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PubMed1997

A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells.

MDEG1 is a cation channel expressed in brain that belongs to the degenerin/epithelial Na+ channel superfamily. It is activated by the same mutations which cause neurodegeneration in Caenorhabditis elegans if present in the degenerins DEG-1, MEC-4, and MEC-10. MDEG1 shares 67% sequence identity with the recently cloned proton-gated cation channel ASIC (acid sensing ion channel), a new member of the family which is present in brain and in sensory neurons. We have now identified MDEG1 as a proton-gated channel with properties different from those of ASIC. MDEG1 requires more acidic pH values for activation and has slower inactivation kinetics. In addition, we have cloned from mouse and rat brain a splice variant form of the MDEG1 channel which differs in the first 236 amino acids, including the first transmembrane region. This new membrane protein, which has been called MDEG2, is expressed in both brain and sensory neurons. MDEG2 is activated neither by mutations that bring neurodegeneration once introduced in C. elegans degenerins nor by low pH. However, it can associate both with MDEG1 and another recently cloned H+-activated channel DRASIC to form heteropolymers which display different kinetics, pH dependences, and ion selectivities. Of particular interest is the subunit combination specific for sensory neurons, MDEG2/DRASIC. In response to a drop in pH, it gives rise to a biphasic current with a sustained current which discriminates poorly between Na+ and K+, like the native H+-gated current recorded in dorsal root ganglion cells. This sustained current is thought to be required for the tonic sensation of pain caused by acids.

Acid Sensing Ion Channels↗

PubMed2001

Ductal carcinoma in-situ arising in mammary-like glands of the vulva.

Recently a variant of cutaneous glands has been recognized in the anogenital region that combines the morphologic and immunohistochemical features of eccrine, apocrine, and mammary glands, so-called 'mammary-like glands of the vulva'. Carcinoma arising in mammary-like tissue of the vulva is a rare occurrence. So far, there have been 11 cases of primary, mammary-type invasive carcinoma and one case of in-situ carcinoma reported in the vulva. We describe an unusual case of ductal carcinoma in-situ without invasion arising in mammary-like glands of the vulva. A 57-year old woman presented with a 1-year history of a 1 cm nodule in the right labium majus. Excision showed ductal carcinoma in-situ with cribriform and papillary morphology in an adenosis-like lesion associated with mammary-like glands. No invasion into the stroma was identified. Immunostains were positive for gross cystic disease fluid protein 15 (GCDFP-15) and estrogen and progesterone receptors. An extensive survey including bilateral mammograms was negative. One year postoperatively, the patient shows no evidence of disease. To our knowledge, this represents the second case of DCIS associated with mammary-like glands of the vulva reported in the English literature.

Biomarkers↗

PubMed2007

Epidemic dynamics of two coexisting hepatitis C virus subtypes.

Hepatitis C virus (HCV) infection affects about 3% of the human population. Phylogenetic analyses have grouped its variants into six major genotypes, which have a star-like distribution and several minor subtypes. The most abundant genotype in Europe is the so-called genotype 1, with two prevalent subtypes, 1a and 1b. In order to explain the higher prevalence of subtype 1b over 1a, a large-scale sequence analysis (100 virus clones) has been carried out over 25 patients of both subtypes in two regions of the HCV genome: one comprising hypervariable region 1 and another including the interferon sensitivity-determining region. Neither polymorphism analysis nor molecular variance analysis (attending to intra- and intersubtype differences, age, sex and previous history of antiviral treatment) was able to show any particular difference between subtypes that might account for their different prevalence. Only the demographic history of the populations carrying both subtypes and analysis of molecular variance (AMOVA) for risk practice suggested that the route of transmission may be the most important factor to explain the observed difference.

Analysis of Variance↗

PubMed2025

MarkerMatch: A Proximity-Based Probe-Matching Algorithm for Joint Analysis of Copy-Number Variants from Different Genotyping Arrays.

MOTIVATION: Copy-number variants (CNVs) are a form of genetic structural variation with increasing importance in complex human disorders. Both DNA sequencing and microarray data can be used to call CNVs, which can be used in association tests, such as association between CNV number and disease status. Unlike genotypes, CNV detection in microarrays requires the use of observed intensity signals at each probe, which limits the imputability for analyses that span multiple array types. Thus far, a consensus set of probes (the intersection encompassing the probes that occur in common on all arrays) has been used to circumvent the problem of differing array-specific sensitivities. This has, however, led to excessive reduction in overall sensitivity of CNV calls as arrays can have an undesirably low overlap of probe sets. To overcome this limitation, we developed MarkerMatch, a proximity-based algorithm that matches probes across different genotyping microarrays to maximize the number of probes considered in the CNV calling algorithm, thereby increasing the resolution and sensitivity while preserving precision. RESULTS: By analyzing CNV calls from 4,906 individuals genotyped across three different arrays (Global Screening Array, Omni2.5 array, and Omni Express Exome array), we show that the MarkerMatch approach improves sensitivity by increasing the density of probes available for CNV calling while maintaining precision or improving it relative to the current practice (e.g., use of consensus probes only). We further demonstrate that MarkerMatch exceeds the output from current practice in terms of F1 score, Fowlkes-Mallows index, and Jaccard index. We also optimize MarkerMatch parameters, D MAX and Method, and find an optimal D MAX setting at 10kb, with no clear optimal candidate based on Method, indicating that parameters for this metric should be determined on a use case basis.

Journal Article↗

PubMed2006

Nearest neighbors by neighborhood counting.

Finding nearest neighbors is a general idea that underlies many artificial intelligence tasks, including machine learning, data mining, natural language understanding, and information retrieval. This idea is explicitly used in the k-nearest neighbors algorithm (kNN), a popular classification method. In this paper, this idea is adopted in the development of a general methodology, neighborhood counting, for devising similarity functions. We turn our focus from neighbors to neighborhoods, a region in the data space covering the data point in question. To measure the similarity between two data points, we consider all neighborhoods that cover both data points. We propose to use the number of such neighborhoods as a measure of similarity. Neighborhood can be defined for different types of data in different ways. Here, we consider one definition of neighborhood for multivariate data and derive a formula for such similarity, called neighborhood counting measure or NCM. NCM was tested experimentally in the framework of kNN. Experiments show that NCM is generally comparable to VDM and its variants, the state-of-the-art distance functions for multivariate data, and, at the same time, is consistently better for relatively large k values. Additionally, NCM consistently outperforms HEOM (a mixture of Euclidean and Hamming distances), the "standard" and most widely used distance function for multivariate data. NCM has a computational complexity in the same order as the standard Euclidean distance function and NCM is task independent and works for numerical and categorical data in a conceptually uniform way. The neighborhood counting methodology is proven sound for multivariate data experimentally. We hope it will work for other types of data.

Algorithms↗

PubMed1990

The equine fundus. III: Pathological variants.

A wide range of ophthalmoscopic variants are encountered during routine examination of the horse. Some result from minor anatomical anomalies, cause no significant effect on vision and may be considered to lie within the limits of 'biological normality'. Others are a consequence of pathological disruption of the anatomical integrity of the fundus, and may directly or indirectly affect the neurosensory retina and produce some degree of visual deficit. This paper illustrates the ophthalmoscopic appearance of a number of pathological variants of the anatomic fundus, and discusses their possible effect upon vision. Among the abnormalities discussed is peripapillary chorioretinitis, which commonly presents as the so-called peripapillary 'butterfly lesion'. It is concluded that, although this lesion may occur in conjunction with signs of more generalised posterior segment disease, eg posterior capsular cataract, in the absence of concurrent signs of anterior uveitis there is no reason to associate the lesion with equine recurrent uveitis (periodic ophthalmia).

Animals↗

PubMed2006

'Simplification' of responses of complex cells in cat striate cortex: suppressive surrounds and 'feedback' inactivation.

In mammalian striate cortex (V1), two distinct functional classes of neurones, the so-called simple and complex cells, are routinely distinguished. They can be quantitatively differentiated from each other on the basis of the ratio between the phase-variant (F1) component and the mean firing rate (F0) of spike responses to luminance-modulated sinusoidal gratings (simple, F1/F0 > 1; complex, F1/F0 < 1). We investigated how recurrent cortico-cortical connections affect the spatial phase-variance of responses of V1 cells in the cat. F1/F0 ratios of the responses to optimally oriented drifting sine-wave gratings covering the classical receptive field (CRF) of single V1 cells were compared to those of: (1) responses to gratings covering the CRFs combined with gratings of different orientations presented to the 'silent' surrounds; and (2) responses to CRF stimulation during reversible inactivation of postero-temporal visual (PTV) cortex. For complex cells, the relative strength of the silent surround suppression on CRF-driven responses was positively correlated with the extent of increases in F1/F0 ratios. Inactivation of PTV cortex increased F1/F0 ratios of CRF-driven responses of complex cells only. Overall, activation of suppressive surrounds or inactivation of PTV 'converted' substantial proportions (50 and 30%, respectively) of complex cells into simple-like cells (F1/F0 > 1). Thus, the simple-complex distinction depends, at least partly, on information coming from the silent surrounds and/or feedback from 'higher-order' cortices. These results support the idea that simple and complex cells belong to the same basic cortical circuit and the spatial phase-variance of their responses depends on the relative strength of different synaptic inputs.

Action Potentials↗

PubMed1978

Posterior polymorphous keratopathy.

Seven cases with posterior polymorphous changes of the cornea are reported. After clinical and pathological examination of the above cases, as well as a short review of the literature, the following points are made: (1) Some cases are congenital, being either familial or sporadic, but others are acquired. (2) The term "posterior polymorphous keratopathy" covers all the variants of the condition and is preferred to the traditional "posterior polymorphous dystrophy". (3) The congenital type is a mild variant of the mesodermal dysplasia, whereas the acquired type follows local disease. (4) The condition can be static, but over 50% of cases are slowly progressive, calling for penetrating keratoplasty.

Aged↗

PubMed1976

Pseudohermaphroditism due to XY gonadal absence syndrome.

A 21-year-old phenotypic female with a 46,XY chromosome complement and gonadal absence was studied. Basal levels of plasma immunoreactive luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, and oestradiol were measured. Pituitary sensitivity and reserve was evaluated by the exogenous administration of synthetic luteinizing hormone-releasing hormone. The episodic release of gonadotrophins was assessed by measuring plasma LH and FSH in plasma samples obtained at 20-minute intervals for a 4-hour period. Endocrine gonadal function was evaluated by a stimulation test with human chorionic gonadotrophin for 3 days. The results showed: a) persistently raised plasma levels of both LH and FSH; b) a pulsatile pattern of release of both gonadotrophins and a normal pituitary response to the synthetic hypothalamic decapeptide; and c) extremely low levels of circulating testosterone and oestradiol with a lack of response to the HCG stimulus. A careful exploratory laparotomy revealed absence of uterus, Fallopian tubes, the Mullerian portion of the vagina, and gonads. No Wolffian derivatives were found. A dissociation of testosterone and the so-called Jost substance effects during early sexual development may explain the findings in this unusual abnormality. The term 'XY gonadal absence syndrome' including five types of variants to designate this condition is proposed.

Disorders of Sex Development↗

PubMed1975

Trisomy 22.

The existence of a trisomy 22 has been definitely established by newer methods of karyotype analysis which permit distinction between the acrocentric chromosomes of group G. Trisomy 22 is much rarer than trisomy 21. This report presents presumptive evidence that the cat eye syndrome (CES), the so-called "trisomy 22" (T22), the intermediate cases (IM) with cardinal symptoms of CES and T22, and some cases of mental retardation with rather unspecific symptoms are variants of the same disease entity. For T22, CES and one abortive case the extra chromosome was clearly identified as number 22 chromosome with or without partial deletion of the long arm. An interesting and presently not fully understood feature of trisomy 22 is its frequent familial incidence.

Abnormalities, Multiple↗

PubMed1990

[Macroprolactinemia in a child].

An hyperprolactinemia, with basal serum prolactin levels ranging from 41 to 135 ng/ml was found to be coincidentally associated with psychosocial dwarfism in a 11 year-old boy. Sephadex G 100 exclusion chromatography showed that the predominating form of immunoreactive prolactin levels ranging from 41 to 135 ng/ml was found to be weight, differing from the regular occurrence of a 22 kilodalton major variant. Prolactin levels increased under TRH (increments between 29 and 76%) but were not blunted by bromocriptine at a dose of 2.5 mg/day. This so-called macroprolactinemia syndrome should be searched for whenever a discrepancy is noted between clinical symptoms and blood prolactin levels.

Adolescent↗

PubMed1990

[Ultrasonic evaluation of the course of the wound process after cholecystectomy].

The authors conducted 101 ultrasonic studies in patients in the early period after cholecystectomy. They studied the ultrasonic semeiotics of the course of the wound process in the zone of the operation. Three types of an uncomplicated course of the wound process in the zone of the operation were determined. An image of the sutured site of the gallbladder with no additional structures in the subhepatic space was encountered in most cases (variant I). In other cases (variants II and III) areas indicative of the accumulation of fluid in the subhepatic space and in the projection of the gallbladder site were visualized. This calls for a case follow-up and, in some cases, for preventive treatment.

Aged↗

PubMed1989

Structure and function of mycobacterial glycolipids and glycopeptidolipids.

Earlier work from this and other laboratories has revealed the presence within Mycobacterium spp. of three classes of glycolipid antigens which we have called the glycopeptidolipids, the lipooligosaccharides and the phenolic glycolipids. Representative structures of each from different species and sub-species have been proposed. More recently, new variants of these antigens and older structures have been analyzed by Fourier transform infrared, NMR, particularly at high temperatures, and, most notably, by fast atom bombardment and Californium desorption mass spectrometry. Extraordinary novelty and diversity were revealed, particularly at the distal non-reducing end of the oligosaccharide chains, marked by the presence of new branched-chain sugars, amino sugars and sugar acids. These epitopes and monoclonal antibodies to them have been used for the critical identification of mycobacteria. In addition, the pure antigens are the basis of specific serological tests for various mycobacterioses. The resurgence of interest in "atypical" mycobacteria stems from their occurrence as opportunistic pathogens in many patients with acquired immunodeficiency syndrome, although they have long been associated with pulmonary and other organ infections. Foremost among these mycobacteria are serovars of the Mycobacterium avium-Mycobacterium intracellulare complex (the M. avium complex). The surface antigens which differentiate these serovars are glycopeptidolipids, related to "mycoside C" and, accordingly, composed of a glycosylated lipopeptide "core", fatty acyl-D-Phe-D-alloThr-D-Ala-L-acanyl-O- (3,4-di-O-methyl-alpha-L-rhamnopyranoside), to which a haptenic oligosaccharide is linked at the threonine substituent; this oligoglycosyl unit is the source of type specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2003

The use of time-variant EEG Granger causality for inspecting directed interdependencies of neural assemblies.

Understanding of brain functioning requires the investigation of activated cortical networks, in particular the detection of interactions between different cortical sites. Commonly, coherence and correlation are used to describe interrelations between EEG signals. However, on this basis, no statements on causality or the direction of their interrelations are possible. Causality between two signals may be expressed in terms of upgrading the predictability of one signal by the knowledge of the immediate past of the other signal. The best-established approach in this context is the so-called Granger causality. The classical estimation of Granger causality requires the stationarity of the signals. In this way, transient pathways of information transfer stay hidden. The study presents an adaptive estimation of Granger causality. Simulations demonstrate the usefulness of the time-variant Granger causality for detecting dynamic causal relations within time intervals of less than 100 ms. The time-variant Granger causality is applied to EEG data from the Stroop task. It was shown that conflict situations generate dense webs of interactions directed from posterior to anterior cortical sites. The web of directed interactions occurs mainly 400 ms after the stimulus onset and lasts up to the end of the task.

Adult↗

PubMed1997

RHD/CE typing by polymerase chain reaction using sequence-specific primers.

BACKGROUND: Current DNA-based Rh system typing strategies may detect the two RH genes and their prevalent alleles, but they are known to fail sometimes, when rare RH alleles (e.g., D category phenotypes) are encountered. It is almost impossible to find a single DNA-based method that can accommodate the great heterogeneity within the human Rh system. STUDY DESIGN AND METHODS: An easy-to-perform DNA-based method for the detection of the two RH genes and their alleles, including variant RHD alleles, was developed. By the use of one RHD/C-, seven RHD-, and four RHCE-specific polymerase chain reactions, all triggered to work at identical thermocycling conditions, the DNA of 77 blood donors carrying weak D and that of 200 random donors with common D phenotype was investigated. In addition, 77 selected samples of ccDee and rare Rh system phenotypes were examined. RESULTS: Among 77 samples of weak D, one Rh33 and six DVI categories were detected, one of which showed new RHD-specific nucleotide patterns. In DFR and CCee samples, novel variant RHD alleles were found. RHD DNA types of 200 random donors were found to be concordant with their D phenotype. For RHE and RHe genotyping, a full correlation with serologic phenotypes was found. Our method for genotyping RHC and RHc failed in some cases, because of an already published RHc allelic variation, which we have called RHc(cyt48). An estimate of the frequency of this RHc(cyt48) allele in a white population was made. CONCLUSION: The presented exon-scanning RHD/CE polymerase chain reaction using sequence-specific primers complements current DNA-based Rh system typing strategies and is superior in the detection of variant RHD alleles.

Blood Donors↗

PubMed1987

Changes in the histone H2A variant H2A.Z and polyubiquitinated histone species in developing trout testis.

The trout histone H2A variant H2A.Z has been identified by its electrophoretic mobility on two-dimensional polyacrylamide gels and its N-terminal amino acid sequence. Similar to bovine H2A.Z and chicken H2A.F (also called H2A.Z and M1), the trout H2A.Z had a two-residue extension when aligned with trout H2A and a 67% sequence homology with the N-terminal portion of trout H2A. The first 29 amino acids of trout H2A.Z were identical with those of chicken H2A.F and differed from those of bovine H2A.Z at only one position. Thus, the N-terminal part of histone H2A.Z appears to be highly conserved. The levels of histone H2A.Z and ubiquitinated species of the histones H2A, H2A.Z, and H2B, which were detected with an anti-ubiquitin antibody, were studied at various stages of trout testis development. At the final stages of spermatogenesis in trout, histones are replaced by protamines. Ubiquitinated and diubiquitinated histone H2A remained at similar levels in early and late stage testis nucleohistone. In the late stage testis chromatin (nucleohistone), ubiquitinated histone H2A.Z was not detected, the level of ubiquitinated histone H2B was reduced, and the amount of diubiquitinated histone H2B increased. There was also a marked reduction in the level of histone H2A.Z. This observation suggests nucleosomes with this histone variant were selectively disassembled during the transition from nucleohistone to nucleoprotamine, indicating that protamine deposition is not a random process in rainbow trout.

Aging↗

PubMed2005

Association of intra- and extradural developmental venous anomalies, so-called venous angioma and sinus pericranii.

INTRODUCTION: We report a case of cerebellar venous angioma and parietal sinus pericranii. DISCUSSION: Venous angioma is classified as a developmental venous anomaly (DVA) because it is not a neoplasm but a variant that develops during embryogenesis. Sinus pericranii should be classified as extradural-type DVA. Although there have been few reports of association between these conditions, both are suspected to have the same pathogenesis, i.e., transient venous hypertension in the late embryonic period influencing venous development.

Central Nervous System Venous Angioma↗

PubMed1996

MAP2a, an alternatively spliced variant of microtubule-associated protein 2.

MAP2, a dendritically localized microtubule-associated protein (MAP), consists of a pair of high molecular mass (280 kDa) polypeptides, MAP2a and MAP2b, and several low molecular mass (70 kDa) proteins called MAP2c. Although MAP2b and MAP2c have been shown to arise via alternative splicing. It was not clear whether MAP2a is also created by alternative splicing or by posttranslational modification. Using epitope peptide mapping, we have demonstrated that an element specific to MAP2a is situated at its N-terminal end. A cDNA clone from an adult rat brain library was found to contain an additional 246 nucleotides situated at the 5' end of the 9-kb MAP2 mRNA. Antibodies generated against the encoded protein sequence recognize specifically MAP2a in rat brain homogenates. Moreover, although MAP2a, like MAP2b, is found in dendrites and cell bodies, its temporal appearance and cell type-specific distribution in rat brain differs from MAP2b.

Aging↗