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Biomedical subjects

K Andersson

Publications and source records attributed to K Andersson.

At least 91 records · Page 5Linked to original sources

Release of endogenous excitatory amino acids in the neostriatum of the rat under physiological and pharmacologically-induced conditions.

There is immunohistochemical evidence suggesting that glutamate (Glu) is released from nerve terminals and acts, via several receptor subtypes, as a major excitatory neurotransmitter in the cortico-striatal pathway of the rat. Aspartate (Asp) is also present in cortico-striatal neurons, but its role as a neurotransmitter has been questioned, since, in contrast to Glu, it has not been demonstrated in presynaptic vesicles. Glu and Asp can be found at submicroM concentrations in the extracellular compartment of most areas of the basal ganglia. Their concentrations are largely regulated by transport mechanisms, but also by a synaptotagmin-dependent exocytotic release, and are sufficiently high to occupy junctional and extrajunctional receptors. We have investigated whether Glu and Asp release in the neostriatum can be selectively modulated by different neuronal systems. Dopamine (DA) and cholecystokinin (CCK) selectively stimulate Asp release, via D1 and CCKB receptor subtypes, respectively. Also opioid kappa-agonists increase Asp release. We propose that the selective modulation of Asp release by D1-, CCKB- and kappa-agonists involves striatal neurons containing Asp, but not Glu. In contrast, local perfusion with the mu-opioid antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) increases both Glu and Asp release. This effect is probably exerted on cortico-striatal terminals, via presynaptic inhibitory mu-receptors. Thus, these results demonstrate that extracellular levels of Glu and Asp are modulated differentially by different neuronal systems, and suggest that in the neostriatum of the rat there are neuronal populations using Glu and/or Asp as messenger(s).

Animals↗

ECL cells of the rat stomach: development of lipofuscin in response to sustained gastrin stimulation.

Ageing cells, especially post-mitotic cells, are known to accumulate pigments, i.e. highly electron-dense material, referred to as ceroid or lipofuscin. This material is formed as a consequence of autophagocytosis and peroxidation of the products undergoing degradation. The present study describes the development of lipofuscin in the ECL cells of the rat stomach. These cells produce and secrete histamine in response to gastrin. They are rich in secretory vesicles, which fuse to form vacuoles in hypergastrinaemic rats. Hypergastrinaemia was induced by continuous infusion of human Leu15-gastrin-17 for 6 days or by daily treatment with omeprazole for 10 weeks. Either treatment caused both vacuoles and lipofuscin bodies to appear in large numbers; the vacuoles disappeared promptly after interruption of the hypergastrinaemia, whereas the lipofuscin bodies remained. Antrectomy-evoked hypogastrinaemia was associated with a reduced number and volume density of lipofuscin bodies. Treatment with alpha-fluoromethylhistidine, an irreversible inhibitor of the histamine-forming enzyme, resulted in depletion of ECL-cell histamine and was found to prevent the omeprazole-evoked formation of vacuoles and lipofuscin. The numbers of both vacuoles and lipofuscin bodies were well-correlated with the serum gastrin concentration, suggesting that gastrin stimulates the development not only of vacuoles but also of lipofuscin, perhaps through enhanced autophagocytosis and/or oxidative stress. Thus, lipofuscin bodies may develop from vacuoles, and both vacuoles and lipofuscin bodies may reflect the efforts of overstimulated ECL cells to cope with the excessive formation of secretory products.

Animals↗

Perforations with intrauterine devices. Report from a Swedish survey.

This survey comprised 50 consecutive perforations occurring with intrauterine devices (IUD) reported to the National Patient Insurance Scheme Register during 1990 to 1993. All 50 women were parous and > 20 years of age at the time of IUD insertion. Forty-two (84%) of the IUD were inserted by a midwife and eight by a gynecologist. A total of 45 women (90%) had their IUD inserted < 1 year after a full-term pregnancy and 31 women (62%) had their IUD inserted < or = 12 weeks after delivery. Of the 50 women, 27 (54%) reported that they were breastfeeding at the time of IUD insertion. No particular IUD was overrepresented in relation to its share on the market. In 31 cases (62%), severe pain at insertion and during the first 24 h was recorded. In 14 women (28%), the perforation was diagnosed early (i.e., within 1 month of insertion) and in 36 women (72%), the perforation was diagnosed > 1 month after insertion. Lower abdominal pain was the most frequent symptom at early diagnosis but in two cases, the main symptom was heavy bleeding. Among the 36 women in whom the perforation was discovered more than 1 month after insertion, the diagnosis was made when an unexpected pregnancy occurred in 20 women (56%). In 15 cases, the IUD strings were not visible during pelvic examination at a routine check-up, which led to efforts to locate the IUD. Thirty-two women (64%) underwent laparotomy for removal. We conclude that lactating women seem to be a risk group for perforation and that a national register of IUD perforations could provide a better means of quality control.

Abdominal Pain↗

Determination of aflatoxicol in human urine by immunoaffinity column clean-up and liquid chromatography.

A method for the determination of aflatoxicol in urine has been developed. The urine samples were cleaned up by an automated procedure using immunoaffinity columns before analysis by high-performance liquid chromatography and fluorescence detection. Post-column derivatization with bromine allowed the simultaneous determination of aflatoxicol and aflatoxins B1, B2, G1, G2, M1, and Q1. Average recovery of aflatoxicol was 99% in the range 4-40 pg ml-1 of spiked urine samples. The relative standard deviations were all between 1% and 3%. The limit of detection was 1 pg ml-1 urine. Authentic samples from exposed feed-factory workers were analysed, but aflatoxin levels were found to be below the detection limit.

Aflatoxins↗

Etiology and treatment of psychogenic voice disorder: results of a follow-up study of thirty patients.

It is generally accepted that psychogenic voice disorder (PVD) is a result of psychosocial stress; however, systematic studies of etiological factors in this condition are few. Furthermore, although immediate effects of therapy are estimated to be good, relapses are frequent, and the long-term effects of therapy are not known. The present prospective and longitudinal study on 30 patients was thus focused on possible etiological factors, the course of therapy, and the long-term results of therapy for PVD. The results indicate that interpersonal conflicts related to family and work are of basic importance in precipitating this condition. PVD is interpreted as a specific disorder of verbal emotional expression. Our therapy model in which vocal exercises are performed, together with training of communicative skills, seems rewarding. Relapses were not reported in 88% of the patients during the followup period of 1.9-8.4 years after therapy.

Adolescent↗

Investigation into thiol conjugation of transthyretin in hereditary transthyretin amyloidosis.

BACKGROUND: For all forms of amyloidosis, the amyloid-generating mechanism is unknown. Familial amyloidotic polyneuropathy type I is caused by a variant transthyretin (TTR Met-30). As electrospray ionization mass spectrometry (ESI-MS) discloses both thiol-conjugated and -unconjugated forms of wild-type and variant TTR, we wanted to investigate the relationship between TTR conjugation and clinically overt amyloid disease. METHODS: Plasma from 35 individuals (12 symptomatic TTR Met-30 carriers, nine asymptomatic and 14 healthy control subjects) were analysed using ESI-MS. RESULTS: The total TTR concentration was significantly lower in symptomatic TTR Met-30 carriers than in control subjects. An increased percentage of conjugated TTR Met-30 was found in symptomatic carriers compared with asymptomatic, whereas the percentage conjugated wild-type TTR was similar for control subjects, asymptomatic and symptomatic TTR Met-30 carriers. CONCLUSION: The finding of a decreased ratio of unconjugated to conjugated TTR Met-30 in plasma samples from symptomatic TTR Met-30 carriers indicates that thiol conjugation of TTR could be involved in amyloid formation.

Adult↗

Factors associated with cirrhosis development in chronic hepatitis C patients from an area of low prevalence.

The aim of this study was to evaluate the importance of different endogenous and exogenous factors associated with cirrhosis development among hepatitis C virus (HCV)-positive individuals from an area of low prevalence. We studied 106 consecutive HCV RNA positive patients who had undergone liver biopsy. Each patient was assessed with special attention to risk factors for hepatitis C infection, average daily alcohol consumption and analysis of plasma levels of alpha1-antitrypsin (alpha1AT) and alpha1-antichymotrypsin (alpha1ACT). Viral RNA, amplified from serum with the polymerase chain reaction (PCR) technique, was used for genotyping. Liver biopsies were assessed according to conventional histopathological criteria, and for necroinflammatory activity (grade) and fibrosis (stage) according to a numerical scoring system. The presence of cirrhosis (stage 4) was used as the dependent variable in multivariate logistic regression analysis. Alcohol abuse (P = 0.007), age at entry (P < 0.001), immigrant status (P = 0.017) and a low alpha1ACT level (P = 0.008) were all independent determinants of progression to cirrhosis whereas HCV genotype 1, estimated duration of HCV infection and positivity for antibodies to hepatitis B core antigen (HBcAb) were not. Cirrhosis occurred at a significantly younger age (P = 0.00(5) among alcohol abusers. Hence, both endogenous and exogenous factors such as subnormal alpha1ACT levels and alcohol appear to contribute to the rate of progression to cirrhosis among HCV-positive patients.

Adult↗

Multiple marker mapping of quantitative trait loci in a cross between outbred wild boar and large white pigs.

A quantitative trait locus (QTL) analysis of growth and fatness data from a three generation pig experiment is presented. The population of 199 F2 animals was derived from a cross between wild boar and Large White pigs. Animals were typed for 240 markers spanning 23 Morgans of 18 autosomes and the X chromosome. A series of analyses are presented within a least squares framework. First, these identify chromosomes containing loci controlling trait variation and subsequently attempt to map QTLs to locations within chromosomes. This population gives evidence for a large QTL affecting back fat and another for abdominal fat segregating on chromosome 4. The best locations for these QTLs are within 4 cM of each other and, hence, this is likely to be a single QTL affecting both traits. The allele inherited from the wild boar causes an increase in fat deposition. A QTL for intestinal length was also located in the same region on chromosome 4 and could be the same QTL with pleiotropic effects. Significant effects, owing to multiple QTLs, for intestinal length were identified on chromosomes 3 and 5. A single QTL affecting growth rate to 30 kg was located on chromosome 13 such that the Large White allele increased early growth rate, another QTL on chromosome 10 affected growth rate from 30 to 70 kg and another on chromosome 4 affected growth rate to 70 kg.

Animals↗

Affinity selection and repertoire shift: paradoxes as a consequence of somatic mutation?

Affinity selection of antibodies during immune responses relies on two mechanisms, one molecular that involves the targeted introduction of somatic mutations into rearranged immunoglobulin genes and one cellular that involves the clonal expansion of B cells expressing a surface immunoglobulin with a higher affinity for antigen compared to their competitors. In this review we focus on the conditions for affinity selection during the establishment, expansion and memory phases of the immune response. We postulate that somatic mutation evolved prior to affinity selection and we present a model for selection of B cells in germinal centres. We also discuss the possibility that antibody repertoire shift occurs during the memory maintenance phase. Finally, we argue that a significant affinity selection and a selection for polyclonality of immune responses occur during this stage of the immune response.

Animals↗

Surgical trauma decreases glutathione synthetic capacity in human skeletal muscle tissue.

To gain insight into cellular metabolism underlying the glutathione (GSH) alterations induced by surgical trauma, we assessed postoperative skeletal muscle GSH metabolism and its redox status in 10 patients undergoing elective abdominal surgery. Muscle biopsy specimens were taken from the quadriceps femoris muscle before and at 24 and 72 h after surgery. GSH concentrations decreased by 40% at 24 h postoperatively compared with the paired preoperative values (P < 0.001) and remained low at 72 h (P < 0.01). The concentration of GSH disulfide (GSSG) did not significantly change throughout the study period, whereas the total GSH (as GSH equivalent) concentration decreased after surgery. Of the GSH constituent amino acids, the concentration of cysteine remained unchanged throughout the study period (from 28.2 +/- 10.1 preoperatively to 29.4 +/- 13.9 at 24 h postoperatively and to 28.3 +/- 15.6 micromol/kg wet wt at 72 h postoperatively). Despite a reduction in glutamate concentration by 40% 24 h after surgery, no correlation was established between GSH and glutamate concentrations postoperatively. Activity of gamma-glutamylcysteine synthetase did not change significantly after surgery, whereas GSH synthetase activity decreased postoperatively (from 66.4 +/- 19.1 preoperatively to 41.0 +/- 10.5 24 h postoperatively, P < 0.01, and to 46.0 +/- 11.7 microU/mg protein 72 h postoperatively, P < 0.05). The decrease of GSH was correlated to the reduced GSH synthetase activity seen at 24 h postoperatively. These results indicate that the skeletal muscle GSH pool is diminished in patients after surgical trauma. The depletion of the GSH pool is associated with a decreased activity of GSH synthetase, indicating a decreased GSH synthetic capacity in skeletal muscle tissue.

Aged↗

Mapping quantitative trait loci for carcass and meat quality traits in a wild boar x Large White intercross.

An intercross between wild boar and a domestic Large White pig population was used to map quantitative trait loci (QTL) for body proportions, weight of internal organs, carcass composition, and meat quality. The results concerning growth traits and fat deposition traits have been reported elsewhere. In the present study, all 200 F2 animals, their parents, and their grandparents were genotyped for 236 markers. The marker genotypes were used to calculate the additive and dominance coefficients at fixed positions in the genome of each F2 animal, and the trait values were regressed onto these coefficients in intervals of 1 cM. In addition, the effect of proportion of wild boar alleles was tested for each chromosome. Significant QTL effects were found for percentage lean meat and percentage lean meat plus bone in various cuts, proportion of bone in relation to lean meat in ham, muscle area, and carcass length. The significant QTL were located on chromosomes 2, 3, 4, and 8. Each QTL explained 9 to 16% of the residual variance of the traits. Gene action for most QTL was largely additive. For meat quality traits, there were no QTL that reached the significance threshold. However, the average proportion of wild boar alleles across the genome had highly significant effects on reflectance and drip loss. The results show that there are several chromosome regions with a considerable effect on carcass traits in pigs.

Animals↗

Swedish gynecologists' and general practitioners' views on the climacteric period: knowledge, attitudes and management strategies.

AIMS: To investigate attitudes, knowledge and management strategies concerning hormone replacement therapy (HRT) among gynecologists and general practitioners (GPs) in Sweden. MATERIAL AND METHODS: In 1996 a questionnaire was sent to all Swedish gynecologists (n=1323) and every third general practitioner (GP) (n=1397) regarding indications, contraindications, treatment regimens and their own (or their wives') use of estrogens. RESULTS: Answers were received from 53% of the GPs and from 80% of the gynecologists. Fifteen per cent of the GPs often considered it difficult to evaluate the advantages and disadvantages of hormone replacement therapy compared to 2% of the gynecologists (p<0.001). Almost 100% of the physicians considered hot flushes, night sweats and osteoporosis to be indications for HRT. Significantly more GPs compared to gynecologists (50% vs 24%) stated that estrogen increased the risk of developing a deep vein thrombosis. Significantly more GPs performed measurements of blood pressure, weight, lipoproteins and palpated the breasts before starting treatment and at the follow-up visits. Significantly more gynecologists performed pelvic examination, vaginal sonography, endometrial biopsy and mammography. Among the female doctors who were either postmenopausal or had climacteric symptoms 72% of the GPs and 88% of the gynecologists were current users of HRT (p<0.01). Corresponding figures for the wives were 68% vs 86% (p<0.001). CONCLUSION: As earlier contraindications to HRT nowadays have turned into indications it is reasonable that more GPs compared to gynecologists consider it difficult to evaluate advantages and disadvantages of HRT and more gynecologists than GPs took the first initiative to discuss HRT with their patients. The information that far more female doctors and doctors' wives, compared to the Swedish female population, were using HRT is important information when discussing HRT compliance with patients.

Adult↗

Short- and long-term effects of perinatal asphyxia on monoamine, amino acid and glycolysis product levels measured in the basal ganglia of the rat.

The effects of perinatal asphyxia on levels of dopamine (DA) and its metabolites, amino acids and glycolysis products, measured in tissue samples from substantia nigra (SN), striatum, ventral tegmental area (VTA), and nucleus accumbens (Acb), were studied 80 min to 8 days after birth with high performance liquid chromatography (HPLC). Furthermore, extracellular levels of DA, amino acids and glycolysis products were measured with in vivo microdialysis in the striatum 40-140 min and 4 weeks after birth. Asphyxia was induced by immersing foetus-containing uterus horns, removed from ready-to-deliver Sprague-Dawley rats, in a water bath at 37 degrees C for various time periods (0-22 min). Spontaneous- and caesarean-delivered pups were used as controls. Perinatal asphyxia led to a decrease in the rate of survival, depending upon the length of the insult. In parallel, lactate (LACT) levels were increased with the length of the insult in all examined brain regions, monitored ex vivo or in vivo immediately after birth. DA, glutamate (GLU) and aspartate (ASP) levels were also increased, mainly in tissue samples taken from the mesencephalon. Only minor changes were observed in tissue samples taken from the telencephalon. However, in experiments with in vivo microdialysis, DA and GLU levels were increased following 20-21 and 21-22 min of perinatal asphyxia, but the effect of K+ depolarisation on extracellular DA and ASP levels was strongly diminished. DA and metabolites increased with development in SN and striatum, with no clear differences between control and asphyctic rats. However, 8 days after birth, it was found that DA levels were increased, alternatively decreased in mesencephalic and telencephalic regions following 20-21 and 21-22 min of perinatal asphyxia, periods associated with 60% and 90% of perinatal mortality, respectively. Furthermore, in microdialysis experiments performed 4 weeks after birth, extracellular DA and its metabolites levels were also increased, alternatively decreased in rats exposed to a 20-21 and 21-22 min perinatal asphyctic insult. In this last group, GLU and ASP levels were also decreased. Furthermore, the effect of K+ depolarisation on DA and ASP levels was strongly decreased in both asphyctic groups. Thus, perinatal asphyxia produces short- and long-term consequences in general metabolism, and induces region-specific changes in several neurotransmitter systems, mainly affecting meso-telencephalic DA systems.

Acute Disease↗

Effect of Solvent Quality on Reverse Micelle Formation and Water Solubilization by Poly(ethylene oxide)/Poly(propylene oxide) and Poly(ethylene oxide)/Poly(butylene oxide) Block Copolymers in Xylene

In addition to associating into ("normal") micelles in aqueous solutions, amphiphilic polyoxyalkylene block copolymers can form "reverse" micelles in organic solvents at sufficiently high copolymer concentrations (above the critical micellization concentration (CMC)) and in the presence of some water. The effects of solvent quality on the copolymer micellization in an organic solvent and on the solubilization of water in such systems are examined here for representative poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO) and poly(butylene oxide)-b-poly(ethylene oxide) (PBO-PEO) copolymers. The solvent quality is modulated by the addition of cosolutes and by a change in the temperature. A number of notable observations are reported: Worsening the aqueous solvent conditions by the addition of NaCl (10 wt% with respect to water) almost doubles the CMC and the water solubilization capacity (WS) of a PEO-PPO-PEO copolymer in p-xylene. An increase in temperature makes water a worse and xylene a better solvent for the copolymer. The combined result of heating is an increase of the CMC for all three copolymers studied. This indicates that the formation of reverse micelles is exothermic, which is opposite to what has been observed for normal micelles. The effects of temperature on the water uptake are nonmonotonic: WS increased with temperature for a PEO-PPO-PEO copolymer with 40% PEO but decreased for a copolymer with 20% PEO. An increase in WS with temperature, followed by a decrease, with the maximum WS efficiency occurring at the "effective" cloud point of the copolymer is proposed in order to explain this observation. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗

Characterization of two highly amyloidogenic mutants of transthyretin.

The plasma protein transthyretin (TTR) has the potential to form amyloid under certain conditions. More than 50 different point mutations have been associated with amyloid formation that occurs only in adults. It is not known what structural changes are introduced into the structure of this otherwise stable molecule that results in its aggregation into insoluble amyloid fibrils. On the basis of calculations of the frequency of known mutations over the polypeptide, we have constructed two mutants in the D-strand of the polypeptide. These molecules, containing either a deletion or a substitution at amino acid positions 53-55, were unstable and spontaneously formed aggregates upon storage in TBS (pH 7.6). The precipitates were shown to be amyloid by staining with thioflavin T and Congo Red. Their ultrastructure was very similar to that of amyloid fibrils deposited in the vitreous body of patients with familial amyloidotic polyneuropathy type 1 with an amino acid replacement in position 30 (TTRmet30). Like amyloid isolated from the vitreous body of the eye, the amyloid precipitates generated from the TTR mutants exposed a trypsin cleavage site between amino acid residues 48 and 49, while plasma TTRmet30 isolated from amyloidosis patients as well as wild-type TTR only showed minor trypsin sensitivity. Our data indicate that the mutants we have constructed are similar to amyloid precursors or may share structural properties with intermediates on a pathway leading to amyloid deposits of plasma TTR.

Amyloid↗

Quality control of two rose bengal and modified DRBC and DG18 media.

The effect of storage on the performance of four mycological media, DG18, DRBC and two Rose Bengal agars, one from Difco, the other recommended by the Swedish Standard Institution, was investigated. The autoclaved media were stored (+4 degrees C) in the dark for up to 26 weeks. Following each storage period, the media were remelted and poured and the plates stored (+4 degrees C) in the dark for a maximum of 8 weeks before inoculation with test microorganisms. All media contained antibiotics. Both rapidly and slowly growing moulds, and also yeasts and bacteria were used as test microorganisms. No distinct effect of storage time on colony appearance could be shown for any of the four media. If the loss of restricted growth of Rhizopus stolonifer is used as a measure of the performance of the media, DRBC plates should not be stored for longer than 2 weeks after being poured from fresh medium. Storage of DRBC in flasks should not exceed 4 weeks and plates prepared from this medium should not be kept for more than 1 week. DG18 plates should only be poured from fresh medium and kept for a maximum of 1 week. The inhibitory effect of the antibiotic supplement on bacteria lasted for at least 4 weeks in DG18 and the two rose bengal media.

Agar↗