Charlotte A Larsson

The R28 protein of Streptococcus pyogenes is related to several group B streptococcal surface proteins, confers protective immunity and promotes binding to human epithelial cells.

The R28 protein is a surface molecule expressed by some strains of Streptococcus pyogenes (group A streptococcus). Here, we present evidence that R28 may play an important role in virulence. Sequence analysis demonstrated that R28 has an extremely repetitive sequence and can be viewed as a chimera derived from the three surface proteins Rib, α and β of the group B streptococcus (GBS). Thus, the gene encoding R28 may have originated in GBS. The R28 protein promotes adhesion to human epithelial cells, as shown by experiments with an R28‐negative mutant and by the demonstration that antibodies to highly purified R28 inhibited adhesion. In a mouse model of lethal intraperitoneal S. pyogenes infection, antibodies to R28 conferred protective immunity. However, the virulence of an R28‐negative mutant was similar to that of the parental strain in the intraperitoneal infection model. Together, these data indicate that R28 represents a novel type of adhesin expressed by S. pyogenes and that R28 may also act as a target for protective antibodies at later stages of an infection. We consider the hypothesis that R28 played a pathogenetic role in the well‐known epidemics of childbed fever (puerperal fever), which were caused by S. pyogenes. A role for R28 in these epidemics is suggested by epidemiological data.

Salivary cortisol differs with age and sex and shows inverse associations with WHR in Swedish women: a cross-sectional study

BackgroundMost studies on cortisol have focused on smaller, selected samples. We therefore aimed to sex-specifically study the diurnal cortisol pattern and explore its association with abdominal obesity in a large unselected population.MethodsIn 2001–2004, 1811 men and women (30–75 years) were randomly selected from the Vara population, south-western Sweden (81% participation rate). Of these, 1671 subjects with full information on basal morning and evening salivary cortisol and anthropometric measurements were included in this cross-sectional study. Differences between groups were examined by general linear model and by logistic and linear regression analyses.ResultsMorning and Δ-cortisol (morning – evening cortisol) were significantly higher in women than men. In both genders older age was significantly associated with higher levels of all cortisol measures, however, most consistently with evening cortisol. In women only, age-adjusted means of WHR were significantly lower in the highest compared to the lowest quartile of morning cortisol (p = 0.036) and Δ-cortisol (p < 0.001), respectively. Furthermore, when comparing WHR above and below the mean, the age-adjusted OR in women for the lowest quartile of cortisol compared to the highest was 1.5 (1.0–2.2, p = 0.058) for morning cortisol and 1.9 (1.3–2.8) for Δ-cortisol. All findings for Δ-cortisol remained after adjustments for multiple covariates and were also seen in a linear regression analysis (p = 0.003).ConclusionIn summary, our findings of generally higher cortisol levels in women than men of all ages are novel and the stronger results seen for Δ-cortisol as opposed to morning cortisol in the association with WHR emphasise the need of studying cortisol variation intra-individually. To our knowledge, the associations in this study have never before been investigated in such a large population sample of both men and women. Our results therefore offer important knowledge on the descriptive characteristics of cortisol in relation to age and gender, and on the impact that associations previously seen between cortisol and abdominal obesity in smaller, selected samples have on a population level.

Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity

OBJECTIVE The insulin responsive adiponutrin or patatin-like phospholipase 3 (PNPLA3, previously ADPN) gene shows association with obesity and in vitro adipocyte lipolysis. This study aimed to replicate the association between PNPLA3 variants and obesity, and to investigate their effect on insulin resistance and beta-cell function. METHODS rs738409 (Met148Ile) and rs2072907 (C to G) were genotyped using TaqMan allelic discrimination assay in a Swedish population-based sample (n=1811). Oral glucose tolerance test (OGTT) with data from three time points (0, 30, and 120 min) were available from individuals under the age of 50 years (n=973). RESULTS Both variant alleles were associated with decreased prevalence of obesity (P<0.05); odds ratio 0.75 (0.61-0.93) per carried Ile-allele for rs738409 and 0.80 (0.64-1.00) per carried G-allele for rs2072907. For obesity as a quantitative trait, there was no association in the whole population, but in obese subjects body mass index (BMI; P=0.023) and waist (P=0.0098) were higher in carriers of the Ile-allele. The Ile-carriers also displayed decreased insulin secretion in response to OGTT (30 min insulin; P=0.007, insulinogenic index; P=0.0051) with no significant differences in fasting plasma glucose (P=0.31), beta-cell function (disposition index; P=0.17) or homeostasis model of assessment insulin resistance (HOMA-IR; P=0.063). The correlation between BMI and HOMA-IR differed (Met/X versus Ile/Ile, P=0.028), Met-allele carriers were seemingly more insulin resistant at a lower BMI. The rs2072907 variant shows similar results for insulin secretion. The significance of this finding remained after adjusting for age, gender, and level of self-reported leisure-time physical activity. CONCLUSION We confirm the association between PNPLA3 and obesity. In addition, the rs738409 variant was associated with insulin secretion. There seems to be a differential effect of the Ile-allele depending on the degree of obesity, possibly as a consequence of insulin resistance.

Protection against experimental infection with group B streptococcus by immunization with a bivalent protein vaccine.

Group B streptococcus (GBS), a bacterium with polysaccharide capsule, is the major cause of sepsis and meningitis in early infancy. Recent work has indicated that immunity to GBS infection can be elicited by the surface proteins Rib and alpha, either of which is expressed by most GBS strains causing invasive infections. Here we show that a bivalent vaccine, composed of purified Rib and alpha mixed with aluminum hydroxide (alum), an adjuvant accepted for human use, elicits an antibody response to each of the two antigens. Moreover, the bivalent vaccine was found to protect against experimental infection with GBS strains representing the four classical serotypes. Our results represent an encouraging step towards the development of a human GBS vaccine based on pure protein antigens.

Factors Associated with Multiple Medication Use in Different Age Groups

Background: Multiple medicine use among elderly persons is likely to be the result of treatment regimens developed over a long period of time. By learning more about how multiple medication use develops, the quality of prescribing may be improved across the adult lifespan. Objective: To describe patterns of multiple medicine use in the general Swedish population and its association with sociodemographic, lifestyle, and health status factors. Methods: Data from a cross-sectional population health survey collected during 2001-2005 from 2816 randomly selected Swedish residents (age 30–75 y; response rate 76%) were analyzed. Multiple medicine use was restricted to prescription drugs and defined as the 75th percentile; that is, the 25% of the study group using the highest number of drugs per individual. Results: Seventy-one percent of the respondents used some kind of drug, 51.5% used one or more prescription drug, 38.4% used one or more over-the-counter (OTC) medication, and 8.3% used one or more herbal preparation. The cutoff amounts defining multiple medicine use were: 2 or more medications for 30- to 49-year-olds, 3 or more for 50- to 64-year-olds, and 5 or more for 65- to 75-year-olds. No association between use of multiple medicines and use of OTC drugs or herbal preparations was found. When drugs were classified into therapeutic subgroups, 76.3% of those aged 30–49 years, 97.9% of those aged 50–64 years, and 100% of those aged 65–75 years were taking a unique combination of drugs. Multivariate analyses showed that diabetes and poor self-rated health were associated with multiple medicine use in all age cohorts. Female sex and hypertension were associated with multiple medicine use among those aged 30–49 and 50–64 years, current smoking among those aged 50–64 years, and obesity among those aged 65–75 years. Conclusions: Multiple medicine use was associated with morbidity and poor self-rated health across all age groups. The vast majority of users of multiple drugs are taking a unique combination of medications.

Sexual and gender-related harassment in medical education and research training: results from a Swedish survey.

Objective  The aims of this study were to establish the level of perceived sexual and gender‐related harassment in undergraduate and doctoral studies, in which environment the events occurred, which categories of persons had committed the harassment, and other aspects of sexual harassment at the Faculty of Medicine, Gothenburg University.

Cross-Protection between Group A and Group B Streptococci Due to Cross-Reacting Surface Proteins

The R28 protein of group A streptococcus (GAS) and the Rib protein of group B streptococcus (GBS) are surface molecules that elicit protective immunity to experimental infection. These proteins are members of the same family and cross-react immunologically. In spite of extensive amino acid residue identity, the cross-reactivity between R28 and Rib was found to be limited, as shown by analysis with highly purified proteins and specific antisera. Nevertheless, immunization of mice with purified R28 conferred protection against lethal infection with Rib-expressing GBS strains, and immunization with Rib conferred protection against R28-expressing GAS. Thus, R28 and Rib elicited cross-protective immunity. Characterization of many clinical GAS and GBS isolates expressing R28 or Rib, respectively, indicated that most of them expressed proteins similar to those of the reference strains. Analysis of these data suggests that cross-protection may influence the outcome of natural infections with R28-expressing GAS and Rib-expressing GBS.

Leisure time and occupational physical activity in relation to obesity and insulin resistance: a population-based study from the Skaraborg Project in Sweden

The objective was to study obesity and insulin resistance in relation to leisure time physical activity (LTPA) and occupational physical activity (OPA) in a Swedish population, with particular focus on sex differences. Using a cross-sectional design, waist circumference, body mass index (BMI), glucose/insulin metabolism, blood pressure, heart rate, self-reported education, smoking, alcohol consumption, LTPA, and OPA were assessed in 1745 men and women (30-74 years) randomly chosen from 2 municipalities in southwestern Sweden. In both men and women, LTPA was inversely associated with BMI, waist circumference, and the homeostasis model assessment of insulin resistance (HOMA-IR), respectively. These associations remained statistically significant after adjustments for age, OPA, education, alcohol consumption, smoking, and study area, and also for BMI in the analyses concerning waist circumference and HOMA-IR. A statistically significant interaction term (P = .030), adjusted for multiple confounders, revealed a stronger association between LTPA and HOMA-IR in women compared with men. Occupational physical activity was positively associated with BMI (P < .001), waist circumference (P < .001), and HOMA-IR (P = .001), however, only in women. These associations remained when adjusting for multiple confounders. The sex differences were confirmed by statistically significant interaction terms between sex and OPA in association with BMI, waist circumference, and HOMA-IR, respectively. The observed sex differences regarding the strength of the association between LTPA and insulin resistance, and the positive association between OPA and obesity and insulin resistance found solely in women, warrant further investigation. Although exploration of the metabolic effects of OPA appears to be needed, thorough measurement of potential confounders is also vital to understand contextual effects.

C-peptide: New findings and therapeutic possibilities

Much new information on C-peptide physiology has appeared during the past 20 years. It has been shown that C-peptide binds specifically to cell membranes, elicits intracellular signaling via G-protein and Ca2+ -dependent pathways, resulting in activation and increased expression of endothelial nitric oxide synthase, Na+, K+ -ATPase and several transcription factors of importance for anti-inflammatory, anti-oxidant and cell protective mechanisms. Studies in animal models of diabetes and early clinical trials in patients with type 1 diabetes demonstrate that C-peptide in replacement doses elicits beneficial effects on early stages of diabetes-induced functional and structural abnormalities of the peripheral nerves, the kidneys and the retina. Much remains to be learned about C-peptides mechanism of action and long-term clinical trials in type 1 diabetes subjects will be required to determine C-peptides clinical utility. Nevertheless, even a cautious evaluation of the available evidence presents the picture of a bioactive endogenous peptide with therapeutic potential.

Prevalence, awareness, treatment, and control of hypertension: Rule of thirds in the Skaraborg project

Abstract Objective. To describe the prevalence, awareness, and control of hypertension in a Swedish population during the early 2000s to address implications for care and prevention. Design. A cross-sectional population survey. Setting. Primary health care in Skaraborg, a rural part of western Sweden. Subjects. Participants (n =2816) in a population survey of a random sample of men and women between 30 and 75 years of age in the municipalities of Vara (81% participation rate) and Skövde (70%), in western Sweden during 2001–2005. Main outcome measures. Anthropometric measures, blood pressure, leisure-time physical activity, current smoking, fasting glucose, and cholesterol. Hypertension was defined as ongoing treatment for hypertension, or three consecutive blood pressure readings ≥140 systolic and/or ≥90 mmHg diastolic. Hypertension was considered controlled when the blood pressure was <140/90 mm Hg (both). Results. The prevalence of hypertension was 20% in both men and women with a steep increase by age. Among hypertensive subjects, 33% were unaware, 36% aware but uncontrolled, and 31% aware and controlled, with no statistically significant differences between men and women. Patients with diabetes had a higher awareness (87% vs. 64%, p <0.001), but the same control rate (56% vs. 44%, p =0.133), when compared with those without diabetes. Conclusion. A large proportion of subjects with hypertension are still unaware of their condition, or aware but not controlled. It is important to emphasize population-based prevention to reduce the prevalence of hypertension, to perform screening to increase awareness, and to improve implementation of expert guidelines in clinical practice to improve control.