Attenuation of benzodiazepine-induced passive avoidance deficit by post-training administration of muscimol: interaction with the cholinergic neuronal system

We examined the involvement of GABAergic neuronal systems in benzodiazepine-induced passive avoidance deficit. Chlordiazepoxide impaired the passive avoidance response dose dependently when it was given prior to training. Post-training administration of muscimol improved the performance of chlordiazepoxide-pretreated mice. The effects of muscimol were antagonized completely by the GABAA antagonist, bicuculline, and the muscarinic acetylcholine receptor antagonist, scopolamine, but not by the benzodiazepine receptor antagonist, flumazenil, when the latter was administered immediately after training. It appears from these results that the GABAergic neuronal system plays an important role in the benzodiazepine-induced passive avoidance deficit by interacting with the cholinergic neuronal system.     

Effects of DM-9384, a pyrrolidone derivative, on alcohol- and chlordiazepoxide-induced amnesia in mice

The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide (DM-9384), a new pyrrolidone derivative, were investigated on ethanol- and chlordiazepoxide (CDP)-induced amnesia animal model using the passive avoidance task in comparison with aniracetam, another pyrrolidone derivative. Pretraining administration of DM-9384 attenuated ethanol- and CDP-induced amnesia, whereas aniracetam failed to do so. The effects of DM-9384 on CDP-induced amnesia were antagonized by bicuculline, a GABAA receptor antagonist, but not by scopolamine, a muscarinic acetylcholine receptor antagonist and flumazenil, a benzodiazepine receptor antagonist. These results suggest that DM-9384 attenuates CDP-induced amnesia by interacting with the GABAergic neuronal system.     

Effects of vinconate, a novel vinca alkaloid, on spatial learning deficits induced by the basal forebrain lesion in rats.

We investigated the effects of vinconate, a novel vinca alkaloid, on spatial learning deficits induced by the basal forebrain (BF) lesion in rats. Bilateral BF lesions were produced by injecting ibotenic acid (6 micrograms/0.5 microliter/side). In BF-lesioned rats, impairment of spatial learning in escaping onto the platform during training and decrease in spatial bias during the spatial probe trial in Morris's water maze task were both observed. Vinconate (5 and 10 mg/kg) treatment shortened the increase of escape latency to the platform in BF-lesioned rats and significantly reversed the decrease in spatial bias induced by the BF lesion. Vinconate (10 mg/kg) attenuated the decrease in choline acetyltransferase activity in the frontoparietal cortex caused by the BF lesion. The present study suggests that vinconate has an antiamnesic effect on the BF-lesion-induced amnesia by ameliorating the dysfunction in cholinergic neurons.     

Behavioral pharmacological action of Ca-4-(3,5-dihydroxy-3-methylpenthylamido) butyrate (mevalonic GABA, MV-GABA)

The behavioral pharmacological effects of Ca-4-(3,5-dihydroxy-3-methylpenthylamido) butyrate (mevalonic-GABA, MV-GABA), a new GABA derivative were studied in comparison with those of Ca-hopantenate (HOPA) in mice. MV-GABA had no effect on the general behavior and electric shock-induced fighting behavior. The dosage of MV-GABA which caused locomotor hypoactivity produced an impairment of the rotarod performance. MV-GABA inhibited the hyperactivity induced by a dopamine (DA) agonist (methamphetamine) and acetylcholine (ACh) antagonists (scopolamine and atropine) at a dose which did not affect locomotor activity in normal mice. MV-GABA prolonged the pentobarbital-Na-induced sleeping time, and it prolonged the latencies until convulsion and death after administration of strychnine. MV-GABA and HOPA antagonized the electroconvulsive shock-induced amnesia in the passive avoidance response of mice. These results suggest that MV-GABA has effects on the central nervous systems, in particular, ACh and DA neural systems. The actions of MV-GABA were qualitatively similar to those of HOPA except for the effect on the DA neural system.     

CA125-producing adenocarcinoma of the seminal vesicle

A case of primary seminal vesicle carcinoma is reported. The tumor was a CA125-producing adenocarcinoma consisting of fine papillary-tubular, intricate branching or anastomosing glandular structures and was composed of small cuboidal, but occasionally hobnailed, cells with mostly clear, but occasionally granular, cytoplasm. Some tumor cells showed evidence of secretion of seromucinous materials into the interpapillary and cystic space. lmmunohistochemically, almost half of the tumor cells expressed a positive reaction with anti-CAl25, a common serological marker for ovarian epithelial carcinomas; however, no tumor cells expressed any other serological tumor markers such as carcinoem-bryonic antigen, α-fetoprotein, human chorionic gonadotropin, prostatic specific acid phosphatase, or prostatic specific antigen. The patient showed a high level of serological CA125, which fluctuated parallel with the growth, removal and recurrence of the tumor. The morphological and immunohistochemical findings suggested a close relationship between the present tumor and clear cell carcinoma of the ovary, which is thought to be of a Müllerian-Wolfian duct origin.     

TPA-induced cohort migration of well-differentiated human rectal adenocarcinoma cells: cells move in a RGD-dependent manner on fibronectin produced by cells, and phosphorylation of E-cadherin/catenin complex is induced independently of cell-extracellular matrix interactions

 We have already presented a two-dimensional cell motility assay using a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1 as a motility model of tumour cells of epithelial origin. In this model, L-10 cells showed locomotion as a coherent sheet when stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA), and we called this type of movement ”cohort migration”. Electron and immunoelectron microscopic study of the migrating cell sheets demonstrated localized release from cell–cell adhesion only at the lower portion of the cells with loss of E-cadherin immunoreactivity, and this change was associated with increased tyrosine phosphorylation of the E-cadherin–catenin complex, including β-catenin. Cell–extracellular matrix (ECM) interactions involved in this TPA-induced cohort migration and their effect on tyrosine phosphorylation of the E-cadherin-catenin complex have now been investigated. L-10 cell cohort migration was almost completely inhibited by addition of Arg-Gly-Asp (RGD) peptide into the medium, and thus RGD dependent. Cohort migration was stimulated on type I and IV collagens, fibronectin (FN)- and laminin-coated substratum, but was inhibited by RGD only on FN-coated surface. By using immunofluorescent techniques, FN was demonstrated preferentially around migrating cells, and a protein synthesis inhibitor, cycloheximide, inhibited the migration by about 75%. FN produced by L-10 cells were found to be mostly EDA+ FN when analysed by RT-PCR. Moreover, anti-FN antibody, but not anti-vitronectin antibody, inhibited the TPA-induced cohort migration almost completely. Thus, it was likely that L-10 cells produced FN themselves and moved on the FN substrate in an RGD-dependent manner. However, stimulation of migration by type I collagen coating and inhibition by RGD treatment did not affect the tyrosine phosphorylation of the E-cadherin–catenin complex induced by TPA, indicating that cell–cell interactions were adjusted to suit cell migration, irrespective of the condition of cell–ECM adhesion, during TPA-induced cohort migration. Received: 31 December 1997 / Accepted: 2 April 1998     

现代免疫佐剂研究

佐剂在广义上是指通过特异性或非特异性免疫增强作用提高血清中疫苗抗原特异性抗体水平的物质。可溶性纯化蛋白质疫苗或蛋白质亚单位疫苗的免疫激活作用通常较弱，不足以刺激机体产生足够的抗体，因此通常在疫苗制剂中加入佐剂。与单独应用抗原相比，抗原与佐剂联合应用所需的抗原量较少，机体产生的抗体量较多，并且还可以减轻免疫耐受。     

Diagnostic utility of galectin-3 and CD26/DPPIV as preoperative diagnostic markers for thyroid nodules

The aim of this study was to search for diagnostic markers that could correctly identify thyroid nodular lesions requiring urgent surgical treatment. We investigated whether galectin-3 and dipeptidyl peptidase IV (CD26/DPPIV) could be potential markers for improving the diagnostic accuracy of conventional cytology. Seventy-nine patients with histologically proven thyroid diseases were analyzed. The immunocytochemical staining results showed galectin-3 expression in neoplastic cells of all 37 papillary carcinomas, five of six follicular carcinomas, all three anaplastic carcinomas, one of three medullary carcinomas, and two of 14 follicular adenomas. All 16 adenomatous goiters were negative for galectin-3 immunostaining. On the other hand, all 37 papillary carcinomas, all six follicular carcinomas, and one of three anaplastic carcinomas revealed CD26/DPPIV expression, whereas all three medullary carcinomas were negative. Among benign thyroid lesions, four of 14 follicular adenomas and two of 16 adenomatous goiters exhibited varying degrees of immunoreactivity for CD26/DPPIV. RT-PCR analysis demonstrated overexpression of galectin-3 and CD26/DPPIV mRNAs in all six papillary and all three follicular carcinomas analyzed, whereas the mRNA expressions of these molecules were barely or not detectable in benign thyroid lesions and normal thyroid tissues, except for one case of follicular adenoma. In conclusion, we demonstrate that galectin-3 and CD26/DPPIV were consistently coexpressed at protein and mRNA levels in differentiated thyroid carcinomas. We propose that combined immunostaining for galectin-3 and CD26/DPPIV in the preoperative evaluation of thyroid nodules may play a role in accurate cytodiagnosis.     

Denervation of dopaminergic neurons with 6-hydroxydopamine increases nerve growth factor content in rat brain.

Denervation of dopaminergic neurons by intra nigral injection of 6-hydroxydopamine (6-OHDA) increased nerve growth factor (NGF) content in the cortex and hippocampus, both of which are innervated by cholinergic neurons. The increase continued during an observation period of 0.5-28 days after the lesion. The time course of changes in NGF content was quite different from that of cholinergic neuron denervation. The decreased dopamine content produced in the striatum by 6-OHDA injection was not recovered during the observation period. These results suggest that dopaminergic neuron damage may affect NGF synthesis.     

Fibrous dysplasia of the skull presenting interesting neuroradiological findings

A case of fibrous dysplasia of the frontal bone in a 51 year-old male is described. He was admitted to our hospital with a hard, painless growing mass in the left frontal region. A symmetrical protrusion of his forehead has been observed since several years before. Neurological examination and laboratory data revealed no abnormalities. Skull x-rays demonstrated two different lesions. One showed a ground glass appearance in the supraorbital region, and the other showed a radiolucent lesion with marginal sclerosis crossing the left coronal suture CT scan revealed an intradiploic multilocular mass. T1 and T2 MR images showed an abnormal low-intensity mass, and heterogeneous gadolinium-enhancement was noticed in both lesions. Selective external carotid angiography showed tumor stain in the left coronal mass fed by middle meningeal and superficial temporal arteries mimicking intraosseous meningioma. On the other hand, a supraorbital hyperostotic lesion showed no apparent vascularity. An operation was performed on the left coronal lesion to verify the nature of the progressively enlarging mass, which was histologically confirmed to be a fibrous dysplasia rich in numerous vessels. Postoperative course was uneventful. Correlation with clinical activity and enhancement pattern was not known, however, careful observation is required in hypervascular fibrous dysplasia such as was observed in this case.