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Biomedical subjects

J D Lewis

Publications and source records attributed to J D Lewis.

At least 55 records · Page 3Linked to original sources

Cysteine-containing histone H1-like (PL-I) proteins of sperm.

We have determined the presence of cysteine in the protein PL-I from the sperm of the surf clam Spisula solidissima. The existence of cysteine in this histone H1-related protein is responsible for its previously described aggregation behavior. The location of this residue, within the trypsin-resistant domain of the protein, has been established. We have also shown that cysteine is ubiquitously present in the PL-I proteins from the sperm of other bivalve mollusks but is absent from other PL of smaller molecular mass (PL-II, PL-III, PL-IV). We have also found cysteine to be present in the PL-I from a tunicate (Chelysoma productum) but absent in a PL-I from a fish (Mullus barbatus). The possible significance of the unusual occurrence of cysteine in these histone-H1-related proteins is discussed.

Amino Acid Sequence↗

Cancer risk in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at increased risk for developing cancer of the gastrointestinal tract, particularly colorectal cancer. Because of the relative rarity of IBD in the general population, it has been difficult to quantify this risk. Efforts to reduce the risk have included both prophylactic surgery and endoscopic screening programs. Because of the potential impact on quality of life and life expectancy, the optimal strategy for reducing this risk has not been defined. This article reviews the current literature relating to the risk of cancer for patients with IBD and methods to reduce this risk.

Adenocarcinoma↗

Primary care physicians' decisions to perform flexible sigmoidoscopy.

OBJECTIVE: This study was designed to identify factors that influence primary care physicians' willingness to perform flexible sigmoidoscopy. MEASUREMENTS: Using a mailed questionnaire, we surveyed all 161 primary care physicians participating in a large health care system. We obtained information on training, current practice patterns, beliefs about screening for colorectal cancer, and the influence of various factors on their decision whether or not to perform flexible sigmoidoscopy in practice. MAIN RESULTS: Of the 131 physicians included in the analysis, 68 (52%) reported training in flexible sigmoidoscopy, of whom 36 (53%) were currently performing flexible sigmoidoscopy in practice. Time required to perform flexible sigmoidoscopy, availability of adequately trained staff, and availability of flexible sigmoidoscopy services provided by other clinicians were identified most often as reasons not to perform the procedure in practice. Male physicians were more likely than female physicians to report either performing flexible sigmoidoscopy or desiring to train to perform flexible sigmoidoscopy (odds ratio 2.61; 95% confidence interval 1.10, 6.23). This observed difference appears to be mediated through different weighting of decision criteria by male and female physicians. CONCLUSIONS: Approximately half of these primary care physicians trained in flexible sigmoidoscopy chose not to perform this procedure in practice. Self-perceived inefficiency in performing office-based flexible sigmoidoscopy deterred many of these physicians from providing this service for their patients.

Adult↗

Screening for colorectal cancer and other GI cancers.

Most of the major advances in the screening for gastrointestinal cancers this year were in the area of colorectal cancer screening. Currently, screening is recommended for the prevention of colorectal cancer in average and high-risk populations. For average risk populations, large randomized trials support the use of screening fecal occult blood testing, and case-control studies support the use of screening sigmoidoscopy. This year, several investigators have addressed issues related to the probability of identifying advanced lesions in the proximal colon following a positive screening flexible sigmoidoscopy. Similarly, two studies identified that villous histology in an index polyp was associated with an increased risk of recurrent colonic polyps. Additionally, two large trials provided new insight about the prevalence of mutations in the MLH1 or MSH2 mismatch-repair genes among patients with colorectal cancer. Lastly, a case-control study from Sweden provided the best evidence to date that surveillance colonoscopies for patients with long-standing ulcerative colitis may reduce cancer-related mortality. Although further work is needed, these studies have served to advance our knowledge of colorectal cancer screening substantially.

Colorectal Neoplasms↗

Colorectal cancer screening with sigmoidoscopy: primary care issues.

Colorectal cancer is the second leading cause of death from cancer in the U.S., behind lung cancer. Numerous medical societies recommend routine screening for colorectal cancer with flexible sigmoidoscopy for people 50 and over. But who will perform the procedure, and who will pay for it? The case of flexible sigmoidoscopy illustrates the economic and practical issues of introducing a screening procedure into primary care practice. This Issue Brief investigates the role of primary care physicians in providing this service as part of routine care, and identifies attitudinal and financial barriers to overcome.

Adult↗

Splenic vein thrombosis secondary to focal pancreatitis diagnosed by endoscopic ultrasonography.

We report splenic vein thrombosis diagnosed by endoscopic ultrasonography (EUS) after the failure of extracorporeal ultrasound and contrast enhanced computed tomography to establish the diagnosis in a patient with gastrointestinal bleeding and anemia. Subsequent preoperative magnetic resonance imaging revealed findings of retroperitoneal fibrosis and confirmed the EUS findings. Splenic vein thrombosis is a well-known cause of gastrointestinal bleeding and splenomegaly; pancreatitis and pancreatic tumors are its most common underlying causes. Abdominal ultrasound and computed tomography are frequently used to diagnose splenic vein thrombosis. We discuss the use of EUS for diagnosis of vascular anomalies in the gastrointestinal tract and the association of splenic vein thrombosis, retroperitoneal fibrosis, and pancreatitis.

Endosonography↗

Hodgkin's disease diagnosed by endoscopic ultrasound-guided fine needle aspiration of a periduodenal lymph node.

Hodgkin's disease rarely presents as obstructive jaundice. We report a case of Hodgkin's disease arising in periduodenallymph nodes, presenting with biliary obstruction, definitively diagnosed on cytologic material obtained by endosonographically-guided real-time fine needle aspiration biopsy and confirmed at laparotomy. The medical literature pertaining to the use of endosonography and fine needle aspiration biopsy for pancreatic lesions and abdominal lymphoma is reviewed. Currently available data support the use of fine needle aspiration biopsy in establishing the diagnosis of lymphoma. This case highlights the utility of endoscopic ultrasonography with endosonographically guided real-time fine needle aspiration biopsy in diagnosing and managing patients with extrahepatic biliary obstruction or suspected abdominal lymphoma. Pairing endosonographically guided real-time fine needle aspiration biopsy with on-site cytologic assessment and immediate specimen triage can lead to definitive diagnosis of abdominal lymphoma, avoiding surgical intervention in many cases.

Adult↗

The role of the cap structure in RNA processing and nuclear export.

The cap structure that is characteristic of all polymerase-II-transcribed RNAs has been shown to play an important role in many aspects of RNA metabolism including RNA processing, RNA nuclear transport, and translation initiation. The effects of the cap structure on these different processes is mediated by proteins that recognise and bind to it, and are therefore generically called cap-binding proteins. For example, the cap-binding protein eIF4E, in a complex with other proteins, mediates the effect of the cap on the initiation of translation. EIF-4E is predominantly localised in the cytoplasm. In the last five years, it has been demonstrated that a second cap-binding protein complex, which is mainly localised in the nucleus, mediates the stimulatory effects of the cap in nuclear processes such as pre-mRNA splicing, RNA 3'-end formation, and RNA nuclear export. The purpose of this review is to summarise our current knowledge on the role of the cap structure and of the cap-binding protein complex in nuclear RNA metabolism and present evidence that at least some processes may be coupled in vivo.

Animals↗

Urease-based tests for Helicobacter pylori gastritis. Accurate for diagnosis but poor correlation with disease severity.

To determine whether the urease-based CLOtest or low-dose 14C urea breath test can predict severity of gastritis or the presence of peptic ulcers, we studied 84 patients presenting for upper endoscopy. Antral biopsies were obtained for histologic analysis and CLOtesting, and urea breath testing was performed. The time to a positive CLOtest and the breath test peak values were correlated with endoscopic findings, severity of gastritis, and bacterial burden. Twenty-four patients had positive urea breath test results (22 with positive CLOtests). Patients with positive breath test results were more likely to have duodenal ulcers, higher grades of gastritis, and increased bacterial burden (p < 0.01 for all comparisons). Correlation between the time to a positive CLOtest or peak breath test values and gastritis severity or bacterial burden was poor (p > 0.05 for all comparisons). In patients with positive tests, no difference was observed between the time to a positive CLOtest or peak breath test value in patients with or without peptic ulcers (p < 0.2 for all comparisons). The low-dose 14C urea breath test and the CLOtest are both accurate for Helicobacter pylori diagnosis. However, neither test predicts the severity of the gastritis, the degree of bacterial burden, or the presence of peptic ulcers.

Adult↗

A yeast cap binding protein complex (yCBC) acts at an early step in pre-mRNA splicing.

The function in splicing of a heterodimeric nuclear cap binding complex (yCBC) from the yeast Saccharomyces cerevisiae has been examined. Immunodepletion of splicing extracts with antibodies directed against one component of the complex, yCBP80, results in the efficient co-depletion of the second component, yCBP20, producing CBC-deficient splicing extract. This extract exhibits strongly reduced splicing efficiency and similar reductions in the assembly of both spliceosomes and of the earliest defined precursors to spliceosomes, commitment complexes. The addition of highly purified yCBC substantially restores these defects. These results, together with other data, suggest that CBCs play a highly conserved role in the recognition of pre-mRNA substrates at an early step in the splicing process.

Amino Acid Sequence↗

A nuclear cap-binding complex facilitates association of U1 snRNP with the cap-proximal 5' splice site.

The mechanism by which intron-containing RNAs are recognized by the splicing machinery is only partly understood. A nuclear cap-binding complex (CBC), which specifically recognizes the monomethyl guanosine cap structure carried by RNA polymerase II transcripts, has previously been shown to play a role in pre-mRNA splicing. Using a combination of splicing complex and psoralen cross-linking analysis we demonstrate that CBC is required for efficient recognition of the 5' splice site by U1 snRNP during formation of E (early) complex on a pre-mRNA containing a single intron. However, in a pre-mRNA containing two introns, CBC is not required for splicing of the cap distal intron. In this case, the presence of an intact polypyrimidine tract in the cap-proximal intron renders splicing of the cap-distal intron independent of CBC. These results support models in which the splice sites in a pre-mRNA are originally recognized by interactions spanning exons. The defects in splicing and U1 snRNP binding caused by CBC depletion can be specifically reversed by recombinant CBC. In summary, efficient recognition of the cap-proximal 5' splice site by U1 snRNP is facilitated by CBC in what may be one of the earliest steps in pre-mRNA recognition. Data in Colot et al. (this issue) indicate that this function of CBC is conserved in humans and yeast.

Base Sequence↗

Scores on self-actualization for gifted junior high school students.

Self-actualization scores of 47 gifted students in Grades 7 and 8 were assessed using the Reflections of Self by Youth (ROSY), the Maslowian Scale, and the Personal Orientation Inventory. No gender differences were observed. Students in Grade 7 scored significantly higher on the ROSY; students in Grade 8 scored significantly higher on the Maslowian Scale Psychological subscale and Total score. Scores on the Maslowian Scale Fundamentals and Self-actualization subscales and Personal Orientation Inventory were not different for any group. Correlations among the three measures of self-actualization are presented.

Adolescent↗

A computer-controlled conformal radiotherapy system. II: Sequence processor.

PURPOSE: A sequence processor (SP) is described as part of a larger computer-controlled conformal radiotherapy system (CCRS). The SP provides the means to accept and then translate highly sophisticated radiation therapy treatment plans into vendor specific instructions to control treatment delivery on a computer-controlled treatment machine. METHODS AND MATERIALS: The sequence processor (SP) is a small workstation computer that interfaces to the control computer of computer-controlled treatment machines, and to other parts of the larger CCRS system. The system reported here has been interfaced to a computer-controlled racetrack microtron with two treatment gantries, and also to other linear accelerator treatment machines equipped with multileaf collimators. An extensive design process has been used in defining the role of the SP within the context of the larger CCRS project. Flexibility and integration with various components of the project, including databases, treatment planning system, graphical simulator, were key factors in the development. In conjunction with the planned set of treatment fields, a procedural scripting language is used to define the sequence of treatment events that are performed, including operator interactions, communications to other systems such as dosimetry and portal imaging devices, and database management. RESULTS: A flexible system has been developed to allow investigation into procedural steps required for simulating and delivering complex radiation treatments. The system has been used to automate portions of the acceptance testing for the control system of the microtron, and is used for routine daily quality assurance testing. The sequence processor system described here has been used to deliver all clinical treatments performed on the microtron system in 2 years of clinical treatment (more than 200 patients treated to a variety of treatment sites). CONCLUSIONS: The sequence processor system has enabled the delivery of complex treatment using computer-controlled treatment machines. The flexibility of the system allows integration with secondary devices and modification of procedural steps, making it possible to develop effective techniques for insuring safe and efficient computer-controlled conformal radiation therapy treatments.

Computer Simulation↗

A computer-controlled conformal radiotherapy system. I: Overview.

PURPOSE: Equipment developed for use with computer-controlled conformal radiotherapy (CCRT) treatment techniques, including multileaf collimators and/or computer-control systems for treatment machines, are now available. The purpose of this work is to develop a system that will allow the safe, efficient, and accurate delivery of CCRT treatments as routine clinical treatments, and permit modifications of the system so that the delivery process can be optimized. METHODS AND MATERIALS: The needs and requirements for a system that can fully support modern computer-controlled treatment machines equipped with multileaf collimators and segmental or dynamic conformal therapy capabilities have been analyzed and evaluated. This analysis has been used to design and then implement a complete approach to the delivery of CCRT treatments. RESULTS: The computer-controlled conformal radiotherapy system (CCRS) described here consists of a process for the delivery of CCRT treatments, and a complex software system that implements the treatment process. The CCRS system described here includes systems for plan transfer, treatment delivery planning, sequencing of the actual treatment delivery process, graphical simulation and verification tools, as well as an electronic chart that is an integral part of the system. The CCRS system has been implemented for use with a number of different treatment machines. The system has been used clinically for more than 2 years to perform CCRT treatments for more than 200 patients. CONCLUSIONS: A comprehensive system for the implementation and delivery of computer-controlled conformal radiation therapy (CCRT) plans has been designed and implemented for routine clinical use with multisegment, computer-controlled, multileaf-collimated conformal therapy. The CCRS system has been successfully implemented to perform these complex treatments, and is considered quite important to the clinical use of modern computer-controlled treatment techniques.

Equipment Design↗

A computer-controlled conformal radiotherapy system. IV: Electronic chart.

PURPOSE: The design and implementation of a system for electronically tracking relevant plan, prescription, and treatment data for computer-controlled conformal radiation therapy is described. METHODS AND MATERIALS: The electronic charting system is implemented on a computer cluster coupled by high-speed networks to computer-controlled therapy machines. A methodical approach to the specification and design of an integrated solution has been used in developing the system. The electronic chart system is designed to allow identification and access of patient-specific data including treatment-planning data, treatment prescription information, and charting of doses. An in-house developed database system is used to provide an integrated approach to the database requirements of the design. A hierarchy of databases is used for both centralization and distribution of the treatment data for specific treatment machines. RESULTS: The basic electronic database system has been implemented and has been in use since July 1993. The system has been used to download and manage treatment data on all patients treated on our first fully computer-controlled treatment machine. To date, electronic dose charting functions have not been fully implemented clinically, requiring the continued use of paper charting for dose tracking. CONCLUSIONS: The routine clinical application of complex computer-controlled conformal treatment procedures requires the management of large quantities of information for describing and tracking treatments. An integrated and comprehensive approach to this problem has led to a full electronic chart for conformal radiation therapy treatments.

Data Display↗