To test or not to test: an ethical conflict with presymptomatic testing of individuals at 25% risk for Huntington's disorder

The first presymptomatic test for Huntington's disease was developed in the 1980s. With the detection of the gene causing the disorder in 1993, it became possible to do direct mutation tests with almost 100% sensitivity and specificity. The author discusses some of the ethical issues that arise when an adult child at 25% risk for the disease wishes to have the test, but the parent(s) at 50% risk refuses to have one. If the child tests positive, the genetic status of the parent will also be disclosed. No matter what course of action is chosen in this situation, the ethically legitimate interests of either child or parent might be violated. The author examines different alternatives and suggests a solution that might be acceptable to all parties.     

Evidence for interference of vitamin D with PTH/PTHrP receptor expression in opossum kidney cells

 Vitamin D counters the phosphaturic action of parathyroid hormone (PTH) in rats in vivo. The present study was undertaken to examine this interaction using monolayers of Opossum kidney (OK) cells. ³²P uptake, cAMP generation, PTH/PTHrP receptor mRNA expression and intracellular Ca²⁺ [Ca²⁺]_i were measured in (1) control cells, (2) cells exposed to PTH, (3) cells pretreated with 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], and (4) 1,25(OH)₂D₃-pretreated cells exposed to PTH. ³²P uptakes were in (1) 5.00±0.20 (mean ±SE), in (2) 2.30±0.14 (P<0.001 versus group 1), in (3) 4.80±0.24 (P NS versus group 1) and in (4) 3.70±0.20 (P<0.001 versus group 2) nmol P_i/(mg·prot 10 mm). cAMP levels were in (1) 10±3, in (2) 210±8, in (3) 12±4, and in (4) 122±12 pmol cAMP/mg protein (P<0.001 versus group 2). PTH/PTHrP receptor mRNA expression was in relative units: (1) 100±0, (2) 99.5±6.2, (3) 68.7±2.6 (P<0.001 versus group 1), and (4) 34.8±3.3 (P<0.001 versus group 1). In groups 2 and 4 PTH induced equal transient increments in [Ca²⁺]_i. These experiments demonstrate that the effect of vitamin D on phosphate transport is associated with a commensurate diminution in PTH/PTHrP receptor gene expression and PTH-induced cAMP formation but not with Ca²⁺ transients. Vitamin D per se does not affect ³²P uptake or cAMP generation while it slightly decreased PTH/PTHrP receptor gene expression. These observations demonstrate that: (1) 1.25(OH)₂D₃ directly antagonizes the effects of PTH on ³²P uptake in OK cells, (2) this effect is mediated via inhibition of PTH-induced activation of AC/cAMP system, (3) the diminution in PTH-induced cAMP formation may stem at least in part from a decrease in the expression of PTH/PTHrP receptor mRNA. Received: 2 December 1997 / Received after revision: 19 January 1998 / Accepted: 28 January 1998     

Mutation analysis in 16 patients with mtDNA depletion

Sixteen unrelated Southern European patients with the mitochondrial depletion syndrome (MDS) were analyzed for mutations in the TK2 and DGUOK genes. Three novel mutations were identified in TK2 (R183G, R254X, and 142insG). When we analyzed additional genes involved in the dNTPs pool, such as SLC25A19 (DNC) and NT5M (d-NT2), we did not detect mutations. The current study suggest that scanning the TK2, DGUOK, SLC25A19, and NT5M genes is likely to help about 10% of MDS families in terms of genetic counseling. Also, our findings indicate that genotype-phenotype correlations are not straightforward in MDS.     

Cell-bound IgE and increased expression of Fc epsilon-receptors on dendritic cells in cutaneous infiltrates of mycosis fungoides.

Skin biopsies of 31 non-atopic patients, 20 with mycosis fungoides, six with psoriasis and five with contact dermatitis, and of five non-atopic healthy controls were compared for the presence of cell-bound IgE and vacant IgE binding sites. IgE+ cells were demonstrated in the cutaneous infiltrate of nine (45%) patients with mycosis fungoides, two (33%) with psoriasis and one (20%) with contact dermatitis. Following pre-incubation of skin sections with IgE myeloma protein to saturate vacant IgE-binding sites, 14 out of 16 patients (88%) with stage I mycosis fungoides, five (83%) patients with psoriasis and one (20%) with contact dermatitis showed an increase in the number of IgE+ cells. While cell-bound IgE was positively related to serum IgE levels the expression of IgE-binding sites was not. All IgE+ cells were HLA-DR+ dendritic cells identified as either macrophages (CD68+, CD14+) or Langerhans cells (CD1+). Skin biopsies of non-atopic healthy controls or clinically uninvolved skin in mycosis fungoides had neither any IgE+ cells nor any vacant binding sites. Inhibition studies with IgG1, IgG4 and IgE myeloma proteins as well as with several enzymatic fragments of IgE demonstrated that IgE interacted with Fc epsilon-receptors through isotype-specific structures on the Fc epsilon-fragment. Four anti-CD23 monoclonal antibodies, however, were unable to stain vacant Fc epsilon-receptors nor could they block IgE-binding. We hypothesize that locally-secreted lymphokines, like IL-4 or interferon-gamma, induce Fc epsilon-receptors on dendritic cells in the cutaneous infiltrate and that these receptors become occupied in parallel with elevated serum IgE levels.     

The response of heat shock proteins 25 and 72 to ischaemia in different kidney zones

 Induction of heat shock proteins (HSPs) following cell injury contributes to the protection of vital cell functions. It was, therefore, of interest to study the effects of transient renal ischaemia on the abundance and distribution of two HSPs, HSP25 and HSP72, in renal tissue using Western-blot techniques. Analyses were performed on the supernatant (HSP25, HSP72) and pellet (HSP25) of homogenates obtained from cortex (CX) and outer (OM) and inner (IM) medulla of the rat kidney immediately after 60 min of ischaemia followed by varying periods of reperfusion. Ischaemia of the left kidney caused HSP25 contents to decrease in CX, OM and IM by 73, 89 and 54% respectively, compared with the corresponding zones of the contralateral control kidney. This initial decrease in supernatant HSP25 was accompanied by an increased abundance of HSP25 in the pellet. Following reperfusion, HSP25 contents in the supernatant gradually increased in CX and OM, reaching, after 24 h, values that were 5.4- and 2.5-fold higher, respectively, than those in the control kidneys. After 7 or 14 days of reperfusion, HSP25 contents had not completely normalised in CX, but had reached control levels in OM. In IM, the HSP25 content remained below control throughout the entire reperfusion period. HSP72 (supernatant) was below the detection limit in the CX of the control kidney. Similar to the level of HSP25, that of HSP72 was also markedly lower in OM and IM immediately after ischaemia. The intrarenal distribution of HSP72 and the sequence of zonal changes in HSP72 contents were similar to those observed for HSP25. These results are compatible with the view that, during ischaemia and the initial reperfusion period, HSP25 migrates from the cytoplasmic compartment (supernatant) into the nucleus and/or associates with cytoskeletal structures. The observation that both HSP25 and HSP72 are transiently induced in CX and OM, but not in IM, may be explained by the fact that, while all kidney cells are exposed to ischaemic stress, only inner medullary cells experience a major postischaemic attenuation of osmotic stress. Received: 11 February 1997 / Received after revision and accepted: 26 March 1997     

Direct infant UV light exposure is associated with eczema and immune development

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社区呼吸康复治疗在慢性呼吸系统 疾病患者干预管理中的应用*

摘 要： 目的：探究中老年人颈动脉斑块与血清25羟维生素D （25-OH-D） 的相关性。 方法：选取2019年1月—2020 年 12 月自愿参与该研究的上海市浦东新区北蔡社区常住居民 412 人为研究对象,测定及记录其一般临床资料及血清 25-OH-D 等实验室检测结果。依据血管 B 超结果将研究对象分为有斑块组 268 人和无斑块组 144 人,比较两组人群血清 25-OH-D水平差异,用Pearson相关性分析各变量的关系,采用logistic回归分析颈动脉斑块形成的危险因素。结果：有斑块 组血清 25-OH-D 为 （45.18±18.71） nmol/L,无斑块组为 （56.12±19.54） nmol/L,两组差异有统计学意义 （χ2=5.573,P＜ 0.05）。相关性分析显示颈动脉斑块与收缩压、HbA1c、年龄呈正相关 （r值分别为0.388、0.119和0.128,P值均＜0.05）;与 血清 25-OH-D 呈负相关 （r=-0.365,P＜0.01）。血清 25-OH-D 是颈动脉斑块形成的独立相关因素 （OR=0.973,95%CI： 0.960,0.985,P＜0.05）。结论：低水平血清25-OH-D是颈动脉斑块形成的独立危险因素。     

Relationship between Serum 25(OH)D and Depression: Causal Evidence from a Bi-Directional Mendelian Randomization Study

The relationship between depression and vitamin D deficiency is complex, with evidence mostly from studies affected by confounding and reverse causality. We examined the causality and direction of the relationship between 25-hydroxyvitamin D (25(OH)D) and depression in bi-directional Mendelian randomization (MR) analyses using information from up to 307,618 white British participants from the UK Biobank and summary results from the SUNLIGHT (n = 79,366) and Psychiatric Genomics consortia (PGC 113,154 cases and 218,523 controls). In observational analysis, the odds of depression decreased with higher 25(OH)D concentrations (adjusted odds ratio (OR) per 50% increase 0.95, 95%CI 0.94–0.96). In MR inverse variance weighted (IVW) using the UK Biobank, there was no association between genetically determined serum 25(OH)D and depression (OR per 50% higher 0.97, 95%CI 0.90–1.05) with consistent null association across all MR approaches and in data from PGC consortium. In contrast, genetic liability to depression was associated with lower 25(OH)D concentrations (MR IVW −3.26%, −4.94%–−1.55%), with the estimates remaining generally consistent after meta-analysing with the consortia. In conclusion, we found genetic evidence for a causal effect of depression on lower 25(OH)D concentrations, however we could not confirm a beneficial effect of nutritional vitamin D status on depression risk.     

A new interstitial deletion of chromosome No. 4 del(4) (q22::q25)

A female child is described with multiple anomalies including epicanthus, frontal bossing, short sternum, polydactyly, cleft of the larynx, renal cysts, and unusual dermatoglyphics. She died aged 3 months and was found to have a unique de novo deletion of chromosome No. 4 (q22-q25). This case is compared with other long arm deletions of 4q and reference made to assignment of genetic markers to chromosome No. 4.     

不同肝病患者外周血CD25+细胞检测的临床意义

目的 探讨外周血ＣＤ２５＋细胞含量与肝病患者病情转化及预后的关系。方法 采用流式细胞术对１５５例肝病患者及５０名正常人外周血ＣＤ２５＋细胞进行检测,并对６８例治疗好转患者进行治疗前后比较。结果 各种肝病患者外周血ＣＤ２５＋细胞含量明显低于正常对照组（均Ｐ〈０．０１）,其下降程度依次为肝癌患者〉肝炎后肝硬化患者〉慢性活动性肝炎和慢性迁延性肝炎患者。６８例肝病患者治疗后ＣＤ２５＋细胞含量较治疗前明显升