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Biomedical subjects

G Yamada

Publications and source records attributed to G Yamada.

At least 37 records · Page 2Linked to original sources

Possible contaminant origins of the red cosmetics decorating ancient burial sites in Japan.

Marker elements were estimated from the red cosmetics collected from different ancient burials and mine ruins in three separate districts of Japan. Element levels were displayed in reference to the relative amount to sulfur (RA/S), by which the cosmetics were divided into five types: I--a low Hg/S with a low Fe/S; II--both moderate Hg/S and Fe/S; III--a moderate Hg/S with a high Fe/S; III 2--a high Hg/S with a moderate Fe/S; IV--a high Hg/S with a high Fe/S. The cosmetics can be further characterized by referring to other contaminants such as Zn, Cu, and Mn. These combined analyses with contaminant metals were capable of characterizing the origins of the cosmetics; it is useful to compare them to each other. The cosmetics were identified as being due to several groups of contaminants from ancient mines in Japan, and also with this system analysis of the markers it is possible to identify them from neighboring countries.

Archaeology↗

Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy.

BACKGROUND: Previous studies on the effect of interferon therapy on the incidence of hepatocellular carcinoma have not sufficiently assessed degree of liver fibrosis, a major risk factor for hepatocellular carcinoma. OBJECTIVE: To evaluate the effect of interferon therapy on incidence of hepatocellular carcinoma, adjusting for risk factors, including the degree of liver fibrosis. DESIGN: Retrospective cohort study. SETTING: Seven university hospitals and one regional core hospital in Japan. PATIENTS: 2890 patients with chronic hepatitis C who had undergone liver biopsy since 1986. Of these patients, 2400 received interferon and 490 were untreated. MEASUREMENTS: The degree of liver fibrosis was assessed from stage F0 (no fibrosis) to stage F4 (cirrhosis). Response to interferon was determined virologically and biochemically. Screening for development of hepatocellular carcinoma was performed periodically during an average follow-up of 4.3 years. Effect of interferon therapy on the risk for hepatocellular carcinoma was analyzed by using Cox proportional hazards regression. RESULTS: Hepatocellular carcinoma developed in 89 interferon-treated patients and in 59 untreated patients. Among untreated patients, the annual incidence of hepatocellular carcinoma increased with the degree of liver fibrosis, from 0.5% among patients with stage F0 or F1 fibrosis to 7.9% among patients with stage F4 fibrosis. The cumulative incidence in treated and untreated patients differed significantly for patients with stage F2 fibrosis (P = 0.0128) and for those with stage F3 fibrosis (P = 0.0011). In multivariate analysis, interferon therapy was associated with a reduced risk for hepatocellular carcinoma (adjusted risk ratio, 0.516 [95% CI, 0.358 to 0.742]; P < 0.001), especially among patients with sustained virologic response (risk ratio, 0.197 [CI, 0.099 to 0.392]), among those with persistently normal serum alanine aminotransferase levels (risk ratio, 0.197 [CI, 0.104 to 0.375]), and among those with alanine aminotransferase levels less than two times the upper limit of normal (risk ratio, 0.358 [CI, 0.206 to 0.622]). CONCLUSIONS: Interferon therapy significantly reducesthe risk for hepatocellular carcinoma, especially among virologic or biochemical responders.

Alanine Transaminase↗

A BMP-inducible gene, dlx5, regulates osteoblast differentiation and mesoderm induction.

Bone morphogenetic proteins (BMPs), members of the transforming growth factor beta superfamily, have been identified by their ability to induce cartilage and bone from nonskeletal cells and have been shown to act as a ventral morphogen in Xenopus mesoderm. We isolated a murine homeobox-containing gene, distal-less 5 (mDlx5), as a BMP-inducible gene in osteoblastic MC3T3-E1 cells. Stable transfectants of MC3T3-E1 that overexpress mDlx5 mRNA showed increase in various osteogenic markers, a fourfold increase in alkaline phosphatase activity, a sixfold increase in osteocalcin production, and appearance in mineralization of extracellular matrix. Furthermore, mDlx5 was induced orthotopically in mouse embryos treated with BMP-4 and in fractured bone of adult mice. Consistent with these observations, we also found that injection of mDlx5 mRNA into dorsal blastomeres enhanced the ventralization of Xenopus embryos. These findings suggest that mDlx5 is a target gene of the BMP signaling pathway and acts as an important regulator of both osteogenesis and dorsoventral patterning of embryonic axis.

3T3 Cells↗

Fgf-8 determines rostral-caudal polarity in the first branchial arch.

In mammals, rostral ectomesenchyme cells of the mandibular arch give rise to odontogenic cells, while more caudal cells form the distal skeletal elements of the lower jaw. Signals from the epithelium are required for the development of odontogenic and skeletogenic mesenchyme cells. We show that rostral-caudal polarity is first established in mandibular branchial arch ectomesenchymal cells by a signal, Fgf-8, from the rostral epithelium. All neural crest-derived ectomesenchymal cells are equicompetent to respond to Fgf-8. The restriction into rostral (Lhx-7-expressing) and caudal (Gsc-expressing) domains is achieved by cells responding differently according to their proximity to the source of the signal. Once established, spatial expression domains and cell fates are fixed and maintained by Fgf-8 in conjunction with another epithelial signal, endothelin-1, and by positional changes in ectomesenchymal cell competence to respond to the signal.

Animals↗

Middle ear defects associated with the double knock out mutation of murine goosecoid and Msx1 genes.

A number of developmental regulatory genes, including homeobox genes, are dynamically expressed in the mammalian cephalic ectomesenchyme during craniofacial morphogenesis. Owing to the vast amount of gene knock out experiments, functions of such genes are now being revealed in the mammalian skeletal patterning process. The murine goosecoid (Gsc) and Msx1 genes are expressed during craniofacial development and each mutant mouse displays intriguing facial abnormalities including those of middle ear ossicles, suggesting that both genes play roles in spatial programming of craniofacial regions. In order to examine whether these genes could function in concert to direct particular craniofacial morphogenesis, double knock out mice were analyzed. The phenotype of the double mutant mice was restricted to the first arch derivatives and was apparently additive of the single gene mutant mice, implying region specific genetic interactions of these homeobox genes expressed in overlapping regions of middle ear forming ectomesenchyme. Our results also suggested that the patterning of distal portions of the malleus depends on the tympanic membrane, for which normal expressions of both the genes are prerequisite.

Animals↗

Retinoic acid teratogenicity: the role of goosecoid and BMP-4.

Retinoic acid (RA) plays a pivotal role during vertebrate development, both as morphogen and as potent teratogen. While RA function in axial development has been extensively studied, little is known about the genetic control of RA teratogenicity. The knockout of the homeobox gene goosecoid in the mouse revealed similarities to RA induced embryopathy. We show that RA treatment of mouse gastrula embryos in vitro and of E10.5 embryos in utero led to a rapid but transient down-regulation of goosecoid expression. Repression was dependent on retinoid X receptors (RXR). BMP-4 was repressed by RA-treatment as well, both in embryos and in F9 teratocarcinoma cells. Our data suggest that both goosecoid and BMP-4 function as mediators of RA teratogenicity in mouse embryos.

Animals↗

[Effect of rush immunotherapy (RIT) on Hymenoptera allergy].

In our country approximately forty people die every year from anaphylaxis caused by hymenoptera stings. Between 1988 and 1996, 48 patients, who had experienced a systemic reaction to hymenoptera sting and were proved to have specific IgE antibodies to wasp, yellow or both (RAST score > or = 2), received rush immunotherapy (RIT) using venom extracts in our hospital. Fifteen patients had re-sting after RIT. Fourteen out of the 15 patients showed only local reaction to the hymenoptera re-sting and one patient had mild generalized symptoms. Although one patient showed mild generalized uriticaria during RIT, no adverse reaction occurred during and after RIT in the other subjects. Follow-up studies on the titers of serum total IgE antibodies and hymenoptera specific IgE and IgG4 antibodies revealed that total and specific IgE antibodies transiently increased one month after RIT and returned to their baseline values by 6 months after RIT, while specific IgG4 antibodies continued to gradually increase up to al least 3 years after RIT. These results demonstrates that RIT is effective in prevention of a systemic reaction to hymenoptera re-sting and an increase in the titer of hymenoptera specific IgG4 antibodies may at least partly explain the efficacy of RIT.

Adult↗

Malformation of trachea and pelvic region in goosecoid mutant mice.

The homeobox gene goosecoid is expressed in the Spemann organizer tissue of gastrulating vertebrate embryos, and in the craniofacial region and appendicular skeleton during organogenesis. The goosecoid knockout mutant mouse revealed defects related to the second phase of expression. Here we describe new expression sites in the developing trachea and external genitalia, and in the developing shoulder and hip joint with their associated ligaments and muscles. We show that mutant mice display abnormalities in the forming trachea and appendicular skeleton related to these sites of gene expression. In addition, we discuss evidence for the existence of at least three goosecoid genes in vertebrates, which may account for the lack of a defect of axial patterning in goosecoid mutant mice.

Animals↗

Trace elements found to be variable in two coral reef species, Heliofungia actiniformis and Galaxea fascicularis, collected from the Ryukyu Islands.

Biominerals and metals of intertidal corals of two species (Heliofungia actiniformis, Quoy and Gaimard; Galaxea fascicularis, Linnaeus), collected from the Iriomote Island of Ryukyu, were examined with an inductively coupled plasma atomic emission spectrometer (ICP-AES). Twelve elements were detectable in the coralline skeletons dissected radially along the growth axis. The relative content (RC) of Hg periodically fluctuated and was minimum at the hollow sites of the coralline slab of Heliofungia sp., corresponding to the cyclic growth. There were two types of elements: constant elements and variable elements along the growth axis. RCs of Ca, Mg, Al, Si, and P were nearly constant. RCs of Fe, Mn, Cu, and Ba were variable, but not as regularly changed as Hg. There were positive mass correlations of Hg to Mn, Cu and Zn, but not to Ba and Fe. In contrast, these relationships were not prominent and were likely degraded by aging in the skeleton of Galaxea sp., suggesting a different mode from that of the Heliofungia sp.

Animals↗

The prechordal midline of the chondrocranium is defective in Goosecoid-1 mouse mutants.

Gsc-1 expression marks cells with Spemann organizer, or axis-inducing, activity in the vertebrate gastrula. Gsc-1 knockouts, however, did not display phenotypes related to the early phase of expression. In this paper, additional phenotypes for the Gsc-1 mouse mutant are presented. Examination of the base of the cranium in the dorsal view revealed fusions and deletions in the midline of the prechordal chondrocranium. These defects were correlated with the sites of expression of Gsc-1 in the prechordal plate/foregut endoderm in the day 7.5/8.5 embryo. Gsc-1 expression in proximal limb buds was correlated with malformations of the shoulder and hip articulations. In addition, ribs in the seventh cervical vertebra were observed with low penetrance. The role of Gsc-1 during gastrulation and axial development is discussed in relation to possible compensatory interactions with other genes such as HNF-3beta and the recently identified Gsc-2 and Gsc-3 genes.

Amino Acid Sequence↗

Use of bronchopulmonary lavage for eliminating inhaled fume particles from a patient with arc welder's lung.

A 42-year-old man, who had worked as a welder for 20 years, was admitted to our hospital complaining of a dry cough. A chest radiograph showed diffuse small nodular shadows and chest computed tomography revealed small patchy opacities. A transbronchial lung biopsy specimen showed welding fume particles mainly located in alveolar space with mild fibrosis of alveolar septa. In order to prevent further fibrosis, bronchopulmonary lavage (BPL) was performed to eliminate the fume particles. The amount of iron particles derived from the total lavage fluid was 911.7 mg.

Adult↗

Aberrant regulation of bone trace elements in motheaten and osteopetrosis mutant mice.

Increasing numbers of genetic diseases involving bone development and models for these diseases have been identified recently. Analysis of these bone diseases have revealed that regulated action of multiple growth factors and subsequent signal transduction are essential for normal bone formation. In this paper, two murine mutant mice viable motheaten and osteopetrosis are analyzed. Mice with the recessive 'viable motheaten' mutation express a severe immunodeficiency syndrome and bone defects. Mutations at the motheaten locus were shown to be the result of aberrant splicing of the gene encoding hematopoietic cell phosphatase (Hcph). Mice homozygous for the osteopetrosis mutation develop congenital osteopetrosis due to a severe deficiency of osteoclasts. It has been recognized that bone trace element composition analysis helps to define bone-related physiological conditions. We have analyzed bone trace element composition in viable motheaten and osteopetrosis mutant animal models in this study. In order to gain insights into the effects of particular genetic defects on bone trace element composition, inductively coupled plasma atomic emissions spectrometry (ICP-AES) analysis was performed. Marked changes in bone trace element levels were found in limb bones of viable motheaten and osteopetrosis mutant mice. An assessment of these trace element spectrum in the two mutant models with respect to each genetic defects are discussed in this paper.

Animals↗

[Peripheral primitive neuroectodermal tumor in parietal pleura].

A 19-year-old woman was admitted to Kushiro city general hospital due to chest pain and dyspnea. Chest radiographs and computed tomographic scan showed a large intrathoracic mass adjacent to the pleura. Angiographs disclosed feeding veins of the tumor arising from lateral thoracic artery. Fine-needle aspiration cytology of the tumor revealed small round cells with a large nuclear/cytoplasmic ratio. Immunocytochemical study demonstrated that the tumor cells were positive for neuron-specific enolase and MIC 2 gene product. The diagnosis was primitive neuroectodermal tumor of the parietal pleura (also known as Askin tumor). Chemotherapy combined with peripheral blood stem cell transplantation reduced the size of the tumor significantly. However, multiple bone metastasis recurred, and the patient died 35 months after the start of therapy.

Adult↗

Dysregulation of trace element composition in ovariectomized cynomolgus monkey bones.

One of the challenging issues in modern biomedical science is the increasing number of osteoporosis patients due to the expansion of elderly populations. Among aging-related pathogenic changes, alterations in bone function and skeletal pathogenesis is a particularly important issue of concern. Osteoporosis is one of the most serious bone-related pathogenic states, as it causes serious loss of quality of life. Alterations in estrogen levels in accordance with aging are one of the key risk factors for osteoporosis. Complexed estrogen actions on bones can be traced by analyzing bone mineral components, as those elements accumulate as mineral complexes, reflecting the context of multiple cellular reactions such as bone resorption/osteogenesis. We have analyzed bone trace element composition in ovariectomized (OVX-treated) Cynomolgus monkey models in this study. In order to gain insights into the effects of such defects on bone trace element composition, inductively coupled plasma atomic emissions spectrometry (ICP-AES) analysis was performed. Marked changes in bone trace element levels were found in vertebral bones of OVX-treated Cynomolgus monkeys. An assessment of these trace element spectra in OVX model animals is discussed. These results could provide useful markers for understanding the physiological states of bones in postmenopausal women.

Animals↗

Different element ratios of red cosmetics excavated from ancient burials of Japan.

Marker elements of red cosmetics, collected from ancient burials of Matsuyama, Tokushima and Nara Japan, were determined by emission spectrometry (ICP/AES). The mass ratios of Hg, Fe, Cu, and Zn were different between samples. Element levels were compared with reference to relative amounts of sulfur. Of the possible contaminants from the bone and sand of burials, the relative amounts of Hg and Fe to S were most commonly available to evaluate the difference between the cosmetics. The cosmetics were divided into four groups; type I (high Hg with less Fe), type II (both moderate Hg and Fe), type III (moderate Hg with high Fe) and type IV (less Hg with high Fe). The main constituents of cosmetics are mercury sulfide (cinnabar) or ferric oxide mixed with trace metals. Zinc contents differ between the Fe and Hg amounts for the three areas. Cosmetic compositions varied with each burial site, suggesting that they were derived from different mines of ancient Japan.

Anthropology↗

Correlation between loss of middle ear bones and altered goosecoid gene expression in the branchial region following retinoic acid treatment of mouse embryos in vivo.

The homeobox gene goosecoid marks the Spemann organizer in vertebrate gastrula embryos, and is expressed in the craniofacial region, body wall and limbs during organogenesis. Mouse mutants of goosecoid displayed a variety of phenotypes related to the expression pattern at mid-embryogenesis. These defects included loss of the tympanic ring and malformation of the malleus, phenotypes which were reminiscent of the teratogenic effects of retinoic acid (RA). Here we investigated the correlation of goosecoid gene expression and RA-teratogenicity following treatment of mouse embryos in vivo at embryonic day (E) 8 + 5 h. We found that goosecoid was specifically affected at E10.5 in branchial arches I and II. Expression was either reduced to background levels or restricted to the branchial cleft region. This change in goosecoid gene expression correlated with a loss of middle ear ossicles and a partial or complete deletion of the tympanic ring, suggesting a role for goosecoid in executing the RA teratogenic effects.

Animals↗