Biomedical subjects

S Zhao

Publications and source records attributed to S Zhao.

At least 289 records · Page 16Linked to original sources

PubMed1998

Disorderly CD44 gene expression in human cancer cells can be modulated by growth conditions.

Disorderly CD44 gene expression is a well-documented characteristic feature of tumour cells from cancers arising in many different organs of the human body. Molecular pathological studies have established that the pattern of the abnormal expression can differ according to the origin and the stage of the tumour. In this investigation it has been demonstrated that in some but not all tumour cell lines, which are undeniably and irreversibly malignant when inoculated in vivo, CD44 gene expression can still be modulated. In two cell lines, the pattern of CD44v expression was found to be affected by cell-to-cell and cell-to-substrate attachment. Expression was up-regulated by cell-substrate interactions, but only until cell-to-cell contact caused subsequent down-regulation of CD44v transcription. This information provides new opportunities for detailed investigation of the mechanisms of abnormal CD44 gene regulation in cancer and for exploring stage-related changes in the expression of this complex gene.

Antigens, Neoplasm↗

PubMed1998

Glioma prostaglandin levels correlate with brain edema.

The present study was designed to prospectively investigated the prostaglandin (PG) levels and extent of peritumoral edema in 30 cases of glioma by using methods of radioimmunoassay and imaging. Both TXB2 and 6-keto-PGF1 alpha levels in all glioma groups went up over that in the control group. TXB2 level and ratio of TXB2/6-keto-PGF1 alpha were markedly increased with the extent of tumor malignancy. Water concentration in anaplastic astrocytoma and glioblastoma were significantly elevated. Difference in TXB2 level and TXB2/6-keto-PGF1 alpha ratio among three edema grades were statistically significant. TXB2 level and ratio of TXB2/6-keto-PGF1 alpha were closely correlated with water concentration (r1 = 0.53, r2 = 0.72, P < 0.01). Our findings suggested that the metabolism of PG in glioma were in the state of disorder, and that the imbalance between PGI2 and TXA2 may be one of factors which affect the formation of peritumoral edema.

6-Ketoprostaglandin F1 alpha↗

PubMed1998

Imaging of intraperitoneal tumors with technetium-99m GSA.

99mTc labeled galactosyl serum albumin (GSA) has been used clinically as a receptor-binding agent for the assessment of liver function. The aim of this study was to investigate the usefulness of 99mTc-GSA in intraperitoneal (i.p.) tumor imaging. A tumor model was established by i.p. inoculating nude mice with human ovarian cancer cell SHIN-3, or colon cancer cell LS 180. Radiolabels were i.p. injected into the tumor-bearing mice and the biodistribution of radioactivity was examined. After administration, 99mTc-GSA rapidly accumulated in the tumor. The tumor uptake was 5.82-8.46 %ID/g from 30 min to 6 h after the injection. Radioactivity in the blood was very low, less than 0.3 %ID/g, resulting in high tumor-to-blood ratio. Tumors could be clearly seen by scintigraphic imaging. Accumulation of i.p.-injected 99mTc labeled human serum albumin (HSA) in i.p. tumors was similar to that of 99mTc-GSA, but radioactivity of 99mTc-HSA in the circulation was high, resulting in a significantly lower tumor-to-blood ratio. In conclusion, 99mTc-GSA, when i.p. injected, accumulated in i.p. tumors and cleared from circulation rapidly, which would make it useful for the imaging of i.p. tumors.

Animals↗

PubMed1998

Feasibility of imaging photodynamic injury to tumours by high-resolution positron emission tomography.

One early effect of the treatment of tumours by the new modality photodynamic therapy (PDT) is a reduction in tumour glucose levels. We have employed the widely used positron-emitting glucose analogue flurorine-18 fluoro-2-deoxy-D-glucose ([18F]-FDG), to determine whether, in principle, PDT-induced injury might be delineated non-invasively and quantitatively by positron emission tomography (PET). The scanner was of the high-density avalanche-chamber (HIDAC) type with a resolution of 2.6 mm. Subcutaneous T50/80 mouse mammary tumours, sensitised by haematoporphyrin ester, were illuminated by graded doses of interstitial 630 nm light. Thirty hours later, any remaining viable tumour was detected (a) by region-of-interest analysis of the PET images and (b) by gamma counting the excised tumour. PET measurements of % uptake of [18F]-FDG into tumour correlated closely with ex vivo gamma counting (slope=0.976, r2=0. 995), validating the in situ method. Uptake into untreated, control tumours was 3.8%+/-1.1% of the injected activity. Uptake of [18F]-FDG into treated tumours decreased by 0.7% for every 100 mm3 reduction in remaining viable histological volume. Outcome was further compared with that measured by (a) T2-weighted proton imaging on a 4.7-T magnetic resonance imaging (MRI) system and (b) histological analysis of subsequently sectioned tumours. PET using [18F]-FDG described the absolute volume of surviving tumour histological mass to the same degree as high-resolution MRI. The conclusion of these initial studies is that PET with [18F]-FDG, although non-specific, quantitatively described at early times the extent of tumour destruction by PDT.

Animals↗

PubMed1998

Further characterization of cyclophosphamide resistance: expression of CD95 and of bcl-2 in a CML cell line.

Drug resistance is a common cause of treatment failure in oncology. In addition to the resistance caused by over-expression of p-glycoprotein and similar molecules other mechanisms are involved in the selection or induction of drug resistant tumor cells. In this study, we characterized a CML cell line made resistant to cyclophosphamide (KBM7-B5-1803) further for the expression of apoptosis promoting and inhibiting molecules. We found that KBM7-B5-1803 has a 3 4-fold over-expression of the receptor CD95 (Fas/Apo-1) compared with the parent line. The regulation of CD95 by cytokines was comparable to other types of cells. Despite the inducibility and over-expression of CD95, CD95 failed to trigger apoptosis in both the parent and the drug resistant line. The drug resistant line has a particular pattern of the expression of bcl-2 family members: bcl-2 protein and message were expressed to a similar extent, however, compared with the parent line, the message for bclx short was decreased. P-glycoprotein was not expressed in either cell line. Taken together we show here in a leukemia cell line that the phenotype of cyclophosphamide resistance is associated with a particular pattern of apoptosis-related molecules.

Apoptosis↗

PubMed1998

Three-step tumor imaging with biotinylated monoclonal antibody, streptavidin and 111In-DTPA-biotin.

The purpose of this study was to test the three-step targeting of tumors in mice using biotinylated antibody, streptavidin and radiolabeled biotin. Nude mice bearing subcutaneous LS180 human colon cancer xenografts were intravenously administered with 200 microg of the biotinylated anti-Tn monoclonal antibody MLS128, and 2 days later they got intravenous injection of 50 microg of streptavidin. They were intravenously injected 1, 4 or 7 days later with 0.5 microg of 111In-diethylenetriamine pentaacetic acid (DTPA)-biotin. The tumor uptake, determined 2 h later, was 1.4, 0.5 and 0.6% injected dose/gram of tissue (ID/g), respectively, and the blood radioactivity was 1.0, 0.2 and 0.2% ID/g, respectively. When the interval between the streptavidin and radiolabeled biotin injections was prolonged from 1 day to 7 days, the tumor-to-blood ratio 2 h after injection of 111In-labeled biotin increased from 1.5 to 4.0. Clear tumor images were obtained as early as 2 h after injection of radiolabeled biotin. In conclusion, these preliminary data suggested that the three-step method using the streptavidin-biotin system would be applicable in an experimental mouse tumor model and provides images of tumors rapidly and clearly after injection of radiolabeled biotin.

Animals↗

PubMed1998

Effect of administration route and dose of streptavidin or biotin on the tumor uptake of radioactivity in intraperitoneal tumor with multistep targeting.

The effect of the administration route and dose of streptavidin or biotin on the biodistribution of radioactivity in multistep targeting was studied in nude mice bearing intraperitoneal (IP) colon cancer xenograft. The multistep targeting included a two-step method using biotinylated antibody and radiolabeled streptavidin and a three-step method with radiolabeled biotin based on the two-step method. A monoclonal antibody, MLS128, which recognizes Tn antigen on mucin, was biotinylated and injected intravenously (i.v.) or i.p. in nude mice bearing human colon cancer LS180 IP xenografts for pretargeting. In the two-step method, i.p.-injected streptavidin showed a higher tumor uptake and tumor-to-nontumor ratios than i.v.-injected streptavidin regardless of administration route of pretargeting. The tumor uptake of radiolabeled streptavidin was increased with a high dose of biotinylated antibody pretargeting, but decreased with an increasing dose of streptavidin. In the three-step targeting, i.p. injection also gave a higher tumor uptake of radiolabeled biotin than i.v. injection. In conclusion, i.p. administration of radiolabeled streptavidin or biotin resulted in more efficient IP tumor targeting with the multistep methods.

Animals↗

PubMed1998

Pulsatilloside C from the roots of Pulsatilla chinensis.

A new lupane-type triterpene saponin, pulsatilloside C (1), was isolated from the roots of Pulsatilla chinensis. Its structure was established to be 3beta,23-dihydroxylup-20(29)-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)- beta-D-glucopyranoside.

Carbohydrate Sequence↗

PubMed1998

Elevated levels of biologically active soluble CD40 ligand in the serum of patients with chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is an indolent lymphoproliferative disorder manifested by low growth fraction and prolonged survival of the malignant cells. The mechanisms that enable CLL cells to live longer and to resist apoptosis remain unclear. Because the malignant CLL cells express CD40 and Fas receptors, which can transduce cell-survival and cell-death signals, we examined the role of CD40 in the growth regulation of CLL cells and its interaction with Fas-mediated and fludarabine-induced apoptosis in vitro. Primary CLL cells underwent spontaneous apoptosis in culture, which was enhanced by exogenous human Fas ligand (FasL) or fludarabine. Exogenous CD40L rescued CLL cells from spontaneous apoptosis in a dose-dependent manner, and caused CLL cells to resist apoptosis induced by FasL or fludarabine. Patients' autologous plasma rescued CLL cells from spontaneous apoptosis, an effect that could be reversed with anti-CD40 ligand (CD40L) antibodies. The levels of soluble CD40 ligand in the sera of 51 CLL patients and 55 healthy donors were determined by enzyme-linked immunosorbent assay. The mean soluble CD40L level in normal donors was 0.29 ng/ml compared to a mean value of 0.80 ng/ml in CLL patients (P < 0.001). CD40L up-regulated bcl-X(L) mRNA but not bcl-2 in CLL cells within 3-6 h in culture. Our results demonstrated that serum of patients with CLL contained elevated levels of biologically active soluble CD40L, and that CD40L can prolong survival of CLL cells and mediate their resistance to FasL and fludarabine in vitro.

Adult↗

PubMed1998

Unbalanced expression of Fas and CD40 in mantle cell lymphoma.

B cells are characterized by the dual expression of CD40 and Fas receptors, which can mediate their survival and death, respectively. The balance between the dynamically opposing functions of these two receptors is important for B-cell selection, maturation and homeostasis. We found that mantle cell lymphoma (MCL) cells had a high level of CD40 and low or absent level of Fas, therefore favouring the CD40 cell survival pathway. Exogenous Fas ligand had no effect on MCL cells, whereas exogenous CD40 ligand enhanced their survival and rescued them from fludarabine-induced apoptosis. Our data raise the possibility that the prolonged survival of MCL cells in vivo may be explained by the unbalanced expression of Fas and CD40.

Apoptosis↗

PubMed1998

Coexpression of CD40 and CD40 ligand in B-cell lymphoma cells.

CD40 ligand (CD40L) is involved in the T-cell-dependent regulation of B-cell growth and survival and can rescue normal germinal centre B cells and several types of malignant B cells from apoptosis in vitro. We have previously reported that serum of patients with chronic lymphocytic leukaemia contained elevated levels of biologically active soluble CD40L (sCD40L). Whether an augmented CD40L pathway exists in patients with other types of B-cell lymphoid malignancies and the source of native sCD40L in these patients is currently unknown. Using a sensitive ELISA assay, soluble CD40L (sCD40L) was detected in the sera of both healthy individuals and patients with haematological malignancies; however, its level was significantly elevated only in patients with B-cell lymphomas (P<0.0001). Several types of malignant B cells coexpressed CD40 and CD40L proteins, and CD40L mRNA was detected in purified resting malignant B cells. The dual expression of CD40 and CD40L in B cells and the presence of native sCD40L in human serum suggest that a direct T-B-cell contact may not be required for CD40L delivery to B cells. This data raises the possibility that an autocrine cytokine loop involving CD40L may contribute to the growth regulation of benign and malignant B cells in vivo.

B-Lymphocytes↗

PubMed1998

Expression of c-Fos protein in the spinal cord after brachial plexus injury: comparison of root avulsion and distal nerve transection.

OBJECTIVE: Clinical reports indicate poor outcomes for avulsion injuries, compared with more peripheral nerve damage. These two different injuries may both affect gene expression in spinal neurons, and the changes in gene expression may be related to the types of injuries. METHODS: The brachial plexus of 48 adult male rats was lesioned by either root avulsion close to the spinal cord or distal nerve transection. The rats were quickly revived and remained awake until death at 30, 60, or 120 min after surgery. In rats with avulsive injuries, traumatic sites on the dorsal and ventral horns of the spinal cord were microscopically detected. Immunocytochemical analysis of the c-fos product was performed for the two experimental groups and for sham-treated control animals at the same survival times. RESULTS: An increase in Fos-like immunoreactivity (FLI) in cells of the spinal cord, at levels C4-T1, was detected at 30 min after nerve transection or root avulsion. The number of FLI-positive cells continued to increase at 60 and 120 min after the nerve injury (P=0.001). FLI-positive cells were compared at the C7 level, in laminae 1 and 2, 3 and 4, and 5 to 10, after the two injuries and were found to be more abundant after the avulsive injury (P=0.0001); furthermore, the number of FLI-positive cells increased with time (P=0.001). In a comparison of all levels, both experimental groups demonstrated significantly greater numbers of FLI-positive cells than did controls, and the group with nerve root avulsion showed significantly (P=0.0001) more FLI-positive cells than did the group with distal nerve transection. CONCLUSION: These results suggest that nerve root avulsion from the spinal cord leads to increased and prolonged expression of c-fos and, potentially, greatly increased transcription of new messages for recovery, survival, or cell death.

Animals↗

PubMed1998

A radioiodinated biocytin derivative for in-vivo applications.

Radioiodinated biocytin derivatives are potentially useful for multi-step tumour targeting using the avidin-biotin system. We synthesized a radioiodinated biocytin derivative and evaluated its properties in vivo. We labelled biocytin with 125I by coupling biocytin to radioiodinated N-succinimidyl 3-(tri-n-butyl-stannyl) benzoate, and assessed its binding to avidin and its biodistribution in normal and tumour-bearing mice. When the synthesized biocytin was incubated with immobilized avidin, more than 94% of the radioactivity was bound. However, after 2 h incubation in serum, only 40% of the radioactivity was bound to the avidin. The iodinated biocytin derivative was characteristically taken up by the liver and the kidneys when injected intravenously into mice. In mice bearing an intraperitoneal tumour xeno-graft, 125I-biocytin and 111In-biotin were co-injected intraperitoneally 4 h after the intraperitoneal administration of avidin, which accumulated in the intraperitoneal tumours. At 2 and 24 h, the tumour uptake of 125I-biocytin was 8.2 and 3.8% ID/g respectively, whereas that of 111In-biotin was 20.0 and 18.7% ID/g respectively. When radioiodinated, biocytin retains its binding capacity to avidin, and it localizes well with high tumour-to-normal tissue ratios early post-injection using the two-step method, but compared to 111In-biotin it is unstable. We conclude that the stability of the product in serum needs to be improved prior to in-vivo applications.

Animals↗

PubMed1998

Rhs elements comprise three subfamilies which diverged prior to acquisition by Escherichia coli.

The Rhs elements are complex genetic composites widely spread among Escherichia coli isolates. One of their components, a 3.7-kb, GC-rich core, maintains a single open reading frame that extends the full length of the core and then 400 to 600 bp beyond into an AT-rich region. Whereas Rhs cores are homologous, core extensions from different elements are dissimilar. Two new Rhs elements from strains of the ECOR reference collection have been characterized. RhsG (from strain ECOR-11) maps to min 5.3, and RhsH (from strain ECOR-45) maps to min 32.8, where it lies in tandem with RhsE. Comparison of strain K-12 to ECOR-11 indicates that RhsG was once present in but has been largely deleted from an ancestor of K-12. Phylogenetic analysis shows that the cores from eight known elements fall into three subfamilies, RhsA-B-C-F, RhsD-E, and RhsG-H. Cores from different subfamilies diverge 22 to 29%. Analysis of substitutions that distinguish between subfamilies shows that the origin of the ancestral core as well as the process of subfamily separation occurred in a GC-rich background. Furthermore, each subfamily independently passed from the GC-rich background to a less GC-rich background such as E. coli. A new example of core-extension shuffling provides the first example of exchange between cores of different subfamilies. A novel component of RhsE and RhsG, vgr, encodes a large protein distinguished by 18 to 19 repetitions of a Val-Gly dipeptide occurring with a eight-residue periodicity.

Amino Acid Sequence↗

PubMed1998

Effect of creatine supplementation on sprint exercise performance and muscle metabolism.

The aim of the present study was to examine the effect of creatine supplementation (CrS) on sprint exercise performance and skeletal muscle anaerobic metabolism during and after sprint exercise. Eight active, untrained men performed a 20-s maximal sprint on an air-braked cycle ergometer after 5 days of CrS [30 g creatine (Cr) + 30 g dextrose per day] or placebo (30 g dextrose per day). The trials were separated by 4 wk, and a double-blind crossover design was used. Muscle and blood samples were obtained at rest, immediately after exercise, and after 2 min of passive recovery. CrS increased the muscle total Cr content (9.5 +/- 2.0%, P < 0.05, mean +/- SE); however, 20-s sprint performance was not improved by CrS. Similarly, the magnitude of the degradation or accumulation of muscle (e.g., adenine nucleotides, phosphocreatine, inosine 5'-monophosphate, lactate, and glycogen) and plasma metabolites (e.g. , lactate, hypoxanthine, and ammonia/ammonium) were also unaffected by CrS during exercise or recovery. These data demonstrated that CrS increased muscle total Cr content, but the increase did not induce an improved sprint exercise performance or alterations in anaerobic muscle metabolism.

Adenine Nucleotides↗

PubMed1998

Monoclonal antibodies specific for rat relaxin. X. Endogenous relaxin induces changes in the histological characteristics of the rat vagina during the second half of pregnancy.

This study employed morphometric analysis to evaluate changes in the histological characteristics that accompany relaxin-induced growth and softening of the vagina during the second half of rat pregnancy. There were three treatment groups (N = 4/group). Five milligrams of a monoclonal antibody for rat relaxin, designated MCA1, were injected i.v. daily on days 12-21 of gestation to treatment group MCA1. Control groups received either 5 mg of monoclonal antibody for fluorescein (MCAF; monoclonal antibody control) or 0.5 ml PBS (vehicle control). Vaginas were removed on day 22 of pregnancy, fixed in 10% neutral-buffered formalin, and embedded in paraffin. Tissue sections (5 microm) were stained with Gomori's trichrome to visualize collagen, or orcein to visualize elastin. Measurements were performed with a light microscope equipped with a video camera connected to a computer. Within the vaginal stroma, the density of collagen fiber bundles was lower, the length of elastin fibers was shorter, and the cross-sectional area and wall thickness of arteries were greater in relaxin-replete control rats than in relaxin-deficient MCA1-treated rats. These relaxin-induced changes in the stroma appear to account, at least in part, for the hormone's softening effect on the vagina. Within the epithelium, there were approximately 2-fold more basal and mucus-secreting cells in relaxin-replete control rats than in MCA1-treated rats. The relaxin-induced accumulation of epithelial cells appears to contribute to vaginal growth. We conclude that relaxin plays a role in preparing the vagina as well as the cervix for rapid and safe delivery in pregnant rats.

Animals↗

PubMed1998

3'-end cDNA pool suitable for differential display from a small number of cells.

We have generated a 3' cDNA pool from the RNA of only 1000 or fewer cells by reverse transcription (RT) from an extended oligo(dT) primer with a 3' degenerate base and a second strand primer with four degenerate 3' bases, followed by PCR. Reproducible differential displays (DD) can be made from this essentially inexhaustible source of DNA. The method produced DD patterns that are comparable but not identical in band number and size distribution with those obtained by the original RT-DD technique. Northern blots performed with the excised bands verified altered gene expressions. The data indicate that this 3'-end cDNA pool can supplement current PCR-based methods of expression genetics. This pool of cDNA sequences also provides a reliable source for primer-specific gene amplifications.

Blotting, Northern↗

PubMed1998

Antibiotic resistance of Escherichia coli O157:H7 and O157:NM isolated from animals, food, and humans.

Antibiotic resistance was determined for 118 E. coli O157:H7 and 7 O157:NM isolates from animals, foods, and humans. Among the 125 isolates, 30 (24%) were resistant to at least one antibiotic and 24 (19%) were resistant to three or more antibiotics. Cattle isolates had the highest rate (34%) of antibiotic resistance. The seven resistant food isolates were all from ground beef. The most frequent resistance type overall was streptomycin-sulfisoxazole-tetracycline, which accounted for over 70% of the resistant strains. Two E. coli O157:NM isolates from cattle were resistant to six antibiotics: ampicillin, kanamycin, sulfisoxazole, streptomycin, tetracycline, and ticarcillin. Streptomycin was the most common antibiotic to which E. coli O157:H7 and O157:NM were resistant (29 out of 30 isolates), followed by tetracycline (26 isolates). This study suggests that E. coli O157:H7 and O157:NM have developed resistance to antibiotics. Research is needed to define mechanisms of antibiotic resistance in E. coli O157:H7 and to minimize the development of resistance.

Animals↗