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K Inaba

Publications and source records attributed to K Inaba.

At least 19 recordsLinked to original sources
PubMed2001

Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo.

Dendritic cells (DCs) have the capacity to initiate immune responses, but it has been postulated that they may also be involved in inducing peripheral tolerance. To examine the function of DCs in the steady state we devised an antigen delivery system targeting these specialized antigen presenting cells in vivo using a monoclonal antibody to a DC-restricted endocytic receptor, DEC-205. Our experiments show that this route of antigen delivery to DCs is several orders of magnitude more efficient than free peptide in complete Freund's adjuvant (CFA) in inducing T cell activation and cell division. However, T cells activated by antigen delivered to DCs are not polarized to produce T helper type 1 cytokine interferon gamma and the activation response is not sustained. Within 7 d the number of antigen-specific T cells is severely reduced, and the residual T cells become unresponsive to systemic challenge with antigen in CFA. Coinjection of the DC-targeted antigen and anti-CD40 agonistic antibody changes the outcome from tolerance to prolonged T cell activation and immunity. We conclude that in the absence of additional stimuli DCs induce transient antigen-specific T cell activation followed by T cell deletion and unresponsiveness.

Animals↗
PubMed2001

Molecular cloning and characterization of a thioredoxin/nucleoside diphosphate kinase related dynein intermediate chain from the ascidian, Ciona intestinalis.

Flagellar outer arm dynein from the ascidian, Ciona intestinalis, contains five intermediate chains (IC1-5). Molecular cloning of C. intestinalis IC3 shows significant sequence homology to the dynein intermediate chain (IC1) from sea urchin and human NM23-H8 protein. The N-terminal thioredoxin-related region is well conserved in the C. intestinalis IC3, sea urchin IC1, and human NM23-H8 protein. Three NDP kinase (NDPK)-related sequences are present in middle portions of both C. intestinalis IC3 and sea urchin IC1, but the human NM23-H8 protein had only two. A large part of the C-terminal glutamic acid-rich region present in sea urchin IC1 was greatly reduced in C. intestinalis IC3 and completely lost in human NM23-H8. Thus, thioredoxin/NDPK-related dynein intermediate chains (TNDK-DIC) would be a characteristic of metazoan flagella and they have become smaller in size and less acidic during evolution.

Amino Acid Sequence↗
PubMed2001

Differential regulation of human blood dendritic cell subsets by IFNs.

Based on the relative expression of CD11c and CD1a, we previously identified subsets of dendritic cells (DCs) or DC precursors in human peripheral blood. A CD1a(+)/CD11c(+) population (CD11c(+) DCs), also called myeloid DCs, is an immediate precursor of Langerhans cells, whereas a CD1a(-)/CD11c(-) population (CD11c(-) DCs), sometimes called lymphoid DCs but better known as plasmacytoid DCs, is composed of type I IFN (IFN-alpha beta)-producing cells. Here, we investigate the effects of IFN-alpha beta and IFN-gamma as well as other cytokines on CD11c(+) and CD11c(-) DC subsets, directly isolated from the peripheral blood, instead of in vitro-generated DCs. IFN-gamma and IFN-alpha, rather than GM-CSF, were the most potent cytokines for enhancing the maturation of CD11c(+) DCs. Incubation of CD11c(+) DCs with IFN-gamma also resulted in increased IL-12 production, and this IL-12 allowed DCs to increase Th1 responses by alloreactive T cells. In contrast, IFN-alpha did not induce IL-12 but, rather, augmented IL-10 production. IFN-alpha-primed matured CD11c(+) DCs induced IL-10-producing regulatory T cells; however, this process was independent of the DC-derived IL-10. On the other hand, IFN-alpha by itself neither matured CD11c(-) DCs nor altered the polarization of responding T cells, although this cytokine was a potent survival factor for CD11c(-) DCs. Unlike IFN-alpha, IL-3 was a potent survival factor and induced the maturation of CD11c(-) DCs. The IL-3-primed CD11c(-) DCs activated T cells to produce IL-10, IFN-gamma, and IL-4. Thus, CD11c(+) and CD11c(-) DC subsets play distinct roles in the cytokine network, especially their responses to IFNs.

Cell Differentiation↗
PubMed2001

T cell studies in a peptide-induced model of systemic lupus erythematosus.

We have previously reported that immunization with a peptide mimetope of dsDNA on a branched polylysine backbone (DWEYSVWLSN-MAP) induces a systemic lupus erythematosus-like syndrome in the nonautoimmune BALB/c mouse strain. To understand the mechanism underlying this breakdown in self tolerance, we examined the role of T cells in the response. Our results show that the anti-foreign and anti-self response induced by immunization is T cell dependent and is mediated by I-E(d)-restricted CD4(+) T cells of the Th1 subset. In addition, generation of the critical T cell epitope requires processing by APCs and depends on the presence of both DWEYSVWLSN and the MAP backbone. The breakdown in self tolerance does not occur through cross-reactivity between the T cell epitope of DWEYSVWLSN-MAP and epitopes derived from nuclear Ags. In this induced-model of SLE, therefore, autoreactivity results from the activation of T cells specific for foreign Ag and of cross-reactive anti-foreign, anti-self B cells. Despite the fact that tissue injury is mediated by Ab, the critical initiating T cell response is Th1.

Animals↗
PubMed2001

Intrahepatic cholangiojejunostomy for unresectable malignant biliary tumors with obstructive jaundice.

We reviewed our experience with intrahepatic cholangiojejunostomy as a palliative therapy for patients with unresectable malignant diseases involving the ductal confluence or the common hepatic duct. Fifteen patients with malignant biliary obstruction were treated by cholangiojejunostomy at our hospital. Two patients had intrahepatic cholangiocarcinoma, 7 had gallbladder carcinoma, 5 had bile duct carcionoma, and 1 had pancreatic carcinoma. Segment III cholangiojejunostomies were performed in 14 patients and segment V cholangiojejunostomy in 1. Contraindications for surgical resection were locoregional invasion of tumors involving the proper and/or common hepatic artery and portal vein in 15 patients and the presence of hepatic metastases in 6 patients. Liver metastases were detected in 5 of the 7 patients with gallbladder carcinoma. Postoperative complications occurred in 2 patients (13%), but there was no leakage of the cholangioenteric anastomosis in our series. There was no operative mortality after cholangiojejunostomy. Of the 9 patients who survived for more than 6 months after surgery, 7 showed a significant improvement in performance status (PS) (82 +/- 10%) 3 months after the surgery compared with the preoperative PS (70 +/- 7%). Four of the 9 patients had recurrent cholangitis as a late complication, but 4 were completely free from jaundice. Median survival after cholangioenteric bypass was 9 months (range, 2-25 months). With respect to tumor location, the median survival time was 4 months (range, 2-25 months) in patients with gallbladder carcinoma and 15.5 months (range, 12-22 months) in those with bile duct carcinoma. While the median survival period after surgery was only 3 months (range, 2 to 8 months) in the 5 patients with hepatic metastases from gallbladder carcinoma, 2 patients without liver metastasis survived for 9 and 25 months after segment III cholangioenteric bypass. In conclusion, cholangiojejunostomy can provide useful palliation for malignant biliary obstruction when combined with careful patient selection.

Bile Duct Neoplasms↗
PubMed2001

Blunt abdominal aortic trauma in association with thoracolumbar spine fractures.

All patients with blunt abdominal aortic disruption (BAAD) in the trauma registries at the three Regional Trauma Centres were retrospectively reviewed over the last decade. From the 11465 trauma admissions ISS>16,194 sustained aortic injuries. Eight cases of BAAD were identified, six with concurrent thoracolumbar spine (TLS) fractures (mean ISS 42). Patients with BAAD and TLS were subject to a detailed analysis. Clinically, three injury types were seen, hemodynamically unstable (uncontained full thickness laceration), stable symptomatic (intimal dissection with occlusion), and stable asymptomatic (contained full thickness laceration or intimal dissection without occlusion). All spinal column fractures involved a distractive mechanism, one with both distractive and translational fracture components. We propose that a distractive force, applied to the aorta lying anterior to the anterior longitudinal ligament, results in an aortic injury spectrum ranging from an intimal tear to a full thickness laceration, as a related injury. Computed tomography (CT) was an important imaging modality in the stable asymptomatic patients. All intimal dissections without occlusion were managed non-operatively. With distractive TLS fractures, BAAD needs to be considered.

Abdominal Injuries↗
PubMed2001

Characteristics of aneurysms arising from the horizontal portion of the anterior cerebral artery.

BACKGROUND: Aneurysms arising from the proximal portion of the anterior cerebral artery (A1: horizontal portion) are quite rare and are considered to be unique, because they are usually connected with other vascular anomalies and are sometimes part of a multiple aneurysm occurrence. A1 aneurysm cases experienced over the past seven and a half years are summarized in this paper. METHODS: A total of 413 patients were surgically treated including 142 patients with subarachnoid hemorrhage (SAH); the remaining 271 patients had unruptured aneurysms. Among them, nine cases were categorized as constituent A1 aneurysms, three with SAH and six with unruptured aneurysms. RESULTS: The shape of the aneurysm was saccular in all nine cases. Three of the nine cases had associated vascular malformations. The average aneurysm diameter in the three cases with SAH was 4.0 mm, which is smaller than other common aneurysms presenting with SAH. Eight aneurysms developed at the takeoff point of perforating arteries-the medial lenticulostriate artery in five cases and the recurrent artery of Heubner in three cases. In the remaining case, the aneurysm originated from the proximal end of the associated A1 fenestration. All nine patients had an excellent outcome after surgery. CONCLUSION: A1 aneurysms require surgical elimination even if they are small. We emphasize the importance of preserving the blood flow of these perforating arteries by avoiding compression with either the clip blade or the clip body itself.

Adult↗
PubMed2001

Five mouse homologues of the human dendritic cell C-type lectin, DC-SIGN.

DC-SIGN, a human C-type lectin, is expressed on the surface of dendritic cells (DC), while a closely related human gene, DC-SIGNR or L-SIGN, is found on sinusoidal endothelial cells of liver and lymph node. Both DC-SIGN and DC-SIGNR/L-SIGN can bind ICAM-3 and HIV gp120, and transmit HIV to susceptible cells in trans. Here, we report the cloning of five mouse genes homologous to human DC-SIGN and DC-SIGNR/L-SIGN. Only one gene, named mouse DC-SIGN, is highly expressed in DC, and is not found in a panel of mouse macrophage and lymphocyte cell lines. The other four genes, named mouse SIGNR1 (SIGN-Related gene 1), SIGNR2, SIGNR3 and SIGNR4, are expressed at lower levels in various cells according to RT-PCR and Northern blot analyses on RNA. All the genes of mouse DC-SIGN and SIGNRs map to adjacent regions of chromosome 8 A1.2-1.3. However, like human DC-SIGN, only the mouse DC-SIGN gene is closely juxtaposed to the CD23 gene, while the other four SIGNR genes are located close to each other in a neighboring region. mRNAs of mouse DC-SIGN and three SIGNR genes encode type II transmembrane proteins (DC-SIGN, 238 amino acids; SIGNR1, 325 amino acids; SIGNR3, 237 amino acids; SIGNR4, 208 amino acids), but the SIGNR2 gene only encodes a carbohydrate recognition domain (CRD) without a cytosolic domain and a transmembrane domain (SIGNR2, 178 amino acids). Amino acid sequence similarities between the CRD of human DC-SIGN and the mouse homologues are 67% for DC-SIGN, 69% for SIGNR1, 65% for SIGNR2, 68% for SIGNR3 and 70% for SIGNR4 respectively. However, the membrane proximal neck domains in the mouse genes are much shorter than their counterparts in human DC-SIGN and DC-SIGNR/L-SIGN. This family of mouse C-type lectins is therefore complex, but only one of the new genes, DC-SIGN, is juxtaposed to CD23 and is expressed at high levels in DC.

Amino Acid Sequence↗
PubMed2001

Skin antigens in the steady state are trafficked to regional lymph nodes by transforming growth factor-beta1-dependent cells.

Antigen capturing in the skin and antigen trafficking into regional lymph nodes (LN) initiate immune responses. In this study, employing melanin granule (MG) as an easily traceable antigen in two mouse strains that carried steel factor or hepatocyte growth factor transgenes and had melanocytosis in the epidermis or in the dermis respectively, we investigated the mechanism of antigen trafficking from the skin. MG captured in the epidermis or dermis accumulated in the regional LN, but not other tissues. Only in alymphoplastic mice did MG-laden cells pass through the lymphatics and reached many tissues. Since inflammatory regions were not observed in the skin of either type of transgenic mouse, our developmental system enables us to investigate constitutive capturing and trafficking of insoluble antigens in the steady state. Both dendritic cells and macrophages were laden with MG in the regional LN. To determine which cells traffic antigens to the LN, we prepared double mutants that carried the transgenes and lacked transforming growth factor (TGF)-beta1, since mice lacking TGF-beta1 are reported to be deficient of Langerhans cells. Few MG were observed in the regional LN of these double-mutant mice. We also showed that signaling via macrophage colony stimulating factor receptor or Flt3/Flk2 is not essential for development of the cells for this antigen trafficking. These results indicate that antigens in the epidermis and dermis in the steady state are trafficked into regional LN only by TGF-beta1-dependent cells, which may be a dendritic cell lineage.

Animals↗
PubMed2001

New method for obliterative treatment of an anterior wall aneurysm in the internal carotid artery: encircling silicone sheet clip procedure--technical case report.

OBJECTIVE AND IMPORTANCE: Aneurysms on the anterior surface of the internal carotid artery (ICA) have been shown to be somewhat different from ordinary berry aneurysms because they are rather small, grow rapidly in a short time, and easily lead to rupture, especially during surgery. The most difficult problem is that this type of aneurysm cannot be eliminated easily by an ordinary clipping procedure without causing apparent arterial stenosis or occlusion. CLINICAL PRESENTATION: A 52-year-old man experienced a subarachnoid hemorrhage because of a ruptured aneurysm located on the anterior surface of the ICA. The tiny aneurysmal body, which was covered with a layer of brain tissue, was successfully exposed. The ICA seemed to be atherosclerotic, and the aneurysmal portion was solitary and had a reddish color. TECHNIQUE: A large silicone sheet encircling clip (Vascwrap; Mizuho Ikakogyo Co., Ltd., Tokyo, Japan) was selected for this patient. The proximal margin of the silicone sheet was incised with a V-shaped cut, and the middle part of the sheet, which covered the diagonal part of the ICA, was trimmed to make it shorter. The blade of the fenestrated clip was applied to obliterate the aneurysm and was attached to the normal arterial wall together with this modified Vascwrap sheet to create a small space between the normal arterial wall and the surrounding Vascwrap sheet. Then tiny pieces of Teflon fiber (E.I. duPont de Nemours and Co., Wilmington, DE) was inserted from both margins, and the whole Vascwrap sheet was sealed with fibrin glue to ensure good adhesion. CONCLUSION: This method seemed adequate in treating this difficult aneurysm without causing postoperative regrowth or occlusion of the patient's ICA.

Carotid Artery, Internal↗
PubMed2001

Hypervascular liver metastasis from hypovascular ductal cell carcinoma of the pancreas.

In a case of hypervascular metastatic liver tumor, the vascularity of primary focus, pancreatic carcinoma was hypovascular. Based on the imaging findings, we thought before the operation that the two lesions were double cancers. Histological examination showed that the stromal volume of metastatic tumorous tissue was richer than that of the primary focus. It was suggested that the difference in the stromal volume was related to the difference of the vascularity. Some foctors originating in stromal cells might be involved in angiogenesis.

Carcinoma, Pancreatic Ductal↗
PubMed2001

Brain hypothermia relieves severe brain swelling following acute major cerebral artery occlusion.

Seven patients were treated with brain hypothermia following acute major cerebral artery occlusion to utilize the suppressive effect against brain swelling. Five patients had internal carotid and two had proximal middle cerebral artery occlusion. Except for the first two cases, hypothermia was introduced early and the temperature reached 35.0 degrees C within 6 hours after the onset. The core temperature finally stabilized between 32 degrees C to 34 degrees C. Hypothermia had a suppressive effect against brain swelling and the temperature showed a significant correlation to intracranial pressure. Recurrence of brain swelling was observed during the rewarming process, but two patients became independent and three patients were moderately disabled in wheelchairs. Only two patients died. Brain hypothermia is an effective treatment for acute major cerebral artery occlusion through the relief of brain swelling. The overall outcome may be improved by combining brain hypothermia with other conventional therapies such as osmotherapy and external decompression implemented with an extended period of rewarming.

Acute Disease↗
PubMed2000

Conversion of two-state to multi-state folding kinetics on fusion of two protein foldons.

Chymotrypsin inhibitor 2 (CI2) is the archetypal single-foldon protein that folds in simple two-state kinetics without the accumulation of a folding intermediate. To model the effects of fusion of single foldons to give a multi-foldon protein, we engineered a "double-CI2" protein, in which another CI2 polypeptide was inserted into the loop region of the parent CI2. CD and HSQC spectra demonstrated that while the double-CI2 protein adopted two kinds of native conformations, CI2-like structure was almost preserved in both the domains of double-CI2. In the folding kinetic studies, double-CI2 exhibited a remarkable rollover of the observed folding rates at low denaturant concentrations, indicating that double-CI2 accumulated a kinetic folding intermediate. The different folding mechanisms between WT-CI2 and double-CI2 support the present view that protein size or number of domains is an important determinant for formation of folding intermediates.

Amino Acid Sequence↗
PubMed2000

Substitution of the heme binding module in hemoglobin alpha- and beta-subunits. Implication for different regulation mechanisms of the heme proximal structure between hemoglobin and myoglobin.

In our previous work, we demonstrated that the replacement of the "heme binding module," a segment from F1 to G5 site, in myoglobin with that of hemoglobin alpha-subunit converted the heme proximal structure of myoglobin into the alpha-subunit type (Inaba, K., Ishimori, K. and Morishima, I. (1998) J. Mol. Biol. 283, 311-327). To further examine the structural regulation by the heme binding module in hemoglobin, we synthesized the betaalpha(HBM)-subunit, in which the heme binding module (HBM) of hemoglobin beta-subunit was replaced by that of hemoglobin alpha-subunit. Based on the gel chromatography, the betaalpha(HBM)-subunit was preferentially associated with the alpha-subunit to form a heterotetramer, alpha(2)[betaalpha(HBM)(2)], just as is native beta-subunit. Deoxy-alpha(2)[betaalpha(HBM)(2)] tetramer exhibited the hyperfine-shifted NMR resonance from the proximal histidyl N(delta)H proton and the resonance Raman band from the Fe-His vibrational mode at the same positions as native hemoglobin. Also, NMR spectra of carbonmonoxy and cyanomet alpha(2)[betaalpha(HBM)(2)] tetramer were quite similar to those of native hemoglobin. Consequently, the heme environmental structure of the betaalpha(HBM)-subunit in tetrameric alpha(2)[betaalpha(HBM)(2)] was similar to that of the beta-subunit in native tetrameric Hb A, and the structural conversion by the module substitution was not clear in the hemoglobin subunits. The contrastive structural effects of the module substitution on myoglobin and hemoglobin subunits strongly suggest different regulation mechanisms of the heme proximal structure between these two globins. Whereas the heme proximal structure of monomeric myoglobin is simply determined by the amino acid sequence of the heme binding module, that of tetrameric hemoglobin appears to be closely coupled to the subunit interactions.

Chromatography, Gel↗
PubMed2000

Transport of peptide-MHC class II complexes in developing dendritic cells.

Major histocompatibility complex class II (MHC II) molecules capture peptides within the endocytic pathway to generate T cell receptor (TCR) ligands. Immature dendritic cells (DCs) sequester intact antigens in lysosomes, processing and converting antigens into peptide-MHC II complexes upon induction of DC maturation. The complexes then accumulate in distinctive, nonlysosomal MHC II+ vesicles that appear to migrate to the cell surface. Although the vesicles exclude soluble lysosomal contents and antigen-processing machinery, many contain MHC I and B7 costimulatory molecules. After arrival at the cell surface, the MHC and costimulatory molecules remain clustered. Thus, transport of peptide-MHC II complexes by DCs not only accomplishes transfer from late endocytic compartments to the plasma membrane, but does so in a manner that selectively concentrates TCR ligands and costimulatory molecules for T cell contact.

Animals↗
PubMed2000

The formation of immunogenic major histocompatibility complex class II-peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli.

During their final differentiation or maturation, dendritic cells (DCs) redistribute their major histocompatibility complex (MHC) class II products from intracellular compartments to the plasma membrane. Using cells arrested in the immature state, we now find that DCs also regulate the initial intracellular formation of immunogenic MHC class II-peptide complexes. Immature DCs internalize the protein antigen, hen egg lysozyme (HEL), into late endosomes and lysosomes rich in MHC class II molecules. There, despite extensive colocalization of HEL protein and MHC class II products, MHC class II-peptide complexes do not form unless the DCs are exposed to inflammatory mediators such as tumor necrosis factor alpha, CD40 ligand, or lipoplolysaccharide. The control of T cell receptor (TCR) ligand formation was observed using the C4H3 monoclonal antibody to detect MHC class II-HEL peptide complexes by flow cytometry and confocal microscopy, and with HEL-specific 3A9 transgenic T cells to detect downregulation of the TCR upon MHC-peptide encounter. Even the binding of preprocessed HEL peptide to MHC class II is blocked in immature DCs, including the formation of C4H3 epitope in MHC class II compartments, suggesting an arrest to antigen presentation at the peptide-loading step, rather than an enhanced degradation of MHC class II-peptide complexes at the cell surface, as described in previous work. Therefore, the capacity of late endosomes and lysosomes to produce MHC class II-peptide complexes can be strictly controlled during DC differentiation, helping to coordinate antigen acquisition and inflammatory stimuli with formation of TCR ligands. The increased ability of maturing DCs to load MHC class II molecules with antigenic cargo contributes to the >100-fold enhancement of the subsequent primary immune response observed when immature and mature DCs are compared as immune adjuvants in culture and in mice.

Animals↗