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Biomedical subjects

L Su

Publications and source records attributed to L Su.

At least 37 records · Page 2Linked to original sources
PubMed2001

Human immunodeficiency virus type 1 IIIB selected for replication in vivo exhibits increased envelope glycoproteins in virions without alteration in coreceptor usage: separation of in vivo replication from macrophage tropism.

Analysis of viral replication and pathogenicity after in vivo selection of human immunodeficiency virus type 1 (HIV-1) attenuated in vitro will help to define the functions involved in replication and pathogenesis in vivo. Using the SCID-hu Thy/Liv mouse and human fetal thymus organ culture as in vivo models, we previously defined HIV-1 env determinants (HXB2/LW) which were reverted for replication in vivo (L. Su et al., Virology 227:46-52, 1997). In this study, we examined the replication of four highly related HIV-1 clones directly derived from Lai/IIIB or after selection in vivo to investigate the envelope gp120 determinants associated with replication in macrophages and in the thymus models in vivo. The LW/C clone derived from the IIIB-infected laboratory worker and HXB2/LW both efficiently infected monocyte-derived macrophages (MDM) and the human thymus. Although the laboratory worker (LW) isolates showed altered tropism from IIIB, they still predominantly used CXCR4 as coreceptors for infecting peripheral blood mononuclear cells, macrophages, and the thymus. Interestingly, a single amino acid mutation in the V3 loop associated with resistance to neutralizing antibodies was also essential for the replication activity of the LW virus in the thymus models but not for its activity in infecting MDM. The LW virions were equally sensitive to a CXCR4 antagonist. We further demonstrated that the LW HIV-1 isolate selected in vivo produced more infectious viral particles that contained higher levels of the Env protein gp120. Thus, selection of the laboratory-attenuated Lai/IIIB isolate in vivo leads to altered tropism but not coreceptor usage of the virus. The acquired replication activity in vivo is correlated with an early A-to-T mutation in the V3 loop and increased virion association of HIV-1 Env gp120, but it is genetically separable from the acquired replication activity in macrophages.

Animals↗
PubMed2001

Separation of human immunodeficiency virus type 1 replication from nef-mediated pathogenesis in the human thymus.

Human immunodeficiency virus type 1 (HIV-1) is frequently attenuated after long-term culture in vitro. The attenuation process probably involves mutations of functions required for replication and pathogenicity in vivo. Analysis of attenuated HIV-1 for replication and pathogenicity in vivo will help to define these functions. In this study, we examined the pathogenicity of an attenuated HIV-1 isolate in a laboratory worker accidentally exposed to a laboratory-adapted HIV-1 isolate. Using heterochimeric SCID-hu Thy/Liv mice as an in vivo model, we previously defined HIV-1 env determinants (HXB/LW) that reverted to replicate in vivo (L. Su, H. Kaneshima, M. L. Bonyhadi, R. Lee, J. Auten, A. Wolf, B. Du, L. Rabin, B. H. Hahn, E. Terwilliger, and J. M. McCune, Virology 227:46-52, 1997). Here we further demonstrate that HIV-1 replication in vivo can be separated from its pathogenic activity, in that the HXB/LW virus replicated to high levels in SCID-hu Thy/Liv mice, with no significant thymocyte depletion. Restoration of the nef gene in the recombinant HXB/LW genome restored its pathogenic activity, with no significant effect on HIV-1 replication in the thymus. Our results suggest that in vitro-attenuated HIV-1 lacks determinants for pathogenicity as well as for replication in vivo. Our data indicate that (i) the replication defect can be recovered in vivo by mutations in the env gene, without an associated pathogenic phenotype, and (ii) nef can function in the HXB/LW clone as a pathogenic factor that does not enhance HIV-1 replication in the thymus. Furthermore, the HXB/LW virus may be used to study mechanisms of HIV-1 nef-mediated pathogenesis in vivo.

Animals↗
PubMed2001

Increased heat-escape/cold-seeking behavior following hypertonic saline injection in rats.

We examined the effect of hypertonic saline injection on heat-escape/cold-seeking behavior in desalivated rats. Rats were exposed to 40 degrees C heat after normal (154 mM NaCl, control) or hypertonic saline (2,500 mM NaCl) injection (1 ml/100 g body wt). The rats received a 0 degrees C air for 30 s when they entered a specific area in an experimental box. Core temperature (T(c)) surpassed 40 degrees C in both conditions when 0 degrees C air was not available. Hypertonic saline injection produced a lower baseline T(c) than control [36.9 +/- 0.2 and 37.9 +/- 0.2 degrees C (means +/- SE), P < 0.05] and a greater number of 0 degrees C air rewards during the 2-h heat with lower T(c) at the end (48 +/- 1 and 34 +/- 2, 37.6 +/- 0.1, and 37.3 +/- 0.1 degrees C in the control and hypertonic saline injection trial, respectively, P < 0.05, n = 6). However, T(c) was similar (37.7 +/- 0.2 and 37.6 +/- 0.4 degrees C in the control and hypertonic saline injection trial, n = 5) when 0 degrees C air was automatically and intermittently (35 times) given during the heat. Rats augment heat-defense mechanisms in response to osmotic stress by lowering the baseline T(c) and increasing heat-escape/cold-seeking behavior.

Animals↗
PubMed2001

Phosphorylation of p190 on Tyr1105 by c-Src is necessary but not sufficient for EGF-induced actin disassembly in C3H10T1/2 fibroblasts.

p190 RhoGAP is a tyrosine phosphorylated protein that contains an N-terminal GTP binding domain, a middle domain (MD) that mediates interaction with p120 RasGAP and a C-terminal GTPase-activating protein (GAP) domain that is specific for the &Rgr; family of small GTPases. Evidence is accumulating to suggest that p190 participates in actin cytoskeleton rearrangements that occur following transformation by v-Src or stimulation by growth factors, and that tyrosine phosphorylation of p190 by Src influences these processes. The current study was performed to establish whether p190RhoGAP directly participates in epidermal growth factor-induced actin stress fiber disassembly and how c-Src is involved in this process. Our results support a model in which the p190 MD negatively regulates the activity of the GAP domain and that c-Src phosphorylation of Y1105 is necessary, but insufficient on its own, for actin stress fiber disassembly.

Actins↗
PubMed2001

Tracheobronchial tumor cast formation and pneumothorax.

A 34-year-old white man was admitted to the hospital for progressive respiratory difficulty, recurrent left pneumothorax, and a diagnosis of aplastic left lung. Further evaluation, including bronchoscopy and CT scan, demonstrated a cast-forming tracheobronchial obstructing tumor. Surgical resection of the tumor through the left chest with left lower lobectomy resolved his symptomatology. Improved ventilation with an open airway led to expansion of the left upper lobe. The pathologic diagnosis remained controversial as to a definite designation and was primarily descriptive: spindle cell proliferation with myxoid and collagenized stromal benign tumor. However, the extent of this rubbery tumor cast and the ability to remove it intact illustrate the tenacity of the structure and the very unusual nature of a cast of the entire tracheobronchial system on the left side.

Adult↗
PubMed2001

The NAD(P)H:quinone oxidoreductase 1 gene polymorphism and lung cancer: differential susceptibility based on smoking behavior.

We conducted a hospital-based case-control study of 814 lung cancer patients and 1123 controls to examine the association of the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene polymorphism with lung cancer susceptibility. Using PCR-RFLP genotyping assay techniques, we analyzed DNA samples to detect the variant forms of the NQO1 gene in exon 6 on chromosome 16q. We examined the relationship between lung cancer odds and NQO1 genotypes after adjusting for age, gender, and smoking behavior using generalized additive modeling. We found no overall association between NQO1 genotypes and lung cancer susceptibility, regardless of age, gender, family history of cancer, or histological cell type. However, our data demonstrated that in both former and current smokers, there was an association between NQO1 genotypes and lung cancer susceptibility that was dependent upon cigarette smoking duration and smoking intensity. For both current and former smokers, smoking intensity was more important in predicting cancer risk than smoking duration for all of the genotypes. Among former smokers, individuals with the T/T genotype were predicted to have a greater cancer risk than those with the C/C genotype for smoking durations up to 37 years. The predicted cancer risk for former smokers with the C/T versus T/T genotype depended on both smoking intensity and smoking duration. Our results support the concept that differential susceptibility to lung cancer is a function of both an inheritable trait in NQO1 metabolism and individual smoking characteristics.

Adult↗
PubMed2001

The interaction between microsomal epoxide hydrolase polymorphisms and cumulative cigarette smoking in different histological subtypes of lung cancer.

Microsomal epoxide hydrolase (mEH) is involved in the metabolism of environmental and tobacco carcinogens. Smaller studies found inconsistent results in the relationship between mEH polymorphisms and lung cancer risk. We investigated the two polymorphisms of mEH in 974 Caucasian lung cancer patients and 1142 controls using PCR-RFLP techniques. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. There was no overall relationship between mEH genotypes and lung cancer risk. The adjusted odds ratio (OR) of the very low activity genotype versus that of other genotypes combined was 1.00 [95% confidence interval (CI), 0.74-1.34]. However, gene-environment interaction analyses revealed that the ORs decreased as cumulative smoking (defined as square root of pack-years) increased. When pack-years = 0, the OR was 1.89 (95% CI, 1.08-3.28). When pack-years = 28.5, the OR was 1.00 (95% CI, 0.76-1.32), and when pack-years = 80, the OR decreased to 0.65 (95% CI, 0.42-1.00). When cases were stratified according to histological subtypes, the interaction between mEH genotype and cumulative smoking was statistically significant (P < 0.01) for the 222 squamous cell carcinoma cases, whereas it was not significant (P = 0.18) for the 432 adenocarcinoma cases. In conclusion, cumulative cigarette smoking plays a pivotal role in the association between mEH polymorphisms and lung cancer risk, altering the direction of risk (in the case of the very low activity genotype) from a risk factor in nonsmokers to a relatively protective factor in heavy smokers.

Adult↗
PubMed2001

[A clinical analysis of 798 cases of M protein positive patients].

OBJECTIVE: To improve the understanding of the diseases with positive M protein by analyzing 798 cases, so as to reduce the failure and error of diagnosis. METHODS: The relations of diseases with the types of the disease and age and sex of the patients were analyzed. The presenting symptoms of multiple myeloma(MM) and non-MM were compared. The difference of Ig content among each type of MM and the characteristics of M protein in non-MM were also studied. RESULTS: In 798 cases with positive M protein, there were 648 cases of MM (81.2%) and 34 cases of Waldenstrom's macroglobulinemia (WM) (4.3%). The remaining 116 cases (14.5%) were benign or secondary monoclonal gammopathies. The average age of the patients was 58.3 years, and there was no difference of disease incidence between men and women. There was a marked difference between MM and non-MM in the presenting symptoms which were mainly lumbago and bone pain in MM but fever, weight loss and fatigue in non-MM. 648 cases of MM included 290 cases of IgG type (44.8%), 143 of IgA type (22.1%), 138 of light chain type (21.3%), 45 of IgD type (6.9%), 30 of non-secretion type (4.6%) and 2 of double-clonal type (0.3%). There was no marked distinction between kappa and lambda chain except in IgD type. The average M protein content of 116 cases of benign or secondary monoclonal gammopathies was (11.3 +/- 6.5) g/L. 55 of the 116 cases were monoclonal gammopathy of undetermined significance (MGUS), which accounted for 6.9% of all the cases. 35 cases were non-Hodgkin's lymphoma (NHL) (4.4%). CONCLUSION: M protein was mainly discovered in MM; it may also be discovered in MGUS, NHL, WM and other diseases. It is essential to have a better understanding of these diseases.

Adult↗
PubMed2001

[The value of medical thorascopy].

OBJECTIVE: To study the practicality and feasibility for a physician to diagnose and treat pleural diseases through thoracoscopy. METHODS: To perform open thoracoscopy on 345 patients with a fibrobronchoscope or a hard thoracoscope under local anesthesia and evaluate the safety and tolerance of patients during the operation. RESULTS: (1) Determination of etiology: in 92.7% (227/245 cases) of pleural effusion cases, 75.0% (69/92) of pneumothorax cases, etiologic causes have been determined and 8 cases of pleural tumors were diagnosed. (2) Therapeutic effectiveness: the response rate of malignant pleural effusions was 78.4% (80/102 cases), the cure rate of pneumothorax was 81.5% (75/92 cases) and for empyema, the cure rate was 92.9% (26/28 cases). (3) SAFETY: during operation the ECG, SaO(2), BP, R, P of 98 patients did not show important changes. In 345 patients, 4.3% (15/345) complained a fransceis cheot stiffin. 7% (24/345) showed sinus tachycardia. CONCLUSIONS: (1) Through thoracoscopy, we can observe the whole pleural cavity and can take biopsy specimen under direct observation. It is a good method to get the etiological diagnosis in cause-underdetermined pleural diseases. (2) It is effective and practical to treat difficult pleural effusion, the obstinate pneumothorax, or one that is not suitable for thoracic surgery. (3) It is safe and simple to apply the thoracoscopy under local anesthesia.

Adolescent↗
PubMed2000

CD154 variant lacking tumor necrosis factor homologous domain inhibits cell surface expression of wild-type protein.

X-linked hyper-IgM (XHIM) syndrome is an immunological disorder resulting from mutations in the CD154 gene. Some mutations occur in splicing sites and result in transcripts encoding wild-type and mutant proteins. These mutants lack the tumor necrosis factor homologous (TNFH) domain and consequently fail to trimerize. Given that the TNFH domain is responsible for trimerization, one may predict that the TNFH mutant can not participate in the assembly of wild-type CD154. Thus, it was puzzling why these patients exhibit XHIM phenotype, presumably resulting from a lack of functional CD154. One possibility is that the TNFH mutant exhibits a dominant negative effect over the wild-type protein. To investigate this, we coexpressed the wild-type protein and a TNFH mutant and examined the biochemical and functional properties of the resulting CD154 products. We demonstrate that despite the lack of the TNFH domain, the TNFH mutant can associate with the wild-type protein. Furthermore, such an association compromises the ability of the wild-type protein to mature onto the cell surface. These results provide a mechanism for the defect of CD154 in XHIM patients producing both wild-type and TNFH variants and suggest that besides the TNFH domain, the stalk region participates in the assembly of CD154 trimers.

CD40 Ligand↗
PubMed2000

Association of dietary antioxidants on the severity of gastritis in a high risk population.

PURPOSE: This study is to examine the role of dietary antioxidant intake on the severity of gastritis at the baseline in an intervention study, Chemoprevention of Gastric Dysplasia.METHODS: The Chemoprevention of Gastric Dysplasia is an intervention study conducted in the towns of Pasto and Tuquerres, Colombia. A 79-item food frequency questionnaire was administered to 1,219 subjects at baseline. Endoscopic screening for precancerous gastric lesions was performed in all subjects by biopsy and histologic diagnosis. Subjects without adequate diagnostic material (n = 18) and subjects identified as histologically normal (n = 12) or with gastric cancer (n = 4) were excluded from these analyses. Analysis of Variance on logarithm-transformed data was conducted on dietary antioxidants and the stages of gastritis (atrophic gastritis, intestinal metaplasia, and gastric dysplasia).RESULTS: After adjusting for age, body mass index, smoking status, year of education, total calorie intake, and H-pylori infection status, dietary vitamin C and vitamin E were found to be inversely associated with the severity of gastritis (p < 0.05). Decreased dietary alpha-carotene was found to be marginally associated with gastric dysplasia. Data were then stratified by town where subjects were recruited. The trends for the observed associations were apparent for dietary alpha-carotene, vitamin C and E. However, the association was significant only for vitamin C in Pasto. Compared to subjects with atrophic gastritis, subjects diagnosed with gastric dysplasia have an approximately 15% lower intake of vitamin C.CONCLUSIONS: This study confirmed the protective effect of specific dietary antioxidants on the severity of gastritis. Dietary vitamin C, and to a lesser extent, dietary vitamin E are potentially important for the prevention of gastric cancer.

Journal Article↗
PubMed2000

Modulation of HIV-1 replication by a novel RhoA effector activity.

The RhoA GTPase is involved in regulating actin cytoskeletal organization, gene expression, cell proliferation, and survival. We report here that p115-RhoGEF, a specific guanine nucleotide exchange factor (GEF) and activator of RhoA, modulates HIV-1 replication. Ectopic expression of p115-RhoGEF or Galpha13, which activates p115-RhoGEF activity, leads to inhibition of HIV-1 replication. RhoA activation is required and the inhibition affects HIV-1 gene expression. The RhoA effector activity in inhibiting HIV-1 replication is genetically separable from its activities in transformation of NIH3T3 cells, activation of serum response factor, and actin stress fiber formation. These findings reveal that the RhoA signal transduction pathway regulates HIV-1 replication and suggest that RhoA inhibits HIV-1 replication via a novel effector activity.

Amino Acid Sequence↗
PubMed2000

Distinct mechanisms of STAT phosphorylation via the interferon-alpha/beta receptor. Selective inhibition of STAT3 and STAT5 by piceatannol.

Interferon-alpha (IFNalpha) can activate several members of the signal transducers and activator of transcription (STAT) transcription factor family, a process that requires the tyrosine kinases Jak1 and Tyk2. Here we provide evidence that IFNalpha-mediated activation of various STAT proteins is regulated by distinct mechanisms. Piceatannol, previously reported as a Syk/ZAP70-specific kinase inhibitor, selectively inhibits the tyrosine phosphorylation of STAT3 and STAT5, but not of STAT1 and STAT2. This inhibition is paralleled by the loss of Jak1 and IFNAR1 tyrosine phosphorylation in response to IFNalpha, whereas Tyk2 and IFNAR2 tyrosine phosphorylation is unaffected. Last, the IFNalpha-induced serine phosphorylation of STAT1 and STAT3 is not inhibited by piceatannol but is sensitive to the Src kinase-specific inhibitor PP2. Thus, our results not only demonstrate that the IFNalpha/beta receptor utilizes distinct mechanisms to trigger the tyrosine phosphorylation of specific STAT proteins, but they also indicate a diverging pathway that leads to the serine phosphorylation of STAT1 and STAT3.

Cell Line↗
PubMed2000

Human skeletal myosin heavy chain genes are tightly linked in the order embryonic-IIa-IId/x-ILb-perinatal-extraocular.

Myosin heavy chain (MyHC) is the major contractile protein of muscle. We report the first complete cosmid cloning and definitive physical map of the tandemly linked human skeletal MyHC genes at 17p13.1. The map provides new information on the order, size, and relative spacing of the genes. and it resolves uncertainties about the two fastest twitch isoforms. The physical order of the genes is demonstrated to contrast with the temporal order of their developmental expression. Furthermore, nucleotide sequence comparisons allow an approximation of the relative timing of five ancestral duplications that created distinct genes for the six isoforms. A firm foundation is provided for molecular analysis in patients with suspected primary skeletal myosinopathies and for detailed modelling of the hypervariable surface loops which dictate myosin's kinetic properties.

3' Untranslated Regions↗
PubMed2000

Characterization of a virtually full-length human immunodeficiency virus type 1 genome of a prevalent intersubtype (C/B') recombinant strain in China.

A molecular epidemiology study was conducted among more than 100 human immunodeficiency virus type 1 (HIV-1) subtype C seropositive intravenous drug users (IDUs) from China. Genotyping based on the envelope C2V3 coding region revealed the highest homology of the most prevalent virus strains circulating throughout China to subtype C sequences of Indian origin. Based on these results, a virtually full-length genome representing the most prevalent class of clade C strains circulating throughout China was directly amplified from peripheral blood mononuclear cells of a selected HIV-infected IDU and subcloned. Sequence analysis identified a mosaic structure, suggesting extensive intersubtype recombination events between genomes of the prevalent clade C and (B')-subtype Thai virus strains of that geographic region. Recombinant Identification Program analysis and phylogenetic bootstrapping suggested that there were 10 breakpoints (i) in the gag-pol coding region, (ii) in vpr and at the 3' end of the vpu gene, and (iii) in the nef open reading frame. (B')-sequences therefore include (i) several insertions in the gag-pol coding region; (ii) 3'-vpr, the complete vpu gene, and the first exons of tat and rev; and (iii) the 5' half of the nef gene. Breakpoints located in the vpr/vpu coding region as well as in the nef gene of 97cn54 were found at almost identical positions of all subtype C strains isolated from IDUs living in different areas of China, suggesting a common ancestor for the C/B' recombinant strains. More than 50% of well-defined subtype B-derived cytotoxic T-lymphocyte epitopes within Gag and Pol and 10% of the known epitopes in Env were found to exactly match sequences within in this clade C/B' chimeric reference strain. These results may substantially facilitate a biological comparison of clade C-derived reference strains as well as the generation of useful reagents supporting vaccine-related efforts in China.

Amino Acid Sequence↗
PubMed2000

Effects of food deprivation on daily changes in body temperature and behavioral thermoregulation in rats.

Homeothermic animals regulate body temperature (T(b)) by using both autonomic and behavioral mechanisms. In the latter process, animals seek out cooler or warmer places when they are exposed to excessively hot or cold environments. Thermoregulation is affected by the state of energy reserves in the body. In the present study, we examine the effects of 4-day food deprivation on circadian changes in T(b) and on cold-escape and heat-escape behaviors in rats. Continuous measurement of T(b) during food deprivation indicated that the peak T(b) amplitude was not different from baseline values, but the trough amplitude continuously decreased after the onset of food deprivation. Cold-escape behavior was facilitated by food deprivation, whereas heat-escape behavior was unchanged. After the termination of food deprivation, the lowered T(b) returned to normal on the first day. However, cold-escape behavior was still facilitated on the third day after food reintroduction. Autonomic and behavioral thermoregulatory effectors are modulated in the face of food shortage so as to maintain optimal performance during the active period, whereas increasing energy conservation occurs during the quiescent phase.

Animals↗
PubMed2000

Measuring injection-site pain associated with vaccine administration in adults: a randomised, double-blind, placebo-controlled clinical trial.

BACKGROUND: Pain at the injection site is one of the most commonly-reported local reactions associated with administration of a vaccine, but it has not been quantified by a validated instrument for pain measurement. We conducted a randomised, double-blind clinical trial to evaluate the measurement characteristics of two commonly-used pain questionnaires, the McGill Present Pain Intensity (PPI) and the Brief Pain Inventory (BPI) Current Pain Question, in the assessment of intramuscular injection-site pain associated with vaccine administration. The PPI measures pain on a scale of 0 (no pain) to 5 (excruciating pain) and the BPI measures pain on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). METHODS: Two hundred healthy adults were randomised to one of the five regimens: tetanus and diphtheria toxoids adsorbed (Td), aluminum hydroxide adjuvant (alum), physiological saline, or one of the two licensed hepatitis A vaccines, VAQTA, or HAVRIX. Pain assessment was made at eight time-points over a 2-day period after injection. RESULTS: The differences in the time-averaged pain (+/- standard deviation) on the PPI were statistically significant between Td (0.58+/-0.59) and either saline (0.14+/-0.23) (p < 0.005) or alum (0.22+/-0.35) (p < 0.01). Reported time-averaged pain were significantly lower for VAQTA than HAVRIX (p = 0.028). Similar differences were observed for the BPI. CONCLUSIONS: Both instruments have sufficient discriminative validity to distinguish between different levels of injection-site pain in adults.

Adolescent↗