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Biomedical subjects

S Lu

Publications and source records attributed to S Lu.

At least 217 records · Page 12Linked to original sources
PubMed1998

[A probe into the relationship between spasmodic dysphonia and laryngeal paralysis].

OBJECTIVE: To investigate into the relationship between spasmodic dysphonia and laryngeal paralysis. METHODS: The intrinsic laryngeal muscle potential was recorded with electromyography. Vocal cord movements were observed with a videostroboscope. Laryngeal paralysis was divided into mild, moderate, and severe degrees based on the potentials of intrinsic laryngeal muscles and on the status of vocal cord movements. RESULTS: In the past 12 years (from 1983 to 1994) 1300 cases were diagnosed as having mild, moderate, and severe laryngeal paralysis. Among them, there were 5 cases with laryngospasm including 3 mild, 1 moderate, and 1 severe case. CONCLUSION: The findings obtained from careful observation on these 5 cases of spasmodic dysphonia demonstrated that there existed certain relationships between laryngeal paralysis and spasmodic dysphonia. During the course of exacerbation or restoration of paralysis, spasmodic dysphonia might occur.

Adult↗
PubMed1998

Analysis of genetic diversity in Chinese sweetpotato [Ipomoea batatas (L.) Lam.] germplasm using DNA amplification fingerprinting.

The genetic diversity and evolutionary relationships in a representative sample of Chinese sweetpotato collection were assessed using the DNA amplification fingerprinting approach. DNA fingerprint profiles were developed for all 42 accessions tested. There were 19-26 bands for each accession and an average of 20.7 such bands were polymorphic. Chinese sweetpotato germplasm tested exhibited a high degree of genetic diversity. Phenetic analysis revealed five major clusters with the following components: (1) landraces from Guangdong Province, (2) landraces from Fujian province, (3) Chinese cultivars, (4) those closely related to Japanese sweetpotato cultivars, and (5) those closely related to the US sweetpotato cv. Nancy Hall. The genetic association observed between accessions was largely consistent with the known pedigree records. The DNA amplification fingerprinting may provide reliable insights into the domestication history of the sweetpotato crop and may be useful in germplasm enhancement.

Base Sequence↗
PubMed1997

Biologically active heteroarotinoids exhibiting anticancer activity and decreased toxicity.

A series of retinoids, containing heteroatoms in a cyclic ring and called heteroarotinoids, were synthesized, and their biological activity was evaluated using tissue culture lines that have measurable responses to trans-retinoic acid (t-RA). Transglutaminase (TGase) was assessed in the human erythroleukemia cell line (GMO6141A) as an indicator of differentiation and apoptosis. Proliferation was evaluated in a human cervical cell line, CC-1, which exhibits dose-dependent alterations in growth rate in response to treatment with trans-retinoic acid. Activation of nuclear retinoic acid receptors was determined in a reporter cell line established from CC-1. The reporter line, called CC-B, contains a reporter gene controlled by a retinoic acid responsive element (RARE) and a thymidine kinase (tk) promoter. Treatment of the CC-B line with the heteroarotinoids resulted in a dose-responsive and retinoid-dependent regulation of reporter gene expression. The heteroarotinoids exhibited activity in all assays and correlated in a statistically significant manner between assays. RARE transactivation activity in CC-B cells correlated with induction of TGase in GMO6141A (R = 0.96) and with a decrease in the growth rate of CC-1 cells (R = -0.90). The ability of the selected heteroarotinoids to induce differentiation, inhibit proliferation, and activate nuclear receptors demonstrates the chemotherapeutic potential of these agents. In view of the biological activity cited, an in vivo toxicity study was conducted on male B6D2F1 mice with three heteroarotinoids, namely 8 [(2E,4E,6E)-3,7-dimethyl-7-(1,2,3,4-tetrahydro-4,4-dimeth ylthiochroman-6-yl)-2,4,6-heptatrienoic acid], 10 [(2E,4E,6E)-3,7-dimethyl-7-(1,2,3,4-tetrahydro-4,4-dimeth ylchroman-6-yl)-2, 4,6-heptatrienoic acid], and 13 [(E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoic acid]. The mice were used with gavage of heteroarotinoids in corn oil [0.1, 0.2, 0.4, or 0.8 mg/kg] and with 0.01 or 0.05 mg/kg of TTNPB (5) [(E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1- propenyl]benzoic acid] as reference controls. The target organs affected in the mice by the three heteroarotinoids were those typically associated with t-RA (1) toxicity. The maximum tolerated dose (MTD) of 13 was 9.4 mg/kg/day, which was equal in toxicity to that of t-RA (1) and 1000-fold less toxic than TTNPB (5). The MTDs of 8 and 10 were 34 and 32 mg/kg/day, respectively, which is 3-fold less toxic than t-RA (1) and 3000-fold less toxic than TTNPB (5). The 3000-fold reduced toxicity, compared with only a 27% reduction biological activity of 8 and 10 with respect to that of TTNPB, observed in our assays indicates a good therapeutic ratio of these heteroarotinoids over the parent compound. The biological activity and reduced toxicity of these heteroartinoids demonstrate the potential efficacy as anticancer agents.

Animals↗
PubMed1997

Regulation of androgen-dependent prostatic cancer cell growth: androgen regulation of CDK2, CDK4, and CKI p16 genes.

Growth of prostatic epithelial cells is androgen-dependent; however, the mechanism of androgen action on cell growth is not well defined. We investigated whether androgen-dependent prostatic epithelial cell growth is mediated by androgen regulation of expression of genes controlling cell cycle progression. For this purpose, we used an androgen-dependent prostatic cancer cell line, LNCaP-FGC, as an in vitro model. We found that expression of CDK2 and CDK4 genes were up-regulated within hours of androgen treatment as detected in Northern and Western blot analyses. Kinase assay also confirmed that there was increased CDK2 kinase activity upon androgen stimulation. Moreover, androgen down-regulated expression of the cyclin-dependent kinase inhibitor p16 (MTS1, CDKN2) gene. The overall effects of these androgen actions result in an increased cyclin-dependent kinase activity and stimulation of the cell to enter S phase of the cell cycle, thereby enhancing cell proliferation. In contrast, an androgen-independent PC-3 cell line lost its response to androgen stimulation, and higher basal levels of CDK2, CDK4, and p16 genes were constitutively expressed in PC-3 cells. Collectively, these data suggest a possible signaling pathway of androgen in stimulating cell growth. These results also imply that in androgen-dependent prostate cancer, increased androgen receptor (AR) activity, resulting from AR gain-of-function mutations, AR gene amplification, or AR gene overexpression, malignantly stimulates proliferation of prostatic epithelial cells and constitutes one possible mechanism of androgen-dependent tumorigenesis.

Adenocarcinoma↗
PubMed1997

Factors controlling the competition among rotational and vibrational energy transfer channels in glyoxal.

The state-to-state transfer of rotational and vibrational energy has been studied for S1 glyoxal (CHOCHO) in collisions with D2, N2, CO and C2H4 using crossed molecular beams. A laser is used to pump glyoxal seeded in He to its S1 zero point level with zero angular momentum about its top axis (K' = 0). The inelastic scattering to each of at least 26 S1 glyoxal rotational and rovibrational levels is monitored by dispersed S1-S0 fluorescence. Various collision partners are chosen to investigate the relative influences of reduced mass and the collision pair interaction potential on the competition among the energy transfer channels. When the data are combined with that obtained previously from other collision partners whose masses range from 2 to 84 amu, it is seen that the channel competition is controlled primarily by the kinematics of the collisional interaction. Variations in the intermolecular potential play strictly a secondary role.

Journal Article↗
PubMed1997

Regulation of the expression of the tissue transglutaminase gene by DNA methylation.

We have investigated the role of DNA methylation in the regulation of the expression of the human tissue transglutaminase gene. Studies on the methylation of the transglutaminase promoter in normal and neoplastic human cells demonstrated that the promoter is methylated in vivo and hypomethylation of the promoter is correlated with constitutive gene expression. Demethylation of the promoter in vivo by treatment of the cells with 5-azacytidine increased transglutaminase expression and hypermethylation of the promoter in vitro suppressed its activity. These studies suggest that alternations in DNA methylation may be one of the mechanisms regulating the tissue-specific expression of the tissue transglutaminase gene.

Base Sequence↗
PubMed1997

Screening of HIV-1 Env glycoproteins for the ability to raise neutralizing antibody using DNA immunization and recombinant vaccinia virus boosting.

HIV-1 envelopes from two series of primary isolates (from Swedish patients 5 and 6), from JR-FL and BaL (prototypic monocyte/macrophage tropic viruses) and from HXB-2 (a prototypic T-cell-line-adapted virus), have been screened for their ability to elicit neutralizing antibody to HIV-1. Rabbits were primed by gene gun inoculation with plasmids expressing secreted monomeric (gp120) and oligomeric (gp140) forms of each Env. After four to six DNA immunizations administered over a 1-year period, rabbits were boosted with 10(8) plaque-forming units of a mixture of seven recombinant vaccinia viruses which express chimeric gp140 Envs (primary clade B sequences in a IIIb-related BH10 backbone). Neutralizing antibodies were assayed against two T-cell-line-adapted viruses (MN and IIIb), two non-syncytium-inducing (NSI) and two syncytium-inducing (SI) primary isolates, and two HIV-1-NL4-3-recombinants with patients 5 or 6 Envs (NL4-3/5A, NL4-3/6C). The DNA priming and recombinant vaccinia virus boosting raised low titers of neutralizing antibody in 10 of 19 rabbits. The highest titers of neutralizing activity (approximately 1:150 for MN) were raised in rabbits DNA primed with Envs from Swedish patients 5. These sera cross neutralized IIIb and MN but did not neutralize the primary isolates or the NL4-3 recombinant with the homologous 5A Env. Sera from rabbits primed with the HXB-2 Env DNA were, for the most part, type-specific for neutralization of IIIb. In one of three assays, sera from rabbits primed with plasmids expressing the JR-FL and BaL had possible low titer neutralizing activity for two NSI, but not two SI, primary isolates. Our results highlight the low immunogenic potential of the HIV-1 Env and demonstrate that different Envs have different potentials to raise low titer neutralizing antibody.

AIDS Vaccines↗
PubMed1997

Substance use and risky sexual behavior in female adolescents.

The purpose of this study was to elucidate the etiological pathways towards substance use and risky sexual behavior in female adolescent substance abusers. The study had three aims: (1) to determine the relations between behavioral dysregulation, negative affectivity, and childhood victimization with substance use and risky sexual behavior, (2) to determine whether these relations are mediated by internalizing symptomatology, antisocial behavior, and affiliating with an adult boyfriend; and (3) to determine whether age of menarche moderates the relation between the mediating variables and substance use and risky sexual behavior. Multiple behavioral, psychiatric interview, and self-report measures were used to index behavioral dysregulation, negative affectivity, childhood victimization, internalizing symptomatology, antisocial behavior, affiliation with adult boyfriends, substance use, and risky sexual behavior in 125 substance abusing female adolescents and 78 controls between the ages of 14-18 years. Structural equation modeling was used to determine the etiological pathways. Results indicated that behavioral dysregulation, negative affectivity, and childhood victimization were related to substance use and risky sexual behavior. Age of menarche was significantly correlated with affiliation with an older boyfriend and risky sexual behavior. Antisocial behavior mediated the associations between behavioral dysregulation, negative affectivity and childhood victimization with substance use and risky sexual behavior. Affiliation with an adult boyfriend was directly associated with substance use involvement and accounted for the relationship between chronological age and risky sexual behavior. Finally, late menarche enhanced the association between internalizing symptomatology and substance use involvement. The results highlight the importance of behavioral dysregulation, negative affectivity, and childhood victimization in predicting substance use and risky sexual behavior, as well as the finding that antisocial behavior and affiliation with an adult boyfriend may be etiologically important in predicting these outcomes. Therefore, from a prevention and treatment standpoint, behavioral and affective dysregulation, childhood victimization as well as antisocial behavior may serve as clinical 'gateways' for altering the developmental trajectory toward substance use and risky sexual behavior in high risk and substance abusing youth. For example, reducing dysregulation through behavior modification procedures that have been developed for conduct disordered children would appear to be a heuristic avenue of investigation emanating from the results obtained in this study.

Adolescent↗
PubMed1997

HIV-1 Env glycoproteins from two series of primary isolates: replication phenotype and immunogenicity.

Seven envelope regions from two series of patient isolates have been molecularly cloned and analyzed for replication phenotypes and immunogenicity. Growth potential was analyzed for env sequences substituted into an HIV-1-NL4-3 backbone (NL4-3/env recombinants). Immunogenicity studies were conducted on secreted monomeric (gp120) and oligomeric (gp140) forms of the Envs using Env-expressing plasmid DNAs for immunizations. The env regions of the patient isolates conferred a spectrum of replication kinetics and cytotropisms on the NL4-3/env recombinants. Both patient series included non-syncytium-inducing viruses with no ability to grow on T-cell lines, and highly syncytium inducing viruses which grew well on T-cell lines. These differences in growth potential did not correlate with the ability of the DNA-expressed Envs to raise antibody in rabbits. Rather, the relative immunogenicity of the Envs was patient and form specific. The Envs from patient 5 raised higher titers of antibody than the Envs from patient 6. For each primary Env, the gp120 form of the Env raised higher titers of antibody than the gp140 form. Thus, structural features of Env that affect replication do not necessarily affect the ability to raise antibody.

AIDS Vaccines↗
PubMed1997

Genetic isolation of a region of chromosome 8 that exerts major effects on blood pressure and cardiac mass in the spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) is the most widely studied animal model of essential hypertension. Despite > 30 yr of research, the primary genetic lesions responsible for hypertension in the SHR remain undefined. In this report, we describe the construction and hemodynamic characterization of a congenic strain of SHR (SHR-Lx) that carries a defined segment of chromosome 8 from a normotensive strain of Brown-Norway rats (BN-Lx strain). Transfer of this segment of chromosome 8 from the BN-Lx strain onto the SHR background resulted in substantial reductions in systolic and diastolic blood pressure and cardiac mass. Linkage and comparative mapping studies indicate that the transferred chromosome segment contains a number of candidate genes for hypertension, including genes encoding a brain dopamine receptor and a renal epithelial potassium channel. These findings demonstrate that BP regulatory gene(s) exist within the differential chromosome segment trapped in the SHR-Lx congenic strain and that this region of chromosome 8 plays a major role in the hypertension of SHR vs. BN-Lx rats.

Animals↗
PubMed1997

Localization of basement membrane-associated protein isoforms during development of the ocular surface of mouse eye.

The developmental localization patterns of collagen type IV alpha1-5 chains, laminin-1, laminin-5, and laminin alpha2 chain were analyzed in the embryonic mouse eye using isoform specific antibodies and immunofluorescence microscopy. Laminin-1 isoform and alpha1-2(IV) were ubiquitously expressed along the ocular surface basement membranes at a very early stage of eye development. Alpha3-5(IV) were first detected at later stages of development, and exhibited a variable distribution pattern along the ocular surface basement membrane. In contrast, expression of the laminin alpha2 chain was restricted to the conjunctival basement membrane, and was first detected during the same developmental period in which keratin K4-positive, differentiated conjunctival epithelial cells were observed. Although laminin-5 was uniformly expressed along the adult ocular surface basement membrane, during embryogenesis it was first incorporated into the conjunctival basement membrane structure. These data suggest that some of the laminin isoforms, including laminin alpha2 and laminin-5, may play a role in the formation of a conjunctival-type basement membrane. The temporal relationship between the localization of these molecules to the conjunctival basement membrane and the appearance of differentiated conjunctival epithelial cells suggests a role for external influence on the differentiation pathways of ocular surface epithelium.

Animals↗
PubMed1997

Biological assay for activity and molecular mechanism of retinoids in cervical tumor cells.

The composition and response of the retinoid signaling pathway in a human cell line (CC-1), representative of a low grade cervical carcinoma, were evaluated. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis demonstrated expression of cytoplasmic retinol binding protein, CRBPI, cytoplasmic retinoic acid binding protein, CRABPII, and nuclear retinoic acid receptors, RAR alpha, RARgamma, RXR alpha, and RXRbeta, but not CRABPI or RARbeta. This pattern is similar to that of the ectocervix. Activation of endogenous nuclear receptors was evaluated in a reporter subline of CC-1, called CC-B, containing a reporter gene controlled by a retinoic acid responsive element (RARE) and thymidine kinase promoter. Retinoid treatment of CC-B resulted in dose-dependent increases in reporter gene expression. Retinoids inhibited growth at concentrations greater than 100 nM. 9-cis retinoic acid (1 nM) significantly stimulated growth. Immunohistochemical analysis of CC-B organotypic cultures demonstrated a high level of epidermal growth factor receptor (EGF-R) expression that was decreased by retinoids. The degree of RARE transactivation induced by retinoids significantly correlated with the degree of inhibition of growth (R = -0.96) and EGF-R expression (R = -0.92). The dose-dependent and retinoid-specific responses of CC-1 at the molecular and biological levels demonstrate the utility of this reporter cell line for evaluation of retinoid activities.

Cell Division↗
PubMed1997

Potential for clinical use of viable pluripotent progenitor cells in blood bank stored human umbilical cord blood.

There are indications that a close HLA match may not be necessary when human umbilical cord blood (HUCB) is used to effect a hematopoietic transplant. This was first suggested in 1972 and was further supported by the ability of HUCB to produce mouse survival following lethal irradiation. In China multiple units of HLA unmatched HUCB was utilized successfully in children to effect transplants. A recent publication indicated that newborn rodent blood cells can engraft in adult mice across the non-H-2 [corrected] antigens. Furthermore, there recently have been successful transplants with 3 antigens mismatched HUCB. In this study HUCB was stored in polyolefin blood bank bags at 4 degrees C. The storage was similar to that used in routine blood banking. Clonogenic assays were performed at Day 1 and 21 utilizing various growth factors. Replating efficiency was determined on colonies obtained from cord blood that was stored (non-frozen) for 21 days. The functional ability of day 21 old HUCB was determined by its ability to produce survival of lethally irradiated mice. It was found that approximately two-thirds (62.5%) of single primary blast cell colonies in day 21 stored HUCB could generate various types of secondary colonies. In some instances the secondary colonies were counted as high as 42 total mean colonies per single primary colony. These blast cell colonies (CFU-BL) were able to form single and multi lineage colonies composed of virtually every hematopoietic cell types. Animal survival studies were utilized in an effort to determine possible functional ability and were successful in producing fifty-day survival in 54% of lethally irradiated SJL/J mice and 100% ALB/C mice. This study holds the potential of making HUCB available for purposes of marrow transplantation to all who need it. It could further remove most of the moral and ethical issues related to HUCB, reduce to a fraction the cost in providing stem cells for marrow transplantation and potentially allow HUCB to be handled by existing blood banks.

Animals↗
PubMed1997

Protective immunity induced by rotavirus DNA vaccines.

It is estimated that Group A rotavirus diarrhea causes as many as one million deaths per year in children worldwide, and effective vaccines will be essential for their control. Plasmid DNA vaccines encoding murine rotaviral proteins VP4, VP6, or VP7 were tested in adult BALB/c mice for their ability to induce immune responses and provide protection against rotavirus challenge. The vaccines were administered by inoculation into cells of the epidermis with an Accell gene gun. (Auragen, Inc., Middleton, WI, USA). Each vaccine elicited rotavirus-specific serum antibodies as measured by ELISA. Virus neutralizing antibodies were detected in mice receiving plasmid DNAs encoding for outer capsid proteins VP4 and VP7, but not for VP6, an inner capsid protein, and all of the vaccines generated virus-specific CTL responses. Each vaccine was effective in protecting mice against infection after homotypic rotavirus (100 ID50) challenge, showing reductions (P < 0.0002) in viral excretion measured over a 9 day period. Increased rotavirus-specific intestinal IgA antibodies were seen in vaccinated mice after rotavirus challenge, particularly in mice that received the VP6 DNA vaccine. This suggests that intracellular IgA-mediated neutralization may be involved in protective immunity induced by the VP6 DNA vaccine, and may represent a new mechanism for protection by DNA vaccines.

Animals↗
PubMed1997

SIV DNA vaccine trial in macaques: post-challenge necropsy in vaccine and control groups.

In this study we describe the histopathologic findings from nine macaques in a simian immunodeficiency virus (SIV) DNA vaccine trial evaluating the ability of a 5-plasmid DNA vaccine to protect against an uncloned SIVmac251 challenge (Lu et al., J. Virol. 1996, 70, 3978-3991). Three vaccinated and one control macaque developed disease and were euthanized in the first year following challenge. The other four vaccinated and one control macaque remained clinically normal and were euthanized at the end of the trial (60 weeks post-challenge). The necropsy data revealed that both diseased and clinically normal macaques had developed typical SIV-related lymphoid changes, inflammatory disorders and opportunistic infections. All animals had variable degrees of follicular and/or paracortical lymphoid hyperplasia suggesting immune activation. All but one vaccinated macaque and both control macaques had SIV-associated opportunistic infections. Within the small groups of animals, the ability to contain opportunistic infections was superior, and the overall lymphoid changes less severe, in the macaques that had received vaccine DNAs by three routes of inoculation (intravenous, intramuscular and gene gun) than in those that had received control DNAs or vaccine DNAs by gene gun only. In the future it will be important to further test how the route and method of DNA inoculation impact the efficacy of immunodeficiency virus vaccines.

Animals↗
PubMed1997

In vitro packaging of an infectious recombinant adeno-associated virus 2.

Adeno-associated virus 2 (AAV), a human parvovirus, has properties such as stable chromosomal integration, high infectivity and lack of known human pathogenicity, making it a potentially useful vector for human gene therapy. AAV requires a helper virus, such as an adenovirus, for optimal replication and packaging in mammalian cells. Although replication of the wild-type AAV genome has been demonstrated in vitro, packaging of infectious viral particles was not documented until now. In this study, we produced in vitro infectious recombinant AAV virions containing the neomycin resistance (NeoR) and the human CD-16 (FC gamma RIIIa) gene. Our in vitro packaging of AAV has the same characteristics as AAV produced in vivo and demonstrates the feasibility of developing a safe packaging method for AAV to be used in gene therapy.

DNA, Recombinant↗
PubMed1997

Chronically KIT-stimulated clonally-derived human mast cells show heterogeneity in different tissue microenvironments.

Human mast cell precursors arise in the bone marrow and circulate to different tissue microenvironments, where they develop distinct phenotypes that may be characterized by differential expression of the serine protease, chymase. The growth and development of mast cells is stimulated by mast cell growth factor, which is also known as kit ligand because its obligate receptor is KIT, the protein product of the c-KIT proto-oncogene. The in vivo influence of the KIT-kit ligand axis on the phenotype of human mast cells has not been determined. We used immunohistochemistry to detect in situ expression of tryptase and chymase by mast cells of a patient with urticaria pigmentosa and aggressive systemic mastocytosis, whose pathologic mast cells are clonally derived and chronically stimulated by KIT because they all contain the same point mutation causing constitutive activation of KIT. Mast cells in both spleen and skin expressed tryptase, but only in the skin did a majority of mast cells express chymase. We conclude that chronic stimulation of the KIT-kit ligand axis does not irrevocably commit mast cells to a chymase-positive or chymase-negative phenotype. These findings suggest that factors other than kit ligand predominate in determining mast cell phenotype.

Chymases↗