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Biomedical subjects

B Good

Publications and source records attributed to B Good.

13 recordsLinked to original sources

Phase-specific gene expression underlying morphological adaptations of the dimorphic human pathogenic fungus, Coccidioides posadasii.

Coccidioides posadasii is a dimorphic fungal pathogen that grows as a filamentous saprobe in the soil and as endosporulating spherules within the host. To identify genes specific to the pathogenic phase of Co. posadasii, we carried out a large-scale study of gene expression in two isolates of the species. From the sequenced Co. posadasii genome, we chose 1,000 open reading frames to construct a 70-mer microarray. RNA was recovered from both isolates at three life-cycle phases: hyphae, presegmented spherules, and spherules releasing endospores. Comparative hybridizations were conducted in a circuit design, permitting comparison between both isolates at all three life-cycle phases, and among all life-cycle phases for each isolate. By using this approach, we identified 92 genes that were differentially expressed between pathogenic and saprobic phases in both fungal isolates, and 43 genes with consistent differential expression between the two parasitic developmental phases. Genes with elevated expression in the pathogenic phases of both isolates included a number of genes that were involved in the response to environmental stress as well as in the metabolism of lipids. The latter observation is in agreement with previous studies demonstrating that spherules contain a higher proportion of lipids than saprobic phase tissue. Intriguingly, we discovered statistically significant and divergent levels of gene expression between the two isolates profiled for 64 genes. The results suggest that incorporating more than one isolate in the experimental design offers a means of categorizing the large collection of candidate genes that transcriptional profiling typically identifies into those that are strain-specific and those that characterize the entire species.

Adaptation, Biological↗

Texel sheep are more resistant to natural nematode challenge than Suffolk sheep based on faecal egg count and nematode burden.

Limited information is available on differences between sheep breeds with respect to helminth resistance under temperate conditions. The present study was designed to confirm and extend preliminary findings on observed breed differences in resistance to naturally acquired gastrointestinal nematodes in Suffolk and Texel sheep. Three trials were carried out. In trial 1 (1999-2003) lambs co-grazed from birth were faecal sampled at various time points up to 17 weeks of age. Worm burden was assessed at 17 weeks of age from a minimum of six lambs per breed in each of the 3 years. In trial 2, faecal egg count (FEC) was determined on six farms with co-grazed Suffolk and Texel purebred lambs. In trial 3 (2001-2003), ewes were faecal sampled at winter housing. In all three trials, an influence of breed on resistance to naturally acquired trichostrongyle infection was demonstrated. In trial 1, significantly higher FEC and worm burden was observed in Suffolk compared with Texel lambs following natural challenge. In trial 2, FEC recorded in lambs from six farms confirmed the breed differences previously observed. A breed difference in resistance to GI parasites was also observed in older ewes. In both breeds, an age effect on the FEC was observed with younger ewes having greater FEC than older ewes.

Age Factors↗

Intron 1 of the interferon gamma gene: Its role in nematode resistance in Suffolk and Texel sheep breeds.

Genetic variation at intron 1 of the interferon gamma gene has recently been associated with variation in faecal egg count in Romney, Merino and Soay breeds of sheep. The Texel breed is more resistant to gastrointestinal nematode infection than the Suffolk breed, based on faecal egg count. Hence, the objective of this experiment was to characterise the polymorphisms of intron 1 of the interferon gammagene in Suffolk and Texel sheep, and to determine if the characterised haplotype variants were associated with faecal egg count variation in these breeds. Intron 1 haplotypes and faecal egg measurements were determined for Suffolks (n=113) and Texels (n=135). Four haplotypes were identified in Suffolks (A, B, C and D), two haplotypes as previously described, and two previously unknown haplotypes. However, there was no association between interferon gamma intron 1 haplotype and faecal egg count in Suffolks. In contrast, two previously identified haplotypes (A and B) were present in the Texel breed, and the B haplotype was associated with resistance to nematode infection (P=0.02). These results suggest that intron 1 of the interferon gamma gene has an important role in resistance to nematode infection in the Texel breed.

Animals↗

Major histocompatibility complex DRB1 gene: its role in nematode resistance in Suffolk and Texel sheep breeds.

A potential control strategy for nematode infection in sheep is the implementation of a breeding programme to select for genes associated with resistance. The Texel breed is more resistant to gastrointestinal nematode infection than the Suffolk breed, based on faecal egg count, and this difference should enable the identification of some of the genes responsible for resistance. The objective of this study was to determine if variation at the ovine MHC-DRB1 locus was associated with variation in faecal egg count in Suffolk and Texel sheep. Ovar-DRB1 alleles and faecal egg count were determined for Texel (n = 105) and Suffolk (n = 71) lambs. Eight Ovar-DRB1 alleles, including 1 previously unknown allele, were identified in the Texel breed by sequence-base-typing. Seven Ovar-DRB1 alleles were identified in the Suffolk breed. Two Ovar-DRB1 alleles were common to both breeds, but were among the least frequent in the Suffolk population. In the Suffolk breed 1 Ovar-DRB1 allele was associated with a decrease in faecal egg count and 2 alleles with an increase in faecal egg count. This locus accounted for 14% of the natural variation in faecal egg count in Suffolks. There was no evidence for an association between Ovar-DRB1 alleles and faecal egg count in the Texel breed and the Ovar-DRB1 locus accounted for only 3% of the phenotypic variation in faecal egg count. These results suggest that the Ovar-DRB1 gene plays an important role in resistance to nematode infection in the Suffolk breed. The difference in faecal egg counts between these breeds may be attributable in part to the different allele profile at the Ovar-DRB1 locus.

Alleles↗

Genetic composition of human immunodeficiency virus type 1 in cerebrospinal fluid and blood without treatment and during failing antiretroviral therapy.

Human immunodeficiency virus (HIV) infection of the central nervous system (CNS) is a significant cause of morbidity. The requirements for HIV adaptation to the CNS for neuropathogenesis and the value of CSF virus as a surrogate for virus activity in brain parenchyma are not well established. We studied 18 HIV-infected subjects, most with advanced immunodeficiency and some neurocognitive impairment but none with evidence of opportunistic infection or malignancy of the CNS. Clonal sequences of C2-V3 env and population sequences of pol from HIV RNA in cerebrospinal fluid (CSF) and plasma were correlated with clinical and virologic variables. Most (14 of 18) subjects had partitioning of C2-V3 sequences according to compartment, and 9 of 13 subjects with drug resistance exhibited discordant resistance patterns between the two compartments. Regression analyses identified three to seven positions in C2-V3 that discriminated CSF from plasma HIV. The presence of compartmental differences at one or more of the identified positions in C2-V3 was highly associated with the presence of discordant resistance (P = 0.007), reflecting the autonomous replication of HIV and the independent evolution of drug resistance in the CNS. Discordance of resistance was associated with severity of neurocognitive deficits (P = 0.07), while low nadir CD4 counts were linked both to the severity of neurocognitive deficits and to discordant resistance patterns (P = 0.05 and 0.09, respectively). These observations support the study of CSF HIV as an accessible surrogate for HIV virions in the brain, confirm the high frequency of discordant resistance in subjects with advanced disease in the absence of opportunistic infection or malignancy of the CNS, and begin to identify genetic patterns in HIV env associated with adaptation to the CNS.

AIDS Dementia Complex↗

Ocular toxocariasis in schoolchildren.

Ocular toxocariasis in humans is typically a unilateral disease caused by second-stage larvae of the Toxocara species. Serological evidence of widespread infection in humans provides little information on clinical disease. There is only a single previous estimate of the prevalence of ocular toxocariasis (from Alabama). The present survey examined the extent of consultant-diagnosed toxocaral eye disease among a population of schoolchildren. More than 120,000 participants were surveyed by questionnaire and follow-up. Two sets of control subjects from the same school and from the same county were compared with persons who had ocular toxocariasis. The prevalence of consultant-diagnosed toxocaral eye disease was 6.6 cases per 100,000 persons when only cases regarded as definite by the consultant ophthalmologist were included. This increased to 9.7 cases per 100,000 persons when both definite and strongly suspected cases were included. Geophagia and a history of convulsion were associated with toxocaral eye disease in both of the case-control studies.

Adolescent↗

Improving access to mammograms through community-based influenza clinics. A quasi-experimental study.

BACKGROUND: It is a national priority to increase breast-cancer screening among women aged > or = 50. Annual influenza clinics may represent an efficient setting in which to promote breast-cancer screening among older women. To our knowledge, this possibility has not previously been explored. OBJECTIVE: To examine whether offering women attending community-based influenza clinics the opportunity to receive a scheduling telephone call from a mammography facility will result in an increase in the number of mammograms performed over a 6-month period. METHODS: We used a quasi-experimental design with 6-month follow-up. A contemporaneous population-based survey provided a further control group for comparison. The sample group consisted of a total of 284 women attending nine community-based influenza clinics in a semirural county in Connecticut. All women were aged > or = 50 and reported no mammogram in the preceding 12 months. All women received informational literature on mammography. Experimental subjects were each asked if a radiology facility chosen by the subject could call her at home to schedule a mammogram. Mammograms performed were determined by hospital record for participants who received a scheduling call from a radiology facility, and by self-report for all other participants. RESULTS: Mammography use following access through influenza clinics was approximately twice that of women attending influenza clinics where access to mammography was not offered. Using three different assumptions regarding participants whose mammography status was unknown, the relative risks ranged between 1.6 and 2.1. For each assumption the results were statistically significant (chi(2)=8.51-12.2; p<0.001). CONCLUSIONS: Linking access to mammography at community-based influenza clinics can significantly increase the use of mammograms among women aged > or = 50. Further studies should seek to confirm these findings and determine the degree to which they can be replicated in a variety of communities. Enhancing preventive health practice through the bundling of services suggests a new strategy to exploit available interventions to improve health.

Community Health Services↗

The influence of inoculum size and time post-infection on the number and position of Toxocara canis larvae recovered from the brains of outbred CD1 mice.

Outbred CD1 mice were administered doses of 1000 and 3000 Toxocara canis eggs and postmortem took place on days 7, 42 and 120 post-infection. Mice were killed by cervical dislocation and brains were sagitally bisected and fixed in 10% neutral buffered formalin prior to histological preparation and examination. The number of T. canis larvae were counted per brain and per section and the number of larvae cited for the first time per section were also recorded. These observations were compared by dose administered and by day of postmortem. The total number of larvae per brain and per section was higher for the 3000 dose compared to the 1000 dose. A different pattern emerged for the number of larvae observed in the brain over the three postmortem days depending upon the dose received. For the 1000 dose larval numbers increase from day 7 to day 120 whereas for the 3000 dose the opposite trend occurs. Larvae were assigned to one of five regions in the brain - the telencephalon, diencephalon, cerebellum, medulla, pons and brain stem and the olfactory bulb. Larvae did not show a random distribution in the brain. The majority of larvae were recorded from the telencephalon and the cerebellum. The percentage of sections with larvae in them is higher for the 3000 dose compared to the 1000 dose for all regions of the brain. For the majority of regions, the percentage of sections with larvae in them increases between day 7 and 42 and then decreases by day 120 and this is most pronounced for the cerebellum. For the telencephalon and diencephalon only, more larvae were detected on the right hand side of the brain compared to the left hand side. Statistical analysis revealed that dose and brain region are significant factors which influence the number of larvae observed in histological sections of the brain but day post-infection is not.

Analysis of Variance↗

Preliminary studies of mineralization during distraction osteogenesis.

Distraction osteogenesis by the Ilizarov method was performed on 20 dogs. Mineralization at the site of the left tibial metaphyseal lengthening was measured by weekly quantitative computer tomography (QCT) using the contralateral tibia as a control. Four dogs each were killed on Days 7, 14, 21, and 28 of distraction in order to correlate QCT with microradiology, nondecalcified histology, quantitative calcium analysis, and scanning electron microscopy. It was consistently found that intramembranous ossification proceeded centripetally from each corticotomy surface toward the central fibrous interzone. Bone columns crystallized along longitudinally oriented collagen bundles, expanding circumferentially to surrounding bundles. As the distraction gap increased, the bone columns increased in length and in diameter, while the fibrous interzone remained about 4 mm long. Histologically, the bone columns resembled stalagmites and stalactites, as seen by microradiography and scanning electron microscopy, that projected from each corticotomy surface toward the center. These cones reached maximum diameters of 150-200 mu at the corticotomy surfaces. Radiodensity (QCT) increased gradually from the central fibrous interzone toward each corticotomy surface. Mineral density, as determined by calcium quantification, reflected the microscopic geometry and radiographic polarity.

Animals↗

Storage phosphor radiographs vs conventional films: interpreters' perceptions of diagnostic quality.

We compared storage phosphor images with high-quality conventional film-screen images by evaluating physicians' perceptions of image quality and their levels of confidence in making diagnostic interpretations. Eight physicians each examined 11 posteroanterior storage phosphor chest images (obtained with an experimental high-resolution storage phosphor system) side by side with conventional film images of the same patients. The storage phosphor images were obtained only minutes after the conventional radiographs were obtained. Storage phosphor images were digitally printed onto films in two different formats: a full-size (12 X 14 in. [30.5 X 35.6 cm]) and a half-size format of four computer-processed, minified images (6 X 7 in. [15.2 X 17.8 cm] each). Most of the responses rated the quality and resolution/sharpness of conventional images, as well as their ability to display the complete lung field, as either "excellent" or "good"; however, the storage phosphor images received significantly better ratings (p less than .05). Computer-processed minified versions of the storage phosphor images also received better ratings than did the conventional images. When the physicians were asked to rate their confidence level in making diagnoses with each of the two techniques, in 74 of 88 cases they indicated that their level of confidence would be at least as high when using the storage phosphor images as when using the conventional images.

Humans↗

Culture, illness, and care: clinical lessons from anthropologic and cross-cultural research.

Major health care problems such as patient dissatisfaction, inequity of access to care, and spiraling costs no longer seem amenable to traditional biomedical solutions. Concepts derived from anthropologic and cross-cultural research may provide an alternative framework for identifying issues that require resolution. A limited set of such concepts is described as illustrated, including a fundamental distinction between disease and illness, and the notion of the cultural construction of clinical reality. These social science concepts can be developed into clinical strategies with direct application in practice and teaching. One such strategy is outlined as an example of a clinical social science capable of translating concepts from cultural anthropology into clinical language for practical application. The implementation of this approach in medical teaching and practice requires more support, both curricular and financial.

Adult↗