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Biomedical subjects

H Chang

Publications and source records attributed to H Chang.

At least 181 records · Page 10Linked to original sources
PubMed1994

Ion permeation properties of the glutamate receptor channel in cultured embryonic Drosophila myotubes.

Ion permeation properties of the glutamate receptor channel in cultured myotubes of Drosophila embryos were studied using the inside-out configuration of the patch-clamp technique. Lowering the NaCl concentration in the bath (intracellular solution), while maintaining that of the external solution constant, caused a shift of the reversal potential in the positive direction, thus indicating a higher permeability of the channel to Na+ than to Cl- (PCl/PNa < 0.04), and suggesting that the channel is cation selective. With 145 mM Na+ on both sides of the membrane, the single-channel current-voltage relation was almost linear in the voltage range between -80 and +80 mV, the conductance showing some variability in the range between 140 and 170 pS. All monovalent alkali cations tested, as well as NH4+, permeated the channel effectively. Using the Goldman-Hodgkin-Katz equation for the reversal potential, the permeability ratios with respect to Na+ were estimated to be: 1.32 for K+, 1.18 for NH4+, 1.15 for Rb+, 1.09 for Cs+, and 0.57 for Li+. Divalent cations, i.e. Mg2+ and Ca2+, in the external solution depressed not only the inward but also the outward Na+ currents, although reversal potential measurements indicated that both ions have considerably higher permeabilities than Na+ (PMg/PNa = 2.31; PCa/PNa = 9.55). The conductance-activity relation for Na+ was described by a hyperbolic curve. The maximal conductance was about 195 pS and the half-saturating activity 45 mM. This result suggests that Na+ ions bind to sites in the channel. All data were fitted by a model based on the Eyring's reaction rate theory, in which the receptor channel is a one-ion pore with three energy barriers and two internal sites.

Animals↗
PubMed1994

Alterations of p53 and c-myc in the clonal evolution of malignant lymphoma.

We derived the lymphoma cell lines OCI-Ly 13.1 and OCI-Ly 13.2 from a patient with non-Hodgkin's lymphoma at the time of presentation and during chemotherapy-resistant relapse. These lines were of T-cell phenotype and contained the identical T-cell receptor beta-chain rearrangement, indicating that both lines were members of the same malignant clone. The lines differed in their growth characteristics; OCI-Ly 13.1 grew slowly and required growth factors for colony formation, whereas OCI-Ly 13.2 grew rapidly and formed colonies without addition of growth factors. To test whether or not these biologic differences were associated with specific genetic changes, we evaluated the status of the c-myc and p53 genes of both cell lines. The p53 and c-myc genes of OCI-Ly 13.1 were in germline configuration and produced normal-sized transcripts. The p53 protein expressed in OCI-Ly 13.1 was recognized by the anti-p53 monoclonal antibody, PAb240, indicating a conformation typical of p53 proteins expressed by p53 alleles containing a missense mutation. However, sequencing studies of the entire p53 coding region did not reveal any point mutations. In contrast, the cell line OCI-Ly 13.2 contained structural abnormalities of both the c-myc and p53 genes. In addition, one of the p53 alleles was lost as determined by a cDNA probe for the p53 gene (17p 13.1) and the YNZ22.1 probe (17p 13.3). These changes resulted in the absence of p53 protein and mRNA in OCI-Ly 13.2 as detected by immunoprecipitation and Northern blot analysis, respectively. They may be a reflection of disease progression and may be associated with the altered behavior of the malignant cell population within the patient and in vitro.

Base Sequence↗
PubMed1994

Systemic and diaphragmatic oxygen delivery-consumption relationships during hemorrhage.

When tissue O2 delivery falls below a critical threshold, tissue O2 uptake (VO2) becomes limited. We compared critical O2 delivery and critical and maximum O2 extraction ratios of the resting and contracting left hemidiaphragm with those of nondiaphragmatic tissues in seven dogs. The left hemidiaphragm was perfused through the left inferior phrenic artery with blood from the left femoral artery. Phrenic venous blood was sampled through a catheter in the inferior phrenic vein. Systemic O2 delivery was reduced in stages by controlled hemorrhage. Left diaphragmatic VO2 during rest and during 3 min of continuous stimulation (3 Hz) of the left phrenic nerve and VO2 of the remaining nonleft hemidiaphragmatic tissues were measured at each stage. Critical diaphragmatic O2 delivery for the resting diaphragm averaged 0.8 +/- 0.16 ml.min-1.100 g-1 with a critical O2 extraction ratio of 65.5 +/- 6%. In the contracting diaphragm, they averaged 5.1 +/- 0.9 ml.min-1.100 g-1 and 81 +/- 5%, respectively. Whole body O2 delivery at which resting diaphragmatic VO2 became supply limited was similar to that for nondiaphragmatic tissues. By comparison, supply limitation of VO2 occurred at a higher systemic O2 delivery in the contracting diaphragm than in the rest of the body despite the increase in critical diaphragmatic extraction ratio. Thus, oxygenation of the isolated diaphragm does not appear to be preferentially preserved during generalized reductions in O2 delivery. These results suggest that, in diseases associated with increased work of breathing and decreased O2 delivery, the diaphragm may become metabolically impaired before limitation of VO2 is observed systemically.

Animals↗
PubMed1994

Clinical implications and factors related to left atrial spontaneous echo contrast in chronic nonvalvular atrial fibrillation.

The mechanisms leading to formation of spontaneous echo contrast (SEC), a smoke-like echo on echocardiography, are still controversial. To further explore the clinical implications and factors related to SEC formation, the correlation among echocardiographic variables, hematologic parameters or platelet aggregability, and the occurrence of SEC was studied in 119 patients with chronic nonvalvular atrial fibrillation. There were 75 men and 44 women with a mean age of 65 +/- 10 years (range 38-88). Left atrial SEC was detected in 39 patients (33%) by transesophageal echocardiography. Patients with history of systemic embolism were more frequently found to have left atrial SEC and left atrial thrombus by univariate analysis. Multivariate analysis showed that left atrial SEC (p < 0.001) was the only independent predictor of history of systemic embolism. Age, sex, left atrial or left ventricular dimension, left ventricular ejection fraction, antiplatelet or anticoagulant therapy and the percentage of lone atrial fibrillation were not significantly different between patients with and without left atrial SEC. Among the hematologic parameters, higher hematocrit was found in patients with left atrial SEC, while white blood cell and platelet counts were comparable in both groups. Platelet aggregability with different concentrations of inducers, adenosine diphosphate and collagen, was evaluated by the turbidimetric method in 15 patients with left atrial SEC and in 42 patients without left atrial SEC who were not receiving antiplatelet or anticoagulant therapy. No significant difference was found in platelet aggregability using four inducer concentrations between two groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Isolation and purification of glyceraldehyde-3-phosphate dehydrogenase from Schistosoma japonicum].

This paper recommends a simple and easy method to isolate and purify glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Schistosoma japonicum with electrophoretic purity. The recovery rate of 56.1% of glyceraldehyde-3-phosphate dehydrogenase from S. japonicum extract was achieved by ammonium sulfate precipitation, DEAE-cellulose column chromatography and SDS-PAGE. Using SDS-PAGE, the presence of one major band in the final purified GAPDH preparation was demonstrated. This protein had a MW of 37 kDa. The authors discuss the important functions of GAPDH and suggest that this method may be useful in the research of the protective immunity of S. japonicum GAPDH in the development of schistosome vaccine.

Animals↗
PubMed1994

Epstein-Barr virus-associated lymphoproliferative disorders in oral cavity after heart transplantation: report of a case.

Clinical manifestations of Epstein-Barr virus associated with post-heart transplant lymphoproliferative disorders (PTLD) are variable. Over one-half of the PTLD express extranodal presentations, of which gastrointestinal symptoms are the most common. Development of oral ulcers is an extremely rare initial manifestation with only three such cases having been reported. A case of oropharyngeal presentation of PTLD is described here. The clinical presentations and pathologic spectrums of PTLD are discussed. Posttransplant lymphoproliferative disorders are considered to be iatrogenic and life-threatening and are associated with immunosuppressive agents and Epstein-Barr virus infection. Early diagnosis and appropriate management could prevent the fatal progression of such disorders. The need to analyse tumor clonality along with observation of clinical presentations and microscopic pathology in order to diagnose PTLD is discussed.

Adolescent↗
PubMed1994

Effects of gemfibrozil on triglyceride metabolism in Dahl salt-sensitive rats.

Hypertriglyceridemia is a common feature of patients with increased blood pressure as well as several rodent models of hypertension. The goal of this study was to evaluate the effects of gemfibrozil on established abnormalities of triglyceride (TG) secretion and TG clearance in the Dahl salt-sensitive rat. Consequently, Dahl salt-sensitive rats received 12 days treatment with gemfibrozil (30 mg/kg/day) or vehicle by p.o. gavage and the following measurements were made: 1) fasting plasma TG levels; 2) TG secretion rate after suppression of TG removal with Triton WR 1339; 3) TG removal rate (half-time of disappearance of prelabeled very low density lipoprotein); and 4) lipoprotein lipase (LPL) activity and mRNA in soleus muscle, fat and liver tissues. Gemfibrozil produced a 50% reduction in fasting plasma TG concentrations, with no effect on TG secretion rate (17 +/- 2 vs. 15 +/- 1 mg/100 g b.wt./hr). The half-time of prelabeled very low density lipoprotein-TG removal was significantly lower in drug-treated animals (3.9 +/- 0.3 vs. 6.1 +/- 0.9 min), and this was associated with a tissue-specific increase in LPL activity in soleus muscle (153 +/- 5 vs. 135 +/- 5 U/g, P < .02). Expression of LPL mRNA, relative to beta-actin mRNA, was similar in both groups of rats. Thus, in this rodent model of hypertension and dyslipidemia, gemfibrozil lowers plasma TG levels by 50% with no effect on TG secretion; the hypotriglyceridemic effect is due mainly to an increase in TG removal rate associated with a post-transcriptional increase in LPL activity in skeletal muscle.

Adipose Tissue↗
PubMed1993

P59 (FK506 binding protein 59) interaction with heat shock proteins is highly conserved and may involve proteins other than steroid receptors.

P59 [also known as FK506 binding protein 59 (FKBP59) or heat shock protein 56 (hsp56)] and heat shock proteins 90 and 70 (hsp90 and hsp70) associate with steroid receptors and are believed to maintain the receptors in an inactive state. Recently, we showed that p59 purified from human lymphocytes is an immunophilin (FKBP59) which binds both FK506 and rapamycin. It was also demonstrated that immunosuppressant-FKBP59 complexes associate with hsp90, hsp70, and the glucocorticoid receptor [Tai, P.-K. K., Albers, M. W., Chang, H., Faber, L. E., & Schreiber, S. L. (1992) Science 256, 1315-1318]. Here we provide evidence that rabbit uterine p59 also binds FK506 and rapamycin and that p59 or its homologue is associated with nontransformed progesterone receptors of rabbit uterus and chicken oviduct. This suggests that the immunophilin-heat shock protein-steroid receptor interaction is ubiquitous and not limited to immune systems. A FKBP59 homologue complexed with hsp90-hsp70 was also detected in yeast, which suggests that the immunophilin-heat shock protein association has been evolutionarily conserved. In addition, we found that the FKBP59-hsp complexes are more complicated than previously thought, involving other proteins such as actin and a 63-kDa protein, p63. The association of p63 to the p59 complex was inhibited by FK506 and rapamycin, suggesting that p63 could be a potential target for the immunosuppressive actions of these two drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1993

Synthesis and anticonvulsant activity of enaminones. 2. Further structure-activity correlations.

This report continues the in-depth evaluation of methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxocyclohex-3-en-1-oate , 1 (ADD 196022), and methyl 4-(benzylamino)-6-methyl-2-oxocyclohex-3-en-1-oate, 2, two potent anticonvulsant enaminones. These compounds were evaluated employing the amygdala kindling model. Neither 1 nor 2 was active against amygdala kindled seizures, further supporting the corneal kindled model as a definitive tool for antielectroshock seizure evaluation as previously reported. Additional intraperitoneal (ip) data on 1 revealed toxicity at 24 h at 100 mg/kg. Several active analogs have been prepared with the view to minimizing toxicity. In a special ip rat screen developed by the Antiepileptic Drug Development (ADD) Program, these newer analogs were evaluated for protection against maximal electroshock seizures (MES) at 10 mg/kg and neurotoxicity at 100 mg/kg. From this screen, several compounds were shown to be safer alternatives, the most notable was methyl 4-[(p-bromophenyl)amino]-6-methyl-2-oxocyclohex-3-en-1-oate, 13. Compound 13 had an ip ED50 of 4 mg/kg in the rat and a TD50 of 269 mg/kg, providing a protective index (TD50/ED50) of > 67. By variation in the ring size, additional aromatic substitutions and the synthesis of acyclic analogs, these newer compounds provide a more definitive insight into the structure-activity correlation. CLOGP evaluation and molecular modeling studies are also provided to further elaborate the molecular characteristics of potential anticonvulsant enaminones.

Animals↗
PubMed1993

Identification of ras targets using a genetic approach.

The Sevenless receptor tyrosine kinase is required for the development of the R7 photoreceptor cell in the Drosophila eye. Several components of the Sevenless signal transduction pathway have been identified in genetic screens for enhancers/suppressors of the sevenless phenotype. These studies suggest that activation of Sevenless leads to stimulation of Ras1 activity, whereas Gap1 appears to act as a negative regulator of the pathway. Inactivation of the Gap1 locus causes transformation of non-neuronal cone cells into supernumerary R7 cells. This same mutant phenotype is observed when activated Ras1 is expressed under the control of the sevenless promoter. While studies in other organisms have demonstrated a role for ras gene products in signal transduction, the effectors of Ras activity have not yet been identified. We are carrying out genetic screens for enhancers and suppressors of the Gap1 and activated Ras1 phenotypes in the hope of identifying genes encoding some of these effectors. We are conducting chemical mutagenesis screens and have also screened existing collections of P element lines. A molecular characterization of the most promising mutations is in progress.

Animals↗
PubMed1993

Plasma endothelin levels and surgically correctable pulmonary hypertension.

To know the changes in plasma endothelin of patients with pulmonary hypertension, we studied 32 patients with valvular heart disease. Among them, 22 patients had pulmonary hypertension (group I) and 10 had pulmonary arterial pressures in the normal range (group II). Plasma endothelin-1 concentrations of the patients in group I were significantly greater than those of the patients in group II (p < 0.05). No significant difference in plasma endothelin-3 concentrations existed between the two groups. Cardiac output and pulmonary capillary wedge pressure had a linear correlation with plasma endothelin-1 levels. There was also a significant correlation between plasma endothelin-1 levels and hemodynamic indicators of severity of pulmonary hypertension, such as mean pulmonary arterial pressure and pulmonary vascular resistance (p < 0.05). All patients in this study underwent surgical procedures for the correction of valvular lesions. All patients in group I showed a decrease in pulmonary arterial pressures, and their plasma endothelin-1 levels decreased from 3.84 +/- 0.20 pg/mL to 1.66 +/- 0.07 pg/mL (p < 0.05), whereas the plasma endothelin-3 levels had only slight variation from 0.64 +/- 0.11 pg/mL to 0.75 +/- 0.06 pg/mL (p > 0.05) between the preoperative and the postoperative stages. The results demonstrated that plasma endothelin-1 rather than endothelin-3 had a role in pulmonary hypertension. Several pieces of evidence pointed out that endothelin-1 functioned as a reactive mediator during vasoconstriction in the case of pulmonary hypertension rather than as a triggering factor of pulmonary hypertension.

Adolescent↗
PubMed1993

Trauma outcome improves following the advanced trauma life support program in a developing country.

Trauma outcome variables before and after the institution of the Advanced Trauma Life Support (ATLS) program were compared for the largest hospital in Trinidad and Tobago from July 1981 through December 1985 (pre-ATLS) and from January 1986 to June 1990 (post-ATLS). A total of 199 physicians were ATLS trained by June 1990. Outcome data were analyzed for all dead or severely injured patients (ISS > or = 16; n = 413 pre-ATLS and n = 400 post-ATLS). Trauma mortality decreased post-ATLS (134 of 400 vs. 279 of 413) throughout the hospital, including the ICU (13.6% post-ATLS ICU mortality vs. 55.2% pre-ATLS). The odds of dying from trauma increased with age (1.02 for each year), ISS score (1.24 for each ISS increment), and blunt injury, both pre-ATLS and post-ATLS. Post-ATLS mortality was associated with a higher ISS (31.6 vs. 28.8). Although there was a higher percentage of blunt injury pre-ATLS (84.0%) versus post-ATLS (68.3%), the mortality rates for both blunt and penetrating injuries were higher in the pre-ATLS group (19.7% pre-ATLS vs. 6.3% post-ATLS for penetrating and 76.6% pre-ATLS versus 46.2% post-ATLS for blunt). For each ISS category, mortality was greater in the pre-ATLS group (ISS > or = 24 pre-ATLS mortality 47.9% vs. 16.7% post-ATLS; ISS 25-40 pre-ATLS mortality 91.0% vs. 71.0% post-ATLS). The overall ratio of observed to expected mortality based on the MTOS data base was lower for the post-ATLS period (pre-ATLS ratio 3.16; post-ATLS ratio 1.94).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Plasma endothelin level changes during hemorrhagic shock.

The purpose of this study was to analyze changes in plasma endothelin-1 levels during hemorrhagic shock. Thirty-two mongrel dogs were divided into four equal groups with group I as the controls and groups II through IV as experimental groups. The dogs in the experimental groups underwent hemorrhagic procedures. The mean blood pressure was kept at the level of 65 mm Hg in group II, 50 mm Hg in group III, and 40 mm Hg in group IV. Blood samples were collected from each dog under the following conditions: (1) after induction of anesthesia, when the animals were hemodynamically stable, before the start of shock; (2) 1 minute after the mean arterial pressure dropped to the level designed for each group (shock 1); (3) 15 minutes after shock 1; (4) 30 minutes after shock 1; (5) 1 hour after shock 1; (6) 2 hours after shock 1; (7) 4 hours after shock 1; and (8) 8 hours after shock 1. Plasma endothelin-1 levels both in arterial and venous blood were analyzed in each dog. The results showed that (1) arterial endothelin-1 concentrations were considerably lower than venous concentrations at the baseline level; (2) after the shock-1 point, plasma endothelin-1 concentrations increased, first markedly and then evenly throughout the oligemic period; (3) elevation of plasma endothelin-1 levels was significantly linearly correlated with the amount of blood loss at the time of 2 hours after shock and thereafter; (4) the arterial/venous ratio of plasma endothelin-1 levels during the oligemic period was higher than that in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of pH on endothelin-1 secretion of aortic strips.

In this study, aortic strips taken from mongrel dogs were used as experimental material. After preparation, the aortic strips were incubated in a designed control medium or an experimental medium (adding thrombin or epinephrine to the control medium). The pH value of each incubation medium mentioned above was adjusted with HCl or NaOH to a level of 8.0, 7.4, 7.0 and 6.6, respectively, in order to investigate the influence of medium acidity on the production of endothelin-1 from endothelial cells using aortic strips. After a designated time duration (one hour, three hours, six hours and 12 hours, respectively), the incubation media were collected for assay of endothelin-1. The results demonstrated that the endothelin-1 level of the incubation medium was elevated when: 1) the incubation time was lengthened; 2) the incubation medium was more acidic; 3) the aortic strips were incubated with a stimulant, such as thrombin and epinephrine; and 4) the endothelial cells on the aortic strips were intact. This indicates that the secretion of endothelin-1 is: 1) time-dependent, 2) pH-dependent, 3) stimulant-dependent and 4) endothelium-dependent.

Animals↗
PubMed1993

[The effect of surface area of active recording electrode to CMAP parameters].

The purpose of this study is to quantitatively evaluate the effect of surface area of active recording electrodes to CMAP. The APB muscles from 19 young healthy subjects were included. The evoked CMAPs from median nerve supramaximal stimulation at wrist were recorded with regular surface disc electrode. Then the active recording electrode were changed to 1/2 surface area of disc, 1/4 surface area of disc, monopolar needle and concentric needle at the same recording sites. Computer reading of the latency, duration, amplitude and surface area of the CMAP were done and compared to that of standard electrode. Results disclosed that decrease the surface area of active recording did not significantly influence the distal latency, duration, amplitude and surface area of the CMAP (p > 0.1), although tendency to increase the amplitude and area were noted. The recording abilities of the active recording and the surface area difference between active recording and reference were considered to be the contributing factors. In clinical application such as recording an area with skin defect, the surface area of active recordling electrode can be altered without significant distortion of CMAP parameters.

Action Potentials↗