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Biomedical subjects

E Andersson

Publications and source records attributed to E Andersson.

At least 19 recordsLinked to original sources

Development of the mesencephalic dopaminergic neuron system is compromised in the absence of neurogenin 2.

Neurogenin 2 (Ngn2) is a proneural gene involved in neuronal differentiation and subtype specification in various regions of the nervous system. In the ventral midbrain, Ngn2 is expressed in a spatiotemporal pattern that correlates with the generation of mesencephalic dopaminergic (mesDA) neurons. We show here that lack of Ngn2 impairs the development of mesDA neurons, such that less than half of the normal mesDA neuron number remain in Ngn2 mutant mice at postnatal stages. Analysis of Ngn2 mutant mice during mesDA neurogenesis show that medially located precursors are formed but are arrested in their differentiation at a stage when they have not yet acquired the characteristics of mesDA neuron precursors. Loss of Ngn2 function appears to specifically affect the generation of DA neurons, as the development of other types of neurons within the ventral midbrain is unaltered. Ngn2 is the first example of a gene expressed in progenitors in the ventricular zone of the mesDA neuron domain that is essential for proper mesDA neuron differentiation, and whose loss of function causes impaired mesDA neurogenesis without other major abnormalities in the ventral midbrain.

Animals↗

Incidence of asthma among workers exposed to sulphur dioxide and other irritant gases.

The aim of the present study was to investigate whether repeated peak exposure (gassings) to sulphur dioxide (SO2) and other irritant gases increases the risk of new-onset asthma. A questionnaire was sent to 4,112 sulphite workers, of whom 1,919 completed the questionnaire and 396 completed the short-form questionnaire, which was sent out as a last reminder. A sample of 130 nonrespondents completed a telephone interview using the short-form questionnaire. The incidence of adult-onset, physician-diagnosed asthma during employment duration was analysed in relation to exposure to SO2 and gassings giving rise to respiratory symptoms. Incidence rates, as well as incidence rate ratios with 95% confidence interval (CI), were calculated. Further Cox regression models were used allowing assessment of hazard ratios (HR) stratified for sex and adjusted for atopy, smoking habits and age. The incidence rate for asthma among sulphite mill workers reporting gassings of SO2 was 6.2 out of 1,000 person-yrs, compared with 1.9 out of 1,000 person-yrs among subjects unexposed to SO2 and any gassings (HR (95% CI) 4.0 (2.1-7.7)). Among males reporting gassings to SO2, the HR (95% CI) for asthma was 5.8 (2.6-13) compared with unexposed males. In conclusion, repeated peak exposure to sulphur dioxide increased the incidence of asthma during work in sulphite pulp mills, which supports the hypothesis of irritant-induced asthma.

Adolescent↗

Patients' experiences of living with peripheral arterial disease awaiting intervention: a qualitative study.

The aim of this study was to investigate patients' experiences of living with peripheral arterial disease (PAD) and the influence on activities of daily living. Twenty-four patients with various degrees of PAD were interviewed. The transcribed texts were analysed using manifest and latent content analysis. Living with PAD meant carrying a hard-to-bear physical, social and emotional burden, and struggling for relief. The experience of burden was interpreted in the following themes representing consequences and strategies for gaining control in daily life: (I) "being limited by the burden" (II) "striving to relieve the burden" (III) "accepting and adapting to the feeling of burden". The use of different coping strategies was crucial to achieve some relief. Pain and sleep disturbance emerged as a major feature of living with PAD, and by combining both analgesics and non-pharmacological methods some pain relief was received. To provide optimal alleviation of pain for these patients, education about pain and pain management is of great importance followed by regular evaluations of the pain and pain management. Furthermore, the study underlines the importance of preventing the progression of the vascular disease and from the individual power and knowledge support and preserve as independent life as possible.

Activities of Daily Living↗

Nitric oxide induces endometrial secretion at implantation time.

BACKGROUND: Uterine cervical secretory cells receive a sympathetic cholinergic secretomotor innervation. Glandular nitric oxide (NO) production has been proposed to be a prerequisite for muscarine-induced carbohydrate secretion from endometrial glands and cervical glands at ovulation time and from the seminal vesicle glands. Nitric oxide has also been suggested to have a significant role in the process of implantation and early pregnancy in the mouse, a process, which has also been compared with an inflammatory response. METHODS: The carbohydrate secretion from everted guinea pig uterine horns placed in organ baths was estimated. Polymerase chain reaction was performed in order to identify the isoforms of nitric oxide synthase (NOS). results. Carbamylcholine chloride (Carbachol) induced carbohydrate secretion of the endometrium, whereas L-NNA and L-NAME inhibited the Carbachol-induced secretion. The isomer D-NAME had no effect on Carbachol-induced secretion. The NO donor GTN induced carbohydrate secretion of the endometrium. The addition of the nitrergic inhibitor of soluble guanylyl cyclase (sGC) ODQ to Carbachol and to the NO donor GTN gave a reduced response. No synergism was seen when the sGC stimulator YC-1 was applied together with Carbachol. Three isoforms of NOS - endothelial NOS (eNOS), cytokine-inducible NOS (iNOS), and neuronal (nNOS) - were identified at implantation time and may take place in the endometrial cell. CONCLUSIONS: The results of this study suggest that glandular NO production is a prerequisite for the autonomic nervous modulation of endometrial secretion in the guinea pig and that NO may play a role in the implantation time.

Animals↗

Estrogen receptor beta is expressed in human embryonic brain cells and is regulated by 17beta-estradiol.

In order to study estrogen effects on developing human neurons, we have established primary cultures of neurons and glia from 8-13-week human embryo cortex and spinal cord. The neuronal identity of the cultures was verified using the neuronal synaptic vesicle and neuronal endosomal membrane markers synaptotagmin, synapsin and synaptophysin, and the glial contribution to the mixed glial-neuronal cultures was verified using the glial marker glial fibrillary acidic protein (GFAP). We here report expression of estrogen receptor beta (ERbeta) in these cells using RT-PCR and sequencing, RNAse protection assay, immunohistochemistry and immunoblotting. We found that both neuronal and mixed glial-neuronal cultures expressed ERbeta. Treatment with 17beta-estradiol gave an increased expression of ERbeta in both types of cultures. These results suggest that ERbeta is expressed in fetal brain and thus may mediate effects of estrogen in the developing nervous system. Furthermore, the results suggest that expression of ERbeta in fetal brain may be regulated by estrogen.

Calcium-Binding Proteins↗

Prevalence of asthma and exhaled nitric oxide are increased in bleachery workers exposed to ozone.

The aims of the present study were to determine whether exposure to high peaks of ozone resulted in an increased prevalence of asthma or respiratory symptoms among bleachery workers and whether nitric oxide (NO) was elevated in the exhaled air of these workers. Bleachery workers (n=228) from three Swedish pulp mills who had been exposed to ozone, together with 63 unexposed control subjects, were investigated by means of spirometry, Phadiatop, exhaled and nasal NO and answers to a questionnaire concerning respiratory symptoms and exposure. Exposure to an ozone peak that gave rise to respiratory symptoms was defined as a "gassing". Bleachery workers reporting four or more gassings involving ozone had an increased prevalence of adult-onset asthma, wheeze, and current asthma symptoms. They also had a higher median concentration of exhaled NO in comparison with those who reported no such gassings (19.2 versus 15.7 parts per billion). No such associations were found in respect of nasal NO. The results from this study show that bleachery workers who have been repeatedly exposed to ozone gassings have an increased prevalence of adult-onset asthma. The results also indicate exhaled nitric oxide may be a marker of airway inflammation in bleachery workers who have been exposed to high peaks of ozone.

Adult↗

The dynamics of social-ecological systems in urban landscapes: Stockholm and the National Urban Park, Sweden.

This study addresses social-ecological dynamics in the greater metropolitan area of Stockholm County, Sweden, with special focus on the National Urban Park (NUP). It is part of the Millennium Ecosystem Assessment (MA) and has the following specific objectives: (1) to provide scientific information on biodiversity patterns, ecosystem dynamics, and ecosystem services generated; (2) to map interplay between actors and institutions involved in management of ecosystem services; and (3) to identify strategies for strengthening social-ecological resilience. The green areas in Stockholm County deliver numerous ecosystem services, for example, air filtration, regulation of microclimate, noise reduction, surface water drainage, recreational and cultural values, nutrient retention, and pollination and seed dispersal. Recreation is among the most important services and NUP, for example, has more than 15 million visitors per year. More than 65 organizations representing 175,000 members are involved in management of ecosystem services. However, because of population increase and urban growth during the last three decades, the region displays a quite dramatic loss of green areas and biodiversity. An important future focus is how management may reduce increasing isolation of urban green areas and enhance connectivity. Comanagement should be considered where locally managed green space may function as buffer zones and for management of weak links that connect larger green areas; for example, there are three such areas around NUP identified. Preliminary results indicate that areas of informal management represent centers on which to base adaptive comanagement, with the potential to strengthen biodiversity management and resilience in the landscape.

City Planning↗

Acute phase response in acute pancreatitis: a comparison with abdominal sepsis.

BACKGROUND: Increased knowledge on the underlying pathophysiological mechanisms in acute pancreatitis (AP) and abdominal sepsis (AS) is essential, not least for the development of novel ways of treatment. The present study aims at determining dynamic changes in the systemic inflammatory response in AP and AS. METHODS: AP was induced by the intraductal injection of sodium taurodeoxycholate in the rat, while AS was induced by caecal ligation and puncture. The animals were killed 1, 3, 6 and 9 h after challenge. Plasma exudation of radiolabelled albumin, myeloperoxidase (MPO), TNF-alpha, MCP-1, superoxide and hydrogen peroxide was measured. RESULTS: Leakage index of human serum albumin showed a significant increase early (I h) after induction of AP and later (9h) in AS compared to controls (P < 0.05). Hydrogen peroxide generation by circulating monocytes/macrophages was high early (1 h) in AP and after 3 and 6h in AS. Superoxide generation increased by time after both challenges. MPO activity increased significantly, starting at 3 h in both AP and AS (P < 0.05). TNF-alpha increased significantly at 6 and 9 h in both models. CONCLUSION: Our results indicate differences in the release of systemic inflammatory mediators and cellular response in AP and AS. However, potential similarities in end-effect, such as the development of remote organ injury (lungs), may exist as implied by the MPO results. Further investigations of the mechanisms are crucial.

Abdomen↗

Effects of nitric oxide donors and inhibitors of nitric oxide signalling on endothelin- and serotonin-induced contractions in human placental arteries.

In order to explore the role of nitric oxide (NO) in the control of fetoplacental vascular tone in normal pregnancy we have examined the effects of NO donors on uteroplacental arteries pre-contracted with the vasoconstrictor endothelin-1 (ET-1) or serotonin (5-HT). We have furthermore examined the effects of guanylate cyclase inhibitors on the NO-induced relaxation. Segments of placental arteries (n=102) obtained from 39 placentas immediately after delivery were mounted in organ baths and superfused with Krebs-Ringer solution at 37 degrees C. The vessel segments were exposed to drugs for various intervals and the tension was recorded isometrically and registered on a polygraph. Cyclic guanosine monophosphate (cGMP) analysis was performed after extraction of vessel segments using a specific radioimmunoassay. The placental artery segments responded to ET-1 and 5-HT with a dose-dependent vasoconstriction. After pre-contraction with ET-1 (10(-7) M) or 5-HT (10(-6) M), the vessels relaxed in response to the NO donors glyceryltrinitrate (GTN) (10(-6) M) and S-nitroso-N-acetyl-penicillamine (SNAP) (10(-5) M). In the presence of the non-specific guanylate cyclase inhibitor LY 83583 (10(-6) M), the vessels responded with a small contraction. In the presence of the soluble guanylate cyclase (sGC) inhibitor 1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) the non-treated vessels responded with a relaxation. 1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one gave no obvious relaxation in pre-contracted vessels. Addition of 8-Br-cGMP, the cell-permeant analogue of cGMP, with or without pre-contraction had no effect on the vessels. Cyclic guanosine monophosphate analysis showed that GTN treatment caused an increase in cGMP after 12 min. Our results indicate that NO acts as a vasodilator in placental vessels. The cGMP-dependent mechanisms may be involved in NO-induced relaxation but cGMP-independent mechanisms appear also to be involved.

Adult↗

Isolation of human cationic antimicrobial protein-18 from seminal plasma and its association with prostasomes.

BACKGROUND: Cathelicidins are a group of antibiotic peptides with broad antimicrobial activity. They are considered to be an essential part of the innate immune system. The only known human cathelicidin is the human cationic antimicrobial protein (hCAP-18), from which the antimicrobial peptide LL-37 is released. METHODS AND RESULTS: In the present study, we purified hCAP-18 from seminal plasma and confirmed its identity by N-terminal amino acid sequencing. Gel filtration of seminal plasma showed the presence of hCAP-18 in both a low and a high molecular weight peak. Fractions corresponding to the high molecular form of hCAP-18 also contained dipeptidyl peptidase IV (CD26), a prostasome marker. This finding suggested that hCAP-18 found in fractions corresponding to high molecular weight molecules, is prostasome-associated. Flow cytometry confirmed the association of hCAP-18 with prostasomes and indicated that the molecule is surface bound. Western blot showed the presence of intact hCAP-18 in sperm, prostasomes and ultracentrifuged seminal plasma. CONCLUSIONS: These findings suggest that hCAP-18 may have an important role in antimicrobial defence during human reproduction. The binding of hCAP-18 to prostasomes indicates that protasomes can serve as a reservoir of this precursor of the antibiotic peptide LL-37.

Antimicrobial Cationic Peptides↗

Proliferation of primitive myeloid progenitors can be reversibly induced by HOXA10.

Recent studies show that several Hox transcription factors are important for regulation of proliferation and differentiation in hematopoiesis. Among these is H0XA10, which is selectively expressed at high levels in the most primitive subpopulation of human CD34(+) bone marrow cells. When overexpressed, H0XA10 increases the proliferation of early progenitor cells and can lead to the development of myeloid leukemia. To study the effects of H0XA10 on primitive hematopoietic progenitors in more detail, transgenic mice were generated with regulatable H0XA10 expression. The transgenic mouse model, referred to as tetO-HOXA10, contains the H0XA10 gene controlled by a tetracycline-responsive element and a minimal promoter. Thus, the expression of H0XA10 is inducible and reversible depending on the absence or presence of tetracycline or its analog, doxycycline. A retroviral vector containing the tetracycline transactivator gene (tTA) was used to induce expression of the H0XA10 gene in bone marrow cells from the transgenic mice. Reverse transcription-polymerase chain reaction analysis confirmed regulatable H0XA10 expression in several transgenic lines. H0XA10 induction led to the formation of hematopoietic colonies containing blastlike cells and megakaryocytes. Moreover, the induction of H0XA10 resulted in significant proliferative advantage of primitive hematopoietic progenitors (spleen colony-forming units [CFU-S(12)]), which was reversible on withdrawal of induction. Activation of H0XA10 expression in tet0-H0XA10 mice will therefore govern proliferation of primitive myeloid progenitors in a regulated fashion. This novel animal model can be used to identify the target genes of HOXA10 and better clarify the specific role of HOXA10 in normal and malignant hematopoiesis.

Animals↗

Intramuscular myoelectric activity and selective coactivation of trunk muscles during lateral flexion with and without load.

STUDY DESIGN: Myoelectric activity of trunk muscles was measured intramuscularly in six healthy subjects as they maintained static trunk postures at 0 degrees, 15 degrees, and 30 degrees of lateral bending, unloaded or holding a 20-kg load in one hand alongside the body. OBJECTIVE: To determine the position and load dependency of the agonistic and antagonistic myoelectric responses of deep and superficial trunk lateral flexor muscles. SUMMARY OF BACKGROUND DATA: Loading of the trunk in lateral bending is associated with incidences of low back pain. The neuromotor control of muscles surrounding the spine may be decisive for its vulnerability. Earlier documentation of the activation pattern of trunk muscles, particularly those situated deeply, is incomplete. METHODS: Trunk angle was measured between S1-C7 and the vertical with a protractor. Electromyographic activity was recorded unilaterally from eight trunk muscles using intramuscular fine-wire electrodes inserted under the guidance of ultrasound. RESULTS: The electromyographic data showed that all muscles on the side contralateral to the load, except rectus abdominis, had their highest activity while loaded in the position most laterally flexed to the loaded side. The degree of bilateral coactivation was greater for the ventral than for the dorsal muscles. CONCLUSIONS: The myoelectric responses of most lumbar trunk muscles to static lateral flexion were dependent on trunk position and loading. The abdominal muscles demonstrated more coactivation than the other trunk muscles, and thus appeared to contribute more to trunk stabilization in laterally bent and loaded trunk positions.

Abdomen↗

[Residential care after the geriatric care reform. District nurses experience extensive responsibility and limited rights].

We studied the care of patients in homes for the elderly and in special homes for the demented in the city of Malmö. Nine district nurses were interviewed using a tape recorder, and the content of the interviews was analyzed. Many patients needed extensive care, and resources were insufficient regarding both number of staff and their competence. The management of nursing in the various districts of the city was not well-defined. More consulting time was requested on the part of both district nurses and general practitioners in homes for the elderly and homes for the demented.

Aged↗

[CSF-analyses in clinical diagnosis of Creutzfeldt-Jakob disease. A literature review and three cases from routine clinical practice].

The clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is often difficult, since the clinical presentation varies between patients and is often uncharacteristic. Therefore, CJD is often not suspected until late in the disease process, due to the rapid progress of the disease. Suspected CJD is, however, frequent in routine clinical practice, in the investigation of patients with rapidly progressing dementia and/or uncharacteristic neurological symptoms. We present results from cerebrospinal fluid (CSF) analyses in CJD, focusing on the two neuron-specific proteins 14-3-3 and tau. Analysis of 14-3-3 protein is performed by Western blotting, in which 14-3-3 is either detectable in CSF or not, while CSF-tau is analyzed using quantitative ELISA methodology, in which a markedly increased CSF level of tau (< 1500 pg/mL) is indicative of CJD. Tau and 14-3-3 findings show comparable sensitivity and specificity, higher than the presence of spike and wave complexes on an EEG. The increase in CSF-tau in CJD is substantially higher than in Alzheimer's disease, with low overlap between the disorders. Instead, false positive results are found in disorders with massive acute neuronal damage (encephalitis, stroke and CNS tumors). In cases in which these disorders cannot be differentiated from CJD on clinical grounds, they can often be identified by MRT or by the finding of blood-brain barrier damage or signs of inflammation upon CSF analysis. CSF-tau is increasingly used in the routine diagnosis of Alzheimer's disease, and the analysis also seems to be of use in the clinical diagnosis of CJD. We also present three cases from routine clinical practice, all with a marked increase in CSF-tau, which was the only positive objective sign in two of the cases.

Aged↗

Groucho-mediated transcriptional repression establishes progenitor cell pattern and neuronal fate in the ventral neural tube.

The pattern of neuronal specification in the ventral neural tube is controlled by homeodomain transcription factors expressed by neural progenitor cells, but no general logic has emerged to explain how these proteins determine neuronal fate. We show that most of these homeodomain proteins possess a conserved eh1 motif that mediates the recruitment of Gro/TLE corepressors. The eh1 motif underlies the function of these proteins as repressors during neural patterning in vivo. Inhibition of Gro/TLE-mediated repression in vivo results in a deregulation of cell pattern in the neural tube. These results imply that the pattern of neurogenesis in the neural tube is achieved through the spatially controlled repression of transcriptional repressors-a derepression strategy of neuronal fate specification.

Amino Acid Sequence↗

Differential expression of vesicular monoamine transporter (VMAT) 1 and 2 in gastrointestinal endocrine tumours.

Neuroendocrine tumours are characterized by their capacity to produce hormones, which are stored in vesicles and secretory granules. Demonstration of granule/vesicle proteins in tumours is taken as evidence of neuroendocrine differentiation. Vesicular monoamine transporters (VMAT1 and VMAT2) mediate the transport of amines into vesicles of neurons and endocrine cells. The expression of VMAT1 and VMAT2 and the usefulness of VMAT1 and VMAT2 in the histopathological diagnosis of gastrointestinal endocrine tumours have not been fully explored. This study therefore investigated the expression of VMAT1 and VMAT2 in 211 human gastrointestinal tumours by immunocytochemistry and western blotting. VMAT1 and/or VMAT2 were demonstrated in the majority of amine-producing endocrine tumours of gastric, ileal, and appendiceal origin. Serotonin-producing endocrine tumours (ileal and appendiceal carcinoids) expressed predominantly VMAT1, while histamine-producing endocrine tumours (gastric carcinoids) expressed VMAT2 almost exclusively. In peptide-producing endocrine tumours such as rectal carcinoids and endocrine pancreatic tumours, only a small number of immunopositive tumour cells were observed. No labelling was found in non-endocrine tumours, including gastric, colorectal and pancreatic adenocarcinomas and gastrointestinal stromal tumours. In conclusion, VMAT1 and VMAT2 are differentially expressed by gastrointestinal endocrine tumours, with a pattern specific for each tumour type, reflecting their neuroendocrine differentiation and origin. VMAT1 and VMAT2 may therefore become valuable markers in the classification of neuroendocrine tumours and may also indicate patients suitable for radioisotope treatment operating via these transporter systems.

Blotting, Western↗

Three forms of GnRH in the brain and pituitary of the turbot, Scophthalmus maximus: immunological characterization and seasonal variation.

Three forms of GnRH, chicken (c) GnRH-II, salmon (s) and seabream (sb) GnRH, were immunologically characterized in the brain and pituitary of turbot by ELISA. cGnRH-II and sGnRH were detected in the brain, while sbGnRH and sGnRH (but not cGnRH-II) were detected in the pituitary. In females, the levels of cGnRH-II in the turbot brain extracts increased from May to July, concomitant with an increase in oocyte diameter. In the pituitary, sbGnRH was found to be the dominant form, with levels 100-600-fold those of sGnRH. Both sGnRH and sbGnRH in the pituitary showed variation during the spawning season; sbGnRH increased from May to July and correlated with the increase in oocyte diameter, while sGnRH decreased. The overall patterns were the same for male turbot, although levels were generally lower. These findings suggest that sbGnRH could be controlling reproduction in the turbot. However, the seasonal variation in sGnRH indicates a potential physiological role in turbot reproduction. This study gives the first immunological indications that sbGnRH is present in the pituitary of a pleuronectiform fish, and will provide the basis for further studies on the endocrine regulation of reproduction in flatfish.

Animals↗