Search PubMed⌕ Search

Biomedical subjects

J A Roberts

Publications and source records attributed to J A Roberts.

At least 73 records · Page 4Linked to original sources
PubMed1999

Regulation of cyclic AMP by extracellular ATP in cultured brain capillary endothelial cells.

1 In primary unpassaged rat brain capillary endothelial cell cultures (RBECs), using reverse-transcriptase PCR with primers specific for P2Y receptor subtypes, we detected mRNA for P2Y2, P2Y4 and P2Y6, but not P2Y1 receptors. 2 None of the various nucleotides tested reduced forskolin elevated cyclic AMP levels in RBECs. ATP and ATPgammaS, as well as adenosine, enhanced cyclic AMP accumulation in the presence of forskolin. 3 Comparison of the concentration response curves to ATPgammaS with those for ATP and adenosine, at different incubation times, indicated that the response to purine nucleotides was not wholly dependent on conversion to adenosine. Adenosine deaminase abolished the response to adenosine but only reduced the response to ATP by about 50%. These results suggest the participation of a receptor responsive to nucleotides. 4 Isobutylmethylxanthine and 8-sulphophenyltheophylline prevented the cyclic AMP response, while neither 8-cyclopentyl-1, 3-dipropylxanthine nor SCH58261 were effective antagonists. 2-chloradenosine gave a robust response, but neither 2-chloro-N6-cyclopentyladenosine nor CGS 21680 were agonists. 5 These results show that adenosine and ATP can elevate the cyclic AMP levels of brain endothelial cells by acting on receptors which have a pharmacology apparently distinct from known P2Y and adenosine receptors.

Adenosine↗
PubMed1999

The economic aspects of hepatitis C-- implications for haemophilia.

This paper considers the literature relating to the course of hepatitis C infection and its implications for those with haemophilia. It goes on to discuss a model that assessed the economic aspects of treating hepatitis C cases with interferon-alpha, discusses recent changes in recommended treatment of hepatitis C and critically reviews the model and its application to patients with haemophilia.

Adult↗
PubMed1999

Bladder infection in the menopausal monkey.

PURPOSE: The highest incidence of urinary tract infection in females occurs in elderly women. This study was done to determine whether this is due to the declining immune response that occurs during advancing age, or the menopausal state in the aged. MATERIALS AND METHODS: Adult female monkeys (average age 19 years) were studied, half being subjected to bilateral oophorectomy to produce the menopause. In addition, old females (average age 29 years) already at menopause were studied before and after hormonal replacement with estradiol and progesterone. Bacterial adherence to vaginal cells was studied prior to and after urethral infection with E. coli. Plasma estradiol and progesterone levels were done, as well as white blood counts, plasma cytokine assays and serum antibody titers. RESULTS: Bacteriuria was not prolonged, nor was there a significant difference in bacterial adherence to vaginal cells due to menopause. Interleukin-1 levels were depressed after surgical menopause but not as much as found in the old menopausal females and this low level was not corrected by hormonal replacement. The initial interleukin-2 levels were higher after spontaneous menopause, but the increasing plasma levels seen in cycling animals after infection did not occur in the aged menopausal females following infection even after hormone replacement. The antibody titers to the E. coli infection showed a trend to a lessened response to infection after menopause but were not significantly decreased. CONCLUSIONS: The deficient Il-1, Il-2 and antibody response following infection was not corrected by hormone replacement and thus appears to be due to aging rather than lack of female hormones. These facts may be explained by the T cell senescence known to occur in aged individuals.

Age Factors↗
PubMed1999

Bromodeoxyuridine alternating with radiation for advanced uterine cervix cancer: a phase I and drug incorporation study.

PURPOSE: Preclinical studies show a significant increase in the ratio of the radiosensitizer bromodeoxyuridine (BUdR) in tumors versus the intestinal mucosa during the drug elimination period, compared with the ratio during drug infusion. We constructed a phase I study in patients with locally advanced cervix cancer, using alternating cycles of BUdR and radiation therapy (RT). PATIENTS AND METHODS: Eighteen patients with stage IIB to IVA cervix cancer participated. A treatment cycle consisted of a 4-day BUdR infusion followed by a week of pelvic RT, 15 Gy twice daily in 1.5-Gy fractions. After three cycles, additional BUdR was infused, followed by brachytherapy. The fraction of thymidine replaced by BUdR and the fraction of cells incorporating BUdR were determined in rectal mucosa and tumor biopsies at the end of the first BUdR infusion (day 5), at the middle of the first RT week (day 10), and at the time of brachytherapy. RESULTS: Dose-limiting toxicity was observed in one of 16 patients receiving 1,000 mg/m2/d x 4 days and in both patients receiving 1,333 mg/m2/d x 4 days each cycle. After a median follow-up of 39 months, 12 patients (66%) were free of pelvic disease and nine (50%) were alive and disease free. The ratio of tumor to rectum BUdR incorporation averaged 1.5 to 1.8 and did not differ significantly between day 5 and day 10. A trend toward reduced ratio was observed at brachytherapy. Drug-containing cells in rectal biopsies migrated from the crypts to the mucosal surface. CONCLUSION: In this schedule, 1,000 mg/m2/d is the maximum-tolerated dose of BUdR. BUdR incorporation levels in tumors were consistent with clinically significant radiosensitization. The migration of BUdR-containing rectal mucosa cells from the crypts to the surface at the time of RT suggests that this regimen may offer a relative sparing of the mucosa from radiosensitization.

Adenocarcinoma↗
PubMed1999

Training and generalization of sexual abuse prevention skills for women with mental retardation.

Previous research has shown that behavioral skills training to teach sexual abuse prevention skills to women with mental retardation results in skill acquisition but poor generalization. In this investigation we evaluated procedures for enhancing generalization following training. Five women with mental retardation received 10 behavioral skills training sessions followed by in situ training when the skills did not fully generalize. Behavioral skills training resulted in skill acquisition and in situ training produced generalized responding during naturalistic assessments.

Adult↗
PubMed1999

A study of infectious intestinal disease in England: plan and methods of data collection.

The Committee on the Microbiological Safety of Food, set up in 1989 by the Department of Health in response to national epidemics of foodborne infection, considered the available evidence and commissioned a study of infectious intestinal disease (IID) in England. Seventy practices (with 489,500) patients overall) recruited from the Medical Research Council's General Practice Research Framework between August 1993 and January 1995 collected data for one year. The practice populations were representative of practices in England by area and urban/rural location, but with fewer small and affluent practices. There were five main components. i) A population cohort of 9776 (40% of those eligible) were enrolled to estimate the incidence and aetiology of IID in the community, and a large proportion were followed up. A median of 10% of patients on practice age-sex registers had moved away or died. ii) A nested case control component based on cases ascertained in the cohort was used to identify risk factors for IID in the community. iii) In a case control component used to identify risk factors and to estimate the incidence and aetiology of IID presenting in 34 general practices 70% of the 4026 cases returned risk factor questionnaires, 75% submitted stools, and matched controls were found for 75% of cases. iv) An enumeration component was used to estimate the incidence of IID presenting to general practitioners (GPs) in 36 practices and the proportion of specimens sent routinely for microbiological examination. v) In a socioeconomic costs component used to estimate the burden of illness of IID in the community and presenting to GPs 63% of those who returned a risk factor questionnaire also returned a socioeconomic questionnaire and were representative by age, sex, and social class. Despite variable enrolment and compliance the study sample had sufficient power for the multivariable analysis. The characteristics associated with low enrollment and compliance must be considered in the interpretation of the main study results.

Case-Control Studies↗
PubMed1999

Expression of p53 in epithelial carcinoma of the ovary after chemotherapy.

OBJECTIVE: To compare the expression of p53 protein before and after chemotherapy in epithelial carcinoma of the ovary. STUDY DESIGN: Thirty patients were identified during a 10-year period with both their primary surgery and laparotomy after chemotherapy at the same institution. Tissue was processed from paraffin blocks, exposed to an antihuman p53 monoclonal antibody, then stained. Patient records were reviewed for survival data. RESULTS: Twelve of 30 (40%) patients' tissue initially stained positive for p53. Seventeen of 30 (56.7%) were negative, and one (3.3%) was mixed. Eight of 12 (66.7%) initially positive remained so after chemotherapy, 2 converted to negative, and 2 converted to mixed expression. One patient with mixed expression converted to positive after chemotherapy. Seventeen tissues initially negative remained unchanged. CONCLUSION: Chemotherapy did not permanently alter the expression of p53 detected by immunohistochemical staining in the majority (83.3%) of patients with epithelial ovarian cancer; 16.7% (all initially over-expressing p53) did show some decrease. This may have been due to deactivation of the mutated p53 gene, spontaneous mutation, selective growth within a heterogeneous population or alteration of p53 protein.

Adult↗
PubMed1998

Customized gynecologic interstitial implants: CT-based planning, dose evaluation, and optimization aided by laparotomy.

PURPOSE: Interstitial perineal implants may be utilized to deliver a high local radiation dose in the treatment of advanced gynecologic malignancies. Lack of knowledge of the precise anatomic relationships between the implant and the target and critical organs may limit efficacy and increase complication risks. Computed tomography (CT)-based planning, dose evaluation, and optimization of customized interstitial implants, aided by laparotomy, have been developed to overcome these limitations. METHODS AND MATERIALS: Twenty patients with locally advanced gynecologic malignancies treated between May 1990 to October 1996 with external irradiation and one or two implants. Interstitial implants were performed when intracavitary brachytherapy was judged to be inadequate or when the response to external radiation and an intracavitary implant was not satisfactory. Customized interstitial implants were planned using preimplantation CT to determine catheter angles and paths that best implanted the target while avoiding pelvic bones and organs. Laparotomy aimed at lysing bowel adhesions, placement of omental carpet, and refining needle placement. Postimplantation CT was used for loading optimization and dose evaluation. RESULTS: Catheter angles 15-25 degrees were found to adequately implant anteriorly laying targets while avoiding pubic bones and bladder. Adhesiolysis of bowel loops from the vaginal apex was required in patients with prior hysterectomy. Small modifications in catheter placements were made during laparotomy in all implants. Postimplantation CTs showed deviations of the catheter positions compared with the planning CTs and were essential in determining target and organ doses and loading optimization. At a median follow-up of 42 months (range: 9-80 months), local control rate is 55% and disease-free survival 40%. Late complications occurred in 2 of 11 of patients without local recurrence. CONCLUSIONS: CT-based planning, loading optimization, and dose evaluation of customized implants improve radiation dose delivery. Laparotomy enhances implant accuracy and safety. Local tumor control rate is still unsatisfactory. It reflects the shortcomings of technical advances alone in poor prognosis tumors like those selected for this series.

Adenocarcinoma↗
PubMed1998

Effect of age and hormonal state on cytokine synthesis in the monkey.

The authors studied plasma cytokine activity using cross reactive polyclonal antibodies to human cytokines in young and old female monkeys to determine if age had any effect on cytokine secretion, and compared hormonal effects as well. While interleukin 1 (IL-1) was not higher in aged cycling monkeys, it was after menopause. Menopause depressed IL-2 activity also. Variable results were seen with the other cytokines.

Aging↗
PubMed1998

Rapidly progressive osteoarthrosis of the hip.

Rapidly progressive cases of primary idiopathic hip osteoarthrosis are well known and recognized. Their prevalence and significance are, however, often poorly appreciated. This article aims to assess the prevalence of the condition in a United Kingdom district general hospital. Several points arise: 1) Patients suffering rapid deterioration do not always alert their surgeon to the worsening symptoms; 2) Waiting lists need regular administration and the patients regular review while on such lists; 3) Decisions about surgery and case selection should be made purely on clinical grounds with financial, political, and administrative considerations accorded little or no relevance.

Adult↗
PubMed1998

Molecular cloning and characterization of the rat P2Y4 receptor.

Degenerate PCR was used to amplify DNAs encoding members of the P2Y receptor family from rat brain RNA. A full-length sequence obtained for one novel clone (R5) contained an intronless open reading frame that encoded a polypeptide of 361 amino acids, sharing 84% sequence identity with the human P2Y4 receptor. When R5 was stably expressed in Jurkat cells, calcium fluxes resulting from stimulation of the receptor showed that UDP, ADP, 2-methylthio-ATP, and diadenosine tetraphosphate were inactive, whereas UTP and ATP were both full agonists with similar potency. At the human receptor, ATP has significantly lower potency than UTP. The R5 transcript was not detected in brain by northern hybridization. Therefore, its tissue distribution was assessed by PCR, and the mRNA was found to be widely distributed at a low abundance, being present in brain, spinal cord, and a variety of peripheral organs. Localization of the receptor transcript in adult rat brain sections by in situ hybridization indicated that it is expressed at highest levels in the pineal gland and ventricular system. It is presumed that R5 is a species orthologue of the human P2Y4 receptor but with this significant difference in agonist pharmacology.

Amino Acid Sequence↗
PubMed1998

Evaluation of a sexual abuse prevention program for adults with mental retardation.

Programs to teach sexual abuse prevention skills to persons with mental retardation have rarely been evaluated empirically, and typical evaluations are limited to assessment of the participants' knowledge rather than their performance of specific skills. In the present study, 6 adult women with mental retardation were trained in sexual abuse prevention, and performance was assessed using four separate measures: pretests and posttests of knowledge, verbal report, role play, and naturalistic probes. All women learned the skills but failed to exhibit them to criterion during the probes. We discuss the implications for further training and assessment of sexual abuse prevention skills.

Adult↗
PubMed1997

Acquisition of resistance against Fasciola gigantica by Indonesian thin tail sheep.

The plasma levels of GLDH and the dynamics of development of the numbers of surface lesions on livers, and numbers of parasites, within two to three weeks of a challenge infection, indicated that the major component of the high resistance of Indonesian thin tail (ITT) sheep against Fasciola gigantica was acquired, and acted against juvenile parasites. Few parasites reached the livers of ITT (exposed) sheep, but many had been inhibited, probably in the wall of the jejunum. ITT (naive) sheep showed some resistance, compared with control Merino sheep, by three weeks after infection. Manifestation of the resistance of ITT (exposed) sheep was suppressed by administration of the immunosuppressant, dexamethasone. Killing of parasites in ITT sheep appeared to have ceased by 21 to 28 days after infection. The basis of the acquired resistance was deemed to be an exceptional immunological capacity of ITT sheep responding to an antigen, or an immunological suppressant, peculiar to F. gigantica. That molecule, produced by juvenile parasites, warrants further study as a candidate for a vaccine.

Animals↗
PubMed1997

Impaired spatial information processing in aged monkeys with preserved recognition memory.

Spatial information processing was examined in a non-human primate model of cognitive aging, using procedures formally similar to tasks designed for rats. The test apparatus was a large open field containing eight reward locations. Monkeys rapidly learned to visit each location once per trial, and probe manipulations confirmed that young animals navigated according to the distribution of cues surrounding the maze. In contrast, aged monkeys solved the task using a response sequencing strategy, independent of extramaze spatial information. Object recognition memory was normal in the aged group. The results reveal substantial correspondence in the cognitive effects of aging across rat and primate models, and they establish appropriate procedures for testing the long-standing proposal that the role of the hippocampus in normal spatial learning is similarly conserved.

Aging↗
PubMed1997

Reproductive senescence predicts cognitive decline in aged female monkeys.

The present investigation provide evidences from a non-human primate model that naturally occurring menopause predicts a prominent signature of age-related cognitive decline. Young and aged rhesus monkeys were tested on a delayed response (DR) task known to the sensitive to aging, and reproductive status was evaluated according to menstrual cyclicity and urinary hormone profiles. Peri-/postmenopausal monkeys exhibited significant DR impairments relative to either age-matched premenopausal females, or young control subjects. In addition, markers of endocrine decline in the aged animals were selectively correlated with behavioral performance measures that distinguished premenopausal and peri-/postmenopausal monkeys. These results document that menopause is coupled to cognitive decline in the monkey, and they establish a valuable primate model for defining the effects of endocrine aging on brain and behavioral function.

Aging↗