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Preventable trauma deaths: from panel review to population based-studies.

Preventable trauma deaths are defined as deaths which could be avoided if optimal care has been delivered. Studies on preventable trauma deaths have been accomplished initially with panel reviews of pre-hospital and hospital charts. However, several investigators questioned the reliability and validity of this method because of low reproducibility of implicit judgments when they are made by different experts. Nevertheless, number of studies were published all around the world and ultimately gained some credibility, particularly in regions where comparisons were made before and after trauma system implementation with a resultant fall in mortality. During the last decade of century the method of comparing observed survival with probability of survival calculated from large trauma registries has obtained popularity. Preventable trauma deaths were identified as deaths occurred notwithstanding a high calculated probability of survival. In recent years, preventable trauma deaths studies have been replaced by population-based studies, which use databases representative of overall population, therefore with high epidemiologic value. These databases contain readily available information which carry out the advantage of objectivity and large numbers. Nowadays, population-based researches provide the strongest evidence regarding the effectiveness of trauma systems and trauma centers on patient outcomes.

Journal Article↗

Distinctive functional properties of human blood L lymphocytes: a comparison with T lymphocytes, B lymphocytes, and monocytes.

Human blood lymphocytes with high affinity Fc receptors have been operationally named L lymphocytes because of membrane-labile IgG markers. L lymphocytes lack membrane-incorporated immunoglobulin and do not form rosettes with sheep red blood cells coated with IgM antibody and mouse complement. These lymphocytes are capable of binding IgG in normal human serum at 4 degrees C and will form rosettes with human lymphocytes coated with Ripley IgG. In this study, functional in vitro properties of isolated L lymphocytes were compared with T lymphocytes, B lymphocytes, and monocytes. To obtain these mononuclear populations, first, plastic adherent monocytes were harvested. T lymphocytes were then isolated by centrifugation of E rosette-forming cells, and other rosetting techniques were employed to isolate L and B lymphocytes by negative selection. The functional properties of L lumphocytes were completely unlike those of T cells, B cells, or monocytes. L lymphocytes did not proliferate in response to mitogens, soluble antigens, or cell surface antigens. Moreover, this population could not replace monocytes in helping T lymphocytes respond to concanavalin A and pokeweed mitogen. Once T cells were supplemented with monocytes, however, the addition of L lymphocytes to the culture greatly enhanced the T lymphocytes proliferative response to phytohemagglutinin, concanavalinA, purified protein derivative (PPD), and streptokinase/streptodornase. L lymphocytes were not a subset of B cells. They did not spontaneously develop surface Ig in culture, and pokeweek mitogen could not induce them to transform and generate cytoplasmic Ig detectable by immunofluorescence. Mixtures of B cells and T cells responded to pokeweed mitogen better than do T cells alone. In contrast, enhanced reactivity with L and T cell combinations was not observed. Another sharp difference between these two populations was the stimulator capacity of each in mixed lymphocyte culture. When B and L lymphocytes were carefully monocyte-depleted, only B cells were effective stimulators of autologous and allogeneic lymphocytes. In comparison with T cells, B cells, and monocytes, L lymphocytes were the only effective killers of human blood lymphocytes sensitized with IgG. L lymphocytes, then, have cytotoxic potential, but cannot proliferate in response to various stimulants or become antibody-producing cells. These findings suggest that L lymphocytes comprise a third lymphocyte population.

Antigen-Antibody Reactions↗

Risks versus benefits of testosterone therapy in elderly men.

'Andropause', like menopause, has received significant attention in recent years. It results in a variety of symptoms experienced by the elderly. Many of these symptoms are nonspecific and vague. For this reason, many authors have questioned the value of androgen replacement in this population. Also in dispute is the normal cutoff level for testosterone beyond which therapy should be initiated, and whether to measure free or total testosterone. Testosterone levels decline with age, with the lowest level seen in men older than 70 years. This age-related decline in testosterone levels is both central (pituitary) and peripheral (testes) in origin. With aging, there is also a loss of circadian rhythm of testosterone secretion and a rise in sex hormone binding globulin (SHBG) levels. Total testosterone level is the best screening test for patients with suspected hypogonadism. If the total testosterone concentration is low, free testosterone levels should be obtained. Prostate cancer remains an absolute contraindication to androgen therapy. Testosterone replacement results in an improvement in muscle strength and bone mineral density. Similar effects are observed on the haematopoietic system. Data on cognition and lipoprotein profiles are conflicting. Androgen therapy can result in polycythemia and sleep apnoea. These adverse effects can be deleterious in men with compromised cardiac reserve. We recommend that elderly men with symptoms of hypogonadism and a total testosterone level <300 ng/dl should be started on testosterone replacement. This review discusses the pros and cons of testosterone replacement in hypogonadal elderly men and attempts to answer some of the unanswered questions. Furthermore, emphasis is made on the regular follow-up of these patients to prevent the development of therapy-related complications.

Aged↗

Genetic relationships and clonal population structure of serotype 2 strains of Neisseria meningitidis.

Two hundred and thirty-four strains of Neisseria meningitidis, including 94 serotype 2a, 111 serotype 2b, and 19 serotype 2c isolates, together with 10 isolates that were serotyped as 2 with polyvalent antiserum but did not react with monoclonal antibodies, were characterized by the electrophoretic mobilities of 15 metabolic enzymes. Of these enzymes, 14 were polymorphic, and 56 distinctive combinations of alleles at the enzyme loci (electrophoretic types) were identified, among which the mean genetic diversity per locus was 0.413, or about 75% of that recorded for the species N. meningitidis as a whole. Mean genetic diversity among electrophoretic types of the same serotype (2a, 2b, or 2c) was, however, on average, less than half the total species diversity, and no multilocus genotypes were shared between isolates of the different serotypes, which belong to distinctive clonal lineages. Recent temporal changes in the frequencies of recovery of pathogenic strains of serotypes 2a and 2b in South Africa and North America resulted from clone replacement in these populations rather than evolutionary modification of the serotype protein of the initially dominant clones.

Genetic Variation↗

Seasonal recruitment of hippocampal neurons in adult free-ranging black-capped chickadees.

Neurogenesis and neuronal replacement in a population of wild free-ranging animals are described. Our subjects were adult black-capped chickadees (Parus atricapillus). Neuronal birth dates were determined by a single systemic injection of [3H]thymidine, followed by release of the bird and its recapture 6 or more weeks later. Newly formed neurons appeared in the hippocampal complex during all times of year, but with a marked peak in the fall (October). New neurons were also added to the hippocampal complex of captive chickadees, but at levels only half as high as seen in the wild birds. Neurons born at different times of the year lived for a few months and then disappeared. We suggest that the neurons added are part of a process of neuronal replacement and that they are important for the acquisition of new spatial memories, a need that is particularly acute in the fall. Hormonal and experiential factors may determine the rate of neuronal replacement.

Animals↗

Nonmetric cranial trait variation and prehistoric biocultural change in the Azapa Valley, Chile.

Historically, interpretations of both biological and cultural change within the prehistoric Azapa Valley, northern Chile, have cited large-scale population movements, with replacement from complex societies located in the adjacent highlands to the east. Biological estimates of this change have traditionally relied upon biodistance estimates, using craniofacial measures of both deformed and nondeformed skulls. In order to evaluate whether large-scale prehistoric migrations occurred in the Azapa Valley, we examine biodistance results from nonmetric cranial traits for eight mortuary samples that represent all time periods of prehistoric occupation of the valley. None of the mean measures of divergences (MMD) among mortuary samples examined by this study were significant. These results suggest biological continuity in the Azapa Valley during 5,000 years of prehistory, with nonsignificant gene flow during the late Middle Horizon (AD 750-1100) and Late Intermediate (AD 1100-1476) periods. Biodistance results also suggest endogamy within coastal and inland populations. The broader implications of these results are discussed.

Anthropology, Cultural↗

Effects of ribavirin on the development of the Friend leukemia.

Ribavirin (300 and 250 mg/kg i.p., respectively) had a toxic effect on hemopoietic stem cells in normal mice CFU-S, CFU-C, and especially CFU-E were reduced after a single treatment. The drug was further studied in mice infected with the polycythemia-inducing strain of the Friend virus (FV-P). In these mice a specific erythropoietin-independent CFU-E population (CFU-EI) replaces the normal erythropoiesis and can be considered a tumor cell population. With the in vitro technique for CFU-E, CFU-EI can easily be quantified and used as a sensitive marker for the development of the disease. Repeated doses of ribavirin reduced the increase of spleen weight after FV-P infection and the progressive transformation of normal CFU-E into CFU-EI was delayed. The further development of the disease remained unaltered. In vitro CFU-E and CFU-EI were inhibited at the same concentrations when the drug was added to the culture medium. In mice pretreated with multiple doses of hydroxyurea, ribavirin delayed the recurrence of Friend leukemia as seen from the spleen weight increase, but the CFU-E population was predominantly Ep-independent. It is concluded that the effects of the drug were due to its cytotoxicity rather than to a specific antiviral effect.

Animals↗

Hormone replacement therapy and the risk for first hip fracture. A prospective, population-based cohort study.

OBJECTIVE: To determine the relative risk for sustaining a first hip fracture after hormone replacement therapy. DESIGN: Prospective population-based cohort study with an average observation period of 5.7 years. SETTING: A prescription-based cohort in the Uppsala health care region in Sweden. PARTICIPANTS: The cohort (23 246 women) comprised virtually all women of 35 years of age and older who received noncontraceptive estrogens from April 1977 through March 1980. Comparisons were made with women in the background population. MEASUREMENTS: Follow-up through 1983 was done with regard to hospital admissions for a first cervical or trochanteric hip fracture. The observed number of cases was compared with that expected on the basis of person-years of observation in the cohort and incidence rates in the background population. Analyses were made in exposure categories, based solely on prescription data. MAIN RESULTS: During 133 022 person-years of observation, 163 cases of first hip fracture occurred, compared with the 205.5 expected, yielding an overall relative risk of 0.79 (95% CI, 0.68 to 0.93). The greatest protective effect (relative risk, 0.37; CI, 0.13 to 0.79) was found against trochanteric fracture among women receiving potent estrogens who were under 60 years of age at cohort entry. This group also had the highest proportion of treatments with combinations of estrogens and progestogen (41%). Treatment with less potent estrogens, mainly estriols, had no protective effect. Data indicated that the baseline risk for hip fracture was not lower in the cohort women than in the background population. CONCLUSIONS: Treatment with potent estrogens, both alone and possibly when combined with progestogens, reduces the risk for both cervical and trochanteric hip fractures within the first decade after menopause.

Adult↗

Filter Buffy Coats (FBC): a source of peripheral blood leukocytes recovered from leukocyte depletion filters.

In compliance with federal regulations, blood banks routinely use leukocyte depletion filters to eliminate contaminating leukocytes from blood products such as red blood cell and platelet concentrates. We developed and optimized conditions to elute leukocytes adsorbed to these filters; resulting in leukocyte suspensions which we termed Filter Buffy Coats (FBCs). These Filter Buffy Coats can replace standard buffy coats for various research applications. After optimizing both the filter elution medium as well as elution protocols, we compared commonly used leukocyte depletion filters from four different manufacturers. Relative fractions as well as total recoveries of leukocyte subsets, such as lymphocytes, monocytes and granulocytes, found in Filter Buffy Coats were identified and compared among the filters as well as to standard buffy coats and whole blood. Flow cytometric analysis of Filter Buffy Coats confirmed the presence of T- and B-lymphocytes, NK cells and monocytes. Furthermore, a significant quantity of CD34(+) hematopoietic stem or progenitor cells (HSC/HPC) was detected in Filter Buffy Coats prepared from different filters, thus making FBCs a valuable source for research on HSC/HPC. Colony assays revealed that most of these CD34(+) cells are functional. Using immunomagnetic cell sorting (MACS), we isolated a variety of leukocyte populations from FBC mononuclear cells (Filter-PBMCs) including T lymphocytes (CD4(+), CD8(+), CD3(+)), B lymphocytes (CD19(+)), NK cells (CD56(+)), HSC/HPC (CD34(+), CD133(+)) or dendritic cells (BDCA-4(+)). Functional properties of Filter-PBMCs, as well as of some of these isolated leukocyte populations, were confirmed using standard assays. In summary, Filter Buffy Coats are a valuable and convenient source of different peripheral leukocyte populations and can replace standard buffy coat preparations for research applications.

Antigens, CD↗

Proliferation and differentiation of osteoblasts and adipocytes in rat bone marrow stromal cell cultures: effects of dexamethasone and calcitriol.

During bone loss, osteoblast population can be replaced by adipose tissue. This apparent reciprocal relationship between decreased bone density and increased fat formation can be explained by an imbalance in the production of bone-forming and fat-forming cells in the marrow cavity. Thus, osteoblast and adipocyte pathways seem more closely and inversely related. In the present study, we investigated the effects of dexamethasone (dex) and calcitriol [1,25(OH)(2)D(3)] on proliferation and differentiation of osteoblasts and adipocytes in rat bone marrow stromal cell cultures. Stromal cells were grown in primoculture in presence of dex and subcultivated in presence of dex and/or 1,25(OH)(2)D(3). Total cell proliferation, osteoblast and adipocyte-cells number, and -mRNA specific markers were used to study the effects of hormonal treatment on stromal cells. Total cell proliferation was stimulated by dex and inhibited by 1,25(OH)(2)D(3). Dex increased osteoblast and adipocyte cell population whereas calcitriol decreased bone-forming cell number and increased fat cell population. The presence of both hormones led to a strong decrease in osteoblastic cells and to a strong increase in adipocytic cell number. Dex induced mRNA osteoblastic markers expression like bone sialoprotein (BSP) and osteocalcin (OC) and an adipocyte marker expression, the fatty acid binding protein aP2. Calcitriol decreased the dex-induced BSP expression but stimulated slightly OC and aP2 mRNA. The effects of both hormones was to increase strongly OC and aP2 mRNA. These results support that, in rat bone marrow, adipocyte proliferation and differentiation are stimulated by glucocorticoids and calcitriol which act synergically, whereas osteoblastic cell proliferation and differentiation are increased by dex and inhibited by 1,25(OH)(2)D(3).

Adipocytes↗

The incidence of deep vein thrombosis and pulmonary embolism after total knee arthroplasty: the screening study by radionuclide venography.

UNLABELLED: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are considered uncommon in Asian populations and thrombo-prophylaxis is rarely indicated. The objective of this study was to investigate the incidence of DVT and PE after total knee replacement in an Asian population. MATERIAL AND METHOD: There were 100 patients who underwent total knee replacement enrolled in this study. No thrombo-prophylaxis was given to these patients. The possible risk factors such as age, sex, body mass index (BMI), operative time and the post-operative blood loss were recorded. RESULTS: The duplex ultrasonography (controlled) showed no evidence of DVT in all cases. There were 67 patients who completed radionuclide venography in this study. The incidence of DVT from positive radionuclide venography was 24% (16/67 patients) and PE was 12% (8/67 patients). All patients with positive imaging studies were asymptomatic. The risk factors were similar in both groups. CONCLUSION: The incidence of DVT and PE in post-operative total knee replacement surgery, although lower than the incidence in Western populations, is higher than previously assumed. The radionuclide venography is less invasive and a useful diagnostic method for both DVT and PE. Because all patients with DVT and PE are asymptomatic, the use of thrombo-prophylaxis should be considered for risk and benefit.

Aged↗

Quality of life in patients with bioprostheses and mechanical prostheses. Evaluation of cohorts of patients aged 51 to 65 years at implantation.

BACKGROUND: The purpose of this study was 3-fold: to compare the quality of life (QOL) in age- and sex-matched patients who received biological and mechanical prosthetic valves in isolated aortic valve replacement, to compare the QOL of patients with aortic valve replacement with the general population, and to compare patients with biological and mechanical prostheses with certain valve-specific questions and relate these responses to overall QOL. METHODS AND RESULTS: Patient-perceived QOL was evaluated in 200 patients who were sampled from a population of 420 patients (age range 51 to 65 years) who underwent isolated aortic valve replacement in the period of 1986 to 1996. One hundred of the sampled patients had a mechanical valve inserted and an equal number had porcine bioprostheses. Three survey instruments were used to examine perceived QOL: the SF-12 form, a 7-valve specific question form, and the Lamy Smiley Faces form. The response to the questionnaires was 89.5% (179 patients). Patients with mechanical valves were more bothered by valve sounds (P < 0.01) and had a negative correlation (P < 0.01) between valve sound and QOL on the mental scale only. Patients with biological valves were more fearful of the need for reoperation (P < 0.01), but there was no correlation between fear and QOL. The mechanical valve group had a negative correlation (P < 0.01) between fear of reoperation and QOL on both the mental and physical scales. There was no difference between the 2 cohorts with respect to fear of valve failure. Patients with mechanical valves were more concerned about frequency of medical visits and blood tests (P < 0.01) as well as the possibility of anticoagulant-related bleeding events (P < 0.01). QOL was equivalent between the 2 groups and to the general population for the same age group. Ninety-seven percent of the patients indicated they would make the same surgical decision again with regard to valve replacement; there was no difference between the 2 valve groups on this question. CONCLUSIONS: Patient-perceived QOL is similar between patients with aortic mechanical and biological valve replacement in the studied age group and comparable to the general population of similar age. Although certain valve-specific differences exist between the 2 prosthetic types, these differences do not appear to affect overall QOL as described by these patients.

Aged↗

[How WHI study influences women doctors' behaviour towards menopause].

OBJECTIVE: A survey entitled FEMME was conducted during 2002 in order to evaluate among French women doctors their own actual or future menopause perception and this before the WHI publication. The results of this American trial possibly modified the perception of these French women doctors. Therefore the same experts group conducted a new survey, from May to September 2003. The main aim of this survey was to evaluate the possible changes in the medical management of the actual or future menopause of these women, and secondarily to evaluate the changes in their patients' behaviour towards hormone replacement therapy (HRT). POPULATION AND METHODS: Postal auto administered questionnaires were sent to the same 10 000 French women doctors (GP or gynaecologist) whatever their menopausal status or their age. 1365 women doctors (respectively 18,5 or 11% of the gynaecologists or GPs contacted) were volunteers to participate in this survey. Among them, 1120 (84,9%) had already participated in the first part of this survey which took place before the WHI publication. RESULTS: 80% of these women doctors have been informed on WHI results principally by professional press or conferences. 70,9% changed their own actual or future menopause perception as follows. No additional selection of non hormonal treatment have been mentioned in comparison with the first part of the survey. On the other hand for HRT, selections of free estrogen plus progestin associations increased whereas those of fixed combinations decreased: this might be linked to the greater variety of estrogen doses, types of progestin and schedules of treatment (mostly with bleeding) offered by this kind of associations. Finally, duration of HRT is included between three and ten years in most cases. DISCUSSION AND CONCLUSION: Thus, unlike most of their patients, these women's physicians always preferred hormonal treatment for their own actual or future menopause. Only the conditions of these treatments have changed.

Attitude of Health Personnel↗

Long-term outcome of total knee replacement: does obesity matter?

BACKGROUND: Although arthritic complications are common in the obese, many surgeons are reluctant to perform joint replacements in this population. We compared outcomes of total knee arthroplasties (TKAs) in normal weight and obese patients. METHODS: 30 TKAs in 21 obese patients with BMI 30-49 (Group A--mainly mildly and moderately obese) were compared to a matched group of 53 TKAs in 41 non-obese patients with BMI 16-29.9 (Group B). Outcome measures included the Knee Society Score (a composite of clinical and functional parameters), radiographic results, and the need for revision or reoperation. RESULTS: Median follow-up was 11.3 years; no patients were lost to follow-up during this time. The Knee Society Score rose 92 points in Group A to a final score of 184, and 95 points in Group B to a score of 193. There was no statistical difference in Groups A and B between the improvement in scores or the final score achieved. Osteolysis rates were not significantly different between the 2 groups (5% vs 13%), nor were radiolucency rates (0% vs 9.7%). Median alignment was also similar in both groups (8.1 degrees vs 8.0 degrees valgus). 13.3% of Group A required reoperation while none required revision, and 13.2% of Group B required reoperation with 3.8% requiring revision. Survival rates were similar in both groups (71.4% vs 61.5%). CONCLUSIONS: Moderate obesity does not affect the clinical and radiologic outcome of TKA. However, TKA results in improved mobility, enhancing the success of subsequent weight loss therapy.

Adult↗

Body composition and physical fitness are major determinants of the growth hormone-insulin-like growth factor axis aberrations in adult Turner's syndrome, with important modulations by treatment with 17 beta-estradiol.

The objectives of this study were to 1) study the GH-insulin-like growth factor (IGF) axis in adult untreated Turner's syndrome compared to that in age-matched controls; 2) examine the effects of sex hormone substitution on this axis, 3) study the effects of route of administration of 17 beta-estradiol on the measured variables, and 4) examine the effects of sex steroids on hepatic function in Turner patients. Twenty-seven patients with Turner's syndrome were evaluated before and during sex hormone replacement, and an age-matched control group (n = 24) was evaluated once. Main outcome variables were GH and other measures of the GH-IGF axis, body composition, maximal oxygen uptake, sex hormone-binding globulin, and hepatic enzymes and proteins. The integrated 24-h GH concentration (IC-GH; micrograms per L/24 h) was reduced in women with Turner's syndrome (T) compared to controls [C; mean +/- SD, 18.3 +/- 12.0 (T) vs. 37.2 +/- 29.7 (C); P = 0.007]. However, multiple regression revealed that fat-free mass (FFM) and maximal oxygen uptake were significant explanatory variables (joint r = 0.77; P < 0.0005), accounting for 60% of the variance in the 24-h IC-GH. This association was also present in controls. After adjustment for these two variables, any difference in GH concentration between Turner patients and controls disappeared. Serum IGF-I and IGF-II were identical in Turner patients and controls despite the difference in 24-h IC-GH. The level of GH-binding protein (GHBP; nanomoles per L) was higher in Turner women [1.87 +/- 0.72 (T) vs. 1.22 +/- 0.33 (C); P = 0.0005]; after adjustment for FFM, the difference in GHBP levels disappeared between Turner patients and controls. During sex hormone treatment a significant increase was seen in the 24-h IC-GH (P = 0.02), FFM (percentage of weight; P < 0.0005) and maximal oxygen uptake (milliliters of O2 per kg/min; P = 0.02). Serum IGF-I was unchanged, whereas serum IGF-II (micrograms per L) decreased significantly [Turner, basal (TB), vs. Turner, treatment (TT), 860 +/- 135 vs. 823 +/- 150; P = 0.04]. Alanine aminotransferase (units per L), gamma-glutamyl transferase (units per L), and alkaline phosphatase (units per L) were significantly elevated during the basal study period, and all decreased during treatment [alanine amino-transferase, 55 +/- 55 (TB) vs. 30 +/- 20 (TT; P = 0.006); gamma-glutamyl transferase, 92 +/- 98 (TB) vs. 43 +/- 65 (TT; P = 0.003); alkaline phosphatase, 211 +/- 113 (TB) vs. 175 +/- 54 (TT); P = 0.06]. The route of administration of 17 beta-estradiol did not affect its actions. In conclusion, we found the GH-IGF axis in Turner's syndrome to be normal, with body composition and physical fitness exerting the same modifying effects on this axis as seen in the normal population. Sex hormone replacement in Turner's syndrome is associated with normalizing effects on the GH-IGF axis, body composition, physical fitness, and hepatic function. The lowering of hepatic enzymes is a surprising and hitherto undiscovered action of sex steroids. Finally, the route of administration of 17 beta-estradiol is of minor importance in Turner's syndrome.

Adult↗

Anatomical basis of a congenital hearing impairment: basilar papilla dysplasia in the Belgian Waterslager canary.

Recent investigations into the anatomy of the inner ear of Belgian Waterslager canaries (BWC) have demonstrated myriad malformations associated with dysgenesis of the pars inferior of the otocyst. In those studies, the surface anatomy of BWC's basilar papilla and sacculus was examined utilizing scanning electron microscopy. In the present investigation, we utilized both light microscopy and transmission electron microscopy to describe the cross sectional anatomical pathology of the BWC's basilar papilla. Examination of the BWC's organ of Corti revealed numerous dysmorphologies: 1) hair cells from the tall hair cell region appeared broad and stunted, with deformed cuticular plates, abnormal stereocilia, and recognizable microvilli; 2) quantitative analysis of these hair cells revealed disproportionately large nuclei and abnormally short stereocilia; 3) hair cells from the short hair cell region of the papilla were absent, replaced by a population of large cells with electron-lucent cytoplasm; and 4) the tectorial membrane in the BWC papilla was narrow, covering only the area where the deformed tall hair cells were found. The malformations appeared to be more severe at the apex and midsection of the basilar papilla than at the base. These observations allow us to suggest a hypothesis to account for the distinct anatomofunctional hearing deficit observed in these birds. In addition, they further support our hypothesis that the inner ear of BWC is afflicted by a disorder similar to Scheibe's dysplasia, the most common inner ear defect associated with congenital hearing loss in humans.

Animals↗

Neuroblast protuberances in the subventricular zone of the regenerative MRL/MpJ mouse.

The MRL mouse is unique in its capacity for regenerative healing of wounds. This regenerative ability includes complete closure, with little scarring, of wounds to the ear pinna and repair of cardiac muscle, without fibrosis, following cryoinjury. Here, we examine whether neurogenic zones within the MRL brain show enhanced regenerative capacity. The largest neurogenic zone in the adult brain, the subventricular zone (SVZ), lies adjacent to the lateral wall of the lateral ventricle and is responsible for replacement of interneuron populations within the olfactory bulb. Initial gross observation of the anterior forebrain in MRL mice revealed enlarged lateral ventricles; however, little neurodegeneration was detected within the SVZ or surrounding tissues. Instead, increased proliferation within the SVZ was observed, based on incorporation of the thymidine analogue bromodeoxyuridine. Closer examination using electron microscopy revealed that a significant number of SVZ astrocytes interpolated within the ependyma and established contact with the ventricle. In addition, subependymal, protuberant nests of cells, consisting primarily of neuroblasts, were found along the anterior SVZ of MRL mice. Whole mounts of the lateral wall of the lateral ventricle stained for the neuroblast marker doublecortin revealed normal formation of chains of migratory neuroblasts along the entire wall and introduction of enhanced green fluorescent protein-tagged retrovirus into the lateral ventricles confirmed that newly generated neuroblasts were able to track into the olfactory bulb.

Animals↗

Transition stages of molecular drive in multiple-copy DNA families in Drosophila.

Multigene and non-genic DNA families are in a state of turnover and hence are continually being replaced throughout a population by new variant repeats. To quantify such molecular processes, in the absence of selection, it is necessary to find and compare stages of transistion during the homogenization of at least two non-genic families evolving in parallel in a closely related group of species. Detailed sequence analysis of patterns of variation, at each nucleotide position considered independently, amongst repeats of two tandem DNA families from seven related Drosophila species, reveals all stages of transition during the spread of randomly produced variant repeats. Variant repeats are found at different stages of homogenization and fixation in a population, irrespective of the loci, chromosomes or individuals from which they were cloned. Differences between the families in the relatively small number of variants at each transition stage and the greater number of fully homogenized and fixed variants between species of greater divergence indicate that the process of spread (molecular drive) is rapid relative to the mutation rate and occurs at seemingly different constant rates for each family. Occasional gene conversions, in addition to unequal exchanges, have contributed to family turnover. The significance of these results to the evolution of functional multigene families and divergence and conservation of sequences is discussed.

Journal Article↗