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Biomedical subjects

B J Martin

Publications and source records attributed to B J Martin.

At least 109 records · Page 6Linked to original sources

Regulation of myosin heavy-chain gene expression during skeletal-muscle hypertrophy.

Changes in the myosin phenotype of differentiated muscle are a prominent feature of the adaptation of the tissue to a variety of physiological stimuli. In the present study the molecular basis of changes in the proportion of myosin isoenzymes in rat skeletal muscle which occur during compensatory hypertrophy caused by the combined removal of synergist muscles and spontaneous running exercise was investigated. The relative amounts of sarcomeric myosin heavy (MHC)- and light (MLC)-chain mRNAs in the plantaris (fast) and soleus (slow) muscles from rats was assessed with cDNA probes specific for different MHC and MLC genes. Changes in the proportion of specific MHC mRNA levels were in the same direction as, and of similar magnitude to, changes in the proportion of myosin isoenzymes encoded for by the mRNAs. No significant changes in the proportion of MLC proteins or mRNA were detected. However, high levels of MLC3 mRNA were measured in both normal and hypertrophied soleus muscles which contained only trace amounts of MLC3 protein. Small amounts of embryonic and neonatal MHC mRNAs were induced in both muscles during hypertrophy. We conclude that the change in the pattern of myosin isoenzymes during skeletal-muscle adaptation to work overload is a consequence of changes in specific MHC mRNA levels.

Animals↗

Scanning electron microscopic study of hemodynamically induced tears in the internal elastic lamina of rabbit arteries.

A scanning electron microscopic investigation of tears in the internal elastic lamina of the afferent artery of experimental arteriovenous fistulae was undertaken to determine their site of initiation and to elucidate their nature. Carotid-jugular arteriovenous fistulae and contralateral common carotid arteriotomies were performed in rabbits sacrificed from two to 63 days post-operatively. Following de-endothelialization, scanning electron microscopy of the internal elastic lamina revealed predominantly transverse straight tears with sharp margins. Even in chronic fistulae the tears retained their sharp margins despite their propagation. No evidence of repair was observed. The tears commenced by rupture of the elastic trabeculae traversing the fenestrae. Enzymatic digestion of the internal elastic lamina did not resemble the hemodynamically induced tears and no evidence of elastolytic enzyme activity was detected. The tears suggest that the abnormally stressed elastic tissue has undergone some structural alteration leading to a reduction in its tensile strength.

Animals↗

Genomic structure and amino acid sequence domains of the human La autoantigen.

La is an autoimmune RNA-binding protein of 47 kDa that plays a role in the transcription of RNA polymerase III. Both genomic and complementary DNAs were isolated that encompass the coding sequence of the human La molecule. The genomic clones encompass 11 exons and a putative G/C-rich promoter upstream of the mRNA start site. The cDNA sequence encodes a protein of 408 amino acids and can be divided into two structural domains based upon amino acid content and protease sensitivity. An unusually long stretch of 130 amino acids, much of which was predicted to form a stable alpha-helix, was found near the middle of the protein between the two domains. A ribonucleoprotein (RNP) consensus sequence was found just NH2-terminal to the long alpha-helix. The RNP consensus sequence is split into two exons by the fifth intron. Expression of three separate fragments of the La protein in Escherichia coli showed that a strongly autoimmune-reactive portion resides in the fragment containing the RNP consensus sequence and most of the long alpha-helical core. Autoantibodies from La patients also reacted with the terminal regions of the protein, but the extent of reactivity varied among patients. Differences in reactivity of autoantibodies to each portion of La protein may reflect an evolution of recognition of different epitopes during the development of the autoimmune response. These findings support an antigen-driven mechanism for autoimmune reactivity.

Amino Acid Sequence↗

Classical genetic analysis of GABA-related seizures.

Differences in resistance to 3-mercaptopropionic acid (MP)-induced seizures exist between DBA/2Ibg and C57BL/6Ibg inbred strains of mice; C57BL/6Ibg mice are more resistant to MP-induced seizures. To determine the mode of inheritance for seizure resistance, a classical genetic analysis was conducted using these two parental strains, their F1, F2, and backcross generations. Latencies to seizure onset and tonus after intraperitoneal (IP) injections of MP (25-40 mg/kg) were quantified. For all populations mean latencies to onset and tonus decreased in a dose dependent manner with the hybrid generations exhibiting a seizure resistant phenotype resembling the C57BL/6Ibg strain. In general, female mice were less resistant to MP-induced seizures than males; however, a significant degree of resistance was retained by the C57BL/6Ibg females and their female progeny. A quantitative assessment of the pattern of inheritance for seizure resistance using a weighted least-squares regression approach indicated that an additive-dominance model explained latency to seizure onset data at 25, 35 and 40 mg/kg. However, at 30 mg/kg, the model required the addition of an epistatic parameter to best describe mean scores at this dose. The results of these analyses suggest that resistance to MP-induced seizures is transmitted in a dominant manner.

3-Mercaptopropionic Acid↗

Genetic differences in plasma corticosterone levels in response to nicotine injection.

Changes in plasma corticosterone (CCS) levels following intraperitoneal injections of nicotine were measured in four inbred mouse strains: DBA/2Ibg, C57BL/6Ibg, C3H/2Ibg, and A/J. In all four strains, nicotine produced a dose-dependent (0.5-2.0 mg/kg nicotine) increase in plasma CCS levels which peaked 10-30 min after injection. Saline increased plasma CCS levels in C57BL, A, and C3H, but not in DBA mice. After correcting for plasma CCS levels produced by saline injection, the nicotine-induced rise in plasma CCS was significantly lower for the C57BL strain than for the other three strains tested. These mouse strains also varied in their responses to saline injection with the rank order: C57BL greater than A = C3H greater than DBA. However, the two most divergent strains (C57BL and DBA) did not differ in the effects of a cold water stress. The response to nicotine was completely inhibited by mecamylamine in two strains tested (C3H and C57BL) whereas the response to saline injection was unaffected, suggesting that only the response to nicotine was mediated by nicotinic receptors. It is clear that elevations in plasma CCS induced either by saline injection or by nicotine are influenced by genetic factors.

Animals↗

Influence of genotype on nicotine-induced increases of plasma corticosterone in mice as a result of acute nicotine pretreatment.

Acute exposure to nicotine produces an elevation of plasma corticosterone levels in rodents. The consequences of repeated exposure to nicotine administered intraperitoneally (IP) were examined in three inbred strains of mice, DBA/2Ibg, C3H/2Ibg and A/J. These strains of mice have been shown previously to differ in a variety of behavioral and physiological responses to acute nicotine exposure. Mice were administered saline or 1.00 mg/kg nicotine IP, followed 30 min later by a range of nicotine doses (0.25-1.00 mg/kg). Strain differences were observed for the dose-response to the second injection; however, no effect of acute nicotine pretreatment was demonstrated. The observed lack of desensitization was consistent across genotype. An intragastric administration of a pretreatment dose of nicotine (4.00 mg/kg) also failed to produce desensitization to a subsequent IP nicotine injection in any strain. Increasing the time interval between injections to 45 min did not alter the CCS response. However, at 90 min between injections, a supersensitive CCS response was measured in all strains.

Animals↗

Supine position and sleep loss each reduce prolonged maximal voluntary ventilation.

Because of the prevalence of supine posture and sleep deprivation in both health and disease, we wondered how each of them influences prolonged maximal voluntary ventilation (MVV). Accordingly, we compared 12-second, 1-min, and 10-min isocapnic MVV supine with that measured in the upright posture in 8 healthy subjects. MVV decreased 6-10% supine, independent of test duration (p less than 0.01). Although end-expiratory lung volume was 0.47 liter lower during supine resting breathing (p less than 0.001), end-expiratory lung volumes during short-term MVV maneuvers were identical. To investigate any additional effect on MVV due to sleep loss, 12 healthy subjects performed 12-second, 1-min, and 30-min isocapnic MVV maneuvers in the supine position, either after normal sleep or after a 24-hour sleepless period. Sleep deprivation reduced MVV by 7-14%, again independent of test duration (p less than 0.05). Sleep loss also reduced the ventilation chosen to represent a submaximal (75%) breathing effect (p = 0.05), and it increased subjective ratings of fatigue and confusion (p less than 0.01). We conclude that supination and sleep deprivation together decrease both short- and long-term MVV by nearly 20%, with impairment of supination not caused by lung volume changes, and with the sleep loss effect occurring in tandem with a rise in the subjective assessment of breathing effort.

Adult↗

Hypomagnesaemia in elderly digitalised patients.

Hypomagnesaemia and hypokalaemia are known to predispose to digoxin toxicity. Elderly patients receiving diuretics may be at special risk. A 12-month survey of all patients receiving digoxin at the time of admission to our Geriatric Assessment Unit revealed 16% were hypomagnesaemic, whereas no patient was hypokalaemic. There is a need for greater awareness of the risk of magnesium depletion in elderly patients receiving concurrent diuretic and digoxin therapy.

Aged↗

Sleep loss and subsequent exercise performance.

The effect of sleeplessness on subsequent exercise performance is a difficult topic addressed by few workers, and is poorly understood. Sleep loss probably reduces VO2 max, although neither the causes nor the consequences for performance of this reduction have been determined. Sleep deprivation is not a physiological stress, and it may not change perceived exertion in exercise. Sleep loss severely hampers work requiring sizable cognitive input, providing evidence that sleep primarily serves the brain. The slow evolution of understanding of sleep-wake regulation hints that sleeplessness has other subtle central and peripheral effects, but the implications of these for exercise performance are unknown.

Animals↗

The identification of Eperythrozoon ovis in anemic sheep.

Eperythrozoon ovis, a rickettsial parasite of erythrocytes, was found in anemic lambs maintained for reproductive endocrinology research. The parasite was identified in the blood films of 13 animals in the flock of 30. The sexes were infected equally (7/16 males versus 6/14 females). The relationship between the severity of the anemia and the presence of organisms in blood was statistically significant. One animal died with severe anemia. Light, scanning electron, and transmission electron microscopy of peripheral erythrocytes revealed an extracellular organism identified as E. ovis. These findings indicate that this parasite can cause disease in sheep and therefore may interfere with biomedical research.

Anaplasmataceae Infections↗

Gastrointestinal transit during mild exercise.

Although exercise is often recommended as therapy for constipation, almost nothing is known of the effects of exercise on rates of movement of material in the gastrointestinal tract. In this study we investigated the influence of mild exercise on transit of a liquid meal from the mouth to the large intestine. Orocecal transit time was determined by a consistent elevation of H2 concentration in a rebreathing apparatus after ingestion of 30 g lactulose; the lactulose was part of a 360-kcal, 350-ml liquid meal. Comparison of transit time was made, in 12 young healthy subjects, between seated rest and a treadmill walk at 5.6 km/h up a 2% grade. The walk elevated heart rate from 64 +/- 4 to 109 +/- 5 beats/min, O2 uptake (VO2) from 0.29 +/- 0.02 to 1.20 +/- 0.07 l/min STPD, and final rectal temperature from 37.0 +/- 0.1 to 38.3 +/- 0.1 degrees C (all P less than 0.01). Exercise speeded transit of the liquid meal, with mean rises in H2 concentration taking place 66 +/- 10 min after ingestion at rest, compared with 44 +/- 6 min after food intake during exercise (P less than 0.02). H2 concentrations in the rebreathing apparatus showed similar base lines in the two experiments, and quantitative increases in H2 concentration, although shifted in time by exercise, were otherwise identical. Subjects with the slowest resting transit rates showed the largest exercise effects (r = 0.79, P less than 0.05). These results indicate that mouth-to-cecum transit of at least the first portion of a liquid meal-based nonabsorbable carbohydrate marker is significantly accelerated during mild exercise.

Adult↗

Diuretic-associated hypomagnesemia in the elderly.

Serum magnesium concentration was measured in 320 consecutive elderly patients (mean age, 81 years) receiving diuretic therapy at the time of hospital admission. When compared with serum concentrations of 250 elderly patients who were not taking diuretics at the time of hospital admission, only the group taking thiazide diuretics had a significantly reduced mean serum level. The 24-hour urine sampling from representative subgroups demonstrated impaired magnesium-conserving ability in hypomagnesemic subjects receiving loop and thiazide diuretic therapy. Patients taking therapy that included a potassium-sparing diuretic had no significant evidence of reduced magnesium-conserving ability. Dietary assessments of the study population revealed suboptimal magnesium intake in the diet.

Aged↗

Stress hormonal response to exercise after sleep loss.

While prolonged loss of sleep is unpleasant and demanding, it remains unclear if it blunts or enhances the physiological stress imposed by subsequent exercise. To investigate this, we deprived eight subjects of sleep prior to exercise to see if this altered the stress hormonal response to that exercise. In a first series of experiments, two fragmented nights of sleep preceded 30 min of heavy treadmill walking exercise. While sleep loss disturbed mood before and during exercise (p less than 0.05), it left stress hormonal levels (cortisol and beta-endorphin) in blood identical to control. In a second series, subjects performed light treadmill walking exercise for 3 h after 36 sleepless hours. As before, sleep deprivation disturbed mood before and throughout exercise (p less than 0.05), but failed to change blood levels of stress hormones. In both series, sleeplessness left heart rate, oxygen uptake, minute ventilation, and body core temperature unchanged in exercise. We conclude that sleep loss provokes psychological changes during subsequent exercise without measurably altering the stress hormonal response to that exercise.

Adult↗

Echocardiographic diagnoses in elderly patients with systolic murmurs and cardiac disease.

M-mode and 'real-time' echocardiography was employed to study 100 elderly with systolic murmurs and cardiac disease. Technically adequate recordings were obtained in 89 patients. Independent assessment of the echocardiographs showed good reproducibility. Aortic sclerosis was the most prevalent lesion, but did not by itself impair left ventricular function. The echocardiographic diagnosis of mitral regurgitation was significantly related to heart failure and atrial fibrillation. A link between murmur and cardiac disease was postulated in 40% of cases.

Aged↗

Pyrexia in infection in the elderly.

This prospective study investigated the common belief that pyrexia is frequently absent in elderly patients with infection. Oral temperature was closely monitored using both a mercury and an electronic thermometer in 150 ill elderly patients (mean age 81 years) of whom 80% were new admissions to this Unit. A scoring system was devised, based on investigation results and excluding temperature, to assess objectively the likelihood of infection. Seventy-one patients (47%) had 'definite' infection: 95% were pyrexial. A further eight of the nine patients with probable infection were pyrexial. There were no significant differences in mean temperature or other indices of infection between those who died of their infection and those who survived. Ten per cent of all pyrexias were detected only on the electronic thermometer, not on mercury measurement. In 12% of pyrexial patients, the pyrexia first appeared more than 12 h after temperature measurement started. With effective monitoring, pyrexia is detectable in the vast majority of infected elderly patients.

Age Factors↗

Ventilatory and treadmill endurance during acute semistarvation.

Little is known about respiratory muscle function in acute undernutrition, although an inadequate caloric intake is common in numerous disease states. Twelve young-adult, healthy female volunteers performed two familiarization experiments and were then studied after 7 days of consuming 40% of normal daily caloric intake as well as after 1 wk of normal caloric intake. In each experiment subjects performed tests of resting pulmonary function, inspiratory muscle strength, and ventilatory endurance, the last of which involved two 60-s and two 6-min isocapnic maximum voluntary ventilation maneuvers. Subjects then walked to exhaustion in 8-20 min on a treadmill. The caloric restriction did not affect performance of any breathing test but did lower endurance time in severe treadmill exercise (P less than 0.05). Basal metabolic rate was lowered, resting blood levels of free fatty acids and beta-hydroxybutyrate elevated, and glucose lowered following the caloric restriction (P less than 0.05). Blood lactate levels were lower during and after exercise following caloric restriction (P less than 0.05). We conclude that ventilatory muscle strength and endurance are fully preserved in caloric restriction severe enough to cause mild ketoacidosis and hypoglycemia, lowered basal metabolic rate, and decreased endurance in severe treadmill exercise.

Acute Disease↗