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Träfflista för sökning "hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Klinisk medicin) hsv:(Klinisk laboratoriemedicin) "

Sökning: hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Klinisk medicin) hsv:(Klinisk laboratoriemedicin)

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  • Lindahl, Katarina, et al. (författare)
  • Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy
  • 2018
  • Ingår i: Bone. - 8756-3282 .- 1873-2763. ; 114, s. 268-277
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mutations of the endoplasmic reticulum (ER) stress transducer OASIS (encoded by CREB3L1), cause severe recessive osteogenesis imperfecta (OI) not compatible with surviving the neonatal period, as has been shown in two unrelated families through a whole gene deletion vs. a qualitative alteration of OASIS Heterozygous carriers in the described families have exhibited a mild phenotype. OASIS is a transcription factor highly expressed in osteoblasts, and OASIS(-/-) mice exhibit severe osteopenia and spontaneous fractures. Here, we expand the clinical spectrum by a detailed phenotypic characterization of the first case of OASIS-associated OI surviving the neonatal period, with heterozygous family members being unaffected.Methods: All OI-associated genes were sequenced. Primary human osteoblast-like cell (hOB) and fibroblast (FB) cultures were obtained for qPCR, and steady-state collagen biochemistry. FB, hOB and skin biopsies were ultrastructurally analyzed. Bone was analyzed by |mu CT, histomorphometry, quantitative backscattered electron imaging (qBEI), and Raman microspectroscopy.Results: The proband, a boy with severe OI, had blue sclera and tooth agenesis A homozygous CREB3L1 stop codon mutation was detected by sequencing, while several family members were heterozygotes Markedly low levels of CREB3L1 mRNA were confirmed by qPCR in hOBs (16%) and FB (21%), however, collagen I levels were only reduced in hOBs (5-10%) Electron microscopy of hOBs showed pronounced alterations, with numerous myelin figures and diminished RER vs. normal ultrastructure of FB. Bone histomorphometry and qBEI were similar to collagen I OI, with low trabecular thickness and mineral apposition rate, and increased bone matrix mineralization. Raman microspectroscopy revealed low level of glycosaminoglycans. Clinical response to lifelong bisphosphonate treatment was as expected in severe OI with steadily increasing bone mineral density, but despite this the boy suffered repeated childhood fractures.Conclusions: Deficiency of OASIS can cause severe OI compatible with surviving the neonatal period A marked decrease of collagen type I transcription was noted in bone tissue, but not in skin, and ultrastructure of hOBs was pathological. Results also suggested OASIS involvement in glycosaminoglycan secretion in bone.
  • Månsson, Viktor (författare)
  • Haemophilus influenzae – typing, epidemiology and beta-lactam resistance
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Haemophilus influenzae is a common cause of respiratory tract infections such as acute otitis media (AOM), exacerbations of chronic obstructive pulmonary disease (COPD) and pneumonia. The species is subdivided into encapsulated and non-encapsulated strains, designated type a-f and nontypeable H. influenzae (NTHi), respectively. Prior to introduction of polysaccharide-protein conjugate vaccines against H. influenzae type b (Hib) in childhood vaccination programmes this serotype frequently caused severe invasive infections in small children. Nowadays invasive disease by Hib is rare, but cases still occur. At present, NTHi is the dominating type to cause invasive disease and invasive NTHi disease appears to be increasing. Nontypeable H. influenzae disease severity traditionally has been considered largely host dependant. In parallel, non-beta-lactamase mediated beta-lactam resistance among NTHi is also increasing. In the first two studies of this thesis, we investigated capsule typing of H. influenzae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), a technology routinely used for bacterial species identification. Mass spectra of the different types of encapsulated H. influenzae were highly similar within each type and separable from each other. The differences in mass spectra relied on the clonal population structure of encapsulated H. influenzae, with conserved type specific genetic lineages. Mass spectra of NTHi were diverse, due to their genetic heterogeneity. Following construction of a comprehensive reference database, MALDI-TOF MS showed high accuracy for capsule typing of H. influenzae. In the third study of the thesis, a clonal group of NTHi with resistance against beta-lactam antibiotics was investigated. The clonal group accounted for one quarter of clinical respiratory H. influenzae isolates with non-beta-lactamase mediated beta-lactam resistance in the study region. Furthermore, patients infected by isolates of the clonal group had an increased risk of hospitalization compared to patients infected by other NTHi, indicating enhanced virulence traits. The clonal group was also found among invasive isolates. In the final study of the thesis we retrospectively compared benzylpenicillin, whose effect on H. influenzae is debated, to wide spectrum beta-lactams (WSBLs) as empirical treatment of H. influenzae lower respiratory tract infections in patients requiring hospitalization. Empirical treatment with benzylpenicllin was not associated with higher mortality or increased risk of hospital readmission compared to treatment with WSBLs. The early clinical response rate was, however, lower for patients receiving benzylpenicillin, which was attributed mainly to a lower response rate in patients infected with beta-lactamase producing isolates. In conclusion this thesis shows that MALDI-TOF MS can be efficiently used for rapid capsule typing of H. influenzae. The newly developed method can be valuable for typing of invasive H. influenzae isolates and for surveillance of Hib vaccination efficacy. The studied clonal group appears to harbour enhanced virulence traits. This indicates that bacterial factors may affect NTHi disease severity more than previously considered, and possibly contribute to the increased incidence of invasive NTHi disease. Finally, although the effect of benzylpenicillin on H. influenzae is debated, empirical treatment of lower respiratory tract infections of mild to moderate severity caused by H. influenzae with the agent appears safe
  • Paslawski, Wojciech, et al. (författare)
  • alpha-synuclein-lipoprotein interactions and elevated ApoE level in cerebrospinal fluid from Parkinson's disease patients
  • 2019
  • Ingår i: ; 116:30, s. 15226-15235
  • Tidskriftsartikel (refereegranskat)abstract
    • The progressive accumulation, aggregation, and spread of alpha-synuclein (alpha SN) are common hallmarks of Parkinson's disease (PD) pathology. Moreover, numerous proteins interact with alpha SN species, influencing its toxicity in the brain. In the present study, we extended analyses of alpha SN-interacting proteins to cerebrospinal fluid (CSF). Using coimmunoprecipitation, followed by mass spectrometry, we found that alpha SN colocalize with apolipoproteins on lipoprotein vesicles. We confirmed these interactions using several methods, including the enrichment of lipoproteins with a recombinant alpha SN, and the subsequent uptake of prepared vesicles by human dopaminergic neuronal-like cells. Further, we report an increased level of ApoE in CSF from early PD patients compared with matched controls in 3 independent cohorts. Moreover, in contrast to controls, we observed the presence of ApoE-positive neuromelanin-containing dopaminergic neurons in substantia nigra of PD patients. In conclusion, the cooccurrence of alpha SN on lipoprotein vesicles, and their uptake by dopaminergic neurons along with an increase of ApoE in early PD, proposes a mechanism(s) for alpha SN spreading in the extracellular milieu of PD.
  • Peura, Sari, et al. (författare)
  • Normal values for calprotectin in stool samples of infants from the population-based longitudinal born into life study
  • 2018
  • Ingår i: ; 78:1-2, s. 120-124
  • Tidskriftsartikel (refereegranskat)abstract
    • Faecal calprotectin is a protein used as a diagnostic marker for inflammatory bowel diseases. We determined upper limits for normal calprotectin values for neonatal, 6, 12 and 24 months old children using a turbidimetric immunoassay in a cohort of Swedish children. The advantage of the method is that opposite to previously used enzyme-linked immunosorbent assay (ELISA) method, it enables measuring single samples, and thus, shortens the analysis time significantly. There were 72 samples (41.7% female) collected neonatally, 63 samples (34.9% female) at 6 months, 60 samples (40.0% female) at 12 months and 51 samples (43.1% female) at 24 months. The upper limits for normal values were 233, 615, 136 and 57 µg mg-1 for infants aged 0, 6, 12 and 24 months, respectively.
  • Pilebro, Björn, et al. (författare)
  • Positron emission tomography (PET) utilizing Pittsburgh compound B (PIB) for detection of amyloid heart deposits in hereditary transthyretin amyloidosis (ATTR)
  • 2018
  • Ingår i: ; 25:1, s. 240-248
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: DPD scintigraphy has been advocated for imaging cardiac amyloid in ATTR amyloidosis. PET utilizing (11)C-Pittsburgh compound B (PIB) is the gold standard for imaging brain amyloid in Alzheimer's disease. PIB was recently shown to identify cardiac amyloidosis in both AL and ATTR amyloidosis. In the ATTR population, two types of amyloid fibrils exist, one containing fragmented and full-length TTR (type A) and the other only full-length TTR (type B). The aim of this study was to further evaluate PIB-PET in patients with hereditary ATTR amyloidosis.METHODS: Ten patients with biopsy-proven V30M ATTR amyloidosis and discrete or no signs of cardiac involvement were included. Patients were grouped according to TTR-fragmentation. All underwent DPD scintigraphy, echocardiography, and PIB-PET. A left ventricular PIB-retention index (PIB-RI) was established and compared to five normal volunteers.RESULTS: PIB-RI was increased in all patients (P < 0.001), but was significantly higher in type B than in type A (0.129 ± 0.041 vs 0.040 ± 0.006 min(-1), P = 0.009). Cardiac DPD uptake was elevated in group A and absent in group B.CONCLUSION: PIB-PET, in contrast to DPD scintigraphy, has the potential to specifically identify cardiac amyloid depositions irrespective of amyloid fibril composition. The heart appears to be a target organ for amyloid deposition in ATTR amyloidosis.
  • Pyykko, Okko T. (författare)
  • Incidence, Comorbidities, and Mortality in Idiopathic Normal Pressure Hydrocephalus
  • 2018
  • Ingår i: World Neurosurgery. - : ELSEVIER SCIENCE INC. - 1878-8750 .- 1878-8769. ; 112, s. E624-E631
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECT: To investigate the incidence, comorbidities, mortality, and causes of death in idiopathic normal pressure hydrocephalus (iNPH). METHODS: A cohort of 536 patients with possible NPH from a defined population with a median follow-up time of 5.1 years, (range 0.04-19.9 years) was included in the study. Patients were evaluated by brain imaging and intraventricular pressure monitoring, with a brain biopsy specimen immunostained against amyloid-beta and hyper-phosphorylated tau. Hospital records were reviewed for vascular diseases and type 2 diabetes mellitus (T2DM). Death certificates and yearly population of the catchment area were obtained from national registries. RESULTS: A total of 283 patients had a clinical diagnosis of iNPH, leading to a median annual incidence of 1.58 iNPH patients per 100,000 inhabitants (range, 0.8-4.5). Alzeimer disease-related brain biopsy findings were less frequent in iNPH patients than in non-iNPH patients (P < 0.05). An overrepresentation of hypertension (52% vs. 33%, P < 0.001) and T2DM (23% vs. 13%, P = 0.002) was noted in iNPH patients. Age (hazard ratio [HR] 1.04/year, 95% confidence interval [CI] 1.03-1.06, P< 0.001) and T2DM (HR 1.63, 95% CI 1.23-2.16, P < 0.001) increased the risk of death in the iNPH patients and in the total population. iNPH was associated with decreased risk of death (HR 0.63, 95% CI 0.50-0.78, P < 0.001). The most frequent causes of death were cardiovascular and cerebrovascular disease. Dementia as a cause of death was more common in non-iNPH patients (27% vs. 10%, P < 0.001). CONCLUSIONS: Hypertension and T2DM are common in iNPH and the latter causes excess mortality in the affected patients.
  • Rauramaa, Tuomas (författare)
  • Epilepsy in neuropathologically verified Alzheimer's disease
  • 2018
  • Ingår i: Seizure. - : W B SAUNDERS CO LTD. - 1059-1311 .- 1532-2688. ; 58, s. 9-12
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Subjects with Alzheimer's disease (AD) have been shown to be at a higher risk for epilepsy. The vast majority of the previous studies have not included a full neuropathological examination. Methods: The objective of this study was to assess the prevalence of epilepsy and clinicopathological characteristics in a well-defined study group of 64 subjects with AD. We evaluated the clinicopathological findings in 64 subjects (mean age at death 85 +/- 8.6 years) from a longitudi-nal study cohort of patients with dementia. Results: Eleven out of the 64 subjects (17%) had a history of epilepsy, which is comparable to previous studies. The subjects with AD and epilepsy were significantly younger at the time of AD diagnosis and at the time of hospitalisation. In addition, their duration of AD was longer. Concomitant neuropathology in addition to AD was common in both groups and the ApoE genotypes did not differ significantly between the groups. Conclusion: The strength of this study is a thorough neuropathological examination of all study subjects. Our findings support the previous literature regarding the prevalence of epilepsy in subjects with AD. We have shown that the subjects with AD and epilepsy differ significantly from the subjects without epilepsy.
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