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Biomedical subjects

M Davis

Publications and source records attributed to M Davis.

At least 325 records · Page 18Linked to original sources
PubMed1993

Pharmacological analysis of fear-potentiated startle.

1. The potentiated startle paradigm measures conditioned fear by an increase in the amplitude of a simple reflex (the acoustic startle reflex) in the presence of a cue previously paired with shock. This paradigm offers a number of advantages as an alternative to most animal tests of fear or anxiety because it involves no operant and is reflected by an enhancement rather than a suppression of ongoing behavior. 2. A variety of drugs which block anxiety in people block fear-potentiated startle in rats. Although the 5-HT1A agonist buspirone is especially effective in blocking fear-potentiated startle, more selective 5-HT1A agonists have been less consistently effective. However, when these drugs are combined with only partially effective doses of the D1 antagonist, SCH23390, a full blockade of fear-potentiated startle is achieved. Hence, synergistic actions appear to occur between serotonin and dopamine in modulating the expression of fear-potentiated startle. 3. In addition to pharmacological studies, physiological studies are being used to define the neural pathways necessary for a visual conditioned stimulus to alter the acoustic startle reflex. The current working hypothesis is that the conditioned stimulus activates the central nucleus of the amygdala through a pathway involving the lateral geniculate nucleus, perirhinal cortex, and lateral and basolateral amygdaloid nuclei. The central nucleus of the amygdala then projects directly to the acoustic startle pathway so as to modulate the startle response. Chemical or electrolytic lesions of either the central nucleus or the lateral and basolateral nuclei of the amygdala block the expression of fear-potentiated startle. These latter amygdaloid nuclei may actually be the site of plasticity for fear conditioning, because local infusion of the NMDA antagonist AP5 blocks the acquisition but not the expression of fear-potentiated startle. 4. Finally, we have begun to investigate brain systems that might be involved in the inhibition of fear. Local infusion of AP5 into the amygdala was found to block the acquisition of experimental extinction, a prototypical method for reducing fear. We have also established a reliable procedure for producing conditioned inhibition of fear-potentiated startle and hope to eventually understand the neural systems involved in this phenomenon.

Acoustic Stimulation↗
PubMed1993

Monte Carlo fluorescence verification of experimental results for the combined ultrasonic and spectroscopic imaging of coronary artery disease.

A system is being tested that combines fluorescence spectroscopy and intravascular ultrasound to image both chemical composition and structure of arterial tissue in vitro. In this system, distances obtained from A-mode ultrasound will be used to compensate for decreases in fluorescence intensity due to the detector-sample separation distance r. For concentrated rhodamine, a fluorescent dye, compensation has been experimentally achieved assuming fluorescence is emitted isotropically and decreases as 1/r2. For dilute rhodamine and human arterial tissue, however, compensation must be achieved with different models, since light penetration into the sample is more significant. Using optical properties consistent with those of the aforementioned samples, experimental results are successfully simulated with a Monte Carlo model for tissue fluorescence. Angular profiles are presented that demonstrate the quantitative difference between the fluorescence of these mediums. The profiles support the hypothesis that, although fluorescence is emitted isotropically within tissue, the angular distribution of light exiting the tissue is not isotropic due to reabsorption events.

Aorta↗
PubMed1993

Determinants of participation in state-of-the-art cancer prevention, early detection/screening, and treatment trials among African-Americans.

It has been suggested that the greatest potential for reducing cancer mortality in high-risk populations may be realized through aggressive implementation of prevention, diagnostic, and state-of-the-art treatment programs and increasing participation in cancer trials. However, the national data suggest that African-Americans are most often underrepresented in such programs and/or trials. Multiple factors are assumed to contribute to this situation, but currently few studies have been conducted to validate their influence. A study focused on identifying factors that contribute to participation of African-Americans in investigational cancer programs and/or trials was therefore conducted. Two hundred twenty African-American men and women were recruited to participate in a regional survey. There was evidence to support the impact that perceptions, attitudes, and beliefs have on willingness to participate in investigational programs and/or trials. The factor having the greatest influence on willingness to participate in investigational programs and/or trials was perceived efficacy of the investigational programs and/or trials. Among this sample there was an apparent hesitancy of many to participate in research programs and/or trials. The prevailing belief that such programs and/or trials were only for those with the disease or condition under study appeared to influence their response. However, when provided information on the opportunities for participation in prevention, diagnostic, and treatment programs and/or projects for those within the general community (especially for those at higher risk) and on the benefits of participation, a much greater willingness to participate was expressed by participants.

Adolescent↗
PubMed1993

Sustaining safe sex: a longitudinal study of a sample of homosexual men.

OBJECTIVE: TO assess the maintenance of safe sexual practice. (We use the term 'safe' sex throughout the paper, since 'safe' is the term adopted by the Australian National Committee on AIDS). DESIGN: Maintenance was assessed by comparing sexual behaviour with both regular and casual partners reported in a 1986/1987 survey (time 1) with behaviour reported in a second survey in 1991 (time 2). METHOD: The 145 homosexually active participants were a non-clinical sample recruited in 1986/1987 by advertisement and followed-up in 1991. A structured questionnaire was administered at both times. Items included questions about the nature of the men's sexual relationships and their sexual practices. RESULTS: Our findings indicate that the majority of men had sustained safe sex practices. HIV prevention strategies adopted included condom use, avoidance of anal intercourse and negotiated safety (i.e., the negotiated practice of unprotected anal intercourse within regular partnerships of concordant serostatus). CONCLUSIONS: Negotiated safety is not the same as relapse.

AIDS Serodiagnosis↗
PubMed1992

A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells.

Human cytomegalovirus (HCMV) is a major pathogen in immunosuppressed individuals, including patients with acquired immune deficiency syndrome. The nucleoside analogue ganciclovir (9-(1,3-dihydroxy-2-propoxymethyl)-guanine) is one of the few drugs available to treat HCMV infections, but resistant virus is a growing problem in the clinic and there is a critical need for new drugs. The study of ganciclovir-resistant mutants has indicated that the selective action of ganciclovir depends largely on virus-controlled phosphorylation in HCMV-infected cells. The enzyme(s) responsible have not been identified. Here we report that the HCMV gene UL97, whose predicted product shares regions of homology with protein kinases, guanylyl cyclase and bacterial phosphotransferases, controls phosphorylation of ganciclovir in HCMV-infected cells. A four-amino-acid deletion of UL97 in a conserved region, which in cyclic AMP-dependent protein kinase participates in substrate recognition, causes impaired ganciclovir phosphorylation. The implications of these results for antiviral drug development and drug resistance are discussed.

Amino Acid Sequence↗
PubMed1992

Involvement of pertussis toxin sensitive G-proteins in conditioned fear-potentiated startle: possible involvement of the amygdala.

The present study evaluated the effects of intraventricular or intracerebral administration of pertussis toxin on fear-potentiated startle (a measure of conditioned fear) and shock sensitization (a measure of unconditioned fear). In Experiment 1 all animals were unilaterally implanted with cannulae into the lateral ventricle 1 week prior to 2 days of fear conditioning (ten light-shock pairings on each of 2 days). Five days later, animals were infused with either 1 microgram pertussis toxin or saline and tested for fear-potentiated startle 24 h after infusion and tested for shock sensitization 26 or 50 h after infusion. Pertussis toxin blocked the ability of a light conditioned stimulus to facilitate startle but did not alter the ability of acute footshock to increase startle amplitude in the same animals. In Experiment 2 bilateral infusion of 1 microgram pertussis toxin into the basolateral nuclei of the amygdala, but not the interpositus nuclei of the cerebellum, also blocked fear-potentiated startle when animals were tested 6 h after infusion. These findings suggest a role for pertussis toxin sensitive G-proteins, perhaps within the amygdala, in the expression of conditioned but not unconditioned fear.

Acoustic Stimulation↗
PubMed1992

Preliminary observations of holmium:YAG laser tissue interaction using human uterus.

Preliminary observations of a pulsed Ho:YAG laser on human uterine tissue in-vitro are presented. The tissue effect on the uterine myometrium was demonstrated using fresh uteri which had been subjected to laser energy. The laser crater and surrounding zone of thermal necrosis (ZTN) was quantified. Measurements demonstrated a consistent narrow ZTN (0.8-1.8 mm) irrespective of power or pulse frequency used. The percentage forward transmission of laser energy through 1 mm of myometrium was investigated using a pyroelectric detector and found to be 0.41%. Finally, a visible and measureable photoacoustic component to the Ho:YAG laser was demonstrated using a water bath and needle hydrophone.

Biophysical Phenomena↗
PubMed1992

The design of liposomal paramagnetic MR agents: effect of vesicle size upon the relaxivity of surface-incorporated lipophilic chelates.

The 1/T1 NMRD profiles of lipid vesicles with the paramagnetic ion Gd attached via a chelate covalently linked to the membrane surface show a peak at approximately 20 MHz indicating that fluctuations of approximately 10(-8) s contribute to the form of the dispersion profile. If the correlation time for fluctuations of the paramagnetic chelate on the membrane surface is much less than the correlation time for rotation of the lipid vesicle, it would be expected that the measured 1/T1 relaxation rate for solvent protons should be invariant with vesicle size above a certain minimum vesicle diameter. We show that this is indeed the case for vesicles in the size range 50 to 400 nm average diameter and discuss general design considerations for the preparation of vesicle-associated MR contrast agents based upon paramagnetic chelates either trapped within the vesicle interior or attached to the membrane surface.

Chelating Agents↗
PubMed1992

Immunocytochemical demonstration of T4 content and TSH-binding by cells of the thyroid of the developing chick embryo.

The numerical densities (Nv) of immunostained thyroxine (T4)-positive cells and thyrotropin-stimulating hormone (TSH)-positive cells were determined in chick embryos on Day 5.5 through Day 11.5 and Days 5.5, 7.5, 9.5, 10.5, 11.5, 12.5, 13.5, 14.5, 15.5, 16.5, and 17.5, respectively. The data demonstrate that selected cells of the "prefollicular" thyroid contain T4 and bind TSH at least as early as Day 5.5. The Nv of immunocytochemically demonstrable T4-positive cells increases gradually from Day 5.5 to Day 10.5, exhibiting a statistically significant increase (P less than 0.05) between Day 10.5 and Day 11.5. Similarly, the Nv of TSH-binding cells (Nv TSH) rises slowly from Day 5.5 until Day 11.5, followed by a statistically significant (P less than 0.05) increase between Day 11.5 and Day 12.5. The peak Nv TSH value on Day 12.5 is followed by a decline (P less than 0.05) on Day 13.5, and from Day 14.5 through Day 17.5, Nv TSH values remain relatively constant. Changes in the Nv of T4-positive and TSH-binding cells over developmental time are discussed with regard to pituitary regulation of the chick embryo thyroid and the possible contribution of the yolk to circulating T4 levels.

Animals↗
PubMed1992

Lesions of the central nucleus of the amygdala block the excitatory effects of septal ablation on the acoustic startle reflex.

Many studies have investigated the role of the septum and the amygdala in emotional behavior. While the literature is somewhat inconsistent, most studies suggest a role for the septal nuclei in the inhibition of fear and stress responses (at the behavioral, autonomic and hormonal levels) while the central nucleus of the amygdala is involved in the production of such responses. The present study examined the ability of lesions of the central nucleus of the amygdala to block the excitatory effects of complete septal ablation on the acoustic startle reflex. Septal ablation produced a significant increase in startle amplitude which was blocked by concomitant lesions of the central nucleus of the amygdala. These results suggest that the increase in startle amplitude resulting from septal damage might be due to a disinhibition of neuronal activity in the central nucleus of the amygdala, a structure known to mediate the increase in startle associated with conditioned and unconditioned fear, or from antagonistic interactions at other target sites which themselves modulate startle.

Acoustic Stimulation↗
PubMed1992

The role of the amygdala in fear-potentiated startle: implications for animal models of anxiety.

Over the past several years, major advances have been made in understanding the pharmacology of anxiety, involving three broad classes of experimental approach. One approach studies the mechanism of action of drugs that are known to treat anxiety clinically, such as the benzodiazepines. A second approach uses various animal models of fear or anxiety that are sensitive to known anxiolytic drugs, to see if they will detect new compounds. A third approach involves describing the neural pathways and neurotransmitters that are active in a state of fear or anxiety; importantly, this approach is not derived from the mechanisms of known anxiolytics. In this review, Michael Davis describes such a 'neural systems' approach to the study of fear or anxiety that uses the paradigm of fear-potentiated startle.

Amygdala↗
PubMed1992

High dose endobronchial irradiation in recurrent bronchogenic carcinoma.

Between November 1988 and March 1990, 24 patients with endobronchial tumors that had recurred after external beam radiation therapy were treated with high dose rate intraluminal irradiation. A remote afterloading high dose rate unit was used, and most patients received two endobronchial treatments, separated by a two week interval. All patients were given the same dose and dose specification to assess the feasibility and complications of the therapy. At each treatment, 15 Gy were delivered with dose specified at a radius of 6 mm from the center of the source, which corresponds to a dose of 9 Gy at a radius of 1 cm. Overall, 21 of 24 patients (88%) showed good symptomatic improvement. Of 18 patients whose chest x-ray showed evidence of collapse or atelectasis caused by tumor obstruction, 15 (83%) had evidence of reaeration. The median duration of palliation, marked by symptoms or a chest x-ray that worsened, was 26 weeks, the range varying from seven to 40 weeks. No patient died as a result of therapy and only one had a complication, bronchospasm, which responded well to bronchodilators. One patient died of hemoptysis approximately three months after treatment. Five additional patients, who were treated off protocol because they had an Eastern Cooperative Oncology Group performance status of greater than two, also received endobronchial irradiation. All five died within one month from worsening pulmonary disease, and we do not recommend endobronchial irradiation for patients with an Eastern Cooperative Oncology Group performance status of greater than two. We conclude that high dose rate endobronchial brachytherapy effectively relieves the symptoms of endobronchial obstruction due to recurrent lung cancer and can be given safely as an outpatient procedure. As the complications were minimal in this series treated with a uniform dose of 15 Gy per treatment, future studies should aim at determining the maximum tolerated dose. This technique may also be helpful as a boost after maximal external beam irradiation or to open up areas of atelectasis prior to external beam irradiation.

Adult↗
PubMed1992

N-methyl-D-aspartate lesions of the lateral and basolateral nuclei of the amygdala block fear-potentiated startle and shock sensitization of startle.

Cell bodies in the lateral and basolateral amygdaloid nuclei were destroyed by local infusion of N-methyl-D-aspartate. Adjacent areas, such as the central amygdaloid nucleus, were largely spared. Lesions were carried out before training and testing (Experiment 1) or after training but before testing (Experiment 2). In both cases, the lesions completely blocked fear-potentiated startle (increased acoustic startle in the presence of a light previously paired with footshock). They also blocked increased startle after a series of footshocks, provided they damaged the most anterior part of the basolateral nucleus. It is suggested that the lateral or basolateral amygdaloid nuclei (or both) relay visual information to the central amygdaloid nucleus, which is also critical for fear-potentiated startle. In addition, activation of the most anterior part of the basolateral nucleus may be critical for processing shock information during fear conditioning.

Amygdala↗
PubMed1992

Intra-amygdala infusion of the N-methyl-D-aspartate receptor antagonist AP5 blocks acquisition but not expression of fear-potentiated startle to an auditory conditioned stimulus.

The fear-potentiated startle paradigm, in which the amplitude of the startle reflex is enhanced in the presence of a stimulus previously paired with footshock, was used to measure aversive conditioning after intra-amygdala infusion of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5). Infusion of 2.5 micrograms/side AP5 immediately before five noise-footshock pairings on each of 2 consecutive days dose-dependently blocked acquisition or consolidation of auditory fear-potentiated startle, consistent with previous results from our laboratory obtained with a visual stimulus. Somatosensory or auditory transmission deficits do not appear to be induced by intra-amygdala AP5 because rats reacted normally to footshocks and showed reliable potentiated startle expression after pretesting AP5 infusion at a dose that blocked acquisition. Together with earlier reports, these data suggest that an NMDA-dependent process localized in or near the amygdala may be necessary for the acquisition of conditioned fear across different sensory modalities.

2-Amino-5-phosphonovalerate↗
PubMed1992

A phase I-II study of recombinant intrapleural alpha interferon in malignant pleural effusions.

Malignant pleural effusion is a common and significant source of morbidity for many patients with cancer. In an attempt to control this condition without using chest tube drainage, we administered recombinant interferon alpha-2b (INTRON, Schering-Plough, Kenilworth, NJ) intrapleurally via catheter after routine thoracentesis. Twenty-two installations of interferon were administered to 15 patients in incremental dosages of 3-50 x 10(6) U/m2. Of 20 evaluable treatments, six (30%) achieved effusion stabilization; there were no complete or partial responses. Only one of nine treatments at a dosage less than 20 x 10(6) units/m2 resulted in symptoms, while four of 11 treatments at the higher dosage were associated with transient fever, chills, and chest pain. Interferon demonstrated no major activity in this heavily treated patient population with advanced malignancy.

Adult↗