Combined Treatment of Invasive Giant Prolactinomas

The management of invasive giant prolactinomas (IGP) has been an area of some controversy. The relative roles of transsphenoidal surgery, craniotomy, radiation therapy and dopamine agonist based medical therapy are gradually becoming clarified. We report the results of management of 30 patients with IGP. Surgery was the initial therapy in 18 patients and was nearly always followed by adjunctive treatment with radiotherapy and/or bromocriptine. A second group of 12 patients had initial therapy with bromocriptine; 6 had subsequent radiotherapy and only 1 had transsphenoidal surgery. Outcomes with regard to relief of mass effect, visual improvement, pituitary function and complications of therapy were superior in the bromocriptine treated patients. Report of 30 cases     

高血压病伴代谢综合征患者463例的干预治疗研究

目的　分析高血压病伴代谢综合征人群新发糖尿病的预测因素,同时评价较理想的降压药物以降低危险因素,防止糖尿病发生。方法　用随机平行对照临床试验,选轻、中度高血压病患者符合下列 3项中 2项者进入研究: (1)腰围及(或)体质脂数(BMI)异常; (2)甘油三酯(TG)及(或 )低高密度脂蛋白胆固酯(HDL C)升高; (3)糖耐量异常 (IGT)。将患者分成三个干预治疗组: (1)吲哒帕胺+福辛普利组 (第 1组,n=151); (2)阿替洛尔 +尼群地平组 (第 2组,n=160); (3)阿替洛尔+尼群地平+二甲双胍组(第 3组,n=152)。每月随访 1次,按血压水平调整剂量。每 6个月测定空腹血糖及服 75g葡萄糖 2h后血糖,发现异常者定为新发糖尿病而终止试验。在最后随访时重复测定糖耐量试验(OGTT)、胰岛素释放试验(InRT)、血脂、体重及腰围。结果　(1)在三组降压幅度相似(P>0 05)的基础上,新发糖尿病共 23例,三组分别为 10例, 8例, 5例。虽然加服二甲双胍组比不加组新发人数较少但差异未达统计学意义; (2)从三组危险因素构成比看, 第 2、3组,TG升高者在治疗后,分别下降 14 7%及 9 3% (P<0 05),向心性肥胖分别减少 16 7%及 15 9% (P<0 05 ),IGT分别减少 6 6%及 29 6% (P<0 05),而第 1组服药后均无明显变化; (3)平均随访 1年 5个月后基础状态危险因素 (     

Dual role of orphan nuclear receptor pregnane X receptor in bilirubin detoxification in mice

The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are implicated in xenobiotic and endobiotic detoxification, including the clearance of toxic bilirubin. Previous studies have suggested both overlapping and preferential regulation of target genes by these receptors, but the mechanism of cross-talk remains elusive. Here we reveal a dual role of PXR in bilirubin detoxification in that both the loss and activation of PXR led to protection from hyperbilirubinemia induced by bilirubin infusion or hemolysis. The increased bilirubin clearance in PXR-null mice was associated with selective upregulation of detoxifying enzymes and transporters, and the pattern of regulation is remarkably similar to that of transgenic mice expressing the activated CAR. Interestingly, the increased bilirubin clearance and associated gene regulation were absent in the CAR-null or double-knockout mice. In cell cultures, ligand-free PXR specifically suppressed the ability of CAR to induce the multidrug resistance associated protein 2 (MRP2), a bilirubin-detoxifying transporter. This suppression was, at least in part, the result of the disruption of ligand-independent recruitment of coactivator by CAR. In conclusion, PXR plays both positive and negative roles in regulating bilirubin homeostasis, and this provides a novel mechanism that may govern receptor cross-talk and the hierarchy of xenobiotic and endobiotic regulation. PXR is a potential therapeutic target for clinical treatment of jaundice. (HEPATOLOGY 2005;41:497-505.).     

A study of HLA-G1 protection of porcine endothelial cells against human NK cell cytotoxicity

Human natural killer (NK) cells, which can directly lyse porcine endothelial cells, play an important role in xenotransplantation. HLA-G is a nonclassical major histocompatibility complex (MHC) class I molecules that has been implicated in protecting susceptible target cells from lysis by NK cells. The objective was to study the effect of protecting porcine endothelial cells transfected with HLA-G1 from human NK cell lysis. METHODS: The recombinant expression vector pcDNA3-HLA-G1 was transfected into primary cultured porcine aortic endothelial cells (PAECs) by lipofection. Surface expression of HLA-G1 in transected PAECs was confirmed by an immunofluoresence technique. Peripheral blood mononuclear cells (PBMC) and NK cell line (NK92) were used as NK effects cells with pcDNA3-HLA-G1-transfected PAECs as targets in a MTT method using pcDNA3 transfection as a negative control. RESULTS: Expression of HLA-G1 on PAECs conferred significant protection against NK-mediated lysis. The rate of NK92 cytotoxicity was reduced to 41.5% +/- 14.0% from 75.3% +/- 10.5% in the control group (P < .01). Similarly the rate of the PBMC cytotoxicity among different donors (n = 7) was reduced to 45.4% +/- 12.1% in contrast to 74.6% +/- 11.2% in the control group (P < .05). CONCLUSIONS: HLA-G1 molecules can directly protect xenogeneic PAECs against attack by human NK cells. These results indicate that the expression of HLA-G1 on the porcine cell surface may provide a new approach to overcome NK-mediated immunity to xenografts.     

GJB2 gene mutations in newborns with non-syndromic hearing impairment in Northern China

Mutations in GJB2 account for the majority of recessive forms of prelingual hearing loss. However, in most previous studies it was not possible to distinguish between congenital (present at birth) and non-congenital prelingual hearing loss. In the present study, the frequency of GJB2 alleles in 20 newborns with bilateral severe-to-profound non-syndromic hearing impairment (NSHI) who were found at birth through newborn hearing screening and clinical examination is reported. PCR was used to amplify the coding region of GJB2 gene followed by sequencing analyses. Fifty volunteers with normal hearing were included as controls. Results showed that three cases were 235delC/235delC homozygotes; one was 235delC/605ins46 compound heterozygotes, 605ins46 mutation was a novel mutation reported in the Chinese population; another was 235delC/299-300delAT compound heterozygotes. 25% (5/20) of the deafness in newborns studied was caused by GJB2 gene mutations. The frequency of 235delC allele carrier in patients and in control group was 22.5% and 1%, respectively. One case was identified as being a 235delC heterozygote without other mutations detected. Besides, multiple polymorphisms such as V27I, V37I, E114G, T123N were also detected. In conclusion, GJB2 analysis is an important test that identifies a major cause of newborns with bilateral severe-to-profound NSHI screened by universal newborn hearing screening in Northern China. The most common pathologic mutation of GJB2 in studied cases was 235delC. Molecular analysis and genetic counseling will be extremely important for congenital deafness present at birth.     

Postweaning exposure to aflatoxin results in impaired child growth: a longitudinal study in Benin, West Africa

Aflatoxins are dietary contaminants that are hepatocarcinogenic and immunotoxic and cause growth retardation in animals, but there is little evidence concerning the latter two parameters in exposed human populations. Aflatoxin exposure of West African children is known to be high, so we conducted a longitudinal study over an 8-month period in Benin to assess the effects of exposure on growth. Two hundred children 16-37 months of age were recruited from four villages, two with high and two with low aflatoxin exposure (50 children per village). Serum aflatoxin-albumin (AF-alb) adducts, anthropometric parameters, information on food consumption, and various demographic data were measured at recruitment (February) and at two subsequent time points (June and October). Plasma levels of vitamin A and zinc were also measured. AF-alb adducts increased markedly between February and October in three of the four villages, with the largest increases in the villages with higher exposures. Children who were fully weaned at recruitment had higher AF-alb than did those still partially breast-fed (p < 0.0001); the major weaning food was a maize-based porridge. There was no association between AF-alb and micronutrient levels, suggesting that aflatoxin exposure was not accompanied by a general nutritional deficiency. There was, however, a strong negative correlation (p < 0.0001) between AF-alb and height increase over the 8-month follow-up after adjustment for age, sex, height at recruitment, socioeconomic status, village, and weaning status; the highest quartile of AF-alb was associated with a mean 1.7 cm reduction in growth over 8 months compared with the lowest quartile. This study emphasizes the association between aflatoxin and stunting, although the underlying mechanisms remain unclear. Aflatoxin exposure during the weaning period may be critical in terms of adverse health effects in West African children, and intervention measures to reduce exposure merit investigation.     

Induction of anti-leukemic cytotoxic T lymphocytes by fusion of patient-derived dendritic cells with autologous myeloblasts

Presentation of AML antigens by dendritic cells (DC) could potentially induce a T cell-mediated anti-leukemic immune response. In the present study, we generated DC from adherent (AD-DC) and non-adherent (NAD-DC) myeloblasts obtained from bone marrows of AML patients. Both cell populations displayed morphological, phenotypic and functional properties of DC. The functions of NAD-DC were compared to AD-DC that had been fused with autologous AML blasts (FC/AML). The FC/AML induced greater T cell proliferation and CTL activity against autologous AML blasts (9/10 cases) as compared to NAD-DC. FC/AML may thus represent a promising strategy for DC-based immunotherapy of patients with AML.