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PubMed1994

Application of existing design software to problems in neuronal modeling.

In this communication, we describe the application of the Valid/Analog Design Tools circuit simulation package called PC Workbench to the problem of modeling the electrical behavior of neural tissue. A nerve cell representation as an equivalent electrical circuit using compartmental models is presented. Several types of nonexcitable and excitable membranes are designed, and simulation results for different types of electrical stimuli are compared to the corresponding analytical data. It is shown that the hardware/software platform and the models developed constitute an accurate, flexible, and powerful way to study neural tissue.

Action Potentials↗
PubMed1999

EM field prediction inside lossy multilayer elliptic cylinders for biological-body modeling and numerical-procedure testing.

In this paper, a biological model made up of a multilayer elliptic cylinder is considered. This canonical scattering problem is solved by a recursive procedure, which has been generalized to the case of lossy materials by using the analytical properties of Mathieu functions. Although it is a simplified model, this stratified configuration may simulate better than circular cylinders the local behavior of biological subsystems. In addition, it represents an effective tool for producing analytical data for testing direct-scattering numerical codes in biomedical applications and for the evaluation of reconstruction procedures in medical imaging.

Animals↗
PubMedDate not supplied

Minds, modules, and meta-analysis.

Wellman and colleagues' meta-analysis of performance on the false-belief task is methodologically useful, but it does not lead to any theoretical progress concerning the nature of the mechanisms that underlie the existence and development of "theory of mind." In particular, the results of this meta-analysis are perfectly compatible with "early competence" accounts that posit a specific, innate, and possibly modular basis for theory of mind. The arguments presented by Wellman and colleagues against such views stem not from their meta-analytic data, but from mistaken assumptions regarding the requirements of such theories (e.g., that there exist manipulations that improve performance only, or to a greater degree, in young children). Contrary to what Wellman and colleagues claim, their meta-analysis, while consistent with conceptual change, does not lend any new support for such theories.

Child↗
PubMed2001

Relating amino acid sequence to phenotype: analysis of peptide-binding data.

We illustrate data analytic concerns that arise in the context of relating genotype, as represented by amino acid sequence, to phenotypes (outcomes). The present application examines whether peptides that bind to a particular major histocompatibility complex (MHC) class I molecule have characteristic amino acid sequences. However, the concerns identified and addressed are considerably more general. It is recognized that simple rules for predicting binding based solely on preferences for specific amino acids in certain (anchor) positions of the peptide's amino acid sequence are generally inadequate and that binding is potentially influenced by all sequence positions as well as between-position interactions. The desire to elucidate these more complex prediction rules has spawned various modeling attempts, the shortcomings of which provide motivation for the methods adopted here. Because of (i) this need to model between-position interactions, (ii) amino acids constituting a highly (20) multilevel unordered categorical covariate, and (iii) there frequently being numerous such covariates (i.e., positions) comprising the sequence, standard regression/classification techniques are problematic due to the proliferation of indicator variables required for encoding the sequence position covariates and attendant interactions. These difficulties have led to analyses based on (continuous) properties (e.g., molecular weights) of the amino acids. However, there is potential information loss in such an approach if the properties used are incomplete and/or do not capture the mechanism underlying association with the phenotype. Here we demonstrate that handling unordered categorical covariates with numerous levels and accompanying interactions can be done effectively using classification trees and recently devised bump-hunting methods. We further tackle the question of whether observed associations are attributable to amino acid properties as well as addressing the assessment and implications of between-position covariation.

Amino Acid Sequence↗
PubMed2006

The empirical basis of substance use disorders diagnosis: research recommendations for the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V).

AIMS: This paper presents the recommendations, developed from a 3-year consultation process, for a program of research to underpin the development of diagnostic concepts and criteria in the Substance Use Disorders section of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and potentially the relevant section of the next revision of the International Classification of Diseases (ICD). METHODS: A preliminary list of research topics was developed at the DSM-V Launch Conference in 2004. This led to the presentation of articles on these topics at a specific Substance Use Disorders Conference in February 2005, at the end of which a preliminary list of research questions was developed. This was further refined through an iterative process involving conference participants over the following year. RESULTS: Research questions have been placed into four categories: (1) questions that could be addressed immediately through secondary analyses of existing data sets; (2) items likely to require position papers to propose criteria or more focused questions with a view to subsequent analyses of existing data sets; (3) issues that could be proposed for literature reviews, but with a lower probability that these might progress to a data analytic phase; and (4) suggestions or comments that might not require immediate action, but that could be considered by the DSM-V and ICD 11 revision committees as part of their deliberations. CONCLUSIONS: A broadly based research agenda for the development of diagnostic concepts and criteria for substance use disorders is presented.

Diagnostic and Statistical Manual of Mental Disord↗
PubMed1995

Nail incorporation kinetics of terbinafine in onychomycosis patients.

Patients with toe-nail onychomycosis were treated with terbinafine (250 mg daily, n = 20) for either 6 or 12 weeks in a randomized double-blind study. Plasma and distal nail clippings were taken before initiation of therapy and 1, 6, 12, 18, 24, 36 and 48 weeks thereafter. Analytical data of terbinafine extracted from nail clippings or plasma were obtained by high-performance liquid chromatography (HPLC). Nail extracts and isolated HPLC terbinafine peaks were analysed using a combined gas chromatography-mass spectroscopy system (GC-MS) for unequivocal identification of the drug. Terbinafine could be detected in the distal nail in the majority of the patients within 1 week of starting therapy. Maximum terbinafine levels of 0.52 and 1.01 micrograms/g were measured after 18 weeks in the 6- and 12-week treatment groups, respectively. While plasma levels decreased rapidly after termination of therapy terbinafine was detected in the nails as long as 30 weeks (6 weeks treatment) and 36 weeks (12 weeks treatment) after termination of therapy at a range of 0.28-0.19 microgram/g. The drug concentrations measured at all time points are well above the minimum inhibitory concentration (MIC) for dermatophytes and other fungi. These data suggest that the drug reaches the nail plate rapidly and persists there for several months after cessation of active treatment.

Antifungal Agents↗
PubMed2006

Nutritional counselling: an intervention for HIV-positive patients.

AIM: This paper reports an investigation of the effectiveness of nutritional counselling as an intervention to improve health outcomes for HIV-positive patients in Ghana, West Africa. BACKGROUND: In Ghana, like many developing countries, more patients with HIV and AIDS die because of their poor nutritional status than from the disease itself. With the lack of highly active anti-retroviral therapy for most HIV-infected patients in developing countries, nutritional counselling about high protein diet can be an essential intervention to reduce weight loss and improve weight gain and survival outcomes. METHOD: We used secondary-analytic data collected in summer 2003. Recorded monthly weights of HIV-positive patients were obtained and analysed for 25 people, whose ages ranged from 21 to 60 years, with a mean of 39.4 years (sd = 10.13). RESULTS: HIV-positive patients responded favourably to nutritional counselling about protein dietary intake as an intervention to improve weight gain. Repeated measures showed a statistically significant weight gain (P = 0.008). CONCLUSION: In the absence of anti-retroviral therapy, high protein nutrition can be an effective intervention for HIV-positive patients in developing countries. The health and nutritional status of the patients can be improved through nutritious food, allowing them to lead longer and better quality lives.

Adult↗
PubMed1976

Investigation of the covalent bond structure of peptide-matrix systems by Edman degradation of support-fixed peptides.

Two model peptides Ala-Ser-Asp-Tyr-Leu and Ala-Ser-Glu-Tyr-Leu have been synthesized and coupled with an without protecting groups to the amino groups of polystyrene resins. The yield in the binding operation was 93-97% by using water-soluble carbodiimides as condensing reagents. Edman degradation of the products and quantitative estimation of the amino acid phenylthio-hydantoins, as well as amino acid analysis of the partially and completely degraded resins, showed about 7-10% of the fixed peptides not to be involved in the degradation procedure. That part of the material which was not involved in the Edman degradation during the first step also remained inactive in the following degradation operations. The analytical data presented in the paper explain not only the course of the Edman degradation of peptides linked via the side-chain carboxylic groups to the resin, but they also describe the chemical reactivity of the various carboxylic groups in the binding operation. 22% of the peptides are bound to the resin by side-chain carboxylic groups in the case of the aspartate-containing peptide, 26-27% in the case of the glutamate-containing peptide. 75-77% and 72-75% respectively of the peptides are fixed to the resin via the C-terminal carboxylic group. No more than 3% of the fixed material may be bound bifunctionally to the support.

Amino Acids↗
PubMed1981

Comparative study of levels of secondary processing in bulk mRNA from dry and germinating wheat embryos.

There has been no previous study of levels of secondary processing in the template-active RNA of dry seeds and embryos. Such information is needed to evaluate the role of transcription in changing the cell-free translational capacity of bulk RNA during early imbibition of water by dry wheat embryos [J. Biol. Chem. 255, 5969-5970 (1980)]. Although it probably contains a higher proportion of "hidden breaks' than bulk mRNA from imbibing embryos, bulk mRNA in dry wheat embryos is also "capped' by 7-methylguanosine at 5' termini, devoid of unmethylated "caps', methylated internally (N6-methyladenosine) and polyadenylated at 3' termini. In contrast to other developing systems, there is no evidence that there are signal changes in levels of secondary processing in the bulk mRNA populations which support change in cell-free translational capacity of RNA 1-5 h postimbibition of dry wheat embryos. Change in the pattern of protein synthesis 5-24 h postimbibition also takes place without signal changes in levels of secondary processing in template-active RNA. The analytical data are evaluated and discussed in terms of difficulties allied with comparative analyses of poly(A)-rich RNA from dry and imbibing embryos, the former being refractory to, and the latter being most easily analyzed by, labeling in vivo.

Adenosine↗
PubMed1987

'Lipoteichoic acid' of Bifidobacterium bifidum subspecies pennsylvanicum DSM 20239. A lipoglycan with monoglycerophosphate side chains.

The lipid macroamphiphile of Bifidobacterium bifidum subsp. pennsylvanicum DSM 20239 was extracted with phenol/water and purified by treatment with nucleases and hydrophobic interaction chromatography. From analytical data, the results of Smith degradation, hydrolysis with HF and methylation studies, the following structure is proposed: (formula; see text) where n and m are approximately 7-10 and 8-15, respectively. The monoglycerophosphate residues have the sn-glycero-1-phosphate configuration; 20-50% of them are substituted with L-alanine in ester linkage. The lipid anchor is most likely a galactosyldiacylglycerol, part of which carries a third fatty acid. This is the first example among gram-positive bacteria of a glycerophosphate-containing lipid macroamphiphile that carries the glycerophosphate residues as monomeric side chains on a lipoglycan. Further, it contains L-alanine in place of the D-alanine found in lipoteichoic acids.

Bifidobacterium↗
PubMed1988

14,15-Dihydroxy-5,8,10,12-eicosatetraenoic acid. Enzymatic formation from 14,15-leukotriene A4.

When 14C-labeled (14S, 15S)-14,15-trans-oxido-5,8-cis-10,12-trans-eicosatetraenoic acid (14,15-leukotriene A4) was incubated with cytosolic epoxide hydrolase purified from mouse liver, one major radiolabeled product appeared. The structure was assigned as (14R, 15S)-14,15-dihydroxy-5,8-cis-10,12-trans-eicosatetraenoic acid (14,15-DHETE), based on analytical data as well as enzyme mechanistic considerations. The formation of this compound was dependent on time and enzyme concentration and was abolished after heat treatment of the enzyme. The apparent Km and Vmax values at 37 degrees C were 11 microM and 900 nmol X mg-1 X min-1 respectively. This enzymatic hydrolysis of 14,15-leukotriene A4 represents an additional mode of formation for 14,15-DHETE, a compound previously found to modulate functions of human leukocytes.

Animals↗
PubMed2007

Proteomics analysis in lung cancer: challenges and opportunities.

Recent technological developments in proteomic analysis are bringing us new insights into the molecular classification of tumours. Although proteomic analysis in cancer profiling is still under development both in terms of the instruments used and the data analytical tools, this method has great potential advantages for the analysis of biospecimens of many types. Direct measurement of abnormally expressed or modified proteins in the tumour tissue and/or patient blood may be an effective approach for discovering new biomarkers. Proteomics has the significant advantage of being able to discern not only changes in expression levels but also in post-translational modifications. Thus, the proteomics approach to protein profiling and biomarker discovery uncovers biomarkers from a different viewpoint than microarray analysis. This review summarizes the range of proteomics technologies employed for cancer profiling, and how they have been used to derive new classification models for human lung cancer.

Biomarkers, Tumor↗
PubMed1976

The pharmacokinetic characteristics of beta-receptor antagonists in man--similarities and differences of clinical relevance.

The aliphatic partial structure common to the beta-receptor antagonists leads to similar products of their biotransformation. The main qualitative and quantitative differences of the metabolism of the compounds of this class, however, rest in the nature of their aromatic or heterocyclic substituents. The physico-chemical properties of the beta-blockers appear to be predominantly responsible for the extent of metabolic degradation and for the distribution in the body, especially for the binding to proteins. As a consequence of their different biological disposition the clinically relevant systemic bioavailabilities of the various beta-blockers from oral doses differ drastically. Practolol maintains an extreme position among all other compounds: It is most hydrophilic, it is not bound to proteins, it is metabolized least, but cleared renally in unchanged form to 85% of the dose. Despite its extremely high systemic bioavailability, relatively high daily doses were required for therapy. The receptor sensitivity for practolol has been rated 2 to 3 powers of 1- lower than of propranolol. Comparative pharmacokinetic assessment of beta-receptor antagonists requires quantitative analytical data in clinically representative groups of patients. This has been demonstrated by respective studies with oxprenolol. The intra- and inter-individual systemic bioavailability, the differential analysis of plasma and erythrocytes, the multiexponential elimination kinetics, and their possible dependence on the dose have been studied as clinically relevant pharmacokinetic characteristics. The continuing attempt of the pharmaceutical industry to optimize the properties of beta-blockers also has taken advantage of the slow release principle in oral dosage forms as shown by the example of oxprenolol. The beta-receptor antagonists belong to one of the youngest classes of pharmaceuticals. Pharmacokinetic and metabolic data for the different representatives of this class have been generated in different laboratories with different approaches and different techniques. Therefore, full comparative documentation is still incomplete.

Adrenergic beta-Antagonists↗
PubMed2005

Personality and daily experience revisited.

In this introduction to the Journal of Personality special issue devoted to "Advances in Personality and Daily Experience" we attempt to trace recent progress in the study of personality and daily life. We begin by comparing and contrasting the methods of daily experience research adopted by investigators who authored empirical articles in the 1991 and current special issues according to the mode, schedule, and sampling frame for data collection. We then compare data analytic strategies across the 14 years between the two special issues and conclude that although the nature of the questions addressed has not changed dramatically, newer analytic methods and associated software have enhanced our ability to answer these questions more precisely. Finally, we provide an overview of the special issue contributions organized around three broad themes: personal vulnerabilities and resources that predict reactions to everyday events, interpersonal manifestations of personality in daily experience, and how personality in daily life affects physical and mental health and relates to disease risk.

Adaptation, Psychological↗
PubMed1987

Evaluating the significance of minimal brain dysfunction--results of an epidemiological study.

An epidemiological field investigation of 399 8-yr-old children was unable to support basic assumptions of the clinical MBD concept (existence of a homogeneous syndrome, specific psychopathology, evidence of increased perinatal risks). Using a multi-level case definition procedure and factor-analytic data aggregation, nearly complete independence was found among the diagnostical levels of neurophysiology, neuropsychology and specific skills. Main results were replicated after the application of several alternative models of case definition and were further confirmed by data from a clinical sample. Present findings emphasize the necessity to reconsider the concept of MBD and its practical consequences.

Attention Deficit Disorder with Hyperactivity↗
PubMed1986

Comparative study of guanidino compounds in serum and brain of mouse, rat, rabbit, and man.

The levels of 12 guanidino compounds were determined in the serum and brain of mouse, rat, rabbit, and man using cation-exchange column chromatography with the fluorescence ninhydrin detection method. A comparative study of these compounds was made in the four groups studied, for serum and brain. In rabbit and man the different guanidino compounds were also determined in various brain regions. This study provides basic analytical data that could facilitate the interpretation of further biochemical and neurochemical studies dealing with guanidino compounds that are identified as being toxins in hyperargininemia and uremia.

Animals↗
PubMed1993

Opioid peptides in the rabbit carotid body: identification and evidence for co-utilization and interactions with dopamine.

The rabbit carotid body is a catecholaminergic organ that contains dopamine and norepinephrine in a proportion of nearly 5:1. Chronic (15 days) carotid sinus nerve denervation or superior cervical ganglionectomy did not modify the carotid body dopamine content (5-6 nmol/mg of protein, equivalent to 250 pmol per carotid body), but sympathectomy reduced by approximately 50% the norepinephrine content. The carotid body has also a very high content of opioid activity (250 equivalent pmol of Leu-enkephalin/mg of protein) as measured by a radioreceptor assay that detects preferentially delta-opioid activity. In the carotid body the degree of opioid posttranslational processing to low-molecular-weight peptides (mostly Leu- and Met-enkephalin) is nearly 80%. HPLC identification of opioid peptides revealed that the sequences of Met- and Leu-enkephalin were in a proportion of nearly 6:1, indicating that the main opioid precursor in the carotid body is proenkephalin A. Chronic denervations of the carotid body did not modify the levels or the degree of opioid precursor processing. Acute hypoxic exposure of the animals (8% O2 in N2; 3 h) resulted in a parallel decrease of dopamine and opioid activity, without any change in the degree of opioid processing. Norepinephrine levels were not affected by hypoxia. These findings suggest corelease of dopamine and opioids during natural hypoxic stimulation. In agreement with the analytical data, [D-Ala2, D-Leu5]enkephalin, but not [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin, reduced the in vitro release of dopamine induced by low PO2, a high external K+ concentration, and dinitrophenol. Naloxone augmented the release response elicited by low PO2 stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Influence of obesity on the appearance of proteinuria and renal insufficiency after unilateral nephrectomy.

BACKGROUND: Some patients develop proteinuria and progressive renal failure after unilateral nephrectomy, although the majority of patients maintain normal renal function. Reasons to explain this different evolution are not known. METHODS: A cross-sectional study was performed in 73 patients who had undergone unilateral nephrectomy 13.6 +/- 8.6 years before. Patients with morphologic abnormalities in the remaining kidney, systemic disorders, or abnormal renal function at the time of nephrectomy were excluded. All of the 73 included patients showed normal renal function and negative proteinuria at nephrectomy. The patient's medical records were reviewed, and clinical and analytical data throughout follow-up were obtained. RESULTS: Fifty-three out of the 73 patients (group I) showed a normal renal function and negative proteinuria at the cross-sectional study. The remaining 20 patients (group II) showed proteinuria (3.4 +/- 3.1 g/day). The time elapsed between nephrectomy and proteinuria appearance was 10.1 +/- 6.1 years. Thirteen patients of group II had developed renal insufficiency (serum creatinine at the cross-sectional study of 3.9 + 3.2 mg/dL) in addition to proteinuria. The time elapsed between proteinuria appearance and the onset of renal insufficiency was 4.1 +/- 4.3 years. Renal insufficiency showed a slowly progressive course in most of these patients. There were no significant differences between group I and group II patients in age, gender, renal function, or blood pressure at the time of nephrectomy. In contrast, group II patients showed a body mass index (BMI) that was significantly higher than group I at nephrectomy (31.6 +/- 5.6 vs. 24.3 +/- 3.7 kg/m(2), P < 0.001), at cross-sectional study (33.3 +/- 6.6 vs. 25.1 +/- 3.5 kg/m(2), P < 0.001), and throughout follow-up. Among the 14 obese (BMI > 30 kg/m(2)) patients at the time of nephrectomy, 13 (92%) developed proteinuria/renal insufficiency. In contrast, among the 59 patients with BMI < 30 kg/m(2), only 7 (12%) developed these complications (P < 0.001). Kaplan-Meier estimated probability of negative proteinuria and normal renal function 10 years after nephrectomy was 40 and 70%, respectively, in obese patients at nephrectomy. At 20 years after nephrectomy, these percentages were 8 and 35%, respectively. In contrast, in nonobese patients, the probability of negative proteinuria and normal renal function was 93 and 98%, respectively, at 10 years (P < 0.001) and 77 and 91%, respectively, at 20 years (P < 0.001). Multiple logistic regression analysis showed that the risk of developing renal disease was only statistically correlated with BMI at the time of unilateral nephrectomy (odds ratio 1.34, 1.03 to 1.76 CI). CONCLUSIONS: Obese patients are at risk for developing proteinuria and chronic renal failure after unilateral nephrectomy. Regular and long-term follow-up are recommended in these patients.

Acute Kidney Injury↗