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Biomedical subjects

A Moore

Publications and source records attributed to A Moore.

At least 289 records · Page 16Linked to original sources
PubMed1992

In-vitro DNA synthesis in Leydig and other interstitial cells of the rat testis.

Replicative DNA synthesis (125I-labelled iododeoxy-uridine incorporation) was measured in interstitial cells prepared from rat testes and separated by Percoll density gradient centrifugation. Leydig cells were identified by 125I-labelled human chorionic gonadotrophin (hCG) binding and 3 beta-hydroxysteroid dehydrogenase histochemistry. Continuous density gradients indicated that interstitial cell DNA synthesis was not associated with Leydig cells, and was greater in cells from the immature than from the mature rat testis. Fractionation of cells by discontinuous density gradients into Leydig cell-rich and -depleted pools did not result in a similar enrichment of DNA synthesis. Treatment of the adult rat with hCG increased DNA synthesis into both fractions but oestrogen had no effect. DNA synthesis was greater in cells from the immature rat but, in contrast to the adult, in-vivo hCG treatment had no effect, whilst oestrogen decreased synthesis. To characterize the cells synthesizing DNA further, interstitial cells were prepared from testes in which the Leydig cells were depleted by in-vivo treatment with ethane dimethanesulphonate (EDS) or depleted in their germ cells by treatment in utero with busulphan. EDS treatment had no effect on DNA synthesis by the interstitial cells in spite of the 125I-labelled hCG binding being markedly reduced. Similarly, busulphan treatment was also without effects upon DNA synthesis. Fluorescence-activated cell cycle analysis of cells from both fractions from germ cell-depleted testes indicated that only a small proportion (3%) of the interstitial cells were actively dividing and this was almost doubled in cells from the germ cell-depleted immature rat testes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Cytosine arabinoside and cisplatin for advanced breast cancer. A phase II study of the Cancer and Leukemia Group B.

Forty-four women with advanced breast cancer participated in a prospective clinical trial to evaluate the efficacy and toxicity of a regimen consisting of cytosine arabinoside and cisplatin. All patients had previously received chemotherapy. Three patients (7%) responded to therapy with response durations of 153, 160, and 441 days. The median time to disease progression and median survival time in all 44 patients were 2.3 and 5 months, respectively. This regimen had significant toxicity, with most patients experiencing severe or life-threatening hematologic, renal, or infectious complications. This regimen cannot be recommended for previously treated patients with advanced breast cancer.

Adult↗
PubMed1991

Diphenylene iodonium, an inhibitor of free radical formation, inhibits platelet aggregation.

Diphenylene iodonium is an inhibitor of the enzyme NADPH-oxidase and prevents the generation of oxygen-derived free radicals in neutrophils (Cross and Jones, 1986). Here we show that diphenylene iodonium (0.25-2 microM) inhibited, according to the dose, thrombin-induced platelet-aggregation in human washed platelets and ADP-induced platelet aggregation in platelet-rich plasma. At the concentrations which inhibited platelet aggregation diphenylene iodonium did not alter platelet concentrations of cAMP or cGMP but enhanced the anti-platelet activity of iloprost, sodium nitroprusside or cultured endothelial cells. These findings highlight the importance of free radicals as platelet pro-aggregatory agents.

Adenosine Diphosphate↗
PubMed1991

Cell cycle-dependent phosphorylation of human DNA polymerase alpha.

The expression of DNA polymerase alpha, a principal chromosome replication enzyme, is constitutive during the cell cycle. We show in this report that DNA polymerase alpha catalytic polypeptide p180 is phosphorylated throughout the cell cycle and is hyperphosphorylated in G2/M phase. The p70 subunit is phosphorylated only in G2/M phase. This cell cycle-dependent phosphorylation is due to cell cycle-dependent kinase(s) and not to phosphatase(s). In vitro evidence indicates the involvement of p34cdc2 kinase in the mitotic phosphorylation of DNA polymerase alpha. Tryptic phosphopeptide maps demonstrate that peptides phosphorylated in vitro are identical to those phosphorylated in vivo. DNA polymerase alpha from mitotic cells is found to have lower affinity for single-stranded DNA than does polymerase alpha from G1/S phase cells. These results imply that the mitotic phosphorylation of polymerase alpha may affect its physical interaction with other replicative proteins and/or with DNA at the replication fork.

Amino Acid Sequence↗
PubMed1991

Influence of menstrual cycle and gender on alprazolam pharmacokinetics.

The effects of menstrual cycle phases and gender on alprazolam pharmacokinetics were evaluated in normal volunteers. Alprazolam (1 mg) was administered to seven women during the late follicular and luteal phases of the menstrual cycle and to eight men on one occasion. No difference in alprazolam pharmacokinetic parameters was observed during the menstrual cycle phases. Mean alprazolam clearance (+/- SD) was 0.0037 +/- 0.0009 ml/hr during the follicular phase and 0.0036 +/- 0.001 ml/hr during the luteal phase (p greater than 0.05, difference not significant). With use of weight as a covariant, there was no difference in alprazolam pharmacokinetic parameters between women and men. Mean alprazolam clearance (+/- SD) was 0.0036 +/- 0.0009 ml/hr in women compared with 0.0041 +/- 0.0006 ml/hr in men (p greater than 0.05, difference not significant). Although alprazolam metabolism was similar on the 2 days tested, alterations may occur at other times during the menstrual cycle. Further investigation is needed to understand the effects of menstrual cycle phases and gender on drug metabolism.

Adult↗
PubMed1991

Quantifying exposure in occupational manual tasks with cumulative trauma disorder potential.

A method of describing the musculoskeletal loads in the hand and wrist during manual tasks is presented. A profile of twelve factors is used to quantify the exposure of applicable soft tissues to modes of loading suggested as being related to a number of chronic, work-related musculoskeletal disorders such as chronic muscle strain, tenosynovitis, and carpal tunnel syndrome. These factors include estimates of tendon loads and movement, frictional work done on the tendon sheaths, and muscle activation determined using electromyography. The response of these measures to changes of force, repetition, and posture was studied using eight conditions of a simulated task utilizing a pistol grip tool. Measures of tendon frictional work and dynamic electromyographic activity best paralleled the injury outcomes of an epidemiological study using similar task definitions (Silverstein et al. 1986). This field-usable system is being used currently to investigate the relationship between occupational exposure and musculoskeletal disorders.

Biomechanical Phenomena↗
PubMed1991

Drug effects on a novel in vitro model of cartilage breakdown.

A new in vitro model for studying cartilage breakdown has been utilised in this work. Polymorphonuclear neutrophils (PMNs) with phorbol myristate acetate (PMA) were layered onto 2 microns cryostat sections of bovine nasal cartilage. After incubation, the sections were fixed, stained, and the amount of glycosaminoglycan (GAG) contents measured by microdensitometry. PMNs caused GAG loss from sections and this was greatly enhanced when the PMNs were activated by PMA. Various pharmacological agents were then added to the system, namely acetyl salicylic acid, indomethacin, ibuprofen, piroxicam, dexamethasone, D-penicillamine, chloroquine and BN50548. The drugs tested had no direct effect on cartilage matrix, nor did they affect GAG loss from sections treated with non-stimulated PMNs. However, BN50548, a novel protease inhibitor, afforded a dose response protection of cartilage section from GAG loss by PMA stimulated PMNs. This model may prove to be of value in screening novel antiproteases with chondroprotective activity.

Animals↗
PubMed1990

Analysis of major androgen-regulated cDNA clones from the rat epididymis.

Four abundant cDNA clones have been isolated from a rat epididymal cDNA library. Northern blot analysis has shown that these clones partially encode 4.5 kb, 2.8 kb, 1.2 kb and 0.85 kb mRNAs and that their expression is not detectable in total RNA preparations from heart, kidney, liver or testis. Fourteen days after castration the levels of the 2.8 kb, 1.2 kb and 0.85 kb transcripts were greatly reduced whereas the 4.5 kb mRNA was undetectable. Subsequent treatment of castrated rats with testosterone for 1 day resulted in a complete restoration of the pre-castration steady-state levels of the 2.8 kb and 0.85 kb mRNAs, restoration of the 4.5 kb mRNA to 70% of pre-castration levels, and a slight over-induction of the 1.2 kb mRNA. Analyses of separate regions of the epididymal tract showed that expression of the 2.8 kb and 1.2 kb mRNAs increased towards the distal end of the epididymis, while the 4.5 kb and 0.85 kb transcripts were primarily synthesised in the caput region.

Amino Acid Sequence↗
PubMed1990

Plasticity in the aging brain. Reversibility of anatomic, metabolic, and cognitive deficits in normal-pressure hydrocephalus following shunt surgery.

The course of idiopathic normal-pressure hydrocephalus was studied in a 78-year-old woman with a 4-year history of progressive dementia who underwent neuropsychologic testing, quantitative x-ray computed tomography, magnetic resonance imaging, and positron emission tomography with fludeoxyglucose F 18 to measure rates of regional cerebral glucose utilization. Preshunt cognitive testing demonstrated progressive deterioration during 2 years, and positron emission tomography showed significant reductions in regional cerebral glucose utilization of 34% to 49% as compared with age- and sex-matched control subjects in frontal, temporal, parietal, and whole brain regions. Periodic testing, carried out during a 2-year period after shunt surgery, showed steady improvement in clinical status. Parallel to the clinical changes, there was a significant reversal in neuropsychologic test scores with increased brain volume and increased regional cerebral glucose utilization in several brain regions. These results documented the considerable potential for recovery of compromised brain function in older subjects even after 4 years of progressive brain disease.

Aged↗
PubMed1990

Bromfenac, acetaminophen, and placebo in orthopedic postoperative pain.

In a double-blind, placebo-controlled, single-dose, parallel-group study, oral doses (5, 10 and 25 mg) of the prostaglandin synthetase inhibitor bromfenac were compared with acetaminophen (1000 mg) and placebo for postoperative orthopedic pain. Analgesic measurements were made by nurse observers by use of standard verbal rating and visual analog scales. For most pain intensity and pain relief measurements, 1000 mg acetaminophen was statistically superior to placebo, demonstrating assay sensitivity, and 10 and 25 mg doses of bromfenac were statistically better than both placebo and 5 mg bromfenac for ordinal and analog ratings of pain intensity and pain relief; 25 mg bromfenac produced significantly longer time to remedication than acetaminophen. The 5 mg dose of bromfenac was statistically superior to placebo for some measures, including remedication time. There were no untoward adverse effects or alterations in vital signs. Overall, 10 mg bromfenac produced analgesia equivalent to that of 1000 mg acetaminophen in this pain context.

Acetaminophen↗
PubMed1990

Road safety and drink-driving: the knowledge and opinions of male and female adolescents.

This paper reports on a structured questionnaire survey of high school students from years 8, 9 and 10 and their knowledge and opinions on issues relating to general road safety and drink-driving. A representative sample of this larger group was then interviewed in more depth. The results are discussed in terms of previous surveys of adolescents' attitudes and knowledge on these issues and the educational questions that arise in the light of reported sex differences.

Journal Article↗
PubMed1990

Percutaneous absorption and skin decontamination of PCBs: in vitro studies with human skin and in vivo studies in the rhesus monkey.

Knowledge of the entry of polychlorinated biphenyls through the skin into the body and subsequent disposition aids estimation of potential for human health hazard. [14C]Aroclor 1242 and [14C]Aroclor 1254 were separately administered intravenously and topically to rhesus monkeys. Following iv administration, 30-d excretion was 39.4 +/- 5.9% urine and 16.1 +/- 0.8% feces (total 55.5 +/- 5.1%) for Aroclor 1242, and 7.0 +/- 2.2% urine and 19.7 +/- 5.8% feces (total 26.7 +/- 7.5%) for Aroclor 1254. Mineral oil and trichlorobenzene are common PCB cosolvents in transformers. Skin absorption of Aroclor 1242 was 20.4 +/- 8.5% formulated in mineral oil and 18.0 +/- 3.8% in trichlorobenzene (p greater than .05). Absorption of Aroclor 1254 was 20.8 +/- 8.3% in mineral oil and 14.6 +/- 3.6% in trichlorobenzene (p greater than .05). PCBs are thus absorbed through skin, and excretion from the body is slow. Vehicle (trichlorobenzene or mineral oil) did not affect percutaneous absorption. In vitro skin absorption in human cadaver skin did not correlate with in vivo findings. This was due to lack of PCB partition from skin into the water receptor fluid, even with addition of 6% Oleth 20 (Volpo 20) solubilizer. Skin decontamination of PCBs showed soap and water to be as effective as or better than the solvent ethanol, mineral oil, and trichlorobenzene in removing PCBs from skin. There is a dynamic time lapse for PCBs between initial skin contact and skin absorption (irreversible removal). Thus initially most PCBs could be removed from skin, but this ability decreased with time to the point where at 24 h only about 25% of the initial PCB skin dose could be recovered with skin washing.

Administration, Topical↗
PubMed1990

An 18-kDa androgen-regulated protein that modifies galactosyltransferase activity is synthesized by the rat caput epididymidis, but has no structural similarity to rat milk alphalactalbumin.

Galactosyltransferase and alphalactalbumin-like activities have been reported to be present in the post-testicular fluids of the male reproductive tract. In the lactating mammary gland, these activities constitute the lactose synthetase complex. Kinetic parameters and acceptor specificities previously reported, along with recent amino acid sequence analysis argue against the mammary gland and epididymal activities being products of the same gene. In this paper we present cell-free translation of rat epididymal mRNA and Northern blot analysis of epididymal mRNA hybridized with authentic rat alpha-lactalbumin cDNA supporting this lack of identity and describe the differential synthesis and secretion of the androgen-regulated 18 kDa component of the so-called rat epididymal alphalactalbumin-like complex along the length of the epididymis. We conclude that although the 18 kDa component of the so-called epididymal alphalactalbumin moiety (E alpha LA) is capable, in common with a number of unrelated molecules, of modifying galactosyltransferase acceptor specificity in vitro, there is no primary structural similarity between it and authentic rat mammary alphalactalbumin. In view of the fact that the activity of E alpha LA is 1/100th that of authentic milk alphalactalbumin, we suggest that it may not be of physiological importance and that modification of galactosyltransferase activity may not be the function of the 18 kDa molecule.

Amino Acid Sequence↗