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Biomedical subjects

M D Lynch

Publications and source records attributed to M D Lynch.

9 recordsLinked to original sources
PubMed2004

Selective pressure for a decreased rate of asymmetrical divisions within stem cell niches may contribute to age-related alterations in stem cell function.

Most mammalian continuously renewing tissues are maintained by stem cells located within stem cell niches. Each niche contains a number of stem cells that replicate asymmetrically to give differentiated cells and also undergo periodic deletion and compensatory replacement by symmetrical "self-renewal" divisions of stem cells remaining within the niche. It has been recognized that there is selective pressure for an increased rate of self-renewal divisions and that the increasingly likely consequence is neoplasia. However, to date it has not been appreciated that there is also an independent selective pressure for a decreased rate of asymmetrical divisions. In this article, the origin of this second type of selective pressure is explained and its consequences explored through the use of computer modeling. It is shown that age-related changes in a range of mammalian stem cell compartments can be understood in the context of a decreased rate of asymmetrical stem cell divisions with an increased propensity for self-renewal divisions. It is proposed that a decreased rate of asymmetrical divisions impairs the ability of old stem cell compartments to respond effectively to stress.

Aging↗
PubMed2004

The role of cellular senescence may be to prevent proliferation of neighboring cells within stem cell niches.

It has long been suspected that cellular senescence is an anticancer mechanism; however, it has been difficult to understand the advantage for the organism of retaining mutant cells in a postmitotic state rather than simply deleting them by apoptosis. It is proposed that in certain circumstances apoptosis promotes neoplasia by causing cells adjacent to the deleted cell to divide and that the role of cellular senescence is to prevent this. This may be particularly important in mammalian stem cell niches. After loss of a stem cell from a niche, another stem cell within the same niche divides symmetrically to restore the original number. The most important human malignancies arise from tissues maintained by stem cells, and there is increasing evidence that stem cells are the targets for at least the initial genetic changes that occur during carcinogenesis. If a subset of stem cells within a niche arises containing an oncogenic mutation, then tumor suppressor mechanisms promote apoptosis of these cells, and the niche restores the original number of stem cells by replication of both normal and mutated stem cells. Thus, paradoxically apoptosis increases turnover of mutant cells with associated risk of further genetic changes. However, if in addition mutant cells can become senescent, then the niche is progressively filled by senescent cells until either the mutant cells are eliminated or the niche is completely occupied by postmitotic cells, thereby preventing further evolution of the neoplastic clone. The consequences of this hypothesis are explored by computer modeling.

Apoptosis↗
PubMed2004

Malignant eccrine poroma in breast cancer-related lymphoedema.

We describe the first case of malignant eccrine poroma arising in a lymphoedematous site. The patient had long-standing lymphoedema of the upper limb following breast cancer treatment. Lymphoedema is a recognised complication of breast cancer treatment and a risk factor for the subsequent development of malignancy. Possible mechanisms for this are discussed.

Aged↗
PubMed2001

Tutor and student perceptions of the tutor's role in problem-based learning.

The role of the tutor in problem-based learning (PBL) differs dramatically from the traditional teaching role with which dental students and faculty are familiar. In this investigation, the dimensionality and complexity of the tutor role were assessed by first- and second-year dental students and by the tutors themselves using a twenty-four-item Likert-type questionnaire that served as one component of a comprehensive web-based assessment tool, the PBL-Evaluator. Evaluations were completed after each PBL case over a period of one and a half years by one class of students and for half a year by a second class. Exploratory principal components analyses of the responses to the questionnaire revealed a more complex factor structure for tutors than for students. While a five-factor solution was required for the tutors, a simpler two-factor solution sufficed for both groups of first-year students, and a three-factor solution was necessary for the second-year students. Although tutors displayed a more nuanced perspective on their performance than did students, items related to tutor modeling of professional conduct within tutorials consistently emerged as important for both.

Attitude↗
PubMed1998

The expanded Trail Making Test: rationale, development, and psychometric properties.

Many procedures have been employed to determine the specific cognitive components necessary for successful Trail Making Test (TMT) performance. Yet, there is still considerable disagreement in the literature as to what these components might be. The present study explores an alternative methodology to address this problem. By systematically varying the stimuli within the TMT format, it may eventually be possible to isolate the cognitive demands of this test. As the first step toward this goal, two experimental forms of the TMT, forms X and Y, were developed and subjected to empirical validation. The results indicate that this Expanded Trail Making Test possesses adequate concurrent and criterion validity to support the proposed methodology. The results also suggest that the psychometric properties of the TMT format are robust to alterations in test stimuli. Secondary benefits of this methodology, in terms of explaining between-group variance and in terms of cross-cultural assessment, are discussed.

Journal Article↗