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[In vitro cultivation of Plasmodium falciparum. Applications and limits.- Methodology].

Five years after Trager and Jensen fixed the requirements for a continuous culture of exo-erythrocytic stages in a semisynthetic medium, major advances have been realized. However all practical applications of this method have not yet been investigated. Its main interest is to offer the observation of the intraerythrocytic asexual multiplication and the beginning of the sexual cycle in monitored conditions, beyond the organism regulating processes, and with endless possibility to modify these conditions according to the necessities of the experiment. Compared with the previous use of expensive monkeys, this culture allows a study of P. falciparum in its natural host, cell, the human erythrocyte. It has been already applied for several investigations: - ultrastructure, metabolism, ADN and ARN sequencies of the parasite itself; - the relations between host and parasite (invasion of the erythrocyte by the merozoïte); - constitutional factors of resistance to malaria (hemoglobin S, C, E, deficiency in G6PD, elliptocytosis); - nutritional factors and immunologic defenses (antibodies, cytotoxic cells, ADCC...); - production of plasmodial antigens at the various erythrocytic stages; - chemotherapy (resistance to antimalarial drugs, screening of new drugs and study of their mode of action). The main disadvantages of Trager's and Jensen's method are for one part it concerns the sole erythrocytic stages and for the other part the parasite growth requires components of human origin (serum and erythrocytes). Human serum is hardly adapted to a standardization and appears as the main cause of variations observed in the in vitro proliferation of the parasite. Erythrocytes have a short survival and their metabolism is difficult to separate from that of the parasite. The minor disadvantages of the culture are: - a relative lack of reproductibility which raises difficulties for interpretation of inhibition tests either by antibodies or by antimalarial drugs; - a low output; - a rather expensive cost. Besides, adapting a strain to culture conditions probably induces clone selection (i.e.; loss of protuberances on the erythrocyte membrane). Paradoxically, the successful cultivation of erythrocytic stages raised a need to cultivate the other stages of parasite, that is to say, mainly, the exo-erythrocytic intra-hepatic stages and the sporogonic stages which take place in the mosquito. Somes valuable advances have been recently made in these two ways with animal parasites. The method of culture of P. falciparum has given to all laboratories, even to those out of the endemic area the most valuable opportunity to extend their investigations towards human malaria.

Antimalarials↗

PubMed1990

Diurnal and postural variations in plasma atrial natriuretic factor, plasma guanosine 3':5'-cyclic monophosphate and sodium excretion.

1. We studied diurnal patterns of plasma atrial natriuretic factor, plasma guanosine 3':5'-cyclic monophosphate and urinary sodium excretion in normal subjects after 3 days on a 200 mmol of sodium/60 mmol of potassium diet. On the fourth day blood samples and urine were collected every 3 h. 2. Two studies were performed. In study 1, normal subjects (n = 8) were recumbent for 23 h from 09.00 hours to 08.00 hours the next day. In study 2, normal subjects (n = 10) were permitted to ambulate from 09.00 hours to 23.00 hours and then were recumbent until 08.00 hours the next day. 3. In study 1, assumption of the recumbent posture was associated with increases in plasma atrial natriuretic factor (P less than 0.01), plasma guanosine 3':5'-cyclic monophosphate (P less than 0.05) and urinary sodium excretion (P less than 0.05). 4. In contrast, in study 2 there were no significant changes in plasma atrial natriuretic factor during the day; instead, plasma atrial natriuretic factor increased overnight, reaching a peak at 24.00 hours after 1 h of recumbency (P less than 0.01). A smaller rise in plasma guanosine 3':5'-cyclic monophosphate (P less than 0.05) occurred; urinary sodium excretion decreased markedly (P less than 0.01) and there was no change in creatinine clearance. 5. In both studies, recumbency was associated with an initial drop, followed by a rise, in packed cell volume. 6. These data demonstrate that assumption of the supine position induces a rise in plasma atrial natriuretic factor and accounts for most of the observed variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1983

Mitochondrial DNA differentiation during the speciation process in Peromyscus.

We address the problem of the possible significance of biological speciation to the magnitude and pattern of divergence of asexually transmitted characters in bisexual species. The empirical data for this report consist of restriction endonuclease site variability in maternally transmitted mitochondrial DNA (mtDNA) isolated from 82 samples of Peromyscus polionotus and P. leucopus collected from major portions of the respective species' ranges. Data are analyzed together with previously published information on P. maniculatus, a sibling species to polionotus. Maps of restriction sites indicate that all of the variation observed can be reasonably attributed to base substitutions leading to loss or gain of particular recognition sites. Magnitude of mtDNA sequence divergence within polionotus (maximum approximately equal to 2%) is roughly comparable to that observed within any of five previously identified mtDNA assemblages in maniculatus. Sequence divergence within leucopus (maximum approximately equal to 4%) is somewhat greater than that within polionotus. Consideration of probable evolutionary links among mtDNA restriction site maps allowed estimation of matriarchal phylogenies within polionotus and leucopus. Clustering algorithms and qualitative Wagner procedures were used to generate phenograms and parsimony networks, respectively, for the between-species comparisons. Three simple graphical models are presented to illustrate some conceivable relationships of mtDNA differentiation to speciation. In theoretical case I, each of two reproductively defined species (A and B) is monophyletic in matriarchal genealogy; the common female ancestor of either species can either predate or postdate the speciation. In case II, neither species is monophyletic in matriarchal genotype. In case III, species B is monophyletic but forms a subclade within A which is thus paraphyletic with respect to B. The empirical results for mtDNA in maniculatus and polionotus appear to conform closely to case III. These theoretical and empirical considerations raise a number of questions about the general relationship of the speciation process to the evolution of uniparentally transmitted traits. Some of these considerations are presented, and it is suggested that the distribution patterns of mtDNA sequence variation within and among extant species should be of considerable relevance to the particular demographies of speciation.

Animals↗

PubMed2004

What is the impact of the ACE gene insertion/deletion (I/D) polymorphism on the clinical effectiveness and adverse events of ACE inhibitors?--Protocol of a systematic review.

BACKGROUND: The Angiotensin Converting Enzyme (ACE) insertion/deletion (I/D) polymorphism has received much attention in pharmacogenetic research because observed variations in response to ACE inhibitors might be associated with this polymorphism. Pharmacogenetic testing raises the hope to individualise ACE inhibitor therapy in order to optimise its effectiveness and to reduce adverse effects for genetically different subgroups. However, the extent of its effect modification in patients treated with ACE inhibitors remains inconclusive. Therefore our objective is to quantify the effect modification of the insertion/deletion polymorphism of the angiotensin converting enzyme gene on any surrogate and clinically relevant parameters in patients with cardiovascular diseases, diabetes, renal transplantation and/or renal failure. METHODS: Systematic Review. We will perform literature searches in six electronic databases to identify randomised controlled trials comparing the effectiveness and occurrence of adverse events of ACE inhibitor therapy against placebo or any active treatment stratified by the I/D gene polymorphism. In addition, authors of trials, experts in pharmacogenetics and pharmaceutical companies will be contacted for further published or unpublished data. Hand searching will be accomplished by reviewing the reference lists of all included studies. The methodological quality of included papers will be assessed. Data analyses will be performed in clinically and methodologically cogent subgroups. The results of the quantitative assessment will be pooled statistically where appropriate to produce an estimate of the differences in the effect of ACE inhibitors observed between the three ACE genotypes. DISCUSSION: This protocol describes a strategy to quantify the effect modification of the ACE polymorphism on ACE inhibitors in relevant clinical domains using meta-epidemiological research methods. The results may provide evidence for the usefulness of pharmacogenetic testing for individualised ACE inhibitor therapy.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1994

The effect of hypo-, normo-, and hypercapnia induced by mechanical ventilation on intrapulmonary shunt.

The effects of hypo-, normo- and hypercapnia on the variations in arterial oxygenation and their indices in critical patients with acute respiratory failure (ARF) receiving mechanical ventilation are studied. It is a prospective and randomized study carried out in multidisciplinary ICU. Fifteen ARF patients, intubated and mechanically ventilated, were studied within the first 48 h of evolution. Three stages were delimited: I) 30 min after the beginning of anaesthesia; II) 30 min after adding 30 cm of dead space (VD); III) 30 min after replacing the previous VD with VD of 60 cm. Ventilation parameters and FiO2 were kept stable. Stage I was characterized by respiratory alkalosis and stage II by normal acid-base balance with an increase in PaO2 (p < 0.01) and a decrease in intrapulmonary shunt (Qsp/Qt) (p < 0.001); the indices alveolar to arterial oxygen tension gradient [P(A-a)O2], respiratory index (R.I.) and estimated shunt (Est Shunt) also decreased significantly, whereas arterial to alveolar oxygen tension ratio (PaO2/PAO2) and arterial oxygen tension to inspired oxygen fraction ration (PaO2/FiO2) increased significantly. In stage III there was pure hypercapnic acidosis, with decreases in PAO2 (p < 0.001), P(A-a)O2 (p < 0.01) and R.I. (p < 0.05), while PaO2, Qsp/Qt, Est Shunt, PaO2/PAO2 and PaO2/FiO2 remained stable with respect to the previous situation. The observed PaO2 differs (p < 0.05) from the expected PaO2 in stage III. It is suggested that local or regional modifications of pulmonary perfusion are responsible for the observed variations. The P(A-a)O2 and R.I. indices do not make it possible to differentiate the causes of arterial hypoxemia in the presence of hypercapnia.

Acute Disease↗

PubMed2006

Spot pattern of leopard Danio is caused by mutation in the zebrafish connexin41.8 gene.

Leopard, a well-known zebrafish mutant that has a spotted skin pattern instead of stripes, is a model for the study of pigment patterning. To understand the mechanisms underlying stripe formation, as well as the spot variation observed in leopard, we sought to identify the gene responsible for this phenotype. Using positional cloning, we identified the leopard gene as an orthologue of the mammalian connexin 40 gene. A variety of different leopard alleles, such as leo(t1), leo(tq270) and leo(tw28), show different skin-pattern phenotypes. In this manuscript we show that the mutation in allele leo(t1) is a nonsense mutation, whereas alleles leo(tq270) and leo(tw28) contain the missense mutations I202F and I31F, respectively. Patch-clamp experiments of connexin hemichannels demonstrated that the I202F substitution in allele leo(tq270) disrupted the channel function of connexin41.8. These results demonstrate that mutations in this gene lead to a variety of leopard spot patterns.

Alleles↗

PubMed2006

Physical and microbiological stability of an extemporaneous tacrolimus suspension for paediatric use.

OBJECTIVE: An extemporaneous suspension of tacrolimus for paediatric use has recently been developed but poor bioavailability and erratic plasma concentrations were observed during clinical use. It was not clear whether this was due to changes in the physical properties of the suspension during storage. The aim of this work was to investigate the physical and microbiological stability over the recommended 8-week shelf-life of this extemporaneous tacrolimus suspension. METHODS: Suspensions (0.5 mg/mL) were custom made by a special manufacturer under Good Manufacturing Practice conditions. The procedure involved mixing tacrolimus capsule contents into Ora Plus and Simple Syrup (1 : 1) using a mortar and pestle followed by an homogenization step. The particle sizes of the suspensions were measured using a MasterSizer. A light microscope equipped with polarizers was used to visualize any particle size changes or crystal growth. Viable bacterial and fungal contamination was assessed using standard colony count techniques on solid media. The suspensions were kept at 22-26 degrees C and evaluated weekly. RESULTS: The volume mean diameter d((4,3)) from laser diffraction did not change significantly. Light microscopy did not reveal any significant change in particle size or crystal growth. Contamination by viable and culturable micro-organisms could not be detected. CONCLUSION: The suspension was physically (particle size) and microbiologically stable during the 8-week study period suggesting other factors including poor dosing could be responsible for the pharmacokinetic variation observed during clinical use which warrants further investigation.

Biological Availability↗

PubMed2000

Fowl cholera.

Pasteurella multocida subspecies multocida is the most common cause of fowl cholera, although P. multocida subspecies septica and gallicida may also cause fowl cholera-like disease to some extent. However, the virulence properties of the different subspecies for various hosts have not been elucidated. The severity and incidence of P. multocida infections may vary considerably depending on several factors associated with the host (including species and age of infected birds), the environment and the bacterial strain. No single virulence factor has been associated with the observed variation in virulence among strains. Possible virulence factors include the following: the capsule, endotoxin, outer membrane proteins, iron binding systems, heat shock proteins, neuraminidase production and antibody cleaving enzymes. No RTX toxins (repeats in toxin) appear to be produced by P. multocida, but P. multocida exotoxin (PMT) could contribute to virulence in some avian infections. The epidemiology of fowl cholera appears complex. Traditional serotyping systems are only of limited use in epidemiological studies. In recent years, molecular typing methods have been applied to avian strains of P. multocida of different origin. The results obtained using these newer methods indicate that wild birds may be a source of infection to commercial poultry. Documentation suggesting that mammals play a similar role is not as comprehensive, but the possibility cannot be excluded. Carrier birds seem to play a major role in the transmission of cholera. Surviving birds from diseased flocks appear to represent a risk, but more recent investigations indicate that carriers of P. multocida may exist within poultry flocks with no history of previous outbreaks of fowl cholera. The significance of this awaits further investigation. The site of infection for P. multocida is generally believed to be the respiratory tract. The outcome of infections may range from peracute/acute infections to chronic infections. In the former type of infections, few clinical signs are observed before death and the lesions will be dominated by general septicaemic lesions. In chronic forms of P. multocida infections, suppurative lesions may be widely distributed, often involving the respiratory tract, the conjunctiva and adjacent tissues of the head. Diagnosis is always dependent upon isolation of the organism. For the detection of subclinical infections, mouse passage of relevant samples is recommended, but polymerase chain reaction and isolation attempts on selective media may represent alternatives. Confinement is probably the most effective way to prevent introduction of P. multocida. However, extensive management systems dominate in many parts of the world, and under such circumstances vaccination is recommended as a preventive measure. Unfortunately, the development of safe and efficient live vaccines still poses problems. As a result, control remains dependent on bacterins which exhibit significant disadvantages compared to live vaccines.

Animals↗

PubMed1997

Ontogenetic variation in small-bodied New World primates: implications for patterns of reproduction and infant care.

This paper explores relations of ontogeny, life history strategies and patterns of infant care in 11 species of small-bodied New World monkeys. Analysis of these data suggests that differences in the social systems of Aotus, Callicebus, Saimiri, Callimico, Saguinus, Leontopithecus, Cebuella and Callithrix are closely tied to both the costs of reproduction and to the ontogenetic requirements of maturing young. In Saimiri, both rapid prenatal body weight and perinatal brain growth result in relatively high metabolic costs to breeding females. These costs, coupled with minimal nonmaternal assistance in caregiving, appear to favor a reproductive strategy that limits offspring production to a single birth at 2-year intervals. In contrast, tamarins and marmosets are capable of producing twins twice in the same year. Prenatal investment in each offspring is relatively low, and the potentially high postnatal costs of nursing 2 infants are minimized by the evolution of a social system involving extensive extramaternal care-giving. Cooperative infant care in callitrichins (tamarins and marmosets) serves to distribute the metabolic costs of infant ontogeny among several group members. Callimico is also characterized by a high reproductive output, with females capable of producing a single infant twice during the year. Infants continue to grow rapidly after weaning. Patterns of infant development in Callimico are similar to those found in tamarins and marmosets and support a close phylogenetic relationship among these taxa. Aotus and Callicebus are characterized by an alternative strategy. In these taxa, a monogamous mating system is associated with paternal certainty, male parental care, and provisioning of the young. The transfer of male energetic resources to a single offspring allows night and titi monkeys to maintain a comparatively short interbirth interval (1 year). Ecological and social factors, such as predation and feeding competition, do not appear to adequately explain much of the observed variation in infant development and preadult growth rates in these platyrrhines. Instead, reproductive strategies are strongly linked to ontogenetic patterns and life histories.

Aging↗

PubMed2003

A molecular phylogeography approach to biological invasions of the New World by parthenogenetic Thiarid snails.

The parthenogenetic snail Melanoides tuberculata, present in tropical fresh waters of most of the Old World before 1950, has now invaded the Neotropical area. The phylogeography of this snail was studied to evaluate the pathways and number of such invasions. Because of parthenogenetic reproduction, individuals are structured into genetical clones. Within populations from both the original and invaded areas, several morphologically distinct clones (referred to as morphs) often coexist but the amount of genetic divergence among morphs is unknown. Individuals from 27 morphs and 40 populations world-wide were sequenced at two mitochondrial genes (12S and 16S). Our phylogenetic reconstruction suggests that (i) most of the morphological variation observed in the New World predates invasion, (ii) at least six independent introductions have occurred, and (iii) invasive clones are found throughout most of the phylogenetic tree and do not come from a particular region of the area of origin. Two ideas are discussed in the light of these results. The first lies with the specificities of parthenogenesis in an invasion context. While in sexual species, independently introduced populations eventually merge into a single invasive population, in a parthenogenetic species independently introduced clones have distinct invasion dynamics and possibly exclude each other. Second, although repeated invasions in Melanoides may have an impact on indigenous molluscan faunas, their most likely effect is the world-wide homogenization of the invasive taxon itself.

Animals↗

PubMed2007

Anatomical variations of the cords of brachial plexus and the median nerve.

The variations in formation, location, and courses of the cords of brachial plexus and the median nerve were studied in both axillae of 172 cadavers. The total prevalence of variation was 12.8% (CI, 7.6-17.4) and it was found in 13.2% (CI, 7.5-18) of male and in 10.7% (CI, -0.6-19.6) of female cadavers. These variations were divided into three groups. The first group was abnormal location of the cords, which was either posterolateral or anteromedial in relation to the axillary artery in 2.3% (CI, 0.1-4.5) cadavers. The lateral cord and the medial root of the median nerve had received communicating branches from the posterior cord in most of the cases of this group. The second group was absence of the posterior cord in 3.5% (CI, 0.7-6.1) of cadavers. The lateral and medial cords of this group were connected with the communicating branches, which had a course in front of the axillary artery. The third group was abnormal formation and course of the median nerve in 7% (CI, 3.1-10.6) of cadavers. In all cases of this group the medial root received communicating branch/branches either from the lateral or posterior cord. In eight (4.7%) cadavers, both roots of the median nerve were joined on medial side of the axillary artery to form a median nerve, which traveled medial to the artery. In four (2.3%) cadavers the roots of the median nerve did not join and both traveled separately anteromedial to the axillary and brachial arteries. This study indicates that all three cords and median nerve vary considerably in levels of origin, location and course in relation to the axillary artery and these variable cases were joined with the communicating branch/branches. The observed variations are of anatomical and clinical interest. These kinds of variations are more prone to injury in radical neck dissection and in other surgical operation of the axilla.

Aged↗

PubMed2006

Globally dispersed Y chromosomal haplotypes in wild and domestic sheep.

To date, investigations of genetic diversity and the origins of domestication in sheep have utilised autosomal microsatellites and variation in the mitochondrial genome. We present the first analysis of both domestic and wild sheep using genetic markers residing on the ovine Y chromosome. Analysis of a single nucleotide polymorphism (oY1) in the SRY promoter region revealed that allele A-oY1 was present in all wild bighorn sheep (Ovis canadensis), two subspecies of thinhorn sheep (Ovis dalli), European Mouflon (Ovis musimon) and the Barbary (Ammontragis lervia). A-oY1 also had the highest frequency (71.4%) within 458 domestic sheep drawn from 65 breeds sampled from Africa, Asia, Australia, the Caribbean, Europe, the Middle East and Central Asia. Sequence analysis of a second locus, microsatellite SRYM18, revealed a compound repeat array displaying fixed differences, which identified bighorn and thinhorn sheep as distinct from the European Mouflon and domestic animals. Combined genotypic data identified 11 male-specific haplotypes that represented at least two separate lineages. Investigation of the geographical distribution of each haplotype revealed that one (H6) was both very common and widespread in the global sample of domestic breeds. The remaining haplotypes each displayed more restricted and informative distributions. For example, H5 was likely founded following the domestication of European breeds and was used to trace the recent transportation of animals to both the Caribbean and Australia. A high rate of Y chromosomal dispersal appears to have taken place during the development of domestic sheep as only 12.9% of the total observed variation was partitioned between major geographical regions.

Alleles↗

PubMed1997

Ductal carcinoma in situ. Part 2: Treatment.

Several dilemmas exist when treating a patient with ductal carcinoma in situ (DCIS): the high rate of inter-observer variation for pathologists who must diagnose these tumours; the potential for over- and under-treatment; and the uncertainty about the best way to inform a patient who must often make a decision between breast conservation and mastectomy. Mastectomy is nearly 100% curative, is expedient, but may represent over-treatment for many women, particularly those with asymptomatic mammographically detected lesions. Axillary dissection is not recommended as a routine except for patients with lesions over 5 cm in whom the risk of micro-invasion and lymph node involvement increases. Conservative surgery (CS) alone is associated with a local recurrence rate of approximately 20%, and half of these recurrences (10% overall) are invasive, with a potential long-term cure rate of at least 90%. The addition of radiation to CS reduces the risk of local recurrence to approximately 10%, half of these recurrences (5%) are invasive for a potential long-term cure rate of 95%. Several randomized trials comparing CS with or without radiation therapy (RT) are in progress. The factors that increase the rate of local recurrence after CS alone for DCIS include close or involved margins, and the presence of necrosis or high-grade tumours. Patients with these features should have radiation therapy if breast conservation is preferred. Patients with low-grade tumours (without necrosis) up to 15 mm, with clear margins of at least 10 mm, who agree to be closely observed may be good candidates for CS alone. A critical review of the literature is presented.

Breast Neoplasms↗

PubMed1979

Muscular and other abnormalities in a case of Edwards' syndrome (18-trisomy).

This paper describes the anatomical variations observed in a specimen exhibiting Edwards' Syndrome (18-trisomy). The clinical and autopsy data are compared with those reported in earlier literature. Aside from having a tracheoesophageal fistula, the viscera were characterized by abnormalities of the heart, lungs, liver and kidneys. The facial musculature was relatively undifferentiated. Only a few abnormalities were recorded in the otomandibular and suprahyoid structures. The infrahyoid region had three pairs of supernumerary muscles, including the "sternohyoideus azygos." The bluk of abnormalities were found in the muscles and nerves of the upper limb. These included the absence of the palmaris longus and brevis, the subclavius and the extensor digiti quinti proprius; the presence of supernumerary muscles, e.g., the "rhomboideus occipitalis," the "latissimocondyloideus," and the "subclavius posticus." The deltoid and the pectoralis major were fused to form the "deltopectoral" complex. A definitive musculocutaneous nerve was found in the right arm only. In the lower extremity supernumerary muscles included the "tenuissimus," "peroneus quinti digiti," and the "extensor primi internodii hallucis."

Chromosomes, Human, 16-18↗

PubMed1999

Intraoperative clinical practice and risk of early complications after cataract extraction in the United States, Canada, Denmark, and Spain.

OBJECTIVE: To examine variation in intraoperative clinical practice and rates of adverse events after cataract surgery across four different healthcare systems. DESIGN: Multicenter cohort study. PARTICIPANTS: Patients were recruited from ophthalmic clinics in the United States (n = 75); in the Province of Manitoba, Canada (n = 12); in Denmark (n = 17); and the City of Barcelona, Spain (n = 10). In all, 1420 patients undergoing first eye cataract surgery were enrolled, with preoperative, perioperative, and postoperative clinical data collected on 1344 patients (95%). MAIN OUTCOME MEASURES: Occurrence of 23 specified intraoperative and early postoperative adverse events was measured. Four-month postoperative visual acuity outcome also was measured. RESULTS: Phacoemulsification was performed in two thirds of the extractions in the United States and Manitoba, in one third in Denmark, and in 3% in Barcelona (P < 0.001). More than 96% of extractions in North America and Denmark were performed with the patient under local anesthesia, whereas general anesthesia was used for 38% of extractions in Barcelona (P < 0.001). Rates of intraoperative adverse events were 11% to 12.8% in Manitoba, Denmark, and Barcelona and significantly lower in the United States (6%), mainly because of a lower rate of capsular rupture (P < 0.01). Significantly higher rates of early postoperative events were seen in the United States (18.8%) and Manitoba (20.4%) compared to Denmark (7.9%) and Barcelona (5%) (P < 0.001). The differences among sites in rates of events could not be explained by differences in recorded patient characteristics or surgical techniques. The occurrence of perioperative events was significantly associated with a worse 4-month visual outcome. CONCLUSION: The observed variation in clinical practice might represent a general trend of a slower diffusion of new medical technology in Europe compared with that of North America. Rates of intraoperative and early postoperative events varied significantly across sites.

Aged↗

PubMed2004

Geographic variation in Mexican jays (Aphelocoma ultramarina): local differentiation, polyphyly or hybridization?

Studies of genetic variation within highly variable taxa can provide valuable insight into the factors influencing biological diversification. We examined six microsatellite loci, a nuclear intron and the mitochondrial control region to determine if the Mexican jay subspecies Aphelocoma ultramarina couchii and A. u. potosina have hybridized with western scrub-jays (A. californica). We suspected hybridization because these Mexican Jay populations resemble scrub-jays in several traits. We sampled six Mexican jay (N = 105) and four scrub-jay (N = 78) populations. Suspected hybrid Mexican Jay populations did not share any mitochondrial types or intron alleles with scrub-jays. All microsatellite alleles found in the suspected hybrid Mexican jay populations are also found in the control Mexican jay populations. Genetic distance-based trees from microsatellites supported reciprocal monophyly of Mexican jays and scrub-jays with bootstrap support > 80%. We randomized genotypes among populations to test scenarios consistent with hybridization. In some areas where Mexican jays and scrub-jays occur in sympatry or geographical proximity, randomization tests yield results expected under hybridization (100% support for seven of nine scenarios). However, these populations were not the primary candidates for hybridization based on phenotype. Even if low-level hybridization did occur, hybridization does not appear to be the main reason some Mexican jay populations resemble scrub-jays more than others. The scrub-jay-like traits in these populations may be due to drift, adaptation or plasticity. Alternatively, ancient hybridization, followed by selection for scrub-jay like traits in some Mexican jay populations, might have given rise to the observed variation.

Animals↗

PubMed1995

Variation in the thyrotropic activity of human chorionic gonadotropin in Chinese hamster ovary cells arises from differential expression of the human thyrotropin receptor and microheterogeneity of the hormone.

The role of hCG as a stimulator of the human thyroid has been a subject of controversy, because discrepant results have been obtained in different in vitro assays. In an attempt to explain the variation observed in the thyroid response to hCG, we investigated the ability of hCG and that of its isoforms and glycosylation variants to inhibit [125I]bovine (b) TSH binding and stimulate adenylate cyclase in two clones, JP09 and JP26, of Chinese hamster ovary cells stably transfected with the human TSH receptor (hTSHr). The two clones differed with respect to the number of hTSHr expressed per cell (34,000 in JP09 and 2,000 in JP26 cells). Both responded extremely well to bTSH; the cAMP response to 0.001 IU/L bTSH was distinguishable from basal values. Interestingly, JP09 cells were readily stimulated by hCG (20-100 mg/L; 0.52-2.6 x 10(-6) mol/L) to release cAMP, whereas JP26 cells showed little if any response. Also, cAMP stimulation produced by asialo-hCG was 12-fold in JP09 cells and only 4-fold in JP26 cells compared to 45- and 67-fold stimulations by bTSH, respectively. Stimulation by asialo-hCG was approximately 30% that of bTSH in JP09 cells, but less than 6% in JP26 cells. When assessing the thyrotropic activity of the microheterogeneous isoforms of hCG, more alkaline pI forms were found to be more active than those of a more acidic pI regardless of whether they were derived from normal or molar pregnancy urine. Further studies with hCG, asialo-hCG, asialoagalacto-hCG, and deglycosylated hCG revealed that removal of sialic acid caused a marked increase in both its affinity for hTSHr and its cAMP-releasing potency, whereas removal of further carbohydrate, although it slightly enhanced receptor binding, was detrimental to adenylate cyclase activation. In conclusion, differences in hTSHr expression may cause a variation in the cAMP response to hCG or its glycosylation variants, as does the microheterogeneity of the hormone itself. These mechanisms may be responsible at least in part for the divergent responses of different cell types to hCG and render interpretation of the physiological meaning of the data obtained in recombinant receptor systems difficult.

Animals↗

PubMed1996

[Comparative study of the treatment of postoperative pain in function of the surgical service].

HYPOTHESIS AND OBJECTIVES: A high level of pain has been observed among surgical patients and it has been suggested that surgical specialty may be an important factor in pain, although no relation has been conclusively demonstrated. In this study we compared the characteristics of postoperative pain and pain treatment given in several surgical services. PATIENTS AND METHODS: We studied 249 patients in orthopedic surgery and traumatology (OST, n = 95), general surgery (GS, n = 66), gynecology and obstetrics (GO, n = 51), urology (URO, n = 16), vascular surgery (VS, n = 9), ophthalmology (OPH, n = 7), otorhinolaryngology (ORL, n = 5). The characteristics of analgesic treatment (type of prescription, drug, route, dose and compliance) were recorded, as were degree of pain expressed on a visual analog scale and a verbal assessment scale 24 h after surgery, and level of patient satisfaction with the analgesic treatment. RESULTS: Thirty percent of the patients reported moderate to unbearable pain the day after surgery. Severe pain was most common in OST patients. Analgesics, mainly diclofenac (52%) and pethidine (36%), were prescribed by protocol for 93% of patients. Although there were differences among the various services, compliance with diclofenac prescription was better; compliance was high among GO patients for both drugs. Over half the patients reported having had severe or unbearable pain during the hours following surgery. Most said relief was sufficient or high (55%) with treatment and described themselves as satisfied or very satisfied (62%) with the analgesic received. Surgery on extremities was the most painful and generated the greatest dissatisfaction. CONCLUSIONS: This study suggests that type of surgery may condition the prevalence of and severity of postoperative pain. Although type of surgery and location are important factors, there are sufficient differences and deficiencies in treatment to explain, at least partly, the variation observed.

Adolescent↗