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Biomedical subjects

L Stubbs

Publications and source records attributed to L Stubbs.

At least 55 records · Page 3Linked to original sources
PubMed1996

Aspirin changes the secretion rate and amino acid composition of human small intestinal mucin in subjects with ileal conduits.

The effect of aspirin on the rate of secretion and amino acid composition of human ileal mucin was studied, using subjects with ileal conduits as a model system in which mucin secreted from the ileal conduit tissue is flushed out in the urine and can be measured and analysed. Aspirin (600 mg per day, administered orally) increased the daily mucin output by 37-104% in subjects by days 3 or 4, but thereafter the mucin output declined to below the baseline level by day 10. Mucin samples, purified from the ileal conduit urine during the control period and during aspirin administration, were compared. There were no discernible changes in the degree of polymerisation or the density, but during aspirin administration the amino acid composition was significantly changed, and in particular threonine and proline were enriched. One possible explanation, consistent with the compositional analyses, is that the N- and C-terminal regions of the mucin subunits have been cleaved off and lost during aspirin administration. The observed changes in mucin secretion may have implications for the mechanism of the toxic effects of aspirin on the small intestine by altering the barrier properties of the mucus layer.

Amino Acids↗
PubMed1994

Clustering of six human 11p15 gene homologs within a 500-kb interval of proximal mouse chromosome 7.

Homologs of genes mapping to human chromosome 11p15 are located in three distinct, widely separated regions of mouse chromosome 7 (Mmu7). To date, six genes have been localized to the most proximal HSA11p15/Mmu7 homology region, including Ldh3 (encoding lactate dehydrogenase C), Ldh1 (lactate dehydrogenase A), Myod1 (myogenic differentiation factor-1), Tph (tryptophan hydroxylase), Saa1 (serum amyloid-A-1), and Kcnc1 (encoding a Shaw-type voltage-gated potassium channel). To define the overall size and organization of this region of Mmu7, we have established a long-range physical map including the murine Ldh1, Ldh3, Saa, Tph, Kcnc1, and Myod1 genes. Our results demonstrate that these six genes are physically clustered and are distributed throughout a 500-kb interval located just proximal of the pink-eyed dilution (p) locus. These data, together with recent mapping studies within the related region of HSA11p15, demonstrate that gene content and organization within this proximal homology segment have been highly conserved throughout evolution.

Animals↗
PubMed1994

Genomic organization and expressed sequences of the mouse extended H-2K region.

The mouse major histocompatibility complex (MHC) has long been of great interest to many biologists because of not only its critical role in the immune system, but also its association with at least three embryonic lethal genes. Here, we present an analysis of the mouse extended H-2K region using YAC technology. Six new expressed sequences were identified, demonstrating that the high gene density previously described continues. Restriction mapping of a YAC clone extending proximal of the MHC region defined a CpG-rich region located up to 320 kb away from H-2K. The absence of any CpG-rich region for a distance spanning approximately 200 kb near the YAC's proximal end suggests that the high gene density probably diminishes at a distance of 360 kb away from H-2K. The description of genomic organization of both H-2K and the extended H-2K region provides insight into the characteristics of this whole region with respect to gene diversity and density.

Animals↗
PubMed1994

Molecular analysis of mouse Rab11b: a new type of mammalian YPT/Rab protein.

Since the realization that the vesicular transport machinery is conserved from yeast to vertebrate neurons, much interest in the proteins involved has been generated. Here we describe a new type of mammalian YPT/Rab protein, named Rab11b, that is most abundantly expressed in brain, heart, and testis. It has all the hallmarks of a YPT3/Rab11 protein, but is more closely related to a ypt3-related gene isolated from fish (97% homology) than to the previously described four mammalian Rab11 genes (89% homology). The mammalian Rab11 genes discovered previously are, by contrast, 100% identical to each other. The genomic structure of a mammalian Rab11 protein is described for the first time. It is surprisingly asymmetrical, with 96% of the coding sequence contained in one-third of the transcription unit. Two copies of this gene are mapped to mouse chromosomes 1 and 17. The fine structural analysis of Rab11b and the protein sequence comparison provides a close look at all YPT3/Rab11-related genes cloned so far and clues to their possible relationship.

Amino Acid Sequence↗
PubMed1993

Concordance between isolated cleft palate in mice and alterations within a region including the gene encoding the beta 3 subunit of the type A gamma-aminobutyric acid receptor.

Genetic and molecular analyses of a number of radiation-induced deletion mutations of the pink-eyed dilution (p) locus in mouse chromosome 7 have identified a specific interval on the genetic map associated with a neonatally lethal mutation that results in cleft palate. This interval, closely linked and distal to p, and bracketed by the genes encoding the alpha 5 and beta 3 subunits of the type A gamma-aminobutyric acid receptor (Gabra5 and Gabrb3, respectively), contains a gene(s) (cp1; cleft palate 1) necessary for normal palate development. The cp1 interval extends from the distal breakpoint of the prenatally lethal p83FBFo deletion to the Gabrb3 locus. Among 20 p deletions tested, there was complete concordance between alterations at the Gabrb3 transcription unit and inability to complement the cleft-palate defect. These mapping data, along with previously described in vivo and in vitro teratological effects of gamma-aminobutyric acid or its agonists on palate development, suggest the possibility that a particular type A gamma-aminobutyric acid receptor that includes the beta 3 subunit may be necessary for normal palate development. The placement of the cp1 gene within a defined segment of the larger D15S12h (p)-D15S9h-1 interval in the mouse suggests that the highly homologous region of the human genome, 15q11-q13, be evaluated for a role(s) in human fetal facial development.

Animals↗
PubMed1993

The alpha 2(XI) collagen gene lies within 8 kb of Pb in the proximal portion of the murine major histocompatibility complex.

A number of serious hereditary disorders are now known to be associated with defective expression of collagen genes, and these findings have underscored the important and varied roles that the collagen family of genes must play during normal mammalian development. Although the activities of genes encoding the quantitatively major types of collagen are fairly well characterized, functions of the many minor types of collagen remain a matter of speculation. As a first step toward a functional analysis of type XI collagen, a member of this class of poorly understand "minor" collagen proteins which is expressed primarily in hyaline cartilage, we have used human probes for the gene encoding the protein's alpha 2-subunit (COL11A2) to isolate and map homologous murine DNA sequences. Our results demonstrate that Col11a-2 is embedded within the major histocompatibility complex (MHC), within 8.4 kb of the class II pseudogene locus, Pb, and confirm that human and murine alpha 2(XI) collagen genes are located in very similar genomic environments. The conserved location of these genes raises the possibility that type XI collagen genes may contribute to one or more of the diverse hereditary disorders known to be linked to the MHC in mouse and human.

Amino Acid Sequence↗
PubMed1993

A double blind placebo controlled trial of medroxyprogesterone acetate (MPA) in cancer cachexia.

Patients with breast cancer treated with MPA often report an improvement in appetite. Similar appetite stimulation is seen in patients treated with some corticosteroids, but MPA has a potential advantage over these drugs in that it does not exert a catabolic effect. MPA (100 mg tds orally) has therefore been compared with placebo in 60 patients with advanced malignant disease. Twenty-one patients in the MPA group and 20 in the placebo group were receiving chemotherapy. Patients were treated for 6 weeks and were assessed at weeks 0, 3 and 6 for appetite, energy, mood and pain using visual analogue scales. Nutritional status was assessed by the measurement of serum proteins and anthropometrics. Karnofsky score was recorded as a measure of performance status. There was a significant improvement in appetite in the MPA group between weeks 0 (pre-study) and 3 (P = 0.0002) and 0 and 6 (P = 0.015). There was no significant improvement in appetite in the placebo group. Supporting this finding was the significant increase in serum thyroid binding pre-albumin and retinol binding protein in the MPA group between weeks 0 and 3 and 0 and 6 (P = 0.023 and P = 0.039 respectively). These two parameters showed no significant change in the placebo group. There was no change in anthropometric measurements, weight, performance status, energy, mood or pain in either group. These data indicate that there was a significant increase in appetite in anorexic patients with advanced cancer treated with MPA which was reflected in increases in rapid turnover proteins reported to reflect nutritional status. However, this apparent increase in appetite did not result in improved weight, performance status, energy levels, mood or relief of pain. Further studies to investigate the effect of higher doses of MPA are indicated.

Appetite↗
PubMed1991

The mouse Col2a-1 gene is highly conserved and is linked to Int-1 on chromosome 15.

Type II collagen is the major extracellular matrix component of cartilage and correct expression of the alpha 1(II) collagen gene is important for vertebrate skeletal development. In order to provide the basis for studying the control of type II collagen gene expression in embryogenesis and in mouse models of human connective tissue disease, the complete mouse Col2-a1 gene has been isolated in a single cosmid clone, cosMco1.2, and partially characterized. The gene is approximately 30 kb and is highly conserved in exon/intron structure and nucleotide and amino acid sequence (greater than 80% homology) when compared with the human, rat, bovine and chicken equivalents. A high degree of conservation was also found in the 5' flanking region of the rat, human and mouse alpha 1(II) collagen genes, including the presence of several G + C and C + T rich, direct repeat motifs. The sites of transcription start, termination codon and polyadenylation have also been identified. Unlike chicken, bovine and human, where polyA attachment is at a single site, for the mouse Col2a-1 gene two polyadenylation sites are utilized. Col2a-1 has also been localized by interspecies backcross analysis to the central portion of mouse Chromosome (Chr) 15, approximately 8 centiMorgans (cM) proximal of Int-1 and 18 cM distal of Myc. Col2a-1 is therefore included in a linkage group which is conserved on human Chr 12q.

Amino Acid Sequence↗
PubMed1990

Attitudes to chemotherapy: comparing views of patients with cancer with those of doctors, nurses, and general public.

OBJECTIVE: To compare responses of patients with cancer with those of a matched control group, cancer specialists, general practitioners, and cancer nurses in assessing personal cost-benefit of chemotherapy. DESIGN: Prospective study of consecutively recruited patients with cancer and other groups by questionnaire; half of the patients received the questionnaire again three months after starting treatment. SETTING: A medical oncology ward of a London teaching hospital. SUBJECTS: 106 Patients with newly diagnosed solid tumours referred to the unit for consideration of treatment with cytotoxic chemotherapy, 100 of whom were able to complete the questionnaire. 100 Matched controls, 315 cancer doctors (238 radiotherapists and 77 medical oncologists), 1500 randomly chosen general practitioners, and 1000 randomly chosen cancer nurses. MAIN OUTCOME MEASURES: Percentage chance of cure, prolonging life, or palliation of symptoms required to make treatment worth while with two hypothetical chemotherapy treatments, with severe and mild side effects respectively. RESULTS: Respondents to the questionnaire comprised 100 patients, 100 controls, 60 (78%) medical oncologists, 88 (37%) radiotherapists, 790 (53%) general practitioners, and 303 (30%) cancer nurses. Most patients were willing to accept intensive chemotherapy for a very small chance of benefit. The median benefit required to make the hypothetical intensive treatments worth while for patients compared with controls were: for chance of a cure (range 1 to 100%) 1% v 50%, for prolonging life (range three months to five years) 12 months v 24-60 months, and for relief of symptoms (range 1 to 100%) 10% v 75% respectively. There were no significant differences in the responses of the 50 patients completing the questionnaire on a second occasion. Doctors and nurses were less likely to accept radical treatment for minimal benefit compared with the patients (median scores 10-50%, 12-24 months, and 50-75%, for chance of cure, prolonging life, and relief of symptoms respectively). Significantly more patients than controls accepted treatments giving the minimal benefit for each category (cure 53.1 v 19.0%, 67.0 v 35.0%; prolonging life 42.1 v 10.0%, 53.0 v 25.0%; relief of symptoms 42.6 v 10.0%, 58.7 v 19.0% for intensive and mild treatments respectively, p less than 0.001) as was the case for comparison of patients with other groups. CONCLUSION: Patients with cancer are much more likely to opt for radical treatment with minimal chance of benefit than people who do not have cancer, including medical and nursing professionals. This could be taken into account when discussing treatment options with patients and their relatives.

Antineoplastic Agents↗
PubMed1990

The murine genes Hox-5.1 and Hox-4.1 belong to the same HOX complex on chromosome 2.

Two different loci of Antennapedia-related homeobox-containing genes have been shown to map to mouse chromosome 2: the HOX-5 complex and the Hox-4.1 gene. These independently derived loci are likely to be parts of a single gene complex, although their close linkage has not yet been demonstrated. Since cosmid walks to extend the HOX-5 cluster and to potentially link the two loci were unsuccessful, we have used large restriction fragments separated by pulsed-field gel electrophoresis to demonstrate the linkage between probes from the HOX-5 region and sequences near Hox-4.1. To further define the distance between the two linked loci, we screened a NotI jumping library with sequences near the Hox-5.1 gene to obtain a marker within the region predicted to contain Hox-4.1. The jumping endpoint lies within genomic clones from a lambda phage walk extending from the 5' end of Hox-4.1, and thus provides clear evidence of linkage between the two Hox loci. Our results demonstrate that Hox-4.1 lies approximately 35 kb downstream of the Hox-5.1 gene and that the two loci do indeed thus constitute parts of the same HOX complex.

Animals↗
PubMed1990

The HOX-5 and surfeit gene clusters are linked in the proximal portion of mouse chromosome 2.

Using an interspecies backcross, we have mapped the HOX-5 and surfeit (surf) gene clusters within the proximal portion of mouse chromosome 2. While the HOX-5 cluster of homeobox-containing genes has been localized to chromosome 2, bands C3-E1, by in situ hybridization, its more precise position relative to the genes and cloned markers of chromosome 2 was not known. Surfeit, a tight cluster of at least six highly conserved "housekeeping" genes, has not been previously mapped in mouse, but has been localized to human chromosome 9q, a region of the human genome with strong homology to proximal mouse chromosome 2. The data presented here place HOX-5 in the vicinity of the closely linked set of developmental mutations rachiterata, lethargic, and fidget and place surf close to the proto-oncogene Abl, near the centromere of chromosome 2.

Animals↗
PubMed1990

Location of the gene involving the small eye mutation on mouse chromosome 2 suggests homology with human aniridia 2 (AN2).

Using an interspecific backcross, we have mapped the gene involved in the mouse Small eye mutation (SeyMH) relative to six cloned markers on chromosome 2 (Hox-5.1, Cas-1, Fshb, Bmp-2a, and ld) and the agouti locus. The results suggest that the Sey gene maps between Fshb and Cas-1. Human mapping studies have shown that the aniridia (AN2) gene, which is part of the Wilms tumor susceptibility, aniridia, genitourinary abnormalities, and mental retardation (WAGR) complex, is also between FSHB and CAT on human chromosome 11. The conserved linkage of the cloned markers and the similarity of the Sey/+ and AN2/+ phenotypes suggest that the gene involved in the Sey mutation is the mouse homolog of the human AN2 gene.

Animals↗