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PubMed1999

mGluR3 and mGluR5 are the predominant metabotropic glutamate receptor mRNAs expressed in hippocampal astrocytes acutely isolated from young rats.

The metabotropic glutamate receptors (mGluRs) that are expressed and not expressed on astrocytes in the brain have not been defined. While immunohistochemistry and in situ mRNA hybridization have been used on a limited basis to address this question, they do not readily enable the proportion of astrocytes expressing a particular mRNA or protein to be determined. Also, for many receptors, expression by cultured astrocytes does not reflect in situ expression. In this study, therefore, we examined expression of mRNA for all the mGluRs except mGluR6 by single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) in freshly isolated hippocampal astrocytes from postnatal day P1-10 rats, as an additional approach to address the question of which mGluRs are expressed on astrocytes in situ. The astrocytic nature of the cells was supported by simultaneously measuring mRNA for the astrocytic marker glial fibrillary acidic protein (GFAP) from the same cells. In these studies, the percentage of cells showing GFAP mRNA expression was the same as the percentage of cells showing immunocytochemical staining for GFAP. We found that only mGluR3 and mGluR5 mRNAs were significantly present in GFAP mRNA(+) cells. The mGluR5 PCR products were primarily of the "a" splice variant. mGluR1, 2, 4, 7, and 8 were very rarely or never detected. mGluR6 mRNA level was too low in whole rat brain and hippocampus to warrant examination. These results show that interpretation of effects involving mGluR3 or 5 activation in the hippocampus of young rats needs to also consider effects due to astrocytes.

Animals↗

PubMed2004

Elevated catecholamine metabolites in patients with Costello syndrome.

Costello syndrome is a rare congenital anomaly syndrome with a predisposition to specific tumors, including neuroblastoma, rhabdomyosarcoma, and transitional cell carcinoma of the bladder. The increased risk for solid tumors led to the proposal of a tumor screening protocol. A screening test for neuroblastoma consists of measuring catecholamine metabolites in urine, an assay that may also be used for diagnostic confirmation of a suspected catecholamine secreting tumor. We report eight patients with Costello syndrome with elevated catecholamine metabolites, vanillylmandelic acid (VMA) and/or homovanillic acid (HVA), in urine. Each patient had additional laboratory and/or imaging studies. None of the patients was found to have a neuroblastoma or another catecholamine secreting tumor. In two cases, the assays were performed because the patients were symptomatic with diaphoresis and hypertension, respectively, and in the other six cases the assays were performed in order to screen for neuroblastoma. The pathophysiology for the catecholamine metabolite abnormality in these patients with Costello syndrome remains unclear. However, it appears that in this patient group an elevation above the normal limit, defined as 2 standard deviations (SD) above the mean for age, is more likely to be a variant, rather than a sign of a neuroblastoma. Thus, it may be prudent not to use this assay as a screening test, and to take the frequently elevated results into consideration when interpreting diagnostic assays.

Abnormalities, Multiple↗

PubMed1996

Re-examination of the evidence for low-dimensional, nonlinear structure in the human electroencephalogram.

We have re-examined single channel EEG data obtained from normal human subjects. In the original analysis, calculation of the correlation dimension with the Grassberger-Procaccia algorithm produced results consistent with and interpretation of low-dimensional behavior. The re-examination suggests that the previous indication of low-dimensional structure was an artifact of autocorrelation in the oversampled signal. Calculations with a variant of the Grassberger-Procaccia algorithm modified to be less sensitive to autocorrelations, and comparison with linear gaussian surrogate data, indicate that these data may be more appropriately modeled by linearly filtered noise. Discriminant analysis further indicates that the correlation dimension is a poor discriminator for distinguishing between EEGs recorded at rest and during periods of cognitive activity. It remains possible that the application of other nonlinear measures or the examination of multichannel EEG data may resolve structures not found in these calculations.

Adult↗

PubMed2006

More than one variant of Listeria monocytogenes isolated from each of two human cases of invasive listeriosis.

Two variants of Listeria monocytogenes were isolated from blood cultures from each of two patients with listeriosis. Each variant displayed a two-band difference in DNA profile from the other by pulsed-field gel electrophoresis. Although this difference in profile is insufficient to distinguish clearly between the variants, the possibility of co-infection with different strains of L. monocytogenes needs to be considered. We suggest that more than one colony should be selected for molecular typing to aid interpretation during investigation of the sources and routes of Listeria infection.

DNA, Bacterial↗

PubMed2004

Karyotype stability of the DT40 chicken B cell line: macrochromosome variation and cytogenetic mosaicism.

The DT40 transformed chicken B-cell line is an important and widely used vertebrate cell line. Knowledge of the 'wild-type' DT40 karyotype is a significant consideration for most research applications and for extrapolation of results to normal cells. Here we present data indicating that (1) modal karyotype differences exist between DT40 cultures from different sources, (2) DT40 cultures are cytogenetically mosaic, and (3) the mosaic features can change over time with media conditions influencing the degree and type of non-modal karyotypes that emerge. In addition to the previously reported trisomy for chromosome 2, a monosomy for chromosome 4 and a variant 4p- are described. The macrochromosomal variation and mosaic nature of the DT40 system should alert researchers using this important cell line to consider whether such variation will impact experimental results and interpretation. The results are discussed in regard to current knowledge of cytogenetic anomalies associated with chicken cancers.

Aneuploidy↗

PubMed1997

A re-examination of the relationship between shyness, attributional style, and depression.

Alfano, Joiner, and Perry (1994) used analysis of variance and analysis of covariance in a sample of college students to demonstrate that attributional style mediates between shyness and depression, as opposed to depression mediating between shyness and attributional style. They suggested, however, the hypothetical possibility of a third model, in which negative attributional style, rather than shyness, is the independent variable, and shyness serves as a mediator between attributional style and depression. In the current study, this alternative model was tested by using LISREL to reanalyze the Alfano et al. data. Results showed that this third model, with shyness as the mediating variable, fit the model quite poorly, in contrast to the preferred model of Alfano et al., which fit quite well. However, variants of this model, in which shyness functionally precedes both attributional style and depression, fit the data better. The substantive implications of this model for counseling practice and the methodological cautions about interpreting cross-sectional data for temporal sequences are discussed.

Depression↗

PubMed2004

Selection versus demography: a multilocus investigation of the domestication process in maize.

The domestication of maize (Zea mays ssp. mays) from its wild ancestor (Zea mays ssp. parviglumis) led to a loss of genetic diversity both through a population bottleneck and through directional selection at agronomically important genes. In order to discriminate between those effects and to investigate the nature of the domestication bottleneck, we analyzed nucleotide diversity data from 12 chromosome 1 loci in parviglumis. We found an average loss of nucleotide diversity of 38% across genes, but this average was skewed downward by four putatively selected loci (tb1, d8, ts2, and zagl1). To better understand the domestication process, we used the coalescent with recombination to simulate bottlenecks under various lengths and population sizes. For each locus, we determine the likelihood of the observed data using three summary statistics: the number of segregating sites, an estimate of the population recombination parameter, and Tajima's D. Based on the eight neutrally evolving loci, a model with a bottleneck had a significantly higher likelihood than a model without one. The four putatively selected loci had significantly different likelihood optimums than the neutral loci, and this approach confirmed that ts2 and d8 were selected either during domestication or breeding. Overall, the best-fitting models had a bottleneck in which the population size and the bottleneck duration had a ratio of approximately 4- to approximately 5; for example, if the initial domestication event occurred over a 500-year period, the population size was roughly 2,000 to 2,500 individuals. However, this range did vary with the summary statistic used to assess the fit of simulations to data. In this context, Tajima's D performed poorly as a goodness-of-fit statistic, probably because Z. mays ssp. parviglumis has a frequency spectrum that is significantly skewed toward low-frequency variants. Finally, we found that demography is unlikely to account for the previously observed positive correlation between nucleotide diversity and the population-recombination parameter in maize, leaving this observation difficult to interpret.

Amino Acid Sequence↗

PubMed1999

Epithelioid cell histiocytoma: a simulant of vascular and melanocytic neoplasms.

Epithelioid cell histiocytoma (ECH) is an unusual and still poorly recognized variant of benign fibrous histiocytoma. Epithelioid cell histiocytoma differs from most benign fibrous histiocytomas in five important ways: the predominance of epithelioid cells, relative lack of secondary elements (such as giant cells, foamy, or hemosiderin-laden macrophages), relative sharp circumscription, prominent vascularity, and centering in the papillary dermis in most cases. A strong resemblance to melanocytic and vascular lesions has been noted, and a recent case was reported with features suggesting endothelial origin. Fifteen new cases of ECH, including one example of the rare deep cellular variant, are presented herein, with emphasis on features mimicking vascular and melanocytic neoplasms. Labeling with endothelial markers, including previously unreported CD-31 labeling, showed abundant vascular staining, which may be challenging to interpret, but which does not indicate an endothelial origin of ECH.

Adult↗

PubMed2005

Rare mutations at codon 103 of HIV-1 reverse transcriptase can confer resistance to non-nucleoside reverse transcriptase inhibitors.

BACKGROUND: The K103N mutation in HIV-1 reverse transcriptase (RT) confers high-level resistance to current non-nucleoside reverse transcriptase inhibitors (NNRTI). The prevalence and resistance profile of HIV-1 with other substitutions at RT codon 103 is less well documented. METHODS: K103 substitutions among over 70,000 clinical samples submitted for routine antiretroviral resistance testing at two independent centres were examined. Phenotypic resistance profiles of isolates harboring rare K103 variants in the absence of known NNRTI-associated resistance mutations were retrieved from Virco's correlative genotype/phenotype database. Genotyped samples with known treatment histories were retrieved from the British Columbia Centre for Excellence in HIV/AIDS database. Site-directed mutants containing K103 variants were constructed and phenotyped. RESULTS: K103N, R and S were observed in 29, 1.8, and 0.9% of Virco isolates and in 16, 1.5 and 0.4% of British Columbia isolates. K103T/Q/H substitutions were observed only rarely (<0.2%). The prevalence of unusual codon 103 substitutions remained stable over 5 years, except K103S, which increased over fourfold in both datasets. K103R/Q-containing clinical isolates remained phenotypically susceptible to NNRTI, whereas K103S/T/H-containing isolates showed over 10-fold decreased NNRTI susceptibility. Among patients with a known treatment history, K103S/T/H were observed primarily in individuals failing NNRTI-containing regimens. Site-directed mutants confirmed decreased susceptibility to NNRTI in K103S/T/H-containing recombinants. CONCLUSION: Variants at HIV RT codon 103 other than K103N are observed relatively rarely in clinical isolates, but K103 S, T and H confer decreased susceptibility to NNRTI. These data are relevant for interpretive genotype algorithms and in the design of assays specific to RT codon 103 mutations.

Amino Acid Substitution↗

PubMed1995

Monoclonal anti-D specificity and Rh D structure: criteria for selection of monoclonal anti-D reagents for routine typing of patients and donors.

The Rh blood group system is the next most important to the ABO system in terms of its clinical significance in blood transfusion. It is vital to the safe, efficient practice of transfusion medicine that Rh D phenotyping tests are selected, executed and interpreted correctly. However, the Rh D blood group antigen has been shown to be subject to many phenotypic variations, and different reagents and typing techniques vary in their ability to detect these variants. The range of D-positive phenotypes are reviewed in terms of their reactivity with monoclonal antibody reagents and their clinical significance. In view of the available evidence, it is suggested that patient typing can be safely achieved by the duplicate use of one high-avidity or two very similar IgM monoclonal anti-D reagents that detect most variants except category DVI in simple tube or microplate saline tests. Antiglobulin testing for weak D should not be carried out on patient samples. Donor typing can be safely achieved by the use of the same monoclonal, used in parallel with a polyclonal anti-D reagent that detects DVI on sensitive automated equipment.

Antibodies, Monoclonal↗

PubMed2002

Analysis of phylogenetic relationship of Cylindrocarpon lichenicola and Acremonium falciforme to the Fusarium solani species complex and a review of similarities in the spectrum of opportunistic infections caused by these fungi.

An emerging pattern of similarity in medical case reports led to a project to compare the phylogenetic affinities of two well-known tropical fungal opportunistic pathogens, Cylindrocarpon lichenicola and Acremonium falciforme, to members of the Fusarium solani species complex. C. lichenicola and A. falciforme, despite their deviating conidial morphologies, were shown via sequencing of the ribosomal large subunit to be well instituted within a clade mainly consisting of typical F. solani strains and other species until recently considered variants of F. solani. The original name Fusarium lichenicola C. B. Massalongo is reestablished, and the new combination F. falciforme is made. Recognition of these species as fusaria is necessary for correct interpretation of current and future molecular diagnostic tests. Reevaluation of species morphology in light of the molecular findings showed that certain features, especially elongate filiform conidiophores with integrated terminal phialides, facilitate correct microscopic classification of these atypical Fusarium species. There is a strong and underrecognized overlap in the spectra of cases caused by members of the F. solani clade, particularly ocular infections, mycetomas, and, in the neutropenic host, disseminated and other serious systemic infections. A novel synthesis of case reports shows that patients from areas with warm climates may develop a distinctive fusarial intertrigo caused by F. solani, Fusarium lichenicola, or Fusarium oxysporum.

Acremonium↗

PubMed1994

Animal-derived antigenic variants of foot-and-mouth disease virus type A12 have low affinity for cells in culture.

We recently have shown that binding of foot-and-mouth disease virus (FMDV) to cells in culture requires an arginine-glycine-aspartic acid (RGD) sequence in the G-H loop of the capsid protein VP1 (P. W. Mason, E. Rieder, and B. Baxt, Proc. Natl. Acad. Sci. USA 91:1932-1936, 1994). In this report, we show that FMDV type A12 viruses found in infected bovine tongue tissue (BTT) differ from their tissue culture-grown derivatives at amino acid residues near the RGD. Viruses genetically engineered to contain VP1 sequences found in animal tissue (BTT viruses) were antigenically different from their tissue culture derivatives and bound to BHK cells more poorly than did the tissue culture-adapted viruses. Passage of the genetically engineered BTT viruses in BHK cells resulted in the rapid selection of variants with cell-binding properties, antigenic characteristics, and sequences typical of tissue culture-adapted viruses. These data indicate that residues near the RGD are critical for cell binding and that interpretations of antigenic variation of FMDV can be affected by virus cultivation in vitro.

Amino Acid Sequence↗

PubMed2005

The origins of polypoidal choroidal vasculopathy.

BACKGROUND/AIM: There are two theories on the pathogenesis of polypoidal choroidal vasculopathy (PCV): variants in choroidal neovascularisation (CNV) and inner choroidal vessel abnormalities. On indocyanine green angiography (IGA) with a video camera system, PCV has a characteristic appearance, but inadequate image quality has made detailed interpretation difficult. This study aims to improve imaging, using confocal scanning laser ophthalmoscopy (SLO), to elucidate the pathogenesis of PCV. METHODS: High speed IGA with confocal SLO of 45 eyes (44 patients) showed typical PCV findings of a branching vascular network and polypoidal lesions. RESULTS: Vessels comprising branching networks began to fill simultaneously with the surrounding choroidal arteries in 38 eyes. Small numbers of vessels filling within a branching network, in the arterial and arteriovenous phases of IGA, showed focal dilatation, constriction, and tortuousity. Vessel abnormalities, corresponding to polypoidal lesions, existed within a network in eight eyes and included loops similar in calibre to network vessels, and numerous microaneurysmal dilatations of small vessels. Vessel pulsation was seen in 24 eyes. CONCLUSION: PCV is caused by inner choroidal vessel abnormalities, not CNV.

Aged↗

PubMedDate not supplied

Photoconvertible fluorescent protein EosFP: biophysical properties and cell biology applications.

EosFP is a fluorescent protein from the coral Lobophyllia hemprichii that changes its fluorescence emission from green to red upon irradiation with near-UV light. Here we present the spectroscopic properties of wild-type EosFP and a variety of monomeric and dimeric mutants and provide a structural interpretation of its oligomerization and photoconversion, which is based on X-ray structure analysis of the green and red species that we reported recently. Because functional expression of the monomeric EosFP variant is limited to temperatures of 30 degrees C, we have developed a tandem dimer. This construct, in which two EosFP subunits are connected by a flexible 12 amino acid linker, expresses well after fusion with the androgen and endothelin A receptors at 37 degrees C. A variety of applications in cellular imaging, developmental biology and automated high-content screening applications are presented, which demonstrate that EosFP is a powerful tool for in vivo monitoring of cellular processes.

Amino Acids↗

PubMed2002

Identification of chromosomal translocations in leukemias by hybridization with oligonucleotide microarrays.

BACKGROUND AND OBJECTIVES: Identification of chromosomal rearrangements is important for a precise risk-stratified diagnosis of hematologic malignancies. As the number of known translocations, specific for different types of leukemia increases, it takes ever more time and increasing amounts of patient's material to screen a single patient with individual polymerase chain reactions (PCR). The aim of this study was to develop a new approach combining specificity with high-throughput sufficient for rapid screening of clinical samples for the presence of numerous translocations. DESIGN AND METHODS: We designed an oligonucleotide microarray and used hybridization with microarrays in combination with multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay for accurate and rapid identification of some major leukemias. The following translocations were used as prototypic: t(9;22) p210 and p190, t(4;11), t(12;21), and t(15;17). This approach was tested on five different cell cultures carrying translocations and on 22 clinical samples from leukemic patients. RESULTS: Distinctive hybridization signals were obtained for all types of chimeric transcripts from cell lines with translocations. Both the type of translocation and the splice variant were determined. The data demonstrated high specificity and reproducibility of the method. Analysis of the 22 clinical samples using the microarray-based approach showed complete agreement with standard PCR analysis. INTERPRETATION AND CONCLUSIONS: Our data suggest that oligonucleotide microarrays can be used as an efficient, alternative approach to the traditional post-PCR Southern blot analysis. The oligonucleotide microarray approach appears suitable for clinical screening of major risk-stratifying translocations in patients with leukemia.

Bone Marrow↗

PubMedDate not supplied

Thymus and thymoma: what's new?

The thymus is the prototype of lymphoid and epithelial organ that consists of lymphoid and epithelial cells. In spite of remarkable progresses made in the field of the immunohistochemical characterisation of the thymus parenchyma, the diagnosis of thymoma largely depends on the interpretation of conventional morphologic aspects. Histogenesis of this organ is a multi-step process, and many stages reproduce lesions and changes found in the adult thymus. The normal structure and its variants are extremely helpful to differentiate normal from pathologic aspects. Particular aspects of the thymus structures were shown in myasthenia gravis, despite the behaviour of thymoma in these patients is not clearly understood. Authors performed a detailed description of the conventional pathology of the thymoma, based on the new classifications, recently adopted. The immunohistochemical profile could be helpful in the diagnosis of many cases, and also seems to be useful in prediction of invasion that is the most important criterion in prognosis.

Humans↗

PubMed1988

The University of Florida sickle cell screening program for neonates: design and results.

During the first 18 months of a pilot program for sickle cell screening at the University of Florida College of Medicine, Gainesville, 2,058 black neonates were screened. An incidence of homozygous sickle disease of 0.5 percent was greater than that expected or predicted by carrier frequency (8.3 percent). Fifty percent of all infants with abnormal cord blood electrophoreses were retested. All infants with actual homozygous disease or other clinically significant variants had confirmation of their diagnosis and were channeled for appropriate care. A change of phenotypic diagnosis based on a follow-up sample was made in eight cases. Errors were either interpretational or through contamination of cord blood samples by maternal blood at the time of delivery. Although location of infants for retesting after discharge was made more difficult by the largely rural composition of the target population, certain measures were taken to improve patient retrieval: use of public health personnel; enlistment of the aid of private physicians in the community; and inclusion of information regarding the screening program in the hospital discharge packets of black mothers. It is concluded that screening programs serving rural populations can adequately identify infants with abnormal hemoglobin patterns while educating and caring for families of these infants in a cost-efficient and effective manner.

Anemia, Sickle Cell↗

PubMed1994

Classification of melanoma in adults and children.

After a brief history of the classification of melanoma in adults, this chapter describes the major features of the classic histogenetic types as well as of uncommon variants. Particular attention is paid to the meaning of controversial terms such as "minimal deviation" and "borderline." Specific problems associated with the classification of melanoma in children are also addressed, along with interpretation of atypical lesions resembling Spitz nevi.

Adult↗