[Relationship between the central alpha-adrenoceptors and central effects of morphine (author's transl)].
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Adrenergic alpha-Agonists↗
Biomedical subjects
Y Jin
Publications and source records attributed to Y Jin.
[The inhibitory effect of succinic acid on the central nervous system (author's transl)].
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Animals↗
Biotransformation of BOF-4272, a sulfoxide-containing drug, in the cynomolgus monkey.
BOF-4272, (+/-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one), is a new drug intended for the treatment of hyperuricemia. This report describes the pharmacokinetics and detailed metabolic pathways of BOF-4272 in the cynomolgus monkey, which were investigated using the metabolites found in plasma, urine, and faeces after intravenous and oral administration. M-4 was the main metabolite in plasma after intravenous administration. M-3 and M-4 were the main metabolites in plasma after oral administration. The Cmax and AUC(0-t) of M-4 were the highest of all the metabolites after intravenous administration. The Cmax and AUC(0-t) of M-3 were the highest of all the metabolites, and those of M-4 were the second highest, after oral administration. M-4 and M-3 were the main metabolites detected in urine and faeces, respectively, after intravenous administration, with M-4 and M-3 at 47.2% in urine and 19.1% in faeces, respectively, within 120 h after administration. M-4 was the only metabolite detected in urine after oral administration, at about 5% within 120 h after administration. M-3 was detected in faeces at 17.0% within 120 h after oral administration. These results suggest that, in the cynomolgus monkey, BOF-4272 is rapidly biotransformed to a main metabolite (M-4, a sulphoxide-containing metabolite of BOF-4272) and that M-4 is mainly excreted in urine and possibly also in bile, with subsequent conversion to M-3 by the intestinal flora. It is expected that the biotransformation of BOF-4272 would be similar in healthy human volunteers.
Animals↗
Langerhans' cell histiocytosis as a cause of periportal abnormal signal intensity on MRI.
Three cases of hepatic Langerhans' cell histiocytosis (LCH) manifesting as periportal abnormal signal intensity on magnetic resonance images are described. One case also demonstrated intrahepatic bile duct dilatation due to secondary sclerosing cholangitis. Hepatic involvement of LCH could be included in the differential diagnosis of periportal abnormal signal intensity in children.
Histiocytosis, Langerhans-Cell↗
The decline of atrial natriuretic peptide (ANP) gene expression in older rats and the effects of ginsenoside on ANP gene expression.
1. The levels of atrial natriuretic peptide(ANP) gene expression in rat atria at 2-3 and 14-18 months of age and the effects of ginsenosides on r-ANP gene expression by determining the concentration of ANP-mRNA were investigated. The male and female rats were abdominally (i.p.) injected with aqueous solution of ginsenosides prepared from ginseng stems and leaves (G-PSL) and ginseng roots (G-PR), 50 mg/kg body wt, once a day for 7 days. Atria total RNA was extracted by the cold phenol method. The ANP-mRNA contents were determined using the Northern blot and dot blot hybridization technique with alpha-32*P-labelled r-prepro-ANP-cDNA probe. 2. The ANP-mRNA contents of 14-18 month rats were remarkably less than that of 2-3 month rats. The levels of male and female rats' atria at 14-18 months were about 15 and 60%, the content of male and female rats at 2-3 months respectively. 3. G-PSL and G-PR increased the ANP-mRNA content of male rats at 14-18 months 1- and 2-fold, respectively, whereas G-PSL and G-PR decreased the ANP-mRNA content in male rats of age 2-3 months. 4. These results revealed that the ANP gene expression declined during ontogenic ageing development and ginsenosides possessed anti-ageing effects in the heart endocrineous function aspect.
Aging↗
Phenotypic marker and cytotoxic potential of hepatic lymphocytes isolated from rejected livers.
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Graft Rejection↗
Perioperative donor bone marrow infusion in cadaver kidney transplant recipients.
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Bone Marrow Transplantation↗
[Radiotherapy and intra-arterial chemotherapy of locally advanced hepatocellular carcinoma. Analysis of prognostic factors].
UNLABELLED: Prognostic factors in the treatment of local advanced hepatocellular carcinoma with radiotherapy, transcatheter arterial embolization and arterial infusion. PURPOSE: The treatment effects of radiotherapy and combination modality therapy for the local advanced hepatocellular carcinoma (HCC) were retrospectively reviewed. MATERIAL AND METHODS: Three hundred and fifty-six patients of HCC (187 recurrent cases after surgical resection) were treated by 1) radiotherapy only; 2) Bi-therapeutic method: hepatic artery ligation (HAL) and/or hepatic artery embolization (HAE) plus radiotherapy; and 3) tri-therapeutic method (bi-therapeutic method plus hepatic artery infusion) from 1975 to 1996. Kaplan-Meier method has been used to evaluate the survival rates. RESULTS: There were no significant differences among these three treatment groups in the symptom relief rate, but the mean relief time period was much shorter in radiotherapy alone group (2.5 vs 44 months, P < 0.05). A lower tumor response rate was found in the radiotherapy alone group (P < 0.05), although that was similar for both primary or recurrent tumors (P > 0.05). There were evident differences in five-year survivals among these three treatment groups: 0% for radiotherapy alone, 22.8% for bi-therapeutic method and 38.8% for tri-therapeutic method (P < 0.01). The prognosis was influenced by Okuda classification. CONCLUSION: Non-resectable local advanced HCC can be treated by the combination modality therapy, including radiotherapy, with a quite high cure rate. Radiotherapy alone can relief the symptoms.
Adult↗
A statistical-based approach to assessing the fidelity of combinatorial libraries encoded with electrophoric molecular tags. Development and application of tag decode-assisted single bead LC/MS analysis.
A statistical sampling protocol is described to assess the fidelity of libraries encoded with molecular tags. The methodology, termed library QA, is based on the combined application of tag decode analysis and single bead LC/MS. The physical existence of library compounds eluted from beads is established by comparing the molecular weight predicted by tag decode with empirical measurement. The goal of sampling is to provide information on overall library fidelity and an indication of the performance of individual library synthons. The minimal sampling size n for library QA is l0 x the largest synthon set. Data are reported as proportion (p) +/- lower and upper boundary (lb-ub) computed at the 95% confidence level (alpha = 0.05). As a practical demonstration, library QA was performed on a 25,200-member library of statine amides (size = 40 x 63 x 10). Sampling was conducted three times at n approximately 630 beads per run for a total of 1902 beads. The overall proportions found for the three runs were consistent with one another: p = 84.4%, lb-ub = 81.5-87.2%; p = 83.1%, lb-ub = 80.2-85.95; and p = 84.5%, lb-ub = 81.8-87.3%, suggesting the true value of p is close to 84% compound confirmation. The performance pi of individual synthons was also computed. Corroboration of QA data with biological screening results obtained from assaying the library against cathepsin D and plasmepsin II is discussed.
Journal Article↗
Control of type-D GABAergic neuron differentiation by C. elegans UNC-30 homeodomain protein.
The Caenorhabditis elegans gene unc-30 is required for the development and functioning of the 19 inhibitory GABAergic (gamma-aminobutyric-acid-secreting) type D motor neurons, which control locomotion. In unc-30 mutants the D neurons lack GABA and have defects in axonal pathfinding and synaptic connections (J. White, personal communication). We report here that unc-30 encodes a homeodomain protein that is present in the nuclei of the D neurons at high levels in young larvae, in which the motor circuitry is formed, and at low levels in older animals. The UNC-30 protein is also present in six non-GABAergic neurons and is absent from the seven non-D-type GABAergic neurons. Ectopic expression of unc-30 induced GABA expression in cells that are normally not GABAergic. We propose that unc-30 functions as a transcriptional regulator within the type D neurons to control their terminal differentiation and that unc-30 is sufficient in some but not all cell types to induce GABA expression.
Amino Acid Sequence↗
Evaluation of urinary 1-hydroxypyrene, S-phenylmercapturic acid, trans,trans-muconic acid, 3-methyladenine, 3-ethyladenine, 8-hydroxy-2'-deoxyguanosine and thioethers as biomarkers of exposure to cigarette smoke.
The objective was to evaluate the utility of urinary 1-hydroxypyrene (1-OHP), S-phenylmercapturic acid (S-PMA), trans,trans-muconic acid (t,t-MA), 3-methyladenine (3-MeAd), 3-ethyladenine (3-EtAd), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and thioethers as biomarkers for assessing the exposure in adult smokers who switched from smoking conventional cigarettes to candidate potential reduced exposure products (PREP) or who stopped smoking. Two electrically heated smoking systems (EHCSS) were used as prototype cigarettes that have significant reductions in a number of mainstream smoke constituents as measured by smoking machines relative to those from conventional cigarettes. Urine samples were collected from a randomized, controlled, forced-switching study in which 110 adult smokers of a conventional cigarette brand (CC1) were randomly assigned to five study groups. The groups included the CC1 smoking group, a lower-tar conventional cigarette (CC2) smoking group, EHCSS1 group, EHCSS2 group and a no smoking group that were monitored for 8 days. Biomarkers were measured at baseline and day 8. The daily excretion levels of these biomarkers were compared among the groups before and after switching, and the relationships between the daily excretion levels of these biomarkers and cigarette smoking-related exposure were investigated using Pearson product-moment correlation and multiple regression analyses. It was concluded that under controlled study conditions: (1) 1-OHP, S-PMA and t,t-MA are useful biomarkers that could differentiate exposure between smoking conventional and EHCSS cigarettes or between smoking conventional cigarettes and no smoking; between S-PMA and t,t-MA, the former appeared to be more sensitive; (2) 3-MeAd could only differentiate between smoking conventional cigarettes and no smoking; the results for 3-EtAd were not conclusive because contradictory results were observed; (3) 8-OHdG had a questionable association with smoking and therefore the utility of this biomarker for smoking-related exposure could not be established; and (4) urinary excretion of thioethers as a biomarker lacked sensitivity to demonstrate a clear dose-response relationship in conventional cigarette smokers, although it could differentiate the excretion levels between those subjects who smoked a conventional cigarette and those who stopped smoking.
8-Hydroxy-2'-Deoxyguanosine↗
PKC-dependent phosphorylation may regulate the ability of connexin43 to inhibit DNA synthesis.
Phosphorylation affects several biological functions of connexin43 (Cx43), although its role on Cx43-mediated inhibition of DNA synthesis is not known. Previous studies showed increased Cx43 phosphorylation on serine in response to growth factor stimulation of cardiomyocytes, mediated by protein kinase C-epsilon (PKCepsilon). Here we report that activation of PKCepsilon is also necessary for stimulation of cardiomyocyte DNA synthesis and mitosis. We have investigated the participation of specific serine residues that are putative PKC targets in producing phosphorylated Cx43 species and also in regulating DNA synthesis in cardiomyocytes. Interference with the PKC signaling system and/or the phosphorylation of specific amino-acids of Cx43 may allow regulation of the mitogenic response.
Animals↗
The loach Misgurnus anguillicaudatus reduces amino acid catabolism and accumulates alanine and glutamine during aerial exposure.
The loach Misgurnus anguillicaudatus inhabits rice fields in Southern China. It encounters drought during summer and ammonia loading during agricultural fertilization. In the laboratory, aerial exposure led to decreases in its ammonia and urea excretion. Ammonia accumulated to very high levels in the muscle and liver. Urea synthesis through the ornithine-urea cycle was not involved in ammonia detoxification in M. anguillicaudatus. However, M. anguillicaudatus was capable of partial amino acid catabolism leading to the accumulation of alanine in the first 24 h of aerial exposure. This was apparently coupled to a possible decrease in protein/amino acid catabolism. These are not detoxification mechanisms but mechanisms that avoid internal fouling by ammonia. Misgurnus anguillicaudatus was also capable of detoxifying internally produced ammonia in part to glutamine, which appears to be an important adaptation after 24 h of aerial exposure. However, unlike the case of the marble goby (Oxyeleotris marmoratus), there was no alteration to the kinetic properties of the hepatic glutamine synthetase. During dry seasons, M. anguillicaudatus moves actively on land until it encounters soft mud in which it can bury itself through several strong wriggling actions of the body. Hence, it is possible that M. anguillicaudatus uses partial amino acid catabolism to fuel its short period of activities on land and switches to the formation of glutamine to detoxify internally produced ammonia when it remains relatively inactive in the mud.
Adaptation, Physiological↗
Multilineage differentiation of ectomesenchymal cells isolated from the first branchial arch.
Cranial neural crest-derived ectomesenchymal cells may be pluripotent stem cells that are capable of generating a range of phenotypes. The fate of these cells appears to be determined in part by intrinsic genetic programs and also by the influence of extracellular signals in the local environment. The extent of lineage determination once neural crest cells have migrated to the first branchial arch is not clear, although branchial arch pattern is not thought to be the result of crest predetermination. The aim of the present study was to test the hypothesis that ectomesenchymal cells of the first branchial arch show properties of pluripotent stem cells, the lineage of which may be directed by specific molecular signaling. Ectomesenchymal cells were enzymatically isolated from the mandibular processes of BALB/c mice and maintained in an undifferentiated state while cultured with leukemia inhibitory factor or induced to differentiate by lineage-specific induction factors or growth conditions, including transforming growth factor beta, forskolin, and a mineralization-promoting medium. Morphological observations and immunocytochemistry demonstrated that cells could be induced to differentiate into smooth muscle cells, glial cells, and osteoblasts, respectively. In the presence of the mineralization-promoting medium, alkaline phosphatase activity increased significantly and mineralization nodules formed. The data reported support the concept that many, although not all, first branchial arch-derived ectomesenchymal cells show properties of multipotent stem cells, the subsequent fate of which can be influenced by induction factors and growth conditions. Some cells, however, showed a degree of commitment with respect to their fate. The possible application of first branchial arch-derived stem cells to tissue engineering of the orofacial tissues should involve consideration of the developmental stage of cell harvesting and the desired cell fate.
Animals↗
Hydroxyethyl starch inhibits intestinal production of cytokines and activation of transcription factors in endotoxaemic rats.
We studied the effect of hydroxyethyl starch (HES) on intestinal production of cytokines and activation of transcription factors in sepsis. Septic rats, induced by intraperitoneal lipopolysaccharide (LPS) (5 mg/kg), were treated with intravenous HES (16 ml/kg) or saline (64 ml/kg). Rat ileal tissues were collected at 2 h, 3 h or 6 h after LPS challenge. Levels of tumour necrosis factor alpha (TNF-alpha), interleukin (IL) 1beta, IL-6, IL-8 and IL-10, cytokine mRNAs, activities of nuclear factor kappa-B (NF-KB) and activator protein-1 (AP-1), and the number of ileal myeloperoxidase (MPO)-positive cells were determined for each group. HES significantly reduced the LPS-induced increase in intestinal levels of TNF-alpha, IL-1beta, IL-6, IL-8 and their corresponding mRNAs. HES also decreased the number of MPO-positive cells induced by LPS and inhibited activation of NF-kappaB and AP-1. The results suggest that in sepsis, HES may down-regulate intestinal pro-inflammatory cytokine production via suppression of NF-kappaB and AP-1 activation.
Animals↗
Indoor air pollution and respiratory health in urban and rural China.
During the summer of 1999, information about respiratory health outcomes and relevant covariates was collected from 3,709 Chinese adults in Beijing, Anqing City, and rural communities in Anqing Prefecture. Indoor PM10 and SO2 were measured in a random sample of selected households. Using logistic regression and controlling for important covariates (excluding PM10 and SO2) and familial intraclass correlation, highly significant differences were found between study areas in the prevalences of chronic cough, chronic phlegm, wheeze, and shortness of breath, but not physician-diagnosed asthma. Generally, the lowest prevalence of respiratory symptoms was observed in Anqing City, a higher prevalence in rural Anqing, and the highest prevalence in Beijing. Median indoor concentrations of PM10 were similar in Anqing City (239 microg/m3) and rural Anqing (248 microg/m3), but much higher in Beijing (557 microg/m3). Median indoor concentrations of SO2 were similar in all three areas (Beijing: 14 microg/m3, Anqing City: 25 microg/m3, rural Anqing: 20 microg/m3).
Adult↗
Phenanthrene degradation in soils co-inoculated with phenanthrene-degrading and biosurfactant-producing bacteria.
Contaminant sorption within the soil matrix frequently limits biodegradation. However, contaminant bioavailability can be species-specific. This study investigated bioavailability of phenanthrene (PHE) to two PHE-degrading bacteria (Pseudomonas strain R and isolate P5-2) in the presence of rhamnolipid biosurfactant and/or a biosurfactant-producing bacterium, Pseudomonas aeruginosa ATCC 9027. Pseudomonas strain R mineralized more soil-sorbed PHE than strain P5-2, but in aqueous cultures the rate and extent of PHE mineralization by P5-2 exceeded that by P. strain R. In Fallsington sandy loam (fine-loamy, mixed, active, mesic Typic Endoaquult) (high PHE-sorption capacity) the addition of rhamnolipid increased PHE mineralization by P. strain R. Phenanthrene mineralization in soils inoculated with P5-2 was minimal and no enhancement in PHE degradation was observed when biosurfactant was added. Co-inoculation of Fallsington sandy loam with the biosurfactant producer did not affect PHE mineralization by isolate P5-2, but significantly enhanced PHE mineralization by P. strain R. The enhancement of PHE mineralization could not be explained by P. aeruginosa-mediated PHE degradation. The addition of rhamnolipid at concentrations above the critical micelle concentration (CMC) resulted in enhanced PHE release from test soils. These results suggest that the PHE-degrading strains were able to access different pools of PHE and that the biosurfactant-enhanced release of PHE from soils did not result in enhanced biodegradation. The results also demonstrated that bacteria with the catabolic potential to degrade sorbed hydrophobic contaminants could interact commensally with surfactant-producing strains by an unknown mechanism to hasten the biodegradation of aromatic hydrocarbons. Thus, understanding interactions among microbes may provide opportunities to further enhance biodegradation of soil-bound organic contaminants.
Adsorption↗
Increased expression of platelet-derived endothelial cell growth factor in human hepatocellular carcinomas correlated with high Edmondson grades and portal vein tumor thrombosis.
Platelet-derived endothelial cell growth factor (PD-ECGF), identical to thymidine phosphorylase, has been reported as an angiogenic factor in human malignancies. However, the role of PD-ECGF in human hepatocellular carcinoma (HCC) is still unconfirmed. Herein, we studied the expression of PD-ECGF in 27 human HCC cases by immunohistochemistry, to clarify the relationship to tumor angiogenesis. The immunoreaction of PD-ECGF in HCC cells was scored in both the staining percentage and intensity. CD34, an endothelial cell marker, was used to evaluate the intratumoral microvessel density (IMVD). PD-ECGF expression was noted in carcinoma cells in 14 (51.9%) of 27 HCCs. In these cases, the carcinoma cells showed heterogeneous staining in both the nucleus and cytoplasm. Tumor-associated stroma cells and infiltrating lymphocytes were also stained. Kupffer cells in non-tumor areas were strongly positive. Statistically, the expression of PD-ECGF increased in HCC specimens with high Edmondson grades (III-IV) or portal vein tumor thrombosis (PVTT) (P<0.05). Additionally, the IMVD of PD-ECGF-positive HCC specimens (136.071+/-31.008, mean +/- SD) was higher than that of the PD-ECGF-negative HCC specimens (61.077+/-15.795) (P<0.05). These findings may suggest that PD-ECGF is one of the angiogenic factors in human HCCs. Furthermore, with the increasing expression of PD-ECGF, HCC cells show poor differentiation and invasive behavior.
Aged↗