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Biomedical subjects

J B Anderson

Publications and source records attributed to J B Anderson.

At least 19 recordsLinked to original sources

Broadcasts of wing-fanning vibrations recorded from calling male Ceratitis capitata (Diptera: Tephritidae) increase captures of females in traps.

Female Mediterranean fruit flies, Ceratitis capitata (Wiedemann), from the sterile-male rearing facility in El Pino, Guatemala, were exposed to broadcasts of wing-fanning vibrations recorded from males engaged in calling behavior to investigate the feasibility of developing a female-selective acoustic trap. The recorded signals had frequent amplitude fluctuations and peak frequencies approximately 350 Hz, typical of signals observed in previous studies of Mediterranean fruit fly acoustic behavior. Females did not exhibit long-distance phonotaxis, but remained near a speaker significantly longer when the sounds were broadcast at 103-107 dB than when the speaker was silent. In addition, significantly higher percentages of females were captured by yellow adhesive traps next to a broadcasting speaker than by traps next to a silent mimic. Additional bioassays were conducted with synthetic, 350-Hz tones produced by a thermoacoustic tube as well as with silent mimics of the different sound sources to examine the relative responsiveness of female Mediterranean fruit flies to traps with different acoustic and visual features. The visual attributes of the different sound source assemblies significantly affected capture rates. The range over which the broadcast significantly increased the percentage of female captures was <0.5 m, which may limit the utility of these acoustic cues in large-scale trapping programs. However, the findings of this study do justify further testing of whether optimized short-range acoustic signals could be used to augment longer range pheromonal and visual cues to improve the efficacy of female-selective traps.

Acoustics↗

Acoustic detection of termite infestations in urban trees.

A portable, low-frequency acoustic system was used to detect termite infestations in urban trees. The likelihood of infestation was rated independently by a computer program and an experienced listener that distinguished insect sounds from background noises. Because soil is a good insulator, termite sounds could be detected easily underneath infested trees, despite the presence of high urban background noise. Termite sounds could be detected also in trunks, but background noise often made it difficult to identify termite signals unambiguously. High likelihoods of termite infestation were predicted at four live oak (Quercus virginiana Mill, Fagacae), two loblolly pine (Pinus taeda L., Pinacae), and two baldcypress (Taxodium distichum Rich. Pinacae) trees that wood-baited traps had identified as infested with Coptotermes formosanus Shiraki. Infestations also were predicted at two pine trees with confirmed recoveries of Reticulitermes flavipes (Kollar). Low likelihoods of infestation were predicted in four oak trees where no termites were found. Additional tests were conducted in anechoic environments to determine the range of acoustic detectability and the feasibility of acoustically estimating termite population levels. There was a significant regression between the activity rate and the number of termites present in a wood trap block, with a minimum detectable number of approximately 50 workers per liter of wood. The success of these field tests suggests that currently available acoustic systems have considerable potential to detect and monitor hidden infestations of termites in urban trees and around building perimeters in addition to their present uses to detect and monitor termite infestations in buildings.

Acoustics↗

Divergence in fitness and evolution of drug resistance in experimental populations of Candida albicans.

The dissemination and persistence of drug-resistant organisms in nature depends on the relative fitness of sensitive and resistant genotypes. While resistant genotypes are expected to be at an advantage compared to less resistant genotypes in the presence of drug, resistance may incur a cost; resistant genotypes may be at a disadvantage in the absence of drug. We measured the fitness of replicate experimental populations of the pathogenic yeast Candida albicans founded from a single progenitor cell in a previous study (L. E. Cowen, D. Sanglard, D. Calabrese, C. Sirjusingh, J. B. Anderson, and L. M. Kohn, J. Bacteriol. 182:1515-1522, 2000) and evolved in the presence, and in the absence, of the antifungal agent fluconazole. Fitness was measured both in the presence and in the absence of fluconazole by placing each evolved population in direct competition with the drug-sensitive ancestor and measuring the reproductive output of each competitor in the mixture. Populations evolved in the presence of drug diverged in fitness. Any significant cost of resistance, indicated by reduced fitness in the absence of drug, was eliminated with further evolution. Populations evolved in the absence of drug showed more uniform increases in fitness under both conditions. Fitness in the competition assays was not predicted by measurements of the MICs, doubling times, or stationary-phase cell densities of the competitors in isolation, suggesting the importance of interactions between mixed genotypes in competitions.

Antifungal Agents↗

Infrequent genetic exchange and recombination in the mitochondrial genome of Candida albicans.

Previous analyses of diploid nuclear genotypes have concluded that recombination has occurred in populations of the yeast Candida albicans. To address the possibilities of clonality and recombination in an effectively haploid genome, we sequenced seven regions of mitochondrial DNA (mtDNA) in 45 strains of C. albicans from human immunodeficiency virus-positive patients in Toronto, Canada, and 3 standard reference isolates of C. albicans, CA, CAI4, and WO-1. Among a total of 2,553 nucleotides in the seven regions, 62 polymorphic nucleotide sites and seven indels defined nine distinct mtDNA haplotypes among the 48 strains. Five of these haplotypes occurred in more than one strain, indicating clonal proliferation of mtDNA. Phylogenetic analysis of mtDNA haplotypes resulted in one most-parsimonious tree. Most of the nucleotide sites undergoing parallel change in this tree were clustered in blocks that corresponded to sequenced regions. Because of the existence of these blocks, the apparent homoplasy can be attributed to infrequent, past genetic exchange and recombination between individuals and cannot be attributed to parallel mutation. Among strains sharing the same mtDNA haplotypes, multilocus nuclear genotypes were more similar than expected from a random comparison of nuclear DNA genotypes, suggesting that clonal proliferation of the mitochondrial genome was accompanied by clonal proliferation of the nuclear genome.

Base Sequence↗

Multilocus genotyping indicates that the ability to invade the bloodstream is widespread among Candida albicans isolates.

Multilocus genotyping was used to compare populations of Candida albicans from oral mucosa and blood. No significant differences in allele frequencies between the two samples were detected, and in a dendrogram of genotypic similarities, genotypes from both types of samples were finely interspersed. This is evidence for widespread distribution of invasive potential.

Candida albicans↗

The progression of benign prostatic hyperplasia: examining the evidence and determining the risk.

BACKGROUND: Benign prostatic hyperplasia (BPH) is often associated with enlargement of the prostate gland, lower urinary tract symptoms, decreased urinary flow and a reduced quality of life. Furthermore, if the symptoms associated with BPH are left untreated, serious complications, such as acute urinary retention, may ensue. Evidence is emerging from long-term clinical studies to suggest that BPH is a progressive disease, with some patients progressing much more rapidly than others. OBJECTIVE: This article aims to explore the natural history of BPH progression from a molecular, pathological and clinical perspective, with emphasis on the key clinical evidence to support the progressive nature of this disease. How our increased understanding of the disease and of the risk factors for BPH progression might be applied to improve current management practices are also discussed. CONCLUSION: Strategies to identify patients most at risk and guidelines directed towards long-term management, in addition to short-term treatment, may be useful in helping to prevent BPH progression.

Disease Progression↗

Identification and analysis of the myosin superfamily in Drosophila: a database approach.

The recent sequencing of the genome of Drosophila melanogaster has provided a valuable resource for mining the database for genes of interest. We took advantage of this opportunity in an attempt to identify novel myosins in Drosophila and confirm the presence of the previously identified myosins from classes I, II, III, V, VI, and VII. The Drosophila database annotators predicted the structure of three additional proteins which we identified as novel unconventional myosins, two of which fell into classes XV and XVIII, respectively. Our own efforts predicted the presence of four additional partial sequences that appear to be myosin proteins which did not fall into any specific class. In the future comparative genomics will hopefully lead to the placement of these myosins into new classes.

Animals↗

Absence of perilipin results in leanness and reverses obesity in Lepr(db/db) mice.

Obesity is a disorder of energy balance. Hormone-sensitive lipase (HSL) mediates the hydrolysis of triacylglycerol, the major form of stored energy in the body. Perilipin (encoded by the gene Plin), an adipocyte protein, has been postulated to modulate HSL activity. We show here that targeted disruption of Plin results in healthy mice that have constitutively activated fat-cell HSL. Plin -/- mice consume more food than control mice, but have normal body weight. They are much leaner and more muscular than controls, have 62% smaller white adipocytes, show elevated basal lipolysis that is resistant to beta-adrenergic agonist stimulation, and are cold-sensitive except when fed. They are also resistant to diet-induced obesity. Breeding the Plin -/- alleles into Leprdb/db mice reverses the obesity by ncreasing the metabolic rate of the mice. Our results demonstrate a role for perilipin in reining in basal HSL activity and regulating lipolysis and energy balance; thus, agents that inactivate perilipin may prove useful as anti-obesity medications.

Adipose Tissue↗

The changing pattern of mortality and morbidity from radical cystectomy.

OBJECTIVES: To examine the morbidity and mortality of radical cystectomy as currently practised, and to compare the findings with historical data. PATIENTS AND METHODS: The operative mortality and early and late complications were recorded in 101 consecutive patients (median age 65 years, range 38-81; 33 aged >70 years) undergoing radical cystectomy between April 1992 and October 1997. Fifteen patients had relapsed after previous radical radiotherapy. RESULTS: The median postoperative stay was 14 days (range 8-44). There were two deaths within 60 days of surgery (of patients aged 46 and 59 years) from respiratory failure and sepsis, respectively. The mortality in the elderly was not more than in other age groups. The early morbidity included two cases of lower limb insufficiency, both in the salvage cystectomy group, where the morbidity was significantly higher than in those undergoing primary cystectomy (chi-squared, P<0.01). Three patients underwent early re-exploration. There were four clinically significant episodes of deep vein thrombosis and two pulmonary emboli that were not fatal. CONCLUSION: As currently practised, radical cystectomy is associated with a lower mortality (<2%) and morbidity than described previously. The added morbidity of salvage cystectomy and the acceptable mortality of primary cystectomy suggests that the treatment of choice for muscle-invasive disease is primary cystectomy, with external beam radiotherapy reserved for those patients unfit for major surgical intervention. Age alone should no longer be considered a contraindication to cystectomy.

Adult↗

Computational flow study of the continuous flow ventricular assist device, prototype number 3 blood pump.

A computational fluid dynamics study of blood flow in the continuous flow ventricular assist device, Prototype No. 3 (CFVAD3), which consists of a 4 blade shrouded impeller fully supported in magnetic bearings, was performed. This study focused on the regions within the pump where return flow occurs to the pump inlet, and where potentially damaging shear stresses and flow stagnation might occur: the impeller blade passages and the narrow gap clearance regions between the impeller-rotor and pump housing. Two separate geometry models define the spacing between the pump housing and the impeller's hub and shroud, and a third geometry model defines the pump's impeller and curved blades. The flow fields in these regions were calculated for various operating conditions of the pump. Pump performance curves were calculated, which compare well with experimentally obtained data. For all pump operating conditions, the flow rates within the gap regions were predicted to be toward the inlet of the pump, thus recirculating a portion of the impeller flow. Two smaller gap clearance regions were numerically examined to reduce the recirculation and to improve pump efficiency. The computational and geometry models will be used in future studies of a smaller pump to determine increased pump efficiency and the risk of hemolysis due to shear stress, and to insure the washing of blood through the clearance regions to prevent thrombosis.

Computer Simulation↗

Evolution of drug resistance in experimental populations of Candida albicans.

Adaptation to inhibitory concentrations of the antifungal agent fluconazole was monitored in replicated experimental populations founded from a single, drug-sensitive cell of the yeast Candida albicans and reared over 330 generations. The concentration of fluconazole was maintained at twice the MIC in six populations; no fluconazole was added to another six populations. All six replicate populations grown with fluconazole adapted to the presence of drug as indicated by an increase in MIC; none of the six populations grown without fluconazole showed any change in MIC. In all populations evolved with drug, increased fluconazole resistance was accompanied by increased resistance to ketoconazole and itraconazole; these populations contained ergosterol in their cell membranes and were amphotericin sensitive. The increase in fluconazole MIC in the six populations evolved with drug followed different trajectories, and these populations achieved different levels of resistance, with distinct overexpression patterns of four genes involved in azole resistance: the ATP-binding cassette transporter genes, CDR1 and CDR2; the gene encoding the target enzyme of the azoles in the ergosterol biosynthetic pathway, ERG11; and the major facilitator gene, MDR1. Selective sweeps in these populations were accompanied by additional genomic changes with no known relationship to drug resistance: loss of heterozygosity in two of the five marker genes assayed and alterations in DNA fingerprints and electrophoretic karyotypes. These results show that chance, in the form of mutations that confer an adaptive advantage, is a determinant in the evolution of azole drug resistance in experimental populations of C. albicans.

AIDS-Related Opportunistic Infections↗

Monte Carlo methods in electronic structures for large systems.

Quantum Monte Carlo methods have recently made it possible to calculate the electronic structure of relatively large molecular systems with very high accuracy. These large systems range from positron complexes [NH(2),Ps] with approximately 10 electrons to C(20) isomers with 120 electrons, to silicon crystal structures of 250 atoms and 1000 valence electrons. The techniques for such calculations and a sampling of applications are reviewed.

Journal Article↗

Baclofen increases the soleus stretch reflex threshold in the early swing phase during walking in spastic multiple sclerosis patients.

The effect of baclofen on walking performance was examined in nine spastic multiple sclerosis patients. In addition, nine healthy subjects were tested as controls. The modulation of the short latency soleus stretch reflex was closer to normal with baclofen compared to the recordings without baclofen, the modulation index being 74% (range: 60 - 100) with baclofen and 62% (range: 20 - 100) without baclofen, P=0.03. In healthy subjects the modulation index was 100% (range: 52 - 100). In the early swing phase the threshold of the soleus stretch reflex was significantly higher during baclofen medication being 139 deg/s (range: 63 - 302) compared with 93 deg/s (range: 37 - 187) without baclofen, P=0.004. The relation between the stretch velocity (input) and the amplitude of the stretch reflex (output) in early swing phase was unchanged being 0. 27 microVs/deg (range: 0.1 - 1.51) in patients with baclofen and 0. 24 microVs/deg (range: 0.08 - 0.79) without baclofen, P=0.25. Baclofen induced no change in input - output properties of the stretch reflex during walking compared with findings in a sitting position at matched EMG activity. There was a significant correlation between clinical spasticity score and stretch reflex threshold in the early swing phase (rho=-0.61, P=0.04) and between clinical spasticity score and the slope of the best linear fit in the early swing phase (rho=0.72, P=0.009).

Adult↗

Follicular lymphoma can be distinguished from benign follicular hyperplasia by flow cytometry using simultaneous staining of cytoplasmic bcl-2 and cell surface CD20.

The distinction between benign follicular hyperplasia (FH) and follicular lymphoma (FL) is sometimes problematic. We wanted to determine whether the expression of bcl-2 of FH was quantitatively different from that of FL, using surface CD20 expression as a discriminator of the various lymphoid compartments. Lymph node cell suspensions from 12 cases of FH and 17 cases of FL were analyzed by flow cytometry using a combined surface CD20 and intracellular bcl-2 staining. CD20- T cells in FH demonstrated the same bcl-2 expression as the CD20+ mantle cells, but the bright CD20+ germinal center cells showed near absence of bcl-2 expression. In contrast, the neoplastic cells of FL showed greater bcl-2 expression than the T cells of the same tumors and all cell populations of FH. This difference was particularly significant between the neoplastic B cells of FL and the germinal center cells of FH. The combined analysis of CD20 and bcl-2 should be useful for the differential diagnosis between FH and FL and particularly applicable to limited samples or when B-cell clonality is in question. Whether the quantitation of bcl-2 expression can be of further discriminatory value in malignant lymphomas remains to be determined.

Antibodies, Monoclonal↗

Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of followup.

PURPOSE: Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide monotherapy or castration. MATERIALS AND METHODS: Data from 2 open label, multicenter studies of identical design were pooled according to protocol. Patients with stage T3/4 prostate cancer were randomized to receive 150 mg. bicalutamide daily or castration (orchiectomy or 3.6 mg. goserelin acetate every 28 days) in a 2:1 ratio. RESULTS: A total of 480 patients with locally advanced prostate cancer were randomized to treatment. After a median followup of 6.3 years mortality was 56%. There was no statistically significant difference between the 2 groups in overall survival (hazard ratio 1.05, upper 1-sided 95% confidence limit 1.31, p = 0.70) or time to progression (1.20, 1.45, p = 0.11). There were statistically significant benefits in the bicalutamide monotherapy group in the 2 quality of life parameters of sexual interest (p = 0.029) and physical capacity (p = 0.046). The highest incidences of adverse events were the pharmacological side effects of hot flashes in the castration group, and breast pain and gynecomastia in the bicalutamide group. The incidences of other types of adverse events were low. Bicalutamide was well tolerated, with few drug related withdrawals from study, and no new safety issues were identified during this longer followup. CONCLUSIONS: Monotherapy with 150 mg. bicalutamide is an attractive alternative to castration in patients with locally advanced prostate cancer for whom immediate hormone therapy is indicated.

Androgen Antagonists↗