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Biomedical subjects

N Araki

Publications and source records attributed to N Araki.

At least 55 records · Page 3Linked to original sources
PubMed1999

A novel NE-dlg/SAP102-associated protein, p51-nedasin, related to the amidohydrolase superfamily, interferes with the association between NE-dlg/SAP102 and N-methyl-D-aspartate receptor.

The membrane-associated guanylate kinase proteins have been known to interact various membrane receptors with their N-terminal segments designated the PDZ domains and to cluster these receptors at the target site of the cell membrane. NE-dlg/SAP102, a neuronal and endocrine tissue-specific MAGUK family protein, was found to be expressed in both dendrites and cell bodies in neuronal cells. Although NE-dlg/SAP102 localized at dendrites was shown to interact with N-methyl-D-aspartate receptor 2B via the PDZ domains to compose postsynaptic density, the binding proteins existing in the cell body of the neuron are still unknown. Here we report the isolation of a novel NE-dlg/SAP102-associated protein, p51-nedasin. Nedasin has a significant homology with amidohydrolase superfamily proteins and shows identical sequences to a recently identified protein that has guanine aminohydrolase activity. Nedasin has four alternative splice variants (S, V1, V2, and V3) that exhibited different C-terminal structures. NE-dlg/SAP102 is shown to interact with only the S form of nedasin which is predominantly expressed in brain. The expression of nedasin in neuronal cells increases in parallel with the progress of synaptogenesis and is mainly detected in cell bodies where it co-localizes with NE-dlg/SAP102. Furthermore, nedasin interferes with the association between NE-dlg/SAP102 and NMDA receptor 2B in vitro. These findings suggest that alternative splicing of nedasin may play a role in the formation and/or structural change in synapses during neuronal development by modifying clustering of neurotransmitter receptors at the synaptic sites.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Perioperative fractionated high-dose rate brachytherapy for malignant bone and soft tissue tumors.

PURPOSE: To investigate the viability of perioperative fractionated HDR brachytherapy for malignant bone and soft tissue tumors, analyzing the influence of surgical margin. METHODS AND MATERIALS: From July 1992 through May 1996, 16 lesions of 14 patients with malignant bone and soft tissue tumors (3 liposarcomas, 3 MFHs, 2 malignant schwannomas, 2 chordomas, 1 osteosarcoma, 1 leiomyosarcoma, 1 epithelioid sarcoma, and 1 synovial sarcoma) were treated at the Osaka University Hospital. The patients' ages ranged from 14 to 72 years (median: 39 years). Treatment sites were the pelvis in 6 lesions, the upper limbs in 5, the neck in 4, and a lower limb in 1. The resection margins were classified as intracapsular in 5 lesions, marginal in 5, and wide in 6. Postoperative fractionated HDR brachytherapy was started on the 4th-13th day after surgery (median: 6th day). The total dose was 40-50 Gy/7-10 fr/4-7 day (bid) at 5 or 10 mm from the source. Follow-up periods were between 19 and 46 months (median: 30 months). RESULTS: Local control rates were 75% at 1 year and 48% in 2 years, and ultimate local control was achieved in 8 (50%) of 16 lesions. Of the 8 uncontrolled lesions, 5 (63%) had intracapsular (macroscopically positive) resection margins, and all the 8 controlled lesions (100%) had marginal (microscopically positive) or wide (negative) margins. Of the total, 3 patients died of both tumor and metastasis, 3 of metastasis alone, 1 of tumor alone, and 7 showed no evidence of disease. Peripheral nerve palsy was seen in one case after this procedure, but no infection or delayed wound healing caused by tubing or irradiation has occurred. CONCLUSION: Perioperative fractionated HDR brachytherapy is safe, well tolerated, and applicable to marginal or wide surgical margin cases.

Adolescent↗
PubMed1999

Press perturbation in lattice ecosystems: parity law and optimum strategy

Press perturbation, in which the reproduction rate r of a target species is altered and held at higher or lower levels, is studied by computer simulation. We apply a lattice Lotka-Volterra model to idealized ecosystems, and obtain the optimum strategy roptdefined as follows: the steady-state density of the target species takes a maximum value at r=ropt. It is found that ropttakes a finite value, and it usually locates at a phase transition point. Moreover, we find that the long-term response to applied perturbation can be significantly predicted by parity law, where the parity is defined by whether the system contains an even or odd number of species. If the parity is even (odd), the density of the target species increases (decreases) with increasing r. An evolutionary meaning of roptis discussed in connection with the origin of sexual reproduction. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Interaction of NE-dlg/SAP102, a neuronal and endocrine tissue-specific membrane-associated guanylate kinase protein, with calmodulin and PSD-95/SAP90. A possible regulatory role in molecular clustering at synaptic sites.

NE-dlg/SAP102, a neuronal and endocrine tissue-specific membrane-associated guanylate kinase family protein, is known to bind to C-terminal ends of N-methyl-D-aspartate receptor 2B (NR2B) through its PDZ (PSD-95/Dlg/ZO-1) domains. NE-dlg/SAP102 and NR2B colocalize at synaptic sites in cultured rat hippocampal neurons, and their expressions increase in parallel with the onset of synaptogenesis. We have identified that NE-dlg/SAP102 interacts with calmodulin in a Ca2+-dependent manner. The binding site for calmodulin has been determined to lie at the putative basic alpha-helix region located around the src homology 3 (SH3) domain of NE-dlg/SAP102. Using a surface plasmon resonance measurement system, we detected specific binding of recombinant NE-dlg/SAP102 to the immobilized calmodulin with a Kd value of 44 nM. However, the binding of Ca2+/calmodulin to NE-dlg/SAP102 did not modulate the interaction between PDZ domains of NE-dlg/SAP102 and the C-terminal end of rat NR2B. We have also identified that the region near the calmodulin binding site of NE-dlg/SAP102 interacts with the GUK-like domain of PSD-95/SAP90 by two-hybrid screening. Pull down assay revealed that NE-dlg/SAP102 can interact with PSD-95/SAP90 in the presence of both Ca2+ and calmodulin. These findings suggest that the Ca2+/calmodulin modulates interaction of neuronal membrane-associated guanylate kinase proteins and regulates clustering of neurotransmitter receptors at central synapses.

Amino Acid Sequence↗
PubMed1999

Nonbacterial prostatitis caused by partial urethral obstruction in the rat.

The pathogenesis of nonbacterial prostatitis (NBP) is not understood mainly due to the lack of appropriate experimental models. We developed a new experimental model of NBP by inducing a partial obstruction of the urethra (PUO) in the rat. Male Wistar rats aged 12 weeks were used. PUO was produced by a nylon ligature on the urethra over a rubber tube. The tube was slipped out after the ligature had been tied. Two rats were examined histologically 6 h, 1 day, 3 days and 7 days after PUO. In another group, two rats were killed at 1, 3 and 7 days after the release of the PUO that had been left in place for 3 days. On day 3, another eight rats with PUO and eight control rats had 2 ml of urine in the bladder replaced by the same volume of lucifer yellow (LY; 10 microg/ml, MW 500), microperoxidase (MP; 20 microg/ml, MW 1900), horseradish peroxidase (HRP; 10 microg/ml, MW 40 000), or saline as control, respectively. Lymphocytic infiltration and interstitial edema were noted in the prostate following PUO, being most prominent on day 3. After the release of the PUO, these inflammatory changes gradually disappeared. Only LY was noted within the prostatic stroma of the rats 2 h after bladder instillation. Intraprostatic urinary reflux may be an etiologic factor in NBP. The present study showed that lower urinary tract obstruction caused NBP in the rat. Penetration of prostatic tissue by low-molecular-weight substances in the urine may trigger NBP.

Administration, Intravesical↗
PubMed1999

Anti-granulocyte antibody screening with extracted granulocyte antigens by a micro-mixed passive hemagglutination method.

BACKGROUND AND OBJECTIVES: Serologic tests for granulocyte antibodies, i.e., the granulocyte agglutination test and the granulocyte immunofluorescence test, require panels of typed granulocytes that cannot be preserved for more than a few hours. We have developed a new method in which granulocyte antigens, extracted into saline containing 3% sucrose, are coated onto U-type Terasaki plates. With this new method, we evaluated the micro-mixed passive hemagglutination test (EG-MPHA) for screening for granulocyte antibodies. MATERIALS AND METHODS: We tested the ability of the EG-MPHA to detect granulocyte antigens using 5 human antibodies specific for NA1, NA2, NB1, 5b, and Sar(a), and 8 different monoclonal antibodies for NA1, CD11a, CD11b, CD13, CD16, CD18 and HLA class I. Sera from 94 alloimmunized patients were screened by the chloroquine-treated EG-MPHA method. RESULTS: NA1, NA2, NB1, 5b, Sar(a), CD11a, CD11b, CD13, CD16, CD18 and HLA class I antigens were present in the extracted granulocyte antigen preparation. CD11b and HLA class I antigens were removed when the extracted granulocyte antigens were treated with chloroquine. Granulocyte antibody screening of sera from alloimmunized patients showed that approximately 30% of the anti-HLA-positive and 10% of the anti-HLA-negative sera were positive for granulocyte antibody by the chloroquine-treated EG-MPHA. The extracted granulocyte antigen panels could be stored frozen for at least 1 year at -80 degrees C. CONCLUSION: This new method is preferable for screening for granulocyte antibodies. In addition, it has the advantage of requiring only 5 microl of serum for each test.

Antibodies, Monoclonal↗
PubMed1999

A contractile activity that closes phagosomes in macrophages.

Studies of Fc-mediated phagocytosis by mouse macrophages identified a contractile activity at the distal margins of forming phagosomes. Time-lapse video microscopic analysis of macrophages containing rhodamine-labeled actin and fluorescein dextran showed that actin was concentrated at the distal margins of closing phagosomes. Phagocytosis-related contractile activities were observed when one IgG-opsonized erythrocyte was engaged by two macrophages. Both cells extended pseudopodia until they met midway around the erythrocyte. It was then constricted and pulled into two phagosomes, which remained interconnected by a string of erythrocyte membrane. Butanedione monoxime, an uncompetitive inhibitor of class II and perhaps other myosins, and wortmannin and LY294002, inhibitors of phosphoinositide 3-kinase, prevented the constrictions without inhibiting the initial pseudopod extension. Immunofluorescence microscopy showed the presence of myosins IC, II, V and IXb in phagosomes. Of these, only myosin IC was concentrated around the strings connecting shared erythrocytes, suggesting that myosin IC mediates the purse-string-like contraction that closes phagosomes. The sequential processes of pseudopod extension and contraction can explain how macropinosomes and spacious phagosomes form without guidance from a particle surface.

Actins↗
PubMed1999

Autoantibody against N(epsilon)-(carboxymethyl)lysine: an advanced glycation end product of the Maillard reaction.

Prolonged incubation of proteins with reducing sugar produces advanced glycation end products (AGEs), which are implicated as factors for aging and diabetic complications. We previously demonstrated the presence of N(epsilon)-(carboxymethyl)lysine (CML), one of the main AGE structures, in human and animal tissues using a monoclonal anti-CML antibody (6D12). These findings suggest that CML structures present in vivo could serve as immunogens to generate autoantibodies. This suggestion was tested in the present study. First, plasma samples from diabetic rats reacted positively with AGE bovine serum albumin (BSA). These reactivities increased with the duration of diabetic states and were inhibited specifically by CML-BSA. Second, a fraction purified from plasma of diabetic patients, which bound to AGE-BSA, showed a positive reaction to CML-BSA and furthermore also to human lens proteins, which are known to undergo CML modification in vivo. Finally, patients with renal failure caused by diabetes or nondiabetic pathologies had a higher autoantibody activity against CML structure than that in normal subjects or diabetic patients without renal failure. These results indicate that CML accumulated in vivo serves as an immunological epitope to generate an autoantibody specific for CML that might be used as a potential marker for diabetic nephropathy or chronic renal failure.

Animals↗
PubMed1999

Intraoperative extracorporeal autogenous irradiated bone grafts in tumor surgery.

There are several procedures for reconstruction of bony defects after resection of malignant musculoskeletal tumors. The clinical results of intraoperative extracorporeal autogenous irradiated bone grafts in 20 patients with musculoskeletal tumors are discussed. The authors' method of treatment consists of: (1) wide en bloc resection of the tumor with involved bone; (2) curettage of the tumor from the resected bone; (3) extracorporeal irradiation with 50 Gy as a bolus single dose to the isolated bone; and (4) reimplantation of the irradiated bone into the host with fixation devices. Twelve bone sarcomas and eight soft tissue sarcomas with bone involvement were treated surgically with this reconstruction method after wide resection of the tumors. The irradiated bone was used as an intercalary graft in seven cases, as an osteoarticular graft in 11 cases, and as a hemicortical graft in two cases. The theoretical advantages of this method are certain sterilization of tumor cells with radiation, easy availability and good adaptation of size and shape, no risk of disease transmission, preservation of bone stock and ligamentous tissue, and no immunologic reaction. Radiologically, bony union occurred in 23 of 29 (79%) osteotomy sites. The overall radiographic evaluation rating was 74% and the functional rating was 73% according to the International Society of Limb Salvage rating system. Nonunion (20%) and infection (15%) were the two major complications. Preservation of the tendon insertions and ligamentous structures of the irradiated bone seemed to restore excellent joint function. No local recurrence was detected from the irradiated bones during the mean followup of 45 months. These results indicate intraoperative extracorporeal irradiated bone graft can be a widely applicable method for reconstruction in tumor surgery.

Adolescent↗
PubMed1998

Reward-quality dependent anticipation in rat nucleus accumbens.

Single unit recording in rat nucleus accumbens (NAcc) was used to ascertain NAcc neuronal activity in mediating of reward including its anticipation. Of the 103 neurons investigated, 63% showed some response in connection with the task activity. Of these, 20 units responded during delivery of the primary reward (food and/or water) and five responded during the time period preceding reward if the reward was delayed (four to food, one to water). These result suggest that NAcc neurons responded not only to the delivery of primary reward and task inducing anticipation of reward, but also represent the difference of reward quality between food and water specifically.

Animals↗
PubMed1998

Impairment of cell adhesion by expression of the mutant neurofibromatosis type 2 (NF2) genes which lack exons in the ERM-homology domain.

Neurofibromatosis 2 (NF2) is an inherited disorder characterized by a predisposition to multiple intracranial tumors. The protein encoded by the NF2 gene has striking similarities to ezrin, radixin and moesin (ERM) proteins which link membrane proteins to the cytoskeleton. Therefore, it can be speculated that the disruption of cytoskeletal organization by alterations in the NF2 gene is involved in the development of tumors. It has been reported that the majority of NF2 mutations were nonsense or frameshift mutations that result in premature termination of translation. To facilitate the detection of these mutations, we performed protein truncation test and found that 11 of 14 NF2 patients had truncational mutations (79%). Seven of the 11 patients (64%) had a splicing abnormality which lead to absence of exons in the ERM homology domain. To examine the biological significance of the exon-missing mutations in the ERM homology domain, we expressed the wild-type (wt-NF2) and the various mutant NF2s (mu-NF2s) in a fibroblast cell line by using both liposome-mediated transfection and nuclear microinjection of the expression plasmids. The wt-NF2 showed intense punctate staining in the perinuclear cytoplasm in addition to overall staining of the submembranous area, whereas the mu-NF2s lacking exons in the ERM homology domain showed granular staining at the perinuclear region without any accumulation at the submembrane region. Microinjection of wt-NF2 cDNA into the nucleus of VA13 cells revealed that wt-NF2 protein induced a progressive elongation of cell processes. Furthermore, cells that expressed mu-NF2 had decreased adhesion, which resulted in detachment from the substratum. These findings suggested that the exon-missing mutations in the ERM-homology domain may affect cell membrane-cytoskeleton signaling and consequently disrupt cell-to-cell or cell-to-matrix interaction.

Adolescent↗
PubMed1998

Splicing patterns of type XI collagen transcripts act as molecular markers for osteochondrogenic tumors.

Primary transcripts for three distinct alpha chains of the type XI collagen molecule (alpha1(XI), alpha2(XI) and alpha3[XI]) undergo tissue-specific alternative splicing during the process of osteochondrogenesis. In the present study, we analyzed the splicing patterns of type XI collagen genes in osteochondrogenic tumors as well as in various normal tissues using the reverse transcription-polymerase chain reaction method. Analysis of normal subjects revealed the coordinated expression of short alpha1(XI), alpha2(XI) and alpha3(XI) transcripts in the normal differentiated cartilage. Osteochondroma followed this pattern, reflecting the highly chondrogenic phenotype of this benign tumor. Another benign tumor, chondroblastoma, exclusively expressed the long alpha1(XI) transcript, probably reflecting the lack of a chondrogenic nature. Among malignant chondrogenic tumors, the splicing patterns of type XI collagen transcripts were more complex, showing dissociated expression of long alpha1(XI) and short alpha2(XI) mRNAs. This expression pattern may reflect heterogeneous cell populations and may also reflect various levels of cell differentiation in malignant tumors. In addition, short alpha3(XI) expression switched to the long transcript as chondrosarcomas became more aggressive. Thus, the alternative splicing of type XI collagen genes seems to be oncodevelopmentally regulated and splicing analysis may therefore be a useful marker for chondrogenic tumors.

Alternative Splicing↗
PubMed1998

Florid periosteal reaction and focal fibrocartilaginous dysplasia.

Focal fibrocartilaginous dysplasia (FFCD) is a rare condition causing tibia vara in childhood. It is characterized by progressive tibia vara in young children with a characteristic radiographic lesion. This paper is thought to be the first to describe FFCD exhibiting florid periosteal reaction at the time of presentation with a subtle faint osteolytic lesion in the diametaphysis of the proximal tibia.

Bone Diseases, Developmental↗
PubMed1998

Treatment of chronic osteomyelitis using calcium hydroxyapatite ceramic implants impregnated with antibiotic.

We treated eighteen patients with chronic osteomyelitis by implanting pieces of antibiotic-impregnated calcium hydroxyapatite ceramic into a cavity produced after thorough surgical excision of necrotic tissue. Within three months the infected sites had all healed. During follow-up ranging from 24 to 75 months there was no recurrence of infection. Two of the patients had infected prosthetic joints which were successfully revised. Infection was controlled and incorporation of the ceramic material into host bone was demonstrated radiographically. We recommend the use of porous pieces of calcium hydroxyapatite impregnated with antibiotic as a new system for drug delivery in the treatment of chronic osteomyelitis.

Adolescent↗
PubMed1998

Alveolar soft part sarcoma.

We report a case of alveolar soft part sarcoma (ASPS) of the thigh with lung metastases in a 22-year-old woman. The findings of digital subtraction angiography (DSA) and MRI contributed to the diagnosis of ASPS. Especially dynamic contrast-enhanced MRI was useful for evaluating the effect of chemoembolotherapy.

Adult↗