It has been reported that gonadotropins promoted phosphorylation of ERK/MAPK in granulosa cells. However, little is known about the effects of gonadotropin on ERK activity in theca cells. This study ...explores how LH/forskolin controls ERK phosphorylation in cultured bovine theca cells. Effects of ERK on steroidogenesis were also investigated. Phosphorylation of ERK in bovine theca cells was augmented by LH and forskolin in 5 min; it decreased thereafter below basal levels in 20 min. Nevertheless, phosphorylation of the ERK kinase, MEK, was unaffected. Addition of H89 (a protein kinase A inhibitor) significantly reduced the effect of LH/forskolin on ERK phosphorylation. A potent MEK inhibitor PD98059 eliminated ERK phosphorylation and augmented progesterone production concomitantly with the elevation of intracellular steroidogenic acute regulatory protein mRNA in LH/forskolin-stimulated theca cells. In contrast to progesterone production, androgen production was diminished significantly by inhibition of ERK with decreased intracellular P450c17 mRNA levels. Taking these results together, we conclude that LH/cAMP leads to phosphorylation of ERK in a biphasic manner through MEK-independent pathway in bovine theca cells. Protein kinase A-induced phosphatase could possibly contribute to the phosphorylation process. Furthermore, modulation of ERK phosphorylation involves control of thecal steroidogenesis via modulation of the expression of steroidogenic acute regulatory protein and P450c17.
Hyperpigmentations are a serious concern addressed by both the medical community and the cosmetic industry through the development of agents that block melanin biosynthesis. In this study, we found ...that 2-amino-3H-phenoxazin-3-one (APO), isolated from extracts of the edible mushroom Agaricus bisporus Imbach, exhibited potent inhibitory effects on melanogenesis in B16 cells, a murine melanoma cell line. APO inhibited melanin biosynthesis at 1,000 times lower concentrations (IC
50
=1.31±0.08 μM) than kojic acid (IC
50
=1.31±0.13 mM), without causing cellular toxicity. APO did not directly inhibit the enzyme activity of tyrosinase, the rate-limiting melanogenic enzyme. Further study showed that APO inhibited the protein expression of tyrosinase and microphthalmia-associated transcription factor (MITF), a melanogenic transcription factor that regulates the expression of tyrosinase. These results suggest that APO is a promising depigmenting agent with both therapeutic and cosmetic value in preventing melanogenesis.
We implemented cipher primitive RSA for SH7265 processor that has 2 core architecture. Assigning each processors to appropriate functions, as a result, we could speed up the cipher operations by 5.41 ...compared to straight forward coding and 1.48 to single chip mode CRT coding.
The novel lipopeptide antibiotic A21978C complex is active against Gram-positive organisms. This complex consists of a common peptide nucleus with various lipid acyl groups at the N-terminus ...characteristic of each individual factor. The fatty acid acyl group is removed by incubation of the A21978C complex with Actinoplanes utahensis to give the peptide nucleus. This peptide nucleus has the same amino acid sequence as A21978C. New analogs of A21978C were synthesized by acylation of the N-terminus of a tert-butoxycarbonyl (tert-BOC)-protected nucleus and subsequent deprotection. 1H NMR showed that the newly introduced acyl group was at the desired N-terminus. Three major groups of analogs were synthesized bearing fatty acid acyl, amino-aroyl and extended peptide side chains. Each analog was evaluated for antimicrobial activity and acute toxicity. Of these analogs, the n-decanoyl analog of A21978C (LY146032) gave the best survival in the mouse acute toxicity test at a high dose of 1,000 mg/kg, iv and was chosen for further study. This analog has been named daptomycin.
A compact 50 MW rf source, an upgraded version of an existing rf source of the PF linac, has been developed for the KEKB project. The rf pulse-width requirement for the 50 MW klystron is 4 μs in ...order to be used with SLED-type rf compressors. On the basis of a computer simulation, the existing 30 MW klystron has succeeded to produce more than 51 MW at a 310 kV beam voltage with a 4 μs rf pulse width by optimizing the focusing magnetic field. Based on this result, we have designed and tested a new compact 50 MW klystron, the interaction region of which is the same as that of the 30 MW tube. In order to realize a practically reliable tube, we enlarged the cathode diameter, the gun housing and the insulation ceramic-seal. As a result, we have succeeded in obtaining a 50 MW output power with an rf pulse width of 4 μs and a more than 60 MW output power with an rf pulse width of 2 μs from this klystron. Compatibility between the 30 MW klystron and the 50 MW klystron has been aimed at for a socket assembly, such as a focusing electromagnet and a pulse-transformer assembly, with only a small change. These could lead to a compact rf source, which would save on upgrading costs. We can expect an easy construction method, which could be required to be conducted during an interval of machine operation for the Photon Factory.
This study was designed to compare venoarterial (VA) with venovenous (VV) access in the cerebral circulation of newborn infants during extracorporeal membrane oxygenation (ECMO). Among 14 infants ...with VA ECMO, 7 had no intracranial complications (group 1), while the others (group 2) developed intracranial hemorrhage (ICH). In contrast, among 19 infants with VV ECMO, only 1 developed ICH. Serial echocardiograms were performed before and after 1, 6, 12, and 24 h and 2 and 3 days of ECMO. The mean cerebral blood flow (CBF) velocities were measured in the anterior cerebral artery (ACA), right and left internal carotid arteries (Rt, Lt-ICA), basilar artery (BA), and right and left middle cerebral arteries (Rt, Lt-MCA). Ejection fraction (EF), cardiac output (CO), and stroke volume (SV) were also measured using standard echography. The velocity levels in the ACA, Rt-MCA, and Lt-MCA in VA ECMO were lower than those in VV ECMO, while those in the Lt-ICA and BA in VA ECMO were higher than those in VV ECMO. The EF, CO, and SV were lower in cases of VA ECMO than in VV ECMO. In cases of VA ECMO, there were no differences between groups 1 and 2 in velocities in the ACA, Rt-ICA, or Lt-ICA. However the velocities in group 2 in the BA, Rt-MCA, and Lt-MCA were lower than those in group 1 before and during ECMO. Similarly, the EF, CO, and SV were lower in group 2 (12.0%-31.0%, 0. 10-0.32 l/min, and 0.66-1.55 ml, respectively) than in group 1 (29. 5%-49.3%, 0.25-0.63 l/min, and 2.15-3.85 ml) during ECMO. However, in the infants on VV ECMO the CBF was either maintained or gradually increased before and during ECMO. Their cardiac parameters were: EF 46.1%-53.0%, CO 0.43-0.52 l/min, and SV 2.72-3.84 ml during ECMO. It is concluded that in VA ECMO CBF velocities, particularly in infants who developed ICH, decreased after the onset of ECMO in association with poor cardiac function, while in VV ECMO they were stable, probably due to normal systemic hemodynamics and cardiac function.
Background. Prognosis of hepatocellular carcinoma (HCC) with tumor thrombus in the main portal vein (MPV), inferior vena cava (IVC), or extrahepatic bile duct (EBD) treated by conventional therapies ...has been considered poor. This study aimed to evaluate the efficacy of hepatic arterial infusion chemotherapy after surgical resection as an adjuvant therapy or as a treatment for intrahepatic recurrence of HCC with tumor thrombus in MPV, IVC, or EBD. Methods. Nineteen patients with HCC and tumor thrombus in the MPV, IVC, or EBD who underwent hepatectomy with thrombectomy were reviewed retrospectively. Results. The overall 3-year survival rate was 48.5%. Two patients with postoperative residual tumor thrombus died within 6 months owing to rapid progression of the residual tumor thrombus. Five patients survived more than 5 years after their operations. Tumors disappeared completely in 3 patients after hepatic arterial infusion chemotherapy with a combination of cisplatinum and 5-fluorouracil, and the longest survival period was 17 years and 11 months in a patient with EBD thrombus. Conclusions. If hepatic reserve is satisfactory, an aggressive surgical approach combined with chemotherapy seems to be of benefit for patients having HCC with tumor thrombus in the MPV, IVC, or EBD. (Surgery 2002;131:300-10.)
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