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G R Sutherland

Publications and source records attributed to G R Sutherland.

At least 469 records · Page 26Linked to original sources
PubMed1988

Structure and chromosomal localization of the human renal kallikrein gene.

Glandular kallikreins are a family of proteases encoded by a variable number of genes in different mammalian species. In all species examined, however, one particular kallikrein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. This kallikrein is found in the kidney, pancreas, and salivary gland, showing a unique pattern of tissue-specific expression relative to other members of the family. We have isolated a genomic clone carrying the human renal kallikrein gene and compared the nucleotide sequence of its promoter region with those of the mouse renal kallikrein gene and another mouse kallikrein gene expressed in a distinct cell type. We find four sequence elements conserved between renal kallikrein genes from the two species. We have also shown that the human gene is localized to 19q13, a position analogous to that of the kallikrein gene family on mouse chromosome 7.

Amino Acid Sequence↗
PubMed1988

Localization of the human G-CSF gene to the region of a breakpoint in the translocation typical of acute promyelocytic leukemia.

The colony-stimulating factors regulate growth, differentiation, and function of blood cells. The effect of granulocyte colony-stimulating factor (G-CSF) on myeloid leukemias is unique among colony-stimulating factors in driving the leukemic cells from a self-renewing malignant state to a mature differentiated phenotype with the concomitant loss of tumorigenicity. This property of G-CSF has led to suggestions that its absence is responsible for lack of differentiation of leukemic cells and that the therapeutic administration of G-CSF could reverse this defect and result in a cure for leukemia. Here we show that the gene coding for human G-CSF is localized to chromosome 17, bands q11.2-21. The translocation of the long arm of chromosome 17 at q12-21 to chromosome 15 is a specific abnormality occurring in a high proportion of, if not all, patients with acute promyelocytic leukemia, a disease characterized by undifferentiated myeloid cells and a dismal prognosis. Abnormalities of the regulation of a specific differentiation factor gene mediated by a specific chromosomal rearrangement may be directly implicated in the pathogenesis of human leukemia.

Chromosome Mapping↗
PubMed1988

Further localization of ETS1 indicates that the chromosomal rearrangement in Ewing sarcoma does not occur at fra(11)(q23).

A genomic probe homologous to 5.4 kb of the c-ets-1 gene was hybridized in situ to chromosomes expressing fra(11)(q23). This probe hybridized distal to the fragile site, which is just distal to the midpoint of band 11q23.3. This result localizes ETS1 from the FRA11B locus to 11q24. The result also distinguishes the FRA11B locus from the site of translocation at 11q23-q24 in the Ewing sarcoma- and peripheral neuroepithelioma-specific t(11;22), indicating that the chromosomes of a previously reported patient heterozygous for fra(11)(q23) did not rearrange at this fragile site to give rise to Ewing sarcoma. This adds to the mounting evidence against individuals with fragile sites being predisposed to developing cancer.

Chromosome Banding↗
PubMed1988

Interleukin 4 is at 5q31 and interleukin 6 is at 7p15.

DNA probes to the human interleukin 4 (IL4) and interleukin 6 (IL6) genes have been used for in situ hybridization to normal human chromosomes and Southern blot analysis of a series of mouse-human hybrid cell lines. IL4 maps to 5q31, the same location as IL5 and other haemopoietic growth factor genes. IL6 maps to 7p15. The significance of these locations is discussed.

Chromosome Mapping↗
PubMed1988

Restriction fragment length polymorphisms detected by anonymous DNA probes mapped to defined intervals of human chromosome 16.

Three anonymous DNA probes ACH207, ACH224, and ACH202, isolated from a flow-purified chromosome 16 library and mapped to defined intervals of human chromosome 16, detected restriction fragment length polymorphisms (RFLPs). The RFLPs were of simple two allele types. The ACH207 (D16S4) probe detected a TaqI and an MspI RFLP with polymorphism information content (PIC) values of 0.30 and 0.27; the ACH224 (D16S5) probe detected an RsaI RFLP, PIC value of 0.34; and the ACH202 (D16S4) probe detected an XbaI RFLP, PIC value of 0.22.

Alleles↗
PubMed1988

No statistical association between common fragile sites and nonrandom chromosome breakpoints in cancer cells.

Fragile sites and nonrandom chromosome breakpoints in cancer cells are not distributed at random within the genome, but occur mainly in the light G-bands. If this nonrandom distribution is taken into account and a statistical analysis for the association of these two phenomena within the same chromosome band is carried out, based on the 400-band karyotype, no significant association is found between the common fragile sites and cancer breakpoints although there remains an association between the rare fragile sites and cancer breakpoints. These results, along with other chromosome mapping evidence that rare fragile sites are not at the breakpoint in some cancer chromosome rearrangements, cast serious doubt on any role for fragile sites in oncogenesis.

Chromosome Banding↗
PubMed1988

Translocation breakpoint in t(11;14) in B-cell leukemia is not at the rare fragile site at 11q13.3.

The cloned breakpoint at 11q13.3 of the t(11;14)(q13.3;q32.3) in a B-cell lymphocytic leukemia (B-CLL) was used to analyze DNA from individuals with and without the rare folate-sensitive fragile site at 11q13.3. On Southern blots there were no discernible differences. Subclones of the ends of the leukemia breakpoint clone were prepared and used for in situ hybridization to chromosomes expressing fra(11)(q13.3). Both subclones hybridized distal to the fragile site. These experiments indicate that the breakpoints at 11q13.3 in B-CLL (and in a B-cell lymphoma) are not at the fragile site at 11q13.3.

B-Lymphocytes↗
PubMed1988

Improved diagnosis and characterization of left ventricular pseudoaneurysm by Doppler color flow imaging.

Three patients with a left ventricular pseudoaneurysm are presented. Doppler color flow imaging helped to establish the diagnosis and was able to show additional blood flow abnormalities. The guided continuous wave Doppler interrogation of the shunting blood flow through the communication between the pseudoaneurysm and the left ventricle allowed the identification of a specific diagnostic flow pattern. Doppler color flow imaging offers advantages in patients with equivocal two-dimensional echocardiographic findings for elucidating confusing clinical findings and demonstrating additional and unsuspected flow abnormalities.

Aged↗
PubMed1988

Fine mapping of gene probes and anonymous DNA fragments to the long arm of chromosome 16.

The fragile site, FRA16B, at 16q22.100 and four different translocations with breakpoints at 16q22.102, 16q22.105, 16q22.108, and 16q22.3 were used to locate and order DNA probes. This was achieved by Southern analysis of a somatic cell hybrid panel containing portions of chromosome 16 and by in situ hybridization. The anonymous DNA fragments D16S6, D16S10, and D16S11 were proximal to FRA16B and located at 16q13----q22.100. D16S4 and LCAT were located at 16q22.100----q22.102. TAT and HP were located at 16q22.105----q22.108. CTRB was located distal to 16q22.105 and therefore is in the distal half of 16q22. The order of markers in this region was determined as centromere-D16S6, D16S11, D16S10, MT-FRA16B-D16S4, LCAT-HP,TAT,CTRB-APRT- telomere. Linkage studies to determine map distances between the closest markers flanking the fragile site are now in progress.

Animals↗
PubMed1988

Human prostate-specific antigen (APS) is a member of the glandular kallikrein gene family at 19q13.

The amino acid sequence of human prostate-specific antigen (APS) suggests that it is a member of the glandular kallikrein subfamily of serine proteases. In the mouse, the kallikrein-like family is localized in a single locus on chromosome 7, while other serine proteases are distributed over a variety of different chromosomes. To investigate the physical relationship between the human kallikrein genes, we have used in situ hybridization and Southern analysis of a human x mouse somatic cell hybrid panel to map the APS gene to 19q13, concordant with the renal kallikrein KLK1 gene. This finding indicates that APS is a member of a human kallikrein-like gene family with analogous organization to that of the mouse.

Antigens, Neoplasm↗
PubMed1988

Platelet aggregation within cerebral arteriovenous malformations.

Turbulence within cerebral arteriovenous malformations (AVM's) may lead to endothelial disruption, platelet aggregation, and thrombus formation. This hypothesis would account for many of the pathological features in AVM's, including intimal hyperplasia and arterial thrombosis with or without organization. In this study, a dual-isotope method employing indium-111-labeled platelets and technetium-99m-labeled red blood cells was used to evaluate in vivo platelet aggregation in 20 patients with AVM's. The use of two isotopes allows subtraction of the blood-pool platelets and calculation of the ratio of the indium deposited:the indium in the blood pool (In(D)/In(BP)). After a 24-hour incubation period, eight of the 20 patients demonstrated platelet aggregation in their AVM's with a mean In(D)/In(BP) ration of 0.71 +/- 0.36 (+/- standard deviation). Seven of these AVM's were available for pathological study and all of them demonstrated evidence of arterial thrombosis of variable age. In the remaining 12 patients, the In(D)/In(BP) ratio was not significantly elevated (mean 0.02 +/- 0.13), indicating the absence of active platelet aggregation during this short interval of study. Five of these AVM's were pathologically examined, four of which showed evidence of arterial occlusion. It is concluded that platelet aggregation is a common occurrence in cerebral AVM's and may account for the dynamic histopathology often seen in these lesions.

Adult↗
PubMed1988

Application of DNA probes to carrier detection and prenatal diagnosis of Duchenne (and Becker) muscular dystrophy.

Thirty-four Duchenne and Becker muscular dystrophy families were initially ascertained from South Australia. These have been tested systematically with the DNA probes XJ1.1 and pERT87-15. DNA results from 21 informative families have been combined with results of CK testing. Pedigree analysis was carried out using the computer program LINKAGE to provide risk figures to potential female carriers. This simple approach separated potential carriers into low or high risk classes (familial cases) or low or moderate risk classes (isolated cases). No prenatal diagnoses were carried out. The detection of deletions in two probands out of 34 makes possible definitive prenatal diagnosis in those families. For the remaining families, prenatal diagnosis could only be offered in terms of a probability statement after linkage analysis. Risk figures presented from hypothetical pedigrees demonstrated that prenatal diagnosis by linkage usually provided reasonable reliability only where informative flanking markers are used.

Child↗