Maternal malnourishment induced upregulation of fetuin-B blunts nephrogenesis in the low birth weight neonate.

Maternal undernutrition during pregnancy (MUN) often leads to low birth weight (LBW) neonates that have a reduced total nephron endowment, leaving these neonates susceptible to kidney disease throughout their lives. For reasons unknown, these LBW neonates have impaired kidney development due to a severe reduction in renal SIX2+ stem cells during nephrogenesis. Using a mouse model of MUN, we investigated SIX2+ stem cell reduction in the LBW neonate. Significant upregulation of the protein fetuin-B (measured by PCR and immunoblotting) in the MUN mother's placenta, organs and circulation yielded a 3-fold increase of this protein in the embryonic kidney. Recombinant fetuin-B, administered to healthy pregnant mothers at the concentration equivalent to that in the MUN mother, crossed the placenta and reduced both SIX2+ stem cells by 50% and nephron formation by 66% in embryonic kidneys (measured by immunofluorescence and the physical dissector/fractionator stereological method). Administration of fetuin-B to kidney explants yielded similar reductions in renal SIX2+ stem cells and nephron formation. Fetuin-B treatment of isolated embryonic renal SIX2+ stem cell primary cultures 1) increased NF-kB activity and apoptosis, 2) reduced cell proliferation due to upregulated p21 nuclear activity and subsequent cell cycle arrest, and 3) enhanced generation of reactive oxygen species (measured by fluorescence microscopy). In conclusion, MUN increases fetuin-B in the developing embryonic kidney. The increase in fetuin-B blunts nephrogenesis by reducing SIX2+ stem cells by promoting their apoptosis (via NF-kB upregulation), blunting their proliferative renewal (via p21 upregulation) and enhancing oxidative stress.

Surgical relevance of the lateral costotransverse ligament in relation to the dorsal root ganglion.

The lateral costotransverse ligament, a short band that stabilizes the costovertebral joint, is found in close proximity to the dorsal root ganglion. This ligament is an important surgical landmark during tumor resections or nerve blocks in the paravertebral space. The purpose of this study was to quantitatively and qualitatively describe the morphology of the lateral costotransverse ligament and its relation to the dorsal root ganglion at all levels of the thoracic spine. The thoracic spines of eight embalmed cadavers were dissected bilaterally. The length, width, and thickness of the ligament were measured. The distance from the inferolateral aspect of the ligament to the lateral aspect of the dorsal root ganglion was also measured. Three bilateral groups of lateral costotransverse ligaments, top (on ribs 1-2), middle (on ribs 3-10), and bottom (on ribs 11-12), were compared based on anatomic distinctions between the costotransverse joints, which can influence ligament morphology. Among the three groups, the differences between the length, width, and thickness were not statistically significant. However, the distance from the lateral costotransverse ligament to the dorsal root ganglion differed significantly (P = 0.000), with the middle group having the longest distance, and the bottom group having the shortest distance. This finding can help clinicians and surgeons avoid iatrogenic injuries of neural structures during thoracic spine surgery, or when performing nerve blocks in the paravertebral space.

Morphometric analysis of temporomandibular joint elements.

PURPOSE: To study the morphology of temporomandibular joint (TMJ) elements and examine the feasibility of a novel biofidelic articular disc casting technique. METHODS: 18 formalin-fixed cadavers (77.8% female, 22.2% male) with mean (SD) death age of 71.9 (13.7) years were used for this study. In each specimen the masseter muscle, mandibular ramus, and articular disc were dissected bilaterally and measured for length, width, and thickness. All anatomic measurements were made using a digital slide caliper (Hawk Inc., Cleveland, OH). Further, a novel method for the creation of biofidelic articular disc models was established through trial and error. Models were measured for accuracy against their biological counterparts. RESULTS: Left articular disc length and thickness were inversely correlated (r = -0.58, p < 0.049). Direct correlations existed between right disc and ramus thickness (r = 0.56, p < 0.039), masseter length and thickness (r = 0.59, p < 0.009), and masseter width and thickness (r = 0.66, p < 0.003). Comparison of the model measurements with their biological counterparts found no significant differences. DISCUSSION: These observed correlations between elements of the TMJ hold relevance for oral-maxillofacial surgeons and researchers examining disorders of the TMJ. Additionally, our casting technique proved accurate in modeling human articular discs.

Anatomical Study of the Cervical and Interosseous Talocalcaneal Ligaments of the Foot with Surgical Relevance.

There is conflicting evidence regarding the morphology and orientation of the cervical ligament (CL) and interosseous talocalcaneal ligament (ITCL). The morphology of the CL and its relationship to the ITCL were studied to obtain an understanding of these structures. Twenty-six feet (13 left, 13 right) were obtained from formalin-fixed cadavers (14 females, four males) with the mean standard deviation (SD) age at death 80.9 (12.9) years. All measurements were made with a digital caliper. The length and width of the foot, the width and height of the talus, were measured. The talus was cut coronally to expose the ITCL and qualitative observations were noted. The mean (SD) heights and widths of the CL at the anterior, posterior, superior, and inferior points were 8.27 (2.52), 13.95 (5.96), 9.15 (2.45), and 11.90 (4.30) mm, respectively. The mean (SD) thicknesses of the CL at the superoanterior, superoposterior, inferoanterior, inferoposterior, and central points were 0.62 (0.24), 1.05 (0.30), 0.70 (0.26), 1.20 (0.34), and 0.97 (0.31) mm, respectively. The fibers of the CL are oriented at a slight superoanterior to inferoposterior angle, whereas the fibers of the ITCL are oriented in a slight superomedial to inferolateral angle. The fibers of the CL and ITCL overlap inside the tarsal sinus with the CL positioned anteriorly, which helps to distinguish the two ligaments. In this study, we identified the morphometrics of the CL and described the CL and ITCL qualitatively. These results are relevant to introducing innovative techniques for reconstructive surgery of the subtalar ligaments in order to repair, for example, subtalar instability.

Relationship Between the Intersesamoid Ligament and Sesamoid Bones in Cadaveric Feet with Hallux Valgus.

There is heterogeneity in the literature regarding the anatomy, exact location, and definition of the intersesamoid ligament (IL). Anatomic knowledge of the IL and its variations are important for surgeons who undertake corrective surgery for hallux abducto valgus (HAV). The IL was dissected in 16 feet from 32 formalin-fixed cadavers (12 females, four males; mean age at death, 76.6 years) to examine its morphology. The length, width, and thickness of its constituent bands were recorded with a digital caliper. Descriptive and correlational statistics were used to investigate the relationships between band size, age at death, and sex. A literature review was conducted to compare our data to those of previous studies. Results suggest that the size of the sesamoids may change as a result of HAV deforming forces, which may cause lengthening of the IL. The IL stabilizes the sesamoid apparatus of the first metatarsophalangeal joint (MPJ) and should be evaluated in HAV correction. Anatomic knowledge of the complex morphology and relations between the IL and sesamoids is critically important for surgeons correcting HAV deformities.

The avascular zone and neuronal remodeling of the fovea in Parkinson disease.

Inner foveal thinning and intracellular alpha-synuclein were demonstrated in the retina in Parkinson disease. While pathognomonic alpha-synuclein is associated with embryonic dopaminergic (DA) neurons, postmortem studies in the nervous system and retina show prominent effect also in non-DA neurons. We evaluated foveal capillaries and foveal thickness in 23 Parkinson disease subjects and 13 healthy controls using retinal fluorescein angiography and optical coherence tomography. The size of the foveal avascular zone inversely correlates with foveal thinning. Foveal thinning highly correlates with motor impairment and also disease duration. Quantifying capillary and neuronal remodeling could serve as biological markers.

Anatomic study of the deltoid ligament of the ankle.

BACKGROUND: There is heterogeneity in the literature regarding the anatomy and number of ligamentous bands that form the deltoid ligament (DL). Anatomic knowledge of the DL and its variations are important for surgeons who repair ankle fractures. METHODS: The DL was dissected in 33 ankles from 17 formalin-fixed cadavers (mean age at death, 76.6 years) to examine its morphology. The length, width, and thickness of its constituent bands were recorded with a digital caliper. Descriptive and correlational statistics were used to investigate the relationships between band size, age at death, and sex. A literature review was conducted to compare our data to those of previous studies. RESULTS: The DL has superficial and deep layers with up to 8 different bands. CONCLUSION: The DL stabilizes the medial ankle and should be evaluated in flatfoot deformities and severe ankle fractures. CLINICAL RELEVANCE: Anatomic knowledge of DL variations should aid the surgeon in repairing torn DLs.

Morphometry of the fibular collateral ligament: anatomic study with comprehensive review of the literature.

There is no consensus in the literature related to the morphology, bony attachments, and variations of the fibular collateral ligament (FCL) of the knee. Our purpose was to investigate FCL morphology and to review reports in the literature regarding this structure. Seventy knees from formalin-fixed, adult cadavers were dissected and a digital caliper was used to measure FCL length, width, distance from proximal attachment to articular surface (PA→AS), and distance from distal attachment to articular surface (DA→AS). The mean (SE) length and width of all FCLs was 48.3 (1.1) mm and 4 (0.16) mm, respectively. The mean (SE) PA→AS and DA→AS of all FCLs was 22 (0.8) mm and 24.8 (1) mm, respectively. We found a direct relationship between the PA→AS and DA→AS distances (Spearman rho = 0.527, P = 0.002) and this association was independent of age and sex. Two FCL variations were found: a bifurcate ligament with two distal bands and a trifurcate ligament with three distal bands, all of which attached to the fibular head. Our literature review revealed that only 2/10 cadaveric FCL morphology studies reported variations similar to the current study. Further, there was variability in the reported location of the FCL proximal attachment. When combining our data with these studies, 105/219 FCLs directly attached to the apex of the lateral epicondyle (LE), 10/219 to a fovea posterior to the LE, and 104/219 posterior and proximal to the LE. These data may have implications related to FCL injury and repair.

α-synuclein in the inner retina in parkinson disease.

Behavioral, electrophysiological, and imaging data reveal impaired visual processing and altered retinal morphology in Parkinson disease. Are visual changes epiphenomena? We report the presence of misfolded α-synuclein in the retina, not hitherto shown, in discrete retinal neurons within the inner retina. They demonstrate the histopathology that may underlie impaired vision and retinal remodeling in Parkinson disease. Furthermore, the histological localization of α-synuclein gives clues to the nonsynaptic mode of α-synuclein propagation.

A chemical application method with underwater dissection to improve anatomic identification of cadaveric foot and ankle structures in podiatric education.

BACKGROUND: Many cadaver-based anatomy courses and surgical workshops use prosections to help podiatry students and residents learn clinically relevant anatomy. The quality of these prosections is variable and dependent upon the methods used to prepare them. These methods have not been adequately described in the literature, and few studies describe the use of chemicals to prepare prosections of the cadaveric foot and ankle. Recognizing the need for better teaching prosections in podiatric education, we developed a chemical application method with underwater dissection to better preserve anatomic structures of the cadaveric foot and ankle. METHODS: We used inexpensive chemicals before, during, and after each step, which ultimately resulted in high-quality prosections that improved identification of anatomic structures relevant to the practice of podiatric medicine. RESULTS: Careful preservation of clinically important nerves, vessels, muscles, ligaments, and joints was achieved with these prosections. CONCLUSIONS: Although this method required additional preparation time, the resultant prosections have been repeatedly used for several years to facilitate learning among podiatry students and residents, and they have held up well. This method can be used by educators to teach podiatry students throughout their medical training and even into residency.

The transverse occipital ligament: an anatomic, histologic, and radiographic study.

BACKGROUND CONTEXT: The craniocervical region is an osteoligamentous complex that provides structural stability and movement by means of numerous ligaments. Fundamental knowledge of these ligaments is important for physicians who treat patients with disorders of this region to reduce morbidity and mortality. There is a paucity of data in the literature regarding the morphology, function, and classification of the transverse occipital ligament (TOL). PURPOSE: The purpose of this study was to investigate the prevalence, morphology, and variations of the TOL in a large number of adult human cadavers using dissection, histology, and digital radiography. STUDY DESIGN: Cadaveric laboratory study. SAMPLE: Thirty-two formalin-fixed human adult cadavers were dissected in the study. Fourteen cadavers were found to have a TOL. OUTCOME MEASURES: Measurements using a digital caliper, high-resolution digital photography, histologic staining with bright-field microscopy, and digital radiography. METHODS: The posterior musculature and related soft tissues were dissected and underlying bony elements removed. The TOL was identified, isolated, measured, and then removed for histologic preparation with hematoxylin and eosin staining. Anteroposterior open-mouth digital radiographs of the upper cervical spine with monofilament attached to the TOL were used to demonstrate its relations to the occiput, atlas, and axis. RESULTS: The TOL was present in 14 of 32 (44%) of the dissected cadavers (six male and eight female). Three types of TOLs were identified. Type 1 had bilateral connections to the alar ligaments and had fibers inserting onto the dens. Type 2 also had bilateral connections to the alar ligaments but did not have fibers inserting onto the dens. Type 3 neither had any connections to the alar ligaments nor had fibers that connected to the dens. Male cadavers always had a Type 1 TOL compared with 3 of 8 (38%) female cadavers and this difference was significant (p=.031). The TOL consisted of dense regular connective tissue with parallel arrangements of collagen fibers and interposed fibroblasts. CONCLUSIONS: Our data suggest that the TOL is not an anatomic variant and can be classified into three types. Future biomechanical studies can be designed to investigate the function of the TOL, although we hypothesize that it may act as a fulcrum during flexion and extension of the head because it is located between the apical ligament and superior crus of the cruciform ligament. Anteroposterior open-mouth digital radiographs revealed the location of the TOL with respect to the upper two cervical vertebrae. Future research should investigate the radiologic characteristics of the TOL using magnetic resonance imaging.

Phospholipase D1 is associated with amyloid precursor protein in Alzheimer's disease.

Amyloid precursor protein (APP) is a widely expressed transmembrane protein of unknown function that is involved in the pathogenesis of Alzheimer's disease (AD). We investigated the involvement of phospholipase D (PLD) in the pathophysiology of AD. We showed dramatic upregulation of PLD1 immunoreactivity in reactive astroglial cells in brain tissue sections from authentic AD patients. Expression and activity of PLD1 were up-regulated in brain tissues from AD patients, especially caveolae membrane fraction, compared with those of control brains. Interestingly, PLD1 physically interacts and colocalizes with APP and caveolin-3. We found that APP was associated with the pleckstrin homology domain of PLD1, and the amyloid region of APP interacted with PLD. Elevated expression of APP stimulated PLD activity in human astroglioma cells. These results suggest that up-regulation of PLD might have a role in the neuronal pathology associated with AD.

Phospholipase D1 is up-regulated in the mitochondrial fraction from the brains of Alzheimer's disease patients.

Mitochondrial dysfunction may play an important role in sporadic Alzheimer's disease (AD) progression. Recently, we have reported that amyloid precursor protein (APP) stimulates phospholipase D (PLD) activity and beta-amyloid (Abeta) region of APP is involved in the interaction with PLD1. To elucidate the involvement of PLD in the pathophysiology of AD, we examined the expression of PLD1 and alteration of membrane phospholipid in mitochondrial membranes of control and AD brains using Western blot and phospholipid analysis by thin layer chromatography (TLC). We have found that protein expression of PLD1 was significantly increased in mitochondrial fraction of brains of AD patients compared with that in control brains. Furthermore, the concentration of mitochondrial phospholipids such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was increased and the content of phosphatidic acid (PA), a product of PLD activity, was up-regulated in the mitochondrial membrane fractions of AD brain compared with that of control brain. These results suggest that up-regulation of PLD1 in the mitochondrial fraction of AD brain might affect the composition of membrane phospholipids and provide a clue to the mechanism underlying the mitochondrial dysfunction associated with AD.

Expression of calsenilin in neurons and astrocytes in the Alzheimer's disease brain.

Calsenilin, a multifunctional Ca2+-binding protein, has been identified as an Alzheimer's disease-associated presenilin interactor. Here, we investigated the histochemical localization of calsenilin and its expression levels in the brains of sporadic Alzheimer's disease. Both messenger RNA and protein expression of calsenilin were observed in neurons of the cerebral cortex and hippocampus of control brains, and more intense staining was in Alzheimer's disease brains. Although calsenilin is primarily expressed in neurons, its immunoreactivity was also detected in reactive astrocytes of the Alzheimer's disease brains. In Alzheimer's disease brains, the caspase-derived fragment of calsenilin was only detected in cytosolic fraction. Our findings suggest that calsenilin overexpression in both neurons and reactive astrocytes may play an important role in apoptosis and in Alzheimer's disease pathology.