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Biomedical subjects

G Yamada

Publications and source records attributed to G Yamada.

At least 55 records · Page 3Linked to original sources

Nasal and pharyngeal abnormalities caused by the mouse goosecoid gene mutation.

The Goosecoid (gsc) gene is a homeobox-containing gene expressed first in the gastrula, and later during organogenesis in development. The gsc gene transcript is found in the first and second branchial arches, frontonasal mass in its late phase of expression. We have previously shown that targeted mutation of the mouse gsc gene leads to neonatal death and craniofacial defects. In this study, we performed histological studies on craniofacial phenotypes in order to elucidate the processes underlying the neonatal death of gsc mutant mice. We found that gsc mutant mice have aplastic nasal cavities and lack the Sinus Paranasalis. We also showed that secretory olfactory glands in the basal layers are aplastic. This is suggested to be essential defects for olfaction. gsc mutant mice also show several pharyngeal phenotypes, including defects in the pharyngeal muscles and the pharyngeal mucosa. It is therefore suggested that mutant mice develop lethal gastro-intestinal phenotypes caused by defects in breathing and sucking of milk as a consequence of these craniofacial disorders. These results should help elucidating the molecular genetic programs essential to the neonatal development of mammals.

Animals↗

Role of endothelin-1 in astrocyte responses after acute brain damage.

We examined the possibility of the involvement of endothelin (ET)-1, a potent vasoactive peptide, in the process of astrocyte proliferation after brain injury. Acute brain damage in rats was induced by cold-injury. Astrocytes changed from a differentiated state to an immature, RC-1-positive state immediately after the injury. In the injured site, the level of ET-1-like immunoreactivity in the tissue was significantly increased on the first postoperative day and was sustained at a high level for 5 days. ET(B) receptor mRNA was markedly but transiently down-regulated only on the first day after the injury. Brain extracts (BE) were prepared from the injured tissues, and their effects on the proliferative characteristics of astrocytes were examined in primary culture of astrocytes. The flat morphology, which was observed in association with cell proliferation, and DNA synthesis of astrocytes were enhanced by treatment with each of the BE from 1 (D1-BE), 3 and 5 days after the injury. A monoclonal antibody that recognizes the C-terminus of rat ET-1 and ET-3 inhibited the DNA synthesis of astrocytes induced by D1-BE. These results provide experimental evidence that ET-1 may participate in the initiation of gliosis in the acute phase of brain damage.

Acute Disease↗

Trace element composition and histological analysis of rat bones from the space shuttle.

The physiological and pharmacobiological changes associated with space flight are of greater concern. Exposure to a weightless environment has been shown to have numerous effects on body composition and organ functions. Alterations include decreases in muscle and liver mass, changes in bone structure and integrity, and changes in cardiovascular functions. Zero-gravity in particular has been reported to inhibit several physiological processes of bone formation, retard bone growth and impair the mechanical properties of bones. This report examines the effect of 14 days of spaceflight on the bone trace element compositions of rapidly growing rats. Marked changes of bone trace element contents were found in either weight-bearing bones or non-weight-bearing bones, depending on the metal species. Histological examination revealed an irregular thickening of the endosteal surface of the cortical bone (thoracic vertebrae) of the in-flight rat, whereas it was uniform in the ground control. We suggest that the microgravity environment causes several bone alternations, such as abnormal trace element compositions and defects in vertebral maturation.

Animals↗

[Thymic carcinoma associated with pulmonary sarcoidosis].

A 54-year-old man who worked as a farmer was admitted to the hospital in August 1989 because of bilateral hilar adenopathy that was detected during a mass screening. Laboratory examination showed a high serum lysozyme level and the PPD skin test was negative. Examination of a specimen obtained by transbronchial lung biopsy revealed non-caseous epithelioid cell granuloma. Sarcoidosis was diagnosed. The patient was not treated, and the bilateral hilar adenopathy had lessened by 1992. The patient was readmitted to our hospital because of right hilar and upper mediastinal enlargement seen on a chest radiograph in April 1994. Computed tomography and magnet resonance imaging disclosed an anterior mediastinal tumor in contact with the right upper lobe, the left inominate vein, and the pericardium. Bronchoscopy showed no abnormality in the right upper-lobe bronchus. Examination of a specimen obtained from the B3b bronchus showed no evidence of malignant cells. Examination of a tumor specimen obtained by transdermal biopsy showed squamous cell carcinoma. After the patient underwent combination chemotherapy, the tumor ws resected, along with the right upper lobe, the left inominate vein, and the pericardium, which were difficult to separate from the tumor. Postoperative pathological examination showed that squamous cell carcinoma was intermingled with normal thymus tissue. We believe that squamous cell carcinoma originated in the thymus. Non-caseous epithelioid cell granulomas were also found in the resected right upper lobe and in a mediastinal lymph node. The patient was discharged after post-operative irradiation of the mediastinum. Thymic carcinoma is rare, and sarcoidosis in a patient with thymic carcinoma is very rare. T lymphocytes are very important in the pathogenesis of sarcoidosis, and the thymus is involved in the growth and differentiation of T lymphocytes. The occurrence of these two diseases in one patient is interesting, but the relationship is not clear.

Carcinoma, Squamous Cell↗

Differential accumulation of calcium and phosphorus in aged human arteries.

To elucidate age-related changes of human arteries, relative contents (RCs) of minerals were analyzed by inductively coupled plasma atomic emission spectrometry on the thoracic aorta, basilar, coronary, femoral, and radial arteries from 27 subjects within the age range between 0 and 92 years old (Ys). Calcium and phosphorus never accumulated uniformly in any of the arteries such as the thoracic aorta, basilar, coronary, femoral, and radial arteries. The accumulations of calcium and phosphorus occurred earlier in the order of the femoral artery, thoracic aorta, coronary artery, and basilar or radial artery.

Adolescent↗

Th1/Th2 response profiles to the major allergens Cry j 1 and Cry j 2 of Japanese cedar pollen.

Cry j 1 and Cry j 2 are known to be the major allergens of Japanese cedar pollen. A comparative study was carried out on the immune responses to stimulation with Cry j 1 and Cry j 2 in 24 symptomatic patients and six nonallergic subjects. In T-cell proliferation assays, mean stimulation indexes (SI) were 10.6 for Cry j 1 and 11.7 for Cry j 2 stimulation, respectively, in the allergic patients. Two of the nonallergic subjects showed strong T-cell proliferation to both allergens, while the remainder did not. All the allergic subjects (17/17) showed high titers of anti-Cry j 1 IgE antibody at a mean value of 165 U/ml, whereas only 64% responded to Cry j 2 with low titers at a mean value of 26 U/ml. Nonallergic subjects did not respond with IgE production. Allergic subjects were further examined for their cytokine production profiles. All allergic subjects tested (16/16) produced high levels of interferon-gamma (IFN-gamma) in response to Cry j 1 with a mean value of 918 pg/ml, while only five subjects showed significant elevation of IFN-gamma production in response to Cry j 2 with a mean value of 679 pg/ml. The remainder produced small amounts of IFN-gamma. Cry j 1 induced higher levels of interleukin (IL)-10 gene expression than did Cry j 2 stimulation, while both allergens induced IL-4 expression at a similar level. The IL-12 p35 gene was constitutively expressed, whereas the IL-12 p40 gene expression in Cry j 1-stimulated cells was elevated eightfold over that of nonstimulated cells. Increased expression of the IL-12 p40 gene was negligible in Cry j 2-stimulated cells. Thus, Cry j 1 stimulated mixed features of Th1 and Th2-like responses, while Cry j 2 played a minor role in inducing IgE production and cytokine (IFN-gamma, IL-10, and IL-12) production, except for IL-2 production and strong T-cell proliferative activity. Therefore, it was concluded that Cry j 1 is the more important allergen, and that T-cell proliferation assays do not necessarily reflect the level of allergenicity.

Allergens↗

Immunodominance of seven regions of a major allergen, Cry j 2, of Japanese cedar pollen for T-cell immunity.

The immunodominant regions of the Japanese cedar pollen allergen Cry j 2 for T-cell immunity were determined with whole peripheral blood lymphocytes (PBL) derived from seven allergic patients and three nonallergic subjects. Cry j 2-stimulated T-cell proliferation was inhibited by anti-HLA-DR, but not by anti-HLA-DQ antibody, indicating that the responding T cells recognized the allergen peptides associated with HLA-DR molecules. It was found that seven regions of Cry j 2, i.e., regions corresponding to amino acid numbers 1-26, 70-84, 151-167, 187-203, 252-279, 283-314, and 345-362, were immunodominant for T-cell proliferation. Thus, Cry j 2 bears a limited number of immunodominant regions despite polymorphic features of HLA-DR in the immune system. This suggests the possibility of molecularly designing Cry j 2 antagonists that could downregulate allergic reactions to Japanese cedar pollen.

Case-Control Studies↗

Comparison of adhesion molecule expression on light and normal-density eosinophils from patients with eosinophilia.

Increased numbers of light-density eosinophils (LDEs) are observed in the blood of patients with eosinophilia and are associated with disease activity. LDEs are thought to be metabolically more activate than normal-density eosinophils (NDEs). Recent studies suggest that cytokine-induced eosinophil activation is associated with adhesion molecule expression. The activated state of LDEs may result from increased expression of adhesion molecules. This study compared the expression of eosinophil adhesion molecules on LDEs and NDEs from various diseases characterized by eosinophilia. Expression of very late antigen-4 (VLA-4), lymphocyte function-associated antigen-I (LFA-1) and macrophage antigen-1 (Mac-1) on eosinophils from patients with eosinophilia was increased compared with those from healthy subjects. Mac-1 expression on LDEs was higher than on NDEs. These results suggest that VLA-4 plays a role in selective migration of eosinophils into the inflammatory tissue, and that Mac-1 is associated with activation of eosinophils in eosinophilic diseases.

Cell Adhesion Molecules↗

[Pulmonary arteriovenous fistula--usefulness of three-dimensional computed tomography].

A 57-year-old woman was admitted to our hospital for examination of an abnormal shadow in the left middle lung field. The lesion was in S4 of the left upper lobe, with dilation of A5 b and V5 b, and was suspected to be a pulmonary arteriovenous fistula. A three dimensional CT scan showed a tortuous and irregularly dilated vessel. Color doppler imaging showed a mosaic pattern of blood flow. These findings indicated that the fistula was attached to the pleura. The patient underwent thoracoscopic partial resection of the lung.

Arteriovenous Fistula↗

Activin A inhibits Pax-6 expression and perturbs cell differentiation in the developing spinal cord in vitro.

We have developed an in vitro model of the isolated chicken neural plate. Here we demonstrate that even in the absence of notochord, the neural plate rapidly develops a typical dorsoventral patterning. This observation suggests that the ventral cell types are specified or at least predetermined prior to notochord formation and that permissive conditions are sufficient for differentiation of ventral structures. Treatment of the neural plate with activin A extinguishes Pax-6 gene expression, whereas the dorsal markers Pax-3 and Pax-7 are still expressed. The absence of Pax-6 transcripts can be correlated with an impeded differentiation of the motor neurons, whereas the floor plate seems to be enlarged. We propose that the region-specific expression of Pax-6 in the spinal cord is under the control of activin-like molecules.

Activins↗

Virion-like structures in HeLa G cells transfected with the full-length sequence of the hepatitis C virus genome.

BACKGROUND & AIMS: The process and the site of hepatitis C virus (HCV) particle formation in cells after infection remain unknown. The aim of this study was to create an in vitro model for the study of HCV particle formation. METHODS: HeLa G cells were transfected with the full-length sequence of the HCV genome. Viral protein expression was analyzed using immunoblotting. The cells were examined using immunoelectron and conventional electron microscopy. RESULTS: Core, E2, NS3, NS5a, and NS5b proteins were identified using immunoblotting. Immunoelectron microscopy showed that the core antigen was located along the membrane of the endoplasmic reticulum (ER) and occasionally in its cisternae. Core antigen-positive particles of 30 nm in diameter were found in the cytosol and in the cisternae of the ER. The particles in the cisternae were coated with an outer membrane that was connected to the ER membrane. Conventional electron microscopy revealed particles of 45 nm in diameter with electron-dense cores in the cisternae of the ER. The outer membrane of the particles was occasionally connected to the ER membrane. CONCLUSIONS: The findings suggest that HCV core proteins are synthesized and assembled into particles in the cytosol and that they bud into the cisternae of the ER to form coated particles.

Base Sequence↗

Targeted mutation of the murine goosecoid gene results in craniofacial defects and neonatal death.

The goosecoid gene encodes a homeodomain-containing protein that has been identified in a number of species and has been implicated in a variety of key developmental processes. Initially suggested to be involved in organizing the embryo during early development, goosecoid has since been demonstrated to be expressed during organogenesis-most notably in the head, the limbs and the ventrolateral body wall. To investigate the role of goosecoid in embryonic development, we have inactivated the gene by gene targeting to generate mice mutant for the goosecoid gene. Mice that are homozygous for the goosecoid mutation do not display a gastrulation phenotype and are born; however, they do not survive more than 24 hours. Analysis of the homozygotes revealed numerous developmental defects affecting those structures in which goosecoid is expressed during its second (late) phase of embryonic expression. Predominantly, these defects involve the lower mandible and its associated musculature including the tongue, the nasal cavity and the nasal pits, as well as the components of the inner ear (malleus, tympanic ring) and the external auditory meatus. Although the observed phenotype is in accordance with the late expression domains of goosecoid in wild-type embryos, we suggest that the lack of an earlier phenotype is the result of functional compensation by other genes.

Animals↗