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PubMed2005

Determinants of temporal variability in NHEXAS-Maryland environmental concentrations, exposures, and biomarkers.

The longitudinal NHEXAS-Maryland study measured metals, PAHs, and pesticides in several media to capture temporal variability. Questionnaires were concurrently administered to identify factors that influenced changes in contaminant levels over time. We constructed mixed-effects regression models for lead, phenanthrene, and chlorpyrifos (including metabolites) in indoor air, dust, dermal wipes, and biological fluids. Significant predictors represented time-varying activities as well as unchanging housing and demographic factors. There was little overlap among the models, with predictors generally reflecting the diverse characteristics of the target compounds. We estimated between- and within-person variance components to evaluate the reliability of the measurements. While only one measurement of lead in blood or chlopyrifos in dust was needed for a dependable estimate of an individual's average level, three to eight measurements were needed for most other compound/exposure medium combinations because of considerable temporal variability. Measurements in biological fluids and dust were generally more consistent than those in indoor air. The significant covariates in the full models preferentially reduced the between-person variance component. Since the regression models explained only 1-37% of the within-person variance, the questionnaires in this study provided only modest insight into the factors responsible for the temporal variability in the contaminant levels.

Air Pollution, Indoor↗

PubMed2002

Cerebrospinal fluid corticotropin-releasing factor (CRF) and vasopressin concentrations predict pituitary response in the CRF stimulation test: a multiple regression analysis.

There is considerable evidence that stress-related psychiatric disorders, including depression and post-traumatic stress disorder (PTSD), are associated with hypersecretion of corticotropin-releasing factor (CRF) within the central nervous system (CNS). One line of evidence that is consistent with central CRF hypersecretion in these disorders is the blunted adrenocorticotropin hormone (ACTH) response to intravenous CRF administration, likely a consequence, at least in part, of downregulation of anterior pituitary CRF receptors. The present study tests the hypothesis that elevated cerebrospinal fluid (CSF) concentrations of CRF and a secondary ACTH secretagogue, arginine vasopressin (AVP), are associated with diminished adenohypophyseal responses in a standard CRF stimulation test. CSF concentrations of CRF and AVP, and plasma ACTH responses to the administration of 1 microg/kg ovine CRF (oCRF) were measured in healthy adult women with and without current major depression and/or a history of significant childhood abuse. The primary outcome measure was ACTH area under the curve (AUC) in the CRF stimulation test. Multiple linear regression was performed to identify the impact of CSF CRF and AVP concentrations upon the pituitary response to CRF stimulation. The regression model explained 56.5% of the variation in the ACTH response to CRF stimulation. The relationship of CSF concentrations of CRF to ACTH responses to CRF were best described by a third-order function that was inversely correlated over most of the range of studied values. The association of ACTH response with CSF concentration of AVP and the dose of oCRF followed second-order kinetics. These findings support the hypothesis that central CRF hypersecretion is associated with a blunted ACTH response to exogenously administered CRF, explaining almost 60% of the variation in the ACTH response to CRF.

Adrenocorticotropic Hormone↗

PubMed2001

Histone H3 phosphorylation and cell division.

Histone H3 is specifically phosphorylated during both mitosis and meiosis in patterns that are specifically coordinated in both space and time. Histone H3 phosphorylation may initiate at different phases of the cell division in different organisms, but metaphase chromosomes are always found to be heavily phosphorylated. Upon exit of mitosis/meiosis a global dephosphorylation of H3 takes place. Potential candidates for H3 kinases are described and their hypothetical mechanism of action on highly condensed chromatin templates is discussed. In addition, a novel hypothesis for the role of histone H3 phosphorylation during cell division is proposed. This hypothesis, termed the 'ready production label' model, explains the results in the literature and suggests that phosphorylation of histone H3 is a part of a complex signaling mechanism.

Animals↗

PubMed1997

Intrinsic molecular fluorescence of lactate dehydrogenase: an analytical alternative for enzymic determination of pyruvate.

A method for the enzymic determination of pyruvate based on changes in the fluorescence intensity of lactate dehydrogenase (LDH) is described. These changes are due to the differential quenching effect produced by NAD and NADH on the LDH fluorescence. The NADH quenching is due to both an inner filter effect and LDH-NADH complex formation; the LDH-NADH complex is also fluorescent. However, the NAD quenching is based only on the inner filter effect. From these suppositions, the equilibrium constant of the reaction and the formation constant of the LDH-NADH complex were obtained. Given this, an appropriate analytical signal for the quantification of pyruvate and a mathematical model explaining the effect of each parameter are proposed. The linear response range of the method depends on the NADH concentration used during the determination; it is possible to determine pyruvate concentrations down to 8.8 x 10(-7) mol dm-3. The method was applied to the determination of pyruvate in synthetic blood samples with good accuracy.

Animals↗

PubMed2005

Ring currents in the porphyrins: pi shielding, delocalisation pathways and the central cation.

It is shown that the ipsocentric orbital-based model explains how the charge of the central cation drives the delocalisation pathway in metalloporphyrins. A positive charge +Ze at the centre of the porphin ring gives rise to a two-way radial transfer of charge within the pi structure of the porphin macrocycle. This manifests itself in a change of pathway of the global pi current, as Z increases from Z = 0, from an inner- through a bifurcated- to an outer-pathway. Changes of pathway can be interpreted in terms of a specific pi shielding effect whereby electrons in high-lying pi orbitals are screened from the central charge by the electrons in lower-lying orbitals of the same symmetry. These changes in pi structure are essentially independent of accompanying changes in the sigma structure.

Cations↗

PubMed1993

Annexin 5 as a potential regulator of annexin 1 phosphorylation by protein kinase C. In vitro inhibition compared with quantitative data on annexin distribution in human endothelial cells.

In vitro phosphorylation of annexin 1 by purified rat brain protein kinase C (PKC) has been studied in the presence of annexin 5, which is not a substrate for PKC. Annexin 5 promoted a dose-dependent inhibition of annexin 1 phosphorylation, which could be overcome by increasing the concentration of phosphatidylserine (PtdSer). In addition, a close relationship was found between the amount of PtdSer uncovered by annexin 5 and the residual phosphorylation of annexin 1. These data fit with the 'surface depletion model' explaining the antiphospholipase activity of annexins. In order to check the possibility that the in vitro effect of annexin 5 could be of some physiological relevance, annexins 1, 2, and 5, as well as the light chain of calpactin 1 (p11), have been quantified in human endothelial cells by measuring the radioactivity bound to the proteins after Western blotting with specific antibodies and 125I-labelled secondary antibody. Our data indicate that annexins 1 and 5, PKC and PtdSer are present in human endothelial cells in relative amounts very similar to those used in vitro under conditions permitting the detection of the inhibitory effect of annexin 5. Since annexin 1 remained refractory to PKC-dependent phosphorylation in intact cells, we suggest that annexin 5 might exert its inhibitory effect towards PKC in vivo, provided that its binding to phospholipids can occur at physiological (micromolar) concentrations of Ca2+. This was previously shown to occur in vitro using phosphatidylethanolamine/phosphatidic acid vesicles [Blackwood and Ernst (1990) Biochem. J. 266, 195-200]. Using identical assay conditions, which also allowed expression of PKC activity, annexin 5 again inhibited annexin 1 phosphorylation without interfering with PKC autophosphorylation. These data suggest that annexins 1 and 5 might interact with each other on the lipid surface, resulting in a specific inhibition of annexin 1 phosphorylation by PKC. Whether a similar mechanism also occurs in vivo remains to be determined.

Adenosine Triphosphate↗

PubMed2002

Predictors of parental adjustment to children's epilepsy in rural India.

BACKGROUND: Negative societal attitudes towards disability affect the adjustment of parents when their child is diagnosed with epilepsy. Recent studies have suggested that parental and child outcomes, including adjustment, can be influenced by non-directed social support to mothers of children with disability. The objective of our study was to test the hypothesis that maternal satisfaction with social support, measured at the beginning of treatment, would predict parental adjustment to the child's epilepsy after 1 year of treatment. METHODS: We enrolled 46 mothers of children aged 6-18 years with epilepsy in the study. We measured social support using the modified Dunst family support scale, and parental adjustment using a locally validated instrument (S-PAM). Correlation was tested using a multiple linear regression model, allowing for confounding variables. RESULTS: Parental adjustment at outcome was positively independently correlated with satisfaction with social support at baseline,and negatively with severity of the child's epilepsy. The regression model explained 34% of the total variance. CONCLUSIONS: Taken together with evidence from previous studies, this finding supports the idea that helping parents to find more satisfaction within their (new or existing) social networks will promote adjustment to their child's disability.

Adaptation, Psychological↗

PubMed2001

Glomerular protein sieving and implications for renal failure in Fanconi syndrome.

BACKGROUND: Glomerular sieving coefficients (GSCs) of proteins have been measured extensively in animals but not humans. We have studied the proteinuria of Fanconi syndrome, a "knock-out" of renal tubular protein reabsorption, to estimate GSCs and detect potential contributors to development of renal failure. METHODS: Immunoassay of proteins and polypeptides in serum and urine of patients with early Dent's disease (mean GFR = 83 mL/min, range 60 to 101, N = 5), Lowe's syndrome (N = 3), and ADIF (N = 2) were used. RESULTS: Twenty-one proteins, ranging in mass from insulin (5.1 kD) and parathyroid hormone (PTH; 9.4 kD) to transferrin (78 kD) and intact IgG (160 kD), were present in Fanconi urine at> 6 to 1000-fold normal. A simple model assuming complete "knock-out" of the reuptake of each protein filtered normally by the glomerulus was applied to protein excretion by Dent's patients. GSCs were estimated for 12 plasma proteins, including albumin (7.7 +/- 0.9 x 10-5) and IgG (4.2 +/- 0.28 x 10-5; mean +/- SEM). We calculated the albumin concentration in normal glomerular filtrate to be 3.5 +/- 0.41 mg/L (53 +/- 6.4 nmol/L), consistent with studies in rat and dog. CONCLUSIONS: To our knowledge, this study provides the first estimates of human in vivo GSCs. Our model explains why tubular proteinuria of Fanconi syndrome includes proteins of mass of albumin and above as well as low-molecular-weight proteins, and further characterizes the endocytic pathway(s) believed defective in these syndromes. High urinary concentrations of potentially bioactive hormones such as PTH, insulin, IGF-1 and the chemokine monocyte chemoattractant protein-1 (MCP-1), were found; their presence in tubular fluid may contribute to the hypercalciuria, interstitial fibrosis, and the progressive renal failure of Fanconi syndromes.

Animals↗

PubMedDate not supplied

The minerals of milk.

The salt of milk constitutes a small part of milk (8-9 g.L(-1)); this fraction contains calcium, magnesium, sodium and potassium for the main cations and inorganic phosphate, citrate and chloride for the main anions. In milk, these ions are more or less associated between themselves and with proteins. Depending on the type of ion, they are diffusible (cases of sodium, potassium and chloride) or partially associated with casein molecules (cases of calcium, magnesium, phosphate and citrate), to form large colloidal particles called casein micelles. Today, our knowledge and understanding concerning this fraction is relatively complete. In this review, the different models explaining (i) the nature and distribution of these minerals (especially calcium phosphate) in both fractions of milk and (ii) their behaviour in different physico-chemical conditions, are discussed.

Animals↗

PubMedDate not supplied

[Bacterial enterotoxin receptors].

Bacterial enterotoxin receptors. Enteric bacterial toxins display a great diversity in their structure, molecular weight and mechanism of action. The interaction of enterotoxins with the intestinal mucosa either leads to a direct effect on the cell membrane or an effect on signal transduction within eukaryotic cells. However, before a toxin can affect a cell, it must after its secretion by a microorganism, recognise and bind to a specific surface molecule, its receptor. Membrane receptors of bacterial enterotoxins have been identified as protein, glycoprotein or glycolipid in nature. The chemical nature of the molecules acting as receptors is crucial and during evolution they have been carefully selected. Some toxins, after their interaction with a receptor molecule, will transduce a signal across the cell membrane while remaining at the cell surface. Other toxins, after this initial binding step with a receptor, will be internalised. Others can form pores leading to leakage of cellular components and cell lysis. Receptors that have been identified often comprise a saccharidic chain that is directly involved in the recognition and binding of the toxin. Today, models explaining toxin-receptor interactions are more complex, including multistep events. This review summarises the knowledge of the interactions between bacterial toxins and membrane receptors present on intestinal mucosa.

Animals↗

PubMed2002

Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?

BACKGROUND & AIMS: Comorbid or extraintestinal symptoms occur frequently with irritable bowel syndrome and account for up to three fourths of excess health care visits. This challenges the assumption that irritable bowel is a distinct disorder. The aims of this study were to (1) assess comorbidity in 3 areas: gastrointestinal disorders, psychiatric disorders, and nongastrointestinal somatic disorders; and (2) evaluate explanatory hypotheses. METHODS: The scientific literature since 1966 in all languages cited in Medline was systematically reviewed. RESULTS: Comorbidity with other functional gastrointestinal disorders is high and may be caused by shared pathophysiological mechanisms such as visceral hypersensitivity. Psychiatric disorders, especially major depression, anxiety, and somatoform disorders, occur in up to 94%. The nongastrointestinal nonpsychiatric disorders with the best-documented association are fibromyalgia (median of 49% have IBS), chronic fatigue syndrome (51%), temporomandibular joint disorder (64%), and chronic pelvic pain (50%). CONCLUSIONS: Multivariate statistical analyses suggest that these are distinct disorders and not manifestations of a common somatization disorder, but their strong comorbidity suggests a common feature important to their expression, which is most likely psychological. Some models explain the comorbidity of irritable bowel with other disorders by suggesting that each disorder is the manifestation of varying combinations of interacting physiological and psychological factors. An alternative hypothesis is that the irritable bowel diagnosis is applied to a heterogeneous group of patients, some of whom have a predominantly psychological etiology, whereas others have a predominantly biological etiology, and that the presence of multiple comorbid disorders is a marker for psychological influences on etiology.

Colonic Diseases, Functional↗

PubMed2000

Physiological and symptom determinants of exercise performance in patients with chronic airway obstruction.

To evaluate the physiological and symptom determinants of exercise performance (EP) as measured by a 6-min walking test (6MWD), Watt(max), and peak oxygen consumption (VO2 ml/min/kg), 105 patients with chronic airway obstruction (CAO) [50 chronic obstructive pulmonary disease (COPD): 44 men, aged 63+/-7 years, forced expiratory volume in 1 sec (FEV1) forced vital capacity (FVC)(-1)% 54+/-13; and 55 asthmatic: 23 men, aged 55+/-10 years, FEV1 FVC(-1) % 65+/-10] underwent evaluation of 6MWD, symptom limited cyclo-ergometer exercise test, spirometry, respiratory muscle function, arterial blood gases and sensation of dyspnoea [using the Borg scale, Visual Analogue Scale (VAS) and Baseline Dyspnoea Index (BDI)]. A hierarchical method of analysis identified the residual volume (RV), total lung capacity (TLC)(-1) ratio, BDI and the patient's age as the strongest and most consistent correlates of EP (r2 = 0.14-0.21). The correlation between EP and its various determinants was not influenced by diagnosis. The relationship between breathlessness and EP was different between men and women: at any given level of exercise, women were more breathless than men. In multivariate analyses that contained both RV TLC(-1) and BDI, the RV TLC(-1) ratio was the strongest correlate of EP, although the BDI remained a significant covariate. Overall, age was the major determinant of EP but inclusion of the RV TLC(-1) ratio and the BDI into the model explained a further 9-15% of the variance in EP. These three covariates together explained 26-34% of the variance between patients. We conclude that in stable CAO patients, the prediction of exercise capacity by anthropometric, demographic, clinical and physiological variables is likely to be low. Age, pulmonary hyperinflation and dyspnoea are the strongest and most consistent correlates of impaired exercise performance. Airways obstruction, measured during expiration using FEV1, does not appear to be a predictor of physiological impairment. These results underline the importance of performing exercise evaluation in CAO patients.

Aged↗

PubMed2000

The impact of health status on waiting time for major joint arthroplasty.

This study was conducted to determine the impact of health status on waiting time for major joint arthroplasty in a universal publicly funded health system. Data were collected prospectively from a cohort of 553 patients waiting for total hip or total knee arthroplasty. The WOMAC and SF-36 health status instruments were administered at the time the patient was placed on the waiting list. The outcome measure was length of waiting time. Multivariate analyses found increased body mass index and decreased social function as the only determinants of waiting time. This model explained only 4% of the variance in waiting time. The association between health status and waiting time for arthroplasties appears to be small. These findings suggest that major joint arthroplasty is not prioritized on the basis of burden of illness.

Adult↗

PubMedDate not supplied

[Duration of inpatient depression treatment--fair benchmarking between hospitals].

Process and outcome quality of inpatient treatment of depression in Germany was described in a multicenter study of 10 hospitals in North-Rhine Westphalia, Baden-Württemberg and Bavaria. The treatment of more than 2000 depressive patients was assessed by quality indicators and outcome was compared between the hospitals (benchmarking). Results show great variance in length of stay between the hospitals. While in one hospital patients with depressive episodes were discharged after 36.8 days (average), the average length of stay in another hospital was 64.3 days. Furthermore the study revealed that hospitals differ strongly regarding their case-mix. Using stepwise multiple regression analyses potential confounding variables (sociodemographics, history of previous treatment, severity of depression) were identified and their influence on length of stay was calculated. After cross validation the regression analyses model explained 7% of the variance and included 5 predictors. Length of stay is prolonged by patients with a recurrent depressive disorder, by patients with impairment of social functioning and by severity of the depression. Length of stay is reduced if the indication of inpatient treatment was crisis intervention and if there was a previous suicide attempt. It was shown that differences in patient case-mix only account for a small percentage of hospital differences in length of stay. Method, effort and benefit of the regression analyses approach are discussed.

Adult↗

PubMed2004

Vibrational delocalization in ammonia aerosol particles.

The present contribution investigates shape effects and surface effects in the infrared spectra of pure (NH(3)) and mixed (NH(3)-CO(2) and NH(3)-NH(2)D-NHD(2)-ND(3)) ammonia particles with sizes between about 1 and 50 nm. The particles investigated have been generated in a collisional cooling cell as aerosols at temperatures between 20 and 80 K. The contribution reveals that only the combination with a microscopic model leads to a comprehensive understanding of the various features observed in the experimental infrared spectra. As one of the major results, the corresponding exciton model explains why pronounced shape effects observed for pure particles only play a minor role in the case of mixed particles.

Journal Article↗

PubMed2005

Nuclear magnetic resonance and dielectric investigations of molecular motions in a glassy crystal: the mixed compound (CN-adm)0.75(Cl-adm)0.25.

The dynamic properties of plastic crystalline mixed adamantane's derivatives namely cyanoadamantane (75%) and chloroadamantane (25%) were investigated by dielectric and nuclear magnetic resonance (NMR) spectroscopy, covering a spectral range of 12 decades in the temperature range 110-420 K. Phase transformations were studied and dynamical parameters of the plastic (I), glassy (Ig), and ordered (III) phases were determined and compared with those of pure compounds. The dynamics of the supercooled plastic phase is characterized by an alpha-process exhibiting an Arrhenius behavior which classified the mixed compound as a strong glass former. In the plastic phase, NMR relaxation times were interpreted by using a Frenkel model, which takes into account structural equilibrium positions. This model explains adequately the experimental results by considering two molecular motions. In both the glassy state and plastic phase the motional parameters agree with those of 1-cyanoadamantane. On the contrary, in the ordered phase, the motional parameters related to the uniaxial rotation of chloroadamantane molecules indicate an accelerated motion.

Journal Article↗

PubMed2006

Crystal-liquid crystal binary phase diagrams.

We propose a new theoretical scheme for the binary phase diagrams of crystal-liquid crystal mixtures by a combination of a phase field model of solidification, the Flory-Huggins theory for liquid-liquid mixing and Maier-Saupe-McMillan (FH-MSM) model for nematic and smectic liquid crystal orderings. The phase field theory describes the crystal phase transition of anisotropic organic crystal and/or side chain liquid crystalline polymer crystals while the FH-MSM model explains isotropic, nematic and smectic-A phase transitions. Self-consistent calculations reveal several possible phase diagram topologies of the binary crystal-liquid crystal mixtures. The calculated phase diagrams were found to accord well to the reported experimental results.

Journal Article↗

PubMed2004

Association between climate variability and malaria epidemics in the East African highlands.

The causes of the recent reemergence of Plasmodium falciparum epidemic malaria in the East African highlands are controversial. Regional climate changes have been invoked as a major factor; however, assessing the impact of climate in malaria resurgence is difficult due to high spatial and temporal climate variability and the lack of long-term data series on malaria cases from different sites. Climate variability, defined as short-term fluctuations around the mean climate state, may be epidemiologically more relevant than mean temperature change, but its effects on malaria epidemics have not been rigorously examined. Here we used nonlinear mixed-regression model to investigate the association between autoregression (number of malaria outpatients during the previous time period), seasonality and climate variability, and the number of monthly malaria outpatients of the past 10-20 years in seven highland sites in East Africa. The model explained 65-81% of the variance in the number of monthly malaria outpatients. Nonlinear and synergistic effects of temperature and rainfall on the number of malaria outpatients were found in all seven sites. The net variance in the number of monthly malaria outpatients caused by autoregression and seasonality varied among sites and ranged from 18 to 63% (mean=38.6%), whereas 12-63% (mean=36.1%) of variance is attributed to climate variability. Our results suggest that there was a high spatial variation in the sensitivity of malaria outpatient number to climate fluctuations in the highlands, and that climate variability played an important role in initiating malaria epidemics in the East African highlands.

Africa, Eastern↗