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Biomedical subjects

K Yamamura

Publications and source records attributed to K Yamamura.

At least 109 records · Page 6Linked to original sources
PubMed1998

[Rare intra-abdominal complications of a ventriculoperitoneal shunt: report of three cases].

Three cases of rare intra-abdominal complications of ventriculoperitoneal shunt (VPS) surgery are reported. Case 1 was a 32-year-old male who had undergone VPS surgery for hydrocephalus following meningitis on July 10, 1980. Two weeks later he developed fever and a cystic mass about 10 cm in diameter in the right hypochondrium. Shuntography and a barium enema study demonstrated a pseudocyst at the distal end of the shunt. The cyst wall was excised, the peritoneal tube removed, and VPS converted to a ventriculoatrial route following which the pseudocyst resolved. Case 2 was a 49-year-old female who developed hydrocephalus following subarachnoid hemorrhage, and VPS surgery was performed on March 10, 1989. Two weeks later, she developed fever and right upper abdominal pain. Abdominal x-ray and CT scan revealed a right subdiaphragmatic abscess. The abscess was drained and the shunt system was removed on April 4. VPS was placed again on April 21 without further complications. She was symptom free for the next 7 years. Case 3 was a 57-year-old female who presented in a semicomatose state after falling from bed on May 5, 1995. CT scan showed left-sided acute subdural hematoma (ASDH) for which surgery was performed. Her neurological status improved postoperatively. She eventually developed hydrocephalus and left-sided subdural effusion for which right VPS and left subduroperitoneal shunt (SPS) surgery was performed on January 25, 1996. The peritoneal end of the tube of the SPS protruded out of the anus one and a half year after shunt placement. The entire SPS system was removed as there was no more collection in the subdural space. We reviewed the literature and discussed the pathophysiology involved in the development of intraabdominal complications following VPS.

Abdominal Injuries↗
PubMed1997

Studies on the microsomal cytochrome P450s in the livers of carcinogen-resistant and sensitive rats during long-term administration of 3'-methyl-4-dimethylaminoazobenzene.

Time-course studies on the microsomal cytochrome P450s in the livers of carcinogen-resistant (DRH) and sensitive (Donryu) rats were carried out during a long-term administration of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). Total contents of the microsomal cytochrome P450s were gradually reduced with time in the Donryu rat livers, while those in the DRH rats did not alter significantly under these conditions. The activities of several isoforms of cytochrome P450 (CYP1A1, CYP1A2, and CYP2E1) were determined separately during these experimental periods. However, we could not obtain satisfactory evidence which may explain the different susceptibility to chemical carcinogenic actions in the livers between DRH and Donryu rats. Lower total contents of cytochrome P450s in the Donryu rats during the later stage may be due to the hepatic injuries caused by long-term administration of 3'-Me-DAB.

Animals↗
PubMed1997

Subcutaneous tissue distribution of vancomycin from a fibrin glue/Dacron graft carrier.

We investigated the tissue distribution of vancomycin (VCM) incorporated in fibrin glue (FG) in a rat model. One VCM-loaded FG Dacron graft (VCM-FG, VCM 0.6 mg/ graft) was implanted in the subcutaneous tissue of the anterior abdominal wall of each rat. VCM was injected intravenously at an equal dose (0.6 mg/rat) after implantation of one control graft (without VCM-FG). After the implantation and the iv injection of an equal dose of VCM (0.6 mg/rat), the tissue distribution of VCM for up to 24 h was determined through analysis of the implanted VCM-FG grafts, which released VCM over a 24 h period. The area under the VCM concentration-time curve (AUC) of the tissue was 89.58 micrograms.h/g after the implantation of the VCM-FG graft, and 7.40 micrograms.h/g after the iv injection of VCM, respectively. The targeting index of the tissue, defined as the ratio of AUC after the implantation of the VCM-FG graft to that after VCM iv injection, was 12.11. None of the six VCM-FG Dacron grafts after implantation became infected following inoculation with S. aureus ATCC 25923 (0.1 mL 10(8) CFU/mL). These results suggest that this VCM-FG Dacron graft delivery may be useful in preventing local infection by enhancing the delivery of VCM to the local areas of the implanted site in rats.

Animals↗
PubMed1997

2.1 kb 5'-flanking region of the brain type dystrophin gene directs the expression of lacZ in the cerebral cortex, but not in the hippocampus.

Duchenne muscular dystrophy is a muscle-wasting disease accompanied by a variable, but often significant degree of mental retardation, possibly due to the absence of dystrophin. However, the function of brain type dystrophin remains insufficiently clear. With this background, in order to study the cell-specific regulation of brain type dystrophin expression in mice, we generated transgenic mice carrying the 2.1 kb 5'-fragment of the mouse brain type dystrophin gene, fused to the coding region of the bacterial lacZ gene. Three transgenic mice lines showed lacZ expression in the cerebral cortex. However, lacZ expression was not detected in the CA region of the hippocampus. These results suggest that the 2.1 kb 5'-fragment of the mouse brain type dystrophin gene contains the regulatory element required for its expression in the cerebral cortex, but not in the hippocampus.

Animals↗
PubMed1997

Targeted integration of DNA using mutant lox sites in embryonic stem cells.

Site-directed DNA integration has been achieved by using a pair of mutant lox sites, a right element (RE) mutant lox site and a left element (LE) mutant lox site [Albertet al. (1995)Plant J., 7, 649-659], in mouse embryonic stem (ES) cells. We established ES cell lines carrying a single copy of the wild-type lox Por LE mutant lox site as a target and examined the frequency of site-specific integration of a targeting vector carrying a loxP or RE mutant lox site induced by Cre transient expression. Since our targeting vector contains a complete neo gene, random integrants can form colonies as in the case of a gene targeting event through homologous recombination. With our system, the frequency of site-specific integration via the mutant lox sites reached a maximum of 16%. In contrast, the wild-type loxP sites yielded very low frequencies (<0.5%) of site-specific integration events. This mutatedloxsystem will be useful for 'knock-in' integration of DNA in ES cells.

Animals↗
PubMed1997

Comparison of amyloid deposition in two lines of transgenic mouse that model familial amyloidotic polyneuropathy, type I.

We previously produced a transgenic mouse line designated MT-hMet30 by introducing the human mutant transthyretin (TTR) gene carrying the mouse metallothionein promoter, and showed that the presence of human variant TTR is sufficient for amyloid deposition in various tissues of these transgenic mice. However, the expression pattern of human mutant transthyretin gene in the mouse was different from that in man. To analyse pathologic processes, it is essential to establish a transgenic mouse line in which the development and tissue-specific expression of the human mutant TTR gene is the same as in man. Thus, we produced two additional transgenic mouse lines carrying the human mutant TTR gene containing either 0.6 kb (0.6-hMet30) or 6.0 kb (6.0- hMet30) of the upstream region. The expression levels of 6.0-hMet 30 gene in the liver and serum were the same as in man and about 10 times higher than those of 0.6-hMet30 gene in the liver and serum were the same as similar tissues to human patients except for the peripheral and autonomic nervous tissues. The amyloid deposition started earlier and was more extensive in 6.0-hMet30 than 0.6-hMet30 mice, suggesting that the serum levels of human mutant TTR are correlated with the occurrence and degree of amyloid deposition, to some extent. Neither amyloid deposition nor degenerative changes were observed in the peripheral and autonomic nervous systems despite the transgene expression in the choroid plexus of the 6.0-hMet30 mice. In the 6.0-hMet30 mice, amyloid deposition started at 9 months of age, although the serum level of human mutant TTR reached the adult level at 1 month. These results suggest that intrinsic environmental factors other than the mutant gene are involved in the late-onset deposition of amyloid fibrils. Transgenic mice described here should be useful for analysing such factors.

Age Factors↗
PubMed1997

Molecular properties of the proteasome activator PA28 family proteins and gamma-interferon regulation.

BACKGROUND: Recent cDNA cloning of two homologous proteasome activators, PA28 alpha and PA28 beta, indicated the presence of a structurally related third protein, Ki antigen, but a functional relationship between Ki antigen and the two PA28 proteins is unknown. Accumulating evidence has implicated an important role for PA28 in the major histocompatibility complex (MHC) class I-restricted antigen processing pathway. Recently, an immunomodulatory cytokine gamma-interferon (gamma-IFN) was found to increase greatly the messages for PA28 alpha and PA28 beta, but not Ki antigen, in human cells. RESULTS: Ki antigen was co-immunoprecipitated with the 20S proteasome by anti-proteasome antibody, and associated reversibly with the 20S proteasome, as observed for PA28 alpha and PA28 beta. Therefore, Ki antigen was renamed PA28 gamma. Anti-PA28 gamma antibody, however, did not immunoprecipitate PA28 alpha and PA28 beta. gamma-IFN caused an almost complete loss of the PA28 gamma protein in cells without affecting its mRNA level, whereas the levels of both mRNA and protein for PA28 alpha and PA28 beta were coordinately upregulated by gamma-IFN. Finally we showed that the human chromosomal genes of PA28 alpha and PA28 gamma were located on 14q11.2 and 17q21.32-21.33, respectively. CONCLUSION: PA28 gamma (equivalent to Ki antigen) is a new member of the PA28 family proteins. It exists as a unique homopolymer under non-denaturing conditions. gamma-IFN was found to induce the expression of PA28 alpha and PA28 beta, whereas it caused almost complete loss of the PA28 gamma protein in cells. The reciprocal expression of the PA28 family proteins may imply their involvement in distinct biological processes.

Amino Acid Sequence↗
PubMed1997

Lymphohaematopoietic abnormalities and systemic lymphoproliferative disorder in interleukin-2 receptor gamma chain-deficient mice.

Interleukin-2 (IL-2) receptor gamma chain-deficient mice with a truncated mutation showed the absence or severe reduction of natural killer cells, decreased numbers of T- and B-cells, marked hypoplasia of the thymus and peripheral lymphoid tissues, defective formation of lymphoid follicles and germinal centre in the peripheral lymphoid tissues, and the absence of Peyer's patches in the intestinal mucosa. In addition, marked splenomegaly with extramedullary haematopoiesis, increased level of IgM and decreased levels of IgG and IgE in serum, severe reduction of conventional B cells (B-2) in the peripheral lymphoid tissues, the presence of IgM-producing CD5+ B cells (B-1) and their differentiation into plasma cells and Motto cells in the spleen, and increased production and differentiation of macrophages in various tissues were found in the mutant mice. However, the development of both marginal metallophilic macrophage populations in the spleen and of their related macrophages in the other tissues of the mutant mice was severely impaired. All these abnormalities seem to be induced by the loss-of-function of the IL-2 receptor gamma chain. From 8 weeks of age on, inflammatory changes occurred in the intestines, mesenteric lymph nodes, lungs, liver, and kidneys of the mutant mice. Besides the absence of Hassall's corpuscles, thymic cysts were frequently observed in the mutant mice. These pathological abnormalities suggest that the gamma chain is implicated not only in lymphoid and haematopoietic development but also in thymic epithelial cell ontogeny.

Animals↗
PubMed1997

A 900 bp genomic region from the mouse dystrophin promoter directs lacZ reporter expression only to the right heart of transgenic mice.

In order to study the regulatory mechanism of developmental and tissue-specific expression of the muscle type dystrophin gene in mice, transgenic mice were generated carrying the 900 bp genomic fragment derived from the muscle type dystrophin promoter region fused to the bacterial lacZ gene. Six independent transgenic mouse lines showed specific reporter gene expression in the right heart, but not in skeletal or smooth muscle. The reporter gene expression was first detected in the presumptive right ventricle of the embryos at 8.5 days post coitum and the expression continued only in the right ventricle throughout the development and at the adult stage. The results indicate that the 900 bp genomic fragment contains the regulatory element required for expression of dystrophin only in the right heart, suggesting that distinct elements are responsible for the expression in the left and right compartments of the heart, and/or in skeletal and smooth muscle cells. Based on these findings, the relationship between defects in muscle type promoter and the diseases caused by abnormal dystrophin expression is discussed.

Animals↗
PubMed1997

Efficiency of recombination by Cre transient expression in embryonic stem cells: comparison of various promoters.

The Cre-loxP recombination system of bacteriophage P1 is frequently utilized in genetic manipulation in embryonic stem (ES) cells. The level of Cre expression is critical to induce loxP site-specific recombination in ES cells. To compare the efficiency of recombination, we constructed four Cre expression vectors driven by different promoters: cytomegarovirus/chicken beta-actin (CAG) promoter, human polypeptide chain elongation factor 1alpha (hEF-1alpha) promoter, mouse phosphoglycerate kinase-1 (mPGK) promoter, and polyoma enhancer/herpes simplex virus thymidine kinase (MC1) promoter. We introduced these Cre expression vectors by electroporation into three ES cell lines carrying a single copy of CAG-loxP-chloramphenicol acetyltransferase (CAT) gene-loxP-beta-galactosidase (beta-gal) gene construct. Since the Cre-mediated recombination leads to excision of the CAT gene, the efficiency of recombination can be monitored as beta-gal expression. No selection system was used in the experiments. The maximum recombination frequency was obtained when the CAG promoter was used, followed by the hEF-1alpha promoter, the mPGK promoter and the MC1 promoter in order. These results indicate that the efficiency of recombination in transient expression system correlates with the promoter activity of Cre expression vector. Thus, it is important to choose the promoter for effective recombination by Cre.

Actins↗
PubMed1997

Ocular membrane permeability of hydrophilic drugs for ocular peptide delivery.

The purpose of this study is to investigate the ocular membrane permeability and the permeation mechanism of hydrophilic drugs such as thyrotropin-releasing hormone (TRH), p-nitrophenyl beta-cellopentaoside (PNP) and luteinizing hormone-releasing hormone (LHRH). The penetration of hydrophilic drugs was measured across the isolated corneal and conjunctival membranes of albino rabbits using a two-chamber diffusion glass cell. The corneal permeabilities of hydrophilic drugs were much lower than those of beta blockers reported previously. The corneal penetration of TRH was the highest among the hydrophilic drugs studied. Scraping the corneal epithelium increased the penetration of hydrophilic drugs. Conjunctival membranes showed higher permeability to hydrophilic drugs compared with corneal membranes. The permeability of drugs was also analysed by Fick's equation. The partition parameter and diffusion parameter of TRH, PNP and LHRH in the cornea were lower than those in scraped cornea and conjunctiva. In addition to the data of fluorescein isothiocyanate-dextran reported previously, the permeability coefficient of hydrophilic drugs through the cornea, scraped cornea and conjunctiva correlated with molecular weight of the drugs. The diffusion parameters of hydrophilic drugs decreased with an increase of molecular weight for all ocular membranes. The extent of dependency of partition parameters on the molecular weights of drugs varied according to the ocular membrane. These results indicate that ocular membranes are sufficiently different in permeation character and mechanism to control the extent and pathway for ocular absorption of hydrophilic drugs.

Animals↗
PubMed1997

In-situ ocular absorption of ophthalmic beta-blockers through ocular membranes in albino rabbits.

Ocular membranes have been characterized by in-situ absorption of the ophthalmic beta-blockers carteolol (hydrophilic) and timolol and befunolol (lipophilic) using a cylindrical cell. After introduction of drug solution into the cell on the cornea, sclera (bulbar conjunctival and scleral layer) or palpebral conjunctiva, the disappearance of the drug from the cell was determined as in-situ absorption. The ophthalmic drugs disappeared from the conjunctival and scleral membranes although disappearance from the cornea was hardly observed. The conjunctival membrane showed the highest permeability. Lipophilic drugs were more permeable than hydrophilic. In-situ apparent permeability coefficients of the ophthalmic drugs through the conjunctiva and sclera correlated with the lipophilicity of drugs. A high drug concentration in the aqueous humor was observed after corneal application. There is a relationship between concentration in the aqueous humor was observed after corneal application. There is a relationship between concentrations of drugs in the aqueous humor and previously reported in-vitro apparent permeability coefficients of the drugs in the cornea. This in-situ method using a cylindrical cell is a useful method of investigating the ocular absorption of ophthalmic drugs.

Absorption↗
PubMed1997

An electrophysiological study of the effects of acute methylmercury chloride exposure on the function of the guinea pig cochlea.

The inner ear function of methylmercury chloride (MMC)-exposed guinea-pigs was examined in this study. Previous studies which investigated the function of the eighth cranial nerve and Corti-organ using cochlear microphonics (CM), compound action potential (CAP) and measurement of endocochlear potential (EP) reported ototoxicity following experimental exposure to MMC. In this report, the effect of MMC on the cochlea and the eighth cranial nerve were investigated systematically by measuring CM, action potential (AP), EP and K+ ion concentration of the endolymph. Guinea-pigs were injected with 5 mg/kg MMC (using 0.2% solution) twice a week for 1-3 weeks. The maximum output voltage of AP was decreased by injection of MMC (5 mg/kg x 6). A decrease in the CM maximum output voltage and the elevation of CM pseudothreshold was seen after MMC injection. Changes in EP during 3 min anoxia were observed, especially a decrease in the absolute value of the negative potential. The endolymph K+ ion concentration remained unchanged. These findings indicate that the diffusion potentials decreased and at the same time was reduced the maximum output voltage in CM induced by MMC injection (5 mg/kg x 6) in this experiment.

Action Potentials↗
PubMed1997

Analysis of amyloid deposition in a transgenic mouse model of homozygous familial amyloidotic polyneuropathy.

Amyloid fibrils derived from the Japanese, Portuguese, and Swedish types of familial amyloidotic polyneuropathy all consist of a variant transthyretin (TTR) with a substitution of methionine for valine at position 30 (TTR Met 30). In an attempt to establish an animal model of TTR Met-30-associated homozygous familial amyloidotic polyneuropathy and to study the structural and functional properties of human TTR Met 30, we generated a mouse line carrying a null mutation at the endogenous ttr locus (ttr-/-) and the human mutant ttr gene (6.0-hMet 30) as a transgene. In these mice, human TTR Met-30-derived amyloid deposits were first observed in the esophagus and stomach when the mice were 11 months of age. With advancing age, amyloid deposits extended to various other tissues. Because no significant difference was detected in the onset, progression, and tissue distribution of amyloid deposition between the ttr-/- and ttr+/+ transgenic mice expressing 6.0-hMet 30, endogenous normal mouse TTR probably does not affect the deposition of human TTR Met-30-derived amyloid in mice. TTR is a tetramer composed of four identical subunits that binds thyroxine (T4) and plasma retinol-binding protein. The introduction of 6.0-hMet 30 into the ttr-/- mice significantly increased their depressed serum levels of T4 and retinol-binding protein, suggesting that human TTR Met 30 binds T4 and retinol-binding protein in vivo. The T4-binding ability of human TTR Met 30 was confirmed by the analysis of T4-binding proteins in the sera of ttr-/- transgenic mice expressing 6.0-hMet 30. The T4-binding studies also demonstrated the presence of hybrid tetramers between mouse and human TTR subunits in the ttr+/+ transgenic mice expressing 6.0-hMet 30.

Amyloid↗
PubMed1997

[A case of Morgagni hernia composed of hypertrophic adipose tissue in the falciform ligament].

We report our recent experience with an asymptomatic case of Morgagni hernia composed of hypertrophic adipose tissue in the falciform ligament. The patient was a 47-year-old obese para-II woman. A chest X-ray during a routine health checkup showed an abnormal shadow in the right cardiophrenic angle that was larger than one year previously. Computed tomograms revealed a fat-density mass in the right side of the chest in contact with the anterior chest wall, pericardium and sternum that continued into the abdominal cavity. Magnetic resonance imaging (MRI) showed that the intrathoracic mass lesion was continuous with the subphrenic tissue, and that the hilus of the hernia was 5 x 3 cm in size. A barium gastro-intestinal series revealed no abnormal findings. Surgical repair was achieved through the transabdominal approach. The omentum was found in its normal position. The herniated adipose tissue in the falciform ligament was repositioned on the peritoneal side, and excised. The hilus of the hernia was then closed with knotted sutures. Postoperatively, the abnormal shadow on the X-ray was no longer present, and the postoperative course was uneventful. Histological examination revealed the hernia to consist of mature adipose tissue 5 x 10 x 3 cm in size. This is the first case of Morgagni hernia composed of hypertrophic adipose tissue in the falciform ligament reported in Japan.

Adipose Tissue↗
PubMed1997

The role of E-selectin for neutrophil activation and tumor metastasis in vivo.

The selectin class of adhesion molecules plays a critical role in facilitating leukocyte adhesion to and subsequent transmigration of endothelium. On this basis, selectins have been suggested to promote metastasis of certain types of tumors, although direct evidence is lacking. To explore this hypothesis two sets of transgenic mice were developed, one TgNES, which constitutively expresses cell surface E-selectin in all tissues, the other TgNEsol, which expresses truncated, soluble E-selectin in the liver. Both transgenic mice showed apparently normal phenotype. However in TgNES mice, but not in TgNEsol mice, the number of neutrophil decreased to 50% compared with that in their negative littermate. And also these neutrophils were markedly activated. On the other hand, B16 F10 melanoma cells were stably transfected with alpha 1-3/4 fucosyltransferase-specific cDNA (B16F10 ft), allowing them to express E-selectin ligands. Normal mice injected with B16F10 ft developed lung tumors exclusively. In contrast, TgNES mice developed massive, infiltrating liver tumors. TgNEsol mice also developed liver tumors that grow more slowly. These observations suggest the important role of E-selectin for neutrophil activation and tumor metastasis in vivo.

Actins↗
PubMed1996

TNF-alpha gene expression in the liver of the IFN-gamma transgenic mouse with chronic active hepatitis.

Cytokine gene expression in the liver of transgenic mouse which specifically expresses interferon-gamma gene (IFN-gamma) was measured using polymerase chain reaction analysis. IFN-gamma mRNA was found to be expressed in the transgenic mouse liver along with TNF-alpha mRNA. Messenger RNAs of CD4 and CD8, maturation markers of T cells, were expressed in both normal and transgenic mouse livers, indicating the presence of resident T cells. The level of CD4 and CD8 expression was slightly elevated in the transgenic mouse case, indicating an increased number of CD4+ and/or CD8+ T cells, but the lack of the activation marker IL-2 mRNA suggested a nonactivated state. TGF-beta 1 mRNA was expressed in both normal and transgenic mouse livers without any increase in the latter, and therefore does not appear to be involved in the development of chronic active hepatitis in this transgenic mouse. Since TNF-alpha is a terminal mediator of liver injury in several animal liver injury models, its high expression, presumably a result of the IFN-gamma which is transcribed from the introduced gene, might be involved in the development of chronic active hepatitis in this transgenic mouse.

Alanine Transaminase↗