Search PubMed⌕ Search

Biomedical subjects

D Hughes

Publications and source records attributed to D Hughes.

At least 271 records · Page 15Linked to original sources
PubMed1988

Incantations in the dark: Medicaid, managed care, and maternity care.

Public program reforms in the 1980s have substantially increased the numbers of poor pregnant women potentially eligible for Medicaid coverage. Structural deficiencies in the Medicaid program, together with inadequate arrangements in managed-care plans, however, have not led to generally acceptable levels of maternity care. Demonstration projects indicate that Medicaid can be modified cost effectively to underwrite early, continuous, and comprehensive care delivery. Recommendations are suggested for eligibility guarantees, enrollment safeguards, benefit and treatment protocols, provider recruitment, quality control, and sufficient payment rates to overcome barriers to adequate levels of material health care.

Delivery of Health Care↗
PubMed1988

RAS mutations in myelodysplasia detected by amplification, oligonucleotide hybridization, and transformation.

Members of the RAS gene family have been implicated in many neoplasms with activating mutations around amino acid positions 12 and 61. We have assessed the mutational activation of H, K, and NRAS in myelodysplasia (MDS) by polymerase chain reaction and hybridization with synthetic oligonucleotide probes. Using this method, point mutations in codons 12/13 and 61 of these RAS genes were detected in 20 of 50 patients including two with refractory anemia with ringed sideroblasts (RARS). Ten normal individuals had no detectable RAS mutations. In 11 instances, DNA from patients with detectable RAS mutations were shown to register in either NIH3T3 focus-forming or nude mouse tumorigenicity assays. In addition, one patient (RARS) was shown to have an activated NRAS gene detected by a tumorigenicity assay and Southern blot analyses. Two MDS patients had mutations detected in two different RAS genes. DNA from one of these patients was observed to give rise to transformants with activated N and HRAS. Two patients with detectable NRAS mutations in the MDS stage progressed to AML and DNA from the AML stage registered positively in a transformation assay with NRAS activation. These results show that RAS mutations can occur at early, as well as late, stages of leukemic progression. The incidence of RAS mutations appears to be significantly higher in CMML than in the other subgroups (p = 0.02).

Adult↗
PubMed1987

Mutants of elongation factor Tu promote ribosomal frameshifting and nonsense readthrough.

This is the first report of ribosomal frameshifting promoted by mutants of the elongation factor Tu (EF-Tu). EF-Tu mutants can suppress both -1 and +1 frameshift mutations. The level of nonsense readthrough is also increased at some UGA (this paper) and UAG (Hughes, 1987) sites by these mutants. Suppression occurs when a mutant tuf allele is paired with a wild-type copy of the other tuf gene but is most efficient when both tuf genes are mutant. Frameshifting mediated by the tuf alleles studied, tufA8 and tufB103, is not general; indeed most frameshift mutations are not suppressed. Several possible mechanisms by which mutant EF-Tu may cause frameshifting are discussed.

Alleles↗
PubMed1987

Mutant forms of tufA and tufB independently suppress nonsense mutations.

The level of nonsense suppression in Salmonella typhimurium carrying error-enhancing mutations in either or both of the genes coding for the elongation factor EF-Tu has been measured. Suppression of both UGA and UAG is observed. There is no significant suppression of any of six UAA sites tested. Nonsense suppression does not require that both genes for EF-Tu be mutant. Strains carrying one mutant and one wild-type tuf gene suppress nonsense mutations. The level of suppression increases approximately additively when both tuf genes are mutant. It is suggested that these mutant forms of EF-Tu act independently of each other to suppress nonsense mutations. Suppression is not observed at all UGA and UAG sites, but instead shows a strong site specificity.

Codon↗
PubMed1987

Oxygen dependence of binding of misonidazole to rodent and human tumors in vitro.

Misonidazole, a 2-nitroimidazole, has been shown to form metabolically induced adducts to cellular molecules at a very high rate in the absence of oxygen, and this rate decreases substantially as the oxygen concentration increases. Thus, it has considerable potential as a marker for hypoxic, radiation resistant cells in tumors. The dependence of the rate of adduct formation (binding) on oxygen concentration was studied for EMT6/Ed, Walker 256, and Dunning R3327-AT rodent tumors and for two human colon carcinomas, a human melanoma, and a human breast carcinoma. Fragments of these tumors were incubated with [14C]- or [3H]misonidazole in vitro at several oxygen concentrations and the quantity of misonidazole bound was determined from autoradiographs as a function of distance from the surfaces of the fragments. The Km of binding inhibition (oxygen concentration for half-maximal binding) for the tumors varied by a factor of 10. The range was centered on the range of values reported for the Km of cellular radioresistance (oxygen concentration for half-maximal radioresistance). The patterns of binding at depth within the tumor fragments indicated that gradients of cellular waste products and nutrients other than oxygen had minimal effects on binding. All tumors were capable of metabolizing oxygen to levels sufficiently low to yield the maximal binding rate, but the distance of penetration of oxygen varied, indicating a range of at least 4 in rates of oxygen consumption. The ratio of misonidazole bound by stromal tissue versus tumor cells ranged from 0.9 for a colon tumor to 0.3 for a breast tumor. These properties of misonidazole binding indicate that it should be a good marker for radiobiological hypoxia in tumors, providing adequate controls can be performed.

Adenocarcinoma↗
PubMed1987

Assessment of adrenocortical activity in term newborn infants using salivary cortisol determinations.

Salivary cortisol concentrations were collected every 2 hours over a 24-hour period in eight healthy 2-day-old term neonates. Two maxima in cortisol output were noted, neither being related to the time of day or time since birth. Salivary cortisol concentrations ranged from 2.5 to 57.4 nmol/L (0.09 to 2.08 micrograms/dL), and throughout the 24 hours showed considerable variation (21% to 42%) not related to the state of arousal. The validity of the method was confirmed by collecting matched plasma and saliva samples from another group of 36 neonates. The correlation between plasma and saliva cortisol was r = 0.83. We suggest that salivary cortisol is a useful, noninvasive method of studying adrenocortical status in the newborn infant.

Adrenal Cortex↗
PubMed1987

Somatization disorder in the community. A study of diagnostic concordance among three diagnostic systems.

Somatization disorder, the presentation of multiple somatic complaints in multiple organ systems, can be diagnosed by three roughly comparable diagnostic systems: the Washington University Feighner criteria, the Research Diagnostic Criteria, and DSM-III criteria. This study evaluates diagnostic concordance for somatization disorder in these three diagnostic systems using data gathered in the National Institute of Mental Health-sponsored Epidemiologic Catchment Area Program at four sites. Data gathered through use of the Diagnostic Interview Schedule at the Duke, Johns Hopkins, Washington, and Yale University sites indicate that each criterion set identifies a somewhat different group of respondents. Feighner criteria identify the fewest number of respondents, followed by DSM-III criteria and the Research Diagnostic Criteria. Demographic, symptomatic, health utilization, and other severity indices indicate that the respondents identified by each group are very similar and that all diagnostic groups are clearly distinguishable from the normal population.

Adolescent↗
PubMed1987

A patch clamp study of gamma-aminobutyric acid (GABA)-induced macroscopic currents in rat melanotrophs in cell culture.

1. The macroscopic currents induced in cultured rat melanotrophs by exogenous gamma-aminobutyric acid (GABA) were analysed using the patch clamp recording technique. 2. Using various concentrations of intra- and extracellular chloride it was demonstrated that the conductance activated by GABA was chloride selective. Since these currents were blocked with bicuculline and enhanced with chlordiazepoxide the involvement of GABAA receptors similar to those in the CNS is indicated. 3. When chloride was symmetrically distributed across the membrane the voltage/current relationship was linear; pronounced rectification of GABA mediated currents was evident when there was an asymmetrical distribution of chloride. 4. With concentrations of GABA greater than 10 microM a fading of the current was seen during prolonged (5-10 s) applications. This effect appeared to be due to a decline of conductance rather than a shift of the chloride equilibrium potential. 5. Values for the Hill coefficient derived from dose-response curves suggested that the binding of 2 molecules of GABA to the receptor is required for the activation of the chloride channel. 6. There was no indication of a direct, GABAB receptor-mediated change of conductance.

Action Potentials↗
PubMed1987

Caesium ions activate chloride channels in rat cultured spinal cord neurones.

1. Caesium ions (Cs+), applied extracellularly, caused a decrease in the input resistance of cultured spinal cord (s.c.) neurones and depolarized the neurones when they contained 140 mM-CsCl. 2. The reversal potential for Cs+-activated currents shifted 56 mV on average for a 10-fold reduction in the intracellular chloride ion (Cl-) activity, indicating that the Cs+-activated currents were specific to Cl-. 3. The activation of Cl- currents by Cs+ was not due to the depolarization-evoked release of neurotransmitter from presynaptic terminals. We therefore suggest that Cs+ were acting directly on the extracellular surface of the s.c. neurones to activate Cl- currents. 4. Cs+-activated currents showed desensitization in the presence of 140 mM-Cs+. 5. The log-log plot of the dose-response data could be fitted with a straight line with a slope of 1.7 +/- 0.4 (n = 6), indicating that at least 2 Cs+ were needed to activate a single Cl- channel. The KD of the Cs+-induced response was greater than 69 mM. 6. In outside-out patches Cs+ activated single Cl- channels. These channels were not activated by sodium or potassium ions. 7. The Cs+-activated channels displayed a total of five distinct conductance states which had mean conductances of 20, 30, 43, 66 and 92 pS. The 30 and 43 pS states were the most frequently occurring states. 8. The conductance states of the Cs+-activated channel have the same conductances as those reported for gamma-aminobutyric acid (GABA)- and glycine-activated channels in rat s.c. neurones. We therefore conclude that Cs+ activate the same type of Cl- channel as GABA and glycine through an unidentified receptor.

Action Potentials↗
PubMed1987

Blood spot glucocorticoid concentrations in ill preterm infants.

The adrenocortical response to stress was studied longitudinally in 10 ill preterm infants using measurements of cortisol and 170H-progesterone concentrations in filter paper blood spots. Mean cortisol and 170H-progesterone concentrations reached a peak of 2200 nmol/l and 65 nmol/l, respectively, between the third and fifth days of life. These concentrations far exceeded those observed in older children and adults subjected to stress as a result of surgery. Further pulses of endogenous cortisol production of 4000 nmol/l or more occurred in association with clinical complications such as intraventricular haemorrhage. These results indicate that infants undergoing intensive care are unduly stressed. Consideration should be given to providing enough sedation and appropriate analgesia for ill preterm infants during painful procedures such as insertion of venous cannulae and arterial puncture.

17-alpha-Hydroxyprogesterone↗
PubMed1987

Stressful life events and the onset of a generalized anxiety syndrome.

In a study of 2,902 subjects from the National Institute of Mental Health Epidemiologic Catchment Area Project in North Carolina, the association between life events and the onset of new cases of generalized anxiety syndrome varied across demographic subgroups and type of life event measure. Men reporting four or more life events had a risk of generalized anxiety syndrome 8.5 times that of men reporting zero to three life events; no association was found for women. Both men and women reporting one or more unexpected, negative, very important life events had a threefold increase in the risk of developing generalized anxiety syndrome.

Adolescent↗
PubMed1986

The effect of interleukin-1 on connective tissue metabolism and its relevance to arthritis.

Interleukin-1 (IL-1) is the name given to a family of related proteins showing a variety of activities. It was originally shown to be produced by monocytes and macrophages but is now known to be produced by numerous cell types, including synovial cells. From the point of view of arthritis, its most interesting activities are those on connective tissue cells in vitro. These include stimulation of production of prostaglandins, plasminogen activator and metalloproteinases such as collagenase and proteoglycanase. IL-1 is also mitogenic for synoviocytes and bone cells, and can alter rates of production of extracellular matrix constituents. The presence of IL-1 in synovial fluids from rheumatoid and osteoarthritic joints and its actions on connective tissues in vitro suggest that IL-1 may play an important role in the pathogenesis of arthritis. There are several potential cellular sources of IL-1 in the inflamed rheumatoid joint and interactions between these cells, T lymphocytes and plasma cells may continually induce IL-1 so contributing to the chronicity of the disease. The mechanism of action of IL-1 on connective tissue cells is at present uncertain though preliminary studies suggest that IL-1 may induce cellular responses by stimulating phosphoinositide turnover and possibly protein kinase C activity.

Arthritis, Rheumatoid↗