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91.
Legitimizing surrogacy in Israel 总被引:3,自引:2,他引:1
Recently the Israeli Parliament passed legislation regarding all aspects of
assisted reproductive techniques, including surrogacy. The main points of
this legislation are presented and discussed. The most important aspects
are: (i) a public committee authorizes and supervises every single case;
(ii) only full surrogacy is permitted; (iii) the agreement is not
commercial, reasonable expenses can be paid to the surrogate mother under
the supervision of the Approving Committee; (iv) the surrogate mother must
be single or divorced; (v) under certain conditions the surrogate mother
can withdraw from the agreement; (vi) the child is under the tutelage of a
social worker, representing the state, from birth until the completion of
the adoption procedure. The religious, social and legal status of surrogate
pregnancies worldwide are discussed.
相似文献
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Medical students and residents have shown increasing interest in international health experiences. Before attempting to establish a global health training program in a family medicine residency, program faculty must consider the goals of the international program, whether there are champions to support the program, the resources available, and the specific type of program that best fits with the residency. The program itself should include didactics, peer education, experiential learning in international and domestic settings, and methods for preparing learners and evaluating program outcomes. Several hurdles can be anticipated in developing global health programs, including finances, meeting curricular and supervision requirements, and issues related to employment law, liability, and sustainability. 相似文献
95.
Progressive platelet activation with storage: evidence for shortened survival of activated platelets after transfusion 总被引:14,自引:0,他引:14
HM Rinder ; M Murphy ; JG Mitchell ; J Stocks ; KA Ault ; RS Hillman 《Transfusion》1991,31(5):409-414
Platelets are known to become activated during storage, but it is unclear whether such activation affects recovery or survival after platelet concentrate (PC) transfusion. With the use of flow cytometry to determine the percentage of platelets expressing the alpha-granule membrane protein 140 (GMP-140), a known adhesive ligand appearing on the platelet surface after activation, several studies were conducted. These investigations evaluated 1) the occurrence of significant platelet activation over time in PCs (n = 46) stored under standard blood bank conditions; 2) the correlation between platelet activation and platelet recovery in normal subjects after PC storage (n = 12), as assessed by the recovery of Indium-labeled platelets; and 3) the recovery of activated and unactivated platelets in thrombocytopenic cancer patients transfused with standard PCs (n = 11). It was determined 1) that an increasing duration of storage of PC was associated with increasing platelet activation as measured by the percentage of platelets expressing GMP-140, progressing from a mean of 4 +/- 2 percent (SD) on the day of collection to a mean of 25 +/- 8 percent by 5 days of storage: 2) that, in normal subjects, posttransfusion recovery of autologous platelets stored for 2 to 4 days and then labeled with In111 was inversely correlated with the percentage of activated platelets in the transfused PC (r = -0.55, p = 0.05); and 3) that, when thrombocytopenic patients were transfused with standard PCs, the recovery of the activated platelets in the transfused PCs averaged only 38 +/- 15 percent of the number predicted by the absolute platelet increment.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
96.
Clonal rearrangements of the Ig heavy chain (IGH) locus occur in nearly all cases of B-cell precursor acute leukemia (BCP-ALL). Some of these rearrangements may be detected by polymerase chain reaction (PCR) using VH gene framework III (FRIII) and JH consensus primers. However, about 20% of BCP-ALLs fail to amplify with this technique. To determine the causes of these PCR failures and to investigate any possible association with specific subgroups of disease, we analyzed 72 acute leukemias of defined immunophenotype and cytogenetics, comparing FRIII with VH-family leader-specific PCR methods and Southern blotting. Of 37 BCP-ALL cases, 6 (16.2%) failed totally to amplify with FRIII and JH primers. None of these cases amplified with VH leader primers. Additionally, all cases retained germline VH6 genes and 5 of 11 rearranged alleles amplified with a consensus DH primer, indicating that these rearrangements represented biallelic DH-JH recombinations. Among the 6 FRIII and VH leader PCR-negative BCP-ALL cases, there was no common immunophenotype or consistent cytogenetic abnormality, although all showed structural chromosomal abnormalities and 3 of 5 successfully karyotyped had abnormalities of chromosome 12p. 13 cases with t(9;22)(q34;q11) Philadelphia chromosome-positive [Ph+]) and IGH rearrangements (9 BCP-ALL and 4 biphenotypic cases) were also analyzed. Of 23 rearranged IGH alleles, 19 (82%) were positive by FRIII PCR, and all 4 remaining alleles were amplified by VH leader primers. Use of the leader primers in these Ph+ cases also detected 3 additional clonal rearrangements that were not anticipated from Southern blotting; such unexpected bands were not observed in 21 other Ph- cases. The additional bands represented "new" and unrelated VH rearrangements rather than VH-VH replacement events. We conclude that biallelic DHJH rearrangements occur in a subgroup of BCP-ALL; in these cases, the activation of the full VHDHJH recombination mechanism had not occurred. Therefore, these cases of BCP-ALL were arrested at an early stage of B- cell differentiation. In contrast, all Ph+ BCP-ALLs and biphenotypic acute leukemias, which may represent the transformation of multipotent hemopoietic stem cells, had undergone VHDHJH recombination. Of 9 Ph+ BCP-ALL cases, 3 also showed ongoing VHDHJH rearrangement, reflecting the persistent expression of the VHDHJH recombinase. Finally, sequence analysis of 33 rearranged VHDHJH genes showed that only 3 including 2 Ph+ BCP-ALL maintained an intact open-reading frame. Loss of the open- reading frame occurred not only because of out-of-frame VHDH and DHJH joining, but also because of VH gene mutation and deletion. These data show that most BCP-ALLs may represent the neoplastic transformation of BCPs destined to die in the bone marrow. 相似文献
97.
Shengfang Jin Jiang Chen Lizao Chen Gavin Histen Zhizhong Lin Stefan Gross Jeffrey Hixon Yue Chen Charles Kung Yiwei Chen Yufei Fu Yuxuan Lu Hui Lin Xiujun Cai Hua Yang Rob A. Cairns Marion Dorsch Shinsan M. Su Scott Biller Tak W. Mak Yong Cang 《Proceedings of the National Academy of Sciences of the United States of America》2015,112(29):9088-9093
Mitochondrial aldehyde dehydrogenase 2 (ALDH2) in the liver removes toxic aldehydes including acetaldehyde, an intermediate of ethanol metabolism. Nearly 40% of East Asians inherit an inactive ALDH2*2 variant, which has a lysine-for-glutamate substitution at position 487 (E487K), and show a characteristic alcohol flush reaction after drinking and a higher risk for gastrointestinal cancers. Here we report the characterization of knockin mice in which the ALDH2(E487K) mutation is inserted into the endogenous murine Aldh2 locus. These mutants recapitulate essentially all human phenotypes including impaired clearance of acetaldehyde, increased sensitivity to acute or chronic alcohol-induced toxicity, and reduced ALDH2 expression due to a dominant-negative effect of the mutation. When treated with a chemical carcinogen, these mutants exhibit increased DNA damage response in hepatocytes, pronounced liver injury, and accelerated development of hepatocellular carcinoma (HCC). Importantly, ALDH2 protein levels are also significantly lower in patient HCC than in peritumor or normal liver tissues. Our results reveal that ALDH2 functions as a tumor suppressor by maintaining genomic stability in the liver, and the common human ALDH2 variant would present a significant risk factor for hepatocarcinogenesis. Our study suggests that the ALDH2*2 allele–alcohol interaction may be an even greater human public health hazard than previously appreciated.Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is essential for alcohol detoxification. It is the second enzyme in the major oxidative pathway of alcohol metabolism, removing acetaldehyde (ACE), a toxic intermediate product from ethanol metabolism (1). More than 500 million people worldwide, mostly in East Asia, have a G-to-A point mutation in their ALDH2 gene (2, 3). This mutation results in a glutamic acid-to-lysine substitution at residue 487 (E487K) of the human ALDH2 protein (designated ALDH2*2). ALDH2*2 has significantly reduced ability to metabolize ACE (4, 5). Importantly, its activity is partially dominant-negative over that of the wild-type ALDH2*1, due to the structural alterations introduced by the mutation to the ALDH2 homotetramer complex (6). As a result, individuals with a heterozygous ALDH2*2/2*1 genotype have less than half the wild-type activity, and ALDH2*2/2*2 homozygotes have very low residual activity (7). Accumulated ACE can cause an alcohol flush reaction, commonly found in Asians with this variant after alcohol consumption (also called “Asian glow”).ACE binds to cellular proteins and DNA, leading to DNA damage and organ injury (8). Specifically, endogenous aldehydes are detrimental to hematopoietic stem cells that are defective in Fanconi anemia DNA repair (9, 10). As a result, Fanconi anemia patients with the ALDH2*2 allele exhibit accelerated disease progression (11). ALDH2*2 can also increase the risk for gastrointestinal cancers, such as gastric carcinoma (12), esophageal cancer (13), and colon cancer (14). Despite the liver being the major organ of ethanol detoxification, the relationship between ALDH2*2 and the risk for liver cancer remains unclear (15, 16).ALDH2 is highly conserved in humans and mice (17, 18), and several mouse models with modified ALDH2 activities have been developed (19). The closest model to the human ALDH2*2 polymorphism is the Aldh2 knockout (KO) mouse, which expresses no protein or enzymatic activity (20). Although Aldh2 KO mice are useful for investigating the impact of complete lack of ALDH2 activity (21), they fail to faithfully reproduce the structural and biochemical properties of ALDH2*2 in human physiology and pathology (21–23). In particular, ALDH2*2 is expressed with reduced but not loss of enzymatic activity and increased protein turnover (24).To provide better mechanistic links between the ALDH2(E487K) mutation and human disease, we generated an ALDH2*2 knockin (KI) mouse. We observed impaired clearance of ACE from hepatocytes in these mutants after acute or chronic alcohol challenges. The ALDH2(E487K) mutation reduced total liver ALDH2 protein levels via a dominant-negative effect on protein stability, as has been documented for human tissues (24, 25). We also revealed a surprising role for ALDH2 as a liver tumor suppressor, raising the concern that this common human polymorphism may expose over 500 million carriers to greater risk of liver cancer. 相似文献
98.
99.
CML patients in blast crisis have breakpoints localized to a specific region of the BCR 总被引:1,自引:0,他引:1
Schaefer-Rego K; Dudek H; Popenoe D; Arlin Z; Mears JG; Bank A; Leibowitz D 《Blood》1987,70(2):448-455
Chronic myelogenous leukemia (CML) is associated with the Philadelphia (Ph) chromosome, which results from a reciprocal translocation between chromosomes 9 and 22. This activates the abl oncogene by moving it from chromosome 9 and combining it with sequence located on chromosome 22. The new fusion gene, with chromosome 22 sequence at its 5' end and chromosome 9-abl sequence at its 3' end, generates a new messenger RNA (mRNA) and protein that are implicated in the pathogenesis of CML. The breakpoint near the c-abl locus on chromosome 9 can occur within a large area. In contrast, the breakpoints on chromosome 22 are concentrated within a 6 kilobase (kb) region termed the breakpoint cluster region (bcr). This study was designed to determine whether chronic-phase and blast crisis patients had identifiable differences in the structure of their Ph chromosomes. Restriction mapping of the chromosome 22 translocation breakpoints performed for 26 patients showed that the breakpoints of eight of the nine patients in blast crisis were in the 3' portion of the bcr, whereas the breakpoints in the 17 patients in the chronic phase were clustered in the 5' portion of the bcr. This suggests a strong correlation between a 3' bcr breakpoint and blast crisis in CML. 相似文献
100.
Drug-induced thrombocytopenia is associated with increased binding of IgG to platelets both in vivo and in vitro 总被引:3,自引:0,他引:3
Kelton JG; Meltzer D; Moore J; Giles AR; Wilson WE; Barr R; Hirsh J; Neame PB; Powers PJ; Walker I; Bianchi F; Carter CJ 《Blood》1981,58(3):524-529
Thrombocytopenia is a common serious adverse effect of drug treatment. A variety of in vitro diagnostic techniques to confirm the diagnosis are available, but the majority lack sufficient sensitivity to detect all cases of drug-induced thrombocytopenia. We studied 19 patients with suspected drug-induced thrombocytopenia and demonstrated that platelet- associated IgG (PAIgG) was elevated in all at the time of thrombocytopenia, and PAIgG returned to normal levels as the thrombocytopenia resolved. In the majority of patients, the platelet count rapidly returned to normal after the drug was discontinued; however, in six patients, the thrombocytopenia persisted well beyond the period of time that the offending drug would be expected to be cleared from the blood. In 13 patients, serum obtained after recovery was used to identify the drug responsible for the thrombocytopenia in an in vitro assay. In all cases, the addition of the drug historically associated with the thrombocytopenic episode was associated with an increased binding of IgG to control platelets. For uncertain reasons, the concentration of drug required to increase the in vitro binding of IgG to test platelets was often more than the concentration usually achieved in vivo. Wider application of these techniques may provide better understanding of the clinical characteristics and mechanisms responsible for drug-induce thrombocytopenia. 相似文献