Search PubMed⌕ Search

Biomedical subjects

T Koga

Publications and source records attributed to T Koga.

At least 145 records · Page 8Linked to original sources
PubMed1999

Cutaneous metastasis from hepatocellular carcinoma resembling pyogenic granuloma.

A case of skin metastasis from hepatocellular carcinoma (HCC) is reported that resembled pyogenic granuloma. An easily bleeding, cutaneous nodule on the chin of a 62-year-old Japanese male was resected under the diagnosis of pyogenic granuloma. Histology, however, indicated HCC. Cutaneous metastases from HCC are very rare, but the possibility must be considered for unusual nodules resembling pyogenic granuloma.

Carcinoma, Hepatocellular↗
PubMed1999

Giant cell interstitial pneumonia in two hard metal workers: the role of bronchoalveolar lavage in diagnosis.

Two cases of hard metal lung disease and pathological findings of giant cell interstitial pneumonia are reported. The cases worked in different factories manufacturing hard metal parts from tungsten carbide and cobalt. Pathological specimens were obtained by percutaneous thoracoscopy and transbronchial lung biopsy. X-ray microanalysis detected only tungsten carbide in the lung specimen of one case. Bronchoalveolar lavage showed diagnostic bizarre macrophages in the lavage fluid.

Adult↗
PubMed1999

A novel apolipoprotein E mutation, E2 (Arg25Cys), in lipoprotein glomerulopathy.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is characterized by intraglomerular lipoprotein thrombosis and high plasma concentrations of apolipoprotein (apo) E. An apo E variant, apo E2 (Arg145Pro) Sendai, was recently identified in three patients with LPG. We detected a novel point mutation in the apo E gene in a patient with LPG, and we characterized the mutant apo E. METHODS: The propositus was a 32-year-old male patient on maintenance hemodialysis because of LPG. The mutation was detected by sequencing of genomic DNA from the patient and was confirmed by restriction fragment length polymorphism (RFLP) with Aor51HI. Recombinant apo E2 (Arg25Cys) Kyoto and normal apo E3 were expressed from COS-1 cells. Low-density lipoprotein (LDL) receptor-binding activities of the variants were determined in an in vitro competition assay. RESULTS: The propositus had the apo E phenotype E2/E4, as determined by isoelectric focusing, and the genotype epsilon3/epsilon4, as determined by RFLP with HhaI. Sequence analysis of amplified DNA showed a C to T transition, changing the codon for residue 25 from arginine to cysteine. The proband was a heterozygous carrier for apo E2 (Arg25Cys) Kyoto. A family study showed that the mother was a heterozygous carrier of apo E2 Kyoto and had dysbetalipoproteinemia, but no LPG. The pathophysiological effect of this mutation was investigated in vitro by binding studies of recombinant apo E2 Kyoto to LDL receptors on human fibroblasts. The ability of recombinant apo E2 Kyoto to displace LDL was reduced to 10% compared with recombinant apo E3. CONCLUSIONS: Apo E2 (Arg25Cys) Kyoto is a novel mutation of apo E that is etiologically related to LPG. However, our case indicates that the development of LPG may involve other genetic or environmental factors. Furthermore, our data suggest that arginine-25 of apo E plays an important functional role by influencing the receptor-binding ability of apo E.

Adult↗
PubMed1999

gammadelta T cells regulate mucosally induced tolerance in a dose-dependent fashion.

We used gammadelta TCR-deficient (TCRdelta(-/-)) mice to examine the role of gammadelta T cells for induction of mucosal responses and systemic tolerance to high versus low doses of oral antigen. When either TCRdelta(-/-) or TCRdelta(+/+) mice were immunized orally with a high dose of ovalbumin (OVA) prior to parenteral challenge, systemic IgG and IgE antibody responses were markedly reduced in both types of mice, while mucosal IgA responses were reduced only in the TCRdelta(-/-) mice. Reduced T cell proliferative responses and delayed-type hypersensitivity were seen in TCRdelta(-/-) and TCRdelta(+/+) mice given the high dose of OVA. Antigen-induced T(h)1 and T(h)2 cytokine production by splenic CD4(+) T cells was severely inhibited in orally tolerized TCRdelta(-/-) and TCRdelta(+/+) mice. In contrast, while oral tolerance associated with increased levels of IL-10 synthesis was induced by a low dose of OVA in TCRdelta(+/+) mice, the TCRdelta(-/-) mice were not tolerized and failed to produce IL-10. Our findings indicate that gammadelta T cells play a significant immunoregulatory role in IL-10-mediated, low-dose oral tolerance induction, but are not essential participants in the induction of systemic tolerance to orally introduced antigens given in larger doses.

Animals↗
PubMed1999

Bovine milk antibodies against cell surface protein antigen PAc-glucosyltransferase fusion protein suppress cell adhesion and alter glucan synthesis of Streptococcus mutans.

Cell surface protein antigen (PAc) and glucosyltransferases (GTF) produced by Streptococcus mutans are considered major colonization factors of the organism, and the inhibition of these factors is thought to prevent dental caries. In this study, 8-mo-old pregnant Holstein cows were immunized with fusion protein PAcA-GB, a fusion of the saliva-binding alanine-rich region (PAcA) of PAc with the glucan binding (GB) domain of GTF-I, an enzyme catalyzing the synthesis of water-insoluble glucan from sucrose. High titers of immunoglobulin antibodies specific for the fusion protein were found in normal milk after reimmunization, and they persisted for approximately 3 mo. The immunoglobulin G (IgG) antibodies against PAcA-GB were purified from immunized milk. The antibodies significantly inhibited the adhesion of S. mutans cells to saliva-coated hydroxyapatite beads. IgG antibodies purified from immunized milk also inhibited total glucan synthesis by cell-associated GTF preparation and GTF-I from S. mutans. The immunized milk may be useful as a means of passive immunization for the prevention of dental caries in humans.

Animals↗
PubMed1999

EPR studies on the photo-induced intermediates of ferric NO complexes of rat neuronal nitric oxide synthase trapped at low temperature.

Rat neuronal nitric oxide synthase (nNOS) was expressed in Escherichia coli and purified. Although the nitric oxide (NO) complex of the ferric heme was EPR-silent, photo-illumination at 5 K to the NO complex of the ferric nNOS in the substrate-free form produced a new high spin EPR signal similar to that of the ferric heme of N(omega)-nitro-L-arginine-bound nNOS, suggesting that the photo-dissociated NO might move away from the heme. Low photo-dissociability of NO in this complex indicated less restricted movement of the dissociated NO in the distal region of the heme, which might result in the rapid rebinding of the NO to the ferric heme at 5 K. In the presence of substrate L-arginine, derivatives, or product L-citrulline, the photo-products from the ferric NO complexes exhibited large novel EPR signals with a spin-coupled interaction between the ferric heme (S = 5/2) and the photolyzed NO (S = 1/2), suggesting a stereochemically restricted interaction between the photo-dissociated NO and the guanidino- or the ureido-group of the substrate analogues at the distal heme region of nNOS. The photo-product from the NO complex produced from citrulline-bound nNOS might be the same intermediate species as that formed in the last step of the catalytic cycle.

Animals↗
PubMed1999

Roles of cytokines and cell cycle regulating substances in proliferation of cholesteatoma epithelium.

OBJECTIVES: It can be surmised that the cell cycle must be involved in cell proliferation of the epithelium of middle ear cholesteatoma. Thus a comparative study was conducted of the levels of expression of cyclin-dependent kinase 2 (cdk2) and cyclin-dependent kinase 4 (cdk4)-substances known to be involved in the cell cycle-in cholesteatoma epithelium and the normal epithelium of the bony region of the external ear canal. In addition, it has been reported that the expression of cytokines in the epithelium is accelerated in response to subepithelial inflammation. This suggests that an interaction between the epithelium and subepithelium, which is subject to paracrine regulation, is deeply involved in epithelial proliferation. Accordingly, attention was focused on interleukin-1alpha (IL-1alpha) and keratinocyte growth factor (KGF), cytokines which are found in the subepithelium, and experiments were conducted to elucidate their effects on the expression of the substances known to be involved in the cell cycle. METHODS: The expressions of cdk2 and cdk4 in the cholesteatoma epithelium and external ear canal epithelium were investigated by an immunohistochemical technique. In addition, cultured human keratinocytes were grown in medium containing IL-1alpha or KGF at concentrations of 0, 20, and 100 ng/mL, and the differences in the expression of cdk2 and cdk4 were investigated and compared by Western blot analysis. RESULTS: In the cholesteatoma epithelium specimens, cdk2 and cdk4 were observed to be expressed in the basal and parabasal layers and in the upper layer (prickle layer and granular layer). Their expression tended to be increased compared with their expression in the normal external ear canal epithelium, and this tendency was marked in subepithelial sites showing severe inflammation. In addition, exposure of cultured human keratinocytes to IL-la or KGF resulted in accelerated expression of both cdk2 and cdk4, and this was especially striking in the case of addition of KGF. CONCLUSION: It can be surmised that, in cholesteatoma, accelerated expression of IL-1alpha and KGF by inflammatory cells at subepithelial sites of inflammation leads to upregulation of cdk2 and cdk4 in epithelial cells and to cell proliferation. It was concluded that this is at least one sequence of events involved in the mechanism causing epithelial proliferation in cholesteatoma.

Adult↗
PubMed1999

Terminal differentiation of epithelial cells in middle ear cholesteatoma: investigation of patterns of expression of protein kinase C-delta and protein kinase C-eta.

OBJECTIVES: The objective of this study was to elucidate the differentiation mechanism of keratinocytes in cholesteatoma. STUDY DESIGN: To achieve the objective, we analyzed the expressions of various cellular proteins: the delta and eta isoforms of protein kinase C (PKCdelta and PKCeta), which are thought to play key roles in signal transduction in differentiation; cytokeratin 1 (CK1) and cytokeratin 10 (CK10) (cytoskeletal constitutive proteins); and involucrin (a marker of differentiation). METHODS: The materials used in this study were tissue specimens obtained from cholesteatoma epidermis, normal external ear canal skin, normal inguinal skin, and psoriatic skin. Immunohistochemical staining techniques were applied to compare the expressions of the above proteins (i.e., PKCdelta, PKCeta, CK1, CK10 and involucrin) in those various tissues. RESULTS: No clear differences in the patterns of expression of PKCdelta and PKCeta were found between the cholesteatoma epidermis and the normal external ear canal skin. These proteins were expressed mainly in the stratum spinosum and stratum granulosum, and their patterns of expression were almost the same as those of the CK1, CK10, and involucrin proteins. CONCLUSION: The findings of this study indicate that the terminal differentiation of keratinocytes in the cholesteatoma epidermis is the same as in normal skin tissues. It was concluded that the growth of epidermis which has undergone hyperproliferation of keratinocytes because of increased levels of various cytokines is being regulated by means of normal terminal differentiation.

Adult↗
PubMed1999

Coexistence of ordered and disordered phases in a nearly symmetric diblock copolymer near an order-disorder transition point.

We investigated the phase behavior near the order-disorder transition (ODT) temperature in a nearly symmetric diblock copolymer, using ultra-small-angle x-ray scattering method. In a narrow temperature range very close to the ODT temperature, we observed the scattering profiles that can be interpreted as a linear combination of the scattering from the disordered state and that from the ordered lamellar state. These profiles were stable during the observation time (50 h), revealing that the two-phase coexistence occurs at thermal equilibrium within this temperature range.

Journal Article↗
PubMed1999

Long-range density fluctuations in a symmetric diblock copolymer.

We present an experimental piece of evidence of the excess small-angle-scattering in a nearly symmetric diblock copolymer. This phenomenon is observed only in the two-phase coexistence region of the ordered and disordered phases near the order-disorder transition temperature, using the ultra-small-angle x-ray scattering method. This excess scattering is found to be caused by the difference of the density between the ordered and disordered phases in the coexistence region.

Journal Article↗
PubMed1999

Recombination between gtfB and gtfC is required for survival of a dTDP-rhamnose synthesis-deficient mutant of Streptococcus mutans in the presence of sucrose.

The rml genes are involved in dTDP-rhamnose synthesis in Streptococcus mutans. A gene fusion between gtfB and gtfC, which both encode extracellular water-insoluble glucan-synthesizing enzymes, accompanied by inactivation of the rml genes was observed for cells grown in the presence of sucrose. The survival rates of rml mutants isolated in the absence of sucrose were drastically reduced in the presence of sucrose. The rates were consistent with the frequency of spontaneous gene fusions between gtfB and gtfC, suggesting that the spontaneous recombinant organisms were selected in the presence of sucrose. The rml mutants with a gtfB-gtfC fusion gene had markedly reduced water-insoluble glucan synthetic activity and lost the ability to colonize glass surfaces in the presence of sucrose. These results suggest that the rml mutants of S. mutans, which are defective in dTDP-rhamnose synthesis, can survive only in the absence of water-insoluble glucan synthesis.

Gene Expression Regulation, Bacterial↗
PubMed1999

A novel gene required for rhamnose-glucose polysaccharide synthesis in Streptococcus mutans.

Gene rgpG is required for biosynthesis of rhamnose-glucose polysaccharide (RGP) in Streptococcus mutans. Its deduced amino acid sequence had similarity to WecA, which initiates syntheses of enterobacterial common antigen and some O antigens in Escherichia coli. Gene rgpG complemented a wecA mutation of E. coli, suggesting that rgpG may function similarly in RGP synthesis.

Cloning, Molecular↗
PubMed1999

Acanthosis nigricans with severe obesity, insulin resistance and hypothyroidism: improvement by diet control.

We report on a 27-year-old man with acanthosis nigricans (AN) associated with severe obesity, insulin resistance and hypothyroidism. A very low-calorie diet treatment decreased his weight and then ameliorated the insulin-resistant state. These effects were followed by remarkable improvement of the AN prior to the correction of the hypothyroidism. This confirms that AN may be mainly attributed to insulin resistance rather than hypothyroidism per se.

Acanthosis Nigricans↗
PubMed1999

Invasive thymoma with long-term survival by extensive reoperation.

The recurrence of invasive thymoma is often observed; however, no accepted treatment of recurrent invasive thymoma has yet been established. We herein report a 41-year-old woman with invasive thymoma and pleural dissemination who demonstrated long-term survival after undergoing 4 operations. Based on our findings, reoperation is thus suggested in patients with intrathoracic recurrence and long-term survival can be expected.

Adult↗
PubMed1999

Compound heterozygosity for an apolipoprotein A1 gene promoter mutation and a structural nonsense mutation with apolipoprotein A1 deficiency.

Apolipoprotein (apo) A1 plays a central role in the metabolism of HDL. We describe a novel genetic variant of the apoA1 gene identified in a patient with low concentrations of plasma HDL cholesterol. The proband, a 12-year-old Japanese boy, exhibited markedly low levels of both plasma apoA1 and HDL cholesterol. Genomic DNA sequencing of apoA1 genes of the patient showed a compound heterozygosity for an A to C substitution at 27 bp upstream of the transcription start site of 1 apoA1 allele, and a C to T substitution in another allele at residue 84 resulting in aberrant termination. The point mutation at nucleotide position -27 changed ATAAATA of the putative TATA box signal sequence to ATACATA. In addition to this mutation, the patient was heterozygous for a G to A substitution at position -75. Immunoblotting of an isoelectric focusing electrophoresis gel of the proband's plasma showed a trace amount of normal apoA1. No measurable plasma apoA1 and HDL cholesterol in a patient with homozygosity for nonsense mutation at residue 84 has been reported previously. To determine the effects of substitution either at position -27 or -75, plasmids containing the 5'-flanking region of the human apoA1 promoter fused to the CAT reporter gene were constructed and transfected in HepG2 cells. A construct with the A to C substitution at position -27 showed 41. 8+/-4.2%, and G to A substitution at position -75 showed 72.8+/-15. 2% (means+/-SD, n=3) of CAT activities, compared with the wild-type promoter sequence. A construct with the double substitutions at positions -27 and -75 showed only 22.8+/-1.3% (mean+/-SD, n=3) activity relative to the wild type. Our patient is the first case with a TATA box mutation etiologically related to lipoprotein disorders.

Apolipoprotein A-I↗
PubMed1999

A novel mutant, ApoA-I nichinan (Glu235-->0), is associated with low HDL cholesterol levels and decreased cholesterol efflux from cells.

A novel variant of apolipoprotein (apo) A-I associated with low high density lipoprotein (HDL) cholesterolemia has been identified in a Japanese family during screening for apoA-I variants by isoelectric focusing (IEF) gel analysis. ApoA-I (Glu235-->0) Nichinan was caused by a 3-bp deletion of nucleotides 1998 through 2000 in exon 4 of the apoA-I gene. Four subjects in the family were heterozygous carriers for this mutation; the mean plasma concentrations of apoA-I and HDL cholesterol of affected family members were 30% and 32% lower, respectively, than those of unaffected family members. There were no differences in the levels of very low density lipoprotein and low density lipoprotein cholesterol, triglycerides, and other apolipoproteins between the carriers and the noncarrier family members. In the proband, plasma lecithin:cholesterol acyltransferase activity was normal. Functional consequences of the mutation were examined by expressing the mutated and wild-type proapoA-I cDNAs in Escherichia coli. Cholesterol efflux to recombinant proapoA-I Nichinan from mouse peritoneal macrophages loaded with [3H]cholesterol-labeled acetylated low density lipoprotein was decreased by 54% when compared that of normal recombinant proapoA-I. In vivo turnover studies in normal rabbits demonstrated that the recombinant proapoA-I Nichinan was rapidly cleared (22% faster) compared with normal recombinant proapoA-I. We conclude that apoA-I (Glu235-->0) Nichinan induced a critical structural change in the carboxyl-terminal domain of apoA-I for cellular cholesterol efflux and increased the catabolism of apoA-I, resulting in low HDL cholesterol levels.

Adolescent↗