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Biomedical subjects

W H Marsh

Publications and source records attributed to W H Marsh.

At least 37 records · Page 2Linked to original sources
PubMed1980

An in vitro model of pancreas carcinoma: N-nitroso-bis(2-hydroxypropyl)amine effects.

The carcinogenic effects of BHP in organ-cultured embryonic rat pancreas was demonstrated by both the transplacental route followed by organ culture and by direct addition on BHP to the culture medium. Both methods appeared efficient for in vitro induction of adenocarcinoma. The incidence of carcinoma was 70% by direct addition and 55% through transplacental administration. No acinar cell carcinoma developed in vitro, but the incidence of islet adenoma (54%) and islet carcinoma (11%) were relatively high. Transplacentally, BHP failed to produce any pancreatic tumor in vivo.

Adenocarcinoma↗
PubMed1980

An in vitro model of pancreas carcinogenesis: two-stage MNU--TPA effect.

Organ-cultured embryonic rat pancreata were exposed to either single or multiple doses of methylnitrosourea (MNU), a single dose of MNU followed by 12-O-tetradecanoyl-phorbol-13-acetate (TPA), or TPA alone and cultured for up to 6 weeks. Both single and multiple doses of MNU caused similar alterations during the first 10 days; ie, for 4 days the explants grew and differentiated as untreated explants, forming acini and ductules; thereafter the presence of MNU induced ductular proliferation and hyperplasia. Explants exposed to a single dose of MNU failed to proliferate beyond the 10th day of culture, showed progressive cell necrosis, and became almost completely necrotic in 6 weeks. Cells prepared from these explants on Day 10 and injected subcutaneously into nude mice also failed to grow and degenerated after 2 weeks. Multiple doses of MNU in vitro, however, produced further proliferation with an atypical cribriform pattern by the 15th day. In the absence of MNU, treatment with TPA alone had no histologic effect; but TPA treatment after a single dose of MNU promoted abnormal growth similar to that produced by multiple doses of MNU. Cells prepared from 10-day explants treated with a single dose of MNU followed by TPA grew subcutaneously in nude mice and formed nodules of atypical growth within 2 weeks. This system constitutes a simple model of short-latency chemical carcinogenesis.

Animals↗
PubMed1976

Long-term organ culture of embryonic rat pancreas in a chemically defined medium.

Embryonic rat pancreas anlagen have been grown in a chemically defined medium, subdivided biweekly and recultured for a total time of 10 weeks. The total mass increment during this time was in excess of 1000-fold. Samples were removed for light and electron microscope examination and for periodic measurement of enzymatic activity. Morphogenesis and cytodifferentiation occurred, peripheral outgrowth of epithelial buds was followed by the formation of interconnecting tubular structures and, eventually, by the appearance of distinctive acinar cells with zymogen granules. Mitotic figures became conspicuous at the periphery of explants within a day after each subdivision resulting in the formation of new tubular structures and acini. In general, the central area of the explants presented more mature acini with zymogen granules than was manifested at the periphery. The enzymatic activities of amylase, lipase, and chymotrypsin developed maximally during the first week of culture, reached a plateau level by the second week, and remained at a relatively constant level throughout the 10-week culture period.

Amylases↗
PubMed1976

An in vitro model of pancreatic carcinoma. Morphology and in vivo growth.

Pancreas rudiments from 13-day rat embryos were cultured in the presence of dimethylnitrosamine (DMN) for up to 10 weeks. Pancreas morphogenesis and differentiation occurred during the first week of culture. Acinar cell degeneration and necrosis began on the fifth day of culture and resulted in almost complete loss of acinar cells, islet cells, and fibroblasts by the end of the third week. This was associated with proliferation of cells without zymogen granules (centroacinar, ductal, or undifferentiated?). Theses cells formed glandular structures which extended to the surface of the explant. By the end of the fourth week, explants resembled ductal hyperplasia with foci of carcinoma in situ. The distribution pattern of neoplasia in 343 explants examined after 10 weeks of DMN treatment was as follows: 79% resembled ductal cell carcinoma; 9%, ductal hyperplasia; and 3%, acinar cell carcinoma. Nude mice injected with cell suspensions prepared from 10-week-old culture developed subcutaneous nodules. These nodules resembled duct cell carcinoma with desmoplastic reaction.

Animals↗
PubMed1972

Pancreas acinar cell differentiation. VII. Autoradiographic demonstration of intracellular radioactivity with with S-adenosyl-L-(C 3 H 3 ) methionine.

After rat pancreas anlagen were grown in an organ culture medium for 9 days and further incubated for 15, 30 or 60 minutes in media to which C(3)H(3)-Sadenosyl-L-methionine (C(3)H(3)-SAM) was added, autoradiography demonstrated radioactivity in the nucleolus, nucleus and cytoplasm of the acinar cell. Under similar circumstances, except that the anlagen were grown in a methionine-deficient (CD-MD) medium prior to incubation with C(3)H(3)-SAM, much greater concentrations of radioactivity were present in the nucleolus, nucleus and cytoplasm of the acinar cell than in the respective compartments of anlagen grown in control medium. The nucleolus showed the highest concentration of radioactivity in anlagen grown in either control or methionine-deficient medium. The nucleolus of the acinar cell of anlagen grown in CD-MD medium appeared to be the most undermethylated cellular compartment and was larger than the nucleolus of the acinar cell grown in the control CD medium, so it is possible that a deficient methylation of ribosomal RNA precursors led to a piling up of RNA in the nucleolus and a decrease in the flow of ribosomal precursors to the cytoplasm. Other substance might have been undermethylated and thereby have inhibited differentiation.

Animals↗
PubMed1972

Assay of nanogram levels of triglyceride lipase with a radioactive substrate.

A simple, sensitive procedure for the determination of triglyceride lipase activity has been developed. Nanogram amounts of oleic acid hydrolyzed from commercially available [(14)C]triolein were readily determined by the counting of the radioactivity of substrate and product after their rapid chromatographic separation on copper hydroxide-impregnated ion-exchange paper. Comparison of the relative amounts of radioactivity of the separated substrate and product gave an estimate of the percentage of hydrolysis of substrate. Comparison of results with a standard of pure lipase enables one to express the amount of hydrolysis in terms of the standard lipase. The results show that measured activity is a linear function of time up to 1 hr of incubation and of amounts of enzyme up to 125 ng. Reproducibility of the test is good.

Carbon Isotopes↗
PubMed1971

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↗
PubMed1971

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↗
PubMed1970

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↗