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Biomedical subjects

C Morris

Publications and source records attributed to C Morris.

At least 91 records · Page 5Linked to original sources
PubMed1998

Inflammatory potential of C-reactive protein complexes compared to immune complexes.

C-reactive protein (CRP) is an acute phase serum protein that binds to phosphocholine (PC) and to components of damaged tissue. CRP resembles antibody in that it binds to ligands and activates the classical complement pathway. To compare the processing of CRP complexes to that of IgG complexes, we have prepared complexes containing the same ligand, PC-conjugated BSA, and IgG antibody to either BSA or CRP. We previously demonstrated similar complement-mediated binding of these complexes to erythrocyte complement receptors. CRP and IgG also bind to receptors on neutrophils (PMN), providing another possible pathway for clearance of ligands. PMN binding of IgG complexes can lead to activation with damaging inflammatory consequences. In the present report we have used CRP and IgG complexes containing PC-BSA to compare binding to PMN and activation of PMN adherence to endothelial cells. The results indicate that CRP complexes do not activate PMN whereas IgG complexes do. Binding assays indicate that there is substantially greater binding of IgG than CRP complexes to PMN.

Animals↗
PubMed1998

Protection by ebselen against cisplatin-induced nephrotoxicity: antioxidant system.

This study was designed to investigate the cisplatin-induced alteration in renal antioxidant system and the nephroprotection with ebselen. Male Wistar rats were injected with (1) vehicle control; (2) cisplatin; (3) ebselen; and (4) cisplatin plus ebselen. Rats were sacrificed three days post-treatment and plasma as well as kidney were isolated and analyzed. Plasma creatinine increased 598% following cisplatin administration alone which decreased by 158% with ebselen pretreatment. Cisplatin-treated rats showed a depletion of renal glutathione (GSH) levels (52% of control), while cisplatin plus ebselen injected rats had GSH values close to the controls. Antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities decreased 38, 75 and 62% of control, respectively, and malondialdehyde (MDA) levels increased 174% of control following cisplatin administration, which were restored to control levels after ebselen treatment. The renal platinum level did not significantly change with ebselen pretreatment. This study suggests that the protection offered by ebselen against cisplatin-induced nephrotoxicity is partly related to the sparing of antioxidant system.

Animals↗
PubMed1998

O6-methylguanine-DNA methyltransferase in pretreatment tumour biopsies as a predictor of response to temozolomide in melanoma.

Resistance of tumour cells to methylating and monochloroethylating agents in vitro and in vivo has been linked to levels of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). In a clinical trial of temozolomide in advanced malignant melanoma, the relationship between pretreatment MGMT levels in biopsies of cutaneous tumours and involved lymph nodes and clinical response to the drug has been studied. Among 50 evaluable patients, there were three complete responses (CR), four partial responses (PR), six with stable disease (SD) and 37 with progressive disease (PD), with an overall response rate of 14%. In 33 patients in whom MGMT level and clinical response could be evaluated, the tumour MGMT levels (fmol mg(-1) protein) were: CR, 158 +/- 119; PR, 607 +/- 481; NC, 171 +/- 101; PD, 185 +/- 42.3. Thus, measurements of pretreatment levels of MGMT in melanoma did not predict for response to temozolomide.

Adult↗
PubMed1998

Identification of multiple forms of 180-kDa ribosome receptor in human cells.

Herein, we describe the analysis and mapping of cDNA clones encoding variant forms of the human homolog of the canine 180-kDa ribosome receptor (p180). One form, similar to the chicken ES/130 homolog, possesses a large uninterrupted C-terminal region composed predominantly of heptad repeats predicted to form an alpha-helical double-stranded coiled-coil rod. Other forms contain in addition a 10-amino acid consensus motif, NQGKKAEGAQ, repeated up to 54 times in tandem close to the N-terminus. Such repeats in canine p180 represent a ribosome-binding domain. The cDNA hybridized to a major 6-kb transcript in all tissues examined, where very high expression was observed in tissues that carry out a high level of secretion such as pancreas, liver, and placenta. The ES130/p180 gene was mapped to chromosome 20p12, and a potential pseudogene appears to reside on chromosome 7. In summary, the data suggest that p180 exists in humans in different forms because of complete removal of tandem repeats, or partial intraexonic splicing, creating different repeat lengths with potentially novel ribosome-binding characteristics.

Alternative Splicing↗
PubMed1998

Autologous vein-covered stent repair of a cervical internal carotid artery pseudoaneurysm: technical case report.

OBJECTIVE AND IMPORTANCE: Stenting of a cervical internal carotid pseudoaneurysm is presented using a stent covered with saphenous vein. This procedure resulted in immediate exclusion of the aneurysm and maintained patency of the carotid artery. CLINICAL PRESENTATION: A gunshot to the neck resulted in airway obstruction and respiratory arrest with neurological injury in a male patient. Angiographic investigation revealed an enlarging cervical internal carotid pseudoaneurysm, possibly the source of a cerebral embolism. Anticoagulation had to be stopped because of bleeding complications. A decision was made to conduct definitive percutaneous treatment of the pseudoaneurysm. TECHNIQUE: A Palmaz stent (JJIS, Warren, NJ) was covered with saphenous vein harvested from the patient's leg. Using standard technique and a simple innovation for stent construct introduction into the sheath, the vein-covered stent was placed across the opening of the aneurysm and dilated into position with a balloon. CONCLUSION: Immediate exclusion of a cervical internal carotid pseudoaneurysm was performed using an autologous vein-covered stent. One-month follow-up confirmed continued exclusion of the pseudoaneurysm and carotid patency without stenosis.

Adult↗
PubMed1998

Immunohistochemical investigation of evolving inflammation in lesions of acne vulgaris.

The mechanisms involved in the development of inflammation in acne vulgaris have yet to be elucidated. Previous studies have shown that the initial cellular infiltrate in early inflammatory lesions is mononuclear, predominantly CD4 positive T cells. The aims of this study were to investigate the pattern of expression of adhesion molecules and HLA-DR in evolving acne lesions. Forty-nine patients with moderate to severe acne were biopsied following lesion mapping. Lesions were classified according to their duration of inflammation as up to 6 h, from 6 to 24 h, from 24 to 48 h and from 48 to 72 h. The cellular infiltrate was determined using monoclonal antibodies to CDI, CD3, CD4 and CD8. The expression of ICAM-1, E-selectin. VCAM-1 and HLA-DR was determined. Early (6 h) lesions had perivascular CD3 positive T-cell infiltrates which were predominantly CD4 positive. This was associated with vascular expression of ICAM-1, E-selectin, VCAM-1 and HLA-DR. Periductal infiltrates were present in 70% of the early lesions (up to 6 h). The cells were predominantly CD4 positive and associated with a high level of HLA-DR and ICAM-1 expression. Periductal infiltration increased with time and persisted to 72 h. ICAM-1 and HLA-DR were expressed epidermally in early and late lesions. CD1 positive cells were a minor, but consistent element in the perivascular and periductal infiltrates of early and late lesions. There was no statistically significant difference in the levels of expression of E-selectin, VCAM-1, ICAM-1 or HLA-DR for lesions of different duration. The pattern of HLA-DR and adhesion molecule expression plus the nature of the cellular infiltrate supports the hypothesis that inflammation in acne is mediated by CD4 positive T cells.

Acne Vulgaris↗
PubMed1998

The hidden determiner of student learning opportunity on clinical placement.

A qualitative study was undertaken to gain deeper insight into the nature of learning opportunities afforded to speech and language therapy (SLT) students on clinical placement. The study aimed to illuminate aspects of the placement learning environment that have a positive or negative influence. Indepth interviews were conducted with two groups of students (13 in total), five education-based clinical tutors and five National Health Service (NHS)-based clinical supervisors. Interviews were transcribed, indexed, charted and analysed. A previously unexplored theme emerged from the data--that of risk. This paper explores the concept of risk and looks at the ways in which risk defines the amount, timing and nature of clinical experience for students.

Humans↗
PubMed1998

Exploring the crisis in clinical training: looking to the future.

How can the crisis in training be understood? How can it be resolved? A context for this paper is provided in terms of relevant professional and educational policy. A critical review of nationally available data is presented. It will be argued that commonly cited reasons for not offering student placements might have obfuscated underlying dynamics, which are related to the model of education adopted in the United Kingdom. It will be argued that a shift in emphasis in initial and continuing professional education is relevant.

Forecasting↗
PubMed1997

Molecular cloning, nucleotide sequence, and function of a site-specific recombinase encoded in the major 'pathogenicity island' of Salmonella typhi.

The genome of the typhoid fever bacterium, Salmonella typhi, contains at least three large insertions ('pathogenicity islands') relative to the chromosome of Salmonella typhimurium (which is normally non-invasive for humans) [Liu, S.-L., Sanderson, K.E., 1995. Rearrangements in the genome of the bacterium Salmonella typhi. Proc. Natl. Acad. Sci. USA 92, 1018-1022]. DNA encoding a site-specific recombinase (the rci gene) and an adjacent putative pilus-tip adhesin protein (the pilV gene) was located (near min 94) in the major 'pathogenicity island' of the S. typhi chromosome, cloned, and sequenced. It was shown that the Rci protein inverted a DNA segment of 490 bp, between two 19-bp inverted repeat elements, to place either of two possible C-termini on a constant N-terminal region of the PilV protein. Both possible PilV proteins were seen when the alternative pilV genes were transcribed from the T7 promoter and translated in vivo. Both the rci and the N-terminal region of the pilV gene show a high degree of homology to genes encoded by the IncI2 plasmid R721 and the IncI1 plasmid R64. One of the possible pilV C-termini (in the pilV1 gene) is highly homologous to shufflon C (one of the possible PilV C-termini) of R64; the other possible pilV C-terminus (in the pilV2 gene) shows no homology to any published shufflon. In the R64 plasmid, the PilV proteins are pilus-tip adhesins; different PilV proteins recognize different potential recipient bacterial strains as a prelude to mating in liquid culture [Komano, T., Kim, S.-R., Yoshida, T., Nisioka, T., 1994. DNA rearrangement of the shufflon determines recipient specificity in liquid mating of IncI1 plasmid R64. J. Mol. Biol. 243, 6-9]. It is likely that S. typhi encodes pili bearing two alternative PilV proteins as tip adhesins, one of which recognizes, specifically, a membrane component of Escherichia coli K-12, while the specificity of the other PilV protein is not known.

Amino Acid Sequence↗
PubMed1997

HLA-DR antigens associated with major genetic risk for late-onset Alzheimer's disease.

Hla-dr antigen types were determined from DNA isolated from post-mortem brain tissue of age-matched groups of 78 patients with pathologically confirmed late-onset Alzheimer's disease (AD) and 50 controls. The results suggest that for individuals with no apolipoprotein E epsilon 4 alleles the presence of either DR1, 2 or 3 antigens is associated with a significantly increased risk for development of late-onset AD. Conversely the DR4 or 6 antigens are associated with a decreased risk of similar magnitude. This DR effect, rather than prolonged use of non-steroidal anti-inflammatory drugs, could be responsible for the reported lower prevalence of AD in rheumatoid arthritis (a condition associated with an increased frequency of DR-4).

Age of Onset↗
PubMed1997

Isolation of diabetes-associated kidney genes using differential display.

Differential Display was used to isolate genes that show transcriptional changes in the kidney during the development of diabetes in the GK rat. Eight candidate diabetes-associated cDNA fragments, CDK1-8, were isolated and characterised. cDNA sequencing and subsequent database analysis revealed that CDK2, 4, 5 and 6 showed no significant sequence similarity to previously reported genes, suggesting that they represent novel genes, whereas CDK 1, 3, 7 and 8 showed significant similarity with rat lactate dehydrogenase, rat amiloride sensitive sodium channel, EST109013 and mouse ubiquitin-like protein respectively. The differential mRNA expression of CDK1-8 was confirmed using differential screening of slot blots. CDK1, 2, 4 and 8 mRNAs appeared to increase whereas CDK3, 5, 6 and 7 mRNAs decreased in the kidneys of GK rats with increasing hyperglycaemia. The altered renal mRNA expression of these genes in association with increased hyperglycemia in the GK rat suggest that they are candidates for a role in the development of diabetic nephropathy.

Animals↗
PubMed1997

Comparative genomic hybridization reveals previously undescribed amplifications and deletions in the chronic myeloid leukemia-derived K-562 cell line.

We used comparative genomic hybridization (CGH) to identify a number of previously undescribed chromosomal imbalances in K-562, a spontaneously transformed cell line originally derived from leukemic cells of a chronic myeloid leukemia (CML) patient in blast crisis. Noteworthy were a discrete amplification in band 13q31, increased copy number of chromosome arms 1q, 5p, 6p, and 16q, and loss of material from 8p, 9p, 10q, and 17p. Amplification within bands 9q34 and 22q11.2 was consistent with previous descriptions of increased copy number of the CML-specific 5'BCR-3'ABL fusion gene in K-562. However, amplification of a large distal segment, 9q31-->9q34, mostly proximal to the ABL locus, was unexpected and is unlikely to be related to BCR-ABL recombination. Previous karyotype studies are reviewed in detail and compared with the CGH findings.

Female↗
PubMed1997

Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia.

Antibody-mediated autoimmunity underlies a diverse range of disorders, particularly in the nervous system where the extracellular domains of ion channels and receptors are especially vulnerable targets. We present here a novel means of detecting autoantibodies where the genes of the suspected target proteins are known, and use it to detect specific autoantibodies in acquired neuromyotonia (Isaacs' syndrome), a disorder characterized by hyperexcitable motor nerves and sometimes by central abnormalities. We expressed different human brain voltage-gated potassium channels in Xenopus oocytes by injecting the relevant alpha-subunit complementary RNA, and detected antibody binding by immunohistochemistry on frozen sections. Antibodies were detected to one or more human brain voltage-gated potassium channel in 12 of 12 neuromyotonia patients and none of 18 control subjects. The results establish neuromyotonia as a new antibody-mediated channelopathy and indicate the investigative potential of this molecular immunohistochemical assay.

Autoantibodies↗
PubMed1997

Klinefelter syndrome and non-Hodgkin lymphoma.

Patients with a 47,XXY karyotype (Klinefelter syndrome) appear to have an increased risk of developing cancer, especially male breast cancer and germ cell tumors, but rarely malignant hematologic disorders. We report a patient with a low grade B-cell non-Hodgkin lymphoma with a 47,XXY karyotype in both the tumor and constitutional cells. This is only the 13th reported case of malignant lymphoma in a patient with Klinefelter syndrome. Although some authors postulate that the 47,XXY karyotype may be a predisposing factor in the development of hematological malignancies, the lack of reported cases suggests that such associations may be no more than chance findings.

Aged↗