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PubMed2000

The turmoil of aboriginal enumeration: mobility and service population analysis in a central Australian community.

This paper documents Aboriginal population change and mobility over time in a remote community in central Australia. The movement of population has implications for service delivery and resource allocation. Aboriginal population in the region is characterised by high mobility. We conducted four population surveys in a selected remote community over a 12 month period and categorised individuals into four mutually exclusive groups: residents, dual residents, visitors and absent residents. Based on these categories we developed two population classifications: actual and potential service populations. The potential service population was consistently higher than the Australian Bureau of Statistics (ABS) census figure. We question the use of ABS census estimates as appropriate population figures for determining resource allocation to remote communities. We quantify inter- and intra-community mobility. When the potential population is used as denominator, 35% of the population of this community was classified as inter-community mobile. Given this level of mobility we argue that: (1) Resources should be allocated to compensate health services for the additional time and resource requirements to deal with the high level of population mobility. (2) Health programs such as STD control, trachoma, scabies and other communicable diseases common in Central Australia should be coordinated and delivered as regional programs often crossing State/Territory borders.

Australia↗
PubMed2001

Mechanisms of thrombotic microangiopathy following xenogeneic hematopoietic progenitor cell transplantation.

INTRODUCTION: Attempts to induce tolerance though mixed hematopoietic chimerism in the discordant pig-to-baboon xenotransplantation model are sometimes complicated by a potentially fatal thrombotic microangiopathy in the recipient baboons. This state develops immediately after the infusion of porcine mobilized peripheral blood leukocytes, containing progenitor cells (PBPC). In our study, we examined the interaction of infused porcine PBPC with recipient platelets in vivo in baboons and investigated the underlying mechanisms using an in vitro model. METHODS: Two naïve baboons and six baboons preconditioned with irradiation and immunosuppression that received porcine PBPC were evaluated in vivo. The interaction of porcine and baboon PBPC with baboon platelets was investigated by an in vitro platelet aggregation assay. Fresh and cryopreserved PBPC were evaluated as well as PBPC obtained from growth-factor mobilized and unmobilized pigs. Furthermore, cellular subsets of PBPC were assessed for potential to induce platelet aggregation. Immunohistochemical staining was performed on platelet-leukocyte aggregates and potential inhibition of aggregation with anti-P-selectin and anti-CD154 mAbs, or eptifibatide (a GPIIb/IIIa receptor antagonist), was tested. RESULTS: All baboons that received porcine PBPC rapidly developed marked thrombocytopenia (<20,000/microl), elevated serum lactate dehydrogenase (>1,500U/liter), schistocytosis, and platelet aggregates on blood smear. Three baboons died (two untreated and one preconditioned), and substantive platelet aggregates containing porcine leukocytes were observed in the microvasculature of lungs and kidneys. In vitro, porcine, but not baboon, PBPC induced aggregation of baboon platelets in a dose-dependent manner. Immunohistological examination of these aggregates confirmed the incorporation of porcine leukocytes. Cryopreserved PBPC caused less aggregation than fresh PBPC, and growth-factor-mobilized PBPC induced less aggregation than unmobilized PBPC. Aggregation was fully abrogated by the addition of eptifibatide, and modulated by anti-P-selectin and anti-CD154 monoclonal antibodies that recognize adhesion receptors on activated platelets. Purified fractions (granulocytes, CD2+, and CD- cells) of porcine PBPC did not initiate aggregation, whereas addition of exogenous porcine PBPC membranes (erythrocytes, dead cells, and/or platelets) to the purified fractions exacerbated the aggregation response. CONCLUSIONS: These data indicate that porcine PBPC mediate aggregation of baboon platelets. This process likely contributes to the thrombotic microangiopathy observed after PBPC transplantation in the pig-to-baboon model. Eptifibatide can fully abrogate platelet aggregation induced by porcine PBPC in vitro. Purification of the progenitor cells from porcine PBPC and/or treatment of baboons with eptifibatide may be beneficial.

Animals↗
PubMed2003

Modulation of the electrophoretic mobility of the linker for activation of T cells (LAT) by the calcineurin inhibitors CsA and FK506: LAT is a potential substrate for PKC and calcineurin signaling pathways.

The linker for activation of T cells (LAT) is essential for T cell activation. Cyclosporin A (CsA) and FK506, inhibitors of T cell proliferation, have been very useful for preventing autoimmune and inflammatory disease and graft rejection. However, both compounds are associated with side effects. We show that TCR ligation in the presence of FK506 or CsA induced rapid modifications in LAT that modulate the electrophoretic mobility of the molecule in SDS-PAGE. Calcineurin, a target for CsA and FK506, dephosphorylated LAT in vitro and restored its electrophoretic mobility. Stimulating T cells with the protein kinase C (PKC) activator PMA induced a shift in the mobility of LAT, whereas inhibitors of PKC blocked the effect of PMA. Thus, manipulating calcineurin or PKC activation alters the electrophoretic mobility of LAT. These results shed light on the molecular actions of CsA and FK506 in T cells and implicate LAT in mediating the drugs' actions.

Adaptor Proteins, Signal Transducing↗
PubMed2007

Future investigations in stem cell activation with granulocyte-colony-stimulating factor after myocardial infarction.

Experimental data indicate that stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) might have potential as a novel therapeutic strategy for acute myocardial infarction. The prospective beneficial effects of G-CSF can be attributed mainly to a direct action on injured myocardium rather than on differentiation of mobilized bone marrow stem cells into cardiac myocytes. This article reviews the evidence for the potential cardioprotective effects of G-CSF and discusses future investigations regarding pharmacologic stem cell activation and mobilization with G-CSF in the setting of acute myocardial infarction.

Animals↗
PubMed1993

Charges, currents, and potentials in ionic channels of one conformation.

Flux through an open ionic channel is analyzed with Poisson-Nernst-Planck (PNP) theory. The channel protein is described as an unchanging but nonuniform distribution of permanent charge, the charge distribution observed (in principle) in x-ray diffraction. Appropriate boundary conditions are derived and presented in some generality. Three kinds of charge are present: (a) permanent charge on the atoms of the protein, the charge independent of the electric field; (b) free or mobile charge, carried by ions in the pore as they flux through the channel; and (c) induced (sometimes called polarization) charge, in the pore and protein, created by the electric field, zero when the electric field is zero. The permanent charge produces an offset in potential, a built-in Donnan potential at both ends of the channel pore. The system is completely solved for bathing solutions of two ions. Graphs describe the distribution of potential, concentration, free (i.e., mobile) and induced charge, and the potential energy associated with the concentration of charge, as well as the unidirectional flux as a function of concentration of ions in the bath, for a distribution of permanent charge that is uniform. The model shows surprising complexity, exhibiting some (but not all) of the properties usually attributed to single filing and exchange diffusion. The complexity arises because the arrangement of free and induced charge, and thus of potential and potential energy, varies, sometimes substantially, as conditions change, even though the channel structure and conformation (of permanent charge) is strictly constant. Energy barriers and wells, and the concomitant binding sites and binding phenomena, are outputs of the PNP theory: they are computed, not assumed. They vary in size and location as experimental conditions change, while the conformation of permanent charge remains constant, thus giving the model much of its interesting behavior.

Biophysical Phenomena↗
PubMed1986

An animal model of iron overload and its application to study hepatic ferritin iron mobilization by chelators.

Administration of 3,5,5-trimethylhexanoyl ferrocene in the diet of male Wistar rats results in a substantial increase in hepatic ferritin protein (greater than 2-fold) and of ferritin iron (4-8-fold). The iron-loading in liver, under the conditions used, appears to be essentially in parenchymal cells rather than in reticulo-endothelial cells. It is suggested that the model represents a useful system for the study of the potential efficacy of new iron chelators for the mobilization of hepatic storage iron. The ability of desferal (DFO) and of a new siderophore, desferrithiocin (DFT), to mobilize hepatic ferritin iron is observed in this model of iron overload. Desferrithiocin stimulates ferritin iron mobilization, when administered either by gavage or by intraperitoneal injection, whereas desferal is active intraperitoneally but inactive orally. Our studies lead to the conclusion that DFT merits further examinations, for its activity as an orally active iron chelator.

Administration, Oral↗
PubMed2004

Laboratory assessment of the mobility of nanomaterials in porous media.

The production of significant quantities of engineered nanomaterials will inevitably result in the introduction of these materials to the environment. Mobility in a well-defined porous medium was evaluated for eight particulate products of nanochemistry to assess their potential for migration in porous media such as groundwater aquifers and water treatment plant filters. Contrary to the assertion that nanomaterials present monolithic environmental risks, here we show that these nanomaterials exhibit widely differing transport behaviors. Fullerene-based nanomaterials that had been functionalized to facilitate dispersal in water displayed the highest mobilities, with a calculated potential to migrate approximately 10 m in unfractured sand aquifers. Colloidal aggregates of C60, which have been the focus of recent toxicity studies, were among the least mobile of the nanomaterials evaluated.

Colloids↗
PubMedDate not supplied

In vitro microsomal [correction of mircosomal] metabolism of N-benzyl and N-benzoylnornicotine derivates by rat.

The in vitro hepatic microsomal metabolism of N-1'-benzylnornicotine, N-l'-(p-chlorobenzyl)nornicotine, N-1'-benzoylnornicotine and N-1'-(p-chlorobenzoyl) nornicotine was studied using hepatic washed rat microsomal preparations fortified with NADPH. Substrates and their potential metabolites were synthesized, characterised by spectral methods, and separated using a reverse phase HPLC system consisted of a C18 column and a mobile phase composition of acetonitrile: phosphate buffer. Substrates and their potential metabolites were extracted from biological systems with dichloromethane. Metabolites detected were compared with retention times and uv spectra of authentic standards. Metabolic experiments indicated that oxidative dealkylation leading to the formation of nornicotine and the corresponding aldehydes was a major route of metabolism for N-alkylnornicotine substrates. In addition, N-1'-(p-chlorobenzyl)nornicotine produced the corresponding lactam and amide metabolites. N-Acylnornicotines were hydrolysed to nornicotine.

Animals↗
PubMed1995

Effect of interleukin-3 pretreatment on granulocyte/macrophage colony-stimulating factor induced mobilization of circulating haemopoietic progenitor cells.

Recombinant human colony stimulating factors (CSFs) as single agents are increasingly used for mobilizing peripheral blood progenitor cells (PBPCs) for stem cell transplantation. We have shown in rhesus monkeys that interleukin-3 (IL-3) pretreatment markedly potentiated the increase in PBPC numbers of subsequent administration of granulocyte/macrophage-CSF (GM-CSF). Here we studied the effect of IL-3 pretreatment on GM-CSF-induced mobilization of PB progenitors in patients who were potential candidates for autologous stem cell transplantation (n = 16). Patients were treated with GM-CSF at a dose of 5 micrograms/kg/d for 5 d and after a treatment free interval received another cycle of GM-CSF immediately following pretreatment with IL-3 at different doses and duration: 2.5 micrograms/kg/d (n = 4), 5 micrograms/kg/d (n = 3) and 10 micrograms/kg/d (n = 3) for 3 d, 5 micrograms/kg/d for 7 d (n = 4) and 5 micrograms/kg/d for 14 d (n = 2), respectively. Only 7 d pretreatment with IL-3 showed consistent effects. Although IL-3 did not mobilize by itself, pretreatment with 5 micrograms/kg/d of IL-3 for 7 d significantly potentiated GM-CSF-induced mobilization of PB CFU-GM numbers, leading to a mean increase in PB CFU-GM numbers over baseline by 18.5 +/- 5.2 (SEM) fold by IL-3/GM-CSF as compared to a 4.7 +/- 1.7-fold increase by GM-CSF alone. A significant enhancement by the 7 d IL-3 pretreatment was also observed for erythroid (BFU-E) and multipotential progenitor cells (CFU-mix) which were 3.3 +/- 1.3- and 3.4 +/- 0.9-fold, respectively, mobilized by GM-CSF alone, as compared to 8.5 +/- 2.3- and 19.2 +/- 3.4-fold, respectively, by the IL-3/GM-CSF combination. Our results suggest that 7 d pretreatment with IL-3 may be a useful mean to augment mobilization of circulating progenitors by more lineage-restricted CSFs. These findings may be important for the design of mobilization strategies that use growth factors without preceding chemotherapy.

Adolescent↗
PubMed1993

Altered growth and spontaneous transformation of cells cultured from v-jun transgenic mice recapitulate wound-induced multistage tumorigenesis.

H-2K/v-jun transgenic mice develop sarcomas at sites of wounding via a multistep process characterized by discrete pathological stages. To study this progression in vitro, cells from different stages of tumorigenesis were cultured and examined for their growth properties. The results show that whereas transgenic fibroblasts do not manifest enhanced proliferative potential in vivo in the absence of wounding, they do show obvious proliferative advantage relative to nontransgenic fibroblasts in vitro, including the capacity for indefinite growth. In addition, relative to nontransgenic fibroblasts, transgenic cells show altered sensitivity to platelet-derived growth factor and tumor necrosis factor alpha, both of which are known to be mobilized during wounding. No obvious differences in growth potential are observed between transgenic fibroblasts and cells cultured from wound-induced premalignant lesions, and confluent cultures of both cell populations give rise to spontaneous foci of transformed myogenic and nonmyogenic cells that resemble those of late-stage malignant wound sarcomas. Relative to transgenic fibroblast cultures, however, premalignant lesion cultures segregate transformed cells at a greater frequency and after shorter intervals of in vitro growth. The results suggest that wound-induced multistage tumorigenesis can be recapitulated in vitro and that cells cultured from different stages of tumorigenesis retain biological properties that reflect the pathological stage from which they are derived.

Animals↗
PubMed2001

Change of migration time and separation window accompanied by field-enhanced sample stacking in capillary zone electrophoresis.

When field-enhanced sample stacking was used in capillary zone electrophoresis (CZE) analysis of cations, the decrease of migration time and the reduction of separation window was observed with increase of sample plug length. A simple equation expressing the migration velocity in the stacking process was derived to explain the above phenomenon. From experiments and theoretical consideration, we confirmed that this effect was caused by the higher potential gradient and larger eletroosmotic flow (EOF) mobility at the sample plug than those at the supporting electrolyte. A mathematical model appropriate for the computer simulation of such a system was studied considering the experimental results, and it was concluded that electroosmotic velocity (v(eof)) should be introduced to the equation of continuity as a constant.

Cations↗
PubMed2002

Transcriptional control of the human aldehyde dehydrogenase 2 promoter by hepatocyte nuclear factor 4: inhibition by cyclic AMP and COUP transcription factors.

An important regulatory element (designated FP330-3') of the ALDH2 promoter mediates activation by hepatocyte nuclear factor 4 (HNF4). This activation of promoter constructs containing this element by HNF4 was reduced by nearly half by 8-Br-cAMP in H4IIEC3 cells, an effect that was blocked by inhibitors of protein kinase A (PKA). Cotransfection assays showed that COUP-TF I, ARP-1, or PPARdelta suppressed the ability of HNF4 to activate the reporter. The repression was potentiated by 8-Br-cAMP. Electrophoretic mobility shift assays revealed that treatment of hepatoma cells or cultured rat hepatocytes with 1 mM 8-Br-cAMP or glucagon reduced binding of FP330-3' by HNF4 by half. In vitro phosphorylation of HNF4 by PKA decreased binding to FP330-3'. Fasting reduced the ALDH2 protein level in liver and kidney, two tissues expressing HNF4, but not heart. These data suggest that ALDH2 expression can be suppressed by cAMP, most likely through phosphorylation of HNF4 by PKA, and this may account for the reduction in enzyme protein during fasting.

Aldehyde Dehydrogenase↗
PubMed1997

Evaluation of a potential regulatory role for inverted CCAAT boxes in the human topoisomerase II alpha promoter.

Several chemotherapeutic agents act via inhibition of topoisomerase (topo) II activity. Topo II levels appear to correlate with drug sensitivity in vivo. The DNA immediately 5' to the topo II alpha coding region contains five potentially regulatory inverted CCAAT boxes (ICB). Electrophoretic mobility shift assays (EMSA) using oligomers containing the wild type forms of these ICBs show specific DNA-protein binding. Mutations in these ICBs result in loss of protein binding. EMSA competition studies indicate that the four most 3' ICBs (1-4) bind to the same protein(s), while the most 5' ICB (5) binds to a different protein(s). EMSA supershift assays with antibodies to two known CCAAT binding proteins, CBF and CEB/P, indicate that ICBs 1-4 are binding to CBF, but ICB 5 is not bound by either of these proteins.

Antigens, Neoplasm↗
PubMed1999

The cassettes and 3' conserved segment of an integron from Klebsiella oxytoca plasmid pACM1.

pACM1 is a conjugative multiresistance plasmid from Klebsiella oxytoca that encodes SHV-5 extended-spectrum beta-lactamase (ESBL) and has two integrons. The first is a type I (sul type); the second, detected by hybridization with an intI gene probe, has been putatively identified as a defective type I integron. The cassette region of the first integron has now been fully sequenced and contains three aminoglycoside resistance determinants (aac(6')-Ib, aac(3)-Ia, and ant(3")-Ia) and two open reading frames of unknown function. In addition, sequencing of a region downstream from the qacEDelta1-sulI-ORF 5 gene cluster of the first integron revealed a copy of insertion sequence IS6100 flanked by inverted copies of sequence from the 11.2-kb insert (In2) of Tn21. This arrangement is similar to that found in In4 of Tn1696. The coincidence of an ESBL gene and mobile elements on a conjugative plasmid has potential implications for the spread of ESBL-mediated drug resistance, though evidence of bla((SHV-5)) movement mediated by these elements has not been found.

Amino Acid Sequence↗
PubMed2006

Seasonal regulations of energetics, serum concentrations of leptin, and uncoupling protein 1 content of brown adipose tissue in root voles (Microtus oeconomus) from the Qinghai-Tibetan plateau.

Survival of small mammals in winter requires proper adjustments in physiology, behavior and morphology. The present study was designed to examine the changes in serum leptin concentration and the molecular basis of thermogenesis in seasonally acclimatized root voles (Microtus oeconomus) from the Qinghai-Tibetan plateau. In January root voles had lower body mass and body fat mass coupled with higher nonshivering thermogenesis (NST) capacity. Consistently, cytochrome c oxidase activity and mitochondrial uncoupling protein-1 (UCP1) protein contents in brown adipose tissues were higher in January as compared to that in July. Circulating level of serum leptin was significantly lower in winter and higher in July. Correlation analysis showed that serum leptin levels were positively related with body mass and body fat mass while negatively correlated with UCP1 protein contents. Together, these data provided further evidence for our previous findings that root voles from the Qinghai-Tibetan plateau mainly depend on higher NST coupled with lower body mass to enhance winter survival. Further, fat deposition was significantly mobilized in cold winter and leptin was potentially involved in the regulation of body mass and thermogenesis in root voles. Serum leptin might act as a starvation signal in winter and satiety signal in summer.

Adipose Tissue, Brown↗
PubMed2006

Management of blunt tracheal trauma in children: a case series and review of the literature.

Blunt tracheal trauma seldom develops in children because of their anatomy and the mobility of the cartilage. It has the potential to be overlooked, either because of the severity of concomitant injuries or because of the unfamiliarity of paediatricians with this type of injury. However, tracheal injury might be lethal due to airway compromise. Early bronchoscopy may be necessary to anticipate complications and prevent permanent dysfunction. We present a retrospective, double-institution case series over a 5-year period, describing five children, aged 3 to 14 years, with tracheal injury after blunt cervical trauma. All patients showed emphysema with pneumomediastinum. After explorative bronchoscopy, all patients were successfully treated with antibiotics and/or supportive ventilation. In summary, minimal lesions due to blunt tracheal trauma could be treated conservatively in children. Since the external signs of tracheal injury are not indicative of the extent of the trauma, a high index of suspicion is warranted in these patients.

Adolescent↗
PubMed1993

Nonsteroidal antiinflammatory drugs and reproduction.

The role of nonsteroidal antiinflammatory drugs in human reproduction and reproductive disorders is reviewed. Nonsteroidal antiinflammatory drugs inhibit the biosynthesis of prostanoids and can cross the placental barrier into the fetal circulation. Nonsteroidal antiinflammatory drugs are the treatment of choice in primary dysmenorrhea and intrauterine contraceptive device-induced dysmenorrhea and menorrhagia. Nonsteroidal antiinflammatory drugs can be used for effective control of menorrhagia, preterm labor, and polyhydramnios and for prevention of preeclampsia, but larger definitive clinical trials are needed. Prostaglandin inhibition with some nonsteroidal antiinflammatory drugs appear promising in the relief of some premenstrual symptoms and in the prevention of postoperative pelvic adhesion formation, but more studies are needed in women. Whereas implantation and tubal mobility are mediated by local prostaglandins, the potential use of nonsteroidal antiinflammatory drugs to suppress prostaglandin in these reproductive processes for enhancing or reducing fertility warrants further studies. In the last 2 decades nonsteroidal antiinflammatory drugs have been used increasingly in the treatment of some reproductive disorders and are promising for many others.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

Multiple trauma and the burn patient.

Multiple trauma greatly complicates the care of the burn patient, whereas a burn often complicates the diagnosis and treatment of the trauma patient. One hundred seventy-six of 3,550 consecutive acute burn admissions received nonburn trauma. The majority of injuries were sustained in motor vehicle accidents (70), escaping fire (32), electrical burns with falls (24), scald burns associated with assault (22), and explosions (18). Eighty patients received orthopedic injuries, including major (47), minor (25), and multiple (28) fractures, 10 dislocations, and 4 open joints. Soft-tissue injury occurred in 91 patients, head injury in 30, thoracic trauma in 27, and abdominal injury in 15. Unstable orthopedic injuries were major contributors to morbidity. Early internal and external fixation permitted optimal mobilization and wound care. Awareness of the potential for multiple injuries and the team approach to these injuries are the most important factors in appropriate care.

Adolescent↗