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Biomedical subjects

G Andersson

Publications and source records attributed to G Andersson.

At least 217 records · Page 12Linked to original sources
PubMed1990

Effect of phenytoin medication on the metabolism of epidermal growth factor receptor in cultured gingival fibroblasts.

Human gingival fibroblasts derived from 2 patients before and 9 months after the start of phenytoin (PHT) therapy were studied with respect to the effect of epidermal growth factor (EGF) on the incorporation of 3H-thymidine into DNA, binding of EGF to its cell-surface receptor, internalization of EGF-receptor-ligand complexes and, finally, with respect to EGF receptor mRNA levels. In fibroblasts derived from the patient who developed gingival overgrowth during the PHT medication (responder) as well as in the fibroblasts derived from the patient where gingival overgrowth did not develop (non-responder), the affinity of the EGF receptor for EGF was not significantly changed. In the non-responder patient the internalization of EGF receptor ligand was decreased, whereas it was increased in the fibroblasts derived from the responder patient after PHT therapy. The steady-state level of EGF-r mRNA increased significantly (p less than 0.001) in the cultured fibroblasts derived from the non-responder but decreased (p less than 0.05) in the responder patient following PHT therapy. Ligand affinity cross-linking studies revealed one major component of EGF receptor with a molecular weight of 170 KDa in fibroblasts from the non-responder as well as from the responder. The study indicates that PHT medication results in a down-regulation of EGF receptor metabolism in fibroblasts derived from a responder patient, whereas in the non-responder patient EGF receptor metabolism is up-regulated.

Cell Division↗
PubMed1990

Amperozide--effect on prolactin release in the rat.

Amperozide, a new putatively antipsychotic drug was investigated for its effect on prolactin release in the rat. A significant decrease in the plasma concentration of prolactin was found at 30 minutes after treatment with amperozide. However, there was no effect of amperozide on prolactin release from isolated pituitary cells. These results suggest that there is no direct effect of amperozide on the pituitary lactotrophs and that the attenuation of prolactin secretion in vivo is mediated at a higher level.

Animals↗
PubMed1990

Number of cells from Plasmodium falciparum-immune donors that produce gamma interferon in vitro in response to Pf155/RESA, a malaria vaccine candidate antigen.

Secretion of gamma interferon (IFN-gamma) in response to stimulation of Plasmodium falciparum-primed T cells by specific antigens may be a useful indicator of cellular immunity to malaria. An enzyme-linked immunospot (ELISPOT) assay designed to detect IFN-gamma at the single-cell level was used to study IFN-gamma-producing cells from P. falciparum-primed donors from The Gambia after in vitro stimulation with various malarial antigens. IFN-gamma secreted into the culture supernatant was measured by conventional enzyme-linked immunosorbent assay (ELISA). There was a good correlation in individual donors between the level of IFN-gamma secreted into the culture supernatant and the number of IFN-gamma-secreting cells. However, the ELISPOT assay was apparently more sensitive in demonstrating low levels of IFN-gamma production than the ELISA was. Thus after stimulation with crude P. falciparum antigen from infected erythrocytes, 72% of the primed donors responded positively in the ELISPOT assay but only 55% responded positively in the ELISA. When stimulated with synthetic peptides representing immunodominant epitopes of the malarial antigen Pf155/RESA, a vaccine candidate, 31 to 55% responded in the ELISPOT assay and 21 to 36% responded in the ELISA. Unprimed Europeans did not respond positively to these antigens in either of the assays, and background in antigen-free controls was generally low. These results indicate that measurement of IFN-gamma by the ELISPOT assay or ELISA should have wide applications in large-scale epidemiological studies of malaria immunity. In addition, the ELISPOT assay makes it possible to analyze the T cells responding to malarial antigens in terms of both numbers and functional heterogeneity.

Adult↗
PubMed1990

Effect of amperozide on the dopamine synthesis activity in the tuberoinfundibular neurons.

The ability of amperozide (N-ethyl-4-[4,4-bis(p-fluorophenyl)butyl]-1-piperazinecarboxamide) , a potentially antipsychotic agent, to activate the tuberoinfundibular dopamine (TIDA) neurons was studied by measuring the accumulation of dihydroxyphenylalanine (DOPA) in the median eminence after inhibition of DOPA decarboxylase. The activity of the TIDA neurons was markedly elevated in a dose-related manner after treatment with amperozide (1 and 10 mg/kg). A significant stimulation was also found following treatment with the atypical antipsychotic agent clozapine (20 mg/kg) while the typical antipsychotic drug haloperiodol had no effect on TIDA neuron activity. The stimulatory effect of amperiozide on the TIDA neurons is suggested to be mediated by a non-dopaminergic mechanism.

Animals↗
PubMed1989

Monoclonal antibody two-site ELISA for human IFN-gamma. Adaptation for determinations in human serum or plasma.

Mouse monoclonal antibodies (mAbs) against human interferon-gamma (IFN-gamma) were produced after immunization with recombinant IFN-gamma. Two mAbs (1-D1K and 7-B6-1) recognizing distinct epitopes on natural IFN-gamma were selected for the development of a two-site ELISA. The sensitivity was similar for IFN-gamma diluted in PBS with 1% bovine albumin, spent culture medium or fetal calf serum but reduced to approximately 50% when diluted in normal human serum. Individual normal human sera were tested and three of 14 gave false reactivities in the ELISA. One serum factor with major impact on the individual variation and the decreased sensitivity could be adsorbed to and eluted from protein A-Sepharose. Based on these observations we established a new ELISA protocol which made it possible to test for low levels of IFN-gamma in human serum and plasma samples. The modifications in this protocol are easy to apply with basic laboratory equipment.

Antibodies, Monoclonal↗
PubMed1989

T and B cell responses of Plasmodium falciparum malaria-immune individuals to synthetic peptides corresponding to sequences in different regions of the P. falciparum antigen Pf155/RESA.

The C-terminal (3') amino acid repeat region of the Plasmodium falciparum Ag Pf155/RESA, a vaccine candidate, contains immunodominant T and B cell epitopes. In order to identify additional T cell epitopes in the molecule, synthetic peptides corresponding to the centrally (5') located repeat region, as well as to four nonrepeated regions, were synthesized. T cells from 46 P. falciparum-primed individuals living in a holoendemic area of The Gambia where malaria transmission is seasonal were tested for their responsiveness to the peptides by thymidine incorporation and IFN-gamma release. There was a considerable variation in the response to different peptides. Proliferation and IFN-gamma release were not correlated in individual donors, underlining the importance of measuring both activities when screening donor populations for total T cell responsiveness to a given Ag. Whereas 72% of the donors responded with proliferation and/or IFN-gamma release to the intact protein the mean % responders to the peptides was 40%. The most frequent responses (up to 60%) were induced with peptides from the 3'- and 5'-repeat region of the protein. Analysis of some closely related sequences in the 3'-repeat region indicated that they contained at least two epitopes that were either distinct or cross-reacting in different donors, suggesting difference in the genetic control of these responses. When the same peptides were investigated for reactivity with antibodies, the best T cell inducing sequences also displayed the best antibody reactivities. However, in individual donors, T and B cell responses were not correlated. T cell responses were shown to persist after a period with no P. falciparum transmission, whereas antibody concentrations tended to decrease, suggesting differences in the requirements of boosting at the T and B cell levels, respectively.

Amino Acid Sequence↗
PubMed1989

Characterization of hepatic lactogen receptor. Subcellular distribution and characterization of N-linked carbohydrate chains.

The types of carbohydrate chains present in a rat liver lactogenic hormone-binding receptor species with an Mr of 82,000, and in its hormone-binding subunits with Mr values of 40,000 and 35,000, were characterized using carbohydrate-chain-cleaving enzymes and affinity cross-linking. The subcellular distribution of lactogenic hormone-binding species was studied in organelle-enriched fractions. The monomeric Mr-40,000 and Mr-35,000 species contain N-linked tri- or tetra-antennary complex and high-mannose chains respectively. The Mr-82,000 species exists in two forms, where the Mr-40,000 and Mr-35,000 subunits are each combined with unglycosylated and, with the technique used, unlabelled subunit(s). Studies with organelle-enriched fractions revealed that the Mr-35,000 species was found in an endoplasmic reticulum-enriched fraction. The Mr-40,000 species was the predominant monomeric binding species in Golgi/endosome- and plasma membrane-enriched fractions. It is suggested that the Mr-35,000 species is a precursor to the Mr-40,000 species. In lysosome/endosome- or lysosome-enriched fractions, a broad distribution in Mr (35,000-40,000) was characteristic of the hormone-binding species. The Mr-82,000 species was only found in a Golgi/endosome-enriched fraction. Labelling of endosome lactogen receptor by injection of 125I-labelled ovine prolactin in vivo and cross-linking yielded only the Mr-40,000 species. Thus, the Mr-40,000 and Mr-35,000 lactogenic hormone-binding species each appear to be combined with the unglycosylated receptor subunit(s) in the Golgi complex to form Mr-82,000 heterodimeric complexes.

Animals↗
PubMed1989

Biogenesis of the somatogenic receptor in rat liver.

Certain structural characteristics, in particular the type of oligosaccharide chains associated with the rat liver somatogenic (GH) receptors, were studied in different isolated organelles involved in receptor biosynthesis, maturation, and binding, with the use of ligand-affinity cross-linking, incubation with various oligosaccharide chain-cleaving enzymes, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In an endoplasmic reticulum-enriched fraction, a somatogenic receptor with Mr 33,000, after correction for bound ligand (assuming a 1:1 binding ratio of ligand to receptor) was found to contain N-linked high mannose oligosaccharide chain(s). In an intermediate density fraction, enriched in cis-Golgi, a major receptor of Mr 43,000 was found to contain N-linked complex type of oligosaccharide chains. In a low density membrane fraction, containing trans-Golgi complex membranes and endocytic vesicles, three receptors of Mr 95,000, 55,000, and 43,000 were found. These three receptors contain N-linked complex-type oligosaccharide chains. Neuraminidase treatment resulted in a decrease of the Mr 95,000 and 43,000 receptors to Mr 81,000 and 39,000, respectively. Two specific somatogenic receptors of Mr 95,000 and 43,000 containing N-linked complex type of oligosaccharides were found in an isolated plasma membrane-enriched fraction. When isolated hepatocytes were analyzed, the Mr 95,000 receptor was found to be the major labeled species. Two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis (first dimension nonreducing and the second dimension reducing conditions), showed that the Mr 43,000 receptor is contained within the Mr 95,000 receptor. The data suggest that the Mr 33,000 receptor found in endoplasmic reticulum constitutes a precursor to the Mr 43,000 receptor and that the Mr 43,000 receptor is complexed with an unknown subunit during transport through the Golgi complex to form an Mr 95,000 receptor present on the cell surface.

Animals↗
PubMed1989

Female choice selects for a viability-based male trait in pheasants.

Recent theory on sexual selection suggests that females in species without paternal care choose mates by their secondary sexual characters because these indicate genotypic quality which will be transmitted to the offspring. These ideas are not yet empirically supported as data quantifying the relationship between female mate choice and female reproductive success are lacking. Only in one case, in Colias butterflies, has it been demonstrated unequivocally that females choose 'good genotypes' as mates and there is only one study, on Drosophila, demonstrating that mate choice increases one component of offspring fitness. Spur length of male pheasants (Phasianus colchicus) correlates with various fitness-related properties. We here present the first experimental field data showing that female pheasants select mates on the basis of male spur length and that female mate choice correlates with female reproductive success.

Animals↗
PubMed1989

Regression of left ventricular hypertrophy on long-term treatment with captopril of severe hypertensives refractory to standard triple treatment.

Ten patients (mean age 53 years; range 37-65 years) with hypertension refractory to standard triple treatment were selected for measurement of blood pressure and echocardiographic evaluation of the left ventricular dimensions before and after 3, 6 and 12 months of captopril therapy. In each patient the dose of captopril was titrated to a maximum of 150 mg t.d.s. (range 25 to 150 mg t.d.s.) with a therapeutic goal of less than or equal to 90 mm Hg diastolic blood pressure. Most patients had added diuretic therapy. Four patients were unable to complete the study, two because of insufficient response to captopril therapy, and two because of side-effects (skin rash and cough). A significant fall in blood pressure was seen after three months of treatment and a reduced blood pressure was still maintained after 12 months. Over the same period, the average number of drugs was reduced from 3.6 to 2.1 per patient. A gradual reduction of septal and posterior wall thickness were noted, from 12.8 and 11.5 mm to 10.0 and 8.5 mm, respectively, after 12 months. Calculated left ventricular muscle mass was insignificantly reduced from 281 to 243 g after 12 months. The present study suggests that in hypertension resistant to conventional multiple therapy, captopril can reduce the blood pressure, and, in the long run it can also induce reversal of left ventricular wall thickening without causing deterioration of left ventricular function.

Adult↗
PubMed1989

Interferon-alpha: a gene family in therapeutic use.

Several variants of interferon-alpha (IFN-alpha) were isolated and purified to homogeneity. They differed to various degrees in biological properties. However, three IFN-alpha 2 variants showed only minor differences from a variant called IFN-alpha 88 with regard to their ability to inhibit growth and to bind to specific receptors, tested on Daudi cells. Two monoclonal antibodies were studied, which showed overlapping specificity for at least one peptide obtained after HPLC separation of tryptic digests. The monoclonal antibodies could discriminate between sequence differences to a much higher degree than the receptor on Daudi cells. It is concluded that the receptor is degenerate and binds well to different structural variants of IFN and that for therapeutic use, several of the variants will probably have the same biological potency.

Antibodies, Monoclonal↗
PubMed1989

Wasting pig syndrome (WPS) in weaners--treatment with amperozide.

Social and environmental stressors during the critical period of weaning frequently affect not only performance but also the health status of piglets. Pigs unable to cope with the changes associated with weaning develop a condition characterized by slowing of growth and a listless or unthrifty appearance, known as the wasting pig syndrome (WPS). In the present investigation a total of 100 4-week-old wasting pigs were studied. The pigs were divided randomly into 10 pens (10 animals per pen). Half the number of pigs were treated orally with amperozide (2.5 mg/kg body-weight), a psychotropic drug shown to modify emotional behaviour in response to social stress. Control groups were treated with long-acting oxytetracycline and vitamins (A + D3 + E). There were significant improvements in average daily weight gain (P less than 0.05) and feed conversion ratio (P less than 0.01) in amperozide-treated pigs compared with controls. Furthermore, there was a significant reduction (P less than 0.05) in mortality in amperozide treated groups. Within 2 weeks following amperozide treatment the clinical signs of the WPS had disappeared and the pigs grew at the same rate as normal healthy pigs.

Animals↗
PubMed1989

Clinical appearance of lesions associated with the use of loose and portion-bag packed Swedish moist snuff: a comparative study.

The aim of this study was to register and compare clinical oral mucosal lesions and gingival recessions associated with the use of two different smokeless tobacco products, loose snuff and portion-bag packed snuff. Selected for the study were 252 men (mean age 36.3 yr) of whom 184 (mean age 36.0 yr) used exclusively loose snuff and 68 (mean age 36.9 yr) exclusively portion-bag snuff. Oral mucosal lesions were registered according to a four-grade clinical scale. There was a significantly larger proportion of less pronounced lesions, Degrees 1 and 2, among the users of portion-bag snuff compared with the users of loose snuff. This was also valid when differences in consumption data were considered. Smokeless tobacco-associated gingival recessions were found in 42 (23.5%) subjects among the users of loose snuff and in 2 (2.9%) subjects among the users of portion-bag snuff. The results of this study support previous preliminary assessments that clinical changes of the oral mucosa and the gingival margin are less pronounced among those who use portion-bag snuff than among those who use loose snuff.

Adolescent↗
PubMed1989

Histologic changes associated with the use of loose and portion-bag packed Swedish moist snuff: a comparative study.

This study was to identify histologic tissue changes in the oral mucosa and to compare them in specimens from users of loose can-packed and portion-bag-packed moist snuff. The material consisted of biopsies from 252 regular snuff users. 184 using exclusively loose and 68 portion-bag snuff. An array of structural changes appearing in different combinations were identified among the 252 specimens. Two major patterns were recognized based on changes in the surface layer. Type 1 was characterized by an increased epithelial thickness with vacuolated cells and frequent chevron type changes. Type 2 showed a variably thickened surface layer with evidence of keratinization. Based on these findings, 14 carefully matched pairs of loose and portion-bag users were analyzed and compared. Loose snuff users showed predominantly histologic Type 1 changes while portion-bag users showed more histologic Type 2 or only very discrete changes.

Adult↗
PubMed1989

Thyroid hormone and not growth hormone is the principle regulator of mammalian mitochondrial biogenesis.

T3 and GH have been implicated in the regulation of mitochondrial biogenesis. Since thyroid hormone promotes the synthesis of growth hormone, its control of human mitochondrial biogenesis could arise through a permissive action on GH biosynthesis. This was studied in hypophysectomized rats treated with T3 and/or human GH by the continuous infusion of hormone for 6 days from mini-infusion pumps implanted sc. Increases in mitochondrial respiration, enzyme activities, and protein synthesis were found in isolated liver mitochondria from rats receiving T3. In contrast, GH alone had no effect, nor did it increase the response to T3. Since it has been argued that mitochondrial biogenesis results from a direct interaction (binding) of GH with mitochondria, GH-specific binding sites were measured with 125I-bGH, a specific somatogenic receptor ligand, in isolated mitochondrial membranes in vitro. In addition, the intracellular endocytic uptake of 125I-bGH injected in vivo was compared in purified subcellular membrane fractions and mitochondria. No evidence in favour of specific GH interaction on mitochondrial membranes was found by either test. It is concluded that T3 exerts a direct, rather than permissive, effect on mitochondrial biogenesis, and that high affinity binding sites for GH are not present in rat liver mitochondria.

Animals↗
PubMed1989

Growth hormone regulates the rodent hepatic epidermal growth factor receptor at a pretranslational level.

Recent studies have implicated the involvement of pituitary factor(s) in the regulation of hepatic epidermal growth factor receptor (EGF-R) levels. In the present study the possible role of GH as a regulator of EGF-R has been examined by measuring hepatic EGF-R mRNA and EGF binding in intact and GH-deficient rats and mice before and after administration of GH. Using a human EGF-R probe, 10.5 and 6.0 kb transcripts were detected in mouse and rat liver by Northern gel analysis. EGF-R mRNA was quantified by solution hybridization, and EGF binding determined by incubation of 125I-labelled EGF with a low-density membrane fraction. Levels of hepatic EGF-R mRNA and binding of EGF in female rats were about two-thirds of those in male rats. GH-deficient (lit/lit) male and female mice had approximately 10 and 25% respectively of the levels of EGF-R mRNA and EGF binding of intact male and female mice. Furthermore, hypophysectomized rats exhibited a reduced level of EGF-R mRNA and EGF binding, corresponding to about 20% of the levels detected in intact male rats. When hypophysectomized male and female rats received recombinant human GH (hGH) either as intermittent injections or by continuous infusion using osmotic minipumps, the EGF-R mRNA and EGF binding levels increased to about half those of the intact male animals. No differences between intermittent or continuous administration of hGH on the induction of EGF-R mRNA or EGF binding could be seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Isolation and characterization of skeletal acid ATPase--a new osteoclast marker?

A tartrate-resistant, iron-activated and vanadate-sensitive nucleotide tri- and diphosphatase has been purified from rat bone. The purified enzyme (1,400-fold, 45% yield) has an Mr on SDS-PAGE of 30,000 Da. Hydrodynamic properties include a Stokes radius of 24A, a sedimentation coefficient of 3.2 S and a partial specific volume of 0.748 ml/g. The calculated Mr from hydrodynamic data is 32,000 and the enzyme binds 4 mol Triton X-100/mol enzyme. Substrate specificity studies demonstrate that the enzyme is active against nucleotide tri- and diphosphates and phosphotyrosine, but not against phosphoserine or phosphothreonine. Based on the purification profile and enzyme histochemistry, showing labelling of fewer mononuclear cells using ATP compared to conventional acid phosphatase substrates, it is suggested that the acid ATPase constitutes a unique form in the family of tartrate-resistant acid phosphatases and may thus have the potential as a marker for osteoclast ontogeny and function.

Acid Phosphatase↗