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At least 883 records · Page 49Linked to original sources
PubMed1983

A cytomegalovirus DNA sequence containing tracts of tandemly repeated CA dinucleotides hybridizes to highly repetitive dispersed elements in mammalian cell genomes.

A single 880-base-pair region within the genome of simian cytomegalovirus strain Colburn contains sequences that hybridize intensely with both human and mouse total genome DNA probes. This sequence was also found in a second simian cytomegalovirus isolate and was retained in both plaque-purified virus subclones and in plasmid DNA clones containing the SalI P fragment. Cleaved genomic DNAs from several mammalian species all exhibited strong dispersed hybridization with the SalI-P probes, and over 70% of the lambda clones in a mouse genomic library plus several selected clones containing globin, 45S rDNA, or 5S rDNA genes all formed hybrids with SalI-P. The appropriate region of cytomegalovirus SalI-P contains relatively A + T-rich unique sequences interrupted by three stretches of the simple alternating dinucleotides, (CA)15, (CA)22, and (CA)21, which we show to be responsible for most of the cell-virus homology. We conclude that discrete, tandemly repeated (CA) dinucleotide tracts capable of forming left-handed Z-DNA helices punctuate mammalian genomes at greater than 10(5) copies per cell and that three adjacent copies of what appear to be a family of interspersed repetitive elements containing these (CA)n stretches are carried in the genomes of simian cytomegaloviruses.

Animals↗
PubMed1988

Structure of the human hemopexin gene and evidence for intron-mediated evolution.

The human hemopexin gene was isolated and its structure determined. The gene spans approximately 12 kb and is interrupted by nine introns. When the intron/exon pattern was examined with respect to the polypeptide segments they encode, a direct correspondence between exons and the 10 repeating units in the protein was observed. The introns are not randomly placed; they fall in the middle of the region of amino acid sequence homology in strikingly similar locations in 6 of the 10 units and in a symmetrical position in the two halves of the coding sequence. These features strongly support the hypothesis that the gene evolved through intron-mediated duplications of a primordial sequence to a five-exon cluster. A more recent gene duplication led to the present-day gene organization.

Amino Acid Sequence↗
PubMedDate not supplied

Vincristine neurotoxicity. Pathophysiology and management.

Vincristine is an antineoplastic drug with a broad spectrum of activity against haematological malignancies and childhood sarcomas. Besides useful activity, it lacks the usual emetic and myelotoxicity of anticancer drugs, but its use is limited by neurotoxicity. The neurotoxicity commonly manifests as reduced motility of the intestines resulting in constipation, and peripheral neuropathy which is predominantly sensory in nature. The early symptoms include numbness and tingling of hands and feet which is accompanied by loss of deep tendon reflexes. In its more severe form, muscle weakness develops which is more marked in distal muscles of the hands and feet. Other manifestations of neurotoxicity include ocular palsies, hoarseness of voice, and autonomic neuropathy in the form of postural hypotension and atony of the urinary bladder. The neurotoxicity is dose related and cumulative with repeated dosage such that the drug therapy has to be stopped after a cumulative dose of 30 to 50 mg. The neurotoxicity is usually reversible on interruption of the therapy, but the recovery is slow and takes several months. There are no specific antidotes which have established usefulness against neurotoxicity.

Humans↗
PubMed1997

A phase II trial of all-trans-retinoic acid in hormone-refractory prostate cancer: a clinical trial with detailed pharmacokinetic analysis.

Retinoids have been shown to have substantial anticancer activity in a number of preclinical and clinical situations. There are considerable epidemiologic, in vitro and in vivo data which indicate that retinoids may have a role in the prevention and therapy of human prostate cancer. Based on anecdotal evidence of response in one patient with hormone-refractory prostate cancer (HRPC), we conducted a phase II trial in HRPC during which we also examined changes in pharmacokinetics of all-trans-retinoic acid (ATRA) which occurred during therapy. Enrolled in the study were 17 patients with HRPC who received 50 mg/m2 ATRA three times daily orally on days 1-14, repeated every 22 days. The pharmacokinetics of ATRA were assessed with the first dose on day 1, again on day 14 and after a 7-day interruption in ATRA therapy on day 22. Patients were evaluable for response if they completed two 14-day courses of ATRA; among 13 such patients no responses were seen. Four patients were considered unevaluable for response owing to rapid disease progression in three and intercurrent illness in one. Apparent clearance of ATRA changed substantially during therapy: day 1 3779 +/- 4215 ml/min, day 14 7179 +/- 3197 ml/min, day 22 3213 +/- 2357 ml/min. Area under the curve was proportionately diminished on day 14 compared with day 1 and had returned to baseline by day 22. We conclude that ATRA is not active in HRPC. Failure of this agent in HRPC may be related to failure of drug delivery associated with enhanced mechanisms of ATRA clearance which occur within a few days of beginning ATRA treatment.

Adult↗
PubMed2003

MAX, a novel retrotransposon of the BEL-Pao family, is nested within the Bari1 cluster at the heterochromatic h39 region of chromosome 2 in Drosophila melanogaster.

A homogeneous array of 80 tandem repeats of the Bari1 transposon is located in the pericentromeric h39 region of chromosome 2 of Drosophila melanogaster. Here, we report that the Bari1 cluster is interrupted by an 8556-bp insertion. DNA sequencing and database searches identified this insertion as a previously unannotated retrotransposon that we have named MAX. MAX possesses two ORFs; ORF1 putatively encodes a polyprotein comprising GAG and RT domains, while ORF2 could encode a 288-amino acid protein of unknown function. Alignment with the RT domains of known LTR retrotransposons shows that MAX belongs to the BEL-Pao family, which remarkable for its widespread presence in different taxa, including lower chordates. We have analyzed the distribution of MAX elements within representative species of the Sophophora subgroup and found that they are restricted to the species of the melanogaster complex, where they are heavily represented in the heterochromatin of all autosomes and on the Y chromosome.

Amino Acid Sequence↗
PubMed1996

Deletion during recombination in bacteriophage T7.

The ligase gene of bacteriophage T7 was interrupted with inserts made from synthetic DNA. A pair of inserts were designed so that each insert contained one copy of an identical 17 bp sequence (repeat) positioned such that intermolecular recombination between the 17 bp homologies on separate genomes could delete enough of the insert to produce a functional ligase gene. The frequency of deletion by intermolecular recombination was compared to deletion frequency when repeated copies of the identical 17 bp sequence were present on the same genome separated by 39 bp. When the 17 bp homologous sequences were on different genomes the formation of ligase positive phage was about 7% to 13% of the deletion frequency measured with both repeats on the same genome. A second set of inserts contained the same 17 bp sequence present in the first pair of inserts. The sequence of this second set of inserts was such that when both 17 bp repeats were present on the same genome there was no separation between the repeats. With the second set of inserts (no separation) deletion by intermolecular recombination was about two orders of magnitude higher than what was measured with the first set of inserts where 39 bp of nonhomologous sequence intervened between the 17 bp repeats and the normal T7 genome. These data are interpreted to suggest that in T7 misalignment between repeated sequences during intermolecular recombination may play a role in deletion mutagenesis.

Bacteriophage T7↗
PubMed1989

A LINE 1 sequence interrupts the rat alpha 2u globulin gene.

The rat alpha 2u globulin gene family is composed of about 25 members with closely related structure. Several of these genes are transcriptionally active in the liver of adult males. We isolated about 50 independent genomic clones from the library and determined complete nucleotide sequences of two. Although they were alike and revealed structural features prerequisite for active genes, one cloned gene was interrupted in the 6th intron with about 900 bp 5' truncated and 3'-terminal triplicated form of LINE 1 sequence flanked by 16 bp complete direct repeat originating from the 6th intron. Within the inserted LINE 1 an excellent splicing acceptor homologue with a precedent lariat junction motif and multiple polyadenylation signals was identified. Thus, the possible production of a chimeric RNA, the last exon of which would be replaced by a part of LINE 1, has to be considered.

Alpha-Globulins↗
PubMed1987

The first-step transfer-DNA injection-stop signal of bacteriophage T5.

Bacteriophage T5 is different from most phages in that its DNA is injected in two steps during infection. The region containing the injection stop signal (iss) has been cloned and sequenced and found to contain numerous large repeats and inverted repeats which may be part of the iss. The most impressive of these are the 31-bp repeat units (rb) which are present three times in 99 bp. The rb repeats, themselves, contain inverted repeats so that mutually exclusive stem-and-loop structures may potentially form, not only within the repeats, but also between them. Another pair of repeats (21 bp each) contains two sequences resembling DnaA protein-binding sites. The region sequenced also contains one of the T5 site-specific strand interruptions and this was found to lie at the base of a perfect 9-bp palindrome.

Base Composition↗
PubMed1988

The ethanol regulon in Aspergillus nidulans: characterization and sequence of the positive regulatory gene alcR.

The regulatory gene, alcR, of Aspergillus nidulans, encodes a protein that induces the expression of the alcA and aldA genes. The alcR gene is inducible, autoregulated, and subject to carbon catabolite repression. We report the complete nucleotide sequence of the alcR gene and its 5' and 3' non-coding regions. In the 5' flanking region of the alcR gene, several repeats and inverted repeats were found, and small sequence similarities were also found with the 5' flanking regions of the alcA and aldA genes. One intron of small size interrupts the open reading frame. The start point of transcription was mapped 50 nucleotides upstream from the putative start codon, and a sequence CAATG was found 5' to the polyadenylation site of the transcript that could play a role in selection of the polyadenylation site. The putative alcR-encoded protein was identified in vivo as an inducible polypeptide of 96 kDa in a transformant carrying multiple copies of the alcR gene.

Alcohol Dehydrogenase↗
PubMed1993

Cloning and sequence analysis of an H(+)-ATPase-encoding gene from the human dimorphic pathogen Histoplasma capsulatum.

A gene related to the PMA1 gene from Saccharomyces cerevisiae was isolated from the pathogenic human dimorphic fungus, Histoplasma capsulatum, using fungal-specific oligodeoxyribonucleotide (oligo) probes. This gene has been given the name Hc-PMA1. The structural organization of Hc-PMA1 consists of three exons (375, 2329 and 44 bp) and two introns (115 and 116 bp). The nucleotide sequence predicts an H(+)-ATPase-related protein of 916 amino acids (aa). Comparison of the deduced aa sequence to that of Neurospora crassa and S. cerevisiae (PMA1) plasma membrane H(+)-ATPases showed a greater similarity to that from N. crassa (85% identity). Furthermore, the two introns in the Hc-PMA1 gene interrupt the coding region in the precise locations determined for two of the four N. crassa Nc-PMA introns. H. capsulatum intron 1 contains two repeat motifs, d(TA)16 and d(TG)10, each potentially capable of forming non-B DNA structures. Northern analysis of H. capsulatum total RNA indicated that the Hc-PMA1-specific mRNA is approx. 3.3 kb in size, in agreement with the predicted size of the gene.

Amino Acid Sequence↗
PubMed1996

Isolation and characterization of two novel genes expressed in germinating conidia of the obligate biotroph Erysiphe graminis f.sp. hordei.

A cDNA library was constructed from germinating conidia of the obligate biotrophic fungus, Erysiphe graminis DC ex Mérat f.sp. hordei Em. Marchal (Egh). Subtractive hybridization and differential screening were carried out. Two cDNA clones, cEgh7 and cEgh16, which were highly expressed in germinating conidia, but not in ungerminated conidia, were selected for further characterization. The corresponding genomic sequences, gEgh7 and gEgh16, were isolated from a cosmid library and sequenced. The gEgh7 gene contains an open reading frame (ORF) that codes for a 249-amino-acid (aa), Pro-rich polypeptide with a repeated primary structure. Expression studies in planta indicated that gEgh7 may have a function in the development and maturation of conidia. The ORF of gEgh16 is interrupted by two introns of 91 and 119 bp. It encodes a 251-aa polypeptide of unknown function. This gene belongs to a multigene family and is expressed during all developmental stages of Egh in planta and may be associated with hyphal growth.

Amino Acid Sequence↗
PubMed2003

The impact of chemotherapy on morbidity due to schistosomiasis.

Current knowledge on the impact of chemotherapy on schistosomiasis-related morbidity is still fragmentary. In urinary schistosomiasis, reversal of organ pathology follows cure after 6 months and resurgence takes place after at least another 6 months. Retreatment after less than 1 year is, therefore, unnecessary. Also, intestinal schistosomiasis appears to regress promptly after chemotherapy. For the reversal of hepatic morbidity, more than one chemotherapy round appears necessary at least in foci of intense transmission of schistosomiasis. The earlier chemotherapy is given, the higher the chances of reversal of schistosomal pathology, but pathology may regress to some extent also in adults. The regression and resurgence of periportal fibrosis, as detected by ultrasonography, occurs with a delay of 7 months to more than 2 years after therapy. Retreatment after less than 1 year may not permit full assessment of the impact of the first round on hepatic morbidity. Children and adolescents should be the major target population, taking into account that in many foci, children out-of-school must be covered because they are at the highest risk. Repeated treatment during childhood may prevent the development of urinary tract disease in adulthood. However, no data are available on the prevention of genital pathology. Repeated chemotherapy may have a long term effect on re-infection intensities and the development of severe morbidity, even in foci where control has been interrupted for many years. Severe hepatic fibrosis may be prevented even in foci of intense transmission provided more than two rounds of chemotherapy have been given in childhood and that chemotherapy is available on demand. Chemotherapy has an important impact on child development, physical fitness and working capacity. Its effect on growth and anemia is improved by simultaneous treatment of intestinal parasites and the provision of adequate iron supplementation. The impact of chemotherapy on many of the multifaceted manifestations of schistosomiasis has not been assessed systematically. More data are needed on gallbladder pathology, neuroschistosomiasis, endocrinologic disorders, bladder cancer and co-infections with other pathogens. In areas where control has been achieved, the overall morbidity and mortality has decreased with a delay of many years or even decades.

Animals↗
PubMed1979

Intramuscular 16-phenoxy PGE2 ester for pregnancy termination.

A new PGE2 derivative (16-phenoxy PGE2 methyl sulfonylamide sulprostone) was administered by the i.m. route to 48 women pregnancy in any of the three trimesters. The indications for pregnancy interruption were either serious medical problems in intact pregnancies (21 cases) or due to fetal death in utero (27 cases). Single doses of 500 micrograms were repeated every 4 hours in the former group or every 6 hours in the latter category for a maximum period of 24 hours. The treatment was successful in 81% of intact pregnancies and in 92.6% of fetal death cases with an overall mean induction interval of 12.9 hours. More than half the subjects did not experience any side effects apart from mild or moderate uterine colics. An overall mean of 1.4 episodes of vomiting or diarrhoea per induction trial was quite acceptable from the clinical point of view. The absence of serious complications in the group of critically sick women speaks in favor of the relative safety of the drug.

Abortifacient Agents↗
PubMed2000

An efficient method for dispersing Ds elements in the barley genome as a tool for determining gene function.

To devise a method for function-based gene isolation and characterization in barley, we created a plasmid containing the maize Activator (Ac) transposase (AcTPase) gene and a negative selection gene, codA, and a plasmid containing Dissociation (Ds) inverted-repeat ends surrounding the selectable herbicide resistance gene, bar. These plasmids were used to stably transform barley (Hordeum vulgare). In vitro assays, utilizing a Ds-interrupted uidA reporter gene, were used to demonstrate high-frequency excisions of Ds when the uidA construct was introduced transiently into stably transformed, AcTPase-expressing plant tissue. Crosses were made between stably transformed plants expressing functional transposase under the transcriptional control of either the putative AcTPase promoter or the promoter and first intron from the maize ubiquitin (Ubi1) gene, and plants containing Ds-Ubi-bar. In F(1) plants from these crosses, low somatic and germinal transposition frequencies were observed; however, in F(2) progeny derived from individual selfed F(1) plants, up to 47% of the plants showed evidence of Ds transposition. Further analyses of F(3) plants showed that approximately 75% of the transposed Ds elements reinserted into linked locations and 25% into unlinked locations. Transposed Ds elements in plants lacking the AcTPase transposase gene could be reactivated by reintroducing the transposase gene through classical genetic crossing, making this system functional for targeted gene tagging and studies of gene function. During the analysis of F(3) plants we observed two mutant phenotypes in which the transposed Ds elements co-segregate with the new phenotype, suggesting the additional utility of such a system for tagging genes.

Chromosome Segregation↗
PubMed1996

A model for testing recombinogenic sequences in the mouse germline.

Homologous recombination is a conserved process of genetic exchange generated by homologous pairing of nucleotides. Species diversity and gene evolution are dependent on the outcomes of recombination during germ cell development, yet systems to study mammalian germline recombination, especially those with applications to human genetics, are not well developed. We report on a transgenic mouse system designed to study recombination within test sequences in the male germline utilizing an intron-interrupted lacZ reporter gene. beta-galactosidase positive sperm are detected and quantitated by flow cytometry using fluorogenic substrates. Examination of recombination within a 1.7 kb repeat of test sequences derived from the human glycophorin breakpoint cluster region detects approximately 0.04-0.09% fluorescent sperm. Confirmation that these sperm result from recombination in the germline comes from histochemical staining of testicular cells, examination of spliced mRNA, and PCR analysis of sorted sperm populations. The system is readily adaptable to studies of other sequences reported to have elevated levels of recombination, including those implicated in human genetic disease. Investigations of the molecular basis for genomic instability at specific chromosomal locations may yield important insights into mechanisms of chromosomal loss and rearrangements.

Animals↗
PubMed1996

Cloning and analysis of the genes encoding the type IIS restriction-modification system HphI from Haemophilus parahaemolyticus.

The genomic region encoding the type IIS restriction-modification (R-M) system HphI (enzymes recognizing the asymmetric sequence 5'-GGTGA-3'/5'-TCACC-3') from Haemophilus parahaemolyticus were cloned into Escherichia coli and sequenced. Sequence analysis of the R-M HphI system revealed three adjacent genes aligned in the same orientation: a cytosine 5 methyltransferase (gene hphIMC), an adenine N6 methyltransferase (hphIMA) and the HphI restriction endonuclease (gene hphIR). Either methyltransferase is capable of protecting plasmid DNA in vivo against the action of the cognate restriction endonuclease. hphIMA methylation renders plasmid DNA resistant to R.Hindill at overlapping sites, suggesting that the adenine methyltransferase modifies the 3'-terminal A residue on the GGTGA strand. Strong homology was found between the N-terminal part of the m6A methyltransferasease and an unidentified reading frame interrupted by an incomplete gaIE gene of Neisseria meningitidis. The HphI R-M genes are flanked by a copy of a 56 bp direct nucleotide repeat on each side. Similar sequences have also been identified in the non-coding regions of H.influenzae Rd DNA. Possible involvement of the repeat sequences in the mobility of the HphI R-M system is discussed.

Amino Acid Sequence↗
PubMed1990

Long insertions within telomeres contribute to chromosome size polymorphism in Plasmodium berghei.

During prolonged in vivo mitotic multiplication of a Plasmodium berghei ANKA clone (8417HP), parasites that contained an enlarged version of chromosome 4 were observed. Restriction mapping and hybridization results demonstrated that the extra DNA present in the enlarged chromosome consists of 2.3-kb tandem repeats, known to be normally located in subtelomeric position at several chromosomal ends but absent in the original chromosome. The inserted 2.3-kb units appeared to interrupt one of the original telomeres and to create an internal (approximately 1-kb-long) telomeric sequence.

Animals↗
PubMed2000

Reperfusion injury pathophysiology in sickle transgenic mice.

Reperfusion of tissues after interruption of their vascular supply causes free-radical generation that leads to tissue damage, a scenario referred to as "reperfusion injury." Because sickle disease involves repeated transient ischemic episodes, we sought evidence for excessive free-radical generation in sickle transgenic mice. Compared with normal mice, sickle mice at ambient air had a higher ethane excretion (marker of lipid peroxidation) and greater conversion of salicylic acid to 2,3-dihydroxybenzoic acid (marker of hydroxyl radical generation). During hypoxia (11% O(2)), only sickle mice converted tissue xanthine dehydrogenase to oxidase. Only the sickle mice exhibited a further increase in ethane excretion during restitution of normal oxygen tension after 2 hours of hypoxia. Only the sickle mice showed abnormal activation of nuclear factor-kappaB after exposure to hypoxia-reoxygenation. Allopurinol, a potential therapeutic agent, decreased ethane excretion in the sickle mice. Thus, sickle transgenic mice exhibit biochemical footprints consistent with excessive free-radical generation even at ambient air and following a transient induction of enhanced sickling. We suggest that reperfusion injury physiology may contribute to the evolution of the chronic organ damage characteristic of sickle cell disease. If so, novel therapeutic approaches might be of value.

Allopurinol↗