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Biomedical subjects

D M Taylor

Publications and source records attributed to D M Taylor.

At least 109 records · Page 6Linked to original sources

Mapping of six dominant cataract genes in the mouse.

The mapping of six mouse autosomal dominant cataract mutations that were induced by mutagenic treatment with radiation or ethylnitrosourea is described. Three, with differing phenotypes, mapped on Chromosome 1 between the loci of fuzzy (fz) and leaden (ln) and close to the locus of the gamma-crystallin gene cluster. One of these, Cat-2t, had previously been shown to be a member of a group of five allelic mutants. In addition, the previously known mutant eye lens obsolescence, Elo, maps to the same point. There are thus now eight mutants that map to this point and that may involve mutations in one of the gamma-crystallin genes. In addition, one of these mutants may be a homologue of Coppock cataract in man, which also maps close to the gamma-crystallin locus. Of the three remaining mutants, one, with the suggested symbol Cat-5, mapped to the proximal region of Chromosome 10, 23.4 +/- 4.0 cM from downless (dl), a region with homology to human 6q. A second mutant, provisionally designated Opj, mapped on Chromosome 16, 8.2 +/- 3.9 cM from the marker mahoganoid (md). Thus, it possibly has a homologue on human 22q, a region in which one of the beta-crystallin loci is sited. A third mutant, provisionally designated Npp, mapped to Chromosome 5, 1.3 +/- 0.9 cM from the locus of W, and thus probably has a homologue on human Chromosome 4.

Animals↗

Decontamination studies with the agents of bovine spongiform encephalopathy and scrapie.

Macerates of bovine brain infected with bovine spongiform encephalopathy (BSE) agent, and rodent brain infected with the 263K or ME7 strains of scrapie agent, were subjected to porous-load autoclaving at temperatures between 134 and 138 degrees C for < or = 60 min. Bioassay in rodents showed that none of the regimens produced complete inactivation. Homogenates of BSE-infected bovine brain were exposed for < or = 120 min to solutions of sodium hypochlorite or sodium dichloroisocyanurate containing < or = 16,500 ppm available chlorine. There was no detectable survival of infectivity after the hypochlorite treatments but none of the dichloroisocyanurate solutions produced complete inactivation. Homogenates of BSE-infected bovine brain, and rodent brain infected with the 263K and ME7 strains of scrapie agent, were exposed for < or = 120 min to 1M or 2M sodium hydroxide but no procedure produced complete inactivation of all agents tested.

Animals↗

Energy intake, anthropometry and blood pressure of expeditioners in the Antarctic.

The energy intakes, anthropometry and blood pressure of 62 expeditioners at one Australian sub-Antarctic (Macquarie Island) and two Antarctic stations (Davis and Casey) were examined over a 12 month period. High mean energy intakes were found at all stations (approximately 16,000 kJ/subject/day). Mean subject body weight tended to rise during the winter months (midway during the study) and fall during the spring, although there were no significant changes (p < 0.05) seen at any of the stations over the year. Subjects were generally leaner at the end of 12 months as evidenced by significant falls (p < 0.01) in mean sum of skinfold thickness at two stations over the year. At all stations, blood pressure trended downwards during the year, with significant rises (p < 0.01) seen at one station during the spring. Two 12-week dietary intervention periods were introduced during the year at one of the Antarctic stations to investigate the effects of low-cholesterol (< 300 mg/day), low-fat (< 30% of energy) and high-fibre (> 30 g/day) diets. The average energy intake/day during these two periods (14,973 kJ and 14,515 kJ) was slightly less than during the baseline diet (average of 16,228 kJ). This was reflected in the anthropometric measurements with the mean body weight, sum of skinfold thickness and waist/hip ratios trending down during the diet periods. The study confirms earlier reports of high mean energy intake in Antarctica and suggests that the techniques of measuring intake may have been more accurate than those used in large population studies where intake may have been under-estimated. The results indicate seasonal fluctuations in blood pressure and anthropometric parameters and demonstrate that these anthropometric parameters were affected by the balance of energy intake and activity.

Adult↗

Increased basal levels of free plasminogen activator activity found in human aqueous humor.

PURPOSE: To quantify the basal free t-PA activity in human aqueous humor. METHODS: Human aqueous humor obtained by simplified pipette paracentesis at cataract surgery was tested for free t-PA activity in a revised 15-hour amidolytic assay using a t-PA standard curve (n = 15). Total antigenic levels of PAI-1, the principal PA inhibitor, were determined using an ELISA kit. The available PAI-1 activity was tested indirectly using anti-human PAI-1 antibody blocking before t-PA activity assay (n = 11). Plasminogen activator type was determined by anti-human t-PA and urokinase (u-PA) antibody blocking before activity assay (n = 7). RESULTS: Free PA activity ranged widely (0.072 to 0.47 IU/ml; mean, 0.20 +/- 0.10 IU/ml) and was almost completed inactivated (> or = 89%) by antibody against human t-PA but not by the u-PA antibody. PAI-1 total antigen also ranged widely between (0.25 to 8.0 ng/ml; mean, 2.25 +/- 2.54 ng/ml). However, pretreatment of samples with PAI-1 antibody or by acidification (pH 3.2) to inactivate inhibitors did not increase t-PA activity levels. CONCLUSIONS: A basal-free t-PA activity, which is predominantly t-PA, is present in human aqueous humor at approximately 20 times higher levels than previously found with an earlier assay. This activity is estimated to represent roughly 10% of total released t-PA antigen. PAI-1 is present in aqueous humor at levels considerably lower than reported values for plasma in a predominantly PA-complexed or inactive form.

Aged↗

Tissue plasminogen activator activity in human aqueous humor.

PURPOSE: To determine the levels of free plasminogen activator activity in human aqueous humor and to identify the type of activity (i.e., tissue-type t-PA or urokinase-type u-PA) that is responsible. METHODS: Aqueous humor was obtained by a simplified pipette paracentesis before cataract surgery in 31 subjects, ages 57 to 93 years. Levels of plasminogen activator activity were determined using a modified 17-hour specific amidolytic assay. The type of plasminogen activator was investigated in selected samples based on its dependence on soluble fibrin, inhibition by amiloride, and specific antibody blocking. Activity-antigen ratios were compared in seven samples. RESULTS: Plasminogen activator (PA) activity was present in all samples tested. PA activity ranged widely between 0.54 and 26.7 mIU/ml, with a mean value of 10.8 +/- 8.1 mIU/ml. Soluble fibrin, a known stimulator of tissue-type plasminogen activator (t-PA), was required in the assay system. Its absence decreased the measured activity by more than 90%. Amiloride, a known inhibitor of urokinase-type PA, had little or no effect in selected samples tested. The activity was blocked by anti-human t-PA antibodies but not by antibodies against human u-PA, further defining the type of PA responsible for the detected activity. t-PA antigen levels showed less variation among individuals than did activity levels. Antigen-activity ratios ranged between 89 and 552. CONCLUSION: Plasminogen activator activity is present in the human aqueous humor in measurable quantities. The type of PA activity present is almost exclusively t-PA. t-PA activity varies more widely than antigen, as is the case in plasma.

Aged↗

On the toxicity of low doses of tetrasodium-ethylenediamine-tetraacetate (Na-EDTA) in normal rat kidney (NRK) cells in culture.

The toxicity of tetrasodium-ethylenediaminetetraacetate (Na-EDTA) was investigated in normal rat kidney cells (NRK-52E, American Type Culture Collection) in culture. Cell death and reduced colony-forming ability were observed at Na-EDTA concentrations < 100 microM, that is at concentrations lower than that required to chelate all the Ca2+ in the growth medium. No toxicity was observed when cells were exposed to 100 microM Zn- or Fe-EDTA, but the same concentration of Cu-EDTA was as toxic as Na-EDTA. Continuous exposure of the cell cultures to 5 microM Na- or Zn-EDTA for up to 7 weeks yielded no indications of toxicity.

Animals↗

Inactivation of SE agents.

The transmissible agents of the spongiform encephalopathies are relatively resistant to inactivation, and accidental transmission has occurred in animals and man. Rigorous chemical or physical procedures are required to achieve decontamination, and their effectiveness can only be determined by bioassay in animals. The best-defined model is scrapie in mice or hamsters, and this has been used in many of the studies to establish practical inactivation procedures. Although a number of techniques had been considered to be effective, more recent observations suggest that some of these may not always be completely reliable. Research continues on scrapie inactivation, and work is in progress to extend this knowledge to the BSE agent.

Animals↗

Bovine spongiform encephalopathy and its association with the feeding of ruminant-derived protein.

The epidemic of bovine spongiform encephalopathy which is currently afflicting British cattle probably represents transmission of the sheep disease, scrapie, to bovines. Epidemiological evidence suggests that the source of the infection was dietary, and implicates commercial cattle rations containing meat and bone meal. Although this product is manufactured worldwide from waste animal tissues, only sporadic cases of the cattle disease have occurred outside Great Britain where a unique combination of factors is considered to be involved; this includes changes in manufacturing methods together with the greater use of ovine raw material, an increasing proportion of which was probably scrapie-infected. A number of legislative measures have been introduced which should lead to the eventual elimination of the disease and prevent the occurrence of analogous diseases in other species. Meanwhile, pilot-scale spiking studies are underway to determine the relative decontamination efficiencies of various procedures used throughout the EC to manufacture meat and bone meal; more rigorous methods which are not currently employed are also being assessed.

Animal Feed↗

A surface plasmon resonance immunosensor based on the streptavidin-biotin complex.

It is shown that a streptavidin monolayer immobilized onto an evaporated gold film with biotin forms the basis of a highly specific sensing element. As an example, we show that by immobilizing the biotinylated antibody sex hormone binding globulin (alpha-SHBG) to the bound streptavidin monolayer a specific sensor for the antigen SHBG is readily fabricated. The interaction between immobilized antibody and corresponding antigen is monitored by surface plasmon resonance spectroscopy and is shown to follow a classic Langmuir isotherm. Detection of SHBG at nanomolar concentrations is demonstrated.

Antigens↗

NSPEC: a chemical speciation program for personal computers.

The details of a computer program, NSPEC, which simulates chemical speciation in aqueous systems, are presented. NSPEC has been designed explicitly for the IBM PC family of computers and is a departure from normal speciation programs in that it is controlled through interaction with a series of menus. The program is more user-friendly than other comparable speciation programs, can write the results files in formats suitable for importing into other programs, and, in many instances gives results faster than speciation programs running on microcomputers.

Algorithms↗

Bovine spongiform encephalopathy (BSE): a stimulus to wider research.

The severity of the epidemic of bovine spongiform encephalopathy which is currently afflicting cattle in the British Isles has stimulated a considerable research effort, much of which is directed toward understanding the aetiology and pathogenesis of the bovine disease. However, a significant thrust has also been orchestrated to address more fundamental issues such as the nature of the uncharacterized causal agents of the wider range of unusual animal and human diseases which share similar characteristics. The background to some of these research programmes is discussed, together with current aims and progress.

Animals↗