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- Jungebluth, Philipp, et al.
(författare)
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Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite : a proof-of-concept study
- 2011
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 378:9808, s. 1997-2004
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Tidskriftsartikel (refereegranskat)abstract
- Background Tracheal tumours can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. We report the clinical transplantation of the tracheobronchial airway with a stem-cell-seeded bioartificial nanocomposite. Methods A 36-year-old male patient, previously treated with debulking surgery and radiation therapy, presented with recurrent primary cancer of the distal trachea and main bronchi. After complete tumour resection, the airway was replaced with a tailored bioartificial nanocomposite previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 h. Postoperative granulocyte colony-stimulating factor filgrastim (10 mu g/kg) and epoetin beta (40 000 UI) were given over 14 days. We undertook flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, multiplex, miRNA, and gene expression analyses. Findings We noted an extracellular matrix-like coating and proliferating cells including a CD105+ subpopulation in the scaffold after the reseeding and bioreactor process. There were no major complications, and the patient was asymptomatic and tumour free 5 months after trans plantation. The bioartificial nanocomposite has patent anastomoses, lined with a vascularised neomucosa, and was partly covered by nearly healthy epithelium. Post-operatively, we detected a mobilisation of peripheral cells displaying increased mesenchymal stromal cell phenotype, and upregulation of epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers. These findings, together with increased levels of regenerative-associated plasma factors, strongly suggest stem-cell homing and cell-mediated wound repair, extracellular matrix remodelling, and neovascularisation of the graft. Interpretation Tailor-made bioartificial scaffolds can be used to replace complex airway defects. The bioreactor reseeding process and pharmacological-induced site-specific and graft-specific regeneration and tissue protection are key factors for successful clinical outcome.
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- Lonn, Stefan, et al.
(författare)
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Mobile phone use and risk of parotid gland tumor
- 2006
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 164:7, s. 637-643
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Tidskriftsartikel (refereegranskat)abstract
- Handheld mobile phones were introduced in Denmark and Sweden during the late 1980s. This makes the Danish and Swedish populations suitable for a study aimed at testing the hypothesis that long-term mobile phone use increases the risk of parotid gland tumors. In this population-based case-control study, the authors identified all cases aged 20-69 years diagnosed with parotid gland tumor during 2000-2002 in Denmark and certain parts of Sweden. Controls were randomly selected from the study population base. Detailed information about mobile phone use was collected from 60 cases of malignant parotid gland tumors (85% response rate), 112 benign pleomorphic adenomas (88% response rate), and 681 controls (70% response rate). For regular mobile phone use, regardless of duration, the risk estimates for malignant and benign tumors were 0.7 (95% confidence interval: 0.4, 1.3) and 0.9 (95% confidence interval: 0.5, 1.5), respectively. Similar results were found for more than 10 years' duration of mobile phone use. The risk estimate did not increase, regardless of type of phone and amount of use. The authors conclude that the data do not support the hypothesis that mobile phone use is related to an increased risk of parotid gland tumors.
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- Henriksson, Gert
(författare)
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Clinical, immunological and olfactory aspects of sinusitis and nasal polyposis : with special reference to patients with cystic fibrosis
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The otorhinolaryngological approach to the problem concerning rhinosinusitis and nasal polyposis in the recessive genetic disorder of cystic fibrosis (CF) has been developed based on data from international studies. Opinions differ on how to treat the otolaryngological manifestations of CF (sinusitis, nasal polyps and hyposmia). This is the main reason why we decided to explore these questions in Sweden, in an attempt to find reasonable grounds for a logical way of treating these disorders in patients with CF. The immunological impact that the normal microflora could excert in the upper respiratory tract have until recently been unknown. In parallel studies of mouth and pharynx mucosa, indigenous flora (alpha-streptococcus) have been used to inhibit pathological species involved in e.g. tonsillitis and otitis. Aims: The aims of the work presented in this thesis were: 1. To determine the frequency of sinusitis and nasal polyps within the paediatric population and relate this to bacteriology, in-patient treatment and correlation with possible parallel risk factors as cystic fibrosis. 2. To compare the bacterial and inflammation status within the population of patients with CF (both children and adults) and to compare the frequency of nasal polyps and hyposmia/anosmia with the frequency of these findings present in the healthy population, highlighting how these affect the quality of life and the general health status in CF. 3. To study how the normal bacterial flora in the upper airways affects nasal inflammation in the case of a monoinfection. Methods: I. We have retrospectively analysed 13 years of data from an in-patient paediatric population for the frequency of sinusitis and nasal polyps. We have also examined bacteriology, treatment and risk factors. II & IV. We also studied the population of CF patients at their annual check-ups at the CF Centre of Karolinska University Hospital, Huddinge. A clinical endoscopical examination was carried out to determine the frequency of nasal polyps. The otolaryngological status was compared to the overall CF health status at the time of the examination. We carried out two studies of these patients: In the first study, a nasal lavage was carried out, revealing inflammation data of the upper airways (113 patients). In the second study, two different smell tests were carried out (122 patients). III. Germ-free rats were monoinfected with Mycoplasma pulmonis for 3 weeks (control animals were kept free of infection). The T-cell population of the mucosa of the nasal cavity were compared with or without infection to determine the difference in immunological response depending on the normal nasal flora. Results: I. Few of the in-patient paediatric patients with acute and chronic sinusitis needed surgical intervention. The risk factors, which include allergy, cilia dyskinesia and CF, were rare. Half of the paediatric population who underwent surgery for nasal polyps had CF. II & IV. The frequency of patients with nasal polyps in the CF population was 37-39%. The sense of smell of these patients was lower than in a healthy population when assessed by the butanol test and the identification tests. The prevalence of inflammation parameters such as IL-8 and lysozyme were elevated in nasal lavages. Other aspects of the overall health situation were not affected by the presence of nasal polyps or impairment in their sense of smell. III. The normal microbiota of the nasal cavity in rats modified the immunological response to the Mycoplasma pulmonis infection. TCRalphabeta+CD4+ Tcells were elevated both in the intraepithelial lining and in the lamina propria after three weeks of infection in GF rats. Conclusions: I. In-patients with paediatric sinusitis required few surgical interventions within a 13-year period at our clinic. Risk factors for sinusitis were rare: one risk factor was CF. Half of the paediatric population that underwent surgery for nasal polyps were diagnosed with CF. II. Patients with CF had elevated levels of IL-8 and of lysozyme in nasal lavage. The frequency of nasal polyps was 39%, as determined by endoscopy. Patients with nasal polyps displayed an elevated risk of chronic colonisation of Pseudomonas aeruginosa in the lower airways, but their overall health situation was not otherwise impaired. IV. The frequency of hyposmia and anosmia, as determined by a newly launched paediatric smell test in combination with other well-known olfaction tests (butanol and SOIT), was increased in a CF-population of 122 patients (aged 5-65 years). The subjective evaluation of the sense of smell differed markedly from the objective tests. No health parameters were correlated with the sense of smell in patients with CF. III. The normal microbiota of the nasal cavity modulated the mucosal T-cell response to a monoinfection with Mycoplasma pulmonis. An increased knowledge of the immunological influence of the normal microflora is important for developing strategies to inhibit pathological colonisation in the upper and lower airways in chronic diseases such as CF.
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- Seidl, Rainer, et al.
(författare)
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Deficient brain snRNP70K in patients with Down syndrome
- 2001
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Ingår i: Electrophoresis. - : Wiley-VCH Verlagsgesellschaft. - 0173-0835 .- 1522-2683. ; 22:1, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- The small nuclear ribonucleoprotein 70K (snRNP 70K; U1-70 kDa) is an integral part of the spliceosome, a large RNA-protein complex catalyzing the removal of introns from nuclear pre-mRNA. snRNP is one of the best-studied essential subunits of snRNPs, is highly conserved and its inactivation was shown to result in complete inhibition of splicing. Applying subtractive hybridization, we found a sequence with 100% identity to snRNP absent in fetal Down syndrome (DS) brain. This observation made us determine snRNP-mRNA steady-state levels and protein levels in brains of adult patients with DS. snRNP-mRNA and protein levels of five individual brain regions of DS and controls each, were determined by blotting techniques. snRNP-mRNA steady state levels were significantly decreased in DS brain. Performing Western blots with monoclonal and human antibodies, snRNP protein levels were decreased in several regions of DS brain, although one monoclonal antibody did not reveal different snRNP-immunoreactivity. Although decreased snRNP-protein could be explained by decreased mRNA-steady state levels, another underlying mechanism might be suggested: snRNP is one of the death substrates rapidly cleaved during apoptosis by interleukin-1-beta-converting enzyme-like (ICE) proteases, which was well-documented by several groups. As apoptosis is unrequivocally taking place in DS brain leading to permanent cell loses, decreased snRNP-protein levels may therefore reflect decreased synthesis and increased apoptosis-related proteolytic cleavage.
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