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N Yoshimura

Publications and source records attributed to N Yoshimura.

At least 271 records · Page 15Linked to original sources
PubMed1996

Different types of Na+ and A-type K+ currents in dorsal root ganglion neurones innervating the rat urinary bladder.

1. Whole-cell patch-clamp recording in combination with axonal tracing techniques was used to examine the electrical properties of afferent neurones innervating the urinary bladder of the adult rat. Individual bladder afferent cells were labelled by Fast Blue (FB), injected into the bladder wall. 2. Passive and active electrical parameters at room temperature (20-22 degrees C) in FB-labelled bladder afferent neurones were comparable with those in unlabelled neurones. Unselected dorsal root ganglion (DRG) neurones as well as bladder afferent neurones exhibited two different types of action potential: high-threshold humped spikes in small-sized neurones and low-threshold narrow spikes in large-sized neurones. 3. The majority (70%) of bladder neurones which were small in size expressed high-threshold tetrodotoxin (TTX)-resistant Na+ channels and slow-inactivating A-type K+ channels (KA), which were available at the resting membrane potential, whereas large-sized DRG neurones had low-threshold TTX-sensitive Na+ channels and fast-inactivating KA channels, which were almost completely inactivated at the resting membrane potential. 4. Half-maximal conductances of activation of TTX-resistant and TTX-sensitive Na+ currents were obtained at -10.3 and -25.3 mV, respectively. The TTX-resistant and TTX-sensitive Na+ currents were half-inactivated at -25.3 and -56 mV, respectively. 5. In the TTX-resistant neurones, the transient outward K+ current (A-type current, IA) with half-maximal conductance at -40.8 mV was half-inactivated at -77.5 mV, and exhibited slower decaying kinetics (mean decay constant (tau), 240 ms) than the IA current recorded from the large-sized TTX-sensitive neurones (mean tau, 20 ms). 6. These results suggest that the majority of bladder afferent neurones have high electrical thresholds for spike activation due to the TTX-resistant Na+ current and the slow-inactivating IA current, which reflect the large population of unmyelinated high-threshold C fibre afferents that innervate the urinary bladder.

Action Potentials↗
PubMed1996

Spinal antinociceptive effect of substance P on the responses induced by intrathecally injected NMDA in mice.

Substance P (SP) has previously been shown to be involved in the transmission of nociceptive information in the spinal dorsal horn. In this study we investigated whether a functional interaction exists between SP and excitatory amino acids in the spinal cord of mice. Behavioral responses were observed after intrathecal co-administration of SP and N-methyl-D-aspartate (NMDA). The high dose (12 pmol) of SP potentiated NMDA (0.25 nmol)-induced behavior consisted of caudally directed licking and biting, while the low dose (1 pmol) of SP significantly reduced this behavior. This inhibitory effect of low dose of SP was blocked by intrathecal co-administration of opioid receptor antagonist naloxone (4 nmol). These results suggest that SP is also involved in the antinociception which is dependent on opioid mechanisms at the spinal level.

Animals↗
PubMed1996

Inducible nitric oxide synthase in retinal ischemia-reperfusion injury.

The purpose of this study was to determine whether inducible nitric oxide synthase (iNOS) was implicated in the pathogenesis of retinal ischemia-reperfusion injury. Semi-quantitative reverse transcription-polymerase chain reaction showed that the level of iNOS mRNA expression was markedly increased in rat retina following transient ischemia, with peak expression at 12 hr after reperfusion (15.7-fold increase over pre-ischemic levels). In situ hybridization showed that iNOS mRNA was expressed by resident retinal cells, most likely glial cells in the innermost retina, and also by the neutrophils that had infiltrated the retina. Intraperitoneal administration of NG-(1-iminoethyl)-L-ornithine (L-NIO), an inhibitor of iNOS, significantly increased the rate of b-wave recovery compared to that of control animals. The values (mean +/- S.E.M.) were 55.0 +/- 4.4% versus 40.1 +/- 5.1% (P < 0.05) at 1 day and 68.6 +/- 6.6% versus 45.8 +/- 3.5% (P < 0.05) at 3 days. This study shows that iNOS mRNA is highly expressed by non-neuronal cells of the inner retina during reperfusion following transient retinal ischemia. It also shows that L-NIO treatment provides some protection against ischemia-reperfusion injury. We suggest that nitric oxide produced by iNOS may mediate retinal ischemia-reperfusion injury.

Animals↗
PubMed1996

Nasal biopsy in the early diagnosis of Wegener's (pathergic) granulomatosis. Significance of palisading granuloma and leukocytoclastic vasculitis.

The diagnostic value of the nasal biopsy in the early diagnosis of Wegener's granulomatosis and its value in prognosis were examined in 11 patients with a clinicopathological diagnosis of the disease. The vascular lesions found included microabscess in the vascular walls in 82%, leukocytoclastic capillaritis in 73%, fibrinoid necrosis of blood vessels in 45%, leukocytoclastic endovasculitis in 27%, and palisading granuloma in vascular wall in 9% of cases. The extravascular lesions included palisading granuloma in all cases, microabscess in 91%, and diffuse granulomatous tissues in 82%. Palisading microgranuloma (82%) was more frequent than palisading macrogranuloma (45%). After therapy, complete remission occurred in 8 patients, but 3 patients died of sepsis, diffuse pulmonary haemorrhage, and cerebral haemorrhage. Comparison of the frequency of each finding in the nasal biopsy specimens between patients who achieved remission and those who died showed that leukocytoclastic vasculitis was found more commonly in fatal cases, and leukocytoclastic endovasculitis was observed only in fatal cases. Palisading granuloma as a vascular or extravascular lesion is the primary and most important finding in a histopathological diagnosis of Wegener's granulomatosis, microabscess in vascular walls is a secondary but the next most important finding, and leukocytoclastic vasculitis heralds dissemination of the disease and poor prognosis. It requires aggressive therapy.

Adult↗
PubMed1996

Ectopic accumulation of 99mTc-HMDP in primary lung cancer in comparison with CT findings.

The purpose of this study was to evaluate the frequency and the extent of extraosseous 99mTc-HMDP accumulation in 412 patients with primary lung cancer. CT scanning was also performed and we compared the extraosseous uptake by lung cancer with the internal structure of the tumor on CT scans. The extent of ectopic 99mTc-HMDP accumulation was classified as low, moderate or high. CT scans were used to evaluate the size and internal structure of the tumor, including calcification and necrosis. Ectopic 99mTc-HMDP accumulation in primary lung cancer was found in 32 patients (7.7%), and included 2 cases (0.5%) of high uptake, 8 cases (1.9%) of moderate uptake, and 22 cases (5%) of low uptake. No difference in uptake was observed among the histological types, but a relationship between tumor size and 99mTc-HMDP extraosseous accumulation was observed. CT scans of the 32 tumors exhibiting ectopic 99mTc-HMDP accumulation revealed 5 cases of calcification in the tumor and 18 cases of tumor necrosis. The factors promoting ectopic 99mTc-HMDP accumulation were considered to be tumor size and calcification or necrotic change. In patients with neither calcification nor necrosis, other factors such as increased calcium metabolism and altered vascular permeability may be involved.

Adenocarcinoma↗
PubMed1996

Staged repair of tetralogy of Fallot and pulmonary atresia without central pulmonary arteries.

A 15-year-old boy with tetralogy of Fallot and pulmonary atresia without central pulmonary arteries who was successfully treated using a staged approach is presented. The first stage consisted of the creation of central pulmonary arteries. In the second stage, the continuity between the right ventricle and the pulmonary arteries was established with closure of the ventricular septal defect. Some patients previously considered to be unsuitable candidates for correction may be successfully repaired using this approach.

Adolescent↗
PubMed1996

Methylprednisolone inhibits endotoxin-induced depression of contractile function in human arteries in vitro.

We have studied the effect of methylprednisolone on endotoxin-induced depression of contractile function in human gastroepiploic arteries. Endotoxin diminished the contractile response to noradrenaline in both the presence and absence of endothelium. This attenuation began after 4 h and reached a maximum after 10 h of endotoxin exposure. The cGMP content of endotoxin-treated rings was approximately seven-fold higher than in control rings. These endotoxin-mediated responses were blocked by L-NAME and methylene blue. These data indicate that the main cause of vascular hyposensitivity to noradrenaline was massive generation of nitric oxide. Pretreatment with methyl-prednisolone at concentrations (2.0-20.0 micrograms ml-1) similar to those achieved in plasma after therapeutic administration dose-dependently inhibited these endotoxin-mediated responses. These data support the concept that pharmacological administration of methylprednisolone has the potential to prevent endotoxin-induced depression of the contractile response to noradrenaline seen in endotoxaemic shock.

Acetylcholine↗
PubMed1996

Lipoteichoic acid from Staphylococcus aureus depresses contractile function of human arteries in vitro due to the induction of nitric oxide synthase.

The aim of this study was to clarify the role of Gram-positive organisms in the genesis of sepsis. In the present study, we investigated the effect of lipoteichoic acid (LTA) from the cell wall of Staphylococcus aureus on contractions elicited by norepinephrine (NE) in rings cut from human gastroepiploic arteries. LTA diminished the contractile response to NE. This attenuation began after several hours of exposure, whether or not endothelium was present. The cyclic guanosine monophosphate content of LTA-treated rings was higher than that of control rings, whether there was a functional endothelium. These LTA-mediated responses were reduced significantly by inhibitors of nitric oxide (NO) synthase and guanylate cyclase. All of this indicates that the main underlying cause of the vascular hyporeactivity to NE was a massive generation of No. In addition, cycloheximide, an inhibitor of inducible NO synthase, prevented the attenuation of NE-induced contractions caused by LTA. Thus, our results offer strong supporting evidence that the important factor in the genesis by Gram-positive organisms of a diminished contractile response to pressor drugs is their induction of inducible NO synthase in smooth muscle.

Abdominal Muscles↗
PubMed1996

Does the redox state of cytochrome aa3 reflect brain energy level during hypoxia? Simultaneous measurements by near infrared spectrophotometry and 31P nuclear magnetic resonance spectroscopy.

We studied cerebral oxygen metabolism during hypoxia to demonstrate whether the redox state of cytochrome aa3 (cyt.aa3), as measured by near infrared spectrophotometry (NIRS), reflects brain energy level. Rats (n = 6) subjected to hypoxia were simultaneously monitored by NIRS and 31P nuclear magnetic resonance spectroscopy (NMRS). Brain function was evaluated using the electroencephalogram (EEG). After a reduction of the fraction of inspired oxygen FIO2 from 0.21 to 0.15, we observed a significant increase in reduced cyt.aa3 (from 16.5% +/- 2.1% to 41.2% +/- 2.8%; P < 0.01), without significant changes in phosphocreatine (PCr) and beta-adenosine triphosphate (beta-ATP) levels. The PCr decreased significantly at a FIO2 of 0.10 (53.8% +/- 6.4% as compared with 97.7% +/- 10.9% at a FIO2 of 0.21; P < 0.05), and reached a minimum at a FIO2 of 0.04. beta-ATP did not change significantly at a FIO2 of 0.10 or 0.08. With a FIO2 of less than 0.08, cyt.aa3 was almost totally reduced. EEG activity slowed at a FIO2 of 0.08 and became isoelectric at 0.04. Significant correlations were found between the levels of cyt.aa3 and PCr (P < 0.001, r = 0.83) as well as between cyt.aa3 and beta-ATP (P < 0.001, r = 0.73) by using the overall values at FIO2 levels from 0 to 1.0. However, no significant correlations were observed among these variables when the FIO2 was less than 0.10. These findings suggest that the increase in reduced cyt.aa3 reflects brain energy depletion; however, the redox state of cyt.aa3 will not indicate brain energy depletion during extreme hypoxia because cyt.aa3 is reduced totally during hypoxia insufficient to deplete intracellular ATP.

Adenosine Triphosphate↗
PubMed1996

Nitric oxide as a mediator of reduced arterial responsiveness in septic patients.

OBJECTIVE: To investigate the functional status of arteries in patients with septic shock, each of whom suffered from severe hypotension. DESIGN: Experimental, comparative study. SETTING: Laboratory in a university hospital. SUBJECTS: Mesenteric artery resected from omentum was obtained from patients (n = 3) with or without (n = 4) sepsis. INTERVENTIONS: To study the effect of modification of the nitric oxide system in human arteries during sepsis, changes in norepinephrine-evoked isometric tension in mesenteric arterial rings were measured. MEASUREMENTS AND MAIN RESULTS: Mesenteric arteries were isolated from omentum resected from three patients with septic shock and from four patients with no inflammatory conditions; in each case, during an intestinal anastomosis. In arterial rings, after a 1-hr equilibration with Krebs solution, changes in isometric tension evoked by norepinephrine were measured for 5 mins every 20 mins. The tension initially evoked in rings from septic patients was lower than in those rings from nonseptic patients and, unlike the controls, it decreased with a short time course. The addition of 300 micromol/L of N(G)-nitro-L-arginine methyl ester or 10 micromol of N(G)-nitro-L-arginine methyl ester or 10 micromol/L of methylene blue reversed this decrease. CONCLUSION: These results indicate that in patients with septic shock, the main cause of reduced sensitivity to pressor agents may be a massive generation of nitric oxide via the L-arginine pathway.

Aged↗
PubMed1996

Differential respiratory activity of four abdominal muscles in humans.

Together the abdominal muscles contribute significantly to ventilation under some conditions, but there is little information regarding individual recruitment and timing of activation of the four abdominal muscles in humans. Fine-wire electrodes were inserted under direct vision guided by high-resolution ultra-sound into the rectus abdominis (Rectus), external oblique (Extern), internal oblique (Intern), and transversus abdominis (Transv) in nine awake healthy subjects. Airflow, end-tidal CO2, and moving-average EMG signals were recorded during 1) supine resting and CO2-stimulated ventilation and 2) resting ventilation in the standing position. During resting supine breathing, Transv showed significant phasic EMG activity during expiration. As posture changed from supine to standing, phasic activity during resting ventilation was greatest in Transv, with lesser activity in Intern and Extern, while Rectus remained inactive. As CO2 began to increase, Transv was activated first, followed by Intern, the Extern, and finally Rectus. With moderate CO2 stimulation, Transv and Intern were more active than was Extern and Rectus remained least active. EMG activities in the expiratory muscles after cessation of expiratory flow (postexpiratory expiratory activity) and in expiratory muscle activity preceding expiratory flow were observed consistently during supine stimulated ventilation and standing resting ventilation. These activities before and after expiratory airflow were prominent with stimulated ventilation during a substantial portion of inspiration, suggesting dual control of inspiratory pump action by both inspiratory and expiratory muscles, which provide acceleration and braking actions, respectively. These results suggest that in awake humans 1) during resting ventilation, expiration is an active process; 2) abdominal muscles are activated differentially; 3) Transv is the most active, Intern and Extern are intermediate, and Rectus is the least active expiratory muscle; and 4) during stimulated ventilation, inspiratory and expiratory muscles contribute dually to inspiratory pump action.

Abdominal Muscles↗
PubMed1996

Characterization of voltage-sensitive Na+ and K+ currents recorded from acutely dissociated pelvic ganglion neurons of the adult rat.

1. Electrophysiological properties of acutely dissociated neurons from the major pelvic ganglion (MPG) of the adult male rat were studied with whole cell patch-clamp recording techniques. The MPG neurons innervating the urinary bladder were labeled by retrograde axonal tracing methods with the use of a fluorescent dye, Fast Blue (FB) injected into the bladder wall and identified with a fluorescent microscope. 2. Passive and active membrane properties such as resting membrane potential, input resistance, duration of action potentials, thresholds for spike activation, or duration of afterhyperpolarization in unidentified MPG neurons were comparable with those of FB-labeled neurons innervating the urinary bladder. The action potential in both unidentified and bladder efferent MPG neurons was reversibly abolished by tetrodotoxin (TTX, 1 microM). The afterhyperpolarization of the TTX-sensitive action potential in both groups was reduced by application of Cd2+ (0.1 mM) and further suppressed by tetraethylammonium (TEA, 10 mM). Extracellularly applied TEA increased the duration of the action potential, and 4-aminopyridine (4-AP, 1 or 2 mM) also reduced the spike afterhyperpolarization and increased the spike duration. The duration of the action potential was decreased and the rate of spike repolarization was increased by approximately 2.5-fold with negative shift of membrane potential from -40 to -80 mV. 3. The isolated Na+ current was reversibly blocked by 1 microM TTX and had a mean peak amplitude of 127.3 pA/pF when activated from a holding potential of -70 mV in the external solution containing 100 mM Na+. The Na+ conductance reached half-maximal activation at a membrane potential of -21.5 mV with a slope factor of 4.9 mV. The steady-state inactivation of Na+ conductance occurred at membrane potentials more depolarized than -90 mV, and the half-maximal inactivation was obtained at -57.5 mV with a slope factor of 8.8 mV. 4. The fast-transient A-type K+ current (IA) was activated at membrane potentials more depolarized than -60 mV from a holding membrane potential of -100 mV, reached a peak amplitude within 10 ms after the onset of depolarizing voltage steps, and decayed within 20-30 ms at membrane potential depolarizations to +20 to +30 mV. The IA current activated by a voltage step to +20 mV from a holding potential of -100 mV averaged 102.1 pA/pF. The half-maximal activation of the IA conductance was obtained at a membrane potential of -21.2 mV with a slope factor of 9.9 mV. In steady-state inactivation of IA current, the half-maximal inactivation occurred at -76.5 mV and the slope factor was 8.0 mV. 5. The delayed K+ current was reduced by 25-35% by bath application of Cd2+ or the elimination of extracellular Ca2+ ions. The bath application of 4-AP (2 mM) suppressed the IA current by 75% and the delayed K+ current by 60%. Extracellularly applied TEA (10 mM) suppressed the delayed K+ current by 90%, but suppressed the IA current by only 16%. 6. These results indicate that bladder neurons and unidentified neurons in the MPG have similar properties including a TTX-sensitive Na+ current and three distinct types of voltage-sensitive K+ currents-IA current, Ca(2+)-activating K+ current, and delayed rectifier K+ current-that contribute to the repolarization phase of the action potential. These electrical properties of the MPG neurons resemble those of sympathetic neurons in the superior cervical and inferior mesenteric ganglia.

Action Potentials↗
PubMed1996

Increased cytokine gene expression in rat retina following transient ischemia.

Tumor necrosis factor (TNF) gene expression in rat retina following transient ischemia was studied by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Gene expression for other cytokines was also studied by RT-PCR. Although very little expression for TNF gene was detected in normal retina, it was markedly increased 0.5-48 h after reperfusion, with peak expression at 12 h (20-fold of control). Gene expression for interleukin-6, interferon-gamma, and transforming growth factor-beta 1 was also increased. The results provide evidence that retinal ischemia can up-regulate cytokine gene expression in the retina.

Animals↗
PubMed1996

Immunosuppression in organ transplantation.

The immunological barrier remains the major obstacle to the widespread use of transplantation as a replacement therapy for terminal organ failure. Since the first successful renal transplant, performed by Hume et al. (1952), there has been an elusive search for agents that can render the immune mechanism unresponsive to the specific alloantigen stimulus of the engrafted organ, while sparing non-specific host resistance. Immunosuppressive therapies in organ transplantation can be divided into the following four main classes: chemical (pharmaceutical), biological (immunological), physical (radiological) and surgical. Of these, chemical agents (drugs) have continued to play a principal role. The discovery of new immunosuppressive drugs such as corticosteroids, ciclosporin, azathioprine and FK506 have been epoch-making discoveries at each stage in the history of clinical organ transplantation. The recent immunosuppressants were designed to focus their action selectively on T and/or B cells by inhibiting cytokine synthesis (ciclosporin, FK506), cytokine action (rapamycin), or cell differentiation (15-deoxyspergualin) pathways, rather than to act on immune systems in a non-selective fashion. At the present time, however, there is no single panacea. To achieve the maximum preventive and therapeutic effects with the minimum toxicity, two or more immunosuppressive drugs are used appropriately in combination, taking the mechanisms of action of each into consideration.

Adrenal Cortex Hormones↗
PubMed1996

[A population survey on bone mineral density in a fishing village in Wakayama prefecture. (Part 1) Distribution of bone mineral density by sex and age based on a representative sample of the community].

To establish reference values for bone mineral density (BMD), a population survey was carried out in a fishing community in Wakayama Prefecture. The BMD measurements of the lumbar spine (L2-L4) and proximal femur (femoral neck, trochanter and Ward's triangle area) were performed by sex and age, using dual-energy X-ray absorptiometry. Four hundred subjects, aged 40 to 79 years, were recruited randomly to give 50 persons in each of eight age-sex strata from a list of 2,261 residents (1,028 men and 1,233 women) living in a fishing village. The validity of sampling methods was assessed using a questionnaire about lifestyle factors, which was used for all residents aged from 40 to 79 years in the baseline survey. There were no significant differences between the subjects for BMD measurements and all the residents of the community in the frequencies of past history of diseases, healthy habits, food intakes, and rates of smoking, alcohol drinking, coffee and green tea consumption. These findings suggested that the present study population could be considered representative of samples obtained from the entire population in the fishing community. The results of BMD measurements in these subjects, who were selected at random, showed that except for a slightly high BMD of the lumbar spine in men in their 60's, the mean BMD of the lumbar spine and the three proximal segments of the femur decreased with increasing age in both sexes.

Adult↗