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Biomedical subjects

I Larsson

Publications and source records attributed to I Larsson.

At least 19 recordsLinked to original sources
PubMed2007

Increased cystatin C expression in the pre-eclamptic placenta.

Trophoblast invasion is regulated by proteinases and their inhibitors. Cystatin C inhibits cysteine proteinases. The serum concentration of cystatin C is increased in late pregnancy and pre-eclampsia. We aimed to investigate whether the expression of cystatin C is increased in the pre-eclamptic placenta and to investigate the expression pattern of cystatin C mRNA and protein in placental tissue. Tissue samples from the central part of the placenta from 13 normal and 22 pre-eclamptic pregnancies were included. We used real-time polymerase chain reaction (RT-PCR) and in situ hybridization for mRNA expression analysis and immunohistochemistry and Western blotting for protein expression analysis. RT-PCR showed a significantly higher expression of cystatin C mRNA in pre-eclampsia than in normal pregnancy, with the highest expression in cases with severe pre-eclampsia. In situ hybridization revealed a distinct pattern of high expression in the extravillous trophoblast cells of the basal plate and low expression in the syncytiotrophoblast covering villi. The cystatin C protein distribution matched the mRNA expression pattern. Western blot analysis revealed an increased protein expression in cases with severe pre-eclampsia and confirmed the presence of cystatin C in amniotic fluid samples. The high expression of cystatin C mRNA in the extravillous trophoblast cells of the basal plate suggests a role for cystatin C in the regulation of proteases in placentation. Placental expression and secretion of cystatin C could contribute to the elevated maternal plasma levels seen in pre-eclampsia.

Adult↗
PubMed2006

Gene expression profiling of human placentas from preeclamptic and normotensive pregnancies.

The aim of this study was to investigate patterns of gene expression in placental samples from patients with preeclampsia (PE), persistent bilateral uterine artery notching (without PE), and normal controls. This study included placental tissue from nine women with PE, seven with uncomplicated pregnancies and five with bilateral uterine artery notching in Doppler velocimetry tracings. Human cDNA microarrays with 6500 transcripts/genes were used and the results verified with real-time PCR and in-situ hybridization. Multidimensional scaling method and random permutation technique demonstrated significant differences among the three groups examined. Within the 6.5K arrays, 6198 elements were unique cDNA clones representing 5952 unique UniGenes and 5695 unique LocusLinks. Multidimensional scaling plots showed 5000 genes that met our quality criteria; among these, 366 genes were significantly different in at least one comparison. Differences in three genes of interest were confirmed with real-time PCR and in-situ hybridization; acid phosphatase 5 was shown to be overexpressed in PE samples and calmodulin 2 and v-rel reticuloendotheliosis viral oncogene homolog A (RELA) were downregulated in PE and uterine artery notch placentas. In conclusion downregulation of RELA and calmodulin 2 might represent an attempt by the placenta to compensate for elevations in intracellular calcium, possibly caused by hypoxia and/or apoptosis, in both pregnancies with uterine artery notching and preeclampsia.

Adult↗
PubMed2004

Norepinephrine transporter (NET), serotonin transporter (SERT), vesicular monoamine transporter (VMAT2) and organic cation transporters (OCT1, 2 and EMT) in human placenta from pre-eclamptic and normotensive pregnancies.

Pre-eclampsia is one of the most common causes of perinatal and maternal morbidity and mortality. High blood pressure and proteinuria are important clinical signs of pre-eclampsia. Sympathetic overactivity and elevated level of circulating vaso active substances, such as monoamines has been shown. Extracellular concentrations of monoamines are normally kept low by specific transporter proteins of which many are expressed in the placenta. In this study we used in situ hybridization and real-time PCR to study the gene expression of monoamine transporters, such as NET, SERT, VMAT2, EMT and OCT1/2, in normal as well as in pre-eclamptic placentae. We demonstrated high expression of NET mRNA in the trophoblast cells of the anchoring villi and a lower expression intensity in the chorionic villi. SERT mRNA was mainly detected in chorionic villi. VMAT2 mRNA was not detected in the central part of the placenta but was present in the spiral arteries of placenta bed biopsies, in cytokeratin positive cells. EMT mRNA was mainly detected in the intra lobular septa and together with OCT1 and OCT2 mRNAs also expressed in scattered cells of placental vessel adventitias. Moreover, quantitative analysis showed a significant lower expression of NET and EMT mRNAs in pre-eclamptic placentae as compared to the control group. A defective gene expression or function of these monoamines transporters might explain the elevated concentrations of monoamines in pre-eclamptic patients. Monoamine transporters may serve as a protective mechanism preventing vasoconstriction in the placental vascular bed and thereby securing a stable blood flow to the fetus.

Adult↗
PubMed2004

Body composition in the SOS (Swedish Obese Subjects) reference study.

OBJECTIVE: The primary objective was to establish population-based, sex- and age-specific reference data with respect to body composition variables. Secondary objectives were to relate body mass index (BMI) to anthropometric measurements reflecting central adiposity and to body fat (BF). Another objective was to examine if secular changes in adipose tissue distribution occurred during the sampling period, 1994-1999. DESIGN: Sex- and age-specific data on anthropometric measurements and body composition were cross-sectionally collected in the reference study of Swedish Obese Subjects. SUBJECTS: In total, 1135 randomly selected subjects (524 men and 611 women), aged 37-61 y, BMI 17.6-45.4 kg/m(2). MEASUREMENTS: Measures of body fatness and fat distribution (by dual energy X-ray absorptiometry and anthropometry) were collected. RESULTS: At BMI 25 kg/m(2), relative (absolute) BF mass was 24% (19 kg) in men vs 36% (25 kg) in women, waist circumference was 90 vs 85 cm, and sagittal trunk diameter was 21 vs 19 cm. BF and measures of centralized adipose tissue distribution increased with age in both sexes (P<0.01). In women, waist circumference and sagittal diameter increased (P<0.01) over the sampling period while BMI did not. CONCLUSIONS: Sex- and age-specific reference data on body composition are reported from a randomly selected sample of Swedish men and women. At given BMIs, women had more BF but smaller waist circumference than men. Secular increases in indices of central obesity were found in women but not in men.

Absorptiometry, Photon↗
PubMed2003

Important differences in nitric oxide synthase activity and predominant isoform in reproductive tissues from human and rat.

For the extrapolation of data obtained from experimental animals to the human situation, it is important to know the similarities and differences between human and animal species. Some important characteristics of nitric oxide synthase (NOS) in myometrium and vagina from human and rat were compared. NOS-activity was measured by the formation of 14C-citrulline from 14C-arginine and the expression of NOS isoforms was examined by Western blotting. NOS activity in human uterus and vagina was significantly lower than in the tissues from rat. In contrast to the rat where NOS activity was predominantly found in the cytosolic fractions, NOS activity in particulate and cytosolic fractions from both human myometrium and vagina was similar. Data from Western blots confirmed that eNOS and nNOS isoforms were concentrated in the particulate and cytosolic fractions, respectively. Estrogen treatment of rats resulted in a down regulation of uterine cytosolic NOS activity. A down regulation of NOS in the cytosolic fraction was also seen in the human pregnant myometrium as compared with the nonpregnant myometrium. The vaginal NOS activity was considerably higher than the uterus in both species. In spite of some clear-cut qualitative and other differences between human and rat tissues, there are some interesting similarities. Downregulation in pregnancy of human uterine NOS is probably due to, at least in part, the influence of estrogen and progesterone.

Adult↗
PubMed2001

Effect of ovarian steroids on nitric oxide synthase in the rat uterus, cervix and vagina.

The effects of estrogen (E2), progesterone (P) and E2 and P (E2 + P) were examined on nitric oxide synthase (NOS) activity in both cytosolic and particulate fractions isolated from the rat uterus, vagina, cervix and cerebral cortex. Additionally plasma nitrate + nitrite (NO3 + NO2) levels were measured in control and hormone treated rats. Cytosolic NOS was the predominant form being approximately 80% of the total in all four tissues. NOS activity in both fractions from all tissues was highly Ca-dependent (> 90%). Among the reproductive tract tissues, the highest activity was found in the cervix, which was nearly 5- and 2-fold higher than the uterus and vagina, respectively. NOS activity in the cerebral cortex was by far the highest being 5-fold higher than in the cervix. In contrast to the cortex, E2 treatment downregulated cytosolic NOS in all reproductive tract tissue, but this was statistically significant in only uterus. When compared with E2 treated rats, P increased cytosolic NOS in uterus, vagina, and particulate NOS in the cervix. The data do not give any indication whatsoever of differential effects of P in the uterus and cervix.

Animals↗
PubMed2001

Paranasal sinus ventilation in healthy subjects and in patients with sinus disease evaluated with the 133-xenon washout technique.

Ventilation of the paranasal sinuses is of great importance in sinus pathophysiology. Therefore, methods of measuring sinus ventilation are important for the evaluation of patients with sinus disease. In the present study, a 133-xenon washout technique was used to evaluate the ventilation of the paranasal sinuses in 34 healthy subjects and in 13 subjects with sinus disease (5 patients with nasal polyposis and 8 patients with chronic sinusitis). For this purpose, a 133-xenon-air mixture was insufflated in each nostril and the washout of the radioactive gas from the paranasal sinuses was monitored with a dynamic single-photon-emission computed tomography camera. The half-time (+/-SD) was found to be 18 +/- 18 minutes for the maxillary sinus, 10 +/- 8 minutes for the frontal sinus, and 18 +/- 23 minutes for the posterior ethmoid and sphenoid sinuses in the healthy subjects. Repeated measurements in 18 of the healthy subjects indicated that the method had acceptable reproducibility according to a Bland-Altman plot. The 133-xenon washout was not influenced by insufflation pressure, nasal patency, or body position. The subjects with sinus disease exhibited half-times of 77 +/- 101 minutes for the maxillary sinus, 91 +/- 124 minutes for the frontal sinus, and 60 +/- 60 minutes for the posterior ethmoid and sphenoid sinuses. For patients with nasal polyposis, the half-time was significantly longer than that in healthy subjects, while patients with chronic sinusitis did not differ from healthy subjects in this respect.

Adolescent↗
PubMed2001

Sexual behaviour in Swedish preschool children, as observed by their parents.

UNLABELLED: Issues of what constitutes normal and healthy childhood sexual behaviour have acquired new implications in the light of child sexual abuse. Increased knowledge in this area is therefore of vital importance and studies in different countries are needed. In the present study parents of 231 children aged 3-6 y were asked to answer questionnaires about their child's behaviour at home. The questionnaire consisted of four sections: demographic data, a general behaviour checklist, a sexual behaviour inventory, and attitudinal questions to the parents. The results showed that children in Sweden exhibit a wide range of sexual behaviour, most of them developmentally related. Some behaviour appeared to be very rare in a normative sample of preschool children and included behaviours usually referred to as sexualized and problematic. Reports on sexual behaviour in the children were also related to general behaviour reports, the parent's socioeconomic level, parental attitudes towards child sexuality and the openness of family habits. CONCLUSION: There is a need for further national studies in different settings, to help create a better understanding of what constitutes both normative and deviant sexual behaviour in children.

Child↗
PubMed2000

Mitochondrial and microsomal peripheral benzodiazepine receptors in human ovarian cancer xenografts.

To investigate whether the density of peripheral benzodiazepine receptors (PBR) in human ovarian tumors is related to the degree of histological differentiation and possibly elucidate their pathophysiology, PBR were measured in mitochondrial (m) and microsomal (p) fractions isolated from six different human ovarian carcinomas heterotransplanted into nude mice. A specific ligand PK11195 for PBR was employed and the density of binding sites and binding affinity (KD) were computed from Scatchard analysis. The PBR density in m-fractions was 3- to 4-fold higher than in p-fractions from all tumors. PBR density in both m- and p-fractions was highest in mucinous tumors with mid-high degree of differentiation. The density in serous tumor with mid-high differentiation was significantly lower than the mucinous tumor, but higher than the serous tumor with low degree of differentiation (OVCAR-3) in both m- and p-fractions. However, the PBR density in the undifferentiated tumor (IGROV1) was higher than in OVCAR-3. The KD values for PBR were very low ranging from 5.8 to 14.0 nM in all preparations. The KD values for p-fractions were generally lower than m-fractions and highly significant differences were observed in three of the six tumors. These data suggest two separate classes of PBR pertaining to m- and p-fractions and indicate that there is no clear relationship between PBR density and degree of differentiation.

Animals↗
PubMed1999

The 'Green Keyhole' revisited: nutritional knowledge may influence food selection.

INTRODUCTION: The food-marking symbol the 'Green Keyhole' has been in use since 1989 in Sweden, to make it easier for consumers to select low-fat and high-fibre alternatives. OBJECTIVE: To describe knowledge of the Green Keyhole symbol in a general population of both sexes and the association between knowledge and intake of Green Keyhole labelled foods. DESIGN: A cross-sectional study within the GOT-MONICA project 1995/96. SUBJECTS: 732 males and 859 females, aged 25-64 y. METHODS: Reported intakes of Green Keyhole labelled low-fat and fibre-enriched foods from a food frequency questionnaire, in relation to knowledge of the Green Keyhole symbol. RESULTS: 53% and 76% of the males and females, respectively, understood the meaning of the symbol. SUBJECTS with knowledge were significantly younger (P<0.0001) and (among women) thinner (P=0.0105), than those without knowledge. Intakes of Green Keyhole labelled low-fat foods were significantly higher in males (P=0.0443) and females (P<0.0001) with knowledge of the symbol than without. An interaction between education and knowledge of the Green Keyhole symbol was found for intake of low-fat marked foods (P=0.0088). CONCLUSIONS: Both males and females with knowledge of the symbol seem to have adopted its low-fat message. However, in certain sub-groups, particularly the less educated, the message of the symbol appears to have no association with dietary practices.

Adult↗
PubMed1997

Bridging the gap: support groups do not enhance long-term outcome in chronic back pain.

OBJECTIVE: Because back pain patients often relapse within months of treatment, the effects of two types of support groups as a complement to usual medical treatment was investigated on long-term outcome. DESIGN: Regular treatment was compared with an "educational" support group and a professional support group before and 1 year after intervention in a randomized controlled trial. PATIENTS: A total of 76 women and 27 men, average age of 50 years and with an accumulated sick leave for musculoskeletal pain of 2-24 weeks during the past year, were randomly assigned to the three groups. OUTCOME MEASURES: Sick leave records were obtained from the National Insurance Authority. A battery of standardized instruments was employed, which featured the Sickness Impact Profile, the Coping Strategies Questionnaire, the Multidimensional Pain Inventory, the Pain and Impairment Relationship Scale, the Pain and Discomfort Scale, the Pain Beliefs and Perceptions Inventory, and the Outcome Evaluation Questionnaire. RESULTS: The Educational Support Group demonstrated greater attendance than did the Professional Support Group. However, long-term outcome was not significantly different between any of the groups for sick leave, coping, function, or experienced pain. Both support groups, relative to the Regular Treatment Group, made greater improvements on the Sickness Impact Profile. CONCLUSION: This study provides little evidence that support groups, as a complement to regular treatment, enhance long-term outcome for subacute musculoskeletal pain problems. Specific treatment techniques, matched to the patient's needs, stringently taught, and delivered in a more compact form, may be necessary for enhancing outcome.

Adolescent↗
PubMed1996

Cloning of beta-microseminoprotein of the rat: a rapidly evolving mucosal surface protein.

beta-Microseminoprotein is a small, nonglycosylated protein, rich in disulfide bonds, which is present in the secretions of the airways, the gastrointestinal tract, and the urogenital tract. Its function is unknown. It was originally characterized in the human and it has been difficult to identify the homologous protein in species other than primates. We have purified beta-microseminoprotein from rat prostate and from amino acid sequencing we have been able to clone the protein. The results reinforce conclusions reached earlier that beta-microseminoprotein is a rapidly evolving protein. Overall amino acid identities are only 45, 50, and 40% when the rat protein is compared with the proteins from the human, the ape, and the pig, respectively. However, the 10 cysteines are all completely invariant between these four species. The cloning of beta-microseminoprotein in the rat have substantially improved the possibilities to reveal the function of this mucosal surface protein.

Amino Acid Sequence↗
PubMed1996

Binding of vinblastine and estramustine to isolated plasma membrane fractions from human prostate and prostatic tumors.

The binding of vinblastine (VLB) and estramustine (EM) to plasma membranes isolated from human prostate, prostatic tumors as well as from Dunning rat prostatic AT-1 tumors was studied. In addition, the uptake of these drugs in AT-1 tumor cells in culture was examined. Binding of VLB was six-fold lower than that of EM in membrane preparations from all three sources. The uptake of VLB in the intact AT-1 cells was nearly five-fold lower than that of EM. At concentrations comparable to those achieved clinically the binding of EM was 100-fold higher than that of VLB. The data suggest that, owing to a very high membrane concentration of EM relative to that of VLB, the active efflux VLB in drug resistant cells would be impeded. This in turn would lead to a higher accumulation of VLB in cells that actively transport cytotoxic drugs.

Animals↗
PubMed1996

The 'Green Keyhole' nutritional campaign in Sweden: do women with more knowledge have better dietary practices?

INTRODUCTION: In 1989 the National Food Administration in Sweden introduced a food-marking symbol called the 'Green Keyhole'. The aim of the campaign is to help consumers make lowfat, high-fibre food choices. OBJECTIVE: To describe the knowledge of the Green Keyhole symbol in a general female population, and to examine whether knowledge is associated with reported intake of dietary fat and fibre. SUBJECTS: 616 randomly selected women were examined and interviewed. METHODS: Intakes of dietary fat and fibre were analysed in relation to knowledge of the Green Keyhole symbol. Knowledge was assessed by means of an open-ended question. RESULTS: 62% of the women adequately understood the meaning of the Green Keyhole. These women were significantly younger (P < 0.0001). Mean body mass index (kg/m2+/-s.e.m.) was significantly higher among the women with more knowledge of the Green Keyhole symbol than those with less knowledge: 26.4 +/- 0.2 vs 25.6 +/- 0.2, (P = 0.002). There were no major differences in total fat intake or total fibre intake between the women with less and more knowledge. However the ratios of polyunsaturated fatty acids to saturated fatty acids and fibre intake per 4200 kJ (1000 kcal) were higher (P = 0.05 and P = 0.03, respectively) and intake of saturated fatty acids was lower (P = 0.05) in the diet among women with better knowledge. CONCLUSIONS: The female population described here understands the campaign but their dietary behaviours do not appear to conform to the low-fat message.

Aged↗
PubMed1995

Preschoolers' sexual behavior at daycare centers: an epidemiological study.

The frequency of sexual behaviors in a population of preschoolers (n = 251) attending Swedish daycare centers was studied using a questionnaire given to the staff. Some behaviors turned out to be frequently occurring, like searching for body contact and responding to such contact. However, several behaviors were very uncommon (1% or fewer): touching an adult's genitals; attempting to make the adult touch the child's genitals; using objects against own or other child's genitals/anus; to masturbate obsessively, without pleasure or in a way that caused pain. Other behaviors occurred more frequently but were still uncommon (less than 2% of the children displayed such a behavior "sometimes" or "often/daily"): exhibiting own genitals; playing sexually explorative games; initiating games with a similarity to adult sexual activity; using sexual words; attempting to touch a woman's breast. Only masturbation and clinging body contact were positively correlated with behavioral disturbance. The correlations between age and single behaviors may be summarized as manifestations of the process of socialization. The results offer an incipient frame of reference for statistically normal expected sexual behaviors in preschoolers at daycare centers. The rarity of certain behaviors implies that their occurrence in an individual case may necessitate special clinical attention.

Child↗
PubMed1995

Defective B cell development and function in Btk-deficient mice.

Mutations in the Bruton's tyrosine kinase (Btk) gene have been linked to severe early B cell developmental blocks in human X-linked agammaglobulinemia (XLA), and to milder B cell activation deficiencies in murine X-linked immune deficiency (Xid). To elucidate unequivocally potential Btk functions in mice, we generated mutations in embryonic stem cells, which eliminated the ability to encode Btk pleckstrin homology or kinase domains, and assayed their effects by RAG2-deficient blastocyst complementation or introduction into the germline. Both mutations block expression of Btk protein and lead to reduced numbers of mature conventional B cells, severe B1 cell deficiency, serum IgM and IgG3 deficiency, and defective responses in vitro to various B cell activators and in vivo to immunization with thymus-independent type II antigens. These results prove that lack of Btk function results in an Xid phenotype and further suggest a differential requirement for Btk during the early stages of murine versus human B lymphocyte development.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1995

The human I alpha 1 region contains a TGF-beta 1 responsive enhancer and a putative recombination hotspot.

It appears that the switch recombination machinery of a B lymphocyte targets preferentially unrearranged heavy chain genes that have been rendered transcriptionally active. Transcriptional activation of the 'germline' human C alpha 1 and C alpha 2 genes is triggered by TGF-beta 1 and is controlled by proximal positive and distal negative regulatory elements residing upstream of the alpha 1 and alpha 2 switch regions respectively. In this report we characterize the positive proximal regulatory elements and analyse their interaction with DNA binding proteins. Our data demonstrate that a 100 bp fragment that contains a cAMP responsive element (CRE)/activating transcription factor (ATF) motif, a putative Ets binding site and an element that is created by two previously described neighbouring direct repeats (DRE), can increase the basal level of transcription and confer TGF-beta 1 inducibility to a heterologous promoter in an orientation- and position-independent manner. Ubiquitously expressed DNA binding proteins interact specifically with the CRE/ATF, the Ets site and the DRE element. Additionally, nuclear proteins interact with sequences which are located downstream of this enhancer are not essential for transcription in the transient expression assays utilized; however, they contain motifs that have been previously implicated in regulating DNA recombination events. These motifs include a Chi motif and a Chi-like element previously found in the recombination hotspot region of the Bcl-2 proto-oncogene and close to chromosomal breakpoints in T-ALL lines. Our findings raise the possibility that the intervening region associated regulatory elements in addition to regulating the transcriptional activation of the Ig heavy chain genes could also facilitate the physical interaction of transcription and recombination controlling molecular mechanisms.

Base Sequence↗