Biomedical subjects

Y Huang

Publications and source records attributed to Y Huang.

At least 739 records · Page 41Linked to original sources

PubMed1997

Fluorescence microscopic comparison of the binding of phosphodiester and phosphorothioate (antisense) oligodeoxyribonucleotides to subcellular structures, including intermediate filaments, the endoplasmic reticulum, and the nuclear interior.

To detect potential intracellular binding sites for antisense oligodeoxyribonucleotides (ODN), 3'-fluorescence-tagged phosphodiester (P) and phosphorothioate (S) analogs of a series of model and vimentin and actin antisense ODN were applied to digitonin-permeabilized fibroblast and epithelial PtK2 cells. Fluorescence microscopy revealed binding of the ODN to intermediate filaments (IFs) with a preference for cytokeratin IFs, cytoplasmic membranes (endoplasmic reticulum), and, above all, the nuclear interior. The affinity of the ODN for these cellular substructures was dependent on their base composition, and the S-ODN were by far superior to the corresponding P-ODN in binding activity. Fluorescence polarization measurements of the interaction of ODN with purified IF proteins in vitro confirmed the differential, high-affinity binding of S-ODN to IFs. In permeabilized cells, the ODN readily migrated into the nucleus where, at ambient temperature, preferentially the S-ODN gave rise to a multitude of large, irregular aggregates. Nuclear uptake of the ODN was considerably and differentially inhibited by wheat germ agglutinin. High-affinity S-ODN, but not P-ODN, additionally reacted with a structure presumably identical with the nuclear lamina. Simultaneously, they cause decompaction of chromatin, whereby the S-ODN aggregates appeared as compact inclusions in homogeneously dispersed chromatin. After microinjection of S-ODN into intact cells, these effects were not observed, although the nucleic acids rapidly moved into the nucleus and condensed into a large number of well-defined, spherical speckles or longitudinal rodlets. The methylphosphonate analogs of some of the ODN used exhibited only extremely low affinities for intracellular constituents. These results show that excess amounts of S-ODN saturate a host of both low-affinity and high-affinity binding sites on cellular substructures, whereas limited quantities as used for microinjection recognize only the high-affinity binding sites. The results support the notion that the nonsequence-specific, often toxic effects of antisense S-ODN result from their strong binding to cellular components and substructures involved in replicational, transcriptional, and translational processes. On the other hand, the association of the ODN with membranes and cytoskeletal and karyoskeletal elements may serve to optimize their sequence-specific interaction with their intended target sites and also increase their cellular retention potential. These cellular structures would thus fulfill a depot function.

Actins↗

PubMed1997

Effects of putative K+ channel blockers on beta-adrenoceptor-mediated vasorelaxation of rat mesenteric artery.

The aim of our study was to investigate the contribution of Ca(2+)-activated K+ channels (KCa channels) and ATP-sensitive K+ channels (KATP channels) to the vasodilator responses to beta-adrenoceptor agonists in the rat isolated mesenteric artery. Isoprenaline and fenoterol concentration-dependently relaxed the phenylephrine-precontracted endothelium-intact arterial rings with 50% inhibitory concentration (IC50) of 0.0314 +/- 0.027 microM (n = 20) and 0.40 +/- 0.04 microM (n = 11), respectively. Charybdotoxin (100 nM) displaced the isoprenaline or fenoterol logarithmic concentration-relaxation curve to the right in the absence and presence of endothelium. In contrast, glibenclamide (10 microM) did not affect the effects of isoprenaline and fenoterol, whereas glibenclamide (3 microM) significantly inhibited the cromakalim-induced vasorelaxation. Neither charybdotoxin (100 nM) nor glibenclamide (10 microM) influenced the vasorelaxation induced by forskolin. Ba2+, a nonselective blocker of K+ channels, inhibited the relaxant effects of isoprenaline and forskolin. These results suggest that KCa but not KATP channels contribute to beta-adrenoceptor-mediated vasodilator response in rat mesenteric artery, and cyclic adenosine monophosphate (cAMP) might not be involved in regulation of the activity of KCa channels.

Adenosine Triphosphate↗

PubMed1997

Representations of graphomotor trajectories in the human parietal cortex: evidence for controlled processing and automatic performance.

The aim of this study was to identify the cerebral areas activated during kinematic processing of movement trajectories. We measured regional cerebral blood flow (rCBF) during learning, performance and imagery of right-hand writing in eight right-handed volunteers. Compared with viewing the writing space, increases in rCBF were observed in the left motor, premotor and frontomesial cortex, and in the right anterior cerebellum in all movement conditions, and the increases were related to mean tangential writing velocity. No rCBF increases occurred in these areas during imagery. Early learning of new ideomotor trajectories and deliberately exact writing of letters both induced rCBF increases in the cortex lining the right intraparietal sulcus. In contrast, during fast writing of overlearned trajectories and in the later phase of learning new ideograms the rCBF increased bilaterally in the posterior parietal cortex. Imagery of ideograms that had not been practised previously activated the anterior and posterior parietal areas simultaneously. Our results provide evidence suggesting that the kinematic representations of graphomotor trajectories are multiply represented in the human parietal cortex. It is concluded that different parietal subsystems may subserve attentive sensory movement control and whole-field visuospatial processing during automatic performance.

Adult↗

PubMed1997

Primer tRNA3Lys on the viral genome exists in unextended and two-base extended forms within mature human immunodeficiency virus type 1.

In human immunodeficiency virus type 1, tRNALys3 is placed upon the primer binding site, where it serves as the primer for reverse transcription. We show herein that genomic placement occurs independently of precursor protein processing and that the placed tRNALys3 exists in two major forms: unextended or in a form extended by the first two DNA bases incorporated, C and T. The two-base extended form of the tRNALys3 is absent in a protease-negative mutant, indicating a requirement for mature viral proteins to initiate reverse transcription within the virus.

Animals↗

PubMed1997

The roles of the human immunodeficiency virus type 1 Pol protein and the primer binding site in the placement of primer tRNA(3Lys) onto viral genomic RNA.

Factors that modulate the placement of primer tRNA(3Lys) onto the viral RNA genome in human immunodeficiency virus type 1 (HIV-1) were investigated through analysis of reverse-transcribed products that are extended from the tRNA(3Lys) primer. Mutations were introduced into the HIV-1 pol gene to result in the appearance of a stop codon in the open reading frame of the reverse transcriptase (RT) gene. These constructs, BH10-RT1 and BH10-RT2, yielded viruses with truncated Pol proteins. Alternatively, we altered the sequences involved in frameshifting by generating the construct BH10-FS. With each of these mutated viruses, we found that the primer tRNA(3Lys) that was placed onto viral genomic RNA was present in an unextended state. In contrast, as expected, tRNA(3Lys) in the case of wild-type BH10 virus had been extended by 2 bases. Furthermore, the amount of tRNA(3Lys) that was placed onto viral RNA in mutated viruses was significantly less than that placed in the wild-type virus. We also generated a mutant within the polymerase-active site of RT (D185H) (Asp-->His) that eliminated RT polymerase activity. We found that the placement of primer tRNA(3Lys) onto viral genomic RNA was independent of enzyme function; however, the tRNA(3Lys) that was placed was present in an unextended state due to the loss of RT activity. In contrast, the elimination of protease activity through a D25A (Asp-->Ala) point mutation in the protease-active site (construct BH10-PR) did cause a drop in the efficiency of tRNA(3Lys) placement. In this situation, a proportion of the placed tRNA(3Lys) was found to be extended by 2 bases, although not to the extent found with wild-type virus (BH10), due to a decrease in RT activity associated with unprocessed Gag-Pol protein that could not be cleaved because of the loss of protease activity. We also investigated the role of the primer binding site (PBS) in the placement of tRNA(3Lys) through a series of 2-, 4-, and 8-nucleotide (nt) deletions at the 3' end of the PBS, i.e., BH10-PBS2, BH10-PBS4, and BH10-PBS8, respectively. In mutated viruses BH10-PBS2 and BH10-PBS4, the 2-base-extended form of tRNA(3Lys) was still detected. However, less primer tRNA(3Lys) was placed onto viral genomic RNA as more nucleotides were deleted until the percentage of placement seen with wild-type BH10 virus dropped to only 4% in the virus with 8 nt deleted (BH10-PBS8). Consistently, these mutated viruses possessed decreased initial replication capacity compared with that of the wild-type virus, with the extent of incapacity corresponding to the size of the deletion. However, after several days, an increase in replication potential was accompanied by a reversion to a wild-type PBS.

Animals↗

PubMed1997

Identification of a replication-competent pathogenic human immunodeficiency virus type 1 with a duplication in the TCF-1alpha region but lacking NF-kappaB binding sites.

Multiple human immunodeficiency virus type 1 (HIV-1) sequences with deletions of NF-kappaB binding sites at both the 5' and 3' long terminal repeats (LTRs) were identified in serial samples collected from an infected individual. The effect of this deletion on the level of transcription was studied by transient transfection of an LTR-driven luciferase reporter gene and by infection with a full-length recombinant HIV-1 containing a luciferase reporter (HIVHXBluc). Detectable levels of gene expression were found in both systems, in the presence or absence of the viral transactivator Tat. Interestingly, a duplication of a putative TCF-1alpha motif was found in place of the NF-kappaB elements in these viruses. Higher transcriptional activity was observed with HXBLTR (NF-kappaB intact) than with the patient's LTR (NF-kappaB deleted), suggesting that the NF-kappaB binding sites may promote optimal levels of viral gene transcription. The ability of these viruses with NF-kappaB deleted to replicate and cause substantial decline in CD4 cell counts demonstrates that the NF-kappaB binding sites are not absolutely required for viral replication or pathogenicity in vivo. These results are consistent with the notion that the HIV-1 LTR possesses functional redundancy which allows it to interact with multiple transcription factors, thereby ensuring viral replication in a variety of cell types.

Base Sequence↗

PubMed1997

Effect of mutations in the nucleocapsid protein (NCp7) upon Pr160(gag-pol) and tRNA(Lys) incorporation into human immunodeficiency virus type 1.

COS-7 cells were transfected with DNAs containing mutations in the NCp7 sequences of human immunodeficiency virus. Selective incorporation into the virus of tRNA(Lys) was measured by two-dimensional polyacrylamide gel electrophoresis, and Pr160(gag-pol) incorporation into the virus was detected in Western blots of viral protein. Mutations tested included cysteine and histidine mutations in either of the Cys-His boxes, as well as mutations in the N- and C-terminal flanking regions and in the linker region between the two Cys-His boxes. Of 10 mutations tested, only 2 inhibited tRNA(Lys) incorporation: a P31L mutation in the linker region and a deletion which removed both Cys-His boxes and the linker region (deltaK14-T50). The P31L mutation prevents the incorporation of Pr160(gag-pol) into the virus. Cotransfection of COS cells with both P31L DNA and a plasmid coding only for unprocessed Pr160(gag-pol) resulted in the viral incorporation of Pr160(gag-pol) and the rescue of selective packaging of tRNA(Lys) into the virion. In the deltaK14-T50 mutant, Pr160(gag-pol) is incorporated into the virus. Selective tRNA(Lys) packaging is not rescued by cotransfection with a plasmid coding for Pr160(gag-pol) but is rescued by cotransfection with DNA coding for wild-type Pr55(gag). Since Pr55(gag) does not by itself selectively package tRNA(Lys), the deltaK14-T50 mutation may be affecting tRNA(Lys) binding to a cytoplasmic Pr55(gag)/Pr160(gag-pol) complex.

Amino Acid Sequence↗

PubMed1997

Genotypic and phenotypic characterization of long terminal repeat sequences from long-term survivors of human immunodeficiency virus type 1 infection.

Human immunodeficiency virus type 1 (HIV-1)-infected individuals who remain asymptomatic despite prolonged infection present a unique opportunity to understand virologic and immunologic factors involved in the pathogenesis of AIDS. We have previously identified a group of long-term survivors (LTS) who are clinically healthy and immunologically normal despite 13 to 15 years of HIV-1 infection. In this study, we examined the 5' long terminal repeat (5' LTR) sequences in eight of these LTS. A total of 29 nucleotide sequences were obtained from their peripheral blood mononuclear cells (PBMC). Analysis of these sequences revealed no gross deletions within the 5' LTR. Seven of the eight subjects shared nearly identical consensus sequences in the binding sites for NF-kappaB, Sp1, and the viral trans-activator Tat. In multiple samples from one individual (Pt 5), however, G-to-A hypermutations were found throughout the entire region, suggesting a genetically defective 5' LTR. The effects of the observed genetic variations on LTR transcription were studied by transient transfection of an LTR-driven luciferase reporter gene and by infection with a full-length recombinant HIV-1 containing a luciferase reporter (HIVHXBLTRluc). A wide range of basal and Tat-induced transcriptional activities was found among the 5' LTR from seven of the eight LTS in both transfected 293 cells and donor PBMC, suggesting a functionally intact 5' LTR in these individuals. It is therefore unlikely that defects in the 5' LTR are the underlying explanation for the benign clinical course associated with these seven individuals. However, functional abnormalities were found in the LTR from Pt 5 in directing both heterologous and viral gene expression, providing a possible genetic explanation for the low viral load and prolonged asymptomatic state of this individual. Last, a similar overall degree of genetic diversity was found among viruses from the LTS compared to those from patients with AIDS, reinforcing the notion that a strong correlation between the degree of genetic diversity and the rate of disease progression is unlikely.

Base Sequence↗

PubMed1997

Myocardial perfusion reserve: assessment with multisection, quantitative, first-pass MR imaging.

PURPOSE: To demonstrate the feasibility of determining myocardial blood flow changes and the myocardial perfusion reserve with magnetic resonance (MR) first-pass imaging, to validate the MR results by means of comparison with radiolabeled microsphere flow measurements in an animal model, and to compare the coronary flow reserve with the perfusion reserve at MR imaging in patients with hemodynamically nonsignificant coronary lesions and angina. MATERIALS AND METHODS: Arrhythmia-insensitive, first-pass, multisection, T1-weighted MR imaging with contrast agent enhancement was performed in eight pigs with acute ischemia and in eight adult patients (six women, two men). In the pigs, microsphere flow measurements were obtained in parallel with the MR measurements. In the patients, the coronary flow reserve was measured with an intracoronary Doppler flow ultrasound probe for comparison with the MR perfusion reserve. RESULTS: In the animal studies, there was linear correlation between MR perfusion indexes and the microsphere flow measurements (r = .88, P < .01). In the patients, the regional perfusion reserve matched the coronary flow reserve (linear regression with a slope of 1.02 +/- 0.09, r = .80). CONCLUSION: The myocardial perfusion reserve can be quantified with first-pass MR imaging. In patients with microvascular dysfunction, the myocardial perfusion reserve matches the reduced coronary flow reserve.

Animals↗

PubMed1997

Roles of cytoplasmic Ca2+ and intracellular Ca2+ stores in induction and suppression of apoptosis in S49 cells.

The Ca2+-ATPase inhibitors, thapsigargin and cyclopiazonic acid, depleted intracellular Ca2+ stores, induced large increases in intracellular Ca2+ concentration, and caused apoptosis in S49 cells. Removal of extracellular Ca2+ augmented apoptosis due to thapsigargin, indicating that depletion of Ca2+ from intracellular stores is responsible for apoptosis with this agent. Overexpression of the apoptosis suppressor, Bcl-2, inhibited apoptosis due to thapsigargin but did not affect thapsigargin-induced Ca2+ signaling. Dexamethasone induced apoptosis, diminished the size of the endoplasmic reticulum Ca2+ pool, and caused a small elevation of intracellular Ca2+. However, this elevation was not due to Ca2+ influx because the increase was similar in the presence or absence of Ca2+ in the medium. Furthermore, in contrast to the results with thapsigargin, apoptosis due to dexamethasone was unchanged in a Ca2+-free medium. These results indicate that depletion of Ca2+ stores initiates a pathway leading to apoptosis. Elevations in cytoplasmic Ca2+ appears to play a lesser role than previously thought in the actions of Bcl-2 and glucocorticoids.

Apoptosis↗

PubMed1997

A fiber matrix model for the filtration through fenestral pores in a compressible arterial intima.

We advance a new hypothesis to explain the changes in hydraulic conductivity of an intact artery wall with transmural pressure previously observed by Tedgui and Lever [Am. J. Physiol. 247 (Heart Circ. Physiol. 16): H784-H791, 1984] and Baldwin and Wilson [Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H26-H32, 1993]. This hypothesis suggests that compaction due to pressure loading of the proteoglycan matrix in the arterial intima near fenestral pores of the internal elastic lamina (IEL) leads to a narrowing of the pore entrance area and a large decrease in local intrinsic Darcy permeability of the matrix. To quantitatively assess the feasibility of this mechanism, a local two-dimensional model is proposed to study filtration flow in the vicinity of fenestral pores in a compressible intima. Using a heterogenous fiber matrix theory, we first predict the change in Darcy permeability with intimal thickness (Li). The model then calculates local velocity profiles and pressure distributions in the intima and media. The results show a marked nonlinear steepening of intimal pressure profiles near fenestral pores when the intima thins at higher luminal pressures. The predicted relative change in resistances of the IEL (with intima, R(I)) and of the media (Rm) shows a steep increase in R(I)/Rm when Li is <20% of its unstressed value. Numerical results also suggest that intimal compression has a limiting behavior in which the much stiffer collagen fibrils inhibit further compaction at high pressures after the proteoglycan matrix is maximally compressed. Predictions are also presented to show how different transmural pressures alter growth of an intimal horseradish peroxidase spot that derives from a localized (a single cell's boundary) endothelial leakage. Such a prediction is amenable to experimental verification.

Animals↗

PubMed1997

Inhibitory effect of amitriptyline on contraction of the rat isolated trachea.

The effects of amitriptyline, a tricyclic antidepressant, on contractile responses to exogenously applied acetylcholine, endothelin 1 and high K+ were examined in the rat isolated trachea. Amitriptyline (0.3-30 mumol/l) produced a shift to the right of the logarithmic acetylcholine concentration-contraction curve without affecting the maximum contraction. Amitriptyline (10-100 mumol/l) significantly reduced the maximal contractile response to endothelin 1. The IC50 values were 10.3 and 30.2 mumol/l for inhibition of the submaximal contractile response to 1 mmol/l acetylcholine and to 50 nmol/l endothelin 1, respectively. Amitriptyline inhibited the high K+ (60 mmol/l)-evoked contraction with an IC50 of 0.225 mumol/l. The inhibitory effect of amitriptyline was unchanged by the K+ channel blockers, charybdotoxin (100 nmol/l) and glibenclamide (up to 10 mumol/l). These results indicate that amitriptyline could antagonize the effect of acetylcholine and also exert direct inhibitory effect on muscle contraction of the rat trachea as a nonselective muscle relaxant.

Acetylcholine↗

PubMed1997

Effects of genotype and diet on cholesterol efflux into plasma and lipoproteins of normal, apolipoprotein A-I-, and apolipoprotein E-deficient mice.

We investigated the contribution of apoE to cholesterol efflux into plasmas of normal, apoA-I-, and apoE-deficient mice, which were fed with chow- and cholesterol-rich diets. Plasmas of normal and apoA-I-deficient mice contain apoE in pre-beta-migrating VLDL as well as in HDL-like lipoproteins, which have either electrophoretic alpha- or gamma-mobilities. The latter particle resembled gamma-LpE in human plasma also by its mobility on nondenaturing two-dimensional electrophoresis. No apoE-containing lipoproteins were found in plasmas of apoE-deficient mice. When apoA-I- and apoE-deficient mice received both chow- and fat-rich diets, their plasmas released significantly less 3H-cholesterol from radiolabeled fibroblasts than did plasma of normal mice. Removal of apoE from plasmas of normal and apoA-I-deficient mice by anti-apoE immunoaffinity chromatography decreased their cholesterol efflux capacities (per 1 minute/per 1 hour) by 26%/40% (P = 0.0092/0.0007) and 30%/26% (P = 0.0092/0.0003), respectively. Net cholesterol efflux from fibroblasts into apoA-I-deficient plasma was 45% lower compared with plasma of normal mice. Incubation of fibroblasts with apoE-deficient plasma caused net influx of cholesterol. Prior addition of human apoE to or removal of apoB-containing lipoproteins from apoE-deficient plasma restored its ability to cause net cholesterol efflux to 50% of normal plasma. Some of the differences between cholesterol efflux into normal and apoE-deficient plasmas were attributable to the failure of apoE-deficient plasmas to take up cell-derived 3H-cholesterol into gamma-LpE. Compared with normal plasma, both apoA-I-deficient and apoE-deficient plasmas were significantly decreased in their activity to esterify cell-derived 3H-cholesterol. Anti-apoE chromatography decreased significantly cholesterol esterification in normal plasma and apoA-I-deficient plasma but not in apoE-deficient plasma. Taken together, the data provide evidence that apoE is an important contributor to reverse cholesterol transport, partially because of initial uptake of cell-derived cholesterol by gamma-LpE and partially because of the contribution of apoE-containing lipoproteins to esterification of cholesterol in plasma.

Animals↗

PubMed1997

Genetic factors precipitating type III hyperlipoproteinemia in hypolipidemic transgenic mice expressing human apolipoprotein E2.

Several factors are hypothesized to precipitate or exacerbate type III hyperlipoproteinemia (HLP) in humans. Among such factors are those that directly overload remnant lipoprotein production or disrupt removal pathways, including an increased ratio of apolipoprotein (apo) E2 to normal apoE, overproduction of apoB-containing lipoproteins, and decreased LDL receptor activity. Hypolipidemic apoE2-transgenic mice bred onto an apoE-null background had dramatically higher plasma total cholesterol (192 +/- 26 mg/dL for males, 203 +/- 40 mg/dL for females) and triglyceride (295 +/- 51 mg/dL for males, 277 +/- 58 mg/dL for females) levels than apoE2 mice with endogenous mouse apoE. Thus, eliminating normal apoE in the presence of apoE2 (thereby increasing the relative abundance of the defective ligand) can convert a hypolipidemic to a hyperlipidemic phenotype. Hypolipidemic apoE2 transgenic mice overexpressing human apoB had moderate remnant accumulation compared with apoE2-only or apoB-only transgenic mice, indicating that overproduction of apoB-containing lipoproteins in the presence of apoE2 can augment remnant production. Hypolipidemic apoE2 transgenic mice bred-onto an LDL receptor-null background had markedly higher plasma total cholesterol (288 +/- 51 mg/dL for males, 298 +/- 73 mg/dL for females) and triglyceride (356 +/- 72 mg/dL for males, 317 +/- 88 mg/dL for females) levels than apoE2-only mice, and remnant accumulation increased even in apoE2 mice with a heterozygous LDL receptor-knockout background (compared with apoE2-only mice), suggesting that reducing or eliminating a major receptor-mediated remnant-removal pathway in the presence of apoE2 can also precipitate a hyperlipidemic phenotype. In all cases where either lipoprotein remnant production or removal pathways were severely stressed, increased remnant accumulation was apparent. As judged by the chemical characteristics of the remnant lipoproteins, the lipoprotein phenotype was quite similar to that of human type III HLP, especially in the apoE2-expressing mice with no endogenous apoE or LDL receptors, and thus these mice represent improved models of the disorder.

Animals↗

PubMed1997

Vascular lesions in Chinese patients with transient ischemic attacks.

We studied 96 Chinese patients with TIAs using transcranial Doppler and duplex ultrasonography. We found intracranial stenosis or occlusion in 51% of cases and extracranial disease in 19% of cases. The most common intracranial lesion was stenosis of the terminal internal carotid artery or proximal middle cerebral artery, whereas the most common extracranial lesion was stenosis of the carotid bifurcation.

Adolescent↗

PubMed1997

[Recent progress on analytical chemistry and biochemistry of D-amino acids].

Recent findings that D-amino acids, especially D-aspartic acid and D-serine, exist in vivo in the mammalian tissues (brain and peripheries), prompted us now to investigate their biological and pathological roles in mammals. In this review, the overview of the progress of analytical chemistry and biochemistry of D-amino acids is described.

Animals↗

PubMed1997

Effects of zinc gluconate on nephrotoxicity and glutathione metabolism disorder induced by cis-platin in mice.

To examine the effects of zinc gluconate (ZG) on the nephrotoxicity of cis-platin (CDDP), changes in renal function and glutathione metabolism were investigated in mice. Fifty mice were randomly divided into five equal groups: controls, CDDP group and three ZG plus CDDP groups; the dose of ZG was 100 mg, 140 mg and 180 mg/kg respectively. Mice were sacrificed after 48 hours of CDDP (9 mg/kg) treatment; the levels of serum creatinine (Cr) and blood urea nitrogen (BUN) were measured, the glutathione (GSH) and malondialdehyde (MDA) content and the activities of glutathione peroxidase (GHS-PX) and catalase (CAT) in whole blood and renal tissue were assayed. Compared to the control group, there were significant increases in Cr, BUN and MDA, and decreases in the activities of GSH-PX in the CDDP group in whole blood and renal tissue. Preadministration of ZG at the doses of 140 mg/kg and 180 mg/kg significantly increased the concentration of GSH in whole blood, and decreased the levels of Cr and BUN, and the MDA content in whole blood and renal tissue, compared with the CDDP group. We conclude that preadministration of ZG might improve renal function and glutathione metabolism and reduce the nephrotoxicity of cis-platin.

Animals↗

PubMed1997

Antitumor effects and pharmacological interaction of xiao-chai-hu-tang (sho-saiko-to) and interleukin 2 in murine renal cell carcinoma.

Conventional therapy for renal cell carcinoma using interleukin 2 (IL-2) has shown limited antitumor action. The purpose of our study was to investigate synergistic antitumor effects of IL-2 and Xiao-Chai-Hu-Tang (XCHT), and to elucidate the mechanisms of interaction between the two drugs against the murine renal cell carcinoma cell line, Renca, in vivo. The treatment was started 5 days after subcutaneous transplantation of Renca tumor. XCHT was given at a dose of 2.5 g/kg daily for 30 days orally. IL-2 was given at a dose of 10(4) U/mouse by subcutaneous injection every other day 8 times. Combination of XCHT and IL-2 inhibited growth of the tumor and prolonged survival significantly as compared with the untreated mice. Increased cellular infiltration was observed in tumor tissue and the lungs of mice treated with XCHT alone and by combination of XCHT and IL-2, but there were no histological changes in the liver and kidney. Elevation of serum IL-6 was observed in tumor-bearing mice, but IL-6 was significantly suppressed by administration of XCHT. The results obtained suggest that combination of XCHT and IL-2 induces enhanced immunological reaction in specific organs and tissues, and IL-6 may have a role in the synergistic effect of these two agents. It was concluded that combination of XCHT and IL-2 is useful in the treatment of patients with renal cell carcinoma.

Animals↗