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PubMed2003

Recurrence of mild malformations and dysplasias.

OBJECTIVE: To estimate whether women delivering infants with mild malformations are at increased risk to have a subsequent infant with a mild malformation. METHODS: Both severe and mild malformations detected at birth were cataloged prospectively for 33,701 women with two consecutive singleton births of infants weighing 500 g or more at a tertiary care hospital. Records from a total of 67,402 infants were analyzed from January 1, 1988, through December 31, 2000. Mild malformations and dysplasias were defined to include skin lesions (eg, café au lait spots, nevi, and hemangiomas), extra nipples, and abnormalities involving digits. Pearson and McNemar chi(2) statistics and analysis of variance were used for statistical analysis. Estimation of recurrence risks was accomplished using standard methods for rates and proportions. RESULTS: Of the study women, 2.7% delivered infants with mild malformations in their index pregnancy. Mild malformations recurred in 7% of women whose index infant had a mild malformation (2.7% versus 7%, P <.001). Mild malformations involving the skin or digits also significantly increased in the next delivery (2% versus 5%, P <.001; 0.5% versus 8%, P <.001; recurrence of skin and digit anomalies, respectively). CONCLUSION: Women delivering infants with mild malformations involving the skin and digits of the infant are at increased risk for recurrence during their next pregnancy.

Congenital Abnormalities↗
PubMed2001

Transgenic and knockout databases: behavioral profiles of mouse mutants.

Genetically engineered strains of mice, modified by transgenesis or gene targeting ("knockouts") are being generated at an impressive rate and used, among other areas, as premiere research tools in deciphering the genetic basis of behavior. As behavioral phenotyping strategies continue to evolve, characterization of these "designer" mice will provide models to evaluate the efficacy of new pharmacological and gene therapy treatments in human hereditary diseases. Reported behavioral profiles include aberrant social, reproductive, and parental behaviors, learning and memory deficits, feeding disorders, aggression, anxiety-related behaviors, pain/analgesia, and altered responses to antidepressants, antipsychotics, ethanol, and psychostimulant drugs of abuse. The Induced Mutant Resource (IMR) at The Jackson Laboratory (TJL, Bar Harbor, ME, USA) imports, cryopreserves, develops, maintains, and distributes biomedically important stocks of transgenic and targeted mutant mice to the research community. Information on neurological/behavioral strains--including behavioral performance, husbandry requirements, strain availability, and genetic typing protocols--is provided through the IMR database (http://www.jax.org/resources/documents/imr/). A catalog of available strains is readily accessible via the JAX Mice website at http://jaxmice.jax.org/index.shtml. In addition, TJL is now host to TBASE (http://tbase.jax.org/), a comprehensive, public-domain database with primary emphasis on mouse knockouts. TBASE contains an exhaustive list of knockout-related citations and provides an extensive phenotypic characterization of numerous behavioral mutants that is extracted directly from the literature. Present efforts to merge the two resources into a novel, schematically enhanced database, provisionally named Transgenic and Targeted Mutation Database (TTMD), will be briefly discussed.

Animals↗
PubMed2000

Integration of cytogenetic data with genome maps and available probes: present status and future promise.

The National Cancer Institute has established an initiative, called the Cancer Chromosome Aberration Project (Ccap), in order to link and integrate the physical and genetic maps of the human genome with cytogenetic data and the location of chromosomal rearrangements in human diseases. This goal will be achieved by high-resolution fluorescence in situ hybridization (FISH) mapping of colony-purified bacterial artificial chromosome (BAC) clones spaced at 1-to 2-Mb intervals across the entire genome. All BAC clones will be anchored on the physical map by the presence of a mapped sequence tagged site (STS). The generation of a publicly accessible clone repository will allow convenient distribution of these BACs. Ccap data can be correlated with other cancer-associated and genomic databases, such as the catalog of chromosomal aberrations in cancer and the emerging full genomic sequence. We anticipate that the use of Ccap clones will expedite and refine the mapping of chromosomal breakpoints. The eventual set of approximately 3,000 Ccap BACs should facilitate the production of BAC-containing DNA chips for assessing copy number of genomic segments by matrix comparative genomic hybridization. In addition, the repository will provide genome-wide tools for defining chromosomal aberrations in cytological specimens by interphase cytogenetics. The Ccap Web site illustrates goals and progress of this initiative (http://www.ncbi.nlm.nih.gov/CCAP/).

Chromosome Mapping↗
PubMed2002

Evolution of cannibalistic traits: scenarios derived from adaptive dynamics.

The evolution of cannibalistic traits in consumer populations is studied in this paper with the approach of adaptive dynamics theory. The model is kept at its minimum complexity by eliminating some environmental characteristics, like heterogeneity and seasonalities, and by hiding the size-structure of the population. Evolutionary dynamics are identified through numerical bifurcation analysis, applied both to the ecological (resident-mutant) model and to the canonical equation of adaptive dynamics. The result is a rich catalog of evolutionary scenarios involving evolutionary stable strategies and branching points both in the monomorphic and dimorphic dynamics. The possibility of evolutionary extinction of highly cannibalistic populations is also ascertained. This allows one to explain why cannibalism can be a transient stage of evolution.

Adaptation, Physiological↗
PubMed2001

An internet database of crotaline venom found in the United States.

Many snake venoms have been shown to be complex mixtures of pharmacologically important molecules, some of which have potential therapeutic value in the treatment of clot-induced ischemia, cancer and other human disorders. The literature contains many references on how venom and/or venom components are being used in medicine. Within the United States, there are 44 subspecies of poisonous snakes. Despite this rather vast diversity, 90% of the venom-related biomedical research conducted on native snakes found in the United States has been done on a limited number of the more common species. Since the venoms from most of the native species are not available or characterized, their composition and potential usefulness in medicine and applied biomedical research has not been explored. The Natural Toxins Research Center (NTRC) at Texas A&M University-Kingsville has developed a serpentarium that presently houses a population of over 250 snakes composed of 11 species and 20 subspecies. These snakes are cataloged on the Internet database along with their geographical location data, proteolytic activities, high performance liquid chromatography (HPLC) and electrophoretic titration (ET) profiles. Many of these snake venoms have never been characterized and few locale-specific differences within a species have been examined. These venoms can be queried through an on-line search routine. The database will be a useful starting point for anyone interested in isolating fibrinolytic enzymes, specific toxins, hemorrhagins, or other pharmacologically active proteins from snake venoms.

Animals↗
PubMed1999

The role of convexity in perceptual completion: beyond good continuation.

Since the seminal work of the Gestalt psychologists, there has been great interest in understanding what factors determine the perceptual organization of images. While the Gestaltists demonstrated the significance of grouping cues such as similarity, proximity and good continuation, it has not been well understood whether their catalog of grouping cues is complete--in part due to the paucity of effective methodologies for examining the significance of various grouping cues. We describe a novel, objective method to study perceptual grouping of planar regions separated by an occluder. We demonstrate that the stronger the grouping between two such regions, the harder it will be to resolve their relative stereoscopic depth. We use this new method to call into question many existing theories of perceptual completion (Ullman, S. (1976). Biological Cybernetics, 25, 1-6; Shashua, A., & Ullman, S. (1988). 2nd International Conference on Computer Vision (pp. 321-327); Parent, P., & Zucker, S. (1989). IEEE Transactions on Pattern Analysis and Machine Intelligence, 11, 823-839; Kellman, P. J., & Shipley, T. F. (1991). Cognitive psychology, Liveright, New York; Heitger, R., & von der Heydt, R. (1993). A computational model of neural contour processing, figure-ground segregation and illusory contours. In Internal Conference Computer Vision (pp. 32-40); Mumford, D. (1994). Algebraic geometry and its applications, Springer, New York; Williams, L. R., & Jacobs, D. W. (1997). Neural Computation, 9, 837-858) that are based on Gestalt grouping cues by demonstrating that convexity plays a strong role in perceptual completion. In some cases convexity dominates the effects of the well known Gestalt cue of good continuation. While convexity has been known to play a role in figure/ground segmentation (Rubin, 1927; Kanizsa & Gerbino, 1976), this is the first demonstration of its importance in perceptual completion.

Cues↗
PubMed2002

AGEID: a database of aging genes and interventions.

The aging genes/interventions database (AGEID) is a database of experimental results related to aging. AGEID is available as part of the science of aging knowledge environment on the World Wide Web at http://sageke.sciencemag.org/cgi/genesdb. The goal of AGEID is to catalog, in one location, every published experiment where life span has been measured in any organism. AGEID also includes information on genes that influence the incidence of age-associated disorders such as Alzheimer's disease and Parkinson's disease. AGEID gene/intervention reports are formatted pages containing the organism and strain background in which the particular experiment was performed, the type of genetic or environmental perturbation, the effect on life span, a description of the gene function and its role in longevity, protein homologs, and references. The use of this database by researchers who study aging should facilitate easy comparison of the genes and interventions that affect life span in different organisms.

Aging↗
PubMed2001

The lod score method.

The lod score method originated in a seminal article by Newton Morton in 1955. The method is broadly concerned with issues of power and the posterior probability of linkage, ensuring that a reported linkage has a high probability of being a true linkage. In addition, the method is sequential, so that pedigrees or lod curves may be combined from published reports to pool data for analysis. This approach has been remarkably successful for 50 years in identifying disease genes for Mendelian disorders. After discussing these issues, we consider the situation for complex disorders, where the maximum lod score (MLS) statistic shares some of the advantages of the traditional lod score approach but is limited by unknown power and the lack of sharing of the primary data needed to optimally combine analytic results. We may still learn from the lod score method as we explore new methods in molecular biology and genetic analysis to utilize the complete human DNA sequence and the cataloging of all human genes.

Genetic Linkage↗
PubMed2003

Studying large viruses.

In this article we have attempted to describe some structural aspects of large viruses. Although this may seem a straightforward task, it is complicated by the fact that large viruses do not represent a distinctive class of organisms and any grouping under this heading will include a range of unrelated viruses with different structures, replication strategies, and host types. To simplify matters we limited our definition to dsDNA viruses with genomes of 100 kbp or larger. However, even this restricted grouping includes viruses with diverse and seemingly unrelated structures. Furthermore, few if any structural features are exclusive to large viruses and most of what appears distinctive about their structure or assembly can also be found in smaller, and usually better characterized, viruses. Therefore we have not attempted to provide a comprehensive catalog of the properties of large viruses but have tried to illustrate particular structural points with examples from a few of the better known forms, notably herpes simplex virus (HSV) and phage T4. The two techniques used to provide rigorous analyses of virus structures are X-ray crystallography and electron cryomicroscopy with computer-assisted reconstruction. To date, X-ray crystallography has been successful only with smaller viruses, and what is known about the structures of these large viruses has come primarily from electron cryomicroscopy. However, with the notable exception of the HSV capsid, such studies have been limited in extent and of relatively low resolution, and the information obtained has been confined largely to describing the spatial distributions and relationships between the subunits. Nevertheless, these studies have given us our clearest insights into the biology of these complex particles and increases in resolution promise to extend these insights by bridging the gap between gross and atomic structures, as exemplified by the identification and mapping of secondary structural elements in the HSV capsid.

Genome, Viral↗
PubMed1994

Antisense treatment of viral infection.

In this chapter I have attempted to outline the rationale that underlies the antisense approach to treatment of virus infection, to catalog the effector molecules that are currently available, and to estimate the relative worth of each. In so doing I have tried to describe the criteria that might be employed in their design and the factors that may determine their efficacy in tissue culture and, perhaps, in vivo. Finally, I have described the few examples presently available that indicate that antisense approaches may one day be therapeutically useful in treatment of disease of viral or nonviral origin.

Animals↗
PubMed1989

Human papillomaviruses and carcinomas.

The recognition of multiple types of human papillomaviruses has resulted in remarkable progress in the detection of persisting viral nucleic acid sequences in carcinomas. The consistent transcription in tumors of two early open reading frames, E6 and E7, with few exceptions (Lehn et al., 1985), indicates a role for the products of these genes in the induction and/or maintenance of the transformed state. A number of studies have shown that in vitro transformation can be achieved by transfection of E6/E7 DNA, and proteins encoded by these DNA sequences can be demonstrated in primary human keratinocytes immortalized by this DNA (Kaur et al., 1989). Mutagenesis experiments are needed to determine the absolute requirement for and function of these genes in transformation. A preferential association of some types with benign lesions while others may be frequently found in malignant tumors has been observed. HPV types 5 and 8 in epidermodysplasia verruciformis patients and types 16, 18, 31, 33, etc. in genital lesions are most frequently associated with progression to malignancy, whereas other types, such as HPV-6,-10, -11, and -20, are regularly identified in benign warts. Such distinctions are not absolute but provide the initial steps toward establishing a causal role for some human papillomaviruses in carcinomas. The need for well-designed epidemiological studies in concert with optimum molecular and serologic evaluations is evident (Armstrong et al., 1988). The data from human and animal studies indicate that papillomaviruses contribute significantly to the development of many, if not all, carcinomas, but we do not yet have a clear understanding of the importance of other interacting viral, chemical, or cellular factors. The application of gene cloning and non-stringent hybridization (Law et al., 1979) has provided us with an apparently ever-increasing catalog of human papillomaviruses. More effort is now required to establish their prevalence, the natural history of infection, and the mechanism of neoplastic transformation.

Animals↗
PubMed2002

Phenotype switching in polymorphic Tetrahymena: a single-cell Jekyll and Hyde.

For nearly half a century, phenotype switching in the group of polymorphic species of the ciliate genus Tetrahymena has been the subject of investigations of the underlying mechanisms, the accompanying biochemical and structural changes, and the evolution of polymorphic survival strategy. Beginning with the pioneering systematic studies by Furgason in 1940 of hymenostome ciliates, the experimental approach rapidly expanded to include investigations of growth, nutrition, physiology, morphology, and morphogenesis in the polymorphic species. Recently, with progress in elucidation of the novel signaling ligand and identification of elements of the subsequent signal transduction cascade, in addition to the growing catalog of intracellular events associated with differentiation in these unicellular eukaryotes, we have begun to address the mechanistic basis of polymorphism. This review summarizes and integrates the history and recent discoveries concerning Tetrahymena polymorphic cells. We are now poised to answer fundamental questions about this interesting pathway of cell differentiation.

Animals↗
PubMed1993

The neurobiology and genetics of infantile autism.

Autism is a syndrome with multiple etiologies, as is made clear both by the evidence of neurobiological research and by the catalog of disorders that present with autistic behaviors. What remains unclear are the specific neuropathological mechanisms that produce autistic behaviors; for example, is there a common neuroanatomic pathology for all cases of autism, or can autistic behaviors emerge from different pathological sequences within the brain? Although it is premature to generalize, neuropathological studies appear to have identified common abnormalities in the cerebellum and limbic system of at least five autistic subjects. These subjects, with variable levels of mental retardation, demonstrated marked Purkinje cell loss in the cerebellar hemispheres, together with retained fetal neuronal circuitry in cerebellar nuclei and increased neuronal packing in specific regions of the limbic system, amygdala, and hippocampus. The architecture of the cerebral cortex was not affected. Although our knowledge of brain functioning is incomplete, alterations of the kind noted in the cerebellum and limbic system could reasonably produce autistic behaviors. For more detail, readers are directed to a review of cerebellar contributions to higher functions by Schmahmann (1991). Neuroimaging studies allow less resolution of brain structure than do neuroanatomic studies, and the reported findings from neuroimaging are somewhat contradictory. However, a number of investigators have reported structural abnormalities in ventricle size and cerebral hemispheric asymmetry using CT. MRI, which offers greater resolution, has uncovered some consistent findings, along with a variety of nonspecific abnormalities. Common abnormalities include reduced volume of cerebellar hemispheres and vermal lobules--findings not inconsistent with the above-mentioned neuropathological defects. It is also interesting to note that individuals with fragile X syndrome have similar cerebellar findings. PET and NMR studies of autism are at a preliminary stage, but these methodologies allow insight into the functioning of the brain, rather than simply brain anatomy. Recent PET studies indicating decreased association between paired regions of the brains of autistic subjects are of interest, particularly if they can be confirmed and refined by additional studies. Neurophysiological studies also offer insight into brain function, but are subject to numerous methodological criticisms. Nevertheless, recent reports of diminished P300 waves and absent NC components in autistic subjects seem to indicate fundamental defects in attention and secondary processing, which could help explain the self-stimulatory behaviors often seen in autism. The disturbances in brain development associated with autism can be produced in a number of ways, and at different times during development of the nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)

Autistic Disorder↗
PubMed2006

The Agilent in situ-synthesized microarray platform.

Microarray technology has become a standard tool in many laboratories. Agilent Technologies manufactures a variety of catalog and custom long-oligonucleotide (60-mer) microarrays that can be used in multiple two-color microarray applications. Optimized methods and techniques have been developed for two such applications: gene expression profiling and comparative genomic hybridization. Methods for a third technique, location analysis, are evolving rapidly. This chapter outlines current best methods for using Agilent microarrays, provides detailed instructions for the most recently developed techniques, and discusses solutions to common problems encountered with two-color microarrays.

Animals↗
PubMed1999

Databases in the assessment of the effects of drugs during pregnancy.

There is limited information on the effects of marketed drugs in pregnant women, largely because premarketing studies are not conducted in this population unless the agent is intended for specific use during pregnancy. Current information on the use of available medications during pregnancy includes 3 types of data: (1) case reports, (2) case-control studies, and (3) cohort studies. Assessments of pregnancy risk related to medication use most commonly involve case reports, and each year the Food and Drug Administration catalogs approximately 1000 suspected adverse drug experiences during pregnancy. The Food and Drug Administration, working with Michigan Medicaid, has developed a database of several hundred thousand pregnancy outcomes. Results of this study for asthma medications used between 1980 and 1992 are presented. However, interpretation of the results is complicated, and substantially more data are required, particularly as new medications become available.

Asthma↗
PubMed1999

Evaluation of materials used for bedding encasement: effect of pore size in blocking cat and dust mite allergen.

BACKGROUND: Mattress and pillow encasings are recommended for patients allergic to dust mites. Many encasements block allergen and are vapor permeable but do not allow free passage of air through the material. Recently, breathable fabrics made from tightly woven synthetic fibers or nonwoven synthetics have been recommend as encasements. OBJECTIVE: The purpose of this study was to develop a method for testing encasement materials made of breathable fabrics. METHODS: Dust samples containing a known quantity of allergen (Der f 1, Der p 1, and Fel d 1) were pulled across a variety of fabrics using a modified dust trap. Airflow through the dust trap was controlled with a vacuum pump. Five minutes after dust was introduced, the pump was shut off. A filter located downstream of the fabric collected allergen passing through the fabric during the test and was assayed with ELISA for the relevant allergen. Fabrics to be tested were obtained from manufacturers and specialty catalogs. RESULTS: As the average pore size decreases, the airflow through a fabric becomes restricted, and the pressure differential created by the vacuum pump increases. Dust mite allergens (Der f 1 and Der p 1) were blocked below detectable limits by fabrics of less than 10 microm in pore size. Fabrics with an average pore size of 6 microm or less blocked cat allergen (Fel d 1). CONCLUSION: The method we developed provided a rigorous and reliable test for leakage of common indoor allergens through breathable barrier fabrics. Our results show that tightly woven fabrics and nonwoven synthetic fabrics can block common indoor allergens but still allow airflow.

Allergens↗
PubMedDate not supplied

Morbidity and mortality conference: enhancing delivery of surgery residency curricula.

PURPOSE: To determine the exposure of surgical residents to educational subjects contained in the APDS 2000 Curriculum from a weekly Morbidity and Mortality (M&M) conference. METHODS: The departmental quality assurance data base was queried for content presented in a residency program's M&M conference. The presentation topics, the services involved, and the occurrence causation were all cataloged to assess the extent of material covered. The topic was logged if the case occurrence generated discussion beyond a superficial notation. An attending moderated the discussions, with resident and faculty interaction on causality determination. Imaging studies were available as appropriate to the case discussed. RESULTS: At least 95 discrete topics in 149 separate occurrences were covered in the weekly M&M conference in 1 academic year from July 1999 through June 2000. Common topics included wound infection (9), deep venous thrombosis (7), small bowel obstruction (5), and pulmonary embolus (4). Five topics were discussed 3 times, 23 were discussed twice, and 63 were discussed once. Although many occurrences had multiple causes, Pareto analysis of causation determined that nature of disease was prominent in 78 (52.4%), diagnostic difficulty in 31 (20.8%), technical error in 27 (18.1%), and error in judgment in 13 (8.7%). Pareto analysis of the surgical domains addressed included trauma (37, 24.8%), general surgery (35, 23.5%), common issues independent of service (32, 21.5%), vascular (20, 13.5%), cardio thoracic (11, 7.4%), critical care (9, 6.1%), and all other services (5, 3.4%). CONCLUSIONS: A weekly M&M conference in a residency program provides broad exposure to material contained in the APDS 2000 curriculum. A peer-reviewed M&M conference provides ongoing examination of common problems encountered in the delivery of surgical care. By so doing, it promotes interactive teaching of the most relevant surgical problems.

Journal Article↗
PubMed1994

Ophthalmic findings in scleromyxedema.

PURPOSE: To catalog ophthalmic findings in a cohort of patients with scleromyxedema. METHODS: Thirty-five biopsy-proven patients with scleromyxedema evaluated at the Mayo Clinic in Rochester, Minnesota, from 1960 to 1991 were identified. Eye examinations were performed on 17 of the patients. Ophthalmic findings not attributable to other systemic or ocular disease were recorded. RESULTS: The following abnormalities were considered secondary to scleromyxedema: corneal opacities (2 patients), thickened eyebrow or eyelid skin (4 patients), lagophthalmos (1 patient), and ectropion (2 patients). One patient who had concurrent polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome also had choroidal folds and papilledema. A corneal biopsy in one patient disclosed deposits of acid mucopolysaccharide, consistent with one of two previously published cases. CONCLUSION: A series of patients with scleromyxedema was reviewed. This systemic disorder infrequently may cause visually significant ophthalmic manifestations, including eyelid changes and corneal deposits. Further study is needed to characterize better the nature of the corneal opacities.

Adult↗