Biomedical subjects
Publications and source records attributed to C Li.
Small vessel telangiectasias are commonly seen in clinical dermatology. This article focuses on the evaluation of these patients and treatment. The types of sclerosing agents and the techniques of sclerotherapy are discussed in detail.
Type XI collagen is predominantly found in cartilage. However, expression of the pro-alpha2(XI) collagen gene (COL11A2) has recently been detected in various non-cartilaginous tissues. We identified the differentiation stage at which COL11A2 was expressed in cultured fetal rat calvarial (FRC) cells and in rat femoral fracture calluses in order to investigate the involvement of COL11A2 during bone formation in vitro and in vivo. We also studied the alternative splicing of exons 6-8 in FRC cells and fracture calluses. In FRC cells, mineralized nodules stained with von Kossa stain were observed from day 9 after confluence. COL11A2 was highly expressed on days 0 and 5, but the expression levels were rapidly decreased on day 9 by Northern blot analysis. During rat femoral fracture repair, intramembranous ossification proceeded and newly formed woven bone was observed on the cortex on day 7 after fracture. In situ hybridization showed that COL11A2 signals were detected in osteoblastic cells in the newly formed woven bone. According to the maturation and remodeling of the woven bone into the trabecular bone, the distribution of the signal for COL11A2 mRNA was limited to the superficial osteoblastic cells of the newly formed trabecular bone. These results demonstrated that COL11A2 was expressed in relatively immature osteoblastic cells during bone formation in vitro and in vivo. RT-PCR showed that the shortest band corresponding to mRNA lacking exons 6-8 was clearly detected when using RNA from soft calluses. In contrast, the largest band corresponding to mRNA with exons 6-8 was predominant when using RNA from FRC cells or from hard calluses on days 7 and 14. These results indicate that the splicing pattern of exons 6-8 in osteoblastic cells is different from the pattern in chondrocytes.
The olfactory system consists of the primary olfactory nerves in the nasal cavity, the olfactory bulbs and tracts, and numerous intracranial connections and pathways. Diseases affecting the sense of smell can be located both extracranially and intracranially. Many sinonasal inflammatory and neoplastic processes may affect olfaction. Intracranially congenital, traumatic, and neurodegenerative disorders are usually to blame for olfactory dysfunction. The breadth of diseases that affect the sense of smell is astounding, yet the imaging ramifications have barely been explored.
The LAMB1 gene encodes the laminin beta1 subunit of laminin, an extracellular matrix protein. Using several transgenic mouse lines containing various lengths of the LAMB1 promoter driving lacZ reporter gene expression, regions of LAMB1 promoter that contain cis-acting DNA regulatory element(s) have been identified. The 3.9LAMB1betagal transgene is expressed in various tissues during development. LAMB1 transgene expression is observed in a selective set of nephrons of the neonatal and adult kidneys. The cis-acting DNA regulatory elements responsible for LAMB1 transgene expression in ovaries and in juvenile kidneys are present between -'1.4 and -0.7 kb relative to the transcription start site, while those of adult kidneys are located between -2.5 and -1.4 kb. The LAMB1 transgene is also expressed in the epididymis of 1 week old transgenic mice. Mutation of the retinoic acid response element (RARE) in the context of the 3.9LAMB1betagal transgene results in loss of LAMB1 transgene expression in all tissues. Thus, sequences between -2.5 and -0.7 kb plus the RARE are required for appropriate expression of the LAMB1 transgene in mice.
Colicins kill E. coli by a process that involves binding to a surface receptor, entering the cell, and, finally, intoxicating it. The lethal action of colicin E3 is a specific cleavage in the ribosomal decoding A site. The crystal structure of colicin E3, reported here in a binary complex with its immunity protein (IP), reveals a Y-shaped molecule with the receptor binding domain forming a 100 A long stalk and the two globular heads of the translocation domain (T) and the catalytic domain (C) comprising the two arms. Active site residues are D510, H513, E517, and R545. IP is buried between T and C. Rather than blocking the active site, IP prevents access of the active site to the ribosome.
Ligand-induced phosphorylation of the receptor-regulated Smads (R-Smads) is essential in the receptor Ser/Thr kinase-mediated TGF-beta signaling. The crystal structure of a phosphorylated Smad2, at 1.8 A resolution, reveals the formation of a homotrimer mediated by the C-terminal phosphoserine (pSer) residues. The pSer binding surface on the MH2 domain, frequently targeted for inactivation in cancers, is highly conserved among the Co- and R-Smads. This finding, together with mutagenesis data, pinpoints a functional interface between Smad2 and Smad4. In addition, the pSer binding surface on the MH2 domain coincides with the surface on R-Smads that is required for docking interactions with the serine-phosphorylated receptor kinases. These observations define a bifunctional role for the MH2 domain as a pSer-X-pSer binding module in receptor Ser/Thr kinase signaling pathways.
Glucans are fungal cell wall polysaccharides which stimulate innate immune responses. We determined the minimum unit ligand that would bind to glucan receptors on human U937 cells using laminarin-derived pentaose, hexaose, and heptaose glucan polymers. When U937 membranes were pretreated with the oligosaccharides and passed over a glucan surface, only the heptasaccharide inhibited the interaction of glucan with membrane receptors at a K(d) of 31 microM (95% CI 20-48 microM) and 100% inhibition. However, the glucan heptasaccharide did not stimulate U937 monocyte NFkappaB signaling, nor did it increase survival in a murine model of polymicrobial sepsis. Laminarin, a larger and more complex glucan polymer (M(w) = 7700 g/mol), only partially inhibited binding (61 +/- 4%) at a K(d) of 2.6 microM (99% CI 1.7-4.2 microM) with characteristics of a single binding site. These results indicate that a heptasaccharide is the smallest unit ligand recognized by macrophage glucan receptors. The data also indicate the presence of at least two glucan-binding sites on U937 cells and that the binding sites on human monocyte/macrophages can discriminate between glucan polymers. The heptasaccharide and laminarin were receptor antagonists, but they were not receptor agonists with respect to activation of NFkappaB-dependent signaling pathways or protection against experimental sepsis.
The Langmuir-Blodgett (LB) films of octadecanoyl ester of 1-(2-carboxyethyl) thymine deposited from pure water and aqueous adenosine subphases were investigated by ultraviolet-visible (UV-vis), Fourier transform infrared-attenuated total reflection (FTIR-ATR), and Fourier transform surface-enhanced Raman scattering (FT-SERS) spectroscopy. The obtained spectral results indicate that the adenosine molecules in the subphase can be transferred onto solid substrates by LB techniques as a result of the formation of base pairs at the air/water interface. UV-vis spectra alternations indicated that, with increasing adenosine concentration in subphase, more adenosine molecules were recognized by nucleolipid monolayer and were transferred onto the quartz substrates. The closed-packing of the constituent molecules facilitates the photodimerization of the thymine moieties in the headgroup under ultraviolet irradiation. FTIR-ATR results suggest that the hydrocarbon chains of nucleolipid in the LB films deposited from pure water and aqueous adenosine take on a close-packed all trans conformation. By analyzing the FT-SERS spectra results, it can be deduced that the orientation of nucleobase in the headgroup is different before and after the recognition effect occurred. For LB film deposited from pure water, the nucleobases are lying flat on the silver substrates; whereas for LB film deposited from aqueous adenosine, the base pairs take an end-on adsorption on silver substrate.
The complex Co(p-DMABA)2Cl2 x 2H2O (p-dimethylaminobenzaldehyde, p-DMABA) was prepared from the solid-state reaction of a weak ligand p-DMABA and CoCl2 x 6H2O at lower heating temperature (60 degrees C). It is very difficult to obtain the title complex using solution reaction method, less than isolating single crystals. In order to determine the crystal structure of the title compound, we have to rely on the X-ray powder diffraction data. That is, the crystal structure can be solved directly from powder data, which crucial step is to constitute the structure model. Indirect spectroscopic methods, such as infrared and Raman spectroscopes, and further vibrational assignments made with the aid of normal coordinate calculations by using a modified Urey-Bradley force field, were analyzed to proposed molecular structure. One hundred and fifty-seven internal coordinates were established and 129 theoretical vibrational frequencies were calculated. An appropriate set of internal coordinates and force constants in the course of calculation were introduced, so that the calculated vibration frequencies are good agreement with the observed values. The average difference and the maximum deviation between theoretic and experimental frequencies are 2.44 and 8.0 cm(-1), respectively. Thus the normal coordinate analysis is a powerful tool to the molecular structure. Other structural and spectral properties are also discussed in this paper. The purpose of the present paper is to obtain a good structural model. This model was used as starting model for crystal structure determination from powder X-ray diffraction (XRD) data.
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Profiles of genistein, daidzein, genistin, daidzin, and their acetyl- and malonyl-beta-glycosides were determined in tofu as affected by temperature and time. Tofu was heated in water at 80, 90, and 100 degrees C for 0 (control), 10, 20, 30, and 40 min, and the contents of the isoflavones of interest were quantified using reversed-phase HPLC. Total isoflavone content decreased most likely due to leaching of isoflavones into the water. Because the content of the isoflavones of the genistein series was little affected by the treatments, the decrease in the total isoflavone content was almost exclusively due to a decrease of the daidzein series. Changes in the profile of the daidzein series suggest little decarboxylation of the malonylglycoside to the acetylglycoside, but considerable de-esterification of the malonyl- and acetylglycoside to the beta-glucoside. Strongly temperature dependent decreases of the aglycon suggest possible thermal degradation of daidzein in addition to losses due to leaching.
Tea has been proposed to have beneficial health effects which have been attributed to the polyphenolic compounds known as catechins. The bioavailability and biotransformation of these compounds, however, are not clearly understood. In this study, we used liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) to determine urinary glucuronidated and sulfated tea catechins and their metabolites (including methylated and ring-fission metabolites) based on the detection of deprotonated molecular ions and aglycone fragment ions. The compound resolution was achieved both chromatographically and mass spectroscopically. After green tea administration, the major conjugates appeared in human, mouse, and rat urine samples were identified as monoglucuronides and monosulfates of (-)-epigallocatechin (EGC) and (-)-epicatechin. We also found O-methyl-EGC-O-glucuronides and -O-sulfates and O-methyl-epicatechin-O-sulfates in human urine. (-)-5-(3',4',5'-Trihydroxyphenyl)-gamma-valerolactone (M4) and (-)-5-(3',4'-dihydroxyphenyl)-gamma-valerolactone (M6), the ring-fission metabolites of EGC and (-)-epicatechin, respectively, were also predominantly in monoglucuronide and monosulfate forms in the urine. In comparison to rats, the urinary metabolite profiles of tea catechins in mice resemble more closely to those in humans. This is the first report describing direct simultaneous analysis of multiple tea catechin conjugates in urine samples. This method will allow more thorough investigations of the biotransformation of tea polyphenols.
Cytokine oncostatin M (OM) has profound effects on proliferation and differentiation of breast cancer cells. OM treated cells show reduced growth rate and differentiated phenotypes. The mechanisms underlying the OM growth-inhibitory activity in breast cancer cells have not been fully elucidated. In this study, we investigated the OM-elicited signaling pathways in breast cancer cell lines MDA-MB231 and MCF-7. We show that OM rapidly activates the extracellular signal-regulated kinase (ERK) and the signal transducer and activator of transcription (STAT) 1 and 3 in both cell lines. Intriguingly, OM-induced growth inhibition and morphological changes in MDA-MB231 cells are completely abolished by inhibitors to ERK upstream kinase MEK (nitrogen/extracellular-regulated protein kinase kinase), but the MEK inhibitors have little effects on OM growth-inhibitory activity in MCF-7 cells. In addition, expressions of the cyclin kinase inhibitors p21 and p27 are strongly induced by OM in MCF-7 cells, but their expression is only slightly increased by OM in MDA-MB231 cells. These data together demonstrate that the growth-inhibitory activity of OM can be mediated by different signaling pathways in a cell line-specific manner. While the MEK/ERK pathway is the predominant signaling pathway that leads to the growth inhibition of MDA-MB231 cells, activation of additional signaling pathways are necessary for OM to exert its growth-inhibitory activity in MCF-7 cells.
PURPOSE: To compare the mucosal membrane transport of gabapentin and pregabalin in animal small intestine. METHODS: Uptake of the two drugs by brush-border membrane vesicles (BBMV) from rat and rabbit small intestine was studied as a function of temperature, uptake-medium sodium content, and intestinal region. Amino acid inhibition studies were conducted with pregabalin. RESULTS: Gabapentin uptake by rat and rabbit jejunal BBMV was sodium independent, whereas pregabalin uptake was sodium dependent. Uptake of both drugs in rabbit small intestinal vesicles was greater at 25 degrees C than at 4 degrees C in the absence of sodium and an additional increase in uptake was observed for pregabalin at 25 degrees C in the presence of sodium. Pregabalin uptake in rabbit duodenal, jejunal, and ileal BBMV was equivalent, whereas gabapentin uptake was greater in duodenal and ileal BBMV, compared with jejunal BBMV. Although inhibition is weak, a decrease in BBMV uptake of pregabalin is observed with coincubation of high concentrations of both neutral and basic amino acids. CONCLUSIONS: Amino acid carriers mediate the apical uptake of both drugs in the small intestine. Although gabapentin and pregabalin are structurally similar, their small intestinal mucosal uptake differs in sodium dependence and region dependence. Gabapentin uptake is likely mediated by system b0,+, whereas pregabalin uptake is also mediated by B0 and/or B0,+.
TTP and HUS are two disorders with many similarities. Though their first descriptions appeared at different time in history, there has been a trend among physicians to consider them as the same clinical entity. However, in recent years new research findings on the pathophysiology of TTP and HUS have revealed some differences between the two disorders. In this paper, we will review the current approaches to the clinical and laboratory diagnosis of TTP and HUS, as well as therapeutic strategies. We will also summarize the recent advances in three areas in the study of the pathophysiology of TTP and HUS, namely the newly discovered von Willebrand factor multimer-cleaving protease, endothelial cell apoptosis induced by serum from patients with TTP and atypical HUS and the activation of complement system. Since distinguishing and differentiating between TTP and HUS may help to develop more effective therapies targeted at key steps of the disease development, we will discuss possible ways of reclassifying the TTP-HUS disorders. In the end, we also present our views on possible future development.
A novel cDNA fragment was identified from a human fetal brain cDNA library by using the coding sequence of human BRI3 gene (Accession No. NM015379) as bait in a yeast two-hybrid screening. Then by 5'-RACE (rapid amplification of cDNA end) and electronic hybridization, we obtained a 1.9 kb contig which consists of a novel gene. It was designated as BRI3BP by the HUGO Nomenclature Committee. It contains an open reading frame encoding 251 amino acids. The calculated molecular weight of the deduced protein is 27.8 kU. The predicted isoelectric point is 9.48. Northern hybridization showed its mRNA was highly expressed in brain, kidney, and liver. By RH mapping, the BRI3BP gene was mapped to human chromosome 12q24.2-qter
Previous work has shown that stimulation of contraction in A7r5 smooth muscle cells with phorbol ester (PDBu) results in the disassembly and remodeling of the alpha-actin component of the cytoskeleton (Fultz et al., 2000, J Mus Res Cell Motil 21: 775-781). In the present study, we evaluated the effect of increasing intracellular calcium ion concentration [Ca2+]i by A23187 and thapsigargin on alpha- and beta-actin remodeling. The effects of A23187 and thapsigargin on cell contraction and actin remodeling were effectively identical. The two compounds caused contraction of A7r5 cells that was earlier in onset and more quickly completed than PDBu-induced contractions. Both the alpha- and beta-actin isoforms were incorporated into stress cables in the resting cell. During the interval of contraction, beta-actin cables shortened without evidence of disassembly. By comparison, the increase of [Ca2+]i resulted in partial or complete dissolution of alpha-actin cables without further remodeling. In addition, PDBu-mediated alpha-actin remodeling was blocked in the presence of A23187. Increased [Ca2+]i also caused dispersal of alpha-actinin but had no effect on the cellular distribution of talin suggesting the effect was selective for alpha-actin cytoskeletal structure. The incubation of cells in calcium-free media prevented alpha-actin dissolution by A23187/thapsigargin and also blocked PDBu-mediated remodeling. Finally, of six kinase inhibitors investigated, only ML-7 partially blocked the dissolution of alpha-actin cables by increased [Ca2+]i. The results suggest that the sustained elevation of [Ca2+]i beyond a threshold level initiates depolymerization of alpha-actin but not beta-actin. It further appears that PDBu-induced alpha-actin remodeling requires Ca2+ but increases of [Ca2+]i beyond a threshold level may inhibit this activity. The finding that ML-7 partially inhibits alpha-actin dissolution in the presence of A23187/thapsigargin may be suggesting that myosin light chain kinase (MLCK) plays a role in destabilizing alpha-actin structure in the activated cell.
A finely tuned balance of angiogenic inhibitors and inducers controls the activity of angiogenesis characterized by proliferation, migration and differentiation of endothelial cells. Among many angiogenic factors, basic fibroblast growth factor (bFGF) was first identified to be angiogenic whereas vascular endothelial growth factor A (VEGF-A) is an endothelial cell specific mitogen. In addition to being a specific mitogen, VEGF-A is also known as a vascular permeability factor. The majority of growth factors transduce their mitogenic signals from cell surface to nucleus where gene expression occurs. Whether these ligands utilize a distinct or a common molecular pathway to exert their biological effects on human endothelial cells remains elusive. We thus studied the expression profile of 884 human genes under the influence of either bFGF or VEGF-A alone in the context of human endothelial cells. A total of ninety-four genes were differentially regulated by more than two folds. The expression patterns of 32 genes are similar between the treatment of either factor alone whereas those of the remaining 62 genes are only regulated by one but not the other factor. Their function in the control of angiogenesis will be discussed and apoptotic signaling in the regulation of angiogenesis is also implicated.