ABO compatibility can influence the results of platelet transfusion. Results of a randomized trial

Sixty consecutive patients with untreated acute leukemia alternately received either ABO-matched or ABO-mismatched random-donor platelet transfusions prepared from pooled platelet concentrate stored for 1 to 3 days. Patients were assigned randomly to receive matched or mismatched platelets as their first transfusion, and the first four transfusions were analyzed. In 40 evaluable patients, there was no significant difference (paired t test) between the 10-minute posttransfusion corrected count increments (CCI) of the initial transfusions of matched and mismatched platelets. In contrast, the second matched transfusion was significantly better than the second mismatched transfusion. This effect of ABO compatibility was particularly pronounced in a subset of patients. Six patients in whom mismatched transfusions were consistently inferior to matched transfusions had either a significant increase in anti-A or -B isoagglutinin titers following the first transfusion or elevated titers before or at the conclusion of the study. Conversely, in five patients in whom there was no apparent effect of ABO mismatching, only one had an increase in isoagglutinin titer. Platelet survival was not altered as the ratio of 18-hour to 10-minute posttransfusion CCl was 0.6 for both matched and mismatched platelet transfusions. These data demonstrate that ABO compatibility can affect the results of random-donor platelet transfusions and that patients who experience poor increments from ABO-mismatched platelets may benefit from a trial of ABO-compatible platelets before the initiation of HLA-matched platelet transfusion.     

Studies on the mechanism of bacterial resistance to complement-mediated killing. II. C8 and C9 release C5b67 from the surface of salmonella minnesota S218 because the terminal complex does not insert into the bacterial outer membrane

The mechanism for consumption of terminal complement components and release of bound components from the surface of serum-resistant salmonella minnesota S218 was studied. Consumption of C8 and C9 by S218 occurred through interaction with C5b67 on the bacterial surface because C8 and C9 were consumed when added to S218 organisms previously incubated in C8-deficient serum and washed to remove all C5b67 on the bacterial surface because C8 and C9 were consumed when added to S218 organisms previously incubated in C8- deficient serum and washed to remove al but cell bound C5b67. Rapid release of (125)I C5 and (125)I C7 from the membrane of S218 was dependent on binding of C8 because (125)I C5 and (125)I C7 deposition in C8D serum was stable and was twofold higher in C8D than in PNHA, and addition of purified C8 or C8 and C9 to S218 previously incubated in C8D serum caused rapid release of (125)I C5 and (125)I C7 from the organism. Analysis by sucrose density gradient ultracentrifugation of the fluid phase from the reaction of S218 and 10 percent PNHS revealed a peak consistent with SC5b-9, in which the C9:C7 ratio was 3.3:1, but the NaDOC extracted bound C5b-9 complex sedimented as a broad peak with C9:C7 of less than 1.2:1. Progressive elution of C5b67 and C5b-9 from S218 but not serum-sensitive S. minnesota Re595 was observed with incubation in buffers of increasing ionic strength. Greater than 90 percent of the bound counts of (125)I C5 or (125)I C9 were released from S218 by incubation in 0.1 percent trypsin, but only 57 percent of (125)I C9 were released by treatment of Re595 with trypsin. These results are consistent with the concept that C5b-9 forms on the surface of the serum-sensitive S. minnesota S218 in normal human serum, but the formed complex is released and is not bactericidal for S218 because it fails to insert into hydrophobic outer membrane domains.     

THE SPECIFIC SELECTION OF RECIRCULATING LYMPHOCYTES BY ANTIGEN IN NORMAL AND PREIMMUNIZED RATS

Thoracic duct lymphocytes (TDL) from normal rats will restore a primary antibody response to sheep erythrocytes (SRBC) in irradiated recipients and cause a graft-versus-host reaction in F₁ hybrid rats; lymphocytes from rats immunized with either tetanus toxoid or dinitrophenylated bovine gamma globulin (DNP BGG) will generate specific antibody after cell transfer and challenge. The ability of TDL to mediate each of these responses is severely depressed by giving a single intravenous dose of the specific antigen shortly before cannulation of the thoracic duct, although the lymphocyte donors themselves respond normally. The injection of antigen does not decrease the output of lymphocytes in the thoracic duct and the effect is specific for the antigen injected. The findings are most readily accounted for by assuming that small subpopulations of specific lymphocytes are selected from the recirculating pool by antigen which has localized in lymphoid tissue. The observation that passive antibody abolishes selection by SRBC supports this interpretation. The strong selection exerted by a subcutaneous injection of SRBC in Freund's complete adjuvant, which induces delayed hypersensitivity but little early antibody, suggests that a common cell type may be involved in the induction of both delayed hypersensitivity and antibody formation. The anti-DNP antibody response generated by TDL from rats immunized with DNP BGG was abolished by a selecting injection of the homologous conjugate. The response was depressed to a smaller degree by injections of either BGG or dinitrophenylated human serum albumin, suggesting that carrier-specific (T) and hapten-specific (B) lymphocytes could be separately selected from the recirculating pool. The regional selection of recirculating lymphocytes by antigen may explain a number of phenomena in which the prior injection of antigen has been found to inhibit a subsequent immune response.     

Modulation of MAPK pathways and cell cycle by replicating hepatitis B virus: factors contributing to hepatocarcinogenesis

BACKGROUND/AIMS: Chronic infection with the hepatitis B virus (HBV) is strongly associated with the development of hepatocellular carcinoma but the mechanism by which this occurs is unknown. Numerous studies have focused on the HBV X protein showing that it activates signal transduction pathways while few have investigated these changes in HBV-replicating hepatocytes. METHODS: We utilized the recombinant adenovirus system to deliver a replication competent HBV genome into Huh7 and primary marmoset hepatocytes (PMH) to examine the effects of active viral replication on the regulation of Ras-ERK signal transduction and related pathways. RESULTS: Huh7 cells and PMHs replicating HBV demonstrated significant upregulation in phosphorylated ERK, Akt, c-myc together with increased p53, cyclin B1 and p21(cip1) expression and cell cycle progression to G2 phase in the absence of increased cell proliferation. Phosphorylation of the key cell survival kinase, Akt, was significantly increased, resulting in increased serine phosphorylation of the downstream target, GSK3-beta. CONCLUSIONS: These results demonstrated simultaneous activation of the MAP Kinase and Akt pathways in HBV-replicating hepatocytes that resulted in dysregulation in the control of cell cycle progression and which help explain the early pathogenic mechanisms that underlie malignant transformation associated with chronic hepatitis B infection.     

幽门螺杆菌感染处理的当前观念——MaastrichtⅢ共识报告

名词缩写 欧洲幽门螺杆菌研究小组：European Helicobacter Study Group，EHSG 胃食管反流病：gastro-esophageal reflux disease，GERD     

Metastatic hepatocellular carcinoma with associated spinal cord compression

Metastatic hepatocellular carcinoma is a rare occurrence in the United States. The prognosis is poor, with a survival time of months from the time of diagnosis. This article reports a case of myelopathy that developed from metastases in a patient with no significant medical history. The patient was treated with decompressive laminectomy followed by adjuvant radiotherapy. A review of the literature demonstrated that most cases from hepatocellular carcinoma metastasizing to the spinal cord involve either the thoracic or lumbar levels and arise from the right liver lobe or both lobes. Major risk factors included positive hepatitis B virus serologies. This article also discusses current trends in management of epidural spinal cord compression. Although treatment with chemotherapy has not shown any benefit, surgical management has been shown to decrease morbidity and mortality in some patients.     

Treatment of water for dialysis ‐ A European survey

The EDTNA/ERCA survey of the treatment of water for dialysis was the third project organised through the Collaborative Research Programme (CRP). Data was collected from 69 haemodialysis facilities in 14 countries. Water quality in European dialysis units was mainly self‐regulated. The majority of centres aimed to meet the requirements of the European Pharmacopoeia, but only 50% carried out tests to check compliance. All facilities used reverse osmosis to treat water for dialysis, most also used softening and carbon adsorption. There was a wide variation in policies for the maintenance of carbon filters, and for the control and monitoring of contamination in the distribution system. Endotoxin tests carried out in 27 facilities showed that higher levels of contamination are associated with systems that are infrequently disinfected, and also with older system designs. The survey indicated that guidelines for water treatment are urgently needed. EDTNA/ERCA guidelines for microbiological monitoring are now being drafted, additional guidelines are under consideration.