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G J Morgan

Publications and source records attributed to G J Morgan.

At least 109 records · Page 6Linked to original sources
PubMed1995

Genetic abnormalities during transition from Helicobacter-pylori-associated gastritis to low-grade MALToma.

The helicobacter-associated transition from chronic gastritis to MALToma (lymphoma of mucosa-associated lymphoid tissue) may require genetic change in the host. We have studied gastrectomy specimens from twelve cases of primary B-cell gastric lymphoma showing evidence of chronic gastritis and low-grade or high-grade MALToma to look for allele imbalance at microsatellites for six tumour-suppressor genes. We detected allelic imbalance at two of these loci (DCC in three, APC in two). In two DCC cases allele imbalance was seen in the transition from chronic gastritis to low-grade MALToma and in the third between low-grade and high-grade. Allele imbalance between chronic gastritis and low-grade MALToma is not necessarily causal in the transition. Rather, genetic change has occurred in the process of transformation.

Alleles↗
PubMed1995

Detection of clonal immunoglobulin gene rearrangements in the PBPC harvests of patients with acute lymphoblastic leukaemia.

We have used a fluorescently based PCR technique to detect rearrangements in the immunoglobulin heavy chain (IgH) gene in the presentation BM of five patients with adult ALL and have looked for similar rearrangements in their PBPC. Using this approach we have been able to demonstrate clonal rearrangements in the PBPC of two of five patients. Remission BM samples taken 6-12 weeks prior to leucapheresis failed to show a clonal rearrangement in either patient. The significance of these results is discussed.

Base Sequence↗
PubMed1993

Efficacy and safety of nabumetone versus diclofenac, naproxen, ibuprofen, and piroxicam in the elderly.

In a randomized, open-label, controlled, multicenter, 12-week study, the efficacy and safety of nabumetone (1,000-2,000 mg/day) versus diclofenac (100-200 mg/day), naproxen (500-1,500 mg/day), ibuprofen (1,200-3,200 mg/day), or piroxicam (10-20 mg/day) were evaluated in patients with osteoarthritis (OA) or rheumatoid arthritis (RA). The results in elderly patients (> or = 65 years of age) are presented. Nabumetone was as effective as the comparator nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of elderly OA and RA patients. Ibuprofen and diclofenac caused significantly (p < 0.05) more abdominal pain than nabumetone (8.5%, 13.1%, and 4.1%, respectively). The frequency of abdominal pain was dose related for all NSAIDs except nabumetone. Diarrhea was reported by significantly (p < 0.02) more nabumetone-treated (6.6%) than ibuprofen-treated (0.9%) elderly patients, but the incidence of diarrhea was not dose related. There were no clinically significant changes in renal function with nabumetone or the comparator NSAIDs. A significant change in hepatic enzymes occurred in elderly patients treated with diclofenac (3.3%), which was different than for patients treated with nabumetone (p < 0.04), naproxen (p < 0.06), or ibuprofen (p < 0.06). With regard to withdrawals for adverse events, more (p < 0.04) piroxicam-treated patients (4.9%) withdrew than nabumetone-treated patients (1%). In addition, doubling the dose of nabumetone from 1,000 mg/day to 2,000 mg/day did not result in a proportional increase in adverse events. However, with the comparator NSAIDs, proportional increases in adverse events occurred with increased dose. Finally, the efficacy and safety of nabumetone in elderly patients were similar to the efficacy and safety observed in nonelderly patients.

Aged↗
PubMed1993

Clinical features, diagnosis, and prognosis in rheumatoid arthritis.

The past year has witnessed a modest expansion in our understanding of the clinical, diagnostic, and prognostic features of rheumatoid arthritis. Almost every continent has reported prevalence, phenotype, and clinical features of rheumatoid arthritis subpopulations. Reviews of the natural history and therapy of cervical spine disease, Felty's disease, and lung involvement dominate the clinical literature. Rheumatoid arthritis-like syndromes have been reported to occur after immunotherapy with interferon alfa and interleukin-2. There have been case studies on human immunodeficiency virus, cachexia, pregnancy, "pseudosepsis," bone loss, and malignancy in rheumatoid arthritis. Diagnostic criteria and new classifications for functional and global impairment have been published, and new health impairment questionnaires have been evaluated. Novel isotopes and the role of magnetic resonance imaging in damaged joints were discussed. Rheumatoid factor was reaffirmed as a significant prognostic variable, and the roles of immunogenetic loci, sulfur oxidation, and serum matrix proteins were evaluated in early rheumatoid arthritis. Functional status was again verified as a strong prognostic marker.

Arthritis, Rheumatoid↗
PubMed1992

Breakpoints at 11q23 in infant leukemias with the t(11;19)(q23;p13) are clustered.

We have analyzed a series of nine infant leukemias that carry a t(11;19)(q23;p13). They had the morphologic features of acute lymphoblastic leukemia (ALL) and expressed markers typical of B-cell progenitor ALL or pre-B ALL; one coexpressed myeloid markers in addition to lymphoid markers (biphenotypic). Two probes (P/S4 and 98.40) subcloned from a yeast artificial chromosome (YAC) known to span the breakpoint in the t(4;11) were used to investigate DNA isolated from the leukemic cells of these patients. A total of approximately 15 kb of genomic DNA in the vicinity of the probes was examined by conventional Southern blot analysis using a series of restriction enzymes. In eight of the nine cases, the breakpoint could be mapped to an approximately 10-kb BamHI fragment disclosed by hybridization to the P/S4 probe.

Antigens, CD↗
PubMed1992

Inversion of chromosome 16 with the Philadelphia chromosome in acute myelomonocytic leukemia with eosinophilia. Report of two cases.

Two cases are described with the rare combination of inv(16)(p13q22), strongly associated with acute myelomonocytic leukemia with eosinophilia, M4Eo, and the Philadelphia translocation, t(9;22)(q34;q11), hallmark of chronic myeloid leukemia (CML) and rarely found, (less than 1%), in acute nonlymphocytic leukemia. The patients were: case 1, a 9-year-old girl presenting with a white blood cell count (WBC) 42 x 10(9)/L with 32% blasts and bone marrow with blasts and eosinophil precursors consistent with M4Eo, and case 2, a 25-year-old man with WBC 34.7 x 10(9)/L with 13% blasts and bone marrow with features of M4Eo and basophilia. Both patients achieved remission but died following bone marrow transplantation in first remission (case 1) or in relapse (case 2). Cytogenetic findings were: case 1, at diagnosis, 46,XX,inv(16)(p13q22)(21)/46,XX,t(9;22) (q34;q11),inv(16)(8)/46,XX(10), and case 2, at diagnosis, 46,XY,t(9;22) (q34;q11),inv(16)(p13q22) (16) and in remission, 46,XY,t(9;22)(q34;q11) (1)/46,XY (24). Investigation of the breakpoint on 22 in case 1 with Southern blotting and the polymerase chain reaction demonstrated the presence of a p190 mRNA and a breakpoint typical of acute leukemia. Thus a diagnosis of M4Eo was supported by clinical and cytogenetic sequelae in each case; the Ph in case 1 was apparently secondary to inv(16), in case 2 the Ph probably preceded inv(16) in the etiology of the leukemia.

Adult↗
PubMed1992

How are cancer associated genes activated or inactivated?

Altered behaviour or the transformation of a cell can result from the abnormal expression of some oncogene products. Elevated or inappropriate expression can result from (i) mutations in the regulatory region of the gene, (ii) aberrant expression of a transcription factor involved in the regulation of the gene, (iii) gene amplification, or (iv) the insertion of a viral promoter upstream of the gene. In addition, an alteration in the product of a proto-oncogene can lead to the acquisition of a transforming activity. Such changes have been shown to include (i) point mutation, (ii) deletion, and (iii) the formation of fusion genes. Finally, the loss of activity of a gene product can contribute to transformation. This can come about by (i) small or large deletions, (ii) point mutations which abolish function or expression of an intact protein, or (iii) mutations which lead to a protein with an activity which can inhibit the suppressor activity of the normal allele.

Gene Expression Regulation, Neoplastic↗
PubMed1992

Philadelphia chromosome-positive leukaemia: the translocated genes and their gene products.

Overwhelming evidence indicates a role for the deregulated ABL protein tyrosine kinase in the aetiology of CML and Ph-positive acute leukaemia. These disorders are characterized by the generation of BCR/ABL fusion proteins with elevated tyrosine kinase activity. Although much is known concerning the transforming potential of ABL proteins in various systems, very little is understood of the normal function and mode of regulation of ABL activity. The mechanism of oncogenic activation is therefore also obscure. In spite of this, our understanding of the molecular details of these chromosomal translocations allows the design of therapies directed against their unique, leukaemia-specific proteins and RNA products.

Abelson murine leukemia virus↗
PubMed1992

A phospholipid-beta 2-glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection.

Anticardiolipin antibodies (aCL) purified from patients with autoimmune disease have recently been shown to interact with a phospholipid-binding plasma protein, beta 2-glycoprotein I (beta 2-GPI). The aim of this study was to determine whether aCL purified from patients with infection also interact with beta 2-GPI. aCL purified from 23 patients with malaria, infectious mononucleosis, tuberculosis, hepatitis A or syphilis did not require the presence of beta 2-GPI to bind cardiolipin (CL). In contrast, aCL were purified from 11 out of 12 patients with autoimmune disease that bound CL only in the presence of beta 2-GPI. Thrombotic complications appear to be associated with aCL occurring in autoimmune disease but not with aCL associated with infections. We postulate that this increased risk of thrombosis in the autoimmune group may be due to the presence of aCL that bind CL in association with beta 2-GPI, a plasma protein with anticoagulant activity.

Antibodies, Anticardiolipin↗
PubMed1992

Concordance between clinician and patient assessment of physical and mental health status.

The degree of concordance between clinicians' and patients' assessment of the patient's physical and mental functioning was examined in 166 consecutive eligible outpatients with rheumatoid arthritis (RA) using 4-category ordinal scales. The weighted kappa statistic was 0.39 for physical functioning and 0.30 for mental functioning, both indicating a fair degree of concordance. This disagreement differed in magnitude and direction depending on the level of disability present. We conclude that clinicians and their patients with RA often disagree in their assessment of the degree of physical and mental impairment that the patient experiences. These disagreements demonstrate the need for formal assessments of outcome and should be recognized and resolved when managing individual patients.

Adolescent↗
PubMed1991

Detection of residual leukemia after bone marrow transplant for chronic myeloid leukemia: role of polymerase chain reaction in predicting relapse.

We used the polymerase chain reaction (PCR) to detect residual leukemia-specific mRNA in blood and marrow from 37 patients in complete hematologic and cytogenetic remission after allogeneic bone marrow transplant (BMT) for chronic myeloid leukemia (CML). Our two-step PCR method involved the use of "nested primers" in the second step and could detect one K562 cell diluted into 10(5) normal cells. Elaborate measures were taken to exclude false-positive and false-negative results. In nine patients whose blood and marrow were studied simultaneously the results were concordant (two positive and seven negative). Twenty-three patients transplanted in chronic phase (CP) with unmanipulated donor marrow were studied. Blood cells from nine of these patients were studied 3 to 6 months post-BMT and six were PCR positive; three were negative on subsequent studies. Blood cells from 18 patients studied between 8 months and 8 years post-BMT were all PCR negative. Nine patients transplanted in CP with T-cell-depleted marrow cells were studied. Blood from five was positive 3 to 24 months post-BMT; blood from five was negative 3 to 6 years post-BMT. Four patients no longer in first CP were studied after BMT with unmanipulated donor marrow. Blood from all four was positive 5 to 19 months post-BMT. Based on the known clinical results of transplant in these three cohorts we conclude that PCR may be positive within 6 months of BMT in patients who can expect long-lasting remission, whereas PCR positivity later after BMT may indicate that the probability of cure is reduced. Thus, the technique may prove useful for early assessment of new transplant protocols that might inadvertently increase the risk of relapse.

Base Sequence↗
PubMed1990

The role of alternative splicing patterns of BCR/ABL transcripts in the generation of the blast crisis of chronic myeloid leukaemia.

Three major types of mRNA can be expressed as a result of the Philadelphia translocation, dependent on the position of the break within the BCR gene on chromosome 22. In addition, alternative splicing of the mRNA transcribed from the BCR/ABL fusion gene has been reported and it has been suggested that this may play a role in the generation of the acute phase of Philadelphia positive chronic myeloid leukaemia (CML). We have examined the fusion RNA present in 24 cases of chronic phase CML and 21 cases of patients with CML in blast crisis using the polymerase chain reaction. In no case was it possible to detect the presence of the e1a2 junction which encodes the p190 hybrid protein product. We conclude that the acquisition of the p190 does not play a significant role in the generation of the blast crisis of CML. Neither could we detect a significant difference in the number of cases which simultaneously express both b2a2 and b3a2 junction products in samples isolated from chronic phase and blast crisis. In the series analysed by ethidium bromide stained gels, there was, however, an increase in the percentage of cases expressing the b3a2 junction in the mononuclear cells of blast crisis patients as compared to the white blood cells of patients in chronic phase.

Base Sequence↗