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PubMed1989

Horizontal cell gap junctions: single-channel conductance and modulation by dopamine.

Horizontal cells form an electrically coupled network for the transmission of inhibitory signals in the outer retina. In teleosts, horizontal cell coupling is modulated by the neurotransmitter dopamine. Using voltage-clamped pairs of teleost horizontal cells, we have examined the effects of dopamine on the conductance and gating properties of the cell-to-cell channels that mediate electrical synaptic transmission. Variance analysis of the junctional current noise showed that dopamine substantially reduced the open probability of gap junction channels, from 0.75 to 0.14. Direct observation of unitary junctional gating events in poorly coupled cell pairs indicated that these channels have a unitary conductance of 50-60 pS. The elementary conductance of channels in cell pairs treated with dopamine (48.7 +/- 6.6 pS) was statistically indistinguishable from channels in untreated cells (53.2 +/- 7.2 pS). Uncoupling with octanol also yielded a similar unitary conductance (61.1 +/- 11.1 pS). Our results suggest that dopamine reduces the open probability of gap junctional channels by decreasing their open duration.

Animals↗
PubMed1995

The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy.

Mitochondrial long chain fatty acid beta-oxidation provides the major source of energy in the heart. Deficiencies of human beta-oxidation enzymes produce sudden, unexplained death in childhood, acute hepatic encephalopathy, skeletal myopathy, or cardiomyopathy. Long chain 3-hydroxyacyl-CoA dehydrogenase [LCHAD; long-chain-(S)-3-hydroxyacyl-CoA:NAD+ oxidoreductase, EC 1.1.1.211] catalyzes the third step in beta-oxidation, and this activity is present on the C-terminal portion of the alpha subunit of mitochondrial trifunctional protein. We used single-stranded conformation variance analysis of the exons of the human LCHAD (alpha subunit) gene to determine the molecular basis of LCHAD deficiency in three families with children presenting with sudden unexplained death or hypoglycemia and abnormal liver enzymes (Reye-like syndrome). In all families, the mothers had acute fatty liver and associated sever complications during pregnancies with the affected infants. The analysis in two affected children revealed a G to C mutation at position 1528 (G1528C) of the alpha subunit of the trifunctional protein on both alleles. This is in the LCHAD domain and substitutes glutamine for glutamic acid at position 474 of mature alpha subunit. The third child had this G1528C mutation on one allele and a different mutation (C1132T) creating a premature termination codon (residue 342) on the second allele. Our results demonstrate that mutations in the LCHAD domain of the trifunctional protein alpha subunit in affected offspring are associated with maternal acute fatty liver of pregnancy. This is the initial delineation of the molecular basis of isolated LCHAD deficiency.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1996

Quantal release at a neuronal nicotinic synapse from rat adrenal gland.

The neuronal nicotinic synapse in tissue slices of the adrenal medulla was studied with whole-cell patch-clamp. Excitatory postsynaptic currents (EPSCs) were evoked by local field stimulation or occurred spontaneously especially when external [K+] was increased. EPSCs were carried by channels sharing biophysical and pharmacological properties of neuronal-type nicotinic receptors (nAChRs). A single-channel conductance (gamma) of 43-45 pS was found from nonstationary variance analysis of EPSCs. Spontaneous EPSCs were tetrodotoxin-insensitive and Ca(2+)-dependent and occurred in burst-like clusters. Quantal analysis of spontaneous EPSCs gave a quantal size of 20 pA and amplitude histograms were well described by binomial models with low values of quantal content, consistent with a small number of spontaneously active release sites. However, rare large amplitude EPSCs suggest that the total number of sites is higher and that extrajunctional receptors are involved. Our estimates of quantal content and size at the chromaffin cell neuronal nicotinic synapse may be useful in characterizing central neuronal-type nicotinic receptor-mediated cholinergic synaptic transmission.

Adrenal Medulla↗
PubMed1997

The capital-asset-pricing model and arbitrage pricing theory: a unification.

We present a model of a financial market in which naive diversification, based simply on portfolio size and obtained as a consequence of the law of large numbers, is distinguished from efficient diversification, based on mean-variance analysis. This distinction yields a valuation formula involving only the essential risk embodied in an asset's return, where the overall risk can be decomposed into a systematic and an unsystematic part, as in the arbitrage pricing theory; and the systematic component further decomposed into an essential and an inessential part, as in the capital-asset-pricing model. The two theories are thus unified, and their individual asset-pricing formulas shown to be equivalent to the pervasive economic principle of no arbitrage. The factors in the model are endogenously chosen by a procedure analogous to the Karhunen-Loéve expansion of continuous time stochastic processes; it has an optimality property justifying the use of a relatively small number of them to describe the underlying correlational structures. Our idealized limit model is based on a continuum of assets indexed by a hyperfinite Loeb measure space, and it is asymptotically implementable in a setting with a large but finite number of assets. Because the difficulties in the formulation of the law of large numbers with a standard continuum of random variables are well known, the model uncovers some basic phenomena not amenable to classical methods, and whose approximate counterparts are not already, or even readily, apparent in the asymptotic setting.

Journal Article↗
PubMed2006

Common determinants of single channel conductance within the large cytoplasmic loop of 5-hydroxytryptamine type 3 and alpha4beta2 nicotinic acetylcholine receptors.

Homomeric 5-hydroxytryptamine type 3A receptors (5-HT3ARs) have a single channel conductance (gamma) below the resolution of single channel recording (966 +/- 75 fS, estimated by variance analysis). By contrast, heteromeric 5-HT3A/B and nicotinic acetylcholine receptors (nAChRs) have picosiemen range gamma values. In this study, single channel recordings revealed that replacement of cytoplasmic membrane-associated (MA) helix arginine 432 (-4'), 436 (0'), and 440 (4') residues by 5-HT3B (-4'Gln, 0'Asp, and 4'Ala) residues increases gamma to 36.5 +/- 1.0 pS. The 0' residue makes the most substantial contribution to gamma of the 5-HT3AR. Replacement of 0'Arg by aspartate, glutamate (alpha7 nAChR subunit MA 0'), or glutamine (beta2 subunit MA 0') increases gamma to the resolvable range (>6 pS). By contrast, replacement of 0'Arg by phenylalanine (alpha4 subunit MA 0') reduced gamma to 416 +/- 107 fS. In reciprocal experiments with alpha4beta2 nAChRs (gamma = 31.3 +/- 0.8 pS), replacement of MA 0' residues by arginine in alpha4beta2(Q443R) and alpha4(F588R)beta2 reduced gamma slightly. By contrast, the gamma of double mutant alpha4(F588R)beta2(Q443R) was halved. The MA -4' and 4' residues also influenced gamma of 5-HT3ARs. Replacement of nAChR alpha4 or beta2 MA 4' residues by arginine made current density negligible. By contrast, replacement of both -4' residues by arginine produced functional nAChRs with substantially reduced gamma (11.4 +/- 0.5 pS). Homology models of the 5-HT3A and alpha4beta2 nAChRs against Torpedo nAChR revealed MA -4', 0', and 4' residues within five intracellular portals. This locus may be a common determinant of ion conduction throughout the Cys loop receptor family.

Amino Acid Sequence↗
PubMed1993

Intra- and inter-individual variations in energy expenditure of 14-15-year-old schoolgirls as determined by indirect calorimetry.

Eleven 14-15-year-old schoolgirls were investigated four times within 1 year to determine variations in energy expenditure between individuals (inter-individual variability) and within subjects (intra-individual variability). Indirect calorimetry was used to determine metabolic rates in the fasting and resting state (RMR), and during physical activities which were grouped into standardized and non-standardized activities. Analyses of variance supplied information about intra- and inter-individual variabilities of rates of energy expenditure. The mean resting metabolic rate in adolescent girls was 4.41 (SD 0.40) kJ/min. The overall coefficient of variation (9.1%) was approximately twice as high as the mean coefficient within subjects (4.3%). The reproducibility of the RMR of the girls was high (significant F value of variance analysis), even over a prolonged investigation of 1 year. This seemed to depend primarily on the constant body weight during the period of investigation. A workload of 30 W on a bicycle ergometer and walking at an individually chosen speed did not reveal significant differences between inter- and intra-individual variabilities of energy metabolic rates. However, in most non-standardized activities, e.g. relaxation at home, washing dishes and vacuum cleaning, inter-individual variability was significantly higher than intra-individual variability. There are true differences in energy expenditure rates between subjects which may be demonstrated by duplicated measurements. Conclusions on future experimental design were drawn, where differences between groups rather than between individuals are to be studied.

Adolescent↗
PubMed2006

Apoptotic and morphological features of the umbilical artery endothelium in mild and severe pre-eclampsia.

BACKGROUND: The pathology of the umbilical arterial endothelium in normal pregnancy and in pregnancy complicated with pre-eclampsia remains unclear. In this study the changes that occur in the umbilical artery endothelial cells were examined and endothelial cell morphology and apoptosis were compared among control, mild, and severe pre-eclamptic subjects. METHODS: Umbilical cords with a gestational age of between 35 and 40 weeks were collected from women with normal pregnancies (n=17), mild pre-eclampsia (n=10), and severe pre-eclampsia (n=12). We studied the umbilical artery endothelial cells using flow cytometry, and light and electron microscopy. Apoptosis was measured using flow cytometry and the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling technique. The Kruskall-Wallis variance analysis and Mann-Whitney U-tests as post hoc were applied. RESULTS: In mild pre-eclamptics, the endothelial cells appeared ultrastructurally separated. A dilated endoplasmic reticulum, swollen mitochondria, and vanished mitochondrial cristae were observed. In severe pre-eclamptics, the cells were disorganized, highly contracted and vacuolated, separated from each other, and protruding prominently into the lumen. The percentages of endothelial cells that underwent apoptosis in mild (p<0.017) and severe pre-eclamptics (p<0.017) were higher than those in the controls. These apoptosis values were highest in severe pre-eclamptics (p<0.0001). CONCLUSION: Apoptosis and structural disruptions in the arterial endothelium of severe pre-eclamptics were prominent in all subjects. Increased endothelial apoptosis and structural disruptions are clinically related to intensity of pre-eclampsia, and may be associated with adaptation of the endothelial cells to pre-eclampsia.

Adult↗
PubMed1997

A re-examination of the relationship between shyness, attributional style, and depression.

Alfano, Joiner, and Perry (1994) used analysis of variance and analysis of covariance in a sample of college students to demonstrate that attributional style mediates between shyness and depression, as opposed to depression mediating between shyness and attributional style. They suggested, however, the hypothetical possibility of a third model, in which negative attributional style, rather than shyness, is the independent variable, and shyness serves as a mediator between attributional style and depression. In the current study, this alternative model was tested by using LISREL to reanalyze the Alfano et al. data. Results showed that this third model, with shyness as the mediating variable, fit the model quite poorly, in contrast to the preferred model of Alfano et al., which fit quite well. However, variants of this model, in which shyness functionally precedes both attributional style and depression, fit the data better. The substantive implications of this model for counseling practice and the methodological cautions about interpreting cross-sectional data for temporal sequences are discussed.

Depression↗
PubMed1994

Computerized nuclear morphometry and survival in renal cell carcinoma: comparison with other prognostic indicators.

Morphometric nuclear parameters were compared with patient survival for a series of 174 renal cell carcinomas (RCC) collected over a 30 yr period. Stepdown regression showed long diameter, average feret diameter, form factor and the ratio of average feret diameter to equivalent diameter to be significantly associated with survival. Nuclear area, nuclear perimeter, equivalent diameter, ratio of long diameter to average feret diameter and coefficients of variation of nuclear area and nuclear perimeter were not significantly correlated with survival. All parameters were correlated with a 3 division nuclear grading classification using analysis of variance. Multivariate analysis showed nuclear form factor, tumor stage, silver staining nucleolar organizer region numbers and proliferating cell nuclear antigen expression to be independently associated with survival. The results of this study indicate that form factor is the most discriminate morphometric parameter for RCC, providing survival data additional to that derived from tumor staging and from markers of tumor proliferation.

Carcinoma, Renal Cell↗
PubMed2004

Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein-1 in chronic pancreatitis.

BACKGROUND: Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evaluate the circulating levels of IL-6, MCP-1, TGF-beta1, IGF-1 and IGFBP-3 in patients with alcoholic chronic pancreatitis (CP). METHODS: Twelve male patients with severe CP and 11 matched controls ingested 40 g alcohol. Plasma cytokine concentrations were measured for 24 h and assessed by sandwich ELISA techniques. RESULTS: IL-6 was higher in CP at fasting and 1, 4 and 24 h after alcohol intake (P < 0.04), and a significantly greater rise was found at 1 h compared to pre-stimulatory conditions and controls (P < 0.01). MCP-1 plasma levels in CP were significantly decreased at I h (P < 0.01) and 4 h (P < 0.001) compared to pre-stimulatory levels and controls, and a variance analysis showed significantly (P < 0.001) lower post-stimulatory levels at 1 h and 4 h both in CP and in controls. Alcohol consumption (40 g), however, did not influence plasma levels of TGF-1beta, IGF-I or IGFBP-3 in either of the two groups at the time frame applied. CONCLUSIONS: Acute alcohol intake induces a rise in the plasma levels of IL-6 in CP as compared to controls. The low circulating concentrations of MCP-1 1 and 4 h following alcohol consumption might possibly reflect that this mediator acts locally via autocrine mechanisms.

Adult↗
PubMedDate not supplied

Genetic basis of human scalp hair weight: a twin study.

Human scalp hair weight has been measured in 48 pairs of German twins of known zygosity. Variance analysis indicates a strong genetic component in variability in human scalp hair weight. No sex variation upon the character is found.

Adolescent↗
PubMedDate not supplied

"Effect typology" and work ability index: evaluating the success of health promotion in elder workforce.

Changes in work ability and work interest (meaning) after the participation in a health promotion program were perceived and evaluated. Drivers of the Munich Transport Authority (n = 122) of an average age of 50 years participated in 20 health days during working time over 1 year. The evaluation instruments of the health promotion program were the Work Ability Index (WAI) developed by the Finnish Institute of Occupational Health (FIOH) and the Effect Typology developed by the Institute of Occupational Health Promotion (IBG Austria). No changes were found in the WAI score. The Effect Typology evaluated the optimal effect "evolution," i.e., psychological and noetic (mental) changes, for 50% of the participants. A variance analysis of the WAI pre-post differences according to the effect classes of the Effect Typology showed significant differences, namely an increase in the WAI in the evolution group and a drop in the recovery group. The Effect Typology is suitable for the evaluation of occupational health promotion and for the further understanding and development of the WAI.

Aging↗
PubMed2004

Serum levels of prostate-specific antigen and androgens after nasal administration of a gonadotropin releasing hormone-agonist in hirsute women.

We aimed to determine whether ovarian suppression affects the production rate of prostate-specific antigen (PSA) in hirsute women. A total of 34 hirsute women who had a modified Ferriman-Gallwey (FG) score of > or = 7 and 14, non-hirsute women as the control group were recruited for this prospective controlled study. Serum samples for evaluation of basal hormones and PSA concentration were collected and were analyzed by commercial kits and chemiluminescent enzyme immunoassay. The hirsute women were given 400 microg/day nafarelin acetate for 3 months. Basal hormones, PSA levels and FG scores were then assessed. ANOVA and Tukey test were used to compare differences in means between the hirsute and the non-hirsute group at the beginning of the study. Student's t test, Tukey test and repeated measures variance analysis were used to evaluate differences in the study group and between the women with polycystic ovary syndrome (PCOS) and idiopathic hirsutism after gonadotropin releasing hormone (GnRH)-agonist administration. Statistical significance was assumed with a value of p < 0.05. PCOS and idiopathic hirsutism were diagnosed in 58.8% and 41.2% of 34 hirsute women, respectively. Age and body mass index (BMI) were similar in the hirsute and the control group (p > 0.05). FG scores in the PCOS group (20.3 +/- 1.7) were statistically similar to those of the group with idiopathic hirsutism (17.6 +/- 1.7) (p > 0.05). The non-hirsute women had significantly lower serum PSA concentrations than the hirsute group (p < 0.001). The basal mean level of PSA was 0.095 +/- 0.001 in the PCOS, 0.0061 +/- 0.009 in the idiopathic hirsute and 0.0040 +/- 0.004 ng/ml in the control group. No significant difference in the mean PSA levels was noted between the PCOS and the idiopathic hirsute subgroups before and after GnRH agonist treatment (0.0096 +/- 0.01 and 0.0051 +/- 0.032 ng/ml, respectively) (p > 0.05). FG scores, testosterone, 17alpha-hydroxyprogesterone and dehydroepiandrosterone sulfate levels were significantly decreased in the hirsute group following treatment (p < 0.001). PSA levels in hirsute women were higher than in non-hirsute women and independent of BMI, age and androgen deprivation. PSA concentration may be mediated through extragonadal sites and possibly through a long-standing hyperandrogenemic environment such as in PCOS and idiopathic hirsutism. Further investigation as to the significance of PSA in women with hirsutism and whether antiandrogens directly act to inhibit biosynthesis of PSA is warranted.

17-alpha-Hydroxyprogesterone↗
PubMed2000

Fiber intake and childhood appendicitis.

In order to investigate the possible role of fiber in the etiology of acute appendicitis, 203 consecutive appendectomized children with histologically proved appendicitis and 1922 controls were studied by the diet history method. Statistics were performed by multivariate analysis of variance, discriminant analysis and chi 2. Appendectomized children had statistically significant lower mean daily intake of fiber (17.4 g versus 20.4 g, P < 0.001) including all fiber fractions: cellulose, uronic acid, pentose, exose and lignin. No statistical difference was found for energy, protein, carbohydrate and fat intake. Discriminant analysis proved that only cellulose and exose are independently correlated to appendicitis and lower fiber intake is thought to be the cause in 70% of the cases. Recurrent abdominal pain, chronic constipation and positive family history of appendectomy were more frequent in appendectomized children (P < 0.001). This study gives evidence that low fiber intake could play an important role in the pathogenesis of appendicitis.

Abdominal Pain↗
PubMed2005

A new concept for sensitive in situ stable isotope ratio infrared spectroscopy based on sample modulation.

Diode-laser absorption spectroscopy finds increasing applications in the emerging field of stable isotope research. To meet the requirements of the water isotopes measurement challenge in environmental research, ways have to be found to cope with the present limitations of spectroscopic systems. In this article, we discuss an approach based on the Stark effect in molecular spectra to reduce the influence of time-dependent, unwanted background structures generally superimposed on the desired signal from the spectral feature under investigation. A road map to high-sensitivity isotopic ratio measurements of water isotopes is presented. On the basis of an Allan Variance analysis of measured data, the detection limits have been calculated as a function of the integration time. To achieve the required optical density of about 6 x 10(-7) for H(2)(17)O measurements, the duty cycle has to be optimized and the implementation of a sample modulation within an optical multipass cell is a promising approach to increase the stability of spectroscopic instrumentation required for ecosystem research and airborne atmospheric platforms.

Lasers↗
PubMed2004

Serum concentrations of lipids and apolipoproteins in normal and hyperemetic pregnancies.

OBJECTIVE: Hyperemesis gravidarum (HEG) is intractable nausea and vomiting. The purpose of this study was to test the hypothesis that women with HEG have lower cholesterol and triglyceride levels, to find any role in the etiology of reduced risk of spontaneous abortion in hyperemetic patients. STUDY DESIGN: The study group consisted of 39 women with normal ongoing pregnancy and 35 women with HEG. The concentrations of triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol and apolipoprotein (apo)-A and -B were analyzed. The independent-samples t test, Mann-Whitney U test, chi2 test, Kruskal-Wallis variance analysis and Spearman's correlation were used to examine differences between groups. RESULTS: Serum HDL cholesterol, LDL cholesterol and total cholesterol, apo-A and apo-B were higher in normal pregnancies compared with hyperemetic pregnancies. There were no significant differences in apo-B/apo-A, HDL cholesterol/apo-A and total cholesterol/HDL cholesterol ratios between the hyperemetic patients and controls. A negative correlation was found between total cholesterol and serum thyroxine level. CONCLUSION: We found decreased levels of total cholesterol, LDL cholesterol, apo-A and apo-B in hyperemetic patients and the same spontaneous abortion rate in the two groups in our study.

Adolescent↗
PubMed1985

Statistical methods for describing occupational exposure measurements.

An important step in studies relating worker health to industrial exposure is the estimation of mean exposure levels. The investigator frequently has to rely on industrial hygiene measurements collected for other purposes. Samples may have been taken at several companies on different dates, and on each occasion multiple individual samplers may have been employed. Often it is not recognized that readings from such a hierarchical arrangement are correlated; for example, samples taken at the same time and location are more alike than samples taken on different days. This correlation invalidates the commonly used standard errors of sample means and the usual sample standard deviation. A component of variance analysis is suggested which quantifies within-day, between-day and between-company variation. Estimators of mean exposure are presented with correct standard errors. The techniques are illustrated by a small set of data and by a recent study of exposures to styrene in 36 companies manufacturing reinforced plastics.

Environmental Exposure↗
PubMed2002

In-vitro study of bacterial adherence to different types of intraocular lenses.

The aim of this study was to determine the adherence of Staphylococcus epidermidis to intraocular lenses made of five different biomaterials: polymethylmethacrylate (PMMA), heparinized PMMA, silicone, hydrophilic acrylic, and hydrogel. The extent of bacterial binding was measured by counting. The results were compared using a one-factor variance analysis. Adherence was weakest on hydrogel and strongest on the silicone polymer. Bacterial adherence to the implant surface must therefore depend on the hydrophobicity or hydrophilicity of the biomaterial.

Acrylates↗