Search PubMed⌕ Search

Biomedical subjects

J R Davis

Publications and source records attributed to J R Davis.

At least 91 records · Page 5Linked to original sources

Effects of para-aminobenzoic acid, insulin, and gentamicin on Plasmodium falciparum development in anopheline mosquitoes (Diptera: Culicidae).

Anopheles gambiae Giles sensu lato (s.l.) and An. stephensi Liston were exposed as adults to para-aminobenzoic acid (PABA), human insulin, or gentamicin sulfate, an antimicrobial solution, to determine their effects on Plasmodium falciparum Welch development to the oocyst stage. For both mosquito species, concentrations of PABA from 0.001 to 0.05% had no effect on either oocyst infection rates or oocyst densities. At higher concentrations, PABA-fed mosquitoes had decreased oocyst infection rates when they were exposed after, but not before, experimental infections. Insulin-fed mosquitoes had significantly higher oocyst infection rates than controls and increased oocyst densities in both An. gambiae s.l and An. stephensi. The most dramatic impact on parasite development was observed for mosquitoes fed on gentamicin. For An. gambiae s.l. fed 0.05% gentamicin, oocyst infection rates were 3.7-fold higher than in controls, whereas oocyst densities were 5.7 times greater than in controls. Anopheles stephensi fed on diets of 0.1% gentamicin had 2.4-fold higher infection rates and increased oocyst densities. Concentrations of gentamicin above 0.1% had deleterious effects on mosquito survival and their ability to digest blood meals. These findings provide insight into how antibiotics, hormones, and metabolites may affect the development of P. falciparum in An. gambiae s.l. and An. stephensi.

4-Aminobenzoic Acid↗

Human small cell lung cancer cell lines expressing the proopiomelanocortin gene have aberrant glucocorticoid receptor function.

Some human small cell lung carcinomas (SCLC) secrete proopiomelanocortin (POMC) derived peptides, but in contrast to the pituitary, glucocorticoids fail to inhibit this hormone production. We have previously described an in vitro model using human SCLC cell lines that express POMC and are resistant to glucocorticoids. We have now identified the glucocorticoid receptor (GR) in the SCLC cell line COR L24 using a whole cell ligand binding assay (Kd = 5.7 nM; Bmax = 11 fmol/million cells), while another cell line, DMS 79, lacked significant glucocorticoid binding. To analyze GR function both positive (GMCO) and negative (TRE)3-tkCAT), glucocorticoid-regulated reporter gene constructs were transfected into COR L24 cells. In the SCLC cell line, neither hydrocortisone nor dexamethasone (500-2,000 nM) significantly induced chloramphenicol acetyltransferase expression from GMCO; in addition, they did not suppress chloramphenicol acetyltransferase expression from (TRE)3-tkCAT. Similar results were obtained with two other POMC-expressing SCLC cell lines. Expression of wild type GR in COR L24 cells restored glucocorticoid signaling, with marked induction of GMCO reporter gene expression by dexamethasone (9,100 +/- 910%; n = 3), and an estimated EC50 of 10 nM. This failure of the GR explains the resistance of the POMC gene to glucocorticoid inhibition and may have implications for cell growth in SCLC.

Carcinoma, Small Cell↗

Characterization of an up-stream promoter directing extrapituitary expression of the human prolactin gene.

The human PRL gene is expressed outside pituitary lactotrophs in decidualized endometrium and lymphoid cells, but here the mRNA contains a 5'-untranslated region from an additional noncoding exon 1a. We have isolated a genomic DNA clone containing human PRL exon 1a with 2800 basepairs (bp) of 5'-flanking sequences. Sequencing locates exon 1a -5840 bp up-stream of the pituitary start site. To study its suspected regulatory function, various lengths of the 5'-flanking region were linked to the luciferase (Luc) reporter gene. Their ability to direct gene expression has been analyzed in transfection studies. The proximal 1620 bp of promoter sequence directed Luc expression in the T-lymphoid Jurkat cell line, and this was unaffected by 5'-deletion to the proximal 453 bp. However, further 5'-deletion to the most proximal 67 bp drastically reduced this activity by 90%. The exon 1a promoter was inactive in pituitary GH3 cells and HeLa cells; in contrast, the exon 1b pituitary promoter, active in GH3 cells, was inactive in Jurkat cells. DNase-I footprinting studies and further 5'- and 3'-deletion analysis identified factor-binding sites within an enhancer element located at -375/-212 bp, which contributed approximately 50% of the promoter activity.

Animals↗

Natural and structured baselines in the treatment of aggression following brain injury.

This single-case study describes the importance of presenting relevant baseline conditions in planning and evaluating treatment for aggression in a severely brain injured man 1 year after injury. An artificially low natural baseline resulted from staff reluctance to deliver instructions and corrective feedback needed for rehabilitation of self-care skill because these were frequently followed by aggression. A subsequent structured baseline presented these antecedents at the higher rates that were necessary for progress in the patient's rehabilitation. This resulted in an increase in aggressive behaviour, but also gave a more accurate representation of what his behaviour would be like under effective rehabilitation conditions. Intervention was based on data from the structured baseline, and included providing clear expectations, social reinforcement, and decelerative procedures. After reduction of aggression to zero, regular staff were reintroduced and presented instruction and corrective feedback as required. No further aggressive behaviour was noted, and self-care improved so that only minimal assistance was needed. Six months following reintroduction of regular staff, both baseline conditions were replicated. No aggressive behaviour was observed during either, suggesting that maintenance of gains could not be attributed to an artificially reduced rate caused by staff avoiding trigger antecedents.

Aggression↗

Aviation medicine.

Explore the source record for details and available documents.

Aerospace Medicine↗

Mechanical distraction for treatment of severe knee flexion contractures.

Ten patients (14 knees) with severe knee flexion contractures were treated by gradual mechanical distraction using either the Ilizarov or Orthofix external fixator. Range of motion improved from an average flexion contracture of 60 degrees before surgery to 16 degrees at the follow-up evaluation. Range of motion results were graded good or excellent in five knees, fair in two knees, and poor in three knees. Average total arc of motion remained essentially unchanged when comparing the preoperative (59 degrees) with the follow-up results (63 degrees). However, the functional position of this arc improved significantly. Problems encountered included a "rebound" phenomena after frame removal, with loss of the temporarily increased total arc of motion. The role of hamstring tenotomy and radical posterior knee release remains unclear.

Adolescent↗

Evaluation of families wherein a single male manifests a phenotype of X-linked lymphoproliferative disease (XLP).

The Epstein-Barr virus (EBV)-induced diseases of males with X-linked lymphoproliferative disease (XLP) include fatal infectious mononucleosis (IM), non-Hodgkin lymphoma (ML), agammaglobulinemia, and aplastic anemia. These phenotypes also occur as sporadic cases in families, and EBV seronegative males in these families must be considered at risk for XLP until they seroconvert normally to EBV. Given that 50% of males inheriting the defective XLP gene die following primary EBV infection, it is vital that they be identified pre-EBV infection. Here we report results using molecular genetic techniques to provide information as to the relative risks of EBV negative males and potential carrier females in ten families wherein a single male had died of IM.

Adolescent↗

Plasmodium falciparum: inhibition of sporogonic development in Anopheles stephensi by gram-negative bacteria.

We investigated the effects of bacteria on Plasmodium falciparum sporogonic development in Anopheles stephensi. Four gram-negative (Escherichia coli H243, E. coli HB101, Pseudomonas aeruginosa, and Ewingella americana) and two gram-positive (Staphylococcus aureus and Staphylococcus epidermidis) bacterial strains were used in the study. Tenfold dilutions of bacteria suspended in phosphate-buffered saline were mixed with an infectious meal of gametocyte-enriched cultures and fed to adult mosquitoes. All gram-negative bacteria strains partially or completely inhibited oocyst formation at different concentrations. Additionally, geometric mean number of oocysts showed a correspondingly significant decrease with increasing bacterial concentration (P < 0.001). In contrast, gram-positive bacteria strains did not have any inhibitory effects on oocyst formation even at very high concentrations. Oocyst development was not affected by: (i) culture supernatants of E. americana, (ii) formalin-treated E. coli H243, (iii) lipopolysaccharide of E. coli J5 (mutant of 0111:B4). These studies show that gram-negative but not gram-positive bacteria affect sporogonic-stage development of P. falciparum in A. stephensi. Inhibition of parasite acquisition may be an attribute of specific or nonspecific cytoadherence properties of gram-negative bacteria to the parasites.

Animals↗

Human performance and physiological function during a 24-hr exposure to 1% bromotrifluoromethane (Halon 1301).

Performance and physiological measurements were obtained from four pairs of men exposed for 24 hr to 1% (10,000 ppm) Halon 1301 (bromotrifluoromethane, CBrF3) and to air with order counterbalanced using a double-blind protocol. Cognitive and motor performance was assessed before, during, and after the exposures using seven scales of the Automated Portable Testing System, which produced 13 measures of performance. Halon inhalation induced decrements in 2 of the 13 measures, but actual and estimated magnitudes of the decrements were no greater than 5% of baseline values. Physiological data were obtained before, during, and after the exposures from clinical chemistry analyses of blood and urine samples, pulmonary function tests, and monitoring of vital signs. Significant change during Halon inhalation was observed for 6 of the 52 variables assessed; however, all physiological values remained within clinically acceptable limits. No cardiovascular effects were noted. This study demonstrated that exposure to 1% Halon 1301 for 24 hr can produce minor disturbance of central nervous system function as assessed by cognitive tasks.

Administration, Inhalation↗

Family pesticide use and childhood brain cancer.

The relationship between family pesticide use and childhood brain cancer was examined in a case-control study. Telephone interviews were conducted from June 1989 through March 1990 with the natural mothers of 45 childhood brain cancer cases, 85 friend controls, and 108 cancer controls. In comparisons to friend controls, significant positive associations were observed for use of pesticides to control nuisance pests in the home, no-pest-strips in the home, pesticides to control termites, Kwell shampoo, flea collars on pets, diazinon in the garden or orchard, and herbicides to control weeds in the yard. In comparisons to cancer controls, significant positive associations were observed for use of pesticide bombs in the home, pesticides to control termites, flea collars on pets, insecticides in the garden or orchard, carbaryl in the garden or orchard, and herbicides to control weeds in the yard. In general, positive associations in comparisons to one control group were supported by elevated odds ratios in comparisons to the other control group. Several potentially important associations were identified in this study. However, small sample sizes, potential recall bias, multiple comparisons, and lack of detailed exposure verification require further research to confirm these findings.

Brain Neoplasms↗

Comparison of treatment strategies for Space Motion Sickness.

Treatment strategies for Space Motion Sickness (SMS) were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of SMS were graded as mild, moderate, or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through Private Medical Conferences with the crew. A symptom matrix was analyzed for 19 crewmembers treated with oral combination of scopolamine and dextroamphetamine (scopdex) and 15 crewmembers treated with promethazine delivered by intramuscular i.m. or suppository routes. Scopdex has been given preflight as prophylaxis for SMS, but analysis showed delayed symptom presentation in 9 crewmembers or failed to prevent symptoms in 7. Only 3 crewmembers who took scopdex had no symptoms inflight. Fourteen out of 15 crewmembers treated with i.m. promethazine and 6 of 8 treated with promethazine suppositories after symptom development had immediate (within 1-2 h) symptom relief and required no additional medication. There were no cases of delayed symptom presentation in the crewmembers treated with promethazine. This response is in contrast to untreated crewmembers who typically have slow symptom resolution over 72-96 h. We conclude that promethazine is an effective treatment of SMS symptoms inflight. NASA policy currently recommends treating crewmembers with SMS after symptom development, and no longer recommends prophylaxis with scopdex due to delayed symptom development and apparent variable absorption of oral medications during early flight days.

Aerospace Medicine↗

Thyrotropin-releasing hormone and epidermal growth factor induce human prolactin expression via identical multiple cis elements.

Pituitary GH3 cells were transfected with different deletion mutants of the human prolactin (hPRL) promoter fused to the CAT reporter gene. The proximal region (-250 to -42) was sufficient to confer stimulation by both thyrotropin-releasing hormone (TRH) and epidermal growth factor (EGF). Further deletion analyses demonstrated the importance of the three proximal Pit-1 binding sites in this response. However, Pit-1 binding oligonucleotides confer neither TRH nor EGF induction to a linked neutral promoter, suggesting that other elements might be involved. We have previously shown that sequence A (-115 to -85) is needed together with Pit-1 binding sites for full cyclic AMP response of hPRL-CAT. Mutation of this sequence strongly affects TRH and EGF induction. On the other hand, three copies of sequence A confer both TRH and EGF response to a linked neutral promoter. In conclusion, although TRH and EGF activate mostly different intracellular pathways, they mediate transcriptional induction of the hPRL promoter via identical cis elements.

Animals↗

Coping modeling problem solving versus mastery modeling: effects on adherence, in-session process, and skill acquisition in a residential parent-training program.

This trial compared two approaches used to introduce parenting skills in a residential staff training program. Fifty staff were randomly assigned to: mastery modelling in which videotaped models demonstrated new skills, coping modelling problem solving (CMPS) in which participants formulated their own solutions to the errors depicted by videotaped models, or a waiting-list control group. In both, leaders used modelling, role playing, and homework projects to promote mastery and transfer of new skills. The skills of all groups improved, but CMPS participants attended more sessions, were late to fewer sessions, completed more homework, engaged in more cooperative in-session interaction, rated the program more positively, and reported higher job accomplishment scores. These data suggest that CMPS allowing participants to formulate their own solutions may enhance adherence and reduce the resistance observed in more didactic programs.

Adaptation, Psychological↗

Cancer control knowledge and priorities among primary care physicians.

Primary care physicians can play a key role in prevention and early detection of cancer. To assess cancer control knowledge and priorities among primary care physicians in Missouri, we conducted a random survey of 207 physicians. Although reported knowledge of the role tobacco plays in cancer causation was high, activity in tobacco cessation counselling and referral was low. Respondents considered diet to be a relatively unimportant factor in cancer causation, whereas they viewed sun exposure, genetics/family history, and radiation exposure as large contributors to the cancer burden. Among cancer early detection tests, high activity was shown for the Pap test and breast examination. Conversely, low activity was reported for colon sigmoidoscopy. Inverse correlations were shown between age group of the physician and several cancer prevention and early detection practices. For each cancer prevention and screening practice, reported activity was higher for medical doctors than for doctors of osteopathic medicine. Possible barriers or controversies in cancer control included disagreement with the current recommendation for Pap testing, the cost of mammography, and patient fear of sigmoidoscopy. These findings suggest that primary care physicians are not achieving their full potential in cancer control and indicate areas where increased emphasis is warranted.

Attitude of Health Personnel↗

Long-term persistence of sterile immunity in a volunteer immunized with X-irradiated Plasmodium falciparum sporozoites.

Three volunteers were immunized by repeated exposure to the bites of Plasmodium falciparum-infected, X-irradiated mosquitoes to characterize immunologic responses and duration of protective immunity. A primary series of immunizations had been shown previously to induce sterile immunity in these volunteers against sporozoite-induced P. falciparum malaria. In the current study, antibodies to sporozoites circulated at high levels for at least 9-12 months after the volunteers were administered booster bites from X-irradiated infective mosquitoes. One volunteer challenged a second time with P. falciparum 9 months after his last immunization was again shown to be protected, whereas all 5 control subjects developed patent infections. These results set a new standard for persistence of sterile immunity against experimental P. falciparum infection.

Adult↗

Glucocorticoid inhibition of ACTH peptides: small cell lung cancer cell lines are more resistant than pituitary corticotroph adenoma cells.

In the normal pituitary, glucocorticoids are the principal negative regulatory of the pro-opiomelanocortin (POMC) gene which gives rise to the biologically active peptides ACTH and beta-endorphin. In Cushing's syndrome, ACTH-secreting pituitary tumours show a degree of glucocorticoid resistance, whilst ACTH-secreting extra-pituitary tumours have an even greater resistance to glucocorticoid excess. In an attempt to understand the mechanism of this phenomenon, we have compared the effects of glucocorticoids on POMC mRNA and peptide secretion in human and mouse corticotroph adenoma cells and in small cell lung carcinoma (SCLC) cells. ACTH precursor peptides were inhibited within 24 h by 25-50 nM hydrocortisone in primary cultures from a human corticotroph adenoma. In the mouse corticotroph adenoma cell line (AtT20), inhibition of both ACTH precursors and ACTH was not observed after 24 h but, by 10 days, glucocorticoids suppressed peptide levels with a concentration causing 50% inhibition of 50 nM hydrocortisone and maximal inhibition at 500 nM hydrocortisone. In marked contrast, there was no response to 500 nM hydrocortisone in the five SCLC cell lines (COR L103, COR L42, COR L24, COR L31, DMS 79) all of which secrete ACTH precursors. However, two of the five SCLC cell lines (COR L31 and DMS 79) were responsive to 1000 nM hydrocortisone. POMC mRNA, quantitated by slot-blot analysis, gave similar results for the five SCLC cell lines, implying that the abnormality may occur at the level of gene expression. When one of the three resistant cell lines (COR L103) was incubated with 2000 nM hydrocortisone or 2000 nM dexamethasone a clear suppression of precursor peptides and POMC mRNA was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗