Search PubMed⌕ Search

Biomedical subjects

D Jones

Publications and source records attributed to D Jones.

At least 127 records · Page 7Linked to original sources
PubMed2000

The NED-8 conjugating system in Caenorhabditis elegans is required for embryogenesis and terminal differentiation of the hypodermis.

This work has identified the enzymes involved in the activation and conjugation of the ubiquitin-like protein NED-8 in Caenorhabditis elegans. A C. elegans conjugating enzyme, UBC-12, is highly specific in its ability to utilize NED-8 as a substrate. Immunostaining shows that NED-8 is conjugated in vivo to a major target protein with a conjugate size of 90 kDa. While the amount of this conjugate is developmentally regulated with reduced levels in the larval stages, the mRNA encoding C. elegans UBC-12 is constitutively produced throughout development, as is NED-8 itself. The importance of the NED-8 conjugating system in C. elegans was determined by RNA interference (RNAi) assays using double-stranded RNA encoding NED-8, UBC-12, or the NED-8 activating enzyme component ULA-1. The progeny of both ned-8 and ubc-12 RNAi-treated hermaphrodites either arrested during embryonic development or underwent abnormal postembryonic development. The effect on postembryonic development was pleiotropic, the most frequent gross abnormality being vulval eversion during the L4 stage. Individuals with an everted vulva either burst at the L4 to adult molt or gave rise to adults incapable of egg laying. Additionally, both ned-8 and ubc-12 RNAi induced a striking abnormality in the alae, structures produced by the lateral hypodermal seam cells in the adult nematode. Affected alae were patchy and frequently diverged around a central space. Vulval defects were also produced by RNAi directed at C. elegans ula-1. This is the first demonstration of a requirement for NED-8 conjugation in metazoan development.

Amino Acid Sequence↗
PubMed2000

Physical activity surveillance in the 21(st) century.

PURPOSE: The 1996 Surgeon General's Report on Physical Activity and Health emphasized the health-related benefits of moderate-intensity physical activities, especially everyday activities. Unfortunately most surveillance systems in the U.S. primarily measure sports-related activities, particularly vigorous intensity sports. This report describes a new physical activity surveillance instrument designed to go beyond our current measures and include moderate-intensity everyday activities.METHODS: Data were collected from a nationally representative sample of adults (n = 5010). Questions were asked about occupational activity (mostly sitting; mostly walking; mostly heavy labor); walking (for exercise, transportation, or any other reason); moderate-intensity activities (brisk walking, yard work, vacuuming); vigorous-intensity activities (running, aerobics, heavy yard work); and strengthening activities (lifting weights, pull-ups, sit-ups). Questions included frequency and duration of activities. Respondents were defined as recommended if they participated in either moderate-intensity activities >/=30 min/day for >/=5 days/wk OR vigorous-intensity activities >/=20 min/day for >/=3 days/wk. Insufficient was defined as not meeting recommended levels while inactive was defined as no leisure-time activity.RESULTS: Overall 40% of adults were in the recommended group, 44% were in the insufficient group and 16% were inactive. Among working adults 37% had jobs that involved mostly walking or heavy labor and about 50% of those also were in the recommended group. Among the 63% of working adults who report mostly sitting at work, 39% were in the recommended group.CONCLUSIONS: These results suggest that measuring only leisure-time physical activity may under represent the physical activity experience of many U.S. adults. Broadening the concept of physical activity beyond traditional sports-related vigorous "exercise" may provide a more accurate picture of the prevalence of health-related physical activity.

Journal Article↗
PubMed2000

A Phase II trial of bryostatin-1 for patients with metastatic renal cell carcinoma.

BACKGROUND: Patients with metastatic renal cell carcinoma have a poor prognosis and no standard therapy is available. The authors performed a Phase II trial of the novel agent bryostatin-1 in this patient population. METHODS: In all, 30 patients with measurable, previously untreated metastatic renal cell carcinoma were studied. Patients had excellent physiologic reserve and preserved performance status. Bryostatin-1 (25 microg/m(2)) was given in the PET (polyethyleneglycol, ethanol, and Tween 80) formulation as a 30-minute intravenous infusion on Days 1, 8, and 15 of each 28-day cycle. In general, treatment was continued until disease progression. RESULTS: Two patients had significant objective responses, although methodologic problems made interpretation difficult. The median time to progression for all patients was 2.1 months; the median overall survival was 13.1 months. The treatment was generally well tolerated. Myalgia was the most common adverse event. One patient died while on study. This was a sudden death for a patient receiving a 15th cycle of therapy. Aside from this patient (for whom the correlation of study drug to death was not clear), no Grade 4 nonhematologic toxicity was encountered in more than 150 treatment courses delivered. CONCLUSIONS: There is minimal, if any, clinically relevant single-agent activity of bryostatin-1 at this dose and schedule for patients with metastatic renal cell carcinoma.

Adult↗
PubMed2000

Deterin, a new inhibitor of apoptosis from Drosophila melanogaster.

Deterin, a new apoptosis inhibitor from Drosophila melanogaster, possesses an unusual structure of only a single baculovirus inhibitor of apoptosis (IAP)-type repeat and no RING finger motif. The biochemical actions of deterin are demonstrated in SF9 and S2 cell transfection assays, in which the expressed protein acts in the cytoplasm to inhibit or deter cells from apoptosis otherwise induced by the caspase-dependent apoptosis activator reaper or by cytotoxicants. A loss of function phenotype for deterin of cell death was indicated by transfections with either a dominant negative deterin mutant or with inhibitory RNA (RNAi) for deterin. The dominant negative C-terminal fragment that antagonized antiapoptotic activity of deterin did not affect antiapoptotic activity of DIAP1 or p35. Both the baculovirus IAP-type repeat (BIR) domain and the alpha-helical C-terminal domain are necessary in both SF9 and S2 cells for deterin to manifest its activity to prevent cell death. The approximately 650-base deterin transcript is present in embryos, third instar larvae, and late stage nurse cells of adult females. The deterin transcript is distributed throughout early stage embryos, whereas in later stage embryos it becomes progressively restricted to the central nervous system and gonads. Whereas the nematode survivin-type IAP has thus far been implicated only as a mitotic regulator, Drosophila deterin constitutes the first invertebrate member of the survivin-type IAP group to exhibit apoptosis-inhibitory activity.

Amino Acid Sequence↗
PubMed2000

Expression pattern of T-cell-associated chemokine receptors and their chemokines correlates with specific subtypes of T-cell non-Hodgkin lymphoma.

Chemokine receptors mediate the migration of lymphocytes through the binding of soluble ligands, and their expression is differentially regulated in lymphocyte subsets. The pattern of chemokine receptor expression in T-cell non-Hodgkin lymphoma has not been previously studied. Using a panel of mouse monoclonal antibodies, we studied the immunohistochemical expression of the Th1-associated chemokine receptor CXCR3 in 141 patients with T-cell lymphoma, and we studied the receptors CCR4 and CCR5 and some of their ligands in a subset of these tumors. Expression of CXCR3 was typical of the smaller T cells in angioimmunoblastic lymphoma (15 of 18 patients), angiocentric lymphoma (3 of 3 patients), histiocyte-rich tumors (4 of 5 patients), and unspecified T-cell lymphomas (17 of 39 patients). CXCR3 expression was seen in only 1 of 15 patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma. In contrast, all ALK-positive tumors showed diffuse reactivity for the Th2-associated receptor CCR4 (5 of 5 patients). CCR4 expression was also a consistent feature of the large-cell transformation of mycosis fungoides. CCR5 expression showed no consistent association with any T-cell tumor type. The chemokines Mig (CXCR3 ligand), TARC (CCR4 ligand), and MCP-2 (CCR5 ligand) were detected in intratumoral blood vessels and histiocytes. Mig was also coexpressed by a subset of CXCR3-positive tumor cells in 6 of 20 lymphomas. MCP-2 was highly expressed in stromal cells in 3 patients with nodal involvement by cutaneous T-cell lymphoma. As with normal T-cell subsets, we demonstrated that there is frequent differential expression of chemokine receptors in T-cell tumors, which may explain, in part, the distinctive patterns of spread in different tumor subtypes. (Blood. 2000;96:685-690)

Anaplastic Lymphoma Kinase↗
PubMed2000

Distinctive structural and kinetic properties of an unusual juvenile hormone-hydrolyzing esterase.

The insect juvenile hormone specific esterases (JHEs), related to acetylcholinesterases but exhibiting substrate specificity for juvenile hormone (JH), are essential enzymes for normal insect development, making them attractive targets for biorationally designed, environmentally safe pesticides. We examine here a new enzyme, JHER, related to, but yet structurally, biochemically, and kinetically distinct from, the classical JHE. Both classical JHE and baculovirus-expressed JHER hydrolyze JH show disproportionately higher catalytic rates at higher substrate concentrations (in contrast to substrate inhibition reported for acetylcholinesterase) and are similarly inhibited by an organophosphate. However, JHER, which possesses an unusual cysteine residue at +1 to the catalytic serine, is less sensitive to trifluoromethyl ketone transition state analogs designed around the structure of JH. We propose a model in which JHER is expressed just prior to metamorphosis for hydrolysis of a JH-like substrate with hydrophobic backbone, a proximal ester, and a terminal expoxide or related substitution.

Amino Acid Sequence↗
PubMed2000

Use of rifabutin with protease inhibitors for human immunodeficiency virus-infected patients with tuberculosis.

Drug interactions between rifamycins and highly active antiretroviral therapy (HAART) have raised concerns in the treatment of human immunodeficiency virus (HIV)-infected patients with tuberculosis. We conducted a study of this interaction by measuring serum drug levels of all HIV-infected patients with tuberculosis who were admitted to A. G. Holley State Tuberculosis Hospital (Florida) from October 1997 through December 1998, who were concomitantly treated with rifabutin and HAART. All 25 patients studied became culture-negative within 2 months of initiation of therapy for tuberculosis and remained negative for a median of 13 months follow-up after completion of therapy. HIV viral loads (mean+/-SEM) decreased significantly from 4.95+/-0.21 log10 copies/mL before initiation of HAART to 2.77+/-0.07 log10 copies/mL before discharge (P<.001); 20 of 25 patients achieved viral loads of <500copies/mL. In summary, the concomitant use of rifabutin and HAART can lead to successful treatment of HIV-infected patients with tuberculosis without increased side effects.

Adult↗
PubMed2000

Recombinant human thrombopoietin attenuates carboplatin-induced severe thrombocytopenia and the need for platelet transfusions in patients with gynecologic cancer.

BACKGROUND: Thrombocytopenia is a significant problem in the treatment of cancer. OBJECTIVE: To assess the clinical safety of therapy with recombinant human thrombopoietin (rhTPO) and its ability to ameliorate chemotherapy-induced severe thrombocytopenia. DESIGN: Phase I/II clinical cohort study. SETTING: The University of Texas M.D. Anderson Cancer Center, Houston, Texas. PATIENTS: 29 patients with gynecologic cancer. INTERVENTION: Recombinant human thrombopoietin was given before chemotherapy and after a second cycle of carboplatin therapy. MEASUREMENTS: Peripheral blood counts and platelet transfusions. RESULTS: Administration of rhTPO after chemotherapy significantly reduced the degree and duration of thrombocytopenia and enhanced platelet recovery. In patients who received the optimal biological dose of rhTPO (1.2 microg/kg of body weight) in cycle 2 (carboplatin plus rhTPO), the mean platelet count nadir was higher (44x10(9) cells/L and 20x10(9) cells/L; P = 0.002) and the duration of thrombocytopenia was shorter (days with a platelet count <20x10(9) cells/L, 1 and 4 [P = 0.002]; days with a platelet count <50x10(9) cells/L, 4 and 7 [P = 0.006]) than in cycle 1 (carboplatin only). The need for platelet transfusion in this group was reduced from 75% of patients in cycle 1 to 25% of patients in cycle 2 (P = 0.013). CONCLUSIONS: Therapy with rhTPO seems to be safe and may attenuate chemotherapy-induced severe thrombocytopenia and reduce the need for platelet transfusions.

Analysis of Variance↗
PubMed2000

Regulation of the juvenile hormone esterase gene by a composite core promoter.

Transcription from the core promoter of the juvenile hormone esterase gene (-61 to +28) requires the presence of both an AT-rich motif (TATA box) and an initiator motif for any transcription to occur, when assayed by either transcription in vitro with lepidopteran Sf9 nuclear extracts or by transient-transfection assay in Sf9 cells. Additional gel-shift experiments indicated that at least one additional binding site is essential for transcription to occur. Mutational analysis in the transcription-in vitro and cell-transfection assays demonstrated that a 14-bp region from +13 to +27 relative to the transcription start site is also essential for transcription to occur. Whereas the wild-type core promoter is highly transcriptionally active, inclusion of additional flanking sequences to position -212 reduces that activity approx. 100-fold, and inclusion of the 5' region out to position -500 reduces transcription by 200-fold. The pattern of dependence on both the AT-rich motif and the initiator for detectable transcription, and the high innate activity being repressed by 5'-binding factors, was recapitulated in mosquito C7-10 cells. This study demonstrates that the cellular juvenile hormone esterase gene is organized as a composite core promoter, dependent on both TATA-box and initiator-binding factors, an organization that has been more commonly reported for viral promoters. This highly active composite core promoter is made more complex by the absolute dependence on the presence of a third site shortly downstream from the initiator, which is distinct from the 'downstream promoter element' described from some TATA-less genes. The juvenile hormone esterase gene thus appears to be a model of a cellular composite core promoter with a multipartite, indispensible requirement for not just both the TATA box and initiator, but also for at least a third core element as well.

Animals↗
PubMed2000

The chemokine receptor CXCR3 is expressed in a subset of B-cell lymphomas and is a marker of B-cell chronic lymphocytic leukemia.

Chemotaxis in leukocytes is mediated through binding of soluble chemokines to transmembrane G-protein coupled receptors. The chemokine receptor CXCR3 has been previously shown to be widely expressed on activated T cells and to mediate T-cell chemotaxis on binding to various ligands, including Mig, IP-10, and ITAC. By using immunohistochemical and flow cytometric analysis, we report that CXCR3 is also expressed on a subset of peripheral blood B cells and in distinct subtypes of B-cell lymphoma. CXCR3 immunohistochemical or flow cytometric expression was seen in 37 of 39 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (diffusely positive in 33 cases), whereas mantle cell lymphoma (30 cases), follicular lymphoma (27 cases), and small noncleaved cell lymphoma (8 cases) were negative in all but 2 cases. Strong CXCR3 expression was also seen in splenic marginal zone lymphoma (14 of 14 cases) and in the monocytoid and plasmacytic cells in extranodal marginal zone lymphoma (15 of 16 cases). This differential expression of CXCR3 in B-cell tumors contrasts with that of another B-cell-associated chemokine receptor, BLR1/CXCR5, which we show here is expressed on all types of B-cell lymphoma tested. We also report that the CXCR3 ligand, Mig, is coexpressed on tumor cells in many cases of CLL/SLL (10 of 13 cases examined) with Mig expression less frequently seen in other B-cell lymphoma subtypes. Coexpression of CXCR3 and its ligand, Mig, may be an important functional interaction in B-CLL, as well as a useful diagnostic marker for the differential diagnosis of small cell lymphomas. (Blood. 2000;95:627-632)

B-Lymphocytes↗
PubMed2000

Efficacy of postoperative follow-up telephone calls for patients who underwent adenotonsillectomy.

OBJECTIVE: To evaluate the efficacy and cost-effectiveness of postoperative follow-up telephone calls among pediatric patients who underwent adenotonsillectomy. DESIGN: Prospective study with a follow-up questionnaire administered by telephone. SETTING: Tertiary-care children's hospital. PATIENTS: One hundred thirty-four children between the ages of 4 and 18 years who underwent adenotonsillectomy between December 1997 and June 1998 and did not have associated cardiac, pulmonary, bleeding, or syndromic disorders were included in this pilot study. INTERVENTION: Parents of these patients were given the opportunity to participate in our study, and it was emphasized that, at any time during the child's care, if the parent desired a follow-up visit or if the child experienced any symptoms that caused concern, the parent should contact the clinic for a follow-up appointment. A telephone call was placed 3 to 4 weeks postoperatively by an otolaryngology nurse, and a questionnaire was filled out using the parents' responses. MAIN OUTCOME MEASURES: The incidence rates of voice change, velopharyngeal insufficiency, bleeding, constipation, dehydration, and pain were measured. Parent satisfaction, patient safety, and cost-benefit were also evaluated. RESULTS: Less than 5% of patients reported temporary velopharyngeal insufficiency, while 2% of patients required operative intervention for bleeding episodes and 1% required hospitalization. Voice change, reported by approximately 70% of all patients, was the most common complaint, but it resolved in all instances. Pain was reported to be most severe on postoperative day 1. Ninety-six percent of parents requested no further follow-up visit. CONCLUSIONS: Our pilot study revealed that a follow-up telephone call is a safe and cost-effective method of postoperative management for pediatric patients who have undergone adenotonsillectomy and that this method of follow-up is also desirable to parents.

Adenoidectomy↗
PubMed2000

Effect of asthma on the quality of life among children and their caregivers in the Atlanta Empowerment Zone.

BACKGROUND AND OBJECTIVE: Asthma is the most common chronic pediatric disease and exacts a toll on the health-related quality of life of affected children and their primary caregivers. This investigation describes the relationship between the clinical severity of asthma among inner-city children and their quality of life and that of their primary adult caregivers. METHODS: Telephone interview data were collected from individual adult caregivers of 5-12-year-old children with asthma. Questions addressed the history, diagnosis, and management of the child's asthma, the child's family and social background, the family's socioeconomic status, the caregiver's knowledge and attitude about asthma, and the health-related quality of life of both the child and the caregiver. An asthma severity score was calculated from the caregiver's responses to questions about their child's wheezing frequency, nocturnal and early morning symptoms, and speaking during an asthma attack, as well as the impact of the disease on their child's physical activity and breathing during the prior 4-month period. A clinical asthma triage score was determined from information collected at the emergency department about the child's oxygen saturation, alertness, use of accessory respiratory muscles, extent of breathlessness, and peak expiratory flow. Spearman correlation coefficients were used to identify association between quality of life and disease severity, caretaker's asthma knowledge, and functional impact of asthma symptoms. RESULTS: Data from 240 of 755 eligible children were analyzed. Most children were younger than 11 years, male, black, and non-Hispanic. The children's median duration of asthma diagnosis was 86% of their life (range less than 1 to 11.3 years, median 5.0 years). Of the primary caregivers, 69% had at least completed high school, and 90% reported a total monthly household income of $1,600 or less. The maximum possible quality-of-life score and the median for caregivers were 91 and 70, respectively; for children, the same scores were 69 and 58, respectively. In addition, there was significant negative correlation of the quality-of-life scores of both the caregivers and children with the number of schooldays the children missed (r = -0.24 and r = -0.26, respectively, P < .001 for both) and the caregivers' and children's asthma severity scores (r = -0.39 and r = -0.47, respectively, P < .001 for both). The quality-of-life scores of the children and caregivers did not correlate significantly with the asthma triage scores. CONCLUSIONS: The questionnaires captured baseline quality-of-life information about this urban population and will facilitate longitudinal monitoring. The fact that the quality-of-life scores of children with asthma correlated with those of their adult caregivers, but not with their clinical triage scores, highlights the impact of asthma on families and the importance of having a long-term comprehensive management plan that is not based on exacerbations, but that includes both the children and their primary caregivers.

Asthma↗
PubMed2000

Consequences of delay in surgical treatment of biliary disease.

BACKGROUND: Delay of laparoscopic cholecystectomy after the diagnosis of uncomplicated biliary disease is common at our institution. This study assessed the effect of delay of operation for symptomatic biliary disease. METHODS: A cohort of 251 patients was retrospectively reviewed at Parkland Memorial Hospital with follow-up available for 168 patients (67%) from January 1998 to July 1998. Data were analyzed using Student's t test and the chi-square test. RESULTS: Of the 88 patients with the initial diagnosis of biliary colic, 69 (78%) underwent elective laparoscopic cholecystectomy. Thirty-six patients made a total of 44 return visits the emergency department with a recurrent attack of biliary colic or a complication of gallstone disease. Mean operative time increased from 94 minutes for elective operations to 122 minutes for nonelective operations and hospital stay increased from 0.6 days to 6.1 days. Conversion to open operation increased from 6% in the elective group to 26% in the nonelective group. CONCLUSION: Delay of surgical therapy is associated with complications, increased operative times, higher conversion to open cholecystectomy, and prolonged hospitalization. We conclude that patients with symptomatic cholelithiasis should undergo early cholecystectomy.

Adult↗
PubMed2000

Transfer of methohexital across the perfused human placenta.

STUDY OBJECTIVES: To evaluate the transfer properties of methohexital and the influence of protein binding using the in vitro human placental perfusion model. DESIGN: Fresh term human placentae from healthy parturients were perfused bidirectionally via a cannulated fetal chorionic artery and vein and needles placed into the maternal intervillous space. Maternal-to-fetal (M-->F) and fetal-to-maternal (F-->M) transfer and ultimate distribution of methohexital was investigated using a closed (recirculating) placental perfusion model. SETTING: Obstetric anesthesia laboratories of two university medical centers. PATIENTS: No patient participation occurred as placentae were obtained after delivery. INTERVENTION: M-->F and F-->M transfer of methohexital was compared in vitro in perfusates with equal protein concentrations (2 g/100 mL in both perfusates) or albumin-simulated physiologic protein binding concentrations (maternal 8 g/100 mL; fetal 4 g/100 mL). MEASUREMENTS AND MAIN RESULTS: Data obtained consisted of measurements of methohexital and antipyrine concentrations by high-performance liquid chromatography. Glucose and lactate concentrations and perfusate loss were measured to assess placental viability. Methohexital protein binding was assessed at 2, 4, and 8 g/100 mL of albumin by equilibrium dialysis. The transfer index of 0.83 +/- 0.11 for the M-->F perfusions was significantly greater (p < or = 0.05) than in the F-->M direction (0.61 +/- 0.04) when albumin concentration was equal in both perfusates. This transfer asymmetry disappeared when albumin concentrations simulating maternal (8 g/100 mL) versus fetal (4 g/100 mL) protein concentrations in the perfusate were used (M-->F 0.87 +/- 0.12 and F-->M 0.95 +/- 0.11). CONCLUSION: Methohexital readily crosses the placenta in both directions. Protein binding has significant effects on the degree of transfer of methohexital at any time when compared with antipyrine and its ultimate fetal/maternal distribution.

Adolescent↗