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Biomedical subjects

J J Yang

Publications and source records attributed to J J Yang.

At least 19 recordsLinked to original sources
PubMed1996

Hepatoprotective effects of emodin from Ventilago leiocarpa.

A major component of ethyl acetate (EtOAc) and chloroform (CHCl3) fractions of Ventilago leiocarpa Bunge (Rhamnaceae), emodin, was isolated and exhibited hepatoprotective effects on carbon tetrachloride (CCl4) as well as D-galactosamine (D-GalN)-induced liver damage. The histopathological examination also clearly showed that emodin reduced lymphocyte cells, Kupffer cells, ballooning degeneration, cell necrosis and hyaline degeneration on CCl4 and D-galactosamine-induced tests.

Acetates↗
PubMed1996

Angiogenesis factor in endometrial carcinoma: a new prognostic indicator?

OBJECTIVE: Tumor angiogenesis is believed to be a prognostic indicator associated with tumor growth and metastasis. Studies of angiogenesis in breast, prostate, and lung cancer, as well as melanoma, have shown that neovascularization correlates with the likelihood of metastasis and recurrences. The purpose of this study was to evaluate microvessel density as a prognostic factor in endometrial cancer. METHODS: Between 1980 and 1991 the tumor registry identified 25 patients with a diagnosis of recurrent endometrial cancer. These patients were matched with 25 patients with nonrecurrent disease for age, stage, grade, and treatment. The histologic slides of the 50 patients were reviewed. The paraffin blocks were obtained, and the area of the deepest myometrial invasion was selected for staining. The microvessels within the invasive cancer were highlighted by means of immunocytochemical staining to detect factor VIII-related antigen. Microvessels were counted by two investigators who were blinded to the patients' clinical status. Survival data were analyzed with Kaplan-Meier survival curves. RESULTS: Microvessel count was related to likelihood of recurrence, although this trend did not reach statistical significance. Patients with tumors of low capillary density had a mean survival time of 123 months. Patients with tumors of high capillary density had a mean survival time of 75 months (p = 0.02). Among patients with recurrent disease, those with a low capillary count survived a mean of 64 months. Patients with recurrent disease with tumors of high capillary density survived a mean of 45 months (p = 0.002). CONCLUSION: Angiogenesis factor correlates with survival in endometrial carcinoma.

Aged↗
PubMed1996

Frequency of anti-bactericidal/permeability-increasing protein (BPI) and anti-azurocidin in patients with renal disease.

The major subtypes of anti-neutrophil cytoplasmic antibodies (ANCA) detected by indirect immunofluorescence assay (IFA) are P-ANCA and C-ANCA. In patients with vasculitis, myeloperoxidase (MPO) is the major P-ANCA antigen and proteinase 3 (PR3) is the major C-ANCA antigen. BPI and azurocidin, which are also called 57-kD cationic antimicrobial protein (CAP 57) and 37-kD cationic antimicrobial protein (CAP 37), respectively, have been proposed as less frequent target antigens for C-ANCA and P-ANCA. In patients with renal disease, we determined the frequency of antibodies against BPI and azurocidin. By IFA on alcohol-fixed neutrophils, monoclonal and polyclonal anti-BPI antibodies produced a C-ANCA pattern, whereas rabbit anti-azurocidin antibody produced a P-ANCA pattern. By ELISA, sera from 229 P-ANCA-positive patients, 99 C-ANCA-positive patients and 48 ANCA-negative (by IFA) patients with renal biopsies were tested for reactivity with recombinant human BPI and purified human azurocidin. Of these sera, 17.5% of P-ANCA, 30.3% of C-ANCA and 20.8% of IFA-ANCA-negative sera were positive for anti-BPI; and 8.3% of P-ANCA, 3.0% of C-ANCA and 8.3% of IFA-ANCA-negative sera were positive for anti-azurocidin. There was no statistical difference in frequency of anti-BPI between pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) and other glomerular disease (OGD), and there was a lower frequency of anti-azurocidin in NCGN samples than in OGD samples. By Western blot, anti-BPI-positive sera reacted with a 57-kD BPI band and anti-azurocidin-positive sera with a 29-kD azurocidin band. In conclusion, there is a low frequency of anti-BPI and anti-azurocidin antibodies in ANCA-positive patient sera; however, this does not correlate with NCGN, which is a marker for ANCA-associated small vessel vasculitis, and a similar positivity is found in IFA-ANCA-negative patients with renal disease. Therefore, serologic detection of anti-BPI and anti-azurocidin is not diagnostically specific in patients with renal disease.

Amino Acid Sequence↗
PubMed1996

Light catalytically cracked naphtha: subchronic toxicity of vapors in rats and mice and developmental toxicity screen in rats.

Both a subchronic inhalation study and a developmental toxicity screen were performed with vapors of light catalytically cracked naphtha (LCCN). In the subchronic study, four groups of mice and rats (10 animals per sex per species) were exposed for approximately 13 wk (6 h/d, 5 d/wk) to concentrations of LCCN vapors of 0, 530, 2060, or 7690 mg/m3. An untreated control group was also included. Animals were observed daily and body weights were taken weekly. No significant treatment-related changes were found in clinical signs, body weight, serum chemistry, hematology, histopathology of 24 tissues, or weights of 12 organs. A marginal decrease was noted in the number of sperm per gram of epididymis. In the developmental toxicity screen, presumed-pregnant Sprague-Dawley rats were exposed to 0, 2150, or 7660 mg/m3 of LCCN vapors, 6 h/d on d 0-19 of gestation. Females were sacrificed on d 20; dams and fetuses were examined grossly and fetuses were later evaluated for skeletal and visceral effects. The number of resorptions was increased by approximately 140% in the group receiving 7660 mg/m3; no other definite treatment-related changes were observed. Overall, the effects of exposure to partially vaporized LCCN were minimal.

Administration, Inhalation↗
PubMed1996

Anti-inflammatory and radical scavenge effects of Arctium lappa.

The effects of Arctium lappa L. (root) on anti-inflammatory and free radical scavenger activity were investigated. Subcutaneous administration of A. lappa crude extract significantly decreased carrageenan-induced rat paw edema. When simultaneously treated with CCl4, it produced pronounced activities against CCl4-induced acute liver damage. The free radical scavenging activity of its crude extract was also examined by means of an electron spin resonance (ESR) spectrometer. The IC50 of A. lappa extract on superoxide and hydroxyl radical scavenger activity was 2.06 mg/ml and 11.8 mg/ml, respectively. These findings suggest that Arctium lappa possess free radical scavenging activity. The inhibitory effects on carrageenan-induced paw edema and CCl4-induced hepatotoxicity could be due to the scavenging effect of A. lappa.

Animals↗
PubMed1996

Shared idiotypy among patients with myeloperoxidase-anti-neutrophil cytoplasmic autoantibody associated glomerulonephritis and vasculitis.

Anti-neutrophil cytoplasmic autoantibodies (ANCA) have been hypothesized to participate in the pathogenesis of necrotizing vasculitis based on their association with small vessel vasculitides and the in vitro ability of such antibodies to activate cytokine-primed neutrophils. Much remains to be elucidated about the factors responsible for the generation and perpetuation of these autoantibodies and the shaping of the ANCA immune response. This study evaluated the clonal diversity of the ANCA immune response in patients with myeloperoxidase-ANCA associated disease. Isoelectric focusing was used to investigate the clonality of myeloperoxidase-ANCA from 34 patients with pauci-immune necrotizing glomerulonephritis. Sixty-nine percent of the patients had two or less clonotypes to myeloperoxidase, whereas 31% had more than two clonotypes. Clonality was stable over the course of the disease and shared among some unrelated patients. Shared idiotypy was specifically investigated using a murine monoclonal anti-idiotype (7F2C11) to the anti-myeloperoxidase antibodies of one patient with ANCA associated vasculitis. This monoclonal antibody was selected by demonstrating: (1) binding to the proband's affinity purified anti-myeloperoxidase antibodies; (2) an inhibitory effect on the binding of the proband's anti-myeloperoxidase to myeloperoxidase; and (3) lack of binding to control human antibody preparations, or to the proband's crude immunoglobulin preparation, thus excluding an anti-allotype antibody. Purified 7F2C11 was immobilized on Sepharose, and this monoclonal anti-idiotype affinity column was used to search for a shared anti-myeloperoxidase idiotype in the plasma of four other patients with myeloperoxidase-ANCA associated disease. Using this column, we were able to extract anti-myeloperoxidase antibodies from plasma of the other patients but not from control antibody preparations. We concluded that most myeloperoxidase-ANCA patients have a restricted response to myeloperoxidase and that some patients share a common idiotype. The demonstration of shared idiotypy suggests a restricted number of autoreactive epitopes of the myeloperoxidase molecule, or that some anti-myeloperoxidase autoantibodies are encoded by germ line genes, or both.

Animals↗
PubMed1995

Action of dexmedetomidine on rat locus coeruleus neurones: intracellular recording in vitro.

The action of dexmedetomidine on rat locus coeruleus neurones was examined using intracellular recordings from the in vitro brain slice preparation. Concentrations of dexmedetomidine from 1 to 1000 nM were tested. At 30 nM, dexmedetomidine produced complete inhibition of firing of all neurones tested (n = 21); this was associated with a 13 mV hyperpolarization (range 2.2-29.7 mV, n = 21) and a 27% reduction in input resistance (range 11.1-46.2%, n = 17). The dexmedetomidine responses reached a plateau phase between 100 and 1000 nM. Based on single-cell recordings, the hyperpolarizing potency of dexmedetomidine was found to be 6 times greater than that of clonidine (n = 10). The reversal potential for the dexmedetomidine-induced hyperpolarization was -106.9 +/- 1.7 mV (n = 9), a value similar to the K+ equilibrium potential; hyperpolarization was blocked by both CsCl and BaCl2. The effect of dexmedetomidine was antagonized by yohimbine, with a dissociation equilibrium constant of 30 nM. In contrast, prazosin, the alpha 1-, alpha 2B- and alpha 2C-adrenoceptor subtype-preferring ligand, did not inhibit the dexmedetomidine effect. Our results also show that low concentrations of oxymetazoline (10-300 nM), an alpha 2A-adrenoceptor subtype-selective drug, cause profound inhibition of neuronal activity in the locus coeruleus. These data therefore suggest that dexmedetomidine binds to alpha 2A-adrenoceptors on the cell membrane of neurones of the locus coeruleus and that this leads to opening of the inwardly rectifying K+ channels, resulting in the observed hyperpolarization of the membrane.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1995

Conformational properties of four peptides spanning the sequence of hen lysozyme.

Four peptides encompassing the entire amino acid sequence of hen lysozyme were examined in aqueous solution and in 50% (v/v) 2,2,2-trifluoroethanol (TFE) by far-UV CD. Two peptides, 1-40 and 84-129, correspond to regions which are helical in the native protein, and together represent the alpha-domain. The beta-domain of the native enzyme was also synthesized as two peptides, one (41-60) containing the residues in the triple stranded antiparallel beta-sheet and the other (61-82) corresponding to a region lacking regular secondary structure. In water at pH 2.0 and 25 degrees C, the monomeric peptides 1-40, 41-60 and 61-82 appear to be predominantly unstructured. By contrast, the peptide 84-129 has considerable, presumably helical structure, corresponding to approximately 19%, or nine residues, on average, which can be unfolded by the addition of 8 M urea or 6 M guanidine hydrochloride. In 50% TFE the conformational properties of the four peptides are again distinct. Although little helical structure is induced in the peptides 41-60 and 61-82, and a native-like extent of helical structure is induced in the peptide 1-40, the peptide 84-29 converts almost entirely to helical structure in 50% TFE. The far-UV CD spectrum of a stoichiometric mixture of the four peptides in water resembles closely that of a denatured state of the intact protein formed by reductive methylation of its four disulphide bonds, but differs significantly from that of the native protein. The far-UV CD spectrum of the peptide mixture in TFE is indistinguishable from that of the intact protein in this solvent, both in the presence and in the absence of its four disulphide bonds. The conformational preferences of the peptides are not predicted using standard assessments of helical propensity or hydrophobicity, but correlate instead with the number of local contacts made in the native protein. On the basis of these results, we suggest that the region 84-129 could play an important role in determining the nature of the early folding events in the folding pathway of the intact polypeptide chain.

Animals↗
PubMed1995

Transformation-restoring factor: a low molecular weight secreted factor required for anchorage-independent growth of oncogene-resistant mutant cell lines.

We have previously described two independent mutant rat fibroblast cell lines that fail to form colonies in soft agar when infected with a v-H-ras-expressing retrovirus, yet still undergo transformation-related morphological alterations in response to this oncogene. We report here that conditioned medium (CM) from non-transformed rat fibroblasts contains an activity that specifically corrects this defect in the mutant cell lines, rendering them capable of anchorage-independent growth in response to ras. The major activity in CM, designated transformation-restoring factor (TRF), is approximately 1300 molecular weight, lipid insoluble, and heat, protease, acid and base stable. Latent activity, distinct from TRF, is also present in CM; several lines of evidence indicate that transforming growth factor (TGF) beta is responsible for this activity. TRF, however, cannot substitute for TGF beta in the phenotypic transformation of NRK cells. TRF activity is decreased in CM of control cells transformed by ras and this response to ras is retained by the mutant cell lines. We propose that whereas wild-type cells transformed by ras may constitutively activate a TRF-regulated pathway, thus becoming independent of TRF for growth in soft agar, these mutants have acquired dependence on an exogenous supply of TRF for this aspect of the transformed phenotype. Cellular activities regulated, directly or indirectly, by TRF may be effectors of the anchorage-independent growth property that is a hallmark of transformed rodent fibroblasts.

Animals↗
PubMed1995

Physicochemical characterization of the cytoplasmic domain of the epidermal growth factor receptor and evidence for conformational changes associated with its activation by ammonium sulphate.

The physiochemical properties of the purified cytoplasmic domain of the epidermal growth factor (EGF) receptor, its self-phosphorylation and peptide phosphorylation activities, and its activation by ammonium sulphate have been studied. Highly efficient purification procedures for the isolation of the recombinant cytoplasmic domain (Met644-Ala1186) of the EGF receptor, expressed in the baculovirus/insect cell system, are described. Physicochemical characterization of the protein included investigation of its isoelectric and hydrodynamic properties, stability, oligomeric status, and secondary structure using far-u.v. circular dichroism. The recombinant protein was not recognized by anti-phosphotyrosine antibodies, unless first self-phosphorylated in vitro. Tryptic phosphopeptide maps of self-phosphorylated recombinant cytoplasmic domain and the EGF-stimulated A431-membrane receptor were very similar, suggesting that the recombinant had similar self-phosphorylation capacity and specificity. The preparations were characterized by high specific activity towards peptide tyrosine phosphorylation. Although the cytoplasmic domain was isolated as a homogeneously monomeric protein, storage at 4 degrees C led to slow, spontaneous aggregation with reduction in specific activity. Both high activity and monomeric state were maintained by storage below 0 degree C. The dependence of the initial rate of self-phosphorylation on protein concentration was consistent with cross-phosphorylation but not with the known oligomerization-induced activation of holoreceptor. The peptide phosphorylation activity was stimulated by Mn2+, Mg2+ and (NH4)2SO4 at high concentrations. The substrate specificity of (NH4)2SO4 activation was studied using synthetic peptides. Self-phosphorylation was inhibited by (NH4)2SO4 in the range 0-0.25 M but activated at 1.0-1.5 M, possibly as a result of ionic and hydrophobic protein interactions respectively. Phosphopeptide maps of cytoplasmic domain phosphorylated in the presence of high (NH4)2SO4 showed that the protein was more extensively phosphorylated than in the absence of salt, or than the native receptor. Far-u.v. circular-dichroism spectra of the cytoplasmic domain changed dramatically at 1 M (NH4)2SO4, raising the possibility that (NH4)2SO4 activates the kinase catalytic domain by inducing conformational changes.

Ammonium Sulfate↗
PubMed1995

Computer-based information collection and feedback for Norwegian municipal health and social services.

Norway is governed by a three-tier parliamentary system where each tier is governed by a popularly selected body: the national parliament, the county councils, and the municipality councils. This three-tier system is in many ways also reflected in the organization, management, and financing of health and social services. A large amount of information (e.g.,statistics and annual reports) flows between the three levels of management. In order to have a proper and efficient information flow, The Norwegian Ministry of Health and Social Affairs has, since 1992, been conducting a nation-wide project for information collection from and feedback to municipal health and social services (see Figure 1). In this presentation, we will present the basic idea behind The Wheel. We will also discuss some of the major activities in and experiences from the project of using Information Technology to implement an electronic Wheel. The following are basic issues to consider in implementing such a system, related to the following basic issues in implementing such a system [1]: Obtaining a unified information basis to: increase the data quality, and compile "definition catalogs" that contain commonly agreed-upon definitions of central concepts and data sets that are used in the municipal health and social services [2]. Achieving electronic data collection, both in terms of the automatic selection and aggregation of relevant data from operational systems in the municipalities and in terms of using Electronic Forms. Experiments with various ways of electronically feeding back the statistics and other comparative data to the municipalities. Providing the municipal users with appropriate tools for using the statistics that are fed back.

Data Collection↗
PubMed1995

Inhibition of locus coeruleus neurons by serotonin at high doses.

Using brain slice and intracellular recording techniques, this study was conducted in the attempt to evaluate whether serotonin (5-HT) is able to directly influence neuronal activities of the locus coeruleus (LC). LC neurons in the brain slice preparation show spontaneous firing in the absence of synaptic input; neurons in this work had firing rates ranging from 0.18-3.6 Hz (mean = 1.18 +/- 0.26 Hz). Concentrations of 5-HT from 30 to 300 microM were used, which reversibly decreased the spontaneous firing rate in 30 out of 36 LC neurons tested. In testing those cells with more than one concentration, the effect was dose-dependent. For LC neurons which showed complete block of firing by 5-HT (300 microM), the latency to block was found to be directly related to the firing rate. In addition to the inhibition of spontaneous firing, 5-HT (300 microM) also caused a 0-5 mV (mean = 3.2 mV, n = 10) hyperpolarization associated with a 2.2-21% (mean = 11.5%, n = 10) decrease in input resistance. Lower concentrations of 5-HT (30-100 microM) did not produce any significant change in membrane potential or input resistance in neurons of the LC. The 5-HT receptor antagonist methysergide (10 microM) was tested in 6 cells. Methysergide antagonized the 5-HT-induced inhibition of firing, hyperpolarization and reduction in input resistance. We concluded that 5-HT has inhibitory actions at high doses when applied to LC neurons in the brain slice preparation. 5-HT's inhibitory effects on LC neurons appear to be mediated by 5-HT receptors since they are antagonized by methysergide.

Animals↗
PubMed1994

Far-UV circular dichroism reveals a conformational switch in a peptide fragment from the beta-sheet of hen lysozyme.

The conformation of a 20-residue synthetic peptide corresponding to the antiparallel triple-stranded beta-sheet in hen egg white lysozyme (residues 41-60) has been studied by circular dichroism (CD) and size-exclusion chromatography. In aqueous solution the conformation of the peptide is strongly pH dependent. At pH values below 4.0 and 25 degrees C, the far-UV CD spectrum of the peptide resembles that expected for a predominantly beta-sheet structured (low-pH form), while at pH values exceeding 4.0 the spectrum changes to that of a predominantly unstructured conformation (high-pH form). The far-UV CD spectrum of the high-pH form (pH 6.8) is not affected by changes in the concentration of the peptide and by changes in temperature and ionic strength. By contrast, the far-UV CD spectrum of the low-pH form (pH 2.0) is concentration and temperature dependent but is not affected by ionic strength. Size-exclusion chromatography trimers and higher oligomers and that the monomeric form of the peptide at low pH is predominantly random in nature. Significant helical structure was induced in the high-pH form of the peptide by both trifluoroethanol (TFE) and methanol; by contrast, the conformation of the low-pH form of the peptide was not changed with concentrations of methanol up to 50% (v/v), although in the presence of TFE a state displaying significant helical character was induced. During the transition an intermediate which also displays significant beta-sheet character but which has a distinct CD spectrum is populated. The relevance of this study to the folding pathway of the intact protein is discussed.

Amino Acid Sequence↗
PubMed1994

Kinetics of hydrolysis of dansyl peptide substrates by thermolysin: analysis of fluorescence changes and determination of steady-state kinetic parameters.

The stopped-flow fluorescence technique has been used to study the hydrolysis of 10 dansyl peptides by thermolysin. The origin of the fluorescence changes observed during the reactions has been investigated in detail. Depending on the substrate and the excitation wavelength, the dansyl fluorescence changes observed arise either from energy transfer (maximal at lambda ex = 230 and 280 nm) between Trp residues of thermolysin and the dansyl group of the substrate in enzyme-substrate (ES) complexes or from both sources. These excitation (maximal at lambda ex = 245 and 340 nm) of the free substrate and product, or from both sources. These two types of fluorescence signals reflect the concentrations of ESi and free substrate, respectively. Both types of fluorescence changes have been used to monitor the reaction progress, and different mathematical formalisms have been used to determine the kinetic parameters for the reactions with results that are in good agreement. The efficiency of Trp quenching by a series of five dansyl tripeptides is shown to be related to the fractional saturation of enzyme and follows the KM-1 values for the substrates. The quenching efficiency for a dansyl tetrapeptide is weaker due to the greater distance between the dansyl group and the Trp-115 donor in thermolysin. On the basis of these studies, substrates capable of supporting more detailed kinetic studies of thermolysin have been identified.

Amino Acid Sequence↗
PubMed1994

Differential effect of halide anions on the hydrolysis of different dansyl substrates by thermolysin.

The effect of sodium halide salts on the hydrolysis of three of the dansyl (Dns) peptide substrates described in the previous paper (Yang & Van Wart, 1994) by thermolysin have been studied. Increasing concentrations of sodium chloride decrease the KM value for the hydrolysis of the tripeptides Dns-Gly-Phe-Ala and Dns-Ala-Phe-Ala but leave kcat unaltered. This kinetic behavior is described by a nonessential activation mechanism in which chloride binds preferentially to the enzyme-substrate complex. Similar trends are found for the sodium bromide and fluoride salts. In contrast, sodium chloride decreases both KM and kcat almost equally for the hydrolysis of Dns-Ala-Ala-Phe-Ala, leaving kcat/KM unchanged. Thus, chloride is an uncompetitive inhibitor of this substrate. Molecular modeling studies have been carried out in order to explain the effect of chloride on the binding of these dansyl peptides. The decrease in KM for the hydrolysis of all three substrates is attributed to an interaction of chloride with Arg-203 located in the active site to stabilize the enzyme-substrate complexes. The differential effect of chloride on the kcat values for the hydrolysis of the dansyl tripeptides vs dansyl tetrapeptide is related to differences in binding on the Pn side of the substrates. The tripeptides are predicted to bind to the active site of thermolysin in a single low-energy conformation. However, there are two populations of low-energy binding modes for the tetrapeptide, one of which is believed to be a more productive binding mode.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗