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Biomedical subjects

B L Hanson

Publications and source records attributed to B L Hanson.

18 recordsLinked to original sources
PubMed2001

Methylation of histone H3 by coactivator-associated arginine methyltransferase 1.

The preferential in vitro methylation of histone H3 by coactivator-associated arginine methyltransferase 1 (CARM1) has been proposed as a basis for its ability to enhance gene transcription [Chen, D., et al. (1999) Science 284, 2174-2177]. To further evaluate the significance of H3 methylation, we studied the kinetics and site specificity of its modification by CARM1. Affinity-purified CARM1 methylated recombinant chick H3, which is free of posttranslational modifications, and calf thymus H3, which is heterogeneous with regard to preexisting modifications, equally well, exhibiting a V(max) of 4500 pmol min(-1) (mg of enzyme)(-1) and an apparent K(m) for H3 of < or = 0.2 microM. The catalytic efficiency (k(cat)/K(m)) of CARM1 toward H3 was at least 1000 times that toward R1 (GGFGGRGGFGG-amide), a highly effective substrate for protein arginine methyltransferase 1. Peptide mapping of 3H-methyl-labeled H3 indicated methylation at Arg-2, Arg-17, and Arg-26 in the N-terminal region and at one or more of four arginines (128/129/131/134) at the C-terminus. Two of the N-terminal sites, Arg-17 and Arg-26, occur in the sequence KAXRK and appear to be more efficiently methylated than Arg-2. CARM1 catalyzed formation of N(G),N(G)-dimethylarginine (asymmetric) but little or no N(G),N'(G)-dimethylarginine (symmetric) and no form of methyllysine. Amino acid analysis of untreated calf thymus H3 revealed that 3.7% of the molecules naturally contain asymmetric dimethylarginine and/or monomethylarginine. Our findings support the hypothesis that methylation of H3 may be involved in the mechanism of transcriptional coactivation by CARM1 of genes whose expression is under the control of nuclear receptors.

Amino Acid Sequence↗
PubMed2001

Endoscopic management of tumors of the major duodenal papilla: Refined techniques to improve outcome and avoid complications.

BACKGROUND: Adenomas of the major duodenal papilla have malignant potential and are traditionally treated by pancreaticoduodenectomy. This is a report of our experience with endoscopic management and a description of techniques for decreasing complications and enhancing efficacy. METHODS: Forty-one patients were referred for endoscopic management of papillary tumors. If there was no duct invasion and the appearance suggested a benign lesion, biductal sphincterotomy with pancreatic duct stent placement was performed. If the lesion could be elevated by injection of an epinephrine solution, piecemeal resection was performed. The base of the lesion was thermally ablated as needed. Resection/ablation together with stent removal was performed 1 month later. RESULTS: Nine patients (22%) had lesions other than papillary adenoma or cancer. Malignant appearance, ductal stricturing, or extension into the ducts was found in 16 of 41 patients (39%) in whom biopsy specimens alone were obtained. Three patients with adenomas (7%) did not undergo endoscopic resection (because of extremely large lesions and/or comorbid illnesses). Thirteen patients with adenomas (32%) had endoscopic resection; 12 (92%) were lesion-free after 32 ERCPs (mean 2.7). Endoscopic management was unsuccessful in 1 patient (8%). Pancreatitis developed in 1 patient. CONCLUSIONS: Endoscopically treatable papillary neoplasms can be identified on the basis of endoscopic, radiographic, and biopsy features. Preresection sphincterotomy, stent placement, elevation by epinephrine injection, and piecemeal resection may reduce complications and permit more aggressive treatment.

Adenoma↗
PubMed2000

Asymmetries in the nucleosome core particle at 2.5 A resolution.

The 2.5 A X-ray crystal structure of the nucleosome core particle presented here provides significant additions to the understanding of the nucleosome, the fundamental unit of chromatin structure. Extensions are made to the structure of the N-terminal histone tails and details are provided on hydration and ion binding. The structure is composed of twofold symmetric molecules, native chicken histone octamer cores and the DNA palindrome, which were expected to form a perfectly twofold symmetric nucleosome core particle. In fact, the result is asymmetric owing to the binding of the DNA to the protein surface and to the packing of the particles in the crystal lattice. An analysis is made of the asymmetries by comparisons both within the nucleosome core particle and to the structure of the histone octamer core of the nucleosome.

Amino Acid Sequence↗
PubMed2000

Infected pancreatic pseudocysts with colonic fistula formation successfully managed by endoscopic drainage alone: report of two cases.

Fistulization of pancreatic pseudocysts into surrounding viscera is a well-known phenomenon and usually requires surgical management. We report two cases of pancreatic pseudocysts that developed spontaneous fistulas to the colon with resulting fever and abdominal pain. The patients were managed nonoperatively with a combination of endoscopic drainage and antibiotics, and their pseudocysts and fistulas resolved. The patients have remained symptom-free for a mean of 14 months of follow-up.

Abdominal Abscess↗
PubMed1999

Endoscopic treatment of pancreatic duct stones using a 10F pancreatoscope and electrohydraulic lithotripsy.

BACKGROUND: Endoscopic therapy with adjunctive extracorporeal shock wave lithotripsy fails to provide clearance of pancreatic duct stones in up to 25% of symptomatic patients. Direct contact lithotripsy may provide an additional option for removal of refractory stones. We report our initial experience using a prototype 10F "baby" endoscope to administer electrohydraulic lithotripsy. METHODS: Five patients failing extracorporeal shock wave lithotripsy and one patient with recurrent pancreatic duct stones after surgery were selected to undergo endoscopic electrohydraulic lithotripsy. After pancreatic sphincterotomy and balloon dilation (8 or 10 mm), the 10F endoscope was introduced and electrohydraulic lithotripsy was used to fragment stones under direct visualization. RESULTS: Six patients underwent 9 intraductal electrohydraulic lithotripsy procedures. Complete or partial pancreatic duct clearance was accomplished in all but one. No complications from the lithotripsy procedure were noted. The 5 patients with partial or complete duct clearance experienced complete relief of abdominal pain of at least 6 months' duration following their final procedure. CONCLUSION: Electrohydraulic lithotripsy within the pancreatic duct provides an adjunctive endoscopic option for treatment of patients with symptomatic pancreatic duct stones. Our initial experience suggests that electrohydraulic lithotripsy therapy can successfully fragment stones refractory to conventional endoscopic stone extraction methods or extracorporeal shock wave lithotripsy. Further experience is necessary to establish the risks of electrohydraulic lithotripsy within the pancreatic duct.

Aged↗
PubMed1999

Macromolecular crystal annealing: evaluation of techniques and variables.

Additional examples of successful application of macromolecular crystal annealing are presented. A qualitative evaluation of variables related to the annealing process was conducted using a variety of macromolecular crystals to determine in which cases parameters may be varied and in which cases the original macromolecular crystal annealing protocol is preferred. A hypothesis is presented relating the solvent content of the crystal to the specific protocol necessary for the successful application of annealing.

Animals↗
PubMed1998

Dilated common channel syndrome: endoscopic diagnosis, treatment, and relationship to choledochocele formation.

BACKGROUND: Choledochoceles (type III biliary cysts) are cystic dilations of the terminal common bile duct or common pancreatobiliary channel. Although no size criteria have been defined, it is generally assumed these must be large. However, we describe patients who do not meet the perceived size criteria for choledochoceles, but who nonetheless have a dilated common pancreatobiliary channel. METHODS: We reviewed the presenting symptoms, endoscopic and radiographic findings, and response to endoscopic therapy of patients meeting our criteria for the dilated common channel syndrome. RESULTS: Of 2847 patients undergoing ERCP, 100 (3.5%) had the dilated common channel syndrome. Common presenting symptoms and signs included abdominal pain in 97%, abnormal liver function test(s) in 66%, and a history of acute or recurrent pancreatitis in 46%. A bulge was visible above the papilla in 88%, with a dilated common bile duct in 54% and a dilated pancreatic duct in 28%. After endoscopic unroofing of the common channel, 77% had complete and long-lasting resolution of symptoms, 18% had partial or transient improvement, and 5% had no change. CONCLUSIONS: Although classic choledochoceles are rare, a lesser degree of dilation of the common channel is more frequent than generally appreciated. We postulate that this finding represents an "incomplete," acquired form of choledochocele, possibly caused by underlying papillary stenosis. Whatever the etiology and appropriate term, the presence of a dilated common channel predicts a high rate of clinical response to endoscopic therapy.

Adult↗
PubMed1998

Endoscopic pancreatic sphincterotomy: indications, outcome, and a safe stentless technique.

BACKGROUND: Endoscopic pancreatic sphincterotomy is less widely practiced than biliary sphincterotomy, in part because of the lack of firm data regarding its indications and safety. In addition, recent reports of ductal and parenchymal changes occurring after pancreatic stenting raise concerns about the standard practice of stent placement at the time of pancreatic sphincterotomy. We report our experience with pancreatic sphincterotomy and describe the use of a technique involving overnight nasopancreatic drainage rather than stenting. METHODS: We reviewed the records of the 164 pancreatic sphincterotomies performed on 160 patients at our institution between January 1, 1991, and October 1, 1996, comparing procedures done with overnight nasopancreatic catheter placement with those done with stenting or no drainage. We also examined the long-term clinical outcome of patients after pancreatic sphincterotomy. RESULTS: Of the 164 sphincterotomies, 98 were done with overnight nasopancreatic drainage, 50 with stent placement, and 16 with no drainage. Complications (all pancreatitis) were significantly more frequent in the group with no drainage (12.5%) as compared with those with drainage (0.7%); p < 0.003. Nasopancreatic drainage was as safe as stent placement, with no complications after 98 procedures. Pancreatic sphincterotomy was effective when used as primary therapy, with 64% of patients so treated experiencing complete and long-lasting resolution of symptoms after the procedure. CONCLUSIONS: Pancreatic sphincterotomy is safe and effective, although pancreatic drainage is required to reduce the incidence of pancreatitis. Overnight nasopancreatic drainage is the method of choice, as it carries as low a complication rate as stent placement, but without the need for a repeat procedure, and presumably without the risk of ductal and parenchymal damage.

Case-Control Studies↗
PubMed1998

Endoscopic sphincterotomy for stones by experts is safe, even in younger patients with normal ducts.

OBJECTIVE: To provide current information on the risks of endoscopic sphincterotomy for stone. SUMMARY BACKGROUND DATA: In recent years (since the popularity of laparoscopic cholecystectomy), endoscopic sphincterotomy has been used increasingly for the management of bile duct stones in relatively young and healthy patients. The validity of this trend has been questioned using data on short-term complications derived from earlier decades that involved more elderly and high-risk patients. METHODS: Seven academic centers collected data prospectively using a common database. Complications within 30 days of the procedures were documented by standard criteria. RESULTS: Of 1921 patients, 112 (5.8%) developed complications; two thirds of these events were graded as mild (<3 days in hospital). There was no evidence of increased risk in younger patients or in those with smaller bile ducts. There was only one severe complication and there were no fatalities in 238 patients age <60, with bile duct diameters of <9 mm. CONCLUSION: Sphincterotomy for stones can be performed very safely by experienced endoscopists.

Age Factors↗
PubMed1995

Combined modality treatment of symptomatic pancreatic ductal lithiasis.

OBJECTIVE: To assess the efficacy and safety of the removal of pancreatic duct stones by a combined modality approach in patients with pancreatic ductal lithiasis and recurrent abdominal pain. DESIGN: Retrospective review with a mean follow-up of 19 months (range, 1 to 56 months). SETTING: A tertiary care, private community hospital with a university affiliation. PATIENTS: The records of patients who presented to the hospital or who were referred with recurrent abdominal pain and who were demonstrated to have pancreatic ductal lithiasis between 1989 and 1994 were reviewed. Patients were assessed by their clinical response to pancreatic duct stone extraction by a variety of therapeutic interventions. RESULTS: Fifteen patients were included in the study. One patient was excluded from analysis because of a concurrent choledochocele. Two patients required operative decompression and stone extraction for endoscopically inaccessible stones. Six patients were treated with endoscopic management alone, and six were treated with a combination of extracorporeal shock wave lithotripsy and endoscopic stone retrieval. Twelve patients had complete clearance of the pancreatic duct. One patient had a stone that was not removed, but adequate pancreatic ductal decompression was achieved. The remaining patient had incomplete clearance of pancreatic stone fragments following extracorporeal shock wave lithotripsy but had adequate ductal drainage. No patient has required further therapy or hospitalization for abdominal pain. No complications occurred as a result of any intervention in this study. CONCLUSIONS: A multidisciplinary combined modality approach is a safe and effective method for extracting pancreatic duct stones in symptomatic patients. Stone extraction and reestablishment of adequate ductal drainage appear to relieve symptoms in some patients.

Abdominal Pain↗
PubMed1993

Principles and pitfalls in designing site-directed peptide ligands.

An immunoglobulin light chain dimer with a large generic binding cavity was used as a host molecule for designing a series of peptide guest ligands. In a screening procedure peptides coupled to solid supports were systematically tested for binding activity by enzyme linked immunosorbent assays (ELISA). Key members of the binding series were synthesized in milligram quantities and diffused into crystals of the host molecule for X-ray analyses. These peptides were incrementally increased in size and affinity until they nearly filled the cavity. Progressive changes in binding patterns were mapped by comparisons of crystallographically refined structures of 14 peptide-protein complexes at 2.7 A resolution. These comparisons led to guidelines for ligand design and also suggested ways to modify previously established binding patterns. By manipulating equilibria involving histidine, for example, it was possible to abolish one important intramolecular interaction of the bound ligand and substitute another. These events triggered a change in conformation of the ligand from a compact to an extended form and a comprehensive change in the mode of binding to the protein. In dipeptides of histidine and proline, protonation of both imidazolium nitrogen atoms was used to program an end-to-end reversal of the direction in which the ligand was inserted into the binding cavity. Peptides cocrystallized with proteins produced complexes somewhat different in structure from those in which ligands were diffused into preexisting crystals. In such a large and malleable cavity, space utilization was thus different when a ligand was introduced before the imposition of crystal packing restraints.

Bence Jones Protein↗
PubMed1993

Utility of endoscopic retrograde cholangiopancreatography in the evaluation of idiopathic abdominal pain.

We investigated the role of endoscopic retrograde cholangiopancreatography in 86 consecutive patients with idiopathic chronic or recurrent abdominal pain. There were 18 males and 68 females with a mean age of 48 yr. Forty patients (47%) had previous cholecystectomy. Patients were divided into two groups: group I (normal serum alkaline phosphatase and total bilirubin) (n = 52), and group II (elevated serum alkaline phosphatase and/or total bilirubin) (n = 34). Pancreatograms were normal in all patients, including five with pancreas divisum. Cholangiograms were abnormal in 10 of the 34 patients in group II (30%), and in only three of the 52 patients in group I (6%) (p = 0.003). Bile duct stones were present in 18% of the patients in group II, and in none of the patients in group I (p = 0.003). Of the 40 post-cholecystectomy patients, four patients had bile duct stones and five had common bile duct dilation without stones. However, no stones were found in any post-cholecystectomy patients with normal liver tests. Of the 46 patients with gallbladder in situ, two patients with abnormal liver tests had common bile duct stones and two patients had common bile duct dilation without stones. These results indicate that, among patients with idiopathic abdominal pain, cholangiography should be performed primarily in those with abnormal liver tests; however, further investigation with pancreatography is unnecessary.

Abdominal Pain↗
PubMed1980

Bicultural training for new graduates.

This article demonstrates the success of a bicultural training program in helping new graduates successfully integrate the transition from student to staff nurse. It describes how to implement this program and how to train 'trainers' for it. Results based on turnover rates and cost-effectiveness verify its usefulness.

Adaptation, Psychological↗