[Module structure of hemoglobin].
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Biomedical subjects
Publications and source records attributed to M Go.
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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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The short- and long-term effects of various Nitro-Dur formulations on performance and hemodynamics were studied in 15 men with stable angina pectoris who also had a positive treadmill exercise test. A treadmill exercise score (TES) was used that quantified the "ischemic" ST segment response to exercise. The score incorporated information that reflected the rapidity of evolution of ST segment depression during exercise and the time required for it to resolve after cessation of exercise. In early tests (n = 10) Nitro-Dur improved both the TES (by 31%: p less than 0.0001) and the time required for 1 mm ST segment depression (by 33%: p less than 0.0001). At all dosage levels, Nitro-Dur also decreased resting systolic blood pressure and increased resting heart rate. No dose-response patterns emerged. Changes in TES and time to ST segment depression were greater with sublingual nitroglycerin than they were with Nitro-Dur. In tests conducted after prolonged dosage (n = 5), the effects of Nitro-Dur on blood pressure and heart rate became attenuated at weeks 2 and 4, although cardiac responsiveness was preserved, as reflected in the increased time required before the occurrence of 1 mm ST segment depression. The latter effect was also observed with sublingual nitroglycerin. The clinical relevance of these data to the design of individual patient therapy is discussed.
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By the application of the same algorithm for finding compact structural units encoded by exons as applied previously to hemoglobin, five units, M1-M5, were identified in chicken egg white lysozyme. They consist of residues 1-30, 31-55, 56-84, 85-108, and 109-129, respectively. I call these compact structural units "modules." As in hemoglobin, modules thus identified correspond well to exons--i.e., modules M1, M2 plus M3, M4, and M5 correspond to exons 1, 2, 3, and 4 of the lysozyme gene, respectively. Localization of the catalytic sites glutamic acid-35 and aspartic acid-52 on the module M2 suggests that this module might have worked as a functional unit in a primitive lysozyme. The good correspondence between exons and modules reinforces the idea of "proteins in pieces," which was derived from the fact of "genes in pieces." The evolutionary origin of the introns in globins and lysozyme is discussed.
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The antitussive and respiratory stimulant properties of N-(2'-ethylpyrrolidino)diphenylacetamide hydrochloride (F 1459) in animals are reported. In the mechanical stimulation of the trachea in guinea pigs and after intraperitoneal administration of the product, F 1459 showed a better antitussive action as compared to oxeladin, zipeprol, codeine and clobutinol. Low intraduodenal doses of F 1459 also reduced in cats the cough induced by the electrical stimulation of the superior laryngeal nerve. In anesthetized dogs whose respiratory functions had been depressed by morphine, F 1459 significantly increased the volume inspired per minute, an effect not due to any uncoupling effect on oxidative phosphorylation. F 1459 has local anesthetic and broncholytic properties that may play a role in the mechanism of its antitussive action. Contrarily to codeine, the test compound did not induce a decrease in the intestinal transit.
The discovery of intervening sequences (introns) in DNA led Gilbert and Tonegawa to suggest that a new protein could have been produced by bringing together certain segments of pre-existing ones. However, Blake argued that if DNA was so organized that coding sequences (exons) correspond to structural as well as functional units of proteins, then combinations would be much more likely to yield a stable globular conformation through being 'sums of parts'. In immunoglobulin heavy chain, four separate exons encode four different units, all with distinct functions and three of which have clear domain structures. However, in haemoglobin, which has no obvious domain structure, no clear conformational characteristics have so far been recognized for the segments encoded by exons. From a close inspection of their conformations by drawing various stereodiagrams and the Calpha-Calpha distance map, I now propose a conformational characterization of the segments as structural units.