Biomedical subjects

K Yamagata

Publications and source records attributed to K Yamagata.

At least 163 records · Page 9Linked to original sources

PubMed1994

[Analysis of the candidate antigen for Harada's disease].

The candidate antigen for Vogt-Koyanagi-Harada's (VKH) disease was isolated from cultured human melanoma cells (G-361). First, the soluble protein from the melanoma cells was separated into several fractions according to the molecular weight by gel filtration. In each fraction, the antigenicity was analysed by lymphocyte proliferation assay using peripheral blood lymphocytes (PBLs) from VKH disease patients. Then the positive fractions were further separated by liquid isoelectrofocusing followed by SDS polyacrylamide gel electrophoresis. In the liquid isoelectrofocusing fractions, the fraction at about pH 6.0 contained the antigenic protein. The protein from the 75 kDa band on the SDS-PAGE of this fraction was able to cause proliferation of the PBLs from the VKH disease patients. Thus, it appears that the 75 kDa protein of pH 6.0 isoelectrofocusing point was the specific autoimmune antigen for VKH disease.

Adult↗

PubMed1993

Labeling of lysine 492 with pyridoxal 5'-phosphate in the sarcoplasmic reticulum Ca(2+)-ATPase. Lysine 492 residue is located outside the fluorescein 5-isothiocyanate-binding region in or near the ATP binding site.

Sarcoplasmic reticulum vesicles were treated with 2 mM pyridoxal 5'-phosphate (PLP) at 25 degrees C and pH 7.0 for 6 min and reduced by NaBH4. Both the activity of the Ca(2+)-ATPase and the capacity for high affinity Mg-ATP binding were greatly reduced. Acetyl phosphate hydrolysis or phosphoenzyme formation from Pi was not inhibited. The enzyme was protected by high affinity Mg-ATP binding against the PLP-induced inhibition. A similar protective effect was obtained by Mg-AMP as well as by Mg-ADP. Acetyl phosphate or Pi gave no protection. The PLP-treated vesicles were solubilized in SDS, and the Ca(2+)-ATPase was purified by size exclusion high performance liquid chromatography (HPLC). Mapping the fluorescently labeled peptides in the tryptic digest by reversed phase HPLC revealed a single fluorescent peak, which was protected by Mg-ATP against labeling. Sequencing showed that Lys-492 is the residue labeled with PLP. These results demonstrate that Lys-492 is located in or near the ATP binding site but not in the phosphorylation site or the Pi binding site. When Lys-515 was entirely prelabeled with fluorescein 5-isothiocyanate (FITC), the subsequent labeling of Lys-492 with PLP was not prevented. This finding demonstrates that Lys-492 is located outside the FITC-binding region. It has been widely accepted that FITC occupies the adenosine-binding region within the ATP binding site. In contrast to FITC, Mg-AMP strongly inhibited the labeling of Lys-492 with PLP. These findings lead to the conclusion that Lys-492 is located outside the adenosine-binding region, most probably in or near the region occupied by the alpha-phosphoryl group of Mg-ATP bound to the ATP binding site.

Adenosine Diphosphate↗

PubMed1993

Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids.

Prostaglandins play important and diverse roles in the CNS. The first step in prostaglandin synthesis involves enzymatic oxidation of arachidonic acid, which is catalyzed by prostaglandin H(PGH) synthase, also referred to as cyclooxygenase. We have cloned an inducible form of this enzyme from rat brain that is nearly identical to a murine, mitogen-inducible cyclooxygenase identified from fibroblasts. Our studies indicate that this gene, here termed COX-2, is expressed throughout the forebrain in discrete populations of neurons and is enriched in the cortex and hippocampus. Neuronal expression is rapidly and transiently induced by seizures or NMDA-dependent synaptic activity. No expression is detected in glia or vascular endothelial cells. Basal expression of COX-2 appears to be regulated by natural synaptic activity in the developing and adult brain. Both basal and induced expression of COX-2 are inhibited by glucocorticoids, consistent with COX-2 regulation in peripheral tissues. Our studies indicate that COX-2 expression may be important in regulating prostaglandin signaling in brain. The marked inducibility in neurons by synaptic stimuli suggests a role in activity-dependent plasticity.

Aging↗

PubMed1993

Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients.

We examined pancreas biopsy specimens from 18 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients to elucidate the mechanism underlying beta cell destruction. Pancreas islets were seen in all patients and insulitis in eight patients. Infiltrating mononuclear cells consisted of CD4+T, CD8+T, B lymphocytes, and macrophages. Among them, CD8+T lymphocytes were predominant and macrophages followed. The expression of MHC class I antigens was increased in islet and endothelial cells in nine patients. MHC class II expression was increased in endothelial cells of the same patients. The expression of intercellular adhesion molecule-1 was increased in endothelial cells in two of the nine patients with MHC hyperexpression; in one of them, lymphocyte function-associated antigen-3 expression was also increased. Out of the eight patients with insulitis, seven showed MHC class I hyper-expression, whereas 2 of the 10 patients without insulitis showed the phenomenon (P < 0.05). The relation between insulitis and the hyperexpression of adhesion molecules was not evident. In conclusion, we revealed the close relation between CD8+T lymphocyte-predominant insulitis and MHC class I hyperexpression in islet cells. This suggests that infiltrating CD8+T lymphocytes recognize islet autoantigens in association with increased MHC class I molecules and act as major effector cells in autoimmune response against islet cells in IDDM pancreases. The role of adhesion molecules in the pathogenesis of IDDM still remains to be elucidated.

Adolescent↗

PubMed1993

Application of hydroxyapatite-coated implants as support for palatal lift prostheses in edentulous patients with cleft palate: a clinical report.

A palatal lift prosthesis (PLP) is a prosthetic speech aid used to compensate for palatopharyngeal incompetence. However, it requires dental abutments to facilitate its function. In two edentulous patients with cleft palate, hydroxyapatite-coated dental implants were used to increase PLP retention. In both cases, palatopharyngeal closure was obtained and PLP function was deemed effective, as determined by speech evaluation and nasal air flow measurements, for more than 3 years. This treatment is useful for enhancing the retention of a PLP in patients who have few or no remaining natural tooth abutments.

Adult↗

PubMed1993

Overexpression of HLA class I antigen reduces insulin secretion in pancreatic beta cells (RINM5F): evidence for a non-immune mechanism.

Our recent observation indicated that overexpression of HLA-class I antigen on pancreatic beta cells is one of the features of insulin-dependent diabetes mellitus (IDDM). To analyze the effect of class I antigen overexpression, we have introduced human HLA class I (HLA-Cw3) gene into rat pancreatic beta cell lines, RINm5F. Several stable transformants with various levels of surface expression of class I antigens have been cloned. The insulin secretion of these transfectants was analyzed to evaluate the functions of beta cells. Highly negative correlation between the level of insulin secretion and that of class I expression (correlation coefficiency: r = 0.89) has been observed. These data suggest that the overexpression of HLA class I antigen itself may impair pancreatic beta cells through a nonimmune mechanism.

Animals↗

PubMed1993

[A study to predict the clinical efficacy of house dust mite immunotherapy in bronchial asthmatics].

To predict the clinical efficacy of house dust mite immunotherapy (IT), clinical factors before IT were analyzed in relation to clinical efficacy in bronchial asthmatics treated by standard IT method. In 111 asthmatics treated by IT, 88 cases (80%) obtained favorable results over a one-year period, while only 39% of asthmatics without IT showed clinical improvement (p < 0.05, chi 2 test). Factors including severity, skin test threshold, age, age at which IT was started, duration of asthma, onset of asthma, FEV1.0% and serum IgE levels before IT were analyzed. Severity showed the most significant influence on clinical efficacy (r = 0.412, p < 0.01). A study to determine whether some specific criteria could be used to predict the clinical efficacy of IT was then carried out. Using multivariate analysis with the factors above mentioned, the clinical efficacy ranging from deteriorated to good response could be expressed as a formula with a multi-regression coefficient of 0.56, p < 0.05. Moreover, the application of linear discriminating analysis gave an 80% true positive discriminating rate in 75 asthmatics. In both methods, severity seemed to be the most important factor, skin test threshold next and FEV1.0% third. The other factors were not significant. Hopefully, the use of this formula in clinical practice will improve the efficacy of IT, thus providing further therapeutic benefits to bronchial asthmatics.

Adult↗

PubMed1993

An alternate nonisotopic technique of PCR-mediated allele-specific oligonucleotide analysis for the detection of a point mutation.

We report a simple protocol for the allele analysis of a point mutation using polymerase chain reaction. Conditions have been determined to use probes prepared for the conventional allele-specific oligonucleotide hybridization method directly. After amplification of the genomic region containing the mutation site, the nested polymerase chain reaction was performed using an allele-specific oligonucleotide probe as one side of the primer. Specificity of the amplification was achieved by decreasing the primer concentration in a two segment thermal cycling pattern. This protocol does not require additional special primers and an allelic mutation can be determined non-isotopically.

Alleles↗

PubMed1992

Morphological differentiation of endothelial cells co-cultured with astrocytes on type-I or type-IV collagen.

In this study bovine aortic endothelial cells were co-cultured with astrocytes from fetal Wistar Kyoto rats. Endothelial cells growing on type-I collagen, co-cultured with astrocytes, showed various stages of development. Although some cells appeared to be mature, horseradish peroxidase penetrated within 1 min of incubation through the intercellular junctions of these endothelial elements maintained on type-I collagen. In contrast, endothelial cells on type-IV collagen, co-cultured with astrocytes, were well developed; their intercellular junctions were well established, and plasmalemmal vesicles reduced in number. As a result, horseradish peroxidase was unable to penetrate through the endothelial cells grown on type-IV collagen and co-cultured with astrocytes because of the reduced extent of the junctional and vesicular transport. These findings reveal that (1) type-IV collagen is essential for the differentiation of endothelial cells, (2) endothelial cell-astrocyte interactions occur during co-culture, and (3) endothelial permeability depends on astrocyte-produced factors, in addition to type-IV collagen.

Animals↗

PubMed1992

Identification of glucocorticoid responsive elements (GREs) at far upstream of rat NPY gene.

The location of three glucocorticoid responsive elements (GREs) in rat neuropeptide Y (NPY) gene was determined by chloramphenicol acetyltransferase (CAT) assay and nucleotide sequencing. We have reported that mRNA content of rat prepro-NPY is increased by 1.7-fold in NG108-15 cells by 1 microM dexamethasone, suggesting the presence of GRE in the gene. To identify the element, the 5'-flanking DNA of 3.3 kilobases (kb) was isolated from rat NPY gene. When chimeric chloramphenicol CAT plasmids containing various deletions of the NPY upstream sequence were transfected into NG108-15 cells, the region between -2.9 and -2.1 kb relative to the cap site was found to potentiate the transcription of CAT gene in the presence of 1 microM dexamethasone. The nucleotide sequencing of this region revealed three GRE consensus sequences at -2.5, -2.2 and -2.1 kb. The results indicate that these elements present in the far upstream region of the NPY gene confer induction by glucocorticoids.

Animals↗

PubMed1992

[Effects of a specific thromboxane A2 synthetase inhibitor on lymphocyte and neutrophil functions in adult intractable asthmatics].

To clarify whether thromboxane A2 (TXA2) is involved in type III and IV allergy, or so called "cell-mediated allergy", we studied the effect of a specific TXA2 synthetase inhibitor, sodium ozagrel (OKY-046) on peripheral blood mononuclear cells and neutrophils in adult intractable asthmatics. The results revealed, firstly, that lymphocyte blastogenesis and interleukin-2 (IL-2) production from peripheral blood mononuclear cells stimulated by PHA and Candida antigen in intractable asthmatics was significantly suppressed dose-dependently by OKY-046. Secondly, there was a tendency that neutrophil chemotactic factor (NCF) and eosinophil chemotactic factor (ECF) from peripheral blood mononuclear cells stimulated by Candida antigen in intractable asthmatics were suppressed by OKY-046. Thirdly, leukotriene (LTC4) and superoxide (O2-) production from peripheral blood neutrophils in intractable asthmatics was significantly suppressed dose-dependently by OKY-046. That is, OKY-046 has a suppressive effect on type IV allergy caused by lymphocyte activation and on mediator release from neutrophils. These results suggest that TXA2 plays an important role in the development of bronchial asthma and OKY-046 might be a useful drug in the treatment of intractable asthmatics.

Adult↗

PubMed1992

[Two cases of paranasal sinusitis with choanal polyp in children].

Patients with choanal polyp often suffer from maxillary sinusitis of the same side. Hence, Caldwell-Luc operation in addition to polypectomy has been recommended for the treatment of choanal polyp. Choanal polyp occurs more frequently in children with nasal polyp(s) than in adults with nasal polyp(s). For this reason, it is preferable to perform surgery so as to preserve the maxillary sinus as much as possible. The authors surgically treated two children with choanal polyp. A 12-year-old girl had a choanal polyp arising from the posterior portion of the middle turbinate and received an osteoplastic maxillary operation and functional endoscopic sinus surgery (FESS). The other, a 13-year-old girl, with an antro-choanal polyp underwent FESS only. One year after surgery, both patients showed no recurrence of polyp and had recovered an aerated maxillary sinus cavity covered with normal mucous membrane. Based on the experiences of these two cases, FESS appears to be very helpful in treating children with choanal polyp and paranasal sinusitis.

Adolescent↗

PubMed1992

[Studies on IgG subclass antibodies in adult asthma. 2. Changes in serum antigen specific IgG subclass antibodies for aging and intractability in asthmatics].

To clarify the factors which induce intractable asthma, the level of serum IgG subclass antibodies to mite (Dermatophagoides farinae) and Candida antigens (Candida albicans) for aging and severity was investigated in 230 bronchial asthmatics (Male: 117, Female: 113) aged 6-81 years old (mean age = 40). Total IgE level and IgE antibodies to mite and Candida antigens were measured by radioimmunosorbent test (RIST) and radioallergosorbent test (RAST), respectively. The serum level of IgG and IgG1 antibodies to the antigens were measured by enzyme-linked immunosorbent assay (ELISA). The results were as follows: 1) The incidence of severe asthma in aged and late onset asthmatics, especially late onset intractable asthma (LOIA), was higher than that in young and early onset asthmatics. 2) The serum level of total IgE and IgE antibodies to mite in aged and late onset asthmatics was lower than that in young and early onset asthmatics. 3) The incidence of severe and intractable asthmatics in the group of low IgE levels (less than 300 IU/ml) was higher than that in the group of high IgE levels (over 500 IU/ml). The incidence of positive IgE (RAST) score to mite in severe and intractable asthmatics was lower than that in mild and moderate asthmatics. 4) Considering aging, the serum levels of IgG and IgG1 antibodies to mite and Candida in severe and intractable asthmatics was higher than those in mild asthmatics. These data indicate that the aged and late onset asthmatics may produce dominantly the IgG (IgG1) antibody to the antigens, and have severe asthma attacks caused by IgG (IgG1) rather than IgE antibody.

Adolescent↗

PubMed1992

Significance of deposits and abnormalities of the glomerular basement membrane in tissue injury accompanying IgA nephropathy.

The glomerular injuries in 129 cases of IgA nephropathy (IgA-N) were examined ultrastructurally with special reference to the glomerular basement membrane (GBM) deposits and capillary loop abnormalities, and the correlation between these findings and the clinicopathological data was analyzed. The following results were obtained. 1) The degree of daily excretion of urine protein (UP) and creatinine clearance (Ccr) revealed a significant correlation with the degree of mesangial hypercellularities and the frequency of segmental lesions. 2) All sites of GBM deposits, and discontinuity and/or splitting among the GBM abnormalities showed a significant relation to the severity of proliferation and segmental lesions. 3) The GBM deposits, discontinuity and splitting showed a significant relation to the degree of UP and Ccr. We speculate therefore that capillary loop deposits and/or capillary loop discontinuity and splitting could represent histological prognostic factors for an unfavorable outcome in IgA nephropathy.

Adolescent↗

PubMed1991

Expression of liver type pyruvate kinase in insulinoma cells: involvement of LF-B1 (HNF1).

The messages for LF-B1, which interacts with the cis-acting element of PKL-I to play an essential role in expression of L-type pyruvate kinase (PK) in the liver, and L-type PK were found to be present in RIN-m5F insulinoma cells as well as the liver, kidney and small intestine, although the levels of the two mRNAs in these tissues were not correlated. Gel retardation assay suggested that similar nuclear proteins bound to two other cis-acting elements, PKL-II and PKL-III, were expressed in both liver and insulinoma cells, and that additional PKL-III-binding proteins were present only in RIN-m5F cells. Thus, we suggest that the mechanism of L-type PK expression in pancreatic B cells is similar to that in the liver.

Animals↗

PubMed1991

HLA-DQA11 contributes to resistance and A13 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

Histologic findings of apatite-titanium complex dental implants in the jaws of dogs.

This study concerns the histologic examination of apatite-titanium complex dental implants (two-piece, cylindrical type) in dogs. There was no plaque control. One to 3 months after implantation, the surface of the apatite root was directly bound to newly formed, woven bone. Seven-and-a-half months to 1 year after implantation, the apatite root was directly bound to the newly formed lamellar bone, which provided strong bone bonding (apatite-bone bonding). There appear to be two types of mechanisms for the resorption of apatite ceramics: first, cellular-type resorption by both multinuclear and mononuclear macrophages; and second, a noncellular, fluid mechanism (dissolution). The gingival sulcus around implants and downward growth of the epithelial cells could be observed in almost all of the implants. There was no cellular inflammation in the tissue around the implants, in the nasal cavity, or in the maxillary sinus. From this study we concluded that clinical application of this dental implant system would be practical.

Animals↗

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↗