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Biomedical subjects

J A Roberts

Publications and source records attributed to J A Roberts.

At least 145 records · Page 8Linked to original sources
PubMed1993

Epidermal growth factor receptor expression in three different human endometrial cancer cell lines.

BACKGROUND: The aim of the current study was to establish the characteristics of the epidermal growth factor (EGF) receptor in endometrial cell lines to determine the possible relation of EGF to endometrial cancer. METHODS: Three different cell lines were used: RL95-2 (derived from a moderately differentiated adenosquamous carcinoma), HEC-I-A (from a moderately differentiated adenocarcinoma), and KLE (from a poorly differentiated adenocarcinoma). The binding of (125-I) EGF to these cell lines and the stimulatory effect of EGF on (3H) thymidine incorporation into DNA were examined. RESULTS: EGF receptor was present in all three cell lines. The binding of 125-I-labeled EGF was saturable and of high affinity. Scatchard analysis of the competitive binding data for KLE, HEC-I-A, and RL95-2 revealed linear plots, indicating a single class of binding sites with almost identical equilibrium dissociation constants (0.34 nM, 0.23 nM, and 0.20 nM, respectively). Other peptides, such as insulin-like growth factor (IGF) I and II and insulin, did not compete for the receptor. RL95-2 cells bound significantly more EGF (P < 0.005) than did the HEC-I-A and KLE cell lines. EGF increased 3H-thymidine incorporation in all three cell lines. CONCLUSION: Because EGF receptors are expressed by all three cell lines at markedly different levels and because EGF stimulates 3H-thymidine incorporation into DNA in the three cell lines, the current study suggests that EGF may play a role in the promotion of growth endometrial adenocarcinoma.

Cell Division↗
PubMed1993

[Contribution of experimental pathology to the understanding of human pyelonephritis].

The close similarities between the urinary tract of primates make it possible to use the monkey as a model for understanding the pathophysiology of pyelonephritis in the human. Basically, experimental protocols consist in introducing uropathogenic strains of E. coli into the bladder and/or the ureter in the monkey and to determine early and late consequences of the subsequent renal tissue infection. Lesions appear within the first minutes of bacterial invasion. They result from the virulence of the parasite, which pertains to multiple factors, with a prominent role of fimbrial adhesion. However, the defense mechanisms of the host better explain the renal tissue insult. They comprise early ischoemia due to granulocyte aggregation within the renal capillaries, followed by damage due to oxygen free radicals which are generated during reperfusion. The primate model of pyelonephritis is extremely useful to understand most clinical, functional and radiological events observed in the course of human pyelonephritis. This model also serves to test pharmacological manoeuvres aimed at preventing the renal tissue injury of pyelonephritis.

Animals↗
PubMed1993

Prognostic significance of DNA content and nuclear morphology in borderline ovarian tumors.

We used the technique of image analysis to simultaneously measure DNA content and nuclear morphology of 21 borderline ovarian tumors. Aneuploidy was identified in 9 of 21 tumors and was unrelated to tumor stage or nuclear grade. Morphometric nuclear features that were measured included size, shape, texture, and average density. Nuclear size and shape were positively correlated (r = 0.507), and nuclear size and average density were negatively correlated (r = -0.772). Six tumors recurred and recurrence was significantly associated with tumor aneuploidy (P = 0.046), stage III tumors (P = 0.03), and increased nuclear texture (P = 0.07). These results suggest that measurement of DNA ploidy and nuclear morphology using image analysis can provide important prognostic information in patients with borderline ovarian tumors.

Aneuploidy↗
PubMed1993

Mitogenic activity of growth factors in the human endometrial adenocarcinoma cell lines HEC-1-A and KLE.

Endometrial adenocarcinoma is the most common gynecologic malignancy occurring in the United States. Evidence is accumulating that links peptide growth factors with malignant proliferation. Epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) are known mitogens for endometrial adenocarcinoma in vitro. However, the biological activity of other growth factors in this malignancy is unclear. This study was undertaken to determine the influence of growth factors on the mitogenic activity of the human endometrial adenocarcinoma cell lines HEC-1-A and KLE. Incubation with EGF, IGF-I, insulin-like growth factor II (IGF-II), or insulin stimulated a time-dependent mitogenic response in both cell lines, with the peak response occurring at 24 hr for HEC-1-A and 48 hr for KLE. After two doubling intervals, the number of HEC-1-A cells was increased 3.5-fold by EGF (100 ng/ml), 2.7-fold by IGF-I (100 ng/ml), 2.3-fold by IGF-II (100 ng/ml), and 2.2-fold by insulin (1000 ng/ml) when compared to untreated controls (P < 0.05). The number of KLE cells was increased 2.6-fold by EGF (100 ng/ml), 2.3-fold by IGF-I (100 ng/ml), 2.1-fold by IGF-II (100 ng/ml), and 2.0-fold by insulin (1000 ng/ml) when compared to untreated controls (P < 0.05). Similar results were obtained when DNA content was measured. PDGF failed to stimulate any mitogenic response in either cell line at all concentrations tested (0.1-100 ng/ml). These findings suggest that EGF, IGF-I, IGF-II, and insulin may play a regulatory role in the proliferation of endometrial adenocarcinoma.

Adenocarcinoma↗
PubMed1993

Primary treatment of stage III ovarian carcinoma with sequential chemotherapy and whole abdominal radiation therapy.

A prospective phase II clinical treatment trial of 13 patients with previously untreated optimal surgically resected (< or = 1 cm stage III ovarian carcinoma was conducted at the University of Michigan Hospitals. The treatment regimen after surgical resection consisted of chemotherapy followed by whole abdomen and pelvic radiation therapy. Chemotherapy consisted of four cycles of 50 mg/m2 cisplatin and 1000 mg/m2 cytoxan. This was followed by whole abdomen radiation therapy with a planned total dose of 30 Gy to the whole abdomen and then a 20-Gy boost to the pelvis. Six of 13 patients received a paraaortic radiation boost. There was minimal acute toxicity, but delayed toxicity was encountered with 38% of patients developing a bowel obstruction. Nine patients had reassessment laparotomy: 5 second-look laparotomies and 4 laparotomies for bowel obstruction. Two of these 9 patients died of septic complications after surgery. Nine patients died with disease, 1 patient is alive with advanced disease, and only 3 patients are alive with no evidence of disease. Actuarial 3-year survival and progression-free interval was 26 and 20%, respectively. Primary treatment consisting of sequential chemotherapy and whole abdomen radiation in the dose and scheme utilized did not improve the survival over what could be expected utilizing one of these treatments alone. It was associated with increased delayed toxicity.

Abdomen↗
PubMed1993

Identification and characterization of a proline-rich mRNA that accumulates during pod development in oilseed rape (Brassica napus L.).

Pod development in oilseed rape (Brassica napus) culminates in a process known as dehiscence (shatter) which can result in the loss of seed before the crop is harvested. In order to investigate the biochemical and the genetic basis controlling this process, a cDNA library was constructed from the dehiscence zone of developing pods. This resulted in the isolation of a cDNA clone (SAC51). The mRNA encoded by SAC51 had a transcript size of ca. 700 nucleotides and was found, by northern analysis, to accumulate preferentially in the dehiscence zone of the pod and in no other part of the plant analysed. The predicted polypeptide is rich in the amino acids proline (14.2%) and leucine (14.2%). The sequence of the polypeptide has more than 40% amino acid sequence identity with polypeptides isolated from carrot embryos, maize roots, soybean seeds and young tomato fruit. The function of these proteins is unknown. Genomic Southern analysis suggests that SAC51 is encoded by a single gene or small gene family. The role of the peptide in the development of pods of oilseed rape is discussed.

Amino Acid Sequence↗
PubMed1993

Changes in seminal fluid zinc during experimental prostatitis.

Patients with prostatitis have been found to have decreased prostatic fluid zinc (PF Zn). It is unclear whether changes of prostatitis are due to an inherent lack of Zn in some patients or whether the changes, including reduced PF Zn, are due to the infectious process itself. Six nonhuman primates were infected with 1 x 10(5) E. coli JR340, a clinical isolate known to cause prostatitis in the monkey. After infection, seminal fluid for culture and zinc assay was obtained by electroejaculation. Zinc was measured by colorimetric analysis. Blood counts, quantitative renal scans and urine cultures were also monitored. The animals were followed for 4 weeks and then sacrificed. The histopathology showed resolving prostatitis and fibrosis. Zinc levels dropped with acute infection, and variably recovered as the infection cleared. Controls showed slight variability with respect to PF Zn. It appears that PF Zn decreases as a result of the infectious process.

Animals↗
PubMed1993

Feed resource base for scavenging village chickens in Sri Lanka.

The productivity of a population of scavenging village chickens in Sri Lanka has been assessed, and the scavenging feed resource base has been measured and analysed. The laying period lasted 34 +/- 13 days and the batch size was about 20 eggs. The households ate 71% of the egg production. The mean egg weight was 48 g and the mean size of a set of eggs was 9.4. The hatching percentage was 67 +/- 32 and the liveweight at 70 days averaged 313 g with a range of 142 to 492, by which time 65% of the chicks hatched had died. The age at first lay averaged 211 days when the pullets weighed 1,160 g. The broody period lasted from 3 weeks to 4 months depending on whether the hen hatched eggs, and for how long she tended the brood. The laying hens were actively scavenging for most of the daylight hours. The average amount of scavenged feed per household flock per day was 550 g dry weight with a proximate composition of 9.4% crude protein, 9.2% ether extract and 5.4% crude fibre. More than 70% of the feed intake was household refuse (27% cooked rice, 30% coconut residue, 8% broken rice and 36% other scraps). The remainder was from the environment (13% grass shoots, 8% small metazoans and 7% paddy rice). Proximate analyses of crop contents, household refuse and its major components were carried out. Dietary Ca and P levels were low in the village, as were plasma levels of these minerals. On a balanced commercial diet plasma Ca was still lower than that of hybrid commercial chickens. Suggestions are made for improving the productivity of the scavenging system with no requirement for inputs, and with inputs.

Animal Feed↗
PubMed1993

Synchronous dual primary ovarian and endometrial carcinomas.

OBJECTIVES: The synchronous occurrence of carcinoma confined to the ovary and endometrium presents a diagnostic and therapeutic dilemma. These tumors have been variously staged as FIGO Stage IIA ovarian carcinoma, Stage III endometrial carcinoma, or synchronous dual primary carcinomas. Accumulating evidence suggests such patients have a favorable outcome. This retrospective study was undertaken to review our experience with these fascinating tumors. METHODS: The clinical records and the pathologic findings of 16 patients with synchronous dual primary ovarian and endometrial carcinomas were reviewed. RESULTS: The median age was 51 years. Abnormal uterine bleeding was the most common presenting symptom (70%). All patients had Stage I ovarian and endometrial carcinomas. Fourteen patients (88%) had endometrioid carcinoma in both sites, while two patients (12%) had dissimilar histology. For 15 patients (94%), the grade of both tumors was identical. Only three (19%) patients had myometrial invasion, with less than 50% involvement in each case. All patients underwent surgical staging, 11 (70%) of whom received adjuvant radiation or chemotherapy. The five patients treated with surgery alone had Grade 1 endometrioid tumors. The only relapse occurred in a patient with a clear cell component in both sites. No patient has died of disease. CONCLUSIONS: Patients with synchronous dual primary carcinomas appear to have a more favorable prognosis than that expected with Stage IIA ovarian or Stage III endometrial carcinoma (100% vs. 63% or 42% survival at 3 years, respectively). The excellent survival for patients with Grade 1 dual endometrioid tumors treated with surgery alone suggests that adjuvant therapy may not be necessary for this sub-group.

Adult↗
PubMed1993

Adherence to urethral catheters by bacteria causing nosocomial infections.

Previous clinical studies of catheters with hydrophilic coating have, in some instances, shown a delay in the onset of significant bacteriuria, while others reported no such effect. To attempt to determine reasons for these differences we decided to study bacterial adherence of bacteria obtained from nosocomial urinary tract infections associated with catheters. Almost all strains adhered to the silicone catheter and none of them adhered to the catheter with the hydrophilic surface whether incubated in urine or serum. When incubated in urine, all strains adhered to the red rubber catheters. Adherence was variable to the Teflon and elastomer surfaces.

Bacterial Adhesion↗
PubMed1993

Events leading to septic death from experimental acute pyelonephritis in the monkey.

Experimental acute pyelonephritis in monkeys led to death in some of the animals following renal E. coli inoculation. It was found that both the inflammatory response and cytokine activation were much more severe in these monkeys as compared with others that survived. IL-1 was decreased just before death, and there were early increases in IL-2 and IL-6 serum concentrations, but no significant increase in TNF values. The data suggest that death in sepsis is due in part to excessive cytokine release because of a decrease in the protective activity of IL-1.

Acute Disease↗
PubMed1993

Epidemiology of cercopithecine herpesvirus 1 (B virus) infection and shedding in a large breeding cohort of rhesus macaques.

The epidemiology of B virus infection in a large (n = 157) cohort of rhesus macaques at the California Regional Primate Research Center was evaluated prospectively from September 1989 through January 1991 by serial physical examinations, a behavioral substudy (n = 51), and repeated diagnostic testing. Half were B virus antibody-positive at baseline; subsequently, incident cases of infection were documented through serology alone (42) or with virus isolation (5). Eight recurrent infections and a single symptomatic (primary) case were observed. Risk of B virus infection increased as monkeys aged, with few > 3 years old remaining uninfected. Postpubertal monkeys and those entering sexual adolescence (2-3 years) were at greatest risk, although wounding by cagemates and breeding history (for females) were both significant predictors of time to infection. B virus was isolated from oral or conjunctival and genital tissues in equal proportions. Transmission occurred only during the breeding season, possibly coinciding with an elevation in social stressors in the population.

Animals↗
PubMed1993

Managing markets.

This paper considers the management of markets in the context of the reformed National Health Service (NHS). There are three facets to managing markets: regulating and monitoring markets to ensure that they are competent, managing contracts, and managing agents. The paper considers issues concerned with market structures and entry to and exit from markets; the concept of opportunism is used to explore ways in which self-interested behaviour can operate for good or bad in the setting up of contracts for health care; and factors related to motivating and monitoring agents. The difficulties involved in managing markets are reviewed, and Enthoven is criticized for adopting an over-simplified approach to market management and the abilities of collective agents. The paper concludes by raising questions about the way in which markets are at present being managed in the NHS, and the accountability of purchasers for health care provided and the money spent.

Contract Services↗
PubMed1993

Prevention of renal scarring from pyelonephritis in nonhuman primates by vaccination with a synthetic Escherichia coli serotype O8 oligosaccharide-protein conjugate.

Rhesus monkeys were vaccinated with a synthetic Escherichia coli serotype O8 oligosaccharide-protein conjugate. Using our experimental pyelonephritis monkey model, we tested whether such immunization was protective against the renal damage from inflammation following experimental infection with a P-fimbriated O-antigenically homologous E. coli strain. The vaccination did not significantly alter the duration of bacteriuria or interfere with the infection. However, the vaccine was efficient in renal protection, as vaccinated animals showed significantly less intratubular infiltration of neutrophils (P < 0.02) and the degree of renal scarring was also significantly less in these animals (P > 0.005) than in the control animals. Total kidney involvement in the vaccinated animals was 16.9%, compared with 32.5% in the control animals (P = 0.07).

Animals↗
PubMed1993

Protective anti-idiotype antibodies in the primate model of pyelonephritis.

The adherence of P-fimbriated Escherichia coli to a receptor containing alpha-D-Gal-(1-4)-beta-D-Gal (Gal-Gal) on urothelial cells is an important pathogenic mechanism in the development of pyelonephritis. Antibodies (Ab1) that had been produced by immunization with Gal-Gal conjugated with bovine serum albumin were specifically purified and used to stimulate the production of anti-idiotypic antibodies (Ab2) in cynomolgus monkeys (Macaca fascicularis). While sera from all of the Ab2-producing monkeys contained antibodies reactive with Ab1 and P-fimbriae, not all of the sera inhibited P-fimbrial binding to the Gal-Gal receptor. On the basis of the inhibition of binding, Ab2-producing monkeys were divided into two groups, termed reactive and nonreactive. The reactive and nonreactive Ab2-producing monkeys, together with a group of control monkeys, were challenged with a renal inoculation with P-fimbriated Escherichia coli. Hematologic, immunologic, microbiologic, and pathologic data were compared among the three groups. The reactive monkeys, whose Ab2 in serum inhibited binding between P-fimbriae and the Gal-Gal receptor, were protected against renal damage compared with the control group. The nonreactive group shared some parameters with the reactive group but overall developed renal damage comparable to that of the controls.

Animals↗
PubMed1992

Interleukin 4 is localized to and released by human mast cells.

Recent attention has focused on the T helper type 2 (Th2) lymphocyte as a source of interleukin 4 (IL-4) in allergic disease. However, Th2 cells themselves require a pulse of IL-4 to initiate this synthesis. Here we provide immunohistochemical evidence of IL-4 localization to human mast cells of the skin and respiratory tract, and demonstrate that immunoglobulin E-dependent stimulation of purified human lung mast cells leads to the rapid release of IL-4 into the extracellular environment. We propose that mast cell activation in an allergic response provides a rapid and local pulse of IL-4 into the local environment essential for the triggering of T lymphocytes into sustained IL-4 production and to initiate inflammatory cell accumulation and activation.

Culture Techniques↗