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N Yoshimura

Publications and source records attributed to N Yoshimura.

At least 289 records · Page 16Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

[A population survey on bone mineral density in a fishing village in Wakayama Prefecture (Part 2); The analysis of the risk factors affecting the bone mineral density].

The purpose of this study was to detect factors affecting lumbar bone mineral density (BMD) of general inhabitants in a rural community. A cohort consisting of 2261 inhabitants aged 40-79 years was set up based on the resident registration in Taiji town, Wakayama Prefecture in 1992. Fifty men and 50 women in each of four age strata (40-49, 50-59, 60-69, 70-79), totaling 400 inhabitants, were selected randomly. After completion of a questionnaire by an interviewer, items about physical characteristics such as height, body weight, wrist length and grip power were measured. Examination of BMD of the lumbar spine and proximal femur by dual energy X-ray absorptiometry was performed. Correlation coefficients between BMDs and values of physical characteristics were determined. Lumbar BMD was examined to determine whether the following factors were positive or negative: past history, alcohol consumption, smoking habit, dietary habit, exercise, and in addition, pregnancy times and menstrual status for women. Among the values of physical characteristics, body weight was the most closely correlated with lumbar BMD. The items that showed significantly high values as factors affecting lumbar BMD were a past history of diabetes mellitus (men and women in their 70s), and exercise (men in their 50s and women in their 40s). Regarding pregnancy times and menstruation, BMD in women with a history of childbirth was significantly higher than that in those without the history among the women in their 70s. Although the BMD in the women with lactation was significantly lower than that in those without it among the women in their 40s, there was no difference in BMD between the women with and without the history who were 50 years old or over. The effect of menstrual status was investigated according to years after menopause in the women in their 50s. BMD was significantly lower in the women with ar least six years after menopause than in those within five years.

Adolescent↗

Profile of chest injuries arising from the 1995 southern Hyogo Prefecture earthquake.

STUDY OBJECTIVE: To better understand the types of chest injuries that are likely to occur following a major earthquake in the urban environment, we analyzed the pattern of chest injuries arising from the earthquake that struck the southern part of Hyogo Prefecture in Japan at 5:46 AM on January 17, 1995 and registered 7.2 on the Richter scale. DESIGN AND SETTING: The medical records of 487 patients with injuries who were referred to Kobe University Hospital from January 17 to January 23 were reviewed. RESULTS: Of the 487 patients, 63 (12.9%) were found to have chest injuries. Of these 63, eight patients with severe chest compression were dead on arrival at the hospital. Eight patients were admitted to our hospital, two of whom developed crush syndrome. The remaining 47 (74.6%) patients had light to moderate injuries and were treated in the emergency department on an outpatient basis. CONCLUSIONS: Minor trauma was the most common type of chest injury. However, there were severely injured patients who were trapped in collapsed buildings.

Adolescent↗

Recurrent histiocytic necrotizing lymphadenitis (Kikuchi's disease) in an human T lymphotropic virus type I carrier.

We describe a case of recurrent histiocytic necrotizing lymphadenitis (HNL) with aseptic meningitis. The patient was a 46-year-old male and a carrier of human T lymphotropic virus type I (HTLV-I). The patient had a past medical history of at least three relapses of HNL. In addition, his sister, who was also an HTLV-I carrier, had recurrent clinical episodes consistent with those of HNL, suggesting familial HNL occurrence. This observation suggests the possibility that HTLV-I infection is relevant to the pathogenesis of HNL.

Antibodies, Viral↗

Endothelin protein expression in tear glands of the rabbit.

PURPOSE: Endothelin-1 (ET-1) has been found to accelerate rabbit corneal epithelial wound healing in vivo and proliferation of rabbit and bovine epithelial cells in vitro. We have now determined that endothelin-like immunoreactivity (ET-LI) is present in the tear fluid of New Zealand white rabbits, and we have addressed the question of whether it is produced by the tear glands (lacrimal gland and Harderian gland). METHODS: Tears were obtained with capillary pipettes and lacrimal gland fluid was collected by cannulation. ET-LI was determined with a sandwich-enzyme immunoassay. The reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to determine if there are gene transcripts for prepro ET-1 in tear glands. ET-LI in the tear glands was evaluated using immunohistochemistry. RESULTS: The tears contained 13.85 +/- 3.94 pg/ml (mean +/- SEM, n = 6) ET-LI and the lacrimal gland fluid had 24.90 +/- 6.00 pg/ml (n = 6). The plasma contained 0.89 +/- 0.20 pg/ml (n = 6). Gene transcripts were identified for prepro ET-1 in the lacrimal and Harderian glands. Specific staining for ET-LI was found in the epithelial cells of the ducts of the lacrimal gland and the acinar cells of the Harderian gland. CONCLUSIONS: The higher concentrations of ET-LI in the tears and the lacrimal gland fluid than in plasma along with prepro ET-1 gene transcripts in the tear glands suggest that they secrete ET-1.

Animals↗

Role of nitric oxide synthase isozymes in endotoxin-induced uveitis.

PURPOSE: The authors previously reported that in vitro treatment with N(G)-nitro L-arginine (L-NNA), an inhibitor of nitric oxide synthase (NOS), reduces aqueous humor (AH) protein and cellular infiltration in endotoxin-induced uveitis in the rat eye. The objective of the current study was to determine the role(s) of respective major forms (constitutive and inducible) of NOS by comparing the effects of relatively selective inhibitors of these NOS isozymes. METHODS: N(G)-nitro L-arginine (L-NNA), a relatively selective inhibitor for constitutive NOS (c-NOS), and N-iminoethyl L-ornithine (L-NIO), a more selective inhibitor for inducible NOS (i-NOS), were administered in vivo. Male Lewis rats were footpad injected with bacterial lipopolysaccharide (LPS, 200 microgram) and were injected intraperitoneally at 0 hours, 6 hours, or both, after LPS injection with 10 mg of NIO, NNA, or saline as a control. Nitric oxide synthase activity in the ocular tissue and AH protein and cell content were determined at various times after treatment with LPS. RESULTS: After in vivo treatment, L-NIO was found to be a more potent inhibitor than L-NNA for ocular i-NOS (87% versus 43% inhibition), and L-NNA was more potent than L-NIO for ocular c-NOS (81% versus 39%). Two injections of L-NNA, one at time 0 and one 6 hours after LPS injection, inhibited the AH protein increase by 71%, but L-NIO did so by only 30%. L-NNA inhibited cellular infiltration by 86%, whereas L-NIO had no significant effect on cellular infiltration. A significant inhibition of cellular infiltration and AH protein increase also was observed with a single injection of 10 mg of L-NNA but not of L-NIO when the inhibitors were given simultaneously with LPS. Thus, reduction of uveitis symptoms correlates with the inhibition of c-NOS. CONCLUSIONS: The constitutive form of NOS in ocular tissue, presumably in vascular endothelial cells, appears to play a critical role at the onset of the development of endotoxin-induced uveitis.

Animals↗

[Diagnosis of lung cancer using functional image of 201Tl SPECT with parameter of 201Tl retention--evaluation of its applicability to post irradiated lung cancer].

Thallium-201 (201Tl) SPECT is a useful method for detecting lung cancer. Moreover, the 201Tl Retention Index (R.I.) reported by Tonami et al is now available for differentiating pulmonary lung cancer from benign lesions. The diagnosis of recurrent tumors is, however, difficult to establish as they are often shaded by radiation pneumonitis or fibrosis. Therefore, we employed functional images (F.I.) obtained using as parameter a modified version of the R.I. First we indicated the statistical value of untreated solitary lung tumor as follows: sensitivity 84.6%, specificity 80.0%, and accuracy 83.3%. In our assessment, the lesions with tumor size over 2.0 cm and R.I. by Tonami et al over 12.7 were detected as positive images. Secondly in assessment of 22 cases (23 lesions) of post irradiated lung cancer, the results obtained were: sensitivity 80.0%, specificity 92.3%, and accuracy 87.0%. 201Tl SPECT functional images seem to be useful for the diagnosis of recurrent lung cancer by shaded radiation pneumonitis and fibrosis.

Adenocarcinoma↗