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Biomedical subjects

J Jaeger

Publications and source records attributed to J Jaeger.

At least 19 recordsLinked to original sources
PubMed2003

Improved gene selection for classification of microarrays.

In this paper we derive a method for evaluating and improving techniques for selecting informative genes from microarray data. Genes of interest are typically selected by ranking genes according to a test-statistic and then choosing the top k genes. A problem with this approach is that many of these genes are highly correlated. For classification purposes it would be ideal to have distinct but still highly informative genes. We propose three different pre-filter methods--two based on clustering and one based on correlation--to retrieve groups of similar genes. For these groups we apply a test-statistic to finally select genes of interest. We show that this filtered set of genes can be used to significantly improve existing classifiers.

Algorithms↗
PubMed2001

A cellular oscillator model for periodic pattern formation.

In this paper, we present a model for pattern formation in developing organisms that is based on cellular oscillators (CO). An oscillatory process within cells serves as a developmental clock whose period is tightly regulated by cell autonomous or non-autonomous mechanisms. A spatial pattern is generated as a result of an initial temporal ordering of the cell oscillators freezing into spatial order as the clocks slow down and stop at different times or phases in their cycles. We apply a CO model to vertebrate somitogenesis and show that we can reproduce the dynamics of periodic gene expression patterns observed in the pre-somitic mesoderm. We also show how varying somite lengths can be generated with the CO model. We then discuss the model in view of experimental evidence and its relevance to other instances of biological pattern formation, showing its versatility as a pattern generator.

Animals↗
PubMed2001

Sustained suppression of neointimal proliferation by sirolimus-eluting stents: one-year angiographic and intravascular ultrasound follow-up.

BACKGROUND: We have previously reported a virtual absence of neointimal hyperplasia 4 months after implantation of sirolimus-eluting stents. The aim of the present investigation was to determine whether these results are sustained over a period of 1 year. METHODS AND RESULTS: Forty-five patients with de novo coronary disease were successfully treated with the implantation of a single sirolimus-eluting Bx VELOCITY stent in São Paulo, Brazil (n=30, 15 fast release [group I, GI] and 15 slow release [GII]) and Rotterdam, The Netherlands (15 slow release, GIII). Angiographic and volumetric intravascular ultrasound (IVUS) follow-up was obtained at 4 and 12 months (GI and GII) and 6 months (GIII). In-stent minimal lumen diameter and percent diameter stenosis remained essentially unchanged in all groups (at 12 months, GI and GII; at 6 months, GIII). Follow-up in-lesion minimal lumen diameter was 2.28 mm (GIII), 2.32 mm (GI), and 2.48 mm (GII). No patient approached the >/=50% diameter stenosis at 1 year by angiography or IVUS assessment, and no edge restenosis was observed. Neointimal hyperplasia, as detected by IVUS, was virtually absent at 6 months (2+/-5% obstruction volume, GIII) and at 12 months (GI=2+/-5% and GII=2+/-3%). CONCLUSIONS: This study demonstrates a sustained suppression of neointimal proliferation by sirolimus-eluting Bx VELOCITY stents 1 year after implantation.

Blood Vessel Prosthesis Implantation↗
PubMed2001

Molecular basis for the inhibition of Drosophila eye development by Antennapedia.

Hox genes encoding homeodomain transcriptional regulators are known to specify the body plan of multicellular organisms and are able to induce body plan transformations when misexpressed. These findings led to the hypothesis that duplication events and misexpression of Hox genes during evolution have been necessary for generating the observed morphological diversity found in metazoans. It is known that overexpressing Antennapedia (Antp) in the head induces antenna-to-leg as well as head-to-thorax transformation and eye reduction. At present, little is known about the exact molecular mechanism causing these phenotypes. The aim of this study is to understand the basis of inhibition of eye development. We demonstrate that Antp represses the activity of the eye regulatory cascade. By ectopic expression, we show that Antp antagonizes the activity of the eye selector gene eyeless. Using both in vitro and in vivo experiments, we demonstrate that this inhibitory mechanism involves direct protein-protein interactions between the DNA-binding domains of EY and ANTP, resulting in mutual inhibition.

Animals↗
PubMed2001

Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries: a quantitative coronary angiography and three-dimensional intravascular ultrasound study.

BACKGROUND: Restenosis remains an important limitation of interventional cardiology. Therefore, we aimed to determine the safety and efficacy of sirolimus (a cell-cycle inhibitor)-coated BX Velocity stents. METHODS AND RESULTS: Thirty patients with angina pectoris were electively treated with 2 different formulations of sirolimus-coated stents (slow release [SR], n=15, and fast release [FR], n=15). All stents were successfully delivered, and patients were discharged without clinical complications. Independent core laboratories analyzed angiographic and 3D volumetric intravascular ultrasound data (immediately after procedure and at 4-month follow-up). Eight-month clinical follow-up was obtained for all patients. There was minimal neointimal hyperplasia in both groups (11.0+/-3.0% in the SR group and 10.4+/-3.0% in the FR group, P:=NS) by ultrasound and quantitative coronary angiography (in-stent late loss, 0.09+/-0.3 mm [SR] and -0.02+/-0.3 mm [FR]; in-lesion late loss, 0.16+/-0.3 mm [SR] and -0.1+/-0.3 mm [FR]). No in-stent or edge restenosis (diameter stenosis >or=50%) was observed. No major clinical events (stent thrombosis, repeat revascularization, myocardial infarction, or death) had occurred by 8 months. CONCLUSIONS: The implantation of sirolimus-coated BX Velocity stents is feasible and safe and elicits minimal neointimal proliferation. Additional placebo-controlled trials are required to confirm these promising results.

Aged↗
PubMed2001

Association of resident coverage with cost, length of stay, and profitability at a community hospital.

OBJECTIVE: The effect of care by medical residents on hospital length of stay (LOS), indirect costs, and reimbursement was last examined across a range of illnesses in 1981; the issue has never been examined at a community hospital. We studied resource utilization and reimbursement at a community hospital in relation to the involvement of medical residents. DESIGN: This nonrandomized observational study compared patients discharged from a general medicine teaching unit with those discharged from nonteaching general medical/surgical units. SETTING: A 620-bed community teaching hospital with a general medicine teaching unit (resident care) and several general medicine nonteaching units (no resident care). PATIENTS: All medical discharges between July 1998 and February 1999, excluding those from designated subspecialty and critical care units. MEASUREMENTS AND MAIN RESULTS: Endpoints included mean LOS in excess of expected LOS, mean cost in excess of expected mean payments, and mean profitability (payments minus total costs). Observed values were obtained from the hospital's database and expected values from a proprietary risk-cost adjustment program. No significant difference in LOS between 917 teaching-unit patients and 697 nonteaching patients was demonstrated. Costs averaged $3,178 (95% confidence interval (CI) +/- $489) less than expected among teaching-unit patients and $4,153 (95% CI +/- $422) less than expected among nonteaching-unit patients. Payments were significantly higher per patient on the teaching unit than on the nonteaching units, and as a result mean, profitability was higher: $848 (95% CI +/- $307) per hospitalization for teaching-unit patients and $451 (95% CI +/- $327) for patients on the nonteaching units. Teaching-unit patients of attendings who rarely admitted to the teaching unit (nonteaching attendings) generated an average profit of $1,299 (95% CI +/- $613), while nonteaching patients of nonteaching attendings generated an average profit of $208 (95% CI +/- $437). CONCLUSIONS: Resident care at our community teaching hospital was associated with significantly higher costs but also with higher payments and greater profitability.

Hospital Charges↗
PubMed2000

Available pathways database (APD): an essential resource for combinatorial biology.

A relational database, the Available Pathways Database (APD), has been constructed of microbial natural products, their producing strains, and their biosynthetic pathways. The database allows the ready selection of donor strains for combinatorial biology experiments. It provides the same type of resource for combinatorial biology as the Available Chemicals Directory (ACD) does for combinatorial chemical library generation. Its cataloging ability can also provide insight into novel aspects of biosynthetic routes. In particular, no 10-unit Type I polyketides were found in the compilation of this edition of the APD (Version I).

Bacteria↗
PubMed2000

Gasless versus conventional laparoscopy.

The objective of our study was to evaluate the technical advantages of using the Laparolift device and examine the clinical benefits of gynecologic laparoscopy without pneumoperitoneum. A randomized single-blinded clinical trial was performed employing a sample of 30 consecutive patients undergoing laparoscopic gynecologic surgery with a primary outcome measure of visualization. Visualization was found to be inferior in gasless patients. The conclusion was that conventional laparoscopy employing pneumoperitoneum provides surgical exposure superior to that offered by the Laparolift device.

Adult↗
PubMed1999

A new primate from the Middle Eocene of Myanmar and the Asian early origin of anthropoids.

A new genus and species of anthropoid primate, Bahinia pondaungensis gen. et sp. nov., is described from the Yashe Kyitchaung locality in the Late Middle Eocene Pondaung Formation (Myanmar). It is related to Eosimias, but it is represented by more complete remains, including upper dentition with associated lower jaw fragment. It is interpreted as a new representative of the family Eosimiidae, which corresponds to the sister group of the Amphipithecidae and of all other anthropoids. Eosimiidae are now recorded from three distinct Middle Eocene localities in Asia, giving support to the hypothesis of an Asian origin of anthropoids.

Animals↗
PubMed1999

The active site base controls cofactor reactivity in Escherichia coli amine oxidase: x-ray crystallographic studies with mutational variants.

Amine oxidases utilize a proton abstraction mechanism following binding of the amine substrate to the C5 position of the cofactor, the quinone form of trihydroxyphenylalanine (TPQ). Previous work [Wilmot, C. M., et al. (1997) Biochemistry 36, 1608-1620] has shown that Asp383 in Escherichia coliamine oxidase (ECAO) is the catalytic base which performs the key step of proton abstraction. This paper explores in more depth this and other roles of Asp383. The crystal structures of three mutational variants are presented together with their catalytic properties, visible spectra, and binding properties for a substrate-like inhibitor, 2-hydrazinopyridine (2-HP), in comparison to those of the wild type enzyme. In wild type ECAO, the TPQ is located in a wedge-shaped pocket which allows more freedom of movement at the substrate binding position (C5) than for TPQ ring carbons C1-C4. A role of Asp383, whose carboxylate is located close to O5, is to stabilize the TPQ in its major conformation in the pocket. Replacement of Asp383 with the isostructural, but chemically distinct, Asn383 does not affect the location or dynamics of the TPQ cofactor significantly, but eliminates catalytic activity and drastically reduces the affinity for 2-HP. Removal of the side chain carboxyl moiety, as in Ala383, additionally allows the TPQ the greater conformational flexibility to coordinate to the copper, which demonstrates that Asp383 helps maintain the active site structure by preventing TPQ from migrating to the copper. Glu383 has a greatly decreased catalytic activity, as well as a decreased affinity for 2-HP relative to that of wild type ECAO. The electron density reveals that the longer side chain of Glu prevents the pivotal motion of the TPQ by hindering its movement within the wedge-shaped active site pocket. The results show that Asp383 performs multiple roles in the catalytic mechanism of ECAO, not only in acting as the active site base at different stages of the catalytic cycle but also in regulating the mobility of the TPQ that is essential to catalysis.

Amine Oxidase (Copper-Containing)↗
PubMed1998

The structure of HIV-1 reverse transcriptase complexed with an RNA pseudoknot inhibitor.

Small RNA pseudoknots, selected to bind human immunodeficiency virus type 1 (HIV-1) reverse transcriptase tightly, are potent inhibitors of reverse transcriptase. The co-crystal structure of reverse transcriptase complexed with a 33 nucleotide RNA pseudoknot has been determined by fitting the ligand into a high quality, 4-fold averaged 4.8 A resolution electron density map. The RNA is kinked between stems S1 and S2, thereby optimizing its contacts with subunits of the heterodimer. Its binding site extends along the cleft that lies between the polymerase and RNase H active sites, partially overlaps with that observed for duplex DNA and presumably overlaps some portion of the tRNA site. Stem S2 and loop L1 stabilize the 'closed' conformation of the polymerase through extensive electrostatic interactions with several basic residues in helix I of the p66 thumb and in the p66 fingers domain. Presumably, this RNA ligand inhibits reverse transcriptase by binding to a site that partly overlaps the primer-template binding site.

Crystallization↗
PubMed1997

Immune response to Escherichia coli O157:H7 in hemolytic uremic syndrome following salmonellosis.

Escherichia coli O157:H7, a Shiga-like toxin (SLT)-producing enteric pathogen, has been implicated in most cases of post-diarrheal hemolytic uremic syndrome (D + HUS). Infection with other bacterial pathogens such as Salmonella has also preceded D + HUS episodes, leading to speculation that these organisms may also be etiological. We present two children with unrelated D + HUS following salmonellosis. Both children had negative stool cultures on sorbitol-MacConkey agar soon after the onset of diarrhea. After the diagnosis of HUS, both patients had repeat stool cultures positive for Salmonella alone. Polymerase chain reactions for SLT I and II gene sequences in Salmonella isolates were negative. Enzyme-linked immunosorbent assay for specific humoral response to E. coli O157:H7 lipopolysaccharide in acute and convalescent serum samples revealed evidence of heretofore undetected E. coli O157:H7 infection contemporaneous with each D + HUS episode. These cases demonstrate that isolation of only non-SLT-producing microbes from children with D + HUS should raise suspicion of concurrent undetected infection with SLT-producing organisms. Assaying specific immune response to E. coli O157:H7 can be an important epidemiological adjunct. Bacterial infection with non-SLT-producing Salmonella may represent concomitant enteric pathology rather than D + HUS-instigating infection.

Antibodies, Bacterial↗
PubMed1997

Structural and mechanistic consequences of polypeptide binding by GroEL.

The remarkable ability of the chaperonin GroEL to recognise a diverse range of non-native states of proteins constitutes one of the most fascinating molecular recognition events in protein chemistry. Recent structural studies have revealed a possible model for substrate binding by GroEL and a high-resolution image of the GroEL-GroES folding machinery has provided important new insights into our understanding of the mechanism of action of this chaperonin. Studies with a variety of model substrates reveal that the binding of substrate proteins to GroEL is not just a passive event, but can result in significant changes in the structure and stability of the bound polypeptide. The potential impact of this on the mechanism of chaperonin-assisted folding is not fully understood, but provides exciting scope for further experiment.

Amino Acid Sequence↗
PubMed1995

School-based AIDS education for adolescents.

PURPOSE: To describe a program which utilizes medical students and persons with AIDS (PWAs) to provide for adolescents school-based education about acquired immunodeficiency syndrome (AIDS). METHODS: Two 1.5 hour classroom sessions were conducted by medical students and persons with AIDS for seventh and eighth grade students (n = 1,161 students) at two urban middle schools. In addition, a two hour informational session was provided for parents. A 49 question student health survey was used to evaluate adolescents' HIV knowledge, tolerance of persons with AIDS, and intentions to engage in human immunodeficiency virus (HIV) safe behaviors. RESULTS: Significant (p < 0.01) increases in HIV knowledge and tolerance of persons with AIDS were observed, which persisted for three months. A significant (p < 0.01) improvement in intention to engage in HIV-safe behaviors was observed but did not persist for three months. CONCLUSIONS: Medical students and persons with AIDS can provide school-based AIDS education to early adolescents.

Acquired Immunodeficiency Syndrome↗