Search PubMed⌕ Search

Biomedical subjects

J C Murray

Publications and source records attributed to J C Murray.

At least 199 records · Page 11Linked to original sources
PubMed1991

Characterization of the calcitonin/CGRP gene in Williams syndrome.

We have investigated the possibility of mutations in the calcitonin/calcitonin gene related peptide (CGRP) gene in children with Williams syndrome. Involvement of the calcitonin/CGRP gene in Williams syndrome is postulated on the basis that Williams syndrome children often have infantile hypercalcemia and deficient expression of calcitonin, a hormone that lowers serum calcium levels. To test the hypothesis that mutations in the calcitonin/CGRP gene might be responsible for the reduced calcitonin levels, we examined the calcitonin/CGRP gene structure in Williams syndrome children. Analysis of white blood cell DNA by Southern blot hybridizations in 5 individuals did not show any detectable large deletions or rearrangements in the calcitonin/CGRP gene locus. The possibility of small deletions or point mutations within the exon encoding the mature calcitonin hormone is unlikely based on ribonuclease protection assays with patient DNA amplified by the polymerase chain reaction (PCR) technique. These findings suggest that the calcitonin deficiency might be due either to mutations elsewhere in the gene or to defects in the cellular machinery needed for calcitonin synthesis and/or secretion.

Adolescent↗
PubMed1991

Flavone acetic acid potentiates the induction of endothelial procoagulant activity by tumour necrosis factor.

Treatment of human umbilical vein endothelial cells with flavone acetic acid (FAA) at 800 micrograms/ml for 4 h resulted in a 3-11-fold increase in procoagulant activity. This increase was due to enhanced tissue factor expression on the endothelial cell surface, as evidenced by the blocking of the enhanced clotting with antibody to tissue factor, by substitution of normal with factor VII deficient plasma, or by simultaneous treatment of the endothelial cells with cycloheximide or actinomycin D. FAA was not toxic to endothelial cell at concentrations up to 1.6 mg/ml over 4 h. Combined treatment with FAA and tumour necrosis factor alpha (TNF-alpha) (100 pg/ml) produced a 675-fold (range 160-1980) increase in tissue factor activity, compared to 5-fold and 50-fold increases for the individual agents respectively. Northern blotting of total RNA from cells treated with the combination of agents or either agent alone, followed by probing with a cDNA to human tissue factor demonstrated a synergistic increase in tissue factor mRNA after combination treatment. In vivo, the combination of FAA and TNF-alpha could be shown to induce greater growth delay in two murine tumours than would be predicted on the basis of the activity of either agent alone.

Animals↗
PubMed1991

Genetic and physical mapping around the properdin P gene.

A CA repeat has been found on the human X chromosome within 16 kb of the gene encoding properdin P factor (PFC) and has been shown to be a highly informative marker. Two more polymorphic CA repeats were found in a cosmid containing DXS228. The CA repeats, and other markers from proximal Xp, were mapped genetically in CEPH families and the likely order of markers was established as Xpter-(DXS7, MAO-A, DXS228)-(PFC, DXS426)-(TIMP, OATL1)-DXS255-Xcen. This places PFC in the region Xp11.3-Xp11.23, thus refining previous in situ hybridization data. Two yeast artificial chromosomes (YACs) (440 and 390 kb) contain both PFC and DXS426, and one of them (440 kb) also contains TIMP. This confirms the genetic order TIMP-(PFC, DXS426). PFC and TIMP are located on the same 100-kb SalI/PvuI fragment of the 440-kb YAC. Given the genetic orientation of TIMP and (PFC, DXS426), this YAC can now serve as a starting point for directional walking toward disease genes located in Xp11.3-Xp11.2 such as retinitis pigmentosa (RP2) and Wiskott-Aldrich syndrome.

Base Sequence↗
PubMed1991

The CEPH consortium linkage map of human chromosome 1.

This paper describes the Centre d'Etude du Polymorphisme Humain (CEPH) consortium linkage map of human chromosome 1. The map contains 101 loci defined by genotypes generated from CEPH family DNAs with 146 different contributions from 11 laboratories. A total of 58 loci are uniquely placed on the map with likelihood support of at least 1000:1. The map extends from loci in the terminal bands of both chromosome arms (locus D1Z2 in 1p36.3 and D1S68 in 1q44) and is anchored at the centromere by the D1Z5 alpha-satellite polymorphism. With the exception of a single locus, the remaining loci are arrayed on the fixed map in short intervals and their possible locations are indicated. Multipoint linkage analyses provided estimates that the male, female, and sex-averaged maps extend for 308, 478, and 390 cM, respectively. The sex-averaged map contains only four intervals greater than 15 cM, and the mean genetic distance between the 58 uniquely placed loci is 6.7 cM.

Chromosome Mapping↗
PubMed1991

Anticoagulant treatment does not affect the action of flavone acetic acid in tumour-bearing mice.

Flavone acetic acid (FAA) is a novel antitumour agent that has a profound effect on the vasculature in murine tumour models. Previously we have shown that FAA induces a coagulopathy and thrombocytopaenia in tumour-bearing mice, and the purpose of the present study was to determine the significance of the FAA-induced intravascular coagulation in the antitumour action of FAA. Several anticoagulant agents were tested for their effectiveness in altering ex vivo coagulation of murine plasma; heparin and ancrod were found to be most effective. These agents were administered to tumour-bearing mice prior to FAA and TNF treatment with little effect on the induced regrowth delay. However: the FAA-induced consumption of platelets in tumour-bearing mice was not blocked by anticoagulant treatment. These data suggest that platelet consumption occurs independently of the normal coagulation pathway, and further that fibrin deposition may not be a major factor in the antitumour action of FAA.

Adenocarcinoma↗
PubMed1991

Determination of X-ray-induced damage to the murine colon using tissue compliance measurements.

A proctometroscope has been developed to measure the mechanical functioning of the colon in a murine model. A balloon-tipped probe is inserted into the colorectal region of anaesthetized mice and inflated hydraulically, at a constant rate, by a motor-driven syringe. Balloon pressure and volume are monitored, processed and plotted on a X-Y/t recorder. The balloon is inserted within the irradiated area, such that the centre of the balloon is 1 cm proximal to the anus, and inflated up to either a maximum volume of 100 microliters or a maximum pressure of 100 cmH2O, depending on which occurs first. Compliance (delta V/delta P) of the colon was measured at various intervals following X-irradiation, a dose-dependent decrease being observed at 24 weeks. This decrease was progressive with time out to 72 weeks postirradiation. The compliance measured, in both control and irradiated groups, was not dependent on the inflation rate used to make the determination, and no iatrogenic effects have been detected after repeated probing during a long-term study. The use of different anaesthetic agents was also investigated, no significant difference between the compliance of mice anaesthetized with the different agents being detected. Use of this technique provides fully quantitative data on the function of the colon following radiation injury, and provides an alternative to other physiological assays. The technique is non-destructive, rapid, easy to use and non-invasive to the tissue, thus the onset and progression of damage can be followed in each mouse over long postirradiation periods.

Animals↗
PubMed1991

Chromosomal localization of the human gene for annexin V (placental anticoagulant protein I) to 4q26----q28.

Annexin V is a member of a new family of calcium-dependent phospholipid-binding proteins. It has been previously isolated as placental anticoagulant protein I, inhibitor of blood coagulation, vascular anticoagulant-alpha, endonexin II, lipocortin V, placental protein 4, and anchorin CII. The human gene encoding annexin V (ANX5) was localized to 4q26----q28 by in situ hybridization with a cDNA probe and polymerase chain-reaction (PCR) analysis of a human x hamster hybrid cell panel. The regional localization to 4q26----q28 was supported by Southern-blot analysis of a human cell line with a deletion in 4q23----q27. This localization overlaps but differs slightly from the previous assignment of ANX5 to 4q28----q32. Digestion with PvuII and TaqI identified polymorphisms at the ANX5 locus; the PvuII polymorphism could also be detected by PCR analysis.

Animals↗
PubMed1990

A polypeptide factor produced by fibrosarcoma cells that induces endothelial tissue factor and enhances the procoagulant response to tumor necrosis factor/cachectin.

Intravascular clot formation, localized to the neoplasm, is an early component of the vascular response to tumor necrosis factor (TNF)/cachectin. Fibrin is closely associated with the endothelial cell surface, and multiple microthromboses lead to reduced blood flow in the tumor. We have identified a tumor-derived mediator which enhances endothelial procoagulant activity and the cellular response to TNF using cultured cells derived from a murine methylcholanthrene A (meth A)-induced fibrosarcoma as a model system. A heat-stable protease K-sensitive polypeptide, Mr approximately 44,000 on nonreduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Mr approximately 56,000 reduced), was purified approximately 500,000-fold from serum-free culture supernatants of meth A cells by sequential Q-Sepharose, Mono S, reversed phase, and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Based on immunologic criteria, biologic activity, and other molecular properties, meth A factor appears to be distinct from other cytokines and growth factors. Purified meth A factor induced transcription of the tissue factor gene and expression of procoagulant activity by cultured human endothelium (half-maximal effect for the latter at approximately 6-8 pM). Furthermore, co-incubation of endothelium with meth A factor together with TNF enhanced induction of tissue factor in a more than additive manner. These data indicate that certain tumors elaborate an apparently unique molecule which can alter hemostatic properties of the vessel wall, potentially modulating reactivity of the tumor vasculature to host response mediators.

Animals↗
PubMed1990

Determination of collagen and protein turnover by high-performance liquid chromatography.

A high-performance liquid chromatographic method is described for the determination of tissue collagen and protein synthesis rates in vivo, together with an index of collagen degradation. The technique utilises post-column reaction with 7-chloro-4-nitrobenzofurazan (NBDCl), which shows higher reactivity towards the secondary amino acids, proline and hydroxyproline, and also exploits differences in absorbance and fluorescence spectra to avoid interference by primary amino acids, including cysteine which reacts rapidly with NBDCl. The relative benefits of using fluorescence or absorbance detection are discussed. A detailed description is given of the steps involved in sample preparation and data for five normal tissues in the mouse are presented using fluorescence detection.

4-Chloro-7-nitrobenzofurazan↗
PubMed1990

A detailed multipoint gene map of chromosome 1q.

Utilizing genotyping data for 23 markers, we have constructed a 21-locus multipoint genetic map of the long arm of chromosome 1. Five new RFLPs are reported. The map integrates anonymous loci from previous primary linkage maps and incorporates markers for 10 coding sequences. These markers form a continuous linkage group of 85 cM in males and 141 cM in females. The map was constructed employing the LINKAGE and CRIMAP computational methodologies via a stepwise algorithm.

Algorithms↗
PubMed1990

Pregnancy and the skin.

Physiologic skin changes and certain dermatoses characteristically occur during pregnancy. Any cutaneous change is rarely ignored, as the patient is concerned about her own and her fetus's well-being. Physiologic changes include pigmentation, vascular growth, varicosities, telogen effluvium, and striae. These changes are reviewed along with other dermatoses usually associated with pregnancy. Some dermatoses of pregnancy are infrequently reported, as an understanding of possible etiologies remains limited for the varied dermatoses.

Female↗
PubMed1990

Linkage of an autosomal dominant clefting syndrome (Van der Woude) to loci on chromosome Iq.

Van der Woude syndrome (VWS) is an autosomal dominant disorder in which affected individuals have one or more of the following manifestations: cleft lip, cleft palate, hypodontia, or paramedian lower-lip pits. VWS is a well-characterized example of a single-gene abnormality that disturbs normal craniofacial morphogenesis. As a first step in identifying genes involved in human development, we used a candidate-gene-and-region approach to look for a linkage to VWS. Six families with 3 or more generations of affected individuals were studied. Evidence for linkage (theta = 0.02, lod score = 9.09) was found between the renin (REN) gene on 1q and VWS. Other linked loci included CR1, D1S58, and D1S53. The genes for laminin B2 (LAMB2), a basement-membrane protein, and for decay-accelerating factor (DAF) were studied as possible candidate genes on 1q. Recombinants between VWS and both LAMB2 and DAF excluded these genes from a causal role in the etiology of VWS for the families studied in this report. Multipoint linkage analysis indicated that the VWS locus was flanked by REN and D1S65 at a lod score of 10.83. This tight linkage with renin and other nearby loci provides a first step in identifying the molecular abnormality underlying this disturbance of human development.

Chromosomes, Human, Pair 1↗