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Yuan Li

Publications and source records attributed to Yuan Li.

At least 181 records · Page 10Linked to original sources
PubMed2003

[Differentially expressed genes in hepatocellular carcinoma of tree shrew induced by different factors].

BACKGROUND & OBJECTIVE: Previous studies on differentially expressed genes in hepatocellular carcinoma (HCC) used to perform with para-cancerous tissues as normal control. However, the para-cancerous tissue of HCC is actually abnormal because they frequently contain hepatitis, cirrhosis, hyperplastic nodules or foci, etc. In order to explore the molecular mechanism and the responsible genes for hepatocarcinogenesis, through applying the HCC model of tree shrew (Tupaia belangeri chinensis), this study was designed to compare gene expression levels between HCC induced by different factors and their corresponding biopsies taken before HCC formation. METHODS: Tree shrews were divided into two groups. Group AFB(1) was fed with aflatoxin B1 (AFB(1)). Group AFB(1)+HBV was infected firstly with human hepatitis B virus (HBV) and then fed with AFB(1) as group AFB(1). Serum tests for HBV markers and liver biopsies were performed periodically during the experiment. After appearance of HCC, 2 HCC samples from each group and their corresponding 30th-week biopsies were tested respectively by cDNA microarray assay. The gene expression levels were compared between each HCC and the corresponding biopsies, and the differentially expressed genes from the two groups of HCC induced by different factors were analyzed. RESULTS: The incidence rates of HCC in group AFB(1) and group AFB(1)+HBV were 73.3% and 77.8%, respectively. A considerable number of genes in both groups showed changes in their expression levels, which were mainly up-regulated in group AFB(1) but down-regulated in group AFB(1)+HBV. On the other hand, among the 588 checked genes (16 functional classifications) that were known related to human cancer, 11 genes were similarly expressed in all of the 4 HCC from the two animal groups. Most of these 11 genes belonged functionally to 3 types, namely "apoptosis-associated protein","DNA synthesis,repair and recombination proteins", and "growth factors, cytokines and chemokines". CONCLUSION: (1)HBV can affect AFB(1)-induced gene expression in certain extent. (2)The gene expression profiles of HCC induced by different factors are different. (3)The common differentially expressed genes in these two HCC groups are worthwhile for further study as the possibly responsible genes for hepatocarcinogenesis.

Aflatoxin B1↗
PubMed2003

Alteration of the p53 gene during tree shrews' hepatocarcinogenesis.

OBJECTIVE: To detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1). METHODS: Tree shrews were divided into four groups: group A, infected with HBV and fed with AFB1; group B, only infected with HBV; group C, fed with AFB1 alone; and group D normal control. The tree shrews underwent liver biopsy every 15 weeks. Liver and tumor tissues were detected by immunohistochemistry and molecular biotechnologies. RESULTS: The incidence of hepatocellular carcinoma (HCC) was higher in group A (66.7%) than in groups B (0) and C (30%). HCC occurrence was earlier in group A than in group C (120.0+/-16.6 wk vs 153.3+/-5.8 wk, t=3.336, P<0.01). Mutated p53 protein was not found in all groups before 75 weeks of experiment. At the 105th week, the expression rates of mutated p53 protein were 78.6%, 60.0% and 71.4% in groups A, B and C respectively, which were significantly higher than that in group D (10%) (chi2> or =5.03, P<0.05). An abnormal band of the p53 gene was detected in groups A and C. The mutational points of the p53 gene in liver cancer of tree shrews were at codon 275, 78 and 13. Nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 were 91.7% and 93.4% in homology compared with those of human p53, respectively. CONCLUSIONS: Remarkable synergistic effect on HCC exists between HBV and AFB1. Mutated p53 protein expressed before occurrence of HCC promotes the development of HCC. HBV and AFB1 may synergistically induce p53 gene mutation.

Animals↗
PubMed2003

[The expression of DNA methyltransferase DNMT1, 3A and 3B in acute leukemia and myelodysplastic syndrome].

OBJECTIVE: To explore the relationship between methyltransferases and the pathogenesis of acute leukemia (AL) and the leukemic transformation of myelodysplastic syndromes (MDS). METHODS: Semi-quantitative RT-PCR method was used to detect the mRNA expression level of DNMT1, 3A and 3B in bone marrow cells from 75 patients with AL or MDS. RESULTS: There was no significant difference in mRNA expression level of DNMTs between a low-risk MDS group (n = 21) and a normal group. However, increased expression level of DNMT1, 3A and 3B was found in 47.6%, 47.6% and 42.9% of the patients in the low-risk group, respectively, if the upper limit of 80% of the normal controls was considered as the critical level. In high-risk MDS (n = 13), a more proportion of the cases with increased expression level of DNMTs were found, that was 53.8%, 76.9% and 92.3% respectively, and only expression level of DNMT3B was significantly higher than that in the low-risk MDS group (P < 0.01). In the AL group (n = 41) expression level of all the three subtypes was coordinately higher than that in the MDS group (P < 0.01), companying with a more frequency of 92.7%, 97.6% and 100%. Comparing with the AML group, a significantly increased expression level of DNMT1 (P < 0.01) with the same level of DNMT 3A and 3B was interestingly observed in the ALL group. CONCLUSIONS: It is possible that up-regulated DNMTs contribute to the pathogenesis of AL and the leukemic transformation of MDS, and DNMT3B might be the most important enzyme among the three subtypes.

DNA (Cytosine-5-)-Methyltransferase 1↗
PubMed2003

[Diagnosis and treatment of osteopathic parathyroid adenoma].

OBJECTIVE: To introduce the advanced diagnostic technologies and share the surgical experience of parathyroid adenoma. METHODS: From November 1986 to August 2000, 9 patients with parathyroid adenoma who underwent operations were analyzed retrospectively. Out of them, there were 3 males and 6 females and their ages ranged from 12 to 55 years with an average of 32 years. The average disease course was 4 years and 9 months. General decreased density of the bone cortex and subperiosteum absorption were found in all 9 cases, while multi bone cyst lesion in 3 cases; obsolete fracture in 5 cases, including 2 cases of nephrolithiasis. Before operation, one child bore claudication and the other 8 patients suffered from disability. Serum parathyroid hormone (PTH) level increased markedly in 5 patients examined (633.87-1,017.40 pmol/L, normal value: 28.50-90.50 pmol/L). Radionuclide scan showed that imagings of parathyroid adenoma appeared in 3 patients. RESULTS: Parathyroid adenoma was resected via neck approach in 7 cases, and by way of sternum in the other 2 of the adenomas located in the chest. Parathyroid adenoma was diagnosed pathologically in 9 cases. All the 9 patients had no relapse during the 2-16 years of follow-up, with apparent relief of ostealgia and the normal serum PTH level, and roentgenogram showed fracture healing, great alleviation of the osteopathia. CONCLUSION: PTH examination as an advanced technique plays an important role in the differential diagnosis of hypercalcaemia. Color Doppler and radionuclide scan can locate the lesion. It is vital to judge the nature of the lesion by naked eyes, while frozen slices serves as a necessity to confirm. Enough parathyroid tissue should to be remained to assure normal parathyroid function. The variable number and ectopic possibility of parathyroid glands should be considered. Both the short-term and long-term surgical outcome of parathyroid adenoma are satisfactory.

Adenoma↗
PubMed2003

[Cloning and identification of the priming glycosyltransferase gene involved in exopolysaccharide 139A biosynthesis in Streptomyces].

Recently in our laboratory, Streptomyces sp. 139 has been identified to produce a new exopolysaccharide designated EPS 139A that shows anti-rheumatic arthritis activity. The strategy of studying EPS 139A biosynthesis is to clone the key gene in the EPS biosynthesis pathway, i.e. the priming glycosyltransferase gene catalyzing the first step of nucleotide sugar transfer. Degenerate primers-based PCR approach was adopted to isolate the putative priming glycosyltransferase gene in Streptomyces sp. 139. According to the genes encoding the priming glycosyltransferases that have been identified in several microorganisms, a multiple alignment of the amino acid sequences of these genes was used to identify regions conserved between all genes. To clone the priming glycosyltransferase gene in Streptomyces sp. 139, degenerate primers were designed from these conserved regions taking into account information on Streptomyces codon usage to amplify an internal DNA fragment of this gene. A distinctive PCR product with the expected size of 0.3 kb was amplified from Streptomyces sp. 139 total genomic DNA. Sequence analysis showed that it is part of a putative priming glycosyltransferase gene and contains the predicted conserved domain B. To isolate the complete priming glycosyltransferase gene, a Streptomyces sp. 139 genomic library was constructed in the E. coli--Streptomyces shuttle vector pOJ446. Using the 0.3 kb PCR product of priming glycosyltransferase gene as a probe, 17 positive colonies were isolated by colony hybridization. A 4.0 kb BamHI fragment from all positive cosmids that hybridized to this probe was sequenced, which revealed the complete priming glycosyltransferase gene. The priming glycosyltransferase gene ste5 (GenBank under accession number AY131229) most likely begins with GTG, preceded by a probable ribosome binding site (RBS), GGGGA. It encodes a 492-amino-acid protein with molecular weight of 54 kDa and isoelectric point of 10.6. The G + C content of ste5 is 73%, close to the average of G + C content (74%) for Streptomyces. Moreover, the preference usage of G or C as third base of codons are found in the ste5, which is in accordance with the Streptomyces codon usage. A BlastP search showed that the C-terminal region of Ste5 shows highly homology with a number of priming glycosyltransferases from many different organisms. Ste5 contains two putative catalytic residues, Glu and Asp (residues 423 and 474) with a spacing of approximately 50 amino acids that conserved in various beta-glycosyltransferases. Moreover, the C-terminal one third of Ste5 contains three domains, A, B and C that is reported to be common to glycosyltransferases. By hydrophilicity plot prediction, the N-terminal two thirds of Ste5 exhibits 5 putative transmembrane domains. To investigate the involvement of the identified polysaccharide gene cluster in EPS 139A biosynthesis, the gene ste5 encoding priming glycosyltransferase was insertionally disrupted by a single-crossover homologous recombination event. A 0.85 kb internal fragment of ste5 was cloned into vector pKC1139 to yield pLY5015 that was transduced into Streptomyces sp. 139. Correct integration in Streptomyces LY1001 ste5- mutant strain was confirmed by Southern hybridization. After fermentation, no EPS 139A could be detected in the cultures of ste5- mutant strain Streptomyces LY1001. Therefore, the gene ste5 identified in this work is involved in the synthesis of the Streptomyces sp. 139 EPS.

Amino Acid Sequence↗
PubMed2003

[Effect of erythromycin on the expression of apoptotic gene on eosinophils in nasal polyps in vitro].

OBJECTIVE: To study the expression of apoptotic gene in nasal polyps and the possible effect of erythromycin on it. METHODS: Total 40 nasal polyps biopsies were detected the expression of Bcl-2, Bax, Bcl-xL as well as Fas protein on eosinophils by immunohistochemistry. The expression of Bax, Bcl-xL, Fas on eosinophils in 15 nasal polyps explants which cultured with or without erythromycin were detected also. RESULTS: In nasal polyps, the expression of Bcl-2, Bax, Bcl-xL and Fas protein on eosinophils are 5% (2/10), 65% (26/40), 40% (16/40) and 90% (36/40) respectively. As compared with inferior turbinate, there were significant difference in expression of Bax and Fas protein between two tissues (P < 0.05). After cultured with erythromycin, the expression of Bax protein increased (P < 0.05), but the expression of Bcl-xL and Fas protein had not changed. CONCLUSION: Bax may be the most significant gene which control the apoptosis of eosinophils in nasal polyps. And a possible mechaism which erythromycin promote the apoptosis of eosinophils is increase the expression of Bax.

Adolescent↗
PubMed2003

[Protective efficacy of DNA vaccines encoding mycobacterium tuberculosis Ag85B protein].

AIM: To explore protective efficacy of pTB30m and pTB30s encoding Ag85B protein against infection with M. tuberculosis H (37)R (v). METHODS: BALB/c mice were infected intravenously with 5x10(5) CFU of M. tuberculosisH (37)R (v) six weeks after the last vaccination of pTB30m and pTB30s. At the same time, normal BALB/c mice were injected intravenously with 5x10(6) T cells separated from immunized BALB/c mouse spleen through nylon wool column, and challenges were injected with 10(5) CFU of M. tuberculosis immediately intravenously. After 4 weeks, the CFU in spleens of infected mice were counted respectively. RESULTS: Vaccination with pTB30m and pTB30s produced significant protection against M. tuberculosis proliferation in the mouse spleens following challenge. As compared with the saline-injected mice, CFU in spleens of the mice vaccinated with pTB30m or pTB30s were reduced significantly, being 0.645(log(10) CFU, P<0.01) and 0.839(log(10) CFU, P<0.001), respectively. In contrast, bacterial load in the mice spleens vaccinated with empty plasmid only had little reduction. After adoptive immunization by T cells from the mice vaccinated with pTB30m and pTB30s, the mice might induce partial protection against M. tuberculosis proliferation in the mouse spleens following challenge. CONCLUSION: Protective efficacy of the mice immunized with pTB30s against challenge with M. tuberculosis virulent strain was better than that immunized with pTB30m.Thus, pTB30s is a promising DNA vaccine with respect to the prevention and treatment of tuberculosis.

Acyltransferases↗
PubMed2003

[Construction and identification of the E.coli-BCG shuttle vector expressing lipoprotein Der p2 on cell wall of mycobacterium vaccae].

AIM: To construct the E.coli-BCG shuttle vector carrying and expressing dust mite antigen gene Der p2 on cell wall of mycobacterium vaccae. METHODS: The gene fragment encoding 19 kDa antigen and the upstream control element (19-ss) was amplified by PCR from the mycobacteria tuberculosis H37Rv.Subsequently, the 19-ss gene was cloned into the E.coli-BCG shuttle vector pOLYG, which can schlepped and expressed exogenous antigen gene on cell wall of mycobacteria and containing the Der p2 gene. The expression of Der p2 gene in mycobacterium vaccae determined by indirect immunofluorescence staining. RESULTS: Sequencing proved that the cloned sequence of 19-ss gene was correct. The constructed E.coli-BCG shuttle vector (pCW) containing 19-ss gene had function of shuttle between E.coli and mycobacteria, and mediated the expression of antibiotic resistance gene. Indirect immunofluorescence staining indicated that the Der p2 gene was expressed in the form of lipoprotein on surface of the mycobacterium vaccae. CONCLUSION: E.coli-BCG shuttle vector has been constructed successfully, which can express exogenous antigen gene as a chimeric protein on cell wall.

Cell Wall↗
PubMed2003

[Effects of Th1 cytokine gene on anti-CFP10 antibody production in BALB/c mice induced by Mycobacterium tuberculosis DNA vaccine].

AIM: To investigate the effects of plasmid containing mouse IL-12 and human IL-18 genes on the humoral immune response of mice immunized by CFP10 gene of Mycobacterium tuberculosis (MTB) H(37)R(v) strain. METHODS: Human IL-18 cDNA was amplified from RNA of PBMCs by RT-PCR and cloned into the pGEM-Teasy vector. After sequencing it was subcloned into the the sites of BamH I and EcoR I digestion of pcDNA3.1. BALB/c mice were injected intramuscularly by eukaryotic expression plasmid pcmIL12 and pcIL18, together with MTB CFP10 DNA vaccine, respectively. The same immunization repeated three times at intervals of two weeks. Mouse sera were collected at two weeks after the each injection. The titer of anti-CFP10 antibody was detected by ELISA. RESULTS: IL-18 cDNA was amplified successfully from RNA of human PBMCs by RT-PCR and the result of sequencing was correct. The IL-18 gene was correctly inserted into the vector pcDNA3.1 by being confirmed with BamH I and EcoR I digestion analysis, positive plasmid was called pcIL18. After being immunized with pcCFP10 three times, the end point titer of anti-CFP10 was 1:4 000, while the titer obtained by being immunized with pcIL18 + pcCFP10 was 1:8 000, but yet, after being immunized with pcmIL12+pcCFP10, the end point titer of anti-CFP10 antibody was only 1:200. CONCLUSION: Combination of IL-18 gene with MTB CFP10 DNA vaccine can enhance the humoral immune responses to pcCFP10, whereas the immunization with IL-12 gene plus pcCFP10 made humoral immune response markedly descent. As for whether IL-18 gene plus MTB CFP10 DNA vaccine can induce markedly the cellular mediated immune response to CFP10 or not remains to be further investigated.

Animals↗
PubMed2003

[Effects of perindopril on plasma soluble TRAIL and receptor soluble DR5 in patients with congestive heart failure].

AIM: To explore the levels of soluble TRAIL and DR5 in plasma of patients with congestive heart failure (CHF) and the effects of perindopril. METHODS: 58 CHF patients were randomly divided into two groups, namely perindopril treatment group (30 cases) and routine treatment group (28 cases). The levels of sTRAIL and sDR5 in plasma of 30 CHF patients treated with perindopril, 28 CHF patients treated with routine method before and after treatment and 20 healthy persons were detected by ELISA. RESULTS: (1)The mean levels of sTRAIL in plasma of 58 CHF patients and 20 healthy persons were (1.43+/-0.47) microg/L and (0.93+/-0.12) microg/L, respectively, the comparison between the patients and healthy persons had no notable difference (P>0.05), suggesting that plasma sTRAIL level had no significant relation to injured level of cardiac function. As for sDR5 level, the mean level in plasma of 58 CHF patients was (39.67+/-6.78) ng/L, this value was significantly higher than that of healthy control group, and the level of sDR5 was increased with the injured level of cardic function.(2)The plasma levels of sTRAIL in both perindopril group and conventional treatment group decreased after treatment, but there was no significant difference. The mean levels of plasma sDR5 in perindopril group were (31.23+/-10.16 ) ng/L and (8.50+/-2.14) ng/L; the levels in conventional group (48.81+/-8.74) ng/L and (26.64+/-6.27) ng/L, respectively, the perindopril group was lower than the conventional group descending rates were 72.7% and 45.3% respectively.(3)The level of plasma sDR5 in CHF patients resulting from hypertensive cardiopathy was much higher than that in CHF patients resulting from any other etiological factors. CONCLUSION: DR5 may play an important role in the occurrence and progress of myocardium apoptosis of CHF patients. Perindopril can down-regulate the level of plasma sDR5, therefore, it may have the great effect on retarding course of ventricular remodeling, protecting and improving cardial function of CHF patients.

Apoptosis↗
PubMed2003

[Serial pathologic changes in livers of Tree shrews and Macaca assamensises infected with human Hepatitis B virus].

BACKGROUND: To serially observe the pathologic changes in livers of tree shrews and macaca assamensises infected with HHBV. METHODS: 10 adult tree shrews and 28 macaca assamensises were inoculated with HBV rich human sera. The liver of the animals were regularly biopsied. The liver samples were examined histopathologically by HE staining. Some samples were stained for HBsAg by immunohistochemistry (IH), and HBV DNA by in situ hybridization (ISH). RESULTS: HBsAg in 80% of tree shrews infected with HHBV can be detected by IH, HBV DNA in 50% of those can be found by ISH.The positive rates of HBsAg in macaca assamensises' livers were 25% by IH, none HBV DNA was detected. CONCLUSION: The tree shrew model seems to be applicable for the research of human hepatitis B.

Animals↗
PubMed2002

[Retrospective comparative analysis of intranasal endoscopic resection of sinonasal tumors].

OBJECTIVE: To investigate the effectiveness and indication of intranasal endoscopic resection of sinonasal benign tumors. METHODS: A retrospective comparative study was made of intranasal endoscopy among twelve patients with benign tumors and twelve patients with inverting papilloma of the nose and paranasal sinuses between October 1996 and June 2001. A follow-up was made for ten months to five years. RESULTS: Of the twelve cases of benign tumors, five cases of hemangioma including one case of nasopharyngeal angiofibroma, one case of fibroma and one case of neurofibroma as well as one case of benign fibromatosis of nasal ethmoid sinus were completely excised without any evidence of recurrence so far. Of the four patients with ossifying fibromas, two cases with ethmoid sinus invasion underwent successful total removal without any recurrence three years after operation, one case was completely ablated after second procedure and another case had her tumor subtotally resected with symptom remission. Of the twelve cases of inverting papilloma among which two patients had cancerated, eight achieved complete resection at first attempt, and the remaining four cases having either persistence or recurrence of tumor also got cured via endoscopic YAG laser or revision procedure. All these 12 patients except one were followed up for two to five years without any recurrence. CONCLUSION: With excellent visualization, a less operative invasiveness and no scar on face the endoscopic approach appears to be the method of choice for the treatment of some benign tumors including inverting papilloma of nose and paranasal sinuses.

Adult↗
PubMed2002

Inactivation of enhanced expression of G(i) proteins by pertussis toxin attenuates the development of high blood pressure in spontaneously hypertensive rats.

We have previously shown that the enhanced expression of G(i) proteins in spontaneously hypertensive rats (SHR) that precedes the development of high blood pressure may be one of the contributing factors in the pathogenesis of hypertension. In the present study, we demonstrate that the inactivation of G(i) proteins by intraperitoneal injection of pertussis toxin (PT, 1.5 micro g/100 g body wt) into 2-week-old prehypertensive SHR prevented the development of hypertension up to 4 weeks and that, thereafter, it started to increase and reached the same level found in untreated SHR after 6 weeks. A second injection of PT after 4 weeks delayed the increase in blood pressure for another week. The PT-induced decrease in blood pressure in 6-week-old SHR was associated with a decreased level of G(i)alpha-2 and G(i)alpha-3 proteins in the heart, as determined by in vitro ADP ribosylation and immunoblotting. The decreased level of G(i) proteins was reflected in decreased G(i) functions. Furthermore, an augmentation of blood pressure to the same level in PT-treated SHR as found in untreated SHR was associated with enhanced expression and function of G(i). These results indicate that the inactivation of G(i) proteins by PT treatment in prehypertensive SHR attenuates the development of hypertension and suggest that the enhanced levels of G(i) proteins that result in the decreased levels of cAMP and associated impaired cellular functions may be contributing factors in the pathogenesis of hypertension in SHR.

ADP-Ribosylation Factors↗
PubMed2002

Modulation of ANP-C receptor signaling by endothelin-1 in A-10 smooth muscle cells.

We have previously shown that pretreatment of A-10 smooth muscle cells (SMC) with angiotensin II (Ang II) attenuated atrial natriuretic peptide (ANP) receptor-C (ANP-C)-mediated inhibition of adenylyl cyclase without altering (125)I-ANP binding. In the present studies, we have investigated the modulation of ANP-C receptor signaling by endothelin-1 (ET-1). Pretreatment of A-10 SMC with ET-1 for 24 h attenuated the expression of ANP-C receptor by about 60% as determined by immunoblotting which was reflected in attenuation of ANP-C-receptor-mediated inhibition of adenylyl cyclase. C-ANP(4-23) [des(Gln(18),Ser(19),Gln(20),Leu(21),Gly(22))ANP(4-23)-NH(2)], a ring-deleted peptide of ANP that interacts specifically with ANP-C receptor, inhibited adenylyl cyclase activity in a concentration-dependent manner with an apparent K(i) of about 1 nM in control cells. The maximal inhibition observed was about 30% which was almost completely attenuated in ET-1-treated cells. In addition, Ang II- and oxotremorine-mediated inhibitions of adenylyl cyclase were also attenuated by ET-1 treatment; however, the expression of Gialpha-2 and Gialpha-3 proteins and not of Gsalpha and Gbeta proteins was augmented by such treatment. The increased expression of Gialpha-2 and Gialpha-3 proteins by ET-1 treatment was inhibited by actinomycin D treatment (RNA synthesis inhibitor). On the other hand, the Gsalpha-mediated effects of some agonists on adenylyl cyclase activity were significantly decreased by ET-1 treatment. These results suggest that ET-1-induced downregulation of ANP-C receptor and not the overexpression of Gi proteins may be responsible for the attenuation of C-ANP(4-23)-mediated inhibition of adenylyl cyclase activity. From these studies it may be suggested that the downregulation of ANP-C receptors by increased levels of endothelin in vivo may be one of the possible mechanisms for the pathophysiology of hypertension.

Adenylyl Cyclase Inhibitors↗
PubMed2002

Selective killing of cancer cells based on translational control of a suicide gene.

The translation initiation factor, eIF4E, is commonly overexpressed in solid tumors. This elevation allows for efficient translation of mRNA that are normally repressed by their 5' untranslated region, many of which encode growth-promoting proteins. This property was exploited to modulate the synthesis of HTK at the translational level to selectively kill cancer cells. Various breast cancer cell lines can efficiently synthesize HTK from the translationally regulated mRNA, whereas normal cells cannot. Accordingly, only cancer cells were killed at low concentrations of ganciclovir. By altering the expression of eIF4E, it was possible to modulate the sensitivity of various cell lines to ganciclovir.

Antiviral Agents↗
PubMed2002

HIV enhances substance P expression in human immune cells.

Substance P (SP), a potent modulator of neuroimmunoregulation, is expressed in human immune cells. We observed elevated plasma SP levels in HIV-infected men compared with uninfected subjects. In the present study, we investigated the possible cellular source of the increased SP level caused by HIV infection. Using real-time reverse transcriptase-polymerase chain reaction, we demonstrated that monocyte-derived macrophages (MDM) and lymphocytes from both placental cord blood and adult peripheral blood expressed SP mRNA, which was significantly increased by HIV infection. HIV-induced SP expression was positively related to virus replication in the infected MDM. Purified recombinant HIV envelope glycoprotein 120 (gp120) derived from both the macrophage-tropic strain (MN) and the T lymphocyte-tropic strain (IIIB), when added to MDM cultures, enhanced SP mRNA expression. The gp120-induced SP expression was abrogated by pretreating the cells with soluble CD4. Furthermore, the activation of HIV in the latently infected promonocytic cell line (U1) and T-cell line (ACH-2) up-regulated SP mRNA expression. These data support the hypothesis that interaction of HIV and SP may have significant in vivo relevance to the immunopathogenesis of HIV infection and AIDS.

Blood↗
PubMed2002

Alcohol potentiates HIV-1 infection of human blood mononuclear phagocytes.

BACKGROUND: Acute and chronic alcohol abuse impairs various functions of the immune system and thus has been implicated as a cofactor in HIV infection. The mechanisms by which alcohol affects the function of human immune cells that are the targets for HIV are unknown. METHODS: Human blood monocyte-derived macrophages (MDM) were incubated with or without alcohol (10-40 mM) for 24 hr and then infected with HIV for 24 hr. Culture supernatants were harvested for HIV reverse transcription assay. HIV entry receptor (CCR5, CD4, and CXCR4) expression was determined by reverse transcription-polymerase chain reaction and flow cytometry assays. Beta-chemokines were analyzed using enzyme-linked immunosorbent assay. Different HIV strains (Bal, SF-162, 89.6, and UG024) were used for infection experiments. In addition, ADA (macrophage-tropic strain) and murine leukemia virus envelope-pseudotyped HIV infection was carried out. RESULTS: Although alcohol had little effect on HIV T-lymphocyte-tropic strain infection, it significantly enhanced HIV R5 strain infection in MDM. The enhancing effect of alcohol on the HIV R5 strain was further evidenced by the observation that the R5 (ADA) strain envelope-pseudotyped HIV infection is markedly increased by alcohol, whereas murine leukemia virus envelope-pseudotyped HIV infection was not affected. Alcohol significantly up-regulated CCR5 receptor expression and inhibited the endogenous production of beta-chemokines by MDM. CONCLUSION: Alcohol, through the down-regulation of beta-chemokine production and the up-regulation of CCR5 receptor expression, enhances HIV R5 strain infection of MDM and may have an important role as a cofactor in the progression of HIV disease.

Cells, Cultured↗