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Biomedical subjects

B Jansson

Publications and source records attributed to B Jansson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Morphological changes in rat submandibular gland mucous cells during fixation with 10% formalin.

The features of mucous cells in 10% formalin (FA)-fixed submandibular glands differ markedly from those fixed in glutaraldehyde (GA). We therefore studied morphological changes in mucous cells during 10% FA fixation. Mucous cells were fixed in either 10% FA, neutral sodium-phosphate-buffered (Na-PBed) 10% FA, ice-cold 10% FA or an ice-cold fixative mixture of 2.0% paraformaldehyde (PA) and 0.5% GA. Two different methods were used: immersion fixation and venous perfusion fixation. The 10% FA-fixed tissues had elliptical or flattened nuclei, a clear cytoplasm and no secretory granules. Tissues fixed with the fixative mixture displayed almost round nuclei, a broad endoplasmic reticulum and abundant secretory granules in the cytoplasm. Tissues immersion-fixed with neutral Na-PBed 10% FA or perfusion-fixed with ice-cold 10% FA had almost the same light microscopic appearance as that of the mixture-fixed tissues. To elucidate the process of morphological changes during 10% FA fixation at room temperature, samples immersed in 10% FA for varying periods of time were postfixed immediately in the fixative mixture and exposed to microwave irradiation. This method produced a variety of findings, even within the same section. There was a significant difference in the findings seen in the center of the section and at the periphery. The initial changes caused by 10% FA were rupture of the secretory granules located in the perinuclear region and destruction of the perinuclear organelles such as Golgi apparatus, mitochondria and endoplasmic reticulum. Absorption of the endoplasmic reticulum progressed so that the perinuclear region became translucent. To obtain a better structure in mucous cells from the fixed submandibular gland tissues, an appropriate fixative such as GA should be used and the fixative should infiltrate into the tissues as quickly as possible.

Animals↗
PubMed1996

An assessment of the systemic effects of single and repeated doses of inhaled fluticasone propionate and inhaled budesonide in healthy volunteers.

The systemic effects of single and multiple doses of inhaled fluticasone propionate (FP) and budesonide were examined in 24 healthy male volunteers (age range 18-29 years). The study was of an open, placebo-controlled, randomized, three-way crossover design. On each study day, multiple blood samples were taken over a 20 h period after drug administration (after a single dose and after the last of seven doses) and area under the curve (AUC(0-20)) for plasma cortisol and white blood cell (WBC) counts was calculated. RESULTS. The present study shows that multiple dosing with FP 1.0 mg b.i.d. for 3.5 days (seven doses) resulted in a marked cortisol suppression from placebo which, at 55%, was more than double that seen with a single dose (25% suppression). Multiple dosing with budesonide 0.8 mg b.i.d. resulted in a 34% suppression in plasma cortisol compared with a suppression of 26% with a single dose. The increase in systemic activity of FP after multiple dosing is confirmed by both the number of subjects with 0800 hours plasma cortisol values below normal limits and by the changes in WBC and differential counts. CONCLUSION. The results of the present study confirm previous findings with regard to the more marked systemic effect of FP following multiple dosing as compared with a single dose. This increase in systemic effect from single dosing to multiple dosing is significantly greater for FP than for budesonide.

Administration, Inhalation↗
PubMed1996

Sensitivity of HIV-1 to neutralization by antibodies against O-linked carbohydrate epitopes despite deletion of O-glycosylation signals in the V3 loop.

It has been suggested that threonine or serine residues in the V3 loop of HIV-1 gp120 are glycosylated with the short-chain O-linked oligosaccharides Tn or sialosyl-Tn that function as epitopes for broadly neutralizing carbohydrate specific antibodies. In this study we examined whether mutation of such threonine or serine residues could decrease the sensitivity to infectivity inhibition by Tn or sialosyl-Tn specific antibodies. All potentially O-glycosylated threonine and serine residues in the V3 loop of cloned HIV-1 BRU were mutagenized to alanine thus abrogating any O-glycosylation at these sites. Additionally, one of these T-A mutants (T308A) also abrogated the signal for N-glycosylation at N306 inside the V3-loop. The mutant clones were compared with the wild type virus as to sensitivity to neutralization with monoclonal and polyclonal antibodies specific for the tip of the V3 loop of BRU or for the O-linked oligosaccharides Tn or sialosyl-Tn. Deletion of the N-linked oligosaccharide at N306 increased the neutralization sensitivity to antibodies specific for the tip of the loop, which indicates that N-linked glycosylation modulates the accessibility to this immunodominant epitope. However, none of the mutants with deletions of O-glycosylation signals in the V3 loop displayed any decrease in sensitivity to anti-Tn or anti-sialosyl-Tn antibody. This indicates that these broadly specific neutralization epitopes are located outside the V3 loop of gp 120.

Amino Acid Sequence↗
PubMed1996

Defective threonine-linked glycosylation of human insulin-like growth factor in mutants of the yeast Saccharomyces cerevisiae.

Mutants of the yeast Saccharomyces cerevisiae were identified, in which O-glycosylation at threonine 29 of a heterologous protein, human insulin-like growth factor (hIGF-1), is defective. In mutant M195, O-glycosylation of hIGF-1, but not of yeast proteins chitinase and a-agglutinin, was reduced; in mutant M577 yeast proteins were affected besides hIGF-1. The mutations of M195 and M577 did not affect viability and could not be complemented by the PMT1 or PMT2 genes. The mutant phenotype of strain M195 was reconstituted in an in vitro system, in which a hIGF-1-derived peptide encompassing residues 24-34 was not used as acceptor for mannosylation, while unrelated peptides were glycosylated at wild-type levels. hIGF-1 glycosylation was drastically reduced in pmt1 disruptants and to a lesser extent in pmt2 disruptants, suggesting interaction between the PMT gene products and components mutated in M195 and M577 cells. The results suggest that mutations may only affect O-glycosylation of a specific subset of secreted proteins in yeast.

Amino Acid Sequence↗
PubMed1996

Rapid selection for an N-linked oligosaccharide by monoclonal antibodies directed against the V3 loop of human immunodeficiency virus type 1.

The V3 loop of the human immunodeficiency virus (HIV) surface protein, gp 120, constitutes a principal neutralizing determinant. HIV strains lacking a naturally conserved N-linked oligosaccharide (at position 306) within the V3 loop are highly sensitive to neutralization. We subjected molecular clones of HIV(LAI) lacking this 306N-glycan to in vitro immune selection with MAbs directed against the V3 loop. In all, ten clones were characterized, and all proved resistant to V3-directed neutralization. Sequencing of the V3 loop revealed that six of the clones had become resistant at least partly by reacquisition of the 306N-glycan. Only two of the clones possessed mutations within the binding site of the antibody itself, while the two remaining clones did not display changes within the V3 loop itself. Thus, HIV strains lacking the 306N-glycan primarily develop resistance to V3-directed neutralization through acquisition of the specific oligosaccharide. This demonstrates that protein glycosylation can be a primary modifier of virus antigenicity of possible importance for the interaction of HIV with the host immune response.

Amino Acid Sequence↗
PubMed1996

Erythrocyte removal and blood clearance in the endolymphatic sac. An experimental and TEM study.

The endolymphatic sac (ES) appears to serve as an immunologic/phagocytic defence organ. This may involve both specific and unspecific cell reactions for removal of both endogenous waste products and debris and foreign material. The present study was carried out in order to investigate whether the ES is involved in the removal of blood from the inner ear. The round window was exposed and the stapedial artery experimentally lesioned to cause bleeding. The ES was taken out after various time intervals and analyzed by TEM and LM, care being taken to maintain the structural integrity at all levels. This was done in order to see if the endolymphatic sac is involved in the removal of blood from the inner ear. The results indicate that the ES possesses hitherto unknown specific cellular properties for the disposal of blood and blood corpuscles. It is believed that this system may represent an important physiological function for regulation of homeostatic equilibrium around the inner ear sensory structures. The results also offer further support for the existence of a longitudinal "flow" of endolymph from the cochlea into the ES. Judging from the time it takes for erythrocytes to appear in the duct and sac, this flow would seem to take about 1-2 h in the mouse.

Animals↗
PubMed1996

Sunbed use in relation to phenotype, erythema, sunscreen use and skin diseases. A questionnaire survey among Swedish adolescents.

Sunbed use was studied in relation to phenotype, erythema, sunscreen use and skin disease. The study population comprised 14-19 year-old Stockholm adolescents in 60 randomly selected classes, with 1252 students providing information. More than half (57%) reported sunbed use > or = 4 times during the previous year. Skin type III dominated (64%). Excessive exposure (> or = 10 times/year) was not correlated to skin type. Sunscreens were most commonly used by sunbed users. Of all sunbed users, 44% reported erythema. Adolescents with acne/seborrhoca, eczema or psoriasis used sunbeds more than others without skin diseases. The proportion with sunbed erythema (44%) indicates an unrecognized susceptibility to artificial ultraviolet radiation (UVR) among adolescents. The association between high exposure to UVR and sunscreen use stresses the importance of sunscreens being used as supplementary protection, not as a tool for tanning.

Adolescent↗
PubMed1996

Potassium, sodium, and cancer: a review.

Agents known or believed to be carcinogenic decrease the concentration of potassium and increase the concentration of sodium in the cells. Anticarcinogenic agents have the opposite effect. In all cases where we have information on an agent's carcinogenicity or anticarcinogenicity and on that agent's effects on cellular potassium and sodium concentrations the above relationships have been found to be true. Dietary carcinogenic agents studied include sodium, cadmium, fat, cholesterol, calories, and alcohol; dietary anticarcinogenic agents include potassium, vitamins A, C, and D, selenium, and fiber. The effect of calcium intake is less clear as that effect depends on the concentrations on sodium and potassium. Not only dietary agents but also other carcinogenic and anticarcinogenic agents work in the same way. The cancer-causing drug dimethylhydrazine increases sodium and decreases potassium in the cells, whereas, for example, indomethacin, an anticarcinogen, has the opposite effect. In aging potassium leaves the cells, sodium enters them, and the rates of cancer increase. Patients with hyperkalemic diseases (Parkinson, Addison) have reduced cancer rates, and patients with hypokalemic diseases (alcoholism, obesity, stress) have increased cancer rates.

Animals↗
PubMed1994

Treatment of alcoholism.

Special problems in the treatment of alcoholism are discussed. Risk groups, for instance children of alcoholics, should be identified as early as possible so that special attention can be paid to them. Treatment motivation plays a very central role, and motivating a patient for long-term treatment often is the most difficult part of the work. For alcohol dependent alcoholics, total abstinence should be the goal of treatment. To achieve this, psychotherapy consisting of supportive, behavioral and dynamic elements is recommended. To achieve effective therapy it should be carried out for a considerable length of time.

Alcoholism↗
PubMed1994

Identification of three N-linked glycans in the V4-V5 region of HIV-1 gp 120, dispensable for CD4-binding and fusion activity of gp 120.

Site-directed mutagenesis was used to study the biological significance of three N-linked glycans (linked to Asn406, Asn448, and Asn463), situated in the CD4-binding region of gp120. Mutagenesis was carried out in a phage M13 system, and the mutated env genes were inserted into recombinant vaccinia virus (r-vaccinia virus). To evaluate if the level of expression affected the biological phenotype of mutant gp120, we expressed the envelope glycoproteins using either a weak (7.5 K) or a strong (11 K) promoter of vaccinia virus. The expression of mutated env proteins was analyzed after infecting CD4-expressing HeLa cells with the r-vaccinia virus, by monitoring the ability of the infected cells to generate CD4-dependent syncytia. Env gene products lacking all three glycans as well as env gene products lacking different permutations of one or two glycans were analyzed. All mutated gp120 species had the expected electrophoretical mobility as anticipated from elimination of one, two, and three N-linked glycans, respectively. Moreover, all mutant env gene products demonstrated the same capacity to induce formation of syncytia, irrespective of using the weak or strong promoter for expression. These data indicate that the three N-linked glycans studied are dispensable for HIV env gene products to function in CD4-binding and the subsequent fusion step.

Amino Acid Sequence↗
PubMed1994

Identification of an N-linked glycan in the V1-loop of HIV-1 gp120 influencing neutralization by anti-V3 antibodies and soluble CD4.

Glycosylation is necessary for HIV-1 gp120 to attain a functional conformation, and individual N-linked glycans of gp120 are important, but not essential, for replication of HIV-1 in cell culture. We have constructed a mutant HIV-1 infectious clone lacking a signal for N-linked glycosylation in the V1-loop of HIV-1 gp120. Lack of an N-linked glycan was verified by a mobility enhancement of mutant gp120 in SDS-gel electrophoresis. The mutated virus showed no differences in either gp120 content per infectious unit or infectivity, indicating that the N-linked glycan was neither essential nor affecting viral infectivity in cell culture. We found that the mutated virus lacking an N-linked glycan in the V1-loop of gp120 was more resistant to neutralization by monoclonal antibodies to the V3-loop and neutralization by soluble recombinant CD4 (sCD4). Both viruses were equally well neutralized by ConA and a conformation dependent human antibody IAM-2G12. This suggests that the N-linked glycan in the V1-loop modulates the three-dimensional conformation of gp120, without changing the overall functional integrity of the molecule.

Amino Acid Sequence↗
PubMed1993

The interaction between different domains of staphylococcal protein A and human polyclonal IgG, IgA, IgM and F(ab')2: separation of affinity from specificity.

Binding properties of staphylococcal protein A (SpA) to different human immunoglobulins have been investigated. In this analysis, intact SpA as well as SpA-derived fragments containing one to five IgG-binding domains of different compositions, were used. The affinity binding constants of the different proteins to human polyclonal IgG, IgA, IgM and F(ab')2-fragments as well as their binding capacity to the immunoglobulin molecules were determined. The results show that although all the proteins bound to IgG, regardless of size or composition, the binding strength differed significantly. Proteins containing five domains have a stronger affinity for IgG than those containing one or two. There were no marked differences in binding strength between different domains. However, the binding ability to IgA and IgM showed a marked difference between the various SpA-derived proteins of different compositions. This discrepancy was correlated to differences in their relative binding properties to isolated F(ab')2-fragments of IgG. Hence, we conclude that the binding affinity is mainly affected by the number of domains, whereas the binding specificity is to a large extent determined by which domains are selected.

Antibody Affinity↗
PubMed1993

Role of serotonin in the regulation of interferon-gamma production by human natural killer cells.

Monocytes, recovered directly from peripheral blood by counter-current centrifugal elutriation (CCE), were shown to provide two regulatory signals for induction of interferon-gamma (IFN-gamma) in natural killer (NK) cells in response to interleukin-2 (IL-2): an upregulating signal and an inhibitory signal. The inhibitory signal was time-dependent, irreversible, and operating on a pretranslational level, as indicated by the inability of enriched NK cells to accumulate IFN-gamma mRNA in the presence of elutriated monocytes. Monocyte-induced inhibition of IFN-gamma production was abrogated by the biogenic amine serotonin, acting via the 5-hydroxytryptamine, or serotonin (5-HT1A), subset of serotonin receptors (5-HTR). Thereby, serotonin effectively promoted IFN-gamma production in the presence of monocytes. We conclude that serotonergic 5-HT1A receptors transduce signals that are required for NK cells to produce IFN-gamma in response to IL-2.

Cell Communication↗
PubMed1993

Mutational analysis of the interaction between staphylococcal protein A and human IgG1.

The interactions have been studied between an IgG-binding domain derivative based on domain B of staphylococcal protein A (designated Z) and human immunoglobulin G class 1 (IgG1) and its Fc fragment (Fc1) respectively. Five single amino acid substituted mutant forms of Z were constructed at the gene level, produced intracellularly in Escherichia coli, purified to homogeneity and characterized. Four of these Z variants, designated Z(L17D), Z(N28A), Z(I31A) and Z(K35A), were mutated in residues suggested to be involved in binding, based on the three-dimensional structure of the complex between a one domain protein A molecule and Fc1 [Deisenhofer, J. (1981) Biochemistry, 20, 2361-2370]. The fifth mutant protein, Z(F30A), had a mutation in a phenylalanine residue which was not expected to be involved in the interaction. Analysis by far UV circular dichroism spectroscopy suggests that all Z mutant proteins have similar folds. Their respective binding to human monoclonal IgG1 and to human recombinant Fc1 were studied in a competitive binding assay using radioactively labeled Z as a tracer, demonstrating that the mutant proteins with a substitution in the postulated binding surface showed a weakened binding to both the full-length antibody and the recombinant Fc1. The affinity constants of the interactions as well as relative binding free energies from the parent Z molecule were calculated. These values were similar for each Z variant to both IgG1 and Fc1, suggesting that Fc and not Fab binding was measured also for IgG1. However, the binding strengths differ significantly, and these binding properties were used to compare the contribution of each mutated amino acid residue in the Fc interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Endolymphatic sac morphology after instillation of hyperosmolar hyaluronan in the round window niche.

One hundred and sixty-eight mice were injected with hyaluronan (HA) of varying tonicity in the middle ear and compared with 81 control animals to study the effects of hypertonic solutions in the middle ear on inner ear fluid homeostasis and endolymphatic sac (ES) response. Six hours after 1.9% HA and 4, 6 and 8 h after 4% HA deposition there was a significant increase in the proportion of granule-containing light epithelial cells in the ES as compared with controls indicating an enhanced secretory activity from the epithelial lining. Six, 8 and 10 h after deposition of 4% HA, the ES volume was significantly reduced. The secretory activity and the ability of the ES to vary its volume could be specific responses to dehydration of the inner ear resulting from the high colloid osmotic pressure exerted by concentrated HA. The secretion of high-molecular substances into the ES may serve to keep the ES lumen patent and thus ensure a proper ES function and/or to regulate the intralabyrinthine volume and fluid pressure. Whether the findings may have clinical relevance for Ménière's patients remains to be elucidated.

Animals↗