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Biomedical subjects

D E Larson

Publications and source records attributed to D E Larson.

At least 55 records · Page 3Linked to original sources

Down-regulation of histone H3 and H4 gene transcription in differentiated L6 myotubes.

The core histone mRNA levels in terminally differentiated L6 myotubes decrease to less than 5% of the amount present in proliferating myoblasts in parallel with the cessation of DNA synthesis (Bird, RC., Jacobs, F.A., Stein, G., Stein, J. and Sells, B.H. (1985) Biochim. Biophys. Acta 824, 209-217). The role of gene transcription in the down-shift of histone mRNA levels was assessed using a cell-free system. The level of transcription from the differentiation-independent adenovirus major late promoter was directly related to the RNA polymerase II activity of myoblast and myotube nuclear extracts. In addition, both extracts actively transcribed the histone H4 gene template containing only the 5 proximal promoter region (-210 bp). In contrast, inclusion of the distal-proximal promoter region (-410 to -210 bp) in the template resulted in a 60% decrease in transcription by the myotube extract. A similar down-shift in transcription of the histone H3 gene template (containing 900 bp 5 of the initiation site) by myotube nuclear extracts was also observed. The decrease in histone mRNA levels in myotubes may therefore be controlled in part by a transcriptional mechanism involving a negative regulatory factor.

Animals↗

Risk for colorectal adenocarcinoma in pernicious anemia. A population-based cohort study.

STUDY OBJECTIVE: To determine the long-term risk for colorectal cancer among patients with pernicious anemia. DESIGN: Historical cohort study. SETTING: Population-based inception cohort of Rochester, Minnesota, residents. PATIENTS AND METHODS: We identified 150 Rochester residents who had the onset of pernicious anemia during the 30-year period from 1950 through 1979, and we followed this cohort for 1664 person-years of observation. The observed risk for subsequent colorectal cancer in the cohort was compared with that expected based on incidence rates of colon and rectal cancer for the local population. MEASUREMENTS AND MAIN RESULTS: There were 14 cases of colorectal cancer among the 150 patients with pernicious anemia (where 10.5 cases were expected), and 9 of these cases were found after the diagnosis of pernicious anemia was established (where 5.1 cases were expected). The relative risk for colon cancer at any time after the diagnosis of pernicious anemia was 1.8 (CI, 0.8 to 3.3). The relative risk was greatest (4.1; CI, 1.7 to 8.7) in the 5-year period immediately after the diagnosis of pernicious anemia; during this period, 7 cases of colon cancers were observed but only 1.7 were expected (P less than 0.0001). CONCLUSION: Although the overall risk does not achieve statistical significance, patients with pernicious anemia may have an increased risk for colorectal adenocarcinoma in the 5 years after diagnosis.

Adenocarcinoma↗

Post-transcriptional regulation of 5S rRNA synthesis following myoblast differentiation.

Terminal differentiation of proliferating rat L6 myoblasts to syncytial multi-nucleated myotubes results in a decline in the cellular levels of 5S rRNA. This decrease parallels the drop in ribosome number and the reduction in 45S rRNA precursor gene transcription previously documented [Jacobs et al. (1985) Eur. J. Biochem. 150, 255]. The activity of RNA polymerase III in 100,000 x g supernatants from myoblasts and myotubes is similar suggesting the level of this enzyme does not limit 5S rRNA synthesis. Nuclear and cell-free transcription assays were used to measure 5S rRNA synthesis in myoblasts and myotubes. No differences were observed in the rate of 5S rRNA gene transcription, thus demonstrating that 5S rRNA levels in myotubes are not transcriptionally controlled. To determine whether RNA stability plays a role, the half-life of newly synthesized 5S rRNA was measured in vivo. The half-life of nuclear 5S rRNA was calculated to be 370 min and 65 min in myoblasts and myotubes, respectively, demonstrating that the decrease in 5S rRNA levels following terminal differentiation is regulated post-transcriptionally.

Animals↗

RNA polymerase II-directed gene transcription by rat skeletal muscle nuclear extracts.

A cell-free transcription system was developed using nuclear extracts of rat skeletal muscle to examine the transcription of specific genes involved in ribosome biogenesis and histone synthesis. Isolation and purification of muscle tissue nuclei were required prior to obtaining a transcriptionally active extract. The transcriptional abilities of myoblast, myotube, and muscle tissue nuclear extracts were then compared using the adenovirus major late promoter as a reporter gene. Transcription of r-protein L32 and histone H4 gene templates remained high in all extracts while histone H3 gene transcription was reduced in both myotube and muscle tissue extracts. These data indicate that transcription of these genes in myotubes and muscle tissue nuclear extracts is similar. Therefore, the L6 myoblast system accurately reflects the ability of intact muscle tissue to transcribe the genes concerned with histone production and ribosome biogenesis.

Animals↗

Tetanus: an uncommon cause of dysphagia.

A 53-year-old woman was examined at our medical center because of progressive dysphagia of 14 days' duration and a severe inability to open her mouth and swallow saliva. A barium esophagogram showed no obstruction, but pooling of barium in the hypopharynx suggested a neuromuscular disorder. The clinical diagnosis of tetanus was confirmed by electromyography. With appropriate therapy, the patient recovered during a period of 6 weeks. This case illustrates both an uncommon cause of dysphagia and an uncommon initial manifestation of tetanus.

Age Factors↗

The function of proteins that interact with mRNA.

Specific proteins are associated with mRNA in the cytoplasm of eukaryotic cells. The complement of associated proteins depends upon whether the mRNA is an integral component of the polysomal complex being translated, or, alternatively, whether it is part of the non-translated free mRNP fraction. By subjecting cells to ultraviolet irradiation in vivo to cross-link proteins to mRNA, mRNP proteins have been shown to be associated with specific regions of the mRNA molecule. Examination of mRNP complexes containing a unique mRNA has suggested that not all mRNA contain the same family of associated RNA binding proteins. The functions of mRNA associated proteins may include a role in providing stability for mRNA, and/or in modulating translation. With the recent demonstrations that both free and polysomal mRNPs are associated with the cytoskeletal framework, specific mRNP proteins may play a role in determining the subcellular localization of specific mRNPs.

Animals↗

Cytoskeletal association of muscle-specific mRNAs in differentiating L6 rat myoblasts.

The importance of the cytoskeleton in protein synthesis was studied in differentiating L6 rat myoblasts. Soluble and cytoskeletal fractions obtained after gentle, non-ionic detergent lysis of myoblasts and myotubes were analysed for the presence of ribosomes and mRNPs. Polysomal mRNPs were predominantly associated with the cytoskeletal framework and free mRNPs were present in both soluble and cytoskeletal fractions. An examination of the distribution of specific mRNAs in the polysomal and free mRNP populations of both cytoplasmic fractions revealed differences in the pattern of their distribution. It is further demonstrated that in the L6 rat myoblast system, ribosomes and mRNA (or mRNP) are not associated with the microfilaments, unlike in other systems studied.

Actin Cytoskeleton↗

Antibiotic prophylaxis for percutaneous endoscopic gastrostomy. A prospective, randomized, double-blind clinical trial.

Study Objective. To determine if prophylactic use of cefazolin reduces peristomal wound infection associated with percutaneous endoscopic gastrostomy. Design. Prospective, randomized, double-blind, placebo-controlled clinical trial. Setting. Academic medical center, referral-based, gastroenterology service. Patients. One hundred thirty hospitalized patients, 23 of whom were excluded. Of the remaining 107 patients, 52 (group I) were already using antibiotics at the time of randomization for gastrostomy, whereas 55 (group II) were not. Interventions. Patients received either intravenous saline as a placebo or intravenous cefazolin (1 g) 30 minutes before gastrostomy. Measurements and Main Results. For 1 week after gastrostomy, the peristomal area was evaluated and a score assigned each day for erythema (0 to 4), induration (0 to 3), and exudate (0 to 4). A maximum combined score of 8 or more or the development of pus was a criterion for infection. None of the patients in group I developed a wound infection. Only 2 of 27 group II patients given prophylaxis developed a wound infection, compared with 9 of 28 patients not given prophylaxis, a difference of 25% (95% confidence interval, 4.8 to 44.6%; p less than 0.025). The number of patients who developed a wound infection was 0 of 52 in group I and 2 of 27 in group II patients who received cefazolin, a difference of 7.4% (95% confidence interval, -2.5 to 17.3%; p = 0.07). Conclusion. Cefazolin prophylaxis significantly reduces the risk for peristomal wound infection associated with percutaneous endoscopic gastrostomy. It is needed, however, only for patients not already receiving antibiotic treatment at the time of gastrostomy.

Aged↗

Percutaneous endoscopic gastrostomy. Indications, success, complications, and mortality in 314 consecutive patients.

The aim of this study was to determine the indications, success rate, procedure-related mortality, and major and minor complication rates in 314 consecutive patients in whom we attempted a percutaneous endoscopic gastrostomy. The most common indications for placement of the gastrostomy tube were neurologic (n = 235, 75%) and oropharyngeal disorders (n = 42, 13%). We noted that the gastrostomy tube was successfully placed in 299 (95%) of the 314 patients. Ninety-three percent (n = 291) of the patients had the procedure performed in the hospital and 7% (n = 23) were outpatients when the procedure was performed. In those patients with stable underlying conditions, the procedure can safely be performed in the outpatient setting. A low rate of procedure-related mortality (1%), major complication (3%), and minor complication (13%) was noted. Our experience suggests that the percutaneous endoscopic gastrostomy is safe and has a low mortality rate even in patients who are medically debilitated secondary to their underlying disease.

Adolescent↗

The structure and function of the outpatient endoscopy unit.

The authors present an analysis of the requirements for space, equipment, and personnel for an outpatient unit. These studies were derived from personnel and procedure time studies, evaluation of equipment and maintenance costs, and utilization of space studies and should be applicable to any outpatient endoscopy unit performing more than 1000 procedures per year.

Ambulatory Care↗

Use of gastroscopy in a community: a population-based study in Olmsted County, Minnesota.

We determined the use of gastroscopy in a defined population (Olmsted County, Minnesota) during the 3-year period 1978 through 1980. In slightly more than 271,000 person-years of observation, 418 residents underwent gastroscopy on 487 separate occasions. When age- and sex-adjusted to the structure of the US white population in 1980, the utilization rate was 215.9 per 100,000 person-years. With extrapolation of these data, approximately 500,000 gastroscopies would be expected to be performed in the United States each year.

Adult↗

Influence of hepatic reserve and cause of esophageal varices on survival and rebleeding before and after the introduction of sclerotherapy: a retrospective analysis.

Esophageal variceal sclerotherapy has been enthusiastically accepted as the procedure of choice for patients with variceal hemorrhage. Because the relationships among liver function, different causes of varices, survival, and rebleeding rates have not been well established in sclerotherapy trials, this enthusiasm may be unjustified. We studied these relationships in 80 patients with bleeding esophageal varices who were admitted to hospitals affiliated with our clinic between 1978 and 1980 and who did not receive sclerotherapy and in 162 patients admitted between 1980 and 1982 who received sclerotherapy with ethanolamine oleate. In both groups of patients, survival and bleeding-free intervals were significantly related (P less than 0.005 and P less than 0.01, respectively) to hepatic reserve (Child's class). In addition, patients with nonalcohol-related liver disease and poor hepatic reserve (Child's class C) had reduced survival and bleeding-free intervals compared with patients in class C with alcohol-related liver disease. Similar probabilities of survival and bleeding-free intervals were noted for Child's class subgroups and etiologic subgroups in the sclerotherapy and nonsclerotherapy groups, although a formal comparison was not made because of the retrospective nature of this study. Indications that sclerotherapy increases survival and reduces rebleeding may be due to different distributions of Child's classes and causes of varices within sclerotherapy and nonsclerotherapy groups in published control trials.

Esophageal and Gastric Varices↗

Risk of development of gastric carcinoma in patients with pernicious anemia: a population-based study in Rochester, Minnesota.

To determine the long-term risk of the development of gastric cancer among patients with pernicious anemia, we identified the 152 residents of Rochester, Minnesota, who had well-documented pernicious anemia during the 30-year period 1950 through 1979. These patients were subsequently followed up for more than 1,550 person-years of observation. The observed risk of the development of a gastric cancer in this cohort was compared with that expected on the basis of incidence rates of gastric cancer for the local population. We found one case of gastric carcinoma among our 152 patients with pernicious anemia as compared with an expected incidence of 1.02 (relative risk, 1.0; 95% confidence interval, 0.02 through 5.5). We conclude that no strong indication exists for either radiographic or endoscopic surveillance in asymptomatic patients with pernicious anemia.

Adult↗

Systemic lupus erythematosus developing in patients with primary biliary cirrhosis.

Three patients with biopsy-proven primary biliary cirrhosis subsequently developed a multisystem disorder and serologic abnormalities consistent with systemic lupus erythematosus. In one patient, antimitochondrial antibody titers fell to undetectable levels after the development of the extrahepatic manifestations. No patient had been exposed to D-penicillamine or other drugs capable of inducing a lupus-like condition. These patients further emphasize the difficulties in disease classification and underline the systemic nature of chronic liver diseases such as primary biliary cirrhosis.

Adult↗

Aspirin-sulfinpyrazone in prophylaxis of deep venous thrombosis in total hip replacement.

In postoperative hip arthroplasty patients, treatment with aspirin and sulfinpyrazone resulted in a statistically significant reduction of venographically diagnosed thrombi in the proximal veins of the leg. This reduction was most apparent in thrombi that involved the iliac vein. When compared with their placebo-treated counterparts, female patients who received the active treatment experienced a statistically significant 75% reduction of thrombosis, compared with a 32% reduction for men that was not statistically significant. There were no serious adverse effects. Factors were identified that may influence the result of drug prophylaxis trials in deep-vein thrombosis.

Adult↗

The risk of gastric carcinoma after surgical treatment for benign ulcer disease. A population-based study in Olmsted County, Minnesota.

To determine the long-term risk of gastric cancer in benign peptic-ulcer disease, we studied 338 residents of Olmsted County, Minnesota, who had surgical treatment for benign peptic-ulcer disease in the 25-year period 1935-1959 and had no evidence of gastric cancer for five years after that surgery. These patients were subsequently followed for over 5635 person-years of observation. The risk of development of a gastric cancer in this group was compared with that expected on the basis of gastric-cancer incidence rates for the local population. Carcinomas in the gastric remnant developed in only two of these patients, as compared with an expected 2.6 primary gastric carcinomas (relative risk, 0.8 [95 per cent confidence interval, 0.1 to 2.7]). We conclude that there is no indication for endoscopic surveillance in asymptomatic patients with previous gastric surgery for benign peptic-ulcer disease.

Adult↗

Upper gastrointestinal hemorrhage.

Hemorrhage in the upper gastrointestinal tract can be a diagnostic and therapeutic challenge to the physician. Although some advances have been made in patient care, mortality from gastrointestinal bleeding has not decreased during the past 40 years. The initial priorities in the physical examination of the bleeding patient should be a rapid assessment of the hemodynamic status and evaluation of the circulatory state. Once the patient has been hemodynamically stabilized, endoscopy is the best available technique for identifying the bleeding lesion. Potential sources of the bleeding are duodenal ulcers, gastric ulcers, Mallory-Weiss tears, and esophageal varices. The classic indications for surgical intervention are loss of 30% of the estimated blood volume in the first 24 hours, a need for 1,500 ml of transfused blood per 24 hours to maintain stable hemodynamics, hemorrhage to the point of hypotension or shock, and rebleeding during medical therapy.

Endoscopy↗

Percutaneous endoscopic gastrostomy. Simplified access for enteral nutrition.

The recently described technique of endoscopic placement of a permanent feeding gastrostomy is reviewed with several modifications. Our experience in 23 adults has led us to conclude that this nonsurgical technique is the procedure of choice in achieving long-term enteral nutrition in patients who have an intact, nonobstructed gut and in whom the stomach can be directly apposed to the anterior abdominal wall.

Adolescent↗