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PubMed1991

Recombinant antibodies.

Many fundamental advances in our understanding of the structure and function of eukaryotic genes were derived from the study of antibody genes. Examples include mRNA splicing and rearrangement to generate antibody diversity. The capacity to immortalize an individual B cell using cell fusion permitted the generation of monoclonal antibodies. Monoclonal antibodies have had wide application in many fields of the life sciences and beyond. Recent advances permitting manipulation of antibody genes using recombinant DNA techniques offer many advantages over conventional somatic cell hybridization techniques. Rodent monoclonals can be "humanized" and antibody isotype readily changed. Grafting of the complementarity determining regions from rodent to human framework regions demonstrated the importance of these hypervariable portions of the immunoglobulin to the integrity of the antibody combining site. Recombinant monoclonal antibodies (rMAb) or fragments thereof have been successfully produced in both prokaryotic and eukaryotic hosts at levels equal to those produced by hybridomas. Successful efforts to express rMAbs in plants and other large capacity systems suggest that rMAbs can be produced inexpensively. Use of antibody catalysis and antibodies mimicking various receptors or ligands have numerous applications. Technology developed to immortalize the heavy and light chain repertoire permits the generation in vitro of recombinatorial libraries of antibodies. The capacity to artificially generate high-affinity antibodies in vitro using the methods of recombinant DNA technology has enormous pharmaceutical and industrial potential.

Animals↗

PubMed2003

Of splice and men: what does the distribution of IKAP mRNA in the rat tell us about the pathogenesis of familial dysautonomia?

Familial dysautonomia (FD) is the best-known and most common member of a group of congenital sensory/autonomic neuropathies characterized by widespread sensory and variable autonomic dysfunction. As opposed to the sensory/motor neuropathies, little is known about the causes of neuronal dysfunction and loss in the sensory/autonomic neuropathies. FD involves progressive neuronal degeneration, has a broad impact on the operation of many of the body's systems, and leads to a markedly reduced quality of life and premature death. In 2001, we identified two mutations in the IKBKAP gene that result in FD. IKBKAP encodes IKAP, a member of the putative human holo-Elongator complex, which may facilitate transcription by RNA polymerase II. Whether or not the Elongator plays this role is moot. The FD mutation found on >99.5% of FD chromosomes does not cause complete loss of function. Instead, it results in a tissue-specific decrease in splicing efficiency of the IKBKAP transcript; cells from patients retain some capacity to produce normal mRNA and protein. To better understand the relationship between the genotype of FD patients and their phenotype, we have used in situ hybridization histochemistry to map the IKAP mRNA in sections of whole rat embryos. The mRNA is widely distributed. Highest levels are in the nervous system, but substantial amounts are also present in peripheral organs.

Animals↗

PubMed2001

C1-inhibitor deficiency and angioedema.

C1-inhibitor deficiency can be inherited or acquired; both conditions lead to recurrent angioedema that can be life threatening when the larynx is involved (hereditary angioedema, HAE; acquired angioedema, AAE). The genetic defect is due to the heterozygous deficiency of C1-Inh that is transmitted as an autosomal dominant trait. Mutations causing HAE have been found distributed over all exons and splice sites of C1-Inh structural gene: only a few of them have been found more than once. Depending on DNA defect, C1-Inh is not transcribed, or not translated or not secreted. Finally, in 15% of HAE patients, an antigenically normal, but non-functional C1-Inh is present in serum (HAE type II). C1-Inh deficiency can be acquired, due to an accelerated consumption. Such an accelerated consumption can depend on circulating autoantibodies that bind C1-Inh causing its inactivation and catabolism; or to associated diseases, usually lymphoproliferative diseases, that consume C1-Inh with different mechanisms. Effective therapies can prevent or revert angioedema symptoms in C1-Inh deficiency, the main problem of this condition remaining misdiagnosis. The common knowledge that angioedema is an allergic symptom frequently prevents a correct diagnostic approach: C1-Inh deficiency goes unrecognized and the disease can still be lethal. Correct prophylactic treatment is based on attenuated androgens in HAE and on antifibrinolytic agents in AAE. Life threatening laryngeal attacks and severe abdominal attacks are effectively reverted, in both conditions, with C1-Inh plasma concentrate. A special remark to this treatment should be made for autoantibody-mediated AAE where very high doses can be needed depending on the rate of C1-Inh consumption.

Angioedema↗

PubMed1998

The Ig heavy chain 3' end confers a posttranscriptional processing advantage to Bcl-2-IgH fusion RNA in t(14;18) lymphoma.

The chromosomal translocation t(14;18) in lymphoma leads to an overproduction of the Bcl-2 protein on the basis of increased Bcl-2 mRNA levels. Whereas the juxtaposition of Bcl-2 with the Ig heavy chain locus causes a transcriptional activation, 70% of the lymphomas also produce Bcl-2-Ig fusion RNAs with Ig 3' ends. Using S1 nuclease protection assays that can discriminate between nuclear RNA precursors and spliced mRNA, we found that the fusion RNAs in t(14;18) cell lines exhibit an additional posttranscriptional processing advantage. Transfection experiments with artificial genes containing various Bcl-2 or Ig 3' ends show that this effect is (1) related to RNA splicing and/or nucleocytoplasmic transport; (2) independent of transcriptional activation by the heavy chain enhancer; (3) dependent on the presence of the JH-CH and C-gamma1 Ig introns; and (4) tissue specific for B cells. This constitutes a novel mechanism of oncogene deregulation unrelated to transcriptional activation or half-life prolongation. The data further support the existence of a tissue-specific posttranscriptional pathway of Ig regulation in B cells.

Actins↗

PubMed2002

The protein kinase C beta II exon confers mRNA instability in the presence of high glucose concentrations.

Previous studies showed that short term exposure of cells to high glucose destabilized protein kinase C (PKC) betaII mRNA, whereas PKCbetaI mRNA levels remained unaltered. Because PKCbeta mRNAs share common sequences other than the PKCbetaII exon encoding a different carboxyl terminus, we examined PKCbetaII mRNA for a cis-acting region that could confer glucose-induced destabilization. A beta-globin/growth hormone reporter con struct containing the PKCbetaII exon was transfected into human aorta and rat vascular smooth muscle cells (A10) to follow glucose-induced destabilization. Glucose (25 mm) exposure destabilized PKCbetaII chimeric mRNA but not control mRNA. Deletion analysis and electrophoretic mobility shift assays followed by UV cross-linking experiments demonstrated that a region introduced by inclusion of the betaII exon was required to confer destabilization. Although a cis-acting element mapped to 38 nucleotides within the betaII exon was necessary to bestow destabilization, it was not sufficient by itself to confer complete mRNA destabilization. Yet, in intact cells antisense oligonucleotides complementary to this region blocked glucose-induced destabilization. These results suggest that this region must function in context with other sequence elements created by exon inclusion involved in affecting mRNA stability. In summary, inclusion of an exon that encodes PKCbetaII mRNA introduces a cis-acting region that confers destabilization to the mRNA in response to glucose.

Animals↗

PubMed1991

High fidelity developmental excision of Tec1 transposons and internal eliminated sequences in Euplotes crassus.

Following the sexual phase of its life cycle, the hypotrichous ciliate Euplotes crassus transforms a copy of its chromosomal micronucleus into a transcriptionally active macronucleus containing short, linear, gene-sized DNA molecules. Tens of thousands of DNA breakage and joining, or splicing, events occur during macronuclear development. The DNA removed by such events includes transposon-like elements, referred to as Tec1 elements, as well as segments of unique sequence DNA, termed internal eliminated sequences (IESs). Both types of elements are bounded by short direct repeats. In the current study, a polymerase chain reaction (PCR) and DNA sequencing strategy has been used to examine the fidelity of excision of two Tec1 elements and three IESs. In all cases, the vast majority of excision events were found to be precise, with one copy of the terminal direct repeats retained at the empty site in the macronuclear DNA molecule. These results, in combination with previous studies that have characterized the excised DNA elements, indicate that the two products of excision (the free element and the macronuclear DNA molecule) share DNA sequences. This suggests that excision events are initiated by staggered cuts in the chromosomal DNA.

Animals↗

PubMed2003

Mice with a deletion in the first intron of the Col1a1 gene develop age-dependent aortic dissection and rupture.

The functional significance of the first intron of the Col1a1 gene in regulation of type I collagen synthesis remains uncertain. A previous study in mice established that a mutated Col1a1 allele that lacked a large fraction of the first intron, but retained the sequences required for normal splicing, was subject to an age- and tissue-dependent decrease in expression. In this study, we report that mice homozygous for this deletion are predisposed to dissection and rupture of the aorta during their adult life. Aortic dissection was not detected in autopsies of heterozygous animals or their littermate controls. Electron micrographs revealed fewer collagen fibrils and less compacted, irregular elastic lamellae in the aortic walls of homozygous mutant animals. Northern analysis of aortic RNA from 2.5- and 12-month-old homozygous mutant mice revealed that Col1a1 mRNA levels were decreased by 29% and 42%, respectively, relative to those of control littermates. In 12-month-old heterozygotes, the decrease was 32%. Allele-specific amplification of heterozygous cDNAs demonstrated that this reduction was limited to transcripts from the mutant allele. The collagen content of the aortas of homozygous mutant mice was also significantly lower in comparison to that of age-matched, control animals. These data establish that the integrity of the aortic wall depends on an adequate content of type I collagen, and that continued synthesis of collagen in the aorta as a function of age is critically dependent on sequences in the first intron of the Col1a1 gene.

Age Factors↗

PubMed2006

Binding of the polypyrimidine tract-binding protein-associated splicing factor (PSF) to the hepatitis delta virus RNA.

The hepatitis delta virus (HDV) has a very limited protein coding capacity and must rely on host proteins for its replication. A ribonucleoprotein complex was detected following UV cross-linking between HeLa nuclear proteins and an RNA corresponding to the right terminal stem-loop domain of HDV genomic RNA. Mass spectrometric analysis of the complex revealed the polypyrimidine tract-binding protein-associated splicing factor (PSF) as a novel HDV RNA-interacting protein. Co-immunoprecipitation demonstrated the interaction between HDV RNA and PSF both in vitro in HeLa nuclear extract and in vivo within HeLa cells containing both polarities of the HDV genome. Analysis of the binding of various HDV-derived RNAs to purified, recombinant PSF further confirmed the specificity of the interaction and revealed that PSF directly binds to the terminal stem-loop domains of both polarities of HDV RNA. Our findings provide evidence of the involvement of a host mRNA processing protein in the HDV life cycle.

Amino Acid Sequence↗

PubMed2002

The osteopetrotic mutation toothless (tl) is a loss-of-function frameshift mutation in the rat Csf1 gene: Evidence of a crucial role for CSF-1 in osteoclastogenesis and endochondral ossification.

The toothless (tl) mutation in the rat is a naturally occurring, autosomal recessive mutation resulting in a profound deficiency of bone-resorbing osteoclasts and peritoneal macrophages. The failure to resorb bone produces severe, unrelenting osteopetrosis, with a highly sclerotic skeleton, lack of marrow spaces, failure of tooth eruption, and other pathologies. Injections of CSF-1 improve some, but not all, of these. In this report we have used polymorphism mapping, sequencing, and expression studies to identify the genetic lesion in the tl rat. We found a 10-base insertion near the beginning of the open reading of the Csf1 gene that yields a truncated, nonfunctional protein and an early stop codon, thus rendering the tl rat CSF-1(null). All mutants were homozygous for the mutation and all carriers were heterozygous. No CSF-1 transcripts were identified in rat mRNA that would avoid the mutation via alternative splicing. The biology and actions of CSF-1 have been elucidated by many studies that use another naturally occurring mutation, the op mouse, in which a single base insertion also disrupts the reading frame. The op mouse has milder osteoclastopenia and osteopetrosis than the tl rat and recovers spontaneously over the first few months of life. Thus, the tl rat provides a second model in which the functions of CSF-1 can be studied. Understanding the similarities and differences in the phenotypes of these two models will be important to advancing our knowledge of the many actions of CSF-1.

Alternative Splicing↗

PubMed2006

Early rapid rise in EAAT2 expression follows the period of maximal seizure susceptibility in human brain.

Seizures are relatively common in the first weeks of life and can have lasting effects on brain development due to glutamate excitotoxicity. The excitatory amino acid transporter 2 (EAAT2) is responsible for the majority of glutamate uptake in the brain and mice with this gene deleted die from seizures. Therefore, we reasoned that developmental changes in the expression of EAAT2 might correlate with the period of increased susceptibility to seizures in humans, reflecting a changing vulnerability to excitotoxic insults. Expression levels of eight splice forms of EAAT2 were measured using quantitative RT-PCR from human prefrontal cortex and hippocampus at 1-2 months, 1-2 years, 8 years, 15-16 years, and 18-22 years of age. There was a significant increase in expression of most isoforms between 1-2 months and 1-2 years with isoform-specific patterns after that period. The increase in EAAT2 expression during the first 2 years of life corresponds to a period of maximal synapse formation and other changes in the glutamatergic system such as increased NMDA receptor expression. Moreover, the low expression of EAAT2 in the first months of life corresponds to the period of maximum susceptibility to seizures.

Adolescent↗

PubMed2006

Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome.

Defects in the xeroderma pigmentosum type B (XPB) gene (ERCC3), a DNA helicase involved in nucleotide excision repair (NER) and an essential subunit of the basal transcription factor, TFIIH, have been described in only three families. We report three new XPB families: one has two sisters with relatively mild xeroderma pigmentosum (XP) symptoms not previously associated with XPB mutations and two have severe XP/Cockayne syndrome (CS) complex symptoms. All XP-B cells had reduced NER and post-ultraviolet (UV) cell viability. Surprisingly, cells from the milder XP sisters had the same missense mutation (c.296T>C, p.F99S) that was previously reported in two mild XP/CS complex brothers. These cells had higher levels of XPB protein than the severely affected XP/CS complex patients. An XPB expression vector with the p.F99S mutation partially complemented the NER defect in XP-B cells. The three severely affected XP/CS complex families all have the same splice acceptor site mutation (c.2218-6C>A, p.Q739insX42) in one allele. This resulted in alteration of 41 amino acids at the C terminus, producing partial NER complementation. This limited number of mutations probably reflects the very restricted range of alterations of this vital protein that are compatible with life. We found new mutations in the second allele yielding markedly truncated proteins in all five XP or XP/CS complex families: c.1273C>T, p.R425X; c.471+1G>A, p.K157insTSDSX; c.807-808delTT, p.F270X; c.1421-1422insA, p.D474EfsX475; and c.1633C>T, p.Q545X. The remarkable phenotypic heterogeneity of XPB is associated with partially active missense mutations in milder patients while severe XP/CS complex patients have nonsense mutations in both alleles with low levels of altered XPB proteins.

Abnormalities, Multiple↗

PubMed1999

Identification of the mammalian homolog of the splicing regulator Suppressor-of-white-apricot as a thyroid hormone regulated gene.

Mammalian brain development is controlled by thyroid hormone through the regulation of target genes. In this study, we describe for the first time that a splicing regulator gene is under thyroid hormone control in the rat brain during the critical period of neuronal differentiation. By differential display, we have identified the mammalian homolog of the Drosophila splicing regulator Suppressor-of-white-apricot (SWAP) as a thyroid hormone-regulated gene in an immortal line of rat neuroblasts, E18 cells. Using Northern blotting and in situ hybridization, we found that expression of SWAP is under thyroid control in the developing rat brain. SWAP gene expression is highest during the first 10 days of life (P0-P10), preferentially in cerebral cortex, cerebellum, subventricular epithelium, piriform cortex, hippocampus, amygdala, and caudate putamen. At later stages (P15-P30) SWAP expression decreases, being detectable only in the cerebellum, hippocampus, and layers II/III of cerebral and piriform cortexes. We found that hypothyroidism causes an abnormal high level of SWAP RNA expression at P5-P15 throughout the brain except the cerebellum. Significantly, thyroid hormone treatment in vivo of hypothyroid animals led to a normalization of SWAP RNA expression. Furthermore, similar hormone treatment caused a decrease in SWAP expression in control rats. By modulating the expression of SWAP and perhaps other splicing regulators thyroid hormone may exert wide regulatory effects on multiple genes. The regulation of SWAP gene defines a novel mechanism of action of thyroid hormone which can be important for its effects in the developing brain.

Amino Acid Sequence↗

PubMed2003

High-throughput genotyping by DHPLC of the dihydropyrimidine dehydrogenase gene implicated in (fluoro)pyrimidine catabolism.

Dihydropyrimidine dehydrogenase (DPD) is the first and rate-limiting enzyme in the degradation of pyrimidines and pyrimidine base analogs including the anticancer drugs 5-fluorouracil (5-FU) and Xeloda. A decreased DPD enzyme activity has been described in cancer patients experiencing severe and life-threatening toxicity after 5-FU treatment and distinct sequence variants in the DPD gene (DPYD) have been associated with impaired enzyme function. The most prominent mutation in the DPD deficient patient group, a mutation in the splicing donor consensus sequence of intron 14, IVS14+1g>a, resulting in a truncated protein, has been observed in the Caucasian population at frequencies as high as 0.91%-0.94%. This underlines the need for a test system for DPYD mutations in patients undergoing chemotherapy with 5-FU or with Xeloda. To set up a fast and sensitive method to identify variant DPYD alleles, we analyzed 50 healthy individuals by denaturing high performance liquid chromatography (DHPLC). A primer set spanning the whole coding region and the exon-intron boundaries of DPYD was used. In addition, a cDNA-based assay was developed to rapidly identify the 165 base pair deletion in the corresponding RNA of IVS14+1g>a mutation carriers. The optimal mutation detection was elaborated for each of the PCR fragments. DHPLC analysis detected 5 different genetic alterations occurring in the coding region of the gene, as well as 10 intronic sequence variants, respectively. In conclusion, high-throughput screening for DPYD variants by DHPLC may be a reliable tool in the investigation of the molecular basis of DPD deficiency. Furthermore, it will help to identify patients at risk for toxic side effects upon chemotherapy using 5-FU and will facilitate individual treatment of patients.

Adult↗

PubMed2003

In silico study of breast cancer associated gene 3 using LION Target Engine and other tools.

Sequence analysis of individual targets is an important step in annotation and validation. As a test case, we investigated human breast cancer associated gene 3 (BCA3) with LION Target Engine and with other bioinformatics tools. LION Target Engine confirmed that the BCA3 gene is located on 11p15.4 and that the two most likely splice variants (lacking exon 3 and exons 3 and 5, respectively) exist. Based on our manual curation of sequence data, it is proposed that an additional variant (missing only exon 5) published in a public sequence repository, is a prediction artifact. A significant number of new orthologs were also identified, and these were the basis for a high-quality protein secondary structure prediction. Moreover, our research confirmed several distinct functional domains as described in earlier reports. Sequence conservation from multiple sequence alignments, splice variant identification, secondary structure predictions, and predicted phosphorylation sites suggest that the removal of interaction sites through alternative splicing might play a modulatory role in BCA3. This in silico approach shows the depth and relevance of an analysis that can be accomplished by including a variety of publicly available tools with an integrated and customizable life science informatics platform.

Adaptor Proteins, Signal Transducing↗

PubMed1993

RNA as a catalyst: natural and designed ribozymes.

RNA can catalyse chemical reactions through its ability to fold into complex three-dimensional structures and to specifically bind small molecules and divalent metal ions. The 2'-hydroxyl groups of the ribose moieties contribute to this exceptional reactivity of RNA, compared to DNA. RNA is not only able to catalyse phosphate ester transfer reactions in ribonucleic acids, but can also show amino-acyl esterase activity, and is probably able to promote peptide bond formation. Bearing its potential for functioning both as a genome and as a gene product, RNA is suitable for in vitro evolution experiments enabling the selection of molecules with new properties. The growing repertoire of RNA catalysed reactions will establish RNA as a primordial molecule in the evolution of life.

Base Sequence↗

PubMed1985

The notion of primordial building blocks in construction of genes and transcriptional and processing errors due to random occurrence of oligonucleotide signal sequences.

Contrary to the currently popular belief, genes (flanking and internal noncoding sequences included) that specify beta-sheet and alpha-helical proteins are not unique sequences, rather they are degenerate repeats of short primordial building block sequences that are 45 to 48 bases long in the case of genes belonging to the beta-2-microglobulin superfamily. Accordingly, a large number of base decamers, nonomers, octamers, heptamers and hexamers recur within every gene. One consequence of the above is the random and inadvertent occurrence within genes of various oligonucleotide signal sequences for initiation and termination of transcription as well as for processing of transcripts by removal of intervening sequences. Inadvertent transcription of nonsense sequences and missplicing of transcripts may increase with age and contribute to the aging process. There is little doubt that the life span, being one of the species' characteristics, is genetically programmed. The question remains, however, as to whether or not such a program is embodied in each and every somatic cell type. If the cessation of cell proliferation is regarded synonymous with senescence, one is placed in the awkward position of having to state that most neurons of the central nervous system enter the state of senescence at the neonatal stage. An alternative to the above is the assumption of central control; e.g., the programmed secretion of an aging peptide hormone by the pituitary. To be sure somatic cells accumulate randomly sustained mutations as do germ cells and whatever other genetic mishaps (e.g., deletions, duplications) that may affect somatic cells also occur in germ cells. Yet, the monophyletic germ line on this earth has persisted for three billion years and has the potential of being immortal. Furthermore there can be no direct cause-and-effect relationship between the process of differentiation and the loss of immortality, for spermatozoa are one of the most, if not the most, differentiated cell types that can be found in the body. Nevertheless, if one's scope is confined to the types of genetic mishaps that may afflict somatic cells in their given life span, the one particular type that has hitherto escaped notice should be considered.

Aging↗

PubMed2004

Near-miss apparent SIDS from adrenal crisis.

OBJECTIVE: Adrenal crisis from salt-losing congenital adrenal hyperplasia (CAH) typically occurs in the first 2 weeks of life. We evaluated 3 infants with adrenal crisis who presented at 6 to 8 months of age with near-miss sudden infant death syndrome (SIDS). SUBJECTS: Three 46,XY phenotypic female infants presented near death at 6 to 8 months of age with adrenal crisis and unmeasurable steroid hormones consistent with congenital lipoid adrenal hyperplasia (lipoid CAH). METHODS: We sequenced genes potentially causing this phenotype: steroidogenic acute regulatory protein (StAR), the cholesterol side-chain cleavage enzyme, adrenodoxin reductase, adrenodoxin, and steroidogenic factor 1 (SF1). Site-directed mutagenesis and functional assays were performed for the missense mutation. RESULTS: Hormonal values showed complete absence of adrenal and gonadal steroids. Patient 1 was a compound heterozygote for missense mutation R140P and an mRNA splice donor site mutation in the StAR gene. The R140P mutation was wholly inactive in vitro. Patient 2 was homozygous for a 7 base pair StAR deletion causing a frameshift. No mutations were found in Patient 3, suggesting a novel disease. CONCLUSIONS: Although genetic disorders of steroidogenesis typically present in the first month of life, some defects, especially those in StAR, can present in mid-infancy, when adrenal hyperplasias are rarely considered. Adrenal insufficiency is a subtle disorder that may cause cardiovascular collapse, causing unexplained infant death that resembles SIDS.

Adrenal Hyperplasia, Congenital↗

PubMed1996

Results of bypass to the popliteal and tibial arteries with alternative sources of autogenous vein.

PURPOSE: The goal of an all-autogenous policy for infrainguinal arterial bypass requires that many bypasses be performed with alternative autogenous veins (AAV) because an adequate length of ipsilateral or contralateral greater saphenous vein (GSV) is not available. The durability and efficacy of infrainguinal vein bypasses constructed of venous conduits other than a single segment of greater saphenous vein (SSGSV) is, however, questioned. METHODS: AAV and GSV bypasses were reviewed from 1980 through 1994. Patients who required bypass to the popliteal or a tibial artery were compared for vascular surgical history and vascular disease risk factors and life-table survival. AAV and SSGSV procedures were compared for indications for surgery, morbidity and mortality rates, limb salvage rates in patients who underwent surgery for limb-salvage indications, subsequent need for revision, and life-table-assisted primary patency. RESULTS: Nine hundred nineteen autogenous vein bypasses were performed to the popliteal or a tibial artery--187 (20%) with AAVs, including whole or partial arm vein conduits in 144 grafts (77%). One hundred fourteen AAVs (61%) required vein splicing. The mortality rate was 2% for SSGSV bypasses and 1% for AAV bypasses. The morbidity rate was higher for GSV surgery as a result of increased wound complications (11% vs 5%; p=0.02). Sixty-seven percent of patients with AAV bypass extremities had undergone previous ipsilateral arterial surgery, compared with 20% of patients with SSGSV bypasses (p0.0005). AAV bypasses were more likely to be to a tibial artery (71% vs 45%; p<0.0001). Twelve percent of SSGSV and 15% of AAV popliteal bypasses required revision (p=NS). The 5-year assisted primary patencies were 82%, 77%, and 63%, with limb salvage rates of 91%, 86%, and 74% for ipsilateral SSGSV, contralateral SSGSV, and AAV femoropopliteal bypasses, respectively. Twelve percent of SSGSV and 30% of AAV tibial bypasses required revision (p=0.0001). The 5-year assisted primary patencies were 74%, 82%, and 72%, with limb salvage rates of 84%, 92% and 78% for ipsilateral SSGSV, contralateral SSGSV, and AAV femorotibial bypasses, respectively. CONCLUSION: AAV bypasses can provide overall results comparable with SSGSV bypasses.

Aged↗