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Biomedical subjects

T Liu

Publications and source records attributed to T Liu.

At least 19 recordsLinked to original sources
PubMed1999

Macrophage control of herpes simplex virus type 1 replication in the peripheral nervous system.

After corneal infection, herpes simplex virus type 1 (HSV-1) invades sensory neurons with cell bodies in the trigeminal ganglion (TG), replicates briefly, and then establishes a latent infection in these neurons. HSV-1 replication in the TG can be detected as early as 2 days after corneal infection, reaches peak titers by 3-5 days after infection, and is undetectable by 7-10 days. During the period of HSV-1 replication, macrophages and gammadelta TCR+ T lymphocytes infiltrate the TG, and TNF-alpha, IFN-gamma, the inducible nitric oxide synthase (iNOS) enzyme, and IL-12 are expressed. TNF-alpha, IFN-gamma, and the iNOS product nitric oxide (NO) all inhibit HSV-1 replication in vitro. Macrophage and gammadelta TCR+ T cell depletion studies demonstrated that macrophages are the main source of TNF-alpha and iNOS, whereas gammadelta TCR+ T cells produce IFN-gamma. Macrophage depletion, aminoguanidine inhibition of iNOS, and neutralization of TNF-alpha or IFN-gamma all individually and synergistically increased HSV-1 titers in the TG after HSV-1 corneal infection. Moreover, individually depleting macrophages or neutralizing TNF-alpha or IFN-gamma markedly reduced the accumulation of both macrophages and gammadelta TCR+ T cells in the TG. Our findings establish that after primary HSV-1 infection, the bulk of virus replication in the sensory ganglia is controlled by macrophages and gammadelta TCR+ T lymphocytes through their production of antiviral molecules TNF-alpha, NO, and IFN-gamma. Our findings also strongly suggest that cross-regulation between these two cell types is necessary for their accumulation and function in the infected TG.

Animals↗
PubMed1999

Effect of systemic cyclosporine on tumor recurrence after liver transplantation in a model of hepatocellular carcinoma.

BACKGROUND: Long-term results after liver transplantation for hepatocellular carcinoma have been disappointing, largely because of the high recurrence rate. It is controversial whether the immunosuppressed state of the recipient contributes to this recurrence rate. We have developed a model in the rat system to examine the effect of immunosuppression on tumor recurrence after transplantation, as well as to evaluate other treatment strategies to decrease the recurrence rate. METHODS: A 2-mm3 nodule of Morris hepatoma 3924a was implanted intrahepatically at day 0. At postimplant day 16, the animals underwent syngeneic orthotopic liver transplantation. Two treatment groups were established. Group I received saline injections subcutaneously for 2 weeks, while group II received subcutaneous cyclosporine injections at 3 mg/kg/day for 14 days. Animal survival, tumor recurrence rate, and sites of recurrence and number of pulmonary nodules were recorded. RESULTS: Overall survival rate was reduced in animals receiving cyclosporine. The mean survival time was 74.4 days (SEM 6.39 days) in saline-treated animals and 50.4 days (SEM 7.63 days) in the cyclosporine-treated animals. The proportion surviving in group 1 was 47% and in group 2 was 18%. This difference in survival was statistically significant (P=0.025). The incidence of pulmonary nodules was increased in the cyclosporine-treated animals, and tumor recurrence in extrapulmonary sites was seen only in the cyclosporine-treated animals. CONCLUSION: Results from this study suggest that cyclosporine has an adverse effect on tumor recurrence after transplantation. This model will be useful to further examine treatment strategies to improve the outcome of transplantation for hepatocellular carcinoma.

Animals↗
PubMed1999

Zinc alleviates thermal hyperalgesia due to partial nerve injury.

Zinc has recently been shown to alleviate inflammatory hyperalgesia. In the present study, we showed that intrathecal, intraplantar or systemic injection of zinc chloride significantly relieved thermal hyperalgesia in rats with sciatic nerve injury. Alleviation of thermal hyperalgesia was dose dependent in each case, although higher doses were required for i.p. injections (ED50 = 13.6 nmol) than for intrathecal (ED50 = 0.05 nmol) or intraplantar injections (ED = 0.3 nmol). Neither intrathecal nor intraplantar zinc chloride influenced thermal nociception in normal rats without nerve injury. The results provide the first evidence that zinc alleviates neuropathic hyperalgesia.

Animals↗
PubMed1999

Nested case-control study of esophageal cancer in relation to occupational exposure to silica and other dusts.

BACKGROUND: Standardized proportionate mortality ratio (SPMR) was found to be 2.2 (95% CI = 1.3-3.5) for esophageal cancer (EC) among workers exposed to refractory brick dust in a large iron-steel complex in China. METHODS: A nested case-control design within a cohort of industrial workers. One hundred and twenty-five EC cases and 250 controls were identified from the death registry file. Interviews were conducted of the next of kin for past exposure information on job, domestic, and lifestyle factors. History of occupational exposure to various dusts was reconstructed from personnel files and by interviewing colleagues utilizing a job-exposure matrix. RESULTS: After adjusting for confounders, occupational exposure to silica dust was the most important risk factor among all variables investigated, with a 2.8-fold risk and a clear dose-response by length of exposure. Alcohol drinking (OR = 1.8) and coal cooking (OR = 2.0) were risk factors and high consumption of fruit diet (OR = 0.5) and meat diet (OR = 0.6) were protective factors. CONCLUSIONS: The relationship between occupational exposure to silica dust and the risk of EC found in an earlier SPMR study was confirmed. Ingestion of silica particles after lung clearance may increase the risk of EC among workers exposed to silica.

Aged↗
PubMed1999

Acetylcholine receptor alpha subunit mRNA expression in human thymus: augmented expression in myasthenia gravis and upregulation by interferon-gamma.

Previous studies by us and others have demonstrated the expression of acetylcholine receptors on epithelial cells in the thymus of myasthenia gravis (MG) and control subjects. In the present experiments, we used a reverse transcription-polymerase chain reaction (RT-PCR) to analyze the profile of the two major isoforms of the alpha chain of these receptors (AChRalpha), P3A- and P3A+, in thymus tissue obtained from MG and control subjects and a human thymic epithelial cell line (TEC9). In addition, using a semiquantitative RT-PCR, we compared the amounts of P3A- and P3A+ mRNA expressed in thymic tissue obtained from these two sources and determined if their expression in TEC9 is modulated by cytokines. We found that mRNAs encoding P3A- and P3A+ are expressed at approximately a 5:1 ratio in both MG and control thymus tissue. This contrasts with skeletal muscle where mRNAs encoding these isoforms are expressed equally. A pattern of preferential P3A- vs P3A+ mRNA expression was also observed in TEC9. We observed 2.8-fold greater expression of both isoforms in MG than in control thymus. Expression of both isoforms in TEC9 was enhanced significantly by treatment with interferon-gamma whereas IL-1alpha, IL-4, and IL-6 had no effect. Thus, there is differential regulation of AChRalpha variants in thymus and TEC relative to muscle and interferon-gamma represents a novel regulator of AChRalpha mRNA expression. MG thymus is distinguished by increased expression of both isoforms of this autoantigen, a finding that may reflect enhancement of transcription by local microenvironmental factors.

Adolescent↗
PubMed1999

Cincinnati Prehospital Stroke Scale: reproducibility and validity.

STUDY OBJECTIVE: The Cincinnati Prehospital Stroke Scale (CPSS) is a 3-item scale based on a simplification of the National Institutes of Health (NIH) Stroke Scale. When performed by a physician, it has a high sensitivity and specificity in identifying patients with stroke who are candidates for thrombolysis. The objective of this study was to validate and verify the reproducibility of the CPSS when used by prehospital providers. METHODS: The CPSS was performed and scored by a physician certified in the use of the NIH Stroke Scale (gold standard). Simultaneously, a group of 4 paramedics and EMTs scored the same patient. RESULTS: A total of 860 scales were completed on a convenience sample of 171 patients from the emergency department and neurology inpatient service. Of these patients, 49 had a diagnosis of stroke or transient ischemic attack. High reproducibility was observed among prehospital providers for total score (intraclass correlation coefficient [rI],.89; 95% confidence interval [CI],.87 to.92) and for each scale item: arm weakness, speech, and facial droop (.91,.84, and.75, respectively). There was excellent intraclass correlation between the physician and the prehospital providers for total score (rI,.92; 95% CI,.89 to.93) and for the specific items of the scale (.91,.87, and.78, respectively). Observation by the physician of an abnormality in any 1 of the 3 stroke scale items had a sensitivity of 66% and specificity of 87% in identifying a stroke patient. The sensitivity was 88% for identification of patients with anterior circulation strokes. CONCLUSION: The CPSS has excellent reproducibility among prehospital personnel and physicians. It has good validity in identifying patients with stroke who are candidates for thrombolytic therapy, especially those with anterior circulation stroke.

Aged↗
PubMed1999

Acute stroke: delays to presentation and emergency department evaluation.

STUDY OBJECTIVE: To document prehospital and inhospital time intervals from stroke onset to emergency department evaluation and to identify factors associated with presentation to the ED within 3 hours of symptom onset, the current time window for thrombolytic therapy. METHODS: Patients admitted through the ED with a diagnosis of stroke were identified through admitting logs. Time intervals were obtained from EMS runsheets and ED records. Information regarding first medical contact, education, and income was obtained by patient interview. Baseline variables were analyzed to assess association with ED arrival within 3 hours of symptom onset; variables significant on univariate analysis were placed in a multivariable model. RESULTS: There were 151 stroke patients (59% white and 41% black). Time of stroke onset and time to ED arrival were documented for 119 patients (79%). The median time from stroke onset to ED arrival was 5.7 hours; 46 patients (30%) presenting within 3 hours. Of those with times recorded, the median time from stroke onset to EMS arrival was 1.7 hours. Multivariable logistic regression identified use of EMS (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.3 to 12.1) and white race (OR, 3.5; 95% CI, 1.3 to 10) as being independently associated with ED arrival within 3 hours of symptom onset. Median time from ED arrival to physician evaluation was 20 minutes. Median time from ED arrival to computed tomographic evaluation was 72 minutes. When patients were asked the main reason they sought medical attention, 40% (60/141) of those able to be interviewed said that they themselves did not decide to seek medical attention, but rather a friend or family member told them they should go to the hospital. CONCLUSION: The median time from stroke onset to ED evaluation was 5.7 hours, with almost a third of patients presenting within 3 hours. Use of EMS and white race were independently associated with arrival within 3 hours.

Acute Disease↗
PubMed1999

Major concerns and needs of breast cancer patients.

Between 1989 and 1991, 102 breast cancer patients completed a questionnaire survey on concerns and needs at their first visit to the University Clinic after they were diagnosed or treated for breast cancer at other clinics. Their major concerns and needs were health, family, finances, work, the future, self-esteem, counseling and support for themselves and their family. Married women and those younger than 50 years were more likely to have concerns about their family. Nonwhites had more concerns about finances and work than white women, with an odds ratio (OR) of 6.58. Older women and those married, however, had less concerns about finances and work than younger women and those not married, with ORs of 0.96 and 0.34, respectively. Fewer nonwhite than white patients expressed concerns about their future (OR = 0.31). Young women were more concerned about self-esteem than older women. More nonwhites than whites and more married than unmarried women expressed needs for family counseling and support (OR = 3.58 and 3.68, respectively). Help for interpreting information was required more frequently by nonwhites than whites (OR = 7.25, 95% confidence interval [CI] = 2.19-24.00). Nonwhite women also tended to require more referrals than whites. In summary, major concerns and needs varied among patients of different demographic characteristics, especially those of age, race, and marital status.

Adaptation, Psychological↗
PubMed1999

Immunopotentiating activity of nigerooligosaccharides for the T helper 1-like immune response in mice.

The immunopotentiating activity of nigerooligosaccharides (NOS), a mixture of nigerose, nigerosyl glucose and nigerosyl maltose, was studied in vitro and in vivo in mice. Mitogen-induced proliferation of splenocytes from normal mice was augmented in a dose-dependent manner by nigerose of NOS. NOS enhanced interleukin 12 (IL-12) and interferon-gamma (IFN-gamma) production by normal splenocytes in the presence of the potent IL-12 inducer, heat-killed Lactobacillus plantarum L-137, in vitro. Consistent with the in vitro finding, L. plantarum L-137-induced IL-12 production and IL-2-induced IFN-gamma production were augmented in mice fed with a 14.6% NOS diet for 2 weeks compared with mice fed with a control diet. Notably, mice fed with the NOS diet showed significantly longer survival time than the control mice after the induction of an endogenous infection by administering 5-fluorouracil in a lethal dose. Taken together, these results suggest that NOS may exert immunopotentiating activity through the activation of an IL-12-dependent T helper 1-like immune response.

Animals↗
PubMed1998

Identification of two regions in the cytoplasmic domain of CD44 through which PMA, calcium, and foskolin differentially regulate the binding of CD44 to hyaluronic acid.

CD44 contains two clustered basic residues of three arginines and three lysines in the membrane-proximal region of its cytoplasmic domain. These two clusters are conserved among different species and different splicing forms. The function of these two motifs is not known. We substituted either the three-arginine or the three-lysine motif with alanine (CD44.3R3A and CD44.3K3A) and established stable CD44 transfectants. The effects of these mutations on the binding of CD44 to one of its ligands, hyaluronic acid (HA), were studied. When stimulated with PMA, transfectants bearing CD44.3K3A and CD44.3R3A proteins have reduced HA-binding capacity. When stimulated with forskolin, an activator of cAMP-dependent PKC, CD44.3R3A transfectants were able to bind low but detectable level of fluorescent-conjugated HA (F-HA). In contrast, CD44.3K3A transfectants were unable to bind any F-HA. Elevation of intracellular calcium concentrations either by ionomycin or thapsigargin also induced binding of HA in CD44.3R3A but not in CD44. 3K3A transfectants. These results provide evidence that both the arginine and the lysine motifs are important in the binding of CD44 to high levels of HA when stimulated with PMA. In contrast, when transfectants were stimulated with either forskolin or a Ca2+ mobilizer to bind a low level of F-HA, the lysine cluster, but not the arginine cluster, is required. These two closely located basic clusters are, therefore, differentially involved in the binding of CD44 to HA, depending on the level of ligand binding and the nature of the stimulatory signals.

Arginine↗
PubMed1998

Mass spectrometric sequencing of site-specific carcinogen-modified oligodeoxyribonucleotides containing bulky benzo[a]pyrene diol epoxide-deoxyguanosyl adducts.

Site-specific carcinogen-modified oligonucleotides are often used in site-directed mutagenesis and other biological and biochemical studies of structure-function relationships. Postsynthetic analysis and confirmation of the sites of carcinogen binding in such oligonucleotides is an important step in the characterization of these site-specific carcinogen-DNA adducts. It is shown here that negative ion mode electrospray tandem mass spectrometry methods and collision-induced dissociation offer a rapid and convenient approach for the sequencing of products derived from the reaction of the carcinogenic and mutagenic metabolite of benzo[a]pyrene, the diol epoxide r7,t8-dihydroxy-t9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE), with the 11-mer oligonucleotide d(CATGCGGCCTAC). The site of reaction of anti-BPDE with either one of the three dG residues in this oligonucleotide can be accurately established by comparing the mass/charge ratios of the observed collision-induced dissociation fragments with calculated values.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1998

Mutagenic potential of stereoisomeric bay region (+)- and (-)-cis-anti-benzo[a]pyrene diol epoxide-N2-2'-deoxyguanosine adducts in Escherichia coli and simian kidney cells.

We have investigated the mutagenic potential of site-specifically positioned DNA adducts with (+)- and (-)-cis-anti stereochemistry derived from the binding of r7,t8-dihydroxy-t9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene (BPDE) to N2-2'-deoxyguanosine (G1 or G2) in the sequence context 5'TCCTCCTG1 G2CCTCTC. BPDE-modified oligodeoxynucleotides were ligated to a single-stranded DNA vector and replicated in Escherichia coli or simian kidney (COS7) cells. The presence of (+)- or (-)-cis adduct strongly reduced the yield of transformants in E. coli, and the yield was improved by the induction of SOS functions. Both adducts were mutagenic in E. coli and COS cells, generating primarily G --> T transversions. In E. coli, the (-)-cis adduct was more mutagenic than the (+)-cis adduct, while in COS cells, both adducts were equally mutagenic. These results were compared with those obtained with stereoisomeric (+)- and (-)-trans adducts [Moriya, M., et al. (1996) Biochemistry 35, 16646-16651). In E. coli, cis adducts, especially (-)-cis adducts, are consistently more mutagenic than the comparable trans adduct. In COS cells, trans adducts yield higher frequencies of mutations than the two cis adducts and, with the exception of the high-mutation frequency associated with the (+)-trans adduct at G2, relatively small differences in mutation frequencies are observed for the three other adducts. In E. coli, mutation frequency is a pronounced function of adduct stereochemistry and adduct position. These findings suggest that the fidelity of translesional synthesis across BPDE-dG adducts is strongly influenced by adduct stereochemistry, nucleotide sequence context, and the DNA replication complex.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1998

Mechanisms regulating the binding activity of CD44 to hyaluronic acid.

CD44 is a cell surface glycoprotein present on many cell types. Many CD44 isoforms have been identified. All CD44 isoforms utilize identical transmembrane and cytoplasmic domains. The hematopoietic form of CD44 (CD44H) is the major CD44 protein present on normal human lymphocytes and monocytes. One of the ligands for CD44 is hyaluronic acid (HA), a polymer consisting of repeat units of disaccharide; N-acetyl-D-glucosamine and N-acetyl-D-glucuronic acid. Since HA is present ubiquitously in extracellular matrix and in circulation, promiscuous binding of HA to CD44 may have undesirable affect. Similar to other adhesion molecules, binding of HA to cell surface CD44 requires regulation. In this review, we summarized our studies using a human lymphoma cell line, Jurkat. We found that binding of CD44+ Jurkat transfectants to HA requires cellular activation. Cellular activation induces the reorganization of the cytoskeleton proteins. Reorganization of cytoskeletal proteins results in clustering of CD44 on the cell surface. Clustering of CD44 on the cell surface is a prerequisite for the homodimerization of CD44. Our studies on Jurkat transfectants and results from other investigators suggest that interactions between CD44 and HA is a dynamic process and requires the participation of different cellular components; depending of the nature of the cell type and/or the nature of the activation signals.

Amino Acid Sequence↗
PubMed1998

[Detection of SMN gene deletions in spinal muscular atrophy].

OBJECTIVE: Survival motor neuron gene(SMN) and neuronal apoptosis inhibitory protein gene (NAIP) have been identified as the candidates of progressive spinal muscular atrophy (SMA)-determining genes. The aims of this study were to investigate the absence of SMN gene exon 7 in Chinese SMA patients, to confirm the relationship between the deletion of the SMN and SMA further, and to establish methods for gene diagnosis and prenatal diagnosis of SMA. METHODS: PCR-SSCP with silver staining method was used to detect the genomic DNA of 37 SMA patients and 30 normal individuals for deletions of SMN exon 7. RESULTS: Homozygous deletion of the SMN exon 7 was identified in 86.7%(13/15) of type I SMA patients and 86.4%(19/22) of type II patients. In the 88 controls (including parents of patients and normal individuals), homozygous absence of SMA exon 7 was only found in a mother of a patient. CONCLUSION: The data support that homozygous absence of SMN exon 7 is strongly associated with SMA. The percentage of homozygous deletions in this study is almost as high as that reported by other researchers. This method is useful, reliable and effective for gene diagnosis and prenatal diagnosis of SMA.

Cyclic AMP Response Element-Binding Protein↗
PubMed1998

Viscosity-adjustable block copolymer for DNA separation by capillary electrophoresis.

The viscosity-adjustable property of F127 block copolymer PEO99PPO69PEO99, PEO and PPO being poly(ethylene oxide) and poly(propylene oxide), respectively, was found to be useful for the development of automated capillary electrophoresis (CE). The polymer solution can form a gel-like structure with sieving ability and can also serve as a dynamic coating material, thereby effectively suppressing the electroosmotic flow induced by the ionization of the silanol group on the quartz capillary inner wall. When applied to CE as a separation medium, F127 block copolymer can provide the advantages of high separation resolution, easy injection and replacement of the triblock copolymer solution and convenient capillary column treatment. High reproducibility of DNA electrophoretic migration time in CE by replenishing F127 solution in acid-washed capillary tubings can be achieved. The relative standard deviation of the DNA migration time is less than 2%. In the investigation of F127 concentration and temperature effects on the performance of DNA separation in CE, we have found that the DNA electrophoretic migration behavior in the F127 gel-like solution cannot be described by any one of the existing models.

DNA↗
PubMed1998

Application of free-flow electrophoresis to the purification of trichosanthin from a crude product of acetone fractional precipitation.

The application of free-flow electrophoresis (FFE) to the purification of trichosanthin (TCS) from a crude product of acetone fractional precipitation was investigated. An electrophoresis technique, combining field step electrophoresis (FSE) and zone electrophoresis (ZE) to a one-step procedure, was optimized until a satisfactory purification factor (1.35), high resolution, and purity (>99%) were achieved. Testing several separation buffer systems revealed that a throughput of 14.2 mg/h can be obtained when the very basic TCS (pI 10.1) was dissolved and electrophoresed in a phosphate buffer system of pH 4. The purity of electrophoresed trichosanthin was proved by a variety of analytical methods, such as sodium dodecyl sulfate (SDS)-gel electrophoresis, capillary isoelectric focusing (CIEF), and sequencing of N- and C-termini. The high purity and large throughput achieved at low cost by using FFE indicates that this method can be employed for TCS purification.

Acetone↗
PubMed1998

Differential effects of bone mineral content and bone area on vertebral strength in a swine model.

Since the biomechanical competence of a vertebral body may be closely related to the content and distribution of the bone mineral, we have evaluated the effects of projected vertebral bone area (BA) and bone mineral parameters [bone mineral content (BMC) or bone mineral density (BMD)] on their biomechanical competence. We used dual-energy X-ray absorptiometry (DXA) to assess the bone mineral parameters of 36 swine thoracic vertebrae (T1-T12) and 15 lumbar vertebrae (L1-L5) after removal of the posterior elements. The failure load, compressive stress, and the stored strain energy of these vertebral bodies were assessed by a uniaxial compressive test using an MTS 810 testing system. Multiple regression analysis showed a significantly negative effect of BA and significantly positive effect of BMC on the biomechanical competence (compressive stress, r2 = 0.67, P < 0.0001; failure load, r2 = 0.75, P < 0.0001). However, the stored strain energy was only related to the BMC (r2 = 0.35, P < 0.0001). The contributory effects of BMC and BA on the biomechanical competence were not equal. The effects of BMC was larger than BA in determining the failure load and stored strain energy, whereas the reverse was found for the compressive stress. Using the log-transformed parameters as the regressors resulted in similar results. These results suggested the differential effects of BA and BMC in determining the biomechanical competence of vertebral bodies. We recommend the use of both parameters instead of BMD alone for evaluation of the vertebral biomechanical competence.

Absorptiometry, Photon↗