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Biomedical subjects

Matthew H Kaufman

Publications and source records attributed to Matthew H Kaufman.

11 recordsLinked to original sources

Classification of proliferative pulmonary lesions of the mouse: recommendations of the mouse models of human cancers consortium.

Rapid advances in generating new mouse genetic models for lung neoplasia provide a continuous challenge for pathologists and investigators. Frequently, phenotypes of new models either have no precedents or are arbitrarily attributed according to incongruent human and mouse classifications. Thus, comparative characterization and validation of novel models can be difficult. To address these issues, a series of discussions was initiated by a panel of human, veterinary, and experimental pathologists during the Mouse Models of Human Cancers Consortium (NIH/National Cancer Institute) workshop on mouse models of lung cancer held in Boston on June 20-22, 2001. The panel performed a comparative evaluation of 78 cases of mouse and human lung proliferative lesions, and recommended development of a new practical classification scheme that would (a) allow easier comparison between human and mouse lung neoplasms, (b) accommodate newly emerging mouse neoplasms, and (c) address the interpretation of benign and preinvasive lesions of the mouse lung. Subsequent discussions with additional experts in pulmonary pathology resulted in the current proposal of a new classification. It is anticipated that this classification, as well as the complementary digital atlas of virtual histological slides, will help investigators and pathologists in their characterization of new mouse models, as well as stimulate further research aimed at a better understanding of proliferative lesions of the lung.

Animals↗

Hip disarticulation--the evolution of a surgical technique.

Introduced in the 18th century, hip disarticulation was considered to be one of the most radical operations performed for trauma or disease of the lower limb. The high morbidity and mortality associated with it ensured that it was a rarely performed procedure. It is fortunate that it remains extremely uncommon to the present day. Since the first successful hip disarticulation was described, a number of important advances have occurred. General medical care has improved dramatically and the development of anaesthesia, analgesics, antibiotics and blood transfusions has resulted in greatly decreased morbidity associated with this dramatic operation. This review on the history of hip disarticulation outlines the surgical evolution of the operation, the indications for its use and the techniques used. It draws on the early experiences and preferred techniques of the surgeons of the 19th century, with some discussion on the methods employed to reduce intraoperative haemorrhage. Further development of techniques in the 20th century is also described together with discussion on the evolution of hindquarter amputation.

Disarticulation↗

Harry Goodsir and the last Franklin Expedition, of 1845.

Henry Duncan Spens ("Harry") Goodsir was one of the younger brothers of John Goodsir, Professor of Anatomy at the University of Edinburgh from 1846 to 1867. Harry Goodsir qualified with the LRCS Edinburgh diploma in 1840, and was an anatomist and naturalist of the highest promise. He was Conservator of the Museum of the Royal College of Surgeons of Edinburgh from 1843 until 1845, when he was appointed assistant surgeon and naturalist to the Franklin Expedition. This sailed to the Arctic seas under Sir John Franklin, to find the North-West Passage, but was lost. Its fate was never determined satisfactorily, although several subsequent expeditions attempted to do so.

Anatomy↗

Sir William Newbigging (1772-1852) and Patrick Newbigging (1813-1864)-father and son presidents of the Royal College of Surgeons of Edinburgh.

Sir William Newbigging was a surgeon to the Edinburgh Royal Infirmary from 1802. While a dextrous operator, he was regarded principally as an excellent general practitioner. He was President of the Royal College of Surgeons of Edinburgh 1814-16 and was knighted by Queen Victoria in 1838. He had five sons, four of whom followed him into the medical profession. Four of his sons died young-only Patrick outlived him. When Patrick returned from a Continental tour in 1842 he joined his father's general practice and when Sir William died in 1852 he took it over. From 1861 to 1863 he was also President of the Royal College of Surgeons of Edinburgh. His last few years were plagued by ill health and he died in 1864, shortly after his fiftieth birthday.

Faculty, Medical↗

Genetic influences on ovulation of primary oocytes in LT/Sv strain mice.

A high proportion of LT/Sv strain oocytes arrest in meiotic metaphase I (MI) and are ovulated as diploid primary oocytes rather than haploid secondary oocytes. (Mus musculus castaneus x LT/SvKau)F1 x LT/SvKau backcross females were analysed for the proportion of oocytes that arrested in MI and typed by PCR for a panel of microsatellite DNA sequences (simple sequence repeat polymorphisms) that differed between strain LT/SvKau and M. m. castaneus. This provided a whole genome scan of 86 genetic markers distributed over all 19 autosomes and the X chromosome, and revealed genetic linkage of the MI arrest phenotype to markers on chromosomes 1 and 9. Identification of these two chromosomal regions should facilitate the identification of genes involved in mammalian oocyte maturation and the control of meiosis.

Animals↗

An ontology of human developmental anatomy.

Human developmental anatomy has been organized as structured lists of the major constituent tissues present during each of Carnegie stages 1-20 (E1-E50, approximately 8500 anatomically defined tissue items). For each of these stages, the tissues have been organized as a hierarchy in which an individual tissue is catalogued as part of a larger tissue. Such a formal representation of knowledge is known as an ontology and this anatomical ontology can be used in databases to store, organize and search for data associated with the tissues present at each developmental stage. The anatomical data for compiling these hierarchies comes from the literature, from observations on embryos in the Patten Collection (Ann Arbor, MI, USA) and from comparisons with mouse tissues at similar stages of development. The ontology is available in three versions. The first gives hierarchies of the named tissues present at each Carnegie stage (http://www.ana.ed.ac.uk/anatomy/database/humat/) and is intended to help analyse both normal and abnormal human embryos; it carries hyperlinked notes on some ambiguities in the literature that have been clarified through analysing sectioned material. The second contains many additional subsidiary tissue domains and is intended for handling tissue-associated data (e.g. gene-expression) in a database. This version is available at the humat site and at http://genex.hgu.mrc.ac.uk/Resources/intro.html/), and has been designed to be interoperable with the ontology for mouse developmental anatomy, also available at the genex site. The third gives the second version in GO ontology syntax (with standard IDs for each tissue) and can be downloaded from both the genex and the Open Biological Ontology sites (http://obo.sourceforge.net/).

Databases, Factual↗

Fetal abnormalities produced after preimplantation exposure of mouse embryos to ammonium chloride.

BACKGROUND: The aims of this study were to determine whether preimplantation exposure of mouse embryos to ammonium resulted in abnormal fetal development and to evaluate similar risks to the outcome of human assisted conception. METHODS: Mouse embryos cultured from the 1-cell stage were exposed to 0.3 mmol/l ammonium chloride for 3 days. Embryos cultured from the 2-cell stage were exposed to 0.3 or 0.6 mmol/l ammonium for 2 days. After transfer to the uteri of pseudopregnant recipient females, post-implantation development was evaluated on embryonic day 15.5 (E15.5) or E18.5. RESULTS: There was no consistent effect of preimplantation exposure to ammonium chloride on fetal or placental weights. All 101 E18.5 fetuses were normal but 5/217 E15.5 fetuses were abnormal (three exencephalic and two polydactylous), which was significantly higher than the 0/363 for the pooled groups of E15.5 control fetuses (P = 0.007). The combined E15.5 and E18.5 frequency was also significantly higher than the controls (5/318 versus 0/433; P = 0.013). CONCLUSIONS: These results support the conclusion that abnormal preimplantation culture conditions can cause fetal abnormalities in mice, but the risks may be lower than previously suggested. Further work is needed to evaluate the risk more fully but this risk should be considered when designing new strategies for human assisted conception.

Abnormalities, Drug-Induced↗

Corneal abnormalities in Pax6+/- small eye mice mimic human aniridia-related keratopathy.

PURPOSE: To investigate corneal abnormalities in heterozygous Pax6(+/Sey-Neu) (Pax6(+/-), small eye) mice and compare them with aniridia-related keratopathy in PAX6(+/-) patients. METHODS: Fetal and postnatal corneal histopathology, adult corneal thickness, and the distribution of K12-immunostained cells were compared in wild-type and Pax6(+/-) mice. RESULTS: Prenatally, the corneal epithelium was thinner in Pax6(+/-) fetuses than wild-type littermates, but the stroma appeared irregular, hypercellular, and thickened. The anterior chamber angle was obliterated, and the iris was hypoplastic from early developmental stages. The adult Pax6(+/-) corneal epithelium was thinner, had fewer layers, and included goblet cells, indicating repopulation from conjunctival epithelium. The ocular surface was often roughened, with epithelial vacuolation and lens tissue within the stroma. The corneal stroma was thicker centrally, with an irregular lamellar alignment. Many adult Pax6(+/-) corneas were vascularized or contained cellular infiltrates, but some remained clear. Corneal degeneration was age-related: Older Pax6(+/-) mice had prominent subepithelial pannus and more goblet cells in the peripheral corneal epithelium. Cytokeratin 12 stained very weakly in the peripheral and superficial corneal epithelium in 12-month-old Pax6(+/-) mice. CONCLUSIONS: Corneal abnormalities in Pax6(+/-) mice are similar to those in aniridia-related keratopathy in PAX6(+/-) patients. This extends the relevance of this mouse model of human aniridia to include corneal abnormalities. Incursion of goblet cells suggests impaired function of Pax6(+/-) limbal stem cells, abnormal expression of cytokeratin 12 may result in greater epithelial fragility, and corneal opacities in older mice may reflect poor wound-healing responses to accumulated environmental insults.

Animals↗

Wax models.

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Europe↗

John Aitken (d. 1790)--grinder or scholar?

John Aitken attended the University of Edinburgh between 1763 and 1769 but did not graduate MD. He gained the membership (i.e. fellowship) of the Royal College of Surgeons of Edinburgh in 1770, and was for two sessions Senior President of the Royal Medical Society. Between 1771 and 1790 he published numerous books and pamphlets on surgery, medicine, midwifery, anatomy and physiology. As a surgeon at the Royal Infirmary, from 1779, he lectured on most subjects in the medical curriculum. John Struthers was particularly scathing of Aitken's scholarship, and this article attempts to restore Aitken's reputation as a scholar and probably one of the first of the extra-academical lecturers, who taught both anatomy and surgery in Edinburgh from 1779 until his death in 1790.

Education, Medical↗