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M Suthanthiran

Publications and source records attributed to M Suthanthiran.

155 records · Page 9Linked to original sources
PubMedDate not supplied

Hydroxyl radical scavengers inhibit human natural killer cell activity.

As natural killer (NK) cell activity is an essential constituent of host defence systems and reactive oxygen intermediates participate in such defence, the effect of scavengers of oxygen radicals on NK cell activity was investigated. Hydroxyl radical (OH) scavengers (dimethyl sulphoxide (DMSO), thiourea, dimethylurea, tetramethylurea, benzoic acid, ethanol, methanol and ethylene glycol) inhibited NK cell activity. Catalase, a scavenger of H2O2, and superoxide dismutase (SOD), a scavenger of O-2, either alone or in combination, did not inhibit NK cell activity. Inhibition of the lipoxygenase pathway of arachidonic acid metabolism, a potential source of cellular OH, with nordihydroguaiaretic acid and 5,8,11,14-eicosatetraynoic acid (ETYA) resulted in marked inhibition of NK cell activity. Inhibition of the cyclooxygenase pathway with acetylsalicylic acid or indomethacin had minimal effects on NK cell activity. Taken together, these findings suggest that OH, possibly generated via the lipoxygenase pathway of arachidonic acid metabolism, is critical for NK cell cytotoxicity.

Arachidonic Acids↗
PubMedDate not supplied

Cellular and humoral mechanisms in the pathogenesis of tubulointerstitial nephritis.

Brown-Norway (BN) rats immunized with renal medulla from Sprague-Dawley (SD) rats developed a renal lesion characterized by focal interstitial and perivascular mononuclear cell infiltrates without glomerular involvement. The cellular infiltrates were extracted from the affected kidneys and determined to consist of monocytes 64 +/- 4% (mean +/- S.D.) and T cells 2 +/- 9%. IgG antibodies directed at tubular basement membrane and tubular cell antigens were found in the affected kidneys and in circulation. Sera of immunized rats were used in in vitro studies to determine the presence of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In the CDC there was cytolysis of SD kidney and spleen cells but not BN kidney cells. In the ADCC there was significant lysis of BN kidney cells as well as SD kidney cells. Antibodies have been raised in the immunized rats against major histocompatibility (MHC) antigens as well as against autologous tubular cells. The finding of monocytes bearing Fc receptors among the infiltrating cells, as well as antibodies that can function in an ADCC indicates the presence of a combined immune effector mechanism that might be operative in tubulointerstitial nephritis.

Animals↗
PubMedDate not supplied

Induction of donor-specific immune modulation and successful renal transplantation with a simplified method of donor-specific blood transfusion.

We developed a new method of donor-specific blood transfusion (DST) for prospective kidney transplant recipients from a living related donor. Forty-four patients were transfused with 100 ml of one-haplotype matched kidney donor's whole blood at 1, 8, and 15 days after its storage. Ten of these patients received azathioprine (1.5 mg/kg per day) in addition to DST. After DST, three patients (6.8%) developed donor-specific lymphocytotoxic antibodies. The incidence of sensitization was not different between azathioprine-treated and untreated patients. Following DST, donor-specific mixed lymphocyte culture (MLC) was significantly suppressed without any accelerated (secondary type) response in early MLC. Subsequently, 24 patients received a kidney transplant from the donor. Graft survival rates were 96% and 90% at 12 and 24 months, respectively. Nine additional patients, seven from a two-haplotype matched sibling and two from a no-haplotype matched sibling also received DST. None of these patients became sensitized following DST, and all have functioning grafts for 6 to 18 months. This study indicates that 100 ml of stored whole blood DST three times at weekly intervals is a practical, less immunizing, and effective approach to enhance graft survival in recipients of a living related donor graft, DST produces donor-specific adaptive responses that might be conductive to successful graft outcome, and this protocol could be used in sibling donor-recipient pairs who do not share a haplotype.

Adult↗