Biomedical subjects

J C Yang

Publications and source records attributed to J C Yang.

At least 73 records · Page 4Linked to original sources

PubMed1998

Conformation and ion-channeling activity of a 27-residue peptide modeled on the single-transmembrane segment of the IsK (minK) protein.

IsK (minK) protein, in concert with another channel protein KVLQT1, mediates a distinct, slowly activating, voltage-gated potassium current across certain mammalian cell membranes. Site-directed mutational studies have led to the proposal that the single transmembrane segment of IsK participates in the pore of the potassium channel [Takumi, T. (1993) News Physiol. Sci. 8, 175-178]. We present functional and structural studies of a short peptide (K27) with primary structure NH2-1KLEALYILMVLGFFGFFTLGIMLSYI27R-COOH, corresponding to the transmembrane segment of IsK (residues 42-68). When K27 was incorporated, at low concentrations, into phosphatidylethanolamine, black-lipid membranes, single-channel activity was observed, with no strong ion selectivity. IR measurements reveal the peptide has a predominantly helical conformation in the membrane. The atomic resolution structure of the helix has been established by high-resolution 1H NMR spectroscopy studies. These studies were carried out in a solvent comprising 86% v/v 1,1,1,3,3,3-hexafluoro-isopropanol-14% v/v water, in which the IR spectrum of the peptide was found to be very similar to that observed in the bilayer. The NMR studies have established that residues 1-3 are disordered, while residues 4-27 have an alpha-helical conformation, the helix being looser near the termini and more stable in the central region of the molecule. The length (2. 6 nm) of the hydrophobic segment of the helix, residues 7-23, matches the span of the hydrocarbon chains (2.3 +/- 0.25 nm) of fully hydrated bilayers of phosphatidylcholine lipid mixture from egg yolk. The side chains on the helix surface are predominantly hydrophobic, consistent with a transmembrane location of the helix. The ion-channeling activity is believed to stem from long-lived aggregates of these helices. The aggregation is mediated by the pi-pi stacking of phenylalanine aromatic rings of adjacent helices and favorable interactions of the opposing aliphatic-like side chains, such as leucine and methionine, with the lipid chains of the bilayer. This mechanism is in keeping with site-directed mutational studies which suggest that the transmembrane segment of IsK is an integral part of the pore of the potassium channel and has a similar disposition to that in the peptide model system.

Amino Acid Sequence↗

PubMed1998

Antibody to a Helicobacter pylori species specific antigen in patients with adenocarcinoma of the stomach.

This study attempted to identify a possible antibody response to Helicobacter pylori, which is associated with patients with adeno-carcinoma of the stomach. By using proteins of H. pylori as the antigen, pooled sera from gastric cancer and non-cancer patients were used as the first antibody for Western blot analysis. Antibody responses to a 26 kD secreted protein were observed in pooled cancer sera, but not in pooled sera from non-cancer patients. The protein was purified, while amino acid sequences revealed that it was a H. pylori species specific protein. The gene of this protein was cloned and a recombinant protein was expressed in E. coli. In addition, an antibody to the recombinant protein was tested in each individual patient using Western blot analysis. None of the forty non-gastric cancer patients were positive for the antibody to the recombinantly expressed 26 kD species specific protein. Meanwhile, six of the twenty four cancer patients tested positive (0/40 vs 6/24, p < 0.01). Results presented herein demonstrate that the species specific protein of H. pylori can be useful in detecting H. pylori associated with adenocarcinoma of the stomach.

Adenocarcinoma↗

PubMed1998

Induction of the mitochondrial permeability transition causes release of the apoptogenic factor cytochrome c.

It was recently reported that the mitochondrial protein cytochrome c is required for the induction of apoptosis, and that the overexpression of Bcl-2 caused increased retention of this apoptogenic factor by mitochondria. Several cellular toxins, including H2O2, tBOOH and Ca++, induce the Mitochondrial Permeability Transition (MPT); we tested the possibility that MPT is an intracellular sensor of toxicity that results in the release of cytochrome c. We observe that the release of cytochrome c from purified mitochondria is stimulated by the classical inducers of MPT, and is inhibited by the classical inhibitor of MPT, cyclosporin A (CsA). After induction of MPT, mitochondrial supernatants gained the activity to induce cleavage of caspase 3 (CPP32) in cytosolic extracts, and this gain of activity was inhibited by CsA pretreatment of mitochondria, and was cancelled by immunodepletion of cytochrome c from the supernatants. After induction of MPT, mitochondrial supernatants mixed with or without cytosolic extract gained the activity to ladder nuclei, and this gain of activity was inhibited by CsA pretreatment of mitochondria, and cancelled by immunodepletion of cytochrome c from the supernatants. These results demonstrate that the induction of MPT causes release of cytochrome c from mitochondria, which is required for the hallmarks of cytosolic and nuclear apoptosis, caspase 3 activation and nuclear laddering, and identify the MPT as a potential intracellular sensor of oxidants and other toxins, and as a target for the pharmacological inhibition of apoptosis.

Animals↗

PubMed1998

Isolation of merozoite rhoptries, identification of novel rhoptry-associated proteins from Plasmodium yoelii, P. chabaudi, P. berghei, and conserved interspecies reactivity of organelles and proteins with P. falciparum rhoptry-specific antibodies.

Rhoptries were isolated from merozoites of P. yoelii (17 XL), P. chabaudi adami and P. berghei (K-173), using sucrose gradient density centrifugation. Mouse antisera was prepared against the organelles and characterized. Antibodies specific for a known P. yoelii rhoptry protein were used to identify gradient fractions containing rhoptries and electron microscopy was used to confirm rhoptry enrichment and organelle morphology. Western blotting analysis of the gradients with organelle-specific antisera from each species, revealed several major cross-reactive interspecies protein bands of approximately 235, 210, 180, 160/170, 140, and 96-110 kDa, predominantly in densities of 1.12 and 1.15 g/ml. The parasite origin of the proteins was verified by immunoprecipitation, and reactive epitopes localized to the rhoptries by IEM. By Western blotting antisera specific for P. falciparum rhoptries reacted with protein bands of approximately 96-110 kDa in schizont extracts, and gradient fractions of density 1.12 and 1.15 g/ml from all three rodent malaria species, as well as with the rhoptries in P. yoelii, P. chabaudi, and P. berghei merozoites by IEM. We conclude that the three rodent malaria species and P. falciparum share conserved interspecies epitopes.

Animals↗

PubMed1998

Macronodular multi-organs tuberculoma: CT and MR appearances.

The case of a 21-year-old woman presenting with macronodular multi-organs tuberculoma is reported. She was examined for pulmonary tuberculosis on a chest X-ray film in January, 1995, and admitted with a cough, anorexia, and abdominal pain in July, 1996. Computed tomography revealed multiple calcified nodules with peripheral hypodense areas in the brain, and calcified hypodense masses in the liver and spleen. Magnetic resonance (MR) imaging showed hypointense masses in the liver and spleen on T1-weighted spin echo images and a hypointense mass with a hyperintense area on T2-weighted spin echo images. On contrast-enhanced dynamic MR images, the liver and spleen masses were unenhanced and hypointense with slight rim enhancement. T2-weighted spin echo images showed a round hypointense nodule in the right kidney and hydronephrosis and enlargement in the left kidney. Antituberculous treatment was started with a gradual improvement in her signs and symptoms. Her temperature became normal. However, she was systemically treated with antituberculous chemotherapy 10 months later, her condition worsened again. She died from increased intracranial pressure in August, 1997.

Adult↗

PubMed1998

Lethal injuries and time to death in a level I trauma center.

BACKGROUND: The purpose of this study was to identify the causes and time to death of all trauma victims who died at a level I trauma center during an 11-year period. STUDY DESIGN: Autopsies were performed on all patients who died secondary to trauma. Retrospective review of these autopsies was carried out and appended to existing trauma registry data. Standard definitions were used to attribute the cause of death in each case. Preventable deaths were determined by a standardized peer review process. RESULTS: Between January 1985 and December 1995, a total of 900 trauma patients died. This represented 7.3% of all major trauma admissions (12,320). Seventy percent of these patients died within the first 24 hours of admission. Thoracic vascular and central nervous system (CNS) injuries were the most common causes of death in the first hour after admission to the hospital. CNS injuries were the most common causes of death within the 72 deaths after admission. Acute inflammatory processes (multiple organ failure, acute respiratory distress syndrome, and pneumonia) and pulmonary emboli were the leading causes of death after the first 72 hours. Overall, 43.6% (393 of 900) of all trauma deaths were caused by CNS injuries, making this the most common cause of death in our study. The preventable death rate was 1%. CONCLUSIONS: The first 24 hours after trauma are the deadliest for these patients. Primary and secondary CNS injuries are the leading causes of death. Prevention, early identification, and treatment of potentially lethal injuries should remain the focus of those who treat trauma patients.

Accidents, Traffic↗

PubMed1998

A T cell-independent antitumor response in mice with bone marrow cells retrovirally transduced with an antibody/Fc-gamma chain chimeric receptor gene recognizing a human ovarian cancer antigen.

In order to treat common cancers with immunotherapy, chimeric receptors have been developed that combine the tumor specificity of antibodies with T-cell effector functions. Previously, we demonstrated that T cells transduced with a chimeric receptor gene against human ovarian cancer were able to recognize ovarian cancer cells in vitro and in vivo. We now report that recipients of bone marrow cells transduced with these genes exhibited significant antitumor activity in vivo. Moreover, in vivo depletion of T cells in reconstituted mice did not affect antitumor activity, suggesting that other immune cells expressing the chimeric receptor gene may play an important role in tumor rejection.

Animals↗

PubMed1998

Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma.

The cloning of the genes encoding cancer antigens has opened new possibilities for the treatment of patients with cancer. In this study, immunodominant peptides from the gp100 melanoma-associated antigen were identified, and a synthetic peptide, designed to increase binding to HLA-A2 molecules, was used as a cancer vaccine to treat patients with metastatic melanoma. On the basis of immunologic assays, 91% of patients could be successfully immunized with this synthetic peptide, and 13 of 31 patients (42%) receiving the peptide vaccine plus IL-2 had objective cancer responses, and four additional patients had mixed or minor responses. Synthetic peptide vaccines based on the genes encoding cancer antigens hold promise for the development of novel cancer immunotherapies.

Adult↗

PubMed1998

Increased nausea and dizziness when using tramadol for post-operative patient-controlled analgesia (PCA) compared with morphine after intraoperative loading with morphine.

Thirty-eight ASA I-III patients undergoing lower abdominal operations were randomly allocated to receive either morphine (group M, patient-controlled analgesia bolus = 1 mg of morphine) or tramadol (group T, patient-controlled analgesia bolus = 10 mg of tramadol) for post-operative patient-controlled analgesia (PCA) after receiving morphine intraoperatively. There were no between-group differences in the pain, sedation or vomit scores. The nausea scores were significantly higher in group T in the initial 20 h and between 32 and 36 h (P < 0.01, 0-4 and 8-12 h; P < 0.05, 4-8, 12-16, 16-20 and 32-36 h). The incidence of dizziness was also significantly higher in group T (68.4% vs. 31.6%, group T vs. group M, P < 0.05). There was no difference in the overall satisfaction. We conclude that the use of tramadol, compared with morphine, for post-operative PCA after intraoperative loading with morphine is associated with more nausea and dizziness, but with similar sedation, quality of analgesia and patient satisfaction.

Abdomen↗

PubMed1998

Vacuolating toxin gene polymorphism among Helicobacter pylori clinical isolates and its association with m1, m2, or chimeric vacA middle types.

BACKGROUND: Helicobacter pylori vacuolating cytotoxin encoded by vacA plays an essential role in H. pylori-related pathogenesis. Specific vacA alleles are believed to be associated with increased virulence. Association among vacA polymorphism, vacA middle genotypes, and various H. pylori-related diseases was thus investigated. METHODS: Eighty-nine isolates from patients with various gastrointestinal diseases were examined for restriction fragment length polymorphism (RFLP) of the 2.0-kb polymerase chain reaction-amplified vacA middle region. Further genetic heterogeneity was assessed with ureA-ureB RFLP. RESULTS: Twenty-eight distinct vacA RFLPs were seen among 89 isolates. Each pattern was associated with one specific vacA middle genotype. The association of specific RFLPs with certain clinical manifestations was noted among six common groups. Further RFLP analysis of the 2.4-kb ureA-ureB segment from isolates in four popular vacA RFLPs showed high genetic variation. CONCLUSIONS: The vacA genetic polymorphism may be associated with different gastrointestinal diseases.

Bacterial Proteins↗

PubMed1998

Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2: identification of the antigens mediating response.

OBJECTIVE: To determine the durability of complete responses in patients with metastatic melanoma or renal cancer treated with high-dose bolus interleukin-2 (IL-2) as well as the factors associated with the development of a complete response and the antigens mediating clinical responses. METHODS: A consecutive series of 409 patients with either metastatic melanoma or renal cancer who were treated with high-dose bolus IL-2 in the Surgery Branch, National Cancer Institute, between September 1985 and November 1996 have been analyzed with a median potential follow-up of 7.1 years. All patients were treated with 720,000 IU/kg administered by 15-minute intravenous infusions every 8 hours for up to 5 days as clinically tolerated per cycle. Two cycles constituted a treatment course. Tumor-infiltrating lymphocytes (TIL) from melanoma patients were used to clone the genes encoding the tumor antigens responsible for clinical responsiveness. RESULTS: Thirty-three of 409 (8.1%) patients treated with high-dose bolus IL-2 achieved a complete response and 37 (9%) achieved a partial response. Complete regression was seen in 6.6% and 9.3% of patients with metastatic melanoma and renal cancer, respectively. Twenty-seven of these 33 completely responding patients (82%) remain in ongoing continuous complete response from 39 to more than 148 months from the onset of treatment. Tumor regressions were seen at virtually all organ sites. The absence of prior treatment with immunotherapy, the total dose of IL-2 administered, and the maximal rebound lymphocytosis after cessation of IL-2 correlated with achieving a complete response. Expression cloning techniques have identified a series of tumor antigens that are recognized by TIL grown from resected melanomas. These antigens are mainly melanoma/ melanocyte differentiation antigens, although mutated intracellular proteins can also serve as antigens. CONCLUSIONS: Treatment with high-dose bolus IL-2 mediates complete cancer regression in approximately 8% of patients with metastatic renal cancer and melanoma. The great majority of these patients will enter durable complete regressions and appear to be cured of their metastatic cancer. Thus, immunotherapy with high-dose bolus IL-2 should be considered as initial therapy for appropriately selected patients with metastatic melanoma and renal cell cancer. Identification of the tumor antigens mediating clinical response is opening new therapeutic possibilities for cancer treatment.

Adolescent↗

PubMed1998

Ultrastructural study of extraocular muscle in congenital nystagmus.

To determine the mechanism of congenital nystagmus (CN), the ultrastructure of the extraocular muscle in CN patients was examined with the transmission electron microscope. The specimen of muscle tissue was taken during surgery from horizontal recti in the slow and quick phase sides separately in the jerky type, and medial and lateral recti in the pendular type. The extraocular muscle was immediately fixed in 2.5% glutaraldehyde solution. (1) In the jerky type, the myocytes in the quick phase side showed myofibrillae that were perpendicular to axes of myocytes and had the structure of sarcomeres. In the slow phase side there were perpendicular myofibrillae in the periphery of myocytes. (2) In the pendular type, there were no perpendicular myofibrillae within myocytes. The myofibrillae that were parallel to the axes of myocytes were arranged disorderly. The length of the H and I bands in different myofibrillae was not identical. These results demonstrated, for the first time, the ultrastructural changes in the extraocular muscle of CN patients, which might provide the pathological basis for this disease.

Adolescent↗

PubMed1998

Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity.

PURPOSE: This randomized, prospective study assesses the impact of postoperative external-beam radiation therapy on local recurrence (LR), overall survival (OS), and quality of life after limb-sparing resection of extremity sarcomas. PATIENTS AND METHODS: Patients with extremity tumors and a limb-sparing surgical option were randomized to receive or not receive postoperative adjuvant external-beam radiotherapy. Patients with high-grade sarcomas received postoperative adjuvant chemotherapy whereas patients with low-grade sarcomas or locally aggressive nonmalignant tumors were randomized after surgery alone. RESULTS: Ninety-one patients with high-grade lesions were randomized; 47 to receive radiotherapy (XRT) and 44 to not receive XRT. With a median follow-up of 9.6 years, a highly significant decrease (P2 = .0028) in the probability of LR was seen with radiation, but no difference in OS was shown. Of 50 patients with low-grade lesions (24 randomized to resection alone and 26 to resection and postoperative XRT), there was also a lower probability of LR (P2 = .016) in patients receiving XRT, again, without a difference in OS. A concurrent quality-of-life study showed that extremity radiotherapy resulted in significantly worse limb strength, edema, and range of motion, but these deficits were often transient and had few measurable effects on activities of daily life or global quality of life. CONCLUSION: This study indicates that although postoperative external-beam radiotherapy is highly effective in preventing LRs, selected patients with extremity soft tissue sarcoma who have a low risk of LR may not require adjuvant XRT after limb-sparing surgery (LSS).

Extremities↗

PubMed1998

[The use of Cantonese pain descriptors among healthy young adults in Hong Kong].

BACKGROUND: The interpretation and expression of pain are closely related to an individual's social and cultural background. To convey messages on pain, language and words (pain descriptors) is particularly significant in assessment and evaluation of pain severity and its management. Therefore, the study of pain descriptors is crucial in clinical practice. METHODS: It was of exploratory-descriptive design. Samples were recruited by convenience. Data were collected by structured self-administered questionnaire. Data obtained included demographic information and pain descriptors used by the subjects in various pain conditions. Data were analyzed by descriptive statistics. Pain descriptors were categorized according to nature, process, intensity, aggravating factors, accompanying symptoms and behavioral manifestation. RESULTS: Total number of pain descriptors (in Cantonese) based on real pain experience was 3017, mean was 3 (n = 986). The commonest used descriptors was the nature of pain (41%). The intensity of pain constituted 20%. There was no significant difference in the number of pain descriptors between male and female. However, there was a significant difference between the type of pain descriptors used (Mfemale = 526, Mmale = 453, Z = -2.9729, p = 0.0029). There were also significant differences in the use of pain descriptors among the various age groups (X2 = 15.0157, df = 4, P = 0.0047) and educational levels (X2 = 11.2443, df = 4, P = 0.0240). The types of descriptors used increased with an increase in age and education levels. CONCLUSIONS: This exploratory-descriptive study explores the use of pain descriptors among Chinese young adults in Hong Kong. The result shows that female use more pain descriptors than male. The pain descriptors that female used are mostly of nature type. The similarities and differences in findings with those of the Ho's (1991) are compared.

Adolescent↗

PubMed1998

Optimized conditions for growth and fermentation of Helicobacter pylori.

This study attempted to optimize the growth conditions of Helicobacter pylori by comparing the growth of H. pylori in an anaerobic jar and an incubator. It was found that the primary isolation rate of H. pylori from gastric biopsies was higher in an anaerobic incubator (28/30) than in an anaerobic jar (21/30). In addition, growth rate in the subsequent passage was also higher in an incubator. By comparing different supplements in the liquid media, it was found that most strains grew best in Brucella broth containing 5% fetal calf serum, and some strains grew well with the supplement of 0.2% of beta-cyclodextrin. A large scale culture using a bioreactor indicated that a defoaming agent, polypropylenglycol, profoundly inhibited the growth of H. pylori. However, fermentation could be successfully performed by continuously infusing mixed airs composed of 5% O2, 10% CO2 and 85% N2. Moreover, the production of secreted proteins of H. pylori strains grown in the bioreactor was the same as that in an anaerobic jar. Results presented herein can be used to further optimize conditions for enhancing the growth of H. pylori.

Fermentation↗

PubMed1998

Serum interleukin-6 levels in metastatic renal cell carcinoma before treatment with interleukin-2 correlates with paraneoplastic syndromes but not patient survival.

PURPOSE: We sought to determine the frequency of interleukin-6 (IL-6) expression in renal cancer cell lines, the frequency of the detection of IL-6 in the serum of patients with metastatic renal cell carcinoma, whether serum IL-6 level correlates with the development of paraneoplastic syndromes and whether serum IL-6 level in patients with metastatic renal cancer correlates with response to treatment with interleukin-2 (IL-2) or patient survival. MATERIALS AND METHODS: Conditioned media from 21 cell lines from 20 patients were examined for IL-6. We identified 2 matched groups of patients with metastatic renal cancer (30 responders and 29 nonresponders) to IL-2 based immunotherapy. Stored pretreatment serum specimens were evaluated for IL-6. Medical records were reviewed to determine the presence of paraneoplastic syndromes. RESULTS: IL-6 was detected in 19 of 21 renal cancer cell lines (90%) obtained from 20 patients with metastatic renal cancer as well as in the serum of 33 of 59 patients (56%) with metastatic renal cell carcinoma. A significant association between serum IL-6 level and anemia (p = 0.0032), elevated platelet count (p = 0.01), decreased albumin (p = 0.034) and elevated alkaline phosphatase (p = 0.04) was found. A trend was noted of the association of increased serum IL-6 level and fever (p = 0.051). No correlation was found between pretreatment serum IL-6 level and survival or response to IL-2. CONCLUSIONS: IL-6 was frequently secreted by renal cancer cell lines but it was only present in the serum of approximately half of the patients with metastatic renal cancer. Elevations of serum IL-6 were associated with paraneoplastic manifestations frequently seen in patients with renal cancer, including anemia, thrombocytosis, decreased albumin and elevations of alkaline phosphatase (Stauffer's syndrome). A weak relationship was noted between serum IL-6 level and fever but none was noted between that and survival or response to IL-2.

Adult↗

PubMed1998

Molecular mechanisms of clarithromycin resistance in Helicobacter pylori.

Combination antibiotic therapy for Helicobacter pylori has now become the standard means of treating peptic ulcer diseases. Clarithromycin is a newly adopted antibiotic for H. pylori eradication. However, resistance to clarithromycin reduces the efficacy of clarithromycin-containing regimens. We explored mechanisms of clarithromycin resistance by evaluating H. pylori for macrolide resistance mechanisms reported in H. pylori and other bacteria. Degenerate polymerase chain reaction analysis of the H. pylori genome failed to yield products homologous to methylase, a drug inactivation enzyme, or efflux pumps. Clarithromycin selection in Escherichia coliNM522, transformed with an expression library that was constructed with genomic DNA from a clarithromycin-resistant strain of H. pylori, revealed six clones that conferred clarithromycin resistance consistently after retransformation. Southern hybridization and DNA sequencing revealed that four of the six clones contained the same locus. Comparison of DNA and amino acid sequences showed that the 1.3-kb DNA fragment had significant homology to the 3-oxoadipate CoA-transferase subunit A (yxjD) and subunit B (yxjE) of Bacillus subtilis. However, the clarithromycin inactivation assay and knockout mutation analysis showed that the gene increased clarithromycin resistance in E. coli, but not in H. pylori. In contrast, sequencing of the 23S rRNA gene in six clarithromycin-resistant H. pylori clinical isolates revealed an A to G transitional mutation at position 2515 of the 23S rRNA gene in all isolates. Natural transformation with the 23S rRNA gene from resistant strains conferred clarithromycin resistance in clarithromycin-sensitive strains. We conclude that the 23S rRNA mutation is sufficient to confer clarithromycin resistance and that it is the major mechanism of clarithromycin resistance in H. pylori.

Amino Acid Sequence↗

PubMed1997

Role of the distal hinge region of C1-inhibitor in the regulation of C1s activity.

A synthetic peptide corresponding to residues 448-459 of C1-inhibitor (C1-inh) binds to C1s, is a non-competitive inhibitor of C1s activity and prevents formation of an SDS-stable C1s-C1-inh complex. Substitutions of residues Q452, Q453 or F455 in this peptide resulted in loss of C1s binding and inhibitory activity of the peptide. NMR analysis of the peptide showed an area of well-defined structure from E450 to F455. The side chains of Q452, Q453 and Q455 were exposed to the solvent and therefore available for C1s binding. The defined structure in the peptide is compatible with our computer model of the serpin domain of C1-inh.

Complement C1 Inactivator Proteins↗