Search PubMed⌕ Search

Biomedical subjects

T Nakajima

Publications and source records attributed to T Nakajima.

At least 19 recordsLinked to original sources
PubMed2006

Sarin experiences in Japan: acute toxicity and long-term effects.

Two terrorist attacks with the nerve agent Sarin affected citizens in Matsumoto and Tokyo, Japan in 1994 and 1995, killing 19 and injuring more the 6000. Sarin, a very potent organophosphate nerve agent, inhibits acetylcholinesterase (AchE) activity within the central, peripheral, and autonomic nervous systems. Acute and long-term Sarin effects upon humans were well documented in these two events. Sarin gas inhalation caused instantaneous death by respiratory arrest in 4 victims in Matsumoto. In Tokyo, two died in station yards and another ten victims died in hospitals within a few hours to 3 months after poisoning. Six victims with serum ChE below 20% of the lowest normal were resuscitated from cardiopulmonary arrest (CPA) or coma with generalized convulsion. Five recovered completely and one remained in vegetative state due to anoxic brain damage. EEG abnormalities persisted for up to 5 years. Miosis and copious secretions from the respiratory and GI tracts (muscarinic effects) were common in severely to slightly affected victims. Weakness and twitches of muscles (nicotinic effects) appeared in severely affected victims. Neuropathy and ataxia were observed in small number (less than 10%) of victims, which findings disappeared between 3 days and 3 months. Leukocytosis and high serum CK levels were common. Hyperglycemia, ketonuria, low serum triglyceride, hypopotassemia were observed in severely affected victims, which abnormalities were attributed to damage of the adrenal medulla. Oximes, atropine sulphate, diazepam and ample intravenous infusion were effective treatments. Pralidoxime iodide IV reversed cholinesterase and symptoms quickly even if administered 6 h after exposure. Post Traumatic Stress Disorder (PTSD) was less than 8% after 5 years. However, psychological symptoms continue in victims of both incidents. In summary, both potent toxicity and quick recovery from critical ill conditions were prominent features. Conventional therapies proved effective in Sarin incidents in Japan.

Acute Disease↗
PubMed2006

Phase separation in A-site-ordered perovskite manganite LaBaMn2O6 probed by 139La and 55Mn NMR.

139La- and 55Mn-NMR spectra demonstrate that the ground state of the A-site-ordered perovskite manganite LaBaMn2O6 is a spatial mixture of the ferromagnetic and antiferromagnetic regions, which are assigned to the metallic and the insulating charge ordered state, respectively. This exotic coexisting state appears below 200 K via a first-order-like formation of the antiferromagnetic charge ordered state inside the ferromagnetic metal one. The Mn spin-spin relaxation rate indicates that the ferromagnetic region coexisting with the antiferromagnetic one in LaBaMn2O6 is identical to the bulk ferromagnetic metal phase of the disordered form La0.5Ba0.5MnO3 in spite of the absence of A-site disorder. This suggests a mesoscopic rather than nanoscopic nature of the ferromagnetic region in LaBaMn2O6.

Journal Article↗
PubMed2006

Increased infiltration of CD1d and natural killer T cells in periodontal disease tissues.

BACKGROUND: Natural killer T (NKT) cells are a unique T lymphocyte subset that has been implicated in the regulation of immune responses associated with a broad range of diseases including autoimmunity, infectious diseases, and cancer. In contrast to conventional T cells, NKT cells are reactive to major histocompatibility complex (MHC) class I-like molecule CD1d. Considering the periodontitis having both aspects of infection and autoimmunity in nature, CD1d and reactive NKT cells are of particular importance. OBJECTIVE: The aim of the present study was to examine whether the expression of CD1 isoforms and Valpha24(+) invariant NKT cells is associated with different disease entities, namely gingivitis and periodontitis. MATERIAL AND METHODS: Immunohistochemical analysis was performed on cryostat sections of gingival tissues from 19 patients with periodontitis and eight patients with gingivitis using antibodies to CD1a, b, c, d, Valpha24(+) invariant NKT cells, CD83, CD3 and CD19. RESULTS: Although all four subsets of CD1 molecules were expressed in periodontal lesions, CD1d was most abundant. CD1d expression was more frequent in periodontitis than gingivitis and increased together with increase of invariant NKT cell infiltration. Double immunohistochemical staining showed co-expression of CD1d and CD19 on identical cells and proximate infiltration of CD1d(+) and invariant NKT cells. CONCLUSION: These findings suggest that CD1d-expressing B cells could activate NKT cells by CD1d-restricted manner and this NKT cell activation may play roles in pathogenesis of periodontal diseases.

Adult↗
PubMed2006

Limitation of cigarette consumption by CYP2A6*4, *7 and *9 polymorphisms.

The whole gene deletion CYP2A6*4, the defect of the main nicotine oxidase, contributes to limiting lifelong and daily cigarette consumption. However, the effects on smoking habits of CYP2A6*7 and *9, two major functional polymorphisms common in Asian populations, have not been reported. The present study examined the relationship between polymorphisms *4, *7 and *9 with the smoking habits of 200 Japanese smokers who visited the Keio University Hospital (Tokyo, Japan). The allele frequencies of *1 (wild type), *4, *7 and *9 were 52, 17, 11 and 20%, respectively. When the three polymorphisms were considered simultaneously, the percentages of homozygous wild type, heterozygote, and homozygous mutants and compound heterozygotes were 26.0, 52.5 and 21.5%, respectively. Homozygous mutants and compound heterozygotes (n = 43) smoked fewer cigarettes daily than heterozygotes (n = 105) and homozygous wild-type individuals (n = 52). Smokers with *7/*7, *9/*9 or *7/*9 had lower daily cigarette consumption than smokers with *1/*1. In conclusion, polymorphisms *4, *7 and *9 of CYP2A6 were detected in approximately three out of four Japanese smokers, and their daily cigarette consumption was genetically modulated by these functional polymorphisms.

Aged↗
PubMed2006

Predictors of long-term survival with pulmonary metastasectomy for osteosarcomas and soft tissue sarcomas.

AIM: The control of pulmonary metastases is important for long-term survival of the patients with osteosarcomas and soft tissue sarcomas. METHODS: To evaluate the efficacy of aggressive pulmonary metastasectomy for those patients, we reviewed 105 cases (44 osteosarcomas, and 61 soft tissue sarcomas) treated in our hospital. RESULTS: The number of metastases was only the significant risk factor for the curability of the metastasectomy (logistic regression analysis, P=0.0274). The 5-year and 10-year survival rate were 43.6% and 32%. The curability was only independent prognostic factor on multivariate analysis (P=0.0008). CONCLUSIONS: Early detection of pulmonary metastasis, multimodal perioperative treatment, and design for minimizing the volume of resected lung tissues will enable complete and repeat resections for the achievement of long-term survival.

Adolescent↗
PubMed2005

A green tea polyphenol, epigalocatechin-3-gallate, induces apoptosis of human hepatocellular carcinoma, possibly through inhibition of Bcl-2 family proteins.

BACKGROUND/AIMS: A major polyphenol of green tea, epigallocatechin-3-gallate (EGCG), has previously been shown to induce cell-cycle arrest and apoptosis in various cancers. However, little is known about its effects on hepatocellular carcinomas (HCCs). METHODS: Four HCC cell lines, HLE, HepG2, HuH-7 and PLC/PRF/5, were treated with EGCG or vehicle. Cell viability was assessed by trypan blue staining and WST-8 assay. Cell-cycle, apoptosis and apoptosis-related proteins in HLE cells were evaluated by flow cytometry and Western blotting. The effect of EGCG was also studied in vivo using a xenograft model. The effect of co-treatment with EGCG and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was also assessed. RESULTS: EGCG inhibited the growth of all HCC cell lines at concentrations of 50-100 microg/ml. In HLE cells, EGCG induced apoptosis but not cell-cycle arrest and appears to have down-regulated Bcl-2alpha and Bcl-xl by inactivation of NF-kappaB. Oral administration of EGCG showed similar effects in HLE xenograft tumors. Co-treatment with EGCG and TRAIL synergistically induced apoptosis in HLE cells. CONCLUSIONS: EGCG induced apoptosis in HLE cells, both in vitro and in vivo. Moreover, it enhanced TRAIL-induced apoptosis. Therefore, EGCG treatment may be useful for improving the prognosis of HCCs.

Administration, Oral↗
PubMed2005

Involvement of Egr-1 in lens epithelial cell death induced by selenite.

Selenite-overdose cataract in young rats may be caused by an initial insult to the lens epithelial cells. Our previous DNA array analysis revealed a significant increase in the expression of mRNA for early growth response protein-1 (Egr-1) in lens epithelial cells after injection of selenite. This suggested that up-regulation of Egr-1 mRNA may be involved in lens epithelial cell death. The purpose of the present experiment was to further clarify the involvement of Egr-1 in lens epithelial cell death induced by selenite. Rat lens epithelial explants were cultured with sodium selenite. Selenite caused epithelial explants to leak LDH into the medium. During LDH leakage, increased expression of mRNA for Egr-1 was observed by RT-PCR. To further test the involvement of Egr-1 in selenite-induced cell death, mouse lens epithelial cell line (alpha-TN4 cells) was treated with antisense oligonucleotide for Egr-1. Antisense oligonucleotide for Egr-1 significantly diminished expression of Egr-1 protein and leakage of LDH. These results suggested that increased activity of Egr-1 may be a factor in lens epithelial cell death induced by selenite.

Animals↗
PubMed2005

Malignant transformation of pleomorphic xanthoastrocytoma.

A 31-year-old woman presented with a pleomorphic xantho-astrocytoma (PXA) manifesting as epilepsy. The tumour was partially resected. Histological examination revealed cellular pleomorphism and cytoplasmic vacuolation consistent with PXA, but no mitoses, necrosis, or endothelial proliferation. Follow-up neuro-imaging showed the residual tumour had grown rapidly with dissemination in the spinal cord. The recurrent lesion was totally resected and was shown to be glioblastoma. The patient has survived without signs of recurrence for 36 months after adjuvant radiochemotherapy. The biological behaviour of PXA cannot be predicted based on the histological features and careful follow up is essential.

Adult↗
PubMed2005

Solution structure of two insect-specific spider toxins and their pharmacological interaction with the insect voltage-gated Na+ channel.

Delta-paluIT1 and delta-paluIT2 are toxins purified from the venom of the spider Paracoelotes luctuosus. Similar in sequence to mu-agatoxins from Agelenopsis aperta, their pharmacological target is the voltage-gated insect sodium channel, of which they alter the inactivation properties in a way similar to alpha-scorpion toxins, but they bind on site 4 in a way similar to beta-scorpion toxins. We determined the solution structure of the two toxins by use of two-dimensional nuclear magnetic resonance (NMR) techniques followed by distance geometry and molecular dynamics. The structures of delta-paluIT1 and delta-paluIT2 belong to the inhibitory cystine knot structural family, i.e. a compact disulfide-bonded core from which four loops emerge. Delta-paluIT1 and delta-paluIT2 contain respectively two- and three-stranded anti-parallel beta-sheets as unique secondary structure. We compare the structure and the electrostatic anisotropy of those peptides to other sodium and calcium channel toxins, analyze the topological juxtaposition of key functional residues, and conclude that the recognition of insect voltage-gated sodium channels by these toxins involves the beta-sheet, in addition to loops I and IV. Besides the position of culprit residues on the molecular surface, difference in dipolar moment orientation is another determinant of receptor binding and biological activity differences. We also demonstrate by electrophysiological experiments on the cloned insect voltage-gated sodium channel, para, heterologuously co-expressed with the tipE subunit in Xenopus laevis oocytes, that delta-paluIT1 and delta-paluIT2 procure an increase of Na+ current. delta-PaluIT1-OH seems to have less effect when the same concentrations are used.

Animals↗
PubMed2005

Alpha-synuclein-positive structures induced in leupeptin-infused rats.

Abnormal accumulation of alpha-synuclein is regarded as a key pathological step in a wide range of neurodegenerative processes, not only in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) but also in multiple-system atrophy (MSA). Nevertheless, the mechanism of alpha-synuclein accumulation remains unclear. Leupeptin, a protease inhibitor, has been known to cause various neuropathological changes in vivo resembling those of aging or neurodegenerative processes in the human brain, including the accumulation of neuronal processes and neuronal cytoskeletal abnormalities leading to neurofibrillary tangle (NFT)-like formations. In the present study, we administered leupeptin into the rat ventricle and found that alpha-synuclein-positive structures appeared widely in the neuronal tissue, mainly in neuronal processes of the fimbria and alveus. Immunoelectron microscopic study revealed that alpha-synuclein immunoreactivity was located in the swollen axons of the fimbria and alveus, especially in the dilated presynaptic terminals. In addition colocalization of alpha-synuclein with ubiquitin was rarely observed in confocal laser-scan image. This is the first report of experimentally induced in vivo accumulation of alpha-synuclein in non-transgenic rodent brain injected with a well-characterized protease inhibitor by an infusion pump. The present finding suggests that the local accumulation of alpha-synuclein might be induced by the impaired metabolism of alpha-synuclein, which are likely related to lysosomal or ubiquitin-independent proteasomal systems.

Animals↗
PubMed2005

Attenuation of the effect of remote muscle contraction on the soleus H-reflex during plantar flexion.

OBJECTIVE: We investigated to what extent the facilitation of the soleus (Sol) Hoffmann (H-) reflex during a phasic voluntary wrist flexion (Jendrássik maneuver, JM) can be modulated by graded plantar flexion force and conditioning wrist flexion force. METHODS: The subjects were asked to perform phasic wrist flexion under a reaction time condition. Sol H-reflex was evoked by stimulating the right tibial nerve at various time intervals (50-400ms) after the 'Go' signal for initiating JM while the ankle was at rest and while plantarflexing. The level of tonic plantar flexion force (isometric contraction of 10, 20 and 30% of maximal EMG) and conditioning wrist flexion (isometric contraction of 30, 50 and 80% of maximum voluntary contraction) during JM was graded systematically. RESULTS: Although JM facilitation could be seen 80-120ms after the flexor carpi radialis (FCR) EMG onset even while plantarflexing, the magnitude of JM facilitation under plantar flexion was significantly decreased compared to that at rest. The degree of decrease in JM facilitation did not depend on the level of plantar flexion force. In contrast, the degree of JM facilitation was proportional to the level of wrist flexion force while the ankle was at rest and while plantarflexing, though the amount of JM facilitation significantly decreased while plantarflexing. CONCLUSIONS: JM facilitation of Sol H-reflex is decreased while performing tonic voluntary contraction of the homonymous muscle. The degree of decrease in JM facilitation is independent of the level of homonymous muscle contraction, but depends on the level of remote FCR contraction. In clinical application, when we intend to elicit a maximum stretch reflex by JM, full relaxation of homonymous muscle should be carefully confirmed. SIGNIFICANCE: Our results provide evidence for better understanding of the features of JM and insight into its clinical application.

Acoustic Stimulation↗
PubMed2005

Progesterone induces the fibulin-1 expression in human endometrial stromal cells.

BACKGROUND: By using microarray analysis with human endometrial stromal cells (ESCs), we previously reported that the mRNA for fibulin-1, an extracellular matrix as well as a plasma glycoprotein, is up-regulated by progesterone. In the present study, we tried to clarify the spatial and temporal regulation mechanism of fibulin-1 in the human endometrium. METHODS AND RESULTS: Quantitative analysis with real-time PCR experiments on human endometrial tissues showed significantly higher fibulin-1 mRNA expressions in secretory phase endometria than in proliferative phase. Immunohistochemical studies revealed that the fibulin-1 protein is expressed in the glandular epithelium in proliferative phase endometria, and that expression switched to the stroma in secretory phase endometria. In culture experiments with ESCs, a significant increase of fibulin-1 mRNA expression was observed in cells treated with 6 alpha-methyl-17 alpha-hydroxy-progesterone acetate (MPA) or 8 bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP). MPA stimulated the fibulin-1 mRNA expression in a dose-dependent manner, and a progesterone antagonist, RU-486, inhibited the stimulatory effect almost completely. By contrast, beta-estradiol alone did not increase the fibulin-1 mRNA expression. CONCLUSIONS: These results suggest that fiblin-1 is an important molecule that mediates progesterone action in human ESC differentiation towards implantation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2005

Insertion and excision of a transposable element governs the red floral phenotype in commercial petunias.

Commercial cultivars of Petunia hybrida with red flowers (red petunias) accumulate cyanidin 3-glucoside as a main floral anthocyanin pigment. The conversion of anthocyanidin 3-glucosides to anthocyanidin 3-rutinosides is catalyzed by a UDP-rhamnose: anthocyanidin 3-glucoside-rhamnosyltransferase (RT). In red petunias, the RT gene is known to be disrupted by the insertion of a transposable element (dTph3). We have cloned the dTph3-like element (called dTph3-C) from a red petunia. Unlike dTph3, dTph3-C harbored a perfect terminal inverted repeat. In addition, an excision product (so-called "footprint") of dTph3/dTph3-C was found in another red petunia. The RT transcripts harboring this footprint could not produce the RT enzyme because a stop codon was created in the footprint sequence. The genotypes of the 42 commercial petunias which exhibit different anthocyanin pigmentation were determined by multiplex PCR. In this technique, the amplified products from normal, dTph3/dTph3-C-inserted, and footprint-retaining RT genes can be separated from one another. Our results indicate that the red-floral phenotype of commercial petunias is governed by insertion and excision events of a transposable element in the coding region of the RT gene.

Anthocyanins↗
PubMed2005

Daily profile of plasma %CoQ10 level, a biomarker of oxidative stress, in patients with diabetes manifesting postprandial hyperglycaemia.

The purpose of this study was to investigate the effect of regular meals on the daily profile of blood oxidative stress markers in type 2 diabetic patients with postprandial hyperglycaemia. %CoQ10, calculated as the ratio of ubiquinone-10 (oxidised form of coenzyme Q10) to ubiquinol-10 (reduced form), was used as a sensitive marker of oxidative stress. Blood samples were collected from patients before and 2 h after breakfast, lunch and supper, and at 10 p.m. Patients were selected for the study if their blood glucose levels were <7 mmol/l before breakfast and > or =11.1 mmol/l on at least one occasion after breakfast. %CoQ10 levels after breakfast and throughout the day were significantly higher than those before breakfast (p=0.006-0.04). In contrast to the wave-like changes in plasma glucose levels, %CoQ10 levels increased after breakfast and remained at high levels throughout the day. These results indicated that diabetic patients with postprandial hyperglycaemia were exposed to meal-induced periods of oxidative stress during the day. Postprandial hyperglycaemia therefore has the potential to increase the risk of atherosclerotic cardiovascular disease through induction of oxidative stress.

Ascorbic Acid↗
PubMed2005

Simultaneous multi-section perfusion CT and CT angiography for the assessment of acute ischemic stroke.

BACKGROUND: Introduction of helical computed tomography (CT) scanning has enabled rapid imaging of the vascular status by means of CT angiography and perfusion CT. By virtue of recent multi-detector technology, helical CT has the ability to perform both CT angiography and multi-section perfusion CT simultaneously. This study investigated the clinical feasibility of simultaneous assessment of perfusion CT and CT angiography in patients with acute ischemic stroke. METHOD: Perfusion CT and CT angiography were performed simultaneously in a series of consecutive 31 acute ischemic stroke patients. The time required for the entire processing was about 15 minutes. Contrast agent was used in a total dose of 100 ml (35 ml for perfusion CT and 65 ml for CT angiography). FINDINGS: Simultaneous perfusion CT scans and CT angiographies were of diagnostic quality for 29 patients (94%). In large territorial infarct patients, perfusion CT could predict all perfusion deficits of the final lesions (10 out of 10 lesions) and CT angiography could detect 9 of 10 occlusions of major cerebral arteries (90%). In patients with small lacunar or subcortical infarcts, perfusion CT could predict 9 out of 19 lesions (47.4%), and false-negative were encountered in small lesions (three patients) or in inadequate coverage of data acquisition (seven patients). Acute stage thrombolytic intervention could be carried out based on the findings, and the success of thrombolytic therapy could be demonstrated by follow-up study. CONCLUSIONS: Simultaneous perfusion CT and CT angiography is the very useful tool for the rapid and adequate diagnosis of almost all of the large territorial infarcts and some of non-territorial lacunar infarcts. It is an easy-to-perform and safe imaging technique to assess acute ischemic stroke.

Acute Disease↗
PubMed2005

The change in the appearance of the vermilion border region caused by the difference of the design in symmetric bilateral incomplete cleft lip repair.

In the widely performed methods for repair of bilateral cleft lips, such as Mulliken and Trott methods, the formation of the median tubercle is done with the mucocutaneous flaps from the lateral lips. By this manoeuver, a visible horizontal scar just above the white skin roll of the philtral region tends to result, especially among Asian patients. To avoid the formation of this visible scar, we changed our design in such a way that mucosal flaps, instead of mucocutaneous flaps, are elevated from the lateral lips, and the prolabial white skin roll is preserved to become the final philtral white skin roll. By this change in design, the horizontal scar is shifted to the inferior edge of the vermilion border. In the past 8 years, we have performed this refined method along with the conventional one. In the present study, the five cases of symmetric bilateral incomplete cleft lip from each of the two groups are evaluated: one group with the mucocutaneous flaps and the other with the mucosal flaps. From the review of the cases, it was noted that when the philtral region is formed with the mucocutaneous flaps, the horizontal scar tends to be visible. On the other hand, when it is formed with the mucosal flaps, the scar is less conspicuous, although the white skin roll sometimes becomes less-defined. The refined method involving mucosal flaps from the lateral lips produces a better-accepted appearance concerning the prolabial horizontal scar in the symmetric bilateral incomplete cleft lip repair.

Child, Preschool↗
PubMed2005

Evidence for natural selection in the HAVCR1 gene: high degree of amino-acid variability in the mucin domain of human HAVCR1 protein.

The family of genes encoding T-cell immunoglobulin and mucin-domain containing proteins (Tim), which are cell-surface molecules expressed in CD4(+) T helper cells, has important roles in the immune system. Here, we report three unusual patterns of genetic variation in the human hepatitis A virus cellular receptor 1 gene (HAVCR1) that are similar to patterns observed in major histocompatibility complex loci. First, levels of polymorphism in exon 4 of HAVCR1 were exceptionally high in humans (nucleotide diversity (pi)=45.45 x 10(-4)). Second, nonsynonymous substitutions and insertion/deletion variants were more frequent than synonymous substitutions in that exon (10 out of 12 variants). The rate of the mean number of nucleotide substitutions at nonsynonymous sites to synonymous sites at HAVCR1-exon 4 is >1 (P(A)/P(S)=1.92 and pi(A)/pi(S)=2.23). Third, levels of divergence among human, chimp, and gorilla sequences were unusually high in HAVCR1-exon 4 sequences. These features suggest that patterns of variation in HAVCR1 have been shaped by both positive and balancing natural selection in the course of primate evolution. Evidence that the effects of natural selection are largely restricted to the mucin domain of HAVCR1 suggests that this region may be of particular evolutionary and epidemiological interest.

Base Sequence↗