Development of a dose distribution shifter to fit inside the collimator of a Boron Neutron Capture Therapy irradiation system to treat superficial tumours.

The Kansai BNCT Medical Center has a cyclotron based epithermal neutron source for clinical Boron Neutron Capture Therapy. The system accelerates a proton to an energy of 30 MeV which strikes a beryllium target producing fast neutrons which are moderated down to epithermal neutrons for BNCT use. While clinical studies in the past have shown BNCT to be highly effective for malignant melanoma of the skin, to apply BNCT for superficial lesions using this system it is necessary to shift the thermal neutron distribution so that the maximum dose occurs near the surface. A dose distribution shifter was designed to fit inside the collimator to further moderate the neutrons to increase the surface dose and reduce the dose to the underlying normal tissue. Pure polyethylene was selected, and a Monte Carlo simulation was performed to determine the optimum thickness of the polyethylene slab. Compared with the original neutron beam, the shifter increased the thermal neutron flux at the skin by approximately 4 times. The measured and simulated central axis depth distribution and off axis distribution of the thermal neutron flux were found to be in good agreement. Compared with a 2 cm thick water equivalent bolus, a 26% increase in the thermal neutron flux at the surface was obtained, which would reduce the treatment time by approximately 29%. The DDS is a safe, simple and an effective tool for the treatment of superficial tumours for BNCT if an initially fast neutron beam requires moderation to maximise the thermal neutron flux at the tissue surface.

Anatomy of the smooth muscle structure in the female anorectal anterior wall: convergence and anterior extension of the internal anal sphincter and longitudinal muscle.

AIM: The anatomy of the region between the vagina and anal canal plays an essential role when performing a proctectomy for low-lying tumours. However, the anatomical characteristics of this area remain unclear. The purpose of the present study was to clarify the configuration, and both lateral and inferior extensions, of the muscle bundles in the anorectal anterior wall in females. METHODS: Using cadaveric specimens, macroscopic anatomical and histological evaluations were conducted at the anatomy department of our institute. Macroscopic anatomical specimens were obtained from six female cadavers. Histological specimens were obtained from eight female cadavers. RESULTS: The smooth muscle fibres of the internal anal sphincter and longitudinal muscle extended anteriorly in the anorectal anterior wall of females and the muscle bundles showed a convergent structure. The anterior extending smooth muscle fibres merged into the vaginal smooth muscle layer, distributed subcutaneously in the vaginal vestibule and perineum and spread to cover the anterior surface of the external anal sphincter and the levator ani muscle. Relatively sparse space was observed in the region anterolateral to the rectum on histological analysis. CONCLUSION: Smooth muscle fibres of the rectum and vagina are intermingled in the median plane, and there is relatively sparse space in the region anterolateral to the rectum. Therefore, when detaching the anorectal canal from the vagina during proctectomy, an approach from both the lateral sides should be used.

An anatomical hypothesis: a "concentric-structured model" for the theoretical understanding of the surgical anatomy in the upper mediastinum required for esophagectomy with radical mediastinal lymph node dissection.

Understanding the surgical anatomy is the key to reducing surgical invasiveness especially in the upper mediastinal dissection for esophageal cancer, which is supposed to have a significant impact on curability and morbidity. However, there is no theoretical recognition regarding the surgical anatomy required for esophagectomy, although the surgical anatomy in abdominal digestive surgery has been developed on the basis of embryological findings of intestinal rotation and fusion fascia. Therefore, we developed a hypothesis of a 'concentric-structured model' of the surgical anatomy in the upper mediastinum based on human embryonic development. This model was characterized by three factors: (1) a concentric and symmetric three-layer structure, (2) bilateral vascular distribution, and (3) an 'inter-layer potential space' composed of loose connective tissue. The concentric three-layer structure consists of the 'visceral layer', the 'vascular layer', and the 'parietal layer': the visceral layer containing the esophagus, trachea, and recurrent laryngeal nerves as the central core, the vascular layer of major blood vessels surrounding the visceral core to maintain the circulation, and the parietal layer as the outer frame of the body. The bilateral vascular distribution consists of the inferior thyroid arteries and bronchial arteries originating from the bilateral dorsal aortae in an embryo. This bilateral vascular distribution may be related to the formation of the proper mesentery of the esophagus and frequent lymph node metastasis observed in the visceral layer around recurrent laryngeal nerves. The three concentric layers are bordered by loose connective tissue called the 'inter-layer potential space'. This inter-layer potential space is the fundamental factor of our concentric-structured model as the appropriate surgical plane of dissection. The peripheral blood vessels, nerves, and lymphatics transition between each layer, thereby penetrating this loose connective tissue forming the inter-layer potential space. Recurrent laryngeal nerves also transition from the vascular layer after branching off from the vagal nerves and then ascend consistently in the visceral layer. We investigated the validity of this concentric-structured model, confirming the intraoperative images and the surgical outcomes of thoracoscopic esophagectomy in a prone position (TSEP) before and after the introduction of this hypothetical anatomy model. A total of 226 patients with esophageal cancer underwent TSEP from January 2015 to December 2016. After the introduction of this model, the surgical outcomes in 105 patients clearly improved for the operation time of the thoracoscopic procedure (160 min vs. 182 min, P = 0.01) and the incidence of recurrent laryngeal nerve palsy (19.0% vs. 36.4%, P = 0.004). Moreover, we were able to identify the concentric and symmetric layer structure through surgical dissection along the inter-layer potential space between the visceral and vascular layers ('viscero-vascular space') in all 105 cases after introduction of the hypothetical model. The concentric-structured model based on embryonic development is clinically beneficial for achieving less-invasive esophagectomy by ensuring a theoretical understanding of the surgical anatomy in the upper mediastinum.

Distribution of the axillary nerve to the subacromial bursa and the area around the long head of the biceps tendon.

PURPOSE: Patients with a shoulder disorder often complain of pain on the anterior or lateral aspect of the shoulder. Such pain has been thought to originate from the suprascapular nerve. However, taking into consideration the distinctive course of the axillary nerve, the axillary nerve is likely to supply branches to the structure around the shoulder joint. This study was conducted to clarify the division, course, and distribution of the branches which originate from the axillary nerve and innervate structures around the shoulder joint. METHODS: The division, course, and distribution of the branches which originate from the axillary nerve and innervate structures around the shoulder joint were examined macroscopically by dissecting 20 shoulders of 10 adult Japanese cadavers. RESULTS: The thin branches from the anterior branch of the axillary nerve were distributed to the subacromial bursa and the area around the long head of the biceps tendon. The branches from the main trunk of the axillary nerve or the branch to the teres minor muscle were distributed to the infero-posterior part of the shoulder joint. CONCLUSION: The pain on the anterior or lateral aspect of the shoulder, which has been thought to originate from the suprascapular nerve, might be related to the thin branches which originate from the axillary nerve and innervate the subacromial bursa and the area around the long head of the biceps tendon. CLINICAL RELEVANCE: These results would be useful to consider the cause of the shoulder pain or to prevent the residual pain after the biceps tenodesis.

Disruption of the temporally regulated cloaca endodermal ß-catenin signaling causes anorectal malformations.

The cloaca is temporally formed and eventually divided by the urorectal septum (URS) during urogenital and anorectal organ development. Although congenital malformations, such as anorectal malformations (ARMs), are frequently observed during this process, the underlying pathogenic mechanisms remain unclear. ß-Catenin is a critical component of canonical Wnt signaling and is essential for the regulation of cell differentiation and morphogenesis during embryogenesis. The expression of ß-catenin is observed in endodermal epithelia, including URS epithelia. We modulated the ß-catenin gene conditionally in endodermal epithelia by utilizing tamoxifen-inducible Cre driver line (Shh(CreERT2)). Both ß-catenin loss- and gain-of-function (LOF and GOF) mutants displayed abnormal clefts in the perineal region and hypoplastic elongation of the URS. The mutants also displayed reduced cell proliferation in the URS mesenchyme. In addition, the ß-catenin GOF mutants displayed reduced apoptosis and subsequently increased apoptosis in the URS epithelium. This instability possibly resulted in reduced expression levels of differentiation markers, such as keratin 1 and filaggrin, in the perineal epithelia. The expression of bone morphogenetic protein (Bmp) genes, such as Bmp4 and Bmp7, was also ectopically induced in the epithelia of the URS in the ß-catenin GOF mutants. The expression of the Msx2 gene and phosphorylated-Smad1/5/8, possible readouts of Bmp signaling, was also increased in the mutants. Moreover, we introduced an additional mutation for a Bmp receptor gene: BmprIA. The Shh(CreERT2/+); ß-catenin(flox(ex3)/+); BmprIA(flox/-) mutants displayed partial restoration of URS elongation compared with the ß-catenin GOF mutants. These results indicate that some ARM phenotypes in the ß-catenin GOF mutants were caused by abnormal Bmp signaling. The current analysis revealed the close relation of endodermal ß-catenin signaling to the ARM phenotypes. These results are considered to shed light on the pathogenic mechanisms of human ARMs.

An anatomic study of structure and innervation of the serratus anterior muscle.

BACKGROUND: The structure and function of the serratus anterior muscle are partitioned into three parts. If the morphological characteristics in each part can be demonstrated in more detail, the cause of dysfunction will probably be identifiable more accurately. The purpose of this study was to demonstrate the details of the structure and innervation in each part of the serratus anterior muscle. MATERIALS AND METHODS: This macroscopic anatomic study was conducted using ten sides from five cadavers. The structure and innervation in each part of this muscle were examined. RESULTS: In the superior part, the independent branch was divided from a branch innervating the levator scapulae muscle. In the middle part, the long thoracic nerve descended on one-third of the anterior region between the origin and insertion. In the inferior part, the long thoracic nerve which ramified into many branches and branches from the intercostal nerves were distributed on all sides. CONCLUSION: This study demonstrated that the innervation of the serratus anterior muscle was different in each part. The difference indicates that the superior part has an intimate relation with the levator scapulae muscle while the middle and inferior parts could be the actual serratus anterior muscle. Moreover, the distribution of branches from the intercostal nerves shows that the inferior part has a connection with some trunk elements. Understanding these characteristics of innervation is useful to identify the cause of dysfunction. In addition, we assert that the constant distribution of branches from the intercostal nerves is significant for the morphology.

Low-saturation-energy-driven ultrafast all-optical switching operation in (CdS/ZnSe)/BeTe intersubband transition.

The authors report their latest results on II-VI intersubband all-optical switches in which the 10 dB absorption saturation energy is lowered to ~2.0-2.2 pJ for 1.55-1.58 mum by decreasing the thickness of the active layer and increasing the refractive index difference between the core layer and the cladding layers in waveguides. Such low saturation energies greatly improve the switching performance. <7 pJ pump energy at 1520 nm is sufficient for realizing 10 dB switching operation at 1566 nm (switching energy: ~0.7 pJ/dB). To the best of our knowledge, these switching energy and saturation energy values are the lowest reported ones for such ultrafast intersubband all-optical switches at telecommunication wavelengths.

Estimation of allele numbers at the sex-determining locus in a field population of the turnip sawfly (Athalia rosae).

Hymenopteran insects (sawflies, ants, bees, and wasps) have an unusual genetic system called haplodiploidy, where parthenogenetically produced haploid eggs become males, and fertilized, diploid eggs become females. Several hypotheses have been proposed to explain the mechanism of such sex determination, including control at a single polymorphic locus. From experiments of mother-son mating and using a genetic marker, we show that a single multiallele locus controls sex determination in the turnip sawfly (Athalia rosae). We estimated the number of alleles at this single locus in a field population by analyzing the rate of diploid males in the field and the rate of diploid males by random crossing in the laboratory. Only one diploid male was discovered in 1306 diploid larvae collected in the field. However, the number of alleles calculated by random crossing in the laboratory was 45-50. We suggest that the effective population size may be much larger than that from the areas where we collected larvae, and that there are mechanisms for avoiding inbreeding, including protogyny, dispersion, and sperm displacement by second-mated males.

Supernumerary muscle bundles in the submental triangle: their positional relationships according to innervation.

The positional relationships between the supernumerary muscle bundles within the submental triangle and their innervating branches from the mylohyoid nerve were investigated. Ten heads of Japanese cadavers that showed aberrant muscle bundles within the submental triangle were examined. Three additional heads without such aberrant bundles were used for comparison. All cadavers were fixed with 8% formalin and preserved in 30% ethanol. After the examination of the origin and insertion of the muscles, the bony elements were removed, and then their innervating branches from the mylohyoid nerve were examined in detail under a binocular microscope. In 11 head-halves of six cadavers unilateral supernumerary bundles were found. Right and left mylohyoid nerves gave off branches that crossed the inner surface of the bundles of each respective side. Supernumerary bundles ran across the median line in two heads. In one head, the twigs from the mylohyoid nerve of the same side as the mandibular origin entered the inner surface of the bundles. The other head received double innervation from right and left nerves. Three heads showed supernumerary bundles that attached to the mandible or the hyoid bone at one end and joined the mylohyoid muscle at the other end. The branches from the mylohyoid nerve of the digastric side entered the inner surface of the bundles, and those of the mylohyoid side entered their outer surface. After giving off branches to the muscles, the mylohyoid nerve continued as a cutaneous nerve of the submental region. Based on the innervation patterns of the aberrant bundles within the submental triangle, it was suggested that these bundles result from the combination of the remnants of the primordia of the mylohyoid muscle and the anterior belly of the digastric.

An anatomical study of the levator veli palatini and superior constrictor with special reference to their nerve supply.

We dissected 50 head halves of 25 Japanese cadavers (10 males, 15 females) to investigate the innervations of the levator veli palatini (LVP) and superior constrictor pharyngis. The branches supplying the LVP were classified into the following three types according to their origins: supplying branches that originated from the pharyngeal branch of the glossopharyngeal nerve (type I, four sides, 8%), branches that originated from a communicating branch between the pharyngeal branches of the glossopharyngeal and vagus nerves (type II, 36 sides, 72%), and those that originated from the pharyngeal branch of the vagus nerve (type III, 10 sides, 20%). In previous studies, supplying branches of type I were seldom described. Regarding the innervation of the superior constrictor, some variations were observed, and we consider it likely that there is a close relationship between these variations and the type of innervation of the LVP.

Spatial relationships between masticatory muscles and their innervating nerves in man with special reference to the medial pterygoid muscle and its accessory muscle bundle.

The relationships between the positional arrangement of the surrounding and innervating nerves of the muscles supplied by the mandibular nerve, in particular those medial to the main trunk of the nerve, were examined in 24 head halves from 12 Japanese cadavers by dissection from the inside after removal of the bony elements except for the mandible. In ten sides of five heads, the lingual nerve pierced the medial pterygoid muscle, and the bundle lateral to the nerve was found to be separated as an accessory muscle bundle. The accessory bundle was frequently attached to the mylohyoid muscle. In addition, the inferior alveolar nerve and the lingual nerve frequently communicated, and in four specimens a branch from the lingual nerve entered the mylohyoid to communicate with the proper nerve. The innervation pattern indicated that the medial pterygoid muscle consists of the anteromedial and the posterolateral main parts, and sometimes has an accessory bundle. Based on the present findings and the previous studies of the positional relationships between the muscles and nerves by our research group, we propose that the muscles innervated by the mandibular nerve could be classified as an inner group (the lateral pterygoid) and an outer group (the other muscles). A possible scheme of the positional relationships between the muscles and nerves is presented.

Origins and courses of the nervous branches to the male urethral sphincter.

The striated sphincter of the male urethra, the so-called rhabdosphincter, contributes significantly to urethral closure pressure. It is generally agreed that the somatic nerve fibers from the pudendal nerve innervate the rhabdosphincter, and the autonomic nerve fibers innervate the smooth muscle of the urethra. Although it is difficult to clearly identify the rhabdosphincter macroscopically, we minutely investigated the nerve branches to the urethral sphincter muscle region in 10 male pelvic halves. In addition, the origins and courses of the pudendal plexus in 88 male pelvic halves were investigated. To this region were given branches of the pudendal nerve and the pelvic plexus. The branches from the pelvic plexus to the region generally originated from S4 as the lowest branch of the pelvic splanchnic nerve, and ran along the rectal attachment of the levator ani. The caudal root of the pelvic splanchnic nerve formed a common trunk with the nerve to the levator ani (94%). Various connections were sometimes observed between the pudendal nerve and the branches medial to the levator ani. It is suggested that the somatic nerve fibers from the nerve to the levator ani or from the pudendal nerve might also join the nerve branches to the region from the pelvic plexus.

Anatomical bases for minimizing sensory disturbance after arthroscopically-assisted anterior cruciate ligament reconstruction using medial hamstring tendons.

The aim of this study was to improve surgical techniques for arthroscopically-assisted anterior cruciate ligament (ACL) reconstruction with minimal sensory disturbance in the infrapatellar and anterior lower leg regions. Thirteen patients with sensory disturbance were examined neurologically, and 51 lower limbs of 26 adult cadavers were examined anatomically to investigate the nerve branches supplying the regions. The region of sensory disturbance was supplied by branches of the medial femoral cutaneous nerve and the saphenous nerve, and the nerves showed a complementary distribution area. After detailed investigation of the positional relationships between the nerve branches and the skin incisions of the operative procedure, it was found that at least one branch of both nerves ran across the longitudinal skin incision (80%) for tendon harvest in the above-mentioned reconstruction. The complicated anatomic variations of the nerve branches preclude their absolute avoidance in any surgical incision, and a completely safe zone could not be found in the present study. However, an oblique incision for the tendon harvest rather than the typical longitudinal incision should be considered to minimize the sensory disturbance.

Nervous branch passing through an accessory canal in the sphenozygomatic suture: the temporal branch of the zygomatic nerve.

A nervous branch which passes through a small canal in the sphenozygomatic suture is sometimes observed during dissection. To examine the origin, course and distribution of this nervous branch, 42 head halves of 21 Japanese cadavers (11 males, 10 females) and 142 head halves of 71 human dry skulls were used. The branch was observed in seven sides (16.7%); it originated from the communication between the lacrimal nerve and the zygomaticotemporal branch of the zygomatic nerve or from the trunk of the zygomatic nerve. In two head halves (4.8%), the branch pierced the anterior part of the temporalis muscle during its course to the skin of the anterior part of the temple. The small canal in the suture was observed in 31 head halves (21.8%) of the dry skulls. Although this nervous branch is inconstantly observed, it should be called the temporal branch of the zygomatic nerve according to the constant positional relationship to the sphenoid and zygomatic bones. According to its origin, course and distribution, this nervous branch may be considered to be influential in zygomatic and retro-orbital pain due to entrapment and tension from the temporalis muscle and/or the narrow bony canal. The French version of this article is available in the form of electronic supplementary material and can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00276-002-0027-4.

Transforming growth factor-beta gene polymorphism in sarcoidosis and tuberculosis patients.

SETTING: Transforming growth factor-beta (TGF-beta) plays an important role in many diseases, influencing as it does such processes as immune responses, fibrosing processes, and angiogenesis. Recently, polymorphisms have been described for TGF-beta that are associated with the risk of several diseases. In this study, we investigated whether TGF-beta 1 polymorphism has an effect on sarcoidosis and tuberculosis. OBJECTIVE: TGF-beta 1 Codon 10 T869C polymorphism was investigated in 110 healthy control subjects, 104 sarcoidosis patients, and 101 tuberculosis patients. DESIGN: The TGF-beta genotype was determined using polymerase chain reaction restriction fragment length polymorphism. RESULTS: We found no significant differences in TGF-beta genotypes between sarcoidosis patients and healthy controls or tuberculosis patients and controls. The long axis of the tuberculin skin test was larger in the CC type compared with the CT type. However, there was no association between the TGF-beta genotype and the roentgenographic stage, the disappearance of shadows, or organ involvement in sarcoidosis, nor any association between genotype, the extent or type of roentgenographic shadow, or detected volume of tubercle bacilli in tuberculosis. CONCLUSION: From the results, we believe that TGF-beta polymorphisms on the whole do not have a strong influence on disease onset or clinical progression in sarcoidosis and tuberculosis, although this polymorphism might have an effect on the immune response in a tuberculosis host.

[Effects of signals on memory and comprehension of history text: insertion of signals that relate the main text with corresponding information in the margins].

History texts for elementary school children have unique discourse structures that involve variety of information and style. This study investigated the effects of signals that relate the main text with corresponding information in the margins on memory and comprehension of the text. One hundred thirty-five undergraduate students were assigned to read the text being divided into two groups: texts with signals, and texts without signals. The text with signals contained four signals, for example, "look at the picture above". After reading the text, subjects recalled the text content (written information only) and took a comprehension test. The result of recall task suggested that students who read the text with signals remembered more information in the margins than those who read the text without signals. In the comprehension test, those in the former group indicated integrated comprehension of the two parts of the text.

Phosphorylation of retinoid X receptor alpha at serine 260 impairs its metabolism and function in human hepatocellular carcinoma.

Retinoids induce apoptosis and differentiation of hepatocellular carcinoma (HCC) cells and are used clinically in the chemoprevention of HCC. We have shown previously that hepatocarcinogenesis is accompanied by accumulation of full-length retinoid X receptor alpha (RXRalpha), although the underlying mechanisms and biological implications have remained unclear. The present studies were based on the finding that the accumulated full-length RXRalpha was phosphorylated at serine/threonine residues both in all human HCC tissues examined and in human HCC-derived HuH7 cells. Phosphorylation at serine 260 of RXRalpha, a consensus site of mitogen-activated protein kinase, was closely linked to its retarded degradation, low transactivating activity, and the promotion of cancer cell growth. There was no genomic mutation in the RXRalpha gene, and abrogation of phosphorylation by mitogen-activated protein kinase-specific inhibitors restored the degradation of RXRalpha in an RXR ligand-dependent manner. These results suggest that phosphorylation of RXRalpha may interfere with its metabolism and signaling in human HCC, which could lead to growth promotion of these tumors.

Developmental expression of a unique carbohydrate antigen, Tn antigen, in mouse central nervous tissues.

Using an anti-Tn monoclonal antibody, the Tn antigen was detected immunohistochemically in prenatal and early postnatal central nervous tissues. On embryonic day 9 (E9), the antigen was distributed throughout the single neuroepithelial layer in the neocortex and then became more prominent in the preplate than in the ventricular zone along with formation of the preplate. Following division of the preplate and concomitant formation of the cortical plate, distinct labeling of the neocortex occurred in the marginal, subplate and intermediate zones, whereas in the cortical plate and ventricular zone were virtually not immunostained. It is notable that thalamocortical afferent fibers were also immunostained specifically on E14. After birth, the localization of the antigen became less noticeable and by 3 weeks after birth, the antigen had substantially disappeared. In the developing cerebellum, prominent labeling was also observed in the molecular layer and outskirts of the cerebellar nuclei on early postnatal days. To characterize the glycoprotein bearing the Tn antigen biochemically, immunoblot analysis was performed. The glycoprotein, most of which was extracted with a salt solution, migrated as a broad smeared band corresponding to a molecular weight of about 250 kDa on SDS-PAGE. Among the various tissues examined, this glycoprotein was only detected in the brain and its amount increased until an early postnatal stage with a peak on postnatal day 3 (P3), and then decreased gradually with age. This spatially and developmentally regulated expression of the Tn antigen suggests that this antigen plays a significant role in brain development.