Platelet responses and coagulation activation on polylactide and heparin-polycaprolactone-L-lactide-coated polylactide stent struts

Despite modern stent technology and effective antiplatelet therapy, metallic stents carry the risk of (sub)acute thrombosis. Our aim was to examine short-term differences in platelet deposition and coagulation activation between biodegradable polylactide (PLA), heparin-polycaprolactone-L-lactide-coated polylactide (hepa-P(CL95/L-LA5)-PLA), and stainless steel (SS) stent struts. Gel-filtered platelets (GFP) and platelet-rich plasma (PRP) were labeled with 10 nM (3)H-serotonin. Platelet deposition was measured after incubation of the stent struts in human serum albumin-coated wells at 37 degrees C in either GFP or PRP. Platelet morphology was studied by scanning electron microscopy (SEM). For coagulation activation, the stent struts were incubated in either PRP or platelet-poor plasma (PPP), anticoagulated with D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK), followed by measurement of fibrinogen, thrombin time (TT), prothrombin fragment 1+2 (F1+2), and thrombin-antithrombin complex (TAT). SS showed adherence of larger amounts of GFPs than did PLA at a platelet density of 300 x 10(6)/mL (p < 0.05). Furthermore, representative SEM studies showed more platelet spreading on SS than on PLA stent struts. Between PLA and SS, coagulation activity did not differ at any assessment. Based on prolonged TT values in plasma, the heparin coating strongly inhibited coagulation (p < 0.05). The values of soluble TAT and F1+2 for PLA were similar to those of controls, i.e., to incubated suspensions without a stent strut. In conclusion, when compared with stainless steel, both PLA and hepa-P(CL95/L-LA5)-PLA appear hemocompatible as intravascular stent materials.     

Analysis of the floral transcriptome uncovers new regulators of organ determination and gene families related to flower organ differentiation in Gerbera hybrida (Asteraceae)

Development of composite inflorescences in the plant family Asteraceae has features that cannot be studied in the traditional model plants for flower development. In Gerbera hybrida, inflorescences are composed of morphologically different types of flowers tightly packed into a flower head (capitulum). Individual floral organs such as pappus bristles (sepals) are developmentally specialized, stamens are aborted in marginal flowers, petals and anthers are fused structures, and ovaries are located inferior to other floral organs. These specific features have made gerbera a rewarding target of comparative studies. Here we report the analysis of a gerbera EST database containing 16,994 cDNA sequences. Comparison of the sequences with all plant peptide sequences revealed 1656 unique sequences for gerbera not identified elsewhere within the plant kingdom. Based on the EST database, we constructed a cDNA microarray containing 9000 probes and have utilized it in identification of flower-specific genes and abundantly expressed marker genes for flower scape, pappus, stamen, and petal development. Our analysis revealed several regulatory genes with putative functions in flower-organ development. We were also able to associate a number of abundantly and specifically expressed genes with flower-organ differentiation. Gerbera is an outcrossing species, for which genetic approaches to gene discovery are not readily amenable. However, reverse genetics with the help of gene transfer has been very informative. We demonstrate here the usability of the gerbera microarray as a reliable new tool for identifying novel genes related to specific biological questions and for large-scale gene expression analysis.     

Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency

BACKGROUND: Common variable immunodeficiency (CVID) is a primary immune disorder characterized by antibody deficiency and a decrease in serum IgG and IgA, IgM, or both levels at least 2 SDs below the mean for age and not attributed to other known immunologic disorders. These patients often present with frequent and severe episodes of pneumonia before diagnosis. The standard treatment, intravenous immunoglobulin (IVIG), has been available for the past 20 years. No large-scale study has compared the incidence of pneumonia in these patients before and after IVIG treatment. OBJECTIVE: The aim of this study was to document the effectiveness of intravenous immunoglobulin treatment on the incidence of pneumonia in patients with CVID. METHODS: We performed chart reviews and interviews of patients with laboratory-confirmed CVID seen at our clinical center. The number of episodes of pneumonia was documented before and after treatment with immunoglobulin replacement therapy. RESULTS: The histories of 50 patients were reviewed (mean current age, 42 +/- 16.3 years; age range, 10-78 years; 20 male and 30 female patients). Forty-two (84%) of the 50 patients with CVID had pneumonia at least once before receiving immunoglobulin treatment, and 11 of 42 of these patients had multiple episodes. After treatment with gamma globulin over a mean period of 6.6 +/- 5.2 years (range, <1-20 years), the number of patients experiencing pneumonia significantly decreased to 11 (22%) of 50. In most cases these patients had pneumonia in the first year of immunoglobulin treatment. CONCLUSION: The treatment of CVID with IVIG significantly reduces the incidence of pneumonia.     

Web-based virtual microscopy in teaching and standardizing Gleason grading

Gleason grading forms the basis of prognostic and therapeutic assessment in prostatic carcinoma despite its subjective nature and substantial interobserver variation. The accuracy of Gleason grading can be improved by the use of educational tools such as reference images. However, conventional microscopy images are of limited educational value because it is neither possible to view the sample at different magnifications nor to navigate into different areas of the specimen. This limitation can be overcome by the use of virtual microscopy, which allows viewing entire digitized microscope slides. We created an interactive Web site ( www.webmicroscope.net/gleason ) featuring a comprehensive set of prostatic needle biopsies as virtual slides, which can be viewed with a standard Web browser (Internet Explorer or Netscape). To evaluate the validity of Web-based virtual microscopy for Gleason grading, an experienced uropathologist (TK) scored a series of 62 biopsies from the original glass slides and 6 weeks later from virtual slides on the Web site using an ordinary desktop computer. The intraobserver agreement was excellent, with identical Gleason scores found in 48 of the 62 cases ( kappa = 0.73). The 14 remaining scores differed only by 1 point on the Gleason scale (2-10). The virtual slides were viewed by 2 other uropathologists (PM and HH), with interobserver kappa coefficients ranging from 0.55 to 0.62, which is within the range of previously reported studies using glass slides. The 3 uropathologists' Gleason scores were included as reference scores on the Web site, which now serves as a publicly open platform for self-testing and learning of Gleason grading. We conclude that Web-based virtual microscopy is a promising new tool for teaching and standardizing Gleason grading.     

High levels of interleukin-1 in patients with endemic pemphigus foliaceus

Endemic pemphigus foliaceus (EPF) is an autoimmune disease characterized by blister formation with a loss of cohesion and infiltration of inflammatory cells. We observed that supernatants of peripheral blood mononuclear cells from patients produced significantly more interleukin-1beta (IL-1beta) than those from stimulated healthy controls. Furthermore, a Th2 bias was observed in EPF patients when the IL-5/gamma interferon ratio was analyzed. These results indicate that cells from pemphigus patients react with a vigorous proinflammatory response.     

Deletion of RBM and DAZ in azoospermia: Evaluation by PRINS

Molecular and cytogenetic studies from infertile men have shown that one or more genes controlling spermatogenesis are located in proximal Yq11.2 in interval 6 of the Y chromosome. Microdeletions within the azoospermia factor region (AZF) are often associated with azoospermia and severe oligospermia in men with idiopathic infertility. We evaluated cells from a normal‐appearing 27‐year‐old man with infertility and initial karyotype of 45,der(X)t(X;Y)(p22.3;p11.2)[8]/46,t(X;Y)(p22.3;p11.2)[12]. By fluorescence in situ hybridization with dual‐color whole chromosome paint probes for X and Y chromosomes, we confirmed the Xp‐Yp interchange. By primed in situ labeling, we identified translocation of the SRY gene from its original location on Yp to the patient's X chromosome at band Xp22. We also obtained evidence that the apparent marker was a der(Y) (possibly a ring) containing X and Y domains, and observed that the patient's genome was deleted for RBM and DAZ, two candidate genes for AZF. © 2001 Wiley‐Liss, Inc.     

Comparison of anatomical location of squamous cell carcinoma within the oral cavity and oropharynx with the incidence of in vitro hyperdiploidy

The anatomical location of the squamous cell carcinoma (SCCA) within the oral cavity and oropharynx influenced the association of SCCA with the biomarker in vitro hyperdiploidy in human dermal fibroblast cultures (IVH). There was a strong association of IVH with the occurrence of SCCA in the anterior 2/3 of the tongue, floor of the mouth and lower alveolar ridge of the oral cavity and in the base of the tongue and pharyngeal wall of the oropharynx. There was a lower association of SCCA with IVH in the tonsillar region of the oropharynx. IVH showed no association with SCCA located in other anatomical parts of the oral region. The patient group whose diagnosis of SCCA in the anterior 2/3 of the tongue occurred prior to the age of 50 years were invariably IVH-, whereas those diagnosed after the age of 50 years were IVH+, providing evidence for heterogeneity. There was no such correlation of biomarker subgrouping with age of diagnosis demonstrated for SCCA at any other anatomical location within the oral cavity or oropharynx.     

Safety of antiretroviral prophylaxis of perinatal transmission for HIV-infected pregnant women and their infants

Worldwide, more than 1600 infants become infected with HIV each day. Almost all infections are a result of mother-to-child transmission of HIV, with most of these infections occurring in resource-poor countries. In developed countries, antiretroviral prophylaxis has dramatically reduced perinatal transmission to <2%. The potential now exists to extend this success to resource-poor countries using effective but shorter and less expensive antiretroviral regimens.With the potential widespread use of antiretroviral therapy for perinatal HIV prevention in resource-limited settings, there will be exposure of increasing numbers of infants to in utero and postpartum antiretroviral drugs for which long-term toxicity data is unknown. This article focuses on a review of what is known about safety of antiretroviral regimens used to interrupt mother-to-child transmission for women and their children.     

Multiple Separations in Microfabricated Channels: From Biological Microenvironments to DNA

A continuous sample introduction and separation scheme is presented as an alternative to the current slab gel and microfabricated chip technologies for biological separations. This new technique involves continuous sample introduction via a conventional small bore capillary coupled to a small dimension rectangular channel. Both free zone and size based separations have been carried out in the rectangular channel. Laser induced fluorescence and electrochemical detection schemes have been employed with this technique. Some of the areas this technology has been used to investigate include monitoring dynamic events from microenvironments, monitoring analytes over long periods of time, and performing DNA separations.     

IL-4–BATF signaling directly modulates IL-9 producing mucosal mast cell (MMC9) function in experimental food allergy

1. Download : Download high-res image (233KB)
2. Download : Download full-size image