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Biomedical subjects

S Lu

Publications and source records attributed to S Lu.

At least 19 recordsLinked to original sources
PubMed2001

Immune responses and protection obtained with rotavirus VP6 DNA vaccines given by intramuscular injection.

Intramuscular (i.m.) injection of murine VP6 DNA vaccines raised high titers of rotavirus-specific serum IgG and IgA antibodies in BALB/c mice. A Th1-like antibody response was generated based on the ratio of serum IgG2a to IgG1 antibodies. Rotavirus-specific serum IgA but not fecal IgA was detected in mice prior to rotavirus challenge. Partial protection against rotavirus challenge was achieved as measured by reduction of rotavirus antigen shedding in feces. A similar level of protection was found with a bovine rotavirus VP6 DNA vaccine against a murine rotavirus challenge, suggesting that heterologous protection can be obtained by immunizing with VP6 DNA vaccines. We did not directly test for cytotoxic T lymphocyte (CTL) activity, but in vivo depletion of CD8+ T cells in mice immunized with a murine VP6 DNA vaccine did not significantly change the duration of virus shedding or the pattern of protection obtained. This finding suggested that CD8+ CTL activity was not essential for the partial protection we obtained by i.m. immunization of mice with VP6 DNA vaccines.

Animals↗
PubMed2001

Susceptibility of lean and obese Zucker rats to tumorigenesis induced by N-methyl-N-nitrosourea.

To address the possible involvement of hyperinsulinemia in breast cancer development, we have examined the susceptibility of lean and obese Zucker rats to N-methyl-N-nitrosourea (MNU)-induced mammary cancer. Fifty-day-old female lean or obese Zucker rats received intraperitoneal (i.p.) injections of 37.5 or 20 mg/kg MNU, respectively. We showed in separate experiments that these doses produce similar levels of DNA methylation in the mammary epithelial cells of the lean and obese animals. Over the course of 29 weeks following MNU treatment, half of the lean rats developed carcinomas of the mammary gland, demonstrating that they are of intermediate susceptibility to mammary tumorigenesis. During this period, the obese rats developed hyperinsulinemia and insulin resistance as expected. Although palpable tumors developed at a similar rate in the lean and obese rats, only 10% of the obese animals developed mammary carcinomas. The obese rats, however, developed a high incidence (63.3%) of epidermal cysts that occurred mainly in the region of the mammary glands. A 13.3% incidence of colon carcinomas was also found in the obese rats. These results suggest that the development of hyperinsulinemia does not render the obese Zucker rats more susceptible to mammary gland carcinogenesis. Our observation of colon carcinomas in obese, but not lean rats, however, is consistent with evidence that hyperinsulinemia promotes colon cancer in rodents and humans.

Alkylating Agents↗
PubMed2001

Yersinia enterocolitica O9 as a possible barrier against Y. pestis in natural plague foci in Ningxia, China.

A survey of Yersinia spp, as related to plague control, was made in Haiyuan of Ganning loess plateau plague focus, Yanchi of Inner Mongolia plateau plague focus, and Yinchuan city, as a control area, in Ningxia, China. In Haiyuan, where the main plague reservoir was Mongolian ground squirrel (Citellus alaschanicus) living in the prairie, Y. enterocolitica O9 was frequently isolated from pigs, dogs, rodents living in and around houses, but only rarely from hare and Mongolian ground squirrel. In Yanchi, where the main plague reservoir was Mongolian gerbil (Meriones unguiculatus) living in the prairie and Y. pestis, which was isolated from rodents up to 1991, Y. enterocolitica O9 was sometimes isolated from pigs and rodents. In all areas, some strains of Y. enterocolitica O3 and Y. pseudotuberculosis serotypes 3 and 4b were also isolated from pigs, dogs, and from rodents. We propose that an epidemiological link exists between the prevalence of Y. pestis and Y. enterocolitica O9 in domestic and rodents living in these areas in China. The residential area in Haiyuan may be protected against Y. pestis by the domestic animals and rodents which acquired cross-protection against Y. pestis by infection with Y. enterocolitica O9, but this is not the case in the Yanchi district.

Animals↗
PubMed2001

Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry.

The ability to gain entry and resist the antimicrobial intracellular environment of mammalian cells is an essential virulence property of Mycobacterium tuberculosis. A purified recombinant protein expressed by a 1362 bp locus (mce1) in the M. tuberculosis genome promoted uptake into HeLa cells of polystyrene latex microspheres coated with the protein. N-terminus deletion constructs of Mce1 identified a domain located between amino acid positions 106 and 163 that was needed for this cell uptake activity. Mce1 contained hydrophobic stretches at the N-terminus predictive of a signal sequence, and colloidal gold immunoelectron microscopy indicated that the corresponding native protein is expressed on the surface of the M. tuberculosis organism. The complete M. tuberculosis genome sequence revealed that it contained four homologues of mce (mce1, mce2, mce3, mce4) and that they were all located within operons composed of genes arranged similarly at different locations in the chromosome. Recombinant Mce2, which had the highest level of identity (67%) to Mce1, was unable to promote the association of microspheres with HeLa cells. Although the exact function of Mce1 is still unknown, it appears to serve as an effector molecule expressed on the surface of M. tuberculosis that is capable of eliciting plasma membrane perturbations in non-phagocytic mammalian cells.

Antibodies, Bacterial↗
PubMed2001

A new algorithm for autoregression moving average model parameter estimation using group method of data handling.

A new algorithm for autoregresive moving average (ARMA) parameter estimation is introduced. The algorithm is based on the group method of data handling (GMDH) first introduced by the Russian cyberneticist, A. G. Ivakhnenko, for solving high-order regression polynomials. The GMDH is heuristic in nature and self-organizes into a model of optimal complexity without any a priori knowledge about the system's inner workings. We modified the GMDH algorithm to solve for ARMA model parameters. Computer simulations have been performed to examine the efficacy of the GMDH and comparison of the GMDH is made to one of the most accurate and one of the most widely used algorithms, the fast orthogonal search (FOS) and the least-squares methods, respectively. The results show that in some cases with noise contamination and incorrect model order assumptions, the GMDH performs better than either the FOS or the least-squares methods in providing only the parameters that are associated with the true model terms.

Algorithms↗
PubMed2001

Cloning, mRNA distribution, and functional expression of an avian counterpart of the chemokine receptor/HIV coreceptor CXCR4.

The chemokine signaling system, which coordinates the basal and emergency trafficking of leukocytes, presumably coevolved with the hematopoietic system. To study its phylogenetic origins, we used the open reading frame (ORF) of the human chemokine receptor CXCR4 as a genomic probe, since in mammals it is the most highly conserved chemokine receptor known. CXCR4 cross-hybridized to genomic DNA from mouse and chicken, but not zebrafish, Drosophila, or Caenorhabditis elegans. Accordingly, we cloned the corresponding chicken cDNA. The ORF is 359 codons long versus 352 for human CXCR4, and encodes a protein 82% identical to human CXCR4. In a calcium flux assay of receptor function, CHO-K1 cells stably transfected with the chicken cDNA responded specifically to human SDF-1, the specific ligand for CXCR4, but not to a panel of other chemokines tested at 100 nM. SDF-1 activated the cells in a dose-dependent manner (EC50 approximately 5 nM), whereas parental CHO-K1 cells did not respond. The CHO-K1 cell transfectants also bound 125I-SDF-1 specifically. Leukocytes from chicken peripheral blood expressed chCXCR4 mRNA and responded to human SDF-1 in a calcium flux assay with an EC50 similar to that for chCXCR4-transfected CHO cells, suggesting that this response is mediated by native chCXCR4. Analysis of chicken genomic DNA with the chicken cDNA as probe revealed a pattern consistent with a single copy gene, and the absence of any closely related genes. mRNA was detected in brain, bursa, liver, small and large intestine, embryonal fibroblasts, and blood leukocytes, but not in stomach or pancreas. These results, which identify the first functional non-viral, non-mammalian chemokine receptor, suggest that the origins of a functional chemokine system extend at least to birds and suggest that, as in mammals, CXCR4 functions in many avian tissues.

Amino Acid Sequence↗
PubMed2000

Isolation and characterization of a new chemokine receptor gene, the putative chicken CXCR1.

This study delineates the isolation and characterization of a novel chemokine receptor gene, the putative chicken CXC receptor 1 (cCXCR1). Using a human CXCR1 probe, we isolated several positive clones from a chicken genomic library. One of the clones contained a fragment of approximately 5000bp that hybridized strongly with the hCXCR1 probe. This fragment was sequenced and subjected to a variety of computer analyses. The open reading frame for this gene predicts a seven transmembrane domain protein with all the characteristics of a chemokine receptor and with 67% sequence homology to hCXCR1, 65% to hCXCR2 and also with considerable sequence homology to other human chemokine receptors such as hCXCR4 (50%), hCCR2 (49%) and hCCR1 (49%). However, the homology to a previously isolated potential G-protein-coupled receptor for chickens (AvCRL1) is only 47%. Using 5' RACE, two transcription initiation sites were identified suggesting the potential for the expression of two protein isoforms (I and II) in vivo. The promoter for the putative cCXCR1 contains a variety of consensus transcription factor binding elements that can potentially be involved in the expression of this chicken receptor upon stimulation by stress-inducing agents. RT-PCR analysis was used to determine the pattern of expression of the larger isoform (I) of this receptor in a variety of tissues. This form of the receptor is expressed primarily in the organs of the gastrointestinal tract, tissues that are frequently exposed to stress-inducing agents, but not in the central nervous system, tissues that are protected from insult by the blood barrier. Using the same RT-PCR approach we show that stress-inducing agents, such as 'first-hand' and 'second-hand' cigarette smoke components, tumor promoters and thrombin, differentially stimulate the expression of the isoform I in primary fibroblasts. Thrombin is an enzyme that plays many important roles in thrombosis, angiogenesis and wound healing and exposure to both cigarette smokes and/or to tumor promoters can lead to tumorigenesis. Therefore, upregulation of chemokines and their receptors by stress-inducing agents can confer highly regulated modulation of cellular responses to traumatic and pathological situations.

Amino Acid Sequence↗
PubMed2000

Protein kinase C-regulated dynamitin-macrophage-enriched myristoylated alanine-rice C kinase substrate interaction is involved in macrophage cell spreading.

Macrophage spreading requires the microtubule cytoskeleton and protein kinase C (PKC). The mechanism of involvement of the microtubules and PKC in this event is not fully understood. Dynamitin is a subunit of dynactin, which is important for linking the microtubule-dependent motor protein dynein to vesicle membranes. We report that dynamitin is a Ca(2+)/calmodulin-binding protein and that dynamitin binds directly to macrophage-enriched myristoylated alanine-rice C kinase substrate (MacMARCKS), a membrane-associated PKC substrate involved in macrophage spreading and integrin activation. Dynamitin was found to copurify with MacMARCKS both during MacMARCKS purification with conventional chromatography and during the immunoabsorption of MacMARCKS using anti-MacMARCKS antibody. Vice versa, MacMARCKS was also found to cosediment with the 20 S dynactin complex. We determined that the effector domain of MacMARCKS is required to interact with the N-terminal domain of dynamitin. MacMARCKS and dynamitin also partially colocalized at peripheral regions of macrophages and in the cell-cell border of 293 epithelial cells. Treatment with phorbol esters abolished this colocalization. Disrupting the interaction with a short peptide derived from the MacMARCKS-binding domain of dynamitin caused macrophages to spread and flatten. These data suggest that the dynamitin-MacMARCKS interaction is involved in cell spreading. Furthermore, the regulation of this interaction by PKC and Ca(2+)/calmodulin provides a possible regulatory mechanism for cell adhesion and spreading.

Adenosine Triphosphatases↗
PubMed2000

High-risk behaviors during incarceration in African-American men treated for HIV at three Los Angeles public medical centers.

OBJECTIVES: This paper describes research that examined the association between high-risk sexual and drug-using behaviors during incarceration and HIV infection for African-American men receiving HIV care at three public medical centers in Los Angeles County (LAC), California. METHODS: A case-control study was conducted in which 305 HIV-infected African-American men and 305 neighborhood controls, ages 20 to 49, were frequency-matched by age. RESULTS: After controlling for anal sex while not incarcerated, we found no association between anal sex during incarceration and HIV (odds ratio [OR], 1.1; 95% confidence interval [CI], 0.6-2.2). Among men with a history of incarceration (n = 332), the percentage reporting anal sex with men outside of incarceration (45%) was greater than those reporting anal sex while incarcerated (16%). Injection drug use (IDU) during incarceration was also not associated with HIV when controlling for IDU outside of incarceration (OR, 1.6; 95% CI, 0.5- 4.9). Increased time in jail or prison was associated with less HIV infection (p =.001). CONCLUSIONS: Although high-risk behaviors are more common in the community than in the incarcerated setting for this study group, incarcerated populations represent a high-risk group for whom access to prevention messages is limited. Periods of incarceration represent a unique opportunity to convey prevention messages that focus on high-risk behaviors outside the incarcerated setting.

Adult↗
PubMed2000

Photopolymerized, multilaminated matrix devices with optimized nonuniform initial concentration profiles to control drug release.

This paper describes a novel approach to obtain desired release profiles from diffusion-controlled matrix devices by employing nonuniform initial concentration profiles theoretically and experimentally. Theoretically, a model was developed to examine the effect of nonuniform initial concentration profiles on matrix release behavior, and an optimization technique was investigated to determine suitable nonuniform initial concentration profiles which provide desired release patterns. Experimentally, release rates of an organic dye from photopolymerized matrix devices were measured to test the application of these mathematical techniques and the efficacy of photolaminated matrices in approximating the optimized release behavior. All system parameters were measured by independent experiments, and the experimental release data agree very well with the computed results.

Acrylates↗
PubMed2000

Dynamic susceptibility contrast MR imaging: correlation of signal intensity changes with cerebral blood volume measurements.

Cerebral blood volume (CBV) maps derived from dynamic susceptibility contrast (DSC) magnetic resonance (MR) imaging provide valuable information regarding intracranial micro-hemodynamics and have been helpful in characterizing primary brain tumors and guiding stereotactic biopsy. Another parameter, the maximum signal drop (MSD) during the first pass of intravascular contrast bolus due to T2* effect, can also be measured directly without extensive post-processing and data manipulation. The purpose of our study is to determine whether MSD maps provide information similar to CBV maps in patients presenting with intracranial mass lesions. Twenty-nine patients with various intracranial mass lesions were studied with DSC MR imaging prior to stereotactic biopsy or volumetric resection. Maps of both CBV and MSD are calculated on a pixel-by-pixel basis and displayed as color overlays over the raw images. Relative CBV (rCBV) and MSD (rMSD) values were measured in regions of interest (ROIs) within areas of abnormality and compared. In addition, computer-generated noise was added to the data to estimate the sensitivity of each measurement to noise. The rMSD values were strongly correlated with rCBV values (r = 0.87, P = 0.0001). CBV values were much more sensitive to added noise than MSD values (P < 0.01). MSD maps derived from DSC MR imaging provide information similar to CBV maps in patients with intracranial mass lesions. MSD maps are a simple and reliable indicator of vascularity that can easily be incorporated into routine MR imaging.

Brain Neoplasms↗
PubMed2000

Changes in function of cardiac receptors mediating the effects of the autonomic nervous system in the muscular dystrophy (MDX) mouse.

Adrenergic and muscarinic receptor mediated effects on the force of contraction and heart rate were studied in the isolated left atria and right atria from dystrophin-deficient mdx mice and age matched C57BL/10ScSn (C57) mice, respectively. The pD(2) and pA(2) values of (-)-isoprenaline and CGP 20712A, respectively, were not different in left atria and right atria from mdx and C57 mice. (-)-Phenylephrine produced a small positive inotropic effect on mdx left atria that could be antagonized by prazosin, whereas in C57 left atria no positive inotropic response was seen. In contrast, the positive chronotropic effect of (-)-phenylephrine was reduced in right atria from mdx compared to C57 right atria (P<0.05). The potency and efficacy to carbachol in the presence of (-)-isoprenaline were higher in right atria from mdx compared to C57 mice (P<0.05), although in left atria only a greater efficacy was evident in mdx mice. In left atria, basal force of contraction and maximum Ca(2+)-induced increases in force of contraction were lower from mdx compared to C57 mice (P<0. 001 and P<0.05, respectively). In conclusion, marked changes were demonstrated in the function of alpha1-adrenoceptors and muscarinic receptors, but not in beta1-adrenoceptors in left and right atria from mdx mice.

Animals↗
PubMed2000

Age- and sex-associated changes in cardiac beta(1)-adrenoceptors from the muscular dystrophy (mdx) mouse.

Variations in beta(1)-adrenoceptor function due to age or sex were examined in the mouse model of Duchenne muscular dystrophy. Positive chronotropic and inotropic responses to (-)-isoprenaline and antagonist effects of CGP20712A were determined in isolated right and left atria from young (12 week) and old (12 month) male and old (12 month) female mdx mice and their age- and sex-matched C57BL/10ScSn (C57) mice. There was no difference in efficacy to (-)-isoprenaline when expressed as an increase in the rate of contraction or force of contraction as a percentage of Ca(2+)-induced increase respectively in right or left atria from age- and sex-matched mdx and C57. Old mdx males showed a decreased sensitivity to (-)-isoprenaline (P<0.05) and a reduced affinity to CGP 20712A (P<0.05) in both right and left atria compared with old C57 males. These same changes were also observed in left atria between old and young mdx males. A reduced efficacy to (-)-isoprenaline was also evident when young and old mdx males were compared. In contrast, in old females, mdx showed an increased affinity to CGP20712A in left and right atria (P<0.05), and an enhanced sensitivity to (-)-isoprenaline in right atria. Finally, in left atria, the maximum Ca(2+)-induced increase in force of contraction was lower in all mdx compared to their age- and sex-matched C57 (P<0.05). In conclusion, age- and sex-associated changes in beta(1)-adrenoceptor function and responses to calcium were demonstrated in cardiac muscle from mdx mice, with a marked deterioration in beta(1)-adrenoceptor function occurring with aging in male mdx being particularly evident.

Aging↗
PubMed2000

Alterations of basement membrane in di-isopropanolnitrosamine-induced carcinogenesis of the rat thyroid gland: an immunohistochemical study.

Alterations of basement membrane (BM) in di-isopropanolnitrosamine (DIPN)-induced carcinogenesis of the rat thyroid gland were examined by means of immunohistochemical localization of collagen type IV (CN-IV), laminin (LN), and fibronectin (FN) in prenodular and nodular thyroid lesions, correlating with the morphogenesis and proliferative activity of these lesions. Adult male rats of the Wistar strain were injected s.c. in the back with DIPN, and the thyroid glands were removed at the 15th and 30th week of treatment. Each of 133 thyroid lesions was histochemically analyzed. The follicular epithelial BM as revealed by CN-IV and LN was discontinued or completely lost during the progression of thyroid lesions from pre-nodular to nodular lesions and finally overt carcinomas. At the same time, the BM of vascular endothelial cells demonstrated a loss of dense capillary networks of follicles, a sinusoidal dilatation and, predominantly in carcinomas, development of interstitial-type blood vessels. However, FN, which was hardly stained in the normal thyroid tissue, was remarkably deposited in the interstitium of invasive carcinomas. These observations strongly suggested that alterations of BM structure play a key role in the morphogenesis of rat thyroid tumors, and that the expression of FN is an important step in the invasive growth of thyroid tumors.

Animals↗
PubMed2000

Recurrent chromosome changes in 62 primary gastric carcinomas detected by comparative genomic hybridization.

Comparative genomic hybridization (CGH) has been applied to detect recurrent chromosome alterations in 62 primary gastric carcinomas. Several nonrandom chromosomal changes, including gains of 8q (31 cases, 50%), 20q (29 cases, 47%) with a minimum gain region at 20q11. 2-q12, 13q (21 cases, 34%) with a minimum gain region at 13q22, and 3q (19 cases, 31%) were commonly observed. The regions most frequently lost included: 19p (23 cases, 37%), 17p (21 cases, 33%), and 1p (14 cases, 23%). High copy number gain (DNA sequence amplification) was detected in 6 cases. Amplification of 8q23-q24.2 and 20q11.2-q12 were observed in 3 cases. Gain of 20q and loss of 19p were confirmed by fluorescence in situ hybridization using corresponding bacterial artificial chromosomes (BAC) clones from those regions. The gain and loss of chromosomal regions identified in this study provide candidate regions involved in gastric tumorigenesis.

Adult↗
PubMed2000

Non-transferrin-bound iron is present in serum of hereditary haemochromatosis heterozygotes.

BACKGROUND: Hereditary haemochromatosis (HH) is a common autosomal recessive disease. Recently, HH heterozygosity has been identified as an independent risk factor for myocardial infarction and cardiovascular mortality. Iron may play an important role in atherogenesis by catalyzing peroxidation of low-density-lipoprotein (LDL), an essential step in atherogenesis. In iron overload conditions, non-transferrin-bound iron (NTBI) is found in serum, which can catalyze lipid peroxidation. We investigated whether sera of HH heterozygotes contain more NTBI than sera of normal controls. METHODS: In 27 treated HH homozygotes, 22 HH heterozygotes and 17 healthy control subjects, conventional parameters of iron status (serum iron, transferrin saturation, serum ferritin) were measured. NTBI was detected using HPLC after addition of nitrilotriacetic acid and pretreatment with cobalt. RESULTS: The conventional parameters of iron status were similar in the HH heterozygous group and the control group. NTBI was significantly higher in homozygotes compared to heterozygotes (1.79 micromol L-1 vs. 0.51 micromol L-1, 95% CI of the difference = 0.6-1.95, P < 0.001), and controls (1.79 micromol L-1 vs. - 0.3 micromol L-1, 95% CI of the difference = 1.36-2.81, P < 0.001). The difference in NTBI between the heterozygous subjects and control subjects was also significant (0.51 micromol L-1 vs. - 0. 3 micromol L-1, 95% CI of the difference = 0.05-1.57, P < 0.05). CONCLUSION: Phlebotomy treated HH homozygotes maintain a high and potentially harmful serum NTBI. HH heterozygotes have a higher serum NTBI than normal controls. The reported increased risk of cardiovascular events in heterozygous haemochromatosis may be explained by NTBI-catalyzed LDL peroxidation.

Cardiovascular Diseases↗