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Biomedical subjects

A Arnon

Publications and source records attributed to A Arnon.

At least 19 recordsLinked to original sources

Primary pterygium recurrence time.

BACKGROUND: The time to recurrence after surgical removal of primary pterygium (pterygium) and the association between the rate of recurrence and the postoperative interval remain unclear. OBJECTIVES: To determine the amount of follow-up time needed to identify recurrence in patients after surgical removal of pterygium. METHODS: We reviewed the files of 143 patients (143 eyes) with recurrent pterygium to determine the interval from surgery to recurrence. RESULTS: Almost all (91.6%) of the recurrences appeared by 360 days after surgery. CONCLUSIONS: One year is the optimal follow-up time to identify recurrence of pterygium.

Adult↗

Na(+) entry via store-operated channels modulates Ca(2+) signaling in arterial myocytes.

In many nonexcitable cells, hormones and neurotransmitters activate Na(+) influx and mobilize Ca(2+) from intracellular stores. The stores are replenished by Ca(2+) influx via "store-operated" Ca(2+) channels (SOC). The main routes of Na(+) entry in these cells are unresolved, and no role for Na(+) in signaling has been recognized. We demonstrate that the SOC are a major Na(+) entry route in arterial myocytes. Unloading of the Ca(2+) stores with cyclopiazonic acid (a sarcoplasmic reticulum Ca(2+) pump inhibitor) and caffeine induces a large external Na(+)-dependent rise in the cytosolic Na(+) concentration. One component of this rise in cytosolic Na(+) concentration is likely due to Na(+)/Ca(2+) exchange; it depends on elevation of cytosolic Ca(2+) and is insensitive to 10 mM Mg(2+) and 10 microM La(3+). Another component is inhibited by Mg(2+) and La(3+), blockers of SOC; this component persists in cells preloaded with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid to buffer Ca(2+) transients and prevent Na(+)/Ca(2+) exchange-mediated Na(+) entry. This Na(+) entry apparently is mediated by SOC. The Na(+) entry influences Na(+) pump activity and Na(+)/Ca(2+) exchange and has unexpectedly large effects on cell-wide Ca(2+) signaling. The SOC pathway may be a general mechanism by which Na(+) participates in signaling in many types of cells.

Angiotensin II↗

Ouabain augments Ca(2+) transients in arterial smooth muscle without raising cytosolic Na(+).

Ouabain and other cardiotonic steroids (CTS) inhibit Na(+) pumps and are widely believed to exert their cardiovascular effects by raising the cytosolic Na(+) concentration ([Na(+)](cyt)) and Ca(2+). This view has not been rigorously reexamined despite evidence that low-dose CTS may act without elevating [Na(+)](cyt); also, it does not explain the presence of multiple, functionally distinct isoforms of the Na(+) pump in many cells. We investigated the effects of Na(+) pump inhibition on [Na(+)](cyt) (with Na(+) binding benzofuran isophthalate) and Ca(2+) transients (with fura 2) in primary cultured arterial myocytes. Low concentrations of ouabain (3-100 nM) or human ouabain-like compound or reduced extracellular K(+) augmented hormone-evoked mobilization of stored Ca(2+) but did not increase bulk [Na(+)](cyt). Augmentation depended directly on external Na(+), but not external Ca(2+), and was inhibited by 10 mM Mg(2+) or 10 microM La(3+). Evoked Ca(2+) transients in pressurized small resistance arteries were also augmented by nanomolar ouabain and inhibited by Mg(2+). These results suggest that Na(+) enters a tiny cytosolic space between the plasmalemma (PL) and the adjacent sarcoplasmic reticulum (SR) via an Mg(2+)- and La(3+)-blockable mechanism that is activated by SR store depletion. The Na(+) and Ca(2+) concentrations within this space may be controlled by clusters of high ouabain affinity (alpha3) Na(+) pumps and Na/Ca exchangers located in PL microdomains overlying the SR. Inhibition of the alpha3 pumps by low-dose ouabain should raise the local concentrations of Na(+) and Ca(2+) and augment hormone-evoked release of Ca(2+) from SR stores. Thus the clustering of small numbers of specific PL ion transporters adjacent to the SR can regulate global Ca(2+) signaling. This mechanism may affect vascular tone and blood flow and may also influence Ca(2+) signaling in many other types of cells.

Animals↗

Calmodulin regulation of light adaptation and store-operated dark current in Drosophila photoreceptors.

Phototransduction in Drosophila occurs through inositol lipid signaling that results in Ca2+ mobilization. In this system, we investigate the hitherto unknown physiological roles of calmodulin (CaM) in light adaptation and in regulation of the inward current that is brought about by depletion of cellular Ca2+ stores. To see the effects of a decreased Ca-CaM content in photoreceptor cells, we used several methods. Transgenic Drosophila P[ninaCDeltaB] flies, which have CaM-deficient photoreceptors, were studied. The peptide inhibitor M5, which binds to Ca-CaM and prevents its action, was applied. A Ca2+-free medium, which prevents Ca2+ influx and thereby diminishes the generation of Ca-CaM, was used. The decrease in the Ca-CaM level caused the following effects. (i) Fluorescence of Ca2+ indicator revealed an enhanced light-induced Ca2+ release from internal stores. (ii) Measurements of the light-induced current in P[ninaCDeltaB] cells showed a reduced light adaptation. (iii) Internal dialysis of M5 initially enhanced excitation and subsequently disrupted the light-induced current. (iv) An inward dark current appeared after depletion of the Ca2+ stores with ryanodine and caffeine. Importantly, application of Ca-CaM into the photoreceptor cells prevented all of the above effects. We propose that negative feedback of Ca-CaM on Ca2+ release from ryanodine-sensitive stores mediates light adaptation, is essential for light excitation, and keeps the store-operated inward current under a tight control.

Acclimatization↗

Calmodulin regulation of calcium stores in phototransduction of Drosophila.

Phototransduction in Drosophila occurs through the ubiquitous phosphoinositide-mediated signal transduction system. Major unresolved questions in this pathway are the identity and role of the internal calcium stores in light excitation and the mechanism underlying regulation of Ca2+ release from internal stores. Treatment of Drosophila photoreceptors with ryanodine and caffeine disrupted the current induced by light, whereas subsequent application of calcium-calmodulin (Ca-CaM) rescued the inactivated photoresponse. In calcium-deprived wild-type Drosophila and in calmodulin-deficient transgenic flies, the current induced by light was disrupted by a specific inhibitor of Ca-CaM. Furthermore, inhibition of Ca-CaM revealed light-induced release of calcium from intracellular stores. It appears that functional ryanodine-sensitive stores are essential for the photoresponse. Moreover, calcium release from these stores appears to be a component of Drosophila phototransduction, and Ca-CaM regulates this process.

Animals↗

Coexpression of Drosophila TRP and TRP-like proteins in Xenopus oocytes reconstitutes capacitative Ca2+ entry.

Capacitative Ca2+ entry is a component of the inositol-lipid signaling in which depletion of inositol 1,4,5-trisphosphate (InsP3)-sensitive Ca2+ stores activates Ca2+ influx by a mechanism that is still unknown. This pathway plays a central role in cellular signaling, which is mediated by many hormones, neurotransmitters, and growth factors. Studies of Drosophila photoreceptors provided the first putative capacitative Ca2+ entry mutant designated transient receptor potential (trp) and a Drosophila gene encoding TRP-like protein (trpl). It is not clear how the Ca2+ store depletion signal is relayed to the plasma membrane and whether both TRP and TRPL participate in this process. We report here that coexpressing Drosophila TRP and TRPL in Xenopus oocytes synergistically enhances the endogenous Ca(2+)-activated Cl- current and produces a divalent inward current. Both of these currents are activated by Ca2+ store depletion. In the absence of Ca2+, Mg2+ is the main charge carrier of the divalent current. This current is characterized by lanthanum sensitivity and a voltage-dependent blocking effect of Mg2+, which is relieved at both hyperpolarizing (inward rectification) and depolarizing (outward rectification) potentials. The store-operated divalent current is neither observed in native oocytes nor in oocytes expressing either TRP or TRPL alone. The production of this current implicates a cooperative action of TRP and TRPL in the depletion-activated current.

Animals↗

Synthetic recombinant vaccines against viral agents.

Synthetic recombinant vaccines are expression vectors incorporating defined epitope(s) of microbial agents. They are prepared by inserting synthetic oligonucleotide(s) coding for previously identified relevant epitopes into the genome of a desired vector, using recombinant DNA technology. The results discussed indicate that immunization with such vaccines carrying viral epitopes may lead to protective immunity against viral agents. Oligonucleotides coding for three influenza epitopes stimulating B cells, T helper cells and cytotoxic lymphocytes were individually inserted into the flagellin gene of a Salmonella vaccine strain. Immunization of mice with the resultant recombinant bacteria or their isolated flagella induced a specific mucosal anti-influenza protective response. The most efficient vaccine consisted of all three recombinant flagella, administered intranasally. The protection elicited was cross-strain specific, long-lasting and efficient against a lethal viral challenge.

Administration, Oral↗

The light response of Drosophila photoreceptors is accompanied by an increase in cellular calcium: effects of specific mutations.

Photoreceptors of dissociated Drosophila retinae were loaded with the fluorescent Ca2+ indicators, fluo-3 and Calcium Green-5N. In fluo-3-loaded, wild-type photoreceptors, a rapid increase in fluorescence (Ca2+ signal) accompanied the light-evoked inward current. Removal of extracellular Ca2+ greatly reduced the Ca2+ signal, indicating Ca2+ influx as its major cause. In Calcium Green-5N-loaded trp mutants, which lack a large fraction of the Ca2+ permeability underlying the light-evoked inward current, the Ca2+ signal was smaller relative to wild-type photoreceptors. Fluo-3-loaded norpA mutant photoreceptors, which lack a light-activated phospholipase C, generated no light-evoked inward current and no Ca2+ signal. The phosphoinositide pathway therefore appears necessary for both excitation and changes in cytosolic free Ca2+ concentration.

Aniline Compounds↗

Computer-generated physician and patient reminders. Tools to improve population adherence to selected preventive services.

Despite an emerging consensus on appropriate preventive services, a minority of patients receive them. A study was undertaken to assess the impact of computer-generated reminders to adult patients, their physicians, or both patients and physicians on adherence to five recommended preventive services: cholesterol measurements, fecal occult blood testing, mammography, Papanicolaou smears, and tetanus immunization. During the academic year 1988-1989, all 7397 adult patients and their 49 physicians in a university family medicine clinical practice were randomized by practice group into one of four study groups: control, physician reminders, patient reminders, and both physician and patient reminders. Adherence was defined in community-oriented terms: the percentage of patients within each group who had received the preventive service in the recommended interval. During the study period, adherence to four of the five preventive services increased significantly, with the largest increases in the physician and patient reminder group: cholesterol measurements increased from 19.5% to 38.1%, fecal occult blood testing 9.3% to 27.0%, mammography 11.4% to 27.1%, and tetanus immunization 23.4% to 35.4% (for each increase, P less than .0001, McNemar's chi-square test). In general, increases were greater in blacks and in patients with any form of insurance coverage. Computer-based physician and patient reminder systems have great promise of improving adherence to preventive services in primary care settings.

Adult↗

Compliance with five health promotion recommendations in a university-based family practice.

Although numerous recommendations are available to guide the primary care physician's provision of preventive health services, a minority of Americans receive recommended care. This study assessed the extent to which patients in a large, university-based family medicine program were receiving five well-accepted health promotion services. These services included fecal occult blood testing, Papanicolaou smears, mammography, serum cholesterol measurements, and tetanus immunization. Demographic factors associated with receipt of these services were assessed. A minority of active patients received the five health promotion services in the recommended interval: fecal occult blood testing 13%, Papanicolaou smear 41%, mammography 16%, cholesterol measurements 20%, and tetanus immunization 19%. The patient's physician practice group, type of medical insurance, physician visit frequency, and increasing age were associated with compliance with the five studied health promotion services.

Academic Medical Centers↗

Acetylcholine modulates two types of presynaptic potassium channels in vertebrate motor nerve terminals.

Using external microelectrodes to record local circuit currents from preterminal motor nerve axons, two distinct populations of potassium (K) channels were identified in frog motor nerve terminals: delayed rectifier and calcium-activated K channels. Both are sensitive to the transmitter acetylcholine (ACh) which, when externally applied, blocks them in concentrations in the millimolar range. As this action also is not prevented by nicotinic and muscarinic antagonists, it probably is not mediated by classical cholinergic receptors. This cholinergic sensitivity of presynaptic K channels may account for the hyperexcitability of motor nerve terminals manifested when ACh accumulates in the junctional cleft.

Acetylcholine↗

Two shortened versions of the Cornell Medical Index--a new test of their validity.

Two shortened versions of the Cornell Medical Index (CMI) were tested for concurrent validity using two reference groups. Sensitivity, specificity and relative liability were computed and found to be of relatively low value. The usefulness of the questionnaires for screening the emotionally disturbed was found to be affected by respondents' sociodemographic characteristics such as age and sex and, in particular, educational level and ethnicity.

Adult↗

Emotional disorders in six Israeli villages.

This is a report on a psychiatric epidemiological census conducted in six Israeli villages. The method of case identification relied on data extracted from medical cards and the use of two shortened versions of the CMI. The results showed a distribution affected by sex, age, ethnicity, education, and "status consumer". A comparison with other Israeli studies is made.

Adult↗