Tracheobronchial Adenoid Cystic Carcinoma Treated Successfully With Chemoradiotherapy Followed by Durvalumab: A Case Report.

BACKGROUND/AIM: Tracheobronchial adenoid cystic carcinoma (ACC) is a rare type of malignancy. Although complete resection is standard treatment for localized ACC, treatment for unresectable ACC has not been established. It is unclear whether concurrent chemoradiotherapy (CCRT) followed by immune checkpoint inhibitor (ICI) therapy is effective for ACC. CASE REPORT: A 49-year-old man was admitted to our hospital for the treatment of dyspnea and thickening of the bronchial wall from the tracheal carina to the left main bronchus, as observed on a CT scan. Systemic examinations and transbronchial biopsy led to a diagnosis of locally advanced ACC. Although radiotherapy and chemotherapy are not regarded as very sensitive for ACC, a favorable response was obtained with CCRT. Following CCRT, he received ICI therapy with durvalumab for 1 year. The patient has remained in a stable condition 18 months after therapy, with no recurrence. CONCLUSION: ICI after CCRT might be a promising treatment option for unresectable tracheobronchial ACC.

Shift-and-add image processing incorporated with the unsharp masking method.

Shift-and-add (SAA) is a simple image processing procedure. SAA was devised to reconstruct a diffraction-limited image from atmospherically degraded stellar images. Recently SAA has been applied to biological imaging. There are several variants of SAA. Here proposed is an SAA procedure incorporated with unsharp masking (USM). The SAA procedure proposed here encompasses an extended version of USM. The proposed SAA method retains the simplicity and easiness, and the basic features of SAA. The effectiveness of the proposed method is examined by restoring atmospherically degraded solar images. It is shown that the USM SAA reconstructed image exhibits high contrast and reveals fine structures blurred by atmospheric turbulence. It is also shown that the USM SAA performs better with a data frame selection scheme.

Clinical application of autogenous partially demineralized dentin matrix prepared immediately after extraction for alveolar bone regeneration in implant dentistry: a pilot study.

The aim of this study was to examine the efficacy and safety of autogenous partially demineralized dentin matrix (APDDM) prepared onsite, for clinical application in bone regeneration procedures related to implant dentistry, including socket preservation, alveolar ridge augmentation, and maxillary sinus floor augmentation. In this study, 16 patients underwent dental implant placement using APDDM transplantation. There were no systemic or local complications (including surgical site infection) in any of the cases, and oral rehabilitation using dental implants was successful in all cases for at least 2 years after attachment of the suprastructure. This report describes the clinical application of APDDM prepared immediately after tooth extraction to bone augmentation, taking advantage of the relatively short preparation time due to partial demineralization. APDDM, as introduced in this study, is an efficient, safe, and reasonable bone substitute. Consequently, this material has the potential to become one of the options as a bone substitute in implant dentistry.

Clinical outcome after 36 months of treatment with injections of autologous blood for recurrent dislocation of the temporomandibular joint.

We investigated the prognosis after three years of treatment for recurrent dislocation of the temporomandibular joint with autologous blood given intravenously in 21 patients with a mean (range) age 64 (17-92) years of whom 16 had coexisting systemic disease. The mean (range) follow up from the first injection was 64 (41-99) months. Eighteen patients had no recurrence during the first 36 months after their first injection, which showed that this minimally-invasive treatment was effective, particularly for those who had conditions that made a mouthpiece or operation unsuitable.

Effect of GLP-1 receptor agonist on gastrointestinal tract motility and residue rates as evaluated by capsule endoscopy.

AIM: This study evaluated the effects of a glucagon-like peptide-1 receptor agonist on gastrointestinal (GI) tract motility and residue rates by examining GI transit time and lumen using capsule endoscopy. MATERIAL AND METHODS: GI motility and lumen were assessed by capsule endoscopy before and after liraglutide administration in 14 patients with type 2 diabetes mellitus (T2DM). RESULTS: Gastric transit time in the group with diabetic neuropathy (DN) was 1:12:36±1:04:30h before liraglutide administration and 0:48:40±0:32:52h after administration (nonsignificant difference, P=0.19). Gastric transit time in the non-DN group was 1:01:30±0:52:59h before administration and 2:33:29±1:37:24h after administration (significant increase, P=0.03). Duodenal and small intestine transit time in the DN group was 4:10:34±0:25:54h before and 6:38:42±3:52:42h after administration (not significant, P=0.09) and, in the non-DN group, 3:51:03±0:53:47h before and 6:45:31±2:41:36h after administration (significant increase, P=0.03). The GI residue rate in the DN group was 32.1±24% before administration and 90.0±9.1% after administration (significant increase, P<0.001), and increased in all patients; in the non-DN group, it was 32.1±35.3% before and 78.3±23.9% after administration (significant increase, P<0.001), and also increased in all patients. CONCLUSION: Liraglutide causes delayed gastric emptying and inhibits duodenal and small intestine motility. However, these GI movement-inhibiting effects may be decreased or absent in patients with DN-associated dysautonomia.

Administration of teriparatide improves the symptoms of advanced bisphosphonate-related osteonecrosis of the jaw: preliminary findings.

Teriparatide is a synthetic polypeptide hormone that contains the 1-34 amino acid fragment of the recombinant human parathyroid hormone that stimulates bone formation. Currently, it is approved only for the treatment of osteoporosis. The outcomes of daily teriparatide injections for the treatment of bisphosphonate-related osteonecrosis of the jaw in 10 patients are reported here. Two of the 10 cases dropped out due to adverse events. Of the remaining eight cases, seven exhibited clinical improvement of the jaw-related symptoms of osteonecrosis and progression of the sequestration, while one case did not show improvement of the symptoms. Administration of teriparatide in patients with osteonecrosis of the jaw promotes bone formation and subsequent sequestration over a short period of time. These results suggest that adjunctive teriparatide therapy is a viable and effective option for treating osteonecrosis of the jaw.

Review of renal tumors associated with Birt-Hogg-Dubé syndrome with focus on clinical and pathobiological aspects.

Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant inherited disorder characterized by clinical features of skin lesions, pulmonary lesions and renal tumor. The gene responsible for this syndrome is located on chromosome 17p11.2 and designated as FLCN. In this article, we review renal tumors associated with BHDS with a focus on clinical and pathobiological aspects. Renal tumors often occur multifocally or bilaterally in the imaging analyses or gross examination. Histological examination of renal tumors includes a variety of subtypes such as hybrid oncocytic tumor, chromophobe renal cell carcinoma (RCC), oncocytoma, clear cell RCC and papillary RCC. The histologic discordance in multiple tumors seems to be characteristic of this syndrome. Oncocytosis is observed histologically in about half of the cases. Several investigations have elucidated that folliculin may be involved in the mammalian target of rapamycin (mTOR) pathway recently. Renal tumors composed of clear cells may behave in an aggressive fashion. However, renal tumors including hybrid oncocytic tumor, chromophobe RCC and oncocytoma behave mostly in an indolent fashion.

Major change in regiospecificity for the exo-1,3-ß-glucanase from Candida albicans following its conversion to a glycosynthase.

The exo-1,3-ß-glucanase (Exg) from Candida albicans is involved in cell wall ß-d-glucan metabolism and morphogenesis through its hydrolase and transglycosidase activities. Previous work has shown that both these activities strongly favor ß-1,3-linkages. The E292S Exg variant displayed modest glycosynthase activity using α-d-glucopyranosyl fluoride (α-GlcF) as the donor and pNP-ß-d-glucopyranoside (pNPGlc) as the acceptor but surprisingly showed a marked preference for synthesizing ß-1,6-linked over ß-1,3- and ß-1,4-linked disaccharide products. With pNPXyl as the acceptor, the preference became ß-1,4 over ß-1,3. The crystal structure of the glycosynthase bound to both of its substrates, α-GlcF and pNPGlc, is the first such ternary complex structure to be determined. The results revealed that the donor bound in the -1 subsite, as expected, while the acceptor was oriented in the +1 subsite to facilitate ß-1,6-linkage, thereby supporting the results from solution studies. A second crystal structure containing the major product of glycosynthesis, pNP-gentiobiose, showed that the -1 subsite allows another docking position for the terminal sugar; i.e., one position is set up for catalysis, whereas the other is an intermediate stage prior to the displacement of water from the active site by the incoming sugar hydroxyls. The +1 subsite, an aromatic "clamp", permits several different sugar positions and orientations, including a 180° flip that explains the observed variable regiospecificity. The p-nitrophenyl group on the acceptor most likely influences the unexpectedly observed ß-1,6-specificity through its interaction with F229. These results demonstrate that tailoring the specificity of a particular glycosynthase depends not only on the chemical structure of the acceptor but also on understanding the structural basis of the promiscuity of the native enzyme.

Current-induced magnetic domain wall motion below intrinsic threshold triggered by Walker breakdown.

Controlling the position of a magnetic domain wall with electric current may allow for new types of non-volatile memory and logic devices. To be practical, however, the threshold current density necessary for domain wall motion must be reduced below present values. Intrinsic pinning due to magnetic anisotropy, as recently observed in perpendicularly magnetized Co/Ni nanowires, has been shown to give rise to an intrinsic current threshold J(th)(0). Here, we show that domain wall motion can be induced at current densities 40% below J(th)(0) when an external magnetic field of the order of the domain wall pinning field is applied. We observe that the velocity of the domain wall motion is the vector sum of current- and field-induced velocities, and that the domain wall can be driven against the direction of a magnetic field as large as 2,000 Oe, even at currents below J(th)(0). We show that this counterintuitive phenomenon is triggered by Walker breakdown, and that the additive velocities provide a unique way of simultaneously determining the spin polarization of current and the Gilbert damping constant.

Human papillomavirus type 56-associated Bowen disease.

BACKGROUND: Some cases of human papillomavirus (HPV) type 56 infection in Bowen disease have been reported. However, the incidence and clinical characteristics are still unclear. OBJECTIVE: To clarify the prevalence of HPV type 56-positive Bowen disease in our department and to characterize the clinical manifestations. METHODS: Sixty-eight specimens of Bowen disease were examined by polymerase chain reaction using HPV consensus primers, and the amplified products were subjected to DNA sequence analyses. Moreover, positive samples were investigated by in situ hybridization. These findings were used to clarify the clinical characteristics of HPV-positive Bowen disease. RESULTS: Eight out of 68 specimens (12%) of Bowen disease were HPV-positive, of which six specimens were HPV type 56-positive. The HPV type 56-positive lesions were characterized by a longitudinal melanonychia or a deeply pigmented keratotic lesion. The remaining two specimens were genital Bowen disease in which HPV type 16 was detected. In situ hybridization demonstrated the positive cells in the upper layer of epidermis. The HPV type 56 detected in the samples of longitudinal melanonychia can be divided into at least into two types. CONCLUSIONS: This study determined the prevalence of HPV type 56-positive Bowen disease. Longitudinal melanonychia is the most characteristic manifestation of HPV type 56-associated Bowen disease.

Feasibility of cytological diagnosis of sarcoidosis with endobronchial US-guided transbronchial aspiration.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has a high diagnostic value in sarcoidosis if the obtained histological specimen is indicative of a non-caseating epithelioid-cell granuloma. However, EBUS-TBNA in sacoidosis sometimes affords solely cytological specimens. OBJECTIVE: To investigate the relevance of EBUS-TBNA cytology specimens in diagnosing sarcoidosis. DESIGN: The study population comprised 72 patients with sarcoidosis and 116 patients who had thoracic malignancies and intrathoracic lymphadenopathy but were eventually proven to be metastasis-free (controls). The EBUS-TBNA samples obtained for these subjects were blindly evaluated for the presence of epithelioid cell clusters by 2 independent cytoscreeners and a pathologist. RESULTS: Interobserver variability in the specimen grading was minimal. The sensitivity and specificity were 65.3% and 94.0%, respectively. The sensitivity was high, at 87.5%, for the combined cytological and histological examinations. Of 7 controls whose cytological specimens showed epithelioid cell clusters, 3 were also deemed positive for sarcoidosis on histological examination, which indicated that they had sarcoid reaction to cancer. CONCLUSIONS: Cytological evaluation of the EBUS-TBNA specimens had higher sensitivity than histological evaluation alone for intrathoracic lymphadenopathy due to sarcoidosis. It should be recognized, however, that up to 6% of patients with thoracic malignancy may have sarcoid reaction in non-metastatic lymph nodes.

Simulation of deoxynivalenol intake from wheat consumption in Japan using the Monte Carlo method.

The aim of this study was to evaluate the current advisory level in Japan for deoxynivalenol (DON) in foods. To this end, we estimated the intake of DON based on its presence in wheat using a probabilistic computer simulation method. Values for the concentration of DON in wheat were based on those reported in surveys of 638 wheat samples conducted from 2002 to 2004. Data regarding consumption of 108 wheat-based products according to age group were obtained from the 2002 Japan national survey on food consumption. Two data sets on the consumption of wheat-based products and contamination of DON in wheat were analysed using three DON regulatory scenarios: no regulation, 1100 µg kg(-1) and 2000 µg kg(-1). Because consumption distributions contained two peaks for each age category, it was assumed that two log-normal distributions for each age category were needed to achieve a better fit to the distribution models. The results of simulated DON intake using the Monte Carlo method showed that children aged 1-6 years have the highest DON intake. However, the 95th percentile of simulated intake of DON in each age group was below the provisional maximum tolerable daily intake (TDI) of 1 µg kg(-1) body weight using any regulation scenario. The 99th percentile of simulated DON intake in the 1-6-year-old group was greater than TDI at approximately 2 µg kg(-1) body weight. These results suggest that the current dietary intake of DON from wheat consumption does not exert a significant health effect, but we may need to reconsider the current regulation value for the 1-6-year-old age group. In addition, we may need a better method to fit the distribution to the log-normal distribution better.

Observation of the intrinsic pinning of a magnetic domain wall in a ferromagnetic nanowire.

The spin transfer torque is essential for electrical magnetization switching. When a magnetic domain wall is driven by an electric current through an adiabatic spin torque, the theory predicts a threshold current even for a perfect wire without any extrinsic pinning. The experimental confirmation of this 'intrinsic pinning', however, has long been missing. Here, we give evidence that this intrinsic pinning determines the threshold, and thus that the adiabatic spin torque dominates the domain wall motion in a perpendicularly magnetized Co/Ni nanowire. The intrinsic nature manifests itself both in the field-independent threshold current and in the presence of its minimum on tuning the wire width. The demonstrated domain wall motion purely due to the adiabatic spin torque will serve to achieve robust operation and low energy consumption in spintronic devices.

Magnetization vector manipulation by electric fields.

Conventional semiconductor devices use electric fields to control conductivity, a scalar quantity, for information processing. In magnetic materials, the direction of magnetization, a vector quantity, is of fundamental importance. In magnetic data storage, magnetization is manipulated with a current-generated magnetic field (Oersted-Ampère field), and spin current is being studied for use in non-volatile magnetic memories. To make control of magnetization fully compatible with semiconductor devices, it is highly desirable to control magnetization using electric fields. Conventionally, this is achieved by means of magnetostriction produced by mechanically generated strain through the use of piezoelectricity. Multiferroics have been widely studied in an alternative approach where ferroelectricity is combined with ferromagnetism. Magnetic-field control of electric polarization has been reported in these multiferroics using the magnetoelectric effect, but the inverse effect-direct electrical control of magnetization-has not so far been observed. Here we show that the manipulation of magnetization can be achieved solely by electric fields in a ferromagnetic semiconductor, (Ga,Mn)As. The magnetic anisotropy, which determines the magnetization direction, depends on the charge carrier (hole) concentration in (Ga,Mn)As. By applying an electric field using a metal-insulator-semiconductor structure, the hole concentration and, thereby, the magnetic anisotropy can be controlled, allowing manipulation of the magnetization direction.

Detection of human papillomavirus type 56 in Bowen's disease involving the nail matrix.

BACKGROUND: As Bowen's disease of the nail apparatus is quite rare, there have been only a few reports on the prevalence of human papillomavirus (HPV) infection in this condition. OBJECTIVES: The purpose of this study was to clarify the association of HPV with this disease involving the nail apparatus. METHODS: Five patients with Bowen's disease of the nail apparatus were investigated clinically, virologically and histologically. Total DNAs extracted from excised skin lesions were analysed using polymerase chain reaction (PCR) for the presence of HPV DNA and the amplified products were subjected to DNA sequence analyses. Histological localization of HPV DNA was examined by in situ hybridization. RESULTS: In three of five patients, HPV was detected by PCR amplification, and subsequent sequence analyses of the PCR products showed the sequences of HPV type 56. A common clinical feature of the three HPV-positive patients was longitudinal melanonychia. In contrast, the two HPV-negative patients presented with a convex nail deformity and a periungual ulcerative lesion. In two of three positive cases, there was a silent point mutation in the L1 gene of each HPV. In the remaining one case, the nucleotide sequence was consistent with the consensus sequence of HPV 56. Sequence analyses of the E6 gene revealed the infection of different variants of HPV 56 among the three cases. The viral genomes were located in keratinocyte nuclei upon in situ hybridization. CONCLUSIONS: HPV 56 may be involved in the carcinogenesis of Bowen's disease affecting the nail matrix with longitudinal pigmentation.

Ganglioglioma originating in the cerebellum with a large cyst--a case report and review of the literature.

Here we report a rare case of cerebellar ganglioglioma accompanied by a large cyst, and present a review of the reported 28 cases with cerebellar ganglioglioma. An otherwise healthy 46-year-old woman complained of gradual headache and truncal ataxia. MRI revealed a huge cystic lesion with a mural nodule in the left cerebellar hemisphere. The tumor was resected totally. Histologically, it was composed of neuronal and glial elements, and was accordingly diagnosed as ganglioglioma.

Ca channel currents inhibited by serum from select patients with Guillain-Barré syndrome.

We performed an electrophysiological study demonstrating inhibition of spontaneous muscle action potentials within a coculture of rat muscle and spinal cord by exposure to serum, as well as purified IgG, from patients with the acute motor axonal neuropathy (AMAN) variant of Guillain-Barré syndrome (GBS). However, exposure to serum from two patients with the acute inflammatory demyelinating polyneuropathy (AIDP) form of GBS had no effect. Using a whole-cell recording technique, we then investigated the effects of serum and purified IgG from patients with GBS on voltage-dependent calcium channel (VDCC) currents in nerve growth factor-differentiated PC12 cells. Serum from patients with GBS (AMAN) inhibited VDCC currents in PC12 cells, which was fully reversible by washing with the bath solution. Similarly, purified IgG from the serum of two patients with GBS (AMAN) also inhibited VDCC currents in PC12 cells. In contrast, sera from patients with AIDP and healthy volunteers did not affect VDCC currents in PC12 cells. These results suggest that muscle weakness in some patients with GBS might be induced by inhibition of Ca2+ channel currents within motor nerve terminals.

How is epigenetic information on chromatin inherited after DNA replication?

Although most somatic cells have identical genetic information, gene expression profiles are quite distinct in each cell type. The gene expression profiles are considered to be determined mainly by chromatin-encoded epigenetic information that includes histone modifications, histone variants, and factors such as HP1 and polycomb group proteins that organize higher-ordered chromatin structures. To gain insights into how such epigenetic information on chromatin is inherited on daughter DNA strands after DNA replication, we have purified the preassembled form of histone H3 by immunoaffinity purification. The histone H3 complex contains the two histone H3-H4 chaperones CAF1 and ASF1. Surprisingly, the H3 complex also contains a pair of H3-H4 dimers. This observation is striking because histones H3-H4 are known to exist as tetramers in solution. Since histones H3-H4 in the predeposition complex exist as a dimer, this raises the possibility that the H3-H4 dimer in the complex pairs with a parental H3-H4 dimer, assembling the de novo-synthesized and parental H3-H4 dimers in the same nucleosome. Based on these results, we propose a semi-conservative model of nucleosome duplication, which allows for segregation of parental H3-H4 dimers with encoded epigenetic information evenly to daughter DNA strands.