Biomedical subjects

C T Wang

Publications and source records attributed to C T Wang.

At least 19 recordsLinked to original sources

PubMed1997

Generation of infectious virus particles by transient co-expression of human immunodeficiency virus type 1 gag mutants.

We have demonstrated that COS7 cells transiently co-expressing myristylation-defective (Myr-) and protease-defective (PR-) human immunodeficiency virus (HIV) mutants can release infectious virions when co-transfected with an amphotropic murine leukaemia virus envelope protein expression plasmid (SV-A-MLV-env). In contrast, no infectious virions were detected when a PR-, noninfectious HIV gag mutant was co-expressed with the Myr- mutant, although the Myr- mutant could still process the immature core particles in trans. This result indicates that generation of functionally normal Gag proteins is required for virus infectivity in our complementation system. A mutant with a 56-amino-acid deletion in the N-terminal region of the capsid (CA) domain could still complement the PR- mutant to generate infectious virions, suggesting that the deletion mutant could provide a functional protease for processing in the PR- mutant. This result is consistent with the concept that mutations within the N-terminal region of the CA domain have no major effects on Gag-Pol incorporation into particles.

Animals↗

PubMed1997

Intrarenal production of angiotensin II.

The intrarenal renin-angiotensin system plays a critical role in the paracrine regulation of renal hemodynamics and tubular transport function. Much of the intrarenal angiotensin II (ANG II) is formed locally as evidenced by intrarenal ANG II contents that are much greater than can be explained from the circulating ANG II concentration. Intrarenal ANG II is formed from systemically delivered ANG I and from intrarenally formed ANG I derived from systemically delivered angiotensinogen as well as locally synthesized angiotensionogen. There is a regional distribution of intrarenal ANG II in that the medullary content per gram of tissue is four to five times higher than the cortical content. In addition, most of the cortical ANG II is compartmentalized in the renal interstitial fluid and in the tubular fluid. Proximal tubule cells contain all the components of the renin-angiotensin system necessary for synthesis and secretion of ANG II. Proximal tubule concentrations of ANG II as well as ANG I and angiotensinogen support the concept that the proximal tubule cells secrete ANG II or precursors of ANG II into the tubular fluid. The intratubular concentrations of ANG II are in the nanomolar range, indicating a substantial capability to influence luminal ANG II receptors on the tubule cell membranes. Thus, much of the ANG II-dependent actions on tubular transport functions could be due to specific effects of locally synthesized ANG II on luminal ANG II receptors. Experimental evidence shows that the intratubular ANG II concentrations are regulated independently of the circulating concentrations, but the specific mechanisms responsible remain to be delineated.

Angiotensin I↗

PubMed1996

Platelet lysis and functional perturbation by 13-methyl myristate. The major fatty acid in Flavobacterium ranacida.

Flavobacterium ranacida consisted of 75% of 13-methyl myristate in total fatty acids. The acid at > 60 microM caused the lysis of gel-filtered platelets (GFP) in both time- and concentration-dependent manners. Scanning electron microscopy showed that: 1). GFP in 40 microM of the acid changed the morphology to speculate discoid shape at 15 sec, and to ellipsoids after 30 sec; and 2), the cells gradually swelled to spherical forms as the concentration of the acid increased. At nonlytic concentration, the acid inhibited platelet responses to various agonists with differential concentrations. The order of inhibitory potency was U46619 > low dose collagen > ADP-fibrinogen > phorbol ester > high dose collagen. The results demonstrated that 13-methyl myristate exhibited both cell lytic activity and perturbation on membrane function.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1996

Sequences and comparisons of duck mitochondrial DNA control regions.

In this study, the nucleotide sequences of the displacement loop (D-loop) and the ribosomal RNA genes of mitochondrial DNA (mtDNA) were determined from a representative each of two genera of ducks, Cainina muschata and Anas platyrhynchos. The duck mtDNA shows a specific gene order at 5' upstream of D-loop (5'ND6-tRNA(Glu)-D-loop3') that is identical to chick mtDNA but is different from that of mammalian or amphibian (5' cytochrome b-tRNA(Thr)-tRNA(Pro)-D-loop3'). Nucleotide diversity is greatest in the D-loop while being most conserved in the 12S rRNA gene, as indicated from a sequence comparison between duck and chick mtDNA. A consensus sequence in the D-loop region, which may play influential roles in the regulation of transcription and replication of mtDNA, was found in both CSB-1 and repeated sequences of birds. Sequences of four tRNA genes in this region are also reported. Among them, tRNA(Glu) shows the greatest sequence divergence when different order of birds are compared.

Animals↗

PubMed1996

Clinical and hematological characteristics of hepatosplenic T gamma/delta lymphoma with isochromosome for long arm of chromosome 7.

Hepatosplenic T gamma/delta lymphoma is a rare entity of peripheral T cell lymphoma. Three of 386 patients with non-Hodgkin's lymphoma in our institute were found to have this subtype of lymphoma. All had chromosomal abnormalities of isochromosome 7q and trisomy 8. The clinical and hematological features of these three patients are reported. All were males with ages ranging from 23 to 29 years. Initial presentation comprised purpura and variable degree of hepatosplenomegaly. None had superficial lymphadenopathy. Hematologically, they showed pictures resembling immune related thrombocytopenia and/or hemolytic anemia. Examination of the bone marrows revealed hypercellularity with increased number of megakaryocytes and erythroid cells and various degrees of abnormal lymphoid cell infiltration. The histopathologic section of the spleen from one patient who underwent splenectomy revealed abnormal cell infiltration in the sinusoids of the red pulp. Lymphoma cells showed T gamma/delta lymphoid immunophenotype (CD3+ CD2+ CD4- CD8-, TCR delta-1+, and beta F1-). The platelet counts were elevated transiently after initial treatment with corticosteroids, but the condition soon deteriorated. All died of refractory lymphoma five to nine months after diagnosis. Review of the literature, showed that only four other cases have been reported until now and although no cytogenetic data were available for these patients, they had very similar clinical pictures as those in this series. It is suggested that hepatosplenic T gamma/delta lymphoma represents a rare, but distinct, clinicopathological and cytogenetic entity.

Adolescent↗

PubMed1996

Concentration of arsenic, selenium, zinc, iron and copper in the urine of blackfoot disease patients at different clinical stages.

Atomic absorption spectrophotometric methods were developed for the determination of arsenic, selenium, iron, zinc, and copper in the urine samples. Data collected from blackfoot disease patients at five clinical stages were compared with those from healthy controls. Spectrophotometry was also used to compare the concentrations and detection levels of these elements in blood and hair samples. The copper concentration in urine changed slightly for all clinical stages, whereas the concentrations in blood and hair showed less correlation with the stages of blackfoot disease. The zinc concentration in urine increased with the clinical stage, the fourth stage having the highest concentration. The zinc concentrations in urine were not correlated with those of blood and hair samples. Zinc appears to be associated with the occurrence of scaling and cracking of the skin of the fingers or feet, and is even closely correlated with the degree of ulceration and gangrene of blackfoot disease patients. The more advanced degrees of blackfoot disease patients were associated with a greater zinc concentration in the urine. Arsenic, which is claimed to be a major causative agent of blackfoot disease, increased from the zero stage and showed a particularly high concentration in the second stage. The arsenic concentration in urine showed a positive correlation with that in the blood and the hair. Arsenic is indicated as major causative agent of blackfoot disease. The selenium concentration decreased from the zero stage, showing its lowest value during the second stage, then increased in the later stages. Changes in the selenium concentration in the urine were the inverse of those observed for the arsenic concentration in blood and hair. The decrease of selenium is attributed to the antagonistic effect of arsenic; selenium is retained during the initial stages. Iron increased from the zero stage to the second stage and showed the highest concentration of all the measured elements. It then decreased in the advanced stages of the disease. Iron may have an interactive effect with arsenic in the initial stages, resulting in loss of haemoglobin during the advanced stages. The antagonistic effect of selenium and the interactive effect of iron on arsenic warrant further study.

Arsenic↗

PubMed1995

Dopamine release in the nucleus accumbens during sexual behavior in prenatally stressed adult male rats.

In vivo microdialysis experiments were performed on the nucleus accumbens (NAc) during observation of sexual behavior (including motivation and copulation) to determine if there were any changes in NAc dopamine (DA) transmission in prenatally stressed (PS) adult male rats. Approximate 37% of control males and 83% of PS males did not exhibit copulation during the sexual behavior tests and no significant changes in NAc DA release were seen during exposure to estrous females. In contrast, both control and PS males that displayed copulatory behavior showed a marked increase in NAc DA release when presented with a sexually receptive female behind a screen and this increased further during actual copulation. The increase in DA release in copulatory PS males was not significantly different from that in sexually active control males. In addition, a similar extent in DA release induced by high potassium perfusate was observed in all rats. These results suggest that prenatal stress may result in a deficit in DA neurotransmission in the NAc and this deficit may possibly cause impaired male sexual behavior in rats.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Effects of age on dopamine release in the nucleus accumbens and amphetamine-induced locomotor activity in rats.

The effects of age on dopamine (DA) release in the nucleus accumbens (NAc) and on amphetamine (AMPH)-induced locomotor activity were studied by microdialysis in freely-moving young (5 month) and old (24 month) rats. Both basal extracellular DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release and that following intra-accumbens perfusion of AMPH (1-10 microM) were significantly lower in old rats. After intraperitoneal injection of AMPH (1.5 mg/kg), no age-related change in DA release was seen in the NAc, but locomotor activity was found to increase much more in young rats than in old ones. These results indicate that (1) old rats show decreased extracellular DA and DOPAC release, both in the basal state and following intra-accumbens infusion of AMPH, and (2) the age-related locomotor activity induced by systemic injection of AMPH is not paralleled by changes in DA release in the NAc.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Assembly of HIV GAG-B-galactosidase fusion proteins into virus particles.

We have studied the assembly of human immunodeficiency virus (HIV-1) Gag-B-galactosidase (Gag-B-gal; GBG) fusion proteins into HIV particles in the presence of HIV Gag proteins. Release of fusion proteins from cells was measured by assay of media versus cellular B-gal activities and was dependent on co-expression of unfused Gag proteins. Gag-B-gal incorporation into virus particles was demonstrated by detergent treatment and density gradient fractionation studies and was dependent on protein-protein interactions requiring the C-terminal two-thirds of the HIV CA domain. The central MA domain appeared unimportant for fusion protein incorporation; a nonmyristylated GBG protein was incorporated but at a relatively reduced level, while the NC and p6 domains slightly affected the assembly of fusion proteins into particles. Subcellular fractionation studies showed that all fusion proteins including the nonmyristylated one were enriched in the cytoplasmic pellet fraction. However, assembly into particles did not correlate with subcellular fractionation patterns. Similarly, virion incorporation levels of Gag-B-gal proteins did not correlate with their immunofluorescence localization patterns. However, we observed that while most fusion proteins displayed a perinuclear ring with heterogeneous staining throughout cells, short fusion proteins appeared enriched on the intracellular membranes, and fusion proteins with intact MA but deleted NC domains showed an enhanced surface staining without a clear perinuclear ring. Altogether, our data suggest that the CA domain is the primary determinant for assembly of HIV fusion proteins into virus particles.

Animals↗

PubMed1994

Activation of human platelet phospholipases C and A2 by various oxygenated triterpenes.

Eight structural analogues of oxygenated triterpenes exerted striking differences in activation of human platelets. They are four pairs of stereoisomers and two pairs of positional isomers with varying: 1) acetoxyl/hydroxyl substituents; 2) the position of the substituents at C-3 and C-15; and 3) the stereochemistry of a substituent at C-3. It required a threshold concentration for each agent to cause the concentration-dependent activation. These triterpenes were hydrophobic with < 20% difference in the partition coefficients between 1-octanol and water. They caused differential effects on: inositol triphosphate production; the increase in [Ca2+]i; diacylglycerol formation; phosphatidic acid accumulation, protein phosphorylations and arachidonate release. These agents activated both phospholipases C and A2. The trend of activating phospholipase C was triterpenes with two acetoxyl substituents > one acetoxyl/one hydroxyl substituents > two hydroxyl substituents. In activating phospholipase A2, triterpenes with two acetoxyl substituents were most effective, whereas the paired isomers with a hydroxyl group at C-15 alpha and an acetoxyl substituent at C-3 failed the activation. The results enable one to discuss the possible structure-activity relationship of various oxygenated triterpenes in the activation of both phospholipases C and A2.

Arachidonic Acid↗

PubMed1994

Studies on the concentrations of arsenic, selenium, copper, zinc and iron in the hair of blackfoot disease patients in different clinical stages.

Flame atomic absorption spectrophotometric methods were developed for, arsenic, selenium, copper, zinc and iron in hair samples. Data from blackfoot disease patients at five clinical stages were compared with those from healthy controls. The copper and zinc concentrations showed only slight differences in all clinical stages, which indicated the less relation to blackfoot disease. The decrease of selenium and iron in all stages was attributed to the antagonistic effect of arsenic; arsenic increased in the first and second stages, but decreased in the later stages. The decrease of selenium and iron during the progression of the disease is thought to be due to persistence of the antagonistic effect of arsenic in the initial stages, so that very low concentrations of selenium are found in the advanced stages, despite the later decrease of arsenic. There was also a progressive decrease of iron with advance of the disease, and the later stages also showed a decrease in haemoglobin. It was shown that arsenic is a major cause of blackfoot disease, and that it antagonises selenium and iron, which decreased in the advanced clinical stages of the disease.

Aged↗

PubMed1994

Separation of Chinese Leishmania isolates into five genotypes by kinetoplast and chromosomal DNA heterogeneity.

Leishmaniasis remains endemic in China, especially in the west and northwest frontier regions in central Asia. Epidemic outbreaks of both visceral and cutaneous forms of the disease have become a serious concern in view of such events occurring in neighboring countries. In the present study, we have begun to characterize available parasites as an initial step in understanding the epidemiology of leishmaniasis in central Asia. Nineteen Leishmania isolates collected since the 1950s from epidemiologically different foci in China were separated into five genotypes (Groups I-V) based on their polymorphisms in both kinetoplast (kDNA) and nuclear (nDNA) DNAs. Both kDNA and nDNA are conserved in Group I, which consists of six isolates, i.e., five cases of human kala-azar and one case of canine leishmaniasis isolated from three distant foci more than 30 years apart. In contrast, both kDNA and nDNA are heterogeneous in Group II, consisting of 10 isolates scattered in the plain area from the eastern coast to the western desert. This group includes five kala-azar cases, one post-kala-azar dermal leishmaniasis case, two sand fly isolates, and two canine isolates. The remaining three groups (III-V), two from great gerbils (Rhombomys opimus) and one from a kala-azar case, differ among themselves and from the aforementioned groups. Groups I, II/III, IV, and V contain isolates that have been recognized epidemiologically or typed isoenzymatically as L. donovani s.l., L. infantum s.l., L. turinica, and L. gerbilli, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

[Hyperdynamic status in a partial portal vein ligated (PVL) rat's portal hypertension model].

The splanchnic and systemic hemodynamics were measured by radioactive microsphere techniques in a PVL rat's model with portal hypertension. The portal-hypertensive rats (1.75 +/- 0.24 vs. 1.23 +/- 0.13 kPa, P < 0.001) with greater than 93% portal-systemic shunting had an increase in portal venous inflow by 50% (8.97 +/- 0.8 vs. 6.03 +/- 0.28 ml.min-1.100gBW-1; P < 0.001) and a concomitant decrease by 40% in splanchnic arteriolar resistance (0.27 +/- 0.05 vs. 0.42 +/- 0.05kPa.ml-1.min-1.100gBW-1; P < 0.01) compared with control rats. Cardiac index (54.6 +/- 4.4 vs. 36.5 +/- 3.0 ml.min-1.100gBW-1) was elevated by 50% (P < 0.001), and total peripheral resistance (0.052 +/- 0.006 vs. 0.084 +/- 0.009 kPa.ml-1.min-1.100gBW-1) was decreased by 40% (P < 0.001). The resistance to portal blood flow in portal vein-stenotic rats (0.087 +/- 0.011kPa.ml-1.min-1) was similar to that in control rats (0.076 +/- 0.01kPa.ml-1.min-1), indicating that the hyperdynamic portal venous inflow, not resistance, was the mainstay of the elevated portal venous pressure. Which is in favor of the forward flow theory of portal hypertension. The systemic hemodynamic parameters were secondary to the splanchnic hemodynamic changes.

Animals↗

PubMed1993

Treatment of filarial lymphoedema and elephantiasis with 5,6-benzo-alpha-pyrone (coumarin).

OBJECTIVE: To study efficacy of treatment of filarial lymphoedema and elephantiasis with 5,6-benzo-alpha-pyrone. DESIGN: Randomised, double blind, placebo controlled study with matching for grade and duration of disease, age, and sex. Treatment was given for 367 days, and subjects were followed up for another year. SETTING: A town in Shandong Province, China. SUBJECTS: 104 men and women with chronic unilateral filarial lymphoedema or elephantiasis of the leg: 64 were randomised to benzopyrone and 40 to placebo. By the end of the study 19 patients had dropped out of the treatment group and two out of the placebo group. INTERVENTIONS: Two 200 mg tablets of 5,6-benzo-alpha-pyrone or two placebo tablets given daily. MAIN OUTCOME MEASURES: Volumes of the affected and normal legs estimated every three months, and daily listing of any side effects. RESULTS: Benzopyrone reduced oedema for all grades of lymphoedema during the year of treatment (pW0.001) and the follow up year (p = 0.026). During treatment the mean monthly reductions in leg volume were 0.62% (95% confidence intervals 0.4% to 0.85%), 1.1% (0.71% to 1.6%), and 1.6% (0.89% to 2.3%) of the volume of the normal leg for grades 1, 2, and 3-5 (elephantiasis) of lymphoedema respectively. During follow up the mean monthly reductions were 0.18% (0.01% to 0.35%), 0.54% (0.27% to 0.82%), and 0.87% (0.51% to 1.2%). At the end of the trial the total reduction in oedema was 100%, 95%, and 45% for grades 1, 2, and 3-5. Symptoms and complications were considerably reduced, including attacks of secondary acute inflammation, while side effects were minor and disappeared after one month. In the placebo group there were no changes in the severity of lymphoedema. CONCLUSIONS: 5,6-benzo-alpha-pyrone reduces the oedema and many symptoms of filarial lymphoedema and elephantiasis. It has few side effects, and its relatively slow action makes it ideal for use without compression garments.

Coumarins↗

PubMed1993

The mode of action of primary bile salts on human platelets.

Cholate and its conjugated amide derivatives glycocholate and taurocholate solubilized human platelets differently as studied by the observations on: (1) the change in optical absorbance of platelet suspension, (2) marker leakiness and (3) component solubility. Cholate ruptures the membrane in an all-or-none process, while both conjugated derivatives shed off both proteins and lipids. The shed lipids formed vesicles and could be separated from the proteins. The conjugated salts gradually chop off the cell membrane into pieces causing the cells to become small spheres (1.5 microns in diameter) as revealed by scanning electron microscopy, which also revealed that morphological change of platelet in these bile salts depended on both concentration and incubation period. Platelets at the prelytic-stage concentration of these three salts deformed initially to spiculate disc and finally to a stretched-out flat form. Also, in the prelytic stage of these bile salts, platelets showed inhibited responses to thrombin which did not happen to platelets in deoxycholate (Shiao et al. (1989) Biochim. Biophys. Acta 980, 56-68.).

Bile Acids and Salts↗

PubMed1993

Conditional infectivity of a human immunodeficiency virus matrix domain deletion mutant.

We constructed a human immunodeficiency virus (HIV) matrix (MA) deletion mutant by deletion of about 80% of the HIV type 1 Gag MA domain but retaining myristylation and proteolytic processing signals. The effects of this deletion matrix (dl.MA) mutant on HIV particle assembly, processing, and infectivity were analyzed. Surprisingly, the dl.MA mutant still could assemble and process virus particles, had a wild-type (wt) retrovirus particle density, and possessed wt reverse transcriptase activity. RNase protection experiments showed that dl.MA mutant particles preferentially packaged viral genomic RNA. When both mutant and wt particles were pseudotyped with an amphotropic murine leukemia virus envelope protein, mutant infectivity was about 10% of wt level. In contrast, infectivity of the dl.MA mutant was 1,000-fold less than that of wild-type when mutant and wt particles were pseudotyped with the HIV envelope protein. Protein analyses of pseudotyped virions indicated that there were no major differences between mutant and wt viruses in the efficiency of amphotropic murine leukemia virus envelope protein incorporation. In contrast, there was a reduction in the amount of mutant particle-associated HIV envelope protein gp120. Our results suggest that an intact HIV matrix domain is not absolutely required for reverse transcription, nuclear localization, or integration but is necessary for appropriate HIV envelope protein function.

Amino Acid Sequence↗

PubMed1993

Assembly, processing, and infectivity of human immunodeficiency virus type 1 gag mutants.

We studied the effects of gag mutations on human immunodeficiency virus type 1 (HIV-1) assembly, processing, and infectivity by using a replication-defective HIV expression system. HIV mutants were screened for infectivity by transduction of a selectable marker and were examined for assembly by monitoring particle release from transfected cells. Gag protein processing and reverse transcriptase activities of mutant particles were also assayed. Surprisingly, most Gag protein mutants were assembled and processed. The two exceptions to this rule were a myristylation-minus mutant, and one gag matrix domain mutant which expressed proteins that were trapped intracellularly. Interestingly, a mutant with a 56-amino-acid deletion within the HIV gag capsid domain still could assemble and process virus particles, exhibited a wild-type retrovirus particle density, and had wild-type reverse transcriptase activity. Indeed, although most HIV-1 gag mutants were noninfectious or poorly infectious, they produced apparently normal particles which possessed significant reverse transcriptase activities. These results strongly support the notion that the HIV-1 Gag proteins are functionally involved in post-assembly, postprocessing stages of virus infectivity.

Amino Acid Sequence↗

PubMed1993

Studies on the concentration of arsenic, selenium, copper, zinc and iron in the blood of blackfoot disease patients in different clinical stages.

Flame atomic absorption spectrophotometric methods were developed for the determination of zinc, copper, arsenic, iron and selenium in blood samples. Data from blackfoot disease patients in five clinical stages were compared with those from healthy controls. Copper concentrations were the same for all clinical stages. Arsenic increased in the initial three stages but decreased thereafter, although arsenic was previously considered to be the major causative agent of the disease. The decrease of arsenic in the later stages was attributed to the antagonistic effect of selenium, and the decrease of iron during the progress of the disease is thought to be due to the antagonistic effect of arsenic in the initial stages and the loose of haemoglobin in the later stages.

Aged↗