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J Alfredsson

Publications and source records attributed to J Alfredsson.

8 recordsLinked to original sources
PubMed2006

IgE-receptor activation of mast cells regulates phosphorylation and expression of forkhead and Bcl-2 family members.

Activation of the high-affinity IgE-receptor, FcepsilonRI, expressed on mast cells can result in either enhanced survival or apoptosis depending on the circumstances. In this study, we have analysed signalling pathways involved in the regulation of mast cell survival and apoptosis. FcepsilonRI cross-linking induces phosphorylation of Akt and its downstream target forkhead transcription factors. In addition, Bad, GSK-3beta and IkappaB-alpha also become phosphorylated. A1, a prosurvival Bcl-2 homologue transcriptionally controlled by NFkappaB transcription factors, is upregulated upon FcepsilonRI activation. These events have prosurvival effects on the mast cells. Moreover, FcepsilonRI activation upregulates the levels of the proapoptotic protein Bim and induces a rapid, but transient, phosphorylation of Bim. Thus, FcepsilonRI activation of mast cells leads to both prosurvival and proapoptotic signalling events where the outcome most likely depends on the balance between these signals.

Animals↗
PubMed2005

Proapoptotic Bcl-2 family member Bim is involved in the control of mast cell survival and is induced together with Bcl-XL upon IgE-receptor activation.

Mast cells play critical roles in the regulation of acute and chronic inflammations. Apoptosis is one of the mechanisms that limit and resolve inflammatory responses. Mast cell survival can be controlled by growth factors and activation of the IgE-receptor FcvarepsilonRI. Members of the Bcl-2 protein family are critical regulators of apoptosis and our study provides evidence that the proapoptotic BH3-only family member Bim is essential for growth factor deprivation-induced mast cell apoptosis and that Bim levels increase upon FcvarepsilonRI activation. Bim deficiency or Bcl-2 overexpression delayed or even prevented cytokine withdrawal-induced mast cell apoptosis in culture. The prosurvival protein Bcl-XL and the proapoptotic Bim were both induced upon FcvarepsilonRI activation. These results suggest that Bim and possibly also other BH3-only proteins control growth factor withdrawal-induced mast cell apoptosis and that the fate of mast cells upon FcvarepsilonRI activation depends on the relative levels of pro- and antiapoptotic Bcl-2 family members.

Animals↗
PubMed2001

Stem cell factor-induced migration of mast cells requires p38 mitogen-activated protein kinase activity.

Stem cell factor (SCF) can be considered a cardinal cytokine in mast cell biology as it affects mast cell differentiation, survival, and migration. The objective of this study was to investigate the role of two mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase (ERK) and p38, in SCF-induced cell migration. This was examined in mouse mast cells by using PD 098059 and SB203580, which are specific inhibitors of mitogen-induced extracellular kinase (MEK) and p38 MAP kinase, respectively. SCF induced a rapid and transient activation of ERK and p38 in a dose-dependent manner. Inhibition of p38 activity by SB203580 was paralleled with a marked reduction of migration toward SCF, whereas the effect of the MEK inhibitor was less pronounced. This is the first report of a physiological function of SCF-dependent activation of p38. Whether p38-mediated mast cell migration is a possible target for suppression of mast cell hyperplasia remains to be determined.

Animals↗
PubMed2000

A polymorphic region in the human transcription factor AP-2beta gene is associated with specific personality traits.

Transcription factor AP-2beta is implicated in playing an important role during embryonic development of different parts of the brain, eg, midbrain, hindbrain, spinal cord, dorsal and cranial root ganglia.1,2 The gene encoding AP-2beta contains a polymorphic region which includes a tetranucleotide repeat of [CAAA] four or five times, located in intron 2 between nucleotides 12593 and 12612.3 Since the midbrain contains structures important for variables such as mood and personality, we have investigated if the AP-2beta genotype is associated with personality traits estimated by the Karolinska Scales of Personality (KSP). Identification of transcription factor genes as candidate genes in psychiatric disorders is a novel approach to further elucidate the genetic factors that, together with environmental factors, are involved in the expression of specific psychiatric phenotypes. The AP-2beta genotype and KSP scores were determined for 137 Caucasian volunteers (73 females and 64 males). The personality traits muscular tension, guilt, somatic anxiety, psychastenia and indirect aggression were significantly associated with the specific AP-2beta genotype, albeit with significant difference between genders. Based on this result the human AP-2beta gene seems to be an important candidate gene for personality disorders. Moreover, the present results suggest that the structure of the intron 2 region of the AP-2beta gene is one factor that contributes to development of the constitutional component of specific personality traits.

Adult↗
PubMedDate not supplied

Incidence of spontaneous abortion following artificial insemination by donor.

This study examines the frequency of spontaneous abortions in pregnancies achieved by artificial inseminations with donor semen (AID), with special respect to the use of cryopreserved semen and ovulation induction with clomiphene citrate. The abortion rate was found to be similar in AID series using frozen semen to those using fresh semen, nor was the rate increased in composite AID series (both fresh and frozen semen) when compared with the rate of spontaneous abortions in the general population. When clomiphene was used, the abortion rate was increased only in groups of anovulatory and irregularly ovulating women. Those AID series where all women treated are given clomiphene show no increase in abortion rates. The discussion is focused on factors that influence the abortion rate and on possible etiological factors.

Abortion, Spontaneous↗