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Variant Forms (variant + form)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	33%
Humanities and Social Sciences	11%

Selected Abstracts

An autosomal dominant genetically heterogeneous variant of rolandic epilepsy and speech disorder

EPILEPSIA, Issue 6 2008
Steven L. Kugler
Summary We report a three generation pedigree with 11 of 22 affected with a variant form of rolandic epilepsy, speech impairment, oromotor apraxia, and cognitive deficit. The core features comprised nocturnal rolandic seizures, interictal centrotemporal spike waves with early age of onset and late age of offset. The transmission of the phenotype was consistent with autosomal dominant inheritance, with variable expressivity but no evidence of anticipation. We found evidence that the seizure and speech traits may be dissociated. No abnormalities were found by cytogenetic analysis. Linkage analysis excluded loci at 11p, 15q, 16p12, and Xq22 for related phenotypes, suggesting genetic heterogeneity. [source]

Pathogenic mutations cause rapid degradation of lysosomal storage disease-related membrane protein CLN6,

HUMAN MUTATION, Issue 2 2010
Anna-Katherina Kurze
Abstract One variant form of late infantile neuronal ceroid lipofuscinosis is an autosomal recessive inherited neurodegenerative lysosomal storage disorder caused by mutations in the CLN6gene. The function of the polytopic CLN6 membrane protein localized in the endoplasmic reticulum is unknown. Here we report on expression studies of three mutations (c.368G>A, c.460-462delATC, c.316insC) found in CLN6 patients predicted to affect transmembrane domain 3 (p.Gly123Asp), cytoplasmic loop 2 (p.Ile154del) or result in a truncated membrane protein (p.Arg106ProfsX26), respectively. The rate of synthesis and the stability of the mutant CLN6 proteins are reduced in a mutation-dependent manner. None of the mutations prevented the dimerization of the CLN6 polypeptides. The particularly rapid degradation of the p.Arg106ProfsX26 mutant which is identical with the mutation in the murine orthologue Cln6 gene in the nclf mouse model of the disease, can be strongly inhibited by proteasomal and partially by lysosomal protease inhibitors. Both degradative pathways seem to be sufficient to prevent the accumulation/aggregation of the mutant CLN6 polypeptides in the endoplasmic reticulum. © 2009 Wiley-Liss, Inc. [source]

Maternal MTHFR variant forms increase the risk in offspring of isolated nonsyndromic cleft lip with or without cleft palate,,

HUMAN MUTATION, Issue 1 2004
F. Pezzetti
Abstract The pathogenesis of cleft lip with or without cleft palate (CL/P) is complex; its onset could be due to the interaction of various genetic and environmental factors. Recently MTHFR functional polymorphisms were found to increase the risk of this common malformation; however, this finding is still debated. We investigated 110 sporadic CL/P patients, their parents and 289 unrelated controls for c.665C>T (commonly known as 677C>T; p.Ala222Val) and c.1286A>C (known as 1298A>C; p.Glu429Ala) polymorphism in the MTHFR gene. Transmission disequilibrium test (TDT) showed no distortion in allele transmission. Nevertheless, association studies revealed significant differences in allele frequencies between mothers of CL/P patients and controls. This work supports the hypothesis that a lower MTHFR enzyme activity in pregnant women, mostly related to the c.665C>T variant form, is responsible for a higher risk of having CL/P affected offspring. © 2004 Wiley-Liss, Inc. [source]

Cytogenetic analysis of pediatric anaplastic large cell lymphoma,

PEDIATRIC BLOOD & CANCER, Issue 3 2010
Lara Mussolin PhD
Abstract Background Anaplastic large cell lymphoma (ALCL) constitutes approximately 15% of pediatric and 3% of adult non-Hodgkin lymphomas. Most pediatric cases harbor the reciprocal translocation t(2;5)(p23;q35), involving the alk gene. Cytogenetic studies of ALCL have mostly been published as case-reports. The aim of this study was to determine the cytogenetic profiles of a series of pediatric ALCL and to compare them with pediatric and adult ALCL from the literature. Methods Eighteen children treated at our Institution were studied by standard cytogenetic analysis and RT-PCR for the specific t(2;5) translocation product. Comparative analysis was performed on our findings and on the karyotypes of 48 pediatric and 39 adult ALCL reported in the literature. Results Karyotype was obtained in 16/18 ALCL: 9 showed translocation t(2;5) and 1 an alk variant form. Structural and numeric chromosomal abnormalities were identified in both pediatric and adult series. Trisomies were found preferentially in pediatric patients (P,=,0.013) and monosomies in adults (P,=,0.038). Trisomy 7 was found in 22% (13/59) of pediatric cases with abnormal karyotype and only in 5% (2/38) of adults; monosomy of chromosome 13 in 13% (5/38) of adults and only in 2% (1/59) of pediatric patients and monosomy of chromosome 15 in 16% (6/38) of adults and in none of the pediatric ALCL. Conclusion Our data suggest that pediatric and adult ALCL are characterized by different numerical chromosomal abnormalities. Larger prospective studies may elucidate their potential prognostic impact. Pediatr Blood Cancer. 2010;55:446,451. © 2010 Wiley-Liss, Inc. [source]

Socio-political control in urban China: changes and crisis*

THE BRITISH JOURNAL OF SOCIOLOGY, Issue 4 2001
Raymond W. K. Lau
ABSTRACT This paper examines urban China's socio-political control crisis under the impact of economic reforms as an epitome of a more general social crisis. The traditional urban institutional form of socio-political control in the People's Republic of China (PRC), the work unit form of control, is a variant of age-old forms. The latter's reproduction in variant form in the former was premised upon the fact that the PRC's industrialization was carried out by a peasant-based party creating a new working class of rural migrants engaged in non-market production and exchange. The persistence of non-market economic relations ensured this form of control's continued reproduction. Post-1978 market-oriented reforms have undermined this form. As the emergence of new forms has been slow, a socio-political control crisis has arisen, at a time when millions of urban employees are being thrown out of work. In dealing with the crisis, the official trade union, an organic constituent institution of the work unit form of control, plays a prominent part, in being given the tasks of sustaining this decaying form, and preventing and defusing potential social explosion. Yet, the very economic reform programme that has undermined the work unit form of control, is also gravely weakening the union. [source]

Evaluation of infant methylenetetrahydrofolate reductase genotype, maternal vitamin use, and risk of high versus low level spina bifida defects,

BIRTH DEFECTS RESEARCH, Issue 3 2003
Kelly A. Volcik
BACKGROUND Several studies have suggested that homozygosity for the C677T 5,10-methylenetetrahydrofolate reductase (MTHFR) variant is a potential risk factor for neural tube defects (NTDs), as individuals homozygous for the C677T allele have slightly elevated homocysteine concentrations under conditions of low folic acid intake. It has been hypothesized that maternal folic acid supplementation prevents NTDs by partially correcting reduced MTHFR activity associated with the variant form of the enzyme. METHODS Genomic DNA was extracted from newborn screening blood spots obtained from 145 infants with spina bifida (SB) and 260 nonmalformed control infants. The MTHFR C677T genotype was determined by restriction enzyme digestion of PCR amplification products with Hinf1. We investigated whether infant MTHFR genotype influenced the risk for the anatomic level of the SB lesion (high vs. low); we also explored whether maternal vitamin use influenced this risk. RESULTS Compared to controls, the frequency of SB infants with the homozygous 677 TT genotype was greatest in those infants with high level SB defects (26%; odds ratio [OR] = 2.9; 95% confidence interval [CI] = 0.9,10.1) than for those with low level SB defects (22%; OR = 1.8; 95% CI = 0.9,3.2). Furthermore, homozygous 677TT infants whose mothers did not use vitamins containing folic acid had a modestly increased risk of SB (OR = 1.8; 95% CI = 0.8,3.9), with this risk increasing more than three-fold (OR = 5.5; 95% CI = 0.8,28.1) for those infants with high level SB defects whose mothers did not use vitamins. CONCLUSIONS Based upon our observations, it is suggested that the association between the infant MTHFR homozygous variant genotype and spina bifida risk may be conditional upon both lesion level and maternal vitamin use. Birth Defects Research (Part A) 67:154,157, 2003. © 2003 Wiley-Liss, Inc. [source]

Idiopathic and allergic rhinitis show a similar inflammatory response

CLINICAL OTOLARYNGOLOGY, Issue 6 2000
D.G. Powe
Hypothesis. Idiopathic and allergic rhinitics have similar mucosal mast cell and IgE+ cell distribution. Introduction. The pathophysiology of idiopathic rhinitis (IR) is unknown but patients differ from those with allergic rhinitis (AR) in that they do not express IgE. Our study is novel because we investigated: (1) three study groups chosen prospectively using strict selection criteria over a 4-year period; and (2) mast cell and IgE+ cell counts were on full-thickness, full-length inferior turbinate mucosa. Methods. Patient groups: allergic (n = 17); idiopathic: (n = 16); and normal controls (n = 9). Immunohistochemistry: mast cell and IgE+ cell detection using anti-mast cell tryptase and anti-IgE antibodies with an avidin-biotin (peroxidase) complex on paraffin processed tissue. Morphometry: sections were divided into three strata comprising an epithelial layer and two submucosal layers. Statistics: Mann,Whitney non-parametric analysis. ,,= 0.05, ,,= 0.2. Results. The power of the study was 89%. Mast cells (P = 0.03) and IgE+ cells (P < 0.05) were significantly increased in the epithelium of idiopahtic and allergic rhinitis mucosa compared to the normal control. More IgE+ cells were counted in the AR and IR groups compared to the controls in all three strata. Conclusion. Mast cells and IgE+ cells are involved in the pahtophysiology of IR. We propose that IR may be a variant form of AR involving a localized IgE-mediated inflammatory response. [source]

Osteopontin and the skin: multiple emerging roles in cutaneous biology and pathology

EXPERIMENTAL DERMATOLOGY, Issue 9 2009
Franziska Buback
Abstract:, Osteopontin (OPN) is a glycoprotein expressed by various tissues and cells. The existence of variant forms of OPN as a secreted (sOPN) and intracellular (iOPN) protein and its modification through post-translational modification and proteolytic cleavage explain its broad range of functions. There is increasing knowledge which receptors OPN isoforms can bind to and which signaling pathways are activated to mediate different OPN functions. sOPN interacts with integrins and CD44, mediates cell adhesion, migration and tumor invasion, and has T helper 1 (Th1) cytokine functions and anti-apoptotic effects. iOPN has been described to regulate macrophage migration and interferon-, secretion in plasmacytoid dendritic cells. Both sOPN and iOPN, through complex functions for different dendritic cell subsets, participate in the regulation of Th cell lineages, among them Th17 cells. For skin disease, OPN from immune cells and tumor cells is of pathophysiological relevance. OPN is secreted in autoimmune diseases such as lupus erythematosus, and influences inflammation of immediate and delayed type allergies and granuloma formation. We describe that OPN is overexpressed in psoriasis and propose a model to study OPN function in psoriatic inflammation. Through cytokine functions, OPN supports immune responses against Mycobacteria and viruses such as herpes simplex virus. OPN is also implicated in skin tumor progression. Overexpression of OPN influences invasion and metastasis of melanoma and squamous cell carcinoma cells, and OPN expression in melanoma is a possible prognostic marker. As OPN protein preparations and anti-OPN antibodies may be available in the near future, in-depth knowledge of OPN functions may open new therapeutic approaches for skin diseases. [source]

Putting flesh and polish on autoimmune hepatitis and moving the disease of exclusion to inclusion,

HEPATOLOGY, Issue 4 2010
Albert J. Czaja
Autoimmune hepatitis emerged during an era when concepts of neonatal immune tolerance, clonal selection of lymphocytes, and "forbidden clones" of activated immune cells were forming. The diagnosis had to be deduced from circumstantial evidence and by exclusion of other conditions. The goals of this review are to demonstrate how a clinician nonscientist can contribute to the maturation of autoimmune hepatitis and to illustrate the principles of clinical investigation that can be applied broadly to other projects. Autoimmune hepatitis initially had to be distinguished from other diseases, and improvements in the tests for viral and immune markers were instrumental in this regard. Diversification of the clinical phenotype to accommodate acute severe, asymptomatic, elderly, and variant forms enhanced the pertinence of the disease, and the formation of the International Autoimmune Hepatitis Group standardized the diagnosis, interconnected investigators, and promoted global acceptance of the condition. Subsequent studies refined current corticosteroid-based therapies, identified prognostic markers, assessed genetic predispositions, explored new pharmacological agents, and forecast the emergence of cellular and molecular interventions. Good fortune, stimulating mentors, career dedication, practical goal selection, protocol compliance, compulsive record keeping, personal resilience, and strong collaborations were the bases for progress. Autoimmune hepatitis exemplifies an evolutionary process in the science of autoimmunity and the people committed to its study. Lessons derived from this experience can be far-reaching. (HEPATOLOGY 2010;52:1177-1184) [source]

Maternal MTHFR variant forms increase the risk in offspring of isolated nonsyndromic cleft lip with or without cleft palate,,

Natural history of hepatocellular carcinoma including fibrolamellar and hepato-cholangiocarcinoma variants

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2002
Kunio Okuda
Abstract The natural history of hepatocellular carcinoma (HCC) varies greatly with the global region, because the carcinogenic factors are not the same among countries. Besides the clinicopathological factors such as tumor characteristics, sex, and age, background liver disease is a major determinant of prognosis. Hepatocellular carcinoma, mainly associated with chemical carcinogens such as aflatoxin, does not have severe background cirrhosis, and grows quickly, whereas HCC developing in association with a virus in a cirrhotic liver generally grows more slowly, and the severity of cirrhosis is the major prognostic factor. The median survival of untreated sub-Saharan African patients is less than 1 month from diagnosis, contrasted by an average survival of 4 months in virus-induced HCC associated with cirrhosis. Tumor characteristics, such as size, number, and growth speed, which vary considerably from case to case, affect the prognosis. Vascular (portal) invasion portends a poor prognosis, and ,-fetoprotein levels also correlate with prognosis. Several distinct clinical types of HCC occur, namely diffuse-type HCC caused by rapid portal spread of cancer cells, febrile-type caused by poorly differentiated sarcomatoid cancer cells, and cholestatic HCC caused by intraductal invasion; all have a short survival. There are several histological variant forms: combined hepato-cholangiocarcinoma behaves like HCC, with a poorer prognosis because of more frequent lymph node metastases; fibromellar carcinoma, which is relatively common in young Caucasian adults, has a good prognosis if diagnosed early, permitting resection; and cholangiolocellular carcinoma, which derives from the canalicular epithelium, is indistinguishable from HCC, with a similar prognosis. © 2002 Blackwell Publishing Asia Pty Ltd [source]

The role of gene,environment interaction in the aetiology of human cancer: examples from cancers of the large bowel, lung and breast

JOURNAL OF INTERNAL MEDICINE, Issue 6 2001
L. A. Mucci
Abstract. Mucci LA, Wedren S, Tamimi RM, Trichopoulos D, Adami H.-O. (Harvard School of Public Health, Boston, MA, USA; and Karolinska Institutet, Stockholm, Sweden) The role of gene,environment interaction in the aetiology of human cancer: examples from cancers of the large bowel, lung and breast. J Intern Med 2001; 249: 477,493. It has become increasingly clear that cancer can be considered neither purely genetic nor purely environmental. A relatively new area of cancer research has focused on the interaction between genes and environment in the same causal mechanism. Primary candidates for gene-environment interaction studies have been genes that encode enzymes involved in the metabolism of established cancer risk factors. There are common variant forms of these genes (polymorphisms), which may alter metabolism and increase or decrease exposure to carcinogens, thus impacting the risk of cancer. We present an overview of enzymes involved in carcinogen metabolism, present epidemiological tools to evaluate gene-environment interactions, and provide examples from cancers of the breast, lung and large bowel. [source]

Indexicality and experience: Exploring the meanings of /aw/-monophthongization in Pittsburgh1

JOURNAL OF SOCIOLINGUISTICS, Issue 1 2008
Barbara Johnstone
In this paper we test the hypothesis that monophthongal /aw/ is semiotically associated with local identity in Pittsburgh. We compare results of an experimental task that directly elicits participants' sense of the indexical value of /aw/-monophthongization with the occurrence of this variant in the same people's speech. People who hear monophthongal /aw/ as an index of localness are unlikely to have this feature in their own speech, and many of the people who do monophthongize /aw/ do not associate this variant with localness. Exploring how four of these participants talk about this feature and its meanings, we show that the indexical meanings of speech features can vary widely within a community, and we illustrate the danger of confusing the meaning assigned by hearers to a linguistic form with the meaning users would assign to it. We suggest that a phenomenological approach, attending to the multiplicity and indeterminacy of indexical relations and to how such relations arise historically and in lived experience, can lead to a more nuanced account of the distribution of social meanings of variant forms than can studies of perception or production alone. [source]

Unifying clones with a generative programming technique: a case study

JOURNAL OF SOFTWARE MAINTENANCE AND EVOLUTION: RESEARCH AND PRACTICE, Issue 4 2006
Stan Jarzabek
Abstract Software clones,similar program structures repeated in variant forms,increase the risk of update anomalies, blow up the program size and complexity, possibly contributing to high maintenance costs. Yet, programs are often polluted by clones. In this paper, we present a case study of cloning in the Java Buffer library, JDK 1.5. We found that at least 68% of the code in the Buffer library was contained in cloned classes or class methods. Close analysis of program situations that led to cloning revealed difficulties in eliminating clones with conventional program design techniques. As a possible solution, we applied a generative technique of XVCL (XML-based Variant Configuration Language) to represent similar classes and methods in generic, adaptable form. Concrete buffer classes could be automatically produced from the generic structures. We argue, on analytical and empirical grounds, that unifying clones reduced conceptual complexity and enhanced the changeability of the Buffer library at rates proportional to code size reduction (68%). We evaluated our solution in qualitative and quantitative ways, and conducted a controlled experiment to support this claim. The approach presented in the paper can be used to enhance genericity and changeability of any program, independently of an application domain or programming language. As the solution is not without pitfalls, we discuss trade-offs involved in its project application. Copyright © 2006 John Wiley & Sons, Ltd. [source]

A confusing world: what to call histology of three-dimensional tumour margins?

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2007
M Moehrle
Abstract Complete three-dimensional histology of excised skin tumour margins has a long tradition and, unfortunately, a multitude of names as well. Mohs, who introduced it, called it ,microscopically controlled surgery'. Others have described it as ,micrographic surgery', ,Mohs' micrographic surgery', or simply ,Mohs' surgery'. Semantic confusion became truly rampant when variant forms, each useful in its own way for detecting subclinical outgrowths of malignant skin tumours, were later introduced under such names as histographic surgery, systematic histologic control of the tumour bed, histological control of excised tissue margins, the square procedure, the perimeter technique, etc. All of these methods are basically identical in concept. All involve complete, three-dimensional histological visualization and evaluation of excision margins. Their common goal is to detect unseen tumour outgrowths. For greater clarity, the authors of this paper recommend general adoption of ,3D histology' as a collective designation for all the above methods. As an added advantage, 3D histology can also be used in other medical disciplines to confirm true R0 resection of, for example, breast cancer or intestinal cancer. [source]

A bacterial conjugation machinery recruited for pathogenesis

MOLECULAR MICROBIOLOGY, Issue 5 2003
Anja Seubert
Summary Type IV secretion systems (T4SS) are multicomponent transporters of Gram-negative bacteria adapted to functions as diverse as DNA transfer in bacterial conjugation or the delivery of effector proteins into eukaryotic target cells in pathogenesis. The generally modest sequence conservation between T4SS may reflect their evolutionary distance and/or functional divergence. Here, we show that the establishment of intraerythrocytic parasitism by Bartonella tribocorum requires a putative T4SS, which shares an unprecedented level of sequence identity with the Trw conjugation machinery of the broad-host-range antibiotic resistance plasmid R388 (up to 80% amino acid identity for individual T4SS components). The highly conserved T4SS loci are collinear except for the presence of numerous tandem gene duplications in B. tribocorum, which mostly encode variant forms of presumed surface-exposed pilus subunits. Conservation is not only structural, but also functional: R388 mutated in either trwD or trwH encoding essential T4SS components could be trans -complemented for conjugation by the homologues of the B. tribocorum system. Conservation also includes the transcription regulatory circuit: both T4SS loci encode a highly homologous and interchangeable KorA/KorB repressor system that negatively regulates the expression of all T4SS components. This striking example of adaptive evolution reveals the capacity of T4SS to assume dedicated functions in either DNA transfer or pathogenesis over rather short evolutionary distance and implies a novel role for the conjugation systems of widespread broad-host-range plasmids in the evolution of bacterial pathogens. [source]

C-peptide microheterogeneity in type 2 diabetes populations

PROTEOMICS - CLINICAL APPLICATIONS, Issue 1 2010
Paul E. Oran
Abstract Purpose: The purpose of this study was to investigate naturally occurring C-peptide microheterogeneity in healthy and type 2 diabetes (T2D) populations. Experimental design: MS immunoassays capable of simultaneously detecting intact C-peptide and variant forms were applied to plasma samples from 48 healthy individuals and 48 individuals diagnosed with T2D. Results: Common throughout the entire sample set were three previously unreported variations of C-peptide. The relative contribution of one variant, subsequently identified as C-peptide (3-31), was found to be more abundant in the T2D population as compared to the healthy population. Dipeptidyl peptidase IV is suspected to be responsible for this particular cleavage product, which is consistent with the pathophysiology of T2D. Conclusions and clinical relevance: C-peptide does not exist in the human body as a single molecular species. It is qualitatively more heterogeneous than previously thought. These results lay a foundation for future studies devoted to a comprehensive understanding of C-peptide and its variants in healthy and diabetic populations. [source]

Reduced expression and novel splice variants of ING4 in human gastric adenocarcinoma,

THE JOURNAL OF PATHOLOGY, Issue 1 2009
Ming Li
Abstract ING4, a new member of the ING (inhibitor of growth) family of tumour suppressor genes, has been found to be deleted or down-regulated in gliomas, breast tumours, and head and neck squamous cell carcinomas. The goal of the present study was to investigate whether the expression and alternative splicing of ING4 transcripts are involved in the initiation and progression of stomach adenocarcinoma. ING4 mRNA and protein expression was examined in gastric adenocarcinoma tissues and human gastric adenocarcinoma cell lines by RT-PCR, real-time RT-PCR, tissue microarray immunohistochemistry, and western blot analysis. Alterations in ING4 transcripts were determined through sequence analysis of ING4 cDNA. Our data showed that ING4 mRNA and protein were dramatically reduced in stomach adenocarcinoma cell lines and tissues, and significantly less in female than in male patients. We also found that reduced ING4 mRNA expression correlated with the stage of the tumour. Interestingly, by sequence analysis, we discovered five novel aberrantly spliced variant forms of ING4_v1 and ING4_v2. These variants cause a codon frame-shift and, eventually, deletion of the NLS or PHD domain contributing to the mislocalization of p53 and/or HAT/HDAC complexes and, subsequently, altered gene expression in gastric adenocarcinoma. These results suggest that attenuated and aberrant ING4 expression may be involved in the initiation and progression of stomach adenocarcinoma. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]