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Biomedical subjects

L F Johnson

Publications and source records attributed to L F Johnson.

At least 145 records · Page 8Linked to original sources
PubMed1984

Hiccups associated with reflux esophagitis.

A 67-yr-old man with protracted hiccups, as well as reflux esophagitis and a stricture, was found to have heartburn and water brash only during episodes of hiccups. Intraesophageal pH monitoring showed acid gastroesophageal reflux increased during these episodes and decreased with cessation of hiccups. After all attempts failed to relieve his hiccups, a Nissen fundoplication relieved heartburn, healed the esophagitis, and stopped excessive reflux of acid gastric juice, even though the hiccups persisted. These observations showed that reflux provoked by prolonged hiccups could either have adversely affected preexistent reflux esophagitis and stricture or conceivably could have caused these complications.

Aged↗
PubMed1983

Pill-induced esophageal injury. Case reports and review of the medical literature.

We report four cases of esophageal injury associated with the ingestion of commonly prescribed tablets or capsules. History and clinical characteristics of these cases suggest that the medications failed to transit the esophagus and acted locally to produce esophagitis. A search of English- and foreign-language medical journals documented 221 similar cases due to 26 different types of medication. While most of these esophageal injuries are self-limited and produce no morbidity beyond transient retrosternal pain, odynophagia, and dysphagia, major complications have occurred, such as mediastinal penetration, hemorrhage, and death. Patients should be counseled to take pills in an upright posture with liberal amounts of fluid well before retiring for the night.

Adult↗
PubMed1983

Tauroursodeoxycholic acid is less damaging than taurochenodeoxycholic acid to the gastric and esophageal mucosa.

Bile acids are capable of disrupting the gastric and esophageal mucosal barriers and are known to differ in their ability to injure these mucosae. Two bile acids, chenodeoxycholic and its 7-B epimer, ursodeoxycholic, that are being used to dissolve gallbladder stones were evaluated for their damaging effects on experimental preparations of the esophageal (rabbit) and gastric (dog) mucosa. Damage was assessed by measuring indices of mucosal barrier function, including net acid flux, potential difference, and tissue resistance, before and after exposure to the taurine conjugates of these bile acids. In both the esophageal and gastric mucosa, tauroursodeoxycholic acid caused significantly less disruption of barrier function than taurochenodeoxycholic acid. These results demonstrate that minor differences in conjugated bile acid structure can cause major changes in the effects of bile acids on the upper gastrointestinal mucosa and that ursodeoxycholic acid may be the preferred bile acid for oral ingestion to dissolve gallbladder stones.

Animals↗
PubMed1983

Barrett's esophagus: a review.

Barrett's esophagus may be defined as a columnar epithelium-lined distal esophagus. As a frequently recognized complication of gastroesophageal reflux, Barrett's esophagus has become a diagnosis of general clinical concern. Factors governing the development of this complication in patients with gastroesophageal reflux are unknown but may be congenitally determined in part. When symptoms are present, they are due to the complications of reflux, such as esophagitis, stricture, ulcer, or bleeding. Barrett's esophagus may be suspected on the basis of results of a barium meal test, endoscopy, or isotope scanning. Iodine staining at endoscopy or manometrically guided biopsy helps to localize the abnormal mucosal segment. The diagnosis is proved by biopsy. The columnar epithelium of Barrett's esophagus has a malignant predisposition, and, once the diagnosis is made, periodic endoscopy, with biopsy and cytologic study, is indicated. The treatment of Barrett's esophagus is directed toward objective cessation of gastroesophageal reflux. In refractory cases, antireflux surgery improves symptoms and complications from reflux, but the columnar epithelium generally persists along with its malignant potential. It is not known whether effective antireflux treatment will lower the incidence of adenocarcinoma.

Adenocarcinoma↗
PubMed1983

Effect of LiCl on gastric acid secretion and mucosal barrier function.

Lithium chloride (LiCl) has been shown to decrease gastric acid secretion and protect against ethanol-induced hemorrhagic gastritis in the rat. To further investigate these properties, two sets of experiments were performed in dogs with chronic Heidenhain pouches to study the effect of LiCl on histamine-stimulated gastric acid secretion and bile-induced disruption of the gastric mucosal barrier. In the first experiments the effect of LiCl on intravenous histamine-stimulated gastric secretion (40 micrograms/kg . hr) was determined. LiCl (30 mg/kg . hr) significantly reduced gastric acid secretion when compared to normal saline control (457 +/- 87 mueq H+/10 min versus 637 +/- 112 mueq H+/10 min, P less than 0.05). Serum and gastric lithium levels were determined and a significant inverse linear correlation existed between acid output and serum and gastric lithium levels. In the second set of experiments the effect of LiCl on bile-induced disruption of the gastric mucosal barrier was determined. Heidenhain pouches were continuously perfused with a pH 2 acid test solution and indices of mucosal barrier function (net acid back-diffusion and potential difference) were determined. LiCl (30 mg/kg . hr) significantly reduced both the increase in acid-back diffusion and the fall in potential difference with bile injury (5 mM taurodeoxycholate). In conclusion, these studies indicate that LiCl (1) decreases histamine-stimulated gastric acid secretion, and (2) diminishes bile-induced disruption of the gastric mucosal barrier in the canine Heidenhain pouch.

Animals↗
PubMed1983

Delayed processing of dihydrofolate reductase heterogeneous nuclear RNA in amino acid-starved mouse fibroblasts.

We have studied the metabolism of dihydrofolate reductase (DHFR) RNA in cells synchronized in the G1 phase of the cell cycle by starvation for isoleucine and glutamine. The relative content and stability of DHFR mRNA and the relative rate of transcription of the DHFR gene are similar in starved and exponentially growing cells. However, the relative rate of labeling of DHFR mRNA is about three times lower in starved cells than in exponentially growing cells. When the starved cells are stimulated to reenter the cell cycle by feeding them with complete medium, the relative rate of labeling of DHFR mRNA increases about fourfold within 6 h. However, the relative rate of transcription of the DHFR gene changes very little during this period. Continuous labeling experiments show that starved cells convert DHFR heterogeneous nuclear RNA into cytoplasmic DHFR mRNA much more slowly than serum-limited or exponentially growing cells. Pulse-chase experiments show that DHFR mRNA sequences contained in DHFR heterogeneous nuclear RNA appear to be conserved in starved cells. In addition, the content of DHFR RNA sequences in the nuclei of starved cells is about three times greater than that in exponentially growing cells. Delayed processing of DHFR heterogeneous nuclear RNA is also observed when exponentially growing cells are treated with inhibitors of protein synthesis. Our results suggest that, although delayed processing leads to a decrease in the initial labeling rate of DHFR mRNA, it does not result in a decrease in the actual rate of production of the message.

Amino Acids↗
PubMed1983

Regulation of histone mRNA production and stability in serum-stimulated mouse 3T6 fibroblasts.

We measured the content and metabolism of histone mRNA in mouse 3T6 fibroblasts during a serum-induced transition from the resting to growing state. The content of several histone H3 and H2b mRNAs was measured by an S1 nuclease procedure. All of these increase in parallel by a factor of about 50 during S phase. However, the rate of H3 gene transcription increased only fivefold during this period, as determined in an in vitro transcription assay. This suggests that histone mRNA content is also controlled at the posttranscriptional level. When resting cells were serum stimulated in the presence of cytosine arabinoside, the rate of H3 gene transcription increased to about the same extent as that in control-stimulated cells. However, cytoplasmic H3 mRNA content increased only five to seven-fold. The half-life of H3 mRNA during S phase was about 4 to 5 h. When cytosine arabinoside was added to cells in the S phase, the half-life of the message decreased to about 15 min. The rapid turnover of H3 mRNA was prevented when the drug was added in the presence of cycloheximide or puromycin. The rate of H3 gene transcription decreased by only 35% after treatment with cytosine arabinoside. These results suggest that H3 gene transcription is not tightly coupled to DNA replication but is controlled temporally during the resting to growing transition. However, there is a correlation between the rate of DNA synthesis and the stability of histone H3 mRNA.

Animals↗
PubMed1983

Alkaline esophagitis: a comparison of the ability of components of gastroduodenal contents to injure the rabbit esophagus.

Esophagitis is now recognized to occur in the absence of gastric acid. We have compared the potentially injurious effect of physiologic concentrations of trypsin, taurodeoxycholate, and pepsin at pH 7.5 using a continuously perfused rabbit esophagus model. Gross and microscopic esophagitis, tissue hemorrhage, and indexes of esophageal mucosal barrier function were assessed. Trypsin caused the most severe morphologic changes and hemorrhage, but only minimal disruption of the esophageal mucosal barrier. In contrast, taurodeoxycholate caused only minimal esophagitis and no hemorrhage, but caused extensive disruption of the esophageal mucosal barrier. Neither pepsin, at this alkaline pH, nor alkaline test solution alone (pH 7.5) caused esophageal injury by any criteria. These results show that the degree of esophageal mucosal barrier disruption cannot always be equated with the degree of morphologic injury, and that different components of the gastroduodenal contents may differ in their sites or mechanisms of esophageal injury. Finally, among the gastroduodenal contents we tested, trypsin was the most noxious agent in alkaline reflux esophagitis in terms of causing mucosal erosion, inflammation, and hemorrhage.

Animals↗
PubMed1983

Evaluation of in vivo measurement of transesophageal electrical resistance as an indicator of early experimental esophageal mucosal injury.

Experimental esophageal mucosal injury has been characterized by an increase in mucosal permeability to acid and a fall in transmucosal electrical potential difference (PD). We have developed a technique for measuring transesophageal electrical resistance in an in vivo rabbit model of esophageal injury and have performed experiments to assess this parameter as an index of esophageal injury. As expected, tissue resistance varied inversely with mucosal area. The current-voltage plot for the esophagus with or without trypsin, bile, or acid injury remained linear with no "breakpoints." Tissue resistance was compared with standard indices of mucosal injury such as acid flux, PD, and morphologic change in experimental esophageal injury due to acid, bile, and trypsin. Our results show that tissue resistance is more sensitive than either PD or acid flux in detecting early esophageal injury due to low concentrations of acid or trypsin and, as opposed to PD, always showed a persistent, unidirectional change with injury. Thus these data show that in vivo measurement of transesophageal electrical resistance is a useful technique for assessing esophageal mucosal injury, in that it is the most sensitive indicator of esophageal injury we have observed.

Animals↗
PubMed1982

Regulation of dihydrofolate reductase gene transcription in methotrexate-resistant mouse fibroblasts.

We have used a methotrexate-resistant mouse 3T6 cell line (M50L3) that overproduces dihydrofolate reductase (DHFR) and its mRNA by a factor of about 300 to study the regulation of DHFR hnRNA synthesis. We have previously shown that when resting (G0) M50L3 cells are serum stimulated to reenter the cell cycle, the amount and rate of synthesis of DHFR and the content of DHFR mRNA all begin to increase as the cells enter the S phase of the cell cycle. The increase in DHFR mRNA content is due to an increase in the rate of mRNA production. In the presnt study, we have used the technique of DNA-excess filter hybridization to determine the rate of synthesis of DHFR hnRNA relative to total hnRNA at various times following serum stimulation. We found that the relative rate of DHFR hnRNA synthesis began to increase at about the same time (6 hours), and increased to about the same extent (three to fourfold by 15 hours following stimulation) as we observed previously for DHFR mRNA production. This suggests that the increase in DHFR mRNA production (and consequently DHFR gene expression) is controlled primarily, if not exclusively, at the level of transcription. We also studied the effect of addition of high concentrations of dibutyryl cAMP and theophylline on DHFR gene transcription. We found that addition of these drugs at the time of stimulation completely blocked the increase in DHFR hnRNA synthesis as well as entry into S phase. Addition of the drugs at either 13 or 20 hours following stimulation led to a rapid decrease in DHFR hnRNA synthesis. The drugs were found to have little effect on the ability of the cells to complete S phase when they were added at 13 hours following stimulation. Our results suggest that high intracellular concentrations of cAMP may affect DHFR gene expression not only by preventing the progression of cells through the G1 phase of the cell cycle but also by affecting the rate of DHFR gene transcription in a more direct manner.

Animals↗
PubMed1982

Interaction of lower esophageal sphincter pressure and length of sphincter in the abdomen as determinants of gastroesophageal competence.

This study defines the components of distal esophageal sphincter function which predict gastroesophageal competence and examines the mechanisms by which three antireflux procedures restore competence to the cardia. In a prospective study, the reflux status of 391 patients was determined by 24 hour pH monitoring. Distal esophageal sphincter pressure and length of sphincter exposed to the positive pressure environment of the abdomen was measured by esophageal infusion manometry. Similar pre- and postoperative studies were performed in 45 patients who were randomized to three equal groups for the Hill, Belsey and Nissen antireflux procedures. Two hundred sixty-seven (68 percent) of the 391 patients had a positive 24 hour pH test. Competence of the cardia was related to pressure in the distal esophageal sphincter, to the length of sphincter in the abdomen and to an interaction between both (all p less than 0.05). Thus, competence of the cardia requires an adequate pressure and length of sphincter in the abdomen. In determining competence, the pressure and length effects are not additive, but have an interacting relationship. Sphincter pressure and abdominal length are independently corrected by surgery. Restoration of competence requires increases in both. The gastric fundic wrap best augments distal esophageal sphincter pressure by application of normal functioning smooth muscle to the lower esophagus. Sphincter dynamics are normal after a wrap as the gastric fundus and distal esophageal sphincter share the functions of synchronous contractions and simultaneous relaxation on deglutition.

Esophagogastric Junction↗
PubMed1982

Endoscopic foreign body retrieval through a gastrostomy feeding orifice.

This report concerns the removal of a dental bridge through a feeding gastrotomy orifice under direct endoscopic visualization. A 90-year-old bedridden female with a feeding gastrostomy tube, dislodged and swallowed her dental bridge during a coughing episode. At upper endoscopy the dental bridge was snared in the stomach but removed with a pair of Kelly clamps through the feeding gastrostomy orifice. The removal technique ad a discussion of our management alternatives are presented.

Aged↗
PubMed1982

Regulation of ribosomal protein mRNA content and translation in growth-stimulated mouse fibroblasts.

When resting (G0) mouse 3T6 fibroblasts are serum stimulated to reenter the cell cycle, the rates of synthesis of rRNA and ribosomal proteins increase, resulting in an increase in ribosome content beginning about 6 h after stimulation. In this study, we monitored the content, metabolism, and translation of ribosomal protein mRNA (rp mRNA) in resting, exponentially growing, and serum-stimulated 3T6 cells. Cloned cDNAs for seven rp mRNAs were used in DNA-excess filter hybridization studies to assay rp mRNA. We found that about 85% of rp mRNA is polyadenylated under all growth conditions. The rate of labeling of rp mRNA relative to total polyadenylated mRNA changed very little after stimulation. The half-life of rp mRNA was about 11 h in resting cells and about 8 h in exponentially growing cells, values which are similar to the half-lives of total mRNA in resting and growing cells (about 9 h). The content of rp mRNA relative to total mRNA was about the same in resting and growing 3T6 cells. Furthermore, the total amount of rp mRNA did not begin to increase until about 6 h after stimulation. Since an increase in rp mRNA content did not appear to be responsible for the increase in ribosomal protein synthesis, we determined the efficiency of translation of rp mRNA under different conditions. We found that about 85% of pulse-labeled rp mRNA was associated with polysomes in exponentially growing cells. In resting cells, however, only about half was associated with polysomes, and about 30% was found in the monosomal fraction. The distribution shifted to that found in growing cells within 3 h after serum stimulation. Similar results were obtained when cells were labeled for 10.5 h. About 70% of total polyadenylated mRNA was in the polysome fraction in all growth states regardless of labeling time, indicating that the shift in mRNA distribution was species specific. These results indicate that the content and metabolism of rp mRNA do not change significantly after growth stimulation. The rate of ribosomal protein synthesis appears to be controlled during the resting-growing transition by an alteration of the efficiency of translation of rp mRNA, possibly at the level of protein synthesis initiation.

Animals↗
PubMed1982

Thymidylate synthetase overproduction in 5-fluorodeoxyuridine-resistant mouse fibroblasts.

We describe the isolation and characterization of a series of 5-fluorodeoxyuridine (FdUrd)-resistant mouse 3T6 cell lines that overproduce thymidylate synthetase (TS) by up to 50-fold compared with the parental cells. The resistant cells were selected by growing 3T6 cells or a methotrexate-resistant 3T6 cell line (M50L3, isolated previously in our laboratory) in gradually increasing concentrations of FdUrd. Uridine and cytidine were included in the culture medium to reduce toxicity from metabolic products of FdUrd. Cells that were resistant to the drug by virtue of loss of thymidine kinase activity were eliminated by selection in medium containing hypoxanthine, methotrexate, and thymidine. M50L3 cells were found to adapt to FdUrd more readily than 3T6 cells. A number of clones were isolated that were able to grow in the presence of 3 microM (M50L3 derived) or 0.3 microM (3T6 derived) FdUrd. Several were found to overproduce TS by 10 to 50-fold compared with normal 3T6 cells. All were found to have thymidine kinase activity, although the enzyme level was significantly reduced in some clones. The overproduced TS was inactivated by 5-fluorodeoxyuridylic acid at the same concentration as the enzyme from 3T6 cells. TS was purified from the LU3-7 clone (50-fold overproducer) by affinity chromatography on methotrexate-polyacrylamide. The monomer molecular weight was about 38,000, which was the same as the molecular weight of the monomer in 3T6 cells. The overproduction trait was gradually lost (half-life, 3 weeks) when LU3-7 cells were grown in the absence of FdUrd. The overproducing cells will provide an abundant supply of TS and (very likely) its mRNA and may serve as a convenient model system for detailed studies of the regulation of TS gene expression during the cell cycle.

Animals↗
PubMed1982

Role of the components of the gastroduodenal contents in experimental acid esophagitis.

Esophagitis has been associated with the reflux of acidic gastroduodenal contents. These contents may contain not only HCl but also pepsin, bile, and pancreatic enzymes. This experiment was designed to compare the roles of these components in experimental acid esophagitis. The esophagus of the rabbit was cannulated and perfused continuously via a recirculating system with pH 2 acid test solution. Net flux of H+, K+, glucose, and hemoglobin plus the recovery of tritiated water were determined before and after the addition of pepsin, taurodeoxycholate, or trypsin. Afterward the esophageal segments were graded for gross and microscopic esophagitis. These studies show that pepsin caused significant gross and microscopic esophagitis. Moreover, pepsin also caused significant increases in H+, K+, glucose, and hemoglobin flux as well as decreased recovery of tritiated water. Taurodeoxycholate increased esophageal mucosal permeability to H+, K+, and glucose and decreased the recovery of tritiated water but did not cause significant pathologic change. Trypsin and acid alone did not result in significant esophagitis by either pathologic or ionic permeability criteria. These results show tha disruption of the esophageal mucosal barrier cannot be equated with pathologic injury and that different components of the gastroduodenal contents may have different sites or mechanisms of injury.

Animals↗