Search PubMed⌕ Search

Biomedical subjects

J Jones

Publications and source records attributed to J Jones.

At least 451 records · Page 25Linked to original sources

Transactivation of Ds elements in plants of lettuce (Lactuca sativa).

The maize transposable element, Activator (Ac), is being used to develop a transposon mutagenesis system in lettuce, Lactuca sativa. In this paper, we describe somatic and germinal transactivation of Ds by chimeric transposase genes in whole plants. Constructs containing either the Ds element or the Ac transposase open reading frame (ORF) were introduced into lettue. The Ds element was located between either the 35S or the Nos promoter and a chimeric spectinomycin resistance gene (which included a transit peptide), preventing expression of spectinomycin resistance. The genomic coding region of the Ac transposase was expressed from the 35S promoter. Crosses were made between 104 independent R1 plants containing Ds and three independent R1 plants expressing transposase. The excision of Ds in F1 progenies was monitored using a phenotypic assay on spectinomycin-containing medium. Green sectors in one-third of the F1 families indicated transactivation of Ds by the transposase at different developmental stages and at different frequencies in lettuce plants. Excision was confirmed using PCR and by Southern analysis. The lack of green sectors in the majority of F1 families suggest that the majority of T-DNA insertion sites are not conducive to excision. In subsequent experiments, the F1 plants containing both Ds and the transposase were grown to maturity and the F2 seeds screened on medium containing spectinomycin. Somatic excision was again observed in several F2 progeny; however, evidence for germinal excision was observed in only one F2 family.

Base Sequence↗

The effects of recombinant insulin-like growth factor I administration on growth hormone levels and insulin requirements in adolescents with type 1 (insulin-dependent) diabetes mellitus.

Type 1 (insulin-dependent) diabetes mellitus in adolescence is associated with reduced levels of insulin-like growth factor I, elevated growth hormone concentrations and insulin resistance. In order to determine whether restoring insulin-like growth factor I levels to normal might lead to a reduction in growth hormone levels and insulin requirements, we undertook a double-blind placebo controlled study of a single s.c. dose of recombinant insulin-like growth factor I (40 micrograms/kg body weight) in nine late pubertal subjects with Type 1 diabetes. After administration of placebo or insulin-like growth factor I at 18.00 hours, a variable rate insulin infusion was used to maintain euglycaemia overnight. Plasma insulin-like growth factor I, growth hormone, free insulin, and intermediate metabolite concentrations were monitored throughout the study. Recombinant insulin-like growth factor I led to a rise in plasma concentrations which reached a peak at 5.5 h (413.1 +/- 28.2 ng/ml, mean +/- SEM). Mean growth hormone levels between 20.00 and 08.00 hours were significantly reduced after recombinant insulin-like growth factor I (19.4 +/- 4.0 compared with 33.6 +/- 5.8 mU/l; p = 0.01), as were the insulin requirements for euglycaemia (0.25 +/- 0.02 compared with 0.31 +/- 0.04 mU.kg-1.min-1; p = 0.03). Plasma free insulin levels were lower after recombinant insulin-like growth factor I administration (31.9 +/- 2.7 compared with 67.9 +/- 16.0 mU/l; p = 0.001) but no significant differences in ketone or lactate levels were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A large outbreak of gastroenteritis caused by diarrheal toxin-producing Bacillus cereus.

An outbreak of diarrhea occurred after a university field day. Of 643 attendees who returned mailed questionnaires, 139 (22%) reported illness. Persons who ate barbecued pork, which was unrefrigerated for 18 h after cooking, were five times more likely to become ill than those who did not eat pork (26% vs. 5%; relative risk, 5.4; 95% confidence interval, 1.4-20.9). A leftover pork sample grew a Bacillus cereus isolate, > 10(5) cfu/g, that produced diarrheal toxin. Thirty-four percent of ill persons noted onset of illness outside the 6- to 24-h incubation period traditionally ascribed to B. cereus-mediated diarrhea, and an unusually high percentage (23%) noted fever. B. cereus may cause a wider spectrum of disease than previously described.

Bacillus cereus↗

Role of T-cell tolerance in the persistence of hepatitis B virus infection.

Infants born to hepatitis B e antigen (HBeAg)-positive hepatitis B virus (HBV) carrier mothers invariably become persistently infected. To investigate the role of immunologic tolerance mechanisms in chronic infection of the newborn, we have generated HBeAg-expressing transgenic mice (B10.S-Tg31e). These mice were tolerant to both HBeAg and the nonsecreted HBcAg at the T-cell level. Furthermore, nontransgenic littermates born to HBeAg-expressing mothers showed lowered T-cell responses to HBc/HBe antigens, suggesting that tolerogenic HBeAg may cross the placenta. Tg mice did not produce antibody to HBeAg but did produce immunoglobulin M (IgM) antibodies to HBcAg via a T cell-independent pathway. The coexistence of tolerance to HBc/HBe T-cell determinants and production of antibody to HBcAg in vivo parallels the immunologic status of neonates born to carrier mothers. These observations suggest that expression of HBeAg may represent a viral strategy to guarantee persistence after perinatal infection. Further studies in F1 hybrid Tg mice (B10 x B10.S-Tg31e) illustrated that "self" tolerance to HBeAg is variable, depending on the major histocompatibility complex (MHC) genotype. A proportion of T cells recognizing e129-140 in the context of I-Ab evade induction of tolerance, persist in the periphery, and can be activated in vivo by a single injection of the 12 residue T-cell self-peptide. Furthermore, the self-reactive T cells can cooperate with self-reactive, HBeAg-specific B cells to mediate in vivo production of autoantibody sufficient to neutralize detection of the autoantigen in serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Outbreak of gastroenteritis due to Salmonella enteritidis from locally produced grade A eggs, South Carolina.

Recent investigations of outbreaks of Salmonella enteritidis gastroenteritis among humans, especially in the northeastern United States, implicate grade A shell chicken eggs as the likely vehicle of transmission. In April 1991 we investigated an outbreak of S enteritidis infections after a wedding anniversary celebration in Beaufort, South Carolina. Sixty-eight percent of persons who ate a macaroni and cheese dish, but none of the 16 attendees who did not, became ill (P < .001). The chef used six grade A eggs in the macaroni and cheese and may have undercooked it. The egg supplier processed eggs exclusively from farms in South Carolina and North Carolina. This outbreak suggests that the epidemic of S enteritidis in flocks of laying hens the consequent threat of human infection has spread to the Carolinas.

Disease Outbreaks↗

Mechanical efficiency of children with spastic cerebral palsy.

In this feasibility study, the authors compared the mechanical efficiency of nine children with spastic diplegia with that of nine able-bodied children, matched for gender. They also compared resting energy expenditure in the two groups. The children with CP had significant reductions in mechanical efficiency at maximum stable work-load and marginally significant reductions when they were compared at 200 kg-m/min work-load. The efficiency of able-bodied children at 200 kg-m/min was unexpectedly reduced. There were no differences in resting energy expenditure. Mechanical efficiency may be a useful objective technique to assess the effects of interventions intended to improve the efficiency of the movement of children with CP.

Biomechanical Phenomena↗

Odontogenic squamous cell carcinoma with osseous metaplasia.

Intra-osseous carcinomas of the jaw are rare tumours, thought to arise from residual elements of the odontogenic epithelium. We report an additional case which, unusually, was characterised by marked osseous metaplasia. We propose that the new bone formed around the tumour is the result of an epithelial-mesenchymal interaction between malignant odontogenic epithelium and osteogenic precursor cells in the surrounding stroma.

Carcinoma, Squamous Cell↗

X linked exudative vitreoretinopathy: clinical features and genetic linkage analysis.

A four generation family in which familial exudative vitreoretinopathy is inherited as an X linked condition is described. Essentially the condition is one of abnormal vascularisation and signs at birth are those of a retinopathy superficially resembling retinopathy of prematurity, retinal folds, or, in advanced cases, enophthalmos or even phthisis. Prognosis depends on the progression of the retinal changes. The family members, including seven affected males and five obligate carrier females, have been types for 20 DNA markers, and linkage analysis suggests a gene locus either at Xq21.3 or at Xp11. As the latter region includes the locus for the gene for Norrie disease, it is possible that this and X linked vitreoretinopathy are allelic. We can further speculate that the differences in severity of the clinical manifestations are dependent only upon the timing of the insult.

Adolescent↗

Measuring hospital workload in general medicine.

The study described here used routine data sources to consider three aspects of hospital workload-volume and case-mix of inpatients; volume of outpatients; and volume of procedures.

Age Distribution↗

The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03.

PURPOSE: This study was designed to evaluate the efficacy of leucovorin-modulated fluorouracil (5-FU) as adjuvant therapy for patients with Dukes' stage B and C colon cancer. PATIENTS AND METHODS: Data are presented from 1,081 patients with Dukes' stage B and C carcinoma of the colon entered into National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol C-03 between August 1987 and April 1989. Patients were randomly assigned to receive either lomustine (MeCCNU), vincristine, and 5-FU (MOF), or leucovorin-modulated 5-FU (LV + 5-FU). The mean time on study was 47.6 months. RESULTS: Comparison between the two groups indicates a disease-free survival advantage for patients treated with LV + 5-FU (P = .0004). The 3-year disease-free survival rate for patients in this group was 73% (95% confidence interval, 69% to 77%), compared with 64% (95% confidence interval, 60% to 68%) for patients receiving MOF. The corresponding percentage of patients surviving was 84% for those randomized to receive LV + 5-FU and 77% for the MOF-treated cohort (P = .003). At 3 years of follow-up, patients treated with postoperative LV + 5-FU had a 30% reduction in the risk of developing a treatment failure and a 32% reduction in mortality risk compared with similar patients treated with MOF. CONCLUSION: Treatment with LV + 5-FU significantly prolongs disease-free survival and results in a significant benefit relative to overall survival. These findings, when considered together with results from a recent meta-analysis demonstrating a benefit from LV + 5-FU in advanced disease, provide evidence to support the concept of metabolic modulation of 5-FU.

Chemotherapy, Adjuvant↗

Treatment of familial male precocious puberty with spironolactone, testolactone, and deslorelin.

Combined antiandrogen (spironolactone) and aromatase inhibitor (testolactone) are effective for the short term treatment of familial male precocious puberty. During this therapy, plasma testosterone levels remain in the adult range, since spironolactone blocks the testosterone receptor without significantly affecting plasma testosterone levels. After our initial 18-month pilot study, we continued to treat eight boys with the combined therapy for 2.0-4.2 yr. During this time all boys exhibited a pubertal rise in gonadotropin secretion and a diminishing response to treatment, which was manifested by the recurrence of clinical features of puberty and an increase in the bone maturation rate (P < 0.05). Addition of the LHRH agonist deslorelin (4 micrograms/kg.day, sc) to the combined therapy decreased peak LH, plasma testosterone, bone maturation rate, and growth velocity (P < 0.05) over the next year. We conclude that the rise in gonadotropin levels during central activation of hypothalamic LHRH secretion in boys with familial male precocious puberty causes a partial escape from the combined effect of spironolactone and testolactone. The addition of deslorelin to the combined therapy appears to restore the control of puberty in this setting.

Age Determination by Skeleton↗

Long-term testolactone therapy for precocious puberty in girls with the McCune-Albright syndrome.

We used the aromatase inhibitor testolactone (40 mg/kg.day) to treat 12 girls with precocious puberty due to the McCune-Albright syndrome for periods of 0.5-5 yr. In the 7 girls who received testolactone for at least 3 yr, the mean +/- SD serum estradiol level was 618 +/- 268 pmol/L at the start of therapy and fell to 156 +/- 84 pmol/L at 1 yr, 116 +/- 48 pmol/L at 2 yr, and 241 +/- 260 pmol/L at 3 yr (P < 0.05 compared to the start of therapy), with recurrent ovarian cysts at 3 yr in 2 patients. These 7 girls averaged 8 menses/yr before therapy. The average frequency of menses decreased to 2 episodes/yr during the first year of treatment, 3/yr during the second year, and 4/yr during the third year. The mean +/- SD testosterone levels were slightly above the normal prepubertal range (0.51 +/- 0.2 nmol/L) before treatment and did not change significantly during treatment. The mean +/- SD androstenedione levels rose from 1.1 +/- 0.6 nmol/L before treatment to 2.1 +/- 0.1 nmol/L at 2 yr and 2.8 +/- 0.1 nmol/L after 3 yr of treatment (P < 0.05 compared to before treatment) and were consistent with normal adrenarche. The mean predicted adult stature was 143.0 +/- 7.8 cm before treatment and 147.3 +/- 11.5 cm at 3 yr (P = NS). In 3 of 12 girls, all with bone age greater than 12 yr, the gonadotropin responses to LHRH indicated early central precocious puberty after 1-4 yr of treatment. The adverse effects of testolactone were transient abdominal pain, headache, and diarrhea in 3 girls and elevated hepatic enzymes in 1 girl who had abnormal liver function before treatment. Six families acknowledged difficulty in adhering to the daily dosing schedule. We conclude that testolactone can be effective in the treatment of LHRH-independent precocious puberty in girls with McCune-Albright syndrome, but that some patients exhibit an escape from the effects of treatment after 1-3 yr.

Age Determination by Skeleton↗

The effects of dexamethasone treatment on immunoreactive and bioactive insulin-like growth factors (IGFs) and IGF-binding proteins in normal male volunteers.

Glucocorticoids inhibit somatic growth in man and laboratory animals, and have long been regarded as suppressors of both stimulated GH secretion and insulin-like growth factor (IGF) activity. Recent evidence suggests, however, that glucocorticoids can be potent GH secretagogues in their own right with concomitant increases in circulating IGF-I levels. IGFs circulate tightly bound to a group of high-affinity binding proteins (IGFBPs) which modulate their actions. In order to investigate the effects of glucocorticoids on serum levels of IGFs and IGFBPs, normal male volunteers were sampled over 24-h periods before and directly after treatment with dexamethasone (2 mg twice daily) for 96 h. Following dexamethasone administration, all volunteers showed a marked increase in mean +/- S.E.M. IGF-I levels over the 24-h sampling period (292.2 +/- 31.8 before dexamethasone, 425.9 +/- 37 micrograms/l after dexamethasone, P < 0.005); there was no change in mean IGF-II levels. Integrated mean insulin levels were raised by dexamethasone treatment (50 +/- 4.6 before dexamethasone, 117 +/- 13.4 mU/l after dexamethasone, P = 0.002) and IGFBP-1 was significantly suppressed (42.9 +/- 8.2 before dexamethasone, 28.0 +/- 7.9 micrograms/l after dexamethasone, P < 0.001). IGFBP-2 levels were similarly suppressed after dexamethasone (319.5 +/- 24.5 before dexamethasone, 214.8 +/- 8.5 micrograms/l after dexamethasone, P = 0.002), and there was a significant increase in IGFBP-3 levels from 3.24 +/- 0.25 to 3.67 +/- 0.32 mg/l (P = 0.0153). Mean IGF bioactivity over the sampling period after dexamethasone was reduced by approximately 60% (0.93 +/- 0.39 before dexamethasone, 0.39 +/- 0.05 U/ml after dexamethasone, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationship between follicular fluid levels of insulin-like growth factor binding protein-1 and sex steroids from normal human ovarian follicles.

The aim of this study was to examine the possible correlations between follicular fluid insulin-like growth factor binding protein 1 (IGFBP-1) and follicular fluid and serum parameters of granulosa cell function. Twenty-six subjects undergoing diagnostic laparoscopy for infertility had follicular fluid samples collected. Subjects were aged 20-42 years, were having regular ovulatory cycles and either had tubal disease or a partner with male factor infertility. Sex steroids, insulin-like growth factor 1 (IGF-1) and IGFBP-1 were measured by radioimmunoassay. Follicular fluid levels of IGFBP-1 were significantly correlated with levels of estradiol, progesterone in follicular fluid and with serum IGFBP-1 levels, and negatively correlated with follicular fluid androstenedione levels. These results suggests that IGFBP-1 may have a role in the regulation of human ovarian follicles.

Adult↗