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Biomedical subjects

S Kurtz

Publications and source records attributed to S Kurtz.

At least 19 recordsLinked to original sources

Silencing of death receptor and caspase-8 expression in small cell lung carcinoma cell lines and tumors by DNA methylation.

Small cell lung cancer cell lines were resistant to FasL and TRAIL-induced apoptosis, which could be explained by an absence of Fas and TRAIL-R1 mRNA expression and a deficiency of surface TRAIL-R2 protein. In addition, caspase-8 expression was absent, whereas FADD, FLIP and caspases-3, -7, -9 and -10 could be detected. Analysis of SCLC tumors revealed reduced levels of Fas, TRAIL-R1 and caspase-8 mRNA compared to non-small cell lung cancer (NSCLC) tumors. Methylation-specific PCR demonstrated methylation of CpG islands of the Fas, TRAIL-R1 and caspase-8 genes in SCLC cell lines and tumor samples, whereas NSCLC samples were not methylated. Cotreatment of SCLC cells with the demethylating agent 5'-aza-2-deoxycytidine and IFNgamma partially restored Fas, TRAIL-R1 and caspase-8 expression and increased sensitivity to FasL and TRAIL-induced death. These results suggest that SCLC cells are highly resistant to apoptosis mediated by death receptors and that this resistance can be reduced by a combination of demethylation and treatment with IFNgamma.

Apoptosis↗

Combined perfluoropropane gas and viscoelastic material injection for anterior chamber reformation following trabeculectomy.

AIM: To describe a novel technique to treat hypotony and shallow anterior chamber following trabeculectomy METHODS: Three patients who underwent fornix based trabeculectomy with mitomycin C (MMC) presented in the postoperative days with a shallow anterior chamber, hypotony, and overfiltrating blebs. They were treated with an injection of 0.2 ml of 16% perfluoropropane (C(3)F(8)) to the anterior chamber followed by an injection of a viscoelastic material. RESULTS: In all patients the anterior chamber was reformed successfully without any complications. CONCLUSIONS: Patients with a shallow anterior chamber and overfiltrating blebs following a recent trabeculectomy can be treated successfully with a combination of a long acting gas and a viscoelastic material.

Anterior Chamber↗

REPuter: the manifold applications of repeat analysis on a genomic scale.

The repetitive structure of genomic DNA holds many secrets to be discovered. A systematic study of repetitive DNA on a genomic or inter-genomic scale requires extensive algorithmic support. The REPuter program described herein was designed to serve as a fundamental tool in such studies. Efficient and complete detection of various types of repeats is provided together with an evaluation of significance and interactive visualization. This article circumscribes the wide scope of repeat analysis using applications in five different areas of sequence analysis: checking fragment assemblies, searching for low copy repeats, finding unique sequences, comparing gene structures and mapping of cDNA/EST sequences.

Algorithms↗

HyPaLib: a database of RNAs and RNA structural elements defined by hybrid patterns.

The database, called HyPaLib (for Hybrid Pattern Library), contains annotated structural elements characteristic for certain classes of structural and/or functional RNAs. These elements are described in a language specifically designed for this purpose. The language allows convenient specification of hybrid patterns, i.e. motifs consisting of sequence features and structural elements together with sequence similarity and thermodynamic constraints. We are currently developing software tools that allow a user to search sequence databases for any pattern in HyPaLib, thus providing functionality which is similar to PROSITE, but dedicated to the more complex patterns in RNA sequences. HyPaLib is available at http://bibiserv. techfak.uni-bielefeld.de/HyPa/.

Algorithms↗

A collaborative program for cardiovascular patient follow-up.

Transitions from one health care system to another are common, but they can affect coordination of care and measurement of patient outcomes. In this project, a community hospital and a tertiary center collaborated to obtain follow-up information on patients 30 days after they underwent cardiac catheterization and revascularization. Results show that patients experienced similar physical and emotional concerns regardless of diagnosis or procedure. Although the intent was to gather information, nurses also provided education and arranged services for patients. This project has implications for the development of collaborative interventions to improve care for patients after undergoing coronary procedures.

Aftercare↗

Legionella pneumophila major acid phosphatase and its role in intracellular infection.

Legionella pneumophila is an intracellular pathogen of protozoa and alveolar macrophages. This bacterium contains a gene (pilD) that is involved in both type IV pilus biogenesis and type II protein secretion. We previously demonstrated that the PilD prepilin peptidase is crucial for intracellular infection by L. pneumophila and that the secreted pilD-dependent proteins include a metalloprotease, an acid phosphatase, an esterase/lipase, a phospholipase A, and a p-nitrophenyl phosphorylcholine hydrolase. Since mutants lacking type IV pili, the protease, or the phosphorylcholine hydrolase are not defective for intracellular infection, we sought to determine the significance of the secreted acid phosphatase activity. Three mutants defective in acid phosphatase activity were isolated from a population of mini-Tn10-mutagenized L. pneumophila. Supernatants as well as cell lysates from these mutants contained minimal acid phosphatase activity while possessing normal levels of other pilD-dependent exoproteins. Genetic studies indicated that the gene affected by the transposon insertions encoded a novel bacterial histidine acid phosphatase, which we designated Map for major acid phosphatase. Subsequent inhibitor studies indicated that Map, like its eukaryotic homologs, is a tartrate-sensitive acid phosphatase. The map mutants grew within macrophage-like U937 cells and Hartmannella amoebae to the same degree as did wild-type legionellae, indicating that this acid phosphatase is not essential for L. pneumophila intracellular infection. However, in the course of characterizing our new mutants, we gained evidence for a second pilD-dependent acid phosphatase activity that, unlike Map, is tartrate resistant.

Acid Phosphatase↗

Two nonredundant SecA homologues function in mycobacteria.

The proper extracytoplasmic localization of proteins is an important aspect of mycobacterial physiology and the pathogenesis of Mycobacterium tuberculosis. The protein export systems of mycobacteria have remained unexplored. The Sec-dependent protein export pathway has been well characterized in Escherichia coli and is responsible for transport across the cytoplasmic membrane of proteins containing signal sequences at their amino termini. SecA is a central component of this pathway, and it is highly conserved throughout bacteria. Here we report on an unusual property of mycobacterial protein export--the presence of two homologues of SecA (SecA1 and SecA2). Using an allelic-exchange strategy in Mycobacterium smegmatis, we demonstrate that secA1 is an essential gene. In contrast, secA2 can be deleted and is the first example of a nonessential secA homologue. The essential nature of secA1, which is consistent with the conserved Sec pathway, leads us to believe that secA1 represents the equivalent of E. coli secA. The results of a phenotypic analysis of a Delta secA2 mutant of M. smegmatis are presented here and also indicate a role for SecA2 in protein export. Based on our study, it appears that SecA2 can assist SecA1 in the export of some proteins via the Sec pathway. However, SecA2 is not the functional equivalent of SecA1. This finding, in combination with the fact that SecA2 is highly conserved throughout mycobacteria, suggests a second role for SecA2. The possibility exists that another role for SecA2 is to export a specific subset of proteins.

Adenosine Triphosphatases↗

The wear of oriented UHMWPE under isotropically rough and scratched counterface test conditions.

Unidirectional wear tests of UHMWPE against smooth counterfaces show that molecular chains at the surface of virgin material become oriented parallel to the sliding direction giving low wear rate. It is postulated that under more abrasive conditions and predominantly unidirectional motion as in knee prostheses, it may proof beneficial to provide molecular orientation of the bulk material. Therefore strips of UHMWPE were oriented by die drawing at elevated temperature and the resulting anisotropic material subjected to tensile tests, small punch tests and also unidirectional wear tests both parallel and perpendicular to the draw direction. The tensile tests showed that, in the parallel direction, the oriented UHMWPE became stiffer and less ductile compared to the virgin UHMWPE. In the perpendicular direction, there were reductions in yield stress, 5% proof stress and energy to failure compared to the virgin material. The small punch test showed that the oriented UHMWPE exhibited apparent hardening when tested in both parallel and perpendicular directions but the mechanical behaviour in the perpendicular direction was comparable to the virgin UHMWPE. The wear tests demonstrated that the oriented UHMWPE did not show any significant improvement of wear resistance for sliding against either isotropically rough or scratched counterfaces. There was no clear dependency between the mechanical properties and wear factors of the oriented UHMWPE.

Biocompatible Materials↗

Certification: perspectives on competency assurance.

As registered professional nurses, we have an obligation to our patients to assure we are practicing at a competent level. Nurse managers and administrators must show to the Joint Commission for Accreditation of Healthcare Organization (JCAHO) that the nurses providing care in their facility are competent. Assessing competency is not a simple task, and there is no 1 correct answer or definition of competence or competency assessment. Some of the methods available for competency assessment are self-assessment models, multiple choice examinations used for certification and licensure, oral or essay examinations, and practice or patient simulations. The Certification Board Perioperative Nursing (CBPN) recognizes that learning and competency maintenance is accomplished in a variety of ways, and that learning is achieved through successful participation in various professional activities. Becoming certified and remaining certified, or completion of the Professional Perioperative Portfolio are ways for nurses to continue to show competency in perioperative nursing. Research is vital to validate that certification does indeed show competency. The research committee of CBPN and the Nurse Credentialing Research Coalition (NCRC) are committed to quantify not only the value of the credential but to examine the personal, professional, and practice outcomes of certified nurses across the country. It is hoped that the current research being conducted will eventually allow concerned parties to have assurance that the certified professional registered nurse is indeed a competent registered nurse.

Certification↗

[Early detection of glaucoma by a mobile unit--results from 10,000 examinees].

Glaucoma, the third leading cause of blindness in the western world, is characterized by painless, gradual loss of visual fields which may lead to severe visual impairment or even blindness. In 4 years of operation of a mobile glaucoma unit for screening and early diagnosis of glaucoma, 10,037 subjects aged 18-95 years were screened (4504 women, 45%); 55% were under 50 years (Graph 1). Ocular hypertension was diagnosed in 8.0%; primary open angle glaucoma (POAG) in 0.8%, with 2/3 already under treatment, the rest newly diagnosed. Pseudo-exfoliative glaucoma was diagnosed in 0.2%; only 2 cases had closed angle glaucoma; 91% of those screened were normal (Fig. 4; age stratification, Graph 3). POAG increased with age, from 0.2% in those under 40 years to 10% in those over 80; POAG was more common in men, but OHT was similar in both sexes (6.0% vs. 5.3%). There was no correlation between incidence of POAG and place of work except in the Sorek Nuclear Center (1.9% vs. 0.8%, p = 0.11). Other conditions significantly more frequent in POAG than normals were diabetes mellitus (x 2.5), systemic hypertension (x 4), myopia (x 2) and history of intraocular surgery (x 6).

Adolescent↗

Prism induced accommodation in infants 3 to 6 months of age.

Convergence-accommodation, one of several cross-linkages in the oculomotor system is manifested by opening the accommodative feedback loop and increasing the vergence input. We elicited this response in human infants aged 3-6 months by placing a 15 delta prism (base-out) before one eye while they viewed a diffuse patch of light. Accommodation was measured and ocular alignment was confirmed with a video photorefractor. The convergence-accommodation response is therefore present during a time when blur driven accommodation and disparity vergence are maturing. The gain of convergence-accommodation (expressed as the stimulus CA/C ratio) appeared to be greater for infants than adults.

Accommodation, Ocular↗

The role of angiotensin converting enzyme and angiotensin II type 1 receptor gene polymorphisms in patients with nonarteritic anterior ischemic optic neuropathy.

OBJECTIVE: To determine the role of angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) polymorphisms in the pathogenesis of nonartertic anterior ischemic optic neuropathy (NAION). DESIGN: Retrospective, case-control study. PARTICIPANTS: Seventy-four patients with NAION diagnosed from 1984 through 1999. Seventy-one patients who visited the Eye Institute comprised the control group. TESTING INTERVENTION: DNA was extracted from whole blood obtained from all patients and control participants. Polymerase chain reaction (PCR) was used for analysis of ACE and AT1R polymorphisms. RESULTS: The frequency of the polymorphism for ACE among the NAION patients (39.2% deletion allele [DD], 54.0% deletion/insertion [D/I] locus, 6.8% insertion allele [II]) was similar to that of the control group (50.7% DD, 39.4% D/I, 9.9% II), with P = 0.21. The frequency of the polymorphism of AT1R in the NAION patients was 5.4% CC, 44.6% CA, 50% AA, and in the control group it was 4.2% CC, 33.8% CA, 62.0% AA, with P = 0.35. Participants less than 55 years of age and those more than 55 had quite similar distributions. CONCLUSIONS: Angiotensin converting enzyme and AT1R polymorphisms have no part in the mechanism of NAION. Thus drugs such as ACE inhibitors or AT1R antagonists are not specifically indicated for treatment of these patients.

Adult↗

Secreted enzymatic activities of wild-type and pilD-deficient Legionella pneumophila.

Legionella pneumophila, the agent of Legionnaires' disease, is an intracellular pathogen of protozoa and macrophages. Previously, we had determined that the Legionella pilD gene is involved in type IV pilus biogenesis, type II protein secretion, intracellular infection, and virulence. Since the loss of pili and a protease do not account for the infection defect exhibited by a pilD-deficient strain, we sought to define other secreted proteins absent in the mutant. Based upon the release of p-nitrophenol (pNP) from p-nitrophenyl phosphate, acid phosphatase activity was detected in wild-type but not in pilD mutant supernatants. Mutant supernatants also did not release either pNP from p-nitrophenyl caprylate and palmitate or free fatty acid from 1-monopalmitoylglycerol, suggesting that they lack a lipase-like activity. However, since wild-type samples failed to release free fatty acids from 1,2-dipalmitoylglycerol or to cleave a triglyceride derivative, this secreted activity should be viewed as an esterase-monoacylglycerol lipase. The mutant supernatants were defective for both release of free fatty acids from phosphatidylcholine and degradation of RNA, indicating that PilD-negative bacteria lack a secreted phospholipase A (PLA) and nuclease. Finally, wild-type but not mutant supernatants liberated pNP from p-nitrophenylphosphorylcholine (pNPPC). Characterization of a new set of mutants defective for pNPPC-hydrolysis indicated that this wild-type activity is due to a novel enzyme, as opposed to a PLC or another known enzyme. Some, but not all, of these mutants were greatly impaired for intracellular infection, suggesting that a second regulator or processor of the pNPPC hydrolase is critical for L. pneumophila virulence.

Bacterial Proteins↗

Computation and visualization of degenerate repeats in complete genomes.

The repetitive structure of genomic DNA holds many secrets to be discovered. A systematic study of repetitive DNA on a genomic or inter-genomic scale requires extensive algorithmic support. The REPuter family of programs described herein was designed to serve as a fundamental tool in such studies. Efficient and complete detection of various types of repeats is provided together with an evaluation of significance, interactive visualization, and simple interfacing to other analysis programs.

Algorithms↗

Spiral Density Wave Shock-induced Star Formation at High Galactic Latitudes.

We have modeled the gas response to a spiral density wave (SDW) in a thick, magnetized galactic disk. The inclusion in the model of the vertically extended galactic warm ionized gas layer alters the conventional view of the SDW scenario for star formation: whereas marked density enhancements still occur in the midplane, the shock and a prominent high column density structure extend to high z (the height above the galactic midplane) above the arm. We argue that if the SDW mechanism indeed triggers molecular cloud and star formation, it should do so not only at the midplane but also at distances well above the star-forming thin disk of the conventional picture. The resulting structure resembles a hydraulic jump, or bore, in which gas entering the spiral arm rises suddenly on the upstream side of the arm, then accelerates and angles downward, finally landing on a large downfall region downstream of the arm.

Journal Article↗

Analysis of prothrombotic and vascular risk factors in patients with nonarteritic anterior ischemic optic neuropathy.

OBJECTIVE: To determine whether genetic or acquired thrombophilias and other risk factors are associated with nonarteritic anterior ischemic optic neuropathy (NAION). DESIGN: Retrospective case-control study. PARTICIPANTS: Sixty-one patients with NAION diagnosed between 1984 and 1997. Ninety consecutive patients who visited the Eye Institute made up the control group. INTERVENTION: Protein C, protein S, antithrombin III, lupus anticoagulant, and three recently described prothrombotic polymorphisms (i.e., factor V G1691A, factor II G20210A, and methylenetetrahydrofolate reductase [MTHFR] C677T) were analyzed. In addition, risk factors for arteriosclerotic vascular disease were assessed. MAIN OUTCOME MEASURES: Parameters of thrombophilia. RESULTS: None of the thrombophilic markers (genetic and acquired) constituted a significant risk factor for NAION. Ischemic heart disease, hypercholesterolemia, and diabetes mellitus were discerned as risk factors for NAION with odds ratios of 2.9 (95% confidence interval [CI], 1.3-6.4), 2.6 (95% CI, 1.2-5.5), and 2.3 (95% CI, 1.1-4.8), respectively. Multiple logistic regression analysis indicated that ischemic heart disease and hypercholesterolemia exerted an additive risk for NAION with a combined odds ratio of 4.5 (95% CI, 1.4-14.5). However, none of these risk factors statistically predicted second eye involvement. CONCLUSION: NAION was not found to be associated with thrombophilic risk factors, yet it was related to ischemic heart disease, hypercholesterolemia, and diabetes mellitus.

Adult↗

Informed consent and general surgeons' attitudes toward the use of pain medication in the acute abdomen.

To determine general surgeons' attitudes about the use of pain medications in the acute abdomen, a questionnaire was mailed to all practicing general surgeons in Iowa. The questionnaire sought to determine the frequency with which pain medications were administered either before informed consent was obtained or before the patient with an acute abdomen was examined, and, in cases when pain medications were withheld, the reasons for withholding. The response rate was 72% (131 of 182). Seven percent of patients with an acute abdomen received pain medications by a general surgeon before being seen and 22% received pain medication by another physician in the emergency department (ED). Fifty-three percent of general surgeons responded that they believe pain medications preclude a patient from signing a valid informed consent; 78% reported that concerns about informed consent enter into their decision to withhold pain medications. Sixty-seven percent agreed that pain medications interfere with diagnostic accuracy, and 82% consider diagnostic accuracy when deciding to withhold pain medication.

Abdomen, Acute↗