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Biomedical subjects

Shigeru Tanaka

Publications and source records attributed to Shigeru Tanaka.

At least 37 records · Page 2Linked to original sources

Visceral pleural perforation in two cases of ultrathin bronchoscopy.

Recently, ultrathin bronchoscopes with a thinner external diameter, greater visual range, improved visibility, and a larger working channel have been developed. The utility of a 2.8-mm diameter ultrathin bronchoscope in diagnosing peripheral pulmonary nodules has been reported by some authors. While the feasibility of approaching peripheral pulmonary lesions is attractive, peculiar complications that have not been experienced with standard bronchoscopy may occur. We report two cases in which pneumothoraces occurred because their visceral pleuras were perforated with an ultrathin bronchoscope during the procedure. The peculiar mechanism of pneumothorax in relation to ultrathin bronchoscopy is discussed.

Aged↗

The Gs-linked receptor GPR3 maintains meiotic arrest in mammalian oocytes.

Mammalian oocytes are held in prophase arrest by an unknown signal from the surrounding somatic cells. Here we show that the orphan Gs-linked receptor GPR3, which is localized in the oocyte, maintains this arrest. Oocytes from Gpr3 knockout mice resume meiosis within antral follicles, independently of an increase in luteinizing hormone, and this phenotype can be reversed by injection of Gpr3 RNA into the oocytes. Thus, the GPR3 receptor is a link in communication between the somatic cells and oocyte of the ovarian follicle and is crucial for the regulation of meiosis.

Adenylyl Cyclases↗

The impact of volcanic gases from Miyake island on the chemical constituents in precipitation in the Tokyo metropolitan area.

The volcano on Miyake Island first erupted in July 2000 and continuous emission of volcanic gas from the collapsed caldera has been observed from the middle of August 2000. The large volcanic emission of SO2 had a strong influence on Tokyo metropolitan area, which is located approximately 150 km north of Miyake Island. We measured major ions in precipitation and dry deposition samples which had been collected at five sampling sites (Yokohama, Kashiwa, Fujisawa, Yokosuka, and Hachioji) in the Tokyo metropolitan area for 12 years since 1990. We have evaluated quantitatively the impact of the volcanic SO2 gas emitted from Miyake Island on the Tokyo metropolitan area by comparing depositional ionic constituents in the volcanic degassing period (from September 2000 to August 2001) with those in the normal period of the past 10 years (September 1990 to August 2000). nss-SO4(2-) concentrations in precipitation at the sampling sites in the Tokyo metropolitan area were 59.5-77.0 microeq/L during the degassing period, and 33.3-44.1 microeq/L during the normal period, respectively. The difference of nss-SO4(2-) concentrations between the two periods was statistically significant. In contrast, no significant differences were observed in the concentrations of the other major ions (NH4+, nss-Ca2+, Cl-, and NO3-) between the two periods. The impact of volcanic degassing from Miyake Island on the ionic concentrations in the precipitation of the Tokyo metropolitan area was seen only in the H+ and nss-SO4(2-) concentrations. The annual wet deposition amount of volcanic nss-SO4(2-) into the Tokyo metropolitan area has been quantitatively estimated. The annual wet deposition amounts were calculated as 701+/-277 Meq/year (22.4+/-8.9 kt SO2/year) on the total area of the Tokyo metropolitan area (14,000 km2). The wet deposition amount of nss-SO4(2-) corresponds to only 0.15% of the total annual amount of volcanic SO2 (15 Mt/year) emitted from Miyake Island from September 2000 to August 2001. This estimation is consistent with a previous study which reported that 0.3% of the atmospheric discharge of SO2 from the volcano in Mt. Etna in Sicily was deposited by precipitation to the surrounding area (1200 km2). The annual wet deposition amount of volcanic SO2 to the Tokyo metropolitan area was at the same order of the magnitude (37+/-15%) as the annual anthropogenic SO2 amount (60 kt/year) emitted from the Tokyo metropolitan area.

Air Movements↗

Daily concentrations of trace metals in aerosols in Beijing, China, determined by using inductively coupled plasma mass spectrometry equipped with laser ablation analysis, and source identification of aerosols.

This paper describes the daily concentrations of trace metals and ionic constituents in the aerosol of Beijing, China from March 2001 to August 2003. Daily PM10 concentrations were also measured from September 2001 to August 2003. The daily average PM10 concentration at Beijing, China from September 2001 to August 2003 was 171+/-117 microg m(-3) (n = 673), which is 5-fold higher than at Yokohama, Japan. Trace metal concentrations were analyzed by using inductively coupled plasma mass spectrometry equipped with a laser ablation sample introduction (LA/ICP-MS), which is a rapid and simultaneous method for multi-element analysis. The daily average metal concentrations in TSP in Beijing from March 2001 to August 2003 were: Al: 3.5+/-2.4 (n = 727), Ti: 0.47+/-0.35 (n = 720), V: 0.013+/-0.010 (n = 716), Cr: 0.019+/-0.015 (n = 618), Mn: 0.24+/-0.16 (n = 730), Fe: 5.5+/-3.9 (n = 728), Co: 0.0046+/-0.0055 (n = 629), Ni: 0.022+/-0.024 (n = 680), Cu: 0.11+/-0.11 (n = 660), Zn: 0.77+/-0.60 (n = 726), As: 0.048+/-0.047 (n = 731), Se: 0.010+/-0.010 (n = 550), Cd: 0.0068+/-0.0082 (n = 709), Sb: 0.033+/-0.036 (n = 687), and Pb: 0.43+/-0.50 (n = 728) (unit, microg m(-3)). All the metal concentrations in TSP in Beijing, China were 1.7-21.8 times higher than those in TSP in the center of Tokyo, Japan. Notably, As concentrations in TSP in Beijing were 20-fold higher than those in Tokyo. Source identification of aerosols in Beijing was carried out by using the chemical mass balance (CMB) receptor model, with the daily concentration of metals in the aerosol. The major primary sources of the aerosol of Beijing were considered to be soil dust and coal combustion. Vehicle exhaust contribution tended to increase.

Journal Article↗

Infiltrating macrophages as in vivo targets for intravenous gene delivery in cerebral infarction.

BACKGROUND AND PURPOSE: Gene therapy may show promise for stroke patients, but invasive techniques such as intraventricular or intracerebral injection of therapeutic genes may have limited applicability. The purpose of this study is to develop systemic gene therapy using macrophages infiltrating the infarct to deliver and express the gene. METHODS: After permanent middle cerebral artery occlusion in rats, an enhanced green fluorescent protein (EGFP) plasmid conjugate in liposomes was injected via the femoral vein. We also constructed a bicistronic plasmid vector for fibroblast growth factor-2 (FGF-2) as well as EGFP, administering it in other rats with middle cerebral artery occlusion. RESULTS: EGFP expression in normal brain was absent but was strong in macrophages accumulating along the infarct border. FGF-2 protein production was induced in macrophages along the infarct border after injection of bicistronic FGF-2 and EGFP plasmid vector; this stimulated proliferation of neural progenitors in the subventricular zone in the ischemic hemisphere compared with control plasmid vectors (61.7+/-5.2 versus 42.2+/-5.5 cells per mm2, n=4 each, P<0.01). CONCLUSIONS: Systemic gene transfer by liposome to macrophages infiltrating an infarct may prove useful for gene therapy in stroke.

Animals↗

CRE-mediated gene transcription in the peri-infarct area after focal cerebral ischemia in mice.

Cyclic AMP response element binding protein (CREB) is a transcription factor expressed constitutively primarily in neurons and is activated by phosphorylation at Ser(133) residue. CREB mediates expression of several neuroprotective proteins, including B-cell CLL/lymphoma 2 (BCL-2) and brain-derived neurotrophic factor (BDNF). Although phosphorylation of CREB after ischemia has been investigated extensively, CRE-mediated gene transcription after ischemia is not as well studied. We investigated temporal changes in CRE-mediated gene transcription in the cerebral cortex after focal ischemia in transgenic mice with a CRE-lacZ reporter gene. In the ischemic core, X-gal-positive cells, which reflected expression of the CRE-lacZ reporter gene, were observed rarely at any time point, though transient phosphorylation of CREB was detected. In contrast, the peri-infarct area showed a persistent increase in the number of X-gal-positive cells, of which more than half were positive for neuronal nuclei (NeuN). Our results suggest that CRE-mediated gene transcription, the pattern of which is not always consistent with that of CREB phosphorylation, occurs primarily in neurons in the peri-infarct area after focal cerebral ischemia and may be a neuroprotective response against ischemic insult.

Animals↗

Orientation tuning and synchronization in the hypercolumn model.

The orientation selectivity in the firing rate of neurons is one of the most well-known properties of neurons in the primary visual cortex. To understand the dynamical mechanism of the orientation tuning, we introduce a biologically plausible network for a hypercolumn and investigate dynamical responses of its columnar activities. Numerical simulations show that the spike activities between excitatory cells in the same column exhibit strong synchronization and sharp orientation selectivity. The tuning curves for the synchronized activities also show orientation selectivity similar to those for the firing rate. The comparison between the two tuning curves for the firing rate and the synchronized activities suggests that the orientation selectivity is strongly correlated with the synchronized activities. We find from the analysis of columnar activities that the orientation selectivity depends strongly upon the inhibitory coupling strength and the synchronization upon the excitatory coupling strength. In particular, we find that at appropriate coupling parameters both sharp orientation selectivity and maximal synchronization can be achieved. This suggests the importance of the balance between the excitatory coupling and the inhibitory coupling in the primary visual cortex for visual information processing.

Action Potentials↗

Theoretical consideration of olfactory axon projection with an activity-dependent neural network model.

Olfactory sensory neurons (OSNs) that express a given odorant receptor (OR) target their axons onto a few specific glomeruli in the olfactory bulb. Although the odorant receptor plays an indispensable role in olfactory axon targeting, the mechanisms underlying this guidance are largely unknown. In particular, there is much controversy regarding the involvement of activity-dependent mechanism in the targeting process. In this study, we developed an activity-dependent self-organization model of the glomerular layer in the olfactory bulb and simulated the targeting of olfactory axons onto the layer. Our model successfully constructed discrete glomeruli that received olfactory axons expressing a common odorant receptor through odorant-evoked neural activities. Furthermore, our model explained the perplexing experimental results that have been reported in olfactory axon targeting. For example, dispersion of olfactory axons in knockout mice for the odorant receptor gene was reasonably reproduced in the simulation. The segregated projection of the axons that express the same odorant receptor transcribed from the different alleles was also successfully simulated if the genetically modified allele was assumed to express a smaller amount of the receptor protein. The activity-dependent model even explained the inconsistent effects of disruption of the activity-evoking ion channel on axons expressing different odorant receptors, although some of these results were regarded as evidence for activity-independency of the olfactory targeting. Taken together, the activity-dependent targeting of olfactory axons seems to be a simple probable mechanism that can provide a unified explanation of glomerular formation.

Action Potentials↗

Sound frequency representation in cat auditory cortex.

Using the intrinsic signal optical recording technique, we reconstructed the two-dimensional pattern of stimulus-evoked neuronal activities in the auditory cortex of anesthetized and paralyzed cats. The average magnitude of intrinsic signal in response to a pure tone stimulus increased steadily as the sound pressure level increased. A detailed analysis demonstrated that the evoked signals at early frames were scaled by the sound pressure level, which in turn indicated the presence of a minimum level of sound pressure beyond which stimulus-related intrinsic signal can be generated. Intrinsic signals evoked significantly by pure tone stimuli of different frequencies were localized and arranged in an orderly manner in the middle ectosylvian gyrus, which indicates that the primary auditory field (AI) is tonotopically organized. The arrangement of optimal frequencies obtained from optical recordings of the same auditory cortex, which were conducted on different days, was highly reproducible. Furthermore, other auditory fields surrounding AI in the recorded area were allocated based on the observed tonotopicity. We also conducted unit recordings on the cats used for optical recording with the same set of acoustic stimuli. The gross feature of the arrangement of optimal frequencies determined by unit recordings agreed with the tonotopic arrangement determined by the optical recording, although the precise agreement was not obtained.

Acoustic Stimulation↗

Self-organization model of cytochrome oxidase blobs and ocular dominance columns in the primary visual cortex.

There are regularly arranged blobs that contain neurons labeled by cytochrome oxidase (CO) in the supragranular layer of the primary visual cortex (V1) of monkeys and cats. This theoretical study demonstrates that CO-blob-like patterns can be reproduced based on the thermodynamic model for the activity-dependent self-organization of afferent inputs from two different groups of neurons to the supragranular layer of the visual cortex. Computer simulation based on the model shows that within a particular parameter range each blob is centered in the ocular dominance (OD) band, as observed in macaque monkeys and galagos. Furthermore, by increasing the strength of correlation in activity between inputs from the two eyes, nearby blobs merge across OD borders, as seen in the cat visual cortex. Finally, for monocular deprivation, blobs in the deprived eyes shrink as observed in monkeys and cats. For binocular deprivation, less intensely labeled blobs were reproduced, while the blob density did not change as observed in monkeys.

Algorithms↗

Amelioration of hippocampal neuronal damage after transient forebrain ischemia in cyclooxygenase-2-deficient mice.

Several studies have suggested that cyclooxygenase-2 (COX-2) plays a role in ischemic neuronal death. Genetic disruption of COX-2 has been shown to reduce susceptibility to focal ischemic injury and N-methyl-d-aspartate-mediated neurotoxicity. The purpose of this study was to examine the effects of COX-2 deficiency on neuronal vulnerability after transient forebrain ischemia. Marked upregulation of COX-2 immunostaining in neurons was observed at the early stage and prominent COX-2 staining persisted in the CA1 medial sector and CA2 sector over 3 days after ischemia. The immunohistologic pattern of COX-2 staining in these sectors gradually condensed to a perinuclear location. The degree of hippocampal neuronal injury produced by global ischemia in COX-2-deficient mice was less than that in wild-type mice, coincident with attenuation of DNA fragmentation in the hippocampus. Also, treatment with a selective COX-2 inhibitor, nimesulide, after ischemia decreased hippocampal neuronal damages. These results of genetic disruption and chemical inhibition of cyclooxygenase-2 show that inhibition of COX-2 ameliorates selective neuronal death after transient forebrain ischemia in mice.

Animals↗

[Evaluation of quantitative fit-testing of N95 filtering facepiece respirators using Mask-Fitting Tester and improvement of mask fitting by instruction].

OBJECTIVE: To evaluate quantitative fitness of N95 filtering facepiece respirators (N95 Mask) using Mask Fitting Tester and improvement of fitness by instruction. MATERIALS AND METHODS: One hundred and thirty-three health care workers working at our hospital were tested as to quantitative fitness of N95 Mask using Mask Fitting Tester Model MT-02, Roken type that counts particles more than 0.7 microm in diameter. Based on counting the number of particles more than 0.7 microm in diameter of the air inside and outside the mask, leakage rate is calculated. Permissible range of leakage rate is 10% or below. In case of leakage rate more than 10%, we instructed way of wearing N95 Mask or change a type of N95 Mask. We usually provide three types of N95 Mask. RESULTS: Eighty-seven (65.4%) out of 133 health care workers achieved leakage rate 10% or below at the first test. Forty-six (34.6%) who did not achieve leakage rate 10% or below at the first test received instruction or changed a mask type. Twenty-one (15.8%) achieved desired value by instruction and 19 (14.3%) by changing a mask type. But 6 (4.5 %) could not achieve desired value in spite of instruction or changing to another type of masks available to us. Leakage rate changed from 20.5 +/- 10.9% (10.1-58.6) to 6.3 +/- 4.9% (0-29.5) by instruction or changing a type of mask (p < 0.001). At the first test, mask fitness is better in male than female, and worse in workers who always use N95 Mask at isolation ward or laboratory room than workers who usually do not use N95 Mask. Main problems were choice of mask, fitness to nose, incorrect use of headband. CONCLUSION: It is useful to evaluate N95 Mask quantitative fitness using Mask Fitting Tester Model MT-02, Roken type. At the first test, 34.6% of health care workers have large amount of leakage more than 10%, and by instruction or changing a mask type, most of them could achieve 10% or below. But 4.5% could not achieve desired value. On Infection control, it is important to test quantitative fitness of N95 Mask and to provide more than three types of N95 Mask.

Equipment Design↗

Effect of a single injection of humanized anti-CD154 monoclonal antibody on the platelet-specific autoimmune response in patients with immune thrombocytopenic purpura.

Blockade of the CD40/CD154 signal is a potential immunomodulatory strategy for T-cell-mediated diseases. As a part of a phase 1, multicenter, dose-escalating trial of humanized monoclonal antibody to CD154 (IDEC-131/E6040) in patients with refractory immune thrombocytopenic purpura (ITP), the autoimmune response to glycoprotein IIb/IIIa (GPIIb/IIIa) was evaluated at successive time points. Five patients each were given a single infusion of 1, 2, 5, or 10 mg/kg IDEC-131/E6040 and followed for 3 months. All adverse events were mild, and there were no severe infections or thromboembolic events. No increase in platelet count was observed in patients treated at 1, 2, or 5 mg/kg, but an increase was observed in 3 patients treated at 10 mg/kg. In only the patients treated at 5 or 10 mg/kg, the frequency of B cells producing anti-GPIIb/IIIa antibodies, GPIIb/IIIa-induced T-cell proliferation, and anti-GPIIb/IIIa antibody production by antigen-dependent T-B-cell collaboration were all suppressed in parallel after the treatment, with a slow return to baseline. In contrast, T-cell response to an irrelevant antigen was not affected. These findings suggest that CD40/CD154 blockade therapy is potentially effective for refractory ITP, through selective suppression of autoreactive T and B cells to platelet antigens.

Adult↗

Implication of cyclooxygenase-2 on enhanced proliferation of neural progenitor cells in the adult mouse hippocampus after ischemia.

Global ischemia promotes neurogenesis in the dentate gyrus of the adult mouse hippocampus. Cyclooxygenase (COX)-2, the principal isoenzyme in the brain, modulates inflammation, glutamate-mediated cytotoxicity, and synaptic plasticity. We demonstrated that delayed treatment with different classes of COX inhibitor significantly blunted enhancement of dentate gyrus proliferation of neural progenitor cells after ischemia. COX-2 immunoreactivity was observed in both neurons and astrocytes in the dentate gyrus, but not in neural progenitor cells in the subgranular zone. Moreover, in the postischemic dentate gyrus of heterozygous and homozygous COX-2 knockout mice, proliferating bromodeoxyuridine-positive cells were significantly fewer than in wild-type littermates. These results demonstrate that COX-2 is an important modulator in enhancement of proliferation of neural progenitor cells after ischemia.

Animals↗

Functional organization of the cat visual cortex in relation to the representation of a uniform surface.

Neuronal activity in the early visual cortex has been extensively studied from the standpoint of contour representation. On the other hand, representation of the interior of a surface surrounded by a contour is much less well understood. Several studies have identified neurons activated by a uniform surface covering their receptive fields, but their distribution within the cortex is not yet known. The aim of the present study was to obtain a better understanding of the distribution of such neurons in the visual cortex. Using optical imaging of intrinsic signals, we found that there are a group of surface-responsive regions located in area 18, along the area 17/18 border, that tend to overlap the singular points of the orientation-preference map. Extracellular recordings confirmed that neurons responsive to uniform plane stimuli are accumulated in these regions. Such neurons also existed outside the surface-responsive regions around the singular points. These results suggest that there exists a functional organization related to the representation of a uniform surface in the early visual cortex.

Animals↗

Lack of relationship between occupational exposure to carbon disulfide and endocrine dysfunction: a six-year cohort study of the Japanese rayon workers.

OBJECTIVES: A six-year prospective cohort study was conducted to clarify whether the current carbon disulfide (CS2) exposure level is low enough to prevent subclinical health impairment and/or to ameliorate health effects due to previous high exposure. This paper describes the follow-up results, exposure assessment, and effects on the endocrine system. METHODS: The study subjects were 432 male workers exposed to CS2 at one of the 11 rayon factories in Japan and 402 referent workers from the same factories, all of whom were examined in 1992-93. 251 CS2-exposed, 140 former-exposed and 359 referent workers participated in the follow-up survey (follow-up rate 89.9%) in 1998-99. Urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) at the end of a shift as internal exposure index and the time-weighted average CS2 concentration as external exposure index were measured twice a year from 1992-1993. By using various blood indices, we evaluated effects on thyroid, hypophysis, and gonad function, as well as effects on glucose metabolism. Information on potential confounding factors, such as age, smoking and alcohol drinking, were collected and adjusted for. RESULTS: When the individual exposure level was represented by arithmetic mean for TTCA and CS2 concentration, geometric means (SD) of CS2 workers were 1.61 (1.91) mg/g.crea and 5.02 (1.84) ppm, respectively. There were no exposure-related differences in glucose metabolism or any of the endocrinological indices. CONCLUSIONS: No biologically significant effects of CS2 were found on endocrine function in Japanese rayon manufacturing workers when the average internal and external exposure levels were maintained below the current occupational exposure limit.

Adult↗

Differential Akt phosphorylation at Ser473 and Thr308 in cultured neurons after exposure to glutamate in rats.

Akt kinase is involved in growth factor-mediated neuronal protection. In the present study, we found in cultured neurons exposed to glutamate, that phosphorylation at Ser473 was transiently induced, but the level of phosphorylation at Thr308 and Akt activity were unchanged. Inhibition of phosphoinositide 3-kinase with LY294002 decreased phosphorylation and Akt activity, however, pretreatment with LY294002 did not affect glutamate toxicity. Our findings suggested that the endogenous Akt pathway does not play a crucial role in cell survival after exposure to glutamate.

Animals↗