Masayuki Minamino

Histamine-induced Calcium Released from Cultured Human Mucosal Microvascular Endothelial Cells from Nasal Inferior Turbinate

Changes in cytosolic Ca2+ concentration ([Ca2+]i) in cultured human mucosal microvascular endothelial cells (HMMECs) from nasal inferior turbinate were measured using a fluorescent Ca(2+)-sensitive dye, fura-2, and photometric fluorescence microscopy. Histamine caused a transient increase in intracellular free Ca2+ in cell populations and in individual cells, followed by a decrease to a sustained elevation. Histamine (100 microM) elevated [Ca2+]i in HMMECs up to 563 +/- 20 nM from a resting level of 60 +/- 45 nM (means +/- SD, n = 31). Promethazine (a histamine H1 receptor antagonist) inhibited [Ca2+]i increase during histamine stimulation, whereas cimetidine (a H2 receptor antagonist) and thioperamide (a H3 receptor antagonist) showed no inhibition. These results suggest that the histamine increase [Ca2+]i in HMMECs induces both a Ca2+ release from stores and a Ca2+ influx through activation of the H1 receptor.

Effects of protein kinase and phosphatase inhibitors on slow shortening of guinea pig cochlear outer hair cells.

The intracellular mechanisms of slow shortening in isolated guinea pig cochlear outer hair cells were investigated using inhibitors and/or an activator of protein kinases and protein phosphatases. The slow shortening was induced by tetanic electrical field stimulation, and changes in the cell length, volume and intracellular Cl- concentration were microscopically monitored using a chloride-sensitive fluorescent dye. The slow shortening was inhibited by a calmodulin inhibitor, W-7, and a calcium calmodulin-dependent protein kinase II (CaMKII) inhibitor, KN-62. The inhibition by W-7 or KN-62, was abolished by the supplemented conductance of K+ with valinomycin. Among the protein phosphatase inhibitors tested, a type 1 and 2A protein phosphatase inhibitor, calyculin A, inhibited the slow shortening. The inhibition by calyculin A was abolished by the increased Cl- permeability, but neither by the increased K+ conductance with valinomycin nor by the increased Ca2+ conductance with A23187. A protein serine/threonine phosphatase activator, N-acetylsphingosine, inhibited the shortening, which was abolished by either valinomycin or a type 2A protein phosphatase inhibitor, okadaic acid, but not by calyculin A. These findings suggest the following signaling mechanisms in the slow shortening of outer hair cells; the K+ channel opening is facilitated through protein phosphorylation by CaMKII and suppressed via okadaic acid-sensitive dephosphorylation, and the Cl- channel opening depends on calyculin A-sensitive protein phosphatase activity.

Local injection of OK-432/Fibrinogen gel into head and neck carcinomas

Immunotherapy with biological response modifiers (BRM) is a possible strategy against head and neck solid tumours. However, the rapid disappearance of BRM from the tumour area is one of the reasons for its limited clinical application. In this pilot study, fibrinogen gel containing OK-432 (a compound composed of attenuated Streptococcus pyogenes), an inducer of natural killer cells and T-cell cytotoxity, was injected directly into head and neck solid tumours of 15 patients. A dose of 5 Klinische Einheiten (KE) of OK-432 was reconstituted in 1 ml aprotinin and mixed with fibrinogen, the latter to maintain the OK-432 locally. 3 patients showed tumour regression, and in addition, we observed histological changes in the injected tumour of all patients. These results suggest that OK-432/fibrinogen gel generates a local immune response, leading to tumour regression.

Neurofibromatosis type 2 associated with cranial nerve schwannomas

on chromosome 221 and is characterized by the bilateral occurrence of vestibular schwannoma on the eighth cranial nerve.2 Although this disease has been demonstrated to be associated with several complications, such as intracranial neurogenic tumors, spinal tumors, and presenile lens opacities,3-5 it has not to our knowledge been reported to be accompanied by cervical schwannoma derived from cranial nerves. In this report we suggest the occurrence of cervical schwannoma in patients with NF2 by demonstrating 2 such cases involving cervical schwannoma derived from the vagal or hypoglossal cranial nerve.

A Case of Polyostotoic Fibrous Dysplasia

We report a 47-year-old woman with polyostotic fibrous dysplasia. She complained of a painless swelling of the left cheek since she was two years old. A craniofacial CT examination showed sclerotic changes of the left maxilla, sphenoid and temporal bone. Bone scintigraphy showed high uptakes at not only these craniofacial bones but also thoracic vertebrae, rib, left humerus and pelvis. A biopsy of the left maxilla bone was performed, and a histopathological examination showed fibrous dysplasia. Therefore, we diagnosed her as having polyostotic fibrous dysplasia. At present, the left maxillary tumor has not progressed. We are continuing careful follow-up.

Squamous Cell Carcinoma in Thyroid Papillary Carcinoma.

We report the case of a 62-year-old man with a Squamous cell carcinoma of the thyroid gland which had invaded the hypopharynx. Primary squamous cell carcinoma of the thyroid gland is extremely rare. Its clinical course is very aggressive and the prognosis is poor. The patient underwent a radical resection of the thyroid, hypopharynx, larynx and resection of the trachea and esophagus was conducted concomitantly with bilateral neck dissection. Reconstruction of the terminal tracheostomy in the anterior mediastinum was created using a pectoralis major muscle flap.

Clinical Studies of Oral Cancer.

Seventy-three cases of oral cancer (tongue: 47, oral floor: 10, buccal mucosa: 10, gingiva: 4, hard palate: 2) treatedinitially from 1985 to 1995 were reviewed retrospectively. The cumulative five year survival rate was 71.4% for all of the patients, and 75.8% for carcinomas of the tongue, 88.9% for carcinomas of the buccal mucosa and 42.2% for carcinomas of the oral floor. Further strategies are required in advanced cases with T4 staging in order to improve the survival rate and quality of life of oral cancer patients.

Cervical Thymic Cyst.

A case of cervical thymic cyst is presented, and the literature is reviewed. A 25-year-old-female was found to have a frontal neck mass. At surgery, the thyroid gland was found to be normal, but displaced by a cystic mass. The cyst was lobulated and contain clear fluid. It was removed from the carotid laterally and from the trachea medially.Thymic cysts are unusual neck masses that may occur along the embryologic pathway of migration of the thymus. The mass produces few symptoms, but can sometimes cause air way obstruction. Treatment consists of excision of the cyst and prognosis is usually good. This entity should be included in the differential diagnosis of neck masses.

Malignant Fibrous Histiocytoma of the Submental Region.

Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma in adults. The head and neck are unusual sites for primary MFH, and MFH of the submental region is extremely rare. We encountered a case of MFH in a 60-year-old man who initially showed swelling in the submental region. He died of distant metastasis to lung 15 months after the radical surgery and postoperative chemotherapy.The clinical course and prognosis in this case were described, and the literature was reviewed and discussed.