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At least 793 records · Page 44Linked to original sources
PubMed1991

The failure of skin grafting to break tolerance to class I-disparate renal allografts in miniature swine despite inducing marked antidonor cellular immunity.

Long-term specific tolerance to one haplotype class I plus minor antigen disparate renal allografts develops without exogenous immunosuppression in approximately 35% of miniature swine (n = 128). Previous studies have suggested that this phenomenon is related to limited class I-specific helper T cell activity as evidenced by the failure of antibody class switching in vivo and the ability of exogenous interleukin 2 to elicit antidonor responses in vitro. To determine whether tolerance could be broken by inducing antidonor reactivity with donor antigen and a source of T cell help, multiple skin grafts bearing donor class I plus third-party class II antigens were placed on tolerant animals. Skin grafts were placed at least 3 months after the kidney transplant, at which time all recipients had normal renal function as measured by blood urea nitrogen and serum creatinine. First-set rejection of skin grafts by SLAad and SLAdd hosts occurred in 11.8 +/- 1.1 days (mean +/- SEM, n = 6) and in 9.3 +/- 0.9 days (n = 4), respectively. Coincident with skin rejection, most animals developed a transient rise in BUN to 62 +/- 11 mg/dl (n = 10) and a similar rise in Cr to 4.9 +/- 1.2 mg/dl (n = 10), with normal levels returning in all animals within two weeks. Subsequent skin grafts with the same disparity did not undergo second-set rejection and did not induce BUN or Cr elevations. Prior to skin grafting, animals showed no antidonor activity in mixed lymphocyte reaction or cell-mediated lymphocytotoxicity assays. After two skin grafts, all animals developed donor-specific CML and secondary MLR responses, and additional skin grafts amplified this cellular immunity. Development of marked antidonor immunity without a break in tolerance suggested that either graft adaptation or local suppression might be involved in maintaining tolerance to class I MHC antigens. In preliminary studies, an immunized SLAad animal and an immunized SLAdd animal were retransplanted with kidneys MHC matched to their first allografts. In both cases, the second graft was accepted permanently without immunosuppression, suggesting that graft adaptation is not necessary for the maintenance of tolerance to renal allografts in miniature swine.

Animals↗
PubMedDate not supplied

Rapid adaptation to auditory-visual spatial disparity.

The so-called ventriloquism aftereffect is a remarkable example of rapid adaptative changes in spatial localization caused by visual stimuli. After exposure to a consistent spatial disparity of auditory and visual stimuli, localization of sound sources is systematically shifted to correct for the deviation of the sound from visual positions during the previous adaptation period. In the present study, this aftereffect was induced by presenting, within 17 min, 1800 repetitive noise or pure-tone bursts in combination with synchronized, and 20 degrees disparate flashing light spots, in total darkness. Post-adaptive sound localization, measured by a method of manual pointing, was significantly shifted 2.4 degrees (noise), 3.1 degrees (1 kHz tones), or 5.8 degrees (4 kHz tones) compared with the pre-adaptation condition. There was no transfer across frequencies; that is, shifts in localization were insignificant when the frequencies used for adaptation and the post-adaptation localization test were different. It is hypothesized that these aftereffects may rely on shifts in neural representations of auditory space with respect to those of visual space, induced by intersensory spatial disparity, and may thus reflect a phenomenon of neural short-term plasticity.

Acoustic Stimulation↗
PubMed2025

Sex-Biased Admixture Followed by Isolation and Adaptive Evolution Shaped the Genomic and Blood Pressure Diversity of the LopNur People.

The LopNur people are an ethnic group living on the edge of the Taklamakan Desert, and they are believed to demonstrate a unique genetic makeup due to their isolation and limited contact with neighboring populations. However, a lack of genetic studies on the LopNur people has resulted in limited knowledge about their ancestral origins and demographic history. Here, we conducted the first whole-genome sequencing study of 164 LopNur individuals (LOP) to gain insight into their genetic history and adaptive evolution in an isolated desert area. Our analysis revealed that the present-day LOP have experienced a complex history of admixture followed by long-term isolation, with their ancestry derived from East Asia (∼41.46%), West Eurasia (∼26.43%), Siberia (∼24.27%), and South Asia (∼7.82%). Notably, a remarkable sex-biased admixture occurred between Western males and Eastern females. In addition to complex admixture followed by long-term geographic isolation and further recent migrations, adaptive evolution jointly formed the gene pool and phenotypic diversity of the present-day LOP. Intriguingly, our analysis suggests that the USP35-GAB2 region may be correlated with blood pressure in LOP, based on a joint analysis of genomics and blood pressure data. Moreover, we identified two variants, rs7387065, and rs2229437, located on CSMD1 and PRCP, respectively. These variants exhibited frequency differences between Asian and European populations and were reported to be associated with antihypertensive drug absorption. Our results provide new insight into the complex history of the LOP, an admixed and isolated ethnic group residing at the crossroads of East and West, a case with ancient admixture, long-term isolation, adaptive evolution, and sex-biased gene flow.

Female↗
PubMed1998

Development of a pediatric liver transplantation program in Argentina.

This article describes the preliminary experimental steps and clinical implementation of a purely pediatric liver transplantation (LT) program in a large public children's hospital in Buenos Aires, Argentina, a city with well over 10 million inhabitants and a referral population of over 30 million. Between 1993 and 1997, 84 LTs were performed in 81 patients, of which one-fourth weighed below 10 kg. The main indications were biliary atresia (n = 25, 30%) and fulminant liver failure (n = 23, 27%), followed by autoimmune cirrhosis (n = 14, 16%) and other liver diseases. Shortage of organs due to local conditions led to the use of liver-reduction techniques in 48 cases (57%), split liver in 2, and living-related donor (LRD) in 2. Retransplantation was necessary in 3 instances. Seventy-eight percent of the recipients survived for more than 1 year and 71% were alive after 4 years. The authors comment on the need for adaptation to local conditioning factors when developing a pediatric LT program in any country in which demographics and economic, medical, and sociological environments have a decisive influence on organ procurement, the actual performance of the operation, and the lifelong postoperative medication. In Buenos Aires, where the hospital setting is well-developed, the indications are in part determined by the high incidence of hepatitis A. Organ shortages in our area led to liberal use of liver reduction, split-liver, and LRD techniques. The overall results of the first years of such a program were largely satisfactory.

Argentina↗
PubMed1997

Glucose metabolism in pig outer retina in light and darkness.

Glucose metabolism in the outer retina of pigs was studied in the light and in the dark in pentobarbital anaesthetized pigs. Blood was collected from a vortex vein and an artery, and the arteriovenous concentration differences of lactate, glucose and oxygen were determined in light-adapted eyes. Local blood flows were simultaneously determined using the microsphere method. In a second group of experiments, the flow from a vortex vein and arteriovenous concentration differences were measured in both darkness and light. In light, the mean net lactate formation and oxygen and glucose consumption in the outer retina were about 0.137, 0.150 and0.115 mumol min-1, respectively. In eyes previously dark-adapted, constant light caused a 63% reduction in lactate formation, whilst oxygen and glucose consumptions were reduced by 40 and 44%, respectively. The results indicate that in both darkness and constant light, most of the glucose consumed by the outer retina is used in lactate formation, and that less than 20% is oxidized. Energy production through glycolysis and glucose oxidation is approx. 42% lower in constant light than in darkness.

Adaptation, Ocular↗
PubMedDate not supplied

A cross-site qualitative study of physician order entry.

OBJECTIVE: To describe the perceptions of diverse professionals involved in computerized physician order entry (POE) at sites where POE has been successfully implemented and to identify differences between teaching and nonteaching hospitals. DESIGN: A multidisciplinary team used observation, focus groups, and interviews with clinical, administrative, and information technology staff to gather data at three sites. Field notes and transcripts were coded using an inductive approach to identify patterns and themes in the data. MEASUREMENTS: Patterns and themes concerning perceptions of POE were identified. RESULTS: Four high-level themes were identified: (1) organizational issues such as collaboration, pride, culture, power, politics, and control; (2) clinical and professional issues involving adaptation to local practices, preferences, and policies; (3) technical/implementation issues, including usability, time, training and support; and (4) issues related to the organization of information and knowledge, such as system rigidity and integration. Relevant differences between teaching and nonteaching hospitals include extent of collaboration, staff longevity, and organizational missions. CONCLUSION: An organizational culture characterized by collaboration and trust and an ongoing process that includes active clinician engagement in adaptation of the technology were important elements in successful implementation of physician order entry at the institutions that we studied.

Attitude of Health Personnel↗
PubMed2006

Methodologic challenges in disseminating evidence-based interventions to promote physical activity.

During the past decade, numerous intervention studies have been published on the effectiveness of programs to promote active living; however, few studies have addressed the dissemination of effective physical activity interventions. Both community settings and healthcare settings are important locations for dissemination of evidence-based programs and policies. A major gap in the existing literature involves the appropriate methodologic approaches for planning, evaluating, and reporting on dissemination efforts for effective and promising interventions in these locations. To address this gap, two hypothetical dissemination studies are presented: a quasi-experimental study of local health agencies (Scenario 1) and a group-randomized trial of clinical practices (Scenario 2). These studies help to elucidate the barriers and opportunities for implementing evidence-based physical activity interventions across different settings. Based on the scenarios, the existing literature, and the authors' experience, dissemination challenges that researchers and practitioners may experience (i.e., issues of design, measures of outcomes and external validity, the balance between fidelity and adaptation to local settings, and the review and funding of dissemination science) are discussed. Researchers, practitioners, and policymakers are invited to address the issues outlined in this article in order to bridge the gap between the generation of new knowledge on efficacious physical activity interventions and widespread application of these approaches in community and clinical settings.

Community Health Services↗
PubMed2000

Experimental evidence for the adaptive evolution of growth rate in the garter snake Thamnophis elegans.

The western terrestrial garter snake (Thamnophis elegans) varies significantly in individual growth rates and life-history traits (maturation, reproduction, and survival) among adjacent populations in nature. This study focuses on assessing the genetic and environmental components of the substantial among-population variation in growth rates. Litters of neonates from nine populations inhabiting either mountain meadow or lakeshore habitat were reared for one year in a common-garden experiment with two temperature treatments. Diet, frequency of feeding, light exposure, and daytime temperatures were identical for all individuals. The two different nighttime temperatures (20 degrees C and 25 degrees C) were chosen to mirror field differences in nighttime thermoregulatory constraints for mountain-meadow and lakeshore snakes, respectively. Temperature and source habitat interacted to affect first-year growth rate. Neonates from meadow dams grew fastest in the cooler treatment, whereas those from lakeshore dams grew fastest in the warmer treatment. The observation that naive neonates, which were gestated and raised under identical conditions, grew fastest in environments characteristic of their natal population is evidence both that there are genetic differences among populations for growth and that these differences reflect adaptation to local habitats at a very small geographic scale. In addition, significant directional selection for large birthweight was measured for neonates from all populations. These results are considered in the context of population colonization history, migration and selection, and competing models for growth rate variation.

Adaptation, Physiological↗
PubMed2005

Activity, substrate detection and immunolocalization of glutathione peroxidase (GPx) in bovine reproductive organs and semen.

The purpose of the current study was to further investigate the role of the antioxidant selenium-dependent enzyme glutathione peroxidase (GPx) in reproductive organs and semen from bulls. To this end a fast and convenient combined method for immune detection and substrate localization was adapted, which allows the assessment of both molecular weight and peroxidase activity of proteins on one and the same SDS-PAGE gel plate. After routine semen analysis of ejaculates, a spectrophotometrical assay of GPx activity in bovine semen was performed. For the immunological analyses performed, a rabbit polyclonal monospecific antibody against GPx was raised. Substrate detection and immunolocalization of GPx in lysates from bovine testis, epididymis, spermatozoa, and seminal plasma was performed. In order to determine the localization of GPx in spermatozoa, immunofluorescence analysis was performed. A positive correlation was established between GPx activity in semen and the number of motile spermatozoa. A negative correlation was observed between GPx activity and the number of immotile spermatozoa. The combined method for immunodetection and substrate localization was tested and proved reliable. Both tetramer and monomer forms of GPx were detected in lysates from testis, epididymis, and spermatozoa. We found no GPx activity in seminal plasma. Immunofluorescence shows the presence of GPx chiefly in the mitochondrial and in the acrosome regions of spermatozoa. GPx activity remained stable under the extreme experimental conditions.

Animals↗
PubMed2003

A model of physical factors in the structural adaptation of microvascular networks in normotension and hypertension.

Adequate function of the microcirculation is vital to any tissue. To maintain an optimal function, microvascular networks must be able to adapt structurally to changes in the physical environment. Here we present a mathematical network model based on vessel wall mechanics. We assume based on experimental observations that longstanding change in transmural pressure elicits a change in the vascular wall-to-lumen ratio for maintaining circumferential wall stress at a certain level. In addition, experimental observations show that chronic change in fluid shear stress at the vascular wall elicits a persistent change in luminal diameter. On this basis we hypothesize that wall influencing substances released from the endothelium in response to shear stress have a certain optimal level in the vascular wall. Deviation from this level will cause vascular remodeling, i.e. a structural change in luminal diameter, until equilibrium is restored. The model explains several of the key features observed experimentally in the microcirculation in normotension and hypertension. Most importantly, it suggests a scenario where overall network structure and network hemodynamics depend on adaptation to local hemodynamic stimuli in the individual vessel. Simulated results show emanating microvascular networks with properties similar to those observed in vivo. The model points to an altered endothelial function as a key factor in the development of vascular changes characteristic of hypertension.

Adaptation, Physiological↗
PubMedDate not supplied

[A comparative ultrastructural and morphometric analysis of the smooth myocytes in the tunicae intima and media of the human fetal aorta].

Transmission electron microscopy was used for studying the thoracic part of the aorta of 9 human fetuses of 20-28 weeks of development. In the medial tunic of the human fetus aorta there are smooth myocytes (SM) of the contractile and synthetic phenotypes. The latter are localized mainly in the inner part of the media. In the inner tunic there are also SM of the synthetic phenotype. With the help of processes they make contacts with endotheliocytes and processes of SM of the media. In the gaps between the subendothelial SM and endothelium there are particles of elastin which form the structure resembling an additional elastic membrane. It is reasonable to think that the migration of SM into the intima is a stage of normal development of the vessel associated with the adaptation to local hemodynamic conditions rather than an initial manifestation of atherosclerosis.

Aorta, Thoracic↗
PubMedDate not supplied

Strengthening local health care management in Bolivian districts through participatory operational research.

The purpose of this article is to demonstrate how the use of a participatory health care management and problem-related research methodology may help strengthen health service management and the capacities of local health care personnel. The text refers to five studies carried out in three Bolivian health districts from 1993-1995, in an Operational Research Project, conducted by an Italian N.G.O. (Cooperazione Internazionale) in agreement with the local Ministry of Health and P.A.H.O./W.H.O. The object of these studies was to assess the main problems in health care delivery and to define and implement appropriate solutions. The studies utilized a methodology based on the principles of operational research and continuous quality improvement. During the process some positive aspects and difficulties were met. The positive aspects were: the applied character of the research focused on the solution of a problem; the study of a problem related to health service management; the use of modern and simple techniques adapted to local knowledge; on-the-job training of health care personnel during the research process. Lack of a generic 'culture of research' and poor health personnel training were the main difficulties encountered. National health authorities should take these points into account to define or readjust policies on health service research, health workers' academic education and in-service training. Insisting on developing human resources and allowing them to achieve and expand their potential is the key factor for getting developing countries out of their current crisis and toward reaching a truly human and sustainable development.

Bolivia↗
PubMedDate not supplied

[Vector control and malaria control].

Vector control is an integral part of malaria control. Limiting parasite transmission vector control must be considered as one of the main preventive measure. Indeed it prevents transmission of Plasmodium from man to vector and from vector to man. But vector control must be adapted to local situation to be efficient and feasible. Targets of vector control can be larval and/or adults stages. In both cases 3 main methods are currently available: physical (source reduction), chemical (insecticides) and biological tolls. Antilarval control is useful only in some particular circumstances (unstable malaria, island, oasis...) Antiadult control is mainly based upon house-spraying while pyrethroid treated bed nets is advocated regarding efficiency, simple technique and cheap price. Vector control measures could seem restricted but can be very efficient if political will is added to a right choice of adapted measures, a good training of involved personal and a large information of the population concerned with vector control.

Africa↗
PubMed1995

Adaptations of rat lateral gastrocnemius motor units in response to voluntary running.

This study investigated the effects of 12 wk of voluntary wheel running on motor units from rat lateral gastrocnemius. Motor units were isolated via ventral root splitting (L5) from active or sedentary rats and were classified into slow, fast-fatigue-resistant, and fast-fatigable (FF) units. An overall increase in mean motor unit tetanic tension (35%) was accompanied by a decrease in mean motor unit fatigue resistance (-10%). These adaptations were localized in the fast unit population but varied among fast motor unit subtypes. The overall increase in tetanic force was due primarily to increases in fast-fatigue-resistant units (300%), whereas changes in fatigue resistance (-43%) were confined to FF units. However, the changes seen with activity may have been partly obscured by classifying fast motor units based on fatigability, since a significant increase in tetanic force accompanied by a decreased twitch one-half relaxation time was apparent in units falling in the midrange of the tetanic force continuum and included a number of FF units. These data provide direct demonstration of nonuniform motor unit adaptations subsequent to increases in normal functional activity.

Animals↗
PubMedDate not supplied

[The recycling of waste water and mosquitoes].

Recycling waste water in the Achères complex (North-West Paris) is based on both sophisticated industrial techniques and simple agricultural methods. The sewage farms and settling pools provide suitable breeding sites for more than ten mosquito species. Aedes caspius is the major pest for the local population. Moreover Culex pipiens (anthropophilic form) breeds in the sewers of the neighbouring towns. Mosquito control is based early ground treatment of breeding sites. Temephos and fenotrothion are used against A. caspius. Spherimos (Bacillus sphaericus) is used to control C. pipiens. The two insecticides have no adverse effect on humans or the environment and Spherimos is harmless. Aedes pest have been virtually eliminated. Urban Culex control is generally good despite being performed by less well trained municipal employees. In the areas treated by the specialized team of the SIAAP, pest mosquitoes have disappeared. The techniques used in the Achères complex do not require sophisticated equipment. Thus, if adapted to local ecological, epidemiological and financial conditions they could be transferred to developing countries.

Aedes↗
PubMed2005

Hyperosmotic stimulus induces reversible angiogenesis within the hypothalamic magnocellular nuclei of the adult rat: a potential role for neuronal vascular endothelial growth factor.

BACKGROUND: In mammals, the CNS vasculature is established during the postnatal period via active angiogenesis, providing different brain regions with capillary networks of various densities that locally supply adapted metabolic support to neurons. Thereafter this vasculature remains essentially quiescent excepted for specific pathologies. In the adult rat hypothalamus, a particularly dense network of capillary vessels is associated with the supraoptic (SON) and paraventricular (PVN) nuclei containing the magnocellular neurons secreting vasopressin and oxytocin, two neurohormones involved in the control of the body fluid homoeostasis. In the seventies, it was reported that proliferation of astrocytes and endothelial cells occurs within these hypothalamic nuclei when strong metabolic activation of the vasopressinergic and oxytocinergic neurons was induced by prolonged hyperosmotic stimulation. The aim of the present study was to determine whether such proliferative response to osmotic stimulus is related to local angiogenesis and to elucidate the cellular and molecular mechanisms involved. RESULTS: Our results provide evidence that cell proliferation occurring within the SON of osmotically stimulated adult rats corresponds to local angiogenesis. We show that 1) a large majority of the SON proliferative cells is associated with capillary vessels, 2) this proliferative response correlates with a progressive increase in density of the capillary network within the nucleus, and 3) SON capillary vessels exhibit an increased expression of nestin and vimentin, two markers of newly formed vessels. Contrasting with most adult CNS neurons, hypothalamic magnocellular neurons were found to express vascular endothelial growth factor (VEGF), a potent angiogenic factor whose production was increased by osmotic stimulus. When VEGF was inhibited by dexamethasone treatment or by the local application of a blocking antibody, the angiogenic response was strongly inhibited within the hypothalamic magnocellular nuclei of hyperosmotically stimulated rats. CONCLUSION: This study shows that the functional stimulation of hypothalamic magnocellular neurons of adult rats induces reversible angiogenesis via the local secretion of neuronal VEGF. Since many diseases are driven by unregulated angiogenesis, the hypothalamic magnocellular nuclei should provide an interesting model to study the cellular and molecular mechanisms involved in the regulation of angiogenesis processes within the adult CNS.

Animals↗
PubMedDate not supplied

Field research in humanitarian medical programmes. Treatment of a cohort of tuberculosis patients using the Manyatta regimen in a conflict zone in South Sudan.

This is a descriptive report of a pilot project of tuberculosis (TB) treatment in a conflict zone. A TB programme was implemented by Médecins Sans Frontières(MSF)-Holland in a semi-nomadic population in a very insecure and underdeveloped area of Upper Nile province in Southern Sudan. Outcome measures were operational feasibility, default rate, and sputum smear conversion at 4 months. A cohort of TB patients was admitted over a 10-week period (July-September 2001). Adherence strategy, project implementation, and and contingency planning were adapted to local conditions. The treatment regimen (4 HRZE [4-month daily supervised regimen] followed by 3EH or 3TH [3-month unsupervised regimen]: isoniazid (H), rifampicin (R), pyrazinamide (Z), ethambutol (E) and thiacetazone (T)) was a variant on the Manyatta regimen developed for semi-nomads in Kenya. Of 163 patients, 84 (52%) were children aged < 15 years. Lymph node TB comprised 34% and spinal TB 15% of all patients. Among adults, 41% had smear-positive pulmonary disease. Only 1 patient (0.6%) defaulted. All sputum smear-positive patients who completed 4 months of therapy converted to smear-negative, although 2 were subsequently found to have relapsed. TB in complex emergency situations is an underrecognized priority. Using an approach adapted especially to this setting, TB treatment was successfully implemented with minimal risk of promoting drug resistance, in an unstable setting.

Adolescent↗
PubMed1995

A model of excitation and adaptation in bacterial chemotaxis.

We present a model of the chemotactic mechanism of Escherichia coli that exhibits both initial excitation and eventual complete adaptation to any and all levels of stimulus ("exact" adaptation). In setting up the reaction network, we use only known interactions and experimentally determined cytosolic concentrations. Whenever possible, rate coefficients are first assigned experimentally measured values; second, we permit some variation in these rate coefficients by using a multiple-well optimization technique and incremental adjustment to obtain values that are sufficient to engender initial response to stimuli (excitation) and an eventual return of behavior to baseline (adaptation). The predictions of the model are similar to the observed behavior of wild-type bacteria in regard to the time scale of excitation in the presence of both attractant and repellent. The model predicts a weaker response to attractant than that observed experimentally, and the time scale of adaptation does not depend as strongly upon stimulant concentration as does that for wild-type bacteria. The mechanism responsible for long-term adaptation is local rather than global: on addition of a repellent or attractant, the receptor types not sensitive to that attractant or repellent do not change their average methylation level in the long term, although transient changes do occur. By carrying out a phenomenological simulation of bacterial chemotaxis, we find that the model is insufficiently sensitive to effect taxis in a gradient of attractant. However, by arbitrarily increasing the sensitivity of the motor to the tumble effector (phosphorylated CheY), we can obtain chemotactic behavior.

Adaptation, Biological↗