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Biomedical subjects

D M Simmons

Publications and source records attributed to D M Simmons.

41 records · Page 3Linked to original sources

Cushing's syndrome due to ectopic production of corticotropin-releasing factor.

A patient with Cushing's syndrome is described who had a metastatic medullary carcinoma of the thyroid which contained corticotropin-releasing factor. ACTH was found by an immunohistochemical method in the patient's pituitary, but not in the thyroid tumor. This is the second report demonstrating corticotropin-releasing factor in tumor tissue in this syndrome. Wider use of immunohistological methods can help distinguish this variety from other tumors associated with the ectopic ACTH syndrome when bioassays are not available.

Adrenocorticotropic Hormone↗

Punch sampling technique for quantitative identification of tritiated D-amphetamine.

A punch sampling, tissue solubilization, and scintillation counting technique has been devised for the quantitative identification of tritiated d-amphetamine in monkey brain tissue. The method is superior to autoradiography in identifying this water soluble radiochemical, and is easier and more anatomically precise than radiochemical assay of brain homogenates. This rapid and simple technique allows one to survey the whole brain by sampling unit volumes of individual structures verified by light microscopy. The procedure consists of six steps which may be spaced as the laboratory schedule permits: obtaining tissue blocks, preparation for sectioning, punch sampling and sectioning, preparing samples for scintillation counting, histological verification of sample sites, and analysis of scintillation count data. The technique has been successfully used to demonstrate a gradient of radioactivity following experimental intraventricular injections of 3H amphetamine.

Animals↗

Novel developmental specificity in the nervous system of transgenic animals expressing growth hormone fusion genes.

The development of methods for introducing foreign genes into the germ line of mice provides an approach for studying mechanisms underlying inducible and developmental gene regulation. Transgenic animals expressing foreign genes have thus been used to test models of the role played by specific DNA sequences in determining cell-specific expression. Results from these experiments suggest that tissue-specific expression is the consequence of a cis-acting regulatory sequence. However, these results do not exclude the possibility that cell-specific expression of some genes might be 'coded' by combinations of regulatory elements. We have previously described the production of transgenic mice from eggs microinjected with metallothionein-I/growth hormone (MGH) fusion genes, and now demonstrate that the juxtaposition of sequences from two different genes can be deciphered by cells to generate novel tissue specificities. Although expression of the endogenous metallothionein and growth hormone genes has not been detected in neuronal cells, transgenic mice clearly express an MGH fusion gene in a restricted subset of neurones. These results suggest a model in which tissue-specific patterns of expression of certain genes are determined by combinations of cis-acting regulatory sequences.

Animals↗

Functional acetylcholine receptor in PC12 cells reacts with a monoclonal antibody to brain nicotinic receptors.

The use of a variety of probes for neuronal nicotinic acetylcholine receptors has indicated that there are sites on neurons that bind the acetylcholine receptor antagonist alpha-bungarotoxin, but do not regulate cation channels in response to the binding of acetylcholine. Sites with high binding affinity for nicotine and for alpha-bungarotoxin also show different distributions in brain. A monoclonal antibody (mAb35) raised against acetylcholine receptors from Electrophorus electric organ has been used to purify receptors from chick brain. These receptors do not bind alpha-bungarotoxin but have a high affinity for nicotine and antibodies raised against them block the function of acetylcholine receptors in ciliary ganglia. We have raised a monoclonal antibody (mAb270) against acetylcholine receptors from chicken brain (P.J.W., R. Liu, S. Shimasaki, F. Esch, B. Morley & J.M.L., manuscript in preparation), which has been used to purify a similar receptor from rat brain. Here we show that this antibody identifies a functional nicotinic acetylcholine receptor in rat-neuron-like PC12 cells which is probably not encoded by the cDNA clone (lambda PCA48) previously suggested as a candidate for the acetylcholine receptor gene. Additionally, we show that mAb270 binds to the same areas of rat brain as nicotine.

Adrenal Gland Neoplasms↗