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Biomedical subjects

H Li

Publications and source records attributed to H Li.

At least 379 records · Page 21Linked to original sources
PubMed2001

Prolonged islet graft survival in NOD mice by blockade of the CD40-CD154 pathway of T-cell costimulation.

Allorejection and recurrence of autoimmunity are the major barriers to transplantation of islets of Langerhans for the cure of type 1 diabetes in humans. CD40-CD154 (CD40 ligand) interaction blockade by the use of anti-CD154 monoclonal antibody (mAb) has shown efficacy in preventing allorejection in several models of organ and cell transplantation. Here we report the beneficial effect of the chronic administration of a hamster anti-murine CD154 mAb, MR1, in prolonging islet graft survival in NOD mice. We explored the transplantation of C57BL/6 islets into spontaneously diabetic NOD mice, a combination in which both allogeneic and autoimmune components are implicated in graft loss. Recipients were treated either with an irrelevant control antibody or with MR1. MR1 administration was effective in prolonging allograft survival, but did not provide permanent protection from diabetes recurrence. The autoimmune component of graft loss was studied in spontaneously diabetic NOD mice that received syngeneic islets from young male NOD mice. In this combination, a less dramatic yet substantial delay in diabetes recurrence was observed in the MR1-treated recipients when compared with the control group. Finally, the allogeneic component was explored by transplanting C57BL/6 islets into chemically induced diabetic male NOD mice. In this setting, long-term graft survival (>100 days) was achieved in MR1-treated mice, whereas control recipients rejected their grafts within 25 days. In conclusion, chronic blockade of CD154 results in permanent protection from allorejection and significantly delays recurrence of diabetes in NOD mice.

Animals↗
PubMed2001

A role for hormone-sensitive lipase in glucose-stimulated insulin secretion: a study in hormone-sensitive lipase-deficient mice.

Endogenous lipid stores are thought to be involved in the mechanism whereby the beta-cell adapts its secretory capacity in obesity and diabetes. In addition, hormone-sensitive lipase (HSL) is expressed in beta-cells and may provide fatty acids necessary for the generation of coupling factors linking glucose metabolism to insulin release. We have recently created HSL-deficient mice that were used to directly assess the role of HSL in insulin secretion and action. HSL(-/-) mice were normoglycemic and normoinsulinemic under basal conditions, but showed an approximately 30% reduction of circulating free fatty acids (FFAs) with respect to control and heterozygous animals after an overnight fast. An intraperitoneal glucose tolerance test revealed that HSL-null mice were glucose-intolerant and displayed a lack of a rise in plasma insulin after a glucose challenge. Examination of plasma glucose during an insulin tolerance test suggested that HSL-null mice were insulin-resistant, because plasma glucose was barely lowered after the injection of insulin. Freshly isolated islets from HSL-deficient mice displayed elevated secretion at low (3 mmol/l) glucose, failed to release insulin in response to high (20 mmol/l) glucose, but had a normal secretion when challenged with elevated KCl. The phenotype of heterozygous mice with respect to the measured parameters in vitro was similar to that of wild type. Finally, the islet triglyceride content of HSL(-/-) mice was 2-2.5 fold that in HSL(-/+) and HSL(+/+) animals. The results demonstrate an important role of HSL and endogenous beta-cell lipolysis in the coupling mechanism of glucose-stimulated insulin secretion. The data also provide direct support for the concept that some lipid molecule(s), such as FFAs, fatty acyl-CoA or their derivatives, are implicated in beta-cell glucose signaling.

Animals↗
PubMed2001

Differential expression and distribution of syndecan-1 and -2 in the developing periodontium of the rat.

Cell surface proteoglycans are known to interact with adhesion molecules, growth factors and a variety of other effector molecules implying their central role in various aspects of cell-cell and cell-matrix interactions. To investigate the expression and distribution of the cell surface proteoglycans syndecan-1 and -2, the developing periodontal tissues of 3-, 5-, and 8-wk-old male Lewis rats, were stained by specific monoclonal antibodies against syndecan-1, or -2 core protein, using immunohistochemical techniques. The results demonstrated that syndecan-1 and -2 were expressed and distributed differentially in several compartments of the developing periodontal tissues at different ages. Expression of syndecan-1 was noted in areas of intense cellular activity such as the developing apical root tip of the tooth and at the crestal bone where new bone formation was taking place. In contrast, syndecan-2 expression and distribution did not exhibit the same patterns as syndecan-1. Syndecan-2 showed significant differences of distribution in hard tissues undergoing maturation at different ages. These findings indicate that syndecan-1 and -2 may have distinctive functions during morphogenesis, organogenesis and differentiation of the periodontium.

Animals↗
PubMed2001

Isoform-specific expression of VEGF-B in normal tissues and tumors.

Vascular endothelial growth factor B (VEGF-B), a member of the VEGF/PDGF family, is highly expressed in many tissues with two differentially spliced transcripts generating two secreted isoforms, VEGF-B167 and VEGF-B186. In this work, we have investigated the expression of VEGF-B in tissues and cell lines using techniques that can distinguish the two isoforms. The results showed that the VEGF-B167 isoform was predominantly expressed in most tissues, accounting for more than 80% of the total VEGF-B transcripts. The VEGF-B186 isoform was expressed at lower levels and only in a limited number of tissues. Moreover, the VEGF-B186 isoform was up-regulated in mouse and human tumor cell lines and primary tumors compared with their corresponding normal tissues. Taken together, our data suggest a fine genetic control of the expression of the two isoforms of VEGF-B, implying tissue- and cell-specific roles of the two VEGF-B isoforms.

Amino Acid Sequence↗
PubMed2001

An outbreak of serogroup C meningococcal disease associated with a secondary school.

An outbreak of 3 cases of invasive meningococcal disease occurred in a secondary school on 2 campuses in Victoria. Despite having only one isolate (a C.2a:nst strain), meningococcal DNA was identified by polymerase chain reaction (PCR) in early culture-negative blood specimens of the other 2 cases. Both were subsequently shown by PCR to be capsule serogroup C by PCR. An committee was formed to manage the response to the outbreak. Chemoprophylaxis was offered to family and children who had been in close contact with the cases. As one strain had been confirmed as being of a vaccine-preventable group, vaccination was offered to the whole school community as well as the families of cases. The direct costs of the outbreak to public health, which would have been identical whatever the causative serogroup, was $8,178. Vaccine charges accounted for most of the additional $56,941 cost of vaccinating the target group of 1600 students, staff, and families. No further cases have been associated with this outbreak.

Child↗
PubMed2001

Efficacy and safety of intravenous phytonadione (vitamin K1) in patients on long-term oral anticoagulant therapy.

OBJECTIVES: To determine the safety and efficacy of intravenously administered phytonadione (vitamin K1) in patients on routine oral warfarin anticoagulation. PATIENTS AND METHODS: This retrospective cohort study comprised adults who were taking warfarin, were not bleeding, and received intravenous phytonadione anticoagulation therapy before a diagnostic or therapeutic procedure between September 1, 1994, and March 31, 1996. The main outcome measures were adverse reactions to intravenously administered phytonadione, prothrombin-international normalized ratio time values, the incidence of bleeding and thrombosis after the procedure, and the time between the procedure and return to anticoagulation after resumption of warfarin treatment. RESULTS: Two (1.9%) of the 105 patients studied had suspected adverse reactions to intravenous phytonadione (dyspnea and chest tightness during infusion in both). For the 82 patients who underwent a procedure, the median time from phytonadione to procedure onset was 27 hours (range, 0.7-147 hours), which was significantly less for patients receiving an initial phytonadione dose of more than 1 mg (P=.009). None had thromboembolism after surgery, although 2 (2.4%) of the 82 patients had procedure-associated major bleeding. For the 60 patients resuming warfarin therapy after a procedure, the median time to return to therapeutic anticoagulation was 4.1 days (range, 0.8-31.7 days) and was unaffected by the phytonadione dosage. CONCLUSIONS: Intravenous phytonadione appears to be safe and is effective for semiurgent correction of long-term oral anticoagulation therapy before surgery. In small doses, it does not prolong the patient's time to return to therapeutic anticoagulation.

Administration, Oral↗
PubMed2001

Genotype and severity of long QT syndrome.

OBJECTIVES: To describe the state of the art of our understanding of the long QT syndromes and to provide the genetic correlation of clinical severity of patients with this disorder. DATE SOURCES: In this review, we outline data that were obtained from work in our laboratory, as well as information reported in the literature. STUDY SELECTION: The information in this review spans the last decade; data were obtained from the studies that had the most impact, as well as from recent work at our laboratory. DATA EXTRACTION: The data reported herein were extracted from the world literature on sudden death and the clinical aspects of long QT syndrome. The genes identified to date, mutations in these genes, and the biophysical perturbations in the mutated ion channels, as well as the severity of disease, are detailed. DATA SYNTHESIS: The extracted data are described as a state-of-the-art review. CONCLUSIONS: The long QT syndromes, genetically heterogeneous disorders due to mutations in genes encoding ion channels, are relatively common causes of syncope and sudden death. The affected genes, along with the genetic background of individuals, determine the clinical severity of disease. An understanding of the mechanisms responsible for long QT syndrome is expected to enable development of specific therapies.

Cation Transport Proteins↗
PubMed2001

The transport of a reversible proton pump antagonist, 5, 6-dimethyl-2-(4-Fluorophenylamino)-4-(1-methyl-1,2,3, 4-tetrahydroisoquinoline-2-yl) pyrimidine hydrochloride (YH1885), across caco-2 cell monolayers.

5,6-Dimethyl-2-(4-fluorophenylamino)-4-(1-methyl-1,2,3, 4-tetrahydroisoquinoline-2-yl) pyrimidine hydrochloride (YH1885) is under development as a novel acid pump antagonist by Yuhan Research Center. Previous studies have suggested that the AUC and C(max) of orally dosed YH1885 are dose-dependent in the range of 2 to 500 mg/kg. The objective of the present study was to investigate the absorption mechanism of YH1885 using a human colon carcinoma cell line, Caco-2. The cells were grown to confluency on a permeable polycarbonate membrane insert to permit loading of YH1885 on either the apical or basolateral side of the cell monolayer. The flux across the monolayer from the apical to basolateral side was 3 to 5 times greater than that from the basolateral to apical side. The uptake of YH1885 into the Caco-2 cell monolayer was saturable and appeared to be mediated by a high-affinity transporter, with an apparent K(m) of 1.47+/-0.21 microM and a V(max) of 25.14+/-1.16 pmol/cm(2)/40 s. The apical to basolateral transport across the monolayer was Na(+)-independent, H(+)-sensitive, and energy-dependent. The transport was inhibited significantly by the presence of structural analogs of YH1885 (e.g., YH957, YH1070, and YH1041), some pyrimidine nucleobases (uracil and 5-methyluracil), and nucleobase transport inhibitors (e.g., papaverine, dipyridamole, and phloridzin). These results demonstrate that the apical to basolateral transport of YH1885 across the Caco-2 cell monolayer is partially mediated by a nucleobase transport system, which exhibits high-affinity and energy-dependent properties for YH1885. Saturation of this transport system, in addition to the limited solubility of YH1885 (i.e., approximately 5.3 microM), appears to contribute to the dose-dependent bioavailability of the drug.

Biological Transport↗
PubMed2001

Neurotrophins BDNF and NT-3 promote axonal re-entry into the distal host spinal cord through Schwann cell-seeded mini-channels.

To promote axonal regeneration in the injured adult spinal cord, a two-phase repair strategy was employed to (i) bridge a spinal cord hemilesion cavity with a grafted Schwann cell (SC)-seeded mini-channel, and (ii) promote axonal re-entry into the distal cord by infusing two neurotrophins, BDNF and/or NT-3, directly into the distal cord parenchyma. Here we report that infusion of two neurotrophins, delivered alone or in combination, effectively promotes axonal outgrowth from SC-seeded mini-channels into the distal host spinal cord. When an anterogradely transported marker, PHA-L or BDA, was injected into the spinal cord 3 mm rostral to the graft, a large number of axons was observed to regenerate from the SC graft into the distal cord in neurotrophin-treated groups. A subpopulation of these axons was found to grow up to 6 mm within the distal spinal cord. These axons, which were confined mainly within the grey matter, arborized and formed structures which resemble terminal boutons. In channels containing no SCs, the infusion of neurotrophins did not promote axonal ingrowth from the proximal cord stump. In cases which received SC grafts but no neurotrophin infusion, axonal re-entry into the distal cord was limited. Thus, the present study demonstrates that regenerating axons not only cross a lesion site when a permissive cellular bridge is provided but also penetrate into the distal host spinal cord and elongate for a distance of several cord segments after the infusion of two neurotrophins. The latter event is prerequisite for establishment of appropriate connections between regenerating axons and target neurons and thus, functional recovery.

Animals↗
PubMed2001

[Cloning and primary expression analyses of down-regulated cDNA fragment in human gastric cancer].

OBJECTIVE: To identify human gastric cancer related genes. METHODS: Specimens of paired tumor, paratumor and normal gastric mucosa tissues were collected from five patients (male 3, female 2, with average age 48.8 +/- 18.1 years) who suffered from stomach antrum adenocarcinoma. Total RNA samples were extracted from these specimens, then studied by fluorescent differential display reverse transcription polymerase chain reaction (DDRT- PCR) analysis. The differentially expressed bands of interest were recovered, purified and cloned, then they were analyzed by sequencing, Northern blot and RT-PCR. Through BLAST, the sequencing results were compared with GenBank database for homology analysis. RESULTS: One of the interesting cDNA bands expressed much lower in all five tested tumor samples than in their normal and paratumor counterparts. This band was named W4. Northern blot analysis showed a consistent result with that of DDRT-PCR. W4 was cloned into pGEM-T easy vector. Sequence analysis showed that W4 consists of 712bp, this sequence was named W44. BLAST analysis revealed that W44 has extremely low sequence identity with any genes from GenBank and any sequences from EST database. This sequence data was submitted to GenBank with accession No. AF150631. RT-PCR analysis showed that W4 was expressed much lower in 11/15 gastric cancer tissue than in paratumor and normal samples. CONCLUSION: A novel cDNA sequence related to human stomach adenocarcinoma was identified.

Adult↗
PubMed2001

Genotype and severity of long QT syndrome.

Sudden cardiac death occurs in the United States with an incidence greater than 300,000 persons per year. The underlying cause of death is commonly considered to be due to primary or secondary arrhythmias. In cases in which no structural heart disease can be identified, the long QT syndromes (LQTS) are now commonly considered as likely causes. Multiple genes causing LQTS have been identified thus far, all encoding cardiac ion channels. These include two potassium channel alpha-subunits (KVLQT1, HERG), two potassium channel beta-subunits (minK, MiRP1), and one sodium channel gene (SCN5A). The purpose of this review is to describe the current understanding of the molecular genetics of LQTS and the resultant phenotypes.

Chromosome Mapping↗
PubMed2001

Thymidine kinase 1 immunoassay: a potential marker for breast cancer.

Previous research indicates that thymidine kinase I (TKI) possesses value as a tool for both prognosis and diagnosis in breast cancer. However, drawbacks to the existing radioassay for thymidine kinase have frustrated its clinical use. To overcome these drawbacks, we developed a monoclonal antibody to TK1. We have assessed this antibody for a linear antibody-antigen response and for reproducibility using ELISA techniques. We also have evaluated this antibody for TKI specificity as determined by Western blot. To test the accuracy of this monoclonal antibody further, we treated human MCF-7 breast cancer cells with tamoxifen and measured decreasing TKI activity and protein levels with the radioassay and with our monoclonal antibody in an ELISA, respectively. We then used the radioassay and our monoclonal antibody to measure TK1 activity and protein levels, respectively, in 218 serum samples of postoperative breast cancer patients and found a correlation between the two assays. Our results demonstrated that the TK1 immunoassay not only had a linear, reproducible, and specific response but accurately measured TK1 levels in both MCF-7 breast cancer cells and serum. Thus, our monoclonal antibody may demonstrate potential for practical use in a clinical setting for the management of breast cancer.

Antibodies, Monoclonal↗
PubMed2001

[Effect of PAI-1 antisense RNA on vascular endothelial growth factor expression in aorta smooth muscle cells cultured in vitro].

OBJECTIVE: To investigate the role of plasminogen activator inhibitor-1(PAI-1) antisense RNA in regulating the expression of PAI-1 and vascular endothelial growth factor (VEGF) in aorta smooth muscle cells cultured in vitro. METHODS: The second extron of PAI-1 was amplified with polymerase chain reaction(PCR), the production was inserted into eukaryotic cell expression vector pcDNA3.1 after it had been purified and cloned so as to construct PAI-1 antisense RNA recombination plasmid. The recombination plasmid was transfected into SMC. PAI-1 expression was detected by immunohistochemistry, Western blod and ELISA; the effects of PAI-1 variation on VEGF was examined by immunofluorescence. RESULTS: PAI-1 antigen was the lowest in cells on the third day after transfection; the expression of VEGF was also decreased. PAI-1 antigen gradually increased on the fifth day and VEGF increased correspondingly. On the seventh day, PAI-1 antigen and VEGF increased to nearly normal level. CONCLUSION: PAI-1 antisense RNA can block the translation progress of PAI-1 proteins effectively and inhibit the expression of VEGF in aorta smooth muscle cells.

Aorta↗
PubMed2001

Feasibility of a high-speed gamma-camera design using the high-yield-pileup-event-recovery method.

UNLABELLED: Higher count-rate gamma cameras than are currently used are needed if the technology is to fulfill its promise in positron coincidence imaging, radionuclide therapy dosimetry imaging, and cardiac first-pass imaging. The present single-crystal design coupled with conventional detector electronics and the traditional Anger-positioning algorithm hinder higher count-rate imaging because of the pileup of gamma-ray signals in the detector and electronics. At an interaction rate of 2 million events per second, the fraction of nonpileup events is < 20% of the total incident events. Hence, the recovery of pileup events can significantly increase the count-rate capability, increase the yield of imaging photons, and minimize image artifacts associated with pileups. A new technology to significantly enhance the performance of gamma cameras in this area is introduced. METHODS: We introduce a new electronic design called high-yield-pileup-event-recovery (HYPER) electronics for processing the detector signal in gamma cameras so that the individual gamma energies and positions of pileup events, including multiple pileups, can be resolved and recovered despite the mixing of signals. To illustrate the feasibility of the design concept, we have developed a small gamma-camera prototype with the HYPER-Anger electronics. The camera has a 10 x 10 x 1 cm NaI(Tl) crystal with four photomultipliers. Hot-spot and line sources with very high 99mTc activities were imaged. The phantoms were imaged continuously from 60,000 to 3,500,000 counts per second to illustrate the efficacy of the method as a function of counting rates. RESULTS: At 2-3 million events per second, all phantoms were imaged with little distortion, pileup, and dead-time loss. At these counting rates, multiple pileup events (> or = 3 events piling together) were the predominate occurrences, and the HYPER circuit functioned well to resolve and recover these events. The full width at half maximum of the line-spread function at 3,000,000 counts per second was 1.6 times that at 60,000 counts per second. CONCLUSION: This feasibility study showed that the HYPER electronic concept works; it can significantly increase the count-rate capability and dose efficiency of gamma cameras. In a larger clinical camera, multiple HYPER-Anger circuits may be implemented to further improve the imaging counting rates that we have shown by multiple times. This technology would facilitate the use of gamma cameras for radionuclide therapy dosimetry imaging, cardiac first-pass imaging, and positron coincidence imaging and the simultaneous acquisition of transmission and emission data using different isotopes with less cross-contamination between transmission and emission data.

Equipment Design↗
PubMed2001

[Malignant catarrhal fever in Switzerland. 1.Epidemiology].

Malignant catarrhal fever (MCF) is a usually fatal infectious disease of cattle with global distribution. Based on the recent introduction of a diagnostic PCR assay and a competitive inhibition ELISA (ciELISA) epidemiological data were collected on field cases in Switzerland. Throughout a three-year period, an MCF incidence of 0.6@1000 was observed, with a gradient of cases from Eastern to Western Switzerland. While the cantons Wallis, Vaud and Geneva reported no and the remaining western cantons only reported a few cases, the highest incidence was observed in the cantons Appenzell Innerrhoden, Lucern, Glarus, Grison, St. Gallen, Schwyz, and Thurgau. MCF occurred seasonally and an age-related clustering was also observed. About 50% of all cases and all outbreaks with more than one animal in a single herd occurred between April and June. Animals between six months and two years were strongly over represented. Observations on four surviving cattle showed that the outcome of the disease is not invariably fatal and that these persistently infected cows can produce healthy negative calves. Investigations on the aetiology indicate that the main reservoir for OvHV-2 is in sheep and possibly goats, while cattle do not normally harbor the virus. An OvHV-2 negative sheep herd was raised from lambs, which were reared colostrum-free and in isolation from their mothers. The success rate clearly indicated that vertical intrauterine infection is not the main mode of transmission among sheep. Therefore, horizontal, seasonally occurring transmission of OvHV-2 among sheep has to be assumed.

Age Factors↗
PubMed2001

Comparison of in vivo dopamine D2 receptor binding of [(123)I]AIBZM and [(123)I]IBZM in rat brain.

[(123)I]AIBZM, (S)-5-[(123)I]-Iodo-N-[(1-ethyl-2-pyrrolidinyl)]methyl-4-amine-2-methoxybenzamide is a derivative with high affinity for the D2 receptor. Labeling was achieved by the Iodogen method. The in vivo affinity for the D2 receptor and the biological characteristics were performed in rats. The brain uptake of [(123)I]AIBZM was significantly lower, however the striatum/cerebellum ratio (2h p.i.) was higher than that of [(123)I]IBZM. Because of the high affinity and its possibly lower unspecific binding compared to [(123)I]IBZM, [(123)I]AIBZM may be a potential imaging agent for the D2 dopamine receptor.

Animals↗