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Biomedical subjects

J A Roberts

Publications and source records attributed to J A Roberts.

At least 91 records · Page 5Linked to original sources
PubMed1997

Transforming growth factor-beta negatively modulates proliferation and c-fos expression of the human endometrial adenocarcinoma cell line HEC-1-A.

Growth factor regulation of normal and cancerous cell proliferation has been well-documented and may be mediated by proto-oncogene activity. The purpose of this study was to assess changes in proliferation and mitogen-induced c-fos mRNA expression of an endometrial carcinoma cell line, HEC-1-A, in response to TGF-beta, a potent growth-inhibitory peptide. HEC-1-A cells were incubated in the presence or absence of TGF-beta. Mitogen-stimulated cells were additionally treated with epidermal growth factor (EGF). Changes in proliferation were measured by [3H]thymidine uptake assays. Alterations in EGF-induced c-fos expression following TGF-beta pretreatment were assessed by Northern blot using a 32P-labeled human c-fos probe. Finally, chloramphenicol acetyltransferase assays were performed to evaluate c-fos promoter activity in response to treatment conditions. Basal and EGF-stimulated proliferation was inhibited by TGF-beta in a dose- and time-dependent manner. TGF-beta also reversibly decreased EGF-induced c-fos mRNA expression in a dose- and time-dependent manner. Sequences in the c-fos promoter that were stimulated by EGF showed suppressed activity when preincubated with TGF-beta. These results show that TGF-beta negatively modulates EGF-induced c-fos expression, which may be related to the observed inhibition of carcinoma cell proliferation.

Adenocarcinoma↗
PubMed1997

A randomized, multicenter, double-blind, placebo-controlled, dose-finding study of ORG 2766 in the prevention or delay of cisplatin-induced neuropathies in women with ovarian cancer.

OBJECTIVE: The objective was to evaluate the efficacy of Org 2766 (a hexapeptide analogue of ACTH) in the prevention or delay of cisplatin-induced neuropathy during chemotherapy in women with ovarian cancer as measured by vibration perception threshold (VPT). METHODS: In this randomized, multicenter, double-blind, placebo-controlled study, 196 women with ovarian cancer were treated with cisplatin 75-100 mg/m2, cyclophosphamide 600-1000 mg/m2 plus placebo or two dose levels of Org 2766. The cisplatin-induced neuropathies were monitored by determining the VPT with the Vibratron II. VPT was determined for both the most sensitive great toe and the index finger on a monthly basis during treatment and months 1, 2, and 3 postchemotherapy. Once the blind was broken, it was found that 174 women (59 in placebo, 58 in 2 mg, and 57 in 4 mg) had enough data to allow evaluation. RESULTS: Over the course of follow-up, the VPT was found to increase. This is consistent with the development of cisplatin-induced peripheral neuropathies. The baseline VPT for the index finger was less than that of the great toe (0.65 vs 2.13), but the percentage change in VPT was the same for both (percentage increase in VPT of about 350%). When the VPTs are compared according to the dose of Org 2766 given, there appears to be no difference in the rate of change or degree of neuropathies that developed in these women receiving cisplatin and cyclophosphamide. CONCLUSIONS: The development of cisplatin-induced neuropathies is confirmed by measurement of the VPT. The rate of development of neuropathies seems to accelerate after the sixth course of cisplatin. When the development of neuropathies is evaluated on the basis of Org 2766 dosage, it is found that there is no difference in the rate or degree of neuropathies seen. Instead of providing protection from and delay of onset of peripheral neuropathies caused by cisplatin, these results suggest that the administration of Org 2766 appears to cause an increase in the rate of change and degree of neuropathies (P > 0.05).

Adrenocorticotropic Hormone↗
PubMed1997

Factors influencing views of patients with gynecologic cancer about end-of-life decisions.

OBJECTIVE: This study was undertaken to assess the life views, practices, values, and aspirations of women with various stages of gynecologic cancer. STUDY DESIGN: A self-administered questionnaire was completed by 108 women with various stages of cancer and 39 women with benign gynecologic disease. The questionnaire included items on demographics in addition to 16 multiple choice and 4 true-false items. The four questions related to criteria of good care, degree of involvement in decision making, psychosocial well-being, religious experience, and aspirations form the basis of this study. The data were analyzed with the Pearson chi 2 test (Systat, version 5.1) with significance set at p < 0.05. RESULTS: The women in this study placed greatest emphasis on receiving "straight talk" (96%) and compassion (64%) from their physicians. The newly diagnosed group put significantly less emphasis on compassion (33%, p = 0.037). Less than half expected their physicians to cure (43%, 56% for newly diagnosed) or contain (49%) the disease. For these women fear was the most dominant psychosocial consequence of having cancer, with difficulty communicating or feeling abandoned, isolated, or embarrassed less common. Those who specified their ears were afraid of pain (63% vs 39% for patients with benign disease, p = 0.019), dying (56%), losing control (48%), or becoming totally dependent (46%). Seventy-six percent indicated that religion had a serious place in their lives, with 49% becoming more religious since their cancer diagnosis, whereas no one became less religious. Ninety-three percent believed that the religious commitment helped sustain their hopes. CONCLUSIONS: These data suggest that (1) physicians should aim to educate their patients sufficiently for them to exercise control over their experience, to allay their fears, and to make personal decisions that further their aspirations, (2) patients in different stages of disease varied in their perceptions of themselves and their aspirations, (3) patients are dealing with fear as a primary problem, and (4) women with gynecologic cancer depend on their religious convictions and experiences as they cope with the disease.

Adult↗
PubMed1997

Resistance of Indonesian thin tail sheep against Fasciola gigantica and F. hepatica.

High resistance of Indonesian thin tail (ITT) sheep against Fasciola gigantica has been confirmed. Naive ITT sheep had only 17% of the number of mature parasites collected from control St. Croix sheep. In contrast, the level of resistance of ITT sheep against F. hepatica was the same as that of the low resistance Merino breed after both primary and secondary infections. It is suggested that resistance of ITT sheep against F. gigantica was manifested in two phases. The major phase appeared to be specific to the ITT sheep : F. gigantica relationship, acting against immature parasites in both naive and previously exposed hosts and could be innate or acquired. The second phase appeared to be specific to F. gigantica, and was acquired, because it killed young adult parasites only after secondary infection. F. gigantica from ITT sheep were heavier than those from the St. Croix sheep, possible because feeding was impaired by more extensive liver damage in the latter. Approximately 45 F. gigantica killed 25-kg sheep before and during migration from the liver parenchyma into the bile ducts. Death was caused by haemorrhages into the liver parenchyma, bile ducts and peritoneum.

Animals↗
PubMed1997

Evidence for a major gene determining the resistance of Indonesian Thin Tail sheep against Fasciola gigantica.

The genetic basis of the high resistance of Indonesian Thin Tail (ITT) sheep against Fasciola gigantica has been studied by measuring the resistance levels of ITT sheep, St. Croix sheep and their F2 and F3 crossbreds. All of the sheep were bred and reared in the same environment. Approximately half of the F2 and F3 crossbreds were as resistant as the ITT parental breed, one-quarter had the low resistance of the St. Croix parental breed and the rest had an intermediate level of resistance. It is concluded that the high resistance is determined by a major gene with incomplete dominance. The prevalence of the gene in the ITT sheep population is estimated to be about 90%. The resistance may be innate or acquired; but, regardless of the mechanism, it could be used to control fasciolosis caused by F. gigantica by breed substitution or by crossbreeding with other breeds of sheep.

Animals↗
PubMed1997

Economic evaluation of diagnostic technology. Methodological challenges and viable solutions.

The principles of economic evaluation are increasingly accepted by clinicians and policy makers as evidence from a significant number of studies becomes available to support their decisions. However, methods of assessment still need to be improved. This paper reports a comprehensive review of methodological challenges in the economic evaluation of diagnostic technology, where such challenges are more evident. This review formed the basis for a prioritized research agenda, with four main areas: modeling techniques for dealing with complexity; measures of the opportunity cost of shared resources; techniques for eliciting decision makers' utility functions for diagnostic tests; and ways of assessing the robustness of decisions. A number of methodological solutions are proposed, aimed at capturing elements and relationships that are usually neglected and fully recognizing the presence of an inductive cognitive component in decision-making processes.

Cost-Benefit Analysis↗
PubMed1997

Regulation of brain capillary endothelial cells by P2Y receptors coupled to Ca2+, phospholipase C and mitogen-activated protein kinase.

1. The blood-brain barrier is formed by capillary endothelial cells and is regulated by cell-surface receptors, such as the G protein-coupled P2Y receptors for nucleotides. Here we investigated some of the characteristics of control of brain endothelial cells by these receptors, characterizing the phospholipase C and Ca2+ response and investigating the possible involvement of mitogen-activated protein kinases (MAPK). 2. Using an unpassaged primary culture of rat brain capillary endothelial cells we showed that ATP, UTP and 2-methylthio ATP (2MeSATP) give similar and substantial increases in cytosolic Ca2+, with a rapid rise to peak followed by a slower decline towards basal or to a sustained plateau. Removal of extracellular Ca2+ had little effect on the peak Ca2+-response, but resulted in a more rapid decline to basal. There was no response to alpha,beta-MethylATP (alpha,beta MeATP) in these unpassaged cells, but a response to this P2X agonist was seen after a single passage. 3. ATP (log EC50 -5.1+/-0.2) also caused an increase in the total [3H]-inositol (poly)phosphates ([3H]-InsPx) in the presence of lithium with a rank order of agonist potency of ATP=UTP=UDP>ADP, with 2MeSATP and alpha,beta MeATP giving no detectable response. 4. Stimulating the cells with ATP or UTP gave a rapid rise in the level of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), with a peak at 10 s followed by a decline to a sustained plateau phase. 2MeSATP gave no detectable increase in the level of Ins(1,4,5)P3. 5. None of the nucleotides tested affected basal cyclic AMP, while ATP and ATPgammaS, but not 2MeSATP, stimulated cyclic AMP levels in the presence of 5 microM forskolin. 6. Both UTP and ATP stimulated tyrosine phosphorylation of p42 and p44 mitogen-activated protein kinase (MAPK), while 2MeSATP gave a smaller increase in this index of MAPK activation. By use of a peptide kinase assay, UTP gave a substantial increase in MAPK activity with a concentration-dependency consistent with activation at P2Y2 receptors. 2MeSATP gave a much smaller response with a lower potency than UTP. 7. These results are consistent with brain endothelial regulation by P2Y2 receptors coupled to phospholipase C, Ca2+ and MAPK; and by P2Y1-like (2MeSATP-sensitive) receptors which are linked to Ca2+ mobilization by a mechanism apparently independent of agonist stimulated Ins(1,4,5)P3 levels. A further response to ATP, acting at an undefined receptor, caused an increase in cyclic AMP levels in the presence of forskolin. The differential MAPK coupling of these receptors suggests that they exert fundamentally distinct influences over brain endothelial function.

Adenosine Diphosphate↗
PubMed1997

Characterization of the onset of menopause in the rhesus macaque.

The objective of this study was to assess ovarian activity in a cohort of aged female rhesus macaques. Menstrual records for 26 rhesus macaques ages 20-29 yr were evaluated over a 1-yr period, and daily urinary estrone conjugate (E1C) and pregnanediol-3-glucuronide (Hygeia [Hy]-PdG) levels were determined for 12 wk. Each animal was categorized as either pre-, peri-, or postmenopausal based on menstrual and hormonal data. Eleven animals (mean age 22.5 yr) were premenopausal, thirteen (mean age 24 yr) were perimenopausal, and two (mean age 29.5 yr) were postmenopausal. Hormone profiles for perimenopausal animals reveal prolonged follicular phases and/or a lack of patterned Hy-PdG dynamics. Breakthrough bleeding occurred in four of these perimenopausal animals. The postmenopausal animals were amenorrheic and exhibited low E1C levels (less than 10 ng/mg creatinine). The results of this study illustrate that the decline of ovarian function in female macaques during the third decade of life parallels the menstrual and hormonal events associated with the climacteric in women, and that menopause does occur in rhesus macaques.

Aging↗
PubMed1997

Epitopes of the P-fimbrial adhesin of E. coli cause different urinary tract infections.

PURPOSE: This is a study of the interaction of the tip protein of P-fimbriae E. coli, its specific urothelial adhesin, and urothelial receptors for the adhesin. This tip protein has several epitopes that adhere to different isoreceptors containing the urothelial alpha-gal-1-4 beta-gal disaccharide. Renal tubular cells of our monkey model contain the globoside isoreceptor, and thus ureteral inoculation of E. coli with the class II tip protein leads to pyelonephritis. The class III tip protein adheres to the Forssman antigen and causes cystitis in humans. MATERIALS AND METHODS: An E. coli strain, DS17 which originally caused pyelonephritis in a child, is P-fimbriated and contains a class II tip adhesin. A mutant was produced to contain a class III tip adhesin. Eight monkeys had a ureteral inoculation of E. coli DS17 and 4 monkeys with E. coli DS17-1. In addition, we studied in vitro adherence by these strains. RESULTS: We show that in vitro adherence by the tip protein of P-fimbriae to bladder cells of the monkey occurs by several mechanisms, adhering to specific receptors for the class II and III epitopes of the tip protein as well as by means of type 1 fimbriae. In addition, the PapE protein of the fibrillum of the P-fimbriae adheres to fibronectin. As always, electrostatic and hydrophobic interaction remain important contributions to adherence. E. coli DS17 caused pyelonephritis, but DS17-1 caused cystitis. Bacteriuria was prolonged by DS17 infection. CONCLUSION: The site of a urinary tract infection from P-fimbriated E. coli can be predicted by the epitope of the tip protein of P-fimbriae.

Adhesins, Escherichia coli↗
PubMed1996

Cost effectiveness of treating primary care patients in accident and emergency: a comparison between general practitioners, senior house officers, and registrars.

OBJECTIVES: To compare outcome and costs of general practitioners, senior house officers, and registrars treating patients who attended accident and emergency department with problems assessed at triage as being of primary care type. DESIGN: Prospective intervention study which was later costed. SETTING: Inner city accident and emergency department in south east London. SUBJECTS: 4641 patients presenting with primary care problems: 1702 were seen by general practitioners, 2382 by senior house officers, and 557 by registrars. MAIN OUTCOME MEASURES: Satisfaction and outcome assessed in subsample of 565 patients 7-10 days after hospital attendance and aggregate costs of hospital care provided. RESULTS: Most patients expressed high levels of satisfaction with clinical assessment (430/562 (77%)), treatment (418/557 (75%)), and consulting doctor's manner (434/492 (88%)). Patients' reported outcome and use of general practice in 7-10 days after attendance were similar: 206/241 (85%), 224/263 (85%), and 52/59 (88%) of those seen by general practitioners, senior house officers, and registrars respectively were fully recovered or improving (chi2 = 0.35, P = 0.840), while 48/240 (20%), 48/268 (18%), and 12/57 (21%) respectively consulted a general practitioner or practice nurse (chi2 = 0.51, P = 0.774). Excluding costs of admissions, the average costs per case were 19.30 pounds, 17.97 pounds, and 11.70 pounds for senior house officers, registrars, and general practitioners respectively. With cost of admissions included, these costs were 58.25 pounds, 44.68 pounds, and 32.30 pounds respectively. CONCLUSION: Management of patients with primary care needs in accident and emergency department by general practitioners reduced costs with no apparent detrimental effect on outcome. These results support new role for general practitioners.

Consultants↗
PubMed1996

Cultured endometrial cancer cells exhibit autocrine growth factor stimulation that is not observed in cultured normal endometrial cells.

OBJECTIVE: To evaluate the autocrine stimulation hypothesis, primary cultures of malignant and normal endometrium were assayed for differences in response to growth factors (GF) GF and receptor blocking antibodies. METHODS: Thirteen normal and 10 malignant endometrial samples were collected. Cells were enzymatically dispersed and maintained in serum-free medium. They were incubated with epidermal GF (EGF), transforming GF-alpha (TGF-alpha), insulin-like GF-I (IGF-1), anti-EGF receptor antibody (Ab528), and anti-IGF-1 receptor antibody (alpha IR3) at physiologic concentrations. Tritiated thymidine incorporation was measured. RESULTS: Malignant endometrial cells increased thymidine incorporation when incubated with EGF (20.75%), TGF-alpha (19.8%), or IGF-1 (32.8%) compared to untreated control cells. When incubated with Ab528 or alpha IR3 antibodies alone, proliferation of malignant cells was inhibited (-12.4 and -23%, respectively, P < 0.003). Normal endometrial cells were inhibited by EGF (-24.9%), TGF-alpha (-25.6%), and IGF-1 (31.9%). Incubation of normal cells with Ab528 and alpha IR3 antibodies stimulated growth (125 and 115%, respectively, P < 0.02). CONCLUSIONS: These data are consistent with the autocrine stimulation hypothesis for neoplastic endometrium and illustrate differences compared to nonneoplastic endometrial growth factor-mediated proliferation.

Antibodies↗
PubMed1996

The practice of surgical staging and its impact on adjuvant treatment recommendations in patients with stage I endometrial carcinoma.

A survey of American gynecologic oncologists was undertaken to assess their compliance with current surgical staging criteria in patients with early endometrial carcinoma. One hundred forty-four members of the Society of Gynecologic Oncologists responded to the survey. Respondents treated an average of 22 new cases annually. Tumor grade and intraoperative determination of depth of myometrial invasion were demonstrated to influence the frequency of lymphatic dissection. In grade 1, 2, and 3 lesions, 76, 60, and 34% of responders, respectively, indicated that depth of invasion influenced their decision to perform lymphadenectomy. In addition, depth of invasion was important in determining type and extent of lymphatic resection. Further, the impact of pathologic lymph node status on postoperative adjuvant radiation therapy recommendations was evaluated for various stratifications of endometrial adenocarcinoma confined to the corpus. The greatest differences in treatment recommendations were noted in the 50-66% invasion category. For grade 1 and 2 cancers, adjuvant therapy recommendations were reduced by 23 and 16% respectively when comparing pelvic and combined therapy versus none and vaginal therapy. The effect of surgical staging data on clinical decisions is clearly evident. The knowledge of pathologically negative lymph node status reduces the recommendation for postoperative adjuvant radiotherapy in patients with adenocarcinoma otherwise confined to the uterine corpus.

Chemotherapy, Adjuvant↗
PubMed1996

A molecular study of dormancy breaking and germination in seeds of Trollius ledebouri.

A cDNA library was generated from seeds of Trollius ledebouri cv. Golden Queen after GA3 treatment. Five clones encoded mRNAs which were down-regulated during dormancy breaking and the initial stages of germination. Two of these showed homology to storage proteins (pPCB3 and pPCB4) and one each to the late-embryogenesis-abundant (LEA) group 2 dehydrin proteins (pPCB2), a barely glucose dehydrogenase (pPCB6) and the glutathione S-transferase (GST) superfamily (pPCB7). Transcript levels declined over 8 days in GA3-treated seeds. In dormant imbibed seeds transcript levels were relatively unchanged over the same period except for the PCB3 transcript, the level of which increased.

Amino Acid Sequence↗
PubMed1996

Acquired resistance of merino sheep against Fasciola gigantica.

Merino sheep acquired resistance against Fasciola gigantica, which is contrary to previous observations of infections with F. hepatica in that breed. The acquired resistance was manifest against young adult parasites. St. Croix sheep had previously been shown to have more resistance than European sheep against F. hepatica after primary infection; however, in F. gigantica infections in the present study there was no difference between the resistance levels of the breeds. Antigenic analysis of the host:parasite relationships could lead to identification of protective antigens suitable for use as vaccines.

Animals↗
PubMed1996

Factors predisposing to urinary tract infections in children.

The normal urinary tract is sterile for many reasons. These include: bacterial eradication by urinary and mucus flow, urothelial bactericidal activity, urinary secretory IgA, and blood group antigens in secretions which interfere with bacterial adherence. Periodic emptying of the bladder should wash bacteria out, but uropathogens grow well in urine and their rapid doubling time might not clear bacteria by voiding at the usual frequency. The ability to colonize the gut, as well as adhere to host squamous and urothelial cells, is due to bacterial adherence, a mechanism by which fluid washout would not be effective. Fimbriae or pili, hair-like surface appendages of Escherichia coli, are the usual adhesins. E. coli with type 1 fimbriae adhere to mucus, and P-fimbriae adhere to glycolipids on mucous membranes and urothelial cells. Other common virulence factors of E. coli include the capsule, which prevents phagocytosis, hemolysin, which damages urothelium, and aerobactin, which sequesters iron. Adherence stimulates the inflammatory response by activation of cytokines such as interleukin-1, -6, and -8. These cytokines stimulate the production of intercellular adhesion molecule, which by leukocyte adhesion causes migration of these cells to the site of infection to counteract it.

Adhesins, Bacterial↗
PubMed1996

Neonatal circumcision: an end to the controversy?

The incidence of urinary tract infections is 10 times higher in the uncircumcised male than in those circumcised. An extensive review of bacterial adherence, the initiating factor in urinary tract infections, is presented to show that bacterial adherence to the prepuce is necessary for pyelonephritis to occur. Colonization with maternal bacteria occurs at birth; thus the incidence of pyelonephritis in infants born of bacteriuric mothers is much higher than it is in infants born of nonbacteriuric mothers. The significant morbidity of acute pyelonephritis in infants is one reason for encouraging neonatal circumcision, but a more important reason is that acute pyelonephritis in the first years of life often leads to significant renal damage that may progress to end-stage renal disease during adolescence. Since circumcision can now be done under local anesthesia, the newborn infant can have a painless prophylactic operation that will prevent urinary tract infections, pyelonephritis, and end-stage renal disease.

Adolescent↗