Design and synthesis of strong root gravitropism inhibitors with no concomitant growth inhibition.

Herein, we describe a highly potent gravitropic bending inhibitor with no concomitant growth inhibition. Previously, we reported that (2Z,4E)-5-phenylpenta-2,4-dienoic acid (ku-76) selectively inhibits root gravitropic bending of lettuce radicles at 5 µM. Based on the structure-activity relationship study of ku-76 as a lead compound, we designed and synthesized various C4-substituted analogs of ku-76. Among the analogs, 4-phenylethynyl analog exhibited the highest potency for gravitropic bending inhibition, which was effective at only 0.01 µM. Remarkably, 4-phenylethynyl analog is much more potent than the known inhibitor, NPA. Substitution in the para position on the aromatic ring of 4-phenylethynyl group was tolerated without diminished activity. In addition, evaluation using Arabidopsis indicated that 4-phenylethynyl analog inhibits gravitropism by affecting auxin distribution in the root tips. Based on the effects on Arabidopsis phenotypes, 4-phenylethynyl analog may be a novel inhibitor that differs in action from the previously reported auxin transport inhibitors.

[Two cases of MPO-ANCA-positive otitis media associated with facial palsy].

We report two cases of otitis media positive for antimyeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) associated with facial palsy. Case 1: A 73-year-old man treated for 3 months for bilateral otitis media with effusion had left facial nerve palsy and deteriorated bone conduction hearing in both ears. Blood analysis showed elevated MPO-ANCA to 134 EU. Case 2: A 66-year-old woman treated for about one year for bilateral otitis media with effusion and fluctuating mixed hearing loss had bilateral facial nerve palsy and a blood test positive for MPO-ANCA at 67 EU. Both were diagnosed with otitis media caused by ANCA-related vasculitis. After prednisolone and cyclophosphamide administration for half a year, blood test results were negative for MPO-ANCA. Both recovered almost completely from facial nerve palsy and bone conductive hearing loss partially improved except in one hearing-impaired ear. ANCA-related vasculitis of the temporal bone should thus be considered in those with intractable otitis media and deteriorated bone conduction hearing before the occurrence of facial palsy.

Design and chemical synthesis of root gravitropism inhibitors: Bridged analogues of ku-76 have more potent activity.

Previously, we found (2Z,4E)-5-phenylpenta-2,4-dienoic acid (ku-76) to be a selective inhibitor of root gravitropic bending of lettuce radicles at 5 µM, with no concomitant growth inhibition, and revealed the structure-activity relationship in this inhibitory activity. The conformation of ku-76 is flexible owing to the open-chain structure of pentan-2,4-dienoic acid with freely rotating single bonds, and the (2Z)-alkene moiety may be isomerized by external factors. To develop more potent inhibitors and obtain insight into the target biomolecules, various analogues of ku-76, fixed through conformation and/or configuration, were synthesized and evaluated. Stereochemical fixation was effective in improving the potency of gravitropic bending inhibition. Finally, we found highly potent conformational and/or configurational analogues (ku-257, ku-294 and ku-308), that did not inhibit root growth. The inhibition of root curvature by these analogues was comparable to that of naptalam.

[Significant factors affecting the operation time for benign parotid tumor].

Tumors of the parotid gland are fairly frequent among head and neck tumors. Parotidectomy for benign tumors is necessary for diagnosis and therapy. Furthermore, acquiring the skill for this operation is a significant step in the training course of an otolaryngologist Thus, it is useful to analyze the operation time and determine the factors affecting it to evaluate the progress in the operation skill. To measure the operation time and determine the factors affecting it, 71 cases, including 43 cases of pleomorphic adenomas and 28 cases Warthin's tumor, were retrospectively reviewed to the determine if the operation time depended on the age, sex, operated side, presence of complications, BMI, bleeding volume, tumor size, tumor location, exposure of branches of the facial nerve, and experience of the surgeon. Multivariate analysis was used to determine the factors correlated with the operation time. The results revealed that the bleeding volume, tumor size, tumor location and experience of the surgeon were significantly correlated with the operation time, whereas age, sex, operated side, presentation of complications and BMI showed no correlation with the operation time. Furthermore, surgeons with the experience of operating 20-39 cases took almost the same time for the operation as the surgeon with the experience of operating more than 40 cases. Taken together, to shorten the operation time, the inexperienced surgeon should start with smaller tumors and surgery in the superficial lobe in the initial training period, and supervision by well-experienced supervised surgeons is required until 30-40 are undertaken.

Construction of dye-stapled Quenchbodies by photochemical crosslinking to antibody nucleotide-binding sites.

We successfully converted an antibody single-chain variable fragment and a full-sized antibody to Quenchbodies, which are a type of powerful fluorescent immunosensor, through ultraviolet-based photochemical crosslinking of an indole-3-butyric acid-conjugated fluorescent dye to the nucleotide-binding sites near the antigen-binding sites.

A case of solitary fibrous tumor arising from the palatine tonsil.

Solitary fibrous tumor (SFT) is a distinctive, relatively uncommon soft-tissue neoplasm that usually arises from the pleura. It occurs at various sites; head and neck lesions are very rare. While most of these tumors have a benign course, a small number have malignant potential. We describe a rare case of SFT arising from the left palatine tonsil in a 66-year-old Japanese woman. The mass was completely resected. Immunohistochemical studies were strongly positive for CD34 and bcl-2, mildly positive for phosphorylated protein kinase B and phosphorylated extracellular signal-regulated kinase 1/2, and negative for platelet-derived growth factor receptor alpha and p53. These findings suggested that this tumor was benign. The patient showed no evidence of recurrence during 2 years of follow-up. We believe that the candidate prognostic marker should be checked to distinguish malignant from benign SFTs.

Sublingual epidermoid cyst presenting with distinctive magnetic resonance imaging findings.

A case of sublingual epidermoid cyst presenting distinctive magnetic resonance imaging (MRI) findings is described. A 39-year-old man presented to our hospital with a three months progressive left submandibular swelling, difficulty moving his tongue, and snoring. Preoperative evaluation with MRI and fine needle aspiration cytology (FNAC) revealed that the heterogeneous cystic lesion contained the squamous cells, which is compatible with ectodermal tissue. The mass was located above the mylohyoid muscle and spread to the pharyngeal space. By considering the size, infection history, patient age, and location, the cyst was completely resected under general anesthesia via cervical approach without any complication. Histopathologically, the cyst wall was lined by stratified squamous epithelium with no skin appendage, suggesting an epidermoid cyst. Ultrasound (US), MRI and FNAC were very useful of the preoperative diagnosis for oral and sublingual lesion. The postoperative course was uneventful and without recurrence after 24 months. This case showed that epidermoid cysts formed the rarely heterogeneous cystic tumor and it underlined usefulness of preoperative diagnosis, such as US, MRI and FNAC for oral and sublingual tumor.

Two cases of spontaneous regression of congenital cholesteatomas.

Congenital cholesteatoma arises behind a normal, intact tympanic membrane and is most plausibly explained by the persistence of fetal epidermoid formation. It is generally accepted that cholesteatoma in children has greater aggressive growth activity than that in adults. The congenital type of cholesteatoma starts as a small pearl in the middle ear and eventually grows to involve the ossicles and then the attic and mastoid, causing varying degrees of destruction and functional impairment. However, here we report the cases of two children with congenital cholesteatoma which disappeared spontaneously during the follow-up period. To the best of our knowledge, this is the first report on the spontaneous regression of congenital cholesteatoma. On the basis of the two cases, we could take a "wait and watch" attitude for congenital cholesteatoma in the absence of severe infection, hearing loss, or bone destruction in the middle ear.

Atypical carcinoid of the larynx and expressions of proteins associated with molecular targeted therapy.

OBJECTIVE: We reported an extremely rare case of atypical laryngeal carcinoid, and examined the expression of several proteins for application of molecular targeted therapy. METHOD: Case report and review of the literature concerning atypical carcinoid arising from the larynx. The expressions of proteins were determined by immunohistochemical analysis. RESULTS: We present here a case of atypical laryngeal carcinoid in a 79-year-old Japanese man, which was completely resected, and with no evidence of recurrence. On immunohistochemical analysis, neoplastic elements revealed, strong positivity for platelet-derived growth factor receptor α (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2), and epidermal growth factor receptor (EGFR), and were mild positivity for KIT. CONCLUSION: Our findings suggest that atypical laryngeal carcinoid could be completely removed if it is located in the limited lesion. PDGFRα, VEGFR2, and EGFR expressions in this case provide the evidence that atypical laryngeal carcinoid is the candidate for molecular targeted therapy, although further investigations are necessary.

A case of multiple abnormalities with eustachian tube obstruction by a protruded internal carotid artery.

We report a case of multiple abnormalities with eustachian tube obstruction by a protruded internal carotid artery. A 10-year-old male presented with multiple abnormalities including anomalous pinna, poor eyesight, facial palsy, moderate conductive deafness, and otitis media with effusion. Temporal bone computed tomography demonstrated obstruction of the right eustachian tube by a protruded internal carotid artery. Insertion of a tympanostomy tube did not improve his hearing, indicating a possible ossicular chain anomaly. Although tympanoplasty is necessary to improve the patients' hearing, the poor drainage function makes this difficult. Knowledge of this vascular anomaly is important when performing myringotomy or tympanoplasty.