Biomedical subjects

A G Morris

Publications and source records attributed to A G Morris.

At least 55 records · Page 3Linked to original sources

PubMed1995

CAG repeat expansions and schizophrenia: association with disease in females and with early age-at-onset.

An increase in the severity of schizophrenia through consecutive generations (anticipation) has been found in some studies of families with affected members. Anticipation in five neurological disorders is known to arise from the expansion of CAG repeats between generations of affected individuals. The 'repeat expansion detection' method was used to screen individual genomes for the size of such expansions in a sample of schizophrenic and normal subjects. Comparison of the frequency distribution of CAG expansions observed in schizophrenic patients to that for normal subjects, showed that there are significantly more expansions in patients (p = 0.048). When male and female subjects are considered separately, there is a highly significant difference in the distribution of repeat sizes found between affected and normal females (p = 0.0023) but no significant difference between affected and normal males. Overall there is a 28% excess of expansions observed in affected versus normal females, and their presence confers a relative risk of 4.12 (p < 0.005). In contrast, the frequency distribution of age-at-onset with respect to repeat size is nearly the same in male and female patients and, when the sexes are combined, the larger (CAG)69-136 expansions are associated with a younger age-at-onset (p = 0.02).

Adolescent↗

PubMed1995

Analysis of heat-shock protein expression in myeloid leukaemia cells by flow cytometry.

Expression of heat-shock proteins (hsp) was analysed in the leukaemic cells of 12 patients with acute myeloid leukaemia (AML) and nine patients with chronic myeloid leukaemia (CML). Using monoclonal antibodies to hsp70, hsp90 and hsp60 (ML30, a mycobacterial antigen with homology to human hsp60), we measured hsp levels by flow cytometry of permeabilized cells. Mononuclear cells from 10 healthy volunteers were also examined. The results demonstrate that hsp expression is significantly increased (P < 0.01) in the circulating cells of patients with AML compared with cells from CML patients, and compared with normal peripheral blood mononuclear cells. This increased pattern of expression was found for all three heat-shock protein families included in this study. Mononuclear cells from leukaemic patients showed a heterogenous pattern of hsp expression, between different patients, between cells from individual patients, and between the different hsp proteins examined. It is possible that hsp expression relates to the differentiation state or proliferative potential of these leukaemic cells.

Acute Disease↗

PubMed1995

Expression of HLA-ABC, HLA-DR and intercellular adhesion molecule-1 in oesophageal carcinoma.

AIM: To examine the expression of HLA-ABC and HLA-DR major histocompatibility (MHC) antigens and intercellular adhesion molecule (ICAM)-1 in normal, inflamed, metaplastic, and neoplastic oesophageal tissue and in freshly disaggregated tumours. METHODS: Sequential sections of frozen tissue and cytospins of freshly disaggregated tumour were stained using the ABC peroxidase system and monoclonal antibodies specific for HLA-ABC, HLA-DR and ICAM-1. RESULTS: Normal oesophageal tissue showed positive staining for HLA-ABC in the basal layers of the oesophageal squamous epithelium and on the epithelial cells of the submucosal oesophageal glands. HLA-DR and ICAM-1 were not detected in either of these cell types. In 20 of 37 (54%) carcinomas HLA-ABC was expressed weakly, with heterogeneous expression in nine (24%). Two tumours showed strong expression of HLA-ABC, but 15 of 37 (41%) were negative. HLA-DR and ICAM-1 were expressed weakly in six of 37 (16%) carcinomas without correlation with each other or with the expression of HLA-ABC. CONCLUSIONS: HLA-ABC is absent from a high proportion of oesophageal carcinomas (41%) and is otherwise variably and weakly expressed with strong expression in only a small fraction (3%). In other carcinomas there is a higher level of HLA-ABC expression. This discrepancy may partly explain the aggressive nature of oesophageal carcinomas. HLA-DR and ICAM-1 are not normally expressed on those cells from which oesophageal carcinomas are thought to arise. The limited expression found here could suggest a partial or inhibited immune response against oesophageal carcinoma. In vivo repressive factors may be involved.

Adenocarcinoma↗

PubMed1994

Clinical significance of in vitro donor-specific hyporesponsiveness in renal allograft recipients as demonstrated by the MLR.

A longitudinal study was carried out on 19 recipients of cadaveric renal allografts, monitoring their anti-donor and anti-third party responses in the mixed lymphocyte reaction (MLR) at the time of transplantation and at 3, 6, and 12 months post-transplant. Two patterns of responses were identified: in the first (n = 11), patients showed, or later developed, donor-specific hyporesponsiveness, and in the second (n = 8), patients had persistent antidonor and anti-third party responses. After 1 year, the serum creatinine, number of episodes of acute rejection and biopsy findings were compared in both groups. In the first group, the mean serum creatinine was 136.4 mmol/l, the total number of acute rejection episodes was three and in nine of the ten available biopsies, there were minimal cellular infiltrates and normal appearance of the glomeruli, tubules and blood vessels. In the second group, the mean serum creatinine was 163 mmol/l, the total number of acute rejection episodes was 12 and in five of the seven biopsies available, evidence of ongoing rejection was obtained. The difference in mean serum creatinine was not statistically significant (P > 0.05), but the difference in the numbers of acute rejection episodes was (P < 0.05). It is concluded that in some renal allograft recipients, a state of donor-specific hyporesponsiveness develops, and this state may be associated with better graft outcome at 1 year. These data may be useful in selecting patients for reduced immunosuppressive therapy.

Acute Disease↗

PubMed1993

Sequential changes in MHC antigen expression induced by the v-Ki-ras oncogene.

A series of early-passage cell lines were transformed with the v-Ki-ras oncogene with the aim of examining the effect of an activated ras gene on the ability of these cells to express major histocompatibility complex (MHC) antigens. These cell lines were found to undergo multiple phenotypic changes upon transformation and subsequent proliferation. At early passage, the predominant effect of ras was an increased ability to express class II antigens when induced with interferon gamma (IFN gamma). For class I antigens, maximum levels of expression induced with IFN gamma were largely unaffected, however, decreased sensitivity to induction with this lymphokine was noted. With subsequent in vitro or in vivo passage, both class I and class II antigen inducibility was attenuated. The latter phenotypic change was found to be transferable by coculture, implicating a soluble IFN gamma antagonist. Conditioned media from ras-transformed cells treated to activate their latent transforming growth factor beta (TGF beta) content mediated similar changes in MHC antigen inducibility, suggesting that TGF beta may be involved in modulating MHC antigen expression in ras-transformed cells.

Animals↗

PubMed1993

Stories from the sealed rooms: patient interviews during the Gulf war.

The mass deployment of gas masks to an entire population, which occurred in Israel prior to the Persian Gulf crisis and their use in early 1991, were phenomena without precedent. In addition to the historical significance, there were considerable health and psychological ramifications. This research examines the experiences of the Israeli public during the Gulf war using a qualitative methodological approach, narrative analysis. Interviews of a convenience sample of 60 patients attending primary care clinics were audio-recorded by three family physicians using an open-ended interview guide. Encounters took place at sites located in the north, south and centre of the country during the period of Iraqi missile attacks. Patients' stories were analysed using a multistep narrative analysis protocol. Seventy per cent of subjects reported deleterious health effects related to the missile attacks or civil defence measures, mainly psychological and neurological complaints, sleep disorders, gastrointestinal and respiratory symptoms. Recurrent themes and metaphors in the narratives most often focused on the difference of this war to others, the central involvement of the family, concern for children and identification and connection to the nation. The Scud missile attacks combined with the civil defence measures had significant impact on the population, as manifested in subjects' stories, symptoms, symbols and behaviour. Narrative analysis provided an efficient method to capture the rich texture of patients' experiences.

Adolescent↗

PubMed1992

Diet and dental caries among later stone age inhabitants of the Cape Province, South Africa.

Stable carbon isotope measurements and incidences of dental caries are presented for three groups of prehistoric human skeletons from different regions of the Cape Province, South Africa. The isotopic analyses of bone collagen demonstrate the importance of marine foods in the diet and vary through time, across space, and according to sex. The incidence of dental caries ranges from 0% among heavily marine-dependent individuals from the south-western Cape coast, to 17.7% among skeletons from an archaeological site on the south coast. The extremely high incidence of caries in a hunter-gatherer population may be related to lack of fluoride in the water.

Dental Caries↗

PubMed1992

The loss of class II MHC antigen expression by ras-transformed murine fibroblasts passaged as tumours correlates with increased tumorigenicity but is not mediated by T cells.

In several murine tumour systems, expression of class II major histocompatibility complex (MHC) antigens by tumour cells, either constitutive or inducible, correlates with reduced tumorigenicity as compared with equivalent class-II-negative cells, and CD4 phenotype T cells together with interferon gamma (which induces the expression of class II) may be involved in the control of the proliferation of class-II-expressing tumours. This implies a potential T-cell-mediated selection pressure against class II expression. To test this possibility, we have repeatedly passaged as tumours in euthymic, syngeneic mice ras-transformed murine fibroblast lines, which are class-II-inducible, to determine whether class-II-non-inducible variants are selected. We examined the expression of both class I and class II antigen in tumour cells re-established in vitro. It was found that the inducibility of class II, but not class I, expression rapidly diminished, correlating with augmented tumorigenicity. However, this loss of class II inducibility occurred in athymic as well as euthymic mice. Therefore, despite the fact that the tumorigenicity of these lines is augmented in euthymic mice depleted of CD4 T cells or interferon gamma, we found no evidence of T-cell-mediated selection against class II expression. The loss of class II expression observed must be due to mechanisms other than immune selection. The possibility that this might result from other soluble factors modulating the response to interferon gamma in vivo is discussed.

Animals↗

PubMed1992

Interferon-gamma receptor expression in chronic hepatitis B virus infection.

It is known that interferon-gamma (IFN gamma) is not effective in inducing a sustained inhibition of HBV replication in patients with chronic HBV infection in contrast to interferon-alpha (IFN alpha). To determine whether this was related to IFN gamma receptor (IFN gamma-R) underexpression, binding characteristics of IFN gamma to peripheral blood lymphocytes were studied in chronic HBV infection using radioiodinated recombinant IFN gamma. Peripheral blood lymphocytes from patients with chronic HBV infection (n = 20), normal healthy controls (n = 12) and patients with non-viral related chronic liver disease expressed a similar number of IFN gamma-R (medians (ranges): 1891 (1581-2515); 1916 (1589-2441); 1893 (1692-2104) sites/cell, respectively, p = N.S.) with a similar dissociation constant (Kd approximately 0.7-2.7 nM). There was no correlation between IFN gamma-R expression and serum transaminase, serum HBsAg and HBV-DNA titres and liver histology. IFN alpha therapy in vivo also did not enhance IFN gamma-R expression (n = 3). There is therefore, no evidence from this data that IFN gamma-R is underexpressed in patients with chronic HBV infection to account for the difference in clinical response to these two forms of therapy.

Adult↗

PubMed1991

Inducibility of class II major histocompatibility complex antigens by interferon gamma is associated with reduced tumorigenicity in C3H mouse fibroblasts transformed by v-Ki-ras.

Paired lines of C3H mouse fibroblasts transformed with murine sarcoma virus (Kirsten strain) were prepared that express high or low levels of class II major histocompatibility complex antigen after treatment with interferon gamma (IFN-gamma). Here, we described a comparison of the tumorigenicity of these lines in euthymic syngeneic and thymus-deficient nu/nu mice and in mice depleted of IFN-gamma. The class II-inducible cells are clearly less tumorigenic than the noninducible cells in syngeneic mice, but of similar tumorigenicity in nu/nu mice and in mice treated with antibodies to deplete IFN-gamma. We propose that in this system, IFN-gamma induction of class II antigens on the tumor cell surface operates to limit tumor growth; ras expression, which inhibits induction of class II antigens, prevents this and so allows tumor growth.

Animals↗

PubMed1991

Interferon-gamma inhibits serotonin release from mouse peritoneal mast cells.

Conditioned medium (CM) from concanavalin A-activated mouse spleen cells inhibits antigen-induced 5-hydroxytryptamine (5-HT) release from mouse peritoneal mast cells when added for 24 or 48 h to cell cultures containing monoclonal IgE sensitizing antibody. We present the following evidence that the spleen cell-derived inhibitory factor is interferon-gamma (IFN-gamma): (a) CM from Con A-activated spleen cells and from Chinese hamster ovary (CHO) cells transfected with the murine (Mu)IFN-gamma gene both produced a graded inhibition of 5-HT release when added to peritoneal cell cultures containing IgE and subsequently challenged with antigen; (b) the relative inhibitory potency of the two preparations corresponded to their relative IFN content as determined by antiviral bioassay; (c) the inhibitory activity of spleen cell CM and of CM from IFN-gamma gene-transfected CHO cells was abolished by treatment with a rat monoclonal MuIFN-gamma-neutralizing antibody, i.e. 5-HT release returned to control levels, and (d) a highly immunopurified preparation of recombinant MuIFN-gamma retained the inhibitory activity, and was active at concentrations as low as 2 U/ml. The inhibitory activity of IFN-gamma appeared to be a direct effect of the cytokine on mast cells, since CM generated for different time periods from unfractionated peritoneal cells treated with purified recombinant MuIFN-gamma contained no inhibitory activity other than IFN-gamma itself, as demonstrated by neutralization of the cytokine with monoclonal antibody. Furthermore, purified recombinant MuIFN-gamma was equally active on mast cells enriched by density centrifugation up to 95% purity as on unfractionated peritoneal cells (1%-2% mast cells). Purified recombinant MuIFN-gamma inhibited 5-HT release induced by a range of different cell activators, namely antigen, anti-IgE, compound 48/80 and calcium ionophore A23187. Hence inhibition is not specific to IgE-dependent activation of mast cells, but seems to be directed more generally at the secretory process of these cells.

Animals↗

PubMed1991

Changes in mandibular condyle morphology related to tooth wear in a prehistoric human population.

The exact relationship between tooth wear and changes in the shape of the articulating surface of the mandibular condyles is unknown. It is assumed that to some degree these changes are in response to the loads on the joint generated during chewing. Excavated skeletal remains from sites of primitive human habitation provide an opportunity to study the masticatory system of human beings in their natural context, with the features of form and function expressed to their full potential. Accurate measurements of the condylar head can also be made on such remains. A collection of skulls from an excavation site known as Oakhurst on the South African coast provided material for this study. Occlusal wear was measured using the scale devised by Molnar; approximal wear was assessed by measuring the size of the wear facet between the first and second molars. The width of the condyles were measured directly, and a method was devised to measure changes in the proportion of medial and lateral articulating facets. An increase in the size of the lateral facet of the condyle was found to be associated with increased tooth wear. It is suggested that the direction of condylar remodelling may give an indication of the reaction at the joint to optimal mastication.

Adult↗

PubMed1991

Identification of a spleen cell-derived factor that inhibits sensitization of murine peritoneal mast cells as interferon-gamma.

We present evidence that a spleen cell-derived factor that inhibits the sensitization of mouse peritoneal mast cells is IFN gamma. Conditioned medium (CM) from Con A-activated mouse spleen cells and recombinant MuIFN gamma both inhibited antigen-induced 5-HT release from peritoneal mast cells when added at the sensitization stage, but were without effect on presensitized cells. Both preparations were active at dilutions corresponding to similar levels of IFN activity (1-10 units/ml). The inhibitory activity of CM was blocked by a rat monoclonal MuIFN gamma-neutralizing antibody, thus confirming that IFN gamma was the active molecule.

Animals↗

PubMed1991

Interferon-alpha receptor expression and regulation in chronic hepatitis B virus infection.

Interferon-alpha elicits antiviral and immunoregulatory activities by binding to specific receptors on the cell surface. In this study, binding characteristics of interferon-alpha to peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection were studied using radioiodinated recombinant interferon-alpha 2b to determine interferon-alpha receptor numbers and dissociation constants. A single class of interferon-alpha receptor was demonstrated on peripheral blood mononuclear cells and mononuclear subsets. Peripheral blood mononuclear cells from patients with chronic hepatitis B virus infection (n = 20) and controls (n = 16) expressed a similar number of interferon-alpha receptors (484 +/- 175 vs. 511 +/- 168 sites/cell respectively, p = NS) with a similar dissociation constant (dissociation constant approximately 0.2 to 0.7 nmol/L). Expression of interferon-alpha receptors was similar in monocyte-enriched and lymphocyte-enriched fractions in both groups. Similar changes were observed in patients receiving alpha-interferon therapy. There was no correlation between interferon-alpha receptors expression and serum transaminase, serum HBsAg, serum HBV DNA, liver histological findings or the response to interferon-alpha therapy. After incubation of lymphocytes in vitro with interferon-alpha 2b (10 to 1,000 U/ml), interferon-alpha receptors number dropped by 42% to 80%, but this was associated with an increase in binding affinity (dissociation constant approximately 0.05 to 0.15 nmol/L) in both patients and controls. There was significant delay in the initial phase of receptor recovery in the patients with chronic hepatitis B virus infection compared with normal controls (days 1 and 2, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Reduced stimulation of helper T cells by Ki-ras transformed cells.

A number of viral genes and cellular oncogenes inhibit major histocompatibility complex (MHC) antigen expression at the cell surface. In the case of inhibition of class I MHC antigens by viral genes this results in a reduced recognition by antigen-specific cytotoxic T cells. The activated Ki-ras cellular oncogene carried by the Ki-murine sarcoma virus (Ki-MuSV) in contrast inhibits class II MHC (or Ia) antigen expression on transformed cells. We have studied how transformation with Ki-ras affects recognition by alloreactive helper T cells. We found that the Ki-ras inhibition of class II MHC antigen expression led to greatly reduced stimulation of alloreactive T cells to proliferate and to secrete interferon-gamma (IFN-gamma). These findings support our hypothesis that the ability of an oncogene to reduce class II MHC antigen expression is crucial to its ability to produce tumour cells.

Animals↗

PubMed1991

Hepatic interferon-alpha gene transcripts and products in liver specimens from acute and chronic hepatitis B virus infection.

In this study we have examined the localization of interferon-alpha in liver tissue from acute and chronic hepatitis B virus carriers to establish whether the defect in interferon-alpha production reported in chronic hepatitis B virus infection is at a pretranscriptional or posttranscriptional level using in situ hybridization and immunohistochemical techniques. Interferon-alpha messenger RNA transcripts and the immunoreactive protein were abundant in liver tissue and in particular in hepatocytes from patients with acute hepatitis B virus infection who subsequently recovered. In contrast interferon-alpha polypeptide was present in a significantly lower number of sinusoidal cells, mononuclear cells and hepatocytes in chronic hepatitis B virus carriers. Although a high proportion of patients with chronic hepatitis B virus infection had cells that expressed interferon-alpha messenger RNA transcripts, the number of such cells was significantly less than in acute hepatitis B virus infection, indicating that the defect in the hepatic interferon-alpha synthesis is at the level of gene activation. Furthermore, using double immunohistochemical staining, the number of hepatocytes containing HBcAg correlated inversely with the proportion of neighboring sinusoidal cells expressing interferon-alpha. These data support previous observations that interferon-alpha production is reduced in chronic hepatitis B virus infection and are consistent with the view that this cytokine is important in the clearance of the virus.

Acute Disease↗

PubMed1990

Major histocompatibility complex antigens in v-Ki-ras transformed cells: the different antigens are expressed and induced by interferons independently of one another and of the anti-viral state.

A series of cell lines, which differed in their expression of class I (H-2K) or II (I-A) major histocompatibility complex (MHC) antigens, was derived from a line of C3H/He (H-2k) mouse embryo fibroblasts transformed by the v-Ki-ras oncogene. These were prepared by fluorescence-activated cell sorting of cells stained for these antigens either without interferon (IFN) treatment or after induction of antigen expression by either IFN-alpha beta or IFN-gamma, selecting for low or high staining. Cells selected for low (undetectable) constitutive H-2Kk expression were still strongly inducible by either IFN; cells selected for high constitutive expression were induced by IFN to express still higher levels. In all cell lines induction of H-2Kk with one IFN type was paralleled by induction with the other. Expression of H-2Kk appeared largely independent of H-2Dk; in lines which were selected for low H-2Kk expression (constitutive or induced), H-2Dk expression was not much reduced, and lines selected for high H-2Kk expression showed only modest augmentation of H-2Dk. Varying inducibility of I-Ak by IFN-gamma was not closely paralleled by H-2K inducibility by either IFN-alpha beta or -gamma, with again only weak correlation of high and low expression of H2-Kk and I-Ak. On the other hand, expression of I-Ak seemed to be correlated with I-Ek. None of these variable effects could be attributed to differing sensitivity to IFN-alpha beta or -gamma since all the lines showed about the same sensitivity to the anti-viral effects of IFN.

Animals↗

PubMed1989

A probable case of prehistoric kidney stone disease from the northern Cape Province, South Africa.

During the excavation of isolated graves along the north shore of the Orange River in the Cape Province of South Africa, a skeleton was uncovered that showed two large calcareous deposits near the lumbar region of the vertebral column. The individual was an adult female of about 55 years of age at the time of death. The calcified residue did not in any way resemble the external or internal anatomical form of a kidney, but X-ray powder diffraction analysis and scanning electron microscopy identified the material as apatite (Ca10(PO4)6 (OH)2), a common constituent of human urinary calculi. It is postulated that the bilateral calcification was the result of a chronic renal disorder. Although it is rarely possible to identify the cause of death from skeletal remains alone, the disorder as seen in this specimen would appear to have been very severe and may well have been the ultimate cause of death.

Apatites↗