Immunopathology of uveitis.
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Granulocytes↗
Biomedical subjects
Q Li
Publications and source records attributed to Q Li.
Differential translocation of protein kinase C isozymes by phorbol esters, EGF, and ANG II in rat liver WB cells.
The protein kinase C (PKC) family represents an important group of enzymes whose activation is associated with their translocation from the cytosol to different cellular membranes. In this study, the spatial distribution of PKC-alpha, -delta and -epsilon in rat liver epithelial (WB) cells has been examined by Western blot analysis after subcellular fractionation. Cytosolic, membrane, nuclear, and cytoskeletal fractions were obtained from cells stimulated with phorbol 12-myristate 13-acetate (PMA), angiotensin II (ANG II), or epidermal growth factor (EGF). PMA caused most of the PKC-alpha, -delta and -epsilon initially present in the cytosol to be transported to the membrane and nuclear fractions. In contrast, both ANG II and EGF induced only a minor translocation of PKC-alpha to the membrane fraction but caused a statistically significant membrane-directed movement of PKC-delta and -epsilon. Translocation of PKC-delta and -epsilon to the nucleus induced by ANG II and EGF was transient and quantitatively smaller than that induced by PMA. PKC-delta and -epsilon were present in the cytoskeleton of resting cells, but although PMA, ANG II, and EGF caused some changes in their content, these were variable, suggesting that the cytoskeleton fraction was heterogeneous. PKC depletion inhibited ANG II-induced mitogenesis and the sustained activation of Raf-1 and extracellular regulated protein kinase (ERK). However, although PKC depletion inhibited EGF-induced mitogenesis, the maximum EGF-induced activation of the ERK pathway was only slightly retarded. We hypothesize that PKC-delta and -epsilon are involved in mitogenesis via both ERK-dependent and ERK-independent mechanisms. These results support the notion that specific PKC isozymes exert spatially defined effects by virtue of their directed translocation to distinct intracellular sites.
Angiotensin II↗
Properties and purification of a glucose-inducible human fatty acid synthase mRNA-binding protein.
Glucose stabilizes the mRNA for human fatty acid synthase (FAS), an enzyme relevant to diverse human disorders, including hyperlipidemia, obesity, and malignancy. To determine the underlying mechanisms, RNA gel mobility shift assays were used to demonstrate that human Hep G2 cells contain a cytoplasmic factor that binds specifically to the 3'-terminus of the human FAS mRNA. D-Glucose increased RNA-binding activity by 2.02-fold (P = 0.0033), with activity peaking 3 h after glucose feeding. Boiling or treatment of extracts with proteinase K abolished binding. Ultraviolet cross-linking of the FAS mRNA-binding factor followed by SDS-PAGE resolved a proteinase K-sensitive band with an apparent molecular mass of 178 +/- 7 kDa. The protein was purified to homogeneity using nondenaturing polyacrylamide gels as an affinity matrix. Acid phosphatase treatment of the protein prevented binding to the FAS mRNA, but binding activity was unaffected by modification of sulfhydryl groups and was not Mg2+ or Ca2+ dependent. Deletion and RNase T1 mapping localized the binding site of the protein to 37 nucleotides characterized by the repetitive motif ACCCC and found within the first 65 bases of the 3'-UTR. Hybridization of the FAS transcript with an oligonucleotide antisense to this sequence abolished binding. These findings indicate that a 178-kDa glucose-inducible phosphoprotein binds to an (ACCCC)n-containing sequence in the 3'-UTR of the FAS mRNA within the same time frame that glucose stabilizes the FAS message. This protein may participate in the posttranscriptional control of FAS gene expression.
Base Sequence↗
Regulation of lung fibroblast tropoelastin expression by alveolar epithelial cells.
Epithelial-mesenchymal interactions are of critical importance during tissue morphogenesis and repair. Although the cellular and molecular aspects of many of these interactions are beginning to be understood, the ability of epithelial cells to regulate fibroblast interstitial matrix production has not been extensively studied. We report here that cultured alveolar epithelial cells are capable of modulating the expression of tropoelastin, the soluble precursor of the interstitial lung matrix component elastin, by lung fibroblasts. Phorbol ester-stimulated alveolar epithelial cells secrete a soluble factor that causes a time- and dose-dependent repression of lung fibroblast tropoelastin mRNA expression. This alveolar epithelial cell-mediated repressive activity is specific for tropoelastin, is effective on lung fibroblasts from multiple stages of development, and acts at the level of transcription. Partial characterization of the repressive activity indicates it is an acid-stable, pepsin-labile protein. Gel fractionation of alveolar epithelial cell conditioned medium revealed two peaks of activity with relative molecular masses of approximately 25 and 50 kDa. These data support a role for epithelial cells in the regulation of fibroblast interstitial matrix production.
Animals↗
Fos expression following isotonic volume expansion of the unanesthetized male rat.
Cardiopulmonary afferents, baroreceptor afferents, or atrial natriuretic peptide binding to circumventricular organs may mediate the central response to volume expansion, a condition common to pregnancy, exercise training, and congestive heart failure. This study used Fos immunocytochemistry to examine brain regions activated by volume expansion. Male Sprague-Dawley rats were infused with isotonic saline equal to 10% of their body weight in 10 min followed by a maintenance infusion of 0.5 ml/min for 110 min. Control animals received 2-h infusions at 0.01 ml/min. Five minutes after the start of volume expansion, central venous pressure of expanded animals was significantly greater than control animals. The volume-expanded group exhibited significantly greater Fos activation (P < 0.05) in the area postrema, nucleus of the solitary tract, caudal ventrolateral medulla, paraventricular nucleus, supraoptic nucleus, and perinuclear zone of the supraoptic nucleus. Double labeling indicates that oxytocinergic neurons in the supraoptic nucleus are activated. Neurons in brain regions known to inhibit both sympathetic activity and vasopressin release show increased Fos expression following isotonic volume expansion.
Animals↗
Stimulation of activin receptor II signaling pathways inhibits differentiation of multiple gastric epithelial lineages.
Activins are TGFbeta family members known to mediate a variety of developmental events. We examined the effects of activins on the self-renewing epithelial lineages present in gastric units of the adult mouse stomach. These lineages are descended from multipotent stem cells located in the midportion of each unit. The stem cell and its immediate descendants can be identified by their morphological features. Studies of knockout mice lacking activins A or B, and/or activin type II receptors (ActRII) revealed that ActRII-mediated signaling is not required for normal gastric epithelial morphogenesis or homeostasis. Mice homozygous for a null allele of the alpha-inhibin gene (inha[m1/m1]) develop gonadal sex cord stromal tumors that secrete large amounts of activins A and B. Analysis of inha(m1/m1) mice, with or without gonads, established that supraphysiological levels of activins block differentiation of preparietal to acid-producing parietal cells, differentiation of neck cells to pepsinogen-producing zymogenic cells, and terminal differentiation of mucus-producing pit cells. ActRII mRNA is normally present in pit, parietal, and zymogenic cells. inha(m1/m1)actRII(m1/m1) compound homozygotes develop activin-secreting gonadal tumors but have no abnormalities in their gastric epithelium, indicating that persistent stimulation of ActRII-dependent signaling pathways produces pleiotrophic effects on gastric epithelial differentiation. When a lineage-specific promoter is used to ablate mature parietal cells with an attenuated diphtheria toxin A fragment in transgenic mice, there is increased proliferation of the multipotent gastric stem cell and its committed daughters and subsequent development of gastric neoplasia. Parietal cell loss in inha(m1/m1) mice is not associated with this proliferative response. These different responses to parietal cell loss suggest that stimulation of ActRII-dependent signaling pathways in inha(m1/m1) animals affects the proliferative activity of the stem cell and its immediate descendents. This finding may have therapeutic significance.
Activin Receptors↗
Biological monitoring of metabolites of sarin and its by-products in human urine samples.
More than 20,000 passengers of Tokyo underground trains were intoxicated with warfare toxic chemicals. Most of the patients examined had marked miosis and decreased serum cholinesterase activity. Transient increase of serum CPK activity after 3 days of the exposure was the another sign. We intensively analyzed the metabolites in the urine of 4 patients. The following analytic results indicated the exposure to sarin as well as contaminated compounds such as diisopropyl methylphosphonate (DIMP), ethyl methylphosphonate fluoridate (EMPF, or ethylsarin), diethyl methylphosphonate (DEMP), and ethyl isopropyl methylphosphonate (EIMP). (1) Isopropanol (IPA) and ethanol (EtOH) were detected of large quantities in the urine samples, and were thought to be derived from sarin and the sarin counterpart, EMPF, DIMP, DEMP and EIMP. (2) Monoalkyl methylphosphonic acids (isopropyl methylphosphonic acid (IMPA) and ethyl methylphosphonic acid (EMPA) also were excreted in large amounts with taking the similar excretion pattern of IPA and EtOH. (3) The metabolite only derived from sarin and ethylsarin is F anions whose integral output in the urine was less than the equimolar level of the excreted (IMPA + EMPA + IPA + EtOH). (4) Other corroborative findings were low lethality: of more than 5,510 patients treated, 11 were acutely dead. (5) Nine exposed males had higher sister chromatid exchange (SCE) rate (5.00 +/- 1.48/cell) than the control (3.81 +/- 0.697/cell), because dialkyl methylphosphonates seemed to have alkylating activity and producing DNA adducts. The SCE rate also increased after the in vitro exposure of lymphocytes to dialkyl methylphosphonates.
Chemical Warfare Agents↗
Effect of propranolol and IFN-beta on the induction of MHC class II expression and cytokine production by IFN-gamma IN THP-1 human monocytic cells.
This study was undertaken to investigate the effects of propranolol, IFN-beta, and the protein kinase modulators on IFN-gamma induction of MHC class II antigen expression and cytokine production in THP-1 human monocytic cells. IFN-gamma induced expression of HLA-DR and DQ molecules and secretion of the monokines IL-1 beta and TNF-alpha in THP-1 cells in a time and dose-dependent manner. The effect of INF-gamma on class II HLA antigens was dose-dependently inhibited by IFN-beta. H-7, phloretin, staurosporine as well as GF 109203X are selective enzyme inhibitors of protein kinase C (PKC), down-regulating IFN-gamma induced MHC class II expression and cytokine production. Stimulators of PKC, like PMA, replaced IFN-gamma in the induction of monokines in THP-1 cells, whereas the addition of HA 1004 or arachidonic acid to the culture had no effect on IFN-gamma mediated changes. Blocking of phospholipase D (PLD)-derived diacylglycerol (DAG) formation by propranolol abrogated IFN-gamma increased HLA class II expression and IL-1 beta secretion, but had little effect on IFN-gamma induced TNF-alpha production. These findings appear to suggest that PLD-derived phosphatidate is not the primary source of DAG production in IFN-gamma-induced TNF-alpha secretion, but may be necessary for IFN-gamma-mediated MHC class II induction and IL-1 beta production in human monocytes, whereas phospholipase A2 may not be required for IFN-gamma activation of PKC in the process.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Cloning and characterization of a family of cDNAs from human histiocyte macrophage cells encoding an arginine-rich basic protein related to the 70 kD U1-snRNP splicing factor.
This paper describes the cloning and characterization of five cDNA members of a novel family of mRNAs, termed hm-1, isolated from human U937 macrophage cells. Two family members (clones 46 and 11) show complete mRNA features [including ribosome binding sites (RBS), polyadenylation signals, and poly(A) tails], and encode the same protein (designated HM-1), but differ substantially in their 5' untranslated regions. The three other cDNAs (clones 20, 60, and 38) appear to represent partial cDNAs. The protein sequences deduced from the five hm-1 cDNAs are identical (some truncated), except for one Trp --> Cys substitution. Full-length HM-1 is 246 amino acids long, has a predicted MW of 29431, is rich in arginine residues, has a pI of 10.25, and a mean hydrophobicity index of -1.23. HM-1 contains no obvious hydrophobic N-terminal cleavable signal sequence, and no potential N-glycosylation sites, but does contain three highly conserved motifs present in U1-70K splicing factors, and contains numerous C-terminal Arg/Asp and Arg/Glu dipeptides characteristic of "RD" family members that function as regulators of mRNA splicing. Northern hybridizations indicate that hm-1 is a family of mRNAs differentially expressed in a variety of human tissues.
Amino Acid Sequence↗
Vertical transmission of human immunodeficiency virus type 1: frequency and correlation of transmission (review).
Child bearing age women constitute the fastest growing subset of the human immunodeficiency virus (HIV) infected population. Consistent with this fact is the increasing number of HIV infected children. Vertical transmission from mother to child is the most common route of infection. Because of the nature of the virus, it is difficult to determine the timing of infection. There are three time periods during which infection can occur: prenatally, perinatally, or postnatally. Evidence for each is presented within this review.
Breast Feeding↗
Regulation of apoptosis during development: input from the extracellular matrix (review).
Programmed cell death or apoptosis is an important aspect in organogenesis and tissue remodeling during development. Extensive investigations have led to the identification of many genes that participate in the regulation of cell death execution. These include the caspases and nucleases, which are involved in the degradation of cellular proteins and nuclear DNA to initiate the irreversible death process. In addition, several families of proteins like Bcl-2 superfamily can either prevent or promote cell death. The function of these proteins are getting to be understood. On the other hand, how these proteins are regulated remains to be investigated. This is in part due to the presence of diverse upstream signals that can influence cell fate. One such signal is the remodeling of the extracellular matrix (ECM), which is largely due to the action of matrix metalloproteinases (MMPs). The regulation of MMPs and ECM remodeling has been shown to affect apoptosis in different systems, including the apoptotic remodeling of the intestine during Xenopus laevis metamorphosis and post-lactation involution of the mouse mammary gland. Current evidence suggests that ECM regulates cell fate at least in part through its membrane receptors, the integrins, which in turn send the signal through yet poorly understood pathways to the nucleus to regulate gene expression.
Animals↗
Infection with the human immunodeficiency virus type 2: epidemiology and transmission (Review).
Human immunodeficiency virus type 2 (HIV-2) is known to be one of the agents that causes acquired immunodeficiency syndrome (AIDS). It has been present in West Africa since the 1960s and is currently epidemic there. Compared with human immunodeficiency virus type 1 (HIV-1), HIV-2 is genomically different. Furthermore, it is less prevalent worldwide than HIV-1. In West Africa, seropositive rates of HIV-2 are higher in urban versus rural communities, however, there are no gender differences. Sexual contact and vertical transmission are known modes of infectivity, though HIV-2 is less contagious than HIV-1.
Africa↗
Cisplatin and phorbol ester independently induce ERCC-1 protein in human ovarian carcinoma cells.
Nucleotide excision repair (NER) is the DNA repair pathway by which cisplatin-induced damage is removed from DNA in human cells. ERCC-1 is one of the essential proteins in NER, and is essential for life. Enhanced ERCC-1 expression has been associated with clinical and cellular resistance to cisplatin. We therefore carried out this study to investigate the effect of cisplatin on ERCC-1 protein expression in A2780/CP70 human ovarian cancer cells. Western blot analysis showed that ERCC-1 protein levels were increased to more than 3 times control after a 1 h cisplatin exposure to A2780/CP70 cells in culture. This increase was time- and concentration-dependent. The effect of cisplatin was maximal at 40 mM and peaked 24-48 h after exposure to the drug. These results extend our previous observations that ERCC-1 mRNA expression is induced by cisplatin in this system. TPA, a known AP-1 activator and tumor-promoting phorbol ester, also induced ERCC-1 protein to the same extent as cisplatin, but did not synergize with cisplatin in this regard. These findings suggest that ERCC-1 gene up-regulation in these cells can result through a DNA damage-response pathway, or through the induction of AP-1 activity, independent of the occurrence of DNA damage.
Antineoplastic Agents↗
Factors relating to neurotoxicity of artemisinin antimalarial drugs "listening to arteether".
The discovery of the occult brainstem neurotoxicity subsequent to widespread deployment of artemisinin derivatives has created particular problems. That is, the clinical setting for artemisinin use is problematic for accomplishing what ordinarily would be addressed in phase I-II clinical trials. Nevertheless, it is clear that an urgent and vital need exists for the deployment and widespread availability of artemisinins. The work done to date has already yielded a substantial body of evidence that, while incomplete, provides guidelines for artemisinin use to minimize the risk of these drugs while preserving their much-needed efficacy. The evidence thus far shows that route of administration, oil/water solubility and concentration-duration of drug level, are critical determinants of toxicity and can be given appropriate consideration in the clinical decisions regarding route, choice of drug used, and drug regimens. In this regard, an oral, water-soluble drug with moderately rapid clearance may be the most attractive choice in the absence of significant differences in efficacy. The same body of evidence clearly shows that toxicity can, and does, develop with no obvious or useful clinical marker. Therefore, the development and validation of a test that can reliably detect the onset of injury, at a reversible stage, is a critical path task for any future development in this class. More complete understanding of mechanisms, kinetics, and molecular targets of neurotoxicity, will certainly be forthcoming. A continuing, more generalized use of these drugs, however, cannot be fully endorsed without a useful, practical clinical test of toxicity. The requirement is especially critical in light of the reality that those patients receiving artemisinin derivatives live in high risk environments and are likely to receive repeated courses of therapy with little likelihood of close, post marketing surveillance.
Administration, Oral↗
Pharmacokinetics and pharmacodynamics of qinghaosu derivatives: how do they impact on the choice of drug and the dosage regimens?
The critical decisions of which artemisinin derivative(s) to use and by which route(s) of administration for falciparum malaria are complex scientifically and politically. Despite the need for additional pharmacokinetic, pharmacodynamic and toxicokinetic data, these drugs are too important to delay concise, rational recommendations any longer. These types of decisions must be made now, implemented on a multinational level with WHO leadership, and revised as new findings emerge. For acute, uncomplicated disease, per os dosing of artesunate or artemether for three days is recommended, but only in combination with other antimalarial drugs like mefloquine. For severe falciparum malaria, intravenous administration is the preferred route, yet current formulations for intravenous dosing are not optimal and should be an area for future development emphasis. Clearly intramuscular administration of artemether has proven effective for severe disease, yet dosing regimens shouldn't be designed with ultimate parasitological cure as the aim and the problem of bioavailability of the sesame oil formulations must be examined further. Once the life-saving reduction in parasitemia and pathophysiological sequelae have been achieved, the patient can be given oral medication to affect radical cure. Much more data will be required to define the role of per rectum dosing for the treatment of severe malaria, yet this approach holds great promise as a life-saving intervention in rural areas where this disease has it most dramatic impact.
Administration, Oral↗
Relationship between angiotensin I converting enzyme gene polymorphism and diabetic nephropathy.
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Diabetes Mellitus, Type 2↗
Analysis of the characteristics of folate binding proteins and its relationship with expression of multidrug resistance P-glycoprotein in myelodysplastic syndromes.
OBJECTIVE: To observe the characteristics of folate binding proteins (FBP) in myelodysplastic syndromes (MDS) and leukemia and to study the clinical significance of reduced folate carrier (RFC) present in MDS and its relationship with multidrug resistance (MDR). METHODS: The features of FBP on bone marrow cells were analyzed using radiolabeled 3H-folic acid (3H-FA) binding membrane proteins and SDS-polyacrylamide gel electrophoresis (SDS-PAGE). In the same time, P-glucoprotein and mRNA of MDR gene were detected using immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR) respectively in patients with MDS and leukemia. RESULTS: Two kinds of FBP, folate receptor (FR) and reduced folate carrier (RFC), were found on the leukemic cells. The same results were presented on mononuclear cells of bone marrow in 5 out of 14 MDS patients, and MDR positive was seen in 4 patiens of them. In normal control and other 9 cases of MDS FRs were only found on the mononuclear cells of bone marrow. CONCLUSION: Reduced folate carrier, which is present in the leukemic cell, is a product of neoplastic cell. It might reveal preleukmic state and have the same significance with MDR that RFC is found in MDS patients.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
[Arterialization of the great saphenous vein for treating severe ischemia of lower limbs].
This study was to observe the result in patients suffering from severe ischemia of legs with arterialization of the great saphenous vein. Eighty nine patients suffering from the disease were treated by bridging the autogenous cephalic vein or Gore-Tex artificial vessel between the great saphenous vein and the femoral or external iliac arteries. The results showed that the blood supply of the affected legs was increased immediately after operation. The ulcers of the toes and the plantar areas were healed gradually and the pain relieved. It was concluded that this method did not interfere with the reflux of the venous blood in the diseased limbs. This method was simple, safe and effective for treating severe ischemia of the lower limbs.
Adolescent↗