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Biomedical subjects

E Andersson

Publications and source records attributed to E Andersson.

At least 73 records · Page 4Linked to original sources

Progesterone stimulates GABA uptake in human spermatozoa.

Progesterone can initiate the mammalian sperm acrosome reaction in vitro, and studies on the effect of progesterone and several other steroids have demonstrated an increased calcium influx following binding to the sperm membrane. We have previously presented data indicating the presence of a GABA transport protein in human spermatozoa. In this study, we have examined the uptake of radiolabelled GABA into human spermatozoa in the presence of progesterone, other steroids known to elevate intracellular calcium, and steroids known to be ineffective as stimulators of calcium influx. The results demonstrate a twofold increase in GABA uptake following preincubation with progesterone or steroids known to stimulate calcium influx. Steroids with minor effects on calcium influx were less effective as stimulators of GABA uptake.

Biological Transport↗

Immunoglobulin production induced by CD57+ GC-derived helper T cells in vitro requires addition of exogenous IL-2.

Germinal centers (GC) are well-defined areas in lymphoid organs were B cells proliferate and differentiate in response to T-cell-dependent antigens. The GC comprises B cells, follicular dendritic cells, tangible body macrophages, and a low number of CD4+ T cells. A large portion of these T cells expresses CD57. We have examined the ability of the CD4+ CD57+ GC T cells to become activated and to take part in B cell activation processes. These T cells coexpress CD45RO, CD69, CD28, and upon mitogenic stimulation CD25. The cell population was found neither to contain nor to be able to produce any specific mRNA for IL-2, IL-4, and IFN-gamma upon activation. Levels of mRNA encoding CD40 ligand was also undetectable under similar conditions. Furthermore, in contrast to ordinary CD4+ T cells, this population expressing CD57 was unable to induce B cells to Ig production in the presence of pokeweed mitogen or SEA unless IL-2 was added to the cultures. However, despite their apparent lack of function CD4+ CD57+ GC T cells were found to rescue GC B cells from cell death in vitro to the same extent as CD4+ CD57+ Th cells. The phenotypical and functional differences found between these Th cells and regular Th-cells suggest that they either represent a T cell subset with distinct properties within the GC yet to be determined or that they represent T cells, late in the immune response, having lost most of their original functions and capabilities.

B-Lymphocytes↗

Carrier-mediated gamma-aminobutyric acid uptake in human spermatozoa indicating the presence of a high-affinity gamma-aminobutyric acid transport protein.

Human spermatozoa are capable of a carrier-mediated gamma-aminobutyric acid (GABA) uptake. The uptake is dependent on the concentration of Cl- and Na+ in the external medium, and the kinetics of the carrier resembles high-affinity GABA transport proteins. The time-dependent uptake of GABA displays large interindividual differences and is not correlated to motility parameters or morphology in the individual sample. Incubation of human spermatozoa with radiolabeled GABA was performed. Swim-up preparations of human spermatozoa were incubated with [3H]GABA, and subsequent GABA uptake was measured at various times by scintillation counting. GABA was accumulated intracellularly, and the uptake could be inhibited by preincubation of the samples in 200 microM nipecotic acid. Addition of aminooxyacetic acid in the medium did not alter the results, indicating that the internalized GABA remained unmetabolized intracellularly throughout the observation period. Kinetic analysis of GABA uptake was performed, and the Km for GABA transport was 14 microM. GABA uptake was reduced by equimolar substitution of NaCl in the capacitating medium by KCl, choline chloride, LiCl, N-methyl-D-glucamine (HCl) or D-glucuronic acid (sodium salt). Maximal reduction of [3H]GABA uptake was observed when the Na+ fraction of the medium was replaced with KCl. The results indicate the presence of a high-affinity GABA transport protein in the plasma membrane of human spermatozoa. GABA uptake was subsequently measured in 30 individual semen samples from men of barren couples. Large interindividual differences in GABA uptake was observed, but GABA uptake was not correlated to motility parameters or to morphology in the individual samples analyzed.

Carrier Proteins↗

Increased concentrations of 3,4-didehydroretinol and retinoic acid-binding protein (CRABPII) in human squamous cell carcinoma and keratoacanthoma but not in basal cell carcinoma of the skin.

Retinoids are biologic response modifiers that are present in normal skin and may possibly be perturbed in carcinogenesis. To examine this possibility in human skin, we analyzed vitamin A and cytosolic retinoid binding proteins (cellular retinol binding protein and cellular retinoic acid binding protein [CRABP]) in a total of 38 non-melanoma skin tumors and 25 healthy skin samples using high performance liquid chromatography, radioligand electrophoresis, and reverse transcriptase-polymerase chain reaction. The mean +/- SEM retinol concentration was normal in basal cell carcinoma (0.60 +/- 0.10 microM) and seborrheic keratosis (0.47 +/- 0.07 microM), but increased in keratoacanthoma (1.60 +/- 0.41 microM) and squamous cell carcinoma (1.17 +/- 0.28 microM) (p < 0.05 for both). Also, the concentrations of 3,4-didehydroretinol, a major vitamin A metabolite produced in human skin, were markedly elevated (6-7 times normal) in keratoacanthoma and squamous cell cancer. All types of tumors showed moderately increased levels of cellular retinol binding protein. In addition, keratoacanthoma and squamous cell cancer showed markedly increased levels (6-7 times normal) of CRABPII protein. Transcriptional activity of the CRABPII gene was demonstrated in both normal and neoplastic epidermis, but clear CRABPI mRNA expression was found only in basal cell carcinoma. The data indicate that characteristic perturbations of the vitamin A and retinoid binding protein levels occur in squamous cell-derived skin tumors, but whether these reflect intrinsic errors in retinoid metabolism or are secondary to abnormal cellular differentiation is unknown.

Aged↗

Pleural mesotheliomas are underreported as occupational cancer in Sweden.

The aim of this study was to estimate to what degree malignant pleural mesotheliomas were reported as occupational cancers. The study included all malignant pleural mesotheliomas (n = 210) found in the Cancer Registry 1980-1989 from four Swedish counties. Whether or not a case was reported as occupational cancer was found in the Swedish Register of Reported Occupational Diseases. To evaluate the presence of exposure histories, the chest department files for 58 mesotheliomas from one county were reviewed. The reporting was low, with only 75 mesotheliomas (36%) reported. All the cases were men, and for the men, the reporting frequency was 42%. The reporting was significantly lower for the last part of the decade than for the first part. The reporting frequency decreased with age. In the review of the chest department files, an exposure history was found in 93% of the reported cases and in 47% of the unreported cases. It is concluded that physicians must give more priority to exposure histories in patients with pleural mesotheliomas.

Adult↗

CD4+CD57+ T cells derived from peripheral blood do not support immunoglobulin production by B cells.

A small subpopulation of CD4+ T cells found in peripheral blood coexpresses the CD57+ marker normally found on, e.g., NK cells. It is known that this population occurs in a higher frequency in certain diseases. The same antigen has also been shown to be expressed on CD4+ T cells derived from germinal centers. The localization of this cell population to specialized lymphoid structures suggests that it may play a role in the evolution of the antibody response following antigenic stimulation in vivo. We have examined the ability of peripheral blood helper T cells coexpressing CD57 to participate in B cell activation/differentiation and evaluated their responses to polyclonal stimulation. The CD4+CD57+ T cells do not express mRNA for a number of different cytokines or for the CD40 ligand after activation in vitro. Furthermore these cells do not induce differentiation of B cells into immunoglobulin-producing cells. Consequently, despite their CD4 phenotype and their ability to be activated, to express the IL-2 receptor, and to enter into the cell cycle, they do not act as T helper cells under conditions where CD4+/CD57- cells normally do so. The findings suggest that this peripheral blood helper T cell population is functionally different from regular CD4+ T cells. The basis for the lack of proper costimulatory signals for immunoglobulin production might be related to the low expression of CD28.

Antigens, CD↗

Evolution of immunoglobulin heavy chain variable region genes: a VH family can last for 150-200 million years or longer.

Many immunoglobulin variable region (IgV) genes are present in the vertebrate genome and provide a basis for antibody diversity. IgV genes have been classified into distinct families according to DNA sequence similarity. Comparisons of VH and VL genes from two mammalian species (mouse and human) have led to the conclusion that some V gene families are stable over 65 million years of evolution. Here we show that a VH family can be stable for 150-200 million years or longer. This conclusion is drawn from our extensive comparison of VH genes between two species of low vertebrates (rainbow trout and catfish), and from the estimation of species divergence time by the substitution rate of an IgM constant domain. The estimated speed of VH gene evolution explains the moderate degree of sequence similarity in VH gene families between a mammal (mouse) and a teleost (rainbow trout). The distribution of species-specific amino acid residues in certain VH families indicates that the process of sequence homogenization plays a major role in shaping the V gene family.

Amino Acid Sequence↗

Evidence for gamma-aminobutyric acid specific binding sites on human spermatozoa.

The possible presence of gamma-aminobutyric acid (GABA) specific binding sites on human spermatozoa was investigated. Swim-up preparations of human spermatozoa were incubated with radiolabelled GABA in the presence of unlabelled GABA, alternatively displacers of GABAA/B receptors and GABA transport proteins. The results indicate that GABA specific binding sites are present on the surface of human spermatozoa, and that these binding sites possibly indicate the presence of GABA transport proteins. Furthermore, GABA at different concentrations was added to swim-up preparations of human spermatozoa. Possible effects of GABA on sperm motility, hyperactivation and acrosome reaction were explored. No significant differences were observed between treated groups and controls concerning motility parameters and hyperactivation. Incubation with GABA did not cause any increase in spontaneous acrosome reaction. However, spermatozoa treated with the calcium ionophore A-23187 showed a small but significantly increased ability to undergo the acrosome reaction following preincubation in 10(-4) M GABA (P < 0.05).

Acrosome↗

Nasal cytokines in common cold and allergic rhinitis.

Coronavirus-induced common cold and allergen-induced rhinitis are characterized by nasal mucosal exudation of bulk blood plasma. The mucosal exudation process involves 'flooding' of the lamina propria with plasma-derived binding proteins and it is possible that subepithelial inflammatory cytokines and mediators may be moved by the exudate to the mucosal surface. In this study, we have analysed cytokine levels in nasal lavage (NAL) fluids from non-allergic subjects inoculated with coronavirus (n = 20) and from subjects with allergic (birch pollen) rhinitis subjected to additional allergen challenge (samples were obtained 35 min post challenge) in the laboratory (n = 10). Ten of the 20 inoculated subjects developed common cold and 10 remained healthy. Interferon-gamma (IFN gamma), interleukin-1 beta (IL-1 beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, and IL-6 were analysed in unprocessed NAL fluids using immunoassays. The subjects who developed common cold had increased NAL fluid levels of IFN gamma (P < 0.05) that correlated well with the symptoms (P < 0.001). IFN gamma did not increase in subjects with allergic rhinitis. IL-1 beta levels were similar in NAL fluids obtained from all inoculated subjects. In the subjects with allergic rhinitis NAL fluid levels of both IL-1 beta and GM-CSF were increased (P < 0.05). GM-CSF was not detected in common cold. IL-4 and IL-6 were not detectable in any of the NAL fluids. The present cytokines may not only emanate from superficial mucosal cells. By aiding plasma exudation subepithelial cytokines may potentially also be retrieved on the mucosal surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The role of the psoas and iliacus muscles for stability and movement of the lumbar spine, pelvis and hip.

The activation patterns of the psoas and iliacus muscles were investigated in 7 healthy adult subjects (4 men and 3 women) during a variety of motor tasks in standing, sitting and lying. Myoelectric activity was recorded simultaneously from the 2 muscles using thin wire electrodes inserted under guidance of high-resolution ultrasound. In general, both muscles were coactivated, albeit to different relative levels, particularly when hip flexor torque was required. Selective activation of the iliacus could, however, be seen to stabilize the pelvis in contralateral hip extension during standing. Psoas was found to be selectively involved in sitting with a straight back and in contralateral loading situations requiring stabilization of the spine in the frontal plane. During training exercises from a supine position, such as sit-ups, the contribution of the psoas and iliacus muscles could be varied by changing the range of motion as well as the position and support for the legs. Thus, the 2 anatomically different muscles of the iliopsoas complex were shown to have individual and task-specific activation patterns depending on the particular demands for stability and movement at the lumbar spine, pelvis and hip.

Adult↗

Inflammatory signs in wet smear and Pap-smear compared with the histopathology from the female lower genital tract.

In order to define the relationship between various criteria of female lower genital tract inflammation, we examined wet smears, cervical smears and biopsies from 131 patients. The presence of clue cells in rehydrated dry smears showed a positive correlation to the presence of clue cells in Papanicolaou stained smears, and to some extent with cytological evidence of inflammation (Kappa 0.48). Cytological inflammatory findings correlated well with the presence of clue cells in rehydrated dry smears, but signs of inflammation diagnosed by histopathology did not correspond to findings in cytological smears, probably because these methods reveal inflammation at different sites.

Analysis of Variance↗

The metabolism of vitamin A to 3,4-didehydroretinol can be demonstrated in human keratinocytes, melanoma cells and HeLa cells, and is correlated to cellular retinoid-binding protein expression.

Conversion of retinol to 3,4-didehydroretinol is probably a rate-limiting step in the formation of 3,4-didehydroretinoic acid, a candidate ligand for nuclear retinoid receptors in human epidermal keratinocytes. To investigate whether this metabolic pathway also exists in other cell systems, we compared the retinoid concentrations and the bioconversion of [3H]retinol to [3H]3,4-didehydroretinol in human primary keratinocytes, human cervical carcinoma (HeLa) cells, human melanoma (JKM86-4) cells, monkey kidney epithelium (CV-1) cells, and murine teratocarcinoma (F9) cells. The cellular retinol concentration ranged from 2.33 to 99.1 pmol/mg protein with the highest values observed in keratinocytes. 3,4-Didehydroretinol was only detected in cells of human origin and its concentration ranged from 0.24 pmol/mg in HeLa to 34.6 pmol/mg in the keratinocytes. Incubation with [3H]retinol for 1-24 h resulted in a rapid appearance of [3H]3,4-didehydroretinol in human keratinocytes, and to a lesser extent in HeLa and melanoma cells, but not in the other cells. Analysis of cellular retinol- and retinoic acid-binding protein concentrations showed a correlation to the cells' ability to accumulate 3,4-didehydroretinol, suggesting a role for these proteins in the 3,4-didehydro metabolic pathway. The combined results suggest that although 3,4-didehydroretinol is most typical for human keratinocytes, studies of its metabolism are also feasible in HeLa cells which contain low levels of retinoid-binding proteins.

Animals↗

Isolation, characterization and expression of cDNAs encoding the catfish-type and chicken-II-type gonadotropin-releasing-hormone precursors in the African catfish.

The cDNAs encoding the catfish prepro-gonadotropin-releasing hormone and the chicken prepro-gonadotropin-releasing hormone II of the African catfish (Clarias gariepinus) have been isolated and sequenced. The catfish gonadotropin-releasing-hormone precursor and the chicken gonadotropin-releasing-hormone-II precursor have the same overall architecture as other gonadotropin-releasing-hormone precursors identified so far; each is composed of a signal peptide, gonadotropin-releasing hormone and a gonadotropin-releasing-hormone-associated peptide which is connected to gonadotropin-releasing hormone and chicken gonadotropin-releasing hormone II, in combination with the Gly-Lys-Arg sequence, are highly conserved during evolution when compared with the corresponding regions of mammalian, avian (chicken gonadotropin-releasing hormone I) and other fish gonadotropin-releasing-hormone precursors. However, the gonadotropin-releasing-hormone-associated peptide regions are markedly divergent. Northern-blot analysis revealed the presence of a single catfish gonadotropin-releasing-hormone mRNA species of about 470 bases, and the presence of a single chicken gonadotropin-releasing-hormone-II mRNA species of about 650 bases in the African catfish brain. In situ hybridization revealed catfish gonadotropin-releasing-hormone cell bodies rostro-caudally scattered in the olfactory nerve, along both sides of the midline of the telencephalon, in the preoptic area of the ventral hypothalamus, and in the infundibular stalk close to the pituitary. Chicken gonadotropin-releasing-hormone-II cell bodies, however, were exclusively found in the midbrain tegmentum.

Amino Acid Sequence↗