Dopaminergic modulation of synaptic plasticity in rat prefrontal neurons

The prefrontal cortex(PFC) is thought to store the traces for a type of long-term memory – the abstract memory that determines the temporal structure of behavior often termed a "rule" or "strategy". Long-term synaptic plasticity might serve as an underlying cellular mechanism for this type of memory. We therefore studied the induction of synaptic plasticity in rat PFC neurons, maintained in vitro, with special emphasis on the functionally important neuromodulator dopamine. First, the induction of long-term potentiation(LTP) was facilitated in the presence of tonic/background dopamine in the bath, and the dose-dependency of this background dopamine followed an "inverted-U" function, where too high or too low dopamine levels could not facilitate LTP. Second, the induction of long-term depression(LTD) by low-frequency stimuli appeared to be independent of background dopamine, but required endogenous, phasically-released dopamine during the stimuli. Blockade of dopamine receptors during the stimuli and exaggeration of the effect of this endogenouslyreleased dopamine by inhibition of dopamine transporter activity both blocked LTD. Thus, LTD induction also followed an inverted-U function in its dopamine-dependency. We conclude that PFC synaptic plasticity is powerfully modulated by dopamine through inverted-U-shaped dose-dependency.     

Evaluating breast cancer predisposition genes in women of African ancestry

PurposeStudies conducted primarily among European ancestry women reported 12 breast cancer predisposition genes. However, etiologic roles of these genes in breast cancer among African ancestry women have been less well-investigated.MethodsWe conducted a case-control study in African American women, which included 1117 breast cancer cases and 2169 cancer-free controls, and a pooled analysis, which included 7096 cases and 8040 controls of African descent. Odds ratios of associations with breast cancer risk were estimated.ResultsUsing sequence data, we identified 61 pathogenic variants in 12 breast cancer predisposition genes, including 11 pathogenic variants not yet reported in previous studies. Pooled analysis showed statistically significant associations of breast cancer risk with pathogenic variants in BRCA1, BRCA2, PALB2, ATM, CHEK2, TP53, NF1, RAD51C, and RAD51D (all P < .05). The associations with BRCA1, PALB2, and RAD51D were stronger for estrogen receptor (ER)-negative than for ER-positive breast cancer (P heterogeneity < .05), whereas the association with CHEK2 was stronger for ER-positive than for ER-negative breast cancer.ConclusionOur study confirmed previously identified associations of breast cancer risk with BRCA1, BRCA2, PALB2, ATM, TP53, NF1, and CHEK2 and provided new evidence to extend the associations of breast cancer risk with RAD51C and RAD51D, which was identified previously in European ancestry populations, to African ancestry women.     

四肢关节专用低场强MRI评估对膝关节损伤的诊断价值

目的：分析四肢关节专用低场强MRI诊断膝关节损伤的临床应用价值。 方法：于2004-12/2005-10解放军总医院全军骨科研究所收治经手术、关节镜检查或临床证实的膝关节损伤患者40例（43个膝关节）。应用Atorscan0.2T永磁型四肢关节专用低场强磁共振机,对膝关节损伤的MRI表现进行分析。 结果：四肢关节专用低场强MRI对半月板、前交叉韧带、骨挫伤等均可作出正确诊断。 结论：四肢关节专用低场强MRI对膝关节损伤的综合诊断具有重要意义,是膝关节损伤较理想的一种非创伤性检查方法。     

人脂肪干细胞复合脱细胞软骨基质支架在生物反应器中构建组织工程软骨

目的:观察人脂肪干细胞复合脱细胞软骨基质支架在生物反应器中初步构建组织工程软骨的可行性。方法:实验于2005-04/2006-05在解放军总医院骨科研究所完成。脂肪组织和关节软骨均来自膝关节置换术中切除的组织,并经患者知情同意。关节软骨冻干后经粉碎机粉碎,过筛,选取25～38μm大小的软骨微粒。在样品中先加入2.5g/L胰蛋白酶,37℃消化24h,再加入1%Triton X-100震荡72h。将软骨微粒和蒸馏水按1∶3的比例混合后滴加在模板中,置入冷冻干燥机冻干后行紫外线交联。紫外线照射8h完成。最后经25kGy 60Co辐照灭菌完成支架制备。取膝关节置换术中切除的髌下脂肪垫,酶消法获得脂肪干细胞,扩增后复合于脱细胞软骨基质制成圆柱状三维支架上(细胞密度5×1010L-1),置于生物反应器中进行诱导培养,同时设静态培养组作为对照,3周后观测大体形态和组织学形态变化,同时进行组织化学(包括番红花O,阿利新蓝染色)和Ⅱ型胶原免疫组织化学分析。结果:生物反应器组诱导培养3周苏木精-伊红染色显示支架结构消失,只有中心区域残存少量支架结构;静态培养组支架结构尚存在,有少量基质分泌。番红花O染色显示生物反应器组细胞外有大量蛋白聚糖沉积,阿利新蓝染色表明有软骨特异性蛋白多糖的聚集;而静态培养组只有部分区域染色且淡于生物反应器组。Ⅰ型胶原免疫组化的结果显示,在生物反应器组细胞能够合成大量软骨细胞特异性胶原成分,而静态培养组呈弱阳性。结论:生物反应器培养明显促进了脂肪干细胞的增殖与软骨分化,是体外构建组织工程软骨的良好方法。     

Percutaneous umbilical blood sampling and umbilical vein transfusions. Rapid serologic differentiation of fetal blood from maternal blood

Percutaneous umbilical blood samples (PUBS), obtained under ultrasound guidance, are used for prenatal diagnosis and management of hemolytic disease of the newborn (HDN) and other fetal disorders. Rapid testing at the time of sampling is vital to distinguish fetal from maternal blood. Blood typing was performed by slide technique in the treatment room during 38 procedures on 25 patients. Anti-I was used to test 50 presumed PUBS; venous I-positive maternal blood was tested in parallel. Because anti-I cannot detect fetal blood after umbilical vein transfusion (UVT) of I-positive donor blood, ABO and Rh blood typing reagents were used to test 29 samples when maternal and fetal or donor blood groups differed. Monoclonal reagents were used for optimal detection of weak AB antigens in fetal blood. Avid, chemically modified anti-D was used for Rh typing. Blood typing showed 27 (34%) of 79 samples to be maternal blood. Fetal blood was obtained in 8 of 10 cases investigated for fetal disorder and in 16 cases of potential HDN (anti-D, 5; -CD, 5; -cE, 2; -K, 2; -c; -E). The absence of HDN (antigen-negative fetus) was determined in 4 cases. UVT afforded live birth of 9 of 10 infants with HDN and was not indicated in two cases.     

Electronic verification of donor-recipient compatibility: the computer crossmatch

Background: This article describes standard operating procedures (SOPs) for a computer crossmatch to replace the immediate-spin crossmatch for ABO incompatibility between patient blood samples submitted for pretransfusion testing and the blood component selected for transfusion. These SOPs were developed following recent changes to the Standards for Blood Banks and Transfusion Services of the American Association of Blood Banks (AABB). Study Design and Methods: SOPs were developed, utilizing currently available software, for pretransfusion testing. The SOP for donor unit processing entails bar code entry of the unit number, component name, and ABO/Rh type; computer entry and interpretation of serologic reactions; warning of discrepancies between bar code-entered blood type and result interpretation; and quarantine of the donor unit in such instances. The SOP for patient sample testing requires bar code entry of specimen accession number, which accesses patient demographics; computer entry and interpretation of ABO/Rh tests; repeat blood typing at the time of crossmatch if only one patient blood type is on record; and warning if there are nonconcordant current and historical blood types. The computer crossmatch SOP requires bar code entry of specimen accession and donor unit numbers; release of group O red cells pending resolution of discrepancies; and immediate-spin crossmatch during computer downtime. Tables validated on- site prompt warning messages and prevent both computer crossmatch and release if blood components of the wrong ABO type are selected. Results: These SOPs meet the requirements of the 15th edition of the AABB Standards. Projected annual time savings at this institution are > 100,000 workload recording units. Further benefits include reduced patient sample volume requirements, less handling of biohazardous material, and elimination of unwanted positive or negative reactions associated with the immediate-spin crossmatch. Release of incompatible blood components when the wrong patient blood type is on record is addressed by requiring the use of group O red cells in the absence of two concordant blood types, one of which must be from a current sample. Conclusion: A combination of existing computer programs and carefully developed SOPs can provide a safe and efficient means of detecting donor-recipient incompatibility without performance of serologic crossmatch.     

Discrepancies in reverse ABO typing due to prozone

Three group O sera manifesting prozone in reverse ABO tests are reported. All were implicated in erroneous blood typing results. One sample failed to react with A1 red cells (RBCs) in immediate-spin (IS) tests, had anti-A and -B titers of 8192 and 2048, respectively, by indirect antiglobulin technique (IAT), and was from a diabetic patient; the parenteral administration of A substance present in porcine insulin is a possible cause of hyperimmunity in this case. The second sample was from the recipient of a single unit of group B fresh-frozen plasma; the serum anti-A and -B titers were 10,240 by IAT, but only weak reactions with A1 and B RBCs were noted in routine IS reverse typing tests; the hyperimmunity in the patient concerned was likely due to crossreacting anti-A, B stimulated by B-active glycoproteins and/or glycolipids in the transfused plasma. The third serum also had anti-A and anti-B IAT titers of 10,240 but did not react with A1 and B RBCs by IS; the hyperimmunity in this case may be related to sepsis from intestinal flora carrying A- and/or B-like antigens. These antibodies lysed A1 and/or B RBCs in tests incubated at room temperature (RT) and strongly agglutinated those RBCs by IS when diluted 10-fold with saline. The absence of the prozone phenomenon in tests with RBCs suspended in diluents containing EDTA is consistent with the previously published mechanism for anti-A prozone: namely, the steric hindrance of agglutination by the C1 component of human complement.(ABSTRACT TRUNCATED AT 250 WORDS)     

Can the reading for serologic reactivity following 37 degrees C incubation be omitted?

The need to detect antibodies that agglutinate and/or hemolyze red cells (RBCs) directly at 37 degrees C, but do not react in subsequently performed indirect antiglobulin tests (IATs), is of concern relative to the streamlining and automation of antibody detection methods. To determine incidence and significance of such reactions, data from 87,480 tests, which used low-ionic-strength saline, 10-minute incubation at 37 degrees C, and anti-IgG, were analyzed for unexpected antibodies. There were 3590 positive tests, of which 475 showed reactions at 37 degrees C but not in subsequently performed IATs (37 + IAT-). Of these, 196 reactions were due to autoantibodies or other factors usually considered insignificant with respect to the survival of transfused incompatible RBCs, 176 were due to alloantibodies of questionable clinical significance (M, Lea, P1, etc.), and 103 were associated with alloantibodies of potential clinical significance (63 E, 27 K, 5 Jka, 4 D, 3 cE, and 1 C). This latter reaction was seen in 72 patients, with two 37 + IAT-antibodies occurring in each of 3 patients. Of the 75 potentially significant 37 + IAT-antibodies, 57 were seen in patients recently exposed to homologous RBCs, 13 in patients with a history of transfusion and/or pregnancy, and 5 in patients with no known exposure to homologous RBCs. IAT reactivity was observed in subsequent samples with 27 of these antibodies. The predictive value of a 37 + IAT-test was 21.7 percent for a potentially significant antibody. The incidence was 0.12 percent of all tests for unexpected antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)