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Biomedical subjects

G Bates

Publications and source records attributed to G Bates.

At least 55 records · Page 3Linked to original sources

The role of bacterial infection of the maxillary sinus in nasal polyps.

Fifty-two adult patients with nasal polyps were studied. All patients had preoperative sinus radiographs which were coded on the degree of mucosal thickening and these were compared with the results of irrigation of the maxillary sinuses. All irrigations were sent for culture and microscopy for pus cells. Pus cells and bacteria were found in only 16 of 104 wash-outs. It was concluded that the disease results in stasis of secretions and secondary maxillary sinusitis.

Bacterial Infections↗

A long-range restriction map encompassing the cystic fibrosis locus and its closely linked genetic markers.

The cystic fibrosis (CF) locus has been localized to the long arm of chromosome 7 by linkage analysis, and the genetic relationship between CF and the probes J3.11, met, and 7C22 has been extensively studied. To extend this genetic analysis to higher resolution, to provide information on physical distances underlying the genetic relationships, and to set limits to the position of the cystic fibrosis mutation, we have constructed a partial restriction map covering approximately 5 Mb that defines the physical relationship between these and the more recently isolated markers CS.7, XV-2c, Lcn2, and C2/5. Allelic association indicates that CS.7 and XV-2c are close to the CF locus, and an expressed sequence from this region has been described as a candidate gene for this mutation (X. Estivill et al., 1987, Nature (London) 326: 840-845). Using pulsed-field gel electrophoresis we have determined the physical order of these markers to be cen-7C22-Lcn2-met-C2/5-XV-2c-CS.7-J3.11-tel and have localized the CF mutation to an interval of less than 1500 kb. A (not unexpected) disproportionality was observed between the currently best estimates of genetic and physical distances, with the interval J3.11-met showing an approximately fourfold higher frequency of recombination than the met-7C22 interval.

Chromosome Mapping↗

Biochemical and genetic exclusion of calmodulin as the site of the basic defect in cystic fibrosis.

Recent physiological studies have shown a defective beta-adrenergic regulation of chloride transport and protein secretion in tissues affected by cystic fibrosis. The exact biochemical nature of this abnormality is unknown, but an intracellular second messenger may be involved. We have tested the hypothesis that calmodulin is the site of the basic defect in CF using biochemical and molecular genetic techniques. We report here that there is no gross structural abnormality in the calmodulin protein from CF submandibular glands, and that although there are at least three distinct sequences that cross-hybridise with a calmodulin cDNA probe in the human genome, none of these can be the locus of CF. A polymorphism at the locus of a calmodulin cross-hybridising sequence at human chromosome 7p2 is described.

Alleles↗

The application of molecular genetics to the study of the basic defect causing cystic fibrosis.

The first linkage to CF was demonstrated to the enzyme paroxonase, a classical protein polymorphism, by the Copenhagen group. This was followed quickly by six cloned DNA sequences: pJ3.11, 7C22, COL1A2 and TCRB (St. Mary's), 917 (Toronto) and met (Salt Lake City). Both pJ3.11 and met are very close genetically to the CF mutation, and can be used for carrier detection and antenatal diagnosis in many informative families where there is a CF child. There is no evidence for heterogeneity of the CF locus. The collection of markers surrounding the CF locus is now sufficient to permit attempts to be made to isolate the defective gene using a combination of chromosome-mediated gene transfer, pulse field gel electrophoresis, NotI junction libraries, cosmid mapping and chromosome walking techniques.

Chromosome Mapping↗

Isolation of a further anonymous informative DNA sequence from chromosome seven closely linked to cystic fibrosis.

A library prepared from flow-sorted chromosomes was used to isolate single-copy sequences from chromosome seven. One such sequence 7C22 has been shown to be polymorphic for an EcoRI restriction site and to be informative for the study of CF in approximately 35% of matings. The segregation of the 7C22 alleles was followed through nineteen informative families with more than one child affected by cystic fibrosis. We report that the locus for 7C22 is linked to the locus for cystic fibrosis at a recombination fraction of 0.045. This marker will prove useful in improving the accuracy and informativeness of prenatal diagnosis and in constructing a fine genetic map around the cystic fibrosis gene.

Chromosomes, Human, 6-12 and X↗

Further data supporting linkage between cystic fibrosis and the met oncogene and haplotype analysis with met and pJ3.11.

The linkage of cystic fibrosis (CF) and the polymorphic DNA markers pJ3.11, met, 7C22, DOCR1-917, COL1A2, and TCRB have jointly localized the mutation causing CF to chromosome 7q2.1-3.1. We report further linkage data with two polymorphic markers at the met oncogene locus, pmetH and pmetD, which supports the tight linkage found by White et al. between CF and met. One family shows evidence for meiotic recombination between CF and met. Analysis of haplotypes in CF pedigrees collected for linkage studies combined with data from single affected families requesting prenatal diagnosis (Farrall et al., Lancet i:1402-1404, 1986) shows CF and met to be in linkage equilibrium in our population while pJ3.11-CF haplotypes show a deviation from the equilibrium frequencies.

Cystic Fibrosis↗

Ultrastructural alterations in glycosaminoglycans of dog femoral condylar cartilage after surgical division of an anterior cruciate ligament: a study with cupromeronic blue in a critical electrolyte concentration technique.

The cationic dye, cupromeronic blue, has been used in a critical electrolyte concentration technique to analyse the ultrastructural changes in cartilage matrix glycosaminoglycans which occur in the dog anterior cruciate ligament division model of osteoarthrosis. Amorphous material appearing at the articular surface of cartilage from the stifle joints of animals subjected to open surgical division of the anterior cruciate ligament has been shown not to comprise glycosaminoglycan. The nature of this material is unknown, but it appears to replace the surface lamina of normal cartilage. It may therefore affect the mechanical properties of the superficial cartilage. The pericellular matrix around single chondrocytes or separating pairs of chondrocytes becomes enriched with sulphated glycosaminoglycan as a response to ligament section. This material is thought to be newly synthesised and secreted and reflects the increased cellular activity resulting from surgically induced canine joint disease.

Animals↗

Mapping DNA sequences in a human X-chromosome deletion which extends across the region of the Duchenne muscular dystrophy mutation.

A somatic cell hybrid has been constructed and characterized using fibroblasts from a phenotypically normal woman who possesses an X chromosome with an interstitial deletion of the short arm. High-resolution banding indicates that the deleted segment is either Xp22.13-p11.4 or Xp22.11-p11.23. Southern blot hybridization to previously mapped DNA sequences confirms that the missing segment of the X chromosome is a deletion and not an interstitial translocation and supports the cytogenetic interpretation that the deletion extends proximal of Xp11.3 and therefore probably comprises Xp22.11-p11.23. Three further DNA sequences have been localized to the region of the deleted segment. The following order has been assigned to the seven probes used: Xpter-RC8-pXUT22-(OA1,C7,M2C)-L1.28-RD6 -Xcen.

Animals↗

Serum alpha fetoprotein heterogeneity as a means of differentiating between primary hepatocellular carcinoma and hepatic secondaries.

The concanavalin A binding characteristics of serum alpha-fetoprotein (AFP) were investigated in patients with primary hepatocellular carcinoma and hepatic secondaries using affinity column chromatography and radioimmunoassay. The primary hepatocellular carcinoma (n = 21) was associated with a median concanavalin A non-reactive AFP fraction of 7.4% (range 1.6 - 18.8) while the hepatic secondaries (n = 8) had a median concanavalin A non-reactive AFP fraction of 50.7% (range 26.6 - 91.7). A simple diagnostic test for differentiating between the two groups of patients is proposed.

Adolescent↗

Maternal zinc status: a determination of central nervous system malformation.

Maternal serum zinc concentrations were estimated during 244 normal pregnancies and 15 abnormal pregnancies. The serum zinc concentrations were lower in the anencephalic pregnancies than in the normal control subjects. The serum zinc levels in women whose pregnancies terminated in a spontaneous abortion were normal. There was no variation of serum zinc level with gestational age between 15 to 18 weeks in normal pregnancies.

Abortion, Spontaneous↗

Serum ferritin as a third marker in germ cell tumours.

Serial measurements of serum ferritin have been assessed as an additional marker in a study of 12 patients with germ cell tumours. The standard markers, serum AFP and beta HCG, were also assessed serially. During treatment elevated levels of serum ferritin were detected in 10 patients, elevated AFP in 10 patients and elevated beta HCG in 6 patients. A poor prognosis was associated with persistently raised serum ferritin and either, or both, elevated AFP and beta HCG levels. Decreasing levels of serum ferritin indicated favourable response to treatment; rising values were associated with recurrence or dissemination of tumour. Even if serum ferritin cannot be classed specifically as a tumour product, it may be useful in the early detection of residual or recurrent tumour.

Adolescent↗

Detection and measurement of fetomaternal haemorrhage: serum alpha-fetoprotein and the Kleihauer technique.

A raised maternal serum alpha-fetoprotein concentration was taken as an indicator of fetomaternal haemorrhage due to amniocentesis and was used to calculate the volume of the fetal bleed. The alpha-fetoprotein concentration seemed to be a more sensitive and reliable indicator than the established Kleihauer technique and may have further applications in antenatal testing.

Amniocentesis↗