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Results for “Chain Migration”

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PubMed1987

Four Ia invariant chain forms derive from a single gene by alternate splicing and alternate initiation of transcription/translation.

We determined the structural basis for the presence of electrophoretically-distinct, antigenically-related forms of invariant chains in Ia oligomers, and established the mechanisms by which they can be expressed from a single gene. S1 nuclease protection assays indicated that, in B cells, transcription of this gene initiates at a minimum of three sites. Thus, unlike previously thought, invariant chain mRNAs have heterogeneous 5' untranslated segments that may differentially affect initiation of translation. Further, restriction mapping and nucleotide sequencing of cDNAs revealed two kinds of invariant chain mRNAs differing by an internal coding segment of 192 bp. This segment represents an alternatively spliced exon, as demonstrated by nucleotide sequencing of corresponding genomic regions. The exon (exon X) encodes a cysteine-rich stretch of 64 amino acids near the COOH terminus that displays a striking and surprising homology to an internal amino acid repeat of thyroglobulin, suggesting an evolutionary mechanism of exon shuffling. Transient expression of cDNAs indicated that both types of alternatively spliced mRNAs contain two in-frame AUGs functioning as alternate start sites for translation. Thus, transfections with exon X-lacking cDNAs resulted in the expression of Mr 33,000 and 31,000 proteins, detected by immunoprecipitation with anti-invariant chain antisera, and identical by two-dimensional gel (2-D) analyses to the B cell invariant-chain forms gamma 1 (Mr 31,000), gamma 2, and gamma 3 (Mr 33,000). Similarly, exon X-containing cDNAs expressed Mr 43,000 and 41,000 proteins, also identical by 2-D migration to Ia-associated proteins. Thus, human Ia molecules contain four forms of invariant chain of closely related but nonidentical primary structure that are generated from a single gene by a complex pattern of alternate transcriptional start, exon splicing, and translational start.

Base Sequence↗

PubMed2005

Muscle fiber differentiation in fish embryos as shown by in situ hybridization of a large repertoire of muscle-specific transcripts.

Skeletal muscles are composed of different fiber types, largely defined by differential expression of protein isoforms involved in myofibrillogenesis or metabolism. To learn more about the gene activations that underlie the differentiation and the diversification of embryonic fish myotomal fibers, we investigated the developmental expression of 25 muscle genes in trout embryos by in situ hybridization of muscle-specific transcripts. The earliest event of muscle differentiation, at approximately the 25-somite stage, was the expression of a variety of muscle-specific genes, including slow-twitch and fast-twitch muscle isoforms. The activation of these muscle genes started in the deep somitic domain, where the slow muscle precursors (the adaxial cells) were initially located, and progressively spread laterally throughout the width of the myotome. This mediolateral progression of gene expression was coordinated with the lateral migration of slow adaxial cells, which specifically expressed the slow myosin light chain 1 and the SLIM1/FHL1 genes. Subsequently, the fast and slow skeletal muscle isoforms precociously expressed in the course of the mediolateral wave of muscle gene activation became down-regulated in the superficial slow fibers and the deep fast fibers, respectively. Finally, several muscle-specific genes, including troponins, a slow myosin-binding protein C, tropomodulins, and parvalbumin started their transcription only in late embryos. Taken together, these findings show in fish embryos that a common myogenic program is triggered in a mediolateral progression in all muscle cells. The acquisition of the slow phenotype involves the additional activation of several slow-specific genes in migrating adaxial muscle cells. These events are followed by sequential gene activations and repressions in fast and slow muscle cells.

Animals↗

PubMed2006

The Galpha13-Rho signaling axis is required for SDF-1-induced migration through CXCR4.

The CXC chemokine stromal cell-derived factor-1alpha (SDF-1) binds to CXCR4, a seven-transmembrane G protein-coupled receptor that plays a critical role in many physiological processes that involve cell migration and cell fate decisions, ranging from stem cell homing, angiogenesis, and neuronal development to immune cell trafficking. CXCR4 is also implicated in various pathological conditions, including metastatic spread and human immunodeficiency virus infection. Although SDF-1-induced cell migration in CXCR4-expressing cells is sensitive to pertussis toxin treatment, hence involving heterotrimeric G proteins of the G(i) family, whether other G proteins participate in the chemotactic response to SDF-1 is still unknown. In this study, we took advantage of the potent chemotactic activity of SDF-1 in Jurkat T-cells to examine the nature of the heterotrimeric G protein subunits contributing to CXCR4-mediated cell migration. We observed that whereas G(i) and Gbetagamma subunits are involved in SDF-1-induced Rac activation and cell migration, CXCR4 can also stimulate Rho potently leading to the phosphorylation of myosin light chain through the Rho effector, Rho kinase, but independently of G(i). Furthermore, we found that Galpha(13) mediates the activation of Rho by CXCR4 and that the functional activity of both Galpha(13) and Rho is required for directional cell migration in response to SDF-1. Collectively, our data indicate that signaling by CXCR4 to Rho through Galpha(13) contributes to cell migration when stimulated by SDF-1, thus identifying the Galpha(13)-Rho signaling axis as a potential pharmacological target in many human diseases that involve the aberrant function of CXCR4.

Cell Line↗

PubMed1995

Regulation of leukocyte-endothelium interaction and leukocyte transendothelial migration by intercellular adhesion molecule 1-fibrinogen recognition.

Although primarily recognized for its role in hemostasis, fibrinogen is also required for competent inflammatory reactions in vivo. It is now shown that fibrinogen promotes adhesion to and migration across an endothelial monolayer of terminally differentiated myelomonocytic cells. This process does not require chemotactic/haptotactic gradients or cytokine stimulation of the endothelium and is specific for the association of fibrinogen with intercellular adhesion molecule 1 (ICAM-1) on endothelium. Among other adhesive plasma proteins, fibronectin fails to increase the binding of leukocytes to endothelium, or transendothelial migration, whereas vitronectin promotes the binding but not the migration. The fibrinogen-mediated leukocyte adhesion and transendothelial migration could be inhibited by a peptide from the fibrinogen gamma-chain sequence N117NQKIVNL-KEKVAQLEA133, which blocks the binding of fibrinogen to ICAM-1. This interaction could also be inhibited by new anti-ICAM-1 monoclonal antibodies that did not affect the ICAM-1-CD11a/CD18 recognition, thus suggesting that the fibrinogen binding site on ICAM-1 may be structurally distinct from regions previously implicated in leukocyte-endothelium interaction. Therefore, binding of fibrinogen to vascular cell receptors is sufficient to initiate (i) increased leukocyte adhesion to endothelium and (ii) leukocyte transendothelial migration. These two processes are the earliest events of immune inflammatory responses and may also contribute to atherosclerosis.

Amino Acid Sequence↗

PubMed1997

Phenotypic and functional analysis of CD4+ NKRP1A+ human T lymphocytes. Direct evidence that the NKRP1A molecule is involved in transendothelial migration.

In this report, we show that among human CD4+ T lymphocytes 5-20% express the C-type lectin molecule NKRP1A. This lymphocyte subset displays a slightly more limited T cell receptor V beta repertoire than the CD4+ NKRP1A- counterpart. CD4+ NKRP1A+ T lymphocytes are characterized by a high expression of beta 1 and beta 2 integrins, thus representing a T lymphocyte subset that can possibly adhere and migrate through vascular endothelium. Indeed, resting CD4+ NKRP1A+ lymphocytes, differently from the CD4+ NKRP1A- subset, migrated across endothelial cell monolayers in a Transwell chamber system. Pretreatment of CD4+ NKRP1A+ T lymphocytes with an anti-NKRP1A monoclonal antibody (mAb) strongly reduced transendothelial migration, suggesting the involvement of the NKRP1A molecule in the transmigration process. Furthermore, cells of the NKRP1A- Jurkat CD4+ T cell line stably transfected with NKRP1A cDNA migrated more rapidly and efficiently than either untransfected or mock-transfected Jurkat cells. Finally, mAb-mediated cross-linking of NKRP1A molecules in CD4+ T lymphocytes induced the up-regulation of the lymphocyte function-associated antigen 1 Mg(2+)-binding site as well as beta 1 and beta 2 integrin chains. Altogether, these findings suggest that the NKRP1A molecule is involved in transendothelial migration of resting CD4+ T lymphocytes.

Antigens, Surface↗

PubMed2002

Alendronate inhibits lysophosphatidic acid-induced migration of human ovarian cancer cells by attenuating the activation of rho.

Alendronate, a nitrogen-containing bisphosphonate, is a potent inhibitor of bone resorption used for the treatment and prevention of osteoporosis. Recent findings suggest that alendronate and other nitrogen-containing bisphosphonates inhibit the mevalonate pathway and thereby inhibit the synthesis of products derived from this metabolite. This, in turn, prevents the prenylation of a number of small GTPases, which regulate cell growth, motility, and invasion. We studied the effect of alendronate on in vitro migration of human ovarian cancer cells. Lysophosphatidic acid (LPA) induced a dose-dependent increase of migration of cancer cells by promoting Rho/Rho-associated kinase signaling. The induction of cancer cell migration by LPA was inhibited by the addition of alendronate in a dose-dependent manner. Treatment of ovarian cancer cells with alendronate resulted in inactivation of Rho, changes of cell morphology, loss of stress fiber formation, and focal adhesion assembly, and the suppression of phosphorylation of myosin light chain and tyrosine phosphorylation of focal adhesion proteins, which are essential processes for cell migration. The effects of alendronate on cancer cells were prevented by the addition of geranylgeranyol, which is the metabolic intermediate of the mevalonate pathway. These results suggest that alendronate inhibits Rho activation by preventing geranylgeranylation, which results in inhibition of LPA-induced migration of human ovarian cancer cells.

Alendronate↗

PubMed2003

Different migratory and proliferative properties of smooth muscle cells of coronary and femoral artery.

In the human coronary arteries, the intima begins to thicken from early adolescence and shows progressive thickening with age. We compared the response to vascular injury of the coronary and femoral arteries using a canine model. Both incorporation of 5-bromo-2'-deoxyuridine (BrdU) and neointimal formation after balloon injury were significantly greater in the coronary artery than in the femoral artery. Also, the proliferative and migratory activities of coronary smooth muscle cells (SMCs) were significantly greater than those of femoral SMCs in vitro. The level of phosphorylated myosin light chain (phospho-MLC) was higher in coronary SMCs than in femoral SMCs. Y-27632, a specific inhibitor of Rho-kinase, significantly inhibited the PDGF-induced migration of both coronary and femoral SMCs. In contrast, the migration of coronary SMCs, but not femoral SMCs, was inhibited by ML-9, a specific inhibitor of myosin light chain kinase (MLCK). These findings suggest that the contribution of Rho-kinase and MLCK differs between the different arteries. They also suggest that a neointima develops more easily in the coronary artery than in the femoral artery because of the greater proliferative and migratory activity of coronary SMCs. Differential activation of MLC might partly explain the increased proliferation and migration of coronary SMCs.

Amides↗

PubMed2006

Ibuprofen inhibition of tendon cell migration and down-regulation of paxillin expression.

Sports-related tendon injuries are commonly treated with nonsteroidal antiinflammatory drugs. Tendon healing requires migration of tendon cells to the repair site, followed by proliferation and synthesis of the extracellular matrix. This study was designed to determine the effect of ibuprofen on the migration of tendon cells intrinsic to rat Achilles tendon. Whether a correlation exits between this effect and the expression of paxillin, which is a positive regulator of cell spreading and migration, was also investigated. The migration of tendon cells was evaluated ex vivo by counting the number of initial outgrowths from the tendon explants and in vitro by transwell filter migration assay. The spreading of tendon cells in culture was also evaluated microscopically. The mRNA and protein expressions of paxillin were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Dose-dependent ibuprofen inhibition was demonstrated on the migration of tendon cells both ex vivo, and in vitro. Similar inhibition was also observed on the spreading of tendon cells. Suppression of mRNA expression and protein level of paxillin was revealed by RT-PCR and Western blot analyses. The expression of focal adhesion kinase (FAK) and tyrosine phosphorylation of FAK remained unchanged. In conclusion, ibuprofen inhibits tendon cell migration in a process that is probably mediated by the down-regulation of paxillin.

Achilles Tendon↗

PubMed1999

Fibrin gel induces the migration of smooth muscle cells from rabbit aortic explants.

A major step in the pathogenesis of atherosclerosis is the vectorial migration of smooth muscle cells (SMCs) from the arterial media into the intima. Although subcultured SMCs usually show synthetic phenotype, the behaviour of contractile SMCs may be crucial for the subsequent migration of the cells. In the present study, we utilized an in vitro assay system to evaluate the effects of fibrin gels on the migration of SMCs from explants taken from rabbit aorta. After cultured for 5-7 days in a serum-free condition, SMCs appeared from explants covered with fibrin gel. The cells were positive on immunostaining for SMC specific alpha-actin. No migration of SMCs from the control explants without fibrin gel was observed. Then the percentage of explants showing cell migration and the number of migrating cells increased with time. The migration of SMCs into fibrin gels was not dependent on the concentration of fibrinogen used for the preparation of fibrin gel in the range of 1.5-3 mg/ml. Variations of thrombin concentration in the range of 0.25-1.25 U/ml had no significant effect. However, there was less migration of SMCs with higher concentrations of thrombin. Thrombin inhibitors, hirudin and PPACK had no significant effect on the migration of SMCs. An RGD-containing peptide, GRGDS inhibited the migration of SMCs although a control peptide GRGES at the same concentration had no significant effect. A monoclonal antibody to alphavbeta3, LM609, completely inhibited the migration of SMCs from the explants, suggesting that alphavbeta3 integrin is involved in the migration of SMCs into fibrin gels. SMCs which migrated from the explants showed the positive staining with the monoclonal antibodies against SMC myosin heavy chain isoforms, SMemb, SM1 and SM2, suggesting that they are in an intermediate state changing from contractile to synthetic state. In conclusion, the present study showed that fibrin gel induces the migration of SMCs from explants into itself and the process may not need other growth factors or cytokines.

Animals↗

PubMed1994

Reciprocal expression of laminin A-chain isoforms along the crypt-villus axis in the human small intestine.

BACKGROUND/AIMS: Intestinal epithelial cell proliferation, migration, and differentiation are susceptible to various influences along the crypt-villus axis including compositional changes in the basement membrane and differential expression of receptors for these components. However, laminin has been consistently detected at the epithelial basement membrane without significant variation in relation to the crypt-villus functional unit. The aim of this study was to examine the distribution of individual laminin chains. METHODS: The patterns of distribution of laminin A, M (an A-chain variant), B1, and B2 chains as well as the integrins alpha 6 beta 1 and alpha 6 beta 4, two laminin receptors, were determined by indirect immunofluorescence in the adult human small intestine. RESULTS: Markedly distinct patterns of laminin chain expression were observed along the crypt-villus axis. The A chain was found predominantly associated with the differentiated epithelial cells on the villus whereas the M chain was restricted to the basement membrane of crypts. However, both B1 and B2 chains were detected all along the intestinal basement membrane. Furthermore, alpha 6 beta 1 and alpha 6 beta 4 integrins were found to be expressed by all enterocytes. CONCLUSIONS: These observations show a reciprocal expression of laminin isoforms along the crypt-villus axis and support the concept that the intestinal epithelial basement membrane is subjected to intricate compositional changes.

Adult↗

PubMed1996

Anchoring complex components laminin-5 and type VII collagen in intestine: association with migrating and differentiating enterocytes.

Anchoring complex component laminin-5 and its subunits laminin (Ln)-alpha3 and Ln-beta3 chains, Type VII collagen, and integrin chains alpha3, alpha6, and beta4 were studied in developing and adult human intestine and compared with findings on Ln-alpha1 and Ln-alpha2 chains. In adult human duodenum, jejunum, and ileum, Ln-5 detected with a polyclonal antiserum and Ln-alpha3 and Ln-beta3 chains, detected with monoclonal antibodies (MAbs), were restricted to the epithelial basement membranes (BMs) of villi, whereas Ln-alpha2 chain was seen only focally in crypt bottoms. In double labeling experiments, the stretch of crypt BM corresponding to the proliferative cell compartment was found to be devoid of both Ln-alpha3 and Ln-alpha2 chains. Double labeling for Ln-5 and proliferating cell nuclear antigen also showed an abrupt onset of Ln-5 expression exactly at the upper edge of the proliferative cell compartment. Type VII collagen was negligible in duodenum and showed a rising duodenal-ileal gradient localizing to villar BMs. Double labeling for Ln-5 and Type VII collagen, however, indicated only partial co-distribution in the intestine. Electron microscopy of ileum revealed both anchoring filaments and anchoring fibrils but no hemidesmosomal plaques. Our results demonstrate the expression of Ln-5 in BMs outside of stratified epithelia and indicate that Ln-5 in the intestine is associated with the compartment of migrating and differentiating enterocytes. Absence of hemidesmosomes and the presence of other anchoring complex components, such as Ln-5, Type VII collagen, and integrin chains alpha3, alpha6, and beta4, suggests unique properties for epithelial cell attachment in the intestine.

Adult↗

PubMed2001

[Breast cancer with metastatic invasion of the sentinel lymph node in an internal mammary chain and with axillary chains free of tumor lesionS].

The lymphoscintigraphy is a widely accepted procedure to detect the sentinel node in breast cancer. This is a case report of a 45 year old woman diagnosed of breast cancer who was referred to the nuclear medicine facility to perform the sentinel node detection procedure. The lymphoscintigraphy prior to surgery shows a double pathway in the tracer migration: one going to the axillary area and the second to the internal mammary chain and shows hot spots that represent the sentinel nodes. After surgical removal of those nodes, the pathological analysis report indicated tumor infiltration in the internal mammary chain sentinel node with all axillary nodes free of malignant cells. The aim of this report is to emphasize the importance of performing a pathological analysis of all the sentinel nodes detected in lymphoscintigraphy.

Axilla↗

PubMed1996

The ferritins: molecular properties, iron storage function and cellular regulation.

The iron storage protein, ferritin, plays a key role in iron metabolism. Its ability to sequester the element gives ferritin the dual functions of iron detoxification and iron reserve. The importance of these functions is emphasised by ferritin's ubiquitous distribution among living species. Ferritin's three-dimensional structure is highly conserved. All ferritins have 24 protein subunits arranged in 432 symmetry to give a hollow shell with an 80 A diameter cavity capable of storing up to 4500 Fe(III) atoms as an inorganic complex. Subunits are folded as 4-helix bundles each having a fifth short helix at roughly 60 degrees to the bundle axis. Structural features of ferritins from humans, horse, bullfrog and bacteria are described: all have essentially the same architecture in spite of large variations in primary structure (amino acid sequence identities can be as low as 14%) and the presence in some bacterial ferritins of haem groups. Ferritin molecules isolated from vertebrates are composed of two types of subunit (H and L), whereas those from plants and bacteria contain only H-type chains, where 'H-type' is associated with the presence of centres catalysing the oxidation of two Fe(II) atoms. The similarity between the dinuclear iron centres of ferritin H-chains and those of ribonucleotide reductase and other proteins suggests a possible wider evolutionary linkage. A great deal of research effort is now concentrated on two aspects of ferritin: its functional mechanisms and its regulation. These form the major part of the review. Steps in iron storage within ferritin molecules consist of Fe(II) oxidation, Fe(III) migration and the nucleation and growth of the iron core mineral. H-chains are important for Fe(II) oxidation and L-chains assist in core formation. Iron mobilisation, relevant to ferritin's role as iron reserve, is also discussed. Translational regulation of mammalian ferritin synthesis in response to iron and the apparent links between iron and citrate metabolism through a single molecule with dual function are described. The molecule, when binding a [4Fe-4S] cluster, is a functioning (cytoplasmic) aconitase. When cellular iron is low, loss of the [4Fe-4S] cluster allows the molecule to bind to the 5'-untranslated region (5'-UTR) of the ferritin m-RNA and thus to repress translation. In this form it is known as the iron regulatory protein (IRP) and the stem-loop RNA structure to which it binds is the iron regulatory element (IRE). IREs are found in the 3'-UTR of the transferrin receptor and in the 5'-UTR of erythroid aminolaevulinic acid synthase, enabling tight co-ordination between cellular iron uptake and the synthesis of ferritin and haem. Degradation of ferritin could potentially lead to an increase in toxicity due to uncontrolled release of iron. Degradation within membrane-encapsulated "secondary lysosomes' may avoid this problem and this seems to be the origin of another form of storage iron known as haemosiderin. However, in certain pathological states, massive deposits of "haemosiderin' are found which do not arise directly from ferritin breakdown. Understanding the numerous inter-relationships between the various intracellular iron complexes presents a major challenge.

Animals↗

PubMed2004

Using temporally spaced sequences to simultaneously estimate migration rates, mutation rate and population sizes in measurably evolving populations.

We present a Bayesian statistical inference approach for simultaneously estimating mutation rate, population sizes, and migration rates in an island-structured population, using temporal and spatial sequence data. Markov chain Monte Carlo is used to collect samples from the posterior probability distribution. We demonstrate that this chain implementation successfully reaches equilibrium and recovers truth for simulated data. A real HIV DNA sequence data set with two demes, semen and blood, is used as an example to demonstrate the method by fitting asymmetric migration rates and different population sizes. This data set exhibits a bimodal joint posterior distribution, with modes favoring different preferred migration directions. This full data set was subsequently split temporally for further analysis. Qualitative behavior of one subset was similar to the bimodal distribution observed with the full data set. The temporally split data showed significant differences in the posterior distributions and estimates of parameter values over time.

Biological Evolution↗

PubMed1989

Biosynthesis of the protein encoded by the c-met proto-oncogene.

The proto-oncogene c-met encodes a transmembrane protein with structural features of a growth factor receptor. We have previously shown that the c-met protein (c-Met) is a heterodimer of two disulphide linked chains of 50 kd (alpha) and 145 kd (beta). In this work we have studied the biosynthesis of the c-met product in a gastric carcinoma cell line (GTL-16) where the c-met gene is amplified and overexpressed. Following metabolic labelling of the cells in the presence of tunicamycin, anti-met antibodies immunoprecipitate a protein of 150 kd. In pulse-chase experiments carried out in the absence of tunicamycin, a 170 kd product appears first. Within the next few minutes, this precursor modifies its SDS migration, probably as a consequence of modification(s) of its intra-chain disulphide bonds. After 45 min of chase, this single polypeptide precursor is cleaved to form a 50 kd alpha subunit and a 145 kd beta subunit that are joined by disulphide bonds in an alpha beta complex with an apparent molecular weight of 190 kd. The presence of N-linked oligosaccharides in both the precursor and the mature protein was shown by enzymatic de-glycosylation of the immunoprecipitated proteins. The half-life of the mature protein was calculated to be approximately 5h. The c-met protein has similar structure and biosynthesis in other human cell lines.

Cell Line↗

PubMed1996

Identification of macrophage migration inhibitory factor in human leukemia HL-60 cells and its induction by lipopolysaccharide.

Cytokines play an important role in inflammation and immunity. In this study, we examined the expression and presence of human macrophage migration inhibitory factor (MIF) in human myelomonocytic leukemia cell line, HL-60 by reverse transcription-polymerase chain reaction (RT-PCR) and immunological methods (Western blot analysis and immunohistochemistry), respectively. The RT-PCR showed that MIF mRNA was constitutively expressed, and the expression was further induced by lipopolysaccharide (LPS) stimulation. The expression was upregulated by LPS at the range of 10 pg/ml to 10 ng/ml; however, it decreased at doses higher than 100 ng/ml. The expression reached the maximum 12 hr after the stimulation, but substantially decreased by 24 hr. Western blot analysis and immunohistochemistry using an anti-human MIF antibody revealed the presence of MIF protein in cytoplasm of the cells. The pathophysiological role of MIF in HL-60 cells has not been fully understood; however, the regulation of MIF mRNA expression by LPS suggests the possibility that the cytokine plays an important role in inflammatory events of leukemia.

Blotting, Western↗

PubMed1992

A dominant mutation in the COL1A1 gene that substitutes glycine for valine causes recurrent lethal osteogenesis imperfecta.

Type I collagen chains of a proband from a family with recurrent lethal osteogenesis imperfecta (OI) migrated as a doublet when submitted to gel electrophoresis. Cyanogen bromide (CNBr) peptide mapping demonstrated that the post-translational over-modifications were initiated in alpha 1ICB7. Chemical cleavage of cDNA-RNA heteroduplexes identified a mismatch in the alpha 1I cDNA; this mismatch was subsequently confirmed by sequencing a 249-bp fragment amplified by the polymerase chain reaction. A G to T transition in the second base of the first codon of exon 41 resulted in the substitution of glycine 802 by valine. This mutation impaired collagen secretion by dermal fibroblasts. The over-modified chains were retained intracellularly and melted at a lower temperature than normal chains. Collagen molecules synthesized by parental fibroblasts had a normal electrophoretic mobility, but hybridization of genomic DNA with allele-specific oligonucleotides revealed the presence of the mutant allele in the mother's leukocytes. The mutation was not detected in her fibroblasts consistent with the protein data. These results support the hypothesis that somatic and germ-line mosaicism in the phenotypically normal mother explain the recurrence of OI.

Alleles↗

PubMed1982

Type IIB to IIA fiber transformation in intermittently stimulated rabbit muscles.

Long-term intermittent stimulation (10 Hz, 8 h/day, 7 wk) of the fast-twitch tibialis anterior results in a complete transformation of type IIB fibers to type IIA fibers. This is shown by the histochemical ATPase reaction and by a decrease in Ca2+-uptake ability by the sarcoplasmic reticulum. Furthermore, as shown by studies on bulk myosin and on single fibers, the LC1-to-LC3 light chain ratio is increased on sodium dodecylsulfate gel electrophoretograms, and there are changes in the myosin isozyme pattern manifested on pyrophosphate gels under nondissociating conditions. Thus the staining intensity of the slower moving putative LC1 homodimer band increases, and there is a difference in migration velocity between stimulated and unstimulated isozymes suggesting a possible difference in the heavy chain. This study underlines the importance of the stimulation schedule in determining whether a fast-to-slow transformation or a shift in subtype takes place.

Adenosine Triphosphatases↗