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Decreased origin usage and initiation of DNA replication in haploinsufficient HCT116 Ku80+/- cells.

One of the functions of the abundant heterodimeric nuclear protein, Ku (Ku70/Ku80), is its involvement in the initiation of DNA replication through its ability to bind to chromosomal replication origins in a sequence-specific and cell cycle dependent manner. Here, using HCT116 Ku80+/- cells, the effect of Ku80 deficiency on cell cycle progression and origin activation was examined. Western blot analyses revealed a 75% and 36% decrease in the nuclear expression of Ku80 and Ku70, respectively. This was concomitant with a 33% and 40% decrease in chromatin binding of both proteins, respectively. Cell cycle analysis of asynchronous and late G1 synchronized Ku80+/- cells revealed a prolonged G1 phase. Furthermore, these Ku-deficient cells had a 4.5-, 3.4- and 4.3-fold decrease in nascent strand DNA abundance at the lamin B2, beta-globin and c-myc replication origins, respectively. Chromatin immunoprecipitation (ChIP) assays showed that the association of Ku80 with the lamin B2, beta-globin and c-myc origins was decreased by 1.5-, 2.3- and 2.5-fold, respectively, whereas that of Ku70 was similarly decreased (by 2.1-, 1.5- and 1.7-fold, respectively) in Ku80+/- cells. The results indicate that a deficiency of Ku80 resulted in a prolonged G1 phase, as well as decreased Ku binding to and activation of origins of DNA replication.

Animals↗

Detection of anomalous origins of the coronary artery by means of multislice computed tomography.

BACKGROUND: Anomalous origins of the coronary artery are rare, but may cause myocardial ischemia and sudden death. Thus, their reliable identification is crucial for any imaging method that attempts coronary artery visualization and of those available multislice computed tomography (MSCT), which provides excellent spatial resolution, may be the most promising. METHODS AND RESULTS: In consecutive 1,153 patients, MSCT identified 5 patients (0.43 %) with an anomalous origin of the coronary artery. The left circumflex artery (LCX) originated from the right sinus of Valsalva in 1 patient, and the right coronary artery originated from the left sinus of Valsalva and coursed between the aortic root and the pulmonary artery in 3 patients. In 1 patient, MSCT identified the absence of the LCX and high-grade atherosclerotic stenosis in the right coronary artery. CONCLUSION: MSCT can detect the anomalous origin and course of the coronary artery in relation to the great vessels. It is also useful for identifying atherosclerotic coronary artery disease superimposed on the anomalous vascular system.

Aged↗

Nerve origin of the acoustic neuroma.

Two hundred and seventy-one Japanese patients who underwent surgical removal of neuroma from the cerebello-pontine angle using the translabyrinthine approach were retrospectively reviewed in order to investigate the nerve origin on an anatomical basis. In 269 out of the 271 cases, the origin of the neuromas was identified. Among these cases, 84.8 per cent of tumours originated from the inferior vestibular nerve (IVN), followed by the superior vestibular nerve (SVN) (8.9 per cent). Of the 5.6 per cent of tumours arising from the vestibular nerve, however, it could not be determined whether they originated from the SVN or IVN. Two cases of neuromas originating from the facial nerve were seen (0.7 per cent). No neuroma arose from the cochlear nerve. Currently, the diagnosis of acoustic neuromas is best made with Gd-enhanced magnetic resonance imaging (MRI). However, our data indicate that the development of a functional test of the individual IVN can be useful for screening most cases of acoustic neuroma and in facilitating their early diagnosis.

Cerebellar Neoplasms↗

Origin of lumbar spinal roots and their relationship to intervertebral discs: a cadaver and radiological study.

Previous studies on the anatomy of the lumbar spine have not clarified the precise relationship of the origin of the lumbar roots to their corresponding discs or their angulation to the dural sac. We studied 33 cadavers (25 formalin-preserved and eight fresh-frozen) and their radiographs to determine these details. All cadavers showed a gradual decrease in the angle of the nerve root from L1 to S1. The origin of the root was found to be below the corresponding disc for the L1 to L4 roots. In the formalin-preserved cadavers 8% of the L5 roots originated above, 64% below and 28% at the L4/L5 disc. In the fresh cadavers the values were 12.5%, 62.5% and 25%, respectively. For the S1 root 76% originated above and 24% at the L5-S1 disc in the formalin-preserved cadavers and 75% and 25%, respectively, in the fresh cadavers.A herniated disc usually compresses the root before division of the root sleeve. Thus, compression of the thecal sac before the origin of the root sleeve is common for L1 to L5 whereas compression at the root sleeve is common for S1. Our findings are of value in understanding the pathophysiology of prolapse of the disc and in preventing complications during surgery.

Adult↗

Accuracy of abstracts for original research articles in pharmacy journals.

BACKGROUND: Accuracy of abstracts representing original research articles is imperative since these are readily available and biomedical literature readers may not have access to the full-text article. Furthermore, previous reports document discrepancies in published original research abstracts compared with the full-text article. OBJECTIVE: To determine the accuracy of abstracts for original research articles published in nationally represented, widely circulated pharmacy-specific journals (American Journal of Health-System Pharmacy, The Annals of Pharmacotherapy, The Consultant Pharmacist, Hospital Pharmacy, Journal of the American Pharmacists Association, Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy) from June 2001 through May 2002. METHODS: Outcome measures included an omission, defined as data in the abstract not located in the article. In addition, abstracts were considered deficient if these included an omission, inaccurate factual (i.e., qualitative and quantitative) information presented in the abstract that differed from information contained within the text, an inconsistency in following the "Instructions for Authors" for the respective journal, or a discrepancy between the placement of text in the manuscript and a structured abstract. RESULTS: A total of 243 abstracts for original research articles were published in selected journal issues. Evaluation of these abstracts identified 60 (24.7%) abstracts containing omissions; 81 (33.3%) abstracts contained either an omission or inaccuracy. A total of 147 (60.5%) abstracts were classified as deficient. CONCLUSIONS: Results of this analysis demonstrate that improvements are needed within abstracts for original research articles published in pharmacy-specific journals. Authors and peer reviewers should analyze the abstract contents closely to ensure that the abstract accurately represents the full-text article.

Abstracting and Indexing↗

Anomalous origin of the left coronary artery from the right pulmonary artery with intramural aortic trajectory. Clinicosurgical diagnostic implications.

OBJECTIVE: Anomalous origin of the left coronary artery from the right pulmonary artery (AOLCARPA), is a rare entity that is usually associated with other defects. Of the 20 cases of AOLCARPA reported in the literature, 14 (70%) had associations. We describe four patients with AOLCARPA without associated defects, but with a peculiar intramural aortic trajectory. METHODS: Fifty-five patients with anomalous origin of the left coronary artery were operated upon at INCORFMUSP. Four of the patients had the anomalous origin from the right pulmonary artery (RPA) without associated defects but with intramural aortic trajectory. Clinical and laboratory examinations were analyzed, as well as surgical findings. RESULTS: All patients had congestive heart failure (CHF) and 3 also had angina pectoris. Two patients had a murmur of mitral regurgitation, signs of myocardial infarction on the ECG and cardiomegaly. The shortening fraction varied from 9% to 23%. The hemodynamic study confirmed the diagnosis of anomalous origin of the coronary artery, but the intramural trajectory and the origin from the RPA were established only at surgery. In 3 patients, the technique of side-to-side anastomosis was performed with a good outcome. One patient, who underwent end-to-side anastomosis, died 6 months after the surgery. CONCLUSION: Association with other defects usually occurs in the AOLCARPA, and the intramural aortic trajectory is difficult to clinically diagnose but easy to surgically correct.

Adolescent↗

A prospective study of hepatitis B virus markers in patients with chronic HBV infection from Brazilian families of Western and Asian origin.

The purpose of the present study was to determine the frequency of hepatitis B virus (HBV) markers in families of HBsAg-positive patients with chronic liver disease. Serum anti-HBc, HBsAg and anti-HBs were determined by enzyme immunoassay and four subpopulations were considered: genetically related (consanguineous) and non-genetically related (non-consanguineous) Asian subjects and genetically related and non-genetically related Western subjects. A total of 165 and 186 relatives of Asian and Western origin were enrolled, respectively. The occurrence of HBsAg and anti-HBs antibodies was significantly higher (P < 0.0001) in family members of Asian origin (81.8%) than in family members of Western origin (36.5%). HBsAg was also more frequent among brothers (79.6 vs 8.5%; P < 0.0001), children (37.9 vs 3.3%; P < 0.0001) and other family members (33.9 vs 16.7%; P < 0.0007) of Asian than Western origin, respectively. No difference between groups was found for anti-HBs, which was more frequently observed in fathers, spouses and other non-genetic relatives. HBV infection was significantly higher in children of Asian than Western mothers (P < 0.0004). In both ethnic groups, the mothers contributed more to their children's infection than the fathers (P < 0.0001). Furthermore, HBsAg was more frequent among consanguineous members and anti-HBs among non-consanguineous members. These results suggest the occurrence of vertical transmission of HBV among consanguineous members and probably horizontal sexual transmission among non-consanguineous members of a family cluster. Thus, the high occurrence of dissemination of HBV infection characterizes family members as a high-risk group that calls for immunoprophylaxis. Finally, the study showed a high familial aggregation rate for both ethnic groups, 18/19 (94.7%) and 23/26 (88.5%) of the Asian and Western origin, respectively.

Adolescent↗

Fasciola hepatica: the growth and larval productivity of redial generations in Galba truncatula subjected to miracidia differing in their mammalian origin.

Experimental infections of Galba truncatula with 4 isolates of Fasciola hepatica miracidia differing by their mammalian origin (cattle, nutrias, rabbits, or sheep) were carried out to determine if parasite origin had an effect on the number of free rediae, their growth, and their larval productivity in each redia category. The mammalian origin of miracidia had a significant influence on the numbers of free rediae (they were higher in cattle-group snails) and the lengths of rediae (they were lower in rabbit groups). The redia category had also a significant effect on body and pharyngeal measurements. In all groups, the majority of cercariae (55.8-63.2%) were produced by the daughter rediae (R2a rediae) originating from the first mother redia. Compared with the other groups, the mean number of cercariae at day 49 postexposure was twice as high in cattle groups. In contrast, the mean number of daughter rediae produced by each second-appearing mother redia or each R2a redia was higher in the nutria, rabbit, and sheep groups. The mammalian origin of F. hepatica miracidia had an effect on the number of live rediae, their length, and their redial and cercarial productivity.

Animals↗

On the origin and preservation of cumulative record in its struggle for life as a favored term.

This paper offers a case study of the origins, emergence, and evolution of the term cumulative record as the name for the means by which B. F. Skinner brought his behavior under the control of his subject matter. Our methods included on-line searches, reviews of Skinner's publications, and journal codings and counts. The results reveal that the term is not originally attributable to Skinner, but emerged earlier in ordinary language and in another discipline--education. It was not even original to Skinner in print in his own science. Still, the term was once original to him, which we address with additional analyses of his having originated and advanced it. We conclude with a discussion the constraints of our methods, suggestions for future research, and the variable appreciation of technology and terminology in science studies.

Behavior↗

Aneurysm of the distal posterior inferior cerebellar artery originating from the extracranial and extradural vertebral artery.

A 42-year-old woman presented with a ruptured aneurysm of the distal posterior inferior cerebellar artery (PICA), which had a rare extracranial and extradural origin. Medial suboccipital craniectomy and C-1 laminectomy were performed. The aneurysm had adhered to the right cerebellar tonsil, but was successfully clipped without difficulty. Intraoperatively, the PICA origin was recognized in the extracranial and extradural space between the dorsal roots of the C-1 and C-2 nerves. The origin of the PICA from the vertebral artery (VA) may occur at any portion of the VA from the site of penetration of the dura to the vertebrobasilar junction, but an extradural origin is uncommon. A ruptured aneurysm of the PICA branching from the VA at a site proximal to the vertebrobasilar junction and below the foramen magnum may be overlooked by three-vessel angiography if the contrast medium cannot reflux to the contralateral PICA origin.

Adult↗

MDCT of the gonadal veins in females with large pelvic masses: value in differentiating ovarian versus uterine origin.

OBJECTIVE: The objective of our study was to determine the usefulness of recognizing the continuity of the gonadal veins to the pelvic mass to differentiate ovarian versus uterine origin on MDCT in females with a large pelvic mass. MATERIALS AND METHODS: Two radiologists interpreted the MDCT images obtained on a monitor, using paging methods, in 86 female patients with a large pelvic mass (> 8 cm) and 40 patients without an abdominopelvic mass as control subjects. The following issues were recorded using a 5-point scale: visualization of gonadal veins and origin determination based on anatomic continuity. Receiver operating characteristic (ROC) curve analysis was performed, and the interobserver differences were checked with kappa statistics. The maximum diameters of the gonadal veins were also measured. With consensus interpretations, the sensitivity, specificity, and accuracy of ovarian origin determination were calculated. RESULTS: Gonadal veins were shown in more than 70% of the subjects in both the control group and the patients with a mass (hereafter referred to as the "mass group"). There was no significant difference in the diameter of the gonadal veins between the control and mass groups and between patients with an ovarian mass and those with a uterine mass. The values for the area under the ROC curve (A(z)) of the two observers for ovarian origin determination were 0.90 and 0.92. The kappa value was 0.48. The sensitivity, specificity, and accuracy were 83.3%, 87.5%, and 84.9%, respectively. CONCLUSION: Gonadal veins can be shown on MDCT with high consistency; MDCT provides useful information for determining the origin of relatively large pelvic tumors arising in females.

Adult↗

Pulse-spray pharmacomechanical thrombolysis of thrombosed hemodialysis access grafts: long-term experience and comparison of original and current techniques.

OBJECTIVE: Pulse-spray pharmacomechanical thrombolysis is an evolving method for the treatment of vascular occlusions in which a highly concentrated fibrinolytic agent is injected as a high-pressure spray directly into thrombus. The purpose of this retrospective study was to analyze our long-term experience with this technique for the treatment of clotted hemodialysis grafts and to compare the efficacy and safety of the original and current methods. SUBJECTS AND METHODS: Over 6 years, 284 cases of dialysis graft thrombosis were considered suitable for treatment with pulse-spray thrombolysis. The original technique involved the injection of highly concentrated urokinase directly into a clot through two crisscross catheters with multiple side holes. The current technique includes early fragmentation of residual clot with a balloon catheter, intrathrombic injection of heparin, mechanical treatment of a lysis-resistant clot at the arterial anastomosis, and routine administration of aspirin. After thrombolysis, underlying obstructions were treated with balloon angioplasty, atherectomy, or stents. The technical success, immediate clinical success, and frequency of complications for the entire population were analyzed. In addition, the results for 36 cases treated with the original technique were compared with the results for 37 recent cases treated with the current technique. RESULTS: Of 284 cases considered suitable for treatment, thrombolysis was not done in eight cases because the venous anastomosis could not be crossed. Thrombolysis was discontinued in two cases because of extravasation of contrast material. The technical success for all grafts considered for treatment was 96%; 92% of treated grafts remained patent for at least 24 hr. Major complications occurred in 1% of cases, and minor complications occurred in 9% of cases. The clinical efficacies of the original and current techniques were 86% and 92%, respectively. The mean thrombolytic agent infusion time was reduced from 44 +/- 20 min to 23 +/- 13 min (p < .001). The overall procedure time for the recently treated subgroup was 67 +/- 26 min. There was no significant difference in the frequencies of major and minor complications between the treatment subgroups. CONCLUSION: Pulse-spray pharmacomechanical thrombolysis is a reliable, rapid, and safe method for recanalization of occluded dialysis grafts. The current technique has been proven as safe and effective as the original technique but offers the advantage of a significant reduction in the time required for the infusion of thrombolytic agent.

Anastomosis, Surgical↗

Estradiol regulation of the frequency and site of origin of uterine contractions in news.

Five experiments were conducted to study the action of estradiol in regulating the frequency and site of origin of contractions in ewes anesthetized with sodium pentobarbitol. Contractions were observed visually by means of midventral laparotomy. In Exp. 1, the percentage of posterior contractions (contractions originating caudal to external bifurcation) of uterine horns and RNA/DNA declined by 36 to 48 hr after the onset of estrus; estradiol posterior contractions and increased RNA/DNA. In Exp. 2, the frequency of contractions in ovariectomized ewes was maximal (53 +/- 5) at 12 hr after an injection of 45 microgram estradiol and was about double the control value (28 +/- 9). The percentage of posterior contractions was greatest at 18 hr (90 +/- 5) and was almost nine times as great as control values (12 +/- 7). RNA/DNA increased from .26 +/- .07 at 12 hr to .48 +/- .05 at 18 hours. In Exp. 3, estradiol increased the frequency of contractions in ovariectomized ewes (48 +/- 2 vs 32 +/- 3) within 6 hours. Neither phenoxybenzamine nor cycloheximide blocked this estradiol-induced increase. In Exp. 4, estradiol increased the percentage of posterior contractions in ovariectomized ewes at 24 hr (7 +/- 4 vs 78 +/- 12), but not the frequency (24 +/- 5 vs 24 +/- 4). Neither 6-OH dopamine nor reserpine altered the estradiol effect on posterior origination of contractions, although reserpine reduced myometrial concentration (nanogram/milligram DNA) of norepinephrine (205 +/- 31 vs 52 +/- 16 without estradiol and 127 +/- 30 vs 62 +/- 13 with estradiol). In Exp. 5, estradiol increased the percentage of posterior contractions in ovariectomized ewes at 24 hr (8 +/- 4 vs 86 +/- 7), and the increase was blocked by indomethacin. Estradiol increased prostaglandin F (PGF) in endometrium but not in myometrium. Indomethacin reduced PGF in both tissues and blocked the estradiol-induced increase. Anterior portions of the uterus had higher concentrations of PGF than did posterior portions. Estradiol induction of high-frequency uterine contractions is dissociable from estradiol induction of a posterior site of origin of contractions, i.e., time for the two effects to appear in ovariectomized ewes differs and the estrogenic regulation of the site of origin of uterine contractions requires protein synthesis.

Animals↗

Comparative anatomical study of the kidney position in amniotes using the origin of the renal artery as a landmark.

The anatomical relationship between the kidney position and its arterial supply was investigated in 21 mammals, 1 bird, and 3 reptiles (n = 1 for each species) and in 43 human cadavers. The following observations were made. (1) Although the right kidney was located caudal to the left kidney in 29 out of 43 human cadavers (67.4%), the origin of the right renal artery from the aorta was located cranial to the origin of the left renal artery in 36 human cadavers (83.7%). Therefore, the relative positions of the kidneys do not correspond with the relative origins of the renal arteries in humans. (2) Among the mammals that were examined, the position of the kidney and the branching level of the renal artery on the right side were usually cranial to those on the left side. (3) In the bird and most reptiles that were examined, kidneys were typically located in the pelvic region and were supplied by segmental arterial branches. These results suggest that the right kidney and its arterial supply are generally located cranial to the left kidney in phylogeny of mammals. While the presence of a human accessory renal artery in 9 out of 86 sides (10.5%) and a cranial origin of the left renal artery relative to the right renal artery in 7 out of 43 cadavers (16.3%), shows some variation in the arterial supply to the kidneys, the origin of the renal arteries can generally be used as phylogenetic landmarks indicating the relative positions of the kidneys. Hence, from an ontological perspective, the human right kidney may be initially situated cranial to the left kidney during the early stages of development. Thereafter, the human right kidney may shift downwards secondary.

Abdomen↗

Coeliac disease in patients with cerebellar ataxia of unknown origin.

BACKGROUND: Neurological symptoms of unknown origin are common in coeliac disease (CD). Evidence suggests that CD may also contribute to the development of idiopathic late-onset ataxia. AIM: To evaluate the frequency of CD in patients with cerebellar ataxia of unknown origin. METHODS: The medical files of adult patients with the diagnosis of cerebellar ataxia of unknown origin (n=44) were evaluated. Serum gliadin, endomysial, and serum tissue transglutaminase antibodies were used as screening tests for CD. Subjects with positive results were referred to small-bowel biopsy. RESULTS: The frequency of CD was as high as 9.1% in all patients. A thorough interview and review of the patient files indicated alcohol abuse as a cause for cerebellar disease in almost half (45.5%) of our patients. When the cases with alcohol abuse were omitted, the calculated frequency of CD was 16.7% in patients with ataxia of unknown origin. CONCLUSION: CD is a common association with cerebellar disease and the disease should be considered in all patients with ataxia of unknown origin.

Adult↗

The replication origin of the Methylomonas clara plasmid pBE-2.

The Methylomonas clara narrow host range plasmids pBE-2 and pBE-3 belong to the class of plasmids encoding a trans acting replication initiation factor. Characteristically for such plasmids, the sequence of the origin of pBE-2 and pBE-3 contains a number of large direct repeats (8 and a half iterons of 19 bp), which by analogy are putative binding sites of the trans acting replication factor. Several additional features typical for the majority of E. coli plasmids were found in the M. clara origin: These include sequences homologous to the E. coli DnaA-box, sequences resembling E. coli IHF binding-sites, an AT-rich region with short repeats (similar to those repeats of E. coli origins responsible for an initial DNA duplex opening), and an AT-rich bent DNA region containing inverted repeats which have homology to small repeated sequences found in several plasmid origins. In addition, in the M. clara plasmid origin, large potential hairpin structures are present and the sequence of one of these participates in site specific recombination.

Base Sequence↗

Microsurgical anatomy of the extracranial-extradural origin of the posterior inferior cerebellar artery.

OBJECT: The authors describe the microsurgical anatomy of the posterior inferior cerebellar artery (PICA) with an extradural origin and discuss its importance as a common variation. METHODS: The microsurgical anatomy of paired PICAs with an extradural origin were examined. CONCLUSIONS: Five to 20% of PICAs have an extradural origin. In the case described, both PICAs arose extradurally from the third segment of the vertebral artery (VA). Both origins were less than 1 cm proximal to the site at which the VA penetrated the dura, and neither PICA gave rise to extradural branches. Extradurally, the PICAs coursed parallel to the VA and the C-1 nerve and the three structures penetrated the dura together. Intradurally, the PICAs remained lateral and posterior to the brainstem, whereas, in the common PICA configuration, the first segment of the PICA courses anterior to the medulla. Neither PICA sent branches to the anterior brainstem, which is commonly found in PICAs with an intradural origin. There were no soft-tissue or bone anomalies.

Arteries↗

Origins of surface potentials evoked by electrical stimulation of oculomotor nerves: are they related to electrooculographic or electromyographic events?

OBJECT: Evoked potentials elicited by electrical stimulation of the oculomotor nerve and recorded from surface electrodes placed on the skin around the eyeball reportedly originate in the eye and are represented on electrooculograms. Because evoked potentials recorded from surface electrodes are extremely similar to those of extraocular muscles, which are represented on electromyograms, the authors investigated the true origin of these potentials. METHODS: Evoked potentials elicited by electrical stimulation of the canine oculomotor nerve were recorded from surface electrodes placed on the skin around the eyeball. A thread sutured to the center of the cornea was pulled and the potentials that were evoked during the resultant eye movement were recorded. These potentials were confirmed to originate in the eye and to be represented on electrooculograms because their waveforms were unaffected by the administration of muscle relaxant. To eliminate the influence of this source, the retina, a main origin of standing potentials of the eyeball, was removed. This resulted in the disappearance of electrooculography (EOG) waves elicited by eye movement. Surface potentials elicited by oculomotor nerve stimulation were the same before and after removal of the retina. Again the oculomotor nerve was electrically stimulated and electromyography (EMG) response of the extraocular muscles was recorded at the same time that potentials were recorded from the surface electrodes. In their peak latencies, amplitudes, and waveforms, the evoked potentials obtained from surface electrodes were almost identical to EMG responses of extraocular muscles. CONCLUSIONS: Evoked potentials elicited by electrical stimulation of the oculomotor nerves and obtained from surface electrodes originated from EMG responses of extraocular muscles. These evoked potentials do not derive from the eye.

Abducens Nerve↗