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Biomedical subjects

L F Johnson

Publications and source records attributed to L F Johnson.

At least 109 records · Page 6Linked to original sources
PubMed1988

Saliva: its role in health and disease.

Saliva serves many functions in the upper digestive tract, with its roles in esophageal physiology, digestion, and gastric cytoprotection having been documented by many studies in the recent literature. Understanding the multiple functions of saliva and the consequences of its absence is of paramount importance to gastroenterologists. We present a clinically oriented review of the literature on the role of saliva in the upper gastrointestinal tract and review the many problems associated with lack of saliva. We also discuss the management of xerostomia.

Digestion↗
PubMed1987

Gastric emptying of solid food in patients with gastroesophageal reflux.

While delayed gastric emptying of solid food has been reported in patients with symptoms of gastroesophageal reflux, the study populations were not defined by 24-h intraesophageal pH monitoring. Moreover, the influence that the gastric emptying rate may have on patterns of reflux during the day or night, as well as on esophagitis, is not known. In this study, we compared the gastric emptying rate of solid food (in vivo intracellular labeled chicken liver) observed in asymptomatic control volunteers (n = 15) with that of symptomatic patients with an abnormal 24-h pH record who had either the presence (n = 22) or absence (n = 11) of endoscopic esophagitis. We found no significant difference in the gastric emptying rate between the asymptomatic control volunteers and the symptomatic patients with and without esophagitis. Moreover, there was no significant correlation between the gastric emptying rate and the degree of daytime or nighttime distal esophageal acid exposure found during 24-h intraesophageal pH monitoring. Only 6% of the symptomatic patients had a gastric emptying rate that exceeded the mean value plus 2 SD of that found in the asymptomatic control volunteers. We believe these support a de-emphasis of the role that delayed gastric emptying of solid food may play in the pathophysiology of gastroesophageal reflux in most patients.

Adult↗
PubMed1987

Serum creatine kinase and lactate dehydrogenase isoenzyme levels in patients after major esophageal surgery, esophageal dilation, and acute myocardial infarction.

All three isoenzymes of creatine kinase (CK), including MB, the fraction used in diagnosing acute myocardial infarction (AMI), have been found in the esophagus. Clinical reports suggest that injuries to the esophagus can cause changes in peripheral serum CK. This prospective study was designed to delineate whether esophageal dilation or major esophageal surgery would cause changes in serum CK and lactate dehydrogenase isoenzymes that might be consistent with the diagnosis of an AMI. Two groups of patients admitted to a coronary care unit were used as controls: patients with electrocardiographically proved AMI and those who had chest pain but who had AMI ruled out by sequential electrocardiograms. The coronary care unit patients had serum enzymes determined on admission, then every 8 hours for four samples, and then daily for 3 days. The surgical patients had determinations preoperatively, in recovery, every 8 hours for four samples, and daily for 5 days. The patients who had esophageal dilations had serum enzyme levels drawn before the procedure and every 8 hours for 2 days after dilation. Serum total CK and lactate dehydrogenase levels were determined by automated spectrophotometry. Isoenzyme levels were determined by agarose gel electrophoresis. The data suggest that small serum CK-MB bands that may be generated by esophageal surgery or dilation can be differentiated from those seen in AMI and that AMI can be confirmed by simultaneous analysis of serum lactate dehydrogenase isoenzymes.

Clinical Enzyme Tests↗
PubMed1987

The effect of terbutaline sulfate, nitroglycerin, and aminophylline on lower esophageal sphincter pressure and radionuclide esophageal emptying in patients with achalasia.

We studied the effects of three smooth muscle relaxants on lower esophageal sphincter (LES) pressure and radionuclide esophageal emptying in 15 untreated patients with achalasia. LES pressures were determined before and after the administration of normal saline subcutaneously, terbutaline sulfate subcutaneously, nitroglycerin sublingually, and aminophylline intravenously. All smooth muscle relaxants significantly decreased LES pressures when compared with normal saline controls and pretreatment baseline pressures (p less than 0.01). However, in normal saline controls, LES pressure actually increased over time (p less than 0.01). Control radionuclide esophageal emptying studies were performed in all patients. Subsequent esophageal emptying studies were carried out only in patients responding to smooth muscle relaxants by decreasing LES pressures by greater than or equal to 25% (terbutaline sulfate, n = 8; nitroglycerin, n = 7; and aminophylline, n = 4). Significant improvement in esophageal emptying was observed after nitroglycerin and terbutaline sulfate (p less than 0.05) but not after aminophylline. We conclude that in patients with achalasia (a) terbutaline sulfate, nitroglycerin, and aminophylline can significantly decrease LES pressure; (b) resting LES pressures vary over time; and (c) terbutaline sulfate and nitroglycerin significantly improve esophageal emptying in some subjects.

Adult↗
PubMed1986

Structure of the gene for mouse thymidylate synthase. Locations of introns and multiple transcriptional start sites.

We have isolated and analyzed the structure of the gene for thymidylate synthase from a 5-fluoro-2'-deoxyuridine-resistant 3T6 cell line that overproduces thymidylate synthase 50-fold by virtue of gene amplification. Three overlapping DNA segments containing the entire thymidylate synthase gene were identified in Charon 35 genomic libraries. Sequence analysis revealed that all of the coding regions were contained in a 12-kilobase segment of DNA. The gene has 6 introns ranging from 0.6 to 4.1 kilobases in length. The sequences at the 5' and 3' ends of each intron conformed to the consensus sequences for mammalian introns. S1 nuclease and primer extension assays showed that transcription of the thymidylate synthase gene initiates at several sites within a 66-nucleotide region. There are no TATAA or CCAAT sequences in the vicinity of the initiation sites. However, the region does contain DNA sequences that are known to stimulate binding of the transcription factors Sp1 and USF. These binding sites are adjacent to each other, suggesting that the two proteins may bind to the upstream region of the thymidylate synthase gene in a cooperative or competitive manner.

Animals↗
PubMed1986

Gastrointestinal blood loss associated with running a marathon.

Gastrointestinal bleeding has been observed in long-distance runners. We prospectively studied participants of the Eighth Annual Marine Corps Marathon to determine the incidence of gastrointestinal blood loss associated with long-distance running. Of 600 runners contacted, 125 (21%) returned a questionnaire as well as pre- and postmarathon stool specimens. Stool specimens converted from Hemoccult negative to positive in 29/125 (23%) of the participants, indicating that running the marathon was associated with gastrointestinal blood loss (P less than 0.001). The incidence of this conversion (negative to positive) was significant for both males (N = 68, P less than 0.001) and females (N = 57, P less than 0.05). Gastrointestinal bleeding appeared to be independent of age, race time, abdominal symptoms, and the recent ingestion of aspirin, vitamin C, or steak.

Adult↗
PubMed1986

Mouse thymidylate synthase messenger RNA lacks a 3' untranslated region.

Analysis of the sequence of cDNA corresponding to mouse thymidylate synthase (5,10-methylenetetrahydrofolate:dUMP C-methyltransferase, EC 2.1.1.45) mRNA revealed that the termination codon TAA was followed immediately by a poly(A) sequence. This raised the possibility that mouse thymidylate synthase mRNA lacks a 3' untranslated region. In the present study, we have further investigated this possibility. DNA corresponding to the 3' end of the thymidylate synthase gene was isolated from a genomic library. The sequence of the genomic DNA was identical to that of the cDNA in the coding region. However, the termination codon was TAG in the genomic sequence rather than TAA, and poly(A) was not present in the genomic DNA. Sequences flanking the site of poly(A) addition were in good agreement with polyadenylylation consensus sequences. S1 nuclease analysis revealed that approximately 80% of the thymidylate synthase mRNA molecules were polyadenylylated at the termination codon. A secondary polyadenylylation site was detected 190-200 nucleotides downstream of the primary site. We conclude that the major species of mouse thymidylate synthase mRNA lacks a 3' untranslated region and that the final A of the termination codon is added by poly(A) polymerase. It appears that a 3' untranslated region is not essential for the accumulation or translation of this mRNA.

Animals↗
PubMed1986

Sequence of a cDNA for mouse thymidylate synthase reveals striking similarity with the prokaryotic enzyme.

We report the nucleotide sequence of a cloned cDNA, pMTS-3, that contains a 1-kb insert corresponding to mouse thymidylate synthase (E.C. 2.1.1.45). The open reading frame of 921 nucleotides from the first AUG to the termination codon specifies a protein with a molecular mass of 34,962 daltons. The predicted amino acid sequence is 90% identical with that of the human enzyme. The mouse sequence also has an extremely high degree of similarity (as much as 55% identity) with prokaryotic thymidylate synthase sequences, indicating that thymidylate synthase is among the most highly conserved proteins studied to date. The similarity is especially pronounced (as much as 80% identity) in the 44-amino-acid region encompassing the binding site for deoxyuridylic acid. The cDNA sequence also suggests that mouse thymidylate synthase mRNA lacks a 3' untranslated region, since the termination codon, UAA, is followed immediately by a poly(A) segment.

Amino Acid Sequence↗
PubMed1986

Experimental esophagitis in a rabbit model. Clinical relevance.

Esophagitis occurs in patients with excessive acid and/or alkaline gastroesophageal reflux. This observation prompted us to develop a continuously perfused in vivo rabbit esophageal model to examine the potential for different endogenous injurious agents to cause H+ back diffusion and morphologic evidence of esophagitis. We found that HCl at physiologic pH values did not break the mucosal barrier to H+ back diffusion or cause esophagitis. Bile salts at physiologic concentrations in both an acid or alkaline perfusate broke the mucosal barrier and caused H+ back diffusion, but failed to cause a morphologic injury consistent with clinical reflux esophagitis. Instead, proteolytic enzymes, such as pepsin in an acid environment and trypsin in an alkaline environment, caused a severe hemorrhagic erosive esophagitis consistent with that seen clinically. We feel new therapeutic strategies for the treatment of reflux esophagitis should be directed at proteolytic enzymes rather than only HCl or bile salts. Finally, we showed sucralfate to be a mucosal protectant against the acid-pepsin injury.

Animals↗
PubMed1986

Development of the 24-hour intraesophageal pH monitoring composite scoring system.

We describe in detail our logic for deriving a system to score 24-hour intraesophageal pH records of patients with gastroesophageal reflux. This system uses a uniform scoring unit and pH monitoring parameters taken from both the day and nighttime segments of the pH record. The score quantitates the degree of departure that a patient's reflux pattern exceeds physiologic reflux found in asymptomatic control volunteers, and directly correlates with the degree of reactive epithelial change characteristic of reflux esophagitis. Even though the scoring system was derived over 11 years ago, its logic and scoring principles are consistent with new concepts that concern the pathophysiology of gastroesophageal reflux disease.

Eating↗
PubMed1986

Rumination, heartburn, and daytime gastroesophageal reflux. A case study with mechanisms defined and successfully treated with biofeedback therapy.

A 31-year-old man with a 19-year history of rumination developed frequent episodes of heartburn and regurgitation associated with acid gastroesophageal reflux that occurred predominantly during the day. This reflux and its attendant symptoms resulted from abdominal muscle contractions at the time of gastroesophageal pressure equilibration (i.e., common cavity phenomena) consistent with the egress of air from the stomach to the esophagus. A voluntary pharyngeal maneuver unassociated with swallowing but simultaneous with the abdominal contraction resulted in a decrease in upper esophageal sphincter pressure. This lowered pressure facilitated acid esophagopharyngeal regurgitation at a velocity of 100 cm/s. Biofeedback therapy directed at relaxing the abdominal muscles during eating and avoiding the pharyngeal maneuver resulted in a decrease in reflux and marked improvement in symptoms.

Adult↗
PubMed1985

Regulation of thymidylate synthase enzyme synthesis in 5-fluorodeoxyuridine-resistant mouse fibroblasts during the transition from the resting to growing state.

Thymidylate synthase (TS) activity is very low in resting mouse 3T6 fibroblasts but increases sharply in growth-stimulated cells at about the same time the cells enter S phase. To study the mechanism responsible for the increase in TS level, we isolated a 5-fluorodeoxyuridine (5-FdUrd)-resistant cell line (LU3-7) that overproduces TS and its mRNA about 50-100-fold. In this paper we show that the LU3-7 cells were able to rest in the G0 state of the cell cycle when maintained in medium containing 0.5% serum. When the serum concentration was increased to 10%, the resting cells reentered the cell cycle and began DNA replication about 12 hr later. TS activity remained at the resting level until DNA replication began, then increased at later times. The increase was not affected when the cells were stimulated in the presence of DNA synthesis inhibitors. The rate of synthesis of TS (as determined in a pulse-labeling experiment) remained at the resting level for the first 10 hr following stimulation, then increased 8-9-fold by 25 hr following serum stimulation. The half-life of TS in growing LU3-7 cells was measured in a pulse-chase experiment and found to be greater than 24 hr. Therefore the increase in TS activity was primarily due to an increase in the rate of synthesis of the enzyme. Since TS gene expression appears to be regulated in a similar manner in LU3-7 cells and in the parental 3T6 cells, the LU3-7 cells should be a good model system for detailed analysis of the mechanism for regulating TS gene expression in mammalian cells.

Animals↗
PubMed1985

Hemobilia and liver flukes in a patient from Thailand.

A patient from Southeast Asia presented with abdominal pain, fever, jaundice, and upper gastrointestinal bleeding of unknown origin. Opisthorchis viverrini eggs were found in the stool and multiple hepatic filling defects were noted on liver scan and sonogram. Endoscopic retrograde cholangiopancreatography revealed cholelithiasis and crescent-like filling defects in the biliary system. At surgery, the gallbladder was filled with clotted blood and pigmented stones. During T-tube drainage of the common bile duct, small elliptical flukes (4 X 3 mm) identified as O. viverrini were recovered. Despite adequate biliary drainage, the patient continued to have high fevers. On the 53rd postoperative day, a larger fluke (2.8 X 0.8 cm) identified as a Fasciola hepatica migrated down the T-tube. Institution of therapy with bithional resulted in complete clinical resolution within 3 wk. Six years later the patient returned with fever, jaundice, and right upper quadrant pain. Two large pigmented stones were found in the common bile duct and were removed after endoscopic sphincterotomy. The stones had developed even though there was no evidence of recurrent helminthic infection.

Adult↗
PubMed1985

Sucralfate prevents experimental peptic esophagitis in rabbits.

Sucralfate was tested in a rabbit model for its ability to prevent experimental esophagitis. Esophagitis was assessed by gross appearance and microscopic examination by an uninformed observer. In addition, the permeability of the esophagus to a number of probe molecules was measured to assess barrier function. Animals were exposed for 1 h to either acid alone (HCl at pH 2), acid plus pepsin (0.8 mg/ml), or acid plus taurocholic acid (5 mM), as well as to the same injurious agents with the addition of 1 g of sucralfate. At the completion of this hour, the perfusate was removed and all animals were again perfused for 1 h with HCl at pH 2 while mucosal permeability was assessed by measuring erythritol, glucose, potassium, and sodium fluxes. The animals were then killed. Sucralfate significantly diminished esophagitis and the attendant mucosal permeability changes induced by pepsin. The viscous sucralfate gel was shown to adhere tenaciously to the esophageal mucosa, but this characteristic of sucralfate was found not to be critical for its protective action because a clear sucrose sulfate solution with no gel present was also protective. Hence, it was not necessary for the gel to be present for the drug to be effective. Several in vitro tests suggested that the clear sucrose sulfate solution, like the sucralfate gel, probably acts through a topical protectant effect, rather than through pepsin inactivation. Although the degree of esophagitis induced by the bile acid was significantly less than that observed with pepsin, the mucosal permeability changes were comparable. Sucralfate did not significantly reduce the flux rates of glucose, potassium, and sodium nor did it affect the morphology of the mucosa after exposure to taurocholic acid. In conclusion, the binding of sucralfate to pepsin substrates in tissue results in this agent being very effective in preventing experimental peptic esophagitis.

Aluminum↗