The lack of a clonal renin-secreting cell line has greatly hindered the investigation of the regulatory mechanisms of renin secretion at the cellular, biochemical, and molecular levels. In the present study, we investigated whether it was possible to induce phenotypic switching of the renin-expressing clonal cell line As4.1 from constitutive inactive renin secretion to regulated active renin secretion. When grown to postconfluence for at least two days in media containing fetal bovine serum or insulin-like growth factor-1, the formation of cell-cell contacts via N-cadherin triggered downstream cellular signaling cascades and activated smooth muscle-specific genes, culminating in phenotypic switching to a regulated active renin secretion phenotype, including responding to the key stimuli of active renin secretion. With the use of phenotype-switched As4.1 cells, we provide the first evidence that active renin secretion via exocytosis is regulated by phosphorylation/dephosphorylation of the 20 kDa myosin light chain. The molecular mechanism of phenotypic switching in As4.1 cells described here could serve as a working model for full phenotypic modulation of other secretory cell lines with incomplete phenotypes.

Recent studies have documented that Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathway can modulate the apoptotic program in a myocardial ischemia/reperfusion (I/R) model. To date, however, limited studies have examined the role of JAK3 on myocardial I/R injury. Here, we investigated the potential effects of pharmacological JAK3 inhibition with JANEX-1 in a myocardial I/R model. Mice were subjected to 45 min of ischemia followed by varying periods of reperfusion. JANEX-1 was injected 1 h before ischemia by intraperitoneal injection. Treatment with JANEX-1 significantly decreased plasma creatine kinase and lactate dehydrogenase activities, reduced infarct size, reversed I/R-induced functional deterioration of the myocardium and reduced myocardial apoptosis. Histological analysis revealed an increase in neutrophil and macrophage infiltration within the infarcted area, which was markedly reduced by JANEX-1 treatment. In parallel, in in vitro studies where neutrophils and macrophages were treated with JANEX-1 or isolated from JAK3 knockout mice, there was an impairment in the migration potential toward interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), respectively. Of note, however, JANEX-1 did not affect the expression of IL-8 and MCP-1 in the myocardium. The pharmacological inhibition of JAK3 might represent an effective approach to reduce inflammation-mediated apoptotic damage initiated by myocardial I/R injury.
Animals ; Apoptosis/drug effects ; Cell Movement/drug effects ; Chemokines/pharmacology ; Heart Function Tests/drug effects ; Inflammation/pathology ; Janus Kinase 3/*antagonists & inhibitors/metabolism ; Macrophages/drug effects/metabolism/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Myocardial Reperfusion Injury/drug therapy/*enzymology/physiopathology/*prevention & control ; Myocardium/enzymology/pathology ; Myocytes, Cardiac/drug effects/metabolism/pathology ; Neutrophils/drug effects/metabolism/pathology ; Quinazolines/pharmacology/therapeutic use

Gap junction protein, connexin, is expressed in endothelial cells of vessels, glomerulus, and renin secreting cells of the kidney. The purpose of this study was to investigate the role of gap junction in renin secretion and its underlying mechanisms using As 4.1 cell line, a renin-expressing clonal cell line. Renin release was increased proportionately to incubation time. The specific gap junction inhibitor, 18-beta glycyrrhetinic acid (GA) increased renin release in dose-dependent and time- dependent manners. Heptanol and octanol, gap junction blockers, also increased renin release, which were less potent than GA. GA-stimulated renin release was attenuated by pretreatment of the cells with amiloride, nifedipine, ryanodine, and thapsigargin. GA dose-dependently increased intracellular Ca2+ concentration, which was attenuated by nifedipine, nimodipine, ryanodine, and thapsigargin. However, RP-cAMP, chelerythrine, tyrphostin A23, or phenylarsine oxide did not induced any significant change in GA-stimulated increase of intracellular Ca2+ concentration. These results suggest that gap junction plays an important role on the regulation of renin release and intracellular Ca2+ concentration in As 4.1 cells.
Amiloride ; Calcium* ; Cell Line* ; Connexins ; Endothelial Cells ; Gap Junctions* ; Glycyrrhetinic Acid ; Heptanol ; Kidney ; Nifedipine ; Nimodipine ; Renin* ; Ryanodine ; Thapsigargin

One case of ovarian pregnancy. Ovarian Pregnacy is a rare form of ectopic pregnancy. Its estimated overall incidence is highly variable. Ovarian pregnancy occurs in the corpus luteum mostly, and is usually accompanied with the rupture of the ovary and massive hemoperitoneum. It presents as a hemorrhagic ovary and frequently misdiagnosed as a ruptured corpus luteum. Risk factors to ovarian pregnancy include a history of pelvic inflammatory disease (PID), prior pelvic surgery, use of an intrauterine contraceptive device (IUD) and ovulation induction. We have experienced one case of ovarian pregnancy and reviewed it briefly.
Corpus Luteum ; Female ; Hemoperitoneum ; Incidence ; Intrauterine Devices ; Ovary ; Ovulation Induction ; Pelvic Inflammatory Disease ; Pregnancy ; Pregnancy, Ectopic* ; Risk Factors ; Rupture

"Capsaicin, the pungent principle of hot peppers, is a neurotoxin that depletes primary sensory neurons of neuropeptides like tachykinin. The objectives of these experiment was to examine the effects of capsaicin on Salmonel/a typhimurium-induced production of cytokines such as TNF-a, IL-1B, IL-6, IL-10 and IL-12 and on production of nitric oxide in peritoneal macrophages. In addition, the effects of capsaicin on survival rates of S. typhimurium-infected mice and on nuclear transcription factor (NF-kB) activation were also investigated. Mice were pretreated with a single s.c. injection of 100 ug of capsaicin and were infected i.v. with S. typhimurium (5xO5/mouse) in 0.2 ml volume after capsaicin pretreatment. The serum cytokine levels were measured 30, 60, 120, 180 and 240 min after Salmonella infection, using ELISA kits. The activation of NF-B was also examined by gel shift assay in spleens, thymuses and brains of mice that had been pretreated with a single s.c. injection of 100 ug of capsaicin. It was found that Sa/mone/la infection induced the production of TNF-a, IL-1B, IL-6, IL-10 and IL-12, but capsaicin pretreatment inhibited the production of TNF-a, IL-1B, IL-10 and IL-12, but enhanced IL-6 production 120 min after Salmonella infection. Interestingly, the capsaicin pretreatment inhibited the activation of NF-kB in spleens and thymuses. There were no differences in the numbers of bacteria in livers, brains, spleens, kidneys and lungs between capsaicin- pretreated mice and the control animals in applied experimental conditions. Suprisingly, however, capsaicin pretreatment increased both the survival rates of Sa/mone//a-infected mice and production of nitric oxide by peritoneal macrophages compared with capsaicin-untreated control mice. Taken together, these results indicate that the capsaicin-sensitive primary sensory neurons may play an important modulatory role in the production of cytokine, nitric oxide and NF-B activation and the pathogenesis of salmonellosis."
Animals ; Bacteria ; Brain ; Capsaicin* ; Cytokines* ; Enzyme-Linked Immunosorbent Assay ; Interleukin-10 ; Interleukin-12 ; Interleukin-6 ; Kidney ; Liver ; Lung ; Macrophages, Peritoneal ; Mice ; Neuropeptides ; NF-kappa B* ; Nitric Oxide* ; Salmonella Infections* ; Salmonella typhimurium ; Salmonella* ; Sensory Receptor Cells ; Spleen ; Survival Rate ; Tachykinins ; Thymus Gland ; Transcription Factors

It is well known that tumor necrosis factor (TNF-a), interleukin-1, platelet-activating factor (PAF) and arachidonic acid metabolites, such as thromboxane and leukotriens, are major mediators involved in the pathogenesis of endotoxic shock. In this study, we have investigated the effect of pentoxifylline (inhibitor of TNF-a release), BN50739 (PAF antagonist), indomethacin (cyclooxygenase inhibitor) and diethylcarbamazine (lipoxygenase inhibitor) on LPS- induced lethality as well as the relationship between major mediators in endotoxic shock. All inhibitors described above except diethylcarbamazine significantly protected mice against LPS- induced lethality. BN50739 and indomethacin were also effective in protection of TNF-a-induced lethality. The elevation of circulating TNF-a by LPS was significantly blocked by BN50739, but not affected by indomethacin. Convulsion appeared shortly after LPS injection was prevented by BN50739 but not by indomethacin, whereas diarrhea and limited movement was prevented by indomethacin but not by BN50739. These results indicate that i) TNF-a, PAF and cyclooxygenase products are important mediators involved in the pathogenesis of septic shock and ii) TNF-a directly influenced the release or production of PAF as well as cyclooxygenase products, and strongly suggest that i) TNF-a and PAF stimulate the release of each other via positive feedback network but TNF-a and cyclooxygenase products do not form the network and ii) PAF and cyclooxygenase product appear not to affect the release of each other.
Animals ; Arachidonic Acid ; Diarrhea ; Diethylcarbamazine ; Gene Expression* ; Indomethacin ; Interleukin-1 ; Mice ; Pentoxifylline ; Prostaglandin-Endoperoxide Synthases ; Seizures ; Shock, Septic ; Tumor Necrosis Factor-alpha*

No abstract available.
Angiotensin I ; Angiotensin II* ; Angiotensins* ; Autoradiography ; Receptors, Angiotensin* ; Renin* ; Renin-Angiotensin System*

No abstract available.
Angiotensin I ; Angiotensin II* ; Angiotensins* ; Autoradiography ; Receptors, Angiotensin* ; Renin* ; Renin-Angiotensin System*

Paget bone disease(PBD) is usually focal, but can be wide spread disorder of the skeletal remodeling characterized by greatly increased osteoclast size and activity. It has extremely variable prevalence worldwide, being common in England and northern European countries and areas populated by their descendants, but strikingly uncommon in Asia, the middle east, Africa and Scandinavia. It's occurrence also shows familial clustering, some postulates autosomal dominant inheritance. Many studies have shown that paramyxoviruses may play a critical role in the etiology of this disorder. However, the precise etiology of PBD remains unknown.We describe a kindred with PBD in 3 successive generations. The propositus, a 55-year-old man, has panostotic PBD and giant cell reparative granuloma of pagets disease involving his head, mandible, abdomen and ileum, rare tumorous complication of Paget's disease. Bowed limbs were first noticed at age 25 years, and progressed for 20 years. Giant cell reparative granuloma began manifesting at age 45 years, and responded dramatically to high-dose dexamethasone therapy. His pretreatment biochemical finding were remarkable for elevated serum ALP, 765(normal 66-220 u/L) and osteocalcin, 154(normal 6.3-30.7 mg/ml), but normal serum calcium, phosphorous, 250HD and PTH. A nondecalcified iliac crest specimen demonstrated classic histopathologic 25OHD and PTH. A nondecalcified iliac crest specimen demonstrated classic histopathologic changes of PBD on light microscopy. His decreased father had a similar degree of bony deformities beginning at age 20 years, but had not been examined. His two asymptomatic daughters, 20 and 24-year-old, were both found to be affected with widespread PBD by bone scan, radiographic study, and their serum ALP levels, 939 and 435U/L, respectively. This is the first report of familial occurance of PBD and a case of giant cell reparative granuloma of Paget's disease in Korea, where PBD is very rare.
Abdomen ; Africa ; Asia ; Bone Diseases ; Calcium ; Congenital Abnormalities ; Dexamethasone ; England ; Extremities ; Family Characteristics ; Fathers ; Giant Cells ; Granuloma ; Head ; Humans ; Ileum ; Korea ; Mandible ; Microscopy ; Middle Aged ; Middle East ; Nuclear Family ; Osteocalcin ; Osteoclasts ; Pedigree ; Prevalence ; Scandinavian and Nordic Countries ; Wills ; Young Adult

Influenza virus culture was performed in 149 patients with influenza-like illness who were admitted or visited to the Department of Pediatrics, Asan Medical Center from january, 1991 to March, 1991. The results were as follows; 1) Of the 149 patients, influenza virus were isolated in the 15 cases. 15 isolates were characterized by the WHO Collaborating Center for influenza: 7 cases were very similar to influenza A/Taiwan/1/86 (H1N1), 1 case was A/Beijing/353/89 (H3N2), 7 cases were B/Guangdon-g/55/89. 2) The age of 15 patients who were confirmed by viral isolation was between 11 months to 10 years. 3) The most common clinical symptoms were fever, vomiting, cough, nausea in deceasing order. 4) Of the total 149 patients, Reye syndrome occured in two patients and myositis occured in one: Influenza A/Taiwan/1/86 (H1N1) virus was isolated in one Reye syndrome patient.
Chungcheongnam-do ; Cough ; Fever ; Humans ; Influenza, Human* ; Myositis ; Nausea ; Orthomyxoviridae ; Pediatrics ; Reye Syndrome ; Seoul* ; Vomiting