Search PubMed⌕ Search

Biomedical subjects

R Cowan

Publications and source records attributed to R Cowan.

At least 55 records · Page 3Linked to original sources

Breakage of double-stranded DNA due to single-stranded nicking.

Enzymes such as pancreatic deoxyribonuclease (DNase I) nick the single strands of double-stranded DNA. Two nicks sufficiently close on opposite strands will lead to breakage of the DNA molecule. This paper gives a mathematical model for the breakage of circular, supercoiled DNA under the action of an enzyme which nicks at random sites (or at preferred sites, these being in abundance and randomly positioned around the circle). After the first nick the DNA loses its supercoiled structure; after many nicks it breaks to become topologically linear; further nicks lead to fragmentation of this linear form. Formulae are given for the proportions of DNA molecules in each of the four classes: supercoiled; nicked but still circular; linear; fragmented. Formulae are also presented for the case when there is, in addition to nicking, simultaneous action of an endonuclease which produces direct double-stranded breaks in the DNA. Finally, a general theory is given for the case where a third type of enzyme, topoisomerase I, is operative, with all three DNA modifications taking place simultaneously.

DNA Topoisomerases, Type I↗

Determination of proliferative parameters from growth curves.

Data on total cell numbers and proportions of non-proliferative cells during the development of a tissue can be obtained by experiment. This paper shows, via a simple mathematical model, that data collected over a period of time determine the time profile of two proliferative parameters. These are the rate per proliferative cell per day at which cells divide and the average number of proliferative daughters which result from the division of a proliferative cell. One dataset alone does not provide sufficient information to determine either time profile. The findings are applicable where there is no significant cell death during the growth period. The mathematical model is fitted to data from chick neural retina.

Animals↗

Cell population dynamics during the differentiative phase of tissue development.

The dynamics of a cell population whose numbers are growing exponentially have been described well by a mathematical model based on the theory of age-dependent branching processes. Such a model, however, does not cover the period following exponential growth when cell differentiation curtails population size. This paper offers an extension to the branching process model to remedy this deficiency. The extended model is ideal for describing embryonic growth; its use is illustrated with data from embryonic retina. The model offers a better computational framework for the interpretation of a variety of data (growth curves of cell numbers, DNA histograms, thymidine labelling indices, FLM curves, BUdR-labelled mitoses curves) because age-distributions can be calculated at any stage of development, not just during exponential growth. Proportions of cells in the various phases of the cell cycle can be computed as growth slows. Such calculations show the gradual transition from a population dominated by cells which are young with respect to cell cycle age to one dominated by those which are old, and the effects such biases have on the proportions of cells in each phase.

Age Factors↗

Apparent complete lower esophageal sphincter relaxation in achalasia.

Seven of 23 patients (30%) seen in 2 yr with clinical and radiologic manifestations of achalasia underwent esophageal manometry demonstrating aperistalsis but apparent complete lower esophageal sphincter (LES) relaxation. Detailed clinical and laboratory evaluation suggests these patients may represent an early stage of achalasia. Duration of dysphagia and weight loss were significantly less (p less than 0.05), whereas LES pressure was similar in the 7 patients compared with the 16 more traditional achalasia patients. Isotope retention during radionuclide esophageal solid-emptying studies showed intermediate delay in emptying between normal subjects and achalasia patients. The duration of LES relaxation in this group was significantly shorter (p less than 0.01) than in normal subjects. Although complete, sphincter relaxation in these patients is functionally inadequate and may be the result of this shortened duration. The small size of standard manometry catheters may also contribute to this confusing finding. Apparent complete LES relaxation may be seen during manometry in achalasia and should not exclude its diagnosis.

Adult↗

The bifurcating autoregression model in cell lineage studies.

A model for cell lineage data is presented and analysed. The model is an extension of the classical first-order autoregression, used in time-series studies, to bifurcating data trees of general size and shape. Maximum likelihood theory is developed and compared with an extensive simulation study. Some properties of moment estimators are also presented.

Analysis of Variance↗

Average, binge and maximum alcohol intake in healthy young men: discriminant function analysis.

Blood samples and data on alcohol consumption, diet, exercise, smoking and drug use were collected from 89 undergraduate men affiliated with Greek houses. This population has previously been identified as one that consumed large amounts of alcohol among university undergraduates. Energy and nutrient intake from foods, exercise and drug use (except caffeine) were not different between those reporting consuming more than or less than 1 oz of alcohol per day. Multiple discriminant analysis using a panel of 35 blood tests correctly classified all subjects according to their self-reported intake of more than or less than 2 oz of alcohol per day; 96% were classified correctly at a cut point of 1.5 oz per day. Correct classification was 96-99% using a measure of binge consumption (quantity-frequency of heavy drinking). When maximum number of drinks per occasion was used in the discriminant function, 90-92% were correctly placed. Discriminant analysis based on a panel of common blood tests appears to be a promising technique to identify young drinkers who consume high amounts of alcohol.

Adolescent↗

[Narcolepsy and sudden onset of REM periods after nocturnal awakenings].

The objective of this study was to evaluate polysomnographic data, and especially the sudden onset of REM periods that occur after spontaneous awakenings during the night as characteristics of narcolepsy. We evaluated 148 consecutive patients with excessive daytime somnolence, except for those with sleep apnea. After clinical evaluation, all-night polysomnographic recording and multiple sleep latency test, 55 were diagnosed as narcoleptics and 93 were grouped as non-narcoleptics. The mean age of narcoleptics was 42.9 +/- 14.4 years old and the non-narcoleptics were 40.3 +/- 13.5 years old. Polysomnographic variables were compared between both samples using unpaired t test. Non-significant differences were found for: sex; total time in bed; total sleep time; time in stages 3, 4 and REM; number of arousals (less than 30 sec); number of body movements; REM density. The following significant differences were found: number of sleep onset REM periods during the night was higher for narcoleptics (p less than 0.001); total sleep time was lower for narcoleptics (p = 0.02); sleep latency was shorter for narcoleptics (p less than 0.001); REM latency to stage 1 was shorter for narcoleptics (p less than 0.001); time in stage 1 was higher for narcoleptics (p less than 0.001); time in stage 2 was lower for narcoleptics (p less than 0.001); number of full awakenings (greater than 30 sec) was higher for narcoleptics (p less than 0.001); number of awakenings longer than 5 minutes was higher for narcoleptics (p = 0.002). In conclusion, there were marked differences in the sleep architecture between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Branching process results in terms of moments of the generation-time distribution.

A number of simple formulae concerning the growth rate, doubling time, and age distribution of cell populations are in common usage. Many of these are invalid unless the generation times have no variation, a situation which occurs rarely. The correct formulae, which are available from the theory of age-dependent branching processes, are often ignored in the biological literature, perhaps due to their complexity. In this paper the major formulae from the theory of age-dependent branching processes are reorganised in terms of the mean, coefficient of variation, and skewness of the generation times. This leads to a greater insight into the theory and some simple formulae which account for the variability.

Analysis of Variance↗

A growth curve of cell numbers in the neural retina of embryonic chicks.

The growth of cell numbers in a normal embryonic population of neural retinal cells is described. The numbers were estimated from a time shortly after the neural retina first becomes recognizable to a time when numbers of retinal cells have become steady. Cell numbers were estimated in preparations of an entire neural retina dispersed into a suspension of single nuclei which were then counted in a Coulter counter. The growth curve of the ln numbers of cells has three phases of growth: an exponential phase during which there is steady-state exponential growth, a differentiative phase during which cell proliferation ceases and an end phase when no further change in cell numbers can be detected. The variances of the ln numbers of cells were highest during the exponential phase. The variances decreased during the differentiative phase and were at their lowest during the end phase. For variances to decrease requires mechanisms which control the final numbers of cells in the neural retina very precisely. The implications of mechanisms which operate by controlling cell lineages are explored.

Age Factors↗

The prognostic value of ambulatory blood pressures.

We reviewed the course of 1,076 patients with essential hypertension whose condition had been initially evaluated with both ambulatory BP (ABP) and office BP (OBP) measurements. During the period of follow-up (mean, five years), fatal cardiovascular events occurred in 75 patients, and nonfatal events occurred in 153. Each patient was classified according to the difference between the mean observed ABP at entry and that predicted from the mean OBP at entry by means of an equation for the linear regression of ABP on OBP. Life-table analyses demonstrated a significantly greater estimated cumulative ten-year incidence of both fatal and nonfatal events among patients with higher than predicted ABPs than among those with lower than predicted ABPs. Because OBPs were comparable in the two groups, we conclude that ABP was an important determinant of clinical outcome.

Adult↗

Clinical relevance of ambulatory blood pressure measurements.

The development of vascular complications in patients with hypertension is related to the level of blood pressure. A more representative measure of blood pressure is obtained by repeatedly measuring pressure after a period of rest or activity, and on several occasions. Really satisfactory values are, however, only obtained by multiple measurements throughout the day during a patient's normal activities. This is achieved with the Remler equipment (Model M-100-1 and M 2000). The working of the apparatus is described and its accuracy investigated. The findings of 675 untreated patients with essential hypertension are reviewed, and a few individual cases described which have been followed up to 10 years.

Adult↗