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At least 1,225 records · Page 68Linked to original sources
PubMed1999

Calcium influx through L-type channels is required for selective activation of extracellular signal-regulated kinase by gonadotropin-releasing hormone.

The hypothalamic decapeptide gonadotropin-releasing hormone stimulates mobilization of two discrete pools of calcium in clonal (alphaT3-1) and primary pituitary gonadotropes. A multidisciplinary approach was implemented to investigate the effects of discrete calcium fluctuations on the signaling pathways linking the gonadotropin-releasing hormone receptor to activation of mitogen-activated protein kinases and immediate early genes. Blockade of calcium influx through nifedipine-sensitive voltage-gated calcium channels reduced buserelin-induced activation of extracellular signal-regulated kinase (ERK) and c-Fos while activation of c-Jun N-terminal kinase and c-Jun was unaffected. Inhibition of buserelin-stimulated ERK activity by nifedipine was also observed in rat pituitary cells in primary culture. Direct activation of alphaT3-1 cell L-type calcium channels with the agonist Bay-K 8644 resulted in phosphorylation of ERK and induction of c-Fos. However, simple voltage-induced channel activation did not produce a sufficient calcium signal, since depolarization with 35 mM KCl failed to induce activation of ERK. Depletion of intracellular calcium stores with thapsigargin did not affect buserelin-induced ERK activation. An inhibitor of protein kinase C decreased calcium influx through nifedipine-sensitive calcium channels and phosphorylation of ERK induced by buserelin. Pharmacological inhibition of protein kinase C did not block Bay-K 8644-induced ERK activation. These observations suggest that calcium influx through L-type channels is required for GnRH-induced activation of ERK and c-Fos and that the influence of calcium lies downstream of protein kinase C.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2003

Roost selection by Formosan leaf-nosed bats (Hipposideros armiger terasensis).

Patterns of roost use by Formosan leaf-nosed bats (Hipposideros armiger terasensis) were studied from November 1998 to April 2000. Structural characteristics, microclimates, and disturbance levels of 17 roosts used by H. a. terasensis and 15 roosts either used by other bat species (2) or not occupied by any bat species were compared. Roosts used by these bats were significantly larger in size and had greater areas covered by water compared to unused roosts. Entrances of active roosts were more likely to be east-west oriented. Hibernacula had lower entrances and ceilings than did roosts used only in summer. Higher temperatures were recorded in non-breeding roosts than in breeding roosts, but temperature gradients in these two types of roosts did not differ. In winter, hibernacula were warmer, and the temperature fluctuated less than in non-hibernacula. The relative humidities in summer roosts and hibernacula were nearly 100%. Disturbance levels were significantly higher in non-breeding roosts than in breeding roosts, and in non-hibernacula than in hibernacula. These results suggest that the Formosan leaf-nosed bats are selective of their roosts, but the pattern of their roost selection differs from those reported for bats of temperate regions. The reasons for such differences may be related to differences in body size, behavior, and reproductive strategy of the Formosan leaf-nosed bats living in a subtropical climate in Taiwan.

Animals↗
PubMed1984

Voltage-dependent kinetics of an anionic channel of large unit conductance in macrophages and myotube membranes.

Using the patch-clamp technique single-channel parameters and kinetic properties of an anionic channel are studied in cell-attached and excised membrane patches from peritoneal macrophages of mouse and cultured chicken myotubes. The channel has a unit conductance of about 340 pS with a Q10 of 1.3. In addition a subconductance state of about 210 pS is frequently adopted. The selectivity ratio of PCl/PNa is about 5. In excised membrane patches the activation of the channel appears to be independent of Ca either in the cytoplasmic or the extracellular medium. The channel induced current fluctuations appear in a burst like pattern. At least three non-conducting channel states could be distinguished kinetically. The mean lifetime of one of these states exhibits a strikingly steep voltage dependence which could be correlated to the mean shut interval between consecutive bursts. A similar steep voltage dependence was found for the mean lifetimes of bursts. The burst kinetic shows an about bell-shaped dependence on voltage. The results suggest that the burst kinetic and the kinetic within bursts are regulated by independent voltage sensitive mechanisms. The burst kinetic was analyzed by ensemble averages of voltage-jump current relaxations performed on the single channel level. A model of two voltage-sensitive gates is proposed for a description of the burst kinetic.

Animals↗
PubMed1986

Mitotic segregation of mitochondrial DNAs in human cell hybrids and expression of chloramphenicol resistance.

The relationship between the chloramphenicol (CAP)-resistant phenotype and the mtDNA genotype was investigated in segregating human, HeLa X HT1080, somatic cell hybrids. The parental mtDNAs were quantitated in heteroplasmic cells by using restriction fragment length polymorphisms (RFLPs) detected in Southern blots. CAP-resistant (R) X CAP-sensitive (S) hybrids selected and grown in CAP for brief periods had as little as 25% CAP-R mtDNA. With prolonged selection, the CAP-R mtDNA increased to 90-95%. Hybrids selected and passaged without CAP either retained both mtDNAs or progressively lost one mtDNA (mitotic segregation). The CAP-resistance phenotype of these hybrids changed abruptly when the proportion of CAP-R mtDNAs fluctuated around approximately 10% (threshold effect). Hybrids with greater than 25% HT1080 mtDNA had an additional characteristic. They cloned better with CAP than without. The cloning efficiency in CAP of hybrids having 90% HT1080 mtDNA was more than fivefold greater than the control.

Cell Fusion↗
PubMed2002

Recovery of electromyograph median frequency after lumbar muscle fatigue analysed using an exponential time dependence model.

The recovery of the median frequency of the power spectrum of the electromyogram (EMG) after fatigue has been studied to obtain reference data for healthy subjects (n = 55). In a seated position, the subjects performed a 45 s isometric back muscle contraction at 80% of maximal voluntary contraction, followed by 5 s contractions after 1, 2, 3, and 5 min in the recovery phase. In an additional reliability study (n = 11), this was performed six times. Surface EMG was recorded on four sites, namely, bilaterally from the lumbar muscles at the level of the first (L1) and fifth (L5) vertebrae. By non-linear regression, an exponential time dependence model was used to analyse the recovery of median frequency, giving recovery half-time as a resulting measure. Agreement with exponential time dependence was very good (coefficient of determination r(2) = 0.98) in the analysis of mean data (n = 55), with recovery half-times in the range 32-39 s on the four recording sites. Analysis of individual recordings, for which r(2) values in general were lower, revealed further details. Median values of the half-times in general agreed well with the half-times obtained from the analysis of mean data. Recovery half-time and median frequency slope during contraction were not correlated; this is in agreement with what may be expected from an exponential time dependence. Non-significant negative slopes occurred on apparently randomly selected sites, possibly indicating varying muscle coordination in the seated test method. The reliability of the half-time was not sufficient to allow for follow-up measurements on individuals, due to the fluctuations of the recovery data in recordings from individuals.

Adult↗
PubMed2005

Localization and correlation between NADPH-diaphorase and nitric oxide synthase isoforms in the porcine uterus during the estrous cycle.

Nitric oxide (NO), a highly reactive free radical is involved in vasodilation, neurotransmission, hormone secretion, and reproduction. Since all known nitric oxide synthase (NOS) isoforms possess NADPH-diaphorase (NADPH-d) activity, NADPH-d histochemistry was used as a commonly accepted procedure for NOS identification. The aim of our study was to determine the cellular localization of NADPH-d, eNOS, and iNOS in the porcine uterus and the correlation between NADPH-d and NOS activity in the early, middle, late luteal, and follicular phase of the estrous cycle. Light-microscopic observations of the sections revealed the differential expression of the NADPH-d in the analyzed stages of the estrous cycle. The most intense staining was observed in the luminal epithelium in the late luteal phase and in some groups of the endometrial glands in all studied stages. Positive reaction was also found in the endothelial cells of blood vessels and in the myometrium itself. Immunostaining for eNOS was observed in the luminal and glandular epithelium in all studied stages, but no clear fluctuations were observed. The endothelium of both endometrial and myometrial blood vessels displayed pronounced eNOS immunostaining. Strong iNOS staining was observed in the luminal epithelium in the late luteal and follicular phase and in selected groups of endometrial glands. Thus, only NADPH-d and iNOS undergo cyclic changes in the studied stages of the estrous cycle. The differential expression of NADPH-d/NOS in the porcine uterine horn during the estrous cycle suggests a role for NO in modulating uterine function.

Animals↗
PubMed1988

Isolation and partial characterization of an ion channel protein from human sperm membranes.

Human sperm cells were fractionated and plasma membrane proteins were separated by molecular gel sieving chromatography (Sephacryl S-200 followed by HPLC). A pore-forming protein was extracted from sperm cell membranes. The partially purified protein migrated with Mr 100,000-110,000, as determined by molecular sieving gel chromatography, and with a Mr 90,000 when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. The channel activity was also extracted with Triton X-114, suggesting a hydrophobic nature for this protein. This protein was incorporated into planar lipid bilayers, resulting in the formation of voltage-dependent ion channels. Single channel fluctuations of 130 pS/unit in 0.1 M NaCl were resolved; however, channels preferentially aggregated in triplets having an open state life-time that persisted for several seconds. The channels studied here were more selective for monovalent cations than anions, but also showed some permeability to anions and larger electrolytes, suggesting a large functional pore diameter. The role of this sperm channel in normal sperm physiology and/or fertilization is presently unclear.

Cell Membrane Permeability↗
PubMed1995

Food intake and the menstrual cycle: a retrospective analysis, with implications for appetite research.

The biological regulation of appetite is currently an important topic in nutrition, since hyperphagia has been implicated as the prime cause of obesity. Cyclical fluctuations in food intake occur in women across the menstrual cycle, with a periovulatory nadir and a peak in the luteal phase. These alterations in food intake, in response to ovarian steroid hormone changes may be more than 2.5 MJ/day, with the mean reported changes shown in 19 separate studies of 1.0 MJ/day. Hormonal induced fluctuations in food intake could, therefore, contribute to energy imbalance and consequent weight gain. Further, in nutrition studies involving women subjects where the menstrual cycle phase is not controlled, hormonally induced changes in food selection and intake may mask the often considerably smaller changes in response to experimental variables in appetite research.

Appetite↗
PubMed2003

Nonlinear dynamics indicates aging affects variability during gait.

OBJECTIVE: To investigate the nature of variability present in time series generated from gait parameters of two different age groups via a nonlinear analysis. DESIGN: Measures of nonlinear dynamics were used to compare kinematic parameters between elderly and young females. BACKGROUND: Aging may lead to changes in motor variability during walking, which may explain the large incidence of falls in the elderly. METHODS: Twenty females, 10 younger (20-37 yr) and 10 older (71-79 yr) walked on a treadmill for 30 consecutive gait cycles. Time series from selected kinematic parameters of the right lower extremity were analyzed using nonlinear dynamics. The largest Lyapunov exponent and the correlation dimension of all time series, and the largest Lyapunov exponent of the original time series surrogated were calculated. Standard deviations and coefficient of variations were also calculated for selected discrete points from each gait cycle. Independent t-tests were used for statistical comparisons. RESULTS: The Lyapunov exponents were found to be significantly different from their surrogate counterparts. This indicates that the fluctuations observed in the time series may reflect deterministic processes by the neuromuscular system. The elderly exhibited significantly larger Lyapunov exponents and correlation dimensions for all parameters evaluated indicating local instability. The linear measures indicated that the elderly demonstrated significantly higher variability. CONCLUSIONS: The nonlinear analysis revealed that fluctuations in the time series of certain gait parameters are not random but display a deterministic behavior. This behavior may degrade with physiologic aging resulting in local instability. RELEVANCE: Elderly show increased local instability or inability to compensate to the natural stride-to-stride variations present during locomotion. We hypothesized that this may be the one of the reasons for the increases in falling due to aging. Future efforts should attempt to evaluate this hypothesis by making comparisons to pathological subjects (i.e. elderly fallers), and examine the sensitivity and specificity of the nonlinear methods used in this study to aid clinical assessment.

Adult↗
PubMed1999

Tolcapone: a novel approach to Parkinson's disease.

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of tolcapone are reviewed. Tolcapone is the first drug brought to market from the new class of selective and reversible inhibitors of catechol-O-methyltransferase. Tolcapone is indicated for use in the treatment of Parkinson's disease as an adjunct to levodopa-carbidopa therapy in patients who are experiencing fluctuations in symptoms and who are not responding to or are not appropriate candidates for other adjunctive therapies. The absolute bioavailability of tolcapone after an oral dose is about 65%. Clinical trials have demonstrated that tolcapone 50-200 mg three times daily reduces "off" time in patients refractory to levodopa-carbidopa, Unified Parkinson's Disease Rating Scale scores, and the dosage of levodopa-carbidopa required for symptom suppression. The most frequent adverse effects of tolcapone are dyskinesia, nausea, sleep disorders, dystonia, orthostatic hypotension, diarrhea, dizziness, and hallucinations; also, there is a potential for elevation of liver transaminase concentrations in the blood. To date, three deaths from fulminant hepatic failure in association with tolcapone have been reported. Extensive liver function testing is required of all patients before and during therapy. The recommended starting dosage is 100 mg orally three times daily as an adjunct to levodopacarbidopa therapy; a concurrent reduction in the levodopa dosage of about 30% is suggested. Patient response should be monitored carefully during the first three weeks of therapy; treatment should be discontinued in patients failing to respond during this initial use. Tolcapone is of benefit in fluctuating Parkinson's disease, but benefits must be carefully weighed against risks in individual patients.

Antiparkinson Agents↗
PubMed1979

Respiratory oscillations and heat evolution in synchronous cultures of Candida utilis.

Synchronous cultures of the budding yeast Candida utilis prepared by continuous-flow size selection showed respiratory oscillations when the energy source was either glucose, acetate or glycerol. The period of the oscillations was about one-third of the cell cycle time (i.e. about 0.5 h). No fluctuations in heat evolution could be detected. In organisms growing with acetate or glycerol, the effects of cyanide, N,N'-dicyclohexylcarbodi-imide and carbonyl cyanide m-chlorophenylhydrazone (maximum inhibition of respiration at respiratory maxima, maximum uncoupling of energy conservation at respiratory minima) suggest that the control mechanism responsible for the oscillations is mitochondrial respiratory control in vivo. The effects of cyanide and N,N'-dicyclohexylcarbodi-imide on the respiration of cultures growing synchronously with glucose were different from those for cultures growing with the non-fermentable substrates; this suggests that the mitochondrial respiratory system interacts with the early reactions of glucose utilization.

Acetates↗
PubMed2003

Current noise in ac-driven nanoscale conductors.

The theory for current fluctuations in ac-driven transport through nanoscale systems is put forward. By use of a generalized, non-Hermitian Floquet theory we derive novel explicit expressions for the time-averaged current and the zero-frequency component of the power spectrum of current fluctuations. A distinct suppression of both the zero-frequency noise and the dc current occurs for suitably tailored ac fields. The relative level of transport noise, being characterized by a Fano factor, can selectively be manipulated by ac sources; in particular, it exhibits both characteristic maxima and minima near current suppression.

Journal Article↗
PubMed2003

Dynamics of majority rule in two-state interacting spin systems.

We introduce a two-state opinion dynamics model where agents evolve by majority rule. In each update, a group of agents is specified whose members then all adopt the local majority state. In the mean-field limit, where a group consists of randomly selected agents, consensus is reached in a time that scales ln(N, where N is the number of agents. On finite-dimensional lattices, where a group is a contiguous cluster, the consensus time fluctuates strongly between realizations and grows as a dimension-dependent power of N. The upper critical dimension appears to be larger than 4. The final opinion always equals that of the initial majority except in one dimension.

Journal Article↗
PubMed1999

GABA-Induced Cl- current in cultured embryonic human dorsal root ganglion neurons.

gamma-Aminobutyric acid (GABA)-activated channels in embryonic (5-8 wk old) human dorsal root ganglion (DRG) neurons in dissociated culture were characterized by whole cell and single-channel techniques. All DRG neurons when held at negative holding membrane potentials displayed inward current to micromolar concentrations of GABA applied by pressure pulses from closely positioned micropipettes. The current was directly proportional to the concentration of GABA (EC50, 111 microM; Hill coefficient, 1.7). DRG neurons also responded to micromolar concentrations of pentobarbital and alphaxalone but not to cis-4-aminocrotonic acid (CACA), glycine, or taurine. Baclofen (100 microM) affected neither the holding currents nor K+ conductance (when patch pipettes were filled with 130 mM KCl) caused by depolarizing pulses. Whole cell GABA-currents were blocked by bicuculline, picrotoxin, and t-butylbicyclophosphorothionate (TBPS; all at 100 microM). The reversal potential of whole cell GABA-currents was close to the theoretical Cl- equilibrium potential, shifting with changes in intracellular Cl- concentration in a manner expected for Cl--selective channels. The whole cell I-V curve for GABA-induced currents demonstrated slight outward rectification with nearly symmetrical outside and inside Cl- concentrations. Spectral analysis of GABA-induced membrane current fluctuations showed that the kinetic components were best fitted by a triple Lorentzian function. The apparent elementary conductance for GABA-activated Cl- channels determined from the power spectra was 22.6 pS. Single-channel recordings from cell-attached patches with pipettes containing 10 microM GABA indicated that GABA-activated channels have a main and a subconductance level with values of 30 and 19 pS, respectively. Mean open and closed times of the channel were characterized by two or three exponential decay functions, suggesting two or three open channel states and two closed states. Single channels showed a lack of rectification. The actions of GABA on cultured human embryonic DRG neurons are mediated through the activation of GABAA receptors with properties corresponding to those found in the CNS of human and other mammalian species but differing from those of cultured human adult DRG neurons.

Adult↗
PubMed2002

Radiation research society 1952-2002. Physics as an element of radiation research.

Since its inception in 1954, Radiation Research has published an estimated total of about 8700 scientific articles up to August 2001, about 520, or roughly 6%, of which are primarily related to physics. This average of about 11 articles per year indicates steadily continuing contributions by physicists, though there are appreciable fluctuations from year to year. These works of physicists concern radiation sources, dosimetry, instrumentation for measurements of radiation effects, fundamentals of radiation physics, mechanisms of radiation actions, and applications. In this review, we have selected some notable accomplishments for discussion and present an outlook for the future.

History, 20th Century↗
PubMed1990

[Extracardiac risk factors in heart surgery--drugs].

Preoperative long-term medication continued during and after cardiac surgery may cause dangerous situations, including risks due to drug interactions, and risks as a result of contraindications to previously beneficial substances that develop during the surgical procedure. In the case of a lege-artis-performed anesthesia there is no urgent reason to postpone cardiac surgery because of previous drug treatment. Nevertheless, some compounds or groups of therapeutic agents can cause undue risk. These drugs are: acetylsalicylic acid (known to increase the bleeding tendency), and cardiac glycosides (which produces intraoperative dysrhythmias). Tricyclic antidepressants considerably intensify the effects of sympathomimetic agents. Monoamine-oxidase inhibitors, especially when combined with indirectly acting sympathomimetic agents or pethidine, may cause fluctuations of blood pressure that are difficult to control or can even precipitate a hypertensive crisis. In these cases preoperative discontinuation of drugs needs to be considered. The time of discontinuation must be chosen selectively for each active substance. The most important point for prevention of drug-related risk is to take a precise medical history, including previous drug treatment, in order to take future intraoperative precautions.

Contraindications↗
PubMed1988

Tumorigenic transformation of rat FR3T3 fibroblasts carrying an activated myc oncogene requires subsequent mutational events.

Early passage FR3T3 rat cells were co-transfected with a neo resistance gene and pSVc-myc-1, an SV40-driven expression vector carrying an activated murine myc oncogene. Selection in G418 medium produced clones expressing the exogenous myc gene at various levels, with a concomitant loss of expression of the normal c-myc allele. These clones were phenotypically normal, but, in fluctuation tests performed according to Luria and Delbrück (1943) on subcultures independently derived from the same clone, transformed foci appeared as stochastic events with a wide range of fluctuation. These results indicate that expression of the oncogene was not sufficient to induce the appearance of transformed growth properties, and that secondary genetic changes are required, most likely mutations in cellular proto-oncogenes. Within a single clone, independent transformants exhibited different tumorigenic potentials, spanning from high efficiency to no detectable tumor induction, without any clear correlation with their degree of in vitro transformation. Tumors and cell lines established from independent tumors, while maintaining the exogenous myc gene without gross rearrangement of its structure, no longer expressed the oncogene and resumed the expression of the normal allele.

Animals↗
PubMed1997

Anchoring and scaffold proteins for kinases and phosphatases.

Many hormones mediate their intracellular actions by triggering signal transduction pathways that alter the phosphorylation state of key regulatory proteins. Protein phosphorylation is a reversible process involving two classes of signaling enzymes: protein kinases, which catalyze the transfer of phosphate from ATP onto substrate proteins, and phosphoprotein phosphatases, which perform the dephosphorylation step. To insure tight control of hormonally initiated phosphorylation events, the activity of multifunctional kinases and phosphatases is precisely regulated and responds to fluctuations in diffusible second messengers such as Ca2+, phospholipid, and cAMP. Another mechanism that contributes to their regulation is to restrict the location of these enzymes to certain subcellular compartments. Subcellular targeting enhances the selectivity of serine/threonine phosphatases and kinases by favoring their accessibility to certain substrate proteins. Compartmentalization is achieved through a "targeting moiety," which is defined as that part of a phosphatase or kinase that directs the catalytic subunit to a certain subcellular environment. The targeting moiety restricts the location of a phosphatase or kinase through association with a "targeting locus." These are often structural membrane proteins, cytoskeletal components, or cellular organelles. Targeting subunits for the type I phosphatase and protein kinase C have been identified; however, the focus of this chapter centers around a family of anchoring proteins, called AKAPs, that localize the type II cAMP-dependent protein kinase (PKA). Structure-function analysis suggest that each anchoring protein binds to the RII dimer through a conserved amphipathic helix region and is tethered to specific subcellular sites via association of a targeting domain with structural proteins or cellular organelles. Peptides patterned after the amphipathic region have been used to probe the functional significance of PKA anchoring inside cells and have begun to be established by that disruption RII/AKAP interaction in vivo has concomitant effects on certain PKA-mediated phosphorylation events. In addition, multivalent binding proteins such as AKAP79 and AKAP250 have been characterized and appear to serve as platforms for the assembly of kinase/phosphatase signaling complexes. Collectively, these studies suggest that the AKAPs represent a growing family of regulatory proteins that provide a molecular architecture that organizes the intracellular location of a single or multiple multifunctional kinase.

A Kinase Anchor Proteins↗