Biomedical subjects
Publications and source records attributed to F Sutton.
A myriad of both primary and secondary hematologic and gastrointestinal system-related clinical problems may exist in the cancer patient. This review outlines a standard approach to the prompt diagnosis and therapeutic intervention for these clinical issues.
We have found that cholinergic neurons in spinal cord-dorsal root ganglion cultures derived from E12-E13 mouse embryos are sensitive, as measured by changes in choline acetyltransferase activity, to factors secreted by non-neuronal cells derived from the same tissue at an identical developmental stage. Conditioned medium was produced by incubating non-neuronal cultures for 4 days in defined medium. The cholinotrophic activity present in the conditioned medium had a molecular weight of greater than 50,000 as determined by ultrafiltration and bound wheat germ lectin and heparin sepharose. Total RNA isolated from the non-neuronal cells, used to produce the conditioned medium, was translated in frog oocytes. Conditioned medium from the injected oocytes was also found to contain cholinotrophic activity. In contrast, the conditioned medium from water-injected oocytes was inactive. The interaction between the cholinotrophic activity in conditioned medium from frog oocytes and known second messengers was also examined. Dibutyryl cyclic AMP produced a concentration-dependent increase in choline acetyltransferase activity. If a maximal effective dose of dibutyryl cyclic AMP was added in conjunction with a maximal effective dose of conditioned medium from oocytes injected with total RNA a nearly additive response was noted. In contrast, the phorbol ester, phorbol 12-myristate 13-acetate, produced a biphasic change in the level of choline acetyltransferase activity; with lower doses stimulating and higher doses inhibiting the enzyme activity. When conditioned medium from oocytes injected with non-neuronal cell RNA was added in conjunction with the phorbol ester a decrease in the physiological response was noted.
Voltage-sensitive sodium (Na) channel currents recorded from mammalian cardiac muscle are blocked by tetrodotoxin (TTX) with a Kd of 1-3 microM. We have observed a Kd for TTX of 4-10 nM for Na currents recorded from Xenopus oocytes injected with RNA extracted from rabbit cardiac muscle. This result suggests that the degree of TTX sensitivity of Na channels encoded by cardiac muscle mRNA is in part determined by post-translational modification(s) or of associations with accessory proteins in the membrane.
The structural gene encoding a mutant Escherichia coli phosphoenolpyruvate carboxylase deficient in regulation by fructose 1,6-bisphosphate (Fru-P2) was isolated from total E. coli PpcI genomic DNA. This mutant gene is located on a 4.4-kilobase SalI DNA fragment which, when ligated to SalI-digested pBR322, resulted in the generation of the plasmid pFS16. Detailed restriction mapping of the wild-type and mutant genes for phosphoenolpyruvate carboxylase revealed the presence of a ClaI restriction site at position 563 of the mutant gene only. This ClaI site is located on a 289 PvuII/DdeI fragment which codes for amino acid residues 174-270 of the phosphoenolpyruvate carboxylase enzyme. When this portion of the mutant gene is present in chimeras of the wild-type and mutant genes, the phosphoenolpyruvate carboxylase produced cannot be activated by Fru-P2. The mutation resulting in the generation of the ClaI site in the mutant gene has also resulted in an amino acid substitution at residue 188; threonine in the wild-type enzyme has been replaced by isoleucine in the mutant enzyme. Comparison of the nucleotide sequence of this 289-base pair PvuII/DdeI region of the mutant gene with its homologous region in the wild-type gene verified that this mutation, which resulted in the generation of the ClaI site, is the only change that has occurred on this 289-base pair fragment of the mutant gene, and thus the amino acid replacement of threonine by isoleucine is the only change that could be linked to the inability of the mutant enzyme to be activated by Fru-P2.
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The subject of left ventricular involvement in chronic obstructive airways disease is controversial. We measured left ventricular ejection fraction (LVEF) in 120 patients with severe chronic obstructive airways disease, 92 of them acutely decompensated and 28 stable. A bedside radionuclide technic using a scintillation probe was used to measure LVEF. Of the 28 patients with acute respiratory failure, LVEF was normal (larger than or equal to 55 per cent) in 60 and subnormal in 32. Of the 28 patients with stable chronic obstructive airways disease, LVEF was normal in 12 and low in 16. Coronary artery disease could be demonstrated clinically or at autopsy in 13 of the patients with acute and in 7 of the patients with stable chronic obstructive airways disease. LVEF was 28 plus or minus 10.4 per cent (average plus or minus SEM) in the patients with acute chronic obstructive airways disease and coronary artery disease which was significantly different (P smaller than 0.001) from LVEF in patients without coronary artery disease (61 plus or minus 1.9 per cent). In the patients stable with chronic obstructive airways disease and coronary artery disease, LVEF was (42 plus or minus 3.5 per cent), significantly different (P smaller than 0.001) from LVEF in those without coronary artery disease (55 plus or minus 2.1 per cent). There was no relationship between LVEF and arterial oxygen, or carbon dioxide tension, or pH. Results suggest that LVEF is normal in patients with severe lung disease alone and that reduced LVEF in patients with chronic obstructive airways disease can reasonably be ascribed to coronary artery disease.