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.

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.

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.

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.

[Mechanism of cisplatin and peplomycin therapy on head and neck carcinoma].

Results of chemotherapy for head and neck cancer are now improving owing to the development of concomitant use of chemotherapeutic agents such as cisplatin or peplomycin. Concomitant use of the two agents has been favored clinically. However, fundamental study on the combination therapy has not been carried out sufficiently. In the present study we studied the cell kinetics of tumor cells by the combination of cisplatin and peplomycin using flowcytometric analysis and electron microscopy. Survival of tumor cells was lowest, when peplomycin was administrated 3 days after cisplatin. Cell kinetics showed an accumulation at the S and G2M stage in this situation, By the electron microscopic study, microvilli of tumor cells disappeared and the blebbing of tumor cells was observed, when cisplatin alone was administrated. However, when the combination of cisplatin and peplomycin was administrated to the tumor cells, tumor cells enlarged. The results suggest that the mechanism of combination therapy differed from the mechanism of cisplatin alone.

[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.

[Female urethral diverticulum calculi: a case report].

A case of urethral diverticulum with calculus in a 53-year-old woman is reported. She was admitted to Isahaya General Hospital complaining of a localized swelling in the external genitalia. We found a urethral diverticular calculi by urethrography. Urethral diverticulectomy was carried out without any complications. The removed stones were in 2 pieces and they were composed of calcium phosphate and ammonium urate.

Non-hormonal adrenocortical adenoma with oncocytoma-like appearances.

We report a case of non-hormonal adrenocortical adenoma. The tumor was removed en block with the adrenal gland. The specimen was 5.0 X 4.5 X 3.0 cm, weighed 30 g and was solid. Histologically, this tumor had an oncocytoma-like appearance. However, as there is no concept of oncocytoma in connection with adrenocortical adenoma, this case was diagnosed as adrenocortical adenoma. A case with such histological findings has never been reported.

[Partial cystectomy for bladder carcinoma: lyophilized human dura as a bladder wall substitute].

Ten cases were treated by partial cystectomy for bladder carcinoma (anterior wall 5 cases, dome 1 case, dome to anterior wall 2 cases, lateral wall 2 cases) and these defects were covered with lyophilized human dura (LHD). A few minutes before use, LHD was put into saline for rehydration and, for anastomosis, we used 2 zero plain catgut. In eight cases cardiovascular complications, DM and liver cirrhosis were found before operation. The mean operation time +/- SD was 109 +/- 26 minutes, and the indwelling catheter was left in place for 15 to 42 days. In three cases, prolonged urine leak from the wound continued after operation, and in one case temporal VUR was found without clinical significance. No severe urinary tract infection was found in all cases. The inner surface of dura was almost epithelialized after 8 weeks, 8 cases were in good clinical condition but one case was treated by TUR for recurrence of bladder tumor 1 year and 3 months after operation. Our results with LHD as a substitute for the bladder wall have been satisfactory. The main advantage of this technique is that large vesical segmental resection is possible to such an extent as to satisfy Prout's criteria (at least 3 cm of apparently normal bladder are available to be excised around the tumor).

[Successful treatment by using a pedicled omental flap for sternal osteomyelitis and mediastinal infection caused by MRSA].

A 56-year-old male case, who was complicated with sternal osteomyelitis and mediastinitis after aortic valve replacement, was reported. Its infection was caused by MRSA (methicillin resistant Staphylococcus aureus). He was treated with sterilization of wound using povidone iodine, Minomycin solution and its injection for 10 days. And thereafter we decided to apply the plastic surgical technique to this case. After debridement of the infected granulation and sternum thoroughly, a pedicled omental flap was transposed successfully.

[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.

[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).

[A case of thymic carcinoma, sarcomatoid type].

A 53-year-old man was found to have a mediastinal mass. Chest X-ray, CT scan, bronchofiber and superior vena vasography showed a left upper giant mediastinal tumor with invasion to left upper lobe and pericardium. And it was performed a surgical treatment and diagnosed a thymic carcinoma (sarcomatoid type) by histological examination. We reported a rare type of thymic carcinoma and added discussion.

[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.