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Biomedical subjects

H C Chang

Publications and source records attributed to H C Chang.

At least 109 records · Page 6Linked to original sources

The effect of biological dyes and contrast media on the vas deferens in Long Evans rats.

The conventional diagnostic procedure of vasography utilizes a contrast medium to evaluate the patency of the vas deferens. With the development of microsurgical reconstruction for obstructive azoospermia in the past two decades, intraoperative vasography with saline or biological dye injection has replaced the use of radiographic contrast media. However, there are few reports on the effect of biological dyes on the healthy vas deferens. Therefore, we used experimental vasography to evaluate histological changes and functional patency of the vas deferens after infusion with a contrast medium and biological dye. Four groups of 10 Long Evans male rats were injected by vasopuncture with 1% methylene blue, 1% gentian violet and 38% Urografin or saline into the vas deferens. The animals were killed 30 days later, and the vasa deferentia were excised and examined for histological changes and for functional patency. Vasopuncture with saline injection induced minimal change both at the puncture site and in the distal vas deferens. In both the Urografin- and methylene blue-injected groups, inflammation at the puncture site was found in 20-22% of cases, and 10-11% of cases revealed functional obstruction of the vasal lumen. In the gentian violet-injected group, severe histological and obliterated changes were found in all cases. Leakage of the dye and contrast medium or the sperm reaction may be responsible for the inflammation; otherwise, methylene blue and urografin did not seem to be harmful to the vas deferens. Although gentian violet is a blue dye, as is methylene blue, it has marked destructive effects on the vas deferens. It is concluded that some biological dyes used for vasal injection can cause occlusion of the vasal lumen, while inflammatory responses can occur from placing a needle transmurally.

Animals↗

In vivo evaluation of serotonergic agents and alpha-adrenergic blockers on premature ejaculation by inhibiting the seminal vesicle pressure response to electrical nerve stimulation.

OBJECTIVE: To evaluate the effect of drugs on premature ejaculation using a rat animal model in which the seminal vesicle was electrically stimulated via its lesser splanchnic nerve and changes in the pressure response monitored. MATERIALS AND METHODS: Male Wistar rats (aged 12-14 weeks) were injected intravenously with prazosin and serotonergic agents (serotonin, clomipramine, fluoxetine, imipramine and indatraline) at various concentrations 10 min before electrical nerve stimulation (ENS) of the lesser splanchnic nerve; the initial increase in seminal vesicle pressure in response to ENS was then compared. RESULTS: The pressure response to ENS was reduced in the presence of prazosin or serotonergic agents. The mean (SEM) maximum inhibition values were 84.1 (8.9%) by fluoxetine at 0.1 mg/kg, 67.9 (8.7)% by prazosin at 0.1 mg/kg, 60.9 (11.0)% by serotonin at 3 mg/kg, 54.9 (4.6)% by clomipramine at 3 mg/kg, 30.0 (11.0)% by imipramine at 0.1 mg/kg, and 20.9 (4.3)% by indatraline at 0.1 mg/kg. From the concentration-response curve, the potency of prazosin was lower than that of fluoxetine, but was higher than that of serotonin or clomipramine. CONCLUSIONS: Like serotonin, fluoxetine and clomipramine can reduce the pressure response of the seminal vesicle to ENS. Among these inhibitory agents, including prazosin, fluoxetine was the most effective and may be valuable for the clinical treatment of ejaculatory dysfunction in man.

Adrenergic Uptake Inhibitors↗

Adding ketamine in a multimodal patient-controlled epidural regimen reduces postoperative pain and analgesic consumption.

UNLABELLED: We designed this double-blind study to evaluate the effect of adding small-dose ketamine in a multimodal regimen of postoperative patient-controlled epidural analgesia (PCEA). Ninety-one patients, ASA physical status I-III, undergoing major surgery, received a standardized general anesthesia and epidural catheterization in an appropriate intervertebral space after surgery. A PCEA device was programmed to deliver a regimen of morphine 0.02 mg/mL, bupivacaine 0.8 mg/mL, and epinephrine 4 microg/mL, with the addition of ketamine 0.4 mg/mL (ketamine, n = 45) or without (control, n = 46). The mean visual analog pain scale (VAS) scores during cough or movement for the first 3 days after surgery were higher in the control group than in the ketamine group (P < 0.05), whereas the mean VAS score at rest for the first 2 days were higher in the control group than in the ketamine group (P < 0.05). Furthermore, patients in the control group consumed more multimodal analgesics than patients in the ketamine group for the first 2 days (P < 0.05). The sedation scores and the incidence of side effects (pruritus, nausea, emesis, sleep deprivation, motor block, and respiration depression) were similar between the two groups. We conclude that adding ketamine 0.4 mg/mL in a multimodal PCEA regimen provides better postoperative pain relief and decreases consumption of analgesics. IMPLICATIONS: Many studies have evaluated one or a combination of two analgesics for postoperative pain control, but few have examined a multimodal approach using three or four different epidural analgesics. This study demonstrates an additive analgesic effect when ketamine is added to a multimodal analgesic treatment.

Analgesia, Epidural↗

Sialadenoma papilliferum of the esophagus.

Sialadenoma papilliferum is an extremely rare benign tumor of the esophagus. We report a 70-yr-old woman who was first thought to have adenocarcinoma in the distal esophagus. Transhiatal esophagectomy and left colon interposition were performed. The pathological diagnosis of sialadenoma papilliferum of the esophagus arising in the submucosal gland ducts was confirmed after surgery.

Adenocarcinoma↗

Effects of Chinese herbal prescriptions on copulatory activity in aged male rats: a preliminary study.

Four herbal prescription medicines, Chi-Pao-Mei-Jan-Tan, Gui-Fu-Ba-Wei-Wan, Huan-Shao-Tan; and San Tsai-Feng-Sui-Tan, were tested for their effects on sexual behavior in aged rats. Crude liquid extracts of these herbs were administered to the rats daily through oral tubing for 14 days. All four herbal prescriptions showed some effects in restoration of mount and intromission behaviors, but there was no effect on restoration of ejaculation in 26 month old rats that had exhibited no copulatory activity (no mount, intromission and ejaculation) previously. The effects of Chi-Pao-Mei-Jan-Tan were further tested in 26 month old rats with low mount and intromission activities but without ejaculation behavior, and in 15 month old rats (middle-age group) that showed normal mount and intromission behavior but no ejaculation activity. Chi-Pao-Mei-Jan-Tan was effective in improving the frequency of both mount and intromission, but failed to restore the ejaculation activity of the old rats with low mount and intromission behaviors. It was, however, very effective in restoration of ejaculation activity in middle-aged rats that exhibited normal mount and intromission behaviors. Serum testosterone (T) levels of Chi-Pao-Mei-Jan-Tan in tested old and middle-aged rats were determined by radioimmunoassay, and showed no difference before and after treatment. Our findings demonstrated that the four herbal prescriptions had some effects in restoration of mount and intromission behaviors, but not ejaculation activity in old rats, and that Chi-Pao-Mei-Jan-Tan was very effective in restoration of ejaculation activity in middle-aged rats. The promotional effect of Chi-Pao-Mei-Jan-Tan on copulatory behavior was not correlated with serum T levels.

Aging↗

Pregnane glycosides, gymnepregosides A-F from the roots of Gymnema alternifolium.

The structural elucidation of six new related polyoxypregnane glycosides, gymnepregosides A (1), B (2), C (3), D (4), E (5) and F (6), together with two known compounds, from the roots of Gymnema alternifolium (Asclepiadaceae) was achieved through on a detailed study of 1H- and 13C-NMR spectral data and chemical means. The results obtained for new compounds, 1-6, show that they are (20S)-pregn-6-ene-3 beta,5 alpha,8 beta,12 beta,14 beta,17 beta,20-heptaol or sarcostin 3-O-glycosides, and all the sugars at C-3 are beta(1-->4)-linked. Some of them possessed benzoyl, cinnamoyl and tigloyl residues as the ester linkages located at C-12 and/or C-20 of the aglycon.

Carbohydrate Sequence↗

Determination of acceptability of flavored oat bran frankfurters by older adults.

The US population is aging rapidly and, within the next 25 years, 20-25% will be over age 60. This creates a vast new market for age-specific products and increases the responsibility of food scientists and nutritionists to provide appropriate foods for older adults. Many older individuals are energy deficient and need to be encouraged to consume more food in order to maintain body weight and health, but need to decrease the calories from fat in their diets. Many of these older individuals are not inclined to eat foods that they enjoy for fear that these foods may be detrimental to their health (de Castro, 1993), or they have lost their gustational abilities to the degree that these foods are no longer enjoyable. This research looks at a possible solution to both problems by replacing fat in a favorite food of older adults and adjusting the flavor levels of this product. Frankfurters were made from mechanically deboned poultry meat in which standard commercial formulation was compared to three flavoring treatments using oat bran as a fat replacer (6% oat bran, 30% H2O). Mixed spices (traditional saucisson) were added to two of these treatments in standard and double proportions. Participants were 71 individuals over the age of 65 in varying levels of health from four regional care facilities. Seven gram, three-digit-coded samples were evaluated at 60 degrees C, and scored on a nine-point hedonic scale. A significant (alpha = 0.0004) preference was shown for the double-spiced frank. No differences by sex or race were found. Research concluded that addition of flavoring aids in the increased acceptability of products by older adults.

Aged↗

Haematuria clinic--a preliminary audit and considerations for a one-stop assessment centre.

AIM: To audit and study the practicality of an integrated Haematuria Clinic as a one-stop assessment centre for the investigations of patients presenting with haematuria. METHODS: A weekly clinic was organised to facilitate consultation, intravenous urogram and flexible cystoscopy for patients with haematuria. A protocol was set up and data on symptoms, types of haematuria, results of the investigations and outcomes were collected. RESULTS: About half of all the patients seen in this clinic were found to harbour urological lesions; of which urolithiasis (20.4%) and urological malignancies (14.2%) were the most common lesions identified. Transitional cell carcinoma of the bladder was the most common malignancy diagnosed (8%). Significantly, 2 of 9 (22.2%) bladder cancers were found on cystoscopy and missed on the cystogram phase of the intravenous urogram. Ten urological lesions would have been missed if cystoscopies were not performed. Conversely, in 14 patients, cystoscopy could be avoided because their intravenous urograms identified lesions sufficiently to allow for definitive treatment. CONCLUSIONS: The need and types of investigation for patients with haematuria are evolving. We recommend intravenous urogram and flexible cystoscopy as the standard investigations and caution against ignoring microscopic haematuria. These assessments can be organised into an integrated clinic improving deliverance of clinical care; which may result in better patient compliance for investigations and earlier detection and treatment of urological lesions presenting as haematuria.

Adult↗

Comparison of hemodynamics and recovery of sevoflurane and isoflurane anesthesia in Chinese adult patients.

BACKGROUND: The new inhalational anesthetic sevoflurane would be expected to provide a rapid emergence from anesthesia due to its low blood/gas partition coefficient. In this study, we compared the hemodynamic effects, speed and quality of emergence, in ASA class I-II Chinese adult surgical patients receiving either sevoflurane or isoflurane anesthesia. METHODS: Eighty adult Chinese patients, ASA class I-II, scheduled for elective gynecological or general surgical procedures, were randomized to receive sevoflurane (n = 40) or isoflurane (n = 40) anesthesia. Ventilation is controlled via endotracheal intubation with anesthesia facilitated by either agent at anesthetic concentration of 1-1.5 MAC under the fresh gas flow 2 L/min. Heart rate, arterial blood pressure, temperature, SpO2 and end-tidal CO2 were continuously monitored. Any adverse effect such as airway irritation, nausea or vomiting was recorded during induction and emergence from anesthesia. The emergence time was assessed by various questionales for orientation during recovery. In the post-anesthetic recovery period, pain was monitored and managed by objective pain discomfort scale for analgesic supplements. Complaints of nausea and vomiting were recorded and followed up by a research nurse who visited the patient within 24 h following surgery. RESULTS: The extent of exposure to anesthetic (MAC x hours) was similar in both groups. Sevoflurane and isoflurane caused similar alterations in systolic and diastolic arterial pressure during maintenance. After surgical incision, the heart rate accelerated more in patients receiving isoflurane (p < 0.05). During emergence, time of response to command was significantly shorter in patients receiving sevoflurane than patients receiving isoflurane (5.6 +/- 0.4 min versus 15.2 +/- 3.0 min, p < 0.001). Side effects such as nausea and vomiting were comparable in both groups. CONCLUSIONS: Compared with isoflurane, sevoflurane anesthesia had the clinical advantages of maintaining stable hemodynamics and rapid recovery in Chinese adult patients.

Adult↗

Topology of NAT2, a prototypical example of a new family of amino acid transporters.

Amino acids are the predominant form of nitrogen available to the heterotrophic tissues of plants. These essential organic nutrients are transported across the plasma membrane of plant cells by proton-amino acid symporters. Our lab has cloned an amino acid transporter from Arabidopsis, NAT2/AAP1, that represents the first example of a new class of membrane transporters. We are investigating the structure and function of this porter because it is a member of a large gene family in plants and because its wide expression pattern suggests it plays a central role in resource allocation. In the results reported here, we investigated the topology of NAT2 by engineering a c-myc epitope on either the N or C terminus of the protein. We then used in vitro translation, partial digestion with proteinase K, and immunoprecipitation to identify a group of oriented peptide fragments. We modeled the topology of NAT2 based on the lengths of the peptide fragments that allowed us to estimate the location of protease accessible cleavage sites. We independently identified the location of the N and C termini using immunofluorescence microscopy of NAT2 expressed in COS-1 cells. We also investigated the glycosylation status of several sites of potential N-linked glycosylation. Based on the combined data, we propose a novel 11 transmembrane domain model with the N terminus in the cytoplasm and C terminus facing outside the cell. This model of protein topology anchors our complementary investigations of porter structure and function using site-directed and random mutagenesis.

Amino Acid Transport Systems↗

Anti-thyroid isoflavones from soybean: isolation, characterization, and mechanisms of action.

The soybean has been implicated in diet-induced goiter by many studies. The extensive consumption of soy products in infant formulas and in vegetarian diets makes it essential to define the goitrogenic potential. In this report, it was observed that an acidic methanolic extract of soybeans contains compounds that inhibit thyroid peroxidase- (TPO) catalyzed reactions essential to thyroid hormone synthesis. Analysis of the soybean extract using HPLC, UV-VIS spectrophotometry, and LC-MS led to identification of the isoflavones genistein and daidzein as major components by direct comparison with authentic standard reference isoflavones. HPLC fractionation and enzymatic assay of the soybean extract showed that the components responsible for inhibition of TPO-catalyzed reactions coeluted with daidzein and genistein. In the presence of iodide ion, genistein and daidzein blocked TPO-catalyzed tyrosine iodination by acting as alternate substrates, yielding mono-, di-, and triiodoisoflavones. Genistein also inhibited thyroxine synthesis using iodinated casein or human goiter thyroglobulin as substrates for the coupling reaction. Incubation of either isoflavone with TPO in the presence of H2O2 caused irreversible inactivation of the enzyme; however, the presence of iodide ion in the incubations completely abolished the inactivation. The IC50 values for inhibition of TPO-catalyzed reactions by genistein and daidzein were ca. 1-10 microM, concentrations that approach the total isoflavone levels (ca. 1 microM) previously measured in plasma from humans consuming soy products. Because inhibition of thyroid hormone synthesis can induce goiter and thyroid neoplasia in rodents, delineation of anti-thyroid mechanisms for soy isoflavones may be important for extrapolating goitrogenic hazards identified in chronic rodent bioassays to humans consuming soy products.

Antithyroid Agents↗

Topology of T cell receptor-peptide/class I MHC interaction defined by charge reversal complementation and functional analysis.

The molecular interactions between the CD8 co-receptor dependent N15 and N26 T cell receptors (TCRs) and their common ligand, the vesicular stomatitis virus octapeptide (VSV8) bound to H-2Kb, were studied to define the docking orientation(s) of MHC class I restricted TCRs during immune recognition. Guided by the molecular surfaces of the crystallographically defined peptide/MHC and modeled TCRs, a series of mutations in exposed residues likely contacting the TCR ligand were analyzed for their ability to alter peptide-triggered IL-2 production in T cell transfectants. Critical residues which diminished antigen recognition by 1000 to 10,000-fold in molar terms were identified in both N15 Valpha (alphaE94A or alphaE94R, Y98A and K99) and Vbeta (betaR96A, betaW97A and betaD99A) CDR3 loops. Mutational analysis indicated that the Rp1 residue of VSV8 is critical for antigen recognition of N15 TCR, but R62 of H-2Kb is less critical. More importantly, the alphaE94R mutant could be fully complemented by a reciprocal charge reversal at Kb R62 (R62E). This result suggests a direct interaction between N15 TCR Valpha E94R and Kb R62E residues. As Rp1 of VSV8 is adjacent to R62 in the VSV8/Kb complex and essential for T cell activation, this orientation implies that the N15 Valpha CDR3 loop interacts with the N-terminal residues of VSV8 with the Valpha domain docking to the Kb alpha2 helix while the N15 Vbeta CDR3 loop interacts with the more C-terminal peptide residues and the Vbeta domain overlies the Kb alpha1 helix. An equivalent orientation is suggested for N26, a second VSV8/Kb specific TCR. Given that genetic analysis of two different class II MHC-restricted TCRs and two crystallographic studies of class I restricted TCRs offers a similar overall orientation of V domains relative to alpha-helices, these data raise the possibility of a common docking mode between TCRs and their ligands regardless of MHC restriction.

Amino Acid Sequence↗

Heat stress induces tyrosine phosphorylation/activation of kinase FA/GSK-3 alpha (a human carcinoma dedifferentiation modulator) in A431 cells.

Exposure of A431 cells to a rapid temperature increase from 37 degrees to 46 degrees C could induce an increased expression (approximately 200% of control) and tyrosine phosphorylation/activation (approximately 300% of control) of protein kinase FA/ glycogen synthase kinase-3 alpha (kinase FA/GSK-3 alpha) in a time-dependent manner, as demonstrated by an anti-kinase FA/GSK-3 alpha immunoprecipitate kinase assay and by immunoblotting analysis with anti-kinase FA/GSK-3 alpha and anti-phosphotyrosine antibodies. The heat induction on the increased expression of kinase FA/GSK-3 alpha could be blocked by actinomycin D but not by genistein. In contrast, the heat induction on tyrosine phosphorylation/activation of kinase FA/GSK-3 alpha could be blocked by genistein or protein tyrosine phosphatase, indicating that heat stress induces a dual control mechanism, namely, protein expression and subsequent tyrosine phosphorylation to cause cellular activation of kinase FA/GSK-3 alpha. Taken together, the results provide initial evidence that kinase FA/GSK-3 alpha represents a newly described heat stress-inducible protein subjected to tyrosine phosphorylation/activation, representing a new mode of signal transduction for the regulation of this human carcinoma dedifferentiation modulator and a new mode of heat induction on cascade activation of a protein kinase.

Calcium-Calmodulin-Dependent Protein Kinases↗

14-3-3 epsilon positively regulates Ras-mediated signaling in Drosophila.

We have isolated mutations in the gene encoding a Drosophila 14-3-3 epsilon protein as suppressors of the rough eye phenotype caused by the ectopic expression of RAS1(V12). Using a simple loss-of-function 14-3-3 epsilon mutation, we show that 14-3-3 epsilon acts to increase the efficiency of RAS1 signaling. The 14-3-3 epsilon protein appears to function in multiple RTK pathways, suggesting that it is a general component of RAS1 signaling cascade. Sequence analysis of three dominant-negative alleles defines two regions of 14-3-3 epsilon that participate in RAS1 signaling. We also present evidence that 14-3-3 epsilon and 14-3-3 zeta, two 14-3-3 protein family members, are partially redundant for RAS1 signaling in photoreceptor formation and in animal viability. Our genetic data suggest that 14-3-3 epsilon functions downstream of or parallel to RAF, but upstream of nuclear factors in RAS1 signaling.

14-3-3 Proteins↗

Major histocompatibility complex recognition by immune receptors: differences among T cell receptor versus antibody interactions with the VSV8/H-2Kb complex.

The surface residues of the VSV8/Kb complex important for recognition by N15 and N26 alphabeta T cell receptors (TCR) were mapped by mutational analysis and compared to each other and with epitopes of well-characterized Kb specific monoclonal antibodies (mAb). Three features of immune receptor recognition emerge. First, the footprints of the two TCR on VSV8/Kb are similar with more than 80 % overlap between sites. Given that only 8 of 14 surface exposed VSV8/Kb residues identified as critical for TCR interaction are in common, the chemical basis of the N15 and N26 interactions is nevertheless distinct. Second, the cognate peptide is a major focus of TCR recognition: mutation at any of the three exposed side chains (at p1, p4 or p6) abrogates interaction of both TCR as measured by functional T cell activation. Third, in contrast to TCR, mAb bind to discrete segments on the periphery of the alpha1 and/or alpha2 helices without orientational restriction. These findings suggest that unlike soluble antibodies, surface membrane receptor-ligand interactions on opposing cells (i.e. TCR-peptide/ MHC, CD8-MHC) limit the orientational freedom of the TCR in the immune recognition process.

Animals↗

Double-positive T cell receptor(high) thymocytes are resistant to peptide/major histocompatibility complex ligand-induced negative selection.

To investigate negative selection events during intrathymic ontogeny, we established T cell receptor (TCR)-transgenic mice [N15tg/RAG-2-/- (H-2b)] expressing a single TCR specific for vesicular stomatitis virus nuclear octapeptide N52-59 (VSV8) in the context of the major histocompatibility complex (MHC) class I molecule, K(b). Administration of VSV8 in vivo induced apoptosis in less than 4 h, deleting the majority of immature double-positive (DP) thymocytes by 24 h. In contrast, DP TCRhigh as well as single-positive (SP) thymocytes were refractory to this death process. Moreover, DP TCRhigh cells differentiated into SP thymocytes in vitro and in vivo, maturing into functional cytotoxic T lymphocytes upon intrathymic transfer to beta RAG 2-/- recipients. Hence, negative selection processes involving MHC-bound peptide ligands are operative only prior to the late DP thymocyte stage in this MHC class I-restricted TCR transgene system.

Animals↗