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Biomedical subjects

Q Yang

Publications and source records attributed to Q Yang.

At least 181 records · Page 10Linked to original sources
PubMed2000

Effects of peroxisome proliferators on the thymus and spleen of mice.

The effects of peroxisome proliferators on the immune system of male C57B1/6 mice have been investigated. Significant atrophy of the thymus and spleen was observed in animals treated with potent peroxisome proliferators (e.g. perfluorooctanoic acid (PFOA), di(2-ethylhexyl)phthalate (DEHP), Wy-14643 and nafenopin), whereas the effects of a moderate peroxisome proliferator (i.e. acetylsalicylic acid (ASA)) were relatively weak. The time course of thymic and splenic atrophy caused by PFOA was found to resemble the time course of the increase in liver weight and of peroxisome proliferation. Analysis of the numbers and phenotypes of thymocytes and splenocytes from PFOA-treated mice revealed the following: (i) the numbers of thymocytes and splenocytes were decreased > 90% and about 50%, respectively, by PFOA treatment; (ii) although all populations of thymocytes were decreased, the immature CD4+CD8+ population was decreased most dramatically; (iii) the numbers of both T and B cells in the spleen were decreased by PFOA treatment. Analysis of the cell cycle of thymocytes indicated that the thymic atrophy caused by PFOA in mice results, at least in part, from inhibition of thymocyte proliferation. Interestingly, in vitro exposure to PFOA for up to 24 h did not produce analogous effects in either thymocytes or splenocytes. Thus, the thymic and splenic atrophy caused by PFOA appears to involve an indirect pathway.

Animals↗
PubMed2000

Tris lipidation: a chemically flexible technology for modifying the delivery of drugs and genes.

1. One of the major challenges in the development of pharmaceuticals is their formulation with other materials to give them the desired bioavailability profile when administered into the body. 2. We have developed a flexible platform technology (Tris lipidation) to simply and effectively alter the lipophilicity of drugs. As implied by the name, the technology uses the common buffer Tris as a linker between the drugs of interest and a domain of variable hydrophobicity. 3. We demonstrate, using a mouse melanoma model, that Tris-lipidated conjugates of the widely used cytotoxic and anti-inflammatory drug methotrexate (MTX) display enhanced potency in the local treatment of tumours and reduced systemic toxicity when compared with the unconjugated drug. 4. With genes now being predicted to be the pharmaceuticals of the future, we show that Tris-lipidated cationic peptides can efficiently deliver DNA into (transfect) cells in culture. Furthermore, by comparing the abilities of variants of these Tris-based cationic lipids to transfect cultured cells, we demonstrate that modifications made to variable regions of Tris-lipidated compounds can dramatically alter their delivery profiles.

Animals↗
PubMed2000

Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group.

BACKGROUND & AIMS: Appropriate management of primary gastric lymphoma is controversial. This prospective, multicenter study aimed to evaluate the accuracy of endoscopic biopsy diagnosis and clinical staging procedures and assess a treatment strategy based on Helicobacter pylori status and tumor stage and grade. METHODS: Of 266 patients with primary gastric B-cell lymphoma, 236 with stages EI (n = 151) or EII (n = 85) were included in an intention-to-treat analysis. Patients with H. pylori-positive stage EI low-grade lymphoma underwent eradication therapy. Nonresponders and patients with stage EII low-grade lymphoma underwent gastric surgery. Depending on the residual tumor status and predefined risk factors, patients received either radiotherapy or no further treatment. Patients with high-grade lymphoma underwent surgery and chemotherapy at stages EI/EII, complemented by radiation in case of incomplete resection. RESULTS: Endoscopic-bioptic typing and grading and clinical staging were accurate to 73% and 70%, respectively, based on the histopathology of resected specimens. The overall 2-year survival rates for low-grade lymphoma did not differ in the risk-adjusted treatment groups, ranging from 89% to 96%. In high-grade lymphoma, patients with complete resection or microscopic tumor residuals had significantly better survival rates (88% for EI and 83% for EII) than those with macroscopic tumor residues (53%; P < 0.001). CONCLUSIONS: There is a considerable need for improvement in clinical diagnostic and staging procedures, especially with a view toward nonsurgical treatment. With the exception of eradication therapy in H. pylori-positive low-grade lymphoma of stage EI and the subgroup of locally advanced high-grade lymphoma, resection remains the treatment of choice. However, because there is an increasing trend toward stomach-conserving therapy, a randomized trial comparing cure of disease and quality of life with surgical and conservative treatment is needed.

Adult↗
PubMed2000

Analysis of radon-associated squamous cell carcinomas of the lung for a p53 gene hotspot mutation.

Squamous cell lung carcinomas (SCC) from former employees of the Wismut uranium mining company (Saxony, Germany) were obtained from the Stollberg Archive in order to screen for p53 tumour suppressor gene codon 249 arg-->met hotspot mutations, a putative molecular bio-dosimeter of alpha-particle (radon) exposure (Taylor et al (1994) Lancet 343: 86-87; McDonald et al (1995) Cancer Epidemiol Biomarkers Prevent 4: 791-793). Of the 29 archived samples of SCC meeting quality criteria for DNA analysis by polymerase chain reaction (PCR) and Haelll restriction enzyme digestion, two tumours were found that harboured this mutation. DNA sequencing confirmed the presence of a G to T base substitution within the Haelll site spanning codons 249 and 250 of the p53 gene that results in replacement of arginine (wild-type) by methionine at residue 249. When these data are combined with those from our previous study of tumours from the Stollberg Archive in which 50 lung tumours were examined, (including nine SCCs), we conclude that the G-->T (arg-->met) codon 249 mutation prevalence in the Wismut miner cohort is not sharply elevated in lung cancers in general (two mutations/79 tumours), or specifically in SCCs of the lung (two mutations/38 SCC) when compared to data from lung cancer patients with no reported occupational exposure to radon gas.

Carcinoma, Squamous Cell↗
PubMed2000

Echoplanar magnetic resonance imaging in acute stroke.

Echoplanar magnetic resonance imaging (EPI) enables rapid, non-invasive imaging and analysis of cerebral pathophysiology in acute stroke. It represents an important clinical advance over computed tomography (CT) and conventional magnetic resonance (MR) scanning. It can rapidly delineate infarcted cerebral tissue and distinguish acute from chronic stroke. In addition, EPI has the potential to quickly determine the presence and degree of potentially viable brain tissue in the ischaemic penumbra. Thrombolysis is thought to reperfuse the penumbra and hence reduce infarct size. The thrombolytic agent tissue plasminogen activator (t-PA) improves outcome in ischaemic stroke when administered within the first 3 hours of onset. However, there is a significant risk of haemorrhage, and the time window for benefit may well exceed 3 hours in some patients. Hence, by facilitating diagnosis of 'at-risk' tissue in the ischaemic penumbra, a major clinical role of EPI may well become the rational selection of patients for acute interventional stroke therapy.

Brain↗
PubMed2000

Biodegradable progesterone microsphere delivery system for osteoporosis therapy.

The purpose of this study was to formulate and characterize a controlled-release biodegradable delivery system of progesterone for the treatment or prevention of osteoporosis. Microspheres of progesterone were formulated using copolymers of poly(glycolic acid-co-dl-lactic acid) (PGLA 50/50 and PGLA 15/85) and poly(L-lactic acid) (L-PLA) of similar molecular weight by the emulsion solvent evaporation technique. The effects of process variables, such as volume fraction, polyvinyl alcohol (PVA) concentration, polymer composition, and stir speed during preparation, on the yield, encapsulation efficiency (EEF), particle size distribution, in vitro release profiles of progesterone, and surface morphology of progesterone microspheres were investigated. Increasing the volume fraction from 9% to 22% increased the EEF without significantly increasing the yield; however, the rate of progesterone release from the microspheres decreased. Increasing the PVA concentration from 1% to 5% had no significant influence on the EEF, but the rate of progesterone release from microspheres increased. Polymer composition had no significant effect on the EEF, but had a significant effect on the particle size distribution, surface morphology, and release rate of progesterone from the microspheres. Stir speed did not have a significant influence on the EEF; however, stir speed influenced particle size distribution and the rate of progesterone release from microspheres of the same sieve-size range. The results suggest that controlled release of progesterone is possible by varying the different process variables, and that PGLA 50/50 provided the slowest release of progesterone. This should provide a means of delivering progesterone for months for the treatment or prevention of osteoporosis in postmenopausal women.

Antimicrobial Cationic Peptides↗
PubMed2000

Coreceptor-dependent inhibition of the cell fusion activity of simian immunodeficiency virus Env proteins.

The cytoplasmic tail (R peptide) sequence is able to regulate the fusion activity of the murine leukemia virus (MuLV) envelope (Env) protein. We have previously shown that this sequence exerts a profound inhibitory effect on the fusion activity of simian immunodeficiency virus (SIV)-MuLV chimeric Env proteins which contain the extracellular and transmembrane domains of the SIV Env protein. Recent studies have shown that SIV can utilize several alternative cellular coreceptors for its fusion and entry into the cell. We have investigated the fusion activity of SIV and SIV-MuLV chimeric Env proteins using cells that express different coreceptors. HeLa cells were transfected with plasmid constructs that carry the SIV or SIV-MuLV chimeric Env protein genes and were overlaid with either CEMx174 cells or Ghost Gpr15 cells, which express the Gpr15 coreceptor for SIV, or Ghost CCR5 cells, which express CCR5, an alternate coreceptor for SIV. The R-peptide sequence in the SIV-MuLV chimeric proteins was found to inhibit the fusion with CEMx174 cells or Ghost Gpr15 cells. However, a significant level of fusion was still observed when HeLa cells expressing the chimeric Env proteins were cocultivated with Ghost CCR5 cells. These results show that the R-peptide sequence exerts differential effects on the fusion activity of SIV Env proteins using target cells that express alternative coreceptors.

Animals↗
PubMed2000

Human monoclonal antibodies that inhibit binding of hepatitis C virus E2 protein to CD81 and recognize conserved conformational epitopes.

The intrinsic variability of hepatitis C virus (HCV) envelope proteins E1 and E2 complicates the identification of protective antibodies. In an attempt to identify antibodies to E2 proteins from divergent HCV isolates, we produced HCV E2 recombinant proteins from individuals infected with HCV genotypes 1a, 1b, 2a, and 2b. These proteins were then used to characterize 10 human monoclonal antibodies (HMAbs) produced from peripheral B cells isolated from an individual infected with HCV genotype 1b. Nine of the antibodies recognize conformational epitopes within HCV E2. Six HMAbs identify epitopes shared among HCV genotypes 1a, 1b, 2a, and 2b. Six, including five broadly reactive HMAbs, could inhibit binding of HCV E2 of genotypes 1a, 1b, 2a, and 2b to human CD81 when E2 and the antibody were simultaneously exposed to CD81. Surprisingly, all of the antibodies that inhibited the binding of E2 to CD81 retained the ability to recognize preformed CD81-E2 complexes generated with some of the same recombinant E2 proteins. Two antibodies that did not recognize preformed complexes of HCV 1a E2 and CD81 also inhibited binding of HCV 1a virions to CD81. Thus, HCV-infected individuals can produce antibodies that recognize conserved conformational epitopes and inhibit the binding of HCV to CD81. The inhibition is mediated via antibody binding to epitopes outside of the CD81 binding site in E2, possibly by preventing conformational changes in E2 that are required for CD81 binding.

Amino Acid Sequence↗
PubMed2000

Expression characteristics and relevance of sodium glucose cotransporter-1 in mammalian renal tubulogenesis.

Expression and role of sodium glucose cotransporter (SGLT-1) in tubulogenesis were investigated during renal development. A mouse SGLT-1 cDNA was cloned, and it had substantial homology with human and rat forms. Four mRNA transcripts were detected, which differed in size from other species. SGLT-1 transcripts were detected at day 13 of gestation, and their expression increased during later stages extending into the postnatal period. A high mRNA and protein expression of SGLT-1 was seen in tubular segments of the inner cortex and outer medulla at day 16, and it was developmentally regulated. Treatment with SGLT-1 antisense selectively decreased the population of tubules in the metanephric explants. Expression of glomerular mRNA and WGA binding were unchanged. SGLT-1 activity, as measured by [(14)C]methyl-alpha-D-glucopyranoside uptake, increased during gestation in the tubular segments where it is expressed. Glucose uptake was inhibited by the treatment with SGLT-1 antisense and D-galactose. The data suggest that SGLT-1 exhibits a restricted spatiotemporal expression with functional activity confined to the corresponding tubular segments, and it selectively maintains renal tubulogenesis during development.

Amino Acid Sequence↗
PubMed2000

Temporal arteritis and fever: report of a case and a clinical reanalysis of 360 cases.

The purposes of this article are to report a case with temporal arteritis (TA) and to summarize and reanalyze the cases of temporal arteritis associated with fever in published articles for understanding better the clinical features of TA. A case with biopsy-proven TA is reported. The publications with TA and fever were searched by using MEDLINE in English from 1966 to 1999. Three hundred sixty cases of temporal arteritis associated with fever were reanalyzed. The results showed that a case of biopsy-proven TA with typically clinical manifestation was initially misdiagnosed and that the reanalysis of 360 cases revealed that the common clinical findings at presentation were abnormal temporal arteries, headache, low fever, loss of weight, polymyalgia rheumatica, jaw claudication, vision disorder, arthralgis or myalyias, and ear pain and that the uncommon clinical findings at presentation were high fever, malaise, anorexia, breast pain, transient ischemic attack/stroke, cough, mental disorder, diarrhea, and uterine prolapse, etc. Laboratory findings were the range of erythrocyte sedimentation rate (ESR) 14 to 149 with a mean of 97.0 mm/hr, white blood cells being normal or increased in the range of 10.9 to 22.9 x 10(9)/L, hemoglobin level 7 to 16 g/dL, the platelets count increased to 785 x 10(9)/L, and microscopic hematuria. The diagnosis was made by a combination of clinical features, an increased ESR, a response to steroids, and, most specifically, temporal artery biopsy. The initial diagnosis was misdiagnosed in 38.2% of patients. In conclusion, the features of TA associated with fever have not been widely appreciated yet. TA is a common cause of fever of unknown origin (FUO) in the elderly. TA should be considered when patients complain of common and uncommon manifestations. An elevated ESR will aid in the diagnosis of TA, and temporal artery biopsy will provide certainty.

Adult↗
PubMed2000

Linkage of the genes controlling natural killer cell activity to HLA-B.

OBJECTIVE: To study whether there is a relationship between HLA-B alleles and low natural killer(NK) cell activity in Chinese. METHODS: The subjects were 34 unrelated healthy individuals (10 males and 24 females), aged 25-60 years, and 31 individuals (17 males and 14 females) from 11 families, aged 22-70 years, previously genotyped for HLA class I, II, complotypes and haplotypes that were assigned based on family studies. The unrelated individuals were typed for HLA-A, -B antigen by a microcytotoxicity assay and all the subjects were tested for NK cell activity by lactate dehydrogenase (LDH) enzyme-release assay. RESULTS: Statistical analysis showed that 30 lysis unit(LU) was the cutoff value of low and high NK reactors. The frequency of low reactor individuals homozygous for HLA-B was significantly higher than that for those for HLA-DR(P< 0. 05). The associated genes included HLA-B13, B40, B46, B7, B57, defined as NKB1 genes, and HLA-B44 as NKB2 gene. Family studies provide further evidence that the genes controlling low NK cell activity were located in the MHC region and it was a recessive trait. CONCLUSION: There were recessive genes associated with HLA-B controlling low NK cell activity in Chinese. The NKB alleles were partly different from those found in Caucasian.

Adult↗
PubMed2000

[The in vivo degradation, adsorption and excretion of poly(epsilon-caprolactone)].

The in vivo degradation of poly(epsilon-caprolactone(PCL) was studied in rats. The results showed that the PCL capsules with an initial molecualr weight of 66,000 stayed intact in vivo for 2 years, although the molecular weight of the capsules gradually declined during the two-year implantation. It then degraded into low molecular wight pieces with the extension of the implantation. Tritium-labeled low molecular weight PCL was subcutaneously implanted in rats to further investigate the absorption and excretion of the material. The radioactivity was first detected in blood 15 days post the implantation. At the same time radioactive excreta were recovered from feces and urine. An accumulative 92% of the implanted radioactive dosage was excreted from feces and urine 135 days post the implantation. In the meanwhile, the blood radioactivity dropped to the background level. Radioactivity in the organs was all close to the background level indicating that the material did not cumulate in body tissue and could be completely excreted.

Absorption↗
PubMed2000

Parental smoking and alcohol consumption and risk of neuroblastoma.

Previous studies and animal evidence have suggested a relationship between parental tobacco or alcohol use and the risk of some childhood cancers, including neuroblastoma. A case-control study was conducted to investigate the relationship between parental tobacco smoking, alcohol consumption, and risk of neuroblastoma. Cases were children diagnosed with neuroblastoma over the period 1992-1994 at Children's Cancer Group and Pediatric Oncology Group institutions throughout the United States and Canada. One matched control was selected using random-digit dialing. Information on parental smoking and drinking history was obtained from 504 case and 504 control parents by telephone interview. Overall, there was no consistent pattern of association with parental smoking and alcohol consumption. For example, both maternal smoking and drinking during the period from 1 month before pregnancy through breastfeeding had adjusted odds ratios (ORs) of 1.1 [95% confidence interval (CI), 0.8-1.4]. There was no association with paternal smoking (OR, 1.2; 95% CI, 0.8-1.6) or paternal drinking 1 month before conception (OR, 1.0; 95% CI, 0.7-1.4). There was no consistent increase in risk by the amount of smoking or drinking during any time period relative to pregnancy. There was no suggestion of an increased risk when only one parent smoked. Smoking or drinking among both parents did not jointly increase the risk of neuroblastoma in their offspring. The child's age at diagnosis, stage, or MYCN oncogene amplification status did not materially alter the OR estimates. It is concluded that the results from this study do not indicate any evidence for a relationship between neuroblastoma and parental tobacco or alcohol use.

Adolescent↗
PubMed2000

Antisense inhibition of hMLH1 is not sufficient for loss of DNA mismatch repair function in the HCT116+chromosome 3 cell line.

We have reported that transfer of chromosome 3 (Chr3) containing a single wild-type copy of the hMLH1 gene into HCT116 colon cancer cells, a cell line deficient in DNA mismatch repair (MMR) activity attributable to inactivating hMLH1 mutations, corrects all of the aspects of the MMR repair-deficient phenotype. We inhibited the expression of the wild-type hMLH1 gene using antisense RNA in HCT116+Chr3 cells to determine if this would result in reversion to the MMR-deficient phenotype. Despite profound inhibition of hMLH1 expression, DNA MMR activity and alkylation sensitivity were not impaired in the antisense-transfected HCT116+Chr3 cells. Additionally, arrest of the cell cycle at the G2 phase with alkylation damage occurs in these cells, a phenotype associated with MMR proficiency. These results indicate that even with a reduction in the expression of hMLH1 protein below the limits of detection by Western blotting, DNA MMR activity remained fully functional (by direct DNA MMR activity assay). We would speculate that hMLH1 is expressed in substantially greater abundance than would be minimally necessary for DNA MMR and that minor reductions in the expression of this protein would not be sufficient to permit DNA MMR dysfunction. Alternatively, Chr3 may contain a second hMLH1 homologue that might overlap with the function of hMLH1.

Adaptor Proteins, Signal Transducing↗
PubMed2000

[Some geographical features of the location and gene mutation of cancers occurring in Nantong City, China].

OBJECTIVE: To detect the location and geographical features of gene mutation of the cancer based on 30,709 clinical tumor biopsies. METHODS: Thirty thousand seven hundred and nine cases of tumor biopsy materials were collected from the Department of Pathology of Nantong Cancer Hospital between June 1974 and December 1987. The address of the village and county of patients was collected and statistical analysis was performed on data from lab examination. DNA sequencing of 31 cases of hepatocellular carcinoma (HCC) was performed at the Department of Pathology of the Medical College of Tokyo University, Japan. RESULTS: The data suggested that different carcinomas occurred predominantly in some districts and the frequency and type of mutation of the P53 gene in the HCC were different in different districts. CONCLUSION: It seems that based on the clinical biopsy materials, carcinomas of the uterus cervix (CC) and nasopharynx tend to occur in some districts of Nantong City and the frequency and type of mutation of the gene P53 of the HCC were different in different districts. The reason for this is not understood and further study will be done.

China↗
PubMed2000

The effect of transient balloon occlusion of the mitral valve on left atrial appendage blood flow velocity and spontaneous echo contrast: a comparison in sinus rhythm and atrial fibrillation patients.

OBJECTIVE: To investigate the relationship between spontaneous echo contrast (SEC) and left atrial appendage (LAA) blood flow velocity using transesophageal echocardiography (TEE) during percutaneous balloon mitral valvotomy (PBMV) in patients with atrial fibrillation and sinus rhythm. METHODS: Thirty-five patients (21 in sinus rhythm and 14 in atrial fibrillation) with rheumatic mitral stenosis underwent PBMV with intraoperative transesophageal echocardiography monitoring. We measured LAA blood flow velocities and observed the left atrium for various grades of SEC (from 0 = none to 4 = severe), before and after each balloon inflation. RESULTS: Left atrial appendage maximal emptying velocity (LAA MEV) was reduced from 35 +/- 14 cm/s to 6 +/- 2 cm/s at peak balloon inflation and increased to 40 +/- 16 cm/s after balloon deflation. Comparison of the values before balloon inflation and after balloon deflation showed that LAA velocities were significantly lower (P < 0.001). During balloon inflation, both maximal emptying velocity (MEV) and maximal filling velocity (MFV) were significantly decreased, compared to those before inflation and after balloon deflation (P < 0.01). And both MEV and MFV were significantly higher after balloon deflation relative to those before balloon inflation. Patients with atrial fibrillation had significantly lower MEV and MFV before and during balloon inflation and after balloon deflation than patients with sinus rhythm. At peak balloon inflation, new or increased SEC grades were observed during 54 of 61 (88%) inflations and unchanged during 7 (12%) inflations. SEC grades were reduced after 55 balloon deflations (90%), completely disappeared after 18 deflations (30%) and remained unchanged after 6 deflations (10%). At peak balloon inflation, left atrium spontaneous echo contrast (LASEC) grade 4 was observed during 14 of 27 (93%) inflations in the atrial fibrillation patients, significantly higher than in patients with sinus rhythm (8 of 34, 24%; P < 0.05). LASEC completely disappeared after 16 of 34 deflations (47%) in the patients with sinus rhythm, significantly higher than in the atrial fibrillation patients (2 of 27 deflations; P < 0.01). The mean time to achieve maximal SEC grade (2.5 +/- 1.2 s) correlated with the mean time to trough LAA velocities (2.3 +/- 1.1 s) after balloon inflation. Both the time to lowest LAA velocity and the time to highest LASEC were significantly longer in the patients with sinus rhythm than in the atrial fibrillation patients (2.6 +/- 1.1 s vs 1.7 +/- 1.0 s, P < 0.05 and 2.8 +/- 1.4 s vs 1.9 +/- 1.3 s, P < 0.05, respectively). Upon deflation, the mean time to lowest SEC grade (2.9 +/- 1.8 s) correlated with the mean time to achieve maximal LAA velocities (2.7 +/- 1.6 s). Both intervals are significantly shorter in the patients with sinus rhythm than in the atrial fibrillation patients (2.0 +/- 1.6 s vs 3.5 +/- 1.5 s, P < 0.01 and 2.2 +/- 1.7 s vs 3.6 +/- 1.6 s, P < 0.05). CONCLUSION: Reducing the blood flow velocity in the human left atrium by balloon occlusion of the mitral valve may enhance SEC, whereas restoring blood flow after balloon deflation would cause enhanced echogenic blood to disappear or decrease in both groups of patients. Patients with atrial fibrillation demonstrate more severe blood stagnation of the left atrial body and appendage during transient balloon inflation at mitral valve orifice and slower recovery from the stagnation, decreasing to a lesser extent after balloon deflation, when compared to patients with sinus rhythm.

Adolescent↗