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Biomedical subjects

N Kono

Publications and source records attributed to N Kono.

At least 109 records · Page 6Linked to original sources
PubMed1991

Animal model of systemic carnitine deficiency: analysis in C3H-H-2 degrees strain of mouse associated with juvenile visceral steatosis.

We analyzed carnitine profiles in C3H-H-2 degrees strain of mouse associated with fatty liver, hyperammonemia and hypoglycemia (Koizumi et al., 1988). Carnitine levels in serum, liver and muscle of mouse with fatty liver were markedly decreased in comparison with those of control mouse (littermates without fatty liver). This is a useful animal model to analyze the role of carnitine in lipid, amino acid and carbohydrate metabolism.

Aging↗
PubMed1991

HLA-DQA1*1 contributes to resistance and A1*3 confers susceptibility to type 1 (insulin-dependent) diabetes mellitus in Japanese subjects.

In this study HLA-DQA1 and TNF genes in addition to HLA-DQB1 gene were investigated at DNA level for elucidation of the genetic backgrounds of Type 1 (insulin-dependent) diabetes mellitus in Japanese subjects. DNA, amplified by polymerase chain reaction, was subjected to allele specific oligonucleotide dot blot analysis, restriction fragment length polymorphism analysis or DNA sequencing. Polymorphism of the TNF gene to NcoI did not correlate with Type 1 diabetes in Japanese patients. DQw1.2 had a protective effect against the disease, the DQA1*1 allele was significantly decreased and DQA1*3 allele was significantly increased. Seventeen out of twenty-two Type 1 diabetic patients (77%) were homozygous for DQA1*3 and five out of twenty-two (23%) heterozygous. The DQA1*3 gene of Type 1 diabetic patients had a normal nucleotide sequence. Furthermore, DQA1*3 was found unexpectedly in two patients without DR4 or DR9. These data indicate that DQA1 gene confers susceptibility and resistance to Type 1 diabetes in Japanese subjects.

Alleles↗
PubMed1991

Interactions between epithelial and mesenchymal cells in intrahepatic peribiliary glands in normal and hepatolithiatic livers.

The anatomy and pathology of the intrahepatic peribiliary glands were evaluated. In this study, we ultrastructuraly examined the peribiliary glands of normal and hepatolithiatic livers using common and serial ultrathin section observations. It is well known that these glands proliferate markedly in hepatolithiasis. These glands were composed of several acini surrounded by thickened and multilayered basement membranes, and there were mesenchymal cells (the majority were fibroblasts) in the periacinar fibrous connective tissue. Some cytoplasmic processes of acinar epithelial cells and mesenchymal cells in the periacinar connective tissue were in close contact with each other within the thickened and multilayered basement membranes. Such cell-to-cell interaction was most frequent in cases of hepatolithiasis, in which peribiliary glands proliferated markedly. In hepatolithiatic livers, some unmyelinated nerve fibers or axonal button profiles were in close contact with periacinar mesenchymal cells and also with cytoplasmic processes of glandular epithelial cells. Such contacts were rare in normal livers. These findings suggest that such epithelial and mesenchymal cell interactions and innervations play a part in the normal regulation of peribiliary glands and also in the proliferation of peribiliary glands in hepatolithiasis.

Adult↗
PubMed1991

Expression of HLA-DR antigens on interlobular bile ducts in primary biliary cirrhosis and other hepatobiliary diseases: an immunohistochemical study.

Using a monoclonal antibody to alpha chains of HLA-DR antigens, we found that damaged biliary epithelial cells in primary biliary cirrhosis (PBC) and, to a lesser degree and frequency, in other hepatobiliary diseases expressed HLA-DR antigens, while normal bile ducts did not. There was no correlation between biliary epithelial expression of HLA-DR antigens and intraepithelial migration of HLA-DR-positive cells. In PBC, HLA-DR antigens were strongly expressed on the damaged bile ducts surrounded by no or mild inflammatory cell infiltration (nonflorid duct lesion) and on those surrounded by intense lymphoid cells (florid duct lesion). Immunoelectron microscopy confirmed the presence of HLA-DR antigens on the cellular membranes of damaged biliary epithelial cells. Although expression of HLA-DR antigens on bile ducts may itself be a nonspecific epiphenomenon of damaged bile ducts, it seems possible in PBC that biliary epithelial cells are at first damaged in some way and express HLA-DR antigens (and probably self-antigens), and then fall victim to an autoimmune reaction characterized by marked lymphoid cell infiltration (florid duct lesions). The agent causing nonflorid duct lesions is unknown. The reasons why such expression does not lead to immunologic reactions in other hepatobiliary diseases are only speculative.

Antibodies, Monoclonal↗
PubMed1991

Two types of autoantibodies to adrenal medullary cells in type 1 (insulin-dependent) diabetic patients: prevalence, properties and implications.

Complement-fixing adrenal medullary antibodies were examined in sera from 170 (114 Type 1 and 56 Type 2) diabetic patients and normal subjects by indirect immunofluorescence methods. Two types of antibodies were detected; one showed a homogeneous immunofluorescence pattern (homogeneous-type) and the other a spotty pattern (spotty-type) in the cytoplasm of adrenal medullary cells. Both antibodies were IgG class and adrenal medulla-specific. The prevalence of the homogeneous-type was significantly higher in Type 1 diabetic patients with disease duration under 1 year (36%) than in those with duration of 1 year or more (1.1%), in Type 2 diabetic patients (1.8%) or in normal subjects (0%; P less than 0.01). Conversely, the prevalence of the spotty-type was not significantly different among all subjects examined (3.6-4.5%). The epitope for the homogeneous-type is likely to be a glycoconjugate since binding of this antibody was abolished after periodate oxidation. The epitope for spotty-type antibody is considered to be a peptide since it was trypsin sensitive. Patients who were positive for the homogeneous-type were also positive for islet cell antibodies, although their antibody titers were not correlated. We conclude that (1) adrenal medullary antibodies are of homogeneous-type or spotty-type and the antigenic determinants of these antibodies are different, and (2) the prevalence of the homogeneous-type is significantly higher in newly diagnosed Type 1 diabetic patients and its presence is associated with that of islet cell antibodies.

Adolescent↗
PubMed1991

Adenosine induces System A amino acid transport in cultured rat hepatocytes.

Adenosine caused a 2.5-fold increase in the sodium-dependent uptake of 2-aminoisobutyric acid in rat hepatocytes in primary culture following incubation for 3 h. The range of stimulating concentrations of adenosine corresponded to that of cAMP formation. Adenosine increased the Vmax of the transport without altering the Km for 2-aminoisobutyric acid. These effects of adenosine were abolished by actinomycin D. N6-L-Phenylisopropyladenosine also caused twofold increase in the amino acid transport. These findings suggest that adenosine induces System A amino acid transport in a transcription-dependent manner, and the P1-purinergic receptors are mainly involved in this action of the nucleoside.

Adenosine↗
PubMed1991

HLA-DP and susceptibility to insulin-dependent diabetes mellitus in Japanese.

Human leukocyte antigen (HLA) genes are candidates for susceptibility genes in insulin-dependent diabetes mellitus (IDDM). Recently, the association of DR and DQ with IDDM has been reported, but the role of HLA-DP genes remains uncertain. To address the question, we analyzed the DPB1 gene of 20 Japanese IDDM patients and 30 control subjects using a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis (PCR-RFLP method). DPB1*0501 was the most frequent allele both in Japanese patients and control subjects. There was no appreciable association between IDDM and the DPB1 allele in Japanese. The absence of association between IDDM and DP, in spite of the known association between this disease and both DR and DQ, suggests that the HLA locus (loci) telomeric to DP encodes susceptibility to IDDM.

Alleles↗
PubMed1991

Histological changes of the liver in experimental graft-versus-host disease across minor histocompatibility barriers. V. A light and electron microscopic study of the intralobular changes.

Intralobular changes of the liver in experimental graft-versus-host disease (GVHD) across minor histocompatibility barriers were investigated for up to 14 months after bone marrow transplantation. Sinusoidal lymphocyte infiltration, and necrosis and degeneration of hepatocytes were evident by day 4 and reached a maximum level at 2 weeks after transplantation, then gradually decreased, but they persisted during the entire period of observation, indicating that more or less hepatocyte injury may persist continuously in hepatic GVHD. Piecemeal necrosis was transiently observed around 2 weeks after transplantation, in parallel with the peak of lymphocyte infiltration into the portal area. Similarly, central vein endothelialitis (attachment of lymphocytes to endothelial cells) was transiently observed with a peak activity at 2 weeks after transplantation. Mild centrilobular and portal fibroplasia were evident by 2 weeks after transplantation, but they hardly progressed and no cases developed liver cirrhosis. Frequently lymphocytes were found located beneath endothelial cells and attached to hepatocytes. Ultrastructural observation revealed that sinusoidal lymphocytes were occasionally in contact with endothelial cells by means of cytoplasmic pseudopods. Also lymphocytes were frequently in close contact with hepatocyte plasma membranes over short distances. Lymphocytes occasionally accompanied other inflammatory cells, such as eosinophilic leukocytes and mononuclear phagocytic cells. Hepatocytes in close contact with lymphocyte and other inflammatory cells showed a varying degree of degenerative changes, including condensation of cytoplasm and nucleus with irregular nuclear contours, dilatation of endoplasmic reticulum and mitochondria, formation of cytoplasmic vacuoles, and loss of microvilli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Histological changes in the liver in experimental graft-versus-host disease across minor histocompatibility barriers. VI. A light and electron microscopic study of the periportal changes.

Periportal changes of the liver in experimental graft-versus-host disease (GVHD) across minor histocompatibility barriers were investigated electron-microscopically for up to 14 months after bone marrow transplantation (BMT). In GVHD mice, periportal changes affecting the limiting plate of hepatocytes were relatively mild and, in general, classical piecemeal necrosis was rarely observed. However, around 2 weeks after transplantation disruption of the limiting plate of hepatocytes was transiently observed. At that time, lymphocytes invaded directly into the hepatic parenchyma and were in close contact with hepatocytes mainly through a number of point-contacts of cell membranes. Hepatocytes in close contact with lymphocytes showed minor degenerative changes under electron microscopy. On the other hand, periportal bile ductules and canals of Hering were constantly injured by inflammatory cells during the entire observation period up to 14 months after BMT. They were abutted by lymphocytes, together with other inflammatory cells including eosinophils, neutrophils, plasma cells and monocytes. Infiltration of inflammatory cells into the epithelial layer of the bile ductules and canals of Hering through the basement membrane was frequently found. Inflammatory cells were in contact with duct epithelial cells mainly through a number of point-contacts of cell membranes. Epithelial cells in contact with inflammatory cells exhibited a number of degenerative changes, including condensation of cytoplasm, irregular contour of nucleus, dilatation of endoplasmic reticulum, formation of cytoplasmic vesicles, focal cytoplasmic degeneration, and so on.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Interferon-gamma inhibits thyroid-stimulating hormone-induced morphological changes and induces the expression of major histocompatibility complex class II antigen in thyroid follicles in suspension culture.

The effects of interferon-gamma (IFN gamma) on the morphology of thyroid follicles and the expression of major histocompatibility complex (MHC) class II antigens were examined. The thyroid follicles were suspended in RPMI-1640 containing 10% fetal calf serum with or without IFN gamma (200 U/ml). After culture for 5 days, follicles were incubated in the presence of TSH (10 mU/ml) for 1 h and fixed for electron microscopic and immunohistochemical examination. Regardless of the presence of IFN gamma, suspended follicles became inverted within 5 days. However, MHC class II antigens were expressed only in inverted follicles cultured with IFN gamma. In inverted follicles cultured without IFN gamma, TSH stimulation induced remarkable morphological changes, such as elongation of microvilli and an appearance of pseudopods. On the other hand, the follicles cultured with IFN gamma showed poor response to TSH. Thus, IFN gamma induced the expression of MHC class II antigens of cultured thyroid follicles and inhibited TSH-induced morphological changes in the cells.

Animals↗
PubMed1991

Human recombinant interleukin 1 inhibits TSH-stimulated morphological changes in thyroid follicles cultured as semi-organs.

To study the effects of human recombinant interleukin-1 on thyrocytes, we cultured thyroid follicles as semi-organs, each consisting of approximately 10-20 follicles, in the presence or absence of IL-1 alpha or beta. Semi-organ culture reproduces the in vivo environment well. After culture for 2 or 4 days, the follicles were incubated with TSH (10 U/l) for 4 h and fixed for light and electron microscopical examinations. Regardless of the presence or absence of IL-1, follicular structure, polarity, and luminal colloid did not change during culture. In thyroid epithelial cells cultured without IL-1, TSH markedly induced elongation of microvilli and formation of reabsorbed colloid droplets. On the other hand, both IL-1 alpha and beta inhibited these TSH-stimulated changes. The degree of inhibition correlated with the concentration of exposure to IL-1. We conclude that IL-1 inhibits TSH-stimulated morphological changes in thyroid follicles cultured as semi-organs, depending on the concentration of IL-1.

Animals↗
PubMed1991

Nicotinamide and 3-aminobenzamide reduce interferon-gamma-induced class II MHC (HLA-DR and -DP) molecule expression on cultured human endothelial cells and fibroblasts.

We investigated the effects of nicotinamide and 3-aminobenzamide, known as inhibitors of poly (ADP-ribose) synthetase, on the expression of interferon- gamma (IFN-gamma)-induced class I and II major histocompatibility complex (MHC) molecules on the surface of cultured human umbilical vein endothelial cells (HUVEC) and human dermal fibroblasts (HDF). Indirect immunofluorescent staining on HUVEC and HDF was performed using monoclonal antibodies against class I MHC (HLA-A,B,C) and class II MHC (HLA-DR, HLA-DP and HLA-DQ) molecules, and then the expression of these molecules was determined using a fluorescence flow cytometry. Human recombinant IFN-gamma (100 U/ml) increased the expression of HLA-A,B,C molecules, and induced the expression of HLA-DR molecules and, to a lesser extent, of HLA-DP on both HUVEC and HDF. HLA-DQ molecules were not induced by IFN-gamma on either cell type. Nicotinamide and 3-aminobenzamide in the concentration greater than or equal to 1 mM reduced the IFN- gamma -induced expression of HLA-DR and HLA-DP on both HUVEC and HDF, whereas neither agent in the concentration of up to 10 mM affected the IFN- gamma -induced increase in HLA-A,B,C molecule expression. These data suggest that nicotinamide and 3-aminobenzamide suppress antigen presenting function of class II MHC positive endothelial cells and fibroblasts at the site of tissue inflammation.

Animals↗
PubMed1991

Demonstration of islet cell antibodies in apparently non-insulin dependent diabetic patients; a marker for the later development of insulin dependency.

One hundred and ten diabetic patients who were apparently non-insulin dependent at 1984 were followed up for 5 years from 1984 to 1989. Islet cell antibodies (ICA) of the patients were tested in 1987. Eleven patients were positive for ICA and 99 were negative. There was no significant difference in age, sex, duration of diabetes, and HbA1c levels between ICA-positive and negative groups. Six of 11 (54.5%) patients in ICA-positive group developed insulin-requiring state in the period from 1984 to 1989, while only 5 of 99 (5.1%) patients in ICA negative group became insulin-requiring. Glucagon tolerance test (1 mg i.v.) was performed on 8 patients who developed insulin-requiring state; among them 4 patients were ICA-positive and other 4 patients were ICA negative. The serum C-peptide response to intravenous glucagon injection was markedly decreased in 3 of the 4 ICA-positive patients, and only mildly decreased in all the 4 ICA-negative patients. The markedly decreased C-peptide response indicates that these ICA-positive subjects had developed insulin-dependency. We conclude that the presence of ICA in apparently non-insulin dependent diabetics indicates a high risk for developing insulin-dependency.

Autoantibodies↗
PubMed1991

Lipopolysaccharide augments HLA-A,B,C molecule expression but inhibits interferon-gamma-induced HLA-DR molecule expression on cultured human endothelial cells.

The effect of bacterial lipopolysaccharide (LPS) on the expression of class I and II major histocompatibility complex (MHC) molecules on the surface of cultured human umbilical vein endothelial cells (HUVEC) was determined by indirect immunofluorescent staining followed by flow cytometric analysis. LPS at concentrations higher than 0.01 micrograms/ml augmented class I MHC (HLA-A,B,C) expression on HUVEC in a concentration-dependent manner. Optimal augmentation, approximately sixfold compared with control, was seen with 10 micrograms/ml of LPS. Time-course experiments indicated that the augmentation was maximal on Day 4. In contrast, LPS had no effect on the induction of class II MHC (HLA-DR) molecules and at concentrations higher than 0.01 micrograms/ml inhibited the interferon-gamma(IFN-gamma)-induced class II MHC expression. The inhibition was about 60% at the concentration of 100 micrograms/ml of LPS. Interleukin-1 (IL-1) had a similar effect as LPS on class I and II MHC expression. However, LPS appeared to affect MHC expression directly and not through production of IL-1 or cyclo-oxygenase pathway products, since anti-IL-1 antibodies or an inhibitor of cyclo-oxygenase pathway products, indomethacin, failed to reverse the effects of LPS. These data stress the role of LPS as a direct modulatory factor of class I and II MHC expression on endothelial cells during the development of immune and inflammatory response against Gram-negative bacteria.

Antibodies↗