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Biomedical subjects

M Hare

Publications and source records attributed to M Hare.

11 recordsLinked to original sources

Learning and morphological change.

An account is offered to change over time in English verb morphology, based on a connectionist approach to how morphological knowledge is acquired and used. A technique is first described that was developed for modeling historical change in connectionist networks, and that technique is applied to model English verb inflection as it developed from the highly complex past tense system of Old English towards that of the modern language, with one predominant "regular" inflection and a small number of irregular forms. The model relies on the fact that certain input-output mappings are easier than others to learn in a connectionist network. Highly frequent patterns, or those that share phonological regularities with a number of others, are learned more quickly and with lower error than low-frequency, highly irregular patterns. A network is taught a data set representative of the verb classes of Old English, but learning is stopped before reaching asymptote, and the output of this network is used as the teacher of a new net. As a result, the errors in the first network were passed on to become part of the data set of the second. Those patterns that are hardest to learn led to the most errors, and over time are "regularized" to fit a more dominant pattern. The results of the networks simulations were highly consistent with the major historical developments. These results are predicted from well-understood aspects of network dynamics, which therefore provide a rationale for the shape of the attested changes.

Humans

Inhibition of human neutrophil elastase and cathepsin G by a biphenyl disulfonic acid copolymer.

The sulfated polymer MDL 101,028 was found to be a potent-inhibitor of both human neutrophil elastase (HNE) and human neutrophil cathepsin G (CatG). Cleavage of synthetic substrate by HNE was inhibited by MDL 101,028 with an IC50 of 40 nM, while CatG was inhibited with an IC50 of 80 nM. Degradation of a macromolecular connective tissue substrate (cartilage proteoglycan) by HNE or CatG was inhibited by MDL 101,028 with an IC50 of approximately 10 microM. MDL 101,028 at concentrations of 4, 10 and 25 microM inhibited degradation of cartilage proteoglycan by human neutrophil lysate or stimulated human neutrophils by 54%, 70% and 79%, and 31%, 47% and 73%, respectively. Acute pulmonary injury resulting from the intratracheal (i.t.) instillation of HNE in rats was inhibited by 48%, 90% and 90% at concentrations of MDL 101,028 of 1.1 mg/kg, 2.8 mg/kg and 11 mg/kg. The duration of action of the compound after i.t. instillation was between 2 and 4 h. These results suggest that sulfated polymers such as MDL 101,146 may be useful as inhibitors of HNE-mediated lung injury.

Amino Acid Sequence

Cartilage degradation by cocultures of transformed macrophage and fibroblast cell lines. A model of metalloproteinase-mediated connective tissue degradation.

A number of human and mouse macrophage and fibroblast cell lines were examined for their ability to degrade cartilage proteoglycan in an attempt to establish a cell culture model of cartilage degradation. The mouse transformed macrophage cell line J774A.1 alone or in combination with the mouse transformed fibroblast cell line 10ME HD A.5R.1 were the only cell lines capable of extensively degradating cartilage proteoglycan. Incubation of the macrophage cell line J774A.1 on heat-killed cartilage disks resulted in the release of 36% +/- 8 (mean +/- SEM, n = 5) of the radiolabeled cartilage proteoglycan. The fibroblast cell line 10ME HD A.5R.1 alone did not degrade cartilage. However, cocultures of J774A.1 macrophages and 10ME HD A.5R.1 fibroblasts incubated on cartilage discs resulted in the release of 69% +/- 6 (mean +/- SEM, n = 5) of radiolabeled proteoglycan. There was little degradation of cartilage by macrophage/fibroblast cocultures during the first 3 days of culture. Cartilage degradation increased with each subsequent day in culture from 7% +/- 2 on day 4 to 68% +/- 3 (n = 3) by day 7. Supernatants from the macrophage/fibroblast cocultures were incubated with cartilage discs in the presence of general class-specific proteinase inhibitors. The metalloproteinase inhibitors 1,10 phenanthroline, EDTA, and recombinant tissue inhibitor of metalloproteinase were the only inhibitors that significantly blocked cartilage degradation by coculture supernatant. The cartilage degrading metalloproteinase in the macrophage/fibroblast coculture supernatant eluted as a broad peak on Sephacryl S-200HR with an estimated molecular mass between 22 and 55 kDa. These studies suggest that the macrophage/fibroblast coculture model of cartilage degradation may be a useful experimental system for the study of metalloproteinase-mediated connective tissue degradation.

Animals

Clinical check list for diagnosis of dementia.

A clinical check list for testing speech and parietal function as well as memory was used on 200 people admitted to a psychogeriatric assessment unit and repeated four to six weeks later, to see whether those with true dementias could be identified. The finding of errors in all three areas, particularly at the second test, accurately predicted cases with a poor outcome at six months follow-up. Amnesia alone was an unreliable indicator of dementia.

Aged