Search PubMed⌕ Search

Biomedical subjects

C Magnusson

Publications and source records attributed to C Magnusson.

At least 37 records · Page 2Linked to original sources

Signalling by CD95 and TNF receptors: not only life and death.

Members of the TNF family of receptors play important roles in normal physiology and in defence. The recent rapid progress in the understanding of the mechanisms of apoptosis has been accompanied by assumptions that TNF family receptors such as CD95(Fas/APO-1) only have a role in regulating cell survival. While regulation of cell death is one important function of TNF family receptors, they are capable of activating signal transduction pathways that have many other effects. The present review will focus on signalling of some TNF family receptors in the immune system, not only for apoptosis, but also for survival or activation.

Animals↗

Hormone replacement therapy and risk of hip fracture: population based case-control study. The Swedish Hip Fracture Study Group.

OBJECTIVE: To determine the relative risk of hip fracture associated with postmenopausal hormone replacement therapy including the effect of duration and recency of treatment, the addition of progestins, route of administration, and dose. DESIGN: Population based case-control study. SETTING: Six counties in Sweden. SUBJECTS: 1327 women aged 50-81 years with hip fracture and 3262 randomly selected controls. MAIN OUTCOME MEASURE: Use of hormone replacement therapy. RESULTS: Compared with women who had never used hormone replacement therapy, current users had an odds ratio of 0.35 (95 % confidence interval 0.24 to 0.53) for hip fracture and former users had an odds ratio of 0.76 (0.57 to 1.01). For every year of therapy, the overall risk decreased by 6% (3% to 9%): 4% (1% to 8%) for regimens without progestin and 11% (6% to 16%) for those with progestin. Last use between one and five years previously, with a duration of use more than five years, was associated with an odds ratio of 0.27 (0.08 to 0.94). After five years without hormone replacement therapy the protective effect was substantially diminished (-7% to 48%). With current use, an initiation of therapy nine or more years after the menopause gave equally strong reduction in risk for hip fracture as an earlier start. Oestrogen treatment with skin patches gave similar risk estimates as oral regimens. CONCLUSIONS: Recent use of hormone replacement therapy is required for optimum fracture protection, but therapy can be started several years after the menopause. The protective effect increases with duration of use, and an oestrogen-sparing effect is achieved when progestins are included in the regimen.

Administration, Cutaneous↗

Body size in different periods of life and breast cancer risk in post-menopausal women.

Adult obesity has been associated with an increased risk of post-menopausal breast cancer, but it is unclear whether this relationship reflects a causal role of obesity during childhood and adolescence, of weight gain during adult life or of adult obesity per se. In a population-based case-control study in all of Sweden, we included 3,345 (84% of all eligible) women aged 50-74 years with invasive breast cancer, and 3,454 (82% of all selected) controls of similar age. Mailed questionnaires and telephone interviews were used to collect detailed information on anthropometric measures. Odds ratios were estimated through multiple logistic regression. Women with the leanest somatotype at age 7 had about a 3-fold higher risk of breast cancer than the most obese (P for trend 0.0009). A suggested protective effect of a high body mass at age 18 and a detrimental influence of body mass 1 year prior to data collection largely reflected the effect of weight gain after age 18, a strong predictor of breast cancer risk. Among women at least 20 years post menopause, those who had gained 30 kg or more since age 18 had an odds ratio of 2.04 (95% confidence interval 1.20-3.48) of breast cancer compared with those who had maintained their weight unchanged. The effect of weight gain was unequivocal among non-users but not among users of hormone replacement therapy. Our findings have important implications, suggesting weight preservation as a means for prevention of post-menopausal breast cancer as well as a causal role of childhood body build in breast cancer etiology.

Age Factors↗

Association of family history and other risk factors with breast cancer risk (Sweden).

OBJECTIVES: Women with a family history of breast cancer have an increased risk for the disease. However, the combined impact of family history and other risk factors on breast cancer risk is unclear. We conducted a large epidemiologic study to examine this issue. METHODS. In a population-based case-control study in all of Sweden, 3,345 women aged 50 to 74 years with invasive breast cancer (84 percent of all eligible), and 3,454 controls of similar age (82 percent of all selected) were included. Mailed questionnaires and telephone interviews were used to collect detailed information on potential breast cancer risk factors. Odds ratios (OR) and 95 percent confidence intervals (CI) were estimated through multiple logistic regression. RESULTS: Women with a history of breast cancer in any first-degree relative had an increased risk of breast cancer compared with those without such a history (OR = 1.96, CI = 1.67-2.30). There was no clear indication of a differential impact of hormonal risk factors (age at menarche, parity, age at first birth, age at menopause, use of exogenous hormones, and weight gain) or body build at age seven among women with and without a positive family history. Yet, benign breast disease and height clearly were related to breast cancer risk in subjects without a family history, whereas seemingly not so in women with a family history. Formal tests for interaction between family history and these factors, however, did not prove statistically significant. CONCLUSIONS: Our findings indicate that established risk factors entail similar associations with breast cancer risk among women with and without family history of the disease.

Aged↗

A follow-up study of adolescent girls with early sexual debut in combination with gynecological problems.

This research examined the extent to which women's reproductive experiences during adolescence have repercussions in adult life with regard to sexuality, self-image and state of gynecological health. The investigated group comprised 30 females (study group), with a sexual debut at the age of 15 years or younger and documented gynecological ill-health during adolescence. A comparison was made with 30 matched females from the same school classes (control group) without documented gynecological ill-health. At the age of 25-30 a semi-structured interview was conducted with both investigated and control participants. The majority of the women from the study group experienced their adolescent sexual experiences as generally negative. In early adulthood these women had more recurrent and varied gynecological illnesses than their control group counterparts. The study group women more often referred to their appearance as an indicator of their femininity than did the control women (who defined femininity in terms of 'to be in a relationship'). The study group women had a more negative attitude towards their own body than did the control women. Study group women's early sexual experience was also linked to an increase in norm-breaking behavior, lower educational attainment and a younger age of adult responsibilities compared with the control women.

Adolescent↗

Prognostic characteristics in breast cancers after hormone replacement therapy.

We examined the influence of hormone replacement therapy (HRT) on breast tumour biology by comparing the prognostic characteristics of breast cancers and survival in 121 women prescribed replacement hormones before diagnosis with those in 1468 women without such treatment. The women receiving HRT had a lowered relative risk of being diagnosed with tumours of more than 20 mm in diameter, OR = 0.7 (CI 0.5-1.0) and axillary lymph node dissemination, OR = 0.7 (CI 0.4-1.1). These risk reductions were most pronounced and statistically significant in the women who had been prescribed a combined estradiol-progestin regimen. The patients in this compound group also had a diminished relative risk of having poorly differentiated tumours. Further, there was an indication that the women prescribed HRT, and especially those with conjugated estrogens/estradiols alone, had a decreased relative risk of developing aneuploid tumours. There was no clear pattern for women receiving the biologically weak oestriol, although risk estimates were generally higher for unfavourable tumours in comparison with those receiving the higher potency compounds. Adjustments for indications of earlier detection (i.e. lead time bias) did not influence the pattern or magnitude of the risk estimates. No association between any type of HRT and survival after breast cancer diagnosis was noted, but analyses were based only on 19 breast cancer deaths among exposed patients. We conclude that breast cancers occurring after treatment with HRT, especially the combined estrogen-progestin regimen, seem to have more favourable tumour features than tumours in non-treated women. Our findings may reflect a less aggressive biological behaviour of breast cancers in women receiving HRT, or in part be explained by the earlier detection of the tumours in these women.

Aged↗

Life with Turner's syndrome--a psychosocial report from 22 middle-aged women.

Twenty-two middle-aged women (median age 44.5 years) with Turner's syndrome were interviewed about family background, social identity, emotional development, relations, female identity, sexuality and reactions to the diagnosis, to evaluate how the condition has affected their lives and coping style. During the years preceding the diagnosis and hormonal replacement therapy (HRT) they had often isolated themselves as they felt different from their peers. Ovarian failure and infertility, not the body height, were the major problems for most of the women. Infertility had affected the women very deeply and many felt depressed because of this. Adolescent behaviour, a feeling of chronic inferiority or a feeling of grief were different ways of coping with the situation. Median age at sexual debut was 19.5 years. Painful intercourse related to vaginal constriction and sore membranes was commonly reported. Most of the women had stopped HRT because of side-effects. Many of the problems experienced by the women could have been avoided if proper HRT had been administered in due time and on a long-term basis. This emphasizes the importance of regular contact with a gynecologist of special training and interest.

Adaptation, Psychological↗

Psychosocial impact of persistent trophoblastic disease.

The female identity of women who suffer from hydatidiform mole developing into persistent trophoblastic disease is threatened in two ways. The reproductive failure is shortly followed by a disease originating in the uterus requiring chemotherapy. Although somatic treatment results are excellent, the psychological effects may be severe and protracted. We conducted a study of 22 women who were between 6 months and 5 years after the end of successful treatment. It appeared that 19 women suffered from psychological sequelae. The three oldest women of the study group, 50 years or older, belonged to the group of women demonstrating signs of prolonged psychological effects.

Adaptation, Psychological↗

Lead given systemically to mice in experimental delay of implantation increases the oxygen consumption of delayed blastocysts.

The metabolic activity of pre-implantation blastocysts recovered from delayed mice before and after administration of lead was estimated by measuring their oxygen consumption using a spectrophotometer technique. Normal blastocysts, activated for implantation, increased their oxygen consumption by about 50% compared with inactive, delayed blastocysts. Inactive, delayed blastocysts from lead-injected mice reached the same level of oxygen consumption even without oestrogen administration. Oestrogen given to the lead-injected mice did not further increase the oxygen consumption of their blastocysts. It is concluded that administration of lead to pre-implantation mice resulted in increased metabolic activity of their blastocysts due either to a direct effect of lead or to an indirect effect, caused by changed composition of the uterine secretion.

Animals↗

Epithelial transport of drugs in cell culture. II: Effect of extracellular calcium concentration on the paracellular transport of drugs of different lipophilicities across monolayers of intestinal epithelial (Caco-2) cells.

A human intestinal cell line, Caco-2, was used as a model to study the passive diffusion of a homologous series of drugs (beta-blocking agents) of different lipophilicity across intestinal epithelium. The permeability of the Caco-2 monolayers was modulated by the use of a calcium switch assay. The transmembrane resistance could be reversibly decreased from approximately 280 ohms.cm2 (a resistance similar to that of colon epithelium) to approximately 60 ohms.cm2 (a resistance similar to that of small intestine epithelium). Transmission electron microscopy showed that the increased electrical permeability was caused by a reversible separation of the components of the junctional complex and not by cell detachment. In general, the increased paracellular permeability resulted in a 2- to 9-fold increase in the apparent permeability coefficients for the more hydrophilic drugs (e.g., from 0.20 +/- 0.010 x 10(-6) to 1.43 +/- 0.185 x 10(-6) cm/s for atenolol), while the transport parameters for the more lipophilic drugs remained unchanged (e.g., 43.03 +/- 3.64 x 10(-6) and 46.10 +/- 3.25 x 10(-6) cm/s for propranolol). These findings indicate that it is possible to study the contribution of the paracellular pathway to the transport of drugs in the Caco-2 model.

Calcium↗

Effects of follicle stimulating hormone and purines on rat oocyte maturation.

The presented data demonstrate a dose-dependent inhibition of spontaneous meiosis of cumulus-enclosed rat oocytes by guanosine, hypoxanthine, and adenosine. The inhibition by adenosine was transient whereas guanosine and hypoxanthine exerted a persistent effect over 24 h of incubation. The order of potency of the substances was guanosine greater than hypoxanthine greater than adenosine and the inhibition was reversible. The inhibitory effect was reduced when the cumulus cells around the oocyte were removed. The inhibition during the first 12 h of incubation was potentiated by FSH. However, at 24 h of incubation FSH partially overcame the inhibitory effect by hypoxanthine but did not influence the inhibitory effect by guanosine. Also 8BrcAMP potentiated the inhibitory effect observed by guanosine, hypoxanthine, and adenosine, suggesting that the potentiating effect of FSH was mediated via cAMP. Our data demonstrate that adenosine, hypoxanthine, and guanosine synergized with FSH in inhibiting spontaneous rat meiosis, as previously shown in mouse. FSH could partially overcome the inhibitory effect exerted by hypoxanthine but did not counteract the inhibitory effect of guanosine.

Adenosine↗

Interleukin 4 induces synthesis of IgE and IgG4 in human B cells.

Interleukin (IL)4 has been shown to regulate the IgG subclasses and induce IgE production in splenic mouse B cells. Here we show that IL4 and phorbol 12-myristate 13-acetate (PMA) induce, on a per cell basis, very high IgE secretion in purified human B cells by using a mouse thymoma (EL4) co-culture method. In addition, a marked increase in the number of IgG4-producing cells was also observed. Furthermore, IL2 could synergize with IL4 and PMA in the production of IgE. By using limiting dilution analysis, a considerable increase in the precursor frequency for IgE was found when IL4 and PMA were added to cultures as compared to cultures with PMA only. This indicates that IL4 induces an isotype switch in human B cells.

Antibody Formation↗

Effects of metabolic inhibitors on hormone release, cyclic AMP levels, and oxygen consumption in rat pituitary cells in culture.

The metabolic inhibitors antimycin A (2 mumol/l), dinitrophenol (0.5 mmol/l), and iodoacetate (6 mmol/l) were tested for their effects on hormone release, cAMP levels, and oxygen consumption in clonal strains of rat pituitary cells (GH3 cells). Basal release of growth hormone (GH) and prolactin (PRL) was reduced by all three inhibitors, and thyrotropin-releasing hormone (TRH) (1 mumol/l) and K+ (50 mmol/l) stimulated hormone release were blocked. Trifluoperazine, a calmodulin antagonist, inhibited basal GH and PRL release at concentrations up to 30 mumol/l and stimulated above 50 mumol/l. The stimulatory effect of 80 mumol/l trifluoperazine on basal hormone release was eliminated by antimycin A, dinitrophenol, and iodoacetate, whereas the inhibitory effect of antimycin A, dinitrophenol and iodoacetate on basal hormone was not affected by 30 mumol/l trifluoperazine. None of the inhibitors had any effect on the level of cellular cAMP (i.e. intracellular plus extracellular). Oxygen consumption of GH3 cells was blocked by antimycin A, reduced by 25% by iodoacetate and increased by about 100% by dinitrophenol. In contrast, hormone secretion stimulated by TRH and K+ was not accompanied by any measurable alteration in oxygen consumption. Trifluoperazine (greater than or equal to 80 mumol/l) reduced the basal oxygen consumption and blocked the stimulatory effect of dinitrophenol on oxygen consumption. In conclusion, inhibition of the energy generation of GH and PRL-producing cells severely affects the action of secretagogues, although stimulated hormone secretion may not be accompanied by any measurable increase in oxygen consumption. The cellular energy supporting hormone secretion is mostly generated via oxidative phosphorylation.

Animals↗

Studies on microbial contamination of reused disposable plastic insulin syringes.

The microbial contamination of reused disposable insulin syringes and bottles was studied. Fourteen patients, aged 16-64 years, took part in the study. 50 syringes and 52 bottles were examined for sterility at different stages of use. Twelve (24%) syringes and 4 (8%) bottles were found to be contaminated by micro-organisms, although only in low numbers. The micro-organisms recovered belonged to the normal skin flora of man.

Adolescent↗

Oxygen consumption by human oocytes and blastocysts grown in vitro.

Oxygen consumption by human oocytes and blastocysts was analysed using a sensitive micro-spectrophotometric technique. Oocytes were obtained from women undergoing laparotomy for sterilization or hysterectomy, and blastocysts were obtained as spare embryos from the local in-vitro fertilization programme. There was no significant difference between oocyte oxygen consumption on the day of isolation and after 1 day of culture, 0.53 +/- 0.08 (n = 9) and 0.35 +/- 0.06 (n = 5) nl/h oocyte, respectively. Blastocyst oxygen consumption was measured after a culture period of 5-8 days after in-vitro fertilization. Mean oxygen consumption by healthy looking blastocysts was 0.34 +/- 0.03 (n = 15) nl/h blastocyst, and there was no change in oxygen consumption with culture time. This level of respiration was lower than expected, both when compared with the oocytes and when compared with levels reported for blastocysts of other species.

Blastocyst↗