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Biomedical subjects

A S Daar

Publications and source records attributed to A S Daar.

At least 91 records · Page 5Linked to original sources
PubMed1989

Chemical composition and tissue distribution of the human CDw44 glycoprotein.

The CDw44 glycoprotein was purified from 2.3 x 10(11) CD3+ CD4+ CD8- T-chronic lymphocytic leukaemia (CLL) cells using F10-44-2 monoclonal antibody affinity chromatography, DEAE-Sepharose anion-exchange chromatography, passage down carboxymethyl (CM)-Sepharose cation-exchange columns, wheat germ lectin affinity chromatography and gel-permeation chromatography. On elution in non-ionic detergents from the DEAE column, two distinct peaks of antigen activity were obtained. The CDw44 glycoprotein in each peak was a glycoprotein of 85,000 MW, but the amino acid composition of the peaks was noticeably different. Carbohydrate compositions showed that each peak contained approximately 30% (w/w) carbohydrate, the composition suggesting both O-linked and complex N-linked glycans. Modulation studies with the F10-44-2 antibody on normal peripheral blood mononuclear cells (PBMC) demonstrated that the CDw44 glycoprotein of T cells consisted of one fraction that was readily modulated, and the other which was resistant to modulation. Detailed tissue distribution studies for CDw44 were performed using the F10-44-2 antibody on frozen sections of human tissues. CDw44 has a restricted tissue distribution, but is found on many highly diverse cell types (e.g. T lymphocytes, smooth muscle cells, some secretory glands, skin epithelial cells).

Amino Acid Sequence↗
PubMed1988

Cyclosporine A versus cyclosporine G: a comparative study of survival, hepatotoxicity, nephrotoxicity, and splenic atrophy in BALB/c mice.

Our group has previously shown that cyclosporine A (CSA) but not cyclosporine G (CSG) causes splenic atrophy in a BALB/c mouse model. We have now extended our studies to observations of the effect of the two drugs on other parenchymal organs and on the nervous system. Groups of mice (N = 30) were given 150 mg/kg per day of either CSA or CSG and were compared to two control groups. Absorption of the drugs was similar in the two groups, although CSG blood levels were slightly higher. Animals treated with CSA, but not CSG, lost up to 50% of body weight over a 3-week period. Overall mortality was much higher in the CSA group. Blood urea levels were significantly higher in both treatment groups than in controls and were significantly higher in the CSA than in the CSG group. CSA-treated animals showed marked histological changes in their kidneys, the most prominent of which was proximal tubular vacuolation. Both drugs showed some hepatotoxicity, both histologically and biochemically; the histological changes were more marked in the CSA group. There was no pancreatic toxicity at this dose, either histologically or in terms of blood-sugar concentrations. Mice treated with CSA, but not with CSG, showed marked behavioral changes, including hyperactivity and irritability. The most intriguing observation was the effect of CSA, but not CSG, on the spleen. There was atrophy of lymphoid tissue in both the B and the T cell areas, although the most prominent change was in the periarterial lymphatic sheaths. These changes may be of significance in the long-term maintenance of immunosuppression and graft acceptance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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↗
PubMed1983

The membrane antigens of human colorectal cancer cells: demonstration with monoclonal antibodies of heterogeneity within and between tumours and of anomalous expression of HLA-DR.

The membrane antigens of fifteen colorectal tumours were studied using a number of monoclonal antibodies and the immunoperoxidase technique on frozen sections. With this approach we could easily demonstrate differences in the membrane structure of the cancer cells within the tumour mass of given patients and also readily demonstrate differences between tumours that were indistinguishable by histological and other standard criteria. An unexpected finding was the patchy expression of HLA-DR antigens on cancer cells, in spite of the absence of HLA-DR on normal colorectal epithelium. These findings have interesting theoretical and clinical implications.

Antibodies, Monoclonal↗
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↗
PubMed1981

Demonstration with monoclonal antibodies of an unusual mononuclear cell infiltrate and loss of normal epithelial membrane antigens in human breast carcinomas.

Monoclonal antibodies to two differentiation antigens normally expressed on the membranes of breast epithelial cells were used in immunofluorescence studies on frozen sections of malignant breast tumours. It was demonstrated that most tumours did not express these antigens on their cell membranes, and it was possible to classify histologically indistinguishable tumours according to whether they expressed the antigens. The absence of these membrane antigens is likely to be a subtle indicator of cellular differentiation and to have metabolic and other functional implications for the tumour. The demonstration that otherwise indistinguishable tumours can be classified in this way therefore has obvious potential for clinical exploitation. In addition, it was demonstrated that the majority of the mononuclear cells in those tumours with intense mononuclear cell infiltrates expressed an antigen not normally found on mature lymphocytes and macrophages.

Antibodies↗