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Biomedical subjects

A J Malcolm

Publications and source records attributed to A J Malcolm.

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

Expression of mu class glutathione S-transferase correlates with event-free survival in childhood acute lymphoblastic leukemia.

Expression of the main classes (pi, mu, and alpha) of glutathione S-transferase (GST) was assessed in the blasts of children presenting with acute lymphoblastic leukemia using an immunohistochemical technique. Bone marrow trephine biopsies obtained at presentation from 71 cases were studied (42 boys, 29 girls; age range, 6 months-14 years; median age, 4 years) and expression was correlated with event-free survival. The period of follow-up was 12-108 months, during which time 21 patients (30%) relapsed. All the samples examined were negative for alpha class GST. Samples from 8 patients, all of whom remained in remission at the time of analysis, were found to be negative for pi class GST at presentation. Samples from 44 (patients were negative for mu class GST (62%); of these, 36 patients (82%) remained in remission. In comparison, of the 27 patients who were positive for mu class GST, only 14 (52%) remained in remission. Analysis of event-free survival demonstrated that expression of mu class GST predicts a 3-fold increased risk of relapse (95% confidence interval, 1.25-7.26). This risk factor appears to be independent of other recognized prognostic factors.

Adolescent↗
PubMed1994

MHC class II and ICAM-1 expression and lymphocyte subsets in transbronchial biopsies from lung transplant recipients.

The expression of MHC class II antigens and ICAM-1 and the composition of lymphocyte infiltrates have been studied in frozen sections of transbronchial biopsies from lung transplant recipients. First, biopsies obtained from patients who showed acute rejection, OB, and normal features were compared. Second, we compared first-year biopsies from patients developing OB and patients with a good clinical outcome. HLA-DR was widely expressed on epithelia and vascular endothelium. Increased vascular HLA-DP expression was found in OB biopsies. In OB patients there was a significantly increased frequency of bronchial HLA-DP and vascular HLA-DQ expression. Expression of ICAM-1 by bronchial and bronchiolar basal cells, a phenomenon not reported previously in humans, was seen in a small number of biopsies. CD8 predominant lymphocytic infiltrates were present in all groups and were increased in OB biopsies and OB patients. Increased numbers of CD4-positive cells were found in rejection and OB when compared with normal biopsies. These findings support an immunological basis for the development of OB.

Antigens, CD↗
PubMed1994

Organizing pneumonia following pulmonary transplantation and the development of obliterative bronchiolitis.

Twelve patients receiving lung transplants between 1988 and 1992 who developed clinical and histological features of obliterative bronchiolitis (OB) were compared with a group of 13 patients with good stable lung function (FEV1 more than 80% of predicted). Histological features of 180 biopsies were studied from the first postoperative year in order to assess whether any were associated with the development of OB. Clinically and histologically defined pulmonary rejection occurring after the first month was more frequent in OB patients (P = 0.03). Organizing pneumonia that was associated with acute rejection but not with nonviral infection was also seen more frequently in OB patients (P = 0.003). When all available lung transplant recipients surviving beyond 18 months were included in analyses, organizing pneumonia in the first year was associated with an increased relative risk of developing OB of 2.26 (95% CL 1.19-4.29), and the occurrence of coexistent organizing pneumonia and pulmonary rejection gave a relative risk for OB of 6.33 (95% CL 1.61-24.94). An increased incidence of histologically defined organizing pneumonia in OB patients has not been described previously. Furthermore the coexistence of organizing pneumonia with pulmonary rejection in the first year posttransplantation is a strong predictive factor for the development of OB.

Adult↗
PubMed1994

Cytogenetic abnormalities of small round cell tumours.

Between 1987 and 1991, cytogenetic studies were carried out on small round cell tumours of 68 patients from the Northern Health Region of England. Clonal chromosome abnormalities were found in 30, comprising 15 neuroblastomas, 7 Ewing's tumours, 7 rhabdomyosarcomas, and 1 granular cell tumour. Characteristic rearrangements were found in five cases of Ewing's tumour [all with translocation t(11;22) (q24;q12)] and in four cases of rhabdomyosarcoma [all with evidence of translocation t(2;13) (q35-37;q14)]. In one case of Ewing's tumour and three of rhabdomyosarcoma, the cytogenetic findings were important in diagnosis. Within the neuroblastomas, examples were found of hyperdiploidy, 1p rearrangements, double minute chromosomes, and homogeneously staining regions, but too few cases were available for prognostic associations to be assessed. Our findings confirm the diagnostic importance of chromosome abnormalities in small round cell tumours and indicate that cytogenetic analysis should be an intrinsic part of the initial investigations of all patients with such tumours.

Adolescent↗
PubMed1994

Characterization of a subtype of primary osteoclastoma: extracellular calcium but not calcitonin inhibits aggressive HLA-DR-positive osteoclastoma possessing 'functional' calcitonin receptors.

We report here a case of primary osteoclastoma that despite possessing HLA-DR-positive status and 'functional' calcitonin receptors, exhibited aggressive in vitro and in vivo bone resorptive activity. In the osteoclast bone slice assay employing scanning electron microscopy, the giant cell-mediated bone resorption was uninhibited by salmon calcitonin (10 nM) and significantly inhibited by raised extracellular calcium (20 mM). In Fura-2AM based microspectrofluorimetric assays, the presence of the 'functional' calcitonin receptors was ascertained by a rise in intracellular calcium induced by calcitonin and high extracellular calcium. These findings provide evidence for a hitherto unrecognized subtype of giant cells that have HLA-DR-positive status, exhibit avid bone resorptive activity, but remain insensitive to calcitonin despite possessing calcitonin receptors.

Adult↗
PubMed1994

Rapid detection of prognostic genetic factors in neuroblastoma using fluorescence in situ hybridisation on tumour imprints and bone marrow smears. United Kingdom Children's Cancer Study Group.

A number of biological factors have been identified which correlate with prognosis in neuroblastoma. Among these are genetic aberrations, including ploidy, deletions of chromosome 1p and N-myc amplification. Conventional methods of detecting these changes, such as tissue culture for karyotyping and Southern blotting, are time-consuming and yield interpretable results in only a small proportion of cases. We have developed interphase fluorescence in situ hybridisation for use on tumour imprints and bone marrow smears, allowing rapid visualisation of the relevant genetic changes. Valuable prognostic information is therefore available in a few days: the results in our cases were later confirmed by conventional methods. In the foreseeable future it will be possible to define distinct prognostic categories on the basis both of this genetic information and other parameters, and separate therapeutic strategies may then be employed for the different patient groups.

Bone Marrow↗
PubMed1994

Glutathione S-transferase in bone marrow metastases of disseminated neuroblastoma.

Antisera to each of the three main cytosolic forms of glutathione S-transferase (GST; alpha, mu, and pi) has been used to characterise GST expression by metastatic neuroblastoma in bone marrow trephine biopsies taken from 15 patients at presentation and from five of this group at relapse. There was no correlation between expression of extra-nuclear alpha or mu GST and outcome, and no consistent pattern at relapse. Seven of eight expressing nuclear pi GST at presentation died of resistant disease. Three of five cases with no detectable nuclear pi class GST remain alive and disease free. The results provide no encouragement for further investigation of alpha or mu GST in this disease but larger studies of uniformly treated patients may show whether nuclear pi GST expression at presentation indicates likely relapse.

Adolescent↗
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↗
PubMed1993

Chemotherapy in the management of infantile fibrosarcoma.

Infantile fibrosarcoma (IF) has traditionally been treated with surgery, which may have considerable morbidity. Chemotherapy has been suggested in order to reduce the need for extensive surgery. Nine children with histologically confirmed IF who received chemotherapy are described. Six children were treated with chemotherapy initially, two following conservative surgery, and one following recurrence after surgery. All received vincristine (V) and actinomycin D (A), and six received additional drugs including ifosfamide (I), cyclophosphamide (C), adriamycin (Ad), etoposide (E), and cisplatinum (CDDP). Objective responses were achieved in eight: three responded completely (CR), two responded partially (PR), which allowed conservative surgery, one had stable disease, one had an initial PR, but subsequently had tumour recurrence 1 month after cessation of treatment, necessitating further surgery and chemotherapy, and one had an initial PR but died following local and regional metastases. One child had no response to chemotherapy but is alive with stable residual disease. Thus, five of nine children achieved a CR--three with chemotherapy alone. With the inclusion of chemotherapy as part of their treatment, five children, for whom curative surgery may have resulted in amputation, remain alive with limbs intact. Chemotherapy including V and A should be given to infants with fibrosarcoma in whom curative surgery would be mutilating.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Identification of alpha-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man.

Human anti-pig antibodies were obtained by perfusing pig hearts (n = 4) and kidneys (n = 8) with human AB or O plasma followed by elution with 3 M NaSCN. The antibodies were screened against a panel of 132 synthetic carbohydrates conjugated to bovine serum albumin using an enzyme-linked immunoassay. An anti-immunoglobulin antibody was also used to detect immunoglobulin deposits on pig tissues. Four carbohydrate molecules with a terminal alpha-galactose residue bound all but one of the human anti-pig kidney antibodies and most of the anti-pig heart antibodies. These were: (i) alpha Gal(1-->3)beta Gal(1-->4)beta GlcNac (linear B type 2); (ii) alpha Gal(1-->3)beta Gal(1-->4)beta Glc (linear B type 6); (iii) alpha Gal(1-->3)beta Gal(B disaccharide); and (iv) alpha Gal(alpha-D-galactose). Immunoglobulin deposition was documented post-plasma perfusion in all pig hearts and particularly strongly in all pig kidneys. These results suggest that human anti-pig antibodies are mainly directed against alpha-galactosyl structures. Extracorporeal immunoadsorption of human plasma through columns of the specific synthetic carbohydrate(s) might lead to depletion of anti-pig antibodies and allow discordant xenografting in man. Alternatively, the infusion of the specific carbohydrate(s) for a period of several days might result in neutralization of the anti-pig antibodies and allow accommodation to take place.

ABO Blood-Group System↗
PubMed1993

p53 expression in three separate tumours from a patient with Li-Fraumeni's syndrome.

The Li-Fraumeni cancer syndrome is a rare autosomal dominant syndrome, characterised by the occurrence of diverse mesenchymal and epithelial neoplasms at multiple sites. It has recently been shown that some of these individuals have a germ line mutation of the p53 tumour suppressor gene. The case of one member of such a family who has now developed three separate primary malignant tumours is reported. All three tumours expressed mutant p53 protein.

Adult↗
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↗