bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Aspects of CAG Repeat Diseases
Authors: Nance Martha A. 
Published: January 2008

Seven neurodegenerative disorders are known to be caused by unstable expansions of the trinucleotide CAG within human genes, and more will be discovered in the coming years. These disorders share some clinical similarities, as well as some differences, which are summarized here. These diseases have unusual clinical genetic properties related to the dynamic nature of CAG repeat expansions, including instability of the repeat expansion in meiosis, particularly male meiosis; a strong correlation between onset age and size of the repeat expansion; anticipation (earlier disease onset in succeeding generations); new mutations arising from unstable, mutable alleles with a high‐normal CAG repeat number; and reduced penetrance for alleles in the lowaffected range. Much more remains to be learned about the molecular biology and clinical pathophysiology of this new class of genetic diseases.SummaryIn the last six years, seven neurodegenerative diseases have been found to be caused by expansions of intragenic CAG repeat sequences. The diseases share a variable (usually adult) age of onset, which is highly dependent on the length of the CAG repeat, and effects on multiple systems within the central and peripheral nervous systems. The cerebral cortex is not a primary site of pathology for any of the diseases, and organs other than the nervous system are not primarily affected (except for SBMA). The diseases differ in their primary site of neuropathology, and for that reason have widely varying neurologic profiles. The distributions of normal and abnormal CAG repeat sizes vary among the diseases, and suggest that different mechanisms of mutagenesis or disease pathogenesis could exist for the different disorders.The dynamic nature of trinucleotide repeat mutations has clarified a number of clinical and genetic observations in these diseases. New mutations arising from mutable normal alleles have been reported for some of the diseases. The tendency to further expansion of an expanded allele provides a molecular correlate to the clinical observation of anticipation (171). Sex‐ and disease‐dependent meiotic instability correlates with the observation of a paternal bias among juvenile onset cases for HD, SCA1 and DRPLA. Finally, reduced penetrance for alleles at the low end of the abnormal range has been observed for some (but not all) diseases in the group. Detection of CAG repeat expansions is relatively easy and inexpensive in the clinical laboratory, and molecular diagnosis has greatly improved diagnostic accuracy for this group of disorders. However, a full understanding of the biology and pathophysiology of this new class of mutations is still to come, and is awaited eagerly by clinicians and patients alike.
March 1997‐4 Year Old Girl with Ring Chromosome 22 and Brain Tumor
Authors: Rubio Ana 
Published: January 2008

Case AbstractA four year old Caucasian girl with a constitutional ring chromosome 22 abnormality and developmental delay presented with increasing ataxia and a six week history of non‐specific symptoms. Imaging studies demonstrated a large third ventricular tumor with apparent involvement of the septum. Microscopic and immunohistochemical studies demonstrated an atypical teratoid/rhabdoid tumor. This tumor is compared and contrasted to peripheral malignant rhabdoid tumors and central primitive neuroectodermal tumors. The role of a putative tumor suppressor gene on the long arm of chromosome 22 in the pathogenesis of these tumors is also discussed.
Cytokines and Reperfusion in Ischemic Stroke
Authors: Garcia Julio H. , Liu Kai‐Feng , Ye Zhu‐Rong 
Published: January 2008

The clinical syndrome known as ischemic stroke, secondary to the occlusion of an intracranial artery, once considered an ineluctably catastrophic event, may be susceptible of being improved through the application of newly developed therapeutic interventions. The evidence favoring this optimistic outlook is based on three separate but probably interrelated observations: (1) There exists a lapse of hours, perhaps days, between the ictus (i.e., the appearance of a focal neurologic deficit or stroke) and the time when irreversible tissue injury (i.e., widespread pannecrosis) becomes demonstrable. This time interval, generally known as the therapeutic window, may be measured in hours or days depending on the degree or severity of the post occlusive ischemia. (2) Reopening the artery, within a reasonable period of time, has beneficial effects in terms of: (a) improving the neurologic function, and (b) decreasing the numbers of necrotic neurons as well as preventing the appearance of pannecrosis or infarction. (3) The progression from the early ischemic changes (potentially reversible) to the development of an infarct may be influenced by the effects of selected cytokines, in particular those of interleukin 1 (IL‐1).In this review we illustrate selected structural features of the various brain lesions induced by either permanent or transient arterial occlusions. Moreover, we discuss the possible Involvement of interleukins in the progression of the brain lesion based on experiments utilizing the administration of a human recombinant IL‐1 receptor antagonist. Combined with the efforts aimed at restoring the normal circulatory conditions, therapeutic interventions that inhibit specific cytokines may contribute to improve the outcome of ischemic strokes.
Primitive Neuroectodermal Tumors of the Central Nervous System
Authors: Rorke Lucy Balian , Trojanowski John Q. , Lee Virginia MY , Zimmerman Robert A. , Sutton Leslie N. , Biegel Jaclyn A. , Goldwein Joel W. , Packer Roger J. 
Published: January 2008

Controversial issues relating to the pathobiology and classification of central nervous system primitive neuroectodermal tumors (PNETs) have plagued neuropathologists for more than 70 years. Hypotheses advanced in the mid‐1920's have remained as fixed concepts in contemporary literature, largely consequent to repetitious support by a small number of neuropathologists despite a growing body of information discrediting these ideas from neuroembryologists, oncologists, neuroscien‐tists and pathologists.Attention has largely focused upon PNETs arising in the cerebellum (commonly known as medul‐loblastomas [MBs]), because about 80% of central nervous system (CNS) PNETs originate in this site. It has been asserted that the 20% which do not are biologically different, although most individuals agree that the histological features of PNETs that occur in different sites throughout the CNS are indistinguishable from those growing in the cerebellum.The historical aspects of this controversy are examined in the face of evidence that there is, in fact, a unique class of CNS tumors which should appropriately be regarded as primitive neuroectodermal in nature. Specifically, a number of different approaches to the problem have yielded data supporting this hypothesis. These approaches include the identification of patterns of expression among a variety of cellular antigens (demonstrated by the use of immunopathological techniques), molecular analyses of cell lines derived from these tumors, experimental production of PNETs and molecular genetic analyses.Differences of opinion among surgeons, oncologists and radiotherapists are typically resolved by conducting cooperative studies of patients with these tumors who are diagnosed and treated at multiple centers.
November 1996 — Premature Baby with Lethargy and Coma
Authors: Hevner Robert , Sobel Raymond A. 
Published: January 2008

Case AbstractA premature male baby (28 weeks gestational age) was delivered by Cesarean section and required ventilation for respiratory distress syndrome during the first postnatal week. Four weeks postnatally, he had an episode of transient renal failure followed by lethargy leading to coma. Ultrasound changes were interpreted as intraventricular hemorrhage, grade 2. The baby died 31 days after birth. Autopsy showed bilateral thrombosis of the deep cerebral veins.
December 1996 — Cervicomedullary Tumor
Authors: Hamilton Ronald L. 
Published: January 2008

Case AbstractA cervicomedullary tumor in a 22‐month‐old female with an eight‐month history of symptoms showed the histological features of a pilocytic astrocytoma but had many areas of palisading cells identical to those described in polar spongioblastomas. The tumor recurred 18 months later and showed predominately pilocytic features. The case is used to discuss polar spongioblastomas and tumors which can histologically simulate them.
Pathology and Immunocytochemistry of a Kuru Brain
Authors: Hainfellner Johannes A. , Liberski Pawel P. , Guiroy Don C. , Cervénaková Larisa , Brown Paul , Gajdusek D. Carleton , Budka Herbert 
Published: January 2008

We report here results of modern staining techniques including anti‐prion protein (PrP) immunocytochemistry to a set of archival brain specimens of a 16 year‐old male who died from kuru in 1967. Brain suspensions transmitted disease to chimpanzees and New World monkeys. The PrP gene is homozygous for valine at the polymorphic codon 129. Histology shows neuronal loss, spongiform change, and astrogliosis. Lesions are maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, striatum, and thalamus, and are accentuated in middle and deep cerebral cortical layers. PrP accumulates as diffuse synaptic type deposits and mostly unicentric plaques. PrP deposition is maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, basal ganglia, and cerebellar cortex. Plaques are prominent in the striatum, thalamus, and granular layer of cerebellar cortex. Meticulous examination reveals only rare “florid” plaques with surrounding vacuolation.We conclude that 1) pathology including immunomorphology of PrP deposition in this kuru brain is within the lesion spectrum of Creutzfeldt‐Jakob disease although plaques are unusually prominent and widespread; 2) kuru does not share the neuropathological hallmarks of the new Creutzfeldt‐Jakob disease variant recently reported in the UK and France; 3) topographic prominence of PrP deposition parallels that of spongiform change and/or astrogliosis.
July 1996 — Precocious Puberty
Authors: Hamilton Ronald L. 
Published: January 2008

Case AbstractA 4 year old girl presented with precocious puberty. She had pubic hair, breast buds and showed a height and weight well above the 95th percentile. An MRI scan of the head revealed a discrete mass in the tuber cinereum which was surgically removed. Microscopic examination showed a hypothalamic hamartoma. The clinical, radiologic and microscopic findings in this case are “classic” for hypothalamic hamartoma Other clinical presentations are discussed. The patient's symptoms have regressed following surgery and there has been no regrowth in six months.
Virulence and resistance in a mosquito–microsporidium interaction
Authors: Michalakis Yannis , Bédhomme Stéphanie , Biron David G. , Rivero Ana , Sidobre Christine , Agnew Philip 
Published: January 2008

AbstractWe review the results of a series of experiments involving Aedes aegypti and its microsporidian parasite Vavraia culicis to illustrate how intra‐specific competition and parasitism shape life history traits. More specifically these experiments showed that some major components of virulence are host condition‐dependent in this system, while others are not. We also briefly discuss the ways through which V. culicis modifies the physiological functioning of its host. We discuss the implications of these results for studies of host – parasite interactions in general and propose ways through which our studies could contribute to vector control and management programs.
Multilaboratory Testing of Antifungal Combinations against a Quality Control Isolate of
Candida krusei
Authors: Chaturvedi Vishnu , Ramani Rama , Ghannoum Mahmoud A. , Killian Scott B. , Holliday Nicole , Knapp Cindy , Ostrosky-Zeichner Luis , Messer Shawn A. , Pfaller Michael A. , Iqbal Naureen J. , Arthington-Skaggs Beth A. , Vazquez Jose A. , Sein Tin , Rex John H. , Walsh Thomas J. 
Published: January 2008

ABSTRACT

Candida krusei
ATCC 6258 was tested by eight laboratories using 96-well plates containing checkerboard pairwise combinations of amphotericin B (AMB), posaconazole (PSC), caspofungin (CSP), and voriconazole (VRC). The methodology led to reproducible results across the laboratories. All drug combinations yielded MICs lower than the MICs of any two drugs tested singly, and combinations of AMB, PSC, CSP, and VRC were indifferent (no antagonism) by summations of fractional inhibitory concentration.
In Vitro Model of Colonization Resistance by the Enteric Microbiota: Effects of Antimicrobial Agents Used in Food-Producing Animals
Authors: Wagner R. Doug , Johnson Shemedia J. , Cerniglia Carl E. 
Published: January 2008

ABSTRACT

A bioassay was developed to measure the minimum concentration of an antimicrobial drug that disrupts the colonization resistance mediated by model human intestinal microbiota against
Salmonella
invasion of Caco-2 intestinal cells. The bioassay was used to measure the minimum disruptive concentrations (MDCs) of drugs used in animal agriculture. The MDCs varied from 0.125 μg/ml for some broad-spectrum antimicrobial drugs (e.g., streptomycin) to 16 μg/ml for drugs with limited spectra of antimicrobial activity (e.g., lincomycin). The acceptable daily intake (ADI) residue concentration calculated on the basis of the MDCs were higher for erythromycin, lincomycin, and tylosin than the ADI residue concentrations calculated on the basis of the MICs. The MDC-based ADI values for apramycin, bacitracin, neomycin, novobiocin, penicillin G, streptomycin, tetracycline, and vancomycin were lower than the reported MIC-based ADI values. The effects of antimicrobial drugs at their MDCs on the bacterial composition of the microbiota were observed by denaturing gradient gel electrophoresis of 16S rRNA sequences amplified by PCR. Changes in the population composition of the model colonization resistance microbiota occurred simultaneously with reduced colonization resistance. The results of this study suggest that direct assessment of the effects of antimicrobial drugs on colonization resistance in an in vitro model can be useful in determining ADI values.
In Vitro Interactions of Micafungin with Amphotericin B against Clinical Isolates of
Candida
spp
Authors: Serena Carolina , Mariné Marçal , Quindós Guillermo , Carrillo Alfonso J. , Cano J. F. , Pastor F. Javier , Guarro Josep 
Published: January 2008

ABSTRACT

The in vitro activity of amphotericin B in combination with micafungin was evaluated against 115 isolates representing seven species of
Candida
. Overall, the percentages of synergistic interactions were 50% and 20% when the MIC-2 (lowest drug concentration to cause a prominent reduction in growth) and MIC-0 (lowest drug concentration to cause 100% growth inhibition) end point criteria, respectively, were used. Antagonism was not observed. Some of the interactions were confirmed by time-kill assays.
Isolation of Imipenem-Resistant
Enterobacter
Species: Emergence of KPC-2 Carbapenemase, Molecular Characterization, Epidemiology, and Outcomes
Authors: Marchaim Dror , Navon-Venezia Shiri , Schwaber Mitchell J. , Carmeli Yehuda 
Published: January 2008

ABSTRACT

The prevalence of isolation of imipenem-resistant
Enterobacter
(IRE) strains is rising, with potential serious consequences in terms of patients' outcomes and general care. The study objective was to define the various epidemiological aspects of the isolation of these strains in comparison to cases of isolation of imipenem-susceptible
Enterobacter
(ISE) strains. Molecular analysis of IRE strains included genotyping and defining the presence of carbapenemases. We conducted a matched retrospective case-control study of patients hospitalized from April 2003 to December 2006. Each IRE case was matched with an ISE case by age and source of isolation. A multivariate analysis using conditional logistic regression was performed to compare the two patient groups. There were 33 cases of IRE isolations during the study period. Twenty isolates were analyzed and found to belong to three distinct pulsotypes. Cell extracts of all of these isolates hydrolyzed imipenem. PCR and sequencing revealed that these isolates harbored a KPC-2 gene. In multivariate analysis, a high invasive-device score (
P
= 0.02) remained a predictor of IRE isolation. The mortality in the IRE group was 33%, compared to 9% among controls. Being an IRE case was significantly associated with increased mortality after controlling for confounders in a multivariate model (odds ratio, 8.3 ± 8.6; 95% confidence interval, 1.07 to 64;
P
= 0.043). Resistance to imipenem due to
bla
KPC-2
among
Enterobacter
isolates has occurred in several clones in Tel Aviv, affecting particularly patients with multiple invasive devices compared to ISE controls. IRE infections are associated with increased mortality. Enhanced measures to control the hospital spread of IRE are warranted.
Activity of Tigecycline against Coryneform Bacteria of Clinical Interest and
Listeria monocytogenes
Authors: Salas Carlos , Calvo Jorge , Martínez-Martínez Luis 
Published: January 2008

ABSTRACT

The activities of tigecycline and eight other agents were evaluated against 220 coryneform bacteria and 42
Listeria monocytogenes
isolates. All strains were inhibited by tigecycline at 0.5 μg/ml, except for 11
Corynebacterium striatum
strains that were inhibited at 1 μg/ml. Tigecycline shows good in vitro activity against coryneform bacteria and
L. monocytogenes
.
Diversity of Extended-Spectrum β-Lactamases and Class C β-Lactamases among Cloacal
Escherichia coli
Isolates in Belgian Broiler Farms
Authors: Smet Annemieke , Martel An , Persoons Davy , Dewulf Jeroen , Heyndrickx Marc , Catry Boudewijn , Herman Lieve , Haesebrouck Freddy , Butaye Patrick 
Published: January 2008

ABSTRACT

A total of 295 ceftiofur-resistant
Escherichia coli
isolates were obtained from 489 cloacal samples collected at five different Belgian broiler farms with the aim to evaluate the diversity of this resistance at the farm level. Strains were examined for resistance against β-lactam antibiotics and other antimicrobial agents by using disk diffusion tests. Three different β-lactam resistance phenotypes suggested the presence of an extended-spectrum β-lactamase (ESBL), a class C β-lactamase, or the combination of an ESBL with a class C β-lactamase. Seventy-six percent of these isolates also showed acquired resistance to other antimicrobial agents. After genotyping by repetitive extragenic palindromic-PCR, 51 unrelated
E. coli
strains were selected for further analyses. Isoelectric focusing and sequencing of the amplicons obtained in PCRs for the detection of genes encoding broad-spectrum β-lactamase enzymes revealed the following ESBLs: TEM-52 (13.2%), TEM-106 (2%), CTX-M-1 (27.4%), CTX-M-2 (7.8%), CTX-M-14 (5.9%), and CTX-M-15 (2%). The only plasmidic AmpC β-lactamase found in this study was the CMY-2 enzyme (49%). Mutations in the promoter and attenuator regions of the chromosomal
ampC
gene were found only in association with
bla
CMY-2
genes and ESBL genes. The combination of an ESBL (CTX-M-1) with a plasmidic AmpC β-lactamase (CMY-2) was found in 7.8% of the isolates. These data show that ceftiofur-resistant
E. coli
strains are often present in cloacal samples of broilers at the farm level in Belgium. The diversity of broad-spectrum β-lactamases among these isolates is high, and they may act as a reservoir of ESBL and
ampC
genes.
NK Cells and Gamma Interferon Coordinate the Formation and Function of Hepatic Granulomas in Mice Infected with theFrancisella tularensisLive Vaccine Strain
Authors: Bokhari Sirosh M. , Kim Kee-Jun , Pinson David M. , Slusser Joyce , Yeh Hung-Wen , Parmely Michael J. 
Published: January 2008

ABSTRACTHost innate immune responses to many intracellular pathogens include the formation of inflammatory granulomas that are thought to provide a physical barrier between the microbe and host. Because two common features of infections with the live vaccine strain (LVS) ofFrancisella tularensiswithin the mouse liver are the formation of granulomas and the production of gamma interferon (IFN-γ), we have asked what role IFN-γ plays in hepatic granuloma formation and function.Francisellaantigens were predominantly localized within granulomas of the livers of mice infected withF. tularensisLVS 4 days postinfection. Hepatic granulomas also contained large numbers of dying cells, some of which coexpressed the F4/80 macrophage antigen and activated caspase-3. IFN-γ-deficient mice did not form normal numbers of hepatic granulomas and showed widely disseminatedFrancisellaantigens within the liver. The incidence of cell death within hepatic granulomas also decreased significantly in the absence of IFN-γ. Inducible NO synthase (iNOS) expression was restricted to the granulomas of wild-type mice but was not seen for IFN-γ-deficient mice. Cell death within granulomas was also significantly decreased for iNOS-deficient mice. The predominant IFN-γ-expressing cells in the liver were NK cells. Depleting NK cells resulted in the expression of bacterial antigens and iNOS outside the granulomas and the appearance of extensive hepatic focal necrosis. These findings indicate that IFN-γ and hepatic NK cells that are activated duringF. tularensisLVS infections regulate hepatic granuloma formation, the spatial containment of infection, the expression of iNOS, and the induction of cell death within the liver.
Flagellin-Dependent and -Independent Inflammatory Responses following Infection by EnteropathogenicEscherichia coliandCitrobacter rodentium
Authors: Khan Mohammed A. , Bouzari Saeid , Ma Caixia , Rosenberger Carrie M. , Bergstrom Kirk S. B. , Gibson Deanna L. , Steiner Theodore S. , Vallance Bruce A. 
Published: January 2008

ABSTRACTEnteropathogenicEscherichia coli(EPEC) and the murine pathogenCitrobacter rodentiumbelong to the attaching and effacing (A/E) family of bacterial pathogens. These noninvasive bacteria infect intestinal enterocytes using a type 3 secretion system (T3SS), leading to diarrheal disease and intestinal inflammation. While flagellin, the secreted product of the EPECfliCgene, causes the release of interleukin 8 (IL-8) from epithelial cells, it is unclear whether A/E bacteria also trigger epithelial inflammatory responses that are FliC independent. The aims of this study were to characterize the FliC dependence or independence of epithelial inflammatory responses to direct infection by EPEC orC. rodentium. Following infection of Caco-2 intestinal epithelial cells by wild-type and ΔfliCEPEC, a rapid activation of several proinflammatory genes, including those encoding IL-8, monocyte chemoattractant protein 1, macrophage inflammatory protein 3α (MIP3α), and β-defensin 2, occurred in a FliC-dependent manner. These responses were accompanied by mitogen-activated protein kinase activation, as well as the Toll-like receptor 5 (TLR5)-dependent activation of NF-κB. At later infection time points, a subset of these proinflammatory genes (IL-8 and MIP3α) was also induced in cells infected with ΔfliCEPEC. The nonmotile A/E pathogenC. rodentiumalso triggered similar innate responses through a TLR5-independent but partially NF-κB-dependent mechanism. Moreover, the EPEC FliC-independent responses were increased in the absence of the locus of enterocyte effacement-encoded T3SS, suggesting that translocated bacterial effectors suppress rather than cause the FliC-independent inflammatory response. Thus, we demonstrate that infection of intestinal epithelial cells by A/E pathogens can trigger an array of proinflammatory responses from epithelial cells through both FliC-dependent and -independent pathways, expanding our understanding of the innate epithelial response to infection by these pathogens.