mtDNA mutation rates--no need to panic.
Explore the source record for details and available documents.
Archaeology↗
Biomedical subjects
E Watson
Publications and source records attributed to E Watson.
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Ultrasonography of the umbilical structures in clinically normal calves.
The umbilical stalk, vein, and arteries, urachal region, and urinary bladder of 9 healthy Holstein calves were scanned ultrasonographically at weekly intervals from 1 day to 3 weeks of age. Four additional calves of representative ages, 1 day, 1 week, 2 weeks, and 3 weeks were euthanatized after ultrasonographic evaluation of the umbilical structures. Umbilical structures from these 4 calves were dissected, photographed, and examined histologically to ensure normalcy. These gross specimens were correlated with the ultrasonographic images and compared with serial ultrasonograms of 9 calves. The ultrasonographic scanning technique and the appearance of normal umbilical stalk, arteries, and vein, and urachus in calves were different from those described for foals. The umbilical vein of calves was scanned from the umbilical stalk to the liver along the right abdominal wall. Two veins, which merged within the body wall, were identified within the stalk. Umbilical arteries were not found within the umbilical stalk; they ended abruptly near the apex of the urinary bladder. A urachal remnant was not identified in any of the calves. A range of normal values for measurement of the umbilical stalk, umbilical arteries, and umbilical vein at 3 sites was determined. The described ultrasonographic appearance and measurements of the normal Holstein calf umbilicus may be used as a reference for evaluation of calves with internal umbilical abnormalities.
Age Factors↗
Dosimetry of technetium-94m-teboroxime.
Explore the source record for details and available documents.
Adult↗
What is your diagnosis? Penetrating foreign body in a horse causing delayed wound healing and a chronic draining tract.
Explore the source record for details and available documents.
Animals↗
Interaction of the C-terminal region of p105 with the nuclear localisation signal of p50 is required for inhibition of NF-kappa B DNA binding activity.
DNA binding of the homodimeric p50 subunit of NF-kappa B was inhibited by a bacterially expressed protein containing the ankyrin repeats present in the C-terminus of the p105 precursor but not by the I kappa B protein MAD-3. However p50 was retained on protein affinity matrices containing either the C-terminal ankyrin repeats of p105 or MAD-3. To investigate the interaction between p50 and proteins containing ankyrin repeats we have used a number of approaches to probe the accessibility of the p50 nuclear localisation signal in the protein complex. A monoclonal antibody recognising a linear epitope either very close to, or including, the nuclear localisation signal of the p50 protein could immunoprecipitate p50 homodimers but was unable to precipitate the protein when it was bound to the C-terminal region of p105. A close association between the nuclear localisation signal of p50 and the C-terminal region of p105 was also suggested by protease accessibility experiments. While the nuclear localisation signal of free p50 is extremely susceptible to cleavage with trypsin the same site is masked in the presence of the C-terminal ankyrin repeats of p105 and, to a lesser extent MAD-3. Removal of the nuclear localisation signal by trypsin digestion generates a protein that is fully competent for DNA binding but is refractile to inhibition by the C-terminal ankyrin repeats of p105. Addition of DNA destabilises complexes between p50 and ankyrin repeat containing proteins, increasing the susceptibility of the nuclear localisation signal to trypsin cleavage. The data suggest that there is a rapid exchange of p50 between complexes containing DNA or I kappa B proteins via a metastable complex containing DNA, p50 and I kappa B.
Amino Acid Sequence↗
Capillary electrophoretic separation of human recombinant erythropoietin (r-HuEPO) glycoforms.
Free zone capillary electrophoresis was investigated for the separation of glycoforms in recombinant erythropoietin (r-HuEPO). Reduction of electroendoosmotic flow through the addition of 1,4-diaminobutane and in the presence of urea resulted in optimum separation of all of the major glycoforms. Incubation of r-HuEPO with neuraminidase caused the slowest migrating species to diminish first in response, indicating that these contained the highest numbers of sialic acids. Additional evidence was obtained from spiking r-HuEPO with individual glycoforms isolated by preparative isoelectric focusing. These results indicate that the separation occurs in a predictable manner in order of increasing number of sialic acids contained in the glycoforms. As a consequence, the electropherograms provide the same information as that obtained from conventional gel isoelectric focusing, although separating by a different mechanism.
Animals↗
Recent controversy in radiation dosimetry.
Explore the source record for details and available documents.
Humans↗
Prodromal contractions and contractility in the feline bladder.
In the cat there are at least two distinct contractile states of the bladder during urine storage, one when prodromal contractions are present and one when non-micturating contractions are present. It is proposed that prodromal contractions are myogenic. This proposition was examined by comparing prodromal contractions before and after hypogastric nerve section as well as comparing prodromal contractions with the contractions that remain after sectioning of the hypogastric nerves. Key contraction characteristics, such as amplitude, maximum gradient and the variance of the intercontraction interval were not significantly changed by hypogastric nerve section, providing volume effects were corrected for, which suggested that prodromal contractions have a myogenic origin.
Animals↗
High-performance anion-exchange chromatography of asparagine-linked oligosaccharides.
Oligosaccharides released enzymatically by N-glycanase from fetuin, alpha-acid glycoprotein, human chorionic gonadotropin, platelet-derived growth factor, and kallikrein were chromatographed on a polymeric pellicular anion-exchange column at pH values of 5 and 13. Separations occurred into groups of peaks containing the same number of sialic acids with an additional separation dependent upon the nature of the antennary structure present. High pH conditions were required for the optimum separation of fetuin oligosaccharides, while low pH conditions significantly improved resolution of oligosaccharides obtained from the other glycoproteins. The analytical separation of oligosaccharides under conditions of low pH has important implications in the development of chromatographic mapping and identification techniques for N-linked oligosaccharides present on recombinant proteins.
Animals↗