The Influencing Mechanism and Motivation of the Bystander on the Choice of Chinese Address Forms.

Chinese address terms exhibits a high degree of variability. Guided by the extended context of situation framework within the field of systemic functional linguistics, and taking the dialogues of the modern Chinese TV drama In the Name of People as examples, this study investigated how the bystander influences the choice of address terms. It is found that the appearance of the bystander influences the choice of address terms. Yet, it is not a direct process but is mediated by conversational atmosphere. Specifically, the presence of a bystander triggers "situational synergy" or changes interpersonal relationship, and then change the conversational atmosphere, both paths ultimately impact the choice of address terms. The underlying forces that lead to the variability of Chinese address terms are guan ben wèi and miàn zǐ. This study suggests the intricate impact of context on language choice, as well as the interdependency of context variables. In addition, by taking the concept of face beyond its European/North American milieu, and relocating it following the Chinese point of view, group orientation is valued, which contributes to face study.

Evaluation Mechanism of Political Discourse: A Holistic Approach.

Taking the economic issue of Trump's First State of the Union Address (SUA) as original data, the present study examined the evaluation features of political speeches by adopting a holistic approach, which includes both macro and micro dimensions. At the macro level, a series of semantic patterns were identified, with Goal-Achievement and General-Example Patterns being the most prevalent. They predetermine the evaluative tone, giving the surrounding statements evaluative meanings, exhibiting the radiating nature of evaluative meaning; at the micro level, a variety of resources have been identified, both explicit and implicit, lexical and syntactical, attitudinal and gradational, which collaborate to reinforce the subjective evaluation, revealing the holistic characteristic in the realization of evaluative meaning. Throughout the analysis, three evaluative mechanisms have been proposed, which are the coupling of meaning, semantic prosody, and tense switching. They collaborate and promote the subjective evaluation to be established and reinforced in a cumulative, gradient or hybrid pattern. In a narrow sense, the present study has partially revealed Trump's political discourse feature. Broadly speaking, it contributes to the theoretical development of the appraisal framework by refining existing evaluation systems through a holistic research paradigm, which in turn facilitates accurate interpretation of various types of discourse.

Association Between Admission Hyperglycemia and Outcomes After Endovascular Treatment in Acute Basilar Artery Occlusion.

INTRODUCTION: Admission hyperglycemia and high admission blood glucose levels have been associated with poor outcomes in acute ischemic stroke. However, the relationship between admission hyperglycemia and outcomes after endovascular treatment (EVT) in acute basilar artery occlusion (ABAO) still remain unclear. This study aimed to investigate the association between admission hyperglycemia and clinical outcomes in ABAO following EVT. METHODS: Patients from the BASILAR registry with admission blood glucose levels treated with EVT were included. We defined admission hyperglycemia as blood glucose levels ≥ 7.8 mmol/L. The primary outcome was favorable outcome [defined as a modified Rankin Scale score (mRS) of 0-3] at 90 days, Secondary outcomes included other functional outcomes (mRS 0-2, mRS 0-1) at 90 days, symptomatic intracerebral hemorrhage (sICH) within 48 h, and mortality at 90 days. RESULTS: Of 545 eligible patients included, the median age was 65 (IQR, 56-73) years, and median blood glucose level was 7.36 (IQR, 6.10-9.66) mmol/L. Multivariable logistic regression analysis showed that admission hyperglycemia was associated with decreased favorable outcome (mRS 0-3) (adjusted odds ratio = 0.52; 95% CI 0.35-0.79; P = 0.001), and increased mortality (adjusted odds ratio = 2.67; 95% CI 1.82-3.91; P < 0.001). Restricted cubic spline regression analysis showed that the blood glucose level had a non-linearity association with favorable outcome and mortality, and that there was no association between admission hyperglycemia and sICH. CONCLUSIONS: Our study suggest that admission hyperglycemia is associated with an increased risk of poor functional outcomes and mortality in patients with ABAO treated with EVT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), ChiCTR180001475.

Early blood pressure changes during systemic thrombolysis and its association with unexplained early neurological deterioration in small subcortical infarct.

Early neurological deterioration (END), observed in the acute phase of small subcortical infarct treated with intravenous thrombolysis (IVT), is not uncommon in these patients. However, in over half of the END cases, the exact cause is yet incompletely understood, which is so-called unexplained END (unEND). Our aim was to investigate the association of early blood pressure (BP) changes with unEND in patients with small subcortical infarct in the perforator territory of middle cerebral artery treated with IVT. Consecutive patients with acute small subcortical infarct treated with IVT were enrolled in this study. unEND was defined as≧2-point increase of NIHSS from baseline to 24 hours, without straightforward causes. BP excursions and BP variability were calculated and compared between patients with unNED and those without. A total of 168 patients with acute small subcortical infarct were included. Of them, there were 29 patients with unEND and 139 without END. During the first 24 hours following IVT, 66 (39.29%) patients had at least one BP excursion. Logistic regression analyses indicated that BP excursion presence (OR = 3.185, 95% CI: 1.238-8.198), SBP excursion presence (OR = 3.535, 95% CI: 1.366-9.143), and number of SBP excursion (OR = 1.466, 95% CI: 1.090-1.973) were independently associated with unEND. Although SBPSD (P < .001) and SBPCV (P < .001) were higher in patients with unEND than those without END, none of the parameters of BP variability predicted unEND in multivariate analyses. BP excursions above guideline thresholds during the first 24 hours following IVT for small subcortical infarct are common and are independently associated with unEND.

Optimisation of a Mouse Model of Cerebral Ischemia-Reperfusion to Address Issues of Survival and Model Reproducibility and Consistency.

Middle cerebral artery occlusion (MCAO) induced brain ischemia-reperfusion model in Mice is essential for understanding the pathology of stroke and investigating potential treatments, in which a variety of methods may be employed to block the middle cerebral artery (MCA), the most common being through the insertion of a monofilament; however, in vivo ischemia-reperfusion models are associated, particularly in mice, with high variability in lesion volume and high mortality. We aimed to optimise a mouse model of cerebral ischemia-reperfusion, addressing issues of mouse survival, model reproducibility, and consistency. The model was optimised in two ways: first, insert the monofilament directly through the internal carotid artery rather than through the external or common carotid artery, and second, by extending the length of the silicone coating on the monofilament, the length of the silicone coating enables embolization of the beginning of the middle cerebral artery, as well as the anterior cerebral artery and part of the posterior communicating artery. Results: We assessed various parameters, including blood flow changes in the middle cerebral artery, stability of the infarct area, correlation between infarct volume percentages and neurological deficit scores, mortality, weight changes, and wellbeing. We found that optimisation of the surgical procedure may improve mouse wellbeing and reduce mortality, through reduced weight loss and decrease the variability. In conclusion, we suggest that the optimisation of the model is superior for the study of both short and long-term outcomes of ischemic stroke. These results have considerable implications on stroke model selection for researchers.

Tat-SynGAP improves angiogenesis and post-stroke recovery by inhibiting MST1/JNK signaling.

Small G protein Ras induces the activation of apoptosis-related molecule mammalian Ste20-like kinase1 (MST1)/JNK signal pathway, which is involved in the regulation of tissue damage under pathological conditions such as ischemic stroke. Our previous study indicated that GTPase-activating protein for Ras (SynGAP), a negative regulator of Ras, could bind with postsynaptic density protein-93 (PSD-93) and Tat-SynGAP (670-685aa) small peptide to exhibit neuroprotective role. Here, we report that Tat-SynGAP (670-685aa) reduced cerebral edema at acute cerebral ischemia/reperfusion (I/R), improved integrity of blood-brain barrier, and decreased cortical and striatum neuronal injury. Mechanistically, Tat-SynGAP (670-685aa) not only inhibited the phosphorylation of MST1 and JNK and the cleavage of caspase-3, but also facilitated the expression of angiogenesis related molecules VEGF and Ang-1. In conclusion, Tat-SynGAP (670-685aa) reduces neuronal apoptosis and cerebral infarction volume and maintains vascular stability and blood-brain barrier integrity by inhibiting MST1/JNK signaling pathway.

Sex Differences of Acute Stroke Treatment and in Hospital Outcomes After Intravenous Thrombolysis in Patients With Ischemic Stroke.

Background: Many studies have suggested that the clinical features of male patients with ischemic stroke are different from those of female patients, but related data on Chinese patients are scarce. Therefore, this study aimed to identify the differences in treatment delays, complications related to intravenous thrombolysis, and prognosis between male and female patients with ischemic stroke in China. Methods: The data of patients with ischemic stroke who received intravenous thrombolysis were retrospectively analyzed. The data were obtained from the China Hospital Stroke Registry from January 2017 to April 2019. The general clinical characteristics, onset-to-door time, door-to-needle time, complications related to thrombolysis, National Institute of Health Stroke Scale (NIHSS) scores, and in-hospital mortality were compared between male and female patients to identify any sex differences in these factors. A multi-factorial analysis was conducted to explore whether sex is associated with in-hospital mortality and complications of intracerebral hemorrhage after thrombolysis. Results: A total of 26,475 patients with ischemic stroke who received intravenous thrombolysis were involved in the study. The data were collected from 902 hospitals in 29 provinces, autonomous regions, and municipalities in China. The door-to-needle time was longer in female than in male patients (49 [35, 67] vs. 48 [35, 65], P = 0.008). Furthermore, the frequencies of intracerebral hemorrhage (4.1 vs. 3.2%, P < 0.001) and in-hospital mortality (2.55 vs. 1.83%, P < 0.001) were higher in female vs. male patients. However, sex was not associated with intracerebral hemorrhage and in-hospital mortality according to the adjusted multi-factorial analysis. In addition, improvement in NIHSS scores was greater in female patients than in male patients [-3 (-6, -1) vs. -3 (-5, -1), P = 0.036]. Conclusions: After adjusting for other predictors sex was not associated with intracerebral hemorrhage after thrombolysis or in-hospital mortality. Further study is warranted to evaluate the long-term outcomes in the different sexes.

PSD-93 Interacts with SynGAP and Promotes SynGAP Ubiquitination and Ischemic Brain Injury in Mice.

Postsynaptic density protein-93 (PSD-93) plays an important role in ischemic brain injury through N-methyl-D-aspartate receptor (NMDAR)-triggered neurotoxicity. GTPase-activating protein for Ras (SynGAP) is a GAP specifically expressed in the central nervous system to regulate nerve development and synaptic plasticity. However, the link between PSD-93 and SynGAP and their role in ischemic brain injury remain elusive. Here, we showed that PSD-93 interacted with SynGAP and mediated SynGAP ubiquitination and degradation following ischemic brain injury. Proteasome inhibitor MG-132 could reverse the decrease of SynGAP protein level in wild-type mice following cerebral ischemia reperfusion through inhibiting SynGAP ubiquitination. Furthermore, NMDA receptor inhibitor MK801 could increase SynGAP protein level in wild-type mice following cerebral ischemia reperfusion. However, in PSD-93 knockout mice, MG-132 or NMDAR inhibitor had no significant effect on SynGAP expression. Both MG-132 and PSD-93 knockout reduced infarct volume and improved neurological deficit in mice at different time points after cerebral ischemia reperfusion. Furthermore, we identified that 670-685 amino acid sequence of SynGAP was essential to the binding of SynGAP to PSD-93, and designed a fusion peptide Tat-SynGAP (670-685aa) that could attenuate ischemic brain damage in wild-type mice. In conclusion, we provide the first evidence that PSD-93 directly interacts with SynGAP and mediates its ubiquitination and degradation to aggravate ischemic brain damage. Tat-SynGAP (670-685aa) may be considered as a candidate for treatment of acute ischemic stroke.

Mesenchymal Stem Cells Modified with Heme Oxygenase-1 Have Enhanced Paracrine Function and Attenuate Lipopolysaccharide-Induced Inflammatory and Oxidative Damage in Pulmonary Microvascular Endothelial Cells.

BACKGROUND/AIMS: Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has therapeutic effects on endothelial damage during acute lung injury (ALI). Heme oxygenase-1 (HO-1) can restore homeostasis and implement cytoprotective defense functions in many pathologic states. Therefore, we explored whether transduction of HO-1 into BM-MSCs (MSCs-HO-1) would have an increased beneficial effect on lipopolysaccharide (LPS)-induced inflammatory and oxidative damage in human pulmonary microvascular endothelial cells (PVECs). METHODS: MSCs were isolated from rat bone marrow and transfected with the HO-1 gene by a lentivirus vector. The phenotype and multilineage differentiation of MSCs were assessed. MSCs or MSCs-HO-1 were co-cultured with PVECs using a transwell system, and LPS was added to induce PVEC injury. The production of reactive oxygen species (ROS), and the activities of lipid peroxide (LPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in PVECs were determined by flow cytometry and colorimetric assays, respectively. The levels of human PVEC-derived tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-6 in the supernatants of the co-culture system, and the activity of nuclear transcription factor-κB and NF-E2-related factor 2 (Nrf2) in PVECs were examined by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of TNF-α, IL-1ß and IL-6 in PVECs was detected by quantitative real-time polymerase chain reaction (qRT-PCR), HO-1 expression and enzymatic activity in PVECs and the influence of zinc protoporphyrin (ZnPP) or HO-1 small interfering RNA on the above inflammatory and oxidative stress markers were evaluated. In addition, the expression of rat MSC-derived hepatocyte growth factor (HGF) and IL-10 was determined by ELISA and qRT-PCR. RESULTS: MSCs showed no significant changes in phenotype or multilineage differentiation after transduction. LPS strongly increased the production of inflammatory and oxidative stress indicators, as well as decreased the levels of antioxidant components and the activity of Nrf2 in PVECs. MSC co-cultivation ameliorated these detrimental effects in PVECs and MSCs-HO-1 further improved the damage to PVECs induced by LPS when compared with MSCs alone. The beneficial effects of MSCs-HO-1 were dependent on HO-1 overexpression and may be attributed to the enhanced paracrine production of HGF and IL-10. CONCLUSION: MSCs-HO-1 have an enhanced ability to improve LPS-induced inflammatory and oxidative damage in PVECs, and the mechanism may be partially associated with the enhanced paracrine function of the stem cells. These data encourage further testing of the beneficial effects of MSCs-HO-1 in ALI animal models.

[Meta-analysis of proximal gastrectomy and total gastrectomy for cancer of cardia and fundus].

OBJECTIVE: To assess the value of proximal gastrectomy (PG) and total gastrectomy (TG) for the treatment of cancer of cardia and fundus. METHODS: Publications on comparision between PG and TG in the treatment of cancer of cardia and fundus were collected, the data from the publications were matched with the PG group and the TG group respectively according to its corresponding surgical resection, and the data on postoperative complications, motality and 5-year survival rate were meta-analyzed by fixed effect model and random effect model. RESULTS: Thirteen reseaches on 2 219 patients were included in this study, 2 of which were randomly controlled studies. There were no significant differences in the postoperative complications (OR=1.00, 95%CI: 0.44-2.28,P>0.05) and mortality (OR=1.25, 95%CI: 0.62-2.48,P>0.05) between the PG group and the TG group, while there was significant difference in the 5-year survival rate (HR=0.87, 95%CI: 0.76-0.99,P=0.04). The 5-year survival rate in the TG group was higher than that in the PG group. CONCLUSION: Total gastrectomy for the treatment of cancer of cardia and fundus has better long-term therapetic effect.

Comparison of the replication and persistence of simian-human immunodeficiency viruses expressing Vif proteins with mutation of the SLQYLA or HCCH domains in macaques.

The Vif protein of primate lentiviruses interacts with APOBEC3 proteins, which results in shunting of the APOBEC3-Vif complex to the proteosome for degradation. Using the simian-human immunodeficiency virus (SHIV)/macaque model, we compared the replication and pathogenicity of SHIVs that express a Vif protein in which the entire SLQYLA (SHIV(Vif5A)) or HCCH (SHIV(VifHCCH(-))) domains were substituted with alanine residues. Each virus was inoculated into three macaques and various viral and immunological parameters followed for 6 months. All macaques maintained stable circulating CD4+ T cells, developed low viral loads, maintained the engineered mutations, yielded no histological lesions, and developed immunoprecipitating antibodies early post-inoculation. Sequence analysis of nef and vpu from three lymphoid tissues revealed a high percentage of G-to-A-substitutions. Our results show that while the presence of HCCH and SLQYLA domains are critical in vivo, there may exist APOBEC3 negative reservoirs that allow for low levels of viral replication and persistence but not disease.

[Maintenance chemotherapy in 43 patients with advanced non-small cell lung cancer: a retrospective study.].

BACKGROUND: It is unclear that patients with advanced non-small cell lung cancer (NSCLC) should receive prolonged chemotherapy or the best support, after achieving a maximum tumor response with 4 to 6 initial chemotherapy cycles. The aim of this study is to compare maintenance paclitaxel therapy with observation in advanced NSCLC patients. METHODS: A total of 166 patients with stage IIIB or IV NSCLC were treated with four monthly paclitaxel-carboplatin as following: paclitaxel 100 mg/m(2) weekly for 3 of 4 weeks with carboplatin (area under the curve[AUC]=6) on day 1. Patients who responded at week 16 were assigned to either weekly paclitaxel therapy(70 mg/m(2), 3 of 4 weeks) or observation. Maintenance therapy continued until disease progression, development of intercurrent illness, intolerable toxicity, or investigator decision to terminate treatment. RESULTS: There was a longer median time to progression in maintenance therapy compared with observation (P< 0.05). One- and two-year survival rates were 65% and 24% in the paclitaxel arm and 59% and 20% in the observation arm, respectively (P> 0.05). The performance status and the stage were the independent prognostic factors by Cox regression. CONCLUSIONS: Maintenance paclitaxel could benefit median time to progression but not survival time in patients who responded to induction chemotherapy. Nevertheless, further evaluation of maintenance therapy should be done before the concept is abandoned.

Protection of macaques against AIDS with a live attenuated SHIV vaccine is of finite duration.

Using background data that live vaccines against several viral pathogens are effective in inducing life-long protection against disease, we undertook studies in macaques to determine the duration of protection that two live SHIV vaccines could induce against AIDS. Earlier studies had established that macaques immunized once with a live vaccine and challenged 6 months later were protected, and that other macaques given two sequential inoculations of live vaccines were protected for at least 1 year. Protection was associated with persistence of the vaccine viruses. In this study, we sought to determine whether the duration of protection in macaques given a single inoculation of replication competent live vaccines would extend beyond 3 years. Two groups of four rhesus macaques were inoculated with two live SHIV vaccines, respectively. The viruses replicated transiently in all animals but at the 3-year time point, PCR analysis of PBMC did not detect DNA of either virus in any of the animals, and all were negative for CMI responses in the blood. All 8 animals succumbed to disease when challenged with pathogenic viruses.

Immunoprophylaxis against AIDS in macaques with a lentiviral DNA vaccine.

We earlier reported that immunization of macaques with a reverse transcriptase-deleted SHIV(KU2) (DeltartSHIV(KU2)) plasmid that contained HIV-1(HXB2) env and SIV gag-nef induced protection against AIDS caused by challenge virus SHIV89.6P with a heterologous env. We further deleted vif and integrase from DeltartSHIV(KU2) and substituted the 3'LTR with SV40 poly A sequences, creating Delta4SHIV(KU2) (M) and a parallel construct containing gag-nef of HIV-1(SF2), Delta4SHIV(KU2) (H). Six macaques received two intramuscular injections of the (M) DNA, and another six received three injections of the (H) DNA. Three of the latter group received two post-challenge boosts with (M) DNA vaccine. Seven virus control macaques were inoculated with SHIV89.6P. All twelve immunized macaques were challenged with SHIV89.6P virus, and CMI responses were measured by ELISPOT assays. Virus control animals all developed progressive infection, whereas vaccinated macaques from both groups controlled virus replication, with plasma viral loads dropping to undetectable levels between weeks 6 and 126 p.i. This DNA vaccine was efficacious even though it encoded Env, Gag, and Nef that were genetically distinct from the proteins in the challenge virus. The DNA vaccine induced broad-based protection without using viral proteins to boost the immunity.

Antigen expression kinetics and immune responses of mice immunized with noninfectious simian-human immunodeficiency virus DNA.

In a previous report we demonstrated that three injections of an rt-deleted noninfectious genome of the simian-human immunodeficiency virus SHIV(KU2) induced protection against AIDS in macaques (D. K. Singh, Z. Liu, D. Sheffer, G. A. Mackay, M. Smith, S. Dhillon, R. Hegde, F. Jia, I. Adany, and O. Narayan, J. Virol 79:3419-3428, 2005). To make this DNA safer, we deleted two more genes, the integrase gene and vif, along with the 3' long terminal repeat. We also replaced the gag, pro, and nef genes (SIVmac239 origin) with those of human immunodeficiency virus (HIV) type 1 strain SF2. The resultant construct, designated delta4SHIV(KU2) DNA, was used in this study to evaluate gene expression and immunogenicity in BALB/c mice. DNA-transfected human embryonic kidney epithelial cells (HEK 293) produced all of the major viral proteins and released p24 in the supernatant for 12 days. Inoculation of the vaccine DNA into the gastrocnemius muscles resulted in intense mononuclear cell infiltration at the inoculated sites and the production of viral p24 in myocytes, in infiltrating mononuclear cells, and in cells in the spleen and draining lymph nodes between 3 and 10 days postinoculation. Expression of p24 in the muscle cells peaked at day 7 and became undetectable after day 12. The same 12-day period of expression of p24 was observed in mice that were given a second injection 4 weeks after the first. Evaluation of immune responses in BALB/c mice revealed that the DNA induced enzyme-linked immunospot and antigen-specific proliferative cell-mediated immunity responses. The responses were stronger in mice that were coinjected with a second plasmid expressing granulocyte-macrophage colony-stimulating factor. Since new waves of viral antigen production could be induced with each boosting injection of the vaccine DNA, this DNA could be a safe and efficient agent to induce long-term protection against HIV.

A noninfectious simian/human immunodeficiency virus DNA vaccine that protects macaques against AIDS.

Simian/human immunodeficiency virus SHIV(KU2) replicates with extremely high titers in macaques. In order to determine whether the DNA of the viral genome could be used as a vaccine if the DNA were rendered noninfectious, we deleted the reverse transcriptase gene from SHIVKU2 and inserted this DNA (DeltartSHIVKU2) into a plasmid that was then used to test gene expression and immunogenicity. Transfection of Jurkat and human embryonic kidney epithelial (HEK 293) cells with the DNA resulted in production of all of the major viral proteins and their precursors and transient export of a large quantity of the Gag p27 into the supernatant fluid. As expected, no infectious virus was produced in these cultures. Four macaques were injected intradermally with 2 mg of the DNA at 0, 8, and 18 weeks. The animals developed neutralizing antibodies and low enzyme-linked immunospot assay (E-SPOT) titers against SHIVKU2. These four animals and two unvaccinated control animals were then challenged with heterologous SHIV89.6P administered into their rectums. The two control animals developed viral RNA titers exceeding 10(6) copies/ml of plasma, and these titers were accompanied by the loss of CD4+ T cells by 2 weeks after challenge. The two control animals died at weeks 8 and 16, respectively. All four of the immunized animals became infected with the challenge virus but developed lower titers of viral RNA in plasma than the control animals, and the titers decreased over time in three of the four macaques. The fourth animal remained viremic and died at week 47. Whereas the control animals failed to develop E-SPOT responses, all four of the immunized animals developed anamnestic E-SPOT responses after challenge. The animal that died developed the highest E-SPOT response and was the only one that produced neutralizing antibodies against the challenge virus. These results established that noninfectious DNA of pathogenic SHIV could be used as a vaccine to prevent AIDS, even though the immunological assays used did not predict the manner in which the challenge virus would replicate in the vaccinated animals.

Protection against late-onset AIDS in macaques prophylactically immunized with a live simian HIV vaccine was dependent on persistence of the vaccine virus.

This is a 5-year follow-up study on 12 macaques that were immunized orally with two live SHIV vaccines, six with V1 and six with V2. All 12 macaques became persistently infected after transient replication of the vaccine viruses; all were challenged vaginally 6 mo later with homologous pathogenic SHIV(KU-1). Two of the V1 group developed full-blown AIDS without evidence of vaccine virus DNA in tissues. The data on the 10 vaccinated survivors showed that all 10 became infected with SHIV(KU-1) and that DNA of both vaccine and SHIV(KU-1) viruses were present 6 mo postchallenge, with minimal replication of SHIV(KU-1). During the following 5 years, these animals remained persistently infected, but with only one of the two viruses. Six animals eliminated their vaccine virus after variable periods of time and four of these succumbed to reactivation of the challenge virus and AIDS. Five years after challenge, four latently infected animals, two with V2 and two with SHIV(KU-1), were reinoculated with SHIV(KU-1.) This resulted in transient superinfection and the animals promptly returned to their prechallenge status. Immunosuppression of the four animals 1 year later with Abs to CD8+ lymphocytes resulted in transiently productive replication of their respective latent viruses, and upon recovery of CD8+ lymphocytes, they reverted to their latent virus status. The major finding was that of eight animals that eliminated the vaccine virus, six developed AIDS. The two others harboring SHIV(KU-1) remain at risk for developing late-onset disease. The primary correlate against AIDS was persistence of the vaccine virus.

[Transformation characteristics of sulfur forms in acid sulfate soils under different soil water conditions].

Aimed to detect the quantitative impact of soil water condition on the transformation of sulfur forms in acid sulfate soils (ASS), a simulation test was made with 8 treatments. The results indicated that water was an important factor affecting the transformation processes. Wet but not inundated or over dried condition was benefit to the oxidation of pyrite S and the formation of water soluble S (WS-S) and exchangeable S (Ex-S) in ASS. In the three treatments with different inundated and drained off cycles, soil pyrite S content averagely decreased 1.29-3.20 g x kg(-1) during a single drained off period, while soil WS-S and Ex-S contents averagely increased 0.90-1.63 and 0.58-1.47 g x kg(-1), respectively. During inundated period, soil pyrite S content was relatively stable, but soil WS-S and Ex-S contents were decreased significantly due to the dilution of water. It was suggested that the total S (mainly WS-S) of ASS was discharged in drainage process, and the accumulative amount of the discharge and the transformation of the S forms were associated with the length of the inundated and drained off cycles. The dynamics of Jarosite S, organic S and element S in all treatments were also discussed here.

Microarray analysis of cytokine and chemokine genes in the brains of macaques with SHIV-encephalitis.

Human immunodeficiency virus (HIV)-encephalitis results from a cascade of viral-host interactions that lead to cytokine and chemokine imbalance, which then leads to neuropathologic manifestations of the disease. These include macrophage/microglia activation, astrocytosis and neuronal dysfunction or death. As the molecular mechanisms of this process are poorly understood, we used Atlas human cytokine or cytokine receptor microarray analysis to highlight gene expression profiles that accompanied encephalitis in Simian human immunodeficiency virus (SHIV) 89.6P-infected macaques. Of the 277 genes screened, marked upregulation of monocyte chemoattractant protein-1, interferon-inducible peptide IP-10 and interleukin-4 were observed specifically in the encephalitic brains. These genes are collectively known to promote macrophage infiltration and activation and virus replication. In contrast, genes regulating neurotrophic functions, such as brain-derived neurotrophic factor were downregulated. We also found that some of the apoptosis genes were up- or down-regulated. These data provide a comprehensive spectrum of gene expression that underscores the two major clinical manifestations of this unique syndrome: enhanced virus replication in brain macrophages and dystrophic changes in neurons.

Immunization of macaques with live simian human immunodeficiency virus (SHIV) vaccines conferred protection against AIDS induced by homologous and heterologous SHIVs and simian immunodeficiency virus.

To evaluate the vaccine potential of SHIVs attenuated by deletion of viral accessory genes, seven rhesus macaques were sequentially immunized with Delta vpu Delta nefSHIV-4 (vaccine-I) followed by Delta vpuSHIV(PPC) (vaccine-II). Despite the absence of virological evidence of productive infection with the vaccine strains, based on analysis of infectivity among peripheral blood mononuclear cells (PBMC) of the vaccinated animals, all seven animals developed binding as well as neutralizing antibodies against both vaccine-I and -II. The animals also developed vaccine virus-specific CTLs that recognized homologous as well as heterologous pathogenic SHIVs and SIV, and also soluble inhibitory factors that blocked the in vitro replication of the vaccine strains and different challenge viruses. Virus-specific cellular and humoral responses were sustained throughout a 58-week prechallenge period. To model aspects of natural transmission, the animals received a mucosal (rectal) challenge, with a mixture of three challenge viruses, SHIV(KU), SHIV(89.6)P, and SIV(mac)R71/17E. Two mock-vaccinated control animals inoculated with the same mixture of challenge viruses developed large numbers of infectious PBMC, high plasma viremia, and precipitous loss of CD4(+) T cells. The control animals did not develop any immune responses and succumbed to AIDS between 6 and 7 weeks postchallenge. All seven vaccinated animals became infected with challenge viruses as indicated by the presence of infectious cells in the PBMC and/or viral RNA in plasma. However, peak plasma viremia in vaccinates was two to nearly five logs lower than in the control animals and later plasma viral RNA became undetectable in all vaccinates. Vaccinated animals maintained normal CD4(+) T cell levels throughout the study. Challenge with pathogenic viruses caused massive anamnestic responses as determined by quantitation of virus-specific CD4(+) and CD8(+) T cells by intracellular IFN-gamma staining, and these cells persisted for at least 74 weeks. The study is still in progress and at this time DNA of SIV has become undetectable in lymph nodes of six of the seven vaccinates, SHIV(89.6)P in five of the seven, and SHIV(KU) in three of the seven animals.