubMed1996

Correlation of KAI1/CD82 gene expression with good prognosis in patients with non-small cell lung cancer.

As part of our evaluation of members of the transmembrane 4 super-family as possible prognostic predictors, we performed a retrospective study on the expression of the recently identified KAI1 gene by tumors of the lung. This gene, which is identical to CD82, suppresses tumor metastasis of prostate cancer, and its decreased expression may be involved in malignant progression. We used reverse transcription-PCR to analyze tumor tissues from 151 lung cancer patients; 74 tumors were stage I, 17 were stage II, and 60 were stage III. Our results indicate that while 35 patients had tumors in which the KAI1/CD82 gene was conserved (positive), 116 patients had tumors with reduced gene expression (negative). The overall survival rate of patients with KAI1/CD82-positive tumors was significantly higher than that of patients with KAI1/CD82-negative tumors (77.4% versus 38.5%; P=0.002). Furthermore, the overall survival rate of patients with KAI1/CD82-positive adenocarcinoma was also much higher than that of individuals whose adenocarcinoma had reduced KAI1/CD82 expression (73.4% versus 27.1%;P=0.009). Multivariate analysis with the Cox regression model indicated that KAII/CD82 positivity correlated best with the overall survival rate, except for lymph node status. Our data suggest that high KAII/CD82 gene expression by tumors of the lung may be associated with a good prognosis. These findings complement our earlier studies on MRP-1/CD9, another member of the transmembrane 4 superfamily, whose reduced expression in non-small cell lung cancer appears to be a factor of poor prognosis. This set of observations suggests that assessment of the expression status of KAI1/CD82 and MRP-1/CD9 by tumors may provide prognostic information on the clinical behavior of lung cancer.

Age Factors↗
PubMed1996

Enhanced and accelerated lymphoproliferation in Fas-null mice.

Fas is a 45-kDa membrane protein that transduces an apoptotic signal. The mouse lymphoproliferation (lpr) mutation is a leaky mutation of Fas. In this study, we examined lymphocyte development in Fas-null mice generated by gene targeting. The Fas-/- mice progressively accumulated abnormal T cells (Thy1+, B220+, CD4-, and CD8-) and developed lymphadenopathy and splenomegaly, which were much more accelerated and pronounced than those in lpr mice. In addition, the Fas-null mice showed lymphocytosis, accompanied by lymphocytic infiltration in the lungs and liver. The number of apparently normal B cells also increased, and large amounts of immunoglobulins, including anti-DNA antibodies, were produced. Thymic clonal deletion, assessed by deletion of T cells reactive to mouse endogenous superantigens, was apparently normal in the Fas-/- mice, whereas the peripheral clonal deletion of mature T cells against a bacterial superantigen was impaired. These results suggested that Fas plays a decisive role in peripheral clonal deletion but not in negative selection in the thymus.

Animals↗