Biomedical subjects
Publications and source records attributed to P S Puri.
Volumetric estimates of the total number of granule cells in rats 30, 120, 200, and 365 days old increase linearly by approximately 35 to 43 percent between 1 month and 1 year. Total volume of the granular layer also grows linearly during that time. These results demonstrate a numerical increase in a neuronal population during adulthood in the mammalian brain.
This paper is a sequel to an earlier one (Neyman & Puri 1976), which deals with a hypothetical structural stochastic model of radiation effects in living cells. This model incorporates two important details of the mechanism overlooked in its mathematical treatment by the previous workers. The first is that the passage of a single "primary' radiation particle generates a "cluster' of secondaries which can produce "hits' that damage the living cells. The second detail concerns the time scales of radiation damage and of the subsequent repair. The events of arrival of a primary particle, its generation of secondary particles and their causing "hits' on the sensitive targets within the cells, all occur for all practical purposes instantly. On the other hand the subsequent changes in the damaged cell, such as repair, appear to require measurable amounts of time. While the biological and physical justifications for some of the underlying assumptions of the model were discussed in the previous paper referred to above, the present paper is concerned mainly with the mathematical details and also with how the model attempts to explain some of the empirical findings available in the literature.
The chance mechanism of cell damage and of repair in the course of irradiation involves two details familiar to biologists that thus far seem to have been overlooked in mathematical treatment. One of these details is that, generally, the passage of a single "primary" radiation particle generates a "cluster" of secondaries which can produce "hits" that damage the living cell. With high linear energy transfer, each cluster contains very many secondary particles. With low linear energy transfer, the number of secondaries per cluster is generally small. The second overlooked detail of the chance mechanism is concerned with what may be called the time scales of radiation damage and of the subsequent repair. The generation of a cluster of secondary particles and the possible hits occur so rapidly that, for all practical purposes, they may be considered as occurring instantly. On the other hand, the subsequent changes in the damaged cells appear to require measurable amounts of time. The constructed stochastic model embodies these details, the clustering of secondary particles and the time scale difference. The results explain certain details of observed phenomena.
The effects of coronary reperfusion on recovery of regional myocardial contractility and high energy pegmental changes in myocardial contractility were measured by means of a strain gauge-tipped, two-pronged catheter probe that measures myocardial fiber shortening. The curves of contraction are sensitive to the effects of ischemia. Coronary occlusion resulted in a rapid replacement of fiber shortening by passive fiber lengthening. If coronary occlusion was released and blood flow restored within 45 minutes, myocardial contractility returned promptly; adenosine triphosphate and creatine phosphate values were restored to normal. With coronary occlusion of 1 hour or longer, contractility failed to return in the immediate postperfusion period, but delayed return was recorded after 2 weeks of reperfusion. The extent of such recovery varied with the duration of preceding occlusion. Thus, reperfusion after 1 hour of occlusion was followed by return of fiber shortening over the entire reperfused region. With 2 hours of occlusion, recovery occurred over 75 percent of the reperfused myocardium. With 3 hours of occlusion followed by reperfusion, recovery of contractility was only partial, comprising approximately 60 percent of the reperfused region. High energy phosphate content of the reperfused myocardium showed a similar pattern of recovery. With occlusion of longer duration, reperfusion failed to restore contractility to any significant extent. These findings indicate that reperfusion after coronary occlusion of 1 to 3 hours may restore contractility over a period of 2 weeks, but the extent of such recovery diminishes with the increase in the duration of occlusion.
The effects on myocardial function, metabolism and ultrastructure of 60 minutes of reperfusion, instituted after 30, 60 and 90 minutes of occlusion of the left anterior descending coronary artery, were studied in 48 dogs. Twelve sham-operated dogs served as controls. Coronary occlusion for 60 or 90 minutes caused significant depression in the first derivative of left ventricular pressure (dP/dt) (P less than 0.05) that could not be reversed by reperfusion. Upon reperfusion, creatine phosphate stores in myocardium made ischemic for 30 and 60 minutes, but not for 90 minutes, returned toward control levels, but stores of adenosine triphosphate (ATP) and total nucleotides and the ATP/adenosine diphosphate ratio of myocardium subjected to 60 and 90 minutes of ischemia were further decreased. After 60 and 90 minutes of ischemia, swelling of the sarcoplasmic reticulum and mitochondrial damage (swelling, decreased matrix density and partial loss of cristae) were seen. Myofibrils were relaxed in all these groups. Reperfusion produced gross contraction of myofibrils and aggravated these changes in mitochondria and sarcoplasmic reticulum. In the hearts subjected to 90 minutes of ischemia these changes were gross. The levels of creatine phosphokinase, glutamic oxaloacetic transaminase and lactic dehydrogenase in the coronary sinus blood increased dramatically (P less than 0.05) upon reperfusion after 60 or 90 minutes of occlusion, indicating severe impairment of cell membranes. This secondary rise in serum enzyme activity during reperfusion should be taken into consideration when estimating the size of a myocardial infarct from enzyme changes alone. It appears that 60 and 90 minutes of ischemia cause severe myocardial damage that is not reversed by reperfusion maintained for 1 hour although longer periods of reperfusion may be beneficial.
Regional contractility measured as myocardial fiber shortening ceased 15-30 sec after coronary occlusion; myocardial ATP content was unaltered at this time. Contractility returned promptly if occlusion was released within 45 min. With occlusion of 1-3 hr, delayed recovery of contractility was observed 2 weeks after reperfusion; the extent of recovery diminshed with increasing period of occlusion. Concomitantly, there was parallel recovery of synthesis of ATP and creatine phosphate (CP) in reperfused myocardium.
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With reference to observations of supernovae in galaxies, a locally optimal test for the hypothesis of homogeneity of the observational units with respect to occurrence of supernovae (treated as a very rare event) is obtained for the case where the data are available only for those galaxies where at least one supernova is observed. It is shown that the loss in the asymptotic efficiency of the test due to lack of reporting of galaxies with no supernovae is very heavy and in fact is infinite for the case of very rare events.
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