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Biomedical subjects

H Kalimo

Publications and source records attributed to H Kalimo.

At least 37 records · Page 2Linked to original sources

Activation of myogenic precursor cells after muscle injury.

The time and site of satellite cell activation in contusive myofiber rupture with segmental necrosis were studied in rat by labeling the cells in S phase of mitotic cycle with bromodeoxyuridine. The labeled satellite cell nuclei did not appear before phagocytosis of the necrotized debris had started, usually 1 d after the trauma. Most labeled satellite cell nuclei were found in the necrotized part of the ruptured myofibers, whereas very few of them were detected in the surviving part. The proliferation of satellite cells was extensive during the first 4 d in the regeneration zone; thereafter, it declined and only few labeled nuclei were observed on day 7. These results suggest that necrosis alone is not sufficient as a signal for the satellite cell activation, but it is speculated that (growth?) factors released by the macrophages are needed. A great majority of myoblasts derive from local precursor cells, and satellite cells recruited from the surviving part do not significantly contribute to the regeneration. Most myonuclei needed in regenerating myofibers are produced early within the preserved basal lamina cylinders to be later distributed into those parts of myofibers, which extend into connective tissue between the stumps.

Animals

Inclusion body myositis and paramyxoviruses.

Inclusion body myositis (IBM) is a distinct type of muscle disease. The characteristic electron microscopic findings, intranuclear or intracytoplasmic inclusions composed of microtubular filaments, morphologically resemble paramyxovirus nucleocapsids. These findings and the reported immunoreactivity of the inclusions with mumps virus antibodies have suggested that inclusion body myositis is a chronic virus infection. We analyzed skeletal muscle specimens from three patients with characteristic light microscopic features and electron microscopically verified inclusions of IBM by immunocytochemistry using antibodies raised against members of the paramyxovirus group, and by in situ hybridization with a cRNA probe representing the mumps virus nucleocapsid gene. The specificity of the reactions was demonstrated with infected and uninfected cultured cells. No immunocytochemical staining or hybridization signal was observed in biopsy specimens from IBM patients. These findings speak against a paramyxovirus etiology of IBM.

Aged

Electromyography and morphology during regeneration of muscle injury in rats.

Healing of the partially ruptured rat gastrocnemius muscle was studied correlating electromyographical findings with morphological changes. Fibrillation potentials and positive sharp waves were seen both proximal and distal to the injury 7 days after the injury and disappeared in the proximal part by day 14 and in the distal part by day 21. Late components of motor action potential were observed from day 14 onwards. Denervation was mainly myogenic, i.e. caused either by rupture of myofibres, whence the abjunctional stump lost its contact with the neuromuscular junction on the adjunctional stump, or by necrosis of the segment of the ruptured myofibre lying underneath the neuromuscular junction. Lesser extent of denervation was neurogenic, i.e. caused by damage to intramuscular nerve fibres. The reinnervation occurs either by regeneration of the necrotized myofibres, by regeneration of the severed nerves, or by collateral innervation of new neuromuscular junctions in the abjunctional stumps. The present study indicates that electromyography may be useful in the diagnosis and follow-up of skeletal muscle injuries.

Animals

Localization of type I and III collagen and fibronectin production in injured gastrocnemius muscle.

The healing of muscle rupture consists of two simultaneous processes, regeneration of disrupted muscle fibers and production of connective tissue scar. These two processes are at the same time supportive to and competitive with each other. Their balanced progression is necessary for optimal healing. Synthesis of three connective tissue proteins, collagen types I and III and fibronectin, was analyzed during the regeneration process from 2 days to 3 weeks by Northern blot and in situ hybridization and immunohistochemistry. For this purpose a partial standard rupture of the gastrocnemius muscle was induced in 56 rats by a strike with a blunt spring-loaded hammer. Northern blot analysis of the specific mRNAs during the healing process revealed distinctly different expression patterns for fibronection and type I and III collagens. During the early stages (days 2 and 3) fibronectin, derived mainly from plasma, was abundant in the traumatized area, but local production of fibronectin mRNA by fibroblasts had also already started by day 2, closely followed by that of type III collagen. This early active synthesis of type III collagen and fibronectin was followed by a decrease after 1 week. The production of type I collagen mRNAs was activated somewhat later and remained elevated for at least 3 weeks. The muscle cells did not contain procollagen mRNAs. The observed sequence of connective tissue proteins reflects the particular function that each carries out during muscle wound healing (e.g., fibronectin in fibroblast trapping, type III collagen in plasticity/flexibility, and type I collagen in tensile strength).

Animals

Healing of skeletal muscle injury: an ultrastructural and immunohistochemical study.

The healing of gastrocnemius muscle injury induced with a spring-loaded hammer in rats was analysed ultrastructurally and immunohistochemically. The ends of the ruptured myofibers retracted, which resulted in a central blood filled cavity. Central zone (CZ) later becomes occupied by granulation tissue scar. CZ is surrounded by a zone where myofibers are necrotized and phagocytosed by days 2-3. Complete regeneration within the preserved basal lamina (BL) cylinders takes place in 5-7 days. The regeneration of myofibers across the scar follows a pattern different from that within BL cylinders. Thin, often branched, myotubes grow out of the BL cylinders into the granulation tissue, where they extend between fibroblasts and collagen fibrils, in general oriented parallel to the preserved myofibers. The extension of the regenerating myotube seems to take place primarily by local synthesis in the growth cone. Fusing myoblasts provide nuclei, mostly along the sides but also occasionally at the tip of myotubes. Some myoblasts seem to derive from undifferentiated cells in the granulation tissue. By three weeks only a few thin myotubes had extended across the gap between the stumps of the ruptured myofibers. Growing myotubes appear to attach to the surrounding connective tissue by specialized structures, an attachment which evidently transmits contraction force across the gap, allowing use of the injured limb before the healing is complete.

Animals

Lymphocyte migration into the skin: the role of lymphocyte homing receptor (CD44) and endothelial cell antigen (HECA-452).

Lymphocyte migration into the lymphoid organs and sites of inflammation is controlled by lymphocyte-endothelial cell interaction at sites where lymphocytes exit from the blood. Expression of Hermes-defined CD44 class of lymphocyte homing receptor and HECA-452 antigen specific for high-endothelium-mediating physiologic lymphocyte extravasation was studied in dermatitis herpetiformis, celiac disease, psoriasis, mycosis fungoides, lymphocytosis cutis, atopic dermatitis, and allergic contact dermatitis. Also, duodenal biopsies of patients suffering from dermatitis herpetiformis or celiac disease were studied for existence of these antigens. Infiltrating lymphocytes in the skin and in the duodenal area expressed homing receptor molecules when studied with monoclonal antibodies, Hermes-1 and Hermes-3, that recognize the CD44 class of molecules involved in lymphocyte binding to high endothelial venules in peripheral lymph nodes, mucosa-associated lymphatic tissues, and inflamed synovium. However, the HECA-452 antigen was not detected on the venules, neither in the skin nor in the duodenum. Even the venules possessing high endothelium morphologically were HECA-452 negative. These findings suggest the CD44 class of lymphocyte homing receptor(s) is also involved in lymphocyte homing to inflamed skin and the duodenal area of the gut. However, on the basis of HECA-452 staining, high endothelial venules in inflamed skin and duodenum are not antigenically identical with high endothelial venules in organized lymphoid tissues. This finding indirectly supports the idea that molecules and/or mechanisms mediating lymphocyte extravasation might be distinct in these organs.

Adult

Severe degeneration of rabbit vastus intermedius muscle immobilized in shortened position.

The authors have previously shown that passive daily mobilization of the rabbit hind limb immobilized with the knee in extension leads to necrosis of the deep thigh muscles and myositis ossificans-like periosteal bone formation. In this study the effect of immobilization alone on the rabbit hind limb muscles was examined similarly to that of immobilized limbs. Serum creatine kinase activities increased significantly and intravenously administered Evans blue albumin showed increased vascular permeability in the deep vastus intermedius muscle even on day 1. Necrotic fibers were clearly present in the deep part of the vastus intermedius muscle on day 5 in light and electron microscopy and in enzyme histochemistry. Fibrosis and atrophy were found later. The superficial portion of the vastus intermedius and the deep contralateral nonimmobilized vastus intermedius showed degenerative changes. Bone formation was not noted. The conclusion was that the deep vastus intermedius muscle composed almost exclusively of type I fibers is exceptionally prone to damage when immobilized in a shortened position. Contact of the necrotic muscle with the underlying periosteum is not alone sufficient to induce heterotopic ossification. The additional trauma caused by daily mobilization is needed for the myositis ossificans-like bone formation.

Animals

In situ detection of enterovirus genomes in mouse myocardial tissue by ribonucleic acid probes.

We have applied a sensitive in situ hybridization method for the detection of coxsackievirus RNA in myocardial tissue. Two radioactive cRNA probes were used: an RNA transcript representing the 5' end of poliovirus 3 which recognizes a highly conserved region among enteroviruses and an RNA transcript of a 1.1 kb fragment from the polymerase gene region of coxsackievirus B3. The reactivity of these probes was tested by dot-blot hybridization against a panel of enteroviruses. Formaldehyde-fixed and paraffin-embedded tissue of experimentally coxsackievirus B3 infected mice was analyzed for the localization of virus RNA. Both the probes gave signals in mouse myocardial cells, disseminated evenly in the heart tissue 7 days postinfection. At this time point, hybridization-positive cells and inflammatory reaction were mainly found in different areas that may be due to the inability of the immune system to recognize the infected cells before cytolysis. The samples were still positive when fixed 52 hours postmortem indicating that virus RNA is in a relatively stable form in the cells.

Animals

Expression of the myc proto-oncogenes in developing human fetal brain.

We have analysed c-myc, N-myc and L-myc gene expression in developing human fetal brain by Northern hybridization, RNAase protection and in situ hybridization. The unique zonal organization of the developing fetal brain allows a particularly good assessment of the coupling of myc gene expression to cell proliferation and differentiation in vivo. By Northern and in situ hybridization, L-myc as well as c-myc and N-myc transcripts in the brain were found in the post-mitotic cortical and intermediate layers, as well as in the mitotically active layers containing the neuroepithelial precursor cells. Consistent results were also obtained for L-myc using RNAase protection analysis. Both the 3.6 and 3.8kb forms of the L-myc mRNA, resulting from alternative splicing of intron I, were detected in layers of neuroectodermal origin, but not in the meninges or choroid plexus. We also extended L-myc expression and splicing analyses to other developing human fetal tissues. L-myc mRNA was expressed in several other fetal tissues, particularly in fetal skin. Predominantly intron I containing L-myc mRNA was observed in fetal striated and cardiac muscle. Thus, L-myc is expressed in a wider spectrum of developing tissues than previously known. Our findings also, show that L-myc as well as N-myc and c-myc expression is uncoupled from cell division in developing brain.

Blotting, Northern

Lymphocyte homing receptors and adhesion molecules in intravascular malignant lymphomatosis.

Intravascular malignant lymphomatosis (IML) is a highly malignant, recently recognized form of lymphoma. It is characterized by multifocal proliferation of malignant lymphocytes within small blood vessels, primarily in the central nervous system and skin, frequently resulting in circulatory disturbances. The cause of the impaired capability of the malignant lymphocytes to extravasate has remained unclear. We analyzed the presence of immunoreactivity for certain homing receptor and adhesion molecules associated with lymphocyte extravasation in 3 patients with this disease. Compared with non-neoplastic leukocytes, large malignant lymphocytes appeared either negative or only weakly positive for the leukocyte surface glycoprotein, CD18 that is the beta chain of the CDIIa/CD18 complex (lymphocyte-function associated antigen-I, LFA-I), which mediates cell-to-cell adhesion of lymphocytes. On the other hand, antibody to one of the proposed ligands for this complex, intercellular adhesion molecule-I, gave positive reactivity both on lymphocytes and on endothelial cells. Further, the malignant lymphoid cells stained positively with Hermes-3 antibody, which recognizes a common structure of CD44 class of molecules involved in lymphocyte homing. It was also shown that HECA-452 antigen, a marker of high endothelial venules (HEV) supporting lymphocyte extravasation, can be synthesized by an IML patient even at the site of inflammation but it is not prerequisite for extravasation of inflammatory lymphocytes. Our results suggest that the deficiency or absence of the adhesion molecule CDIIa/CD18 may contribute to the inability of the malignant lymphoid cells to extravasate in IML, and perhaps also to the high malignancy of this form of lymphoma.

Aged

Endogenous serum albumin content in brain after short-lasting epileptic seizures.

Epileptic seizures can transiently alter the blood-brain barrier. We have determined the content of extravasated endogenous serum albumin in the brain and its change with time after bicuculline (0.3 mg/kg) induced epileptic seizures of a few minutes' duration in conscious rats. The brains were perfused with saline in situ 5 min, 2 h, 24 h, 3 or 7 days after the injection of bicuculline. The content of endogenous serum albumin in the cerebral cortex, diencephalon, mesencephalon, pons and cerebellum was determined by rocket immunoelectrophoresis. At 5 min the extravasation was most marked in the diencephalon with levels above 99% of the confidence limit of control brains in 8 out of 9 brains. Higher levels were seen at 2 h than at 5 min in the cerebral cortex and the cerebellum. Since it is known that the barrier rapidly normalizes after seizures, these findings suggest redistribution probably along clearance pathways into the cerebrospinal fluid (CSF) and possibly re-entry of albumin into the parenchyma from the CSF. Four out of 6 rats still had increased albumin levels in the cerebral cortex at 24 h. At 72 h and 7 days no values differed from controls.

Animals

[Risk of central pontine myelinolysis in the treatment of severe hyponatremia].

Central pontine myelinolysis is a life-threatening condition involving the demyelination of axons in certain areas of the brain. It has been shown almost invariably to occur in connection with hospital care. In recent years, a connection has been noted between the rapid restitution of low serum sodium and the development of the condition. In this review, the most recent scientific information is summarized. It is concluded that the risk should always be considered in treating a hyponatremic patient. The serum sodium level should be raised slowly and the acute treatment ended before normal serum sodium levels are reached, ie when the patient is still slightly hyponatremic.

Demyelinating Diseases

Mitochondrial DNA polymorphism in Finnish families with Leber's hereditary optic neuroretinopathy.

Leukocyte mitochondrial DNA (mtDNA) from 17 Finnish families with Leber's hereditary optic neuroretinopathy and 70 maternally unrelated controls as well as skeletal muscle mtDNA from four of the Leber families and three controls was analyzed with 30 restriction enzymes. By this means, over 10% of the nucleotides of mtDNA were screened. No major deletion or insertion was found in any of the mtDNAs studied. The restriction fragment patterns of mtDNA showed no evidence of mtDNA heteroplasmy (mixture of different mtDNA types) in either blood or muscle cells. In all, 24 mtDNA types were observed in the material. In the maternal lines of Leber families, 11 mtDNA types were found, indicating no recent common maternal ancestor for the Finnish Leber families. In spite of several previously unknown polymorphisms, no mutation of mtDNA could be found exclusively in families with Leber's disease. However, a couple of mutations leading to amino acid replacements of mitochondrially encoded proteins were observed in certain Leber families only. These mutations have occurred in genes coding for subunits of NADH dehydrogenase, suggesting that a defect of the respiratory chain complex I may cause Leber's disease.

DNA, Mitochondrial

The N-myc proto-oncogene and IGF-II growth factor mRNAs are expressed by distinct cells in human fetal kidney and brain.

We studied the expression of the N-myc proto-oncogene and the insulin-like growth factor-II (IGF-II) gene in human fetuses of 16-19 gestational wk. Both genes have specific roles in the growth and differentiation of embryonic tissues, such as the kidney and neural tissue. Since continued expression of N-myc and IGF-II mRNAs is also a characteristic feature of Wilms' tumor, a childhood neoplasm of probable fetal kidney origin, we were particularly interested in the possibility that their expression might be linked or coordinately regulated in the developing kidney. Expression of N-myc mRNA was observed in the brain and in the kidney by Northern hybridization analysis. In in situ hybridization of the kidney, N-myc autoradiographic grains were primarily located over epithelially differentiating mesenchyme while most of the mesenchymal stromal cells showed only a background signal with the N-myc probe. N-myc mRNA was detectable throughout the developing brain with a slight accentuation in the intermediate zone cells in between the subependymal and cortical layers. Thus, even postmitotic neuroepithelial cells of the fetal cerebrum expressed N-myc mRNA. In Northern hybridization, IGF-II mRNA signal was abundant in the kidney but much weaker, though definite, in the brain. The regional distribution of IGF-II mRNA in the kidney was largely complementary to that of N-myc. IGF-II autoradiographic grains were located predominantly over the stromal and blastemal cells with a relative lack of hybridization over the epithelial structures. In the brain, IGF-II mRNA was about two- to threefold more abundant in the subependymal and intermediate layers than in the cortical plate and ependymal zone, respectively. The fetal expression patterns of the N-myc and IGF-II mRNAs are reflected by the types of tumors known to express the corresponding genes during postnatal life such as Wilms' tumor. However, the apparent coexpression of the IGF-II and N-myc genes in immature kidneys occurs largely in distinct cell types.

Autoradiography

Connective tissue changes of the multifidus muscle in patients with lumbar disc herniation. An immunohistologic study of collagen types I and III and fibronectin.

The connective tissue components, Types I and III collagen fibronectin, were immunohistologically analyzed using their specific antibodies for localization and semiquantitative estimation in 24 patients (11 women and 13 men, all under 55 years of age) operated on for herniated lumbar intervertebral disc. Nine cadavers without known back problems (2 women, 7 men) served as controls. In controls, Type I collagen was present in the endo- and perimysial structures of the muscle, more conspiciously in the former. Type III collagen, together with fibronectin, were more abundant in the perimysium than in the endomysium. Thickening of these structures was not evident in the controls. In most patients Types I and III collagen and fibronectin distribution was similar to that of the controls. However, fibrotic changes of both and endo- and perimysial structures involved all Types I and III collagen and fibronectin in ten cases. In two patients an increase in Type I collagen staining intensity in the endomysium was recorded and thickening of the endomysial structures was observed in six patients. There were correlations with the severity of the connective tissue structural changes to atrophy of the muscle and furthermore to disability of the patient in the 1-year postoperative check-up. These findings suggest that if marked fibrosis of the muscle occurs, it can be a factor impairing recovery from the disease during the long-term postoperative course.

Adult

Two cases of Dandy-Walker syndrome and chronic polyneuropathy.

The paper describes a so far unreported combination of Dandy-Walker syndrome and chronic hereditary polyneuropathy in 2 boys. One of the boys has a de- and remyelinating motor and sensory polyneuropathy, with either an autosomal recessive mode of inheritence or a sporadic occurrence. The other has an autosomal dominant form of mild polyneuropathy with tomaculum formations in myelinated fibers, corresponding to hereditary neuropathy with liability to pressure palsies.

Adult

Lumbar muscles: structure and function.

We review new data derived from careful dissection studies on the macroscopic anatomy, innervation and function of the lumbar muscles, as well as information on the fibres in these muscles. The new findings correct previous misconceptions of the functional anatomy of the lumbar muscles. The innervation and function of the erector spinae and multifidus muscles are so different that they cannot be classified as a single unit. The new interpretation of the innervation of multifidus muscle is of importance, for example, for the neurophysiological examination of the lumbar muscles. The relative number of the slow and fast type of muscle fibres in lumbar muscles varies considerably, and selective atrophy of the fast fibres seems to ensue from inactivity, not only in patients with back pain but also in sedentary controls. The atrophy may be corrected by adequate exercise. Both the fibre type composition and degree of atrophy may well influence a person's susceptibility to low back pain arising from the muscles.

Adult