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Biomedical subjects

M Takahashi

Publications and source records attributed to M Takahashi.

At least 37 records · Page 2Linked to original sources

Comprehensive management of chemical substances in a water environment using PRTR data.

The annual quantity of discharge of 354 chemical substances from each business has been released based on PRTR law in Japan since 2003. MLIT and municipalities should be responsible for managing chemical risk in public water bodies through communication with stakeholders, such as the public and businesses. However, it is economically difficult to measure the discharge loads and behaviour of all chemical substances and reveal which substances should be particularly managed in each basin. NILIM has begun studies on survey methods to understand the discharge and behaviour of chemical substances in each basin based on PRTR information, and to conduct risk management of chemical substances in cooperation with stakeholders such as the public and businesses. We selected 30 chemical substances, such as those listed or nominated in environmental criteria and endocrine disrupters, collected the volume of discharge of chemical substances from public and industrial wastewater treatment plants using PRTR information, and surveyed their behaviour in the river in the model area. As a result, the discharge of 12 chemical substances were reported in PRTR, and 17 substances were detected in the river. Some inorganic compounds were detected intensively near discharge sites reported in the PRTR. But some organic compounds and endocrine disrupters, such as oestrone, were detected although their discharge was not reported in the model area in the PRTR. It suggested that PRTR information is useful to identify hot spots, but further study is needed to understand the discharge of chemical substances from small businesses, farmland and houses.

Environmental Monitoring↗

[Mid-term results of overlapping cardiac volume reduction for ischemic cardiomyopathy].

BACKGROUND: Left ventricular restoration (LVR) is thought to be effective for ischemic cardiomyopathy (ICM). We assessed the early and mid-term results of overlapping cardiac volume reduction (OLCVR) as an operation for LVR on patients with ICM. METHODS: From February to June 2004, 4 patients with ICM underwent OLCVR in our department. RESULTS: There was no death. Significant decreases in the left ventricular end diastolic volume index and in the left ventricular end systolic volume index were observed in the early postoperative period in all the 4 patients. These effects were still evident 1 year later, with improved New York Heart Association (NYHA) functional class and a smaller left ventricular diastolic diameter. One patient required implantation of a cardioverter defibrillator 16 months postoperatively. CONCLUSION: The favorable early and mid-term results of the OLCVR indicate that it is an effective procedure for patients with ICM.

Aged↗

Carbohydrate-binding specificities of mouse ficolin A, a splicing variant of ficolin A and ficolin B and their complex formation with MASP-2 and sMAP.

Ficolins are a group of proteins mainly consisting of collagen-like and fibrinogen-like domains and are thought to play a role in innate immunity via their carbohydrate-binding activities. Two types of ficolins have been identified in mice, ficolin A, and ficolin B. However, their structure and function are not fully understood. In this study, we isolated the cDNA encoding a novel variant of ficolin A having a shorter collagen-like domain and a longer gap sequence, which was generated from the ficolin A gene by alternative splicing. We delineated the structure and function of mouse ficolins, including this splicing variant, by preparing the respective recombinants. Recombinant ficolin A, its splicing variant, and ficolin B showed multimeric structures and revealed binding to both N-acetylglucosamine and N-acetylgalactosamine. Interestingly, ficolin B specifically recognized sialic acid residues. Ficolin A and its variant, but not ficolin B, bound to mannose-binding lectin (MBL)-associated serine protease-2 (Masp-2) and small MBL-associated protein (smap), and the resulting complexes showed a potent complement activating capacity. In addition, smap competed with Masp-2 in association with ficolin A and its variant, and inhibited the complement activation by the ficolin A (or ficolin A variant)/MASP-2 complex, indicating its regulatory role in the lectin pathway. These results suggest that ficolin A and its variant function as recognition molecules of the lectin pathway, and ficolin B plays a distinct role through its unique carbohydrate-binding specificity.

Adaptor Proteins, Signal Transducing↗

Campylobacter gene polymorphism as a determinant of clinical features of Guillain-Barré syndrome.

BACKGROUND: Ganglioside epitopes on Campylobacter jejuni are hypothesized as the key to the development and characterization of Guillain-Barré syndrome (GBS), but a comprehensive theory has yet to be established. A C jejuni gene, cst-II, involved in the biosynthesis of ganglioside-like lipo-oligosaccharide, shows a polymorphism (Asn/Thr51) that affects ganglioside epitopes. OBJECTIVE: To examine the hypothesis that this polymorphism determines autoantibody reactivity, and thereby neurologic presentations in GBS. METHODS: C jejuni isolates were collected from 105 GBS (including its variants) and 65 uncomplicated enteritis patients. The authors examined the frequency of cst-II and polymorphism (Asn/Thr51) in connection with the bacterial ganglioside epitopes, autoantibody reactivities against GM1, GD1a, and GQ1b, and patients' neurologic findings. RESULTS: Neuropathic strains more frequently had cst-II, in particular cst-II (Thr51), than did enteritic ones (85% vs 52%; p < 0.001). Strains with cst-II (Asn51) regularly expressed the GQ1b epitope (83%), whereas those with cst-II (Thr51) had the GM1 (92%) and GD1a (91%) epitopes. The presence of these bacterial epitopes in neuropathy patients corresponded to autoantibody reactivity. Patients infected with C jejuni (Asn51) more often were positive for anti-GQ1b IgG (56% vs 8%; p < 0.001) and had ophthalmoparesis (64% vs 13%; p < 0.001) and ataxia (42% vs 11%; p = 0.001). Patients who had C jejuni (Thr51) more frequently were positive for anti-GM1 (88% vs 35%; p < 0.001) and anti-GD1a IgG (52% vs 24%; p = 0.006) and had limb weakness (98% vs 71%; p < 0.001). CONCLUSIONS: The genetic polymorphism of C jejuni determines autoantibody reactivity as well as the clinical presentation of Guillain-Barré syndrome (GBS), possibly through modification of the host-mimicking molecule. The GBS paradigm is the first to explain the detailed pathogenesis of a postinfectious, autoimmune-mediated, molecular mimicry-triggering disorder.

Autoantibodies↗

Intraoperative cortical mapping has low sensitivity for the detection of motor function in proximity to a tumor in the primary motor area.

Six patients with brain tumors within or near the primary motor cortex underwent preoperative functional magnetic resonance imaging (fMRI) and intraoperative cortical mapping, and the accuracy of those techniques for localization of the primary motor cortex and motor function beside the tumor were determined by comparison against neuroanatomical correlates from pre-, intra- and postoperative neurological observations. The location of the primary motor cortex was detected by intraoperative cortical mapping in 5 of 6 cases and by fMRI in all 6 cases. Brain mapping provided equivocal information on the cortical representation of motor territories, and with the technique used in close proximity to the tumor, the motor territories were not detected in all but 1 case. In contrast, the areas controlling motor function in close proximity to the tumor were detected by fMRI in 4 of 6 cases. These data indicate that intraoperative cortical mapping has a low sensitivity for the detection of motor function in the area beside the tumor. Therefore, this technique may not be sufficient to prevent compromise of motor areas during tumor resection.

Aged↗

High prevalence of hepatitis B, C and delta virus infections among blood donors in Mongolia.

Serum samples obtained from 289 first-time and 114 repeat donors at the Blood Center of Mongolia (MBC) were tested for serological and molecular markers of hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) infections. Among the 403 blood donors, 33 (8.2%), 21 (5.2%), and 27 (6.7%) tested positive for hepatitis B surface antigen (HBsAg) and/or HBV DNA, HCV RNA, and HDV RNA, respectively. Collectively, 55 donors were viremic for one or more of these viruses, and included 54 first-time donors (18.7%) and 1 repeat donor (0.9%) (P < 0.0001). One discrepant case with HBsAg detectable only at MBC was negative for HBsAg, HBV DNA and anti-HBc in this study. Four donors who were HCV-viremic in this study were negative for anti-HCV by the MBC method. Further efforts to increase the sensitivity and specificity of the currently-used tests are urgently required in Mongolia. Three donors who were positive for anti-HBc and anti-HDV but negative for HBsAg, had both HBV DNA and HDV RNA. This suggests that introduction of a new anti-HDV serological test is useful for not only HDV screening but also HBV screening of anti-HBc-positive, HBsAg negative donors, considering a possibility of viral interference by coexisting HDV.

Adolescent↗

Phenylalanine ammonia-lyase modified with polyethylene glycol: potential therapeutic agent for phenylketonuria.

Phenylketonuria (PKU) is an autosomal recessive genetic disease caused by the defects in the phenylalanine hydroxylase (PAH) gene. Individuals homozygous for defective PAH alleles show elevated levels of systemic phenylalanine and should be under strict dietary control to reduce the risk of neuronal damage associated with high levels of plasma phenylalanine. Researchers predict that plant phenylalanine ammonia-lyase (PAL), which converts phenylalanine to nontoxic t-cinnamic acid, will be an effective therapeutic enzyme for the treatment of PKU. The problems of this potential enzyme therapy have been the low stability in the circulation and the antigenicity of the plant enzyme. Recombinant PAL originated from parsley (Petroselinum crispum) chemically conjugated with activated PEG2 [2,4-bis(O-methoxypolyethyleneglycol)-6-chloro-s-triazine] showed greatly enhanced stability in the circulation and was effective in reducing the plasma concentration of phenylalanine in the circulation of mice. PEG-PAL conjugate will be an effective therapeutic enzyme for the treatment of PKU.

Animals↗

Observation of a molecular frame (e, 2e) cross section: an (e, 2e + M) triple coincidence study on H(2).

We report the first experimental results showing transition-specific anisotropy of molecular frame (e, 2e) cross sections. Vector correlations between the two outgoing electrons and the fragment ion have been measured for specific ionization-excitation processes of H2. The results enable us to obtain molecular frame (e, 2e) cross sections for transitions to the 2ssigma(g) and 2psigma(u) excited states of H(2)(+), thereby making stereodynamics of the electron-molecule collisions directly visible.

Journal Article↗

Antecedent infections in Fisher syndrome: a common pathogenesis of molecular mimicry.

OBJECTIVE: To assess the production mechanism of anti-GQ1b autoantibody in Fisher syndrome (FS). METHODS: The authors conducted a prospective case-control serologic study of five antecedent infections (Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, and Haemophilus influenzae) in 73 patients with FS and 73 sex- and age-matched hospital controls (HCs). Serologic evidence in FS patients of C. jejuni (21%) and H. influenzae (8%) infections was present significantly more often than in the HCs. None of the five pathogens examined was found in the 49 (67%) patients with FS. Anti-GQ1b IgG antibody was detected in most FS patients infected with C. jejuni or H. influenzae. Mass spectrometry analysis identified a C. jejuni strain (CF93-6) carrying a GT1a-like lipo-oligosaccharide (LOS) that had been isolated from an FS patient. Immunization of complex ganglioside-lacking knockout mice with the GT1a-like LOS generated IgG class monoclonal antibodies (mAbs) that reacted with GQ1b and GT1a. Thin-layer chromatography with immunostaining showed that anti-GQ1b mAb bound to the C. jejuni LOS (50% of the 20 FS-related strains) more commonly than in the Guillain-Barré syndrome (GBS)-related (7% of 70) or enteritis-related (20% of 65) strains. Anti-GM1 and anti-GD1a mAbs also reacted with the LOS from some FS-related strains (both 20%), but binding frequencies were higher in the GBS-related strains (74 and 57%). The GQ1b epitope was detected in 4 (40%) of the 10 FS-related H. influenzae strains but was absent in strains from patients with GBS (n = 4) and uncomplicated respiratory infections (n = 10). CONCLUSIONS: C. jejuni and H. influenzae are related to Fisher syndrome (FS) development, and production of anti-GQ1b autoantibody is mediated by the GQ1b-mimicking lipo-oligosaccharides on those bacteria. The causative agents remain unclear in the majority of patients with FS.

Adult↗

Comparison of susceptibility to SIVmac239 infection between CD4(+) and CD4(+)8(+) T cells.

CD4-bearing T cells are the primary targets for human immunodeficiency virus type 1(HIV-1)/simian immunodeficiency virus (SIV) infection. However, it is unclear whether the susceptibility of CD4-bearing T cells including CD4 single positive and CD4/8 double positive T cells to HIV/SIV infection is the same or not. In this study, we compared the susceptibility to SIV infection between CD4(+) and CD4(+)8(+) T cells, using Herpesvirus saimiri (HVS)-transformed CD4(+) and CD4(+)8(+) T cells established from peripheral blood mononuclear cells (PBMC) of rhesus macaques. Although there was little difference between the two CD4-bearing T cell population in the expression level of CD4 molecules and chemokine receptors such as CXCR4 and CCR5, SIV replicated more efficiently in CD4(+)8(+) T cells than in CD4(+) T cells. Moreover, we found that reverse transcription initiated more efficiently in CD4(+)8(+) T cells than in CD4(+) T cells and that the cell lysates from CD4(+) T cells impaired the RT activity more strongly than that from CD4(+)8(+) T cells. These findings suggest that intracellular environment in CD4(+) 8(+) T cells is better for reverse transcription and that the infection of those CD4(+)8(+) T cells might play critical and different roles in HIV-1/SIV infection and dissemination.

Animals↗

Preoperative fMRI, tractography and continuous task during awake surgery for maintenance of motor function following surgical resection of metastatic tumor spread to the primary motor area.

The goal of the present study was to determine the efficacy of preoperative fMRI, tractography, and intraoperative continuous task during awake surgery in preserving postoperative motor function in patients undergoing resection of metastatic brain tumors in or near the primary motor area. Three patients with metastatic brain tumors in the primary motor area elected to undergo surgical treatment. Preoperative fMRI and tractography were performed, and various primary motor areas (e. g., hand, arm, face and leg) were identified and confirmed by cortical mapping or by the outcome of awake surgery. Cortical mapping and continuous appropriate task were performed during awake surgery. Preoperative fMRI and tractography correctly identified the primary motor area. In contrast, cortical mapping identified the gyrus of the primary motor area but was unable to identify specific primary motor areas, such as those for the hand or arm, which were compressed by the tumor. Tumor resection was terminated when any deterioration in continuous task performance was observed during awake surgery. Paresis was transient and resolved within one week in all cases. The combination of preoperative fMRI, tractography and continuous task during awake surgery helped to maintain motor function following surgical management of metastatic brain tumors of the primary motor cortex.

Brain Mapping↗

Rapid onset of quetiapine-induced diabetic ketoacidosis in an elderly patient: a case report.

New onset diabetes mellitus (DM) and diabetic ketoacidosis (DKA) among patients using atypical antipsychotics is of clinical importance [1,2,5,7-10]. Recently, atypical antipsychotics have been more widely used in the treatment of behavioral and psychological symptoms with dementia (BPSD) than conventional neuroleptics because of a reduced tendency for movement disorders and psychomotor retardation. We report a case of reversible DKA and new-onset DM that developed in a demented patient who was treated with quetiapine for 14 days.

Aged↗

Association of motor deficits with head position during awake surgery for resection of medial motor area brain tumors.

OBJECTIVE: Resection of tumors involving the motor area frequently results in postoperative motor deficits. In an attempt to prevent poor motor outcomes, our institution has utilized preoperative fMRI and tractography as well as intraoperative cortical mapping and continuous motor tasks during awake surgery in patients with motor area tumors. In one case, a patient demonstrated deterioration in continuous motor task performance before initiation of tumor resection. Thus, the goal of this study was to evaluate the relationship between head position and development of intraoperative or postoperative motor deficits in five patients with motor area tumors. CLINICAL PRESENTATION: In four cases, the patient's head was rotated 60 degrees from the supine position. In two cases, in which the tumor was located relatively medially, deterioration in continuous motor task function was noted prior to resection of the tumor. In the two other cases, in which the tumor was located relatively laterally, there was no deterioration of continuous motor task performance until resection of the tumor. Another patient, in whom the tumor was located relatively medially, underwent surgery with the head positioned straight and with the patient in a half-sitting position. This patient did not experience deterioration of continuous motor task performance during the surgery. CONCLUSION: These data suggest that head positioning can have a significant impact on motor function in patients with motor area tumors. Furthermore, the straight head position may be the preferred positioning, particularly for patients with tumors located on the medial side of motor area.

Aged↗

Effect of prostaglandin E2, lipopolysaccharide, IFN-gamma and cytokines on the generation and function of fast-DC.

BACKGROUND: Recent reports have described a new strategy for differentiation and maturation of monocyte-derived DC within only 48 h of in vitro culture (fast-DC). We compared the ability of various maturation stimuli with the generation of Ag-specific T-cell responses and generation of functional fast-DC. METHODS: CD14+ cells were treated with GM-CSF and IL-4 for 1 day to generate immature DC, and were then matured with either inflammatory cytokines or a combination of lipopolysaccharide (LPS) and INF-gamma. Mature DC were then used to study the effect of prostaglandin E2 (PGE2) on the stimulatory function of fast-DC. RESULTS: fast-DC were CD14- and expressed mature DC surface markers, and maintained this phenotype after withdrawing the cytokine from culture. Treatment of fast-DC with a combination of LPS and INF-gamma promoted the maturation of highly uniform fast-DC. The T-cell proliferative response to DC was enhanced by inclusion of PGE2 in the MCM-mimic (TNF-a, IL-1 a, IL-6, PGE2) cocktail. DISCUSSION: fast-DC are very effective; they not only reduce the labor, cost and time required for in vitro DC development, but may also represent a model more closely resembling DC differentiation from monocytes in vivo.

Antineoplastic Agents↗

Bone marrow cells differentiate into wound myofibroblasts and accelerate the healing of wounds with exposed bones when combined with an occlusive dressing.

BACKGROUND: The usefulness of bone marrow cells in accelerating wound healing has not been evaluated despite increasing evidence that bone marrow contains mesenchymal stem cells that have multipotentiality to differentiate into various types of cells after they enter the microenvironment of a specific tissue (niche). OBJECTIVES: To determine the effects of bone marrow cells and occlusive dressings in promoting wound healing in rats. METHODS: We investigated by grafting, biopsy and immunohistochemistry whether various types of cells derived from green fluorescent protein (GFP)-transgenic rats would differentiate into wound component cells when administered topically on the wounds of rats. We also investigated whether topical application of bone marrow cells with an occlusive dressing would accelerate the healing of wounds with exposed bones, as measured by planimetry. RESULTS: GFP-labelled bone marrow cells contained multipotent stem cells that sufficiently differentiated into wound myofibroblasts presenting with alpha-smooth muscle actin in granulation tissue. Other types of cells, including myocytes, adipocytes, peripheral blood cells from buffy coat and dermal fibroblasts, did not express myofibroblast characteristics morphologically or immunohistochemically. Application of bone marrow cells and an occlusive dressing accelerated the repair of wounds with exposed bones, compared with an occlusive dressing only or with the topical administration of bone marrow cells plus a semidry to dry dressing. CONCLUSIONS: Our study indicates that bone marrow cells accelerate the healing of wounds at least in part through their differentiation into wound myofibroblasts. Thus, treatment of wounds with bone marrow cells and a supportive occlusive dressing is effective in promoting the formation of healthy granulation tissue and also for the preparation of an ideal wound bed.

Animals↗

Large haematoxylin-stainable keratohyaline granules in solar keratoses: immunohistochemical comparison using anti-Ted-H-1 antibody and antiloricrin antibody.

BACKGROUND: Our previous study showed that large keratohyaline granules (KHG) in molluscum contagiosum that stained with haematoxylin also reacted with anti-Ted-H-1 monoclonal antibody (mAb), but not with antifilaggrin mAb or antiloricrin polyclonal antibody (pAb). This finding indicated that the Ted-H-1 antigenic protein is a haematoxylin-stainable protein in KHG. OBJECTIVES: To clarify the identity of the major component protein of the large KHG in solar keratosis, another disorder in which large KHG are observed. METHODS: An enzyme immunohistochemical study was performed using antifilaggrin mAb, anti-Ted-H-1 mAb and antiloricrin pAb. Immunofluorescent double staining and immunoelectron microscopic analyses were performed using anti-Ted-H-1 mAb and antiloricrin pAb. RESULTS: Antifilaggrin mAb, anti-Ted-H-1 mAb and antiloricrin pAb reacted with normal KHG in nonlesional skin of solar keratosis, while only anti-Ted-H-1 mAb reacted with the large KHG in the lesions of solar keratosis. Antifilaggrin mAb did not react with large KHG. Antiloricrin pAb reacted with the cell membrane of the stratum granulosum, but not with large KHG. CONCLUSIONS: These findings suggest that the haematoxylin-stainable protein in the large KHG would be a Ted-H-1 antigen protein which was neither filaggrin nor loricrin.

Aged↗

Partial deletions of the W chromosome due to reciprocal translocation in the silkworm Bombyx mori.

In the silkworm, Bombyx mori (female, ZW; male, ZZ), femaleness is determined by the presence of a single W chromosome, irrespective of the number of autosomes or Z chromosomes. The W chromosome is devoid of functional genes, except the putative female-determining gene (Fem). However, there are strains in which chromosomal fragments containing autosomal markers have been translocated on to W. In this study, we analysed the W chromosomal regions of the Zebra-W strain (T(W;3)Ze chromosome) and the Black-egg-W strain (T(W;10)+(w-2) chromosome) at the molecular level. Initially, we undertook a project to identify W-specific RAPD markers, in addition to the three already established W-specific RAPD markers (W-Kabuki, W-Samurai and W-Kamikaze). Following the screening of 3648 arbitrary 10-mer primers, we obtained nine W-specific RAPD marker sequences (W-Bonsai, W-Mikan, W-Musashi, W-Rikishi, W-Sakura, W-Sasuke, W-Yukemuri-L, W-Yukemuri-S and BMC1-Kabuki), almost all of which contained the border regions of retrotransposons, namely portions of nested retrotransposons. We confirmed the presence of eleven out of twelve W-specific RAPD markers in the normal W chromosomes of twenty-five silkworm strains maintained in Japan. These results indicate that the W chromosomes of the strains in Japan are almost identical in type. The Zebra-W strain (T(W;3)Ze chromosome) lacked the W-Samurai and W-Mikan RAPD markers and the Black-egg-W strain (T(W;10)+(w-2) chromosome) lacked the W-Mikan RAPD marker. These results strongly indicate that the regions containing the W-Samurai and W-Mikan RAPD markers or the W-Mikan RAPD marker were deleted in the T(W;3)Ze and T(W;10)+(w-2) chromosomes, respectively, due to reciprocal translocation between the W chromosome and the autosome. This deletion apparently does not affect the expression of Fem; therefore, this deleted region of the W chromosome does not contain the putative Fem gene.

Animals↗

Analysis of evolutionary conservation in CD1d molecules among primates.

The hereditary conservation in the genetically encoded CD1D sequences of various primates was analyzed. Genomic CD1D sequences of 17 rhesus macaques with distinct origins, eight Indian and nine Chinese, were examined and differences of only one or two nucleotides were detected and the consensus sequence of rhesus CD1D was determined. CD1D consensus sequences of three African green monkeys (AGMs) and the rhesus monkeys were then compared to study the evolutionary differences among interspecies. The CD1D consensus sequence determined from AGMs apparently differed by seven nucleotides from the rhesus consensus sequence, and nucleotide difference induced only three amino acid changes within Exon3, corresponding to the alpha2 domain of CD1d having a hydrophobic ligand-binding pocket. Such changes in the alpha2 domain may alter the characteristics of the SIV-derived glycolipid/lipid antigens presented by each CD1d molecule to innate natural killer T cells. In addition, the CD1D genomic sequences of three chimpanzees (chimps) were determined. To our surprise, although Exon2 and Exon3 reflecting antigen-binding alpha1 and alpha2 domains in chimps' CD1D were identical to that in humans except one amino acid, three amino acids within Exon4, reflecting alpha3 domain, were distinct from humans, and one of them was identical to those in rhesus and AGM CD1D. On the basis of the findings, the evolutionary relationship of the CD1d molecules among the various primates and their HIV-1/SIV susceptibility will be discussed.

Amino Acid Sequence↗