Biomedical subjects

J G Turner

Publications and source records attributed to J G Turner.

At least 19 recordsLinked to original sources

PubMed2001

Broad-spectrum mildew resistance in Arabidopsis thaliana mediated by RPW8.

Plant disease resistance (R) genes control the recognition of specific pathogens and activate subsequent defense responses. We show that the Arabidopsis thaliana locus RESISTANCE TO POWDERY MILDEW8 (RPW8) contains two naturally polymorphic, dominant R genes, RPW8.1 and RPW8.2, which individually control resistance to a broad range of powdery mildew pathogens. Although the predicted RPW8.1 and RPW8.2 proteins are different from the previously characterized R proteins, they induce localized, salicylic acid-dependent defenses similar to those induced by R genes that control specific resistance. Apparently, broad-spectrum resistance mediated by RPW8 uses the same mechanisms as specific resistance.

Alleles↗

PubMed2001

Anti-CD40 antibody induces antitumor and antimetastatic effects: the role of NK cells.

We assessed the effect of the stimulatory anti-CD40 Ab on NK cell activation in vivo and the therapeutic potential of activated NK cells in tumor-bearing mice. Single-dose i.p. injection of the anti-CD40 Ab resulted in production of IL-12 and IFN-gamma in vivo, followed by a dramatic increase in NK cell cytolytic activity in PBLs. NK cell activation by anti-CD40 Ab was also observed in CD40 ligand knockout mice. Because NK cells express CD40 ligand but not CD40, our results suggest that NK activation is mediated by increased cytokine production upon CD40 ligation of APCs. Treatment of tumor-bearing mice with anti-CD40 Ab resulted in substantial antitumor and antimetastatic effects in three tumor models. Depletion of NK cells with anti-asialo GM1 Ab reduced or abrogated the observed antitumor effects in all the tested models. These results indicate that a stimulatory CD40 Ab indirectly activates NK cells, which can produce significant antitumor and antimetastatic effects.

Animals↗

PubMed2001

The Arabidopsis mutant cev1 has constitutively active jasmonate and ethylene signal pathways and enhanced resistance to pathogens.

Jasmonates (JAs) inhibit plant growth and induce plant defense responses. To define genes in the Arabidopsis JA signal pathway, we screened for mutants with constitutive expression of a luciferase reporter for the JA-responsive promoter from the vegetative storage protein gene VSP1. One mutant, named constitutive expression of VSP1 (cev1), produced plants that were smaller than wild type, had stunted roots with long root hairs, accumulated anthocyanin, had constitutive expression of the defense-related genes VSP1, VSP2, Thi2.1, PDF1.2, and CHI-B, and had enhanced resistance to powdery mildew diseases. Genetic evidence indicated that the cev1 phenotype required both COI1, an essential component of the JA signal pathway, and ETR1, which encodes the ethylene receptor. We conclude that cev1 stimulates both the JA and the ethylene signal pathways and that CEV1 regulates an early step in an Arabidopsis defense pathway.

Arabidopsis↗

PubMed2000

Effects of diary food supplements on bone mineral density in teenage girls.

BACKGROUND: Bone mineral density (BMD) is largely genetically determined and this influence is most powerful in the period of rapid skeletal development in childhood and late adolescence but environmental factors such as exercise and dietary calcium intake may influence up to 20%. AIMS OF THE STUDY: The aims of the study were to examine healthy late adolescent females for the effects and benefits of a high calcium intake from dairy product foods on bone mineral density, body composition, lipids and biochemistry. The secondary aim is determine whether a high intake of dairy product foods in the diet is acceptable for this age group long term. METHODS: Ninety-one teenage girls who participated in a two-year randomised controlled study on the effect of dairy food supplementation on dietary patterns, body composition and bone density in post-pubertal teenage girls were approached one year after the cessation of the study to determine the effects of the cessation of dairy supplements on bone mineral density, dietary habits, biochemical markers, body composition and blood lipids. Bone mineral density and bone mineral content were assessed at the hip, spine and total body. Anthropometric data were collected, and exercise, Tanner, dietary assessment, preference and compliance questionnaires were administered. Lipid profiles, hydroxyproline excretion and urinary calcium and sodium excretion measurements were performed. RESULTS: There were no significant differences between the 2 groups for height, weight, lean and fat mass. The supplemented group had significantly higher calcium, phosphorus and protein intake during the supplementation period (p < 0.001). No differences were seen between the groups 12 months after supplementation finished. There were no significant differences in exercise level, preference or acceptability of dairy products or in the lipids and bone markers between baseline the end of supplementation and 1 year follow-up. There was a significant increase in trochanter (4.6%), lumbar spine (1.5%) and femoral neck (4.8%) BMD (p < 0.05) in the high calcium group at the end of supplementation. There was an increase in bone mineral content at the trochanter (p < 0.05) and lumbar spine; however the latter was not statistically significant, in the high calcium group at the end of supplementation. There was no difference in vertebral height or width at any stage of the study, indicating no influence on bone size. CONCLUSIONS: In this 3 year study (2 years of supplementation, 1 year follow-up), teenage girls, aged 15-18 years, were able to significantly increase their BMD at the trochanter, femoral neck and lumbar spine when supplemented with dairy product foods to a mean calcium intake of 1160 mg/d. There was also an effect seen on the BMC particularly at the trochanter and to a lesser extent at the lumbar spine. The dietary calcium intake achieved did not adversely affect body weight, fat and lean mass or blood lipid profiles. Twelve months after the supplementation finished the girls had returned to their baseline diet, indicating self-selection of a high dairy product diet may be hard to achieve.

Adolescent↗

PubMed2000

Effects of exposure to an augmented acoustic environment on auditory function in mice: roles of hearing loss and age during treatment.

The effects of exposure to an augmented acoustic environment (AAE) on auditory function were evaluated in mouse strains that exhibit various degrees and time courses of progressive hearing loss (BXD-22, BXD-12, BXD-16, BXD-14, BALB/cJ), and in normal-hearing CBA/CaJ mice. Beginning at age 25 days, mice were exposed 12 h every night to a 70 dB SPL broadband noise AAE. The AAE was maintained for at least 30 days in each strain. Same-strain control mice were age-matched and maintained under normal vivarium acoustic conditions. The auditory brainstem response (ABR), acoustic startle response amplitude, and prepulse inhibition (PPI) were used to assess the auditory system. Exposure to the AAE resulted in improved auditory performance (better PPI, lower ABR thresholds) when hearing impairment was present, but not when hearing was normal. The ameliorative effects occurred irrespective of a mouse's age at the onset of hearing loss, as long as initiation of AAE treatment preceded the occurrence of severe hearing loss. If AAE treatment was delayed beyond such a point, loss of threshold sensitivity progressed as usual, although PPI could still benefit. Finally, AAE treatment can slow, but not prevent, the occurrence of severe genetically determined hearing loss.

Acoustic Stimulation↗

PubMed2000

Neural plasticity in the mouse inferior colliculus: relationship to hearing loss, augmented acoustic stimulation, and prepulse inhibition.

C57BL/6J (C57) and DBA/2J (DBA) mice exhibit progressive high-frequency hearing loss. Extracellular recordings of responses of neurons in the inferior colliculus (IC) evoked by 70-dB SPL tones indicated that normal tonotopic organization was greatly disrupted in both strains: still-audible lower frequencies (4-12 kHz) evoked responses in a large percentage of recording sites in ventral tonotopic regions that normally respond strongly to high frequencies only. To relate the IC responses to an auditory behavior, prepulse inhibition (PPI) was measured using 70-dB tones as prepulses. As high-frequency hearing loss progressed in C57 mice, prepulses of 4-12 kHz elicited stronger PPI, and this was significantly correlated with changes in the percentage of IC recording sites responding to 70-dB tones (the neural pathway for PPI includes the IC). The analysis was extended to DBA mice that had been exposed to an augmented acoustic environment (AAE) - a procedure that improves PPI. In these mice, a higher percentage of IC recording sites responded to 70-dB tones, and this was correlated with improved PPI. The data suggest that responses of IC neurons reflect both hearing loss-induced plasticity and changes induced by exposure to an AAE, and these neural changes are correlated with the magnitude of PPI.

Acoustic Stimulation↗

PubMed2000

Purkinje cell degeneration and control mice: responses of single units in the dorsal cochlear nucleus and the acoustic startle response.

The cartwheel cell is the most numerous inhibitory interneuron of the dorsal cochlear nucleus (DCN). It is expected to be an important determinant of DCN function. To assess the contribution of the cartwheel cell, we examined the discharge characteristics of DCN neurons and behavioral measures in the Purkinje cell degeneration (pcd) mice, which lack cartwheel cells, and compared them to those of the control mice. Distortion product otoacoustic emissions and auditory brainstem-evoked response thresholds were similar between the two groups. Extracellularly recorded DCN single units in ketamine/xylazine-anesthetized mice were classified according to post-stimulus time histogram (PSTH) and excitatory-inhibitory response area (EI-area) schemes. PSTHs recorded in mouse DCN included chopper, pauser/buildup, onset, inhibited and nondescript types. EI-areas recorded included Types I, II, III, I/III, IV and V. There were no significant differences in the proportions of various unit types between the pcd and control mice. The pcd units had slightly lower thresholds to characteristic frequency tones; however, they had spontaneous rates, thresholds to noise, and maximum driven rates to noise that were similar to those of the control units. Pcd mice had smaller startle amplitudes, but startle latency, prepulse inhibition/augmentation and facilitation by a background tone were comparable between the two groups. From these results, we conclude that DCN function in response to relatively simple acoustic stimuli is minimally affected by the absence of the cartwheel cells. Future studies employing more complex and/or multimodal stimuli should help assess the role of the cartwheel cells.

Acoustic Stimulation↗

PubMed2000

Fear-potentiated startle, but not prepulse inhibition of startle, is impaired in CREBalphadelta-/- mutant mice.

Fear-potentiated startle was assessed in mice with a targeted disruption of the alpha and delta isoforms of the transcription factor cAMP response element binding protein (CREB) 24 hr after 5 tone + shock training trials. Whereas wild-type mice showed fear-potentiated startle that persisted up to 45 days after training, CREBalphadelta-/- mice failed to show fear-potentiated startle. However, CREBalphadelta-/- and wild-type mice had similar startle amplitudes and similar magnitudes of prepulse inhibition of startle, suggesting that CREBalphadelta-/- mice have no obvious sensory or motor deficits. These results add to the literature indicating that CREB-activated transcription plays a critical role in the formation of long-term memory and illustrate the utility of the fear-potentiated startle paradigm for assessing cognition in genetically altered mice.

Animals↗

PubMed2000

Outcome of primary vesicoureteric reflux detected following fetal renal pelvic dilatation.

OBJECTIVE: Postnatal investigation of mild degrees of fetal hydronephrosis has allowed subsequent detection of infants with vesicoureteric reflux (VUR). This study was designed to provide short to medium term information on such infants who had primary VUR, the rates of renal damage and progression over time, the risk factors for such damage and to compare the characteristics of those who had mild dilatation of the fetal renal pelvis (4-9 mm) with those who had moderate-severe dilatation (> or = 10 mm). METHODOLOGY: Since June 1989, infants whose antenatal sonography had identified a fetal renal pelvis with an anteroposterior diameter of > 4 mm were investigated postnatally with renal ultrasonography and micturating cystourethrogram (MCU), and placed on antimicrobial prophylaxis. Those with VUR received 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy. Infants were followed until discharge based on resolution of VUR, surgery, or low grade VUR. A 5.5 year cohort between June 1989 and December 1994 formed the study population. A review of notes and clinical review (if still under follow up) was undertaken. Vesicoureteric reflux on MCU was regraded according to the International Classification, and reflux nephropathy on DMSA scans was regraded according to criteria proposed by Goldraich. Regression analysis was used to assess risk factors for renal damage. RESULTS: There were 69 infants (37 girls, 32 boys) who were identified with primary VUR, with 37/69 having bilateral reflux. Eight had a urinary tract infection during the follow-up period. There was a broad distribution of grades of reflux detected (Grades I-3, Grades II-23, Grades III-19, Grades IV - 17, Grades V-7). 99m-Tc-dimercaptosuccinic acid scans on 57/69 (83%) demonstrated renal damage in eight infants (14%). This was predominantly global contraction of function. No progression of renal damage was seen over 2-7 years. Regression analysis showed a strong association between Grades IV, V reflux and the presence of renal damage (P < 0.001). Review of the degrees of fetal renal pelvic dilatation showed that 60/69 infants were detected because of mild (4-9 mm) dilatation. The majority (43/60) had lower grades of reflux (Grades I, II, 3), but there was no obvious cut-off between 4 and 9 mm that could predict high grade VUR (Grades IV, V). CONCLUSIONS: The use of 4 mm to define an abnormal fetal renal pelvis allows a much larger group of infants with high grade primary VUR to be detected than if a higher cut-off measurement is used. Although it also detects many more infants with low grade primary VUR, there is no obvious cut-off point at which this effect predominates. Progressive renal damage was not seen in follow up of up to 7 years of age. Renal damage on DMSA scanning in this group is almost exclusively a pattern of global contraction of function. The presence of high-grade VUR appears to be the only important factor in predicting the presence of renal damage.

Child↗

PubMed2000

Monitoring of renal function in patients with spinal cord injury.

OBJECTIVE: To assess the sensitivity of serum creatinine level in detecting clinically important and early deterioration of renal function in patients with spinal cord injury (SCI), and to evaluate the optimal method of determining creatinine clearance in these patients. PATIENTS AND METHODS: The serum creatinine level of 36 patients (25 paraplegics and 11 quadriplegics) was evaluated and compared with the corresponding measured creatinine clearance rate. Correlations were also assessed between the creatinine clearance measured by 24-h endogenous clearance, single-shot 99mTc-labelled diethylenetriamine pentaacetic acid (99mTc-DTPA) clearance technique, and the Cockcroft-Gault formula, to test their validity. RESULTS: Of the 36 patients 11 (31%) had a measured creatinine clearance of < 100 mL/min (mean 84.8) and a corresponding normal serum creatinine level. Creatinine clearance calculated by the Cockcroft-Gault formula did not correlate well with that measured by the 24-h endogenous clearance (r = 0.426) and 99mTc-DTPA clearance (r = 0. 366), overestimating creatinine clearance in all but three patients. The mean (SD) difference between the creatinine clearance measured by the 24-h and DTPA clearance technique was 17.7 (16.5)% and the correlation between these techniques was good (r = 0.71). CONCLUSION: Serum creatinine level is not sensitive in detecting early deterioration of renal function in patients with SCI. The Cockcroft-Gault formula generally significantly overestimates the true creatinine clearance and is not recommended. The 24-h endogenous creatinine clearance measured on appropriately collected urine samples is an acceptable accurate and practical method of determining glomerular filtration rate in patients with SCI.

Adult↗

PubMed2000

Using peer feedback to improve handwashing and glove usage among Thai health care workers.

BACKGROUND: Without protective practices such as Universal Precautions, health care workers are at substantial risk for bloodborne infection, especially in areas such as Thailand with high prevalence of HIV infection. The purpose of this study was to evaluate the effectiveness of a peer feedback program (PFP) on handwashing and glove wearing (HW/GW) among Thai health care workers. METHODS: Subjects (N = 91) were randomly assigned to receive PFP versus no treatment. By using a checklist, peer observers rated HW/GW compliance in their coworkers during patient care. For 1 month, the investigator posted a report of compliance behaviors from each 3 days of observations. HW/GW was also assessed by the investigator by direct observation at 1 month before the intervention, during the intervention period, and 1 month after the intervention. RESULTS: Baseline HW/GW rates for the PFP and control groups were 49.2% and 61.5%, respectively. The PFP group had a significantly higher adjusted compliance rate than the control group during the intervention period (P =.0001). However, there was no significant difference in the compliance scores obtained 1 month after the intervention. CONCLUSIONS: The PFP was effective during the intervention period, but there was no retention of effect. Therefore, adjunct methods should be sought to promote retention of effect.

Adult↗

PubMed2000

Bing de ling, a Chinese herbal formula, stimulates multifaceted immunologic responses in mice.

Bing de ling is a Chinese herbal formula most commonly used in complementary medical settings against viral disorders. We have found that bing de ling potentiates upregulation of immune activity when administered to mice in dosages proportional to those used clinically. These mice demonstrated significant elevation of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production in splenocytes and enhancement of macrophage, natural killer cell, and lymphokine-activated killer cell cytotoxicity. These data are consistent with bing de ling's clinically observed efficacy against viruses and identify the formula as a promising candidate for clinical trials against diverse diseases that may respond to increased immunologic activity.

Adjuvants, Immunologic↗

PubMed2000

Relationships between perception of engagement with health care provider and demographic characteristics, health status, and adherence to therapeutic regimen in persons with HIV/AIDS.

The purpose of this descriptive, correlational study was to examine the relationships between perception of engagement with health care provider and demographic characteristics, health status, and adherence to therapeutic regimen in persons with HIV/AIDS. The convenience sample of 707 non-hospitalized persons receiving health care for HIV/AIDS was recruited from seven U.S. sites. All measures were self-report. Perception of engagement with health care provider was measured by the newly developed Engagement with Health Care Provider scale. Adherence to therapeutic regimen included adherence to medications, provider advice, and appointments. Health status was measured by the Medical Outcomes Study Short Form 36 (MOS SF-36), Living with HIV scale, CD4 count, and length of time known to be HIV-positive. There were no significant relationships between engagement with health care provider and age, gender, ethnicity, and type of health care provider. Subscales of the MOS SF-36 and Living with HIV explained a significant, but modest amount of the variance in engagement. Clients who were more engaged with their health care provider reported greater adherence to medication regimen and provider advice. Clients who missed at least one appointment in the last month or who reported current or past injection drug use were significantly less engaged.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Use of (99m)Tc-DISIDA biliary scanning with morphine provocation for the detection of elevated sphincter of Oddi basal pressure.

BACKGROUND: Endoscopic biliary manometry is useful in the assessment of patients with types II and III sphincter of Oddi dysfunction, but it is time consuming and invasive. AIM: To investigate the role of (99m)Tc-DISIDA scanning, with and without morphine provocation, as a non-invasive investigation in these patients compared with endoscopic biliary manometry. SUBJECTS AND METHODS: A total of 34 patients with a clinical diagnosis of type II (n = 21) or III (n = 13) sphincter of Oddi dysfunction were studied. Biliary scintigraphy with 100 MBq of (99m)Tc-DISIDA was carried out with and without morphine provocation (0.04 mg/kg intravenously) and time/activity curves were compared with the results of subsequent endoscopic biliary manometry. RESULTS: Eighteen (nine type II, nine type III) of the 34 (53%) patients had sphincter of Oddi basal pressures above the upper limit of normal (40 mm Hg). In the standard DISIDA scan without morphine, no significant differences were observed in time to maximal activity (Tmax) or percentage excretion at 45 or 60 minutes between those with normal and those with abnormal biliary manometry. However, following morphine provocation, median percentage excretion at 60 minutes was 4.9% in those with abnormal manometry and 28.2% in the normal manometry group (p = 0.002). Using a cut off value of 15% excretion at 60 minutes, the sensitivity for detecting elevated sphincter of Oddi basal pressure by the morphine augmented DISIDA scan was 83% and specificity was 81%. Also, 14 of the 18 patients with abnormal manometry complained of biliary-type pain after morphine infusion compared with only two of 16 patients in the normal manometry group (p = 0.001). CONCLUSIONS: (99m)Tc-DISIDA with morphine provocation is a useful non-invasive investigation for types II and III sphincter of Oddi dysfunction to detect those with elevated sphincter basal pressures who may respond to endoscopic sphincterotomy.

Adult↗

PubMed2000

Alternative pathways of cell death to circumvent pleiotropic resistance in myeloma cells: role of cytotoxic T-lymphocytes.

Pleiotropic resistance to treatment remains one of the major reasons for therapeutic failures in patients with multiple myeloma. Myeloma cells are frequently resistant to physiological inducers of cell death prior to chemotherapy. Moreover, in the course of treatment cells acquire a multidrug resistant (MDR) phenotype, making eradication of the tumor even more difficult. A necessary prerequisite for circumventing complex pleiotropic resistance is therefore defining the signaling pathways that execute death in myeloma cells. This review discusses evidence that cytokine-expressing autologous tumor cell vaccine may be an efficient tool for elimination of both intrinsically resistant myeloma cells as well as cells with acquired MDR in murine models. The vaccine was similarly potent against wild type cells that were resistant to several death receptor ligands, and their isogenic sublines selected for P-glycoprotein-mediated MDR. The anti-myeloma effect of the vaccine was mediated by granzyme B/perforin-secreting cytotoxic T-lymphocytes. This is an example of therapeutic strategy directed at utilizing death pathways that are preserved in pleiotropically resistant tumor cells.

Cell Death↗

PubMed1999

Investigation of mutant frequency at the HPRT locus and changes in microsatellite sequences in healthy young adults.

In an attempt to understand the inter-individual variation that occurs in in vivo mutant frequency at the HPRT locus, we have examined the effect of polymorphisms in genes for metabolic enzymes on the mutation rate. In the same population of human volunteers, the background variant frequency in a number of microsatellite sequences was studied to determine individual variation in the capacity to repair mismatches in these sequences. The HPRT mutant frequency of T-cells isolated from a group of 49 healthy, non-smoking adults varied from 0.25 to 9.64 x 10(-6). The frequency of polymorphisms in CYP1A1, GSTM1 and NAT2 among these individuals was similar to those published, and when subjected to univariate analysis these polymorphisms showed no influence on the HPRT mutant frequency. However, there was a significant interaction between the GSTM1 null genotype and the slow acetylator status in NAT2 (P < 0.05) which was associated with higher mutant frequency. Analysis of 30 microsatellite sequences in 20 HPRT proficient clones per individual showed only six alterations in total, giving an overall mutation rate per allele of 0.01%, whilst three alterations were found in five HPRT deficient clones per individual examined for changes in 10 microsatellites, giving an overall mutation rate per allele of 0.3%. Thus, the alterations detected are probably due to background mutations and not to differences in mismatch repair capacity.

Adolescent↗

PubMed1999

Cytokine-based tumor cell vaccine is equally effective against parental and isogenic multidrug-resistant myeloma cells: the role of cytotoxic T lymphocytes.

Tumor cells that survive initial courses of chemotherapy may do so by acquiring a multidrug-resistant phenotype. This particular mechanism of drug resistance may also confer resistance to physiological effectors of apoptosis that could potentially reduce the efficacy of immune therapies that use these pathways of cell death. We have previously demonstrated high efficacy for a cytokine-based tumor cell vaccine in a murine MPC11 myeloma model. In the present study, the effects of this vaccination were compared in MPC11 cells and their isogenic sublines selected for mdr1/P-glycoprotein (Pgp)-mediated multidrug resistance (MDR). Immunization with MPC11 cells expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-12 (IL-12) led to long-lasting protection of mice against subcutaneous (sc) challenge with both parental cells or their MDR variants. Similarly, immunization with GM-CSF/IL-12-transfected MDR sublines caused rejection of transplantation of both parental cells and the MDR sublines. Whereas MPC11 cells and their MDR variants were resistant to APO-1/CD95/Fas ligand, the immunization generated potent granzyme B/perforin-secreting cytotoxic T lymphocytes (CTLs) that were similarly effective against both parental and isogenic MDR cells. We conclude that MDR mediated by mdr1/Pgp did not interfere with lysis by pore-forming CTLs. Immunotherapy based on pore-forming CTLs may be an attractive approach to the treatment of drug-resistant myeloma.

Animals↗

PubMed1999

Job analysis 1996: Infection control professional. Certification Board in Infection Control and Epidemiology, Inc, 1996 Job Analysis Committee.

The Certification Board in Infection Control and Epidemiology, Inc, directed its Test and Administrative Subcommittees to compose a Job Analysis Committee in 1995. This 16-member Job Analysis Committee, in collaboration with Applied Measurement Professionals, Inc, conducted a job analysis survey of infection control professionals in the United States and Canada during 1996. The reassessment of the previous Certification Board in Infection Control and Epidemiology, Inc, task analysis, formation of a job-analysis survey tool, the actual job-analysis process, and its results are described in this article. The previous and newly revised test specification outlines are compared. The Revised Certification Examination for Infection Control offered beginning in 1997 will reflect the efforts of this endeavor.

Canada↗