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Biomedical subjects

D Jones

Publications and source records attributed to D Jones.

At least 325 records · Page 18Linked to original sources

Transgenic strains of the nematode C. elegans in biomonitoring and toxicology: effects of captan and related compounds on the stress response.

The fungicide, captan, induces a cellular stress response in the soil nematode Caenorhabditis elegans. Transgenic C, elegans, which produce beta-galactosidase as a surrogate stress protein, reveal that captan-induced stress is localized mainly to muscle cells of the pharynx. The stress response is elicited by captan concentrations above 5 ppm and occurs within five hours of the initial exposure to the fungicide. Higher concentrations of captan, up to the solubility limit, increase the intensity of the response. Adult nematodes are significantly more sensitive to captan than are larvae. Captan also inhibits feeding in C. elegans, and nematodes exposed to captan rapidly cease muscular contractions in the pharynx. Stress induction and feeding inhibition are also caused by the related fungicides, captafol and folpet, but not by the parent compounds, phthalimide and tetrahydrophthalimide. The inhibition of feeding caused by compounds which elicit the cellular stress response may be an important survival mechanism for C, elegans.

Animals↗

A community trial of a written self management plan for children with asthma. Asthma Foundation of NZ Children's Action.

AIMS: To determine the effect of introducing an action plan to children with mild to moderate asthma, who have never used a plan before. METHODS: Children were recruited from general practitioner records with a diagnosis of asthma, and who agreed to participate, having identified that they had not used an action plan before and that they had mild or moderate asthma based upon symptoms, acute episodes and the need for preventative medication. The families were given a plan, and its use was explained to them by their general practitioner. A symptom diary was kept, and, where appropriate, peak flow measurements were recorded. A number of outcomes were measured to determine changes that could be attributed to the introduction of the plan. RESULTS: Following the introduction of the plan, the percentage of nights woken for asthma fell from 18.2% to 12.2% (P<0.001) and the number of days out of action fell from 6.4 to 4.1 (P<0.001). The requirement for acute medical treatment also fell during the intervention period with general practitioner visits falling from 129 to 42 (p<0.001). Most participants commented favourably about the usefulness of the plan in giving them a better idea of the state of their asthma at any time, and in knowing what to do about it. CONCLUSIONS: The children's action plan, when introduced into a group of asthmatic children was effective and acceptable in the self management of asthma.

Asthma↗

Activated Ras displaces 14-3-3 protein from the amino terminus of c-Raf-1.

The serine/threonine protein kinase c-Raf-1 interacts with a number of cellular proteins including 14-3-3 isoforms which may be regulators or substrates of c-Raf-1 in signal transduction pathways. In vivo and in vitro binding analyses of c-Raf-1 and mutant proteins with 14-3-3 zeta indicate bivalent binding of 14-3-3 zeta to the amino terminus as well as to the carboxy terminus of c-Raf-1. Although 14-3-3 zeta and Ras use different binding regions on the amino terminal regulatory domain of c-Raf-1 (c-Raf-NT), 14-3-3 zeta is displaced from the amino terminus upon binding of activated Ras. In contrast, if c-Raf-1 full length is analysed instead of the separately expressed c-Raf-NT, binding of 14-3-3 zeta is only slightly effected by co-expression of activated Ras. This is explained by a second binding site of 14-3-3 zeta at the carboxy terminus of c-Raf-1. The mutant c-Raf-NT (S259A) cannot bind 14-3-3 zeta, suggesting a regulatory role of this in vivo phosphorylation site. However, c-Raf-NT phosphorylated or unphosphorylated at S259, is able to bind 14-3-3 zeta. Even though 14-3-3 zeta can be phosphorylated in vivo, only the unphosphorylated form binds to the amino terminus of c-Raf-1. The data presented indicate, that 14-3-3 zeta binds to c-Raf-1 in a bivalent fashion in unstimulated cells. 14-3-3 zeta is displaced from the amino terminus but not from the carboxy terminus of c-Raf-1 by binding of activated Ras to c-Raf-1.

14-3-3 Proteins↗

Crystallization of a 14-3-3 protein.

Crystals of the tau (tau) isoform of the 14-3-3 family of proteins were grown and shown to belong to the orthorhombic space group P2(1)2(1)2(1) with cell dimensions a = 70.29, b = 79.3, c = 101.00 A. The crystals were needle-like in morphology and less than 10 micro m in two dimensions. Diffraction data were collected using synchrotron radiation sources from flash-cooled crystals. Native data extended to a resolution of 2.6 A and mercury and platinum derivatives diffracted to 3.4 and 3.9 A, respectively. The structure has been solved recently. Here the protein crystallization procedures, the characterization of the crystals and the correlation between crystal habit and diffraction quality are reported.

Journal Article↗

Der(16)t(1;16)(q21;q13) in Wilms' tumor: friend or foe.

The der(16)t(1;16)(q21;q13) chromosomal abnormality has been reported rarely in Wilms' tumor. This abnormality has also been found in several other pediatric and adult neoplasms, and may imply a poor prognosis in at least some of these solid tumors. To investigate its clinical significance in Wilms' tumor, we examined the records of 65 consecutive children with Wilms' tumor whose tumor cells were successfully karyotyped. The t(1;16) was present in seven patients (10%) whose ages ranged from 2.5 to 4.7 years (median 3.5 years) at diagnosis. Six of the seven patients were female. All four stages of Wilms' tumor were represented (two patients had stage IV disease). No patient had bilateral disease. All tumors were of "favorable histology." All seven patients are alive and off therapy with a median follow-up of 3.2 years (range, 2 to 8.5 years). One patient with this abnormality developed brain metastases within 4 months of completion of therapy. Comparison of these patients with the remaining 58 Wilms' tumor patients revealed no significant differences with regard to disease stage, histology, survival, or relapse-free survival. Cytogenetic evidence of der(16)t(1;16)(q21;q13) in Wilms' tumor does not appear to portend an adverse clinical outcome, although only a larger study that includes molecular detection methods can provide more conclusive evidence.

Child↗

Altered hexamerin regulation in prepupal Trichoplusia ni pseudoparasitized by Chelonus sp. near curvimaculatus.

Adult female wasps of species in the subfamily Cheloninae inject an egg, venom, polydnavirus and other materials into the host egg during oviposition. Hosts then exhibit precocious expression of the metamorphic developmental program, but then further development by the precocious prepupa is suppressed. These effects occur in truly parasitized hosts (those that contain a live endoparasite larva) as well as in pseudoparasitized hosts (that do not contain a live endoparasite). We report here that during the precocious prepupal stage, the hexamerins BJHSP1 and BJHSP2 persist in the hemolymph of pseudoparasitized hosts, whereas in normal larvae these proteins are cleared from the hemolymph in response to the normal surge in prepupal ecdysteroids. Northern blot analysis of poly(A) RNA showed that the basis for this persistence is not an abnormally high abundance of the transcripts on the day following wandering in pseudoparasitized larvae. Nor is the source of the hexamerins the parasite larva, for it is missing from the pseudoparasitized hosts. The hypothesis that the persistence is due to a suppressed titer of ecdysteroids in pseudoparasitized hosts (reported earlier: [jones et al., Arch Insect Biochem Physiol 21:155 (1992)] was tested by use of a large size variant of pseudoparasitized hosts in which the prepupal ecdysteroid titer is partially restored by endogenous ecdysteroid production. In such pseudoparasitized prepupae, the two hexamerins were cleared from the hemolymph on the day following host wandering behavior, as in normal larvae. Thus, the regulatory basis of the persistence of the hexamerins BJHSP1 and BJHSP2 in the hemolymph of pseudoparasitized hosts appears to be at the posttranslational level, with suppression of the prepupal ecdysteroid titer causing omission of the normal trigger for fat body uptake of the hexamerins.

Animals↗

Vinyl chloride loss during laboratory holding time.

Because vinyl chloride is a potent human carcinogen, it is important that analytical results from groundwater samples accurately reflect levels of exposure to groundwater users. This study investigated the current allowable holding time of 14 days to determine if vinyl chloride is lost from samples during this time. Samples containing an initial concentration of 2 microg/liter of vinyl chloride showed progressive, increasing losses when held for 1, 2, 7, and 14 days. Due to the inherent variability of low-level laboratory results, the most statistically significant loss (alpha = 0.05) was seen for samples held for 14 days. No statistically significant differences in degradation pattern were noted between analytical detectors used (PID versus Hall) or sample type (lab versus field). There also was a loss of vinyl chloride observed during sample collection and handling. These results suggest that analytical variability at low concentrations and the establishment of health-based guidelines near the analytical detection limit require multiple samples be collected from a single location when highly accurate results are needed. These findings should be considered in public health exposure assessments and the implementation of health-based recommendations at sites with vinyl chloride groundwater contamination.

Carcinogens↗

Structure and experimental uses of arthropod venom proteins.

In summary, the initial studies conducted thus far into the components of venoms of parasitic wasps and other arthropods have already yielded a number of interesting properties of the proteins therein. These properties have already offered the possibilities of additional principles operating in the evolution of venoms. That so many unexpected rewards have already surfaced with the relatively little experimental digging conducted thus far generates great anticipation that indeed there remains a pharmacological gold mine awaiting to be discovered in components of the other insect venoms as yet unmined by science.

Amino Acid Sequence↗

Transgenic Caenorhabditis elegans strains as biosensors.

Toxicity bioassays rely largely on lethality measurements. Such assays are generally lengthy and expensive, and provide little information on mechanisms of toxicity. A desire to understand the mechanisms by which cells respond to physical and chemical stresses has led to interest in measuring stress proteins as toxicological endpoints. Transgenic strains of the nematode Caenorhabditis elegans that carry a reporter enzyme under control of a stress-inducible promoter have been created. The reporter is easily quantified in intact nematodes, and it responds to a wide range of chemical stressors. Therefore, transgenic C. elegans can provide the basis for a wide range of quick, simple and informative bioassays.

Animals↗

The incidence of multiple gestations after in vitro fertilization is dependent on the number of embryos transferred and maternal age.

OBJECTIVE: To determine if the incidence of multiple gestations after IVF differs significantly depending on the number of embryos transferred and maternal age. DESIGN: Retrospective analysis of IVF database. SETTING: Tertiary care academic center. PATIENTS: One thousand eight hundred sixty-seven patients undergoing IVF with up to four embryos transferred during 1986 through 1993. MAIN OUTCOME MEASURES: The rate of singleton and multiple gestations > 20 weeks estimated gestational age (EGA). RESULTS: The incidence of triplet gestations > 20 weeks EGA among patients < or = 34 years of age with three versus four embryos transferred was 0.3% (1/335) versus 2.4% (15/662), respectively. The incidence of twin gestations > 20 weeks EGA among patients < or = 34 years of age with two versus four embryos transferred was 1.3% (3/234) versus 7.4% (46/622), respectively. Also among patients < or = 34 years of age, the incidence of singleton gestations > 20 weeks EGA with two versus three embryos transferred was 12.8% (30/234) versus 15.8% (53/335); with two versus four embryos was 12.8% (30/234) versus 17.2% (107/622); and with three versus four embryos was 15.8% (53/335) versus 17.2% (107/622), respectively. CONCLUSIONS: In women < or = 34 years of age undergoing IVF-ET, the transfer of four versus three and four versus two embryos significantly increased the incidence of triplet and twin gestations, respectively, without significantly improving the chance of singleton conception. This implies that a policy of transferring only three embryos should be considered in this age group (realizing that such a policy may merit modulation if pretransfer embryo selection is used.).

Adult↗

A comparison of two noninvasive methods of blood pressure measurement in the triage area.

OBJECTIVE In triage of patients in the emergency department, nurses can identify conditions such as elevated blood pressure that can lead to serious health problems. It is imperative that the method used to evaluate blood pressure is dependable and accurate. The introduction of new technology may yield results that are not comparable to traditional measures. Therefore we compared the traditional auscultatory method of measuring blood pressure with the use of an automated device. METHODS The blood pressure of 100 healthy adult volunteers was measured first with the traditional cuff method and then with an automated device (IVAC model 4200). The measurements were recorded and then compared for each individual. RESULTS The mean difference between the paired systolic measurements was 4.3 mm Hg (p = 0.0001). The mean difference between the paired diastolic measurements was 1.3 mm Hg. There was a clinically significant difference (> 9 mm Hg) in 37% of the systolic readings and 26% of the diastolic readings. In 76% of those clinically significant systolic differences, the IVAC 4200 measurement exceeded the manual method. For the clinically significant diastolic differences, 58% of the IVAC 4200 measurements were greater than the manual method. CONCLUSION Clinicians must be cautious when using new technology to measure blood pressure. Results may not be comparable with results obtained with the traditional method.

Adolescent↗

Proton dosimetry intercomparison.

BACKGROUND AND PURPOSE: Methods for determining absorbed dose in clinical proton beams are based on dosimetry protocols provided by the AAPM and the ECHED. Both groups recommend the use of air-filled ionization chambers calibrated in terms of exposure or air kerma in a 60Co beam when a calorimeter or Faraday cup dosimeter is not available. The set of input data used in the AAPM and the ECHED protocols, especially proton stopping powers and w-value is different. In order to verify inter-institutional uniformity of proton beam calibration, the AAPM and the ECHED recommend periodic dosimetry intercomparisons. In this paper we report the results of an international proton dosimetry intercomparison which was held at Loma Linda University Medical Center. The goal of the intercomparison was two-fold: first, to estimate the consistency of absorbed dose delivered to patients among the participating facilities, and second, to evaluate the differences in absorbed dose determination due to differences in 60Co-based ionization chamber calibration protocols. MATERIALS AND METHODS: Thirteen institutions participated in an international proton dosimetry intercomparison. The measurements were performed in a 15-cm square field at a depth of 10 cm in both an unmodulated beam (nominal accelerator energy of 250 MeV) and a 6-cm modulated beam (nominal accelerator energy of 155 MeV), and also in a circular field of diameter 2.6 cm at a depth of 1.14 cm in a beam with 2.4 cm modulation (nominal accelerator energy of 100 MeV). RESULTS: The results of the intercomparison have shown that using ionization chambers with 60Co calibration factors traceable to standard laboratories, and institution-specific conversion factors and dose protocols, the absorbed dose specified to the patient would fall within 3% of the mean value. A single measurement using an ionization chamber with a proton chamber factor determined with a Faraday cup calibration differed from the mean by 8%. CONCLUSION: The adoption of a single ionization chamber dosimetry protocol and uniform conversion factors will establish agreement on proton absorbed dose to approximately 1.5%, consistent with that which has been observed in high-energy photon and electron dosimetry.

Calibration↗

High-avidity human IgG kappa monoclonal antibodies from a novel strain of minilocus transgenic mice.

Human immunoglobulin transgenic mice provide a method of obtaining human monoclonal antibodies (Mabs) using conventional hybridoma technology. We describe a novel strain of human immunoglobulin transgenic mice and the use of this strain to generate multiple high-avidity human sequence IgG kappa Mabs directed against a human antigen. The light chain transgene is derived in part from a yeast artificial chromosome clone that includes nearly half of the germline human V kappa region. In addition, the heavy-chain transgene encodes both human mu and human gamma 1 constant regions, the latter of which is expressed via intratransgene class switching. We have used these animals to isolate human IgG kappa Mabs that are specific for the human T-cell marker CD4, have high binding avidities, and are immunosuppressive in vitro. The human Mab-secreting hybridomas display properties similar to those of wild-type mice including stability, growth, and secretion levels. Mabs with four distinct specificities were derived from a single transgenic mouse, consistent with an extensive diversity in the primary repertoire encoded by the transgenes.

Animals↗

Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro.

Leukaemic cells from most cases of B-chronic lymphocytic leukaemia die rapidly by apoptosis in vitro unless they are cultured in the presence of interleukin-4 or interferon alpha or gamma. We now report prolonged survival of purified CLL cells cultured on bone marrow (BM) derived stromal cells in the absence of exogenous growth factors. In 10 cases of CLL examined 0-61% (mean 14.7%) of the cells were viable after 10 d culture in medium alone, whereas in the presence of BM stromal cells 10-102% (mean 47.0%) of cells were recovered alive (P < 0.005) in 7/10 cases of CLL, cells remained viable after 30 d of culture in BM stromal cells with cell recovery of 12-65%. These long-term cultured CLL cells were Epstein Barr virus negative, shown by the failure to detect the ENBA-2 and BZLF1 genes of EBV by PCR analysis. Identity between day 0 and day 30 CLL cells was demonstrated by sequence analysis of their clonal IgH CDR3 region. Adherence of CLL cells to BM stromal cell layers was critical for their protection from apoptosis. Separation of CLL cells from stroma by 0.45 micron culture filters resulted in loss of the protective effect of the stromal cells. Stromal cells were also able to protect CLL cells from hydrocortisone-induced apoptotic cell death. Our findings provide an in vitro system that can be used to analyse the growth requirements of CLL cells and their chemosensitivity in an in vitro environment that mimics the in vivo milieu.

Aged↗

Direction of report in spatial and verbal serial short-term memory.

Four experiments examined the role played by item and order information in determining the effects of order of report of a sequence from short-term memory. Experiments in which list items were re-presented prior to recall so that only their order had to be reported showed no differences in performance between the forward and backward direction of report. This result was found with lists of auditory-verbal, visual-verbal, and spatial stimuli. When the list items were not re-presented, so that recall of both items and order was required, recall in the backward direction of report was significantly worse than in the forward direction of report, both in spatial and verbal tasks. The results point to the symmetry of inter-item associations, though only equivocally so, but they suggest strongly that the processes of spatial and verbal serial recall share many functional characteristics.

Adult↗

Cytologic diagnosis of primary serous lymphoma.

Lymphomas arising primarily in serosal surfaces have recently been described. Although these "body-cavity" lymphomas usually present as an effusion, the role of cytologic diagnosis has not been fully explored. The authors present seven cases of primary serous lymphoma. All were large cell lymphomas (5 B cell types, 2 T cell types). Three distinct clinical presentations were seen. Four patients had the rapid onset of pleural effusions without an associated mass in the setting of immunodeficiency (3 with AIDS, 1 with Castleman's disease). Cytologic examination of the effusion was positive in all cases for B-cell lymphoma. All four patients died of their disease in less than 6 months. Two other patients with AIDS and T-cell lymphomas both of which were associated with a serosal mass as well as an effusion. Although cytologic examination revealed numerous atypical lymphoid cells, clonality could not be demonstrated. One patient survived for more than 1 year, the other lymphoma was an incidental finding at autopsy. Finally, one B-cell lymphoma arose in a patient with chronic pleuritis. Pleural decortication was required to identify the neoplastic cells. The authors conclude that primary serosal lymphomas have characteristic clinical presentations, and that although cytologic and flow cytometric examination of effusions is necessary for the diagnosis of immunodeficiency associated B-cell lymphomas, tissue biopsy will likely be required in patients with immunodeficiency-associated T-cell lymphomas or lymphomas associated with chronic pleuritis.

Acquired Immunodeficiency Syndrome↗