Sixth cranial nerve palsy and trigeminal neuropathic pain due to a space-occupying lesion.

Various neuropathies of the cranil nerves can accompany trigeminal neuropathic pain attributed to space-occupying lesions. In this case report, the patient presented with persistent intraoral pain and numbness on the right side of the face. Cranial nerve examination revealed dysfunctional eye movements, diplopia, and mechanical hyposensitivity in the mandibular region. The patient was diagnosed with neuropathy due to intracranial lesions and referred to the Department of Neurosurgery and Otorhinolaryngology. The patient was suspected of having malignant lymphoma and is currently undergoing neurosurgical intervention. This article discusses the importance of the examination of the cranial nerve for patients with persistent pain in the trigeminal nerve distribution.

Post-Traumatic Trigeminal Neuropathic Pain after Dental Implant Surgery and the Injustice Experience Questionnaire.

Painful post-traumatic trigeminal neuropathy (PTTN) is a known complication of dental implant therapy. Patients with PTTN develop sensory abnormalities in the orofacial region, which may be a psychosocial aspect, and dentists should assess somatosensory testing and psychosocial factors. The patients were assessed using quantitative sensory testing (QST). A 64-year-old female presented with allodynia of the left lower lip that occurred after a surgical implant procedure. Persistent pain started 4 months after the placement of two dental implants in the mandible. Sensory testing of these areas revealed warm hyposensitivity and mechanical hypersensitivity of the mandibular region. We also assessed PTTN-related perceived injustice using the Injustice Experience Questionnaire. The patient refused medication therapy such as pregabalin; therefore, autogenic training was adopted as an alternative management strategy. We conclude that for expensive dental procedures, such as implant placement, sufficient consensus should be obtained preoperatively before proceeding with surgery.

Potential roles of the IL-6 family in conjunctival fibrosis.

Elevated intraocular pressure (IOP) is a significant risk factor for vision loss due to glaucoma, which is a major cause of blindness worldwide. Glaucoma filtration surgery (GFS) is an important method to reduce IOP by guidance of aqueous humor into a newly built filtration bleb in the conjunctiva; management of the wound healing mechanism is essential for the success of GFS. Here, we investigated the roles of interleukin (IL)-6 family members during the wound healing process after GFS. At the surgical site, the expression levels of genes encoding IL-6, oncostatin M (OSM), their receptors, and collagen I were elevated at 3 h after GFS, whereas the levels of genes encoding transforming growth factor (TGF)-ß, α-smooth muscle actin (SMA), type IV collagen, and fibronectin were elevated at 3 days after GFS. IL-6 trans-signaling and OSM signaling suppressed TGF-ß-induced expression of α-SMA and collagen IV, as well as activation of the non-canonical TGF-ß pathway, suggesting that IL-6 and OSM may aid in controlling the phase transition from inflammation to proliferation and remodeling. The suppressive effects of OSM were accompanied by STAT3 activation, such that STAT1 function was complementary to STAT3. Taken together, these observations indicated that IL-6 family members constitute early response genes after GFS, which can suppress TGF-ß-induced expression of late response genes at the surgical site after GFS.

N6-methyladenosine (m6A) is an endogenous A3 adenosine receptor ligand.

About 150 post-transcriptional RNA modifications have been identified in all kingdoms of life. During RNA catabolism, most modified nucleosides are resistant to degradation and are released into the extracellular space. In this study, we explored the physiological role of these extracellular modified nucleosides and found that N6-methyladenosine (m6A), widely recognized as an epigenetic mark in RNA, acts as a ligand for the human adenosine A3 receptor, for which it has greater affinity than unmodified adenosine. We used structural modeling to define the amino acids required for specific binding of m6A to the human A3 receptor. We also demonstrated that m6A was dynamically released in response to cytotoxic stimuli and facilitated type I allergy in vivo. Our findings implicate m6A as a signaling molecule capable of activating G protein-coupled receptors (GPCRs) and triggering pathophysiological responses, a previously unreported property of RNA modifications.

Microglia-Astrocyte Communication via C1q Contributes to Orofacial Neuropathic Pain Associated with Infraorbital Nerve Injury.

Trigeminal nerve injury causes a distinct time window of glial activation in the trigeminal spinal subnucleus caudalis (Vc), which are involved in the initiation and maintenance phases of orofacial neuropathic pain. Microglia-derived factors enable the activation of astrocytes. The complement component C1q, which promotes the activation of astrocytes, is known to be synthesized in microglia. However, it is unclear whether microglia-astrocyte communication via C1q is involved in orofacial neuropathic pain. Here, we analyzed microglia-astrocyte communication in a rat model with infraorbital nerve injury (IONI). The orofacial mechanical hypersensitivity induced by IONI was significantly attenuated by preemptive treatment with minocycline. Immunohistochemical analyses revealed that minocycline inhibited the increase in c-Fos immune-reactive (IR) cells and the fluorescence intensity of both Iba1 and glial fibrillary acidic protein (GFAP) in the Vc following IONI. Intracisternal administration of C1q caused orofacial mechanical hypersensitivity and an increase in the number of c-Fos-IR cells and fluorescence intensity of GFAP. C1q-induced orofacial mechanical hypersensitivity was completely abrogated by intracisternal administration of fluorocitrate. The present findings suggest that the enhancement in the excitability of Vc nociceptive neurons is produced by astrocytic activation via the signaling of C1q released from activated microglia in the Vc following IONI, resulting in persistent orofacial neuropathic pain.

Biofilm Formation Plays a Crucial Rule in the Initial Step of Carbon Steel Corrosion in Air and Water Environments.

In this study, we examined the relationship between the effect of a zinc coating on protecting carbon steel against biofilm formation in both air and water environments. SS400 carbon steel coupons were covered with a zinc thermal spray coating or copper thermal spray coating. Coated coupons were exposed to either air or water conditions. Following exposure, the surface conditions of each coupon were observed using optical microscopy, and quantitatively analyzed using an x-ray fluorescence analyzer. Debris on the surface of the coupons was used for biofilm analysis including crystal violet staining for quantification, Raman spectroscopic analysis for qualification, and microbiome analysis. The results showed that the zinc thermal spray coating significantly inhibited iron corrosion as well as biofilm formation in both air and water environments. The copper thermal spray coating, however, accelerated iron corrosion in both air and water environments, but accelerated biofilm formation only in a water environment. microbially-influenced-corrosion-related bacteria were barely detected on any coupons, whereas biofilms were detected on all coupons. To summarize these results, electrochemical corrosion is dominant in an air environment and microbially influenced corrosion is strongly involved in water corrosion. Additionally, biofilm formation plays a crucial rule in carbon steel corrosion in both air and water, even though microbially-influenced-corrosion-related bacteria are barely involved in this corrosion.

Cluster of differentiation 30 expression in lacrimal gland and conjunctival tissues in patients with Sjögren's syndrome: Case series.

INTRODUCTION: Sjögren's syndrome (SS) often causes lymphoproliferative disorders such as malignant lymphoma and macroglobrinemia. Approximately 5% of long-term follow-up SS patients develop malignant lymphoma. Recently, the tumor necrosis factor receptor superfamily cluster of differentiation 30 (CD30) has been thought to be implicated in malignant cells in organs affected by Hodgikin lymphoma or in a prognostic marker of diffuse large B cell lymphoma. In this study, we investigated CD30 expression in lacrimal gland and conjunctiva in patients with SS. METHODS: We examined lacrimal gland and conjunctival tissues for the diagnosis from 3 female SS patients with a median age of 51 and 3 female chronic graft-versus-host disease (cGVHD) patients with a median age of 41. Histological analysis of these tissues of the remaining samples was conducted by methods including immunohistochemistry and electron microscopy (#20090277). We analyzed the expression and localization of cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), cluster of differentiation 20 (CD20), CD30, and Interferon-γ in tissue sections prepared from lacrimal glands and conjunctiva in 3 each of SS and cGVHD patients. RESULTS: There were more B cells and plasma cells in lobules of SS-affected lacrimal glands than in those of their cGVHD-affected counterparts. Interferon-γ was expressed on endothelia of capillaries in SS-affected lacrimal gland and conjunctival tissues whereas it was expressed on fibroblasts in their GVHD-affected equivalents. Furthermore, lacrimal glands and conjunctiva disordered by SS had a greater number of CD30 cells than those disordered by cGVHD. CONCLUSION: Our results suggest that CD30 cells are increased in lacrimal glands and conjunctiva affected by SS and that a subset of SS patients are thereby at risk of development malignant lymphoma.

Microbiome Analysis of Biofilms of Silver Nanoparticle-Dispersed Silane-Based Coated Carbon Steel Using a Next-Generation Sequencing Technique.

Previously, we demonstrated that silver nanoparticle-dispersed silane-based coating could inhibit biofilm formation in conditions where seawater was used as a bacterial source and circulated in a closed laboratory biofilm reactor. However, it is still unclear whether the microbiome of a biofilm of silver nanoparticle-dispersed silane-based coating samples (Ag) differs from that of a biofilm of non-dispersed silane-based coating samples (Non-Ag). This study aimed to perform a microbiome analysis of the biofilms grown on the aforementioned coatings using a next-generation sequencing (NGS) technique. For this, a biofilm formation test was conducted by allowing seawater to flow through a closed laboratory biofilm reactor; subsequently, DNAs extracted from the biofilms of Ag and Non-Ag were used to prepare 16S rRNA amplicon libraries to analyze the microbiomes by NGS. Results of the operational taxonomy unit indicated that the biofilms of Non-Ag and Ag comprised one and no phyla of archaea, respectively, whereas Proteobacteria was the dominant phylum for both biofilms. Additionally, in both biofilms, Non-Ag and Ag, Marinomonas was the primary bacterial group involved in early stage biofilm formation, whereas Anaerospora was primarily involved in late-stage biofilm formation. These results indicate that silver nanoparticles will be unrelated to the bacterial composition of biofilms on the surface of silane-based coatings, while they control biofilm formation there.

Corneal Endothelial Regeneration Using Mesenchymal Stem Cells Derived from Human Umbilical Cord.

Corneal blindness is the third leading cause of blindness in the world, and one of the main etiologies is dysfunction of the corneal endothelium. Current treatment of corneal endothelial disease is allogenic corneal transplantation, which is limited by the global shortage of donor corneas and immunological rejection. The corneal endothelium consists of a monolayer of cells derived from the neural crest and mesoderm. Its main function is to prevent corneal edema by tight junctions formed by zonular occludens-1 (ZO-1) and Na, K-ATPase pump function. The human umbilical cord (UC) is a rich source of mesenchymal stem cells (MSCs). UC-MSCs that have multi-lineage potential may be an accessible allogenic source. After inducing differentiation with medium containing glycogen synthase kinase (GSK) 3-ß inhibitor, UC-MSCs formed polygonal corneal endothelial-like cells that functioned as tissue-engineered corneal endothelium (UTECE). Expressions of major corneal endothelial markers were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative RT-PCR (qRT-PCR). Western blotting confirmed the expression of Na,K-ATPase and PITX2, the functional and developmental markers of corneal endothelial cells. Immunohistochemistry revealed the localization of Na,K-ATPase and ZO-1 in cell-cell junctions, suggesting the presence of tight junctions. In vitro functional analysis revealed that UTECE had significantly high pump function compared with UC-MSCs. Moreover, UTECE transplanted into a rabbit model of bullous keratopathy successfully maintained corneal thickness and transparency. Our findings suggest that UTECE may be used as a source of allogenic cells for the treatment of corneal endothelial disease.

Clipping Surgery for Unruptured Middle Cerebral Artery Aneurysms.

Clipping surgeries for 139 consecutive unruptured middle cerebral aneurysms were performed between April 1991 and March 2014. Left hemiparesis occurred in one case (0.7 %). Transient symptoms arose in six patients due to perforator injury, arterial branch occlusion, damage to the venous system, or chronic subdural hematoma. Neither mortality nor decline in cognitive function was noted in this study. Clipping surgery for unruptured middle cerebral artery aneurysms can be done with minimal morbidity. However, meticulous management during the perioperative period as well as the use of modern technologies during the surgery, such as MEP monitoring and ICG videoangiography, are needed for safe and secure clipping surgery.

Aetiology-specific comparison of long-term outcome of deep anterior lamellar keratoplasty for corneal diseases.

AIMS: To evaluate the long-term outcome of deep anterior lamellar keratoplasty (DALK) for the treatment of herpetic keratitis, keratoconus, stromal scars and corneal dystrophies. METHODS: This retrospective consecutive case study includes 275 consecutive eyes of 254 patients who underwent DALK; 35 eyes with herpetic keratitis, 114 eyes with stromal scar, 93 eyes with keratoconus and 67 eyes with corneal dystrophy. Exclusion criteria included therapeutic DALK for the treatment of descemetocele or infectious keratitis, and eyes with limbal stem cell deficiency. Patients were examined at 1, 3 and 6 months, and 1, 3 and 5 years after DALK. Graft survival rate, best corrected visual acuity (BCVA), endothelial cell density (ECD) and postoperative complications were evaluated. RESULTS: The mean postoperative follow-up duration was 51±41 months. The graft survival rate of all subjects was 96.8% at 1 year, 89.9% at 3 years, 83.5% at 5 years and 74.1% at 10 years. At 6 months, BCVA significantly improved from 1.14±0.54 to 0.22±0.21 in the keratoconus group, from 1.13±0.60 to 0.44±0.54 in the herpes group, from 1.00±0.59 to 0.49±0.38 in the stromal scar group and from 1.04±0.52 to 0.32±0.29 in the corneal dystrophy group (all, p<0.0001). BCVA stabilised after 6 months thereafter up to 5 years. ECD decreased just after DALK and maintained >1000 cell/mm(2) at 5 years in all groups. CONCLUSIONS: DALK provides good visual acuity with slight ECD decrease over long term in all groups.

High-dose methotrexate monotherapy followed by radiation for CD30-positive, anaplastic lymphoma kinase-1-positive anaplastic large-cell lymphoma in the brain of a child.

The authors report the case of an 11-year-old immunocompetent boy with primary CNS CD30-positive anaplastic large-cell lymphoma (ALCL) that was also positive for anaplastic lymphoma kinase-1. His initial clinical manifestation was acute meningitis of unknown etiology. Findings on CT scanning were normal. Although he received empirical treatment against infection, his systemic and neurological status deteriorated. Subsequent MRI revealed newly emerged enhanced lesions and concomitant edema in the left parietal lobe. Diagnosis was confirmed following a brain biopsy and immunohistochemical staining. Three courses of systemic high-dose methotrexate (HD-MTX) treatment with 2-week intervals was started, followed by whole-brain radiation. His clinical course improved, and he has remained disease-free for more than 8 years without any additional treatment. Because ALCL originating in the brain is extremely rare and difficult to diagnose, no standard treatment has been established. This report suggests that systemic HD-MTX monotherapy can be an effective and worthwhile tailored therapeutic option for pediatric primary CNS ALCL.

Rakkyo fructan as a cryoprotectant for serum-free cryopreservation of mammalian cells.

Cryopreservation refers to the long-term storage of mammalian cells. Mammalian serum is generally used as a cryoprotectant, but is associated with problems including the risk of contamination by pathogens and quality control issues. Therefore, a serum-free cryopreservation method needs to be established. In this study, we focused on rakkyo fructan, a fructose polymer, derived from the Japanese shallot as an alternative factor to serum. Fructan contributes to tolerance to frost and dehydration in plants by stabilizing the plant membrane. However, whether fructan protects mammalian cells against freezing stress remains unknown. The ability of rakkyo fructan to be an alternative cryoprotectant to fetal bovine serum (FBS) was examined in the present study. 2E3-O, a mouse hybridoma, was preserved in rakkyo fructan, was highly viable after being defrosted, and then proliferated rapidly. When rakkyo fructan was combined with dimethylsulfoxide (DMSO), its ability to protect the hybridoma against freezing stress was improved. The rakkyo fructan and DMSO mixture was used in the cryopreservation of the mammalian cell lines CHO-DP12, a producer of recombinant antibodies, and HepG2, human hepatoma cells frequently tested in bio-artificial livers. Following the freezing and thawing processes, CHO-DP12 cells retained their ability to produce recombinant antibodies and as did HepG2 cells for albumin and mRNA expression of cytochrome P450 enzymes. These results indicate that rakkyo fructan is a promising cryoprotectant that prevents mammalian cells from freezing stress similar to FBS.

[Tuberculosis of the thyroid gland mimicking thyroid carcinoma in the elderly].

A 76-year-old woman with a 10-year history of chronic glomerulonephritis was treated at a clinic after presenting with a gradual worsening of the renal function. The patient had no history of tuberculosis. She was subsequently hospitalized for uremic symptoms and treated with internal shunt insertion and dialysis. Thyroid ultrasonography was performed to screen for secondary hyperparathyroidism, which revealed a calcified thyroid mass and cervical lymph node swelling. Fine-needle aspiration biopsy was thus conducted to assess suspected thyroid cancer. The cytological findings showed few follicular epithelial cells, without any signs of malignancy. However, a diagnosis of thyroid cancer continued to be strongly suspected based on the imaging features. Total thyroidectomy and bilateral cervical regional lymph node dissection were therefore performed, and the pathological examination of the thyroidectomy specimen disclosed scattered epithelioid granulomas with caseous necrosis in the entire right lobe as well as the cervical lymph nodes. Based on these findings, the patient was diagnosed with thyroid tuberculosis. As the symptoms and imaging findings of tuberculosis are nonspecific in elderly patients, it is necessary to consider this disease in this population. We therefore propose the inclusion of thyroid tuberculosis in the differential diagnosis of elderly patients who present with malignant thyroid tumors on aspiration biopsy cytology, regardless of whether or not they have a previous history of tuberculosis.

[Mucoepidermoid carcinoma of the intrahepatic bile duct with metastasis to the cranial skin].

Mucoepidermoid carcinoma of the intrahepatic bile duct is a rare variant of cholangiocarcinoma: it is composed of mucus-secreting squamous cells and glandular cells within the same nests. This tumor is very aggressive, with high-grade malignancy, and has a poor prognosis. In the international literature, only 17 cases of mucoepidermoid carcinoma originating in the hepatic bile duct system have been reported until now. We report an autopsy case of mucoepidermoid carcinoma of the intrahepatic bile duct with metastasis to the cranial skin in a Japanese man who was more than 70 years old. This cancer metastasizes to many organs, but skin metastasis is extremely rare.

[Characteristics and treatment of dural and perimedullary arteriovenous fistula at the craniocervical junction presenting with subarachnoid hemorrhage].

Dural and perimedullary arteriovenous fistula (AVF) at the craniocervical junction tend to cause subarachnoid hemorrhage (SAH). However, their natural history and clinical manifestations still remain to be elucidated. From 2003 to 2009, we encountered 5 cases of dural and perimedullary AVF presented with SAH. They were all male, ranging in age from 53 to 85 year-old (mean: 68 year-old). Rebleeding occurred in 1 patient on day 11. Outcome estimated by modified Rankin Scale did not change remarkably from 2.6 on admission to 2.4 at 3 months later on average. Cerebral angiography and 3D-CT angiography disclosed feeders originating from radicular or intracranial vertebral arteries which drained into the epidural venous plexus or spinal meningeal veins. One patient died of systemic complication during his clinical course. Thus we performed open surgery in the remaining 4 patients. Of these, we failed to occlude feeders completely in the initial surgery without intraoperative digital subtraction angiography (DSA) in 2 patients. Following this treatment we performed coil embolization and repeated open surgery with the aid of intraoperative DSA, respectively. In 1 patient out of the remaining 2 patients, we utilized intraoperative DSA to confirm complete disappearance of AVF composed of multiple feeders. These observations show that SAH caused by dural and perimedullary AVF at the craniocervical junction should be mainly treated by open surgery with the aid of intraoperative DSA in order to accomplish obliteration of the feeders because, otherwise, we might fail to confirm complete disappearance of AVF.

Delayed wound infection after supracricoid partial laryngectomy following failure of high dose radiation.

Past radiation therapy is known as a major risk factor promoting post-supracricoid partial laryngectomy (SCPL) complications. Risk of post-SCPL complications may further increase following failure of high dose radiation; in these patients, wound infection may become evident more than 1 month after an uneventful post-surgical course. By defining this complication as "Delayed Wound Infection" and reviewing the clinical features, we intended to elucidate the mechanism, risk factors, and management of this post-SCPL complication. Between 1997 and 2009, 60 patients received SCPL. The incidence of post-SCPL wound infection was analyzed in reflect to radiation status, radiation dose, and medical histories. Of 60 patients, delayed wound infection was identified in 4 (7%); radiation doses were 65, 68, 70, and 76.8 Gy (avg. 70 Gy). Blood data including white blood cell and C-reactive protein showed slight elevation before the delayed infection became evident. Patients with high dose radiation (≥ 65 Gy) accompanied by histories of diabetes and renal insufficiency are considered a high risk group. Delayed re-epithelialization of the inner surface of the cricohyoido gap was presumed to be the main pathogenesis. Early initiation of antibiotics and hyperbaric oxygen therapy are effective for rapid recovery. "Delayed Wound Infection" was treatable and patients undergoing surgery after failure of high dose radiation should be managed with extra precaution, but should not be excluded from the indications for SCPL.

Surgical procedure and results of cisternal washing therapy for the prevention of cerebral vasospasm following SAH.

In 1994, we started cisternal washing therapy (CWT) using urokinase combined with head-shaking method in order to prevent cerebral vasospasm. In this paper, we showed the surgical procedure for CWT and reported the effect of this therapy in preventing vasospasm following SAH. A total of 332 consecutive cases with Fisher group 3 SAH since 1988 were analyzed. Of these patients, 118 cases (56 cases before 1994 and 62 cases after 1994) had not CWT, and, 214 cases after 1994 had this therapy. All of these patients had clipping surgery within 3 days following SAH, and had postoperative management both with normovolemia and normal to mild hypertension. In these two groups, the incidence of symptomatic vasospasm (transiently symptomatic vasospasm without infarction), cerebral infarction due to vasospasm on CT, and mortality and morbidity (M&M) due to vasospasm were analyzed. In the group without CWT, the incidences of symptomatic vasospasm, cerebral infarction on CT, and M&M due to vasospasm were 4.2%, 28.8%, and 17.8%, respectively. On the other hand, in the group with CWT, they were 3.7%, 6.5%, and 2.8%, respectively. In the patients with CWT, the incidence of cerebral infarction on CT due to vasospasm and M&M due to vasospasm were significantly (p < 0.05) decreased. CWT was effective in preventing cerebral vasospasm.

Development of peptide arrays for detection of IgE-binding epitopes in cow's milk allergens.

Peptide arrays have become versatile tools for high throughput screening assays in biomedical and pharmaceutical research. In this study, we constructed a peptide array that contained linear peptide fragments reported as IgE-binding epitopes for cow's milk allergy (CMA). Various peptides with different solubility in aqueous solutions were dissolved in the buffer solutions containing sodium dodecyl sulfate, and we achieved a consistent spotting of peptide solutions using a piezoelectric ceramic micropump. The IgE-binding patterns were successfully detected by observing the binding of Alexa 647-labeled anti-human IgE using sera from CMA patients. Our technique in this study will provide a potent capability for the development of a peptide array for mapping IgE-epitopes in milk proteins, and it will help researchers better understand the IgE-epitopes associated with the clinical outcome of CMA.