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R W Elliott

Publications and source records attributed to R W Elliott.

At least 73 records · Page 4Linked to original sources

DNA sequence variation within the beta-glucuronidase gene complex among inbred strains of mice.

Tightly linked to the gene that encodes murine beta-glucuronidase (GUS) are three GUS-specific regulatory elements. Together, these elements define the GUS gene complex. Specific alleles of each regulatory element are associated with a specific GUS structural allele. These associations define the three common forms (haplotypes) of the GUS gene complex, designated A, B, and H. As an initial step in defining the DNA determinants of each regulatory element and to develop DNA markers for the common haplotypes, we have identified several DNA variants by blot hybridization analysis of restricted genomic DNA using GUS-specific cDNA probes. Of 30 tested restriction endonucleases, 24 reveal DNA polymorphisms that distinguish B- and H-haplotype DNA from that of the A haplotype. Of these 24, 18 uncover a restriction fragment length polymorphism in which the polymorphic fragment of A-haplotype DNA is 200-300 bp larger than the corresponding fragment of B- or H-haplotype DNA. DNA sequence analysis of this polymorphic region reveals the presence of a short, interspersed repetitive element of the B2 family within A-haplotype DNA which is absent in DNAs of B- or H-haplotype mice. None of the DNA variations revealed by these analyses can be associated at this time with variation in the regulatory or structural properties of GUS among the common haplotypes. Nevertheless, they do provide useful haplotype-specific markers within the GUS gene complex which are of critical importance for DNA transfer experiments in transgenic mice and in cultured cells.

Animals↗

Renal replacement therapy in patients aged over 60 years.

The availability of dialysis for patients with end-stage renal failure in the United Kingdom has lagged behind that in most of the rest of Europe and USA, although there has been considerable improvement over recent years. Concern about prognosis and quality of life on renal replacement therapy, together with shortage of facilities has meant that some elderly people have been denied treatment. A retrospective study of all patients commencing renal replacement therapy in Newcastle between 1974 and 1985 was performed. The five year survival of patients aged more than 60 years at the start of treatment (n = 122) was 53%, compared with 68% for a cohort of individuals aged less than 60 years (n = 632). A questionnaire sent to the 62 elderly patients surviving at the end of the follow-up period revealed that most were married, independent, active and lived in their own home. They were not lonely, generally enjoyed life and were happy with their mode of renal replacement therapy. These results show that elderly patients make good dialysis candidates and they should not be denied treatment on the basis of age alone. Greater funding of renal services is necessary to accommodate these patients.

Age Factors↗

Developmental and transformation-sensitive expression of the Sparc gene on mouse chromosome 11.

SPARC is a Mr 43,000 secreted, acidic, cysteine-rich glycoprotein homologous to 43K bovine endothelial 'culture shock' protein. We show here that it is encoded by a single gene localized to the central region of mouse chromosome 11. During development SPARC mRNA is expressed at higher levels in all the extra-embryonic tissues than in the fetus. Highest levels are found in the parietal endoderm, while visceral endoderm has approximately 6-fold less. This differential expression is also seen in F9 teratocarcinoma cells treated with retinoic acid under conditions in which they give rise to either parietal or visceral endoderm. The 20-fold increase seen during differentiation into parietal endoderm is due, at least in part, to an increase in gene transcription. We also report SPARC expression in a variety of adult tissues and cultured cells, and present evidence that a decrease accompanies the transformation of fibroblast cell lines.

Animals↗

Nonhomologous pairing in mice heterozygous for a t haplotype can produce recombinant chromosomes with duplications and deletions.

We have investigated the structure and properties of a chromosomal product recovered from a rare recombination event between a t haplotype and a wild-type form of mouse chromosome 17. Our embryological and molecular studies indicate that this chromosome (twLub2) is characterized by both a deletion and duplication of adjacent genetic material. The deletion appears to be responsible for a dominant lethal maternal effect and a recessive embryonic lethality. The duplication provides an explanation for the twLub2 suppression of the dominant T locus phenotype. A reanalysis of previously described results with another chromosome 17 variant called TtOrl indicates a structure for this chromosome that is reciprocal to that observed for twLub2. We have postulated the existence of an inversion over the proximal portion of all complete t haplotypes in order to explain the generation of the partial t haplotypes twLub2 and TtOrl. This proximal inversion and the previously described distal inversion are sufficient to account for all of the recombination properties that are characteristic of complete t haplotypes. The structures determined for twLub2 and TtOrl indicate that rare recombination can occur between nonequivalent genomic sequences within the inverted proximal t region when wild-type and t chromosomes are paired in a linear, nonhomologous configuration.

Alleles↗

Genetic analysis of a mouse t complex locus that is homologous to a kidney cDNA clone.

A mouse kidney cDNA clone, pMK174, identifies restriction fragment length polymorphisms (RFLPs) that map to two unlinked loci. One, designated D17Rp17, has been mapped near quaking, (qk), on chromosome 17 using three sets of recombinant inbred (RI) strains. A study of several t haplotypes resulted in the identification of t-specific alleles of D17Rp17 that map to the proximal half of the t complex. Neither t-specific nor wild-type D17Rp17 alleles are present in chromosomes carrying either the T Orleans (TtOrl) or the T hairpin tail (Thp) deletions. Comparison with other molecular markers indicates that pMK174 identifies a new proximal t complex locus, Rp17. The second locus identified by pMK174, termed D4Rp18, is tentatively assigned to chromosome 4 by mouse-Chinese hamster somatic cell hybrid analysis.

Alleles↗

Assignment of pancreatic ribonuclease gene to mouse chromosome 14.

A pancreatic ribonuclease cDNA was used as a probe for Southern blot hybridization of genomic DNA from recombinant inbred strains of mice. The results indicated that the gene coding for pancreatic ribonuclease (Rib-1) can be assigned to mouse chromosome 14. Analysis of the congenic strain B10.D2(57N)Sn confirmed this assignment and indicated that Rib-1 is closely linked to the genes encoding the T-cell receptor alpha subunit (Tcra) and nucleoside phosphorylase-2 (Np-2).

Alleles↗

Linkage of genes for laminin B1 and B2 subunits on chromosome 1 in mouse.

We have used cDNA clones for the B1 and B2 subunits of laminin to find restriction fragment length DNA polymorphisms for the genes encoding these polypeptides in the mouse. Three alleles were found for LamB2 and two for LamB1 among the inbred mouse strains. The segregation of these polymorphisms among recombinant inbred strains showed that these genes are tightly linked in the central region of mouse Chromosome 1 between Sas-1 and Ly-m22, 7.4 +/- 3.2 cM distal to the Pep-3 locus. There is no evidence in the mouse for pseudogenes for these proteins.

Alleles↗

Urographic findings in adults with chronic pyelonephritis.

The radiological findings in a cohort of 138 adults with chronic pyelonephritis are presented and the following conclusions made. Scarring is commoner in the right kidney than the left and is found in the upper, middle and lower poles with decreasing frequency from above down. Agreement between observers in the grading of scarring in urograms taken without standardisation or routine tomography, is sufficiently high to justify the continued use of the intravenous urogram as a screening test but is not high enough to detect any progression of scars in the group over a 6.5-year period. Repetition of urograms seldom reveals the development of calculi or other new abnormalities and is not justified as a clinical routine. The combination of extensive bilateral renal scarring and proteinuria is associated with the worst renal function.

Adult↗

Surgical aspects of continuous ambulatory peritoneal dialysis--3 years experience.

Since January 1979, 122 patients (mean age 38.5 years, range 5-72 years) with chronic renal failure have been treated with continuous ambulatory peritoneal dialysis (CAPD). Peritoneal access was achieved by inserting silicone rubber Tenckhoff peritoneal dialysis catheters (Quinton, Seattle, Washington) by an open (76 per cent) or closed technique. Actuarial analysis showed a patient survival of 98 and 94 per cent and a success rate of 88 and 64 per cent at 1 and 2 years, respectively. Currently, 74 patients are using CAPD and 8 have been treated for 30-36 months. Thirty-five patients (29 per cent) required two or more peritoneal catheters and 69 per cent of these patients are still on CAPD. Catheter-related peritonitis was the most frequent complication (233 separate episodes in 94 patients) and necessitated catheter removal in 16 per cent of episodes, although 37 per cent of patients from whom catheters were removed because of peritonitis later resumed CAPD. Extravasation of dialysate from the peritoneal cavity (31 episodes) and catheter obstruction (31 episodes) required surgical replacement of catheters in 8 and 23 cases, respectively. Twenty patients (16 per cent) developed 24 abdominal hernias, only one of which caused failure of CAPD. Infective and mechanical complications of CAPD frequently require surgical intervention but only occasionally result in failure of the technique, and even multiple catheter replacements are compatible with successful long term CAPD.

Abdomen↗

Osteomalacia due to ileal replacement of ureters: report of 2 cases.

We report 2 cases of ileal replacement of the ureters: 1 bilateral and 1 unilateral with a single kidney. Hyperchloremic acidosis developed in both patients and osteomalacia was proved by iliac bone biopsy. Patient 1 had symptomatic bone disease and control of acidosis with sodium bicarbonate was difficult because of associated hypertension. The level of alkaline phosphatase varied inversely with the level of serum bicarbonate. Pharmacological doses of 1-alpha hydroxycholecalciferol were ineffective and osteomalacia persisted in a second biopsy. Patient 2, who was asymptomatic, suffered acidosis and increased serum alkaline phosphatase levels immediately postoperatively and osteomalacia was confirmed histologically at 6 months.

Acidosis↗

DNA sequence polymorphism in an androgen-regulated gene is associated with alteration in the encoded RNAs.

We have used plasmid pMK908, whose cDNA insert corresponds to an androgen-inducible RNA from mouse kidney, as a probe to study both the complementary genomic DNA and the encoded RNA sequences in several inbred strains of mice. A polymorphism in the 908 structural gene, revealed by Southern blotting of HindIII-generated DNA fragments, was found to map near the Gpi-1 and Tam-1 loci on chromosome 7. The 908 structural gene has been termed RP2. The 908 RNAs constitute a sequence-related group displaying extensive size heterogeneity. This heterogeneity, reflected in the size distribution of the RNA on electrophoretic blots, is controlled by a genetic site that is tightly linked to RP2. Thus, associated with polymorphism at RP2 is a change in the molecular size pattern of encoded transcripts.

Alleles↗

Identification of a cDNA clone for mouse apoprotein A-1 (apo A-1) and its use in characterization of apo A-1 mRNA expression in liver and small intestine.

A cDNA clone for mouse apoprotein A-1 (apo A-1), the major apoprotein of plasma high density lipoproteins, has been identified. In addition to structural and physiological evidence, a genetic polymorphism for mouse plasma apo A-1 has been used to confirm that this DNA sequence corresponds to the apo A-1 gene. Use of this clone in molecular hybridization studies has shown that the concentration of apo A-1 mRNA is similar in liver and small intestine and is constant along the entire length of the small intestine. We provide evidence that the same apo A-1 gene is expressed in both liver and small intestine. Apo A-1 mRNA is also present in the stomach and esophagus at 10-15% the concentration found in small intestine but is undetectable in other tissues (such as large intestine, pancreas, heart, kidney, spleen, and brain). Finally, we show that there is a differential effect of a diet high in saturated fat and cholesterol on apo A-1 mRNA levels in liver and small intestine.

Animals↗

Intravenous methylprednisolone at the time of renal transplantation.

Ninety-five consecutive transplants performed prior to the introduction of methylprednisolone bolus at transplantation were compared to 136 consecutive transplants performed after the policy change. No difference was found in the incidence of reversible or irreversible rejection in the two groups. The treated group were exposed to a higher total dose of steroid than the non-treated group. Routine bolus methylprednisolone therapy at transplantation is not recommended.

Adult↗

Superiority of B locus matching over other HLA matching in renal graft survival.

Graft survival after 348 consecutive first cadaver-donor renal transplants was significantly improved by HLA matching when recipients who had received pretransplant blood transfusions were matched with their kidney donor for two HLA-B locus antigens. No other type of HLA matching significantly improved graft survival in transfused recipients nor did any type of HLA matching in non-transfused recipients. Matching for one HLA-DR antigen had no benefit in transfused recipients. Only two patients received kidneys matched for both DR antigens and only two of those in whom DR matching had been performed had not been transfused. These results indicate that pretransplant blood transfusion and selection of graft recipients predominantly on the basis of HLA-B matching has significantly reduced the renal graft rejection rate in Newcastle upon Tyne over two years. Thus, HLA-B antigen matching should be adopted as the main criterion for kidney sharing between transplant centres.

Adult↗