Platelets in Early Antibody-Mediated Rejection of Renal Transplants

Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses.     

Gentamicin-induced diffuse renal tubular dysfunction.

Sir, Aminoglycoside-induced renal tubular dysfunction could be dividedinto Fanconi-like syndrome (FS) and Bartter-like syndrome (BS)[1]. The risk factors and mechanisms of tubular dysfunctionare little known. Here, we report a case of gentamicin-inducedFS, BS and distal renal tubular acidosis (RTA) and propose thepossible involvement of mitochondria. Case. A 66-year-old Chinese male was admitted because ofpneumonia.     

Sternum insufficiency fracture presenting as acute chest pain: a case report and review of the literature.

The spine, pelvic bones and long bones of the lower extremities are common sites for insufficiency fractures. Cases of sternum insufficiency fractures have been rarely reported in an elderly patient. Insufficiency fracture tends to occur in bones with decreased mechanical strength. It tends to occur in elderly patients, especially in postmenopausal women, with underlying diseases. We describe a case of sternum insufficiency fracture in a patient with rheumatoid arthritis and systemic lupus erythematosus on long-term corticosteroid therapy diagnosed in an emergency setting. Sternum insufficiency fracture is a rare cause of chest pain. This case serves to remind the emergency physician to remain vigilant for other noncardiac and nontraumatic causes of chest pain. If diagnosed accurately, these patients can be discharged and treated as outpatients.     

Oral and dental manifestations in diabetic and nondiabetic uremic patients receiving hemodialysis.

OBJECTIVE: The aim of this study was to examine the dental condition and oral manifestations in diabetic and nondiabetic uremic patients undergoing hemodialysis. STUDY DESIGN: A total of 128 patients undergoing hemodialysis therapy were classified into the diabetic and nondiabetic groups and examined for uremic oral manifestations, dental caries, and the periodontal status. All the patients received predialytic salivary pH examination. In the diabetic group, the correlation between oral findings and glycemic controlled levels, which was collected based on Hb A1C values, were further studied. RESULTS: The diabetic group exhibited significantly higher prevalence of caries and more severe dry mouth, taste change, and mucosa pain than the nondiabetic group. The diabetic group tended to have lower predialytic salivary pH, and patients with poor glycemic control (ie, Hb A1C > 9%) showed higher incidence of dry mouth, mucosal pain, and tongue coating. However, the DMFT and CPI index were not associated with glycemic control in the diabetic group. CONCLUSIONS: This study reveals that diabetic uremic patients undergoing maintained hemodialysis exhibited a potentially higher risk for dental decay and xerostomia. Lower salivary pH and poor glycemic control may affect oral manifestations. Further research is needed to clarify the combined influence of diabetic nephropathy on oral health.     

Reduced expression of CD69 and adhesion molecules of T lymphocytes in asthmatic children receiving immunotherapy

T lymphocytes play a fundamental role in the initiation and regulation of chronic inflammatory responses in patients with asthma. CD69 is an early marker of T‐cell activation. The levels of intercellular adhesion molecule‐1 (ICAM‐1, CD54) and L ‐selectin have been reported to increase in patients with allergic diseases and asthma. The present study was therefore undertaken to investigate the expression of CD69, CD54, and L ‐selectin by T lymphocytes of children with asthma, before and after immunotherapy. Eighteen children newly diagnosed with asthma, 11 good and nine poor responders to immunotherapy, and 16 normal subjects, were enrolled in this study. The percentages of CD69⁺, CD54⁺, and CD62L⁺ cells in T lymphocytes were measured by using flow cytometry. The levels of CD69, CD54, and CD62L in serum and culture supernatants were determined by using enzyme‐linked immunosorbent assay (ELISA). The expression of CD69 and CD54 on CD3⁺ T lymphocytes was significantly higher in children with asthma than in control patients. All the patient groups expressed (spontaneously and following stimulation with phorbol myristate acetate and ionomycin together with mite‐extract proteins) greater amounts of CD69 and CD54 than did control subjects. With long‐term immunotherapy, the percentages of CD69⁺ and CD54⁺ T lymphocytes were significantly lower in patients with a good response to immunotherapy. Our results also showed significantly lower serum L ‐selectin levels following immunotherapy. In conclusion, successful immunotherapy resulted in decreased expression and production of CD69 and CD54. These results may explain, in part, the clinical efficacy of immunotherapy.     

Antiproliferative effects of A02011-1, an adenylyl cyclase activator, in cultured vascular smooth muscle cells of rat.

1. The effects of A02011-1, a pyrazole derivative, on the proliferation of rat vascular smooth muscle cells (VSMCs) were examined. 2. A02011-1 (1-100 microM) concentration-dependently inhibited [3H]-thymidine incorporation into DNA in rat VSMCs that were synchronized by 48 h serum depletion and then re-stimulated by addition of foetal calf serum (FCS, 10%), platelet-derived growth factor (PDGF, 10 ng ml-1), 5-hydroxytryptamine (10 microM) or ADP (10 microM). The inhibitory effect of A02011-1 was fully reversible. However, FCS-induced [3H]-thymidine incorporation into rat endothelial cells was unaffected by A02011-1. 3. The concentration of A02011-1 necessary for inhibition of the FCS-induced proliferation was similar to that necessary for adenosine 3':5'-cyclic monophosphate (cyclic AMP) formation. Adenylyl cyclase activity was increased in A02011-1-treated VSMCs, whereas cyclic AMP-specific phosphodiesterase activity was unchanged. 4. A02011-1 was equipotent with forskolin but was more potent than 8-bromo-cyclic AMP against FCS (10%)-induced proliferation. 5. The antiproliferative action of A02011-1 was mimicked by 8-bromo-cyclic AMP, a membrane-permeable cyclic AMP analogue and was antagonized by 2',5'-dideoxyadenosine, an adenylyl cyclase inhibitor and by Rp-cyclic AMPS, a competitive inhibitor of cyclic AMP-dependent protein kinase (PKA) type I and II. 3-Isobutyl-1-methylxanthine (IBMX) caused significant potentiation of the antiproliferative activity of A02011-1. However, Rp-8-bromo-cyclic GMPS and staurosporine did not affect the antiproliferative activity of A02011-1.(ABSTRACT TRUNCATED AT 250 WORDS)