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Biomedical subjects

D A Thompson

Publications and source records attributed to D A Thompson.

At least 109 records · Page 6Linked to original sources

Genomic cloning and sequence analyses of the bovine alpha-, beta A- and beta B-inhibin/activin genes. Identification of transcription factor AP-2-binding sites in the 5'-flanking regions by DNase I footprinting.

Inhibins and activins are dimeric peptide hormones that regulate the circulating levels of follicle-stimulating hormone (FSH). In turn, FSH stimulates inhibin gene expression in the ovarian follicle; studies to date suggest that this effect is mediated by cAMP and that a cAMP-responsive element, identified in the 5'-flanking region of the alpha-inhibin gene, at least partially effects this response. To explore further the transcriptional regulation of the inhibin/activin genes, we have isolated and sequenced the 5'-flanking regions of the bovine alpha-, beta A- and beta B-inhibin/activin subunit genes and have analysed these regions by primer-extension analysis and DNase I footprinting with the transcription factor AP-2. Analyses indicated that all three gene promoter regions have a number of AP-2-binding sites that are resistant to competition by poly(dI-dC), suggesting that cAMP may control the inhibin/activin ratio by operating through alternative signal-transduction pathways or that inhibin/activin gene expression may be controlled by signals operating through the protein kinase C pathway. A comparison of the DNA sequences protected by AP-2 against DNase I digestion revealed a consensus AP-2-binding site of 5'-GSCCCDSS-3', where S represents a base pairing involving three (C or G) hydrogen bonds and D represents any base other than C. The nucleotide sequences of the bovine beta-subunit structural genes also are reported.

Activins↗

The origins of luminance and pattern responses of the pattern electroretinogram.

A luminance response is spatially insensitive and dependent upon temporal contrast. The contribution of luminance to the pattern onset electroretinogram (PERG) can be estimated from the temporal contrast of a pattern's illuminance profile on the retina. A profile can be computed for different spatial frequencies by resynthesising the Fourier transform of the pattern after it has been filtered by the eye's MTF. A pure luminance response does not fully account for the amplitude of the PERG. The residual response is called "pattern specific". After the effects of spatial contrast degradation have been corrected for the response is spatially bandpass tuned with a peak that changes with eccentricity. An optimum foveal stimulus is estimated to be 3.5' arc. The pattern specific response component shows a correlation with inner nuclear and ganglion cell volumes. When the relationship of the luminance ERG with temporal contrast was explored empirically it was found to behave in good approximation to the theoretical predictions.

Electroretinography↗

Successful resuscitation of a severely hypothermic neonate.

A profoundly hypothermic 5-hour-old infant in cardiac arrest was brought to the emergency department by paramedics. The infant was found wrapped in a garbage bag inside a freezer. She had been in the freezer for approximately four hours. Her initial rectal temperature was 16.2 degrees C. Active external and core warming modalities, including warm blanket, radiant heat lamp, warm humidified air, heated gastric lavage, and heated bladder lavage, were used to rewarm the infant. Her temperature rose to 30.5 degrees C in three hours (4.8 degrees C/hr). The infant converted from a slow idioventricular rhythm to sinus bradycardia at 49 minutes (20.4 degrees C) into the resuscitation. At 53 minutes (21.5 degrees C), the infant moved both upper extremities. At the time of discharge from the hospital, she had no significant physical or neurologic problems. Neurologic examination at 4 months was normal. This report supports prior recommendations to aggressively rewarm severely hypothermic infants in cardiac arrest.

Cardiopulmonary Resuscitation↗

Sudden rupture of an indirect inguinal hernial sac with extravasation in two patients on continuous ambulatory peritoneal dialysis.

Continuous ambulatory peritoneal dialysis (CAPD) is commonly used to treat patients suffering from end-stage renal failure. This method can be used on a long-term basis and in the short term for patients awaiting renal transplantation. Inguinal hernias are a potential source of morbidity for these patients. Therefore, when patients with inguinal hernias require long-term peritoneal dialysis, the hernia should be repaired if the patient's medical status will allow it. The authors report on two patients maintained on CAPD who experienced rapid enlargement and perforation of a previously undiagnosed asymptomatic inguinal hernia. The hernia was repaired successfully, without complication, in both cases.

Adult↗

Electromyographic power spectrum analysis of the paraspinal muscles. Long-term reliability.

As a prerequisite to the use of electromyographic power spectral analysis of the paraspinal muscles as a low-back pain treatment outcome measure, the long-term reliability of the technique was assessed. The myoelectric signals of the multifidus and iliocostalis lumborum muscles of healthy sedentary women were analyzed with regard to spectral parameters during a constant-force contraction, before and after a 3-month period. Results indicated that for both muscles, estimates of initial median frequency and amplitude had high test/retest reliability, but that the recovery and left-right difference parameters were not stable. Using a confidence interval method, test/retest variation for the fatigue parameter was found to be within the range of variability of potentially underlying metabolic processes.

Adult↗

An optical stimulator for studying the topography of electrical and magnetic visual evoked responses.

Visual processing areas cover more than 50% of the cortex in primates, but in humans only about half of this area is projected on gyral crests and thus readily accessible to investigation by evoked potential mapping. However, neuromagnetometry does not reflect the activity of these radial dipoles, but instead it strongly represents tangential dipoles, which may arise from activity within the sulci. It follows that the full exploration of the visual areas can only be achieved by combining these complementary techniques. Software-controlled video stimulators are almost universally used for evoked potential recording, but they generate troublesome interference during neural magnetometry. A simple optical stimulator was therefore designed to project a stimulus into magnetically shielded rooms from a remote situation. The system is capable of providing a wide variety of visual stimuli, including pattern reversal, onset, movement and progressive adjustment of chromatic and achromatic contrast. Evoked responses to complex images and isoluminant colored gratings were studied to demonstrate the performance of this type of system.

Color Perception↗

Pharmacologic considerations in the treatment of substance abuse.

Drug and alcohol abuse continue to be commonly encountered problems in most patient populations. To deal effectively with these problems, the primary care physician must have a thorough knowledge of the pharmacology of commonly abused drugs and the adjunctive agents used in treatment. Management of alcoholism may involve a range of medical interventions, including the treatment of alcohol intoxication, the use of benzodiazepines for alcohol withdrawal, and possibly the short-term administration of disulfiram to maintain sobriety. Successful management of cocaine or amphetamine abuse requires an understanding of the powerful reinforcing properties of these drugs and the unique problems that arise in the recovery period. Barbiturate intoxication and withdrawal are potentially life-threatening events requiring skilled in-patient treatment. Prolonged use of benzodiazepines can lead to drug dependence; successful withdrawal involves gradual dosage reduction. Acute intoxication from marijuana or hallucinogenic drugs may occasionally result in adverse reactions requiring medical intervention, but significant withdrawal reactions are rare. Management of opioid overdose, whether illicit or iatrogenic, requires the prompt and skillful use of opioid overdose, whether illicit or iatrogenic, requires the prompt and skillful use of opioid antagonists. Promising new pharmacologic approaches are now being successfully applied to the management of opioid dependence. An acceptance of nicotine as the addictive component of tobacco smoke has led to the development of nicotine gum as substitution therapy for cigarette smoking. Successful pharmacologic management of overdose or withdrawal is often the prerequisite for effective long-term treatment and recovery.

Alcoholism↗

Comparative inhibition profiles of three non-sedating antihistamines assessed by an extended Lewis model.

Antihistaminic drugs are widely prescribed across a multitude of medical specialties such as Allergy and Dermatology. The potentially serious sedative effect of these valuable agents has previously restricted their full use and the choice of drug has been dictated more by individual patient acceptability than by any laboratory demonstrations of comparative efficacy. Unsurprisingly therefore, there is a trend towards prescribing those newer preparations which leave the central nervous system unclouded. We have studied the most frequently prescribed non-sedating antihistamine preparations, terfenadine (Triludan, Triludan Forte), cetirizine (Zirtek) and loratadine (Clarityn) in pharmacodynamic and relative efficacy trials using a quantifiable and reproducible extension of the classic Lewis model. The results indicate that two preparations, terfenadine 120 mg (Triludan Forte) and cetirizine 10 mg (Zirtek) are superior to their immediate rivals in degree of efficacy and/or speed of action. These results should assist clinicians in the positioning of effective, rapidly acting antihistamines for the symptomatic treatment of immediate hypersensitivity reactions such as urticaria and rhinitis.

Adult↗

Colour, contrast and the visual evoked potential.

Visual evoked potentials exhibit interesting morphological changes when they are elicited by checkerboards of different spatial and chromatic contrast, counterphasing in the foveal and lower macula field. The characteristic, positive wave of the phase-reversal visual evoked potential, for example, is preceded by an increasingly prominent negative peak as luminance contrast progressively increases above 10% and, at isoluminance, the response to red and green checkerboards becomes a predominantly monophasic negative wave. To study the nature of the morphological change we synthesized these waveforms with a computer simulation consisting of Gaussian components. The amplitudes of positive and negative components were altered until the synthesized response was closely similar to the recorded data. These Gaussian components have response characteristics which are identified with those of magnocellular and parvocellular neurones.

Color Perception↗

Alzheimer dementia: quantification of energy metabolism and mobile phosphoesters with P-31 NMR spectroscopy.

To determine whether high-energy phosphate metabolism and mobile phosphoester indexes of membrane metabolism are altered in Alzheimer disease and to help resolve some inconsistencies in the literature, brain phosphate metabolite concentrations and ratios were measured in 11 patients with mild to severe dementia of the probable Alzheimer type and 14 healthy subjects. Fully relaxed, spatially localized, phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy and proton (hydrogen-1) MR imaging were performed. No significant differences were found in the concentrations and relative ratios of phosphocreatine, nucleoside triphosphate, inorganic phosphate, phosphomonoester, and phosphodiesters in whole axial sections through the lateral cerebral ventricles of the brain that could not be accounted for by atrophy. There was no correlation between P-31 NMR indexes and the severity of dementia as assessed with neuropsychologic testing. High-energy phosphate and membrane metabolism, as detected in vivo with P-31 NMR spectroscopy in whole-brain sections, do not appear to play a major role in the disease process, except as a direct consequence of atrophy quantified with H-1 MR imaging.

Aged↗

Electroretinography as a prognostic indicator or neovascularisation in CRVO.

A prospective study was carried out to compare the efficacy of electroretinography, fundus fluorescein angiography and clinical examination in identifying those at risk of rubeotic glaucoma following central retinal vein occlusion (CRVO). Our preliminary observations are described. The findings suggest a complementary role for electroretinography in the management of CRVO. Particularly significant were interocular differences in 30 Hz flicker latency, the ability to elicit pattern ERGs and the ratio of scotopic and photopic a:b wave amplitudes. Of the clinical measures the depth of the relative afferent pupil defect was a sensitive indicator of rubeosis. Factors of lesser statistical prognostic value included poor visual acuity and the extent of deep retinal haemorrhages. Fundus fluorescein angiography in this study had limited value in predicting those patients at risk of rubeosis.

Electroretinography↗

A transforming growth factor beta 2 (TGF-beta 2)-like immunosuppressive factor in amniotic fluid and localization of TGF-beta 2 mRNA in the pregnant uterus.

This report describes a murine amniotic fluid (MAF) immunosuppressive factor that has properties similar to transforming growth factor beta (TGF-beta). The MAF factor exhibits TGF-beta-like activity in stimulating soft agar colony formation by AKR-2B cells and inhibiting thymidine uptake by Mv1Lu cells. We demonstrate that both the immunosuppressive and TGF-beta-like activities of the MAF factor are completely neutralized by anti-TGF-beta 2-specific antibodies and not by anti-TGF-beta 1-specific antisera. The immunosuppressive factor in MAF is novel in that it appears to be identical or very closely related to TGF-beta 2 and is active in its native state. This active and anti-TGF-beta 2-neutralizable factor chromatographs at approximately 70 kD on Sephadex at neutral pH and appears to be able to complex with alpha-fetoprotein in native amniotic fluid. Chromatography of native MAF under acidic conditions demonstrates a lower molecular mass protein that chromatographs on BioGel in the same position as the mature 25-kD TGF-beta. This protein has the biological properties of TGF-beta and is immunosuppressive. Both of these activities are neutralizable with anti-TGF-beta 2 but not with anti-TGF-beta 1 or other antisera. By Northern analysis, we find high levels of TGF-beta 2 mRNA (with little or no TGF-beta 1) in the pregnant uterus that peak around day 15 of gestation and then fall rapidly by day 19 as birth approaches. The TGF-beta 2-like factor could possibly play a role in maternal immunity, in the retention of the fetal allograft, as well as in regulating fetal and neonatal immunological competence.

Amniotic Fluid↗

Guanosine 3',5'-cyclic nucleotide binding proteins of bovine retina identified by photoaffinity labeling.

Cyclic GMP-binding proteins present in membrane fractions of bovine retina and, in particular, rod outer segments (ROS) were identified by photoaffinity labeling with 8-azido-[32P]cGMP. Two soluble proteins and two membrane-associated proteins were specifically labeled. The soluble proteins, 93 and 72 kDa, corresponded respectively to the alpha subunit of ROS cGMP phosphodiesterase and cGMP-dependent protein kinase. One of the two membrane-associated proteins, 53 kDa, was present in all particulate retinal fractions. Its function is unknown. It is distinct from cAMP-dependent protein kinase or the 63-kDa cGMP-activated channel from ROS. The second membrane-associated protein, 37 kDa, was present only in fractions that did not contain ROS. The molecular mass of this protein was similar to that of a cGMP-binding protein previously attributed to rod cells.

Affinity Labels↗

Evidence that receptors controlling growth hormone and hyperglycemic responses to glucoprivation are located in the hindbrain.

Infusions of the glucose analogue 5-thioglucose (5TG) were performed either in the lateral or fourth ventricle in animals having a patent or blocked cerebral aqueduct in order to determine the location of glucoreceptor(s) responsible for the hyperglycemic and growth hormone (rGH) responses to glucoprivation. Infusion of 5TG in the fourth ventricle induced hyperglycemia and a decrease in rGH levels whether or not the aqueduct was patent. Infusion of 5TG in the lateral ventricle produced the hyperglycemic response without decreasing rGH in animals with the aqueduct patent whereas both responses were abolished in animals with the aqueduct blocked. These results indicate that glucoreceptors that mediate hyperglycemia and a decrease in rGH in response to cerebral glucoprivation are located in the hindbrain.

Animals↗

Cytochrome P450IIIA enzymes in rat liver microsomes: involvement in C3-hydroxylation of diazepam and nordazepam but not N-dealkylation of diazepam and temazepam.

Microsomes prepared from livers of male and female rats of nine inbred and outbred strains and of male Sprague-Dawley rats pretreated with monooxygenase-inducing agents were used to study N-dealkylation of diazepam and temazepam and C3-hydroxylation of diazepam and nordazepam. Both C3-hydroxylation reactions were more rapid in male than in female liver preparations, but this gender-dependent pattern was not seen with the N-dealkylation reactions. These results indicate the lack of identity of the monooxygenases responsible for the two kinds of reaction and suggest that male-specific enzyme(s) are responsible for the C3-hydroxylations. Induction studies were undertaken to further define these enzymes. To do this, liver microsomes prepared from male Sprague-Dawley rats pretreated with a variety of agents known to have different monooxygenase induction effects were used. With triacetyloleandomycin, dexamethasone, and phenobarbital pretreatment, the specific activities of the C3-hydroxylation reactions were selectively elevated over corresponding control values. These particular xenobiotics are known to enhance the abundance of cytochrome P450IIIA family enzymes, and our results strongly suggest the involvement of these enzymes in the benzodiazepine B ring monooxygenations. Formation of temazepam was also shown to be inhibited by triacetyloleandomycin. This effect was demonstrated to be equal in both saline-treated and dexamethasone-treated male Sprague-Dawley rat liver microsomes, with the antibiotic present either with diazepam throughout the entire incubation period or initially with NADPH in a preincubation mix for 15 min, following which C3-hydroxylation was initiated by the addition of diazepam. These results confirm the uniformity of the involvement of cytochrome P450IIIA family enzymes in diazepam C3-hydroxylation in untreated and inducer-treated rat liver microsomes. Recent studies with human and rabbit liver microsomal preparations have shown that orthologues of these enzymes also catalyze an equivalent hydroxylation in the B ring of midazolam. These findings, considered with the present results showing that the adjacent methyl N-substituent (absent in nordazepam but present in diazepam) did not affect the selectivity of these enzymes for the C3-hydroxylation reaction, suggest that neither steric nor electronic factors markedly influence catalysis of this monooxygenation by these enzymes.

Animals↗

Effects of method of hemostasis on wound-infection rate.

Adequate hemostasis is important in preventing postoperative wound infection. This study compared four methods of hemostasis: specific pinpoint vessel electrocautery (SPC), specific vessel ligation with 4-0 vicryl (SVL), nonspecific electrocautery of vessel plus excessive surrounding tissue (NSC), and nonspecific ligation of vessel and excessive surrounding tissue with 4-0 vicryl (NSL), on the rate of wound infection in rabbits that were contaminated with 10(6) Staphylococcus aureus. There was no statistical significant increase in the rate of wound sepsis when electrocautery was used in a fashion producing minimal nonviable tissue compared to specific vessel ligation. Electrocautery use for specific vessel hemostasis does not result in a higher wound infection rate in contaminated wounds.

Animals↗