Sigurd Lindal - Academia.edu (original) (raw)
Papers by Sigurd Lindal
Neuromuscular Disorders, 2012
We report four cases of focal myositis. The patients, three men and one woman, had painful muscle... more We report four cases of focal myositis. The patients, three men and one woman, had painful muscle hypertrophy, affecting four different sites. MRI confirmed the muscle enlargement and oedema. Electromyography revealed evidence of acute and chronic denervation in all four cases. Muscle biopsy was available in three and confirmed features suggestive of focal myositis. Based on our patient material, we suggest that chronic nerve irritation, such as compression, can lead to muscle hypertrophy which, when prolonged, provokes fibre necrosis and secondary inflammation. Our finding in four patients having hypertrophy involving four different sites, leads us further to suggest that this may be the common mechanism behind focal myositis.
The European Journal of Surgery
Cystic lymphangioma of the small-bowel mesen-fever and chills and present clinical and pathologic... more Cystic lymphangioma of the small-bowel mesen-fever and chills and present clinical and pathologic tery is a rare manifestation of an intraabdominal features. Furthermore, etiology and differential tumor in elderly patients. We present a case of a diagnosis of this tumor are discussed. (Pathology small-bowel mesentery lymphangioma,
Ultrastructural Pathology
Methotrexate (MTX) is a clinically important cytostatic antifolate. The study describes the acute... more Methotrexate (MTX) is a clinically important cytostatic antifolate. The study describes the acute effects of maximum tolerated doses of MTX or its major metabolite 7-hydroxymethotrexate (7-OH-MTX) on the ultrastructure of rat liver and kidneys. The ultrastructural changes in rats receiving MTX or 7-OH-MTX were, in principle, indistinguishable and their severity and extension increased with time of survival or doses of medication. All lesions were focal, microvascular, or parenchymal. Microvascular changes were more severe in nature when blood cells were present. The endothelial cells were swollen with loss of pinocytotic vesicles, their luminal plasma membrane formed blebs or were disrupted. Partly detached endothelial cells or deendothelialized areas, various types of white blood cells, in particular, neutrophil granulocytes, were observed in the microcirculation. Single platelets or small platelet aggregates were found either in the lumen or adhering to deendothelialized areas of injured endothelial cells. Hepatocytes exhibited steatosis, edema, and manifest single cell necrosis. There were also nuclear changes, marked proliferation of smooth endoplasmatic reticulum, increased amounts of intracellular lipid vacuoles, and a decrease in glycogen particles in hepatocytes. The kidney presented the major changes in the tubules and in the interstitial part. MTX and 7-OH-MTX acute toxicity may primarily be related to microvascular perturbation.
Acta Neurologica Scandinavica
ABSTRACT
The American journal of physiology
We previously showed that endothelin-1 (ET-1) causes accumulation of leukocytes in the pulmonary ... more We previously showed that endothelin-1 (ET-1) causes accumulation of leukocytes in the pulmonary microvasculature and increases vascular permeability in isolated rat lungs provided the presence of leukocytes in the perfusate. In the present study, we examined the time sequence for morphological changes induced by ET-1 in rat alveolar tissue. For this purpose we used morphometric analysis based on lung transmission electron micrographs. Morphometry was performed by point counting, and data were expressed as relative volume density. ET-1 (0.06, 0.6, and 6 nmol/kg) was infused into the internal jugular vein, and the animals were killed at certain points of time. The lungs were fixed by endotracheal instillation of McDowell's fixative. Infusion of ET-1 (0.06 or 0.6 nmol/kg) caused no significant morphological changes in the rat alveolar tissue as assessed by morphometric examination. A sevenfold increase in volume density of platelets was seen 5 min after infusion of ET-1 6 nmol/kg....
Micron and Microscopica Acta, 1990
B. melaninogenicus, B. veroralis, W. recta, B. buccae and B. heparinolyticus were among the most ... more B. melaninogenicus, B. veroralis, W. recta, B. buccae and B. heparinolyticus were among the most hydrophilic in this study. The presence of a crystalline surface layer (S-layer) was verified in the strains of the latter three species as well as in E. yurii, which was clearly the most hydrophobic species. The results suggest that the S-layers of oral anaerobic bacteria may be important determinants of cell surface hydrophobicity. The ultrastructure of the capsular layer of both hydrophilic and hydrophobic strains of seven Bacteroides spp., two Porphyromonas spp., E. yurii and W. recta was studied by electron microscopy. While no capsular material was present outside the S-layer of W. recta and E. yurii strains, most other strains had an intensively stained, dense layer of extracellular polymeric substance of varying thicknesses (10-30 nm). In addition, a much thicker sparse capsular layer was observed in some strains. With the exception of B. intermedius and the S-layer species the strains with a thick capsule were more hydrophilic than the strains with little or no extracellular polymeric material. However, also those S-layer strains of B. buccae and W. recta that were lacking a capsule were equally or more hydrophilic than the PMNLs. Fimbriae of P. gingivalis did not seem to be important determinants of cell surface hydrophobicity.
Clinical Neurophysiology, 2014
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 20, 1991
Mitochondrial myopathy can be caused by several metabolic defects in the mitochondria. Cells with... more Mitochondrial myopathy can be caused by several metabolic defects in the mitochondria. Cells with high levels of oxidative metabolism, such as skeletal muscle, myocardium and brain cells, are particularly vulnerable to these defects. We describe the structural changes in muscle biopsies from 49 patients with mitochondrial myopathy. The younger patients were often symptom-free, but the possibility of a genetic defect was suggested by the family history. "Ragged-red fibres" were found in 10% of the biopsies. Typical paracrystalline inclusions were seen in the mitochondria of the oldest patients. Electron-lucent matrix and increased thickness of the inner membranes of the mitochondria in particular were found in the younger patients. Disorganization of cristae, with cristolysis and unfolding of the cristae was also found. We suggest that structural mitochondrial changes in mitochondrial myopathy constitute a stepwise process and that the mitochondrial alterations of the crist...
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 10, 2001
Skin biopsy for quantification of intraepidermal nerve fibre density has recently been introduced... more Skin biopsy for quantification of intraepidermal nerve fibre density has recently been introduced as a method for diagnosis of peripheral neuropathies. Immunostaining by antibody to protein gene product 9.5 has proved particularly useful because it selectively visualizes the epidermal nerve fibres. We describe the procedure on the basis of relevant literature and our own experience. Results from investigations of 56 healthy individuals and three patients with small fibre involvement as part of their neuropathy are presented. In the healthy individuals, the mean density of epidermal fibres was 12.4 (SD 4.6), median 11.3 and range 6.0-26.1. Three patients with small fibre neuropathy had low intraepidermal nerve fibre density. Skin biopsy for determination of intraepidermal nerve fibre density is a simple and non-painful procedure. Skin biopsies can be done repeatedly and may be used for the purpose of monitoring potential therapeutic agents.
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 20, 2001
Transmission electron microscopy (TEM) is an important diagnostic tool in surgical pathology. We ... more Transmission electron microscopy (TEM) is an important diagnostic tool in surgical pathology. We give an overview, based on our own experience, of the application of TEM in diagnostic pathology. In spite of its potential for high-grade resolution, the actual use of TEM in diagnostic pathology is rather limited. TEM is mandatory in the examination of kidney and muscle biopsies and is often indicated when a metabolic disease is suspected. However, in many centres its importance in tumour pathology has declined because of the advances in the field of immunohistochemistry. TEM requires a great deal of resources and high levels of skills in tissue processing and diagnostic interpretation. The TEM diagnosis must be integrated with light microscopical and, often, immunohistopathological findings, as well as with the clinical data. We therefore recommend close collaboration between the clinician and the laboratory with regard to biopsy indication, handling of samples, and the final diagnosis.
Human reproduction (Oxford, England), 1993
Mitochondrial dysfunction reduces aerobic energy production and results in symptoms from various ... more Mitochondrial dysfunction reduces aerobic energy production and results in symptoms from various tissues, depending on metabolic demands. Mitochondrial adenosine triphosphate (ATP) is essential for sperm motility. Sperm motility was investigated in a patient with a mitochondrial disease caused by reduced activity of the mitochondrial enzyme complexes I and IV, and in two control subjects. Spermatozoa were cultured in media containing various energy substrates. Motility was judged by light microscopy, and ultrastructure by transmission electron microscopy. In the patient with mitochondrial disease, 12% of the spermatozoa were motile in the medium containing only glucose. There was a three-fold increase in motile spermatozoa when pyruvate and succinate were present together with glucose. In contrast, the spermatozoa of both control subjects had best motility in the presence of substrates for complex I, and no further increase was observed when succinate was added. Glucose and pyruvate...
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 20, 1994
In this review we describe surgical methods for open muscle biopsy. In order to obtain optimal ti... more In this review we describe surgical methods for open muscle biopsy. In order to obtain optimal tissue quality, correct handling of the muscle specimens at all stages of the procedure is essential. A technologist who is familiar with the procedure should be present in the operating room. This is important to ensure that specimens for histochemical or biochemical studies are frozen immediately and specimens for electron microscopy are fixed without delay. We describe procedures for processing the specimens for cryostat sections, paraffin sections and electron microscopy, and a simple method for handling muscle specimens in local hospitals before transfer to a hospital with a neuropathological service.
Progress in clinical and biological research, 1989
1. Prog Clin Biol Res. 1989;306:129-33. Maternal inheritance in a family with mitochondrial encep... more 1. Prog Clin Biol Res. 1989;306:129-33. Maternal inheritance in a family with mitochondrial encephalomyopathy. Torbergsen T, Borud O, Mathiesen E, Lindal S, Gustavson KH. Department of Neurology, University Hospital, Tromsø University, Norway. ...
PLoS ONE, 2011
Limb-Girdle Muscular Dystrophy type 2I (LGMD2I) is an inheritable autosomal, recessive disorder c... more Limb-Girdle Muscular Dystrophy type 2I (LGMD2I) is an inheritable autosomal, recessive disorder caused by mutations in the FuKutin-Related Protein (FKRP) gene (FKRP) located on chromosome 19 (19q13.3). Mutations in FKRP are also associated with Congenital Muscular Dystrophy (MDC1C), Walker-Warburg Syndrome (WWS) and Muscle Eye Brain disease (MEB). These four disorders share in common an incomplete/aberrant O-glycosylation of the membrane/extracellular matrix (ECM) protein a-dystroglycan. However, further knowledge on the FKRP structure and biological function is lacking, and its intracellular location is controversial. Based on immunogold electron microscopy of human skeletal muscle sections we demonstrate that FKRP co-localises with the middle-to-trans-Golgi marker MG160, between the myofibrils in human rectus femoris muscle fibres. Chemical cross-linking experiments followed by pairwise yeast 2-hybrid experiments, and co-immune precipitation, demonstrate that FKRP can exist as homodimers as well as in large multimeric protein complexes when expressed in cell culture. The FKRP homodimer is kept together by a disulfide bridge provided by the most N-terminal cysteine, Cys6. FKRP contains N-glycan of high mannose and/or hybrid type; however, FKRP N-glycosylation is not required for FKRP homodimer or multimer formation. We propose a model for FKRP which is consistent with that of a Golgi resident type II transmembrane protein. Citation: Alhamidi M, Kjeldsen Buvang E, Fagerheim T, Brox V, Lindal S, et al. (2011) Fukutin-Related Protein Resides in the Golgi Cisternae of Skeletal Muscle Fibres and Forms Disulfide-Linked Homodimers via an N-Terminal Interaction. PLoS ONE 6(8): e22968.
Neuromuscular Disorders, 2014
Cardiovascular Toxicology, 2010
To examine the response to chronic high-dose angiotensin II (Ang II) and a proposed milder respon... more To examine the response to chronic high-dose angiotensin II (Ang II) and a proposed milder response in female hearts with respect to gene expression and ischemic injury. Female and male litter-matched rats were treated with 400 ng kg -1 min -1 Ang II for 14 days. Hearts were isolated, subjected to 30-min ischemia and 30-min reperfusion in combination with functional monitoring and thereafter harvested for gene expression, WB and histology. Ang II-treated hearts showed signs of non-hypertrophic remodeling and had significantly higher end diastolic pressure after reperfusion, but no significant gender difference was detected. Ang II increased expression of genes related to heart function (ANF, b-MCH, Ankrd-1, PKC-a, PKC-d TNF-a); fibrosis (Col I-a1, Col III-a1, Fn-1, Timp1) and apoptosis (P53, Casp-3) without changing heart weight but with 68% increase in collagen content. High (sub-toxic) dose of Ang II resulted in marked heart remodeling and diastolic dysfunction after ischemia without significant myocyte hypertrophy or ventricular chamber dilatation. Although there were some gender-dependent differences in gene expression, female gender did not protect against the overall response.
Upsala Journal of Medical Sciences, 2009
Muscle biopsy is an important diagnostic tool in the investigation of children with neuromuscular... more Muscle biopsy is an important diagnostic tool in the investigation of children with neuromuscular disorders. This report presents the experience with paediatric muscle biopsies during a 5-year period at a routine pathology laboratory. A total number of 58 cases were included, and indications, microscopical findings, and final histopathological diagnoses were recorded. A total of 21 biopsies were from females (36%) and 37 biopsies from males (64%); 53% of the cases were from children under 2 years of age. Major pathological findings were found in 30% comprising muscular dystrophy, neurogenic atrophy, and congenital and metabolic disorders, even in cases with vague clinical manifestations. These findings confirm the high diagnostic yield of muscle biopsies, especially as new techniques have been introduced such as immunohistochemistry. Muscle pathology is difficult and emphasizes the importance of this service being undertaken by specialized laboratories with an experienced staff. Microscopical examination of muscle biopsies should be based on adequate clinical information, demonstrating the necessity of close contact between pathologists and referring physicians.
Ultrastructural Pathology, 1992
From 1986 to 1991, 472 muscle biopsy specimens from patients from different hospitals in Norway w... more From 1986 to 1991, 472 muscle biopsy specimens from patients from different hospitals in Norway were examined. Of these, 364 were embedded for electron microscopy, and 194 were examined with electron microscopy. Ultrastructural alterations in the mitochondria were detected in 49 of these specimens. Characteristic electron microscopic findings included subsarcolemmal accumulation of abnormal mitochondria of various shapes and sizes, often containing electron-dense granules and sometimes lipid vacuoles in the mitochondria and diffusely electron-lucent matrix space. Paracrystalline inclusion bodies were seldom seen in specimens from young patients, but in some cases mitochondrial electron-dense granules at the cristae were found. These amorphous densities are consistent with lipoproteins, suggesting that they may represent an early stage of paracrystalline inclusions. Biochemical and genetic exploration of the patients with biopsy specimens suggesting mitochondrial disease indicated maternally genetic inheritance and an enzyme defect in the respiratory chain in 21 patients in two families. Three patients had MELAS syndrome, 7 Marinesco-Sjögren syndrome, and 2 Kearns-Sayre syndrome. Five family members had ptosis, cardiomyopathy, mild myopathy, and increased lactate in cerebrospinal fluid and serum. In addition to the diseases mentioned above, changes in the mitochondria were detected in other conditions such as Rett's syndrome (n = 1), ornithine transcarbamylase deficiency (n = 2), and hypothyroidism (n = 2) as well as in 3 patients with clinical and laboratory results indicative of inflammatory myopathy and 3 patients with clinical and laboratory findings consistent with peripheral neuropathy. It is concluded that, although ultrastructural changes in the mitochondria may represent unspecific findings, electron microscopic examination of muscle biopsy specimens is a useful screening method to select specimens for further biochemical analysis and to obtain an early and more precise diagnosis of the disease.
Ultrastructural Pathology, 2010
In this study cerebral ultrastructure was examined in an in vivo rat model, after rewarming from ... more In this study cerebral ultrastructure was examined in an in vivo rat model, after rewarming from profound hypothermia (15-13 degrees C). Animals held at 37 degrees C served as controls. After rewarming, brains were examined by electron microscope. Micrographs were taken randomly, analyzed anonymously, and quantified by morphometry. Serum analysis of the stress marker S-100beta was carried out in identical groups. The most striking findings in rewarmed animals, when compared to controls, were alterations of myelin sheaths (p<.008) and elevated S-100beta (p<.0001). This indicates that cells in the central nervous system are susceptible to injury in an experimental model of accidental hypothermia and rewarming.
Neuromuscular Disorders, 2012
We report four cases of focal myositis. The patients, three men and one woman, had painful muscle... more We report four cases of focal myositis. The patients, three men and one woman, had painful muscle hypertrophy, affecting four different sites. MRI confirmed the muscle enlargement and oedema. Electromyography revealed evidence of acute and chronic denervation in all four cases. Muscle biopsy was available in three and confirmed features suggestive of focal myositis. Based on our patient material, we suggest that chronic nerve irritation, such as compression, can lead to muscle hypertrophy which, when prolonged, provokes fibre necrosis and secondary inflammation. Our finding in four patients having hypertrophy involving four different sites, leads us further to suggest that this may be the common mechanism behind focal myositis.
The European Journal of Surgery
Cystic lymphangioma of the small-bowel mesen-fever and chills and present clinical and pathologic... more Cystic lymphangioma of the small-bowel mesen-fever and chills and present clinical and pathologic tery is a rare manifestation of an intraabdominal features. Furthermore, etiology and differential tumor in elderly patients. We present a case of a diagnosis of this tumor are discussed. (Pathology small-bowel mesentery lymphangioma,
Ultrastructural Pathology
Methotrexate (MTX) is a clinically important cytostatic antifolate. The study describes the acute... more Methotrexate (MTX) is a clinically important cytostatic antifolate. The study describes the acute effects of maximum tolerated doses of MTX or its major metabolite 7-hydroxymethotrexate (7-OH-MTX) on the ultrastructure of rat liver and kidneys. The ultrastructural changes in rats receiving MTX or 7-OH-MTX were, in principle, indistinguishable and their severity and extension increased with time of survival or doses of medication. All lesions were focal, microvascular, or parenchymal. Microvascular changes were more severe in nature when blood cells were present. The endothelial cells were swollen with loss of pinocytotic vesicles, their luminal plasma membrane formed blebs or were disrupted. Partly detached endothelial cells or deendothelialized areas, various types of white blood cells, in particular, neutrophil granulocytes, were observed in the microcirculation. Single platelets or small platelet aggregates were found either in the lumen or adhering to deendothelialized areas of injured endothelial cells. Hepatocytes exhibited steatosis, edema, and manifest single cell necrosis. There were also nuclear changes, marked proliferation of smooth endoplasmatic reticulum, increased amounts of intracellular lipid vacuoles, and a decrease in glycogen particles in hepatocytes. The kidney presented the major changes in the tubules and in the interstitial part. MTX and 7-OH-MTX acute toxicity may primarily be related to microvascular perturbation.
Acta Neurologica Scandinavica
ABSTRACT
The American journal of physiology
We previously showed that endothelin-1 (ET-1) causes accumulation of leukocytes in the pulmonary ... more We previously showed that endothelin-1 (ET-1) causes accumulation of leukocytes in the pulmonary microvasculature and increases vascular permeability in isolated rat lungs provided the presence of leukocytes in the perfusate. In the present study, we examined the time sequence for morphological changes induced by ET-1 in rat alveolar tissue. For this purpose we used morphometric analysis based on lung transmission electron micrographs. Morphometry was performed by point counting, and data were expressed as relative volume density. ET-1 (0.06, 0.6, and 6 nmol/kg) was infused into the internal jugular vein, and the animals were killed at certain points of time. The lungs were fixed by endotracheal instillation of McDowell's fixative. Infusion of ET-1 (0.06 or 0.6 nmol/kg) caused no significant morphological changes in the rat alveolar tissue as assessed by morphometric examination. A sevenfold increase in volume density of platelets was seen 5 min after infusion of ET-1 6 nmol/kg....
Micron and Microscopica Acta, 1990
B. melaninogenicus, B. veroralis, W. recta, B. buccae and B. heparinolyticus were among the most ... more B. melaninogenicus, B. veroralis, W. recta, B. buccae and B. heparinolyticus were among the most hydrophilic in this study. The presence of a crystalline surface layer (S-layer) was verified in the strains of the latter three species as well as in E. yurii, which was clearly the most hydrophobic species. The results suggest that the S-layers of oral anaerobic bacteria may be important determinants of cell surface hydrophobicity. The ultrastructure of the capsular layer of both hydrophilic and hydrophobic strains of seven Bacteroides spp., two Porphyromonas spp., E. yurii and W. recta was studied by electron microscopy. While no capsular material was present outside the S-layer of W. recta and E. yurii strains, most other strains had an intensively stained, dense layer of extracellular polymeric substance of varying thicknesses (10-30 nm). In addition, a much thicker sparse capsular layer was observed in some strains. With the exception of B. intermedius and the S-layer species the strains with a thick capsule were more hydrophilic than the strains with little or no extracellular polymeric material. However, also those S-layer strains of B. buccae and W. recta that were lacking a capsule were equally or more hydrophilic than the PMNLs. Fimbriae of P. gingivalis did not seem to be important determinants of cell surface hydrophobicity.
Clinical Neurophysiology, 2014
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 20, 1991
Mitochondrial myopathy can be caused by several metabolic defects in the mitochondria. Cells with... more Mitochondrial myopathy can be caused by several metabolic defects in the mitochondria. Cells with high levels of oxidative metabolism, such as skeletal muscle, myocardium and brain cells, are particularly vulnerable to these defects. We describe the structural changes in muscle biopsies from 49 patients with mitochondrial myopathy. The younger patients were often symptom-free, but the possibility of a genetic defect was suggested by the family history. "Ragged-red fibres" were found in 10% of the biopsies. Typical paracrystalline inclusions were seen in the mitochondria of the oldest patients. Electron-lucent matrix and increased thickness of the inner membranes of the mitochondria in particular were found in the younger patients. Disorganization of cristae, with cristolysis and unfolding of the cristae was also found. We suggest that structural mitochondrial changes in mitochondrial myopathy constitute a stepwise process and that the mitochondrial alterations of the crist...
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 10, 2001
Skin biopsy for quantification of intraepidermal nerve fibre density has recently been introduced... more Skin biopsy for quantification of intraepidermal nerve fibre density has recently been introduced as a method for diagnosis of peripheral neuropathies. Immunostaining by antibody to protein gene product 9.5 has proved particularly useful because it selectively visualizes the epidermal nerve fibres. We describe the procedure on the basis of relevant literature and our own experience. Results from investigations of 56 healthy individuals and three patients with small fibre involvement as part of their neuropathy are presented. In the healthy individuals, the mean density of epidermal fibres was 12.4 (SD 4.6), median 11.3 and range 6.0-26.1. Three patients with small fibre neuropathy had low intraepidermal nerve fibre density. Skin biopsy for determination of intraepidermal nerve fibre density is a simple and non-painful procedure. Skin biopsies can be done repeatedly and may be used for the purpose of monitoring potential therapeutic agents.
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 20, 2001
Transmission electron microscopy (TEM) is an important diagnostic tool in surgical pathology. We ... more Transmission electron microscopy (TEM) is an important diagnostic tool in surgical pathology. We give an overview, based on our own experience, of the application of TEM in diagnostic pathology. In spite of its potential for high-grade resolution, the actual use of TEM in diagnostic pathology is rather limited. TEM is mandatory in the examination of kidney and muscle biopsies and is often indicated when a metabolic disease is suspected. However, in many centres its importance in tumour pathology has declined because of the advances in the field of immunohistochemistry. TEM requires a great deal of resources and high levels of skills in tissue processing and diagnostic interpretation. The TEM diagnosis must be integrated with light microscopical and, often, immunohistopathological findings, as well as with the clinical data. We therefore recommend close collaboration between the clinician and the laboratory with regard to biopsy indication, handling of samples, and the final diagnosis.
Human reproduction (Oxford, England), 1993
Mitochondrial dysfunction reduces aerobic energy production and results in symptoms from various ... more Mitochondrial dysfunction reduces aerobic energy production and results in symptoms from various tissues, depending on metabolic demands. Mitochondrial adenosine triphosphate (ATP) is essential for sperm motility. Sperm motility was investigated in a patient with a mitochondrial disease caused by reduced activity of the mitochondrial enzyme complexes I and IV, and in two control subjects. Spermatozoa were cultured in media containing various energy substrates. Motility was judged by light microscopy, and ultrastructure by transmission electron microscopy. In the patient with mitochondrial disease, 12% of the spermatozoa were motile in the medium containing only glucose. There was a three-fold increase in motile spermatozoa when pyruvate and succinate were present together with glucose. In contrast, the spermatozoa of both control subjects had best motility in the presence of substrates for complex I, and no further increase was observed when succinate was added. Glucose and pyruvate...
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 20, 1994
In this review we describe surgical methods for open muscle biopsy. In order to obtain optimal ti... more In this review we describe surgical methods for open muscle biopsy. In order to obtain optimal tissue quality, correct handling of the muscle specimens at all stages of the procedure is essential. A technologist who is familiar with the procedure should be present in the operating room. This is important to ensure that specimens for histochemical or biochemical studies are frozen immediately and specimens for electron microscopy are fixed without delay. We describe procedures for processing the specimens for cryostat sections, paraffin sections and electron microscopy, and a simple method for handling muscle specimens in local hospitals before transfer to a hospital with a neuropathological service.
Progress in clinical and biological research, 1989
1. Prog Clin Biol Res. 1989;306:129-33. Maternal inheritance in a family with mitochondrial encep... more 1. Prog Clin Biol Res. 1989;306:129-33. Maternal inheritance in a family with mitochondrial encephalomyopathy. Torbergsen T, Borud O, Mathiesen E, Lindal S, Gustavson KH. Department of Neurology, University Hospital, Tromsø University, Norway. ...
PLoS ONE, 2011
Limb-Girdle Muscular Dystrophy type 2I (LGMD2I) is an inheritable autosomal, recessive disorder c... more Limb-Girdle Muscular Dystrophy type 2I (LGMD2I) is an inheritable autosomal, recessive disorder caused by mutations in the FuKutin-Related Protein (FKRP) gene (FKRP) located on chromosome 19 (19q13.3). Mutations in FKRP are also associated with Congenital Muscular Dystrophy (MDC1C), Walker-Warburg Syndrome (WWS) and Muscle Eye Brain disease (MEB). These four disorders share in common an incomplete/aberrant O-glycosylation of the membrane/extracellular matrix (ECM) protein a-dystroglycan. However, further knowledge on the FKRP structure and biological function is lacking, and its intracellular location is controversial. Based on immunogold electron microscopy of human skeletal muscle sections we demonstrate that FKRP co-localises with the middle-to-trans-Golgi marker MG160, between the myofibrils in human rectus femoris muscle fibres. Chemical cross-linking experiments followed by pairwise yeast 2-hybrid experiments, and co-immune precipitation, demonstrate that FKRP can exist as homodimers as well as in large multimeric protein complexes when expressed in cell culture. The FKRP homodimer is kept together by a disulfide bridge provided by the most N-terminal cysteine, Cys6. FKRP contains N-glycan of high mannose and/or hybrid type; however, FKRP N-glycosylation is not required for FKRP homodimer or multimer formation. We propose a model for FKRP which is consistent with that of a Golgi resident type II transmembrane protein. Citation: Alhamidi M, Kjeldsen Buvang E, Fagerheim T, Brox V, Lindal S, et al. (2011) Fukutin-Related Protein Resides in the Golgi Cisternae of Skeletal Muscle Fibres and Forms Disulfide-Linked Homodimers via an N-Terminal Interaction. PLoS ONE 6(8): e22968.
Neuromuscular Disorders, 2014
Cardiovascular Toxicology, 2010
To examine the response to chronic high-dose angiotensin II (Ang II) and a proposed milder respon... more To examine the response to chronic high-dose angiotensin II (Ang II) and a proposed milder response in female hearts with respect to gene expression and ischemic injury. Female and male litter-matched rats were treated with 400 ng kg -1 min -1 Ang II for 14 days. Hearts were isolated, subjected to 30-min ischemia and 30-min reperfusion in combination with functional monitoring and thereafter harvested for gene expression, WB and histology. Ang II-treated hearts showed signs of non-hypertrophic remodeling and had significantly higher end diastolic pressure after reperfusion, but no significant gender difference was detected. Ang II increased expression of genes related to heart function (ANF, b-MCH, Ankrd-1, PKC-a, PKC-d TNF-a); fibrosis (Col I-a1, Col III-a1, Fn-1, Timp1) and apoptosis (P53, Casp-3) without changing heart weight but with 68% increase in collagen content. High (sub-toxic) dose of Ang II resulted in marked heart remodeling and diastolic dysfunction after ischemia without significant myocyte hypertrophy or ventricular chamber dilatation. Although there were some gender-dependent differences in gene expression, female gender did not protect against the overall response.
Upsala Journal of Medical Sciences, 2009
Muscle biopsy is an important diagnostic tool in the investigation of children with neuromuscular... more Muscle biopsy is an important diagnostic tool in the investigation of children with neuromuscular disorders. This report presents the experience with paediatric muscle biopsies during a 5-year period at a routine pathology laboratory. A total number of 58 cases were included, and indications, microscopical findings, and final histopathological diagnoses were recorded. A total of 21 biopsies were from females (36%) and 37 biopsies from males (64%); 53% of the cases were from children under 2 years of age. Major pathological findings were found in 30% comprising muscular dystrophy, neurogenic atrophy, and congenital and metabolic disorders, even in cases with vague clinical manifestations. These findings confirm the high diagnostic yield of muscle biopsies, especially as new techniques have been introduced such as immunohistochemistry. Muscle pathology is difficult and emphasizes the importance of this service being undertaken by specialized laboratories with an experienced staff. Microscopical examination of muscle biopsies should be based on adequate clinical information, demonstrating the necessity of close contact between pathologists and referring physicians.
Ultrastructural Pathology, 1992
From 1986 to 1991, 472 muscle biopsy specimens from patients from different hospitals in Norway w... more From 1986 to 1991, 472 muscle biopsy specimens from patients from different hospitals in Norway were examined. Of these, 364 were embedded for electron microscopy, and 194 were examined with electron microscopy. Ultrastructural alterations in the mitochondria were detected in 49 of these specimens. Characteristic electron microscopic findings included subsarcolemmal accumulation of abnormal mitochondria of various shapes and sizes, often containing electron-dense granules and sometimes lipid vacuoles in the mitochondria and diffusely electron-lucent matrix space. Paracrystalline inclusion bodies were seldom seen in specimens from young patients, but in some cases mitochondrial electron-dense granules at the cristae were found. These amorphous densities are consistent with lipoproteins, suggesting that they may represent an early stage of paracrystalline inclusions. Biochemical and genetic exploration of the patients with biopsy specimens suggesting mitochondrial disease indicated maternally genetic inheritance and an enzyme defect in the respiratory chain in 21 patients in two families. Three patients had MELAS syndrome, 7 Marinesco-Sjögren syndrome, and 2 Kearns-Sayre syndrome. Five family members had ptosis, cardiomyopathy, mild myopathy, and increased lactate in cerebrospinal fluid and serum. In addition to the diseases mentioned above, changes in the mitochondria were detected in other conditions such as Rett's syndrome (n = 1), ornithine transcarbamylase deficiency (n = 2), and hypothyroidism (n = 2) as well as in 3 patients with clinical and laboratory results indicative of inflammatory myopathy and 3 patients with clinical and laboratory findings consistent with peripheral neuropathy. It is concluded that, although ultrastructural changes in the mitochondria may represent unspecific findings, electron microscopic examination of muscle biopsy specimens is a useful screening method to select specimens for further biochemical analysis and to obtain an early and more precise diagnosis of the disease.
Ultrastructural Pathology, 2010
In this study cerebral ultrastructure was examined in an in vivo rat model, after rewarming from ... more In this study cerebral ultrastructure was examined in an in vivo rat model, after rewarming from profound hypothermia (15-13 degrees C). Animals held at 37 degrees C served as controls. After rewarming, brains were examined by electron microscope. Micrographs were taken randomly, analyzed anonymously, and quantified by morphometry. Serum analysis of the stress marker S-100beta was carried out in identical groups. The most striking findings in rewarmed animals, when compared to controls, were alterations of myelin sheaths (p<.008) and elevated S-100beta (p<.0001). This indicates that cells in the central nervous system are susceptible to injury in an experimental model of accidental hypothermia and rewarming.