Ultraviolet-B irradiation of platelets: a preliminary trial of efficacy

Prior studies established that ultraviolet-B light (UVB) irradiation of platelet concentrates (PCs) at appropriate doses can eliminate the mixed lymphocyte culture-stimulating and -responding capacity of lymphocytes in the PCs without adversely affecting in vitro platelet function. The in vivo recovery and survival and in vitro characteristics of UVB-irradiated platelets were investigated in paired studies. PCs were stored for 1 day and then exposed to UVB. Platelet recovery, survival, and function were comparable to those of nonirradiated platelets. Recovery and survival of platelets stored for 5 days before UVB exposure were decreased relative to controls, although they were considered clinically acceptable. Paired transfusion studies were also performed in seven thrombocytopenic patients by using platelets obtained by apheresis. Comparable posttransfusion platelet increments and bleeding time corrections were obtained with both irradiated and control (nonirradiated) platelets. It can be concluded that platelets survive and function relatively normally in vivo after UVB irradiation sufficient to abolish lymphocyte reactivity in mixed lymphocyte culture. Long-term studies of UVB-irradiated PCs are needed to assess their potential in reducing recipient alloimmunization.     

Donor screening for antibody to hepatitis B core antigen and hepatitis B virus infection in transfusion recipients

BACKGROUND: Testing for antibody to hepatitis B core antigen (anti-HBc) as a surrogate for hepatitis C viremia is no longer needed for blood donor screening. Currently, the important question is how much its use supplements hepatitis B surface antigen (HBsAg) donor screening in preventing transfusion-transmitted hepatitis B virus (HBV) infection. STUDY DESIGN AND METHODS: In a study conducted in the 1970s, 64 blood donors were associated with 15 cases of HBV (1.0%) in 1533 transfusion recipients. Sera from 61 donors at donation and 29 follow-up visits were available for present-day assays for HBsAg, HBV DNA, anti-HBc, and antibody to HBsAg (anti-HBs). RESULTS: HBsAg was found in four previously negative blood donors; HBV DNA was limited to three of these four. Anti-HBc was detected in six HBsAg-negative donors. Two other donors were negative in all assays at donation, but positive for anti- HBc and anti-HBs 2 to 4 months later. The remaining donors were negative for all HBV markers, which left five recipient cases unexplained. No HBV transmission was observed when anti-HBs sample-to- negative control values were > or = 10. CONCLUSION: Some 33 to 50 percent of cases of hepatitis B that could be transmitted by transfusion of blood from HBsAg-negative donors are prevented by anti- HBc screening. Anti-HBc-positive donors unequivocally positive for anti- HBs should be considered noninfectious for HBV and should be allowed to donate. Anti-HBc screening of paid plasmapheresis donors, supplemented by anti-HBs testing, would reduce the amount of HBV to be processed by virus inactivation and increase the content of anti-HBs in plasma pools.     

Macrolide resistance mechanisms among Streptococcus pneumoniae isolated over 6 years of Canadian Respiratory Organism Susceptibility Study (CROSS) (1998 2004)

BACKGROUND: Resistance to macrolides in Streptococcus pneumoniae arises primarily due to Erm(B) or Mef(A). Erm(B) typically confers high-level resistance to macrolides, lincosamides and streptogramin B (MLS(B) phenotype), whereas Mef(A) confers low-level resistance to macrolides only (M phenotype). The purpose of this study was to investigate the incidence of macrolide resistance mechanisms in Canadian isolates of S. pneumoniae obtained between 1998 and 2004. Furthermore, the genetic relatedness, serotype distribution and antibiotic susceptibility profile among S. pneumoniae isolates with dual erythromycin ribosomal methylase [Erm(B)] and efflux pump [Mef(A)] were analysed. METHODS: A total of 865 macrolide-resistant (erythromycin MIC > or = 1 mg/L) S. pneumoniae isolates were collected from the Canadian Respiratory Organism Susceptibility Study (CROSS) from 1998 to 2004. The presence of erm(B) and mef(A) was determined for each isolate by PCR; mutations in the genes coding for L4 and L22 ribosomal proteins and for 23S rRNA were identified by DNA sequencing. Each isolate containing both erm(B)- and mef(A)-mediated macrolide resistance was genotyped by PFGE and serotyped using the Quellung reaction with antisera. RESULTS: Of the 865 isolates studied, 404 (46.7%) were mef(A)-positive, 371 (42.9%) were erm(B)-positive, 50 (5.8%) were positive for both mef(A) and erm(B) and 40 (4.6%) were negative for both mef(A) and erm(B). Of the macrolide-resistant isolates negative for both mef(A) and erm(B), 22 (2.5%) contained 23S rRNA A2058G, A2059G or A2059C mutations, 7 (0.8%) contained 23S rRNA A2058G or A2059G mutations along with an S20N mutation in L4 ribosomal protein, and 1 isolate contained an E30K ribosomal protein mutation alone. Of the macrolide-resistant strains positive for both mef(A) and erm(B), 36 (72%) were multidrug-resistant (macrolide-, penicillin- and trimethoprim/sulfamethoxazole-resistant), 39 (78%) isolates belonged to serotype 19A or 19F and 36 (72%) belonged to one clonal complex (> or =80% genetic relatedness) genetically related to the Taiwan 19F-14 clone. CONCLUSIONS: The prevalence of efflux-based macrolide resistance in S. pneumoniae in Canada remained steady between 1998 and 2004. Macrolide resistance due to erm(B) decreased over the same time period, with a rapid increase in isolates with both erm(B) and mef(A) macrolide resistance.     

Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors

BACKGROUND: This study evaluated the usefulness of the serologic test for syphilis (STS) in preventing the transmission of human immunodeficiency virus (HIV), hepatitis B and C viruses, and human T- lymphotropic virus via the transfusion of seronegative, infectious window-period blood. STUDY DESIGN AND METHODS: Demographic and laboratory information on blood donations made between January 1992 and June 1994 in 18 American Red Cross regions was analyzed. It was assumed that the same proportion of HIV-positive and HIV-infectious window- period donations reacted on STS and were negative on other screening tests (hepatitis B and C viruses and human T-lymphotropic virus). This proportion multiplied by the estimated number of HIV-infectious window- period donations is the number of post-screening HIV-infectious donations removed by STS. RESULTS: Of 4,468,570 donations, 12,145 (0.27%) were STS positive and 377 (0.008%) were HIV positive. Among donations that were negative on other screening tests, STS-reactive donations were 12 times more likely to be HIV positive (odds ratio = 11.9; 95% CI = 5,26). However, of an estimated 13 infectious window- period donations, 0.2 would have been removed because of a reactive STS, at a cost of over $16 million. CONCLUSION: STS is a poor marker and a costly strategy for preventing post-screening HIV infections and other blood-borne diseases.     

Molecular epidemiology and prevalence of macrolide efflux genes mef(A) and mef(E) in Streptococcus pneumoniae obtained in Canada from 1997 to 2002

One hundred forty M phenotype Streptococcus pneumoniae isolates were evaluated by PCR-restriction fragment length polymorphism, serotyping, and pulsed-field gel electrophoresis. Molecular genotyping revealed that the predominant macrolide resistance mechanism in S. pneumoniae in Canada is mef(E) and resistance dissemination is due to both spread of the genetic element MEGA as well as clonal dissemination of penicillin- and/or macrolide-resistant strains.     

Adaptive differentiation of murine lymphocytes. IV. (Responder × Nonresponder) F(1) T cells can be taught to preferentially help nonresponder,rather than responder, B cells

Responses to the synthetic terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT) in the mouse are controlled by H-2-1inked Ir-GLTgenes. (Responder × nonresponder) F(1) hybrid mice, themselves phenotypic responders, can be primed with GLT to develop specific helper cells capable of interacting with 2,4-dinitrophenyl hapten (DNP)-primed F(1) B cells in response to DNP-GLT. Unlike the indiscriminant ability of F(1) helper T cells for conventional antigens (i.e. not Ir gene-controlled), which can help B cells of either parental type (as well as F(1)) equally well, GLT-primed F(1) T cells can only provide help under normal circumstances for B lymphocytes of responder parent origin; they are unable to communicate effectively with nonresponder parental B cells (1, and the present studies). The present studies reveal, however, that the induction of a parental cell-induced allogeneic effect during priming of F(1) mice to GLT actually dictates the direction of cooperating preference that will be displayed by such F(1) helper cells for B cells of one parental type or the other. Thus, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by parental BALB/c cells, develop into effective helpers for nonresponder A/J B cells, but fail to develop effective helpers for responder BALB/c B cells, and vice-versa. In contrast, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by either parental type, display significantly enhanced levels of helper activity for B cells derived from F(1) donors. These results are interpreted to reflect the existence of two interdependent events provoked by the allogeneic effect: one event augments the differentiation of GLT-specific helper T cells belonging to the subset corresponding to the opposite parental type; this would explain the development of increased helper activity provided to partner B cells of opposite parental type (as well as of F(1) origin). The second event, we postulate, involves the production of responses against the receptors which normally self-recognize native cell interaction determinants; this form of anti-idiotype response is restricted against self- recognizing receptors of the same parental type used for induction of the allogeneic effect, hence explaining diminished helper activity of such F(1) cells for partner B lymphocytes of corresponding parental type.     

ALAS, our frailty is the cause … of a new for form of protoporphyria

C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload
Whatley et al. (2008)
The American Journal of Human Genetics 83: 408–414     

缺血性脑卒中的A-S-C-O(表型)分类

背景和目的:国际5国脑血管病专家提出一种新的腩卒中亚型分类法,旨在介绍完整的"脑卒中表型"分类的新观念,该分类是包括脑卒中的病因和存在的所有病因相关的疾病,并将病因疾病按严重程度分成3级.