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Biomedical subjects

C Morris

Publications and source records attributed to C Morris.

At least 19 recordsLinked to original sources
PubMed1992

Clonal development and karyotype evolution during leukemogenesis of BCR/ABL transgenic mice.

The Philadelphia (Ph) translocation is responsible for the generation of the chimeric BCR/ABL oncogene. The Ph chromosome constitutes the earliest detectable chromosome abnormality in chronic myelogenous leukemia and is also found in acute lymphoblastic leukemia. Mice transgenic for a P190 BCR/ABL-producing DNA construct develop lymphoblastic leukemia/lymphoma and provide an opportunity to study early stages of the disease as well as progression. In this study, we have karyotyped the bone marrow of 10 19-day-old BCR/ABL P190 transgenic mice from a line that reproducibly develops leukemia/lymphoma. Leukemic cells from 17 terminally ill transgenic founders and progeny were also karyotyped as well as bone marrow transplant recipients of leukemic donor marrow. Karyotypically visible aberrations were absent from the early stages of BCR/ABL P190-generated leukemia and normal metaphases could be found even in the terminal stages of the disease. A high frequency of aneuploidy was found in advanced leukemia, with a marked preference for the gain of mouse chromosomes 12, 14, or 17. These results point to a primary role for BCR/ABL in leukemogenesis and suggest a destabilizing effect of the BCR/ABL gene on the regulation of cell division.

Aneuploidy↗
PubMed1992

Chromosomal localization of the human glycoasparaginase gene to 4q32-q33.

Glycoasparaginase cleaves the N-glycosidic linkage between asparagine and N-acetylglucosamine in the degradation of glycoproteins. In humans, a deficient activity of glycoasparaginase results in accumulation of glycoasparagines, causing the lysosomal storage disease aspartylglycosaminuria. Recombinant plasmid containing the cDNA insert encoding human glycoasparaginase was used to localize the enzyme to chromosome 4q32-q33 by in situ hybridization to metaphase chromosomes prepared from normal human lymphocytes.

Aspartylglucosylaminase↗
PubMed1992

The outcome of unexplained dyspepsia. A questionnaire follow-up study of patients after endoscopy.

Ninety-three consecutive patients referred to a gastroenterology unit with unexplained dyspeptic symptoms were sent a postal questionnaire 6-12 months after endoscopy. It inquired into their current physical symptoms and subjective improvement since investigation, satisfaction with treatment, past history and current psychological well-being. A comparison group of 47 patients with peptic disease were similarly surveyed. Those with unexplained dyspepsia reported more current physical symptoms, more dissatisfaction with their treatment and less subjective improvement than those with peptic disease. The two groups were similar in terms of psychological distress but previous consultation for abdominal and other somatic complaints were more common in those with unexplained dyspepsia. The implications for management of dyspeptic patients are discussed.

Adult↗
PubMed1992

Effects of platelet-activating factor on prostaglandin E2 production by intact fetal membranes.

OBJECTIVE: The hypothesis tested in this study is that platelet-activating factor increases prostaglandin E2 synthesis from fetal membranes. STUDY DESIGN: Fetal membrane disks obtained before or after labor were incubated with or without platelet-activating factor for time periods of up to 24 hours. The production of prostaglandin E2 and its inactive metabolites was determined by specific radioimmunoassays. RESULTS: Platelet-activating factor (1 to 10 mumol/L) stimulated the production of prostaglandin E2 and its metabolites by intact fetal membranes and chorion-decidua threefold to fourfold after 24 hours of incubation. Platelet-activating factor had far greater effects on the production of prostaglandin E2 by intact fetal membranes obtained after the onset of labor, such that prostaglandin E2 production was increased by tenfold to 100-fold. CONCLUSION: These results suggest that platelet-activating factor mainly stimulates prostaglandin E2 production by the chorion-decidua before labor and that it may act in synergism with other stimulatory factors present in the fetal membranes during labor.

Amnion↗
PubMed1992

Bone marrow cells from A/J mice do not proliferate in interleukin-3 but express normal numbers of interleukin-3 receptors.

Haemopoietic cells from A/J mice do not form colonies (proliferate) in response to interleukin-3 (multi-CSF, IL-3). We have examined different populations of cells from A/J mice and shown that, despite their failure to proliferate in response to IL-3, cells from bone marrow, spleen and the peritoneum all bound 125I-labelled IL-3. A wide variety of cell types bound IL-3 as determined by autoradiography, including promyelocytes, myelocytes, metamyelocytes, polymorphs, promonocytes, monocytes, eosinophils and lymphocytes, but not nucleated erythroid cells, and the proportion of each cell type binding label was similar when cells from A/J mice were compared with those of C57B1/6 and Balb/c mice. Bone marrow cells from A/J mice internalized interleukin-3 with normal kinetics and mRNA extracted from these cells contains the same species of IL-3 receptor and IL-3 receptor-like mRNAs as are found in the other strains. Collectively the data suggest that the failure of haemopoietic cells from A/J mice to proliferate in response to IL-3 is related to a selective defect in signalling to proliferation specific genes. This defect is apparently not related to internalization or processing of the IL-3/IL-3-receptor complex, but may be due to failure to activate appropriate accessory molecules in the cell.

Animals↗
PubMed1992

Transfer and metabolism of platelet-activating factor by fetal membranes, amnion and chorio-decidua.

OBJECTIVE: To determine the metabolism of 3H-Platelet-activating factor (3H-PAF) during transfer through human fetal membranes. DESIGN: 3H-PAF was added to the fetal side of cultured intact fetal membranes, amnion and chorio-decidua obtained from three pregnancies ending in elective caesarean section. MAIN OUTCOME MEASURES: Radioactivity was measured on both sides of the tissue, and in the tissue itself. In some experiments, the metabolism of 3H-PAF was assessed by thin-layer chromatography. RESULTS: Very little 3H-PAF crossed the intact fetal membrane (< 2%) during 24 h of culture. Most of the 3H-PAF which accumulated in the membrane was converted to a range of metabolites in the chorio-decidua. CONCLUSIONS: These results suggest that PAF in amniotic fluid may not reach the decidua, and therefore is unlikely to be involved in the control of prostaglandin production from this tissue.

Amniotic Fluid↗
PubMed1992

Recognition of upper airway obstruction misdiagnosed as asthma.

Distinguishing new onset asthma from an insidious upper airway obstruction can prove difficult and is more frequently being addressed in the medical literature. We examine our experience in a teaching hospital and analyze the problems relating to establishing the correct diagnosis.

Adult↗
PubMed1992

The susceptibility of the Indonesian I/CDC strain of Plasmodium vivax to chloroquine.

A strain of Plasmodium vivax from Indonesia was adapted to splenectomized Aotus and Saimiri monkeys and tested for its susceptibility to chloroquine. Animals were infected by intravenous inoculation of heparinized parasitized blood and subsequently treated with 8 or 15 mg (base) of chloroquine by oral intubation. Recrudescence of infection occurred in 4 of 4 Aotus and 5 of 6 Saimiri monkeys treated with 15 mg base of chloroquine, indicating a level of resistance between that of the standard Chesson strain of P. vivax and the recently reported resistant strains from Papua New Guinea.

Animals↗
PubMed1991

Molecular cloning and characterization of the acidic 80-kDa protein kinase C substrate from rat brain. Identification as a glycoprotein.

The complete amino acid sequence of 80 K, the major acidic protein kinase C (PKC) substrate of rat brain, was deduced from a cDNA nucleotide sequence. An open reading frame of 927 bases predicted a protein of 309 amino acid residues (Mr = 29,796, pI = 4.06). 58% of the deduced protein sequence was confirmed by Edman degradation of peptides generated by proteolysis of purified 80 K. The absence of internal methionine residues in the deduced amino acid sequence was confirmed by the inability to cleave 80 K with CNBr. Antiserum raised against a synthetic peptide corresponding to residues 298-309 of the predicted amino acid sequence recognizes the 80-kDa polypeptide in Western blots. The protein shows 65% sequence identity with a closely related PKC substrate from bovine brain. Genomic Southern blot analysis using a probe corresponding to a segment of the 80 K gene devoid of introns showed one major band. Northern blot analysis of rat brain RNA reveals a prominent transcript of 2.2 kilobases which hybridizes to 80 K cDNA. The amino acid composition and hydropathicity plot suggest an extended structure with no hydrophobic domains. The amino acid sequence showed many short repeats as well as several potential phosphorylation sites, five of which were for PKC, one was for both PKC and cyclic AMP-dependent protein kinase, and one for casein kinase II, and potential glycosylation sites. Indeed, carbohydrate moieties were detected on electroblots of purified 80 K using both a specific glycan stain and Galanthus nivalis plant lectin which binds to terminal D-mannose in the glycan moiety. This is the first time that this major PKC substrate has been identified as a glycoprotein.

Amino Acid Sequence↗
PubMed1991

Distribution of nerve growth factor receptor immunoreactivity in the human hippocampus.

Nerve growth factor (NGF) receptor-like immunoreactivity has been demonstrated in the normal adult human hippocampus, using minimally fixed cryostat sections obtained from snap-frozen tissue and incubated with the mouse monoclonal antibody, ME 20.4. The majority of the reactivity was associated with nerve fibre processes and their terminals. Numerous fibres were apparent in the alveus, originating from the fornix, and extending into the stratum oriens and pyramidal layer of the hippocampal formation. A more diffuse particulate reactivity, presumed to be nerve terminal, was observed around the pyramidal neurons and in the stratum radiatum, stratum lacunosum moleculare and also in the dentate fascia. The pattern of hippocampal NGF receptor immunoreactivity was broadly similar to acetylcholinesterase histochemical localization, indicating a principal localization on cholinergic axons innervating this area. Preliminary observations indicate an overall reduction in NGF receptor-immunoreactive axons and terminals in old age and Alzheimer's disease.

Acetylcholinesterase↗
PubMed1991

A complex chromosome rearrangement forms the BCR-ABL fusion gene in leukemic cells with a normal karyotype.

Chromosome in situ hybridization studies showed that the normal karyotype of leukemic cells from a patient with Ph1-negative, BCR-positive chronic myeloid leukemia (CML) concealed a complex t(9;22;20)(q34;q11;p13). The close association of 5'-BCR and 3'-ABL was demonstrated by field inversion gel electrophoresis, and in situ hybridization showed that BCR-ABL was located on the short arm of chromosome 20. Our findings further indicate that chromosome rearrangement is the cause of BCR-ABL gene fusion in leukemic cells that show a normal karyotype. Results from in situ hybridization studies were consistent with formation of the t(9;22;20) by a two step chromosomal rearrangement, but field inversion gel electrophoresis results indicated a more complex rearrangement.

Aged↗
PubMed1991

Non-ulcer dyspepsia.

This paper discusses the definition of non-ulcer dyspepsia and its relationship to other functional bowel disorders. The research on the prevalence, outcome, aetiology and management of this condition is reviewed with particular emphasis on its multifactorial nature. Future research will need to concentrate on the inter-relationship of physical and psychosocial factors including the health beliefs of the individual patient.

Dyspepsia↗
PubMed1991

Laterality and 5HT2 receptors in human brain.

Serotonin2 (5HT2) receptors were investigated in left and right frontal cortex of clinically and neuropathologically assessed controls. No significant difference in receptor binding between hemispheres was seen.

Aged↗
PubMed1990

Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity.

The mechanism by which T lymphocytes are tolerized to self or foreign antigens is still controversial. Clonal deletion is the major mechanism of tolerance for immature thymocytes; for mature T cells, tolerance is considered to reflect anergy rather than deletion, and to be a consequence of defective presentation of antigen. This paper documents a novel form of tolerance resulting when mature T cells encounter antigen in immunogenic form. Evidence is presented that exposure of mature T cells to Mlsa antigens in vivo leads to specific tolerance and disappearance of Mlsa-reactive V beta 6+ T cells. Surprisingly, the clonal elimination of V beta 6+ cells is preceded by marked expansion of these cells. Thus, tolerance induction can be the end result of a powerful immune response. These data raise important questions concerning the relationship of tolerance and memory.

Animals↗
PubMed1990

Rearrangement of the human ABL oncogene in a glioblastoma.

A number of protooncogenes have been implicated in human tumorigenesis. The ABL oncogene is consistently rearranged and activated as a consequence of the translocation t(9;22) that gives rise to the Philadelphia chromosome in chronic myeloid leukemia and in some cases of acute lymphoblastic leukemia. Here we describe rearrangement of ABL in a different type of malignancy. The glioblastoma cell line A172 lacks germline alleles of ABL. A recombination event, presumably followed by a duplication, has created two ABL alleles in which exon 11 is joined to chromosome 16 sequences. Although the main body of ABL exons was still present, two considerably shortened ABL mRNAs of 3.8 and 2.8 kilobases were detected; the 3.8-kilobase mRNA hybridized exclusively to an exon IB probe. Neither mRNA hybridized to an ABL probe encompassing part of the tyrosine kinase domain. Thus, the cell line A172 is able to survive in the absence of a functional ABL gene product, indicating that the role of ABL is unlikely to be "housekeeping."

Base Sequence↗