scispace - formally typeset
Search or ask a question

Showing papers by "University of Turku published in 1999"


Journal ArticleDOI
TL;DR: The role of mitogen‐activated protein kinases and AP‐1 and ETS transcription factors in the regulation of MMP gene expression during invasion process is focused on.
Abstract: Degradation of basement membranes and stromal extracellular matrix (ECM) is crucial for invasion and metastasis of malignant cells. Degradation of ECM is initiated by proteinases secreted by different cell types participating in tumor cell invasion, and increased expression or activity of every known class of proteinases (metallo-, serine-, aspartic-, and cysteine) has been linked to malignancy and invasion of tumor cells. Studies performed over the last decade have revealed that matrix metalloproteinases (MMPs) play a crucial role in tumor invasion. Expression of MMP genes is transcriptionally regulated by a variety of extracellular factors including cytokines, growth factors, and cell contact to ECM. This review will summarize the current view on the role of MMPs in tumor growth, invasion, and survival, and focus on the role of mitogen-activated protein kinases and AP-1 and ETS transcription factors in the regulation of MMP gene expression during invasion process.

1,508 citations


Journal ArticleDOI
TL;DR: The proposed definition of probiotics is based on the mechanisms of action, selection criteria, viability and non-viability, and scientifically documented health effects that will be discussed.
Abstract: Probiotics have been defined in several ways, depending on our understanding of the mechanisms of action of their effects on health and well-being of humans. The term probiotic was coined by Lilly and Stillwell [1] to describe substances produced by one microorganism, that stimulate the growth of another, thus meaning the opposite of antibiotics. Parker [2] subsequently defined probiotics as organisms and substances that contribute to intestinal balance. This definition, however, did not exclude antibiotics. At present, the most commonly used definition is that of Fuller [3] : Probiotics are live microbial feed supplements which beneficially affect the host animal by improving its intestinal microbial balance . Recently a European expert group widened the definition to include mechanisms other than just microflora mediated ones. The definition was as follows: Probiotics are live microbial food ingredients that have a beneficial effect on human health [4,5] . To include the current application and scientific data on proven effects of probiotics we propose the following definition: Probiotics are microbial cell preparations or components of microbial cells that have a beneficial effect on the health and well-being of the host . This definition implies that probiotics do not necessarily need to be viable. Non-viable forms of probiotics have also been shown to have health effects [6] . The definition does not restrict the use of probiotics in foods; several other applications have been reported to have beneficial health effects. Not only whole microbial cells, but also parts of cells have been observed to improve host health. Metabolites are, however, not included in the current definition. Thus, it excludes antibiotics. The proposed definition is based on the mechanisms of action, selection criteria, viability and non-viability, and scientifically documented health effects that will be discussed.

777 citations


Journal ArticleDOI
TL;DR: Practical implications of the participant role approach to bullying in schools are described, and it is suggested that the focus of counselling could be shifted from supporting the victims towards also working with students in other participant roles.

562 citations


Journal ArticleDOI
TL;DR: The results begin to illuminate the novel contributions of the delta subunit to GABA pharmacology and sedative/hypnotic responses and behavior and provide insights into the physiology of neurosteroids.
Abstract: γ-Aminobutyric acid (GABA) type A receptors mediate fast inhibitory synaptic transmission and have been implicated in responses to sedative/hypnotic agents (including neuroactive steroids), anxiety, and learning and memory. Using gene targeting technology, we generated a strain of mice deficient in the δ subunit of the GABA type A receptors. In vivo testing of various behavioral responses revealed a strikingly selective attenuation of responses to neuroactive steroids, but not to other modulatory drugs. Electrophysiological recordings from hippocampal slices revealed a significantly faster miniature inhibitory postsynaptic current decay time in null mice, with no change in miniature inhibitory postsynaptic current amplitude or frequency. Learning and memory assessed with fear conditioning were normal. These results begin to illuminate the novel contributions of the δ subunit to GABA pharmacology and sedative/hypnotic responses and behavior and provide insights into the physiology of neurosteroids.

523 citations


Journal ArticleDOI
TL;DR: In this article, the relationship between social intelligence, empathy, and three types of aggressive behavior were studied, and the major findings are in Line with the developmental theory by Bjorkqvist et al. [1992] suggesting that indirect aggression requires more social intelligence than direct forms of aggression.
Abstract: Relationships between social intelligence, empathy, and three types of aggressive behavior were studied. Peer-estimation techniques were used to measure all major variables. Altogether, 526 Finnish schoolchildren from three age groups (10, 12, and 14 years old) participated in the study. As was hypothesized, indirect aggression correlated positively and significantly with social intelligence in every age group studied. Physical and verbal forms of aggression had almost zero correlation to social intelligence. Empathy correlated negatively and significantly with every type of aggression except indirect aggression in 12-year-old children. The major findings are in Line with the developmental theory by Bjorkqvist et al. [1992. Aggr Behav 18:117-127] suggesting that indirect aggression requires more social intelligence than direct forms of aggression.

511 citations


Journal ArticleDOI
TL;DR: Tilt reduces respiratory gating of sympathetic and vagal motoneurone responsiveness to stimulatory inputs for different reasons; during tilt, sympathetic stimulation increases to a level that overwhelms the respiratory gate, andvagal stimulation decreases to alevel below that necessary for maximal respiratory gates to occur.
Abstract: 1. We examined interactions between haemodynamic and autonomic neural oscillations during passive upright tilt, to gain better insight into human autonomic regulatory mechanisms. 2. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in nine healthy young adults. Subjects breathed in time with a metronome at 12 breaths min-1 (0.2 Hz) for 5 min each, in supine, and 20, 40, 60, 70 and 80 deg head-up positions. We performed fast Fourier transform (and autoregressive) power spectral analyses and integrated low-frequency (0.05-0.15 Hz) and respiratory-frequency (0. 15-0.5 Hz) spectral powers. 3. Integrated areas of muscle sympathetic bursts and their low- and respiratory-frequency spectral powers increased directly and significantly with the tilt angle. The centre frequency of low-frequency sympathetic oscillations was constant before and during tilt. Sympathetic bursts occurred more commonly during expiration than inspiration at low tilt angles, but occurred equally in expiration and inspiration at high tilt angles. 4. Systolic and diastolic pressures and their low- and respiratory-frequency spectral powers increased, and R-R intervals and their respiratory-frequency spectral power decreased progressively with the tilt angle. Low-frequency R-R interval spectral power did not change. 5. The cross-spectral phase angle between systolic pressures and R-R intervals remained constant and consistently negative at the low frequency, but shifted progressively from positive to negative at the respiratory frequency during tilt. The arterial baroreflex modulus, calculated from low-frequency cross-spectra, decreased at high tilt angles. 6. Our results document changes of baroreflex responses during upright tilt, which may reflect leftward movement of subjects on their arterial pressure sympathetic and vagal response relations. The intensity, but not the centre frequency of low-frequency cardiovascular rhythms, is modulated by the level of arterial baroreceptor input. Tilt reduces respiratory gating of sympathetic and vagal motoneurone responsiveness to stimulatory inputs for different reasons; during tilt, sympathetic stimulation increases to a level that overwhelms the respiratory gate, and vagal stimulation decreases to a level below that necessary for maximal respiratory gating to occur.

492 citations


Journal ArticleDOI
TL;DR: The incidence of diarrhea after antimicrobial treatment in children with no history of antimicrobial use during the previous 3 months was evaluated and the preventive potential of Lactobacillus rhamnosus GG, a probiotic strain with a documented safety record, was assessed.
Abstract: Objectives. Antimicrobial treatment may disturb the colonization resistance of gastrointestinal microflora, which may induce clinical symptoms, most commonly diarrhea. The severity of antibiotic-associated diarrhea may range from a brief, self-limiting disease to devastating diarrhea with electrolyte disturbances, dehydration, crampy abdominal pain, pseudomembranous colitis, toxic megacolon, or even death. The incidence of diarrhea in children receiving a single antimicrobial treatment is unclear. In addition to more critical use of antimicrobials, adjunctive preventive measures to antibiotic-associated diarrhea are needed. The objective of this study was to evaluate the incidence of diarrhea after antimicrobial treatment in children with no history of antimicrobial use during the previous 3 months. Another aim of this study was to assess the preventive potential of Lactobacillus rhamnosus GG ( Lactobacillus GG ; American Type Culture Collection 53103), a probiotic strain with a documented safety record and a therapeutic effect in viral gastroenteritis on antibiotic-associated diarrhea. Methods. Oral antimicrobial agents were prescribed for the treatment of acute respiratory infections at the clinics of the Health Care Center of the City of Tampere or Tampere University Hospital, Finland, to 167 patients who were invited to participate in the study. Of the patients, 48 were lost to follow-up; therefore, the final study population consisted of 119 children from 2 weeks to 12.8 years of age (mean: 4.5 years). All study subjects met the inclusion criteria: they had not received any antimicrobial medication during the previous 3 months, they did not suffer from gastrointestinal disorders, and they did not need intravenous antimicrobial treatment. The patients were randomized to receive placebo or 2 × 10 10 colony-forming units of Lactobacillus GG in capsules given twice daily during the antimicrobial treatment. Lactobacillus GG and placebo capsules were indistinguishable in appearance and taste. The parents kept a daily symptom diary and recorded stool frequency and consistency at home for 3 months. Diarrhea was defined as at least three watery or loose stools per day for a minimum of 2 consecutive days. In the case of diarrhea, viral (adenovirus, rotavirus, calicivirus and astrovirus) and bacterial ( Salmonella, Shigella, Yersinia, Campylobacter, Clostridium difficile, Staphylococcus aureus, and yeasts) analyses were studied in fecal samples. The metabolic activity of the gut microflora was assessed by analysis of fecal urease, β-glucosidase, and β-glucuronidase activities. The primary outcome measure was diarrhea during the first 2 weeks after the beginning of the antimicrobial treatment, because this period most likely reflects the effects of antimicrobial use. Secondary outcome measures were the activities of fecal urease, β-glucuronidase, and β-glucosidase. Results. On the entire follow-up, 80% of any gastrointestinal symptoms were reported during the first 2 weeks after the beginning of the antimicrobial treatment. The incidence of diarrhea was 5% in the Lactobacillus GG group and 16% in the placebo group within 2 weeks of antimicrobial therapy (χ 2 = 3.82). The treatment effect (95% confidence interval) of Lactobacillus GG was −11% (−21%–0%). In diarrheal episodes, the viral and bacterial analyses were positive for Clostridium difficile in 2 cases and for Norwalk-like calicivirus in 3 cases. The age of the patients with diarrhea was between 3 months and 5 years in 75% of cases in both groups. The severity of diarrhea was comparable in the study groups, as evidenced by similar stool frequency (mean: 5 per day; range: 3–6) and the duration of diarrhea (mean: 4 days; range: 2–8). The activities of fecal urease and β-glucuronidase, but not β-glucosidase, changed significantly after the beginning of the antimicrobial treatment in the Lactobacillus GG group and in the placebo group alike. The decrease in urease and β-glucuronidase activities was reversible in patients with no diarrhea, but in patients with diarrhea, the modifications in gut microflora were more profound and prolonged. The activities of the three enzymes were normalized within 3 weeks, evidenced by stable enzyme activities in samples collected 3 weeks, 1 month, and 3 months after the beginning of the antimicrobial treatment, compared with those obtained before treatment. Discussion. In the present study, after a single antimicrobial treatment, the incidence of diarrhea was 16%. The higher incidence of antibiotic-associated diarrhea in previous reports may be attributable to a recent antimicrobial therapy that disturbs intestinal flora and exposes to complications. Also, in the present study, changes in the metabolic activity of the intestinal flora were observed, evidenced by a transient decline in fecal enzyme activities. Different probiotic preparations, including lactobacilli, are recommended frequently to prevent antibiotic-associated diarrhea. Although probiotics have been shown to be efficient in the prevention and the treatment of viral gastroenteritis, their usefulness during antimicrobial therapy in children has not been elucidated before. We observed that the administration of Lactobacillus GG to children receiving antimicrobial therapy for respiratory infection reduced the incidence of antibiotic-associated diarrhea to one third. The beneficial effect may be mediated by a number of functions of probiotics, ie, production of antimicrobial substances, local competition of adhesion receptors and nutrients, and stimulation of intestinal antigen specific and nonspecific immune responses. Conclusion. A probiotic strain, Lactobacillus GG , is effective in the prevention of diarrhea in children receiving antimicrobial treatment to respiratory infections.

456 citations


Journal ArticleDOI
TL;DR: Health effects related to changes in the intestinal microflora also accompany or are related to adhesion and immune system effects, competitive exclusion or metabolic and nutritional effects, with an increasing array of other potential modes of action.

439 citations


Journal ArticleDOI
TL;DR: Novel glass fiber reinforcements may considerably enhance flexural properties of multiphase dental polymers, which is due to proper impregnation of fibers with polymer matrix.
Abstract: Statement of problem. Fiber-reinforced plastics for dental applications have been under development for some time. A major difficulty in using reinforcing fibers with multiphase acrylic resins, such as powderliquid resins, has been improper impregnation of fibers with the resin. Purpose. The aim of this study was to describe and test a novel system to use polymer-preimpregnated reinforcing fibers with commonly used multiphase acrylic resins. Material and methods. Continuous unidirectional and woven preimpregnated glass fiber reinforcements (Stick and Stick Net) were used to reinforce heat-curing denture base and autopolymerizing denture base polymers. A temporary fixed partial denture polymer was also reinforced with Stick reinforcement material. Five test specimens were fabricated for unreinforced control groups and for Stick- and Stick Net-reinforced groups. A 3-point loading test was used to measure transverse strength and flexural modulus of the materials and ultimate strain at fracture was calculated. Cross-sections of test specimens were examined with a SEM to evaluate degree of impregnation of fibers with polymer matrix. Quantity of fibers in test specimens was determined by combustion analysis. Results. Transverse strength of heat-curing denture base polymer was 76 MPa, Stick reinforcement increased it to 341 MPa, and flexural modulus increased from 2550 to 19086 MPa. Stick Net reinforcement increased transverse strength of heat-curing denture base polymer to 99 MPa and flexural modulus to 3530 MPa. Transverse strength of autopolymerizing denture base polymer was 71 MPa; Stick increased it to 466 MPa; and flexural modulus increased from 2418 to 16749 MPa. Stick Net increased the transverse strength of autopolymerizing denture base polymer to 96 MPa and flexural modulus to 3573 MPa. Transverse strength of temporary fixed partial denture polymer increased from 58 to 241 MPa and flexural modulus from 1711 to 7227 MPa. ANOVA showed that reinforcement type and polymer brand affected transverse strength and modulus ( P Conclusions. Novel glass fiber reinforcements may considerably enhance flexural properties of multiphase dental polymers, which is due to proper impregnation of fibers with polymer matrix. By using Stick or Stick Net reinforcement, the strain at fracture of the material can be modified. (J Prosthet Dent 1999;81:318-26.)

425 citations


Journal ArticleDOI
TL;DR: In this paper, the authors distinguish between confined dyadic change and network change and show how change itself may be incremental or radical, using the punctuated equilibrium model of change, and introduce the concept of critical event to highlight radical change.
Abstract: This paper investigates the dynamics of business networks. We distinguish between confined dyadic change and network change and show how change itself may be incremental or radical, using the punctuated equilibrium model of change. The concept of the critical event is introduced to highlight radical change. We propose an analytical framework where the ideas of mechanism, nature and forces of change are integrated. Two circles of network change (incremental and radical) are presented and transfers from one circle to the other are discussed. We believe this conceptual elaboration may have significant implications for future network dynamic research

400 citations


Journal ArticleDOI
TL;DR: The role of MMPs and their inhibitors in tumour invasion as a basis for prognostic purposes and for targeted therapeutic intervention in cancer is discussed.
Abstract: Controlled degradation of the extracellular matrix (ECM) is crucial for the growth, invasive capacity, metastasis and angiogenesis of tumours. Matrix metalloproteinases (MMPs), a family of zinc-dependent neutral endopeptidases that are collectively capable of degrading essentially all ECM components, apparently play an important role in all of these aspects of tumour development. In addition, there is recent evidence that MMPs are also important for tumour cell survival. At present, therapeutic intervention on tumour growth and invasion based on the inhibition of MMP activity is under intensive investigation, and several MMP inhibitors are already being used on malignant tumours of various organs in clinical trials. In this review we discuss the role of MMPs and their inhibitors in tumour invasion as a basis for prognostic purposes and for targeted therapeutic intervention in cancer.

Journal ArticleDOI
TL;DR: The interim results show the efficacy and feasibility of the lifestyle intervention programme and favourable changes were also found in blood pressure, serum lipids and anthropometric indices in the intervention group.
Abstract: Aims/hypothesis. The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II (non-insulin-dependent) diabetes mellitus in subjects with impaired glucose tolerance, to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance. Methods. A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were randomised to either a control or intervention group. The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits. The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aimed at reducing weight, the intake of saturated fat and increasing the intake of dietary fibre. Intervention subjects were also guided individually to increase their physical activity. Results. During the first year, weight loss in the first 212 study subjects was 4.7 ± 5.5 vs 0.9 ± 4.1 kg in the intervention and control group, respectively (p < 0.001). The plasma glucose concentrations (fasting: 5.9 ± 0.7 vs 6.4 ± 0.8 mmol/l, p < 0.001; and 2-h 7.8 ± 1.8 vs 8.5 ± 2.3 mmol/l, p < 0.05) were significantly lower in the intervention group after the first year of intervention. Favourable changes were also found in blood pressure, serum lipids and anthropometric indices in the intervention group. Conclusion/interpretation. The interim results show the efficacy and feasibility of the lifestyle intervention programme. [Diabetologia (1999) 42: 793–801]

Journal ArticleDOI
TL;DR: The lower BMD in type 1 versus type 2 diabetic patients and control subjects probably results from more rapid bone loss after the onset of type 1 diabetes.
Abstract: OBJECTIVE: To assess the effect of type 1 and type 2 diabetes and insulin treatment on bone mineral density (BMD) in middle-aged and elderly men and women. RESEARCH DESIGN AND METHODS: We measured BMD and evaluated known determinants of osteoporosis in 56 type 1 and 68 type 2 diabetic patients and 498 nondiabetic community control subjects. All patients, aged 52-72 years, developed diabetes after the age of 30 years (i.e., after achievement of peak bone mass) and were treated with insulin. BMD was measured at the proximal femur with dual-energy X-ray absorptiometry. RESULTS: Among both sexes, BMD values were significantly lower in type 1 diabetic patients than in type 2 diabetic patients or the control subjects. When adjusted for age and BMI, the differences between type 1 diabetic patients and control subjects remained essentially unchanged in both sexes, whereas the differences between type 1 and type 2 diabetic subjects were significant only in men. After further adjustments for confounding factors, the average BMD values were still lower in type 1 diabetic subjects than in type 2 diabetic subjects although with lesser significance. Past low-energy fractures were more common in type 1 diabetic women than in type 2 diabetic women. CONCLUSIONS: The lower BMD in type 1 versus type 2 diabetic patients and control subjects probably results from more rapid bone loss after the onset of type 1 diabetes. This cannot be explained by insulin treatment, which was prescribed for both types of patients. Because the causes of low BMD in type 1 diabetes are unknown, these patients should be evaluated for the risk of osteoporosis and related fractures and offered appropriate preventive measures.

Journal ArticleDOI
TL;DR: In this paper, the effect of polymerization current density and monomer concentration on the formation of the film structure was studied with cyclic voltammetry, in situ UV-VIS-spectroelectrochemistry, electrochemical quartz crystal microbalance technique (EQCM), and in situ Fourier transform infrared (FTIR) spectroscopy using external and internal reflection techniques.

Journal ArticleDOI
TL;DR: In this paper, three dimensions of self-esteem (SE) were related to each other and to adolescents' social behavior, and adolescents' SE profiles were associated with their behavior in bullying situations; these connections were stronger among boys than among girls.
Abstract: Three dimensions of self-esteem (SE) (self-evaluated, peer-evaluated, defensive egotism) were related to each other and to adolescents’ social behavior. In addition to exploring links between single variables, five SE profiles were formed by means of a cluster analysis and connected to adolescents’ behavior in situations of bullying. Self-and peer-evaluated SEs were significantly correlated, whereas defensive egotism was not connected to either self-or peer-evaluated SE. Adolescents’ SE profiles were associated with their behavior in bullying situations; these connections were stronger among boys than among girls. Bullying others and assisting or reinforcing the bully were typical of adolescents with so-called defensive SE. Defending the victims of bullying was typical of adolescents with genuine high SE. Being victimized by peers was most typical of adolescents with low SE and, among girls, of those in the cluster thed authors named “humble pride.” The social behavior of so-called self-belittlers did not...

Journal ArticleDOI
TL;DR: The results show that collagen-dependent induction of MMP-13 in dermal fibroblasts requires p38 activity, and is inhibited by activation of ERK1,2, suggesting that p38 MAPK may serve as a target for selective inhibition of collagen degradation, e.g. in chronic dermal ulcers.

Journal ArticleDOI
TL;DR: It is found that vagal baroreflex slopes are less when arterial pressures are falling than when they are rising and that this hysteresis exists over pressure ranges both below and above baseline levels.
Abstract: We evaluated a method of baroreflex testing involving sequential intravenous bolus injections of nitroprusside followed by phenylephrine and phenylephrine followed by nitroprusside in 18 healthy men and women, and we drew inferences regarding human sympathetic and vagal baroreflex mechanisms. We recorded the electrocardiogram, photoplethysmographic finger arterial pressure, and peroneal nerve muscle sympathetic activity. We then contrasted least squares linear regression slopes derived from the depressor (nitroprusside) and pressor (phenylephrine) phases with 1) slopes derived from spontaneous fluctuations of systolic arterial pressures and R-R intervals, and 2) baroreflex gain derived from cross-spectral analyses of systolic pressures and R-R intervals. We calculated sympathetic baroreflex gain from integrated muscle sympathetic nerve activity and diastolic pressures. We found that vagal baroreflex slopes are less when arterial pressures are falling than when they are rising and that this hysteresis exists over pressure ranges both below and above baseline levels. Although pharmacological and spontaneous vagal baroreflex responses correlate closely, pharmacological baroreflex slopes tend to be lower than those derived from spontaneous fluctuations. Sympathetic baroreflex slopes are similar when arterial pressure is falling and rising; however, small pressure elevations above baseline silence sympathetic motoneurons. Vagal, but not sympathetic baroreflex gains vary inversely with subjects' ages and their baseline arterial pressures. There is no correlation between sympathetic and vagal baroreflex gains. We recommend repeated sequential nitroprusside followed by phenylephrine doses as a simple, efficientmeans to provoke and characterize human vagal and sympathetic baroreflex responses.

Journal ArticleDOI
TL;DR: Many adolescents in need of psychiatric assessment do not receive appropriate help because their problems remain unnoticed by adults, and internalizing problems among girls seem especially likely to remain unrecognized by adults.
Abstract: Background: The aim of the study is to report parent/youth self-report agreement on emotional and behavioral symptoms among 15- to 16-year-old adolescents. Methods: A completed Child Behavior Checklist and Youth Self-Report were obtained from 580 subjects. Results: Adolescents reported significantly more problem behaviors than their parents. Adolescent girls reported a significantly higher level of distress than boys in most symptom domains. The discrepancies between parent reports and youth self-reports were greater, especially for internalizing symptoms, for girls than for boys. Conclusions: Many adolescents in need of psychiatric assessment do not receive appropriate help because their problems remain unnoticed by adults. Internalizing problems among girls seem especially likely to remain unrecognized by adults.

Journal ArticleDOI
TL;DR: It is established that mutations in SLC7A7 cDNA cause Lysinuric protein intolerance, a rare, recessive disorder with a worldwide distribution, but with a high prevalence in the Finnish population.
Abstract: Lysinuric protein intolerance (LPI; OMIM 222700) is a rare, recessive disorder with a worldwide distribution, but with a high prevalence in the Finnish population; symptoms include failure to thrive, growth retardation, muscle hypotonia and hepatosplenomegaly. A defect in the plasma membrane transport of dibasic amino acids has been demonstrated at the baso-lateral membrane of epithelial cells in small intestine and in renal tubules and in plasma membrane of cultured skin fibroblasts from LPI patients. The gene causing LPI has been assigned by linkage analysis to 14q11-13. Here we report mutations in SLC7A7 cDNA (encoding y+L amino acid transporter-1, y+LAT-1), which expresses dibasic amino-acid transport activity and is located in the LPI region, in 31 Finnish LPI patients and 1 Spanish patient. The Finnish patients are homozygous for a founder missense mutation leading to a premature stop codon. The Spanish patient is a compound heterozygote with a missense mutation in one allele and a frameshift mutation in the other. The frameshift mutation generates a premature stop codon, eliminating the last one-third of the protein. The missense mutation abolishes y+LAT-1 amino-acid transport activity when co-expressed with the heavy chain of the cell-surface antigen 4F2 (4F2hc, also known as CD98) in Xenopus laevis oocytes. Our data establish that mutations in SLC7A7 cause LPI.

Journal ArticleDOI
TL;DR: The results suggest that learning is heavily driven by the text and that children inspect illustrations only minimally and that high-ability students spent relatively more time on pertinent segments of text and illustrations.

Journal ArticleDOI
TL;DR: It is shown that TRAP can generate ROS in vitro and that cells over-expressing TRAP produce higher amounts of intracellular ROS than their parent cells, and proposed that proteins containing redox-active iron could represent a novel mechanism of physiological fragmentation of organic molecules.

Journal ArticleDOI
TL;DR: It is demonstrated that, after endothelial denudation of rat carotid artery, the mRNA of the classical estrogen receptor (ERα) is constitutively expressed at a low level whereas the expression of the novel ERβ mRNA increases >40-fold, suggesting that preferential targeting to ERβ will provide vasculoprotective estrogen analogs devoid of effects to the reproductive system.
Abstract: Estrogen-based drug therapy in cardiovascular diseases has been difficult because it has not been possible to separate the wanted vasculoprotective effect from the unwanted effects of the hormone to the reproductive system. Here, we demonstrate that, after endothelial denudation of rat carotid artery, the mRNA of the classical estrogen receptor (ERalpha) is constitutively expressed at a low level whereas the expression of the novel ERbeta mRNA increases >40-fold. Under in situ hybridization and immunohistochemistry, ERbeta mRNA and protein colocalize with the smooth muscle cells in the media and neointima. Treatment of ovariectomized female rats with the isoflavone phytoestrogen genistein, which shows 20-fold higher binding affinity to ERbeta than to ERalpha, or with 17beta-estradiol, which does not differentiate between the two receptors, provides similar dose-dependent vasculoprotective effect in rat carotid injury model. In addition in concentrations <10 microM, both ligands are equally inhibitory to the replication and migration of smooth muscle cells in vitro. However, only treatment with 17beta-estradiol, but not with genistein, is accompanied with a dose-dependent uterotrophic effect. The results suggest that preferential targeting to ERbeta will provide vasculoprotective estrogen analogs devoid of effects to the reproductive system.

Journal ArticleDOI
TL;DR: The results suggest that the 5-HTT ‘S’ promoter polymorphism is associated with an increased risk for early onset alcoholism associated with antisocial personality disorder and impulsive, habitually violent behavior.
Abstract: A common 44-base pair insertion/deletion polymorphism in the promoter region of the human serotonin transporter (5-HTT) gene has been observed to be associated with affective illness and anxiety-related traits. This biallelic functional polymorphism, designated long (L) and short (S), affects 5-HTT gene expression since the S promoter is less active than the L promoter. Since there is strong evidence of a disturbance in brain serotonergic transmission among antisocial, impulsive, and violent type 2 alcoholic subjects, we decided to test the hypothesis that the frequency of the S allele, which is associated with reduced 5-HTT gene expression, is higher among habitually violent type 2 alcoholics when compared with race and gender-matched healthy controls and non-violent late-onset (type 1) alcoholics. The 5-HTT promoter genotype was determined by a PCR-based method in 114 late onset (type 1) non-violent alcoholics, 51 impulsive violent recidivistic offenders with early onset alcoholism (type 2), and 54 healthy controls. All index subjects and controls were white Caucasian males of Finnish origin. The S allele frequency was higher among type 2 alcoholics compared with type 1 alcoholics (chi2 = 4.86, P = 0.028) and healthy controls (chi2 = 8.24, P = 0.004). The odds ratio for SS genotype vs LL genotype was 3.90, 95% Cl 1.37-11.11, P = 0.011 when type 2 alcoholics were compared with healthy controls. The results suggest that the 5-HTT 'S' promoter polymorphism is associated with an increased risk for early onset alcoholism associated with antisocial personality disorder and impulsive, habitually violent behavior.

Journal ArticleDOI
TL;DR: The major finding in this study is that depressive symptoms in neuroleptic-naive first-admission schizophrenia are associated with low presynaptic dopamine function, which appears to be hemisphere-related and may have drug-treatment implications, e.g., in prediction of response to D2 receptor blocking antipsychotic drugs.

Journal ArticleDOI
TL;DR: Estrogen and androgen induction of VEGF expression and promotion of new vessel formation may be an important paracrine mechanism by which these hormones contribute to the early phase of tumor growth of hormonal cancer.

Journal ArticleDOI
01 May 1999-Herz
TL;DR: Increasing evidence shows that TUNEL-positive cardiomyocytes and internucleosomal DNA fragmentation are associated with various cardiac diseases, including acute myocardial infarction and heart failure.
Abstract: Apoptosis is an organized, energy dependent process, which leads to cell death. Its definition is based on distinct morphological features [10] and demonstration of internucleosomal DNA degradation [27], executed by selectively activated DNAses [4, 22]. The morphologic hallmarks of apoptosis include chromatic margination, nuclear condensation and fragmentation, and condensation of the cell with preservation of organelles. The process is followed by fragmentation of the cell into membrane-bound apoptotic bodies, which undergo phagocytosis by nearby cells without associated inflammation [10, 11]. Apoptosis characteristically occurs in isolated single cells. The duration of apoptosis is estimated to be from 12 to 24 hours, but in cell culture visible morphologic changes are accomplished in less than two hours [10, 16]. Non-apoptotic cell death, a prototype of which is cell death due to ischemia (oncosis), is characterized by depletion of intracellular ATP stores, swelling of the cell with disruption of organelles and rupture of the plasma membrane [15]. Groups of necrotic cells and inflammation are found in tissues [10, 15].

Journal ArticleDOI
TL;DR: Investigation of the adhesion to human intestinal mucus of a human faecal isolate, probiotic, dairy and type culture strains foundhered micro-organisms were found to be tightly bound to the immobilised mucus.

Journal ArticleDOI
TL;DR: Recombination breakpoints were detected in all genomic regions except the capsid protein coding region, suggesting that recombination is a significant and relatively frequent mechanism in the evolution of enterovirus genomes.
Abstract: Human enteroviruses consist of more than 60 serotypes, reflecting a wide range of evolutionary divergence. They have been genetically classified into four clusters on the basis of sequence homology in the coding region of the single-stranded RNA genome. To explore further the genetic relationships between human enteroviruses and to characterize the evolutionary mechanisms responsible for variation, previously sequenced genomes were subjected to detailed comparison. Bootstrap and genetic similarity analyses were used to systematically scan the alignments of complete genomic sequences. Bootstrap analysis provided evidence from an early recombination event at the junction of the 5′ noncoding and coding regions of the progenitors of the current clusters. Analysis within the genetic clusters indicated that enterovirus prototype strains include intraspecies recombinants. Recombination breakpoints were detected in all genomic regions except the capsid protein coding region. Our results suggest that recombination is a significant and relatively frequent mechanism in the evolution of enterovirus genomes.

Journal ArticleDOI
TL;DR: TGF-beta in colostrum may prevent the development of atopic disease during exclusive breast-feeding and promote specific IgA production in human subjects.
Abstract: Background: According to data from animal and in vitro studies, transforming growth factor-β (TGF-β) has a crucial effect on 2 essential parts of the mucosal immune system: IgA production and oral tolerance induction. Objective: We sought to ascertain whether TGF-β in breast milk is associated with specific IgA production and atopic disease in human subjects. Methods: Forty-seven infants with several atopic family members were followed during their first year of life. The concentrations of TGF-β1 and TGF-β2 in maternal colostrum, mature milk, and the infants' sera were determined. The enzyme-linked immunospot assay was used to assess the infants' specific IgA production in response to β-lactoglobulin, casein, gliadin, and ovalbumin. Results: At 12 months, atopic dermatitis was confirmed in 29 of 47 infants; in 11, atopic disease had begun during exclusive breast-feeding (preweaning onset), whereas in 18 the disease manifested itself after weaning (postweaning onset). The concentrations of both TGF-β1 and TGF-β2 were higher in maternal colostrum, but not in mature milk and infants' serum, in infants with postweaning-onset atopic disease compared with those with preweaning-onset disease ( P = .0008 and P = .015, respectively). The concentration of TGF-β2 was, and that of TGF-β1 tended to be, higher in the colostrum of mothers whose infants had specific IgA-secreting cells at 3 months in response to at least one of the dietary antigens tested compared with those who did not have such cells ( P = .048 and P = .076, respectively). Conclusion: TGF-β in colostrum may prevent the development of atopic disease during exclusive breast-feeding and promote specific IgA production in human subjects. (J Allergy Clin Immunol 1999;1251-7.)

Journal ArticleDOI
TL;DR: The current state of knowledge of the α / β Hydrolase fold proteins is described, and a smaller definition of the required core and some possible future avenues of exploration are suggested.