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At least 721 records · Page 40Linked to original sources

Ant navigation en route to the goal: signature routes facilitate way-finding of Gigantiops destructor.

We investigated in laboratory conditions how foragers of the tropical ant Gigantiops destructor develop individually distinctive landmark routes. Way-finding along a familiar route involved the recognition of at least two locations, nest and feeding site, and the representation of spatial relations between these places. Familiar visual landmarks were important both at the beginning and at the end of the foraging journey. A motor routine guided the ants at the start of their foraging path towards the first landmarks, which they learnt to pass consistently on the same side, before taking the next direction. At the last stage of the route, landmark recognition allowed them to pinpoint their preferred feeding site without using distant cues or odometric information. By contrast, ants en route to the goal were not systematically guided by a stereotyped sequence of snapshots recalled at each corresponding stage of the route. Each ant slalomed in an idiosyncratic distinctive way around different midway landmarks from a foraging excursion to the next, which induced a variability of the path shapes in their intermediate parts. By reducing the number of landmark recognition-triggered responses, this economical visuomotor strategy may be helpful in the Amazonian forest where many prominent landmarks are alike.

Animals↗

Serum high density lipoprotein cholesterol in patients with abnormal coronary arteries.

Previous studies showing the inverse relationship between high density lipoprotein cholesterol (HDL-C) and coronary artery disease were based on myocardial infarction survivors and presumably normal subjects. To determine whether a similar relationship exists between patients with abnormal coronary arteries (ACA) and those with normal coronary arteries (NCA), the serum HDL-C and other lipoproteins of these patients and those of a group of presumably healthy control subjects (CTL) were determined. The ACA males had lower HDL-C and % HDL-C but higher TG, VLDL-TG, LDL-C/HDL-C and VLDL-C/HDL-C than the NCA and CTL males. They also had higher VLDL-C and % VLDL-C than the CTL males. Adjustment of HDL-C for serum TG eliminated the difference in HDL-C between the ACA and NCA groups but that between ACA and CTL groups remained. The ACA females had lower % HDL-C than the NCA and CTL females. They also had lower HDL-C but higher LDL-C/HDL-C and VLDL-C/HDL-C than the CTL females. The NCA and CTL groups did not differ in any of the lipid variables, although the NCA group values were intermediate to those of the ACA and CTL groups. Using various lipoprotein profiles, it was possible to classify the patients into the 3 groups.

Adult↗

Cytotoxic effect of T-2 mycotoxin on cells in culture as determined by a rapid colorimetric bioassay.

We developed a colorimetric assay for determining metabolic activity (viability) of cells exposed to toxic agents. This system is based on the ability of mitochondrial enzymes in viable cells to modify a tetrazolium salt into a blue formazan product that can be detected spectrophotometrically at 570 nm. The assay works equally well for mammalian and insect cell lines and at 48 hr color formation is linear over a cell input range of 1.56-50 X 10(4) cells/ml. The inhibitory effects of T-2 mycotoxin on tetrazolium cleavage in L929 cells is comparable to that observed for protein and DNA synthesis (50% inhibition = 6-8 ng/ml). Using this system to analyze the lethal effect of T-2 toxin on cells from various animal species, it was found that bovine cells were the most sensitive (50% inhibition at 2.2 ng/ml) while hamster cells were the most resistant (50% inhibition at 26.2 ng/ml). Murine cells exhibited intermediate sensitivity (50% inhibition at 10.9 ng/ml). Variable toxin susceptibility was also observed among different cell types. Lymphocytes were 3-fold more sensitive to the T-2 inhibitory effects than comparable tissue culture cell lines. These data indicate that the colorimetric assay system could have broad applications in toxicological studies. Further, the observed differences in species sensitivity may provide insight into the primary mechanism of the T-2 toxin-cell interaction that ultimately leads to cell death.

Animals↗

Thoracic aortic occlusion: somatosensory evoked potential monitoring and neurologic outcome in a canine model.

Somatosensory evoked potentials (SEPs) were monitored in 17 canines during spinal cord ischemia induced by balloon occlusion of the thoracic aorta. Graded distal aortic hypotension to 40 mmHg in seven animals had no significant effect upon the evoked potential. A significant alteration in the SEP did result in 21 +/- 9.8 minutes when distal aortic pressures were reduced in a graded fashion below 30 mmHg. Acute occlusion of the thoracic aorta (10 animals, distal pressure 15-25 mmHg) was associated with a change in the SEP in 8.4 +/- 4.3 minutes. Continuation of aortic occlusion for 30 minutes beyond an evoked potential change resulted in a moderate to severe motor deficit in all cases. Somatosensory evoked potentials obtained 72-96 hours after the ischemic injury were closely correlated with sensory deficits, but were not predictive of motor examination. Histologic examination of the spinal cords demonstrated central gray necrosis of the lumbar region in all animals with a severe deficit, and a variable degree of neuronal loss in the intermediate and dorsal gray matter zones in animals with moderate deficits. This balloon occlusion method is relevant as a model of spinal cord injury during aortic occlusion, such as may occur during aortic surgery.

Acute Disease↗

Rapid detection of common cytochrome P450 2D6 alleles in Caucasians.

CYP2D6 is a highly polymorphic enzyme that mediates the metabolism of around 20% of all currently prescribed drugs. Genetic variability within CYP2D6 results in poor (PM), intermediate (IM), extensive (EM) and ultra-rapid metabolisers (UM) of CYP2D6 substrates. Here we describe an assay which is able to detect the major PM (CYP2D6*3, *4, *5, *6), IM (CYP2D6*9, *10, *41) and UM (CYP2D6*nxn) alleles found in Caucasians. This assay is performed in two stages. The first stage is a multiplex long-range PCR which is used to simultaneously screen for whole gene deletions and duplications while isolating CYP2D6 from the CYP2D gene cluster to avoid pseudogene contamination. In the second stage, individuals with one or more copies of CYP2D6 are genotyped for PM and IM alleles using a two-tube multiplex Amplification Refractory Mutation System (ARMS). The specificity and reliability of the multiplex long-range PCR and subsequent ARMS were confirmed using a panel of positive controls that had been previously validated by PCR-RFLPs and DNA sequencing. This two-stage assay offers a robust and cheap alternative to many currently available CYP2D6 genotyping approaches. Our entire assay, once patient DNA has been extracted, can be run within 7 h using 10 microl PCRs.

Alleles↗

Cell wall biosynthesis: glycan containing oligomers in developing cotton fibers, cotton fabric, wood and paper.

A series of oligomeric glycans can be extracted from the cell walls of developing cotton fibers with weak acid. Glycans that produce similar profiles on high pH anion chromatography with pulsed amperometric detection (HPAEC-PAD) are also found in a protein complex extracted from developing fibers and in amorphous aggregates found in association with immature fibers in developing, but not in mature cotton bolls. The quantity and composition of the glycans recovered from the carbohydrate-protein complex varies significantly with the time of day when the bolls are harvested. This diurnal variation is consistent with the hypothesis that secondary cell walls are deposited primarily at night. Incubation of re-hydrated cotton fibers in the presence of exogenous oligosaccharides, myo-inositol and glycerol substantially alters the apparent quantity of the oligomers extracted from the fibers. The same and similar glycans have also been extracted from cotton fabric, marine algae, various paper products and wood. While many of the oligomers isolated from the various cellulose sources display the same peaks by HPAEC-PAD, the specific number of oligomers and their relative quantities appear unique for each source of cellulosic material. Oligomeric glycans, as described in the preceding, are present in all cellulose sources that have been investigated. Their relative abundance changes in response to source, stage of development and other physiological variables. We hypothesize that the glycans are intermediates in the biological assembly of cellulose, and that their incorporation in cellulose is mediated by physicochemical and enzymatic mechanisms.

Cell Wall↗

Vehicle effects on in vitro percutaneous absorption through rat and human skin.

We studied the effects of three vehicles (propylene glycol, octanol and ethyl decanoate) with differing polarity on the in vitro percutaneous absorption of three chemicals (fluazifop-butyl, dimethyl phthalate and fomesafen sodium salt) with a range of physico-chemical properties. Absorption rate measurements were made from high vehicle volume (200 microliters/cm2) and low vehicle volume (< 10 microliters/cm2) applications. For the lipophilic fluazifop-butyl absorption rate was highest from the more polar vehicle propylene glycol, but this effect was only significant under high-volume conditions. There was a variable vehicle effect on absorption of the intermediate chemical dimethyl phthalate. The largest vehicle effect was seen for the more hydrophilic fomesafen sodium salt where absorption was fastest from the least polar vehicle ethyl decanoate. These results support the hypothesis that the absorption process can in part be predicted from a knowledge of solute solubility. Vehicle effects were greater from high volume applications than from those more comparable to occupational exposure conditions.

Animals↗

Type I and II metabotropic glutamate receptor agonists and antagonists evoke cardiovascular effects after intrathecal administration in conscious rats.

1. In the present study, the role of metabotropic glutamate receptors (mGluRs) in central cardiovascular regulation in conscious rats was examined. To this end, agonists and antagonists for type I and II mGluRs were administered intrathecally, and the temporal changes in blood pressure and heart rate were recorded. 2. L-glutamate (1 micromol) and the prototypical mGluR agonist (1S,3R)-ACPD (0.1 and 0. 3 micromol) both increased mean arterial pressure (MAP) and heart rate (HR), implicating functional mGluRs in the spinal cord. The type I mGluR agonist DHPG (0.01 - 0.1 micromol) evoked increases in MAP (max=25+/-5 mmHg) and HR (max=88+/-23 beats min-1). The duration of action, but not the maximum effects, were dose-related and ranged from approximately 10 min to <90 min and 1 min to >90 min for MAP and HR, respectively. 3. The type I/II mGluR agonist CCG-1 (0.1 and 0. 3 micromol) caused smaller, variable increases in MAP and HR of intermediate duration (5 - 20 min), whereas the type II MGluR agonist APDC (0.1 and 1.0 micromol) caused marked, but transient (3 - 5 min), pressor and tachycardic responses. The highest doses of DHPG and CCG-1, but not APDC, also evoked behavioural responses similar to a spontaneous nociceptive behavioural effect reported previously. 4. The type I and II mGluR antagonists (AIDA and LY307452, respectively) were also given approximately 5 min before the administration of the respective type I and II mGluR agonists (DHPG and APDC). Both compounds caused pressor and tachycardic responses, with the effect of AIDA, but not LY307452, returning to control levels before mGluR agonist administration. AIDA significantly attenuated the overall cardiovascular effects of DHPG, while LY307452 significantly attenuated the overall cardiovascular effects of APDC. 5. These results indicate that functional type I and II mGluRs exist in the spinal cord, and that their activation evokes prolonged cardiovascular effects.

Animals↗

Pituitary carcinoma: an ultrastructural study of eleven cases.

Pituitary carcinomas are very rare. Defined as adenohypophysial tumors that undergo craniospinal and/or systemic metastasis, most are PRL- or ACTH-producing. Their ultrastructural features, particularly relative to benign adenomas of similar functional type, have not been sufficiently explored. Eleven cases of immunohistochemically characterized pituitary carcinoma with documented cerebrospinal and/or systemic metastases were collected from various institutions and studied by transmission electron microscopy. The tumors were surgically removed from 7 women and 4 men ranging in age between 28 and 74 years (mean, 50 years). All were endocrinologically functioning. Six tumors secreted PRL; three were ACTH-producing; one each was GH/PRL- and TSH-producing. The patients with the ACTH-producing tumors had all presented with Cushing's disease and two of them had undergone adrenalectomy (Nelson syndrome). In most cases significant cellular atypia and mitotic activity were observed. In terms of morphologic features of functional differentiation, electron microscopy revealed that in 9 cases the tumor cells maintained at least some ultrastructural markers of their basic phenotype. A unique feature in 2 ACTH carcinomas was the variable admixture of smooth endoplasmic reticulum with intermediate (cytokeratin) filaments. In 2 cases, both PRL-producing carcinomas, the cell type comprising the tumor could not be identified on an ultrastructural basis alone. Ultrastructural investigation of pituitary carcinomas confirms their endocrine nature and, in most but not all cases, reveals their functional differentiation. Despite the diagnostic utility of electron microscopy in the assessment of these rare tumors, the distinction of pituitary carcinoma from pituitary adenoma cannot be firmly made on ultrastructural grounds alone.

Adenoma↗

Quantification of JC virus DNA in the cerebrospinal fluid of patients with human immunodeficiency virus-associated progressive multifocal leukoencephalopathy--a longitudinal study.

In progressive multifocal leukoencephalopathy (PML) the JC virus (JCV) load in the cerebrospinal fluid (CSF) is discussed as a parameter for disease progression. To investigate the evolution of viral shedding into the CSF, the JCV DNA concentration was quantified by competitive polymerase chain reaction (PCR) in multiple CSF samples from prior to and during an unsuccessful intrathecal salvage therapy in 2 human immunodeficiency virus-infected patients with biopsy-proven PML. With continuous clinical progression the virus load varied considerably intra- and interindividually, ranging from nondetectable to 1.2x108 genome equivalents/10 microliter CSF. Whereas an overall increase during progressive disease was confirmed, the virus burden was either constant or fluctuated irregularly during the intermediate stage of disease. This shows a variability of viral shedding during active disease that must be taken into account when the JCV load is measured by quantitative PCR for both the diagnosis of PML and monitoring under investigational treatment.

AIDS-Related Opportunistic Infections↗

Principles of interpretation of coronary velocity and pressure tracings.

The development of quantitative angiography and the introduction of new techniques of intracoronary imaging cannot replace the functional methods for the assessment of stenosis severity. The measurement of the trans-stenotic pressure gradient and of the post-stenotic flow velocity using miniaturized sensors with guidewire technology offers an alternative to the conventional non-invasive methods which is applicable in the catheterization laboratory at the time of the interventional procedure. The complexity of the coronary circulation, however, limits the possibility of establishing simple cut-off criteria to identify the presence of a flow-limiting stenosis. For intermediate lesions, or in the presence of variable haemodynamic conditions, the accuracy of the assessment can be improved by the application of more complex indices, proposed and validated in the animal laboratory and based on the instantaneous relationship between pressure or pressure gradient and flow velocity.

Angioplasty, Balloon, Coronary↗

Interleukin 6 production by human proximal tubular epithelial cells in vitro: analysis of the effects of interleukin-1 alpha (IL-1 alpha) and other cytokines.

Proximal tubular epithelial cells (PTEC) from human renal tissue obtained from biopsy or nephrectomy were grown in monoculture and evaluated in vitro at passage 2-4 for interleukin 6 (IL-6) production in response to medium alone or to interleukin 1 alpha (IL-1 alpha), tumour necrosis factor alpha (TNF alpha), interleukin 2 (IL-2), interferon gamma (INF gamma) or lipopolysaccharide (LPS). IL-6 bioactivity was quantitated using the IL-6-dependent murine hybridoma cell line (B9) and expressed as IL-6 units/ml/10(5) PTEC. PTEC cell lines exposed to medium alone produced intermediate amounts of IL-6 with substantial variability between cell lines. Introduction of IL-1 alpha resulted in a dose- and time-dependent increase in IL-6 production by PTEC that was maximal at 1 ng/ml IL-1 alpha at 24 h. All PTEC cell lines showed an increased IL-6 production on exposure to IL-1 alpha varying from 1.3- to 24-fold increase over baseline production. This response was completely blocked by anti-rIL-1 alpha. No significant IL-6 production by PTEC could be induced by TNF alpha, IL-2, IFN gamma, or LPS over a broad dosage range. Cycloheximide inhibited IL-6 production without irreversible cell toxicity, indicating de-novo synthesis. IL-6 produced by PTEC had a molecular weight of 26-29 kDa as demonstrated by Western blot analysis. Using PCR analysis we could demonstrate upregulation by IL-1 alpha of IL-6 mRNA in a dose-response fashion, indicating that IL-1 alpha regulates IL-6 production at a pretranslational value of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Pharmacokinetics of etomidate, a new intravenous anesthetic.

Etomidate sulfate, 0.3 mg/kg, was administered intravenously to eight patients and venous blood samples were drawn at intervals for the subsequent 10 hours. Plasma etomidate was determined by mass fragmentography. Plasma concentrations were fitted to a triexponential equation consistent with a three-compartment open pharmacokinetic model. Mean (+/-SD) variables were: initial t1/2, 2.6 +/- 1.3 min; intermediate t1/2, 28.7 +/- 14.0 min; apparent elimination t1/2, 4.6 +/- 2.6 hours; volume of the central compartment, 23.2 +/- 11.41; total apparent volume of distribution, 4.5 +/- 2.21/kg; fraction of drug in the central compartment, 7 per cent; total plasma clearance, 860 +/- 230 ml/min. Total blood clearance was estimated to be 754 ml/min and hepatic clearance, 739 ml/min. The large apparent volume of distribution indicates considerable tissue uptake. The hepatic clearance, being about 50 per cent of hepatic blood flow, indicates that changes in hepatic blood flow or hepatic metabolism will have only moderate effects on etomidate disposition.

Adolescent↗

Metabolism of halothane in obese Fischer 344 rats.

Halothane is metabolized by an oxidative pathway to stable, nonvolatile end products, trifluoroacetic acid (TFAA) and bromide (Br-), and by reductive pathways to Br-and inorganic fluoride (F-). There is evidence that both oxidatively and reductively formed intermediates may produce hepatotoxicity, although the exact etiology of the fulminant hepatic necrosis seen in humans is unproven. Obese patients receiving volatile anesthetics exhibit higher serum anesthetic metabolite concentrations than do normal-weight patients, and thus might be at greater risk of hepatotoxicity because of higher concentrations of reactive intermediates from halothane metabolism. To eliminate the variables inherent in human clinical studies leading to confounding interpretation of data, this study determined the contributions of oxidative and reductive pathways to halothane metabolism in an animal model of human hypertrophic obesity, the most common form of human obesity. Eight pairs of obese (high-fat diet) and normal-weight (standard chow), male Fischer 344 rats were anesthetized with halothane for 4 h at an inspired concentration of 0.78%. Serum and urinary concentrations of TFAA, Br-, and F-were measured. Thirty-six hours following halothane anesthesia, mean serum TFAA concentrations peaked at 7.3 +/- 1.1 mM in obese rats and 4.7 +/- 0.7 mM in nonobese rats. TFAA urinary excretions during the 180-h period postanesthesia were 519 +/- 69 and 336 +/- 22 mumol, respectively. Peak serum Br- concentrations were 9.1 +/- 1.0 and 6.9 +/- 0.6 mM for obese and nonobese rats, respectively, and Br-urinary excretions were 127 +/- 30 and 79 +/- 14 mumol, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparative effects of different dihydropyridines on the expression of adhesion molecules induced by TNF-alpha on endothelial cells.

OBJECTIVE: Lacidipine has already been demonstrated to reduce the expression of some adhesion molecules induced by pro-oxidant signals on endothelial cells. In order to verify if this effect is a peculiarity of this molecule, or belongs to other dihydropyridinic compounds (DHPs), the activity of lacidipine was compared with that of lercanidipine, amlodipine, nimodipine and nifedipine. DESIGN AND METHODS: The compounds were incorporated in human umbilical vein endothelial cells (HUVECs) using native low-density lipoprotein as a carrier. The drug concentrations in HUVECs were measured by mass spectrometry. Human recombinant tumour necrosis factor-alpha was then incubated with HUVECs for 7 h at 37 degrees C for adhesion molecule expression. RESULTS: The cellular amount of lacidipine, lercanidipine and amlodipine was similar, while nimodipine and nifedipine were almost undetectable or undetectable, respectively. Lacidipine, at any concentration, determined a dose-dependent significant decrease of the expression of intercellular adhesion molecule-1 (ICAM-1) ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) VCAM-1 and E-selectin (P < 0.01). Lercanidipine and amlodipine determined variable decreases of adhesion molecules at the intermediate and highest concentrations. Nimodipine and nifedipine determined no effect on ICAM-1, VCAM-1 and E-selectin. The lowest IC50, i.e. the concentration determining the 50% reduction of ICAM-1, VCAM-1 and E-selectin expression was obtained with lacidipine for all the adhesion molecules considered (P < 0.01). CONCLUSIONS: It is concluded that the effect of the DHPs used in this study on adhesion molecule expression is determined first by their lipophilicity and then by their intrinsic antioxidant activity.

Cell Adhesion Molecules↗

Pharmacokinetics of intravenous immunoglobulin in very low birth weight neonates.

We studied the pharmacokinetics of single doses of intravenous immunoglobulin (IVIG) of 1000, 750 and 500 mg/kg administered to 21 neonates with birth weights from 750 to 1500 g. No adverse effects were detected. Mean pharmacokinetic values for the large, intermediate and small dose groups, respectively, were: elimination half-life, 19.6, 28.7 and 22.1 days; clearance, 5.2, 5.6 and 3.7 ml/kg/day; volume of distribution, 151, 255 and 130 ml/kg. Mean peak IgG concentrations in serum were 1826, 1476 and 1257 mg/dl for the large, intermediate and small dose groups, respectively. Mean IgG on post-infusion Days 1 to 28 were similar for the intermediate and small dose groups but were higher in the larger dose group. Both large and intermediate doses achieved larger increases in IgG over preinfusion values (delta IgG) than the small dose. The differences in delta IgG between the large and intermediate doses were less notable. The wide variability observed indicates that individualization of intravenous immunoglobulin dosage will be required in these patients.

Drug Combinations↗

Maternal Effects Govern Variable Dominance of Two Abscisic Acid Response Mutations in Arabidopsis thaliana.

Three abscisic acid (ABA)-controlled responses (seed dormancy, inhibition of germination by applied ABA, and stomatal closure) were compared in wild-type versus homo- and heterozygotes of two Arabidopsis thaliana ABA-insensitive mutants, abi1 and abi2. We found that sensitivity of seeds to applied ABA is partially maternally controlled but that seed dormancy is determined by the embryonic genotype. The effects of the abi1 and abi2 mutations on ABA sensitivity of seed germination ranged from recessive to nearly fully dominant, depending on the parental source of the mutant allele. This maternal effect disappeared during vegetative growth. Stomatal regulation in heterozygotes showed substantial variability, but the average water loss was intermediate between that of homozygous mutants and wild type.

Journal Article↗

Malignant histiocytosis: a histological and ultrastructural study of lymph nodes in six cases.

A morphological, histological, and ultrastructural investigation was carried out on a series of six cases of malignant histiocytosis observed between 1973 and 1977. All lymph nodes were obtained prior to treatment. The histological findings revealed that the proliferating cell type was in all cases represented by histiocytes of varying degrees of atypia and with consistent phagocytic activity. In four cases, the histiocytic cellular proliferation also showed some degree of cohesiveness and, in two cases, there was capsular invasion. In three cases blood vessel invasion by malignant cells could be seen within the lymph node and in the surrounding tissue. On electron microscopy the tumour cells of malignant histiocytosis appeared to be pleomorphic with three types of cells: undifferentiated cells, histiocytes with variable degrees of differentiation, and cells with intermediate features. In particular, nonphagocytic and actively phagocytic histiocytes could be identified. The histological and ultrastructural data further support the idea that malignant histiocytosis is a disease that is related to the neoplastic proliferation of moderately differentiated histiocytes and their precursors. The latter may undergo various transformations with either apparently benign or definitely atypical morphological features.

Adolescent↗