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Biomedical subjects

S Cao

Publications and source records attributed to S Cao.

At least 37 records · Page 2Linked to original sources

Synergistic antitumor activity of irinotecan in combination with 5-fluorouracil in rats bearing advanced colorectal cancer: role of drug sequence and dose.

The basis for current clinical trials in the treatment of colorectal cancer with the combination of irinotecan (CPT-11) and 5-fluorouracil (FUra) with or without leucovorin (LV) is their proven activity as single agents, their different mechanisms of action, and lack of CPT-11 cross-resistance to previous FUra/LV treatment. The role of drug dose and administration sequence in this combination was studied in vivo using a rat colon tumor model (Ward colon carcinoma); we administered CPT-11 and FUra by i.v. push once a week for four consecutive weeks (weekly x 4), a clinically relevant schedule. The maximum tolerated doses (MTDs) of CPT-11 and FUra administered as single agents were 100 mg/kg/week for both agents. Three different combination administration sequences were evaluated: (a) CPT-11 administered simultaneously with FUra (sequence I); (b) FUra administered 24 h before CPT-11 (sequence II); and (c) CPT-11 administered 24 h before FUra (sequence III). When combining the two drugs at 50% of their respective MTD, the antitumor efficacy was sequence dependent with 62, 38, and 95% complete tumor regression rate for sequences I, II, and III, respectively. For sequences I and II, dose escalation to 75% of the MTD for each drug was paralleled by reversible host toxicity with no significant increase in the antitumor activity of the combination. With sequence III, however, the combination was lethal in 100% of treated animals when the doses of both drugs were at 75% of the MTD or higher. With the sequential combination of CPT-11 followed 24 h later by FUra (sequence III), the high complete tumor regression rate (cure) could be maintained, even when the dose of CPT-11 was reduced to 12.5% of the MTD as long as the doses of FUra was kept at 50 -75 % of the MTD. The data demonstrate that the antitumor activity and toxicity of combining CPT-11 with FUra is highly sequence dependent and that a sequence of CPT-11 preceding FUra is superior with a significant increase in the therapeutic index over the other sequences tested. In addition, the data also demonstrate that toxicity associated with high dose of CPT-11 can be eliminated without loss of the antitumor efficacy by reducing the dose of CPT-11 to at least 50% of its MTD, whereas the dose of FUra is kept at 50-75 % of its MTD.

Animals↗

Production, properties and application to nonaqueous enzymatic catalysis of lipase from a newly isolated Pseudomonas strain.

A potent bacterium for lipase production was isolated from soil and identified as Pseudomonas species. It produced lipase constitutively. A mutant of this strain with a lipase productivity 3.25-fold higher was obtained by treatment with ultraviolet (UV) and nitrosoguanidine (NTG). Its fermentation condition was optimized to a lipase yield of 87.5 U/ml. The lipase had maximum activity at pH 9.0 and 45 degrees C. It was stable at pHs from 7.0 to 11.0 and below 60 degrees C. The effects of metal ions, surfactants and bile salts were also studied. The lipase was 1,3-specific. In organic solvents, the thermal stability of the lipase was significantly enhanced. Its optimum temperature was also slightly increased. The optimum water activity was found between 0.5 and 0.6. The lipase was successfully applied in organic phase to catalyze the glycerolysis of palm oil for monoglyceride (MG) production, and the enantioselective esterification of (R,S)-2-octanol. The enantioselectivity of the lipase could be enhanced substantially by treatment with an amphipathic.

Journal Article↗

Contribution of caveolin protein abundance to augmented nitric oxide signaling in conscious dogs with pacing-induced heart failure.

Myocardial NO signaling appears elevated in heart failure (HF). Whether this results from increased NO production, induction of the high-output NO synthase (NOS)2 isoform, or changes in NOS regulatory pathways (such as caveolae) remains controversial. We tested the hypothesis that increased abundance of caveolin-3 and/or sarcolemmal caveolae contribute to increased NO signaling in pacing-induced HF. Abundance of caveolin-3 (0.59+/-0.08 versus 0.29+/-0.08 arbitrary units, P = 0.01) but not caveolin-1 was increased in HF compared with control conditions, assessed by Western blot. Additionally, transmission electron microscopy revealed increased caveolae (2. 7+/-0.4 versus 1.3+/-0.3 per micrometer myocyte membrane, P<0.005). The association between caveolin-3 and NOS3 at the sarcolemma and T tubules was unchanged in HF compared with control myocytes. The impact of NOS inhibition with L-N(G)-methylarginine hydrochloride (L-NMMA) on beta-adrenergic inotropy was assessed in conscious dogs before and after HF. In control dogs, dobutamine (5 microg. kg(-1) x min(-1)) increased +dP/dt by 36+/-7%, and this was augmented to 66+/-24% by 20 mg/kg L-NMMA (P = 0.04 versus without L-NMMA, n = 8) but not affected by 10 mg/kg L-NMMA (34+/-10%, P = NS; n = 8). In HF, dobutamine +dP/dt response was depressed (P<0.001 versus control), and increased concentrations were required to match control inotropic responses (10 to 15 microg. kg(-1) x min(-1), 48+/-7%). L-NMMA enhanced +dP/dt responses similarly at 10 mg/kg (61+/-17%, P = 0.02; n = 4) and 20 mg/kg (54+/-7%, P = 0.04; n = 7). Caveolin-3 abundance positively correlated with L-NMMA augmentation of dobutamine inotropic responses in HF (r = 0.9, P = 0.03; n = 4). Thus, in canine pacing-induced HF, expression of caveolin-3 and of sarcolemmal caveolae is increased. This increase is associated with augmented agonist-stimulated NO signaling, likely via a compartmentation effect.

Animals↗

alpha-fluoro-beta-alanine: effects on the antitumor activity and toxicity of 5-fluorouracil.

We have shown previously that (R)-5-fluoro-5,6-dihydrouracil (FUraH(2)) attenuates the antitumor activity of 5-fluorouracil (FUra) in rats bearing advanced colorectal carcinoma. Presently, we found that alpha-fluoro-beta-alanine (FBAL), the predominant catabolite of FUra that is formed rapidly via FUraH(2), also decreased the antitumor activity and potentiated the toxicity of FUra. In rats treated with Eniluracil (5-ethynyluracil, GW776), excess FBAL, in a 9:1 ratio to FUra, produced similar effects when administered 1 hr before, simultaneously with, or 2 hr after FUra. FBAL also decreased the antitumor activity of FUra in Eniluracil-treated mice bearing MOPC-315 myeloma at a 9:1 ratio with FUra, but not at a 2:1 ratio. FBAL did not affect the antitumor activity of FUra in mice bearing Colon 38 tumors. We also evaluated the effect of thymidylate synthase (TS) and thymidine kinase (TK) from tumor extracts after FUra +/- Eniluracil +/- FBAL treatment. The activity of TK was similar among the three groups at both 18 and 120 hr. There was also no difference in TS inhibition ( approximately 35%) at 18 hr. However, significantly more TS inhibition was observed in the Eniluracil/FUra group than in the FUra-alone group at 120 hr. FBAL did not alter the effect of Eniluracil/FUra in TS inhibition. Neither FUraH(2) nor FBAL affected the IC(50) of FUra in culture. Thus, the effect of FBAL did not result from direct competition with FUra uptake or immediate anabolism. Either another downstream catabolite that is not formed in cell culture is the active agent, or the effect requires the complexity of a living organism or an established tumor.

Animals↗

Mechanism of action of the dual topoisomerase-I and -II inhibitor TAS-103 and activity against (multi)drug resistant cells.

UNLABELLED: TAS-103 is a recently developed dual inhibitor of topoisomerase-I (topo-I) and topoisomerase-II (topoII). TAS-103 has documented cytotoxicity in vitro and antitumor activity against a variety of mouse, rat, and human xenografts in vivo. PURPOSE: To determine TAS-103 activity against (multi)drug resistant cells in vitro and to delineate its mechanism of action. METHODS: TAS-103 was evaluated for activity against three human multidrug-resistant cell lines representing resistance mediated by P-glycoprotein (Pgp)-, multidrug resistance protein (MRP), and lung resistance protein (LRP) as well as one camptothecin-resistant cell line associated with a mutated topo-I enzyme. Drug sensitivity following short (2 h), intermediate (6-8 h) and long term (24 h) exposures were compared. The mechanism of action was studied by evaluating inhibition of topoisomerase-I and -II specific DNA relaxation assays, drug-induced DNA/protein cross-link formation, and competitive DNA intercalation with ethidium bromide. RESULTS: Increasing the exposure time only modestly potentiated TAS-103 cytotoxicity (3-5 fold) demonstrating a lack of strong exposure duration dependency. TAS-103 cytotoxicity was not affected by the presence of any of the drug resistance mechanisms studied. TAS-103 inhibits topo-I and -II activity in DNA relaxation assays, but in our assay system TAS-103 was found to have only a weak ability to induce DNA-protein crosslinks. DNA migration patterns in agarose gel electrophoresis indicate that TAS-103 can interact directly with DNA. Also its ability to displace ethidium bromide which has intercalated into the DNA provides an indication on the nature of drug-DNA interaction. CONCLUSIONS: TAS-103 cytotoxicity is not affected by the presence of Pgp, MRP, LRP or mutations in the CAM binding region of the topo-I enzyme and its growth-inhibitory effect appears to be weakly dependent on exposure duration. The presented evidence suggest that the inhibitory effects of TAS-103 on topo-I and -II may in part be related to its DNA binding rather than primarily through stabilization of topo-I or -II intermediates with DNA through specific binding to the enzymes.

Aminoquinolines↗

Preclinical development of eniluracil: enhancing the therapeutic index and dosing convenience of 5-fluorouracil.

Eniluracil (5-ethynyluracil, GW 776, 776C85) is being developed as a novel modulator of 5-fluorouracil (5-FU) for the treatment of cancer. Eniluracil is an effective mechanism-based inactivator of dihydropyrimidine dehydrogenase (DPD), the first enzyme in the catabolic pathway of 5-FU. By temporarily eliminating this prevalent enzyme, eniluracil provides predictable dosing of 5-FU and enables oral administration of 5-FU to replace intravenous bolus and continuously infused dosing. New DPD is synthesized with a half-life of 2.6 days. It also eliminates the formation of problematic 5-FU catabolites. Most importantly, in laboratory animals, eniluracil increases the therapeutic index and absolute efficacy of 5-FU. Accompanying reports in this journal indicate that eniluracil has promising clinical potential.

Administration, Oral↗

Up-regulation of base excision repair activity for 8-hydroxy-2'-deoxyguanosine in the mouse brain after forebrain ischemia-reperfusion.

The repair enzyme 8-oxoguanine glycosylase/ apyrimidinic/apurinic lyase (OGG) removes 8-hydroxy-2'deoxyguanosine (oh8dG) in human cells. Our goal was to examine oh8dG-removing activity in the cell nuclei of male C57BL/6 mouse brains treated with either forebrain ischemia-reperfusion (FblR) or sham operations. We found that the OGG activity in nuclear extracts, under the condition in which other nucleases did not destroy the oligodeoxynucleotide duplex, excised oh8dG with the greatest efficiency on the oligodeoxynucleotide duplex containing oh8dG/dC and with less efficiency on the heteroduplex containing oh8dG/dT, oh8dG/dG, or oh8dG/dA. This specificity was the same as for the recombinant type 1 OGG (OGG1) of humans. We observed that the OGG1 peptide and its activity in the mouse brain were significantly increased after 90 min of ischemia and 20-30 min of reperfusion. The increase in the protein level and in the activity of brain OGG1 correlated positively with the elevation of FblR-induced DNA lesions in an indicator gene (the c-fos gene) of the brain. The data suggest a possibility that the OGG1 protein may excise oh8dG in the mouse brain and that the activity of OGG1 may have a functional role in reducing oxidative gene damage in the brain after FblR.

8-Hydroxy-2'-Deoxyguanosine↗

Small-diameter portacaval H-graft shunt: a paradigm shift back to surgical shunting in the management of variceal bleeding in patients with preserved liver function.

Small-diameter portacaval H-graft (SDPHG) shunts are partial portosystemic shunts that control variceal bleeding while preserving nutrient blood flow to the liver, minimizing postoperative encephalopathy and liver failure. Since July 1, 1997, we placed SDPHG shunts in 18 patients (age, 52.1 +/- 2.6 years; range, 35 to 72 years) with cirrhosis (Child's class A, B, and C in 6, 10, and 2 patients, respectively) and refractory variceal bleeding who were not candidates for transplantation. Ten procedures (55.6%) were urgent or emergent. SDPHG shunts effectively reduced the portacaval pressure gradient (18 +/- 3 v 5 +/- 2 mm Hg; P <.05). Surgical times (210 +/- 11 minutes), estimated blood losses (358.3 +/- 107.8 mL), transfusion requirements (0 transfusions in 10 patients; 55.6%; mean, 0.9 +/- 0.3 units), and postoperative hospitalization (7.7 +/- 1.0 days) were excellent. Surgical mortality (30 days) was 0%. During 14. 0 +/- 1.9 months (range, 1.1 to 29.1 months) of follow-up, 4 patients (22.2%) died, including both patients with Child's class C cirrhosis. The cumulative 1-year survival rate was 82.1% (Child's class A, B, and C, 83.3%, 90%, and 0%, respectively). Long-term survivors had significantly lower preoperative Child-Pugh scores compared with nonsurvivors (7.8 +/- 0.3 v 9.5 +/- 1.0; P <.05). Postoperative encephalopathy developed in 3 survivors (20%). Fifteen patients (83.3%) have not experienced rebleeding; shunt failure led to rebleeding in only 1 patient (5.6%). SDPHG shunt placement can be performed with low morbidity and surgical mortality. Nontransplantation candidates with Child's class A and B cirrhosis have excellent long-term survival with this safe, effective, and definitive treatment for refractory variceal bleeding.

Adult↗

Gene transfer of recombinant endothelial nitric oxide synthase to liver in vivo and in vitro.

Endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) contributes to hepatic vascular homeostasis. The aim of this study was to examine whether delivery of an adenoviral vector encoding eNOS gene to liver affects vasomotor function in vivo and the mechanism of NO production in vitro. Rats were administered adenoviruses encoding beta-galactosidase (AdCMVLacZ) or eNOS (AdCMVeNOS) via tail vein injection and studied 1 wk later. In animals transduced with AdCMVLacZ, beta-galactosidase activity was increased in the liver, most prominently in hepatocytes. In AdCMVeNOS-transduced animals, eNOS protein levels and catalytic activity were significantly increased. Overexpression of eNOS diminished baseline perfusion pressure and constriction in response to the alpha(1)-agonist methoxamine in the perfused liver. Transduction of cultured hepatocytes with AdCMVeNOS resulted in the targeting of recombinant eNOS to a perinuclear distribution and binding with the NOS-activating protein heat shock protein 90. These events were associated with increased ionomycin-stimulated NO release. In summary, this is the first study to demonstrate successful delivery of the recombinant eNOS gene to liver in vivo and in vitro with ensuing NO production.

Adenoviridae↗

T cell immunity in neonates.

Typically, neonates exhibit decreased or aberrant cellular immune responses when compared to adults, resulting in increased susceptibility to infection. However, it is clear that newborns are able to generate adult-like protective T cell responses under certain conditions. The focus of our research is to understand the deficiencies within the neonatal immune system that lead to improper cellular responses and how priming conditions can be altered to elicit the appropriate T cell response necessary to protect against development of pathogen-induced disease. With these goals in mind, we are exploring the attributes of neonatal T cells and their development, as well as the conditions during priming that influence the resulting response to immune challenge during the neonatal period.

Age Factors↗

Overexpression of Bax enhances antitumor activity of chemotherapeutic agents in human head and neck squamous cell carcinoma.

Overexpression of the Bax protein in human head and neck squamous cell carcinoma A253 cells was reported to result in an increased sensitivity to various chemotherapeutic agents in vitro (Guo et al., Oncol. Res., 11: 91-99, 1999). In the present study, the relationship between Bax expression and response to chemotherapy was further investigated in vitro and in vivo model systems. For in vitro study, A253, A253/Vec (pcDNA3 vector transfectant), and A253/Bax (pcDNA3/Bax transfectant, expressing 50-fold higher Bax protein than A253 and A253/Vec) cells were exposed to various concentrations of raltitrexed (a specific thymidylate synthase inhibitor) and SN-38 (a topoisomerase I inhibitor) for 2 h, and cell growth inhibition was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide clonogenic assay. Compared to A253/Vec, A253/Bax cells exhibited 9.5- and 13.5-fold increases in sensitivity to raltitrexed and SN-38, respectively. For in vivo study, A253/Vec and A253/Bax tumor xenografts were established by s.c. injection of tumor cells into nude mice. The antitumor activity and toxicity of raltitrexed (i.v. push daily for 5 days) and irinotecan (a prodrug of SN-38; i.v. push daily for 3 days) were evaluated. The maximum tolerated doses of raltitrexed and irinotecan were 30 and 100 mg/kg/day, respectively. At the maximum tolerated doses, minimal antitumor activity was observed with raltitrexed, although irinotecan was more active than raltitrexed against A253 or A253/Vec tumors. In contrast, both raltitrexed and irinotecan were significantly more active against A253/Bax xenografts than against A253/Vec xenografts; the yield for complete tumor regression (cure) was 40% and 100% with raltitrexed and irinotecan, respectively, with no significant toxicity. Furthermore, the observed increase of antitumor activity in A253/Bax tumors was associated with an enhanced induction of apoptosis in vivo. The in vivo results demonstrated a proof of the principal concept that selecting up-regulation of the proapoptosis gene Bax can provide the basis for a greater therapeutic efficacy to a variety of chemotherapeutic agents with different structures and mechanisms of action.

Animals↗

[Studies on schedules for human rabies immunization].

OBJECTIVES: To study the feasibility of interferon (INF) plus an immunization schedule of two dose-two dose-one dose (2 - 2 - 1) of rabies vaccine and a simple 2 - 2 - 1 schedule, and to explore immune regulation mechanism of INF. METHODS: For an IFN plus 2 - 2 - 1 schedule, 5.0, 5.0 and 2.5 I.U. of primary hamster kidney cell rabies vaccine (PHKCV) were injected on the 1st, 7th and 14th day, respectively, and 0.2 million I.U. of IFN-alpha on the 1st day simultaneously. For a simple 2 - 2 - 1 schedule, only 5.0, 5.0 and 2.5 I.U. PHKCV were injected on the 1st, 7th and 14th day, respectively. And, for controls, a routine schedule recommended by WHO was used. RESULTS: On the 7th day after immunization, their geometric mean titer (GMT) of antibody was 1.71, 1.57 and 1.21 for the above three schedule groups, respectively; on the 14th day, 62.77, 58.79 and 28.96; on the 45th day, 76.64, 72.90 and 62.22. Conversion rate of antibody was 85.00%, 61.11% and 65.00%, respectively on the 7th day, and was 100.00% for all on the 14th day. Proportion of those with protective antibody level was 10.00%, 0.00% and 0.00%, respectively for the three schedule groups, on the 7th day; 100.00%, 100.00% and 95.00%, on the 14th day; and was 100.00% for all on the 45th day. Proportion of those with antibody titer more than 1:1 was 55.00%, 33.33% and 20.00%, respectively, on the 7th day. Adverse reaction rate was 0.00% - 55.00%, without significant difference between three schedule groups. CONCLUSIONS: Lower dose of IFN could enhance the effect of immune response to rabies vaccine. IFN plus 2 - 2 - 1 rabies vaccine schedule was better than that of simple 2 - 2 - 1 schedule, while the later was better than the routine schedule.

Adolescent↗

[Malignant transformation of mouse embryonic fibroblast induced by mitochondrial DNA fragments].

OBJECTIVE: To investigate the malignant transforming effect and mechanism of mitochondrial DNA (mtDNA) fragments. METHODS: Tumorigenicity of mtDNA-transformed mouse embryonic fibroblast (NIH3T3) in nude mice was studied using transgenic techniques. Transformed tumors were detected by pathological examination and hybridization signals of mtDNA probe were analyzed by fluorescence in situ hybridization (FISH) techniques. RESULTS: Hybridization signals were observed on the nuclei of 18% - 20% NIH 3T3 cells 1 week after mtDNA fragments transforming. Tumor from mtDNA-transformed NIH 3T3 cells was developed in all 8 nude mice (8/8) respectively 2 weeks after the transformation. The pathological characteristics of the tumors developed were similar to that of fibrosarcoma. CONCLUSIONS: Auto-integration of mtDNA fragments into nuclear genome is a new factor involved in carcinogenesis.

Animals↗

[Matrix effects in inductively coupled plasma mass spectrometry by use of organic solvents].

Matrix effects arising from ethanol, propanol, glycerol, acetic acid, ethylenediamine and triethanolamine in inductively coupled plasma mass spectrometry have been studied. Addition of ethanol, propanol, glycerol, acetic acid, ethylenediamine and triethanolamine into solution has an enhancement effect on the signal intensity of analyte with ionization potential between 9 and 11 eV. The ethylenediamine and triethanolamine have higher enhancement effect on the signal intensity of Hg than that of ethanol, propanol, glycerol and acetic acid. Addition of ethylenediamine and triethanolamine into solution has a suppression effect on the signal intensity of Pb and Sr. The mechanism of the enhancement or suppression was investigated. The signal enhancement of Hg in the presence of ethylenediamine and triethanolamine is not caused by improved degree of ionization of Hg and nebulization efficiency. The suppression effects of Pb and Sr in the presence of ethylenediamine and triethanolamine are due to decrease of atomization efficiency of these elements. A method for the determination of Hg in the biological standard samples by ICP-MS was developed.

1-Propanol↗

[Determination of ultra-trace rare-earth elements in human plasma by inductively coupled plasma mass spectrometry].

Inductively coupled plasma mass spectrometry (ICP-MS), highly sensitive inorgnic analytic technique, fits to determine ultra-trace rare-earth elements in human plasma. Under the optimized conditions detection limits for 15 rare-earth elements are in the range of 0.7 (for Eu)-5.4 (for Gd) ng.L-1. Indium as an internal standard element is used to compensate for matrix suppression effect and sensitivity drift. Three kinds of preparation methods, diluted with 1% HNO3, digested with HNO3-H2O2 and with HNO3-HClO4, are checked and compared, and the former is the simplest way to be measured. The samples diluted with 1% HNO3, stored in 4 degrees C, are very steady for 16 days. With the method, 11 healthy plasma samples in Changchun area of China are analysed.

Europium↗

Involvement of cyclin D1-cdk5 overexpression and MCM3 cleavage in bax-associated spontaneous apoptosis and differentiation in an A253 human head and neck carcinoma xenograft model.

Time-dependent ladder-type DNA fragmentation and morphological alterations consistent with apoptosis were observed among A253 human head and neck squamous cell carcinoma (HNSCC) cells in nude mice from 15 to 18 days after transplantation, without any drug treatment. No evidence of ladder-type DNA fragmentation was detected in A253 cells in vitro or in normal nude mouse tissues (skin and muscle). Our aim was to explore molecular factors associated with such spontaneous apoptosis. Bcl-2 protein expression decreased, while bax protein expression increased from day 9 after transplantation. Moreover, altered expression of bcl-2 and bax was accompanied by the increased proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). Time-dependent dephosphorylation of Rb, followed by proteolytic cleavage, was also observed from day 9 after transplantation. The data indicate that the caspase-3 activation and cleavage of Rb protein may represent important steps in the regulation pathway of bax-mediated spontaneous apoptosis. Interestingly, the time-dependent activation of spontaneous apoptosis was almost simultaneous with the induction of differentiation and increased expression of several differentiation-associated regulatory proteins. An increased expression of cyclin D1 and cyclin-dependent kinase-5 (cdk5) was observed from day 9 after transplantation, whereas only slight alteration of cdk4 expression was found. The time-dependent activation of cyclin D1 and cdk5 preceded both the induction of ladder-type DNA fragmentation and increased keratin pearl formation. Furthermore, MCM3 was cleaved early in spontaneous apoptosis and differentiation. Our observations suggest the involvement of cyclin D1-cdk5 overexpression and MCM3 cleavage in bax-mediated spontaneous apoptosis and differentiation in A253 xenografts. P53 and WAF1 proteins were not expressed in the xenografts, indicating that the changes in the regulatory proteins during apoptosis and differentiation were not p53 or WAF1 dependent.

Animals↗

[Effects of strontium in drinking water on the growth of school-age children].

An epidemiological study on the effect of strontium in drinking water on body shape development, bone age, prevalence of caries and dental fluorosis was carried out. The results show: there is a certain promotion on the development of bone age of school-age children, especially of girls, and there is no obvious impact on body shape developing when the concentration of strontium in drinking water is only 10 mg/L. The correlation between strontium in drinking water and the prevalence of caries in children could not get a conclusive evidence in this paper. A further epidemiological investigation is necessary if the role of strontium against caries should be proved.

Adolescent↗

[Study on transient infection of T cell lines by M tropic HIV-1 strains].

OBJECTIVE: To reveal the mechanism of transient infection of T cell by HIV-1 isolates of early stages from Yunnan and Xinjiang, China. METHODS: We made these viruses pass on CXCR4 expressing T cell lines and CCR5 expressing U937 cell line. After having observed the biological phenotype, we analyzed sequences of env gene to find genetic mutations of the strains, and used heteroduplex mobility assay (HMA) to show the complexity of the virus groups. RESULTS: Sequence analysis indicated that these viruses are M tropic, NSI strains, correlating with their phenotype; they mutated largely through T cell passage, all showed sequence characteristics deviating from M tropic/NSI to different extents. HMA results indicated the complexity of virus groups was low at the very beginning of the passage and kept high later. CONCLUSION: We concluded that these viruses tried mutating to different directions to adapt the T cell line but all failed. Although env gene correlates with cell tropism, coreceptor usage and HIV syncytium inducing, it may have relationship with the whole genome, whether these phenotypes are present or not. The results imply that there is no T tropic/SI strain in the M topic/NSI virus pool in early infection, it is generated later following continued infection in vivo.

Amino Acid Sequence↗