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Biomedical subjects

E Watson

Publications and source records attributed to E Watson.

At least 19 recordsLinked to original sources
PubMed1999

Removal of an ectopic left kidney through a ventral midline celiotomy in a calf.

A 4-month-old Holstein heifer was examined because of poor growth, weight loss, dysuria, hematuria, pyuria, and a palpable mass in the right caudal quadrant of the abdomen. Clinicopathologic abnormalities included hyperfibrinogenemia, hyperproteinemia, anemia, and leukocytosis, and were consistent with chronic inflammation. Results of ultrasonographic evaluation of the umbilical cord remnants were suggestive of urachal abscess formation. Transabdominal ultrasonography of the kidneys was attempted; the right kidney appeared normal, but the left kidney could not be imaged. The calf was anesthetized and a ventral midline celiotomy was performed. The left kidney was larger than normal, was multilobulated, and contained multiple abscess. It had also broken through the peritoneum and was located in the peritoneal cavity. Unilateral nephrectomy and resection of umbilical cord remnants were performed. The calf recovered without complications and was healthy 5 years later. In this calf, ventral midline celiotomy provided sufficient surgical exposure for removal of the ectopic left kidney and resection of umbilical cord remnants.

Animals↗
PubMed1999

A systematic review of the literature exploring the role of primary care in genetic services.

BACKGROUND: In response to growing demands on genetics departments and advances in genetic medicine, it has been proposed that primary care should provide a frontline service in clinical genetics. However, there are concerns that primary care may be unwilling or ill prepared to take on this new role. OBJECTIVES: This study aimed to review systematically the literature exploring the role of primary care in delivering genetic services, and define potential methods of supporting primary care in the provision of genetics services. METHODS: Seven electronic databases were searched. This was complemented by contacting experts in the field and handsearching reference lists. In total, 230 papers were identified, including traditional reviews, of which 96 were examined in detail. Fifty-one papers are included in this review. On account of the heterogeneity of papers identified, we conducted a qualitative synthesis of the results, focusing on five key questions. RESULTS: GPs accept that they have an increasing role to play in genetics, but lack confidence in their ability to do so because of limited knowledge of clinical genetics. Evidence from pilot studies of cystic fibrosis screening provides the strongest evidence for the feasibility of providing genetic services in primary care. CONCLUSIONS: Although genetic issues currently constitute a relatively small part of the overall workload in primary care, this will almost certainly change in the light of new genetic discoveries. Educational programmes and referral guidelines, computer decision support and genetic nurse specialist outreach clinics may provide useful methods of supporting GPs in the new field of primary care genetics.

Attitude of Health Personnel↗
PubMed1998

Liver lobe torsion and liver abscess in a dog.

A 4-year-old Rhodesian Ridgeback had acute onset of vomiting, lethargy, and discolored urine. Physical examination revealed lethargy, pyrexia, weak femoral pulses, cardiac arrhythmia, distended abdomen, and signs of pain on abdominal palpation. Abdominal radiography and ultrasonography revealed a gas-containing lesion in the cranial portion of the abdomen. Preoperative care included administration of fluids, antibiotics, and antiarrhythmic medication. Exploratory laparotomy revealed hemobilia and a 360 degrees clockwise torsion of the papillary process of the caudate lobe of the liver. Clinical signs resolved completely after liver lobectomy, and the dog was alive 2 years after surgery. Torsion of a liver lobe is rare in dogs. Necrosis of the involved liver lobe can result in acute weakness, shock, and death. Hemodynamic stabilization, antibiotic treatment, and surgical intervention have been successful in treating this condition. Liver lobe torsion should be considered on the differential diagnoses list of acute abdominal pain.

Animals↗
PubMed1998

Evolution of the cytochrome P450 superfamily: sequence alignments and pharmacogenetics.

The evolution of the cytochrome P450 (CYP) superfamily is described, with particular reference to major events in the development of biological forms during geological time. It is noted that the currently accepted timescale for the elaboration of the P450 phylogenetic tree exhibits close parallels with the evolution of terrestrial biota. Indeed, the present human P450 complement of xenobiotic-metabolizing enzymes may have originated from coevolutionary 'warfare' between plants and animals during the Devonian period about 400 million years ago. A number of key correspondences between the evolution of P450 system and the course of biological development over time, point to a mechanistic molecular biology of evolution which is consistent with a steady increase in atmospheric oxygenation beginning over 2000 million years ago, whereas dietary changes during more recent geological time may provide one possible explanation for certain species differences in metabolism. Alignment between P450 protein sequences within the same family or subfamily, together with across-family comparisons, aid the rationalization of drug metabolism specificities for different P450 isoforms, and can assist in an understanding of genetic polymorphisms in P450-mediated oxidations at the molecular level. Moreover, the variation in P450 regulatory mechanisms and inducibilities between different mammalian species are likely to have important implications for current procedures of chemical safety evaluation, which rely on pure genetic strains of laboratory bred rodents for the testing of compounds destined for human exposure.

Amino Acid Sequence↗
PubMed1998

Passive transfer of growth-inhibitory antibodies raised against yeast-expressed recombinant Plasmodium falciparum merozoite surface protein-1(19).

Purified rabbit immunoglobulin raised against yeast-expressed recombinant FVO or 3D7 Plasmodium falciparum merozoite surface protein-1 (MSP-1) 19k-D C terminal fragment (MSP-1(19)) was transfused into malaria-naive Aotus nancymai monkeys that were immediately challenged with FVO asexual stage malaria parasites. Control monkeys received rabbit immunoglobulin raised against the sexual stage antigen Pfs25 or Aotus hyperimmune serum obtained from monkeys immunized by P. falciparum infection and drug cure. Passive transfer of rabbit anti-MSP-1(19) failed to protect against homologous or heterologous challenge and, when compared with negative controls, there were no differences in prepatent periods or time to treatment. Interestingly, rabbit anti-MSP-1(19), but not anti-Pfs25, immunoglobulin, and immune monkey serum prevented the development of antibodies directed against MSP-1(19) fragment by infected monkeys, indicating that the antibodies were reactive with native MSP-1(19) antigen in vivo. The prepatent period and time to treatment was greatly delayed in the two monkeys that received Aotus immune serum, both of which developed a chronic intermittent low level infection. In vitro parasite growth inhibition assays (GIAs) confirmed the presence of inhibitory activity (40% maximum inhibition) in concentrated anti-MSP-1(19) immunoglobulin (4.8 mg/ml), but the peak concentrations we achieved in vivo (1 mg/ml) were not inhibitory in vitro. Subinhibitory levels of anti-MSP-1(19) antibodies achieved by passive transfer were not protective against P. falciparum challenge.

Animals↗
PubMed1998

Characterization and viral safety validation study of a pasteurized therapeutic concentrate of antithrombin III obtained through affinity chromatography.

BACKGROUND AND OBJECTIVE: Antithrombin III (ATIII) concentrates are employed as therapy for congenital or acquired deficiencies. These concentrates are obtained from Cohn's fraction IV1. To improve yields, purity and safety, our group developed a procedure to obtain a pasteurized ATIII concentrate from the supernatant of Cohn's fraction II + III including a highly efficient heparin affinity chromatography purification and pasteurization as a viral inactivation step. DESIGN AND METHODS: Three steps of the manufacturing procedure (Cohn's fraction II + III precipitation, affinity chromatography and pasteurization) were selected to examine their efficacy in inactivating and/or removing the selected viruses. RESULTS: The industrial batches show a purity higher than 99% with approximately 95% native heparin binding ATIII. Only albumin and IgG could be detected at trace levels (0.07% and 0.16% of the total protein present, respectively). The specific activity of the product was approximately 6.65 IU/mg protein. Five viruses were spiked into the manufacturing starting materials and samples were collected at various points to determine the infection level of virus. The study showed a reduction factor (log 10) > or = 11.7 for HIV-1; > or = 8.1 for bovine herpes virus (analyzed as a model for herpes and hepatitis B viruses); > or = 8.1 for bovine diarrhea virus (model for hepatitis C and G) and > or = 6.0 for encephalomyocarditis virus (model for hepatitis A and other non-enveloped viruses). INTERPRETATION AND CONCLUSIONS: No biochemical alterations of the ATIII were detected in the final product. A high viral elimination capacity of the production process was demonstrated. So far, more than 32 million units of ATIII have been transfused in the form of this therapeutic concentrate without any detected seroconversion.

Antithrombin III↗
PubMed1997

Mitochondrial footprints of human expansions in Africa.

mtDNA studies support an African origin for modern Eurasians, but expansion events within Africa have not previously been investigated. We have therefore analyzed 407 mtDNA control-region sequences from 13 African ethnic groups. A number of sequences (13%) were highly divergent and coalesced on the "mitochondrial Eve" in Africans. The remaining sequences also ultimately coalesced on this sequence but fell into four major clusters whose starlike phylogenies testify to demographic expansions. The oldest of these African expansions dates to approximately 60,000-80,000 years ago. Eurasian sequences are derived from essentially one sequence within this ancient cluster, even though a diverse mitochondrial pool was present in Africa at the time.

Africa South of the Sahara↗
PubMed1997

Radiation absorbed dose to the embryo/fetus from radiopharmaceuticals.

Radiation protection practice requires the knowledge of estimated absorbed radiation doses to aid in the understanding of the potential detriment of various exposures. In nuclear medicine, the radiation doses to the internal organs of the subject are commonly calculated using the MIRD methods and equations. The absorbed dose to the embryo or fetus has long been an area of concern. The recent release of the pregnant female phantom series, and its incorporation into the MIRDOSE 3 computer software, has made possible the estimation of absorbed doses from radionuclides in the body to the fetus in early pregnancy and at 3, 6, and 9 mo gestation. A survey of several major medical institutions was made to determine the radiopharmaceuticals which might be given, whether intentionally or not, to women of childbearing years. Biokinetic data for these radiopharmaceuticals were gathered from various documents and other resources, and the absorbed doses to the embryo and fetus at these different stages of gestation from radiations originating within the mother's organs were estimated. In addition, information about activity distributed within the placenta and fetus was included where quantitative data were available. These absorbed dose estimates can be used to evaluate the risk associated with the use of different radiopharmaceuticals so that a more informed evaluation of the risks and benefits of the different procedures may be made. Further research is needed into the mechanisms and quantitative aspects of the placental transfer of many radiopharmaceuticals.

Embryo, Mammalian↗
PubMed1996

Improvement of virus safety of a S/D-treated factor VIII concentrate by additional dry heat treatment at 100 degrees C.

In order to increase the virus safety of a solvent/detergent-treated Factor VIII concentrate in regard to non-lipid coated viruses and to respond to the continuous discussion about reports on hepatitis A transmission by Factor VIII preparations, we have investigated the effect of a terminal dry heat treatment (30 min 100 degrees C) on HAV and various other viruses. By this treatment Hepatitis A virus was inactivated below detectable level after a few minutes (> 5.3 log10). Other RNA viruses such as the Human Immunodeficiency Virus (> 6.6 log10), bovine viral diarrhoea virus (> 6.6 log10) and vesicular stomatitis virus (> 5.8 log10) were also inactivated below detectable level. Pseudo rabies virus and reovirus Type 3 are inactivated by 5.7 and > 6.0 log10, respectively. SV40 and bovine parvo virus showed significant resistance to dry heat treatment. We conclude that the involvement of two strong virus inactivation steps, acting by different mechanisms, improves the virus safety of Factor VIII concentrates without destroying the Factor VIII activity. Moreover, the terminal 100 degrees C heat treatment for 30 min represents an effective measure to inactivate non-lipid enveloped viruses, in particular hepatitis A, which is resistant to solvent/detergent treatment.

Animals↗
PubMed1996

mtDNA sequence diversity in Africa.

mtDNA sequences were determined from 241 individuals from nine ethnic groups in Africa. When they were compared with published data from other groups, it was found that the !Kung, Mbuti, and Biaka show on the order of 10 times more sequence differences between the three groups, as well as between those and the other groups (the Fulbe, Hausa, Tuareg, Songhai, Kanuri, Yoruba, Mandenka, Somali, Tukana, and Kikuyu), than these other groups do between one other. Furthermore, the pairwise sequence distributions, patterns of coalescence events, and numbers of variable positions relative to the mean sequence difference indicate that the former three groups have been of constant size over time, whereas the latter have expanded in size. We suggest that this reflects subsistence patterns in that the populations that have expanded in size are food producers whereas those that have not are hunters and gatherers.

Agriculture↗
PubMed1995

Bioactive synthetic peptide of NDF/heregulin.

A folded synthetic peptide analog of NDF (NDF5), which has the 52 amino acid EGF-like domain of NDF alpha 2, has been characterized. The folded peptide stimulates tyrosine phosphorylation of Her2, Her3 and Her4 in breast cancer cells and competes with low affinity with full-length NDF alpha 2 for binding to the cells, while the linear one does not. NDF5 also induces morphologic changes in breast cancer cells. After several days treatment with NDF5 or NDF alpha 2, Her2-transfected MCF7 cells (Her2/MCF7) became similar morphologically to non-transfected MCF7. The biological activity of NDF5 is between 1/10 and 1/100 that of NDF alpha 2. This suggests that other motifs, such as the Ig and spacer domains may be important elements in conferring full activity.

Amino Acid Sequence↗
PubMed1995

Re-engineering care delivery to improve the health outcome of asthmatics in Campbelltown, New South Wales.

The pilot study for this project was established in February 1993 under a Health Communications Network initiative to improve the treatment results for asthmatics in Campbelltown, New South Wales. A user specific, standardized information environment was implemented across the community and hospital sectors linking General Practitioners, Specialist Consultants, and hospital doctors and nurses. The pilot included 20 General Practitioners, four pediatricians and respiratory physicians, and the nurses and doctors of a district hospital. ¿A multi-disciplinary team implemented the pilot, consisting of men and women from Campbelltown Health Service, Ernst & Young Health Services Consulting, and a major systems vendor. The team used process modeling tools to document the required changes to the roles and responsibilities of the individual practitioners and the impact of these changes on the cost of providing services and patient flow. Significant cost savings were anticipated from moving care out of the hospital and into the community. In the re-engineered environment, the General Practitioner became the case manager, responsible for guiding and coordinating the management of the patient's asthma, in consultation with the appropriate specialist consultants. The hospital continued to provide acute/emergency care. The level of sophistication of the information systems solutions was determined by the level of technical awareness of the users. Fax based communications were chosen to support the flow of timely and relevant information between the practitioners. A VAX based system was used as a data repository for the information collected by hospital staff and General Practitioners. The data repository acted as a clinical record for asthmatics who participated in the pilot. The clinical history of an asthmatic could then be viewed when a patient sought treatment from Campbelltown's Emergency Department during periods when the General Practitioner was not available. If a patient did seek emergency treatment, a record of the patient's visit was faxed immediately to the General Practitioner upon discharge from the hospital. Specialist consultants are independent practitioners in Australia. They were provided with a custom built application for their own personal computers. A key feature of this application was the automatic generation of letters to the General Practitioner to assist them in the management of asthmatics. The Specialist Consultants also identified a sub-group of high risk patients for whom additional clinical information was stored in the data repository at Campbelltown Hospital. Analysis of the patient information formed a core component of the project. Clinical outcomes for individual patients were forwarded to the General Practitioners regularly to assist them in their case management duties. System implementation in this re-engineered environment yielded the following: Strategies for managing the responses of clinicians and patients to the use of technology and a standardized information sharing environment. A means of assessing the system's impact on both the clinician-patient relationship and the professionals' relationship with other clinicians; The evolution of clinical use of information regarding individual patient's health outcome for the management of asthma; The integration of the information systems with policy and planning cycles for the Area Health Service; and The establishment of effective links with vendors of health service applications.

Asthma↗
PubMed1994

Arthroscopic removal of a fragment from an intercondylar eminence fracture of the tibia in a two-year-old horse.

A 2-year-old Standardbred colt was admitted because of lameness of the left hind limb. Physical examination revealed marked effusion of the left femoropatellar and femorotibial joints and grade IV/V lameness of the left hind limb. Radiography of the left stifle revealed a complete fracture of the medial tubercle of the intercondylar eminence of the tibia. Arthroscopy was used to provide diagnostic, therapeutic, and prognostic information. A cranial approach to the medial compartment of the femorotibial joint was performed. Manipulation of the medial tubercle revealed it to be unstable, but a direct view of the fracture was obscured by the cranial cruciate ligament. The fracture fragment was removed, and visual inspection revealed approximately half of the cranial cruciate ligament at its insertion on the intercondylar eminence to be compromised. Fourteen months after surgery, the horse had trained and had raced without lameness. Accurate evaluation of the intra-articular soft-tissue structures of the stifle is important because ligamentous and/or meniscal injuries often are the limiting factors in determining the potential for a successful outcome and future athletic performance.

Animals↗
PubMed1994

Structure determination of the intact major sialylated oligosaccharide chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells.

Recombinant human erythropoietin (rHuEPO) is used abundantly in the clinic to stimulate red blood cell growth in anaemic patients. The efficacy of the drug depends strongly on the extent of sialylation of its carbohydrate moiety. Prompted by conflicting literature reports on the issue, we reinvestigated the structures of the intact sialylated carbohydrate chains of rHuEPO expressed in Chinese hamster ovary (CHO) cells. The asparagine-linked oligosaccharides were released from rHuEPO with N-glycanase and fractionated by anion-exchange chromatography. The O-linked oligosaccharides were released under alkaline borohydride conditions. The primary structures of the major sialylated N- and O-type oligosaccharides were identified by 500-MHz 1H-NMR spectroscopy, supported by data from composition analysis, methylation analysis, low- and high-pH anion-exchange chromatography, and fast atom bombardment-mass spectrometry. The most abundant N-linked oligosaccharides in CHO cell-derived rHuEPO were found to be di-antennary, 2,4-branched tri-antennary, 2,6-branched tri-antennary and tetra-antennary chains (in the ratio of 7:6:5:82), with the latter containing between zero and three repeating N-acetyllactosamine units, in well-defined branches. The major (> 95%) di-, tri- and tetra-antennary structures are fully sialylated, i.e. they have two, three and four sialic acid residues, respectively, linked exclusively alpha(2-->3) to galactose residues. The majority (> 95%) of N-linked structures contain alpha(1-->6)-linked fucose at the proximal GlcNAc residue. The O-type mono- and disialyl oligosaccharides were characterized as a linear tri- and a branched tetra-saccharide, respectively.

Amidohydrolases↗
PubMed1994

Matrix-assisted laser desorption mass spectrometric analysis of a pegylated recombinant protein.

Matrix-assisted laser desorption ionization mass spectrometry (MALDI) has been investigated as a technique for the characterization of recombinant stem cell factor that had been covalently modified with polyethylene glycol (PEG) chains. The attachment of PEG chains produces a heterogeneous mixture of protein species that differ by 6000 Da. These differences in molecular weight could be readily determined by MALDI. The potential of MALDI as a general strategy for characterizing PEG-modified proteins is discussed.

Biotechnology↗