PubMed Health⌕ Search

Biomedical subjects

J C Marini

Publications and source records attributed to J C Marini.

67 records · Page 4Linked to original sources
PubMed1988

Human and chick alpha 2(I) collagen mRNA: comparison of the 5' end in osteoblasts and fibroblasts.

Type I collagen, a heterotrimer of two alpha 1(I) chains and one alpha 2(I) chain, is the major structural protein of bone, skin, and tendon. The collagen of patients with bone diseases has been studied in skin fibroblasts instead of osteoblasts because the genes for type I collagen are single-copy genes. While these studies should detect structural changes in the gene, they might fail to detect defects in processes which are dependent on tissue-specific expression. The studies reported here sought to determine whether the expression of type I collagen in skin and bone was characterized by the use of alternate promoters or alternative splicing in the N-propeptide region. Primer extension and nuclease S1 protection experiments were used to analyze the structure of the alpha 2(I) mRNA from the 5' end of the gene through the N-telopeptide coding region (exons 1-6) in human and chick osteoblasts and fibroblasts. The protection and primer extension experiments using human and chick mRNA demonstrated identical routes of splicing in skin and bone at the first five splice junctions. These studies provide reassurance that information obtained from the study of type I collagen in fibroblasts may be extrapolated to bone.

Animals↗
PubMed1988

Dense metaphyseal bands and growth arrest associated with isotretinoin therapy.

A 9-year-old boy, treated with high-dose isotretinoin therapy for fibrodysplasia ossificans progressiva, developed dense metaphyseal bands and growth arrest. Discontinuance of isotretinoin therapy was followed by gradual decrease of metaphyseal bands and resumption of clinical growth. The dense metaphyseal bands may be related to the known action of retinoids as modulators of chondrocyte phenotype and gene expression.

Adolescent↗
PubMed1984

Physical characterization of a kinetoplast DNA fragment with unusual properties.

A 414-base pair fragment from a Leishmania tarentolae kinetoplast DNA minicircle has unusual physical properties. We reported previously that in comparison to phi X174 and pBR322 control fragments, the kinetoplast fragment behaves in gel electrophoresis, gel filtration, and electric dichroism experiments as if it has an unusually compact conformation. We accounted for these unusual properties by proposing that the fragment is a systematically bent helix (Marini, J.C., Levene, S.D., Crothers, D.M., and Englund, P.T. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 7664-7668). In this paper, we further explore the properties of the kinetoplast fragment. Because of its compact conformation, the kinetoplast fragment has difficulty in snaking through polyacrylamide gels and therefore migrates unusually slowly in electrophoresis experiments. Warming (53 degrees C) and ethanol (5-20%) partially normalize gel migration; glyoxal treatment results in denatured strands with electrophoretic mobility close to that expected for their size. In vivo modification does not appear to be responsible for the fragment's properties; its anomalous electrophoretic behavior persists after proteinase K treatment, phenol extraction, or after cloning into pBR322 and reisolation. Velocity sedimentation experiments rule out fragment aggregation. Secondary structure, such as a cruciform, is not detectable by S1 or mung bean nuclease digestion. The kinetoplast fragment has circular dichroism spectra characteristic of a B-type helix. With increasing temperature, there is an increase in the 270/280 ellipticity ratio. Circular dichroism spectra taken in the presence of ethanol show a B to A helix transition at unusually low ethanol concentrations (between 44 and 54% (w/w]. Thermal denaturation reveals a triphasic melting curve.

Animals↗
PubMed1984

Presence of a bent helix in fragments of kinetoplast DNA minicircles from several trypanosomatid species.

Some restriction fragments of kinetoplast minicircles from several trypanosomatid species (Leishmania tarentolae, Trypanosoma brucei, T. equiperdum, Herpetomonas muscarum, Crithidia fasciculata, but not T. cruzi) migrate anomalously on polyacrylamide gels. This behavior is probably due to a natural curvature of the helix. Bent helices appear to be a common property of kinetoplast minicircles, and may be important for minicircle function. In the case of T. equiperdum, we present evidence that each minicircle has a single bent region which resides in or near the 'conserved sequence.'

Animals↗
PubMed1982

Bent helical structure in kinetoplast DNA.

We have investigated the unusual physical properties of a restriction fragment of Leishmania tarentolae kinetoplast DNA. A gel-purified fragment comprising slightly more than half of a minicircle was determined by Maxam-Gilbert sequence determination to be 490 base pairs (bp) in length. This fragment has dramatically anomalous electrophoretic behavior; it has an apparent size of 450 bp on a 1% agarose gel but migrates as 1,380 bp on a 12% polyacrylamide gel. However, in gel filtration on Sephacryl S-500, the fragment elutes with an apparent size of 375 bp. Finally, it behaves anomalously in electric dichroism experiments. Field-free rotational relaxation times from transient electric dichroism studies are highly sensitive to effective molecular dimensions. The rotational relaxation time of the kinetoplast fragment is smaller than that of a 309-bp control fragment from pBR322. Because rigorous control experiments rule out the possibility that this fragment is modified, these anomalous properties must be dictated by the sequence itself. Fragment behavior indicates that it has an unusually compact configuration; we propose that this molecule contains a region of systematically bent B-DNA. This model accounts for the fragment's difficulty in snaking through the pores of a polyacrylamide gel, its ease in diffusing into Sephacryl beads, and its smaller rotational relaxation time. Bending of this molecule may be caused by periodicities in the DNA sequence.

Journal Article↗
PubMed1980

Decatenation of kinetoplast DNA by topoisomerases.

Kinetoplast DNA is the mitochondrial DNA of trypanosomatids such as Crithidia fasciculata. This DNA is in the form of networks containing thousands of DNA circles which are apparently catenated (interlocked). Some topoisomerases, such as T4 phage topoisomerase and DNA gyrase, catalyze a decatenation of the networks to form individual covalently closed circles.

Animals↗
PubMed1980

The replication of kinetoplast DNA.

Kinetoplast DNA is the mitochondrial DNA of trypanosomatids. This DNA consists primarily of thousands of small minicircles which are linked together to form a giant network. Replication of this DNA involves release of individual minicircles from the network to form free minicircles. The free minicircles then replicate and the two progeny are reattached to the network. When all minicircles within the network have replicated, the double-sized network divides to form two progeny structures which are each identical to the parent network.

Animals↗
PubMedDate not supplied

Osteogenesis imperfecta: prospects for molecular therapeutics.

Osteogenesis Imperfecta (OI) is a dominant negative disorder of connective tissue. OI patients present with bone fragility and skeletal deformity within a broad phenotypic range. Defects in the COL1A1 or COL1A2 genes, coding, respectively, for the alpha1 and alpha2 chains of type I collagen, are the causative mutations. Over 150 mutations have been characterized. Both quantitative defects, such as null COL1A1 alleles, and qualitative defects, such as glycine substitutions, exon skipping, deletions, and insertions, have been described in type I collagen. Quantitative and structural mutations are associated with the milder and more severe forms of OI, respectively. A more detailed relationship between genotype and phenotype is still incompletely understood; several models have been proposed and are being tested. Transgenic and knock-out murine models for OI have previously been created. We have recently generated a knock-in murine model (the Brittle mouse) carrying a typical glycine substitution in type I collagen. This mouse will permit a better understanding of OI pathophysiology and phenotypic variability. It will also be used for gene therapeutic approaches to OI, especially mutation suppression by hammerhead ribozymes. The present review will provide an update of OI clinical and molecular data and outline gene therapeutic approaches being tested on OI murine models for this disorder.

Alleles↗