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PubMed1994

An analysis of market shares of Maryland hospitals in their service areas.

The study analyzes market shares (or competitiveness) of Maryland hospitals based on a service area definition of hospitals used for acute care planning in Maryland. The study uses this service area definition to analyze market shares of Maryland hospitals, to test them under alternative hypotheses and, finally, to examine the impact of several key variables. The study finds that proximity of other hospitals, and hospital's occupied bed size, have statistically significant impacts on market shares of hospitals irrespective of hospital location in a metropolitan or rural area.

Bed Occupancy↗

PubMed1998

Level of heteroplasmy for the mitochondrial mutation A3243G correlates with age at onset of diabetes and deafness.

The mitochondrial mutation A3243G has been shown to be associated with a syndrome of diabetes mellitus and sensorineural hearing loss. Using a solid-phase-based sequencing method we have investigated the relation between the proportion of mutant mitochondrial genomes and the time of disease onset among members of three families where the mutation segregates. A striking association was observed between the level of heteroplasmy and time of onset of disease, particularly hearing loss. Accordingly, this syndrome shares features of diseases caused by dynamic mutations in that variable transmission of the level of heteroplasmy between generations influences disease severity.

Adolescent↗

PubMed2005

Antiferritin antibodies discovered by phage display expression cloning are associated with radiographic damage in rheumatoid arthritis.

OBJECTIVE: Several autoantibodies have been described in individuals with rheumatoid arthritis (RA), leading to interest in the use of such antibodies as diagnostic or prognostic markers in RA as well as in their relevance to disease pathology. The objective of this study was to use a phage display expression cloning system to identify novel autoantibody targets in RA. METHODS: We used immunoscreening of a phage-displayed complementary DNA (cDNA) library to isolate a cDNA clone encoding the ferritin heavy chain polypeptide. Antiferritin antibody levels in patients with early and established RA, healthy controls, and disease controls were measured by enzyme-linked immunosorbent assay. Antibody-positive and antibody-negative individuals were compared with respect to disease severity as measured by the modified Larsen score, demographic variables, rheumatoid factor status, and carriage of HLA-DRB1 shared epitope alleles. RESULTS: Antiferritin antibodies were present in 60 (16%) of 366 patients with established RA, 23 (19%) of 118 patients with early RA, 2 (2.7%) of 73 healthy blood donors, 2 (2.1%) of 94 individuals with osteoarthritis, and 2 (2.1%) of 97 patients with systemic lupus erythematosus (P < 0.01, RA patients versus healthy and disease controls). Antiferritin antibodies were more common in men than in women (28.4% versus 12.2%; P < 0.001), and antiferritin levels were associated with the severity of joint damage (P = 0.01). CONCLUSION: Antiferritin antibodies are observed in a subset of patients with RA, are present early in the disease course, and are associated with the severity of radiographic damage. Further studies are required to explore their potential as diagnostic and prognostic markers in RA.

Adult↗

PubMed2002

The psychology of telling murder stories: do we think in scripts, exemplars, or prototypes?

According to the story model of Pennington and Hastie, jurors collect information at trial and modify it with general knowledge to create case stories. Schank and Ableson argue that human memory is organized to tell and understand stories. However, Finkel and Groscup questioned the use of manipulated, experimenter-constructed narratives to demonstrate the existence of multiple prototypical crime stories. We interviewed 76 jury eligible, death qualified citizens and asked them to imagine a first-degree murder scenario, describing the events that led to the killing. We coded the presence of dichotomous variables in the resulting stories and identified at least three shared story prototypes using cluster and profile analysis. We conclude that people do not store crime stories as simple prototypes and comment on the implications of this finding for legal decision-making.

Adult↗

PubMed2003

Neuronal expression of tachykinin-related peptides and gene transcript during postembryonic development of Drosophila.

The gene Dtk, encoding the prohormone of tachykinin-related peptides (TRPs), has been identified from Drosophila. This gene encodes five putative tachykinin-related peptides (DTK-1 to 5) that share the C-terminal sequence FXGXRamide (where X represents variable residues) as well as an extended peptide (DTK-6) with the C-terminus FVAVRamide). By mass spectrometry (MALDI-TOF-MS), we identified ion signals with masses identical to those of DTK-1 to 5 in specific brain regions. We have analyzed the distribution of the Dtk transcript and peptides, by in situ hybridization and immunocytochemistry during postembryonic development of the central nervous system (CNS) of Drosophila. Antiserum against a cockroach TRP that cross-reacts with the DTKs was used for immunocytochemistry. Expression of transcript and peptides was detected from first to third instar larvae, through metamorphosis to adult flies. Throughout postembryonic development, we were able to follow the strong expression of TRPs in a pair of large descending neurons with cell bodies in the brain. The number of TRP-expressing neuronal cell bodies in the brain and ventral nerve cord increases during larval development. In the early pupa (stage P8), the number of TRP-expressing cell bodies is lower than in the third instar larvae. The number drastically increases during later pupal development, and in the adult fly about 200 TRP-expressing neurons can be seen in the CNS. The continuous expression of TRPs in neurons throughout postembryonic development suggests specific functional roles in both larval and imaginal flies and possibly also in some neurons during pupal development.

Animals↗

PubMed2005

Personality and anorexia nervosa.

We provided a selective review of the relationship between anorexia nervosa (AN) and personality. They reviewed the existing empirical literature examining the relationship between AN and personality. In spite of continued methodologic challenges related to personality assessment, there appears to be a relatively common phenotype in restricting-type AN characterized by high degrees of obsessionality, restraint, and perfectionism. However, there is also evidence of variability within the AN diagnostic category that is related to personality variables. Importantly, personality variables may significantly predict the course and outcome of AN. Personality variables may be risk factors for AN, consequences of AN, share a common cause with AN, or affect the course and outcome of AN. This literature would be enhanced by the articulation of conceptual models of these relationships that can be empirically tested.

Anorexia Nervosa↗

PubMed2003

Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1.

The two known complementation groups of Niemann-Pick Type C disease, NPC1 and NPC2, result from non-allelic protein defects. Both the NPC1 and NPC2 (HE1) gene products are intimately involved in cholesterol and glycolipid trafficking and/or transport. We describe mutation analysis on samples from 143 unrelated affected NPC patients using conformation sensitive gel electrophoresis and DNA sequencing as the primary mutation screening methods for NPC1 and NPC2, respectively. These methods are robust, sensitive, and do not require any specialized laboratory equipment. Analyses identified two NPC1 mutations for 115 (80.4%) patients, one NPC1 mutation for 10 (7.0%) patients, two NPC2 mutations for five (3.5%) patients, one NPC2 mutation for one (0.7%) patient, and no mutations for 12 (8.4%) patients. Thus, mutations were identified on 251 of 286 (88%) disease alleles, including 121 different mutations (114 in NPC1 and seven in NPC2), 58 of which are previously unreported. The most common NPC1 mutation, I1061T, was detected on 18% of NPC alleles. Other NPC1 mutations were mostly private, missense mutations located throughout the gene with clustering in the cysteine-rich luminal domain. Correlation with biochemical data suggests classification of several mutations as severe and others as moderate or variable. The region between amino acids 1038 and 1253, which shares 35% identity with Patched 1, appears to be a hot spot for mutations. Additionally, a high percentage of mutations were located at amino acids identical to the NPC1 homolog, NPC1L1. Biochemical complementation analysis of cases negative for mutations revealed a high percentage of equivocal results where the complementation group appeared to be non-NPC1 and non-NPC2. This raises the possibilities of an additional NPC complementation group(s) or non-specificity of the biochemical testing for NPC. These caveats must be considered when offering mutation testing as a clinical service.

Base Sequence↗

PubMed2005

Development of crop-specific transposable element (SINE) markers for studying gene flow from oilseed rape to wild radish.

The screening of wild populations for evidence of gene flow from a crop to a wild related species requires the unambiguous detection of crop genes within the genome of the wild species, taking into account the intraspecific variability of each species. If the crop and wild relatives share a common ancestor, as is the case for the Brassica crops and their wild relatives (subtribe Brassiceae), the species-specific markers needed to make this unambiguous detection are difficult to identify. In the model oilseed rape (Brassica napus, AACC, 2n = 38)-wild radish (Raphanus raphanistrum, RrRr, 2n = 18) system, we utilized the presence or absence of a short-interspersed element (SINE) at a given locus to develop oilseed rape-specific markers, as SINE insertions are irreversible. By means of sequence-specific amplified polymorphism (SINE-SSAP) reactions, we identified and cloned 67 bands specific to the oilseed rape genome and absent from that of wild radish. Forty-seven PCR-specific markers were developed from three combinations of primers anchored either in (1) the 5'- and 3'-genomic sequences flanking the SINE, (2) the 5'-flanking and SINE internal sequences or (3) the SINE internal and flanking 3'-sequences. Seventeen markers were monomorphic whatever the oilseed rape varieties tested, whereas 30 revealed polymorphism and behaved either as dominant (17) or co-dominant (13) markers. Polymorphic markers were mapped on 19 genomic regions assigned to ten linkage groups. The markers developed will be efficient tools to trace the occurrence and frequency of introgressions of oilseed rape genomic region within wild radish populations.

Brassica napus↗

PubMed2005

Prion disease with a 144 base pair insertion: unusual cerebellar prion protein immunoreactivity.

Sporadic, acquired, and genetic human prion diseases are characterized neuropathologically by distinct deposition patterns of the abnormal, disease-associated form of the prion protein (PrP(sc)). In addition to mutations in the prion protein gene (PRNP), PrP(sc) immunostaining patterns correlate with molecular phenotypes of prion diseases defined by the PRNP polymorphism at codon 129 and with protease-resistant PrP classified by Western blotting. Some point or insertional PRNP mutations share similar clinical and neuropathological phenotypes, whereas others show great variability even within the same family. Here we report a patient who presented clinically as sporadic Creutzfeldt-Jakob disease (CJD). Histologically moderate spongiform change was seen in cerebral and cerebellar cortical areas. Neuronal loss was restricted mainly to the occipital cortex and the basal ganglia. Surprisingly, numerous eosinophilic globular structures were noted in the molecular layer and the parahippocampal gyrus. These globules showed intense PrP immunopositivity using anti-PrP antibodies against different epitopes. They were stained with PAS but lacked congophilia and birefringence in polarized light. Ultrastructurally, globules were composed of 21-nm-thick intermingled filaments without dense core. Genetic analysis revealed a PRNP 144 base pair insertion. Our case reinforces the importance of molecular genetic diagnosis, especially in those patients who lack a family history of prion disease and show unusual neuropathological changes. It also widens the phenotypic spectrum of prion diseases. The phenotypic variability within the same mutation suggests further, yet uncharacterized, genetic or epigenetic influence on phenotype in these diseases.

Aged↗

PubMed1983

An evaluation of space-time clustering in Hodgkin's disease.

A survey in Greater Boston identified 1577 new cases of histologically-confirmed Hodgkin's disease (HD) diagnosed from 1959 to 1973. The spatial position of each case was taken as the place of residence at diagnosis, and the temporal position as the month and year of diagnosis. Sufficient data for analysis were available for 1398 cases (89%). Space-time clustering was evaluated by three different methods: (a) Knox, (b) David and Barton and (c) Ederer, Myers and Mantel. When all HD cases were considered, none of these methods revealed statistically significant clustering. When stratification by risk factors was done, each of the techniques found significant clustering for various subgroups. Young adult cases (age 16-45 yr) tended to cluster more than older cases (age 46-70) and Catholics more than Jewish or Protestant cases. Rather than suggesting clustering at the time of HD diagnosis, the sporadic and inconsistently positive findings of this study may reflect case aggregation at the time of shared etiologic exposures, particularly if HD has a long and/or variable latent period.

Adolescent↗

PubMed1984

Situational moderators of leader reward and punishment behaviors: fact or fiction?

One assumption shared by many contemporary models of leadership is that situational variables moderate the relationships between leader behaviors and subordinate responses. Recently, however, R. J. House and J. L. Baetz (1979 in B. Staw & L. Cummings, Eds., Research in Organizational Behavior (Vol. 1), Greenwich, Connecticut, JAI Press) have suggested that the effects of some leader traits and behaviors may be relatively invariant; that is, have the same effects in a variety of situations. One possible class of leader behaviors which may have relatively consistent effects across situations are those known as leader reward and punishment behaviors. The first goal of the research reported here was to increase our understanding of the relationships between leader contingent and noncontingent reward and punishment behaviors and subordinate responses. Contingent reward behavior was found to have the most pronounced relationships with subordinate performance and satisfaction, followed by noncontingent punishment behavior. Neither leader noncontingent reward nor contingent punishment behavior were found to be related to either subordinate performance or satisfaction, with the exception that noncontingent reward behavior was negatively related to subordinates' satisfaction with work. The second goal of the research was to examine the effects of a variety of potential moderators on the relationships between leader reward and punishment behaviors and subordinate responses. The results of this study suggest that the relationships between leader reward and punishment behaviors and subordinates' performance are relatively free of moderating effects.

Factor Analysis, Statistical↗

PubMed1990

Rapid and sensitive sequence comparison with FASTP and FASTA.

The FASTA program can search the NBRF protein sequence library (2.5 million residues) in less than 20 min on an IBM-PC microcomputer and unambiguously detect proteins that shared a common ancestor billions of years in the past. FASTA is both fast and selective because it initially considers only amino acid identities. Its sensitivity is increased not only by using the PAM250 matrix to score and rescore regions with large numbers of identities but also by joining initial regions. The results of searches with FASTA compare favorably with results using NWS-based programs that are 100 times slower. FASTA is slightly less sensitive but considerably more selective. It is not clear that NWS-based programs would be more successful in finding distantly related members of the G-protein-coupled receptor family. The joining step by FASTA to calculate the initn score is especially useful for sequences that share regions of sequence similarity that are separated by variable-length loops. FASTP and FASTA were designed to identify protein sequences that have descended from a common ancestor, and they have proved very useful for this task. In many cases, a FASTA sequence search will result in a list of high scoring library sequences that are homologous to the query sequence, or the search will result in a list of sequences with similarity scores that cannot be distinguished from the bulk of the library. In either case, the question of whether there are sequences in the library that are clearly related to the query sequence has been answered unambiguously. Unfortunately, the results often will not be so clear-cut, and careful analysis of similarity scores, statistical significance, the actual aligned residues, and the biological context are required. In the course of analyzing the G-protein-coupled receptor family, several proteins were found that, because of a high initn score and a low init1 score that increased almost 2-fold with optimization, appeared to be members of this family which were not previously recognized. RDF2 analysis showed borderline z values, and only a careful examination of the sequence alignments that focused on the conserved residues provided convincing evidence that the high scores were fortuitous. As sequence comparison methods become more powerful by becoming more sensitive, they become more likely to mislead, and even greater care is required.

Algorithms↗

PubMed1986

Diversity of cell surface hematopoietic antigens on K-562 sublines identified with monoclonal antibodies.

The surface antigen profile of 8 sublines of K-562 cells, the original line, and the clone RA6 was determined with a panel of 12 monoclonal antibodies reactive with hematopoietic cell differentiation antigens. Cells from all sublines expressed the precursor hematopoietic antigen reactive with RFB-1, the T-cell antigen reactive with OKT17, the B cell/granulocyte antigen reactive with BA-1, the My-1 antigen, and glycophorin A which reacted with R10. A low percentage of cells in some of the sublines expressed platelet/monocyte glycoprotein I binding AN51, monocyte antigen binding 63D3, and an erythroblast/monocyte/platelet antigen binding 5F1. The use of a panel of K-562 sublines demonstrates that K-562 cells do share several "common" antigens but express a marked diversity and variability of other hematopoietic antigens.

Antibodies, Monoclonal↗

PubMed1991

What healthy women think, feel and do about cancer, prevention and breast cancer screening in Italy.

In preparation for a major campaign to encourage participation in a breast screening programme for all women between 50-70 years old in Florence, Italy, an in-depth study of 200 women's attitudes and practices regarding cancer and its prevention was undertaken. 72% participated in semistructured interviews, and inclination to participate was analysed in terms of Yes (39%), Uncertain (36%), and No (20%) (5% were unspecified). Age (P = 0.03), area of birth (P = 0.01), education level of husband (P = 0.04) and prior Pap smear (P = 0.00) or mammography (P = 0.00) were among the variables statistically associated with inclination to participate. While the women shared more or less common images of cancer, concern for health, and belief in the importance of God and destiny, those less inclined to participate felt less personally vulnerable, had less faith in medicine's ability to cure or prevent cancer, were more distant from the medical system and culture in general and regarded information about health or illness more as unnecessary or dangerous than beneficial. Understanding and consideration of both "popular" and "medical" cultures need to be encouraged.

Aged↗

PubMed2005

How the T cell repertoire becomes peptide and MHC specific.

T cells bearing alphabeta T cell receptors (TCRs) recognize antigens in the form of peptides bound to class I or class II major histocompatibility proteins (MHC). TCRs on mature T cells are usually very specific for both peptide and MHC class and allele. They are picked out from a precursor population in the thymus by MHC-driven positive and negative selection. Here we show that the pool of T cells initially positively selected in the thymus contains many T cells that are very crossreactive for peptide and MHC and that subsequent negative selection establishes the MHC-restriction and peptide specificity of peripheral T cells. Our results also suggest that germline-encoded TCR variable elements have an inherent predisposition to react with features shared by all MHC proteins.

Alleles↗

PubMed2006

Private specificities of heterologous immunity.

Antiviral T-cell responses between individuals that have similar major histocompatibility complex molecules share similarities in epitope hierarchies and T-cell receptor variable gene usage (public specificities), yet the T-cell receptor amino acid sequences differ between individuals (private specificities). The significance of the private specificities of these repertoires is brought about under conditions of heterologous immunity and might have important consequences in anti-viral immunity and immunopathology.

Animals↗

PubMed2005

Molecules and morphology: evidence for introgression of mitochondrial DNA in Dalmatian cyprinids.

In one population of Scardinius dergle, mitochondrial DNA was observed originating from Squalius tenellus. Scardinius dergle shared all diagnostic morphological characters and similarities at a highly variable nuclear region with the genus Scardinius. While crosses and backcrosses most likely resulted in the loss of morphologically diagnostic Squalius-features, maternal inheritance of mtDNA fixed their diagnostic substitutions. Anthropogenic influences resulting from dam building in 1962 are suspected to be the initial force for the hybridization events. However, because hybridization took place despite both lineages being only very distantly related (p=11.2%), we conclude that introgressive hybridization events can be seen as generally possible among leuciscine cyprinids.

Animals↗

PubMed1998

Sibling pairs with schizophrenia or schizoaffective disorder: associations of subtypes, symptoms and demographic variables.

BACKGROUND: Affected sibling pairs provide a valuable means of investigating the familial basis of clinical heterogeneity in schizophrenia. METHODS: Associations of schizophrenia subtypes, psychotic symptoms (defined by SAPS/SANS and OPCRIT), affective episodes and demographic variables were studied in 109 sibling pairs with DSM-IV schizophrenia or schizoaffective disorder. RESULTS: None of the subtypes or affective episodes were significantly associated within pairs. A broad definition of positive formal thought disorder, grandiose delusions and delusions of influence (all from OPCRIT) were modestly associated. There was no excess of same-sex pairs. There were modest associations for age of illness onset, pre-morbid adjustment and illness severity. Caution is required in interpreting the results because many statistical tests were carried out. CONCLUSIONS: None of the variables appears to be closely associated with specific genetic or shared environmental factors that contribute liability to schizophrenia. They are at best only weakly associated with such factors, and/or are associated with factors unrelated to the aetiology of schizophrenia.

Adult↗