The Membrane-Like Structure From Extensor Tendon to the Nail in the Distal End of Digits: An Anatomical Study of Structure, Function, and Utility.

METHODS: The nail structures of 6 cadavers were investigated in each of the 10 digits of the hand. In the histological study, the thickness, length, and location of the SEP were measured in each digit of 3 cadavers. In the other 3 cadavers, the moving distance of the SEP was measured macroscopically with the distal interphalangeal joint in flexion at 0 to 60 degrees for confirmation of the function. This moving distance could be considered as an indicator of the SEP straining the surrounding (retaining) structure and improving the stability of the nail in pinches. RESULT: The SEP was recognized in all the digits. The average length of the SEPs was 2.38 ± 0.11 mm (mean ± SE). The average thickness of the SEPs was 0.35 ± 0.02 mm. The nail matrix and its feeding artery were found beneath the SEP in all digits. The average moving distance of the SEP was 1.38 ± 0.06 mm. This moving distance could be considered sufficiently large to support the role of SEP in the pinches compared with the excursion of the extensor tendon at the DIP joint in a previous report. CONCLUSIONS: The SEP has been shown to play an essential role in fingertip stabilization in pinches. It can serve as an anatomical marker to avoid iatrogenic damage to the nail matrix in surgical approaches.

Morphological characterization of cholinergic partition cells: A transmitter-specific tracing study by Cre/lox-dependent viral gene expression.

BACKGROUND: Partition cells are cholinergic interneurons located in lamina VII of the spinal cord. Some partition cells are the source of the cholinergic boutons, known as C-terminals or C-boutons, that modulate the activity of spinal motor neurons. Therefore, partition cells might play an important role in motor control. Previous studies categorized partition cells into three groups (medial, intermediate, and lateral partition cells) according to their distance from the central canal. However, the morphological characteristics of the three groups remain obscure. METHODS: To analyze the morphology of partition cells, we developed an efficient technique for visualization of specific neurons at single-cell level in particular positions using adenovirus vectors and Cre/lox mediated recombination. Cre/lox conditional vectors were injected into the spinal cord of choline acetyltransferase-Cre transgenic mice, and partition cells labeled by green fluorescent protein were reconstructed from histological serial sections at the single-cell level. RESULTS: This technique allowed for the visualization of partition cells at high resolution and revealed that partition cells had various patterns of dendrite orientations and fields. Most of the visualized partition cells had more than 60% of their dendrites located in lamina VII of the spinal cord. Partition cells had dendrites extending into various Rexed's laminae (V, VI, VII, VIII, IX, and X), but none of the cells had dendrites extending dorsal to lamina IV. The dendrites of partition cells terminated both ipsilaterally and bilaterally. We also found that C-terminals on motor neurons may be derived from the middle/outer group of partition cells. CONCLUSIONS: Our results indicated that partition cells have various morphological features of the dendritic pattern and may receive differential inputs. Our results suggested that C-terminals originate not only from medial but also from intermediate/lateral cholinergic partition cells. The present study suggests that intermediate/lateral partition cells modulate activities of motor neurons through C-terminal synapses.

TrkA inhibitor promotes motor functional regeneration of recurrent laryngeal nerve by suppression of sensory nerve regeneration.

Recurrent laryngeal nerve (RLN) injury, in which hoarseness and dysphagia arise as a result of impaired vocal fold movement, is a serious complication. Misdirected regeneration is an issue for functional regeneration. In this study, we demonstrated the effect of TrkA inhibitors, which blocks the NGF-TrkA pathway that acts on the sensory/automatic nerves thus preventing misdirected regeneration among motor and sensory nerves, and thereby promoting the regeneration of motor neurons to achieve functional recovery. RLN axotomy rat models were used in this study, in which cut ends of the nerve were bridged with polyglycolic acid-collagen tube with and without TrkA inhibitor (TrkAi) infiltration. Our study revealed significant improvement in motor nerve fiber regeneration and function, in assessment of vocal fold movement, myelinated nerve regeneration, compound muscle action potential, and prevention of laryngeal muscle atrophy. Retrograde labeling demonstrated fewer labeled neurons in the vagus ganglion, which confirmed reduced misdirected regeneration among motor and sensory fibers, and a change in distribution of the labeled neurons in the nucleus ambiguus. Our study demonstrated that TrkAi have a strong potential for clinical application in the treatment of RLN injury.

Neurochemical characterization of mouse dorsal root ganglion neurons expressing organic cation transporter 2.

Organic cation transporters (OCTs) are poly-specific carriers for endogenous and exogenous cationic compounds. These are widely distributed in the nervous system and mediate neuronal activities. As antineoplastic cationic drugs accumulate in the dorsal root ganglion (DRG), OCT function has been studied mainly in cultured DRG neurons. However, the histological distribution of OCTs in the DRG is unclear. This study investigated the localization of OCT2 (a member of OCTs) in mouse DRG neurons and determined their histochemical properties. OCT2 expression was found in about 20% of DRG neurons, which were small to medium size. OCT2-expressing neurons were labeled with markers for peptidergic nociceptive (substance P or calcitonin gene-related peptide) and tactile/proprioceptive (neurofilament 200 or tropomyosin receptor kinase B or C) neurons. OCT2 was also expressed in cholinergic DRG neurons identified by choline acetyltransferase promoter-derived Cre expression. In the spinal dorsal horn, OCT2 was distributed in superficial to deep laminae. OCT2 immunoreactivity was punctate in appearance and localized in the nerve terminals of sensory afferents with labeling of neurochemical markers. Our findings suggest that OCT2 as a low-affinity, high-capacity carrier may take up substrates including cationic neurotransmitters and drugs from the extracellular space around cell bodies in DRG neurons.

Cortical Bone Trajectory for Thoracic Pedicle Screws: A Technical Note.

STUDY DESIGN: A morphometric measurement of new thoracic pedicle screw trajectory using computed tomography and a biomechanical study on cadaveric thoracic vertebrae using insertional torque. OBJECTIVE: To introduce a new thoracic pedicle screw trajectory which maximizes engagement with denser bone. SUMMARY OF BACKGROUND DATA: Cortical bone trajectory (CBT) which maximizes the thread contact with cortical bone provides enhanced screw purchase. Despite the increased use of CBT screws in the lumbar spine, no study has yet reported the insertional technique for thoracic CBT. METHODS: First, the computed tomography scans of 50 adults were studied for morphometric measurement of lower thoracic CBT. The starting point was determined to be the intersection of the lateral two thirds of the superior articular process and the inferior border of the transverse process. The trajectory was straight forward in the axial plane angulated cranially targeting the posterior third of the superior endplate. The maximum diameter, length, and the cephalad angle were investigated. Next, the insertional torque of pedicle screws using this new technique was measured and compared with that of the traditional technique on 24 cadaveric thoracic vertebrae. RESULTS: All morphometric parameters of thoracic CBT increased from T9 to T12 (the mean diameter: from 5.8 mm at T9 to 8.5 mm at T12; the length: from 29.7 mm at T9 to 32.0 mm at T12; and the cephalad angle: from 21.4 degrees at T9 to 27.6 degrees at T12). The mean maximum insertional torque of CBT screws and traditional screws were 1.02±0.25 and 0.66±0.15 Nm, respectively. The new technique demonstrated average 53.8% higher torque than the traditional technique (P<0.01). CONCLUSIONS: The detailed morphometric measurement and favorable screw fixation stability of thoracic CBT are reported. The insertional torque using thoracic CBT technique was 53.8% higher than that of the traditional technique.

Value of a novel PGA-collagen tube on recurrent laryngeal nerve regeneration in a rat model.

OBJECTIVES/HYPOTHESIS: Nerbridge (Toyobo Co., Ltd., Osaka, Japan) is a novel polyglycolic acid (PGA) tube that is filled with collagen fibers and that facilitates nerve fiber expansion and blood vessel growth. It is biocompatible and commercially available, with governmental approval for practical use in Japan. We hypothesized that the PGA-collagen tube would promote regeneration of the recurrent laryngeal nerve (RLN). This hypothesis was examined in a rat axotomy model of the RLN. STUDY DESIGN: Prospective animal study. METHODS: The axotomy model was established by transection of the left RLN in adult Sprague-Dawley rats. The cut ends of the nerve were bridged using Nerbridge (Toyobo Co., Ltd.) with a 1-mm gap (tube-treatment group) or direct sutures (sutured-control group). Left vocal fold mobility, nerve conduction velocity, morphology, and histology were assessed after 15 weeks. RESULTS: Fifteen weeks after treatment, nerve fiber connections were observed macroscopically in both groups, and more clear myelinated fibers and better prevention of laryngeal muscle atrophy were observed in the tube-treatment group compared with the sutured-control group. However, vocal fold movement recovery was not observed in either group, and the conduction velocity of the RLN did not differ between the two groups. CONCLUSIONS: Better nerve regeneration was observed in the tube-treatment group. The combination therapy with molecular or gene therapy might be an effective strategy to improve vocal fold movement. The PGA-collagen tube has the potential to promote regeneration of the RLN and to be a scaffold for drug administration in these combination therapies. LEVEL OF EVIDENCE: N/A. Laryngoscope, 126:E233-E239, 2016.

Redundant roles of Sox17 and Sox18 in postnatal angiogenesis in mice.

Sox7, Sox17 and Sox18 constitute group F of the Sox family of HMG box transcription factor genes. Dominant-negative mutations in Sox18 underlie the cardiovascular defects observed in ragged mutant mice. By contrast, Sox18(-/-) mice are viable and fertile, and display no appreciable anomaly in their vasculature, suggesting functional compensation by the two other SoxF genes. Here, we provide direct evidence for redundant function of Sox17 and Sox18 in postnatal neovascularization by generating Sox17(+/-) -Sox18(-/-) double mutant mice. Whereas Sox18(-/-) and Sox17(+/-) -Sox18(+/-) mice showed no vascular defects, approximately half of the Sox17(+/-) -Sox18(-/-) pups died before postnatal day 21 (P21). They showed reduced neovascularization in the liver sinusoids and kidney outer medulla vasa recta at P7, which most likely caused the ischemic necrosis observed by P14 in hepatocytes and renal tubular epithelia. Those that survived to adulthood showed similar, but milder, vascular anomalies in both liver and kidney, and females were infertile with varying degrees of vascular abnormalities in the reproductive organs. These anomalies corresponded with sites of expression of Sox7 and Sox17 in the developing postnatal vasculature. In vitro angiogenesis assays, using primary endothelial cells isolated from the P7 livers, showed that the Sox17(+/-) -Sox18(-/-) endothelial cells were defective in endothelial sprouting and remodeling of the vasculature in a phenotype-dependent manner. Therefore, our findings indicate that Sox17 and Sox18, and possibly all three SoxF genes, are cooperatively involved in mammalian vascular development.

A close correlation in the expression patterns of Af-6 and Usp9x in Sertoli and granulosa cells of mouse testis and ovary.

Usp9x, an X-linked deubiquitylating enzyme, is stage dependently expressed in the supporting cells (i.e. Sertoli cells and granulosa cells) and germ cells during mouse gametogenesis. Af-6, a cell junction protein, has been identified as a substrate of Usp9x, suggesting a possible association between Usp9x and Af-6 in spermatogenesis and oogenesis. In this study, we examined the expression pattern of Af-6 and Usp9x and their intracellular localization in testes and ovaries of mice treated with or without pregnant mare serum gonadotropin (PMSG), an FSH-like hormone. In both testes and ovaries, Af-6 expression was predominantly observed in supporting cells, as well as in steroidogenic cells, but not in any germ cells. In Sertoli cells, Af-6 was continuously expressed throughout postnatal and adult stages, where both Af-6 and Usp9x were enriched at the sites of Sertoli-Sertoli and Sertoli-spermatid junctions especially at stages XI-VI. In the granulosa cells, Af-6, as well as Usp9x, was highly expressed in primordial and primary follicles, but its expression rapidly decreased after the late-secondary follicle stage. Interestingly, in PMSG-treated mice, the expression levels of Af-6 and Usp9x were synchronously enhanced, slightly in Sertoli cells and strongly in granulosa cells of the late-secondary and Graafian follicles. Such closely correlated expression patterns between Af-6 and Usp9x clearly suggest that Af-6 may be deubiquitylated by Usp9x in both Sertoli and granulosa cells. It further suggests that the post-translational regulation of Af-6 by Usp9x may be one potential pathway to control the cell adhesion dynamics in mammalian gametogenesis.

Lectin histochemical study on the olfactory organ of the newt, Cynops pyrrhogaster, revealed heterogeneous mucous environments in a single nasal cavity.

Expression patterns of glycoconjugates were examined by lectin histochemistry in the nasal cavity of the Japanese red-bellied newt, Cynops pyrrhogaster. Its nasal cavity consisted of two components, a flattened chamber, which was the main nasal chamber (MNC), and a lateral diverticulum called the lateral nasal sinus (LNS), which communicated medially with the MNC. The MNC was lined with the olfactory epithelium (OE), while the diverticulum constituting the LNS was lined with the vomeronasal epithelium (VNE). Nasal glands were observed beneath the OE but not beneath the VNE. In addition, a secretory epithelium was revealed on the dorsal boundary between the MNC and the LNS, which we refer to as the boundary secretory epithelium (BSE) in this study. The BSE seemed to play an important role in the construction of the mucous composition of the VNE. Among 21 lectins used in this study, DBA, SBA and Jacalin showed different staining patterns between the OE and the VNE. DBA staining showed remarkable differences between the OE and the VNE; there was intense staining in the free border and the supporting cells of the VNE, whereas there was no staining or weak staining in the cells of the OE. SBA and Jacalin showed different stainings in the receptor neurons for the OE and the VNE. Furthermore, UEA-I and Con A showed different stainings for the nasal glands. UEA-I showed intense staining in the BSE and in the nasal glands located in the ventral wall of the MNC (VNG), whereas Con A showed intense staining in the BSE and in the nasal glands located in the dorsal and medial wall of the MNC (DMNG). The DMNG were observed to send their excretory ducts into the OE, whereas no excretory ducts were observed from the VNG to the OE or the VNE. These results suggested that the secretion by the supporting cells as well as the BSE and the DMNG establishes that there are heterogeneous mucous environments in the OE and the VNE, although both epithelia are situated in the same nasal cavity.