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Biomedical subjects

Z Liu

Publications and source records attributed to Z Liu.

At least 955 records · Page 53Linked to original sources

Effectiveness of live-attenuated Japanese encephalitis vaccine (SA14-14-2): a case-control study.

BACKGROUND: Japanese encephalitis is a major cause of death and disability throughout Asia, including the Indian subcontinent. Although an effective vaccine for Japanese encephalitis is available, hundreds of millions of susceptible individuals remain unimmunised because of the vaccine's cost. In 1988, an inexpensive live-attenuated vaccine (SA14-14-2) was licensed in China. We have measured the effectiveness of this vaccine. METHODS: In a case-control study in rural Sichuan Province, China, the 56 cases consisted of children admitted to hospital with acute Japanese encephalitis, and were confirmed serologically. 1299 village-matched and age-matched controls were identified, and vaccination histories obtained from pre-existing written records. FINDINGS: The effectiveness of one dose was 80% (95% Cl 44 to 93%); that of two doses was 97.5% (86 to 99.6%). Controlling for multiple potential confounders did not alter these results. INTERPRETATION: We conclude that a regimen of two doses of live-attenuated Japanese encephalitis vaccine, administered 1 year apart, is effective in the prevention of clinically important disease. Subsequent study is needed to assure the safety of this vaccine.

Animals↗

Dynamic Ocean-Atmosphere Coupling: A Thermostat for the Tropics

The ocean currents connecting the western tropical Pacific Ocean with the eastern tropical Pacific Ocean are driven by surface winds. The surface winds are in turn driven by the sea-surface temperature (SST) differences between these two regions. This dynamic coupling between the atmosphere and ocean may limit the SST in the tropical Pacific Ocean to below 305 kelvin even in the absence of cloud feedbacks.

Journal Article↗

Electroconvulsive shock and lidocaine reveal rapid consolidation of spatial working memory in the water maze.

Head trauma leading to concussion and electroconvulsive shock (ECS) in humans causes amnesia for events that occurred shortly before the injury (retrograde amnesia). The present experiment investigated the amnesic effect of lidocaine and ECS in 25 rats trained on a working memory version of the Morris water task. Each day, the escape platform was moved to a new location; learning was evidenced by a decrease in the latency to find the platform from the first to the second trial. "Consolidation" of this newly encoded spatial engram was disrupted by bilateral inactivation of the dorsal hippocampus with 1 microliter of 4% lidocaine applied as soon as possible after the first trial. When trial 2 was given after recovery from the lidocaine (30 min after the injection), a normal decrease in latency indicated that the new engram was not disrupted. When trial 2 was given under the influence of lidocaine (5 min after injection), absence of latency decrease demonstrated both the success of the inactivation and the importance of hippocampus for the task. To examine the role of events immediately after learning, ECS (30 or 100 mA, 50 Hz, 1.2 sec) was applied 0 sec to 45 sec after a single escape to the new platform location. A 2-h delay between ECS and trial 2 allowed the effects of ECS to dissipate. ECS applied 45 sec or 30 sec after trial 1 caused no retrograde amnesia: escape latencies on trial 2 were the same as in control rats. However, ECS applied 0 sec or 15 sec after trial 1 induced clear retrograde amnesia: escape latencies on trial 2 were no shorter than on trial 1. It is concluded that the consolidation of a newly formed memory for spatial location can only be disrupted by ECS within 30 sec after learning.

Amnesia↗

Expanded CNS myelin sheaths formed in situ in the presence of an IgM antigalactocerebroside-producing hybridoma.

When O1 hybridoma cells, which produce an IgM antigalacto-cerebroside, are implanted into the dorsal columns of 4-8 d rat spinal cord, some of the myelin that subsequently develops in the immediate vicinity displays an abnormal periodicity. The spacings that are seen cluster at approximately 19 nm and 31 nm, roughly two and three times the normal 11 nm spacing. In the expanded sheaths, major dense lines are separated by broad extracellular spaces containing a dense material in which single or double rows of approximately 10 nm circular profiles can be identified, consistent with the "central rings" of IgM molecules. Because IgM is multivalent, it may serve to link adjacent lamellae together in place of intrinsic myelin molecules that normally interact at close range. Extensive direct contact between myelin components of successive myelin lamellae is thus not essential to signal the growth of the oligodendrocyte membrane or the spiral wrapping of that membrane around axons during myelinogenesis, or to stabilize the myelin spiral that forms.

Animals↗

Elevated relative fluorescence intensity of CD38 antigen expression on CD8+ T cells is a marker of poor prognosis in HIV infection: results of 6 years of follow-up.

Relative fluorescence intensity measurements from a flow cytometer were used to evaluate expression of CD38 and HLA-DR antigens. These molecules are associated with cellular activation and are present at increased levels on the CD8+ lymphocytes of HIV-infected subjects. In the current study, the prognostic value of mean fluorescence intensity measurements of CD38 and HLA-DR on CD8+ cells was compared to results from our previous study in which we reported prognostic value for an elevated percentage of CD8+ cells that were positive for expression of the CD38 antigen (Giorgi et al.: JAIDS 6:904-912, 1993). Using the proportional hazards model, elevated mean fluorescence intensity of CD38 expression on CD8+ cells had prognostic value for development of AIDS that was almost identical to the prognostic value of the percentage of CD8+ cells that were positive for expression of CD38. This prognostic value was in addition to that provided by the patient's CD4+ cell measurement. To our knowledge, this is the first report that a measurement of fluorescence intensity can be used as a prognostic marker in an immunodeficiency disease. Efforts are needed to establish methods that will allow widespread application of this observation in the clinical management of HIV-infected subjects.

ADP-ribosyl Cyclase↗

Characterization of a novel keratinocyte ubiquitin carrier protein.

A novel member of the ubiquitin carrier protein family, designated E2EPF, has been cloned by our laboratory and expressed in a bacterial system in an active form. Ubiquitin carrier proteins, or E2s, catalyze one step in a multistep process that leads to the covalent conjugation of ubiquitin to substrate proteins. In this paper, we show that recombinant E2EPF catalyzes auto/multiubiquitination, the conjugation of multiple ubiquitin molecules to itself. Multiubiquitination has been shown previously to be required for targeting of a substrate protein for rapid degradation. Using a rabbit reticulocyte lysate system, E2EPF was shown to support the degradation of a model substrate in an ATP- and ubiquitin-dependent fashion. In contrast to a previous study which showed that selective protein degradation in one system is dependent upon multiubiquitination via the lysine 48 residue of ubiquitin, multiubiquitination, and proteolytic targeting by E2EPF was shown here to be independent of the lysine 48 multiubiquitin linkage. This functional characterization of E2EPF revealed a combination of features that distinguishes this enzyme from all previously characterized members of the ubiquitin carrier protein family. These results also suggest several possible autoregulatory models for E2EPF involving auto- and multiubiquitination.

Adenosine Triphosphate↗

The role of immunosuppression in the long-term survival of tracheal allografts.

OBJECTIVES: To assess the functional aspects of vascularized tracheal allograft transplant models and the long-term fate of these allografts. To examine the effects of cyclosporin A (CsA), 10 mg/kg per day, on the long-term survival of vascularized tracheal allografts and the presence and significance of host immune tolerance after cessation of immunosuppression. DESIGN: In a rabbit model, tracheal allografts were orthotopically transplanted after an initial period of heterotopic fascia revascularization. A full-thickness skin allograft from the same donor was used as an external monitor of the rejection process. Treatment with CsA was discontinued (group 2) or given intermittently (group 3) after an initial course of continuous CsA administration varying from 2 to 10 weeks. The first group received a continuous regimen of CsA for 10 weeks. MAIN OUTCOME MEASURES: Tracheal and skin allograft deterioration, microcirculation of tracheal transplant, mucociliary clearance, and histopathologic examination. RESULTS: Tracheal allografts under continuous immunosuppression with CsA, 10 mg/kg per day, showed no rejection and remained functional with preservation of mucociliary activity. After an initial course of CsA to achieve solid tracheal union, subsequent cessation and intermittent pulsing of the immunosuppressant were insufficient in maintaining indefinite graft survival. Chronic allograft rejection with simultaneous endothelial graft repopulation could be induced by intermittent pulsing of CsA, which led to prolonged allograft survival in some group 3 animals. CONCLUSION: Continuous immunosuppression is necessary to preserve an optimal morphological and functional condition of tracheal allografts.

Animals↗

Development of a skin model based on insoluble fibrillar collagen.

A biocompatible, 3-dimensional, noncontracting, crosslinked collagen matrix was adapted to promote differentiation of epidermal keratinocytes. To produce the matrix, a 3% wt/wt dispersion of insoluble bovine collagen containing 5 mg polylysine/g collagen in 0.001 N HCl was blended, lyophilized, and crosslinked using a dehydrothermal technique. Matrices 4 cm2 and 3 mm thick were seeded with human dermal fibroblasts (1 x 10(5)/cm2). After 5 days in culture, the matrices were seeded with human epidermal keratinocytes (1 x 10(5)/cm2). The cultures were grown submerged for 1 week and raised to the liquid/air interface for 3 weeks to promote epidermal differentiation. Based on morphology and immunological staining with antibodies for human involucrin, keratin 1 (k1), filaggrin, and loricrin, the state of differentiation of the epidermal layer was nearly equivalent to that seen with cultures grown on contracted collagen lattices produced according to the methodology described in the literature and similar to the pattern produced in normal neonatal foreskin. These results demonstrate the usefulness of an in vitro skin model employing a crosslinked collagen matrix that permits the incorporation of additional covalently linked bioactive molecules during matrix formation.

Biocompatible Materials↗

Genes that regulate apoptosis in the mouse thymus.

Elimination of self-reactive T lymphocytes occurs during T-cell development in the thymus by a process known as negative selection. The mechanism that drives negative selection is apoptosis. To identify genes that regulate apoptosis in the mouse thymus, a library of negatively selected T cells was constructed and, by subtractive screening, several differentially regulated genes were isolated. Two transcripts that are repressed during cell death were identified, in addition to two induced transcripts. Further experiments demonstrated that cell death in thymocytes can occur via several induction pathways and each pathway appears to be regulated by a unique cascade of genes.

Animals↗

Effect of amino acids and alpha-amanitin on the development of rabbit embryos in modified protein-free KSOM with HEPES.

Four experiments were conducted to test the effects of Eagle's non-essential amino acids (NEAA) and essential amino acids (EAA), glycine, and the RNA polymerase inhibitor, alpha-amanitin, on the development of preimplantation rabbit embryos in modified protein-free KSOM medium. Embryos were distributed randomly into different treatments and cultured in 5% O2:5% CO2:90% N2. In experiment 1, 100% of the embryos became blastocysts in the medium with Eagle's 1X NEAA and 0.5X EAA, but 100% stopped development at the morula stage in KSOM without amino acids. These morulae failed to develop further when transferred to amino acid supplemented medium after 72 hr of culture. Glycine alone in modified KSOM (experiment 2) was ineffective in supporting development of 8-16-cell stage embryos past the morula stage. In experiment 3, the addition of 1X NEAA and 0.5X EAA at 0, 12, 24, 36, and 48 hr of culture resulted, respectively, in 57, 65, 65, 44, and 14% blastocysts on Day 3 (P < 0.05) and 86, 77, 77, 78, and 69% on Day 5 (P > 0.05). Omission of Eagle's amino acids until 48 hr clearly delayed embryo development. In experiment 4, when alpha-amanitin (20 microM) was added to the medium containing Eagle's amino acids after 0, 12, 24, 36, and 48 hr of culture most embryos cleaved only once or twice after adding the alpha-amanitin. Without the inhibitor, 94% of the zygotes developed into blastocysts. These results indicate that modified KSOM or KSOM plus glycine could not support rabbit embryo development past the morula stage, but this block was overcome by adding Eagle's amino acids. An exogenous source of amino acids was not critical for embryo development during the first 24 hr of culture, but was required after that for development to equal controls. Addition of alpha-amanitin at multiple pre-blastocyst stages limited further embryo development to one or two cleavage divisions, with no blastocyst development.

Amanitins↗

Indirect recognition of donor MHC Class II antigens in human transplantation.

To investigate the role of the indirect pathway of recognition in human allograft rejection, we have mapped the dominant T cell determinant of the HLA-DRbeta1*0101 molecule presented by the DRbeta1*1101 antigen. A synthetic peptide (pp 22-35) corresponding to the sequence of the dominant peptide determinant was used for testing the frequency of in vivo activated T cells in the graft and in the periphery. DRbeta1*1101-positive patients carrying a heart allograft mismatched for the HLA-DR1 antigen showed no reactivity to pp 22-35 during quiescence. However, interleukin-2-responsive T cells, which were pp 22-35 specific, were found in the circulation prior to and at the time of acute and chronic rejection. The response of in vivo and in vitro activated T cells was inhibited at high concentrations of peptide 22-35. This data suggests that indirect recognition plays an important role in allograft rejection and that it can be abolished by high zone tolerance induction.

Acute Disease↗

Evaluation of Bacillus thuringiensis and Bacillus sphaericus Strains from Chinese Soils Toxic to Mosquito Larvae

During our research to isolate and screen microbial agents, eight Bacillus thuringiensis isolates and five Bacillus sphaericus isolates were shown to have high toxicity to mosquito larvae. Comparing the LC50 values, four B. sphaericus isolates with LC50 values ranging from 0.50 to 1.47 ng/ml were about two to six times more toxic than strain 1593 (LC50 3.00 ng/ml) against larvae of Culex quinquefasciatus. Four B. thuringiensis isolates (LC50 values ranging from 3.80 to 7.54 ng/ml) and four B. sphaericus isolates with LC50 of 17.0 to 43.7 ng/ml were more toxic to Aedes aegypti than strain 1897 (LC50 8.46 ng/ml) and strain 1593 (LC50 67.3 ng/ml). As to Anopheles hyrcanus, the LC50 values of three B. sphaericus isolates ranging from 3.63 to 5.73 ng/ml were three to five times smaller than that of strain 1593 (LC50 16.1 ng/ml). Two B. sphaericus isolates showed high toxicity against mosquito larvae in the three genera Culex, Aedes, and Anopheles.

Journal Article↗

Sodium chloride, osmolyte, and osmolarity effects on blastocyst formation in bovine embryos produced by in vitro fertilization (IVF) and cultured in simple serum-free media.

PURPOSE: A simple serum-free medium (KSOM), relatively low in NaCl concentration, has been developed for culturing mouse zygotes produced in vivo. The present studies were designed to test modifications of this medium to establish optimal conditions for culture of bovine embryos produced in vitro. METHODS: Embryos were produced by standard in vitro fertilization procedures. They were cultured for 6 days in media varying in NaCl concentration and osmolarity with and without osmolytes, betaine or inositol. RESULTS: Increasing the NaCl concentration from 95 to 108.5 and 122 mM decreased blastocyst formation (P < 0.05). Partial substitution of NaCl by sorbitol indicated that both NaCl concentration and osmolarity were important. Neither betaine nor inositol protected the embryos against high concentrations of NaCl. CONCLUSIONS: The concentration of NaCl should not be higher than 95 mM and the total osmolarity of the medium should be between 250 and 270 mosmol.

Animals↗

Antenatal screening and fetal diagnosis of beta-thalassemia in a Chinese population: prevalence of the beta-thalassemia trait in the Guangzhou area of China.

In this paper beta-globin gene mutations were detected in 452 beta-thalassemia carriers from 13462 unselected individuals (6731 pregnant women and their husbands) who were screened for the beta-thalassemia trait in the Guangzhou area of China. The incidence of beta-thalassemia was calculated as 3.36%. This is higher than found in previous studies performed in southern China. Using reverse dot blot analysis, we found 11 types of mutations and identified the mutations in 446 (98.7%) of the 452 cases. Direct sequencing was carried out on the 6 unknown alleles, and a novel amber mutation in a beta 0-thalassemia gene (beta 37TGG --> TAG) was found in one of them. Thus, the prevalence and spectrum of beta-thalassemia mutations were obtained for this region. Twelve couples were detected at risk for thalassemia, and prenatal diagnosis was carried out in 11 of them. This is the largest number of Chinese subjects studied by DNA analysis to date and is the first report on the prospective diagnostic trial for beta-thalassemia in a Chinese population. In addition, we have performed 80 prenatal diagnoses based on screening for beta-thalassemia retrospectively.

Amino Acid Sequence↗

The influence of concordant xenografts on the humoral and cell-mediated immune responses to subsequent allografts in primates.

The humoral and cell-mediated immune responses to subsequent allografts were determined in primate recipients after concordant xenotransplantation as a bridge to allotransplantation. Heterotopic heart transplants (n = 4) were performed from cynomolgus monkeys into ABH type-matched olive baboons followed 2 weeks later by allotransplantation from ABH type-matched baboon donors. Allografts were explanted at 8 weeks. All recipients underwent splenectomy at the time of xenotransplantation and received immunosuppression with cyclosporine, azathioprine, and methylprednisolone. Concordant xenotransplantation in these primates did not induce humoral or cell-mediated immune responses that jeopardized subsequent allografts. The degree of xenospecific immune reactivity, as determined by specific cytotoxicity of recipient T-cell lines derived from the xenograft and extent of histologic xenograft rejection, did not predict the severity of subsequent allograft rejection. In two of the four recipients, xenotransplantation induced an alloreactive humoral response against antigens expressed by the B cells of more than 50% of members from a panel of 12 unrelated baboons. In all recipients, priming with xenogeneic splenocytes in vitro induced an accelerated proliferative T-cell response to allogeneic lymphocytes from 16% of this panel. This study affirms the role of concordant xenografts as appropriate biologic bridges to human allotransplantation. However, our results suggest that xenoreactive baboon memory CD4 T cells may recognize major histocompatibility complex class II--like structures shared between the xenogeneic and allogeneic targets. The potential allorecognition induced by a xenograft may affect the process of subsequent allograft donor selection.

Animals↗

Tetraploid or near-tetraploid clones characterized by two 8;21 translocations and other chromosomal abnormalities in two patients with acute myeloblastic leukemia.

Acute myeloblastic leukemia (AML) with tetraploidy is rare. There have been only six such cases studied with banding techniques in the literature. Two were diagnosed as having AML-M2 and found to have similar near-tetraploid karyotypes with t(8;21) and missing Y chromosomes. We report two further cases of AML with tetraploid or near-tetraploid clones characterized by two t(8;21) and other chromosomal changes. Their cytogenetic findings were compatible with the diagnosis of AML-M2. Giant and bizarre blasts were seen on bone marrow (BM) smears from both cases. Immunologically, the blasts express CD2, CD15, and HLA-DR in case 1 and CD2 and CD65 in case 2. Cytogenetic studies on BM cells at diagnosis revealed that both cases had three related abnormal clones besides a normal one: 46,XY,t(8;21) (2%)/46,idem,add(7)(q31)(6.8%)/92, idem x 2 (80.6%) for case 1; and 46,XX,t(8;21)(13.4%)/47, idem,+4 (46.3%)/94,idem x 2 (39.1%) for case 2. Flow cytometric analysis displayed two cell populations in the former: one was in the diploid range and the other was in the tetraploid range. The patients did not obtain complete remissions and survived four and six months, respectively. These results indicate that tetraploid or near-tetraploid clones are secondary events which are associated with t(8;21) leukemia and may be associated with poor prognostic significance.

Adult↗

Central effects of opioid agonists and naloxone on blood pressure and heart rate in normotensive and hypertensive rats.

1. The central cardiovascular effects of several opioid receptor selective agonists and the nonselective opioid antagonist, naloxone, were studied in anesthetized normotensive control rats, in spontaneously hypertensive rats (SHR), and in foot-shock-stressed rats. 2. Receptor-selective agonists injected into the rostral ventrolateral medulla (RVLM), paraventricular nucleus (PVN), and dorsal hippocampus (dHip) were DAGO (mu), DADLE (delta), and U50,488H (kappa). 3. DAGO and DADLE (3 nM) decreased arterial pressure and heart rate in RVLM and PVN of all rat strains, while U-50,488H (9 nM) had only minimal effects in these areas. 4. In dHip, only DADLE (3 nM) had depressor and bradycardic effects, and then, only in SHR, with DAGO and U50,488H being ineffective in any strain, even at 9 nM. 5. Prior injection of naloxone (10 nM) into the RVLM, PVN and dHip blocked and postinjection reversed the cardiovascular effects of the agonists. Naloxone alone increased blood pressure and heart rate in all three areas, in all rat strains except SHR, suggesting a tonic depressor effect of endogenous opioids. 6. Lack of significant quantitative differences in opioid agonist and antagonist effects between normotensive and hypertensive or stressed rats argues against a role for endogenous brain opioids in experimental hypertension.

Animals↗