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Biomedical subjects

K Chang

Publications and source records attributed to K Chang.

At least 73 records · Page 4Linked to original sources
PubMed1996

Plasminogen activator activity is decreased in rat gingiva during diabetes.

Diabetes produces extensive alterations of collagen metabolism including enhanced gingival collagenase activity. However, the mechanism for this enhanced enzyme activity is unclear. Collagenase is secreted from cells in a latent form and plasmin has been proposed as an important in vivo activator of procollagenase. Plasmin is converted from its precursor, plasminogen, by the proteolytic action of a serine proteinase, plasminogen activator (PA). The current study was therefore undertaken to determine the effect of diabetes on gingival PA activity in the rat. Since doxycycline is a potent collagenase inhibitor, the effect of doxycycline on gingival PA activity was also investigated. Eighteen male, Sprague-Dawley rats were made diabetic by streptozotocin injection (7 mg/100 g). Control rats (N = 8) were sham-treated. Doxycycline (5 mg/day/rat) was administered to 9 of the 18 diabetic rats by gavage on a daily basis. The other 9 diabetic rats were administered with saline. After 3 weeks, blood and gingival tissue were collected from each rat for the determination of glucose level and gingival PA activity. The tissues were then minced and extracted with 5 mM sodium phosphate containing 1% Triton X-100. PA assay was performed using chromatogenic substrate to determine PA activity in the extracts. Gingival PA activity in the diabetic rats was significantly reduced compared to the control (13.5 +/- 1.6 vs. 36.0 +/- 3.3 microunits/100 micrograms protein, P < 0.01). Doxycycline administration to diabetic rats had no effect on the already reduced gingival PA activity (10.4 +/- 3.5 in doxycycline-treated rats vs. 13.5 +/- 1.6 mu units/100 micrograms protein in untreated diabetic rats). PA activities in gingival tissues from the diabetic, nondiabetic control and doxycycline-treated diabetic groups were also demonstrated on zymographs as lytic bands. Regarding the well-known fact that gingival collagenase activity is enhanced during diabetes, our results did not support the notion that this biochemical alteration is attributed to increased activation of procollagenase by PA.

Animals↗
PubMed1996

Laboratory diagnosis of Helicobacter pylori infection by polymerase chain reaction.

Although the detection of Helicobacter pylori (Hp) infection is important, it is a rather difficult task using only conventional diagnostic techniques. In this study, we have applied a polymerase chain reaction (PCR)-based assay for the diagnosis of Hp infection. RT-PCR for Hp ribosomal RNA was utilized, using the gastric biopsy specimens obtained endoscopically from 10 patients. PCR primers have been designed from the highly consensus region of the 7 different Hp rRNA sequences in GenBank. In the detection of Hp, PCR was more sensitive than culturing and showed 100% of the sensitivity and specificity compared with histology. Our primer pair could detect as few as 50 organisms per reaction. RT-PCR for Hp rRNA is a sensitive and specific method to detect Hp infection in the gastric mucosa.

Base Sequence↗
PubMed1996

[Psychiatric emergency consultation in a general hospital].

Inpatients in general hospital often presented with psychological problems and some of them need emergent psychiatric interventions. However, there have been little attention on the psychiatric emergency consultation. The purpose of this paper is to review the psychiatric emergency service in a general hospital over 3-year period. During this period, there were 88 psychiatric emergency consultations that represented 2.3% of all psychiatric consultations. The emergency group showed no difference in sex and age, but received more diagnoses of delirium (58.0%) than the other referrals. About one fourth of these patients had psychiatric history. Stated requests for "agitation and irritability", "psychiatric symptoms" and "uncooperation with treatment" were the most frequent reasons. Sixty-five percent of the patients receive recommendations of medication treatment. Among them, neuroleptics and anxiolytics were most common used. About one half of the patients needed further medical tests. After psychiatric interventions, most of the patients got improved within 2 days but 15 patients died during hospitalization. These findings indicated that psychiatric emergency consultation though the request rate is low. When making diagnoses in emergency consultation, past psychiatric history is important and organic mental disorders should be ruled out first. After psychiatric interventions, most of the psychiatric emergency could be improved. It suggested that the setting of psychiatric emergency consultation could improve the quality of patient care in a ageneral hospital.

Adolescent↗
PubMed1995

Molecular cloning and functional analysis of a novel P2 nucleotide receptor.

The cDNA encoding a novel P2 receptor was isolated from rat aortic smooth muscle cell library and functionally characterized. The cloned P2 receptor exhibits structural features characteristic of the G protein-coupled receptor family and shows 44 and 38% amino acid identity with previously cloned rat P2U and chicken P2Y receptors, respectively. The cloned P2 receptor is functionally coupled to phospholipase C but not to adenylate cyclase in C6 rat glioma cells transfected with the cloned P2 expression vector. The rank order of agonist potency as judged by intracellular Ca2+ mobilization responses is UTP > ADP = 2-methylthioATP > ADP beta S > ATP = ATP gamma S, which is not compatible with any of the previously characterized P2 receptor subtypes. The nonselective P2 antagonists, suramin and reactive blue-2, inhibit nucleotide-induced phospholipase C activation in cells expressing the cloned P2 receptor. The cloned P2 receptor mRNA is abundantly expressed in various rat tissues including lung, stomach, intestine, spleen, mesentery, heart, and, most prominently, aorta. The results indicate that the novel metabotropic P2 receptor has pharmacological characteristics distinct from any of P2 receptor subtypes thus far identified and suggest the existence of a novel regulatory system by extracellular nucleotides of potential significance.

Adenine Nucleotides↗
PubMed1995

Perfused Kupffer cell mass. Correlation with histology and severity of chronic liver disease.

The perfused Kupffer cell mass determines sulfur colloid distribution by liver spleen scan (LSS) and is proportional to the perfused hepatocyte mass. This accounts for the correlation of sulfur colloid distribution with tests of hepatic function and raises the question of whether the LSS can be used as a quantitative test of hepatic function. The recent ability to precisely measure sulfur colloid distribution by single-photon-emission computerized tomography (SPECT) prompted us to evaluate the clinical value in 329 consecutive patients with adequate LSS and clinical information, of which 27 apparent normals and 220 patients with chronic liver disease (CLD) were included in this study. The liver-bone marrow index (LBI) indicated the distribution of counts between the liver and bone marrow. The liver-spleen index (LSI) indicated the distribution between liver and spleen adjusted for spleen size. The LBI and LSI correlated with each other (r = 0.753; P < 0.001). The arithmetic mean of LBI and LSI was defined as the severity score. Detailed clinical evaluation was available in these patients and included 109 who had liver biopsy. A severity score in 27 normals was 102 +/- 5 (mean +/- SD) with all values > 85. The severity score correlated with hepatic fibrosis (r = -0.694; P < 0.001) in 109 patients with benign liver disease who had recent biopsies and with the Child-Pugh classification (r = 0.78; P < 0.001) in 220 patients with CLD.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1995

Inhibition of sorbitol dehydrogenase. Effects on vascular and neural dysfunction in streptozocin-induced diabetic rats.

These experiments were undertaken to assess the role of sorbitol dehydrogenase in mediating sorbitol pathway-linked neural and vascular dysfunction in rats with streptozocin-induced diabetes. 2-methyl-4-[N,N-dimethylsulfamoyl-piperazino]-pyrimidine (S-0773), a putative inhibitor of sorbitol dehydrogenase, was given in the drinking water to control and diabetic rats. After 5 weeks of diabetes, glycosylated hemoglobin levels were increased twofold and were unaffected by S-0773. Sorbitol levels in diabetic rats were increased 11- to 14-fold in ocular tissues and sciatic nerve; S-0773 increased sorbitol levels another 4-fold or more in these same tissues but had much smaller effects in other tissues. Diabetes-associated increases in fructose levels and lactate:pyruvate ratios in retina and in sciatic nerve were markedly attenuated by S-0773. S-0773 also attenuated, but did not completely normalize, impaired caudal nerve conduction and vascular dysfunction in ocular tissues, sciatic nerve, and aorta in diabetic rats. These observations, together with other evidence, suggest that sorbitol pathway-linked vascular dysfunction (in ocular tissues, peripheral nerve, and aorta) and electrophysiological dysfunction (in peripheral nerve) induced by diabetes are more closely linked to increased oxidation of sorbitol to fructose than to putative osmotic effects of elevated sorbitol levels or redox and metabolic imbalances associated with reduction of glucose to sorbitol by aldose reductase.

Animals↗
PubMed1995

The regulatory effect of nucleoside diphosphate kinase on G-protein and G-protein mediated phospholipase C.

The effect of nucleoside diphosphate kinase (NDPK) on the activity of guanine nucleotide regulatory protein (G-protein) mediated phospholipase C (PLC) and on the [35S] GTPT tau S binding of G-protein was investigated in this work in order to demonstrate the mechanism behind the regulation of G-protein and its effector PLC by NDPK. The stimulation of PLC in turkey erythrocyte membrane by both GTP and GTP tau S indicated that the PLC stimulation was mediated by G-protein. NDPK alone stimulated PLC activity, as well as the stimulation in the presence of GTP and GDP, in a dose-dependent manner. However, NDPK inhibited GTP tau S-stimulated PLC. Furthermore, NDPK inhibited [35S]GTP tau S binding of purified Gi-protein in a non-competitive manner. A hypothesis implying an important role of direct interaction of G-protein and NDPK in the regulation of their functions is suggested and discussed.

Animals↗
PubMed1995

Effect of monocular blockade of retinal activity on the development of visual callosal connections in the rat.

It has been previously reported that neonatal monocular enucleation in rats and hamsters induces the development of an anomalous band of callosal connections in the middle of area 17 (primary visual cortex) in the hemisphere ipsilateral to the remaining eye. In order to determine whether this effect is due to elimination of retinal activity in one eye, we used the anatomical tracer horseradish peroxidase (HRP) to study the pattern of visual callosal connections in rats in which retinal activity had been blocked by intraocular injections of tetrodotoxin during the first two weeks of life. We found that the callosal pattern in the hemisphere ipsilateral to the eye not treated with tetrodotoxin was not distinguishable from the pattern present in normal rats. In particular, we did not observe the anomalous extra band of callosal connections that occurs in area 17 in the hemisphere ipsilateral to the remaining eye in monocularly enucleated rats. These results indicate that blockade of retinal activity in one eye is not sufficient to cause the marked changes in the pattern of visual callosal connections that are induced by neonatal monocular enucleation.

Animals↗
PubMed1994

Molecular cloning and expression of a cDNA encoding a protein detected by the K1 antibody from an ovarian carcinoma (OVCAR-3) cell line.

MAb KI recognizes a cell-surface glycoprotein (MW approximately 40 kDa) present in ovarian carcinomas, malignant mesotheliomas, squamous-cell carcinomas and normal mesothelial cells. In this study, expression screening was used to isolate cDNA clones encoding an antigen recognized by MAb KI from a cDNA library made from a human ovarian carcinoma cell line (OVCAR-3). Subsequently, other clones were isolated by DNA hybridization using a cDNA probe derived from one of the initial clones. The sequence of all the clones was similar. The longest cDNA contains 2,444 base pairs, and encodes a polypeptide of 263 amino acids with a calculated molecular weight of 30,511 daltons. The nucleotide sequence and deduced amino-acid sequence of the protein show no homology to other sequences in current data bases. In vitro translation of RNA transcripts from the cDNA inserts yielded polypeptides of 29 and 30 kDa. Similar-sized proteins were obtained upon expression of the cDNA in Escherichia coli, and these proteins were reactive with MAb KI. The protein(s) expressed in E. coli were purified and used to make rabbit or mouse antisera. These antisera reacted strongly with a soluble cytosolic protein in OVCAR-3 cells, but not with the membrane-bound antigen. Soluble cytosolic proteins of a similar size, recognized with MAb KI, were found in OVCAR-3 and N87 (gastric cancer) cells but not in 10 other cancer cell lines. These data indicate that the cloned cDNA encodes a cytosolic protein that reacted with MAb KI. This soluble protein is expressed only in cells containing the CAKI surface glycoprotein, suggesting that the 2 proteins could be structurally related.

Amino Acid Sequence↗
PubMed1994

Presence of hepatitis B and C viral genomes in US blood donors as detected by polymerase chain reaction amplification.

Hepatitis C virus (HCV) represents a major cause of posttransfusion hepatitis worldwide. Posttransfusion hepatitis associated with hepatitis B virus (HBV) continues to occur. HBsAg-negative donor sera from the Rhode Island Blood Center between 1987 and 1988 were screened using more sensitive techniques to assess the prevalence of low level HBV infection. Group I consists of 866 healthy blood donors without HBV serologic markers, group II consists of 377 donors with ALT elevations (> 45 IU/L), group II consists of 148 donors positive for anti-HBc, and group IV consists of eight donors positive for both surrogate markers. A sensitive monoclonal immunoradiometric assay (M-IRMA) was employed for detection of HBsAg-associated epitopes (detection limit of 20 pg/ml) in serum. A subset of sera were analyzed for the presence of HBV DNA using the method of anti-HBs capture of HBV related virions in serum followed by polymerase chain reaction (PCR) amplification. Using these techniques, 0.8% and 1.7% of donors were positive for HBsAg and HBV DNA respectively in group I. In contrast, 0.9% and 9.5% in group II and 0.7% and 18.1% in group III were positive, respectively. There were eight donors with both ALT elevation and anti-HBc; and four (50%) of these were positive for HBV DNA. In the group with anti-HBc, the majority (80%) of donors with HBV DNA had either no or low (signal to noise ratio < 10) anti-HBs titer. Using anti-HCV testing and reverse transcription-PCR for detection of HCV genomes, we detected evidence of HCV infection in nine of the 49 donors with low level HBV DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Donors↗
PubMed1994

In vitro anti-Mycobacterium avium activities of quinolones: predicted active structures and mechanistic considerations.

The relationship between the structures of quinolones and their anti-Mycobacterium avium activities has been previously derived by using the Multiple Computer-Automated Structure Evaluation program. A number of substructural constraints required to overcome the resistance of most of the strains have been identified. Nineteen new quinolones which qualify under these substructural requirements were identified by the program and subsequently tested. The results show that the substructural attributes identified by the program produced a successful a priori prediction of the anti-M. avium activities of the new quinolones. All 19 quinolones were found to be active, and 4 of them are as active or better than ciprofloxacin. With these new quinolones, the updated multiple computer-automated structure evaluation program structure-activity relationship analysis has helped to uncover additional information about the nature of the substituents at the C5 and C7 positions needed for optimal inhibitory activity. A possible explanation of drug resistance based on the observation of suicide inactivation of bacterial cytochrome P-450 by the cyclopropylamine moiety has also been proposed and is discussed in this report. Furthermore, we confirm the view that the amount of the uncharged form present in a neutral pH solution plays a crucial role in the drug's penetration ability.

4-Quinolones↗
PubMed1994

Endotoxin-induced uveitis in the rat is attenuated by inhibition of nitric oxide production.

PURPOSE: These experiments were undertaken to assess the role of increased nitric oxide production in the pathogenesis of vascular dysfunction associated with endotoxin-induced uveitis. METHODS: Lipopolysaccharides (LPS) (100 micrograms of Salmonella minnesota) was injected into foot-pads of Lewis rats randomly assigned to an untreated group or to a group treated with subcutaneous injections of aminoguanidine, a selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS). Controls included untreated and aminoguanidine-treated rats. Twenty to 24 hours later, blood flow and vascular 125I-albumin permeation were quantified in ocular tissues. Eyes were graded histologically for leukocyte infiltration into the anterior uvea and anterior chamber, and leukocyte counts were performed on aqueous fluid. Plasma nitrate levels were measured fluorometrically after enzymatic reduction to nitrite. RESULTS: Lipopolysaccharides markedly increased plasma nitrate levels and 125I-albumin permeation in aqueous fluid, retina, anterior uvea, and choroid-sclera. Blood flow was increased only in the anterior uvea. Aminoguanidine normalized plasma nitrate levels and prevented or significantly ameliorated the 125I-albumin permeation and blood flow changes in ocular tissues. The increased aqueous fluid content of lymphocytes and neutrophils in LPS-treated rats, as well as the increased histologic score of iritis, were significantly reduced by aminoguanidine. CONCLUSIONS: These results suggest that the hemodynamic and vascular permeability changes associated with endotoxin-induced uveitis are mediated in large part by increased production of nitric oxide.

Albumins↗
PubMed1993

Inhibition of nitric oxide formation by guanidines.

Aminoguanidine, N,N'-diaminoguanidine, methylguanidine, and 1,1-dimethylguanidine were compared to NG-monomethyl-L-arginine (L-NMMA) for their ability to inhibit nitric oxide (NO) formation by cytokine-inducible and vascular constitutive isoforms of NO synthase. These comparisons were performed by assessing (1) cytokine-induced production of nitrite by RINm5F cells, (2) vasoconstrictor responses of isolated rat mesenteric arteries, and (3) in vivo blood pressure responses following intravenous bolus injection into anesthetized rats. Aminoguanidine and L-NMMA were the most potent inhibitors of cytokine-induced NO formation in RINm5F cells, while the other guanidine compounds were 10 (1,1-dimethylguanidine) to 100 (methylguanidine) times less potent. L-NMMA and 1,1-dimethylguanidine were the most potent inhibitors of the vascular constitutive isoform of NO synthase in both assay systems, while aminoguanidine and N,N'-diaminoguanidine were the least potent. These results (1) confirm the selective inhibition of the inducible isoform of NO synthase by aminoguanidine, (2) indicate that N,N'-diaminoguanidine, while approximately 30 times less potent than aminoguanidine in inhibiting inducible NO synthase, has very little effect on constitutive NO synthase activity, and (3) 1,1-dimethylguanidine, like L-NMMA, is a relatively potent inhibitor of both isoforms of NO synthase.

Amino Acid Oxidoreductases↗
PubMed1993

Prevention of diabetic vascular dysfunction by guanidines. Inhibition of nitric oxide synthase versus advanced glycation end-product formation.

This study was undertaken to compare the ability of two guanidine compounds (aminoguanidine and methylguanidine), with different in vitro effects on NO synthase activity and AGE formation, to inhibit diabetic vascular dysfunction developing early after the onset of diabetes. In rats with STZ-induced diabetes of 5-wk duration, regional vascular [125I]albumin permeation was increased about two- to threefold in ocular tissues, sciatic nerve, and aorta; in general, both guanidine compounds normalized albumin permeation in diabetic rats without affecting it in controls. Methylguanidine was only approximately 7% as effective as aminoguanidine as an inhibitor of AGE formation from L-lysine and G6P; both compounds were poor inhibitors of AR. Methylguanidine was approximately 1-5% as potent as aminoguanidine and L-NMMA as an inhibitor of the cytokine- and endotoxin-inducible isoform of NO synthase. In contrast, the potency of methylguanidine as an inhibitor of the constitutive isoform of NO synthase was comparable to that of aminoguanidine, and both guanidine compounds were much less effective than L-NMMA. These observations suggest a role for a relative or absolute increase in NO production in the pathogenesis of early diabetic vascular dysfunction and raise the possibility that inhibition of diabetic vascular functional changes by aminoguanidine may reflect inhibition of NO synthase activity rather than, or in addition to, prevention of AGE formation.

Aldehyde Reductase↗
PubMed1993

Hyperglycemic pseudohypoxia and diabetic complications.

Vasodilation and increased blood flow are characteristic early vascular responses to acute hyperglycemia and tissue hypoxia. In hypoxic tissues these vascular changes are linked to metabolic imbalances associated with impaired oxidation of NADH to NAD+ and the resulting increased ratio of NADH/NAD+. In hyperglycemic tissues these vascular changes also are linked to an increased ratio of NADH/NAD+, in this case because of an increased rate of reduction of NAD+ to NADH. Several lines of evidence support the likelihood that the increased cytosolic ratio of free NADH/NAD+ caused by hyperglycemia, referred to as pseudohypoxia because tissue partial pressure oxygen is normal, is a characteristic feature of poorly controlled diabetes that mimics the effects of true hypoxia on vascular and neural function and plays an important role in the pathogenesis of diabetic complications. These effects of hypoxia and hyperglycemia-induced pseudohypoxia on vascular and neural function are mediated by a branching cascade of imbalances in lipid metabolism, increased production of superoxide anion, and possibly increased nitric oxide formation.

Animals↗
PubMed1993

Helicobacter pylori toxin inhibits growth and proliferation of cultured gastric cells-Kato III.

The presence of Hp is strongly associated with chronic type B gastritis and peptic ulcer disease. The pathogenic mechanisms of Helicobacter pylori (Hp) infection are still unclear. Hp produces toxins which are capable of exerting cytotoxic effects. Whether these changes result in decreased cell proliferation has not been previously demonstrated. Our results show that a 2 hour incubation of gastric Kato III cells with Hp cytotoxin produces a 60% decrease in cell proliferation. In conjunction with a decreased cell proliferation, cell growth is also decreased on days 5 and 7. The ability of Hp to retard cell proliferation may play a role in the pathogenesis of Hp-associated diseases by inhibiting the normal mechanisms of gastric mucosal protection and repair.

Bacterial Proteins↗
PubMed1992

Frequent expression of the tumor antigen CAK1 in squamous-cell carcinomas.

K1 is a murine monoclonal antibody (MAb) derived from a hybridoma generated by the fusion of splenocytes of BALB/c mice immunized with a human ovarian tumor cell line, OVCAR-3. This antibody reacts strongly with epithelial ovarian tumors and mesotheliomas. The antigen recognized by MAb K1, designated CAK1, has recently been characterized as a 40-kDa protein probably anchored to the cell surface by glycosyl-phosphatidylinositol. Using immunoperoxidase histochemical methods, we examined 37 squamous-cell carcinoma (SqCC) samples from cervix, lung, esophagus and other origins, and 12 normal squamous epithelia of the cervix and esophagus for their reactivity with MAb K1. Of the SqCC specimens, 81% showed K1 reactivity with variable intensity, but none of 12 normal tissue samples of squamous epithelia did so. Two patterns of CAK1 expression in tumor samples were found, i.e., a heterogeneous pattern with strong intensity, and a homogeneous pattern with weak intensity. Three carcinomas in situ of the larynx, vulva and esophagus were moderately positive with K1, suggesting that CAK1 antigen may occur in the early stage of carcinogenesis of SqCC. The expression of CAK1 was also compared with expression of CA125, HER-2/neu, p53 and P-glycoprotein, and MAb K1 was found to react most consistently with SqCC. Since K1 reacts with a majority of cervical and esophageal carcinomas but has no detectable reactivity in normal epithelia of the cervix uteri and esophagus, MAb K1 could be of value as a reagent to help distinguish between normal and neoplastic cells on sections as well as in cytological samples.

1-Butanol↗