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Biomedical subjects

H Yotsumoto

Publications and source records attributed to H Yotsumoto.

At least 19 recordsLinked to original sources
PubMed1991

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↗
PubMed1991

[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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

[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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

[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↗
PubMed1988

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↗
PubMed1987

Leukotriene A4 hydrolase in the human lung. Inactivation of the enzyme with leukotriene A4 isomers.

Leukotriene A4 hydrolase from the human lung was purified to apparent homogeneity. The molecular weight (68,000-71,000), the amino acid composition, and the N-terminal amino acid sequence were similar to those of the human neutrophil enzyme but different from those of human erythrocyte enzyme. The lung enzyme was inactivated by its substrate, leukotriene A4. To elucidate the substrate and the inactivator specificity of this enzyme, we synthesized various geometric and positional isomers of leukotriene A4. 14,15-Leukotriene A4, leukotriene A4 methyl ester, and geometric isomers of leukotriene A4 could not serve as substrates, but they inactivated the enzyme. On the other hand, styrene oxide and (5S)-trans-5,6-oxide-8,10,14-cis-12-trans-eicosatetraenoic acid neither served as substrates nor inactivated the enzyme. These results indicate that whereas allylic epoxide structures of arachidonic acids are responsible for inactivation of the enzyme, the free carboxylic acid, 5,6-oxide, and the tetraene structure with the 7,9-trans-11,14-cis configuration are required as a substrate for leukotriene A4 hydrolase.

Arachidonic Acids↗
PubMed1987

Familial hyper-angiotensin converting enzyme (ACE)-emia: increased production of ACE by monocyte-macrophage.

We report here a familial clustering of elevated serum angiotensin converting enzyme (ACE) levels. The patient was a 58-year-old Japanese female. She had been in excellent health until the age of 45, when she noticed a decrease in visual acuity of her left eye. Despite intensive therapy under the diagnosis of occulusion of the central retinal vein, she lost her visual acuity at the age of 45. Thereafter, she has been in excellent health. The only abnormality found in this case has been a markedly elevated level of serum ACE (625 n mol/min/ml; normal range; 22-40 n mol/min/ml of serum). Her blood pressure was within normal limits (140/80 mmHg). There was no evidence for the diagnosis of sarcoidosis, Gaucher's disease, leprosy, hyperthyroidism, diabetic retinopathy, or liver disease. One of her two sisters also showed a marked increase in serum ACE activity (303 n mol/min/ml), and remarkably high levels of serum ACE (276 and 294 n mol/min/ml) were demonstrated in both of two sons of this sister. All the members of this family have been in excellent health. The serum ACE activity was activated by chloride and cobalt ions, and inhibited by EDTA, captopril and rabbit antiserum to purified human plasma ACE. Thus, our study showed a familial clustering of "hyper-ACE-emia", and the disorder appears to have been inherited as an autosomal dominant trait.

Cells, Cultured↗
PubMed1987

Primary pulmonary lymphoma demonstration of monoclonality by lymphocyte surface marker study.

We present here a case of small lymphocytic B cell lymphoma of the lung which developed in a 51-year-old Japanese man who was asymptomatic while his chest X-rays revealed slowly progressive infiltrative shadows. Findings of transbronchial lung biopsy suggested lymphoproliferative disorders and the diagnosis of B-cell lymphoma of the lung was established with lung specimen obtained by an open lung biopsy and through demonstration of monoclonal surface markers on lymphocytes in fresh frozen lung sections. Diagnostic value of surface marker analysis is emphasized.

Antibodies, Monoclonal↗