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| 3. |
- Eneman, K., et al.
(author)
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Evaluation of signal enhancement algorithms for hearing instruments
- 2008
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Conference paper (peer-reviewed)abstract
- In the frame of the HearCom1 project five promising signal enhancement algorithms are validated for future use in hearing instrument devices. To assess the algorithm performance solely based on simulation experiments, a number of physical evaluation measures have been proposed that incorporate basic aspects of normal and impaired human hearing. Additionally, each of the algorithms has been implemented on a common real-time hardware/software platform, which facilitates a profound subjective validation of the algorithm performance. Recently, a multicenter study has been set up across five different test centers in Belgium, the Netherlands, Germany and Switzerland to perceptually evaluate the selected signal enhancement approaches with normally hearing and hearing impaired listeners.
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| 4. |
- Benson, Mikael, 1954, et al.
(author)
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Gene profiling reveals decreased expression of uteroglobin and other anti-inflammatory genes in nasal fluid cells from patients with intermittent allergic rhinitis
- 2005
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In: Clin Exp Allergy. - : Wiley. ; 35:4, s. 473-478
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Journal article (peer-reviewed)abstract
- BACKGROUND: Intermittent allergic rhinitis (IAR) results from interactions between a large number of pro- and anti-inflammatory mediators. Little is known about anti-inflammatory mediators in IAR. DNA microarrays allow simultaneous analysis of the whole transcriptome in a sample. OBJECTIVE: To identify anti-inflammatory transcripts in nasal fluid cells from patients with IAR during season and from healthy controls. METHODS: Nasal lavage fluids were obtained from 15 patients with symptomatic birch/and or grass pollen-induced IAR and 28 healthy controls. RNA was extracted from the nasal fluid cells and pooled into one patient- and one control pool. These were analysed with DNA microarrays containing more than 44,927 genes and variants. RESULTS: Seventeen thousand three hundred and fifty three genes were expressed in the controls and 17 928 in the patients. One thousand five hundred and seventy nine of the genes had higher expression in patients than in controls, and 1570 had lower expression in patients. Out of 189 up-regulated inflammatory genes, 187 were pro-inflammatory and two were anti-inflammatory. These genes regulated key steps of inflammation, ranging from influx of leukocytes to immunoglobulin production. By comparison, out of 49 down-regulated inflammatory genes, 36 were pro-inflammatory and 13 were anti-inflammatory. The anti-inflammatory gene that decreased most in expression in the patients was uteroglobin (also known as Clara Cell protein 16, CC16). The nasal fluid concentrations of uteroglobin protein were significantly lower in patients than in controls, 5.43+/-1.53 and 12.93+/-2.53 ng/mL, respectively (P<0.05). CONCLUSION: IAR is associated with decreased expression of uteroglobin and other anti-inflammatory genes.
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| 5. |
- Bergenfelz, A, et al.
(author)
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Pancreastatin plasma levels in patients with primary hyperparathyroidism
- 2000
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In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 24:12, s. 83-1579
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Journal article (peer-reviewed)abstract
- Pancreastatin, a C-terminally amidated peptide derived from chromogranin A, is known to inhibit insulin secretion, pancreatic enzyme release, and gastric acid secretion. It also inhibits parathyroid hormone (PTH) secretion in animals. The physiologic and clinical relevance of pancreastatin in humans, however, is not known. Because pancreastatin has been found in parathyroid adenomas, we investigated the plasma levels in patients with primary hyperparathyroidism (pHPT). Thirteen patients operated on for solitary parathyroid adenoma were investigated. Plasma levels of pancreastatin and serum levels of ionized calcium and intact PTH were measured before and 6 weeks after operation. In 10 patients the levels were also monitored before and 60 minutes after adenoma excision. The adenomas were investigated for pancreastatin immunoreactivity by immunocytochemistry. The median weight of the excised parathyroid adenoma was 0.64 g (range 0.07-2.00 g). Cells displaying pancreastatin immunoreactivity were present in all adenomas examined and varied in number and immunostaining intensity among and within the adenomas. Intraoperatively, after adenoma excision the levels of PTH and pancreastatin declined (p < 0.01), whereas the levels of ionized calcium did not change (p = 0.96). At the 6-week follow-up the levels of ionized calcium and PTH had decreased compared to the preoperative levels (p < 0.01), and all patients were normocalcemic. In contrast, the pancreastatin levels were not changed (14.5 +/- 6.1 pmol/L preoperatively vs. 12.8 +/- 11.2 pmol/L 6 weeks postoperatively; p = 0.12). In patients with pHPT, pancreastatin is likely to be produced by the parathyroid adenoma. The changes in pancreastatin levels immediately after surgery warrant further investigation.
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| 6. |
- Jönsson, Göran B, et al.
(author)
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Genomic subtypes of breast cancer identified by array-comparative genomic hybridization display distinct molecular and clinical characteristics
- 2010
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 12:3
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Journal article (peer-reviewed)abstract
- Introduction: Breast cancer is a profoundly heterogeneous disease with respect to biologic and clinical behavior. Gene-expression profiling has been used to dissect this complexity and to stratify tumors into intrinsic gene-expression subtypes, associated with distinct biology, patient outcome, and genomic alterations. Additionally, breast tumors occurring in individuals with germline BRCA1 or BRCA2 mutations typically fall into distinct subtypes. Methods: We applied global DNA copy number and gene-expression profiling in 359 breast tumors. All tumors were classified according to intrinsic gene-expression subtypes and included cases from genetically predisposed women. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was used to identify significant DNA copy-number aberrations and genomic subgroups of breast cancer. Results: We identified 31 genomic regions that were highly amplified in > 1% of the 359 breast tumors. Several amplicons were found to co-occur, the 8p12 and 11q13.3 regions being the most frequent combination besides amplicons on the same chromosomal arm. Unsupervised hierarchical clustering with 133 significant GISTIC regions revealed six genomic subtypes, termed 17q12, basal-complex, luminal-simple, luminal-complex, amplifier, and mixed subtypes. Four of them had striking similarity to intrinsic gene-expression subtypes and showed associations to conventional tumor biomarkers and clinical outcome. However, luminal A-classified tumors were distributed in two main genomic subtypes, luminal-simple and luminal-complex, the former group having a better prognosis, whereas the latter group included also luminal B and the majority of BRCA2-mutated tumors. The basal-complex subtype displayed extensive genomic homogeneity and harbored the majority of BRCA1-mutated tumors. The 17q12 subtype comprised mostly HER2-amplified and HER2-enriched subtype tumors and had the worst prognosis. The amplifier and mixed subtypes contained tumors from all gene-expression subtypes, the former being enriched for 8p12-amplified cases, whereas the mixed subtype included many tumors with predominantly DNA copy-number losses and poor prognosis. Conclusions: Global DNA copy-number analysis integrated with gene-expression data can be used to dissect the complexity of breast cancer. This revealed six genomic subtypes with different clinical behavior and a striking concordance to the intrinsic subtypes. These genomic subtypes may prove useful for understanding the mechanisms of tumor development and for prognostic and treatment prediction purposes.
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| 7. |
- Luts, Heleen, et al.
(author)
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Multicenter evaluation of signal enhancement algorithms for hearing aids
- 2010
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In: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966 .- 1520-8524. ; 127:3, s. 1491-1505
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Journal article (peer-reviewed)abstract
- In the framework of the European HearCom project, promising signal enhancement algorithms were developed and evaluated for future use in hearing instruments. To assess the algorithms' performance, five of the algorithms were selected and implemented on a common real-time hardware/software platform. Four test centers in Belgium, The Netherlands, Germany, and Switzerland perceptually evaluated the algorithms. Listening tests were performed with large numbers of normal-hearing and hearing-impaired subjects. Three perceptual measures were used: speech reception threshold (SRT), listening effort scaling, and preference rating. Tests were carried out in two types of rooms. Speech was presented in multitalker babble arriving from one or three loudspeakers. In a pseudo-diffuse noise scenario, only one algorithm, the spatially preprocessed speech-distortion-weighted multi-channel Wiener filtering, provided a SRT improvement relative to the unprocessed condition. Despite the general lack of improvement in SRT, some algorithms were preferred over the unprocessed condition at all tested signal-to-noise ratios (SNRs). These effects were found across different subject groups and test sites. The listening effort scores were less consistent over test sites. For the algorithms that did not affect speech intelligibility, a reduction in listening effort was observed at 0 dB SNR. (C) 2010 Acoustical Society of America. [DOI: 10.1121/1.3299168]
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| 8. |
- Luts, L, et al.
(author)
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Parathyroid function and histology in patients with parathyroid adenoma : correlation of clinical and morphologic findings
- 1997
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In: World Journal of Surgery. - 0364-2313. ; 21:5, s. 63-553
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Journal article (peer-reviewed)abstract
- Serum levels of parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium, creatinine, and vitamin D and the glomerular filtration rate were compared with the histologic properties and expression of PTH and chromogranin A in excised parathyroid adenomas from patients with primary hyperparathyroidism (pHPT). PTH and chromogranin A were detected immunohistochemically, and their mRNA was demonstrated by in situ hybridization with quantification of their mRNA levels by image analysis. There was a positive correlation between the cellular levels of PTH mRNA and the cellular levels of chromogranin A mRNA (r = 4.4; p < 0.05). However, within certain parts of the adenomas, mostly consisting of chief cells, the expression of PTH mRNA and chromogranin A mRNA was heterogeneous and the levels did not correspond to each other. A reduced suppressibility of PTH in patients with pHPT was confirmed. Although cellular levels of PTH and chromogranin A and their mRNAs were low in the oxyphilic parts of the adenomas, there was no correlation between the amount of oxyphilic cells in the adenomas and the suppressibility of PTH by calcium. There was also no association between the cellular levels of PTH mRNA or chromogranin A mRNA as studied by image analysis and "calcium sensitivity." Our results thus demonstrate that although PTH and chromogranin A mRNA levels are in general correlated to each other there are differences in their expression within and between individual parathyroid adenomas. It therefore seems likely that the expression of PTH and chromogranin A are differentially regulated, and that PTH and chromogranin A may not always be co-secreted. This point could be of importance, as chromogranin A and its cleavage products are known to influence PTH secretion.
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| 9. |
- Luts, L, et al.
(author)
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Peptide-containing nerve fibres in normal human parathyroid glands and in human parathyroid adenomas
- 1995
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In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 133:5, s. 51-543
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Journal article (peer-reviewed)abstract
- There are only a few studies on the innervation of the human parathyroid glands and the content of neurotransmitters. We therefore studied the occurrence and distribution of peptide-containing and adrenergic nerve fibres and the coexistence pattern of neuromessengers by immunocytochemistry in normal (unaffected) and adenomatous parathyroid glands from patients undergoing surgery for parathyroid adenoma. The unaffected parathyroid glands had a moderate-to-rich supply of nerve fibres and terminals containing two general neuronal markers, protein gene product 9.5 (PGP 9.5) and synaptophysin, neuropeptide Y (NPY) and tyrosine hydroxylase (TH). They were seen close to blood vessels and, occasionally, among the endocrine cells. Only a few nerves contained calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), substance P (SP) and pituitary adenylate cyclase-activating peptide (PACAP). The general density of innervation, using PGP 9.5 and synaptophysin as markers, varied greatly among the different adenomas examined. This applied also to the density of fibres and terminals containing specific types of messengers. Some of the tumours had a rich supply of TH- and NPY-containing nerve fibres, while others contained only few scattered fibres. The CGRP-containing fibres varied from moderate in number to no detectable fibres. The PACAP-, SP- and VIP-containing fibres were always very few or not detectable. It is not inconceivable that the wide variation in general density of the innervation and frequency of peptide-containing nerves among individual parathyroid adenomas is of significance for their hormone secretory behaviour.
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| 10. |
- Schmidt, D, et al.
(author)
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The effect of the vasoactive intestinal polypeptide agonist Ro 25-1553 on induced tone in isolated human airways and pulmonary artery
- 2001
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In: Naunyn-Schmiedeberg's Archives of Pharmacology. - : Springer Science and Business Media LLC. - 0028-1298 .- 1432-1912. ; 364:4, s. 314-320
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Journal article (peer-reviewed)abstract
- Ro 25-1553 is a metabolically stable analogue of endogenous vasoactive intestinal polypeptide (VIP). This compound is a potent bronchodilator in vitro as well as in vivo. Moreover, Ro 25-1553 has been shown to be highly selective of the VPAC2 receptor. We assessed the effect of Ro 25-1553 on isolated human bronchi and pulmonary arteries in vitro. Macroscopically normal human airways and pulmonary arteries were obtained from patients undergoing surgery for lung cancer. The relaxing capability of Ro 25-1553 on bronchial and pulmonary artery tone was measured using standard techniques. Bronchial rings were pre-contracted with 0.1 mM histamine, and tone in pulmonary artery rings was induced with 10 microM PGF2alpha. Increasing concentrations of Ro 25-1553 within a range of 1 pM to 10 microM were added and isometric tension changes were recorded. Ro 25-1553 caused a concentration-dependent relaxation of airway and pulmonary artery preparations, with an EC50 of approximately 10 nM and a maximal relaxation of 70%-75% of the induced tone. The presence of VPAC2 receptors in the two tissues, though low in density, was confirmed by in situ hybridization, immunocytochemistry and ligand binding. These findings indicate that the VIP analogue Ro 25-1553 may be useful in the treatment of asthma and/or chronic obstructive pulmonary diseases.
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| 11. |
- Staaf, Johan, et al.
(author)
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Identification of Subtypes in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Reveals a Gene Signature Prognostic of Outcome.
- 2010
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In: Journal of Clinical Oncology. - 1527-7755. ; 28:11, s. 1813-1820
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Journal article (peer-reviewed)abstract
- PURPOSE: Human epidermal growth factor receptor 2 (HER2) gene amplification or protein overexpression (HER2 positivity) defines a clinically challenging subgroup of patients with breast cancer (BC) with variable prognosis and response to therapy. We aimed to investigate the heterogeneous biologic appearance and clinical behavior of HER2-positive tumors using molecular profiling. PATIENTS AND METHODS: Hierarchical clustering of gene expression data from 58 HER2-amplified tumors of various stage, histologic grade, and estrogen receptor (ER) status was used to construct a HER2-derived prognostic predictor that was further evaluated in several large independent BC data sets. RESULTS: Unsupervised analysis identified three subtypes of HER2-positive tumors with mixed stage, histologic grade, and ER status. One subtype had a significantly worse clinical outcome. A prognostic predictor was created based on differentially expressed genes between the subtype with worse outcome and the other subtypes. The predictor was able to define patient groups with better and worse outcome in HER2-positive BC across multiple independent BC data sets and identify a sizable HER2-positive group with long disease-free survival and low mortality. Significant correlation to prognosis was also observed in basal-like, ER-negative, lymph node-positive, and high-grade tumors, irrespective of HER2 status. The predictor included genes associated with immune response, tumor invasion, and metastasis. CONCLUSION: The HER2-derived prognostic predictor provides further insight into the heterogeneous biology of HER2-positive tumors and may become useful for improved selection of patients who need additional treatment with new drugs targeting the HER2 pathway.
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| 12. |
- Van den Bosch, T., et al.
(author)
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Detection of intracavitary uterine pathology using offline analysis of three-dimensional ultrasound volumes: interobserver agreement and diagnostic accuracy
- 2012
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In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 40:4, s. 459-463
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Journal article (peer-reviewed)abstract
- Objective To estimate the diagnostic accuracy and interobserver agreement in predicting intracavitary uterine pathology at offline analysis of three-dimensional (3D) ultrasound volumes of the uterus. Methods 3D volumes (unenhanced ultrasound and gel infusion sonography with and without power Doppler, i.e. four volumes per patient) of 75 women presenting with abnormal uterine bleeding at a bleeding clinic were assessed offline by six examiners. The sonologists were asked to provide a tentative diagnosis. A histological diagnosis was obtained by hysteroscopy with biopsy or operative hysteroscopy. Proliferative, secretory or atrophic endometrium was classified as normal histology; endometrial polyps, intracavitary myomas, endometrial hyperplasia and endometrial cancer were classified as abnormal histology. The diagnostic accuracy of the six sonologists with regard to normal/abnormal histology and interobserver agreement were estimated. Results Intracavitary pathology was diagnosed at histology in 39% of patients. Agreement between the ultrasound diagnosis and the histological diagnosis (normal vs abnormal) ranged from 67 to 83% for the six sonologists. In 45% of cases all six examiners agreed with regard to the presence/absence of intracavitary pathology. The percentage agreement between any two examiners ranged from 65 to 91% (Cohen's ?, 0.310.81). The Schouten ? for all six examiners was 0.51 (95% CI, 0.400.62), while the highest Schouten ? for any three examiners was 0.69. Conclusion When analyzing stored 3D ultrasound volumes, agreement between sonologists with regard to classifying the endometrium/uterine cavity as normal or abnormal as well as the diagnostic accuracy varied substantially. Possible actions to improve interobserver agreement and diagnostic accuracy include optimization of image quality and the use of a consistent technique for analyzing the 3D volumes. Copyright (c) 2012 ISUOG. Published by John Wiley & Sons, Ltd.
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| 13. |
- Van den Bosch, T., et al.
(author)
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Effect of gel-instillation sonography on Doppler ultrasound findings in endometrial polyps
- 2011
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In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 38:3, s. 355-359
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Journal article (peer-reviewed)abstract
- Objective Saline infusion sonohysterography has been reported to suppress the color signal within the endometrium at color or power Doppler evaluation. The aim of this study was to evaluate if gel-instillation sonography (GIS) affects the power Doppler signal in patients with endometrial polyps. Methods Ultrasound volumes of the uterus, obtained by three-dimensional ultrasound imaging of 25 women with histologically confirmed endometrial polyps, were assessed offline by six gynecologists with a special interest in gynecological ultrasound. Each woman contributed four volumes: one gray-scale volume and one power Doppler volume before GIS, and one gray-scale volume and one power Doppler volume at GIS. Power Doppler features before and after gel infusion were compared. Results At unenhanced ultrasound a pedicle artery was seen in 27-46% of cases, whereas, after gel infusion the examiners reported a pedicle artery in 30-46% of cases (Exact McNemar's test P-values ranged from 0.50 to 1.00). The level of agreement between unenhanced ultrasound and GIS ranged from 59 to 91% (Cohen's kappa values ranged from 0.17 to 0.79). There was no tendency for a pedicle artery to be identified less often at GIS than before gel instillation. Conclusion Gel infusion does not affect the power Doppler signal in patients with endometrial polyps. Copyright. (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.
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