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Biomedical subjects

L Andersson

Publications and source records attributed to L Andersson.

At least 109 records · Page 6Linked to original sources

Comparison of horse chromosome 3 with donkey and human chromosomes by cross-species painting and heterologous FISH mapping.

The melanocortin 1 receptor (MC1R), mast/stem cell growth factor receptor (KIT), and platelet-derived growth factor receptor alpha (PDGFRA) are loci that all belong to equine linkage group 2 (LG2). Of these, KIT was fluorescent in situ hybridization (FISH) mapped to ECA3q21 with equine cDNA and heterologous porcine BAC probes, while MC1R was localized to ECA3p12 and PDGFRA to ECA3q21 with heterologous porcine BAC probes. A three-step comparison between ECA3 and donkey chromosomes was carried out. First, microdissected ECA3 painting probe was used on donkey chromosomes, which showed disruption of the equine synteny. Next, human (HSA) Chromosomes (Chrs) 16q and 4 specific paints, known to be homologous to ECA3p and 3q, respectively, were applied to detect homologous chromosomal segment(s) in donkey. Finally, four genes (MC1R, ALB, PDGFRA, KIT) and two equine microsatellite markers (SGCV18 and SGCV33) located on ECA3 were FISH mapped to donkey chromosomes. The findings refined the cross species painting homology results and added six new markers to the nascent donkey gene map. The hypothesis that Tobiano coat color in horses may be associated with a chromosomal inversion involving genes within LG2 was tested by G-banding-based cytogenetic analysis and ordering of four loci-KIT, PDGFRA, albumin (ALB), and MC1R-in Tobiano and non-tobiano (homozygous as well as heterozygous) horses. However, no difference either in banding patterns or location/relative order of the genes was observed in the three classes. The study highlights successful FISH mapping of BAC probes across evolutionarily diverged species, viz., pig and horse/donkey, and represents the first use of large-sized individual clones across distantly related farm animals.

Animals↗

Close association between sequence polymorphism in the KIT gene and the roan coat color in horses.

The roan coat color in horses is controlled by a dominant allele that is lethal in the homozygous condition. Phenotypic similarities to some pigmentation disorders in human and mouse, combined with comparative mapping data, identified KIT, encoding the mast cell growth factor receptor, as a major candidate gene for the roan locus (Rn). Rn has previously been mapped to equine linkage group (LG) II. In this study, LGII was expanded with KIT and PDGFRA (platelet-derived growth factor receptor alpha) by use of RFLP and linkage analysis. Moreover, highly significant linkage disequilibrium between Rn and a KIT TaqI RFLP, representing a synonymous substitution in exon 19, was revealed. There was a strong KIT-Rn association in most breeds. Almost the complete KIT-encoding sequence was determined by sequence analysis of RT-PCR products. Comparison of horse KIT cDNA sequences, representing three different alleles (two different rn and one Rn), revealed five sequence polymorphisms and several mRNA splice variants, but none of these proved to be specifically associated with Rn. An insertion of a partial (79 bp) LINE1-element between exons 1 and 2, leading to a frameshift, represented about 30% of KIT transcripts in the Belgian roan horse used for the sequence analysis. However, an association between this L1 splice insertion and the roan phenotype was not verified when testing additional unrelated roan and non-roan horses from different breeds. The study strengthens the hypothesis that the roan coat color is controlled by KIT, but further analyses are needed to reveal the causative mutation(s).

Alternative Splicing↗

A radiation hybrid map of the RN region in pigs demonstrates conserved gene order compared with the human and mouse genomes.

We recently constructed a 7000-rad porcine whole-genome radiation hybrid (RH) panel with the primary objective of integrating linkage maps of microsatellites with evolutionary conserved genes into one ordered map. In order to evaluate the resolution of this RH panel, we have now constructed a radiation hybrid map of the Chromosome (Chr) 15q2.3-q2.6 region containing the RN gene. This gene has large effects on glycogen content in muscle and meat quality. Ten microsatellites covering a region of 55 centiMorgans and eight genes (AE3, FN1, IGFBP5, INHA, IRS1, PAX3, TNP1, and VIL1) were placed on the Sscr15 RH map. All the genes, except IRS1, were mapped on the RH map between microsatellites located in 15q2.5. The relative order of AE3 and INHA was inverted on the porcine physical map in comparison with the mouse linkage map. The order of other genes already mapped in the mouse (FN1, IGFBP5, TNP1, VIL1, INHA/AE3, and PAX3) was identical in pigs. We found no clear difference between the gene order on pig Chr 15 and human Chr 2q.

Animals↗

The Belt mutation in pigs is an allele at the Dominant white (I/KIT) locus.

A white belt is a common coat color phenotype in pigs and is determined by a dominant allele (Be). Here we present the result of a genome scan performed using a Hampshire (Belt)/Pietrain (non-Belt) backcross segregating for the white belt trait. We demonstrate that Belt maps to the centromeric region of pig Chromosome (Chr) 8 harboring the Dominant white (I/KIT) locus. Complete cosegregation between Belt and a single nucleotide polymorphism in the KIT gene was observed. Another potential candidate gene, the endothelin receptor type A gene (EDNRA), was excluded as it was assigned to a different region (SSC8q21) by FISH analysis. We argue that Belt is a regulatory KIT mutation on the basis of comparative data on mouse KIT mutants and our previous sequence analysis of the KIT coding sequence from a Hampshire pig. Quantitative PCR analysis revealed that Belt is not associated with a KIT duplication, as is the case for the Patch and Dominant white alleles. Thus, Belt is a fourth allele at the Dominant white locus, and we suggest that it is denoted I(Be).

Alleles↗

Treatment with paclitaxel 1-h infusion and carboplatin of patients with advanced non-small-cell lung cancer: a phase II multicentre trial. Joint Lung Cancer Study Group.

The primary aim of this phase II study was to determine the response rate of a combination of paclitaxel and carboplatin in advanced non-small cell lung cancer (NSCLC) in a multicentre setting. The secondary aim was to determine time to progression (TTP), 1-year survival rate and toxicity. 65 patients were treated and all of them were included in the follow up for survival and toxicity. 60 patients were followed for response rate and time to progression. 55% were stage IV patients and 45% stage IIIB patients. The treatment consisted of paclitaxel 200 mg/m2 given as a 1-h i.v. infusion and carboplatin given as a 30 min i.v. infusion and the latter was dosed by using the Calvert formula at an area under the concentration time curve (AUC) of 5. The glomerular filtration rate (GFR) was determined by iohexol clearance and was not calculated from the serum creatinine level. The chemotherapy courses were given every third week with a maximum number of six or eight courses for patients who responded late. As premedication we used 8 mg betamethasone 40 min prior to infusion and then 10 min later clemastin and cimetidine. One complete response and 18 partial responses were seen giving a response rate of 29%. 40% of the patients progressed during the treatment and 28% had stable disease. The median TTP was 22 weeks. At a minimum follow up of 1 year, the 1-year survival rate was 38% and the median survival rate was 41 weeks. Haematological toxicity was mild with no grade 4 leucopenia and only seven patients (11%) had grade 3 leucopenia. There was no grade 4 toxicity. Grade 3 toxicity was seen as myalgia 5%, allergic reaction 3% and peripheral neuropathy 6%. 15% of the patients had a dose reduction due to neurotoxicity. The haematological toxicity was much milder than we expected, probably because of more exact determination of the GFR. This trial confirms the results of earlier reported trials of the efficacy and the ease of the regimen as an out-patient treatment option in advanced NSCLC. The main problem with this treatment is peripheral neuropathy.

Adult↗

Periodontal and pulpal condition of the central incisors after midline osteotomy of the maxilla.

PURPOSE: The purpose of this study was to evaluate the periodontal and pulpal condition of the central incisors after Le Fort I and midline osteotomies for transverse expansion of the maxilla. PATIENTS AND METHODS: The series included 12 women and eight men, with an average age at operation of 28.4 years (range, 17 to 48 years). Each patient, examined retrospectively, underwent transverse expansion of the maxilla by combined Le Fort I and midline osteotomies. The minimum follow-up was 12 months (range, 12 to 85 months, with an average of 38 months). The central incisors were tested for percussion sound, mobility, and pulpal response to electric stimulation, and then compared with the lateral incisors. The pocket depths and the height of the alveolar bone were measured, and the root surface was evaluated for resorption on radiographs. RESULTS: Percussion and mobility tests indicated normal values for all teeth. Four (11%) of the central incisors did not respond to electrical stimulation. There was no difference in pocket depth between the mesial and distal sulci of the central incisors. In one tooth, resorption was detectable on the medial surface of the root. Minor root surface injury was seen in two roots, although these injuries were not progressive. The alveolar bone level of the central incisors was located slightly more superiorly on the mesial than on the distal side. CONCLUSIONS: Although there may be some minor complications to the periodontal and pulpal tissues after combined Le Fort I and midline osteotomies, the harmful effects seem to be of negligible clinical significance.

Adolescent↗

Pneumoperitoneum in healthy humans does not affect central blood volume or cardiac output.

BACKGROUND: This study addresses the question of whether the elevation of the mean arterial pressure and central venous pressure in response to pneumoperitoneum for laparoscopic surgery is caused by increases in central blood volume and/or cardiac output. METHODS: Eleven patients in good cardiopulmonary health and scheduled for laparoscopic cholecystectomy, with a mean age of 42 years, were included. After induction of anaesthesia with fentanyl and propofol, radial arterial and central venous lines were introduced. The central blood volume and cardiac output were determined by the indicator-dilution technique, using inline densitometric measurements of indocyanine green (ICG). The measurements were made before and after the establishment of pneumoperitoneum by insufflation of carbon dioxide to an intra-abdominal pressure level of 11-13 mmHg. RESULTS: The mean arterial pressure (62+/-6 mmHg) increased after induction of pneumoperitoneum by 40+/-26% (P<0.05) and the central venous pressure increased from 6+/-4 mmHg to 8+/-6 mmHg (P<0.05). The cardiac output (4.3+/-0.9 L/min) and central blood volume (1.5+/-0.5 L) were not affected by the induction of pneumoperitoneum. CONCLUSIONS: In healthy anaesthetized subjects, the elevation of mean arterial pressure and central venous pressure in response to pneumoperitoneum was not caused by enhancement in cardiac output or central blood volume.

Adult↗

Confirmed quantitative trait loci for fatness and growth on pig chromosome 4.

Quantitative trait loci (QTLs) with large effects on fatness and growth have been identified previously on pig chromosome 4 in an intercross between the European wild pig and Large White domestic pigs. Two F2 sows, heterozygous for the actual chromosome region, were backcrossed to a Large White boar, and two backcross (BC1) boars were in turn backcrossed to Large White/Landrace sows. One of the boars was heterozygous for an intact wild pig-derived QTL region, whereas the other carried a recombinant haplotype. A total of 85 BC2 animals were produced. Phenotypical measurements included daily weight gain, ultrasonic measurements of fat depth at 70 and 90 kg and several carcass traits. QTL segregation was deduced using 15 markers previously assigned to chromosome 4. Highly significant QTL effects were observed on all fatness traits and on the length of the carcass. A small but significant effect on growth was also observed. The results confirm the presence of one or more QTLs on chromosome 4 affecting fatness and growth. There was a good agreement between the estimates of QTL effects in the F2 and BC2 generations. The results from the recombinant sire family allowed us to map the major QTL effect distal to the recombination breakpoint. We propose that this confirmed QTL with a major effect on fatness is designated FAT1.

Adipose Tissue↗

Heterozygosity excess at the cattle DRB locus revealed by large scale genotyping of two closely linked microsatellites.

A method for MHC DRB typing in cattle based on two closely linked and highly polymorphic microsatellites is described. The two microsatellites DRBP1ms and DRB3ms are located in intron 2 of the corresponding DRB gene. The very strong linkage disequilibrium between the two loci made it possible to establish DRB microsatellite haplotypes. The typing results with this method on reference samples followed closely that obtained with RFLP and direct sequence analysis of DRB3 exon 2. The method is well suited for large scale genotyping and was successfully applied for typing more than 600 unrelated animals representing 23 breeds. The data were used to test whether the observed DRB allele frequency distributions were consistent with that expected for selectively neutral alleles in populations at mutation-drift equilibrium. A significant heterozygosity excess was detected and there was an obvious trend across breeds towards a more even allele frequency distribution than expected. The deviation may be due to balancing selection acting on the DRB locus or by recent population bottlenecks.

Alleles↗

Intensive rehabilitation of emotionally distressed patients after coronary by-pass grafting.

OBJECTIVES: To evaluate whether the status of emotionally distressed post coronary by-pass surgery patients can be improved by a comprehensive, in-patient rehabilitation programme. DESIGN: Cross-sectional. SETTING: Rehabilitation hospital. SUBJECTS: One hundred and fifty-two post coronary by-pass surgery patients referred to an intensive rehabilitation programme. The study group was divided into two subgroups, according to the level of emotional distress. Forty-three (30%) out of 142 patients who completed the Nottingham Health Profile were considered to be distressed. INTERVENTIONS: The comprehensive 4-week inpatient rehabilitation programme consisted of daily physical exercise, lectures about coronary disease and risk factors, psychological support and nutrition counselling. MAIN OUTCOME MEASURES: Physical fitness, blood lipids and quality of life questionnaires. RESULTS: The two-way analysis of variance showed that emotionally distressed patients achieved equally good results as those obtained by nondistressed patients in performance regarding the maximal exercise stress test, maximum rate pressure product achieved, or the level of resting heart rate. Significant improvement in psychological well-being as assessed by a seven-point rating scale was observed in both groups. Both groups of patients were also equally successful in weight reduction and lowering of total cholesterol and triglycerides. Of all the patients who were employed at admission, twice the number of patients in the distressed group were in receipt of a permanent disability pension and half the number of patients was employed, compared to the initially nondistressed group, at 1-year follow-up. CONCLUSIONS: Distressed patients were very successful in improving their functional status and reducing risk factors when offered an intensive rehabilitation programme but they were much less successful in returning to work. Secondly, patients who were emotionally distressed after surgery did not differ in regard to disease status or physical capacity from nondistressed patients. They did, however, experience more angina pectoris both in daily life and when exposed to a maximal exercise stress test. Finally, the presence of emotional distress was easily detected by any measure of psychological status.

Adult↗

A prospective randomized study of a dental appliance compared with uvulopalatopharyngoplasty in the treatment of obstructive sleep apnoea.

The enthusiasm for uvulopalatopharyngoplasty (UPPP) in the treatment of obstructive sleep apnoea (OSA) has declined in recent years, partly because of a lower success rate over time and partly because of adverse effects. Reports on the beneficial effects of dental appliances exist, but only one prospective randomized study has been published comparing dental appliances with nasal continuous positive airway pressure (CPAP) treatment. No study has been published comparing dental appliance treatment with UPPP. Ninety-five male patients with confirmed OSA, subjective daytime sleepiness and an apnoea index (AI) > 5 were randomized for subsequent treatment with either a dental appliance or UPPP. There were 49 patients in the dental appliance group and 46 in the UPPP group. Thirty-seven patients in the dental appliance group and 43 in the UPPP group completed the 12-month follow-up. The success rate (rate of patients with at least a 50% reduction in AI) for the dental appliance group was 95%, which was significantly higher (p < 0.01) than the 70% success rate for the UPPP group. According to the criteria for OSA (apnoea index > or = 5 or apnoea/hypopnoea index > or = 10), 78% of the dental appliance group and 51% of the UPPP group were normalized after 12 months. The difference between the groups was significant (p < 0.05). These findings suggest that the dental appliance technique is useful in the treatment of mild to moderate OSA.

Humans↗

Monomorphism and polymorphism at Mhc DRB loci in domestic and wild ruminants.

Genetic polymorphism at Mhc class II DRB loci was investigated in samples of musk-ox from Canada and Greenland; moose from Sweden, Norway, Canada, and Alaska; roe deer from Norway and Sweden; reindeer from Svalbard and Norway; fallow deer from Norway and Sweden; and red deer from Norway. The results were compared with published data on cattle, bison, goat, sheep, and red deer. Cattle-specific primers amplified a single DRB locus in all species except fallow deer and red deer, in which two loci were found. Single strand conformation polymorphism analysis and DNA sequence analysis were employed to detect genetic polymorphism. Complete monomorphism was found in musk-ox and fallow deer. Limited polymorphism was found in the moose, roe deer, and reindeer from Svalbard, whereas intermediate to extensive DRB diversity was present in reindeer from Norway and in bison, sheep, goat, cattle, and red deer. The restricted Mhc diversity in moose, roe deer, and fallow deer is notable in relation to the dramatic population expansion of moose and roe deer in Sweden during this century and since fallow deer is used for meat and game production with good results and without any marked disease problems. The results question the view that species or populations with restricted Mhc diversity have poor resistance to infectious diseases. A phylogenetic tree analysis revealed a clustering of DRB sequences within species rather than within allelic lineages across species. The results suggest trans-species persistence of polymorphic sequence motifs rather than of allelic lineages.

Amino Acid Sequence↗

The problem of dentoalveolar ankylosis and subsequent replacement resorption in the growing patient.

Dentoalveolar ankylosis is a serious complication following injuries of the periodontal membrane in severe dental trauma such as avulsion and intrusion. The condition is a fusion of the alveolar bone with the tooth. The consequences of this condition are progressive resorption of the root with replacement by bone (replacement resorption) and arrested growth of the alveolar process in the growing patient. This article will present an overview of dentoalveolar ankylosis and replacement resorption and its problems, treatment options and prognosis, especially focusing on the growing patient.

Adult↗

Reliability of breath-alcohol analysis in individuals with gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is widespread in the population among all age groups and in both sexes. The reliability of breath alcohol analysis in subjects suffering from GERD is unknown. We investigated the relationship between breath-alcohol concentration (BrAC) and blood-alcohol concentration (BAC) in 5 male and 5 female subjects all suffering from severe gastroesophageal reflux disease and scheduled for antireflux surgery. Each subject served in two experiments in random order about 1-2 weeks apart. Both times they drank the same dose of ethanol (approximately 0.3 g/kg) as either beer, white wine, or vodka mixed with orange juice before venous blood and end-expired breath samples were obtained at 5-10 min intervals for 4 h. An attempt was made to provoke gastroesophageal reflux in one of the drinking experiments by applying an abdominal compression belt. Blood-ethanol concentration was determined by headspace gas chromatography and breath-ethanol was measured with an electrochemical instrument (Alcolmeter SD-400) or a quantitative infrared analyzer (Data-Master). During the absorption of alcohol, which occurred during the first 90 min after the start of drinking, BrAC (mg/210 L) tended to be the same or higher than venous BAC (mg/dL). In the post-peak phase, the BAC always exceeded BrAC. Four of the 10 subjects definitely experienced gastric reflux during the study although this did not result in widely deviant BrAC readings compared with BAC when sampling occurred at 5-min intervals. We conclude that the risk of alcohol erupting from the stomach into the mouth owing to gastric reflux and falsely increasing the result of an evidential breath-alcohol test is highly improbable.

Adult↗

Effects and adverse events of a dental appliance for treatment of obstructive sleep apnoea.

In a prospective study, 95 patients with mild to moderate obstructive sleep apnoea (OSA) were randomised to receive either surgical treatment, uvulopalatopharyngoplasty, (4-6 patients) or treatment with a nocturnal dental appliance for mandibular advancement (49 patients). Of the 49 dental appliance patients, 37 completed the 12-month follow-up. The aim of this study was to evaluate the effects and adverse events of dental appliance treatment from a one-year perspective. Somnography was employed to measure treatment effects before and 12 months post-treatment. At the 12-month control, somnography was performed twice: the first time with the dental appliance and the second time without it. Adverse events were recorded 2 weeks and 3, 6, and 12 months after treatment was initiated. The patients used the dental appliance on average 6 nights/week. After 12 months of treatment, the apnoea, apnoea/hypopnoea, oxygen desaturation, and snoring indices decreased significantly. Ninety-five per cent of the patients reduced their apnoea index by > or = 50% and 78% of the patients were normalised following treatment. At the somnographic registration without the dental appliance, the values were found comparable to what they were before treatment. Mandibular mobility and occlusion were constant throughout the study. The adverse events resulting from using the dental appliance were relatively minor and infrequent, and no serious complications were observed except for two patients who reported pain from the temporomandibular joint. In conclusion, the dental appliance has been shown to be a valuable treatment method for mild to moderate OSA with few adverse events in the stomatognathic system or other complications.

Adult↗

Gender differences in psychological reactions to infertility among couples seeking IVF- and ICSI-treatment.

BACKGROUND: Gender differences and similarities in psychological reactions related to infertility, perception of social support, the effect of infertility on the marital relationship and coping-style were investigated among Swedish couples seeking in vitro fertilization -- or intracytoplasmic sperm injection - treatment. METHODS: Ninety-one couples entering treatment completed the Infertility Reaction Scale, a self-report questionnaire with structured and open-ended questions and the Miller Behavioral Style Scale. RESULTS: The women reacted more strongly to their infertility than the men as measured by the Infertility Reaction Scale (p<0.05). Factor analysis of the Infertility Reaction Scale produced three factors for men and women respectively. The first factor that emerged for the men was 'The male role and social pressure' and the second factor was 'The major focus of life'. For the women the two first factors were reversed compared to those of the men. The third factor 'Effect on sexual life' was similar for men and women. Significantly more men than women had not confided in anyone about their infertility problem (p<0.001). The information-seeking coping style was significantly correlated with infertility distress only among men (p<O.05). CONCLUSION: The women reacted more strongly to their infertility than the men and they felt an intense desire to have a child. They received more social support than their partners, who experienced the fulfillment of the male role as well as the social role to become a parent as the most central aspects of infertility. The information-seeking coping style was significantly correlated with infertility distress only among men.

Adult↗