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At least 1,045 records · Page 58Linked to original sources
PubMed1993

Cloning and comparative mapping of a human chromosome 4-specific alpha satellite DNA sequence.

We have isolated and characterized two human alphoid DNA clones: p4n1/4 and pZ4.1. Clone p4n1/4 identifies specifically the centromeric region of chromosome 4; pZ4.1 recognizes a subset of alphoid DNA shared by chromosomes 4 and 9. The specificity was determined using fluorescence in situ hybridization experiments on metaphase spreads and Southern blotting analysis of human-hamster somatic cell hybrids. The genomic organization of both subsets was also investigated. Comparative mapping on chimpanzee and gorilla chromosomes was performed. p4n1/4 hybridizes to chimpanzee chromosomes 11 and 13, homologs of human chromosomes 9 and 2q, respectively. On gorilla metaphase spreads, p4n1/4 hybridizes exclusively to the centromeric region of chromosome 19, partially homologous to human chromosome 17. No hybridization signal was detected on chromosome 3 of both chimpanzee and gorilla, in both species homolog of human chromosome 4. Identical comparative mapping results were obtained using pZ4.1 probe, although the latter recognizes an alphoid subset distinct from the one recognized by p4n1/4. The implications of these results in the evolution of centromeric regions of primate chromosomes are discussed.

Animals↗
PubMed1998

Analysis of hapten binding and catalytic determinants in a family of catalytic antibodies.

We report here the cloning and kinetic analysis of a family of catalytic antibodies raised against a common transition state (TS) analog hapten, which accelerate a unimolecular oxy-Cope rearrangement. Sequence analysis revealed close homologies among the heavy chains of the catalytically active members of this set of antibodies, which derive mainly from a single germline gene, whereas the light chains can be traced back to several different, but related germline genes. The requirements for hapten binding and catalytic activity were determined by the construction of hybrid antibodies. Characterization of the latter antibodies again indicates a strong conservation of binding site structure among the catalytically active clones. The heavy chain was found to be the determining factor for catalytic efficiency, while the light chain exerted a smaller modulating effect that depended on light chain gene usage and somatic mutations. Within the heavy chain, the catalytic activity of a clone, but not hapten binding affinity, depended on the sequence of the third complementarity determining region (CDR). No correlation between high affinity for the hapten and high rate enhancement was found in the oxy-Cope system, a result that stands in contrast to the expectations from transition state theory. A mechanistic explanation for this observation is provided based on the three-dimensional crystal structure of the most active antibody, AZ-28, in complex with the hapten. This study demonstrates the utility of catalytic antibodies in examining the relationship between binding energy and catalysis in the evolution of biological catalysis, as well as expanding our understanding of the molecular basis of an immune response.

Amino Acid Sequence↗
PubMed1986

Mapping of haploid expressed genes: genes for both mouse protamines are located on chromosome 16.

Mouse spermatozoa contain two protamines with different amino acid sequences. By hybridizing Southern blots of a series of mouse-hamster somatic cell hybrids containing subsets of mouse chromosomes and a complete set of hamster chromosomes with 32P-labeled cDNAs for each mouse protamine, we assign the two mouse protamine genes to chromosome 16. This report presents the first evidence for chromosomal linkage of two sperm-specific, haploid regulated gene products.

Animals↗
PubMed1991

The mouse homolog of the Gibbon ape leukemia virus receptor: genetic mapping and a possible receptor function in rodents.

The mouse homolog of the Gibbon ape leukemia virus (GALV) receptor (Glvr-1) was mapped to mouse Chromosome 2 (Chr 2) by Southern blot analysis of somatic cell hybrids and positioned on this chromosome using an interspecies genetic cross. Mouse Chr 2 also encodes a receptor (Rec-2) for the wild mouse virus M813. To investigate whether Glvr-1 and Rec-2 could be the same gene, we sought evidence for sequence homology between the env- genes of their respective viruses. Southern blot hybridization with GALV-derived env and pol-env probes failed to detect any homology between GALV and M813, but did show that all mouse species tested carry numerous copies of GALV-related sequences. We speculate that a functional receptor for GALV-related viruses was expressed during Mus evolution.

Animals↗
PubMed1997

DNA methylation and imprinting: why bother?

DNA methylation is crucial for mammalian development because embryos that cannot maintain normal methylation levels die after gastrulation. I propose that DNA methylation is only important for the somatic lineages, but has no role in embryonic lineages including the germ line. Among vertebrates, genomic imprinting is found only in mammals, and numerous hypotheses have ascribed an essential function to imprinting because of the uniquely mammalian developmental and physiological requirements. However, our understanding of molecular details of the imprinting process, as well as evolutionary considerations, is rather consistent with imprinting having no intrinsic role in mammalian development.

Animals↗
PubMed1996

The role of the insulin-like growth factor binding proteins and the IGFBP proteases in modulating IGF action.

Over the past few years, there has been an explosion of data in the scientific literature regarding the various components of the IGF axis. IGFBPs and related molecules are now believed to be critical elements in numerous cellular processes and key factors in several disease states related to abnormal tissue and somatic growth. Recently, the BP-Prs were included in this complex system, and their importance is being unraveled. The upcoming years will undoubtedly bring even more information on the molecular biology of these key cellular regulators. These discoveries are likely to lead to better understanding of growth and cellular regulation and to development of novel therapeutic approaches to a variety of diseases.

Animals↗
PubMed2001

Mutational analysis of TSC1 and TSC2 genes in gangliogliomas.

Gangliogliomas constitute the most frequent tumour entity in patients with temporal lobe epilepsy. The characteristic histopathological admixture of glial and neuronal elements, the focal nature and their differentiated phenotype and benign biological behaviour suggest an origin from a developmentally compromised or dysplastic precursor lesion. The present study analysed TSC1 and TSC2 genes as potential candidates involved in the pathogenesis of this intriguing neoplasm. Recent data suggest that both genes play a role in cortical differentiation and growth control. DNA sequence analysis of TSC1 and TSC2 was studied in 20 patients with gangliogliomas. Fifteen of these tumours (75%) carried polymorphisms in the TSC2 gene. The frequency of these polymorphisms was significantly increased in intron 4 (12.5%) and exon 41 (15%) compared to control individuals (8.1 and 6.5%, respectively, n = 100). A somatic mutation in intron 32 of the TSC2 gene was encountered in one patient. In the TSC1 gene, seven polymorphisms occurred as a combination of base exchanges in exon 14 and intron 13. No mutations were observed in this gene. Laser microdissection and harvesting of individual neuronal and glial elements identified the intron 32 mutation within the glial portion but not in dysplastic neurones of the tumour. The data demonstrate numerous polymorphisms as well as a novel TSC2 mutation in gangliogliomas from patients with chronic epilepsies. The selective detection of the TSC2 mutation within the glial component of a ganglioglioma suggests that the glioma portion has undergone clonal evolution in this case.

Brain Neoplasms↗
PubMed1985

Spontaneous alteration of idiotype in a monoclonal B-cell lymphoma. Escape from detection by anti-idiotype.

The surface immunoglobulin of B-cell neoplasms provides a specific point of attack for potential antibody therapy. The capacity of anti-idiotype antibody to home to the target neoplasm requires that the idiotype be unique and that it be expressed by every cell in the neoplastic clone. We describe the evolution of an altered idiotype in a follicular lymphoma that resulted in escape from laboratory detection by monoclonal anti-idiotype antibody. This was not due to the emergence of a second (biclonal) lymphoma, since all the neoplastic cells were otherwise identical both phenotypically and genotypically, as determined by flow cytometry and genomic DNA (Southern blot) hybridization, respectively. All cells expressed the same B-cell immunotype and bore a constant amount of IgMk. The demonstration of a single configuration of immunoglobulin-gene DNA confirmed monoclonality and established that the change in idiotype was not a result of new gene rearrangements but was more likely due to somatic mutation of the variable region--a process presumed to occur naturally in B cells. These data demonstrate the lability of idiotype expression and define a mechanism by which B-cell neoplasms may become unresponsive to anti-idiotype therapy.

Adult↗
PubMed2004

Transposable elements for transgenesis and insertional mutagenesis in vertebrates: a contemporary review of experimental strategies.

Functional genomic analyses in vertebrate model systems, including fish, frogs, and mice, have greatly contributed to our understanding of embryonic development and human disease. However, new molecular tools and strategies are needed to meet the increasing demands of linking sequence information to gene function. Transposable elements (TEs) are very efficient at integrating into DNA, and are therefore useful vectors for transferring new genetic material into genomes. In particular, members of the Tc1/mariner superfamily of elements are able to transpose in species other than their hosts, and are therefore emerging tools for functional genomics in several organisms. This chapter describes strategies of using retrovirus vectors and DNA-based TEs for transgenesis and insertional mutagenesis in vertebrates, with special emphasis on the Sleeping Beauty (SB) element, a reconstructed Tc1/mariner-like transposon from fish. SB jumps efficiently in cells of diverse vertebrate species in culture, as well as in somatic and germline tissues of the mouse in vivo. Simple structure and easy laboratory handling of transposon vectors are coupled with efficient and stable transgene integration and persistent, long-term transgene expression by transposon-mediated gene transfer. These features all contribute to the usefulness of TEs as tools for vertebrate functional genomics, as well as for animal biotechnology and human gene therapy.

Animals↗
PubMedDate not supplied

[Cephalometric changes in acromegaly].

Acromegaly represents the endocrine disease which includes the somatic and metabolic disorders secondly resulting to the augmentation of the Growth Hormone secretion after the growth cartilages closing (in adult). In this case we can find very important troubles which characterize all the specific elements of the stomatognathic system. The cranio-facial skeleton has a specific configuration, the mandible is developed in excess and the relationships between the maxilla, the mandible and the skull are strongly modified. These and the structural bony troubles, the bony asymmetries involve periodontal, muscular and articular disturbances. In this study we want to describe the craniofacial cephalometric qualitative and quantitative disorders and to emphasize their implications in the onset and the evolution of the stomatognathic system dysfunctional syndrome.

Acromegaly↗
PubMed1989

[Genome mapping in silver fox. Syntenic genes in Carnivora].

Hamster X fox somatic cell hybrids segregating individual fox chromosomes in different combinations were used to assign seven structural loci to fox chromosomes. The gene for ME1 was mapped on the VFU1 chromosome, the genes for ADK and PP being located on the VFU4 chromosome. The gene for GSR was assigned to the VFU7 chromosome and the genes for MPI and COT1 were assigned to the VFU15 chromosome. Localization of these genes enhances the established fox genetic map and extends the known syntenic homologies between the fox and other mammalian. The comparison of data on gene mapping has provided basis for suggestion that there are significant differences in rates of karyotypic evolution in many mammalian taxa.

Animals↗
PubMed2000

Neo-self antigens and the expansion of B-1 cells: lessons from atherosclerosis-prone mice.

The pathogenesis of atherosclerosis involves an inflammatory process that is modulated by the immune system, and within these complex responses we have discerned a possible role for an archetypic B-1 clone. We speculate that due to their immunogenicity and in vivo distribution the "neo"-self determinants created in oxidatively modified LDL are highly stimulatory for certain B-1 cell clones. These neo-self determinants, which can be created chemically, by somatic processes, may in fact represent the molecular analogues of somatic maturation, or even aging. These changes, including those on non-protein antigens induced by oxidative metabolism, amongst others, create neo-determinants against which the host no doubt can not develop rigorous B-cell tolerance. The onset of expression of these oxidative neo-determinants relatively late in development may well serve a useful function for the highly evolved mammalian immune system, as targeting by evolutionarily selected B-1 clones may facilitate the amplification of other useful antibody-mediated physiologic functions. As in the case of the T15 clone, these antibodies may aid in protection against common microbial pathogens. Hence we postulate that during the evolution of the adaptive immune system the neo-self antigenic milieu may have been exploited for the natural selection of primordial clonal specificities. The T15 B-1 clone may then illustrate a common paradigm in which there has been natural selection based on utility for the defense of the individual from environmental threats, as well as for possible "housekeeping" role(s) and the maintenance of cellular homeostasis.

Animals↗
PubMed1993

Localization of a gamma-glutamyl-transferase-related gene family on chromosome 22.

A gene family encompassing a minimum of four genes or pseudogenes for gamma-glutamyl transferase (GGT; EC 2.3.2.2) is present on chromosome 22q11. We have previously isolated a cDNA related to GGT but clearly not belonging to its gene family. The chromosomal location of this related gene, GGTLA1, has been determined by both isotopic and fluorescence in situ hybridization to metaphase cells and by Southern blot analysis of somatic cell hybrid DNAs. We show that GGTLA1 is part of a distinct gene family, which has at least four members (GGTLA1, GGTLA2, GGTLA3, GGTLA4). At least two loci are located on chromosome 22 within band q11 and proximal to the chronic myelogenous leukemia (CML) breakpoint in BCR (breakpoint cluster region gene). At least one other member is located more distally between the breakpoints found in Ewings sarcoma and CML. Some of the GGT and GGTLA family members are located on NotI restriction enzyme fragments of a similar size. Combined results indicate that a segment of human chromosome 22q11 has undergone large-scale amplification events relatively recently in evolution.

Blotting, Southern↗
PubMed1991

Fine structure physical mapping of the region of mouse chromosome 10 homologous to human chromosome 21.

Comparative mapping of human and mouse DNA for regions of genetic homology between human Chromosome 21 and the mouse genome is of interest because of the possibility of developing mouse models of human trisomy 21 (Down syndrome), understanding chromosome evolution, and isolating novel sequences conserved between the two species. At least two mouse chromosomes are known to carry sequences homologous to those on human Chromosome 21: mouse Chromosome 16 (D21S16h, D21S13h, D21S52h, App, Sod-1, Mx-1, Ets-2, Prgs,Ifnar) and mouse Chromosome 17 (D21S56h, Crya-1, and Cbs). Recently, five additional genes have been mapped within region 21q22 of human Chromosome 21:PFKL, CD18, COL6A1, COL6A2, and S100B. To assign these sequences to specific mouse chromosomes, we used human cDNA probes for COL6A1, COL6A2, CD18, and PFKL and a rat brain cDNA probe for S100B in conjunction with a panel of seven Chinese hamster-mouse somatic cell hybrids segregating mouse chromosomes. The specific chromosome complements of the hybrid cell lines and the presence or absence of hybridizing mouse sequences in their DNAs allow us to assign all five sequences to mouse Chromosome 10, with the assignment of Pfkl reported here for the first time. Analysis of genomic mouse DNA fragments produced by digestion with rare-cutting restriction enzymes and separated using pulsed-field gel electrophoresis allows us to construct a fine-structure physical map of two segments of the region of Chromosome 10 containing these five markers. The five loci span at least 1900 kb of mouse DNA and are consistent with the human order: Pfkl-Cd-18-Col6a-1-Col6a-2-S100b.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Female post-reproductive lifespan: a general mammalian trait.

Traditional explanations for the evolution of menopause and post-reproductive lifespan in human females have been based on the benefits of maternal or grand-maternal care outweighing the cost of lost reproduction. These explanations assume an evolutionary origin of menopause since human divergence with the most recent common ancestor. In this study, I conduct a literature survey of studies of 42 mammal species from eight orders, showing that post-reproductive lifespan appears to be widespread among mammals. I then propose an alternative to traditional hypotheses: following accepted theories of trade-offs and senescence, I suggest that the cost of extending reproductive lifespan might be relatively high in female mammals. Somatic and reproductive senescence appear to follow separate trajectories, so it is not surprising that the two processes should occur on different schedules. The timing of each process is probably determined by maximization of reproductive performance and survival early in adulthood, with consequent trajectories resulting in a post-reproductive lifespan. The early end of reproduction relative to lifespan may be due to the cost of production and/or maintenance of oocytes, which decline exponentially over time. Oocyte number below a threshold may trigger an end to normal hormonal cycling.

Aging↗
PubMedDate not supplied

[Multiple sclerosis and depression].

INTRODUCTION: Depression has frequently been reported in multiple sclerosis. However, prevalence rates must be interpreted in the light of the conceptual and methodological limitations of these studies. Depression has traditionally been associated with response to the diagnosis of this disease, the presence of physical and cognitive limitations, the damage of specific neural systems and inmunomodulatory therapy. AIMS: To assess the evolution of emotional state and its relationship with motor and cognitive slowness, in relapsing remitting patients with minimal levels of neurological disability. PATIENTS AND METHODS: Data are reported for 35 patients with relapsing remitting multiple sclerosis, 27 treated with interferons and 8 without interferon treatment. Mood disturbance (Beck Depression Inventory, BDI), physical disability (Kurtzke Expanded Disability Status Scale, EDSS) and speed of information processing (reaction times) were assessed. The first testing was carried out before the start of treatment and the second testing one year later. RESULTS AND CONCLUSIONS: The group of patients showed a total BDI score indicative of minimal depression associated with items expressing performance difficulties and somatic complaints. Emotional state was not related to physical disability but was related to processing speed measures. A significant improvement of depression was observed after one year of treatment with inmunomodulatory therapy.

Adult↗
PubMed1984

Further characterization of the external urethral sphincter in spinal cord injury: study during spinal shock and evolution of responsiveness to alpha-adrenergic stimulation.

To shed further insight into its ever evolving concepts, we studied the activity of the external urethral sphincter in patients with spinal cord injury. Study during the phase of acute spinal shock revealed persistent electromyographic activity in the external urethral sphincter and no activity in the external anal sphincter, suggesting the presence of functional dissociation between the 2 sphincters from the onset of acute spinal injury. The genesis of dissociated activity was discussed by reference to recent experiments on the individual differences in motor neuron and muscle subtypes. Only the external urethral sphincter of chronic paraplegics demonstrated a uniformly increased electromyographic activity after alpha-adrenergic stimulation, while the response in the external anal sphincter was variable. The mechanism of increased response to alpha-adrenergic stimulation in the denervated external urethral sphincter appears to reside either in direct postsynaptic stimulation or recruitment of motor neurons other than the somatic pudendal system, since pre-treatment with competitive muscle relaxant failed to block this increased response in the external urethral sphincter.

Adrenergic Fibers↗
PubMed1996

Testis-specific expression of mRNAs for a unique human type 1 hexokinase lacking the porin-binding domain.

Several enzymes in the glycolytic pathway are reported to have spermatogenic cell-specific isozymes. We reported recently the cloning of cDNAs representing three unique type 1 hexokinase mRNAs (mHk1-sa, mHk1-sb, and mHk1-sc) present only in mouse spermatogenic cells and the patterns of expression of these mRNAs (Mori et al., 1993: Biol Reprod 49:191-203). The mRNAs contain a spermatogenic cell-specific sequence, but lack the sequence for the porin-binding domain that somatic cell hexokinases use to bind to a pore-forming protein in the outer mitochondrial membrane. We now report the cloning of cDNAs representing three unique human type 1 hexokinase mRNAs (hHK1-ta, hHK1-tb, and hHK1-tc) expressed in testis, but not detected by Northern analysis in other human tissues. These mRNAs also contain a testis-specific sequence not present in somatic cell type 1 hexokinase, but lack the sequence for the porin-binding domain. The hHK1-tb and hHK1-tc mRNAs each contain an additional unique sequence. The testis-specific sequence of the human mRNAs is similar to the spermatogenic cell-specific sequence of the mouse mRNAs. Furthermore, Northern analysis of RNA from mouse, hamster, guinea pig, rabbit, ram, human, and rat demonstrated expression of type 1 hexokinase mRNAs lacking the porin-binding domain in the testes of these mammals. These results suggest that hexokinase may have unique structural or functional features in spermatogenic cells and support a model proposed by others for hexokinase gene evolution in mammals.

Amino Acid Sequence↗