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D R Love

Publications and source records attributed to D R Love.

At least 73 records · Page 4Linked to original sources
PubMed1990

Characterization of deletions in the dystrophin gene giving mild phenotypes.

We have characterized deletions of the dystrophin gene in patients suffering from relatively mild muscular dystrophy. Our data show that most of the Becker muscular dystrophy (BMD) patients have intragenic deletions which leave the protein reading frame in phase. Remarkably, large deletions of the region corresponding to the central triple helical repeats in the protein can result in an exceptionally mild phenotype. Three brothers suffering from BMD, glycerol kinase deficiency, and adrenal hypoplasia possess a deletion at the 3' end of the gene. They also display developmental delay. Thus the 3' processing of the gene must be necessary for the correct function of the dystrophin molecule.

Adrenal Glands↗
PubMed1990

Localisation of a dystrophin-related autosomal gene to 6q24 in man, and to mouse chromosome 10 in the region of the dystrophia muscularis (dy) locus.

We have localised a dystrophin-related autosomal gene called DMDL (Duchenne muscular dystrophy-like) to human chromosome 61q24 by in situ hybridisation. Using restriction fragment length polymorphism analysis in two mouse species, we have localised the homologous gene Dmdl in the mouse to chromosome 10 proximal to the Myb oncogene. A neuromuscular disease locus dystrophia muscularis (dy) has previously been assigned to this region of mouse chromosome 10.

Animals↗
PubMed1990

Physical mapping distal to the DMD locus.

We report a new locus, designated JC-1, which maps between the gene responsible for adrenal hypoplasia (AHC) and the gene that encodes glycerol kinase (GK) in Xp21.2-21.3. The probe identifying this locus was obtained by cloning the distal sequence of a junction fragment from a Duchenne muscular dystrophy (DMD) patient with a large deletion. Pulsed-field gel electrophoresis analysis shows that a region of at least 4 Mb separates the 3' end of the dystrophin gene and the closest distal marker to AHC, DXS28. This region of the human genome contains few genes whose deletion results in a clinical phenotype. JC-1 is a useful probe from which to initiate strategies directed at cloning the AHC and GK loci.

Blotting, Southern↗
PubMed1990

celB, a gene coding for a bifunctional cellulase from the extreme thermophile "Caldocellum saccharolyticum".

"Caldocellum saccharolyticum" is an obligatory anaerobic thermophilic bacterium. A gene from this organism, designated celB, has been cloned in Escherichia coli as part of a bacteriophage lambda gene library. This gene produces a thermostable cellulase that shows both endoglucanase and exoglucanase activities on test substrates and is able to degrade crystalline cellulose to glucose. The sequence of celB has homology with both exo- and endoglucanases described by others. It appears to have a central domain without enzymatic activity which is joined to the enzymatic domains by runs of amino acids rich in proline and threonine (PT boxes). Deletion analysis shows that the exoglucanase activity is located in the amino-terminal domain of the enzyme and that endoglucanase activity is located in the carboxy-terminal domain. There are internal transcriptional and translational start sites within the gene. The intact gene has been cloned into a temperature-inducible expression vector, pJLA602, and overexpressed in E. coli. Polyacrylamide gel electrophoresis showed that celB produced a protein with a molecular weight of 118,000 to 120,000. A number of smaller proteins with activity against carboxymethyl cellulose and 4-methyl umbelliferyl-beta-D-cellobioside were also produced. These are believed to be the result of alternative translational start sites and/or proteolytic degradation products of the translated gene product.

Amino Acid Sequence↗
PubMed1990

Cloning, sequence analysis, and expression of genes encoding xylan-degrading enzymes from the thermophile "Caldocellum saccharolyticum".

A lambda recombinant bacteriophage coding for xylanase and beta-xylosidase activity has been isolated from a genomic library of the extremely thermophilic anaerobe "Caldocellum saccharolyticum." Partial Sau3AI fragments of the lambda recombinant DNA were ligated into pBR322. A recombinant plasmid with an insertion of ca. 7 kilobases of thermophilic DNA expressing both enzymatic activities was isolated. The location of the genes has been established by analyzing deletion derivatives, and the DNA sequence of 6.067 kilobases of the insert has been determined. Five open reading frames (ORFs) were found, one of which (ORF1; Mr 40,455) appears to code for a xylanase (XynA) which also acts on o-nitrophenyl-beta-D-xylopyranoside. Another, ORF5 (Mr 56,365), codes for a beta-xylosidase (XynB). The xynA gene product shows significant homology with the xylanases from the alkalophilic Bacillus sp. strain C125 and Clostridium thermocellum.

Amino Acid Sequence↗
PubMed1989

An autosomal transcript in skeletal muscle with homology to dystrophin.

The Duchenne muscular dystrophy (DMD) gene has been localized to chromosome Xp21 and codes for a 14-kilobase (kb) transcript and a protein called dystrophin, of relative molecular mass 427,000. Dystrophin is associated with the cytoplasmic face of muscle fibre membranes and its C-terminal domain is thought to mediate membrane attachment. Although N-terminal and central domain structures share common features with other cytoskeletal components, no significant sequence similarity between the C-terminal region of dystrophin and other previously characterized proteins has been described. Here we report that fragments from the C-terminal domain of the DMD complementary DNA detect a closely related sequence which exhibits nucleic-acid and predicted amino-acid identities with dystrophin of approximately 65 and 80%, respectively. The dystrophin-related sequence identifies a 13-kb transcript in human fetal muscle and maps to chromosome 6. Thus, dystrophin may be a member of a family of functionally related large structural proteins in muscle.

Base Sequence↗
PubMed1989

Molecular analysis of Duchenne and Becker muscular dystrophies.

The analysis of DNA from patients suffering from Duchenne (DMD) and Becker (BMD) muscular distrophies has resulted in the identification of a single gene locus for these diseases. The locus is deleted to varying extents in affected patients. The translation product of this locus has been implicated as the site of the primary biochemical defect responsible for these muscle disorders. There is no simple correlation between the severity of the clinical phenotype and the location and extent of genomic deletions in the DMD locus. This lack of correlation may be due, in part, to the difficulties inherent in examining a gene of complex arrangement, with exons distributed over a large genomic distance. This paper examines the location of deletion breakpoints in DMD and BMD patients. The molecular analysis of these deletions are presented in the context of transcriptional and translational studies of DMD gene expression and the manifestation of the clinical phenotype.

Chromosome Deletion↗
PubMed1988

Sequence structure and expression of a cloned beta-glucosidase gene from an extreme thermophile.

The gene for a beta-glucosidase from the extremely thermophilic bacterium Caldocellum saccharolyticum has been isolated from a genomic library and sequenced. An open reading frame identified by computer analysis of the sequence could encode a protein of Mr 54,400, which is close to the size of the polypeptide experimentally determined using maxicells. Analysis of the amino-terminal residues of the protein produced in Escherichia coli suggests that it is processed by a methionine aminopeptidase. A sequence within C. saccharolyticum DNA upstream of the beta-glucosidase gene was found to act as a promoter for expression of the thermophile gene in E. coli. The protein has been overproduced in E. coli and Bacillus subtilis where it retains its enzymatic activity and heat stability. There appears to be a single copy of the gene in Caldocellum DNA.

Amino Acid Sequence↗
PubMed1987

Expression of leucine genes from an extremely thermophilic bacterium in Escherichia coli.

The organisation of the leucine genes in Thermus thermophilus HB8 was analysed by examining the ability of recombinant DNAs to complement Escherichia coli mutations. The arrangement of the genes is different from that in the mesophilic bacteria E. coli and Salmonella typhimurium. The promoter responsible for the expression of the leuB, leuC and leuD genes of Thermus HB8 in E. coli was identified. The sequence of Thermus DNA containing this promoter revealed structural similarities to the promoter and attenuator regions of the E. coli leucine operon.

3-Isopropylmalate Dehydrogenase↗
PubMed1984

Terminal care: the role of the general practitioner hospital.

A survey of all deaths occurring over a two-year period in a group practice population was carried out to assess the contribution of the local general practitioner hospital to terminal care overall. With the availability of the hospital, the general practitioners were able to provide a higher proportion of terminal care for their patients than in areas where general practitioners did not have access to hospital beds. This was particularly so in terminal care for patients dying of cancer.

Aged↗
PubMed1971

An unusual case of self-induced electrolyte depletion.

A case of anorexia nervosa, presenting with unexplained hypokalaemia, is described. The patient was also secretly addicted to purgatives and diuretics. During an attempted metabolic balance study she secretly disposed of food and excreta, which were smuggled from the hospital by her sister. The patient induced her husband to bring his own stools into the ward, these then being substituted for her own. The interrelationships of the electrolyte disturbances, elevation of plasma renin, renin substrate, and hyperaldosteronism are discussed, particularly in connexion with the pathogenesis of peripheral oedema in anorexia nervosa.

Adult↗
PubMed1971

Orthostatic hypotension and the Holmes-Adie syndrome. A study of two patients with afferent baroreceptor block.

Two patients who presented with symptoms due to orthostatic hypotension were found on examination to have the Holmes-Adie syndrome. Physiological investigation suggested that they both had an afferent block from baroreceptors in contrast to the efferent autonomic block found in most other cases of idiopathic orthostatic hypotension, including the cases of multisystem disease, now often called the Shy-Drager syndrome.

Adie Syndrome↗