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G Chang

Publications and source records attributed to G Chang.

At least 19 recordsLinked to original sources
PubMed2001

Structure of MsbA from E. coli: a homolog of the multidrug resistance ATP binding cassette (ABC) transporters.

Multidrug resistance (MDR) is a serious medical problem and presents a major challenge to the treatment of disease and the development of novel therapeutics. ABC transporters that are associated with multidrug resistance (MDR-ABC transporters) translocate hydrophobic drugs and lipids from the inner to the outer leaflet of the cell membrane. To better elucidate the structural basis for the "flip-flop" mechanism of substrate movement across the lipid bilayer, we have determined the structure of the lipid flippase MsbA from Escherichia coli by x-ray crystallography to a resolution of 4.5 angstroms. MsbA is organized as a homodimer with each subunit containing six transmembrane alpha-helices and a nucleotide-binding domain. The asymmetric distribution of charged residues lining a central chamber suggests a general mechanism for the translocation of substrate by MsbA and other MDR-ABC transporters. The structure of MsbA can serve as a model for the MDR-ABC transporters that confer multidrug resistance to cancer cells and infectious microorganisms.

ATP-Binding Cassette Transporters↗
PubMed2001

Slurry sampling fluorination assisted electrothermal vaporization-inductively coupled plasma-atomic emission spectrometry for the direct determination of metal impurities in aluminium oxide ceramic powders.

A new analytical procedure for the direct determination of metal impurities (Cr, Cu, Fe and V) in aluminium oxide ceramic powders by slurry sampling fluorination assisted electrothermal vaporization-inductively coupled plasma-atomic emission spectrometry (ETV-ICP-AES) is reported. A polytetrafluoroethylene (PTFE) emulsion was used as a fluorinating reagent to promote the vaporization of impurity elements in aluminium oxide ceramic powders from the graphite tube. A vaporization stage with a long ramp time and a short hold time provided the possibility of temporal analyte-matrix separation. The experimental results indicated that a 10 microL 1% m/v slurry of aluminium oxide could be destroyed and vaporized completely with 600 micrograms PTFE under the selected conditions. Two aluminium oxide ceramic powder samples were used without any additional pretreatment. Analytical results obtained by using standard addition method with aqueous standard solution were checked by comparison of the results with pneumatic nebulization (PN)-ICP-AES based on the wet-chemical decomposition and analyte-matrix separation. The limits of detection (LODs) between 0.30 microgram g-1 (Fe) and 0.08 microgram g-1 (Cu) were achieved, and, the repeatability of measurements was mainly better than 10%.

Aluminum Oxide↗
PubMed2001

Malakoplakia involving the abdominal wall, urinary bladder, vagina, and vulva: case report and discussion of malakoplakia-associated bacteria.

A 29-year-old woman presented with a 3-month history of multiple purulent discharging nodules involving her lower abdomen, vulva, and left thigh. Physical examination also disclosed vaginal nodules and a left pelvic mass. Cystoscopy revealed multiple mucosal nodules and a perforation of the left vesical wall that appeared to communicate with the pelvic mass. Biopsies of the vesical and vulvar nodules revealed malakoplakia. Surgery and antibiotic therapy resulted in regression of all the lesions.

Abdominal Muscles↗
PubMed2001

Alcohol-screening instruments for pregnant women.

According to new studies, even low levels of prenatal alcohol exposure can negatively affect the developing fetus, thereby increasing the importance of identifying women who drink during pregnancy. In response, researchers have developed several simple alcohol-screening instruments for use with pregnant women. These instruments, which can be administered quickly and easily, have been evaluated and found to be effective. Because of the potential adverse consequences of prenatal alcohol exposure, short screening questionnaires are worthwhile preventive measures when combined with appropriate followup.

Alcohol Drinking↗
PubMed2001

[A controlled clinical study between hepatic arterial infusion with embolized curcuma aromatic oil and chemical drugs in treating primary liver cancer].

OBJECTIVE: To evaluate the effectiveness, toxicity and prospective application of hepatic arterial infusion (HAI) with Embolized Curcuma Aromatic oil (CAO) in treating primary liver cancer (PLC). METHODS: In the treated group, 32 patients with PLC were treated by HAI with 1-3 ml of embolized CAO and oral administration of Chinese herbal medicine. In the control group, 32 patients with PLC were treated with transcatheter artery chemoembolization (TACE). RESULTS: In the treated group, one patient attained complete remission (CR) and 13 partial remission (PR), the total effective rate being 43.75%. The level of alpha fetal protein (AFP) turned to normal range in 7 cases and decreased in other 7. In the control group, 10 obtained PR and the total effective rate being 31.25%, AFP level turned to normal in 5 and decreased in 2. There was no statistical significance between the two groups. The incidences of post-embolism syndrome, such as fever, abdominal pain and vomiting were similar between the two groups but no myelosuppression occurred in the treated group with significant difference (P < 0.01) as comparing with that in the control group. The mean survival time, median survival time, 1-, 2- and 3-year survival rate in the treated group was 11.5 months, 10 months, 37.5%, 13.3% and 6.9% respectively, while in the control group was 7.25 months, 6 months, 15.6%, 3.2% and 0 respectively. The treated group was better in mean survival time, median survival time and 1-year survival rate than that of the control group (P < 0.05). CONCLUSION: HAI with embolized CAO showed a similar favorite effect in treating PLC as that of TACE, but superior than TACE with longer survival time and milder myelosuppression.

Adult↗
PubMed2000

Hemodynamic effects of sildenafil in men with severe coronary artery disease.

BACKGROUND: The cardiovascular effects of sildenafil are important because of the frequent presence of underlying cardiac disease in men with erectile dysfunction and reports indicating serious cardiac events temporally associated with the use of this drug. METHODS: We assessed the systemic, pulmonary, and coronary hemodynamic effects of oral sildenafil (100 mg) in 14 men (mean [+/-SD] age, 61+/-11 years) with severe stenosis of at least one coronary artery (stenosis of >70 percent of the vessel diameter) who were scheduled to undergo percutaneous coronary revascularization. Blood-flow velocity and flow reserve were assessed with a Doppler guidewire in 25 coronary arteries, including 13 severely diseased arteries (mean stenosis, 78+/-7 percent) and 12 arteries without stenosis, used as a reference; maximal hyperemia was induced (to assess flow reserve) with the intracoronary administration of adenosine both before and after sildenafil. RESULTS: Oral sildenafil produced only small decreases (<10 percent) in systemic arterial and pulmonary arterial pressures, and it had no effect on pulmonary-capillary wedge pressure, right atrial pressure, heart rate, or cardiac output. There were no significant changes in average peak coronary flow velocity, coronary-artery diameter, volumetric coronary blood flow, or coronary vascular resistance. Coronary flow reserve at base line was lower in the stenosed arteries (1.26+/-0.26) than in the reference arteries (2.19+/-0.44) and increased about 13 percent in both groups of arteries combined after the administration of sildenafil (from 1.70+/-0.59 to 1.92+/-0.72, P=0.003). The ratio of coronary flow reserve in coronary arteries with stenosis to that in the reference arteries (0.57+/-0.14) was not affected by sildenafil. CONCLUSIONS: No adverse cardiovascular effects of oral sildenafil were detected in men with severe coronary artery disease.

Coronary Disease↗
PubMed2000

Selective use of tube cholecystostomy with interval laparoscopic cholecystectomy in acute cholecystitis.

HYPOTHESIS: Tube cholecystostomy followed by interval laparoscopic cholecystectomy is a sale and efficacious treatment option in critically ill patients with acute cholecystitis. DESIGN: Retrospective cohort study within a 4 1/2%-year period. SETTING: University hospital. PATIENTS: Of 324 patients who underwent laparoscopic cholecystectomy, 65 (20%) had acute cholecystitis; 15 of these 65 patients (mean age, 75 years) underwent tube cholecystostomy. INTERVENTION: Thirteen patients at high risk for general anesthesia because of underlying medical conditions underwent percutaneous tube cholecystostomy with local anesthesia. Laparoscopic tube cholecystostomy was performed on 2 patients during attempted laparoscopic cholecystectomy because of severe inflammation. Interval laparoscopic cholecystectomy was attempted after an average of 12 weeks. MAIN OUTCOME MEASURES: Technical details and clinical outcome. RESULTS: Prompt clinical response was observed in 13 (87%) of the patients after tube cholecystostomy. Twelve patients (80%) underwent interval cholecystectomy. Laparoscopic cholecystectomy was attempted in 11 patients and was successful in 10 (91%), with 1 conversion to open cholecystectomy. One patient had interval open cholecystectomy during definitive operation for esophageal cancer and another had emergency open cholecystectomy due to tube dislodgment. Two patients (13%) had complications related to tube cholecystostomy and 2 patients died from sepsis before interval operation. One patient died from sepsis after combined esophagectomy and cholecystectomy. Postoperative minor complications developed in 2 patients. At a mean follow-up of 16.7 months (range, 0.5-53 months), all patients were free of biliary symptoms. CONCLUSIONS: Tube cholecystostomy allowed for resolution of sepsis and delay of definitive surgery in selected patients. Interval laparoscopic cholecystectomy was safely performed once sepsis and acute infection had resolved in this patient group at high risk for general anesthesia and conversion to open cholecystectomy. Just as catheter drainage of acute infection with interval appendectomy is accepted in patients with periappendiceal abscess, tube cholecystostomy with interval laparoscopic cholecystectomy should have a role in the management of selected patients with acute cholecystitis.

Acute Disease↗
PubMed2000

Changes in lipoprotein(a) concentration after orthotopic heart transplantation.

BACKGROUND: Elevated concentrations of lipoprotein(a) have been considered an important risk factor in the development of premature cardiovascular disease and have been proposed as a risk factor in the development of accelerated cardiac allograft vasculopathy after orthotopic heart transplantation. METHODS: We prospectively measured lipoprotein(a), fasting cholesterol, and triglyceride concentrations before (n = 38), 6 months (n = 38), and 1 year (n = 21) after orthotopic heart transplantation. The mean age of the patients was 52 +/- 2 years. Eighty-seven percent of the patients were men, 82% were white, and 61% had ischemic cardiomyopathy. RESULTS: Mean lipoprotein(a) concentration was lower 6 months after transplantation than it was before the operation (23 +/- 3 mg/dL vs 17 +/- 3 mg/dL; P =.014) and remained low 1 year after transplantation (23 +/- 3 mg/dL vs 18 +/- 4 mg/dL; P = not significant). In contrast, mean cholesterol concentration was higher 6 months after transplantation (171 +/- 8 mg/dL vs 221 +/- 8 mg/dL; P <.001) and 1 year (171 +/- 8 mg/dL vs 205 +/- 10 mg/dL; P <.01) than it was before transplantation. Triglyceride concentration was higher 1 year after transplantation than it was before the operation (146 +/- 13 mg/dL vs 184 +/- 20 mg/dL; P =.017). CONCLUSIONS: Lipoprotein(a) concentrations decrease during the 6 months after transplantation and stay low for at least 1 year after the operation. Additional studies are needed to ascertain the effect these changes in lipoprotein(a) concentration on the development of cardiac allograft vasculopathy.

Adolescent↗
PubMed2000

A brief intervention for prenatal alcohol use: an in-depth look.

About 20% of pregnant women will drink alcohol, even though no universally safe level of prenatal alcohol consumption has been established. This study of 123 alcohol screen-positive pregnant women receiving a brief intervention in the 16th week of gestation examines the relationship of drinking goals, reasons for the goals, recognition of situations increasing risk of drinking, and subsequent antepartum consumption. While women who named abstinence as their antepartum drinking goal were more likely not to be consuming alcohol at the time of study enrollment (chi(2) = 16.80, df = 1, p =.001), current drinkers who named abstinence as their goal did reduce subsequent prenatal alcohol use (chi(2) = 10.04, df = 1, p =.002). All current drinkers who indicated fetal alcohol syndrome as a reason not to drink reduced their subsequent alcohol consumption (chi(2) = 11.04, df = 1, p =.001). Future efforts may include the partners and support systems of pregnant women in education or intervention programs to reduce prenatal alcohol consumption to enhance their effectiveness.

Adult↗
PubMed2000

[The effect of pentoxifylline on endotoxin-induced biopterin formation in rabbits].

OBJECTIVE: To observe the potential effect of pentoxifylline on endotoxin-mediated biopterin (tetrahydrobiopterin and more oxidized species) formation and systemic hemodynamics. METHODS: Rabbits were subjected to endotoxic shock induced by a bolus intravenous injection of E. coli O26B6 lipopolysaccharide (400 microg/kg). 28 animals were divided into sham-operation group (n = 8), endotoxic shock group (n = 10), and pentoxifylline-treated group (n = 10). Plasma biopterin and tumor necrosis factor-alpha (TNF) levels, and guanosine triphosphate cyclohydrolase I (GTP-CHI) activity in tissues were determined at various intervals. RESULTS: Treatment with pentoxifylline significantly decreased plasma biopterin and TNF levels at 2 to 8 hours after endotoxin challenge (P < 0.05, P < 0.01), and inhibited GTP-CHI activities in the liver, lung, and myocardial tissues (P < 0.05). Meanwhile, systemic hemodynamic parameters, including mean arterial pressure, cardiac output, and total peripheral resistance, in the treatment group were much higher than those in the endotoxic shock group. CONCLUSIONS: These data suggest that early treatment with pentoxifylline can effectively inhibit endotoxin-induced biopterin synthesis and release, and markedly improve systemic hemodynamics during septic shock.

Animals↗
PubMed1999

Biomechanical properties of muscle-tendon unit under high-speed passive stretch.

OBJECTIVE: The purpose of this study was to investigate the strain injury mechanisms of the Achilles muscle-tendon unit during high-speed passive stretch. DESIGN: The high-speed traction device consisted of an impactor which dropped freely to hit one end of a lever, transferring the impact energy to traction energy at the other end. A muscle-tendon unit was attached to the other end of the lever via a force link, and the elongation was recorded with a high-speed camera. BACKGROUND: The muscle-tendon unit is thought to act viscoelastically. It is generally strain rate dependent, exhibiting higher tensile stress at faster strain rates. However, previous studies of passive stretch in muscle-tendon units usually employed low strain rates. METHODS: 16 fresh Achilles muscle-tendon units were subjected to passive stretch at a test speed of 310 cm s(-1). The history of elongation and the traction force of the muscle-tendon unit during the elongation process were analyzed. RESULTS: The muscle-tendon units exhibited highly nonlinear mechanical behavior. Most of the elongation occurred in muscle and resulted in structural failure. Failure was not found in the tendon or muscle-tendon junction. Muscle fibers during stretching reached their maximum mechanical strength and then progressively ruptured. CONCLUSION: The strain rate is an important factor in strain injuries of the muscle-tendon unit due to passive stretch. The muscle is a good energy absorber; the rupture process can absorb a great deal of external energy and prevent complete failure of the muscle, while also protecting bone and joints. RELEVANCE: The study of muscle-tendon unit under high-speed stretch could help us to understand the mechanism of strain injuries over passive stretch in real-life situations.

Achilles Tendon↗
PubMed1999

'Feeling the pressure': structural insights into a gated mechanosensitive channel.

The structure determination of the large-conductance mechanosensitive channel (MscL) from Mycobacterium tuberculosis has revealed the architecture of the first full-length, gated pentameric ion channel. This structure provides insights into the elements participating in the conductance and gating mechanisms of these channels.

Amino Acid Sequence↗
PubMed1999

Brief intervention for alcohol use in pregnancy: a randomized trial.

AIMS: To assess the impact of a brief intervention on antepartum alcohol consumption. DESIGN: A randomized clinical trial. SETTING: The obstetrics practices of the Brigham and Women's Hospital in Boston, MA, USA. PARTICIPANTS: Two hundred and fifty eligible women initiating prenatal care. INTERVENTION: A comprehensive assessment of alcohol use (assessment only, AO) or the same comprehensive assessment with a brief intervention (BI). MEASUREMENT: Demographic background and obstetric history of subjects, current and lifetime use of alcohol and substances, composite Addiction Severity Index scores, and antepartum alcohol use. FINDINGS: Of the 250, 247 (99%) subjects provided information on their antepartum drinking. Both the AO and BI groups had reductions in antepartum alcohol consumption, but differences in reductions by group were not statistically significant (p > 0.05). Risk of antepartum drinking after either the AO or BI was increased nearly threefold if the subject had any prenatal alcohol consumption before assessment (p = 0.0001). For the 143 subjects who were abstinent pre-assessment, however, those who received the BI maintained higher rates of abstinence (86% versus 72%, p = 0.04). CONCLUSIONS: After a comprehensive assessment of alcohol use, subjects in both the AO and BI groups reduced their antepartum alcohol consumption. The importance of screening for prenatal alcohol use is underscored by the findings that any prenatal alcohol consumption increases the risk of continued antepartum drinking.

Adolescent↗
PubMed1999

Identifying prenatal alcohol use: screening instruments versus clinical predictors.

The purpose of this study is to compare the accuracy of screening instruments with clinical predictors in the identification of prenatal alcohol use. 350 women initiating prenatal care at the Brigham and Women's Hospital (Boston, MA) completed the T-ACE, AUDIT, and SMAST. The predictive accuracy of each was compared using Receiver Operating Characteristic (ROC) curve analysis. The T-ACE, AUDIT, and clinical predictors alone correctly identified 65 to 70% of current drinkers, whereas the SMAST alone performed only slightly better than chance. The predictive ability of the T-ACE was further improved with the addition of clinical predictors.

Adult↗
PubMed1999

ELISA is the superior method for detecting antineutrophil cytoplasmic antibodies in the diagnosis of systemic necrotising vasculitis.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) have been used as a diagnostic marker for systemic necrotising vasculitis, a disease classification which includes Wegener granulomatosis, microscopic and classic polyarteritis nodosa, and Churg Strauss disease. OBJECTIVE: To compare the diagnostic value of the two methods for detecting these antibodies--immunofluorescence and enzyme linked immunosorbent assay (ELISA)--with respect to biopsy proven active systemic necrotising vasculitis in a clinically relevant population. METHODS: A prospective study to ascertain the patient's diagnosis at the time of each of the 466 requests for ANCA received at one laboratory over a nine month period, and allocate each to one of five diagnostic groups: active and inactive biopsy proven systemic necrotising vasculitis, suspected systemic necrotising vasculitis, low probability systemic necrotising vasculitis, and not systemic necrotising vasculitis. RESULTS: ELISA was superior to immunofluorescence in the diagnosis of systemic necrotising vasculitis because it was less likely to detect other diseases. This was reflected in its specificity of 97% and positive predictive value of 73%, compared with 90% and only 50% for immunofluorescence (p = 0.0006 and p = 0.013, respectively). ELISA had a negative predictive value of 98% which was not significantly different to immunofluorescence. ELISA was technically superior. CONCLUSIONS: ELISA is the superior method of ANCA detection in the diagnosis of systemic necrotising vasculitis and should be used in conjunction with a compatible clinical picture and histological evidence.

Adolescent↗
PubMed1999

Heterozygous germline ATM mutations do not contribute to radiation-associated malignancies after Hodgkin's disease.

PURPOSE: The successful treatment of Hodgkin's disease has been associated with an increased incidence of secondary malignancies. To investigate whether genetic factors contribute to the development of secondary tumors, we collected family cancer histories and performed mutational analysis of the ataxia-telangiectasia (AT) gene, ATM, in a cohort of Hodgkin's disease survivors with secondary malignancies. ATM was chosen for evaluation because of the increased radiosensitivity of cells derived from AT patients and obligate heterozygotes and the epidemiologic observation that AT carriers are at increased risk for radiation-induced breast cancer. PATIENTS AND METHODS: Fifty-two patients who developed one or more neoplasms after treatment for Hodgkin's disease participated in this study. Personal and family histories of cancer were obtained through patient interviews and review of medical records. ATM mutational analysis was performed using a yeast-based protein truncation assay. RESULTS: Seventy-six secondary neoplasms were observed in this cohort of 52 Hodgkin's disease survivors, with 18 patients (35%) developing more than one secondary neoplasm. Positive family histories of cancer were present in 11 (21%) of 52 patients, compared with three (4%) of 68 Hodgkin's disease patients in a comparison cohort who did not develop secondary neoplasms (P =.008; Fisher's exact test). No germline ATM mutations were identified, resulting in an estimated AT carrier frequency in this population of 0% (90% confidence interval, 0% to 4%). CONCLUSION: Analysis of the number of tumors per individual and the family history of cancer in our cohort suggests that genetic factors may contribute to development of secondary neoplasms in a subset of Hodgkin's disease survivors. Mutational analysis, however, does not support a significant role for heterozygous truncating ATM mutations. Future studies evaluating other genes involved in DNA damage response pathways are warranted.

Adolescent↗
PubMed1999

The TWEAK: application in a prenatal setting.

OBJECTIVE: The TWEAK is a screening instrument used to identify women who are risk drinkers. Potential limitations of previous studies of the TWEAK in the prenatal setting include indirect administration of the instrument to minority, indigent pregnant women. The purpose of this study is to assess the efficacy of the TWEAK when it is given directly to a sample of pregnant women of different socioeconomic backgrounds. METHOD: The original TWEAK, with two different tolerance questions, was administered to a sample of 135 pregnant women enrolled in a study of alcohol use during pregnancy at the obstetrics practices of the Brigham and Women's Hospital in Boston, Massachusetts. RESULTS: The TWEAK, using the first tolerance question (number of drinks before feeling the first effects of alcohol) with the cut point set at more than two drinks, had the best predictive ability for lifetime alcohol diagnoses and risk drinking. The sensitivity of the TWEAK can be increased if the cut point for the first tolerance question is set at two drinks, with some loss of specificity and predictive ability. Medical record assessment was the least sensitive but most specific method of identifying alcohol use by pregnant women. CONCLUSIONS: The TWEAK has promise as a screening instrument for identifying risk drinking during pregnancy. Future work should include testing in other clinical populations.

Alcohol Drinking↗