Umbilical cord blood (CB) stem cells have been proposed for cell-based therapeutic applications for diverse diseases of the CNS. We hypothesized that tissue-engineering strategies may extend the efficacy of these approaches by improving the long-term viability and function of stem cell-derived neuronal progenitors. To test our hypothesis, we explored the survival and differentiation of human CB-derived neuronal progenitors (HUCBNP) in a three-dimensional (3D) collagen construct. In contrast to two-dimensional culture conditions, the cells survived in 3D for an extended period of time of more than 2 months. Under 3D conditions, HUCBNP underwent spontaneous neuronal differentiation, which was further enhanced by treatment with neuronal conditioned medium (CM) and nerve growth factor (NGF). Neurite outgrowth, quantified by assessing the fractal dimension (Df) of the complex neuronal networks, was significantly enhanced under 3D conditions in the presence of CM/NGF, concomitant with a reduced expression of the early neuronal marker nestin (1.9-fold), and increased levels of mature neuronal markers such as MAP-2 (3.6-fold), β-tubulin (1.5-fold), and neuronal specific enolase (6.6-fold) and the appearance of the synaptic marker synaptophysin. To assess the feasibility for clinical usage, HUCBNP were also isolated from frozen CB samples and cultured under 3D conditions. The data indicate the essential complete preservation of neurotrophic (survival) and neurotropic (neurite outgrowth) properties. In conclusion, 3D culture conditions are proposed as an essential step for both maintenance of CB neuronal progenitors in vitro and for investigating specific features of neuronal differentiation towards future use in regenerative therapy. 相似文献
Fibroblastic/myofibroblastic neoplasms represent a broad, and occasionally diagnostically challenging, category of soft tissue neoplasms. A subset of these tumors defy conventional classification. However, with the advent of next‐generation sequencing, the identification of disease‐defining molecular alterations is gradually improving their subclassification. Following identification of two index cases of a distinctive fibroblastic neoplasm with a fusion gene involving PRRX1 and NCOA1, we performed a retrospective review to further characterize this entity. We identified two additional cases, including one with a fusion between PRRX1 and NCOA2. The average patient age was 38 years, and three patients were female. Two tumors occurred on the neck, and the others involved the groin and thigh. Tumors were centered in the subcutis and ranged from 2.3 to 14.0 cm (average 5.8 cm). Morphologically, they were predominantly hypocellular, with focal hypercellularity. They were composed of monomorphic spindle‐stellate cells with a vague fascicular pattern. The nuclei were bland with only rare mitotic activity, and occasional multinucleation. The intervening stroma was typically abundant and ranged from myxoid to collagenous, with frequent rope‐like collagen bundles. Three of the cases had a prominent vasculature ranging from numerous small curvilinear vessels to ectatic and branching staghorn‐like vessels. Immunohistochemistry was negative for desmin, smooth muscle actin, S100, CD34, keratin, and epithelial membrane antigen. Each of the patients was treated by simple excision and none of the tumors were associated with local recurrence or metastasis. Based on their unique morphological and molecular attributes, we believe this represents a novel fibroblastic tumor for which we have tentatively proposed the name “PRRX‐NCOAx‐rearranged fibroblastic tumor.” 相似文献
Objectives. We attempted to determine the correlation between the presence of postextrasystolic changes in the STU segment and a history of sustained ventricular arrhythmias.
Background. Postextrasystolic U wave augmentation (a marked increment in U wave amplitude after premature ventricular complexes [PVCs]) is an adverse prognostic sign in the “pause-dependent long QT syndrome.” However, the prevalence of postextrasystolic changes in patients without the long QT syndrome is unknown.
Methods. We compared the configuration of the STU segment of the postextrasystolic beat (the sinus beat after a PVC) with the STU configuration during sinus rhythm in three patient groups: 1) 41 patients with spontaneous ventricular tachycardia/fibrillation (VT/VF) (VT/VF group), 2) 63 patients with heart disease and high grade ventricular arrhythmias (control group), and 3) 29 patients with high grade ventricular arrhythmias but no heart disease (reference group).
Results. Postextrasystolic T wave changes did not correlate with a history of ventricular tachyarrhythmias. However, postextrasystolic U wave changes were more common among the patients with VT/VF than among control subjects (39% vs. 8.7%, p < 0.001). By logistic multiple regression analysis, a low left ventricular ejection fraction (p < 0.001) and postextrasystolic U wave changes (p < 0.005) were independent predictors of ventricular tachyarrhythmias.
Conclusions. Postextrasystolic T wave changes are common and lack predictive value. Postextrasystolic U wave changes may be a specific marker of a tendency to the development of spontaneous ventricular arrhythmias. Prospective studies should be performed to confirm this association.
Summary We present a case of a subtrochanteric fracture that occurred 1 week after the surgical treatment of a Garden 1 Type subcapital fracture by way of pinning in situ with multiple Knowles pins. The event took place in the patient's bed with no evidence of trauma of any kind. The fracture line went through the insertion site of the lower (distal) pin. This rare type of complication was successfully treated by revision surgery and fixation of both fractures by way of a Richard's dynamic hip screw. We review the literature with regard to the incidence, the possible etiological factors involved and the recommended modes or treatment. 相似文献
Background: Prostaglandins (PGs) were shown in vitro to suppress several functions of cellular immunity. It is unclear, however, whether physiological levels of PGs can suppress cellular immunity in vivo and whether such suppression would compromise postoperative host resistance to metastasis.Methods: Fischer 344 rats were administered PGE2 in doses (18 to 300 g/kg subcutaneously) that increased the serum levels approximately 2- to 4-fold. We then assessed the number and activity of circulating natural killer (NK) cells, as well as rats resistance to experimental metastasis of a syngeneic NK-sensitive tumor (MADB106). To study whether endogenously released PGs after surgery compromise these indices, we tested whether laparotomy adversely affects them and whether a cyclooxygenase-synthesis inhibitor, indomethacin (4 mg/kg), attenuates these effects.Results: PGE2 dose-dependently suppressed NK activity per NK cell and dose-dependently increased 4- and 24-hour MADB106 lung tumor retention (LTR); 240 g/kg of PGE2 quadrupled the number of lung metastases counted 3 weeks later. Selective depletion of NK cells abrogated the promotion of LTR by PGE2. Surgery significantly suppressed NK activity and increased MADB106 LTR, and indomethacin halved these effects without affecting nonoperated rats.Conclusions:PGE2 is a potent in vivo suppressor of NK activity, and its postoperative release may promote tumor recurrence. 相似文献
Beta-cell replacement is considered to be the most promising approach for treatment of type 1 diabetes. Its application on a large scale is hindered by a shortage of cells for transplantation. Activation of insulin expression, storage, and regulated secretion in stem/progenitor cells offers novel ways to overcome this shortage. We explored whether fetal human progenitor liver cells (FH) could be induced to differentiate into insulin-producing cells after expression of the pancreatic duodenal homeobox 1 (Pdx1) gene, which is a key regulator of pancreatic development and insulin expression in beta cells. FH cells possess a considerable replication capacity, and this was further extended by introduction of the gene for the catalytic subunit of human telomerase. Immortalized FH cells expressing Pdx1 activated multiple beta-cell genes, produced and stored considerable amounts of insulin, and released insulin in a regulated manner in response to glucose. When transplanted into hyperglycemic immunodeficient mice, the cells restored and maintained euglycemia for prolonged periods. Quantitation of human C-peptide in the mouse serum confirmed that the glycemia was normalized by the transplanted human cells. This approach offers the potential of a novel source of cells for transplantation into patients with type 1 diabetes. 相似文献
Pituitary - In adults and children, transsphenoidal surgery (TSS) represents the cornerstone of management for most large or functioning sellar lesions with the exception of prolactinomas.... 相似文献