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Biomedical subjects

A Ting

Publications and source records attributed to A Ting.

At least 91 records · Page 5Linked to original sources
PubMed1985

Evidence that lysolecithin is an important causal agent of atherosclerosis.

We examine the hypothesis of Portman et al. (1970) that lysolecithin is a causal agent of atherosclerosis. Four lines of argument support this hypothesis. (1) Lysolecithin is present, taken up and can act. Large amounts of lysolecithin are formed in plasma concomitant with triglyceride transport and it is readily taken up by arteries and retained for some time. Lysolecithin in aortic intima increases several-fold early in the induction of atherosclerosis in animals. From model system studies it is plausible that physiological doses of lysolecithin have physiologically significant effects. (2) At least one plausible mechanism of action can be formulated: stimulation of smooth muscle cell division due to lysolecithin-increased Ca2+ uptake. (3) The hypothesis is consistent with, and rationalizes, many literature observations in that inferred lysolecithin levels or production rates are appropriately correlated with a variety of positive and negative risk factors to a degree highly unlikely by chance. We found no data contradicting the hypothesis and only one piece weakening it. (4) A mechanism is outlined showing that low density lipoprotein receptor deficiency, the severest known risk factor, should cause the delivery of very high lysolecithin doses to artery walls. We conclude that the evidence, although indirect, is strong enough to give direct tests a high priority.

Animals↗
PubMed1985

Renal transplantation in the United Kingdom and Ireland--the centre effect.

A detailed audit was done of eight of the twenty-nine transplant centres serving the UK and Ireland. These 8 centres account for one-third of the total renal transplant operations in these two countries. Information was obtained from each centre by means of a comprehensive questionnaire, a 1 1/2 day visit by the three authors, and an analysis of 50 consecutive first cadaver transplants. The 8 centres were chosen in the knowledge that 4 had high and 4 had low 3-month graft-survival rates. Our audit confirmed a centre effect, with a range in 1-year patient survival of from 82% to 96% and of first cadaver graft survival of from 54% to 82%. The two main factors affecting success rate were the rate of irreversible acute rejection and death with a functioning kidney. Our investigations suggested that the centre variation in acute rejection was influenced by blood transfusion and the variation in mortality by steroid dose and recipient age. Careful and well-organised clinical management cannot be easily quantified but was thought to have an important influence. Widespread adoption of pre-transplant blood transfusion and increasing use of cyclosporin will probably contribute to the further lessening of the centre effect which has already been observed over the past few years.

Aged↗
PubMed1985

Alloimmunisation to HLA antigens following transfusion with leucocyte-poor and purified platelet suspensions.

24 previously non-transfused patients were given three transfusions of 200 X 10(8) platelets at 14-day intervals. Group I (12 patients) received leucocyte-poor platelet suspensions with a mean contamination of 15 X 10(6) leucocytes per transfusion. Group II (12 patients) received platelets with less than 5 X 10(6) leucocytes per transfusion. 5 patients in group I and no patients in group II developed lymphocytotoxic antibodies (p = 0.037). Platelets with fewer than 5 X 10(6) leucocytes did not seem to stimulate a response to major histocompatibility antigens, but with a small contaminating dose of leucocytes appeared to be highly immunogenic.

Adolescent↗
PubMed1985

Ulcerative colitis and HLA phenotype.

The distribution of HLA A, B, C, DR antigens was investigated in a British population with ulcerative colitis. Fifty six patients were typed for HLA, A, B, C and 46 additionally for DR. No association was found between the HLA phenotype and the presence or absence of ulcerative colitis. Serum from 52 patients was tested for the presence of the anticolon antibody. There was no relation between the presence of the antibody and the HLA phenotype. Finally, no correlation was found between the HLA phenotypes, the age of onset of the disease, the extent and the clinical course.

Adolescent↗
PubMed1984

The detailed distribution of HLA-A, B, C antigens in normal human organs.

We have used a monoclonal antibody, PA2.6, directed against the heavy chain of HLA-ABC antigens to study the detailed tissue distribution of MHC class I antigens. Normal tissues from throughout the human body were obtained fresh from organ donors or operative specimens and were snap-frozen in liquid nitrogen within 1-2 hr of removal. Frozen sections were then studied using a sensitive peroxidase-antiperoxidase immunohistological technique. The results of our study show that class I antigens could be detected on most, but not all, the nucleated cells in the body. They were only weakly detectable in several tissues including endocrine cells in the thyroid, parathyroid, pituitary and islets of Langerhans in the pancreas and on gastric mucosa, the myocardium, skeletal muscle, and hepatocytes in some of the specimens. Spermatozoa were positively stained in the testis, but as they moved up into the epididymis class I antigens were no longer detectable. We found that class I antigens were not detectable on corneal endothelium, some Brunner's glands in the duodenum, villous trophoblast, central nervous system neurones, the exocrine portion of the pancreas, and acinar cells in the parotid. We conclude, therefore, that class I antigens are not ubiquitous, as previously thought.

Adult↗
PubMed1984

The detailed distribution of MHC Class II antigens in normal human organs.

In a previous article we described the detailed tissue distribution of MHC class I antigens. In this study, we have used a monoclonal antibody, NFK1, to study the tissue distribution of MHC class II antigens. This antibody, which detects a monomorphic determinant common to the DR, SB, and DC molecules, was used to stain frozen sections of normal tissues from throughout the human body by a sensitive peroxidase-antiperoxidase immunohistological technique. Although previous studies, both in animal models and in human beings, have shown that class II antigens are expressed on a limited number of nonlymphoid tissues, our study has extended the spectrum of tissues on which this class of antigens is detectable. Epithelial cells in a number of organs were positively stained--these include the tongue, tonsils, epiglottis, trachea, small intestine, urethra, epididymis, and proximal renal tubules. Lymphatics throughout the body appeared to express class II antigens. Capillaries in brain, testis, and placenta appeared not to express class II antigens, but in the rest of the body they showed strong and uniform staining. These and other observations, and their implications, are discussed in relation to previously published studies.

Antibodies, Monoclonal↗
PubMed1984

The influence of HLA-A,B and -DR matching and pregraft blood transfusions on graft and patient survival after renal transplantation in a single centre.

The influence of HLA-A,B and DR matching and pregraft blood transfusions on the graft and patient survival rate of 305 recipients of first cadaver grafts in a single centre has been studied. All three factors significantly influenced the graft survival rate. The effect of HLA-A,B matching became apparent only after a follow-up period of 3 years whereas the effect of HLA-DR matching was seen within 3 months after transplantation. The survival rate of HLA-DR compatible grafts was not improved by additional HLA-A,B matching, but that of HLA-DR mismatched grafts was improved by HLA-A,B matching. The HLA-DR matching effect was seen in both transfused and in nontransfused patients. However, the highest graft survival rate seen was in the pregraft transfused patients who received a DR compatible kidney (87% at 1 year and 80% at 5 years). Both HLA-A,B and DR matching significantly increased the patient survival rate whereas blood transfusion did not. The lower survival rate of patients receiving HLA poorly-matched grafts was not related to the amount of methylprednisolone received during the first 3 months after transplantation, the age of the patient, or whether the patient was considered medically high risk at the time of transplantation.

Adult↗
PubMed1984

The problem of cytomegalovirus infection in renal allograft recipients.

A prospective study of the effects of cytomegalovirus (CMV) infection on 145 recipients of 155 renal allografts is reported. Immunosuppression was either with azathioprine and low-dose prednisolone (103 transplants) or with Cyclosporin A (52 transplants). Sixty-one cases of CMV infection were diagnosed; of those 21 were primary (i.e. in CMV sero-negative recipients) and 40 were secondary (i.e. in previously sero-positive recipients). The infection rate in patients treated with azathioprine and low-dose prednisolone did not differ from the rate in those treated with Cyclosporin A. Eighteen of the 21 primary CMV infections were clinically overt; several of these patients became seriously ill, and one of them died. Only four of the 40 secondary infections were overt, and these were all mild. Graft and patient survival were not adversely affected by CMV infection. Indeed the group with secondary CMV had significantly better survival rates than the uninfected sero-positive or sero-negative patient groups. Recommendations to minimise the effects of primary CMV infections are given.

Actuarial Analysis↗
PubMed1984

Class 1 major histocompatibility complex antigens on human extra-villous trophoblast.

Using immunohistological techniques, class 1 products of the major histocompatibility complex (MHC) have been demonstrated on various forms of human extra-villous trophoblast in placental tissues taken from first, second and third trimester pregnancies. This contrasts with the absence of class 1 MHC antigens on all forms of villous trophoblast. The extra-villous trophoblast which reacted with antibodies to monomorphic class 1 MHC antigens consistently failed to bind HLA-A or HLA-B antibodies specific for the foetal phenotype. This suggests, but does not prove, that the MHC antigen expression of trophoblast may be restricted to HLA-C or some other undefined class 1 antigen.

Antibody Specificity↗
PubMed1983

Bone marrow transplantation in 33 patients with malignant blood diseases and severe aplastic anaemia.

Allogeneic bone marrow transplantation using HLA-identical sibling donors was performed in 29 patients with malignant blood diseases and in four patients with severe aplastic anaemia. Twenty-five patients received immunosuppressive therapy with cyclosporin A to minimize graft-versus-host disease (GVHD) and eight received methotrexate. Twenty-one of 29 patients (72%) with malignant blood diseases and three of the four patients with severe aplastic anaemia remained alive and disease-free from 0.5 to 16 (median, seven) months after transplantation. Acute GVHD, predominantly of the skin, occurred in 25 of 28 evaluable cyclosporin A recipients (of whom two died), and in all five evaluable methotrexate recipients. Mild chronic GVHD occurred in 10 of 16 evaluable patients. Interstitial pneumonitis occurred in five patients, of whom two died. HLA-identical sibling marrow transplantation is associated with a mortality similar to that of induction chemotherapy for acute leukaemia, and should be considered in adults with acute leukaemia in remission or relapse, chronic myelogenous leukaemia in metamorphosis or blastic transformation, lymphoma unresponsive to conventional therapy, and in severe aplastic anaemia.

Adolescent↗
PubMed1983

A monoclonal antibody recognizing HLA-DR2 on malignant and activated cells.

A monoclonal antibody, designated NDS15.38, which recognizes a polymorphic determinant of HLA-DR, was produced from a fusion in which mice were immunized with the human B lymphoblastoid cell line GIR2 (HLA type A1, B8, 27, Cw2, DR2,7). NDS15.38 functions efficiently as an affinity column and purifies a two-chain complex of molecular weight 33 000 and 30 000 under reducing conditions. The monoclonal antibody reacts with HLA-DR2-positive B lymphoblastoid cell lines and B lymphocytes from patients with chronic lymphatic leukemia in an indirect radioactive binding assay. However, NDS15.38 does not appear to react with peripheral blood B lymphocytes from normal individuals. Using a peroxidase staining technique, NDS15.38 was shown to react with phytohemagglutin (PHA)-stimulated lymphocytes and with apparently activated B cells in the germinal centers of lymph nodes from individuals who were tissue typed as HLA-DR2. Thus it appears that NDS15.38 recognizes a polymorphic determinant of HLA-DR on malignant and stimulated cells, but not on resting cells.

Animals↗
PubMed1983

Localization of major histocompatibility complex (HLA-ABC and DR) antigens in 46 kidneys. Differences in HLA-DR staining of tubules among kidneys.

Biopsies from 46 kidneys that were subsequently transplanted were examined with monoclonal antibodies and the peroxidase-antiperoxidase technique to localize HLA-ABC and DR antigens. There was no variation in the expression of HLA-ABC which was present on all cells of the renal parenchyma. HLA-DR was found consistently on the endothelium of glomeruli and of intertubular capillaries but was only weakly expressed, or not expressed at all, on the endothelium of large vessels. The mesangium of glomeruli also stained for HLA-DR. But there was a striking variation in the expression of HLA-DR by proximal renal tubular cells in the 46 kidneys. HLA-DR was absent from tubules in 11 of 46 kidneys (23%) and probably absent or very weakly expressed in a further 8 kidneys (17%). The expression of HLA-DR in tubular epithelium was not related to the donor's age, sex, blood group, or ischemia times. However, the frequency of HLA-DR3 increased (55%) in donors of kidneys with tubular DR-negative kidneys, as compared with a frequency of 15% in donors of tubular DR-positive kidneys. Although this difference was not significant after a correction for the number of comparisons made, it suggests a genetic influence on the expression of tubular DR. The survival of tubular DR-negative kidneys was better at 1 year than that of tubular DR-positive kidneys (70% vs. 57%--not significant), and tubular DR-positive grafts may have had a higher rate of delayed function when transplanted in cases with a donor-specific positive B cell crossmatch. There was no obvious variation in the number of dendritic cells stained with antibodies to HLA-DR and the leukocyte common antigen despite prior administration of high doses of steroids to some donors before nephrectomy.

Adolescent↗