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D Wu

Publications and source records attributed to D Wu.

At least 523 records · Page 29Linked to original sources

Presence of functionally active cytochrome P-450IIE1 in the plasma membrane of rat hepatocytes.

Recent experiments have described the presence of cytochrome P-450 and certain P-450 isozymes in the plasma membrane of rat liver. Experiments were carried out to evaluate whether cytochrome P-450IIE1 was present in the plasma membrane fraction of livers from control rats and rats treated with 4-methylpyrazole, which induces this isozyme. Using immunofluorescence, fluorescence was detected at the surface of intact hepatocytes that were initially incubated with anti-P-450IIE1 IgG, but not preimmune IgG, followed by incubating with goat antirabbit IgG conjugated with either fluorescein or rhodamine. The fluorescence appeared to be uniformly distributed across the entire surface. Intense intracellular staining could be observed when the hepatocytes were permeabilized by acetone treatment. Similar results were obtained with control hepatocytes; however, the fluorescence intensity was considerably less than that shown by the induced hepatocytes. Hepatocytes isolated from the pericentral zone of the liver acinus displayed more intense fluorescence at the surface than did hepatocytes from the periportal zone. Purified plasma membranes oxidized dimethylnitrosamine to formaldehyde at rates that were 14% to 30% that of the microsomes, which exceeds the 3% contamination of the plasma membranes by microsomes as assessed by glucose-6-phosphatase activity. Immunoblots of the plasma membranes revealed the presence of a single band, whose intensity of staining was 14% to 26% that of the microsomes. Oxidation of dimethylnitrosamine and immunoblot intensity were about twofold greater with plasma membrane fractions from 4-methylpyrazole-treated rats than controls. These results suggest the presence of inducible, functionally active P-450IIE1 in the plasma membrane, which may be of toxicological significance in view of the preferential metabolism of a variety of hepatotoxins and carcinogens and the elevated production of reactive oxygen intermediates by this isozyme.

Animals↗

Nature of dual atrioventricular node pathways and the tachycardia circuit as defined by radiofrequency ablation technique.

OBJECTIVES: A comprehensive electrophysiologic study followed by selective radiofrequency ablation from three sites was performed in patients with atrioventricular (AV) node reentrant tachycardia to better delineate the nature of the tachycardia circuit. BACKGROUND: We postulated that the retrograde fast pathway is the anterior superficial group of transitional cells and the slow pathway is the compact node with its posterior input of transitional cells. Twenty-three consecutive patients were studied. In nine, the atria could be dissociated from the tachycardia by delivery of an atrial extrastimulus during tachycardia. METHODS: Radiofrequency ablation was performed with three approaches. The anterior approach was designed to interrupt the anterior superficial atrial input to the compact node, the posterior approach to interrupt the posterior atrial input to the compact node and the inferior approach to destroy the compact node itself. RESULTS: Selective ablation of the retrograde fast pathway was achieved in seven patients, six with the anterior and one with the inferior approach. Anterograde fast pathway conduction was not affected, whereas retrograde fast pathway conduction was either abolished or markedly depressed. None had induction of echoes or tachycardia after ablation. Selective ablation of the slow pathway was successful in 13 patients, 1 with anterior, 3 with posterior and 9 with inferior approaches. In these 13 patients, both anterograde and retrograde fast pathway conduction were not affected, the dual pathway physiology was abolished and the tachycardia was not inducible after ablation. Ablation of both the retrograde fast pathway and the slow pathway occurred with the inferior approach in three patients. CONCLUSIONS: We conclude that the retrograde fast pathway is likely to be the anterior superficial group of transitional cells, whereas the slow pathway is the compact node and its posterior input of transitional cells. A barrier seems to exist between the atrium and the tachycardia circuit. In a broad view of the AV node structure, the tachycardia circuit is confined to the node.

Atrial Function↗

Effect of 60Co gamma-irradiation on the nonspecific cytotoxicity of alveolar macrophages in vitro.

This paper reports on the effect of radiation on the nonspecific cytotoxicity of rat alveolar macrophages (AM). AM (effector cells) of bacille Calmette-Guerin-activated Wistar rats were irradiated with 60Co gamma rays in vitro to give doses of 0, 100, 300, and 500 Gy. Three hours after irradiation, the AM were cultured with human lung adenocarcinoma AGZY83-a and HeLa target cells in 125I-deoxyuridine-containing media for 6 hr and the cytotoxicity indexes determined. The results indicated that the cytotoxicity indexes of AM against human lung adenocarcinoma cells and HeLa cells were 94.3 +/- 0.3% and 81.3 +/- 1.9%, respectively. The cytotoxicity indexes using an effector/target cell ratio (E/T) of 10 seemed to be greater than with ratios of 20 and 30. The cytotoxicity indexes of AM (7 rats), irradiated to give doses of 0, 100, 300, and 500 Gy, against adenocarcinoma cells at an E/T ratio of 10 were 87.9 +/- 8.4%, 65.4 +/- 14.1%, 47.5 +/- 17.5%, and 36.7 +/- 9.7%, respectively. The significance of the nonspecific cytotoxicity of AM in the immunological elimination of tumors and the inhibitory effect of radiation on AM cytotoxicity are discussed.

Adenocarcinoma↗

Erythrocyte sodium-lithium countertransport in Chinese: its relationship to family history of hypertension.

Rates of sodium (Na+)-stimulated lithium (Li+) efflux (Na(+)-Li+ countertransport) and ouabain-sensitive Na+ efflux (Na+ pump) were determined in erythrocytes of Chinese normotensive and hypertensive subjects. Near-maximal rate of Na(+)-Li+ countertransport was found to be significantly higher in hypertensive than normotensive subjects. No significant difference was observed for the rate of Na+ pump between them. A second series of study involved normotensive subjects without and with hypertensive parent(s) (group A and B, respectively) and hypertensive subjects (group C). We found that the rate of Na(+)-Li+ countertransport in group A was significantly lower than that of group B and C, while no difference existed between group B and C. No significant difference was observed for the rate of Na+ pump among the three groups. Our results suggested that Na(+)-Li+ countertransport activity could be a genetic marker for essential hypertension in Chinese, similar to that as proposed in Caucasians.

Adult↗

[DNA repair capacity measurement and possibility of heterozygote detection using nucleoid sedimentation technique among members taken from 3 xeroderma pigmentosum (XP) families].

The nucleoid sedimentation test was used to analyse the DNA repair capacity in 35 members taken from 3 xeroderma pigmentosum (XP) families after their peripheral blood lymphocytes being exposed to UV irradiation or N-methyl-N-nitro-N-nitrosoguanidine (MNNG) at a dose of 2.5 microJ/mm2 and 2 micrograms/ml respectively. The results showed that the 6 XP patients all failed to repair their damaged DNA even after 20-hour incubation at 37 degrees C. The repair ratios were 0.61 +/- 0.13 for UV and 0.44 +/- 0.15 for MNNG while those of non-related normal members usually reached 0.96 +/- 0.07 and 0.71 +/- 0.07 for both UV and MNNG after 11-hour incubation. It is interesting to note that 9 obligatory heterozygotes (parents and grandparents of XP patients) and 4 highly possible heterozygotes (blood relatives of XP patients) also showed very poor DNA repair capacity: they could not accomplish their repair process even after 20-hour incubation. It has been showed that the nucleoid sedimentation test can probably be used to pick out the heterozygotes in XP families.

Adolescent↗

Modulation of renal epithelial cell growth by glucosylceramide. Association with protein kinase C, sphingosine, and diacylglycerol.

Two independent approaches were employed to explore the potential role of endogenous glucosylceramide or a closely related glucosphingolipid in mediating the cellular proliferation of Madin-Darby canine kidney cells. First, cultured cells were depleted of glucosphingolipids by exposure to a glucosylceramide synthase inhibitor, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol. This agent markedly inhibited cell growth and DNA synthesis in a time- and concentration-dependent manner. Second, cells were grown in the presence of conduritol B epoxide, an inhibitor of glucosylceramide beta-D-glucosidase. Exposure of cells to this inhibitor resulted in the time-dependent accumulation of glucosylceramide with a corresponding increase in cellular proliferation. Alterations in protein kinase C activity were evaluated as a potential mechanism for these effects on growth. Both membrane- and cytosol-associated protein kinase C (PKC) activity declined under conditions of glucosylceramide synthase inhibition and increased under conditions of beta-glucosidase inhibition. The changes in PKC activity were evident after DEAE-cellulose purification. Diacylglycerol levels increased in response to both glucosylceramide synthase and beta-glucosidase inhibition. Ceramide and sphingosine levels changed only in the presence of D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, increasing due to lack of conversion to glucosylceramide. However, the elevation in endogenous sphingosine was probably insufficient to account for the decrease in PKC, considering the high level of diacylglycerol in the cells. These data demonstrate an association between glucosylceramide levels, PKC activity, and cell growth.

Animals↗

Sequence of an operon containing a novel delta-endotoxin gene from Bacillus thuringiensis.

An insect larval toxin designated CryII is produced by several subspecies of Bacillus thuringiensis and differs from the other major delta-endotoxins in these bacteria in its size, toxicity profile and presence as part of an operon with three open reading frames (ORF). Such an operon from a novel B. thuringiensis isolate has been cloned and differs from one previously characterized in the following ways: (a) the size and number of amino acid repeats in one of the ORFs; (b) the smaller size of the CryII protoxin and the presence of a unique 110-kDa CryII-related antigen; and (c) high larvicidal activity for a particular Lepidopteran but low activity for a Dipteran. Various subclones of this operon were introduced into a plasmid-free B. thuringiensis strain and only the cryII gene was found to be necessary for protoxin accumulation.

Amino Acid Sequence↗

Repetitive sinoatrial exit block as the major mechanism of drug-provoked long sinus or atrial pause.

Prolonged sinus or atrial pause occurred in six patients with paroxysmal supraventricular tachycardia after drug administration. All six patients had normal sinus node function during control electrophysiologic study; the sinus cycle length ranged from 510 to 900 ms (mean 743 +/- 141) and the longest sinus node recovery time ranged from 800 to 1,230 ms (mean 1,018 +/- 168). A long sinus or atrial pause occurring at the termination of tachycardia or cessation of atrial pacing, ranging from 3,100 to 8,200 ms (mean 6,270 +/- 1,674), was provoked by the administration of various drugs. These included an intravenous bolus injection of adenosine triphosphate (5 mg; one patient), intravenous bolus injection of verapamil (5 mg; one patient), a combination of a single oral dose of diltiazem (120 mg) and propranolol (20 to 40 mg; three patients), oral diltiazem (240 mg/day; one patient) and a combination of oral diltiazem (240 mg/day) and propranolol (160 mg/day; one patient). In five patients, low frequency deflections suggestive of sinus node activity with a cycle length between 620 and 3,500 ms were recorded during pauses. These findings suggest that repetitive sinoatrial exit block was responsible for the pause. Sinus slowing with a long arrest suggesting suppression of sinus automaticity was also noted in three of these five patients; the longest sinus arrest in these three patients was 4,160, 4,800 and greater than 4,910 ms, respectively. The remaining patient with a pause of 6,840 ms had no recordable sinus activity, either reflecting suppression of sinus automaticity or technical failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Case-control study of cigarette smoking and primary hepatoma in an aflatoxin-endemic region of China: a protective effect.

Aflatoxin is believed to be a major causative agent in the high incidence of primary liver cancer seen in certain regions of the world. In Fujian Province, an aflatoxin-endemic region of China, we compared the cigarette smoking habits of 200 primary hepatoma patients with those of 200 matched nonhepatoma controls. We excluded from our study all individuals with evidence of hepatitis B virus serum antigen and/or alcoholic cirrhosis. Interestingly, two groups of hepatoma patients could be discerned. In patients more than 50 years of age, a significantly higher number of cases of primary hepatoma was found among nonsmokers than smokers (odds ratio = 2.06; 95% confidence interval = 1.32-3.20). In patients less than 50 years of age, this difference was not seen. Previous studies in the rat, mouse and duck had suggested that agents present in cigarette smoke might induce a cytochrome P450-mediated detoxication pathway, leading to protection against aflatoxin-induced primary liver cancer. Our clinical data in the present study are therefore consistent with the previous laboratory animal experiments.

Adult↗

[The structure and absolute configuration of isorupestonic acid from Artemisia rupestris L].

A new sesquiterpene compound named isorupestonic acid was isolated from Artemisia rupestris and its absolute stereostructure was elucidated as 3B by spectral and X-ray crystallographic methods. Interestingly, the isorupestonic acid is based upon an unusual 6, 7 membered ring skeleton differing from the 5, 7 membered ring rupestonic acid although both have the same absolute configuration at C-1. The biogenesis of isorupestonic acid most likely involves breaking the C4-C5 bond of rupestonic skeleton and forming the C5-C14 bond. The absolute configuration of rupestonic acid was also determined as 4C by X-ray analysis and CD data.

Azulenes↗

Chemical influences on the specificity of tyrosine phosphorylation.

Biological tyrosine phosphorylation has become an extensively studied reaction. Little, however, is known of the chemistry involved. The acetylation of the tyrosyl phenolic hydroxyl group by N-acetylimidazole was studied as a model acylation reaction over the pH range 7.5-9.5. The reactivities of tyrosine and 3-fluorotyrosine were compared. The ratio of reactivities, kappa F-Tyr/kappa Tyr, decreases with increasing pH. Extrapolation to the state in which equivalent concentrations of the two derivatives exist indicates that, consistent with Brønsted theory, tyrosine is 17 times more reactive than fluorotyrosine. No reactivity was observed with tetrafluorotyrosine, 3-nitrotyrosine, or 3,5-dinitrotyrosine. A peptide containing fluorotyrosine was synthesized and compared with the tyrosine-containing peptide as a substrate for the insulin receptor/tyrosine kinase. In both the presence and absence of insulin, the tyrosine peptide was phosphorylated with higher Vm and Km values than the fluorotyrosine peptide was. These results suggest that ionization of the tyrosyl hydroxyl group has an effect on both the chemical and enzymatic reactivities of the tyrosyl residue in acylation reactions. A model is suggested in which deprotonation of the acceptor occurs upon binding of the substrate to the kinase and implicates a role for the substrate site microenvironment in defining substrate specificity.

Amino Acid Sequence↗

Surgical cure of automatic atrial tachycardia by partial left atrial isolation.

Partial left atrial isolation was performed in a 16-year-old girl with persistent atrial tachycardia refractory to antiarrhythmic agents for 3 years. Intraoperative atrial epicardial and endocardial mapping showed that the earliest atrial activation occurred in an area lateral to the junction of the right superior pulmonary vein and the left atrium. An incision isolating the right half of the left atrial body containing the area of the earliest atrial activation and both right pulmonary veins from the remainder of the left atrium was made. The incision was then reapproximated. An excision encircling the interatrial septum containing the upper anterior portion of the septum with early activation was also made, and the atrial septal defect was repaired with a pericardial patch. The patient has been in sinus rhythm and free of arrhythmia for a follow-up period of 12 months.

Adolescent↗

Formation of cyclic imide-like structures upon the treatment of calmodulin and a calmodulin peptide with heat.

Protein cyclic imide is the putative intermediate in the formation of sites of carboxyl-methylation in eukaryotic proteins. Conditions known to induce the formation of a cyclic imide in model peptides have been applied to a protein, calmodulin. Heating of calmodulin in the dry state at 100 degrees C for 24 h after lyophilization from a pH 2.0 or pH 6.0 solution produces derivatives with altered chromatographic properties in anion-exchange HPLC. At pH 6.0, complete activity of calmodulin was retained. Analysis with Fourier transform infrared (FTIR)-photoacoustic spectroscopy demonstrated the presence of a new structure in the calmodulin molecule consistent with modification of carboxylic acid groups. The conversion of calmodulin is dependent upon the absence of Ca2+ (the presence of 1 mM ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid). A peptide analogous to the calcium binding regions of calmodulin, Asp-Lys-Asp-Gly-Asn-Gly-Thr-Ile-Thr-Thr-Lys-Glu, is also converted, upon heating, to chromatographically different forms in reversed-phase chromatography. This process is also dependent upon the absence of calcium. Sequence analysis of the peptide derivatives reveals a second amino terminus, implicating peptide bond hydrolysis in the product. A dipeptide, Asp-Gly, known to form a cyclic imide structure under similar conditions is also hydrolyzed during sequence analysis consistent with cleavage occurring at the position of the cyclic imide structure. Asp3 is suggested to be the site of cyclic imide formation in the calmodulin peptide. The presence of a cyclic imide structure is also confirmed by the application of FTIR-photoacoustic spectroscopy. These data suggest that cyclic imide formation in calmodulin has been induced, possibly at one, or more, of the calcium binding loops of the protein. These modification reactions may provide a basis for future investigations of cyclic imide formation in proteins.

Amino Acid Sequence↗

A reappraisal of appendicitis in the elderly.

Historically, appendicitis in the elderly is associated with higher morbidity and mortality. Ninety-six patients over 60 years of age with appendicitis treated over a 10-year period were reviewed. Only 20% presented classically with anorexia, fever, right lower quadrant pain, and an elevated white blood cell count. One third of the patients had greater than 48 hours delay to admission. Objective diagnostic testing was often confusing and unreliable. At the time of admission, only 51% were diagnosed as having possible appendicitis. Eighty-three percent of our patients underwent surgery within 24 hours, and 72% had frank perforation. Thirty-two percent of those surviving developed complications, and 83% of these patients had perforated appendicitis. Complications were twice as likely in patients with perforation. Despite the relatively high morbidity, there were only four deaths in patients with coexistent carcinoma. Because of the later and atypical presentation of appendicitis in this age group, a high index of suspicion and early operation are important in avoiding perforation and subsequent morbidity.

Aged↗