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Biomedical subjects

S E Hall

Publications and source records attributed to S E Hall.

At least 73 records · Page 4Linked to original sources
PubMed1989

9,11-Epoxy-9-homo-14-thiaprost-5-enoic acid derivatives: potent thromboxane A2 antagonists.

A novel bicyclic prostaglandin analogue, (1S)-[1 alpha,2 alpha(Z),3 alpha,4 alpha]-7-[3-[(hexylthio)methyl]-7- oxabicyclo [2.2.1]hept-2-yl]-5-heptenoic acid ((-)-10), and its cogeners were found to be potent antagonists at the TxA2 receptor. Compound (-)-10 was the only stereoisomer out of eight possible structures that was active. Thioether (-)-10 was 30-40-fold more potent than another TxA2 antagonist, BM 13.177, in inhibiting arachidonic acid (AA) induced aggregation of human platelet-rich plasma. Compound (-)-10 was effective (I50 = 0.5 +/- 0.4 microM) in inhibiting 9,11-azo-PGH2-induced (0.1 microgram/mL) contraction of guinea pig tracheal spirals. The bronchoconstriction in anesthetized guinea pigs induced by AA was also effectively antagonized by (-)-10 (1 mg/kg, iv); however, in this assay (-)-10 exhibited some direct agonist activity. Radioligand binding studies in washed (human) platelets revealed that (-)-10 is one of the most potent ligands for the PGH2/TxA2 receptor yet described (Kd = 1.6 +/- 0.4 nM).

Animals↗
PubMed1989

Repetition rate and signal level effects on neuronal responses to brief tone pulses in cat auditory cortex.

This study describes the effects on the spike count, spike timing, and entrainment of cat auditory cortex neurons of parametric variations in the repetition rate and amplitude of a brief, characteristic frequency tone pulse. Data were obtained from single neurons in barbiturate-anesthetized cats to which signals were presented monaurally to the ear contralateral to the recording electrode. All neurons showed low-pass sensitivity to tone repetition rate. In cells with a monotonic rate response, the effect of an increasing stimulus level was to elevate the response rate and to extend performance to higher repetition rates. In nonmonotonic cells, cutoff frequencies (for repetition rate) varied with overall spike count. Latent periods increased with increases in repetition rate. This effect developed over the first few stimulus trials at any given repetition rate. Spike entrainment to the tone pulses varied with both repetition rate and signal level. Increases in signal level improved entrainment for responses to stimuli presented at low repetition rates, but entrainment at high repetition rates always saturated at significantly imperfect levels.

Acoustic Stimulation↗
PubMed1988

Identification of human erythrocyte blood group antigens on decay-accelerating factor (DAF) and an erythrocyte phenotype negative for DAF.

Decay accelerating factor (DAF) is a glycoprotein present on the surfaces of many types ofcells in contact with plasma, including erythrocytes, leukocytes, and platelets (reviewed in reference 1). A small amount of DAF is also present in serum. Numerous investigators have demonstrated that DAF inhibits the action of C3 convertases on cell surfaces, and its absence has been shown to be at least partially responsible for the abnormal sensitivity to lysis by complement exhibited by erythrocytes of patients with the acquired stem cell disorder paroxysmal nocturnal hemoglobinuria (PNH) (2). Hereditary absence of DAF has not been previously described. Tc(a) and Cr(a) are high-frequency human erythrocyte antigens . These antigens are part of a family of blood group antigens, designated Cromer related, which are all absent from the null phenotype cell IFC(-) , or Inab (3). Recently, Spring and colleagues (4) have identified two monoclonal antibodies which bound to high frequency red cell antigens absent from the Inab phenotype. They also demonstrated that these antibodies, as well as several human antisera to Cromer-related antigens, bound to a 70-kD glycoprotein when used to stain immunoblots of human erythrocyte membrane proteins . Because the wide tissue distribution of mAb reactivity, along with some of the biochemical characterization and immunoblotting data, was similar to that of DAF, we investigated whether the Cromer-related antigens Cr(a) and Tc(a) resided on the DAF molecule.

Blood Group Antigens↗
PubMed1988

Pediatric acquired immunodeficiency syndrome with negative human immunodeficiency virus antibody response by enzyme-linked immunosorbent assay and Western blot.

A 5-month-old white girl having persistent oral candidiasis was brought to medical attention because of acute respiratory distress, pneumonia, and hypoxia that worsened despite supportive care and antibiotics. Bronchial lavage fluid yielded Pneumocystis carinii. The diagnosis of acquired immunodeficiency syndrome (AIDS) was suspected, although enzyme-linked immunosorbent assay (ELISA) and Western blot tests were both negative for human immunodeficiency virus (HIV) antibody. Immunologic evaluation included the following results: a low normal CD4/CD8 ratio 0.88, CD4 lymphocytes 493/microL, and elevated IgA 539 mg/dL and IgM 175 mg/dL with normal IgG 492 mg/dL. Lymphocyte stimulation study results were depressed. Lymphocytes sent for culture were subsequently positive for HIV. The mother was HIV antibody positive by enzyme-linked immunosorbent assay and Western blot but belonged to no high-risk group and was asymptomatic except for chronic diarrhea. The father was HIV antibody negative. The patient was treated with pentamidine and IV gamma-globulin with good clinical response and a rapid decrease of IgM and IgA toward normal values. Subsequent candidal pneumonia and candidal esophagitis were treated successfully with amphotericin B. The patient has received prophylactic IV gamma-globulin infusions for 6 months and remains HIV negative by enzyme-linked immunosorbent assay and Western blot. This case of pediatric AIDS highlights the need to consider HIV infection in the differential diagnosis of any child with physical findings or illnesses suggestive of AIDS-related complex or AIDS, even when HIV serologic findings are negative and parents belong to no high-risk group. Parental testing for HIV antibody is suggested in such cases.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Characterization of [5,6-3H]SQ 29,548 as a high affinity radioligand, binding to thromboxane A2/prostaglandin H2-receptors in human platelets.

The binding of 5,6-3H(1S-[1 alpha, 2 beta(5Z), 3 beta, 4 alpha])-7-[3-([2-[(phenyl amino)carbonyl]hydrazino]methyl)-7-oxabicyclo[2.2.1]hept-2-yl]-5- heptenoic acid to receptors in human washed platelets (WP) and platelet membranes (PM) was characterized with regard to kinetics, saturability and competitive inhibition by putative thromboxane A2/prostaglandin H2 (TP)-receptor ligands. Specific binding of [3H]SQ 29,548 routinely amounted to 90 to 97% of total binding. The rate of association was 1.6 x 10(7) and 2.5 x 10(7) M-1 x min-1 in WP and PM, respectively. The corresponding rate of dissociation was 0.07 and 0.12 min-1, resulting in dissociation constants of 4.1 and 5.8 nM in WP and PM, respectively. Saturable binding to a single class of receptors indicated a receptor density of 2633 fmol/mg of protein in WP (1394 receptors/platelet; kd, 4.5 nM) and 1466 fmol/mg of protein in PM (kd, 11.3 nM). Specific binding of [3H]SQ 29,548 was inhibited by five antagonists (high/low affinity kd values in nanomolar), SQ 29,548 (WP, 5.2; PM, 7.3), SQ 28,668 (WP, 32; PM, 73), SQ 30,741 (WP, 28; PM, 50), BM 13,177 (WP, 140; PM, 4834) and BM 13,505 (WP, 5/379; PM, 11). Two agonists, U 44069 and U 46619, inhibited the binding in a biphasic manner, indicating binding to two receptor sites (approximately 20/80%) with kd values of 4/72 and 4/170 nM, respectively, in WP and 7/136 and 19/502 nM, respectively in PM. The demonstrated high affinity binding of [3H]SQ 29,548 to human platelet TP-receptors should make this radioligand a suitable and potentially useful tool in future studies of function, structure and regulation of TP-receptors.

Binding Sites↗
PubMed1987

Responses of single neurons in cat auditory cortex to time-varying stimuli: linear amplitude modulations.

Single neurons in the auditory cortex of anesthetized cats were examined quantitatively for their sensitivity to the sound pressure level of characteristic frequency (CF) tone pulses, and to 6 dB, linear modulations in the amplitude of a continuous CF carrier tone. The direction and rate of amplitude modulation (AM), and the carrier level on which it was imposed, were manipulated parametrically. Studied with amplitude modulations, the majority of neurons responded only to intensity increments. The minimum carrier level upon which an amplitude modulation was able to evoke spike discharges was typically comparable to the tone pulse threshold SPL. For many neurons, an "intensity increment response area", i.e., the domain of AM rate and carrier level conjunctions within which a 6 dB AM was able to evoke discharges, could be delimited. For many neurons, preferred rate of AM drifted from high to low with increases in the carrier level on which the modulation was imposed. The most vigorous responses to AM stimuli often occurred when the carrier levels were associated with the rising slope or the peak of the tone pulse rate intensity function. It may be possible to understand the general form of AM response areas in terms of short-term adaptation, the disposition of excitatory and inhibitory tone pulse response areas, and the spectra of the AM stimuli used.

Acoustic Stimulation↗
PubMed1986

Inhibition of prostaglandin biosynthesis by SQ 28,852, a 7-oxabicyclo[2.2.1]heptane analog.

7-Oxabicyclo[2.2.1]heptane analogs of prostaglandin (PG) H2 can act as thromboxane (Tx) A2 receptor antagonists or agonists, PGI2 and/or PGD2 receptor agonists, or exhibit a mixture of the above activities. SQ 28,852, a new analog with a hexyloxymethyl omega side chain, is a potent inhibitor of PG synthesis. SQ 28,852 inhibited collagen and arachidonic acid (AA)-induced platelet aggregation and TxB2 and PGE2 formation, but did not block platelet aggregation induced by ADP or the TxA2 mimics, 9,11-azo PGH2, SQ 26,655, and U-46,619. It also blocked conversion of AA to TxB2, PGE2, and 6-keto PGF1 alpha by microsomal preparations of human platelets, bovine seminal vesicles, and bovine aortas, respectively, but did not inhibit the conversion of PGH2 to TxA2 by the platelet microsomal preparation. SQ 28,852 (p.o.) protected mice against the lethal effects of AA (75 mg/kg, i.v.). The I50 values for SQ 28,852, indomethacin and aspirin were 0.025, 0.05 and 15 mg/kg, respectively. Neither SQ 28,852 nor indomethacin protected mice from death caused by 9,11-azo PGH2. SQ 28,852 (0.01 to 1 mg/kg, i.v.) inhibited AA-induced bronchoconstriction in anesthetized guinea pigs for at least 60 min. As an inhibitor of AA-induced bronchoconstriction, SQ 28,852 was 16- and 45-times more potent than indomethacin at 3 and 60 min after i.v. administration, respectively. SQ 28,852 did not inhibit bronchoconstriction induced by histamine or 9,11-azo PGH2, indicating its specificity of action in vivo. SQ 28,852 is the first example of a new class of cyclooxygenase inhibitors whose structure is similar to that of the naturally occurring endoperoxide, PGH2.

Animals↗
PubMed1986

The laminar distributions and postnatal development of neurotransmitter and neuromodulator receptors in cat visual cortex.

We review efforts to further understand the development and nature of sensory processing mechanisms in the cat visual cortex. In vitro autoradiographic and homogenate assay techniques have been employed to determine the laminar distribution and characteristics of various neurotransmitter and neuromodulator receptor populations during postnatal development. Each receptor population shows a distinct laminar-specific pattern of binding, which, in most cases, is age-dependent. Changes in receptor number and affinity are also observed during postnatal development. These findings indicate that major alterations in the basic chemical circuitry of cat visual cortex are a normal feature of postnatal maturation and may play a role in plasticity mechanisms.

Aging↗
PubMed1986

9,11-Epoxy-9-homo-14-oxaprosta-5-enoic acid derivatives. Novel inhibitors of fatty acid cyclooxygenase.

A novel bicyclic prostaglandin analogue, [1R-[l alpha,2 beta (5Z),3 beta,4 alpha]]-7-[3-[(hexyloxy)methyl]- 7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (1), and cogeners were found to be potent inhibitors of fatty acid cyclooxygenase. Compound 1 was the only stereoisomer out of eight possible structures that was active. Ether 1 was 20 times more potent than indomethacin (IND) in inhibiting arachidonic acid (AA) induced aggregation of human platelet-rich plasma. Compound 1 was also more potent than IND in several in vivo assays, AA-induced sudden death in the conscious mouse (2 times) and AA-induced bronchoconstriction in the anesthetized guinea pig (16-45 times).

Arachidonic Acid↗
PubMed1986

Spike-rate intensity functions of cat cortical neurons studied with combined tone-noise stimuli.

In the auditory cortex of anesthetized cats, single neurons were studied for their sensitivity to tones presented against backgrounds of continuous wide-spectrum noise. Tone pulses and noise stimuli were mixed acoustically and presented using calibrated, sealed stimulating systems. Data collected were spike-rate intensity functions for tones delivered alone and in the presence of noise. In most neurons, noise of any given intensity induced tone sensitivity shifts that were greatest for frequencies to which the neurons were most sensitive. When the sensitivity loss was in excess of about 15 dB, continuous noise usually caused a steepening of the slope of the tone intensity function. These data suggest that the excitatory response area of a cortical neuron is shaped by multiple, incompletely overlapping inputs of varying sensitivities. In the presence of a continuous noise mask, the disparate thresholds of these inputs may be brought into closer register, resulting in a steepened rate intensity function. These observations may be germane to the neural genesis of the "recruitment" seen in the loudness judgments of normal listeners for masked tones.

Acoustic Stimulation↗
PubMed1986

Characterization, distribution, and ontogenesis of adenosine binding sites in cat visual cortex.

In vitro autoradiographic techniques were used to characterize binding sites for 3H-cyclohexyladenosine (CHA) and 3H-5'-N-ethylcarboxamidoadenosine (NECA) in cat and kitten visual cortex. 3H-CHA binding sites in adult cat have a Bmax of 1,363 fmol/mg protein and a Kd of 6.8 nM. Displacement experiments indicate that 3H-CHA binds to an adenosine receptor similar to the A1-adenosine receptor described by other investigators. 3H-NECA binding sites in adult cat have a Bmax of 518 fmol/mg protein and a Kd of 15.4 nM. Displacement experiments do not allow us to identify this binding site unambiguously. Bmax values increase during postnatal development for both binding sites, peaking in adulthood for 3H-CHA and at 30 d for 3H-NECA. Kd values show neither consistent nor significant differences during postnatal development for either binding site. 3H-CHA and 3H-NECA binding sites are concentrated in layers 1-3 and upper layer 5 in the visual cortex of adult cats. These laminar patterns, however, change during postnatal development, showing the densest binding in the deep cortical layers (5 and 6) in kittens younger than 30 d of age and a fairly homogeneous binding in older kittens before achieving the adult distribution.

Animals↗
PubMed1986

Separation of the acetylcholinesterase-deficient red cells in paroxysmal nocturnal hemoglobinuria.

Blood of patients with paroxysmal nocturnal hemoglobinuria (PNH) most often contains two or more populations of erythrocytes--one population with normal sensitivity to lysis by complement (PNH I cells) and a second population of moderately abnormal cells (PNH II cells) or markedly abnormal cells (PNH III cells). PNH II and III cells exhibit moderately and markedly increased sensitivity to lysis by complement, respectively, as well as other membrane defects. We have devised a method for isolating pure, intact PNH II and III cells from mixed populations by use of monoclonal antibodies and cell affinity chromatography. Study of purified cell populations has led to the identification of a further subtype, PNH IIIb, of PNH erythrocytes. PNH IIIb erythrocytes are less sensitive to complement lysis than PNH IIIa cells but are lysed by fluid-phase activation of complement, unlike PNH II erythrocytes.

Acetylcholinesterase↗
PubMed1984

Ketone body kinetics in humans: the effects of insulin-dependent diabetes, obesity, and starvation.

The kinetics of acetoacetate (A) and beta-hydroxybutyrate (B) have been studied following the injection as a pulse or continued infusion of [3-14C]acetoacetate (A*) or [14C]beta-hydroxybutyrate (B*) into six newly diagnosed, untreated, ketotic diabetic patients, ten obese subjects in the postabsorptive state, and the ten obese subjects after 1-2 weeks starvation (50 cal per day). Employing a compartmental model of acetoacetate and beta-hydroxybutyrate kinetics developed using CONSAM for normal subjects, the rate coefficients (Lij), rates of release of newly synthesized acetoacetate and beta-hydroxybutyrate into the blood (UA, UB), and fractional removal of each compound (FCRA and FCRB) were calculated. Ketone body release into blood (UA + UB) in diabetic subjects was threefold higher than normal (mean +/- SD, 208 +/- 118 versus 81 +/- 66 mumol min-1 m-2) and in obese subjects the rate increased on starvation from 171 +/- 70 to 569 +/- 286 mumol min-1 m-2. In each case most of the increase was in beta-hydroxybutyrate. The major change in diabetes and on starvation of the obese subjects was in the rate coefficient for removal of ketone bodies. Normally 0.168 +/- 0.109 min-1, it was 0.055 +/- 0.040 min-1 in the diabetic patients and fell from 0.066 +/- 0.040 to 0.027 +/- 0.019 min-1 in the obese subjects on starvation. In normal subjects, FCRA was similar to FCRB (0.226 +/- 0.142 versus 0.188 +/- 0.124 min-1). However, in diabetics, FCRA was 0.074 +/- 0.044 and FCRB was 0.050 +/- 0.034 min-1 and both were lower than normal. On starvation of obese subjects, FCRA fell from 0.199 +/- 0.047 to 0.089 +/- 0.035 min-1, whereas FCRB fell from 0.141 +/- 0.040 to 0.033 +/- 0.012 min-1. Therefore, the removal of beta-hydroxybutyrate was impaired more than that of acetoacetate in all patients. Our results confirm previous observations that ketosis is associated with high rates of ketogenesis and a decrease in fractional clearance. In addition, we found that in diabetes, obesity, and in obese subjects following starvation, most of the increased synthesis was in beta-hydroxybutyrate and that the clearance of beta-hydroxybutyrate decreased more than that of acetoacetate.

3-Hydroxybutyric Acid↗
PubMed1984

Ketone body kinetics in humans: a mathematical model.

A model has been developed to account for ketone body kinetics in man based on data following bolus injections of [14C]acetoacetate (A) and [14C]beta-OH butyrate (B) into normal humans in the postabsorptive state. The model consists of separate compartments for blood A and B that are linked by a tissue compartment in which rapid interconversion of the ketone bodies occurs. The probability of movement from blood into this compartment was assumed to be the same for both ketone bodies. Two slowly equilibrating tissue compartments are required to account for the slow components in the tracer data, and thus a five-compartment model is proposed. By modeling the transient tracer data with the tracee in a steady state, ketone body kinetics were defined in terms of the rapid interconversions of A and B, and the slow exchanges of carbon within the tissues. The rates of release of new A and B into blood, (UA and UB) were calculated. These rates were less than the apparent production rates, PRA and PRB, as the PR's included carbon atoms first released as the other ketone body. The exchange constants between the compartments were determined in addition to the fractional catabolic rates (FCR) and metabolic clearance rates (MCR) of A and B. The initial space of distribution was 10 L and the mean values +/- SD (n = 11), normalized to this volume, were UA = 6.4 +/- 5.0, UB = 8.8 +/- 8.0 (mumol L-1 min-1), FCRA = 0.226 +/- 0.142, FCRB = 0.188 +/- 0.124 (min-1), MCRA = 2.26 +/- 1.42, MCRB = 1.87 +/- 1.23 (L min-1) and PRA = 11.1 +/- 7.6, PRB = 12.7 +/- 10.0 (mumol L-1 min-1).

3-Hydroxybutyric Acid↗
PubMed1983

Sepsis with coagulase-negative staphylococci in critically ill newborns.

Coagulase-negative staphylococci are infrequently recognized as pathogens responsible for life-threatening nosocomial infections in high-risk neonates. To determine the incidence, appearance, and antibiotic sensitivity of infections with these organisms, 416 infants were surveyed. Fifty infants (12%) had blood cultures positive for coagulase-negative Staphylococcus. Fourteen cultures (13 infants; mean birth weight +/- SD, 1.91 +/- 1.13 kg; gestational age +/- SD, 34 +/- 6 weeks) were identified as representing true bacteremia (pure growth of the organism in both bottles of one or more blood cultures exhibiting identical antibiotic sensitivities). Twelve cultures exhibited clinical signs of sepsis, and WBC counts were suggestive of sepsis in seven cases. Thirteen organisms were penicillin resistant, eight were oxacillin resistant, and all were sensitive to vancomycin. Coagulase-negative staphylococci are currently the most common nosocomial pathogens at our hospital. Therapy for suspected coagulase-negative staphylococcal sepsis should include vancomycin hydrochloride.

Coagulase↗
PubMed1983

Adult age differences in the use of story structure in delayed free recall.

Thirty-six young adults (M age = 24.3 years) and 36 old adults (M age = 71.8 years) listened to four double-episode stories having either standard, interleaved, or scrambled structure. Two days later they were asked to recall the stories. Analysis of the mean number of nodes recalled revealed no age differences in the recall of standard and scrambled stories with both groups recalling the standard stories equally well and the scrambled stories equally poorly. However, for interleaved stories, young adults followed their pattern of recall for standard stories while old adults followed their pattern for scrambled stories. Also, the age groups differed in their pattern of additions and distortions, with old adults giving more for standard stories and young adults giving more for scrambled stories. Results appear to support models of age-related differences in memory processes and/or strategies when material must be reorganized or hierarchized. Possible metacognitive differences were also discussed; i.e., old adults may aim to tell the story interestingly, while young adults aim to tell it accurately.

Adolescent↗
PubMed1982

Isotope turnover studies in uncontrolled diabetes and the effects of insulin.

Turnover rates of glucose, free fatty acids (FFA) and leucine have been measured in newly diagnosed, uncontrolled insulin-dependent diabetic (IDD) patients. The results have been compared with data collected from the same patients while on conventional insulin therapy as well as after overnight intravenous infusion of insulin with sustained normoglycaemia. The data have been analysed by compartmental and non-compartmental methods and the results have been compared with simultaneously collected data on respiratory exchange. Oxidation rates of 14C-labelled substrates have also been measured. Tracer studies were done on established diabetics after insulin withdrawal and subsequent intravenous infusion of insulin at different rates. The results confirm the in vivo importance of the glucose-fatty acid cycle, indicating that when glucose, FFA and ketone bodies are available in excess it is FFA and ketones that are metabolized in preference to glucose. The data emphasize the importance of increased production rates rather than decreased utilization rates in producing high concentrations of substrates in the plasma of insulin-deficient patients.

Blood Glucose↗