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J E Ferguson

Publications and source records attributed to J E Ferguson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Expression of parathyroid hormone-related peptide and its receptor messenger ribonucleic acid in human amnion and chorion-decidua: implications for secretion and function.

OBJECTIVE: Our purpose was to define the location and packaging of parathyroid hormone-related peptide in amnion-chorion and the potential target tissues for its action in fetal membranes. STUDY DESIGN: We studied fetal membranes by use of light microscopic immunocytochemistry with three monoclonal antibodies against distinct regions of the parathyroid hormone-related peptide molecule. For electron microscopy immunogold analysis with a monoclonal antibody specific to the 109-141 fragment was used to observe parathyroid hormone-related peptide intracellularly in amnion membrane and in the chorion layers. Multiplex reverse transcriptase-polymerase chain reaction with Southern blotting was used to identify parathyroid hormone/parathyroid hormone-related peptide receptor and control messenger ribonucleic acids in amnion and chorion-decidua. RESULTS: All monoclonal antibodies revealed immunoreactive parathyroid hormone-related peptide in the amniotic epithelial cells and in some fibroblast-like cells embedded in the extracellular matrix of the amnion. Parathyroid hormone-related peptide was also found in the chorion in fibroblast and trophoblast layers and in decidua. Ultrastructurally immunogold particles were evenly distributed throughout the amniotic epithelial cells and were present in apical microvilli and near the basal membranes. Electron microscopy studies of the chorion cytotrophoblast also showed freely dispersed immunogold particles of parathyroid hormone-related peptide with no packaging in secretory granules. Low to undetectable levels of parathyroid hormone/parathyroid hormone-related peptide receptor messenger ribonucleic acid were found in amnion tissue, whereas abundant receptor messenger ribonucleic acid was found in chorion-decidua. CONCLUSIONS: These results suggest the presence of a parathyroid hormone-related peptide paracrine system within the human fetal membranes.

Amnion↗
PubMed1995

Continuous infusion of 5-fluorouracil with alpha 2b interferon for advanced colorectal carcinoma.

Thirty patients with symptomatic colorectal carcinoma were commenced on treatment with 5-fluorouracil (2.5 g week-1) administered by continuous intravenous infusion and alpha 2b interferon (3 x 10(6) U s.c. three times a week). Six out of 30 patients (20%) achieved a partial response. Three patients (10%) had stable disease and 21 patients (70%) progressed on treatment. Twenty patients (67%) completed ten or more weeks of treatment. In nine patients, treatment was withdrawn after 2-9 weeks because of disease progression or death. One patient's treatment was interrupted by emergency surgery. The median survival for all patients was 210 days (7 months). The principal side-effects were oral mucositis (12/30 patients), nausea (8/30 patients) and transient diarrhoea (4/30 patients), and initial constitutional symptoms due to alpha 2b interferon. The combination of low-dose continuous infusional 5-fluorouracil and low-dose alpha 2b interferon is well tolerated but has no obvious advantage over alternative infusional regimens using 5-fluorouracil as a single agent.

Adult↗
PubMed1994

Phenotypic heterogeneity in breast fibroblasts: functional anomaly in fibroblasts from histologically normal tissue adjacent to carcinoma.

Histologically normal breast tissue was obtained from women undergoing surgery for benign breast lesions (n = 12) and mammary carcinomas (n = 15). Four fibroblast subpopulations (FI, FII, FIII and FIV) were isolated from these specimens by differential digestion and centrifugation. FI cells were the first to be released from the tissue digest and consequently assumed to be derived from the interlobular stroma; FIV fibroblasts were tightly associated with the epithelial organoids and are therefore believed to be of intralobular origin. These cells were characterised in terms of their migratory phenotype (classified as either foetal- or adult-like) and the production of motility factors according to previously described techniques. FI fibroblasts obtained from patients with benign breast lesions displayed a foetal migratory phenotype (10/11) and secreted detectable quantities of motility factors (11/11). In contrast, none of the FIV fibroblasts (0/10) obtained from these same patients displayed a foetal-like migratory phenotype or secreted motility factors. In the case of fibroblasts obtained from cancer patients, both FI (13/13) and FIV (13/13) fibroblasts displayed a foetal-like migratory phenotype and secreted motility factors. Fibroblasts were also derived from skin (n = 12) and breast fat tissue (n = 4) of certain patients. In agreement with our previously published observations, skin fibroblasts obtained from non-cancer and cancer patients also differed in terms of their migratory behaviour: none of the skin fibroblast lines (0/5) obtained from non-cancer patients were foetal-like, compared to 3/7 lines from cancer patients. All fat-derived fibroblasts (1 non-cancer and 3 cancer patients) were also foetal-like. Our results indicate (i) functional heterogeneity between FI and FIV fibroblasts of normal breast, and (ii) the presence of functionally aberrant (i.e., foetal-like) FIV fibroblasts in histologically normal breast tissue adjacent to a carcinoma.

Adipose Tissue↗
PubMed1994

Expression of parathyroid hormone-related protein and its receptor in human umbilical cord: evidence for a paracrine system involving umbilical vessels.

OBJECTIVE: Our purpose was to study the expression and localization of parathyroid hormone-related protein and expression of the parathyroid hormone/parathyroid hormone-related protein receptor in human umbilical cord. STUDY DESIGN: The expression and localization of parathyroid hormone-related protein and expression of the parathyroid hormone/parathyroid hormone-related protein receptor were studied in isolated tissues from the human umbilical cord by Northern analysis, reverse-transcriptase polymerase chain reaction, Southern gel analysis, and immunolocalization procedures at the light and electron microscopic levels. RESULTS: Parathyroid hormone-related protein was abundantly expressed in the umbilical cord. Immunohistochemical and immunocytochemical techniques confirmed hormone localization in the amnion epithelial layer and in vascular smooth muscle and endothelial cells in vessels from the umbilical cord and placental chorionic plate. Multiplex reverse-transcriptase polymerase chain reaction identified expression of receptor messenger ribonucleic acid in vessels of the umbilical cord; this finding was verified by means of Southern gel analysis of the products of the reverse-transcriptase polymerase chain reaction. CONCLUSION: A parathyroid hormone-related protein paracrine system appears to exist in human umbilical cord. We suggest that it may be involved in the control of fetal placental circulation.

Endothelium, Vascular↗
PubMed1994

Aquagenic pruritus associated with metastatic squamous cell carcinoma of the cervix.

Aquagenic pruritus has been reported in association with a variety of underlying disorders including polycythaemia rubra vera, myelodysplastic syndrome, the hypereosinophilic syndrome and juvenile xanthogranuloma. However, in most cases the aetiology is unknown. The onset of intractable aquagenic pruritus is reported in a fit 71-year-old lady; however, 10 months later she was found to have hepatic metastases arising from a squamous cell carcinoma of the cervix treated 15 years previously. The occurrence of these two relatively rare conditions is likely to be coincidental. None the less, the close temporal relationship between the onset of aquagenic pruritus and the hepatic metastases raises the possibility of a true association. Aquagenic pruritus may be associated with a wider variety of underlying disorders than previously reported. Intractable symptoms of recent onset in a patient with a past history of cancer should be investigated.

Aged↗
PubMed1994

Attenuation of agonist-induced desensitization of the rat substance P receptor by microinjection of inositol pentakis-and hexakisphosphates in Xenopus laevis oocytes.

Recently, inositol hexakisphosphate (phytic acid) was shown to bind to photoreceptor arrestin and block its interaction with rhodopsin. Such an interaction might predict that inositol polyphosphates could alter G protein-coupled receptor desensitization. To investigate the possible roles of higher inositol polyphosphates on receptor desensitization, we have expressed the rat substance P receptor in Xenopus laevis oocytes. The functional expression of substance P receptor was monitored by voltage-clamp recording of substance P-induced Ca(2+)-dependent Cl- currents. When control oocytes were stimulated with substance P (30 nM), after 10 min of washing the second responses to substance P were approximately 15% of the first responses. Cytosolic injection of inositol pentakisphosphate (100 microM) or inositol hexakisphosphate (100 microM) inhibited the reduction of the second substance P-induced current responses, maintaining the second responses to 57-58% of the initial responses. The protective effects of inositol pentakisphosphate and inositol hexakisphosphate against agonist-induced desensitization were concentration and time dependent and structurally specific, in that inositol hexasulfate and inositol tris- and tetrakisphosphate isomers were inactive. Microinjection of inositol hexakisphosphate did not (a) change the potency of substance P or the sensitivity of the expressed substance P receptor to substance P, (b) inhibit 12-O-tetradecanoylphorbol-13-acetate-induced loss of substance P-induced current responses, or (c) alter the currents elicited by microinjection of inositol-1,4,5-trisphosphate. These results suggest that inositol pentakisphosphate and inositol hexakisphosphate have specific inhibitory effects on the agonist-induced loss of responsiveness of the rat substance P receptor. Moreover, these protective effects of inositol hexakisphosphate against desensitization were also observed with the endogenous lysophosphatidic acid/phosphatidic acid receptor, indicating that this mechanism is not specific to ectopic receptors. These results suggest that inositol pentakisphosphate and inositol hexakisphosphate may be novel pharmacological tools for the study of agonist-induced desensitization.

Animals↗
PubMed1993

Abnormal membranes in obstetrical ultrasound: incidence and significance of amniotic sheets and circumvallate placenta.

Amniotic sheets were identified in ten of 1784 patients having routine obstetric ultrasound scans, giving an incidence of 0.6%. In the same population, findings suggesting circumvallate placenta were seen in three patients, giving an incidence of 0.2%. The overall frequency of finding abnormal membranes projecting into the gestational sac was 0.8% which is an order of magnitude greater than the incidence of amniotic bands, which are only present in up to 0.08% of pregnancies. It is important to distinguish amniotic sheets and circumvallate placenta from amniotic bands, since they are much more likely to be found during the ultrasound examination and need to be properly identified so as to avoid needlessly alarming pregnant patients or inappropriately considering termination of pregnancy for relatively benign entities.

Journal Article↗
PubMed1993

Intraamniotic 15(s)-15-methyl prostaglandin F2 alpha and termination of middle and late second-trimester pregnancy for genetic indications: a contemporary approach.

OBJECTIVE: Our purpose was to determine whether intraamniotic 15(s)-15-methyl prostaglandin F2 alpha could serve effectively and safely as a surrogate for natural prostaglandin F2 alpha when used to effect middle and late second-trimester pregnancy termination for genetic indications. Further, we sought to compare efficacy and side effects with those found when intravaginal prostaglandin E2 is used. STUDY DESIGN: A total of 62 patients received intraamniotic 15(s)-15-methyl prostaglandin F2 alpha and urea, and intracervical laminaria. Case patients at < or = 20 weeks' gestation (n = 32) were compared with case patients at > 20 weeks (n = 30) and with a matched group (n = 64; 1:2 ratio) of control patients in whom cervical laminaria and intraamniotic urea were used with prostaglandin E2 vaginal suppositories. RESULTS: The mean induction-to-abortion interval among the case patients (gestational age 16 to 27 weeks) was 13 hours 11 minutes; 60 of 62 (97%) were delivered within 24 hours. There was a statistically significant negative correlation between the induction-to-abortion interval and gestational age (p = 0.04). When patients at < or = 20 weeks and those at > 20 weeks were compared, few differences were noted. The mean induction-to-abortion interval for case patients at < or = 20 weeks was 13 hours 54 minutes versus 19 hours 34 minutes for control patients (p = 0.001). One of 32 (3%) case patients remained undelivered beyond 24 hours compared with 17 of 64 (27%) control patients (p < 0.01). Immediate and delayed complications were uncommon in either group. CONCLUSION: Our study demonstrates that 15(s)-15-methyl prostaglandin F2 alpha can serve safely as a surrogate for prostaglandin F2 alpha when used in combination with urea and laminaria for termination of pregnancy. This technique appears safe for use through 27 weeks' gestation; further investigation is encouraged.

Abortion, Therapeutic↗
PubMed1993

Serum immunoreactive and bioactive lactogenic hormones in advanced breast cancer patients treated with bromocriptine and octreotide.

6 patients with advanced breast cancer who had failed first and second line endocrine therapies received bromocriptine (1.25-2.5 mg twice daily per os) and octreotide (Sandostatin) via a continuous subcutaneous infusion (200-400 micrograms/24 h) until disease progression. Pre-treatment 24-h profiles of serum lactogenic hormones and their response to standard provocative tests were established and repeated at 2 weeks, and 3 and 6 months (or at tumour progression). Immunoreactive prolactin (ir-PRL), growth hormone (ir-GH) and insulin-like growth factor I (IGF-I) were measured by radioimmunoassay and bioactive lactogenic hormone levels (BLH) were estimated using the Nb2 rat lymphoma cell bioassay. Before treatment all patients showed episodic secretion of ir-PRL, ir-GH and BLH and provocative stimuli resulted in a peak of ir-GH and BLH maximal between 60 and 90 min after injection but no change in ir-PRL. After 2 weeks of treatment, ir-PRL levels were reduced to below the limit of detection in all 6 patients. Peaks of ir-GH and BLH were still apparent, although much reduced. Immunoreactive PRL continued to be profoundly suppressed in 3 of the 4 patients who remained on treatment for 3 to 6 months. Small pulses of ir-GH were still detectable in these patients with which BLH was, again, well correlated. After 2 weeks of treatment, serum IGF-I levels were reduced by 9-54% of the pretreatment values and generally remained suppressed throughout treatment. Clinically, 4 patients did not show disease progression for periods of up to 6 months and side-effects were minimal.

Aged↗
PubMed1993

High dose, dose-intensive chemotherapy with doxorubicin and cyclophosphamide for the treatment of advanced breast cancer.

UNLABELLED: Eighteen patients with advanced breast cancer were commenced on treatment with high dose doxorubicin (100 mg m-2) or doxorubicin (100 mg m-2) and cyclophosphamide (500 mg m-2) at 2 weekly intervals. Three cycles of treatment were planned. rG-CSF was given subcutaneously for 10 days, starting 24 h after each cycle of chemotherapy. Sixteen out of 18 patients responded (89%) of whom six (33%) achieved a complete remission. Twelve (67%) completed the three planned cycles, four (22%) received two cycles and two (11%) received one cycle only. The median time to progression was 5 1/2 months and the median survival was 18 1/2 months. Neutropenia occurred after 89% of courses and 65% of courses were accompanied by a significant (WHO grade III or IV) infection. The duration of neutropenia was short (mean 5.4 days) and mean time to absolute neutrophil count recovery (ANC > 1,000 x 10(6) litre) from the start of treatment was 11 days. Moderate to severe epithelial toxicity (WHO grade 3 or 4) accompanied 43% of courses and was dose limiting. CONCLUSION: High dose, dose intensive chemotherapy has an excellent initial therapeutic effect in advanced breast cancer but does not prolong duration of remission or overall survival beyond that of standard treatment. Although subcutaneous rG-CSF curtailed the expected duration of neutropenia substantially, the overall incidence of neutropenia and of infections requiring intravenous antibiotics was high. Furthermore, almost half of the courses were complicated by moderate to severe oral mucositis and/or mild to moderate palmar and plantar inflammation. The lack of survival benefit and excess toxicity seriously limits the wider application of this regime. It should not be used in place of standard dose palliative chemotherapy for metastatic breast cancer.

Adult↗
PubMed1992

The parathyroid hormone-related protein (PTHrP) gene preferentially utilizes a GC-rich promoter and the PTHrP 1-139 coding pathway in normal human amnion.

Parathyroid hormone-related protein (PTHrP) is an oncofetal protein that is widely expressed in mammalian tissues. The PTHrP gene is a complex with three transcriptional start-sites, two TATA boxes and a GC-rich region, and three predicted polypeptide products, PTHrP 1-141, PTHrP 1-139, and PTHrP 1-173. The originally discovered form of PTHrP, PTHrP 1-141, and the classical TATA box promoters are generally assumed to be the major pathways of PTHrP gene expression. We have used the polymerase chain reaction (PCR) to study PTHrP gene expression in the human amnion. Our studies demonstrate that the GC-rich promoter is preferentially used and that PTHrP 1-139 is the major PTHrP mRNA expressed in human amnion. PTHrP 1-139 lacks the carboxy-terminal arginine and histidine residues of PTHrP 1-141; these two basic amino acids could have significant effects on the biological activity of PTHrP. These preferential pathways for PTHrP gene expression are shared by malignant and normal human tissues.

Amnion↗
PubMed1992

Abundant expression of parathyroid hormone-related protein in human amnion and its association with labor.

In animal models, parathyroid hormone-related protein (PTHrP) increases placental calcium transport and inhibits contraction of uterine smooth muscle. The present studies were undertaken to characterize the expression of PTHrP in human uteroplacental tissues. PTHrP mRNA was identified by Northern analysis as a single species (approximately 1.8 kilobases) in human amnion, chorion, placenta, decidua, and myometrium. The most abundant signal was seen in amnion, where it was 10-400 times that in the other uteroplacental tissues. PTHrP mRNA abundance was decreased in amnion (but not in the other tissues) following the onset of labor (P less than 0.001). PTHrP mRNA in amnion appeared to be translated to a bioactive peptide, as PTHrP bioactivity and immunoreactive PTHrP in amnion correlated closely with PTHrP mRNA content (r = 0.86 and 0.95, respectively; P less than 0.05 and P less than 0.01). Amniotic fluid contained PTHrP, 21 +/- 6 pmol/liter (n = 10) at 16 weeks and 41 +/- 9 pmol/liter (n = 7) at 38 weeks (P = 0.05). These concentrations equaled or exceeded those found in plasma of patients with hypercalcemia secondary to PTHrP. After rupture of the fetal membranes, PTHrP mRNA in amnion was decreased by 78% (P less than 0.0001). This decrease appeared to be specific for PTHrP mRNA, as glyceraldehyde-3-phosphate dehydrogenase mRNA was unchanged following rupture of membranes. Like PTHrP mRNA, PTHrP bioactivity and immunoreactive PTHrP in amnion decreased significantly following rupture of membranes (P less than 0.03 and P less than 0.01, respectively). Since PTHrP is a potent antagonist of uterine muscle contraction, the decrease of PTHrP following rupture of the fetal membranes may play a key role in the onset of labor.

Amnion↗
PubMed1992

Survival of fetuses with 45,X: an instructive case and an hypothesis.

The high (greater than 95%) fetal loss rate of 45,X embryos and fetuses has led to the suggestion that fetal survival with this karyotype requires the presence of mosaicism. However, in many instances, even given a "mild Ullrich-Turner syndrome" phenotype, mosaicism is not detected. In a pregnancy studied for advanced maternal age, CVS cultured cells showed 65% 45,X and 35% 46,X,r(X). After termination, 2 fetal tissues showed 95% 45,X cells. It is suggested that infants with the 45,X karyotype likely had mosaicism for a structurally abnormal X or Y chromosome during embryogenesis, but the abnormal cell line disappeared prior to birth.

Adult↗
PubMed1992

Changes in the extracellular matrix of the normal human breast during the menstrual cycle.

The normal human mammary gland undergoes a well defined sequence of histological changes in both epithelial and stromal compartments during the menstrual cycle. Studies in vitro have suggested that the extracellular matrix surrounding the individual cells plays a central role in modulating a wide variety of cellular events, including proliferation, differentiation and gene expression. We therefore investigated the distribution of a number of extracellular matrix molecules in the normal breast during the menstrual cycle. By use of indirect immunofluorescence, with specific antibodies, we demonstrated that laminin, heparan sulphate proteoglycan, type IV collagen, type V collagen, chondroitin sulphate and fibronectin undergo changes in distribution during the menstrual cycle, whereas collagen types I, III, VI and VII remain unchanged. These changes were most marked in the basement membrane, sub-basement membrane zone and delimiting layer of fibroblasts surrounding the ductules where basement membrane markers such as laminin, heparan sulphate proteoglycan, and type IV and V collagens appear greatly reduced during the mid-cycle period (days 8 to 22). These results suggest that some extracellular matrix molecules may act as mediators in the hormonal control of the mammary gland, whereas others may have a predominantly structural role.

Adenofibroma↗
PubMed1992

Phosphatidic acid and lysophosphatidic acid stimulate receptor-regulated membrane currents in the Xenopus laevis oocyte.

External application of dioleoyl-phosphatidic acid and oleoyl-lysophosphatidic acid stimulated Ca(2+)-dependent chloride currents in voltage-clamped Xenopus laevis oocytes. The responses were observed in oocytes from which follicular cells had been removed, indicating they were intrinsic to the oocyte itself. The lipid-induced Ca(2+)-dependent chloride currents were observed in the absence of extracellular calcium, were blocked by intracellular injection of the calcium chelator, bis(O-aminophenoxy)-ethane N,N,N'N'-tetraacetic acid, and could not be elicited by direct intracellular injection of the active lipids. The thresholds for dose-dependent current responses to dioleoyl-phosphatidic acid (100 nM) and for oleoyl-lysophosphatidic acid (10 nM) indicated that the lipid activities on oocytes were potent. With repeated or prolonged administration of either active lipid, responses exhibited desensitization. These results demonstrate that the Xenopus oocyte expresses endogenous functional responses for the mitogenic lipids phosphatidic acid and lysophosphatidic acid and thus provides a powerful model for characterization of the pharmacology and transduction pathways of these responses.

Animals↗
PubMed1992

Eruptive xanthomas during pregnancy.

A case of eruptive xanthomas during two successive pregnancies is reported. These xanthomas developed in association with marked hypertriglyceridemia; complications included severe pancreatitis and acute respiratory distress syndrome. This patient most likely had combined familial hyperlipidemia which usually causes only a modest elevation in plasma lipid levels. However, with the added stimulus of estrogens during pregnancy, hypertriglyceridemia and secondary complications developed.

Adult↗