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Biomedical subjects

E Shimizu

Publications and source records attributed to E Shimizu.

At least 19 recordsLinked to original sources

Effects of electrical stimulation of the raphe area on the micturition reflex in cats.

The raphe nucleus has a variety of physiological functions, including emotion, regulation of skeletal muscle motoneurons, spinal transmission of nociceptive signals, sleep, respiration, gastric motility, and cardiovascular function. Recent evidence has shown that centrally administered serotonin has modulatory effects on micturition function, and that decreased brain serotonin might underlie depression and an overactive bladder. We applied high-frequency stimulation (HFS; 0.2-ms duration, 100 Hz) in the raphe nucleus and the adjacent midline area in 20 supracollicular decerebrate cats, which mostly elicited inhibition of the micturition reflex. The effective amplitude of the electrical stimulation for evoking inhibitory responses was less than 50 muA. We also examined single neuronal activities in the raphe nucleus in response to isovolumetric spontaneous micturition reflexes. In total, 79 neurons were recorded in the raphe nucleus that were related to urinary storage/micturition cycles. Of the neurons recorded, the most common were tonic storage neurons (48%), followed by tonic micturition neurons (28%), phasic storage neurons (18%), and phasic micturition neurons (6%). In addition to the tonic/phasic as well as storage/micturition classification, the neurons showed diverse discharge patterns: augmenting, constant and decrementing, with the constant discharge pattern being most common. Among neurons in the raphe nucleus, the neurons with a decrementing discharge pattern were concentrated in the rostral portion, whereas the augmenting and constant neurons existed diffusely. The storage and micturition neurons were intermingled in the rostral portion, whereas they were separate in the caudal portion. In conclusion, the results of the present study indicate that HFS of the raphe area inhibits the micturition reflex and that there are micturition-related neuronal firings in the raphe area in cats, suggesting that the raphe nucleus is involved in neural control of micturition.

Action Potentials↗

Coffee consumption and glucose tolerance status in middle-aged Japanese men.

AIMS/HYPOTHESIS: Several studies have reported that coffee has a protective effect against the development of type 2 diabetes. However, few of these studies used the standard glucose tolerance test to diagnose type 2 diabetes. The aim of this study was to investigate the relationship between coffee and green tea consumption and glucose tolerance status as determined using a 75-g OGTT. METHODS: We performed a cross-sectional study of 3224 male officials of the self-defence forces. Glucose tolerance status was determined in accordance with the 1998 World Health Organization criteria, and average intakes of coffee and green tea over the previous year were assessed by a self-administered questionnaire. The figures obtained were adjusted for BMI, physical activity and other factors. RESULTS: A total of 1130 men were identified as having glucose intolerance (IFG, IGT or type 2 diabetes). Compared with those who did not consume coffee on a daily basis, fasting and 2-h post-load plasma glucose levels were 1.5% and 4.3% lower in those who drank 5 cups of coffee or more per day respectively. The adjusted odds ratios of glucose intolerance for categories of <1, 1-2, 3-4 and >/=5 cups of coffee per day were 1.0 (referent), 0.8 (95% CI 0.6-1.0), 0.7 (95% CI 0.6-0.9) and 0.7 (95% CI 0.5-0.9) respectively (p=0.0001 for trend). No clear association was observed between green tea drinking and glucose tolerance status. CONCLUSIONS/INTERPRETATION: Coffee consumption may inhibit postprandial hyperglycaemia and thereby protect against the development of type 2 diabetes mellitus.

Alcohol Drinking↗

Development and progression of diabetic retinopathy in patients with Type 1 diabetes who are positive for GAD autoantibody.

AIMS: To investigate the relationship between autoantibodies to glutamic acid decarboxylase (GAD) and proliferative diabetic retinopathy (PDR) to assess the role of autoimmunity in retinopathy. METHODS: Patients with Type 1 diabetes for more than 10 years who had been diagnosed under age 30 (13-28 years) were studied. They were classified into three groups. The PDR group consisted of 22 patients, the pre-PDR group was 26 patients, while the non-DR group was 32 patients who had Type 1 diabetes without retinopathy. Blood was collected to measure autoantibodies to GAD, and the relationship between PDR and GAD positivity was investigated in a cross-sectional study. RESULTS: The highest positivity rate of GAD autoantibodies was 50.0% in the non-DR group, followed by the pre-PDR group (30.8%) and the PDR group (18.2%). CONCLUSIONS: Production or existence of GAD autoantibodies may contribute to the prevention of retinopathy.

Adolescent↗

A short daytime test using correlation dimension for respiratory movement in OSAHS.

In order to examine the pathology in patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS), the nonlinear properties of respiratory movement and breath-to-breath variations during resting wakefulness with eyes closed was investigated. Recording of the respiratory movement using inductive plethysmography was performed on 14 patients with OSAHS and 13 control subjects for 2 h in the supine position during daytime. To calculate the correlation dimension (D2) for respiratory movement, an algorithm proposed by Grassberger and Procaccia was applied. The indices of breath-to-breath variations were estimated. To calculate D2 and breath-to-breath variations, two different segments were selected (200 s each). The value of D2 for respiratory movement in patients with OSAHS was significantly greater than that in control subjects. In the case of > or = 2.0 of D2 for respiratory movement, the sensitivity and specificity of detecting the presence of OSAHS was 85.7% and 76.9%, respectively. On the basis of breath-to-breath variations, only the coefficient of variation of expiratory time for respiratory movement in patients with OSAHS was significantly greater than that in the control subjects. In conclusion, the measurements of correlation dimensions for respiratory movement with a brief period during wakefulness may be a useful index for identifying patients with obstructive sleep apnoea/hypopnoea syndrome.

Adult↗

Measuring subepithelial thickness using endobronchial ultrasonography in a patient with asthma: a case report.

The chronic inflammation of bronchial asthma is characterized by swelling of the subepithelial mucosa. However, it is difficult to assess subepithelial edema clinically. We report the case of a patient with asthma whose subepithelial edema was evaluated by endobronchial ultrasonography. Receiving montelukast 10 mg/day for 2 weeks, a 42-year-old man with mild, persistent asthma had his symptoms controlled by beta2-inhalation alone. Pretreatment endobronchial ultrasonography revealed subepithelial thickening in the right main stem bronchus, with a low absorption area suggestive of edema. Two weeks of montelukast therapy diminished the amount of subepithelial edema. Endobronchial ultrasonography is a promising technique for determining subepithelial edema in the asthmatic airway.

Adult↗

Dynamic changes in AP-1 transcription factor DNA binding activity in rat brain following administration of antidepressant amitriptyline and brain-derived neurotrophic factor.

The present study was undertaken to examine the effects of the antidepressant, amitriptyline, and brain-derived neurotrophic factor (BDNF) on activator protein-1 (AP-1) DNA binding activity in the rat brain. Acute administration of amitriptyline (5 or 10 mg/kg) initially increased but then decreased AP-1 DNA binding activity in the rat frontal cortex and hippocampus. Chronic administration of amitriptyline (5 or 10 mg/kg, once daily for 3 weeks) initially decreased AP-1 DNA binding activity but ultimately resulted in its persistent elevation in the rat frontal cortex. In contrast, the chronic administration of amitriptyline did not affect the low activity of AP-1 DNA binding in the hippocampus. However, chronic administration of amitriptyline (10 mg/kg, once daily for 3 weeks) significantly increased BDNF protein levels in the hippocampus (by 26.9%) and frontal cortex (by 24.6%). Direct infusion of BDNF (1 microg) into the hippocampal dentate gyrus significantly increased hippocampal AP-1 DNA binding activity. These results suggest that AP-1 transcription factor may be modulated by BDNF and that it may be an important target for the action of antidepressants.

Amitriptyline↗

Fibrinogens Kosai and Ogasa: Bbeta15Gly-->Cys (GGT-->TGT) substitution associated with impairment of fibrinopeptide B release and lateral aggregation.

We found two heterozygous dysfibrinogenemias, designated fibrinogen Kosai and fibrinogen Ogasa. Kosai was associated with arteriosclerosis obliterans but Ogasa showed no bleeding or thrombotic tendencies. The plasma fibrinogen concentrations from the two propositi (Ogasa and Kosai) were much lower when determined by the thrombin-time method (0.94 and 1.06 g L(-1), respectively) than when determined by the immunological method (2.87 and 2.72 g L(-1), respectively). We performed DNA sequencing and functional analyses to clarify the relationship between the structural and functional abnormalities. Genetic analysis of PCR-amplified DNA from the propositi identified the heterozygous substitution Bbeta15Gly-->Cys (GGT-->TGT). Western blotting analysis of purified fibrinogen revealed the existence of albumin-fibrinogen complexes. Functional analyses indicated that compared with the normal control, the propositi's fibrinogen released only half the normal amount of fibrinopeptide B and showed markedly impaired polymerization. In addition, the observation of thinner fibers in fibrin clots (by scanning electron microscopy) indicated markedly defective lateral aggregation in the variant fibrinogens. The impaired functions may be due to the substitution of Cys for Bbetao15Gly plus the existence of some additional disulfide-bonded forms.

Adult↗

Genome-wide gene expression profiles of the developing mouse hippocampus.

We have analyzed the developmental molecular programs of the mouse hippocampus, a cortical structure critical for learning and memory, by means of large-scale DNA microarray techniques. Of 11,000 genes and expressed sequence tags examined, 1,926 showed dynamic changes during hippocampal development from embryonic day 16 to postnatal day 30. Gene-cluster analysis was used to group these genes into 16 distinct clusters with striking patterns that appear to correlate with major developmental hallmarks and cellular events. These include genes involved in neuronal proliferation, differentiation, and synapse formation. A complete list of the transcriptional changes has been compiled into a comprehensive gene profile database (http://BrainGenomics.Princeton.edu), which should prove valuable in advancing our understanding of the molecular and genetic programs underlying both the development and the functions of the mammalian brain.

Animals↗

Extrathymic development of V alpha 11 T cells in placenta during pregnancy and their possible physiological role.

The molecular and cellular mechanisms of the feto-maternal immune responses in the placenta in connection with natural abortion remain unclear. In this report we provide evidence that V(alpha11) T cells developed in the placenta may be responsible for the induction of natural abortion. The majority of V(alpha11) TCRs detected during pregnancy showed a consensus motif in the CDR3 region, similar to that of anti-GM3 TCR clones, and were of maternal origin. V(alpha11) TCRs were found in the middle to late stages of gestation due to de novo generation in the placenta, not to migration from the maternal side, as evidenced by the significant increases in the out-of-frame V(alpha11) TCR mRNA and the copy number of circular DNA generated by V(alpha11) gene rearrangements. Furthermore, administration of anti-V(alpha11) Ab to pregnant mice resulted in a significant decrease in the incidence of fetal demise, suggesting that V(alpha11) T cells detected in the placenta develop extrathymically and are involved in natural abortion.

Animals↗

Purification and characterization of aminopropionaldehyde dehydrogenase from Arthrobacter sp. TMP-1.

Aminopropionaldehyde dehydrogenase was purified to apparent homogeneity from 1,3-diaminopropane-grown cells of Arthrobacter sp. TMP-1. The native molecular mass and the subunit molecular mass of the enzyme were approximately 20,5000 and 52,000, respectively, suggesting that the enzyme is a tetramer of identical subunits. The apparent Michaelis constant (K(m)) for 1,3-diaminopropane was approximately 3 microM. The enzyme equally used both NAD(+) and NADP(+) as coenzymes. The apparent K(m) values for NAD(+) and NADP(+) were 255 microM and 108 microM, respectively. The maximum reaction rates (V(max)) for NAD(+) and NADP(+) were 102 and 83.3 micromol min(-1) mg(-1), respectively. Some tested aliphatic aldehydes and aromatic aldehydes were inert as substrates. The optimum pH was 8.0-8.5. The enzyme was sensitive to sulfhydryl group-modifying reagents.

Aldehyde Oxidoreductases↗

Inhibition of tumor metastasis by adoptive transfer of IL-12-activated Valpha14 NKT cells.

A unique lymphocyte lineage, the Valpha14 NKT cells, expresses both NK1.1 and an invariant antigen receptor encoded by Valpha14 and Jalpha281 gene segments. Valpha14 NKT cells play crucial roles in various immune responses, including autoimmune diseases, allergic reactions and anti-tumor immunity. Valpha14 NKT cells were demonstrated to be essential for anti-tumor effect of IL-12 in vivo. Here, we report that adoptive transfer of IL-12-activated Valpha14 NKT cells prevents hepatic metastasis of B16 melanoma. The injection of large amounts of IL-2, IL-4, and IFN-gamma, which are cytokines produced by activated Valpha14 NKT cells, exhibited no significant inhibition of the metastasis of this melanoma. The cells prepared from the liver of IL-12-injected mice expressed a potent cytotoxic activity on B16 melanoma cells in vitro. Although the adoptive transfer of IL-12-activated Valpha14 NKT cells prevents hepatic metastasis of B16 melanoma, activated NK cells from IL-12-injected RAG-1-/- mice failed to inhibit the metastasis of this melanoma. Thus, the anti-tumor effect of IL-12 can be replaced by adoptive transfer of IL-12-activated Valpha14 NKT cells but not by IL-12-activated NK cells, suggesting a minor role of NK cells for the IL-12-mediated anti-tumor effect in this experimental system. Moreover, our studies have suggested the involvement of direct cytotoxic mechanisms rather than cytokine-mediated immune responses at the effector phase of the Valpha14 NKT cell-mediated anti-tumor activity.

Adoptive Transfer↗

Stretch induces a growth factor in alveolar cells via protein kinase.

Positive-pressure mechanical ventilation can injure the lung, causing edema and alveolar inflammation in a complication termed ventilator-induced lung injury (VILI). Cytokines such as interleukin-8 (IL-8) reportedly are important in this inflammatory response. On the other hand, hepatocyte growth factor (HGF) promotes regeneration of the lung, and delays pulmonary fibrosis. We postulated that cyclic stretch upregulates production and release of both of mediators. Human alveolar epithelial cells (A549) cultured on a silicoelastic membrane were tested for mRNA expression and release of IL-8 and HGF after cyclic stretch in vitro. Stretch induced mRNA expression and release of these mediators. The signaling pathway from cyclic stretch to release of IL-8 and HGF appeared to involve protein kinase C in the signal transduction pathway.

Cells, Cultured↗

Theophylline chronotherapy of nocturnal asthma using bathyphase of circadian rhythm in peak expiratory flow rate.

We studied the efficacy of theophylline chronotherapy for nocturnal asthma using the changes of the circadian rhythms in peak expiratory flow rate (PEF). Eight patients with nocturnal asthma were evaluated for the periods with nocturnal symptoms and with an evening dose of theophylline administered daily. Patients recorded their PEF every 4 hours on one of the days (from 7:00 to 23:00 h) in each period. Circadian rhythms in PEF were examined using the single and group-mean cosinor method. Significant circadian rhythms in PEF were observed in the period with nocturnal symptoms. When nocturnal symptoms were present, the bathyphase of PEF was present between midnight and morning. A significant circadian rhythm disappeared or PEF amplitude decreased during theophylline chronotherapy. The circadian rhythm in PEF was altered according to the severity of the asthma. In patients with symptoms present between midnight and early morning, an evening dose of theophylline chronotherapy can be prophylactically used for nocturnal asthma attacks. Consideration of the circadian rhythm and bathyphase of PEF is useful in selecting appropriate chronotherapy for nocturnal asthma.

Adult↗

Nonlinear behavior of human respiratory movement during different sleep stages.

To investigate the nonlinear properties of respiratory movement during different sleep stages, we applied an algorithm proposed by Grassberger and Procaccia to calculate the correlation dimension in rapid eye movement and non-rapid eye movement sleep. We also tested for nonlinearity in respiratory movement by comparing the correlation dimension for the original data with that for surrogate data. The study population included eight healthy volunteers. We recorded respiratory movement and the sleep electroencephalogram for 8 h. The correlation dimension for respiratory movement was 3.28+/-0.19 (mean +/- SD) during rapid eye movement sleep, 2.31+/-0.21 during light sleep (stage I) and 1.64+/-0.25 during deep slow-wave sleep (stage IV). Thus, the correlation dimension differed significantly by sleep stage (p < 0.001): it was least during stage IV sleep and greatest during REM. The correlation dimension for the original data also differed from that for surrogate data, confirming nonlinearity in original data. The results suggest that the nonlinear dynamics of respiratory movement in sleep changes with sleep stage, presumably due to the information processing by the cerebral cortex. The increased correlation dimension for respiratory movement in REM sleep may be related to increased cortical information processing associated with dreaming.

Adult↗