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Biomedical subjects

Richard Fox

Publications and source records attributed to Richard Fox.

At least 19 recordsLinked to original sources
PubMed2006

Species richness changes lag behind climate change.

Species-energy theory indicates that recent climate warming should have driven increases in species richness in cool and species-poor parts of the Northern Hemisphere. We confirm that the average species richness of British butterflies has increased since 1970-82, but much more slowly than predicted from changes of climate: on average, only one-third of the predicted increase has taken place. The resultant species assemblages are increasingly dominated by generalist species that were able to respond quickly. The time lag is confirmed by the successful introduction of many species to climatically suitable areas beyond their ranges. Our results imply that it may be decades or centuries before the species richness and composition of biological communities adjusts to the current climate.

Animal Migration↗
PubMed2006

Oral chlorambucil for extranodal, marginal zone, B-cell lymphoma of mucosa-associated lymphoid tissue of the orbit.

PURPOSE: To report the outcome of oral chlorambucil as a single treatment in patients with orbital mucosa-associated lymphoid tissue (MALT) lymphoma. DESIGN: Retrospective nonrandomized clinical study. PARTICIPANTS: Thirty-three patients with isolated orbital MALT lymphoma. METHODS: Medical records of all patients with histology-verified orbital MALT lymphoma treated with oral chlorambucil at the Royal Melbourne Hospital were reviewed. MAIN OUTCOME MEASURES: Complete clinical response, partial response, local relapse, systemic extension (distant relapse), and survival. RESULTS: Thirty-three patients (19 female; mean age, 69 years) participated in the study. Patients received an average of 4 courses of oral chlorambucil with a mean total dose of 600 mg. The lacrimal gland was the most frequent site of occurrence (24%), followed by the conjunctiva, eyelid, and superior orbit. Orbital mass, swelling, and diplopia were common presenting signs. Complete response was noted in 26 patients (79%). In 2 of the patients with complete clinical response, mild residual thickening was noted on follow-up orbital imaging studies. Four patients (12%) showed disease recurrence or relapse. Mean follow-up time was 32 (+/-20) months (range, 8 months-6 years; median, 26 months). None of the patients developed granulocytopenia secondary to chemotherapy, and none suffered significant nausea or vomiting. One patient with malignant transformation died 12 months after diagnosis and initial treatment. CONCLUSIONS: Systemic chemotherapy with chlorambucil is a reasonable option in patients with orbital MALT lymphoma. It is associated with minimal to no side effects. Additionally, it may be well tolerated by elderly patients and also may treat subclinical disease elsewhere.

Administration, Oral↗
PubMed2006

Confidence in spine training among senior neurosurgical and orthopedic residents.

STUDY DESIGN: A cross-sectional survey of senior neurosurgical and orthopedic residents. OBJECTIVE: To evaluate the confidence of senior orthopedic and neurosurgery residents in performing spinal surgical procedures and their need for further training. The content and exposure to spine training as well as anticipated practice profile were characterized. SUMMARY OF BACKGROUND DATA: Spinal surgery is performed by specialists with backgrounds in orthopedic surgery and neurosurgery. As this subspecialty evolves, the need to modify training programs to keep up with technological and medical advances becomes increasingly clear. The primary objective of this study was to evaluate the self-assessed confidence and perceived need for further training of senior orthopedic and neurosurgical residents in performing a number of spinal surgical procedures. METHODS: An evaluation of self-assessed surgical competence of senior orthopedic and neurosurgery residents in Canada was undertaken by mail-out questionnaire. A follow-up questionnaire was mailed to nonresponders 3 months later. Survey results were summarized using SPSS statistical software, and descriptive and comparative analyses were performed. RESULTS: Significant differences in time and exposure to spine training differentiated the neurosurgical and orthopedic residencies (37% and 16% of total residency time devoted to spine, respectively). Neurosurgical residents reported significantly higher levels of confidence for all 25 surgical procedures. Of those residents anticipating incorporating spine into their practice, 29% of neurosurgery residents planned on entering a spine fellowship compared with 17% of their orthopedic colleagues. CONCLUSIONS: Training in spine surgery constitutes a considerably larger proportion of neurosurgery residency than orthopedic residency. Neurosurgery residents graduate with significantly higher levels of confidence to perform spine surgery, while orthopedic residents report significantly higher need for additional training in spine surgery. The majority of neurosurgery graduates report that they will include spine in their clinical practice, while most orthopedic graduates will exclude it.

Cross-Sectional Studies↗
PubMed2005

Prioritizing multiple-use landscapes for conservation: methods for large multi-species planning problems.

Across large parts of the world, wildlife has to coexist with human activity in highly modified and fragmented landscapes. Combining concepts from population viability analysis and spatial reserve design, this study develops efficient quantitative methods for identifying conservation core areas at large, even national or continental scales. The proposed methods emphasize long-term population persistence, are applicable to both fragmented and natural landscape structures, and produce a hierarchical zonation of regional conservation priority. The methods are applied to both observational data for threatened butterflies at the scale of Britain and modelled probability of occurrence surfaces for indicator species in part of Australia. In both cases, priority landscapes important for conservation management are identified.

Algorithms↗
PubMed2005

Directed molecular evolution by machine learning and the influence of nonlinear interactions.

Alternative search strategies for the directed evolution of proteins are presented and compared with each other. In particular, two different machine learning strategies based on partial least-squares regression are developed: the first contains only linear terms that represent a given residue's independent contribution to fitness, the second contains additional nonlinear terms to account for potential epistatic coupling between residues. The nonlinear modeling strategy is further divided into two types, one that contains all possible nonlinear terms and another that makes use of a genetic algorithm to select a subset of important interaction terms. The performance of each modeling type as a function of training set size is analysed. Simulated molecular evolution on a synthetic protein landscape shows the use of machine learning techniques to guide library design can be a powerful addition to library generation methods such as DNA shuffling.

Algorithms↗
PubMed2005

Semi-synthetic DNA shuffling of aveC leads to improved industrial scale production of doramectin by Streptomyces avermitilis.

The avermectin analog doramectin (CHC-B1), sold commercially as Dectomax, is biosynthesized by Streptomyces avermitilis. aveC, a gene encoding an unknown mechanistic function, plays an essential role in the production of doramectin (avermectin CHC-B1), modulating the production ratio of CHC-B1 to other avermectins, most notably the undesirable analog CHC-B2. To improve the production ratio for doramectin, the aveC gene was subjected to iterative rounds of semi-synthetic DNA shuffling. Libraries of shuffled aveC gene variants were transformed into S. avermitilis, screened using a miniaturized 96-well growth and production format, and analyzed by high throughput mass spectrometry to determine CHC-B2:CHC-B1 ratios. Several improved aveC variants were identified; the best shuffled gene encoded 10 amino acid mutations, and conferred a final CHC-B2:CHC-B1 ratio of 0.07:1, a 23-fold improvement over the starting gene (aveC wild type). Chromosomal insertion of an improved aveC shuffled gene into a high titer S. avermitilis strain yielded an improved doramectin production strain. This strain is under development to be used commercially, and is expected to provide considerable cost savings in large-scale manufacture, as well as significantly reducing by-product levels of CHC-B2 requiring disposal.

DNA Shuffling↗
PubMed2005

Surgical biopsy in lymphoma.

The term 'lymphoma' describes malignant lymphoproliferative diseases that originate from B- and T-cells in the lymphatic system. The majority of lymphomas arise from lymph nodes, while some may originate in extranodal sites. Lymphoma is a common cancer, affecting approximately 4000 people in Australia per year, and constituting 4% of newly diagnosed cancers. Lymphoma is primarily a disease of adults, and is the sixth most common cancer in men, after prostate, colorectal, lung, melanoma and bladder, and the fifth most common cancer in women, after breast, colorectal, melanoma and lung.

Biopsy↗
PubMed2004

Spatial patterns in species distributions reveal biodiversity change.

Interpretation of global biodiversity change is hampered by a lack of information on the historical status of most species in most parts of the world. Here we show that declines and increases can be deduced from current species distributions alone, using spatial patterns of occupancy combined with distribution size. Declining species show sparse, fragmented distributions for their distribution size, reflecting the extinction process; expanding species show denser, more aggregated distributions, reflecting colonization. Past distribution size changes for British butterflies were deduced successfully from current distributions, and former distributions had some power to predict future change. What is more, the relationship between distribution pattern and change in British butterflies independently predicted distribution change for butterfly species in Flanders, Belgium, and distribution change in British rare plant species is similarly related to spatial distribution pattern. This link between current distribution patterns and processes of distribution change could be used to assess relative levels of threat facing different species, even for regions and taxa lacking detailed historical and ecological information.

Animals↗
PubMed2004

Heparin-binding epidermal growth factor-like growth factor links hepatocyte priming with cell cycle progression during liver regeneration.

The mechanisms that regulate the transition between the initial priming phase and DNA replication in liver regeneration are poorly understood. To study this transition, we compared events occurring after standard two-thirds partial hepatectomy, which elicits full regeneration, with response to a reduced hepatectomy, one-third partial hepatectomy (1/3PH), which leads to little DNA replication. Although the initial response to partial hepatectomy at the priming phase appeared to be similar between the two procedures, cell cycle progression was significantly blunted in 1/3PH mice. Among the main defects observed in 1/3PH mice were an almost complete deficiency in retinoblastoma phosphorylation and the lack of increase in kinase activity associated with cyclin E. We report that, in two-thirds partial hepatectomy mice, the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) preceded the start of DNA replication and was not detectable in 1/3PH animals. Injection of HB-EGF into 1/3PH mice resulted in a >15-fold increase in DNA replication. Moreover, we show that hepatocyte DNA replication was delayed in HB-EGF knock-out mice. In summary, we show that HB-EGF is a key factor for hepatocyte progression through G(1)/S transition during liver regeneration.

Animals↗
PubMed2004

Appendicular arterial tumor embolization in two cats with pulmonary carcinoma.

A 13-year-old neutered male Persian cat and an 11-year-old neutered female Persian cat were examined because of an acute onset of lameness. In both cats, conscious proprioception and reflexes were diminished in the affected limb. In 1 cat, no blood flow was detected in the left brachial artery with a Doppler ultrasonic flow detector, whereas blood flow in the right brachial artery was easily documented. In the other cat, the right femoral pulse was not palpable. Neither cat had any echocardiographic evidence of cardiac disease. In both cats, treatment was primarily supportive. One cat died, and the other was euthanatized. At necropsy, lung lobe consolidation was seen. Microscopically, there was multifocal infiltration of the lung parenchyma with cuboidal to columnar neoplastic epithelial cells. Neoplastic epithelial cells of similar morphology were identified in nodular masses in sections of muscle, and intravascular tumor emboli were identified obliterating small and large arterioles. Immunohistochemical staining of pulmonary and muscular tissue for pan-cytokeratin antigen revealed intense cytoplasmic staining of neoplastic cells. Staining for factor VIII-related antigen confirmed that clusters of neoplastic cells represented intravascular emboli. Clinical signs in the cats were attributed to arterial occlusion by tumor emboli.

Animals↗
PubMed2003

Insertion of the T3 DNA polymerase thioredoxin binding domain enhances the processivity and fidelity of Taq DNA polymerase.

Insertion of the T3 DNA polymerase thioredoxin binding domain (TBD) into the distantly related thermostable Taq DNA polymerase at an analogous position in the thumb domain, converts the Taq DNA polymerase from a low processive to a highly processive enzyme. Processivity is dependent on the presence of thioredoxin. The enhancement in processivity is 20-50-fold when compared with the wild-type Taq DNA polymerase or to the recombinant polymerase in the absence of thioredoxin. The recombinant Taq DNA pol/TBD is thermostable, PCR competent and able to copy repetitive deoxynucleotide sequences six to seven times more faithfully than Taq DNA polymerase and makes 2-3-fold fewer AT-->GC transition mutations.

Amino Acid Sequence↗
PubMed2003

Epithelial Na, K-ATPase expression is down-regulated in canine prostate cancer; a possible consequence of metabolic transformation in the process of prostate malignancy.

BACKGROUND: An important physiological function of the normal prostate gland is the synthesis and secretion of a citrate rich prostatic fluid. In prostate cancer, citrate production levels are reduced as a result of altered cellular metabolism and bioenergetics. Na, K-ATPase is essential for citrate production since the inward Na+ gradients it generates are utilized for the Na+ dependent uptake of aspartate, a major substrate for citrate synthesis. The objective of this study was to compare the expression of previously identified Na, K-ATPase isoforms in normal canine prostate, benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma (PCa) using immunohistochemistry in order to determine whether reduced citrate levels in PCa are also accompanied by changes in Na, K-ATPase expression. RESULTS: Expression of Na, K-ATPase alpha1 and beta1 isoforms was observed in the lateral and basolateral plasma membrane domains of prostatic epithelial cells in normal and BPH prostates. Canine kidney was used as positive control for expression of Na, K-ATPase alpha1 and gamma isoforms. The alpha1 isoform was detected in abundance in prostatic epithelial cells but there was no evidence of alpha2, alpha3 or gamma subunit expression. In advanced PCa, Na, K-ATPase alpha1 isoform expression was significantly lower compared to normal and BPH glands. The abundant basolateral immunostaining observed in normal and BPH tissue was significantly attenuated in PCa. CONCLUSION: The loss of epithelial structure and function and the transformation of normal epithelial cells to malignant cells in the canine prostate have important implications for cellular metabolism and are accompanied by a down regulation of Na, K-ATPase.

Journal Article↗
PubMed2003

Chondrosarcoma of bone complicating Ollier's disease: report of a favourable response to radiotherapy.

Because chondrosarcoma of bone is traditionally thought to be a radioresistant malignancy, it is usually managed surgically. We report a case of multifocal chondrosarcoma arising in Ollier's disease for which the patient declined surgery. He was given a course of radical radiotherapy that resulted in symptom palliation and a radiologically confirmed response before he died of disseminated disease. In patients with inoperable chondrosarcoma, radiotherapy can provide palliative benefit.

Bone Neoplasms↗
PubMed2003

Optimizing the search algorithm for protein engineering by directed evolution.

An in silico protein model based on the Kauffman NK-landscape, where N is the number of variable positions in a protein and K is the degree of coupling between variable positions, was used to compare alternative search strategies for directed evolution. A simple genetic algorithm (GA) was used to model the performance of a standard DNA shuffling protocol. The search effectiveness of the GA was compared to that of a statistical approach called the protein sequence activity relationship (ProSAR) algorithm, which consists of two steps: model building and library design. A number of parameters were investigated and found to be important for the comparison, including the value of K, the screening size, the system noise and the number of replicates. The statistical model was found to accurately predict the measured activities for small values of the coupling between amino acids, K <or= 1. The ProSAR strategy was found to perform well for small to moderate values of coupling, 0 <or= K <or= 3, and was found to be robust to noise. Some implications for protein engineering are discussed.

Algorithms↗
PubMed2003

Anesthesia for corrective spinal surgery in a patient with Leigh's disease.

UNLABELLED: We report a case of anesthesia for posterior spinal fusion in a woman with Leigh's disease. This is a syndrome with a heterogeneous phenotype including ocular signs, motor signs, and respiratory disorder. It is associated with defects in the enzymes of the mitochondrial respiratory chain and central neural degeneration. Anesthesia is associated with worsening of the respiratory symptoms. Our patient underwent major spinal surgery as a palliative procedure. Her postoperative course was complicated by acute lung injury and sepsis. She ultimately failed a prolonged respiratory wean. Serial magnetic resonance imaging revealed a rapidly progressive necrosis of her brain stem and cervical spinal cord consistent with activation of her underlying Leigh's disease. This is the first report of spinal surgery in this patient group. It is also the first radiological demonstration of Leigh's disease reactivation in the postoperative period. Anesthesia and surgery are hazardous in this patient population, and respiratory symptoms make this a high-risk group. Surgery should only be undertaken with caution and after frank consent. Early postoperative imaging is recommended if there are respiratory complications. No drug prophylaxis has been shown to alter disease activation. IMPLICATIONS: Patients suffering from Leigh's disease are at high risk of serious postoperative respiratory morbidity. We present a case that demonstrates delayed respiratory complications and link this postoperative adverse outcome to aggressive reactivation of the underlying neurodegenerative condition.

Adult↗