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Biomedical subjects

K Yamamura

Publications and source records attributed to K Yamamura.

At least 217 records · Page 12Linked to original sources
PubMed1991

Development of two types of hepatocellular carcinoma in transgenic mice carrying the SV40 large T-antigen gene.

We produced transgenic mice by introducing a fusion gene (ST) comprising of the promoter for human serum amyloid P component (SAP) and the coding region of the simian virus 40 (SV40) large tumor antigen (Tag). The ST transgenic mice developed hepatocellular carcinomas (HCC) between 7 and 12 weeks of age. Clinically and pathologically these HCC were classified into two types: diffuse and focal. In the diffuse type Tag is expressed in almost all hepatocytes and HCC has presumably developed from these T-antigen-positive cells. The focal type, which resembles human HCC, is only Tag positive in the neoplastic nodules. These are surrounded by Tag-negative normal hepatocytes that form normal lobular structures. As the human SAP promoter can direct adult liver-specific expression of heterologous genes, it is assumed that Tag gene expression in the transgenic animals is increased sharply after birth. Interestingly, a similar level of Tag expression was observed in both the cytoplasm and the nucleus. Our results suggest that spatial differences in Tag expression result in the generation of two types of HCC in transgenic mice and that the ST mouse can serve as a model for human hepatocarcinogenesis.

Alanine Transaminase↗
PubMed1991

(BALB/c x C57BL/6)F1 mice are tolerant to undetectable mixed haplotype A beta dA alpha b and mixed isotype A beta dE alpha d self class II molecules.

The existence of mixed haplotype A beta dA alpha b and mixed isotype A beta dE alpha d molecules was demonstrated in A beta d gene introduced C57BL/6 (B6) transgenic and in A beta dE alpha d double gene introduced B6 transgenic mice, respectively. Using alloreactive and antigen reactive T-cell clones, these mixed class II molecules were shown to function as mixed lymphocyte culture reaction (MLR) stimulating determinants and restriction elements for antigen recognition by T cells. The amounts of expression of these mixed class II molecules were sufficient for the stimulation of alloreactive T cells in primary MLR culture. (BALB/c x B6)F1 (CBF1) mice were shown not to express functional mixed haplotype and mixed isotype class II molecules using alloreactive and antigen reactive T-cell clones. Interestingly, however, CBF1 mice did not respond to such mixed haplotype and mixed isotype class II molecules. These results show that CBF1 mice do not respond to undetectably-expressed class II molecule and suggest that they are tolerant to undetectable self class II molecules. The possible interpretations for this are discussed.

Animals↗
PubMed1991

Increase of sialylated tetraantennary sugar chains in parallel to the higher lung-colonizing abilities of mouse melanoma clones.

The N-linked sugar chains of melanoma cell membrane from five murine B16 melanoma clones (F1, F10, BL6, W1-4, and C4-1) with different degrees of metastatic abilities after intravenous and intrafootpad injections were released quantitatively as oligosaccharides by hydrazinolysis, and their structures were analyzed by serial lectin column chromatography, Bio-Gel P-4 column chromatography, and sequential glycosidase digestion. Sugar chain structures of each clone have shown to consist of the same elemental oligosaccharides, but to differ in their percent compositions. More than 84% of the neutral oligosaccharides were high mannose-type sugar chains. Most complex-type sugar chains were sialylated, of which the major structure was tetraantennary sugar chain. Highly lung-colonizing F10 cells had 1.4 and 1.7 times more non-repeated tetraantennary sugar chains than moderately colonizing F1 and C4-1 cells, respectively, and 2.5 times more than poorly colonizing W1-4 cells. BL6 cells, which are also highly lung-colonizing, had 1.5 and 1.9 times more non-repeated tetraantennary sugar chains than F1 and C4-1 cells, respectively, and 2.8 times more than W1-4 cells. These results suggest that increase of sialylated tetraantennary complex-type sugar chains without N-acetyllactosamine repeating units of B16 melanoma cells might correlate with the higher lung-colonizing ability after intravenous injection.

Animals↗
PubMed1991

Production and effect of infectious Dane particles in transgenic mice.

We have demonstrated by immunoelectron microscopy that 42-nm particles with double-shelled structures characteristic of Dane particles are present in the serum of transgenic mice, 1.2HB-BS 10, carrying partly duplicated hepatitis B virus (HBV) genome. Furthermore, these particles were shown to infect primary human fetal hepatocytes as demonstrated by the elevation of HBV surface antigen (HBsAg) in the culture medium. HBV DNA is known to be expressed in a liver- and kidney-specific manner in the adult mouse, so we examined the developmental expression of viral antigens. In the liver, viral antigens (HBsAg and HBV e antigen) began to be expressed before birth and the level of expression showed a sharp rise after birth. On the other hand, in the kidney, viral antigens began to be expressed after birth. Serum levels of viral antigens were roughly proportional to the levels of expression in the liver, suggesting that the liver is the main source for viral antigens in the serum. None of these transgenic mice produced anti-HBs or anti-HBV core response or showed biochemical or pathological change up to at least 24 months of age. All these results suggest that infectious viral particles can be produced in transgenic mice, and that expression and replication of HBV DNA are not toxic in vivo.

Aging↗
PubMed1991

[A case of remarkable effect of clindamycin in nasal septum abscess caused by Streptococcus milleri].

We encountered a 14-year-old male patient with a destructive abscess of nasal septum, caused by Streptococcus milleri. He was successfully treated with Clindamycin in combination with surgical intervention. We emphasized the significance of Streptococcus milleri as a causative agent for abscess formation, and clindamycin should be considered as a first choice of antibiotics against Streptococcus milleri infection.

Abscess↗
PubMed1991

Role of serum amyloid P component for systemic amyloidosis in transgenic mice carrying human mutant transthyretin gene.

The role of serum amyloid P component (SAP) for systemic amyloidosis in a transgenic mouse model for an autosomal dominant disease, familial amyloidotic polyneuropathy (FAP), was examined. For this purpose, two lines of transgenic mouse were produced by introducing the human mutant transthyretin (TTR) gene and the human SAP gene, respectively. Two lines of transgenic mice were mated to produce double transgenic mice carrying both human mutant TTR gene and human SAP gene. The serum concentration of human SAP in these transgenic mice was about 42 micrograms/ml and was about equal to that in human control serum. In case of single transgenic mice carrying human mutant TTR gene, amyloid deposition starts at around 6 months of age, and the amount of amyloid deposition increases gradually with age. Amyloid deposition is observed in many tissues including heart, kidney and thyroid gland, where amyloid deposition is commonly observed in FAP patients. In double transgenic mice, onset, progression and tissue distribution of amyloid deposition were the same as those in single transgenic mouse. These results clearly suggest that SAP is not important for the initiation and progression of amyloid deposition.

Age Factors↗
PubMed1991

Effects of 250 and 500 Hz tone exposure on the inner ear of guinea pigs as determined by electrophysiological techniques.

The electrophysiological study of cochlear microphonics (CM), whole nerve action potential (AP) and endocochlear potential (EP) were examined. (1) With the extension of the exposure time of 500 Hz tone, a decrease of CM maximum output voltage in test frequency from 2 to 6 kHz was observed. (2) N1 potential of AP decreased very significantly by 500 Hz tone exposure. (3) A very pronounced decrease of the absolute value of the negative potential of the EP in 500 Hz exposure was seen.

Action Potentials↗
PubMed1991

[A case showing the infraoptic course of the anterior cerebral artery associated with anterior cerebral artery aneurysm].

A ruptured anterior cerebral artery aneurysm with anomalous right infraoptic course of the anterior cerebral artery (ACA) was reported. A 40-year old male was admitted because of SAH episode, and computerized tomography (CT) on the day of admission revealed hemorrhage in both Sylvian and interhemispheric fissures. Four-vessel angiography was performed on the same day. A saccular aneurysm was demonstrated in the region of the anterior communicating artery (ACoA), and anomalous artery, which originated from the intradural right carotid artery at the level of the right ophthalmic artery was found to be running medially and superiorly. It supplied the bilateral callosomarginal arteries and the unpaired pericallosal artery. The fenestration of the vertebral artery, duplication of bilateral superior cerebellar arteries, and an occipital artery arising from the right internal carotid artery at the C3 level were found. Surgery was performed on the first day of admission, and the anterior interhemispheric approach was selected. The anomalous branch of the right ICA ran beneath the right optic nerve, ascended between the optic nerves, and supplied the ACoA system. The left hypoplastic A1 segment entered the ACoA. However, the right A1 segment could not be found. The aneurysmal neck, situated between the bilateral callosomarginal arteries and the unpaired pericallosal artery, was clipped with Sugitas curved clip. The postoperative course was uneventful and a follow-up angiograph revealed successful obliteration of the aneurysm.

Adult↗
PubMed1991

Systemic amyloidosis in transgenic mice carrying the human mutant transthyretin (Met30) gene. Pathologic similarity to human familial amyloidotic polyneuropathy, type I.

To analyze the pathologic processes of amyloid deposition in type I familial amyloidotic polyneuropathy (FAP), mice were made transgenic by introducing the human mutant transthyretin (TTR) gene. In these transgenic mice, amyloid deposition started in the gastrointestinal tract, cardiovascular system, and kidneys 6 months after birth and extended to various other organs and tissues with advancing age. At age 24 months, the pattern of amyloid deposition was similar to that observed in human autopsy cases of FAP, except for its absence in the choroid plexus and in the peripheral and autonomic nervous systems. Amyloid deposition was shown to be composed of human mutant TTR and, in addition, mouse serum amyloid P component. These results clearly indicate that human variant TTR produced in transgenic mice deposits is a major component of amyloid fibrils in various organs and tissues. Thus this animal model is useful for analyzing how amyloid deposition initiates and proceeds in FAP.

Amyloid↗
PubMed1990

Tissue-specific expression of rat pyruvate kinase L/chloramphenicol acetyltransferase fusion gene in transgenic mice and its regulation by diet and insulin.

We produced transgenic mice carrying about 3 kb of the 5'-flanking sequence of the rat pyruvate kinase L gene linked to the chloramphenicol acetyltransferase (CAT) structural gene. Expression of the transgene was observed only in tissues in which the endogenous L-type pyruvate kinase is expressed. Dietary glucose or insulin induced similar increases in the levels of CAT and L-type pyruvate kinase mRNAs in the liver. However, the fructose-induced level of CAT mRNA was about 3- and 6- fold lower than those of endogenous L-type pyruvate kinase mRNA in the liver and kidney, respectively, confirming our previous finding that stabilization of the transcripts of the pyruvate kinase L gene is an important regulatory step in fructose induction, especially in the kidney. Thus we conclude that all the cis-acting elements responsible for tissue-specific expression of the L-type pyruvate kinase and its stimulation by dietary components and insulin are localized in the sequence from about nucleotide -3000 to +37 in the pyruvate kinase L gene.

Animals↗
PubMed1990

Direct evidence for the contribution of the unique I-ANOD to the development of insulitis in non-obese diabetic mice.

Insulin-dependent diabetes mellitus is characterized by the infiltration of lymphocytes into the islets of Langerhans of the pancreas (insulitis) followed by destruction of insulin-secreting beta-cells leading to overt diabetes. The best model for the disease is the non-obese diabetic (NOD) mouse. Two unusual features of the class II major histocompatibility complex (MHC) of the NOD mouse are the absence of I-E and the presence of unique I-A molecules (I-ANOD), in which aspartic acid at position 57 of the beta-chain is replaced by serine. This feature is also found in the HLA-DQ chain of many Caucasians with insulin-dependent diabetes mellitus. We have previously reported that the expression of I-E prevents the development of insulitis in NOD mouse. Here we report that the expression of I-Ak (A alpha kA beta k) in transgenic NOD mice can also prevent insulitis, and that this protection is seen not only when the I-A beta-chain has aspartic acid as residue 57, but also when this residue is serine. These results show that the single amino-acid substitution at position 57 of the I-A beta-chain from aspartic acid to serine is not sufficient for the development of the disease.

Animals↗
PubMed1990

Electrophysiological determinations of the effects of 1 kHz noise exposure on the high-frequency hearing of guinea pigs.

The effects of noise were studied in 90 5-week-old albino Hartley guinea pigs with normal hearing. The following experimental setup was used: (1) exposure to 1 kHz tones at 100 dB for 4 h, 20 h and 40 h; (2) exposure to 1 kHz tones at 110 dB for 20 h and 40 h. In order to investigate the effects of the noise exposures on the hearing of the guinea pigs, cochlear microphonics (CM), whole nerve action potentials (AP) and endocochlear potentials (EP) were examined. We obtained the following results. With a high sound pressure, a decrease was observed in the CM maximum output voltage in the test frequencies from 2 kHz to 6 kHz while the CM threshold increased ("pseudo threshold"). Intensity function of the N1 potential of the AP using a 7 kHz tone burst decreased; the threshold of the N1 potential also increased considerably by exposure to chronic high sound pressure. An extension of latency and a decrease in the absolute value of the negative potential in EP were induced by chronic noise exposure.

Animals↗
PubMed1990

HBV production in transgenic mice.

We produced transgenic mice by microinjecting a partially duplicated copies of hepatitis B virus (HBV) gene into fertilized eggs of C57BL/6 mice. One mouse was a high producer of HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) in the serum. All offspring carrying HBV DNA were positive for both antigens in the serum. The HBV DNA was expressed in liver- and kidney-specific manner. The normal process of HBV replication, including the packaging of the pregenome 3.5-kb RNA into a nucleocapsid, the reverse-transcription of the complete minus strand DNA, and the release of Dane particles into the serum before the completion of synthesis of plus strand, occurred in the liver of these transgenic mice. These results suggest that the species specificity of HBV infection is not due to the inability to replicate in nonnatural host but to the lack of receptors or factors needed for virus adsorption and internalization. The founder mouse is now 19 months of age but shows no clinical or pathological change, suggesting that HBV itself is not cytopathic.

Animals↗
PubMed1990

Antigen dynamics in melanocytic and nevocytic melanoma oncogenesis: anti-ganglioside and anti-ras p21 antibodies as markers of tumor progression.

Based on melanoma pathogenesis, phenotypic dynamics in pigment cell tumor progression detected with 11 MoAb have been defined. Anti-melanosomal A4F11 antibody reacts with every type of pigment cell tumor tested except for a few specimens. TNKH1 and anti-K.1.2 antibodies recognize nevocytic benign to premalignant tumors. HLA-DR, A.1.43, and A.10.33 antigens are expressed in advanced melanomas. Staining with anti-ganglioside GM3 and GD3 antibodies, M2590 and 4.2, respectively, reveals that most pigment cell tumors express gangliosides GM3 and GD3. But A2B5 antibody, which detects some polysialogangliosides such as GQ1C, reacts with highly progressed melanoma cells. Anti-ras p21 antibodies, RASK-3 and RASK-4, react with malignant melanomas and their premalignant lesions. These findings suggest the following: A4F11 is a universal marker of pigment cell tumors. TNKH1 and anti-K.1.2 antibodies might not be markers of melanocytic tumors but of nevocytic benign to premalignant tumors. Melanoma cells express gangliosides GM3 and GD3 as common pigment cell antigens and synthesize aberrant polysialogangliosides. Anti-ganglioside MoAb, including A2B5, are possible markers of the level of malignancy in melanoma cells like anti-A.1.43 and anti-A.10.33 antibodies. Enhanced ras p21 expression already appears on premalignant pigment cells.

Antibodies, Monoclonal↗
PubMed1990

Correlation of tissue-specific methylation with gene inactivity in hepatitis B virus transgenic mice.

We produced transgenic mice using two constructs, HB-GII and 1.2HB-BS, of hepatitis B virus (HBV) DNA. The former has been designed to express mRNAs for HBV surface antigen (HBsAg), and the later to express all mRNAs of HBV. Several lines of the transgenic mice carrying each construct were examined for the tissue-specificity and level of HBV DNA expression, and for the relationship between expression and methylation of the transgenes. Only one out of ten for HB-GII and one out of eight for 1.2HB-BS were high producers of viral antigens. In high producers, transgenes were expressed in the liver and the kidneys. But in low producers, transgenes were usually expressed only in the kidneys. There is a reciprocal relationship between the level of expression and the degree of methylation, that is, the higher the level of expression, the less the degree of methylation. We also observed that the expression of the integrated HBV-DNA was repressed by methylation following its passage through the female germline in one line. Thus, in addition to transacting factors that can control the gene expression positively or negatively, this tissue-specific methylation may also be involved in the regulation of HBV gene expression.

Animals↗
PubMed1990

Establishment of a pancreatic beta cell line that retains glucose-inducible insulin secretion: special reference to expression of glucose transporter isoforms.

Two cell lines have been established from insulinomas obtained by targeted expression of the simian virus 40 T antigen gene in transgenic mice. These cell lines, designated MIN6 and MIN7, produce insulin and T antigen and have morphological characteristics of pancreatic beta cells. MIN6 cells exhibit glucose-inducible insulin secretion comparable with cultured normal mouse islet cells, whereas MIN7 cells do not. Both cell lines produce liver-type glucose transporter (GT) mRNA at high level. Brain-type GT mRNA is also present at considerable level in MIN7 cells, but is barely detectable in MIN6 cells, suggesting that exclusive expression of the liver-type GT is related to glucose-inducible insulin secretion. MIN6 cells do not express either major histocompatibility (MHC) class I or class II antigens on the cell surface. However, treatment with interferon-gamma induces high levels of MHC class I antigens, and a combination of interferon-gamma and tumor necrosis factor-alpha induces a MHC class II antigen on the cell surface. These results emphasize that the MIN6 cell line retains physiological characteristics of normal beta cells. The MIN6 cell line will be especially useful to analyze the molecular mechanisms by which beta cells regulate insulin secretion in response to extracellular glucose concentrations. We discuss a possible role of GT isoforms in glucose sensing by beta cells.

Animals↗