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An outbreak of salmonellosis among children attending a reptile exhibit at a zoo.

OBJECTIVE: In January 1996, an outbreak of diarrhea caused by Salmonella Enteritidis occurred in children attending a Komodo dragon exhibit at a metropolitan zoo. We sought to determine the extent of the outbreak and mode of transmission. STUDY DESIGN: A case-control study was conducted. Controls were randomly selected from zoo membership lists and matched to patients by age group and date of exhibit visit. RESULTS: Of 65 patients identified, 39 had confirmed and 26 had suspected cases. The median age was 7 years (range, 3 months to 48 years); 55% were enrolled in the case-control study. No patients and two (4%) controls reported touching a dragon; however, 83% of patients but only 52% of controls touched the wooden barrier that surrounded the dragon pen (odds ratio = 4.0, 95% CI 1.2 to 13.9). Washing hands at the zoo after visiting the dragons was highly protective (OR = 0.14, 95% CI 0.03 to 0.7). Cultures from the patients, one dragon, and the exhibit barriers yielded Salmonella Enteritidis, phage type 8. On the basis of an attack rate of 4.3% among exhibit attendees under 13 years old on whom data were collected, we estimate that 315 additional cases of salmonellosis occurred among visitors in this age group. CONCLUSION: This large outbreak demonstrates the importance of environmental contamination in the transmission of Salmonella from reptiles, and the protective value of hand washing. Recommendations regarding reptile exhibits and reptilian pets should emphasize this indirect route.

Adolescent↗

Isomers of human alpha-synuclein stabilized by disulfide bonds exhibit distinct structural and aggregative properties.

The discovery of three mutants in the -synuclein (alphaSyn) gene and the identification of alphaSyn as the major component of Lewy body have opened a new field for understanding the pathogenesis of Parkinson's disease (PD). AlphaSyn is a natively unfolded protein with unknown function and unspecified conformational heterogeneity. In this study, we introduce four Ser/Ala --> Cys mutations at positions 9, 42, 69, and 89 in human wild-type alphaSyn (wt-alphaSyn) and two PD-associated alphaSyn mutants, A30P-alphaSyn and A53T-alphaSyn. This allows expression of three alphaSyn mutants, wt-alphaSyn(4C), A30P-alphaSyn(4C), and A53T-Syn(4C). Subsequent oxidative folding enables each alphaSyn(4C) mutant to form three partially stabilized two-disulfide isomers, designated as alphaSyn(2SS), that are amenable to further isolation and characterization. These alphaSyn mutants exhibit the following properties. (a) A30P-alphaSyn(4C) exhibits a lower folding flexibility than wt-alphaSyn(4C) and A53T-alphaSyn(4C). (b) All three alphaSyn(4C) mutants, like wt-alphaSyn, exhibit a predominant structure of random coil. However, wt-alphaSyn(2SS) adopts an alpha-helical conformation, whereas A30P-alphaSyn(2SS) and A53T-alphaSyn(2SS) take on significant beta-sheet structure. (c) A30P-alphaSyn(2SS) shows a stronger tendency to aggregate than A53T-alphaSyn(2SS) and wt-alphaSyn(2SS). (d) Three isolated isomers of wt-alphaSyn(2SS) exhibit a propensity for forming oligomers different yet enhanced versus that for wt-alphaSyn. These data together substantiate the notion that under physiological conditions, human alphaSyn exists as diverse conformational isomers which exhibit distinct propensities for aggregation and fibril formation.

Amino Acid Sequence↗

The rat leukocyte-type 12-lipoxygenase exhibits an intrinsic hepoxilin A3 synthase activity.

Hepoxilins are biologically relevant eicosanoids formed via the 12-lipoxygenase pathway of the arachidonic acid cascade. Although these eicosanoids exhibit a myriad of biological activities, their biosynthetic mechanism has not been investigated in detail. We examined the arachidonic acid metabolism of RINm5F rat insulinoma cells and found that they constitutively express a leukocyte-type 12S-lipoxygenase. Moreover, we observed that RINm5F cells exhibit an active hepoxilin A(3) synthase that converts exogenous 12S-HpETE (12S-5Z,8-Z,10E,14Z-12-hydro(pero)xy-eicosa-5,8,10,14-tetraenoic acid) or arachidonic acid predominantly to hepoxilin A(3). 12S-lipoxygenase and hepoxilin A(3) synthase activities were co-localized in the cytosol; immunoprecipitation with an anti-12S-lipoxygenase antibody co-precipitated the two catalytic activities. These data suggested that hepoxilin A(3) synthase activity may be considered an intrinsic catalytic property of the leukocyte-type 12S-lipoxygenase. To test this hypothesis we cloned the leukocyte-type 12S-LOX from RINm5F cells, expressed it in Pichia pastoris, and found that the recombinant enzyme exhibited both 12S-lipoxygenase and hepoxilin A(3) synthase activities. The recombinant human platelet-type 12S-lipoxygenase and the porcine leukocyte-type 12S-lipoxygenase also exhibited hepoxilin A(3) synthase activity. In contrast, the native rabbit reticulocyte-type 15S-lipoxygenase did not convert 12S-HpETE to hepoxilin isomers. These data suggest that the positional specificity of lipoxygenases may be crucial for this catalytic function. This hypothesis was confirmed by site-directed mutagenesis studies that altered the positional specificity of the rat leukocyte-type 12S- and the rabbit reticulocyte-type 15-lipoxygenase. In summary, it may be concluded that naturally occurring 12S-lipoxygenases exhibit an intrinsic hepoxilin A(3) synthase activity that is minimal in lipoxygenase isoforms with different positional specificity.

Amino Acid Sequence↗

Functional analysis of mononuclear cells infiltrating into tumors: establishment of T cell hybridomas exhibiting distinct interacting abilities with endothelial cells and extracellular matrix components.

We have established eleven T cell hybridoma cell lines to investigate mechanisms controlling interaction of T lymphocytes with endothelial cells as well as extracellular matrix (ECM) proteins at the clonal level. T cell hybridomas were characterized and subdivided into four groups on the basis of their interaction behavior with high endothelial venules (HEV). Group 1 (G1) exhibited strong adhesiveness. The binding was temperature- and divalent cation-dependent. Group 2 exhibited both adhesiveness and transendothelial migration (TEM, i.e., transmigration beneath the cytoplasm of endothelial cells). Group 3 exhibited strong TEM. G2 and G3 hybridomas exhibited temperature-independent and divalent cation-independent binding to HEV. Group 4 exhibited nonspecific adhesiveness to the surface of a slide glass. BW 5147, a parent of T cell hybridomas, was classified as G4. TEM was dependent on both the nature of T cell hybridomas and endothelial cells. TEM was completely temperature-dependent. TEM of G3 hybridomas was not divalent cation-dependent. Each group of T cell hybridomas interacted with various ECM components.

Amino Acid Sequence↗

Recombinant human pim-1 protein exhibits serine/threonine kinase activity.

The protein predicted by the sequence of the human pim-1 proto-oncogene shares extensive homology with known serine/threonine protein kinases, and yet the human Pim-1 enzyme has previously been reported to exhibit protein tyrosine kinase activity both in vitro and in vivo. Recently a new class of protein kinases has been identified which exhibits both protein-serine/threonine and protein-tyrosine kinase activities. We therefore investigated the possibility that the human Pim-1 kinase likewise possesses such bifunctional enzymatic phosphorylating activities. A full-length human pim-1 cDNA was subcloned into the bacterial vector pGEX-2T and the Pim-1 protein expressed as a fusion product with bacterial glutathione S-transferase (GST). The hybrid GST-Pim-1 fusion protein was affinity purified on a glutathione-Sepharose column prior to treatment with thrombin for cleavage of the Pim-1 protein from the transferase. Pim-1 was purified and the identity of recombinant protein confirmed by amino-terminal sequence analysis. Pim-1 was tested for kinase activity with a variety of proteins and peptides known to be substrates for either mammalian protein-serine/threonine or protein-tyrosine kinases and was found to phosphorylate serine/threonine residues exclusively in vitro. Both the Pim-1-GST fusion protein and the isolated Pim-1 protein exhibited only serine/threonine phosphorylating activity under all in vitro conditions tested. Pim-1 phosphorylated purified mammalian histone H1 with a Km of approximately 51 microM. Additionally, Pim-1 exhibited low levels of serine/threonine autophosphorylating activity. These observations place the human Pim-1 in a small select group of cytoplasmic transforming oncogenic kinases, including the protein kinase C, the Raf/Mil, and the Mos subfamilies, exhibiting serine/threonine phosphorylating activity.

Cloning, Molecular↗

Exhibiting mentally retarded people for amusement and profit, 1850-1940.

Historians in the field of mental retardation have neglected to document the exhibition of people for amusement and profit, commonly known as "freak shows." The exhibition of people we would now call "mentally retarded" during the period 1850 to 1940 in the United States was discussed. Biographical sketches were given to five famous persons who were exhibited in the 19th century. Information on other individuals who were exhibited was also provided. Patterns and trends in exhibitions and in the significance of "freak show" imagery for current attitudes toward those known as mentally retarded was discussed.

History, 19th Century↗

Adam Politzer, otology and the Centennial Exhibition of 1876.

The Centennial Exhibition of 1876 was held in Philadelphia. Among the exhibits was a collection of temporal bone dissections produced by Adam Politzer of Vienna. This exhibit included both normal and pathological temporal bones, and emphasized the relationship of the tympanic membrane to the middle ear, external canal and bony labyrinth. At the close of the Centennial Exhibition the collection was purchased by the College of Physicians of Philadelphia. This collection and the congress associated with the Centennial had a tangible effect on the otology in this country.

Ear Canal↗

[Medicine in concentration camps: deliberate neglect, minimal care, medical crimes. A permanent exhibition at the memorial site of Sachsenhausen].

In November 2004, the exhibition "Medicine and Crime" was opened at the Memorial Site of Sachsenhausen near Berlin. The exhibition is located in barracks R I and R II, which have persisted in their original form. These barracks were part of the camp infirmary, which was extended repeatedly up to the end of the war. Its medical facilities included laboratories, operating theatres and wards. The infirmary was the place where "racial research" and numerous medical experiments were carried out on inmates. SS doctors performed compulsory sterilisations and castrations. Several thousand inmates were murdered in systematically planned programmes to dispose of the sick, such as "Operation 14f 13". As shown in the exhibition, the infirmary was also meant for providing minimal medical care for inmates to prevent the spread of contagious diseases and epidemics. In 1942, after setbacks in the war, attention was paid to restoring sick inmates' ability to work. Overcrowding, inhuman treatment and poor supply of medicines led to largely disastrous conditions in the infirmary. It is a special aspect of this exhibition that the events in the infirmary are told from the perspective of the inmates, i. e. the victims, not the perpetrators.

Concentration Camps↗

Exhibits in health sciences libraries.

The exhibit policies and practices of health sciences libraries have been surveyed. This paper discusses the administration of exhibits, preservation of exhibited materials, and special practices and techniques used in developing and installing exhibits. Recommendations for safe display of materials are made.

Costs and Cost Analysis↗

150 years of the New York Academy of Medicine: a series of exhibitions.

As the New York Academy of Medicine celebrates its 150th year as a leader in the field of urban health, it is instructive to review the events and decisions that influenced and shaped it. Since its inception, the Academy has taken an active role in lobbying state and local governments to enact more-effective public health laws and in educating the public about improving health conditions. During 1996 and 1997, the Academy Library's Historical Collections is mounting a series of six exhibitions that are intended to tell the story of public health in New York as influenced by the New York Academy of Medicine. The story will be told using printed books, pamphlets, posters, photographs, and manuscripts drawn from the Library's collections, as well as the Academy's archives. Each exhibition will highlight the Academy's accomplishments in the subject areas presented. In this article, we summarize all six of the exhibitions and offer an in-depth look at the first two exhibitions.

Disease Outbreaks↗

A cryptic Bacillus isolate exhibited narrow 16S rRNA gene sequence divergence with Bacillus thuringiensis and showed low maintenance requirements in hyper-osmotic complex substrate cultivations.

A cryptic Bacillus (K90) isolate obtained from soil samples from the Kuwait desert exhibited lower maintenance requirements in complex substrate cultivations than Bacillus thuringiensis. A mathematical model was used to estimate apparent maintenance coefficients (m(c)) and these were found to be 0.336 and 0.041/h for B. thuringiensis and K90, respectively. The results also showed that the values of apparent maintenance coefficients were inversely related to the specific growth rates. Furthermore, 16S rRNA gene sequencing showed that K90 exhibited 99.81% sequence similarity to that of B. mojavensis and 92.9% with B. thuringiensis. It is evident from the dendrogram that the evolution of B. mojavensis (K90) (B. subtilis group), which may have originated after B. licheniformis could have been influenced by prolonged hyper-osmotic conditions, while B. thuringiensis that evolved before B. oleronius exhibited greater sensitivity as implied by the higher maintenance coefficient obtained for the hyper-osmotic cultures. As K90 exhibited low maintenance requirements in hyperosmotic cultures, close phylogenetic relationship with B. thuringiensis, along with the reported property of encapsulation of insecticidal crystal proteins (Cry) in Bacillus strains and endophytic nature of B. mojavensis, strongly suggest that K90 could be a promising surrogate host for the transgenic delivery of "Cry" proteins.

Bacillus↗

Drosophila purine auxotrophy: new alleles of adenosine 2 exhibiting a complex visible phenotype.

New mutant alleles of the adenosine2 locus (ade2; 2-17.7) have been isolated using the eye-color phenotype exhibited by the prototype auxotrophic allele ade2 as the screening criterion. The new mutants form a single complementation group, suggesting that they all exhibit purine auxotrophy and defective formylglycineamide ribotide amidotransferase enzyme, like ade2. Tests carried out on particular new alleles confirm these suggestions. The new mutants all exhibit more extreme physical defects than the prototype. They have wing abnormalities like mutants defective in pyrmidine biosynthesis and reduced bristles like those defective in protein synthesis; thus they exhibit the combined visible phenotype of rudimentary wings, rosy eyes, and bobbed bristles. Cytogenetic analysis places the locus in the interband proximal to 26B1-2.

Adenosine↗

PC12 cells grown on cellulosic filters differentiate in response to NGF and exhibit a polarity not seen when they are grown on solid substrata.

Studies were performed with cellulosic filters and standard culture plates to compare methods of cell culture and differentiation of the cell line PC12, a clone originating from a rat pheochromocytoma. PC12 cells respond to nerve growth factor (NGF) by flattening of the cell body and subsequent extension of neurite-like processes. When PC12 cells are cultured in dishes without NGF, they have a diameter of approximately 3 to 7 micron and exhibit short processes of no longer than 3 to 5 micron. If PC12 cells are grown on a cellulosic filter they have the same average soma diameter and similar short processes extending laterally, but in addition have branching processes which extend as far as 10 to 15 micron into the filter substrate. When dish-cultured and filter-cultured cells are incubated with 50 ng/ml NGF they both exhibit differentiation-specific ultrastructural changes by 3 d of treatment. In the case of dish-cultured cells, large cytoplasmic processes exhibit an increase in the number of chromaffin cell-like secretory granules by 3 d of treatment. This characteristic is also demonstrated by filter-cultured cells, but the processes containing these granules are found concentrated within the cellulosic meshwork. Thus the timing of the NGF-elicited differentiation program is similar to both filter-cultured and dish-cultured cells, but the ultrastructural consequences are different. The filter-cultured PC12 cells exhibit a polarity not demonstrated by dish-cultured cells. Growing PC12 cells on cellulosic filters is a technique useful for "anchoring" neurons without the complication of the addition of extracellular matrix components. Filter-culture may represent a more in vivo-like method for studying neuronal growth and differentiation.

Adrenal Gland Neoplasms↗

Teleost fish genomes contain a diverse array of L1 retrotransposon lineages that exhibit a low copy number and high rate of turnover.

Retrotransposable elements exhibit a wide range of variation in population dynamics, abundance, and lineage diversity among host genomes across taxa. This range of diversity is illustrated by a single well-defined constituent monophyletic clade of L1 non-LTR retrotransposons that is shared between mammalian and teleost fish genomes. Despite the clear phylogenetic relationships that exist between mammalian and teleost L1 sequences, these elements exhibit markedly different dynamics within their respective taxa. While mammalian genomes typically contain a single, abundant lineage of L1 elements that traces millions of years of evolution, the zebraflsh genome was recently shown to exhibit a high diversity of ancient lineages coexisting at a very low copy number and apparently exhibiting a high rate of turnover. In the present study, a combination of degenerate PCR, lineage-specific PCR, and genomic Southern blot analysis is utilized to demonstrate high L1 lineage diversity, low copy number, and a high proportion of polymorphic inserts in the genomes of the killifish species, Fundulus heteroclitus. Additional species surveyed by degenerate PCR include Cyprinodon variegatus, Rivulus marmoratus, and Menidia beryllina. These results further support the generality of the differences that exist in host-element dynamics between teleost fish and mammalian genomes with regard to L1 retrotransposons.

Animals↗

Flinders resistant hypocholinergic rats exhibit startle sensitization and reduced startle thresholds.

Based on the hypothesis that depression involves a cholinergic-adrenergic neurotransmitter imbalance, a putative genetic animal model of depression has been developed by selectively breeding rats to exhibit hypocholinergia (Flinders Resistant Line--FRL), or hypercholinergia (Flinders Sensitive Line--FSL). The present experiments were designed to test the behavioral reactivity of these rats to external stimuli by measuring acoustic startle responses. The FRL rats exhibited lower startle thresholds compared to both FSL and control rats, while the FSL rats' startle thresholds were between those of controls and FRL rats. Despite the differences in thresholds, the three groups demonstrated similar levels of maximal startle reactivity to a high-intensity acoustic stimulus. With repeated stimulus presentations, FRL rats developed startle sensitization, a rarely observed phenomenon, while FSL and control rats exhibited habituation. There were no differences between the three groups in prepulse inhibition of startle. These results indicated that FRL rats exhibited interesting startle phenomena that are characteristic of certain psychiatric disorders, such as schizophrenia, post-traumatic stress disorder, and, potentially, depression.

Acetylcholine↗

Mice exposed in utero to 20 ppm benzene exhibit altered numbers of recognizable hematopoietic cells up to seven weeks after exposure.

Pregnant Swiss Webster mice were exposed from Day 6 through Day 15 of gestation to either air, 5 ppm, 10 ppm, or 20 ppm benzene. On Day 16 of gestation, 2 days after birth, and 6 weeks after birth, progeny of the exposed dams were assayed for the amount and type of hemoglobin produced and for recognizable hematopoietic cells in the peripheral blood and hematopoietic organs. None of the benzene exposures induced significant changes in the indices assayed from the 16-day fetuses. In contrast, 2-day neonates exposed in utero to all concentrations of benzene exhibited reduced numbers of circulating erythroid percursor cells. In addition, those 2-day neonates exposed in utero to 20 ppm benzene exhibited increased numbers of hepatic hematopoietic blast cells and granulopoietic precursor cells accompanied by decreased numbers of erythropoietic precursor cells. Six-week adult mice exposed in utero to 20 ppm benzene exhibited a similar pattern of enhanced granulopoiesis. These animals exhibited elevated numbers of splenic hematopoietic blast cells and granulopoietic precursor cells accompanied by decreased numbers of marrow erythropoietic precursor cells. These results suggest that in utero exposures to low concentrations of benzene can induce persistent enhanced production of recognizable granulopoietic elements in the hematopoietic systems of mice.

Animals↗

Pyramidal neurons with ectopic dendrites in storage diseases exhibit increased GM2 ganglioside immunoreactivity.

Cortical pyramidal neurons in several types of neuronal storage diseases have been shown by Golgi staining to sprout axon hillock-associated dendritic processes. Based on the relative incidence of this ectopic dendritogenesis, and on quantitative analyses of gangliosides in these same tissues, it has been proposed that abnormal accumulation of a specific metabolic product, GM2 ganglioside, is the pivotal event leading to re-initiation of dendritic sprouting [Siegel D. A. Walkley S.U. (1994) J. Neurochem. 62, 1852-1862]. In the present study, a monoclonal antibody was used to determine the cellular location of this ganglioside within the cerebral cortex of animal models of storage diseases with and without ectopic dendrite growth. Diseases exhibiting ectopic dendritogenesis included inherited and swainsonine-induced (juvenile-onset) alpha-mannosidosis, mucopolysaccharidosis type I, Niemann-Pick disease type C, and GM1 and GM2 gangliosidosis. Conditions lacking ectopic dendrite growth included adult-onset swainsonine-induced alpha-mannosidosis, fucosidosis, neuronal ceroid lipofuscinosis (Batten disease) and normal, mature brain. Immunocytochemical staining for GM2 ganglioside indicated that diseases exhibiting new dendritic sprouting with the exception of GM1 gangliosidosis, exhibited abundant GM2-like immunoreactivity within the cortical pyramidal cell population, whereas diseases without dendritic sprouting had GM2-like immunoreactivity limited to glia and/or to non-pyramidal neurons. Cortical tissues from normal animals at comparable ages and processed by similar procedures exhibited occasional glial cell staining but little or no neuronal labelling. Mechanisms by which normal cortical pyramidal regulate dendritic initiation are poorly understood. However, it is known that this event is developmentally restricted, occurring only during early brain development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Male NOD mouse external lacrimal glands exhibit profound changes in the exocytotic pathway early in postnatal development.

The lacrimal glands of male NOD mice exhibit many of the features of the human lacrimal gland in patients afflicted with the autoimmune disease, Sjögren's syndrome, including loss of secretory functions and lymphocytic infiltration into the lacrimal gland. To elucidate the early changes in the secretory pathway associated with development of Sjögren's syndrome, we investigated the organization of the exocytotic pathway in lacrimal glands of age-matched male BALB/c and NOD mice. Cryosections from lacrimal glands from 1 and 4 month male BALB/c and NOD mice were processed for confocal fluorescence and electron microscopic evaluation of different participants in exocytosis. No changes in apical actin filaments were noted in glands from NOD mice, but these glands exhibited thickening of basolateral actin relative to that seen in the BALB/c mice. Rab3D immunofluorescence associated with mature secretory vesicles was distributed abundantly in a continuous vesicular network concentrated beneath the apical plasma membrane in glands from 1 and 4 month BALB/c mice. In glands from 1 month NOD mice, rab3D immunofluorescence exhibited marked discontinuity and irregularity in the vesicular labeling pattern. While this change was also detected in glands from 4 month NOD mice, many of these glands exhibited an additional extension of rab3D labeling through the cell to the basolateral membrane. Electron microscopic analysis confirmed the formation of irregularly shaped, unusually large secretory vesicles in lacrimal glands from NOD mice. Quantitation of multiple secretory vesicles from electron micrographs revealed a significant (p< or =0.05) increase in the percentage of secretory vesicles incorporated into multivesicular aggregates in lacrimal glands from 1 and 4 month NOD mice compared to BALB/c mice. The M3 muscarinic receptor, a key signaling effector of exocytosis, was redistributed away from its normally basolateral locale in glands from BALB/c mice, with concomitant enrichment in intracellular aggregates in glands from NOD mice. These findings show that lacrimal glands in NOD mice as young as 1 month contain aberrant secretory vesicles with altered effector composition that undergo premature cytoplasmic fusion, and that changes in the distribution of the M3 muscarinic receptor occur within the same time frame.

Animals↗