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P J Fitzgerald

Publications and source records attributed to P J Fitzgerald.

At least 145 records · Page 8Linked to original sources

Pancreas acinar cell regeneration. IX. Effect of actinomycin D on microstructure.

The morphologic effects of actinomycin D (ACTD) on normal and regenerating rat pancreas at three dosage levels were studied. ACTD at 1.0 and 0.5 mug/g total body weight produced reversible nucleolar and cytoplasmic changes in the acinar cells of the normal rat pancreas. The nucleolar alteration, zonal segregation, preceded the appearance of cytoplasmic lesions, implying a precursor relationship of the former to the latter. ACTD-induced cytoplasmic lesions were similar to those produced by ethionine. Since ethionine failed to produce nucleolar changes, it is suggested that the primary mechanisms of action of these two compounds are different, although the cytoplasmic lesions may occur by a common metabolic route. Regeneration of exocrine pancreas after injection of ethionine was affected by ACTD to different degrees depending upon the time of ACTD administration. Regeneration was prevented when ACTD, 0.5 mug/g, was given at day 11, the first day after the ethionine regimen; it was markedly decreased when ACTD was given at day 12, but much less affected when ACTD was given at later days. The effects at days 11 and 12 may have been related to prevention of DNA transcription and the formation of mRNAs at these days. The 0.05 mug/g dosage of ACTD had much less effect on normal and regenerating acinar cells, causing reduced cytoplasmic basophilia, decreased ergastoplasm and fewer free ribosomes, which suggests impairment of rRNA synthesis.

Animals↗

Pancreas acinar cell regeneration. X. Effect of actinomycin D on enzymatic activities.

The effect of actinomycin D (ACTD) at three dosage levels on the enzymatic activities of the normal rat pancreas was studied. At the 1.0 and 0.5 mug/g total body weight dosages there were decreased levels of amylase, lipase and chymotrypsin 1 hour after injection, a return to control levels shortly thereafter and a second drop in enzymatic levels a day or two later. Since ACTD is known to affect transcription of DNA within hours of administration, the first decrease may have reflected the effect of ACTD on the synthesis of enzyme mRNA. The lowest dosage, 0.05 mug/g, said to affect the synthesis of rRNA only, gave decreased enzymatic activities from 1-3 days after injection, suggesting that rRNA synthesis was involved, primarily. There were variable effects of ACTD on the enzymatic levels of regenerating pancreas after ethionine. When given for a single day early in the regeneration period, the injection of the 0.5 mug/g dosage, believed to affect both mRNA and rRNA synthesis, decreased considerably the levels of enzymatic activity on the fifth day of regeneration. Injection on multiple day early in regeneration, however, gave a paradoxic effect-higher levels than control values. The lowest dosage, 0.05 mug/g, affecting primarily rRNA, caused, even with multiple doses, a considerable decrease of enzymatic values to well below control levels. The paradoxic effect of the higher concentration of ACTD when given on multiple days may have been related to a decreased synthesis of the repressor of the mRNA for the enzyme, thereby making more mRNA available for synthesis of the enzyme.

Amylases↗

Histone changes during degeneration and regeneration of the pancreas.

1. Changes in the microstructure of histones from the pancreas were followed in rats given ethionine while on a protein-free diet. The lysine-rich histone F1 and the other histones extracted subsequently with 250mm-hydrochloric acid were isolated. When the ethionine-treated rats returned to the stock diet, regeneration of the pancreas was accompanied by an immediate increase in phosphate content of the total histone extract from which histone F1 had been removed. After 3-4 days there was a further increase in the phosphate content of this extract, and also in that of histone F1. 2. Similar changes in the phosphate and thiol+disulphide content of pancreas histones other than F1 were produced by starvation and re-feeding.

Animals↗

Mechanisms and outcomes of angioplasty and atherectomy assessed by intravascular ultrasound imaging.

Catheter-based intravascular ultrasound is a relatively new imaging tool to examine endovascular structure. One major goal for the development of intravascular ultrasound imaging has been to help clarify the mechanism of interventional therapies such as balloon angioplasty and directional atherectomy. Pathologic studies have suggested that plaque distribution and composition are key features that relate to initial and long-term success of coronary interventions. However, relatively little is known by angiography about the nature of plaque in the clinical setting. Intravascular ultrasound imaging provides a high resolution, "on-line" method of tracking the effects of catheter interventions such as balloon angioplasty and atherectomy. Because of its ability to visualize tissue beneath the luminal surface, ultrasound is generating new insights into the effect of plaque composition and distribution on the response to catheter therapies. With pre-procedure ultrasound imaging, it is increasingly possible to predict the result of a particular intervention, offering the potential for developing strategies of lesion-targeted therapy based on certain plaque characteristics. This article presents the early results of the GUIDE trial as a "works in progress" view of the role of intravascular ultrasound in helping interventionalists to understand--and to optimize--angioplasty and atherectomy.

Angioplasty, Balloon, Coronary↗

Delayed radionecrosis of the larynx.

Radiation has been used to treat carcinoma of the larynx for more than 70 years. Radionecrosis is a well-known complication of this modality when treating head and neck neoplasms. It has been described in the temporal bone, midface, mandible, and larynx. Laryngeal radionecrosis is manifested clinically by dysphagia, odynophagia, respiratory obstruction, hoarseness, and recurrent aspiration. The vast majority of patients who develop laryngeal radionecrosis present with these symptoms within 1 year of treatment; however, delayed presentations have been reported up to 25 years after radiotherapy. We present, in a retrospective case analysis, an unusual case of laryngeal radionecrosis in a patient who presented more than 50 years after treatment with radiotherapy for carcinoma of the larynx. The cases of delayed laryngeal necrosis in the literature are presented. This represents the longest interval between treatment and presentation in the literature. The details of the presentation, clinical course, and diagnostic imaging are discussed. The pathogenesis, clinical features, and treatment options for this rare complication are reviewed. Early stage (Chandler I and II) laryngeal radionecrosis may be treated conservatively and often observed. Late stage (Chandler III and IV) cases are medical emergencies, occasionally resulting in significant morbidity or mortality. Aggressive diagnostic and treatment measures must be implemented in these cases to improve outcome. This case represents the longest interval between initial treatment and presentation of osteoradionecrosis in the literature. A structured diagnostic and therapeutic approach is essential in managing this difficult problem.

Adult↗