Publications by authors named "Shin-Ichi Abe"

99 Publications

Fetal development of the carotid canal with special reference to a contribution of the sphenoid bone and pharyngotympanic tube.

Anat Cell Biol 2021 Jun;54(2):259-269

Department of Otolaryngology-Head and Neck Surgery, Tohoku University School of Medicine, Sendai, Japan.

The bony carotid canal is a tube-like bone with a rough surface in contrast to smooth surfaces of the other parts of the temporal bone petrosal portion (petrosa): it takes an impression of the additional, out-sourcing product. No study had been conducted to evaluate a contribution of the adjacent sphenoid and pharyngotympanic tube (PTT) to the carotid canal. We examined sagittal and horizontal histological sections of hemi-heads from 37 human fetuses at 10 to 37 weeks. At 10 to 18 weeks, the future carotid canal was identified as a wide loose space between the cartilaginous cochlea and the ossified or cartilaginous sphenoid elements (ala temporalis and pterygoid). A linear mesenchymal condensation extending between the cochlear wall and ala temporalis suggested the future antero-inferior margin of the carotid canal. This delineation was more clearly identified in later stages. After 25 weeks, 1) the growing pterygoid pushed the PTT upward and, in turn, the PTT pushed the internal carotid artery (ICA) upward toward the petrosa: 2) a membranous ossification occurs in the dense mesenchymal tissue, the latter of which took an appearance of an anterior process of the petrosa; 3) the bony process of the petrosa involved the ICA inside or posteriorly. The bony carotid canal was made with membranous ossification in the dense mesenchymal tissue between the petrosa and sphenoid. The mother tissue was detached from the sphenoid by the PTT. The ossification of the septum between the ICA and tympanic cavity seemed to continue after birth.
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http://dx.doi.org/10.5115/acb.20.310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225469PMC
June 2021

Histologic Investigation of the Female Vesicourethral Junction and Adjacent Tissues for Nerve-sparing Radical Cystectomy.

Urology 2021 Mar 10;149:161-167. Epub 2020 Dec 10.

Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.

Objective: To understand the structures around the vesicourethral junction and to improve functional outcomes after nerve-sparing radical cystectomy with orthotopic urinary diversion for female patients, we histologically elucidated the fibromuscular construction and nerve distribution around the vesicourethral junction.

Methods: Pelvic specimens containing all the pelvic viscera were obtained from 33 donated female cadavers. Macroslices that included the urethra, the anterior wall of the vagina, and the inferomedial edge of the levator ani muscle were made and performed elastica Masson and immunohistochemical staining. The intraoperative findings were collected in 3 female patients undergoing nerve-sparing radical cystectomy.

Results: In 18 out of the 33 cadavers, smooth muscle mass occupied a space between the urethra and the inferomedial edge of the levator ani muscle and covered the inferior margin of the bladder detrusor. We termed this mass the hiatal smooth muscle. The detrusor nerves entered the bladder, and the cavernous and sphincter nerves ran between the hiatal smooth muscle and vesicourethral junction. The boundary between hiatal smooth muscle and urethral smooth muscle was easily distinguished intraoperatively during dissection of the vesicourethral junction.

Conclusion: We found that more than half of elderly women have hiatal smooth muscle between the urethra and inferior edge of the levator ani. Autonomic nerve fibers innervating the urethral sphincter, run between the hiatal smooth muscle and vesicourethral junction in female cadavers with hiatal smooth muscle. When performing female radical cystectomy before neobladder reconstruction, nerve sparing can be reliably performed using the hiatal smooth muscle as a landmark.
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http://dx.doi.org/10.1016/j.urology.2020.12.001DOI Listing
March 2021

Mesenchymal Niche-Derived Neuregulin-1 Drives Intestinal Stem Cell Proliferation and Regeneration of Damaged Epithelium.

Cell Stem Cell 2020 10 20;27(4):646-662.e7. Epub 2020 Jul 20.

Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, VIC 3800, Australia. Electronic address:

Epidermal growth factor (EGF) maintains intestinal stem cell (ISC) proliferation and is a key component of organoid growth media yet is dispensable for intestinal homeostasis, suggesting roles for multiple EGF family ligands in ISC function. Here, we identified neuregulin 1 (NRG1) as a key EGF family ligand that drives tissue repair following injury. NRG1, but not EGF, is upregulated upon damage and is expressed in mesenchymal stromal cells, macrophages, and Paneth cells. NRG1 deletion reduces proliferation in intestinal crypts and compromises regeneration capacity. NRG1 robustly stimulates proliferation in crypts and induces budding in organoids, in part through elevated and sustained activation of mitogen-activated protein kinase (MAPK) and AKT. Consistently, NRG1 treatment induces a proliferative gene signature and promotes organoid formation from progenitor cells and enhances regeneration following injury. These data suggest mesenchymal-derived NRG1 is a potent mediator of tissue regeneration and may inform the development of therapies for enhancing intestinal repair after injury.
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http://dx.doi.org/10.1016/j.stem.2020.06.021DOI Listing
October 2020

Development and growth of the craniocervical junction with special reference to topographical relationship between the occipital basion, the anterior arch of atlas, and the odontoid process of axis: A study using human fetuses.

Anat Rec (Hoboken) 2021 02 4;304(2):353-365. Epub 2020 Jun 4.

Department of Anatomy, Tokyo Dental College, Tokyo, Japan.

The embryonic occipital bone and odontoid process of the axis are attached and connected by the notochord, but become separated in later development and growth. With special attention to the process of separation, we examined sagittal sections of the craniocervical junction in 18 human fetuses at 8-16 weeks and 22 fetuses at 31-37 weeks. At 8-9 weeks, the anterior arch of atlas was always seen overriding the occipital basal part. The odontoid process was close to the occipital with or without a transient joint cavity until 16 weeks. Near term, the top of the odontoid process was usually higher than the anterior arch, but the former was sometimes (7 of 22) at a level almost equal to or lower than the latter. The apical ligament was evident in a few specimens (5 of 22). A distance between the occipital basion and odontoid process was sometimes less than 1.5 mm (8 of 22) or less than half the thickness of the arch (10 of 22). A transient joint cavity between the basion and odontoid process was often (10 of 22). In three fetuses near term, the atlanto-occipital joint cavity was continuous with the median atlanto-axial joint cavity, and the anterior arch was overriding the occipital basal part. Therefore, rather than stage or age, individual differences were evident in the topographical relationship between the three bony elements at the craniocervical junction. An understanding of the embryology and normal development will aid in the correct interpretation of radiologic images of the pediatric cervical spine.
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http://dx.doi.org/10.1002/ar.24424DOI Listing
February 2021

A temporary disc-like structure at the median atlanto-axial joint in human fetuses.

Anat Cell Biol 2019 Dec 31;52(4):436-442. Epub 2019 Dec 31.

Department of Anatomy, Tokyo Dental College, Tokyo, Japan.

During observations of mid-term and late-stage fetuses, we found a joint disk-like structure at the anterior component of the median atlanto-axial joint. At mid-term, the disk-like structure was thick (0.1-0.15 mm) relative to the sizes of bones surrounding the joint. However, it did not completely separate the joint cavity, and was absent in the inferior and/or central part of the cavity. This morphology was similar to the so-called fibroadipose meniscoid of the lumbar zygapophysial joint that is usually seen in adults. In mid-term fetuses, there was evidence suggesting that a mesenchymal tissue plate was separated from a roof of the joint cavity. In late-stage fetuses, the thickness (less than 0.15 mm) was usually the same as, or less than that at mid-term, and the disk-like structure was often flexed, folded and fragmented. Therefore, in contrast to the zygapophysial meniscoid as a result of aging, the present disk-like structure was most likely a temporary product during the cavitation process. It seemed to be degenerated in late-stage fetuses and possibly also in newborns. Anomalies at the craniocervical junction such as Chiari malformations might accompany this disk-like structure at the median atlanto-axial joint even in childhood.
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http://dx.doi.org/10.5115/acb.19.128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952699PMC
December 2019

Morphology of the Upper Esophageal Sphincter or Cricopharyngeus Muscle Revisited: A Study Using Adult and Fetal Specimens.

Clin Anat 2020 Jul 17;33(5):782-794. Epub 2019 Nov 17.

Department of Anatomy, Tokyo Dental College, Chiyoda-ku, Tokyo, Japan.

Histological examination of specimens from 22 donated elderly cadavers and 15 human fetuses revealed that the cricopharyngeus muscle (CPM) provided (1) posterior circular muscle fibers adjacent to the external aspect of the uppermost esophageal circular muscle and (2) a thin anterior sling connecting to that same muscle. Another thick lateral bundle of longitudinal muscle originated independently from a fascia covering the posterior cricoarytenoideus muscle, extended laterally and posteriorly, and occupied a space after the CPM had disappeared at the anterolateral angle of the esophagus below the cricoid. The thick fascia contained abundant elastic fibers along the internal surface of the pharyngeal constrictors (posteromedial elastic lamina), but was interrupted or discontinued near the cricoid origin of the CPM. As no submucosal smooth muscles or elastic fibers were connected to it, the CPM did not accompany a specific elastic structure at the interface between the pharyngeal and esophageal muscles. In fetuses, the medial half of the CPM was inserted into the cricoid while the lateral half continued to the sternothyroideus muscle or ended at a fascia covering the cricothyroideus. These anterolateral ends provided a mechanical load for longitudinal growth of the pharyngeal constrictors. Consequently, the CPM was unlikely to develop and grow to form the upper esophageal sphincter, and the muscle bundle crossing the lateral aspect of the pharyngo-esophageal junction appeared to have a secondary passive role as a sphincter. This situation contrasts with that of another sphincter in the human body formed from striated muscle. Clin. Anat., 33:782-794, 2020. © 2019 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ca.23506DOI Listing
July 2020

GPR40 full agonism exerts feeding suppression and weight loss through afferent vagal nerve.

PLoS One 2019 16;14(9):e0222653. Epub 2019 Sep 16.

Cardiovascular Metabolic Drug Discovery Unit, Takeda Pharmaceutical Company Limited, Kanagawa, Japan.

GPR40/FFAR1 is a Gq protein-coupled receptor expressed in pancreatic β cells and enteroendocrine cells, and mediates insulin and incretin secretion to regulate feeding behavior. Several GPR40 full agonists have been reported to reduce food intake in rodents by regulating gut hormone secretion in addition to their potent glucose-lowering effects; however, detailed mechanisms of feeding suppression are still unknown. In the present study, we characterized T-3601386, a novel compound with potent full agonistic activity for GPR40, by using in vitro Ca2+ mobilization assay in Chinese hamster ovary (CHO) cells expressing FFAR1 and in vivo hormone secretion assay. We also evaluated feeding suppression and weight loss after the administration of T-3601386 and investigated the involvement of the vagal nerve in these effects. T-3601386, but not a partial agonist fasiglifam, increased intracellular Ca2+ levels in CHO cells with low FFAR1 expression, and single dosing of T-3601386 in diet-induced obese (DIO) rats elevated plasma incretin levels, suggesting full agonistic properties of T-3601386 against GPR40. Multiple doses of T-3601386, but not fasiglifam, in DIO rats showed dose-dependent weight loss accompanied by feeding suppression and durable glucagon-like peptide-1 elevation, all of which were completely abolished in Ffar1-/- mice. Immunohistochemical analysis in the nuclei of the solitary tract demonstrated that T-3601386 increased the number of c-Fos positive cells, which also disappeared in Ffar1-/- mice. Surgical vagotomy and drug-induced deafferentation counteracted the feeding suppression and weight loss induced by the administration of T-3601386. These results suggest that T-3601386 exerts incretin release and weight loss in a GPR40-dependent manner, and that afferent vagal nerves are important for the feeding suppression induced by GPR40 full agonism. Our novel findings raise the possibility that GPR40 full agonist can induce periphery-derived weight reduction, which may provide benefits such as less adverse effects in central nervous system compared to centrally-acting anti-obesity drugs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222653PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746387PMC
March 2020

SCO-267, a GPR40 Full Agonist, Improves Glycemic and Body Weight Control in Rat Models of Diabetes and Obesity.

J Pharmacol Exp Ther 2019 08 10;370(2):172-181. Epub 2019 Jun 10.

Takeda Pharmaceutical Company Limited, Kanagawa, Japan (H.U., R.I., H.M., H.O., Y.Mi., T.Y., Y.T., K.T., N.N.); and SCOHIA PHARMA, Inc., Kanagawa, Japan (S.A., M.O., A.K., M.W., Y.Y., T.M., Y.Mo.)

The GPR40/FFA1 receptor is a G-protein-coupled receptor expressed in the pancreatic islets and enteroendocrine cells. Here, we report the pharmacological profiles of (3)-3-cyclopropyl-3-{2-[(1-{2-[(2,2-dimethylpropyl)(6-methylpyridin-2-yl)carbamoyl]-5-methoxyphenyl}piperidin-4-yl)methoxy]pyridin-4-yl}propanoic acid (SCO-267), a novel full agonist of GPR40. Ca signaling and insulin and glucagon-like peptide-1 (GLP-1) secretion were evaluated in GPR40-expressing CHO, MIN6, and GLUTag cells. Hormone secretions and effects on fasting glucose were tested in rats. Single or repeated dosing effects were evaluated in neonatally streptozotocin-induced diabetic rats (N-STZ-1.5 rats), diet-induced obese (DIO) rats, and GPR40-knockout ( ) mice. Treatment with SCO-267 activated Gq signaling in both high- and low--expressing CHO cells, stimulated insulin secretion in MIN6 cells, and induced GLP-1 release in GLUTag cells. When administered to normal rats, SCO-267 increased insulin, glucagon, GLP-1, glucose-dependent insulinotropic peptide, and peptide YY (PYY) secretions under nonfasting conditions. These results show the full agonistic property of SCO-267 against GPR40. Hypoglycemia was not induced in SCO-267-treated rats during the fasting condition. In diabetic N-STZ-1.5 rats, SCO-267 was highly effective in improving glucose tolerance in single and 2-week dosing studies. DIO rats treated with SCO-267 for 2 weeks showed elevated plasma GLP-1 and PYY levels, reduced food intake, and decreased body weight. In wild-type mice, SCO-267 induced GLP-1 secretion, food intake inhibition, and body weight reduction; however, these effects were abolished in mice, indicating a GPR40-dependent mechanism. In conclusion, SCO-267 stimulated islet and gut hormone secretion, improved glycemic control in diabetic rats, and decreased body weight in obese rats. These data suggest the therapeutic potential of SCO-267 for the treatment of diabetes and obesity.
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http://dx.doi.org/10.1124/jpet.118.255885DOI Listing
August 2019

Suboccipital myodural bridges revisited: Application to cervicogenic headaches.

Clin Anat 2019 Oct 10;32(7):914-928. Epub 2019 Jun 10.

Department of Anatomy, Tokyo Dental College, Tokyo, Japan.

There seems to be no complete demonstration of the suboccipital fascial configuration. In 30 human fetuses near term, we found two types of candidate myodural bridge: (1) a thick connective tissue band running between the rectus capitis posterior major and minor muscles (rectus capitis posterior major [Rma], rectus capitis posterior minori [Rmi]; Type 1 bridge; 27 fetuses); and (2) a thin fascia extending from the upper margin of the Rmi (Type 2 bridge; 20 fetuses). Neither of these bridge candidates contained elastic fibers. The Type 1 bridge originated from: (1) fatty tissue located beneath the semispinalis capitis (four fetuses); (2) a fascia covering the multifidus (nine); (3) a fascia bordering between the Rma and Rmi or lining the Rma (13); (4) a fascia covering the inferior aspect of the Rmi (three); and (5) a common fascia covering the Rma and obliquus capitis inferior muscle (nine). Multiple origins usually coexisted in the 27 fetuses. In the minor Type 2 bridge, composite fibers were aligned in the same direction as striated muscle fibers. Thus, force transmission via the thin fascia seemed to be effective along a straight line. However, in the major Type 1 bridges, striated muscle fibers almost always did not insert into or originate from the covering fascia. Moreover, at and near the dural attachment, most composite fibers of Type 1 bridges were interrupted by subdural veins and dispersed around the veins. In newborns, force transmission via myodural bridges was likely to be limited or ineffective. The postnatal growth might determine a likely connection between the bridge and headache. Clin. Anat. 32:914-928, 2019. © 2019 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ca.23411DOI Listing
October 2019

Development of the pulmonary pleura with special reference to the lung surface morphology: a study using human fetuses.

Anat Cell Biol 2018 Sep 28;51(3):150-157. Epub 2018 Sep 28.

Department of Anatomy, Tokyo Dental College, Tokyo, Japan.

In and after the third trimester, the lung surface is likely to become smooth to facilitate respiratory movements. However, there are no detailed descriptions as to when and how the lung surface becomes regular. According to our observations of 33 fetuses at 9-16 weeks of gestation (crown-rump length [CRL], 39-125 mm), the lung surface, especially its lateral (costal) surface, was comparatively rough due to rapid branching and outward growing of bronchioli at the pseudoglandular phase of lung development. The pulmonary pleura was thin and, beneath the surface mesothelium, no or little mesenchymal tissue was detectable. Veins and lymphatic vessels reached the lung surface until 9 weeks and 16 weeks, respectively. In contrast, in 8 fetuses at 26-34 weeks of gestation (CRL, 210-290 mm), the lung surface was almost smooth because, instead of bronchioli, the developing alveoli faced the external surfaces of the lung. Moreover, the submesothelial tissue became thick due to large numbers of dilated veins connected to deep intersegmental veins. CD34-positive, multilayered fibrous tissue was also evident beneath the mesothelium in these stages. The submesothelial tissue was much thicker at the basal and mediastinal surfaces compared to apical and costal surfaces. Overall, rather than by a mechanical stress from the thoracic wall and diaphragm, a smooth lung surface seemed to be established largely by the thick submesothelial tissue including veins and lymphatic vessels until 26 weeks.
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http://dx.doi.org/10.5115/acb.2018.51.3.150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172594PMC
September 2018

CD57 (Leu-7, HNK-1) immunoreactivity seen in thin arteries in the human fetal lung.

Anat Cell Biol 2018 Jun 27;51(2):105-112. Epub 2018 Jun 27.

Department of Anatomy, Tokyo Dental College, Tokyo, Japan.

CD57 (synonyms: Leu-7, HNK-1) is a well-known marker of nerve elements including the conductive system of the heart, as well as natural killer cells. In lung specimens from 12 human fetuses at 10-34 weeks of gestation, we have found incidentally that segmental, subsegmental, and more peripheral arteries strongly expressed CD57. Capillaries near developing alveoli were often or sometimes positive. The CD57-positive tissue elements within intrapulmonary arteries seemed to be the endothelium, internal elastic lamina, and smooth muscle layer, which corresponded to tissue positive for a DAKO antibody reactive with smooth muscle actin we used. However, the lobar artery and pulmonary arterial trunk as well as bronchial arteries were negative. Likewise, arteries in and along any abdominal viscera, as well as the heart, thymus, and thyroid, did not express CD57. Thus, the lung-specific CD57 reactivity was not connected with either of an endodermal- or a branchial arch-origin. CD57 antigen is a sugar chain characterized by a sulfated glucuronic acid residue that is likely to exist in some glycosphingolipids. Therefore, a chemical affinity or an interaction might exist between CD57-positive arterioles and glycosphingolipids originating from alveoli, resulting in acceleration of capillary budding to make contact with the alveolar wall. CD57 might therefore be a functional marker of the developing air-blood interface that characterizes the fetal lung at the canalicular stage.
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http://dx.doi.org/10.5115/acb.2018.51.2.105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026825PMC
June 2018

Site-dependent differences in the composite fibers of male pelvic plexus branches: an immunohistochemical analysis of donated elderly cadavers.

BMC Urol 2018 May 22;18(1):47. Epub 2018 May 22.

Department of Urology, Tottori University Faculty of Medicine, Yonago, Japan.

Background: Although the pelvic autonomic plexus branches are considered to be a mixture of sympathetic and parasympathetic nerves, little is known regarding the composite fibers of the pelvic plexus branches. This study aimed to investigate the immunohistochemical features of sympathetic and parasympathetic nerves in the pelvic autonomic plexus branches.

Methods: Using 10 donated elderly male cadavers, the detailed topohistology of nerve fibers at and around the bladder, seminal vesicle, prostate, and rectum was examined. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were used as parasympathetic nerve markers; tyrosine hydroxylase (TH) was used as a sympathetic nerve marker. The myenteric plexus of the colon was utilized as a positive control.

Results: Most nerve fibers in the bladder, seminal vesicle, prostate, and rectum were both nNOS- and TH-positive. Thus, pelvic plexus branches were classified into two types: 1) triple-positive mixed nerves (nNOS+, VIP+, TH+, thick myelinated fibers + or -) and 2) double-positive mixed nerves (nNOS+, VIP-, TH+, thick myelinated fibers + or -). Notably, triple-positive nerves were localized within the posterosuperior part of the plexus (near the rectum) and travelled anteroinferiorly toward the posterolateral corner of the prostate. The posteriorly and inferiorly located nerves were predominantly composed of parasympathetic, rather than sympathetic, fibers. In contrast, nerve fibers within and along the bladder and seminal vesicle contained either no or few VIP-positive nerves. These superiorly located nerves were characterized by clear sympathetic nerve dominance.

Conclusions: The nerves of the pelvic plexus branches were clearly classified into nerves around the bladder and seminal vesicle (VIP-negative) and nerves around the prostate (VIP-positive). Although nNOS- and VIP-positive nerve fibers are candidate cavernous nerves, cavernous nerve identity cannot be definitively concluded for these nerves in the periprostatic region.
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http://dx.doi.org/10.1186/s12894-018-0369-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964883PMC
May 2018

The palatomaxillary suture revisited: A histological and immunohistochemical study using human fetuses.

Okajimas Folia Anat Jpn 2017 ;94(2):65-74

Department of Anatomy, Tokyo Dental College.

In human fetuses, the palatine process of the maxilla is attached to the inferior aspect of the horizontal plate of the palatine bone (HPPB). The fetal palatomaxillary suture is so long that it extends along the anteroposterior axis rather than along the transverse axis. The double layered bony palate disappears in childhood and the transverse suture is formed. To better understand the development of the double layered bone palate, we examined histological sections obtained from 25 fetuses of gestational age 9-11, 16-18 and 30 weeks. The double layered palate was seen in all of the specimens examined. Inferior angulation of the posterior end of the HPPB was evident at 9-11 weeks, but the initial palatine aponeurosis did not attach to the angulation but to a slightly anterior site. Both the maxilla and the HPPB were tightly attached to the vomer at 16-18 weeks. In both bones, bilateral plates met at the midline. The palatomaxillary suture was filled with short, randomly arranged collagen fibers. The nasal end of the suture was covered by a tight periosteum. Immunohistochemical examination of 3 fetuses at 16-18 weeks showed: 1) no expression of versican, tenascin-c or type II collagen in the suture; 2) few mitotic cells positive for proliferating cell nuclear antigen; 3) no or few CD34-positive developing vessels; and 4) no CD68-positive macrophages. These findings suggested that the fetal palatomaxillary suture was inactive for reconstruction and growth and that soft palate muscles likely did not contribute to the development of the double layered configuration.
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http://dx.doi.org/10.2535/ofaj.94.65DOI Listing
August 2018

Roles of CD34+ cells and ALK5 signaling in the reconstruction of seminiferous tubule-like structures in 3-D re-aggregate culture of dissociated cells from neonatal mouse testes.

PLoS One 2017 30;12(11):e0188705. Epub 2017 Nov 30.

Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.

Tissue reconstruction in vitro can provide, if successful, a refined and simple system to analyze the underlying mechanisms that drive the morphogenesis and maintain the ordered structure. We have recently succeeded in reconstruction of seminiferous cord-like and tubule-like structures using 3-D re-aggregate culture of dissociated testicular cells. In testis formation, endothelial cells that migrated from mesonephroi to embryonic gonads have been shown to be critical for development of testis cords, but how endothelial cells contribute to testis cord formation remains unknown. To decipher the roles of endothelial and peritubular cells in the reconstruction of cord-like and tubule-like structures, we investigated the behavior of CD34+ endothelial and p75+ cells, and peritubular myoid cells (PTMCs) in 3-D re-aggregate cultures of testicular cells. The results showed that these 3 types of cells had the capacity of re-aggregation on their own and with each other, and of segregation into 3 layers in a re-aggregate, which were very similar to interstitial and peritubular tissues in vivo. Observation of behaviors of fluorescent Sertoli cells and other non-fluorescent types of cells using testes from Sox9-EGFP transgenic mice showed dynamic cell movement and segregation in re-aggregate cultures. Cultures of testicular cells deprived of interstitial and peritubular cells resulted in dysmorphic structures, but re-addition of them restored tubule-like structures. Purified CD34+ cells in culture differentiated into p75+ cells and PTMCs. These results indicate that CD34+ cells differentiate into p75+ cells, which then differentiate into PTMCs. TGFβ signaling inhibitors, SB431542 and ALK5i, disturbed the reconstruction of cord-like and tubule-like structures, and the latter compromised re-construction of interstitial-like and peritubular-like structures, as well as the proliferation of CD34+, p75+, PTMCs, and Sertoli cells, and their movement and differentiation. These results indicate that CD34+ cells and signaling through ALK5 play pivotal roles in the morphogenesis of interstitial-like, peritubular-like and cord-like structures.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188705PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708723PMC
December 2017

Coccygeal body revisited: An immunohistochemical study using donated elderly cadavers.

Anat Rec (Hoboken) 2017 Oct 5;300(10):1826-1837. Epub 2017 Jun 5.

Department of Anatomy, Tokyo Dental College, Tokyo, Japan.

To describe the normal anatomy and histology of the adult coccygeal body (CB) and to discuss about the origin and function, using immunohistochemistry, we examined 29 CBs found in 32 elderly donated cadavers without macroscopic pathology in the pelvis. The CB was usually located in or near the anococcygeal ligaments. It was almost always composed of multiple masses or nodules of round glomus cells (smooth muscle actin or SMA++). However, the CB sometimes contained abundant dilated veins with scattered glomus cells. Thus, the CBs varied from the glomus cell nodule-dominant type, through an intermediate morphology with a mixture of nodules and veins, to the vein-dominant type. Each glomus cell mass was surrounded by abundant sympathetic nerves. In all specimens, we found multiple abnormal arteries, each of which carried a glomus-like cell layer around the almost -obliterated vascular lumen; as well as an SMA-negative thick arterial wall containing abundant sympathetic nerves. The ligaments around the CB are known to be under strong mechanical stress from the pelvic floor. We considered abnormal arteries containing the unique internal layer as an intermediate between a normal muscular artery and a glomus cell mass of CB. Under long-termed mechanical stress, a muscular artery seems to lose smooth muscles with increased sympathetic nerve fibers, to compensate for the lack of muscle function. Taken together with fetal morphology (our recent report), some or most of the CBs might not be an arteriovenous shunt but a result of stress-induced acquired transformation of pericytes. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1826-1837, 2017. © 2017 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ar.23615DOI Listing
October 2017

Type I neuregulin1α is a novel local mediator to suppress hepatic gluconeogenesis in mice.

Sci Rep 2017 02 20;7:42959. Epub 2017 Feb 20.

Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480, Japan.

Neuregulin1 is an epidermal growth factor (EGF)-like domain-containing protein that has multiple isoforms and functions as a local mediator in the control of various cellular functions. Here we show that type I isoform of neuregulin1 with an α-type EGF-like domain (Nrg1α) is the major isoform in mouse liver and regulates hepatic glucose production. Forced expression of Nrg1α in mouse liver enhanced systemic glucose disposal and decreased hepatic glucose production with reduced fasting blood glucose levels. Nuclear forkhead box protein O1 (FoxO1) and its downstream targets, PEPCK and G6Pase, were suppressed in liver and isolated hepatocytes by Nrg1α overexpression. In contrast, silencing of Nrg1α enhanced glucose production with increased PEPCK and G6Pase expressions in cAMP/dexamethasone-stimulated hepatocytes. Mechanistically, the recombinant α-type EGF-like domain of NRG1α (rNRG1α) stimulated the ERBB3 signalling pathway in hepatocytes, resulting in decreased nuclear FoxO1 accumulation via activation of both the AKT and ERK pathways. In addition, acute treatment with rNRG1α also suppressed elevation of blood glucose levels after both glucose and pyruvate challenge. Although a liver-specific deletion of Nrg1 gene in mice showed little effect on systemic glucose metabolism, these results suggest that NRG1α have a novel regulatory function in hepatic gluconeogenesis by regulating the ERBB3-AKT/ERK-FoxO1 cascade.
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http://dx.doi.org/10.1038/srep42959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5317163PMC
February 2017

Macrophage infiltration into thyroid follicles: an immunohistochemical study using donated elderly cadavers.

Okajimas Folia Anat Jpn 2016 ;93(3):73-80

Department of Anatomy, Tokyo Dental College.

To describe and discuss the morphology of the aged thyroid gland, with particular reference to the contribution of macrophages.With the aid of immunohistochemistry, we examined 1) macrophage accumulation, 2) infiltration of lymphocytes, and 3) the size and density of follicles in the unilateral lobe of the thyroid gland obtained from elderly donated cadavers (mean age, 84 years) without macroscopic malignancy. Each almost entire unilateral lobe of the thyroid showed 2554-9910 follicles per section, and each of the follicles ranged in area from 0.014-0.072 mm. We often found evidence suggesting absorption and fusion of follicles to provide a larger colloidal lumen, containing small follicles and/or epithelial fragments. In addition to dendritic perifollicular macrophages, large and round macrophages often formed clusters in the colloid. Colloidal lumina with weak macrophage immunoreactivity were intermingled with those showing strong reactivity. Notably, a greater number of macrophage foci in the colloid was usually associated with a lower density of perifollicular macrophages. Likewise, perifollicular macrophages were not always associated with lymphocyte infiltration. In the elderly, the initial appearance of colloidal macrophages does not appear to be associated with perifollicular infiltration of mononuclear cells. Macrophage invasion into a follicle might depend on the functional state of each follicle. After destruction of a follicle, a macrophage cluster appears to remain in the perifollicular tissue, and perhaps lymphocyte infiltration occurs secondarily. This course is likely to represent the process of degeneration of the thyroid gland structure with age.
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http://dx.doi.org/10.2535/ofaj.93.73DOI Listing
September 2017

Enteric neurons of the esophagus: an immunohistochemical study using donated elderly cadavers.

Surg Radiol Anat 2017 May 27;39(5):477-484. Epub 2017 Jan 27.

Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.

Purpose: To describe and discuss the normal anatomy and function of enteric neurons in the esophagus of aged individuals.

Method: We examined ganglion cells in esophagus specimens obtained from 15 elderly cadavers without any macroscopic pathology in the mediastinum and abdomen. Neuronal nitric oxide synthase and vasoactive intestinal polypeptide were used as parasympathetic nerve markers, and tyrosine hydroxylase as a sympathetic nerve marker.

Results: The thoracic and abdominal esophagus contained a well-developed myenteric nerve plexus (S100 protein-positive area) in the intermuscular layer: 0.02-0.03 mm per 1-mm length of the circular esophageal wall. The cervical esophagus usually contained no ganglion cells. The number of parasympathetic ganglion cells was maximal in the upper or middle thoracic esophagus (mean 18-23 cells per section), whereas sympathetic cells were considerably less numerous at any sites (mean 1-3 cells).

Conclusion: In comparison with previous data from elderly cadavers, the esophagus carried much fewer ganglion cells than the intestine and colon; sympathetic cells were particular less numerous. Esophageal smooth muscle exhibits a unique mode of peristalsis characterized by a rebound contraction with a long latency after stimulation. This type of peristalsis appears to be regulated by inhibitory, nNOS-positive nerves with a sparse distribution, which seems to account for the long-span peristalsis unique to the esophagus. The extreme sparsity of ganglion cells in the cervical esophagus suggests that enteric neuron-integrated peristalsis, like that in the intestine and colon, is unlikely. Surgical treatment of the esophagus is likely to change or impair these unique features.
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http://dx.doi.org/10.1007/s00276-016-1799-2DOI Listing
May 2017

Teres major and latissimus dorsi muscles in human embryos: A reconsideration of the so-called brother muscles.

Okajimas Folia Anat Jpn 2017 ;94(3):81-85

Department of Anatomy, Tokyo Dental College.

The teres major and latissimus dorsi muscles (TM, LD) are considered to be the so-called brother muscles. Actually, being similar to the TM, an uppermost part of the LD usually arises from the scapular plate. In embryos of 11 mm CRL, anlagen of the TM and LD appeared to be fused to provide a single mass at an angle between the axillary and radial nerves. However, splitting had already finished in not only the TM and LD but also the other muscles at and around the shoulder in specimens of 14 mm CRL. Thus, muscle splitting at the region appeared to occur simultaneously at a short stage of 12-13 mm CRL.The TM and LD carried a common tendon still at 6 weeks (14-16 mm CRL), but their muscle bellies were separated clearly. A concept of brother muscles might be applied to the TM and LD according to a bias from the gross and comparative anatomy, not from the embryological view.
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http://dx.doi.org/10.2535/ofaj.94.81DOI Listing
September 2018

Cartilage attachment morphology of the fetal cruciate ligaments of the knee: an immunohistochemical study using human fetal specimens.

Okajimas Folia Anat Jpn 2016 ;93(2):67-72

Department of Anatomy, Tokyo Dental College.

Fetal cruciate ligaments of the knee provide two types of cartilage attachments: to a cartilage fovea or a simple continuation to the perichondrium. To examine a difference in matrix substance between a ligament attachment to the fovea and another attachment to the perichondrium. We histologically observed 12 human fetal femurs in which the posterior (or anterior) cruciate ligament provided a fovea-type (or a perichondrium-type) attachment. Immunohistochemistry of matric substances (aggrecan, versican, tenascin-c) was performed. In the knees, aggrecan was consistently positive in any cartilage, versican was in the joint surface and tenascin-c in the perichondrium. In contrast to the femoral attachment, the anterior and posterior cruciate ligaments consistently continued to the perichondrium at the tibial attachment (versican-, tenascin+). In the femoral condyles, tenascin-immunoreactivity was seen in both of a fovea-type and a perichondrium-type attachments, but versican was not in both. During development of the cartilage fovea, the growing ligament seemed to push the perichondrium into the cartilage and, much or less, the tenascin-positive perichondrium was likely to be involved into the fovea.
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http://dx.doi.org/10.2535/ofaj.93.67DOI Listing
April 2017

Early embryonic development of long tendons in the human foot.

Okajimas Folia Anat Jpn 2016 ;93(2):59-65

Department of Anatomy, Tokyo Dental College.

To examine a common plantar tendinous plate for long flexors of the toe and fingers in human embryos, we observed sections of 10 embryos at 5-6 weeks (crown-rump length or CRL 15-21 mm). The heel or tuber of the calcaneus was underdeveloped in 3 embryos with CRL 15 mm and the talus appeared not to be piled up on the calcaneus but these two bones were arranged along the lateromedial axis. As reported in the hand, we demonstrated, in the deep side of tarsal bones, a common tendinous plate formed by a joining of the flexor halluces longus and flexor digitorum longus tendons. In the tendinous plate, much or less, some connections between tendons seemed to remain even after birth to provide much greater types of tendon anomalies than in the hand. In addition, we postulated a hypothetical change in course of the peroneus longus tendon. In the initial phase, because of the underdeveloped calcaneus, the peroneus tendon might take an almost straight course similar to long flexor tendons. However, at 6 weeks and later, the inferomedially expanding calcaneus beneath the talus was likely to push the tendon to the cuboid bone.
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http://dx.doi.org/10.2535/ofaj.93.59DOI Listing
April 2017

Is the ultimobranchial body a reality or myth: a study using serial sections of human embryos.

Okajimas Folia Anat Jpn 2016 ;93(2):29-40

Department of Otolaryngology and Head and Neck Surgery, Tohoku University Graduate School of Medicine.

Reported morphologies of the ultimobranchial body had varied between researchers: a cluster of mitotic cells, a duct-like structure and a rosette-like cell mass. To clarify the true morphology, we studied tilted horizontal sections of 20 human embryos (crown-rump length 5-18 mm; 4-6 weeks). The sections displayed a ladder-like arrangement of the second to fourth endodermal pouches and, in 5 early embryos we found the fifth pouch attached to the fifth ectodermal groove near the fourth pharyngeal arch artery. The bilateral fifth pharyngeal pouches protruded anterolaterally to form a U-shaped lumen surrounding the arytenoid swelling. The third to fifth pouches were each characterized by a pedal-shaped inferior end. We identified several types of cell clusters as candidates for the ultimobranchial body, but morphologically most of them were, to various degrees, likely to correspond to the blind end of the lower pouch when cut tangentially. Because of the topographical relation to the common carotid artery, a cyst-like structure with a cell cluster seemed to be the most likely candidate of the ultimobranchial body (a common anlage of the thymus and parathyroid). However, we were not able to deny a possibility that a certain plane cutting the pouch end incidentally provided such a cyst-like structure in sections. At any stage, the ultimobranchial body might not appear as a definite structure that is discriminated from others with routine staining. A concept of the ultimobranchial body might be biased by comparative anatomy that shows the ultimobranchial gland in adult birds and reptiles.
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http://dx.doi.org/10.2535/ofaj.93.29DOI Listing
April 2017

Coracobrachialis muscle and the musculocutaneous nerve: a study using human embryonic sections.

Okajimas Folia Anat Jpn 2016 ;93(1):15-20

Department of Anatomy, Tokyo Dental College.

In comparative anatomy, the musculocutaneous nerve is hypothesized to pass between the superficial and deep muscle bellies of the coracobrachialis muscle. The superficial belly is supplied by nerve branches of the lateral cord of the brachial plexus, while the deep belly by the musculocutaneous nerve. Observations of longitudinal sections of ten human embryonic arms (7 weeks; crown-rump length 26-32 mm) demonstrated that the coracobrachialis muscle was always continuous with the short head of the biceps muscle. If the aforementioned hypothesis was applied, the deep belly behind the musculocutaneous nerve course was continuous with the biceps. However, such a close relation between the coracobrachialis and biceps was not known in supplying nerves in adults. A further study using embryos of some apes without the deep belly of the coracobrachialis would be necessary for the comparison between a pattern of the embryonic muscle division and the muscle classification in comparative anatomy.
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http://dx.doi.org/10.2535/ofaj.93.15DOI Listing
April 2017

Sympathetic and parasympathetic neurons are likely to be absent in the human vestibular and geniculate ganglia: an immunohistochemical study using elderly cadaveric specimens.

Okajimas Folia Anat Jpn 2016 ;93(1):1-4

Department of Anatomy, Tokyo Dental College.

The vestibular and geniculate ganglia of the ear in experimental animals carry both of the tyrosine hydroxylase (TH)-positive sympathetic neurons and the neuronal nitric oxide synthase (nNOS)-positive parasympathetic neurons. With an aid of immunohistochemistry, we examined these ganglia as well as the horizontal part of the facial nerve using specimens from 10 formalin-fixed elderly cadavers. The submandibular ganglion from the same cadavers was used for the positive control for both markers. Although there was a nonspecific reaction in nuclei for the present antibody of nNOS, these ganglia were unlikely to contain either nNOS- or TH-positive neurons. However, we did not deny a possibility that the absence was a result of degeneration with aging. In contrast, the facial nerve horizontal part consistently contained both of TH-positive- and nNOS-positive fibers. These fibers might regulate blood supply to the facial nerve and the dysregulation leads to edema to elevate pressure on the nerve within its osseous canal.
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http://dx.doi.org/10.2535/ofaj.93.1DOI Listing
April 2017

Macrophage density in pharyngeal and laryngeal muscles greatly exceeds that in other striated muscles: an immunohistochemical study using elderly human cadavers.

Anat Cell Biol 2016 Sep 29;49(3):177-183. Epub 2016 Sep 29.

Department of Anatomy, Tokyo Dental College, Tokyo, Japan.

Macrophages play an important role in aging-related muscle atrophy (i.e., sarcopenia). We examined macrophage density in six striated muscles (cricopharyngeus muscle, posterior cricoarytenoideus muscle, genioglossus muscle, masseter muscle, infraspinatus muscle, and external anal sphincter). We examined 14 donated male cadavers and utilized CD68 immunohistochemistry to clarify macrophage density in muscles. The numbers of macrophages per striated muscle fiber in the larynx and pharynx (0.34 and 0.31) were 5-6 times greater than those in the tongue, shoulder, and anus (0.05-0.07) with high statistical significance. Thick muscle fibers over 80 µm in diameter were seen in the pharynx, larynx, and anal sphincter of two limited specimens. Conversely, in the other sites or specimens, muscle fibers were thinner than 50 µm. We did not find any multinuclear muscle cells suggestive of regeneration. At the beginning of the study, we suspected that mucosal macrophages might have invaded into the muscle layer of the larynx and pharynx, but we found no evidence of inflammation in the mucosa. Likewise, the internal anal sphincter (a smooth muscle layer near the mucosa) usually contained fewer macrophages than the external sphincter. The present result suggest that, in elderly men, thinning and death of striated muscle fibers occur more frequently in the larynx and pharynx than in other parts of the body.
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http://dx.doi.org/10.5115/acb.2016.49.3.177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052226PMC
September 2016

A RET-ER81-NRG1 Signaling Pathway Drives the Development of Pacinian Corpuscles.

J Neurosci 2016 10;36(40):10337-10355

Department of Neuroscience and

Axon-Schwann cell interactions are crucial for the development, function, and repair of the peripheral nervous system, but mechanisms underlying communication between axons and nonmyelinating Schwann cells are unclear. Here, we show that ER81 is functionally required in a subset of mouse RET mechanosensory neurons for formation of Pacinian corpuscles, which are composed of a single myelinated axon and multiple layers of nonmyelinating Schwann cells, and Ret is required for the maintenance of Er81 expression. Interestingly, Er81 mutants have normal myelination but exhibit deficient interactions between axons and corpuscle-forming nonmyelinating Schwann cells. Finally, ablating Neuregulin-1 (Nrg1) in mechanosensory neurons results in no Pacinian corpuscles, and an Nrg1 isoform not required for communication with myelinating Schwann cells is specifically decreased in Er81-null somatosensory neurons. Collectively, our results suggest that a RET-ER81-NRG1 signaling pathway promotes axon communication with nonmyelinating Schwann cells, and that neurons use distinct mechanisms to interact with different types of Schwann cells.

Significance Statement: Communication between neurons and Schwann cells is critical for development, normal function, and regeneration of the peripheral nervous system. Despite many studies about axonal communication with myelinating Schwann cells, mostly via a specific isoform of Neuregulin1, the molecular nature of axonal communication with nonmyelinating Schwann cells is poorly understood. Here, we described a RET-ER81-Neuregulin1 signaling pathway in neurons innervating Pacinian corpuscle somatosensory end organs, which is essential for communication between the innervating axon and the end organ nonmyelinating Schwann cells. We also showed that this signaling pathway uses isoforms of Neuregulin1 that are not involved in myelination, providing evidence that neurons use different isoforms of Neuregulin1 to interact with different types of Schwann cells.
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http://dx.doi.org/10.1523/JNEUROSCI.2160-16.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050328PMC
October 2016

Submucosal Elastic Laminae of the Middle and Lower Pharynx: A Histological Study Using Elderly Cadaveric Specimens.

Dysphagia 2016 10 19;31(5):635-43. Epub 2016 Jul 19.

Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.

Although the pharyngeal wall is well known to have high elasticity, the distribution of submucosal elastic fibers has not been described. Observations of histological sections of the mid and lower pharyngeal walls from 15 elderly donated cadavers were made. We found two distinct submucosal tissue layers with a high content of elastic fibers (tentatively termed the "submucosal elastic laminae"). The inferolateral elastic lamina was restricted to the level from the upper part of the arytenoid to the lower end of the inferior cornu of the thyroid cartilage. It originated from the pharyngeal submucosa, extended laterally along the inner aspect of the thyropharyngeal muscle, and inserted into the posterior margin of the thyroid cartilage including the cornu. The posteromedial lamina extended along the supero-inferior axis from a level above the greater horn of the hyoid bone to reach the muscularis mucosae of the cervical esophagus. The inferolateral and posteromedial laminae were connected at levels below the cricoarytenoid joint. Individual variations were evident in their thicknesses (ranging from almost absent to 0.3 mm) as well as the extent of connection between them. In association with striated muscle function, the inferolateral lamina seemed to suspend the lower pharyngeal mucosa, while the posteromedial lamina seemed to provide mucosal fold forcing smoothly peristaltic conveyance of a bolus during swallowing.
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http://dx.doi.org/10.1007/s00455-016-9721-yDOI Listing
October 2016

Human nasociliary nerve with special reference to its unique parasympathetic cutaneous innervation.

Anat Cell Biol 2016 Jun 24;49(2):132-7. Epub 2016 Jun 24.

Department of Anatomy, Tokyo Dental College, Chiba, Japan.

The frontal nerve is characterized by its great content of sympathetic nerve fibers in contrast to cutaneous branches of the maxillary and mandibular nerves. However, we needed to add information about composite fibers of cutaneous branches of the nasociliary nerve. Using cadaveric specimens from 20 donated cadavers (mean age, 85), we performed immunohistochemistry of tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), and vasoactive intestinal polypeptide (VIP). The nasocilliary nerve contained abundant nNOS-positive fibers in contrast to few TH- and VIP-positive fibers. The short ciliary nerves also contained nNOS-positive fibers, but TH-positive fibers were more numerous than nNOS-positive ones. Parasympathetic innervation to the sweat gland is well known, but the original nerve course seemed not to be demonstrated yet. The present study may be the first report on a skin nerve containing abundant nNOS-positive fibers. The unique parasympathetic contents in the nasocilliary nerve seemed to supply the forehead sweat glands as well as glands in the eyelid and nasal epithelium.
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http://dx.doi.org/10.5115/acb.2016.49.2.132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927428PMC
June 2016

Viable offspring obtained from Prm1-deficient sperm in mice.

Sci Rep 2016 06 2;6:27409. Epub 2016 Jun 2.

Yamamura Project Laboratory, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto 860-0811, Japan.

Protamines are expressed in the spermatid nucleus and allow denser packaging of DNA compared with histones. Disruption of the coding sequence of one allele of either protamine 1 (Prm1) or Prm2 results in failure to produce offspring, although sperm with disrupted Prm1 or Prm2 alleles are produced. Here, we produced Prm1-deficient female chimeric mice carrying Prm1-deficient oocytes. These mice successfully produced Prm1(+/-) male mice. Healthy Prm1(+/-) offspring were then produced by transferring blastocysts obtained via in vitro fertilization using zona-free oocytes and sperm from Prm1(+/-) mice. This result suggests that sperm lacking Prm1 can generate offspring despite being abnormally shaped and having destabilised DNA, decondensed chromatin and a reduction in mitochondrial membrane potential. Nevertheless, these mice showed little derangement of expression profiles.
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http://dx.doi.org/10.1038/srep27409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890041PMC
June 2016

Significant Differences in Sympathetic Nerve Fiber Density Among the Facial Skin Nerves: A Histologic Study Using Human Cadaveric Specimens.

Anat Rec (Hoboken) 2016 08 2;299(8):1054-9. Epub 2016 May 2.

Department of Anatomy, Tokyo Dental College, Chiba City, Japan.

Sympathetic nerve fibers in the skin nerves are connected with vasomotor, thermoregulatory, sensory input modulatory, and immunologic events; however, to our knowledge, no histological information is available for skin nerves in the human face. Using specimens from 17 donated cadavers (mean age, 86 years), we measured a sectional area of tyrosine hydroxylase (TH)-positive fibers in (1) the frontal nerve (V1), (2) the infraorbital nerve (V2), (3) the mental nerve (V3), (4) the greater auricular nerve (C2), (5) the auriculotemporal nerve (ATN), and (6) the zygomatic branch of the facial nerve (VII). The V1, V2, and V3 were obtained at their entrances to the subcutaneous tissue from the bony canal or notch. The V1, C2, ATN, and/or VII usually contained abundant TH-positive fibers (almost 3%-8% of the nerve sectional area), whereas the V2 and V3 consistently carried few TH-positive fibers (<1%). The difference between these two groups was quite significant (P < 0.001). Thus, from the superior cervical ganglion, the sympathetic nerve fibers reached the forehead through the frontal nerve trunk, whereas artery-bounded fibers came to the cheek, nose, and mouth. The sympathetic palsy caused by trigeminal nerve involvement is mainly characterized by the symptoms seen in the distribution of the ophthalmic division of the trigeminal nerve, such as in Horner's syndrome. It suggests that the forehead and the other facial areas are representative parts of those different sympathetic innervations that could be useful for evaluating the sympathetic function of the face in various diseases. Anat Rec, 299:1054-1059, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ar.23347DOI Listing
August 2016
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