Purinergic P2X receptor activation induces emetic responses in ferrets and Suncus murinus (house musk shrews).

BACKGROUND AND PURPOSE: Despite the rapid progress made in understanding the significant role played by signalling via extracellular ATP in physiology and pathology, there has been no clear information generated on its involvement in the emetic response. EXPERIMENTAL APPROACH: In the present study, the emetogenic potential of extracellular ATP signalling in mammalian species was examined using ferrets and Suncus murinus (house musk shrews). A slowly degradable ATP analogue, alpha,beta-methyleneATP (alpha,beta-meATP), was used to activate the P2X receptors, and either the non-selective P2 receptor antagonist, pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), or the specific P2X(3) homomer and P2X(2/3) heteromer antagonist, A-317491, were tested against the agonist-induced response. KEY RESULTS: Intraperitoneal injection of alpha,beta-meATP produced significant emetic responses in ferrets (1 - 30 mg kg(-1)) and in Suncus murinus (5 - 50 mg kg(-1)). The responses occurred frequently within the first 10 min after administration, much less frequently from 11 to 60 min and no responses occurred later than 60 min. The emetic responses were completely inhibited by intraperitoneal pre-treatment with PPADS (100 mg kg(-1)) or A-317491 (100 mg kg(-1)). Abdominal surgical vagotomy did not reduce the emetic response in Suncus murinus significantly. CONCLUSIONS AND IMPLICATIONS: These results for the first time indicate that the activation of P2X receptors evokes emetic responses in mammalian species. The P2X(3) homomer and.or P2X(2/3) heteromer in the area postrema could be responsible for the emetic response. This finding contributes to the elucidation of the roles played by extracellular ATP signalling in various emetic symptoms.

[Mediastinal lymph-node carcinoma with no apparent primary lesion; report of a case].

A 57-year-old woman was admitted to our department because of a chest X-ray showing a mass shadow about 40 mm in diameter in the right side of the middle of the mediastinum. A chest computed tomography(CT) scan demonstrated a large tumor, adherent to the superior vena cava and right pulmonary artery. No other metastases and no primary tumor were found. The tumor was resected through median sternotomy. Intraoperative frozen section analysis showed that the mediastinal tumor was a metastatic lymph-node carcinoma. Postoperative examination, too, did not detect the primary lesion. Radiotherapy was given after the operation. This case was thought to be a very rare case of T0N2M0 lung cancer or primary mediastinal lymph-node carcinoma (yolk sac tumor).

[Lateral femoral circumflex artery as a free graft for coronary artery bypass grafting to an 85-year-old man; report of a case].

An 85-year-old man had a 2 vessel coronary disease. Preoperative echogram showed the lateral femoral circumflex artery (LFCA) had enough diameter and length. We performed coronary artery bypass grafting (OPCAB) with the left internal thoracic artery (LITA) and LFCA. Postoperative coronary angiogram showed that the LFCA bypass graft was patent and supplied sufficient blood to the anastomosed vessel.

Brainstem auditory regions in mice: expression of nociceptin/orphanin FQ precursor mRNA in select neurons.

Nociceptin peptide-receptor system is known to be essential for the regulation of hearing ability. The mRNA for nociceptin precursor protein is highly expressed in the brainstem. We explored a detailed hybridohistochemical expression pattern of the nociceptin precursor mRNA in the mouse brainstem, and identified positive cells in several auditory brainstem nuclei. Positive cells were seen in the dorsal and ventral nuclei of the lateral lemniscus, the rostral periolivary region, the lateroventral and medioventral periolivary nuclei, the dorsal periolivary region, the superior paraolivary nucleus, and the external cortex and dorsal cortex of the inferior colliculus. Of these, the medioventral and lateroventral periolivary nuclei, the major sites of origin of olivocochlear bundle, were most populated by positive cells.

Gene mutation in hereditary progressive dystonia with marked diurnal fluctuation (HPD), strictly defined dopa-responsive dystonia.

Mutations of the guanosine triphosphate (GTP)-cyclohydrolase I (GCH-I) gene, which catalyzes the first step in the tetrahydrobiopterin (the natural cofactor for tyrosine hydroxylase) biosynthesis, are demonstrated to cause HPD, i.e. strictly defined dopa-responsive dystonia. We analyzed the GCH-I gene of patients who fulfilled clinical criteria for typical hereditary progressive dystonia (HPD) to finalize the diagnosis. Two novel point mutations in two independent families and one novel de novo point mutation in one sporadic patient were identified. In a Japanese family, a T-to-C transition was found at exon 2, which resulted in a substitution of Cys 141 to Arg. In another Japanese family, a C-to-T mutation in exon 4 caused a nonsense codon Gln180Stop. In a clinically sporadic Japanese patient, T-to-G transition in exon 1 brought Met 102 Arg missense mutation, which was not observed in its biological parents. These three mutations were not observed in previously reported 57 pedigrees/patients and no polymorphisms in the coding region of the GCH-I gene were identified. None of the mutations of GCH-I gene in HPD reported to date or in this study have been detected more than once in any ethnicity suggesting a relatively high spontaneous mutation rate in this gene.

Distribution of nociceptin/orphanin FQ precursor protein and receptor in brain and spinal cord: a study using in situ hybridization and X-gal histochemistry in receptor-deficient mice.

Nociceptin/orphanin FQ (N/OFQ) is an opioid-like heptadecapeptide agonist for the opioid receptor homolog, N/OFQ receptor. To explore the precise distribution of the peptide-receptor system, the authors examined the brain and spinal cord from receptor-deficient mice bearing the targeted mutation (morc(m1)), a lacZ insertional mutation in the N/OFQ receptor gene. Precursor protein N/OFQ (preproN/OFQ) mRNA was detected by using in situ hybridization, and the N/OFQ receptor was detected by using X-gal histochemistry. The N/OFQ receptor reflected by lacZ expression was observed at high levels in the dentate gyrus, lateral septum, subparafascicular thalamic nucleus, medial preoptic area, median preoptic nucleus, ventromedial preoptic nucleus, anterior hypothalamic area, paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, auditory brainstem nuclei, pontine dorsal tegmentum, and nucleus of the solitary tract. In situ detection of the N/OFQ receptor mRNA by digoxigenin-labeled riboprobes coupled with tyramide signal amplification in normal and wild-type mice resulted in the regional distribution paralleling the lacZ expression in these regions. PreproN/OFQ mRNA was expressed at high levels in the subparafascicular thalamic nucleus, central gray, central tegmental field, auditory brainstem nuclei, caudal spinal trigeminal nucleus, and spinal dorsal horn. Furthermore, variable levels of expression of the peptide and receptor were seen in distinct sites of the brain and spinal cord. These data indicate a correspondence of the peptide and the receptor in local distribution at limbic, hypothalamic, and brainstem sites. Together with concurrent physiologic and behavioral studies in mutant mice, the results suggest functional roles for the N/OFQ system, including the central regulation of learning and memory, hearing ability, water balance, food intake, and blood pressure.

Comparative distribution of GABAergic and peptide-containing neurons in the lateral lemniscal nuclei of the rat.

By immunostaining, neurons expressing peptides (dynorphin and corticotropin-releasing factor, CRF) and glutamate decarboxylase (GAD), a GABA-synthesizing enzyme, were precisely mapped in the rat lateral lemniscal nuclei. While GAD neurons were numerous and preferably localized in the dorsal (DLL) and ventral (VLL) nuclei, neurons expressing these peptides were less numerous and localized primarily in the intermediate (ILL) nucleus of the lateral lemniscus. The ILL nucleus was shown to project to the inferior colliculus and to express Fos rapidly in response to peripheral acoustic stimulation, suggesting that the ILL nucleus may take part in non-GABAergic relay of acoustic information in the lateral lemniscus.

[Evaluation of frozen section diagnosis of parotid gland tumors].

A retrospective study is presented comparing the results of 167 frozen section diagnoses of surgical extirpated parotid gland tumors with permanent-section diagnoses. Percentages of correct diagnosis for malignancy (cases correctly classified as benign or malignant tumors) and of correct diagnosis for histopathology (cases in which frozen section diagnosis and permanent-section diagnosis were identical) were calculated. Percentages of correct diagnosis for malignancy in all cases, benign cases, and malignant cases were 98.8%, 99.3%, and 95.8%, respectively. Percentages of correct diagnosis for histopathology in all cases, benign cases, and malignant cases were 94.0%, 97.2%, and 75.0%, respectively. These results are superior to the previous reports both of frozen section diagnosis and of fine-needle aspiration biopsy diagnosis although the data for histopathological diagnosis in malignant tumors are average compared to previous reports. We conclude that diagnoses of most parotid gland tumors based on frozen section examination are reliable and accurate, but caution should be exercised in malignant tumors diagnosis.

[Clinical study of parotid tumors: a 20 year statistical analysis of 633 cases].

During the 20 years from 1977 to 1996, 633 cases underwent excisions of parotid tumors (539 benign and 94 malignant) in the department of Otolaryngology of Kansai Medical University. The incidence of Warthin's tumors in the years from (1987 to 1996) was higher than that in the years from 1977 to 1986. On the other hand, the incidence of mucoepidermoid carcinomas was less than in previous reports. Tumors accompanied with spontaneous pain or facial nerve palsy and with invasion to both lobes frequently indicated malignancy. Facial nerve palsy caused by either benign or malignant tumors before operation showed no improvement after surgery. The incidences of facial nerve palsy (1.0% in benign, and 18.3% in malignant) and Frey's syndrome (17.8% in benign, and 18.3% in malignant) after surgery were lower than those in other reports of both benign and malignant tumors. Five-year mortality was 76.1%. All deaths that occurred five years after operation involved highly grade malignant tumors.

Distribution of neurons expressing alpha 1G subunit mRNA of T-type voltage-dependent calcium channel in adult rat central nervous system.

T-type voltage-dependent calcium channel has central roles in neuronal burst firing. The alpha1G subunit of T-type channel has been recently cloned and we here reported a cellular distribution of the alpha1G by in situ hybridization in adult rat brain and spinal cord. The cells expressing alpha1G were widely distributed in the central nervous system. The distribution seemed to be restricted to neurons, and exhibited a specific pattern in the cerebellum, thalamus, hippocampus and cerebral cortex.

[A case report of vein graft rupture (post-CABG) by poststernotomy mediastinitis].

Mediastinitis after cardiac surgery is a serious complication with high mortality rates. A 66-year-old woman undergoing CABG developed mediastinitis due to MRSA. The infection was treated by radical debridement and continuous mediastinal irrigation. At the 9th day of irrigation, vein graft rupture with massive bleeding was suddenly occurred and instantly surgical repair (suture of ruptured vein graft) and omental transposition were done. We conclude that omental flap transposition is effective in the management of mediastinitis after cardiac surgery.

Antibiotic-induced endotoxemia in a patient with endogenous endophthalmitis.

PURPOSE: The aim of the study is to describe a case of suspected endotoxin-induced uveitis associated with septic endogenous endophthalmitis followed by antibiotic-induced endotoxemia. METHODS: The human leukocyte antigen (HLA) typing of peripheral leukocytes was studied by lymphocytotoxicity technique. Histological and immunohistochemical studies of paraffin embedded specimen were conducted. RESULTS: Findings of HLA typing revealed positive reaction for B 51, Cw 3, DR 8, DR 11, DQ 3. The vitreous body of an eviscerated eye was occupied by the non-specific granulomatous tissue, composed of fibroblast, plasma cells, and Sudan black staining positive foamy cells, including melaniferous phagocytes, identified as CD 68 positive macrophage. CONCLUSION: It is suggested that antibiotic-induced endotoxemia of a patient with septic endogenous endophthalmitis produced endotoxin-induced uveitis under an upregulation of HLA and endotoxin activated macrophages may release cytokines, followed by fibrin formation and subsequent granuloma.

Multiresidue analysis of pesticides in vegetables and fruits using a high capacity absorbent polymer for water.

A single extraction and a single clean-up procedure was developed for multi-residue analysis of pesticides in non-fatty vegetables and fruits. The method involves the use of a high capacity absorbent polymer for water as a drying agent in extraction from wet food samples and of a graphitized carbon column for clean-up. A homogeneously chopped food sample (20 g) and polymer (3 g) were mixed to absorb water from the sample and then 10 min later the mixture was vigorously extracted with ethyl acetate (100 ml). The extract (50 ml), separated by filtration, was loaded on a graphitized carbon column without concentration. Additional ethyl acetate (50 ml) was also eluted and both eluates were concentrated to 5 ml for analysis. The procedure for sample preparation was completed within 2 h. In a recovery test, 107 pesticides were spiked and average recoveries were more than 80% from asparagus, orange, potato and strawberry. Most pesticides were recovered in the range 70-120% with usually less than a 10% RSD for six experiments. The results indicated that a single extraction with ethyl acetate in the presence of polymer can be applied to the monitoring of pesticide residues in foods.

[A case of racemose hemangioma of the right bronchial artery and intercostal to pulmonary arterial anastomosis].

We reported a case of racemose hemangioma of the bronchial artery and intercostal to pulmonary arterial anastomosis. A 67-year-old woman was admitted because of repeated hemoptysis. Bronchoscopic examination revealed a torous lesion of the right B7 bronchus. Intercostal angiography demonstrated communications between right dilated, meandered intercostal arteries and right pulmonary artery. Bronchial angiography showed dilatation and convolution of the right bronchial artery. Angiographic embolization of the right bronchial artery and the right intercostal artery was underwent. There was no recurrence of hemoptysis one year after the embolization procedure. We think that angiographic embolization is an effective method of treatment of hemoptysis due to racemose hemangioma of the bronchial artery and intercostal to pulmonary arterial anastomosis.

[An operative case of congenital fistula of the right coronary artery to the left ventricle with congestive heart failure].

We reported an extremely rare case of congenital fistula of the right coronary artery to the left ventricle in a 71-year-old man who suffered from difficulty in breathing and palpitation. The diagnosis was confirmed by the right coronary angiography. The fistula was closed by Symbas's operation under cardiopulmonary bypass. Postoperative recovery was uneventful. Coronary angiography performed one year after the operation revealed that the right coronary artery was completely occluded by thrombus. But there were no signs of myocardial ischemia or infarction. And so we suspected that the dilated right coronary artery had not work as functional vessel.

Antiemetic effects of morphine on motion- and drug-induced emesis in Suncus murinus.

Emetic and antiemetic effects of morphine were investigated in Suncus murinus. Subcutaneous (up to 30 mg/kg) or intracerebroventricular administration (50 micrograms) of morphine failed to cause emesis. However, pretreatment with morphine (s.c.) prevented the emesis induced by nicotine (10 mg/kg, i.p.), copper sulfate (40 mg/kg, p.o.), cisplatin (20 mg/kg, i.p.) and motion stimulus. These results suggest that morphine has only antiemetic potency and may block a common mechanism for the emetic reflex of suncus, because the antiemetic effects of the drug were exerted irrespective of the stimulus.