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Biomedical subjects

H Li

Publications and source records attributed to H Li.

At least 613 records · Page 34Linked to original sources
PubMed2000

Tumor necrosis factor receptor-1 is critically involved in the development of experimental autoimmune myasthenia gravis.

Tumor necrosis factor receptor-1 (TNFR1, CD120a) has been implicated in the pathogenesis of several experimental models of T cell-mediated autoimmune disorders, but its role in antibody-mediated autoimmune diseases has not been addressed. Experimental autoimmune myasthenia gravis (EAMG), an autoantibody-mediated T cell-dependent neuromuscular disorder, represents an animal model for myasthenia gravis in human. To investigate the role of TNFR1 in the pathogenesis of EAMG, TNFR1(-/-) and wild-type mice were immunized with TORPEDO: acetylcholine receptor (AChR) in complete Freund's adjuvant. TNFR1(-/-) mice failed to develop EAMG. Lymphoid cells from TNFR1(-/-) mice produced low amounts of T(h)1 (IFN-gamma, IL-2 and IL-12)-type cytokines, but elevated levels of T(h)2 (IL-4 and IL-10)-type cytokines compared with lymphoid cells of wild-type mice. Accordingly, the levels of anti-AChR IgG2 antibodies were severely reduced and the level of anti-AChR IgG1 antibodies were moderately reduced. Co-injection of recombinant mouse IL-12 with AChR in adjuvant restored T cell responses to AChR and promoted development of EAMG in TNFR1(-/-) mice. These results demonstrate that the TNF/TNFR1 system is required for the development of EAMG. The lack of a functional TNF/TNFR1 system can, at least in part, be substituted by IL-12 at the stage of initial priming with AChR and adjuvant.

Animals↗
PubMed2000

Bisulfite-containing propofol: is it a cost-effective alternative to Diprivan for induction of anesthesia?

UNLABELLED: Propofol (Diprivan(TM); AstraZeneca, Wilmington, DE) is a commonly used drug for the induction of general anesthesia in the ambulatory setting. With the availability of a new bisulfite-containing generic formulation of propofol, questions have arisen regarding its cost effectiveness and safety compared with Diprivan(TM). Two hundred healthy outpatients were randomly assigned, according to a double-blinded protocol, to receive either Diprivan(TM) or bisulfite-containing propofol 1.5 mg/kg IV as part of a standardized induction sequence. Maintenance of anesthesia consisted of either desflurane (4%-8% end-tidal) or sevoflurane (1%-2% end-tidal) in combination with a remifentanil infusion (0.125 microg x kg(-1) x min(-1) IV). Patient assessments included pain on injection, induction time, hemodynamic and bispectral electroencephalographic changes during induction, emergence time, and incidence of postoperative nausea and vomiting. The two propofol groups were comparable demographically, and the induction times and bispectral index values during the induction were also similar. However, the bisulfite-containing formulation was associated with less severe pain on injection (5% vs 11%), with fewer patients recalling pain on injection after surgery (38% vs. 51%, P<0.05). None of the patients manifested allergic-type reactions after the induction of anesthesia. The acquisition cost (average wholesale price in US dollars) of a 20-mL ampoule of Diprivan(TM) was $15 compared with $13 for the bisulfite-containing propofol formulation. Therefore, we concluded that the bisulfite-containing formulation of propofol is a cost-effective alternative to Diprivan(TM) for the induction of outpatient anesthesia. IMPLICATIONS: Bisulfite-containing propofol and Diprivan(TM) (AstraZeneca, Wilmington, DE) were similar with respect to their induction characteristics; however, the generic formulation was associated with a smaller incidence of injection pain. Assuming that the drug costs are similar, these data suggest that the bisulfite-containing formulation of propofol is a cost-effective alternative to Diprivan(TM).

Ambulatory Care↗
PubMed2000

Comparison of the costs and recovery profiles of three anesthetic techniques for ambulatory anorectal surgery.

BACKGROUND: Given the current practice environment, it is important to determine the anesthetic technique with the highest patient acceptance and lowest associated costs. The authors compared three commonly used anesthetic techniques for anorectal procedures in the ambulatory setting. METHODS: Ninety-three consenting adult outpatients undergoing anorectal surgery were randomly assigned to one of three anesthetic treatment groups: group 1 received local infiltration with a 30-ml mixture containing 15 ml lidocaine, 2%, and 15 ml bupivacaine, 0.5%, with epinephrine (1:200,000) in combination with intravenous sedation using a propofol infusion, 25-100 microg. kg-1. min-1; group 2 received a spinal subarachnoid block with a combination of 30 mg lidocaine and 20 microg fentanyl with midazolam, 1-2-mg intravenous bolus doses; and group 3 received general anesthesia with 2.5 mg/kg propofol administered intravenously and 0.5-2% sevoflurane in combination with 65% nitrous oxide. In groups 2 and 3, the surgeon also administered 10 ml of the previously described local anesthetic mixture at the surgical site before the skin incision. RESULTS: The mean costs were significantly decreased in group 1 ($69 +/- 20 compared with $104 +/- 18 and $145 +/- 25 in groups 2 and 3, respectively) because both intraoperative and recovery costs were lowest (P < 0.05). Although the surgical time did not differ among the three groups, the anesthesia time and times to oral intake and home-readiness were significantly shorter in group 1 (vs. groups 2 and 3). There was no significant difference among the three groups with respect to the postoperative side effects or unanticipated hospitalizations. However, the need for pain medication was less in groups 1 and 2 (19% and 19% vs. 45% for group 3; P < 0.05). Patients in group 1 had no complaints of nausea (vs. 3% and 26% in groups 2 and 3, respectively). More patients in group 1 (68%) were highly satisfied with the care they received than in groups 2 (58%) and 3 (39%). CONCLUSIONS: The use of local anesthesia with sedation is the most cost-effective technique for anorectal surgery in the ambulatory setting.

Adult↗
PubMed2000

Molecular biology of arrhythmic syndromes.

In this review, the up-to-date understanding of the molecular basis of primary ventricular arrhythmias will be outlined. Two disorders have recently been well described at the molecular level, the long QT syndromes and Brugada syndrome, and in this paper we review the current scientific knowledge of each disease.

Bundle-Branch Block↗
PubMed2000

The effects of electroconvulsive therapy on melatonin.

Although several studies have investigated the impact of various antidepressant medications on melatonin, there are no published reports addressing the effects of electroconvulsive therapy (ECT). Melatonin's major urinary metabolite, 6-sulfatoxymelatonin (6MT), was measured before and after an acute course of ECT. Fourteen subjects diagnosed with major depression who had failed prior pharmacologic therapy were enrolled. 6MT excretion was measured using an enzyme-linked immunosorbent assay test in 24 hour samples separated into daytime and nighttime components. Hamilton Rating Scale for Depression scores showed a significant improvement (p < 0.0001). Data analysis using the Wilcoxon signed rank test demonstrated a significant decrease in 24 hour 6MT post-ECT (p < 0.016) and daytime 6MT (p < 0.008). These results demonstrate an association between a therapeutic response to ECT and decrease in endogenous melatonin production.

Adult↗
PubMed2000

The complete sequence of hepatitis E virus genotype 4 reveals an alternative strategy for translation of open reading frames 2 and 3.

Isolates of hepatitis E virus (HEV) have recently been described from China that are distinct from Burmese, Mexican and US viruses and constitute a novel genotype (genotype 4). Here, the complete genomic sequence of a representative isolate of genotype 4 HEV, amplified directly from the stool of an acutely infected patient, is presented. Analysis of the entire sequence confirms our previous conclusion, based upon partial sequence data, that these Chinese isolates belong to a novel genotype. Typical of genetic variation in HEV, most nucleotide substitutions occur in the third base of the codon and do not affect the amino acid sequence. The genotype 4 virus is unusual in that a single nucleotide insertion in the ORF 3 region changes the initiation of ORF 3, and perhaps also ORF 2. The consequences of these changes are discussed.

Adult↗
PubMed2000

ATMPK4, an Arabidopsis homolog of mitogen-activated protein kinase, is activated in vitro by AtMEK1 through threonine phosphorylation.

The modulation of mitogen-activated protein kinase (MAPK) activity regulates many intracellular signaling processes. In animal and yeast cells, MAP kinases are activated via phosphorylation by the dual-specificity kinase MEK (MAP kinase kinase). Several plant homologs of MEK and MAPK have been identified, but the biochemical events underlying the activation of plant MAPKs remain unknown. We describe the in vitro activation of an Arabidopsis homolog of MAP kinase, ATMPK4. ATMPK4 was phosphorylated in vitro by an Arabidopsis MEK homolog, AtMEK1. This phosphorylation occurred principally on threonine (Thr) residues and resulted in elevated ATMPK4 kinase activity. A second Arabidopsis MEK isoform, ATMAP2Kalpha, failed to phosphorylate ATMPK4 in vitro. Tyr dephosphorylation by the Arabidopsis Tyr-specific phosphatase AtPTP1 resulted in an almost complete loss of ATMPK4 activity. Immunoprecipitates of Arabidopsis extracts with anti-ATMPK4 antibodies displayed myelin basic protein kinase activity that was sensitive to treatment with AtPTP1. These results demonstrate that a plant MEK can phosphorylate and activate MAPK, and that Tyr phosphorylation is critical for the catalytic activity of MAPK in plants. Surprisingly, in contrast to the animal enzymes, AtMEK1 may not be a dual-specificity kinase but, rather, the required Tyr phosphorylation on ATMPK4 may result from autophosphorylation.

Arabidopsis↗
PubMed2000

Arabidopsis RopGAPs are a novel family of rho GTPase-activating proteins that require the Cdc42/Rac-interactive binding motif for rop-specific GTPase stimulation.

The plant-specific Rop subfamily of Rho GTPases, most closely related to the mammalian Cdc42 and Rac GTPases, plays an important role in the regulation of calcium-dependent pollen tube growth, H(2)O(2)-mediated cell death, and many other processes in plants. In a search for Rop interactors using the two-hybrid method, we identified a family of Rho GTPase-activating proteins (GAP) from Arabidopsis, termed RopGAPs. In addition to a GAP catalytic domain, RopGAPs contain a Cdc42/Rac-interactive binding (CRIB) motif known to allow Cdc42/Rac effector proteins to bind activated Cdc42/Rac. This novel combination of a GAP domain with a CRIB motif is widespread in higher plants and is unique to the regulation of the Rop GTPase. A critical role for CRIB in the regulation of in vitro RopGAP activity was demonstrated using point and deletion mutations. Both types of mutants have drastically reduced capacities to stimulate the intrinsic Rop GTPase activity and to bind Rop. Furthermore, RopGAPs preferentially stimulate the GTPase activity of Rop, but not Cdc42 in a CRIB-dependent manner. In vitro binding assays show that the RopGAP CRIB domain interacts with GTP- and GDP-bound forms of Rop, as well as the transitional state of Rop mimicked by aluminum fluoride. The CRIB domain also promotes the association of the GAP domain with the GDP-bound Rop, as does aluminum fluoride. These results reveal a novel CRIB-dependent mechanism for the regulation of the plant-specific family of Rho GAPs. We propose that the CRIB domain facilitates the formation of or enhanced GAP-mediated stabilization of the transitional state of the Rop GTPase.

Aluminum Compounds↗
PubMed2000

Sterol methyltransferase 1 controls the level of cholesterol in plants.

The side chain in plant sterols can have either a methyl or ethyl addition at carbon 24 that is absent in cholesterol. The ethyl addition is the product of two sequential methyl additions. Arabidopsis contains three genes-sterol methyltransferase 1 (SMT1), SMT2, and SMT3-homologous to yeast ERG6, which is known to encode an S-adenosylmethionine-dependent C-24 SMT that catalyzes a single methyl addition. The SMT1 polypeptide is the most similar of these Arabidopsis homologs to yeast Erg6p. Moreover, expression of Arabidopsis SMT1 in erg6 restores SMT activity to the yeast mutant. The smt1 plants have pleiotropic defects: poor growth and fertility, sensitivity of the root to calcium, and a loss of proper embryo morphogenesis. smt1 has an altered sterol content: it accumulates cholesterol and has less C-24 alkylated sterols content. Escherichia coli extracts, obtained from a strain expressing the Arabidopsis SMT1 protein, can perform both the methyl and ethyl additions to appropriate sterol substrates, although with different kinetics. The fact that smt1 null mutants still produce alkylated sterols and that SMT1 can catalyze both alkylation steps shows that there is considerable overlap in the substrate specificity of enzymes in sterol biosynthesis. The availability of the SMT1 gene and mutant should permit the manipulation of phytosterol composition, which will help elucidate the role of sterols in animal nutrition.

Amino Acid Sequence↗
PubMed2000

Crystallization and preliminary X-ray analysis of luffaculin, a ribosome-inactivating protein from sponge-gourd seeds.

Luffaculin is a ribosome-inactivating protein. Crystals suitable for X--ray diffraction were first obtained using the hanging-drop vapour-diffusion method. X-ray studies show that the crystals belong to space group C2, with unit-cell parameters a = 89.90, b = 59.82, c = 55.18 A, beta = 120.81 degrees, and have one molecule in the crystallographic asymmetric unit. The crystals diffract X-rays to at least 2.0 A resolution.

Animals↗
PubMed2000

15N and 1H NMR study of histidine containing protein (HPr) from Staphylococcus carnosus at high pressure.

The pressure-induced changes in 15N enriched HPr from Staphylococcus carnosus were investigated by two-dimensional (2D) heteronuclear NMR spectroscopy at pressures ranging from atmospheric pressure up to 200 MPa. The NMR experiments allowed the simultaneous observation of the backbone and side-chain amide protons and nitrogens. Most of the resonances shift downfield with increasing pressure indicating generalized pressure-induced conformational changes. The average pressure-induced shifts for amide protons and nitrogens are 0.285 ppm GPa(-1) at 278 K and 2.20 ppm GPa(-1), respectively. At 298 K the corresponding values are 0.275 and 2.41 ppm GPa(-1). Proton and nitrogen pressure coefficients show a significant but rather small correlation (0.31) if determined for all amide resonances. When restricting the analysis to amide groups in the beta-pleated sheet, the correlation between these coefficients is with 0.59 significantly higher. As already described for other proteins, the amide proton pressure coefficients are strongly correlated to the corresponding hydrogen bond distances, and thus are indicators for the pressure-induced changes of the hydrogen bond lengths. The nitrogen shift changes appear to sense other physical phenomena such as changes of the local backbone conformation as well. Interpretation of the pressure-induced shifts in terms of structural changes in the HPr protein suggests the following picture: the four-stranded beta-pleated sheet of HPr protein is the least compressible part of the structure showing only small pressure effects. The two long helices a and c show intermediary effects that could be explained by a higher compressibility and a concomitant bending of the helices. The largest pressure coefficients are found in the active center region around His15 and in the regulatory helix b which includes the phosphorylation site Ser46 for the HPr kinase. This suggests that this part of the structure occurs in a number of different structural states whose equilibrium populations are shifted by pressure. In contrast to the surrounding residues of the active center loop that show large pressure effects, Ile14 has a very small proton and nitrogen pressure coefficient. It could represent some kind of anchoring point of the active center loop that holds it in the right place in space, whereas other parts of the loop adapt themselves to changing external conditions.

Amides↗
PubMed2000

Structure of an analog of fusion peptide from hemagglutinin.

A 20-residue peptide E5 containing five glutamates, an analog of the fusion peptide of influenza virus hemagglutinin (HA) exhibiting fusion activity at acidic pH lower than 6.0-6.5 was studied by circular dichroism (CD), Fourier transform infrared, and 1H-NMR spectroscopy in water, water/trifluoroethanol (TFE) mixtures, dodecylphosphocholine (DPC) micelles, and phospholipid vesicles. E5 became structurally ordered at pH < or = 6 and the helical content in the peptide increased in the row: water < water/TFE < DPC approximately = phospholipid vesicle while the amount of beta-structure was approximately reverse. 1H-NMR data and line-broadening effect of 5-, 16-doxylstearates on proton resonances of DPC bound peptide showed E5 forms amphiphilic alpha-helix in residues 2-18, which is flexible in 11-18 part. The analysis of the proton chemical shifts of DPC bound and CD intensity at 220 nm of phospholipid bound E5 showed that the pH dependence of helical content is characterized by the same pKa approximately 5.6. Only Glu11 and Glu15 in DPC bound peptide showed such elevated pKas, presumably due to transient hydrogen bond(s) Glu11 (Glu15) deltaCOO- (H+)...HN Glu15 that dispose(s) the side chain of Glu11 (Glu15) residue(s) close to the micelle/water interface. These glutamates are present in the HA-fusion peptide and the experimental half-maximal pH of fusion for HA and E5 peptides is approximately 5.6. Therefore, a specific anchorage of these peptides onto membrane necessary for fusion is likely driven by the protonation of the carboxylate group of Glu11 (Glu15) residue(s) participating in transient hydrogen bond(s).

Circular Dichroism↗
PubMed2000

Patterns of parapatric speciation.

Geographic variation may ultimately lead to the splitting of a subdivided population into reproductively isolated units in spite of migration. Here, we consider how the waiting time until the first split and its location depend on different evolutionary factors including mutation, migration, random genetic drift, genetic architecture, and the geometric structure of the habitat. We perform large-scale, individual-based simulations using a simple model of reproductive isolation based on a classical view that reproductive isolation evolves as a by-product of genetic divergence. We show that rapid parapatric speciation on the time scale of a few hundred to a few thousand generations is plausible even when neighboring subpopulations exchange several individuals each generation. Divergent selection for local adaptation is not required for rapid speciation. Our results substantiates the claims that species with smaller range sizes (which are characterized by smaller local densities and reduced dispersal ability) should have higher speciation rates. If mutation rate is small, local abundances are low, or substantial genetic changes are required for reproductive isolation, then central populations should be the place where most splits take place. With high mutation rates, high local densities, or with moderate genetic changes sufficient for reproductive isolation, speciation events are expected to involve mainly peripheral populations.

Animals↗
PubMed2000

Prevalence of TT virus infection in blood donors with elevated ALT in the absence of known hepatitis markers.

OBJECTIVE: Recently a novel DNA virus (TT virus) has been identified in Japan and shown to be associated with elevated aminotransferase levels after blood transfusion. The exact role of TTV in the pathogenesis of liver disease is yet to be established. Our aim was to determine the prevalence and role of TTV in the pathogenesis of elevated transaminases in healthy blood donors in the absence of markers for viral hepatitis A-C. METHODS: Stored sera were collected from 99 healthy blood donors with elevated alanine amino transferase (ALT) values that were discovered at the time of blood donation. A total of 146 samples were obtained from healthy donors with normal ALT values who were used as controls. None of the patients or controls had a history of blood transfusion or had clinical signs of acute or chronic hepatitis. Serological markers for hepatitis A, hepatitis B, and hepatitis C viruses were negative. TTV DNA was amplified and detected using polymerase chain reaction followed by gel electrophoresis. RESULTS: Five of 99 (5%) samples obtained from donors with elevated ALT had TTV DNA detected by PCR, as compared to one of 146 (0.7%) of those with normal ALT (p = 0.006). Among those with elevated ALT, mean ALT values in patients with TTV (296 +/- 305 U/L) were higher than in patients without TTV (95 +/- 37 U/L), but the difference was not statistically significant (p = 0.08). The two samples with highest ALT values (both >450 U/L) were among the five samples with detectable TTV DNA in serum. CONCLUSIONS: Although TTV is not likely to explain the majority of elevated ALT cases in otherwise healthy blood donors, TTV infection may potentially be associated with some cases. Based on these findings, we propose that the role of TTV in the pathogenesis of acute and chronic liver diseases merits further investigation.

Alanine Transaminase↗
PubMed2000

Identification of bone morphogenetic proteins 2 and 4 in commercial demineralized freeze-dried bone allograft preparations: pilot study.

BACKGROUND: Demineralized freeze-dried bone allografts (DFDBAs) have been proposed as a useful adjunct in periodontal therapy to induce periodontal regeneration through the induction of new bone formation. The presence of bone morphogenetic proteins (BMPs) within the demineralized matrix has been proposed as a possible mechanism through which DFDBA may exert its biologic effect. However, in recent years, the predictability of results using DFDBA has been variable and has led to its use being questioned. One reason for the variability in tissue response may be attributed to differences in the processing of DFDBA, which may lead to loss of activity of any bioactive substances within the DFDBA matrix. Therefore, the purpose of this investigation was to determine whether there are detectable levels of bone morphogenetic proteins in commercial DFDBA preparations. METHODS: A single preparation of DFDBA was obtained from three commercial sources. Each preparation was studied in triplicate. Proteins within the DFDBA samples were first extracted with 4M guanidinium HCI for seven days at 40 degrees celsius and the residue was further extracted with 4M guanidinium HCL/EDTA for seven days at 40 degrees celsius. Two anti-human BMP-2 and -4 antibodies were used for the detection of the presence of BMP's in the extracts. RESULTS: Neither BMP-2 nor BMP-4 was detected in any of the extracts. When recombinant human BMP-2 and -4 were added throughout the extraction process of DFDBA extraction, not only were intact proteins detected but smaller molecular weight fragments were also noted in the extract. CONCLUSIONS: These results indicate that all of the DFDBA samples tested had no detectable amounts of BMP-2 and -4. In addition, an unknown substance present in the DFDBA may be responsible for degradation of whatever BMPs might be present.

Antibodies, Monoclonal↗
PubMed2000

Structure-activity relationship of staurosporine analogs in regulating expression of endothelial nitric-oxide synthase gene.

In human umbilical vein endothelial cells and in human umbilical vein endothelial cell-derived EA.hy 926 cells, staurosporine (Stsp) and its glycosidic indolocarbazole analogs 7-hydroxystaurosporine (UCN-01) and 4'-N-benzoyl staurosporine (CGP 41251) enhanced nitric-oxide synthase (NOS) III mRNA expression (analyzed by RNase protection assay), protein expression (determined by Western blot), and activity [measured by rat fetal lung fibroblast (RFL-6) reporter cell assay] in a concentration- and time-dependent manner. In contrast, the bisindolylmaleimide analogs GF 109203X, Ro 31-8220 and Gö 6983 had no effect on NOS III expression, and Gö 6976, a methyl- and cyanoalkyl-substituted nonglycosidic indolocarbazole derivative of Stsp, even reduced NOS III expression in a concentration-dependent fashion. The up-regulation of NOS III expression by Stsp and analogs appears to be a transcriptional event because Stsp, 7-hydroxystaurosporine, and CGP 41251 enhanced the activity of a 1.6-kb human NOS III promoter fragment transiently transfected into EA.hy 926 endothelial cells. Stsp and analogs did not affect the stability of the NOS III mRNA. Stsp is known as a potent protein kinase (PK) inhibitor. Data obtained with other kinase inhibitors (and stimulators) indicated, however, that the effect of Stsp and analogs on NOS III expression was unrelated to the activities of PKC, PKA, PKG, or tyrosine kinase(s). Stsp analogs such as CGP 41251 also counteracted the NOS III mRNA-decreasing effect of tumor necrosis factor-alpha. These findings demonstrate that Stsp analogs represent a new class of compounds positively interacting with the transcription of the endothelial NOS III gene. Such compounds may prove useful in the prophylaxis and therapy of vascular disease.

Alkaloids↗
PubMed2000

A redox-responsive regulator of photosynthesis gene expression in the cyanobacterium Synechocystis sp. Strain PCC 6803.

We have identified genes in the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 that are involved with redox control of photosynthesis and pigment-related genes. The genes, rppA (sll0797) and rppB (sll0798), represent a two-component regulatory system that controls the synthesis of photosystem II (PSII) and PSI genes, in addition to photopigment-related genes. rppA (regulator of photosynthesis- and photopigment-related gene expression) and rppB exhibit strong sequence similarity to prokaryotic response regulators and histidine kinases, respectively. In the wild type, the steady-state mRNA levels of PSII reaction center genes increased when the plastoquinone (PQ) pool was oxidized and decreased when the PQ pool was reduced, whereas transcription of the PSI reaction center genes was affected in an opposite fashion. Such results suggested that the redox poise of the PQ pool is critical for regulation of the photosystem reaction center genes. In Delta rppA, an insertion mutation of rppA, the PSII gene transcripts were highly up-regulated relative to the wild type under all redox conditions, whereas transcription of phycobilisome-related genes and PSI genes was decreased. The higher transcription of the psbA gene in Delta rppA was manifest by higher translation of the D1 protein and a concomitant increase in O(2) evolution. The results demonstrated that RppA is a regulator of photosynthesis- and photopigment-related gene expression, is involved in the establishment of the appropriate stoichiometry between the photosystems, and can sense changes in the PQ redox poise.

Amino Acid Sequence↗