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Biomedical subjects

S Geddes

Publications and source records attributed to S Geddes.

10 recordsLinked to original sources

High microsatellite diversity and differential structuring among populations of the introduced common brushtail possum, Trichosurus vulpecula, in New Zealand.

An understanding of genetic variation and structure of pest populations has the potential to improve the efficiency of measures to control them. Genetic analysis was undertaken at five microsatellite loci in four native Australian and 14 introduced New Zealand populations of the common brushtail possum Trichosurus vulpecula in order to document these parameters. Genetic variation in New Zealand populations, and phylogenetic relationships among Australian and New Zealand populations, were largely predicted by the recorded introduction history. Populations on the two main islands of New Zealand had only slightly lower genetic diversity than did Australian populations, except that allelic richness on the South Is. was significantly lower. Diversity was higher in North Is. than in South Is. populations (although not significantly so) and mainland New Zealand populations as a group were significantly more diverse than offshore islands that represented secondary population size bottlenecks. In phylogenetic analyses South Is. and offshore island populations grouped with Tasmania, while North Is. populations grouped either with mainland Australia or were intermediate between the two Australian sources. This scheme was supported by admixture coefficients showing that North and South Is./offshore island populations were largely mainland Australian and Tasmanian in origin, respectively. Population structure differed markedly between the North and South Islands: populations were typically more genetically differentiated on the former than the latter, which also showed significant isolation-by-distance. Substantial linkage disequilibrium in most sampled New Zealand but no Australian population between microsatellite loci Tv16 and Tv27 suggests they may be physically linked.

Animals↗

Structure-function studies of an IGF-I analogue that can be chemically cleaved to a two-chain mini-IGF-I.

The structure and biological activities of two disulphide isomers of a C-region deletion mutant of insulin-like growth factor-I (IGF-I) which has an Asn--Gly link engineered at the junction of the A- and B-regions were studied before and after chemical cleavage. Circular dichroism (CD) spectra and binding affinity to IGF binding protein 3 (IGFBP3) indicated that the treatment with hydroxylamine did not disrupt the overall tertiary fold of the hormones. Cleavage restored some binding affinity for the IGF-I receptor in both isomers and weakly restored the ability to stimulate incorporation of tritiated thymidine into DNA in NIH 3T3 fibroblasts transfected with the human IGF-I receptor. Cleavage also restored metabolic capacity, as measured by the ability of the isomers to promote lipogenesis in isolated rat adipocytes through the insulin receptor. These results are consistent with the theory that binding of IGF-I to the IGF-I receptor requires a conformational change similar to that involved in insulin binding the insulin receptor. The weak affinity for the IGF-I receptor after cleavage is consistent with the belief that residues in the C-region interact with the IGF-I receptor. This structural difference between insulin and IGF-I gives each a higher binding affinity for its own receptor.

3T3 Cells↗

Lloyd-Davies position with Trendelenburg--a disaster waiting to happen?

PURPOSE: Lower limb compartment syndrome has been reported to occur after colorectal, urological, and gynecological procedures during which the patient's lower limbs are elevated for prolonged periods of time. METHOD: We investigated lower limb perfusion in a group of patients undergoing prolonged pelvic surgery both during and immediately after surgery, using intra-arterial blood pressure monitoring, laser doppler flowmetry, and pulse oximetry. RESULTS: Use of the modified lithotomy position was not associated with any demonstrable decrease in lower limb perfusion. The addition of 15 degrees head-down tilt, however, during pelvic dissection, led to an immediate and significant drop in lower limb perfusion (P < 0.05; Mann-Whitney U test). The subgroup of patients analyzed postoperatively showed a ten-fold increase (P < 0.01) in perfusion that was confined to the muscle compartment with no demonstrable increase in skin perfusion or intra-arterial pedal blood pressure. CONCLUSION: The use of the modified lithotomy position during pelvic surgery is not associated with lower limb ischemia. Addition of Trendelenburg position, however, causes profound ischemia of the lower limbs, and this is followed during the recovery period by hyperperfusion that is confined to the muscle compartments, which may put patients at risk of developing lower limb compartment syndrome.

Colectomy↗

Solution structure of a mini IGF-1.

Mini insulin-like growth factor 1, an inactive insulin-like growth factor 1 mutant lacking the C region, was studied by 2D NMR spectroscopy. Resonances were assigned for almost all protons of the 57 amino acid residues. The 3D structure of the protein was determined by distance geometry methods. Three helical segments; Ala 8-Cys 18, Gly 42-Phe 49, and Leu 54-Cys 61, were identified, corresponding to those present in wild-type insulin-like growth factor 1 and in single-chain insulin. Their relative orientation, however, was found to be changed. This change is connected with a displacement of the Phe 23-Tyr 24-Phe 25-Asn 26 beta-strand-like segment, i.e., of aromatic side chains known to be important for receptor binding. Thus, deletion of the C region of IGF-1 results in a substantial tertiary structural rearrangement that accounts for the loss of receptor affinity.

Amino Acid Sequence↗

Female twin with Hunter disease due to nonrandom inactivation of the X-chromosome: a consequence of twinning.

We report the occurrence of Hunter disease (mucopolysaccharidosis type II) in a karyotypically normal girl who was one of identical twins. Molecular studies showed nonrandom X-inactivation in both her fibroblasts and lymphocytes, while her normal twin showed equal usage of both X chromosomes. In view of previous reports of 7 pairs of identical female twins in which one had Duchenne muscular dystrophy, it seems that twinning may be strongly associated with nonrandom X-inactivation, and is not specific to the properties of the disease causing gene.

DNA Probes↗

An evaluation of herpes simplex virus antigenic markers in the study of established and developing cervical neoplasia.

Previous reports from our laboratory have shown that antiserum to "pure" AG-e, a type-common HSV antigen, specifically stains atypical cervical cells in indirect immunofluorescence. These observations have been confirmed and extended. Antisera were prepared against the two protein components of pure AG-e, designated ICP 12 (M. W. = 140,000) and ICP 14 (M. W. = 130,000), and were purified to radiochemical homogeneity by SDS-acrylamide gel electrophoresis. The antisera reacted as well as antiserum to pure AG-e in immunofluorescence with HSV-2-(G)-infected cells, and their reactivity was adsorbed with pelleted HSV-2 (G) virions. Unlike antiserum to pure AG-e, the antisera to ICP 12 and ICP 14 were nonreactive in immunodiffusion, and only antiserum to ICP 12 showed complement fixation with soluble viral antigenic mixtures. Antisera to pure AG-e, ICP 12 and ICP 14 specifically stained exfoliated cervical cells from patients with herpetic cervicitis and atypical cells from patients with atypia, carcinoma in situ (CIS) or invasive cancer. However, both the number of patients with a positive response and the number of staining atypical cells were greater with antiserum to pure AG-e than with antisera to ICP 12 or ICP 14, suggesting that AG-e is a superior marker. Cells staining with antiserum to pure AG-e, individually identified, were classified as atypia (mild to marked), CIS or cancer. The ability of the antiserum to pure AG-e to identify atypical cervical cells was compared to cytopathologic screening in a blind study of 26 patients. A good correlation (80% to 93.8%) was observed, indicating that pure AG-e is a sensitive and specific marker for the identification of atypical cells.

Antibody Specificity↗

Morphological identification of alpha-1-antitrypsin in pulmonary macrophages.

Pulmonary macrophages, as seen in the routine sputum samples obtained from smokers, reveal bipolar orangophilic spurs. By use of histochemical and immunofluorescence techniques, these spurs have been found to contain alpha-1-antitrypsin. Morphological localization of this substance within the pulmonary macrophages may be significant.

Histocytochemistry↗

Idiopathic pneumoperitoneum in a dog.

A 13-year-old, neutered male standard poodle with tachypnea and abdominal distension was diagnosed with pneumoperitoneum. Pneumoperitoneum can be due to a perforated gastrointestinal tract, penetrating abdominal wounds, gas-producing bacterial peritonitis, or it can be iatrogenically introduced during surgery. Idiopathic pneumoperitoneum is a condition diagnosed in humans after exclusion of perforated gastrointestinal tract and other known causes of free intra-abdominal gas. This report suggests that dogs may suffer from a similar syndrome.

Amputation, Surgical↗

Selectively withholding treatment from newborn babies.

Whether to withhold life-prolonging treatment from a severely handicapped newborn baby is a topical moral dilemma. Some recent prominent court cases in the UK highlight the ethical issues that have to be faced when considering such a decision.

Euthanasia, Passive↗