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Biomedical subjects

M Moore

Publications and source records attributed to M Moore.

At least 361 records · Page 20Linked to original sources

The adenovirus E1B-55K transforming polypeptide modulates transport or cytoplasmic stabilization of viral and host cell mRNAs.

The adenovirus type 5 mutant H5dl338 lacks 524 base pairs within early region 1B. The mutation removed a portion of the region encoding the related E1B-55K and -17K polypeptides but did not disturb the E1B-21K coding region. The virus can be propagated in 293 cells which contain and express the adenovirus type 5 E1A and E1B regions, but it is defective for growth in HeLa cells, in which its final yield is reduced about 100-fold compared with the wild-type virus. The mutant also fails to transform rat cells at normal efficiency. The site of the dl338 defect was studied in HeLa cells. Early gene expression and DNA replication appeared normal. Late after infection, mRNAs coded by the major late transcription unit accumulated to reduced levels. At a time when transcription rates and steady-state nuclear RNA species were normal, the rate at which late mRNA accumulated in the cytoplasm was markedly reduced. Furthermore, in contrast to the case with the wild type, transport and accumulation of cellular mRNAs continued late after infection with dl338. Thus, the E1B product appears to facilitate transport and accumulation of viral mRNAs late after infection while blocking the same processes for cellular mRNAs.

Adenovirus Early Proteins↗

Immunohistochemical detection of ras oncogene p21 product in benign and malignant mammary tissue in man.

The monoclonal antibody RAP-5 generated against a synthetic peptide corresponding to amino acid positions 10-17 of the ras p21 protein was used in an immunohistochemical study of the expression of ras in normal, benign, and malignant breast epithelium in man. The staining intensity and intracellular distribution of RAP-5 was similar in the three epithelial populations and extended to other tissue elements including myoepithelial cells, smooth muscle, myelin, capillary endothelium, and stromal fibroblasts, as well as sebaceous glands and sweat glands overlying the breast. These results suggest that RAP-5 recognises a normal cellular component, the expression of which is not more enhanced in hyperplastic or neoplastic conditions. The detection of mutant forms of p21 exclusively expressed in malignant tumours requires that alternative reagents be developed.

Adenofibroma↗

Increased phenylalanine incorporation in regenerating skeletal muscle grafts.

Skeletal muscle regenerates following grafting, but little is known about protein synthesis and its regulation during regeneration. We determined the sequence of changes in protein synthesis in rat extensor digitorum longus (EDL) muscle by the measurement of phenylalanine (Phe) incorporation into muscle protein at various times after grafting. Compared with control EDL, Phe incorporation in grafts doubled in 1 day, was four- to eight-fold greater from days 2 to 10 after grafting, and then subsided. Tissue mass (wet weight) increased rapidly from days 7 to 20 in EDL grafts. The maximal increase in protein synthesis occurred 7-10 days after grafting, whether or not the nerve was left intact. Autoradiography indicated that incorporated radioactivity was associated with regenerating muscle fibers on day 10. Deficiencies of insulin, pituitary or testicular hormones, or chronic in vivo administration of insulin, growth hormone, testosterone, or tri-iodothyronine did not substantially alter the elevation in incorporation of the Phe into muscle protein 10 days after grafting. The breakdown of EDL protein, measured in vitro simultaneously with protein synthesis, was increased five-fold, and overall protein degradation was elevated six-fold 10 days after grafting. These findings indicate that Phe incorporation is rapidly elevated following grafting of the EDL, and that by days 7-10 reflects synthesis in regenerating muscle fibers. The increase in protein synthesis associated with muscle regeneration at this time appears to be independent of innervation and anabolic hormones.

Animals↗

Fetal breathing and behavior measured through a double-wall Plexiglas window in sheep.

The inability to see the fetus makes the assessment of fetal behavior difficult. To circumvent this problem we implanted a Plexiglas window in the left flank of the ewe. Fetuses were instrumented for measurements of sleep, breathing, and swallowing. Ten fetal sheep were studied on 32 occasions. Six fetuses were delivered through the window at term, and postnatal behavior was compared with intrauterine behavior. Fetuses observed during resting conditions alternated between periods of quiet sleep [high-voltage electrocortical activity (ECoG)] and active or rapid-eye-movement sleep (low-voltage ECoG). In quiet sleep, movements were absent except for periodic generalized electromyographic discharges. Eye and breathing movements were rare or absent. Swallowing was also absent. In active sleep, movements were increased with powerful breathing and swallowing activity. Fetal wakefulness defined by open eyes and purposeful movements of the head was never seen in utero but was clearly observed after delivery. We conclude that fetal wakefulness as defined postnatally was not able to be demonstrated in utero.

Animals↗

Intravenous omeprazole: effect on 24-hour intragastric pH in duodenal ulcer patients.

This study was aimed to identify an intravenous dosage regime of omeprazole which would sufficiently suppress acid secretion to maintain intragastric pH greater than 4 continuously. Thirteen duodenal ulcer patients in remission received omeprazole in daily intravenous doses ranging from 40 to 200 mg. Doses were successively increased as dictated by patient response. The intragastric pH data indicated that omeprazole given in twice or thrice daily regimes in total intravenous amounts of 200, 160 and 160 mg over a consecutive 3-day period markedly inhibited acid secretion and maintained intragastric pH greater than 4 with few and short-term exceptions.

Adult↗

Ontogenic development of gastrointestinal motility: IV. Duodenal contractions in preterm infants.

Duodenal motility was studied by intraluminal manometry in 27 healthy infants of 26 to 42 weeks, gestational age. The frequency of contractions, the number of contractions per burst, and the intraluminal peak pressure during contractions all increased during a narrow postconceptual period, 29 to 32 weeks, regardless of length of gestation before birth. Antenatal beta-methasone administration to the mothers of 11 additional infants of 26 to 32 weeks gestational age was associated with increased duodenal contraction rate, number of contractions per burst, and intraluminal peak pressure compared with infants of similar gestational age whose mothers did not receive beta-methasone. The maturational effect of beta-methasone on duodenal motility was most pronounced in infants whose gestational age at birth was 26 to 29 weeks. Seven infants of 31 weeks' or longer gestational duration who had a CNS abnormality or insult had fasting duodenal contraction rates that were less than one half of the rate for normal infants of similar gestational age. These observations suggest that neonatal duodenal motility undergoes marked maturational changes between 29 and 32 weeks after conception and that these changes may be inducible before 29 weeks by corticosteroid administration. An intact CNS appears to be required for full expression of the maturational changes.

Betamethasone↗

Studies of the effect of 1,25-dihydroxycholecalciferol on the proliferation and differentiation of the human promyelocytic leukaemia cell line HL-60.

Treatment of the human promyelocytic leukaemia cell line HL-60 with 1,25(OH)2D3, the active metabolite of vitamin D3, led to a dose- and time-dependent inhibition of growth and 3H-TdR incorporation at the population level. A similar effect was noted at the single cell level in clonogenic assays and autoradiographic experiments. Flow cytometry indicated that there was an arrest of cells in the G0/G1 phase of the cell cycle. Parallel to the loss of proliferative capacity 1,25(OH)2D3 induced differentiation of HL-60 into monocyte/macrophages as measured by the enzyme NSE and the macrophage membrane antigen recognised by the monoclonal antibody EB11 as well as by morphological changes. These findings reinforce the concept of concordant induction of differentiation and loss of proliferative capacity and demonstrate that the latter occurs not only at the population level but also at the single cell level in this system. In limiting dilution assays in liquid culture there was evidence for positive interactions between HL-60 cells as untreated cells gave less colonies at low dilutions than would have been expected by Poisson statistical analysis. In the presence of 10(-8) M 1,25(OH)2D3 more complex growth parameters were noted indicating the involvement of both positive and negative cellular interactions.

Calcitriol↗

Presentation of a soluble bacterial antigen and cell-surface alloantigens by large granular lymphocytes (LGL) in comparison with monocytes.

The ability of large granular lymphocytes (LGL) to function as antigen-presenting cells (APC) in the proliferative response to the soluble bacterial antigen streptolysin O (SLO) was investigated. Despite the fact that a subset of LGL isolated by sorting peripheral blood lymphocytes with the B73.1 monoclonal antibody on a fluorescence-activated cell sorter (FACS-IV) expressed MHC Class II molecules of the DP, DQ and DR subregion loci, presentation of SLO by LGL was not demonstrated. Thus, T-cell populations containing LGL but carefully depleted of monocytes, isolated either by sorting using the FACS-IV or by SRBC-rosetting, were unresponsive to antigenic stimulation with SLO. Application of exogenous interleukin-1 to FACS-IV-isolated LGL-containing T-cell populations did not elicit presentation of SLO by the LGL. In vitro activation with phytohaemagglutinin and interleukin-2, which induced Class II expression in T-cell populations, resulted in an increased expression of Class II molecules of the DP, DQ and DR specificities on LGL. Although such activated T-cell and LGL populations were incapable of presenting SLO to freshly isolated antigen-non-responsive T cells, both activated populations were able to act as stimulators in an allogeneic mixed lymphocyte reaction. The ability of highly Class II-positive activated LGL to present membrane-bound antigens suggests that their inability to present a soluble antigen may be related to the absence of effective antigen sequestration and/or processing mechanisms.

Antigen-Presenting Cells↗

The relative potencies of thiopentone and propofol.

The relative potencies of the intravenous anaesthetics propofol and thiopentone have been investigated by finding the dose necessary to produce unconsciousness in approximately 30%, 50% and 80% of patients. The estimated potency of propofol to thiopentone was 1:1.604 as obtained by the probit method of analysis which estimates the logarithm of the relative potency.

Adolescent↗

Thoracic outlet syndrome experience in a metropolitan hospital.

This clinical review emphasizes the need for cooperative management of the syndrome by the diverse and various treating disciplines. Trauma is now recognized as a much more frequent cause for persistence of the syndrome than had been previously appreciated. Reoperation in failed cases that were persistently nonresponsive to all other therapy usually shows a clear basis for symptoms such as adherence of vessels to first rib, marked local scarring and/or vascular stenosis, as well as nerve trunk adhesions. Nonoperative care is still the first choice for primary treatment. Any of the surgical disciplines can and should care for such patients so long as the surgeon is capable of performing any and all surgical procedures needed.

Adult↗

Standing out from the crowd: personalization of graduation attire.

During 1982 and 1983 college commencement ceremonies, a tally was made of students who displayed personal adornment in addition to their traditional academic garb. Degree conferred, sex of recipient, and year of graduation were related to the frequency and forms (political and nonpolitical) of adornment. Bachelor of Arts candidates were more likely to be adorned than were Bachelor of Science candidates, women were more likely to be adorned than were men, and 1982 graduates were more likely to be adorned than were 1983 graduates. The wearing of antinuclear protest ribbons varied as a function of degree but not as a function of sex, and the wearing of nonpolitical forms of adornment varied as a function of sex but not as a function of degree. Results indicate that personalization of graduation attire follows patterns reported in studies of secular dress and adornment. This correspondence between everyday and ritual clothing expressions suggests that the graduation ceremony may be a useful microcosm for future field studies of adolescents' attitudes and social differentiation.

Adolescent↗

Systemic sclerosis and pregnancy complicated by obstructive uropathy.

A patient with progressive systemic sclerosis whose twin pregnancy was complicated by obstructive uropathy due, in part, to a noncompliant abdominal wall is reported. The effects of progressive systemic sclerosis on pregnancy and those of pregnancy on progressive systemic sclerosis are reviewed and discussed.

Abdominal Muscles↗

The toxicity of acetaminophen and N-acetyl-p-benzoquinone imine in isolated hepatocytes is associated with thiol depletion and increased cytosolic Ca2+.

The effects of acetaminophen and its major toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), have been investigated in hepatocytes isolated from 3-methylcholanthrene-pretreated and -untreated rats, respectively. The two compounds produced qualitatively similar changes although the quinone imine was toxic with shorter incubations periods and at lower doses. Both agents caused an elevation of cytosolic Ca2+, assessed by phosphorylase a activity, which was accompanied by the concomitant appearance of plasma membrane blebs. A loss of mitochondrial Ca2+ was also observed. This disruption of Ca2+ homeostasis always preceded cell death. Studies with NAPQI showed that low doses were able to cause complete Ca2+ release from isolated liver mitochondria which was accompanied by pyridine nucleotide oxidation and preceded membrane damage. NAPQI also produced a rapid, dose-dependent depletion of both cytosolic and mitochondrial reduced glutathione as well as a loss of protein-bound SH groups. This loss of protein thiols may have been responsible for the observed inhibition of the high-affinity Ca2+-ATPase activity of the plasma membrane fraction isolated from NAPQI-treated cells. In addition, NAPQI inhibited microsomal Ca2+ uptake which would further contribute to the elevation in cytosolic Ca2+. Our results suggest that acetaminophen and N-acetyl-p-benzoquinone imine exert their cytotoxic effects via a disruption of Ca2+ homeostasis secondary to the depletion of soluble and protein-bound thiols. This mechanism may prove to be of general applicability to a variety of hepatotoxins.

Acetaminophen↗

Demonstration and partial characterization of glutathione disulfide-stimulated ATPase activity in the plasma membrane fraction from rat hepatocytes.

A highly purified plasma membrane fraction isolated from rat hepatocytes was found to catalyze the hydrolysis of ATP in response to micromolar concentrations of glutathione disulfide (GSSG). This process exhibited distinct kinetic parameters suggesting the existence of both a high and low affinity component. The apparent Km values (GSSG) for ATP hydrolysis were 140 microM and 1 mM for the high affinity and low affinity components, respectively. Disulfides other than GSSG were also found to stimulate ATP hydrolysis. The similarity between the kinetic properties of the GSSG-stimulated ATPase and those reported for GSSG transport in erythrocytes (Kondo, T., Dale, G. L., and Beutler, E. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 6359-6362) suggests that the ATPase may function in the active extrusion of intracellular GSSG.

Adenosine Triphosphatases↗

Pseudomonas dermatitis associated with a swimming pool.

One hundred forty-seven (66%) of 224 scouts and chaperons were interviewed after a weekend visit to a dude ranch in upstate New York. One hundred seventeen (80%) complained of papular rashes or eye and ear inflammation. Onset of illness occurred within 24 to 48 hours of arrival at the ranch. After controlling for participation in other available activities, only swimming was found to be associated with illness. Pseudomonas aeruginosa serotype 0 11 grew from a culture of pool water and from 17 cultures of skin, eye, and ear lesions in visitors to the ranch. Follow-up was obtained for 76 of the affected persons for whom initial information was available. Mean duration of illness was 14.5 days (range, one to 40+ days). The recurrence rate was 24%.

Adult↗