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At least 883 records · Page 49Linked to original sources
PubMed2003

RNAi as a gene therapy approach.

RNA duplexes of 21 - 23 nucleotides (nts), with approximately 2 nt 3' overhangs (called small interfering RNAs or siRNAs), have recently been shown to mediate sequence-specific inhibition of gene expression in mammalian cells via a post-transcriptional gene silencing (PTGS) mechanism termed RNA interference (RNAi). RNAi has been rapidly adopted as a functional genomics tool in a wide range of species, has been adapted to allow for the transient or stable knockdown of gene expression generation in cell lines and animals, and has been developed for high-throughput analysis of gene function in Caenorhabditis elegans. With an increasing list of genes successfully knocked-down by RNAi in mammalian cells and improvements in the delivery of siRNAs to cells, including in vivo delivery to mice, attention is now turning to assessing the potential RNAi has as a gene therapy approach. RNAi is likely to have the greatest impact as a therapeutic tool in two key clinical areas, cancer and infectious disease, but it also has the potential as a therapy for other disorders including some dominant genetic diseases. This review will describe the status of the science behind this novel mechanism and will illustrate the therapeutic potential of RNAi-based technologies, using examples from these critical clinical research areas.

Animals↗
PubMed2001

Fetal endocrinology and development--manipulation and adaptation to long-term nutritional and environmental challenges.

This article reviews the fetal endocrine system in sheep, a species that has a long gestation and primarily produces a singleton fetus. Attention is focused on information that is applicable to humans. The endocrinology of metabolic homeostasis in sheep fetuses is well adapted to respond to a range of metabolic challenges, including placental restriction and maternal undernutrition. A small placenta results in hypoxaemia, hypoglycaemia, reduced abundance of anabolic hormones, and fetal growth restriction. Fetuses with restricted growth are characterized by tissue-specific reductions in hormone receptor mRNA, for example mRNA for the long form of prolactin receptor is reduced in adipose tissue. In contrast, the adipose tissue of fetuses with accelerated growth, stimulated by increasing maternal nutrition in the second half of gestation, has more protein for the long form of the prolactin receptor and more uncoupling protein 1, by which large amounts of heat are generated at birth. Maternal undernutrition in early gestation, coinciding with the period of rapid placental growth, initially restricts placental growth, but when mothers are fed to requirements, a longer fetus results with a disproportionately large placenta. This nutritional manipulation replicates, in part, epidemiological findings from the Dutch famine of 1944-1945, for which the offspring are at increased risk of adult obesity.

Animal Nutritional Physiological Phenomena↗
PubMed2002

Behavioural significance of prolactin signalling in the central nervous system during pregnancy and lactation.

The role of prolactin in the regulation of mammary gland development and function during pregnancy and lactation is well established. However, in addition, prolactin appears to have a much wider role in the physiology of lactation. There is widespread expression of prolactin receptors in the hypothalamus during lactation, indicative of a multi-faceted role for prolactin in regulating hypothalamic function. During pregnancy and lactation, the maternal brain undergoes structural and functional modification, allowing the establishment of appropriate behaviour to feed and nurture the offspring, to adjust to the nutritional and metabolic demands of milk production, and to maintain appropriate hormone secretion to allow milk synthesis, secretion and ejection. The coordination of such a range of neurobiological and neuroendocrine adaptations requires an endocrine signalling mechanism, capable of communicating the reproductive state to the brain. Evidence indicates that prolactin is part of this mechanism.

Animals↗
PubMed2006

Differential temperature acclimatization responses in the membrane phospholipids of Posthodiplostomum minimum and its second intermediate host, Lepomis macrochirus.

The effects of temperature change on phospholipid content in metacercariae of Posthodiplostomum minimum and their second intermediate hosts, Lepomis macrochirus, were examined to gauge similarities in the homeoviscous adaptation of host and parasite membranes to environmental thermal change. Heart, liver, and muscle tissues from individual L. macrochirus responded to environmental temperature declines with a decrease in the ratio of phosphatidylethanolamine (PE) to phosphatidylcholine (PC). Increases in membrane PE concentration increase membrane fluidity, maintaining fish membrane function as environmental temperature declines. However, the metacercariae of P. minimum exhibit changes in cholesterol levels, total lipid levels, and lipid composition (PE/PC) that contrast the normal changes for homeoviscous membrane adaptation exhibited by their fish intermediate hosts. The parasites seem to rely on their hosts for homeoviscous adaptation within normal developmental temperature ranges, pooling both cholesterol and PE as energetic stores for development and ontological transitions signaled by elevated temperatures.

Acclimatization↗
PubMedDate not supplied

A continuous glucose monitoring system based on microdialysis.

The development of a system for continuous glucose measurement is described. A microdialysis fibre is used to continuously withdraw the glucose sample. After passing through the microdialysis fibre the perfusion liquid enters a micro-enzyme reactor which is filled with immobilized glucose oxidase. The enzyme activity, which varies with the glucose concentration, is monitored by an oxygen electrode. The measuring system can be adapted to a desired dynamic range by varying the perfusion rate. The measurement system has been calibrated for two different perfusion rates and shows a linear response to glucose concentrations between 0-3.5 mmol at 12 microliters/min and 0-8 mmol at 25 microliters/min. A probe, which can be configured with different lengths of the dialysing fibre, has also been designed to enable subcutaneous insertion of the microdialysis fibre in clinical studies. Subcutaneous glucose sampling by means of microdialysis is suggested to be used in the design of a glucose monitoring device for clinical use.

Blood Glucose↗
PubMedDate not supplied

Integration in the ventral medulla and coordination of sympathetic, pain and arousal functions.

The nucleus paragigantocellularis lateralis (PGi) in the rostral ventral medulla is implicated in several functions including cardiovascular control, respiration, pain and analgesia. More recent studies implicate this region in alertness and attention as well, by virtue of its prominent projections to the nucleus locus coeruleus (LC). To investigate information that is integrated in the PGi, we used tract tracing to examine brain and spinal projections to this region. Afferents to PGi were found to be functionally diverse and topographically organized. Projections to the retrofacial PGi are primarily autonomic in nature. A wider range of inputs were found to target the rostral (juxtafacial) aspect of the PGi, including brain nuclei involved in the processing of somatosensory and auditory stimuli, as well as autonomic areas. Efferent projections to the LC were also examined in detail. Neuropharmacology experiments revealed that the PGi provides a potent excitatory amino acid input to the LC and an inhibitory input acting at alpha 2 receptors on LC neurons. PGi neurons projecting to the LC stained for markers of adrenaline, enkephalin, GABA and corticotropin releasing factor. Finally, some PGi neurons collateralize to innervate both the LC and the spinal cord. These results suggest that the LC may function in parallel to peripheral autonomic systems providing a cognitive complement to sympathetic function, and that the PGi may integrate a wide range of inputs to facilitate adaptive responses to urgent environmental events.

Afferent Pathways↗
PubMed1995

Light and dark adaptation of visually perceived eye level controlled by visual pitch.

The pitch of a visual field systematically influences the elevation at which a monocularly viewing subject sets a target so as to appear at visually perceived eye level (VPEL). The deviation of the setting from true eye level average approximately 0.6 times the angle of pitch while viewing a fully illuminated complexly structured visual field and is only slightly less with one or two pitched-from-vertical lines in a dark field (Matin & Li, 1994a). The deviation of VPEL from baseline following 20 min of dark adaptation reaches its full value less than 1 min after the onset of illumination of the pitched visual field and decays exponentially in darkness following 5 min of exposure to visual pitch, either 30 degrees topbackward or 20 degrees topforward. The magnitude of the VPEL deviation measured with the dark-adapted right eye following left-eye exposure to pitch was 85% of the deviation that followed pitch exposure of the right eye itself. Time constants for VPEL decay to the dark baseline were the same for same-eye and cross-adaptation conditions and averaged about 4 min. The time constants for decay during dark adaptation were somewhat smaller, and the change during dark adaptation extended over a 16% smaller range following the viewing of the dim two-line pitched-from-vertical stimulus than following the viewing of the complex field. The temporal course of light and dark adaptation of VPEL is virtually identical to the course of light and dark adaptation of the scotopic luminance threshold following exposure to the same luminance. We suggest that, following rod stimulation along particular retinal orientations by portions of the pitched visual field, the storage of the adaptation process resides in the retinogeniculate system and is manifested in the focal system as a change in luminance threshold and in the ambient system as a change in VPEL. The linear model previously developed to account for VPEL, which was based on the interaction of influences from the pitched visual field and extraretinal influences from the body-referenced mechanism, was employed to incorporate the effects of adaptation. Connections between VPEL adaptation and other cases of perceptual adaptation of visual direction are described.

Adult↗
PubMed1984

Long term cultivation of Plasmodium falciparum in Aotus trivirgatus erythrocytes.

The erythrocytes of the Colombian owl monkey Aotus trivirgatus griseimembra can be used for the long-term in vitro cultivation of Plasmodium falciparum employing a modified Trager -Jensen method. Cultures are grown in HEPES-buffered RPMI-1640 using a 4% suspension of monkey erythrocytes and 10% pooled heat-inactivated human AB serum, with initial parasitemias in a range between 0.2 and 0.5%. Adaptation of new strains from human erythrocytes cultures can be performed by simply subculturing from human to owl monkey erythrocytes in a stepwise manner. When 5% human AB serum is included in cultures to support growth, as much as 5% monkey serum can be added in order to investigate serum effects, such as antibody activity against P. falciparum. The Aotus trivirgatus continuous culture system has provided a stable, consistent source of infected erythrocytes for in vitro experimentation, and the techniques developed have been used to further refine and support the animal experiments in progress.

ABO Blood-Group System↗
PubMedDate not supplied

The fitting of amputated and nonamputated diabetic feet. A French experience at the Villiers-Saint-Denis Hospital.

The Villiers-Saint-Denis Hospital in France specializes in the rehabilitation of and fitting of orthoses for lower-limb amputees, who frequently have diabetes mellitus. The percentage of partial-foot amputations has increased relative to the percentage of transtibial or transfemoral amputations. This article describes a complete range of orthoses and prostheses, adapted to each patient, that allow recovery of the standing position, gait ability, and physical activity.

Amputation, Surgical↗
PubMed1999

[Epidemiological stratification of malaria in the Comoro archipelago].

In the Comoros Islands, the level of malarial endemicity varies greatly from one island to the other, even though the total area (4 islands) covers less than 2,300 km2 and has a population of some 600,000 people only. The epidemiological stratification is based on the diversity of human and physical characterisation. They both determine the presence and the behaviour as well as the size of the vector's populations. Vectorial dynamics can explain varying levels of endemicity given parasitological indicators and specific morbidity. Analyzing these criteria shows up different epidemiological features and serves as a basic guideline for malaria control. The efficiency of this control depends on the relationships between the intensity and the length of the transmission, in the framework of protection mechanisms; it is of crucial importance for clinical treatment. Further elements are the age of the patient, the season and the geographic situation of the area. Stratification provides explanations for these relationships and helps to define antimalarial programmes adapting to each situation a range of therapeutic and antivectorial methods. The availability and accessibility of anti-malarial medicine is the minimum requirement for reducing mortality: domestic spray insecticides for reducing transmission are effective for several years and should be followed by the use of mosquito nets or curtains impregnated with pyrethrinoids, and in the particular case of Grande Comore, the use of larvivorous fish. As anywhere else, the economic development, which is dependent on political stability, is the essential basis for malaria control.

Age Factors↗
PubMed1976

[Isoelectric focusing of complex protein mixtures in the nanogram range in microgels (author's transl)].

A method is described for isolectric focusing of complex protein mixtures in 2, 5 or 10 mul capillaries. For one separation only 15- 50 ng of a protein mixture is needed. Isoelectric focusing is finished after 10 min, staining takes 20 min and destaining approximately 30 min. Using defined mixtures of Servalyt from different pH ranges, isoelectric focusing can be adapted to the protein sample to be fractionated. Protein peaks separated by isoelectric focusing can be electrophoretically eluted and for further analysis refractionated directly in a microgradient gel. The resolution power of microisoelectric focusing is as good as that of the wellknown macroprocedure, as is demonstrated by isoelectric focusing of the water soluble proteins from cerebellum and heart, of rat and human serum and of a human oncocytoma of the thyroid gland.

Animals↗
PubMed2001

Spatiotemporal visual function in tinted lens wearers.

PURPOSE: Tinted lenses have been widely publicized as a successful new treatment for reading disorders and visual stress in children. The present study was designed to investigate a variety of visual deficits reported by children who experience high levels of visual stress and perceptual distortions when reading (Meares-Irlen syndrome; MIS) and to assess the improvements in visual comfort they report when tinted lenses are worn. METHODS: Twenty children (13.1 +/- 0.9 years of age) were recruited who had successfully worn tinted lenses for at least 6 months and were compared with an age-matched control group (12.6 +/- 2.2 years of age) of 21 children who were not lens wearers. A range of psychophysical tasks was adapted to identify specific anomalous visual perceptions. Spatiotemporal contrast sensitivity and contrast increment thresholds were used to investigate subjective reports of dazzle and hypercontrast, and a minimum motion perception (D(min)) and a motion-coherence task were used to assess subjective reports of visual instability and motion. RESULTS: In all viewing conditions (with versus without lens), no selective functional visual loss was demonstrated with any of the tasks used. Psychometric functions also revealed no significant difference between subject groups (control versus MIS). CONCLUSIONS: Under thorough psychophysical investigation, these results revealed no significant difference in visual function between subject group, and this finding is consistent with the absence of any effect of the tinted lenses in the group with MIS.

Adolescent↗
PubMed1975

Gravitational effects on body composition in birds.

Gallinaceous birds, presenting a wide range of body size, were adapted physiologically to hyperdynamic environments, provided by chronic centrifugation. Chemical composition was measured directly on prepared carcasses, which were anatomically comparable, and more amenable to analysis than the intact body. Body mass and body fat decreased arithmetically with increasing field strength and also with increasing body mass. Water content of lean tissue increased in hyperdynamic environments, but irrespectively of body size.

Acceleration↗
PubMed2002

Increased ERG a- and b-wave amplitudes in 7- to 10-year-old children resulting from prenatal lead exposure.

PURPOSE: To determine the dose-response relationship between blood lead concentration ([PbB]) and scotopic ERG amplitude in 7- to 10-year-old children with lifetime lead exposure. METHODS: Full-field flash scotopic ERGs were recorded over a 4-log-unit range in 45 dark-adapted children with normal visual acuity. [PbB] was measured throughout pregnancy and postnatal development, and the subjects' [PbB] levels were grouped at each age by tertiles. RESULTS: The median [PbB] during pregnancy was, from lowest to highest tertile, 2.5 to 5.0, 7.5 to 9.0, and 14.0 to 16.5 microg/dL, and after birth was 4.0 to 8.0, 6.0 to 14.5, and 7.5 to 21.0 microg/dL. Only maternal [PbB] at 12 weeks of pregnancy showed a significant dose-response relationship with the ERG measures, so that with increasing [PbB] there were significant increases in leading-edge a-wave amplitude, peak a-wave amplitude, and b-wave amplitude and sensitivity, with no changes in implicit times. Data analyses showed that children whose mothers had [PbB] of 10.5 microg/dL or more at 12 weeks of pregnancy had relatively increased a- and b-waves. CONCLUSIONS: Lead exposure during the first trimester of pregnancy produces dose-dependent increases in scotopic a- and b-wave amplitudes in 7- to 10-year-old children. The results suggest that the increases in a- and b-wave amplitudes originate from rods; however, the increased b-wave amplitude and sensitivity may also originate in the inner retina. These alterations occurred at maternal [PbB] at or below currently accepted safe levels. These novel findings reveal that the developing retina is a sensitive target for lead and suggest that lead-exposed children be examined for possible future visual system deficits.

Child↗
PubMed1998

[An automatic method segmenting lung regions from digital chest radiograph].

It is difficult to process digital chest image with ordinary method because of the wide dynamic range of chest radiograph. Anatomically adaptive processing is a better method for chest image, but it needs automatic segmentation of the image. In this paper, an effective method for segmenting lung regions from digital chest radiograph is presented. This method automatically calculates the lung/mediastinum-subdiaphragmatic threshold according to the histogram of chest image processed.

Humans↗
PubMed1992

Purification, characterization, and nucleotide sequence of the thermolabile alpha-amylase from the antarctic psychrotroph Alteromonas haloplanctis A23.

The alpha-amylase excreted by the antarctic bacterium Alteromonas haloplanctis was purified and the corresponding amy gene was cloned and sequenced. N- and C-terminal amino acid sequencing were used to establish the primary structure of the mature A. haloplanctis alpha-amylase which is composed of 453 amino acids with a predicted Mr of 49,340 and a pI of 5.5. Three Ca2+ ions are bound per molecule and its activity is modulated by chloride ions. Within the four consensus sequences, Asp-174, Glu-200, and Asp-264 are the proposed catalytic residues. The psychrotrophic A. haloplanctis alpha-amylase is characterized by a high amylolytic activity at low temperatures, a reduced apparent optimal temperature, and typical thermodynamic activation parameters A. haloplanctis alpha-amylase has also a low thermal stability as demonstrated by the temperature effect on both activity and secondary structure. It is suggested that structure flexibility and lower sensitivity of secondary structure to temperature variations in the low temperature range are the main structural adaptations of the psychrotrophic enzyme. The unusual stacking of small amino acids around the catalytic residues is proposed as a factor inducing active site flexibility and concomitant high activity of the enzyme at low temperatures.

Amino Acid Sequence↗
PubMedDate not supplied

[Validation of a Spanish version of the Diagnostic Interview for Bordelines-Revised (DIB-R)].

INTRODUCTION: Borderline Personality Disorder (BPD) is the most studied Axis II disorders. However, there are no Spanish versions of specific interviews. The Diagnostic Interview for Borderlines-Revised (DIB-R) is a semistructured interview used to determine the diagnosis and severity of BPD patients. The aim of this study was to validate the DIB-R for use in a Spanish-speaking sample. METHOD: The psychometric characteristics of the DIB-R Spanish version were assessed in a sample of 156 patients with the possible diagnosis of borderline personality disorder. There were 29 men and 127 women with a mean age of 27.6 years (SD: 6.5; range: 18-45). The Spanish adaptation of the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) was used as gold standard. RESULTS: The DIB-R showed good total internal consistency (Cronbach's alpha: 0.89) and high inter-rater reliability (within-class correlation: 0.94). Using logistic regression analyses the best cut-off was judged to be 6 or more, obtaining high sensitivity (0.81), specificity (0.94) and moderate convergent validity of the diagnosis with the SCID-II (kappa: 0.59). CONCLUSIONS: The Spanish version of the DIB-R showed psychometric characteristics similar to those in the original interview and may be useful to determine BPD presence and severity.

Adolescent↗
PubMed1979

The host/parasite relationships of Xenopsylla astia and X. cheopis on Bandicota bengalensis in Rangoon, Burma.

In Rangoon, Burma, over half the commensal B. bengalensis taken in live traps were found to be infested with Xenopsylla species fleas. X. astia infestations were twice as common as those of the classic plague vector X. cheopis. In terms of absolute numbers X. astia outnumbered X. cheopis by 10 to 1. X. astia was more commonly found as a monospecific infestation, and X. cheopis was more commonly found mixed with X. astia. The flea indicies were high, with a specific index of 2.4 for X. cheopis and 10.2 for X. astia. The flea indicies and flea sex ratios remained stable across the host population and could not be correlated to changes in the head and body length of the host and were not different on male or female hosts. The evidence of this and other surveys is that X. cheopis is not as well adapted for parasitism on free ranging B. bengalensis as is X. astia.

Animals↗