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Biomedical subjects

C C Chang

Publications and source records attributed to C C Chang.

At least 397 records · Page 22Linked to original sources

Clinical experience of octreotide in the treatment of acromegaly.

To evaluate the efficacy and safety of octreotide (a somatostatin analogue) in the treatment of acromegaly, 10 patients were injected subcutaneously with octreotide, 50 micrograms, thrice daily before each meal for two days, followed by 100 micrograms thrice daily for six months. One case dropped out at the initial stage because of diarrhea, and another quit due to a lack of improvement in headaches after treatment for three months. Eight patients completed the study. The results showed that the circumference of the fourth finger and hand volume significantly decreased after treatment. Laboratory data demonstrated that serum growth hormone (GH) and somatomedin-C levels also decreased significantly. However, in six patients without a history of trans-sphenoidal adenomectomy, the serum GH and somatomedin-C levels returned to normal in only one case who had a serum GH level < 20 mU/L before treatment. In the oral glucose tolerance test, paradoxic elevation of GH subsided after treatment. In the TRH test, paradoxic elevation of GH improved after treatment. In the bromocriptine test, octreotide had a synergistic effect on the suppression of GH. All cases had the side effect of injection pain, especially at the initial stage. An increase in intestinal peristalsis and bowel movement occurred in the first week, but symptoms later subsided. Two out of these eight patients had gallbladder sludge after six months of treatment. In conclusion, octreotide is effective in the treatment of acromegaly; however, it is better used in patients who have serum GH levels < 20 mU/L, or after a trans-sphenoidal adenomectomy, and may be combined with bromocriptine to treat the patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

Histiocytosis X with thyroid involvement: report of a case.

Histiocytosis X is a disease of histiocyte proliferation in response to some unknown etiology. Thyroid involvement is extremely rare in the literature. In this paper, we present an 18-year-old female with histiocytosis X with thyroid involvement. This patient had had a goiter with normal thyroid function since 12 years of age. A thyroidectomy was done under the suspicion of thyroid cancer. Pathology revealed histiocytosis X. Hypoparathyroidism and hypothyroidism were noted after the operation and were treated with thyroid hormone, vitamin D and calcium carbonate. This patient also had lesions on the left side of mandible, in the suprasellar region and possibly in the right mastoid. A curettage biopsy of her mandibular lesion was also compatible with histiocytosis X. She was proven to have hypothalamic and pituitary dysfunction including hypogonadism and hypoadrenalism. Her thyroid lesion did not recur after the thyroidectomy. The toothache that she had also experienced subsided after the curettage biopsy of the mandibular lesion. Hypothalamic and pituitary dysfunction were controlled by hormone replacement. Because her disease had been running a benign clinical course, no chemotherapy was given.

Adolescent↗

Roles of the aromatic residues in cobrotoxin in antigenicity and binding activity to nicotinic acetylcholine receptor.

The single Trp-29 in cobrotoxin was modified with 2-hydroxy-5-nitrobenzyl bromide, and Tyr-25 and -35, with tetranitromethane. Although the binding activity of cobrotoxin to the nicotinic acetylcholine receptor (nAChR) was decreased after modification of Trp-29, the antigenicity remained essentially unchanged as measured by a competitive RIA. Tyr-35-nitrated cobrotoxin still retained relatively high antigenicity and potent binding activity to nAChR. However, modification of both Tyr-25 and Tyr-35 led to an altered secondary structure, with greatly reduced binding to antibody and receptor. Hence, Tyr-25 in cobrotoxin is essential for the maintenance of the active conformation for the bindings. Although the non-precipitating antibody against cobrotoxin exhibiting a higher neutralizing capacity than did the precipitating antibody, the binding affinity of the former to cobrotoxin and its modified derivatives was lower than that of the latter.

Animals↗

[Preparation and characterization of antibodies against Bungarus multicinctus venom by liposomes].

Bungarus multicinctus venom was incorporated into sphingomyelin-cholesterol liposomes which were stabilized with osmium tetroxide. The lethal toxicity of B. multicinctus venom in osmicated liposomes greatly decreased to 1.03% that of crude venom. Rabbits were divided into four groups for immunization. Group A was immunized with crude venom, group B and group C with osmicated liposomes, and group D with osmicated liposomes followed by the crude venom. Immunization was performed in the presence of Freund's adjuvant except for group B. The antibody levels during the course of immunization were measured by ELISA and the contents of precipitating antibody were determined by quantitative precipitin reactions, while that of non-precipitating antibody was determined by affinity chromatography. Although the immune response was not increased by incorporating lipopolysaccharide immunostimulant, the specific neutralizing capacity of purified antibody from the pooled antisera of group D was more potent than that of the others. The almost non-toxic osmicated liposomes of B. multicinctus venom may be useful immunogens for the production of antiserum for treatment of snake bites.

Animals↗

Chemical modification of alpha-bungarotoxin with bifunctional reagent, 1,5-difluoro-2,4-dinitrobenzene.

alpha-Bungarotoxin (alpha-BuTX) was modified with a bifunctional reagent, 1,5-difluoro-2,4-dinitrobenzene (DFDNB) to prepare the cross-linked derivatives. The modified products, obtained from the reaction at pH 8.5 with a 2-fold molar excess of DFDNB, were purified successively on a Sephadex G-50 and a SP-Sephadex C-25 columns, and, fast protein liquid chromatography (FPLC) on a Mono S column. The preparation was proved to be a homogeneous and dimeric form which arose from the intermolecular cross-linkage of alpha-BuTX through a dinitrophenylene (DPE) group. The cross-linked alpha-BuTX derivative still retained approximately 50% residual lethality and 70% residual binding activity to nicotinic acetylcholine receptor (nAChR). The modified derivative also showed relatively high antigenic activity toward anti-alpha-BuTX antibody as measured by competitive radioimmunoassay (RIA).

Animals↗

B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50.

A B cell lymphoma-associated chromosomal translocation, t(10;14)(q24;q32), juxtaposes the immunoglobulin C alpha 1 locus to a novel gene, lyt-10. The normal lyt-10 cDNA codes for a 98 kd protein which displays amino-terminal homology with the rel (DNA-binding) domain of the NF-kappa B-rel family of transcription factors and carboxy-terminal homology with the NF-kappa B p50 precursor protein, including the putative proteolytic cleavage domain (poly-G) and the ankyrin-like repeat domains. The lyt-10 protein can bind to kappa B sequences in vitro, although with different specificity from NF-kappa B p50, and in vitro DNA-binding is activated by removal of the ankyrin domain. Chromosomal translocation generates an lyt-10-C alpha 1 fusion gene coding for a protein that retains the rel effector domain, lacks the ankyrin regulatory domain, and binds kappa B sequences in vitro, suggesting its constitutive activation in vivo. Analogous rearrangements of the lyt-10 gene have been found in an additional three cases of lymphoid neoplasia. The lyt-10 gene defines a new subfamily (rel/poly-G/ankyrin) of NF-kappa B-rel transcription factors with potential for oncogenic activation in human cancer.

Amino Acid Sequence↗

Modulation of antiviral activity of interferon and 2',5'-oligoadenylate synthetase gene expression by mild hyperthermia (39.5 degrees C) in cultured human cells.

The antiviral/antiproliferative/antitumor properties of interferon (IFN) are potentiated by a febrile temperature (Heron, I., and Berg, K. (1978) Nature 274, 508-510; Fleischmann, W. R., Fleischmann, C. M., Jr., and Gindhart, T. D. (1986) Cancer Res. 46, 1722-1726; Groveman, D. S., Borden, E. C., Merritt, J. A., Robins, H. I., Steeves, R., and Bryan, G. T. (1984) Cancer Res. 44, 5517-5521). To investigate the role of 2',5'-oligoadenylate (2-5A) synthetase in linking temperature with these biological functions of IFN, antiviral activities and expression of the 2-5A synthetase gene were measured simultaneously in control and type I IFN-treated HL-60 and WISH cells at the selected elevated temperature of 39.5 degrees C +/- 0.5 degrees C (herein referred to as hyperthermia). In both cell lines, the IFN-mediated antiviral effect was enhanced 3-10-fold. Concurrently, enzymatic assays and immunoblot analyses with an anti-40-kDa synthetase antibody clearly gave a 2-3-fold increase of synthetase above that observed at the normal cell culture temperature (37 degrees C). These results suggest that potentiation of 2-5A synthetase must partially account for the enhanced antiviral activity of IFN at the higher cell culture temperature. The supranormal elevation of 2-5A synthetase was accompanied by a parallel increase in the steady-state concentration of 2-5A synthetase mRNA, which is likely to contribute to the observed increase in enzyme level. Transient reporter gene expression studies using plasmid constructs carrying 2-5A synthetase gene promoter linked in tandem with chloramphenicol acetyltransferase showed that IFN-inducible chloramphenicol acetyltransferase activity was not influenced by hyperthermia, suggesting that transcription activation is an unlikely explanation for the observed 2-5A synthetase mRNA level increases. Messenger RNA stability assays showed that the half-life (t1/2) of 2-5A synthetase mRNA was extended from 2 to 4 h at 39.5 degrees C. Under identical conditions, the t1/2 of poly(A)+ RNA remained unchanged whereas the t1/2 of beta-actin mRNA was reduced. Taken together, these results are consistent with the interpretation that selective stabilization of 2-5A synthetase mRNA at the elevated temperature is a major factor contributing to the potentiation of antiviral activity of IFN by hyperthermia.

2',5'-Oligoadenylate Synthetase↗

Effect of Staphylococcus epidermidis on adherence of Pseudomonas aeruginosa and Proteus mirabilis to polymethyl methacrylate (PMMA) and gentamicin-containing PMMA.

The goals of this study were to determine 1) effect of Staphylococcus epidermidis adherence and biofilm production on adherence of the opportunistic pathogens Proteus mirabilis and Pseudomonas aeruginosa to polymethyl methacrylate (PMMA); 2) if the biofilm killed by autoclaving altered adherence of other organisms; 3) if adherence of S. epidermidis to gentamicin-containing PMMA altered adherence of the opportunistic pathogens P. mirabilis and P. aeruginosa to gentamicin-containing PMMA. Results show that biofilms formed by S. epidermidis, whether alive or dead, significantly increased adherence of Pseudomonas. Adherence of Proteus was significantly increased on dead biofilms and increased, but not significantly (p = less than 0.1), on live ones. Greatest adherence seen in the study was to autoclaved biofilms. Significant adherence of Proteus and Pseudomonas was found on gentamicin-containing PMMA specimens, which were preincubated with S. epidermidis for formation on the biofilm. These results indicate that a biofilm is formed on PMMA-gentamicin specimens and this may impair the ability of gentamicin to kill other organisms.

Bacterial Adhesion↗

Studies on the status of amino groups in alpha-bungarotoxin.

The positive charges of amino groups in alpha-bungarotoxin (alpha-BuTX) were neutralized by reaction with trinitrobenzene sulfonate (TNBS) and were converted into negative charges with 4-chloro-3,5-dinitrobenzoate (CDNB). Three derivatives monotrinitrophenylated (TNP-) at Lys-38, 64, or 70; three di-TNP at Lys-38 and 64, Lys-38 and 70, and Lys-64 and 70; one tri-TNP at Lys-38, 64 and 70; and one penta-TNP at Lys-38, 51, 52, 64 and 70 as well as one mono-carboxydinitrophenylated (CDNP-) at Lys-38; di-CDNP at Lys-38 and 70, and tri-CDNP at Lys-38, 64 and 70 were isolated, respectively. The epsilon-amino groups at Lys-38, 64 and 70 are the most accessible to trinitrophenylation, Lys-51 and 52 are less reactive, while the N-terminus and Lys-26 are the least reactive. Each mono-TNP and CDNP derivative showed approximately 50% residual binding activity to nicotinic acetylcholine receptor (AChR)-rich membranes isolated from Torpedo californica and 50% of the lethality of alpha-BuTX. However, the activities were progressively lost as the accumulative modifications proceeded, and led finally to the formation of almost inactive penta-TNP derivative. The antigenicity of alpha-BuTX was still retained essentially intact after one or two amino groups of lysine residues were modified, whereas tri-TNP and CDNP-derivatives modified at Lys-38, 64 and 70 lost 46 and 70% of their antigenicity, respectively. Pronounced alteration in antigenicity was observed after five amino groups were trinitrophenylated. The present study indicates that the amino groups in alpha-BuTX may participate in the multipoint contact between the toxin and AChR, but none of the individual amino groups is definitely essential for the binding.

Amino Acids↗

Amino acid sequence of a phospholipase A2 from the venom of Trimeresurus gramineus (green habu snake).

Two phospholipases A2, named phospholipases A2-I and A2-II, were purified to homogeneity from the venom of Trimeresurus gramineus (green habu snake). The complete amino acid sequence of phospholipase A2-I was determined by sequencing the native protein and the peptides produced by enzymatic (Achromobacter protease I, clostripain, and chymotrypsin) and chemical (hydroxylamine) cleavages of the S-pyridylethylated derivative of the protein. The protein consisted of 122 amino acid residues and was similar in sequence to phospholipases A2 from the venoms of crotalid snakes which belong to the category of Group II. A most striking feature of this protein is that tyrosine at the 28th position which is common in phospholipases A2 and is assumed to be a part of the Ca2(+)-binding loop is replaced by phenylalanine. Such replacement is the first finding in Group II phospholipases A2. Secondary structure compositions of phospholipase A2-I are similar to those of Crotalus atrox phospholipase A2. No appreciable Ca2(+)-induced difference spectrum was observed, due probably to the absence of the effective chromophoric groups in the neighborhood of the Ca2+ binding site although Ca2+ is bound with affinity similar to that for T. flavoviridis phospholipase A2.

Amino Acid Sequence↗

High affinity antibody to cobrotoxin prepared from the derivatives of glutaraldehyde-detoxified cobrotoxin.

High affinity antibodies to cobrotoxin were obtained by immunization with derivatives of glutaraldehyde (GA)-modified cobrotoxin. The derivatives completely lost lethality and binding activity to nicotinic acetylcholine receptors (nAChR), but retained the same antigenicity as cobrotoxin toward anti-cobrotoxin antibody. Owing to hyperimmunization with these low toxicity derivatives, a high affinity antibody to cobrotoxin was induced in a short period. We also showed that the derivatives of cobrotoxin may have altered local conformation, and residues which contribute to the intensity of binding between antigen and antibody may consequently be exposed. Hence, the modified derivatives have increased binding affinity to anti-cobrotoxin antibody. In addition, since high affinity antibodies prepared using the derivatives exhibit more potent binding affinity to cobrotoxin than conventional anti-cobrotoxin antibody, the specific neutralizing capacity of the high affinity antibodies is greatly increased. These results lead to the conclusion that the derivatives of GA-modified cobrotoxin have the same antigenicity as the native toxin, and can be used as immunogens for the production of high affinity antibodies to cobrotoxin.

Amino Acid Sequence↗

Suppression of adrenal function in children on inhaled steroids.

Inhaled steroid therapy is one of the mainstays of treatment of asthma in children. Side effects, including suppression of the hypothalamic-pituitary-adrenal (HPA) axis, have been noted with high doses of inhaled steroids. Most studies concerning side effects have been done with mechanical nebulization devices or hand-held metered-dose inhalers. The present study attempts to ascertain if dry powder inhalation of beclomethasone dipropionate is associated with any significant suppression of the HPA axis. Fifteen children (10 male and 5 female) between the ages of 4 and 14 years were followed for several years in our outpatient department. They were on inhaled beclomethasone dipropionate at dosages ranging from 6.9 to 25 micrograms/kg per day for 4-24 months. The short adrenocorticotrophic hormone (ACTH) test was used to evaluate function of the HPA axis. Mild suppression of the HPA axis was noted in one of the cases. The study therefore concludes that at therapeutic doses of dry powder beclomethasone dipropionate, suppression of the HPA axis can occur. However, the extent of this complication does not appear to be greater than with hand-held or mechanical nebulization devices.

Administration, Inhalation↗

15-Hydroxyprostaglandin dehydrogenase activity in the lower genitourinary tract. A preliminary report.

In the pathway of prostaglandin inactivation, 15-hydroxyprostaglandin dehydrogenase (15-OHPGDH) has been proven to be the catalyst of the primary catabolic step in the oxidation of the 15-hydroxyl group into a 15-keto moiety in most derivatives of prostaglandins. In this study, we analysed 15-OHPGDH activity in the lower genitourinary tract. The specimens were obtained with permission from patients who underwent surgery. These specimens were then sent for quantitative determination using a tritium release assay specific for 15-OHPGDH. The highest enzyme activity was found in the ureter with a mean +/- SE (pmol/min/mg) of 94.99 +/- 51.00; the lowest activity was in the vas deferens, with a value of 0.18 +/- 0.21. This preliminary study indicated that the activity of 15-OHPGDH in the lower genitourinary tract was significant and that prostaglandin levels in the genitourinary tract may be regulated by this enzyme.

Adult↗

Run-down of neuromuscular transmission during repetitive nerve activity by nicotinic antagonists is not due to desensitization of the postsynaptic receptor.

1. Whether the function of the postsynaptic acetylcholine receptor is use-dependently affected by repetitive nerve stimulation in the presence of competitive antagonists was studied in the mouse phrenic nerve-hemidiaphragm preparation. 2. For electrophysiological experiments, the preparation was immobilized by synthetic mu-conotoxin, which preferentially blocks muscular Na-channels causing neither depolarization of the membrane potential, inhibition of quantal transmitter release, nor depression of nicotinic receptor function. 3. High concentrations of cobratoxin depressed indirect twitches and endplate potentials (e.p.ps) without inducing waning of contractilities or run-down of trains of e.p.ps evoked at 10-100 Hz. However, waning and run-down were accelerated after washout of the toxin despite diminished postsynaptic receptor blockade. Once the run-down of e.p.ps was produced by washout or low concentrations of cobratoxin, further depression of e.p.p. amplitude with high concentrations of cobratoxin did not attenuate the e.p.p. run-down. 4. The degrees of waning of tetanus and trains of e.p.ps produced by a very high concentration of tubocurarine (20 microM) were also less than that caused at a 100 fold lower concentration, albeit the amplitudes of twitches and the first e.p.p. were depressed more rapidly and markedly. 5. Tubocurarine, like cobratoxin, depressed the amplitude of miniature endplate potentials (m.e.p.ps) more than e.p.ps. 6. In contrast to the steepened run-down of successive e.p.ps in the presence of low concentrations of either nicotinic antagonists, the amplitude of m.e.p.ps observed during repetitive stimulation was uniform and was not different from that before stimulation. 7. The results suggest that the e.p.p. run-down and tetanic fade induced by nicotinic antagonists are due to a slow kinetic blockade of presynaptic receptors and confirm that the e.p.p. run-down is not produced by a use-dependent failure of postsynaptic nicotinic receptors. The roles of the presynaptic nicotinic receptor in positive or negative feedback modulations of transmitter release are discussed.

Acetylcholine↗

Factors influencing bacterial adherence to biomaterials.

The adherence of bacteria to implanted medical devices is believed to be important in the development of implant associated infections. Measures which reduce bacterial adherence should reduce the incidence of these infections. However, in order to assess the importance of adherence, the effectiveness of methods to reduce adherence, and compare data from different laboratories, the conditions of the in vitro studies on adherence need to be specified. There are currently no correct and incorrect methods, however, methods used need to be carefully described. The studies reported here indicate that the definition of adherence needs to be established, with the use of polystyrene as the reference material recommended. Since the adherent organisms lose adherence traits with culture, cultures must be selected for adherence regularly. It is important to control the number of organisms/ml but the volume used is not important. The medium used to grow the organisms and the use of stationary, rocking or flow conditions will alter adherence and need to be specified and be consistent within a set of experiments. Culture conditions, methods of rinsing the material, methods of elution and counting, or direct counting of organisms on the material need to be specified. Finally, as much information as possible on the bulk and surface properties of the material should be provided. The handling of the material for the experiments should be careful and defined. Fingerprints, contact with protein, wet surfaces vs dry surfaces, etc., will all affect the subsequent adherence. The materials should not be re-used since the removal of the adherent proteins or the biofilm is very difficult. Progress can be made in this important area if the details of procedures are specified.

Animals↗

Epidermal growth factor-related transforming growth factors in the urine of patients with hepatocellular carcinoma.

To characterize epidermal growth factor-related transforming growth factors in the urine of patients with hepatocellular carcinoma, gel filtration with Bio-Gel P-30 was performed in seven hepatocellular carcinoma patients and seven sex-matched and age-matched healthy controls. Distinct profiles of soft agar growth assay in the hepatocellular carcinoma patients and the normal controls were seen. Three peaks (A, B and C) in the urine were examined. Peak C in most hepatocellular carcinoma patients was higher than that in healthy controls. Similar profiles were detected with epidermal growth factor radioreceptor assay and cellular DNA synthesis assay. This result might indicate that transforming growth factors with low molecular weight were found in the urine of hepatocellular carcinoma patients. An exceptional HCC patient had an additional peak (A') that corresponded to the high molecular weight protein. We concluded that there were transforming growth factors with functional activity in the urine of patients with hepatocellular carcinoma.

Adult↗

Structural analysis of phospholipase A2 by near-IR Fourier transform Raman spectroscopy.

Venom toxins were isolated from Formosan cobra (Naja naja atra) by cation-exchange chromatography. Most toxin components could be obtained in relatively pure forms by single-step ion-exchange chromatography whereas an extra step of gel permeation was needed for the separation of phospholipase A2 (PLA2) from the major neurotoxic component, i.e. cobrotoxin. The newer near-IR FT-Raman analytical method has been applied to the characterization of PLA2 in their lyophilized forms. Structural analysis of PLA2 and correlation of Raman spectroscopic data with amino acid compositions were made. The results indicate that phospholipase A2 showed the Raman peak at 1659 cm-1 which is characteristic of the alpha-helical structure in this enzyme. It is also found that the relative Raman signal intensities of Tyr, Phe, Trp and Met residues in purified toxins correlate very well with the structural data obtained from amino acid analysis. The application of near-IR FT-Raman techniques in the detection of the microenvironments of the aromatic amino acids such as Tyr and Trp in the native toxins may prove useful in the investigation of the functional properties of various venom toxins.

Amino Acids↗