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Biomedical subjects

J E Ferguson

Publications and source records attributed to J E Ferguson.

At least 19 recordsLinked to original sources
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↗
PubMed1991

The effects of inositol trisphosphates and inositol tetrakisphosphate on Ca2+ release and Cl- current pattern in the Xenopus laevis oocyte.

We report that Ins(1,3,4,5)P4 releases calcium from intracellular stores of intact Xenopus laevis oocytes, as indicated by two different techniques, Ca2(+)-sensitive microelectrodes and a fura-2 imaging system. Ins(1,3,4,5)P4 releases only 20% as much Ca2+ as the same amount of Ins(1,4,5)P3. This effect is not due to the conversion of the injected Ins(1,3,4,5)P4 to Ins(1,4,5)P3, which is known to release Ca2+, because the amount of [3H]Ins(1,3,4,5)P4 that is converted to Ins(1,4,5)P3 is extremely small, as determined using HPLC. Examination of the different current patterns induced by Ins(1,4,5)P3 and Ins(1,3,4,5)P4, when injected into voltage-clamped oocytes, provided further evidence that the Ins(1,3,4,5)P4 was not being converted back to Ins(1,4,5)P3. We investigated the effects of four compounds, three inositol trisphosphates (Ins(1,4,5)P3, Ins(2,4,5)P3, and Ins(1,3,4)P3), and Ins(1,3,4,5)P4, on Cl- current conductance in order to examine (1) the possible role of Ins(1,3,4,5)P4 in cell activation and (2) the relationships between intracellular Ca2+ and the activation of Cl- currents. Immature stage VI Xenopus laevis oocytes were voltage-clamped and injected with Ins(1,4,5)P3, Ins(2,4,5)P3, and Ins(1,3,4)P3. Ins(1,4,5)P3 and Ins(2,4,5)P3 triggered Ca2(+)-dependent Cl- currents, but Ins(1,3,4)P3 did not trigger currents nor did it release intracellular Ca2+. Ins(2,4,5)P3 was fourfold less effective at inducing the immediate Cl- current pulse than Ins(1,4,5)P3. The Cl- current pattern was quite dependent on the amount of Ins(1,4,5)P3 injected into the oocyte. Low amounts of Ins(1,4,5)P3 triggered only an immediate single Cl- current pulse, whereas large amounts triggered the immediate single pulse, followed by a quiescent period, followed by oscillating Cl- currents. In contrast to the response of Ins(1,4,5)P3, injection of Ins(1,3,4,5)P4 triggered only oscillating Cl- currents whose magnitude, but not pattern, was dependent on the amount injected into the cell. The currents generated by Ins(1,3,4,5)P4 resemble the oscillating Cl- currents triggered by large amounts of Ins(1,4,5)P3 and Ins(2,4,5)P3. Ins(1,3,4,5)P4, unlike Ins(1,4,5)P3 and Ins(2,4,5)P3, rarely caused an immediate Cl- current pulse, but caused an immediate release of calcium. Therefore, we suggest that the oscillating currents are only indirectly dependent on calcium. These [Ca2+]i and conductance measurements suggest that both Ins(1,4,5)P3 and Ins(1,3,4,5)P4 have roles in intracellular Ca2+ regulation.

Animals↗
PubMed1990

The effect of myo-inositol 1,4,5-trisphosphorothioate on Cl- current pattern and intracellular Ca2+ in the Xenopus laevis oocyte.

Microinjection of myo-inositol 1,4,5-trisphosphate into voltage-clamped Xenopus laevis oocytes or the stimulation of the phosphatidylinositol cycle elicits a complex Ca2(+)-dependent Cl- current pattern. Microinjection of myo-inositol 1,3,4,5-tetrakisphosphate causes an immediate release of Ca2+, but elicits a different Cl- current pattern than myo-inositol 1,4,5-trisphosphate. We have studied the effects of myo-inositol 1,4,5-trisphosphorothioate, which can not be converted to myo-inositol 1,3,4,5-tetrakisphosphate. Myo-inositol 1,4,5-trisphosphorothioate caused an immediate release of intracellular Ca2+, as measured by fura-2 imaging. Myo-inositol 1,4,5-trisphosphorothioate generated a Cl- current pattern similar to myo-inositol 1,3,4,5-tetrakisphosphate, not myo-inositol 1,4,5-trisphosphate.

Animals↗
PubMed1990

Transcervical chorionic villus sampling and amniocentesis: a comparison of reliability, culture findings, and fetal outcome.

We evaluated the reliability, culture findings, and fetal outcome after transcervical chorionic villus sampling or amniocentesis in a group of 860 patients. All procedures were performed for the indication of advanced maternal age with consistent procedure and laboratory techniques. Successful procedures were completed in 97.7% (420/430) of patients in the chorionic villus sampling group, compared with 99.5% (428/430) in the amniocentesis group (p less than 0.01). Success was more frequent with only one attempt in the amniocentesis group (427/428) versus 354 of 420 in the chorionic villus sampling group (p less than 0.001). Culture failure was more common after chorionic villus sampling (p less than 0.001). Pregnancy loss rates through 28 weeks' gestation and the entire gestation were not significantly different. The prevalence of preterm delivery did not vary between groups, but birth weights of infants in the chorionic villus sampling group were significantly greater. In summary, the present investigation supports previous findings that chorionic villus sampling is a safe alternative to amniocentesis and is not associated with long-term pregnancy complications.

Abortion, Spontaneous↗
PubMed1990

Diagnosis and management of prenatally detected myelomeningocele: a preliminary report.

Our experience with 23 cases of fetal myelomeningocele provides preliminary information on the outcome of these infants diagnosed in utero and managed by a multidisciplinary team. The mean age of diagnosis was 23.7 weeks (range, 16 to 34 weeks). Mean gestational age at delivery was 36.9 weeks in the 14 patients who elected to continue their pregnancies. None of the 11 infants with lumbosacral or sacral lesions developed significant ventriculomegaly before term. Of the three patients diagnosed with thoracolumbar lesions, two had progression of ventriculomegaly necessitating early delivery at 32 to 34 weeks of gestation. These preliminary findings suggest that a coordinated prenatal and neonatal approach appears to result in a favorable prognosis for infants with myelomeningocele, but that neonatal complications are common, requiring careful monitoring and aggressive management.

Delivery, Obstetric↗
PubMed1990

Activation of protein kinase C triggers premature compaction in the four-cell stage mouse embryo.

During mouse preimplantation development, the cells of the mouse embryo undergo a progressive subcellular reorganization at compaction, which eventually results in the formation of two distinct cell types. We have investigated the effect that activators of the Ca2(+)-phospholipid-dependent protein kinase (PKC) have on mouse compaction. Phorbol ester activation of PKC caused premature compaction of four-cell embryos within a few minutes of addition followed by a prolonged decompaction phase after 1 hr. This response was dose-dependent to concentrations as low as 250 pg/ml. Diacylglycerides also caused compaction; however, it was more sustained than with phorbol esters and was not followed by a phase of decompaction. Inhibition of PKC with sphingosine blocks induced compaction in a dose-dependent manner and also blocks normal compaction of eight-cell embryos. A monoclonal antibody to the cell adhesion molecule, E-cadherin, which mediates mouse embryo compaction, completely blocks compaction induced by these activators of PKC. Indirect immunofluorescence with a monoclonal antibody to E-cadherin indicates that PKC activation causes a rapid shift in the localization of this cell adhesion molecule, which coincides with the observed compaction. These results suggest that PKC plays a role in the initiation of compaction through its effect either directly or indirectly on E-cadherin.

Animals↗
PubMed1990

A comparison of tocolysis with nifedipine or ritodrine: analysis of efficacy and maternal, fetal, and neonatal outcome.

Nifedipine, a dihydropyridone calcium entry blocker, has been used with increasing frequency in the treatment of preterm labor. We studied 66 patients in this prospective, randomized trial to evaluate the efficacy and maternal, fetal, and neonatal outcome associated with tocolysis with nifedipine or ritodrine. Delivery was delayed for 48 hours, 7 days, and until the thirty-sixth week of gestation in 84%, 70%, and 41%, respectively, of patients in the nifedipine group, compared with 72%, 63%, and 52% of patients in the ritodrine group (difference not significant). Maternal side effects were more common and more serious in the group of patients who received ritodrine compared with those who received nifedipine (18 of 38 versus 5 of 38, p less than 0.01); however, fetal and neonatal outcome appeared to be similar when the groups were compared. On the basis of this study, it appears that tocolysis with either nifedipine or ritodrine is equally efficacious; however, maternal side effects are less common with nifedipine treatment. We conclude that nifedipine may have a role in the treatment of preterm labor but suggest further careful evaluation of this agent before it is considered for routine clinical use.

Female↗
PubMed1990

Tenascin distribution in the normal human breast is altered during the menstrual cycle and in carcinoma.

Tenascin is a novel extracellular matrix glycoprotein which appears to have a major role in tissue development. Previous studies have stated that tenascin is absent from the normal human, rat and mouse breast, its distribution being restricted to embryonic and malignant mammary tissues. No previous studies have investigated tenascin distribution as a function of the normal menstrual cycle. Therefore this study addresses the cyclical appearance of tenascin in the normal breast and associated changes in distribution in preinvasive cancer (carcinoma-in-situ) and invasive infiltrating ductal carcinoma. Tenascin is present in the normal human adult mammary gland, principally in the basement membrane, sub-basement-membrane zone and delimiting layer of fibroblasts around the ductules. Both the distribution and quantity of tenascin change during the menstrual cycle. In carcinoma-in-situ (preinvasive cancer) tenascin is present in the attenuated basement membrane/sub-basement-membrane zone around the expanded ductules and in small amounts in the stroma. In infiltrating ductal carcinoma, tenascin is absent from the remnants of the basement membrane and sub-basement-membrane zone but greatly increased in the adjacent intralobular and interlobular stroma. Therefore, if tenascin is used as a basement membrane/sub-basement-membrane marker for distinguishing carcinoma-in-situ from invasive ductal carcinoma, the time of the menstrual cycle is of importance in interpreting the biopsy appearance. This study suggests that the optimal time for biopsy is between weeks 3 and 4 of the cycle, to avoid confusion between the normal low levels of tenascin (due to hormonal status) and those due to microinvasive disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Early diagnosis of spina bifida: the value of cranial ultrasound markers.

Ultrasonography plays an integral part in the prenatal diagnosis of neural tube defects. However, experienced sonographers with careful evaluation are successful in accurately diagnosing spina bifida only 80-90% of the time. This study was conducted to evaluate the accuracy and reliability of certain cranial ultrasound markers--the "lemon sign," cerebellar abnormalities, microcephaly, and ventriculomegaly--in facilitating the diagnosis of spina bifida in patients referred for prenatal diagnosis. Open spina bifida was diagnosed in 24 of 44 fetuses found to have neural tube defects. The lemon sign and cerebellar abnormalities were identified in all 16 fetuses in whom the diagnosis of spina bifida was made between 16-24 weeks' gestation. In four of these fetuses, the lemon sign and cerebellar abnormalities were noted 1-2 weeks before the spinal defect was identified. Microcephaly was present in 69% and ventriculomegaly in 63% of the cases. In the eight cases diagnosed after 24 weeks' gestation, the lemon sign was less reliable, being noted in only 25% of the fetuses. Ventriculomegaly increased in frequency to 75% and cerebellar abnormalities and microcephaly were present in all. Our findings indicate that these cranial ultrasound markers are extremely reliable for the early diagnosis of spina bifida; their identification should alert ultrasonographers at all skill levels to the possibility of open spina bifida.

Cerebral Ventricles↗
PubMed1989

The role of ultrasonography and amniocentesis in the evaluation of pregnancies at risk for neural tube defects.

To assess the relative efficacy of amniocentesis versus targeted (detailed) ultrasonography, 225 patients referred because of an elevated maternal serum alpha-fetoprotein level (79.6%) or a family history of neural tube defect (20.4%) were evaluated. Ultrasonographic examination alone detected all 26 fetal abnormalities (11 cases of anencephaly, 10 cases of open spina bifida, and five other anomalies). Twenty-eight patients declined amniocentesis; all had normal pregnancy outcomes. Of the 167 patients with apparently normal fetal anatomy by sonography, seven had elevated alpha-fetoprotein levels but no acetylcholinesterase in the amniotic fluid. Six of these pregnancies resulted in normal infants; one infant had congenital nephrosis. The remaining 160 patients had normal sonograms with normal amniotic fluid alpha-fetoprotein levels and no fetal malformations at delivery. Although these results suggest that targeted ultrasonography by experienced personnel is a reasonable alternative to amniocentesis in evaluations for neural tube defects, the availability, cost-effectiveness, and diagnostic accuracy of this approach must be well documented in large prospective studies.

Acetylcholinesterase↗