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Biomedical subjects

P J FITZGERALD

Publications and source records attributed to P J FITZGERALD.

At least 19 recordsLinked to original sources

Autoradiographic labelling of pancreatic acinar cells with thymidine-H3 during degeneration and regeneration.

The uptake of thymidine-H(3) in the acinar nuclei of the rat pancreas was studied by autoradiography after segmental excision of the pancreas, ligation of a segmental pancreatic duct, or ligation of the artery to the splenic segment of the pancreas. No sustained increase of nuclear labelling occurred in the rest of the pancreas after resection of the splenic segment. Ligation of the artery to the splenic segment produced significant increase of labelling three to five days post-operatively. Ligation of the duct to the splenic segment caused a similar significant increased labelling in acinar cells which were degenerating. The cells and nuclei were smaller than normal and there was a decrease of basophilia. The increase was of the same degree seen after ethionine necrosis. Decrease of intranuclear DNA-controlling influences, such as a histone, or the increased availability of DNA precursors might be responsible for this phenomenon.

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The degenerative changes in pancreatic acinar cells caused by DL-ethionine.

Degeneration of pancreatic acinar cells in rats injected with ethionine was studied by electron microscopy. The most conspicuous morphologic lesions occurred in the ergastoplasm. There was a widening of the endoplasmic reticulum, a decrease in number of membrane-associated ribosomes, and a development of fine and coarse vacuoles containing agranular disoriented membranes. Cytoplasmic ribosomes unassociated with membranes were less numerous. Nuclear changes consisted of a coarsening and clumping of the nuclear chromatin, chromatin margination, and increased osmiophilia and vacuolation of the nucleolus. Eight to ten days after the beginning of ethionine injections, changes in zymogen granules, mitochondria, and the Golgi apparatus appeared, but only after extensive damage to the acinar cell. The effects were consistent with ethionine's known interference with protein metabolism but also suggest disturbance in ribonucleic acid metabolism. The ergastoplasmic changes after ethionine were similar in some respects to the early lesions produced in liver parenchymal cells by fasting, to the changes occurring in animals on protein-free diets, or to some of the liver changes produced by azo dye carcinogens. The ribosomal and ergastoplasmic changes represent early morphologic expressions of the biochemical effect of ethionine.

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Restitution of pancreatic acinar cells following ethionine.

The regeneration of the pancreatic acinar cell was studied at four time periods after ethionine had destroyed most of the acinar cells. Within 2 days of the last ethionine injection, small basophilic cells (pre-acinar cells) with whorls of ergastoplasm or nebenkern were present. These cells also contained a decreased amount of Golgi substance, small zymogen granules, and a fine granularity of the nuclear matrix. They showed persistence of the characteristic ergastoplasm lesion produced by ethionine. Eight days after the last ethionine injection, the nebenkern was replaced by approximately normal appearing ergastoplasm and the nucleoli and Golgi bodies were enlarged. Zymogen granules were less dense but more abundant. Mitochondria were considerably enlarged. Most cells showed no ethionine lesions or only small foci of damage. Eighteen days after the cessation of ethionine, a good approximation of the normal acinar cell was present. The whorls of ergastoplasm appeared at a time (day 12) when basophilia was pronounced. Other studies showed that nucleic acid and protein precursors began to show an increased concentration in acinar cells at this time. The appearance of nebenkern during a phase of cellular recovery and its absence during a phase of replication when mitotic indices were high suggest that its presence is more indicative of ergastoplasmic synthesis than of cell multiplication as such. Possibly the increased density of zymogen granules was a reflection of this increased protein synthesis. The increase in size of Golgi apparatus occurred prior to the replenishment of zymogen granules and thus satisfied a precursor relationship for a possible role in the formation of these secretory structures. Evidence suggests that some injured acinar cells recover from the ethionine and protein-free regimen and give rise to most of the new acinar cells formed. It is possible that, under the severe conditions which prevailed, the centroacinar ductule cells may also have given rise to some acinar cells.

Acinar Cells↗

Changes in pancreatic acinar cells during protein deprivation.

After 10 days of a protein-free diet the acinar cells of the rat pancreas showed a coarsening of nuclear matrix, depletion of zymogen granules, some loss of ribosomes, and a widening of the spaces between ergastoplasmic membranes. In addition, there could be found, but rarely, a lesion of the ergastoplasm consisting of vacuoles of agranular, disoriented membranes, which was similar to a lesion produced by ethionine. Thereafter, a return toward normal structure occurred which was characterized by beginning increase in the size of the Golgi apparatus at 12 days, appearance of zymogen granules at 18 days, and a relatively normal appearing but smaller cell at 28 days. After 10 to 12 days of protein deprivation a reversal of many of the morphologic effects of protein deprivation was accompanied by a return toward normal of some pancreatic enzyme activities. Possibly this spontaneous return toward normal levels represented a raiding of protein stores, or it may have been an adaptive phenomenon.

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The nature, significance, and evaluation of the Schwarzschild-Villiger (SV) effect in photometric procedures.

The Schwarzschild-Villiger effect has been experimentally demonstrated with the optical system used in this laboratory. Using a photographic mosaic specimen as a model, it has been shown that the conclusions of Naora are substantiated and that the SV effect, in large or small magnitude, is always present in optical systems. The theoretical transmission error arising from the presence of the SV effect has been derived for various optical conditions of measurement. The results have been experimentally confirmed. The SV contribution of the substage optics of microspectrophotometers has also been considered. A simple method of evaluating a flare function f(A) is advanced which provides a measure of the SV error present in a system. It is demonstrated that measurements of specimens of optical density less than unity can be made with less than 1 per cent error, when using illuminating beam diameter/specimen diameter ratios of unity and uncoated optical surfaces. For denser specimens it is shown that care must be taken to reduce the illuminating beam/specimen diameter ratio to a value dictated by the magnitude of a flare function f(A), evaluated for a particular optical system, in order to avoid excessive transmission error. It is emphasized that observed densities (transmissions) are not necessarily true densities (transmissions) because of the possibility of SV error. The ambiguity associated with an estimation of stray-light error by means of an opaque object has also been demonstrated. The errors illustrated are not necessarily restricted to microspectrophotometry but may possibly be found in such fields as spectral analysis, the interpretation of x-ray diffraction patterns, the determination of ionizing particle tracks and particle densities in photographic emulsions, and in many other types of photometric analysis.

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