Search PubMed⌕ Search

Biomedical subjects

D Baines

Publications and source records attributed to D Baines.

At least 37 records · Page 2Linked to original sources
PubMed1996

Predicting activity and workload in general practice from the demographic structure of the practice population.

OBJECTIVES: The managerial requirements of budget-setting and performance monitoring in general practice (primary care) in the UK require an understanding of the causal relationship between practice activities and the characteristics of both the practice and its patients. This study sought to model the determinants of three major components of general practice activities (consultations, prescribing costs and referrals to secondary care), paying particular attention to the influence of the demographic structure of the patient list. METHODS: Stepwise regression analysis was carried out on data for 98 practices in the county of Lincolnshire using 12 independent variables pertaining to patient and practice characteristics plus 14 statistical measures derived from the demographic structure of the patients registered with the practice. RESULTS: Robust statistical models were estimated for the three dependent variables, of which list size emerged as the most significant independent variable. In addition, six other independent variables, including the patients' unemployment rate, fundholding status and single-handed status, were statistically significant in one or more of the equations. Variables based on the demographic structure of the practice population also appeared in each model. The Jarman score and degree of urbanization did not achieve statistical significance. CONCLUSIONS: Activity and workload in general practice can be predicted from routine data. Such models are of particular value for planning and financial management when demographic change in practice populations is anticipated.

Budgets↗
PubMed1995

Evaluation of chick embryo neural retinal cell culture as a screen for developmental toxicants.

This paper describes a study to evaluate the concordance with in vivo results of an in vitro screen for developmental toxicants. The screen is a primary culture of chick embryo neural retina cells (CERC) which undergo processes of cell-cell recognition and interaction, growth, and differentiation over a 7-day culture period. Each of these developmentally significant events is measured separately as formation of multicellular aggregates, protein content, and glutamine synthetase activity, respectively. A total of 45 chemicals, 24 of which have been shown to be teratogenic at some dosage to mammalian embryos in utero, 7 of which are embryotoxic (but not teratogenic) in utero at high dosage, and 14 of which have not produced developmental toxicity in vivo, were evaluated in this assay by investigators who were blinded to the identity of the chemicals. Chemicals were tested up to concentrations that were frankly cytolethal, or up to a maximum of 5 mg/ml. Chemicals were present only during the first 24 hr of culture. The chemicals were selected to be representative of a variety of chemical classes (e.g., solvents, metals, food additives, anticonvulsants, antineoplastics). In several cases, pairs of structurally similar compounds with different developmental toxic potencies (e.g., valproate and 2-en-valproate, formamide, and N,N-dimethylformamide) were tested. Of the 31 developmental toxicants, 25 affected at least one endpoint in the assay at concentrations which are achievable in vivo (i.e., below the systemic concentration at a lethal dose), yielding a false-negative rate of 19%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Parental presence at induction of anaesthesia: a survey of N.S.W. hospitals and tertiary paediatric hospitals in Australia.

We undertook a survey of N.S.W. hospitals and tertiary paediatric hospitals in other States to determine their practice in relation to parental presence at induction of anaesthesia of children. There were 135 responses to 174 questionnaires. Twenty-one indicated that no children were anaesthetized at their institution and one was inadequately filled out. One hundred and thirteen questionnaires were assessed. Only 44% of departments had an official policy on parental attendance. A quarter of all hospitals described their facilities as entirely suitable, and a half compromised to allow parents to be present. The remaining quarter described their facilities as unsuitable. Overall, two-thirds of hospitals never or only sometimes had parents present at induction, and this applied equally to day stay patients and inpatients. Tertiary hospitals were more likely to have parents present, however they were more likely to have suitable facilities. The most common reason cited for parental attendance was parental expectation of being present, closely followed by the individual anaesthetist's philosophy. The most common reason for parents not attending was the individual anaesthetist's philosophy, followed by inadequate staffing.

Adult↗
PubMed1994

A polymerase chain reaction study of the stability of Ig heavy-chain and T-cell receptor delta gene rearrangements between presentation and relapse of childhood B-lineage acute lymphoblastic leukemia.

Ig heavy-chain (IgH) and partial V delta 2-D delta 3 T-cell receptor (TCR) gene rearrangements were investigated, by polymerase chain reaction (PCR) amplification and sequence analysis, in 52 patients at presentation and first relapse and in 14 at both first and second relapse of B-lineage acute lymphoblastic leukemia. In combination, these techniques amplified one or more clonal markers at presentation in 90% of patients (IgH-PCR, 75%; V delta 2-D delta 3-PCR, 46%; both, 33%). Changes in the pattern of amplification between presentation and first relapse were seen in 31% of patients positive by IgH-PCR at presentation and in 25% of those positive by TCR delta-PCR. Only 3 patients showed complete change in their rearrangements, which is suggestive of relapse with a new clone. Furthermore, despite the high reported rates of oligoclonality and clonal evolution at the IgH locus, the results presented show that false-negative minimal residual disease (MRD) detection can be avoided by designing D-N-J probes to all presentation rearrangements. Using a PCR approach for both gene markers, false-negative testing because of clonal evolution would have only occurred in 3 (8%) of the IgH-positive patients, in contrast to 5 (21%) of V delta 2-D delta 3-positive patients. Combining these two systems increases the proportion of patients open to study to 90%, allows comparative studies of the sensitive of the two methods, and reduces the rate of false-negative assessment of MRD caused by clonal evolution to less than 10%. We conclude that large prospective PCR studies of MRD detection should examine gene rearrangements at multiple loci to maximize their applicability and to minimize false-negative relapse prediction.

Adolescent↗
PubMed1994

Octopamine enhances phagocytosis in cockroach hemocytes: involvement of inositol trisphosphate.

Octopamine and 5-hydroxytryptamine (5-HT) were previously shown to affect phagocytosis in cockroach hemocytes through unidentified receptor-mediated events. In the present study, we examined the ability of 5-HT and octopamine to enhance inositol trisphosphate (IP3) production using hemocyte membranes of the American cockroach, Periplaneta americana. Octopamine enhanced IP3 production with a maximal peak at 100 nM. Similarly, 5-HT enhanced IP3 production with a maximal effect at 10 nM. The effects of 5-HT and octopamine are not additive, suggesting that both are working through the same receptor. Phentolamine, a general octopamine antagonist, blocked the effects of octopamine and 5-HT, while a mammalian 5-HT2 antagonist that blocks 5-HT-sensitive receptors in insect peripheral tissue, ketanserin, did not. A pharmacological profile indicates that the receptor is similar to an octopamine1-type. Octopamine at 1 microM increased phagocytosis in cockroach hemocytes exposed to Staphylococcus aureus in vitro, and this effect was mimicked by IP3 (10 microM). The octopamine-treated hemocytes were shown to increase IP3 production in the latter stage of phagocytosis. Adult cockroaches exposed to an LD50 dose of S. aureus in conjunction with either 0.1 mM octopamine or the octopamine1 agonist, clonidine, had higher survival rates compared to saline-treated cockroaches. Correspondingly, the octopamine1 antagonist, chlorpromazine, partially blocked the octopamine-mediated increase in cockroach survival.

Analysis of Variance↗
PubMed1994

Specificity domain localization of Bacillus thuringiensis insecticidal toxins is highly dependent on the bioassay system.

The Bacillus thuringiensis crylA(a) and crylA(c) gene specificity regions were probed by creating and testing hybrid toxins both in vivo and in vitro against cultured insect cells or dissociated midgut epithelial cells. Toxin threshold dose determinations revealed that CrylA(c) is highly active against cultured Choristoneura fumiferana cells (CF-1) whereas CrylA(a) is nontoxic. In live insect bioassays, a reversed order of toxicity was observed. Hybrid analysis revealed that the CrylA(c) toxicity-determining region is located between codons 258 and 510. Two smaller subsections of this region (residues 258-358 and 450-510) were able to confer toxicity, although at lower levels, and one region (358-450) was present where progressive substitutions of crylA(a) with crylA(c) sequences had no effect. Exchanging the non-homologous N-terminal regions of CrylA(c) with CrylE suggested that the N-terminus does not play a role in specificity. One hybrid clone, MP80, displays a 99.3% homology to CrylA(b) but shows an 800-fold increase in toxicity to CF-1 cells relative to that shown by CrylA(b). Direct comparison between live Bombyx mori bioassays and a newly developed in vitro lawn assay using dissociated midgut epithelial cells from the same insect revealed striking differences in toxicity. The toxicity-determining region for B. mori larvae was determined to be between codons 283 and 450, although the 450-620 codon region may exert an influence on toxicity. In general, native or hybrid toxins showing little or no insect intoxication were very active against the epithelial cells, suggesting that factors other than toxin amino acid sequence play an important role in determining toxin specificity.

Amino Acid Sequence↗
PubMed1993

Activation of both Wnt-1 and Fgf-3 by insertion of mouse mammary tumor virus downstream in the reverse orientation: a reappraisal of the enhancer insertion model.

In retrovirus-induced tumors, proviral DNA is commonly found next to or within a cellular proto-oncogene such that transcription of the gene is influenced by the viral promoter or enhancer. Extensive surveys of naturally occurring tumors reveal that proviruses integrated on the 3' side of the gene are usually in the same transcriptional orientation, suggesting a model in which the bidirectional viral enhancer acts primarily on the closest promoters. Here we describe a virally induced mammary tumor that appears to contradict these ideas since the Wnt-1/int-1 and Fgf-3/int-2 proto-oncogenes have both been activated by mouse mammary tumor virus (MMTV) DNA integrated 3' of the gene in the opposite transcriptional orientation. However, by cloning the relevant DNAs, we show that these are not simple proviral insertions. In the Wnt-1 locus, there is an additional LTR immediately adjacent to the 3' end of the MMTV provirus, while in Fgf-3, the provirus has sustained a deletion that removes the 5' LTR, gag, and most of pol. These structural alterations can be reconciled with the enhancer insertion model by postulating that the viral enhancer can only function if it is not transcribed.

Animals↗
PubMed1992

Effects of sodium butyrate on the expression of sodium channels by neuronal cell lines derived from the rat CNS.

We have studied the effects of sodium butyrate on cell morphology and the expression of mRNAs encoding voltage-gated sodium channels in five neuronal cell lines, B35, B50, B65, B103 and B104, all derived from the rat CNS. The cells were grown in medium supplemented with 2.5 mM sodium-n-butyrate and examined daily by phase-contrast microscopy. Sodium butyrate caused slowing of cell division and the formation of longer and more highly branched cytoplasmic processes than were present in untreated cells. Expression of sodium channel mRNA was analysed by PCR with primers that allow the transcripts encoding the different types of sodium channel to be distinguished according to the lengths of the PCR products. The identity of the PCR products was confirmed by restriction enzyme digestion. Southern blotting and hybridization with internal radiolabelled probes. Prior to sodium butyrate treatment, expression of sodium channel mRNA was largely restricted to B50 and B104 cells: B50 cells showed expression of rat brain types I and II sodium channel and B104 cells expressed rat brain type III sodium channel. After treatment for 5 days with sodium butyrate, sodium channel mRNA was detected in all five cell lines. In addition to type I and type II sodium channel, B50 cells expressed rat brain type III sodium channel. These three types of sodium channel were also expressed by B35, B65 and B103 cells. Even after butyrate treatment, B104 cells expressed only type III sodium channel. The treatment also induced expression of rat skeletal muscle SkM1 sodium channel in B35 cells but only trace amounts in the other neuronal cell lines.

Animals↗
PubMed1991

Chick embryo neural retina cell culture as a screen for developmental toxicity.

An in vitro screen for developmental toxic potential of chemicals using primary cultures of chick embryo neural retina cells is described. The neural retinas of incubation Day 6.5 White Leghorn chick embryos are dissociated into single cells, which are subsequently maintained in a rotating suspension culture. Under normal circumstances, neural retina cells form spheroidal aggregates of a consistent size over the first 24 hr of culture, an event which is dependent on competent cell-cell interactions. Over the remaining 7-day period of culture, cells continue to divide and grow, and differentiation takes place. Each of these developmentally important events--aggregation, growth, and differentiation--is objectively and quantitatively measured as aggregate size and number, aggregate protein content, and glutamine synthetase (a marker of differentiation) activity, respectively. The effects on each developmental endpoint of 22 chemicals, 14 of which have been demonstrated to be developmentally toxic in one or more mammalian species in vivo, and 8 of which are not developmentally toxic, were evaluated. Chemicals were tested up to a concentration of 40 mM, or until marked cytolethality was observed. Of the known developmental toxicants, all but one, 2-methoxyethanol, affected one or more endpoints in the assay. The teratogenic metabolite of 2-methoxyethanol, 2-methoxyacetic acid, was active in the assay. None of the 8 nondevelopmental toxicants had any effect up to a concentration of 40 mM, or at biologically achievable concentrations (e.g., in vivo systemic concentrations at the LD50). Thus, the assay is 95% concordant with in vivo results for this set of chemicals. Quantitative comparisons were made (1) between developmentally toxic ip dosages in rats or mice in vivo and effective concentrations in the chick retina cell culture, and (2) between effective concentrations in chick retina cell culture and rodent whole embryo culture. In the first instance, 71% of the comparisons, and in the second instance, 89% of the comparisons, were within the same order of magnitude (and usually within a factor of two), indicating that the chick retina cell culture is also concordant with developmental toxic potency. Last, it was observed that test agents differentially affect developmental endpoints. Because the assay's endpoints are measured separately and objectively, it may be possible to use the assay to evaluate the effects of test agents on cellular development.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Effects of lysosomal proteinase inhibition on the development of the rat embryo in vitro.

Altered lysosomal function in the visceral yolk sac can result in abnormal development. As proteolysis is an important function of the rodent visceral yolk sac during early and mid-gestation, we characterized the lysosomal proteolytic enzyme activity of this extraembryonic membrane and determined the effects of inhibitors of protein degradation on embryonic development. Constituent activities of cysteine and aspartic acid proteinases were measured in rat visceral yolk sac on gestation day 12, and the effects of the cysteine proteinase inhibitors leupeptin, E-64 [trans-epoxysuccinyl-l-leucylamido(4-guanido)butane] and N-ethylmaleimide and the aspartic acid proteinase inhibitor pepstatin were determined in Sprague-Dawley rat embryos cultured in vitro from gestation days 10-12. It was determined that only cysteine proteinases, primarily cathepsins B and L, are active in the mid-gestation visceral yolk sac. The cysteine proteinase inhibitors leupeptin and E-64 both produced a concentration-related decrease in embryonic growth, as measured by crown-rump length, somite number, and embryonic protein content, and a concentration-related increase in incidence of abnormalities. A characteristic pattern of abnormalities was produced which involved a decrease in neural tube volume and the formation of a subectodermal blister opposite the point of attachment of the vitelline vessels. At high concentrations, anophthalmia was also observed. The decreased neural tube volume was associated with increased osmolality of the exocoelomic fluid, the major extraembryonic fluid compartment. It is possible that the osmotic change decreased neural tube volume by causing water to move to the compartment with a higher solute concentration, out of the embryo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Interspecies comparisons of A/D ratios: A/D ratios are not constant across species.

The hypothesis that the ratio of the adult (A) and developmental (D) toxicity of a chemical is constant across animal species has been proposed as the basis for identifying developmental hazards, both from traditional developmental toxicity screens using laboratory mammals and from alternative systems such as the coelenterate Hydra attenuata. The purpose of this study was to determine whether A/D ratios are constant across species. The developmental and adult toxicity of 14 chemicals was assessed in four phylogenetically different species. The chemicals tested were aminopterin, bromodeoxyuridine, cadmium chloride, caffeine, congo red, dinocap, dinoseb, diphenylhydantoin, epinephrine, ethylenethiourea, 2-methoxyethanol, mirex, all-trans-retinoic acid, and trypan blue. These chemicals are representative of a variety of toxic mechanisms and a range of potencies. Species used were the CD-1 mouse (Mus musculus), South African clawed frog (Xenopus laevis), fathead minnow (Pimephales promelas), and fruit fly (Drosophila melanogaster). The mouse is a commonly used model for developmental toxicity. The other species are known to be sensitive to mammalian toxicants and have well-studied embryologies. Mice were exposed to chemicals either po or by sc injection using a standard Segment II protocol in which pregnant mice are administered the test agent on a daily basis from Gestation Days 6 to 15, adult toxicity is evaluated during and after treatment, and developmental toxicity is evaluated in fetuses at term. The exposure duration spans the period of organ formation in the embryo. The other species were exposed to test agents for a developmentally comparable period. This was from blastulation (shortly after fertilization) to the free-swimming tadpole stage in Xenopus (4 days); from blastulation to the free-swimming fry stage in Pimephales (7 days); and for the entire larval period, the period of development of the imaginal discs, in Drosophila (6 days). Adults of each species were exposed to test agents for 4, 7, and 6 days, respectively. The route of exposure was via the water column in the two aquatic species and via the diet in Drosophila. Statistical lowest observed effect level (LOEL) and no observed effect level (NOEL) values were generated for adult and developmental toxicity in each species. A/D ratios were calculated using both LOEL and NOEL values.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1991

Immunochemical detection of sodium channel in human tissue and cell lines.

Mouse monoclonal antibodies have been raised to the C-terminal region of rat type II voltage-dependent sodium channel. One of these, designated 13A4-G4, recognizes a 260 Kd putative sodium channel protein in human fetal brain, heart and skeletal muscle, at 14-18 weeks of gestation. Faint immunoreactivity is also present in human fetal kidney but none has been detected in human fetal liver, lung or spleen. The antibody reacts in both western blots and immunocytochemical preparations with the human neuroblastoma cell lines SK-N-SH and SK-N-MC, the rhabdomyoblastoma cell line TE671, Y79 retinoblastoma cells and IPSB-18 astrocytoma cells. No 13A4-G4 immunoreactivity has been detected in several human cell lines derived from tissues that do not normally express sodium channels.

Animals↗
PubMed1990

Embryonal disposition of salicylate: in vivo-in vitro comparisons.

The distribution of salicylate to embryonal compartments for in situ and in vitro rat embryos under equivalent exposure conditions, and salicylate disposition in the in vivo mid-gestation embryo and late gestation fetus, were compared. Pregnant Sprague-Dawley CD rats were exposed to steady-state blood levels of salicylate by infusing 14C-salicylic acid iv for a 24 hour period from gestation day 11.5 to 12.5. Cultured Sprague-Dawley rat embryos (in medium consisting of 100% male rat serum) were exposed to the steady-state 14C-salicylate concentration achieved in maternal serum in vivo for the same 24 hour developmental period. At the end of the exposure period radioactivity in visceral yolk sac, extra-embryonic fluid and embryos, and in maternal tissues, was measured. The distribution of salicylate to embryonal tissues was statistically comparable in vivo and in vitro, although the embryos in vitro accumulated slightly (but not significantly) less of the chemical. There was considerable binding of salicylate by maternal serum and culture medium proteins: less than 20% of the chemical was free at the 40 micrograms/ml concentration used in this experiment. Consequently, the salicylate concentration in embryonal compartments appeared to be quite low when compared to the surrounding serum/medium, but was actually equal to or greater than the concentration of unbound salicylate in serum or culture medium. The proportion of free salicylate in serum increased at concentrations higher than 40 micrograms/ml, resulting in somewhat higher concentrations of salicylate in in vitro embryos and extraembryonic fluid (as compared to medium) when cultured in the presence of 200 or 400 micrograms/ml salicylate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗