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Biomedical subjects

H Yotsumoto

Publications and source records attributed to H Yotsumoto.

At least 37 records · Page 2Linked to original sources

A rare case of cardiac sarcoidosis in a patient with progressive systemic sclerosis, Sjogren's syndrome, and polymyositis.

A 56-year-old woman with overlap syndrome of progressive systemic sclerosis (PSS), Sjogren's syndrome, and polymyositis is reported. She developed complete atrioventricular (AV) block and progressive bilateral hilar adenopathy, and was diagnosed as having sarcoidosis by histological examination of the hilar lymph nodes biopsied thoracoscopically. Although coexistence of one or two autoimmune diseases with sarcoidosis is not uncommon, coexistence of three or more autoimmune diseases with sarcoidosis is rare. To our knowledge, the described case is the first case in which the three above-mentioned autoimmune diseases were accompanied by myocardial sarcoidosis.

Cardiomyopathies↗

Hypometabolism and dipole localization in hemimegalencephaly: a case report.

A case of hemimegalencephaly was studied by means of neuroimaging (CT, MRI and PET) and magnetoencephalography (MEG). Hemimegalencephaly (HM) is a neuronal migration disorder. This is the first report of evaluation of HM with the use of PET and MEG from not only the morphological but also the functional point of view. PET with 11C-glucose showed a low radioactive concentration in the affected hemisphere, which suggested a metabolic deficit. MEG proved the epileptic foci existed mainly in the affected hemisphere, especially around a heterotopia and the pachygyric cortex, which was disclosed on MRI.

Brain↗

Detection of lymphomatous involvement of the lung by bronchoalveolar lavage. Application of immunophenotypic and gene rearrangement analysis.

We report three cases of pulmonary involvement of non-Hodgkin's lymphoma in which immunophenotypic or gene rearrangement analysis of bronchoalveolar lavage (BAL) cells demonstrated monoclonality of T- or B-cell lineage. The first patient had T-cell lymphoma and developed pulmonary lesions. Surface marker analysis of the BAL cells revealed that CD8-positive lymphoid cells were dominant and Southern blot analysis of T-cell receptor gene detected gene rearrangement demonstrating monoclonality of T-cell lineage. The second patient presented with diffuse micronodular shadows on chest radiograph. Marked B-lymphocytosis in BAL fluid prompted us to analyze their clonality. The third was a case in which recurrence of primary pulmonary lymphoma was suspected. In the second and third case, the finding of marked increase in the number of CD 19-positive B lymphocytes with a single class of light chains proved a monoclonal population in BAL cells. With the review of other cases in our study and the relevant literature, we conclude that the clonal analysis of BAL cells is helpful in establishing the diagnosis of pulmonary involvement of T- or B-cell lymphoma.

Adult↗

Erythromycin promotes monocyte to macrophage differentiation.

Recent reports have suggested that long-term administration of erythromycin (EM) appears to ameliorate some of chronic inflammatory processes where macrophages and lymphocytes play important roles. Our study was initiated to examine the effect of EM on monocyte-macrophage lineage in vitro. EM (1 approximately 100 micrograms/ml) significantly increased the number of adherent monocyte-derived macrophages after 7 days of culture. The combination of EM and macrophage colony stimulating factor (M-CSF) synergistically increased the number of monocyte-derived macrophages, while the combination of EM and granulocyte-macrophage colony stimulating factor exerted an additive effect. Culture with EM induced the expression of a surface antigen CD71, one of the activation markers of macrophages as compared with control cultures. The combination of EM plus M-CSF significantly enhanced H2O2-producing capacity of those cells as compared with M-CSF alone. A differentiation process of monocytoid THP-1 cells was also augmented by EM. These results indicate that EM promotes differentiation of human monocyte-macrophage lineage, altering their functions.

Antigens, CD↗

[Efficacy of PCR-microwell plate hybridization method (Amplicor Mycobacterium) for detection of M. tuberculosis, M. avium and/or M. intracellulare in clinical specimens].

Recently, a new kit to detect and identify mycobacteria in clinical specimens was developed by Japan Roche Co. Limited. The new method is based on amplification of DNA of mycobacteria in clinical specimens by PCR and hybridization of amplified DNA by microwell plate hybridization method, which is the "Amplicor Mycobacteria, Roche, (AMP-M)". Cooperative study was organized with 15 tuberculosis hospitals and institutions throughout Japan, and 349 clinical specimens from newly admitted tuberculosis patients and/or suspects were collected during July and August, 1993. All the specimens were examined by smear microscopy (Ziehl-Neelsen's staining), culture on Ogawa egg media, culture on variant 7H9 liquid media and by AMP-M. Excluding 25 specimens which had failed to identify the species of mycobacteria because of contamination, disability to multiply on the transplanted solid media and so on, the results of the examinations in 324 specimens consisting of 167 specimens from previously untreated cases and those of 157 specimens from previously treated cases were analysed. Main results obtained were as follows; 1. Of 70 smear positive specimens from previously untreated cases, culture positive on Ogawa media and 7H9 media, and by AMP-M positive were 59 (84.3%), 61 (87.1%) and 66 (94.3%), respectively. Of 97 smear negative specimens, culture positive were 20 (20.6%), 22 (22.7%) and 27 (27.8%), respectively. The AMP-M showed the highest positive rate in both groups. 2. The sensitivity and the specificity of AMP-M in previously untreated cases were calculated by assuming that positive on Ogawa and/or variant 7H9 media is "positive". The sensitivity was 95.8% (68/71) and the specificity was 94.8% (91/96) for M. tuberculosis in previously untreated cases. The sensitivity and the specificity for M. avium and M. intracellulare were all 100%, although the numbers observed were small. 3. So-called false positive of the AMP-M were observed in 5 cases out of 96 culture negatives on both Ogawa and variant 7H9 media. However, all 5 cases were positive by repeated AMP-M, 3 become culture positive later, and another 2 showed clinical findings consistent with tuberculosis. Hence, the authors considered that the false positive rate of the AMP-M method is to be very low in previously untreated cases. 4. Of 86 smear positive cases with history of previous chemotherapy, the positive culture on Ogawa media, variant 7H9 media and that by AMP-M method were 64 (74.4%), 77 (89.5%) and 85 (98.8%), respectively. In the smear negative cases, culture positive was 10 out of 71 (14.1%), 13 (18.3%) and 24 (33.8%), respectively.

DNA, Bacterial↗

[Development of coding system for respiratory diseases and its application to classifying cases reported in the Japanese Journal of Thoracic Diseases].

We developed a coding system for respiratory diseases and related conditions for computer-aided analyses of these diseases. It is a one-axis alphanumeric system with a list of three-character categories and additional digits separated by a decimal point for subcategories. Respiratory and related diseases are categorized into eight groups; diseases of (1) the lung and airway, (2) the pleura, (3) the mediastinum, (4) the diaphragm, (5) the chest wall, (6) the heart and cardiovascular system, (7) the esophagus, and (8) clinical conditions predisposing to pulmonary disease. The first character, a letter from the A to G, represents a major disease category of (1) to (7) and X that of (8); and subdivisions are shown in the second position using the numbers from 0 to 9. Further subdivisions are provided in the third position also using numbers. Actual coding was done on case reports which appeared in the Japanese Journal of Thoracic Diseases from 1973 to 1993, and all cases were coded properly. The system is expected to prove useful in computer aided analyses of respiratory diseases.

Computers↗

Antilymphocytic activity of erythromycin distinct from that of FK506 or cyclosporin A.

Erythromycin (EM), a macrolide antibiotic has been recently reported to depress the extent of inflammation irrespective of its antimicrobial action. Our study was initiated to examine the effect of EM on T cell proliferation in vitro, since other macrolide antibiotics FK506 and rapamycin (RAP) have been well known to possess strong immunosuppressive or anti-inflammatory potential. EM had a suppressive effect on the proliferative response of human lymphocytes stimulated with mitogens and antigens, while EM had no effect on concanavalin A (Con A)-induced interleukin-2 (IL-2) production or IL-2R alpha (CD25) expression. Delayed addition of EM after the first 48 hours of mitogenic stimulation did suppress IL-2-dependent proliferation of Con A blasts, whereas pretreatment with EM for the first 48 hours of stimulation did not impede the subsequent IL-2-dependent proliferation of obtained blast cells. The results indicate that EM suppresses T cell proliferation at a late stage in the activation process by impairing their response to IL-2. This antilymphocytic action of EM was quite distinct from that of FK506 or cyclosporin A (CsA) but was similar to that of RAP. Unlike RAP, however, EM did not antagonize FK506-induced suppression but potentiated the action of FK506 and CsA. The addition of an enteric hormone motilin, a receptor of which was previously found to be occupied by EM, unaffected the lymphocyte proliferation and the subsequent EM-induced suppression. These data suggest that EM operates through an undefined mechanism probably distinct from that of FK506, CsA, RAP or motilin.

Antigens↗

Effects of an immunosuppressant, FK506, on interleukin 1 alpha production by human macrophages and a macrophage-like cell line, U937.

A recently discovered immunosuppressive agent, FK506, has been shown to be effective primarily as an inhibitor of T cell responses in vitro, but little is known about its effects on accessory cell function. This study was undertaken to determine the effect of FK506 on interleukin 1 (IL-1) production by macrophages, by using a sensitive and specific enzyme-linked immunosorbent assay. FK506 partially suppressed IL-1 alpha release, from macrophage-like U937 cells stimulated with phorbol myristate acetate and from human monocytes and alveolar macrophages activated with lipopolysaccharide, in a dose-dependent manner. Moreover, it was indicated that FK506 suppressed not only IL-1 release but also IL-1 synthesis itself, by measurement of cell-associated IL-1 alpha of U937 cells. The optimal concentrations of FK506 for suppressing IL-1 alpha did not affect cell viability or proliferation, and were 10- to 100-fold lower than those of cyclosporin A. It is concluded that FK506 affects macrophage physiology, suppressing IL-1 alpha production significantly. Thus, FK506 has the potency to act on non-T cells and the effect on macrophages may play an additional role in preventing graft rejection.

Anti-Bacterial Agents↗

[Magnetoencephalographic studies on spike foci using a 37-channel biomagnetometer system].

We report the results of a clinical trial of Magnetoencephalography (MEG) on spike foci in patients with epilepsy, which was performed from December 1990 to June 1991 at The University of Tokyo Hospital. Fifty patients with focal epilepsy; 26 primary epilepsy, 24 secondary epilepsy (7 brain tumor, 4 arteriovenous malformation, 4 encephalitis, 3 porencephaly, 2 arachnoid cyst, 1 brain abscess, 1 hemimegaloencephaly, 1 Lance-Adams syndrome, 1 hygroma), and ten normal subjects were enrolled in this study. MEG data were recorded using a 37-channel biomagnetometer system SMI-1001 (BTi Magnes, Biomagnetic Technologies, Inc., San Diego). A simultaneous 19-channel EEG recording with linked-ear reference was also obtained. The overall study was completed safely and none of the normal subjects showed abnormal paroxysmal MEG activity. Two patients showed interictal EEG spikes which would not have been noticed without first noting the presence of corresponding prominent MEG spikes. On the whole, the MEG signal seemed to have a wider frequency bandwidth than EEG. In most cases, the source localization predicted by MEG corresponded well with the EEG findings. The relative accuracy of MEG spike source localization was estimated to be within a cubic centimeter from the cases which showed tightly clustered localization of individual spikes. High-pass filtering reduced interference by superimposed slow wave activity, thereby improving the localization of spike sources. These results demonstrate that 37-channel biomagnetometer system could be a useful tool for analyzing epileptic spike sources.

Adolescent↗

Immunological quantitation and immunohistochemical localization of leukotriene A4 hydrolase in guinea pig tissues.

We prepared a highly specific polyclonal antibody against leukotriene (LT) A4 hydrolase using a recombinant human enzyme. Using this antibody, we quantified LTA4 hydrolase protein content in the cytosols of guinea pig tissues. The enzyme protein content correlated well with the enzyme activity with a correlation coefficient of 0.87. However, the enzyme activity per mg of the enzyme in the cytosols was low, particularly in the liver and adrenal gland, compared with the specific activity of the purified enzyme. These observations suggest the presence of inhibitory substances and/or inactive enzymes in the cytosols of these tissues. To determine the cellular localization of LTA4 hydrolase in tissues other than blood cells, we carried out immunohistochemical examinations of guinea pig tissues. We identified epithelial cells in the tracheobronchial system and gastrointestinal tract, smooth muscle cells in the bronchi and aorta, vascular endothelial cells, and the intestinal plexus as novel cellular sources of the enzyme in the parenchyme of the tissue. Thus, LTA4 hydrolase was widely distributed in various types of parenchymal cells in the tissues, and this observation warrants further investigations on the biological activities of LTB4 in these cells and tissues.

Animals↗

Serum concentration of soluble interleukin-2 receptor as a sensitive parameter of disease activity in sarcoidosis.

We investigated the clinical value of measuring serum concentrations of soluble IL-2R in monitoring sarcoidosis. Serum concentrations of soluble IL-2R were measured in 70 patients with sarcoidosis. The mean value for active untreated sarcoidosis was 1,143 +/- 509 U/ml, while the normal range in 97 healthy control subjects was 80 to 300 U/ml. The mean value for active untreated sarcoidosis was significantly higher than that for dormant disease (353 +/- 183 U/ml) or that for corticosteroid-treated patients (380 +/- 151 U/ml). Serial changes in serum soluble IL-2R level were studied in cases of spontaneous remission or in corticosteroid-treated patients; a good correlation was noted between the changes in serum level of soluble IL-2R and clinical status. A positive correlation was noted between serum concentration of soluble IL-2R and serum ACE activity. These data confirmed that measurement of serum concentration of soluble IL-2R could be used in monitoring the disease activity in sarcoidosis.

Adult↗

[Primary pulmonary lymphoma diagnosed by transbronchial biopsy and bronchoalveolar lavage findings].

A 45 year-old male was admitted to Tokyo University Hospital because of a submandibular tumor. Biopsy specimen of the tumor showed medium-sized non-Hodgkin's lymphoma of follicular type and immunoperoxidase staining of frozen sections demonstrated an overwhelming predominance of B lymphocytes with IgM, lambda chain. In the meanwhile, chest X-ray taken on admission showed an ill-defined consolidation with a tumor-like appearance in the right middle lung field. Transbronchial biopsy of this lesion revealed massive infiltrations of small and medium sized lymphocytes, having the same markers as those of submandibular tumor (IgM, lambda chain) and an analysis of bronchoalveolar lavage showed a significant increase of CD19-positive B lymphocytes. Reviewing of check-up X-ray films showed the lung lesion to have preceded the submandibular tumor and to have increased its size in several years. On the basis of the similarity of histological and immunohistochemical findings between pulmonary and submandibular tumor, and considering the time course of the appearance of these tumors, we concluded that these tumors were of the same histological nature and had originated in the lung and metastasized to submandibular gland. This is a relatively rare case of pulmonary lymphoma metastasizing to the submandibular gland, in which transbronchial biopsy specimen and analysis of lymphocytes in bronchoalveolar lavage were helpful in establishing the diagnosis.

Biopsy↗

Purification of human lung angiotensin-converting enzyme by high-performance liquid chromatography: properties and N-terminal amino acid sequence.

Angiotensin-converting enzyme from the human lung was purified to apparent homogeneity, using high-performance liquid chromatography following trypsin treatment of the detergent-extract. A 1,750-fold purification was achieved with a 26% yield. The specific activity of the enzyme was 105 units per mg protein with the substrate hippuryl-L-histidyl-L-leucine (HHL) at 37 degrees C, and the Km value for HHL was 1.9 mM. The molecular weight was estimated to be 170,000 by sodium dodecyl sulfate gel electrophoresis, and the isoelectric point was about 4.8, by chromatofocusing. The N-terminal amino acid sequence was (NH2)-X-X-Pro-Gly-Leu-Glu-Pro-Gly-X-Phe-Ser-Ala-Arg-Glu-Ala-Gly-Ala. This is highly homologous to the corresponding sequences of the enzymes from bovine and rabbit lung and from pig, bovine, and mouse kidney, but significantly different from that of the human kidney enzyme.

Amino Acid Sequence↗

Effects of smoking on the synthesis of leukotriene B4 by rat alveolar macrophages.

Leukotriene B4 (LTB4) is a potent chemotactic factor for polymorphonuclear leukocytes. It was reported recently that pulmonary macrophages from some mammalian species synthesize and release LTB4. Laviolette et al. reported the decrease of LTB4 synthesis in smokers' alveolar macrophages (AM). In this paper, we report the chronic effects of passive smoking on the production of LTB4 by rat AM. Some rats inhaled tobacco smoke and some inhaled smoke which did not contain nicotine. LTB4 production from AM from these rats was compared. In the tobacco-smoking group (n = 12), LTB4 production was 8.0 +/- 2.4 ng/10(6) cells. This value was significantly lower than in the nonsmoking (NS) group (n = 12; 16.5 +/- 4.5 ng/10(6) cells; p less than 0.01) and in the non-nicotinized cigarette smoking (NNCS) group (n = 8; 18.5 +/- 3.5 ng/10(6) cells; p less than 0.01). There were no significant differences between the NS and the NNCS group. These data may suggest that chronic inhalation of nicotine in tobacco smoke decreases LTB4 production activity of rat AM. The precise mechanism of decreased synthesis of LTB4 is not clear but it may have some immunological effects on the lung.

Animals↗

[An autopsy case of adenocarcinoma of the lung with signet ring cells, manifesting with aphasia and hemiparesis due to nonbacterial thrombotic endocarditis].

A 42-year-old male was admitted to Tokyo University Hospital because of confusion, aphasia and right hemiparesis. Cranial computed tomography and cerebral angiography demonstrated cerebral infarction due to occlusion of the left middle cerebral artery, while chest roentgenography disclosed a nodular shadow in the right upper lobe and swelling of right hilar and paratracheal lymph nodes. These findings suggested carcinoma of pulmonary origin and tumor-associated cerebral thrombosis, but a possibility of gastric cancer was raised by the finding of cervical lymph node biopsy which revealed signet ring cells in metastatic adenocarcinoma. He developed disseminated intravascular coagulation syndrome and died on the 83rd hospital day. Autopsy revealed adenocarcinoma of the lung with signet ring cells and non-bacterial thrombotic endocarditis which appeared to be responsible for the cerebral infarction. The relationship between adenocarcinoma of the lung with signet ring cells and non-bacterial thrombotic endocarditis was discussed.

Adenocarcinoma↗

Measurement of angiotensin-converting enzyme activity in intact human alveolar macrophages and effect of smoking.

Serum angiotensin-converting enzyme (ACE) activity is known to be elevated in various granulomatous conditions such as sarcoidosis, whose characteristic epithelioid cells are thought to belong to the macrophage series. It was recently shown that alveolar macrophages had ACE activity in their sonicated and homogenate forms. We investigated ACE activity of human alveolar macrophages in the intact form using a sensitive radioimmunoassay of generated angiotensin II. We also investigated the effect of smoking on ACE activity of alveolar macrophages using this method. Alveolar macrophages generated angiotensin II (218 +/- 106 pg/20 min/10(5) cells). More angiotensin II was generated in smokers (246 +/- 119 pg/20 min/10(5) cells) than in nonsmokers (160 +/- 50 pg/20 min/10(5) cells) (p less than 0.05). These data showed that ACE activity of macrophages is higher in smokers than nonsmokers.

Angiotensin I↗