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PubMed1987

Functional anatomy of the alar ligaments.

Nineteen upper cervical spine specimens were dissected to examine the macroscopic and functional anatomy of alar ligaments. They are on both sides, symmetrically placed, approximately 10-13 mm long and elliptical in cross-section 3 X 6 mm in diameter. The fiber orientation is dependent on the height of dens axis, mostly in the cranial caudal direction. In 12 specimens there was a ligamentous connection between dens and lateral mass of the atlas as a part of the alar ligament. In 2 specimens anterior atlanto-dental ligament was identified. The computerized tomographic (CT) images can clearly show alar ligaments in axial, coronal, and sagittal planes. The ligaments limit the axial rotation in the occipito-atlanto-axial complex (to the right by left alar and vice versa) as well as in side bending. The ligament is most stretched, and consequently most vulnerable, when the head is rotated and in addition flexed. This mechanism, common in whiplash injuries, could lead to irreversible overstretching or rupture of the ligaments especially as the ligaments consist of mainly collagen fibers.

Adult↗
PubMed1997

Unilateral posterior atlantoaxial transarticular screw fixation.

Bilateral posterior C 1-2 transfacet screw placement with associated posterior bone graft wiring is the accepted treatment for patients with atlantoaxial instability. This technique was modified to treat 19 patients with atlantoaxial instability and unilateral anomalies that prevented placement of a screw across the C1-2 facet. In these cases, a single contralateral transarticular screw was placed in conjunction with interspinous bone graft wiring to avoid neural or vertebral artery injury and to provide C1-2 stability. Postoperatively, all 19 patients were placed in Philadelphia collars (mean immobilization 8 weeks, range 6-12 weeks). Unilateral C1-2 facet screw fixation was needed for the following reasons: a high-riding transverse foramen of the C-2 vertebra present in 13 patients (left side in eight, right side in five), poor screw purchase in two (left side in both), screw malposition in one (left side), severe degenerative arthritis in one (right side), neurofibroma in one (right side), and fracture of the C-1 lateral mass in one (left side). Six weeks postsurgery, one patient presented with a broken screw and required occipitocervical fusion with a Steinmann pin and wire cable from the occiput to C-3 to achieve solid fusion. Solid fusions were achieved in the other 18 patients (mean follow-up period 31 months, range 14-54 months); there was no delayed screw breakage, wire breakage, or spinal instability. There were no operative or postoperative neurological or vascular complications. The authors' experience demonstrates that unilateral C1-2 facet screw fixation with interspinous bone graft wiring is an excellent alternative in the treatment of atlantoaxial instability when bilateral screw fixation is contraindicated.

Adult↗
PubMed1998

Posterior atlantoaxial facet screw fixation in rheumatoid arthritis.

OBJECT: This retrospective review was conducted to determine the efficacy of transarticular screw fixation in a group of patients who were treated for rheumatoid atlantoaxial instability. METHODS: Thirty-six patients (mean age 63 years) with rheumatoid atlantoaxial instability were treated with posterior atlantoaxial transarticular screw fixation supplemented with an interspinous C1-2 strut graft-cable construct to provide immediate three-point fixation to facilitate bone fusion. Previous attempts at fusions by using bone grafting with wire fixation at other institutions had failed in six of these patients. Six patients underwent transoral odontoid resections for removal of large irreducible pannus as a first-stage procedure, which was followed within 2 to 3 days by the posterior procedure. Postoperatively, 33 patients were placed in hard cervical collars and three required halo vests because of severe osteoporosis. Of eight patients categorized as Ranawat Class II preoperatively, all eight returned to normal after surgery; of eight patients in Ranawat Class III-A preoperatively, four improved to Class II and four remained unchanged. All 20 patients classified as Ranawat Class I preoperatively recovered completely. Pain decreased or resolved in all patients, and there were no complications related to instrumentation. At follow-up review (mean 2 years), 33 patients (92%) had solid bone fusions, and three (8%) had stable fibrous unions. CONCLUSIONS: Posterior atlantoaxial transarticular screw fixation provides a good surgical alternative for the management of patients with rheumatoid atlantoaxial instability. This technique provides immediate three-point rigid fixation of the C1-2 region, thus obviating the need for halo vest immobilization in most cases.

Adult↗
PubMed1995

A study of radiologic imaging techniques and airway grading to predict a difficult endotracheal intubation.

STUDY OBJECTIVES: To study whether a detailed radiographic examination of neck and upper airway can help identify normal looking patients in whom endotracheal intubation may be difficult; determine whether such parameters as identified by magnetic resonance imaging (MRI) can also be identified in a soft tissue radiograph; and to study the correlation between oropharyngeal appearance, based on Mallampati's classification, and laryngoscopic findings in a large number of patients requiring endotracheal intubation. DESIGN: Prospective. SETTING: University medical center. PATIENTS: 20 adult patients in whom an unanticipated difficult endotracheal intubation was encountered, and a control group of 20 patients in whom endotracheal intubation was easily accomplished. INTERVENTIONS: Difficult-to-intubate patients were identified according to prospectively established criteria. Control subjects, in whom the trachea was easily intubated, were matched for age, gender, height, weight, and oropharyngeal appearance. MEASUREMENTS AND MAIN RESULTS: In all 40 study patients, a soft tissue radiograph and an MRI scan of the neck were obtained. We measured 21 parameters from both radiographic studies. There were no significant differences between the two groups in 20 of 21 measured parameters on MRI scans and soft tissue radiographs. Only one measurement--the distance between the uppermost visible part of the airway and the posterior pharyngeal wall (measured from MRI scans only)--between the two groups achieved statistical significance. The values recorded from MRI and soft tissue radiographs were not significantly different. Airway grading system first suggested by Mallampati had a fair correlation with laryngoscopy findings associated with a difficult endotracheal intubation. CONCLUSIONS: No significant difference between the two groups could be identified on soft tissue radiography or MRI scans.

Adult↗
PubMedDate not supplied

Surgical management of atlantoaxial subluxation in 23 dogs.

Twenty-eight surgical procedures were performed in 23 dogs with atlantoaxial subluxation. Dorsal stabilization in seven dogs resulted in two recoveries and five failures of fixation. Ventral decompression and stabilization in 18 dogs resulted in eight recoveries and four failures of fixation. Six dogs died or were euthanatized within 7 days of ventral stabilization. Using either technique, four of seven nonambulatory dogs recovered.

Animals↗
PubMed1991

[Contrast transfer function of the visual system].

Visually evoked potentials were used to determine the spatial contrast response function of the visual system and the visual acuity of the pigeon. The spatial contrast response describes the relationship between the contrast in a pattern of vertical stripes, whose luminance is a function of position, and the amplitude of the visually evoked response at various spatial frequencies for a given temporal frequency (pattern reversal frequency); it indicates how particular spatial frequencies are attenuated in the visual system. The visually evoked responses were recorded using monopolar stainless steel electrodes inserted into the stratum griseum superficiale of the optic tectum; the depth of penetration was determined on the basis of a stereotactic atlas. The stimulus patterns were generated on a video monitor placed 75 cm in front of the animal's eye perpendicular to the optic axis. The spatial contrast response function measured at 10% contrast and 0.5 Hz reversal frequency shows a peak at a spatial frequency of 0.5 c/deg, corresponding to 1 degree of visual angle, and decreases progressively at higher spatial frequencies. The high-frequency limit (cut-off frequency) for resolution of sinusoidal gratings, estimated from the contrast response function, is 15.5 c/deg, corresponding to a visual acuity of 1.9 min of arc.

Animals↗
PubMedDate not supplied

Narrow axis: an inherited anomaly of the second cervical vertebra in the rabbit.

Narrow axis, an inherited anomaly resulting in a marked narrowing of the second cervical vertebra, has been observed in strain X/J rabbits. This condition is first recognizable on X rays at 32-33 days gestation. For size comparisons 21 measurements of the first five cervical vertebrae were taken on the skeletons of each of 14 strain X/J animals (7 normal and 7 with narrow axis) and 14 IIIC/J animals for control at two months of age and 27 strain X/J (11 normal and 16 narrow axis) and 14 strain IIIC/J at seven months of age. The primary effect appeared to be a premature fusion of the centrum with its neural arches. Expression is variable. The effect on the posterior articulation of the atlas appeared to be secondary and adaptive. The other cervical vertebrae and the foramen magnum were relatively unaffected. In the 20-year period encompassed in this report, X rays of 3244 rabbits were used for genetic analysis. Inheritance appears to be due to a single autosomal recessive gene with incomplete penetrance. The condition is neither sex-linked nor sex-limited. We propose the symbol nx for the gene responsible for narrow axis in the rabbit.

Animals↗
PubMed2026

A Spatiotemporal Atlas of the Androgen Receptor Proximal Interactome.

Androgen receptor-interacting proteins (AR-IPs) number close to 1,000, yet their organization across subcellular space and time remains uncharted. Proximity labeling identifies direct partners and neighboring proteins, thereby expanding AR-IPs to AR-proximal interacting proteins (AR-PIPs). Using proximity labeling quantitative mass spectrometry (PL-qMS), we construct a spatiotemporal atlas of the cytosolic, microsomal, and nuclear compartments in LNCaP prostate tumor cells. PL-qMS recovered 82.2% of the known AR-interactome in extranuclear compartments and 84.2% in the nucleus, identifying 4,751 AR-PIPs that remodel across an androgen time course. The retromer formed an androgen-sensitive AR-proximal interaction network (AR-PIN) verified by proximity ligation assays (PLAs). Moreover, partial VPS26A disruption attenuated androgen-regulated transcription and mislocalized the AR coactivator TMF1, defining a retromer-AR-TMF1 axis. In the nucleus, AR-PINs recover 100% of the Launonen 2021 ChIP-SICAP chromatome and reveal a PLA-verified translation-to-transcription handoff involving eIF4G and 4E-BP1. This spatiotemporal atlas provides a proximal framework for probing AR function in cells.

Journal Article↗
PubMedDate not supplied

Hippocampal atrophy in persons with age-associated memory impairment: volumetry within a common space.

OBJECTIVE: The objective of this study is to demonstrate the assessment of hippocampal atrophy within a standard brain atlas for persons with age-associated memory impairment (AAMI) compared with cognitively intact elderly. METHODS: High-resolution three-dimensional (3D) brain magnetic resonance imaging (MRI) was performed on 20 nondemented persons: 10 had AAMI and 10 were normal elderly. Scans were aligned to a common atlas template to control for errors due to variable brain size and orientation as well as facilitating communication of results across centers. Manual outlining every 1 mm with volumes determined for both the hippocampal head and body was accomplished after coronal resampling perpendicular to the long axis of the hippocampus. RESULTS: Subject groups were similar in age, sex ratios, and educational achievement. The AAMI group had significantly lower volumes for the right hippocampus and hippocampal head (p =.02) compared with controls. CONCLUSION: A growing body of work suggests the right hippocampal head as an early site of atrophy in early memory impairment. Subtle atrophic changes are detectable within a common atlas template allowing imaging assessment across centers.

Aged↗
PubMed2002

Surface-based atlases of cerebellar cortex in the human, macaque, and mouse.

This study describes surface reconstructions and associated flat maps that represent the highly convoluted shape of cerebellar cortex in three species: human, macaque, and mouse. The reconstructions were based on high-resolution structural MRI data obtained from other laboratories. The surface areas determined for the fiducial reconstructions are about 600 cm(2) for the human, 60 cm(2) for the macaque, and 0.8 cm(2) for the mouse. As expected from the ribbon-like pattern of cerebellar folding, the cerebellar flat maps are elongated along the axis parallel to the midline. However, the degree of elongation varies markedly across species. The macaque flat map is many times longer than its mean width, whereas the mouse flat map is only slightly elongated and the human map is intermediate in its aspect ratio. These cerebellar atlases, along with associated software for visualization and for mapping experimental data onto the atlas, are freely available to the neuroscience community (see http:/brainmap.wustl.edu).

Animals↗
PubMed2026

Single-cell multimodal profiling of pan-cancer cell lines uncovers gene regulatory principles underlying intrinsic cell states and environmental features.

Cancer arises from genetic and epigenetic alterations that reshape chromatin, transcriptional regulation, and malignant cell states. To chart cancer-intrinsic regulatory programs, we build a pan-cancer single-cell atlas of 60 cancer cell lines spanning 16 tissue origins and 20 cancer types, comprising 240,957 snRNA-seq and 223,347 snATAC-seq profiles. Integrative analyses reveal cell-state heterogeneity, core gene-regulatory networks, and a conserved EMT axis transcending tissue of origin; copy-number analysis identifies transcription factor amplification and hyperactivation as drivers of state reprogramming. Comparing cutaneous melanoma with acral melanoma, a rare subtype underrepresented in previous studies, uncovers a universal inflammation-suppressive program in acral and an inflamed landscape in cutaneous melanoma, with JAK-STAT activity as the central discriminator. Integrating data across models and patient cohorts links tumor-intrinsic regulation to microenvironmental composition and therapeutic response. By profiling rare alongside common subtypes, this atlas offers a resource for mapping pan-cancer and subtype-specific regulatory programs shaping cell-state plasticity.

Humans↗
PubMed2026

Extravascular coagulation stabilizes pro-fibrotic stromal states via tumor-intrinsic PAR1 signaling in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) exhibits a desmoplastic stroma with context-dependent tumor-restraining and tumor-promoting functions, highlighting the need to selectively reprogram stromal states. Extravascular coagulation is a prominent feature of the PDAC tumor microenvironment, yet whether it functions as an upstream regulator of fibrotic stromal states, rather than merely a byproduct of tumor-associated vascular dysfunction, has remained unclear. Here, we identify extravascular coagulation as a tumor-amplified regulatory module that stabilizes pro-fibrotic stromal states via tumor-intrinsic protease-activated receptor-1 (PAR1) signaling. To interrogate this axis mechanistically, we integrated human tumor bioinformatics with microphysiological tumor-stroma (MPTS) models that reconstruct tumor-stroma interactions under controlled coagulation exposure, followed by cross-scale validation in vivo. Analysis of The Cancer Genome Atlas (TCGA) revealed heterogeneous F2R (PAR1) expression across tumors, with elevated expression associated with fibrotic transcriptional programs and reduced survival. Consistently, thrombin induced coordinated pro-fibrotic programs in tumor cells and cancer-associated fibroblasts (CAFs), which were recapitulated in MPTS where tumor-intrinsic PAR1 was required for amplification of extracellular matrix deposition and CAF activation. Mechanistically, PAR1 signaling amplified tumor-stroma communication, in part through induction of TGF-β1-dependent pathways, establishing a reinforcing feedback loop that stabilizes fibrotic remodeling. Pharmacologic inhibition of PAR1 selectively suppressed the fibrotic transcriptional program within myofibroblastic CAFs while reducing the abundance of other CAF subtypes, reprogramming stromal states and attenuating tumor progression across MPTS and in vivo models. These findings establish a coagulation-PAR1 axis as an upstream organizer of PDAC stromal architecture and identify pharmacologic PAR1 inhibition as a mechanistically grounded strategy for selectively reprogramming the tumor-promoting stroma.

Journal Article↗
PubMed2026

miR-519d-3p inhibits gastric cancer progression by targeting the Beclin-1-dependent autophagy pathway.

Dysregulation of microRNA networks is a hallmark of gastric cancer pathogenesis, but the mechanisms driving early-stage disease remain poorly understood. This study utilized integrative bioinformatics analysis of the Gene Expression Omnibus dataset GSE158315 to identify tumor-suppressive microRNAs in early gastric cancer. We identified hsa-miR-519d-3p as a core downregulated microRNA in early-stage tissues. Functional assays in NUGC-3 and MKN-45 cell lines demonstrated that miR-519d-3p overexpression significantly suppressed cell migration and invasion, whereas its inhibition enhanced these malignant phenotypes. Dual-luciferase reporter assays confirmed that miR-519d-3p directly targets the 3' untranslated region of BECN1 (Beclin-1). Silencing Beclin-1 via siRNA mimicked the effects of miR-519d-3p overexpression, while rescue experiments showed that Beclin-1 knockdown reversed the pro-migratory and pro-invasive effects triggered by miR-519d-3p inhibition. Furthermore, monitoring of autophagic flux using mRFP-GFP-LC3 tandem reporters revealed that miR-519d-3p inhibition enhances autophagy in a Beclin-1-dependent manner. Clinical data analysis from The Cancer Genome Atlas further supported the upregulation of Beclin-1 in gastric cancer and its correlation with aggressive clinicopathological features. In conclusion, our findings establish the miR-519d-3p/Beclin-1 axis as a critical regulator of motility and autophagy in gastric cancer, representing a potential therapeutic target for early intervention.

Autophagy↗
PubMed2006

Corneal astigmatism measuring module for slit lamps.

We have developed an automatic keratometer module for slit lamps that provides automatic measurements of the radii of the corneal curvature. The system projects 72 light spots displayed in a precise circle at the examined cornea. The displacement and deformation of the reflected image of these light spots are analysed providing the keratometry. Measurements in the range of 26.8-75 D can be obtained and a self-calibration system has been specially designed in order to keep the system calibrated. Infrared LEDs indicate automatically which eye is being examined. Volunteer patients (492) have been submitted to the system and the results show that our system has a high correlation factor with the commercially available manual keratometers and the keratometry measurements from a topographer. Our developed system is 95% in agreement with the corneal topographer (Humphrey--Atlas 995 CZM) and the manual keratometer (Topcon OM-4). The system's nominal precision is 0.05 mm for the radii of curvature and 1 degree for the associated axis.

Astigmatism↗
PubMed1985

Ventricular arrhythmias. A guide to their localisation.

An electrocardiographic atlas of ventricular tachycardias was produced by pacing 27 epicardial sections of the heart and the mitral papillary muscles to simulate focal ventricular arrhythmias and simultaneously recording their 12 lead electrocardiographic appearances. One hundred and twenty nine patients undergoing cardiac surgery were studied. In five patients all 27 epicardial sites were paced at operation and in 124 individual sections were paced postoperatively with temporary epicardial wires and the electrocardiograms analysed in terms of frontal and horizontal plan QRS axis, maximum limb lead QRS amplitude, and QRS duration. Each ventricular region paced produced a distinctive 12 lead electrocardiographic pattern. Simulated right ventricular arrhythmias had either inferior frontal plane QRS axes (from the anterobasal region) or superior frontal plane QRS axes (from the apical and posterior right ventricular sections). Horizontal plane QRS axes were directed leftwards, with some posterior shift in the anteroapical regions. Simulated arrhythmias from the base of the left ventricle (anteriorly and laterally) had inferior frontal plane QRS and anterorightward horizontal plane QRS axes. Left ventricular arrhythmias with a superior frontal plane QRS axis were readily distinguished by their horizontal plane QRS axes: posterorightwards from the anterior and anterorightwards from the posterior left ventricular sections. Standard errors of the paced QRS axes for the various epicardial sections paced postoperatively ranged from 3.0 degrees to 6.0 degrees using the frontal plane axis. The electrocardiogram was most accurate in localising ventricular arrhythmias from the anterior left ventricle and least accurate for those arising from the inferior right ventricle. The appearance of the paced electrocardiograms was slightly modified by underlying disease such as myocardial infarction and left ventricular hypertrophy. This atlas may be useful in comparing the localisation of ventricular tachycardia with the site of underlying cardiac disease and may facilitate mapping in patients with refractory ventricular tachycardia requiring ablation (either surgical or by high energy impulses).

Adolescent↗
PubMed2000

Combined injuries in the upper cervical spine: clinical and epidemiological data over a 14-year period.

Concomitant traumatic injuries in the upper cervical spine are often encountered and rarely reported. We examined the data concerning 784 patients with cervical spine injuries following trauma, including 116 patients with upper cervical spine injuries. Twenty-six percent of patients with upper cervical spine injuries (31 cases) were found to have combined injuries involving either the upper or the upper and lower cervical spine. The frequent patterns were combined type I bipedicular fracture of the axis and dens fracture, and combined dens fracture and fracture of the posterior arch of C 1. Other patterns posed specific problems, such as combined dens and Jefferson fracture and combined dens and C2 articular pillar fracture. Seventy percent of atlas fractures, 30% of C2 traumatic spondylolistheses and 30% of dens fractures were part of a combination. A total of 1.7% of patients with lower cervical spine injuries had a combined injury in the upper cervical spine. A comprehensive therapeutic schedule is outlined. Combined injuries in the upper cervical spine should be sought in any patient with a cervical spine injury.

Adolescent↗
PubMed1999

Transoral fusion with internal fixation in a displaced hangman's fracture.

STUDY DESIGN: A case is reported in which late displacement of a "hangman's fracture" was managed by transoral C2-C3 fusion by using bicortical iliac crest graft and a titanium cervical locking plate. OBJECTIVES: To review the management of unstable fractures of the axis and to study other reports of transoral instrumentation of the cervical spine. SUMMARY OF BACKGROUND DATA: Undisplaced fractures of the axis are considered to be stable injuries. Although late displacement is unusual, it can lead to fracture nonunion with persisting instability and spinal cord dysfunction. In this situation, an anterior fusion of the second and third cervical vertebrae is preferred to a posterior fusion from the atlas to the third cervical vertebra, which would abolish lateral rotation between C1 and C2. METHODS: The literature on hangman's fractures was reviewed. Clinical and radiographic details of a case of C2 instability were recorded, and the particular problems posed by late displacement were considered. RESULTS: There are no other reports of transoral instrumentation of the cervical spine. A sound fusion of C2-C3 was obtained without infection or other complications. Good neck movement returned by 6 months after surgery. CONCLUSION: Undisplaced fractures of the axis are not always stable. The transoral route allows good access for stabilization of displaced hangman's fractures. In special circumstances, a locking plate may prove useful in securing the bone graft. The cervical spine locking plate can be inserted transorally with no complications and by using standard instrumentation.

Aged↗