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Biomedical subjects

P Moore

Publications and source records attributed to P Moore.

At least 217 records · Page 12Linked to original sources

Serum free thyroxine and free tri-iodothyronine in normal children.

Serum free thyroxine (fT4) and free tri-iodothyronine (fT3) were measured in 138 normal school children, adolescents and their younger siblings, whose ages ranged from 3 months to 18 years. Mean fT4 concentration (16.8 pmol/L) was similar to the adult mean concentration of 17 pmol/L and all the values were within the adult reference range. At all ages the fT3 range was considerably higher than the adult reference range and the overall mean fT3 concentration (8.3 pmol/L) was at the upper limit of normal in adults. In subjects aged 13-18 years the mean fT4 concentration was higher and the mean fT3 concentration lower than in children aged 0-12 years. The reasons for these differences are not known, but the data obtained provide a useful guide to the interpretation of serum free thyroid hormone measurements in children.

Adolescent↗

The natural history of tardive dyskinesia.

Follow-up data from the first 100 patients with early dyskinesia are presented. After an average of 40.9 months, the cohort showed statistically significant decreases in tardive dyskinesia (TD) ratings. After TD onset, ratings decreased for 4 years, then plateaued and rose during the 7th year. Age was not a negative prognostic factor in this cohort. Improvement in TD correlated significantly with fewer neuroleptic-free periods before and more neuroleptic-free periods after TD onset. Neuroleptic dosage correlated negatively with improvement in trunk and dystonia ratings. Improvement in TD is the usual finding in longitudinal studies of TD cohorts. Follow-up studies of neuroleptic-treated groups with varying proportions of patients showing TD, by contrast, tend to show increased TD because new TD cases more than offset improvement. A naturalistic study with pharmacotherapy tailored to the underlying psychiatric disorder and conducted long-term from TD onset is the ideal design for investigating the natural history of TD.

Adult↗

Characterization of an ATP-dependent DNA strand transferase from human cells.

We have characterized an enzymatic activity from human cell nuclei which is capable of catalyzing strand exchange between homologous DNA sequences. The strand exchange activity was Mg2+ dependent and required ATP hydrolysis. In addition, it was capable of promoting reannealing of homologous DNA sequences and could form nucleoprotein networks in a fashion reminiscent of purified bacterial RecA protein. Using an in vitro recombination assay, we also showed that the strand exchange activity was biologically important. The factor(s) responsible for the activity has been partially purified.

Adenosine Triphosphatases↗

Central nervous system lymphomatoid granulomatosis.

Lymphomatoid granulomatosis is a vasocentric lymphoreticular proliferative disease. Some patients go on to develop frank neoplasia. Central nervous system involvement with lymphomatoid granulomatosis has been reported previously in the literature. We are presenting a childhood case evaluated with magnetic resonance imaging and x-ray computerized tomography who developed severe tissue destruction with pleomorphic cellular infiltrate and oligoclonal light chains. This report adds information regarding neuroimaging as well as immunopathology data relevant to the basic biology of this disease.

Brain↗

Immunoassay for the detection of E. coli proteins in recombinant DNA derived human growth hormone.

An enzyme-linked immunosorbent assay (ELISA) has been developed for the quantitation of part-per-million levels of the most probable E. coli polypeptide (ECP) contaminants of E. coli produced biosynthetic human growth hormone (hGH). The antibody preparation, used for both coat and conjugate in this ELISA, was demonstrated to be reactive with the reference ECPs (a collection of the most probable protein contaminants) by both affinity chromatography and immunoblot analysis. Affinity purification of this antibody preparation using immobilized reference ECPs resulted in an assay with a higher signal-to-noise ratio and also 'normalized' the antibody population to approach stoichiometric equivalence with the immobilized ECPs. Reference ECPs, size fractionated by gel filtration, were quantitated in agreement with their absorbance at 280 nm. The assay was demonstrated to be specific for ECPs obtained from the hGH purification process. Since the purification of each recombinant DNA derived protein from E. coli requires its own unique process, this means that no generic ECP assay can be developed. It is felt that the criteria established for this assay provide a comprehensive approach to the development of quantitative multiple antigen immunoassays.

Antibody Specificity↗

Malignant histiocytosis in Bernese Mountain dogs.

Malignant histiocytosis was diagnosed in 10 male and 1 female Bernese Mountain Dogs. Nine of these dogs were closely related. The disease was characterized by a rapidly progressive and inevitably fatal course. Clinical signs varied, but lethargy, anorexia, weight loss, and respiratory and CNS abnormalities predominated. The lungs were the primary site of tumor involvement in 10 dogs. The eleventh dog had lymphadenopathy and severe anemia. Metastatic lesions were detected in all dogs. Anaplastic pulmonary carcinoma was diagnosed originally in 6 of the 11 cases, but this diagnosis was changed to malignant histiocytosis after electron microscopic examination of tissues and immunohistochemical identification of histiocytic markers in the tumor cells.

Animals↗

Quantitation of the ultra short acting beta-adrenergic antagonist flestolol in blood by liquid chromatography.

A sensitive, specific, reproducible, and convenient high-performance liquid chromatographic (HPLC) assay was developed for quantitation of the new ultra short acting beta-adrenergic antagonist, flestolol (1), in whole blood. The instability of the compound in blood was overcome by the esterase inhibitor, NaF, and deproteinization of blood samples with CH3CN:CH2Cl2 (2:5). The internal standard was p-ethoxyphenethyl alcohol. The compounds were back extracted from the CH3CN:CH2Cl2 phase into a small volume of pH 3-4 phosphate buffer and then separated on a reversed-phase C18 column with 0.05 M phosphate buffer (pH 3-4) in acetonitrile (4.6:1) as the mobile phase, and detected with an UV detector at 229 nm. The assay was linear with a blood concentration range from 10 to 1270 ng/mL (r2 greater than 0.998, p greater than 0.01), and reproducible with an overall CV of 8%. The assay procedure was used to determine the blood levels of flestolol intravenously infused into a male dog for 105 min at 230 micrograms/kg/min. The steady-state unchanged drug concentration of 5 micrograms/mL in blood was achieved within 10-20 min and declined biexponentially to 0.02 microgram/mL at 6 h following termination of the infusion.

Adrenergic beta-Antagonists↗

Stable gene amplification and overexpression of sodium- and potassium-activated ATPase in HeLa cells.

Cell lines stably resistant to ouabain were isolated from an unstably resistant HeLa line after growth in nonselective medium. Stable resistant lines bound ouabain at levels 10-fold higher than did HeLa cells and at similar levels to those bound by the unstable C+ line previously described (J. F. Ash, R. M. Fineman, T. Kalka, M. Morgan, and B. Wire, J. Cell Biol. 99: 971-983). Expression and synthesis of the Na+, K+ -ATPase alpha chain showed a similar amplification over that for HeLa cells by Western blots and [35S]methionine pulse-labeling. In addition, a glycoprotein labeled with [3H]fucose and comigrating with the Na+, K+ -ATPase beta chain was eight- to ninefold amplified in stably resistant lines. Dot blots with a cDNA clone specific for Na+, K+ -ATPase alpha chain gene sequences confirmed the amplification of this gene. Karyotyping suggested that the amplification is associated with an expanded, abnormal banded region on the long (q) arm of one chromosome 17.

Drug Resistance↗

CSF acid-base regulation and ventilation in iso- and hypocapnic Hacetate acidosis.

Intravenous infusion in conscious rabbits of Hacetate decreases both arterial CO2 partial pressure PaCO2 and cerebrospinal fluid (CSF) HCO3- more than observed with HCl or HNO3 infusion. These acids did not affect CSF HCO3- in isocapnic conditions, and this study asks whether Hacetate infusion will do so. Arterial, central venous, and cisterna magna catheters were implanted in pentobarbital-anesthetized rabbits and all subsequent measurements were performed in the conscious state. Hacetate was infused intravenously over 6 h to decrease plasma HCO3- the same amount in a group allowed to decrease its PaCO2 in response to the acid (hypocapnic) and one in which PaCO2 was maintained at control levels (isocapnic). CSF HCO3- decreased significantly in isocapnia, although the change was less than in hypocapnia. Stoichiometrically by 6 h the measured CSF HCO3- change was balanced by an increase in acetate in hypocapnia and the sum of an increase in acetate and a decrease in chloride in isocapnia. Mechanistically, net acetate entry into CSF appears to involve an exchange for chloride as proposed for NO3-/Cl- and a process that lowers CSF HCO3-. This process could be competitive replacement of HCO3- by acetate in the CSF production mechanism or nonionic diffusive entry of Hacetate into CSF with subsequent titration of HCO3-. The decreases in CSF HCO3- result from the acetate mechanism and the hypocapnic effect on Cl- and HCO3-. The greater ventilatory response results from the greater CSF acidification or a specific effect of acetate per se.

Acetates↗

Infarction of a growth hormone-secreting macroadenoma during a TRH test.

Pituitary infarction occurring immediately after TRH injection (200 micrograms) is reported in a patient with gigantism due to a growth hormone-secreting pituitary macroadenoma. Evidence of infarction was seen in CSF and in serial CT scans. Regression of symptoms and sign of acromegaly, abolition of abnormal growth hormone secretion, and virtually complete anterior and partial posterior pituitary failure rapidly followed. The infarction was probably initiated by a hypertensive response to TRH. TRH testing in acromegalic subjects may require smaller doses of TRH to avoid unwanted pressor responses.

Acromegaly↗

The porcine LH/hCG receptor. Characterization and purification.

Porcine luteal LH/hCG receptor (LH/hCG R) was solubilized with 70-80% recovery from the crude plasma membrane fraction by Triton X-100 in the presence of 25% glycerol and protease inhibitors. The solubilized receptor maintained 90% of original activity at -60 degrees C for 90 days. Equilibrium association constant (Ka) values of 1.92, 2.22, and 2.03 X 10(10) M-1 were observed for the whole homogenate, plasma membrane fraction, and solubilized LH/hCG R preparations, respectively. The specific binding capacity for the same fractions were 49, 70, 55 fmol/mg protein, respectively. Complexes of LH/hCG R and Triton X-100 were resolved into two components with approximate Mr = 2.7 X 10(5) and 5.4 X 10(5) by gel filtration on Sepharose 6B and two glycoprotein components by chromatography on concanavalin A-Sepharose. Solubilized porcine LH/hCG R was purified by two cycles of affinity chromatography on highly purified hCG-Sepharose with an overall recovery of 30-35% of the initial activity in the Triton extract. Purified porcine LH/hCG R had a specific binding capacity of 2300 pmol/mg protein and a Ka = 1.5 X 10(10) M-1. Silver staining of sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels demonstrated that the major protein in porcine LH/hCG R preparations has Mr = 68,000. A weakly staining band at Mr = 45,000 was also observed in the purified receptor preparation. Analysis of iodinated purified LH/hCG R by autoradiography has confirmed these results. Porcine LH/hCG R was purified 40,000-fold by this method.

Animals↗

Chronic lead poisoning in a two-year-old child. A 12-month follow-up study.

X-ray examination of the broken arm of a two-year-old child demonstrated the presence of lead deposits in the bone. Chelation treatment with calcium-EDTA was undertaken. The results obtained over three months of treatment, and those obtained at the follow-up examination 12 months later are reported. The need to analyse the blood as well as the urine to obtain an accurate measure of lead concentrations is emphasized.

Arm↗

Anticholinergic challenge and neuroleptic withdrawal. Changes in dyskinesia and symptom measures.

Benztropine mesylate (intravenous [IV] and oral) challenge was compared with brief neuroleptic withdrawal on dyskinesia ratings and symptom measures. Thirty-six neuroleptic-treated patients underwent a placebo-controlled acute IV challenge with 2 mg benztropine and a placebo-controlled two-week trial of oral benztropine mesylate (2 mg three times a day), followed by a double-blind placebo-controlled neuroleptic withdrawal involving four weeks of dose tapering and six weeks of placebo treatment. Benztropine given IV had no significant effect. Orally administered benztropine, however, led to statistically significant increases in dyskinesia and dysphoric mood. The brief neuroleptic withdrawal significantly increased dyskinesia scores and dysphoria and resulted in early termination of therapy in 12 of 36 patients (33%) due to symptom exacerbation. There was a striking absence of correlation between dyskinesia change measures brought about by benztropine and changes following neuroleptic withdrawal. Therefore anticholinergic challenge does not appear to be a fruitful procedure for identifying patients with covert dyskinesia.

Administration, Oral↗

Prevalence of cytomegalovirus antibody in nursing personnel.

To evaluate the risk to nurses of childbearing age of acquiring cytomegalovirus (CMV) infection during the care of patients at high risk of the infection, 374 female hospital employees (288 nursing personnel) were interviewed and screened for antibody to CMV. Fifty-six percent of the population surveyed had antibody to CMV as measured by an immunofluorescent assay. Among nursing personnel, analysis of antibody prevalence by job title, work area, and duration of work showed no association between seropositivity and either current or past exposure to "high-risk" patients, such as infants and immunosuppressed individuals. Age, race (non-white), and the number of pregnancies reported by participants were significantly associated with the presence of antibody. Among 73 employees of a children's hospital, the prevalence of CMV antibody was 41%. This survey suggests that hospital nursing is not a major risk factor for acquiring CMV infection. However, this finding needs further evaluation in a prospective study of seroconversion rates among seronegative nurses.

Adult↗