[Progress in the study of communicable diseases in China, 1997].
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
K Luo
Publications and source records attributed to K Luo.
Signaling by chimeric erythropoietin-TGF-beta receptors: homodimerization of the cytoplasmic domain of the type I TGF-beta receptor and heterodimerization with the type II receptor are both required for intracellular signal transduction.
Transforming growth factor-beta (TGF-beta) affects multiple cellular functions through the type I and type II receptor Ser/Thr kinases (TbetaRI and TbetaRII). Analysis of TGF-beta signaling pathways has been hampered by the lack of cell lines in which both TbetaRI and TbetaRII are deleted, and by the inability to study signal transduction by TbetaRI independently of TbetaRII since TbetaRI does not bind TGF-beta directly. To overcome these problems, we constructed and expressed chimeric receptors with the extracellular domain of the erythropoietin receptor (EpoR) and the cytoplasmic domains of TbetaRI or TbetaRII. When expressed in Ba/F3 cells, which do not express EpoR, Epo induces the formation of a heteromeric complex between cell surface EpoR-TbetaRI and EpoR-TbetaRII chimeras. Neither the EpoR-TbetaRI nor the EpoR-TbetaRII chimera interacts with endogenous TGF-beta receptors. Ba/F3 cells expressing both EpoR-TbetaRI and EpoR-TbetaRII chimeras, but not EpoR-TbetaRI or EpoR-TbetaRII alone, undergo Epo-induced growth arrest. When expressed in Ba/F3 cells in the absence of the EpoR-TbetaRII chimera, EpoR-TbetaRI(T204D), a chimeric receptor with a point mutation in the GS domain of TbetaRI that is autophosphorylated constitutively, triggers growth inhibition in response to Epo. Thus, both homo- and heterodimerization of the cytoplasmic domain of the type I TGF-beta receptor are required for intracellular signal transduction leading to inhibition of cell proliferation. These chimeric receptors provide a unique system to study the function and signal transduction of individual TGF-beta receptor subunits independently of endogenous TGF-beta receptors.
Biopolymers↗
Perpendicular-electric-field dependence of exciton binding energy studied by continuous-wave photoluminescence.
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Journal Article↗
Whole genome analysis of hepatitis B virus from four cases of fulminant hepatitis: genetic variability and its potential role in disease pathogenicity.
The precore stop-codon variant of hepatitis B virus (HBV) has been associated with fulminant hepatitis but is also found in patients with persistent infection and chronic hepatitis. We have examined the possibility that the severe outcome of infection in patients with fulminant disease may be a result of additional genomic variation. We sequenced the entire HBV genome from three patients of Greek and one patient of Chinese origin with fulminant hepatitis, and from two patients with hepatitis B e antigen (HBeAg) positive chronic infection from the same regions, using direct sequencing of amplified viral DNA. Three of the fulminant cases were infected with the precore stop-codon variant HBeAg negative) and the fourth with the wild-type (HBeAg) positive virus. We compared sequences from our four fulminant isolates, and an additional fulminant isolate reported by others, with HBeAg positive carriers from the same regions and 12 published HBV genomes. There was a higher number of nucleotide and amino-acid substitutions throughout the HBV genome in the precore variant fulminant sequences than in the wild type. A cluster of mutations previously identified in the X region (126-132) in sequences reported in Japanese patients and encompassing the Enhancer II-Core Promoter region (1751-1768), were not found in our patients. We conclude that although there are no changes common to all sequences of HBV isolates from fulminant cases, some of these changes are in recognized cis-acting regulatory elements, whilst others are in the immediate vicinity of such elements. The effect of these mutations on viral genome transcription must now be determined.
Amino Acid Sequence↗
Hot spots of hepatitis B virus for genetic mutation in Chinese patients and its clinical significance.
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Hepatic Encephalopathy↗
[Identification of vertical transmission of hepatitis B virus from mother to children by direct sequencing a segment of surface gene of hepatitis B virus].
SUBJECTIVE: To explore the reason for the failure to interrupt vertical transmission of hepatitis B virus (HBV) from mother to children in Chinese subjects by vaccination. METHODS: HBV nucleotide sequences isolated from three sets of mother/children pairs were analyzed. HBV DNA from the surface antigen region encoding the amino acids 101 to 160 of hepatitis B surface antigen (HBsAg) was amplified and sequenced from HBsAg positive mother and their children. RESULTS: Nucleotide and deduced amino acid sequences were absolutely identical in the mother and children in family one and two respectively. However, there were five nucleotides different in family one's isolates compared with the family two's isolates. All of them were a subtype. In one child of family three, with coexisted HBsAg and anti-HBs, sequencing result revealed a point mutation which predicted a change from glycine to arginine at residue 145 in the second loop of the determinant. The mother and another child had a glycine at this position. CONCLUSION: This study revealed the vertical transmission linkage of HBV between the mother and children in a molecular level, and also first described a codon 145 immune escape mutant in Chinese vaccinated children.
Adult↗
[Fas expression and DNA impairment of hepatocyte in chronic hepatitis B].
To elucidate the role of apoptosis in the pathological lesion of hepatitis B virus (HBV) infection, biopsied liver tissue specimens of 38 patients with chronic hepatitis B of varying severity were investigated with in situ immunohistochemistry and TUNEL test. Apoptotic hepatocytes were found to be rare, while the nuclei of many cells were positively stained with TUNEL, suggesting 3'-OH ends generated as the DNA was impaired. Of the 17 cases with mild lesion or without piecemeal necrosis, 14 were negative or weakly positive with both Fas and TUNEL test. Of the 7 cases with piecemeal and bridging necrosis, none was strongly positive. In the 14 cases with active hepatitis and early cirrhosis, strongly positive results with Fas were found in 9 and with TUNEL in 3 respectively. It is suggested that the cytotoxic T lymphocyte (CTL)-Fas-apoptosis mechanism was involved in the hepatocyte death of hepatitis B as well. The Fas expression, DNA damage and apoptotic cells distributed mostly in the piecemeal necrosis region, and the ballooning and the necrotic hepatocytes were also clustering in this region. As both the apoptosis and necrosis are mediated by CTL, they are closely related: while transducted by different ways, they occurred independently.
Adult↗
The specificity of the transforming growth factor beta receptor kinases determined by a spatially addressable peptide library.
Type I and II receptors for the transforming growth factor beta (TGF-beta) are transmembrane serine/threonine kinases that are essential for TGF-beta signaling. However, little is known about their in vivo substrates or signal transduction pathways. To determine the substrate specificity of these kinases, we developed combinatorial peptide libraries synthesized on a hydrophilic matrix that is easily accessible to proteins in aqueous solutions. When we subjected these libraries to phosphorylation by the cAMP-dependent protein kinase, we obtained the optimal peptide sequence RRXS (I/L/V), in perfect agreement with the substrate sequence deduced from mutagenesis and crystal structure analyses. By using the same libraries, we showed that the optimal substrate peptide for both the type I and II TGF-beta receptors was KKKKKK(S/T)XXX. Since the two kinases are thought to play different roles in intracellular signal transduction, it was a surprise to find that they have almost identical substrate specificity. Our method is direct, sensitive, and simple and provides information about the kinase specificity for all the amino acid residues at each position.
Activin Receptors, Type I↗
A unique insertion in the S gene of surface antigen--negative hepatitis B virus Chinese carriers.
The presence of unique hepatitis B virus (HBV) variants has been investigated in two Chinese patients with chronic liver disease, whose sera were positive for HBV-DNA by dot blot hybridization or polymerase chain reaction (PCR) but hepatitis B surface antigen (HBsAg)-negative by conventional polyclonal antibody based immunoassays. PCR amplification of HBV-DNA followed by direct sequencing showed an insertion of six nucleotides, which introduced two additional amino acids between codons 122 and 123 in one patient (Isolate 1), whereas a nine nucleotide insertion in the other patient (Isolate 2) gave rise to three amino-acids between codons 123 and 124 immediately upstream from the 'a' determinant in the S gene. These insertions have not been described previously in any published sequences of the known subtypes and were absent from sequences of 30 HBsAg-positive Chinese patients from the same region. In the cases under study, the insertion is associated with four consecutive adenine molecules from nucleotides 516 to 519. It seems likely that this area is a hot spot for insertions in HBV. We found none of the previously described amino-acid deletions or substitutions in the pre-S1, pre-S2 and S genes, which are involved in unusual antigenic profiles. This finding suggests that genetic mutations in the S gene outside the 'a' determinant may be responsible for failure to detect HBsAg in some Chinese patients with chronic hepatitis caused by HBV infection.
Adult↗
The role of initial AIDS-defining illness in survival following AIDS.
OBJECTIVE: To examine the role of initial AIDS-defining illness in survival following AIDS and survival trends over time. DESIGN: States and Territory Health Departments notified new diagnoses of AIDS to the National AIDS Registry. Information on vital status and date of last medical contact was sought annually. METHODS: Survival was calculated for all adult and adolescent AIDS cases (n = 3204) in Australia diagnosed until 1 November 1991 and reported to the National AIDS Registry by 31 March 1994. The Cox regression method was used to identify independent predictors for survival. RESULTS: Age < 50 years, a CD4+ cell count > or = 100 x 10(6)/l and an initial diagnosis of Kaposi's sarcoma were independently associated with longer survival (P < 0.05). Acquisition of HIV through blood transfusion and the AIDS-defining illness non-Hodgkin's lymphoma were significantly associated with shorter survival. Survival improved substantially from 1986 to 1987, but did not improve further thereafter. A further study of initial AIDS-defining illnesses in a subgroup of individuals, i.e., men aged < 50 years at diagnosis who acquired HIV infection through homosexual or bisexual contact and diagnosed after 1987, showed that Kaposi's sarcoma, Pneumocystis carinii pneumonia, oesophageal candidiasis and herpes simplex virus as initial AIDS-defining illnesses had a relatively better prognosis than other single illnesses. Furthermore, patients with multiple illnesses did not have a worse prognosis than patients with a single illness, provided all illnesses were those with a better prognosis. CONCLUSIONS: Initial AIDS-defining illness, as well as age at diagnosis, year of diagnosis, HIV exposure and CD4+ cell count at diagnosis, plays an important role in survival following AIDS in Australia.
AIDS Dementia Complex↗
Development of Bacillus thuringiensis CryIC Resistance by Spodoptera exigua (Hubner) (Lepidoptera: Noctuidae).
Selection of resistance in Spodoptera exigua (Hubner) to an HD-1 spore-crystal mixture, CryIC (HD-133) inclusion bodies, and trypsinized toxin from Bacillus thuringiensis subsp. aizawai and B. thuringiensis subsp. entomocidus was attempted by using laboratory bioassays. No resistance to the HD-1 spore-crystal mixture could be achieved after 20 generations of selection. Significant levels of resistance (11-fold) to CryIC inclusion bodies expressed in Escherichia coli were observed after seven generations. Subsequent selection of the CryIC-resistant population with trypsinized CryIC toxin resulted, after 21 generations of CryIC selection, in a population of S. exigua that exhibited only 8% mortality at the highest toxin concentration tested (320 (mu)g/g), whereas the 50% lethal concentration was 4.30 (mu)g/g for the susceptible colony. Insects resistant to CryIC toxin from HD-133 also were resistant to trypsinized CryIA(b), CryIC from B. thuringiensis subsp. entomocidus, CryIE-CryIC fusion protein (G27), CryIH, and CryIIA. In vitro binding experiments with brush border membrane vesicles showed a twofold decrease in maximum CryIC binding, a fivefold difference in K(infd), and no difference in the concentration of binding sites for the CryIC-resistant insects compared with those for the susceptible insects. Resistance to CryIC was significantly reduced by the addition of HD-1 spores. Resistance to the CryIC toxin was still observed 12 generations after CryIC selection was removed. These results suggest that, in S. exigua, resistance to a single protein is more likely to occur than resistance to spore-crystal mixtures and that once resistance occurs, insects will be resistant to many other Cry proteins. These results have important implications for devising S. exigua resistance management strategies in the field.
Journal Article↗
[Gene mutation of hepatitis B virus].
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Genes, Viral↗
[Genetic variation in the cleavage site of the precore region of hepatitis B virus in Chinese patients with fulminant hepatitis].
In this study, a previously not documented variant of hepatitis B virus was described in Chinese patients with fulminant hepatitis. The entire precore/core region amplified from samples was cloned into a bacterial vector and sequenced by dideoxy chain termination reaction. Double amino acid substitutions were seen in the precore region in the isolates: one from glycine to aspartic acid at codon 29 previously reported; the other substitution of phenylalanine for valine at codon 17 in the cleavage site of hepatitis B virus. Loss of hepatitis B virus e antigen in these patients with fulminant hepatitis might therefore be due to the mutation in the cleavage site, rather than the emergence of a stop codon in the precore region of hepatitis B virus. Accumulation of hepatitis B e antigen precursor within the hepatocytes might account for the fulminant hepatitis exacerbation.
Amino Acid Sequence↗
HIV infection in recipients of blood products from donors with known duration of infection.
From a registry of people with transfusion-acquired HIV infection, 25 recipients were identified for whom the dates of HIV infection in the 8 corresponding donors could be established. Longer times to AIDS and to death in recipients were independently associated (p < 0.01) with the receipt of blood from donors who developed AIDS more than 10 years after HIV infection, as well as with older age and fewer transfusions. Sex, zidovudine treatment, and severity of illness at transfusion were not significantly associated with survival.
Acquired Immunodeficiency Syndrome↗
Reversal of resistance to Bacillus thuringiensis in Plutella xylostella.
Continued success of the most widely used biopesticide, Bacillus thuringiensis, is threatened by development of resistance in pests. Experiments with Plutella xylostella (diamondback moth), the first insect with field populations resistant to B. thuringiensis, revealed factors that promote reversal of resistance. In strains of P. xylostella with 25- to 2800-fold resistance to B. thuringiensis compared with unselected strains, reversal of resistance occurred when exposure to B. thuringiensis was stopped for many generations. Reversal of resistance was associated with restoration of binding of B. thuringiensis toxin CryIA(c) to brush-border membrane vesicles and with increased biotic fitness. Compared with susceptible colonies, revertant colonies had a higher proportion of extremely resistant individuals. Revertant colonies responded rapidly to reselection for resistance. Understanding reversal of resistance will help to design strategies for extending the usefulness of this environmentally benign insecticide.
Animals↗
Effect of dimethylsulfoxide and hydroxyethyl starch in the preservation of fractionated human marrow cells.
Fractionated human bone marrow cells, isolated by density centrifugation, could be well cryopreserved in both a DMSO/HES/albumin mixture and the conventional cryoprotectant (DMSO/serum) with either a programmed freezer or a -80 degrees C freezer. A lower initial temperature rise and a delayed plateau phase in the mixture in comparison with those in the DMSO/serum were observed using a programmed procedure without heat fusion compensation. Plateau phase in the mixture could also be shortened with increased liquid nitrogen to minimize the transition phase duration. However, the method of mononuclear cells immersed in a -80 degrees C freezer and stored in liquid nitrogen is simple and easily standardized. Additionally, widely used lactated Ringer's solution instead of Normosol-R can be employed to prepare the mixture for the preservation of fractionated cells.
Albumins↗
Removal of Adsorbed Toxin Fragments That Modify Bacillus thuringiensis CryIC delta-Endotoxin Iodination and Binding by Sodium Dodecyl Sulfate Treatment and Renaturation.
We report that 10- and 25-kDa toxin fragments adhere to CryIC prepared from Bacillus thuringiensis insecticidal crystals, block iodination, and alter membrane binding. There is no apparent affect on CryIC toxicity against Spodoptera exigua. Associated peptides remained bound to CryIC in the presence of 50 mM dithiothreitol or 6 M urea. A novel detergent-renaturation procedure was developed for the purification of B. thuringiensis CryIC toxin. Sodium dodecyl sulfate (SDS) treatment followed by gel filtration chromatography yielded a homogeneous 62-kDa CryIC toxin. After removal of SDS and renaturation, the purified CryIC toxin was fully insecticidal to S. exigua larvae. I-labeled CryIC bound with high affinity to brush border membrane vesicles from S. exigua larvae.
Journal Article↗
Enterprise-based sheltered workshops in Nanjing. A new model for the community rehabilitation of mentally ill workers.
This paper describes the development of community mental health services in Nanjing and reports on a retrospective study that compared the two-year outcome for 78 schizophrenic patients who attended four enterprise-based sheltered workshops (experimental group) with that of 78 schizophrenic patients who attended an out-patient clinic (control group). Despite having a longer course of illness and more prior hospital admissions than patients in the control group, at the end of the two years patients treated in enterprise-based sheltered workshops had significantly less psychosocial dysfunction (mean Social Dysfunction Screening Schedule score 3.4 (s.d. 0.2) v. 7.4 (s.d. 0.7), t = 49.2, d.f. 154, P < 0.001) and less severe psychiatric symptomatology (mean Brief Psychiatric Rating Scale score 33.1 (s.d. 2.7) v. 54.1 (s.d. 2.9), t = 47.0, d.f. 154, P < 0.001). Moreover, compared with the control group, over the two year period a smaller proportion of the experimental group experienced a clinical relapse (14.1% v. 38.5%, chi 2 = 5.10, d.f. 1, P < 0.05) or hospital readmission (7.7% v. 21.8%, chi 2 = 10.7, d.f. 1, P < 0.01). We conclude that the organisation of on-site sheltered workshops for mentally ill factory workers is an effective model for promoting community mental health that merits widespread application in China.
Adult↗