Home About us Contact
|
Home About us Contact | ||
|
|
||
Ectopic Sites (ectopic + site)
Selected AbstractsHuman islet cell transplantation , future prospectsDIABETIC MEDICINE, Issue 2 2001S. A. White Summary Background Islet transplantation has the potential to cure diabetes mellitus. Nevertheless despite successful reversal of diabetes in many small animal models, the clinical situation has been far more challenging. The aim of this review is to discuss why insulin-independence after islet allotransplantation has been so difficult to achieve. Methods A literature review was undertaken using Medline from 1975 to July 2000. Results reported to the International Islet Transplant Registry (ITR) up to December 1998 were also analysed. Results Up to December 1998, 405 islet allotransplants have been reported the ITR. Of those accurately documented between 1990 and 1998 (n = 267) only 12% have achieved insulin-independence (greater than 7 days). However with refined peri-transplant protocols insulin indepedence at 1 year can reach 20%. Conclusions There are many factors which can explain the failure of achieving insulin-independence after islet allotransplantation. These include the use of diabetogenic immunosuppressive agents to abrogate both islet allo-immunity and auto-immunity, the critical islet mass to achieve insulin-independence and the detrimental effects of transplanting islets in an ectopic site. However recent evidence most notably from the Edmonton group demonstrates that islet allotransplantation still has great potential to become an established treatment option for diabetic patients. [source] A subpopulation of mesenchymal stromal cells with high osteogenic potentialJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Hua Liu Abstract Current bone disease therapy with bone marrow-derived mesenchymal stromal cells (MSC) is hampered by low efficiency. Advanced allogeneic studies on well-established mouse genetic and disease models are hindered by difficulties in isolating murine MSC (mMSC). And mMSC prepared from different laboratories exhibit significant heterogeneity. Hence, this study aimed to identify and isolate a sub-population of mMSC at an early passage number with high osteogenic potential. Enrichment of mMSC was achieved by 1-hr silica incubation and negative selection. Approximately 96% of these cells synthesized osteocalcin after 28 days of osteogenic induction in vitro, and displayed a complete dynamic alteration of alkaline phosphatase (ALP) activity with increasing osteogenic maturation and strong mineralization. Moreover, the cells displayed uniform and stable surface molecular profile, long-term survival, fast proliferation in vitro with maintenance of normal karyotype and distinct immunological properties. CD73 was found to be expressed exclusively in osteogenesis but not in adipogenesis. These cells also retained high osteogenic potential upon allogeneic transplantation in an ectopic site by the detection of bone-specific ALP, osteopontin, osteocalcin and local mineralization as early as 12 days after implantation. Hence, these cells may provide a useful source for improving current strategies in bone regenerative therapy, and for characterizing markers defining the putative MSC population. [source] Chick limbs with mouse teeth: An effective in vivo culture system for tooth germ development and analysisDEVELOPMENTAL DYNAMICS, Issue 1 2003Eiki Koyama Abstract Mouse tooth germ development is currently studied by three main approaches: in wild-type and mutant mouse lines, after transplantation of tooth germs to ectopic sites, and in organ culture. The in vivo approaches are the most physiological but do not provide accessibility to tooth germs for further experimental manipulation. Organ cultures, although readily accessible, do not sustain full tooth germ development and are appropriate for short-term analysis. Thus, we sought to establish a new approach that would combine experimental accessibility with sustained development. We implanted fragments of embryonic day 12 mouse embryo first branchial arch containing early bud stage tooth germs into the lateral mesenchyme of day 4,5 chick embryo wing buds in ovo. Eggs were reincubated, and implanted tissues were examined by histochemistry and in situ hybridization over time. The tooth germs underwent seemingly normal growth, differentiation, and morphogenesis. They reached the cap, bell, and crown stages in approximately 3, 6, and 10 days, respectively, mimicking in a striking manner native temporal patterns. To examine mechanisms regulating tooth germ development, we first implanted tooth germ fragments, microinjected them with neutralizing antibodies to the key signaling molecule Sonic hedgehog (Shh), and examined them over time. Tooth germ development was markedly delayed, as revealed by poor morphogenesis and lack of mature ameloblasts and odontoblasts displaying characteristic traits such as an elongated cell shape, nuclear relocalization, and amelogenin gene expression. These phenotypic changes began to be reversed upon further incubation. The data show that the limb bud represents an effective, experimentally accessible as well as economical system for growth and analysis of developing tooth germs. The inhibitory effects of Shh neutralizing antibody treatment are discussed in relation to roles of this signaling pathway proposed by this and other groups previously. © 2002 Wiley-Liss, Inc. [source] Spatial Distribution and Frequency Dependence of Arrhythmogenic Vagal Effects in Canine AtriaJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2000OLEG F. SHARIFOV Ph.D. Arrhythmogenic Vagal Effects in Dog Atria. introduction: Prior studies in isolated canine atria demonstrated that acetylcholine-induced reentrant atrial fibrillation (AF) was triggered by multifocal activity in the area of normal impulse origin (sinus node-crista terminalis). The aim of this study was to investigate the activation sequence in AF induced by vagal stimulation (VS) in intact dog hearts. Methods and Results: VS (10 to 50 Hz, 1 msec, 15 V, 5-sec trains) induced single or multiple atrial premature depolarizations (APDs), and/or AF in 8 of 10 open chest dogs. Occurrence of APDs and AF increased with increasing VS intensity. Epicardial mapping (254 unipolar electrodes) of both atria showed that APDs as a rule emerged from ectopic sites, often from the right atrial appendage. Activation mapping of the first 10 cycles of AF showed that only a small number (<3 to 4) of unstable reentrant circuits were possible at the same moment. Moreover, most sustained VS-induced AFs were accounted for by a single leading stable reentrant circuit that activated the remainder of the atria. Conclusion: (1) Occurrence of vagally induced APDs and AF increases with increasing frequency of VS. (2) VS-induced focal ectopic APDs are widely distributed over the atria. (3) A single APD can be sufficient for initiation of reentrant AF. (4) Despite its high rate of sustained AF, it may be maintained by single stable reentrant circuit. (5) The atrial septum can play an important role in both the initiation and the maintenance of VS-induced AF. [source] Assessment of progestin-only therapy for endometriosis in macaqueJOURNAL OF MEDICAL PRIMATOLOGY, Issue 2008G. Maginnis Abstract Background, Endometriosis is a condition where endometrium-like tissue forms lesions at ectopic sites outside the uterus. In women, oral contraceptive pills and progestins are often prescribed as therapy for early stage endometriosis. In contrast, in macaques the disease is frequently advanced at the time of diagnosis and ovariectomy is the standard therapy. However, surgery is contraindicated in many patients. A review of 15 endometriosis cases over the past 10 years at the Oregon National Primate Research Center (ONPRC) revealed that 5 failed to show improvement after ovariectomy and were subsequently euthanized. Therefore, our goal was to assess the feasibility of treating endometriosis in macaques with chronic progesterone (P) as an alternative therapy for the disease. Methods, Seven adult rhesus macaques with advanced endometriosis were identified by clinical symptoms and endometriosis was confirmed by abdominal palpation, ultrasound examination, and/or aspiration of menstrual blood from abdominal cysts. The patients were chronically treated with Silastic capsules that released 5,7 ng P /ml in blood for up to 20 months. During treatment the patients were assessed daily and scored numerically for appetite, activity, attitude, abdominal discomfort and menstruation by the Clinical Veterinary staff. The patients were then re-examined by abdominal palpation and ultrasound for the disease at the end of treatment. Results, During the first 2 weeks of treatment, endometriotic symptoms improved significantly in all the patients (P < 0.05). This was associated with a significant increase in body weight and significant reduction in abdominal discomfort and menstrual bleeding. Two of the patients gradually developed increased symptoms of the disease after 5 months of treatment. Post-treatment abdominal examination revealed that 2/5 patients continued to have an abdominal mass even though symptoms were suppressed. Conclusions, We conclude that continuous P treatment of rhesus monkeys provides therapeutic benefit to reduce symptoms of endometriosis and may provide an option for cases where ovariectomy is contraindicated. Supported by RR-00163. [source] Bipolar localization of the group II intron Ll.LtrB is maintained in Escherichia coli deficient in nucleoid condensation, chromosome partitioning and DNA replicationMOLECULAR MICROBIOLOGY, Issue 3 2006Arthur Beauregard Summary Group II introns are mobile genetic elements that invade their cognate intron-minus alleles via an RNA intermediate, in a process known as retrohoming. They can also retrotranspose to ectopic sites at low frequency. In Escherichia coli, retrotransposition of the lactococcal group II intron, Ll.LtrB, occurs preferentially within the Ori and Ter macrodomains of the E. coli chromosome. These macrodomains migrate towards the poles of the cell, where the intron-encoded protein, LtrA, localizes. Here we investigate whether alteration of nucleoid condensation, chromosome partitioning and replication affect retrotransposition frequencies, as well as bipolar localization of the Ll.LtrB intron integration and LtrA distribution in E. coli. We thus examined these properties in the absence of the nucleoid-associated proteins H-NS, StpA and MukB, in variants of partitioning functions including the centromere-like sequence migS and the actin homologue MreB, as well as in the replication mutants ,oriC, seqA, tus and topoIV,ts. Although there were some dramatic fluctuations in retrotransposition levels in these hosts, bipolar localization of integration events was maintained. LtrA was consistently found in nucleoid-free regions, with its localization to the cellular poles being largely preserved in these hosts. Together, these results suggest that bipolar localization of group II intron retrotransposition results from the residence of the intron-encoded protein at the poles of the cell. [source] Conjugation mediates transfer of the Ll.LtrB group II intron between different bacterial speciesMOLECULAR MICROBIOLOGY, Issue 5 2004Kamila Belhocine Summary Some self-splicing group II introns (ribozymes) are mobile retroelements. These retroelements, which can insert themselves into cognate intronless alleles or ectopic sites by reverse splicing, are thought to be the evolutionary progenitors of the widely distributed eukaryotic spliceosomal introns. Lateral or horizontal transmission of introns (i.e. between species), although never experimentally demonstrated, is a well-accepted model for intron dispersal and evolution. Horizontal transfer of the ancestral bacterial group II introns may have contributed to the dispersal and wide distribution of spliceosomal introns present in modern eukaryotic genomes. Here, the Ll.LtrB group II intron from the Gram-positive bacterium Lactococcus lactis was used as a model system to address the dissemination of introns in the bacterial kingdom. We report the first experimental demonstration of horizontal transfer of a group II intron. We show that the Ll.LtrB group II intron, originally discovered on an L. lactis conjugative plasmid (pRS01) and within a chromosomally located sex factor in L. lactis 712, invades new sites using both retrohoming and retrotransposition pathways after its transfer by conjugation. Ll.LtrB lateral transfer is shown among different L. lactis strains (intraspecies) (retrohoming and retrotransposition) and between L. lactis and Enterococcus faecalis (interspecies) (retrohoming). These results shed light on long-standing questions about intron evolution and propagation, and demonstrate that conjugation is one of the mechanisms by which group II introns are, and probably were, broadly disseminated between widely diverged organisms. [source] The role of double-strand break-induced allelic homologous recombination in somatic plant cellsTHE PLANT JOURNAL, Issue 3 2002Brigitte Gisler Summary During meiosis, homologous recombination occurs between allelic sequences. To evaluate the biological significance of such a pathway in somatic cells, we used transgenic tobacco plants with a restriction site for the rare cutting endonuclease I- SceI within a negative selectable marker gene. These plants were crossed with two tobacco lines containing, in allelic position, either a deletion or an insertion within the marker gene that rendered both marker gene and restriction site inactive. After the double-strand break induction, we selected for repair events resulting in a loss of marker gene function. This loss was mostly due to deletions. We were also able to detect double strand break-induced allelic recombination in which the break was repaired by a faithful copying process from the homologue carrying the shortened transgene. The estimated frequency indicates that homologous recombination in somatic cells between allelic sites appears to occur at the same order of magnitude as between ectopic sites, and is thus far too infrequent to act as major repair pathway. As somatic changes can be transferred to the germ line, the prevalence of intrachromatid rearrangements over allelic recombination might be an indirect prerequisite for the enhanced genome plasticity postulated for plants. [source] | |||||||||||||