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S Li

Publications and source records attributed to S Li.

At least 649 records · Page 36Linked to original sources
PubMed1999

LPD lipopolyplex initiates a potent cytokine response and inhibits tumor growth.

Our laboratory has recently developed a lipopolyplex consisting of DOTAP:cholesterol liposomes, protamine sulfate, and plasmid DNA (LPD) that provides improved systemic gene delivery compared with lipoplex following tail vein injection in mice. Because endothelial cells are the primary cells transfected in the lung, it was hypothesized that LPD might be an effective vector for gene therapy of pulmonary metastases. This hypothesis was examined by testing the efficacy of cytokine (IL-12) and tumor suppressor (p53) strategies for treatment of an experimental model of pulmonary metastasis in C57Bl/6 mice. Surprisingly, all LPD complexes including those containing an 'empty' plasmid provided a potent (>50% inhibition) and dose-dependent antitumor effect, compared with dextrose-treated controls. In addition, i.v. injections of LPD containing 'empty' plasmid also inhibited tumor growth in a subcutaneous model of C3 fibrosarcomma. The antitumor effect correlated well with a strong and rapid proinflammatory cytokine (TNF-alpha, IL-12 and IFN-gamma) response. Naked plasmid DNA did not elicit a cytokine response and the response required assembly of DNA into a lipoplex or the LPD lipopolyplex. Except for the heart, elevated levels of cytokine were observed in all organs (lung, liver, kidney and spleen) where LPD is known to have gene transfer activity. Methylation of immune-stimulatory CpG motifs in the plasmid component of LPD inhibited the proinflammatory cytokine response as well as the antitumor effect of LPD in both tumor systems. This suggests that i. v. administration of LPD elicits a systemic proinflammatory cytokine response that mediates the antitumor activity of the lipopolyplex. In addition, the antitumor activity was not observed in SCID mice suggesting a possible role for B or T lymphocytes in the antitumor response initiated by LPD. This represents the first demonstration that an intravenously administered cationic liposome-based nonviral vector can promote a systemic, Th1-like innate immune response. The immune adjuvant properties of LPD might prove to be suitable for delivering tumor-specific antigens in the context of DNA vaccination.

Animals↗
PubMed1999

Increased level and duration of expression in muscle by co-expression of a transactivator using plasmid systems.

Skeletal muscle is an attractive target for gene therapies to treat either local or systemic disorders, as well as for genetic vaccination. An ideal expression system for skeletal muscle would be characterized by high level, extended duration of expression and muscle specificity. Viral promoters, such as the cytomegalovirus (CMV) promoter, produce high levels of transgene expression, which last for only a few days at high levels. Moreover, many promoters lack muscle tissue specificity. A muscle-specific skeletal alpha-actin promoter (SkA) has shown tissue specificity but lower peak activity than that of the CMV promoter in vivo. It has been reported in vitro that serum response factor (SRF) can stimulate the transcriptional activity of some muscle-specific promoters. In this study, we show that co- expression of SRF in vivo is able to up-regulate SkA promoter-driven expression about 10-fold and CMV/SkA chimeric promoter activity by five-fold in both mouse gastrocnemius and tibialis muscle. In addition, co-expression of transactivator with the CMV/SkA chimeric promoter in muscle has produced significantly enhanced duration of expression compared with that shown by the CMV promoter-driven expression system. A dominant negative mutant of SRF, SRFpm, abrogated the enhancement to SkA promoter activity, confirming the specificity of the response. Since all the known muscle-specific promoters contain SRF binding sites, this strategy for enhanced expression may apply to other muscle-specific promoters in vivo.

Actins↗
PubMed1999

Effects of MK801 on evoked potentials, spinal cord blood flow and cord edema in acute spinal cord injury in rats.

OBJECTIVES: To determine whether MK801, an NMDA receptor antagonist, blocks glutamate excitotoxicity directly or via other mechanisms such as improving blood supply at the injury site in a rat model of spinal cord injury (SCI). In the present study, the effects of pre- and posttreatment with MK801 on axonal function, spinal cord blood flow (SCBF) and cord water content were studied after acute SCI in rats. METHODS: Somatosensory evoked potentials (SSEPs) and cerebellar evoked potentials (CEPs) were used to quantify electrophysiological function, and the hydrogen clearance technique and wet-dry weight measurements were used to measure SCBF and cord water content, respectively. Twenty rats received a 21 g clip compression injury of the cord at T1, and were then randomly and blindly allocated to either MK801 or saline groups. Each rat received an intravenous infusion of drug or saline four times during the experiment (16 min/infusion) with the first infusion (MK801 3 mg/kg) beginning 8 min pre-injury, and the other infusions (MK801 1. 5 mg/kg) at 1 h intervals after injury. Control experiments on uninjured rats were performed in 10 rats using the same procedure as above except the clip compression injury of the cord was omitted. RESULTS: In the MK801 groups with or without SCI, the amplitude of the evoked potential peaks, especially the SSEPs, was significantly lower than in the saline group. There were no differences in SCBF or cord water content between the MK801 and saline groups. CONCLUSION: Pre- and posttreatment with MK801 inhibits evoked potentials, but does not improve SCBF or cord edema after acute compression SCI in rats. For the first time it has been shown that MK801 produced a blockade of glutamate excitatory transmission in afferent pathways after SCI. Further work is required to determine whether this inhibition is reversible and related to neuroprotection and functional recovery after SCI.

Acute Disease↗
PubMed1999

Effects of ageing and dehydroepiandrosterone administration on pro-opiomelanocortin mRNA expression in the anterior and intermediate lobes of the rat pituitary.

There is still controversy about the influence of ageing on the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis in the rat. The first objective of the present study was to evaluate the influence of ageing on the activity of the HPA axis by measuring pituitary proopiomelanocortin (POMC, the precursor of ACTH and alphaH) mRNA levels in the anterior and intermediate lobes in young (50-55-day old) and aged (18-month-old) rats of both sexes. The second goal of the study was to evaluate the effect of 2.5 day administration of dehydroepiandrosterone (DHEA), a steroid precursor which has been shown to improve some ageing-associated deficits. In the young male anterior pituitary, DHEA induced a 17.5% increase in POMC mRNA levels. In aged males, anterior pituitary POMC mRNA levels were 22% lower than those detected in young animals. DHEA treatment produced a 26% increase, then completely restoring mRNA levels when compared to those found in young vehicle-treated males. In the young female, DHEA did not induce any changes in anterior pituitary POMC mRNA. In aged females a 24% reduction in the hybridization signal was observed. This reduction was completely reversed by DHEA which induced a 45% increase over the levels observed in vehicle-treated aged animals. In the intermediate lobe, the results were very similar to those obtained in the anterior lobe, although the observed effects induced by ageing and DHEA were less striking. These results together with previous ones indicating an age-related decrease in corticotropin-releasing hormone (CRH) neuronal activity suggest that ageing is associated with a decrease in HPA axis activity. They also demonstrate that a short-term DHEA treatment can exert a beneficial influence by reversing the decrease in pituitary POMC mRNA expression which occurs as a consequence of ageing.

Aging↗
PubMed1999

Upregulation of STAT1 protein in cells lacking or expressing mutants of the double-stranded RNA-dependent protein kinase PKR.

The interferon (IFN)-inducible double-stranded (ds) RNA-dependent protein kinase PKR plays a role in the regulation of gene expression through its capacity to phosphorylate the translation initiation factor eIF-2 and to inhibit protein synthesis. In addition to translational control, PKR has been implicated in the regulation of gene expression at the transcriptional level. In this regard, we have reported that PKR participates in IFN-and dsRNA-mediated signaling pathways by interacting with and modulating the transcriptional activity of the signal transducer and activator of transcription STAT1 [Wong, A.H.-T., Tam, N.W.N., Yang, Y.-L., Cuddihy, A.R., Li, S., Kirchhoff, S., Hauser, H., Decker, T. & Koromilas, A.E. (1997) EMBO J. 16, 1291-1304]. Here we report that the STAT1 protein is upregulated in cells lacking PKR (PKR-/-) and in cells expressing dominant negative PKR mutants. This upregulation is specific for STAT1 as increased expression is not observed for other STAT proteins. The inhibitory effect of PKR on STAT1 expression is exerted at the post-translational level because PKR-/- cells exhibit higher STAT1 protein stability than PKR+/+ cells.

Animals↗
PubMed1999

Experimental therapy of a platelet-activating factor antagonist (ginkgolide B) on photochemically induced thrombotic cerebral ischaemia in tree shrews.

1. The aim of the present study was to investigate the effects of a platelet-activating factor (PAF) antagonist (ginkgolide B; GB) on brain oedema, ion homeostasis, monoamine neurotransmitter disturbances in ischaemic penumbra and the neuroprotective mechanisms of the PAF antagonist. 2. Photochemically induced thrombotic cerebral ischaemia in tree shrews was used as the experimental model and changes in histopathology and the content of monoamine neurotransmitters (measured by a spectrofluorometer), water content (measured by a specific gravimetric method), sodium and calcium (measured by an atomic absorption spectrophotometer) in the penumbra were observed. 3. Results show that content of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) decreased in the penumbra, while 5-HT metabolite 5-hydroxyindole-3-acetic acid, sodium, calcium and water contents increased markedly (P < 0.01) after photochemical reaction. 4. In tree shrews treated with GB (5 mg/kg, i.v.) 6 h after photochemical reaction, cortical NA, DA and 5-HT contents recovered to control levels and water and calcium contents decreased significantly (P < 0.01). 5. The results suggest that PAF may play an important role in inducing calcium overload, brain oedema and secondary brain damage in penumbra and that GB produces its neuroprotective effects by inhibiting the pathological manifestation of PAF.

Animals↗
PubMed1999

Transplant surgery injury recruits recipient MHC class II-positive leukocytes into the kidney.

BACKGROUND: CD4 T cells, which are stimulated by the "indirect pathway" of antigen-presentation, participate in rejection. These T cells are sensitized by recipient major histocompatibility complex (MHC) class II-positive leukocytes that migrate into the transplant. Therefore, an important early step in rejection is the immigration of these recipient MHC class II-positive leukocytes into the renal transplant. The regulation of this early step is not understood. We now test the hypothesis that such leukocytes immigrate into the renal transplant in response to ischemic injury occurring during the transplant procedure. METHODS: We transplanted Brown Norway (BN) kidneys into F1 Lewis/Brown Norway (L/BN) recipients. The F1 recipients are tolerant to the parental BN antigens, and any infiltration of recipient MHC class II-positive leukocytes results from injury occurring during transplantation surgery. In addition, ischemia/reperfusion injury was also induced by temporarily occluding the native renal arteries for 30 minutes. Transplanted kidneys and native kidneys, which suffered ischemia/reperfusion injury, were studied by immunohistochemistry on days 3, 7, 14, and 28 after surgery. Staining by the new monoclonal antibody (mAb) OX62 and antibodies to MHC class II identified dendritic cells. In addition, the following monoclonal antibodies identified: gamma/delta T cells, V65; B cells, OX33; cells that may be macrophages, dendritic cells, or dendritic cell precursors, ED1 (+) and OX62 (-); and recipient class II MHC, OX3. RESULTS: After transplantation, the serum creatinine increased to 4 mg/dl and then decreased, which was consistent with reversible injury during transplantation and the absence of rejection. We found that the injury of transplantation itself resulted in the infiltration of recipient MHC class II-positive leukocytes into the transplanted kidney. This infiltrate peaked at days 7 to 14 after surgery. The inflammation was peritubular and patchy and involved cortex and outer medulla. Double staining for OX62 and OX3 identified some of the infiltrating leukocytes as dendritic cells. Other recipient leukocytes were MHC class II positive, ED1 positive, and OX62 negative. We also found that MHC class II leukocytes, including dendritic cells, infiltrated native kidneys injured by ischemia/reperfusion injury. CONCLUSION: To our knowledge, this is the first demonstration that injury to the kidney during transplantation recruits recipient MHC class II-positive leukocytes into the kidney. Some of these leukocytes are dendritic cells.

Animals↗
PubMed1999

A clinic-based mammography intervention targeting inner-city women.

OBJECTIVE: The objective was to evaluate the effect of a clinic-based intervention program on mammography use by inner-city women. DESIGN: A randomized controlled trial employing firm system methodology was conducted. SETTING: The study setting was a general internal medicine clinic in the university-affiliated county hospital serving metropolitan Seattle. PARTICIPANTS: Women aged 50 to 74 years with at least one routine clinic appointment (when they were due for mammography) during the study period were enrolled in the trial (n = 314). INTERVENTIONS: The intervention program emphasized nursing involvement and included physician education, provider prompts, use of audiovisual and printed patient education materials, transportation assistance in the form of bus passes, preappointment telephone or postcard reminders, and rescheduling assistance. Control firm women received usual care. MEASUREMENTS AND MAIN RESULTS: Mammography completion within 8 weeks of clinic visits was significantly higher among intervention (49%) than control (22%) firm women (p < .001). These effects persisted after adjustment for potential confounding by age, race, medical insurance coverage, and previous mammography experience at the hospital (odds ratio 3.5; 95% confidence interval 1.9, 6.5). The intervention effect was modified by type of insurance coverage as well as prior mammography history. Process evaluation indicated that bus passes and rescheduling efforts did not contribute to the observed increases in screening participation. CONCLUSIONS: A clinic-based program incorporating physician education, provider prompts, patient education materials, and appointment reminders and emphasizing nursing involvement can facilitate adherence to breast cancer screening guidelines among inner-city women.

Adult↗
PubMed1999

Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36.

Combining data from a genomic screen in 70 families with a high risk for prostate cancer (PC) with data from candidate-region mapping in these families and an additional 71 families, we have localized a potential hereditary PC-susceptibility locus to chromosome 1p36. Because an excess of cases of primary brain cancer (BC) have been observed in some studies of families with a high risk for PC, and because loss of heterozygosity at 1p36 is frequently observed in BC, we further evaluated 12 families with both a history of PC and a blood relative with primary BC. The overall LOD score in these 12 families was 3.22 at a recombination fraction (theta) of .06, with marker D1S507. On the basis of an a priori hypothesis, this group was stratified by age at diagnosis of PC. In the younger age group (mean age at diagnosis <66 years), a maximum two-point LOD score of 3.65 at straight theta = .0 was observed, with D1S407. This linkage was rejected in both early- and late-onset families without a history of BC (LOD scores -7.12 and -6.03, respectively, at straight theta = .0). After exclusion of 3 of the 12 families that had better evidence of linkage to previously described PC-susceptibility loci, linkage to the 1p36 region was suggested by a two-point LOD score of 4.74 at straight theta = .0, with marker D1S407. We conclude that a significant proportion of these families with both a high risk for PC and a family member with BC show linkage to the 1p36 region.

Aged↗
PubMed1999

Recombinant influenza A virus vaccines for the pathogenic human A/Hong Kong/97 (H5N1) viruses.

Recombinant reassortment technology was used to prepare H5N1 influenza vaccine strains containing a modified hemagglutinin (HA) gene and neuraminidase gene from the A/Hong Kong/156/97 and A/Hong Kong/483/97 isolates and the internal genes from the attenuated cold-adapted A/Ann Arbor/6/60 influenza virus strain. The HA cleavage site (HA1/HA2) of each H5N1 isolate was modified to resemble that of "low-pathogenic" avian strains. Five of 6 basic amino acids at the cleavage site were deleted, and a threonine was added upstream of the remaining arginine. The H5 HA cleavage site modification resulted in the expected trypsin-dependent phenotype without altering the antigenic character of the H5 HA molecule. The temperature-sensitive and cold-adapted phenotype of the attenuated parent virus was maintained in the recombinant strains, and they grew to 108.5-9.4 EID50/mL in eggs. Both H5N1 vaccine virus strains were safe and immunogenic in ferrets and protected chickens against wild-type H5N1 virus challenge.

Amino Acid Sequence↗
PubMed1999

Dual role of brain factor-1 in regulating growth and patterning of the cerebral hemispheres.

Brain factor-1 (BF-1) is a winged-helix (WH) transcription factor with a restricted pattern of expression in the neural tube. In the embryo, BF-1 is localized to the progenitor cells of the most rostral neural tube, the telencephalic neuroepithelium. Expression of BF-1 persists in the adult brain in the structures derived from the telencephalon, including the cerebral cortex, the hippocampus, the olfactory bulbs and the basal ganglia. Targeted disruption of the BF-1 gene in mice results in hypoplasia of the cerebral hemispheres. Proliferation of the telencephalic neuroepithelium is decreased and neuronal differentiation occurs prematurely. The forebrain of the BF-1 (-/-) mutant also displays dorsal-ventral patterning defects. Development of the ventral (basal) region of the telencephalon is more severely affected than the dorsal region. These anomalies are associated with the ectopic expression of BMP4 in the dorsal telencephalic neuroepithelium and the loss of shh in the ventral telencephalon. These results raise the possibility that BF-1 may modulate both progenitor cell proliferation and regional patterning by regulating the expression or activity of inductive signals which act on the telencephalic neuroepithelium.

Animals↗
PubMed1999

Prevalence of cerebral palsy in China.

BACKGROUND: A population-based study on the prevalence of cerebral palsy has not been previously carried out in China. The purpose of the present paper was to determine the overall and birthweight-specific prevalence of cerebral palsy. METHODS: A cross-sectional study of cerebral palsy was carried out among 388192 children aged <7 years in seven cities of Jiangsu province in China from May to July 1997. Information about birthweight was obtained from routine health care records. Doctors from township and city hospitals examined all eligible children and doctors at city level finally diagnosed all cases. All the doctors involved had taken part in a training programme held by Beijing Medical University in April 1997. RESULTS: The total prevalence of cerebral palsy was 1.6 per 1000 children and the birthweight-adjusted prevalence 2.8 per 1000 children (using Australia's neonatal survivors 1994 as a standard population). The overall neonatal mortality rate was 6.8 per 1000 live births, being highest (581.1 per 1000) in the 1000-1499 g birthweight group. The birthweight-specific cerebral palsy prevalence ranged from 0.8 per 1000 children in children weighing 3750-3999 g to 67.3 in children weighing 1500-1749 g. Children weighing 3500-3999 g at birth were at the lowest risk of cerebral palsy. In a given low birthweight group the prevalence of cerebral palsy in China was higher than that in developed countries even though this study was unable to include those who died at risk of, or with cerebral palsy. However, the prevalence of cerebral palsy at normal birthweight was almost the same as that in developed countries. In all, about 2% of all children were of low birthweight (<2500 g), with those weighing <1500 g accounting for about 0.02%. Children weighing <2500 g at birth contributed 24% of all cerebral palsy cases with 99% in the group 1500-2499 g. CONCLUSIONS: The prevalence of cerebral palsy for children aged <7 years is 1.6 per 1000 children. It is estimated that there are 310000 children with cerebral palsy in China and as the survival of low birthweight infants improves the prevalence of cerebral palsy will rise. Survival of low birthweight infants is lower in China than in developed countries and our findings suggest the survival quality of these Chinese children needs to be improved and that intrapartum and neonatal antecedents might play an important role in the aetiology of cerebral palsy compared to developed countries.

Age Distribution↗
PubMed1999

Mixed malignant germ cell tumor of the fallopian tube.

Immature teratomas of the fallopian tube are exceedingly rare with only three reported cases in the English literature. Reported here is a case of primary mixed malignant germ cell tumor of the fallopian tube composed of immature teratoma and yolk sac tumor.

Adult↗
PubMed1999

The septal chondromucosal island pedicle flap: anatomic study and clinical application.

A study was made of the facial regions of 10 fresh cadavers. The vascular anatomy of the perinasal region and the septum consistently confirmed the existence of a nasal alar basal artery and a nasal alar basal nerve to the septum. A new septal chondromucosal flap, supplied by the nasal alar basal artery and nerve, is proposed in this article. The composite flap can be used safely to restore partial or entire tarsoconjunctival defects of the upper or lower eyelid or combined defects of the upper and lower eyelid.

Adult↗
PubMed1999

Large scale screening of the mitochondrial DNA reveals no pathogenic mutations but a haplotype associated with multiple sclerosis in Caucasians.

We report the first large-scale screening of mitochondrial (mt) DNA in 77 Caucasian patients with relapsing-remitting or secondary progressive form of multiple sclerosis (MS) and in 84 Caucasian controls by using the method of restriction site polymorphism and haplotype analysis. No pathogenic mtDNA mutation was found in association with MS. However, mtDNA haplotypes K* and J* defined by the simultaneous presence of Ddel restriction sites at nucleotides 10,394 and 14,798 of the mtDNA in haplogroups K and J showed association with MS at a P-value of 0.001. A relative increase of MS patients compared to controls either with the J* or with the K* haplotype (+10,394Ddel/+14,798Ddel in haplogroup J or K) also was detected (each with a P<0.05). No distinct phenotypic characteristics of MS were observed when clinical data of patients with haplotypes K* or J* were analyzed. In addition to previous complete sequencing in several MS patients, the population screening of mtDNA presented here suggests that mtDNA point mutations are not likely to be involved in the pathogenesis of typical forms of MS. However, the mitochondrial genetic background (haplotype K* and J*) may moderately contribute to MS susceptibility. The reported association between MS and Leber's hereditary optic nerve atrophy, a disease caused by mtDNA point mutations preferentially occurring in haplogroup J, may be at least in part related to the overlapping mitochondrial genetic background of the two diseases.

Adult↗
PubMed1999

A simple and accurate coordinate transformation for a stereotactic radiotherapy system.

A global registration algorithm using only two CT slices was developed to transform target points known in the Brown-Roberts-Wells frame back to a CT-simulator coordinate system. The algorithm uses exact solutions to determine all of the points of interest based on BRW pins in the two CT-slices. In comparison with the algorithms based on individual slices, there is no requirement of digitization of BRW pins in every CT slice. There is no approximation (or linear interpolation) for determination of the target points that fell in between two CT slices. Results in 60 clinical cases demonstrate that the accuracy and precision of the isocentric positions are within the digitization uncertainty. Application of this global image registration can simplify the coordinate transformation in stereotactic radiation therapy.

Algorithms↗
PubMed1999

Establishing a quality control program for an automated dosimetry system.

Automatic dosimetry systems can provide instantaneous dose and dose-rate information during fluoroscopic procedures as well as long-term records of patient doses. For this information to be useful, it is necessary that the accuracy of such systems be maintained through a rigorous quality control program. Daily and weekly quality control checks were performed on a PEMNET automated dosimetry system to determine its stability and the value of such tests in a quality control program. Weekly tests included monitoring the accuracy of the measured doses under a variety of conditions. The results of the tests indicate possible improvements in test methodology and real and potential sources of system failure and provide a statistical basis for setting quality control limits for future system monitoring.

Biophysical Phenomena↗