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Biomedical subjects

L F Johnson

Publications and source records attributed to L F Johnson.

At least 181 records · Page 10Linked to original sources

Effects of vasoactive intestinal polypeptide (VIP) on lower esophageal sphincter in awake baboons: comparison with glucagon and secretin.

The effects of vasoactive intestinal polypeptide (VIP), glucagon, and secretin on lower esophageal sphincter pressure were investigated in awake baboons. The three hormones were compared with respect to effect on (1) resting lower esophageal sphincter pressure and (2) maximal stimulatory response to pentagastrin. VIP was shown to reduce resting and pentagastrin-stimulated lower esophageal sphincter pressure with significantly greater potency than either secretin or glucagon. For reduction of resting lower esophageal sphincter pressure, the potency ratio of VIP to secretin was 16:1 and of VIP to glucagon was 32:1 (P less than 0.05). For inhibition of pentagastrin-stimulated sphincter pressure, the potency ratio of VIP to secretin was 32:1 and of VIP to glucagon was 64:1 (P less than 0.02). This demonstration of significantly increased potency of VIP over known inhibitory hormones strengthens the suggestion that VIP may have a physiologic role in the control of lower esophageal sphincter function.

Animals↗

Esophageal emptying in achalasia quantitated by a radioisotope technique.

Delayed esophageal emptying of a radiolabeled meal distinguished symptomatic achalasia patients from asymptomatic controls. Esophageal emptying of the isotope meal significantly improved in ten achalasia patients after pneumatic dilation, and in one patient after surgical myotomy. The emptying curve in some patients after treatment simulated that of control subjects. Quantitation of esophageal emptying by a radiolabeled meal is a physiologic test that may be useful in evaluating results of therapy for achalasia.

Adult↗

Pulmonary aspiration as a consequence of gastroesophageal reflux: a diagnostic approach.

A radioisotope scintiscanning technique that can document pulmonary aspiration of gastric contents in patients with gastroesophageal reflux is described. Six patients with suspected nocturnal aspiration from reflux were studied. Three of the six had positive lung scans 8 hr after intragastric placement of 10 mCi of technetium 99m sulfur colloid. Overnight intraesophageal pH monitoring revealed prolonged episodes of GE reflux in those with positive scans. These preliminary observations suggest that this scintigraphic technique may be an effective method for documenting pulmonary symptoms as a consequence of gastroesophageal reflux.

Adult↗

Regulation of dihydrofolate reductase synthesis in an overproducing 3T6 cell line during transition from resting to growing state.

We have isolated a methotrexate (MTX)-resistant clone of mouse 3T6 cells, designated M50L3, which grows normally in the presence or absence of 50 muM MTX and produces a level of dihydrofolate reductase (DHFR; 5,6,7,8-tetrahydrofolate:NADP(+) oxidoreductase, EC 1.5.1.3) that is increased about 300-fold compared to the parental 3T6 cells. The cells retain the ability to rest in the G(0) state when maintained in medium containing 0.5% calf serum and can be stimulated to reenter the cell cycle by increasing the serum concentration to 10%. The rate of accumulation of DHFR in resting M50L3 cells is about 1/25th of that in exponentially growing cells. When resting cells are stimulated to reenter the cell cycle, the rate of accumulation of DHFR starts to increase at about 8 hr and reaches a maximum (25-fold increase) at about 16 hr after stimulation. Pulse-labeling experiments show that the increase in DHFR accumulation is due to an increased rate of synthesis. This increase occurs at about the same time the cells enter S phase. However, inhibitors of DNA synthesis have no effect on the increase in DHFR accumulation after serum stimulation, indicating that there is no tight coupling of the two events. Actinomycin D inhibits the subsequent increase in DHFR accumulation if added 8 hr after stimulation but has no effect if added 16 hr after stimulation. This is consistent with the idea that the increase in DHFR gene expression depends on transcription of the gene and that DHFR mRNA synthesis begins at about the time the cell initiates DNA replication. DHFR gene expression appears to be regulated in the same manner in the overproducing cells as we found in the parental 3T6 cells [Johnson, L. F., Fuhrman, C. L. & Wiedemann, L. M. (1978) J. Cell. Phys. 97, 397-406]. Therefore, the alterations that are responsible for DHFR overproduction (presumably DHFR gene amplification) do not interfere with the ability of the cell to regulate the rate of synthesis of the enzyme after serum stimulation.

Animals↗

Gastroesophageal reflux and pulmonary aspiration: incidence, functional abnormality, and results of surgical therapy.

The incidence of aspiration, the causative esophageal pathophysiology, and the results of surgical therapy were evaluated in 100 patients with abnormal gastroesophageal reflux documented by 24-hour esophageal pH monitoring. Based on historical evidence, 48 patients were suspected to be aspirators. Eight patients had documented episodes of aspiration (drop on esophagela pH, followed by acid taste in mouth and onset of cough or wheezing spell) during the monitoring period. Nine patients were considered to be potential aspirators because they presented oral acid regurgitation without development of pulmonary symptoms. In five patients a primary respiratory disorder (PRD) induced gastroesophageal reflux. The remaining 78 patients had abnormal reflux without aspiartion or regurgitation. Aspirators had a 75% incidence of esophageal motor abnormality on manometry, and the clearance of refluxed acid was significantly delayed in the supine position. A history of heartburn and endoscopic evidence of esophagitis were present in only half of the patients who were documented aspirators. Potential aspirators were spared from aspiration by rapid esophageal clearance of refluxed acid unaffected by changes in body position. Patients with a PRD had higher distal esophageal segment (DES) pressure and normal esophageal motility with minimal esophagitis. Nonaspirators significantly improved their clearance while in the supine position, emphasizing the protective effect of esophageal peristalsis against aspiration. An antireflux procedure in five aspirators raised the DES pressure significantly and returned the reflux status to normal by 24-hour pH-monitoring standards. The incidence of aspiration appears to be less than that suspected by history and is due to a motor disorder that interferes with the ability of the esophagus to clear reflex acid. Abnormal pulmonary symptoms can induce or result from gastroesophageal reflux and, when the latter occurs, an antireflex procedure stops both reflux and aspiration.

Cough↗

Evidence for highly stable nuclear poly(A) in cultured mammalian cells.

The kinetics of turnover of nuclear poly(A) were determined under conditions which facilitated the detection of relatively stable classes of the molecule. Growing 3T6 or HeLa cells were labeled with [3H]adenosine for several hours. The turnover of nuclear poly(A) was then followed over long time intervals using a variety of chase conditions. When a cordycepin chase was employed, a class of nuclear poly(A) with a half life of 2.5 h was observed. When the chase was effected by allowing the intracellular ATP pool specific activity to decay as a result of normal metabolic processes, a more stable class of nuclear poly(A) was detected (half life = 8--12 h). These results indicate that a significant portion of poly(A)-hnRNA has a long half-life.

Cell Line↗

Esophageal epithelial response to gastroesophageal reflux. A quantitative study.

Exposure of the distal esophageal mucosa to acid gastric juice was quantitated by 24-hr pH monitoring in 100 individuals and was correlated with morphologic data derived from esophageal biopsies. The degree of acid exposure to the distal esophagus correlated directly with increases in both relative and absolute length of the subepithelial papillae and to relative basal zone hyperplasia. Both papillary length and basal zone hyperplasia decreased after antireflux surgery had reduced acid exposure to normal. Reflux in the recumbent position resulted in prolonged exposure of the mucosa to acid because of poor acid clearing from the esophagus. This caused longer papillae than did upright reflux, where there were more frequent reflux episodes, but with rapid acid clearance. The presence of a hiatal hernia was associated with longer papillae, lower DES pressure, increased reflux frequency, and prolonged recumbent acid clearance. Twenty-four hour pH monitoring correlated better with papillary length than did symptoms or other clinical measures of gastroesophageal reflux.

Esophagus↗

Esophageal prosthesis in cancer.

We describe the use of polyvinyl esophageal prosthetic tubes to treat 14 consecutive patients with malignant strictures and tracheoesophageal fistula from carcinoma of the esophagus. We found these prosthetic tubes easy to construct, simple to insert, and that their use improved the quality of remaining life in most patients by diminishing dysphagia and incessant coughing from pulmonary aspiration.

Aged↗

Palliative dilation for dysphagia in esophageal carcinoma.

We retrospectively reviewed our experience with palliative dilation for dysphagia in esophageal carcinoma. During a 3-year period 26 patients with squamous-cell carcinoma of the esophagus underwent peroral esophageal dilation for relief of dysphagia. Twenty-four were able to resume a soft or regular diet after dilation. This improvement was accomplished with low morbidity and no mortality. Dilations were done without additional risk in patients with malignant tracheoesophageal fistulae and in patients undergoing radiation therapy. We conclude that esophageal dilation can be done safely and effectively in patients with squamous-cell carcinoma of the esophagus. Palliative dilation can significantly improve the quality of life for these patients and should be considered an important part of their management plan.

Carcinoma, Squamous Cell↗

Resistance of resting 3T6 mouse fibroblasts to methotrexate cytotoxicity.

We have compared the relative susceptibility of resting (GO) versus exponentially growing mouse fibroblasts (line 3T6) to methotrexate (MTX) cytotoxicity. Cultures of cells were exposed to different levels of MTX for various intervals. Cloning efficiencies of the cells were then determined in medium containing hypoxanthine and thymidine. We found that growing 3T6 cells exhibit time- as well as dose-dependent cytotoxicity. Greater than 95% of the cells were killed by a 24-hr exposure to 10(-6) M MTX. In contrast resting cells showed no loss of cloning efficiency even at drug concentrations of 10(-3) M and exposure times of 7 days. The resistance of resting cells is not the result of a MTX transport deficiency since extracellular MTX is taken up by both resting and growing cells. Furthermore, intracellular dihydrofolate reductase activity is abolished in both resting and growing cells at similar extracellular MTX dosages.

Cell Cycle↗