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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 379 records · Page 21Linked to original sources
PubMed1997

Identification of human and mouse GP-1, a putative member of a novel G-protein family.

To identify genes induced in monocytes by interferon-gamma, we carried out PCR-based cDNA subtraction and subsequent differential display on mRNA isolated from a human monocytic leukemia cell line, THP-1. We detected a novel gene encoding a protein bearing GTP-binding motifs, the characteristics of GTP-binding proteins (G-proteins). We also identified the mouse homologue of this gene and designated the gene GP-1. The amino acid sequence of GP-1 deduced from the nucleotide sequence is highly conserved in human and mouse (97% identical over the entire protein), suggesting a fundamental physiological role for this molecule. As amino acid sequences of GTP-binding motifs of human and mouse GP-1 are practically identical to those of recently identified putative G-proteins of nematode, AGP-1 and CGP-1, these proteins are likely to be members of the same, novel G-protein family. GP-1 mRNA was readily detected in mouse brain, thymus, lung, and kidney, while GP-1 mRNA is rarely expressed in liver.

Amino Acid Sequence↗
PubMed1997

Involvement of Fas antigen in ovarian follicular atresia and luteolysis.

The Fas antigen (Fas) is a cell-surface receptor protein that mediates apoptosis-inducing signals and plays an important role in the immune system. Significant amounts of Fas mRNA can be detected not only in lymphoid organs but also in the liver, heart, and ovary. In the ovary, apoptosis is thought to cause follicular atresia and luteolysis. We have investigated the involvement of Fas in these events. Here we report that Fas protein is expressed on granulosa and luteal cells but not on oocytes in the ovary. An injection of anti-Fas monoclonal antibody with apoptosis-inducing activity into adult mice enhanced follicular atresia and luteolysis. After the injection, the corpora lutea disappeared and the number of follicles containing pyknotic granulosa cells increased. There were also fewer ovulated ova and lower levels of luteal cell-produced progesterone. Furthermore, as the result of a non-functional Fas/Fas ligand system, mature ovaries from the mouse mutant/pr (lymphoproliferation) were histologically abnormal in terms of follicular development, in that the number of secondary follicles significantly increased. These results suggested that Fas plays an important role in follicular atresia and luteolysis in the ovarian physiology of adult mice.

Animals↗
PubMed1997

Messenger RNA fingerprinting analysis using arbitrarily primed PCR (RAP) of genes expressed during rat C6 glioma cell differentiation.

To identify differentially expressed genes involved in rat C6 glioma cell differentiation induced by cyclic AMP, we adopted mRNA fingerprinting using arbitrarily primed polymerase chain reaction (PCR) (RAP). Four complementary DNA (cDNA) fragments differentially expressed during differentiation were isolated, and they appeared to contain coding regions of corresponding mRNAs. RAP can be used to efficiently identify cDNA fragments by comparing nucleotide and deduced amino acid sequences with those in databases, and is thus a useful method to search for and identify important genes involved in complex cellular processes such as glioma cell differentiation.

Animals↗
PubMed1997

Germinoma in cerebral hemisphere associated with Down syndrome.

A Down syndrome patient with germinoma developing in the cerebral hemisphere is reported. A review of the literature yielded only 14 cases of Down syndrome with brain tumors, including our case. This finding of brain tumors in patients with Down syndrome may reflect chance occurrence. However, it is of interest in this regard that in 6 of the 14 (43%) reported cases the lesions were intracranial germ cell tumors.

Adolescent↗
PubMed1997

Superoxide dismutase-like immunoreactivity in spheroids in Hallervorden-Spatz disease.

Iron accumulation in the basal ganglia and spheroid formation are pathological hallmarks of Hallervorden-Spatz disease (HS). Since an overaccumulation of iron (iron thesaurosis) that exceeds the binding capacity of ferritin could cause oxidative damage, we studied the possible role of oxidative stress in the pathogenesis of HS. The basal ganglia and spinal cord from patients with HS were investigated at autopsy, using histochemistry for iron and immunohistochemistry for Cu/Zn superoxide dismutase (SOD1), Mn superoxide dismutase (SOD2) and ferritin. SOD1-like immunoreactivity (IR), SOD2-IR and ferritin-IR occurred frequently in spheroids observed in the basal ganglia, and associated iron accumulation indicated the possible existence of increased oxidative stress in HS patients. Spheroids in the spinal cord showed intense SOD1-IR and SOD2-IR in HS, in sharp contrast with the occasional weak SOD1-IR and SOD2-IR observed in spheroids from patients with amyotrophic lateral sclerosis (ALS). Neither increased ferritin-IR nor iron accumulation were observed in spinal spheroids from HS and ALS patients. These data may suggest that, at least in the spinal cord, SOD1-IR and SOD2-IR in spheroids in HS patients do not result from oxidative stress directly related to iron accumulation.

Adult↗
PubMed1997

Suppression of mouse contact hypersensitivity after treatment with antibodies to leukocyte function-associated antigen-1 and intracellular adhesion molecules-1.

We investigated the effects of the antibodies against the adhesion molecules leucocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) on mouse allergic contact hypersensitivity. Mice were injected intraperitoneally with both antibodies before sensitization by an epicutaneous application of dinitrofluorobenzene (DNFB). Simultaneous administration of the antibodies induced suppression of ear swelling in the effector phase of contact hypersensitivity. To show the effect of antibodies in vitro, lymph node cells (LNC) of mice treated with antibodies or with phosphate-buffered saline (PBS) were cultured in the presence of dinitrobenzene sulphonic sodium salts (DNBS), and the production of interleukin-2, interleukin-4 and interleukin-10 in the culture supernatants was measured using an enzyme-linked immunosorbent assay (ELISA). It was found that the production of interleukin-2 in the cells of mice treated with the antibodies was significantly lower than in the cells of PBS-treated mice. On the other hand, no difference was noted in the production of interleukin-4 or interleukin-10. Our results indicate that in vivo simultaneous administration of antibodies to cell adhesion molecules before hapten sensitization induces the suppression of contact hypersensitivity in mice and that the suppression may be due to the inhibition of the production of interleukin-2.

Animals↗
PubMed1997

Acute effects of pioglitazone on glucose metabolism in perfused rat liver.

Pioglitazone, a thiazolidinedone derivative, decreases insulin resistance and improves hyperglycemia in insulin-resistant obese and/or diabetic animals. However, the mechanisms by which hyperglycemia is improved are not well defined. We investigated the effects of pioglitazone on hepatic glucose metabolism using a perfused rat liver model. Perfusion with the buffer containing 1-10 microM pioglitazone for 20 min dose-dependently increased the hepatic fructose 2,6-bisphosphate content, a potent activator of 6-phosphofructo 1-kinase. The fructose 2,6-bisphosphate level after 20 min perfusion with 10 microM pioglitazone was 64.9 +/- 14.5 pmol/mg.protein, significantly higher than the control (48.3 +/- 10.9 pmol/mg.protein). When the liver from a starved for 48 h rat was perfused with the buffer containing 2 mM lactate but no glucose, glucose was generated from lactate via the gluconeogenic pathway and flowed into the effluent perfusate at a constant rate of 31 +/- 0.6 mumol/g.liver/h. The addition of 10 microM pioglitazone decreased the glucose output rate to 19.3 +/- 3.8 mumol/g.liver/h. Dose-dependent inhibition of glucose output by pioglitazone was observed in the 1-10 microM dose range. These results indicate that pioglitazone may not only stimulate glycolysis but also inhibit gluconeogenesis in the liver. These acute and insulin-independent effects on hepatic glucose metabolism may partly account for the diverse anti-diabetic effects of pioglitazone.

Administration, Oral↗
PubMed1997

Surgical strategy for doubly committed subarterial ventricular septal defect with aortic cusp prolapse.

BACKGROUND: Many surgeons recommend early repair of doubly committed subarterial ventricular septal defect regardless of the clinical symptoms. We reviewed our patients of this anomaly with aortic cusp prolapse to justify this strategy. METHODS: We reviewed the preoperative and postoperative records of 27 patients with doubly committed subarterial ventricular septal defect and aortic cusp prolapse. The patients' ages ranged from 2 months to 11 years (median, 4.6 years). RESULTS: During the preoperative observation period, aortic regurgitation (AR) developed in 65% of the patients. In the 8 patients without AR before the operation, AR did not develop after the operation, whereas AR persisted in 12 (63%) of the 19 patients with preoperative AR. To identify the risk factors for persistent AR after the operation we analyzed the data for the patients with preoperative AR in the persistent AR group (n = 12) and eliminated AR group (n = 7) and found a longer period from the onset of AR to the operation in the persistent AR group (32.1 +/- 10.1 versus 5.6 +/- 1.9 months; p = 0.014). During the follow-up period 10 of the 17 patients with mild AR before the operation showed persistent AR in the postoperative period, but it did not progress. CONCLUSIONS: We conclude that early surgical repair with a minimum observation period is essential for prevention of residual AR. Even if a tiny AR is detected preoperatively, the patient should be surgically treated immediately.

Age Factors↗
PubMed1997

Immunocytochemical study of cathepsin L and rat salivary cystatin-3 in rat osteoclasts treated with E-64 in vivo.

The localization of cathepsin L and rat salivary cystatin-3 (RSC-3) in rat osteoclasts (rat femoral and alveolar bones) treated with or without E-64 (control) was examined immunocytochemically. In osteoclasts pretreated with E-64, immunoreactivity for cathepsin L was very weak extracellularly compared to that in the control osteoclasts. However, it was strong intracellularly. The localization of RSC-3 was unclear in the control osteoclasts, while in E-64 treated osteoclasts, both the clear zone and ruffled border areas showed a very strong immunoreaction. At the electron-microscopic level, in normal osteoclasts, numerous immunoreaction products for cathepsin L were found extracellularly in the bone matrix under the ruffled border, while few intracellular products were observed. In contrast, in the E-64-treated osteoclasts, only a few immunoreaction products were found extracellularly, while intracellularly cathepsin L was found in numerous endosome-lysosomal vacuoles. In the immunoreaction for RSC-3, the cytoplasm of the ruffled border was positive, and the tips of the RSC-3-positive ruffled border appeared to enter deeply into the bone matrix. Intracellularly, the granular reaction products of RSC-3 were found in the vacuoles (probably autophagolysosomes). Thus, in E-64-treated osteoclasts, inhibition of the extracellular release of cathepsin L was demonstrated. In addition, intralysosomal accumulation of RSC-3 and deep penetration of the RSC-3-positive ruffled border into the bone matrix were found. These findings suggest that RSC-3 is associated with the inhibition of cathepsin L in both the lysosomes (in the osteoclasts) and bone matrix.

Animals↗
PubMed1997

Organ perfusion with Hemopump device assistance with and without intraaortic balloon pumping.

OBJECTIVE: Our objective was to analyze the potential advantage of combining an intraaortic balloon pump with a transthoracic Hemopump device (Medtronic, Inc., Minneapolis, Minn.) (Nimbus Medical, Inc., Rancho Cordova, Calif.). METHODS: Twelve sheep underwent implantation of a transthoracic Hemopump device and an intraaortic balloon pump. In the first series (n = 6), we analyzed the influence of the counterpulsation on the performance of the Hemopump device. In the second group (n = 6), hemodynamic changes, myocardial wall thickening, organ perfusion, and myocardial perfusion (determined with colored microspheres) were analyzed under the following conditions: (1) control situation, (2) during application of coronary stenosis, (3) during support with the Hemopump device, and (4) during support with the Hemopump device combined with intraaortic balloon pump support. RESULTS: In the first series, we found that addition of counterpulsation reduced output with the Hemopump device by 11.1% +/- 6%. In the second series, it was shown that coronary stenosis significantly reduced contractility (rate of pressure change and wall thickening) but did not cause hemodynamic collapse. Myocardial blood flow was significantly reduced in the poststenotic subendocardial regions (mean subendocardial blood flow dropped from 78 +/- 33 to 24 +/- 17 ml/min/100 gm; p = 0.0486). Support with the Hemopump device alone improved the ratio of subendocardial to subepicardial blood flow, but endocardial underperfusion remained (analysis of variance, p < 0.001). The Hemopump device with an intraaortic balloon pump completely restored perfusion in poststenotic regions. Peripheral organ perfusion did not change during ischemia or mechanical support. CONCLUSIONS: The association of balloon counterpulsation with the Hemopump device reduces the Hemopump output by 11% and increases myocardial blood flow to ischemic regions. Perfusion to peripheral organs remains unaltered. The transthoracic Hemopump device combined with an intraaortic balloon pump is an ideal support system for the ischemic, failing heart.

Analysis of Variance↗
PubMed1997

Epidermal growth factor binding sites in the mouse exocrine and endocrine pancreas shown by in vivo quantitative microautoradiography and confocal laser scanning microscopy.

Microautoradiography at 3, 6 and 15 min after intravenous injection of 125I-EGF was used to investigate the distribution of epidermal growth factor (EGF) binding sites in the pancreas of normal male mice. The autoradiographs were observed by confocal laser microscopy, which allows the quantification of silver grains. The results demonstrated that both endocrine and exocrine pancreatic cells exhibited substantial specific binding of 125I-EGF. The highest level of EGF binding was found in the duct cells of the exocrine pancreas followed by the acinar cells. The cells of the islets of Langerhans also showed substantial specific binding of 125I-EGF though the binding level was lower than that of the exocrine pancreas. In the control experiments, mice were injected with 125I-EGF and various amounts of unlabeled EGF.

Animals↗
PubMed1997

Genomic structure of the bovine mb-1 gene encoding the Ig-alpha subunit of the B cell antigen receptor complex.

The B cell antigen receptor, (BCR) comprises surface immunoglobulin and disulfide-bonded heterodimer of Ig-alpha and Ig-beta chains, which are the products of the mb-1 and B29 genes, respectively. In this study, we describe the isolation and analysis of a 6.2-kb genomic DNA clone containing bovine mb-1 gene encoding Ig-alpha. Sequence data revealed that the bovine mb-1 gene is composed of five exons and four introns, and that its overall structure is very similar to those of murine and human genes. The 5' upstream region of the bovine mb-1 gene contained potential protein binding motifs of transcription factors including EBF, Sp1, NF-kappa B, MUF/Ets-1 and AP 2. As with the murine and human mb-1 genes, the 5' region of the bovine mb-1 gene lacked a TATA box. The present study will be useful for understanding the regulated expression of the bovine mb-1 gene at different stages of development and activation as well as in bovine leukemia virus infection.

Amino Acid Sequence↗
PubMed1997

Molecular characteristics of malignant lymphomas in cats naturally infected with feline immunodeficiency virus.

Neoplastic disease, especially malignant lymphomas, are often observed in cats infected with feline immunodeficiency virus (FIV). In order to clarify the characteristics of lymphoma cells and to investigate the pathogenesis in FIV-infected cats, we examined the lymphoma tissues developed in five cats naturally infected with FIV by Southern blot analyses using feline immunoglobulin (Ig), T-cell receptors (TCR) and FIV probes. All of the five cases were serologically positive for anti-FIV antibody and negative for feline leukemia virus antigen. Of these five lymphoma samples, two displayed rearrangement of the Ig heavy chain gene and deletion of the Ig light (kappa) chain gene, indicating that the tumor cells were committed to B-cell development. One tumor sample was identified as a T-cell lymphoma because of the presence of a rearranged TCR beta-chain gene. The other two cases were considered to be non-T non-B cell lymphoma because they did not show any rearrangement of the Ig and TCR genes. Therefore, no consistent tumor type was found in lymphoma cases infected with FIV. Clonal integration of FIV provirus was not detected in any of the five lymphoma samples obtained from FIV-infected cats using Southern blot analysis, although FIV proviral genome was detected in the genomic DNA of all the lymphoma samples by using a polymerase chain reaction (PCR). These results indicated that FIV might not play a direct role in tumorigenesis of lymphoma in cats.

Animals↗
PubMed1997

The N-terminal six residues of peptide core sequences suffice for binding to HLA-DR4 (DRB1*0405) and DR9 (DRB1*0901) molecules.

When examining anchor residues of a peptide 0405BP2 (1SPGTGAYYVLLN12) that was eluted from purified HLA-DR4 molecules (DRA/DRB1*0405), we found that heptamer peptides K7YYVLLN12 and K7YAALAN12 could bind to DR4 with the same affinity as 0405BP2, where artificially added Lys increases the solubility of peptides, and 7Y, 10L and 12N function as major anchor residues. In contrast, none of K8YVLLN12, K8AALAN12, K7YYVLL11 and K7YAALA11 had any detectable binding. Similar results were obtained with peptide K1WAASAAAAA9 that binds to DR9 (DRA/DRB1*0901) where 1W and 4S function as major anchor residues; K1WAASAA6, but not K1WAASA5 or K2AASAAAAA9 did bind to DR9 molecules. These data indicate that, when the most N-terminal anchor is designated as P1 (position 1), P1-6 but not P7-9 is essential, for binding at least to HLA-DR4 and DR9 molecules.

Amino Acid Sequence↗
PubMed1997

Topographic distribution and collateral projections of the two major populations of nigrothalamic neurons. A retrograde labeling study in the rat.

The principal target nuclei of nigrothalamic projections in the rat are the mediodorsal (MD) and ventromedial (VM) nuclei. The present study examined the patterns of distribution and collateral projections of the two major groups of nigrothalamic neurons, i.e., nigro-MD and nigro-VM neurons. Retrograde fluorescent labeling with Fluoro-Gold was used to examine whether the distribution areas of nigro-MD and nigro-VM neurons might be overlapped with or segregated from each other in the substantia nigra pars reticulata. A clear tendency was observed that nigro-MD neurons were distributed more ventrally than nigro-VM neurons. It was further examined by retrograde fluorescent double labeling with Fluoro-Gold and Fluoro-Ruby whether or not these nigrothalamic neurons might provide axon collaterals to the superior colliculus or the pontine reticular formation. The nigro-MD neurons were found to send axon collaterals to the superior colliculus more frequently than the nigro-VM neurons. Additionally, a small number of nigrothalamic neurons were found to send axon collaterals to the pontine reticular formation. The functional significance of the two major populations of nigrothalamic neurons was discussed on the basis of their collateral projections to the superior colliculus or the pontine reticular formation.

Animals↗
PubMed1997

Nonscarring inflammatory epidermolysis bullosa acquisita with esophageal involvement and linear IgG deposits.

A 24-year-old woman with autoimmune thrombocytopenia and hypothyroidism had an inflammatory bullous eruption in the mouth, face, and trunk that left no milia or scars after healing. Histologic examination revealed a subepidermal bulla and a neutrophil infiltration. Direct immunofluorescence examination showed deposition of IgG and C3 in the basement membrane zone (BMZ). Indirect immunofluorescence examination with 1M sodium chloride-split skin showed IgG binding to the dermal side. Immunoblot analysis demonstrated IgG autoantibodies reacting with 290 kD dermal protein. We diagnosed this as epidermolysis bullosa acquisita (EBA) with a nonscarring inflammatory feature. Treatment with oral dapsone, 75 mg, and prednisolone, 20 mg, cleared the eruption. Reduction of the prednisolone dosage was associated with multiple erosions in the esophagus. Direct immunofluorescence examination revealed linear deposition of IgG in the esophageal BMZ. To our knowledge, this is the first report of EBA with esophageal involvement and deposition of IgG in the BMZ of the esophagus.

Adult↗
PubMed1997

Differential binding of peptides substituted at putative C-terminal anchor residue to HLA-DQ8 and DQ9 differing only at beta 57.

HLA-DQ8 (DQA1*0302-DQB1*0302: DQ beta 57 Ala) and (DQA1*0302-DQB1*0303: DQ beta 57 Asp) differ only at beta 57, at which polymorphism reportedly confers distinct susceptibility to insulin-dependent diabetes mellitus (IDDM). To identify the differential peptide binding affected by beta 57, we determined DQ9-binding peptides by affinity-based selection of a phage random peptide library using the biotinylated DQ9 complex. Nonconservative single-residue substitution of high-affinity DQ8- and DQ9-binding peptide (1KLPDYVLWSSSTVVGLGAAGA21) at the underlined residues significantly decreased the peptide binding to DQ8 and DQ9. Affinities of the wild-type 21-mer K4DYVLWSSSTV13 and K4AYAAWAAATA13 to DQ8 and DQ9 were practically the same. The K4DYVLWSSSTV13-based analogue peptides with substitutions at 12T showed that residues R, K, H, E, D, Q, N, T, S, V, L, I, F, M, W, and Y permitted binding to DQ8, whereas only R, T, V, L, I, F, M, W, and Y did so to DQ9. Thus, significant differences exist between DQ9 and DQ8, in that the majority of polar residues, regardless of their static charges at the residue 12, permitted binding to IDDM-susceptible DQ8, which is not the case for DQ9. The affinities of K4DYVLWSSSXV13 AND K4AYAAWAAAAX13 (where X is T, A, K, D, or I) were almost equal to DQ8 and DQ9, suggesting the DQ8- and DQ9-binding peptide motifs could accept both the 8-mer and 9-mer frames depending on intervening sequences between N- and C-terminal anchor residues. The biochemical basis of peptide-HLA interactions determined by DQ beta 57 is discussed.

Amino Acid Sequence↗