Search PubMed⌕ Search

Biomedical subjects

J Liu

Publications and source records attributed to J Liu.

At least 451 records · Page 25Linked to original sources
PubMed2001

PDGF-BB-mediated activation of p42(MAPK) is independent of PDGF beta-receptor tyrosine phosphorylation.

Herein, we investigated the activity of mitogen-activated protein kinase (MAPK), a key component of downstream signaling events, which is activated subsequent to platelet-derived growth factor (PDGF)-BB stimulation. Specifically, p42(MAPK) activity peaked 60 min after addition of PDGF-BB, declined thereafter, and was determined not to be a direct or necessary component of glycosaminoglycan (GAG) synthesis. PDGF-BB also activated MAPK kinase 2 (MAPKK2) but had no effect on MAPKK1 and Raf-1 activity. Chemical inhibition of Janus kinase, phosphatidylinositol 3-kinase, Src kinase, or tyrosine phosphorylation inhibition of the PDGF beta-receptor (PDGFR-beta) did not abrogate PDGF-BB-induced p42(MAPK) activation or its threonine or tyrosine phosphorylation. A dominant negative cytoplasmic receptor for hyaluronan-mediated motility variant 4 (RHAMMv4), a regulator of MAPKK-MAPK interaction and activation, did not inhibit PDGF-BB-induced p42(MAPK) activation nor did a construct expressing PDGFR-beta with cytoplasmic tyrosines mutated to phenylalanine. However, overexpression of a dominant negative PDGFR-beta lacking the cytoplasmic signaling domain abrogated p42(MAPK) activity. These results suggest that PDGF-BB-mediated activation of p42(MAPK) requires the PDGFR-beta but is independent of its tyrosine phosphorylation.

Animals↗
PubMed2001

Impaired inhibitory G-protein function contributes to increased calcium currents in rats with diabetic neuropathy.

There is a growing body of evidence that sensory neuropathy in diabetes is associated with abnormal calcium signaling in dorsal root ganglion (DRG) neurons. Enhanced influx of calcium via multiple high-threshold calcium currents is present in sensory neurons of several models of diabetes mellitus, including the spontaneously diabetic BioBred/Worchester (BB/W) rat and the chemical streptozotocin (STZ)-induced rat. We believe that abnormal calcium signaling in diabetes has pathologic significance as elevation of calcium influx and cytosolic calcium release has been implicated in other neurodegenerative conditions characterized by neuronal dysfunction and death. Using electrophysiologic and pharmacologic techniques, the present study provides evidence that significant impairment of G-protein-coupled modulation of calcium channel function may underlie the enhanced calcium entry in diabetes. N- and P-type voltage-activated, high-threshold calcium channels in DRGs are coupled to mu opiate receptors via inhibitory G(o)-type G proteins. The responsiveness of this receptor coupled model was tested in dorsal root ganglion (DRG) neurons from spontaneously-diabetic BB/W rats, and streptozotocin-induced (STZ) diabetic rats. Intracellular dialysis with GTPgammaS decreased calcium current amplitude in diabetic BB/W DRG neurons compared with those of age-matched, nondiabetic controls, suggesting that inhibitory G-protein activity was diminished in diabetes, resulting in larger calcium currents. Facilitation of calcium current density (I(DCa)) by large-amplitude depolarizing prepulses (proposed to transiently inactivate G proteins), was significantly less effective in neurons from BB/W and STZ-induced diabetic DRGs. Facilitation was enhanced by intracellular dialysis with GTPgammaS, decreased by pertussis toxin, and abolished by GDPbetaS within 5 min. Direct measurement of GTPase activity using opiate-mediated GTPgamma[(35)S] binding, confirmed that G-protein activity was significantly diminished in STZ-induced diabetic neurons compared with age-matched nondiabetic controls. Diabetes did not alter the level of expression of mu opiate receptors and G-protein alpha subunits. These studies indicate that impaired regulation of calcium channels by G proteins is an important mechanism contributing to enhanced calcium influx in diabetes.

Analgesics, Opioid↗
PubMed2001

Surgery for pediatric subglottic stenosis: disease-specific outcomes.

To set the foundation to develop a disease-based, operation-specific model to predict the outcome of pediatric airway reconstruction surgery, we performed a retrospective database review of children operated on at a single, tertiary-care children's hospital. Over the 12-year period 1988 to 2000, a total of 1,296 airway reconstruction procedures were performed. Out of these, charts were identified for 199 children who underwent laryngotracheal reconstruction for a sole diagnosis of subglottic stenosis. Children were excluded from the study if their disorder included supraglottic, glottic, or upper tracheal disease. The main outcome measures were Myer-Cotton grade-specific decannulation and extubation rates, including both operation-specific and overall results. There were 101 children who underwent double-stage laryngotracheal reconstruction. The operation-specific decannulation rates for Myer-Cotton grades 2, 3, and 4 were 85% (18/21), 37% (23/61), and 50% (7/14) (chi2 analysis, p = .0007). The overall decannulation rates were 95% (20/21), 74% (45/61), and 86% (12/14) (chi2 analysis, p = .04). There were 98 children who underwent single-stage laryngotracheal reconstruction. The operation-specific extubation rates for Myer-Cotton grades 2, 3, and 4 were 82% (37/45), 79% (34/43), and 67% (2/3) (chi2 analysis, p = .63). The overall extubation rates were 100% (45/45), 86% (37/43), and 100% (3/3) (chi2 analysis, p = .03). Logistic regression analysis showed no effect of age (less than or greater than 2 years of age) on operation-specific or overall outcome parameters. We conclude that laryngotracheal reconstruction for pediatric subglottic stenosis remains a challenging set of procedures in which multiple operations may be required to achieve eventual extubation or decannulation. Children with Myer-Cotton grade 3 or 4 disease continue to represent a significant challenge, and refinements of techniques are being examined to address this subset of children. Disease-based, operation-specific outcome statistics are the first step in the development of a meaningful predictive model.

Adolescent↗
PubMed2001

Effects of heat treatments on mechanical strength of laser-welded equi-atomic AuCu-6at%Ga alloy.

There is little information available on the mechanical strengthening of laser-welded gold alloys to achieve reliable dental prostheses. This study examined the hypothesis that heat treatments increase the mechanical strength of a laser-welded equi-atomic AuCu-6at%Ga alloy with age "hardenability" at intra-oral temperature. Cut cast gold alloy plates were laser-welded. The specimens were given one of three heat treatments: (1) solution treatment, (2) high-temperature aging after solution treatment, and (3) simulated intra-oral aging after solution treatment. As-cast and uncut specimens were also prepared. Tensile testing was conducted, and the breaking stress and yield strength were recorded. The yield strength values of all the heat-treated specimens nearly reached the values of the corresponding heat-treated control specimens. The results of this study indicated that, for high mechanical strength to be achieved, the laser-welded alloy tested should be aged at a high temperature or be intraorally aged after being laser-welded.

Dental Soldering↗
PubMed2001

Use of desmopressin and erythropoietin in an anaemic Jehovah's Witness patient with severely impaired coagulation capacity undergoing stentless aortic valve replacement.

Cardiac surgery in Jehovah's Witness patients remains a challenge in the presence of concomitant congenital or acquired coagulation disorders and anaemia. We report a case of a 66-year-old female Jehovah's Witness suffering from severe calcified aortic valve stenosis requiring aortic valve replacement. The anaemic patient suffered from concomitant platelet dysfunction and deficiency of factors V and VII due to gammopathy of immunoglobulin G. The patient was preoperatively treated with recombinant erythropoietin in combination with folic acid and iron, which resulted in an increase of the haematocrit from 0.335 to 0.416 after 22 days of treatment. Haemostasis was improved by high dose aprotinin and additional desmopressin, which could be demonstrated to be effective by a preoperative test. The patients intra- and postoperative course was uneventful, her total chest tube loss was 130 ml, and she was able to be discharged without the need of any blood transfusions. The beneficial properties of erythropoietin and desmopressin in Jehovah's Witness patients are discussed.

Aged↗
PubMed2001

The effects of maternal depression on fetal heart rate response to vibroacoustic stimulation.

To better understand the effects of untreated maternal depression on the fetus, this study examined fetal heart rate (FHR) and FHR reactivity to vibroacoustic stimulation in pregnant women with untreated depression. The 20 participants were 32- to 36-week pregnant women divided into groups with depression (N = 10) and without depression (N = 10) based on the Beck Depression Inventory (BDI; Beck, 1977; Beck & Steer, 1987). Participants were attached to a fetal heart monitor, and 10 min of baseline FHR were recorded. A vibroacoustic stimulus (VAS) was presented, and an additional 10 min of FHR were recorded. Fetuses of mothers with depression had an elevated baseline FHR and a 3.5-fold delay in return to baseline FHR after VAS presentation. Additionally, mothers with depression had significantly higher anxiety levels and took fewer prenatal vitamins during pregnancy. Delayed habituation of FHR in the fetuses of mothers with depression may be due to alterations in the internal hormonal environment and could have implications for postnatal information processing.

Acoustic Stimulation↗
PubMed2001

Endocrine manifestations of stimulatory G protein alpha-subunit mutations and the role of genomic imprinting.

The heterotrimeric G protein G(s) couples hormone receptors (as well as other receptors) to the effector enzyme adenylyl cyclase and is therefore required for hormone-stimulated intracellular cAMP generation. Receptors activate G(s) by promoting exchange of GTP for GDP on the G(s) alpha-subunit (G(s)alpha) while an intrinsic GTPase activity of G(s)alpha that hydrolyzes bound GTP to GDP leads to deactivation. Mutations of specific G(s)alpha residues (Arg(201) or Gln(227)) that are critical for the GTPase reaction lead to constitutive activation of G(s)-coupled signaling pathways, and such somatic mutations are found in endocrine tumors, fibrous dysplasia of bone, and the McCune-Albright syndrome. Conversely, heterozygous loss-of-function mutations may lead to Albright hereditary osteodystrophy (AHO), a disease characterized by short stature, obesity, brachydactyly, sc ossifications, and mental deficits. Similar mutations are also associated with progressive osseous heteroplasia. Interestingly, paternal transmission of GNAS1 mutations leads to the AHO phenotype alone (pseudopseudohypoparathyroidism), while maternal transmission leads to AHO plus resistance to several hormones (e.g., PTH, TSH) that activate G(s) in their target tissues (pseudohypoparathyroidism type IA). Studies in G(s)alpha knockout mice demonstrate that G(s)alpha is imprinted in a tissue-specific manner, being expressed primarily from the maternal allele in some tissues (e.g., renal proximal tubule, the major site of renal PTH action), while being biallelically expressed in most other tissues. Disrupting mutations in the maternal allele lead to loss of G(s)alpha expression in proximal tubules and therefore loss of PTH action in the kidney, while mutations in the paternal allele have little effect on G(s)alpha expression or PTH action. G(s)alpha has recently been shown to be also imprinted in human pituitary glands. The G(s)alpha gene GNAS1 (as well as its murine ortholog Gnas) has at least four alternative promoters and first exons, leading to the production of alternative gene products including G(s)alpha, XLalphas (a novel G(s)alpha isoform that is expressed only from the paternal allele), and NESP55 (a chromogranin-like protein that is expressed only from the maternal allele). A fourth alternative promoter and first exon (exon 1A) located approximately 2.5 kb upstream of the G(s)alpha promoter is normally methylated on the maternal allele and transcriptionally active on the paternal allele. In patients with isolated renal resistance to PTH (pseudohypoparathyroidism type IB), the exon 1A promoter region has a paternal-specific imprinting pattern on both alleles (unmethylated, transcriptionally active), suggesting that this region is critical for the tissue-specific imprinting of G(s)alpha. The GNAS1 imprinting defect in pseudohypoparathyroidism type IB is predicted to decrease G(s)alpha expression in renal proximal tubules. Studies in G(s)alpha knockout mice also demonstrate that this gene is critical in the regulation of lipid and glucose metabolism.

Animals↗
PubMed2001

Requirement of Sp1 and estrogen receptor alpha interaction in 17beta-estradiol-mediated transcriptional activation of the low density lipoprotein receptor gene expression.

Estrogen is one of the most important physiological regulators of low density lipoprotein receptor (LDLR) expression. Despite many studies conducted in animals and humans showing increased expressions of LDLR messenger RNA by hormone treatment, the molecular basis of the effect of estrogen on LDLR transcription has not been clearly elucidated. By using HepG2 cells that transiently express functional estrogen receptor alpha (ERalpha) and LDLR promoter constructs, we show that the specific interaction of ERalpha with the transcription factor Sp1 bound to the LDLR promoter is responsible for the activation of LDLR transcription by estrogen. We demonstrate that 1) mutations to abrogate the binding of Sp1 to its recognition sequences present in repeat 1 and repeat 3 elements of the LDLR promoter completely abolish the ERalpha-mediated activation of the LDLR promoter activity; 2) mutations that abolish the selective DNA-binding activity or inactivate the C-terminal transcription activation function (AF2) of ERalpha had no effect on the ability of ERalpha to activate LDLR transcription; however, transcriptional activation was completely lost by deletion of the N-terminal transcription activation region (AF1); 3) a subregion of AF1 (amino acids 67-139) was further identified to be important for ERalpha to activate the LDLR promoter; and 4) ERalpha enhanced the formation of Sp1-repeat 3 DNA complexes. We also show that mutation at the sterol-responsive element-1 site diminishes the activity of ERalpha on LDLR transcription, thereby suggesting that the sterol-responsive element-1-binding protein may interact with the Sp1-ERalpha complex to trans-activate LDLR gene transcription. This study for the first time provides a molecular basis for an understanding of the regulation of LDLR transcription by estrogens.

Cell Nucleus↗
PubMed2001

Inhibin/activin betaB-subunit expression in pheochromocytomas favors benign diagnosis.

Malignancy of pheochromocytomas is difficult to estimate on the basis of histopathological features. Good prognostic markers are not available. In our search for new markers to differentiate malignant pheochromocytomas from benign ones we tested the value of inhibin/activin subunit expression. Inhibins are heterodimeric glycoproteins consisting of an alpha-subunit and either a betaA- or a betaB-subunit. Activins are composed of beta-subunits only. Immunohistochemically inhibin/activin betaB-subunit was strongly positive in the normal adrenal medulla, but the cortex was negative. A striking difference was found in inhibin/activin betaB expression between benign and malignant pheochromocytomas. The majority of benign adrenal tumors (27 of 30) showed strong or moderate immunoreactivity, whereas all seven malignant tumors were negative or only weakly positive for inhibin/activin betaB-subunit. The percentage of positively staining cells varied greatly in extraadrenal pheochromocytomas and in those benign tumors that showed over 5 mitoses/10 high power fields, necrosis, or capsular or vascular invasion, here called borderline tumors. Inhibin/activin betaB messenger ribonucleic acid was also found in pheochromocytomas. However, no significant differences in messenger ribonucleic acid levels were found in various types of tumors. Weak immunohistochemical positivity for inhibin/activin betaA-subunit was detected in the adrenal cortex, but the medulla and most of the pheochromocytomas were negative. Our data show that inhibin/activin betaB-subunit is expressed in normal adrenal medullary cells. Strong staining is found in most benign adrenal pheochromocytomas, whereas malignant tumors are almost negative. This suggests that loss of inhibin/activin betaB-subunit expression in pheochromocytomas may be used as an indicator of malignant potential.

Activins↗
PubMed2001

The furry gene of Drosophila is important for maintaining the integrity of cellular extensions during morphogenesis.

The Drosophila imaginal cells that produce epidermal hairs, the shafts of sensory bristles and the lateral extensions of the arista are attractive model systems for studying the morphogenesis of polarized cell extensions. We now report the identification and characterization of furry, an essential Drosophila gene that is involved in maintaining the integrity of these cellular extensions during morphogenesis. Mutations in furry result in the formation of branched arista laterals, branched bristles and a strong multiple hair cell phenotype that consists of clusters of epidermal hairs and branched hairs. By following the morphogenesis of arista laterals in pupae, we have determined that the branched laterals are due to the splitting of individual laterals during elongation. In genetic mosaics furry was found to act cell autonomously in the wing. The phenotypes of double mutant cells argue that furry functions independently of the frizzled planar polarity pathway and that it probably functions in the same pathway as the tricornered gene. We used a P-element insertion allele as a tag to clone the furry gene and found it to be a large and complicated gene that encodes a pair of large conserved proteins of unknown biochemical function.

Amino Acid Sequence↗
PubMed2001

Rigorous electromagnetic analysis of a microcylindrical axilens with long focal depth and high transverse resolution.

We first present nonparaxial designs for a microcylindrical axilens with different long focal depths and rigorously analyze electromagnetic field distributions of the axilens using integral equations and the boundary-element method. Numerical results show that the designed axilenses indeed have the special feature of attaining a long focal depth while keeping high transverse resolution for numerical apertures of 2.4, 2.0, and 1.0. The ratio between the extended focal depth of the designed axilens and the focal depth of the conventional focal lens is 1.41, the corresponding maximal extended focal depth of the axilens can reach 28 microm, and the spot size of the focal beam is approximately 10 microm over the focal range.

Journal Article↗
PubMed2001

Initial evidence of endothelial cell apoptosis as a mechanism of systemic capillary leak syndrome.

BACKGROUND: Systemic capillary leak syndrome (SCLS) is a rare disorder of unknown etiology that is characterized by acute recurrent attacks of hypovolemic shock commonly following an inflammatory stimulus such as a viral illness. Prophylactic therapy is generally ineffective, and the outcome is frequently fatal. METHODS: In order to investigate the cellular mechanisms leading to SCLS, we examined the effects of sera from two patients with active SCLS on microvascular endothelial cell apoptosis in vitro. Apoptosis was determined by morphologic criteria, DNA fragmentation, annexin V stain, and by a quantitative photometric assay. The apoptotic pathway was investigated by Western blot of endothelial cells lysate after exposure to SCLS sera. RESULTS: The sera from patients with active SCLS mediated profound apoptosis of microvascular endothelial cells shortly after exposure. The exposed microvascular endothelial cells underwent immediate apoptosis as evidenced by morphologic changes, plasma membrane phosphatidylserine exposure, and by DNA fragmentation. Increased Bax/Bcl-2 ratio in endothelial cells exposed to SCLS sera was observed and suggested an oxidation injury as the possible mechanism for endothelial apoptosis. This potential mechanism was further explored by measuring intracellular reactive oxygen species (ROS) following SCLS serum exposure. Sera from both patients caused marked increases in ROS, initially detectable at 1 h and persisted for at least 12 h, with control serum from healthy subjects showing no effect on basal endothelial cell ROS concentrations. CONCLUSION: Components from the sera of patients with active systemic capillary leak syndrome in contrast to healthy subject sera mediate early and extensive endothelial apoptosis in vitro that is associated with oxidation injury. These data represent compelling initial evidence for oxidation-induced apoptosis as a likely mechanism for endothelial injury leading to SCLS.

Apoptosis↗
PubMed2001

Isolation of a novel collagen gene (Mj-col-5) in Meloidogyne javanica and analysis of its expression pattern.

Mj-col-5, isolated from the plant parasitic nematode Meloidogyne javanica, has a longer carboxy-terminus than other members of the Caenorhabditis elegans COL-6 subfamily of cuticle collagen, including an extra tyrosine residue, and may form altered nonreducible cross-linkages. By semiquantitative determination at different life stages, Mj-col-5 transcript was shown to be more abundant in eggs than in juveniles/young females and adult females. To characterize further this gene's contribution to the changing cuticle of the nematode, we expressed a fusion protein containing a nonconserved 58-amino-acid sequence from the putative Mj-col-5 gene product and raised rabbit antiserum against the fusion protein. The antiserum detected a strongly reacting band (36 kDa, designated MJE36) on western blots of M. javanica eggs extracted with beta-mercaptoethanol. MJE36 was sensitive to collagenase and was not detected on western blots of extracts from M. javanica second-stage juveniles or adult females. A band of the same molecular size was detected in Meloidogyne incognita egg extracts but not in those of Heterodera avenae. Immunoblot indicated that MJE36 is not present in egg shells of M. javanica.

Amino Acid Sequence↗
PubMed2001

Comprehensive-trace level determination of methyltin compounds in aqueous samples by cryogenic purge-and-trap gas chromatography with flame photometric detection.

A comprehensive method was developed for the sensitive and fast determination of trace levels of methyltin compounds in aqueous samples. Tin compounds in aqueous solution at pH 5 were converted to the corresponding volatile hydrides: CH3SnH3, (CH3)2SnH2, and (CH3)3SnH, by reaction with potassium borohydride. A CP-4010 purge and trap injector (PTI) was used to purge analyte species from water directly. The volatile derivatives were base-line separated on a capillary column in an Angilent-6890 gas chromatograph by a suitable temperature program and were detected by a flame photometric detector (FPD). The detection limits were 18 ng L-1 for monomethyltin, 12 ng L-1 for dimethyltin, and 3 ng L-1 for trimethyltin, respectively. This method was successfully applied to the determination of methyltin compounds in different aqueous samples.

Chemical Industry↗
PubMed2001

Parameters important in fabricating enzyme electrodes using self-assembled monolayers of alkanethiols.

The fabrication of enzyme electrodes using self-assembled monolayers (SAMs) has attracted considerable interest because of the spatial control over the enzyme immobilization. A model system of glucose oxidase covalently bound to a gold electrode modified with a SAM of 3-mercaptopropionic acid was investigated with regard to the effect of fabrication variables such as the surface topography of the underlying gold electrode, the conditions during covalent attachment of the enzyme and the buffer used. The resultant monolayer enzyme electrodes have excellent sensitivity and dynamic range which can easily be adjusted by controlling the amount of enzyme immobilized. The major drawback of such electrodes is the response which is limited by the kinetics of the enzyme rather than mass transport of substrates. Approaches to bringing such enzyme electrodes into the mass transport limiting regime by exploiting direct electron transfer between the enzyme and the electrode are outlined.

Biosensing Techniques↗
PubMed2001

1,3-beta-Glucan synthase: a useful target for antifungal drugs.

1,3-beta-glucan synthase, a multisubunit enzyme, is responsible for fungal cell wall construction, division septum deposition, and ascospore wall assembly. The catalytic subunit of this enzyme complex, an integral membrane protein, has been identified both in model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, and in pathogenic fungi such as Candida, Aspergillus, Cryptococcus and Pneumocystis species. The catalytic activity of the 1,3-beta-glucan synthase is regulated by a small GTPase of the Ras superfamily, the Rho-GTPase, and protein kinase C (Pkc)-like signaling molecules. It has been shown that the plasma membrane localization of this enzyme is essential for its activity. Interestingly, inhibition of 1,3-beta-glucan synthase activity by anti-fungal drugs of the lipopeptide type triggers a cell cycle feedback mechanism leading to cell cycle arrest. Recent progress in studies of molecular mechanisms of the temporal and spatial regulation of 1,3-beta-glucan synthase is presented. The implication of the cell cycle checkpoint that is activated by the anti-fungal drugs is also discussed.

Antifungal Agents↗
PubMed2001

Developing a prediction rule from automated clinical databases to identify high-risk patients in a large population with diabetes.

OBJECTIVE: To develop and validate a prediction rule for identifying diabetic patients at high short-term risk of complications using automated data in a large managed care organization. RESEARCH DESIGN AND METHODS: Retrospective cohort analyses were performed in 57,722 diabetic members of Kaiser Permanente, Northern California, aged > or =19 years. Data from 1994 to 1995 were used to model risk for macro- and microvascular complications (n = 3,977), infectious complications (n = 1,580), and metabolic complications (n = 316) during 1996. Candidate predictors (n = 36) included prior inpatient and outpatient diagnoses, laboratory records, pharmacy records, utilization records, and survey data. Using split-sample validation, the risk scores derived from logistic regression models in half of the population were evaluated in the second half. Sensitivity, positive predictive value, and receiver operating characteristics curves were used to compare scores obtained from full models to those derived using simpler approaches. RESULTS: History of prior complications or related outpatient diagnoses were the strongest predictors in each complications set. For patients without previous events, treatment with insulin alone, serum creatinine > or =1.3 mg/dl, use of two or more antihypertensive medications, HbA(1c) >10%, and albuminuria/microalbuminuria were independent predictors of two or all three complications. Several risk scores derived from multivariate models were more efficient than simply targeting patients with elevated HbA(1c) levels for identifying high-risk patients. CONCLUSIONS: Simple prediction rules based on automated clinical data are useful in planning care management for populations with diabetes.

Adult↗