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Biomedical subjects

A Ikeda

Publications and source records attributed to A Ikeda.

At least 253 records · Page 14Linked to original sources

Molecular cloning of DNA for inhibin alpha-subunit from equine ovary.

cDNA encoding equine inhibin alpha-subunit precursor protein was isolated from an equine ovarian cDNA library. For screening, the DNA probe was amplified by the RT-PCR using primers designed based on the rat inhibin alpha-subunit cDNA sequence. Out of 1.2 x 10(5) plaques screened, 19 positive clones were isolated, and one of these clones (Eq-alpha-11) contained a complete open reading frame encoding 367 amino acids. The similarity of the deduced amino acid sequences of both equine inhibin alpha-subunit precursor protein and the mature protein were greater than 80% to those of other six mammalian species, including bovine, porcine, ovine, human, rat and mouse. Northern blot analysis revealed that a single major band at 1.5 kb was present in the RNA samples both from equine follicles and testes.

Amino Acid Sequence↗

Bronchodilating effects of combined therapy with clinical dosages of ipratropium bromide and salbutamol for stable COPD: comparison with ipratropium bromide alone.

Several studies have suggested that anticholinergics are at least equal to or may be superior to beta agonists in the treatment of stable COPD. However, since most previous studies have been performed to evaluate the bronchodilating effects of these two agents at relatively high doses, the clinical value of combining these two agents still is under debate. The purpose of this study was to determine if combination therapy with ipratropium bromide and salbutamol, in clinically available dosages, is superior in bronchodilation to ipratropium bromide alone. Twenty-six male patients (mean age, 67.5 +/- 5.9 years; FEV1, 0.87 +/- 0.32 L) with stable COPD were studied in randomized, double-blind, placebo-controlled experiments. On five separate days, all the patients received one of the following: (1) 40 micrograms ipratropium bromide, (2) 80 micrograms ipratropium bromide, (3) 40 micrograms ipratropium bromide plus 200 micrograms salbutamol, (4) 80 micrograms ipratropium bromide plus 400 micrograms salbutamol, or (5) placebo, using metered-dose inhalers (MDIs). Spirometry was assessed before and 15, 30, 60, 90, and 120 min after inhalation. Positive FEV1 responses to combined dosages of 80 micrograms ipratropium bromide and 400 micrograms salbutamol were significantly greater than responses to any other treatment regimen. Significantly greater responses also were achieved by combining 200 micrograms salbutamol with 40 micrograms ipratropium bromide compared with 40 micrograms ipratropium bromide alone. Combination therapy with 200 micrograms salbutamol and 40 micrograms ipratropium bromide produced a significantly greater effect on forced vital capacity than therapy with 80 micrograms ipratropium bromide alone. No significant differences were found between the responses induced by therapy with 80 and 40 micrograms ipratropium bromide. No adverse reactions to any regimen were noted throughout the study. In conclusion, combining the standard dosages of ipratropium bromide and salbutamol may provide greater bronchodilation than doubling the standard dosage of ipratropium bromide in patients with COPD.

Aged↗

The additive effect of theophylline on a high-dose combination of inhaled salbutamol and ipratropium bromide in stable COPD.

STUDY OBJECTIVE: To determine the additive effect of oral theophylline in patients with stable COPD who received both inhaled salbutamol, 400 micrograms, and ipratropium bromide, 80 micrograms, four times daily administered with a metered-dose inhaler. DESIGN: Twenty-four male patients with stable COPD (FEV1, 0.96 +/- 0.43 L; 36.8 +/- 17.0 percent predicted [% pred]) completed a randomized, double-blind, placebo-controlled crossover trial with oral theophylline for 4 weeks. MEASUREMENTS AND RESULTS: The average serum theophylline level was 15.0 +/- 5.5 micrograms/mL during treatment. On the whole, without inhalation of bronchodilators, FEV1 was 0.93 +/- 0.42 L during the placebo period and 1.00 +/- 0.43 L (significantly different from placebo; p < 0.01) during the theophylline period. At 15 and 60 min after inhalation of salbutamol, 400 micrograms, and ipratropium, 80 micrograms, the FEV1 with placebo was 1.12 +/- 0.43 L and 1.14 +/- 0.46 L, respectively, and the FEV1 with theophylline was 1.18 +/- 0.45 L (p < 0.01) and 1.20 +/- 0.47 L (p < 0.01), respectively. Daily peak expiratory flow rate also improved. Daily symptom scores were not significantly different between theophylline and placebo periods. Nevertheless, eight patients reported a subjective benefit during the theophylline administration period, and they were thus considered subjective responders. While FEV1 after inhalation was significantly improved during the theophylline periods in subjective responders (change in FEV1 between theophylline and placebo treatment 15 min after inhalation, 3.1 %pred; 60 min, 3.5 %pred), postbronchodilator FEV1 was not significantly different between the placebo and theophylline periods in subjective nonresponders (15 min, 1.7 %pred; 60 min, 1.6 %pred). CONCLUSIONS: On the whole, theophylline has a small bronchodilating effect but does not improve the symptoms of patients with stable COPD. However, one third of patients with COPD may respond subjectively to theophylline. The additive bronchodilating effect of theophylline may be related to the symptomatic improvement in subjective responders.

Administration, Inhalation↗

[Effect of one year of treatment with inhaled beclomethasone dipropionate on airway hyperresponsiveness in stable chronic asthma].

To study the effects of an inhaled steroid on airway hyperresponsiveness (AHR) in chronic stable asthma, AHR was measured every month for 1 year in seven patients after their asthma had stabilized, i.e., when they had no wheezing or dyspnea, and their peak expiratory flow rates (PEFR) were at least 80 percent of the highest value. During the study period, no patient wheezed or had dyspnea, and daily variation in PEFR was less than 20 percent. In six patients, FEV1 was stable, and PEFR was always at least 80 percent of the highest value. AHR became less severe, by a factor of at least 2, in five of these six patients, but one patient's condition did not improve. The one patient whose PEFR fell below 80 percent of the highest value had more than a 4-fold increase in the severity of AHR. In conclusion, the severity of AHR can be reduced, even in patients with chronic stable asthma, if daily PEFR can be maintained in an optimal range by long-term use of inhaled corticosteroids.

Administration, Inhalation↗

[Cerebral blood flow and metabolism in Lafora disease].

An 18-year-old male manifesting intellectual deterioration and negative myoclonus was diagnosed as Lafora disease by the demonstration of Lafora bodies in the skin and muscle biopsy. The cortical evoked potential to electric stimulation of the median nerve at wrist showed the giant SEP, suggesting hyperexcitability of the sensory motor cortex. Cerebral blood flow, and cerebral glucose and oxygen metabolism were investigated by positron emission tomography (PET) in order to clarify the pathophysiological process in Lafora disease. The result showed diffusely decreased cortical glucose metabolic rate and cerebral blood flow, and moderately lowered oxygen metabolic rate. There was no increase in blood flow or glucose and oxygen metabolism in the sensorimotor cortex in spite of the presence of giant SEP. The ratio of the glucose to oxygen metabolism was not different from the mean value obtained from nine normal subjects. Based on these findings and review of the literature, it is unlikely that there is a significant deficit in cortical energy metabolism in patients with Lafora disease and it would be less plausible to have some enzymatic deficits in glucose metabolic process.

Adolescent↗

[Efficacy of high-dose beclomethasone in patients with stable chronic obstructive pulmonary disease].

To study the role of inhaled steroids in treating patients with chronic obstructive pulmonary disease (COPD), 1.6 mg of beclomethasone dipropionate (BDP) were given for 2 weeks after 0.5 mg/kg of oral prednisolone (PSL) for 2 weeks to 43 patients with COPD (mean age 68.7 +/- 5.2 years, mean baseline FEV1, 1.13 +/- 0.44 L). When responders to a corticosteroid (PSL or BDP) were defined as those with a post-steroid EFV1/baseline FEV1 > or = 115% and a post-steroid FEV1-baseline FEV1 > or = 0.2 L, 12 out of 43 patients responded to 30 mg of PSL for 2 weeks and 13 responded to 1.6 mg of BDP for 2 weeks. We considered those 17 patients who responded to 2 weeks of PSL or 2 weeks of BDP or both, to be possible steroid responders, and they continued inhaling BDP for 4 more weeks. In 8 of these 17 patients (19%), FEV1 had increased by the end of the 6 weeks. Inhaled BDP was considered useful in treating some patients with COPD.

Administration, Inhalation↗

[Effect of theophylline on disturbances of ventilation and of gas exchange during exercise in patients with pulmonary emphysema].

Factors limiting exercise were studied in 23 patients with pulmonary emphysema, and the effects of theophylline on exercise tolerance and on hypercapnic ventilatory response were studied in 16 patients with pulmonary emphysema. Exercise in these patients was limited by inability to increase tidal volume and by disturbances of gas exchange, as indicated by low PaO2, high AaDO2, and high PaCO2 during exercise, and by low diffusing capacity. Theophylline increased tidal volume during exercise, but it did not improve oxygenation during exercise. Theophylline improved exercise tolerance and hypercapnic ventilatory response. The percent increases in VEmax and in VO2max after theophylline administration correlated significantly with the percent increase in the ratio of mouth occlusion pressure to PACO2 during rebreathing. These results indicate that exercise tolerance in patients with pulmonary emphysema can be improved by theophylline, probably because of an increase in ventilatory drive.

Aged↗

[Noninvasive study of cortical neuronal mechanism in voluntary movements: role of basal ganglia and cerebellum].

Voluntary movements can be classified into the two categories depending on how those are initiated; ones initiated internally, and others triggered or paced by external stimuli. Central neuronal mechanisms involved in those preparation and execution could be represented by movement-related cortical potentials (MRCP) or Bereitschaftspotential (BP), and contingent negative variation (CNV), respectively. The both potentials, as the field potentials, can be recorded with long time constant, and represent transient changes of the membrane potentials of the cortical neurons. In patients with the lesion at the cerebellar efferent system, the BP disappeared completely whereas the late CNV was normally seen. In patients with parkinsonism, in contrast, the late CNV was significantly smaller in amplitude in severe than in mild symptom group. Recent subdural recording in epilepsy patients demonstrated that the BP and late CNV were commonly generated from the primary and supplementary motor areas, and that late CNV also arose from the frontal association cortices (mesial, basal and lateral prefrontal areas). It is therefore suggested that subcortical generating mechanism is different for the late CNV and BP although both commonly share at least some cortical generators, and that the basal ganglia are most likely responsible for the generation of the late CNV and the cerebellar efferent system for the generation of the BP.

Basal Ganglia↗

[High-dose inhaled beclomethasone dipropionate and maximal improvements in patients with stable chronic obstructive pulmonary disease].

High doses of inhaled beclomethasone dipropionate (BDP) are effective in some patients with chronic obstructive pulmonary disease (COPD). However, dose-response data for this agent are limited. To determine whether patients receive maximum benefit from 1600 micrograms of BDP, we performed a randomized, double-blind, placebo-controlled, cross-over trial. Twenty-one patients with stable COPD [mean +/- SD: age, 69.1 +/- 6.8 yrs; FEV1, 0.86 +/- 0.28 L] were treated with both inhaled bronchodilators and 1600 micrograms of BDP daily for at least 3 months. Each patient received 30 mg of oral prednisolone or a placebo for 3 weeks. In addition to end-point spirometric assessments daily peak expiratory flow rate, symptom scores, and scores on a chronic respiratory disease questionnaire were recorded for the last week of each 3-week period. Oral prednisolone did not improve FEV1, FVC, symptoms or scores on the questionnaire. We conclude that 1600 micrograms of BDP in addition to inhaled bronchodilators produces maximal improvements in stable patients with COPD.

Administration, Inhalation↗

Secretory production of chicken ovomucoid domain 3 by Escherichia coli and alteration of inhibitory specificity toward proteases by substitution of the P1 site residue.

Ovomucoids are commonly present in bird egg white and exhibit inhibitory activity toward various serine proteases. To investigate the structure-function relationship of ovomucoid domain 3, we established a secretory expression system for the chicken ovomucoid domain 3 (OMCHI3)-encoding gene in Escherichia coli by ligating it downstream from the tac promoter and signal peptide of E. coli alkaline phosphatase. E. coli JM105 was transformed with the resulting plasmid and induced with 1 mM isopropyl-beta-D-thiogalactopyranoside (IPTG). The mature OMCHI3 was detected in the culture supernatant, and was purified to homogeneity by three-step chromatography. Amino-acid sequence analysis showed that processing by the signal peptidase was carried out exactly at the expected site. Measurements of circular dichroism spectra and inhibitory activity indicated that OMCHI3 was produced in the properly folded form. Furthermore, site-specific replacement of the Ala residue at the P1 site with Met or Lys resulted in acquisition of inhibitory activity toward chymotrypsin or trypsin, respectively, indicating that the P1 site is the predominant determinant for inhibitory specificity.

Amino Acid Sequence↗

Dissociation between contingent negative variation and Bereitschaftspotential in a patient with cerebellar efferent lesion.

Contingent negative variation (CNV) and Bereitschaftspotential (BP) were from the scalp in a patient with a discrete infarct in the mesial tegmentum of the midbrain involving the decussation of the superior cerebellar peduncle. Bereitschaftspotential in association with hand movements was completely absent while CNV was normally present at the frontocentral midline. This indicates that CNV is, as opposed to BP, generated without cerebro-cerebellar interactivation, suggesting different generating mechanisms.

Cerebellar Diseases↗

Cortical reflex negative myoclonus.

Three patients with progressive myoclonic epilepsy (PME), two of them clinically manifesting only negative myoclonus and the other manifesting both positive and negative myoclonus, were electrophysiologically investigated, and compared with two other patients with PME presenting with only positive myoclonus. Electric stimulation of the median nerve during sustained active wrist extension in the three patients with negative myoclonus often elicited a short lapse of the posture in the stimulated hand associated with a silent period in the muscle discharge with or without being preceded by an abrupt increase in the muscle discharge (C reflex). The occurrence of the stimulus-induced silent period was significantly correlated with that of the giant somatosensory evoked potentials (SEPs), and in two patients the silent period was elicited also in the opposite (non-stimulated) hand when the giant SEP was recorded at the hemisphere ipsilateral to the stimulus as well. In one patient, the duration of the silent period was positively correlated with the amplitude of the cortical SEP. Furthermore, the duration of the induced silent period was closely related to the recovery function of SEP in each individual case. In contrast, in the two patients manifesting only positive myoclonus, the silent period was not elicited by the peripheral stimulation, and the somatosensory cortex was hyperexcitable immediately after the peripheral stimulus. Thus, this stimulus-sensitive negative myoclonus is mediated by a transcortical reflex mechanism, and corresponds to the negative form of the cortical reflex myoclonus ('cortical reflex negative myoclonus').

Adult↗

Generator mechanism of pain-related evoked potentials following CO2 laser stimulation of the hand: scalp topography and effect of predictive warning signal.

In order to clarify the generator mechanism of pain-related evoked potentials (pain EPs), we studied the scalp topography of the pain EPs following CO2 laser stimulation of hand dorsum by using balanced sternovertebral electrodes as the noncephalic reference in 11 normal volunteers. We also examined the effects of predictive warning signal (light-emitting diode) on the pain EPs. In both the warned and unwarned conditions, all of the 22 hand stimulations showed a large negative component (N2) at the peak latency of about 213 ms followed by a large positive component (P2) at the peak latency of about 329 ms. A preceding small negative component (N1) at the peak latency of about 148 ms was detected in 12 of the 22 hand stimulations in the warned condition and in 13 of the 22 hand stimulations in the unwarned condition. P2 was significantly larger and occurred earlier in the warned condition than in the unwarned condition, whereas other components did not differ between the two conditions, suggesting that an increased attention of the subject to the stimulus influenced the generator mechanism of the P2 component. With regards to the scalp topography, N2 was maximal at Cz and widespread transversely to both sides, whereas P2 was maximal at Cz or Pz and spread more posteriorly than N2. These findings suggest that P2 is generated by a different mechanism from N2 and is most likely associated with pain-related cognitive function. N1 was localized to the contralateral central and midtemporal areas, confirming that the nociceptive inputs are perceived in the sensory cortex in humans. The question as to whether the N1 component is generated in the hand area of the primary somatosensory cortex or in the secondary somatosensory cortex, or in both areas, remains to be solved.

Adult↗

Automatic detection of P300 in single sweep records of auditory event-related potential.

In the conventional recording of event-related potentials (ERPs) by the "oddball" paradigm, the subject may employ different strategies for processing one stimulus from the other even within the same session because of variable psychological state. Hence, "averaging" may not necessarily be suitable for recording ERP. We have therefore established a method for single trial recording of auditory ERPs by processing the EEG data through discrete Fourier transform followed by inverse discrete Fourier transform with the low pass filter of 8 Hz (digital filter). Each single sweep response of the processed data was visually evaluated as to whether it contained P300 or not by three investigators who were made completely blind with respect to the category of each response. As the result, a positive peak at a latency of 200-500 ms was recognized in the single sweep responses to target stimuli at a significantly greater frequency (40-60%) than in those to nontarget stimuli (0-18%). Then a new method for the automatic detection of P300 was established based on the data of 11 subjects belonging to the training group, by taking into account, in addition to the correlation coefficient analysis in which the template was computed specifically for each subject, other criteria with respect to the amplitude and waveforms, so that a good agreement with the results of visual inspection as to the presence or absence of P300 could be achieved for both target and nontarget responses. This automatic analysis method was successfully applied to five other subjects of the test group. The peak latency and amplitude of the detected positive peaks significantly varied among single target responses even within the same session. The reaction time significantly correlated positively with the peak latency of the detected positive peaks and negatively with the amplitude of those peaks, supporting the usefulness of the present method.

Adult↗

Bronchial responsiveness and acute bronchodilator response in chronic obstructive pulmonary disease and diffuse panbronchiolitis.

BACKGROUND: Diffuse panbronchiolitis (DPB) is characterised clinically by chronic airflow limitation and respiratory tract infection, and pathologically by chronic bronchiolar inflammation. To elucidate the functional differences between chronic obstructive pulmonary disease (COPD) and DPB the bronchial responsiveness to methacholine was compared in 64 patients with COPD and 32 patients with DPB, and the bronchodilator response was compared in 72 patients with COPD and 49 with DPB. METHODS: Bronchial responsiveness to methacholine was determined by the dosimeter method and expressed as PD20FEV1, and bronchodilator response was measured as the change in percentage predicted response with 5 mg nebulised salbutamol. RESULTS: Baseline FEV1 was similar in the two groups of patients. Patients with COPD were more responsive to methacholine than were those with DPB (geometric mean PD20FEV1 8.87 v 48.0 cumulative units). Reversibility of air flow obstruction, expressed as the difference between the percentage predicted postbronchodilator FEV1 and prebronchodilator FEV1, was significantly larger in patients with COPD than in those with DPB (7.87 (6.52)% v 4.16 (4.43)%). CONCLUSIONS: The observation that patients with DPB differ substantially in bronchial responsiveness from those with COPD is thought to reflect the difference in the mechanisms of these two diseases--that is, airway disease in DPB and more parenchymal disease in the group of patients with COPD. The nature of bronchiolar inflammation in COPD and DPB is also different, possibly explaining the difference in bronchial responsiveness. More fixed airflow limitation as a result of structural bronchiolar lesions in DPB will explain the smaller reversibility of airflow obstruction.

Aged↗

Arteriographic study of the arterial supply of the foot in one hundred cadaver feet.

The arterial supply of 100 human cadaver feet (87 cadavers) was investigated by stereoscopic arteriography and was compared phylogenetically to that of the macaque foot. The deep plantar arch was always well developed and complete, whereas the superficial plantar arch was usually slender and incomplete. The first proximal perforating artery arising from the dorsalis pedis artery formed the main component of the deep plantar arch in 82% of the feet. The second proximal perforating artery arising from the dorsal rete contributed to the deep plantar arch in 43% of the feet, and formed most of the arch in one foot. The dorsal rete was classified into four groups of variants based on the arterial source of the second dorsal metatarsal artery. These were the arcuate artery (25%), distal lateral tarsal artery (12%), proximal lateral tarsal artery (6%), and nondorsal rete (57%) variants. In the first intermetatarsal space, the dorsal and plantar metatarsal arteries shared a common trunk in 54% of the feet, but this did not occur in the other intermetatarsal spaces. The second dorsal metatarsal artery arose from the dorsal rete in 43% of the feet, and this artery was quite large, sometimes being the largest of all the dorsal and plantar metatarsal arteries. Variations of the arterial supply found in humans sometimes resembled the typical pattern found in the macaque.

Adult↗

Oxitropium bromide improves exercise performance in patients with COPD.

Inhaled anticholinergics may be the first-line therapy for stable COPD. However, the effect of inhaled anticholinergic agents on exercise capacity is still controversial. Fourteen patients with stable COPD (age, 64.6 +/- 5.9 years) completed a randomized, double-blind placebo-controlled crossover trial. All the patients were studied by symptom-limited progressive cycle ergometry before and 90 min after the inhalation of either oxitropium bromide, 800 micrograms, or an identical placebo. Spirometry was assessed before and after each exercise test. While FEV1 averaged 0.85 +/- 0.34 L at 90 min after the inhalation of placebo, FEV1 was 1.01 +/- 0.41 L at 90 min after the inhalation of oxitropium, 800 micrograms (significant from placebo, p < 0.001). The maximal workload of 94.0 +/- 25.8 W after oxitropium administration was significantly greater than the 87.6 +/- 24.7 W measured after placebo (p < 0.01). The maximal minute ventilation was 40.2 +/- 12.3 L/min after oxitropium inhalation and 36.8 +/- 10.5 after placebo inhalation (p < 0.05). The differences in maximal oxygen consumption, maximal carbon dioxide production, and maximal heart rate between oxitropium and placebo inhalation also were statistically significant (p < 0.05, p < 0.05, and p < 0.01, respectively). There was a significant correlation between the change in maximal workload and the change in FEV1 before and after inhalation (r = 0.625, p < 0.01). The inhalation of oxitropium bromide, 800 micrograms, can improve the exercise capacity of patients with stable COPD. It is suggested that the effect is due to the bronchodilation induced by this drug.

Administration, Inhalation↗