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Biomedical subjects

M Ono

Publications and source records attributed to M Ono.

At least 127 records · Page 7Linked to original sources

Glycosylation affects translocation of integrin, Src, and caveolin into or out of GEM.

Endogenous GM3 synthesis and full N-glycosylation in membrane receptors occurred in "4-epimerase-less" ldlD (Krieger's CHO mutant) cells cultured in Gal-containing medium, whereby components of detergent-insoluble, low-density, buoyant membrane fraction, termed "glycolipid-enriched microdomain (GEM)," varied significantly by translocation into or out of GEM. Integrins alpha3 and alpha5 were translocated into GEM in the presence of 0.5 or 0.25% Triton X-100, particularly in the absence of Gal, whereby integrins are underglycosylated and GlcCer is the major glycolipid component in GEM. Src family kinase was translocated into and enriched in GEM fractions when prepared in 0.5 or 0.25% Triton X-100 from cells grown in Gal-containing medium, whereby GM3 synthesis is induced. In contrast, caveolin is highly enriched in GEM when GM3 synthesis does not occur, and is translocated into high-density membrane fraction when GM3 synthesis occurs. The results suggest that levels of key molecules controlling cell adhesion and signaling are defined by translocation into or out of GEM, which depends on glycosylation state.

Animals↗

Cytological and immunological changes in bronchoalveolar lavage fluid and histological observation of lung lesions in pigs immunized with Mycoplasma hyopneumoniae inactivated vaccine prepared from broth culture supernate.

We have compared the cytology of bronchoalveolar lavage fluid (BALF) and the pathology of lung lesions in pigs immunized with/without Mycoplasma hyopneumoniae inactivated vaccine prepared from broth culture supernate on experimental infection. Numbers of total cells, macrophages, neutrophils and lymphocytes have decreased in BALF of vaccinated pigs following infection. The mean percentage of lung lesions, inflammatory cell infiltration into the airways and T cells accumulation around the bronchi were reduced in vaccinated pigs. The levels of tumor necrosis factor (TNF)-alpha also decreased in vaccinated pigs. These results suggest that the vaccination may contribute to decrease TNF-alpha production, and therefore, inflammatory cell responses in the lung due to M. hyopneumoniae infection were suppressed, resulting in fewer lung lesions.

Animals↗

Isolation of porcine epidemic diarrhea virus in porcine cell cultures and experimental infection of pigs of different ages.

This paper describes the isolation of porcine epidemic diarrhea (PED) virus in Vero and porcine cell cultures, and the influence of age on disease in experimental infection. PED virus was isolated from the small intestine of piglets inoculated with PED samples and cultured in Vero, porcine bladder and kidney cells propagated in collagen-coated tissue culture plates in maintenance medium (MM) containing trypsin. In porcine bladder and kidney cell cultures inoculated with isolated PED virus, cytopathic effects (CPE) including cell fusion were detected. Specific brilliant fluorescence was observed in the cytoplasm of these cells. Two- and 7-day old, and 2-, 4-, 8- and 12-week old specific pathogen-free (SPF) pigs were orally inoculated with PED virus isolated from an outbreak. All 2- and 7-day old pigs inoculated developed severe watery diarrhea from post-inoculation day (PID) 1 and died between PID 3 and 4. Although three of five 2-week old pigs developed diarrhea on PID 1-4, they eventually recovered. In the 4-week old group, three of five pigs had mild diarrhea for 1-2 days. None of the 8- and 12-week old pigs showed any clinical signs. Antibodies against PED virus were detected in all surviving pigs by virus neutralization (VN) test and immunofluorescence assay (IFA). Therefore, there is an age-dependent resistance to pathogenic PED virus infection in pigs.

Age Factors↗

Fcgamma receptor IIB-deficient mice develop Goodpasture's syndrome upon immunization with type IV collagen: a novel murine model for autoimmune glomerular basement membrane disease.

The combination of hemorrhagic pneumonitis and rapidly progressive glomerulonephritis is a characteristic feature of Goodpasture's syndrome (GPS), an autoimmune disease resulting from the interaction of pathogenic anti-collagen type IV (C-IV) antibodies with alveolar and glomerular basement membranes. Lack of a suitable animal model for this fatal disease has hampered both a basic understanding of its etiology and the development of therapeutic strategies. We now report a novel model for GPS using mice deficient in a central regulatory receptor for immunoglobulin (Ig)G antibody expression and function, the type IIB Fc receptor for IgG (FcgammaRIIB). Mutant mice immunized with bovine C-IV reproducibly develop massive pulmonary hemorrhage with neutrophil and macrophage infiltration and crescentic glomerulonephritis. The distinctive linear, ribbon-like deposition of IgG immune complex seen in GPS was observed along the glomerular and tubulointerstitial membranes of diseased animals. These results highlight the role of FcgammaRIIB in maintaining tolerance and suggest that it may play a role in the pathogenesis of human GPS.

Animals↗

Absolute configuration of aflastatin A, a specific inhibitor of aflatoxin production by Aspergillus parasiticus.

Aflastatin A (1) is a specific inhibitor of aflatoxin production by Aspergillus parasiticus. It has the novel structure of a tetramic acid derivative with a long alkyl side chain. The absolute configurations of 29 chiral centers contained in 1 were chemically elucidated in this study. First, four small fragment molecules were prepared from 1 or its methyl ether (2), and their absolute structures were assigned as N-methyl-D-alanine, (2S,4R)-2, 4-dimethyl-1,6-hexanediol dibenzoate, (R)-3-hydroxydodecanoic acid, and (R)-1,2,4-butanetriol tribenzoate. Next, an acyclic fragment molecule 3 with 13 chiral centers was obtained from 1 by NaIO(4) oxidation, and its relative stereochemistry was elucidated by J-based configuration analysis. By analyzing coupling constants of (3)J(H,H) and (2,3)J(C,H) and ROE data, the relative configuration of 3 was verified. Finally, by further J-based configuration analysis using a fragment molecule 7 prepared from 2 with 28 chiral carbons, all relative configurations in the alkyl side chain of 1 were clarified. By connecting these relative configurations with the absolute configurations of first four fragment molecules, the absolute stereochemistry of 1 was fully determined.

Aflatoxins↗

Macrophage infiltration correlates with tumor stage and angiogenesis in human malignant melanoma: possible involvement of TNFalpha and IL-1alpha.

We examined whether macrophage infiltration is associated with angiogenesis in cutaneous melanoma. The numbers of macrophages and microvessels increased significantly with increasing depth of tumor and with tumor angiogenesis. Macrophage infiltration thus appeared to provide a useful diagnostic marker for the progression of cutaneous melanoma. We further examined whether human melanoma cells produce angiogenic factors in response to macrophage-derived cytokines, tumor necrosis factor alpha (TNFalpha) and interleukin-1 alpha (IL-1alpha). Treatment of melanoma cells with TNFalpha and IL-1alpha in vitro enhanced the production of interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF), and of basic fibroblast growth factor (bFGF) to a lesser degree, in human melanoma cells. Lipopolysaccharide (LPS)-activated human monocytes enhanced production of IL-8, VEGF, TNF alpha, as well as IL-1alpha, but not bFGF. Co-culture of human monocytes and human melanoma cells was also found to significantly enhance production of IL-8 and VEGF in the absence and presence of LPS, compared with either monocytes or melanoma cells alone. The production of IL-8 and VEGF from co-cultured melanoma cells and LPS-activated monocytes was blocked when anti-TNF-alpha antibody or anti-IL-1alpha antibody was co-administrated. This is direct evidence that production of the potent angiogenic factors IL-8 and VEGF from melanoma cells is up-regulated through TNFalpha and/or IL-1alpha secreted by activated monocytes/macrophages, influencing both tumor growth and angiogenesis in melanomas.

Adult↗

Upregulation of brain somatostatin and neuropeptide Y following lidocaine-induced kindling in the rat.

Male Sprague-Dawley rats received a daily injection of 60 mg/kg of lidocaine (> 30 days). Twenty percent of rats developed convulsions (kindled rats) and remaining rats did not show convulsions (non-kindled rats). The level of immunoreactive somatostatin (IR-SRIF) in kindled rats was significantly increased in amygdala than that in non-kindled rats and control rats. Immunoreactive neuropeptide Y (IR-NPY) contents in kindled rats were significantly increased in amygdala, hippocampus, cortex and striatum compared to non-kindled and control rats. The expression of SRIF mRNA in kindled rats produced a significant increase in amygdala, while NPY mRNA in kindled rats showed an elevated expression in both amygdala and hippocampus. These results coincide with the previous findings with the elevated expression of SRIF and NPY mRNA in electrically and pharmacologically kindled models, suggesting the important role of these peptides in the kindling phenomenon.

Amygdala↗

Metastatic hepatocellular carcinoma obstructing the right ventricular outflow tract.

A 49-year-old female with a past history of liver resection due to hepatocellular carcinoma was referred to our Department for treatment of a metastatic cardiac tumor obstructing the right ventricular outflow tract. She underwent operation twice with cardiopulmonary bypass, and symptoms were relieved. Metastasis from hepatocellular carcinoma to the heart is very rare, but should be taken into consideration during follow-up after treatment for a primary liver tumor.

Carcinoma, Hepatocellular↗

Effects of phencyclidine on behavior and extracellular levels of dopamine and its metabolites in neonatal ventral hippocampal damaged rats.

RATIONALE: The use of neonatal hippocampal lesioned rats is well established in animal models of schizophrenia. Moreover, the dysfunction of N-methyl-D-aspartate (NMDA) neurotransmission may play a crucial role in the pathophysiology of schizophrenia. OBJECTIVE: To examine the role of NMDA neurotransmission in the neonatal ventral hippocampal damaged rat. METHODS: In initial experiments, we compared the effects of mild environmental stress (HAB) and the injection of saline and methamphetamine (MAP, 1.5 mg/kg, IP) in lesioned and sham-operated rats. We also examined the effects of a single injection of phencyclidine (PCP, 10 mg/kg, IP) on locomotor activity and extracellular levels of dopamine (DA) and its metabolites in the nucleus accumbens (NAc) of lesioned and sham-operated rats using an in vivo brain microdialysis method. RESULTS: Compared with sham-operated controls, the lesioned rats showed increased locomotor activity at postnatal day 56 (PD56) but not at PD35 after HAB and MAP administration. Similarly, the lesioned rats showed increased locomotor activity at PD56 but not at PD35 after PCP administration. Unexpectedly, the increase in DA levels was significantly greater in the sham-operated rats than in the lesioned rats. CONCLUSIONS: The results suggest that neonatal hippocampal lesioned rats are accompanied by the dysfunction of NMDA neurotransmission. They also suggest that hyperresponsiveness to PCP following neonatal hippocampal lesions does not depend on the extracellular DA concentration in the NAc.

Animals↗

Unusual core histones specifically expressed in male gametic cells of Lilium longiflorum.

We have cloned three novel histone genes using antibodies that recognize only nuclei of the male gametic (generative and sperm) cells of Lilium longiflorum. The deduced amino acid sequence of each clone shows only between 40% and 50% identity with the H2A, H2B and H3 somatic core histones of other plant species. Transcripts of these genes were first detected in bicellular pollen soon after microspore mitosis, and their mRNAs, as revealed by in situ hybridization, were observed only in the cytoplasm of the generative cells. As expression of these three genes was specific to generative cells within the bicellular pollen, we designated the clones gH2A, gH2B and gH3. Immunocytochemistry further revealed that the proteins encoded by these genes accumulated in the elongating and condensing generative nucleus during development of bicellular pollen, and were most abundant in the two sperm nuclei within an elongated pollen tube. We therefore propose that these male gamete-specific core histones contribute to chromatin condensation of male gametes or to chromatin remodeling, and result in the repression of gene expression in male gametes.

Amino Acid Sequence↗

Aortobronchial fistula late after transverse arch replacement.

We report an unusual case of aortobronchial fistula late after transverse arch replacement caused by the remnant of a temporary bypass near the ascending aorta. In reconstructive surgery of the ascending aorta, antegrade perfusion is preferably performed through a side branch after completion of the distal anastomosis by some surgeons. This report suggests possible risk of a serious late complication unless the side branch is placed and tailored properly.

Aged↗

Intermittent administration of brain-derived neurotrophic factor ameliorates glucose metabolism in obese diabetic mice.

We have previously shown that brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, interacts with the endocrine system in obese diabetic mice, and systemic peripheral administration of BDNF regulates glucose metabolism in this model. Results from the present study show that the hypoglycemic effect induced by 2 weeks' daily administration of BDNF (20 mg/kg/d) to db/db mice lasts for several weeks after treatment cessation, irrespective of food reduction. On the other hand, the antidiabetic agent, metformin had no lasting effect. This duration of the BDNF hypoglycemic action prompted us to examine the efficacy of BDNF intermittent administration on glucose metabolism. BDNF administered once or twice per week (70 mg/kg/wk) to db/db mice for 3 weeks significantly reduced blood glucose concentrations and hemoglobin A(1c), (HbA(1c)) as compared with ad libitum-fed phosphate-buffered saline (PBS)-treated and pair-fed PBS-treated groups. This suggests that BDNF not only temporarily reduced blood glucose concentrations but also ameliorated systemic glucose balance in this obese diabetic mouse model during the experimental period. Our results indicate that BDNF could be a novel hypoglycemic agent with an exceptional ability to normalize glucose metabolism even with treatment as infrequently as once per week.

Animals↗

Diterpenoids from the fruits of Vitex trifolia.

An abietane-type diterpene, named vitetrifolin A, and two labdane-type diterpenes, named vitetrifolins B and C, were isolated from the acetone extract of the fruits of Vitex trifolia L. (Viticis Fructus; Verbenaceae) along with three known diterpenes, rotundifuran, dihydrosolidagenone and abietatriene 3beta-ol. The structures of these compounds were elucidated on the basis of spectroscopic analysis, X-ray crystallographic analysis and chemical evidence.

Crystallography, X-Ray↗

Eudesmane derivatives from Tessaria integrifolia.

Five eudesmane-type sesquiterpenoids were isolated from the methanol extract of the aerial part of Tessaria integrifolia Ruiz. et Pavon (Compositae). Their structures were elucidated on the basis of spectroscopic analysis is well as chemical evidence.

Asteraceae↗

Bone metastasis after a resection of stage I and II primary lung cancer.

In the present study, we reviewed the patients who developed bone metastases after a surgical resection of primary lung cancer and evaluated their clinicopathological features. From 1992 to 1995, 177 patients with stage I and II primary lung cancer underwent a surgical resection at the Kitakyushu Municipal Medical Center. Bone metastases were detected in 14 patients (7.9%) by follow-up examinations including bone scintigraphy (scan). Bone metastasis was one of the most frequent extra-thoracic recurrent forms. Patients with adenocarcinoma tended to develop bone metastases more frequently than those with squamous cell carcinoma. In the preoperative bone scans, an abnormal uptake was observed in 76 patients (42.9%), and 10 (13.1%) of them were found to develop bone metastases in the follow-up studies. A microscopic examination of the primary tumor demonstrated close correlation between intratumoral and peritumoral lymphatic vessel invasion and postoperative development of bone metastases. A bone scan is a very useful and indispensable procedure for diagnosing bone metastases. However, this scan may also show false positive finding in a number of benign conditions. Therefore, a surgical resection should be considered as the first-line treatment for patients with positive findings in the bone scan when the diagnosis of bone metastasis can not be confirmed based on both their symptoms and other clinical examinations.

Adenocarcinoma↗

Age-related association of MHC class I chain-related gene A (MICA) with type 1 (insulin-dependent) diabetes mellitus.

To assess the contribution of the HLA class I region to susceptibility to and heterogeneity of type 1 diabetes, we investigated the association of polymorphism of MHC class I chain-related gene A (MICA) with age-at-onset as well as susceptibility to type 1 diabetes. One hundred one Japanese patients and 110 healthy control subjects were studied. The frequency of A4 allele was significantly higher and that of A6 allele was significantly lower in patients than in control subjects. The frequency of A5.1 allele was highest in early-onset patients (23.0%), intermediate in intermediate-onset patients (9.2%) and lowest in late-onset patients (7.7%) (trend chi-squared test, p = 0.0098). A5. 1 allele was strongly associated with HLA-B7 and Cw7, suggesting that MICA*A5.1-B7-Cw7 haplotype contains a gene responsible for age-at-onset. A4 allele was associated with a susceptible haplotype, DR4-DQB1*0401, and A6 allele was associated with a protective haplotype, DR2-DQB1*0601, suggesting that the association of MICA with type 1 diabetes susceptibility may be due to linkage disequilibrium with class II haplotypes. These data suggest that MICA gene is associated with age-at-onset and that a gene (or genes) responsible for age-at-onset of type 1 diabetes is located in the HLA class I region, probably near the region of MICA-B-C.

Adolescent↗

Liquid chromatographic determination of FP-21399 in plasma of patients with HIV infection.

A high-performance liquid chromatographic (HPLC) analysis method for the novel anti-HIV drug FP-21399 in human plasma was developed. The method employed the combination of organic solvent extraction and solid phase extraction. Analysis of FP 21399 and two major metabolites was achieved within 18 min using a reverse phase Puresil Cl 8 analytical column (4.6 x 150 mm, 5 microm, Waters) with a mobile phase of water-acetonitrile containing 20 mM triethylamine acetate (apparent pH 7.0). Linear gradient of mobile phase was applied as water-acetonitrile from 78:22 (v/v) to 55:45 over 8 min, and held at this ratio for the next 4 min. An ultraviolet-visible detector was operated at 265 mn from 0 to 8 min and at 600 mn from 8 min and after. The retention time of FP-21399 was 8.8 min and a linear response was observed over the concentration range 0.01 100 microg ml(-1) (r = 0.994). Lower limit of quantitation was found to be 0.01 microg ml(-1). Intra- and inter-assay precision varied in the range of 0.2 to 8% and 1-12%, respectively. The bias ranged from -17-3% for all analyses. A series of clinical plasma specimens were successfully analyzed using this method. The strategies for the method optimization on HIPLC separation and extraction procedure are discussed as well.

Anti-HIV Agents↗