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Biomedical subjects

Y Fukuchi

Publications and source records attributed to Y Fukuchi.

At least 91 records · Page 5Linked to original sources
PubMed1999

[A case of elderly onset sarcoidosis].

Although sarcoidosis is generally considered a disease of young and middle aged adults, there have been a certain number of cases among elderly. However it is unknown whether sarcoidosis in the elderly is recurrence of prior disease or initial onset at old ages. We present a 77-year-old woman with sarcoidosis the onset of which was considered to be in the last 6 months prior to the initial diagnosis. The patient was admitted to our hospital for further evaluation of bilateral hilar and mediastinal lymphadenopathy (BHL) and uveitis. BHL was not present in a chest radiograph taken 6 months prior to the admission. A clinical diagnosis of sarcoidosis was made by elevated serum angiotensin converting enzyme (ACE) and lysozyme (24.9 IU/L and 18.2 micrograms/ml, respectively), negative tuberculin skin test, concomitant presence of uveitis, and a high proportion of lymphocytes (33.2%) in bronchoalveolar lavage fluid with an elevated CD4/CD8 ratio (24.5). This is a noteworthy case of sarcoidosis in which we could confirm elderly onset of the disease.

Age of Onset↗
PubMed1999

Cytotoxic activity and cytokine gene induction of Asp-hemolysin to murine macrophages.

We examined the effects of Asp-hemolysin from Aspergillus fumigatus Fresenius-Muramatsu strain on the viability and cytokine gene expression of mouse peritoneal macrophages. The cytotoxic activity of Asp-hemolysin to macrophages cultured in FCS-RPMI medium was increased in a dose-dependent manner. Treatment of Asp-hemolysin with N-ethylmaleimide or sulfo-N-hydroxy-sulfosuccinimide-acetate caused a remarkable loss of the cytotoxic activity, however, the cytotoxic activity of Asp-hemolysin to macrophages cultured in serum-free medium was significantly increased as compared with that in FCS-RPMI medium. As other biological activities of Asp-hemolysin, tumor necrosis factor-alfa (TNF-alfa), interleukin-1 beta(IL-l beta) and interleukin-1 alfa (IL-l alfa) mRNA expression were observed in macrophages cultured with 1 micro g/ml of Asp-hemolysin.

Animals↗
PubMed1999

A novel retinoic acid-resistant acute promyelocytic leukemia model in vitro and in vivo (review).

Differentiation-inducing therapy by all-trans retinoic acid (RA) is now a standard therapy in patients with acute promyelocytic leukemia (APL). Nearly all patients achieve complete remission by the treatment of all-trans RA, however, clinical remissions are usually of brief duration, and these patients often develop RA-resistant disease. The mechanisms of RA-resistance in APL cells are poorly understood and most clinical approaches have not been successful in overcoming RA-resistance. We have recently established a novel APL cell line (UF-1) with RA-resistant features. In addition, we have established human GM-CSF-producing transgenic (hGMTg) SCID mice system. UF-1 cells were inoculated either intraperitoneally or subcutaneously into hGMTg SCID mice and made the first RA-resistant murine APL model. These RA-resistant APL model systems in vitro and in vivo may be useful for investigating the molecular studies on the block of leukemic cell differentiation and as means to investigate the mechanisms of RA-resistance. Moreover, this murine model system will be important for developing novel therapeutic strategies in RA-resistant APL.

Animals↗
PubMed1999

[Intralobar pulmonary sequestration presenting increased serum CEA, CA 19-9, and CA 125, and associated with asymptomatic pulmonary aspergillosis].

A 44-year-old woman was admitted to our hospital for further evaluation of a consolidated shadow in the left lower lobe and the evaluation of serum tumor markers (CEA 46.3 ng/ml, CA 19-9 1911 U/ml, and CA 125 103 U/ml). Chest computed tomography revealed an irregular shaped, low density mass shadow in the left S10 region, suggesting the diagnosis of pulmonary sequestration or bronchial atresia. However digital subtraction angiography failed to demonstrate an anomalous feeding artery. We could not rule out the possibility that a malignant lesion was included in the consolidated shadow. A left thoracotomy revealed an intralobar pulmonary sequestration of the left lower lobe. Hyphae of aspergillus were found in the lumen of the cystic bronchus of the resected lung. Immunohistochemical studies showed strong expression of CEA, CA 19-9, and CA 125 by bronchial epithelia in the pulmonary sequenstration. The serum values of tumor markers returned to their normal ranges after surgery.

Adult↗
PubMed1999

[The simple swallowing provocation test as a means of screening for swallowing disorders: a comparison with the water swallowing test].

The sensitivity and specificity of the simple swallowing provocation test (S-SPT) were evaluated in a group of patients who were being examined for aspiration pneumonia (ASP) (ASP group: 72.5 +/- 3.9 years old) and in a group of age-matched control subjects (CTRL group: 69.5 +/- 2.9 years old). The S-SPT was evaluated in terms of the swallowing response and latent time (LT) for swallowing after a bolus injection of 0.4 ml of distilled water at the suprapharynx. Responses to the S-SPT were classified as normal or abnormal, dependent on induction of the swallowing reflex within 3 seconds after bolus injection. The sensitivity and specificity of the S-SPT in detecting ASP were calculated. Of the 40 patients in the ASP group, 18 were given a diagnosis of ASP on the basis of clinical findings and laboratory examinations. The sensitivity and specificity of the S-SPT were 94.4% and 86.4%, respectively, compared to 77.8% and 68.1%, respectively, for the water swallowing test. Because the S-SPT can be performed without any need for special patient effort or cooperation, it should be effective in diagnosing ASP in a wide variety of patients, including those who are bedridden.

Aged↗
PubMed1998

Oxidized low density lipoprotein inhibits the hemolytic activity of Asp-hemolysin from Aspergillus fumigatus.

We have examined the effect of chemically modified human low density lipoproteins (LDLs), acetylated LDL and oxidized LDL, on the hemolytic activity of Asp-hemolysin. Oxidized LDL, but not acetylated LDL, inhibited the hemolytic activity of this toxin. The inhibitory effects of oxidized LDL increased with the time of Cu(2+)-induced LDL oxidation. Similar inhibition was observed in the filtrate which was separated from the incubation mixture of Asp-hemolysin with oxidized LDL (for 2 h of oxidation) following ultrafiltration through a membrane with a molecular mass cutoff of 100,000. However, at longer LDL oxidation times, the inhibition by the filtrates was less than the control mixture without ultrafiltration. We suggest that the inhibition by oxidized LDL was due to the binding of oxidized LDL to Asp-hemolysin at shorter LDL oxidation times.

Acetylation↗
PubMed1998

Induction of DNA fragmentation and HSP72 immunoreactivity by adenovirus-mediated gene transfer in normal gerbil hippocampus and ventricle.

Foreign genes have been successfully transferred and expressed in experimental animal brains using adenoviral vectors. However, it is not fully understood whether adenovirus-mediated gene transfer causes stressful or cytotoxic injury in brain. A replication-defective adenoviral vector containing the Escherichia coli lacZ gene (AdCMVnLacZ) was directly injected into right hippocampus and lateral ventricle of normal gerbil brains. Temporal and spatial profiles of the expression of lacZ gene products, DNA fragmentation detected by terminal deoxynucleotidyl d-UTP nick end labeling (TUNEL) staining, and heat shock protein 72 (HSP72) immunoreactivity were examined until 21 days after the injection. In the ventricle, lacZ gene was immediately and strongly expressed at 8 hr after the injection of AdCMVnLacZ, with a peak at 1-3 days, and disappeared by 21 days. Although a small number of choroid plexus cells were TUNEL positive at 3 and 7 days, no HSP72 immunostaining was observed in the ventricle. Small-to-moderate expression of lacZ gene was found in the needle route from 8 hr to 3 days after the injection, and a small number of TUNEL-positive cells were detected at the needle track at 1-3 days. In the hippocampus, lacZ gene was markedly expressed around the dentate gyrus (DG) at 8 hr to 3 days with a peak at 1 day. Large number of TUNEL or moderate-to-dense HSP70 staining cells were also detected in the same area. CA1 neuronal cells just adjacent to the needle route showed TUNEL positivity at 1 to 3 days. However, the TUNEL staining was not associated with lacZ gene expression. The majority of lacZ-expressing cells were discriminated from the TUNEL-positive cells, whereas some were double-positive with HSP72 staining in DG. Cellular loss was observed in the CA1 layer around the needle route. An apoptotic change was morphologically observed in the marginal region of the DG at 1-3 days and in the ventricle at 3-7 days. In the sham control group, TUNEL-positive or HSP72-staining cells were only detected around the needle track including CA1 cells adjacent to the needle route. These data suggest that adenoviral gene transfer may induce direct traumatic injury in the CA1 sector near the needle route, indirect apoptotic cell loss in the DG and ventricle, and stressful effect on the dentate granule cells in association with adenovirus infection in normal gerbil brain.

Adenoviridae↗
PubMed1998

Impaired anaphylactic responses with intact sensitivity to endotoxin in mice lacking a platelet-activating factor receptor.

Platelet-activating factor (PAF) is a potent phospholipid mediator with diverse biological activities in addition to its well-known ability to stimulate platelet aggregation. Pharmacologic studies had suggested a role for PAF in pregnancy, neuronal cell migration, anaphylaxis, and endotoxic shock. Here we show that disruption of the PAF receptor gene in mice caused a marked reduction in systemic anaphylactic symptoms. Unexpectedly, however, the PAF receptor-deficient mice developed normally, were fertile, and remained sensitive to bacterial endotoxin. These mutant mice clearly show that PAF plays a dominant role in eliciting anaphylaxis, but that it is not essential for reproduction, brain development, or endotoxic shock.

Anaphylaxis↗
PubMed1998

Evaluation by ventilation and perfusion scintigraphy in patients who developed postural hypoxemia in the supine position.

Ventilation and pulmonary perfusion scintigraphy were performed in 7 patients in whom postural change from the sitting position to the supine position decreased partial oxygen pressure in arteries (PaO2) by 15 mmHg or more. Six of these 7 patients were obese. Five patients had organic pulmonary disease or space occupying lesions of the liver. On lateral supine-position images taken by using the continuous inhalation method for 81mKr ventilation scintigraphy, ventilation was reduced in the dorsal area corresponding to a gravity-dependent area, but on pulmonary perfusion scintigrams, there were no marked changes compared to normal adults. The mismatch of ventilation to perfusion may have caused hypoxemia. Reduced ventilation was correlated with reduced PaO2. The distribution of 81mKr bolus gas inhalation suggested closure of the airway in the dorsal area at functional residual capacity (FRC), which means the resting expiratory level, in the supine position.

Adult↗
PubMed1998

Cytokine dependent growth of human TF-1 leukemic cell line in human GM-CSF and IL-3 producing transgenic SCID mice.

Although severe combined immunodeficient (SCID) mice are considered useful as an animal model for human hematopoietic diseases, the complete reconstruction of human hematopoietic cells can not be established even in these mice. This appears to be because human cytokines, adhesion molecules and extracellular matrices which support differentiation and growth of human hematopoietic cells differ from those in animals. To improve this animal model, we attempted to produce transgenic (Tg) mice producing human interleukin 3 (hIL-3) and human granulocyte macrophage colony stimulating factor (hGM-CSF) with the homozygote of the scid gene. We established two Tg mouse lines, one releasing both 0.5-1 ng/ml of hIL-3 and 0.05-0.2 ng/ml of hGM-CSF in their sera and another releasing only high (2-10 ng/ml) levels of hGM-CSF. When human cytokine-dependent myeloid cell line, TF-1, was subcutaneously transplanted into these two Tg-SCID mouse lines, TF-1 could be successfully engrafted and grew in all lines of Tg-SCID mice but not in control mice. We also observed that TF-1 grows in GM-CSF Tg-SCID mice in a dose dependent manner in vivo and IL-3 shows an additive effect on its growth. These results indicated that these Tg-SCID mice were an useful in vivo model for investigating human leukemogenesis, especially the role of IL-3 and GM-CSF in leukemogenesis.

Animals↗
PubMed1998

Growth stimulation of non-small cell lung cancer xenografts by granulocyte-macrophage colony-stimulating factor (GM-CSF).

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been suggested to be involved in the carcinogenesis of some types of tumours by autocrine or paracrine mechanisms. We examined GM-CSF/GM-CSF receptor (GM-CSFR) gene expression in 20 human non-small cell lung cancer (NSCLC) xenografts. The stimulatory effects of GM-CSF were examined using GM-CSF transgenic severe combined immunodeficient (SCID) mice (GM-Tg-SCID), which produce abundant human GM-CSF. A NSCLC xenograft (LC11-JCK), expressed GM-CSFR but not GM-CSF, and showed more rapid growth in GM-Tg-SCID than non-GM-CSF transgenic SCID mice (non-Tg-SCID). GM-CSF gene expression was detected in 48 of 90 (53%) primary NSCLC human specimens and GM-CSFR gene expression was detected in 42 specimens (47%). GM-CSF expression was detected in 13 of 30 squamous cell carcinoma specimens (43%) and GM-CSFR expression was detected in 10 specimens (33%). Patients with squamous cell carcinoma coexpressing GM-CSF and GM-CSFR showed significantly poorer prognosis than those expressing neither GM-CSF nor GM-CSFR (P < 0.05, Cox-Mantel test). These results suggest that GM-CSF can have a stimulatory effect on some NSCLC.

Animals↗
PubMed1998

DNA fragmentation and HSP72 gene expression by adenovirus-mediated gene transfer in postischemic gerbil hippocampus and ventricle.

A replication defective adenoviral vector containing the E. coli lacZ gene (AdCMVnLacZ) was directly injected into right hippocampus and lateral ventricle immediately after 5 min of transient global ischemia in gerbils. The relations between the lacZ gene expression and DNA fragmentation or heat shock protein 72 (HSP72) immunoreactivity were examined up to 21 days post ischemia. The lacZ gene was transiently expressed at 1 day in the hippocampus except around the CA1 region, while a large number of the periventricular cells strongly expressed the lacZ gene from 8 h to 7 days. In CA1 layer, terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) positive cells, which were present only adjacent to the needle track at 8 h to 1 day, became more extensive in the whole CA1 layer at 3 to 7 days. TUNEL-positive cells were also detected around the DG at 1 day, around the needle track at 8 h to 3 days, and in the choroid plexus cells at 7 days. HSP72 staining was detected in the subiculum at 1 to 3 days, the dentate granule cells at 8 h to 1 day, and in the CA3 or CA4 pyramidal cells at 1 to 3 days. Some lacZ expressing cells were double-positive with HSP72 in DG, while the majority of those were distinguished from the TUNEL-positive cells. Pyramidal neurons were almost completely lost in the CA1 sector at 7 days after the ischemia. The present study demonstrates the successful LacZ gene transfer into the hippocampus and ventricle of postischemic gerbil brain except in the vulnerable CA1 layer by adenoviral vector injection. However, adenovirus-mediated gene transfer may induce indirect apoptotic cell death in the DG and ventricle, in addition to direct traumatic injury around the needle track.

Adenoviridae↗
PubMed1998

Establishment of a retinoic acid-resistant human acute promyelocytic leukaemia (APL) model in human granulocyte-macrophage colony-stimulating factor (hGM-CSF) transgenic severe combined immunodeficiency (SCID) mice.

To understand the mechanisms and identify novel approaches to overcoming retinoic acid (RA) resistance in acute promyelocytic leukaemia (APL), we established the first human RA-resistant APL model in severe combined immunodeficiency (SCID) mice. UF-1 cells, an RA-resistant APL cell line established in our laboratory, were transplanted into human granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing SCID (hGMTg SCID) mice and inoculated cells formed subcutaneous tumours in all hGMTg SCID mice, but not in the non-transgenic control SCID mice. Single-cell suspensions (UF-1/GMTg SCID cells) were similar in morphological, immunological, cytogenetic and molecular genetic features to parental UF-1 cells. All-trans RA did not change the morphological features of cells or their expression of CD11b. RA did not alter the growth curve of cells as determined by MTT assay, suggesting that UF-1/GMTg SCID cells are resistant to RA. These results demonstrate that this is the first RA-resistant APL animal model that may be useful for investigating the biology of this myeloid leukaemia in vivo, as well as for evaluating novel therapeutic approaches including patients with RA-resistant APL.

Animals↗
PubMed1998

The carboxyl-terminal fragment of osteopontin suppresses arginine-glycine-asparatic acid-dependent cell adhesion.

Osteopontin (OPN) is a secreted glycoprotein implicated in cell adhesion. It contains the arginine-glycine-asparatic acid (RGD) cell adhesive domain and the thrombin cleavage sequence. Although thrombin cleavage of OPN has been shown to be of physiological importance, the function of C-terminal OPN fragment cleaved by thrombin remains unknown. To determine its role, we performed cell adhesion assays using glutathione S-transferase-OPN fusion protein fragments and full-length OPN fusion protein. The N-terminal fragment containing RGD motif promoted enhanced adhesion of mouse and human fibroblasts by 2.9 and 2.8 folds in comparison with full-length OPN, respectively. The enhanced adhesion of both cells mediated by N-terminal fragment was significantly suppressed by addition of C-terminal fragment lacking RGD motif that has less cell adhesive property than full-length OPN. These results suggest that the C-terminal domain may play a pivotal role in regulating OPN functions by suppressing the RGD-dependent cell adhesion.

3T3 Cells↗
PubMed1998

Airway hyperresponsiveness to methacholine in mutant mice deficient in endothelin-1.

Endothelin-1 (ET-1) has recently been reported to have a potential pathophysiologic role in bronchial asthma. In the current study, we hypothesized whether ET-1 and a gene encoding ET-1 might be involved in airway hyperresponsiveness (AHR), which is a major feature of bronchial asthma. To test this hypothesis, we investigated airway responsiveness in ET-1(+/-) heterozygous knockout mice, which genetically produce lower levels of ET-1, and in ET-1(+/+) wild-type mice. Airway responsiveness was assessed through the concentration of an agonist required to double lung resistance (EC200 RL). Unexpectedly, airway responsiveness to methacholine was markedly enhanced in ET-1(+/-) heterozygous mice as compared with ET-1(+/+) wild-type mice (EC200 RL: 1.8 +/- 0.1 versus 21.6 +/- 5.6 mg/ml, p < 0.002). Pretreatment with the nitric oxide (NO) synthase inhibitor Ng-monomethyl-L-arginine (L-NMMA) significantly enhanced methacholine responsiveness in ET-1(+/+) wild-type mice, but not in ET-1(+/-) heterozygous mice. Meanwhile, there was no difference between ET-1(+/-) heterozygous mice and the wild-type mice in airway responsiveness to 5-hydroxytryptamine (5-HT). In sensitized mice, no significant differences in responsiveness to antigen were observed between the two groups. These findings suggest that the gene encoding ET-1 may be potentially involved in the etiology of airway hyperreactivity, and that the decrease in ET-1 concentration is associated with AHR to methacholine. In mice, ET-1 as well as NO may have a significant role in the homeostasis of airway physiology.

Airway Resistance↗
PubMed1998

Investigation of effects of anesthesia and age on aspiration in mice through LacZ gene transfer by recombinant E1-deleted adenovirus vectors.

To examine the role of disturbed upper airway reflexes in aspiration, we administered 20 microliters of the adenovirus (Ad) vector Ad-CMV-LacZ or 20 microliters of phosphate buffered saline (PBS) intranasally to C57 black mice. We investigated expression of the LacZ gene by this Ad vector in the nostrils of each mouse, with or without anesthesia. Under anesthesia, LacZ gene expression was detected in the lungs of every mouse given the Ad vector. However, no LacZ gene expression was found in the trachea or lungs of mice given the Ad vector without anesthesia. In mice given PBS or wild-type adenovirus transnasally during anesthesia, there was no LacZ gene expression in the nostrils, trachea, or lungs, suggesting that with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining, blue-stained cells indicated transferred LacZ gene expression. These results suggested that aspiration of intranasal solution into lower airways was caused by disturbed upper airway reflexes during anesthesia. This process can be analyzed by the distribution of LacZ gene expression in airways. We next examined the effect of age on anesthesia-induced aspiration. Twenty-six-mo-old mice exhibited more LacZ gene expression in their lungs than did 6-mo-old mice at a concentration of 0.5 to 4.0% halothane in 100% oxygen. This suggests that light anesthesia may depress upper airway reflexes and cause aspiration in older animals. This novel model of aspiration, generated with the Ad-CMV-LacZ vector, may be useful for elucidating the mechanism of development of aspiration pneumonia in relation to age-related impairment of upper airway reflexes.

Adenoviridae↗