Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 42
Filter
2.
Exp Clin Endocrinol Diabetes ; 124(9): 529-534, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27437919

ABSTRACT

Limited data are available about the role of the serotonin 2B (5-HT2B) receptor in the function of human islets. This study aimed to test whether the 5-HT2B receptor contributes to glucose, insulin, and glucagon homeostasis in humans, utilizing a hereditary loss-of-function gene mutation in the receptor, which causes a 50% reduction in the production of the receptor protein in heterozygotes. This clinical study enrolled participants recruited by newspaper advertisements and from mental status examinations. A cohort of participants from a young Finnish founder population composed of 68 non-diabetic males with a mean age of 30 was divided into groups for comparison based on being a 5-HT2B receptor loss-of-function gene mutation (HTR2B Q20*) heterozygote carrier (n=11) or not (n=57). Serum levels of glucose, insulin, and glucagon were measured in a 5 h oral glucose tolerance test using a 75 g glucose challenge. Insulin resistance, insulin sensitivity, and beta cell activity were calculated using the homeostasis model assessment (HOMA2) and whole body insulin sensitivity index (WBISI), as well as the ratio of glucagon to insulin was noted. The areas under the curves (AUCs) were also determined. Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in cerebrospinal fluid (CSF). Covariate adjusted mean score comparisons were applied. Lower glucagon secretion and decreased glucose excursion were observed among HTR2B Q20* carriers as compared with individuals who were homozygotes for the wild-type Q20 allele (controls). No differences in insulin secretion, beta cell activity, insulin resistance, or insulin sensitivity were observed. The glucagon to insulin ratio differed between the HTR2B Q20* carriers and controls. CSF levels of 5-HIAA were similar between groups. Our findings indicate that the 5-HT2B receptor may contribute to the regulation of human glucagon and glucose homeostasis and the interplay between glucagon and insulin secretion.


Subject(s)
Blood Glucose/metabolism , Glucagon/blood , Insulin Resistance/genetics , Insulin/blood , Receptor, Serotonin, 5-HT2B/genetics , Adult , Cohort Studies , Finland , Glucose Tolerance Test , Humans , Male
3.
Lab Chip ; 15(4): 1213, 2015 Feb 21.
Article in English | MEDLINE | ID: mdl-25619960

ABSTRACT

Correction for 'Programmable microfluidic synthesis of spectrally encoded microspheres' by R. E. Gerver et al., Lab Chip, 2012, 12, 4716-4723.

4.
Lab Chip ; 12(22): 4716-23, 2012 Nov 21.
Article in English | MEDLINE | ID: mdl-23042484

ABSTRACT

Spectrally encoded fluorescent beads are an attractive platform for assay miniaturization and multiplexing in the biological sciences. Here, we synthesize hydrophilic PEG-acrylate polymer beads encoded with lanthanide nanophosphors using a fully automated microfluidic synthesis device. These beads are encoded by including varying amounts of two lanthanide nanophosphors relative to a third reference nanophosphor to generate 24 distinct ratios. These codes differ by less than 3% from their target values and can be distinguished from each other with an error rate of <0.1%. The encoded bead synthesis strategy we have used is readily extensible to larger numbers of codes, potentially up to millions, providing a new platform technology for assay multiplexing.


Subject(s)
Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Microfluidic Analytical Techniques/instrumentation , Microspheres , Nanostructures/chemistry , Nanotechnology/instrumentation , Acrylic Resins/chemistry , Chemistry Techniques, Synthetic , Feasibility Studies , Hydrophobic and Hydrophilic Interactions , Lanthanoid Series Elements/chemistry , Polyethylene Glycols/chemistry
5.
Lab Chip ; 12(21): 4287-95, 2012 Nov 07.
Article in English | MEDLINE | ID: mdl-22930180

ABSTRACT

Multilayer soft lithography (MSL) provides a convenient and low-cost method for fabricating poly(dimethyl siloxane) (PDMS) microfluidic devices with on-chip valves for automated and precise control of fluid flow. MSL casting molds for flow channels typically incorporate small patches of rounded positive photoresist at valve locations to achieve the rounded cross-sectional profile required for these valves to function properly. Despite the importance of these rounded features for device performance, a comprehensive characterization of how the rounding process affects feature dimensions and closing pressures has been lacking. Here, we measure valve dimensions both before and after rounding and closing pressures for 120 different valve widths and lengths at post-rounding heights between 15 and 84 µm, for a total of 1200 different geometries spanning a wide range of useful sizes. We find that valve height and width after rounding depend strongly on valve aspect ratios, with these effects becoming more pronounced for taller and narrower features. Based on the measured data, we provide a simple fitted model and an online tool for estimating the pre-rounding dimensions needed to achieve desired post-rounding dimensions. We also find that valve closing pressures are well explained by modelling valve membranes in a manner analogous to a suspension bridge, shedding new light on device physics and providing a practical model for estimating closing pressures during device design.


Subject(s)
Microfluidic Analytical Techniques , Dimethylpolysiloxanes/chemistry , Photochemical Processes , Pressure
6.
Acta Neurol Scand ; 126(5): 324-8, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22324518

ABSTRACT

OBJECTIVES: Endoscopic transthoracic sympathectomy (ETS) is a surgical procedure used to improve Quality of Life (QoL) in patients with treatment resistant palmar hyperhidrosis (PHH). The aim of this study was to test the hypothesis that low preoperative scores on The Everyday Life Questionnaire (EDLQ) would predict QoL improvement after surgery. MATERIALS AND METHODS: Pre- and post-operative QoL scores from a series of 30 consecutive patients who underwent ETS at our institution were analyzed. RESULTS: Preoperative QoL scores was a significant predictor of post-operative improvement across all dimensions covered by the questionnaire. CONCLUSION: Preoperative low QoL can be used as a guide in selecting patients with most improved QoL after ETS.


Subject(s)
Hyperhidrosis/psychology , Hyperhidrosis/surgery , Patient Satisfaction/statistics & numerical data , Quality of Life , Adult , Female , Humans , Male , Sympathectomy , Thoracoscopy , Treatment Outcome
7.
Acta Psychiatr Scand ; 123(1): 4-11, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20961293

ABSTRACT

OBJECTIVE: To present the technique of deep brain stimulation (DBS) and to evaluate the studies conducted on DBS in the treatment of therapy-refractory major depressive disorder (MDD). METHOD: A review of the literature on DBS in the treatment of MDD was conducted. RESULTS: The results of DBS in MDD have been presented in 2 case reports and 3 studies of 47 patients operated upon in 5 different target areas. Positive effects have been presented in all studies and side effects have been minor. DBS in the nucleus accumbens resulted in a mean reduction of Hamilton depression rating scale (HDRS) of 36% after 1 year and 30% of the 10 patients achieved remission. DBS in the internal capsule/ventral striatum resulted in a reduction of 44% after 1 year, and at the last evaluation after in mean 2 years, 40% of the 15 patients were in remission. The 20 patients with subcallosal cingulated gyrus DBS had a reduction of HDRS of 52% after 1 year, and 35% were within 1 point from remission or in remission. CONCLUSION: DBS is a promising treatment for therapy-refractory MDD. The published experience is, however, limited, and the method is at present an experimental therapy.


Subject(s)
Deep Brain Stimulation , Depressive Disorder, Major/therapy , Comparative Effectiveness Research , Deep Brain Stimulation/adverse effects , Deep Brain Stimulation/methods , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/physiopathology , Humans , Internal Capsule/physiopathology , Patient Care Team , Psychiatric Status Rating Scales , Risk Adjustment , Therapies, Investigational/adverse effects , Therapies, Investigational/methods , Treatment Outcome
8.
Eur J Cancer ; 42(3): 381-7, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16386891

ABSTRACT

Chromosomes 11q and 1p are commonly deleted in advanced-stage neuroblastomas and are therefore assumed to contain tumour suppressor genes involved in the development of this cancer. The two UFD2 yeast gene human homologues, UBE4A and UBE4B, involved in the ubiquitin/proteasome pathway, are located in 11q and 1p, respectively. UBE4B has previously been analysed for mutations and one mutation in the splice donor site of exon 9, c.1439 + 1G > C, was found in a neuroblastoma tumour with fatal outcome. We speculated that the homologue UBE4A might be involved in an alternative tumourigenesis pathway. The coding exons of UBE4A were therefore sequenced. One putative missense mutation (1028T > C, leading to I343T, residing in exon 8) was found in neuroblastoma tumour 20R8; this finding was confirmed by sequencing in both directions. The change, isoleucine (non-polar) to threonine (polar), was situated in a highly conserved amino acid region. In addition, two novel variants were also found in intronic sequences of UBE4A. It might be speculated that the proteins generated from UBE4B and UBE4A are involved in protecting the cell from environmental stress and that inactivation of either of them could contribute to malignancy.


Subject(s)
Chromosome Deletion , Nervous System Neoplasms/genetics , Neuroblastoma/genetics , Tumor Suppressor Proteins/genetics , Ubiquitin-Protein Ligases/genetics , Amino Acid Sequence , Chromosomes, Human, Pair 1/genetics , Chromosomes, Human, Pair 11/genetics , Humans , Mutation, Missense/genetics , Neural Crest , Nucleic Acid Amplification Techniques/methods , Polymerase Chain Reaction/methods , Polymorphism, Genetic/genetics , Sequence Alignment , Ubiquitin-Protein Ligase Complexes
9.
Br J Cancer ; 91(6): 1119-30, 2004 Sep 13.
Article in English | MEDLINE | ID: mdl-15328517

ABSTRACT

Neuroblastoma is characterised by a lack of TP53 mutations and no other tumour suppressor gene consistently inactivated has yet been identified in this childhood cancer form. Characterisation of a new gene, denoted APITD1, in the neuroblastoma tumour suppressor candidate region in chromosome 1p36.22 reveals that APITD1 contains a predicted TFIID-31 domain, representing the TATA box-binding protein-associated factor, TAF(II)31, which is required for p53-mediated transcription activation. Two different transcripts of this gene were shown to be ubiquitously expressed, one of them with an elevated expression in foetal tissues. Primary neuroblastoma tumours of all different stages showed either very weak or no measurable APITD1 expression, contrary to the level of expression observed in neuroblastoma cell lines. A reduced pattern of expression was also observed in a set of various tumour types. APITD1 was functionally tested by adding APITD1 mRNA to neuroblastoma cells, leading to the cell growth to be reduced up to 90% compared to control cells, suggesting APITD1 to have a role in a cell death pathway. Furthermore, we determined the genomic organisation of APITD1. Automated genomic DNA sequencing of the coding region of the gene as well as the promoter sequence in 44 neuroblastoma tumours did not reveal any loss-of-function mutations, indicating that mutations in APITD1 is not a common abnormality of neuroblastoma tumours. We suggest that low expression of this gene might interfere with the ability for apoptosis through the p53 pathway.


Subject(s)
Chromosomes, Human, Pair 1/genetics , Neuroblastoma/genetics , Tumor Suppressor Proteins/genetics , Amino Acid Sequence , Animals , Apoptosis Regulatory Proteins , Base Sequence , Chromosome Mapping , DNA Primers , Genes, Tumor Suppressor , Humans , Molecular Sequence Data , Mutation/genetics , Polymerase Chain Reaction , Promoter Regions, Genetic/genetics , RNA, Messenger/genetics , Sequence Alignment , Sequence Homology, Amino Acid , Tumor Suppressor Protein p53/genetics
11.
Br J Cancer ; 86(4): 596-604, 2002 Feb 12.
Article in English | MEDLINE | ID: mdl-11870543

ABSTRACT

The genes encoding Caspase-9 and DFF45 have both recently been mapped to chromosome region 1p36.2, that is a region alleged to involve one or several tumour suppressor genes in neuroblastoma tumours. This study presents an update contig of the 'Smallest Region of Overlap of deletions' in Scandinavian neuroblastoma tumours and suggests that DFF45 is localized in the region. The genomic organization of the human DFF45 gene, deduced by in-silico comparisons of DNA sequences, is described for the first time in this paper. In the present study 44 primary tumours were screened for mutation by analysis of the genomic sequences of the genes. In two out of the 44 tumours this detected in the DFFA gene one rare allele variant that caused a non-polar to a polar amino acid exchange in a preserved hydrophobic patch of DFF45. One case was hemizygous due to deletion of the more common allele of this polymorphism. Out of 194 normal control alleles only one was found to carry this variant allele, so in respect of it, no healthy control individual out of 97 was homozygous. Moreover, our RT-PCR expression studies showed that DFF45 is preferably expressed in low-stage neuroblastoma tumours and to a lesser degree in high-stage neuroblastomas. We conclude that although coding mutations of Caspase-9 and DFF45 are infrequent in neuroblastoma tumours, our discovery of a rare allele in two neuroblastoma cases should be taken to warrant further studies of the role of DFF45 in neuroblastoma genetics.


Subject(s)
Apoptosis/genetics , Caspases/genetics , Chromosomes, Human, Pair 1/genetics , Neoplasm Proteins/genetics , Neuroblastoma/genetics , Proteins/genetics , Alleles , Amino Acid Sequence , Apoptosis Regulatory Proteins , Base Sequence , Case-Control Studies , Caspase 9 , Caspases/metabolism , Cloning, Molecular , DNA Mutational Analysis , DNA Primers/chemistry , DNA, Neoplasm/analysis , Gene Frequency , Genes, Tumor Suppressor , Humans , Molecular Sequence Data , Mutation , Neoplasm Proteins/metabolism , Neuroblastoma/metabolism , Polymerase Chain Reaction , Proteins/metabolism
12.
Acta Paediatr ; 91(12): 1391-6, 2002.
Article in English | MEDLINE | ID: mdl-12578300

ABSTRACT

AIM: To study factors of relevance for the understanding of disclosure of child sexual abuse. METHODS: Cases from a Swedish district court involving 47 children in which allegations of child sexual abuse had been corroborated by a confession from the defendant were studied. RESULTS: Delayed disclosure was related to a close relationship with the perpetrator and young age at the first experience of abuse. Disrupted communication during the police interview was related to less violent abuse. CONCLUSION: The findings highlight the importance of social factors in children's disclosure of sexual abuse.


Subject(s)
Child Abuse, Sexual , Disclosure , Adolescent , Age Factors , Child , Child Abuse, Sexual/psychology , Female , Forensic Medicine , Humans , Interpersonal Relations , Male , Time Factors
14.
Lakartidningen ; 98(26-27): 3125-7, 2001 Jun 27.
Article in Swedish | MEDLINE | ID: mdl-11478206

ABSTRACT

A basic understanding of children's memories for emotional trauma is of importance for physicians and other health care professionals. The aim of this paper is to describe recent research and discuss important dilemmas within this field. The ability of infants and toddlers to verbally describe autobiographical memories is for several reasons limited. Very early experiences of e.g. intense pain can leave traces in the nervous system but of a kind which is not specific enough to allow retrospective conclusions about the nature of these experiences. Research during the past decades has relatively consistently demonstrated that pre-school children are more vulnerable to suggestion including abuse-related suggestions than are older children and adults. However, many children who have been subject to sexual abuse seem to maintain a lifelong silence about their experiences. The use of autobiographical testimony from young children is more complex and risky than many professionals believed about a decade ago. Establishing the knowledge derived from recent years' research in this area as a basis for clinical practice is one of the most important tasks for the future.


Subject(s)
Amnesia/psychology , Child Abuse, Sexual/psychology , Forensic Psychiatry , Memory , Stress, Psychological/psychology , Adult , Amnesia/etiology , Child , Child Behavior , Child, Preschool , Humans , Infant , Research , Stress, Psychological/complications , Suggestion , Verbal Behavior
15.
Med Pediatr Oncol ; 36(1): 61-6, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11464908

ABSTRACT

BACKGROUND: A common genetic feature of neuroblastomas, which is also an important prognostic factor, is deletion of chromosome region 1p. The deletion of 1p often involves a deletion of varying size, with a consensus region within the most distal bands 1p36.2-3. The neuroblastoma SRO (shortest region of overlap of (deletions) presented earlier by our group was defined distally by the cluster of loci D1S80/ D1Z2/CDC2L1 and proximally by loci D1S244, i.e., approximately 25 cM. The 1p deletions are, however, not restricted to neuroblastoma tumours. In fact, a large spectrum of tumour types display deletions to varying degrees of 1p. PROCEDURE: We have exploited the possibility of using deletions of other tumour types, preferentially that of germ cell tumours, and combining the deletions with that of the neuroblastoma SRO. Also in germ cell tumours, distal 1p-deletions have been shown to have prognostic significance. RESULTS: We found in our germ cell tumours a SRO ranging from D1S508 to D1S200. Interestingly, this region only partially overlapped (approximately 5 cm) with our neuroblastoma SRO in region D1S508 to D1S244. We have thus focused on analysing this smaller region in the search for genes involved in the genesis of different cancers. We have performed radiation hybrid mapping of a large number of markers, STSs, ESTs, and others known to reside in 1p. We have also initiated the development of a BAC contig of the region. FISH, and fibre-FISH mapping of BACs were also performed. CONCLUSIONS: The data presented here constitute an ongoing work with the aim of identifying and cloning gene(s) important for development of germ cell tumours, neuroblastomas, and possibly other tumours.


Subject(s)
Chromosomes, Human, Pair 1/genetics , Genes, Tumor Suppressor , Germinoma/genetics , Loss of Heterozygosity , Neuroblastoma/genetics , Chromosome Mapping , Chromosomes, Artificial, Bacterial , Chromosomes, Human, Pair 1/ultrastructure , Contig Mapping , Genetic Markers , Humans , In Situ Hybridization, Fluorescence , Lod Score , Polymerase Chain Reaction , Radiation Hybrid Mapping
17.
Cytogenet Cell Genet ; 89(1-2): 62-6, 2000.
Article in English | MEDLINE | ID: mdl-10894940

ABSTRACT

The processed product of the human gene preprocortistatin, the peptide cortistatin-17 (hCST-17), bears a strong structural resemblance to the peptide somatostatin (SST), which has an identical receptor binding domain. CST has affinity to all known SST receptor (SSTR) subtypes. Expression of both SST and its receptors has been shown in previous studies to have biological and clinical significance in neuroblastomas, with a putative role in tumor differentiation and apoptosis in vivo. In this work we have employed radiation hybrid mapping and BAC physical mapping to map the human preprocortistatin gene (CORT) to chromosome region 1p36.3-->p36.2, close to the genetic marker D1S244. D1S244 defines the centromeric border of the smallest region of overlap of deletion in our primary neuroblastoma material. We have also defined the genomic sequence of the gene by BAC sequencing and found that preprocortistatin consists of two exons divided by a 1-kb intron. Two polymorphic sites, neither of which causes amino acid exchange, have been detected in the coding region of the gene. Expression studies showed that preprocortistatin is expressed in neuroblastomas of all different stages, as well as in ganglioneuromas. Through genomic sequencing we made mutation analyses of exonic sequences in 49 primary neuroblastomas of all different stages, but no mutations could be detected.


Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 1/genetics , Consensus Sequence/genetics , Neuroblastoma/genetics , Neuropeptides/genetics , Protein Precursors/genetics , Base Sequence , Child , Contig Mapping , DNA Mutational Analysis , Exons/genetics , Humans , Hybrid Cells , In Situ Hybridization, Fluorescence , Introns/genetics , Lod Score , Loss of Heterozygosity/genetics , Molecular Sequence Data , Mutation/genetics , Neoplasm Staging , Neuroblastoma/pathology , Neuropeptides/physiology , Polymorphism, Genetic/genetics , RNA, Messenger/analysis , RNA, Messenger/genetics , Tumor Cells, Cultured
18.
Memory ; 8(2): 65-9, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10829123

ABSTRACT

Testimonies from 488 children given to the priests of the parish of Rättvik during a preliminary investigation of a Swedish witch panic in 1670-71 are examined in relation to records from parish catechetical meetings held in 1671. The result implies that children who knew and understood at least parts of Luther's catechism were less liable to have falsely alleged that they had been kidnapped by female satanists during the witch panic of the previous year. It is suggested that these effects were caused by differences in cognitive, social, and emotional resources among these children as compared to those who were unable to learn and understand any parts of Luther's catechism.


Subject(s)
Deception , Religion and Psychology , Witchcraft/history , Adolescent , Child , Educational Status , Female , History, 17th Century , Humans , Male , Personality Development , Sweden
19.
Int J Oncol ; 16(5): 943-9, 2000 May.
Article in English | MEDLINE | ID: mdl-10762630

ABSTRACT

Neuroblastoma is a childhood malignancy originating from cells of the sympathetic nervous system, exhibiting a marked diversity in outcome, with spontaneous regression at one end of the spectrum and severe disease and death at the other end. Features associated with frequent recurrence, a poor prognosis, and high tumor stage are loss of heterozygosity in the distal region of chromosome 1p and amplification of the N-myc gene. Patched 2 is a novel homologue to the tumor suppressor gene Patched 1, and has been mapped to 1p32-34, a part of chromosome 1 frequently deleted in high stage neuroblastoma tumors. RT-PCR analysis of 9 neuroblastoma cell lines showed expression of both Patched 1 and 2. We analyzed 14, mainly high stage, neuroblastoma tumors for mutations in the Patched 2 gene with denaturing HPLC using the Wave DNA fragment analysis system. In four tumor samples variations were detected within the coding sequence, and two of them gave rise to amino-acid substitutions. These variations were, however, also detected in normal DNA from the respective patients. We conclude that Patched 2 is expressed, but not frequently mutated, in high stage neuroblastomas and is therefore not likely to be involved in the genesis of this tumor.


Subject(s)
Chromosomes, Human, Pair 1 , Membrane Proteins/genetics , Neuroblastoma/genetics , Chromatography, High Pressure Liquid , Humans , Mutation , Neuroblastoma/pathology , Patched Receptors , Patched-1 Receptor , Patched-2 Receptor , Receptors, Cell Surface
20.
Int J Mol Med ; 3(6): 585-9, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10341287

ABSTRACT

In neuroblastoma, a childhood tumor of neural crest, a tumor suppressor gene located at 1p36 has been implicated to play a major role in tumor aggressiveness and clinical prognosis. We have examined 30 different staged primary neuroblastoma tumors using RT-PCR, for expression of the p73 gene located at 1p36.3, and its correlation to other clinical and biological features of these tumors. No correlation between expression of p73 and MYCN-amplification or 1p-deletion could be found, five of ten 1p-deleted tumors showed detectable levels of p73, and no mutations could be detected, neither in the retained alleles nor in any other parts of the material. In five 1p-deleted cases the origin of deletion were determined, two were of maternal and three of paternal origin. Both tumors with maternal 1p-loss showed detectable levels of p73, whereas the three with paternal loss did not. This suggests that p73 is expressed from the paternal allele only in advanced staged neuroblastoma tumors. Furthermore, it suggests absence of correlation between p73-expression and stage in these tumors. In conclusion, we could find no evidence for p73 being the neuroblastoma tumor suppressor gene in 1p36.


Subject(s)
DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Nervous System Neoplasms/metabolism , Neuroblastoma/metabolism , Nuclear Proteins/biosynthesis , Nuclear Proteins/genetics , Chromosomes, Human, Pair 1/genetics , Exons , Gene Amplification , Gene Expression , Genes, Tumor Suppressor/genetics , Genes, myc/genetics , Humans , In Situ Hybridization, Fluorescence , Mutation , Neoplasm Staging , Nervous System Neoplasms/genetics , Nervous System Neoplasms/pathology , Neuroblastoma/genetics , Neuroblastoma/pathology , Reverse Transcriptase Polymerase Chain Reaction , Sequence Deletion/genetics , Tumor Protein p73 , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Proteins
SELECTION OF CITATIONS
SEARCH DETAIL
...