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Biomedical subjects

S Liu

Publications and source records attributed to S Liu.

At least 451 records · Page 25Linked to original sources
PubMed1999

New protective antigen of group A streptococci.

It is widely believed that the surface M protein of group A streptococci is the predominant surface protein of these organisms containing opsonic epitopes. In the present study, we identified a new surface protein, distinct from M protein, that evokes protective antibodies. A type 18 M-negative mutant was found to be both resistant to phagocytosis in human blood and virulent in mice. The wild-type strain, but not the M-negative mutant, was opsonized by antisera against purified recombinant M18 protein or a synthetic peptide copying the NH2-terminus of M18. However, antisera raised against a crude pepsin extract of the M-negative mutant opsonized both strains, indicating the presence of a protective antigen in addition to type 18 M protein. This antiserum was used to identify and purify a 24-kDa protein fragment (Spa, streptococcal protective antigen) that evoked antibodies that opsonized the M18 parent and the M-negative mutant. The results of passive mouse protection tests confirmed the presence of protective epitopes within Spa. The deduced amino acid sequence of a 636-bp 5' fragment of the spa18 gene showed no homology with sequences in GenBank. These studies reveal the presence of a new protective antigen of certain strains of group A streptococci that may prove to be an important component of vaccines to prevent streptococcal infections.

Amino Acid Sequence↗
PubMed1999

IL-1beta and IL-6 excite neurons and suppress nicotinic and noradrenergic neurotransmission in guinea pig enteric nervous system.

Conventional intracellular microelectrodes and injection of biocytin were used to study the actions of IL-1beta and IL-6 on electrical and synaptic behavior in morphologically identified guinea pig small intestinal submucous neurons. Exposure to nanomolar concentrations of either IL-1beta or IL-6 stimulated neuronal excitability. The excitatory action consisted of depolarization of the membrane potential, decreased membrane conductance, and increased discharge of action potentials. Excitatory action of IL-1beta was suppressed by the natural IL-1beta human receptor antagonist. Electrical stimulation of sympathetic postganglionic axons evoked inhibitory postsynaptic potentials (IPSPs), and stimulation of cholinergic axons evoked nicotinic fast excitatory postsynaptic potentials (EPSPs). Both kinds of synaptic potentials occurred in neurons with uniaxonal morphology believed to be secretomotor neurons. Either IL-1beta or IL-6 suppressed the noradrenergic IPSPs and the fast EPSPs, and the two acted synergistically when applied in combination. Suppression of the IPSP resulted from presynaptic inhibition of the release of norepinephrine from sympathetic nerves. The results suggest that the presence of either or both inflammatory cytokines will release the sympathetic brake from secretomotor neurons to the intestinal crypts and from nicotinic synapses in the integrative microcircuits, where norepinephrine is known to have a presynaptic inhibitory action. This, in concert with excitation of secretomotor neurons, may lead to neurogenic secretory diarrhea.

Animals↗
PubMed1999

Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1 assays to quantitate proliferation in breast cancer.

PURPOSE: To investigate the hypothesis that in vitro bromodeoxyuridine (BrDu) labeling might be superior to MIB-1 immunostaining for prognostic value, because it more selectively labels cells during the S phase. METHODS: Four hundred eighty-six patients with breast cancers (59% lymph node-negative, 41% lymph node-positive) surgically excised between 1988 and 1993 (median follow-up, 62 months) were evaluated for cellular proliferation using prospective in vitro BrDu uptake assays, retrospective mitotic indices, and MIB-1 labeling. RESULTS: MIB-1, BrDu labeling, and mitotic index-derived proliferation data were highly correlated. Each was similarly associated with most other markers of prognosis, although these relationships were not identical. By univariate analysis, nodal status was the most significant prognostic variable for all patients. Higher BrDu labeling index, MIB-1 immunolabeling, and mitotic index were also associated with shortened disease-free survival (DFS) and disease-specific survival for the entire patient group, as well as for node-negative patients. The association between cellular proliferation and survival was much weaker for node-positive patients. Multivariate models confirmed that nodal status, tumor size, and proliferation data predicted survival in all patients as well as those with node-negative disease, although MIB-1 was somewhat more closely associated with outcome than mitotic index or in vitro BrDu data. For patients with T1NOMO disease (n = 172), the only significant predictors of DFS were proliferation rate (mitotic index or MIB-1) and tumor grade. CONCLUSIONS: Proliferation rate predicts recurrence and survival in breast cancer. This effect is more pronounced in node-negative patients. In vitro BrDu data are not superior to MIB-1 and mitotic counting.

Adult↗
PubMed1999

Effects of overexpression of human GLUT4 gene on maternal diabetes and fetal growth in spontaneous gestational diabetic C57BLKS/J Lepr(db/+) mice.

During gestation, heterozygous C57BLKS/J-Lepr(db/+) mice develop spontaneous gestational diabetes mellitus (GDM), and the newborn fetuses are macrosomic compared with offspring from wild-type (+/+) mothers. To investigate the effects of the leptin receptor mutation on maternal metabolism and fetal growth during pregnancy, we studied +/+, db/+, and db/+ transgenic mice that overexpress the human GLUT4 gene two- to three-fold (db/+TG6). During pregnancy, fasting plasma glucose and hepatic glucose production were twofold greater in db/+ than +/+ mice, despite similar insulin levels. In skeletal muscle, insulin-stimulated tyrosine phosphorylation was decreased in pregnant +/+ mice, and even more so in db/+ mice: insulin receptor beta (IR-beta), +/+ 34%, db/+ 57% decrease, P<0.05; insulin receptor substrate 1 (IRS-1), +/+ 44%, db/+ 61% decrease, P<0.05; and phosphoinositol (PI) 3-kinase (p85alpha), +/+ 33%, db/+ 65% decrease, P<0.05. Overexpression of GLUT4 in db/+TG6 mice markedly improved glucose-stimulated insulin secretion, by 250%, and increased IRbeta, IRS-1, and p85alpha phosphorylation twofold, despite no change in concentration of these proteins. Plasma leptin concentration increased 40-fold during pregnancy, from 2.2+/-0.5 to 92+/-11 ng/ml and 3.6+/-0.1 to 178+/-34 ng/ml in +/+ and db/+ mice, respectively (P<0.01), but was increased to only 23+/-3 ng/ml in pregnant db/+TG6 mice (P<0.001). Maternal fat mass and energy intake were greater in db/+ mice, and fat mass was reduced by GLUT4 overexpression, independent of food intake. Fetal body weight was increased by 8.1 and 7.9% in db/+ and db/+TG6 mothers, respectively (P<0.05), regardless of fetal genotype, whereas fetuses from db/+TG8 mothers (four- to fivefold overexpression) weighed significantly less compared with pups from +/+ or db/+ mothers (P<0.05). These results suggest that the single mutant db allele effects susceptibility to GDM through abnormalities in insulin receptor signaling, defective insulin secretion, and greater nutrient availability. GLUT4 overexpression markedly improves insulin-signaling in GDM, resulting in increased insulin secretion and improved glycemic control. However, maternal hyperglycemia appears not to be the sole cause of fetal macrosomia. These data suggest that GDM is associated with defects in insulin receptor signaling in maternal skeletal muscle, and this may be an important factor provoking maternal and fetal perinatal complications.

Animals↗
PubMed1999

Changes in basketball shooting patterns as a function of distance.

The effect of distance on the accuracy and movement form in basketball shooting was examined using a dynamic systems approach. Five male and five female young adults (M = 26 yr.) with no basketball experience beyond regular physical education shot a basketball 20 times at each of eight distances from 5 to 40 ft. (Natural condition). Also, they pretended to shoot the ball 5 times at each of the eight distances, for a total of 200 shots each (Pretend condition). In the Natural condition, shooting accuracy significantly decreased as shooting distance increased. Across both conditions and across four body components (feet position, hand position, trunk rotation, and jump height), the participants shifted from one movement pattern to another 86.3% of the time as shooting distance increased. The distances at which the transitions occurred were significantly shorter in the Natural than the Pretend condition for the feet and hand components but not the trunk and jump-height components. These results indicated that shooting a basketball at increasing distances can be portrayed as a dynamic system characterized by abrupt changes in at least four body components at critical distances.

Adolescent↗
PubMed1999

2-pyridylthioureas: novel nonpeptide somatostatin agonists with SST4 selectivity.

Somatostatin [somatotropin release-inhibiting factor (SRIF)] is a cyclic tetradecapeptide that is a potent inhibitor of growth hormone (GH) secretion from the anterior pituitary. In addition to the inhibitory effects on GH-release, SRIF-14 and SRIF-28, a 28-amino acid form of SRIF extended from the N-terminal end, inhibit the release of a variety of other peptides including glucagon, insulin, and gastrin, and both peptides act as neurotransmitters and neuromodulators in the central nervous system and the periphery. SRIF exerts its potent inhibitory effects following binding to high affinity SRIF receptors (ssts) that have been identified on target tissues. The recent cloning of five ssts has confirmed that the effects of SRIF are mediated by a family of G protein-coupled receptors (sst1-5). Based on structural and pharmacological properties sst2, sst3, and sst5 belong to the SRIF1 receptor subclass, and the sst1 and sst4 subtypes comprise the SRIF2 subclass. The major difference between these two subclasses is that SRIF1 receptors bind octapeptide and hexapeptide SRIF-14 analogs with high affinity, while SRIF2 receptors bind these analogs with drastically reduced affinity. A screening program was initiated to identify a lead nonpeptide with affinity for sst1-5 receptors. The search focused on a scaffold with the following attachments: (1) a heteroaromatic nucleus to mimic the Trp8 residue, (2) a nonheteroaromatic nucleus to mimic Phe7, and (3) a primary amine or other basic group to mimic the Lys9 residue of SRIF-14. Using these criteria, a novel thiourea (NNC 26-9100, 17) was discovered as a structural lead. The key fragments in this compound are a heteroaromatic moiety (pyridine), an aromatic group, and a basic imidazole group connected through a thiourea scaffold. Compound 17 exhibited a Ki = 6 nM at sst4 receptors with a 100-fold sst4/sst2 selectivity and was shown to be a full agonist at this receptor subtype. This article will review the literature on the design and development of nonpeptide somatostatin receptor ligands and the therapeutic potential of these agents. Furthermore, our work on the development of 2-pyridylthioureas as sst4 receptor agonists will be described.

Animals↗
PubMed1999

[Using the method of two-color fluorescence in situ hybridization to detect aneuploidy of human sperms].

OBJECTIVE: To develop the method of two-color fluorescence in situ hybridization (FISH) assay and use it for detecting the aneuploidy frequency of human sperm chromosome. METHODS: Sperm sample was washed three times and the slides were prepared. The sperm heads were decondensed with dithiothreitol (DTT) and lithium diiodosalicylate (LIS). Then, the sperm nuclei were hybridized with biotin labeled alpha satellite X chromosome DNA probe (DXZ1) and digoxigenin labeled alpha satellite Y chromosome DNA probe (DYZ3). The hybridization signals were detected with CY3-Streptavidin, goat antistrepavidin for biotin labeled probe and with mouse antidigoxigenin, rabbit antimouse-FITC for digoxigenin labeled probe. RESULTS: Under the Nikon fluorescence microscope, the hybridization signals in the sperm heads were clearly visible. The sperm with one red hybridization signal was X chromosome sperm (X sperm), and the sperm with one green hybridization signal in the sperm head was Y chromosome sperm (Y sperm). In the case of two hybridization signals in one sperm head, the sperm should be a numerical abnormal one. By using two color FISH with one euchromosome probe and one sex chromosome probe, the sperm with same color of two hybridization signals in one sperm head could be identified as aneuploidy sperm or diploid sperm. CONCLUSION: The two color FISH assay may be used to detect the aneuploidy frequency of human sperms that were exposed to mutagents and environmental potential aneuoploidogenic agents.

Aneuploidy↗
PubMed1999

Effect of diclofenac sodium and dexamethasone on cultured human Tenon's capsule fibroblasts.

BACKGROUND AND OBJECTIVE: To investigate the effect of diclofenac sodium and dexamethasone on cultured human Tenon's capsule fibroblasts. MATERIALS AND METHODS: Two experiments were conducted. In the first experiment, fibroblasts were treated with either diclofenac sodium or dexamethasone at different concentrations, and the cell growth was quantified by using Coulter counter and hexosaminidase methods at 1, 3, 5, and 7 days after adding the drugs. In the second experiment, the cells were treated with each drug for 24 hours and then the cultures were switched to a drug-free medium. The cell growth was quantified at day 7 after removing the drugs from the medium. RESULTS: In the first experiment, inhibition of fibroblast growth in a dose-dependent manner was observed from days 1 to 7 in the cultures treated with each drug. The inhibitory was more pronounced in the diclofenac treated cultures. The typical spindle-shaped fibroblasts treated with higher concentrations of the drugs became spherical cells. In the second experiment, inhibition was not observed when the cultures were switched to a drug-free medium. The spherical cells recovered to spindle-shaped cells and proliferated as normal cells. CONCLUSION: Our results have shown that diclofenac sodium and dexamethasone can significantly inhibit human Tenon's capsule fibroblast growth in a cell culture model. The inhibitory effect was not observed when the cultures were switched after 24 hours to a drug-free culture medium.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Frequent chromosomal DNA unbalance in thyroid oncocytic (Hürthle cell) neoplasms detected by comparative genomic hybridization.

Thyroid oncocytic (Hürthle cell) neoplasms represent a distinct subset of follicular thyroid tumors characterized by abnormal accumulation of mitochondria, whose chromosomal abnormalities have never been systematically analyzed. We have used comparative genomic hybridization to investigate chromosomal DNA alterations in 11 thyroid oncocytic tumors (7 adenomas and 4 carcinomas). Unbalanced chromosomal DNA profiles were detected in 6 of 7 adenomas and 3 of 4 carcinomas, numerical chromosomal aberrations being the dominant feature. Comparative genomic hybridization findings are compatible with two separate groups of tumors with karyotypic abnormalities, one characterized by multiple chromosomal gains with polysomy of chromosomes 5 and 7, the other by loss of chromosome 2. Pathologic and clinical features were similar in the two groups with no difference observed between adenomas and carcinomas. Activating H-, K-, or N-Ras mutations are commonly detected in follicular adenomas and carcinomas of the thyroid gland. However, Ras mutational analysis demonstrated that only one of the tumors in this series, an oncocytic carcinoma with a balanced karyotype, had activating Ras mutations (at codon 13 of K-Ras). The lack of Ras mutations in the 9 oncocytic neoplasms exhibiting chromosomal aneuploidy indicates that numerical chromosomal abnormalities are independent of activating Ras mutations in oncocytic tumors.

Adenoma, Oxyphilic↗
PubMed1999

[Study on telomerase inhibition by ribozyme targeted to telomerase RNA component].

OBJECTIVE: To evaluate the possibility of using ribozyme technology for telomerase inhibition and cancer therapy. METHODS: A hammer head ribozyme (telomerase ribozyme, teloRZ) directed against the RNA component of human telomerase (hTR) was designed and synthesized to serve as a telomerase inhibitor. An in vitro transcription plasmid and a eukaryotic expression plasmid containing teloRZ gene were constructed. In vitro cleavage reaction was carried out by mixing the ribozyme RNA with DIG-labeled-hTR in different reaction conditions. Cleavage bands were detected by digoxin chemilumines- cent assay. The eukaryotic expression plasmid was inducted into HeLa cells by lipofectamine; the telomerase activities and bio-characteristics of HeLa cells were detected continuously. RESULTS: teloRZ showed a specific cleavage activity against the telomerase RNA component used as template. The in vitro cleavage ratio reached about 60%. The telomerase activities of cells expressing teloRZ dropped to eight times; the doubling times became longer and apoptosis ratios became higher with increasing population doublings (PDS); at 19-20 PDS 95% cells showed apoptosis. CONCLUSION: These findings support the potential use of this ribozyme against immortalized cancer cells.

Apoptosis↗
PubMed1999

[Inhibitory effect of glycyrrhizin on NF-kappa B binding activity in CCl4 plus ethanol induced liver cirrhosis in rats].

OBJECTIVE: To investigate the effects of Potenlini on nuclear factor-kappa B (NF-kappa B) binding activity in the livers of animals models with liver cirrhosis, and to delineate the molecular mechanism of the bioactivities of Potenlini. METHODS: Male SD rats were randomly allocated into a normal control group, a model control group, and a Potenlini group. Rats in the latter two groups were treated with CCl4 and Ethanol solution in order to induce chronic liver injury. Rats in Potenlini group were given Potenlini treatment at the same time. All rats were killed at the 9th week after CCl4 administration. Serum and liver specimens were collected, serum ALT activities and histological findings were assessed. Nuclear extracts from liver tissues were prepared and gel retardation assays were performed for the evaluation of NF-kappa B activity. RESULTS: (1) Serum ALT levels were significantly reduced in rats treated with Potenlini compared with those in rats of the model control group, which had dramatically increased ALT levels. (2) Histologically, liver steatosis and fibrosis were severe in the rats of the model group, but were significantly improved in rats of the Potenlini group. (3) NF-kappa B binding activity was markedly increased in the liver specimens taken from the rats of the model control group in comparison with the binding of normal livers, but the binding levels were nearly normal in the livers of the Potenlini group. CONCLUSION: Potenlini can inhibit the NF-kappa B binding activity in CCl4 and ethanol induced chronic liver injury, and that may partially be the mechanism by which Potenlini protects liver from hepatotoxin-induced liver injury and cirrhosis.

Alanine Transaminase↗
PubMed1999

Degradation of cardiac troponin I in serum complicates comparisons of cardiac troponin I assays.

BACKGROUND: Up to a 20-fold variation in serum cardiac troponin I (cTnI) concentration may be observed for a given patient sample with different analytical methods. Because more limited variation is seen for control materials and for purified cTnI, we explored the possibility that cTnI was present in altered forms in serum. METHODS: We used four recombinantly engineered cTnI fragments to study the regions of cTnI recognized by the Stratus(R), Opus(R), and ACCESS(R) immunoassays. The stability of these regions in serum was analyzed with Western blot. RESULTS: The measurement of several control materials and different forms of purified cTnI using selected commercial assays demonstrated five- to ninefold variation. Both the Stratus and Opus assays recognized the N-terminal portion (NTP) of cTnI, whereas the ACCESS assay recognized the C-terminal portion (CTP) of cTnI. Incubation of recombinant cTnI in normal human serum produced a marked decrease in cTnI concentration as determined with the ACCESS, but not the Stratus, immunoassay. Western blot analysis of the same samples using cTnI NTP- and CTP-specific antibodies demonstrated preferential degradation of the CTP of cTnI. CONCLUSIONS: The availability of serum cTnI epitopes is markedly affected by the extent of ligand degradation. The N-terminal half of the cTnI molecule was found to be the most stable region in human serum. Differential degradation of cTnI is a key factor in assay-to-assay variation.

Blotting, Western↗
PubMed1999

Development of record linkage of hospital discharge data for the study of neonatal readmission.

Computerized record linkage has been used increasingly in epidemiologic studies. We developed a multistage, deterministic matching algorithm using various combinations of key variables. Then, from the records for March 1, 1993, to March 31, 1996, contained in the discharge abstract database of the Canadian Institute for Health Information (CIHI), we examined the relation between length of hospital stay at birth and neonatal readmission. A combined use of province/territory of occurrence, 6-digit postal code of residence, date of birth and sex (step 1) matched 88.5% of 26,629 eligible neonatal readmission records with their birth records. Additional use of institution code and chart number or health card number combined with date of birth and sex (step 2 and step 3) increased the matching rate to 93.0%. Compared with the gold standard, step 1 correctly matched 94.4% of the records. We conclude that this deterministic matching algorithm is a feasible and convenient approach to data linkage for the study of neonatal readmission. The linkage strategy may also be helpful in epidemiologic studies of other short-term events

Algorithms↗
PubMed1999

Have diagnostic practices contributed to trends in leukemia incidence and mortality among Canadians?

OBJECTIVE: To outline the patterns and temporal trends in leukemia, regarding incidence and mortality, in Canada since 1970. DESIGN: A descriptive analysis of trends in incidence and mortality by age, sex, time period and leukemia subtype, using change-point modelling and log-linear regression. SETTING: Data from all provincial and territorial cancer registries. MAIN OUTCOME MEASURE: Incidence and mortality rate per population of 100,000. RESULTS: The overall age-adjusted incidence rates for all males and females increased from 12.3 and 7.3 per 100,000 in 1970-1972 to 14.6 and 9.0 in 1979-1981, then decreased to 13.2 and 8.3 in 1991-1993, respectively. The overall age-adjusted mortality rates decreased from 9.1 and 5.7 per population of 100,000 in 1970-1972 to 8.3 and 4.8 in 1993-1995 for males and females, respectively. The incidence of acute leukemias decreased between 1970 and 1993. A sharp increase in the incidence of chronic leukemias from 1978 to 1980 was observed in the older age group. Mortality rates also showed a small increase from 1979 to 1989 in seniors. CONCLUSION: The increase in the incidence of chronic leukemias among older subjects was probably due to improvements in diagnosis and changes in registration practices, whereas the decrease in the incidence of acute leukemias was probably a real change attributable to environmental factors. Further investigation is needed to clarify whether and to what extent diagnostic practices contributed to the increased detection of chronic leukemias among elderly Canadians.

Adolescent↗
PubMed1999

[Study on the inhibition of nude mice transplantation tumor growth by telomerase ribozyme].

OBJECTIVE: To explore whether telomerase ribozyme could inhibit the growth of nude mice transplantation tumor. METHODS: A xenograft human-nude mouse model was constructed. A total of 24 mice were divided into 4 groups, namely, the saline control(Group 1), the blank plasmid control(Group 2), the 20 microg/mouse/day p(XJ-neo-teloRZ)(Group 3) and the 30 microg/mouse/day p(XJ-neo-teloRZ)(Group 4). All plasmids were packaged by lipofectamine and used for subcutaneous, continuous infusions over 14 days. Tumor measurements and observations of animal behavior were recorded daily. On completion of the study, the mice were killed by cervical dislocation and their organs were removed, weighed, and stored in formaldehyde for histological examination. The telomerase activities of tumor tissues of each group were also detected. RESULTS: The telomerase ribozyme effectively inhibited the telomerase activities of tumor tissues and promoted the apoptosis of tumor cells. The in vivo studies showed a significant decrease in tumor size in mice treated with p(XJ-neo-teloRZ) when compared to the mice treated with controls. Furthermore, the in vivo effect of p(XJ-neo-teloRZ) was dose dependent. CONCLUSION: Telomerase ribozyme is a powerful telomerase inhibition agent; probably it could be effective in tumor gene therapy.

Animals↗
PubMed1999

Loss of TGFbeta, Apoptosis, and Bcl-2 in Erectile Dysfunction and Upregulation of p53 and HIF-1alpha in Diabetes-Associated Erectile Dysfunction.

Vasculogenic erectile dysfunction (ED) is associated with collagen replacement of the cavernosal smooth muscle, mediated by an increase in transforming growth factor (TGF)-production secondary to hypoxemia. We tested the hypothesis that human ED is the result of an increase in apoptosis of the cavernosal smooth muscle cells with replacement by collagen, mediated by the TGFbeta upregulation. We also examined the tissue for proteins associated with apoptosis. Human cavernosal tissue was procured from impotent men at the time of prosthesis insertion. Normal corpous cavernosum served as a control. The TUNEL assay was used to assess apoptosis. Immunohistochemistry staining was used to detect TGFbeta and Bcl-2 expression, while Western blot analysis was used to detect expression of Bcl-2, p53, and hypoxia-inducible factor (HIF)-1a. Immunohistochemistry showed downregulation of TGFbeta protein expression in the corpus cavernosum of men with ED. Apoptotic nuclei were noted in cavernosal smooth muscle from a potent man but were not found in cavernosal tissue from men with ED. To gain insight into the possible mechanism of apoptosis in men with ED, the proto-oncogene Bcl-2, a potential inhibitor of apoptosis, was examined. Both immunohistochemistry and Western analysis revealed the presence of Bcl-2 in the cavernosal nerve of a potent man but its absence in cavernosal tissue from men with ED. Thus, loss of Bcl-2 expression correlated with the loss of apoptosis. In contrast, Western blotting demonstrated upregulation of p53 and HIF-1a expression in the cavernosal tissues from the men with ED and diabetes. Male ED follows an active process characterized by a loss of TGFb expression, apoptosis, and Bcl-2 expression. However, there is upregulation of p53 and HIF-1a in men with diabetes. These data support the possibility of hypoxia-mediated ED in diabetes via upregulation of p53 and HIF-1a but does not substantiate a role for TGFbeta in ED.

Journal Article↗