Biomedical subjects

Göran Berg

Publications and source records attributed to Göran Berg.

12 recordsLinked to original sources

PubMed2007

CD4+ CD25+ regulatory T cells in human pregnancy: development of a Treg-MLC-ELISPOT suppression assay and indications of paternal specific Tregs.

The current study was aimed at developing a one-way mixed leucocyte culture-enzyme-linked immunospot (MLC-ELISPOT) assay for the study of CD4(+) CD25(+) regulatory T (T(reg)) cells and applying this method in the study of antifetal immune reactions during human pregnancy. Twenty-one pregnant women and the corresponding fathers-to-be, and 10 non-pregnant control women and men, participated in the study. CD4(+) CD25(+) cells were isolated from peripheral blood mononuclear cells (PBMC) by immunomagnetic selection. Maternal/control PBMC were stimulated with paternal or unrelated PBMC in MLC. Secretion of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) from responder cells, with or without the presence of autologous T(reg) cells, was analysed by ELISPOT. PBMC from pregnant women showed increased secretion of IL-4 compared to controls. In pregnant and non-pregnant controls, T(reg) cells suppressed IFN-gamma reactivity against paternal and unrelated alloantigens. Interestingly, T(reg) cells suppressed IL-4 secretion against paternal but not unrelated alloantigens during pregnancy. We have successfully developed a model for studying T(reg) cells in antifetal cytokine reactions during pregnancy. Results indicate that T(reg) cells contribute to strict regulation of both T helper type 1-like and type 2-like antifetal immune reactions. Interestingly, T helper type 2-like cells specific to unrelated alloantigens are able to escape the suppression of T(reg) cells, which would allow for IL-4, alongside CD4(+) CD25(+) T(reg) cells, to control potentially detrimental IFN-gamma reactions during pregnancy.

Adolescent↗

PubMed2006

Cytokine mapping of sera from women with preeclampsia and normal pregnancies.

INTRODUCTION: Preeclampsia is a pregnancy-specific syndrome. The immune system in preeclampsia is changed with an increased innate activity and there is a hypothesis of a shift towards Th1-type immunity. The aim of this study was to determine a spectrum of soluble immunological factors denoting different aspects of immune activation in third trimester sera from women with preeclampsia (N=15) and compare with levels in sera from normal pregnant women (N=15). MATERIAL AND METHODS: IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p40, IL-13, IL-15, IL-17, IFN-alpha, IFN-gamma, TNF-alpha, GM-CSF, MIP-lalpha, MIP-1beta, MCP-1, eotaxin and RANTES were measured in serum using multiplex bead arrays. The levels of soluble CD14 and soluble IL-4 receptor were measured by enzyme-linked immunoassay (ELISA). RESULTS: Preeclamptic women had significantly increased levels of circulating IL-6 (p=0.002), IL-8 (p=0.003) and soluble IL-4R (p=0.037), compared to women with normal pregnancies. CONCLUSION: This study supports the hypothesis of increased inflammatory responses in preeclampsia, illustrated by the increased levels of IL-6 and IL-8. The finding of increased levels of soluble IL-4 receptor is an intriguing finding with several interpretations, which may partly support the hypothesis of a Th1 shift in preeclampsia.

Adult↗

PubMed2006

Size of delivery unit and neonatal outcome in Sweden. A catchment area analysis.

BACKGROUND: Quality of perinatal care was evaluated in relation to size of delivery unit and size of catchment area for deliveries. METHODS: Neonatal outcome, measured as neonatal mortality, low Apgar scores at 5 min, and the occurrence of respiratory disorders and cerebral palsy was analyzed during a 15-year period from 1985 to 1999 inclusive. Figures were derived from the Swedish Medical Birth Registry and the Hospital Discharge Registry. Odds ratios were estimated for the different outcomes in relation to size of delivery unit (actual and estimated number of births) and the provision of a pediatric department at the hospital. Seven possible confounders were considered: year of birth, maternal age, parity, smoking during pregnancy, gestational age, parental cohabitation, and maternal body mass index. RESULTS: Neonatal mortality was significantly higher for infants in families living within the catchment area of the smallest units without a pediatric department. Small differences in the occurrence of respiratory disturbances and Apgar scores are probably due to diagnostic differences. There were no differences in the incidence of cerebral palsy. Neonatal mortality continued to decrease during the observation period. CONCLUSIONS: Differences were minor, pointing to a fairly homogeneous quality of perinatal care and an efficient referral system for risk pregnancies. Mortality continues to decrease in spite of a reduction in the number of units caring for deliveries.

Adult↗

PubMed2005

Indications of an altered immune balance in preeclampsia: a decrease in in vitro secretion of IL-5 and IL-10 from blood mononuclear cells and in blood basophil counts compared with normal pregnancy.

It has been suggested that maladaptation of the maternal immune response during pregnancy might be a causal factor for preeclampsia. This study was designed to examine the systemic immune status at both the innate level and the adaptive level in pregnancies complicated by preeclampsia (n=15) and normal pregnancies (n=15). Spontaneous and in vitro-induced secretion of IL-5, IL-6, IL-10, IL-12, IL-13 and TNF-alpha, in response to paternal blood cells and the vaccination antigens purified protein derivate of tuberculin (PPD) and tetanus toxoid (TT), was detected in cell culture supernatants from blood mononuclear cells by ELISA. Preeclamptic women showed reduced numbers of basophil granulocytes in the blood (p=0.004) and lower spontaneous secretion of IL-5 from blood mononuclear cells (p=0.016). In addition, paternal antigen-induced secretion of IL-10 was decreased in preeclampsia compared with normal pregnancy (p=0.012). No further differences between preeclampsia and normal pregnancy were found for any stimuli or cytokines. The present findings of reduced basophil numbers and lower spontaneous in vitro secretion of IL-5 in preeclampsia compared with normal pregnancy indicate a decrease in systemic Th2 immunity in preeclampsia. Furthermore, the decrease in paternal antigen-induced secretion of the immunosuppressive cytokine IL-10 in preeclampsia indicates a fetus-specific decrease in immunosuppression mediated by blood mononuclear cells. Whether these systemic changes are a cause or a consequence of preeclampsia remains to be elucidated.

Basophils↗

PubMed2005

Obstetric anal sphincter injury ten years after: subjective and objective long term effects.

OBJECTIVE: To establish the long term effects of obstetric anal sphincter rupture. DESIGN: Prospective observational study. SETTING: University hospital in Sweden. POPULATION: Eighty-two women from a prospective study from 1990 to compare anorectal function after third degree tear. METHODS: Women completed a structured questionnaire, underwent a clinical examination and anorectal manometry, endoanal ultrasound (EAUSG) with perineal body measurement. MAIN OUTCOME MEASURES: Symptoms of anal incontinence, sexual symptoms, anal manometry scores and evidence of sphincter damage on EAUSG. RESULTS: Five women had undergone secondary repair and three were lost to follow up. Fifty-one women (80%) completed the questionnaire. Twenty-six out of 46 (57%) of the original study group and 6/28 (20%) of the original controls were examined. Incontinence to flatus and liquid stool was more severe in the study group than in controls. Flatus incontinence was significantly more pronounced among women with subsequent vaginal deliveries. Mean maximal anal squeeze pressures were 69 mmHg in the partial rupture group and 42 mmHg in the complete rupture group (P= 0.04). Study group women with signs of internal sphincter injury reported more pronounced faecal incontinence and had lower anal resting pressures (24 mmHg) than those with intact internal sphincters (40 mmHg) (P= 0.01). Perineal body thickness of less than 10 mm was associated with incontinence for flatus and liquid stools, less lubrication during sex and lower anal squeeze pressures (58 mmHg vs 89 mmHg, P= 0.04). CONCLUSIONS: Subjective and objective anal function after anal sphincter injury deteriorates further over time and with subsequent vaginal deliveries. Thin perineal body and internal sphincter injury seem to be important for continence and anal pressure.

Adult↗

PubMed2005

Immunology of preeclampsia.

Preeclampsia is a placenta-dependent disorder with both local and systemic anomalies with neonatal and maternal morbidity. It is manifested late in pregnancy, but the onset is during early stages of gestation. The current hypothesis regarding the aetiology of preeclampsia is focused on maladaptation of immune responses and defective trophoblast invasion. Thus, an excessive maternal inflammatory response, perhaps directed against foreign fetal antigens, results in a chain of events including shallow trophoblast invasion, defective spiral artery remodelling, placental infarction and release of pro-inflammatory cytokines and placental fragments in the systemic circulation. During normal pregnancy, trophoblasts interact in the decidua with the unique uterine NK cells, modifying their cytokine repertoire, regulating adhesion molecules and matrix metalloproteinases. The inability of trophoblasts to accomplish these changes might be a critical factor for the onset of preeclampsia. Several cytokines, produced at the maternal-fetal interface, have an impact on trophoblast invasion. It is suggested that deficiency of interleukin-10 may contribute to enhanced inflammatory responses towards the trophoblasts elicited by e.g. tumour necrosis factor-alpha and interferon-gamma. Consequently, trophoblasts subjected to a high rate of apoptosis are hampered in their invasive capacity resulting in defective transformation of spiral arteries, hypoxia, thrombosis and infarction of the placenta. The ensuing infarction of placenta leads to leakage of increasing amounts of placental fragments and cytokines in the maternal circulation and an exaggerated systemic endothelial activation as identified in preeclampsia. So far, treatment of preeclampsia is focused on signs like hypertension, whereas attempts of modifying immune responses may be a possibility in the future.

Cytokines↗

PubMed2004

CYP2D6 genotypes and depressive symptoms during late pregnancy and postpartum.

The aim of this exploratory was to investigate the theory of a relation between cytochrome P450 2D6 (CYP2D6) genotype and depressive symptoms in late pregnancy and/or postpartum. We studied 145 women with depressive symptoms. CYP2D6 genotype was analysed in leukocyte DNA by polymerase chain reaction (PCR). There were no significant differences in CYP2D6 genotypes between the groups of women being depressed during and/or after pregnancy. The frequencies of CYP2D6 genotypes did not differ from other European studies. This study cannot confirm that depressive symptoms in late pregnancy and postpartum are connected with CYP2D6 genotype. It is, however, noteworthy that the frequency of ultrarapid metabolizers was higher than in a general Caucasian population. This warrants further exploration in a greater study sample, but should also be investigated in a general population with major depression.

Adult↗

PubMed2004

Eclampsia at a tertiary hospital 1973-99.

BACKGROUND: To investigate changes in incidence, patient characteristics, comorbidity and in the care provided in cases of eclampsia at a tertiary hospital during the period 1973-99. METHODS: Thirty-nine cases were identified through the Swedish National Birth Registry. Incidences and rates regarding patient characteristics and outcomes (duration of intensive care unit surveillance, assisted ventilation, multiple seizures, predefined major complications, perinatal mortality, small for gestational age, and neonatal intensive care surveillance) were compared between the time periods 1973-79, 1980-89 and 1990-99 with trend analysis. RESULTS: The incidences in the three time periods were 3.0/10,000 births [95% confidence interval (CI) 0.1-5.9], 6.2/10,000 births (95% CI 2.7-9.7) and 10.9/10,000 births (95% CI 6.4-15.4), respectively, which constitutes a significant difference according to trend analysis (p = 0.006). There were no differences in patient characteristics or comorbidity. Onset occurred in hospital in 85% of the cases. CONCLUSIONS: The increase in the incidence of eclampsia reported here is contrary to international trends up until the early 1990s. The incidence in 1990-99 is also higher than the reported national incidence in Sweden 1976-80, which was 2.9/10,000 births. Despite successful identification of women at risk for eclampsia and hospital surveillance, several cases were not prevented. Better prognostic tests that identify impending eclampsia are needed to bring the incidence down further.

Adult↗

PubMed2004

Systemic Th1/Th2 cytokine responses to paternal and vaccination antigens in preeclampsia: no differences compared with normal pregnancy.

PROBLEM: A Th1-shift has been suggested to be involved in the pathogenesis of preeclampsia. This study was designed to compare Th1/Th2 related cytokine secretion in blood between women with preeclampsia (n = 15) and normal pregnancies (n = 15), using a high-sensitivity technique for cytokine detection. METHODS OF STUDY: Spontaneous as well as 'fetus-specific' and recall antigen-specific (purified protein derivate of Mycobacterium tuberculosis, tetanus toxoid and lipopolysaccharide) secretion of interferon-gamma, interleukin (IL)-4, IL-10 and IL-12 in peripheral blood mononuclear cells (PBMC) was detected by enzyme-linked immunosorbent spot-forming cell assay (ELISPOT). Fetus-specific secretion was induced by stimulation with paternal PBMC in a mixed leukocyte culture assay. RESULTS: All cytokines were secreted by PBMCs both from women with preeclampsia and women with normal pregnancies. No differences in the number of cytokine-secreting cells were found between the two groups. CONCLUSIONS: No evidence was found for a shift in the systemic Th1/Th2 responses, in preeclampsia compared with normal pregnancy. This does, however, not exclude differences in the local immune responses related to the fetoplacental unit.

Adult↗

PubMed2003

In-situ detection of both inflammatory and anti-inflammatory cytokines in resting peripheral blood mononuclear cells during pregnancy.

INTRODUCTION: Local and possibly systemic curtailment of the maternal immune response is important for a successful pregnancy. Although the local milieu at the utero-placental interface is likely to harbor the most prominent alterations, it is suggested, at least in mice, that systemic immunity is also tolerized during pregnancy. In the present study, we investigated mRNA expression of the key immunomodulatory cytokines; interleukin (IL)-4, IL-10, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma during normal pregnancy. MATERIAL AND METHODS: In-situ hybridization (ISH) of cytokine mRNA in resting peripheral blood mononuclear cells (PBMCs) was used to detect the number of cells spontaneously expressing cytokines. Eleven women with normal gestations were followed during pregnancy as well as 8 weeks postpartum, and compared with 10 non-pregnant healthy controls. RESULTS: The numbers of IFN-gamma and IL-4 mRNA expressing cells were found to be significantly increased during pregnancy and postpartum compared with non-pregnant controls. Pregnant women and non-pregnant controls did not differ in their expression of TNF-alpha and IL-10. CONCLUSION: Our studies demonstrated increased numbers of both IFN-gamma and IL-4 mRNA expressing cells in blood suggesting that systemic immunomodulation, albeit partial, takes place during normal pregnancy. It is proposed that enhanced IL-4 expression, possibly in concert with other elevated anti-inflammatory immunomodulatory cytokines, curtail the potentially hazardous effects of IFN-gamma on systemic immunity during pregnancy.

Adult↗

PubMed2002

Obstetric, somatic, and demographic risk factors for postpartum depressive symptoms.

OBJECTIVE: To identify and test the predictive power of potential independent risk factors of postpartum depressive symptoms during pregnancy and the perinatal period. METHODS: We conducted a case-control study where 132 women with postpartum depressive symptoms were selected as an index group and 264 women without depressive symptoms as a control group. Data related to sociodemographic status, medical, gynecologic, and obstetric history, pregnancy, and perinatal events were collected from standardized medical records. RESULTS: The strongest risk factors for postpartum depressive symptoms were sick leave during pregnancy and a high number of visits to the antenatal care clinic. Complications during pregnancy, such as hyperemesis, premature contractions, and psychiatric disorder were more common in the postpartum depressed group of women. No association was found between parity, sociodemographic data, or mode of delivery and postpartum depressive symptoms. CONCLUSION: Women at risk for postpartum depression can be identified during pregnancy. The strongest risk factors, sick leave during pregnancy and many visits to the antenatal care clinic, are not etiologic and might be of either behavioral or biologic origin. The possibilities of genetic vulnerability and hormonal changes warrant further investigation to reach a more thorough understanding.

Adolescent↗

PubMed2002

Cytokine changes in postmenopausal women treated with estrogens: a placebo-controlled study.

PROBLEM: Hormone replacement therapy (HRT) is being increasingly used in postmenopausal women. Sex steroids are known to affect the immune system in several ways, although this is mainly based on clinical observations and experimental studies. METHOD OF STUDY: We studied the in vivo effects of transdermal estrogens (50 microg 17 beta-Estradiol/24 hr) on cytokine production in postmenopausal women. A total of 17 women were randomized to either placebo (n = 7) or active estrogen therapy (n = 10) for 14 weeks, with addition of oral medoxyprogesterone acetate 10 mg daily during the last 2 weeks in both groups. Secretion of the cytokines IFN-gamma, IL-4, IL-10 and IL-6 in blood mononuclear cells was determined, spontaneously and after stimulation with common vaccination antigens and mitogen, using the cell ELISA technique. RESULTS: IL-6 production after stimulation with purified protein derivate (PPD) decreased in the estrogen treated group (P < 0.01). Mitogen-induced IL-6 production was reduced in the estrogen treated group in contrast to an increase in the placebo group, leading to a significant difference (P < 0.01) between the groups after 12 weeks of treatment. This difference was eliminated after an addition of progestagens for 2 weeks. No significant changes were noted for IFN-gamma, IL-4 or IL-10 in relation to estrogen or placebo treatment. CONCLUSIONS: In the present controlled study, the main in vivo effect of estrogens was a decrease in IL-6 production, indicating a possible beneficial effect of estrogen therapy.

Cytokines↗