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PubMed1996

Receptor-mediated effects on ligand availability influence relative mitogenic potencies of epidermal growth factor and transforming growth factor alpha.

Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) elicit quantitatively different cell proliferation responses even though they act via a common receptor, the epidermal growth factor receptor (EGFR). We hypothesized that differential cellular trafficking of available ligand is responsible for the different mitogenic responses elicited by EGF and TGF alpha. Mitogenesis and ligand depletion were determined simultaneously in NR6 mouse fibroblasts expressing either wild-type (WT) or internalization-deficient cytoplasmic domain-truncated (c'973) EGFR. Thus we could determine the effects of both ligand-induced and low level constitutive ligand/receptor processing. For a given initial amount of growth factor, TGF alpha is a weaker stimulus than EGF in cells expressing either form of the EGFR. This difference in the mitogenic potencies correlates with increased depletion of TGF alpha observed during the growth assays. When this difference in ligand depletion is accounted for, or minimized, EGF and TGF alpha elicit quantitatively similar growth responses. Therefore, the relative mitogenic potencies of EGF and TGF alpha depend on ligand availability, as determined by the cellular trafficking of these ligands in conjunction with environmental circumstances. Interestingly, our data demonstrate that TGF alpha can be a less potent mitogenic stimulus than EGF under conditions where ligand availability is limited. Further, in our assays, differences in ligand processing are sufficient to explain the different mitogenic potencies of these growth factors in either of the receptor trafficking scenarios. Our results suggest a model of regulation of hormone responsiveness which favors dissociative ligands (such as TGF alpha) in receptor-limited situations and non-dissociative ligands (such as EGF) in the face of high receptor levels.

Animals↗

PubMed1997

Mangabey (Cercocebus albigena) ranging patterns in relation to fruit availability and the risk of parasite infection in Kibale National Park, Uganda.

Two opposing hypotheses concerning determinants of mangabey (Cercocebus albigena) ranging patterns have been advocated. One hypothesis suggests that ranging patterns of mangabeys are largely a response to fruit availability, while the other hypothesis advocates that concerns of fruit availability are supplemented or overridden by concerns of fecal contamination and that the risk of parasite infection, especially during dry weather, determines their pattern of range use. In this 9 month study of mangabeys in the Kanyawara study area of Kibale National Park, mangabeys moved longer distances during the wet season than during the dry season. There were no seasonal differences in group spread, number of 50 by 50 m quadrats used, or in quadrat overlap between sequential sample periods. Intensity of quadrat use was closely related to the number of fruiting trees/lianas in the quadrats, irrespective of season. These findings are consistent with the hypothesis that fruit availability is a main factor influencing mangabey ranging patterns. The results are not consistent with the hypothesis that mangabey ranging patterns largely reflect differential seasonal risk of parasite infection.

Animals↗

PubMed1998

More physicians: improved availability or induced demand?

A number of empirical studies have shown that there is a negative association between population:physician ratio and utilization of medical services. However, it is not clear whether this relationship reflects supplier-inducement, the effect of lower prices on patient demand, a supply response to variation in health status, or improved availability. In Norway, patient fees and state reimbursement fees are set centrally. Therefore, the correlation between utilization and population:physician ratio either reflects supplier-inducement, a supply response or an availability effect. We applied a theoretical model which distinguished between an inducement and an availability effect. The model was implemented on a cross-sectional data set which contained information about patient visits and laboratory tests for all fee-for-service primary care physicians in Norway. Since population:physician ratio is potentially endogenous, an instrumental variable approach is used. We found no evidence for inducement either for number of visits or for provision of laboratory services.

Clinical Laboratory Techniques↗

PubMed2000

Change in food availability during pregnancy: Is it related to adult sudden death from cerebro- and cardiovascular disease in offspring?

Maternal access to food during pregnancy affects birth weight and other characteristics of offspring. It has been suggested that fluctuations in food availability during infancy, ranging from plentiful to starvation, may influence cerebro-cardiovascular risk factors for the offspring during adult life. This study was designed to test the correlation between food availability changes during life before birth and adult sudden death from disease. This was a follow-up study of ancient cohorts in the parish of Skellefteå, Sweden, comprising 7,572 individuals born between 1805 and 1849 and still alive at age 40. Food availability variations in the parish during their prenatal life were ascertained from historical sources, the main outcome measures being overall mortality and mortality from sudden death in the age range 40-70 years. The risk of sudden death was almost doubled for those whose mothers were struck by a poor harvest during the early stages of pregnancy, but who experienced a good harvest toward the end. Yet almost the same over-risk was evident for the converse case: plentiful food supply in early pregnancy followed by a poor harvest toward the end. A stable maternal access to food during pregnancy is important for the offspring's risk of sudden death from cerebro- and cardiovascular disease as an adult. Am. J. Hum. Biol. 12:447-453, 2000. Copyright 2000 Wiley-Liss, Inc.

Journal Article↗

PubMed2005

Effects of forest structure and composition on food availability for Varecia variegata at Ranomafana National Park, Madagascar.

We present a summary of a long-term field study that examined the effects of forest disturbance on the availability of palatable fruit and its utilization by V. variegata. Forest structure and tree species composition were measured in three adjacent study areas, with different histories of disturbance, in Ranomafana National Park (RNP), Madagascar. V. variegata abundance was monitored by frequent encounters with resident groups and periodic censuses conducted along trails. Finally, the abundance of mature fruit in species used by V. variegata was scored monthly at representative trees at several locations. V. variegata abundance was most consistent in the least anthropogenically disturbed site, while no established lemur groups were observed in the heavily logged site for over a decade post-harvest. Lemur abundance was variable in the selectively logged site. The presence of select food trees, particularly specimens with voluminous crowns capable of producing abundant fruit crops, appears to be key to the establishment and expansion of V. variegata groups. Our analysis of year-long fruit utilization revealed a high degree of preference for several species of trees. Two species exhibited mature fruit in a low percentage of stems but were available for a protracted period of time, while two additional species showed high intraspecific fruiting synchrony and were available for a shorter period of time. These contrasting phenologies, rather than the individual tree species, may be most important to V. variegata due to their coincident timing of fruit maturation with key lemur life-history events. Any disturbance-natural or anthropogenic-that disrupts the phenology cycles of food trees has the potential to impact lemur abundance and dispersion. Intense disturbances, such as heavy logging or severe cyclones, have long-lasting impacts on fruit production, while selective logging or moderate cyclonic windthrow cause more transient impacts. V. variegata is adapted to deal with an intrinsically erratic food supply by virtue of its reproductive biology and social behavior.

Animals↗

PubMed2005

Comparisons of food availability and group density of Japanese macaques in primary, naturally regenerated, and plantation forests.

We compared food availability and group density of Japanese macaques in Yakushima, southern Japan, among primary forest and two habitats that had been disturbed by logging and had different regeneration histories. The study was conducted in an undisturbed national park, forest that was logged 7-18 years ago and later naturally regenerated, and forest that was logged 19-27 years ago and later planted with Japanese cedar (Cryptomeria japonica) trees. The plantation forest was primarily composed of large Cryptomeria japonica trees at low stand density, while the naturally regenerated forest was composed of many small trees. The total basal area and number of trees in the primary forest were comparable to those in the plantation forest. Annual fruit production was greatest in the naturally regenerated forest, intermediate in the primary forest, and negligible in the plantation forest. Herb availability was high in the naturally regenerated forest, but low in the primary and plantation forests. The group density of Japanese macaques was high in the naturally regenerated forest, intermediate in the primary forest, and low in the plantation forest. Since group size in the naturally regenerated forest was small, individual density was almost the same as in the primary forest. These results suggest that the effects of regeneration on macaques vary between the two habitats. The plantation forest consisted mostly of Cryptomeria japonica, which supplies only flowers as food in a limited season, and had a lower density of macaques. On the other hand, in the naturally regenerated forest, fruit production and herb availability were high (probably because of the enhanced light conditions after logging), and the density of macaques was as high as in the primary forest.

Animals↗

PubMed2003

Simple method for the determination of rosiglitazone in human plasma using a commercially available internal standard.

To the best of our knowledge, bioanalytical methods to determine rosiglitazone in human plasma reported in literature use internal standards that are not commercially available. Our purpose was to develop a simple method for the determination of rosiglitazone in plasma employing a commercially available internal standard (IS). After the addition of celecoxib (IS), plasma (0.25 mL) samples were extracted into ethyl acetate. The residue after evaporation of the organic layer was dissolved in 750 microL of mobile phase and 50 microL was injected on to HPLC. The separation was achieved using a Hichrom KR 100, 250 x 4.6 mm C(18) with a mobile phase composition potassium dihydrogen phosphate buffer (0.01 m, pH 6.5):acetonitrile:methanol (40:50:10, v/v/v). The flow-rate of the mobile phase was set at 1 mL/min. The column eluate was monitored by fluorescence detector set at an excitation wavelength of 247 nm and emission wavelength of 367 nm. Linear relationships (r(2) > 0.99) were observed between the peak area ratio rosiglitazone to IS vs rosiglitazone concentrations across the concentration range 5-1000 ng/mL. The intra-run precision (%RSD) and accuracy (%Dev) in the measurement of rosiglitazone were <+/-10.69 and <-12.35%, respectively across the QC levels (50-1000 ng/mL). The extraction efficiency was >80% for both rosiglitazone and IS from human plasma. The lower limit of quantitation of the assay was 5 ng/mL. In summary, the methodology for rosiglitazone measurement in plasma was simple, sensitive and employed a commercially available IS.

Chromatography, High Pressure Liquid↗

PubMed2006

Single and three-color flow cytometry assay for intracellular zinc ion availability in human lymphocytes with Zinpyr-1 and double immunofluorescence: relationship with metallothioneins.

BACKGROUND: : The amount of available intracellular zinc is pivotal to regulate many cellular processes, including oxidative stress response and apoptotic mechanisms. Therefore it is not surprising that zinc homeostasis and dyshomeostasis is involved in many physiological and pathological states, respectively. Cell permeable zinc probes allow intracellular applications with microscopy technology, but flow cytometry (FC) applications have been scarcely explored, albeit they can be suited to study zinc homeostasis in different cell types, including rare cells. METHODS: : We describe a FC method able to estimate intracellular zinc ion availability and the intracellular capability to activate a zinc signal after treatment with an NO-donor (AcOM-DEA/NO) in human PBMCs, using the fluorescent zinc-specific probe, Zinpyr-1 (ZP1), alone or in association with CD4-PE and CD8-Cychrome mAb. RESULTS: : This method was able to detect an increase/decrease of intracellular zinc available in human fresh cultured PBMC and in immune subsets using AcOM-DEA/NO or TPEN, respectively. ZP1 mean fluorescence on gated histograms was sensitive to the amount of zinc added in the culture medium and significantly correlated to metallothioneins and total intracellular zinc. CONCLUSIONS: : FC applications using ZP1 may be a fast and useful tool to study zinc homeostasis in immune cells.

Adult↗

PubMed1976

[Studies on lysine availability with Tetrahymena pyriformis as the test organism].

A series of experiments was performed to verify the suitability of the protozoon Tetrahymena pyriformis (T.P.) for determining the lysine availability of feeds. The multiplication rate was estimated with the aid of organism counting, turbidimetry and reduction of triphenyltetrazolium chloride. The volume of T.P. was calculated on the basis of length and breadth measurements, Within higher rates of multiplication, there was connected a tendency towards larger organism volumes. A comparison of the growth tests showed that only turbidimetry is able to reflect, under certain conditions, the efficiency of the test organism in protein synthesis. The values for lysine availability varied widely according to the kind and pretreatment of the feedstuff, but did in no case attain those obtained with animal experiments. T.P. is, therefore, scarcely suited as a test organism for determining the protein quality and amino-acid availability of feedstuffs.

Animal Feed↗

PubMedDate not supplied

Progesterone receptor availability in mouse spermatozoa during epididymal transit and capacitation: ligand blot detection of progesterone-binding protein.

The goals of the present study were to determine the availability of progesterone (P4) receptor (P4r) in mouse sperm during maturation and capacitation and to make the first steps toward a characterization of P4r. It has been proposed that P4 is able to induce an acrosomal reaction (AR) by using a membrane P4r. This induction was verified in sperm isolated from the cauda epididymis (fully mature) when incubated in specific conditions that capacitate sperm. First, we set up the conditions in our laboratory to induce an AR in mature and capacitated sperm triggered by P4 that was detected by a chlortetracycline (CTC) assay. Then, we examined sperm isolated from the caput epididymis (immature) incubated under conditions that support cauda sperm capacitation and found that the AR could not be detected. Moreover, P4 was unable to induce the AR when it was applied to sperm isolated from either region and incubated under conditions that did not support capacitation. These results can be explained by changes in P4r availability. A suitable marker for P4r is the gold (Au)-P4 complex. This marker shows a binding capacity that can be visualized directly by electron microscopy (EM) and indirectly by silver-enhanced methods with light microscopy. The Au-P4 complex was localized in capacitated cauda sperm at the dorsal edge of the head. Using these techniques, we observed a significant decrease in both noncapacitated cauda sperm and caput sperm (whether incubated in capacitating media or not). Genomic P4r could be responsible for the signal detected, but antibodies against the P4 nuclear receptor did not recognize any sites in the sperm by immunostaining methodology. Instead, a 44-kd protein band was detected in the sperm by a ligand blot assay. In conclusion, P4 promotes the AR in capacitated cauda sperm but is unable to do so in noncapacitated or immature sperm because the availability of P4r increases during epididymal transit and after capacitation. The P4r responsible for this behavior is different from a classical nuclear receptor-on the basis of the immunostaining results-and is probably a protein close to 44 kd-on the basis of the ligand assay results.

Acrosome Reaction↗

PubMed1975

Growth limitation of 3T3 mouse fibroblasts by available growth surface area and medium components.

Studies with untransformed fibroblasts demonstrate that growth of these cells in culture can be limited by the availability of both growth surface and medium components. Experiments using cells grown on coverslips, in which the only variable was available growth surface, indicate that when the medium to cell ratio is high, surface area is the principal factor limiting growth. At low medium to cell ratios, however, growth of cells is predominantly limited by medium components. The final number of cells per culture is almost directly proportional to available surface area when the culture medium is changed daily.

Cell Count↗

PubMed2003

Performance of two commercially available sequence-based HIV-1 genotyping systems for the detection of drug resistance against HIV type 1 group M subtypes.

The use of genotyping assays for the detection and evaluation of drug resistance mutations within the polymerase gene of human immunodeficiency virus type 1 (HIV-1) is becoming increasingly relevant in the clinical management of HIV-1 infection. However, genotypic resistance assays available currently have been optimised for genetic subtype B strains of the virus and many clinical centres are presented with strains from subtypes A, C, and D. In the present report, we compare the performance of two sequence-based commercially available kits, the ViroSeq Genotyping System (Applied Biosystems, Foster City, CA) and the TruGene HIV-1 Genotyping Kit (Visible Genetics, Toronto, Ontario) against a panel of 35 virus isolates from HIV-1 Group M (subtypes A-J). Full-length consensus sequences were generated by the ViroSeq genotyping system for 26 of 31 (83.8%) of the isolates tested, in contrast to the TruGene genotyping system, which generated 16 of 30 (53%) usable sequences overall. Overall, subtype B isolates were sequenced with a greater degree of success than non-subtype B isolates. Discrepancies were found between the consensus sequences reported by each system for each sample (mean difference 1.0%; range 0.0-3.2%), but these appeared to be random and did not affect interpretation of the major resistance codons. In addition, both systems were able to amplify template RNA from low copy viral load plasma samples (10(2)-10(3) RNA copies/ml) taken from a random selection of patient samples encompassing subtypes A-C. While the availability of these genotyping systems should facilitate studies of HIV-1 drug resistance in countries in which these subtypes are prevalent, the performance against subtypes other than B needs to be improved.

Consensus Sequence↗

PubMed1988

Test of the nursing minimum data set: availability of data and reliability.

An initial study of the availability of the elements in the Nursing Minimum Data Set (NMDS) and intercoder reliability across four types of clinical settings is reported. These clinical settings included an acute care hospital, a nursing home, a home health care agency, and two ambulatory care clinics. The health records of 116 randomly selected subjects were reviewed to determine the availability of the NMDS elements. A randomly selected subset of 23 of these records provided data on intercoder agreement. All but four of the NMDS elements were available for 85% or more of the subjects. The average intercoder agreement across all NMDS elements was a satisfactory 91%. However, the intercoder agreement on some NMDS elements was much lower, suggesting a need to refine the definitions and procedures for collecting some of the NMDS elements. Where appropriate, coefficient Kappa and Pearson product moment correlation statistics for reliability are reported on individual NMDS elements.

Demography↗

PubMed1995

Reversal theory constructs and cigarette availability predict lapse early in smoking cessation.

The purpose of this study was to investigate the contribution of reversal theory constructs (i.e., metamotivational states) to understanding the outcome of tempting situations that occur in the first 6 weeks of smoking cessation. Cessation program participants (n = 68) were interviewed about tempting situations in which they either smoked or maintained abstinence. Both independent groups and repeated measures analyses indicated that metamotivational state (serious and goal-directed vs. playful and spontaneous) and cigarette availability significantly predicted outcome. Reversal theory constructs correctly predicted outcome of the tempting episode for 70% of the subjects, while cigarette availability was an accurate predictor for 74%. Metamotivational state and cigarette availability together predicted the outcome for 89% of the subjects.

Adult↗

PubMedDate not supplied

Development and applications of a city-level alcohol availability and alcohol problems database.

Data on alcohol availability and problems in all cities in Los Angeles County were collected from several different sources and linked together to form a Local Alcohol Availability Database (LAAD). The two major purposes of the project are to provide a city-level alcohol availability and alcohol-related problems database needed by local community alcohol policy planners and to collect the data necessary for research on the relationship between these measures. The prevalence of drunk driving arrests is displayed on a map. We describe how the LAAD has been used to guide alcohol policy decisions. A fixed year and city effects regression model suggests that outlet density is positively related to several alcohol-related problems.

Accidents, Traffic↗

PubMed2001

Sex differences in [123I]beta-CIT SPECT measures of dopamine and serotonin transporter availability in healthy smokers and nonsmokers.

Nicotine and other constituents of tobacco smoke elevate dopamine (DA) and serotonin (5-HT) levels in brain and may cause homeostatic adaptations in DA and 5-HT transporters. Since sex steroids alter DA and 5-HT transporter expression, the effects of smoking on DA and 5-HT transporter availability may differ between sexes. In the present study, DA and 5-HT transporter availabilities were quantitated using single photon emission computed tomography (SPECT) imaging approximately 22 h after bolus administration of [123I]beta-CIT, an analog of cocaine which labels DA and 5-HT transporters. Forty-two subjects including 21 pairs of age-, race-, and gender-matched healthy smokers and nonsmokers (12 female and 9 male pairs) were imaged. Regional uptake was assessed by the outcome measures, V3", which is the ratio of specific (i.e., ROI-cerebellar activity) to nondisplaceable (cerebellar) activity, and V3, the ratio of specific to free plasma parent. Overall, striatal and diencephalic [123I]beta-CIT uptake was not altered by smoking, whereas brainstem [123I]beta-CIT uptake was modestly higher (10%) in smokers vs. nonsmokers. When subgrouped by sex, regardless of smoking status, [123I]beta-CIT uptake was higher in the striatum (10%), diencephalon (15%), and brainstem (15%) in females vs. males. The sex*smoking interaction was not significant in the striatum, diencephalon, or brainstem, despite the observation of 20% higher brainstem [123I]beta-CIT uptake in male smokers vs. nonsmokers and less than a 5% difference between female smokers and nonsmokers. The results demonstrate higher DA and 5-HT transporter availability in females vs. males and no overall effect of smoking with the exception of a modest elevation in brainstem 5-HT transporters in male smokers. Although these findings are preliminary and need validation with a more selective 5-HT transporter radiotracer, the results suggest that brainstem 5-HT transporters may be regulated by smoking in a sex-specific manner.

Adult↗

PubMed2005

PET imaging of striatal dopamine D2 receptors in nonhuman primates: increases in availability produced by chronic raclopride treatment.

Previous research using positron emission tomography (PET) in monkeys has shown that attaining social dominance can result in increased DA D2 receptor availability and attenuated sensitivity to the reinforcing effects of cocaine. The present study utilized a within-subjects design to determine whether chronic treatment with the D2 receptor antagonist raclopride could similarly increase D2 receptor availability. Using the D2-selective radioligand [(18)F]fluoroclebopride (FCP), three adult male cynomolgus monkeys were scanned before and after chronic treatment with raclopride (0.01 mg/kg per h for 30 +/- 1 day) administered by a subcutaneous osmotic pump. Food-reinforced operant behavior was assessed during treatment. A transitory decrease in responding was observed during the initial eight days of raclopride treatment. Tolerance developed by the tenth session, and responding remained at baseline levels for the duration of treatment and after treatment was discontinued. Averaged across monkeys, chronic raclopride administration increased FCP distribution volume ratios (DVRs) between 12 and 20% in the caudate nucleus, putamen, and anterior cingulate cortex. When monkeys were re-scanned 9-12 months after termination of raclopride treatment, FCP DVRs remained elevated in two subjects, and decreased below baseline levels in the third monkey. Considering the reported 2% test/retest variability for FCP, these findings indicate that chronic treatment with a D2 receptor antagonist can produce large increases in D2 receptor availability as measured with PET. Individual differences in rates of recovery were observed, such that the increases in DVR persisted in two of three subjects.

Animals↗

PubMed1993

Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers.

Decreased dopaminergic function has been postulated to underlie cocaine addiction. To examine the possibility that dysfunction of brain regions subserved by the dopamine system could promote cocaine self-administration, positron emission tomography and a dual-tracer approach was used to examine dopamine D2 receptor availability and regional brain glucose metabolism in cocaine abusers. When compared to normal controls, cocaine abusers showed significant decreases in dopamine D2 receptor availability which persisted 3-4 months after detoxification. Decreases in dopamine D2 receptor availability were associated with decreased metabolism in several regions of the frontal lobes, most markedly orbito-frontal cortex and cingulate gyri. Dopamine dysregulation of these brain areas which are involved in the channeling of drive and affect could lead to loss of control resulting in compulsive drug-taking behavior.

Adult↗