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Biomedical subjects

M J Moore

Publications and source records attributed to M J Moore.

At least 145 records · Page 8Linked to original sources

Analysis of phosphoramide mustard by reversed-phase ion pair high pressure liquid chromatography.

The analysis of phosphoramide mustard by reversed-phase ion pair high pressure liquid chromatography using ultraviolet detection is described. The method will enable measurement of serum concentrations of phosphoramide mustard over a period of approximately 24 h after an i.v. dose of 60 mg/kg of cyclophosphamide and requires 0.5 ml of serum or plasma. The between-day precision of the assay at concentrations of 0.34, 2.76, and 6.90 mg/L gave coefficients of variation of 16, 10, and 9%, respectively. The percentage analytical recovery of phosphoramide mustard is 35%. Preliminary results providing pharmacokinetic data on two adults undergoing high-dose cyclophosphamide treatment prior to bone marrow transplant are presented.

Chromatography, High Pressure Liquid↗

Temporal changes in a complex spectral profile.

The spectral properties of a complex stimulus (rippled noise) were varied over time, and listeners were asked to discriminate between this stimulus and a flat-spectrum, stationary noise. The spacing between the spectral peaks of rippled noise was changed sinusoidally as a function of time, or the location of the spectral peaks of rippled noise was moved up and down the spectrum as a sinusoidal function of time. In most conditions, listeners were able to make the discriminations up to rates of temporal modulation of 5-10 cycles per second. Beyond 5-10 cps the rippled noise with the temporally varying peaks was indiscriminable from a flat (nonrippled) noise. The results suggest that for temporal changes in the spectral peaks of rippled noise, listeners cannot monitor the output of a single (or small number of) auditory channel(s) (critical bands), or that the mechanism used to extract the perceptual information from these stimuli is slow. Temporal variations in the spectral properties of rippled noise may relate to temporal changes in the repetition pitch of complex sounds, the temporal properties of the coloration added to sound in a reverberant environment, and the nature of spectral peak changes such as those that occur in speech-formant transitions. The results are relevant to the general issue of the auditory system's ability to extract information from a complex spectral profile.

Auditory Pathways↗

Maintenance of progesterone-facilitated sexual behavior in female rats requires continued hypothalamic protein synthesis and nuclear progestin receptor occupation.

The role of ongoing progesterone-directed protein synthesis and hypothalamic cell nuclear progestin receptor occupation in maintaining the duration of the period of sexual receptivity was determined in ovariectomized rats treated with 500 micrograms progesterone 44 h after receiving 2 micrograms estradiol benzoate. Injection of the protein synthesis inhibitor anisomycin (100 mg/kg BW) either 2 or 10 h after progesterone treatment resulted in decreased levels of both receptive and proceptive sexual behavior. Similarly, injection of RU 486, an antiprogestin, 2, 6, or 10 h after progesterone injection resulted in inhibition of sexual behavior within 4-8 h after administration. Using a modified cell nuclear isolation technique for the exchange assay of nuclear-bound progestin receptors, elevated levels of progestin binding in hypothalamic cell nuclear fractions were detected as late as 14 h after progesterone injection. By 18 h after progesterone injection, nuclear progestin receptor levels had returned to baseline, a time when the period of sexual behavior had terminated in similarly treated animals. These data suggest that continued progesterone action in hypothalamic cell nuclei is required for the maintenance of progesterone-facilitated sexual behavior in the female rat. Furthermore, they suggest that progesterone action maintains sexual responsiveness by altering the synthesis of a short-lived protein or set of proteins.

Animals↗

Therapeutic drug monitoring in oncology. Problems and potential in antineoplastic therapy.

Therapeutic drug monitoring is now widely used in many areas of medicine. With its proliferation has come an understanding of the clinical situations in which it is likely to be of value. Factors that can limit the usefulness of therapeutic drug monitoring and situations where it is less likely to be of benefit have also been identified. At present, the routine use of therapeutic drug monitoring in antineoplastic therapy is limited to measurement of plasma methotrexate concentrations after high-dose methotrexate therapy. The lack of a more widespread application of therapeutic drug monitoring in oncology has been due to deficiencies in knowledge about the clinical pharmacology of antineoplastic agents and to factors specific to the chemotherapy of neoplasms. These factors include the broad heterogeneity of malignant neoplasms, the complexities of the drug-tumour interaction, difficulties in assessment of this interaction and the use of combinations of antineoplastic agents with cumulative efficacies and toxicities. Despite these problems, there are many areas in antineoplastic therapy where the use of therapeutic drug monitoring could prove of benefit. The prevention of the chronic pulmonary toxicity of bleomycin, the assessment of the bioavailability of oral chemotherapy, and monitoring drug disposition in the presence of hepatic or renal dysfunction are just some of the potential applications. If recent emphasis on dose as a critical factor in the success of cancer chemotherapy is substantiated, then the need to apply therapeutic drug monitoring within oncology will become more pressing.

Antineoplastic Agents↗

A quantitative ultrastructural study of rat tendon from birth to maturity.

In a morphometric analysis of rat tail (RTT) and extensor digitorum longus (EDLT) tendons in rats from birth to 12 weeks of age it was found that the volume fraction of tenoblasts and the surface density of their plasma membranes fell sharply. The collagenous extracellular fraction rose in a reciprocal manner over the same period. The volume fraction of the tenoblast rough endoplasmic reticulum stayed more or less constant from newborn to 12 weeks. The collagen fibril diameters displayed a sharp unimodal distribution at birth, but at 12 weeks became bimodally distributed and of greater range, especially in RTT. Generally, observations were similar to data previously published in qualitative studies, but there were small differences between RTT and EDLT which may be accounted for by differences in function.

Aging↗

Location of ubiquinone-10 (CoQ-10) in phospholipid vesicles.

Egg yolk phosphatidylcholine (PC) liposomes were prepared by ultrasonic irradiation. At least 25 mol% of coenzyme Q-10 (CoQ-10) can be incorporated nonstoichiometrically into PC liposomes. Electron microscopy showed no visible influence of CoQ-10 on the membrane structure. Nuclear magnetic resonance spectra of sonicated PC liposomes containing CoQ-10 showed two peaks (3.82 and 3.98 ppm) due to CoQ-10 methoxyl protons and a 'high-field component' (1.52 and 1.58 ppm). The areas of these peaks were inversely related and influenced by the time of ultrasonic irradiation. After short sonication the low-field positions (3.98/1.58 ppm) are favoured, after long sonication the high-field positions (3.82/1.52 ppm). No gradual shift of the two peaks is observed. The 'critical' liposome diameter was found to be between 500 to 700 A. Lanthanide induced pseudocontact shift on CoQ-10 resonances ('high-field component' and methoxyl) does not lead to a split of the peaks and the difference between them remains constant. It is concluded that CoQ-10 is incorporated into the membrane core, beyond C-2 of the PC acyl chains, with two bilayer curvature-dependent resonance positions.

Animals↗

HLA antigens in Guillain-Barré syndrome.

We compared Guillain-Barré syndrome (GBS) cases reported from cities in the United States in 1976-1977 with spouse or associate controls to detect possible HLA associations. HLA-A11 was somewhat less common among 92 cases than among 100 controls (p = 0.04). The 38 patients and 42 controls vaccinated against A/NJ/76 differed slightly in overall distribution of B locus antigens (p = 0.06), but the individual HLA-B antigen associations were more easily explained by chance. The 54 unvaccinated cases showed no apparent relation to HLA type. These findings should encourage further immunogenetic study of etiologically related GBS cases.

Adolescent↗

Depressed macrophage functions at temperatures below 37 degrees C.

Immunobiological properties of guinea pig and human peritoneal macrophages were studied at temperatures ranging from 25 degrees C to 37 degrees C. Glass adherence, random migration, response to MIF and killing of Salmonella typhimurium and Saccharomyces cerevesiae by guinea pig macrophages were decreased with temperatures below 37 degrees C. Killing of Sacch. cerevesiae by human macrophages was also reduced at temperatures less than 37 degrees C. Acid phosphatase and beta-N-acetylglucosaminidase (NAG) activity assayed at 37 degrees C did not change when the cells were preincubated for 1 and 5 hours at various temperatures. Impaired macrophage function with subnormal temperatures may contribute to enhanced susceptibility to infection of patients with chronic diseases such as renal failure and cirrhosis.

Acetylglucosaminidase↗

Strychnine blocks binaural inhibition in lateral superior olivary neurons.

The present study seeks to identify neurotransmitters mediating binaural inhibition in lateral superior olivary nucleus neurons. Neurons in this auditory structure receive inputs from both ears and are thought to code for localization of sound in space. Iontophoretic application of glycine during monaural stimulation was found to mimic the inhibition observed with binaural stimulation. Binaural inhibition was blocked by application of the glycine receptor antagonist, strychnine, as were the effects of iontophoretic application of glycine. The post-strychnine recovery time course for return of synaptically mediated binaural inhibition and recovery of the effects of iontophoretic glycine application were identical. Although the superior olivary complex (SOC) neurons displaying binaural inhibition could in some cases be inhibited by GABA, the binaural inhibition rarely was blocked by iontophoretic application of the GABA receptor antagonist, bicuculline. These findings suggest that glycine may be a neurotransmitter mediating binaural inhibition in certain SOC neurons and that the projection to the lateral superior olivary nucleus from the medial nucleus of the trapezoid body may be glycinergic.

Acoustic Stimulation↗

Analgesia and increases in limbic and cortical MOPEG-SO4 produced by periaqueductal gray injections of morphine.

Analgesia and changes in limbic and cortical concentrations of the major brain noradrenaline metabolite, 3-methoxy-4-hydroxy-phenylethylene glycol sulphate (MOPEG-SO4), were investigated in rats following the bilateral injection of morphine into the periaqueductal gray (PAG). Morphine, at a dose of 5 micrograms per bilateral site, produced a significant antinociceptive effect within 15 min of injection. This effect, as measured by the tail flick analgesic test, remained constant at a level of approximately 75% of the maximum for 60 min. Significant increases in limbic and cortical MOPEG-SO4 were also observed 15, 30 and 60 min after the 5 micrograms bilateral PAG injection of morphine. However, MOPEG-SO4 concentrations exhibited a sharp peak in both brain areas at 30 min. Analgesia and the regional increases in MOPEG-SO4 were antagonized by the prior systemic injection of naloxone (1 mg kg-1, i.p.). Thus, analgesia and increases in noradrenaline metabolism in two brain regions appear to be mediated by the specific activation of opiate receptors in the PAG. Although these findings indicate that brain noradrenergic systems may be involved in the mediation of morphine analgesia, the lack of a strict temporal relationship between antinociceptive action and increases in MOPEG-SO4, suggests that analgesia cannot be totally attributed to changes in brain noradrenergic transmission.

Analgesics↗