Biomedical subjects
Publications and source records attributed to V Moore.
A series of substituted 2-aminopyridines was prepared and evaluated as inhibitors of human nitric oxide synthases (NOS). 4,6-Disubstitution enhanced both potency and specificity for the inducible NOS with the most potent compound having an IC50 of 28 nM.
BACKGROUND: Magnesium therapy is sometimes continued after an episode of threatened preterm labour in an attempt to prevent the onset of further preterm contractions. OBJECTIVES: The objective of this review was to assess the effects of magnesium maintenance therapy on preventing preterm birth after threatened preterm labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Randomised controlled trials of magnesium therapy given to women after threatened preterm labour. DATA COLLECTION AND ANALYSIS: Trial quality assessment and data extraction were done independently by two reviewers. MAIN RESULTS: Two trials were included. Both were of poor quality and neither study included any long-term follow up of infants. The incidence of preterm birth or perinatal mortality was not reduced by magnesium maintenance therapy compared to alternative therapy or no treatment. REVIEWER'S CONCLUSIONS: There is not enough evidence to show that magnesium maintenance therapy is effective in preventing preterm birth after an episode of threatened preterm labour.
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Lewis (1999) argued that effects of age of acquisition (AoA) are entirely attributable to cumulative frequency. He reported an instance-based model in which the number of instances of the stimulus stored in memory predicts reaction time. We note four aspects of the literature on AoA that cannot be explained by this instance-based approach. Firstly, an effect of AoA has been observed in the absence of an effect of frequency. Secondly, an effect of AoA has been observed when cumulative frequency has been controlled. Thirdly, the effect of AoA is dependent on task. Fourthly, the effect of word frequency is dependent on stimulus modality. Lewis reported an experiment in which participants make a decision based on identity-specific semantic information to celebrity faces to demonstrate an effect of the number of instances in memory, which he interpreted as an effect of AoA. We note that effects of AoA have been found in lexical and perceptual tasks, but to date all attempts to demonstrate an advantage for early-acquired items in semantic classification tasks have failed. We conclude that the effects of AoA cannot be attributed solely to the effects of cumulative frequency.
A major focus in gene therapy has been the use of recombinant viruses to deliver genes in vivo. Although this approach shows much promise, there are many safety concerns associated with the use of viral materials in the treatment of human diseases. Our alternative cell-based gene therapy approach utilizes endothelial cells (Pro 175) isolated from the murine embryonic yolk sac. These endothelial cells were evaluated for their potential use in gene therapy as a gene delivery platform. As a test model, we used these cells to deliver apolipoprotein E (apoE) in the murine apoE knockout atherosclerosis model. The lack of apoE protein in these animals results in high levels of serum cholesterol and formation of severe aortic plaques and lesions at a young age. After transplantation of the apoE secreting Pro 175 endothelial cells into apoE-deficient mice, serum cholesterol levels were measured at 2 week intervals. During the 3 months after the initiation of these experiments, levels of cholesterol in the animals having received the apoE secreting endothelial cells were statistically lower compared with the levels of age-matched controls having received non-secreting endothelial cells. Concomitant with cholesterol reduction, atherosclerotic aortic plaques were noticeably reduced in the experimental apoE+ animals. These results highlight the potential of these unique endothelial cells as an efficient delivery platform for somatic gene therapy.
Three experiments examined whether famous faces would be affected by the age at which knowledge of the face was first acquired (AoA). Using a multiple regression design, Experiment 1 showed that rated familiarity and AoA were significant predictors of the time required to name pictures of celebrities' faces and the accuracy of producing their names. Experiment 2 replicated an effect of AoA using a factorial design in which other attributes of the celebrities were matched. In both Experiments 1 and 2, several ratings had been collected from participants before naming latency data were collected. Experiment 3 investigated the accuracy and latency of naming celebrities without any prior exposure to the stimuli. An advantage for naming early acquired celebrities was observed even on the first presentation. The participants named the same celebrities in three subsequent presentations of the stimuli. The effect of AoA was not significant on the fourth presentation. The implications of these results for models of face naming and directions for future research are discussed.
Two experiments are reported that tested predictions derived from the framework of face, object, and word recognition proposed by Valentine, Brennen, and Brédart (1996). The findings were as follows: (1) Production of a celebrity's name in response to seeing the celebrity's face primed a subsequent familiarity decision to the celebrity's printed name. The degree of repetition priming observed was as great as that observed when a familiarity decision to the printed name was repeated in the prime and test phases of the experiment. (2) Making a familiarity decision to an auditory presentation of a celebrity's name primed a familiarity decision to the same celebrity's name presented visually. The magnitude of cross-modality priming was as great as the magnitude of within-modality repetition priming. This result for people's names contrasted with the effects observed in lexical decision tasks, in which no reliable cross-modality priming was observed. The results cannot be accounted for by previous models of face and name processing. They show a marked contrast between processing people's names and processing words. The results support the framework proposed by Valentine et al. (1996). The implications for models of speech production, perception, and reading are discussed, together with the potential of the methodology to elucidate our understanding of proper name processing.
OBJECTIVE: To quantify the matrix metalloproteinase-induced neoepitope F(M/V)DIPEN (Phe-[Met/Val]-Asp-Ile-Pro-Glu-Asn341) in guinea pig and rabbit cartilage during aging. METHODS: Cartilage was taken from the stifle joint, nasal septum, and xiphoid process in guinea pigs and rabbits at selected ages. The cartilage was then extracted and evaluated for F(M/V)DIPEN levels by radioimmunoassay. RESULTS: In the 3 tissues studied, there were major increases in F(M/V)DIPEN levels during skeletal maturation and aging in both the guinea pig and rabbit cartilage. Except for spontaneous osteoarthritis that develops in guinea pigs with aging, increases in the neoepitope were not correlated with arthritis pathology. CONCLUSION: Increases in the level of F(M/V)DIPEN in cartilage occur as a result of skeletal maturation and aging. This physiologic accumulation of F(M/V)DIPEN in cartilage should be considered when using the neoepitope as a disease marker in arthritis.
We tested the hypothesis that a heritable EEG trait, the low voltage alpha (LV), is associated with psychiatric disorders. Modest to moderate evidence for genetic linkage of both panic disorder and the low voltage alpha trait to the same region of chromosome 20q has recently been reported, raising the issue of whether there is a phenotypic correlation between these traits. A total of 124 subjects including 50 unrelated index subjects and 74 relatives were studied. Alpha EEG power was measured and EEG phenotypes were impressionistically classified. Subjects were psychiatrically interviewed using the SADS-L and blind-rated by RDC criteria. Alcoholics were four times more likely to be LV (including so-called borderline low voltage alpha) than were nonalcoholic, nonanxious subjects. Alcoholics with anxiety disorder are 10 times more likely to be LV. However, alcoholics without anxiety disorder were similar to nonalcoholics in alpha power. An anxiety disorder (panic disorder, phobia, or generalized anxiety) was found in 14/17 LV subjects as compared to 34/101 of the rest of the sample (P < 0.01). Support for these observations was found in the unrelated index subjects in whom no traits would be shared by familial clustering. Lower alpha power in anxiety disorders was not state-dependent, as indicated by the Spielberger Anxiety Scale. Familial covariance of alpha power was 0.25 (P < 0.01). These findings indicate there may be a shared factor underlying the transmissible low voltage alpha EEG variant and vulnerability to anxiety disorders with associated alcoholism. This factor is apparently not rare, because LV was found in approximately 10% of unrelated index subjects and 5% of subjects free of alcoholism and anxiety disorders.
A study of parents' strategies to communicate with their young visually-impaired children has implications for all health visitors working with young children, write Vanessa Moore and Helen McConachie. The study highlights the important role of naturally-occurring communicative exchanges between parent and young child in promoting language development.
The VFe protein of alternative nitrogenase, isolated from Azotobacter vinelandii, strain LS15 and designated as Av1', has been investigated by Mössbauer spectroscopy. The Mössbauer spectrum of the dithionite-reduced Av1', recorded at 4.2 K with a 60-millitesla magnetic field applied parallel to the gamma-beam, is a superposition of three spectral components: 1) a complex spectrum (the M component) with magnetic hyperfine structures attributed to the paramagnetic FeV cofactor, 2) a component (the P component) consisting of three quadrupole doublets identifiable as the Fe2+, D, and S doublets similar to those observed for the P cluster pairs in MoFe proteins, and 3) a minor (4% of total absorption) quadrupole doublet attributable to adventitiously bound iron. The observed 4.2-K parameters for the Fe2+ (delta EQ = 2.99 mm/s and delta = 0.64 mm/s), D (delta EQ = 0.75 mm/s and delta = 0.63 mm/s), and S (delta EQ = 1.2 mm/s and delta = 0.65 mm/s) iron sites and their temperature dependence are very similar to those observed for the P cluster pairs in the conventional MoFe proteins. Similar to those of the MoFe protein, strong field spectra indicate that these doublets are associated with a diamagnetic system. Their percent absorption intensities (Fe(2+)/D/S = 13.0:32.2:6.8) determined at 4.2 K after the removal of the contributions from the adventitiously bound iron are comparable to those of the P cluster pairs in MoFe proteins. These observations established that Av1' also contains P cluster pairs that are identical, in both composition and quantity, to those of the MoFe proteins; i.e. each molecule contains two P cluster pairs and each pair is formed by two Fe2+, five D, and one S iron sites. Considering that 52% absorption of the P component corresponding to two 8Fe clusters, the remaining 48% absorption determined for the M component is consistent with two 7Fe-containing FeV cofactors/molecule of Av1'. The fact that both P cluster pairs are found in the diamagnetic states implies that the S = 3/2 and S = 1/2 signals detected in earlier EPR measurements are associated with the FeV cofactor and suggests a spin mixture for the FeV cofactor in the dithionite-reduced Av1'.
This paper presents a comparison of the early language of nine blind and nine severely visually impaired children, with no other impairments, who were recruited from paediatric vision clinics in London and assessed in the second and third year of life using the Reynell-Zinkin Developmental Scales. Further information on milestones and content of early expressive language was obtained from parents' diary recordings of their children's emerging words. It is concluded that severely visually impaired children's expressive language tends to develop later than that of sighted children. The effect of children having even a small amount of vision could be discerned in their early words. The developmental course appears to be particularly variable for blind children, with implications for parental counselling.
The neural cell adhesion molecule, N-CAM, is a well-characterized component of nervous system morphogenesis and histogenesis. It mediates aggregation of neurons by binding homophilically to N-CAM on apposing cells. Different forms are generated through alternative splicing of one gene and varied amounts of carbohydrate determine binding strength. This review summarizes results of contemporary studies which link N-CAM components with activity involving the maintenance and reorganization of the brain following injury. Current studies which suggest mechanisms of function are also included.
Three experiments are reported in which a repetition priming technique was used to investigate whether recognition of a person's surname which is also a known word (e.g. Baker) activates the lexical representation that mediates word recognition. Experiment 1 showed that a familiarity decision to familiar full names produced an effect of repetition priming on subsequent lexical decision to words that were presented in the initial task as surnames. Experiment 2 demonstrated that, conversely, a lexical decision primed subsequent familiarity decision to full names involving the same word. Experiment 3 showed that repeating the same decision during the initial and test phases did not produce a larger repetition priming effect than that obtained when the task at test differed from the prime task (name familiarity decision vs lexical decision or vice versa). The results are interpreted as support for the view that repetition priming is due to repeated activation of representations that are accessed by both common names and proper names.
Three hundred and eight subjects were screened over the phone for admission to an inpatient alcohol treatment research unit. Using a structured interview, the prospective patients were asked questions regarding demographics, drinking history, previous treatments, physical health, family history, and a detailed history of past and present substance use. Drug use was studied as regular use versus no use or brief experimental use of five drug categories: cannabinoids, stimulants, sedatives, opiates, and hallucinogens. Fifty-one percent of the men and 48% of the women reported regular use of one or more of the drugs in addition to alcohol. For women, the amount of alcohol intake was positively correlated with use of stimulants (r = .32, p = .001), cannabinoids (r = .24, p = .019), sedatives (r = .30, p = .003), and hallucinogens (r = .30, p = .003). For men, correlations between the amount of alcohol intake and drug use were weaker but significant for stimulants (r = .21, p = .002), opiates (r = .15, p = .028), and hallucinogens (r = .15, p = .029). Women with alcoholic mothers displayed higher alcohol intake than women with nonalcoholic mothers (p = .02) and also showed more frequent use of most drugs. Although men with alcoholic fathers also showed greater alcohol intake compared to men with nonalcoholic fathers, the two groups did not differ in drug use. Younger subjects of both sexes were more likely to use cannabinoids, stimulants, opiates, and hallucinogens. Alcohol and sedative use was relatively constant across all age groups.
OBJECTIVE: To examine the in vivo expression of the matrix metalloproteinase stromelysin in the synovium and articular cartilage of rabbits injected intraarticularly with recombinant human interleukin-1 beta (IL-1). METHODS: The direct isolation of messenger RNA (mRNA) from articular cartilage without the prior isolation of chondrocytes is described. The in vivo expression of stromelysin was examined at the mRNA level by Northern blot analysis, and at the protein level by in situ immunolocalization and by enzyme-linked immunosorbent assay. RESULTS: In the synovium of IL-1-injected joints, stromelysin mRNA levels were highest at 4 hours and declined to background levels within 24 hours. In the cartilage of IL-1-injected joints, stromelysin mRNA was elevated at 4 hours and continued to increase until 8 hours, before declining. Stromelysin mRNA expression preceded a similar increase in stromelysin protein levels in both synovium and cartilage. CONCLUSION: Intraarticular injection of IL-1 induced the endogenous expression of stromelysin mRNA and protein in both synovium and cartilage. The kinetics of stromelysin expression correlated well with the accumulation of stromelysin and proteoglycan in synovial fluids. Therefore, the de novo synthesis of stromelysin in cartilage may have contributed to the loss of proteoglycan from that tissue.
Left ventricular hypertrophy (LVH), as assessed by ECG or echocardiography, is a powerful independent coronary risk factor. The present overview of 104 studies sets out to compare the ability of various forms of antihypertensive therapy to reverse LVH as assessed by echocardiography. Most observations involved four classes of treatment--combination therapy, ACE inhibitors, beta-blockers and calcium antagonists (mainly dihydropyridines). The former two therapies were significantly more effective than the latter two in reversing LV mass, independently of length of time on treatment and degree of fall in blood pressure. Possible reasons for these differences are discussed. The clinical significance of these results is unclear although preliminary data indicate that regressing LVH is associated with fewer cardiovascular events.