Localization and developmental expression of a novel protein kinase C delta gene.

The expression and localization of a novel protein kinase C delta (nPKC delta) mRNA were investigated using Northern blotting and in situ hybridization in the developmental process of mouse brain. In adult mice, nPKC delta was abundantly expressed in the thalamus, moderately in the pons and the cerebellum, but faintly in the cerebral cortex and the spinal cord. By in situ hybridization, the signals were observed specifically at the sensory and motor relay nuclei of the thalamus, the dorsal cochlear nuclei of the pons, and the molecular layer of the cerebellum. When developmental changes in the expression of nPKC delta gene were analyzed by in situ hybridization, it was not detectable in embryonic and neonatal brains, very weakly expressed in the thalamus in the first week, and highly expressed at two weeks of age. These results suggest that the gene expression of nPKC delta is strictly controlled by both the cell type and the developmental process.     

The tumor promoters 12-O-tetradecanoylphorbol-13-acetate and okadaic acid differ in toxicity, mitogenic activity and induction of gene expression

Okadaic acid (OA) and 12-O-tetradecanoylphorbol-13-acetate (TPA)are both potent tumor promoters in a mouse skin carcinogenesisexperiment. OA was much more toxic than TPA for murine embryocell lines such as Swiss 3T3 cells or C3H10T? cells. TPA isa potent mitogen for 3T3 cells; in contrast OA was unable tostimulate DNA synthesis in these cells. TPA induces a familyof primary response genes, the TPA induced sequence (TIS) genes,in a wide variety of cells. Although OA induced modest levelsof TIS mRNA expression, the time course of the induction ofTIS1 and TIS8 mRNA was delayed when compared to induction byTPA or peptide mitogeas such as fibroblast growth factor (FGF).In addition TPA-mediated down-regulation of protein kinase Cattenuated TIS gene induction by OA, but not by FGF.     

Diuretic and hypotensive actions of torasemide in hypertensive models of rat

The diuretic and the antihypertensive actions of torasemide were examined in renal and genetic hypertensive rats and compared to the effects of furosemide. Oral administration of torasemide (1 and 3 mg/kg) elicited a dose-dependent increase in the excretion of urine and electrolytes and elevated the urinary Na/K ratio in both renal and genetic hypertensive rats. Torasemide and furosemide had a similar maximum diuretic effect in the normotensive Wistar rat and the spontaneously hypertensive rat (SHR). However, the diuretic activity of furosemide was weaker in the renal hypertensive rat (RHR). Torasemide showed approximately 30 times greater diuretic potency than furosemide. Torasemide and furosemide demonstrated hypotensive action in hypertensive rat models, but not in the normotensive Wistar rat. Especially in the RHR, torasemide exhibited a more potent hypotensive action than furosemide. These results show that the diuretic and antihypertensive activities of torasemide are effective in various rat models of hypertension, while the diuretic activity of furosemide is weak in certain hypertensive rat models. © 1992 Wiley-Liss, Inc.     

LAPAROSCOPIC TREATMENT FOR PERFORATED APPENDICITIS WITH PELVIC ABSCESS

We performed laparoscopic appendectomy and drainage to treat panperitonitis due to perforated appendicitis that occurred in a 28‐year‐old woman. We believe this is an appropriate procedure to treat perforated appendicitis because it is safe and minimally invasive, and faster recovery can be expected than after conventional open appendectomy.     

Primary pulmonary valve papillary fibroelastoma

Papillary fibroelastoma (PFE) is a rare and benign cardiac tumor typically found on the valvular endocardium. In most cases, PFE is identified incidentally on echocardiography or during cardiac surgery. The patient was a 73-year-old man who had been treated for hepatocellular carcinoma for 5 years. On echocardiography, a 2.5-cm diameter mass was detected in the pulmonary trunk just above the pulmonary valve. Through a transpulmonary arterial approach with cardiopulmonary bypass, the mass identified on the commissure of the right and posterior pulmonary cusp was surgically excised together with the attached endocardium. Despite the benign histology of PFE, lethal embolic events such as stroke, myocardial infarction, and pulmonary embolism are reported in some cases. To prevent such complications, tumor identification and surgical excision are essential.     

Covalent binding of rofecoxib, but not other cyclooxygenase-2 inhibitors, to allysine aldehyde in elastin of human aorta.

In rats, it has been reported that rofecoxib, a cyclooxygenase-2 (COX-2) inhibitor, reacts with the aldehyde group of allysine in elastin to give a condensation covalent adduct, thereby preventing the formation of cross-linkages in the elastin and causing degradation of the elastic fibers in aortas in vivo. Acid, organic solvent, and proteolytic enzyme treatments of human aortic homogenate after incubation with [(14)C]rofecoxib demonstrated that most of the radioactivity is covalently bound to elastin. The in vitro covalent binding was inhibited in the presence of beta-aminopropionitrile, D-penicillamine, and hydralazine, which suggested that the aldehyde group of allysine in human elastin was relevant to the covalent binding. The in vitro covalent binding of [(14)C]rofecoxib was significantly decreased by the addition of only nonradiolabeled rofecoxib but not the other COX-2 inhibitors, celecoxib, valdecoxib, etoricoxib, and CS-706 [2-(4-ethoxyphenyl)-4-methyl 1-(4-sulfamoylphenyl)-1H-pyrrole], a novel selective COX-2 inhibitor. All the above COX-2 inhibitors except for rofecoxib had no reactivity with the aldehyde group of benzaldehyde used as a model compound of allysine aldehyde under a physiological pH condition. On the other hand, no retention of the radioactivity of [(14)C]rofecoxib was observed in human aortic endothelial cells in vitro, suggesting that rofecoxib is not retained in aortic endothelial cells in vivo. These results suggest that rofecoxib, but not other COX-2 inhibitors, is capable of covalently binding to the aldehyde group of allysine in human elastin. This might be one of the main causes of cardiovascular events by rofecoxib in clinical situations.     

Evaluation of the Japanese-Chinese Herbal Medicine,Kampo, for the Treatment of Lupus Dermatoses in Autoimmune Prone MRL/Mp-lpr/lpr Mice

Kampo, a Japanese-Chinese traditional herbal medicine, has been used for the treatment of various diseases for about 3,000 years in China. Among herbal medicines, Sairei-to is well known for improving the symptoms of rheumatoid arthritis (RA) and other collagen diseases. However, its immunosuppressive effects on autoimmune cutaneous phenomena are not completely understood. We investigated the effects of Sairei-to on the development of lupus dermatoses in autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mice, an animal model which spontaneously develops skin lesions similar to those seen in human lupus erythematosus. Virgin female MRL/lpr mice at 1 month of age, which were treated orally with Sairei-to, had reduced amounts of IgG deposition at the dermoepidermal junction, titers of anti-DNA antibodies and rheumatoid factor, and lymphoproliferation. These results support the use of traditional herbal medicines in patients with human RA and systemic lupus erythematosus.     

Case of Parkinson's disease presenting with unique dyspneic attacks caused by oromandibular dystonia and sleep apnea syndrome]

A 79-year-old woman with a 4-year history of Parkinson's disease was admitted due to unique dyspneic attacks with cyanosis while eating. Dyspneic attacks with cyanosis occurred mainly during actions such as taking meals or rehabilitation. Due to increased tonus of the orbicularis oris muscle, she was unable to open her mouth and breathe out, and finally experienced hypoxemia as revealed by pulse oxymetry. Dystonic hypertonus was relieved by touching the mandible with the fingers, and she was able to open her mouth again. These symptom was compatible with the sensory trick. Based on these findings, we considered that dyspneic attacks were produced by focal oromandibular dystonia. Polysomnography also showed central sleep apnea. We report herein a rare case of Parkinson's disease presenting with respiratory insufficiency caused by focal dystonia and central sleep apnea.     

Heterotopic ischemic pain attenuates somatosensory evoked potentials induced by electrical tooth stimulation: diffuse noxious inhibitory controls in the trigeminal nerve territory.

The purpose of this study was to determine whether the late component of somatosensory evoked potentials (SEP) induced by electrical tooth stimulation and pain intensity are inhibited by heterotopic ischemic stimulation. The tourniquet pressure with 50 mmHg greater than the individual's systolic pressure was applied to the left upper arm for 10 min as ischemic conditioning stimulation. The late component of SEP and visual analogue scale (VAS) were recorded at 4 times and both were significantly decreased when ischemic conditioning stimulation was applied. The maximum reductions in SEP amplitude and the VAS value were 26.1% and 21.2%, respectively, during ischemic conditioning stimulation. After-effect was observed 5 min after removal of the conditioning stimulation. The present study revealed that heterotopic ischemic stimulation attenuated the late component of SEP induced by electrical tooth stimulation, triggering diffuse noxious inhibitory controls (DNIC) and after-effects in the trigeminal nerve territory. It was also suggested that the DNIC effect differs, depending on the intensity, kind, and quality of the test and conditioning stimuli.