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Biomedical subjects

R Leake

Publications and source records attributed to R Leake.

At least 37 records · Page 2Linked to original sources
PubMed1990

Estrogen and progesterone receptors in ovarian cancer.

To determine whether steroid hormone receptor expression is clinically relevant in ovarian cancer, cytoplasmic and nuclear estrogen (ER) and progesterone (PR) receptor levels have been measured and their concentration calculated by Scatchard analysis. Of 89 samples from patients with non-pretreated epithelial ovarian cancer, 33% were ER-positive, PR-positive (ER+PR+) and 40% ER-negative, PR-negative (ER-PR-); 20% were ER+PR-, and 7% ER-PR+. There was no correlation between receptor status and patient age, menopausal status, or tumor grade, although serous tumors were more likely to be ER+. The incidence of PR+ tumors was highest in early disease and decreased with increasing International Federation of Gynecology and Obstetrics (FIGO) stage. Survival of patients with advanced disease (FIGO Stages IIC, III, or IV) was significantly prolonged by optimal initial cytoreductive surgery (P = 0.002), platinum therapy (P = 0.003), and tumor expression of PR (P = 0.009). On multivariate analysis, PR positivity was still associated with improved survival, although this did not retain statistical significance (P = 0.09).

Adult↗
PubMed1990

Fecapentaene excretion: aspects of excretion in newborn infants, children, and adult normal subjects and in adults maintained on total parenteral nutrition.

People in developed nations such as the United States and Canada have an increased risk of colon cancer. Fecal mutagens have been detected in the feces of individuals at high risk for colon cancer. We describe a rapid, sensitive, reliable, reproducible high-pressure liquid chromatography (HPLC) method for detecting fecapentaenes, the most active and chief mutagen found in human stool. We found fecapentaene in all the stool samples of adults on typical high-fat, low-fiber Western diets. These fecapentaene concentrations remained largely constant when subjects consumed constant diets. Fecapentaene concentrations were reduced for total-parenteral-nutrition (TPN) patients with severe intestinal malabsorption. This finding with TPN patients may reflect changes in important variables of gut microflora in fecapentaene production. Studies with newborns and children showed that fecapentaenes appeared very early in life but are not present in stool at birth.

Adult↗
PubMed1990

Androgen receptors--a method to measure functional behaviour in human prostatic cancer.

Androgen receptors were measured in soluble and nuclear fractions of tissues obtained from 25 patients. A method using mibolerone, a synthetic androgen, as a ligand is described. This method, which includes the presence of excess ORG 2058 to eliminate interaction with progesterone receptors, gives a reliable determination of androgen receptor content and has been used to predict response to hormonal treatment. However, the results suggest that the presence of functional receptor is not, in itself, a sufficient index of hormonal dependence of the tumour.

Aged↗
PubMed1989

Do multiple oestrogen receptor assays give significant additional information for the management of breast cancer?

In 101 breast cancer patients, measurement of oestrogen receptor status in multiple biopsies across a tumour reveals a highly significant difference in the proportion of patients remaining either disease-free (P less than 0.04) or alive (P less than 0.005), when those with uniformly receptor positive (++) primary tumours are matched with clinically comparable patients whose tumours were homogeneously receptor negative (--). Mean follow-up time was 85 months. The prognostic value of this discriminant is particularly striking in the 53 patients with involved nodes at presentation. Of these, 13 were (++) and seven remain alive of whom six are disease-free, whereas 24 of the 29 (--) patients are dead. These results further suggest that receptor assay on a single homogenate gives less clinical information than do assays on multiple biopsies across the tumour. For patients with involved nodes, clinical management may best be decided after determination of 'macroheterogeneity'.

Breast Neoplasms↗
PubMed1989

The cytostatic effects of alpha-interferon may be mediated by transforming growth factor-beta.

There is some evidence to suggest that transforming growth factor-beta (TGF-beta) mediates the cytostatic effects of the anti-oestrogen tamoxifen. In this study we have demonstrated that alpha-interferon has a significant anti-proliferative effect on the oestrogen receptor-positive human breast cancer cell line ZR-75. There is decreased phenotypic expression of the oestrogen receptors (to about 30% of control values) and increased TGF-beta mRNA. Under the growth conditions used here, ZR-75 cells had approximately 5800 TGF-beta binding sites per cell, with an apparent dissociation constant of 70 pm, and we have shown that the anti-proliferative effects of alpha-interferon can be reduced by 60% by co-treating the cells with a TGF-beta polyclonal antibody. The cytostatic effects of alpha-interferon may therefore be mediated by TGF-beta in this human breast cancer cell line.

Antibodies↗
PubMed1988

Progress in understanding breast cancer: epidemiological and biological interactions.

Little progress has been made recently in our understanding of the epidemiology of breast cancer. While results from epidemiologic studies regarding reproductive factors remain fairly reproducible from one study to another, other associations such as that between breast cancer risk and dietary fat intake, although biologically plausible, are not consistently found in direct study of humans, while yet other associations, which appear less plausible biologically, become stronger (such as the increased risk associated with modest levels of alcohol consumption). In this paper we attempt to review the epidemiology and biology of breast cancer jointly and describe possible mechanisms of breast cancer induction, the cellular composition of the breast, the epidemiology of breast cancer, and salient biological features, and attempt to reconcile the biology and epidemiology. It becomes obvious that future progress depends on better biological thinking by epidemiologists, and vice-versa. Areas of further research are suggested and discussed, concluding that the ability to measure diet with greater precision could have an important role to play in clarifying our understanding of breast cancer.

Breast Neoplasms↗
PubMed1988

Indomethacin and patent ductus arteriosus: effects on renal function in preterm lambs.

To examine the independent effects of a patent ductus arteriosus and of indomethacin therapy on the renal function of the preterm newborn, we created a preterm lamb model in which ductus diameter could be regulated. We studied 24 preterm newborn lambs. Eight lambs (group 1) had their ductus closed at delivery and received no indomethacin. Eight lambs (group 2) had their ductus closed and then received indomethacin (0.3 mg/kg) at 5.5 h; eight lambs (group 3) had their ductus kept open and then received indomethacin at 5.5 h. Hemodynamic and renal function measurements were made at 5 h (pretreatment) and at 12.5 h. In group 2 lambs there was a significant reduction in inulin clearance (GFR) and osmolal clearance after indomethacin. In contrast, lambs with an open ductus (group 3), when compared with lambs with a closed ductus (groups 1 and 2) at 5 h, already had significantly decreased blood pressure, GFR, urine volume, and osmolal clearance. Following indomethacin treatment, group 3 lambs showed no further decrease in renal function. We suggest that in preterm lambs with patent ductus, the apparent lack of renal dysfunction following indomethacin treatment reflects underlying diminished renal function.

Animals↗
PubMed1986

IgG and IgG subclass specific antibody responses to diphtheria and tetanus toxoids in newborns and infants given DTP immunization.

To evaluate immune responses to diphtheria and tetanus toxoids in infants we used enzyme-linked immunosorbent assays to detect total IgG and specific IgG-1, IgG-2, IgG-3, and IgG-4 antibody. One group of infants received a newborn dose and subsequently received the usual three doses of DTP. A second group of infants received only the routine dosage at 2, 4, and 6 months of age. In sera acquired at birth, 6, and 9 months of age, there were no statistically significant differences between the two vaccine groups in IgG antibody responses to diphtheria or tetanus, or in IgG subclass tetanus-specific antibody responses. In individual children, tetanus-specific subclass responses were similar in pattern to that for total IgG tetanus antibody, i.e. each IgG subclass response appeared to be regulated by similar mechanisms in that child, but the regulation differed between children. In contrast to a prior study of pertussis immunity, maternally acquired antibody did not significantly affect immune responses to diphtheria or tetanus toxoid by 9 months of age. There was no discernible tolerance due to early tetanus or diphtheria immunization or to high levels of maternally acquired antibody.

Antibodies, Bacterial↗
PubMed1984

New storage procedure for human tumor biopsies prior to estrogen receptor measurement.

Breast tumor biopsies required for steroid receptor determination are normally frozen in liquid nitrogen and stored until assay. However, some limitations of this type of storage exist. To try to both eliminate the need for liquid nitrogen and as part of a study of serial assays on a single tumor biopsy, alternative storage media were investigated. This study shows that storage of breast tumor biopsies at -20 degrees in sucrose buffer made 50% in glycerol prevented the tissues from freezing, yet retained the specific estrogen receptor content both quantitatively and in terms of molecular form (8S:4S ratio). Receptor was stable for up to 100 days, and individual samples could be successfully reassayed throughout this period. Forty-four biopsies from 40 patients were halved, and one section from each was stored in liquid nitrogen, while the other was stored in sucrose:glycerol. Overall, the correlation of receptor content between the two storage methods was good. Using a clinical cutoff value of 20 fmol/mg cytosol protein, only one sample of the 44 would have been classified differently after storage in the two media. Progesterone receptor in biopsies stored in sucrose:glycerol also appears to be stable for at least a limited period.

Biopsy↗
PubMed1976

Stimulatory and inhibitory effects of estrogen on uterine DNA synthesis.

The induction of long-term responses in the uterus following estrogen treatment is discussed, with special reference to DNA synthesis. Immature female rats injected daily with estradiol-17beta or estriol (0.01 to 1 mug) or a combination of the two steroids for one, two or three consecutive days were sacrificed at intervals from 12 to 24 h after the last injection of vehicle or steroid. In vitro incorporation of [3H]thymidine into DNA [14C]leucine into protein, and oxidation of [14C)glucose to 14CO2 were determined. Nuclear-bound estradiol was determined by use of exchange assay or following incubation of intact uteri with 1 X 10(-8)M ([3H]estradiol for 1 h at 37 C. Injection of estriol only partially stimulated DNA synthesis by 18 to 24 h post-treatment. However, injection of estriol followed by injection of estradiol 6 h later resulted in increased DNA synthesis, suggesting that estrogen must be present for up to 6 h to induce subsequent DNA synthesis. Maximal DNA and protein synthesis and oxidation of glucose occurred at 24 h after injection of estradiol (0.1 or 1 mug) but was depressed to control levels by 24 h after the last of three daily injections. Daily injections of 0.01 mug of estradiol resulted in a similar pattern of DNA synthesis, although of lesser magnitude than that observed after injection of 0.1 or 1 mug of estradiol. However, if rats receiving daily injections of 0.01 mug estradiol were challenged with a higher dose of estradiol (1 mug), uterine DNA synthesis was markedly increased. The data suggest that prolonged exposure to estrogen causes uterine cells to become metabolically "refractory" to further estrogen stimulation. Sequential injections of estriol (1 mug) or intermittent injections of estradiol (1 mug) were ineffective in causing this uterine "refractoriness". Receptor binding of estrogen, translocation to the nucleus, and retention of receptor in the nucleus were not affected by sequential estrogen treatment. The accumulation of an inhibitory product is suggested as a possible explanation for this phenomenon.

Animals↗
PubMed1975

Metabolic and hormonal studies comparing three parenteral nutrition regimens in infants.

Metabolic and hormonal studies were performed in 6 infants during the first 3 months of life while receiving 3 different types of parenteral nutrition: 1) 20% glucose and a nitrogen source (Dudrick's method) 2) 12% glucose, a nitrogen source and soybean fat emulsion (Intralipid method) and 3) 12% glucose, a nitrogen source and 1% alcohol (Babson's method). All three regimens provided positive nitrogen balance of similar magnitude. The substrate-hormone relationships were appropriate. After parenteral fat free nutrition (primary caloric source glucose) the plasma glucagon levels were significantly lower and the growth hormone levels significantly higher than after the fat emulsion therapy period. The Dudrick and Intralipid methods resulted in a higher caloric intake and weight gain than the Babson method. The former two regimens cannot be completely endorsed, however, since septic and central vein complications are unavoidable with the Dudrick method particularly in the small infant; and the long term effects of intralipid, particularly on the liver are still unknown.

Amino Acids↗
PubMedDate not supplied

A sensitive and robust assay for urokinase and tissue-type plasminogen activators (uPA and tPA) and their inhibitor type I (PAI-1) in breast tumor cytosols.

uPA and PAI-1 are becoming established as amongst the most effective markers of poor prognosis for patients with node-negative breast cancer; tPA is an index of longer survival. This paper describes a sensitive ELISA for the measurement of uPA, tPA and PAI-1 in breast cancer cytosols. The structure of the assay involves coating Ab (sheep alpha-Chicken IgY), catching Ab (chicken alpha-analyte), tagging Ab (rabbit alpha-analyte) and detecting Ab (goat alpha-rabbit IgG) labelled with HRP. The assay has a high degree of accuracy and specificity. Comparison with the American Diagnostic kits shows the results' equivalence for PAI-1 and tPA. For uPA the results of the assay were twice as high. The assay is sensitive and relatively inexpensive. It is the first published assay to yield strictly comparative values for uPA, tPA and PAI-1 in tissue extracts and is readily subject to external quality control.

Animals↗
PubMedDate not supplied

Systemic effects of mydriatics in low weight infants.

Two-and-a-half percent phenylephrine eye drops were used in combination with 0.5% tropicamide for routine pupillary dilation in 10 low weight infants. Significant systolic blood pressure elevation was noted in eight of 10 infants. A matched control group dilated with cycloplegics alone did not show a significant rise in systolic blood pressure. The mean change in pupillary dilation in the study group was 3.9 mm compared with 3.1 mm in the control group. This difference is not statistically significant. We therefore recommend that cycloplegic agents alone be used for pupillary dilation in these high risk infants.

Blood Pressure↗