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Hideki Adachi

Publications and source records attributed to Hideki Adachi.

At least 19 recordsLinked to original sources
PubMed2006

Role of scavenger receptors in the binding and internalization of heat shock protein 70.

Extracellular heat shock protein 70 (Hsp70) exerts profound effects both in mediating tumor rejection by Hsp70-based vaccines and in autoimmunity. Further progress in this area, however, awaits the identification of the cell surface receptors for extracellular Hsp70 that mediate its immune functions. We have examined a wide range of candidate Hsp70 receptors and find significant binding through two main families of cell surface proteins, including 1) the scavenger receptor (SR) family and 2) C-type lectins of the NK family. In addition, given that the anticancer effects of Hsp70 vaccines have been shown to involve uptake of Ags by APC exposed to Hsp70-tumor Ag complexes, we have examined the ability of the receptors identified here to internalize Hsp70-peptide complexes. Our findings indicate that three members of the SR family (lectin-like oxidized low density lipoprotein receptor 1; fasciclin, epidermal growth factor-like, laminin-type epidermal growth factor-like, and link domain-containing scavenger receptor-1; and SR expressed by endothelial cells-1) are able to bind Hsp70-peptide complexes and mediate its efficient internalization. Indeed, each of the SR was able to mediate efficient uptake of Hsp70 when transfected into Chinese hamster ovary cells previously null for uptake. Curiously, Hsp70 internalization occurs independently of the intracellular domains of the SR, and Hsp70 uptake could be detected when the entire intracellular domain of lectin-like oxidized low density lipoprotein receptor 1 or SR expressed by endothelial cells-1 was truncated. The existence of a wide repertoire of cell surface Hsp70-binding structures may permit intracellular responses to extracellular Hsp70 that are cell specific and discriminate between Hsp70 family members.

Animals↗
PubMed2006

Endothelial scavenger receptors.

In the past few decades, cDNAs for endothelial scavenger receptors that bind to negatively charged molecules, particularly acetylated low density lipoproteins (Ac-LDL), have been cloned by expression cloning using modified LDL as ligands. A prototypic members of endothelial scavenger receptor family, namely, scavenger receptor class B type I (SR-BI) has been characterized as a high density lipoprotein (HDL) receptor. Another prototypic member, CD36, has been determined as a multiple ligand receptor because it binds to oxidized LDLs (Ox-LDL), trombospondin, erythrocytes infected with Plasmodium falciparum, long-chain fatty acids, and Gram-negative and Gram-positive bacteria. Lectin-like oxidized LDL receptor-1 (LOX-1) has been discovered as the principal receptor that mediates the action of Ox-LDL in the vascular walls. Recently, the structure of oxidized phospholipids, originally found in Ox-LDL, and its molecular mechanism of action on endothelial cells were determined. Further, the use of genetically manipulated rodent models and the recent forward genetic screening technique revealed the physiological and pathological functions of these endothelial scavenger receptors in innate immunity and infection. In this review, the structure and function of these multiligand scavenger receptors of endothelial cells have been described mainly in relation with lipid metabolism.

Animals↗
PubMed2006

[A case of AIDS-complicated lung infection mimicking acute eosinophilic pneumonia].

A 34-year-old man was admitted with dyspnea and low grade fever. Chest radiograph and computed tomography (CT) showed bilateral, ground glass opacities and perihilar consolidation. Bronchoalveolar lavage (BAL) was performed. The percentage of eosinophils in the BAL fluid (BALF) was elevated (20.5%). BALF smear and culture showed normal flora. Acute eosinophilic pneumonia was diagnosed and steroid therapy was performed. Afterwards he was transferred to our hospital. The HIV antibody was positive and peripheral blood CD-4 positive lymphocytes decreased to 10/microl, cytomegalovirus (CMV) antigenemia was positive and beta-D-glucan increased. CMV infection and pneumocystis pneumonia (PCP) complicated with AIDS was diagnosed. Trimethoprim/sulfamethoxazole, ganciclovir, and antifungal drugs were administered, but he suffered pneumothorax on the 18th day after admission and died. Histopathologic findings from an autopsy lung specimen revealed CMV infection and PCP. It is known that the percentage of eosinophils in the BALF increases in some cases of PCP complicated with AIDS. We emphasize that it is necessary to consider PCP when the percentage of eosinophils in the BALF increase.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Type F scavenger receptor SREC-I interacts with advillin, a member of the gelsolin/villin family, and induces neurite-like outgrowth.

The scavenger receptor expressed by endothelial cells (SREC) was isolated from a human endothelial cell line and consists of two isoforms named SREC-I and -II. Both isoforms have no significant homology to other types of scavenger receptors. They contain 10 repeats of epidermal growth factor-like cysteine-rich motifs in the extracellular domains and have unusually long C-terminal cytoplasmic domains with Ser/Pro-rich regions. The extracellular domain of SREC-I binds modified low density lipoprotein and mediates a homophilic SREC-I/SREC-I or heterophilic SREC-I/SREC-II trans-interaction. However, the significance of large Ser/Pro-rich cytoplasmic domains of SRECs is not clear. Here, we found that when SREC-I was overexpressed in murine fibroblastic L cells, neurite-like outgrowth was induced, indicating that the receptor can lead to changes in cell morphology. The SREC-I-mediated morphological change required the cytoplasmic domain of the protein, and we identified advillin, a member of the gelsolin/villin family of actin regulatory proteins, as a protein binding to this domain. Reduction of advillin expression in L cells by RNAi led to the absence of the described SREC-I-induced morphological changes, indicating that advillin is a prerequisite for the change. Finally, we demonstrated that SREC-I and advillin were co-expressed and interacted with each other in dorsal root ganglion neurons during embryonic development and that overexpression of both SREC-I and advillin in cultured Neuro-2a cells induced long process formation. These results suggest that the interaction of SREC-I and advillin are involved in the development of dorsal root ganglion neurons by inducing the described morphological changes.

Amino Acid Sequence↗
PubMed2004

Scavenger receptor expressed by endothelial cells I (SREC-I) mediates the uptake of acetylated low density lipoproteins by macrophages stimulated with lipopolysaccharide.

Scavenger receptor expressed by endothelial cells I (SREC-I) is a novel endocytic receptor for acetylated low density lipoprotein (LDL). Here we show that SREC-I is expressed in a wide variety of tissues, including macrophages and aortas. Lipopolysaccharide (LPS) robustly stimulated the expression of SREC-I in macrophages. In an initial attempt to clarify the role of SREC-I in the uptake of modified lipoproteins as well as in the development of atherosclerosis, we generated mice with a targeted disruption of the SREC-I gene by homologous recombination in embryonic stem cells. To exclude the overwhelming effect of the type A scavenger receptor (SR-A) on the uptake of Ac-LDL, we further generated mice lacking both SR-A and SREC-I (SR-A(-/-);SREC-I(-/-)) by cross-breeding and compared the uptake and degradation of Ac-LDL in the isolated macrophages. The contribution of SR-A and SREC-I to the overall degradation of Ac-LDL was 85 and 5%, respectively, in a non-stimulated condition. LPS increased the uptake and degradation of Ac-LDL by 1.8-fold. In this condition, the contribution of SR-A and SREC-I to the overall degradation of Ac-LDL was 90 and 6%, respectively. LPS increased the absolute contribution of SR-A and SREC-I by 1.9- and 2.3-fold, respectively. On the other hand, LPS decreased the absolute contribution of other pathways by 31%. Consistently, LPS did not increase the expression of other members of the scavenger receptor family such as CD36. In conclusion, SREC-I serves as a major endocytic receptor for Ac-LDL in LPS-stimulated macrophages lacking SR-A, suggesting that it has a key role in the development of atherosclerosis in concert with SR-A.

Amino Acid Sequence↗
PubMed2004

Primary seminoma in the middle mediastinum.

Primary mediastinal seminoma is a relatively rare tumor usually located in the anterior mediastinum. We report here an extremely rare case of a 66-year-old man with primary seminoma in the middle mediastinum. A physical examination showed lymphadenopathy in the right supraclavicular area. A chest CT confirmed the presence of a tumor occupying the retrotracheal space. A histological examination demonstrated metastatic seminoma from the open biopsy of the lymph node. Abdominal, pelvis, and cerebral CT scan and testicular ultrasound were negative. Thus, primary mediastinal seminoma in the middle mediastinum with supraclavicular lymph node metastasis was diagnosed.

Aged↗
PubMed2004

Subacute cor pulmonale due to tumor embolism.

We describe a patient wih subacute cor pulmonale caused by tumor emboli in the lungs. A 64-year-old female suffering from a subacute progressive cough and shortness of breathing died of severe pulmonary hypertension seven days after admission. Neither chest CT scans nor lung perfusion scintigraphy showed any abnormal findings. Microscopic examination after an autopsy revealed diffuse intravascular tumor emboli occluding not only the small pulmonary arteries and arterioles, but also the lymphatic vessels, which were suggested to be metastases of a breast carcinoma resected five years previously. Thus, pulmonary tumor embolism should be considered in the differential diagnosis of primary pulmonary hypertension, particularly in patients with a past history of cancers.

Autopsy↗
PubMed2004

[Lymphangioleiomyomatosis (LAM) causing chylothorax].

A 28-year-old woman was admitted to our hospital complaining of chest pain and dyspnea. Chest radiographs showed left pleural effusion. The effused fluid obtained by thoracocentesis was milky, and so chylothorax was diagnosed. A high-resolution chest CT (HRCT) scan demonstrated diffuse multiple cystic lesions, which were undetectable by conventional CT. An abdominal CT scan showed a retroperitoneal tumor. Since the effusion was resistant to conservative therapy, we performed clipping of the thoracic duct under the diaphragm. Since the effusion disappeared after continuous aspiration, 10 KE of OK-432 was administered into the pleural cavity, and the chylorrhea disappeared. The clinical diagnosis, based on the biopsy of the abdominal tumor, was lymphangioleiomyomatosis. Chylothorax developing from lymphangioleiomyomatosis is rare in Japan. However, we must consider the possibility of lymphangioleiomyomatosis in patients with chylothorax, and always perform chest HRCT.

Adult↗
PubMed2003

Crystal structure of a humanized Fab fragment of anti-tissue-factor antibody in complex with tissue factor.

Tissue factor (TF) is a membrane-anchored protein that initiates the extrinsic cascade of blood coagulation. TF forms a complex with serine protease Factor VIIa, and then activates Factor X zymogen to Factor Xa, leading to the blood coagulation. Humanized anti-TF antibody hATR-5 strongly inhibits TF-initiated blood coagulation, and is of potential use for various thrombotic diseases. The Fab fragment of antibody hATR-5 is obtained for crystallization. The crystal structure of the complex of the Fab with extracellular domains of human TF was determined with the molecular replacement method, and refined to an R factor of 0.196 at 2.1 A resolution. All the complementarity-determining regions (CDRs) of the Fab are involved in interaction with the C-terminal-side extracellular domain of TF through 19 hydrogen bonds. The interface between the Fab and TF molecules contains 15 water molecules, and yields buried surface areas as wide as 2000 A2. The TF surface in the interface is possibly involved in the activation of Factor X, by forming a transient ternary complex of Factor X-TF-Factor VIIa. Electrostatic interactions are predominantly observed between the heavy-chain CDRs and TF. These hydrogen-bonding and electrostatic interactions together with the wide buried areas contribute to the high affinity of the antibody toward TF, leading to the effective inhibition of the TF-initiated blood coagulation.

Antibodies↗
PubMed2003

Direct evidence of facilitative actions of dopamine in the medial preoptic area on reflexive and noncontact erections in male rats.

PURPOSE: We examined the effects of alterations of the extracellular dopamine level in the medial preoptic area on 2 erectile contexts, namely reflexive and noncontact erections, in male rats. MATERIALS AND METHODS: The extracellular dopamine level was measured in the medial preoptic area after administering the dopamine reuptake inhibitor bupropion hydrochloride (Sigma Chemical Co., St. Louis, Missouri) into the same area through a micro-dialysis tube. We measured the frequency and latency of reflexive erections, and the frequency of noncontact erection during infusion of bupropion. RESULTS: Administration of 10 mM. bupropion was associated with significant elevation in the extracellular dopamine level in the medial preoptic area. Bupropion (1 mM.) and Ringer's solution did not induce significant alterations in dopamine in the medial preoptic area. The number of reflexive erections significantly increased and erection latency decreased during infusion of 10 mM. bupropion into the medial preoptic area. The number of noncontact erections was also increased by administering 10 mM. of drug. CONCLUSIONS: The altered dopamine level in the medial preoptic area affected 2 distinct penile erectile contexts, suggesting that the dopamine levels in the medial preoptic area may be involved in the regulation of erection. These results may have important implications for the central regulation of penile erection.

Animals↗
PubMed2003

Evaluation of blood supply to the parathyroid glands in secondary hyperparathyroidism compared with histopathology.

BACKGROUND: In chronic renal failure patients, the parathyroid glands progress from diffuse hyperplasia to nodular hyperplasia, and it is important to distinguish between these as the latter form is more aggressive. This progress can be confirmed histologically, but the present study aimed to determine whether the different types of hyperplasia could be distinguished by power-Doppler ultrasonography (US). METHODS: Twenty-one consecutive renal failure patients were scheduled to undergo parathyroidectomy (PTx). Of 70 resected parathyroid glands, 63 were assessed by pre-operative power-Doppler US, classified into four groups based on the flow signal pattern and then correlated with the post-operative histopathology. RESULTS: With power-Doppler US imaging, 60.0% of glands without a signal inside the gland were diagnosed as diffuse hyperplasia or diffuse hyperplasia with early nodularity. Of glands with in-gland signals, 83.7% were nodular or had a single nodule typical of nodular hyperplasia. Even when the focus was on parathyroid glands weighing <or=0.5 g, similar results were obtained. CONCLUSIONS: Power-Doppler US imaging is a useful method for determining the pathological features of parathyroid glands and is recommended for selecting the most suitable therapy.

Female↗
PubMed2002

FEEL-1 and FEEL-2 are endocytic receptors for advanced glycation end products.

Advanced glycation end products (AGEs) are nonenzymatically glycosylated proteins, which accumulate in vascular tissues in aging and diabetes. Receptors for AGEs include scavenger receptors, which recognize acetylated low density lipoproteins (Ac-LDL) such as scavenger receptor class AI/AII (SR-A), cell surface glycoprotein CD36, scavenger receptor class B type I (SR-BI), and lectin-like oxidized low density lipoprotein receptor-1. The broad ligand repertoire of these receptors as well as the diversity of the receptors for AGEs have prompted us to examine whether AGEs are also recognized by the novel scavenger receptors, which we have recently isolated from a cDNA library prepared from human umbilical vein endothelial cells, such as the scavenger receptor expressed by endothelial cells-I (SREC-I); the fasciclin EGF-like, laminin-type EGF-like, and link domain-containing scavenger receptor-1 (FEEL-1); and its paralogous protein, FEEL-2. At 4 degrees C, (125)I-AGE-bovine serum albumin (BSA) exhibited high affinity specific binding to Chinese hamster ovary (CHO) cells overexpressing FEEL-1 (CHO-FEEL-1) and FEEL-2 (CHO-FEEL-2) with K(d) of 2.55 and 1.68 microg/ml, respectively, but not to CHO cells expressing SREC (CHO-SREC) and parent CHO cells. At 37 degrees C, (125)I-AGE-BSA was taken up and degraded by CHO-FEEL-1 and CHO-FEEL-2 cells but not by CHO-SREC and parent CHO cells. Thus, the ability to bind Ac-LDL is not necessarily a prerequisite to bind AGEs. The (125)I-AGE-BSA binding to CHO-FEEL-1 and CHO-FEEL-2 cells was effectively inhibited by Ac-LDL and polyanionic SR-A inhibitors such as fucoidan, polyinosinic acids, and dextran sulfate but not by native LDL, oxidized LDL, or HDL. FEEL-1, which is expressed by the liver and vascular tissues, may recognize AGEs, thereby contributing to the development of diabetic vascular complications and atherosclerosis.

Aged↗
PubMed2002

Crystal structure of human renal dipeptidase involved in beta-lactam hydrolysis.

Human renal dipeptidase is a membrane-bound glycoprotein hydrolyzing dipeptides and is involved in hydrolytic metabolism of penem and carbapenem beta-lactam antibiotics. The crystal structures of the saccharide-trimmed enzyme are determined as unliganded and inhibitor-liganded forms. They are informative for designing new antibiotics that are not hydrolyzed by this enzyme. The active site in each of the (alpha/beta)(8) barrel subunits of the homodimeric molecule is composed of binuclear zinc ions bridged by the Glu125 side-chain located at the bottom of the barrel, and it faces toward the microvillar membrane of a kidney tubule. A dipeptidyl moiety of the therapeutically used cilastatin inhibitor is fully accommodated in the active-site pocket, which is small enough for precise recognition of dipeptide substrates. The barrel and active-site architectures utilizing catalytic metal ions exhibit unexpected similarities to those of the murine adenosine deaminase and the catalytic domain of the bacterial urease.

Anti-Bacterial Agents↗
PubMed2002

SREC-II, a new member of the scavenger receptor type F family, trans-interacts with SREC-I through its extracellular domain.

The scavenger receptor expressed by endothelial cells (SREC) with an extremely large cytoplasmic domain, was originally identified in a human endothelial cell line. In this study, we have cloned a second isoform named SREC-II and shown that there is a heterophilic interaction between SREC-I and -II at their extracellular domains. The cDNA for murine SREC-II encodes an 834-amino acid protein with 35% homology to SREC-I. Similar to SREC-I, SREC-II contains multiple epidermal growth factor-like repeats in its extracellular domain. However, in contrast to SREC-I, SREC-II had little activity to internalize modified low density lipoproteins (LDL). A Northern blot analysis revealed a tissue expression pattern of SREC-II similar to that of SREC-I with predominant expression in human heart, lung, ovary, and placenta. Mouse fibroblast L cells with no tendency to associate showed noticeable aggregation when SREC-I was overexpressed in these cells, whereas overexpression of SREC-II caused only slight aggregation. Remarkably, intense aggregation was observed when SREC-I-expressing cells were mixed with those expressing SREC-II. Deletion of almost all of the cytoplasmic receptor domain had no effect on the receptor expression and cell aggregation, indicating that solely the extracellular domain is involved in cell aggregation. The association of SREC-I and -II was effectively suppressed by the presence of scavenger receptor ligands such as acetylated LDL and oxidized LDL. These findings suggest that SREC-I and -II show weak cell-cell interaction by their extracellular domains (termed homophilic trans-interaction) but display strong heterophilic trans-interaction through the extracellular epidermal growth factor-like repeat domains.

Amino Acid Sequence↗
PubMed2002

FEEL-1, a novel scavenger receptor with in vitro bacteria-binding and angiogenesis-modulating activities.

Employing the expression cloning technique, we cloned a novel scavenger receptor that is structurally unrelated to other scavenger receptors. The cloned receptor contained fasciclin (Fas-1), epidermal growth factor (EGF)-like, laminin-type EGF-like, and link domains. Based on the domain structures, we temporarily named it FEEL-1 (fasciclin, EGF-like, laminin-type EGF-like, and link domain-containing scavenger receptor-1). A data base search suggested the presence of a paralogous gene of FEEL-1, the full-length cDNA of this gene was also cloned, and its nucleotide sequence was determined. The deduced amino acid sequence of the clone indicated that its domain organization is similar to FEEL-1, and we named this clone FEEL-2. The effect of monoclonal antibodies against FEEL-1 indicated that FEEL-1 is the major receptor for 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbo-cyanine perchlorate (DiI)-labeled acetylated low density lipoprotein (DiI-Ac-LDL) in human umbilical vein endothelial cells. Reverse transcription and PCR analysis revealed that both FEEL-1 and FEEL-2 were expressed in several tissues and expressed highly in the spleen and lymph node. On the other hand, only FEEL-1 was expressed in mononuclear cells, particularly resting CD14(+) cells. The transient expression of FEEL-1 and FEEL-2 in Chinese hamster ovary cells demonstrated that both FEELs could bind to DiI-Ac-LDL. Both receptors were also found to bind to Gram-negative and Gram-positive bacteria. These results suggest that FEELs play important roles in the defense mechanisms against bacterial infection. Finally, the phenotypic effect of the inhibition of FEEL-1 on vascular remodeling was tested in vitro using the Matrigel tube formation assay, and we found a marked reduction in the degree of cell-cell interaction in anti-FEEL-1 monoclonal antibody-treated cells, suggesting the role of this receptor in angiogenesis.

Amino Acid Sequence↗
PubMed2002

Characterization of the human gene encoding the scavenger receptor expressed by endothelial cell and its regulation by a novel transcription factor, endothelial zinc finger protein-2.

The scavenger receptor expressed by endothelial cell (SREC), mediates the selective uptake of modified low density lipoprotein (LDL), such as acetylated LDL and oxidized LDL, into endothelial cells. The SREC gene spans 12 kilobase pairs and contains 11 exons. Analysis of full-length cDNA clones of SREC from a peripheral blood leukocyte cDNA library revealed that at least five alternatively spliced cDNAs were present, and two of them encoded soluble forms of SREC. The transcription start site of the SREC gene was mapped, and DNA sequence analysis revealed an Sp1 binding site in its proximal region. Deletion analysis of the 5'-flanking sequence revealed that sequence between base pairs -108 and -98 was critical for the promoter activity. This region contained half of an inverted repeat (IR) sequence with a triple nucleotide spacer (IR-3). A protected sequence between base pairs -268 and +17 was defined by in vitro DNase I footprinting analysis using human umbilical vein endothelial cell (HUVEC) nuclear extract. A novel transcription factor, endothelial zinc finger protein-2 (EZF-2), that binds to the 5'-flanking critical region of the SREC promoter activity was cloned from a HUVEC cDNA library employing a one-hybrid system. Whereas purified recombinant Sp1 alone produced similar protection in in vitro DNase I footprinting analysis, EZF-2 also bound to the 5'-flanking region SREC promoter. Co-transfection of SREC promoter and Sp1 or EZF-2 expression plasmids in HUVEC revealed that EZF-2 but not Sp1 increased SREC promoter activity. On the other hand, the mutation of either the Sp1 motif or IR-3 motif resulted in a decrease in the promoter activity. These results suggest that whereas Sp1 is the major nuclear protein bound to the regulatory region of the promoter, both EZF-2 and Sp1 are responsible for its regulation.

Amino Acid Sequence↗
PubMed2002

Does transurethral resection of the prostate facilitate detection of clinically significant prostate cancer that is missed with systematic sextant and transition zone biopsies?

BACKGROUND: A prospective study was conducted to determine whether transurethral resection of the prostate (TURP) facilitates detection of prostate cancer that is missed with systematic sextant biopsies associated with transition zone (TZ) biopsies. METHODS: A total of 139 consecutive patients underwent transperineal TZ biopsies of each lobe in addition to a transrectal systematic sextant peripheral zone (PZ) biopsy. Patients whose biopsies were negative for cancer received TURP for relief of lower urinary tract obstruction when indicated. RESULTS: Cancer was detected in biopsy specimens of 40 patients. Of these cancers, 18 originated in the PZ alone and 22 were located both in the TZ and the PZ. No cancers were detected in the TZ alone. Of 99 patients who were proven not to have cancer by the biopsies, 18 were indicated for TURP. Five of these patients (28%) had cancer in the resected tissues. All cancers were clinically organ confined and their Gleason sum scores were 2-5. Cancer-positive chips accounted for less than 10% of all resected specimens. Of the 66 patients with negative biopsies and without indication for TURP, four (6%) were revealed to have an elevation of the serum PSA level during follow up. They were later proven to have cancer by a second biopsy. CONCLUSION: Routine use of TZ biopsy is not warranted for detection of cancer. Transurethral resection of the prostate can detect cancers in patients with negative PZ and TZ biopsies. However, cancers detected by TURP may not always be clinically significant and only four of 66 patients who were not indicated for TURP and received a close follow up were later found to have cancer, although their follow-up period was short. Thus, it still remains to be elucidated whether TURP is necessary for all patients with negative biopsies of the prostate.

Aged↗