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Biomedical subjects

C Davis

Publications and source records attributed to C Davis.

At least 55 records · Page 3Linked to original sources
PubMed2000

Chronic exposure to bryostatin-1 increases the radiosensitivity of U937 leukaemia cells ectopically expressing Bcl-2 through a non-apoptotic mechanism.

PURPOSE: Ionizing radiation (IR) produced a dose-dependent increase in apoptosis in U937/pCEP4 cells which was attenuated by the stable over expression of Bcl-2 (U937/Bcl-2). A dose of 2 Gy IR was selected for further analyses to determine if subsequent exposure to 10nM bryostatin- would overcome the resistance to IR-induced apoptosis conferred by Bcl-2 over expression. METHODS AND RESULTS: Although bryostatin- did not increase IR-induced apoptosis in U937/pCEP4 or U937/Bcl-2 cells, it impaired mitochondrial function and increased the antiproliferative effects of IR in both cell lines. The effects were more pronounced in U937/Bcl-2 cells. Bryostatin-1 also exerted differential effects on cell-cycle distributions of U937 transfectant cells, producing a significant G0/G1 arrest in U937/Bcl-2 cells, while decreasing IR-induced G2/M arrest in U937/pCEP4 cells. Although Bcl-2 over expression attenuated IR-induced apoptosis, clonogenic survival was similar in U937/pCEP4 and U937/Bcl-2 cells following 2 Gy IR treatment. Treatment with 10nM bryostatin-1 after 2 Gy IR further reduced clonogenic survival in both cell lines. Moreover, U937/Bcl-2 cells were more susceptible to the growth-inhibitory effects of IR/bryostatin-1 than U937/pCEP4 cells. CONCLUSIONS: Bryostatin-1 increased the radiosensitivity of U937 transfectant cell lines without enhancing apoptosis; furthermore, U937/Bcl-2 cells were more susceptible to IR/bryostatin-1-mediated antiproliferative effects than their empty-vector counterparts.

Apoptosis↗
PubMed2000

Efficacy testing of recombinant human immunodeficiency virus (HIV) gp160 as a therapeutic vaccine in early-stage HIV-1-infected volunteers. rgp160 Phase II Vaccine Investigators.

A phase II efficacy trial was conducted with recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein gp160 (rgp160) in 608 HIV-infected, asymptomatic volunteers with CD4+ cell counts >400 cells/mm3. During a 5-year study, volunteers received a 6-shot primary series of immunizations with either rgp160 or placebo over 6 months, followed by booster immunizations every 2 months. Repeated vaccination with rgp160 was safe and persistently immunogenic. Adequate follow-up and acquisition of endpoints allowed for definitive interpretation of the trial results. There was no evidence that rgp160 has efficacy as a therapeutic vaccine in early-stage HIV infection, as measured at primary endpoints (50% decline in CD4+ cell count or disease progression to Walter Reed stage 4, 5, or 6) or secondary endpoints. A transient improvement was seen in the secondary CD4 endpoint for the vaccination compared with the placebo arm, but this did not translate into improved clinical outcome.

AIDS Vaccines↗
PubMed2000

8,9-dihydroxy-8,9-dihydrodibenzo[a,l]pyrene is a potent morphological cell-transforming agent in C3H10T(1)/(2)Cl8 mouse embryo fibroblasts in the absence of detectable stable covalent DNA adducts.

The comparative genotoxic effects of racemic trans-8,9-dihydroxy-8, 9-dihydrodibenzo[a,l]pyrene (trans-DB[a,l]P-8,9-diol), the metabolic K-region dihydrodiol of dibenzo[a,l] pyrene (DB[a,l]P) (dibenzo[def, p]chrysene) and DB[a,l]P in transformable mouse embryo C3H10T(1)/(2)Cl8 (C3H10T(1)/(2)) fibroblasts was investigated. The C3H10T(1)/(2) mouse embryo morphological cell-transforming activities of these polycyclic aromatic hydrocarbons (PAHs) were assayed using concentration-response studies. At concentrations of 33 nM and above both trans-DB[a,l]P-8,9-diol and DB[a,l]P produced significant (and similar) numbers of type II and III foci per dish and numbers of dishes with type II and II foci. Concomitant cytotoxicity studies revealed a reduction in colony survival of approximately 25% up to 198 nM for both PAHs. DNA adducts of trans-DB[a,l]P-8,9-diol and DB[a,l]P in C3H10T(1)/(2) cells were analyzed by a (32)P-post-labeling TLC/HPLC method. No adducts were observed in the DNA of C3H10T(1)/(2) cells treated with trans-DB[a, l]P-8,9-diol at concentrations that induced morphological cell transformation. Under the same exposure and chromatographic conditions, DNA adducts of deoxyadenosine and deoxyguanosine derived from the fjord region anti-DB[a,l]P-11,12-diol-13,14-epoxide and syn-DB[a,l]P-11,12-diol-13,14-epoxide were observed in the DNA of DB[a,l]P-treated cells. These results indicate that trans-DB[a,l]P-8, 9-diol has intrinsic genotoxic activity equal to that of DB[a,l]P, based on morphological cell transformation of mouse embryo fibroblasts. The activity of trans-DB[a,l]P-8,9-diol is apparently not associated with the formation of observable stable covalent DNA adducts. These results suggest that under appropriate conditions, trans-DB[a,l]P-8,9-diol may serve as an intermediate in the genotoxicity of DB[a,l]P.

Animals↗
PubMed2000

Adenoviral-mediated gene transfer to mouse salivary glands.

Adenoviral vectors effectively transfer genes to rat salivary glands. However, potent immune responses limit their use in vivo. Mice offer more opportunities than rats for the study of these immune processes. We first established conditions for infection of mouse salivary glands, with an adenoviral vector. The effects of time, viral dose, viral diluent buffer volume, and dexamethasone on expression of a transgene, luciferase, were determined by means of the recombinant vector AdCMVluc. Optimal luciferase expression was observed when the vector was suspended in 50 microL of buffer. This volume completely filled the gland parenchyma and slightly distended the capsule. Dexamethasone increased immediate transgene expression and reduced the acute inflammation one day following viral administration, but did not alter subsequent mononuclear inflammation or transgene expression 14 or 28 days later. An adenoviral vector encoding either anti-inflammatory cytokine IL-4 or IL-10 was co-administered with AdCMVluc to increase transgene expression at 14 and 28 days. While this strategy did not extend the duration of luciferase expression, co-administration of AdCMVIL-10 with AdCMVluc almost completely eliminated the chronic inflammatory infiltrate in the glands after 28 days. This study demonstrates that adenoviral-mediated gene transfer to mouse submandibular glands is possible by intraductal cannulation and that reduction of either the acute or chronic inflammatory infiltrates was insufficient to increase long-term transgene expression in this tissue.

Adenoviridae↗
PubMed1999

In vivo human metabolism of [2-14C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

To better understand the interactions of the pathways of activation and detoxification on the metabolism of the putative carcinogen, PhIP, we administered a dose of 70-84 microg [2-14C] PhIP (17.5 [microCi 14C) 48-72 h before scheduled colon surgery. Blood and urine collected for the next 48-72 h was evaluated by linear accelerator mass spectroscopy (AMS) and scintillation counting LC-MS to identify specific PhIP metabolites. The thermostable phenol sulfotransferase (SULT1A1) phenotype was correlated with the 4'-PhIP-SO4 levels in the urine at 0-4 h (R = 0.86, P = 0.059). The CYP1A2 activity had a negative correlation with PhIP serum levels at 1 h (R = 0.94, P = 0.06) and a positive correlation with urine N-OH-PhIP levels at 0-4 h (R = 0.85, P = 0.15). This low level radioisotope method of determining the influence of phenotype on metabolism will significantly improve our understanding of the interrelationships of these pathways and provide a critical foundation for the development of individual risk assessment.

Adult↗
PubMed1999

Molecular characterisation of cloned bradykinin B1 receptors from rat and human.

This report describes the characterisation of cloned rat and human bradykinin B1 receptors in African green monkey kidney fibroblast (Cos-7) cells. A ligand binding assay with [3H]des-Arg10-kallidin was used to compare their pharmacology with respect to known bradykinin B1 and B2 receptor ligands. In addition, the pharmacology of T-kinin and its' derivative des-Arg11-T-kinin was investigated. The cloned rat receptor had a similar pharmacology to that of the recently described mouse receptor and differs from that described for the human receptor. The rat receptor had a higher affinity for des-Arg11-T-kinin than the human receptor. These differences in pharmacological properties may relate to the presence of T-kinin, bradykinin and their des-Arg derivatives as the major physiological peptides in rat and the predominance of kallidin and its derivatives in human. We confirm that the rat bradykinin B1 receptor gene is organised in a two exon structure and differs from the human gene which has a three exon structure and we further examine the inducible expression of this gene in a wide range of tissues using Northern blotting.

Amino Acid Sequence↗
PubMed1999

Antibody-dependent cellular cytotoxicity in HIV type 1-infected patients receiving VaxSyn, a recombinant gp160 envelope vaccine.

Antibody-dependent cellular cytotoxicity (ADCC) activity was measured in 60 human immunodeficiency virus (HIV-1)-infected patients receiving a recombinant gp160 (rgp160) envelope protein of HIV-1(NL4-3) in alum and 64 receiving placebo over a 5-year study period. There was no difference in the percentage of ADCC responders when comparing rgp160-immunized patients (mean, 78.4%) with those receiving placebo alone (mean, 81.5%) at any time point examined. Patients were further divided into progression groups regardless of their vaccine status. ADCC activity was somewhat higher in rapid than in slow-progressing groups, although the number that had detectable ADCC activity was equivalent in each group. ADCC activity of sera from rapid- and slow-progressing groups against primary or laboratory isolate envelopes was similar. This study showed that transcription with rgp160 did not appear to enhance HIV-specific ADCC activity. ADCC activity did not appear to correlate with protection against AIDS in this cohort of HIV-1-infected people.

AIDS Vaccines↗
PubMed1999

Perfection as acculturation: psychological correlates of eating problems in Chinese male and female students living in the United States.

OBJECTIVE: The purpose of this study was to assess the relationship between acculturation, self-esteem, depression, and characteristics associated with eating disorders among Chinese university students in the United States. METHOD: A self-report questionnaire which included an acculturation scale (SL-ASIA), Center for Epidemiologic Studies of Depression (CES-D), Index of Self Esteem (ISE), and the Eating Disorders Inventory (EDI) was administered to 197 Chinese university students in the United States (93 females and 104 males). RESULTS: Highly acculturated females reported significantly higher EDI total scores, more maturity fears, and a greater sense of ineffectiveness. Males who were less acculturated also reported high ineffectiveness while high male scores on acculturation were associated with greater perfectionism. Overall, females reported more body dissatisfaction and drive for thinness, and respondents with high acculturation reported more perfectionism and interoceptive awareness. DISCUSSION: The impact of perfecting onself or one's body as a means of acculturating is discussed along with potential gender differences in perceived efficacy in a new culture.

Adolescent↗
PubMed1999

The use of automated data to identify complications and comorbidities of diabetes: a validation study.

We evaluated the accuracy of administrative data for identifying complications and comorbidities of diabetes using International Classification of Diseases, 9th edition, Clinical Modification and Current Procedural Terminology codes. The records of 471 randomly selected diabetic patients were reviewed for complications from January 1, 1993 to December 31, 1995; chart data served to validate automated data. The complications with the highest sensitivity determined by a diagnosis in the medical records identified within +/-60 days of the database date were myocardial infarction (95.2%); amputation (94.4%); ischemic heart disease (90.3%); stroke (91.2%); osteomyelitis (79.2%); and retinal detachment, vitreous hemorrhage, and vitrectomy (73.5%). With the exception of amputation (82.9%), positive predictive value was low when based on a diagnosis identified within +/-60 days of the database date but increased with relaxation of the time constraints to include confirmation of the condition at any time during 1993-1995: ulcers (88.5%); amputation (85.4%); and retinal detachment, vitreous hemorrhage and vitrectomy (79.8%). Automated data are useful for ascertaining potential cases of some diabetic complications but require confirmatory evidence when they are to be used for research purposes.

Adolescent↗
PubMed1999

A new sensor for monitoring chest wall motion during high-frequency oscillatory ventilation.

The recently developed technique of fibre optic respiratory plethysmography (FORP) has been modified to monitor the rapid, small amplitude movements of the chest wall during high-frequency oscillatory ventilation (HFOV). The FORP sensor is an expandable belt encircling the chest, in which is housed a fibre optic loop that alters its radius of curvature as a function of chest perimeter. These curvature changes cause variations in macrobending losses of light transmitted through the fibre, which are proportional to the chest perimeter. Dynamic measurement of transmitted light intensity can hence be used to monitor chest wall motion (CWM). For application to HFOV, the design of the FORP belt was altered to increase sensitivity and the materials were chosen to maximise macrobending effects induced by the CWM. FORP was tested in four piglets ventilated with HFOV, both in the normal and surfactant-deficient lung. Measurement of CWM was possible over the full range of tidal volumes and ventilation frequencies used during HFOV. In all cases, the measured frequency of the CWM fell within 3% of the applied ventilation frequency. In addition, the technique was sufficiently sensitive to detect changes in the amplitude of CWM in response to changes in applied tidal volume. It is anticipated that application of this new non-invasive measurement device will lead to an increased understanding of the dynamics of chest and abdominal wall motion during HFOV.

Animals↗
PubMed1999

Epitope-specific glutamic acid decarboxylase-65 autoantibodies in intravenous immunoglobulin preparations.

Intravenous immunoglobulin (IVIG) has been used to treat many autoimmune disorders including Stiff-Man Syndrome (SMS). SMS is a neurological disorder associated with an immune-mediated deficiency of gamma-aminobutyric acid (GABA) due to autoantibodies against the GABA synthesizing enzyme glutamic acid decarboxylase-65 (GAD65). GAD65 autoantibodies are present among 1-2% of healthy individuals. It can therefore not be excluded that GAD65 autoantibodies may be present in IVIG, which is prepared from multiple blood donors. We report here that GAD65 but not IA-2 autoantibodies were present in commercial IVIG preparations. The presence of autoantibodies may affect the outcome of IVIG treatment and screening commercial preparations of IVIG for GAD65 autoantibodies is therefore recommended before treating patients.

Antibody Affinity↗
PubMed1999

Repeated immunization with recombinant gp160 human immunodeficiency virus (HIV) envelope protein in early HIV-1 infection: evaluation of the T cell proliferative response.

This longitudinal study was designed to evaluate cellular immunity in early-stage, asymptomatic human immunodeficiency virus (HIV)-1-infected persons (CD4 cell count,>400/mm3; median, 625/mm3) who were immunized with either recombinant (r) gp160 or placebo every 2 months for 5 years. Proliferative responses were assessed against rgp160, rp24, and a panel of recall antigens and mitogens. Despite good reactivity to recall antigens, at baseline approximately 33% had proliferative responses to gp160, and approximately 42% showed p24 gag responses. There was no statistical difference between vaccine and placebo groups for antigens or mitogens. After 1 year, approximately 73% of the subjects in the vaccine arm had new or boosted responses to gp160, versus approximately 18% in the placebo arm. Statistical significance was maintained throughout the study. Recurrent vaccination with recombinant gp160 was proven to be persistently immunogenic, increasing significantly the ability of HIV-1-infected persons to mount new proliferative responses to the vaccine.

AIDS Vaccines↗
PubMed1999

The identification of [2-(14)C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine metabolites in humans.

[2-(14)C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ([14C]PhIP), a putative human carcinogenic heterocyclic amine found in well-done cooked meat, was administered orally to three colon cancer patients undergoing a partial colonectomy. Forty-eight to seventy-two hours prior to surgery, subjects received a 70-84 microg dose of 14C. Urine and blood were analyzed by HPLC for PhIP and PhIP metabolites. Metabolites were identified based on HPLC co-elution with authentic PhIP metabolite standards, mass spectral analysis and susceptibility to enzymatic cleavage. In two subjects, approximately 90% of the administered [14C]PhIP dose was eliminated in the urine, whereas in the other, only 50% of the dose was found in the urine. One subject excreted three times more radioactivity in the first 4 h than did the others. Twelve radioactive peaks associated with PhIP were detected in the urine samples. The relative amount of each metabolite varied by subject, and the amounts of each metabolite within subjects changed over time. In all three subjects the most abundant urinary metabolite was identified as 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine-N2-glucuron ide (N-hydroxy-PhIP-N2-glucuronide), accounting for 47-60% of the recovered counts in 24 h. PhIP accounted for <1% of the excreted radiolabel in all three patients. Other metabolites detected in the urine at significant amounts were 4-(2-amino-1-methylimidazo[4,5-b]pyrid-6-yl)phenyl sulfate, N-hydroxy-PhIP-N3-glucuronide and PhIP-N2-glucuronide. In the plasma, N-hydroxy-PhIP-N2-glucuronide accounted for 60, 18 and 20% of the recovered plasma radioactivity at 1 h post PhIP dose in subjects 1, 2 and 3 respectively. Plasma PhIP was 56-17% of the recovered dose at 1 h post exposure. The relatively high concentration of N-hydroxy-PhIP-N2-glucuronide and the fact that it is an indicator of bioactivation make this metabolite a potential biomarker for PhIP exposure and activation. Determining the relative differences in PhIP metabolites among individuals will indicate metabolic differences that may predict individual susceptibility to carcinogenic risk from this suspected dietary carcinogen.

Administration, Oral↗
PubMed1999

Targeted inactivation of Dp71, the major non-muscle product of the DMD gene: differential activity of the Dp71 promoter during development.

The dystrophin gene, which is defective in Duchenne muscular dystrophy (DMD), also encodes a number of smaller products controlled by internal promoters. Dp71, which consists of the two C-terminal domains of dystrophin, is the most abundant product of the gene in non-muscle tissues and is the major product in adult brain. To study the possible function of Dp71 and its expression during development, we specifically inactivated the expression of Dp71 by replacing its first and unique exon and a part of the concomitant intron with a beta-galactosidase reporter gene. X-Gal staining of Dp71-null mouse embryos and tissues revealed a very stage- and cell type-specific activity of the Dp71 promoter during development and during differentiation of various tissues, including the nervous system, eyes, limb buds, lungs, blood vessels, vibrissae and hair follicles. High activity of the Dp71 promoter often seemed to be associated with morphogenic events and terminal differentiation. In some tissues the activity greatly increased towards birth.

Animals↗