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Biomedical subjects

K Roberts

Publications and source records attributed to K Roberts.

At least 37 records · Page 2Linked to original sources
PubMed2001

Differential expression of cell-wall-related genes during the formation of tracheary elements in the Zinnia mesophyll cell system.

Plants, animals and some fungi undergo processes of cell specialization such that specific groups of cells are adapted to carry out particular functions. One of the more remarkable examples of cellular development in higher plants is the formation of water-conducting cells that are capable of supporting a column of water from the roots to tens of metres in the air for some trees. The Zinnia mesophyll cell system is a remarkable tool with which to study this entire developmental pathway in vitro. We have recently applied an RNA fingerprinting technology, to allow the detection of DNA fragments derived from RNA using cDNA synthesis and subsequent PCR-amplified fragment length polymorphisms (cDNA-AFLP), to systematically characterize hundreds of the genes involved in the process of tracheary element formation. Building hoops of secondary wall material is the key structural event in forming functional tracheary elements and we have identified over 50 partial sequences related to cell walls out of 600 differentially expressed cDNA fragments. The Zinnia system is an engine of gene discovery which is allowing us to identify and characterize candidate genes involved in cell wall biosynthesis and assembly.

Cell Differentiation↗
PubMed2001

Claiming in the name of fairness: organizational justice and the decision to file for workplace injury compensation.

This article explored the relationship among injured workers' perceptions of workplace justice (i.e., distributive, interactional, and procedural), perceptions of employers' disability-related policies, and the decision to file a workers' compensation claim. Using a 2-wave sample of 1,077 workers with repetitive motion injuries, the authors tested a structural equation model. Results revealed that Time 1 interactional justice was negatively related to filing a claim, whereas Time 1 distributive justice was positively related to perceptions of employer disability-related practices measured a year after the date of injury report. At Time 2, the claim decision was unrelated to perceptions of justice, yet perceptions of disability-related practices were significantly related to all 3 types of justice.

Adult↗
PubMed2000

Differential cytotoxicity and induction of apoptosis in tumor and normal cells by hydroxymethylacylfulvene (HMAF).

This investigation compared the effects of hydroxymethylacylfulvene (HMAF), a novel antitumor drug with alkylating properties, in eight human tumor (prostate, colon, and leukemia) cell lines, and five human normal (prostate and renal proximal tubule epithelial, colon mucosa, fibroblasts, and endothelial) cell lines. Drug-induced growth inhibition paralleled the uptake of HMAF into both tumor and normal cells, although normal cells were 3- to 4-fold more tolerant to the accumulated drug. In both tumor and normal cells, approximately two-thirds of internalized [(14)C]HMAF-derived radioactivity was bound covalently to macromolecules. Trypan blue exclusion and cell counts indicated that HMAF was cytotoxic in tumor but cytostatic in normal cells. Correspondingly, profound apoptosis was detected in all tumor cell lines examined. A 4-hr treatment with HMAF followed by 20-hr post-incubation induced a potent DNA fragmentation in nearly all tumor lines. Apoptosis-resistant PC-3 and HT-29 cells underwent significant DNA fragmentation after 24 hr of continuous treatment with HMAF. In contrast to tumor cell lines, marginal or very low levels of apoptosis were detected in the normal cells even after prolonged treatments with HMAF at concentrations that exceeded 15- to 800-fold the GI(50) values in tumor cells. This resistance of normal cells to apoptosis could not be accounted for by differences in drug accumulation or drug covalent binding to macromolecules. The qualitatively different responses of the tumor and normal cells studied suggest a greater tolerance of normal cells to HMAF-macromolecular adducts. The demonstrated differential cytotoxic/cytostatic and apoptotic effects of HMAF can be of significance for the clinical use of this promising new agent.

Antineoplastic Agents↗
PubMed2000

Estimation of incidence of respiratory syncytial virus infection in schoolchildren using salivary antibodies.

An assay for respiratory syncytial virus (RSV)-specific IgG in saliva is described. The assay was used to examine the incidence of RSV infection in schoolchildren 7-10 years old during one RSV season. One hundred and twenty-one volunteer children provided saliva samples in October 1997 and March 1998; 18% of the children showed a fourfold or greater rise in anti-RSV IgG in the second sample. This prevalence of antibody increase is similar to that described in previous studies that measured CFT levels in serum samples. Overall, the children who showed rises in antibody levels, indicating that they had experienced an RSV infection, had lower levels of RSV-specific antibody in their preseason samples than those who showed no increase (P = 0.0018). These results show that saliva is an adequate substitute for serum in some antibody tests and may be useful for community studies. Such studies may provide surrogate markers for susceptibility to infection, which should benefit the planning of vaccination strategies.

Antibodies, Viral↗
PubMed2000

Clonal analysis of the Arabidopsis root confirms that position, not lineage, determines cell fate.

The cellular organization of the Arabidopsis thaliana (L.) Heynh. root meristem suggests that a regular pattern of cell divisions occurs in the root tip. Deviations from this pattern of division might be expected to disrupt the organization of cells and tissues in the root. A clonal analysis of the 3-d-old primary root meristem was carried out to determine if there is variability in division patterns, and if so to discover their effect on cellular organization in the root. Clones induced in the seedling meristem largely confirmed the predicted pattern of cell divisions. However, the cellular initials that normally give rise to the different cell files in the root were shown to exhibit some instability. For example, it was calculated that a lateral root cap/epidermal initial is displaced every 13 d. Furthermore, the existence of large marked clones that included more than two adjacent cell layers suggests that intrusive growth followed by cell division may occur at low frequency, perhaps in response to local cell deaths in the meristem. These findings support the view that even in plant organs with stereotypical cell division patterns, positional information is still the key determinant of cell fate.

Arabidopsis↗
PubMed2000

Xylogenesis: the birth of a corpse.

Xylogenesis is a complex developmental process culminating in programmed cell death as a truly terminal differentiation event. In Arabidopsis, the availability of vascular-patterning mutants, and the identification of genes and their products that are involved in cell specification, secondary-wall deposition and lignification, are providing clues to the functions of some of the sequences in the large expressed sequence tag databases derived from the xylem-rich tissues of trees. An in vitro system, the Zinnia mesophyll cell system, provides an alternative system for those cell-biological experiments that are difficult to tackle in intact plants. In particular, a combination of molecular-genetic and cell-biological approaches has made possible the elucidation of some of the features of plant programmed cell death.

Arabidopsis↗
PubMed2000

Monosomy 20 as a pointer to dicentric (9;20) in acute lymphoblastic leukemia.

Twenty new cases of acute lymphoblastic leukemia (ALL) with the dicentric chromosome dic(9;20)(p1113;q11) are presented. This chromosomal abnormality is difficult to identify from G-banding alone. It masquerades as monosomy 20 and is only accurately identified by fluorescence in situ hybridization (FISH). Monosomy 20 was found in 59/2790 patients with successful karyotypes entered to the Leukaemia Research Fund/UK Cancer Cytogenetics Group Karyotype Database in ALL (LRF/UKCCG Karyotype Database). FISH revealed dic(9;20) in 20/25 cases with available material. Extra copies of chromosome 21 were found in 8 of the 20 cases. Patients were 14 females and six males, aged 1-32 years (median 4 years), with leukocyte counts of 2-536 (median 23) x 109/l and immunophenotypes of common or pre-B ALL (17 cases), T-ALL (one case) or unknown (two cases). Four patients relapsed at 2, 22, 28 and 47 months and two died at 49 and 63 months (median follow-up 37 months). FISH studies on the remaining five patients showed one with monosomy 20 and four with other rearrangements of the chromosome. This study has increased the number of reported cases of dic(9;20) from 17 to 37. It has identified dic(9;20) in one case of T-ALL and shows an association of this translocation with trisomy 21.

Adolescent↗
PubMed2000

Why most workers with occupational repetitive trauma do not file for workers' compensation.

Despite the availability of no fault insurance for wage replacement and medical care costs, the majority of workers diagnosed with an occupational disease do not apply for workers' compensation. The objective of the study was to determine the reasons why workers diagnosed with work-related musculoskeletal disease did not apply for workers' compensation benefits. A cross-sectional study of 1598 individuals diagnosed with neck, upper extremity, and low back work-related musculoskeletal disease from April to June 1996 was performed. All individuals were interviewed over the telephone using a standardized questionnaire. The questionnaire included questions about the precipitating event; demographics; health limitations; mood; pain level; and attitudes toward their health care provider, fellow workers, management, work environment, and filing for workers' compensation. Whenever possible, standardized questions from previous surveys were used. The interviewed individuals with work-related musculoskeletal disease were reported by health care practitioners as required by the state of Michigan's occupational disease reporting law. Workers reported during 12 weeks in the spring of 1996 by a Michigan health care professional as having a neck, back, or upper extremity musculoskeletal disorder were eligible to participate. Among the 2703 reports received, 490 individuals could not be reached, 22 did not speak English, 12 had died or were too incapacitated by other medical conditions, and 581 refused. We interviewed 59% of all eligible workers and 73% of all workers who were reachable and capable of responding in English. Only 25% of workers diagnosed with musculoskeletal disease filed a workers' compensation claim. The factors significantly associated with filing a claim were (1) increased length of employment (> 21 years: odds ratio [OR], 3.01, 95% confidence interval [CI], 1.31 to 6.90); 11 to 20 years: OR, 2.34, 95% CI, 1.01 to 5.47; 6 to 10 years: OR, 1.76, 95% CI, 0.73 to 4.25; 1 to 5 years: OR, 2.36, 95% CI, 1.03 to 5.42; < 1 year: OR, 1.00; (2) lower annual income (< $40,000: OR, 1.75, 95% CI, 1.06 to 2.88 vs > or = $80,000: OR, 1.00); (3) workers' dissatisfaction with coworkers (OR, 1.76, 95% CI, 1.01 to 3.06); (4) physician restrictions on activity (OR, 2.16, 95% CI, 1.55 to 3.00); (5) type of physician providing treatment (specialist, including surgeon or orthopedist: OR, 3.63, 95% CI, 2.37 to 5.55); physical and occupational therapist: OR, 2.15, 95% CI, 1.35 to 3.43); family practitioner: OR, 1.33, 95% CI = 0.89 to 2.01; company physician: OR = 1.00); (6) off work > or = 7 days (OR, 14.85, 95% CI, 10.57 to 20.85); (7) decreased current health status (OR, 0.82, 95% CI, 0.70 to 0.96); and (8) increased severity of illness (OR, 1.24, 95% CI, 1.06 to 20.88). This study showed that only 25% of workers with a work-related musculoskeletal condition filed for workers' compensation and refutes the common perception that an individual with a work-related problem is likely to file a workers' compensation claim. The strongest predictors of who would file were those factors associated with the severity of the condition. Other factors were increasing length of employment, lower annual income, and worker dissatisfaction with coworkers. Our study population consisted mainly of unionized autoworkers, and our findings may not be generalizable to the total workforce.

Adolescent↗
PubMed2000

Genetic interactions during root hair morphogenesis in Arabidopsis.

Root hairs are a major site for the uptake of water and nutrients into plants and form an increasingly important model system for studies of development of higher plants and cell biology. We have identified loss-of-function mutations in eight new genes required for hair growth in Arabidopsis: SHAVEN1 (SHV1), SHV2, and SHV3; CENTIPEDE1 (CEN1), CEN2, and CEN3; BRISTLED1 (BST1); and SUPERCENTIPEDE1 (SCN1). We combined mutations in 79 pairs of genes to determine the stages at which these and six previously known genes contribute to root hair formation. Double mutant phenotypes revealed roles for several genes that could not have been predicted from the single mutant phenotypes. For example, we show that TIP1 and RHD3 are required much earlier in hair formation than previous studies have suggested. We present a genetic model for root hair morphogenesis that defines the roles of each gene, and we suggest hypotheses about functional relationships between genes.

Arabidopsis↗
PubMed2000

Virus-induced silencing of a plant cellulose synthase gene.

Specific cDNA fragments corresponding to putative cellulose synthase genes (CesA) were inserted into potato virus X vectors for functional analysis in Nicotiana benthamiana by using virus-induced gene silencing. Plants infected with one group of cDNAs had much shorter internode lengths, small leaves, and a "dwarf" phenotype. Consistent with a loss of cell wall cellulose, abnormally large and in many cases spherical cells ballooned from the undersurfaces of leaves, particularly in regions adjacent to vascular tissues. Linkage analyses of wall polysaccharides prepared from infected leaves revealed a 25% decrease in cellulose content. Transcript levels for at least one member of the CesA cellulose synthase gene family were lower in infected plants. The decrease in cellulose content in cell walls was offset by an increase in homogalacturonan, in which the degree of esterification of carboxyl groups decreased from approximately 50 to approximately 33%. The results suggest that feedback loops interconnect the cellular machinery controlling cellulose and pectin biosynthesis. On the basis of the phenotypic features of the infected plants, changes in wall composition, and the reduced abundance of CesA mRNA, we concluded that the cDNA fragments silenced one or more cellulose synthase genes.

Base Sequence↗
PubMed2000

Syndrome X: medical nutrition therapy.

A significant number of Americans are at risk for developing a condition of insulin resistance termed Syndrome X. Dyslipidemia, resistance to insulin, obesity, and blood pressure elevation--the deadly quartet--describe Syndrome X, which increases atherogenic risk and contributes to coronary artery disease. Lifestyle factors such as overeating and physical inactivity play a pivotal role in Syndrome X. This deadly duet has been aptly coined "hyperactive fork" and "hypoactive foot," respectively. In addition, emerging evidence suggests that certain nutrients may help protect against Syndrome X. This review provides a brief discussion of diet and lifestyle factors related to Syndrome X.

Arteriosclerosis↗
PubMed2000

Targeting apoptosis by hydroxymethylacylfulvene in combination with gamma radiation in prostate tumor cells.

Hydroxymethylacylfulvene (HMAF) is a novel agent with alkylating activity and is a potent inducer of apoptosis that is currently undergoing Phase II clinical trials for prostate cancer. This study explored the pro-apoptosis and anti-proliferative potential of HMAF in combination with gamma radiation in human prostate tumor cell lines. Apoptosis was assessed based on the generation of fragmented DNA, a terminal transferase flow cytometry assay, and cell morphology. In each of the tumor cell lines examined, radiation alone induced a marginal level of apoptosis, even after a prolonged 48-h incubation after exposure. In contrast, HMAF alone was a potent inducer of apoptosis in prostate tumor cells but not in normal cells. Marked levels of apoptosis in tumor cells were also observed for the combination of HMAF with gamma radiation. When drug treatment preceded irradiation, at least additive levels of apoptosis were observed in both androgen-responsive and androgen-independent cells. The combined treatment with ionizing radiation and HMAF reduced the radiation dose needed for the same level of clonogenic survival up to 2.5-fold. The potentiation of apoptosis and reduction in the clonogenic survival of tumor cells occurred at HMAF concentrations lower than that which reduced survival to 10% and at doses up to 6 Gy. No potentiation of apoptosis or clonogenic inhibition was noted in normal cells. These results suggest that the combination of HMAF with gamma radiation may have clinical utility for treatments of prostate cancer.

Adenocarcinoma↗
PubMed2000

Knowledge, attitudes, and practices of parents of asthmatic children in Cape Town.

To obtain information useful to asthma care in a relatively poor, high asthma prevalence population, a focus group study was undertaken with 72 parents of children with asthma or recurrent wheezing. There was a reasonable level of understanding of the causes of asthma, although variable acceptance of the diagnosis. Willingness to undertake home management of acute episodes and environmental control measures was high. Reported treatment was characterized by reliance on syrups, use of home remedies, resistance to inhaled therapy, and relatively low compliance with prescribed treatment. There was agreement on the poor level of service offered by doctors and public sector clinics. Asthma education in this population needs to build on what parents know and accept, but stress the relative safety of inhaled therapy, the need for maintenance therapy, and the value of pre-exercise prophylaxis, house dust mite control, and smoking cessation. There is an urgent need to improve the quality of asthma care provided by public sector clinics.

Adult↗
PubMed1999

Essential role for both CD80 and CD86 costimulation, but not CD40 interactions, in allergen-induced Th2 cytokine production from asthmatic bronchial tissue: role for alphabeta, but not gammadelta, T cells.

CD80 and CD86 interact with CD28 and deliver costimulatory signals required for T cell activation. We demonstrate that ex vivo allergen stimulation of bronchial biopsy tissue from mild atopic asthmatic, but not atopic nonasthmatic, subjects induced production of IL-5, IL-4, and IL-13. Explants from both study groups did not produce IFN-gamma, but secreted the chemokine RANTES without any overt stimulation. In addition to allergen, stimulation of asthmatic explants with mAbs to CD3 and TCR-alphabeta but not TCR-gammadelta induced IL-5 secretion. Allergen-induced IL-5 and IL-13 production by the asthmatic tissue was inhibited by anti-CD80 and, to a lesser extent, by anti-CD86 mAbs. In contrast, the production of these cytokines by PBMCs was not affected by mAbs to CD80, was inhibited by anti-CD86, and was strongly attenuated in the presence of both Abs. FACS analysis revealed that stimulated asthmatic bronchial tissue was comprised of CD4+ T cells that expressed surface CD28 (75. 3%) but little CTLA-4 (4.0%). Neutralizing mAbs to CD40 ligand had no effect on the cytokine levels produced by asthmatic tissue or PBMCs. Collectively, these findings suggest that allergen-specific alphabeta T cells are resident in asthmatic bronchial tissue and demonstrate that costimulation by both CD80 and CD86 is essential for allergen-induced cytokine production. In contrast, CD86 appears to be the principal costimulatory molecule required in PBMC responses. Attenuation of type 2 alphabeta T cell responses in the bronchial mucosa by blocking these costimulatory molecules may be of therapeutic potential in asthma.

Adult↗
PubMed1999

Gemcitabine--a novel immunosuppressive agent--prevents rejection in a rat cardiac transplantation model.

BACKGROUND: 2',2' -difluorodeoxycytidine (dFdC, gemcitabine) is a pyrimidine antimetabolite with antineoplastic activity against a wide range of solid tumors. The immunosuppressive activities of this compound have not been described to date. METHODS: The in vitro effects on activated T lymphocytes were studied with a lymphocyte colony-forming assay in a microagar culture system. Heart transplantations were performed in the fully allogeneic Lewis/ Brown Norway combination. dFdC was administered once daily at various dosages from the time of surgery until day 50. RESULTS: Phytohemagglutinin-induced lymphocyte proliferation was inhibited 50% by dFdC at a concentration of 3.25+/-0.9 nmol/L. Allografts of untreated animals survived for 7.5 (7-8) days and those with 25, 50, and 75 microg/kg body weight dFdC for 7.3 (7-8), 9.3 (8-10), and 16.3 (10-38) days, respectively. Treatment with 100 or 125 microg/kg body weight of dFdC, however, prolonged allograft survival until day 152.8 (129-178). Dose-dependent leukopenia was the main toxicity. CONCLUSIONS: DFdC is a new immunosuppressive agent that can successfully prevent cardiac rejection in a rat transplantation model.

Animals↗
PubMed1999

Bioassay-directed fractionation of PAH of molecular mass 302 in coal tar-contaminated sediment.

Bioassay-directed fractionation was used to characterise genotoxic polycyclic aromatic hydrocarbons (PAH) of molecular mass 302 amu in organic solvent extracts of coal tar-contaminated sediment from Sydney Harbour, Nova Scotia. A normal phase HPLC technique was employed to separate PAH-rich solvent extracts into fractions containing PAH of single molecular mass classes. The 302 amu molecular mass fraction was isolated and further separated using reversed phase HPLC; subfractions were collected every 30 s and subjected to bioassay analyses with Salmonella typhimurium strain YG1025 with the addition of oxidative metabolism (4% S9). Compounds eluting in the most active subfractions included naphtho[2,1-alpha]pyrene and naphtho[2,3-alpha]pyrene. The results of this study underscore the significant contribution that molecular mass 302 PAH make to the biological activity of complex environmental mixtures.

Biological Assay↗