Effect of Azelastine Hydrochloride on Macrophage Chemotaxis and Phagocytosis in Vitro

Azelastine, a newly synthesized anti-allergic agent, was tested for its effects on guinea pig macrophage chemotaxis and phagocytosis. As specific macrophage chemo-attractants, we used macrophage chemotactic factors a and c; separated and highly purified from inflamed skin sites. Macrophage chemotaxis induced by skin extract or chemotactic factors was significantly suppressed by a low concentration of the agent (1 microgram/ml); the effect was dose-dependent. The inhibition of chemotaxis was reversible, because chemotactic activity was restored when the agents was removed by washing cells before chemotactic assay. Inactivation of chemotactic factors was not detected by mixing azelastine and factors a and c. Azelastine may directly interact with macrophages to decrease their chemotactic responsiveness. beta-Glucuronidase activity in the medium and macrophages after phagocytosis of polystyrene latex particles was not affected by this agent at concentrations ranging from 1 to 10 micrograms/ml. The phagocytosis of latex particles or sheep red blood cells opsonized with IgG antibodies (EA) and anchoring of macrophages to substrate were not inhibited and azelastine did not damage the macrophages as determined by lactate dehydrogenase (LDH) release assay.     

Cdc7 kinase is required for postnatal brain development

The evolutionally conserved Cdc7 kinase plays crucial roles in initiation of DNA replication as well as in other chromosomal events. To examine the roles of Cdc7 in brain development, we have generated mice carrying Cdc7 knockout in neural stem cells by using Nestin-Cre. The Cdc7^Fl/Fl Nestin^Cre mice were born, but exhibited severe growth retardation and impaired postnatal brain development. These mice exhibited motor dysfunction within 9 days after birth and did not survive for more than 19 days. The cerebral cortical layer formation was impaired, although the cortical cell numbers were not altered in the mutant. In the cerebellum undergoing hypoplasia, granule cells (CGC) decreased in number in Cdc7^{Fl/F l}Nestin^Cre mice compared to the control at E15-18, suggesting that Cdc7 is required for DNA replication and cell proliferation of CGC at mid embryonic stage (before embryonic day 15). On the other hand, the Purkinje cell numbers were not altered but its layer formation was impaired in the mutant. These results indicate differential roles of Cdc7 in DNA replication/cell proliferation in brain. Furthermore, the defects of layer formation suggest a possibility that Cdc7 may play an additional role in cell migration during neural development.     

A role for histamine in human-malignant glioma-cells

Histaminergic neuron cells send fiber terminals to almost all parts of the brain, and the histamine receptors on astrocytes are the main targets of central histaminergic neurons. But no proof of the significance of histamine and its specific receptors on human malignant astrocytoma cells has been presented to date. Our results show that six malignant glioma cell lines used in this experiment secreted histamine into the culture medium and that the histamine stimulated their DNA synthesis in a dose-dependent manner. Moreover, histamine induced accumulation of inositol triphosphate (IP3) in all cell lines in either a time- or a dose-dependent manner, whereas cAMP accumulation was not induced by it in any of these cell lines, indicating that these cell lines express the H-1-receptors but not the H-2-receptors. In vivo, thus, malignant glioma may possibly produce histamine, which then would stimulate their neoplastic behavior mediated by the H-1-receptor.     

Twelve cases of jugular foramen neurinoma

Twelve patients with jugular foramen neurinoma were operated on at our clinic between 1974 and 1990. The initial signs and symptoms were variable; dysfunctions of the 7th, 8th, 9th, 10th, and 11th nerves were frequently observed. Among these, involvement of the eighth nerve was most frequent, and three patients were given a misdiagnosis of acoustic neurinoma. Computed tomography scan and magnetic resonance imaging were useful not only for the correct diagnosis, but also for planning the surgical treatment and postoperative followup. Surgical resection was accomplished with four different approaches: (1) suboccipital approach without opening the jugular foramen, (2) suboccipital approach with opening the jugular foramen, (3) suboccipital approach with opening the jugular foramen combined with infralabyrinthine approach, (4) infralabyrinthine approach. The surgical approach depended on the presence of intracranial tumor and on the extent of extracranial involvement. There was no operative mortality. Dysfunction of the 8th, 9th, 10th, or 11th nerve did not improve in any patient after tumor removal. In contrast, 12th nerve palsy improved in two of three patients after tumor removal. The nerve of origin was identified in five cases; those were from the ninth nerve in three and from the 11th nerve in two.     

Cerebrospinal fluid beta(2)-microglobulin in neuro-Behçet's syndrome

Paired serum and cerebrospinal fluid (CSF) specimens from 17 patients with Beh?et's disease and central nervous system (CNS) involvement (neuro-Beh?et's syndrome; NB) were studied for beta(2)-microglobulin (beta(2)MG) and albumin, using ELISA and single radial immunodiffusion, respectively. We also studied 29 patients with non-inflammatory neurological diseases for comparison. All of CSF beta(2)MG, serum beta(2)MG, Q albumin (an indicator of blood-brain barrier function), and CSF beta(2)MG index (an indicator of intrathecal beta(2)MG synthesis) were significantly elevated in patients with NB compared with the control patients. There were no significant differences in these parameters between 11 patients with chronic NB and six patients with acute NB. In nine patients with NB, CSF beta(2)MG and Q albumin were significantly decreased when the CNS manifestations were improved by successful treatment, whereas CSF beta(2)MG index and serum beta(2)MG were not significantly changed. The results indicate that the elevation of CSF beta(2)MG, which results from the transudation of serum beta(2)MG as well as the increased intrathecal synthesis presumably by infiltrating lymphocytes, is a good marker of CNS disease activity of NB. The data, however, also suggest that the intrathecal synthesis of beta(2)MG might not parallel to the CNS disease activity of NB, most likely due to the recovery of constitutive physiological intrathecal synthesis of beta(2)MG in spite of the withdrawal of pathological beta(2)MG synthesis at times of treatment-associated improvement.     

Metastasis to the iris in squamous cell lung cancer

A 72-year-old Japanese woman, suffering from squamous cell lung cancer with brain metastasis, underwent 2 courses of combination chemotherapy, consisting of cisplatin and vindesine. Although both the primary tumor and the brain metastasis regressed markedly, she developed left ocular pain with blurred vision. An abnormal mass was found in the left iris, and cytologic examination of the aqueous aspirate revealed a few malignant cells, which, when examined by electron microscopy, were considered to be derived from squamous cell carcinoma of the lung.     

Herbimycin A Suppresses the Reduction of Gap-junctional Intercellular Communication Induced by Tumor-promoting Phorbol Ester in 3T3-L1 Cells

We have examined the suppressive effect of herbimycin A on the reduction of gap-junctional Intercellular communication that is induced by a tumor-promoting phorbol ester in 3T3-L1 cells. Most cells in growth arrest participated in dye-coupling, as evaluated by the transfer between cells of a fluorescent dye (Lucifer Yellow CH). Treatment of cells with 0.25 μg/ml herbimycin A slightly enhanced the dye-coupling. This enhancement required treatment for periods as long as 24 h. Addition of 100 ng/ml 12-O-tetradecanoylphorbol-13-acetate (TPA) caused a rapid reduction of dye-coupling. However, addition of TPA did not suppress dye-coupling in cells pretreated for more than 24 h with herbimycin A. Pretreatment of cells for less than 6 h with herbimycin A did not suppress the TPA-induced reduction of dye-coupling. These results suggest that herbimycin A suppresses the reduction of gap-junctional intercellular communication that is induced by TPA through enhancement of the ability of the cells to participate in gap-junctional intercellular communication     

A questionnaire about radiation safety management of the draining-water system at nuclear medicine facilities

We conducted a questionnaire survey about radiation-safety management condition in Japanese nuclear medicine facilities to make materials of proposition for more reasonable management of medical radioactive waste. We distributed a questionnaire to institutions equipped with Nuclear Medicine facilities. Of 1,125 institutions, 642 institutes (52.8%) returned effective answers. The questionnaire covered the following areas: 1) scale of an institution, 2) presence of enforcement of radiotherapy, 3) system of a tank, 4) size and number of each tank, 5) a form of draining-water system, 6) a displacement in a radioactive rays management area, 7) a measurement method of the concentration of medical radioactive waste in draining water system, 8) planned and used quantity of radioisotopes for medical examination and treatment, 9) an average displacement of hospital for one month. In most institutions, a ratio of dose limitation of radioisotope in draining-water system was less than 1.0, defined as an upper limitation in ordinance. In 499 hospitals without facilities of hospitalization for unsealed radioisotope therapy, 473 hospitals reported that sum of ratios of dose limits in a draining-water system was less than 1.0. It was calculated by used dose of radioisotope and monthly displacement from hospital, on the premise that all used radioisotope entered in the general draining-water system. When a drainage including radioactivity from a controlled area join with that from other area before it flows out of a institution, it may be diluted and its radioactive concentration should be less than its upper limitation defined in the rule. Especially, in all institutions with a monthly displacement of more than 25,000 m3, the sum of ratio of the concentration of each radionuclide to the concentration limit dose calculated by used dose of radioisotope, indicated less than 1.0.     

Repair of cervical esophageal perforation using longus colli muscle flap: a case report of a patient with cervical spinal cord injury

BACKGROUND CONTEXT: Perforation of the esophagus after anterior cervical spine surgery is a rare, but well-recognized complication. The management of esophageal perforation is controversial, and either nonoperative or operative treatment can be selected. PURPOSE: Several reports have described the use of a sternocleidomastoid muscle flap for esophageal repair. In this case report, we describe a longus colli muscle flap as a substitute for a sternocleidomastoid flap in a patient with an esophageal perforation. STUDY DESIGN: Case report. PATIENT SAMPLE: A 20-year-old man sustained cervical spinal cord injury, on diving and hitting his head against the bottom of a pool. A C6 burst fracture was observed with posterior displacement of a bone fragment into the spinal canal. The patient exhibited complete paralysis below the C8 spinal segment level. METHODS: The patient underwent subtotal corpectomy of the sixth cervical vertebra with the iliac bone graft and augmented posterior spinal fixation (C5-7) with pedicle screws. After the primary operation, the patient showed signs of infection such as throat pain, a high fever, and osteolytic change of the grafted bone by cervical radiograph. A second operation was performed to replace the graft bone using fibula. On the day after the operation, food residue was confirmed in the suction drainage tube, suggesting esophagus perforation. A third operation was immediately performed to confirm and treat esophagus perforation, although apparent esophageal perforation could not be detected at the second operation. Because the erosion around the perforation of the esophageal posterior wall was extensive, a longus colli muscle flap transposition was accordingly performed into the interspace between the esophageal posterior wall and the grafted bone in addition to simple suturing of the perforation. RESULTS: Neither high fever nor pharyngeal pain has recurred at latest follow-up, 5 years after surgery. CONCLUSIONS: To the best of our knowledge, this is the first report concerning the use of a longus colli muscle flap for esophageal perforation after anterior cervical spine surgery.