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Biomedical subjects

J I Hoffman

Publications and source records attributed to J I Hoffman.

At least 19 recordsLinked to original sources
PubMed2006

No relationship between microsatellite variation and neonatal fitness in Antarctic fur seals, Arctocephalus gazella.

Published studies of wild vertebrate populations have almost universally reported positive associations between genetic variation measured at microsatellite loci and fitness, creating the impression of ubiquity both in terms of the species and the traits involved. However, there is concern that this picture may be misleading because negative results frequently go unpublished. Here, we analyse the relationship between genotypic variation at nine highly variable microsatellite loci and neonatal fitness in 1070 Antarctic fur seal pups born at Bird Island, South Georgia. Despite our relatively large sample size, we find no significant association between three different measures of heterozygosity and two fitness traits, birth weight and survival. Furthermore, increasing genetic resolution by calculating parental relatedness also yields no association between genetic variation and fitness. Our findings are consistent with necropsy data showing that most pups die from starvation or trauma, conditions that are unlikely to be influenced strongly by genetic factors, particularly if the benefits of high heterozygosity are linked to immune-related genes.

Animals↗
PubMed2006

Deep genetic subdivision within a continuously distributed and highly vagile marine mammal, the Steller's sea lion (Eumetopias jubatus).

The Steller's sea lion Eumetopias jubatus is an endangered marine mammal that has experienced dramatic population declines over much of its range during the past five decades. Studies using mitochondrial DNA (mtDNA) have shown that an apparently continuous population includes a strong division, yielding two discrete stocks, western and eastern. Based on a weaker split within the western stock, a third Asian stock has also been defined. While these findings indicate strong female philopatry, a recent study using nuclear microsatellite markers found little evidence of any genetic structure, implying extensive paternal gene flow. However, this result was at odds with mark-recapture data, and both sample sizes and genetic resolution were limited. To address these concerns, we increased analytical power by genotyping over 700 individuals from across the species' range at 13 highly polymorphic microsatellite loci. We found a clear phylogenetic break between populations of the eastern stock and those of the western and Asian stocks. However, our data provide little support for the classification of a separate Asian stock. Our findings show that mtDNA structuring is not due simply to female philopatry, but instead reflects a genuine discontinuity within the range, with implications for both the phylogeography and conservation of this important marine mammal.

Animals↗
PubMed2006

Dispersal, philopatry and intergroup relatedness: fine-scale genetic structure in the white-breasted thrasher, Ramphocinclus brachyurus.

Dispersal is a fundamental process influencing evolution, social behaviour, and the long-term persistence of populations. We use both observational and genetic data to investigate dispersal, kin-clustering and intergroup relatedness in the white-breasted thrasher, Ramphocinclus brachyurus, a cooperatively breeding bird that is globally endangered. Mark-resighting data suggested sex-biased dispersal, with females dispersing over greater distances while males remained philopatric. Accordingly, spatial autocorrelation analysis showed highly significant fine-scale genetic structure among males, but not among females. This fine-scale genetic structuring of the male population resulted in very high levels of relatedness between dominant males at neighbouring nests, similar to that seen within cooperative groups in many species where kin selection is cited as a cause of cooperation. By implication, between-group as well as within-group cooperation may be important, potentially creating a feedback loop in which short-distance dispersal by males leads to the formation of male kin clusters that in turn facilitate nepotistic interactions and favour further local recruitment. The strength of spatial autocorrelation, as measured by the autocorrelation coefficient, r, was approximately two to three times greater than that reported in previous studies of animals. Relatively short dispersal distances by both males and females may have a negative impact on the white-breasted thrasher's ability to colonize new areas, and may influence the long-term persistence of isolated populations. This should be taken into account when designating protected areas or selecting sites for habitat restoration.

Animal Migration↗
PubMed2006

Genetic tagging reveals extreme site fidelity in territorial male Antarctic fur seals Arctocephalus gazella.

Genetic tagging, the identification of individuals using their genotypes, provides a powerful tool for studying animals that are difficult to observe or identify using conventional techniques. However, despite being widely adopted by conservation biologists, the full potential of this approach has yet to be realized. Here we used genetic recapture data to quantify male site fidelity at a colony of Antarctic fur seals where an aerial walkway provides unprecedented access and individual positions are determined daily to 1 m accuracy. Because males are too large and aggressive to be captured and fitted with conventional tags, we remotely collected 770 tissue samples over eight consecutive seasons and used nine-locus microsatellite genotypes to reveal 306 genetic recaptures among 464 unique individuals. Within seasons, males are highly site-faithful, with any movements that occur tending to take place before the period when females come into oestrus. Of those males that return to breed over successive seasons, almost half return to within a body length of where they were before. The discovery of such extreme site faithfulness has implications for the population structure and mating system of fur seals and potentially other colonially breeding species.

Animals↗
PubMed2005

Microsatellite genotyping errors: detection approaches, common sources and consequences for paternal exclusion.

Microsatellite genotyping errors will be present in all but the smallest data sets and have the potential to undermine the conclusions of most downstream analyses. Despite this, little rigorous effort has been made to quantify the size of the problem and to identify the commonest sources of error. Here, we use a large data set comprising almost 2000 Antarctic fur seals Arctocephalus gazella genotyped at nine hypervariable microsatellite loci to explore error detection methods, common sources of error and the consequences of errors on paternal exclusion. We found good concordance among a range of contrasting approaches to error-rate estimation, our range being 0.0013 to 0.0074 per single locus PCR (polymerase chain reaction). The best approach probably involves blind repeat-genotyping, but this is also the most labour-intensive. We show that several other approaches are also effective at detecting errors, although the most convenient alternative, namely mother-offspring comparisons, yielded the lowest estimate of the error rate. In total, we found 75 errors, emphasizing their ubiquitous presence. The most common errors involved the misinterpretation of allele banding patterns (n = 60, 80%) and of these, over a third (n = 22, 36.7%) were due to confusion between homozygote and adjacent allele heterozygote genotypes. A specific test for whether a data set contains the expected number of adjacent allele heterozygotes could provide a useful tool with which workers can assess the likely size of the problem. Error rates are also positively correlated with both locus polymorphism and product size, again indicating aspects where extra effort at error reduction should be directed. Finally, we conducted simulations to explore the potential impact of genotyping errors on paternity exclusion. Error rates as low as 0.01 per allele resulted in a rate of false paternity exclusion exceeding 20%. Errors also led to reduced estimates of male reproductive skew and increases in the numbers of pups that matched more than one candidate male. Because even modest error rates can be strongly influential, we recommend that error rates should be routinely published and that researchers make an attempt to calculate how robust their analyses are to errors.

Animals↗
PubMed2001

Exercise-induced hyperemia unmasks regional blood flow deficit in experimental hindlimb ischemia.

UNLABELLED: Many experimental models of hindlimb ischemia are characterized by spontaneous and rapid normalization of resting muscle blood flow (BF) rates which complicates the long-term evaluation of angiogenic therapies to reverse limb ischemia. We tested the hypothesis that peroneal nerve stimulation in an ischemic hindlimb would increase the oxygen (O(2)) demand and BF rate, thereby unmasking a severe blood flow deficit that is not apparent at rest. METHODS: Ischemia was induced in adult rats by ligation of the left common iliac, femoral arteries, and their branches. Peroneal nerves were stimulated to allow measurement of exercise-induced regional BF rates with fluorescent microspheres. Hemodynamics were monitored. Fluorescent microspheres were injected before and after 5 min of nerve stimulation 3, 10, and 24 days postischemia. The tibialis anterior (TA) and gastrocnemius (GC) muscles and skin were harvested and weighed, and fluorescence was measured. BF rate was calculated as milliters per minute per gram of tissue and compared to normal muscle and skin of unoperated control rats. In order to determine the accuracy of BF rate measurements in ischemic muscle when <400 microspheres was delivered per specimen, 3 rats were studied by simultaneous injection of 4 x 10(5) blue and 1 x 10(5) yellow-green fluorescent microspheres. The correlation coefficient between the number of different colored microspheres delivered was measured. RESULTS: The ischemia caused atrophy of the TA and GC muscles. The mean muscle mass of the ischemic TA and GC as a percentage of total body weight decreased over time vs control [TA 0.13 +/- 0.05% vs 0.25 +/- 0.03%, P < 0.05; GC 0.51 +/- 0.27% vs 0.70 +/- 0.07%, P = 0.07 at 24 days (24D)]. Despite clinical evidence of severe hindlimb ischemia in experimental groups, i.e., pressure sores, muscle atrophy, and weakness, resting BF rates were not significantly different from those of control. The BF rate of the TA was of 0.11 ml/min/g after 3D of ischemia, 0.14 ml/min/g after 10D, and 0.13 ml/min/g after 24D. The mean BF rate in normal muscle of unoperated controls was 0.16 ml/min/g (P > 0.05). However, the exercise-induced hyperemia in the skeletal muscle was significantly blunted in all of the ischemic groups. The unoperated control TA had a greater than 10-fold increase in BF to 1.95 ml/min/g in response to exercise while the ischemic TA had no increase in BF at 3D, 2-fold increase at 10D, and a 5-fold increase at 24D. Parallel findings were noted in the GC muscles. There was no significant difference in the BF rate in the skin. The accuracy of this microsphere technique in measuring very low BF rates found in ischemic muscle was supported by the significant correlation coefficient (r = 0.99) comparing two quantities of microspheres injected simultaneously. CONCLUSION: Despite clinical signs of severe hindlimb ischemia, resting BF rates in the ischemic groups were not significantly decreased. Peroneal nerve stimulation resulted in up to 10-fold increase in BF rate and unmasked a severe deficit in vascular reserve in the ischemic groups. Resting BF rate is not always an accurate reflection of the flow deficit in models of critical limb ischemia, and this model of exercise-induced hindlimb hyperemia may allow better long-term evaluation of angiogenic therapies designed to reverse critical limb ischemia.

Animals↗
PubMed2001

Evaluation of fetal heart dimensions from 12 weeks to term.

To evaluate whether fetal cardiac measurements can be made in the second trimester, we examined a cohort of normal pregnancies between 12 and 18 weeks' gestation using state-of-the-art ultrasound equipment. We examined this population longitudinally at intervals of 2 weeks, as well as at 32 weeks' gestation. From the 4-chamber view we measured the ventricular and atrial cavity dimensions, the thickness of the ventricular walls and septum at end-diastole, and the annulus dimensions of the mitral and tricuspid valves. Using a variety of views we also measured the long and cross-sectional diameters of the atria, the aorta, the pulmonary artery and its main left and right branches, the ductus arteriosus, and the superior and inferior vena cavae. To test the frequency with which measurements could be made, we divided them into measurements that were clear and easy to define (statistically good), to those that were unclear (statistically bad), or those that were not measured at all (none). Data were then analyzed by regression analysis, analysis of variance, and covariance. The frequency of reliable measurements varied inversely with gestational age. The inflection point for measurements was approximately at 16 weeks. Data from this longitudinal study were evaluated against those obtained from our previous study. Because no statistical differences were found in measurements between these studies where they overlapped, the data were pooled into 1 large group and the mean and SEEs calculated for all variables. Our study demonstrates that with current transabdominal imaging, fetal cardiac measurements can be made reliably in normal fetuses from 16 weeks' gestation onward. The frequency of obtaining data in younger normal fetuses suggests it is unlikely that reliable observations can be made routinely in abnormal fetuses < 16 weeks old, although this might be possible in individual fetuses.

Echocardiography↗
PubMed2001

The structure and function of the helical heart and its buttress wrapping. VII. Critical importance of septum for right ventricular function.

The macroscopic structure of the right ventricle includes a transverse basal loop for the free wall, and oblique septal components, originating from the descending and ascending segments of the apical loop. Data is presented that determines why right ventricular function is related principally to intraventricular septal function, and why right ventricular failure is magnified by septal stunning caused by poor myocardial protection. The background of this architectural/functional change can explain normal right ventricular function, the relationship of right ventricular performance to pulmonary vascular resistance, experimental studies that characterize right ventricular performance after architectural free wall ablation, right ventricular disconnection, right coronary occlusion, and free wall replacement. These basic science studies are related to perioperative right ventricular performance, involving methods of myocardial protection, protamine reaction, right coronary occlusion and reperfusion, right ventricular dyskinesia, chronic aortic and mitral valve replacement (MVR) replacement, congenital heart disease, right and left ventricular assist devices (LVADs), and transplantation. The predominant focus is related to the septum and how it can be evaluated perioperatively. Septal evaluation by echocardiogram should become an essential feature during intraoperative management.

Cardiovascular Diseases↗
PubMed2001

Population genetics of the schistosome intermediate host Biomphalaria pfeifferi in the Zimbabwean highveld: implications for co-evolutionary theory.

Co-evolutionary theory proposes that polymorphisms in co-evolved traits may be maintained through differential selection in spatially heterogeneous environments. Spatial heterogeneity of the schistosome intermediate host, Biomphalaria pfeifferi, was investigated here, using RAPD markers. Overall, 256 individuals, collected at 32 sites on 13 rivers in the Chiweshe region of Zimbabwe, were analysed. Significant genetic differentiation was demonstrated, both between populations from the different rivers and between populations collected at different sites on each of several of the rivers investigated. However, the presence of spatial differentiation between populations from individual rivers varied with river type. It was not apparent in permanent, deep, fast-flowing rivers, where high levels of migration, through passive dispersal along the rivers, are likely. The snails collected from shallow, semi-permanent rivers not only showed relatively high levels of population subdivision but also high levels of within-site genetic diversity, consistent with the existence of 'co-evolutionary hot-spots' where schistosome infection may be prevalent. These results are discussed with reference to the population biology of B. pfeifferi and to host-parasite co-evolution.

Analysis of Variance↗
PubMed2000

Problems of coronary flow reserve.

Coronary flow reserve is used to aid understanding why myocardial oxygen consumption may fail to meet demand. Its general aspects are well known, but the problems of using it are not. This manuscript describes three important factors that need to be considered when assessing coronary flow reserve. (1) Maximal flow is usually achieved by giving either increasing doses or else what is thought to be a maximal dose of a vasodilator, or by examining peak reactive hyperemia. Evidence that both these approaches are flawed is provided. (2) Existing methods in humans allow only total reserve to be determined, but this might be inadequate because changes in total reserve might not reflect changes in subendocardial flow reserve. (3) Because there is marked heterogeneity of flow reserve in the left ventricle, measuring total flow reserve does not indicate when small regions are becoming ischemic. More basic research is needed to overcome these difficulties.

Animals↗
PubMed2000

Effects of increased pressure inside or outside ventricles on total and regional myocardial blood flow.

Increasing pressures to 30 mmHg in right (RV) and left (LV) ventricles and surrounding heart (SH) in isolated, arrested, maximally vasodilated, blood-perfused dog hearts shifted pressure-flow (PF) curves rightward and increased zero flow pressure (P(zf)) by an amount equal to the RV applied pressure, SH applied pressure, or two-thirds of the LV applied pressure. There were comparable increases in coronary venous pressures. Increasing LV or SH pressures decreased coronary blood flows, especially in the subendocardium. Decreases in driving pressure decreased flows in all layers, but even with driving pressure of 5 mmHg, a few subepicardial pieces had flow. We conclude with the following: 1) raising pressures inside or outside the heart shifts PF curves and raises P(zf) by increasing coronary venous pressure; 2) the effects are most prominent in the subendocardial muscle layer; and 3) as driving pressures are decreased, there is a range of P(zf) in the heart with the final P(zf) recorded due to the last little piece of muscle to be perfused.

Animals↗
PubMed1999

The Mitral Regurgitation Index: an echocardiographic guide to severity.

OBJECTIVES: The purpose of this study was to develop a semiquantitative index of mitral regurgitation severity suitable for use in daily clinical practice and research. BACKGROUND: There is no simple method for quantification of mitral regurgitation (MR). The MR Index is a semiquantitative guide to MR severity. The MR Index is a composite of six echocardiographic variables: color Doppler regurgitant jet penetration and proximal isovelocity surface area, continuous wave Doppler characteristics of the regurgitant jet and tricuspid regurgitant jet-derived pulmonary artery pressure, pulse wave Doppler pulmonary venous flow pattern and two-dimensional echocardiographic estimation of left atrial size. METHODS: Consecutive patients (n = 103) with varying grades of MR, seen in the Adult Echocardiography Laboratory at UCSF, were analyzed retrospectively. All patients were evaluated for the six variables, each variable being scored on a four point scale from 0 to 3. The reference standards for MR were qualitative echocardiographic evaluation by an expert and quantitation of regurgitant fraction using two-dimensional and Doppler echocardiography. A subgroup of patients with low ejection fraction (EF < 50%) were also analyzed. RESULTS: The MR Index increased in proportion to MR severity with a significant difference among the three grades in both normal and low EF groups (F = 130 and F = 42, respectively, p < 0.0001). The MR Index correlated with regurgitant fraction (r = 0.76, p < 0.0001). An MR Index > or =2.2 identified 26/29 patients with severe MR (sensitivity = 90%, specificity = 88%, PPV = 79%). No patient with severe MR had an MR Index <1.8 and no patient with mild MR had an MR Index >1.7. CONCLUSIONS: The MR Index is a simple semiquantitative estimate of MR severity, which seems to be useful in evaluating MR in patients with a low EF.

Adult↗
PubMed1998

Echocardiographic hemodynamic and morphometric predictors of survival after two-ventricle repair in infants with critical aortic stenosis.

OBJECTIVES: The purpose of this study was to identify echocardiographic hemodynamic and morphometric factors that would predict which infants with critical aortic stenosis could undergo relief of left ventricular outflow obstruction as opposed to the Norwood procedure. BACKGROUND: Echocardiographic predictors of survival in infants with critical aortic stenosis after two-ventricle repair have been mainly limited to morphometric factors, which have limitations. Echocardiographic hemodynamic predictors of survival in these patients have not previously been studied. METHODS: Doppler color flow mapping and pulsed Doppler techniques were used to obtain hemodynamic measurements of flow in the ascending, transverse and descending aorta, the ductus arteriosus, and across the aortic and mitral valves in infants with critical aortic stenosis. Morphometric measurements of the left heart structures were obtained, and comparisons were made between survivors and nonsurvivors for the hemodynamic and morphometric factors. RESULTS: Twenty-eight infants (mean age 1 +/- .6 days, mean weight 3.6 +/- .6 kg) with critical aortic stenosis were evaluated. Nineteen had a two-ventricle repair initially attempted, and nine had a Norwood operation. Among the patients with a two-ventricle repair, the hemodynamic factors associated with survival after two-ventricle repair included predominant or total antegrade flow in the ascending (p < 0.01) and transverse aorta (p < 0.05). Aortic valve gradient, mitral valve inflow and direction of flow in the ductus arteriosus and descending aorta were unrelated to outcome. The morphometric factors associated with survival after two-ventricle repair included the indexed aortic annulus (p < 0.0002), aortic root (p < 0.003), ascending aorta (p < 0.008) and left ventricular long-axis length (p < 0.01). Left ventricular volume, mass, ejection fraction and mitral valve area were not related to outcome after two-ventricle repair. CONCLUSIONS: In infants with critical aortic stenosis, predominant or total antegrade flow in the ascending and transverse aorta was associated with survival after two-ventricle repair. Determination of a one- versus two-ventricle repair remains a complex issue in infants with critical aortic stenosis. In addition to established morphometric predictors, hemodynamic information on the direction of flow in the aorta may help to define candidates for the Norwood operation.

Aortic Valve Stenosis↗
PubMed1998

Extensive genetic variation revealed in adjacent populations of the schistosome intermediate host Biomphalaria pfeifferi from a single river system.

Random amplified polymorphic DNA (RAPD) analysis was used to study genetic variation among schistosome hosts of the species Biomphalaria pfeifferi. The analysed snails came from 15 sites along a 6-km stretch of a Zimbabwean river, providing data on genetic-geographical relationships over, probably, the smallest scale yet studied for any snail intermediate host species. Only 6% of the DNA fragments were common to all snails, and snail populations as geographically close as 100 m were genetically distinct. The most genetically polymorphic snail populations were those collected within and downstream from human water-contact sites.

Animals↗