Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Intermediate Variables”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources

Golgi-like immunostaining of pituicytes and tanycytes positive for glial fibrillary acidic protein in the neurohypophysis of the Mongolian gerbil (Meriones unguiculatus).

Glial cells that contain the glial fibrillary acidic protein (GFAP; the major protein constituent of glial filaments) were stained immunohistochemically in thick frozen sections of the neurohypophysis of the Mongolian gerbil (Meriones unguiculatus). The resulting Golgi-like images provided informations on cytological features and distributional patterns of tanycytes and pituicytes. In the proximal median eminence, numerous bundled processes of tanycytes were revealed. They emerged from the ependymal and sub-ependymal layer and mostly reached the brain surface. Several tanycytic processes extended into the anatomical neural stalk. In the whole neural lobe, a dense network of GFAP-immunoreactive pituicyte processes was visualized. Stained pituicytes were highly asymmetric and exhibited a great morphological variability. Immunopositive fibers which were encountered in the intermediate lobe might be derived from pituicytes. Electron-microscopically further evidence was obtained that GFAP-positive pituicytes correspond to filament-rich fibrous pituicytes at the ultrastructural level.

Animals↗

Noninvasive identification of severe coronary artery disease using exercise tomographic thallium-201 imaging.

The ability of exercise thallium-201 tomographic imaging to predict the presence of left main or 3-vessel coronary artery disease (CAD) was examined in 688 patients who underwent both exercise thallium-201 testing and coronary angiography. Significant differences existed for multiple variables between patients with (n = 196) and without (n = 492) severe left main or 3-vessel CAD. Logistic regression analysis identified 4 variables as independently predictive of left main or 3-vessel CAD. These variables were the magnitude of ST-segment depression with exercise, the number of visually abnormal short-axis thallium-201 segments, the presence or absence of diabetes mellitus, and the change in systolic blood pressure with exercise. Using these variables, patients were classified by nomograms into low-, intermediate- and high-probability groups. Patients at high probability (n = 205) had a 52% prevalence of 3-vessel or left main CAD, whereas those at low probability (n = 170) had only a 12% prevalence. Only 53 patients (29%) with 3-vessel or left main CAD had perfusion abnormalities in all 3 coronary territories. Clinical and exercise parameters provide important independent information in the identification of left main or 3-vessel CAD by exercise thallium-201 tomographic imaging, because thallium scintigraphy alone is suggestive of extensive CAD in few patients.

Aged↗

Actions of guanidine hydrochloride on cat spinal monosynaptic reflex transmission.

The effects of a single intravenous dose of guanidine hydrochloride were examined on the function of the lumbar dorsal-ventral root and triceps surae nerve-ventral root monosynaptic reflex (MSR) in unanesthetized acute spinal (C-1 sectioned) cats. Guanidine, in a dose of 25 mg/kg, consistently depressed the amplitude of the monosynaptic reflex response while a dose of 200 mg/kg always exerted a facilitatory action. Intermediate doses of 50 or 100 mg/kg produced variable actions on the amplitude of the monosynaptic reflex from one preparation to another. The differential effects of guanidine on the evoked monosynaptic reflex are postulated to represent the ability of the drug to enhance both excitatory and inhibitory transmission, the latter predominating at smaller doses and the former becoming apparent with an increasing dose of guanidine. The facilitatory and the depressant effects of guanidine on the function of spinal reflexes were slow to develop, suggesting an intracellular site of action. These results may have significance for an understanding of the possible efficacy of guanidine in motor neuron disease in man.

Animals↗

Successful cryopreservation of Brugia pahangi third-stage larvae in liquid nitrogen.

Experiments are described which lead to the retention of infectivity of Brugia pahangi third-stage larvae after cooling to -196 degrees C. Methanol, a well documented cryoprotectant was used at a concentration of 20% (v/v). The schedule consisted of a 5 degrees C min-1 cool to an intermediate temperature of -21 degrees C and a subsequent rapid cool into liquid nitrogen. A rapid thaw of the parasites led to approximately 34% of motile cryopreserved larvae developing in multimammate rats (Mastomys natalensis) compared to unfrozen control larvae. Cooling rate and intermediate temperature were both found to be crucial variables affecting survival levels of the larvae.

Animals↗

Evaluation of the effect of ototopical neomycin on spiral ganglion cell density in the guinea pig.

The development of a reproducible unilateral deafness animal model was the primary objective of this study. Because of its importance in the function of cochlear prostheses, the status of the VIIIth nerve was used as the measure of deafness. The effect of a concentrated neomycin solution applied locally to the middle ear of the guinea pig was evaluated. Spiral ganglion cell survival was quantitated at 1, 2, 4, 6 and 10 weeks after exposure. Although the intermediate time periods showed moderate inter-animal variability, by ten weeks, consistent spiral ganglion cell loss was seen with maximum cell loss at the extreme apex (18.8% of control) and base (30.3% of control) and maximum cell survival in the lower middle turns of the cochlear spiral (53% of control).

Animals↗

Antimicrobial resistance of Enterococci in Lebanon.

There is little information on the types of Enterococcus spp and their antibiotic resistance patterns in Lebanon. One hundred and fifty-three consecutive clinical enterococcal isolates collected between 1998 and 1999 were tested against 11 antimicrobial agents using disk diffusion and the Etest. The isolates were identified by conventional methods and API-Strep and were found to consist of Enterococcus faecalis (72.5%), Enterococcus faecium (22.9%), Enterococcus avium (3.2%) and Enterococcus gallinarum (1.3%). The percent of resistant strains of E. faecalis and E. faecium respectively were, ampicillin 0.9 and 14%, erythromycin 59% and 40%, tetracycline 72% and 34%, chloramphenicol 32 and 11%, rifampin 36% and 57%, ciprofloxacin, 23% and 34%, norfloxacin 22 and 8%. High level aminoglycoside (HLA) resistance was found in 19% E. faecalis and 9% E. faecium for gentamicin and 36% and 26% for streptomycin. Excellent correlation was observed between the high level disk tests and the Etest in the detection of HLA resistance but not with the regular disks. None of the isolates showed resistance to vancomycin or teicoplanin except for one E. gallinarum isolate which showed intermediate resistance (MIC 16 mg/l) to vancomycin. These variable antimicrobial rates of resistance suggest a surveillance programme for antimicrobial resistance in this country would be helpful to help control infection, guide empirical antibiotic therapy and implement a policy of antibiotic usage.

Aminoglycosides↗

Comparative characterization of CHCl(3) metabolism and toxicokinetics in rodent strains differently susceptible to chloroform-induced carcinogenicity.

A comparative kinetic study in B6C3F1 mice, Osborne-Mendel (OM) and Sprague-Dawley (SD) rats has been undertaken with the major aim to determine the extent of covalent binding of chloroform reactive metabolites produced in vivo through oxidative and/or reductive metabolism in the target organs of chloroform carcinogenicity. Some additional kinetic observations of chloroform biotransformation were also collected comparatively. Expiration of [14C]-CO(2) showed that chloroform metabolism went to saturation in all tested rodent strains. In the B6C3F1 mouse maximal rates of approximately 135 µmol [14C]-CO(2)/kg b.w./h were reached at a dose of approximately 150 mg/kg, while in the two rat strains saturation occurred at a dose of approximately 60 mg/kg, with a maximal rate of approximately 40 µmol [14C]-CO(2)/kg b.w./h. At doses of 150-180 mg/kg b.w., limited differences were found in the distribution and elimination of [14C]-chloroform in the liver and kidney. Species differences have been found in the kinetics of alkali-extractable radioactivity in the blood. The levels of adducts of electrophilic intermediates with the polar heads (PH) of phospholipids (PL) showed a limited variability accross the rodents tested and did not correlate with the species and organ susceptibility to chloroform carcinogenicity. The levels of adducts of radical intermediates with the fatty acyl chains (FC) of PL were much lower than the PH adducts in all the samples analyzed; at the carcinogenicity bioassay doses, statistically significant levels of hepatic FC adducts were present only in the B6C3F1 mouse, where chloroform is hepatocarcinogenic. The observations in the rat kidney were suggestive of the formation of electrophilic reactive metabolites, presumably different from phosgene and associated with an initial chloroform reduction.

Journal Article↗

Multivariate genetic analysis of brain structure in an extended twin design.

The hunt for genes influencing behavior may be aided by the study of intermediate phenotypes for several reasons. First, intermediate phenotypes may be influenced by only a few genes, which facilitates their detection. Second, many intermediate phenotypes can be measured on a continuous quantitative scale and thus can be assessed in affected and unaffected individuals. Continuous measures increase the statistical power to detect genetic effects (Neale et al., 1994), and allow studies to be designed to collect data from informative subjects such as extreme concordant or discordant pairs. Intermediate phenotypes for discrete traits, such as psychiatric disorders, can be neurotransmitter levels, brain function, or structure. In this paper we conduct a multivariate analysis of data from 111 twin pairs and 34 additional siblings on cerebellar volume, intracranial space, and body height. The analysis is carried out on the raw data and specifies a model for the mean and the covariance structure. Results suggest that cerebellar volume and intracranial space vary with age and sex. Brain volumes tend to decrease slightly with age, and males generally have a larger brain volume than females. The remaining phenotypic variance of cerebellar volume is largely genetic (88%). These genetic factors partly overlap with the genetic factors that explain variance in intracranial space and body height. The applied method is presented as a general approach for the analysis of intermediate phenotypes in which the effects of correlated variables on the observed scores are modeled through multivariate analysis.

Adult↗

Simple rules yield complex food webs.

Several of the most ambitious theories in ecology describe food webs that document the structure of strong and weak trophic links that is responsible for ecological dynamics among diverse assemblages of species. Early mechanism-based theory asserted that food webs have little omnivory and several properties that are independent of species richness. This theory was overturned by empirical studies that found food webs to be much more complex, but these studies did not provide mechanistic explanations for the complexity. Here we show that a remarkably simple model fills this scientific void by successfully predicting key structural properties of the most complex and comprehensive food webs in the primary literature. These properties include the fractions of species at top, intermediate and basal trophic levels, the means and variabilities of generality, vulnerability and food-chain length, and the degrees of cannibalism, omnivory, looping and trophic similarity. Using only two empirical parameters, species number and connectance, our 'niche model' extends the existing 'cascade model and improves its fit ten-fold by constraining species to consume a contiguous sequence of prey in a one-dimensional trophic niche.

Ecology↗

CYP3A4 drug interactions: correlation of 10 in vitro probe substrates.

AIMS: Many substrates of cytochrome P450 (CYP) 3A4 are used for in vitro investigations of drug metabolism and potential drug-drug interactions. The aim of the present study was to determine the relationship between 10 commonly used CYP3A4 probes using modifiers with a range of inhibitory potency. METHODS: The effects of 34 compounds on CYP3A4-mediated metabolism were investigated in a recombinant CYP3A4 expression system. Inhibition of erythromycin, dextromethorphan and diazepam N-demethylation, testosterone 6beta-hydroxylation, midazolam 1-hydroxylation, triazolam 4-hydroxylation, nifedipine oxidation, cyclosporin oxidation, terfenadine C-hydroxylation and N-dealkylation and benzyloxyresorufin O-dealkylation was evaluated at the apparent Km or S50 (for substrates showing sigmoidicity) value for each substrate and at an inhibitor concentration of 30 microM. RESULTS: While all CYP3A4 probe substrates demonstrate some degree of similarity, examination of the coefficients of determination, together with difference and cluster analysis highlighted that seven substrates can be categorized into two distinct substrate groups. Erythromycin, cyclosporin and testosterone form the most closely related group and dextromethorphan, diazepam, midazolam and triazolam form a second group. Terfenadine can be equally well placed in either group, while nifedipine shows a distinctly different relationship. Benzyloxyresorufin shows the weakest correlation with all the other CYP3A4 probes. Modifiers that caused negligible inhibition or potent inhibition are generally comparable in all assays, however, the greatest variability is apparent with compounds causing, on average, intermediate inhibition. Modifiers of this type may cause substantial inhibition, no effect or even activation depending on the substrate employed. CONCLUSIONS: It is recommended that multiple CYP3A4 probes, representing each substrate group, are used for the in vitro assessment of CYP3A4-mediated drug interactions.

Cytochrome P-450 CYP1A1↗

Cell culture studies on human nerve sheath tumors.

The main controversy about nerve sheath tumors (NSTs) has been their histogenesis. A Schwann cell origin has been proposed by many investigators for both schwannomas and neurofibromas. However Erlandson and Woodruff observed that while schwannomas appeared to be composed predominantly of Schwann cells, neurofibromas consisted of mainly perineurial cells. In addition, variable numbers of fibroblast-like cells and intermediate cells also have been reported in the 2 lesions. Whether these represent distinct cell types or variants of Schwann cells is still debatable. In an attempt to solve this controversy, the present study was undertaken to observe the morphology and the behaviour of these tumors in culture. These studies showed that all nerve sheath tumors are basically of Schwann cell origin and that intermediate cells and fibroblasts are variants of Schwann cell. Tissue culture studies done chiefly on schwannomas showed that the morphological features of schwannomas are preserved in 'in vitro culture' condition and therefore the difference between neurofibroma and schwannoma appears to be due to inherent differentiating property of the Schwann cells along with some environmental stimulus.

Adolescent↗

Closed-form solution for the thermal dose delivered during single pulse thermal therapies.

This study provides a closed form, analytical expression for the thermal dose delivered by a single heating pulse. The solution is derived using the effective cooling method and the non-linear Sapareto-Dewey equation to determine the thermal dose delivered by the time-temperature history of a treatment. The analytical solutions are used to determine the optimal treatment conditions, i.e. those that exactly deliver the desired thermal dose at a specified time. For purposes of illustration, this study focuses on a 'conservative' clinical approach in which the desired thermal dose is delivered at the end of the 'cool down' period. The analytical results show that, after a clinical strategy has been chosen (e.g. conservative, aggressive or intermediate), the user can only specify two free variables for such an optimal treatment. Results are presented which suggest that a practical approach would be to specify both (1) the desired thermal dose to be delivered to the target (the clinically relevant outcome) and (2) the peak temperature to be reached (a measurable, clinically useful, patient dependent response variable that can be employed in feedback control systems); and then determine the associated, optimal heating magnitude and duration that need to be used to reach that dose and temperature. The results also reveal that, with a given patient condition and power deposition distribution (together specifying an effective cooling time constant for the treatment) and a specified thermal dose, there is a maximum allowable peak temperature that, if exceeded, will result in 'over-dosing' the heated tissue. The results also show that avoiding such non-optimal 'over-dosing' will be difficult in most high temperature therapies since, when high temperatures are produced in tissues, the temperature decay must be very fast in order to avoid over-dosing during the cooling period. Such rapid cooling can only occur if short effective cooling time constants are present-either as a result of large tissue blood flows in the patient or due to large conduction effects induced by the use of highly localized power deposition sources.

Humans↗

Is insulin resistance the cause of the metabolic syndrome?

Following up on original descriptions of clustering of cardiovascular risk factors (chiefly, glucose intolerance, dyslipidaemia and hypertension) around the presence of insulin resistance, the metabolic syndrome has recently been upgraded to the status of a disease entity with an inherent predictive value for cardiovascular disease. In pathophysiological terms, insulin resistance (of glucose metabolism) and the attendant compensatory hyperinsulinaemia are causally related to each of glucose intolerance, dyslipidaemia, high blood pressure and vascular dysfunction. The physiological mechanisms are concisely reviewed here. However, insulin resistance/hyperinsulinaemia alone is insufficient to cause these abnormalities, for which other pathogenic factors (e.g. ss-cell dysfunction for glucose intolerance) are required. The metabolic syndrome, on the other hand, has evolved from a set of statistical associations believed to carry an excess of cardiovascular risk. In the various existing definitions, a mixture of physical, metabolic and clinical variables have been used on grounds of predictive value or practical ease. These variables belong to different phenotypes, which are upstream, intermediate and proximal, respectively, in their relation to clinical disease. The resulting 'syndromes' usually lack a cogent conceptual structure, may reflect the particular data set from which they are extracted and may be of limited applicability. While overt diabetes, clinical hypertension and frank dyslipidaemia are often present together in the same patient, a subclinical syndrome with a distinct, probable aetiology and a proven power as a risk indicator remains to be identified.

Blood Glucose↗

Self-reported life satisfaction and 20-year mortality in healthy Finnish adults.

The authors investigated the role of self-reported life satisfaction in mortality with a prospective cohort study (1976-1995). A nationwide sample of healthy adults (18-64 years, n = 22,461) from the Finnish Twin Cohort responded to a questionnaire about life satisfaction and known predictors of mortality in 1975. A summary score for life satisfaction (LS), defined as interest in life, happiness, loneliness, and general ease of living (scale range, 4-20), was determined and used as a three-category variable: the satisfied (LS, 4-6) (21%), the intermediate group (LS, 7-11) (65%), and the dissatisfied (LS, 12-20) (14%). Mortality data were analyzed with Cox regression. Dissatisfaction was linearly associated with increased mortality. The age-adjusted hazard ratios of all-cause, disease, or injury mortality among dissatisfied versus satisfied men were 2.11 (95% confidence interval (CI): 1.68, 2.64), 1.83 (95% CI: 1.40, 2.39), and 3.01 (95% CI: 1.94, 4.69), respectively. Adjusting for marital status, social class, smoking, alcohol use, and physical activity diminished these risks to 1.49 (95% CI: 1.16, 1.92), 1.35 (95% CI: 1.01, 1.82), and 1.93 (95% CI: 1.19, 3.12), respectively. Dissatisfaction was associated with increased disease mortality, particularly in men with heavy alcohol use (hazard ratio = 3.76, 95% CI: 1.61, 8.80). Women did not show similar associations between life satisfaction and mortality. Life dissatisfaction may predict mortality and serve as a general health risk indicator. This effect seems to be partially mediated through adverse health behavior.

Adolescent↗

Antibiotic resistance of Neisseria gonorrhoeae in Spain: trends over the last two decades.

In vitro activities of six antimicrobial agents against 2966 strains of Neisseria gonorrhoeae, isolated in Spain between 1983 and 2001, were determined. The percentages of intermediately susceptible and resistant isolates to penicillin (MIC > or = 0.12 mg/L) and tetracycline (MIC > or = 0.5 mg/L) were very high over the period of study. Strains intermediately susceptible to cefoxitin were identified at a variable percentage during the study. All N. gonorrhoeae isolates were susceptible to spectinomycin and ceftriaxone. Recently, resistance to ciprofloxacin has emerged.

Anti-Bacterial Agents↗

Midgut basal lamina thickness and dengue-1 virus dissemination rates in laboratory strains of Aedes albopictus (Diptera: Culicidae).

Strain differences in midgut basal lamina thickness, assessed by measurement in transmission electron micrographs, and disseminated infection rates of dengue-1 virus were compared among three laboratory strains of Aedes albopictus (Skuse). Mean basal lamina thickness for the New Orleans and Houston strains were significantly greater than those for the Oahu strain, which exhibits a higher disseminated infection rate than the former two. Although basal lamina thickness among the F1 progeny of reciprocal crosses of the Oahu and Houston strains were intermediate between the parental strains, they were too variable to be useful as markers in genetic studies. Measurements of basal laminae among individuals of the New Orleans strain, with disseminated or nondisseminated infections, failed to demonstrate a role for basal lamina thickness as a modulator of dengue-1 virus dissemination across the midgut epithelium of Ae. albopictus.

Aedes↗

Does nondifferential misclassification of exposure always bias a true effect toward the null value?

The authors present some examples to demonstrate that in certain nondifferential misclassification conditions with polychotomous exposure variables, estimates of odds ratios for categories at intermediate level of risk can be biased away from the null or can change direction. In addition, the authors present two examples to demonstrate that the slope of the dose-response trend for the true distributions can change direction, creating a false inverse trend, even if the misclassification is nondifferential.

Bias↗

Role for nitrosative stress in diabetic neuropathy: evidence from studies with a peroxynitrite decomposition catalyst.

Nitrosative stress, that is, enhanced peroxynitrite formation, has been documented in both experimental and clinical diabetic neuropathy (DN), but its pathogenetic role remains unexplored. This study evaluated the role for nitrosative stress in two animal models of type 1 diabetes: streptozotocin-diabetic mice and diabetic NOD mice. Control (C) and streptozotocin-diabetic (D) mice were treated with and without the potent peroxynitrite decomposition catalyst FP15 (5 mg kg(-1) d(-1)) for 1 wk after 8 wk without treatment. Sciatic nerve nitrotyrosine (a marker of peroxynitrite-induced injury) and poly(ADP-ribose) immunoreactivities were present in D and absent in C and D+FP15. FP15 treatment corrected sciatic motor and hind-limb digital sensory nerve conduction deficits and sciatic nerve energy state in D, without affecting those variables in C. Nerve glucose and sorbitol pathway intermediate concentrations were similarly elevated in D and D+FP15 vs C. In diabetic NOD mice, a 7-day treatment with either 1 or 3 mg kg(-1) d(-1) FP15 reversed increased tail-flick latency (a sign of reduced pain sensitivity); the effect of the higher dose was significant as early as 3 days after beginning of the treatment. In conclusion, nitrosative stress plays a major role in DN in, at least, type 1 diabetes. This provides the rationale for development of agents counteracting peroxynitrite formation and promoting peroxynitrite decomposition, and their evaluation in DN.

Animals↗