Biomedical subjects

X He

Publications and source records attributed to X He.

At least 217 records · Page 12Linked to original sources

PubMed1999

Protective alterations in phase 1 and 2 metabolism of aflatoxin B1 by oltipraz in residents of Qidong, People's Republic of China.

BACKGROUND: Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part due to consumption of foods contaminated with aflatoxins, which require metabolic activation to become carcinogenic. In a randomized, placebo-controlled, double-blind phase IIa chemoprevention trial, we tested oltipraz, an antischistosomal drug that has been shown to be a potent and effective inhibitor of aflatoxin-induced hepatocarcinogenesis in animal models. METHODS: In 1995, 234 adults from Qidong were enrolled. Healthy eligible individuals were randomly assigned to receive by mouth 125 mg oltipraz daily, 500 mg oltipraz weekly, or a placebo. Sequential immunoaffinity chromatography and liquid chromatography coupled to mass spectrometry or to fluorescence detection were used to identify and quantify phase 1 and phase 2 metabolites of aflatoxin B1 in the urine of study participants. Reported P values are two-sided. RESULTS: One month of weekly administration of 500 mg oltipraz led to a 51% decrease in median levels of the phase 1 metabolite aflatoxin M1 excreted in urine compared with administration of a placebo (P = .030), but it had no effect on levels of a phase 2 metabolite, aflatoxin-mercapturic acid (P = .871). By contrast, daily intervention with 125 mg oltipraz led to a 2.6-fold increase in median aflatoxin-mercapturic acid excretion (P = .017) but had no effect on excreted aflatoxin M1 levels (P = .682). CONCLUSIONS: Intermittent, high-dose oltipraz inhibited phase 1 activation of aflatoxins, and sustained low-dose oltipraz increased phase 2 conjugation of aflatoxin, yielding higher levels of aflatoxin-mercapturic acid. While both mechanisms can contribute to protection, this study highlights the feasibility of inducing phase 2 enzymes as a chemopreventive strategy in humans.

Acetylcysteine↗

PubMed1999

[Glutathione S-transferase GSTM1 and GSTT1 genotypes and susceptibility to lung cancer].

A 1:1 matched population-based case-control study was conducted in Xuanwei City, Yunnan Province, where the lung cancer mortality is among China's highest. In this study there were 86 newly diagnosed lung cancer cases and 86 matched control subjects with the same sex, fuel type used, and age(+/- 2 years). Buccal cells were collected from each subject to determine the genotypes of GSTM1 and GSTT1. It was found that the rate of GSTM1 null genotype was higher in the case group than in the control group, and its odds ratio was 2.39(95% CI: 1.25-4.56). The odds ratio became 2.62(95% CI: 1.33-5.15) when other possible confounding factors such as smoking, COPD, and the lifetime exposure to unvented fuel combustion (tons) were adjusted. No association was found between GSTT1 null genotype and lung cancer. The rate of GSTM1 null genotype in Xuanwei City was found to be similar to those of other Chinese populations.

Case-Control Studies↗

PubMed1999

Identification and characterization of the molecular lesion causing mucopolysaccharidosis type I in cats.

Mucopolysaccharidosis Type I (MPS I) is the lysosomal storage disease caused by the deficient activity of alpha-L-iduronidase (IDUA). In man, MPS I can occur in severe, mild, or intermediate forms known as the Hurler, Scheie, or Hurler/Scheie syndromes, respectively. MPS I also has been described in cats, dogs, and mice. This manuscript reports the identification and characterization of the mutation causing MPS I in cats. To obtain wild-type feline IDUA cDNAs, two PCR-based strategies were used. PCR primers were constructed from a conserved region of the published human and dog sequences and used to amplify a 224-bp IDUA fragment from normal cat genomic DNA. This fragment was then used to screen a feline uterus cDNA library. PCR also was used to directly amplify IDUA fragments from the same cDNA library. Two overlapping feline IDUA cDNAs encoding 466 amino acid residues of the feline IDUA polypeptide ( approximately 85% of the mature protein based on comparison to the human, dog, and mouse sequences) were obtained by these strategies. To identify the mutation causing MPS I in cats, DNA sequencing was carried out on the corresponding IDUA region from several affected animals. A 3-bp deletion was found on both IDUA alleles in each of the MPS I animals, predicting the deletion of a single aspartate residue from the feline IDUA polypeptide. To confirm the authenticity of this mutation, heteroduplex, SSCP, and transient expression studies were carried out. Over 100 animals from the MPS I colony were screened for the presence of the mutation by heteroduplex and SSCP analyses-in all cases the presence of the 3-bp deletion was 100% concordant with the disease phenotype. For transient expression studies, the two partial, overlapping feline cDNAs were combined and joined in-frame to the 5' end of the canine IDUA cDNA. This wild-type, hybrid cDNA expressed IDUA activity up to sixfold over endogenous levels after transfection into COS-1 cells. A modified full-length IDUA cDNA containing the 3-bp deletion did not express IDUA activity in a transient expression system, providing proof that this lesion was the cause of feline MPS I.

Animals↗

PubMed1999

Comparative study of photophysical properties of isomeric tetrapyridyl- and tetra-(N-hexadecylpyridiniumyl) porphyrins.

Photophysical properties (absorption spectra, fluorescence spectra, lifetimes and quantum yields) were studied for the three isomers of tetrapyridylporphyrins (TPyPs) in CHCl3 and tetra-(N-hexadecylpyridiniumyl) porphyrins (TC16PyPs) in CHCl3, CH3OH and Triton X-100 micelle solution. While the ground-state and excited-state properties are very similar for the three isomers of neutral TPyP, significant differences exist among the isomers of amphiphilic TC16PyP. Amphiphilic porphyrins bearing hydrophilic pyridinium and hydrophobic long-chain alkyl groups are characterized by reduced fluorescence quantum yields, biexponential fluorescence decay, and appreciable aggregation in nonpolar solvents. The observed biexponential fluorescence decay of amphiphilic porphyrins can be interpreted in terms of mixing of the S1 and a close-lying CT state in which an electron is transferred from the porphyrin core to the electron-deficient pyridinium group.

Isomerism↗

PubMed1999

Upstream and downstream sequence elements determine the specificity of the rice tungro bacilliform virus promoter and influence RNA production after transcription initiation.

The contribution of sequences upstream and downstream of the transcription start site to the strength and specificity of the promoter of rice tungro bacilliform virus was analysed in transgenic rice plants. The promoter is strongly stimulated by downstream sequences which include an intron and is active in all vascular and epidermal cells. Expression in the vascular tissue requires a promoter element located between -100 and -164 to which protein(s) from rice nuclear extracts bind. Elimination of this region leads to specificity for the epidermis. Due to the presence of a polyadenylation signal in the intron, short-stop RNA is produced from the promoter in addition to full-length primary transcript and its spliced derivatives. The ratio between short-stop RNA and full-length or spliced RNA is determined by upstream promoter sequences, suggesting the assembly of RNA polymerase complexes with different processivity on this promoter.

Badnavirus↗

PubMed1999

Enhancement of chemotherapy by manipulation of tumour pH.

The extracellular (interstitial) pH (pHe) of solid tumours is significantly more acidic compared to normal tissues. In-vitro, low pH reduces the uptake of weakly basic chemotherapeutic drugs and, hence, reduces their cytotoxicity. This phenomenon has been postulated to contribute to a 'physiological' resistance to weakly basic drugs in vivo. Doxorubicin is a weak base chemotherapeutic agent that is commonly used in combination chemotherapy to clinically treat breast cancers. This report demonstrates that MCF-7 human breast cancer cells in vitro are more susceptible to doxorubicin toxicity at pH 7.4, compared to pH 6.8. Furthermore 31P-magnetic resonance spectroscopy (MRS) has shown that the pHe of MCF-7 human breast cancer xenografts can be effectively and significantly raised with sodium bicarbonate in drinking water. The bicarbonate-induced extracellular alkalinization leads to significant improvements in the therapeutic effectiveness of doxorubicin against MCF-7 xenografts in vivo. Although physiological resistance to weakly basic chemotherapeutics is well-documented in vitro and in theory, these data represent the first in vivo demonstration of this important phenomenon.

Animals↗

PubMed1999

Evaluation of an electronic portal imaging device for transit dosimetry.

The possibility of using a commercially available electronic portal imaging device for transit dosimetry was investigated. The detection unit of the device comprises a metal plate/fluorescence screen and a camera. Basic parameters of this system were investigated: stability, detector uniformity, dose-response curve, field-size dependence and phantom-thickness dependence. It was found that in terms of relative dosimetry, portal images corrected for detector non-uniformity are in good agreement (within 5%) with transit dose distributions measured by film dosimetry. For dose determination, it was found that the use of the device is hampered by an important field-size dependence and phantom-thickness dependence. Both correction factors should be applied if the device is to be used for this purpose.

Absorptiometry, Photon↗

PubMed1999

Comparative tumorigenicity of the cyclopenta-fused polycyclic aromatic hydrocarbons aceanthrylene, dihydroaceanthrylene and acephenanthrylene in preweanling CD-1 and BLU:Ha mouse bioassays.

Cyclopenta-fused polycyclic aromatic hydrocarbons are ubiquitous environmental pollutants and potential human health biohazards. In this study, the tumorigenicity of three single cyclopenta-fused polycyclic aromatic hydrocarbons, aceanthrylene, dihydroaceanthrylene and acephenanthrylene, was examined in preweanling CD-1 and BLU:Ha mouse bioassays at total doses of 175, 437.5 and 875 micrograms/mouse. No death or significant toxicity was observed with the treatment protocol in the tested animals. In CD-1 mice, a significant increase in lung tumor incidence (18-26%, P < 0. 025-0.01) for these three compounds was recorded in animals treated with 875 micrograms as compared with the control animals (3%). Significant numbers of liver tumors (25-41%, P < 0.01-0.001) were induced in all aceanthrylene treatment groups and in animals treated with 875 micrograms acephenanthrylene (35%) at the termination at 9 months. Most liver tumors were induced in male animals. The ED50 values were estimated as 8.5, 10.6 and 12.8 micromol and the TM1.0 were 15.1, 20.4 and 23.1 micromol for aceanthrylene, acephenanthrylene and dihydroaceanthrylene, respectively. In BLU:Ha mice, there was a significant dose-dependent increase in lung tumor incidence, from 4% for the control group to 33% (P < 0.001) for the animals treated with 875 micrograms aceanthrylene and to 24% (P < 0.02) for the animals treated with 437.5 micrograms acephenanthrylene. The ED50 values were 6.0 and 4.4 micromol and the TM1.0 were 9.8 and 6.8 micromol for aceanthrylene and acephenanthrylene, respectively. No significant difference in lung tumor incidence between male and female mice was found. Based on these data and comparisons of tumorigenic potency with other polycyclic aromatic hydrocarbons previously tested in these newborn mouse bioassays, aceanthrylene and acephenanthrylene were classified as weak tumorigens.

Animals↗

PubMed1999

Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection.

To understand the high variability of the asymptomatic interval between primary human immunodeficiency virus type 1 (HIV-1) infection and the development of AIDS, we studied the evolution of the C2-V5 region of the HIV-1 env gene and of T-cell subsets in nine men with a moderate or slow rate of disease progression. They were monitored from the time of seroconversion for a period of 6 to 12 years until the development of advanced disease in seven men. Based on the analysis of viral divergence from the founder strain, viral population diversity within sequential time points, and the outgrowth of viruses capable of utilizing the CXCR4 receptor (X4 viruses), the existence of three distinct phases within the asymptomatic interval is suggested: an early phase of variable duration during which linear increases ( approximately 1% per year) in both divergence and diversity were observed; an intermediate phase lasting an average of 1.8 years, characterized by a continued increase in divergence but with stabilization or decline in diversity; and a late phase characterized by a slowdown or stabilization of divergence and continued stability or decline in diversity. X4 variants emerged around the time of the early- to intermediate-phase transition and then achieved peak representation and began a decline around the transition between the intermediate and late phases. The late-phase transition was also associated with failure of T-cell homeostasis (defined by a downward inflection in CD3(+) T cells) and decline of CD4(+) T cells to </=200 cells/microliter. The strength of these temporal associations between viral divergence and diversity, viral coreceptor specificity, and T-cell homeostasis and subset composition supports the concept that the phases described represent a consistent pattern of viral evolution during the course of HIV-1 infection in moderate progressors. Recognition of this pattern may help explain previous conflicting data on the relationship between viral evolution and disease progression and may provide a useful framework for evaluating immune damage and recovery in untreated and treated HIV-1 infections.

Base Sequence↗

PubMed1999

Construction and in vivo efficacy of a replication-deficient recombinant adenovirus encoding murine growth hormone.

We have constructed a recombinant, replication-deficient, first-generation adenovirus-encoding mouse GH (mGH), AdCMVmGH. This virus directed mGH production from an epithelial cell line in vitro in a dose-dependent manner. When injected into the quadriceps muscle or submandibular ducts of mGH-deficient Snell dwarf mice, AdCMVmGH resulted in the production of significantly elevated serum mGH levels. Furthermore, after i.m. injection, dwarf mice increased in weight by 8% over 4 days and close to 100% by 30 days. When AdCMVmGH was administered to 3- to 4-week-old rats by i.v. injection to assess general metabolic responses, serum mGH, insulin-like growth factor 1, triglycerides and cholesterol levels were significantly elevated. AdCMVmGH should be a valuable experimental tool for the controlled, directed expression of mGH in preclinical mouse model studies.

Adenoviridae↗

PubMed1999

[Anatomical study of the thyroid foramen in human larynx: a study of 100 dissections].

The foramen thyroideum was systematically studied on the specimen of larynx of 50 fresh corpses. Among the one hundred dissections performed, the foramen thyroideum was noted only in one specimen (2 foramen). It was symmetrical not only in the position but also in the diameter. In both of these cases, the foramen thyroideum always contains few vessels and nerves. It's possible physiological role and the origin of the contents of the foramen thyroideum are discussed based on the research literature.

Adolescent↗

PubMed1999

Studies of molecular pharmacophore/receptor models for GABAA/BzR subtypes: binding affinities of symmetrically substituted pyrazolo[4,3-c]quinolin-3-ones at recombinant alpha x beta 3 gamma 2 subtypes and quantitative structure-activity relationship studies via a comparative molecular field analysis.

A series of symmetrically substituted pyrazoloquinolinones was synthesized to probe the BzR binding site of different GABAA/Bz receptor subtypes. The affinities of the ligands for different BzR subtypes have been determined by radioligand binding assays on 5 distinct recombinant GABAA receptor isoforms [alpha x beta 3 gamma 2 (x = 1,2,3,5, or 6)]. Most of the ligands synthesized exhibited potent biological activity in vitro. Among them, 3 ligands exhibited enhanced affinity for the alpha 2 beta 3 gamma 2 subtype in comparison to the other subtypes, six ligands demonstrated higher affinity for the alpha 3 beta 3 gamma 2 subtype, while 2 ligands showed some enhanced affinity for the alpha 5 beta 3 gamma 2 subtype. The remainder of the ligands exhibited relatively higher affinities at the alpha 1 containing subtype. To map out the steric and electronic differences between the benzodiazepine binding subtypes, a QSAR analysis by the method of Comparative Molecular Field Analysis (CoMFA) of each receptor subtypes was carried out.

Binding Sites↗

PubMed1999

Construction of high ergosterol-producing yeast strains and study on the optimal conditions for culture.

High ergosterol-producing yeast strains were constructed by primary screening isolation of haploid mutagenesis and protoplasts fusion. The fermentation conditions of fused strain YEF-21 were studied. Under the optimal conditions, i.e., the medium for fermentation consisted of 8% glucose 1% polypeptone 1% yeast extract; initial pH nature; 60 mL broth/250 mL flask; inoculum volume 10%; fermentation time 30 hours at 28 degrees C and 200 r/min; the comprehensive value of biomass and ergosterol content of YEF-21 is 1.54 and 1.55 times that of the parent strains YE227 and YE180, respectively. The fused strain YEF-21 is stable enough genetically according to the analysis of genetic stability, and it is a high ergosterol-producing strain that has prospect for application.

Culture Media↗

PubMed1999

Effects of the configuration of a multi-epitope chimeric malaria DNA vaccine on its antigenicity to mice.

OBJECTIVE: Four B and Th cell epitopes were selected from conservative domain of Plasmodium falciparum antigens to construct two groups of chimeric malaria DNA vaccines with different configurations and their antigenicities were studied. METHODS: The partially synthesized oligonucleotide was annealed, PCR amplified and cloned into a mammalian cell expression vector. By using a pair of isocaudamers on the vector, different single copies of B epitopes were multiplied and were tenderly stringed into two groups of chimeric DNA vaccine with different configurations. BALB/c mice were immunized with these DNA plasmids by either intramuscular or intradermal injections. RESULTS: The antisera from the immunized mice tested by ELISA showed that only the configuration which had a single copy of universal T helper cell epitope, CS. T3, located at the C terminal of the multi-copy B cell epitopes induced a high antibody response. The T helper cell epitope at any other position of the peptide, or the double T helper cell epitopes configured with the B cell epitopes did not enhance antibody response, and some configurations even decreased the humoral response to a B cell epitope. CONCLUSION: This study demonstrated that both combination and configuration of the epitope may affect the antigenicity of a chimeric multiple antigen.

Animals↗

PubMed1999

Molecular mechanisms of drug resistance in Mycobacterium tuberculosis clinical isolates.

OBJECTIVE: To study the molecular mechanisms of drug resistance in Mycobacterium (M). tuberculosis, to evaluate the value of the beta subunit of RNA polymerase (rpoB), the ribosomal siz protein (rpsL), 16Sr RNA (rrs), catalase-peroxidase gene (katG) genes, and inhA regulatory sequence as genetic markers for rifampin (RFP), streptomycin (SM), isoniazid (INH) resistance, and to develop new methods for detecting the drug resistance. METHOD: The rpoB, rpsL, rrs, katG genes, and inhA regulatory sequence in 85 M. tuberculosis isolates were analyzed with polymerase chain reaction (PCR), PCR-single-stranded conformation polymorphism analyses (SSCP), PCR-nucleotide sequence analyses (NS) and PCR-restriction fragment length polymorphism (RFLP). RESULTS: The sensitivity of amplifying the drug-resistant genes with PCR was 1-10 pg DNA. Twenty-eight drug-sensitive strains had no alterations in the rpoB, rpsL, rrs, katG genes, and inhA regulatory sequences. 93.3% of 45 M. tuberculosis RFP-resistant (RFPr) isolates had rpoB mutations. Codon 531 and 526 of the rpoB are the most common sites of nucleotide substitutions. 72.5% of 40 SM-resistant (SMr) isolates had an identical mutation at codon 43 of the rpsL gene. No isolates had a mutation at codon 88 of the rpsL. Only 7.5% of these SMr isolates had A-to-C transversions at position 513 of the rrs gene. Of 34 INH-resistant (INHr) isolates, 11.8% had complete katG deletions, 55.9% had mutations in the selected region of katG. Only 8.8% had alterations in the inhA regulatory sequences. 60.9% of RFPr, INHr, and SMr isolates had mutations in genetic markers for these drug resistance. CONCLUSIONS: Most drug resistance in M. tuberculosis was due to simple mutations occurring in chromosomally encoded genes. Alterations in rpoB, rpsL and katG gene may be the important mechanism of M. tuberculosis resistance to RFP, SM, and INH. PCR, PCR-SSCP, PCR-NS, and PCR-RFLP are going to become the simple, rapid and reliable diagnostic tests for drug resistance in M. tuberculosis.

Antitubercular Agents↗

PubMed1999

[Development of the diagnosis and treatment of glaucoma in China].

Diagnosis and treatment of glaucoma is one of the greatest achievements in the development ophthalmology. The process of achieving is also a very inspiring chapter in its history. As histories of other sciences, the development of diagnosis and treatment of glaucoma is achieved through the following process: After accumulation for many years, then it entered the stage of explaining the phenomenon with the development of other sciences. Finally, its situation is determined by experiment and being widely applied in clinical practice. Meanwhile, there is no end for the findings of new diagnostic and therapeutic methods. More achievements will surely be made for developments in relevant sciences and increasing needs in clinical practice.

China↗

PubMed1999

[Clinical analysis of 935 cases of non-Hodgkin's lymphoma].

OBJECTIVE: To analyze the results of treatment of non-Hodgkin's lymphoma (NHL). METHODS: The results of treatment in 935 NHL patients were reviewed according to life table Log rank analysis. RESULTS: Patients with moderately malignant NHL had better long-term survival, as compared with other pathologic types (P < 0.05). Patients in clinical stage I had better prognosis than those in stage II, III and IV (P < 0.001). Patients achieved CR as short-term response had the best prognosis. When analyzed according to treatment modalities, the long-term effect was seemingly better in patients treated with chemotherapy + radiotherapy than in patients treated with radiotherapy alone or chemotherapy alone, but the different was statistically insignificant. If the results are compared between patients treated in 1983 through 1988 and those in 1989 through 1993, there was marked improvement in long-term survival in the latter time period during which patients were given more intensive chemotherapy. CONCLUSION: The long-term survival rate of patients with NHL was closely related to pathologic types, clinical stage, short-term therapeutic effect. Intensive chemotherapy help improve prognosis. The leaping manner of NHL dissemination requires sufficient systematic therapy.

Adolescent↗

PubMed1999

[Histocytopathological study on gastric mucosa of spleen deficiency syndrome].

OBJECTIVE: To explore the pictures of gastric mucosa of Spleen deficiency syndrome, and the relationship between the degree of pathological changes of gastric mucosa and types of Spleen deficiency syndrome. METHODS: One hundred and eighty-eight Spleen deficiency patients with organic diseases of heart, lung, liver, gallbladder, pancreas, intestine and kidney excluded were examined their gastric mucosa. Tests of histopathology and subcellular ultrastructure were conducted by using optical microscope, electron scanning microscope, electron transmission microscope and histochemical staining methods. RESULTS: The gastric mucosa of Spleen Qi deficiency and Spleen Yang deficiency patients could either be affected with organic lesion (type G) or unaffected (type F); the gastric mucosa of Spleen Yin deficiency and Spleen deficiency with Qi stagnation were both affected by gastric lesions, and the degree of their lesions was more serious than that of Spleen Qi deficiency of type G and Spleen Yang deficiency of type G, P < 0.05-0.01. CONCLUSION: Pathological changes did not necessarily occur in the gastric mucosa of Spleen deficiency patients; the degree of pathological changes was relevant with the evolution of Spleen deficiency types.

Adult↗