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Biomedical subjects

Y Chang

Publications and source records attributed to Y Chang.

At least 145 records · Page 8Linked to original sources

[Recovery of gastrointestinal motility following laparoscopic versus open cholecystectomy].

OBJECTIVE: To investigate the recovery of gastrointestinal motility after laparoscopic cholecystectomy (LC) and open cholecystectomy (OC). METHODS: Motilin (MOT), gastrin (GAS), electrogastrogram (EGG), the peristaltic sound recovery timing (PSRT) and the anorectum exhaust timing (AET) were determined in 30 patients having LC and 18 patients having OC. RESULTS: MOT, GAS, EGG frequency and EGG amplitude on the first, second and third day after operation in LC group were not significantly different in comparison with preoperative data (P > 0.05), but significant difference on the first and second postoperative day compared with preoperative data and data of the the LC group (P < 0.05). The PSRT and AET in the LC group were much shorter in comparison with the OC group (P < 0.05). CONCLUSIONS: The recovery of gastrointestinal motility after LC is earlier than OC, which justifies early feeding for patients after LC.

Cholecystectomy↗

[Fractal dimension analysis of the surface EMG].

Fractal analysis is a new method for biomedical signal processing. Present research on surface EMG and its parameterization method were introduced in this paper. Experiments were performed on three conditions: (1) different muscle contraction degree, (2) different static load, (3) different motion pattern. Problems and prospects in engineering application were also discussed here.

Adult↗

TGF-beta1 somatic gene therapy prevents autoimmune disease in nonobese diabetic mice.

Nonobese diabetic (NOD) mice develop insulitis and diabetes through an autoimmune process. Since TGF-beta1 down-regulates many immune responses, we hypothesized that TGF-beta1 could prevent disease in NOD mice and that there would be several advantages to cytokine delivery by a somatic gene therapy approach. We opted for i.m. injection of a naked plasmid DNA expression vector encoding murine TGF-beta1 (pCMV-TGF-beta1). Treatment with pCMV-TGF-beta1 resulted in the retention and expression of the vector in muscle cells, associated with a considerable elevation in the plasma levels of TGF-beta1, that was not observed in control vector-treated mice. The levels of TGF-beta1 produced were sufficient to exert immunosuppressive effects. Delayed-type hypersensitivity responses were suppressed, and autoimmunity-prone NOD mice were protected from insulitis and diabetes in models of cyclophosphamide-accelerated and natural course disease. In pCMV-TGF-beta1-treated mice, pancreatic IL-12 and IFN-gamma mRNA expression was depressed, and the ratio of IFN-gamma to IL-4 mRNA was decreased, as determined by semiquantitative reverse-transcription PCR. In contrast, NOD mice injected with a vector encoding the proinflammatory cytokine IFN-gamma developed diabetes earlier. Intramuscular administration of cytokine-encoding plasmid vectors proved to be an effective method of cytokine delivery in these mice, and altered autoimmune disease expression.

Animals↗

Increasing Kaposi's sarcoma-associated herpesvirus seroprevalence with age in a highly Kaposi's sarcoma endemic region, Zambia in 1985.

BACKGROUND: Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is a newly discovered virus found in all forms of KS. In the United States, KSHV infection appears to be most common amongst individuals at high-risk for KS. Preliminary data from Africa suggest that KSHV infection may be much more common in the general population. OBJECTIVE: To examine the KSHV seroprevalence and age-specific patterns of infection in an African country with high rates of KS. DESIGN: Cross-sectional seroprevalence study. METHODS: Sera were taken for a hospital-based HIV seroprevalence study conducted in August 1985 in Lusaka, Zambia at a time when HIV was just becoming epidemic in this area. A total of 251 sera were randomly sampled and examined for antibodies against latent and lytic antigens to KSHV. KSHV seroprevalence was compared with demographic and clinical variables using chi2 test for linear trend and odds ratios and 95% confidence intervals. RESULTS: Overall, 58% of persons aged 14-84 years were KSHV-seropositive. KSHV seroprevalence increased linearly with age (P = 0.04) and was inversely related to years of education (P = 0.015). In contrast, HIV infection peaked in those aged 20-29 years and was positively related to years of education (P = 0.01 5). No association between KSHV and gender, marital status, or HIV serostatus was seen. CONCLUSIONS: KSHV infection was significantly more common in this region of Zambia in 1985 than it currently is in the United States. Our data are consistent with KSHV being well-established in this region prior to 1985 and that continued adult transmission of the virus was occurring. The high seroprevalence in the adolescent age-group and the relatively linear increase in prevalence with age suggest that non-sexual modes of transmission may be important for KSHV transmission in Africa.

Adolescent↗

Safely increasing the proportion of patients with community-acquired pneumonia treated as outpatients: an interventional trial.

BACKGROUND: Patients with community-acquired pneumonia who are at low risk for short-term mortality can be identified using a validated prediction rule, the Pneumonia Severity Index. Such patients should be candidates for outpatient treatment, yet many are hospitalized. OBJECTIVE: To assess a program to safely increase the proportion of low-risk patients with pneumonia treated at home. METHODS: The intervention provided physicians with the Pneumonia Severity Index score and corresponding mortality risk for eligible patients and offered enhanced visiting nurse services and the antibiotic clarithromycin. Prospectively enrolled, consecutive low-risk patients with pneumonia presenting to an emergency department during the intervention period (n = 166) were compared with consecutive retrospective controls (n = 147) identified during the prior year. A second group of 208 patients from the study hospital who participated in the Pneumonia Patient Outcomes Research Team cohort study served as controls for patient-reported measures of recovery. RESULTS: There were no significant baseline differences between patients in the intervention and control groups. The percentage initially treated as outpatients increased from 42% in the control period to 57% in the intervention period (36% relative increase; 95% confidence interval, 8%-72%; P = .01). However, more outpatients during the intervention period were subsequently admitted to the study hospital (9% vs 0%). When any admission to the study hospital within 4 weeks of presentation was considered, there was a trend toward more patients receiving all their care as outpatients in the intervention group (42% vs 52%; 25% relative increase; 95% confidence interval -2% to 59%; P = .07). No patient in the intervention group died in the 4-week follow-up period. Symptom resolution and functional status were not diminished. Satisfaction with overall care was similar, but patients treated in the outpatient setting during the intervention were less frequently satisfied with the initial treatment location than comparable control patients (71% vs 90%; P = .04). CONCLUSIONS: Use of a risk-based algorithm coupled with enhanced outpatient services effectively identified low-risk patients with community-acquired pneumonia in the emergency department and safely increased the proportion initially treated as outpatients. Outpatients in the intervention group were more likely to be subsequently admitted than were controls, lessening the net impact of the intervention.

Adult↗

Clinical-grade functional dendritic cells from patients with multiple myeloma are not infected with Kaposi's sarcoma-associated herpesvirus.

Bone marrow dendritic cells (DC) from patients with multiple myeloma (MM) were recently reported to be infected with Kaposi's sarcoma-associated herpesvirus (KSHV). Because immunotherapy strategies using DC are very promising in this disease, we looked for KSHV DNA in clinical-grade DC generated in vitro from MM patients. Adherent apheresis cells from MM patients were maintained for 7 days in clinical-grade X-VIVO 15 culture medium supplemented with granulocyte-macrophage colony-stimulating factor, interleukin-4, or interleukin-13. Tumor necrosis factor alpha was added for the last 2 days. We obtained a cell population with a DC phenotype able to endocytose fluorescein isothiocyanate (FITC)-dextran and efficiently activate resting allogenic T lymphocytes. To detect KSHV DNA, we used polymerase chain reaction (PCR) followed by Southern blotting of PCR product with a sensitivity detecting a few copies of viral DNA. All the PCR were repeated in a blinded fashion three times, on 1 mug and 0.2 mug of genomic DNA, in two different laboratories. Clinical-grade DC from 10 (91%) of 11 patients were not infected with KSHV. The apheresis cells and the purified CD34(+) cells from the same patients were also negative. A very weak PCR band was detected with DC from one patient, but the initial apheresis cells were negative. The detection of KSHV infection in 1 (9%) of 11 MM patients probably represents background seroprevalence. It seems likely that functional and clinical-grade DC from MM patients can safely be used in clinical trials.

Blood Component Removal↗

Structure and ligand binding determinants of the recombinant kringle 5 domain of human plasminogen.

The X-ray crystal structure of the recombinant (r) kringle 5 domain of human plasminogen (K5HPg) has been solved by molecular replacement methods using K1HPg as a model and refined at 1.7 A resolution to an R factor of 16.6%. The asymmetric unit of K5HPg is composed of two molecules related by a noncrystallographic 2-fold rotation axis approximately parallel to the z-direction. The lysine binding site (LBS) is defined by the regions His33-Thr37, Pro54-Val58, Pro61-Tyr64, and Leu71-Tyr74 and is occupied in the apo-form by water molecules. A unique feature of the LBS of apo-K5HPg is the substitution by Leu71 for the basic amino acid, arginine, that in other kringle polypeptides forms the donor cationic center for the carboxylate group of omega-amino acid ligands. While wild-type (wt) r-K5HPg interacted weakly with these types of ligands, replacement by site-directed mutagenesis of Leu71 by arginine led to substantially increased affinity of the ligands for the LBS of K5HPg. As a result, binding of omega-amino acids to this mutant kringle (r-K5HPg[L71R]) was restored to levels displayed by the companion much stronger affinity HPg kringles, K1HPg and K4HPg. Correspondingly, alkylamine binding to r-K5HPg[L71R] was considerably attenuated from that shown by wtr-K5HPg. Thus, employing a rational design strategy based on the crystal structure of K5HPg, successful remodeling of the LBS has been accomplished, and has resulted in the conversion of a weak ligand binding kringle to one that possesses an affinity for omega-amino acids that is similar to K1HPg and K4HPg.

Amino Acid Sequence↗

Establishing a KSHV+ cell line (BCP-1) from peripheral blood and characterizing its growth in Nod/SCID mice.

Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) sequences are present in primary effusion lymphomas (PEL). KSHV+ cell lines have been established from such lymphomas. Here we report the first description of the establishment of a KSHV+, EBV- cell line (BCP-1) from the peripheral blood of a patient with PEL. Using this cell line and a KSHV+, EBV+ PEL cell line (HBL-6) previously established from ascitic fluid, we investigated whether in nonobese diabetic/severe combined immunodeficiency disease (Nod/SCID) mice tumors representing PEL can be established. When injected intravenously (IV) into Nod/SCID mice, BCP-1 and HBL-6 infiltrated organs, with only occasional macroscopic tumor formation. Intraperitoneal injections (ip) led to the development of ascites and diffuse infiltration of organs, without obviously solid lymphoma formation, resembling the diffuse nature of human PEL. To investigate a possible mechanism for the peculiar phenotype of PEL, we examine the presence of adhesion molecules and homing markers on PEL cells before and after growing in mice. Both BCP-1 and HBL-6 cells lack expression of important cytoadhesion molecules including CD11a and CD18 (LFA1 alpha and beta chains), CD29, CD31, CD44, CD54 (ICAM-1), and CD62L and E (L and E selectins).

Animals↗

Detecting human bladder carcinoma cells in voided urine samples by assaying for the presence of telomerase activity.

BACKGROUND: In an attempt to find a more sensitive and specific noninvasive assay for the detection of bladder carcinoma, the authors assayed exfoliated cells from patients' voided urine for the presence of telomerase, an enzyme that maintains a cell's chromosomal length and is thought to be active in the transformation of normal somatic cells into immortal human tumor cells. METHODS: The authors used a polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay to determine the presence of telomerase activity in voided urine samples from patients with known but yet untreated bladder carcinoma (n = 104) and from patients with hematuria of benign causes (n = 47). For 88 of the patients with bladder carcinoma, cytology was determined independently of the telomerase results or the pathology findings. RESULTS: Of the 104 bladder carcinoma specimens, 88 (85%) tested positive for the presence of telomerase. Seventy-nine percent (23 of 29) of the Grade 1 tumors, 84% (32 of 38) of the Grade 2 tumors, and 87.5% (28 of 32) of the Grade 3 tumors were positive for telomerase activity. Five patients with carcinoma in situ (100%) were also positive. Telomerase activity was not found in 31 of 47 patients with bladder calculi, benign urethral stricture, benign prostatic hyperplasia, or inflammation. In the 16 patients (34%) who did have a false-positive result when tested for telomerase, all had either chronic or severe inflammation, including 1 patient with an inverted papilloma, 1 patient with cystitis cystica, and 1 patient with cystitis glandularis. However, for 35 normal, healthy volunteers whose voided urine samples were also assayed for the presence of telomerase activity, none was found. By comparison, only 51% (45 of 88) of the cytology samples from patients with bladder carcinoma yielded positive findings, whereas 49% (43 of 88) resulted in false-negative readings for tumors. Only 13% (3 of 23) of the Grade 1 tumors, 44% (14 of 32) of the Grade 2 tumors, and 82% (23 of 28) of the Grade 3 tumors were diagnosed by cytology. All five patients with carcinoma in situ were positive for cytology as well as for telomerase activity. When cytology was compared with the PCR-based telomerase assay in determining the presence of bladder carcinoma, the difference in the overall detection rates (85% for telomerase vs. 51% for cytology) was significant (P < 0.001). Furthermore, when telomerase activity was compared with cytology for low grade lesions (Grades 1 and 2), the difference in the detection rates (82% for telomerase vs. 31% for cytology) was also significant (P < 0.001). CONCLUSIONS: Urinary cytology yields poor results for low grade tumors. This study shows the possible application of the telomerase assay in detecting bladder carcinoma, in particular low grade tumors, in voided urine samples.

Adult↗

Nasopharyngeal swab and PCR for the screening of nasopharyngeal carcinoma in the endemic area: a good supplement to the serologic screening.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common head and neck cancer in Taiwan. Early detection is the best way to improve survival for this disease. A prospective study was designed to assess the feasibility of a new screening method for NPC by use of polymerase chain reaction (PCR) based on the close association of NPC and Epstein-Barr virus (EBV). METHODS: One hundred thirty-three different tissues from nasopharynx, nose, and sinus were investigated by use of PCR to check for the presence of EBV genome. Subsequently, from April 1996 to March 1997, 55 patients were enrolled in a prospective screening study. All patients underwent nasopharyngeal swabs before biopsy. Polymerase chain reaction detection of EBV genome was conducted on swab samples. Anti-EBV viral capsid antigen (VCA) in IgA and IgG class were checked at the same visit. RESULTS: The EBV genome was present in 91.4% (85/93) of NPC tissues and in 25.0% (10/40) of non-NPC tissues (p < .001, chi2 test). Of the 55 swabs, 49 (89.1%) specimens obtained enough cells for PCR examination. Thirty of these 49 patients were pathologically proved NPC. The presence of EBV were 86.7% (26/30) in NPC group and 42.1% (8/19) in non-NPC group. The sensitivity and specificity were 86.7% and 57.9%, respectively, which were similar to those of serologic method (87.5% and 43.5%) when the cut-off point was set at anti-VCA IgG > or = 160 and IgA > or = 10. Combining both methods elevates the specificity to 84.2%. CONCLUSIONS: The sensitivity of this PCR screening method is similar to that of the serologic method. Combining both methods can greatly increase the specificity, indicating this new method is a good supplement to the serologic screening of this endemic disease.

Antibodies, Viral↗

Metabolic detriment in donor heart valves induced by ischemia and cryopreservation.

BACKGROUND: The injury resulting from postmortem ischemia is a critical deterrent to the availability of donor valves. Using the reduction of XTT-tetrazolium salt as a marker of metabolic sequelae, we assessed the injurious effect of ischemia and the metabolic sequelae in 156 porcine semilunar leaflets. METHODS: The leaflets were randomly allocated to noncryoprocessed (n = 72) or cryoprocessed (n = 72) groups. At each preservation temperature of 4 degrees C, 24 degrees C, or 37 degrees C, 24 leaflets each were exposed to one of four storage periods of 9, 17, 30, or 60 hours. Twelve fresh aortic leaflets served as baseline reference samples. RESULTS: There was a progressive loss in the metabolic functioning of valve leaflet cells in both noncryopreserved and cryopreserved tissue as the storage times increased. Cryopreserved tissue showed a greater loss of function than noncryopreserved tissue did. The metabolic injury was mainly a consequence of cryoprocessing. The greatest loss in metabolic functioning occurred in the valves stored for 60 hours. The least favorable combination of variables was cryopreservation and a precryopreservation storage time of 60 hours. CONCLUSIONS: We conclude that 30- to 60-hour delays do not have a significant metabolic effect on cardiac leaflets. Thus it may be possible to safely extend the permissible ischemic periods after organ harvest.

Animals↗

Heparinization on pericardial substitutes can reduce adhesion and epicardial inflammation in the dog.

OBJECTIVE: Primary concerns about currently available pericardial substitutes include adhesion and epicardial reaction. The purpose of this study is to evaluate host reaction to pericardial substitutes with and without incorporating slow heparin release. METHODS: To avoid biologic variation among these pericardial patches, we made a composite of six membranes. The composite membrane consisted of epoxy-fixed patches with (1) or without (2) ionically bound heparin, a glutaraldehyde-fixed patch with (3) or without (4) ionically bound heparin, an expanded polytetrafluoroethylene patch (5), and a polyester polymeric patch (6). Ten recipient dogs weighing from 12 to 19 kg (mean 13.6 kg) were used to assess the composite membranes as pericardial substitutes. The implanted composite membranes were retrieved 1 week (one dog), 2 weeks (one dog), 4 weeks (one dog), 8 weeks (one dog), and 12 weeks (six dogs) after implantation. RESULTS: Overall, the synthetic patches had a more notable inflammatory reaction than the biologic patches with or without ionically bound heparin. The heparin-bound patches caused significantly less inflammation than their nonheparinized counterparts. The heparinized porcine patches cross-linked with different compounds were found to have less fibrous formation than the nonheparinized patches and the synthetic patches. CONCLUSIONS: Heparinized pericardial substitutes may cause less adhesion and inflammatory reaction than nonheparinized material.

Animals↗

Sensitivity and specificity of NMP-22, telomerase, and BTA in the detection of human bladder cancer.

OBJECTIVES: The recent introduction of novel molecular markers into clinical urology has created a need to evaluate the efficacy and utility of these potential markers. The ideal assay for bladder cancer should be noninvasive, sensitive, specific, and cost-effective. We compared the Matritech nuclear maxtrix protein (NMP)-22 assay, telomerase activity, and the Bard bladder tumor antigen (BTA) assay for the detection of human bladder cancer. METHODS: A single voided urine sample was obtained from patients with hematuria without bladder cancer and from patients with known bladder cancer before any treatment. Approximately 50 to 100 mL of voided urine sample was collected and aliquotted for the various assays. The results were compared to single cytologic results and ultimately to pathologic findings. RESULTS: In 47 patients with bladder cancer, the overall sensitivity was 81% for NMP-22, 80% for telomerase, 40% for BTA, and 40% for cytology. For Ta tumors (n = 31), sensitivity was 81% for NMP-22, 70% for telomerase, 32% for BTA, and 26% for cytology. For T1 or higher stage tumors (n = 13), sensitivity was 82% for NMP-22, 91% for telomerase, 64% for BTA, and 64% for cytology. The remaining 3 patients had carcinoma in situ (CIS). When tumors were stratified by tumor grade, grade I tumors (n = 16) were detected at 69% with NMP-22, 65% with telomerase, 13% with BTA, and 6% with cytology. Grade II tumors (n = 14) were detected at 86% with NMP-22, 72% with telomerase, 36% with BTA, and 36% with cytology. Grade III tumors (n = 14) were detected at 93% with NMP-22, 93% with telomerase, 79% with BTA, and 79% with cytology. Patients with CIS (n = 3) were detected at 67% with NMP-22, 100% with telomerase, 33% with BTA, and 67% with cytology. In 30 patients with hematuria but without bladder cancer, the overall specificity of the assays was 77% for NMP-22, 80% for telomerase, 73% for BTA, and 94% for cytology. CONCLUSIONS: In the population tested, NMP-22 and the telomerase assays gave similar sensitivity and specificity for the detection of bladder cancer, and appear to offer a greater sensitivity than the BTA assay and/or conventional cytology.

Aged↗

Evidence against KSHV infection in the pathogenesis of multiple myeloma.

Kaposi's sarcoma-associated herpesvirus (KSHV) is likely to play a pathogenic role in Kaposi's sarcoma, body cavity-based primary effusion lymphoma and a subset of Castleman's disease. A recent polymerase chain reaction (PCR)-based study reported an association between KSHV and multiple myeloma (MM). We searched for KSHV infection in MM patients by serology, PCR and immunohistochemistry. In addition, we cultured dendritic and stromal cells from MM patients. KSHV antibodies were universally absent from MM patients (0/25) whereas EBV antibodies were nearly ubiquitous (24/25). All of the bone marrow biopsies (0/16) and negative controls (0/4) were vIL-6 negative. None of the bone marrow aspirates (0/6) or biopsies (0/3), peripheral blood mononuclear cells (0/8), mononuclear apheresis cells (0/5) or dendritic cell cultures (0/5) were positive by PCR. One of the MM stromal cell cultures (1/7) was positive for KSHV DNA by PCR and weakly positive on direct southern hybridization using a probe to the terminal repeat region. However, this same patient was PCR negative using another primer set, KSHV seronegative, and negative for vIL-6 immunostaining. Our results suggest that the KSHV DNA positivity rate among MM patients is much lower than previously reported.

Antibodies, Viral↗

Antiviral activity of tumor-suppressor pathways: clues from molecular piracy by KSHV.

A common feature of many tumor viruses is that they possess genes that produce specific proteins to inhibit major cellular tumor-suppressor pathways. Despite intensive studies, the reasons why these diverse and unrelated viruses have independently evolved oncogenes remains obscure. Kaposi-sarcoma-associated herpesvirus (KSHV or HHV8) has pirated a number of recognizable cellular genes that are key to cell survival and proliferation. In this review, we provide an overview of the known activities of these viral genes and show that many of these pirated proteins affect the same cellular pathways targeted by other, unrelated tumor viruses. We speculate that tumor-suppressor pathways are used by the cell as a primary defense against persistent virus infection, in addition to their well-known activity in regulating cell proliferation.

Animals↗

A randomized, double-blind, dose-response study of ondansetron in the prevention of postoperative nausea and vomiting.

STUDY OBJECTIVE: To determine the dose-response relationship of ondansetron in preventing postoperative nausea and vomiting (PONV) in women undergoing elective surgery. DESIGN: Prospective, randomized, double-blind study. SETTING: University-affiliated hospital. PATIENTS: 175 women aged 18 to 80 years scheduled for elective surgery. INTERVENTIONS: One of six doses of ondansetron (0.5 mg, 1 mg, 2 mg, 4 mg, 8 mg, 16 mg) or placebo was given prior to the induction of general anesthesia with propofol. Maintenance was with nitrous oxide, isoflurane, opioid, and muscle relaxant. MEASUREMENTS AND MAIN RESULTS: The study period began when the patient emerged from anesthesia. Nausea scores were recorded on a 0 to 10 scale at multiple time points during the 24-hour study period. Patient satisfaction via a visual analog scale (VAS) was determined at 1 and 24 hours after awakening. Rescue medication was given for severe nausea, three emetic episodes within 15 minutes, or if requested by the patient. The primary efficacy variable was the need for rescue antiemetic therapy. The dose-response curve (by logistic regression) of the percentage of patients not rescued versus dose indicated an ED50 of 0.54 mg (95% confidence interval 0.03-1.05 mg). Fewer patients required rescue in the 4 mg dose group compared with lower doses. However, the difference reached significance only in comparison with the 0.5 mg dose group. Survival analysis of the need for rescue, and nausea score versus time curves, also both suggested the superiority of the 4 mg dose compared with lower doses. In addition, there was a highly significant correlation between the lack of need for rescue and satisfaction with anesthesia at 24 hours after emergence. CONCLUSION: The recommended dose of ondansetron for PONV prophylaxis in women remains 4 mg.

Adolescent↗