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Biomedical subjects

J Liu

Publications and source records attributed to J Liu.

At least 955 records · Page 53Linked to original sources
PubMed1999

Sustained esophageal contraction: a marker of esophageal chest pain identified by intraluminal ultrasonography.

BACKGROUND & AIMS: Intraluminal pressure recording systems have not demonstrated predictable esophageal motor correlates of unexplained chest pain. This study used continuous high-frequency intraluminal ultrasonography to characterize esophageal contraction at the time of spontaneous and provoked chest pain. METHODS: Intraluminal pressure, pH, and ultrasound images of the esophagus were recorded for a maximum of 24 hours in 10 subjects with unexplained chest pain. Changes in esophageal muscle thickness were measured as a marker of muscle contraction. Ten additional subjects with suspected esophageal chest pain were studied after edrophonium chloride injection to provoke symptoms. Ten healthy subjects were studied as controls. RESULTS: Eighteen of 24 spontaneous chest pain episodes were preceded by a sustained esophageal contraction (SEC) detected on ultrasonography (mean duration, 68.0 seconds). This motor pattern was not accompanied by changes in intraluminal pressure. Four of 24 asymptomatic control periods were accompanied by SEC, although these contractions were of shorter mean duration (29.0 seconds; P < 0.001). SEC was observed in 5 subjects with a positive chest pain response to edrophonium and in none of the 5 subjects with a negative response. SEC was not detected in normal subjects. CONCLUSIONS: There is a strong temporal correlation between a previously unrecognized esophageal motor event, SEC, and both spontaneous and provoked esophageal chest pain.

Adolescent↗
PubMed1999

Molecular cloning and sequence analysis of cDNA encoding haemorrhagic toxin acutolysin A from Agkistrodon acutus.

By means of reverse transcription polymerase chain reaction, a full-length cDNA of 1632 bp is amplified from the snake venom gland total RNA of Agkistrodon acutus. Analysis of the nucleotide sequence indicates that the amplified cDNA contains a complete open reading frame encoding 413 amino acid residues including signal peptide sequence, zymogen sequence and proteinase domain. The zymogen sequence contains PKMCGVT motif which is highly conserved in almost all venom metalloproteinases. The metalloproteinase domain contains the conserved signature zinc-binding motif HEXXHXXGXXH in the catalytic region. The predicted amino acid sequence of the metalloproteinase domain is identical to the crystallographic sequence of acutolysin A and also shares high homology with other class I snake venom haemorrhagic toxins.

Agkistrodon↗
PubMed1999

Assay of malondialdehyde and other alkanals in biological fluids by gas chromatography-mass spectrometry.

The method described in this chapter allows the accurate measurement of MDA in diverse biological samples and can be extended to measurements of other alkanals. The use of GC/MS-NCI ensures specificity and sensitivity, and the ability to prepare samples without heating limits oxidation artifact. Although the widely used TBA assay for MDA does not require sophisticated equipment, its results may be of limited value as the assay is hindered by the possibility of cross reactivity and by heat-induced oxidation artifact. This GC-MS technique offers the additional advantages of efficient processing of large numbers of samples and the elimination of recovery errors by inclusion of an internal standard.

Aldehydes↗
PubMed1999

Abduction moment arm of transposed subscapularis tendon.

OBJECTIVE: The purpose of this study was to analyze the effects of the procedure of superior transposition of the subscapularis on the biomechanics of glenohumeral abduction. DESIGN: The abduction moment arms of the subscapularis muscle for the normal attachment and transposed tendon were measured on 10 cadaver shoulders and compared to that for the normal supraspinatus tendon for which it is intended to substitute. BACKGROUND: Superior transposition of the subscapularis tendon has been recommended for surgical repair of massive tears of the rotator cuff, but the effect of this procedure on shoulder biomechanics has not been reported. METHODS: The moment arm about an instantaneous center of rotation was derived, based on the slope of tendon excursion-glenohumeral angle curve. To simulate the insertion of the transposed subscapularis tendon, pseudo-insertion sites were created. RESULTS: Superior transposition of the subscapularis tendon significantly increased its abduction moment arm. The effect was optimal when the simulated insertion site was lateral rather than medial and, to a lesser extent, anterior versus posterior. CONCLUSIONS: The results provided a biomechanical rationale for subscapularis tendon transposition in restoring the loss of abduction strength of the shoulder in a massive cuff tear.

Adult↗
PubMed1999

A novel phenotype for Lardon dwarfism in miniature Bos indicus cattle suggests that the expression of growth hormone receptor 1A in liver is required for normal growth.

Mutations within the growth hormone receptor (GHR) gene that lead to an inactivated or truncated GHR protein cause abnormal growth and small adult size in a variety of species (Laron dwarfism). We studied a line of miniature Bos indicus cattle that have phenotypic (small mature size) and endocrine (increased blood growth hormone and decreased blood insulin-like growth factor-I concentrations) similarities to Laron dwarfs. Liver mRNA from miniature and control cattle was used to amplify a cDNA within the coding region of the GHR. The miniature cattle had GHR mRNA size (determined by Northern blot) and cDNA sequence that were similar to control cattle and, therefore, were unlike most Laron dwarf genotypes in which the GHR gene is mutated. Amounts of mRNA from liver as well as muscle (superficial neck and longissimus) were analyzed by ribonuclease protection assay for IGF-I, total GHR, GHR 1A (inducible, liver-specific GHR mRNA), and GHR 1B (constitutive GHR mRNA). Four control and five miniature bulls were tested. As expected, liver IGF-I mRNA was decreased in the miniature cattle (approximately 12% of control; P < 0.01). The amount of the total GHR as well as GHR 1A mRNA were also decreased in liver (17% and 19% of control, respectively; P < 0.01). Other GHR mRNA, including GHR 1B mRNA, were similar for miniature and control cattle. In muscle, there was a tendency (P < 0.10) for decreased IGF-I mRNA and increased GHR mRNA in miniature compared with control cattle. In summary, a novel phenotype for Laron dwarfism in Bos indicus cattle was associated with underexpression of GHR 1A mRNA, but not other GHR mRNA variants in liver. In addition to decreased GHR 1A mRNA, the miniature cattle had decreased liver IGF-I mRNA. Full expression of GHR 1A in liver, therefore, may be required for full liver IGF-I expression and normal growth.

Animals↗
PubMed1999

Elevation of hydrogen peroxide after spinal cord injury detected by using the Fenton reaction.

To reveal whether reactive oxygen species (ROS) play a role after spinal cord injury, we developed a unique method for assaying hydrogen peroxide (H2O2) and determined the time course of its concentration changes following impact injury to the rat spinal cord. Microdialysis was used to sample H2O2 in the extracellular space and the dialysates were collected into a vial containing salicylate and ferrous chloride (FeCl2). H2O2 collected in the vial was converted to hydroxyl radicals (*OH) by FeCl2 catalysis. 2,3- and 2,5-dihydroxybenzoic acid produced by reaction of *OH with salicylate in the collecting vial were measured by HPLC and calibrated to H2O2 concentrations. The postinjury levels of H2O2 were significantly increased (p = 0.02) for over 11 h. FeCl2 administered through the dialysis fiber catalyzes H2O2 conversion in the cord to *OH. This *OH does not reach the collecting vial due to its extremely short lifetime (nanoseconds). The reduced H2O2 levels in the vials validate the measurement of H2O2. The relatively long-lasting formation of H2O2 and superoxide reported herein and previously suggests that ROS may be important in secondary spinal cord damage and that removal of ROS may be a realistic treatment strategy for reducing injury caused by free radicals.

Animals↗
PubMed1999

Increased prevalence of patent foramen ovale in patients with severe chronic obstructive pulmonary disease.

This study was designed to assess the prevalence of patent foramen ovale (PFO) in patients with severe chronic obstructive pulmonary disease (COPD) and the magnitude of any effects of right-to-left interatrial PFO shunting on systemic arterial oxygen desaturation after the Valsalva maneuver. The prevalence of PFO was compared between a group of 20 patients with severe chronic obstructive pulmonary disease (FEV1% <50%; FEV1/FVC <50%) and 20 control subjects (FEV1% >70%; FEV1/FVC >70%) by contrast transesophageal echocardiography during the Valsalva maneuver with simultaneous measurement of systemic arterial oxygen saturation (SaO2) by pulse oximetry. Patients with severe COPD (FEV1 = 27.2% +/- 8.4%; FEV1 /FVC = 44.3% +/- 11.0%) had a significantly higher pulmonary artery systolic pressure (38.3 +/- 7.3 vs 21.0 +/- 2.4 mm Hg; P <.005), higher prevalence of PFO (14/20 = 70% vs 7/20 = 35%; P <.05), and greater systemic arterial desaturation after Valsalva (Sao2 change: -2.6% +/- 1.4% vs -1.1% +/- 0.9%; P <.005) than control subjects. In the severe COPD group, the degree of systemic arterial desaturation after Valsalva in patients with PFO was significantly greater than in patients without PFO (Sao2 change: -3.1% +/- 1.4% vs -1.5% +/- 0. 5%; P <.05). Significant systemic arterial oxygen desaturation was observed after Valsalva in 45% of patients with interatrial PFO shunting and severe COPD. This significantly correlated with the degree of pulmonary hypertension (r = 0.6; P <.05). We conclude (1) that patients with severe COPD have an increased prevalence of PFO and (2) that approximately one half of subjects with severe COPD and PFO demonstrate statistically significant systemic arterial oxygen desaturation after the Valsalva maneuver.

Aged↗
PubMed1999

Bronchial smooth muscle hypoplasia in mouse embryonic lungs exposed to a laminin beta1 chain antisense oligonucleotide.

We used an antisense oligonucleotide (ODN) to inhibit laminin (LM) beta1 chain synthesis in mouse embryonic lung explants and cell cultures. The ODN spanned 17 bases located 13 bases downstream the initiation codon and contained phosphorothioate and C-5 propynyl pyrimidine modifications. Penetration of the ODN into the lung explants was confirmed by fluorescein isothiocyanate (FITC) tagging. 50 microM of antisense ODN decreased LM beta1 chain synthesis by 82+/-6.9% with no significant changes in the synthesis of other LM chains. The same antisense probe but without C-5 propynyl pyrimidine modification, another 17-mer ODN complementary to the LM beta1 initiation codon, and a 17-mer ODN complementary to the LM alpha1 initiation codon had no antisense activity. Lung explants exposed to the active LM beta1 antisense ODN showed decreased LM-1 and collagen type IV deposition at the epithelial-mesenchymal interface and an arrest in bronchial smooth muscle (SM) development. Histological examination and cell motility assays suggested that this arrest was due to impaired spreading and migration of SM cell precursors over the defective basement membrane (BM). Our studies indicate that beta1-chain containing LMs play a role in bronchial myogenesis.

Animals↗
PubMed1999

Formulation of a protein with propellant HFA 134a for aerosol delivery.

The purpose of this study was to investigate the formulation and delivery of a protein in a pressurized metered-dose inhaler (pMDI) containing HFA 134a as the propellant for aerosol delivery. Ethanol and surfactants, including polyoxyethylene 10 oleyl ether (Brij 97), polyoxyethylene 20 oleyl ether (Brij 98), polyoxyethylene sorbitan monooleate (Tween 80) and Aerosol OT (AOT), were investigated as formulation adjuvants to improve the dose delivery characteristics of the model protein (bovine serum albumin) containing pMDI formulations. The aqueous solution of a surfactant and protein was lyophilized to obtain a solid carrier system of the protein. Readily dispersible suspensions were obtained by suspending this solid carrier system in HFA 134a with ethanol as a dispersing aid. The formulations containing Tween 80 resulted in the highest respirable fraction. This study suggested a potential formulation containing a lyophilized complex of surfactant and protein readily dispersible in HFA 134a for delivering a therapeutic protein to the respiratory tract by inhalation.

Aerosols↗
PubMed1999

Influence of formulation technique for hydroxypropyl-beta-cyclodextrin on the stability of aspirin in HFA 134a.

The objective of this study was to determine the influence of the formulation technique for 2-hydroxypropyl-beta-cyclodextrin (HP beta CD) on the stability of aspirin in a suspension-based pressurized metered-dose inhaler (pMDI) formulation containing a hydrofluoroalkane (HFA) propellant. HP beta CD was formulated in a pMDI as a lyophilized inclusion complex or a physical mixture with aspirin. A pMDI formulation containing aspirin alone was used as the control. The chemical stability of aspirin in each pMDI formulation was determined over 6-months storage at 5, 25 and 40 degrees C. The quantity of water taken up into the pMDI canister was determined by Karl Fisher titration after storage for 6 months. Differential scanning calorimetry (DSC) was used to confirm the formation of a complex between HP beta CD and aspirin. Aspirin in the lyophilized inclusion complex exhibited the most significant degree of degradation during the 6-months storage, while aspirin alone in the pMDI demonstrated a moderate degree of degradation. Aspirin formulated in the physical mixture displayed the least degree of degradation. The water uptake study showed that water ingress occurred to the greatest extent for formulations containing aspirin and HP beta CD physical mixture, and to the least extent for formulations containing aspirin alone. Finally, the DSC study indicated that an inclusion complex was formed in situ in the pMDI formulations containing the HP beta CD and aspirin physical mixture. In conclusion, HP beta CD may be used to enhance the stability of a chemically labile drug, but the drug stability may be affected by the method of preparation of the formulation.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1999

Influence of calcium ions on the structure and stability of recombinant human deoxyribonuclease I in the aqueous and lyophilized states.

The effect of calcium ions on the structure and stability of recombinant human DNase I (rhDNase) in the aqueous and solid (lyophilized) states was investigated. Fourier transform infrared (FTIR) spectroscopy was used to examine the overall secondary structure, while chemical stability was monitored in terms of deamidation and soluble aggregate formation at 40 degrees C. The exogenous calcium was removed by EGTA. This process can remove all but approximately one calcium ion per protein molecule. Analysis of the FTIR spectra in the amide III region in either the aqueous or lyophilized state demonstrated that removal of exogenous Ca2+ by EGTA-treatment had little effect on the secondary structure (and lyophilization-induced rearrangement thereof). For the aqueous solution, circular dichroism was used as an independent technique and confirmed that there was no large overall change in the secondary or tertiary structure upon the removal of calcium. The primary degradation route for the aqueous protein was deamidation. For the EGTA-treated protein, there was also severe covalent aggregation, e.g., formation of intermolecular disulfides facilitated by the cleavage of Cys173-Cys209. The aggregates exhibited a markedly different secondary structure compared to the native protein. For instance, the beta-sheet band observed at ca. 1620 cm-1 wavenumber in the amide I second derivative spectra was increased. Enzymatic activity was completely lost upon aggregation, consistent with the cleavage of the aforementioned native disulfide. For the protein lyophilized in the presence of Ca2+, there was no increase in deamidated species during solid-state storage; however, some aggregation was observed. For the lyophilized EGTA-treated protein, aggregation was even more pronounced, and there was some loss in enzymatic activity upon reconstitution. Thus, the removal of calcium ions by EGTA-treatment decreased the stability of rhDNase in both the aqueous and solid states even though no large overall calcium-induced structural changes could be observed by the techniques used in this study.

Calcium↗
PubMed1999

Investigation of protein-surfactant interactions by analytical ultracentrifugation and electron paramagnetic resonance: the use of recombinant human tissue factor as an example.

PURPOSE: The purpose of this work is to utilize electron paramagnetic resonance (EPR) spectroscopy in conjunction with analytical ultracentrifugation (AUC) to investigate the binding of surfactants to proteins with a transmembrance domain. As an example these methods have been used to study the interaction of a nonionic surfactant, C12E8, to recombinant human tissue factor (rhTF) in liquid formulations. The complementary nature of the two techniques aids in data interpretation when there is ambiguity using a single technique. In addition to binding stoichiometries, the possibility of identifying the interacting domains by using two forms of rhTF is explored. METHODS: Two recombinant, truncated forms of human tissue factor were formulated in the absence of phospholipids. Neither of the recombinant proteins, produced in E. coli, contains the cytoplasmic domain. Recombinant human tissue factor 243 (rhTF 243) consists of 243 amino acids and includes the transmembrane sequences. Recombinant human tissue factor 220 (rhTF 220), however, contains only the first 221 amino acids of the human tissue factor, lacking those of the transmembrane region. EPR and AUC were used to investigate the interactions between these two forms of rhTF and polyoxyethylene 8 lauryl ether, C12E8. RESULTS: Binding of C12E8 to rhTF 243 is detected by both EPR spectroscopy and AUC. Although a unique binding stoichiometry was not determined, EPR spectroscopy greatly narrowed the range of possible solutions suggested by the AUC data. Neither technique revealed an interaction between rhTF 220 and C12E8. CONCLUSIONS: The complementary nature of EPR spectroscopy and AUC make the combination of the two techniques useful in data interpretation when studying the interactions between rhTF and C12E8. By utilizing these techniques in this study, the binding stoichiometry of rhTF 243 to C12E8 ranges from 1.2:1 to 1.3:0.6 based on an aggregation number of 120. This binding is consistent with previously reported activity data that showed an increase in clotting rate when rhTF 243 is in the presence of C12E8 micelles. From the rhTF 220 data, it can further be concluded that the transmembrane domain of rhTF is necessary for interactions with C12E8.

Electron Spin Resonance Spectroscopy↗
PubMed1999

Stress, aging, and brain oxidative damage.

Stress may contribute to aging acceleration and age-related degenerative diseases. Stress and adaptation to stress require numerous homeostatic adjustments including hormones, neurotransmitters, oxidants, and other mediators. The stress-induced hormones, neurotransmitters, and oxidants all have beneficial, but also harmful effects if out of balance. Therefore, the homeostasis of stress and adaptation should be governed by the hormone balance, neurotransmitter balance, and oxidant balance, as well as the interactions among these substances. The imbalance and the over-interaction of these balances may ultimately cause increased oxidant generation and oxidative damage to biomolecules. This increased oxidative damage may add to the oxidant burden associated with normal aerobic metabolism, which in itself, generates oxidants, causes accumulation of oxidative damage in mitochondria, and contributes to normal aging. Therefore, the stress-associated increase of oxidative damage may, in part, contribute to stress-associated aging acceleration and age-related neurodegenerative diseases.

Aging↗
PubMed1999

HLA-DR-DQ alleles and HLA-DP alleles are independently associated with susceptibility to different stages of post-schistosomal hepatic fibrosis in the Chinese population.

Abstract: Evaluation of human leukocyte antigen (HLA) class I and class II genes was performed on patients from China with Schistosomiasis japonica. Patients were categorized as grade 0 (n=44), grade I (n=81), grade II (n=99), or grade III (n=6) based on increasing severity of hepatic fibrosis due to repeated Schistosoma japonicum infections. These results show that the HLA-DRB1*1101-DQA1*0501-DQB1*0301 (Pc<0.02) and HLA-DRB1*1501-DRB5*0101 (Pc<0.02) haplotypes are associated with protection and susceptibility to grade I fibrosis, respectively, and that the HLA-DPA1*0103 -DPB1*0201 haplotype (Pc<0.02) is associated with protection from both grade II and III severe fibrosis. There was no association between HLA-B DNA haplotypes and the disease. These findings indicate that the HLA-class II molecules play a role in preventing or promoting fibrotic liver change after deposition with Schistosome eggs. Moreover, a tendency was observed within the HLA class II genes for the HLA-DR-DQ alleles to be associated with protection against early changes in liver fibrosis, whereas HLA-DP alleles were associated with protection from the late phase of fibrosis or severe hepatosplenic schistosomiasis.

Alleles↗
PubMed1999

Correction of chromosomal point mutations in human cells with bifunctional oligonucleotides.

A sequence-specific genomic delivery system for the correction of chromosomal mutations was designed by incorporating two different binding domains into a single-stranded oligonucleotide. A repair domain (RD) contained the native sequence of the target region. A third strand-forming domain (TFD) was designed to form a triplex by Hoogsteen interactions. The design was based upon the premise that the RD will rapidly form a heteroduplex that is anchored synergistically by the TFD. Deoxyoligonucleotides were designed to form triplexes in the human adenosine deaminase (ADA) and p53 genes adjacent to known point mutations. Transfection of ADA-deficient human lymphocytes corrected the mutant sequence in 1-2% of cells. Neither the RD or TFD individually corrected the mutation. Transfection of p53 mutant human glioblastoma cells corrected the mutation and induced apoptosis in 7.5% of cells.

Adenosine Deaminase↗
PubMed1999

Ex vivo expansion of enriched CD34+ cells from neonatal blood in the presence of thrombopoietin, a comparison with cord blood and bone marrow.

Neonatal blood (NB) contains substantial numbers of stem and progenitor cells which decline rapidly after birth. Using a combination of cord blood (CB) and NB, we performed a successful, sibling transplant for a thalassaemia patient, leading to the proposal that NB could be used as an adjunct to CB for transplantation. This study was aimed at addressing the feasibility of expanding NB and thus minimizing the volume needed from a NB collection. In the presence of early acting cytokines interleukin-1beta (IL-1beta), IL-3, IL-6, stem cell factor (SCF), flt-3 ligand with and without thrombopoietin (Tpo), we compared the expansion capacity of CD34+ enriched cells from CB, NB and bone marrow (BM). Flow cytometry and colony-forming unit (CFU) analyses show that Tpo significantly increased the expansion of CD34+ cells from CB and NB to early and committed progenitors. No significant difference was observed between the expansion of CB and NB at 7, 14 or 21 days of culture in terms of CFU, CD34+ and CD61+ cell subsets. The expansion capacity of BM was significantly lower than that of NB or CB, possibly related to the low proportion of CD34+ CD38- cells observed at day 0. There was a relatively rapid expansion of NB which was evident at day 7 whilst the expansion of CB and BM remained low, suggesting a speedy maturation process in the postnatal infant. The expanded cells, being heterogeneous in their morphology and cell surface marker expression, were mostly of the myeloid lineage (CD45+, CD33+ and HLA-DR+). Our results showed that the expansion capacity of NB is comparable to that of CB and if transplanted, the expanded products of NB might contribute to the engraftment kinetics of the neutrophil and megakaryocyte lineage.

Antigens, CD34↗
PubMed1999

Life cycle variation and the genetic structure of nematode populations.

Few data are available on population genetic structure in nematode species, and little of the available data allows direct comparison of the genetic structures of species having different life cycles. Here we use mtDNA sequence data to describe the genetic structure of a heterorhabditid nematode, and compare results to published data on other nematode species. Heterorhabditis marelatus is a parasite of soil-dwelling insects. Its life cycle and local ecology should result in small effective population sizes and restricted gene flow. As predicted, H. marelatus shows much lower mtDNA diversity within populations and over the species as a whole, and has a much more strongly subdivided population structure, than parasites of mobile vertebrate hosts. From data such as these we can begin to generalize about the effects of life cycle variation on genetic structure in different nematode species.

Animals↗