Biomedical subjects

L M McIntyre

Publications and source records attributed to L M McIntyre.

24 records · Page 2Linked to original sources

PubMed1998

Neuropathological and neuropsychological changes in "normal" aging: evidence for preclinical Alzheimer disease in cognitively normal individuals.

The presence of diffuse or primitive senile plaques in the neocortex of cognitively normal elderly at autopsy has been presumed to represent normal aging. Alternatively, these patients may have developed dementia and clinical Alzheimer disease (AD) if they had survived. In this setting, these patients could be subjects for cognitive or pharmacologic intervention to delay disease onset. We have thus followed a cohort of cognitively normal elderly subjects with a Clinical Dementia Rating (CDR) of 0 at autopsy. Thirty-one brains were examined at postmortem according to Consortium to Establish a Registry for Alzheimer Disease (CERAD) criteria and staged according to Braak. Ten patients were pathologically normal according to CERAD criteria (1a). Two of these patients were Braak Stage II. Seven very elderly subjects exhibited a few primitive neuritic plaques in the cortex and thus represented CERAD 1b. These individuals ranged in age from 85 to 105 years and were thus older than the CERAD la group that ranged in age from 72 to 93. Fourteen patients displayed Possible AD according to CERAD with ages ranging from 66 to 95. Three of these were Braak Stage I, 4 were Braak Stage II, and 7 were Braak Stage III. The Apolipoprotein E4 allele was over-represented in this possible AD group. Neuropsychological data were available on 12 individuals. In these 12 individuals, Possible AD at autopsy could be predicted by cognitive deficits in 1 or more areas including savings scores on memory testing and overall performance on some measures of frontal executive function.

Aged↗

PubMed1997

Hardy-Weinberg testing for continuous data.

Estimation of allelic and genotypic distributions for continuous data using kernel density estimation is discussed and illustrated for some variable number of tandem repeat data. These kernel density estimates provide a useful representation of data when only some of the many variants at a locus are present in a sample. Two Hardy-Weinberg test procedures are introduced for continuous data: a continuous chi-square test with test statistic T(CCS) and a test based on Hellinger's distance with test statistic T(HD). Simulations are used to compare the powers of these tests to each other and to the powers of a test of intraclass correlation T(IC), as well as to the power of Fisher's exact test T(FET) applied to discretized data. Results indicate that the power of T(CCS) is better than that of T(HD), but neither is as powerful as T(FET). The intraclass correlation test does not perform as well as the other tests examined in this article.

Alleles↗

PubMed1990

13C and 31P NMR studies of the pentose phosphate pathway in human erythrocytes.

31P NMR was used to monitor the concentrations of some of the intermediates of the non-oxidative pentose phosphate pathway (PPP) during the dissimilation of inosine and phosphate in dilute haemolysates. The temperature dependence of the ketone/hydrate ratio in dihydroxyacetone phosphate and the relative proportions of the isomers of sedoheptulose 1,7-bisphosphate were measured. The 31P NMR time courses were compared with the simulations obtained with a computer model of the modified F-type PPP.

Aldose-Ketose Isomerases↗

PubMed1989

Comparison of computer simulations of the F-type and L-type non-oxidative hexose monophosphate shunts with 31P-NMR experimental data from human erythrocytes.

Mathematical modelling was used to predict the behaviour of the two most favoured schemes for the operation of the non-oxidative hexose monophosphate shunt (HMS), the F-type and the L-type pathways. The models simulate the time courses of sugar-phosphate concentrations when various substrates are metabolized via each pathway. A 31P-NMR technique, with which to observe time courses of concentrations of sugar phosphates in a human red cell lysate, was developed. The accuracy of each hypothesised scheme was then evaluated by comparing predicted with observed data. The results were more consistent with time courses of sugar-phosphate levels predicted by the F-type (classical) pathway than those predicted by the L-type model. However, the accumulation of sedoheptulose 1,7-bisphosphate when a haemolysate was incubated with ribose 5-phosphated showed that the F-type pathway is not a complete description of the system of reactions. Transaldolase was demonstrated to be essential for the normal metabolism of sugar phosphates by haemolysates. The effects of the heat-inactivation of transaldolase on the metabolism of sugar phosphates were accurately predicted by the F-type model. The relevance of attempting to describe the reaction of the non-oxidative HMS as a distinct 'pathway' or 'cycle' is discussed.

Computer Simulation↗

PubMedDate not supplied

The effect of orchiectomy on lung cancer survival.

Gender is an independent prognostic factor for survival from lung cancer with the relative risk of lung cancer death for men compared to women being 1.3. This observation remains unexplained but in vitro data suggests a stimulatory effect of androgens on lung cancer growth. We hypothesized that androgen deprivation improves survival in men with lung cancer compared to hormonally intact men with lung cancer. On the basis of age, race and region, we matched 44 men with lung cancer and bilateral orchiectomy with 88 men who had lung cancer and no history of orchiectomy and compared their survival. Since hazards were non-proportional we chose the generalized gamma model to describe the survival function. The survival was significantly different between the two groups (p = 0.0048) with the orchiectomy group having a better two year overall survival. This retrospective study suggests that androgen depletion may significantly improve the short term survival of men with lung cancer but further, prospective investigation is required for confirmation.

Aged↗

PubMedDate not supplied

Rater agreement and utility of the mutagen-induced chromosome damage assay.

Chromosomal damage in peripheral blood lymphocytes induced by short-term in vitro exposure to the cytotoxic antibiotic bleomycin was first described in 1983 and proposed as a phenotypic assay for chromosome instability. This assay was subsequently described as potentially useful in assessing an individual's risk to environmental carcinogens in 1989. Since 1995 numerous published studies have used this assay to assess risk for cancer in the aerodigestive tract, particularly lung cancer, in various ethnic populations. Odds ratios up to 8.5 have been reported for individuals deemed "mutagen sensitive" (defined as > or = 1 chromatid break per metaphase averaged in 50 metaphases analyzed). While this phenotypic assay is appealing for lung cancer risk assessment it has not been reproduced by other investigators. Because of our interest in lung cancer biology, epidemiology, and genetics, we sought to independently assess the rater agreement of this assay. We found that 1) the assay is laborious to conduct (8 hours of labor) and relatively expensive (> $100), yet reducing the number of metaphases from 50 to 20 produced a reliable, less expensive, and less laborious test; and 2) the rater agreement of individual metaphase readings is poor, but agreement for a summary measure is high.

Bleomycin↗