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Biomedical subjects

E Jones

Publications and source records attributed to E Jones.

At least 145 records · Page 8Linked to original sources

Cloning and expression of FECV spike gene in vaccinia virus. Immunization with FECV S causes early death after FIPV challenge.

The spike gene of the feline enteric coronavirus (FECV), strain FECV-1683, was PCR amplified from total RNA extracted from FECV-infected cells and its sequence determined. A primary translation product of 1454 amino acids is predicted from the nucleotide sequence, containing a N-terminal signal sequence, a C-terminal transmembrane region and 33 potential N-glycosylation sites. The sequence shares 92% homology with the previously published feline infectious peritonitis virus, strain WSU-1146; however, several regions were identified that distinguished FECV from Feline Infectious Peritonitis virus, FIPV. The full length FECV S gene was cloned and expressed in vaccinia virus. Recombinants produced a 200 kD protein which was recognized by sera from cats infected with FIPV. When kittens were immunized with the vaccinia/FECV S recombinant, neutralizing antibodies to FIPV were induced. After challenge with a lethal dose of FIPV, the recombinant vaccinated animals died earlier than control animals immunized with vaccinia virus alone.

Animals↗

Molecular cytogenetic analysis of a t(7;10) in a human glioblastoma cell line.

Glioblastoma multiforme (GBM) is the most malignant glial brain tumor in humans. The fact that deleted copies of chromosome 10 are observed frequently in primary GBM tumors supports the hypothesis that one or more tumor suppressor genes located on chromosome 10 occupy crucial growth control checkpoints for glial cells. Deletion mapping in primary GBM tumors using the loss of heterozygosity (LOH) test has implicated the 10q24-10qter region as one possible site for a gene. We report here on the molecular cytogenetic analysis of chromosome 10 abnormalities in a human GBM cell line, JBSA. LOH testing showed that JBSA cells were hemizygous for chromosome 10. Molecular cytogenetic analysis showed that the undeleted homologue was involved in a reciprocal translocation t(7;10)(p21;q22). The translocation breakpoint on chromosome 10 lay within band q22 between D10S19 and D10S4. The fact that JBSA cells lack one homologue of chromosome 10 and carry a translocation breakpoint on the remaining one, proximal to the smallest region of overlap reported in primary tumor deletions, suggests that 10q22 may be another possible site for a tumor suppressor gene involved in GBM.

Brain Neoplasms↗

Homologous centromere association of chromosomes 9 and 17 in prostate cancer.

Chromosomal loss in cancer cells has been observed by nonisotopic in situ hybridization using pericentromeric probes. Accurate determination of this loss depends upon efficient hybridization and visualization of all probe signals in a two-dimensional field. Close association of homologous centromeres, reported in various normal and tumor tissues, can complicate evaluation and interpretation, resulting in the overestimation of actual chromosome loss. Using pericentromeric FISH probes for chromosomes 9 (classical and beta-satellite) and 17 (alpha-satellite), as well as 17q-specific phage probes, we tested the frequency of homologous centromere association in normal and malignant prostate tissues and lymphoblastoid cells. We found that the pericentromeric region of both chromosome 9 and 17 associated in prostate tissues, but only chromosome 9 demonstrated association in the lymphoblastoid cells. The association observed for chromosome 9 in both cell types appeared to be limited to the classical satellite III-type of heterochromatic, pericentromeric DNA. Using a single-copy probe along with the chromosome 17-specific pericentromeric probe, we determined that the association did not extend to the chromosome arms, but was limited to the pericentromeric region of chromosome 17. To accurately determine chromosome loss, we advocate the use of single-copy probes in addition to, or in place of, pericentromeric probes.

Adult↗

The European (European Dialysis and Transplantation Association-European Renal Association) Registry.

The European Dialysis and Transplantation Association-European Renal Association (EDTA-ERA) Registry, now some 30 years old, has collected data throughout Europe since its inception and now covers nearly 700 million people in some 36 countries. Approximately 2,000 centers report to it. It has been possible to follow the way in which treatment for renal failure has developed in Europe, and this has not always been uniform. The nature of the treatment offered, the survival of patients on treatment, and sequentially many areas of their management have been addressed and reported. The Registry continues to work both in the field of end-stage renal failure and other fields of renal disease. It is assisting in the development of national registries and subnational renal registries throughout Europe. The multinational, multicultural nature of its area of interests makes this Registry a uniquely placed source to study many aspects of the management of patients with renal disease and of contributing to their care in the variety of healthcare system that exist in Europe and in the countries bordering the Mediterranean.

Actuarial Analysis↗

The effects of oral droperidol versus oral metoclopramide versus both oral droperidol and metoclopramide on postoperative vomiting when used as a premedicant for strabismus surgery.

STUDY OBJECTIVE: To compare the efficacy of oral droperidol versus oral metoclopramide, or both oral droperidol and metoclopramide, on postoperative vomiting when used as a premedicant for strabismus surgery. DESIGN: Double-blind, randomized, prospective study. SETTING: Academic children's hospital. PATIENTS: 154 ASA physical status I and II ambulatory patients, ages 1 to 15 years, scheduled for strabismus surgery. INTERVENTIONS: Patients were randomly assigned to receive colored sugar water containing either droperidol 300 mcg/kg orally, metoclopramide 0.15 mg/kg orally, both droperidol 300 mcg/kg and metoclopramide 0.15 mg/kg orally, or no active ingredient (placebo group) as a premedicant. The premedications were given orally 1 to 1.5 hours prior to the operation. MEASUREMENTS AND MAIN RESULTS: Patients were analyzed for the number of episodes of vomiting from the time of their emergence from anesthesia through the first 24 hours postoperatively, including the convalescent period at home. Patients were also analyzed for length of hospital stay. There were no statistically significant differences between groups regarding age, premedication time, surgery time, or discharge time. Droperidol and droperidol-metoclopramide were significantly more effective (p < 0.012) than either the metoclopramide group or the placebo group in preventing postoperative nausea and vomiting following strabismus surgery. CONCLUSIONS: Our data suggest that oral droperidol 300 mcg/kg and the combination of oral droperidol 300 mcg/kg and metoclopramide 0.15 mg/kg are effective in reducing the frequency of vomiting within the first 24 hours after strabismus surgery. The combination of oral droperidol and oral metoclopramide is highly effective in reducing the frequency of vomiting postoperatively in strabismus ambulatory surgery patients (p = 0.017). This combination seems to represent an inexpensive alternative to the more costly ondansetron.

Administration, Oral↗

NG-methyl-L-arginine, an inhibitor of nitric oxide synthase, reverses interleukin-2-induced hypotension.

OBJECTIVE: To evaluate the role of NG-methyl-L-arginine as a modulator of the hyperdynamic shock induced by the administration of interleukin-2 (IL-2). DESIGN: A prospective, pilot clinical study. SETTING: Intensive care unit of a tertiary care center. PATIENTS: Three sequential patients with metastatic renal cell carcinoma who developed hypotension during their first course of treatment with high-dose IL-2 (18 x 10(6) IU/m2/day by continuous infusion for 5 days). INTERVENTIONS: Upon developing hypotension during their subsequent therapy with IL-2, patients were administered 12 mg/kg of NG-methyl-L-arginine. Thereafter, a dose of 4 mg/kg was given every 4 hrs, as needed, to maintain the systolic blood pressure above 100 mm Hg. MEASUREMENTS AND MAIN RESULTS: Invasive hemodynamic monitoring was instituted before the initiation of treatment with IL-2. Differences noted before, and 15 mins after, the administration of NG-methyl-L-arginine were analyzed using the paired t-test. NG-methyl-L-arginine (12 mg/kg) induced a significant antihypotensive effect (mean blood pressure increased from 87 +/- 4 to 121 +/- 7 mm Hg), accompanied by an increase of the systemic vascular resistance (549 +/- 51 to 860 +/- 167 dyne.sec/cm5) and pulmonary vascular resistance (81 +/- 16 to 117 +/- 29 dyne.sec/cm5). A decrease in the cardiac index was also documented (4.5 +/- 0.5 to 3.6 +/- 0.3 L/min/m2). No significant changes in pulmonary artery occlusion and central venous pressures were observed. Maintenance doses of 4 mg/kg of NG-methyl-L-arginine induced similar hemodynamic results, although the duration of the antihypotensive effect of NG-methyl-L-arginine decreased with sequential doses. CONCLUSIONS: The hemodynamic effects induced by IL-2 administration are reversed by NG-methyl-L-arginine, a nitric oxide synthesis inhibitor. These results provide evidence for the biological activity of NG-methyl-L-arginine when administered alone to hypotensive patients. While no adverse effects were observed in this preliminary study, issues of toxicity and effectiveness need to be defined further in formal clinical trials. NG-methyl-L-arginine may play a therapeutic role in the modulation of the extreme vasodilation induced by cytokine administration or in septic shock.

Adult↗

Plasma cholesterol and other cardiac risk factors in adolescent girls.

The aim was to examine the effects of smoking, physical activity, and body mass on total cholesterol and high density lipoprotein cholesterol (HDL-C) in adolescent schoolgirls in Sydney, Australia. Body mass index (BMI) and waist to hip ratio (WHR) were determined in 144 girls aged 15 to 18 years. Total cholesterol (TC) and HDL-C were estimated on fingerprick blood and behavioural variables assessed by questionnaire. Prevalence of overweight (> 90th centile for BMI) was less in Australian adolescents than reported from the USA. Smokers had lower total cholesterol than non-smokers; this was partly explained by a lower HDL-C in the smokers. Physical activity was associated with a less atherogenic TC/HDL-C ratio. Girls with BMI > 90th centile had higher mean TC/HDL-C and apoprotein B than the group as a whole but those > 90th centile for WHR did not.

Adolescent↗

Use of the multitrait multimethod (MTMM) to analyze family relational data.

In this article, the authors propose the logic of the multitrait multimethod (MTMM) approach for analysis of data as an alternative solution for examining family relational data. Application of the MTMM logic permits the assessment of common perspectives shared by all family members and of the unique perspectives of individuals. The advantages of using this approach in family research include the ability to (a) maintain consistency between systems theory views of family-as-a-unit, and (b) delineate patterns of agreement, disagreement, or both among family members.

Adult↗

Immunomodulating effects of synchronised plasmapheresis and intravenous bolus cyclophosphamide in systemic lupus erythematosus.

Recent studies have suggested that synchronised plasmapheresis and intravenous pulse cyclophosphamide therapy reduce disease activity in SLE patients. The aim of the present study was to examine the immunomodulating effects of this therapy and compare it with changes seen with cyclophosphamide alone. Four patients with active SLE were studied. Two were treated with synchronised therapy and two received cyclophosphamide only for up to 26 weeks. Disease activity was measured by the SLE disease activity index (SLEDAI). Immunological studies were performed immediately prior to each treatment. Patients in both treatment groups improved as reflected by a fall in mean SLEDAI scores: synchronised therapy 33.5 to 11; cyclophosphamide only 13.5 to 4.5. Following synchonised therapy only there was a prompt and sustained increase in the mean percentage of CD8+ cells (20.8 to 54.8) which resulted in a fall in the CD4:CD8 ratio (1.95 to 0.62). With both treatment modalities there was a fall in the proportion of CD20+ cells (B lymphocytes) (synchronised therapy 10.5 to 3.2; cyclophosphamide only 5.6 to 2.2). However, only synchronised therapy resulted in a fall in the in vitro production of immunoglobulins which was unchanged or increased following cyclophosphamide alone. These results suggest that although both treatment modalities are efficacious in the treatment of active SLE they produce different immunomodulatory effects. Thus, both therapies reduce the number of circulating B lymphocytes whereas synchronised therapy also modifies cellular immunity by promoting the emergence of a phenotypic suppressor T lymphocyte population.

Adjuvants, Immunologic↗

[Mutagenicity studies of iodixanol, a new non-ionic isotonic contrast medium].

A new non-ionic isotonic contrast medium, iodixanol (a diastereomeric mixture of 5,5'-[(2-hydroxytrimethylene) bis (acetylimino)] bis [N, N'-bis (2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzene-dicarboxamide]) was studied for mutagenicity by using the Ames method, in vitro cytogenetics and micronucleus test. Iodixanol had no mutagenic effect on S. typhimurium (TA1535, TA1537, TA1538, TA98 and TA100) or E. coli (WP2uvrA) in the reverse mutation assay with or without metabolic activations. In the cytogenetic study, iodixanol had no effect on the Chinese hamster cells with or without metabolic activations. Intravenous injections of iodixanol for two times at a dose of 800, 1,600 or 3,200 mgI/kg in the mouse micronucleus test did not increase the incidence of micronucleated polychromatic erythrocytes. These results show that iodixanol has no mutagenic potential.

Animals↗

Antiphospholipid antibodies in a healthy population: methods for estimating the distribution.

OBJECTIVE: To determine the distribution of antibodies to cardiolipin (IgG, IgM and IgA) in a healthy population. To classify subjects according to a cutpoint in order to determine what level of antibody measurement would yield 95% specificity. METHODS: Antiphospholipid (aPL) antibodies were measured using a conventional ELISA technique, with isotype specific antibody, to determine levels of IgG, IgM and IgA binding to cardiolipin. The subjects were 282 Red Cross blood donors, 82 undergraduate medical and nursing students, and 13 laboratory volunteers. RESULTS: The distribution of aPL antibodies measured in units of optical density is significantly skewed, while the distribution of aPL antibodies measured on the log scale is nearly symmetric. Neither distribution is normally distributed. There was no evidence that aPL antibodies differed significantly by age (up to age 50) or sex. We estimate the 90th, 95th, and 99th percentiles for IgG, IgM and IgA antibodies for the optical densities and binding indices. CONCLUSION: For 95% specificity we conclude that an adjusted IgG optical density above 0.386, an adjusted IgM optical density above 0.301, or an adjusted IgA optical density above 0.085 be considered positive.

Adult↗

Strategies to promote preterm breastfeeding.

A breastfeeding support programme based on the principles of normal lactation has been adapted to meet the needs of women and their premature or sick infants. The four specific areas are: the initiation and maintenance of lactation in-hospital breastfeeding growth and development transfer management. This approach has indicated substantial physiological and psychological benefits for mothers, and clear possibilities of maximising preterm infant growth.

Breast Feeding↗

The effect of Norplant on glucose metabolism under hyperglycemic hyperinsulinemic conditions.

OBJECTIVES: To assess the impact of a levonorgestrel-releasing implant contraceptive (Norplant; Wyeth-Ayerst Laboratories, Philadelphia, PA) on glucose metabolism. DESIGN: Prospective evaluation of insulin action and secretion in women under hyperglycemic hyperinsulinemic clamp conditions in the midfollicular phase before and 8 weeks after Norplant placement. SETTING: Yale University Clinical Research Center. PARTICIPANTS: Seven previously normally cycling, nonobese, nondiabetic women participated in the study. INTERVENTIONS: Norplant insertion. MAIN OUTCOME MEASURES: Basal levels of glucose and insulin, as well as glucose-mediated insulin secretion, glucose uptake, and tissue sensitivity to insulin were assessed using the hyperglycemic hyperinsulinemic clamp technique before and after Norplant insertion. RESULTS: Norplant placement did not alter the fasting glucose or insulin levels. However, it was associated with a significant 37% increase in the first phase insulin response from a control level of 51 +/- 8 to 70 +/- 10 microU/mL (conversion factor to SI unit, 7.175), and a significant 48% increase in the second phase insulin response from 60 +/- 5 to 89 +/- 8 microU/mL. In association with this increase in insulin levels after Norplant insertion, total mean body glucose uptake (M) increased from 8.08 +/- 0.91 to 9.53 +/- 0.95 mg/kg per minute. However, when expressed as the total body glucose uptake per unit of insulin, the M:I ratio (a measure of tissue sensitivity to insulin) decreased significantly from a mean of 0.12 +/- 0.02 to 0.10 +/- 0.01 mg/kg per minute per microU/mL. CONCLUSION: Although Norplant insertion does not alter basal glucose and insulin levels, tissue sensitivity to insulin under hyperglycemic hyperinsulinemic conditions is decreased after Norplant insertion.

Adult↗

Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27.

An IL-1-stimulated protein kinase cascade resulting in phosphorylation of the small heat shock protein hsp27 has been identified in KB cells. It is distinct from the p42 MAP kinase cascade. An upstream activator kinase phosphorylated a 40 kDa kinase (p40) upon threonine and tyrosine residues, which in turn phosphorylated a 50 kDa kinase (p50) upon threonine (and some serine) residues. p50 phosphorylated hsp27 upon serine. p40 and p50 were purified to near homogeneity. All three components were inactivated by protein phosphatase 2A, and p40 was inactivated by protein tyrosine phosphatase 1B. The substrate specificity of p40 differed from that of p42 and p54 MAP kinases. The upstream activator was not a MAP kinase kinase. p50 resembled MAPKAPK-2 and may be identical.

Amino Acid Sequence↗

Duplication and deletion of chromosome band 2(p21p22) resulting from a familial interstitial insertion (2;11)(p21;p15).

Routine amniocentesis for advanced maternal age led to the prenatal diagnosis of a fetus with a karyotype of a 46,XX,del(2)(p21p22). At delivery the baby had holoprosencephaly as the major clinical finding, which has been associated with a deletion of band 2p21 in several other case reports. Chromosome studies of the parents showed a normal 46,XY karyotype in the father, and a balanced interstitial insertion 46,XX dir ins (11;2)(p15.1;p21p22) in the mother. Subsequent chromosome studies of other relatives documented a 23-year-old half-brother of the proposita with a partial trisomy for the segment deleted in the proposita. The half-brother showed the derivative chromosome 11 from the mother, resulting in a 46,XY,der(11)dup(2)(p21p22) karyotype. Major clinical findings include short stature, mild developmental delay, and behavior abnormalities. A half-sister of the proposita is also a balanced carrier of the dir ins (11;2) (p15.1;p21p22.2). The association of the deletion chromosome band 2p21 and the clinical finding of holoprosencephaly is further supported by the findings in this family.

Adult↗

Aneusomy of chromosomes 7 and 17 detected by FISH in prostate cancer and the effects of selection in vitro.

Twenty prostate tumor specimens, obtained from radical prostatectomies, and two lymph node metastases were examined by classical and molecular cytogenetic methods. A sample from each tumor was analyzed histologically and used for touch preparations. Adjacent samples were used for preparation of single-cell suspensions before cell culture (DirFISH) and for establishing cell cultures, which were subsequently harvested for classical G-banding analysis. Fluorescence in situ hybridization (FISH) was performed on touch preparations, DirFISH, and cells obtained from tissue culture. Biotinylated pericentromeric probes for chromosomes 7 and 17, in addition to a digoxigenin-labeled X-chromosome probe, were used in a dual-color FISH assay. The results indicated that, in uncultured tumor cells, chromosome 17 was lost in 55% of specimens, chromosome 7 was gained in 16% of specimens, and 9% of specimens showed large tetraploid populations. After cell culture, 23% of specimens showed loss of chromosome 17, no specimens showed gain of chromosome 7, and no tetraploid populations were present. This study suggests that loss of chromosome 17 may play an important role in the development of prostate cancer, and that genetic changes observed after selection in vitro may not represent those in the original tumor.

Aneuploidy↗

Phase II trial of low dose gamma-interferon in metastatic renal cell carcinoma.

We conducted a phase II trial to confirm the activity of fixed, low dose gamma-interferon in metastatic renal cell carcinoma. A total of 35 patients with metastatic renal cell carcinoma, who had not received prior immunotherapy and who had a Zubrod performance status of 2 or less, was enrolled in this study. Primary tumors were controlled by nephrectomy or embolization before treatment began. gamma-Interferon was administered weekly as a subcutaneous injection at a fixed dose of 100 micrograms. Toxic effects were limited to low grade fever, chills and myalgias within 24 hours of injection. There were no incidences of grade 3 or 4 toxicity. Responses could be evaluated in 34 patients. There were 1 complete and 4 partial responses, for an objective response rate of 15% (95% confidence interval 5 to 32%). Durations of response to date are 21+, 17+, 13+, 9 and 2 months. We conclude that gamma-interferon is an active agent for metastatic renal cell carcinoma when administered according to this dose and schedule. The response rate compares favorably with those of alpha-interferon and interleukin-2, and toxicity is minimal. gamma-Interferon has excellent potential for use in combination with other biological or chemotherapeutic agents and in the adjuvant setting.

Adult↗