Search PubMed⌕ Search

Biomedical subjects

A G Morris

Publications and source records attributed to A G Morris.

At least 37 records · Page 2Linked to original sources
PubMed1998

Dental mutilation in southern African history and prehistory with special reference to the "Cape Flats Smile".

Southern Africa has a long history of dental mutilation in the form of dental chipping and of intentional removal of anterior teeth. The first evidence is found in the skeletons of Early Iron Age populations (ca. 1500 years before present), but the incidence decreases in archaeological sites of more recent origin. In modern times, dental mutilation appears to have been limited to the people of the countries further north in Africa, but the one exception is the presence of deliberate incisor removal amongst the communities of the Western Cape. It is hypothesised in this paper that the modern practice in the Cape is associated with youthful gangs in the poorer communities, and acts as part of a rite of passage into adulthood. The "socio-sexual" theory, as reflected in such names as the "passion gap", is shown to be both wrong and insulting. The name "Cape Flats Smile" is recommended as a more appropriate and respectful term for the phenomenon.

Adolescent↗
PubMed1997

The number of triplet repeats in five brain-expressed loci with CAG repeats is not associated with schizophrenia.

We have previously shown that large expansions of CAG (CTG) triplets are associated both with schizophrenia itself and with an early age-at-onset of the disease. However, the repeat expansion detection (RED) method used did not provide a chromosomal location for the expanded region(s) (Morris et al., 1995). In a further study of our schizophrenic and control patients, we have now examined the length of the repeated sequence in five loci that are expressed in brain and are known to contain CAG repeat regions (Li et al., 1993). No enlarged repeat regions were identified; it is unlikely therefore that expansions at any of these five loci can account for expansions of up to 136 triplets identified by the RED method.

Age of Onset↗
PubMed1997

Characterisation of the ultraviolet-sensitive opsin gene in the honey bee, Apis mellifera.

The cDNA sequence of the ultraviolet-sensitive opsin in the honey-bee, Apis mellifera, with associated 5' and 3' untranslated regions, is presented. The analysis of genomic structure reveals seven introns in the coding region of the gene, with six at novel positions for an insect opsin gene. The equivalent site to the counterion in vertebrate opsins is occupied by a Tyr residue. This contrasts with the presence of Phe at this site in the ultraviolet-sensitive opsins of Drosophila sps. A comparison of the amino acid sequence within the seven alpha-helical transmembrane regions of insect ultraviolet/blue-sensitive opsins identifies substitution at five sites that involve either replacement of a polar with a non-polar residue, or a change in charge. Such changes are known to result in spectral shifts in vertebrate pigments. Phylogenetic analysis indicates that the ultraviolet-sensitive pigments represent an ancient class of insect opsins.

Amino Acid Sequence↗
PubMed1997

Clinical significance of selective decline of donor-reactive IL-2-producing T lymphocytes after renal transplantation.

Limiting dilution analysis technique was used to enumerate the circulating precursor frequency of donor and third-party-reactive helper T lymphocytes (HTLpf) in 28 renal allograft recipients before (pre-tx) and at three intervals (T1: 60-90 days, T2: 120-180 days, T3: 360-1620 days) after transplantation (post-tx). Two patterns of responses were identified, in group 1 (n = 12), a five to 31-fold reduction of donor-reactive HTLpf (ranging from 1/19231-1/62500) occurred within 90-1620 days post-tx, while in group 2(n = 16), no significant changes of donor-reactive HTLpf were seen. In both groups, the third-party-reactive HTLpf in most of these patients remained largely unchanged throughout the study period. The number of HLA-DR mismatches, total number of rejection episodes, serum creatinine levels, and biopsy findings at T3 were compared in both groups using Fisher's exact probability, and the Mann-Whitney test. We found that 11 patients (92%) in group 1 were HLA-DR compatible with donors, while nine (56%) patients in group 2 were HLA-DR compatible with donors, p = 0.04. In group 1 eight rejection episodes occurred in five (41.6%) patients during the study period, compared to 33 in 13 (81%) patients in group 2, p = 0.03. Group 1 had a significantly lower serum creatinine level (at T3); median: 136 vs 165 mumol/l for group 2, p = 0.03. Biopsy indicated no rejection (at T3) in eight (66%) patients in group 1 as compared to three (18%) patients in group 2, p = 0.03. Taken together, these results indicate that the frequency of circulating HTLpf correlate with the clinical status of the graft. Therefore monitoring of HTLpf in the peripheral blood could be useful in predicting graft outcome and selecting patients for reducing immunosuppression.

Adolescent↗
PubMed1997

Five newly established oesophageal carcinoma cell lines: phenotypic and immunological characterization.

The derivation of permanent cell lines from 40 resected oesophageal carcinomas has been attempted. Five long-term lines have been established from three adenocarcinomas, one mixed carcinoma and one squamous carcinoma. Molecular and cellular analyses have been carried out on the lines and clones derived from them. Karyotype analysis indicates genetic variation among the clones. HLA-A, -B and -C is expressed constitutively, but not HLA-DR. ICAM-1-expressing phenotypes may have arisen during adaptation to long-term culture. All lines are capable of response to interferon-gamma (IFN-gamma) and all produce transforming growth factor beta 1 (TGF-beta 1). Two lines are resistant to the inhibitory growth effects of the latter, possibly contributing to malignancy. It is anticipated that these lines, originating from histologically different carcinomas, will provide a valuable, continuous resource for the investigation and treatment of these aggressive tumours.

Animals↗
PubMed1997

Steroid withdrawal and donor-specific hyporeactivity after cadaveric renal allotransplantation on maintenance triple therapy.

BACKGROUND: Even in low doses, long-term steroid immunosuppression is known to cause serious complications. However, the safety of steroid withdrawal has not been proven in randomized clinical trials. This study examines donor-specific hyporesponsive transplant recipients before and after steroid withdrawal, to see if reduction in immunosuppression was associated with consistent changes in antidonor immunological reactivity. METHODS: Using limiting dilution assays, the circulating precursor frequency of donor and third-party-reactive helper T lymphocytes (HTLpf) were determined in 21 consecutive cadaveric renal allograft recipients on standard triple therapy, before (pre-tx) and at different time points after transplantation (post-tx). Patients were selected for steroid withdrawal by clinical criteria (stable graft function and no or only one very mild rejection episode). RESULTS: Of 21 patients studied, steroids were successfully withdrawn in nine (steroid withdrawn group, SWG) for at least 187 days (mean: 380 +/- 168.5), and were not withdrawn in 12 patients (steroid continued group, SCG). In the SWG seven of nine patients developed at least fivefold reduction of post-tx donor-reactive HTLpf (range 5-17), relative to pre-tx, as compared to two of twelve patients in the SCG, P = 0.01. In both groups, the third-party-reactive HTLpf in most of these patients remained largely unchanged throughout the study period. In the SWG, no significant difference of serum creatinine level was found before and at 6 months after steroid withdrawal (mean: 138 +/- 24 versus 132 +/- 40, P = 0.45). CONCLUSION: Patients who developed donor-specific hyporeactivity as evidenced by low donor-reactive HTLpf had stable graft function and stable HTLpf levels after complete steroid withdrawal.

Adult↗
PubMed1997

Exclusion of CAG repeat expansion as the cause of disease in autosomal dominant retinitis pigmentosa families.

The involvement of genes with expanded tracts of (CAG)n in some neurodegenerative diseases is well established. Whether genes containing these motifs could also have a role in degenerative diseases affecting the retina, which is also neural in origin, is unknown. We investigated (CAG)n expansions as a cause of disease in a panel of eight autosomal dominant retinitis pigmentosa (ADRP) pedigrees, including families known to map to the RP9, RP11, and RP13 loci, using the technique known as "repeat expansion detection" (RED). An expansion was detected in one of the unlinked families, but it did not segregate with the disease and was thus nonpathogenic. Expansions were not detected in any other families. In conclusion, expanded (CAG)n repeats are not the cause of disease in the families we have studied, but given the high level of heterogeneity in RP and in retinal degenerations in general they remain strong candidates for involvement in other forms of retinal dystrophy.

Female↗
PubMed1997

Expression of CD44 splice variants in colorectal cancer.

BACKGROUND: The CD44 gene codes for a family of heavily glycosylated cell surface proteins that have been linked with tumour metastasis. The aim of the study was to analyse the expression of CD44 messenger RNA in colorectal cancer. METHODS: The expression of CD44 variants 2 and 7 in colorectal tumour samples was compared with that in normal colon and lymphocytes from 59 patients using reverse transcription-polymerase chain reaction followed by blot hybridization with exon-specific probes, and a nested polymerase chain reaction. RESULTS: All samples of tumour and metastatic tissue showed complex overexpression of many alternatively spliced products of the CD44 gene. Normal colon, liver and lymphocytes predominantly expressed the standard form of the CD44 molecule (CD44S) with low levels of two or three variants hybridizing to exons v2 and v7. CONCLUSION: Deranged CD44 gene activity in colorectal cancer cells is confirmed. The analysis of CD44 gene expression may provide a promising marker for the early detection of colonic tumours.

Aged↗
PubMed1997

Detection of circulating tumour cells and nodal metastasis by reverse transcriptase-polymerase chain reaction technique.

BACKGROUND: In the search for occult metastases in lymph nodes or circulating tumour cells, a reverse transcriptase-polymerase chain reaction (RT-PCR) assay was developed to detect tumour-specific splice variants of the transcript of the CD44 gene. The assay was highly sensitive and could detect ten tumour cell per 10(5) leucocytes. METHODS: RNA was purified from peripheral blood (n = 24) and regional lymph nodes (n = 14) from patients with colorectal cancer. Complementary DNA was made and amplified using primers specific for the CD44 gene. Southern blotting with exon-specific probes was used to enhance the sensitivity. RESULTS: Tumour cells were detected in peripheral blood samples in four patients and lymph nodes in nine, in one of whom conventional histology had not detected tumour cells. CONCLUSION: This technique may be useful in the early diagnosis of primary or metastatic tumours, in assessing prognosis and in detecting residual disease after treatment.

Aged↗
PubMed1996

Accessory cell requirements for T lymphocyte activation and interferon-gamma production in peripheral lymph nodes.

Allergen-activated draining lymph node cells (LNC) isolated from mice exposed topically to the contact allergen oxazolone mount vigorous proliferative responses and secrete substantial amounts of interferon-gamma (IFN-gamma) when cultured with the T lymphocyte mitogen concanavalin A (con A). In contrast, although naive LNC prepared from untreated mice display con A-driven proliferative responses of comparable magnitude, they produce only very low levels of IFN-gamma. Secretion of IFN-gamma by con A-stimulated naive LNC was augmented significantly by the addition to culture of a small number of syngeneic dendritic cells (DC), under conditions where there was no influence on the vigour of proliferative responses and where the exogenous DC themselves failed to produce IFN-gamma. Augmentation of IFN-gamma production was not observed when exogenous populations depleted of DC were added to culture. It is proposed that discrete aspects of the primary activation of naive T lymphocytes display differential requirements for accessory cells and that the development of IFN-gamma producing cells necessitates sufficient numbers of dendritic cells.

Animals↗
PubMed1996

The exfoliation of free malignant cells in the peritoneal cavity during resection of colorectal cancer.

The presence of free malignant cells in the peritoneal cavity following potentially curative resection of colorectal cancer may be responsible for some cases of local recurrence. Twenty-six patients (age 58-88 years, male:female 12:14) undergoing colorectal cancer surgery were studied to determine frequency of occurrence of tumour cells in the peritoneal cavity using an immuno-magnetic cell separation technique. Peritoneal washings were collected after opening the peritoneal cavity and also prior to closure. A murine monoclonal antibody specific for epithelial cells was added to the peritoneal washings followed by magnetic labelled goat-antimouse antibody. The labelled tumour cells were retrieved by passing through the magnetic activated cell sorter (MACS). Tumour cells were detected in peritoneal washings from 11 patients (preresection only n = 0, post-resection only n = 6, and both n = 5). Five of these 11 patients had potentially curative surgery. This study supports the use of MACS in detecting free malignant cells in the peritoneal cavity.

Aged↗
PubMed1996

Susceptibility of AML cells to in vitro apoptosis correlates with heat shock protein 70 (hsp 70) expression.

Acute myeloid leukaemia (AML) cells from some individuals rapidly undergo apoptosis during in vitro culture. We have analysed this mode of cell death in AML cells harvested from patients at initial presentation and during subsequent treatment/relapse. Using flow cytometric analysis of propidium iodide-stained cells and quantitation of the subdiploid apoptotic peak, we observed that leukaemic cells from patients with AML displayed a heterogenous susceptibility to apoptosis in terms of the rate of accumulation of apoptotic cells. After 48 h incubation in the absence of added serum or exogenous growth factors the percentage of apoptotic cells ranged from 3% to 99%. This susceptibility to apoptosis correlated significantly with intracellular expression of hsp70 (P = 0.009), but not hsp90, and was also associated with the presence of p53 and low levels of expression of bcl-2.

Acute Disease↗
PubMed1996

Induction of alpha/beta interferon and dependent nitric oxide synthesis during Chlamydia trachomatis infection of McCoy cells in the absence of exogenous cytokine.

The propensity of two Chlamydia trachomatis strains (L2/434/Bu [biovar LGV] and E/DK20/ON [biovar trachoma]) to induce putative host defense responses upon infection of McCoy (mouse) cell cultures was examined. Both strains induced production of alpha/beta interferon and nitric oxide (NO) by McCoy cells. NO synthesis was mediated by the inducible isoform of NO synthase as indicated by the ability of cycloheximide or the arginine analog NG-monomethyl-L-arginine to abolish NO production; the extent of the response was dependent upon the dose of chlamydiae applied. Incubation of McCoy cells with chloramphenicol prior to infection reduced NO production by strain 434 but not by DK20, suggesting that initial chlamydial metabolism was essential to induction by the LGV strain. Antibody inhibition studies indicated that NO synthesis was dependent upon production of alpha/beta interferon and induction via lipopolysaccharide. Overall, our findings show that chlamydiae are capable of the induction of interferon and NO in murine fibroblasts in the absence of exogenous cytokines. However, the role of NO as an antichlamydial effector could not be clearly demonstrated since treatment with an arginine analog, while suppressing NO production, gave no consistent enhancement of infected cell numbers.

Animals↗
PubMed1996

Lymphocyte infiltration in oesophageal carcinoma: lack of correlation with MHC antigens, ICAM-1, and tumour stage and grade.

Infiltration by T lymphocytes into oesophageal carcinomas was assessed immunohistochemically, total T lymphocyte numbers by staining for CD3 and activated T lymphocytes by staining for CD25. Five squamous carcinomas and seven adenocarcinomas, resected without neoadjuvant treatment, were studied. Computer aided quantitation showed that total numbers of tumour infiltrating CD3 positive cells were highly variable (range 48-1673 cells/mm2). They were located largely in the stromal (87.9-99.2%) rather than intratumoral regions. Up to 84% of tumour infiltrating T lymphocytes were CD25 positive, although the median figure was 33%. There was no correlation between T lymphocyte infiltration or activation and expression of class I and II histocompatibility antigens, intercellular adhesion molecule-1, tumour stage or grade. These results imply that the local inflammatory response in oesophageal carcinomas is deregulated, which may be a factor contributing to the aggressive nature of the tumours.

Adenocarcinoma↗
PubMed1996

Detection of human papillomavirus in vulval carcinoma using semi-nested PCR and restriction enzyme typing: a rapid and sensitive technique.

Aims-To develop a highly sensitive technique for the reliable detection and typing of human papillomavirus (HPV) DNA in clinical tissue.Methods-A two step, semi-nested PCR was used with primers spanning the L1 region of the HPV genome and capable of detecting HPV DNA of all known HPV types. The clinical samples were typed by digestion of the 412 base pair PCR product with Rsa I, generating unique fragments for each HPV type. Thirteen samples were screened by this method, including nine vulval carcinoma samples and four wart samples from the penis and vulva.Results-Experiments using DNA extracted from HPV DNA positive cell lines-that is, CaSki (HPV type 16) and HeLa (HPV type 18) established that the technique could detect as few as 50 HPV copies and that the predicted Rsa I fragments from HPV types 16 and 18 were generated. The predicted 412 base pair fragment was observed for all 13 clinical samples subjected to semi-nested PCR. Rsa I digestion of the product of the second round of PCR permitted the positive identification of the HPV type in most cases.Conclusions-This technique provides an effective and rapid means of detecting HPV DNA, in most cases providing the HPV type. High risk HPV types were always detected in the nine vulval carcinoma samples analysed. The amount of tissue available from the biopsy specimens was small, confirming the sensitivity of the method.

Journal Article↗
PubMed1995

Detection of circulating tumour cells with the magnetic activated cell sorter.

A technique has been developed for the detection of tumour cells in blood with the magnetic activated cell sorter (MACS). Colonic carcinoma cell lines and disaggregated primary tumours were used to establish optimal conditions of separation. A murine monoclonal antibody specific for epithelial cells was added to the suspension of leucocytes and tumour cells, followed by magnetic labelled goat antimouse antibody. The labelled tumour cells were retrieved by passing this suspension through a MACS separation column in a strong magnetic field. Tumour cells were detected at a dilution of 10 cells per ml blood. Tumour cells were identified in mesenteric blood in three of 24 patients undergoing surgery for colorectal cancer. This study supports the use of the MACS to detect circulating tumour cells.

Aged↗
PubMed1995

Lymphocytes infiltrating colorectal cancer have low proliferative capacity but can secrete normal levels of interferon gamma.

Significant numbers of infiltrating mononuclear cells are commonly observed in solid tumours, although their role in restricting tumour growth is not clear. Tumour-infiltrating lymphocytes (TIL) from 38 patients with colorectal cancer, in parallel with peripheral blood lymphocytes (PBL), were assayed to determine their ability to proliferate in response to concanavalin A (ConA), interleukin-2 (IL-2), ConA+IL-2, phorbol 12-myristate 13-acetate (PMA)+ionomycin ionomycin (IOM), and staphylococcal enterotoxin B(SEB). These reagents were selected to give a range of weak to strong proliferative responses either via or independent of the T cell receptor. Proliferation of TIL was significantly lower than that of PBL in all cultures: ConA (P < 0.001), IL-2 (P = 0.002), ConA+IL-2 (P < 0.001), PMA+IOM (P < 0.001), SEB (P = 0.002). In addition to the low proliferative capacity of TIL, production of cytokines by TIL may also play a role in control of tumour growth. We have assayed IFN gamma production in the supernatants from 16 paired TIL and PBL cultures, and tumour necrosis factor alpha (TNF alpha) in 6 paired cultures. TNF alpha concentrations were significantly lower in TIL cultures than in PBL cultures stimulated with ConA (P < 0.05), but no different in control or IL-2 stimulated cultures. IFN gamma levels did not significantly differ between PBL and TIL cultures, indicating that despite the restricted proliferative capacity of TIL, these cells remain capable of secreting significant amounts of IFN gamma.

Adenocarcinoma↗