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Biomedical subjects

Daisuke Nakajima

Publications and source records attributed to Daisuke Nakajima.

At least 19 recordsLinked to original sources

Donor selection in living-donor lung transplantation for familial pulmonary fibrosis: A narrative review and single-center practical approach.

In Japan, living-donor lobar lung transplantation (LDLLT) remains an important therapeutic option because of the persistent shortage of brain-dead donors. Interstitial lung diseases (ILDs) are a major indication for transplantation; however, the use of biologically related donors raises concerns regarding shared genetic susceptibility. Approximately 20% of ILD patients have a family history of ILD, referred to as familial pulmonary fibrosis (FPF). FPF is defined as fibrotic ILD occurring in at least two first- or second-degree relatives and is associated with poor prognosis regardless of the presence of identifiable genetic variants. Furthermore, interstitial lung abnormalities have been reported in 14-22% of first-degree relatives of patients with FPF, suggesting a substantial latent risk of disease development both in donors and recipients. These findings have important implications for donor selection in LDLLT. At Kyoto University Hospital, first-degree relatives from affected lineages are generally excluded as donor candidates, whereas relatives from unaffected family branches may be considered after careful individual assessment. Even in cases without a family history, biologically related donor candidates should be adequately informed of the potential future risk of ILD. Future directions include the incorporation of genetic testing and telomere length assessment and the establishment of prospective cohorts to enable risk stratification and long-term outcome evaluation. In conclusion, the selection of donors for LDLLT in patients with FPF requires a cautious and individualized approach that integrates family history, clinical evaluation, and genetic information to balance donor safety with access to transplantation.

Humans↗

Activity related to the carcinogenicity of plastic additives in the benzophenone group.

This study examines the activities relating to the carcinogenicity of six types of benzophenone derivatives (benzophenone, 2-hydroxy-4-octyloxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone and 2,2'-dihydroxy-4,4'-dimethoxybenzophenone) currently used in plastic products as additives to serve as ultraviolet absorbing agents. The evaluation of the initiation activity used a light absorption umu-test, a luminescent umu-test and the Ames test. The promotion activity was examined by a Bhas assay, a method that uses Bhas 42 cells for the formation of transformation foci. The luminescent umu-test indicated positive initiation activity of 2-hydroxy-4-methoxybenzophenone, and pseudo-positive activity of 2,4-dihydroxybenzophenone and 2,2'-dihydroxy-4-methoxybenzophenone. In the Ames test, 2-hydroxy-4-octyloxybenzophenone showed pseudo-positive initiation activity. Conversely, 2,4-dihydroxybenzophenone indicated weak promotion activity at 10 microg/ml concentration.

Benzophenones↗

Measurements of exposure concentrations of benzene, toluene and xylene, and amounts of respiratory uptake.

With respect to benzene, toluene, and o-, m- and p-xylene contained in indoor air, this study determined the amounts of their uptake through the human respiratory system using the difference between concentrations in inhalation and exhalation, and examined their relationship to concentrations in blood and urine measured before and after exposure. At relatively high concentrations, respiratory absorption of these compounds tended to increase rapidly in the early stage of exposure but decrease after several hours. It was also confirmed that concentrations of these compounds in both blood and urine increased during the first 3 hours of exposure. These results suggested that measurements of concentrations in inhalation and exhalation may provide a simple method for estimating the extent of respiratory exposure to these substances.

Absorption↗

Measurement of volatile organic compounds (VOCs) in new residential buildings and VOCs behavior over time.

For the purpose of the investigation of characteristics of VOCs found indoors in recently constructed residential buildings, we measured the behavior of VOCs which were sampled at one-month intervals over a period of one year from the, initial occupancy date in both a detached house and an apartment in a multiple' dwelling. At the first passive sampling from the wooden detached residential building, n-hexane, n-undecane, toluene, ethylacetate, methylethylketone, alpha-pinene and (+)-limonene were present in relatively high concentrations of 10 ppb or higher in the living room. Then these VOCs showed a declining trend with time. p-Dichlorobenzene showed an extremely high concentration (approx. 320 ppb) in June, which subsequently declined with each passing month. There is a high possibility that the cause was the use of a pesticide containing p-dichlorobenzene during the period of changeover from winter to summer clothes in June. On the other hand, from the multiple dwelling, four VOCs showed values of 10 ppb or more (toluene, 1,2,4-trimethylbenzene, methylethylketone and alpha-pinene). Of these VOCs, methylethylketone concentration was in excess of 100 ppb, and then also showed a declining trend with time. Even for new residential buildings completed during the same time frame, it was shown that the types of VOC contaminants and their concentrations varied significantly.

Air↗

Determination of toluene in brain of freely moving mice using solid-phase microextraction technique.

For the purpose of measuring the pharmacokinetics of inhaled toluene in the brain of mice, we developed a method for the direct detection of toluene by gas chromatography/mass spectrometry (GC/MS). The method uses a solid-phase microextraction (SPME) fiber inserted into the mouse' hippocampus (CA1) through a cannula fixed onto the animal. BALB/c mice were exposed to 0, 0.9, 9, 50 and 90 ppm toluene for 30 min. The toluene level detected near the hippocampus by this method after exposure to 0.9 ppm toluene in air showed no significant difference from the level found in the non-exposure control group; however, the toluene level increased significantly after exposure to concentrations of 9, 50 and 90 ppm. These increases were concentration-dependent. In addition, the pharmacokinetics of toluene in the brain of mice exposed to 50 ppm toluene showed that the toluene level decreased rapidly after the exposure, and returned to control levels after 60 min. This study describes the method which has successfully detected toluene levels in the brain of conscious, free-moving mice for the first time.

Animals↗

[Neurological complications during and after the treatment of acute lymphocytic leukemia].

To explore the frequency and prognosis of neurological complications of acute lymphocytic leukemia, retrospective studies were made of patients with acute lymphocytic leukemia. Neurological complications were found in 13 of 100 patients during and after treatment. They were caused by chemotherapy in 8 patients, irradiation therapy in 2, vitamin B1 deficiency in 1, and unknown in 2. Medications primarily relevant to these complications were methotrexate in 5 patients, L-asparaginase in 2, cytosin arabinoside in 1. The patients were diagnosed as having leukoencephalopathy (8), cerebrovascular injury (4), and Wernicke's encephalopathy (1). Symptomatic epilepsy was found in one patient, and mental retardation was seen in three patients during a 2-year course of treatment. We conclude that careful management is required in the treatment of acute lymphocytic leukemia, because of the persistence of neurological complications, although their severity is decreasing with advances in treatment.

Adolescent↗

[Intrapulmonary bronchogenic cysts].

Bronchogenic cysts are commonly found in the mediastinum, but occasionally in lung parenchyma. We report 3 patients with intrapulmonary bronchogenic cysts. A female presented back pain and a large cystic lesion with an air-fluid level on chest X-ray and computed tomography (CT). Another female was asymptomatic. A well-defined round mass with soft tissue intensity on magnetic resonance imaging (MRI) was found. A girl with repeated pulmonary infection and treatment in hospital for several years presented pulmonary infiltrate, air-fluid level, and oval linear shadow on X-rays. All patients underwent lobectomy because of the size and the non-anatomical location of their lesions. Definite diagnosis on their lesions was determined by pathological study. Several small communications between the cyst and adjunctive parenchyma was found in the symptomatic girl, while the cyst was isolated from surrounding parenchyma in the asymptomatic female. We suggest symptoms and various presentations on imaging modalities in patients with intrapulmonary bronchogenic cysts might relate to the amount of original communication between their cysts and native lung.

Adolescent↗

Utilization of mammalian cells for efficient and reliable evaluation of specificity of antibodies to unravel the cellular function of mKIAA proteins.

Complementary DNA (cDNA) clones for human KIAA genes have been isolated as long cDNAs (>4 kb) with unknown functions. To facilitate the functional analysis of these human clones, we have isolated and determined the structures of their respective mouse homologues (mKIAA genes). Furthermore, we have comprehensively raised antibodies against the translated mKIAA proteins in order to establish a platform for their functional analysis. Since the specificity of these antibodies is critical for subsequent analyses of protein function, here we introduce two assays utilizing mammalian cells to improve their evaluation. First, we have established a semi-high-throughput production of C-terminally FLAG epitope-tagged proteins for Western blotting using specially designed mammalian expression vectors. Secondly, we have utilized immunofluorescence staining of mouse cells to analyze the subcellular localization of endogenous mKIAA proteins. Importantly, these methods allow us to detect potential posttranslational modification of the mKIAA/KIAA proteins and to predict their biological function based on their subcellular localization.

Animals↗

Simultaneous analysis of termiticides in indoor air by using gas chromatography mass spectrometry.

We have established a method for simultaneously analyzing termiticides (13 kinds) in indoor air based on collection by combination of quartz filter and C18 Empore extraction disks, and measurement using gas chromatography mass spectrometry (GC/MS). The lower limit of determination for each substance was 0.02 microg/m3 when 2 m3 of air was sampled. The recovery was 66-100%, and the relative standard deviation was 3.7-14.2%. In experiments using a model box with commercial termiticides, we verified that emissions of bis (2, 3, 3, 3-tetrachloropropyl) ether (S421) increased with a rise in temperature from 10 degrees C to 20 degrees C to 40 degrees C, whereas almost no etofenprox was released into the air regardless of temperature. In addition, decanal, nonanal and alkanes (C13 and C14), which are major components of termiticides, were detected in relatively high concentrations. In the present study, regardless of low vapor pressure of the termiticides, several compounds were detected with the model box experiment. The conclusion that can be drawn is that it is necessary to survey the indoor environmental pollution.

Air Pollutants↗

Surgical treatment of thoracic aortic aneurysm in patients with concomitant coronary artery disease.

OBJECTIVE: Surgical treatment of thoracic aortic surgery in patients with coronary artery disease was investigated. METHODS: Between 1990 and April 2003, 330 patients underwent elective thoracic aortic surgery. Fifty-six patients who underwent aortic root reconstruction were excluded and 274 patients were examined. Fifty-four (20%) patients showed concomitant coronary artery disease. Ten had undergone coronary revascularization previously; and 3 underwent coronary revascularization [2 coronary artery bypass grafting (CABG), 1 percutaneous transluminal coronary angioplasty (PTCA)] before aortic surgery. Twenty-three patients underwent elective CABG simultaneously and 2 patients had additional coronary artery bypass because of cardiac ischemia during operation. The number of patients who underwent thoracic aortic surgery including Asc Ao+AVR was 2, hemi arch 1, total arch 15, distal arch 5, distal arch+LV aneurysmectomy 1, and thoracoabdominal Ao 1. Two patients underwent coronary revascularization with arterial grafts and the others with SVG grafts. RESULTS: There was one hospital death (4%). In patients without coronary bypass, 2 patients suffered cardiac ischemic events. CONCLUSION: Our thoracic aortic operations with concomitant CABG using SVG were overall successful. Our current strategies for thoracic aortic surgery in patients with concomitant coronary artery disease include conducting a dipyridamole myocardial perfusion-imaging test first in patients not at risk of coronary artery disease, and if the test is positive, coronary angiography is performed and aggressive coronary revascularization is conducted where possible.

Aged↗

Preparation of a set of expression-ready clones of mammalian long cDNAs encoding large proteins by the ORF trap cloning method.

Although we have so far identified and sequenced >2000 human long cDNAs, known as KIAA cDNAs, half of them have yet to be functionally annotated. Expression-ready cDNA clones derived from these genes, where the open reading frame (ORF) of the gene of interest is placed under the control of an appropriate promoter, are critical for functional characterization of these gene products. In this study, we attempted to systematically convert original cDNA clones to expression-ready forms for native and fusion proteins. For this purpose, we developed a new method for ORF cloning based on a homologous recombination in Escherichia coli to avoid laborious manipulations and artificial introduction of mutations in ORF. Using 1589 putative full-length ORFs (from 1002 KIAA genes, 119 human known genes and 468 mouse genes) with an average size of 2.8 kb, we successfully prepared expression plasmids for 1463 native proteins and for 1343 fusion proteins by this method. The resultant expression-ready clones were examined using an in vitro transcription/translation system followed by SDS-polyacrylamide gel electrophoresis and by transient expression of GFP-fusion proteins in human embryonic kidney (HEK) 293 cells. This set of expression-ready clones of long cDNAs encoding large proteins would open a new route to experimentally analyze their functions on a proteomic scale, since unavailability of expression-ready clones for mammalian large proteins has been a major obstacle to the functional analysis of these cDNAs.

Animals↗

[Image-guided endoscopic sinus surgery: a comparison of two navigation systems].

We evaluated the effectiveness of two navigation systems with optical tracking in endoscopic sinus surgery (ESS). The Signa SP/i Intraoperative navigation system (General Electric Co., Intraoperative NS) is advantageous in acquiring both real time and high-resolution images during surgery, compared to conventional image-guided navigation (Stealth Station TREON, Medtronic Inc., IGNS) that rely entirely on preoperative three-dimensional images. We studied the following in 14 patients treated with intraoperative NS and 19 treated with IGNS: 1) additional time for navigation system implementation, 2) available instrumentations in ESS, and 3) navigation system accuracy. Navigation systems required additional time to prepare ESS. The time lapse from admittance to the operating room to ESS onset was measured in patients under both systems and controls undergoing ESS without any image guidance. Preparation of the intraoperative NS required an additional 52 min and IGNS required 17 min compared to the control group. Based on operative instruments, the intraoperative NS has some limitations arising from the application of a high magnetic field. Surgical instruments must not be attracted by the magnetic field in the operating room. So those used in our study were thoroughly examined and some remanufactured using MR safe materials. All instruments in ESS could be used in surgical guidance during surgery in the IGNS. Anatomic landmarks were accurately visualized using intraoperative NS and IGNS. Intraoperative NS renews the image during surgery, so surgeons could confirm the surgical outcome during ESS. Since the average distant error in both systems was between 1 mm and 2.5 mm, we confirmed that accuracy obtained with both navigation system was suitable for ESS completion. The intraoperative NS renewed the image during navigation. In conclusion, both navigation systems are sufficient for accurate image navigation in ESS, but navigation systems must be selected based on the individual case.

Endoscopy↗

[Long-term remission in an acute monoblastic leukemia patient with down syndrome after cord blood transplantation].

A 4-year-old boy with Down syndrome (DS) was diagnosed as having acute monoblastic leukemia (AML-M5a). Leukemic cells were CD33+, CD56+ and CD4+, with t(9;11) on cytogenetic analysis and MLL gene rearrangement. After 2 courses of induction therapy using an AML 99-Down protocol failed to obtain complete remission, the patient received cord blood transplantation from an HLA-matched donor (CBT) following a conditioning regimen comprising total body irradiation and cyclophosphamide. Only cyclosporin A was used for graft-versus-host disease prophylaxis. Stem cell transplantation may not be indicated for AML patient with DS in first remission, who display a high rate of life-threatening and fatal toxicity on therapy. This patient remained well controlled in complete remission for 4 years, representing a rare case of DS with chemotherapy-resistant AML successfully treated with a CBT.

Child, Preschool↗

Tumor-promoting activity and mutagenicity of 5 termiticide compounds.

The tumor-promoting activities of 5 commercial compounds used in termiticides were measured by a cell-transformation assay employing Bhas 42 cells. Their initiating activities were also measured by the microsuspension assay employing S. typhimurium TA98 and TA100 strains. The results of the transformation assay confirmed the tumor-promoting activities of fenitrothion, silafluofen and bifenthrin. Furthermore, the mutagenicity of S-421 and fenitrothion were also confirmed. Consideration of 2-stage carcinogenesis suggests that concurrent use of and long-term exposure to these compounds that have tumor-promoting and initiator activity, and compounds exhibiting either type of activity individually should be avoided as much as possible.

Biotransformation↗

A comprehensive approach for establishment of the platform to analyze functions of KIAA proteins II: public release of inaugural version of InGaP database containing gene/protein expression profiles for 127 mouse KIAA genes/proteins.

The inaugural version of the InGaP database (Integrative Gene and Protein expression database; http://www.kazusa.or.jp/ingap/index.html) is a comprehensive database of gene/protein expression profiles of 127 mKIAA genes/proteins related to hypothetical ones obtained in our ongoing cDNA project. Information about each gene/protein consists of cDNA microarray analysis, subcellular localization of the ectopically expressed gene, and experimental data using anti-mKIAA antibody such as Western blotting and immunohistochemical analyses. KIAA cDNAs and their mouse counterparts, mKIAA cDNAs, were mainly isolated from cDNA libraries derived from brain tissues, thus we expect our database to contribute to the field of neuroscience. In fact, cDNA microarray analysis revealed that nearly half of our gene collection is predominantly expressed in brain tissues. Immunohistochemical analysis of the mouse brain provides functional insight into the specific area and/or cell type of the brain. This database will be a resource for the neuroscience community by seamlessly integrating the genomic and proteomic information about the mouse KIAA genes/proteins.

Animals↗

Identification of the genes that are expressed in the upper layers of the neocortex.

Laminar specificity is one of the most striking features of neocortical circuitry. To explore the molecular basis of this specificity, particularly in relation to thalamocortical connectivity, we searched for the genes expressed in the upper cortical layers by constructing a subtraction cDNA library that was enriched for genes expressed in layer 4 of perinatal rat somatosensory cortex. Differential screening, sequence analysis and in situ hybridization demonstrated that a new unc5 family member (unc5h4), deltex-like gene, stem cell factor (SCF) and myocyte-specific enhancer factor-2C (MEF-2C) were specifically expressed in layer 4 or layers 2/3-4 at postnatal day 7, by when laminar organization and fundamental cortical circuitries have been established. In terms of regional specificity, unc5h4 and SCF signals were stronger in sensory cortices, whereas MEF-2C and deltex-like gene were expressed rather uniformly in all neocortical regions. Analysis during development demonstrated that expression of these genes was pronounced between late embryonic and early postnatal developmental stages, except for MEF-2C expression, which continued in later stages. These results demonstrate that certain types of molecules including transcription factors, receptor and ligand molecules, are expressed specifically in the upper layers of the developing neocortex, suggesting a role in laminar specification of cortical cells and circuitry.

Amino Acid Sequence↗

Cloning of a novel signaling molecule, AMSH-2, that potentiates transforming growth factor beta signaling.

BACKGROUND: Transforming growth factor-betas (TGF-betas), bone morphogenetic proteins (BMPs) and activins are important regulators of developmental cell growth and differentiation. Signaling by these factors is mediated chiefly by the Smad family of latent transcription factors. RESULTS: There are a large number of uncharacterized cDNA clones that code for novel proteins with homology to known signaling molecules. We have identified a novel molecule from the HUGE database that is related to a previously known molecule, AMSH (associated molecule with the SH3 domain of STAM), an adapter shown to be involved in BMP signaling. Both of these molecules contain a coiled-coil domain located within the amino-terminus region and a JAB (Domain in Jun kinase activation domain binding protein and proteasomal subunits) domain at the carboxy-terminus. We show that this novel molecule, which we have designated AMSH-2, is widely expressed and its overexpression potentiates activation of TGF-beta-dependent promoters. Coimmunoprecipitation studies indicated that Smad7 and Smad2, but not Smad3 or 4, interact with AMSH-2. We show that overexpression of AMSH-2 decreases the inhibitory effect of Smad7 on TGF-beta signaling. Finally, we demonstrate that knocking down AMSH-2 expression by RNA interference decreases the activation of 3TP-lux reporter in response to TGF-beta. CONCLUSIONS: This report implicates AMSH and AMSH-2 as a novel family of molecules that positively regulate the TGF-beta signaling pathway. Our results suggest that this effect could be partially explained by AMSH-2 mediated decrease of the action of Smad7 on TGF-beta signaling pathway.

Adaptor Proteins, Signal Transducing↗

HUGE: a database for human KIAA proteins, a 2004 update integrating HUGEppi and ROUGE.

We have been developing a Human Unidentified Gene-Encoded (HUGE) protein database (http://www.kazusa.or.jp/huge) to summarize results from sequence analysis of human novel large (>4 kb) cDNAs identified in the Kazusa cDNA sequencing project. At present, HUGE contains 2031 cDNA entries (KIAA cDNAs), for each of which a gene/protein characteristic table has been prepared. Since we have been shifting our research attention from the identification and cloning of novel cDNAs to the functional analysis of the proteins encoded by these cDNAs (KIAA proteins), we have not substantially increased the number of cDNA entries in HUGE for some time. Instead, we have manually curated 451 KIAA cDNAs in order to prepare a set of genetic resources to facilitate the functional analysis of KIAA proteins. In addition, we have updated the contents of the corresponding gene/protein characteristic tables in HUGE and have constructed two subsidiary databases, HUGEppi (http://www. kazusa.or.jp/huge/ppi) and ROUGE (http://www. kazusa.or.jp/rouge), to make available the results from our study of KIAA protein function. HUGEppi shows detailed information on protein-protein interactions detected between 84 pairs of KIAA proteins by yeast two-hybrid screening. ROUGE summarizes the results of computer-assisted analyses of approximately 1000 mouse homologues of human large cDNAs that we identified.

Animals↗