Biomedical subjects

L Jozsa

Publications and source records attributed to L Jozsa.

At least 19 recordsLinked to original sources

PubMed2006

Skeletal muscle HSP expression in response to immobilization and remobilization.

Heat shock proteins play an important regulatory role in the cellular defence. Oxidative stress is one of the factors inducing heat shock protein expression. This study tested the effects of 4 weeks of immobilization and subsequent remobilization on heat shock protein expression and oxidative stress in the lateral gastrocnemius and plantaris muscles of the rat. Active mobilization or free mobilization protocols were used for remobilization. In active mobilization, strenuous uphill treadmill running, twice a day, was started immediately after the immobilization and lasted for six days. Rats in the free mobilization group moved freely in their cages immediately after the immobilization. Expression of heat shock proteins was upregulated during the recovery from immobilization, especially in the lateral gastrocnemius muscle in the active mobilization group. However, markers of oxidative stress, such as protein carbonyls and 4-hydroxynonenal protein adducts, or activities of the antioxidant enzymes glutathione peroxidase and glutathione reductase, did not change after the immobilization and subsequent recovery. In summary, following immobilization, both intensive and spontaneous exercise upregulated the heat shock protein expressions in the lateral gastrocnemius muscle and partly in the plantaris muscle, which may contribute to the recovery from immobilization atrophy.

Animals↗

PubMed2000

Tenascin-C in the pathobiology and healing process of musculoskeletal tissue injury.

Tenascin-C (TN-C) is a hexabrachion-shaped extracellular matrix (ECM) protein which has very restricted expression in normal musculoskeletal tissues, but is expressed in large quantities in these tissues during embryogenesis as well as during regenerative and healing processes. TN-C is an elastic protein which has a number of binding sites for other extracellular matrix proteins as well as for cell membrane adhesion receptors. In addition, it can be stretched to several times its resting length, the ability of which is attributed to the stretch-induced unfolding of its fibronectin type III domains. In the musculoskeletal tissues, TN-C is present in the regions where high mechanical forces are transmitted from one tissue component to another, such as the myotendinous and osteotendinous junctions. Not surprisingly, it was recently presented that the expression of TN-C in the musculoskeletal tissues is regulated by the mechanical strain applied to their cells. Thus, taking into account the flexible structure of the TN-C and its site-specific expression pattern at sites exposed to heavy mechanical loads, TN-C is likely to play an important role in providing elasticity to the musculoskeletal tissues. This feature has a special significance in the degenerative and regenerative processes where the normal biomechanical environment of the musculoskeletal tissue is temporarily interrupted by injury. The rapidly increasing understanding of the structure and function of the ECM protein TN-C may well bring important insights into the clinical treatment of sports injuries in the future.

Animals↗

PubMed1999

Mechanical loading regulates tenascin-C expression in the osteotendinous junction.

Elastic extracellular matrix protein tenascin-C (TN) has very restricted expression in normal tissues, but is expressed in large quantities during embryogenesis and hyperplastic processes. To examine the importance of mechanical stress on the regulation of TN expression in vivo, the effects of various mechanical loading states (immobilization and three forms of subsequent remobilization) on the expression of TN were studied immunohistochemically at the bone-tendon attachment of the rat quadriceps muscle. This osteotendinous junction (OTJ) was selected as study site, since it receives its mechanical stimuli only from muscle contracting activity, which is easy to block by cast immobilization. TN was expressed abundantly in the normal OTJ. Following the removal of the mechanical stress from the junction by cast-immobilization of three weeks, the immunoreactivity of TN was almost completely absent. Normal mechanical stress in the form of free remobilization of eight weeks (free cage activity) resulted in a slight increase in TN expression, but could not restore the expression of TN to the level of the healthy contralateral leg. After the application of the increased mechanical stress (intensified remobilization of the eight weeks by low- or high-intensity treadmill running), the distribution and immunoreactivity of TN reached the level of the healthy contralateral limb in the low-intensity running group or even exceeded that in the high-intensity running group. High TN expression was seen around the chondrocytes and fibroblasts of the OTJ as well as around the collagen fibers of the tendon belly. We conclusively show that mechanical strain regulates the expression of TN in vivo, and propose that mechanical stress is a major regulator of TN expression in fibroblasts and chondrocytes. This may be an important aspect of the regulation of TN expression during embryogenesis, tendon degeneration, wound healing, bone formation, and in the other normal or regenerative morphogenetic processes TN is postulated to take part in.

Animals↗

PubMed1998

Location and distribution of non-collagenous matrix proteins in musculoskeletal tissues of rat.

The study assessed immunohistochemically the location and distribution of various non-collagenous matrix proteins (fibronectin, laminin, tenascin-C, osteocalcin, thrombospondin-1, vitronectin and undulin) in musculoskeletal tissues of rat. Fibronectin and thrombospondin-1 were found to be ubiquitous in the studied tissues. High immunoreactivity of these proteins was found in the extracellular matrix of the anatomical sites where firm bindings are needed, i.e. between muscle fibres and fibre bundles, between the collagen fibres of a tendon and at myotendinous junctions, osteotendinous junctions and articular cartilage. Tenascin-C was found in the extracellular matrix of regions where especially high forces are transmitted from one tissue component to the other, such as myotendinous junctions and osteotendinous junctions. Laminin was demonstrated in the basement membranes of the muscle cells and capillaries of the muscle-tendon units. Osteocalcin immunoreactivity concentrated in the extracellular matrix of areas of newly formed bone tissue, i.e. in the subperiosteal and subchondral regions, osteoid tissue and mineralized fibrocartilage zone of the osteotendinous junction. Mild vitronectin activity could be seen in the extracellular matrix of the osteotendinous and myotendinous junctions, and high activity around the bone marrow cells. Undulin could be demonstrated in the extracellular matrix (i.e. on the collagen fibres) of the tendon and epimysium only. However, it was co-distributed with fibronectin and tenascin-C. Together, these findings on the normal location and distribution of these non-collagenous proteins in the musculoskeletal tissues help to form the basis of knowledge against which the location and distribution of the these proteins in various pathological processes could be compared.

Animals↗

PubMed1998

Effects of immobilization and subsequent low- and high-intensity exercise on morphology of rat calf muscles.

After a cast immobilization of 3 weeks, the effects of 4-week remobilization by free cage activity or treadmill running on the morphology of the rat soleus and gastrocnemius muscles were studied. The studied morphometric parameters were: percentage volume of intramuscular connective tissue, capillary density, muscle fiber size, number of fibers with a pathological structural alteration, and fiber type distribution. In both muscles, immobilization of 3 weeks produced a significant increase in the connective tissue volume and number of fibers with pathological alterations, with a similar decrease in the capillary number and fiber size. At the same time, the relative amount of type I fibers decreased and type IIA fibers increased. Free remobilization and especially intensified remobilization by treadmill running significantly restored these values towards controls. These findings indicate that in rat soleus and gastrocnemius muscles immobilization-induced accumulation of intramuscular connective tissue, capillary loss, reduction in fiber size, accumulation of fibers with pathological structural alterations, and changes in fiber type distribution are to a great extent reversible phenomena, especially if remobilization is intensified by physical training. In clinical practice, this suggests that in patients with musculoskeletal injuries the postimmobilization rehabilitation should be early and effective.

Animals↗

PubMed1998

Free mobilization and low- to high-intensity exercise in immobilization-induced muscle atrophy.

After 3 wk of immobilization, the effects of free cage activity and low- and high-intensity treadmill running (8 wk) on the morphology and histochemistry of the soleus and gastrocnemius muscles in male Sprague-Dawley rats were investigated. In both muscles, immobilization produced a significant (P < 0.001) increase in the mean percent area of intramuscular connective tissue (soleus: 18.9% in immobilized left hindlimb vs. 3.6% in nonimmobilized right hindlimb) and in the relative number of muscle fibers with pathological alterations (soleus: 66% in immobilized hindlimb vs. 6% in control), with a simultaneous significant (P < 0.001) decrease in the intramuscular capillary density (soleus: mean capillary density in the immobilized hindlimb only 63% of that in the nonimmobilized hindlimb) and muscle fiber size (soleus type I fibers: mean fiber size in the immobilized hindlimb only 69% of that in the nonimmobilized hindlimb). Many of these changes could not be corrected by free remobilization, whereas low- and high-intensity treadmill running clearly restored the changes toward control levels, the effect being most complete in the high-intensity running group. Collectively, these findings indicate that immobilization-induced pathological structural and histochemical alterations in rat calf muscles are, to a great extent, reversible phenomena if remobilization is intensified by physical training. In this respect, high-intensity exercise seems more beneficial than low-intensity exercise.

Animals↗

PubMed1996

Number and morphology of mechanoreceptors in the myotendinous junction of paralysed human muscle.

The mechanoreceptor system of the myotendinous junction (MTJ) of human palmaris longus muscle obtained at autopsy was studied histologically from six patients with flaccid paralysis (complete acute tetraplegia 4-6 weeks before the autopsy, due to a spinal cord injury), eight patients with spastic paralysis (chronic hemiplegia due to cerebral stroke) and ten neurologically normal controls. Four types of nerve endings, Ruffini and Pacini corpuscles, Golgi tendon organs, and free nerve endings, could be identified in the MTJs of the controls. In the MTJs of the patients with flaccid and spastic paralysis, the free nerve endings were not present and the mechanoreceptors that were found were few in number, degenerated, fibrotic, and atrophic. These mechanoreceptors had lost their connection with the muscle fibres and tendon bundles and were frequently located within pathological accumulations of fatty tissue in the myotendinous region. The number and distribution of mechanoreceptors in the MTJ were almost identical in patients with flaccid and spastic paralysis.

Adult↗

PubMed1996

Expression of osteocalcin in the patella of experimentally immobilized and remobilized rats.

The exact mechanisms by which mechanical loading-unloading affects bone tissue are mostly unknown. Recently, osteocalcin, a direct product of osteoblasts, has been shown to reflect the activity of the mineralization phase of the newly formed bone matrix, and therefore, the in situ detection of osteocalcin could be used for studying the effects of physical activity-inactivity on the osteoblast function or bone formation in the target bone. In this study, the effect of various loading states (immobilization and three forms of subsequent remobilization) on the in situ expression of osteocalcin in the rat patellas and their osteotendinous junctions was studied immunohistochemically using a polyclonal rat antiosteocalcin as the primary antibody. Following immobilization for 3 weeks, the immunoreactivity of osteocalcin was markedly decreased or was completely absent in all the patellar areas which normally show intense reaction as a sign of mineralization of the newly formed bone, that is, in the subperiosteal and subchondral regions, in the osteoid tissue that lies on the surface of the trabecular bone, and around the cortical lacunae. The same was true in the mineralized fibrocartilage zone of the osteotendinous junction of the quadriceps tendon. Free remobilization for 8 weeks (free cage activity) could not improve the situation, but after intensified remobilization of the same duration (low and especially high intensity treadmill running) high osteocalcin expression was observed in the above-mentioned anatomic sites. These findings indicate that formation of new bone tissue is rapidly regulated by the loading states of the bone. Higher than normal activity seems to be needed to restore the bone formation from the disuseinduced depression to normal.

Animals↗

PubMed1996

Effects of immobilization, three forms of remobilization, and subsequent deconditioning on bone mineral content and density in rat femora.

Disuse is associated with bone loss, which may not be recoverable. It is not known whether intensified remobilization is beneficial in restoring disuse-related bone loss nor if any such benefit would depend upon continuing mobilization for its maintenance. After an immobilization period of 3 weeks, the effects of free remobilization (11 weeks), and low-and high-intensity treadmill running (11 weeks) with and without subsequent deconditioning (18 weeks) on the bone mineral content (BMC) and density (BMD) of the hindlimb femora of Sprague-Dawley rats (n = 98) were studied using a dual-energy X-ray absorptiometric (DXA) scanner. Our hypothesis was that intensified remobilization is beneficial in restoring the BMC and BMD from disuse to normal while subsequent deconditioning is deleterious to these parameters. Immobilization for 3 weeks produced a significant BMC and BMD loss in the immobilized left femur (range -4.4 to -12.8%; p < 0.05-0.001). In the groups with free remobilization (free cage activity), the body weight-adjusted BMCs and BMDs always remained below those in the controls (range -2.3 to -12.1%; p values ranging from NS to < 0.01). Both low- and high-intensity running restored BMC and BMD in the immobilized limb, the effect being better in the latter group. In both of these groups, the values of the immobilized left limbs and those of the free right limbs exclusively exceeded the corresponding values of the age-matched control rats (left limb values 3.0-21.1% higher with p values ranging from NS to < 0.01; right limb values 7.9-21.4% higher with p < 0.05-0.01). However, after the deconditioning period of 18 weeks, the above described beneficial effects of low- and high-intensity running were lost, the left and right limb BMC and BMD values being lower than those in the age-matched controls (range -3.8 to -8.7%; p values ranging from NS to < 0.05). In conclusion, this study clearly indicates the need for greater than normal activity to restore the BMC and BMD after disuse to normal levels. However, the benefits of intensified remobilization are lost if the activity is terminated, and therefore, after immobilization and disuse, bone loading activities should be continued, perhaps indefinitely.

Absorptiometry, Photon↗

PubMed1995

Effect of anterior cruciate ligament reconstruction with patellar tendon or prosthetic ligament on the morphology of the other ligaments of the knee joint. An experimental study in dogs.

The effect of anterior cruciate ligament replacement on the other ligaments of the knee, including the medial or lateral collateral and posterior cruciate ligaments, was studied histologically in the canine knee. The anterior cruciate ligament was replaced either with the medial third of the patellar tendon or with a prosthetic ligament. Histologic analysis was performed 3 months after prosthetic ligament implantation and 1 year after patellar ligament reconstruction. In all ligaments, numerous pathologic alterations were found. Degenerative changes such as glycosaminoglycan accumulation, metachromasia, collagenolysis, collagen necrosis, and lipomatosis were similar after 3 months and after 1 year. Granulation tissue, a sign that characterizes tissue repair, was seen only in those ligaments taken 3 months after anterior cruciate ligament surgery. Similar degenerative changes also were found in the ligaments of the knees with only a large medial arthrotomy (sham). In the contralateral control knees, the pathologic alterations were rare. Thus, open arthrotomy alone or with anterior cruciate ligament reconstruction seems to result in longstanding degenerative changes in all ligaments of the canine knee joint.

Animals↗

PubMed1994

Effects of free mobilization and low- to high-intensity treadmill running on the immobilization-induced bone loss in rats.

After an immobilization period of 3 weeks, the effects of free remobilization (8 weeks) as well as low- and high-intensity treadmill running on the bone mineral content (BMC) and density (BMD) of the hindlimbs of Sprague-Dawley rats (n = 70) were studied using a dual-energy x-ray absorptiometric scanner. In the low-intensity running program, the rats were allowed to move freely in the cage for 1 week, after which they started to run on a treadmill twice a day for 7 weeks. The speed of the treadmill was 20 cm/s, with an uphill inclination of 10 degrees. The running time was gradually increased from 20 minutes per session to 45 minutes per session. In the high-intensity group, the program was similar, with the exception that the speed of the treadmill was 30 cm/s, with an uphill inclination of 30 degrees. Immobilization for 3 weeks produced a significant BMC and BMD loss in the immobilized left femur and tibia (mean loss 9.6%, p < 0.001) but did not affect the right free limbs. Both low- and high-intensity running restored mineral content in the immobilized limb; however, an average 5% difference (p < 0.05) in mineral content of the right and left limb bones persisted. In the running groups, the values for the immobilized left limbs were at the same level or exceeded (range 3.8-11.6%, p < 0.05-0.01) and those of the free right limbs exclusively exceeded (range 5.3-15.9%, p < 0.05-0.01) the corresponding values of the age-matched control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

PubMed1993

Mechanoreceptors in human myotendinous junction.

The sensory-nerve-ending system of 40 myotendinous junctions of human palmaris longus and plantaris muscles was studied histologically. All the known four types of nerve endings were identified. The Ruffini corpuscles could be found in equally small numbers (one to five) in both the muscular and tendineal sites of the junction. Also the free nerve endings were distributed equally on both sites. The Pacini corpuscles were frequent in the tendineal site (six to 14), but rare in the muscular site (one to three). The Golgi tendon organs were, in turn, frequent in the muscular site (nine to 12) but rare in the tendineal site (one to four), respectively. Within the muscle and tendon parts of the junction, the distance between two mechanoreceptors was always more than 250 microns and the receptor distribution was homogeneous. Further studies are needed to give functional explanation for these anatomic findings.

Adult↗

PubMed1993

Atrophy and regeneration of rat calf muscles cause reversible changes in the number of nucleolar organizer regions. Evidence that also in nonproliferating cells the number of NORs is a marker of protein synthesis activity.

BACKGROUND: NORs are loops of DNA that transcribe to ribosomal RNA, and their number reflects the rDNA transcription, and, in this way, cell proliferation. EXPERIMENTAL DESIGN: The effect of muscle immobilization and remobilization on the number of nucleolar organizer regions (NORs) in the muscle cells and fibroblasts of rat calf muscles was studied histologically using a silver-staining technique (AgNOR). RESULTS: In muscle-cell nuclei, immobilization of 3 weeks produced a significant decrease in the number of AgNORs per nucleus. This phenomenon was reversible since, free remobilization of 4 weeks and especially intensified remobilization (free mobilization of 1 week plus treadmill running of 3 weeks) produced significant increase in the AgNOR counts. The treadmill running also produced a significant increase in the number of AgNORs in the muscle cells of contralateral (nonimmobilized) limbs. In intramuscular fibroblast nuclei, immobilization caused, in turn, a steady increase in the AgNOR count, the change being significant after 3 weeks. Free remobilization returned the count towards controls, and intensified remobilization returned it to the control level. CONCLUSIONS: Previous studies have shown that in the muscle cells immobilization decreases and remobilization (training) increases intracellular protein synthesis and that in the fibroblasts the opposite happens (immobilization increases and remobilization decreases intramuscular connective tissue formation). Our study gives indirect evidence that the number of NORs is a marker of ribosomal protein synthesis activity in non-proliferating cells. The cell-proliferation activity was proved to be zero using a proliferating-cell-nuclear-antigen technique.

Animals↗

PubMed1992

The effect of immobilization on myotendinous junction: an ultrastructural, histochemical and immunohistochemical study.

The effect of immobilization on the myotendinous junction of the calf muscles in the rat was studied histochemically, immunohistochemically and morphometrically with a transmission electron microscope. After 3 weeks of immobilization, the contact area between the muscle cells and tendineal collagen fibres was reduced by almost 50% in both type I (slow-twitch) and type II (fast-twitch) muscle fibres. The terminal finger-like processes of the muscle cells became shallow and cylindrical or were completely atrophied. Their basal membranes were slightly thickened. Histochemically, the most remarkable alteration in the myotendinous junction was the marked decrease in the sulphate containing glycosaminoglycans. In the basal lamina of the muscle fibres, the glycosaminoglycan and proteoglycan content was also reduced. Immunohistochemical analyses revealed that the amount of type III collagen was markedly increased on the myotendinous interface, but the amount and distribution of type I collagen was not affected by immobilization. These findings suggest that immobilization causes degenerative changes at the myotendinous junction, which, in turn, most likely decrease its tensile strength and may predispose it to rupture during activity.

Animals↗

PubMed1992

Ultrastructure and collagen composition of the myo-fascial junction in rat calf muscles.

The collagen composition and ultrastructural organization of the myo-fascial junction was studied using immunohistochemical techniques and electron microscopy. At the myo-fascial junction, a small amount of type-III collagen was found; however, the major collagen component was the type-I collagen. On the longitudinal sites of muscle cells, there were deep recesses and, within these, finger-like structures containing sarcomeres. In these recesses and in the finger-like structures of the myo-fascial junction, the sarcolemma was thickened (three times) in a similar way to the basal lamina at the myotendinous junction. Thin collagen fibers were closely associated with the thickened sarcolemma of the finger-like structures.

Animals↗

PubMed1991

Macromolecular composition of the myotendinous junction.

The macromolecular composition of the myotendinous junction of the rat Achilles tendon was investigated. Heparan sulphate, chondroitin sulphate, and/or dermatan sulphate could be detected in the terminal processes of the muscle cells, but neither heparin nor keratan sulphate was present. The presence of hyaluronic acid was also questionable. High concentrations of sulphate containing glycosaminoglycans could be demonstrated both in the sarcolemma membranes and extracellular region. The main collagenous component in the myotendinous junction was type I collagen. Also small amounts of type III collagen was found at the myotendinous interface. In addition, high concentrations of fibronectin was present on the muscle cell surfaces of the junction. These results showed that myotendinous junction is histochemically and immunohistochemically a highly specified area rich in various polysaccharides. The high concentration of the polysaccharides in the myotendinous interface may increase the adhesive force between the muscle cell membrane and tendineal collagen fibrils and, by this way, it may be important in improving the elastic buffer capacity of the junction against loading.

Animals↗

PubMed1991

Morphology and histochemistry of the myotendineal junction of the rat calf muscles. Histochemical, immunohistochemical and electron-microscopic study.

The macromolecular composition and morphometry of the myotendineal junction (MTJ) of slow-twitch (type 1) and fast-twitch (type 2) muscle fibers were studied in gastrocnemius-soleus-Achilles unit of the rat. Proteoglycans and glycosaminoglycans, type III collagen, fibronectin and laminin could be detected at the myotendineal junction. Due to the membrane folding finger-like processes were seen at the MTJ. The processes of type 1 fibers were greater in size. However, due to the subdivisions the processes of type 2 muscle fibers had a significantly greater surface length per muscle cell diameter than type 1 fibers. The myotendineal endings of both fiber types had a characteristic basal lamina, which was about three times thicker than in the longitudinal site of the same muscle cells. The basal lamina of type 1 fibers at the MTJ was significantly thicker than that of type 2 fibers.

Achilles Tendon↗

PubMed1991

Three-dimensional ultrastructure of human tendons.

The three-dimensional ultrastructure of human tendons has been studied. Epitenon and peritenon consist of a dense network of longitudinal, oblique and transversal collagen fibrils crossing the tendon fibres. The internal structure of tendon fibres is also complex. The collagen fibrils are oriented not only longitudinally but also transversely and horizontally. The longitudinal fibrils do not run only parallel but also cross each other forming spirals (plaits). These fibril bundles are bound together by a three-dimensional collagen fibril network of endotenon. In the myotendinous junction the surface of the muscle cells form processes. A network of tendineal collagen fibrils fills the recesses between the muscle cell processes penetrating the basement membrane of these processes. This complex ultrastructure of human tendons most likely offers a good buffer system against longitudinal, transversal, horizontal as well as rotational forces during movement and activity.

Adolescent↗