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Biomedical subjects

K J Chang

Publications and source records attributed to K J Chang.

At least 163 records · Page 9Linked to original sources
PubMed1992

Intrathecal pertussis toxin treatment attenuates opioid antinociception and reduces high-affinity state of opioid receptors.

The effect of pertussis toxin on opioid antinociception was studied in rats. Intrathecal injection of a single dose of pertussis toxin reduced the antinociceptive effect of PL017, a highly selective mu-opioid agonist, in a dose- and time-dependent manner. The maximal effective dose of pertussis toxin was 1 microgram, and the maximal effect was seen at day 3. The effect of the toxin lasted for 2 weeks, and the antinociceptive response recovered partially at the third week. The dose-response curves of the antinociceptive effect of PL017 were shifted to the right with increasing doses of pertussis toxin. Three days after pertussis injection, receptor-binding activity of membranes in the lumbosacral segment of spinal cords decreased to 70% of control as assayed by 125I-FK33824, a highly selective mu-receptor agonist. In experiments using [3H]naloxone as the radiolabeled ligand, displacement curves of FK33824 were shifted to the right after pertussis toxin treatment. The shift also was dose and time dependent. Scatchard analysis of binding data showed that, after pertussis toxin treatment, there was no significant change in the total number of binding sites, but a class of low-affinity binding sites appeared in addition to the high-affinity sites. When spinal membranes were washed in Na+ (100 mM) and guanosine diphosphate (100 microM) and binding was assayed in the presence of Mg2+ (5 mM), all the mu-receptors were in the high-affinity state in control membranes. After the pertussis toxin treatment, the ratio of low-affinity sites to high-affinity sites increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Continuous intrathecal opioid treatment abolishes the regulatory effects of magnesium and guanine nucleotides on mu opioid receptor binding in rat spinal membranes.

The regulatory effects of cations and guanine nucleotides on mu receptor binding after opioid drug and pertussis toxin treatment were studied in the rat spinal cord model. Continuous intrathecal (i.t.) infusion with PL017 for 5 days induced tolerance in a dose-dependent manner. Maximal tolerance was observed at day 2. A single i.t. dose (1 microgram) of pertussis toxin also induced tolerance to opioid. When mu receptor binding of the high-affinity sites was determined by 125I-FK33824, spinal membrane preparations from morphine- and pertussis toxin-induced tolerant animals demonstrated approximately 30% less binding than control membranes. Analysis of equilibrium competition binding of FK33824 against [3H]naloxone under a variety of experimental conditions (i.e., cations and guanine nucleotides) revealed differences among control and treated membranes. With Na+ (100 mM) + GDP (100 microM) pretreated membranes and binding assays conducted in the presence of Mg++, all mu receptors were observed to be in a high-affinity state in control membranes, whereas about 30% of receptors were in the low-affinity state in membranes from opioid- and pertussis toxin-treated animals. The increase in the proportion of low-affinity sites was dependent upon the infusion dose of PL017, and the increase correlated well with the degree of opioid tolerance developed. The regulatory effect of 5'-guanylylimidodiphosphate on opioid agonist binding was reduced in membranes from pertussis toxin- or opioid-treated animals. In binding assays conducted in the presence of Na+ (100 mM) + Mg++ (5 mM) + 5'-guanylylimidodiphosphate (30 microM) or Na+ (100 mM) + GDP (100 microM), all mu receptors in control membranes were in a low affinity-state, while those from opioid- or pertussis toxin-treated animals existed in both the high- and the low-affinity states. Continuous i.t. infusion with PL017 at the high dose of 1 microgram/hr for 5 days also decreased significantly (about 40%) the total number of receptors. These studies indicate that continuous opioid infusion and pertussis toxin treatment results in impairment in the receptor-G-protein coupling. This is reflected by the decreased regulatory effects of Mg++ and guanine nucleotides. Thus, in addition to receptor down-regulation, which is induced by PL017 at high doses, receptor-G-protein uncoupling may play a role in opioid tolerance induced by continuous infusion with morphine and PL017.

Animals↗
PubMed1992

The purification of nucleoside diphosphate kinase from rat brain.

Nucleoside diphosphate kinase from the cytosol of rat brain was purified to electrophoretic homogeneity through a series of chromatography columns, including DE-52, AcA-34 Ultrogel, phenyl-Sepharose and Q-Sepharose. The molecular weight of the enzyme was 64,000 as estimated by gel filtration, and it consisted of 3 identical 19,000 subunits. [35S]-GTP gamma S binding and autophosphorylation of the enzyme, and inhibition of the GTPase activity of G-protein were used to screen for the enzyme. These methods were shown to be useful for purifying and assaying the enzyme.

Animals↗
PubMed1992

Angiodysplasia as a source of intestinal bleeding: report of seven cases.

From October 1978 to April 1991, seven patients presenting at the National Taiwan University Hospital with gastrointestinal tract hemorrhage were diagnosed by colonofibroscopy or angiography as having angiodysplasia of the colon and small intestine. There were two men and five women; their ages ranged from 23 to 65 years, with a mean age of 50.3 years. None of these patients were diagnosed by barium enema. Only two patients were diagnosed by colonofibroscopy, and six patients were diagnosed by angiography. Therefore, angiography was the most effective method for diagnosing angiodysplasia. A vascular tuft was the most frequent finding. Six patients with lesions on the right side of the colon underwent a right hemicolectomy, one patient with a lesion on the jejunum underwent a right hemicolectomy initially with segmental resection of the jejunum later. The postoperative courses were smooth, and there has been no further evidence of gastrointestinal blood loss or anemia in the follow-up period. A right hemicolectomy is the treatment of choice because these lesions are frequently multiple; the lesions are found primarily on the right side of the colon.

Adult↗
PubMed1992

Surgery in cholangitis: bacteriology and choice of antibiotic.

Owing the frequent occurrence of intrahepatic stones in orientals, cholangitis presents a real problem. Surgery and antimicrobial drug therapy are the main forms of treatment. A retrospective study of choledochotomy, including biliary tract surgery, performed between July 1987 and June 1990, was conducted. Cases with negative common duct exploration during cholecystectomy were excluded. Among 186 cases, 128 (68%) had positive bile growth, which was defined as cholangitis. Sepsis-related complications occurred in 51 patients (27.4%), including 3 surgical deaths, 30 wound infections, and 18 others. The complication rate was higher in the cholangitis group than in the negative group (37.5% vs. 5.2%). However, if peri-operative antibiotics were effective against the cultured bacteria species, the complication rate was 16.9%; if not, the complication rate was 85.3%. For the different-generation cephalosporins used in the peri-operative period, the complication rates were 32.2%, 20.8%, and 27.6% each for 1st, 2nd, and 3rd generation cephalosporins, with no statistically significant differences. In microbiological study, polymicrobial infection was the rule. On average, 2.3 species were grown from each specimen. Enterococcus proved the most important species with a 54% culture rate. E. coli and Pseudomonas were important gram-negative bacilli, with culture rates of 46.1% and 39.1%, respectively. Anaerobic species were cultured in 12.3% of the patients. For good coverage of cholangitis prior to operation, the proper antibiotic should have potency against gram-positive Enterococcus, gram-negative bacilli, especially Pseudomonas and E. coli, and anaerobic species, especially Bacteroides.

Adult↗
PubMed1992

Identification of beta-subunit of GTP-binding regulatory protein in mitotic spindle.

BACKGROUND: The heterotrimeric GTP-binding regulatory protein (G protein) is important in membrane signal transduction. Since the function of the beta-subunit of G protein (G beta) in tumor cells is not well-documented, identification of G beta in tumor cells was performed. EXPERIMENTAL DESIGN: Immunolocalization, Western blotting, and immunoprecipitation of G beta in mammalian tumor and normal cells were investigated using rabbit antisera against amino and carboxyl terminal peptide fragments of G beta. A human nasopharyngeal carcinoma cell line (NPC-TW039) was used as the cell model because of its short doubling time. RESULTS: Anti-G beta immunoreactivity was found to be associated with the plasma membrane and the mitotic spindle throughout the mitotic phase of cell replication. Colcemid pretreatment resulted in random distribution of the anti-G beta reaction product in the mitotic cells. The same phenomenon was also seen in various other tumor and normal cell lines. When solubilized membranous, cytosolic, and mitotic spindle fractions were analyzed by Western blotting, G beta (35 +/- 1 kDa) was found to be associated with the plasma membrane and mitotic spindle fractions. Immunoprecipitation of isolated mitotic spindles with anti-G beta further confirmed these results. CONCLUSIONS: These findings indicate that G beta is closely associated with the mitotic spindle as well as the plasma membrane and may be important in regulation of cell mitosis in addition to transmembrane signal transduction.

Amino Acid Sequence↗
PubMed1991

Phorbol esters induce oscillatory contractions of intestinal smooth muscles.

The actions of tumor-promoting phorbol esters in smooth muscle excitation-contraction coupling were studied in isolated guinea pig ileum in the presence of various contractile agents. Muscarinic agonists, histamine and bradykinin elicited an initial transient phasic contraction and a subsequent sustained tonic contraction in guinea pig ileum. The Ca2+ channel antagonist nifedipine selectively inhibited the tonic contraction. Phorbol esters, protein kinase C activators, induced immediate muscle relaxation followed by oscillatory contractions when added during the tonic phase of contraction. Phorbol esters, when added in advance, slightly altered the ligand-induced phasic contraction but converted tonic contractions into oscillatory spikes. The amplitude, frequency and shape of the oscillation induced by phorbol esters were dependent upon the dose of phorbol ester: amplitude was increased and frequency was decreased by increasing the doses of phorbol ester. In contrast, the phorbol ester potentiated the tonic contraction induced by high potassium chloride with little effect on the phasic component. It also sensitized the muscles to Bay K 8644. Bay K 8644, which was ineffective in stimulating muscle contraction at 1 nM, became a very effective stimulator in the presence of the phorbol ester. All of these phorbol ester-induced potentiations and oscillations were sensitive to inhibition by staurosporine or nifedipine. These data suggest that in guinea pig ileum, protein kinase C plays a positive regulatory role in Ca2+ channel activation and promotes a complex regulatory effect on Ca(2+)-mobilizing ligand-stimulated Ca2+ channel activity, which results in oscillatory contractile responses to carbachol, methacholine, histamine and bradykinin.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Ingestion of eicosapentaenoic acid-ethyl ester renders rabbit LDL less susceptible to Cu2(+)-catalyzed-oxidative modification.

The present study revealed that low density lipoprotein (LDL) obtained from rabbits fed highly purified eicosapentaenoic acid-ethyl ester (EPA-E) (EPA-LDL) was significantly less susceptible to oxidative modification catalyzed by Cu2+ as compared to LDL from rabbits fed a normal diet (control LDL). In a comparison of fatty acid composition of LDL, the contents of EPA and docosapentaenoic acid were significantly increased in EPA-LDL as compared to control LDL. The content of arachidonic acid (AA) was the same in both LDL groups. The contents of total cholesterol, free cholesterol, triglyceride, and phospholipid in LDL were unchanged by EPA-E ingestion. These data raise the possibility that EPA may protect LDL from oxidative modification, leading to a reduction of oxidized LDL in atherosclerotic lesions, and that this may be how EPA exert its anti-atherosclerotic action.

Animals↗
PubMed1991

Inhibition of ras-induced germinal vesicle breakdown in Xenopus oocytes by rap-1B.

A cDNA clone (Krev-1) has recently been identified that possesses the ability to reverse the transformed phenotype when introduced into a K-ras-transformed NIH/3T3 cell line. The Krev-1 protein, also known as rap-1A, was found to share 50% homology with the ras proteins. The rap-1A protein has also been shown to block the interaction of ras with its GTPase activating protein in vitro, leading to speculation regarding its role in vivo. A closely related protein, rap-1B, has also been identified in platelets, human erythroleukemia cells, neutrophils, and aortic smooth muscle cells. Unlike rap-1A, rap-1B has been shown to be phosphorylated in platelets. Given the high degree of similarity between the amino acid sequences of rap-1A and rap-1B, we sought to investigate the effect of microinjected rap-1B on H-ras(Val12)-induced germinal vesicle breakdown in Xenopus laevis oocytes. In this assay system, equimolar concentrations of rap-1B were found to block germinal vesicle breakdown triggered by the oncogenic ras protein. However, in the presence of IGF-1, this inhibition was not observed. Moreover, rap-1B is readily phosphorylated in the oocytes.

Animals↗
PubMed1991

Role of 5-lipoxygenase products of arachidonic acid in cell-to-cell interaction between macrophages and natural killer cells in rat spleen.

In the present study we performed experiments to reveal the role of 5-lipoxygenase products of arachidonic acid in cell-to-cell interaction between rat peritoneal macrophages and spleen natural killer (NK) cells. Peritoneal macrophages were found to significantly enhance NK cell activity. It was found that the enhancing activity of macrophages was significantly inhibited by the ingestion of highly purified eicosapentaenoic acid-ethyl ester (EPA-E). But direct cytotoxic action of macrophage on target cells (YAC-1) was unchanged by the ingestion of EPA-E. In addition, the depressed enhancing activity of EPA-enriched macrophages (EPA macrophages) was partially, but significantly, restored by the addition of either 10(-10) M leukotriene B4 (LTB4) or 10(-12) M 5-hydroperoxyeicosatetraenoic acid (5-HPETE). The partial restoring effect of 10(-10) M LTB4 was further significantly enhanced by the addition of 5-HPETE. In contrast 5-hydroxyeicosatetraenoic acid (5-HETE) had no modulatory effect on the depressed activity of EPA macrophages. LTB4, 5-HPETE, and 5-HETE had no direct effect on NK cell activity itself. Significantly less amounts of LTB4 and 5-HETE were produced in EPA macrophages as compared with that in control macrophages. The present study indicates that macrophage modulatory action on NK cells can be partly mediated by LTB4 and 5-HPETE, which are produced in macrophages.

Animals↗
PubMed1991

A role for the interferon response DNA sequence in directing transcription of the T18d Tla gene.

T18d of BALB/c mice is a member of the Tla category of class I genes of the major histocompatibility complex of the mouse and is highly restricted in expression. Deletion analysis implies that an element essential to T18d expression resides within the region -4 to +54. The homologous region of T3d, a Tla gene which normally is not expressed in BALB/c mice, also has promoter activity. Thus the expressibility of T18d vs T3d is unlikely to be due to sequence differences in this region. A DNA-binding protein, factor VI, was found to bind to the region -33 to +54. DNase I footprinting analysis indicated that the DNA fragment 5'-ACTATAGTTTCACTTTTT-3' (+3 to +20) was protected by factor VI. This region includes the interferon response sequence (IRS). Homologous DNA segments of other class I genes, Ld and Dd, competed for factor VI in DNA-protein binding assay with lower affinity as compared with T18d. In mutation analysis, the 3' portion of the IRS is more important than the 5' portion with respect to binding affinity of factor VI and to transcriptional activity in transfected cells. This result signifies a role of IRS in T18d transcription and suggests that the mechanism of T18d transcription might be unusual.

Animals↗
PubMed1991

Properties of the promoter region of the T18d (T13c) Tla gene.

The T18d (formerly T13c) gene of BALB/c mice belongs to the category of Tla genes which is expressed by both thymocytes and TL+ T-cell leukemias. To elucidate the regulation of T18d, different restriction fragments of the 5' flanking region between -457 and +146 were linked to the chloramphenicol acetyltransferase (CAT) gene and transfected into TL+ and TL- cells. By comparison of transiently expressed CAT activity among cells transfected with different CAT constructs, the results suggest that determination of TL+ vs TL- phenotypes is located within the region -105 to -33, and that an element essential to T18d expression resides within the region -33 to +54. Putative DNA-binding factors characterizing particular cell types and displaying selective affinity for particular T18d restriction fragments were identified by electrophoretic mobility shift assays with nuclear extracts (NEs). Two factors (or complexes) which bound specifically to the T18d fragment -105 to -33 were expressed preferentially in TL+ cells and thus may be involved in determining the tissue-selective expression of T18d. The close proximity of negative and positive cis-acting elements within the promoter region is consistent with regulation of T18d gene expression by a variety of trans-acting factors whose production is attuned to development and differentiation. The data provided may serve as a guide to study the regulation of other categories of Tla genes that are normally silent in thymocytes but may become expressed by leukemia cells.

Animals↗
PubMed1991

Urea gradient/SDS-PAGE; a useful tool in the investigation of signal transducing G proteins.

We describe an updated and improved protocol to perform urea gradient/SDS-PAGE in which proteins are electrophoresed through 9% polyacrylamide gel slabs in the presence of a linear 4 M to 8 M gradient of urea using Laemmli's separation buffers. We provide examples of this technique to separate PTX labeled G protein alpha subunits, as well as unlabeled alpha and beta subunits of G proteins. Applications of the technique are exemplified in which (1) the chromatographic separations of G proteins in DEAE-Toyopearl and MonoQ columns are compared, (2) the complexity of PTX substrates expressed in human erythrocytes, bovine brain, dog ventricle, FRTL-5 cells, HIT cells, GH4C1 cells and RIN cells are compared, and (3) the polypeptide composition of G protein beta gamma subunits, as expressed in several tissues and found in three distinct G proteins from a single cell population, are analyzed.

Adenosine Diphosphate Ribose↗
PubMed1991

Primary malignant tumor of the small intestine.

The records of 101 patients with primary small intestinal malignant tumor at NTUH, collected from 1960 to 1989, were reviewed. These patients represented 1.2% of the patients with gastrointestinal cancer at NTUH over the same period. Fourty-two (41.6%) of the cancer patients had lymphomas, 30(29.7%) had adenocarcinomas, 26 (25.7%) had leiomyosarcomas, and 3(3.0%) had carcinoid tumors. The average age at cancer presentation was 47.5 years (range from 3 to 96). The lymphoma patients had an average age of 35.1 years, while adenocarcinoma patients averaged 60.4 years of age. Leiomyosarcoma and carcinoid tumors averaged 51.2 years and 59 years, respectively. There were 65 male patients and 36 female patients, and there was a male predominance in all groups except for the leiomyosarcoma group which had an equal sex ratio. Generally speaking, the incidence rate for the areas involved were similar in the duodenum, jejunum and ileum. However, adenocarcinomas were more common in the duodenum (53%) and 45% of lymphomas were found in the ileum, as were the carcinoid tumors (66%). The most common presenting symptom was abdominal pain (62%), with bleeding second (32%). Obstruction and palpable mass together were present in 29% of the cases. Body weight loss was found in 25% of patients, and 14% of the patients presented with acute abdomen due to intestinal perforation. Laparotomy was the most common diagnostic procedure (60%). Preoperative diagnoses were possible in cases of duodenal and upper intestinal malignancies, but were rarely possible in patients with lower intestinal malignancies. Sixty-eight patients (68%) underwent tumor resection for palliation or cure. The operation mortality was 4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Aneurysm arising from the branch of the superior mesenteric artery.

Superior mesenteric branch aneurysms are rare and usually become symptomatic at the time of rupture. Pain, gastrointestinal blood loss and intra-abdominal hemorrhage draw attention to the presence of aneurysms in 70% of the reported cases. We report on a 64-year-old male patient who had an emergent laparotomy for acute abdominal pain at a local hospital in Changhua in March of 1988. The operative finding was an unresectable mesentric mass, and the pathologic finding of the biopsy was a chronic abscess. Because of two episodes of tarry stools after the operation, the patient was referred to the National Taiwan University Hospital for further evaluation of the intra-abdominal mass. After admission in April of 1990, abdominal sonogram and CT examinations demonstrated the presence of a multilobulated mass which was suspected to be an aneurysm. Selective superior mesenteric arteriography confirmed this diagnosis and showed that the aneurysm arose from the origin of the ileocolic branch. At surgery, the aneurysm was found to have a fistula tract communicating with the terminal ileum. The aneurysm and the associated segment of the terminal ileum were successfully removed. We herein report this unusual case.

Aneurysm↗
PubMed1991

Factors affecting local or regional recurrence in breast cancer.

Between 1975 and 1989, 535 patients with infiltrating ductal carcinoma of the breast in various clinical stages were treated by modified radical mastectomy and axillary node clearance, followed by chemotherapy, endocrine therapy or radiotherapy. Median follow-up was 3 years (5 months to 15 years). Fifty-eight local or regional recurrences occurred. The 5-year and 10-year actuarial risks of breast recurrences were 14% +/- 2% and 23% +/- 4%, respectively. Using multivariate analysis with the Cox regression model, the most important multivariate-adjusted independent contributing factors to local or regional breast recurrences were age less than or equal to 40 (p less than 10(-4), relative risk = 2.94), positive lymph nodes greater than 3 (p less than 10(-3), relative risk = 2.57), and multicentricity (p = 0.044, relative risk = 2.73). The overall 5-year survival rate of recurrent patients was 64 +/- 7%, and was significantly worse when breast recurrence occurred in the first 18 months after operation. The multivariate-adjusted relative risk of death for early recurrence was 4.35 (p = 0.04). The unadjusted 5-year survival rate for early recurrence was 58% +/- 1%, and 85% +/- 8% for late recurrence. This study confirms the relationship between young age and low breast control rates. It emphasizes the adverse prognosis of early breast recurrences as compared to the relatively favorable outcome of late recurrences.

Adult↗
PubMed1991

Tumoricidal activity of interferon-r activated peripheral monocytes in colorectal cancer patients.

Peripheral blood monocytes obtained from 8 colorectal cancer patients and 6 normal controls were incubated in vitro with interferon-r (IFN-r) in the presence of bacterial lipopolysaccharide (LPS). The cytotoxic properties of the monocyte were determined subsequent to the interaction with radiolabeled autologous, allogeneic, as well as cultured colorectal cancer cells. Monocytes from normal controls and all colorectal cancer patients were activated in vitro to become tumoricidal; monocytes lysed tumorigenic cells but not nontumorigenic cells. Activators of protein kinase C (e.g. phorbol esters, PMA) and Ca2+ ionophores (A23187) when added alone did not effect the activation state of the monocyte. Whereas, PMA and A23187 cooperatively reproduced the ability of IFN-r to prime monocytes for tumoricidal activity. In the presence of PMA, A23187, and EGTA, the addition of excessive Ca2+ was sufficient for priming, whereas the addition of excessive Mg2+ was much less efficient. Priming by IFN-r, however, was not blocked by EGTA. An efflux of Ca2+ from preloaded monocytes was significantly increased by A23187 and by IFN-r. Quin-2/AM, an intracellular chelator of Ca2+, blocked priming by IFN-r. The results suggest that priming of monocytes for tumoricidal function by IFN-r may be involved in the activation of protein kinase C and mobilization of intracellular Ca2+.

Aged↗