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Biomedical subjects

M Isobe

Publications and source records attributed to M Isobe.

At least 145 records · Page 8Linked to original sources

A case of primary cardiac lymphoma: utility of serum soluble interleukin-2 receptor for noninvasive diagnosis.

A 70-year-old woman was referred to us for the investigation of a tumor mass in the right sided of the heart. LDH and soluble interleukin-2 receptor (sIL2r) were elevated. She died one day after the initiation of radiation therapy because of intractable cardiogenic shock. Primary cardiac lymphoma was identified at autopsy. Measurement of serum sIL2r lead us to the antemortem diagnosis of the disease.

Aged↗

Amplification of the TCL1 flanking region at 14q32.1 with no TCL1 gene transcription in a patient with peripheral T cell lymphoma.

Cytogenetic and molecular-genetic characteristics in peripheral T cell lymphoma (PTL) have not been well defined, except for those in adult T cell leukemia/lymphoma (ATL/L). Translocations and inversions involving a chromosome band 14q32 were extremely common abnormalities reported in PTL and ATL/L. We studied the involvement of TCL1, a recently isolated gene located in 14q32.1, in tumor tissues from 20 patients with PTL including three with 14q32 translocations by two color fluorescent in situ hybridization (FISH) using two cosmid probes flanking the TCL1 gene. The two cosmid signals were separated in none of them, but much increased in number in one tumor without 14q32 translocation, indicating that the TCL1 genomic region was amplified in this tumor. Reverse transcription-polymerase chain reaction (RT-PCR), however, failed to detect the TCL1 transcript in the tumor. These findings suggest that an oncogene other than TCL1 may be located in 14q32.1, and its amplification may be involved in the neoplastic process of PTL.

Aged↗

Effects of monoclonal antibodies to adhesion molecules on eosinophilic myocarditis in Toxocara canis-infected CBA/J mice.

Eosinophilic myocarditis followed by fibrosis of the cardiac muscle was observed in addition to peripheral blood eosinophilia in CBA/J mice infected with Toxocara canis. The infected mice were used as an experimental model of eosinophilic endomyocarditis associated with hypereosinophilic syndrome. Effects of in vivo treatment with MoAbs to adhesion molecules on eosinophilic myocarditis were examined using this experimental model. Expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells of capillaries in myocardium were increased 1 and 2 weeks after infection. Infiltration of very late antigen (VLA)-4+ and/or CD11a+ cells into the cardiac muscles was also observed 1 and 2 weeks after infection. Infiltration of eosinophils into the heart was significantly suppressed by anti-CD18 MoAb and anti-VLA-4 MoAb, and focal fibrosis of the cardiac muscle was also significantly suppressed by combined administration of anti-CD18 and anti-ICAM-1 MoAbs. These results indicate that adhesion molecules may play important roles in eosinophilic myocarditis, and that blockade of interaction between adhesion molecules and their ligands may help to control it.

Animals↗

The role of ICAM-1/LFA-1 and VCAM-1/VLA-4 interactions on T helper 2 cytokine production by lung T cells of Toxocara canis-infected mice.

In order to study the effect of costimulatory signals on T helper type 2 (Th2) cytokine production, monoclonal antibodies (mAb) against cell adhesion molecules (CAM) were added to cells in culture obtained from the lungs of Toxocara canis (Tc)-infected mice followed by the determination of interleukin-5 (IL-5) and IL-4 in the supernatants of the culture. ES-stimulated IL-5 production in the supernatant of total lung cells was reduced by 25% when anti-intercellular adhesion molecule-1 (anti-ICAM-1) mAb, anti-CD11a mAb, or both anti-ICAM-1 and anti-CD11a mAb together were added to the culture. The addition of anti-CD18 mAb had no effects. Anti-vascular cell adhesion molecule-1 (anti-VCAM-1) mAb addition also reduced IL-5 production by 60%, although the addition of anti-very late activation antigen-4 (anti-VLA-4) mAb or both anti-VCAM-1 and anti-VLA-4 mAb together were less effective. In the case of anti-CD3 mAb stimulation, similar effects of mAb to CAM were observed. In contrast, IL-4 production induced by anti-CD3 mAb was reduced more markedly by the addition of either anti-ICAM-1 or anti-CD11a mAb than the combination of anti-VCAM-1 and anti-VLA-4 mAb. Similar effects of mAb to CAM were observed on the production of IL-5 and IL-4 by CD4+ T cells purified using a fluorescence-activated cell sorter. Coincubation with adherent cells was necessary for the significant production of IL-5 and IL-4 by CD4+ T cells. These results suggest that the VCAM-1/VLA-4 interaction is more important for IL-5 production by CD4+ T cells in the lungs of Tc-infected mice, and that the ICAM-1/lymphocyte function-associated antigen-1 interaction is more important for the production of IL-4.

Animals↗

Predominant implication of IL-5 in acute eosinophilic pneumonia: comparison with chronic eosinophilic pneumonia.

BACKGROUND: Acute eosinophilic pneumonia (AEP) is a rare disease with unknown etiology. To examine pathophysiology of AEP we measured the cell number of eosinophils and eosinophil active cytokines in the peripheral blood and bronchoalveolar lavage fluid (BALF) of AEP patients and compared the levels with those measured in chronic eosinophilic pneumonia (CEP) patients. METHODS: Cell number of eosinophils in peripheral blood and BALF from patients with AEP (n = 3) and CEP (n = 3) were measured. Eosinophil active cytokines in serum and BALF from the patients were measured using ELISA. RESULTS: Eosinophil cell number in peripheral blood was 274-1,377/mm3 in AEP and 526-2,500/mm3 in CEP. The percentages of BALF eosinophils were high in AEP and CEP. Eosinophilia disappeared after methylprednisolone pulse therapy (1 g for 3 days) in AEP, however the cell number of eosinophils gradually increased after methylprednisolone pulse therapy and then spontaneously decreased to within normal range without any further medication. The concentrations of IL-5 in AEP were very high in serum and in BALF, however the concentrations in CEP were low in serum and BALF. CONCLUSION: AEP is a disease in which eosinophil active cytokine IL-5 is predominantly involved; CEP is not. The factors involving eosinophil infiltration to inflammatory loci differ between AEP and CEP.

Acute Disease↗

Effects of intracellular cyclic AMP modulators on human eosinophil survival, degranulation and CD11b expression.

BACKGROUND: Brochial asthma is characterized by infiltration of inflammatory cells such as lymphocytes and eosinophils. Theophylline is one of the most widely used drugs in the therapy of bronchial asthma, and phosphodiesterase (PDE) inhibition is thought to be an important mechanism of its anti-inflammatory actions. However, the detailed effects of PDE inhibition on eosinophils still remain unclear. METHODS: Eosinophils in peripheral blood obtained from normal subjects and patients with mild off-season allergic rhinitis were purified using CD16 negative selection. The following effects of theophylline (nonselective PDE inhibitor), KF19514 (selective PDE IV inhibitor), mirlinone (selective PDE III inhibitor), procaterol (beta2-adrenoceptor agonist) and N6, 2'-O-dibutyryladenosine 3'5'-cyclic monophosphate (dB-cAMP; AMP analogue) on eosinophils were examined: (1) survival in the presence of interleukin-5, (2) degranulation by granulocyte/macrophage colony-stimulating factor (GM-CSF) or platelet-activating factor (PAF), (3) CD11b expression under GM-CSF or PAF stimulation and (4) intracellular cAMP level. RESULTS: Eosinophil survival was inhibited by theophilline, KF19514 or procaterol. GM-CSF- or PAF-induced degranulation was inhibited by theophylline, KF19514, procaterol or dB-cAMP. CD11b up-regulation by PAF was inhibited by theophylline, KF19514 or dB-cAMP, while GM-CSF-stimulated CD11b up-regulation was not significantly inhibited by any of the drugs tested. The levels of intracellular cAMP were increased by theophylline, KF19514 and procaterol. CONCLUSIONS: Intracellular cAMP is an important factor in the regulation of eosinophil biological functions. PDE IV inhibitors and beta2-agonists are suggested to be useful for the treatment of bronchial asthma through inhibition of eosinophil effector function.

Bucladesine↗

Successful stenting of bilateral renal artery stenosis due to fibromuscular dysplasia assessed by use of pressure guidewire technique: a case report.

An 18-year-old woman with renovascular hypertension had stenosis due to fibromuscular dysplasia (FMD) of the bilateral renal arteries, and this did not respond to conventional balloon angioplasty owing to marked elastic recoil. Implantation of Palmaz-Schatz stents resulted in successful dilation of the stenosis and remission of hypertension. Transstenotic pressure gradients were measured by use of a pressure-monitoring guidewire. It is suggested that stenting is a very useful adjunct to balloon angioplasty in the treatment of renal artery stenosis due to FMD.

Adolescent↗

New approaches to the management of acute and chronic cardiac allograft rejection.

There are still many problems to be faced in the field of heart transplantation. Acute and chronic rejection are still the major medical obstacles. In this review, we describe recent research in this field undertaken in our laboratory. The induced intercellular adhesion molecule-1 (ICAM-1) and MHC class II antigen resulting from rejection can be visualized in vivo by radioimmunoscintigraphy. This non-invasive method is sensitive for detecting early rejection and allows quantitative assessment of rejection. Short-term administration of monoclonal antibodies to ICAM-1 and leukocyte function-associated antigen-1 (LFA-1) results in an indefinite acceptance of cardiac allografts by induction of antigen-specific tolerance, as evidenced by acceptance of the secondary skin allografts. The characteristics and possible mechanisms of this tolerance induction are discussed. Immunohistopathologic features of graft coronary arteriopathy are shown. Adhesion molecules, cytokines, and growth factors are associated with intimal hyperplasia and phenotypic transformation of smooth muscle cells in the allograft coronary arteries. Dramatic reduction in this intimal hyperplasia was demonstrated by antisense gene therapy targeting cyclin-dependent kinase 2 kinase. We hope that these investigations will contribute to the improvement of the management of patients who undergo heart transplantation.

Acute Disease↗

Cardiac sarcoidosis mimicking hypertrophic cardiomyopathy: clinical utility of radionuclide imaging for differential diagnosis.

A 62-year-old woman with skin sarcoidosis was admitted to our hospital to ascertain whether she had cardiac involvement. Although she displayed no cardiac signs or symptoms, the electrocardiogram showed first-degree atrioventricular block, right bundle branch block with left anterior fascicular block, and giant negative T waves in the V3 lead. Echocardiography revealed marked hypertrophy localized in the basal portion of the interventricular septum (IVS) without systolic dysfunction, mimicking hypertrophic cardiomyopathy (HCM). Exercise thallium-201 myocardial imaging revealed redistribution in the anteroseptal region. Both gallium-67 (67Ga) and technetium-99m pyrophosphate (99mTc-PYP) scintigraphy revealed abnormal uptake in the myocardium. These findings disappeared after 2 months of steroid treatment. Reports of cardiac sarcoidosis mimicking HCM are rare. However, hypertrophy in the basal portion of the IVS is an important sign of early cardiac involvement in sarcoidosis. 67Ga and 99mTc-PYP scintigraphy were useful and necessary to differentiate this type of cardiac sarcoidosis from HCM.

Cardiomyopathies↗

Familial sick sinus syndrome with atrioventricular conduction disturbance.

A family with sick sinus syndrome is presented: a mother and her 2 daughters affected with sinus node dysfunction. Electrophysiological studies revealed abnormal atrioventricular conduction in the 2 daughters. All 3 individuals were implanted with a permanent pacemaker to relieve their symptoms. Endomyocardial biopsy from the right ventricle of one daughter showed disarrangement, degeneration, myocyte necrosis and interstitial fibrosis suggestive of myocardial disease.

Adult↗

Salicylic acid induces a cytosolic Ca2+ elevation in yeast.

Cytosolic free calcium ion concentration ([Ca2+]cyt) after a salicylic acid (SA)-stimulus was monitored in cells of the yeast Saccharomyces cerevisiae expressing apoaequorin, which constitutes a Ca(2+)-sensitive luminescent protein, aequorin, when combined with coelenterazine. SA induced a transient [Ca2+]cyt elevation that was dependent on the concentration of SA and pH of the SA solution. The SA-induced [Ca2+]cyt elevation was not reduced in Ca(2+)-deficient medium, suggesting that Ca2+ was mobilized from an intracellular Ca2+ store(s). Benzoic acid, butyric acid and sorbic acid did not induced a [Ca2+]cyt elevation.

Aequorin↗

[Dysphagia caused by ossification of the anterior longitudinal ligament associated with diffuse idiopathic skeletal hyperostosis: report of 2 cases].

Two cases of ossification of the anterior longitudinal ligament (OALL) associated with diffuse idiopathic skeletal hyperostosis (DISH) presenting as dysphagia are reported. DISH has long been regarded as a radiological entity manifesting flowing ossification adjacent to the anterior and lateral borders of at least four contiguous vertebral bodies, maintenance of disc spaces, and a dearth of bony ankylosis and erosion of the apophyseal and sacroiliac joints. In the majority of cases, this entity shows an innocuous clinical course, but the dysphagia shown in our cases has also been documented in previous literature. Case 1 was a 63-year-old male developing progressive dysphagia and rhinolalia. Cervical X-rays and CT showed flowing OALL in the entire cervical spine. MRI demonstrated displacement of the trachea and esophagus by this mass. There was OALL in the thoracic and lumbar spine. Case 2 was a 62-year-old male who had undergone removal of ossification of the posterior longitudinal ligament (OPLL) from C2 to C5. He developed dysphagia and myelopathy. Cervical X-rays and CT demonstrated projection of OALL as well as posterior osteophytes at C5/6. MRI suggested that OALL had caused dysphagia, and osteophytes deteriorated myelopathy. Removal of OALL was carried out in these two cases. In case 2, removal of the osteophytes and herniated disc was carried out at the same time. Postoperative course was unremarkable with improvement of symptoms. Treatment of dysphagia due to OALL is considered to be conservative. However, surgical decompression should be considered in cases of marked projection of OALL obstructing the esophagus as shown in our cases.

Deglutition Disorders↗

[Nutrition and cancer patients].

Nutritional therapy for cancer patients includes various objectives such as improvement of cachexia, elucidation of the mechanism of malnutrition, development of therapy for anorexia, nutrition support during chemotherapy or radiotherapy, and inhibition of tumor growth under controlled caloric intake. This review describes recent remarkable developments in nutritional therapy for cancer patients. Cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor which induce proteolysis and lipolysis are involved in the cause of malnutrition and cachexia in cancer patients. IL-1 also plays a significant role in the development of cancer anorexia via direct action in the brain. For anorexia therapy, progestogens have been shown to improve appetite and food intake in cancer patients. Moreover, glutamine supplementation improves the host protein metabolism without enhancement of tumor growth during chemotherapy. Among the effects of caloric intake on anticancer therapy, AO-90, a methionine-free intravenous amino acid solution, has been shown to increase the antitumor effect of 5-fluorouracil in clinical studies. From these observations, recent progress in nutritional therapy for cancer patients has been remarkable. Further study of nutritional therapy is required in order to maintain or improve the quality of life of cancer patients in the future.

Humans↗

Massive pericardial effusion in an adult case of congenital hypothyroidism due to a sublingual thyroid.

Acquired hypothyroidism is known to cause cardiac tamponade. However, pericardial effusion in cretinism in adulthood has rarely been reported. A 27-year-old dwarfish woman suffering from congestive heart failure was diagnosed with congenital hypothyroidism due to the presence of a sublingual thyroid. The patient had never received thyroid therapy until the time of diagnosis at age 27. Despite the existence of massive pericardial effusion, the patient had hypertension. Her metabolic abnormality responded dramatically to L-thyroxin. Pericardial effusion disappeared one year after the initiation of medical treatment.

Adult↗

Role of selectin-dependent adhesion in cardiac allograft rejection.

BACKGROUND: Selectins play important roles in the inflammatory responses by eliciting leukocyte rolling. The roles of E- and P-selectins in the acute rejection of cardiac allografts remain unclear. This study was designed to evaluate whether E- and P-selectins participate in the pathophysiology of heart rejection. METHODS: Heterotopic heart transplantation was performed in both mice and rats in full histoincompatibility combinations. Immunohistochemistry, flow-cytometry, and reverse transcriptase- polymerase chain reaction were performed to evaluate E-, P-selectin and sialyl Lewis X (SLeX) expression in rejecting cardiac allografts. The effects of short-term administration of monoclonal antibodies (mAbs) to E- and P-selectins on cardiac allograft survival were also evaluated. RESULTS: Significant prolongation of graft survival was observed in mice treated with either anti-E- or P-selectin mAbs, or both. The enhanced endothelial and mRNA expression of E- and P-selectins was observed in the rejecting cardiac allografts. Some graft- infiltrating mononuclear cells were double-stained with both anti-SLeX and anti-alphabetaT cell receptor mAbs. Flow-cytometric analysis of graft-infiltrating cells also showed enhanced SLeX expression. CONCLUSION: These results suggest that both P- and E-selectins are critically involved in the early development of acute heart rejection.

Animals↗