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1.
Am J Physiol Cell Physiol ; 279(1): C257-65, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10898737

ABSTRACT

We tested the hypothesis that the beta-myosin heavy chain (beta-MHC) 3'-untranslated region (UTR) mediates decreased protein expression after tenotomy of the rat soleus. We also tested the hypothesis that decreased protein expression is the result of RNA-protein interactions within the 3'-UTR. beta-MHC was chosen for study because of its critical role in the function of postural muscles such as soleus. Adult rat soleus muscles were directly injected with luciferase (LUC) reporter constructs containing either the beta-MHC or SV40 3'-UTR. After 48 h of tenotomy, there was no significant effect on LUC expression in the SV40 3'-UTR group. In the beta-MHC 3'-UTR group, LUC expression was 37.3 +/- 4% (n = 5, P = 0.03) of that in sham controls. Gel mobility shift assays showed that a protein factor specifically interacts with the beta-MHC 3'-UTR and that tenotomy significantly increases the level of this interaction (25 +/- 7%, n = 5, P = 0.02). Thus the beta-MHC 3'-UTR is directly involved in decreased protein expression that is probably due to increased RNA-protein binding within the UTR.


Subject(s)
3' Untranslated Regions/physiology , Genes, Reporter/physiology , Muscle Proteins/biosynthesis , Myosin Heavy Chains/genetics , RNA, Messenger/physiology , Tendons/physiology , 3' Untranslated Regions/genetics , Animals , Antisense Elements (Genetics)/genetics , Base Sequence/genetics , Female , Gene Expression , Luciferases/metabolism , Molecular Sequence Data , Molecular Structure , Muscle Proteins/metabolism , Muscle, Skeletal/metabolism , Muscular Atrophy/metabolism , Protein Isoforms/genetics , Rats , Rats, Sprague-Dawley
2.
J Appl Physiol (1985) ; 88(3): 1127-32, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10710412

ABSTRACT

What determines the shape, size, and force output of cardiac and skeletal muscle? Chicago architect Louis Sullivan (1856-1924), father of the skyscraper, observed that "form follows function." This is as true for the structural elements of a striated muscle cell as it is for the architectural features of a building. Function is a critical evolutionary determinant, not form. To survive, the animal has evolved muscles with the capacity for dynamic responses to altered functional demand. For example, work against an increased load leads to increased mass and cross-sectional area (hypertrophy), which is directly proportional to an increased potential for force production. Thus a cell has the capacity to alter its shape as well as its volume in response to a need for altered force production. Muscle function relies primarily on an organized assembly of contractile and other sarcomeric proteins. From analysis of homogenized cells and molecular and biochemical assays, we have learned about transcription, translation, and posttranslational processes that underlie protein synthesis but still have done little in addressing the important questions of shape or regional cell growth. Skeletal muscles only grow in length as the bones grow; therefore, most studies of adult hypertrophy really only involve increased cross-sectional area. The heart chamber, however, can extend in both longitudinal and transverse directions, and cardiac cells can grow in length and width. We know little about the regulation of these directional processes that appear as a cell gets larger with hypertrophy or smaller with atrophy. This review gives a brief overview of the regulation of cell shape and the composition and aggregation of contractile proteins into filaments, the sarcomere, and myofibrils. We examine how mechanical activity regulates the turnover and exchange of contraction proteins. Finally, we suggest what kinds of experiments are needed to answer these fundamental questions about the regulation of muscle cell shape.


Subject(s)
Heart/physiology , Muscle, Skeletal/cytology , Muscle, Skeletal/physiology , Myocardium/cytology , Adult , Animals , Cell Size , Humans , Muscle Proteins/metabolism , Myofibrils/ultrastructure , Sarcomeres/ultrastructure
3.
Am Heart J ; 104(2 Pt 1): 185-93, 1982 Aug.
Article in English | MEDLINE | ID: mdl-6213141

ABSTRACT

During the past 5 years, we have seen six patients who met inclusion criteria of exertional palpitations, reproducible treadmill (TM) provocable ventricular tachycardia (VT), and performance of electrophysiologic (EP) studies including isoproterenol (ISO) infusion. There were five males and one female, aged 15 to 55 years (mean +/- SD, 31 +/- 18 years). Three patients were trained athletes, two patients had mitral valve prolapse, three had enlarged right ventricular (RV) volumes (all trained athletes), and two had no evidence of organic heart disease. TM testing in all patients demonstrated reproducible exercise-provocable VT of at least 20 beats' duration. TM VT was characterized by left bundle branch block pattern ORS morphology and rates of 150 to 230 bpm (186 +/- 30 bpm). EP did not reproduce VT in five of six patients while ISO at a dose of 2 to 4 micrograms/min (2.5 +/- 0.8 micrograms/min) reproduced VT in all patients. ISO VT was characterized by QRS morphology identical to TM VT and rates of 165 to 230 bpm (191 +/- 26 bpm). Endocardial mapping of ISO VT revealed earliest activity in RV outflow tract. Serial TM testing revealed suppression of TM VT in all six patients on propranolol therapy. Responses to class I drugs were variable and less successful. In summary, we describe a group of patients with common clinical, ECG, and electrophysiologic features who may share a common pathophysiology of VT. Possible mechanisms are discussed.


Subject(s)
Physical Exertion , Tachycardia/etiology , Adolescent , Adult , Anti-Arrhythmia Agents/therapeutic use , Bundle-Branch Block/etiology , Bundle-Branch Block/physiopathology , Cardiomegaly/physiopathology , Electric Stimulation , Electrocardiography , Electrophysiology , Female , Heart Ventricles/physiopathology , Humans , Infusions, Parenteral , Isoproterenol/adverse effects , Male , Middle Aged , Mitral Valve Prolapse/physiopathology , Monitoring, Physiologic , Propranolol/therapeutic use , Tachycardia/drug therapy , Tachycardia/physiopathology
4.
Chest ; 82(1): 19-24, 1982 Jul.
Article in English | MEDLINE | ID: mdl-7083929

ABSTRACT

Twenty-four hour ambulatory ECG recordings were performed on 20 male long-distance runners, aged 19 to 28 years, during normal activities other than running. Average, maximum, and minimum waking heart rates, respectively, ranged from 58 to 108 (mean +/- SD, 73 +/- 15), 90 to 164 (120 +/- 19), and 34 to 53 (43 +/- 5) beats/min. Longest waking sinus pauses ranged from 1.35 to 2.55 (1.7 +/- 0.3) seconds. Average, maximum, and minimum sleeping heart rates, respectively, ranged from 38 to 58 (47 +/- 6), 69 to 114 (83 +/- 14), and 31 to 43 (36 +/- 3) beats/min. Longest sleeping sinus pauses ranged from 1.60 to 2.81 (2.0 +/- 0.3) seconds. All 20 runners had atrial premature beats, but only one (5 percent) had more than 100/24 hours. Fourteen runners (70 percent) had ventricular premature beats, but only two (10 percent) had more than 50/24 hours, and none had ventricular couplets or ventricular tachycardia. Eight runners (40 percent) had one or more episodes of type 1 second-degree atrioventricular (A-V) block. Compared with untrained males of similar age, the runners had slower heart rates (by approximately 10 beats/min), longer sinus pauses, and a higher prevalence of A-V block. Runners and untrained males did not differ with respect to prevalence of ventricular premature beats, R on T phenomenon, ventricular couplets, or ventricular tachycardia.


Subject(s)
Electrocardiography , Running , Adult , Arrhythmias, Cardiac/epidemiology , Arrhythmias, Cardiac/etiology , Heart Block/epidemiology , Heart Block/etiology , Heart Rate , Humans , Male , Physical Fitness
7.
Am Heart J ; 90(4): 463-7, 1975 Oct.
Article in English | MEDLINE | ID: mdl-1172368

ABSTRACT

Six patients in functional class II and 11 in functional class III underwent graded treadmill exercise, with severe fatigue as their limiting symptom. During exercise, none of the patients developed chest pain, or significant arrhythmia. Our data suggest that at a treadmill workload of 2 mph and 7 per cent slope, with an oxygen consumption four times that at rest, measurement of the pulmonary arterial oxygen saturation permits clear separation of functional class II from functional class III. Although there was a significant difference in the heart rate response, mean pulmonary arterial pressure, and percentage change in pulmonary arterial end-diastolic pressure, considerable overlap occurred. The use of pulmonary arterial oxygen saturation may prove to be of value in instances in which the functional cardiac status is not reasonably clear from the clinical interview or routine exercise testing. It requires less than maximal effort on the part of the patient, and provides an objective end point to distinguish between two important groups of patients.


Subject(s)
Exercise Test , Oxygen/blood , Pulmonary Artery/physiology , Adult , Blood Pressure , Cardiomyopathy, Hypertrophic/diagnosis , Female , Heart Diseases/diagnosis , Heart Rate , Humans , Male , Middle Aged , Oxygen Consumption , Pulmonary Artery/physiopathology , Rheumatic Heart Disease/diagnosis
8.
Aviat Space Environ Med ; 46(4 Sec 2): 500-13, 1975 Apr.
Article in English | MEDLINE | ID: mdl-1156266

ABSTRACT

To detect the passage of cosmic ray particles through the heads of the pocket mice during the Apollo XVII flight, a "monitor" (dosimeter) composed of plastics was prepared and implanted under the scalp. The monitor was mounted on a platform, the undersurface of which fitted the contour of the skull. Numerous tests were run to assure that the presence of the monitor assembly beneath the scalp would be compatible with the well-being of the mice and that the capacity of the monitor to detect the traversal of cosmic ray particles would be preserved over the several weeks during which it would remain under the scalp.


Subject(s)
Cosmic Radiation , Radiation Effects , Radiation Monitoring/instrumentation , Space Flight , Animals , Mice , Scalp , United States
9.
Aviat Space Environ Med ; 46(4 Sec 2): 514-20, 1975 Apr.
Article in English | MEDLINE | ID: mdl-1156267

ABSTRACT

Tests were carried out on pocket mice to ascertain their tolerance to elevated oxygen pressures alone and to a combination of hyperoxta and heat in excess of that expected during the flight of the mice on Apollo XVII. the mice withstood oxygen partial pressures up to 12 pst at normal room temperature (24 degrees C, 75 degrees F) over a period of 7 days. A few mice previously exposed to increased PO2 died in the course of exposure to an oxygen pressure of 10 pst or 12 psi (517 mm or 620 mm Hg) for 13 d in ambient heat of 32 degrees C (90 degrees F). Supplemental vitamin E and physiological saline loading given prior to exposure had no apparent protective effect. The overall conclusion was that the pocket mice which were to go on Apollo XVII could readily survive the ambient atmosphere to which they would be exposed.


Subject(s)
Adaptation, Physiological , Cosmic Radiation , Hot Temperature , Oxygen , Radiation Effects , Space Flight , Animals , Atmosphere Exposure Chambers , Atmospheric Pressure , Environment, Controlled , Mice , Partial Pressure , Sodium Chloride/administration & dosage , United States , Vitamin E/pharmacology
10.
Aviat Space Environ Med ; 46(4 Sec 2): 529-36, 1975 Apr.
Article in English | MEDLINE | ID: mdl-1156271

ABSTRACT

The final phase to fly five pocket mice in the Apollo XVII command module was carried out at the NASA Kennedy Space Center. Upon completion of the 13-d space flight, the package was removed from the spacecraft and, after having been purged with an oxygen-helium gas mixture, was flown to American Samo. Four of the five mice were recovered alive from the package. Analysis of the mouse that died during the flight revealed several factors that could have contributed to its death, the chief of which was massive hemorrhage in its middle ear cavities.


Subject(s)
Cosmic Radiation , Radiation Effects , Space Flight , Animals , Behavior, Animal , Brain/pathology , Ear Diseases/pathology , Ear, Middle/pathology , Female , Hemorrhage/pathology , Life Support Systems/instrumentation , Male , Mice , United States
11.
Aviat Space Environ Med ; 46(4 Sec 2): 582-606, 1975 Apr.
Article in English | MEDLINE | ID: mdl-1156275

ABSTRACT

In the five pocket mice flown on Apollo XVII, no evidence was found that the inner ear had been damaged, though poor fixation precluded detailed study. On the other hand, the middle ear cavity was involved in all the mice, hemorrhage having occurrred in response to excursions in pressure within the canister that housed the mice during their flight. The same occurred in flight control mice which had been subjected to pressure excursions of much the same magnitude. A greater degree of exudation into air cells and greater leukotaxis were noted in the flight animals than in the control animals. There was no increase in leukocyte population along the paths of the 23 cosmic ray particles registered in the subscalp dosimeters that traversed the middle ear cavities of the flight mice. The increased exudation and the greater response by leukocytes in the flight mice may have been causally related to the lesions found in their olfactory mucosa but there were no data in support of this possibility.


Subject(s)
Cosmic Radiation , Ear, Middle/radiation effects , Radiation Effects , Space Flight , Animals , Atmospheric Pressure , Cell Aggregation , Ear Diseases/pathology , Ear, Middle/anatomy & histology , Ear, Middle/pathology , Exudates and Transudates , Hemorrhage/pathology , Leukocytes , Mice , Oxides , Oxygen , Potassium , United States
12.
Aviat Space Environ Med ; 46(4 Sec 2): 561-81, 1975 Apr.
Article in English | MEDLINE | ID: mdl-1156274

ABSTRACT

The olfactory epithelium, but not the nasal respiratory epithelium, of the four pocket mice (Perognathus longimembris) that survived their flight on Apollo XVII showed both diffuse alterations and numerous disseminated focal lesions. The olfactory mucosa of the mouse that died during flight was also affected, but to a minor degree insofar as could be determined. All this was in contrast to the normal appearance of the olfactory mucosa of the numerous control animals. A number of possible causes were considered: systemic or regional infection; inhaled particulate material (seed dust); by-products from the KO2 bed in aerosol or particulate form; gas contaminants originating in the flight package; volatile substances from the dead mouse; weightlessness; and cosmic ray particle radiation. Where feasible, studies were conducted in an effort to rule in or rule out some of these potentially causative factors. No definitive conclusions were reached as to the cause of the lesions in the flight mice.


Subject(s)
Cosmic Radiation , Nasal Mucosa/radiation effects , Radiation Effects , Space Flight , Aerosols , Animals , Dust , Environmental Pollutants , Infections , Mice , Nasal Mucosa/anatomy & histology , Nasal Mucosa/pathology , Potassium , Radiation Monitoring , Seeds , United States
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