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Biomedical subjects

C C Yang

Publications and source records attributed to C C Yang.

At least 163 records · Page 9Linked to original sources

Overexpression of protein kinase FA/GSK-3 alpha (a proline-directed protein kinase) correlates with human hepatoma dedifferentiation/progression.

Computer analysis of protein phosphorylation sites sequence revealed that transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of the proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of protein kinase FA/glycogen synthase kinase-3 alpha (kinase F(A)/GSK-3 alpha) (a member of PDPK family) has been optimized for human hepatoma and used to demonstrate for the first time significantly increased (P < 0.01) activity in poorly differentiated SK-Hep-1 hepatoma (24.2 +/- 2.8 units/mg) and moderately differentiated Mahlavu hepatoma (14.5 +/- 2.2 units/mg) when compared to well differentiated Hep 3B hepatoma (8.0 +/- 2.4 units/mg). Immunoblotting analysis revealed that increased activity of kinase FA/GSK-3 alpha is due to overexpression of the protein. Elevated kinase FA/GSK-3 alpha expression in human hepatoma biopsies relative to normal liver tissue was found to be even more profound. This kinase appeared to be fivefold overexpressed in well differentiated hepatoma and 13-fold overexpressed in poorly differentiated hepatoma when compared to normal liver tissue. Taken together, the results provide initial evidence that overexpression of kinase FA/GSK-3 alpha is involved in human hepatoma dedifferentiation/progression. Since kinase FA/GSK-3 alpha is a PDPK, the results further support a potential role of this kinase in human liver tumorigenesis, especially in its dedifferentiation/progression.

Calcium-Calmodulin-Dependent Protein Kinases↗

Morin hydrate inhibits azo-initiator induced oxidation of human low density lipoprotein.

We demonstrated that the flavonoid morin hydrate at 75-100 microM protects against the oxidation of low density lipoprotein (LDL) by free radicals produced by 2,2'-azo-bis(2-amidinopropane) dihydrochloride. Morin hydrate reduces the relative electrophoretic mobility, malondialdehyde equivalents and lipid peroxide level of oxidized LDL. On the other hand, Trolox (an analogue of vitamin E) showed less protective effect in the present system. Since free radical mediated oxidation of LDL is implicated to be a cause of atherogenesis, morin hydrate may be a candidate chemotherapeutic agent herein.

Amidines↗

The early evaluation of induced osteoarthritis in rats with 99Tcm-pertechnetate scans.

Osteoarthritis was induced in 30 adult rats by serial injection of papain (3.5 mg kg-1) into the right knee on days 1, 4 and 7 of the study, with equal volumes of normal saline being injected into the left knee as a control. The severity of the induced arthritis was observed after the subcutaneous injection of 37 MBq kg-1 (1 mCi kg-1) 99Tcm-pertechnetate in the neck 24 h and 1, 2, 4, 6 and 8 weeks after the first intra-articular injection of papain. The ratio of radioactivity in the right compared with the left knee of each rat was measured as an index of the severity of osteoarthritis. After the scans, X-rays of both knees were obtained. At each state of progression, a rat was sacrificed and bilateral knee sections were performed for further pathological evaluation. The results were then compared with the changes in the radioactivity ratio and the X-rays. The radioactivity ratio of the knees reached a peak approximately 25 min after the subcutaneous injection of 99Tcm-pertechnetate and this value was chosen as the index of the severity of osteoarthritis. Marked differences in radioactivity in the left and right knees were observed as early as 24 h after the first intra-articular injection of papain. The radioactivity ratio increased with time, which correlated well with pathological changes. Joint space narrowing was not found on X-ray until 4 weeks post-injection. The results showed that the 99Tcm-pertechnetate scans correlated well with the pathological changes and that this method can detect osteoarthritis earlier than joint X-rays. It is suggested that a 99Tcm-pertechnetate scan is a useful means of evaluating early changes in induced osteoarthritis in rats.

Animals↗

Auto- and cross-spectral analysis of cardiovascular fluctuations during pentobarbital anesthesia in the rat.

We applied auto- and cross-spectral analysis of systemic arterial pressure (SAP) and heart rate (HR) signals to quantify the effects of pentobarbital sodium on short-term cardiovascular fluctuations in adult, male Sprague-Dawley rats. Intravenous administration of pentobarbital, delivered as a bolus injection (5, 10, or 20 mg/kg) or continuous infusion (10, 20, or 40 mg.kg-1.h-1), elicited only mild hypotension and tachycardia. This was accompanied by a dose-related depression of the very low (0-0.25 Hz) and low (0.25-0.8 Hz)-frequency components of both SAP and HR signals and high (0.8-2.4 Hz)-frequency component of HR signals. Cross-spectral analysis of SAP and HR signals during intravenous infusion of pentobarbital revealed a maintained coherence in the high-frequency range, together with a gradual and dose-related decrease in magnitude of transfer function and baro-receptor reflex sensitivity. Stable plasma concentration and all hemodynamic parameters were observed during 120 min of infusion at 20 mg.kg-1.h-1. Under this dosing condition, autonomic blockade by phentolamine, propranolol, or atropine still evoked discernible but differential reductions in the SAP and HR spectral components. Our data suggest that continuous intravenous administration of pentobarbital at 20 mg.kg-1.h-1 offers maintained anesthesia while preserving the capacity of cardiovascular regulation.

Anesthesia↗

Transfer function analysis of ventilatory influence on systemic arterial pressure in the rat.

We evaluated the hypothesis that fluctuations in systemic arterial pressure (SAP) are under the influence of the respiratory pumping mechanism subjected to a modulatory action by the autonomic nervous system that is exerted primarily on the heart. Computer-generated broad-band mechanical ventilation (0-3 Hz) was applied to Sprague-Dawley rats that were anesthetized with ketamine and paralyzed with pancuronium. We observed excellent coherence between lung volume and SAP signals at ventilatory rates between 0.5 and 2.5 Hz; this coherence was unaffected by phentolamine, propranolol, atropine, bilateral vagotomy, or ventilatory stroke volume at 2-4 ml. Whereas bilateral vagotomy exerted no discernible effect, propranolol elicited a significant frequency-dependent (0.5-1.5 Hz) reduction in the magnitude of lung volume-SAP and lung volume-pulse pressure transfer functions. There was also a shift toward 0 degree for the phase of the lung volume-SAP transfer function over the same frequency range. We conclude that the high-frequency component (0.8-2.4 Hz) of the SAP spectrum may be generated by the respiratory pumping mechanism. However, the lower-frequency end of this mechanical influence is subjected to additional amplification by the autonomic nervous system, in which the beta-adrenergic system played a major role via its influence on the heart.

Adrenergic beta-Antagonists↗

Effects of intraperitoneal antibiotics on human peritoneal mesothelial cell growth.

Peritonitis is one of the most frequent complications of continuous ambulatory peritoneal dialysis (CAPD). Necrosis and exfoliation of the mesothelial cell layer of the peritoneum develop during the acute phase of peritonitis. Agents that hamper regeneration of mesothelial cells will cause delayed recovery of the peritoneal surface, which results in continuous exposure of underlying stem cells to the stimulation of growth factors and possibly leads to peritoneal fibrosis syndrome. The aim of the present study is to determine the effects of several intraperitoneal antibiotics on human peritoneal mesothelial cell (HPMC) growth at their usual loading and maintenance doses. HPMCs were isolated from human omenta. Proliferation of HPMC was evaluated by modified methyltetrazolium assay and cell membrane integrity was assessed by lactate dehydrogenase method. The results showed that most cephalosporins exert an inhibitory, even toxic, effect on HPMCs at their loading doses. Cephalothin, cephradine, cefamandole, cefoxitin, cefuroxime and cefoperazone inhibited HPMC proliferation at their maintenance doses. Vancomycin, clindamycin, aztreonam, piperacillin, imipenem, tobramycin and ceftriaxone have no effect in their usual intraperitoneal doses. From the viewpoint of peritoneal protection, not only drug sensitivity of the causative microorganisms but also effects of antibiotics on HPMC regeneration should be considered when selecting antibiotics for CAPD peritonitis.

Anti-Bacterial Agents↗

Sequence of the 5'-flanking and 5'-UTR regions of the rat endothelin-A receptor gene.

Endothelin receptors bind peptides of the endothelin family, the most potent vasoconstrictors known, and have been implicated in hypertension. To begin to define DNA sequences necessary for the transcriptional regulation of the rat endothelin type A receptor (ETA), we have sequenced the 5'-untranslated region (UTR) and part of the 5'-flanking region, a total of 1153 nucleotides. Comparison of the rat and human sequences revealed a 57% similarity in the 5'-flanking sequences, and a 63% similarity in the 5'-UTRs. Several conserved sequences were identified, including GATA and E-boxes, which may be important for the regulation of ETA gene expression. Primer extension analysis identified two transcription initiation sites within the rat gene.

Animals↗

Acute pancreatitis following organophosphate intoxication.

BACKGROUND: Acute pancreatitis as a complication of organophosphate intoxication has been infrequently addressed. Previous reports have suggested that acute pancreatitis may follow the oral ingestion of several organophosphates, including parathion, malathion, difonate, coumaphos, and diazinon, or after cutaneous exposure to dimethoate. No cases of acute pancreatitis following mevinphos (CAS 7786-34-71) poisoning have been reported to date. The possible pathogeneses of the pancreatic insult in organophosphate intoxication are excessive cholinergic stimulation of the pancreas and ductular hypertension. CASE REPORT: We describe a patient presenting with painless acute pancreatitis following an intentional ingestion of large amounts of mevinphos. Serum amylase and lipase values were increased and determination of amylase isoenzymes confirmed a pancreatic origin. A computerized tomograph of the abdomen showed diffuse swelling of the pancreas. The patient was discharged after a seven week clinical course, complicated by a delayed neuropathy. CONCLUSIONS: As acute pancreatitis in organophosphate intoxication may be more common than reported, serum pancreatic enzymes and appropriate imaging studies should be more liberally utilized. Early recognition and appropriate therapy for acute pancreatitis may lead to an improved prognosis.

Acute Disease↗

Taiwan National Poison Center: epidemiologic data 1985-1993.

UNLABELLED: The Taiwan National Poison Center has received more than 30,000 telephone calls since its establishment in July 1985. OBJECTIVE: To obtain more information about poisoning exposures in Taiwan, a retrospective analysis was conducted of all telephone calls to the center concerning human poisoning exposures July 1985 through December 1993. METHODS: The following data were tabulated: age, sex, intent of exposure, route of exposure, substances ingested and clinical severity. RESULTS: During the eight years (1985-1993), 23,436 telephone calls concerning human poisoning exposure were recorded. Adults accounted for most cases (75.2%) and exposures involving males (54.2%) were somewhat more prevalent than female poisoning exposures (44.7%). Intentional poisonings (54.6%) were more common than unintentional poisonings (40.1%), with an inverse relationship in pediatric poisoning exposures. After amphetamines, the most frequently ingested poisons were pesticides, benzodiazepines, and cleaning products. Fatalities occurred most frequently following ingestion of pesticides. The mortality rate was 5.7% for all exposures. CONCLUSIONS: Human poisoning is a serious problem in Taiwan. The reduction of suicide attempts is a major objective. Childhood poisonings are underreported and of high mortality.

Adolescent↗

Acute isoniazid intoxication: a case report.

Since its introduction in 1952, isoniazid has remained one of the drugs of choice in the treatment and prophylaxis of tuberculosis. In populations with a high prevalence rate of tuberculosis or suicide rate, acute ingestion of isoniazid has occasionally been reported. Acute intoxication by isoniazid is known to cause symptoms of seizures, metabolic acidosis, coma, and even death. These clinical symptoms, however, are not well recognized by physicians in Taiwan, even though the prevalence rate of tuberculosis is relatively high here. This report concerns the case of a 25-year-old female with a past history of tuberculosis who presented with the symptoms of refractory seizures, metabolic acidosis and deep coma after intentional ingestion of some unknown drug. Although implicating agents were not recognized initially, she was successfully revived with basic resuscitation, anticonvulsants and correction of metabolic acidosis. A review of her history revealed that her ingestion of five grams of isoniazid in this case was responsible for the entire clinical spectrum. Given easy access to isoniazid in Taiwan, a diagnosis of isoniazid poisoning should always be considered in patients who present with the classical symptoms of refractory seizures, metabolic acidosis and coma.

Acidosis↗

Clinical experience in poisonings following exposure to blasticidin S, a curiously strong fungicide.

The fungicide blasticidin S has been used against a rice blast disease. Reports on its human toxicity are extremely limited, and irritation to GI tract, eye and skin are the presenting symptoms in most afflicted cases. Fatalities resulting from profuse intestinal fluid loss with subsequent hypotension have also been recorded. In an attempt to delineate the clinical pictures of blasticidin S poisoning, a retrospective study covering an 8.5-y period was then conducted. A total of 28 blasticidin S poisoning exposures, including 24 suicidal ingestions, were recorded. The ingested amounts in most cases were rather large, while 2 cases were found with estimated dosages up to 10 g. The presented symptoms in most cases were immediate vomiting, abdominal pain, diarrhea and sore throat which were resolved after conservative treatment. Nevertheless, hypotension, arrhythmia, acrocyanosis, aspiration, and even coma occurred in severe cases. Fatalities were noted in 5 patients, in whom profound hypotension and severe aspiration pneumonitis were the main features. Poisoning following blasticidin S ingestion remains a challenge to acute health care physicians. Adequate administration of i.v. fluid and careful monitoring of electrolytes have been considered as the mainstay in the treatment of blasticidin S poisoning. Prevention of aspiration and ventilatory support are also crucial for life-saving since poisoning cases might succumb after massive aspiration.

Aged↗

[Study on technetium-99m in radiopharmaceuticals].

The technetium field involving a new element of which chemistry has not been honed in the research during the century is particularly challenging, it is exciting and satisfying to see the successful development of a radiopharmaceutical agent which gives the clinical doctor new tools with which to assess function and in vivo biochemistry in nuclear medicine. The clinical application of technetium in nuclear medicine will parallel with the development of technetium chemistry in organic-, analytical-, medical- and biochemistry, and it is likely that useful new Tc-99m radiopharmaceuticals will rapidly make world-wide progress in the future years. The design and synthetic modifications of ligand structure in organic chemistry will impart new biological properties to the technetium complexes. A structure characterization Tc-99m labelled radiopharmaceuticals is highly desirable in analytical chemistry. We take much interest in the structural characterization of Tc-99m complexes stems to establish a structure/in vivo activity relationship in medical chemistry. The current clinical trend is to use Tc-99 radiopharmaceuticals with Tc-99m "carrier-added" experiments for studies of chemical structure and biochemical mechanism of action. Technical difficulties in the various labeling approaches to these bifunctional chelating agents (BCA) which seem promising are often encountered during the ached procedures. High priority is given to development of Tc-99 m radiopharmaceuticals for studies of substrate utilization and localization of specific biological recognition sites. New accomplishments in technetium radiopharmaceutical are likely to be reported in the near future.

Humans↗

[The study on the in-vitro stability of Tc(V)-99m dimercaptosuccinic acid].

Tc(V)-99m DMS, developed by Yokoyama et al. in 1981, has been recognized to be advantageous for the scintigraphic diagnosis of various malignant tumors and their metastasis, the aim of this study is to assess the in-vitro stability of Tc(V)-99m DMS. Thin-layer chromatography, including paper chromatography and silica gel thin layer chromatography, is performed to determine the change of radiochemical species presented in the reconstituted solution of Tc(V)-99m DMS prepared from the DMS kit (Institute of Nuclear Energy Research, Atomic Energy Council R.O.C.) and the commercial DMSA kit (Nephroscint, IRE CELLTARG Radiopharmaceuticals Japan). The bioscan imaging scanner is used to measure the Rf value and labeling efficiency of radiochemical species on the chromatographic strip. The in-vitro stability of Tc(V)-99m DMS prepared from the DMS kit and the commercial DMSA kit is studied by examining various parameters which include temperature(degree C) and time(hr) after reconstitution. The results show that the in-vitro stability of Tc(V)-99m DMS prepared from the DMS kit is actually better than that from the commercial DMSA kit. The one-step labeling method of DMS kit is much simpler than the two-step labeling method of DMSA kit.

Drug Stability↗

Tetrodotoxin poisoning in Taiwan: an analysis of poison center data.

Tetrodotoxin (TTX) poisonings are not infrequently seen in Taiwan, and several outbreaks have been recorded by the Poison Control Center (PCC)-Taiwan during 1988-1995. However, their demographic data, clinical features, and medical outcome have not been reported. A retrospective study analyzed the PCC data of TTX poisonings. All patients reported to the PCC-Taiwan as TTX poisoning from July 1988 through December 1995 were included. Excluding 2 incidents, the diagnosis of TTX poisoning was documented by identification of puffer fish and/or by the analysis of TTX in it. Patient age, sex, season of poisoning, substances ingested, incubation period, presenting symptoms, recovery time, and clinical outcome were analyzed. A total of 20 incidents involved 52 patients. Males outnumbered females (52% vs 41%) with sex undetermined in 4 patients. Most incidents occurred in the spawning seasons of puffer fish, eg March to May. Puffer fish ingestion accounted for 18 incidents; ingestion of gastropod mollusks and Gobius criniger were responsible for the other 2 incidents. Following ingestion of puffer fish and other poisonous marine animals, most symptoms developed within 6 h with complete recovery usually in 24 h. Symptoms of TTX poisoning were similar as those previously reported; however, unusual features, such as hypertension (24%), pinpoint pupils (4%), bronchorrhea and facial flush (2%), were also seen. The mortality rate was 13.5%. The violent neurotoxin is present in puffer fish and occurs in other marine animals. Without adequate therapy, patients may have serious morbidity or even succumb. Careful identification of puffer fish and other poisonous marine animals, as well as proper treatment of TTX poisoning patients, are mandatory to successfully handle cases of TTX poisoning.

Aging↗

Adverse drug reactions in a medical ward.

The preliminary results of an interdisciplinary active surveillance adverse drug reaction (ADR) reporting program conducted from April 1992 to December 1993 in the family medicine ward of National Taiwan University Hospital are presented. During this period, every admitted patient was screened for any possible drug-related problems; suspected ADRs were evaluated and documented. The USA Food and Drug Administration's definition of ADR was used, and Naranjo's scale was used to estimate the probability of drug-induced events. A total of 41 ADRs were identified in 38 patients. Among these 41 cases, 18 ADRs occurred during hospitalization, and 23 were the reason for hospitalization. The incidence of ADRs rated as probable or highly probable during hospital stay was 2.0%, or 2.7% if possible reactions were included (based upon 666 hospital admissions to the unit during the study period). The occurrence of admissions due to ADRs rated as highly probable or probable was 2.7%, or 3.5% if possible reactions were included. Twenty-one ADRs (51.2%) were type A reactions and 20 (48.8%) were type B. Thirty-three ADRs (80.5%) were classified as serious or moderate. There was no mortality. Further studies are warranted to determine the incidence of ADRs in different patient populations in Taiwan.

Adult↗

Rapid inhibition of protein histidine phosphorylation by UV-irradiation in Xanthomonas oryzae pv. oryzae.

Exposure of Xanthomonas oryzae pv. oryzae cells to 254 nm UV radiation resulted in an alteration of protein phosphorylation. Labelling of the phosphohistidine-containing proteins with molecular masses of 81 and 32 kDa, named p81 and p32, was rapidly reduced following UV irradiation in the early exponential cells, but the decrease was not detected in mid-exponential cells. Mitomycin C, a DNA replication inhibitor, and rifampicin, a drug generally used to inhibit RNA synthesis and DNA replication, were also found to reduce the histidyl phosphorylation. However, this alteration of protein phosphorylation was not hindered by chloramphenicol treatment. A possible role for these histidyl phosphoproteins in sensing UV light is proposed.

Bacterial Proteins↗

The primary structure of Hyphomicrobium X dimethylamine dehydrogenase. Relationship to trimethylamine dehydrogenase and implications for substrate recognition.

The gene encoding dimethylamine dehydrogenase from Hyphomicrobium X has been cloned and over-expressed in Escherichia coli. Using the chemically determined protein sequence, primers were designed to amplify DNA fragments encoding the proximal and distal parts of the gene. These fragments were used to synthesise two probes and the dmd gene was cloned as part of two BamHI fragments isolated from digested genomic DNA. The sequence of the complete open reading frame was determined on both strands and contained 2211 bp coding for a protein of 736 amino acids, including the N-terminal methionine residue that is removed when expressed in the native host. The molecular mass of the processed apoprotein predicted from the DNA sequence is 82,523 Da. Dimethylamine dehydrogenase is closely related to the trimethylamine dehydrogenase of Methylophilus methylotrophus W3A1 (63.5% identical) and other class I FMN-binding beta 8 alpha 8 barrel flavoproteins. Residues in the active site of trimethylamine dehydrogenase that are known, or implicated, to be important in catalysis are conserved in dimethylamine dehydrogenase. Sequence alignment of dimethylamine and trimethylamine dehydrogenases suggests that the specificity for secondary and tertiary amines resides in a single amino acid substitution in a substrate-binding aromatic bowl located in the active site of the enzymes.

Amino Acid Sequence↗