Inositol phospholipid turnover and protein phosphorylation in secretory responses.
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Biomedical subjects
Publications and source records attributed to M Go.
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Using a commercial pulsed Doppler (PD) system we measured common carotid artery (CCA) flow velocities in 19 healthy and 6 stable preterm infants and computed volume flow rates based on the time-averaged flow velocities and vessel diameter. The mean (+/- SEM) time-averaged CCA velocities in the term and preterm infants were 33.04 +/- 3.0 and 23.3 +/- 1.3 cm.s-1, respectively. The total flow volume was significantly higher in the term as opposed to preterm infants: 126 +/- 11.2 vs. 55.6 +/- 7.7 ml/min (p less than 0.01). The body-weight-normalized flow volume, however, was not statistically significantly different between the two groups of infants. Several technical and practical limitations still exist to compute cerebral blood flow (CBF) volume accurately. In a puppy model we measured the CCA flow volume by electromagnetic flowmeter technique, and the PD device simultaneously. The correlation coefficient between 32 pairs of measurements was 0.93 (p less than 0.005). We conclude that commercial PD devices provide accurate velocity data, and under experimental conditions, the computed volume flow rates are accurate. Although in clinical situations reasonably accurate CBF values can be estimated, refinements in technology are needed to adopt this method as a possible means of measuring CBF at the bedside.
We previously reported that immunoreactive corticotropin-releasing hormone (CRH) is present in human placenta and third trimester maternal plasma, and that such material is very similar to rat CRH and the predicted structure of human CRH. We suggested that maternal plasma immunoreactive CRH may be of placental origin. To further investigate this possibility, we measured plasma immunoreactive CRH in women during pregnancy, labor, and delivery and 1 and 2 h postpartum, and in nonpregnant women. Umbilical cord plasma and placental CRH concentrations were also measured. In the first trimester of pregnancy, the mean maternal plasma level was 5.9 +/- 1.0 pg (+/- SEM)/ml (n = 24), not significantly different from that in 10 nonpregnant women (5.8 +/- 0.8 pg/ml). Plasma CRH concentrations progressively increased during pregnancy (second trimester, 35.4 +/- 5.9 pg/ml (n = 39); early third trimester (28-34 weeks), 263 +/- 41 pg/ml (n = 14); late third trimester (35-40 weeks), 800 +/- 163 pg/ml (n = 20)]. There was a significant correlation between maternal plasma CRH levels and weeks of pregnancy. Plasma CRH concentrations were further elevated (2215 +/- 329 pg/ml; n = 9). During early labor, peaked at delivery (4409 +/- 591 pg/ml; n = 28), and declined rapidly after delivery [1 h postpartum, 1042 +/- (353 pg/ml (n = 13); 2 h postpartum, 346 +/- 91 pg/ml (n = 13)]. There was a significant correlation (r = 0.562; P less than 0.01) between matched maternal plasma and placental CRH concentrations. The mean umbilical cord plasma CRH level (50.6 +/- 6.1 pg/ml; n = 28) was much lower than that in the mother at the time of delivery. Umbilical venous plasma CRH levels were significantly greater than those in simultaneously obtained umbilical arterial plasma (70.8 +/- 11.3 and 41.8 +/- 4.9 pg/ml, respectively; n = 11). There was a significant correlation (r = 0.384; P less than 0.05) between maternal and fetal CRH concentrations. Gel filtration of plasma obtained from women during the third trimester, at delivery, and early postpartum and placental extracts revealed two major peaks of immunoreactive CRH: a high mol wt peak and one at the elution position of rat CRH. In contrast, only rat CRH-sized material was detected in plasma from nonpregnant women and umbilical cord plasma. Maternal plasma immunoreactive CRH-sized material stimulated ACTH release from anterior pituitary tissue in a dose-dependent manner and was equipotent with rat CRH.(ABSTRACT TRUNCATED AT 400 WORDS)
Immunoreactive CRH concentrations were determined in human plasma using an immunoaffinity chromatographic extraction procedure and sensitive RIA. Immunoreactive CRH was detectable in the plasma of all normal subjects (mean +/- SD, 6.2 +/- 2.4 pg/mL; n = 15). Basal (0800-1000 h) plasma immunoreactive CRH levels were significantly lower in patients with Cushing's syndrome due to adrenal (2.8 +/- 1.1 pg/mL; n = 4) or pituitary adenomas (2.9 +/- 0.8 pg/mL; n = 5), in patients with hypothalamic hypopituitarism (3.2 +/- 0.9 pg/mL; n = 5), and in glucocorticoid-treated patients (3.9 +/- 1.9 pg/mL, n = 8). Basal plasma CRH levels were also low in patients with acromegaly (2.8 +/- 0.8 pg/mL; n = 14) and insulin-treated diabetic patients whose pituitary-adrenal function was normal (3.6 +/- 1.0 pg/mL; n = 12). In normal subjects plasma CRH levels increased after insulin-induced hypoglycemia; this response was abolished by the prior administration of dexamethasone. In contrast, basal plasma CRH levels were not affected by prior administration of metyrapone or dexamethasone. No evidence for diurnal variation in plasma immunoreactive CRH was found in normal subjects. In addition, in normal subjects oral glucose administration elicited a significant increase in plasma CRH (basal, 7.3 +/- 0.9 pg/mL; peak 30 min after glucose, 16.7 +/- 5.8 pg/mL; n = 5; P less than 0.05) without concomitant changes in ACTH. Gel filtration of extracts of pooled plasma from normal subjects revealed a major component of immunoreactive CRH in the position of synthetic rat CRH. Immunoreactive CRH-sized material had the same retention time as authentic rat CRH in a reverse phase high pressure liquid chromatography system. The content of immunoreactive CRH in human placenta, pancreas, and adrenal gland was much larger than that in hypothalamus. These findings suggest that immunoreactive CRH is present in peripheral plasma; the increase in plasma immunoreactive CRH after insulin-induced hypoglycemia may reflect stimulation of hypothalamic CRH release; the increase in plasma immunoreactive CRH after glucose administration may reflect extrahypothalamic CRH release; and the lack of diurnal variation in plasma immunoreactive CRH together with the lack of suppression of CRH by dexamethasone suggest that basal plasma CRH is of extrahypothalamic origin.
The effects of rat corticotropin-releasing hormone (CRH) and of synthetic peptide histidine methionine (PHM) on ACTH release were studied in vivo in humans. PHM alone did not alter the basal plasma ACTH or cortisol levels, but it strongly potentiated CRH-induced ACTH secretion. These results, together with our previous observation that PHM immunoreactivity is present in human hypothalamus and pituitary stalk, suggest that PHM may play a physiological role in the regulation of ACTH secretion in humans.
Two cases of carcinoma in a diverticulum of the bladder were experienced. The first case was of a 50-year-old male who presented in February, 1981, complaining of asymptomatic microhematuria. The excretory urogram revealed a diverticulum in the left lateral aspect of the bladder which was causing shift of the lower ureter to the median side. The cytology report of voided urine was class III. Diverticulectomy was performed and pathologic findings was a transitional cell carcinoma, grade 1, stage 0. The patient has been free of recurrence for the past 54 months. The second case was of a 67-year-old male with the chief complaint of pollakiuria. Non-papillary tumor in a diverticulum of the bladder was found by cystoscopy and computed tomography. Tumor biopsy and urinary diversion by ileal conduit were performed in the usual manner. The pathologic finding was transitional cell carcinoma of grade 11 malignancy. The patient died of intestinal obstruction on January, 19, 1984, about 15 months after the surgery. The 117 cases of carcinoma in a diverticulum of the bladder we found in the Japanese literature are reviewed briefly.
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Fifty-eight of the 44,698 patients seen at our Department, between 1972 and 1984 had a testicular tumor. The incidence rate was 0.13%. The mean age of these 58 cases was 28.6 years and two peak distributions, one in the 0 to 5 year and another in 26 to 30 year age group were observed. Among them, 54 patients (93.1%) had chief complaints of painless testicular swelling at initial examination. The vast majority of them had unilateral tumors; 28 in the right and 29 in the left. Only one patient had bilateral seminomas. Histologically, 30 of them (51.7%) were seminoma, 8 were embryonal carcinoma (13.8%), 2 were teratoma (3.5%) and the remaining 18 had tumors of double or multiple histological type. Most of the seminomas were treated by a combination of high orchiectomy and radiotherapy, and chemotherapy was done mainly for non-seminomatous cases. The 5-year survival rate calculated by the Kaplan-Meier method was 100% for patients with low stage (I, II) seminomas and 62% for those with non-seminomatous tumors.
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Protein kinase C was purified from rat brain cytosol by using a high performance liquid chromatography (HPLC), Pharmacia FPLC system. This procedure employed a column chromatography on DE-52, followed by three steps of HPLC procedures with threonine-Sepharose (prepared as described in this report), TSK gel Phenyl-5PW (Toyo Soda), and TSK gel G3000SW (Toyo Soda) columns. Starting from about 30 g of rat brain, approximately 200 micrograms of pure enzyme was obtained. The procedure was very simple and highly reproducible. The enzyme thus obtained was nearly pure by silver staining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the presence of 10% (w/v) glycerol and 0.05% (w/v) Triton X-100, the enzyme could be stored at -80 degrees C for several months.
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A computer-derived treadmill exercise score that quantifies the electrocardiographic response to exercise has been reported to have a high sensitivity (87 per cent) and specificity (92 per cent) in patients with a high prevalence of coronary artery disease. To test its accuracy in young, asymptomatic men with a low prevalence of coronary artery disease, we evaluated the responses of 377 military officers (mean age, 36.6 years) by two independent methods. According to standard electrocardiographic criteria, 45 of the subjects (12 per cent) had positive tests, whereas the treadmill exercise score indicated that only 3 (less than 1 per cent) had positive tests. Since two of these three had left ventricular hypertrophy and met only the criteria for the latter without associated coronary artery disease, the treadmill exercise score predicted that only 1 of 377 subjects would have clinically important coronary artery disease. Coronary arteriography, performed in 10 persons with the most positive scores on standard treadmill tests and the highest scores for risk factors, showed that nine subjects did not have coronary artery disease and that one had single-vessel disease (the same subject who the treadmill score predicted would have mild disease). The treadmill exercise score appears to improve the diagnostic specificity of exercise electrocardiography and may be more useful than values on standard stress tests in screening asymptomatic populations for coronary artery disease.
Does 2 mm of ST depression induced by exercise have the same clinical significance in a patient with a 30-mm R wave as a patient with a 10-mm R wave in the same monitored lead? To answer this question the exercise responses of 85 patients were compared by 2 quantitative methods of assessing myocardial ischemia. A computer-derived treadmill exercise score, based largely on the characteristics of exercise-induced ST-segment depression, was compared with a thallium exercise score. Both scores correlated well over a wide range of values (r = 0.71, p less than 0.001). Then, the treadmill exercise score was corrected (by adjusting the magnitude of the ST depression to a standardized R-wave amplitude of 12 mm in V5 and 8 mm in aVF) to determine if this would improve its correlation with the thallium exercise score. The patients were separated into 2 groups by R-wave amplitude: 53 had an RV5 of 9 to 17 mm and 32 had an RV5 less than 9 or greater than 17 mm. Correction of the treadmill exercise score for R-wave amplitude did not change the slope and intercepts of the regression line for patients with an RV5 amplitude of 9 to 17 mm, but did for those with an RV5 amplitude less than 9 or greater than 17 mm. In this latter group, R-wave correction changed the regression line from one that differed significantly from that of patients with less extreme RV5 voltage to one that was indistinguishable from it. Correction of the treadmill exercise score also increased the correlation coefficient from 0.54 to 0.68 in this group.(ABSTRACT TRUNCATED AT 250 WORDS)
Exon-intron structures of eukaryotic genes were examined closely in their relation to primary and tertiary structures of the proteins they encode. Specific attention was given to the introns of genes encoding proteins having no repeats in their amino acid sequences. such introns have been shown to be located at sites corresponding to inter-domain or inter-module junctions of proteins identified in their three dimensional structures. "Modules," compact structural units in globular domains of proteins, are identified by drawing a distance map. Intron positions are found to correspond to intermodule junctions in various proteins whose X-ray crystallographic data are available: the globin family, CEWL, ovomucoid, cytochrome c, ADH, and trypsin-like serine proteinases. The good correspondence between intron positions and intermodule junctions excludes a mechanism of random insertion of introns, because the probability of intron insertion at each intermodule junction is extraordinarily small. Intron positions have been very stable and well conserved during evolution. However, at some inter-module junctions no introns are found. Modules in small proteins having no core modules buried in their interior have a character suitable for recruitment through their assembly into a stable domain; one side of them is rich in hydrophobic residues and the other in hydrophilic residues. Functionally important residues are scattered on different modules in the proteins examined. Based on these observations, the role of modules in the precellular period was conjectured: some of them might be functionally active by themselves but most modules might be only segments who could function as an active protein only in an assembly. The origin of introns might be traced back prior to the divergence of prokaryotes and eukaryotes.
As a prelude to clinical trials with a bovine surfactant (surfactant TA), in human infants with hyaline membrane disease, pulmonary and hemodynamic changes following its instillation in premature baboons were investigated. Baboons, delivered by cesarean section at 141 +/- 3.5 days (mean +/- SD, 77% gestation), were provided with intensive care. At 2 hours of age in one group (n = 10), 100 mg/kg of surfactant TA (reconstituted bovine surfactant, Tokyo Tanabe Co., Tokyo) was instilled into the lungs. Sequential measurements and monitoring of pulmonary and hemodynamic variables were carried out in these ten baboons and in a control group of five baboons for 16 hours, at which time the experiments were electively terminated. At birth, the pulmonary compliance, findings of chest radiographs, ratio of arterial PO2 to alveolar PO2, and respirator variables needed to maintain normal blood gas and acid base status were identical in both groups and indicative of severe hyaline membrane disease. Following surfactant instillation, the treated group demonstrated a rapid increase in PO2 with significantly improved ratio of arterial PO2 to alveolar PO2 (from a mean +/- SD pretreatment value of 0.21 +/- 0.11 to 0.45 +/- 0.11 by 16 hours). Pulmonary compliance improved similarly (from pretreatment value of 0.18 +/- 0.06 mL/cm H2O/kg to 0.27 +/- 0.09 mL/cm H2O/kg). Significant reduction in respirator support variables could be achieved in all treated animals; however, in the control animals, the pulmonary status worsened as evidenced by increasing mean airway pressure and respirator variables to keep normal blood gas and acid base status, thus worsening compliance. At autopsy, pulmonary pressure-volume curves were significantly different with large hysteresis obtained in the surfactant-treated group. Although no deleterious effect on hemodynamics was noted in surfactant TA-treated animals, a large patent ductus arteriosus was demonstrated by aortography. Increased lung blood flow, probably due to a large patent ductus arteriosus flow, was demonstrated by radiolabeled microsphere technique. The physiologic significance and clinical relevance of these findings in premature baboons treated with surfactant TA are discussed.
The efficacy of therapy with diltiazem, 360 mg/day, was studied in 11 men with chronic, stable angina pectoris. An initial dose-titration schedule in which diltiazem was increased weekly from placebo to 120, 240 and 360 mg/day (Period I) was followed by a randomized, double-blind, 1-month crossover trial of placebo vs diltiazem at 360 mg/day (Period II). A computer-assisted treadmill exercise test was performed at the end of each dose and each 2-week crossover period. Diltiazem at 360 mg/day, compared with placebo (Period II), significantly improved exercise performance. Exercise duration to onset of chest pain increased 40% from 5.3 +/- 2.1 to 7.4 +/- 2.7 minutes (p less than 0.01). Time to reach 1 mm of ST-segment depression increased 33%, from 5.1 +/- 2.0 to 6.8 +/- 1.8 minutes (p less than 0.01). Total exercise duration increased 16%, from 7.5 +/- 2.0 to 8.7 +/- 2.0 minutes (p less than 0.005). A computer-derived quantitative treadmill exercise score improved 27%, from -13.1 +/- 9.4 to -9.5 +/- 7.6 units (p less than 0.005), and the ST-segment depression at peak exercise improved from -1.9 +/- 1.1 to -1.6 +/- 1.2 mm (p less than 0.05). Progressive improvement in these variables was seen during the single-blind dose-titration period between 120 and 240 mg/day and between 240 and 360 mg/day (Period I). Baseline heart rate (HR) and diastolic blood pressure (BP) in the supine and upright position were significantly lower with diltiazem than with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
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