Showing papers by "University of Turku published in 2000"

Environmental and Heritable Factors in the Causation of Cancer — Analyses of Cohorts of Twins from Sweden, Denmark, and Finland

Abstract: Background The contribution of hereditary factors to the causation of sporadic cancer is unclear. Studies of twins make it possible to estimate the overall contribution of inherited genes to the development of malignant diseases. Methods We combined data on 44,788 pairs of twins listed in the Swedish, Danish, and Finnish twin registries in order to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer. Statistical modeling was used to estimate the relative importance of heritable and environmental factors in causing cancer at 11 of those sites. Results At least one cancer occurred in 10,803 persons among 9512 pairs of twins. An increased risk was found among the twins of affected persons for stomach, colorectal, lung, breast, and prostate cancer. Statistically significant effects of heritable factors were observed for prostate cancer (42 percent of the risk may be explained by heritable factors; 95 percent confidence interval, 29 to 50 percent), colorectal cancer (35 perce...

Regulation of cell fate decision of undifferentiated spermatogonia by GDNF.

Abstract: The molecular control of self-renewal and differentiation of stem cells has remained enigmatic. Transgenic loss-of-function and overexpression models now show that the dosage of glial cell line-derived neurotrophic factor (GDNF), produced by Sertoli cells, regulates cell fate decisions of undifferentiated spermatogonial cells that include the stem cells for spermatogenesis. Gene-targeted mice with one GDNF-null allele show depletion of stem cell reserves, whereas mice overexpressing GDNF show accumulation of undifferentiated spermatogonia. They are unable to respond properly to differentiation signals and undergo apoptosis upon retinoic acid treatment. Nonmetastatic testicular tumors are regularly formed in older GDNF-overexpressing mice. Thus, GDNF contributes to paracrine regulation of spermatogonial self-renewal and differentiation.

Morphologic and biochemical hallmarks of apoptosis.

Abstract: Apoptosis is characterised by a series of typical morphological features, such as shrinkage of the cell, fragmentation into membrane-bound apoptotic bodies and rapid phagocytosis by neighbouring cells. This paper reviews the current knowledge on the molecular mechanisms of apoptosis as they relate to the morphologic hallmarks and their implications for the detection of apoptosis in cardiac tissue. Activation of cysteine proteases called caspases plays a major role in the execution of apoptosis. These proteases selectively cleave vital cellular substrates, which results in apoptotic morphology and internucleosomal fragmentation of DNA by selectively activated DNases. In response to several pro-apoptotic signals, mitochondria release caspase activating factors, that initiate an escalating caspase cascade and commit the cell to die. Members of the Bcl-2 oncoprotein family control mitochondrial events and are able to prevent, or induce, both apoptotic and non-apoptotic types of cell death. This suggests that different types of cell death share common mechanisms in the early phases, whereas activation of caspases determines the phenotype of cell death. Detection of apoptotic cells in tissue samples currently relies on the TUNEL assay. TUNEL-positive cardiomyocytes show morphological features of apoptosis and the typical ladder pattern in DNA electrophoresis. Thus, provided that the staining protocol is carefully standardised, this quantitative methodology provides reproducible results of the occurrence of cardiomyocyte apoptosis in cardiac samples. Recently, potentially more specific assays based on analysis of DNA fragmentation or demonstration of caspase activation have been developed. Applicability of these assays to demonstrate cardiomyocyte apoptosis should be tested.

Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins

Abstract: Objective Twin concordance data for rheumatoid arthritis (RA) on their own provide only limited insight into the relative genetic and environmental contribution to the disease. We applied quantitative genetic methods to assess the heritability of RA and to examine for evidence of differences in the genetic contribution according to sex, age, and clinical disease characteristics. Methods Data were analyzed from 2 previously published nationwide studies of twins with RA conducted in Finland and the United Kingdom. Heritability was assessed by variance components analysis. Differences in the genetic contribution by sex, age, age at disease onset, and clinical characteristics were examined by stratification. The power of the twin study design to detect these differences was examined through simulation. Results The heritability of RA was 65% (95% confidence interval [95% CI] 50–77) in the Finnish data and 53% (95% CI 40–65) in the UK data. There was no significant difference in the strength of the genetic contribution according to sex, age, age at onset, or disease severity subgroup. Both study designs had power to detect a contribution of at least 40% from the common family environment, and a difference in the genetic contribution of at least 50% between subgroups. Conclusion Genetic factors have a substantial contribution to RA in the population, accounting for ∼60% of the variation in liability to disease. Although tempered by power considerations, there is no evidence in these twin data that the overall genetic contribution to RA differs by sex, age, age at disease onset, and disease severity.

Probiotics in the management of atopic eczema.

Abstract: Background Over the last two decades the incidence of allergic diseases has increased in industrialized countries, and consequently new approaches have to be explored. Objective The potential of probiotics to control allergic inflammation at an early age was assessed in a randomized double-blind placebo-controlled study. Methods A total of 27 infants, mean age 4.6 months, who manifested atopic eczema during exclusive breast-feeding and who have had no exposure to any infant or substitute formula were weaned to probiotic-supplemented, Bifidobacterium lactis Bb-12 or Lactobacillus strain GG (ATCC 53103), extensively hydrolysed whey formulas or to the same formula without probiotics. The extent and severity of atopic eczema, the growth and nutrition of infants, and concentrations of circulating cytokines/chemokines and soluble cell surface adhesion molecules in serum and methyl-histamine and eosinophilic protein X in urine were determined. Results The SCORAD score reflecting the extent and severity of atopic eczema was 16 (7–25) during breast-feeding, median (interquartile range). After 2 months, a significant improvement in skin condition occurred in patients given probiotic-supplemented formulas, as compared to the unsupplemented group; χ2 = 12.27, P = 0.002. SCORAD decreased in the Bifidobacterium lactis Bb-12 group to 0 (0–3.8), and in the Lactobacillus GG group to 1 (0.1–8.7), vs unsupplemented 13.4 (4.5–18.2), median (interquartile range), in parallel with a reduction in the concentration of soluble CD4 in serum and eosinophilic protein X in urine. Conclusion The results provide the first clinical demonstration of specific probiotic strains modifying the changes related to allergic inflammation. The data further indicate that probiotics may counteract inflammatory responses beyond the intestinal milieu. The combined effects of these probiotic strains will guide infants through the weaning period, when sensitization to newly encountered antigens is initiated. The probiotic approach may thus offer a new direction in the search for future foods for allergy treatment and prevention strategies.

Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function.

Abstract: The recent unraveling of structures of genes for the gonadotropin subunits and gonadotropin receptors has provided reproductive endocrinologists with new tools to study normal and pathological functions of the hypothalamic-pituitary-gonadal axis. Rare inactivating mutations that produce distinctive phenotypes of isolated LH or FSH deficiency have been discovered in gonadotropin subunit genes. In addition, there is a common polymorphism in the LHbeta subunit gene with possible clinical significance as a contributing factor to pathologies of LH-dependent gonadal functions. Both activating and inactivating mutations have been detected in the gonadotropin receptor genes, a larger number in the LH receptor gene, but so far only a few in the gene for the FSH receptor. These mutations corroborate and extend our knowledge of clinical consequences of gonadotropin resistance and inappropriate gonadotropin action. The information obtained from human mutations has been complemented by animal models with disrupted or inappropriately activated gonadotropin ligand or receptor genes. These clinical and experimental genetic disease models form a powerful tool for exploring the physiology and pathophysiology of gonadotropin function and provide an excellent example of the power of molecular biological approaches in the study of pathogenesis of diseases.

A pooled analysis of magnetic fields and childhood leukaemia.

Abstract: Previous studies have suggested an association between exposure to 50–60 Hz magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis based on individual records from nine studies, including the most recent ones. Studies with 24/48-hour magnetic field measurements or calculated magnetic fields were included. We specified which data analyses we planned to do and how to do them before we commenced the work. The use of individual records allowed us to use the same exposure definitions, and the large numbers of subjects enabled more precise estimation of risks at high exposure levels. For the 3203 children with leukaemia and 10 338 control children with estimated residential magnetic field exposures levels < 0.4 μT, we observed risk estimates near the no effect level, while for the 44 children with leukaemia and 62 control children with estimated residential magnetic field exposures ≥ 0.4 μT the estimated summary relative risk was 2.00 (1.27–3.13), P value = 0.002). Adjustment for potential confounding variables did not appreciably change the results. For North American subjects whose residences were in the highest wire code category, the estimated summary relative risk was 1.24 (0.82–1.87). Thus, we found no evidence in the combined data for the existence of the so-called wire-code paradox. In summary, the 99.2% of children residing in homes with exposure levels < 0.4 μT had estimates compatible with no increased risk, while the 0.8% of children with exposures ≥ 0.4 μT had a relative risk estimate of approximately 2, which is unlikely to be due to random variability. The explanation for the elevated risk is unknown, but selection bias may have accounted for some of the increase. © 2000 Cancer Research Campaign

The cell biology of osteoclast function

Abstract: Osteoclasts are multinucleated cells responsible for bone resorption. They have developed an efficient machinery for dissolving crystalline hydroxyapatite and degrading organic bone matrix rich in collagen fibers. When initiating bone resorption, osteoclasts become polarized, and three distinct membrane domains appear: a ruffled border, a sealing zone and a functional secretory domain. Simultaneously, the cytoskeleton undergoes extensive re-organisation. During this process, the actin cytoskeleton forms an attachment ring at the sealing zone, the membrane domain that anchors the resorbing cell to bone matrix. The ruffled border appears inside the sealing zone, and has several characteristics of late endosomal membrane. Extensive vesicle transport to the ruffled border delivers hydrochloric acid and proteases to an area between the ruffled border and the bone surface called the resorption lacuna. In this extracellular compartment, crystalline hydroxyapatite is dissolved by acid, and a mixture of proteases degrades the organic matrix. The degradation products of collagen and other matrix components are endocytosed, transported through the cell and exocytosed through a functional secretory domain. This transcytotic route allows osteoclasts to remove large amounts of matrix-degradation products without losing their tight attachment to underlying bone. It also facilitates further processing of the degradation products intracellularly during the passage through the cell.

Phenolics and betacyanins in red beetroot (Beta vulgaris) root: distribution and effect of cold storage on the content of total phenolics and three individual compounds.

Abstract: The distribution of total phenolics and main betacyanins in red beetroot (Beta vulgaris) root was determined. Also, the subsequent effects of cold storage on the content of total phenolics, main betacyanins (betanin and isobetanin), and the main known ferulic acid ester (β-d-fructofuranosyl-α-d-(6-O-(E)-feruloylglucopyranoside) were determined in the peel, which is the root part containing the largest amount of total phenolics. The content of total phenolics in the red beetroot water extracts was determined according to a modification of the Folin−Ciocalteu method and expressed as gallic acid equivalents (GAE). The compounds of interest were identified by HPLC−ESI−MS and NMR techniques, and the contents of compounds were determined by HLPC analyses. The total phenolic contents in various root parts were found to decrease in the order peel, crown, flesh. Significant differences in the contents of total phenolics and individual compounds were found when the effect of cold storage (5 °C, 0−196 days) on the c...

Matrix metalloproteinases in wound repair (review).

Abstract: Wound repair is initiated with the aggregation of platelets, formation of a fibrin clot, and release of growth factors from the activated coagulation pathways, injured cells, platelets, and extracellular matrix (ECM), followed by migration of inflammatory cells to the wound site. Thereafter, keratinocytes migrate over the wound, angiogenesis is initiated, and fibroblasts deposit and remodel the granulation tissue. Cell migration, angiogenesis, degradation of provisional matrix, and remodeling of newly formed granulation tissue, all require controlled degradation of the ECM. Disturbance in the balance between ECM production and degradation leads to formation of chronic ulcers with excessive ECM degradation, or to fibrosis, for example hypertrophic scars or keloids characterized by excessive accumulation of ECM components. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, which as a group can degrade essentially all ECM components. So far, 20 members of the human MMP family have been identified. Based on their structure and substrate specificity, they can be divided into subgroups of collagenases, stromelysins, stromelysin-like MMPs, gelatinases, membrane-type MMPs (MT-MMPs), and other MMPs. In this review, the role of MMPs in normal wound repair as well as in chronic ulcers is discussed. In addition, the role of signaling pathways, in particular, mitogen-activated protein kinases (MAPKs) in regulating MMP expression is discussed as possible therapeutical targets for wound healing disorders.

The reinterpretation of dreams: An evolutionary hypothesis of the function of dreaming

Abstract: Several theories claim that dreaming is a random by-product of REM sleep physiology and that it does not serve any natural function. Phenomenal dream content, however, is not as disorganized as such views imply. The form and content of dreams is not random but organized and selective: during dreaming, the brain constructs a complex model of the world in which certain types of elements, when compared to waking life, are underrepresented whereas others are over represented. Furthermore, dream content is consistently and powerfully modulated by certain types of waking experiences. On the basis of this evidence, I put forward the hypothesis that the biological function of dreaming is to simulate threatening events, and to rehearse threat perception and threat avoidance. To evaluate this hypothesis, we need to consider the original evolutionary context of dreaming and the possible traces it has left in the dream content of the present human population. In the ancestral environment human life was short and full of threats. Any behavioral advantage in dealing with highly dangerous events would have increased the probability of reproductive success. A dream-production mechanism that tends to select threatening waking events and simulate them over and over again in various combinations would have been valuable for the development and maintenance of threat-avoidance skills. Empirical evidence from normative dream content, children's dreams, recurrent dreams, nightmares, post traumatic dreams, and the dreams of hunter-gatherers indicates that our dream-production mechanisms are in fact specialized in the simulation of threatening events, and thus provides support to the threat simulation hypothesis of the function of dreaming.

Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis.

Abstract: Despite well-documented cardiotoxic effects, doxorubicin remains a major anticancer agent. To study the role of myocardial apoptosis following doxorubicin administration, male Wistar rats were exposed to 1.25, 2.5, and 5 mg/kg of i.p. doxorubicin and terminated on days 1-7 in groups of five. Doxorubicin caused a significant (P < 0.001) and dose-dependent induction of cardiomyocyte apoptosis at 24-48 h after the injection. Repeated injections of 2.5 mg/kg given every other day resulted in peaks of apoptosis at 24 h after each injection. However, no additive effect of repeated dosing was noted. In histological samples, alterations in the cytoskeletal apparatus with focal loss of contractile elements were seen after a single injection. Myocyte necrosis was absent. Thus, acute doxorubicin-induced cardiotoxicity involves cardiomyocyte apoptosis, a potentially preventable form of myocardial tissue loss.

Saliva and dental caries.

Abstract: Caries is a unique multifactorial infectious disease. Our understanding of etiological factors, the progress of the disease, and the effectiveness of prophylactic procedures have led us to believe that we understand the disease. However, we still have too few answers to many questions: "Why can we not predict who will get the disease?" "Why do we not become immunized?" "How much saliva is enough?" or "Which salivary components are protective?" and "Which salivary components predispose for caries?" It is generally accepted, however, that saliva secretion and salivary components secreted in saliva are important for dental health. The final result, "caries to be or not to be", is a complex phenomenon involving internal defense factors, such as saliva, tooth surface morphology, general health, and nutritional and hormonal status, and a number of external factors-for example, diet, the microbial flora colonizing the teeth, oral hygiene, and fluoride availability. In this article, our aim is to focus on the effects of saliva and salivary constituents on cariogenic bacteria and the subsequent development of dental caries.

Interleukin-10 generation in atopic children following oral Lactobacillus rhamnosus GG.

Abstract: Oral Lactobacillus rhamnosus GG ingestion for 5 days to 4 weeks has been shown to alleviate clinical symptoms of gastrointestinal inflammation and atopic dermatitis. To determine whether oral Lactobacillus rhamnosus GG may act by generating immunosuppressive mediator in atopic children. Lactobacillus rhamnosus GG (ATCC 53103) at a daily dose of 2 x 1010 cfu was added for 4 weeks to the diets of nine children (mean age, 21 months) with atopic dermatitis. Blood and faecal samples were collected before supplementation and at early (2 weeks) and late stage (4 and 8 weeks from the beginning). The concentrations of interleukin-6 (IL-6), IL-10, IL-12, tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) in sera, as well as the production of IL-2, IL-4, IL-10 and IFNgamma in mitogen-induced peripheral blood mononuclear cells, were assessed. Secretory IgA and TNFalpha were also determined in faeces. The serum IL-10 concentration differed significantly between before, early and late samples (P < 0.001) due to the elevation of serum IL-10 in the later phase of oral Lactobacillus rhamnosus GG ingestion. The enhancement of IL-10 production in mitogen-induced cultures preceded the rise in serum IL-10. The enhanced IL-10 generation in vivo substantiates the anti-inflammatory properties of specific probiotic bacteria strains, and provides an additional reason for considering such treatments for patients with intestinal inflammation.

The effect of a null mutation in the follicle-stimulating hormone receptor gene on mouse reproduction.

Abstract: To investigate further brain-pituitary-gonadal interrelationships we have generated mice in which the gene encoding the FSH receptor has been disrupted. Female FSH receptor knockout (FSHRKO) mice were infertile. The ovaries were significantly reduced in size, with follicular development arrested at the preantral stage, but there was evidence of stromal hypertrophy. The vagina was imperforate, and the uterus was atrophic. There was no response to administration of PMSG. Inhibins A and B were undetectable in both the serum and gonads. Compared with those in control animals, serum concentrations of FSH and LH were significantly elevated in mutant females. The pituitary content of FSH, but not LH, was also significantly elevated. Estrogen administration in FSHRKO female mice suppressed serum LH levels to those seen in control mice, whereas FSH levels were reduced by only 50%. Male FSHRKO mice were fertile, although testis weight was significantly reduced. However, testicular inhibin A and B concentrations did not differ from those in normal littermates. Serum levels of FSH and LH were elevated in the null mutant male mice, whereas no differences were found in the pituitary content of these hormones. In conclusion, ovarian follicular development cannot progress beyond the preantral stage without FSH. In the absence of mature follicles ovarian estrogen remains low, and consequently accessory sex tissue growth and negative feedback regulation of gonadotropin secretion are severely compromised. In the male, however, inability to respond to FSH does not impair fertility, although testicular weight is reduced, and feedback regulation of pituitary gonadotropins and intratesticular paracrine interactions may be disturbed.

Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption.

Abstract: Human serum contains two forms of tartrate-resistant acid phosphatase (TRAP), 5a and 5b. Of these, 5a contains sialic acid and 5b does not. We show here that antigenic properties and pH optimum of TRAP purified from human osteoclasts are identical to those of serum TRAP 5b and completely different from those of serum TRAP 5a, suggesting that 5b would be derived from osteoclasts and 5a from some other source. We developed a novel immunoassay specific for 5b using a monoclonal antibody O1A as capture antibody. O1A did not bind acid phosphatase derived from platelets and erythrocytes. Western analysis showed that O1A was specific for TRAP in both human bone and serum. We measured bound TRAP activity at pH 6.1, where 5b is highly active and 5a almost completely inactive. The immunoassay detected more than 90% of the initial TRAP 5b activity after 8-h incubation of serum samples at 25 degrees C and after 3 days incubation at 4 degrees C. Serum TRAP 5b activity decreased significantly after 6 months of hormone replacement therapy (HRT) of postmenopausal women compared with the change observed in postmenopausal women receiving placebo (p < 0.0001). Instead, no significant differences were observed between the changes in the placebo and HRT groups in total serum TRAP amount. These results show that serum TRAP 5b is a specific and sensitive marker for monitoring antiresorptive treatment. Instead, total serum TRAP cannot be used for that purpose. These findings may turn out to be a significant improvement in using serum TRAP as a resorption marker.

Estradiol acts as a germ cell survival factor in the human testis in vitro.

Abstract: The necessity of estrogens for male fertility was recently discovered in studies on both estrogen receptor alpha knockout and aromatase (cyp 19 gene) knockout mice. However, direct testicular effects of estrogens in male reproduction have remained unclear. Here we studied the protein expression of ERalpha and the recently described estrogen receptor beta in the human seminiferous epithelium and evaluated the role of 17beta-estradiol, the main physiological estrogen, in male germ cell survival. Interestingly, both estrogen receptors alpha and beta were found in early meiotic spermatocytes and elongating spermatids of the human testis. Furthermore, low concentrations of 17beta-estradiol (10(-9) and 10(-10) mol/L) effectively inhibited male germ cell apoptosis, which was induced in vitro by incubating segments of human seminiferous tubules without survival factors (i.e. serum and hormones). Dihydrotestosterone, which, in addition to estradiol, is an end metabolite of testosterone, was also capable of inhibiting testicular apoptosis, but at a far higher concentration (10(-7) mol/L) than estradiol. Thus, estradiol appears to be a potent germ cell survival factor in the human testis. The novel findings of the present study together with the previously reported indirect effects of estrogens on male germ cells indicate the importance of estrogens for the normal function of the testis.

Farm environment in childhood prevents the development of allergies

Abstract: Background A protective effect of infections in early life might explain the firmly reported finding of an inverse association between atopic disorders and large sibships. Objective To study the effect of childhood farm, rural non-farm and urban environment, as well as family size and other factors on the occurrence of asthma, wheezing and atopic disorders up to young adulthood. Methods Data on lifetime prevalence of physician-diagnosed asthma, allergic rhinitis and/ or allergic conjunctivitis, atopic dermatitis, as well as self-reported episodic wheezing from 10667 Finnish first-year university students aged 18-24 years were collected by a postal questionnaire. Associations of lifetime prevalence of the diseases with living on a farm, in a rural non-farm and urban environment during childhood were estimated by logistic regression analysis. Adjustment was made for potential confounding by gender, parental atopy, parental education, number of older siblings, day care outside the home and passive smoking. Results The childhood farm environment independently reduced the risk for physician-diagnosed allergic rhinitis and/or allergic conjunctivitis (adjusted odds ratio 0.63, 95% CI 0.50-0.79, P < 0.001), and for diagnosed asthma and episodic wheezing analysed together (OR 0.71, 95% CI 0.54-0.93, P < 0.05), but not for atopic dermatitis during lifetime. Urban childhood environment did not show independent increased risk when compared with rural non-farm residence. The inverse association of sibship size with the occurrence of allergic rhinitis and/or allergic conjunctivitis was found among subjects with one (OR 0.86, 95% Cl 0.77-0.96, P < 0.01) or at least four older siblings (OR 0.47, 95% Cl 0.26-0.84, P < 0.05). Conclusion Childhood farm environment seems to have a protective effect against allergic rhinitis and/or conjunctivitis, and more weakly against asthma and wheezing irrespective of family size. Environmental exposure to immune modulating agents, such as environmental mycobacteria and actinomycetes, favouring manifestation of a nonatopic phenotype could explain the finding.

The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia

Abstract: While genetic influences in schizophrenia are substantial, the disorder's molecular genetic basis remains elusive. Progress has been hindered by lack of means to detect nonpenetrant carriers of the predisposing genes and by uncertainties concerning the extent of locus heterogeneity. One approach to solving this complexity is to examine the inheritance of pathophysiological processes mediating between genotype and disease phenotype. Here we evaluate whether deficits in neurocognitive functioning covary with degree of genetic relationship with a proband in the unaffected MZ and DZ co-twins of patients with schizophrenia. Twin pairs discordant for schizophrenia were recruited from a total population cohort and were compared with a demographically balanced sample of control twin pairs, on a comprehensive neuropsychological test battery. The following four neuropsychological functions contributed uniquely to the discrimination of degree of genetic loading for schizophrenia and, when combined, were more highly correlated within MZ pairs than within DZ pairs, in both discordant and control twins: spatial working memory (i.e., remembering a sequence of spatial locations over a brief delay), divided attention (i.e., simultaneous performance of a counting and visual-search task), intrusions during recall of a word list (i.e., "remembering" nonlist items), and choice reaction time to visual targets. Together with evidence from human and animal studies of mediation of these functions by partially distinct brain systems, our findings suggest that there are multiple independently inherited dimensions of neural deficit in schizophrenia and encourage a search for genes contributing to quantitative variation in discrete aspects of disease liability. On tests of verbal and visual episodic memory, but not on the liability-related measures, patients were more impaired than their own MZ co-twins, suggesting a preferential impact of nongenetic influences on long-term memory systems.

Power and empowerment in nursing: three theoretical approaches.

Abstract: Power and empowerment in nursing: three theoretical approaches Definitions and uses of the concept of empowerment are wide-ranging: the term has been used to describe the essence of human existence and development, but also aspects of organizational effectiveness and quality. The empowerment ideology is rooted in social action where empowerment was associated with community interests and with attempts to increase the power and influence of oppressed groups (such as workers, women and ethnic minorities). Later, there was also growing recognition of the importance of the individual’s characteristics and actions. Based on a review of the literature, this paper explores the uses of the empowerment concept as a framework for nurses’ professional growth and development. Given the complexity of the concept, it is vital to understand the underlying philosophy before moving on to define its substance. The articles reviewed were classified into three groups on the basis of their theoretical orientation: critical social theory, organization theory and social psychological theory. Empowerment seems likely to provide for an umbrella concept of professional development in nursing.

Matrix metalloproteinases in tumor invasion.

Abstract: Controlled degradation of extracellular matrix (ECM) is essential for the growth, invasion, and metastasis of malignant tumors, and for tumor-induced angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all ECM components and they apparently play an important role in all these aspects of tumor development. Furthermore, recent evidence suggests that MMPs also play a role in tumor cell survival. In this review, we discuss the current concept concerning the role of MMPs and their inhibitors in tumor invasion, as a basis for prognosis and targeted therapeutic intervention in cancer.

Alpha-synuclein-immunoreactive cortical Lewy bodies are associated with cognitive impairment in Parkinson's disease

Abstract: Amygdala, hippocampus and six cortical gyri were examined for the Lewy body (LB) degeneration and Alzheimer’s disease (AD) type changes in 45 patients with Parkinson’s disease (PD). For detection of LBs, the brain areas were stained with an antibody against alpha-synuclein. The extent of neuropathological lesions was investigated in relation to cognitive dysfunction and apolipoprotein E (apoE) ɛ4 allele dosage. At least one cortical LB was found in 95% of cases (43/45). Furthermore, 40% of cases (18/45) had histological findings of definite AD (CERAD class C). Those PD cases with the apoE ɛ4 allele had a significantly greater number of cortical LBs than those without the apoE ɛ4 allele, but this was statistically significant only in precentral, angular and temporal gyri. The LB density correlated better with the number of plaques than with the density of tangles. The number of LBs in several cortical areas correlated significantly with the cognitive impairment. In stepwise linear regression analysis, the number of LBs in the cingulate gyrus and the amount of tangles in the temporal cortex remained statistically significant. When the CERAD class C was excluded, the correlation between cognitive decline and the number of LBs in cortical areas became even more pronounced. A stepwise linear regression analysis in these cases found the number of LBs in the frontal gyrus to be the statistically most significant predictor of cognitive impairment. This study shows, for the first time, that in PD, alpha-synuclein-positive cortical LBs are associated with cognitive impairment independent of AD-type pathology.

Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer.

Abstract: DNA amplification at chromosomal region 20q12-q13, which is common in breast cancer, has recently been described also in ovarian tumors. We studied the amplification of the recently identified candidate oncogenes in this region in 24 sporadic, 3 familial and 4 hereditary ovarian carcinomas, and in 8 ovarian cancer cell lines. High-level amplification of at least one of the five nonsyntenic regions at 20q12-q13.2 was found in 13 sporadic (54%) and in all four hereditary tumors. Typically, two or more distinct amplicons (separated by nonamplified DNA) were found coamplified in various combinations. The regions defined by the AIB1 and PTPN1 genes (at 20q12 and 20q13.1, respectively) were amplified in 25% and 29% of the sporadic tumors, also without simultaneous coamplification of other regions. Amplification of AIB1 (a steroid receptor coactivator gene) was associated with estrogen receptor positivity in sporadic ovarian carcinomas (P = 0.01) and showed a tendency to correlate with poor survival of patients. Of the genes amplified in breast cancer, the BTAK gene was amplified in 21%, the MYBL2 gene in 17%, and the ZNF217 gene in 12.5% of the sporadic tumors. The high frequency of gene amplification at 20q12-q13.2 suggests that the genes amplified therein may play a central role in the pathogenesis of sporadic and hereditary ovarian carcinoma.

Cognitive impairment and the brain dopaminergic system in Parkinson disease: [18F]fluorodopa positron emission tomographic study.

Abstract: Objective To investigate the role of the brain dopaminergic system in cognitive impairment in patients with Parkinson disease (PD). Design We studied 28 patients with PD and 16 age-matched healthy control subjects using [ 18 F]fluorodopa (fluorodopa F 18) positron emission tomography. Patients with PD showed a variable degree of cognitive impairment, which was assessed using the Mini-Mental State Examination and detailed neuropsychologic assessment, including tests sensitive for frontal lobe function. Results [ 18 F]Fluorodopa uptake was reduced in the putamen (to 36% of the control mean; P P P 18 F]fluorodopa uptake values. The influx constant ( K i occ ) in the caudate nucleus had a negative association with performance in the attention-demanding Stroop interference task, especially with the interference time. The K i occ in the frontal cortex had a positive correlation with performance in the digit span (backwards), verbal fluency, and verbal immediate recall tests. Thus, the better the patient performed in tasks demanding immediate and working memory and executive strategies, the better the [ 18 F]fluorodopa uptake in the frontal cortex. In the putamen, no significant correlation was seen between the K i occ value and any of the cognitive tests. The severity of the motor symptoms of PD and [ 18 F]fluorodopa uptake showed a negative correlation in the putamen ( r = −0.38; P = .04), and in the caudate nucleus a similar trend was seen ( r = −0.36; P = .06). Conclusions Reduced [ 18 F]fluorodopa uptake in PD in the caudate nucleus (and frontal cortex) is related to impairment in neuropsychologic tests measuring verbal fluency, working memory, and attentional functioning reflecting frontal lobe function. This indicates that dysfunction of the dopamine system has an impact on the cognitive impairment of patients with PD. However, our results do not exclude the possibility of more generalized cognitive impairment in PD, the pathophysiology of which is probably different and more generalized.

Numerical responses of different trophic groups of invertebrates to manipulations of plant diversity in grasslands.

Abstract: We studied the effects of plant diversity on abundance of invertebrate herbivores, parasitoids and predators in two grassland communities (one in Switzerland and one in Sweden) in which plant species richness and functional diversity have been experimentally manipulated. Among herbivores, the abundance of only the most sessile and specialised groups (leafhoppers and wingless aphids) was affected by plant diversity. At both sites, numbers of leafhoppers in sweep net samples showed a linear, negative relationship with plant species number whereas numbers of wingless aphids in suction samples increased with the number of plant functional groups (grasses, legumes, and non-legume forbs) present in the plot. Activity of carabid beetles and spiders (as revealed by pitfall catches) and the total number of predators in pitfalls at the Swiss site decreased linearly with increases in the number of plant species and plant functional groups. Abundance of more specialised enemies, hymenopteran parasitoids, was not affected by the manipulations of plant diversity. Path analysis and analysis of covariance indicated that plant diversity effects on invertebrate abundance were mostly indirect and mediated by changes in plant biomass and cover. At both sites, plant species composition (i.e. the identity of plant species in a mixture) affected numbers of most of the examined groups of invertebrates and was, therefore, a more important determinant of invertebrate abundance in grasslands than plant species richness per se or the number of plant functional groups. The presence of legumes in a mixture was especially important and led to higher numbers of most invertebrate groups. The similarity of invertebrate responses to plant diversity at the two study sites indicates that general patterns in abundance of different trophic groups can be detected across plant diversity gradients under different environmental conditions.

The quality of life in Parkinson's disease.

Abstract: The objective of this study was to examine the quality of life in patients with Parkinson's disease (PD) in a community-based sample (n = 228 patients) using a Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) as a measure. Associations to the variables age, age at onset, duration, clinical stage (Hoehn and Yahr), depression (Zung), and dementia (MMSE) were studied. Women scored significantly lower on five of the eight dimensions of SF-36. Depression, as measured in this study, was more common among parkinsonian women than men. Depression was the factor that was associated most significantly with the experienced quality of life, according to SF-36. With physical functioning, only the clinical stage had a more significant association than depression. To improve the quality of life in patients with PD, it is necessary to make every effort to recognize and relieve the depression of patients with PD.