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Molecular Findings (molecular + finding)
Selected AbstractsMechanisms of trophectoderm fate specification in preimplantation mouse developmentDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 3 2010Hiroshi Sasaki During preimplantation mouse development, embryos establish two distinct cell lineages by the time of blastocyst formation: trophectoderm (TE) and inner cell mass (ICM). To explain the mechanism of this cell fate specification, two classical models, namely the inside,outside model and polarity model have been proposed based on experimental manipulation studies on embryos. This review summarizes recent findings on the molecular mechanisms of fate specification, and discusses how these findings fit into the classical models. TE development is regulated by a transcription factor cascade, the core transcription factors of which are Tead4 and Cdx2. The transcriptional activity of Tead4 is regulated by the position-dependent Hippo signaling pathway, thus supporting the inside,outside model. In contrast, several findings support the polarity model; some other findings suggest different mechanisms. We also discuss how the two classical models could be further developed in the light of recent molecular findings. [source] Cytogenetic, FISH, and molecular studies in a case of B-cell chronic lymphocytic leukemia with karyotypic evolutionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5-6 2002Christian Chena Abstract:, We report the clinical, cytogenetic, fluorescence in situ hybridization (FISH) and molecular findings in a 54-yr-old male patient diagnosed with B-cell chronic lymphocytic leukemia (B-CLL), who showed progression to a diffuse large B-cell lymphoma (Richter's syndrome). Genetic studies were performed at diagnosis and during the Richter's transformation (RT). A clonal karyotype with two dicentric chromosomes, psu dic(12,21)(q24;q10) and dic(17,18)(p11.2;p11.2), was found. Both rearrangements were confirmed by FISH. Molecular cytogenetics analysis using p53 probe showed monoallelic loss of this tumor suppressor gene in 43.8% and 77.3% of cells for the first and the second studies, respectively). In both studies, deletions of D13S319 (18% and 12% of cells) and D13S25 loci (13% and 12% of cells) at 13q14 were found. Polymerase chain reaction analysis showed the MBR/JH rearrangement of the bcl-2 gene. FISH studies using LSI bcl-2/IgH probe allowed quantifying the clonal cell population with this rearrangement (4% and 6.6% of cells at diagnosis and RT, respectively). To our knowledge, this is the first case with a psu dic(12,21) described in B-CLL. The low percentage of cells with the 13q14 deletion and bcl-2/IgH rearrangement suggests that they were secondary events that resulted from clonal evolution. Our patient had a short survival (9 months) and a clear lack of response to several therapeutic agents, confirming the association of p53 gene deletion and karyotypic evolution with disease progression. [source] Stability of hippocampal place cell activity across the rat estrous cycle,HIPPOCAMPUS, Issue 2 2005Jennifer Tropp Abstract Findings from both in vitro and in vivo studies have shown that estrogen exerts pronounced effects on hippocampal morphology and physiology. The degree to which these molecular findings influence hippocampal processing in freely behaving animals is unclear. The present study assessed the effect of the estrous cycle on hippocampal place cells in naturally cycling rats during two behavioral states. Female Sprague-Dawley rats were trained to alternate on a U-shaped runway for food reinforcement. Single-unit recordings of hippocampal CA1 cells were conducted under two conditions: (1) at rest on a holder, and (2) running on the maze. Spatial firing characteristics of the cells were examined at different stages of the estrous cycle (i.e., diestrus, proestrus, and estrus). Specifically, information was collected on (1) mean firing rates; (2) basic place field parameters; and (3) changes in the firing dynamics of these cells (e.g., burst properties). The findings showed a decrease in mean firing rate on the maze during proestrus. However, other basic measures of spatial tuning and burst properties were unchanged. The current study suggests that there is relative stability of hippocampal place cells across the estrous cycle during a well-trained task. © 2004 Wiley-Liss, Inc. [source] INTER- AND INTRASPECIFIC VARIATION OF THE PSEUDO-NITZSCHIA DELICATISSIMA COMPLEX (BACILLARIOPHYCEAE) ILLUSTRATED BY RRNA PROBES, MORPHOLOGICAL DATA AND PHYLOGENETIC ANALYSES,JOURNAL OF PHYCOLOGY, Issue 2 2006Nina Lundholm A study of 25 cultures tentatively identified as Pseudo-nitzschia delicatissima (Cleve) Heiden, and originating from geographically widely distributed locations, showed both morphological and genetic variation among strains. Use of rRNA-targeted DNA probes on 17 different strains showed large variation in the hybridization patterns. Detailed morphological studies placed the isolates into three groups. The sample on which the neotype of P. delicatissima is based was also examined, and used to establish the morphological identity of P. delicatissima. Phylogenetic analyses of 16 strains, based on sequences of internal transcriber spacer 1 (ITS1), 5.8S and ITS2 of the nuclear-encoded rDNA, supported the morphological observations and the hybridization studies, and revealed large genetic variation among strains. A combination of the morphological and molecular findings resulted in the description of two new species, P. decipiens sp. nov. and P. dolorosa sp. nov. P. dolorosa has a mixture of one or two rows of poroids in the striae whereas P. delicatissima always has two rows. In addition, P. dolorosa has wider valves and a lower density of poroids. P. decipiens differs from P. delicatissima by a higher density of striae on the valve face as well as a higher density of poroids on the girdle bands. Among the strains referred to P. delicatissima, an epitype was selected. Large genetic variation was found among the P. delicatissima strains and a subdivision into two major clades represent cryptic species. [source] Complications of type 1 diabetes: new molecular findingsMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 4 2008Alin Stirban MD Abstract Interventions targeting the treatment of diabetic complications have not been nearly as successful as initially estimated, despite a marked improvement in therapeutic options for diabetes. The need for understanding why some very promising interventions have failed demands a closer look at the pathomechanisms of the complications. Great strides have been made in understanding the pathology, and several important hypotheses have emerged in recent years. On this basis, Brownlee and coworkers suggested a unifying hypothesis integrating various mechanisms discussed in past years with an overproduction of reactive oxygen species as an initiating cause. This hypothesis and further hypotheses, as well as mechanisms, are highlighted in this article. The field of pathomechanisms of diabetic complications is very wide, and any attempt to completely cover it within a single article is unrealistic. Therefore, our purpose is to present the most relevant concepts underlying diabetic complications in an attempt to contribute to a better understanding and pinpoint areas that warrant further research. Mt Sinai J Med 75:328,351, 2008. © 2008 Mount Sinai School of Medicine [source] Genetics of cardiovascular diseases: An overviewNURSING & HEALTH SCIENCES, Issue 2 2005Carmen T Ramirez edd, acnp(c), apn-g(c) Cardiovascular disease is the leading cause of illness and death in the USA, as well as other countries. Advances in genetics have led researchers to identified associations between a number of cardiac syndromes and diagnostic molecular findings. Therefore, a more precise understanding of the molecular pathways involved in cardiovascular diseases is clinically significant. Current literature suggests that while etiologies remain complex, a number of cardiovascular diseases can be linked to specific metabolic inheritable factors. A broad multifactorial model is gradually being replaced with disease specific models where independent genetic and/or teratogenic pathways may lead to a particular outcome. These genetic pathways include chromosome deletions, disruptions (translocations), duplications of particular genetic regions, point mutations involving single genes, or alteration in the ability for a gene to be transcribed into a functional protein. In this review the molecular mechanisms underlying cardiovascular diseases and their clinical manifestations will be explained. [source] A single-center experience in 20 patients with infantile malignant osteopetrosis,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2009Evelina Mazzolari Infantile malignant osteopetrosis (IMO) includes various genetic disorders that affect osteoclast development and/or function. Genotype,phenotype correlation studies in IMO have been hampered by the rarity and heterogeneity of the disease and by the severity of the clinical course, which often leads to death early in life. We report on the clinical and molecular findings and treatment in 20 consecutive patients (11 males, nine females) with IMO, diagnosed at a single center in the period 1991,2008. Mean age at diagnosis was 3.9 months, and mean follow-up was 66.75 months. Mutations in TCIRG1, OSTM1, ClCN7, and TNFRSF11A genes were detected in nine, three, one, and one patients, respectively. Six patients remain genetically undefined. OSTM1 and ClCN7 mutations were associated with poor neurologic outcome. Among nine patients with TCIRG1 defects, six presented with hypogammaglobulinemia, and one showed primary pulmonary hypertension. Fourteen patients received hematopoietic cell transplantation; of these, nine are alive and eight of them have evidence of osteoclast function. These data may provide a basis for informed decisions regarding the care of patients with IMO. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Trichothiodystrophy-like Hair Abnormalities in a Child with Keratitis Ichthyosis Deafness SyndromePEDIATRIC DERMATOLOGY, Issue 4 2008L. De Raeve M.D., Ph.D. It appears to be genetically heterogeneous and may be caused by mutations in the connexin 26 (Cx26) gene (GJB2) or in the connexin 30 gene. It is characterized by the association of ichthyosis-like skin lesions, hearing loss, and vascularizing keratitis. We report the clinical and molecular findings in a 5-year-old girl with keratitis ichthyosis deafness syndrome. DNA sequencing in our patient revealed a p.Ser17Phe mutation in GJB2. Besides the typical clinical features of keratitis ichthyosis deafness syndrome, a peculiar intriguing finding not previously described in the literature in this condition was that polarizing light microscopy of the scalp hair in our patient revealed striking bright and dark bands as seen in trichothiodystrophy. Amino acid analysis of the hair sample also disclosed a reduced cysteine index. We emphasize that it would be of great benefit to examine hair shafts in other patients with keratitis ichthyosis deafness syndrome for trichothiodystrophy-like abnormalities. [source] A novel mutation of the ,-globin gene promoter (,102 C>A) and pitfalls in family screeningAMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2007Patricia Aguilar-Martinez We describe a family with ,-thalassemia in which several pitfalls of genetic diagnoses were present. These include coherent family phenotypes with discrepancies in molecular findings because of nonpaternity, and a false ,-globin gene homozygous genotype due to a large deletion in the second locus. These findings underline the difficulties of family genetic studies and the need for tight relationship between professionals involved in laboratory studies and those in-charge of the clinical follow-up and genetic counselling. In this family, we also report a new silent ,-thalassemia mutation, ,102 (C>A), in the distal CACCC box of the ,-globin gene promoter. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Holoprosencephaly and holoprosencephaly-like phenotypes: Review of facial and molecular findings in patients from a craniofacial hospital in Brazil,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010Antonio Richieri-Costa Abstract Here we report on the clinical and genetic data for a large sample of Brazilian patients studied at the Hospital de Reabilitação de Anomalas Craniofaciais,Universidade de São Paulo (HRAC-USP) who presented with either the classic holoprosencephaly or the holoprosencephaly-like (HPE-L) phenotype. The sample included patients without detected mutations in some HPE determinant genes such as SHH, GLI2, SIX3, TGIF, and PTCH, as well as the photographic documentation of the previously reported patients in our Center. The HPE-L phenotype has been also called of HPE "minor forms" or "microforms." The variable phenotype, the challenge of genetic counseling, and the similarities to patients with isolated cleft lip/palate are discussed. © 2010 Wiley-Liss, Inc. [source] Genetic skeletal disorders of the fetus and infant: Pathologic and molecular findings in a series of 41 cases,BIRTH DEFECTS RESEARCH, Issue 10 2009Anastasia E. Konstantinidou Abstract BACKGROUND: Genetic skeletal disorders of the fetus and infant are a large group of genetic disorders, comprising the groups formerly assigned as skeletal dysplasias (osteochondrodysplasias), dysostoses, and malformation syndromes with a skeletal component. Genetic skeletal disorders may be prenatally detected by ultrasonography or result in intrauterine or early postnatal death, constituting one difficult diagnostic field met by the pathologist who performs the perinatal autopsy. METHODS: In this retrospective study, we have gathered radiologic, physical, histopathologic, and molecular data regarding 41 cases of genetic skeletal disorders diagnosed among 1980 fetal and perinatal autopsies over a 10-year period. RESULTS: Our series of cases were classified according to the 2006 Nosology and Classification of Genetic Skeletal Disorders. The overall frequency of genetic skeletal disorders was 1:48 autopsies. The FGFR3 group and osteogenesis imperfecta type 2 were the more frequently encountered disorders. The mean gestational age at autopsy was 21.9 weeks (range, 12,37 weeks). A final diagnosis was obtained in 95% of cases. Genetic skeletal disorders were detected by prenatal ultrasound in 90% of cases, with a correct typing of the disorder achieved in only 34%. Molecular analysis was confirmative in 5 cases. CONCLUSIONS: The central role of the perinatal pathologist in collaboration with specialized services is essential for the correct interpretation of the radiologic, physical, and histopathologic findings, to accurately classify specific types of genetic skeletal disorders and enable genetic counseling. Birth Defects Research (Part A), 2009. © 2009 Wiley-Liss, Inc. [source] Systematics of the Nasa poissoniana group (Loasaceae) from Andean South AmericaBOTANICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 3 2009TILO HENNING The monophyletic Nasa poissoniana group (Loasaceae, subfamily Loasoideae) is revised on the basis of extensive field studies, observations in cultivation and the revision of herbarium specimens. A core of taxa has been considered as closely allied on the basis of morphology in the past, but several additional taxa have been recognized as allied to this group on the basis of molecular data. One species, N. raimondii, formerly placed in the N. stuebeliana group, is now transferred to the N. poissoniana complex as a result of the molecular findings. Nasa poissoniana ssp. glandulifera is described as new to science on the basis of morphologically divergent collections of N. poissoniana from two northern departments of Peru. Numerous new localities, often far from the previously known distribution area, are reported for several species. The N. poissoniana group has its centre of diversity in the inner Andean valleys of southern Peru, quite unlike all other groups of Nasa, with centres of diversity in the Amotape,Huancabamba Zone in northern Peru and southern Ecuador. Descriptions, drawings and a distribution map and key to all taxa are provided, and detailed information on habitat and distribution is given for each species. © 2009 The Linnean Society of London, Botanical Journal of the Linnean Society, 2009, 161, 278,301. [source] Chromosome 22q Deletions in Atypical Teratoid/Rhabdoid Tumors in AdultsBRAIN PATHOLOGY, Issue 1 2005Jack Raisanen MD Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, malignant brain tumors that usually occur in the posterior fossa. Both AT/RT and the analogous tumor outside the brain, malignant rhabdoid tumor, share a polyphenotypic immunoprofile and frequent 22q deletions with inactivation of the INI1/hSNF5 gene. Reports, so far, indicate that AT/RTs occur almost exclusively in children, most of whom are 5-years-old or less. The rarity of the tumor and the polyphenotypic immunoprofile, characterized by antigen expression that is often patchy, make diagnosis in adults difficult and controversial. We describe three AT/RTs in adults in which the diagnoses were supported by detection of 22q11.2 deletions, INI1 mutation and/or loss of INI1 protein expression. Two patients were female, ages 20 and 31 and one was male, age 45. Two tumors occurred in the sella or sellar region and one in the cerebellum. In all cases, fluorescence in situ hybridization with probes to the BCR (22q11.2) and NF2 (22q12) regions of chromosome 22 revealed single copy deletions of BCR with normal dosages of NF2 and, in all cases, immunohistochemistry demonstrated loss of INI1 protein expression. In one case, a single base pair deletion was detected in the INI1/hSNF5 gene. These molecular findings confirm the occurrence of AT/RTs in adults. Although rare, AT/RT should be considered in the differential diagnosis of poorly differentiated intracranial tumors in adults. [source] Neutrophilic-chronic myeloid leukemiaCANCER, Issue 9 2002Low levels of p230 BCR/ABL mRNA, undetectable p230 BCR/ABL protein may predict an indolent course Abstract BACKGROUND Neutrophilic-chronic myeloid leukemia (CML-N) has been described as a CML variant associated both with a distinctive molecular defect of the Philadelphia chromosome and with a more benign clinical course than classic CML. The translocation (9;22) in CML-N results in the transcription of an e19/a2 type BCR/ABL mRNA that codes for a 230-kD BCR/ABL protein (p230). The indolence of the clinical course of patients with CML-N has been disputed. METHODS The objectives of this study were to quantify and correlate with clinical outcome the p230 mRNA and protein in patients with CML-N, to describe six new patients and the follow-up (with molecular analysis) of five previously reported patients with CML-N, and to review characteristics of all patients with CML-N and p230 BCR/ABL reported to date in the literature. RESULTS Quantitative polymerase chain reaction assays on specimens from the great majority of patients with CML-N revealed minimal numbers of molecules of p230 BCR/ABL transcripts per total RNA. This also was associated with a lack of detectable p230 BCR/ABL protein in patient specimens, even in one patient who was followed for 16 years after diagnosis. This may explain the milder leukemic phenotype in most patients with CML-N. A review of all 23 patients who had an e19/a2 type BCR/ABL translocation suggested that the low level of p230 BCR/ABL mRNA and the lack of detectable p230 BCR/ABL protein in patients with no additional cytogenetic abnormalities may predict their indolent clinical course. CONCLUSIONS Patients with p230 positive CML-N have indolent course, probably as a result of low p230 mRNA and protein levels. This supports the need to conduct additional molecular studies, even if cytogenetic studies have revealed t(9;22), because of the prognostic importance of the molecular findings. Cancer 2002;94:2416,25. © 2002 American Cancer Society. DOI 10.1002/cncr.10490 [source] New insights in congenital bowing of the femoraCLINICAL GENETICS, Issue 3 2004V Cormier-Daire The aim of this study is to review the clinical, radiological and molecular findings of the bent bone dysplasia group including Stüve-Wiedemann syndrome due to LIFR mutations, Compomelic dysplasia due to SOX9 mutations and Kyphomelic dysplasia with no known molecular bases. [source] | |||||||||||||