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C A Lucas

Publications and source records attributed to C A Lucas.

25 records · Page 2Linked to original sources

Regulation of acetylcholinesterase secretion from neuronal cell cultures.--1. Actions of nerve growth factor, cytoskeletal inhibitors and tunicamycin.

The release of enzymatically active acetylcholinesterase was measured from two types of neuronal cell cultures. Evidence is presented that primary cultures of chick optic lobe and clonal rat PC12 cells released acetylcholinesterase by similar mechanisms. The secretion was selective for the tetrameric or larger molecule forms of acetylcholinesterase. Thus the chick primary cultures released the so-called G4 isoenzyme of acetylcholinesterase. The rat PC12 cells, after pretreatment with nerve growth factor, secreted mainly G4 acetylcholinesterase and a small amount of an isoenzyme sedimenting at 16S. The rate of secretion of acetylcholinesterase was regulated by the three types of agents used. (1) Acetylcholinesterase secretion was markedly increased by nerve growth factor. (2) Microtubule inhibitors (colchicine, taxol and nocodazole) suppressed the rate of release of acetylcholinesterase. (3) Acetylcholinesterase release was also decreased by an inhibitor of protein glycosylation, tunicamycin. We provide evidence that these three types of agents regulate acetylcholinesterase secretion not by a direct effect on secretion, but by modulatory effects on the synthesis, intracellular transport and turnover of the enzyme. (1) Nerve growth factor acts on acetylcholinesterase secretion via increased synthesis of messenger RNA. (2) Microtubule inhibitors act by preventing intracellular transport. (3) Tunicamycin acts by decreasing the intracellular activity of acetylcholinesterase, possibly via enhanced proteolytic breakdown.

Acetylcholinesterase↗

Regulation of acetylcholinesterase activity by retinoic acid in a human neuroblastoma cell line.

The ability of retinoic acid (RA) to modulate acetylcholinesterase (AChE) activity in a human neuroblastoma cell line (LN-N-5) was examined. The specific activity of AChE was significantly increased 3 days after exposure of LA-N-5 to RA and reached its maximum values after 9 or more days of culturing. Dose-response experiments demonstrated that large increases of AChE occurred at RA concentrations between 10(-7) and 10(-6) M with maximum AChE values detected at 10(-6)-10(-5) M. Increased AChE activity paralleled neurite outgrowth in LA-N-5 cultures. These findings demonstrate that RA can regulate specific AChE activity in human neuroblastoma cells in a manner consistent with neuronal maturation.

Acetylcholinesterase↗

Induction of fiber outgrowth in PC12 pheochromocytoma cells by a neuronotrophic factor occurring in human tumors.

Human tumors contain one or several factors which induce fiber outgrowth in a clonal cell line of rat adrenal medullary pheochromocytoma. Its action was tested semiquantitatively in cultured PC12 pheochromocytoma cells using conditioned media from cultures of 45 different brain tumors and homogenates of 18 human tumors of brain and non-brain origin. All tumor homogenates investigated and 71% of the conditioned media were active. The stimulation of fiber growth and the morphological appearance of neurites resembled that seen after treatment with the nerve growth factor (NGF). However, experiments with NGF antiserum and with an NGF non-responsive PC12-mutant indicated that the neuronotrophic factor(s) occurring in human tumors are different from NGF. The active factor is heat labile, unstable at pH's below 4, but stable up to pH9. It retains its activity after dialysis.

Adrenal Gland Neoplasms↗

Regulation of acetylcholinesterase by nerve growth factor in the pheochromocytoma PC12 cell line.

In the PC12 clonal nerve cell line derived from a rat pheochromocytoma, the activity of acetylcholinesterase (AChE) is regulated by nerve growth factor (NGF). The specific activity of AChE was significantly increased 2 days after exposure of PC12 cells to NGF (8 X 10(-8) M), and reached its maximal increase of 94% after 3 days. Thereafter the specific activity of AChE did not significantly vary during the following 7 days. AChE cytochemistry showed the enzyme activity to be localized predominantly in cisternae of the rough endoplasmic reticulum, with a strongly enhanced activity after NGF treatment.

Acetylcholinesterase↗

Factors in the physician practice location puzzle: a survey of New York State residency-trained family physicians.

BACKGROUND: For the past 5 years fewer medical students have selected primary care specialties, and one-third of all physicians have indicated they will move in the next 5 years. These two factors make family physicians one of the most recruited specialties in medicine. METHODS: A questionnaire about practice profiles and factors that have an impact on a physician's location decision was mailed to all physicians who graduated from New York State family medicine residencies between 1970 and 1989. Data from completed responses were analyzed by year of graduation from residency, community size, and whether the responder remained in New York State or chose to locate outside New York State. RESULTS: There were 711 (46 percent) physicians who responded. The number of minorities remained stable at 14 percent during these years, but women graduates increased from 12 percent to 21 percent. The graduates in the 1980s, when compared with those in the 1970s, were more likely to be salaried, make less money, and to believe employment for the physician's spouse to be important in practice location. The 38 percent of responders from communities of fewer than 25,000 were less likely to be salaried, were more likely to practice in a group, worked more hours, offered a broader range of services including obstetrics, made less money, and placed less importance on availability of hospital consultants. Extended family, previous negotiated obligations, and geographic or climate issues were the reasons 64 percent of out-of-state responders gave for leaving New York. Spouse's opinion, hospital consultants, hospital services, colleague interaction, and after-hours coverage were most frequently rated as important factors for family physician practice location. CONCLUSIONS: Factors important in attracting new physicians to a community include the spouse's opinion, institutional and colleague support, and lifestyle issues.

Adult↗

Audit of the investigation and outcome of iron-deficiency anaemia in one health district.

The investigation of iron-deficiency anaemia (IDA) is a clinical problem which arises in virtually all branches of medicine. To audit the investigation of IDA, a computer-based laboratory record system was used to identify all women over 50 years of age and all men (n = 200) presenting to a single district laboratory with probable IDA in a six-month period. In 21 of 130 incident cases anaemia was clearly attributable to non-gastrointestinal disease. Of the remaining 109, 19% had investigation of both upper and lower gastrointestinal tract, 21% the upper gastrointestinal tract only, and 7% the lower gastrointestinal tract only. In 55 cases either no investigation was performed or only faecal occult blood tests. Eighteen months after presentation nine colorectal cancers, five gastric cancers and 11 peptic ulcers had been diagnosed; 21 patients had died, including two from colorectal cancers not detected when the IDA presented. This audit has revealed substantial underinvestigation of probable IDA, with serious but treatable conditions remaining undetected. Our findings, which we have no reason to believe are unrepresentative, indicate that policies are needed to ensure adequate investigation of IDA.

Aged↗