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Origins and complexes: the initiation of DNA replication.

Eukaryotic DNA is organized for replication as multiple replicons. DNA synthesis in each replicon is initiated at an origin of replication. In both budding yeast, Saccharomyces cerevisiae and fission yeast, Schizosaccharomyces pombe, origins contain specific sequences that are essential for initiation, although these differ significantly between the two yeasts with those of S. pombe being more complex then those of S. cerevisiae. However, it is not yet clear whether the replication origins of plants contain specific essential sequences or whether origin sites are determined by features of chromatin structure. In all eukaryotes there are several biochemical events that must take place before initiation can occur. These are the marking of the origins by the origin recognition complex (ORC), the loading onto the origins, in a series of steps, of origin activation factors including the MCM proteins, and the initial denaturation of the double helix to form a replication "bubble". Only then can the enzymes that actually initiate replication, primase and DNA polymerase-alpha, gain access to the template. In many cells this complex series of events occurs only once per cell cycle, ensuring that DNA is not re-replicated within one cycle. However, regulated re-replication of DNA within one cell cycle (DNA endoreduplication) is relatively common in plants, indicating that the "once-per-cycle" controls can be overridden.

Cell Cycle↗

Origins of the gonadal artery: embryologic implications.

The gonadal arteries are paired vessels that usually originate from the abdominal aorta at the level of second lumbar vertebra. In 5-20% of cases, the gonadal artery has a high origin (superior to L2) and in 5-6% of cases it originates from the main or accessory renal artery. The latter is referred to here as an aberrant gonadal artery. Ninety-eight kidneys of 50 healthy potential renal transplant donors were prospectively studied by conventional angiography. The renal artery, either main or accessory, was detected and individually injected to highlight their perihilar divisions and possible extrarenal branches. The gonadal arteries were recorded if they originated from the renal arteries. We found that 39% (n = 38) of kidneys had at least one accessory renal artery. In 14 sides (14% of kidneys), the gonadal artery (11 right and 3 left) originated from the renal artery, either main (n = 5) or accessory (n = 9). Ten out of 14 kidneys with an aberrant gonadal artery had an associated accessory renal artery. In nine cases, the gonadal artery originated from the accessory renal artery, and in one case, although it originated from the main renal artery, the same kidney had an accessory arterial supply. The results of this study demonstrate that aberrant gonadal arteries tend to originate from kidneys that possess an accessory arterial supply. We hypothesize that aberrancies of the gonadal artery are a part of a common embryologic error resulting in the persistence of the future accessory renal arteries. We believe that this study is the first to hypothesize and study such an association with these arterial anomalies of the renal pedicle.

Adult↗

Electrocardiographic inverse solution for ectopic origin of excitation in two-dimensional propagation model.

Inverse calculations were examined that sought the origin of a cardiac ectopic excitation sequence. Cardiac anatomy and its geometric relationships to sites on the body surface were adapted from human cross-sectional images to form a two-dimensional model, which included ventricular muscle and a primitive conduction system. The surrounding volume conductor was modelled in a simplified way as unbounded, homogeneous and isotropic. In a series of tests, one ectopic origin was designated the 'true' origin. The ECG for this true origin was compared to ECGs for 197 ectopic 'trial' origins, and differences between the wave forms for true versus trial origins were determined. Core issues were the magnitudes of changes in ECG wave forms as a function of the site of origin, whether these changes were sufficient to imply uniqueness, and what spatial resolution might be expected, in the presence of realistic noise levels. For a noise level of 10 microV RMS, the origin of excitation was localised to a single region of the muscle using one wave form from the body surface, with a resolution of 10 mm. The resolution was not improved significantly with a second electrode on the body surface, but was substantially improved with an endocardial electrode.

Algorithms↗

Traumatic epidural haematomas of nonarterial origin: analysis of 30 consecutive cases.

BACKGROUND: The purpose was to analyse the clinical and radiological findings, and management approaches used in 30 consecutive cases of traumatic epidural haematoma of nonarterial origin treated at one centre. METHOD: Medical records for 30 patients surgically treated for epidural haematoma of nonarterial origin between 1997 and 2003 were reviewed. Epidural haematoma of nonarterial origin was diagnosed based on computed tomography (CT) and the bleeding source was confirmed intra-operatively. Admission status, outcome, fracture location, haematoma location/size/volume, and additional intracranial pathology were among the data noted. Two groups were formed for analysis: venous sinus bleeding (group 1) and other venous sources (group 2). FINDINGS: The 30 cases accounted for 25% of the total number of traumatic epidural haematomas (n = 120) treated during the same period. The epidural haematomas of nonarterial origin locations were transverse sigmoid sinus (n = 11; 36.7%), superior sagittal sinus (n = 6; 20%), venous lakes (n = 5; 16.6%), diploë (n = 5; 0.16%), arachnoid granulations (n = 2; 6.7%), petrosal sinus (n = 1; 3.3%). There were 12 postoperative complications in 9 patients: recurrence (n = 4; 13.3% of the 30 total), pneumonia (n = 4; 13.3%), meningitis (n = 2; 6.7%), hydrocephalus (n = 1; 3.3%) and subdural effusion (n = 1; 3.3%). All recurrence cases were re-explored. Six (20%) patients died. Glasgow Outcome Scale (GOS) scores (mean follow-up 13.3 +/- 7.8 months) revealed 22 (73.3%) patients with favourable results (GOS 4-5) and 8 (26.7%) had poor results (GOS 1-3). CONCLUSIONS: Cases of epidural haematoma of nonarterial origin differ from the more common arterial-origin epidural haematomas with respect to lesion location, surgical planning, postoperative complications, and outcome. Epidural haematoma of nonarterial origin should be suspected if preoperative CT shows a haematoma overlying a dural venous sinus or in the posterior fossa and convexity. The sinus-origin group had a high frequency of fractures which crossed the sinuses, and this might be diagnostically and surgically useful in such cases.

Adolescent↗

Ventricular activation during ventricular endocardial pacing. II. Role of pace-mapping to localize origin of ventricular tachycardia.

Intraoperative pace-mapping has been proposed as a method of identifying the origin of ventricular tachycardia; however, both epicardial activation and electrocardiographic configuration have limitations in localizing the origin of ventricular tachycardia. Because most ventricular tachycardias associated with ischemic heart disease appear to arise near the endocardium, this study evaluated the ability of bipolar catheter endocardial pacing at or near the endocardial site of origin of spontaneous ventricular tachycardia to mimic the QRS configuration of the spontaneous tachycardia. Twelve patients were studied who had ventricular tachycardia whose origin was determined with catheter endocardial mapping. Three patients had ventricular tachycardia with two distinct configurations. The electrocardiogram of ventricular tachycardia was compared with the electrocardiogram produced by pacing at the site of origin (10 patients) and at multiple (two to nine) additional sites in 8 patients. It was observed that (1) pacing at the known site of origin of ventricular tachycardia produced an electrocardiogram and activation sequence similar to those produced by the ventricular tachycardia; (2) pacing at sites in close proximity to the site of origin of ventricular tachycardia produced either a similar or a grossly different electrocardiographic pattern from that during ventricular tachycardia. It is concluded that catheter endocardial pace-mapping (1) is a corroborative method of identifying the origin of ventricular tachycardia; (2) may be useful in patients with noninducible ventricular tachycardia or rapid ventricular tachycardia who cannot undergo catheter or intraoperative mapping; and (3) is neither easier, more accurate nor quicker than direct localization by mapping during ventricular tachycardia.

Adult↗

Cell-cycle control of a cloned chromosomal origin of replication from Caulobacter crescentus.

Caulobacter crescentus cell division is asymmetric and yields distinct swarmer cell and stalked cell progeny. Only the stalked cell initiates chromosomal replication, and the swarmer cell must differentiate into a stalked cell before chromosomal DNA replication can occur. In an effort to understand this developmental control of replication, we employed pulsed-field gel electrophoresis to localize and to isolate the chromosomal origin of replication. The C. crescentus homologues of several Escherichia coli genes are adjacent to the origin in the physical order hemE, origin, dnaA and dnaK,J. Deletion analysis reveals that the minimal sequence requirement for autonomous replication is greater than 430 base-pairs, but less than 720 base-pairs. A plasmid, whose replication relies only on DNA from the C. crescentus origin of replication, has a distinct temporal pattern of DNA synthesis that resembles that of the bona fide C. crescentus chromosome. This implies that cis-acting replication control elements are closely linked to this origin of replication. This DNA contains sequence motifs that are common to other bacterial origins, such as five DnaA boxes, an E. coli-like 13-mer, and an exceptional A + T-rich region. Point mutations in one of the DnaA boxes abolish replication in C. crescentus. This origin also possesses three additional motifs that are unique to the C. crescentus origin of replication: seven 8-mer (GGCCTTCC) motifs, nine 8-mer (AAGCCCGG) motifs, and five 9-mer (GTTAA-n7-TTAA) motifs are present. The latter two motifs are implicated in essential C. crescentus replication functions, because they are contained within specific deletions that abolish replication.

Bacterial Proteins↗

GABAA receptor beta3 subunit gene-deficient heterozygous mice show parent-of-origin and gender-related differences in beta3 subunit levels, EEG, and behavior.

The homozygous knockout mouse for the beta3 subunit of the GABAA receptor has been proposed as a model for the neurodevelopmental disorder, Angelman syndrome, based on phenotypic similarities of craniofacial abnormalities, cognitive defects, hyperactivity, motor incoordination, disturbed rest-activity cycles, and epilepsy. Since most children with Angelman syndrome are autosomal heterozygotes of maternal origin, apparently through genomic imprinting, we used gabrb3-deficient heterozygote mice of defined parental origin to investigate whether this phenotype is also maternally imprinted in mouse. Whole brain extracts showed greatly reduced beta3 subunit levels in male mice of maternal origin but not in male mice of paternal origin. Females of both parental origin showed greatly reduced beta3 subunit levels. Heterozygotes did not exhibit hyperactive circling behavior, convulsions, or electrographically recorded seizures. EEGs showed qualitative differences among heterozygotes, with male mice of maternal origin demonstrating more abnormalities including increased theta activity. Ethosuximide inhibited theta bursts, suggesting an alteration in the thalamocortical relay. Carbamazepine induced EEG slowing in males and EEG acceleration in females, with a larger effect in paternal-origin heterozygotes. Evidence thus suggests both parent-of-origin and gender-related components in developmental regulation of beta3 expression, in particular, that the maternally-derived male heterozygote may carry a developmental modification resulting in less beta3 protein, which may reflect partial genomic imprinting of the gabrb3 gene in mice.

Angelman Syndrome↗

Non-genital tract metastases to the ovaries presented as ovarian tumors in Sweden 1990-2003: occurrence, origin and survival compared to ovarian cancer.

OBJECTIVE: The aim of this register study was to determine occurrence of non-genital ovarian metastasis detected by gynecologic surgery presented as ovarian neoplasm in Sweden from 1 January 1990 to 31 December 2003. Origin of metastases and time of detection in relation to surgery were recorded. Age at diagnosis, survival for ovarian metastasis compared to ovarian cancer and prognostic factors were evaluated. METHODS: Utilizing the population-based Swedish In-Patient Registry, Cancer Registry and Causes of Death Registry, we identified 255 cases with non-genital tract metastases to the ovaries detected at gynecological surgery. During the study period, 10,955 newly diagnosed cases of ovarian cancer were reported to the Swedish Cancer Registry. RESULTS: The proportion of ovarian metastases detected at surgery of all ovarian neoplasm increased from 1.7% to 3.0% during the study period. The patients with ovarian metastasis of non-GI origin were younger than patients with primary ovarian cancer. The most common primary diseases were breast cancer (29%), colon cancer (27%) and gastric cancer (16%). Ovarian metastasis of GI origin preceded primary diagnosis in 51% of patients but for women with disease of non-GI origin the primary diagnosis was made in 18% of patients after surgery. Five-year survival for patients with ovarian metastasis of GI origin was 11% and it was 24% if metastases were of non-GI origin. Five-year survival for women with ovarian metastases from breast cancer was 26%. In a multivariate analysis, GI surgery at primary surgery for ovarian metastasis was unfavorable prognostic factor. Diagnosis of primary disease known before surgery, primary disease of non-GI or unknown origin and operation at university hospital all had favorable prognostic impact for overall survival. CONCLUSIONS: Detection of non-genital ovarian metastasis at gynecologic surgery is associated with poor prognosis, and prognosis is worse in tumors with GI origin and if the primary is not detected prior to surgery. The results indicate that a thorough patient evaluation is very important before surgery for suspected ovarian neoplasm.

Adolescent↗

Different implantation rates after transfers of cryopreserved embryos originating from donated oocytes or from regular in vitro fertilization.

Most oocyte donation programs have experienced higher pregnancy rates than usually seen in regular in vitro fertilization (IVF), suggesting that the quality of either the oocytes or the endometrium is superior. To clarify this issue we analyzed the results of transfers of 136 cryopreserved embryos originating either from donated oocytes (18 transfers) or from regular IVF (118 transfers). Transfers of embryos originating from donated oocytes took place after administrating oral estradiol (E2) valerate and vaginal micronized progesterone (P) following a regimen designed to mimic the serum levels of E2 and P observed during the menstrual cycle. Transfers of embryos originating from regular IVF took place either in the natural cycle (53 transfers) or after suppressing ovarian function with a single injection of a gonadotropin-releasing hormone agonist (GnRH-a), Decapeptyl-Retard 3.75 mg, and administering the same hormone replacement regimen (E2/P) used in oocyte donation (65 transfers). Eighteen transfers involving 24 embryos originating from donated oocytes were affected, resulting in six pregnancies (4 ongoing). The ongoing pregnancy rate per transfer was 22%. Seventy-nine embryos originating from regular IVF were transferred (53 transfers) in the natural cycle resulting in six pregnancies (2 ongoing). One hundred three other embryos originating from regular IVF were transferred (65 transfers) after administration of GnRH-a and E2/P resulting in four pregnancies. The pregnancy rate after transfers of embryos originating from regular IVF was 9% per transfer. This was significantly less than the pregnancy rate of 33% per transfer seen after the transfers of embryos originating from donated oocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pleistocene effects on the European freshwater fish fauna: double origin of the cobitid genus Sabanejewia in the Danube basin (Osteichthyes: Cobitidae).

Biogeographical hypotheses of European freshwater fishes were inferred using phylogeographic analysis of the complete cytochrome b and ATP synthase 8 and 6 mitochondrial genes (1982bp). To test the relative importance of drainage origin versus Pleistocene glaciations in the origin of primary freshwater fishes in Europe, we reconstructed the phylogenetic relationships of the genus Sabanejewia which is distributed in European waters. The phylogenetic relationships recovered for the genus Sabanejewia (n=75) provide support for the monophyly of six main evolutionary mtDNA lineages: Sabanejewia larvata, Sabanejewia romanica, Sabanejewia aurata/Sabanejewia caucasica, Sabanejewia kubanica, Sabanejewia baltica, and the Danubian-Balkanian complex. The Caucasian-Caspian mtDNA lineages, S. kubanica, S. aurata/S. caucasica, and the Northern European S. baltica represents the sister group of the Danubian-Balkanian complex mtDNAclade, supporting a Caucasian-Northern European origin of most of mtDNA lineages of the Central European freshwater fish fauna. The mtDNA divergence observed between the Danubian Sabanejewia species is too dissimilar to support their contemporary origin. Rather, the mtDNA data suggest that the Danubian Sabanejewia lineages most likely have a double origin, indicating that the European Sabanejewia lineages have experienced different historical processes for the following reasons. First, the origin of the S. larvata and S. romanica mtDNA clades predates the origin of the Danubian-Balkanian complex, and our results showed that the completion of the Alps and the origin of the Danube drainage seem to have promoted the speciation of the earliest Sabanejewia clades in the Miocene. Second, small genetic distances and the geographical pattern found within the Danubian-Balkanian complex clade indicate that the lineages included in this clade spread recently across the Danube and Greek river drainages. The inclusion of the S. balcanica species within all mtDNA lineages suggests that cyclical cold periods during the Pleistocene glaciations have favoured its rapid expansion and genetic homogenisation across Central European and Greek waters.

Animals↗

Mutations in direct repeat sequences and in a conserved sequence adjacent to the repeats result in a defective replication origin in plasmid R6K.

Plasmid pMM3 is a pBR322 derivative carrying the gamma origin of replication of the naturally occurring plasmid R6K. We have produced a gamma-origin mutant bank of this plasmid using the single-strand-specific mutagen sodium bisulfite. Members of this bank contain single or multiple mutations in the seven direct repeats and the flanking sequences in the gamma origin. Three mutants with defective gamma origins have been isolated from this mutant bank. Two of these direct repeat mutants, gamma 117 and gamma 120, are unable to replicate and also have lost the ability to bind the R6K initiation protein pi in vitro at one of the seven 22-base-pair direct repeats within their respective origins. Precise deletion of the damaged repeat of either of these mutants restores origin function, suggesting that the primary defect of these mutants involves a disruption of the normal spacing of pi binding and flanking sequences within the gamma origin. The third mutant, gamma 111, binds pi normally but replicates at a greatly reduced copy number due to a mutation near the seventh repeat. This mutation falls within a short sequence that appears to be conserved among a number of other plasmids that contain direct repeats within their origins of replication.

Base Sequence↗

Negative control of plasmid R6K replication: possible role of intermolecular coupling of replication origins.

The gamma origin binding sites of the replication initiator pi protein, composed of seven 22-base-pair (bp) direct repeats and previously shown to be essential for replication of plasmid R6K, can also act as an inhibitor of R6K replication in Escherichia coli cells if provided in trans. Inhibition is dependent upon the ability of these repeats to bind the R6K-encoded pi protein but is not overcome by increasing the intracellular pi level. The insertion of a second repeat cluster in close proximity to the gamma origin also can markedly inhibit replication. The severity of this effect is dependent upon the position, orientation, and number of repeats present in the extra cluster. As few as six extra repeats can result in a completely nonfunctional gamma origin. However, this inactive gamma origin plasmid containing the six extra repeats is functional when placed in a strain that underproduces the wild-type pi protein or when placed in the presence of any of several copy-up mutant pi proteins. On the basis of these observations, we propose that the nucleoprotein structures formed by the binding of pi protein to the seven 22-bp direct repeats at the gamma origin are capable of coupling with each other in vivo and that replication initiation is prevented at such coupled origins. In support of this model of replication control, we demonstrate by electron microscopy analysis that the pi protein has the ability to associate two DNA molecules containing gamma origin sequences and also show that pi enhances the DNA ligase-catalyzed multimerization of a DNA fragment containing the gamma origin.

Bacterial Proteins↗

Initiation preference at a yeast origin of replication.

Replication origins in the yeast Saccharomyces cerevisiae are identified as autonomous replication sequence (ARS) elements. To examine the effect of origin density on replication initiation, we have analyzed the replication of a plasmid that contains two copies of the same origin, ARS1. The activation of origins and the direction that replication forks move through flanking sequences can be physically determined by analyzing replication intermediates on two-dimensional agarose gels. We find that only one of the two identical ARSs on the plasmid initiates replication on any given plasmid molecule; that is, this close spacing of ARSs results in an apparent interference between the potential origins. Moreover, in the particular plasmid that we constructed, one of the two identical copies of ARS1 is used four times more frequently than the other one. These results show that the plasmid context is critical for determining the preferred origin. This origin preference is also exhibited when the tandem copies of ARS1 are introduced into a yeast chromosome. The sequences responsible for establishing the origin preference have been identified by deletion analysis and are found to reside in a portion of the yeast URA3 gene.

Chromosomes↗

A procedure for use in estimating human exposure to particulate matter of ambient origin.

Modern epidemiology has shown that fluctuations of mortality data are statistically significantly correlated with fluctuations of ambient particulate matter (PM) concentration data. This relation cannot be confounded by exposure to PM of indoor origin because the concentrations of ambient PM are not correlated with concentrations of PM of indoor origin. It has been suggested, given the above understanding, that modern PM exposure measurements and analysis should create separate estimates of exposure to all PM of ambient origin and exposure to all PM of nonambient origin (primarily of indoor origin), and not exposure to total PM. This paper reviews the developments of the form of the general microenvironmental mass balance equation that can be utilized for estimating human exposure to PM of ambient origin and for estimating the portion of total PM exposure that is attributable to nonambient origin PM. The equation is perfectly general and can be applied to conditions of time-varying factors that influence exposure, such as rapidly changing air-exchange rates in a home as doors and windows are opened and closed, and turning on and off air cleaners in a home. It is suggested that this procedure be applied in exposure assessment studies and validated using independent techniques of estimating exposure to PM of ambient origin available in the literature.

Air Pollution↗

Parental origin and phenotype of triploidy in spontaneous abortions: predominance of diandry and association with the partial hydatidiform mole.

The origin of human triploidy is controversial. Early cytogenetic studies found the majority of cases to be paternal in origin; however, recent molecular analyses have challenged these findings, suggesting that digynic triploidy is the most common source of triploidy. To resolve this dispute, we examined 91 cases of human triploid spontaneous abortions to (1) determine the mechanism of origin of the additional haploid set, and (2) assess the effect of origin on the phenotype of the conceptus. Our results indicate that the majority of cases were diandric in origin because of dispermy, whereas the maternally-derived cases mainly originated through errors in meiosis II. Furthermore, our results indicate a complex relationship between phenotype and parental origin: paternally-derived cases predominate among "typical" spontaneous abortions, whereas maternally-derived cases are associated with either early embryonic demise or with relatively late demise involving a well-formed fetus. As the cytogenetic studies relied on analyses of the former type of material and the molecular studies on the latter sources, the discrepancies between the data sets are explained by differences in ascertainment. In studies correlating the origin of the extra haploid set with histological phenotype, we observed an association between paternal-but not maternal-triploidy and the development of partial hydatidiform moles. However, only a proportion of paternally derived cases developed a partial molar phenotype, indicating that the mere presence of two paternal genomes is not sufficient for molar development.

Abortion, Spontaneous↗

Posttransplantation lymphoproliferative disorders in solid organ recipients are predominantly aggressive tumors of host origin.

Patients immunosuppressed after organ transplantation have an increased frequency of lymphoproliferative disorders, known as posttransplantation lymphoproliferative disorders (PTLDs). In recipients of bone marrow allografts. PTLDs are often of donor origin. In only a few cases of lymphoma arising in solid-organ transplant recipients has the origin from host or donor lymphocytes been established. The authors have analyzed 11 cases of PTLD from Massachusetts General Hospital, arising in seven male and four female patients, aged 8 to 63, five with renal, four with cardiac, and two with hepatic allografts. Using the polymerase chain reaction (PCR) to investigate genetic polymorphism at the D4S174 locus on chromosome 4, the Rb1.20 locus on chromosome 13, and the D19S178 locus on chromosome 19, only one tumor (previously reported) was of donor origin, whereas 10 were of host origin. Follow-up revealed that six patients died of PTLD, one was alive with recurrent PTLD, and four were alive and well or had died of other causes, including the patient with donor-origin PTLD. Based on these cases and on a review of previously reported cases, the authors conclude that the majority of PTLDs in solid organ recipients are of host origin. There appears to be a trend toward a greater likelihood of persistent or recurrent PTLD among solid organ recipients with host-origin tumors than among those with donor-origin tumor.

Adolescent↗

Effects of seed origin and sowing time on timing of height growth cessation of Betula pendula seedlings.

We studied the effects of seed origin and sowing time on height development and timing of height growth cessation of first-year silver birch (Betula pendula Roth) seedlings in a greenhouse experiment. Seeds of seven origins ranging in latitudes from 58 degrees to 67 degrees N were sown at 1-2-week intervals eight times from May 21 to July 30, 2001. The day/night temperature in the greenhouse was set at 20/10 degrees C, but lighting was natural and day length varied accordingly. Seedling height was measured twice a week. The interaction term between seed origin and sowing date was significant, but the pattern of height development and timing of growth cessation depended systematically on latitude of seed origin and sowing date. As seed origin became increasingly northern, growth cessation began earlier and resulted in shorter growth periods. Later sowing dates delayed growth cessation but also shortened the growth period. Final seedling height systematically decreased with increasingly northern origins and with later sowings. Linear regression analysis predicted timing of growth cessation, night length at growth cessation, length of growth period and final seedling height with high precision when the latitude of seed origin and sowing time were predictor variables. The timing of height growth cessation was determined by the seed origin, night length and developmental stage of the seedlings.

Betula↗

Extradural origin of the posteroinferior cerebellar artery: an anatomic study with histological and radiographic correlation.

OBJECTIVE: The posteroinferior cerebellar artery (PICA) usually arises from the intradural segment of the vertebral artery (VA). The extradural origin of the PICA is infrequent. Its preoperatory identification is important in surgical strategy during the exposure of the VA. METHODS: During an anatomic prosection, the VA was exposed at the craniocervical junction in cadaveric adult specimens. The extradural origin of the PICA was encountered bilaterally in one specimen and on one side in a second specimen. An anatomic study with histological and radiographic correlation was performed. RESULTS: Perforating branches originate from the PICA. They supply the middle and inferior third of the olive and the lateral aspect of the medulla. The PICA has cortical branches that lead to the cerebellum. Injury to the PICA can produce an infarction of these neural structures that can be asymptomatic or cause major neurological deficits. Radiographic results obtained using a lateral projection provided the most reliable delineation of the extradural origin of the PICA. When this artery originates at, or posterior to, the posterior aspect of the occipital condyle, an extradural origin is likely. CONCLUSION: Bilateral selective vertebral angiography should be performed with special attention to the relationships of PICA origins before any surgical exposure of the VA at the craniocervical junction, unless magnetic resonance angiography provides this information without question. A thorough understanding of the relative dominance of the VAs and PICAs, the location of the PICA origin, and the collateral circulation of the posterior fossa are prerequisites to surgery in this region. The preoperative identification of an extradural PICA is important in planning surgical strategy and in avoiding complications during operations near the foramen magnum.

Aged↗