Lars Larsson

Muscle strength and fiber composition in athletes and sedentary men.

Members of Swedish national teams in track and field events (sprinting and jumping), downhill skiing, race walking, orienteering, and a group of sedentary men were studied to examine the relationship between muslce fiber characteristics in needle biopsy samples form m. vastus lateralis and muscle strength measured as peak torque during isokinectic knee extensions. In comparison with the sedentary group the following differences were found: a) percentage fast twitch fibers was lower in the endurance athetes, b) fast to slow twitch muscle fiber area ratio was higher in the track athletes, c)track athletes and downhill skier attained higher peak torque values at all angular velocities examined. The track athletes had, however, higher torque values at the fastest angular velocity as compared to the downhill skiers, whereas there was no differnce under isometric conditions. The proportion of fast twitch fibers was related to torque produced, especially at high motion velocity. The training also appeared to affect the force-velocity relationship.

Effects of age on enzyme-histochemical fibre spectra and contractile properties of fast- and slow-twitch skeletal muscles in the rat

Enzyme-histochemical fibre spectra and contractile properties were studied in fast-twitch (extensor digitorum longus (EDL) or tibialis anterior (TA)) and slow-twitch (soleus (S)) muscles of young adult (6 months) and old (20-24 months) male albino rats. It was found that ageing affected fibre size, fibre type proportions, and contractile properties of muscle tissue in both qualitative and quantitative terms and that these age-related alterations differed between fast- and slow-twitch muscles. In the fast-twitch TA and EDL, no differences were observed in either the total number of fibres, the cross-sectional area or the absolute and relative numbers of different muscle fibre types and subtypes between young adult and old animals. In the slow-twitch S, on the other hand, both the total number of muscle fibres and the average cross-sectional fibre area were smaller in the old animals. The fibre loss and fibre atrophy were most pronounced in type II fibres, especially type IIA. In TA, twitch force was higher and tetanus force was unaltered in the old as compared with the young adult animals, resulting in an increased twitch:tetanus ratio in old age. In S, on the other hand, both these forces were lower in the old animals and the twitch:tetanus ratio was accordingly unchanged with age. When the tetanus force was related to age-related differences in total muscle fibre cross-sectional area, no differences were found in the maximum force-generating capacity of maintained contractile material in either fast- or slow-twitch muscles between the two age groups. Probable mechanisms underlying the above alterations are discussed.

Muscle hypertrophy in bodybuilders

SummaryMuscle biopsy samples were obtained from m. vastus lateralis and m. deltoideus of three high caliber bodybuilders. Tissue specimens were analysed with respect to relative distribution of fast twitch (FT) and slow twitch (ST) fiber types and different indices of fiber area. In comparison to a reference group of competitive power/weight-lifters the following tendencies were observed: the percentage of FT fibers was less, mean fiber area was smaller and selective FT fiber hypertrophy was not evident. Values for fiber type composition and fiber size were more similar to values reported for physical education students and non-strength trained individuals. The results suggest that weight training induced muscle hypertrophy may be regulated by different mechanisms depending upon the volume and intensity of exercise.

Effects of ageing on enzyme-histochemical, morphometrical and contractile properties of the soleus muscle in the rat

Enzyme-histochemical, morphometrical and physiological properties were studied in the slow-twitch soleus muscle of male Wistar rats 2-25 months old. There was a clear age-related shift in the enzyme-histochemical profile of the muscle, resulting from transformation of fast-twitch muscle fibres to slow-twitch ones. This process occurred in younger animals up to the age of 7-8 months. At older ages there was a slight reduction in the total number of fibres and an increasing incidence of atrophic and angular fibres, indicating a denervation process. The tetanus force was reduced with age, but when it was related to the total muscle fibre cross-sectional area, no age-related difference was found. The contraction time was significantly altered only in 20-25-month-old animals, where it was prolonged, whereas the half-relaxation time showed a tendency towards prolongation throughout the entire age-span. Thus, the force-generating capacity of residual contractile material was not significantly affected by age and the age-associated decrease in the number of fast-twitch muscle fibres was not an important contributing factor to the decreased speed of contraction.

Quantitative and qualitative morphological properties of the soleus motor nerve and the L5 ventral root in young and old rats

Abstract The motor nerve to the soleus muscle and the L5 ventral root from young adult (3–6 months) and old (20–25 months) male Wistar rats were studied with regard to total number of myelinated nerve fibres, calibre spectra of myelinated fibres and morphological properties. The soleus muscle was examined with respect to total number of muscle fibres. A significant decrease in the number of myelinated nerve fibres was found in the old soleus nerves, and was mainly confined to the large-diameter fibres. Similarly, there was a significant decrease in the number of large myelinated fibres in the L5 ventral roots of old animals. Morphological changes in old nerves and spinal roots consisted of axonal degeneration with areas devoid of myelinated nerve fibres, and also myelin sheath irregularities, including myelin splitting with myelin balloon formation, infolded myelin loops and myelin reduplication. The axonal degeneration was more pronounced in the peripheral nerves than in spinal roots. In conformity with other studies, the soleus muscle showed an age-related decrease in the number of muscle fibres. These findings indicate that the decrease in fibre number in old soleus muscle is associated with degenerative neuronal changes and loss of α-motoneurons.

Aberrant post-translational modifications compromise human myosin motor function in old age.

Novel experimental methods, including a modified single fiber in vitro motility assay, X‐ray diffraction experiments, and mass spectrometry analyses, have been performed to unravel the molecular events underlying the aging‐related impairment in human skeletal muscle function at the motor protein level. The effects of old age on the function of specific myosin isoforms extracted from single human muscle fiber segments, demonstrated a significant slowing of motility speed (P < 0.001) in old age in both type I and IIa myosin heavy chain (MyHC) isoforms. The force‐generating capacity of the type I and IIa MyHC isoforms was, on the other hand, not affected by old age. Similar effects were also observed when the myosin molecules extracted from muscle fibers were exposed to oxidative stress. X‐ray diffraction experiments did not show any myofilament lattice spacing changes, but unraveled a more disordered filament organization in old age as shown by the greater widths of the 1, 0 equatorial reflections. Mass spectrometry (MS) analyses revealed eight age‐specific myosin post‐translational modifications (PTMs), in which two were located in the motor domain (carbonylation of Pro79 and Asn81) and six in the tail region (carbonylation of Asp900, Asp904, and Arg908; methylation of Glu1166; deamidation of Gln1164 and Asn1168). However, PTMs in the motor domain were only observed in the IIx MyHC isoform, suggesting PTMs in the rod region contributed to the observed disordering of myosin filaments and the slowing of motility speed. Hence, interventions that would specifically target these PTMs are warranted to reverse myosin dysfunction in old age.

Chest X-ray findings in relation to gender and symptoms: A study of patients with smear positive tuberculosis in Vietnam

The aim of the study was to analyse chest X-ray (CXR) findings among men and women with smear positive pulmonary tuberculosis (TB). All new cases of smear positive pulmonary TB diagnosed during 6 months in 23 districts in Vietnam were included in a cross-sectional study. 366 cases fulfilled the inclusion criteria. Pleuritis was demonstrated in 17% of the mens CXR versus 3% of the womens, p = 0.002. A miliary pattern was seen in 11% of the mens CXR versus 3% of the womens, p = 0.04. Hilar adenopathy was common and equally distributed among men and women (65% vs 61%). Dyspnoea was common among patients with pleuritis (67%) and a miliary pattern (65%). The radiological findings were more advanced in men than women, despite a similar time from symptom onset to diagnosis. The primary manifestations of TB found among men were unexpected in this setting with an HIV prevalence <0.1% at the time. The association with other risk factors for TB in men needs further investigation. The less advanced CXR findings in women may correspond to a slower rate of progression to smear positive disease, which would have implications for the possibilities of women to obtain a timely TB diagnosis.

Oxidative proteome alterations during skeletal muscle ageing

Sarcopenia corresponds to the degenerative loss of skeletal muscle mass, quality, and strength associated with ageing and leads to a progressive impairment of mobility and quality of life. However, the cellular and molecular mechanisms involved in this process are not completely understood. A hallmark of cellular and tissular ageing is the accumulation of oxidatively modified (carbonylated) proteins, leading to a decreased quality of the cellular proteome that could directly impact on normal cellular functions. Although increased oxidative stress has been reported during skeletal muscle ageing, the oxidized protein targets, also referred as to the ‘oxi-proteome’ or ‘carbonylome’, have not been characterized yet. To better understand the mechanisms by which these damaged proteins build up and potentially affect muscle function, proteins targeted by these modifications have been identified in human rectus abdominis muscle obtained from young and old healthy donors using a bi-dimensional gel electrophoresis-based proteomic approach coupled with immunodetection of carbonylated proteins. Among evidenced protein spots, 17 were found as increased carbonylated in biopsies from old donors comparing to young counterparts. These proteins are involved in key cellular functions such as cellular morphology and transport, muscle contraction and energy metabolism. Importantly, impairment of these pathways has been described in skeletal muscle during ageing. Functional decline of these proteins due to irreversible oxidation may therefore impact directly on the above-mentioned pathways, hence contributing to the generation of the sarcopenic phenotype.

Time course analysis of mechanical ventilation‐induced diaphragm contractile muscle dysfunction in the rat

Weaning from mechanical ventilation (MV) of long‐term intensive care unit (ICU) patients is delayed by impaired respiratory muscle function; however, the mechanisms that cause the impairment are not fully understood. A novel experimental rat ICU model was used for time‐resolved analyses (6 h to 2 weeks) of the effects of MV on diaphragm muscle fibre structure and function, and on gene and protein expression. A prompt and progressive decline of diaphragm muscle fibre function, preceding atrophy, occurred with MV, and at the end of 2 weeks residual diaphragm muscle fibre function was <15% of control levels. Cellular and subcellular analyses indicated that oxidative stress‐triggered protein modifications had significantly diminished diaphragm muscle fibre function. The novel finding that activation of proteolytic pathways and regulation of contractile protein synthesis were different in diaphragm and limb muscles has direct implications for the design of muscle‐specific intervention strategies.

BCG scar and tuberculin reactivity in children and adults

Bacille Calmette-Guérin (BCG) vaccination generally leads to scar formation and tuberculin skin test (TST) reactivity. This study aimed at analysing these 2 parameters and their correlation in a setting with a low prevalence of tuberculosis. Retrospectively, we analysed 314 children and 390 adults living in Sweden and known from records or individual recall to have undergone BCG vaccination. A BCG scar was present in 161 (51%) of the children and in 340 (87%) of the adults. Among children with a scar, 94 (58%) were TST-positive (≥6 mm) compared to 23 (15%) of 154 children lacking a visible scar. Among adults with a scar, 258 (76%) were TST- positive compared to 23 (46%) of 50 with no scar. Out of 152 non-vaccinated adults, 142 (94.4%) were TST-negative. When 175 TST-negative health care students were BCG-vaccinated in a prospective part of the study, 174 (99%) were found to develop a scar. In essence, the study showed a positive correlation between scar presence and TST reactivity. Furthermore, BCG vaccination of adults in the present setting resulted in consistent scar formation, while scar prevalence in previously vaccinated children was low.