Biomedical subjects

L Marshall

Publications and source records attributed to L Marshall.

At least 73 records · Page 4Linked to original sources

PubMed1992

Estimation of psychometric functions from adaptive tracking procedures.

Because adaptive tracking procedures are designed to avoid stimulus levels far from a target threshold value, the psychometric function constructed from the trial-by-trial data in the track may be accurate near the target level but a poor reflection of performance at levels far removed from the target. A series of computer simulations was undertaken to assess the reliability and accuracy of psychometric functions generated from data collected in up-down adaptive tracking procedures. Estimates of psychometric function slopes were obtained from trial-by-trial data in simulated adaptive tracks and compared with the true characteristics of the functions used to generate the tracks. Simulations were carried out for three psychophysical procedures and two target performance levels, with tracks generated by psychometric functions with three different slopes. The functions reconstructed from the tracking data were, for the most part, accurate reflections of the true generating functions when at least 200 trials were included in the tracks. However, for 50- and 100-trial tracks, slope estimates were biased high for all simulated experimental conditions. Correction factors for slope estimates from these tracks are presented. There was no difference in the accuracy and reliability of slope estimation due to target level for the adaptive track, and only minor differences due to psychophysical procedure. It is recommended that, if both threshold and slope of psychometric functions are to be estimated from the trial-by-trial tracking data, at least 100 trials should be included in the tracks, and a three- or four-alternative forced-choice procedure should be used. However, good estimates can also be obtained using the two-alternative forced-choice procedure or less than 100 trials if appropriate corrections for bias are applied.

Attention↗

PubMed1992

Evaluate health plans.

For most benefits administrators, this program probably does not automate a function they are now doing manually, but it does bring a consultant/broker function in-house (although this is only one of many such functions). In some organizations, particularly smaller ones that might skimp on analysis of their health plans before negotiating carrier rate changes each year, it might mean that such analysis actually does take place. But it you are a benefits administrator who has been performing yearly, manual evaluations of your plans, be very careful about trying and demonstrating this software. If you think you might not be granted approval by management to purchase it, you may wish you didn't know how well it works.

Evaluation Studies as Topic↗

PubMed1991

Regulation of intracellular acetyl-CoA carboxylase by ATP depletors mimics the action of the 5'-AMP-activated protein kinase.

Acetyl-CoA carboxylase (ACC) can be regulated in vitro via phosphorylation by a 5'-AMP-activated protein kinase. A potential intracellular role for this kinase has been studied in the Fao hepatoma cell by manipulating the intracellular adenine nucleotide pool with ATP-depleting agents. Three different ATP depletors, antimycin A, dinitrophenol, and sodium azide, all promote the rapid loss of ACC activity characterized by a marked reduction in enzyme Vmax, abolition of citrate-independent activity, an increase in the Ka for citrate and a reduction in the mass of a complex between the two major ACC isozymes. These effects persist through enzyme purification on monomeric avidin-Sepharose and are accompanied by an increase in 32P-content, both consistent with depletor-induced covalent enzyme modification. The effects of ATP depletors in intact cells are mimicked in vitro on phosphorylation of ACC by the 5'-AMP-activated protein kinase and are reversible on dephosphorylation. These data indicate that ACC activity is sensitive to the intracellular adenylate charge, but that changes in the state of enzyme phosphorylation, rather than direct allosteric regulation by adenine nucleotides, underly this mode of enzyme control. This kinase-mediated modulation provides a mechanism for altering the rate of fatty acid synthesis and, secondarily, fatty acid oxidation, depending on the rate of ATP generation from carbohydrate-derived precursors in several tissues in vivo.

AMP-Activated Protein Kinases↗

PubMed1991

The development of competence in resting B cells. The induction of cyclic AMP and ornithine decarboxylase activity after direct contact between B and T helper cells.

In the present communication, an experimental approach is utilized that facilitates the study of biochemical processes induced in B cells after their interaction with Th cells. In this approach, Th cell clones are stimulated for 18 h upon anti-CD3-coated plates, fixed with paraformaldehyde, and added at a 2 to 3:1 ratio to small, resting B cells (isolated from Percoll gradients). Th cells not stimulated on anti-CD3-coated plates, but fixed with paraformaldehyde, serve as controls for these experiments. The activated, fixed Th cells induce a transient, sixfold increase in B cell levels of cAMP, as well as an increase in B cell expression of ornithine decarboxylase (ODC) activity. This enzyme initiates the synthesis of polyamines and has been shown to be increased as cells enter the growth phase. In addition, previous studies have shown that the cellular levels of ODC activity are controlled by a multi-tiered regulatory cascade. To examine this aspect, polyclonally stimulated B cells were studied. Such cells demonstrated a gradual increase in ODC mRNA levels that peaked between 6 and 15 h and can be partially explained by a three- to fourfold increase in mRNA stability but not by changes in the enzyme affinity for substrate. The increase in ODC mRNA occurs in the absence of protein synthesis, suggesting that the ODC gene is a member of the immediate/early gene family. Finally, the early increase in ODC mRNA was enhanced in cells in which cAMP levels were artificially elevated, suggesting the possibility that the cAMP-dependent signaling pathway participates during the regulation of this gene expression. The significance of these experimental results concerning the process of B cell activation is discussed.

Animals↗

PubMed1991

Decision criteria for pure-tone detection used by two age groups of normal-hearing and hearing-impaired listeners.

Response criteria from a yes-no task and detection thresholds from two test procedures were measured for four groups of adults: younger normal-hearing, older normal-hearing, younger hearing-impaired, and older hearing-impaired. The two test procedures were an audiological procedure (which does not control for response bias) and a 21FC adaptive procedure (which does control for bias). The signal was a 500 or 4000 Hz tone presented in quiet. All four groups showed an equally conservative response bias in the yes-no task. In addition, neither age nor hearing loss affected the difference (6.5 dB) between the two threshold measures.

Adolescent↗

PubMed1991

An interleaved tracking procedure to monitor unstable psychometric functions.

In some experimental situations, the psychometric function underlying performance may not be stable, but instead may shift along the stimulus axis in response to changes in attention, learning, or task difficulty. When this occurs, the measured threshold may be influenced and the slope of the measured function will be inaccurately shallow. With commonly used experimental procedures, it is difficult to know whether a shallow psychometric function slope is a true reflection of the sensory process, or is a result of "averaging" a highly variable underlying function. Here, a new method is described of estimating psychometric function slope from the variability in two interleaved adaptive tracks, consulted on alternate trials, that is resistant to the effects of shifting performance levels. Further, a mechanism is described for assessing the likelihood that a threshold was, in fact, stable over the course of its measurement. Computer simulations are reported as well as verification of the method in measurements of human performance on a psychophysical task. Several conditions of externally imposed variability were simulated to establish the ability of these procedures to identify unstable functions and produce accurate slope estimates. The procedures worked well for thresholds shifting by as little as 4 dB if the variation did not occur too rapidly. The procedure and associated analyses are recommended as a relatively "free" means of calculating slope and quantifying threshold reliability with little extra experimental effort.

Attention↗

PubMed1990

Neuromodulatory regulation of gonadotropin-releasing hormone pulsatile discharge in women.

The pulsatile release of gonadotropin-releasing hormone and the consequent secretion of gonadotropins are regulated by a complex interplay of steroids, neuropeptides, catecholamines, and environmental factors. Estrogen and progesterone influence the amplitude and frequency of luteinizing hormone pulsatile secretion. These effects lead to both a diurnal variation in pulse frequency, with a lower frequency at night, and variation during the menstrual cycle, with a lower frequency and increased amplitude during the luteal phase. Opioid peptides inhibit the pulsatile discharge of gonadotropin-releasing hormone and luteinizing hormone. The opioid antagonist, naloxone, causes an increase in luteinizing hormone secretion, particularly during the luteal phase. The administration of opioid receptor agonists, such as beta-endorphin, results in a decline in serum luteinizing hormone during the early follicular phase. Corticotropin-releasing factor, which is increased during stress, inhibits pulsatile luteinizing hormone secretion, and this effect can be blocked by the simultaneous administration of naloxone. These observations suggest that corticotropin-releasing factor exerts its effects on luteinizing hormone through an opioidergic intermediary. Endogenous catecholamines such as dopamine inhibit pulsatile luteinizing hormone release; however, the mechanism involved is not clear.

Adult↗

PubMed1990

Head injury: an immunologic deficit in T-cell activation.

Despite progress in the management of increased pressure following head injury, infection remains the most common complication in survivors. This study attempted to better define the immunologic deficit that occurs immediately and in the early post-recovery period following severe head injury. Twenty-seven patients admitted with the primary diagnosis of severe head injury (mean Glasgow Coma Score, 6.75) were studied within 24 hours of injury and at weekly intervals. T-cell proliferative response to mitogen stimulation was assessed. T-cell antigen expression following PHA stimulation was assessed for helper (CD4) and suppressor (CD8) subpopulations: the early T-cell activation antigens interleukin-2 receptor (IL2R) and transferrin receptor (TFR), and the late antigen (HLA-DR) using flow cytometry. Polymorphonuclear leukocyte function was assessed using oxidative burst. There was a reduction in the proliferative response of T cells to mitogen stimulation. The B-cell response seemed unaffected. The diminished proliferative response was accompanied by diminished expression of early activation antigens (IL2R and TFR) and late (following DNA synthesis) (HLA-DR). This was seen primarily on helper/inducer cells (CD4+). Polymorphonuclear leukocyte function was unaffected.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1989

Cognate interactions between helper T cells and B cells. III. Contact-dependent, lymphokine-independent induction of B cell cycle entry by activated helper T cells.

An Ag-specific, IL-2-dependent Th clone induced the growth of B cells in a class II-restricted, Ag-specific, IL-2-dependent manner. The formation of stable Th-3.1-B cell conjugates was restricted by Ag and class II MHC. After activation of Th-3.1 by insolubilized anti-T3 (Th-3.1T3), Th-3.1T3 induced the growth of B cells in a class II unrestricted, Ag nonspecific manner. The formation of stable conjugates between Th-3.1T3 and B cells was also class II unrestricted and Ag nonspecific. Although the interaction of Th-3.1T3 and B cells was class II unrestricted, the interaction was inhibited by the combination of anti-IA and anti-IE mAb. This suggested that monomorphic domains of class II MHC molecules were involved in Th-3.1T3-B cell interaction. Fixed Th-3.1T3 but not fixed resting Th-3.1 induced B cell cycle entry, as measured by an increase in B cell RNA synthesis. Trypsin-treatment of Th-3.1T3 before fixation reduced their ability to activate B cells, indicating that cell surface proteins on Th-3.1T3 were required for enhanced B cell RNA synthesis. Anti-IL-4, anti-IL-2R, or anti-IFN-gamma did not affect the ability of Th-3.1T3 to induce heightened B cell RNA synthesis. Progression into S phase by B cells activated with fixed Th-3.1T3 was supported by the addition of soluble factors. When stimulated with fixed Th-3.1T3, EL4 supernatant (SN) enhanced B cell DNA synthesis. Depletion of IL-4, but not IL-2, from EL4 SN ablated its supportive capabilities. IL-4 alone was completely ineffective in supporting entry into S phase. Therefore, IL-4 and another activity(ies) in EL4 SN were necessary for B cell cycle progression into S phase. Taken together, these data suggest that after Th activation, Th cell surface proteins are expressed that mediate the binding of Th to B cells via recognition of nonpolymorphic domains of class II MHC molecules. Contact of Th-3.1T3 with B cells, not lymphokines, results in the entry of B cells into the cell cycle and heightened B cell lymphokine responsiveness. The addition of exogenous lymphokines supports the progression of Th-3.1T3-activated B cells into S phase.

Animals↗

PubMed1989

Evaluation of stopping rules for audiological ascending test procedures using computer simulations.

Stopping rules for ascending audiological test procedures were evaluated by Monte Carlo simulation. The stopping rules differed in the minimum number of responses required at a level, whether these responses occurred on half or a majority of the ascending series, and whether all or only the most recent ascending series were considered. For all procedures, shallow psychometric function slopes yielded estimated thresholds closer to the level giving 50% detection than did steeper slopes, which yielded estimated thresholds roughly 2.5 dB above the level corresponding to 50% on the psychometric function. Shallow slopes also resulted in decreased reliability across threshold measurements, an increased number of trials required for threshold estimates, and a higher proportion of measurements that had to be repeated. Stopping rules using a two-response criterion were faster than those using a three-response criterion, with only a small decrease in reliability. Among stopping rules using the same number of responses for criterion, differences were seen primarily in efficiency for shallow slopes, particularly for procedures using a three-response rather than a two-response criterion for stopping. Results from these simulations should be useful to standards groups.

Audiometry↗

PubMed1989

D-dimer levels in blood salvage for autotransfusion.

Autotransfusion of operatively salvaged blood is an increasingly attractive and used practice. The fear of precipitating a coagulopathy, however, has retarded the acceptance of autotransfusions and the efficiency and convenience of banked homologous blood has proved too competitive in recent years. The risk of transmitting diseases with bank homologous blood has seen a resurgence in the development of autotransfusion. The current alternatives to pre-operative autologous banking or dilution are the reinfusing of filtered salvaged blood, and of blood which has been further processed by washing which involves the extra cost of time, personnel and equipment. Washing removes possible harmful products, but also removes coagulation factors. D-Dimer levels were estimated by monoclonal antibody techniques in salvaged blood before and after washing in 10 patients undergoing aortic surgery and in 10 u of homologous banked blood. The D-Dimer levels in the unwashed blood were increased 85 times, but were normal in the washed blood. D-Dimers are an indication of activation of the coagulation and fibrinolytic systems and the presence of fibrin degradation products.

Aorta↗

PubMed1988

GTP analogues promote release of the alpha subunit of the guanine nucleotide binding protein, Gi2, from membranes of rat glioma C6 BU1 cells.

The major pertussis-toxin-sensitive guanine nucleotide-binding protein of rat glioma C6 BU1 cells corresponded immunologically to Gi2. Antibodies which recognize the alpha subunit of this protein indicated that it has an apparent molecular mass of 40 kDa and a pI of 5.7. Incubation of membranes of these cells with guanosine 5'-[beta gamma-imido]triphosphate, or other analogues of GTP, caused release of this polypeptide from the membrane in a time-dependent manner. Analogues of GDP or of ATP did not mimic this effect. The GTP analogues similarly caused release of the alpha subunit of Gi2 from membranes of C6 cells in which this G-protein had been inactivated by pretreatment with pertussis toxin. The beta subunit was not released from the membrane under any of these conditions, indicating that the release process was a specific response to the dissociation of the G-protein after binding of the GTP analogue. Similar nucleotide profiles for release of the alpha subunits of forms of Gi were noted for membranes of both the neuroblastoma x glioma hybrid cell line NG108-15 and of human platelets. These data provide evidence that: (1) pertussis-toxin-sensitive G-proteins, in native membranes, do indeed dissociate into alpha and beta gamma subunits upon activation; (2) the alpha subunit of 'Gi-like' proteins need not always remain in intimate association with the plasma membrane; and (3) the alpha subunit of Gi2 can still dissociate from the beta/gamma subunits after pertussis-toxin-catalysed ADP-ribosylation.

Animals↗

PubMed1988

Injuries related to all-terrain vehicular accidents: a closer look at head and neck trauma.

Morbidity and mortality associated with all-terrain vehicular accidents is climbing at a steady rate. These accidents frequently result in multiorgan system trauma. A retrospective study of all victims involved in three-wheel motor vehicle accidents admitted to the UCSD Trauma Unit between July 1980 and July 1985 is presented. Injury severity was assessed using the Abbreviated Injury Scale (AIS) and the Injury Severity Score (ISS). The average patient age was 23.3 years with 30% under 16 years of age. There was a male to female ratio of 14:1. The average hospital stay was 12.4 days. Six percent died as a result of their injuries. Injuries to the head and neck were sustained by 83.3% of patients, facial injuries by 46.6%, injuries to the chest by 13.3%, and injuries to the pelvis and abdomen by 13.3%. Thirty percent suffered injuries to the extremities and over 50% had abrasions, contusions, and/or lacerations. Physicians, the public, and state and federal agencies are urged to promote safer use of these recreational vehicles.

Accidents↗

PubMed1988