Biomedical subjects

A Andersson

Publications and source records attributed to A Andersson.

At least 19 recordsLinked to original sources

PubMed2002

Desaturation and elongation of Fatty acids and insulin action.

Insulin resistance is characterized by specific changes of the composition of fatty acids in the serum lipids and in the skeletal muscle membranes. Impaired insulin sensitivity is associated with high proportions of palmitic (16:0) acid and low levels of linoleic (18:2 n-6) acid in serum. In addition, there are apparent changes of the fatty acid desaturase activities, suggesting an increased activity of the Delta9 and Delta6 desaturases and a decreased activity of the Delta5 desaturase. The activity of the fatty acid desaturases is regulated by long-chain polyunsaturated fatty acids and insulin and is probably also dependent on the degree of physical activity. A high ratio between arachidonic (20:4 n-6) and dihomo-gamma linolenic (20:3 n-6) acid, as a measure of Delta5 desaturase activity, in the skeletal muscle phospholipids has been related to good insulin sensitivity. Available knowledge seems to indicate that the degree of saturation of the body lipids, and especially the proportion of palmitic acid in the lipid membranes, may be critical for insulin sensitivity. The strong relationships between the Delta5 desaturase activity, a high content of long-chain polyunsaturated fatty acids in the skeletal muscle, and insulin sensitivity may be due to parallel effects of diet and/or physical activity on the fatty acid composition and on insulin sensitivity.

Dietary Fats↗

PubMed2001

The effect of host factors and capsule composition on the cellular overgrowth on implanted alginate capsules.

Microencapsulation of islets of Langerhans in alginate/poly-L-lysine (PLL)/alginate capsules may provide a method for transplantation in the absence of immunosuppression. The aim of this study was to investigate the problem of overgrowth on implanted capsules with regard to the composition of the capsules and host factors such as cytokine and nitric oxide production. Empty capsules were implanted to C57BL/6 mice for 1, 3, 7, or 28 days. Glucose oxidation rates showed the metabolic activity of the cellular overgrowth on retrieved capsules. DNA content, histological score, and retrieval rates were also measured to assess the overgrowth. It was noted that the pericapsular host reaction arose by day 7 and had not increased further by day 28. Capsules of varying alginate compositions and different concentrations of PLL were implanted for 7 days to either C57BL/6 or Balb/c mice. Capsules were also implanted to mice lacking the inducible nitric oxide synthase enzyme. Glucose oxidation rates, DNA content, and histological score were positively correlated to each other and negatively correlated to retrieval rates. The pericapsular reaction was reduced if PLL was omitted from the capsule or if a high mannuronic acid alginate was used. Balb/c mice had reduced cellular overgrowth on implanted capsules and had reduced mRNA expression of interleukin-1 beta and tumor necrosis factor-alpha in their peritoneal macrophages. The capsular overgrowth seemed more severe in animals lacking inducible nitric oxide synthase compared with wild-type controls. It is concluded that alginate composition, PLL, and recipient factors such as nitric oxide production and cytokine expression affect the cellular overgrowth on implanted alginate capsules.

Alginates↗

PubMed2001

A transcriptional roadmap to wood formation.

The large vascular meristem of poplar trees with its highly organized secondary xylem enables the boundaries between different developmental zones to be easily distinguished. This property of wood-forming tissues allowed us to determine a unique tissue-specific transcript profile for a well defined developmental gradient. RNA was prepared from different developmental stages of xylogenesis for DNA microarray analysis by using a hybrid aspen unigene set consisting of 2,995 expressed sequence tags. The analysis revealed that the genes encoding lignin and cellulose biosynthetic enzymes, as well as a number of transcription factors and other potential regulators of xylogenesis, are under strict developmental stage-specific transcriptional regulation.

Cell Wall↗

PubMed2001

The H2-Ab gene influences the severity of experimental allergic encephalomyelitis induced by proteolipoprotein peptide 103-116.

Immunization of H2(p) and H2(q) congenic C3H mouse strains with the PLP 103-116 peptide elicited two distinct experimental allergic encephalomyelitis (EAE) disease courses. C3H.Q (H2(q)) mice developed an acute-phase disease with classical ascending paralytic signs whereas C3H.NB (H2(p)) developed a highly variable disease course with symptoms originating from CNS above the spinal chord. C3H.Q lacks functional H2-E molecules and share H2-Aalpha with C3H.NB. To examine if the differences found at positions 85, 86, 88, and 89 in the Abeta-chains account for disease susceptibility, H2(q) mice were made transgenic with the Ab(p) gene. The Ab(p)-transgenic mice on the C3H.Q background developed a more severe disease course, demonstrating the importance of class II. However, the onset was not affected and the disease showed a classical ascending paralysis similar to the C3H.Q suggesting that the observed brain symptoms were related to nonclass II genes. Inhibition studies performed on affinity purified MHC class II molecules indicated that the PLP 103-116 peptide bound to A(p) with slightly higher affinity than to A(q). Both A(q) and A(p) formed long-lived stable complexes (t(1/2)>24 h) with the PLP 103-116 peptide, but a higher amount of the peptide was loaded on to A(p) compared with A(q). An F2 gene segregation experiment, in which the low PLP 103-116 binding A(r) molecule and the high binding A(p) molecule could be compared for the influence on the disease susceptibility, indicated a role for both peptide binding affinity and non-MHC genes. Based on our results, we conclude that the H2-Ab gene controls severity of EAE but not necessarily the onset or type of disease course and that affinity of the disease-promoting peptide for the class II molecule is a critical pathogenic factor.

Animals↗

PubMed2001

Microcirculation of human pancreatic islets transplanted under the renal capsule of nude mice.

BACKGROUND: The aim was to measure the capillary blood pressure in transplanted human islets. METHODS: Human islets were isolated at the Central Unit of the beta-cell Transplant in Brussels, Belgium. After transport to our laboratory, the islets were implanted under the renal capsule of normoglycemic nude mice. Two weeks later the capillary and venous blood pressures in the islet graft and adjacent renal parenchyma were measured with a micropuncture technique. RESULTS: Capillary blood pressure was approximately 5-8 mmHg in both graft and renal capillaries: twice as high as in native islets. Venous blood pressures were similar (4-5 mmHg) in the veins draining the graft and in the renal interlobular veins. All veins leading from the graft emptied into the renal parenchyma, that is, into interlobular veins. CONCLUSIONS: The capillary hypertension seen in transplanted human islets is probably necessary to secure adequate drainage through the renal veins. Whether this contributes to the poor results of long-term islet graft survival is unknown.

Adolescent↗

PubMed2001

Interaction of metals and thiols in cell damage and glutathione distribution: potentiation of mercury toxicity by dithiothreitol.

In the present study, we have investigated the effects of extracellular redox status and metal/thiol interactions on glutathione distribution in HeLa cell cultures. No effects were seen on glutathione distribution after the addition of different thiols, whereas the pro-oxidant copper ions affected glutathione distribution in several ways. The addition of dithiothreitol (DTT) but not the other thiols potentiated the effects of mercury ions on glutathione distribution and cell toxicity. In the presence of DTT, increased intra- and extracellular glutathione concentrations were noted already at 0.05 micromol/l, which was below the previously reported toxicity threshold for mercury ions in blood. Likewise DTT potentiated the effects of copper ions on glutathione distribution and cell toxicity, whereas the addition of DTT to cell cultures with a non-metal thiol reactive agent (hydroquinone) or an oxidative agent (hydrogen peroxide) did not affect glutathione distribution or cell toxicity. Thus, it seems as the synergistic effects between DTT and thiol reactive agents only apply to metal ions.

Acetylcysteine↗

PubMed2001

Epidemiology of HIV in Estonia.

The aim of this study was to report on the epidemiology of HIV infection in Estonia and to molecularly characterize Estonian HIV-1 variants. Epidemiological data were obtained from the Estonian National HIV/AIDS Database. In 1995-1996 blood samples were collected from 54 of the 65 HIV-infected individuals that had been diagnosed at that time. The V3 domain of the env gene was directly sequenced from peripheral blood mononuclear cells of 49 of these 54 individuals and the sequences used for phylogenetic analyses. At the end of 1999 Estonia reported 96 diagnosed HIV cases; 46 (48%) were homosexual or bisexual men and 31 (32%) were presumed to have been infected heterosexually. Importantly, only four individuals were likely to have become infected through intravenous drug use. Forty-three individuals (45%) were presumed to have been infected outside of Estonia, whereas 38 (40%) were likely to have become infected in Estonia. As expected, a majority of the investigated individuals (80%) were found to carry subtype B virus. Infections with subtypes A, C, D, G, and CRF02_AG were also documented. The dominance of subtype B was restricted to homosexual and bisexual men. Thus, subtype B infections were documented in 33 of 34 (97%) homosexual and bisexual men, but only 6 of 15 (40%) individuals with other probable routes of infection. Thirty of the 39 subtype B sequences were joined in a tight sequence cluster that also included sequences from neighboring Russia and Lithuania. This pattern suggests a local spread of HIV-1 among homosexual and bisexual men within the region. The results from the phylogenetic analyses agreed well with other epidemiological information. In conclusion, Estonia remains a country with a low prevalence of HIV infection. A majority of the identified cases are homosexual or bisexual men, whereas HIV infection among intravenous drug users is rare. A large proportion of the homosexual and bisexual men carried closely related subtype B variants. The sequences have been deposited in GenBank under accession numbers AF286538-AF286586.

Adolescent↗

PubMed2001

Species differences in susceptibility of transplanted and cultured pancreatic islets to the beta-cell toxin alloxan.

The beta-cell toxin alloxan, which produces oxygen radicals, is a model substance in studies of type 1 diabetes. Recently, human beta-cells have been found to be relatively resistant to this toxin. To clarify species differences in alloxan diabetogenicity, and oxygen radical toxicity, mouse, rat, rabbit, dog, pig, human and guinea pig islets have been studied after alloxan exposure. Using a standardized in vivo model, where islets were transplanted to nude mice, the different islets were compared. The results demonstrated that mouse and rat islet grafts were morphologically disturbed by alloxan and ROS. Rabbit and dog islet graft morphology was reasonably intact; and human, porcine, and guinea pig islet grafts were all well preserved. Furthermore, ultrastructural signs of apoptosis and necrosis, disturbances in the insulin secretory pattern during and after an alloxan perifusion, and islet lysosomal enzyme activities were studied in vitro in islets from some species. Guinea pig beta-cells were affected by alloxan, but a regeneration process compensated for the observed apoptotic and necrotic cell death. Human islets did not show any signs of alloxan-induced damage in the different models studied. Finally, no correlation between high alloxan sensitivity and high lysosomal enzyme activity was found. Thus, the beta-cell lysosomes are hardly specific targets for alloxan.

Adolescent↗

PubMed2001

The role of glycosaminoglycan binding of staphylococci in attachment to eukaryotic host cells.

Attachment of microorganisms to host cells is believed to be a critical early step in microbial pathogenesis. The aim of the study was to determine the role of the known glycosaminoglycan (GAG) binding activity of Staphylococcus aureus and coagulase-negative staphylococci (CoNS) in their attachment to six different eukaryotic cell lines. Three staphylococcal species expressing GAG binding capacity-S. aureus, S. epidermidis, and S. hemolyticus-were chosen for investigation. Six different eukaryotic cell lines, endothelial HUVEC and EA. hy 926 cells, epithelial A549 and HeLa S3 cells, fibroblasts HEL Sp 12 and macrophages J774.A1, were included. A modified ELISA with biotinylated bacteria was used for estimating the adhesion of staphylococci to each of the cell lines. Our results showed that staphylococci adhered to each of the cell lines studied, although the binding of CoNS strains to epithelial cells was lower than to the other cells. The attachment to all cell types could be partially decreased by pretreatment of the bacteria with various polysulfated agents (highest inhibition was 60%), as well as by chlorate and heparitinase treatment of the cells. These observations may suggest that at least one mode of staphylococcal attachment utilizes GAG chains present on the surface of virtually all adherent cells.

Animals↗

PubMed2001

Impact of temperature on nitrification in biological activated carbon (BAC) filters used for drinking water treatment.

The impact of temperature on nitrification in biological granular activated carbon (GAC) filters was evaluated in order to improve the understanding of the nitrification process in drinking water treatment. The study was conducted in a northern climate where very cold water temperatures (below 2 degrees C) prevail for extended periods and rapid shifts of temperature are frequent in the spring and fall. Ammonia removals were monitored and the fixed nitrifying biomass was measured using a method of potential nitrifying activity. The impact of temperature was evaluated on two different filter media: an opened superstructure wood-based activated carbon and a closed superstructure activated carbon-based on bituminous coal. The study was conducted at two levels: pilot scale (first-stage filters) and full-scale (second-stage filters) and the results indicate a strong temperature impact on nitrification activity. Ammonia removal capacities ranged from 40 to 90% in pilot filters, at temperatures above 10 degrees C, while more than 90% ammonia was removed in the full-scale filters for the same temperature range. At moderate temperatures (4-10 degrees C), the first stage pilot filters removed 10-40% of incoming ammonia for both media (opened and closed superstructure). In the full-scale filters, a difference between the two media in nitrification performances was observed at moderate temperatures: the ammonia removal rate in the opened superstructure support (more than 90%) was higher than in the closed superstructure support (45%). At low temperatures (below 4 degrees C) both media performed poorly. Ammonia removal capacities were below 30% in both pilot- and full-scale filters.

Ammonia↗

PubMed2001

Paired multiplex reverse-transcriptase polymerase chain reaction (PMRT-PCR) analysis as a rapid and accurate diagnostic tool for the detection of MLL fusion genes in hematologic malignancies.

The MLL gene in chromosome band 11q23 is frequently rearranged in acute lymphoblastic and acute myeloid leukemias. To date, more than 50 different chromosomal regions are known to participate in translocations involving 11q23, many of which affect MLL. The pathogenetically important outcome of these rearrangements is most likely the creation of a fusion gene consisting of the 5' part of the MLL gene and the 3' end of the partner gene. Although abnormalities of the MLL gene as such are generally associated with poor survival, recent data suggest that the prognostic impact varies among the different fusion genes generated. Hence, detection of the specific chimeric gene produced is important for proper prognostication and clinical decision making. We have developed a paired multiplex reverse-transcriptase polymerase chain reaction analysis to facilitate a rapid and accurate detection of the most frequent MLL fusion genes in adult and childhood acute leukemias. To increase the specificity, two sets of primers were designed for each fusion gene, and these paired primer sets were run in parallel in two separate multiplex one-step PCR reactions. Using the described protocol, we were able to amplify successfully, in one single assay, the six clinically relevant fusion genes generated by the t(4;11)(q21;q23) [MLL/AF4], t(6;11)(q27;q23) [MLL/AF6], t(9;11)(p21-22;q23) [MLL/AF9], t(10;11)(p11-13;q23) [MLL/AF10], t(11;19)(q23;p13.1) [MLL/ELL], and t(11;19)(q23; p13.3) [MLL/ENL] in cell lines, as well as in patient material.

Biomarkers, Tumor↗

PubMed2001

Cardiac natriuretic peptides and pancreatic islet blood flow in anesthetized rats.

The aim of the study was to evaluate effects of cardiac natriuretic peptides on splanchnic circulation, especially to the pancreatic islets. Pentobarbital-anesthetized rats were infused intravenously (0.01 ml/min for 20 min) with saline, atrial natriuretic peptide (ANP; 0.25 or 0.5 microg/kg BW/min), brain natriuretic peptide (BNP; 0.5 microg/kg BW/min) or C-type natriuretic peptide (CNP; 0.5 or 2.0 microg/kg BW/min). Splanchnic blood perfusion was then measured with a microsphere technique. Mean arterial blood pressure was decreased by ANP and BNP, but not by CNP. The animals given the highest dose of ANP became markedly hypoglycemic, whilst no such effects were seen in any of the other groups of animals. Total pancreatic blood flow was decreased by the highest dose of CNP, whereas no change was seen after administration of the other peptides. Islet blood flow was increased by the highest dose of ANP. Neither BNP nor CNP affected islet blood flow. None of the natriuretic peptides influenced duodenal, colonic or arterial hepatic blood flow. It is concluded that cardiac natriuretic peptides exert only minor effects on splanchnic blood perfusion in anesthetized rats. However, islet blood perfusion may be influenced by ANP.

Animals↗

PubMed2001

Capillary blood pressure in the endocrine and exocrine parenchyma of rat pancreas transplants.

BACKGROUND: Transplantation of isolated organs or cells leads to a functional denervation of the organ, which may cause a hyperperfusion of blood. The current study evaluated to what extent blood perfusion and capillary blood pressures were affected in the transplanted rat pancreas. METHODS: Inbred, male Wistar-Furth rats underwent transplantation with a syngeneic pancreaticoduodenal graft. Four weeks later, blood flow to the native and transplanted pancreases was measured with a microsphere technique. Capillary pressures were measured by direct micropuncture technique. RESULTS: An increased islet blood flow was consistently observed in the transplanted pancreas as compared with the native organ, while whole pancreatic and duodenal blood flow was similar in the native and transplanted organs. The capillary pressure was twice as high in the exocrine pancreas (6-7 mm Hg) of both the native and transplanted glands when compared with that of the islets (approximately 3 mm Hg). There were no differences in the capillary pressures in either the islets or exocrine gland when native and transplanted pancreases were compared. CONCLUSIONS: We conclude that the transplanted whole pancreas retains a low islet capillary blood pressure after transplantation despite having a higher islet blood perfusion.

Animals↗

PubMed2001

Polyamines in pancreatic islets of obese-hyperglycemic (ob/ob) mice of different ages.

To further evaluate the role of polyamines in insulin production and cell replication in diabetic pancreatic islets, we have studied hyperplastic islets of obese-hyperglycemic mice of different ages and normal islets of the same strain. The aims of the study were to investigate the impact of the diabetic state and aging on polyamine contents and requirements in these islets. Cultured islets from lean and obese animals contained significantly less polyamines than freshly isolated islets. Spermine-to-spermidine ratio was elevated in freshly isolated islets from young obese mice compared with those from lean mice. In islets from old obese animals, spermidine content was decreased, whereas the content of spermine was not different from that of young obese mice. The physiological significance of polyamines was investigated by exposing islets in tissue culture to inhibitors of polyamine synthesis. This treatment caused a partial polyamine depletion in whole islets but failed to affect polyamine content of cell nuclei. Insulin content was not affected in polyamine-deficient islets of obese mice, irrespective of age, in contrast to decreased islet insulin content in polyamine-depleted young lean animals. Polyamine depletion depressed DNA synthesis rate in obese mouse islets; in lean mice it actually stimulated DNA synthesis. We concluded that important qualitative and quantitative differences exist between islets from obese-hyperglycemic and normal mice with respect to polyamine content and requirements of polyamines for regulation of insulin content and cell proliferation. The results suggest that spermine may be involved in mediating the rapid islet cell proliferation noted early in obese-hyperglycemic syndrome, but changes in spermine concentration do not seem to account for the decline in islet cell DNA synthesis in aged normoglycemic animals.

Age Factors↗

PubMed2001

Hyperhomocysteinemia and changed plasma thiol redox status in chronic obstructive pulmonary disease.

Reduced and total homocysteine, cysteine, glutathione and cysteinylglycine in plasma were investigated in 19 patients with chronic obstructive pulmonary disease and in 29 healthy subjects. The purpose was to examine the influence of pro-oxidant activity caused by the lung disease on the metabolism of homocysteine and other plasma thiols. We observed a decreased concentration of reduced glutathione and a decreased ratio of reduced/total glutathione in the patients compared to the healthy individuals, which supports the hypothesis of an association between free radicals and pathogenesis in some lung diseases. We also observed an increased total plasma homocysteine. The influence of a possible extracellular pro-oxidant activity on the concentration of total plasma homocysteine is discussed.

Aged↗

PubMed2001

Stimulated endocrine cell proliferation and differentiation in transplanted human pancreatic islets: effects of the ob gene and compensatory growth of the implantation organ.

Neogenesis is crucial for the maintenance of beta-cell mass in the human pancreas and possibly for the outcome of clinical islet transplantation. To date, no studies have reported a stimulation of human beta-cell neogenesis in vivo. Therefore, we investigated whether human alpha-, beta-, and duct cell growth can be stimulated when human islets are xenotransplanted to obese hyperglycemic-hyperinsulinemic ob/ob mice immunosuppressed with anti-lymphocyte serum. Moreover, we wanted to study whether beta-cell growth and duct-to-beta-cell differentiation were induced in the hepatocyte growth factor (HGF)-dependent compensatory kidney growth model. For that purpose, we evaluated human islets grafted to nude (nu/nu) mice before uninephrectomy of the contralateral kidney for DNA-synthesis and duct cell expression of the beta-cell-specific transcription factor Nkx 6.1 as an estimate of differentiation. Human islet grafts were well preserved after 2 weeks when transplanted to ob/ob mice during anti-lymphocyte immunosuppression. Both human beta-cells (P < 0.01) and duct cells (P < 0.001) were growth stimulated when islets were transplanted to ob/ob mice. We also observed a correlation between increased duct cell proliferation and increased organ donor age (P = 0.02). Moreover, duct (P < 0.05) and beta-cell (P < 0.05) proliferation, as well as duct cell Nkx 6.1 expression (P < 0.05), were enhanced by the compensatory kidney growth after uninephrectomy. We conclude that it is possible to stimulate human beta-cell neogenesis in vivo, provided that the recipient carries certain growth-stimulatory traits. Furthermore, it seems that duct cell proliferation increases with increasing organ donor age. Altogether, these data and previous results from our laboratory suggest that human beta-cell neogenesis becomes more dependent on differentiation and less dependent on proliferation with increasing age.

Adaptation, Physiological↗

PubMed2001

Markedly decreased oxygen tension in transplanted rat pancreatic islets irrespective of the implantation site.

In this study, we syngeneically transplanted islets to three different implantation sites of diabetic and nondiabetic rats, then 9-12 weeks later we measured the blood perfusion and compared the tissue partial pressure of oxygen (PO2) levels of these transplanted islets to endogenous islets. Modified Clark microelectrodes (outer tip diameter 2-6 microm) were used for the oxygen tension measurements, and islet transplant blood perfusion was recorded by laser-Doppler flowmetry (probe diameter 0.45 mm). The islet graft blood perfusion was similar in all islet grafts, irrespective of the implantation site. In comparison, the three implantation organs (the kidney cortex, liver, and spleen) differed markedly in their blood perfusion. There were no differences in islet graft blood perfusion between diabetic and nondiabetic recipients. Within native pancreatic islets, the mean PO2 was approximately 40 mmHg; however, all transplanted islets had a mean PO2 of approximately 5 mmHg. The oxygen tension of the grafts did not differ among the implantation sites. In diabetic recipients, an even lower PO2 level was recorded in the islet transplants. We conclude that the choice of implantation site seems less important than intrinsic properties of the transplanted islets with regard to the degree of revascularization and concomitant blood perfusion. Furthermore, the mean PO2 level in islets implanted to the kidney, liver, and spleen was markedly decreased at all three implantation sites when compared with native islets, especially in diabetic recipients. These results are suggestive of an insufficient oxygenization of revascularized transplanted islets, irrespective of the implantation site.

Animals↗

PubMed2001

Trophic transfer and passive uptake of a polychlorinated biphenyl in experimental marine microbial communities.

To study the uptake mechanisms of 2,2',4,4',6,6'-hexachlorobiphenyl (HxCB 153) in microplankton with different feeding strategies, two laboratory communities were used. Trophic transfer of HxCB 153 was tested in a heterotrophic microbial food web consisting of bacteria, flagellates, and ciliates. Passive uptake was tested in a community consisting of algae and bacteria. The experiments were conducted over 6 d, and samples were retrieved daily. In the heterotrophic food web, a significant increase of the HxCB 153 concentration was observed in the top predator level (ciliates, p < 0.05), where the concentration doubled during the 3 d of the experiment. A concomitant decrease was observed in the ciliate prey (flagellates), indicating that HxCB 153 was redistributed due to trophic transfer. On average, 33% of the HxCB 153 was sorbed to ciliates over the course of the experiment. In the experiment with algae and bacteria, the HxCB 153 concentrations were relatively stable over time. The largest fraction partitioned into bacteria (57%), whereas only 4% of the HxCB 153 sorbed to the algae. The uptake was 8-fold higher in ciliates than in algae, although the algal biomass was 10-fold higher. The results imply that trophic transfer may be a significant transport route of more hydrophobic organic contaminants (HOCs) in plankton communities. In transfer models, this pathway may be taken into consideration so that the transport rate of HOCs to higher trophic levels is not underestimated.

Absorption↗