Inhibition of dendritic cell maturation by malaria is dose dependent and does not require Plasmodium falciparum erythrocyte membrane protein 1

Red blood cells infected with Plasmodium falciparum (iRBCs) have been shown to modulate maturation of human monocyte-derived dendritic cells (DCs), interfering with their ability to activate T cells. Interaction between Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and CD36 expressed by DCs is the proposed mechanism, but we show here that DC modulation does not require CD36 binding, PfEMP1, or contact between DCs and infected RBCs and depends on the iRBC dose. iRBCs expressing a PfEMP1 variant that binds chondroitin sulfate A (CSA) but not CD36 were phagocytosed, inhibited lipopolysaccharide (LPS)-induced phenotypic maturation and cytokine secretion, and abrogated the ability of DCs to stimulate allogeneic T-cell proliferation. CD36- and CSA-binding iRBCs showed comparable inhibition. P. falciparum lines rendered deficient in PfEMP1 expression by targeted gene knockout or knockdown also inhibited LPS-induced phenotypic maturation, and separation of DCs and iRBCs in transwells showed that inhibition was not contact dependent. Inhibition was observed at an iRBC:DC ratio of 100:1 but not at a ratio of 10:1. High doses of iRBCs were associated with apoptosis of DCs, which was not activation induced. Lower doses of iRBCs stimulated DC maturation sufficient to activate autologous T-cell proliferation. In conclusion, modulation of DC maturation by P. falciparum is dose dependent and does not require interaction between PfEMP1 and CD36. Inhibition and apoptosis of DCs by high-dose iRBCs may or may not be physiological. However, our observation that low-dose iRBCs initiate functional DC maturation warrants reevaluation and further investigation of DC interactions with blood-stage P. falciparum.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Cryopreservation of all prezygotes in patients at risk of severe hyperstimulation does not eliminate the syndrome, but the chances of pregnancy are excellent with subsequent frozen-thaw transfers

In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic gonadotrophin administration and 25 or more follicles of intermediate or large size) underwent aspiration of all follicles and cryopreservation of all fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2 weeks post- retrieval. Subsequent transfer of cryopreserved-thawed embryos was performed in programmed cycles using exogenous oestrogen and progesterone for endometrial preparation. Two patients (13%) developed OHSS necessitating hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%) developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office setting, with dramatic improvement of the condition. Subsequent transfer of cryopreserved- thawed embryos yielded a clinical pregnancy rate of 58% per transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient respectively. By eliminating pregnancy potential with cryopreservation of all prezygotes and examining the pregnancy potential with subsequent cryopreserved-thawed transfers, it is concluded that OHSS is reduced, but not eliminated for patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a programmed cycle with exogenous steroids yields an excellent pregnancy rate.      

Palmar Type of Median Artery as a Source of Superficial Palmar Arch: A Cadaveric Study with Its Clinical Significance

The superficial palmar arch (SPA) and its contributing arteries are highly variable. The palmar type of median artery (PMA) can be involved in the formation of the SPA by replacing the superficial palmar branch of the radial artery (RA) or the ulnar artery (UA). The present study was undertaken to investigate the presence of the PMA and its contribution in the formation of SPA in 42 cadavers (84 upper limbs) of Indian origin. When there was a PMA, its outer diameter was measured in the carpal tunnel. The PMA was found in 13 upper limbs (15.4%), and of these ten incidences (11.9%), the PMA took part in the formation of SPA, and in three instances (3.5%), the PMA did not make up part of the SPA. Out of the ten cases in which the PMA contributed to the formation of SPA, in six cases (7.1%), the PMA anastomosed with the UA; in three cases (3.5%), the PMA anastomosed with both the UA and the RA, and in one incidence (1.1%), the PMA joined the arteria radialis indicis (deep branch of the RA) to complete the SPA. The outer diameters of the median arteries varied between 0.8 and 2.6 mm with the mean value of 1.7 mm. The present study concludes that the median–ulnar type of SPA was the most common type of SPA when the PMA was encountered as a source of superficial arterial arcade of the hand, followed by the radial–median–ulnar type. The vascular patterns found in this study are important to hand surgeons. The present study of PMA origin, course, and its contribution to the SPA will add to the existing knowledge of the vascular anatomy of forearm and hand.     

Carriage of Haemophilus influenzae and Streptococcus pneumoniae in healthy Chinese and Vietnamese children in Hong Kong

Nasopharyngeal carriage of Haemophilus influenzae and Streptococcus pneumoniae was studied in 621 healthy Chinese children and 300 healthy Vietnamese children aged from 2 months to 5 years in Hong Kong. The carriage rate of H, influenzae type b in Vietnamese children was 1.3% (CI 0.04-2.63%); it was zero in Chinese. The carriage rate of non-typable H. influenzae was 5.8% (CI 1.4-7.6%) in Chinese and 65.4% (CI 58.9-69.8%) in Vietnamese. The carriage rates of S. pneumoniae were 10.8% (CI 8.3-13.2%) and 55.7% (CI 50.1-61.3%) in Chinese and Vietnamese children, respectively. Univariate and multivariate logistic regression analyses were performed to search for factors associated with differences in carriage rates of both H. influenzae and S. pneumoniae between Chinese and Vietnamese children. Although older age, smaller living area and parental smoking were associated with higher carriage rates, these could not explain the remarkably low carriage rates of both bacteria in Chinese children.     

Genetic Engineering and Medical Ethics

In the introduction I express the need of introducing the point of view of Ethics when we are dealing with problems of science, technology, and especially medicine. In the first part of my presentation I deal with the problem of the value of human life, coming to the conclusion that human life might not be completely absolute, but is extremely important and “ceteris paribus” should be respected, and the problem of when it starts. Some of the main arguments are discussed. In this connection the question of abortion is briefly discussed. In the second part I deal with some problems related to human reproduction. Most people will be willing to support programmes for treating individuals with genetic disease; but at the same time the dangers of increasing depersonalization of the reproductive process are pointed out. In the third part I take up the problem of In Vitro Fertilisation. IVF has certainly brought benefits to some couples suffering from infertility, but at the same time it has raised quite a few human and moral problems. Is it permissible to fertilise an egg with a donor sperm, replacing the embryo in the womb? What about fertilising a donor egg with the husband's sperm? Is it acceptable to store or freeze embryos for future use? Is it moral to implant such an embryo in a woman who has no genetic relationship with the embryo? Is it moral to use surrogate mothers? Is it moral for ‘spare’ embryos to be killed or used as tissue for research? At the end I stress the need of dialogue between life sciences and ethics.     

贴报-P2临床毒理学、药理学和疗效研究

5-Flourouracil（5-FU） is one of well known anti-cancer drugs, but its toxicity in normal lymphocytes remains a major problem in chemotherapy. The eastern traditional drug, Bupleuri radix（BR）, has been used for the treatment of liver diseases and contains series of triterpene saponins.     

子宫肌瘤与性激素及细胞凋亡的关系

1对象和方法 1.1对象随机抽取2001-10/2002-09我科住院行子宫全切术的34例子宫肌瘤患者,其中卵泡期18例,黄体期16例,年龄35~45岁. 术后均经病理证实,在手术前3 mo均未接受过激素治疗,肌瘤大小为3~8 cm3. 自肌瘤瘤体及瘤旁肌层组织各取材1份作配对比较. 瘤体为实验组,肌层为对照组. 鼠抗人ER, PR, PRL-R, Bcl-2 mAb及链霉菌抗生物素蛋白-过氧化物酶(SP)免疫组化试剂盒,均购自福州迈新生物技术开发公司.