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Biomedical subjects

P Thompson

Publications and source records attributed to P Thompson.

At least 181 records · Page 10Linked to original sources

Dexamethasone and pentoxifylline inhibit endotoxin-induced cachectin/tumor necrosis factor synthesis at separate points in the signaling pathway.

The induction of cachectin/tumor necrosis factor (TNF) synthesis by bacterial endotoxins is a process that entails activation at several levels. Cachectin/TNF gene transcription is accelerated, leading to rapid accumulation of mRNA within the macrophage cytosol. In addition, translational derepression occurs, leading to far more efficient message utilization. Through the use of posttranscriptional reporter constructs, we now demonstrate that certain agents capable of inhibiting cachectin/TNF biosynthesis operate through different mechanisms. In RAW 264.7 macrophages, pentoxifylline blocks cachectin/TNF mRNA accumulation but has no effect upon the efficiency of reporter mRNA translation. Dexamethasone, on the other hand, has only a modest effect on cachectin/TNF mRNA accumulation, but strongly impedes translational derepression. Combined application of dexamethasone and pentoxifylline to macrophages causes a greater suppression of cachectin/TNF biosynthesis that can be achieved by either agent alone. These findings suggest that the signaling pathway activated by endotoxin is branched, and that selective inhibition of different parts of the pathway may be achieved through the use of distinct agents.

Animals↗

Preparation of fluorescently labelled hybrid histone octamers.

Labelling hybrid histone octamers (the Cys variant of histone H4 replaced histone H4 in the chicken erythrocyte octamer) with the fluorescent probe 5-(2(iodoacetyl)aminoethyl)aminonapthalene- 1-sulfonic acid, IAEDANS, resulted in significant non-specific incorporation of label. Fluorescently labelled hybrid histone octamers were prepared by reconstitution methodology after labelling the isolated histone Cys-H4 and separation of specifically and non-specifically labelled histone. Core particles prepared from these octamers have identical thermal denaturation to unlabelled core particles demonstrating that the incorporation of a fluorescent probe at this site has no overall effect on either histone-histone or histone-DNA interactions. DNase 1 digestion of 32P end-labelled fluorescent core particles yielded the anticipated asymmetric cutting pattern with a 10 bp interval between fragments. Comparison of the cutting pattern with those previously obtained in these laboratories for both polyglutamic acid reconstituted and 'native' core particles demonstrated that fluorescent core particles had an enhanced susceptibility to digestion at site 7.

Amino Acids↗

The genetics of a small autosomal region of Drosophila melanogaster containing the structural gene for alcohol dehydrogenase. VII. Characterization of the region around the snail and cactus loci.

The genetic interval 35C to 36A on chromosome arm 2L of Drosophila melanogaster has been saturated for mutations with visible or lethal phenotypes. 38 loci have been characterized, including several maternal-effect lethals (vasa, Bic-C, chiffon, cactus and cornichon) and several early embryonic lethals, including snail and fizzy. About 130 deletions have been used to order these loci. Complex interactions between mutant alleles have been uncovered in the immediate genetic environs of the snail gene, as has further evidence for an interaction between this region and that including the nearby genes no-ocelli and elbow.

Alcohol Dehydrogenase↗

Relationship between enteric migrating motor complex and the sleep cycle.

To address the question of synchrony between two major biorhythms with a similar periodicity, the cortical rapid eye movement (REM)/non-REM sleep cycle and the enteric migrating motor complex (MMC cycle), we recorded upper small bowel motor activity and sleep activity during nocturnal and diurnal sleep in six healthy subjects. Motility was measured continuously using a fine (2.2 mm OD) and relatively comfortable nasojejunal probe with two pressure-sensitive microtransducers positioned under fluoroscopic control on either side of the ligament of Treitz. Sleep stages were recorded while the subjects slept in a sleep laboratory. Each subject was studied twice; once during normal nocturnal sleep and then after acute reversal of sleep by advancing the time of going to bed by 4 h each night for three nights. The total duration of sleep was similar for diurnal and nocturnal sleep. There was a significantly higher number of REM episodes (P less than 0.001) and REM sleep stage shifts (P less than 0.02) during diurnal (reversed) sleep. During sleep (both diurnal and nocturnal) there was a significant reduction in the MMC cycle length (P less than 0.02, P less than 0.03) and the duration of phase II of the MMC (P less than 0.009, P less than 0.02). The distribution of MMCs among sleep stages and REM sleep was consistent with a random distribution. These data show that periodic activity in the gut is modulated by the presence or absence of sleep, but they also are consistent with the hypothesis that the two cycles are independent and that one is not contingent upon the other.

Adult↗

Planning the move of patient activities at a large medical center.

The planning for the move of inpatients and outpatients to a new 845-bed, 1.5 million square foot facility that took place over a period of two and one-half years and encompassed the health care, safety, and social needs of both inpatients and outpatients and their families is described. The length of time given to the planning process allowed the hospital personnel to undertake planning the move along with their regular duties and without the need for additional staff, plus allowed for very detailed planning. The precise estimate of time requirements for the inpatient move resulted in the move being completed within two minutes of the projected 150-minute estimate. Moving patients from one health care facility to another can be accomplished safely and efficiently with the aid of a well-developed plan and sufficient practice of all needed functions.

Forms and Records Control↗

Isolation and characterisation of a 167 bp core particle isolated from stripped chicken erythrocyte chromatin.

We have digested chicken erythrocyte soluble chromatin, both unstripped and stripped of histones H1 and H5 with either 0.6 M NaCl or DNA-cellulose, with micrococcal nuclease (MNase). Digestion of unstripped chromatin to monomeric particles initially paused at 188 bp DNA; continued digestion resulted in another pause at 177 before the 167 bp chromatosome and 146 bp core particle were obtained. Digestion of stripped chromatin to monomeric particles paused transiently at 177 bp; continued digestion resulted in marked pauses at 167 and 156 before the 146 bp core particle was obtained. These results suggested that 167 bp DNA representing two complete turns are bound to the histone octamer. Histone H1/H5 binds an additional two helical turns of DNA, thereby protecting up to 188 bp DNA against nuclease digestion. Monomeric particles containing 167 bp DNA were isolated from stripped chromatin and found by DNase I digestion to be a homogeneous population with a 10 bp DNA extension to either end relative to the 146 bp core particle. Thermal denaturation and circular dichroism spectroscopy showed stronger histone-DNA interactions and increased DNA winding as the length of DNA attached to the core histone octamer was decreased. Thermal denaturation also showed three classes of histone-DNA interaction: the core particle containing 167 bp DNA had tight binding of ten helical turns of DNA, intermediate binding of two helical turns and looser binding of four helical turns.

Animals↗

Making Mayhew and Frisby effortlessly discriminable.

Mayhew and Frisby (1978) demonstrated that patterns which differ markedly in their spatial-frequency content may be very hard to discriminate. This they took as evidence against any model which proposes that the processes underlying texture discrimination have direct access to some local piecewise Fourier analysis of the patterns performed by spatial-frequency channels. It is shown that Mayhew and Frisby's patterns can be discriminated easily if their components have been incorporated into a pattern-contingent colour aftereffect. This demonstration suggests that the location in the visual pathway for contingent aftereffect adaptation must lie before the construction of the raw primal sketch, to which, according to Marr, we have conscious access. This location must also allow the orientation specificity seen in the aftereffect. This points to a locus in the striate cortex.

Adult↗

Spatiotemporal contrast sensitivity and colour vision in multiple sclerosis.

Measures of contrast sensitivity and colour vision were taken from a group of 18 multiple sclerosis patients. Contrast sensitivity losses, measured at 5 spatial frequencies and 4 temporal frequencies, were found to be significant in 11 patients. Red/green (Rayleigh equation) and green/blue (Engelking-Trendelenburg equation) Pickford-Nicolson anomaloscope settings were abnormal in 15 patients. Correlating each of the 20 spatiotemporal losses with the colour losses revealed that in 19 conditions the red/green loss was greater than the green/blue loss. None of the green/blue losses correlated significantly with spatiotemporal losses while between 2 and 8 cycles/deg 11/12 spatiotemporal conditions showed significant correlations with red/green colour loss. These results support a locus of damage before the cortex at a stage in the visual pathway where red/green chromatic information may be encoded in pathways which also code luminance information.

Adult↗

The treatment of severe action myoclonus.

Ten patients with severe disabling myoclonus were treated with clonazepam, sodium valproate, primidone and piracetam alone, or in different combinations. Electrophysiological assessment indicated a cortical origin for the myoclonus in every case. Considerable improvement of myoclonus was achieved with combinations of these drugs in all patients, but this was not possible with monotherapy. In one patient two drugs were necessary (clonazepam and piracetam); in the others more than two drugs were required. The combination of sodium valproate, clonazepam and primidone (3 patients), or piracetam, clonazepam and primidone (3 patients), or the four drugs together (3 patients) was necessary to provide substantial relief of myoclonus. Such polytherapy generally was tolerated well. The benefits of treatment continued for more than 1 year in all cases, although progressive underlying pathology often caused other increasing disability.

Adolescent↗

Changes in cardiac output after acute blood loss and position change in man.

Thoracic bioimpedance cardiac output (Qtbi) was measured at 1-min intervals in 27 volunteers before, during, and after withdrawing 500 ml (3.7 to 8.5 ml/kg; mean 5.8) of blood. The effects of passive leg raising (PLR) and standing on Qtbi were measured before and after blood withdrawal. Arterial oxygen saturation (SaO2), transcutaneous oxygen tension (PtcO2), mean arterial BP (MAP), and heart rate (HR) were also measured before and after blood withdrawal. Thoracic bioimpedance cardiac index (CI) decreased 18% (0.8 +/- 0.1 L/min.m2, p less than .0001) and stroke volume index (SI) decreased 22% (14.8 +/- 2.7 ml/beat.m2, p less than .0001) after blood withdrawal. HR, MAP, SaO2, and PtcO2 were not significantly different after blood withdrawal. Before blood withdrawal PLR increased CI 6.8% (0.3 +/- 0.1 L/min.m2, p less than .0001); after blood withdrawal PLR increased CI 11.1% (0.4 +/- 0.1 L/min.m2, p less than .0001). PLR can increase stroke volume and cardiac output in hypovolemic humans.

Acute Disease↗

Tuberculous epididymo-orchitis: clinical and ultrasound observations.

The clinical, radiological and ultrasound features of 3 patients presenting with tuberculous epididymo-orchitis are described and the relevant literature reviewed. Scrotal swelling, pain and sinuses are common features at presentation. The presence of a sterile pyuria is a useful sign, but intravenous urography may fail to identify active renal disease. Ultrasound examination revealed testicular involvement in 2 patients. Differentiation from tumour may not be possible, but the presence of epididymal involvement strongly suggests an infective cause. Early surgical biopsy may prove helpful if acid-fast bacilli are not initially identified in early morning urine samples.

Adult↗

Primary lymphoma of the liver in a patient with acquired immune deficiency syndrome and chronic hepatitis B.

We describe the case of a homosexual man with asymptomatic infection with human immunodeficiency virus and hepatitis B virus who developed primary hepatic lymphoma. The lymphoma presented with rapid enlargement of the liver, and ultrasound examination revealed multiple hypoechoic lesions within the liver. Histological examination of the liver showed massive replacement by lymphomatous tissue, as well as changes of chronic active hepatitis B. Immunohistochemical stains for hepatitis B surface and core antigens were strongly positive in almost all hepatocytes, but not in tumor tissue. Whereas the occurrence of lymphoma probably is related to HIV infection, possible interactions between hepatitis B virus and HIV infection are discussed. Thus, the presence of mass lesions within the liver in a patient with HIV infection should raise the possibility of hepatic lymphoma even if there is no evidence of generalized lymphadenopathy.

Acquired Immunodeficiency Syndrome↗

Percutaneous transthoracic needle aspiration lung biopsy in the community hospital.

In 108 cases in which transthoracic needle aspiration biopsies were studied at Raleigh General Hospital in Beckley, West Virginia, from 1983 through 1987, the pathologic diagnoses were compared and correlated with the subsequent clinical course. The procedure was performed under C.T. guidance. Correlation of pathology with the clinical course yielded 67 per cent (72 cases) true positives, 19 per cent (20 cases) true negatives, four per cent (four cases) false negatives, zero per cent (zero cases) false positives, and 11 per cent (12 cases) indeterminates. In 23 per cent of the cases, there were radiologically demonstrated pneumothoraces, with placement of a chest tube required in 12 per cent of the cases. Hemoptysis occurred in eight per cent of the patients. The results confirmed the appropriateness of using transthoracic needle aspiration biopsies at this hospital.

Biopsy, Needle↗

Fura-2 used as a probe to show elevated intracellular free calcium in platelets of Dahl-sensitive rats fed a high salt diet.

Elevated intracellular free calcium concentration [Ca2+]i in vascular smooth muscle cells has been implicated in the pathophysiology of hypertension. Platelet [Ca2+]i was measured using the fluorescent indicator, Fura-2, in Dahl sensitive (DS) and resistant (DR) rats given high (8% NaCl) and low (0.4% NaCl) salt diets, as well as in the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. The aim of this study was to show whether [Ca2+]i is elevated in salt induced hypertension. Platelet [Ca2+]i and systolic blood pressure (SBP) were higher (p less than 0.001) in DS rats given a high than low salt diets. In contrast, no changes in platelet [Ca2+]i and SBP were observed in DR rats. In SHR, platelet [Ca2+]i and SBP were higher (p less than 0.001) than in the WKY rats. Platelet [Ca2+]i correlated with SBP in all groups of rats (r = 0.929; p less than 0.001, n = 38). The parallel increase in SBP and [Ca2+]i in the DS high salt rats and the SHR suggests that an increased [Ca2+]i is involved in the pathophysiology of hypertension in the two models which differ with respect to the pathogenesis of their hypertension. This increase in [Ca2+]i therefore seems to reflect an abnormality in [Ca2+]i handling in hypertension regardless of its cause.

Animals↗

Assay of a ribonuclease that preferentially hydrolyses mRNAs containing cytokine-derived UA-rich instability sequences.

mRNA molecules encoding a number of inflammatory cytokines, as well as certain proto-oncogenes, contain a conserved UA-exclusive sequence in the 3' untranslated region that confers message instability in vivo. This sequence may comprise a critical regulatory element, governing the level of these mRNA molecules, and determining the efficiency with which they are translated. Through the use of a double-label RNAse assay, we have determined that lysates prepared from mouse macrophages selectively degrade mRNA molecules containing the 3' untranslated UA sequence found in the mRNA encoding human cachectin/TNF. The degree of instability is dependent upon the number of copies of inserted UA sequence present in the target mRNA molecule (a Xenopus beta-globin mRNA). mRNAs containing randomly generated UA sequences are more labile than unmodified globin mRNA, but less susceptible to degradation than mRNAs containing the authentic cachectin-derived sequence. mRNA molecules containing synthetic UG-exclusive sequences are normally stable or protected in vitro. The destruction of UA-containing mRNA is inhibited by random adenylate/uridilate copolymers, but not by guanylate/uridilate copolymers. Boiling or proteinase K treatment destroys the selective nucleolytic activity of macrophage lysates. We propose that the nuclease measured here may serve to regulate cellular levels of mRNA molecules encoding cachectin, other inflammatory cytokines, and certain proto-oncogene products.

Adenine↗