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PubMed1991

Induction of megabase DNA fragments by 5-fluorodeoxyuridine in human colorectal tumor (HT29) cells.

Current evidence suggests that DNA fragmentation plays an integral role in mediating cytotoxicity that results from thymidine nucleotide depletion ("thymineless death"). Recently, Ayusawa et al. [Mutat. Res. 200:221-230 (1988)] reported that dTMP starvation induces cellular processes that result in the release of 50-200-kilobase (kb) DNA fragments in FM3A cells, as detected by pulsed field gel electrophoresis (PFGE). The present study was undertaken to determine whether a similar DNA fragmentation process occurs in a human cell line in response to fluoropyrimidine treatment and, if so, to quantitate this process. When human colorectal tumor (HT29) cells were treated with 100 nm 5-fluorodeoxyuridine (FdUrd), this regimen induced the formation of high molecular weight DNA fragments, which were analyzed using three different PFGE protocols. Field inversion PFGE revealed that, in contrast to the discrete size range reported for FM3A cells, FdUrd-induced fragments in HT29 cells were broadly distributed from about 50 kb to sizes beyond the resolution of the field inversion mode (i.e., greater than 600 kb). Analysis of these same samples by contour-clamped homogeneous electric field PFGE showed that the bulk of these fragments migrated in the 1-5-megabase region. In contrast, fragments from DNA that was broken randomly by gamma-radiation appeared to be primarily in a zone corresponding to approximately 5-10 megabases. Equitoxic FdUrd and radiation treatments (100 nM FdUrd for 48 hr versus 10-Gy gamma-radiation) each increased the fraction of DNA entering the gel from about 0.07-0.09 (untreated cells) to about 0.22-0.25. To a first approximation, the time course and quantity of DNA fragmentation induced by 100 nM FdUrd appeared to correlate with the loss of clonogenicity within the 48-hr period analyzed. These findings suggest that the processes responsible for DNA fragmentation in response to a thymineless state may be different in FM3A and HT29 cells, that in both cases the breaks caused do not appear to be located randomly with respect to the entire genome, and that these processes may be related to the chain of events by which temporary dTMP starvation is made into a lethal insult.

Cell Survival↗
PubMed1996

Serum amyloid A binds specific extracellular matrix glycoproteins and induces the adhesion of resting CD4+ T cells.

Serum amyloid A (SAA), a prototypic acute phase protein reactant, exists naturally in the serum of healthy individuals. However, the levels of SAA in serum and its presence in sites of inflammation increase during certain chronic diseases associated with a local elevation of cytokine concentrations. Although the chemical structure of SAA is defined, its putative immunologic role(s) is still obscure. Nevertheless, it has been shown that 1) SAA acts as a chemoattractant and regulator of the migration of monocytes, polymorphonuclear cells, and T lymphocytes through endothelial cell monolayers; and 2) SAA and its proteolytically degraded N-terminal amyloid A fragment contain an extracellular matrix (ECM)-related cell adhesion epitopes. Herein, we examined whether SAA can associate with specific ECM moieties, and whether immobilized SAA-ECM complexes affect T lymphocyte adhesion. Radiolabeled human rSAA ([125I]rSAA) interacted avidly (Kd = 10(-9) M) and transiently with intact ECM, laminin, and vitronectin, but not with fibronectin or collagen type II. The binding of [125I]rSAA to ECM and laminin was inhibited by unlabeled rSAA and by the AA fragment, but not by the C-terminal portion of SAA (amino acid residues 2-82 and 77-104, respectively). Upon interactions with SAA or amyloid A, immobilized ECM, laminin, and vitronectin induced the adhesion of resting human CD4+ T cells in an apparently beta 1-integrin-mediated manner. Thus, the ECM appears to serve as a temporary anchorage site for SAA and amyloid A, and these ECM-complexed molecules seem to be involved in regulating the recruitment and accumulation of immunocytes in extravascular inflammatory compartments.

Amino Acid Sequence↗
PubMed1988

Counterurbanization: spatial division of labour and regional life-cycles in Canada.

"After a discussion of major concepts of counterurbanization, a narrow definition is proposed. Various demographic and socio-economic dimensions are analysed at different scales with special regard to the Canadian heartland. The basic hypothesis suggests a temporary weakening of urban growth dynamics: decentralization, thus, is a result of locational adjustment strategies, emerging during revolutions in basic technology. The corresponding 'filtering down' processes create a selective, interregional spread of labour. However, shift analytical time series indicate that the development capacity of core regions oscillates in a life-cyclical rhythm. Counterurbanization is expected to fade out with regional adjustment to basic technological transformation."

Americas↗
PubMed1977

Erythropoietic precursors in mice under erythropoietic stimulation and suppression.

Using a methylcellulose clonal cell culture technique, we examined serial changes in erythropoietic precursors in the femur, spleen, and blood of mice prepared with bleeding, erythropoietin injections, or hypertransfusion with packed red blood cells. Significant changes were observed for all hemopoietic organs in the number of erythropoietic burst-forming units (BFU-E) and erythrocytic colony-forming units (CFU-E). In mice prepared with bleeding or erythropoietin injections, the serial changes of BFU-E and CFU-E were similar to but less striking than those seen in mice with phenylhydrazine-induced anemia. The transient decline in the femoral BFU-E coincided with the temporary increase in the splenic and blood BFU-E. A more pronounced increase in CFU-E was noted in the femur and spleen of these mice. In hypertransfused mice, the direction of the changers in the erythropoietic precursors was opposite. While femoral BFU-E increased mildly, a significant drop was noted in the splenic and blood BFU-E. Both femoral and splenic CFU-E declined and remained low while erythrocytosis presisted. Next, we examined the proliferative state of the erythropoietic precursors in the marrow and spleen using short-term incubation with high specific tritiated thymidine. In the marrow and spleen of normal mice, the BFU-E and CFU-E in the DNA synthetic phase was about 36 and 74%, respectively. Neither induction of anemia with phenylhydrazine hydrochloride nor polycythemia with hypertransfusion caused changes in the proliferative state of the precursors. These results indicate that the serial changes in the number of BFU-E represent migration of BFU-E from marrow to spleen rather than BFU-E proliferation. Marrow CFU-E increased in anemic mice and decreased in polycythemic mice without changes in their proliferative state. It is possible that the target of erythropoietic stimulation in mice may be cells at maturational stages intermediate between BFU-E and CFU-E.

Animals↗
PubMed2002

Biliary sphincter motility after neural isolation of the pancreatoduodenal region in conscious dogs.

BACKGROUND: Several neural and hormonal factors are known to affect the motility of the sphincter of Oddi. However, the precise mechanisms of the control of sphincter motility have not been completely explored. We investigated the relationship of canine biliary sphincter motility when it is extrinsically denervated by neural isolation of the pancreatoduodenal region. METHODS: Interdigestive and postprandial sphincter motility in a denervated pancreatoduodenal segment and effects of cholecystokinin-octapeptide were studied in 7 conscious dogs. Data were compared with those of 7 neurally intact control dogs. RESULTS: After extrinsic denervation of the pancreatoduodenal region, sphincter motility exerted a cyclic change in concert with the duodenal myoelectric cycles; this change involved short cyclic bursts of motor activity, which gradually increased in intensity. The increase in the cyclic bursts of motor activity was also cyclic and associated with an increase in the plasma motilin concentration. Neural isolation of the pancreatoduodenal region increased sphincter basal pressure and motility index (integral per minute). In the denervated biliary sphincter, the feeding pattern and temporary inhibitory effect of feeding, as seen in controls, were absent, which suggests the role of extrinsic nerves in delivering bile into the duodenum after feeding. In the denervated dogs, cholecystokinin-octapeptide caused excitation of the sphincter activity, instead of relaxation observed in controls. CONCLUSIONS: Extrinsic innervation to the pancreatoduodenal region has an inhibitory effect on biliary sphincter motility. Abnormalities in extrinsic innervation to the biliary sphincter might increase the resistance of the sphincter to the bile flow and induce bile stagnation.

Animals↗
PubMedDate not supplied

Long-term silastic catheters and chest pain.

There are multiple reports in the literature of vascular erosion in the innominate vein or superior vena cava from the use of temporary central venous catheters. Catheter malposition is likely to precede the development of superior vena cava perforations, a catastrophic complication of central venous catheters. Catheter malposition after initial adequate placement is a very unusual long-term complication and delayed recognition of this complication may have disastrous consequences. Should the catheter change position so the tip is angled toward the sidewall, the repetitive movement of the catheter tip that occurs with respiratory excursion and the cardiac cycle may lead to endothelial injury and eventual erosion of the vein. These problems are thought to be alleviated in the patient receiving long-term intravenous therapy by using a soft Silastic catheter, which may not cause as much damage to the endothelium of the vein. We report three patients with left-sided long-term indwelling Silastic catheters that had changed position over time who presented with chest pain upon infusion of their total parenteral nutrition solutions. In each case, chest x-ray revealed that the tip of the catheter had migrated and was directed against the sidewall of the superior vena cava. In each case, catheter removal and replacement with a new catheter into the right side (subclavian and jugular systems) led to prompt relief of the patient's symptoms.

Aged↗
PubMed2001

Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the rat.

The dentate gyrus is one of the few areas of the mammalian brain where new neurons are continuously produced in adulthood. Certain insults such as epileptic seizures and ischemia are known to enhance the rate of neuronal production. We analyzed this phenomenon using the temporary occlusion of the two carotid arteries combined with arterial hypotension as a method to induce ischemia in rats. We measured the rate of cell production and their state of differentiation with a mitotic indicator, bromodeoxyuridine (BrdU), in combination with the immunohistochemical detection of neuronal markers. One week after the ischemic episode, the cell production in dentate gyrus was increased two- to threefold more than the basal level seen in control animals. Two weeks after ischemia, over 60% of these cells became young neurons as determined by colabeling with BrdU and a cytoplasmic protein (CRMP-4) involved in axonal guidance during development. Five weeks after the ischemia, over 60% of new neurons expressed calbindin, a calcium-binding protein normally expressed in mature granule neurons. In addition to more cells being generated, a greater proportion of all new cells remained in the differentiated but not fully mature state during the 2- to 5-week period after ischemia. The maturation rate of neurons as determined by the calbindin labeling and by the rate of migration from a proliferative zone into the granule cell layer was not changed when examined 5 weeks after ischemia. The results support the hypothesis that survival of dentate gyrus after ischemia is linked with enhanced neurogenesis. Additional physiological stimulation after ischemia may be exploited to stimulate maturation of new neurons and to offer new therapeutic strategies for promoting recovery of neuronal circuitry in the injured brain.

Animals↗
PubMed1993

Cell transplantation of genetically altered cells on biodegradable polymer scaffolds in syngeneic rats.

Many severe metabolic deficiencies in children are caused by a single gene defect with a resultant single gene product deficiency. These diseases may be amenable to permanent cure using new techniques of gene transfer and cell transplantation. In many in vivo models of retroviral mediated gene therapy, a significant limiting factor is the ability to transplant a sufficient number of modified cells. To potentially circumvent this problem, we have developed a biodegradable polymer implant system capable of supporting large numbers of genetically modified cells. In this study, we inserted a reporter gene into syngeneic cultured normal fibroblasts and then transplanted these genetically modified cells into animals using synthetic biodegradable polymer fibers as temporary cell delivery scaffolds. To begin to develop a system capable of delivering desirable proteins secreted by genetically modified cells, Fischer 344 adult rat fibroblasts were transduced in tissue culture with a retrovirus containing the reporter gene Lac Z. These genetically modified cells (1.1 x 10(7) cells/graft) were then attached to the biodegradable polymer fibers and the polymer-cell graft was transplanted subdermally into syngeneic recipients (n = 9). There was persistence of the modified cells with expression of the reporter gene for at least 30 days. The estimated number of genetically modified cells per implanted graft decreased from a pretransplant value of 1.1 +/- 0.6 x 10(7) to 3.2 +/- 0.7 x 10(6) by 15 days after transplantation (P < 0.01). Thereafter, the cell number did not vary significantly to the conclusion of the study at day 30 (3.6 +/- 1.0 x 10(6) cells/graft). Evidence of ingrowth and incorporation of other stromal elements was present in the graft by 1 week post-transplantation, as judged by counterstained hematoxylin and eosin micrograph sections. Migration of modified cells to areas outside of the polymer-cell graft was not detected. Over the course of the study, there was little degradation of the polymer implant, although by day 30, evidence of early dissolution was evident. The number of polymer fibers per high power field increased slightly from 62.5 +/- 5.8 on day 1 to 77.3 +/- 26.6 on day 30 (P > 0.2). These data suggest that the use of biodegradable polymer fibers may permit the transplantation of genetically modified cells in sufficient numbers to deliver a therapeutically useful product. Polymer matrices allow for the attachment and site-specific transplantation of genetically modified cells.

Animals↗
PubMed2004

An in vivo study of hydrogels based on physiologically clotted fibrin-gelatin composites as wound-dressing materials.

In this study we have reported the efficacy of three biomaterials: (a) physiologically clotted fibrin-gelatin composite (PFG), (b) PFG graft copolymerized with 2-hydroxyethyl methacrylate (PFG-HEMA), and (c) PFG graft copolymerized with 2-hydroxypropyl methacrylate (PFG-HPMA) as temporary wound-dressing materials using the rat as an animal model. Full-thickness excision wounds were made on the back of female rats weighing about 150 +/- 10 g. The dressings were applied on the wounds and changed periodically at an interval of 4 days with the respective materials. The wounds treated with PFG-HEMA healed completely on 15th day after wound creation, whereas those treated with PFG and PFG-HPMA resulted in complete healing on the 17th day. The concentrations of collagen, hexosamine, and uronic acid in the granulation tissue were determined. The PFG and its graft copolymers acted as hydrogels, thereby absorbing excess exudates, while still maintaining a moist environment at the wound site. The enhanced wound healing in the experimental animals was reflected in the increased rate of wound contraction. The results of the histological and mechanical studies of the experimental groups revealed that reepithelialization and remodeling of the skin have been achieved by providing a moist environment at the wound site by the biomaterials and thereby hastening the migration of keratinocytes.

Animals↗
PubMed2004

Cartilage and bone tissue engineering for reconstructive head and neck surgery.

The loss of cartilage and bone because of congential defects, trauma and after tumor resection is a major clinical problem in head and neck surgery. The most prevalent methods of tissue repair are through autologous grafting or using implants. Tissue engineering applies the principles of engineering and life sciences in order to create bioartificial cartilage and bone. Most strategies for cartilage tissue engineering are based on resorbable biomaterials as temporary scaffolds for chondrocytes or precursor cells. Clinical application of tissue-engineered cartilage for reconstructive head and neck surgery as opposed to orthopedic applications has not been well established. While in orthopedic and trauma surgery engineered constructs or autologous chondrocytes are placed in the immunoprivileged region of joints, the subcutaneous transplant site in the head and neck can lead to strong inflammatory reactions and resorption of the bioartificial cartilage. Encapsulation of the engineered cartilage and modulation of the local immune response are potential strategies to overcome these limitations. In bone tissue engineering the combination of osteoconductive matrices, osteoinductive proteins such as bone morphogenetic proteins and osteogenic progenitor cells from the bone marrow or osteoblasts from bone biopsies offer a variety of tools for bone reconstruction in the craniofacial area. The utility of each technique is site dependent. Osteoconductive approaches are limited in that they merely create a favorable environment for bone formation, but do not play an active role in the recruitment of cells to the defect. Delivery of inductive signals from a scaffold can incite cells to migrate into a defect and control the progression of bone formation. Rapid osteoid matrix production in the defect site is best accomplished by using osteoblasts or progenitor cells.

Bone and Bones↗
PubMed2001

Evaluation of a spiral nitinol temporary inferior vena caval filter.

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the (a) ability of a prototype temporary inferior vena caval (IVC) filter to trap and retain emboli in an ex vivo flow circuit, (b) feasibility of filter placement and removal via a superficial vein in sheep, and (c) intermediate-term effects of the filter on the insertion vein and at the filter site. MATERIALS AND METHODS: In an iliocaval circuit, embolus capture with the prototype filter was compared to that with a Greenfield filter. In addition, prototype filters were placed into the infrarenal IVC in six sheep. Placement via a superficial venous route was initially attempted. Inferior vena cavography was performed weekly, and filters were removed after 2, 3, or 4 weeks (n = 2 each). Two weeks after the filters were removed, vena cavograms were obtained, the animals were sacrificed, and the IVC was evaluated at pathologic examination. RESULTS: The prototype filter captured all emboli, and the Greenfield filter captured 70%-100% of emboli. Successful placement via a superficial venous route was accomplished in only two sheep owing to small vein caliber; four filters were placed via a deep vein. Adverse events included perifilter thrombus, insertion site infection, and caudal migration. Two sheep died before filter removal owing to sepsis and anesthetic complications. The filters in the remaining four sheep were easily and successfully removed. Five sheep had stenosis at the filter site, and fibrosis with acute and chronic inflammation was seen at microscopic examination. CONCLUSION: The prototype filter trapped emboli as well as the Greenfield filter. Insertion via a superficial route, however, is possible only if the access vein is of an adequate size.

Alloys↗
PubMed1993

Impacts of emigration on mountain watersheds: the upper Pokhara Valley, Nepal.

"Confronted with adverse physical conditions, marginal landholdings and scarce non-farming employment opportunities, farmers in the Upper Pokhara Valley had opted for temporary emigration as an alternative strategy for fulfilling their subsistence requirements. This had caused somewhat malign effects on watershed due to dwindling farm management practices and increasing dependency on common resources.... Findings of this study are envisaged to be conducive to the formulation of a comprehensive watershed management strategy, including population planning....[It is suggested] that both overpopulation and depopulation could be instrumental in watershed degradation, especially in mountainous areas where labor is a critical factor in the use and management of farmlands."

Agriculture↗
PubMed1994

Upregulation of intercellular adhesion molecule 1 (ICAM-1) on brain microvascular endothelial cells in rat ischemic cortex.

The expression of intercellular adhesion molecule 1 (ICAM-1) was studied in rat focal ischemic cortex. A significant increase in ICAM-1 mRNA expression in the ischemic cortex over levels in contralateral (nonischemic) site was observed by means of Northern blot analysis following either permanent or temporary occlusion with reperfusion of the middle cerebral artery (PMCAO or MCAO with reperfusion) in spontaneously hypertensive rats. In the ischemic cortex, levels of ICAM-1 mRNA increased significantly at 3 h (2.6-fold, n = 3, P < 0.05), peaked at 6 to 12 h (6.0-fold, P < 0.01) and remained elevated up to 5 days (2.5-fold, P < 0.05) after PMCAO. The profile of ICAM-1 mRNA expression in the ischemic cortex following MCAO with reperfusion was similar to that following PMCAO, except that ICAM-1 mRNA was significantly increased as early as 1 h (6.3-fold, n = 3, P < 0.05) and then gradually reached a peak at 12 h (12-fold, P < 0.01) after reperfusion. ICAM-1 mRNA expression in ischemic cortex following PMCAO was significantly greater in hypertensive rats than in two normotensive rat strains. Immunostaining using anti-ICAM-1 antibodies indicated that upregulated ICAM-1 expression was localized to endothelial cells of intraparenchymal blood vessels in the ischemic but not contralateral cortex. The data suggest that an upregulation of ICAM-1 mRNA and protein on brain capillary endothelium may play an important role in leukocyte migration into ischemic brain tissue.

Animals↗
PubMed2005

The Jonas study: evaluation of the retrievability of the Cordis OptEase inferior vena cava filter.

PURPOSE: To evaluate the success, safety, and efficacy of the retrieval of the OptEase Permanent/Retrievable Vena Cava Filter (Cordis, Warren, NJ), when implanted for temporary protection against venous thromboembolism. MATERIALS AND METHODS: This prospective, multicenter, non-randomized study enrolled 27 patients who needed temporary protection against pulmonary embolism in whom the intent at the time of filter insertion was retrieval of the OptEase filter. Patients presented with deep venous thrombosis (n = 17), pulmonary embolism (PE) (n = 6), and high risk for PE without thromboembolic disease (n = 4). Assessments included duplex sonography of the access site performed within 24 hours of device implantation and retrieval. All patients underwent cavography before and after filter placement and filter retrieval. Contrast-enhanced computed tomography (CT) of the abdomen and clinical follow-up was performed at 1 month after device retrieval. RESULTS: Of the 27 enrolled patients, 21 patients (77.8%) met the criteria for retrieval and all 21 patients (100%) had filters successfully retrieved with no associated adverse events. Retrieval was not attempted in six patients as a result of ongoing contraindication to anticoagulation (n = 3), large trapped thrombi within the filter (n = 2), and poor patient prognosis (n = 1). Time to retrieval ranged from 5 to 14 days with a mean implantation time of 11.1 days +/- 1.82. No symptomatic pulmonary embolism, vena cava wall injury, vena cava stenosis, significant bleeding, filter fracture, or filter migration was observed. Nineteen of the 21 patients (90.5%) were followed for 1-month post-retrieval with no device-related adverse events or symptomatic PE. Caval patency was documented in 18 of these 19 patients with CT. Two patients were lost to follow-up, and one patient refused to undergo CT examination. CONCLUSION: The OptEase permanent/retrievable vena cava filter can be safely and successfully retrieved up to 14 days in patients who no longer require inferior vena cava filter protection against pulmonary embolism.

Adult↗
PubMedDate not supplied

OptEase retrievable inferior vena cava filter: initial multicenter experience.

The purpose of this article is to describe our experience with the retrievable OptEase inferior vena cava filter (IVCF) (Cordis Corporation, Miami Lakes, FL) in the prevention of pulmonary embolus (PE). Forty patients (24 men, age range 15-85 years, mean age 38 years) who were at temporary risk of PE underwent insertion and retrieval of the OptEase IVCF at two institutions. Eleven patients were treated with filter implantation and subsequent repositioning in the inferior vena cava (IVC) to extend implantation time. All patients were followed up for 24 hours after retrieval, with additional follow-up at the physician's discretion. Forty patients had successful filter insertion. Two patients who underwent intravascular ultrasound guidance for filter deployment required filter repositioning within 24 hours owing to inadvertent placement in the right common iliac vein. All 40 patients underwent successful filter retrieval with no adverse events. In those patients who did not undergo IVCF repositioning, the time to retrieval ranged from 3 to 48 days (mean +/- SD 16.38 +/- 7.20 days). One patient had a successful retrieval at 48 days, but all other retrieval experiences were performed within 23 days. The second strategy involved implantation, with repositioning at least once before final retrieval. This latter strategy occurred in 11 patients, and the time to first capture ranged from 4 to 30 days (mean +/- SD 13.82 +/- 6.13 days). No symptomatic PE, IVC injury or stenosis, significant bleeding, filter fracture, or filter migration was observed. In this feasibility study, the OptEase IVCF prevented symptomatic PE, was safely retrieved or repositioned up to 48 days after implantation, and served as an effective bridge to anticoagulation. In patients who require extended IVCF placement, the OptEase IVCF can be successfully repositioned within the IVC, thereby extending the overall implantation time of this retrievable IVCF.

Adolescent↗
PubMed1992

Predictive factors of effectiveness of streptokinase in deep venous thrombosis.

In a prospective study, 174 patients (118 women and 56 men, average age 44 years, range 14 to 82) with proximal extensive thrombosis received streptokinase (100,000 U/hour) for an average of 2.8 days (range 0.5 to 7) through the catheter of a temporary caval filter. Twenty-seven of 45 (60%) patients with nonocclusive clots were completely free of clots at the second phlebography versus 17 of 116 (14%) with occlusive clots (p less than 0.001). Among nonocclusive clots, proximal ones (caval, iliac and femoral) were more easily lysed than popliteal clots (88 of 116 [76%] vs 26 of 58 [45%]; p less than 0.001). In 41 of 132 (31%) patients, a daily injection of contrast medium through the filter-carrying catheter enabled the observation of a clot in the filter, which was lysed by streptokinase. Seventy patients with follow-up greater than 2 years (median 34 months) were examined clinically. Nineteen of 22 (86%) patients with venograms free of clots at discharge were free of clinical sequelae versus 16 of 48 (33%) without normal venograms (p less than 0.001). It is concluded that: (1) in the case of occlusive clots, only a few patients were normalized after streptokinase; (2) proximal nonocclusive clots were most effectively lysed; (3) when venograms were free of clots at discharge, the majority of patients did not have venous sequelae at follow-up; and (4) embolic migration seems to occur frequently with streptokinase.

Adolescent↗
PubMed2005

Transplanted human embryonic stem cells as biological 'catalysts' for tissue repair and regeneration.

Human embryonic stem cells have tremendous potential in the newly emerging field of regenerative medicine. Recently, it was demonstrated that the rescue of lethal cardiac defects in Id knockout mutant mouse embryos was not due to the transplanted cells giving rise to functional new tissues within the defective embryonic heart. Instead, there is indirect evidence that the observed therapeutic effect was due to various secreted factors emanating from the transplanted cells. This therefore, introduces the exciting prospect of utilizing human embryonic stem cells as biological 'catalysts' to promote tissue repair and regeneration in transplantation therapy. However, the immunological barrier against allogenic transplantation, as well as the teratogenic potential of human embryonic stem cells poses major technical challenges. A possible strategy to overcome the immunological barrier may be to impose a temporary regimen of immunosuppressive drugs followed by their gradual withdrawal, once adequate tissue regeneration has been achieved. Other more novel alternatives include the use of microencapsulation to block interaction with the transplant recipient's immune system, and co-transplantation with bone marrow-derived mesenchymal stem cells, which have been demonstrated to possess immuno-suppressive properties. The teratogenic potential of human embryonic stem cells could possibly be alleviated by directing the differentiation of these cells to specific lineages prior to transplantation, or through mitotic inactivation (gamma irradiation or mitomycin C exposure). Co-transplantation with autologous adult stem cells may represent a novel strategy to further enhance the 'catalytic' effects of human embryonic stem cells. The various factors secreted by human embryonic stem cells could then have a concentrated localized effect on relatively large numbers of co-transplanted autologous adult stem cells, which may in turn lead to enhanced repair and regeneration of the damaged tissue or organ. Moreover, there is also a possibility that synergistic interactions between the co-transplanted human embryonic stem cells and autologous adult stem cells, may somehow produce signals for the recruitment and migration of additional endogenous adult stem cells within the recipient (i.e. peripheral blood circulation, bone marrow), which could further enhance organ/tissue regeneration. Hence, the potential use of human embryonic stem cells as biological 'catalysts' to stimulate tissue repair and regeneration, appears to hold tremendous promise in the field of regenerative medicine. This new therapeutic strategy needs to thoroughly investigated, in view of its potentially important clinical applications.

Adult↗
PubMed1992

Permanent versus temporary rural migrants in Riyadh, Saudi Arabia--a logit analysis of their intentions of future mobility.

"The aim of this paper is to investigate the factors affecting intentions of rural-migrants to return to their rural origins. Several socioeconomic, demographic, spatial, and temporal variables will be introduced to explore their explanatory power and interrelationship with the migrants' intentions. These variables are: Years lived in Riyadh, the current place of parents' residency, land ownership in the village, home ownership in the urban area, income, household size, and the area of origin. The data, which come from a sample survey of migrants conducted in Riyadh in 1983, will be analyzed by the means of binary logit model."

Asia↗