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Biomedical subjects

A Ting

Publications and source records attributed to A Ting.

At least 109 records · Page 6Linked to original sources

A controlled trial of cyclosporine in renal transplantation with conversion to azathioprine and prednisolone after three months.

Thirty-five patients given an HLA-DR-incompatible cadaver kidney that was diuresing immediately after transplantation were randomly allocated to treatment with cyclosporine alone for 3 months followed by conversion to azathioprine and prednisolone (AP), or to conventional treatment with AP. Although many patients had to be converted to AP before 90 days because of rejection requiring more than two treatment courses of high-dose i.v. methylprednisolone, 16 of 21 grafts were functioning at 3 months, and 12 of 14 grafts in the control group were functioning. However 3 further grafts were lost from chronic rejection in the control group, and none were lost from chronic rejection in the cyclosporine group. All but one patient on cyclosporine had depressed renal function, and in all these patients function improved on conversion to AP. This depression of renal function is attributed both to cyclosporine nephrotoxicity and to a low-grade rejection reaction, the latter suggesting that the addition of steroids to cyclosporine might be beneficial in some patients. The strategy of a three-month course of cyclosporine followed by conversion to AP provides satisfactory immunosuppression, and it may be of value if long-term side effects of cyclosporine emerge with further experience.

Adult↗

Successful transplantation with a positive T and B cell crossmatch due to autoreactive antibodies.

A total of 16 cadaver donor renal allografts have been performed in the presence of a positive T and B cell crossmatch due to autoantibodies. Fourteen of these patients were considered to be highly-sensitized, in that they had pregraft antibodies reacting with more than 85% of the lymphocyte panel. Ten of the 16 grafts are still functioning with follow-up times of between 3 and 66 months. Within the same time period three living related donor transplants were also performed with a positive T and B cell crossmatch due to autoantibodies. Two were from HLA-identical siblings and the other from his father. All three patients had pregraft antibodies reacting with 100% of the lymphocyte panel. All grafts are functioning normally between 9 and 48 months after transplantation. Autoreactive T and B cell antibodies are not damaging to renal allografts and recognition of these antibodies allows a significant number of patients to be successfully transplanted (with a positive crossmatch).

Antigen-Antibody Reactions↗

A rational approach to crossmatching blood for elective surgery.

A group-and-screen system was introduced for selected surgical procedures to improve the cost-effectiveness of the hospital blood transfusion service. The mean crossmatch-transfusion ratio for eleven procedures was 11.1 but fell to 3.3 after the change. The overall crossmatch-transfusion ratio in the hospital improved from 2.7 to 2.2 (p less than 0.001) and blood wastage by expiry fell from 12% to 5% (p less than 0.02). The mean age of blood being transfused also improved slightly from 12.3 days to 10.4 days (p less than 0.001). No problems have arisen from the group-and-screen system to date. It has led to improvement in the efficiency and cost-effectiveness of the hospital blood bank and resulted in fresher blood being transfused.

ABO Blood-Group System↗

Maternal cell-mediated immunity in pregnancy--lymphocyte responses of mothers and their non-pregnant HLA identical sisters to paternal HLA.

The mixed lymphocyte reactions (MLR) of normal pregnant women and their non-pregnant HLA identical sisters have been compared, using paternal and unrelated lymphocytes as stimulator cells. Primary and secondary responses were differentiated by studying 7 day MLR time courses. All responses were of a primary nature, with neither stimulation nor suppression of the maternal MLR. These data clearly demonstrate the absence of maternal cellular sensitization to fetal (paternal) HLA.

Fathers↗

Low dose oral prednisolone in renal transplantation.

Azathioprine and steroids (prednisone or prednisolone) form the basis of conventional immunosuppression after renal transplantation. Most of the morbidity in the early months after transplantation. Most of the attributed to steroids, which are normally give in high doses. The only justification for giving high doses is a historical one. For this reason a randomised controlled trial was carried out to compare the efficacy of high dose (39 patients) and low dose (33 patients) oral prednisolone, both in combination with azathioprine, in patients given cadaveric renal allografts. Patients were followed up for at least two years after the transplantation. Patient and graft survival were identical in the two groups and the morbidity associated with steroids was impressively lower in patients receiving a low steroid dose. Although the optimal dose of steroids is still unknown, there seems little justification for continued use of high doses of oral steroids with azathioprine after cadaveric renal transplantation.

Administration, Oral↗

Reciprocal effects of an inhibitory factor on catalytic activity and noncatalytic cGMP binding sites of rod phosphodiesterase.

In illuminated rod outer segment membranes, GTP and guanosine 5'-[beta, gamma-imido]triphosphate (p[NH]ppG) have reciprocal effects on cGMP phosphodiesterase (PDEase; 3':5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) activity and cGMP binding to noncatalytic sites on that enzyme. Two micromolar p[NH]ppG increased PDEase activity more than 2-fold while inhibiting cGMP binding more than 40%. Reduction of noncatalytic cGMP binding, which followed addition of p[NH]ppG, was not a result of PDEase activation. Both effects of p[NH]ppG were completely dependent on the presence of bleached rhodopsin. A heat-stable factor has been found to inhibit PDEase activity and also to stimulate cGMP binding to noncatalytic cGMP binding sites. Addition of p[NH]ppG reversed the effects of this factor on both PDEase activity and cGMP binding. During purification of this material, the activity peaks for both PDEase inhibition and activation of noncatalytic cGMP binding comigrated on both Blue Sepharose CL-6B column chromatography and sucrose density gradients centrifugation, suggesting that the same factor could be responsible for both inhibition of PDEase activity and enhancement of noncatalytic cGMP binding. Limited tryptic proteolysis of PDEase, which markedly reduced cGMP binding to the noncatalytic sites, and experiments using highly purified cAMP (free of cGMP) as substrate for PDEase showed that the binding of cGMP to noncatalytic sites was not required for the heat-stable inhibitory factor to inhibit PDEase activity. We discuss possible relationships between the regulation of PDEase and the binding of cGMP to noncatalytic sites.

3',5'-Cyclic-GMP Phosphodiesterases↗

HLA-A, B, C and HLA-DR antigens in extrinsic allergic alveolitis (budgerigar fancier's lung disease).

Twenty-three patients with extrinsic allergic alveolitis due to an allergy to inhaled budgerigar serum protein (budgerigar fancier's lung disease) were typed for HLA-A, B, C and HLA-DR antigens. Antigen frequencies were compared with those found in 154 healthy control subjects. No statistically significant variation in the frequency of any HLA antigen was detected. Exclusion of two patients who had concurrent coeliac disease, and subdivision of the population into those with acute and chronic disease, failed to reveal any significant association with an HLA specificity. A non-significant increase in B8-DR3 amongst the patients with acute disease was noted. Possible reasons for the apparent HLA associations previously reported by others for extrinsic allergic alveolitis are discussed.

Acute Disease↗

Genetic susceptibility to the development of retinopathy in insulin-dependent diabetics.

HLA types and blood glucose control were investigated in 127 insulin-dependent diabetics with different grades of severity of retinopathy. The means of all afternoon clinic blood glucose levels from the diagnosis of diabetes were 9.9 +/- 2.1 mmol/L for patients with no retinopathy, 11.8 +/- 2.1 mmol/L for patients with background retinopathy, and 12.4 +/- 2.1 mmol/L for patients with proliferative retinopathy (P less than 0.0001). HLA-DR4 was present in 61 of 87 patients (70%) with background or proliferative retinopathy and 21 of 39 (54%) with no retinopathy. The frequency of HLA-DR4 was lowest in patients with no retinopathy despite "poor control" (mean blood glucose greater than or equal to 11.5 mmol/L) and highest in those who had developed retinopathy despite "good control;" the frequencies of HLA-DR2 showed the reverse pattern. Mantel-Haenszel tests were used to calculate the odds ratios for the presence of retinopathy associated with "poor control" and with HLA-DR4, since each modified the effect of the other. The odds ratio for retinopathy associated with "poor control" was 6.7 (P less than 0.0001). The odds ratio with HLA-DR4 was 3.7 (P less than 0.005). When both risk factors were present, the odds ratio increased to 33.3 (P less than 0.0001). Genetically determined factors appear to influence susceptibility to retinopathy in insulin-dependent diabetics.

Adult↗

Bleomycin and talisomycin sequence-specific strand scission of DNA: a mechanism of double-strand cleavage.

Computer analyses of DNA sequencing data obtained using various restriction fragments of pBR 322 DNA indicate that a trinucleotide sequence (-Pyr-G-C-) is the most preferred site for cleavage by the antitumor antibiotic bleomycin A2. Talisomycin A, a structurally related bleomycin analog, cleaved at the sequences -G-T/A- most preferentially. However, the presence of a pyrimidine at the 5' side of guanine at the cleavage site did not increase the probability of that site being cleaved by talisomycin. Using denaturing and nondenaturing polyacrylamide gel analyses of the drug-DNA reaction products. The sites of both single- and double-strand breaks have been localized and differentiated. The results indicate that a major determinant for location of a site-specific double-strand break is the production of two closely spaced sequence-specific single-strand breaks by the drugs on opposite strands of the DNA. A four-base pair sequence is proposed for the optimal sequence for bleomycin-induced double-strand breaks.

Base Sequence↗

Cross-reactions of Ia antigens between mouse and man.

Murine alloantisera with specificity for the I-region of the MHC were found to cross-react with human B lymphocytes. By using antisera selected for subregion specificity and including monoclonal antibodies, antisera directed to I-E/Ck products were shown to have the greatest cross-reactivity with human cells. In the reciprocal direction, human anti-DRw alloantisera were also found to contain antibodies that reacted with murine B lymphocytes, and by using congenic strains this reaction was shown to be MHC restricted and was of the "Ia type." By studying appropriate intra-H-2 recombinant strains. The reactivity could be mapped to the 1-E subregion (especially to 1-Ek). In addition, antibodies to the murine 1-Ek subregion could specifically block the reaction of the two DRw antisera examined; whereas, anti-I-Ak antisera were without effect. These studies further highlight the unique cross-reactions between two highly polymorphic gene produces in mouse and man, and demonstrate that the 1-E subregion in the mouse codes for the most cross-reactive specificities.

Animals↗

Localization of HLA-ABC and DR antigens in human kidney.

Monoclonal antibodies to human monomorphic class I and class II major histocompatibility complex (MHC) determinants have been used with immunofluorescence and immunoperoxidase techniques, to localize these antigens in normal human kidneys. HLA-DR antigen was located in the glomeruli (probably on endothelium as well as the mesangium) and within the cells of cortical and medullary tubules. Dendritic cells in the renal interstitium stained brightly for the DR antigen and could be distinguished from the staining of capillary endothelium. The vascular endothelium of large vessels stained less densely for the HLA-DR antigen than for HLA-ABC antigens. The glomeruli stained intensely for the HLA-ABC antigens and diffuse staining of HLA-ABC antigens was also noted within renal tubular cells.

Animals↗

Powerful effect of HL-DR matching on survival of cadaveric renal allografts.

Matching for HLA-DR antigens seems to be an effective method of improving the survival rate of cadaveric donor renal allografts; this was shown in the analysis of 190 cadaver transplants in one unit. Patients receiving kidneys well-matched for HLA-DR (no incompatibilities) had a significantly better survival rate (85% at 1 year) than patients with 1 or 2 incompatibilities (64% and 56% respectively, at 1 year). This high survival rate of the DR matched grafts was not due to coincidental better matching of the HLA-A and B antigens. DR matching seems to improve graft survival even in patients who have never been transfused or not. Matching for the limited number of DR antigens mostly with a relatively high antigen frequency should simplify the matching procedure for selection of donor-recipient pairs in cadaveric transplantation.

Cadaver↗