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Biomedical subjects

J C Young

Publications and source records attributed to J C Young.

At least 19 recordsLinked to original sources

Factors affecting measurement of specific methanogenic activity.

Specific methane production (SMP) tests have been used to determine the potential loading rate capacity of anaerobic reactors, to characterize biomass prior to its use as an inoculum for new anaerobic reactors, to detect changes in biomass activity during operation, or to assess the occurrence of toxic conditions. SMP tests also provide a basis for estimating specific methanogenic activity in mixed anaerobic cultures. SMP protocols used to date have varied widely in both procedure and objective. Tests conducted by the present authors indicated that biomass concentration, substrate type and concentration, and mixing intensity are factors that can affect the results of SMP tests.

Acetates↗

The impact of introducing laparoscopic donor nephrectomy to an established renal transplant program.

BACKGROUND: Although the advent of hand-assisted laparoscopic donor nephrectomy (HLDN) has had a positive impact on the donor pool, there is still some concern about its safety. The aim of this study was to assess the impact of a change in surgical access to live-donor nephrectomy on donor-related complication rates, the renal function of the donor, and the graft function of the recipient. METHODS: At our hospital, HLDN was introduced in 1998. Thereafter, we compared 49 consecutive donors undergoing open donor nephrectomy (ODN) between 1987 and 2002 with 57 consecutive donors undergoing HLDN between 1998 and 2002. Donor renal and recipient graft functions were assessed by measuring creatinine levels and urine output, with the addition of warm and cold ischemia time and dialysis requirements in the latter group. Data are presented as means (+/-SD) and analyzed with the Student t-test or Fisher's exact test. RESULTS: The ODN and HLDN donors were comparable for age, gender, body mass index, renovascular anatomy, and preoperative creatinine. Estimated blood loss (370 +/- 280 vs 168 +/- 160 ml, p < 0.0001), time to resumption of oral intake (1.7 +/- 0.5 vs 1.3 +/- 0.7 days, p = 0.01), duration of intravenous narcotic requirements (23 +/- 0.7 vs 1.7 +/- 1.0 days, p < 0.0001), and hospital stay (4.2 +/- 1.4 vs 2.9 +/- 1.3 days, p < 0.0001) were significantly decreased after HLDN. There were no significant differences between ODN and HLDN in operating time (204 +/- 46 vs 202 +/- 49 min), donor-related complication rates (12.2% vs 14%), or donor renal and recipient graft functions. CONCLUSION: The introduction of HLDN to an established renal transplant program led to an improved short-term outcome without any increase in donor-related complication rates or delay in recipient graft function.

Female↗

Inhibitors of histone deacetylases promote hematopoietic stem cell self-renewal.

BACKGROUND: Histone deacetylases (HDAC) are associated with a variety of transcriptional repressors that control cellular differentiation and proliferation. HDAC inhibitors such as trichostatin A, trapoxin and chlamydocin could be useful tools to modulate these cellular processes. We investigated their effect on the self-renewal of hematopoietic stem cells (HSC) during ex vivo culture. METHODS: Purified murine HSC with the phenotype c-Kit+,Thy-1.1(lo), Lin(-/lo), Sca-1+ were cultured for 4 days with IL-3, IL-6 and c-Kit ligand without or with HDAC inhibitors, after which their degree of phenotypic differentiation in culture was assessed by flow cytometric analysis. To explore whether HDAC inhibitors could have a beneficial role in human HSC transplantation, mobilized peripheral blood CD34+ cells were cultured with thrombopoietin mimetic peptide, flt3 ligand, and c-Kit ligand, without or with various HDAC inhibitors. The fluorescent dye, carboxyfluorescein-diacetate succinimidylester (CFSE), was used to track division of cell subsets, and engrafting ability was evaluated in a non-obese diabetic (NOD) -SCID xenotransplantation model. RESULTS: Murine HSC cultured with HDAC inhibitors maintained a more primitive phenotype than control cultures. The number of human HSC expressing Thy-1 increased up to seven-fold during a 5-day culture with HDAC inhibitors compared with control cultures. Chlamydocin was the most effective of the HDAC inhibitors tested at promoting Thy-1 expression on human cells. CFSE tracking showed that the increase in Thy-1+ cells resulted from cell division. In a NOD-SCID repopulation assay, cells exposed to chlamydocin for 24 h displayed an average four-fold higher engrafting ability over control cells. DISCUSSION: Our studies suggest that HDAC inhibitors can induce ex vivo expansion of human HSC, and may improve engraftment in hematopoietic transplant patients when cell dose is limiting.

Animals↗

Effect of organics on sulfur-utilizing autotrophic denitrification under mixotrophic conditions.

Sulfur-utilizing denitrification can be performed by denitrifying sulfur bacteria under autotrophic and heterotrophic conditions. To investigate the effect of organics (methanol and landfill leachate) on sulfur-utilizing denitrification, six laboratory-scale sulfur packed columns were operated under autotrophic, mixotrophic and heterotrophic conditions for approximately 1 year. The performance of the columns was monitored by measuring the pH, nitrate, nitrite, sulfate, sulfide, alkalinity dissolved organic carbon (DOC), and turbidity. These tests indicated that the mixotrophic column had a higher nitrate removal capacity than the autotrophic column. It was also found that under mixotrophic conditions, some portion of nitrate was removed heterotrophically and the remainder was denitrified by sulfur-utilizing autotrophic bacteria without inhibition by organics. In addition, sulfate production and alkalinity consumption were reduced under mixotrophic conditions. These results suggest that mixotrophic conditions that allow simultaneous reactions of autotrophic and heterotrophic denitrification provide significant advantages in terms of nitrate and DOC removal, sulfate production decrease, and alkalinity consumption over obligate autotrophic or heterotrophic denitrification.

Bacteria↗

Modulation of cell proliferation by heterotrimeric G protein in Arabidopsis.

The alpha subunit of a prototypical heterotrimeric GTP-binding protein (G protein), which is encoded by a single gene (GPA1) in Arabidopsis, is a modulator of plant cell proliferation. gpa1 null mutants have reduced cell division in aerial tissues throughout development. Inducible overexpression of GPA1 in Arabidopsis confers inducible ectopic cell division. GPA1 overexpression in synchronized BY-2 cells causes premature advance of the nuclear cycle and the premature appearance of a division wall. Results from loss of function and ectopic expression and activation of GPA1 indicate that this subunit is a positive modulator of cell division in plants.

2,4-Dichlorophenoxyacetic Acid↗

ABP1 is required for organized cell elongation and division in Arabidopsis embryogenesis.

To directly address the function of a putative auxin receptor designated ABP1, a reverse genetic approach was taken to identify and characterize ABP1 mutant alleles in Arabidopsis. A homozygous null mutation in ABP1 confers embryo lethality. Null mutant embryos develop normally until the early stages of the globular embryo but are unable to make the transition to a bilaterally symmetrical structure because cells fail to elongate. Cell division was also aberrant both in the suspensor and embryo proper. Antisense suppression of ABP1 in tobacco cells causes slow proliferation and eliminates auxin-induced cell elongation and reduces cell division. The complete lack of auxin-inducible elongation in individual cells confirms the results observed in embryos, indicates a cell autonomous function, and, taken together with biochemical evidence that ABP1 binds auxins, suggests that ABP1 mediates auxin-induced cell elongation and, directly or indirectly, cell division.

Alleles↗

Do protective factors reduce the risk of hospitalization in infants of teenaged mothers?

OBJECTIVE: To determine the risk of hospitalization associated with prenatal care use and indicators of socioeconomic status and social support among infants of teenage mothers. DESIGN: Population-based case-control study. SETTING: Nonfederal hospitals in Washington State. PARTICIPANTS: Infants born from 1987 to 1995 to mothers younger than 20 years were identified using linked birth certificate-state hospital discharge data. Cases consisted of 8052 infants who were hospitalized during the first year of life at least 2 days after birth hospitalization discharge. An equal number of controls, frequency matched on birth year and maternal age group, were randomly sampled from among nonhospitalized infants. MAIN OUTCOME MEASURE: Hospitalization in the first year of life. RESULTS: Infants with a father listed on the birth certificate or whose mothers had commercial health insurance had a decreased risk of hospitalization (adjusted odds ratios, 0.91 and 0.78, respectively; 95% confidence intervals, 0.83-0.99 and 0.71-0.85, respectively). Participation in state-funded pregnancy programs, adequacy of prenatal care, or marital status did not affect the risk of hospitalization, except among infants whose mothers received more than adequate prenatal care (adjusted odds ratio, 1.15; 95% confidence interval, 1.03-1.29). CONCLUSION: Our results suggest that teenaged mothers who list a father on the birth certificate or who have insurance, indicative of higher socioeconomic status, may have a reduced risk of hospitalization for their infants. Teenaged mothers who receive more than adequate prenatal care may have pregnancy complications that place their infants at increased risk of hospitalization. The effect of these protective factors should be clarified in future studies.

Adolescent↗

Can paramedics using guidelines accurately triage patients?

STUDY OBJECTIVE: We determine whether paramedics, using written guidelines, can accurately triage patients in the field. METHODS: This prospective, descriptive study was conducted at an urban county emergency medical services (EMS) system and county hospital. Paramedics triaged patients, for study purposes only, according to 4 categories: (1) needing to come to the emergency department by advanced life support (ALS) transport, (2) needing to come to the ED by any transport, (3) needing to see a physician within 24 hours, or (4) not needing any further physician evaluation. Medical records that provided patient treatment information to the point of ED disposition were subsequently reviewed (blinded to the paramedic rating) to determine which of the categories was appropriate. The protocol of the EMS system of the study site dictates that all patients should be transported except for those who refuse care and leave against medical advice. Only transported patients were included in the present study. Fifty-four paramedics triaged 1,180 patients. RESULTS: Mean patient age was 43.4+/-17 years; 62.0% were male. Paramedics rated 1,000 (84.7%) of the patients as needing to come to the ED and 180 (15.3%) as not needing to come to the ED. Ratings according to triage category were as follows: 804 (68.1%) category 1, 196 (16.6%) category 2, 148 (12.5%) category 3, and 32 (2.7%) category 4. Seven hundred thirty-six (62.4%) patients were discharged, 298 (25.3%) were admitted, 90 (7.6%) were transferred, 36 (3.1%) left against medical advice, and 20 (1.7%) died. The review panel determined that 113 (9.6%) patients were undertriaged; 55 (48.7%) of these patients were misclassified because the paramedics misused the guidelines. Ninety-nine patients (8.4% of the total sample) were incorrectly classified as not needing to come to the ED. This represented 55% of the patients (99/180) categorized as 3 or 4 by the paramedics. Fourteen patients (1.2% of total) were incorrectly classified as category 4 instead of 3. Of the 113 undertriaged patients, 22 (19.6%) were admitted, 86 (76.1%) were discharged, and 4 (3.5%) were transferred. CONCLUSION: Paramedics using written guidelines fall short of an acceptable level of triage accuracy to determine disposition of patients in the field.

Adolescent↗

Investigation into an engraftment defect induced by culturing primitive hematopoietic cells with cytokines.

BACKGROUND: Strategies for transplanting primitive hematopoietic progenitor (PHP) cells are under development that require in vitro manipulation of cells for several hours to several days prior to transplantation. This applies to gene-therapy protocols involving transduction with adenoviral or lentiviral vectors (typically 1 day of ex vivo culture) or retroviral vectors (up to 3 days of culture). METHODS: Human mobilized peripheral blood (MPB) CD34(+) cells were cultured with the cytokines thrombopoietin mimetic peptide (mTPO), flt3 ligand (FL), and c-kit ligand (KL). Equal numbers of CD34(+) cells, either uncultured or cultured for various time periods up to 5 days, were tested for engraftment in sublethally irradiated 8-10 week-old NOD/SCID mice. Cells were also compared for expression and function of several key surface molecules. RESULTS: At a limiting dose of 1 million cells, mice receiving uncultured cells had a mean of 20% CD45(+) (human) cells in their BM 6 weeks post-transplantation, versus 3% for mice receiving 3-5 day cultured cells. Analysis of 10 surface molecules, CD11a, CD18, CD29, CD49d, CD49e, CXCR-4, CD62L, CD31, CD43, and CD44 over a 5-day culture period showed that their expression levels were either maintained or up-regulated on CD34(+) cells and the primitive Thy-1(+) subset. Similar percentages of uncultured and 3-day cultured MPB CD34(+) cells bound to plates coated with vascular cell adhesion molecule-1 (VCAM-1) under both static and physiological flow conditions, and chemotaxis of cultured cells towards stromal-derived factor-1 (SDF-1) was not impaired, suggesting that VLA-4 and CXCR-4 were functional on cultured cells. CD34(+) Thy-1(+) MPB cells cultured with cytokines expressed increasing levels of Fas receptor beginning at 20 h in culture, with peak expression levels after 3 days (mean Day 0 expression, 39%; mean Day 3 expression, 86%), without increased apoptosis. Including inhibitors of caspases in the media of cells cultured for 24-48 h significantly improved their engraftment in a SCID-hu bone-engraftment model. DISCUSSION: Increased susceptibility to apoptosis upon in vivo injection may contribute to impaired engraftment of in vitro manipulated cells. Inhibitors of apoptosis may increase their engrafting capacity in clinical settings.

Animals↗

Hantavirus pulmonary syndrome: at the crossroads.

The initial identification in 1993 of hantavirus pulmonary syndrome as a novel, highly fatal respiratory illness among American Indians in the southwestern USA in 1993 opened the window to the recognition of a well-established pan-American zoonosis with a myriad of causative viruses and rodent vectors, although all are New World hantaviruses among New World sigmodontine rodents. The clinical spectrum of symptoms has also been expanded to include asymptomatic infection through to fulminant hemorrhagic fever. Although the use of ribavirin, an antiviral drug, was disappointing in an early, open-labeled trial, early detection and supportive care is much better refined. However, much work remains in probing the pathogenesis of this syndrome to help define and explore therapeutic options and the mechanism of person-to-person transmission with Andes virus, one of the viruses that cause hantavirus pulmonary syndrome. Current remote sensing efforts and longitudinal ecologic investigations need to be expanded in order to focus prevention efforts better.

Animals↗

Efficient screening of Arabidopsis T-DNA insertion lines using degenerate primers.

The sequencing of the Arabidopsis plant genome is providing a fuller understanding of the number and types of plant genes. However, in most cases we do not know which genes are responsible for specific metabolic and signal transduction pathways. Analysis of gene function is also often confounded by the presence of multiple isoforms of the gene of interest. Recent advances in PCR-based reverse genetic techniques have allowed the search for plants carrying T-DNA insertions in any gene of interest. Here we report preliminary screening results from an ordered population of nearly 60,470 independently derived T-DNA lines. Degenerate PCR primers were used on large DNA pools (n = 2,025 T-DNA lines) to screen for more than one gene family member at a time. Methods are presented that facilitated the identification and isolation of isoform-specific mutants in almost all members of the Arabidopsis H(+)-proton ATPase gene family. Multiple mutant alleles were found for several isoforms.

Arabidopsis↗

Patient and provider attitudes toward commercial television film crews in the emergency department.

UNLABELLED: One of the most successful reality-based television shows is The Learning Channel's "Trauma-Life in the ER," in which patients are filmed prior to being consented and camera crews are intimately intertwined in resuscitations. OBJECTIVE: To assess provider and patient attitudes regarding privacy and satisfaction during filming. METHODS: This was a prospective survey of patients and providers working in an urban, county teaching emergency department (ED). Scores of visual analog scales (VASs) for satisfaction, privacy, and willingness to return to the ED were accessed. RESULTS: Eighty patients, 39 physicians and 39 nurses, were interviewed. On a 10-cm VAS where 0 = no invasion of patient privacy and 10 = extreme privacy invasion, the mean (+/-SD) rating by physicians was 5.4 (+/-2.6), by nurses was 4.9 (+/-3.1), and by patients was 2.3 (+/-3.2). There was no significant difference between physician and nurse ratings (p = 0.69), but patients rated invasion of privacy significantly lower (p < 0.0001). Filmed patients rated significantly higher invasion of privacy (3.8 +/- 4.1) than patients not filmed or those unsure whether they had been filmed (1.6 +/- 2.5); p < 0.01). On a 10-cm VAS where -5 = extreme decrease in satisfaction and 5 = extreme increase in satisfaction, the mean rating by physicians was -0.25 (+/-1.6), by nurses was -0.32 (+/-1.3), and by patients was 0.02 (+/-1.4). There was no statistical difference between the satisfaction levels of providers and patients (p = 0.19). CONCLUSIONS: Providers rated invasion of patient privacy higher than patients rated their own invasion of privacy. Patients who were filmed rated invasion of privacy higher than patients who were not filmed. Filming had no significant effect on the satisfaction of providers or patients.

Adolescent↗

Synergistic inhibition of the glucocorticoid receptor by radicicol and benzoquinone ansamycins.

Radicicol (RAD) and the benzoquinone ansamycin geldanamycin (GA) are potential anticancer drugs known to inhibit heat shock protein 90 (hsp90) and, therefore, the activation of proteins dependent on its function such as proto-oncogenic kinases and nuclear receptors. Using the glucocorticoid receptor (GR) as a model system we analysed the effects of RAD and various benzoquinone ansamycins. All compounds efficiently abolished GR-dependent transactivation. Surprisingly, whenever one of the ansamycins was applied in combination with RAD, synergistic inhibition of GR-dependent transcription and of hormone binding of GR was observed. In contrast, combination of two ansamycins showed no synergy. These findings suggest synergism within the hsp90 dimer and may open new ways to explore hsp90 as therapeutic target.

Anti-Bacterial Agents↗

Organized sports for children and preadolescents.

Participation in organized sports provides an opportunity for young people to increase their physical activity and develop physical and social skills. However, when the demands and expectations of organized sports exceed the maturation and readiness of the participant, the positive aspects of participation can be negated. The nature of parental or adult involvement can also influence the degree to which participation in organized sports is a positive experience for preadolescents. This updates a previous policy statement on athletics for preadolescents and incorporates guidelines for sports participation for preschool children. Recommendations are offered on how pediatricians can help determine a child's readiness to participate, how risks can be minimized, and how child-oriented goals can be maximized.

Age Factors↗

Strength training by children and adolescents.

Pediatricians are often asked to give advice on the safety and efficacy of strength training programs for children and adolescents. This review, a revision of a previous American Academy of Pediatrics policy statement, defines relevant terminology and provides current information on risks and benefits of strength training for children and adolescents.

Adolescent↗