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Biomedical subjects

Y Deng

Publications and source records attributed to Y Deng.

At least 217 records · Page 12Linked to original sources

Cosegregation of blood pressure with angiotensin converting enzyme and atrial natriuretic peptide receptor genes using Dahl salt-sensitive rats.

We have evaluated the genes for angiotensin converting enzyme (ACE) and guanylyl cyclase A/atrial natriuretic peptide receptor (GCA) for genetic effects on blood pressure response to high salt diet. In F2 rats derived from Milan normotensive and Dahl salt-hypertension sensitive (S) rats, both ACE and GCA cosegregated with blood pressure, and rats that were homozygous for the S allele at both the ACE and GCA loci had inordinately high blood pressure. In F2 derived from Wistar Kyoto (WKY) and S rats, GCA revealed positive cosegregation with blood pressure, but ACE did not. We conclude that certain alleles at the GCA and ACE loci (or at loci closely linked to them) have a significant genetic impact on blood pressure response to high salt in specific rat strains.

Animals↗

Identification and partial purification of a thiol endothelin-converting enzyme from porcine aortic endothelial cells.

Endothelin is a potent peptide vasoconstrictor. The final step in the processing of endothelin has been postulated to be the cleavage of the Trp21-Val22 peptide bond in proendothelin by a putative endothelin-converting enzyme. A soluble extract of primary porcine aortic endothelial cells was found to contain an enzyme activity that converted proendothelin-1 (proET-1) to an endothelin-1 (ET-1)-like peptide as determined by the rabbit aortic ring contraction assay. This enzyme was partially purified by DE52 ion-exchange chromatography. Incubation of proET-1 with the partially purified enzyme generated a product which had a retention time on HPLC identical to that of authentic ET-1. Further analysis of the product showed that it caused contraction of rabbit aortic rings, had a molecular weight identical to ET-1 as measured by fast atom bombardment mass spectrometry, and competed for [125I]ET-1 binding in an RIA using specific antibodies which recognize the carboxy terminal tryptophan of ET-1. The enzyme activity could be inhibited by thiol protease inhibitors such as Z-phe-pheCHN2 and p-hydroxymercuribenzoate, but not by serine- or metalloprotease inhibitors. The optimal pH for the enzymatic activity was between 7.0 and 7.5, and no activity was detected at pH 4.0. These results demonstrate that this thiol protease is a potential endothelin-converting enzyme.

Animals↗

A soluble protease identified from rat kidney degrades endothelin-1 but not proendothelin-1.

Endothelin-1 (ET-1) is a potent peptidic vasoconstrictor. This peptide has been shown to be cleared rapidly by the kidney. The purpose of the present study was to assess the involvement of renal proteolytic enzymes in the clearance/degradation of ET-1. Incubation of ET-1 with the cytosolic fraction of rat kidney homogenate resulted in a decrease of contractile activity on rabbit aortic rings when compared to the untreated ET-1. This cytosolic fraction was chromatographed by anion-exchange and concanavalin A columns. The partially purified enzyme cleaved off the C-terminal tryptophan of ET-1 rapidly, resulting in a peptide which is three orders of magnitude weaker in potency than ET-1 in causing smooth muscle contraction. In contrast, proendothelin-1 was not degraded by this endothelin degradation enzyme (EDE). The effects of EDE on other vasoactive peptides were also examined. The C-terminal tyrosine of atrial natriuretic peptide was cleaved by EDE, but the biological activity of the resulting peptide was not significantly changed. Angiotensin II was not a substrate for EDE. The EDE was shown to be different from both carboxypeptidases A and B based on the HPLC analysis of the degradation products of ET-1 produced by these enzymes. In addition, these enzymes displayed different sensitivities toward a carboxypeptidase inhibitor from potato tuber. These results suggest that this previously unidentified enzyme inactivates ET-1 effectively and that it may play a role in modulating the levels of ET-1 in the kidney.

Angiotensin II↗

Aggregative adherence fimbriae I of enteroaggregative Escherichia coli mediate adherence to HEp-2 cells and hemagglutination of human erythrocytes.

Strains of enteroaggregative Escherichia coli (EAggEC) have been implicated in several studies as important agents of persistent diarrhea among infants in the developing world. We have previously shown that the aggregative adherence (AA) property of EAggEC is associated with the presence of a 60-MDa plasmid which confers AA when introduced into E. coli HB101. Here, we report the cloning of the AA determinant from EAggEC strain 17-2 into the 21.5-kb cosmid vector pCVD301. TnphoA mutagenesis of the AA cosmid clone pJPN31 implicated an AA region of approximately 12 kb. Transmission electron microscopy of HB101 (pJPN31) revealed the presence of bundle-forming fimbriae, which were absent in AA- TnphoA insertion mutants. The presence of these fimbriae, AA, and hemagglutination (HA) of human erythrocytes were all concurrently lost by single-insertion mutations. A 14-kDa protein was seen on polyacrylamide gel electrophoresis and Western blotting (immunoblotting) of surface shear preparations from fimbriated clones. Twelve of nineteen volunteers fed EAggEC 17-2 developed rises in antibodies to the 14-kDa protein as determined by Western blot. We have termed the cloned bundle-forming fimbriae aggregative adherence fimbriae I (AAF/I); positivity with a previously described EAggEC probe and human erythrocyte HA appear to correlate with the presence of AAF/I.

Antibodies, Bacterial↗

Soluble endothelin degradation enzyme activities in various rat tissues.

From soluble extract of rat kidney we have previously identified an endothelin degradation enzyme that rapidly and specifically cleaves off the C-terminal tryptophan of endothelin-1, resulting in a peptide that is three orders of magnitude weaker in potency than endothelin-1 in causing smooth muscle contraction. The tissue distribution of this enzyme was examined, and the soluble extracts of rat kidney were found to contain the highest enzyme activity, followed by the spleen and the liver. In contrast, no enzyme activity was detected in the soluble extracts of brain, heart, and lung. The biochemical properties of the partially purified enzyme from kidney were further investigated. The optimal pH of the enzyme was between 5 and 7. The endothelin degrading activity was effectively blocked by thiol protease inhibitors such as benzyloxycarbonyl-Phe-Ala-diazomethyl ketone and p-hydroxymercuribenzoic acid, as well as by phenylmethylsulfonyl fluoride, but not by metalloprotease and other serine protease inhibitors. This enzyme displayed a clear difference in substrate specificity when compared with other thiol proteases such as cathepsin B, cathepsin H, and cathepsin L, known to be present in the kidney. These results suggest that a novel protease with endothelin degrading activity is widely distributed in a number of tissues.

Animals↗

The influence of calcium on ANF release in the isolated rat atrium.

We developed an in vitro model of the isolated, perfused rat atrium with which to examine the mechanisms linking muscular stretch to atrial natriuretic factor (ANF) secretion. It was shown that an increase in atrial pressure causing distension of the atria is associated with a rise in ANF secretion correlating with the degree of pressure load. Pressure-induced ANF secretion is enhanced by the calcium blocker nifedipine or omission of calcium from the perfusion buffer. The changes in atrial volume in response to a given pressure load are also more pronounced in the absence of calcium or following the addition of the calcium blocker. These data suggest that in nonbeating atria, stretch-induced ANF secretion does not rely on calcium influx.

Animals↗

Intermixing of resident Golgi membrane proteins in rat-hamster polykaryons appears to depend on organelle coalescence.

We have used the synchronized formation of a mixed cytoplasm upon heterokaryon formation as a model for investigating the cisternal-specific transport of resident proteins between neighboring Golgi apparatus. Rat NRK and hamster 15B cells were fused by UV-inactivated Sindbis virus and then incubated for various time periods in the presence of cycloheximide. The resident Golgi apparatus proteins, rat GIMPc and Golgp 125, were localized with species-specific monoclonal antibodies. Immunofluorescent colocalization of rat and hamster Golgi membrane proteins was observed with a t1/2 of 1.75 h at 37 degrees C. Colocalization of resident, but not transient, Golgi membrane protein was concomitant with formation of a large extended Golgi complex and was accompanied by the acquisition of endoglycosidase H resistance by preexisting Golgp 125. Dispersal of the extended Golgi complex by nocodazole revealed that colocalization of resident Golgi proteins was due to intermixing of proteins in the same Golgi element rather than overlapping of closely apposed Golgi structures. Incubation of the polykaryons at 20 degrees C inhibited both the colocalization of GIMPc and Golgp 125 and the formation of an extended Golgi complex. Little change in the number of cisternae/stack in cross sections of the Golgi apparatus was observed upon cell fusion, and in the extended Golgi complex the hamster resident protein remained localized to one side of the Golgi stack. Surprisingly, the morphological identity of the rat and hamster Golgi units appeared to be maintained in the heterokaryons. These results suggest that the intermixing of resident Golgi membrane proteins requires direct physical continuity between Golgi elements and that resident Golgi membrane proteins are preferentially excluded from the non-clathrin-coated transport vesicles budding from Golgi cisternae.

Animals↗

Indoor air pollution and pulmonary function in children.

Pulmonary function in winter time in 1,343 school children aged 10-13 years was measured in four cities located in northern and southern part of China. The results showed that FVC, FEV1, PEF, V75, V50 and V25 in children living in homes with coal stoves were decreased by 1.5-10.7% compared with children living in homes with gas or LPG stoves in Chengde and Shanghai. In contrast to this, no significant difference in pulmonary function was found in Shenyang and Wuhan. It suggested that this phenomenon was related to indoor air pollution, and partly related to passive smoking or outdoor air pollution.

Air Pollution, Indoor↗

Incidence and mortality rates of myocardial infarction in Chinese workers aged 40-59 in relation to coronary risk factors. Results of a Chinese prospective study (Wuhan Study) in comparison to the Göttingen Risk Incidence and Prevalence Study (GRIPS).

Some 2045 male Chinese industrial workers aged 40-59 years living in the city of Wuhan in the People's Republic of China were examined for coronary risk factors in the year 1983. The investigation included a patient history, clinical examination, and ECG and laboratory tests, with special attention to serum lipids. After 5 years, a follow-up investigation of the study group was carried out. The results were compared to the similarly designed German GRIPS project. In comparison to the German population, significantly lower levels for total-, LDL-, and VLDL-cholesterol, apolipoprotein B, triglycerides, uric acid, body mass index, and diastolic blood pressure were found in China. The percentage of smokers, however, was remarkably higher in China than in the Federal Republic of Germany. During the 5 year observation period in the Chinese sample, four subjects suffered from sudden death and four from nonfatal myocardial infarction; in the German study group three times as many fatal myocardial infarction and cases of sudden death and 7.5 times as many nonfatal myocardial infarctions were recorded. Nonfatal coronary heart disease and peripheral vascular disease were also observed less often in China. The incidence of cerebrovascular diseases was 1.5 times higher in China than in Germany. Whereas in Germany, total-, and LDL-cholesterol values were the major distinguishing parameters between infarction and reference groups, in China these values have thus far had no significant influence on the level of risk. Instead in the Chinese incidence group, significantly higher levels for blood pressure, body mass index, uric acid, and the ratio LDL/HDL-cholesterol were found.

Adult↗

[Effect of gentamicin on the concentration of calcium, magnesium and zinc in perilymph of the guinea pig].

The calcium, magnesium and zinc ions in perilymph of the guinea pig were measured after hearing loss induced by gentamicin. The concentration of the calcium ions and magnesium ions increased, the zinc ions decreased in perilymph. The ototoxicity of gentamicin was related to the changes of these electrolytes in inner ear circumstance. The results showed that the changes of ions were the step of gentamicin ototoxicity.

Animals↗

[Bullous retinal detachment and its classification of fluorescence angiography].

Nineteen cases with (27 eyes) of bullous retinal detachment, male (24 eyes), female (3 eyes), were reported. The age of onset was from 16 to 46, mean 36.7. All of them underwent fundus fluorescence angiography (FFA). According to the results of FFA, it could be divided into two types of fluorescence angiograph changes were seen: type I, multiple pigmental epithelial damage at posterior pole, it consisted of twelve cases (16 eyes); type II, extensive pigmental epithelial damage at posterior pole, it consisted of seven cases (11 eyes). The treatments consist: medicine; medicine and photocoagulation; combined medicine, transscleral drainage and photocoagulation. Among 27 eyes, 20 had their vision improved after treatment, 4 eyes unchanged and 3 eyes decreased in vision. 22 eyes obtained their retinal reattachment (81.4%). The diagnosis, differential diagnosis, classification and treatment are discussed.

Adolescent↗

A case of testosterone-secreting adrenal cortical adenoma with spironolactone body-like inclusion.

Testosterone-secreting adrenal adenoma is rare. We recently experienced a 17-year-old pubertal girl who showed signs of virilization and a high serum level of testosterone. The excised adrenal gland showed a 3.5 x 3 x 3-cm cortical adenoma. Light and electron microscopic findings together with the high serum level and high tumor tissue contents of testosterone and dehydroepiandrosterone (DHA) indicated that the tumor was a testosterone-secreting adrenal cortical adenoma. This appears to be a rather rare tumor from a review of the literature. Interestingly, in this case, the cytoplasm of the tumor cells contained structures resembling spironolactone bodies. From the results of enzyme histochemistry, the steroidogenetic pathways in this tumor were speculated.

Acid Phosphatase↗

[The role of substance P in electroacupuncture analgesia and its relation to enkephalins in the rat brain].

In order to understand the role of substance P (SP) in the brain and the relationship between SP and enkephalins in the electroacupuncture analgesia (EA), we have observed the influence of SP-antagonist, (D-Arg', D-Phe5, D-Trp7.9, Leu11) -SP (DADPDTL) injected intracerebroventricularly (icv) on EA and the change of the level of SP in the brain regions of the rat during EA. We have made a further observations on the influences of the naloxone (NX) on the che change of the content of SP induced by EA and DADPDTL on the increase in Leu-enkephalins (LEK) induced by EA. The Wistar rats were used in the experiment. The latency of the tail flick, immersing the tip of rat tail (4 cm) into hot-water of 50 degrees C, was taken as the pain threshold. The drugs were injected icv via plastic cannulae implanted in the bilateral ventricles. The EA was applied to the point of "Zusanli" (S36). The contents of SP and LEK were determined radioimmunoassay in the hypothalamus, mid-brain, striatum and pons-medulla-oblongata. The pain threshold was increased by 48 +/- 9% (P less than 0.01) after EA. But icv injection of DADPDTL decreased the pain threshold by 14 +/- 7% after EA. The result suggests that DADPDTL can antagonize the effect of EA and that SP in the brain is involved in EA. After EA the contents of SP in the hypothalamus and mid-brain of the rats were decreased by 29% and 28% in comparison with that of the control group respectively (both of them, P less than 0.05), but the contents of SP in the striatum and pons-medulla-oblongata had no significant change.(ABSTRACT TRUNCATED AT 250 WORDS)

Acupuncture Analgesia↗

[Relation of capsaicin-sensitive neurones to the effect of electro-acupuncture analgesia].

In this experiment, the rats treated with capsaicin (50 mg/kg) s. c. on day 2 of liqe were used 12 weeks after injection. The levels of substance P(SP) in sciatic nerves and dorsal spinal cords were measured with radioimmunoassay to evaluate the extent of C-afferent fibers damaged by capsaicin. The results as follows: (1) the levels of SP in the sciatic nerve and the dorsal spinal cord are decreased by 69% and by 62% respectively, indicating the degeneration of the primary C-afferent fibers is very massive; (2) the average of basal tail-flick latency (immersing in 50 degrees C water) is prolonged 105% as compared with the control; (3) after electro-acupuncture, the average of tail-flick latency of the capsaicin treated rats is increased by 81%, while that of the vehicle treated rats increased by 54%. These data suggest that C-afferent fibers substantially mediate the transmission of noxious thermal stimuli, but is unnecessary for the transmission of acupuncture message to induce analgesia.

Acupuncture Analgesia↗

[Inhibitory effect of bleomycin A6 on human colon cancer xenografts in nude mice].

As evaluated by clonogenic assay, bleomycin A6 was found to be highly active against established human cancer cell lines derived from colon cancer (HT-29) and cecum cancer (Hce-8693). These human cancer cells have been serially transplanted in nude mice. At a tolerable dosage level, bleomycin A6 exerted remarkable growth inhibition on human colon cancer HT-29 and cecum cancer Hce-8693 xenografts (approximately 90% inhibition). No histopathological changes were found in the organs of treated animals. Compared on the basis of equitoxic doses (1/9 LD50), bleomycin A6 exerted much stronger growth inhibition against colon cancer HT-29 xenografts in nude mice than 5-fluorouracil and mitomycin C, with inhibition rates of 82%, 12% and 53%, respectively. More extensive necrosis was found in tumors treated with bleomycin A6 than in those treated with mitomycin C or 5-fluorouracil. The ratio values of non-necrotic tumor tissue to whole tumor tissue for bleomycin A6, mitomycin C and 5-fluorouracil were 0.33, 0.65 and 0.57, respectively. These observations indicate that bleomycin A6 is a potent antitumor agent against colon cancer xenografts and may be useful in human colon cancer chemotherapy.

Animals↗