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Biomedical subjects

L Sviland

Publications and source records attributed to L Sviland.

At least 55 records · Page 3Linked to original sources
PubMed1994

Monoclonal anti-TNF-alpha suppresses graft vs host disease reactions in an in vitro human skin model.

Graft vs host disease (GVHD) following allogeneic marrow transplant in humans is known to be mediated in part by cytokines. Tumour necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) are considered to be critical in the mechanism. A commercially produced antibody to TNF-alpha (CB0006) was tested in vitro to assess its ability to suppress mixed lymphocyte reactions (MLR). Peripheral blood mononuclear cells treated and untreated with CB0006 were also tested for their ability to elicit a graft vs host reaction (GVHR) in vitro in a human skin-explant model for GVHD. The results showed that CB0006 could inhibit mixed lymphocyte culture (MLC) proliferative responses and that in vitro antibody treated responder cells were less effective in causing GVHR in vitro skin-explant assays. CB0006 was also shown to inhibit MLC supernatant induced GVHR.

Antibodies, Monoclonal↗
PubMed1994

Diagnostic features of transfusion associated graft versus host disease.

AIMS: To define the immunopathological profile of transfusion associated graft versus host disease (TA-GvHD) to elucidate its pathophysiology and to determine if any features are of diagnostic value. METHODS: Nine patients (age range 14-61 years) who developed histologically confirmed TA-GvHD between 1989 and 1992 were studied. Immunohistochemical analysis of frozen and formalin fixed skin biopsy tissue was performed. Sections were stained with antibodies to CD3, CD8, CD4 and HLA-DR, using a routine streptavidin-biotin technique with standard diaminobenzidine development. RESULTS: All biopsy specimens showed aberrant positive expression of HLA-DR by epidermal keratinocytes. In four patients, all of whom died, HLA-DR was diffusely expressed throughout the epidermis; in the other five cases keratinocyte expression of HLA-DR was more focal. In all biopsy specimens T cells had infiltrated the dermis and epidermis. In all nine cases CD4+ T helper/inducer cells were the predominant T cells. DISCUSSION: Immunohistochemical studies are of value in the diagnosis of TA-GvHD. Aberrant keratinocyte expression of HLA-DR and dermal and epidermal infiltration of CD4+ T cells are immunopathological features of TA-GvHD. Immunohistochemical analysis of skin biopsy tissue using antibodies to these markers is thus a useful investigation in pancytopenic patients presenting with unexplained rashes.

Adolescent↗
PubMed1994

Late development of graft-versus-host disease in an autologous BMT recipient.

Clinical and histological changes consistent with GVHD have been described in recipients of both syngeneic and autologous grafts. The mechanism of autologous GVHD is well documented. However, cases of autologous GVHD previously reported have all occurred within the first 2 months post-BMT. We report the case of an autologous BMT recipient in whom histological features consistent with GVHD emerged 7 months post-BMT, which may have implications for the long-term follow-up of autologous marrow graft recipients.

Bone Marrow Transplantation↗
PubMed1994

Cytokine involvement in predicting clinical graft-versus-host disease in allogeneic bone marrow transplant recipients.

An in vitro skin explant model has been used to predict the severity of acute graft-versus-host disease (GVHD) in 34 HLA-identical bone marrow transplant recipients (correlation coefficient 0.6 p < 0.001). Supernatants from HLA-matched patient/donor mixed lymphocyte cultures (MLCs) were analysed for levels of tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma). High levels of both cytokines correlated with the development of GVHD grades II or above (p < 0.05). The supernatants were also tested for induction of class II MHC antigen expression on third party skin and results correlated with clinical outcome in 17 of 22 cases (77%) (correlation coefficient 0.65, p < 0.001). The results suggest that measurement of both TNF alpha and IFN gamma in HLA-matched MLC supernatants is of predictive value and that the skin explant model is a useful model for studying the aetiology of GVHD in humans.

Adolescent↗
PubMed1993

Pathogenesis of GVHD: role of herpes viruses.

The pathogenesis of GVHD is not fully elucidated. Some groups of patients have a higher risk of developing GVHD post-BMT than others. Environmental factors may be important. Much attention has focused on the role of viruses, particularly herpes viruses, in GVHD. CMV in particular has been implicated as a pathogenic agent. Data from animal work and from observations of the frequent clinical association of CMV with GVHD have suggested a pathogenic link. Several large multi-centre seroepidemiological studies have been performed in an attempt to clarify this issue. This review discusses the data implicating herpes viruses in the pathogenesis of GVHD and considers the mechanisms by which viruses may exacerbate or initiate GVHD. Implications for the management of allogeneic BMT patients are discussed.

Animals↗
PubMed1993

Prognostic importance of histological and immunopathological assessment of skin and rectal biopsies in patients with GVHD.

Skin and rectal biopsies from patients with GVHD were examined histologically and immunopathologically before and after treatment for the disease. The patients were divided into two groups: those showing a good response to treatment and those showing a poor or no response. The aims of the study were to assess the possibility of predicting the response to treatment and to compare good and poor responders after treatment. The results show that there are no features on either skin or rectal biopsy that could identify those patients with early GVHD who would respond to treatment. Following treatment with steroids there was no change histologically in the grading of the skin biopsy whereas the rectal biopsy showed improvement in six of nine good responders and no improvement in the poor responders. There was an increase in infiltrating lymphocytes in both the skin and rectum of patients showing a poor response and this is most likely due to the ongoing immune reaction. The pre-treatment biopsy did not show any features that would predict this development and was therefore of no prognostic value. However, examination of skin and rectal biopsies may aid in determining whether patients are responding to the treatment given for GVHD.

Adolescent↗
PubMed1992

Increase in severity of graft versus host disease by cytomegalovirus.

An allogeneic transplant recipient developed severe graft versus host disease (GvHD) 48 days after transplantation that was concomitant with a cytomegalovirus (CMV) viraemia, from which she subsequently died. CMV infection was detected in blood by the polymerase chain reaction and later in tissue by immunohistochemical techniques. CMV should be considered in patients in whom GvHD does not respond to appropriate treatment, and this case suggests that herpes viruses may increase the severity of GvHD by synergistically enhancing the graft versus host reaction.

Adult↗
PubMed1992

Human herpes virus 6 and endogenous biotin in salivary glands.

AIMS: To detect the presence of human herpes virus 6 (HHV6) and endogenous biotin in paraffin wax embedded and frozen salivary glands. METHODS: Two stage indirect and streptavidin-biotin immunoperoxidase techniques were used to visualise the antigens. RESULTS: HHV6 could not be shown in any of the tissues. However, considerable endogenous biotin antigenicity was detected in the glandular elements of the paraffin wax embedded material. CONCLUSIONS: Results obtained with avidin-biotin detection systems should be interpreted with caution, especially when glandular epithelium is being stained. This may apply to both immunoperoxidase and in situ hybridisation techniques. The use of an anti-biotin antibody as a standard control should be considered.

Biotin↗
PubMed1991

Immunopathology of early graft-versus-host disease--a prospective study of skin, rectum, and peripheral blood in allogeneic and autologous bone marrow transplant recipients.

The immunopathological appearances of skin and rectum in 64 autologous and allogeneic recipients were determined before and after bone marrow transplantation. Patients who developed acute graft-versus-host disease were biopsied as soon as a clinical diagnosis was made. At the same time peripheral blood samples were collected for comparative analysis. Immunohistological and morphometric techniques were employed using a panel of monoclonal antibodies to T lymphocytes and subsets, B lymphocytes, natural killer cells, macrophages, and Langerhans cells. A reduction in the CD4/CD8 ratio after BMT was seen in skin and rectal biopsies from both autologous and allogeneic recipients with or without GVHD. The same pattern was observed in blood samples taken at the same time. Langerhans cells were reduced in the skin in all patients after BMT, probably by the conditioning regimen. Only a few cells expressing activation or natural killer cell markers were present and there were no changes observed in the macrophage population. This study has provided no evidence to implicate either CD4- or CD8-positive T lymphocytes as the initiators of the cellular damage in acute GVHD. The distribution of lymphocyte subsets in the blood was similar to that in the tissues, suggesting that the tissue changes reflect the pattern of lymphocyte repopulation after BMT and may have little bearing on the pathogenesis of GVHD.

Adolescent↗
PubMed1991

Demonstration of direct involvement of cytokines in graft-versus-host reactions using an in vitro human skin explant model.

A human skin explant model was used to investigate the role of cytokines in graft-versus-host reactions (GVHR). Responder cells from HLA mismatched mixed lymphocyte cultures (MLC) produced GVHR (Grades I-III) in skin explant assays. Cell-free supernatants from these experiments also induced similar histopathological changes in the skin. The greatest degree of correlation between the GVHR observed with responder cells and the supernatant was shown with CD4 enriched MLC (p less than 0.001). Supernatants were assayed for tumour necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN gamma) and CD4 enriched MLC populations produced high levels of these cytokines. These results correlated with the grade of GVHR observed in skin explant assays. The GVHR produced by the supernatant alone could be inhibited by both anti-IFN gamma and anti-TNF alpha polyclonal antibodies. The results suggest that TNF alpha and IFN gamma are directly involved in tissue damage during graft-versus-host disease in allogeneic transplant in man.

Cytokines↗
PubMed1991

Endothelial changes in cutaneous graft-versus-host disease: a comparison between HLA matched and mismatched recipients of bone marrow transplantation.

Histological features of endothelial and vascular changes seen in cell mediated immune reactions were evaluated in skin biopsies from 44 HLA matched and mismatched recipients of bone marrow transplantation. The mismatched group (n = 24) was further subdivided into 'D-mismatched' (n = 14) and 'AB-mismatched' (n = 10). All patients had clinical grade III and histological grade II graft-versus-host disease (GVHD). Comparison groups consisted of skin biopsies from 10 non-GVHD cases. Histological evidence of endothelial damage including perivascular factor VIII related antigen deposition was assessed and compared between the groups. The results showed that all patients post-transplant had evidence of a non-specific vascular response consisting mainly of a perivascular lymphocytic infiltrate, perivascular oedema and factor VIII related antigen extravasation. However, a significant difference between matched and mismatched patients who developed GVHD was the more frequent observation of perivascular nuclear dust in the HLA mismatched group (p less than 0.01) suggesting a greater degree of endothelial cell damage in these patients.

Bone Marrow Transplantation↗
PubMed1990

Virus infections in bone marrow transplant recipients: a three year prospective study.

Over three years 81 consecutive bone marrow transplant recipients (32 allogeneic and 49 autologous) who received prophylaxis with acyclovir, were studied for symptomatic virus infection. Thirty nine infections were documented in a total of 28 patients. Thirty two infections were mild, five were moderately severe, and two were severe. Cytomegalovirus infection occurred in only six allogeneic recipients. Herpes simplex virus and varicella zoster virus infections occurred infrequently. Seven patients who were considered at the time of death to have died due to an infectious cause were studied virologically at necropsy. In only one patient was a virus infection thought to have been the cause of death. Prophylaxis with acyclovir may have influenced the rate and clinical prominence of herpes virus infections. In this study viruses were considered to have had a relatively minor role in causing morbidity and mortality.

Acyclovir↗