The 11q;22q translocation: A European collaborative analysis of 43 cases

Summary Translocation between the long arms of chromosomes 11 and 22 is usually detected in offspring with an unbalanced karyotype following a 3:1 disjunction resulting in partial trisomy. Since by the end of 1976 it was suspected that this translocation might be more frequent than one would deduce from published reports, it was decided to call for a collaborative effort in Europe to collect unpublished cases. In response, 42 cases were collected in Europe, and one case from New Zealand was added. The following countries were represented with the number of cases indicated in parentheses: Czechoslovakia (2), Denmark (4), Finland (3), France (6), Germany (1), Italy (5), The Netherlands (9), Sweden (6), United Kingdom (4), Yugoslavia (2). The wide geographical distribution indicates a multifocal origin of the translocation. Among the unpublished cases, 31 were ascertained as unbalanced carriers [47,XX or XY,+der(22),t(11;22)] and 12 as balanced balanced carriers [46,XX and XY,t(11;22)]. Among the published cases, 10 were ascertained in unbalanced and 3 in balanced carriers. The breakpoints of the translocations indicated by the contributors varied, the most frequently reported being 11q23;22q11 (25 cases), followed by q25;q13 (10 cases). While the first one seems more likely, it was not possible to decide whether the breakpoints were the same in all cases.All 32 probands with unbalanced karyotypes had inherited the translocation, 31 from the mother and only 1 from the father. This ratio became 43:1 when the published cases were added. A segregation analysis revealed that in families ascertained through probands with unbalanced karyotypes there was a ratio of carriers to normal (all karyotyped) 54:55, not a significant difference. The formal maximum (minimum) recurrence risk for this unbalanced translocation was calculated to be 5.6% (2.7%). When the ascertainment was through a balanced proband, the maximum risk was 2.7%. The risk was calculated as 5.7% for female and 4.3% for male carriers. The mean family size was 1.67 for the offspring of female carriers and 0.78 for the offspring of male carriers. This significant difference suggests that heterozygosity for the translocation reduces fertility in males. Indeed, several of the probands with balanced karyotypes were ascertained because of sub- or infertility. Only 2 de novo translocations were found among the 59 probands, and both, were among the 12 cases ascertained as balanced carriers. The source, quality, and quantity of the clinical data for the subjects with unbalanced karyotypes were variable, and no definite conclusions were possible about phenotypes. The following signs were recorded in 10 or more of the 45 cases: low birth weight, delayed psychomotor development, hypotonia, microcephaly, craniofacial asymmetry, malformed ears with pits and tags, cleft palate, micro-/retrognathia, large beaked nose, strabismus, congenital heart disease, cryptorchidism, and congenital dislocation of the hip joints. Many signs were similar to those considered typical of trisomy 11q, and the phenotype coincided almost completely with the presumptive phenotype of complete trisomy 22. No cases with coloboma was recorded, while other signs of the cat-eye syndrome were found in several probands. This might indicate that individuals with the cat-eye syndrome and carriers of the unbalanced 11/22 translocation have the same segment of 22 in triplicate plus or minus another chromosome segment.     

Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans

To survive elevated temperatures, ectotherms adjust the fluidity of membranes by fine-tuning lipid desaturation levels in a process previously described to be cell autonomous. We have discovered that, in Caenorhabditis elegans, neuronal heat shock factor 1 (HSF-1), the conserved master regulator of the heat shock response (HSR), causes extensive fat remodeling in peripheral tissues. These changes include a decrease in fat desaturase and acid lipase expression in the intestine and a global shift in the saturation levels of plasma membrane’s phospholipids. The observed remodeling of plasma membrane is in line with ectothermic adaptive responses and gives worms a cumulative advantage to warm temperatures. We have determined that at least 6 TAX-2/TAX-4 cyclic guanosine monophosphate (cGMP) gated channel expressing sensory neurons, and transforming growth factor ß (TGF-β)/bone morphogenetic protein (BMP) are required for signaling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodeling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell nonautonomously coordinate membrane saturation and composition across tissues in a multicellular animal.

In response to heat, ectotherms exhibit an adaptive response characterized by changes in membrane fluidity. This study in the nematode Caenorhabditis elegans shows that neuronal HSF-1 is critical for this remodeling, suggesting a neuronal thermostat-based mechanism that can non-cell-autonomously coordinate the animal’s response to heat.     

肝病患者肝组织IL-18结合蛋白的表达和分析

目的:探讨肝病患者肝脏组织白细胞介素18结合蛋白(interleukin-18 binding protein,IL-18BP)的表达水平及临床意义.方法:应用免疫组织化学技术检测41例原发性肝癌、9例慢性乙型肝炎、11例肝硬化、和5例正常肝组织中IL-18BP的表达情况,同时检测患者外周血IL-18BP的含量.结果:原发性肝癌的癌周组织IL-18BP表达量最高,与癌组织、肝硬化组织、慢性肝炎组织和正常肝组织评分值组间比较差异有统计学意义(P＜0.01);表达强度:癌周组织＞肝硬化＞肝癌＞慢性肝炎,正常组织无阳性表达(P＜0.01).IL-18BP在组织中的表达和血清中的含量相一致.结论:肝病患者IL-18BP表达水平随病情加重呈递增趋势.     

Assessment of genetic diversity in cultivars of white clover (Trifolium repens L.) detected by SSR polymorphisms.

White clover (Trifolium repens L.) is an important temperate pasture legume that plays a key role as a companion to grass species, such as perennial ryegrass (Lolium perenne L.). Due to the outbreeding nature of white clover, cultivars are highly heterogeneous. Genetic diversity was assessed using 16 elite cultivars from Europe, North and South America, Australia, and New Zealand. Fifteen simple sequence repeat markers that detect single, codominant polymorphic genetic loci were selected for the study. The genetic relationships among individuals were compared using phenetic clustering, and those among cultivars were compared using nonmetric multidimensional scaling. Intrapopula tion variability exceeded interpopulation variability, with substantial overlap among populations and weak interpopula tion differentiation. No obvious or significant differentiation was observed on the basis of morphology or geographic origin of the cultivars. The number of parental genotypes used to derive each cultivar was not a major determinant of genome-wide genetic diversity. The outcomes of this assessment of genetic variation in elite white clover germplasm pools have important implications for the feasibility of molecular marker-based cultivar discrimination, and will be used to assist the design of linkage disequilibrium mapping strategies for marker-trait association.     

Behavior of 3α- and 7α-hydroxysteroid dehydrogenases on chenodeoxycholate substituted sepharose

Chenodeoxycholate (3α-, 7α-dihydroxy-5β-cholanoate) was linked to Sepharose 4B by an ethylenediamine bridge. When 3α-hydroxysteroid dehydrogenase and 7α-hydroxysteroid dehydrogenase preparations were applied to a column of covalently linked Chenodeoxycholate, both enzymes were retarded at pH 6.7; the 7α-OH oriented enzyme more than the 3α-OH enzyme. Approximately forty-fold purification of 7a-hydroxysteroid dehydrogenase was achieved in one step. Although no significant purification of 3α-hydroxysteroid dehydrogenase occurred, the background value in the fluorometric enzymatic estimation of bile acids by eluted 3α-hydroxysteroid dehydrogenase was markedly reduced. Molecular weight estimation by Sephadex G-200 gave the values of 47,000 for 3α-hydroxysteroid dehydrogenase and 105,000 for 7α-hydroxy-steroid dehydrogenase.     

Rethinking patient involvement in healthcare priority setting

With healthcare systems under pressure from scarcity of resources and ever-increasing demand for services, difficult priority setting choices need to be made. At the same time, increased attention to patient involvement in a wide range of settings has given rise to the idea that those who are eventually affected by priority setting decisions should have a say in those decisions. In this paper, we investigate arguments for the inclusion of patient representatives in priority setting bodies at the policy level. We find that the standard justifications for patient representation, such as to achieve patient-relevant decisions, empowerment of patients, securing legitimacy of decisions, and the analogy with democracy, all fall short of supporting patient representation in this context. We conclude by briefly outlining an alternative proposal for patient participation that involves patient consultants.     

Long-term patterns of agonistic interactions in a captive group of wolves (Canis lupus)

Agonistic interactions were recorded in a captive group of wolves (Canis lupus) for a period of 21 months. Seventy-five per cent of all interactions were accounted for by only 4 or less of a possible 28 pairs during any given period of the study. Several animals were involved in very few agonistic interactions, and in many relationships such interactions were absent. Patterns of agonistic interaction alone did not suggest social relationships or an overall social structure applicable to all group members, although some evidence of a dominance hierarchy was found. Patterns of agonistic interactions were shown to involve several independent dimensions in different relationships. Further details of an underlying social organization are likely to emerge only from long-term studies which examine several dimensions of, and the interrelations between, a wide range of social interactions.     

Structural basis of translation termination,rescue, and recycling in mammalian mitochondria

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