Selectivity of excitotoxic mechanisms in Alzheimer's disease

Dysfunction of glutamatergic neurons in Alzheimer's disease may actually participate in some of the neurodegenerative processes via potential excitotoxic mechanisms. Two hypotheses are advanced which describe how a generalized excitotoxic mechanism could interact with unique metabolic properties of specific cell types leading to their selective vulnerability in Alzheimer's disease.     

Lactoferrin gene expression is estrogen responsive in human and rhesus monkey endometrium.

We have previously shown that the estrogen responsiveness of the human lactoferrin gene in a transient transfection system is mediated through an imperfect estrogen response element (ERE) and a steroidogenic factor 1 binding element (SFRE) 26 bp upstream from ERE. Reporter constructs containing SFRE and ERE respond to estrogen stimulation in a dose-dependent manner, whereas mutations at either one of the response elements severely impaired the estrogen responsiveness. In this study, we demonstrated that estrogen receptor (ERalpha) binds to the human lactoferrin gene ERE and forms two complexes in an electrophoresis mobility shift assay (EMSA). These complexes could be supershifted by an antibody to ERalpha. We also showed that in normal cycling women, lactoferrin gene expression in the endometrium increases during the proliferative phase and diminishes during the luteal phase. This in-vivo study thus supported the finding from transient transfection experiments that the human lactoferrin gene expression is elevated in an environment with a high level of estrogen. The estrogen effect on lactoferrin gene expression in the rhesus monkey endometrium was studied by Western blotting and immunohistochemistry. The immunohistochemistry results showed that immunoreactive lactoferrin protein was not detectable in the untreated ovariectomized monkey endometrium, was elevated by estrogen treatment, and was suppressed by sequential, combined estrogen plus progesterone treatment. In conclusion, this study has shown that lactoferrin gene expression is responsive to estrogen in primate endometrium.     

Characterization of SV40 enhancer motifs involved in positive and negative regulation of the constitutive late promoter activity; effect of T-antigen.

By analyzing the late promoter activity of a series of nonreplicative recombinants mutated within the different enhancer motifs of SV40 we identified both positive and negative regulatory elements. In the absence of T-antigen, the motifs Sph and/or octamer, and to a lesser extent the motifs GTI and P, account for the constitutive expression of the late promoter. The motif GTII overlaps elements that negatively regulate the expression of the late promoter. These results indicate that the late promoter is down-regulated not only at the level of the GC motifs but also at the enhancer level. Moreover, we showed that T-antigen interacts with both positive and negative regulatory elements.     

The polymorphism of HLA-DR3 in South African populations

The polymorphism of HLA-DR3 was investigated in families and unrelated individuals of three population groups: South African (SA) Negroes, Cape Coloureds and SA Caucasoids. Serological and restriction fragment length polymorphism (RFLP) analysis indicated that DR3 could be subdivided into DRw17 (previously DR3.1) and DRw18 (previously DR3.2). In contrast, the two-dimensional (2-D) gel electrophoresis patterns could not distinguish between the DRB1 gene products of the HLA-DRw17 and DRw18 cells. Two DRB3 variants, correlating with the T-cell defined specificities Dw24 and Dw25 were identified at the genomic and product level. Of ten haplotypes studied with the newly defined HLA-DRw18 specificity, all had the DRB3 RFLP pattern associated with Dw24. HLA-DRw17 was found in all three population groups tested, although in the SA Negroes HLA-DRw18 was the prevalent DR3 subgroup. This subgroup was also present in the Cape Coloureds but was absent in the SA Caucasoid tested. HLA-DRw18 forms part of the most characteristic SA Negro haplotype, Bw42, DQw4, Dw“RSH,” while HLA-DRw17 is part of the classic Caucasoid haplotype, B8, DQw2, Dw3.     

Student's perceptions of a virtual PBL experience.

OBJECTIVE: Our purpose is to present findings regarding student attitudes towards a virtual PBL program used to standardize their pediatric clinical experience. DESCRIPTION: With funding provided by the Fund for the Improvement of Post-Secondary Education, we developed Project LIVE (Learning through Interactive Video Education), a CD-ROM/Web hybrid program that uses digital video cases to conduct "virtual" problem-based learning groups with students doing a clinical rotation in a remote setting. Cases were progressively disclosed by videos of patient/physician encounters on a CD-ROM. Groups of five students and a faculty facilitator collaborated, teaching each other within the discussion section of the program. We conducted a multifaceted evaluation of Project LIVE to study the impact of case modality or distance on student learning and attitudes. We placed students in one of three groups (1) a face-to-face group with a paper case (FFT), (2) a face-to-face group with a video case (FFV), and (3) a virtual group (VG) with the digital video case. We then studied student attitudes about the three teaching formats. Over a six-month period three education specialists, who were not a part of the development team, conducted eight focus groups lasting one hour to assess student attitudes about Project LIVE. No one from the project team was present during these groups, and an independent evaluator analyzed the notes taken by each focus group leader. DISCUSSION: Trends across the groups included the following: (1) Authenticity (video)-Students reported that the authenticity of the case was a critical feature and that, "seeing (videos) made learning more memorable." Virtual and FFV groups reported more confidence in their ability to recognize abnormal findings in their patients. "You can't expect to teach clinical exam skills with a piece of paper." (2) Use of time-Students from all groups believed the cases were a good use of their time and improved their ability to solve clinical problems. They said it gave them an opportunity to "get away from just doing and focus on learning." However, the virtual groups complained of the lack of "a barometer for how much is too much" time. Some students reported spending an average of eight to ten hours per case over the period of a week. (In contrast, face-to-face groups met for three hours.) (3) Modeling clinical reasoning-Students believed the cases were valuable in structuring their knowledge, conceptualizing how to handle difficult situations, distinguishing abnormal from normal physical examination findings, and collaborating with their peers and their mentor to develop critical thinking. "It forced us to be logical" and ". how to think through the process-it mimics the real setting." (4) Technical support-The responsiveness of the Project LIVE staff was essential in assisting students in troubleshooting problems. (5) Distance component-Students preferred to work through the cases in face-to-face groups but agreed that the virtual experience is "good if you are in the middle of nowhere." This program was enjoyed by students and gave us an approach to standardizing experiences across multiple clinical sites.     

2-O-methylisohemigossylic acid lactone, a sesquiterpene, isolated from roots of mokumen (Gossampinus malabarica) induces cell death and morphological change indicative of apoptotic chromatin condensation in human promyelotic leukemia HL-60 cells

2-O-methylisohemigossylic acid lactone, a sesquiterpene, was purified from roots of mokumen (Gossampinus malabarica) and identified by Mass, and (1)H- and (13)-NMR. This sesquiterpene displayed strong growth inhibitory effect against human promyelotic leukemia HL-60 cells. Apoptotic morphological change of the nucleus, including chromatin condensation was induced in the HL-60 cells treated with the sesquiterpene. The fragmentation of DNA by the sesquiterpene to oligonucleosomal-sized fragments, a characteristic of apoptosis, was observed to be dose- and time-dependent in the HL-60 cells. Inhibitors of caspases suppressed the DNA fragmentation induced by the sesquiterpene. These findings suggest that growth inhibition by the sesquiterpene of HL-60 cells results from the induction of apoptosis by the sesqui-terpene, and that caspase cascade is involved in the induction of apoptosis by the compound in the HL-60 cells.     

Dietary Aspects to Incorporate in the Creation of a Mobile Image-Based Dietary Assessment Tool to Manage and Improve Diabetes

Diabetes is the seventh leading cause of death in United States. Dietary intake and behaviors are essential components of diabetes management. Growing evidence suggests dietary components beyond carbohydrates may critically impact glycemic control. Assessment tools on mobile platforms have the ability to capture multiple aspects of dietary behavior in real-time throughout the day to inform and improve diabetes management and insulin dosing. The objective of this narrative review was to summarize evidence related to dietary behaviors and composition to inform a mobile image-based dietary assessment tool for managing glycemic control of both diabetes types (type 1 and type 2 diabetes). This review investigated the following topics amongst those with diabetes: (1) the role of time of eating occasion on indicators of glycemic control; and (2) the role of macronutrient composition of meals on indicators of glycemic control. A search for articles published after 2000 was completed in PubMed with the following sets of keywords “diabetes/diabetes management/diabetes prevention/diabetes risk”, “dietary behavior/eating patterns/temporal/meal timing/meal frequency”, and “macronutrient composition/glycemic index”. Results showed eating behaviors and meal macronutrient composition may affect glycemic control. Specifically, breakfast skipping, late eating and frequent meal consumption might be associated with poor glycemic control while macronutrient composition and order of the meal could also affect glycemic control. These factors should be considered in designing a dietary assessment tool, which may optimize diabetes management to reduce the burden of this disease.     

多发伤的骨折内固定

目的：认识多发伤中骨折的主要特点,探讨内固定在救治中的意义。方法：回顾1994－08～1999－08间手术救治多发伤66例,对其161处骨折中的98处进行了“仿AO技术”有关方法内固定。结果：骨折均满意愈合;涉及骨折关节51个,功能恢复满意率为96．08％。结论：在多发伤中,骨折、合并伤与并发症远较“一般骨折”复杂、严重;有效固定骨折是一种重要的救命措施;内固定手术应争取在伤后24h进行,但如受条件制约,伤后1－3wk内手术也可获得满意效果;仿AO技术中的某些方法,如拉力螺钉、张力带钢丝及自动加压钢板等,用于内固定可使骨折获得卓有成效的稳定性。