[A case of early rectal cancer with the sign of Leser-Trélat].
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Adenocarcinoma↗
Biomedical subjects
K Yamamura
Publications and source records attributed to K Yamamura.
The 3' enhancer region determines the B/T specificity and pro-B/pre-B specificity of immunoglobulin V kappa-J kappa joining.
Using transgenic substrates, we found that the immunoglobulin kappa gene 3' enhancer (E3') acts as a negative regulator in V kappa-J kappa joining. Although the E3' was originally identified as a transcriptional enhancer, it acts in a suppressive manner for recombinational regulation. Base substitution analysis has shown that the PU.1-binding site within the E3' regulates the B/T specificity of V kappa-J kappa joining. In a substrate with a mutated PU.1-binding site (GAGGAA to TCTTCG), V kappa-J kappa joining occurred not only in B cells, but also in T cells. The E3' region is also responsible for determining the pro-B/pre-B specificity of V kappa-J kappa joining. When the E3' region was deleted, kappa gene rearrangement actively occurred at the early pro-B stage of B cell development: nongermline (N) nucleotides were common at recombination junctions.
Animals↗
Identification of cell binding sites in the laminin alpha 1 chain carboxyl-terminal globular domain by systematic screening of synthetic peptides.
The laminin alpha 1 chain carboxyl-terminal globular domain has been identified as a site of multiple biological activities. Using a systematic screening for cell binding sites with 113 overlapping synthetic peptide beads that covered this domain, we found 19 potential active sequences. Corresponding synthetic peptides were evaluated for direct cell attachment, spreading, and inhibition of cell spreading to a laminin-1 substrate using several cell lines. Five peptides (AG-10, AG-22, AG-32, AG-56, and AG-73) showed cell attachment activities with cell-type specificities. Cell spreading on AG-10 was inhibited by beta 1 and alpha 6 integrin antibodies and on AG-32 was inhibited by beta 1, alpha 2, and alpha 6 integrin antibodies. In contrast, cell adhesion and spreading on peptide AG-73 were not inhibited by these antibodies. The minimum active sequences of AG-10, AG-32, and AG-73 were determined to be SIYITRF, IAFQRN, and LQVQLSIR, respectively. These sequences are highly conserved among the different species and different laminin alpha chains, suggesting that they play a critical role for biological function and for interaction with cell surface receptors.
Amino Acid Sequence↗
Molecular cloning and characterization of mouse HS1.
Here we report the cloning of a cDNA and a genomic DNA encoding the mouse homolog of human HS1, a hematopoietic cell-specific protein-substrate of non-receptor type protein-tyrosine kinase(s). Sequence analysis of the mouse HS1 cDNA revealed that it is highly homologous to human HS1 (total percent match = 84%) especially in the amino-terminal half, which contains unique repeating motifs, and in the carboxyl-terminal Src-homology 3 domain. As is the human counterpart, the mouse HS1 gene is expressed exclusively in hematopoietic cells. Genomic fragments covering most of the HS1 gene were isolated and used to map this gene to mouse chromosome 16.
Adaptor Proteins, Signal Transducing↗
Importance of ornithine transcarbamylase (OTC) deficiency in small intestine for urinary orotic acid excretion: analysis of OTC-deficient spf-ash mice with OTC transgene.
We report the effect of the ornithine transcarbamylase (OTC) transgene composed of 1.3 kb of the 5' flanking region of the rat OTC gene fused to rat OTC cDNA on urinary orotic acid excretion in OTC-deficient spf-ash (sparse-fur with abnormal skin and hair) mice during overnight-starvation and nitrogen loading. During starvation, spf-ash mice with about 6% and 2% of control levels of OTC activity in the liver and small intestine excreted a large amount of orotic acid in the urine. Transgenic spf-ash mice with about 10% and 30% of the control OTC activities in the liver and small intestine did not excrete more than the normal level of orotic acid. Accidental parasitization of transgenic spf-ash mice with ticks (Myocoptes musculinus) resulted in decrease of the OTC activities in the liver and small intestine to the levels in spf-ash mice, and increased excretion of orotic acid. During extermination of the ticks, the mice showed varied levels of OTC activity and orotic acid excretion. On nitrogen loading, transgenic spf-ash mice as well as spf-ash mice excreted larger amounts of orotic acid, while control mice showed no increase in its excretion. The levels of urinary orotic acid were inversely correlated to the logarithms of the OTC activities in the liver and small intestine, the correlation being significantly higher with intestinal OTC than with hepatic OTC activity. These results suggest that the level of OTC activity in the small intestine is important for production of orotic acid.
Animals↗
Sustained release of basic fibroblast growth factor from the synthetic vascular prosthesis using hydroxypropylchitosan acetate.
We designed a model vascular prosthesis consisting of expanded polytetrafluoroethylene (Gore Tex) loaded with basic fibroblast growth factor (bFGF), and studied its in vivo bFGF release behavior. To control the release rate of bFGF, biodegradable hydroxypropylchitosan acetate (HPCHA) was also incorporated into the Gore Tex disks with bFGF. HPCHA was dissolved in bFGF solution (180 micrograms/ml) at a concentration of 4% (wt/vol). A Gore Tex tube was cut into a length of about 5 cm and one end was sealed with a vascular clamp. The tube was then filled with resulting solution under appropriate pressure until the solvents seeped through the pores. The tube loaded with bFGF solution was freeze-dried and was cut into disks (0.75 cm in diameter). bFGF content in a HPCHA-free Gore disk was 2.05 +/- 0.32 micrograms (SE, n = 5). bFGF content in a HPCHA Gore disk was 2.71 +/- 0.41 micrograms (SE, n = 5). In an in vivo study in which the bFGF loaded Gore Tex disk was implanted in rabbit skin pockets, almost 100% of bFGF from HPCHA-free disks was released within 24 h, whereas some 60% remained after 24 h in the HPCHA-loaded disks. HPCHA is a useful biodegradable carrier for controlling the release rate of the drug from the synthetic vascular prosthesis.
Animals↗
Prevention of bone loss by percutaneous estradiol implants in ovariectomized rats.
This study was conducted to investigate whether hydroxyapatite (HAP) is appropriate as a percutaneous drug carrier for estradiol (E2) for the suppression of bone loss. Ten-week-old female Sprague-Dawley rats were subjected either to bilateral ovariectomy (OVX) or to sham surgery (control). Ovariectomized rats were implanted percutaneously with E2-HAP disks containing low, medium or high doses of estradiol (50, 250, or 500 micrograms E2/rat, respectively). Ovariectomized rats without implant and OVX rats implanted only with HAP served as additional controls. All rats were sacrificed 90 days after surgery. At the end of the experiment, bone mineral density of the lumbar spine was measured by dual energy X-ray absorption, and serum E2 was assayed by radioimmunoassay. The bone mineral density of OVX and HAP-treated OVX rats decreased by 18% compared to sham surgery rats, but decreased by only 13, 7, and 3% in rats treated with 50, 250, and 500 micrograms E2/rat, respectively. The in vitro release of E2 from E2-HAP devices was determined by an HPLC method. Estradiol release from the HAP devices followed almost a zero-order kinetics. Estradiol remained intact in E2-HAP implants for up to six months when stored at 5, 25, and 40 degrees C. This study indicates that E2-HAP implants are effective in suppressing bone loss in the spine of OVX rats in a dose-dependent manner.
Animals↗
Defective IL-5-receptor-mediated signaling in B cells of X-linked immunodeficient mice.
Murine (m) IL-5 induces proliferation and differentiation of both Ly-1+ B cells and activated conventional B cells. X-linked immunodeficient (XID) mice do not respond to thymus-independent type II antigens, and have an abnormal response to a variety of activation signals through Ig receptors, CD40 and cytokine receptors. Furthermore, XID mice show a B cell specific defect, reflected in decreased numbers of IL-5R alpha+ B cells and reduced responsiveness of IL-5R alpha+ B cells to mIL-5. We generated IL-5R alpha transgenic (5R alpha-Tg) mice in which B cells expressed recombinant IL-5R alpha. We crossed male 5R alpha-Tg mice with female XID mice and used their offspring to determine the IL-5 responsiveness of these B cells. All B cells of F1 male mice carrying the xid gene together with the transgene expressed the recombinant IL-5R alpha. However, those mice lacked Ly-1 B cells and their B cells acquired responsiveness to mIL-5. Interestingly, XID-5R alpha-Tg B cells, but not XID B cells, acquired mIL-5 proliferative and Ig-secretory responsiveness only in the presence of suboptimal doses of lipopolysaccharide. Stimulation of these B cells with mIL-5 plus phorbol myristate acetate induced proliferation, but not Ig secretion. These results indicate that the impaired mIL-5 responsiveness of B cells in XID mice is due to an abnormality of IL-5R-mediated signaling which may correlate with the xid gene mutation, alteration of a single amino acid of Bruton's tyrosine kinase.
Agammaglobulinaemia Tyrosine Kinase↗
A 6-kb upstream region of the human transthyretin gene can direct developmental, tissue-specific, and quantitatively normal expression in transgenic mouse.
To ascertain whether a 6-kb upstream region of the human transthyretin (TTR) gene contains the cis-element(s) required for proper specificity and level of expression, transgenic mice carrying the human mutant TTR gene containing either 6-kb (6.0-hMet30) or 0.6-kb (0.6-hMet30) of the upstream region were produced and studied. The 6.0-hMet30 gene was expressed in the yolk sac, liver, and choroid plexus, where the mouse endogenous TTR gene is also expressed. In contrast, expression of the 0.6-hMet30 gene was restricted to the yolk sac and liver. The expression levels of the 6.0-hMet30 gene in the liver and serum were similar to those of the mouse TTR gene, and about 10-fold those of the 0.6-hMet30 gene. Before birth, the developmental profiles of the expression of both transgenes in each tissue were similar to those of the mouse TTR gene. However, the expression levels of the 6.0-hMet30 gene in the liver and serum increased after birth to reach adult levels at an age of 4 weeks, while expression of the 0.6-hMet30 gene remained at a low level after birth. These results suggest that the 6-kb upstream sequence contains the cis-elements required for developmental, tissue-specific, and quantitatively normal expression.
Animals↗
Copy-dependent and position-independent expression of rat aldolase A gene.
In order to understand the molecular mechanisms of the temporal and spatial differences of gene expression in higher organisms, rat aldolase A gene carrying two distinct promoters was introduced into fertilized eggs and the resulting transgenic mice were analyzed. The transgene expression is tissue-specific and is developmentally regulated. In addition, the expression is regulated in a copy-dependent manner irrespective of where the transgene is integrated, suggesting that a mechanism excluding the effect of the integration site exists within the transgene itself. To explore the conformational change of this gene in the genome, the DNase I hypersensitive sites of the gene were examined. Three sites (DHS-1,2, and 3) were identified upstream and downstream of the gene and these sites were retained in the transgene as well as in the gene observed endogenously.
Animals↗
Prevention of vascular graft infection by sisomicin incorporated into fibrin glue.
To examine the efficacy of sisomicin (SISO) incorporated into fibrin glue (FG) for the prevention of graft infection in animal models, the susceptibility to infection of Dacron grafts (control) and SISO-FG Dacron grafts following the inoculation of Staphylococcus aureus or S. epidermidis was compared. The results showed that SISO-FG Dacron grafts displayed resistance to graft infection.
Animals↗
Ophthalmic preservatives as absorption promoters for ocular drug delivery.
The effects of ophthalmic preservatives on the drug permeability through isolated ocular membranes of albino rabbits were investigated using a two-chamber glass diffusion cell. Tilisolol and fluorescein isothiocyanate (FITC)-dextrans (average molecular weights 4400 and 9400 Da; FD-4 and FD-10, respectively) were used as model penetrants of ophthalmic beta-blockers and peptide drugs. Preservatives significantly enhanced the corneal penetration of not only tilisolol but also FITC-dextrans. Especially, benzalkonium chloride increased the corneal permeability of FD-4 and FD-10 by 28.8 and 37.1 times, respectively. These results indicate the usefulness of ophthalmic preservatives as absorption promoters for the ocular delivery of beta-blockers and hydrophilic macromolecules. Preservatives also enhanced the conjunctival permeability of tilisolol, FD-4 and FD-10. The promoting effect of preservatives on the conjunctival drug penetration was smaller than that on the corneal one. Preservative increased the ratio of corneal to conjunctival permeability of tilisolol, FD-4 and FD-10. The different responses of corneal and conjunctival drug penetrations to ophthalmic preservatives may be useful to control the extent and pathway for the ocular and systemic absorptions of instilled drugs.
Absorption↗
Effect of levofloxacin-albumin Dacron graft on graft infection.
The susceptibility of Dacron grafts to infection is compared with Dacron grafts applied with levofloxacin-bonded albumin (LVFX-ALB) following the inoculation of 10(7) cells Staphylococcus aureus in rats. Staphylococcus epidermidis was inoculated in the same manner. While the control grafts were infected at the time of removal, the LVFX-ALB Dacron grafts resisted infection, thus demonstrating their effectiveness.
Animals↗
Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin.
To investigate the relationship between human islet amyloid polypeptide (IAPP)/amylin expression and islet amyloid deposits in the pathogenesis of human non-insulin-dependent diabetes mellitus (NIDDM), we developed transgenic mice using a human IAPP cDNA connected to an insulin promoter. Ribonucleic acid blotting and immunohistochemistry revealed the expression of the transgene in the pancreatic beta cells. Immunogold electron microscopy showed that beta-secretory granules contained the human C-terminal flanking peptide of the IAPP precursor. Reverse-phase HPLC demonstrated human and mouse IAPP amide in the pancreas. Electron microscopy showed the accumulation of fibril-like material in a considerable number of beta-secretory granules. These results suggest that in transgenic mice, the human IAPP precursor is expressed in beta cells and becomes normally sorted into beta-secretory granules in which normal conversion to mature human IAPP takes place. The human IAPP molecules, because of their amyloidogenesis, aggregate into amyloid fibrils in secretory granules. Glucose tolerance was normal at 7 months old and islet amyloid was not observed. A longer time may be required for islet amyloid deposits and hyperglycemia to develop in mice. Our working hypothesis is that in human NIDDM, IAPP aggregates into amyloid fibrils in beta-secretory granules, and that the fibrils are released into the extracellular space and islet amyloid deposits become substantial with time.
Amyloid↗
Ocular permeability of FITC-dextran with absorption promoter for ocular delivery of peptide drug.
The purpose of this study is to characterize an ocular permeability of FITC-dextran, as a model of peptide drug, and to evaluate the effects of absorption promoters on the ocular permeability of FITC-dextran. The in vitro penetrations of FITC-dextrans (average molecular weight 4400 and 9400: FD-4 and FD-10) were measured across the isolated corneal and conjunctival membranes of albino rabbits using a two-chamber glass diffusion cell. The corneal permeabilities of FD-4 and FD-10 were much lower than the conjunctival permeabilities. Scraping of corneal epithelium extremely increased the corneal permeabilities. The penetration parameters were estimated according to Fick's equation. Absorption promoters such as EDTA, taurocholic acid, benzalkonium chloride and saponin significantly increased corneal permeabilities of FD-4 and FD-10. Saponin showed the highest promoting activity. Conjunctival permeabilities of FD-4 and FD-10 were also enhanced by absorption promoters although the improvements of conjunctival permeabilities by absorption promoters were smaller than those of corneal permeabilities. Ratios of corneal to conjunctival permeabilities were enhanced by absorption promoters. These results indicate that an ocular delivery of instilled hydrophilic macromolecule is markedly low and a selective use of absorption promoter can improve the extent and pathway of its ocular absorption.
Absorption↗
[Spontaneous dissecting aneurysm of the superficial temporal artery: a case report].
Aneurysms of the superficial temporal artery are rare, and usually traumatic in origin. We present a very rare case of spontaneous dissecting aneurysm of the superficial temporal artery in a 46-year-old man. The patient had pulsatile headache in the right temporal region, and a pulsatile mass in the same region. His headache gradually worsened for which he came to our hospital. On examination, there was a pulsatile mass of 1.5cm x 3cm at the right temporal region, which disappeared when the main trunk of superficial temporal artery was compressed. There was no neurological abnormality. On computed tomographic examination, there was a spotty high density area in the right extracranial region corresponding to the right superficial temporal artery, which was strongly enhanced after contrast medium administration. On MRI examination, the same area showed high intensity, but at inner space there was signal loss on T1WI, T2WI and PDWI. Angiography showed an aneurysmal dilatation at the right superficial temporal artery and both the true lumen and the false lumen were recognized. Excision of the aneurysm under local anesthesia was performed. His complaints disappeared completely post-operatively, and the skin color of that region retained its normal texture. Histopathological examination of the specimen showed hypertrophic intima with fibroblasts, and absence of internal elastic lamina. There was hematoma outside of the intima, but no deposits of hemosiderin. On account of the above findings, the lesion was diagnosed as a spontaneous dissecting aneurysm of the superficial temporal artery.
Aortic Dissection↗
Transgenic mouse model of familial amyloidotic polyneuropathy type I: its production, biological features, and usefulness.
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Amyloid↗
[Ruptured distal anterior cerebral artery aneurysm and diagnostic dyspraxia: a case report].
A case of ruptured distal anterior cerebral artery aneurysm presenting with diagnostic dyspraxia is presented. A 54-year-old female was referred to our hospital with the complaint of sudden onset of headache followed by disturbance of consciousness. CT and MRI revealed subarachnoid hemorrhage with hematomas in the interhemispheric fissure and the supracallosal area, and CAG revealed a left-sided callosomarginal artery aneurysm. During and after hospitalization, she showed diagnostic dyspraxia characterized by behavior of both her hands opposite to what might be expected e.g. when she tried to pick up a bowl, both her hands moved forward and held it at once; she wiped her head and face with toilet paper after urination. At times her hands behaved in opposite ways. For example, while folding cloths, her right hand tended to fold them while the left hand tended to unfold them; when she put on a sweater, as the right hand put it on, the left hand took it off; when she put her shirt into her trousers, one hand pushed it in while the other hand pulled it out. This unusual behavior was considered to be caused by the impairment of the corpus callosum due to compression by the hematoma. It disappeared gradually over a period of one year. Involuntary motor behavior of the left hand while the right hand is in voluntary action is known as diagnostic dyspraxia. Although this symptom has rarely been reported so far in cases of ruptured distal anterior cerebral artery, it may become noticed more frequently through careful observation.
Aneurysm, Ruptured↗