Plasma beta-endorphin levels in patients with gynaecological malignancies.
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Biomedical subjects
Publications and source records attributed to Y Kikuchi.
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Mouse IL-5 (mIL-5) acts on B cells and eosinophils to induce growth and differentiation through the mIL-5 specific receptor (mIL-5R). The functional high-affinity mIL-5R is a heterodimer composed of alpha and beta chains. We investigated the expression of mIL-5R and the responsiveness of B cells and eosinophils to mIL-5 in X-linked immunodeficient (xid) mice. mIL-5R expression analyzed by using mAbs specific for alpha and beta chains revealed that xid B cells had fewer mIL-5R alpha +mIL-5R beta + than BALB/c B cells. In particular, a decrease in the number of peritoneal mIL-5R+ B cells among Ly-1 B cells (known as B-1 cells) was remarkable. Furthermore, the frequency of precursors of mIL-5 responsive B cells in xid mice was approximately 100-fold lower than that of BALB/c mice. Interestingly, sorted mIL-5R+ peritoneal B cells from xid mice displayed a low response to mIL-5. Intraperitoneal injection of mIL-5 into BALB/c mice induced polyclonal IgM production and an increase in the number of eosinophils. The same regimen failed to induce an increase in the same parameters in xid mice. However, xid mice showed mIL-5-induced eosinophilia in peripheral blood to a similar extent as BALB/c mice. Eosinophils from mIL-5-injected xid mice expressed both alpha and beta chains of mIL-5, and responded to mIL-5 with prolonged in vitro survival.
We have expressed truncated forms of BTEB and Sp1 in Escherichia coli and investigated the DNA-binding properties of the two proteins. The two proteins as well as their chimeric proteins protected the same DNA region in the BTE sequence (a GC box in the P-4501A1 gene) as examined by ortho-phenanthroline-Cu footprinting. The region overlapped nearly perfectly with the GC box consensus sequence. Methylation interference footprinting revealed that all the guanines within the region and two other guanines in the close vicinity interacted with the proteins. Competitive gel mobility shift assay using various synthetic oligonucleotides of the GC box sequences as the competitors demonstrated that BTEB and Sp1 have similar sequence specificities for DNA binding. We have purified the bacterially expressed BTEB and measured the dissociation constant of the BTEB-BTE complex using gel mobility shift assay. The dissociation constant was (3.0 +/- 1.0) x 10(-10) M and was comparable to that of Sp1 binding to a GC box. Taken together, these findings indicate that the binding modes of BTEB and Sp1 to the GC box are similar to each other.
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This assay method allows a simultaneous determination of imipramine, desipramine, their 2-hydroxylated metabolites, and imipramine-N-oxide in 0.5 ml of plasma or 0.1 ml of urine within 35 min by an ion-paired, reversed phase (C18) high-performance liquid chromatography (HPLC) with electrochemical detection. The analytes are extracted from alkalinized plasma or urine with 5 ml of a 90/10 mixture (by vol) of diethyl either/2-propanol, back-extracted into 0.5 ml of 0.1 mol/L phosphoric acid. Urine samples are enzymatically treated with beta-glucuronidase/arylsulfatase before extraction. The electrochemical detection is performed with a glassy carbon electrode set at +0.85 V against the Ag/AgCl reference electrode. Recoveries for the analytes and the internal standard (propericiazine) from plasma or urine ranged from 66.4 to 105.7% with coefficients of variation (CVs) of < 6.8%. The intra- and interassay CVs for the analytes were < 17.4% in plasma and < 14.2% in urine. The limits of determination (a signal-to-noise ratio of 3) for imipramine, desipramine, 2-hydroxyimipramine, 2-hydroxydesipramine, and imipramine-N-oxide were 0.5, 0.3, 0.02, 0.02, and 1.0 microgram/L, respectively. Only four of the 23 psychotropic drugs, which might be coadministered with imipramine or desipramine, were considered to be the possible sources to interfere with the assay. We evaluated clinical applicability of this method by determining plasma concentration- and urinary excretion-time courses of the respective analytes in an extensive and a poor metabolizer of the debrisoquine/sparteine-type oxidation after a single oral dose of imipramine HCl (25 mg). The present method appears to be suitable not only for the therapeutic drug monitoring of imipramine and its active metabolites but also for studying the pharmacogenetically related metabolism of imipramine or desipramine.
BACKGROUND: It is well known that upper airway resistance increases with postural change from a sitting to supine position in patients with obstructive sleep apnoea (OSA). It is not known, however, how the postural change affects the ventilatory and occlusion pressure response to hypercapnia in patients with OSA when awake. METHODS: The responses of minute ventilation (VE) and mouth pressure 0.1 seconds after the onset of occluded inspiration (P0.1) to progressive hypercapnia (delta VE/delta PCO2, delta P0.1/delta PCO2) both in sitting and supine positions were measured in 20 patients with OSA. The ratio of the two (delta VE/delta P0.1) was obtained as an index of breathing efficiency. The postural changes in response to carbon dioxide (CO2) after uvulopalatopharyngoplasty (UPPP) were also compared in seven patients with OSA. RESULTS: There were no significant changes in the resting values of end tidal PCO2, P0.1, or VE between the two positions. During CO2 rebreathing, delta VE/delta PCO2 did not differ between the two positions, but delta P0.1/delta PCO2 was significantly higher in the supine than in the sitting position (supine, mean 0.67 (SE 0.09) cm H2O/mm Hg; sitting, mean 0.57 (SE 0.08) cm H2O/mm Hg), and delta VE/delta P0.1 decreased significantly from the sitting to the supine position (sitting, 4.6 (0.4) l/min/cm H2O; supine, 3.9 (0.4) l/min/cm H2O). In seven patients with OSA who underwent UPPP, delta VE/delta P0.1 improved significantly in the supine position and postural change in delta VE/delta P0.1 was eliminated. CONCLUSIONS: These results suggest that in patients with OSA the inspiratory drive in the supine position increases to maintain the same level of ventilation as in the sitting position, and that the postural change from sitting to supine reduces breathing efficiency. Load compensation mechanisms of patients with OSA appear to be intact while awake in response to the rise in upper airway resistance.
To examine the effects of sustained hypoxia on upper airway and chest wall muscle activity in humans, we measured genioglossus muscle (GG) activity, inspiratory intercostal muscle (IIM) activity, and ventilation during sustained hypoxia in 17 normal subjects and 17 patients with obstructive sleep apnea (OSA). The trial of sustained hypoxia was performed as follows: after an equilibration period of 3 min, isocapnic hypoxia (arterial O2 saturation = 80 +/- 2%) was maintained for 20 min. GG EMG was measured with a fine-wire electrode inserted percutaneously, and IIM EMG was measured with surface electrodes. Ventilatory response to sustained hypoxia was initially increased and subsequently decreased. Stable phasic GG activity during spontaneous tidal breathing was observed in 6 normal subjects and 10 patients with OSA. Responses of GG and IIM activities to sustained hypoxia showed a biphasic response qualitatively similar to the ventilatory response in these 16 subjects. The absolute value of the subsequent decline in GG activity was similar to that of the initial increase, whereas the subsequent decline in IIM activity was smaller than that of the initial increase. Percent GG activity was significantly lower than both percent IIM activity and percent minute ventilation during the decline and plateau phases. There were no significant differences in ventilatory and EMG responses between the normal subjects and the patients with OSA. We conclude that, during wakefulness, upper airway muscle activity declined to a greater extent than inspiratory pump muscle activity during sustained hypoxia.
We developed a new portable sleep monitoring system and studied the prevalence of sleep apnea syndrome among Japanese industrial workers. This device assessed three kinds of parameters: nasal airflow, tracheal sound and electrocardiogram (ECG), and digitally stored the clock time of the onset of apnea, apnea duration and R-R intervals by a built-in microcomputer. After monitoring, the portable sleep monitor was connected to a host computer, and apneic episodes, the so-called 'apnea index' as apneic episodes corrected by measuring time ('AI') and R-R intervals were analyzed. In 170 inpatients referred to our sleep clinic, sleep monitoring by this device was performed simultaneously with all-night polysomnography, and the sensitivity and specificity of this device was determined under different criteria of the apnea index (AI) (AI > 5, 10, 15 and 20 episodes/h) by polysomnography. In all AI criteria, the sensitivity was more than 90%, and the specificity was also reasonably high. Using this system, successive 2-night home sleep monitoring was performed on 168 healthy workers in one Japanese industrial company, and 159 people (140 males; 19 females) who had successful monitoring were analyzed. The percentage of persons who had 'AI' of more than 10 episodes/h was 7.5%. There were no significant correlations between 'AI' and age, body weight or scores estimated by sleep questionnaires. These results suggest that even in people who are seemingly healthy significant apneic episodes could be detected by the portable home sleep monitoring system. This system may therefore be useful in evaluating the occurrence of sleep apnea syndrome in general populations.
Upper airway dilating muscle activity increases during apneic episodes in patients with obstructive sleep apnea (OSA). To elucidate the relative contribution of chemical and nonchemical stimuli to augmentation of the upper airway dilating muscle, we measured the response of genioglossus muscle (GG) and inspiratory intercostal muscle (IIM) activities to obstructive apnea during non-REM sleep and compared them with the response to progressive hypoxia and hypercapnia during awake periods in seven male patients with OSA. GG EMG was measured with a wire electrode inserted percutaneously, and IIM EMG was measured with surface electrodes placed in the second intercostal space parasternally. Responses to hypoxia and to hypercapnia were assessed by rebreathing methods in the supine position while awake. Following these measurements, a sleep study was conducted with the EMG electrodes placed in the same locations. The relationship between GG and IIM activities during the cycle of apnea and postapneic ventilation in non-REM sleep was quasi-linear, and the slope of the regression line was significantly greater than those during progressive hypoxia and progressive hypercapnia. The amplitude of GG activity at 70% of maximum IIM activities in the hypoxic test was 140 +/- 20% (mean +/- SEM) during non-REM sleep, which was also significantly greater than that during hypoxia (51 +/- 10%) and that during hypercapnia (59 +/- 15%). These results suggest that nonchemical factors contribute considerably to augmentation of GG activity during obstructive apneic episodes. The nonchemical stimuli may arise from mechanoreceptors activated by upper airway obstruction and behavioral factors associated with change in sleep states.
Peripheral blood mononuclear cells (PBMC) and serum were obtained, on two occasions, from 15 asthmatic patients who required oral glucocorticoid therapy for moderate to severe disease exacerbations. Samples were obtained immediately before commencement of oral glucocorticoids (Day 1) and again after 7 days of treatment (Day 7), when lung function had significantly improved. Samples were also isolated on two occasions 7 days apart from a group of seven untreated volunteers. Expression of CD25, human lymphocyte antigen (HLA-)DR, CD45RA, and CD45RO on CD4 and CD8 T lymphocytes was measured by flow cytometry, and serum concentrations of interleukin-5 (IL-5) were measured using an enzyme-linked immunosorbent assay technique. On Day 1 the asthmatic patients showed significantly higher percentages, as compared with the control subjects of CD4 T lymphocytes expressing the markers CD25, HLA-DR, and CD45RO and significantly lower percentages of CD4 T cells expressing CD45RA. After glucocorticoid therapy, the percentages of CD4 T cells expressing CD25, HLA-DR, and CD45RO were significantly reduced in the asthmatic patients, and the percentages of those expressing CD45RA significantly increased so that by Day 7 expression of all four markers was no longer significantly different from that of the control subjects. By contrast, the percentages of CD8 T cells expressing HLA-DR, CD45RA, and CD45RO in the PBMC of the asthmatic patients on Day 1 were not significantly different from those in control subjects, whereas the percentages of CD25 expressing CD8 T cells were only marginally elevated. Glucocorticoid therapy resulted in no significant change in the expression of all four markers on CD T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
This report describes a rare clinical course of a young Japanese woman with Takayasu's arteritis and a review of the literature. Her first symptom was angina pectoris due to isolated left coronary ostial stenosis, which was relieved by aortocoronary bypass grafting surgery using a saphenous vein graft. At that time, the C-reactive protein was negative and the histopathologic findings of the specimens of the aorta could not confirm aortitis. Although she was free from any cardiovascular symptoms for about fifteen years, syncopal attacks occurred owing to severe stenosis of the major branches of the aortic arch revealed by intravenous digital subtraction arteriograms. Thus, Takayasu's arteritis could be a cause of coronary ostial stenosis in young women even if the inflammatory findings are negative and the major branches of the aortic arch are not involved at operation. In addition, revascularization using internal thoracic arteries might possess a potential risk of coronary insufficiency due to a later involvement of these proximal arteries.
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This report describes a 69-year-old Japanese woman with bilateral forearm thrombophlebitis that developed soon after transvenous permanent pacemaker insertion. Intravenous administration of urokinase and heparin rapidly resolved fever, painful forearm swelling and inflammatory findings. Digital subtraction venograms revealed a brachiocephalic vein thrombosis. A ten-month treatment with warfarin and ticlopidine resulted in the complete restoration of venous flow. Although thrombophlebitis associated with transvenous permanent pacemaker insertion has a relatively low incidence (0.3%), prompt diagnosis and treatment with anticoagulant and/or thrombolytic agents are important for the late clinical outcome in cases with deep venous thrombosis.
The purpose of this study was to examine the effect of ramp slope during progressive exercise test on the intracellular pH threshold (pHT) of working muscle. To attain the purpose, we measured intracellular pH of wrist flexor by 31P-MRS during four kinds of ramp wrist flexion. Five Japanese males participated as subjects. They performed wrist flexion in a bore of MRS system, with ramp increments of 0.14, 0.20, 0.26 and 0.31 W/min till exhaustion. Intracellular pH of wrist flexor muscle was estimated from a chemical shift between inorganic phosphate (Pi) and phosphocreatine (PCr) on a 31P-MR spectra. Pi-to-PCr ratio (Pi/PCr) as an index of oxidative phosphorylation potential was also calculated. pH and Pi/PCr were obtained as minute-by-minute data throughout the exercise. pHT was determined as a work rate (W) just before that at which the intracellular acidosis (acidemia) occurred. Although work endurance was shortened significantly, achieved maximal work rate (WRmax) was increased with an increase in ramp slope. pHT both in the unit of W and %WRmax was not affected significantly by the ramp slope. On the other hand, Pi/PCr at pHT decreased with an increase in ramp slope, significantly. These results suggested that intracellular homeostasis with reference to acid-base equilibrium was not dependent on oxidative phosphorylation status, but a work output of the muscle.
Threshold of decline in intracellular pH of muscle (pHT) during incremental wrist flexion was studied by 31P-MRS, under two levels of occlusions in which the cuff of the upper arm was inflated to systolic (ES) and diastolic blood pressure (ED), and no occlusion (E). To observe the effect of occlusion per se, intracellular pH at rest under the same two levels of occlusion was measured. Additionally, NIRS was applied to monitor the oxygenation and blood volume of the tissue during the same experimental protocol as the 31P-MRS study. Ten healthy Japanese males participated as subjects in the 31P-MRS study, and three of them in the NIRS study. They performed wrist flexion in incremental loads of 0.14 W/min ramp until voluntary exhaustion. 31P-MRS and NIRS were obtained from wrist flexor muscles. Change in intracellular pH (pH) during wrist flexion showed a threshold behavior even in ischemic conditions, although pH did not decrease at rest under the same two levels of occlusion. This finding indicated that decrease in pH under occlusion is also resulted from exercise induced lactic acidosis. Obtained pHT in ES was smaller than in ED and E significantly, and there was no significant difference between pHT in ED and that in E. From the results of NIRS study, it was confirmed that only venous outflow but not arterial inflow was restricted under an occlusion at a pressure of diastolic blood pressure, but both under an occlusion at a pressure of systolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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This study was performed to elucidate whether endometriotic lesions can affect peripheral blood lymphocyte-subsets. Changes of lymphocyte-subsets of normal healthy women and patients with uterine myoma or endometriosis before and after operation were also examined by using two-color assay methods. The percentage and absolute number of CD57+CD16+ cells [moderately differentiated natural killer (NK) cells] of NK cell subsets in peripheral blood from patients with endometriosis were significantly lower than values from normal healthy women and patients with uterine myoma, while there was no difference in CD4+ and CD8+ lymphocyte-subsets between normal healthy women and patients with uterine myoma or endometriosis. In patients with endometriosis the percentage and absolute number of CD8+CD11+ cells (suppressor T-cells) was significantly increased after operation, while those in patients with urine myoma did not change. On the other hand, resection of endometriotic lesions resulted in a significant decrease of the percentage of CD57+CD16- cells (immature NK cells) and a significant increase of not only the percentage but also the absolute number of CD57+CD16+ cells (moderately differentiated NK cells), suggesting that existence of endometriotic lesions disturbs differentiation of the NK cells. Furthermore, suppressor inducer T-cells as shown by measuring CD4+2H4+ and CD4+4B4- cells were significantly increased after operation of endometriosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Three hairpin ribozymes were designed to cleave Escherichia coli beta-glucuronidase (GUS) mRNA at a target site. Two of the designed ribozymes (HG10L and HG10L2) had long substrate binding sites and the other (HG10) had short substrate binding site. All three ribozymes cleaved the substrate, and HG10L and HG10L2 cleaved it efficiently. However, HG10 had very low activity. Effect of length of substrate binding site of the ribozyme will be discussed.