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.

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.

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.

Relationship between postoperative aeration around the stapes and postoperative hearing outcome after canal wall down tympanoplasty with canal reconstruction for cholesteatoma.

OBJECTIVES: To evaluate the correlation between postoperative aeration around the stapes and hearing outcome after canal wall down tympanoplasty with canal reconstruction for cholesteatoma. STUDY DESIGN: Retrospective case review. SETTING: University hospital otolaryngology department. PATIENTS: Seventy ears of 65 patients with middle ear cholesteatoma were included. Patients who had fixed or poorly mobile ossicular chain was excluded. INTERVENTIONS: They were underwent canal wall down tympanoplasty with canal reconstruction. Canal wall was reconstructed with the tragal or conchal cartilage and the cortical bone plate. MAIN OUTCOME MEASURES: We measured aeration around the stapes on coronal and axial computed tomographic sections at 1 year after ossiculoplasty and investigated the correlation between postoperative aeration around the stapes and postoperative air-bone gap (using the mean of 0.5-, 1-, and 2-kHz threshold values) at 1 year after ossiculoplasty. We also investigated it for each of Wullstein type and for each of 0.25-, 0.5-, 1-, 2-, and 4-kHz thresholds. RESULTS: Aeration around the stapes was negatively correlated with postoperative air-bone gap (correlation coefficient, -0.53; p < 0.05). Types I and IV tympanoplasty had a higher correlation with postoperative air-bone gap than type III tympanoplasty. The 0.5-KHz frequency had a higher correlation with postoperative air bone gap than other frequencies. CONCLUSION: Measurement of postoperative aeration around the stapes is an effective method for evaluating the importance of middle ear aeration. Aeration around the stapes contributes to better hearing outcome.

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.

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.

[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.

Eosinophilic inflammation in the middle ear induces deterioration of bone-conduction hearing level in patients with eosinophilic otitis media.

OBJECTIVE: Eosinophilic otitis media (EOM) is characterized by the extensive accumulation of eosinophils in the middle ear mucosa and middle ear effusion and is usually associated with bronchial asthma. Eosinophilic otitis media patients show gradual or sudden deterioration of hearing. In our previous study, we reported that high-tone loss was more frequently found and more severe in EOM patients than in control patients with chronic otitis media. These findings suggest that not only bacterial infection but also eosinophilic inflammation in the middle ear may damage the inner ear. The present study was performed to determine whether eosinophilic inflammation is indeed related to deterioration of bone-conduction hearing level (BCHL). PATIENTS: Fifty-five ears of 28 patients with EOM associated with bronchial asthma were included in this study. Middle ear effusion (MEE) samples were collected from all the patients, and the concentrations of eosinophilic cationic protein (ECP) and immunoglobulin E (IgE) were measured by fluorescence enzyme immunoassay. The BCHLs at 2 and 4 kHz for the worse-hearing ear of each patient were correlated with the concentrations of ECP and IgE. RESULTS: The concentration of IgE in MEE significantly and positively correlated with BCHL at 2 and 4 kHz. The ears with a higher concentration of ECP in MEE also tended to show deterioration of BCHL at 4 kHz. Other clinical risk factors for BCHL deterioration were male sex, long duration of EOM, association with bacterial infection, severe inflammatory changes of the middle ear mucosa, and high serum IgE concentration. CONCLUSION: Eosinophilic-inflammation-related substances such as ECP and IgE are closely related to the deterioration of BCHL at high frequencies. Particularly, IgE concentration in MEE is a good indicator of BCHL elevation. We should always pay attention to the hearing acuity of EOM patients with the risk factors.

Bone conduction hearing level in patients with eosinophilic otitis media associated with bronchial asthma.

OBJECTIVE: Eosinophilic otitis media (EOM) is characterized by the extensive accumulation of eosinophils in the middle ear mucosa and middle ear effusion and is usually associated with bronchial asthma. EOM patients show gradual deterioration of hearing and sometimes become deaf suddenly. However, there have been no systemic studies of bone conduction hearing level (BCHL) of patients with EOM. PATIENTS: Seventy-one ears of 38 patients with EOM associated with bronchial asthma were included in this study. For controls, 65 ears of age-matched 60 patients with chronic otitis media (COM), who underwent tympanoplasty, were similarly studied. The BCHLs at 250, 500, 1,000, 2,000 and 4,000 Hz of EOM patients were compared with those of COM patients, and the clinical risk factors for the deterioration of BCHL in EOM were analyzed. RESULTS: Two patients became profoundly deaf unilaterally after the onset of EOM. High-tone loss was more frequently found and more severe in EOM patients than in COM patients. The clinical risk factors for high-tone loss were older age, male sex, presence of pathogens, and condition of the middle ear mucosa. CONCLUSION: High-tone hearing loss and profound hearing loss were frequently associated with EOM, suggesting that inflammatory products of the middle ear invade the inner ear via the round window to cause inner ear damage. To prevent the deterioration of BCHL, the control of eosinophilic inflammation and bacterial infection is mandatory.

[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.