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Biomedical subjects

B A Weissman

Publications and source records attributed to B A Weissman.

At least 73 records · Page 4Linked to original sources

Maximal electroshock increases the density of [3H]Ro 5-4864 binding to mouse cerebral cortex.

The effects of chemically and electrically-induced convulsions on the binding of [3H]Ro 5-4864 to peripheral benzodiazepine receptors (PBR) was studied in both peripheral tissues and the central nervous system (CNS). Acute, maximal electroshock (MES) increased the density of PBR in mouse cerebral cortex as evidenced by a 30% increase in the Bmax of this archetypic ligand. These values returned to control levels by 60 minutes after MES treatment. In contrast, thirty and sixty minutes after convulsions induced by Ro 5-4864, strychnine, or pentylenetetrazol, neither the Bmax nor Kd of [3H]Ro 5-4864 binding to mouse cerebral cortical membranes was altered. The increase in [3H]Ro 5-4864 binding to cortex observed 30 minutes after MES was blocked by anticonvulsant doses of phenobarbital, phenytoin and clonazepam. No changes in the characteristics of [3H]Ro 5-4864 binding was observed in cerebellar or hippocampal membranes 30 minutes following acute MES. Further, after long-term MES administration (1 treatment/day, 5 days), no change in PBR density could be detected 30 minutes after the last MES. Finally, while no change in PBR density was noted in the kidneys 30 minutes after the MES, a significant increase in PBR density was seen in the cardiac ventricles. These results demonstrate a selective modulation of PBR density by MES, suggesting that the PBR could be involved in either the generation of seizures or in postictal compensatory processes.

Animals↗

Compliance in contact lens care.

Fifty patients who were originally fitted or refitted with daily-wear contact lenses at the UCLA contact lens service were interviewed on the nature of their care system compliance and hygiene. Good compliance was defined as meeting three preset, standardized criteria (hand washing before lens manipulation, correct use of a FDA-approved care system, and adherence to a daily-wear schedule). Twenty of our patients, or 40%, were found to be noncompliant. Noncompliance occurred more frequently in the 10 to 30 year age group and in those over 50 years of age and after lenses had been worn for more than 2 years. We also noted that patients with contact lens experience predating our contact lens care were more noncompliant as a group than those who only obtained contact lenses and care through our practice.

Adolescent↗

Bay K 8644-induced changes in the ECG pattern of the rat and their inhibition by antianginal drugs.

1. The effects of intracarotid administration of Bay K 8644 on the ECG pattern along with their reversal by antianginal drugs were investigated in anaesthetized rats. 2. Intracarotid injections of Bay K 8644 (0.5-50.0 micrograms kg-1) produced a dose-related transient increase in systemic blood pressure. 3. The pressor response was accompanied by ST segment elevation (0.5-10.0 micrograms kg-1), ST segment depression concomitant with the occurrence of arrhythmias (20.0 micrograms kg-1), or A-V block (50.0 micrograms kg-1). 4. ST segment elevation reached its maximal value within 15 s and could be observed for 30-240 s. 5. The increase in blood pressure was immediate (within 5 s) and short lasting (30-120 s). After the initial increase it returned to control levels (0.5-20.0 micrograms kg-1) or dropped below (50.0 micrograms kg-1). 6. The ST segment elevation caused by 5.0 micrograms kg-1 Bay K 8644 (submaximal dose) was blocked by antianginal drugs (e.g. nitroglycerin, nifedipine and diltiazem) and by the peripheral benzodiazepine receptor antagonist PK 11195. However, the pressor response was not blocked by any of the drugs used. 7. ST segment elevation (or depression) induced by intracarotid administration of Bay K 8644 provides a useful tool for the evaluation of potential antianginal drugs.

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

Enhancement of [3H]DAGO1 binding to rat brain by low concentrations of monovalent cations.

The effects of mono- and di-valent cations and the nonhydrolyzable guanyl nucleotide derivative 5'-guanylimidodiphosphate (Gpp(NH)p) on the binding of the selective, high affinity mu-opiate receptor agonist, [3H]DAGO ([3H]Tyr-D-Ala-Gly-Mephe-Gly-ol), to rat brain membranes were studied in a low ionic strength 5 mM Tris-HCl buffer. Na+ and Li+ (50 mM) maximally increased [3H]DAGO binding (EC50 values for Na+, 2.9 mM and Li+, 6.2 mM) by revealing a population of low affinity binding sites. The density of high affinity [3H]DAGO binding sites was unaffected by Na+ and Li+, but was maximally increased by 50 mM K+ and Rb+ (EC50 values for K+, 8.5 mM and Rb+, 12.9 mM). Divalent cations (Ca2+, Mg2+; 50 mM) inhibited [3H]DAGO binding. Gpp(NH)p decreased the affinity of [3H]DAGO binding, an effect that was enhanced by Na+ but not by K+. The binding of the mu-agonist [3H]dihydromorphine was unaffected by 50 mM Na+ in 5 mM Tris-HCl. In 50 mM Tris-HCl, Na+ (50 mM) inhibited [3H]DAGO binding by decreasing the density of high affinity binding sites and promoting low affinity binding. The effects of Na+ in 5 mM and 50 mM Tris-HCl were also investigated on the binding of other opiate receptor agonists and antagonists. [3H]D-Ala-D-Leu-enkephalin binding was increased and inhibited. [3H]etorphine binding increased and was unchanged, and both [3H]bremazocine and [3H]naloxone binding increased by 50 mM Na+ in 5 mM and 50 mM Tris-HCl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Keratitis and contact lens wear: a review.

The most feared complications of contact lens wear are keratitis and infectious corneal ulceration. This article first defines terms for the clinical practitioner, and then describes and illustrates clinical presentation and management.

Bacterial Infections↗

Results of the extended wear contact lens survey of the Contact Lens Section of the American Optometric Association.

Surveys of contact lens practice, comparing the use of daily wear and extended wear cosmetic soft contact lenses, were distributed to almost 3,000 members of the Contact Lens Section of the American Optometric Association. There were 759 responses received of which 440 were considered valid for analysis. The results of our analysis suggest that slightly more physiological complications are encountered with extended than with daily wear of contact lenses. Most optometrists (96%), however, are satisfied with this modality and continue prescribing extended wear lenses, although many have decreased the number of days over which patients are advised to use the lenses before removal and cleaning. Most of the respondees now favor medium water content, thin lens designs for extended wear use, with 70% of them suggesting weekly removal, cleaning and aseptization. Peroxide cleaning regimens are most popular for this function.

Contact Lenses, Extended-Wear↗

The use of spherical power effect bitoric rigid contact lenses in hospital practice.

In this retrospective study of astigmatic contact lens dispensing in the hospital setting, 680 patients were noted to have been dispensed new contact lens prescriptions over a specific 20-month period. Seventy-five patients (11%) received at least one astigmatic rigid or hydrogel contact lens. Forty-nine patients received at least one rigid astigmatic lens; 43 patients (63 eyes)--or about 87% of all rigid lens fittings--were dispensed spherical power effect (SPE) design rigid contact lenses. We find that we usually prescribe bitoric rigid lenses with the flatter (longer) meridian of the lens base curve about 0.50 diopters steeper than the flattest (longest) corneal meridian. Mean diameter was 9.3 mm, and about 80% of lenses were made from rigid gas permeable materials. The majority of patients were successful from a clinical perspective, with most attaining visual acuity equal to or better than with maximum spectacle correction, and with good comfort and physiological results.

Adolescent↗

Corneal ulcers associated with daily-wear and extended-wear contact lenses.

Over a 21-month period, we treated corneal ulcers in 11 patients using daily-wear contact lenses and 29 patients using extended-wear contact lenses. Since more patients use daily-wear than extended-wear lenses, this suggests that patients using extended-wear lenses are at greater risk for the development of corneal ulcers. Positive bacterial cultures were obtained from the corneal scrapings of nine of 11 patients using daily-wear lenses and 20 of 29 patients using extended-wear lenses. In the daily-wear group, all 11 patients failed to exercise satisfactory care in using and disinfecting their contact lenses: three did not wash their hands before manipulating the contact lenses, eight wore them overnight, two did not use any disinfecting system, and four had contaminated contact lens cases, solutions, or drops. In the extended-wear group, 17 patients failed to exercise satisfactory care in using and disinfecting their contact lenses: 12 had contaminated contact lens care systems, two did not use any disinfection system, five reported not washing their hands before contact lens manipulation, and two disinfected their contact lenses at intervals of more than a month. We were unable to identify any defect in the way 12 patients took care of their extended-wear lenses, suggesting that there may be a problem with these contact lenses even when care is satisfactory.

Adult↗

Dihydropyridine calcium channel antagonists binding in non-mammalian vertebrates: characterization and relationship to 'peripheral-type' binding sites for benzodiazepines.

The densities of dihydropyridine calcium antagonist binding sites were examined in brains and cardiac issues of representative species from 4 classes of non-mammalian vertebrates (aves, pigeon; amphibia, frog; reptilia, chameleon; and osteichthyes, trout) previously shown to have low or undetectable levels of 'peripheral-type' binding sites for benzodiazepines. Dihydropyridine binding sites were present in brain and cardiac tissue of these 4 classes of non-mammalian vertebrates. The apparent dissociation constants for [3H]nitrendipine in non-mammalian vertebrates were comparable to those found in mammalian (rat) tissues. The densities of [3H]nitrendipine binding sites in brain and cardiac tissues were highest in the pigeon, with lower densities in tissues from chameleon, frog and trout. The densities of dihydropyridine binding sites in the latter tissues were comparable to those observed in the rat. Thus, dihydropyridine binding sites are phylogenetically diverse yet have similar kinetic characteristics in mammals and non-mammalian vertebrates. Despite the pharmacologic evidence that links dihydropyridine binding sites and peripheral binding sites for benzodiazepines in mammals, the earlier evolutionary appearance of the former sites suggest that even though they may share one or more common effector mechanisms, they are discrete entities.

Animals↗

Acylating phencyclidines irreversibly enhance brain calcium antagonist binding.

Phencyclidine was previously shown to allosterically increase the apparent affinity of the dihydropyridine ( [3H]nitrendipine) calcium antagonist binding site in a lysed synaptosomal membrane preparation of rat forebrain. Treatment of a similar preparation of mouse forebrain with 4-isothiocyanato-1-(1-phenylcyclohexyl) piperidine (FOURPHIT), an acylating phencyclidine derivative, resulted in a concentration dependent (0.1-10 microM), irreversible, increase in the apparent affinity of [3H]nitrendipine in contrast to the effects of phencyclidine which were reversible. The FOURPHIT isomer, 1-[1-(3-isothiocyanatophenyl) cyclohexyl] piperidine (METAPHIT), (10 microM) also irreversibly increased the apparent affinity of [3H]nitrendipine, but was much less efficacious than FOURPHIT. Phencyclidine blocked the irreversible increase in the apparent affinity of [3H]nitrendipine produced by FOURPHIT. The interactions of multivalent cations and the calcium antagonist diltiazem with the [3H]nitrendipine binding site were altered following treatment of membranes with FOURPHIT. These studies suggest that FOURPHIT irreversibly interacts with the same sites as PCP, and thus may be a useful tool with which to further probe both the behavioral and biochemical interactions between phencyclidine and the dihydropyridine calcium antagonist binding site.

Animals↗

Probes for narcotic receptor mediated phenomena. 9. Synthesis of (+/-)-(3 alpha,6a alpha,11a beta)-1,3,4,5,6,11a-hexahydro-2-methyl-2H-3,6a- methanobenzofuro[2,3-c]azocin-10-ol, an oxide-bridged 5-(m-hydroxyphenyl)morphan.

The synthesis of racemic (3 alpha,6a alpha,11a beta)-1,3,4,5,6,11a- hexahydro-2-methyl-2H-3,6a-methanobenzofuro[2,3-c]azocin -10-ol (2d) is described. The route used acid-catalyzed ring closure of enamine 5 to yield the unsaturated phenylmorphan 6. Conversion of 6 to oxide-bridged 2d was accomplished in a multistep fashion that utilized the introduction of a bromine atom, followed by O-demethylation of the phenolic methyl ethers and base-catalyzed intramolecular phenoxide displacement of the bromine. Compound (+/-)-2d represents an oxide-bridged derivative of the potent 5-(m-hydroxyphenyl)morphan class of opioid analgesics 1. Unlike the 5-(m-hydroxyphenyl)morphans that have a freely rotating phenyl group, 2d has the phenyl ring conformationally restricted at an angle of 49 degrees relative to atoms 1, 3, 11a, and 12 of 2d. The low binding of (+/-)-2d to rat brain homogenate receptor preparations [IC50 = 1000 nM] may indicate that the phenyl angle of 49 degrees is not suitable for binding to opioid receptors.

Animals↗

Loss of power with flexure of hydrogel plus lenses.

Both clinical impressions and theoretical analysis suggest a slight loss of power with flexure of low-plus-power hydrogel contact lenses. Low-minus-power hydrogel lenses do not appear to change power. This study confirms this effect.

Contact Lenses, Hydrophilic↗

Calculating areal average thickness of rigid gas-permeable contact lenses.

A method to calculate areal average thickness of rigid contact lenses is shown. The method involves division of lens volume, which is determined from lens design specifications or derived from measured lens weight, by the area of the lens back surface. Areal average thickness may then be used with known oxygen permeability to generate oxygen transmissibility values.

Contact Lenses↗

Clinical management of cosmetic extended-wear contact lens failure.

Fifteen patients discontinued use of extended-wear hydrogel contact lenses. The primary cause was neovascularization (60%), although lens soilage, giant papillary conjunctivitis and ulceration were factors in several patients each. All patients were successfully refitted with daily-wear rigid or thin, hydrogel contact lenses following simple clinical techniques.

Adolescent↗

Behavioral studies with anxiolytic drugs. III. Antipunishment actions of buspirone in the pigeon do not involve benzodiazepine receptor mechanisms.

Buspirone, a clinically effective anxiolytic, has not shown robust effects consistently in procedures used traditionally with rodents and nonhuman primates to evaluate potential antianxiety activity. When key pecking by pigeons was maintained by food and was punished alternately under one component of a multiple schedule by the presentation of electric shock (conflict procedure), buspirone (0.03-10.0 mg/kg i.m.) produced increases in punished responding that were up to 30 times those of the control response rate. These doses did not affect or decreased unpunished responding. A buspirone analog, MJ 13805 (gepirone) produced effects similar to buspirone, although unpunished responding was slightly more sensitive to the rate-decreasing effects of MJ 13805 than to those of buspirone. A metabolite of buspirone, 1-pyrimidinyl piperazine (1-PP; MJ 13653), did not affect key pecking across a wide dose range (0.01-3.0 mg/kg i.m.), although slight decreases in both punished and unpunished responding occurred at the highest dose. Increases in punished responding with buspirone were not affected by the benzodiazepine receptor antagonist Ro 15-1788 (0.01-0.1 mg/kg i.m.). [3H]Diazepam binding to pigeon cerebrum or cerebellum in vivo was not altered by buspirone, or did buspirone, MJ 13805, or 1-pyrimidinyl piperazine displace [3H]flunitrazepam binding in vitro at pharmacologically relevant concentrations. These findings confirm previous work demonstrating marked rate-increasing effects of buspirone on punished responding in the pigeon, extend such effects to the buspirone analog MJ 13805 and indicate that the effects of buspirone are not mediated through the benzodiazepine receptor complex.

Animals↗

Theoretical optics of toric hydrogel contact lenses.

Toric hydrogel contact lenses are used when spherical lenses prove inadequate at correcting refractive error due to astigmatism. A model of hydrogel contact lens flexure effects allows theoretical investigation of the in situ optical power of toric soft contact lenses. Total meridional power is believed to be the sum of meridional lens power and entrapped tear layer power if any, and not due to lens form or flexure when considering low-minus powered lenses. The clinician should reduce astigmatic power correction both to allow for minus tear lens effects in thicker meridians and to decrease variable visual results due to misrotation.

Contact Lenses↗

Critical corneal oxygen values: a summary.

Data from several previous studies were collected and analyzed by remeasuring test hydrogel contact lens oxygen transmissibilities (Dk/L) at ocular temperature to arrive at summary critical human pre-corneal oxygen tension (30 mmHg), and required Dk/L (18 X 10(-9) cm ml O2/sec ml mmHg) under open-eye conditions. Estimations for closed-eye (extended wear) conditions were also performed.

Contact Lenses↗

Late evolutionary appearance of 'peripheral-type' binding sites for benzodiazepines.

Four classes of non-mammalian vertebrates were examined for the presence of both 'brain-specific' and 'peripheral-type' binding sites for benzodiazepines in the central nervous system. 'Brain-specific' binding sites for benzodiazepines were found in the central nervous systems of all non-mammalian vertebrates studied. However, in contrast to mammals, either very low or undetectable levels of 'peripheral-type' binding sites for benzodiazepines were observed in the central nervous systems of these non-mammalian vertebrates. Furthermore, the density of 'peripheral-type' binding sites for benzodiazepines in non-mammalian vertebrate heart was less than or equal to 2% of that found in mammalian cardiac tissue. These findings suggest a very late evolutionary appearance of 'peripheral-type' binding sites for benzodiazepines, implying that these sites may have (a) highly specialized function(s) in both peripheral tissues and the central nervous system.

Animals↗