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Biomedical subjects

O Johansson

Publications and source records attributed to O Johansson.

At least 19 recordsLinked to original sources

Expression of oestrogen receptor alpha and beta is higher in skeletal muscle of highly endurance-trained than of moderately active men.

AIM: Two known oestrogen receptors (ERs), ERalpha and the recently cloned ERbeta, are expressed in the human skeletal muscle of both males and females. The effects of oestrogen and the role of ERs in skeletal muscle tissue are not well known. Oestrogen receptors and some of their target genes are involved in angiogenic processes. It was hypothesized that ERs are expressed at a higher level in a group with higher oxidative capacity, and that such an enhanced expression would parallel expression of the angiogenic factor -- vascular endothelial growth factor (VEGF). METHOD: Muscle biopsies were taken from vastus lateralis in 10 highly endurance-trained males and 10 moderately active males and analysed for the expression of ERs and VEGF. RESULTS: The major findings in the present study were the higher mRNA levels of ERalpha, ERbeta and VEGF in the highly endurance-trained than in the moderately active group. CONCLUSION: These data suggest that the greater mRNA expression of ERalpha and ERbeta and the oestrogen-associated angiogenic factor VEGF support the hypothesis of an involvement of ERs in the adaptation of skeletal muscle to endurance training.

Adolescent↗

EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy.

Skin biopsy has become a widely used tool to investigate small calibre sensory nerves including somatic unmyelinated intraepidermal nerve fibres (IENF), dermal myelinated nerve fibres, and autonomic nerve fibres in peripheral neuropathies and other conditions. Different techniques for tissue processing and nerve fibre evaluation have been used. In March 2004, a Task Force was set up under the auspices of the European Federation of Neurological Societies (EFNS) with the aim of developing guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathies. We searched the Medline database from 1989, the year of the first publication describing the innervation of human skin using immunostaining with anti-protein-gene-product 9.5 (PGP 9.5) antibodies, to 31 March 2005. All pertinent papers were rated according to the EFNS guidance. The final version of the guidelines was elaborated after consensus amongst members of the Task Force was reached. For diagnostic purposes in peripheral neuropathies, we recommend performing a 3-mm punch skin biopsy at the distal leg and quantifying the linear density of IENF in at least three 50-mum thick sections per biopsy, fixed in 2% PLP or Zamboni's solution, by bright-field immunohistochemistry or immunofluorescence with anti-PGP 9.5 antibodies (level A recommendation). Quantification of IENF density closely correlated with warm and heat-pain threshold, and appeared more sensitive than sensory nerve conduction study and sural nerve biopsy in diagnosing small-fibre sensory neuropathy. Diagnostic efficiency and predictive values of this technique were very high (level A recommendation). Confocal microscopy may be particularly useful to investigate myelinated nerve fibres, dermal receptors and dermal annex innervation. In future, the diagnostic yield of dermal myelinated nerve fibre quantification and of sweat gland innervation should be addressed. Longitudinal studies of IENF density and regeneration rate are warranted to correlate neuropathological changes with progression of neuropathy and to assess the potential usefulness of skin biopsy as an outcome measure in peripheral neuropathy trials (level B recommendation). In conclusion, punch skin biopsy is a safe and reliable technique (level A recommendation). Training in an established cutaneous nerve laboratory is recommended before using skin biopsy as a diagnostic tool in peripheral neuropathies. Quality control at all levels is mandatory.

Biopsy↗

Oestrogen receptor beta is expressed in adult human skeletal muscle both at the mRNA and protein level.

AIM: There are two known oestrogen receptors (ER), oestrogen receptor alpha (ERalpha) and the recently cloned oestrogen receptor beta (ERbeta). ERalpha mRNA has been detected in mouse, rat, bovine and human skeletal muscle. ERbeta mRNA has been detected in bovine skeletal muscle. To our knowledge, no study has investigated the expression of oestrogen receptor beta in human skeletal muscle. Therefore, the primary aim of the present investigation was to study ERbeta mRNA and protein expression in human skeletal muscle. In addition the ERalpha expression was also studied. METHODS: Muscle biopsies were taken from vastus lateralis in six healthy adults (three women and three men). mRNA expression was detected with real-time PCR (TaqMan) and protein localization by immunohistochemistry. RESULTS: A clear expression of ERalpha and ERbeta mRNA was seen in skeletal muscle in all subjects. The ERalpha mRNA expression was 180 fold higher compared with that of ERbeta mRNA. Immunohistochemistry demonstrated positive staining for ERbeta, but not for ERalpha, with localization to the nuclei of skeletal muscle fibres. On average, 70% of all nuclei were ERbeta-positive. CONCLUSION: The present study shows for the first time ERbeta mRNA and protein expression in human skeletal muscle tissue in both males and females.

Adult↗

Identification of functional clusters of transcription factor binding motifs in genome sequences: the MSCAN algorithm.

MOTIVATION: The identification of regulatory control regions within genomes is a major challenge. Studies have demonstrated that regulating regions can be described as locally dense clusters or modules of cis-acting transcription factor binding sites (TFBS). For well-described biological contexts, it is possible to train predictive algorithms to discern novel modules in genome sequences. However, utility of module detection methods has been severely limited by insufficient training data. For only a few tissues can one obtain sufficient numbers of literature-derived regulatory modules. RESULTS: We present a novel method, MSCAN, that circumvents the training data problem by measuring the statistical significance of any non-overlapping combination of TFBS in a window. Given a set of transcription factor binding profiles, a significance threshold, and a genomic sequence, MSCAN returns putative regulatory regions. We assess performance on two curated collections of regulatory regions; one each for tissue-specific expression in liver and skeletal muscle cells. The efficiency of MSCAN allows for predictive screens of entire genomes.

Algorithms↗

Cutaneous mast cells are altered in normal healthy volunteers sitting in front of ordinary TVs/PCs--results from open-field provocation experiments.

BACKGROUND: Considerable controversy has surrounded the question of possible biological responses to electromagnetic fields (EMFs) generated from visual display terminals (VDTs), such as personal computers (PCs) and ordinary television sets (TVs). The cellular and molecular mechanisms for such potential harmful health hazards have not yet been understood, although clues from the literature include mast cells and histamine. The aim of this study was therefore to investigate possible biological mast cell responses to TV/PC screens. METHODS: Using the indirect immunofluorescence technique, we studied the presence of histamine-containing mast cells in the dermis of healthy volunteers. Cutaneous biopsies taken before and after exposure to ordinary TV/PC screens for 2 or 4 h were investigated in 13 healthy subjects. RESULTS: Our present in vivo study indicates that normal cutaneous mast cells could be altered by exposure from ordinary TV/PC screens. To our great surprise, we found the number of mast cells in the papillary and reticular dermis to increase, to varying degrees, in 5 out the 13 subjects after such an exposure. A migration of mast cells towards the uppermost dermis appeared as the most important event. Thus, the normally upper "empty zone" of the dermis disappeared, and instead, a higher density of mast cells were found in this zone. These cells also seemed to have a tendency to increase in number towards the epidermal-dermal junctional zone and some of them lost their granular content and the cytoplasm shrunk (=degranulation). These findings could only be seen in the exposed skin. Two of the 13 cases instead showed a decrease in mast cell number, but the shift in mast cells towards the upper dermis was still visible. Twenty-four h after the provocation, the cellular number and location were normalized in all subjects. CONCLUSIONS: By definition, normal healthy volunteers are assumed not to react to a TV/PC screen provocation. To our great surprise, this proved not to be true. The present results might lay a foundation to understand the underlying cause of so-called "screen dermatitis" with special reference to mast cells. However, blind or double-blind experiments using patients ought to be further investigated in order to find out the exact cause for the observed changes. Such causes include the effects of surrounding airborne chemicals, stress factors, etc.

Adult↗

Histamine immunocytochemistry: a new method for detection of basophils in peripheral blood.

We report that basophils in peripheral blood can be stained using histamine immunocytochemistry. The staining is based on the fixation of leucocytes with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (CDI) and the subsequent incubation of these cells with antisera raised against histamine conjugated to different carrier proteins using CDI. The staining appears to be specific for basophils and stained cells can be examined using both fluorescence microscopy and flow cytometry. In addition, histamine immunocytochemistry can be combined with conventional immunocytochemistry by incubating leucocytes with antibodies to cell surface antigens prior to or following fixation of the cells with CDI. Thus, histamine immunocytochemistry may be a valuable tool in future studies of human basophils.

Alcian Blue↗

Eosinophil cationic protein- and eosinophil-derived neurotoxin/eosinophil protein X-immunoreactive eosinophils in prurigo nodularis.

It is known that eosinophils are actively involved in allergy and inflammation. The granular components of eosinophils, eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin/eosinophil protein X (EDN/EPX), play an important role in such allergic and inflammatory processes. Prurigo nodularis is a chronic inflammatory skin disease with obvious cutaneous nervous involvement. To detect ECP and EDN/ EPX expression in the eosinophils and their relation to nerve fibres in prurigo nodularis, ECP and EDN/EPX single-labelling immunofluorescence, and ECP and PGP 9.5 double-labelling immunofluorescence, were performed. In prurigo nodularis lesional skin, the ECP- and EDN/EPX-containing cells, which were mainly distributed in the upper dermis, were significantly increased in number compared to their numbers in uninvolved and normal skin. The immunoreactivity of ECP and EDN/EPX in prurigo lesional skin was stronger than in uninvolved skin or control skin. The PGP 9.5-immunoreactive nerves were also increased in number in the areas where there were increased eosinophils. The nerves were in close proximity to eosinophils, and occasionally even seemed to be in contact. The present results indicate that the cutaneous nerves and the ECP- and EDN/EPX-containing eosinophils are possibly involved in the pathogenesis of the disease. The close relationship of nerves and eosinophils indicates that the cutaneous nerves may influence eosinophil function in the chronic inflammatory states of prurigo nodularis. ECP and EDN/EPX could thus be released to the local tissue and modulate the inflammation of the prurigo nodularis lesion.

Aged↗

CGRP-immunoreactive nerves in prurigo nodularis--an exploration of neurogenic inflammation.

BACKGROUND: The present study has explored the localization and distribution of calcitonin gene-related peptide (CGRP)-immunoreactive (IR) nerve fibers in prurigo nodularis, especially emphasizing its relationships to mast cells and eosinophils, which all are important contributors to inflammation. METHODS: The exact localization of CGRP in the nerve fibers of prurigo nodularis lesional skin has been clarified by an ultrastructural immunogold labelling technique; and the relationships of CGRP-IR nerve fibers to tryptase-IR mast cells or eosinophil cationic protein (ECP)-IR eosinophils were also investigated by immunofluorescence double-labelling. RESULTS: This ultrastructural study has demonstrated that CGRP immunoreactivity is increased in the dense-core vesicles in the axons of the prurigo nodularis lesional skin; the axons which contain CGRP are, in addition, enlarged and have more dense-core vesicles than the axons which do not contain CGRP. The immunofluorescence investigation demonstrated that tryptase-containing mast cells and ECP-containing eosinophils also are significantly increased in the lesional skin. CONCLUSIONS: The results indicate that certain neurons increasingly express CGRP, which may dynamically result in a neurogenic inflammation in the lesional skin, through vasodilatation, and recruitment and regulation of inflammatory cells, e.g. eosinophils and mast cells.

Aged↗

A theoretical model based upon mast cells and histamine to explain the recently proclaimed sensitivity to electric and/or magnetic fields in humans.

The relationship between exposure to electromagnetic fields (EMFs) and human health is more and more in focus. This is mainly because of the rapid increasing use of such EMFs within our modern society. Exposure to EMFs has been linked to different cancer forms, e.g. leukemia, brain tumors, neurological diseases, such as Alzheimer's disease, asthma and allergy, and recently to the phenomena of 'electrosupersensitivity' and 'screen dermatitis'. There is an increasing number of reports about cutaneous problems as well as symptoms from internal organs, such as the heart, in people exposed to video display terminals (VDTs). These people suffer from subjective and objective skin and mucosa-related symptoms, such as itch, heat sensation, pain, erythema, papules and pustules. In severe cases, people can not, for instance, use VDTs or artificial light at all, or be close to mobile telephones. Mast cells (MCs), when activated, release a spectrum of mediators, among them histamine, which is involved in a variety of biological effects with clinical relevance, e.g. allergic hypersensitivity, itch, edema, local erythema and many types of dermatoses. From the results of recent studies, it is clear that EMFs affect the MC, and also the dendritic cell, population and may degranulate these cells. The release of inflammatory substances, such as histamine, from MCs in the skin results in a local erythema, edema and sensation of itch and pain, and the release of somatostatin from the dendritic cells may give rise to subjective sensations of on-going inflammation and sensitivity to ordinary light. These are, as mentioned, the common symptoms reported from patients suffering from 'electrosupersensitivity'/'screen dermatitis'. MCs are also present in the heart tissue and their localization is of particular relevance to their function. Data from studies made on interactions of EMFs with the cardiac function have demonstrated that highly interesting changes are present in the heart after exposure to EMFs. One could speculate that the cardiac MCs are responsible for these changes due to degranulation after exposure to EMFs. However, it is still not known how, and through which mechanisms, all these different cells are affected by EMFs. In this article, we present a theoretical model, based upon observations on EMFs and their cellular effects, to explain the proclaimed sensitivity to electric and/or magnetic fields in humans.

Electromagnetic Fields↗

Neurochemical and cellular markers in human cervix of late pregnant, postpartal and non-pregnant women.

BACKGROUND: The aim was to evaluate the peptidergic innervation and the dendritic cell content in the cervix uteri. METHODS: Cervical biopsies were obtained from late pregnant (n=5), postpartal (n=5) and non-pregnant (n=5) women. The samples were prepared for immunohistochemistry using antibodies to protein S-100 (S-100), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), human peptide histidine isoleucine amide (PHM 27), neuropeptide tyrosine (NPY), and human histocompatibility complex class II subregion DR (HLA-DR). RESULTS: Nerve fibers positive for protein S-100, and dendritic cells positive for S-100 and HLA-DR were abundant in the cervix, especially at late pregnancy. CGRP, VIP, PHM-27 and NPY positive nerve fibers were present in non-pregnant, short nerve fibers and scattered immunoreactivity at term, and further scattered immunoreactivity after parturition. NPY positive nerve fibers were decreased at term, and after parturition a scattered immunoreactivity was observed. CONCLUSIONS: The abundant protein S-100 positive nerve fibers implies an impact of myelinated nerves in the cervix uteri during pregnancy. The abundant dendritic cells, positive for HLA-DR and S-100, especially at term, indicates a general activation of the immune system until late pregnancy and parturition. The changed occurrence and distribution of immunoreactivity for CGRP, VIP and PHM-27 suggest a release of these neuropeptides until term. The changes in NPY immunoreactivity indicate a release of NPY around parturition.

Adult↗

Endogenous prostaglandins are physiological regulators of endocrine cells in the gastroduodenal mucosa of the rat.

BACKGROUND/AIM: To investigate whether endogenous prostaglandins participate in the regulation of the gastrointestinal endocrine cell system. METHODS: Sprague-Dawley rats were treated with 1 mg/kg indomethacin subcutaneously or indomethacin subcutaneously and 500 microg/kg oral prostaglandin E2 or solvents for 2 months. Endocrine cells were visualized by using immunohistochemistry and by the Sevier-Munger silver stain on specimens from the gastroduodenal mucosa, and their total volume was estimated, using standard stereological methods. Plasma and gastrointestinal tissue concentrations of regulatory peptides were analyzed by radioimmunoassay. RESULTS: Fundic mucosa. The total volume of cells stained with the Sevier-Munger silver stain (enterochromaffin-like) was increased by indomethacin, but reduced by the administration of prostaglandin E2 (P < 0.05 vs. indomethacin). Indomethacin increased the total volume of somatostatin-immunoreactive. Similarly, rats given indomethacin and prostaglandin E2 had higher values than controls. Indomethacin increased the tissue concentration of somatostatin in the gastric fundus whereas prostaglandin E2 prevented such changes (P < 0.05 vs. indomethacin). Antral mucosa. The total volume of serotonin-immunoreactive cells was reduced by indomethacin, but increased by prostaglandin E2 (P < 0.05 vs. controls and indomethacin, respectively). Duodenal mucosa. The total volume of somatostatin-immunoreactive cells was reduced in the rats given indomethacin and prostaglandin E2 (P < 0.05 vs. controls and indomethacin). Indomethacin reduced and simultaneous administration of prostaglandin E2 increased the total volume of CCK-immunoreactive cells (P < 0.05 vs. controls and indomethacin). Indomethacin reduced the total volume of serotonin-immunoreactive cells whereas the simultaneous administration of PGE2 comparatively increased their total volumes (P < 0.05 vs. indomethacin), although they were still lower than the control values. The total volume of GIP-immunoreactive cells was slightly increased in the rats given both indomethacin and indomethacin + prostaglandin E2. The tissue concentration of somatostatin in the duodenum was reduced in rats given indometacin and prostaglandin E2 (P < 0.05 vs. controls and indomethacin). CONCLUSION: Endogenous prostaglandins, particularly prostaglandin E2, regulate CCK-, enterochromaffin-like-, somatostatin-, GIP- and enterochromaffin cells in the gastroduodenal mucosa of the rat.

Administration, Oral↗

Light and electron microscopic immunohistochemical observations of p75 nerve growth factor receptor-immunoreactive dermal nerves in prurigo nodularis.

Prurigo nodularis is an inflammatory skin disease characterized by neurohyperplasia. Neurotrophins and their receptors play a critical role in nerve growth, differentiation, maturation and maintenance, including cutaneous nerve fiber growth and innervation. They may also be responsible for events related to the growth and differentiation control of keratinocytes. To explore the exact distribution of the p75 low-affinity nerve growth factor receptor (p75 NGFr) in the cutaneous nerve components, p75 NGFr immunofluorescence as well as ultrastructural immunohistochemical studies were performed on prurigo nodularis lesional skin and normal human skin samples. The immunofluorescence results revealed that nerve fibers and bundles were increased in number and size in lesional upper dermis with stronger p75 NGFr immunoreactivity than in the corresponding normal tissue. At the ultrastructural level, a lot of nerve fibers clustered together in the prurigo nodularis dermal tissue. The axons were enlarged and branched, but the axons themselves seldom showed any NGFr immunoreactivity. The Schwann cell bodies were extended and irregularly shaped, and tended to separate into many branches enveloping the axons. The Schwann cell membrane showed strong p75 NGFr immunoreactivity. The perineurium cells also revealed strong p75 NGFr immunoreactivity. The Schwann cells inside the perineurium were less p75 NGFr-immunoreactive than those outside the perineurium. The membrane of certain basal keratinocytes showed NGFr immunoreactivity as well. The present results indicate that overexpression of p75 NGFr in Schwann cells and perineurium cells could contribute to the neurohyperplasia in prurigo nodularis.

Aged↗

Serotonin in human allergic contact dermatitis. An immunohistochemical and high-performance liquid chromatographic study.

Allergic contact dermatitis (ACD) is a common clinical condition leading to considerable morbidity. We have recently demonstrated that ketanserin, a serotonin antagonist, significantly inhibits nickel sulphate-induced ACD. Furthermore, serotonin-immunoreactive (IR) cells have previously been demonstrated in normal human cutaneous melanocytes. To further elucidate the role of serotonin in cutaneous contact hypersensitivity, we compared ACD involved skin and uninvolved skin from nickel-allergic patients, and normal skin from healthy volunteers, for the presence of serotonin-like immunoreactive cells using immunohistochemistry. In addition, serotonin concentrations in ACD involved and uninvolved skin were compared by high-performance liquid chromatography (HPLC). In the skin of normal healthy volunteers, the serotonin-IR cells were situated in the basal layer of the epidermis. In uninvolved skin the cells were also situated in the basal layer, but they were more numerous and the immunofluorescence intensity was greater. In involved skin, the IR cells were fewer and they were found higher up in the epidermis. Also, the configuration of these cells was different: they showed enlarged and elongated dendrites as well as dendritic spines. The serotonin antiserum-labelled cells in ACD involved skin were also NKI-beteb positive (the latter is known as a reliable marker of melanocytes). The concentration of serotonin in involved skin was significantly higher than that in uninvolved skin in ACD patients (P < 0.05). Taken together, our previous and present results indicate that serotonin plays an important role in ACD. The basal epidermal serotonin-IR cells are more dendritic in ACD, and are found more superficial in the epidermis, where they might release their content of serotonin, thereby influencing the inflammatory process.

Adult↗

Increased occurrence of PGP 9.5-immunoreactive epidermal Langerhans cells in rat plantar skin after sciatic nerve injury.

This study examines the occurrence and distribution of epidermal dendritic cells (DCs) in cryostate sections from plantar skin in normal rats and in rats with a crush injury or neurotomy and suture of the sciatic nerve. The dendritic cells were visualized with antibodies against protein-gene product 9.5 (PGP 9.5). Counts under the fluorescence microscope showed that the occurrence of dendritic cells is increased and that the proportion of dendritic cells in the basal layer is elevated 3 months after sciatic neurotomy and suture but not after a crush lesion. The countings also revealed that the number of cells is elevated as soon as 1 week after neurotomy and suture. Labelling with specific antibodies showed that the dendritic cells examined represent Langerhans cells (LCs). These observations show that there is a neural influence on the occurrence and distribution of PGP 9.5-immunoreactive epidermal Langerhans cells. Whether this influence is direct or indirect remains to be ascertained.

Animals↗

Indirect effect of sciatic nerve injury on the epidermal thickness of plantar glabrous skin in rats.

In patients with nerve injuries, the skin over the denervated part tends to atrophy. Few experimental studies have dealt with this issue. In this paper we examine the effects of nerve injury on the epidermis in plantar glabrous skin in rats. Analysis of paraffin sections showed that the epidermis becomes abnormally thin after sciatic neurotomy and suture or neurectomy, but not after nerve crush. Autoradiographic analysis showed a subnormal number of thymidine-labelled epidermal cells in plantar skin of rats subjected to sciatic neurectomy. However, after selective division of the sciatic foot branches, with preserved function of thigh and leg muscles, the number of labelled epidermal cells did not differ significantly between the side operated on and the control side. We conclude that the effect of sciatic nerve division on plantar skin in rats is caused by the motor deficiency in the foot rather than by deficient innervation of the skin.

Analysis of Variance↗

Characterization of [3H]substance P binding sites in human skin.

Radioligand binding experiments were performed with crude homogenates from normal human skin in order to investigate substance P receptor density. Binding of [3H]substance P ([3H]SP) reached equilibrium after 20 min and was saturable analysis of saturation curves gave a significantly better fit using two-site binding compared to the single-site model. Competition studies employing some selective agonists for NK1, NK2 and NK3 receptors have demonstrated that only the NK1 selective agonist, [Sar9, Met(O2)11]-SP, was a competitor for [3H]SP binding. In addition, the non-hydrolyzable guanosine 5'-0-(3-thiotriphosphate) altered the dissociation of SP from NK1 receptors by increasing the number of low-affinity sites. These data show that in the skin [3H]SP binds to a single population of substance P high-affinity sites, which represent NK1-type receptors.

Aged↗