促性腺激素释放多肽(GRP)对体外培养小鼠垂体分泌LH的影响

合成的促性腺激素释放多肽(GRP)及其类似物GRp～NH₂,[Glu^7.9.14Lys^6.10]GRP(6～14),[phe¹⁴]GRP(5～14)和[phe¹⁴]GRP浓度在0.05mmol·L^-1时,具有刺激体外培养的小鼠垂体分泌LH的作用。其活性依此相当对照垂体的115.4,114.2,140,160和179%。小鼠于妊振第7～9天或第1～5天,每只sc[phe¹⁴]GRP1mg·d^-1,或于妊娠第2～4天每只sc[phe¹⁴]GRP(5～14)1mg·d^-1,有40～60%的妊娠动物出现死胎。     

A1, a Bcl-2 family member, prolongs cell survival and permits myeloid differentiation

A1, a bcl-2 family member, has been identified as a hematopoietic- specific, early inducible gene. In this study it is shown that stable transfection of A1 into an interleukin-3 (IL-3)-dependent myeloid precursor cell line, 32D c13, leads to a retardation of IL-3 withdrawal- induced cell death similar to that observed with transfection of bcl-2. However, unlike bcl-2. A1 expression permits the accumulation of differentiated myeloid cells both before and after IL-3 withdrawal. Total cell accumulation, on the other hand, is considerably greater after IL-3 deprivation in the bcl-2 transfectant than in A1-expressing cells. Cells cotransfected with the two genes behave similarly to cells singly transfected with bcl-2, except that viability following IL-3 withdrawal is somewhat further enhanced. These results suggest that these two proteins have distinct roles that may be related to the divergent regulation of their expression during myeloid differentiation.     

High-dose multidrug resistance in primary human hematopoietic progenitor cells transduced with optimized retroviral vectors

Retroviral transfer of the multidrug-resistance 1 (mdr1) cDNA into primary human hematopoietic progenitor cells (HPC) of cancer patients undergoing high-dose chemotherapy has been proposed to protect the bone marrow from the dose-limiting cytotoxicity of cytostatic agents. Preclinical studies performed with vectors derived from the Moloney murine leukemia virus (MoMuLV) or the related Harvey murine sarcoma virus have established that chemoprotection of HPC is feasible. The efficacy of vector-mediated multidrug-resistance under high doses of cytostatic agents, however, remained unclear. We report here that this goal can only be achieved with improved vector design. Novel vectors termed SF-MDR and MP-MDR, which are based on the spleen focus-forming virus or the myeloproliferative sarcoma virus for the enhancer and the murine embryonic stem cell virus for the leader, significantly elevate survival of transduced primary human HPC under moderate doses of colchicine and paclitaxel in vitro when compared with a conventional MoMuLV-based vector. Importantly, SF-MDR and also MP-MDR confer an absolute advantage at high doses of paclitaxel in vitro corresponding to peak plasma levels achieved in patients during chemotherapy. This observation has important consequences for a variety of ongoing and planned gene therapy trials.     

Determinants of disease expression in Australian haemochromatosis patients

Many of the clinical manifestations of haemochromatosis are determined by the hepatic iron concentration which, in turn, may be influenced by environmental and genetic factors. The environmental factors that influence iron stores include age, gender and blood loss (pathological and physiological). There is evidence that genetic factors also influence hepatic iron accumulation, as patients with two copies of the ancestral haplotype accumulate more iron than subjects with one or no copies of the ancestral haplotype. Concordance of iron storage between siblings also suggests genetic factors play an important role in determining disease expression. However, clarification of the exact role of genetic factors awaits the conduct of further studies following the cloning of the haemochromatosis gene.     

Inter- and intrachromosomal sub-telomeric rearrangements on 4q35: implications for facioscapulohumeral muscular dystrophy (FSHD) aetiology and diagnosis

The autosomal dominant myopathy facioscapulohumeral muscular dystrophy (FSHD) is causally related to a short Eco RI fragment detected by probe p13E-11. This remnant fragment is the result of a deletion of an integral number of tandemly arrayed 3.3 kb repeat units (D4Z4) on 4q35. Despite intensive efforts, no transcribed sequences have been identified within this array. Previously, we have shown that these repeats on 4q35 have been exchanged for a similar highly homologous repeat locus on 10q26 in 20% of the population and that a short chromosome 10-like array on 4q35 also results in FSHD. Here, we describe the hybrid structure of some of these repeat arrays, reflecting additional sub-telomeric instability. In three healthy individuals carrying a 4-like repeat on chromosome 10 or vice versa, one repeat array was shown to consist of hybrid clusters of 4-derived and 10-derived repeat units. Moreover, employing pulsed field gel electrophoresis analysis, we identified two unrelated individuals carrying deletions of a chromosomal segment (p13E-11) proximal to the repeat locus. These deletions were not associated with FSHD. In one of these cases, however, an expansion of the deletion into the repeat array was observed in one of his children suffering from FSHD. These data provide additional evidence for instability of this sub-telomeric region and suggests that the length of the repeat, and not its intrinsic properties, is crucial to FSHD. Moreover, they are in agreement with the hypothesis that FSHD is caused by a position effect in which the repeat structure influences the expression of genes nearby. Therefore, the region deleted proximal to the repeat locus in healthy individuals can be instrumental to refine the critical region for FSHD1.      

Compensatory structural and functional adaptation after radical nephrectomy for renal cell carcinoma according to preoperative stage of chronic kidney disease. Choi DK,Jung SB,Park BH,Jeong BC,Seo SI,Jeon SS,Lee HM,Choi HY,Jeon HG.J Urol. 2015 Oct;194(4):910-5. [Epub 2015 Apr 28]. doi: 10.1016/j.juro.2015.04.093.

Purpose

We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage.

P08 Comparing study in self-motivation learning： PBL vs LBL

In order to clarify which teaching form encourages student＇ s self-motivation learning ability better, we did a comparison experiment between problem-based learning （PBL）and lecture-based learning （LBL） in a 3rd year course in basic pharmacology. Of 224 students who participated （124 PBL, 100 LBL） in pharmacology course, the experimental group was divided into 6 teams（20 - 21 students for each team with one tutor）using PBL method with 7 clinical cases discussion while o.ther 100 students held in the same lecture-based format as the traditional LBL course as a control group. In 224 students, 50.4% using PBL method self-directed learning ability had increased compared with 35.3% in LBL teaching mode. The test score indicated that students using LBL teaching method scored overall higher than those using PBL mode, especially at objective items, this result was significant.. iy different（P =0.009）. However, as far as subjective items are concerned, students accepted PBL mode showed their superior advantages over the LBL ones. Similarly, the result was significantly different（ P =0.001 ）. On the whole, PBL method supported by appropriate technology and teachers, has allowed our students to analyze authentic situations as a doctor status and the active learning ability by self-motivation study will be undoubtedly beneficial for their becoming life-long learners and excellent doctors in the future.     

Estimating the risk of gestational diabetes mellitus: a clinical prediction model based on patient characteristics and medical history

Objective  To develop a clinical prediction rule that can help the clinician to identify women at high and low risk for gestational diabetes mellitus (GDM) early in pregnancy in order to improve the efficiency of GDM screening.
Design  We used data from a prospective cohort study to develop the clinical prediction rule.
Setting  The original cohort study was conducted in a university hospital in the Netherlands.
Population  Nine hundred and ninety-five consecutive pregnant women underwent screening for GDM.
Methods  Using multiple logistic regression analysis, we constructed a model to estimate the probability of development of GDM from the medical history and patient characteristics. Receiver operating characteristics analysis and calibration were used to assess the accuracy of the model.
Main outcome measure  The development of a clinical prediction rule for GDM. We also evaluated the potential of the prediction rule to improve the efficiency of GDM screening.
Results  The probability of the development of GDM could be predicted from the ethnicity, family history, history of GDM and body mass index. The model had an area under the receiver operating characteristic curve of 0.77 (95% CI 0.69–0.85) and calibration was good (Hosmer and Lemeshow test statistic, P  = 0.25). If an oral glucose tolerance test was performed in all women with a predicted probability of 2% or more, 43% of all women would be tested and 75% of the women with GDM would be identified.
Conclusions  The use of a clinical prediction model is an accurate method to identify women at increased risk for GDM, and could be used to select women for additional testing for GDM.