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T Koda

Publications and source records attributed to T Koda.

At least 37 records · Page 2Linked to original sources

Functional heterogeneity among bone marrow-derived dendritic cells conditioned by T(h)1- and T(h)2-biasing cytokines for the generation of allogeneic cytotoxic T lymphocytes.

Three distinct bone marrow (BM)-derived dendritic cells (BMDC) were expanded from BALB/c BM cells by culture with (i) granulocyte macrophage colony stimulating factor (GM-CSF) plus IL-3, (ii) GM-CSF, IL-3 plus T(h)1-biasing cytokines (IL-12 and IFN-gamma) or (iii) GM-CSF, IL-3 plus T(h)2-biasing cytokines (IL-4). All of these cells expressed the DC-specific marker CD11c, and were designated as BMDC0, BMDC1 and BMDC2 cells respectively. BMDC1 cells exhibited superior T cell-stimulating activity in allogeneic mixed lymphocyte culture (MLC), while BMDC2 showed inferior stimulating activity. Specifically, BMDC1, as compared with BMDC2, induced a higher frequency of IFN-gamma-producing CD8(+) T cells in MLC. Moreover, BMDC1, but not BMDC2, were strong inducers of H-2(d)-specific cytotoxic T lymphocytes (CTL) in MLC. BMDC0 always showed intermediate stimulatory activity; however, when BMDC0 were cultured with IFN-gamma, they differentiated into BMDC1-like stimulator cells concomitant with the up-regulation of both MHC antigens and co-stimulatory molecules. In contrast, BMDC2 were refractory to differentiation into superior stimulator cells by treatment with IFN-gamma, although this treatment enhanced MHC expression. These findings indicate that T(h)1- and T(h)2-biasing cytokines, in addition to their effect on T(h) cell differentiation, may play a critical role in the functional skewing of DC. These findings have important implications for the development of DC-based immunotherapies.

Animals↗

The interface between innate and acquired immunity: glycolipid antigen presentation by CD1d-expressing dendritic cells to NKT cells induces the differentiation of antigen-specific cytotoxic T lymphocytes.

In vivo administration of NKT cell ligand, alpha-galactosylceramide (alpha-GalCer), caused the activation of NKT cells to induce a strong NK activity and cytokine production by CD1d-restricted mechanisms. Surprisingly, we also found that alpha-GalCer induced the activation of immunoregulatory cells involved in acquired immunity. Specifically, in vivo administration of alpha-GalCer resulted in the induction of the early activation marker CD69 on CD4(+) T cells, CD8(+) T cells and B cells in addition to macrophages and NKT cells. However, no significant induction of CD69 was observed on cells from CD1d- or V(alpha)14 NKT-deficient mice, indicating an essential role for the interaction between NKT cells and CD1d-expressing dendritic cells (DC) in the activation of acquired immunity in response to alpha-GalCer. Indeed, in vivo injection of alpha-GalCer resulted not only in the activation of NKT cells but also in the generation of CD69(+)CD8(+) T cells possessing both cytotoxic T lymphocyte (CTL) activity and IFN-gamma-producing ability. Tumor-specific CTL generation was also accelerated by alpha-GalCer. The critical role of CD40-CD40 ligand (CD40L)-mediated NKT-DC interaction during the development of CD69(+)CD8(+) CTL by alpha-GalCer was demonstrated by blocking experiments using anti-CD40L mAb. These findings provide direct evidence for a critical role of CD1d-restricted NKT cells and DC in bridging innate and acquired immunity.

Adjuvants, Immunologic↗

[Effects of fudosteine, a new cysteine derivative, on airway secretion in rabbits and rats].

We examined the effects of fudosteine [(-)-(R)-2-amino-3-(3-hydroxypropylthio) propionic acid], a new cysteine derivative, on airway secretion in rabbits and rats. Indirect measurement of airway secretion in rabbits, which was expressed by the amount of dye excreted into the respiratory tract, was carried out according to the Sakuno's method, with some modifications. Fudosteine (500 mg/kg, p.o.) significantly increased the amount of dye excreted into the respiratory tract. As a direct method of measurement of airway secretion, the modified Perry and Boyd's method was used to collect respiratory tract fluid (RTF) in rabbits. Fudosteine (500 mg/kg, p.o.) significantly augmented the output volume of RTF, but there was no difference from the control in protein and phosphatidylcholine (PC) contents into RTF. On the other hand, fudosteine increased chloride ion concentration in broncho-alveolar lavage of rats. Fudosteine did not stimulate PC secretion in a primary culture of rat type II pneumocytes, and it did not have a mucolytic effect against gastric mucin in vitro. From the results described above, it was concluded that fudosteine may be a new cysteine derivative which offers a serous secretion.

Animals↗

Features of IgA nephropathy in preschool children.

AIM: The aim of this study is to clarify the age-related characteristics of pediatric IgA nephropathy. PATIENTS AND METHODS: Five cases in preschool children less than 6 years old were analyzed and compared to 38 cases in older children from 6 to 15 years old. RESULTS: The group of younger children had higher incidences of gross hematuria, hypertension, proteinuria, and hypoproteinemia. Renal biopsy specimens in this group showed more intracapillary lesions including mesangial cell proliferation and endocapillary proliferation ofglomeruli, but less segmental lesions, global sclerosis, and interstitial changes. CONCLUSION: IgA nephritis in preschool children demonstrated more symptoms of acute onset and less chronic renal injury.

Adolescent↗

Cloning of the mouse gene for D-dopachrome tautomerase.

D-Dopachrome tautomerase converts 2-carboxy-2,3-dihydroindole-5, 6-quinone (D-dopachrome) into 5,6-dihydroxyindole. The amino acid sequence of this protein is 27% identical with that of macrophage migration inhibitory factor, which is known as a cytokine, pituitary hormone, and glucocorticoid-induced immunomodulator. In this study, we isolated and sequenced a 3490 bp-long genomic DNA of mouse D-dopachrome tautomerase that consists of three exons and two introns. By two procedures, 5' rapid amplification of cDNA ends and cap site labeling, we determined the transcription initiation site, which is located 46 bp upstream of the translation initiation site. The possible polyadenylation sequence (AATAAA) is located 180 bp downstream of the termination codon. Computer-assisted analysis of the nucleotide sequence revealed a number of regulatory motifs, including multiple sites for Sp1, C/EBP, NF-Y, and USF. Although the precise pathophysiological functions of D-dopachrome tautomerase remain to be elucidated, the present results will contribute not only to elucidation of the mechanism of gene expression, but also to understanding of the molecular function of this protein.

Amino Acid Sequence↗

Nuclear targeting activity associated with the amino terminal region of the Borna disease virus nucleoprotein.

The Borna disease virus (BDV) replicates in the nucleus. The viral p40 protein (N), which is found abundantly in the nucleus in BDV-infected cells, may play an important role in virus replication. To analyze the amino acid residues involved in the nuclear targeting of BDV N, a series of eukaryotic expression plasmids encoding deletion mutants of N was constructed and transfected into COS-7 cells. In indirect immunofluorescence assays with a rabbit anti-BDV N antiserum, wild-type N was located in the nucleus of transfected cells in the absence of other viral constituents. In contrast, mutants lacking the 13 NH2-terminal amino acid residues 1MPPKRRLVDDADA13 in common gave a cytoplasmic localization pattern. Similarly, a mutant with substitution of 4KRR6 by 4NSG6 was retained in the cytoplasm. Furthermore, a nonapeptide, 3PKRRLVDDA11, derived from the NH2-terminal region of N conferred nuclear targeting activity to beta-galactosidase, which normally resides in the cytoplasm. Thus, we have identified the nuclear targeting signal of the BDV N and narrowed it to the NH2-terminal region where 4KRR6 basic amino acid residues are located.

Animals↗

Stimulation of bone formation in vivo by insulin-like growth factor-II in rats.

Insulin-like growth factor-II (IGF-II) plays an important role in skeletal remodeling, however, little is known about its effect on bone formation in vivo. In our study of the stimulation of bone formation in vivo by IGF II we injected recombinant human IGF-II into the parietal bones of neonatal rats once a day for 12 days. The bone mineral density measured by dual energy X-ray absorptiometry and the thickness of IGF-II-injected parietal bones increased in a dose-dependent manner. The layers of osteoblasts were observed along the IGF-II-injected side.

Animals↗

Long-term follow-up of a patient with hepatocellular carcinoma associated with triple hepatitis virus (HBV, HDV, HCV) infection.

A 69-year-old Japanese man with hepatocellular carcinoma (HCC) associated with triple hepatitis viruses [hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV)] infection is reported. The patient had a past history of intravenous drug abuse and a tattoo on his back. A liver biopsy, performed in November 1989, showed HCC associated with cirrhosis. HBsAg and anti-HD antibody had been detected repeatedly starting in August 1984 and anti-HCV antibody was detected in 1990. By indirect immunoperoxidase staining the HD antigen was detected in the nuclei of hepatocytes of biopsy specimens and noncancerous liver cells obtained from autopsy specimens. Liver cirrhosis associated with triple hepatitis virus infection developed to hepatocellular carcinoma, and transcatheter arterial embolization treatment for HCC was effective. Despite having HCC and cirrhosis, the patient lived well beyond the expected time.

Aged↗

Two proline-rich nuclear localization signals in the amino- and carboxyl-terminal regions of the Borna disease virus phosphoprotein.

Borna disease virus (BDV) uses a unique strategy of replication and transcription which takes place in the nucleus, unlike other known, nonsegmented, negative-stranded RNA viruses of animal origin. In this process, viral constituents necessary for replication must be transported to the nucleus from the cytoplasm. We report here the evidence that BDV P protein, which may play an important role in viral replication and transcription, is transported into the nucleus in the absence of other viral constituents. This transportation is accomplished by its own nuclear localization signals (NLSs), which are present in both N-terminal (29PRPRKIPR36) and C-terminal (181PPRIYPQLPSAPT193) regions of the protein. These two NLSs can function independently and both have several Pro residues as key amino acids.

Amino Acid Sequence↗

A novel Rab GTPase, Rab33B, is ubiquitously expressed and localized to the medial Golgi cisternae.

Small GTP-binding proteins of the Rab family play important roles at defined steps of vesicular transport in protein secretion and the endocytosis pathway. In mammals, more than 30 proteins belonging to the Rab family have been reported to date. We report here the molecular cloning and characterization of a novel Rab protein, Rab33B. The amino acid sequence of Rab33B shows 55.3% identity to the Rab33A protein (previously called S10), and these two proteins share unique amino acid sequences at the effector domain. The genomic organization of rab33B was the same as rab33A: it consists of two exons. Thus, these two proteins make a subclass within the Rab family. Northern blot analysis showed that rab33B is expressed ubiquitously in mouse tissues, in contrast to rab33A whose expression is restricted to the brain and the immune system. A 26 kDa protein was detected by western blotting using a Rab33B-specific monoclonal antibody. Using immunofluorescence studies, Rab33B was shown to co-localize with (alpha)-mannosidase II, a Golgi-specific marker. Immunoelectron microscopy analysis further defined the localization of Rab33B to the medial Golgi cisternae. These results suggest Rab33B plays a role in intra-Golgi transport.

Animals↗

Structure and expression of the mouse S10 gene.

We previously reported the cloning of a human S10 cDNA which encodes a small GTP-binding protein belonging to the Rab subfamily. Here we describe a mouse S10 cDNA and its genomic structure. Mouse S10 is 92.3% homologous at the nucleotide level and 98.3% identical at the amino acid level compared to human S10. The mouse S10 gene is comprised of two exons and a single intron. Northern blotting of tissue RNAs indicates that the S10 gene is predominantly expressed in brain.

Amino Acid Sequence↗

Amplification of a full-length Borna disease virus (BDV) cDNA from total RNA of cells persistently infected with BDV.

We have developed a novel reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify the full-length 8.9 kilobase (kbp) cDNA of the Borna disease virus (BDV) RNA genome from the total cellular RNA of MDCK cells persistently infected with BDV (MDCK/BDV). Antigenomic BDV cDNA was reverse transcribed using a 53-mer oligonucleotide primer, corresponding to the 5'-terminus of a putative 3'-leader sequence of the BDV RNA genome, for 2 hr at 42 C followed by 30 min at 55 C. PCR was performed in the presence of this 53-mer antigenomic primer and a 25-mer primer, corresponding to the 3'-terminus of the BDV antigenomic cDNA, by use of an rTth DNA polymerase with proof-reading activity. The amplified full-length BDV cDNA was detected in as little as 20 ng of total cellular RNA of MDCK/BDV. This RT-PCR method should be a useful technique to study the molecular quasispecies of BDV.

Animals↗

Hepatitis C transmission between spouses.

To examine inter-spouse transmission as one of the potential routes of infection for hepatitis C virus (HCV), 121 patients with HCV-related chronic liver disease who tested positive for antibodies to HCV (anti-HCV) and their spouses were studied. Of these, 21 (17.4%) patients had spouses with anti-HCV. In 12 couples, the HCV genotype matched (type II: 10 couples, type III: two couples). The genotype differed in six couples. One patient was positive for anti-HCV, but negative for HCV-RNA, while the spouse was positive for both. The remaining two couples were only positive for anti-HCV. Genetic heterogeneity in the hypervariable region 1 of HCV was analysed in 11 couples with matched genotypes. In two couples, no mutation was recognized in the putative E2/NS1 genes using the heteroduplex method. The present study provides evidence to verify household transmission of HCV between patients and their spouses. These results suggest that inter-spouse transmission may be a potential route of transmission of HCV infection. However, other environmental factors (e.g. the duration of the marriage) cannot be ignored.

Adult↗