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Biomedical subjects

H Gu

Publications and source records attributed to H Gu.

At least 73 records · Page 4Linked to original sources

[A case-control study on the risk factors of epidemic hemorrhagic fever].

OBJECTIVE: To study the risk factors of epidemic hemorrhagic fever (EHF). METHODS: A 1:1 matched case-control study was conducted to analyse EHF risk factors. RESULTS: One hundred and eighty-five matched pairs were investigated. Five factors were associated with risks of the disease, including rodent activity in house, farm working, travel, annual average income of an individual and ground material of the house, when chi(2) test and logistic regression model were processed respectively. The coefficients of rodent activity in house, farm working, travel, annual average income of an individual and ground material of the house in multivariable Logistic regression model were 1.377, 1.687, 1.630, -1.216 and -0.888, respectively, when P value < 0.05 was observed. CONCLUSIONS: Factors as high average income of individuals, brick or cement used as material of the ground in the house, seemed to be protective factors of EHF, which were important to the control and prevention of EHF.

Adult↗

[Safety and immunogenicity of inactivated bivalent EHF vaccine in humans].

OBJECTIVE: Safety and immunogenicity of inactivated bivalent EHF vaccine in humans were evaluated in the epidemic area of Zhejiang province, China. METHODS: Susceptible persons with negative anti-EHF were selected in Jiande county, Zhejiang province to receive 3 doses of inactivated bivalent EHF vaccine at 0, 7, 28 days. A booster injection was given one year after the primary immunization. Antibody responses were measured in human volunteers by IFA and MCPENT. Local and general reactions were recorded within 72 hours after each vaccination by physicians. RESULTS: Two weeks after the primary vaccination, 99.04% of the subjects developed significant hantavirus antibody titre measured by IFA which had a 37.34% drop one year after the primary vaccination. Seroconversion rate increased to 100% two weeks after the booster dose. Neutralising antibody titres paralleled this trend with 100% of vaccine recipients producing neutralising antibody two weeks after the primary doses. However, it dropped to 80% one year after the primary vaccination. One hundred percent of the vaccine recipients started to respond two weeks after boosting. The geometric mean titre (GMT) of neutralising antibody against 76 - 118 and UR were 18.27 +/- 2.21 and 12.47 +/- 2.16 respectively after the primary injections, but it increased to 37.09 +/- 2.24 and 32.61 +/- 2.05 respectively after the secondary immunization. General and local reaction rates were 0.46% and 1.98%, with no severe side effects observed in the vaccinees. CONCLUSION: The vaccine was well tolerated and could induce good humoral immune response.

Antibodies, Viral↗

[Effect of intravascular low level laser irradiation used in avulsion injury].

OBJECTIVE: To explore the effect of intravascular low level He-Ne laser irradiation on skin flap survival after orthotopic transplantation in avulsion injury. METHODS: Fifty eight cases suffered avulsion injury were treated by debridement and orthotopic transplantation of avulsed flap within 6 hours, 31 of them were received intravascular low level He-Ne laser irradiation and routine treatment, and 27 of them were received routine treatment as control group. RESULTS: The survival area and quality of avulsed flap in the experimental group were superior to that of control group after 15 days of operation, and the hemorheological items were markedly changed at 5 days after operation. CONCLUSION: The better flap survival after orthotopic transplantation in avulsion injury can be improved by intravascular low level He-Ne laser irradiation through changed superoxide dismutase activity and hemorheological items in optimal irradiation intensity.

Accidents, Traffic↗

The role of external loop regions in serotonin transport. Loop scanning mutagenesis of the serotonin transporter external domain.

Chimeric transporters were constructed in which the predicted external loops of the serotonin transporter (SERT) were replaced one at a time with a corresponding sequence from the norepinephrine transporter (NET). All of the chimeric transporters were expressed at levels equal to or greater than those of wild type SERT, but the transport and binding activity of the mutants varied greatly. In particular, mutants in which the NET sequence replaced external loops 4 or 6 of SERT had transport activity 5% or less than that of wild type, and the loop 5 replacement was essentially inactive. In some of these mutants, binding of a high affinity cocaine analog was less affected than transport, suggesting that the mutation had less effect on the initial binding steps in transport than on subsequent conformational changes. The more severely affected mutants also displayed an altered response to Na(+). In contrast to the dramatic reduction in transport and binding, the specificity of ligand binding was essentially unchanged. Chimeric transporters did not gain affinity for dopamine, a NET substrate, or desipramine, an inhibitor, at the expense of affinity for serotonin or paroxetine, a selective SERT inhibitor. The results suggest that external loops are not the primary determinants of substrate and inhibitor binding sites. However, they are not merely passive structures connecting transmembrane segments but rather active elements responsible for maintaining the stability and conformational flexibility of the transporter.

Base Sequence↗

The poly(A)-limiting element is a conserved cis-acting sequence that regulates poly(A) tail length on nuclear pre-mRNAs.

Most vertebrate mRNAs exit the nucleus with a 200+-residue poly(A) tail and are deadenylated to yield heterogeneous polymers of 50-200 adenosine residues on any given mRNA. We previously reported that Xenopus albumin mRNA and pre-mRNA have an unusually short, discrete 17-residue poly(A) tail and showed that regulation of poly(A) length is controlled independently by two cis-acting poly(A)-limiting elements (PLE A and PLE B) located in the terminal exon. The present study sought to determine the generality of this regulatory mechanism. Transferrin mRNA also has a discrete <20-nt poly(A) tail, and deletion mapping experiments identified an element homologous to the albumin gene PLE B within the terminal exon of the transferrin gene that conferred poly(A) length regulation on a globin reporter mRNA. Based on this similarity the PLE B sequence was used in a database search to identify candidate mRNA targets for regulated polyadenylation. Of the several hundred sequences identified in this manner we focused on HIV-EP2/Schnurri-2, a member of a family of genes encoding related zinc finger transcription factors. A striking feature of the PLE-like element in these genes is its location 10-33 bp upstream of the translation stop codon. We demonstrate that HIV-EP2 mRNA has a <20-nt poly(A) tail, for which the identified PLE-like sequence is responsible. These results indicate that the presence of a PLE can predict mRNAs with <20-nt poly(A) tails, and that nuclear regulation of poly(A) tail length is a feature of many mRNAs.

Animals↗

Frequency of the fragile X syndrome in Chinese mentally retarded populations is similar to that in Caucasians.

Fragile X syndrome is recognized as the most common inherited cause of mental retardation in western countries. The prevalence of the fragile X syndrome in Asian populations is uncertain. We report a multi-institutional collaborative study of molecular screening for the fragile X syndrome from 1,127 Chinese mentally retarded (MR) individuals. We found that 2.8% of the Chinese MR population screened by DNA analysis had the fragile X full mutation. Our screening indicated that the fragile X syndrome prevalence was very close to that of Caucasian subjects. In addition, we found that 62.5% of fragile X chromosomes had a single haplotype for DXS548-FRAXAC1 (21-18 repeats) which was present in only 9.7% of controls. This unique distribution of microsatellite markers flanking the FMR1 CGG repeats suggests that the fragile X syndrome in Chinese populations, as in the Caucasian, may also be derived from founder chromosomes.

Alleles↗

Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-beta.

SMAD3 is one of the intracellular mediators that transduces signals from transforming growth factor-beta (TGF-beta) and activin receptors. We show that SMAD3 mutant mice generated by gene targeting die between 1 and 8 months due to a primary defect in immune function. Symptomatic mice exhibit thymic involution, enlarged lymph nodes, and formation of bacterial abscesses adjacent to mucosal surfaces. Mutant T cells exhibit an activated phenotype in vivo, and are not inhibited by TGF-beta1 in vitro. Mutant neutrophils are also impaired in their chemotactic response toward TGF-beta. Chronic intestinal inflammation is infrequently associated with colonic adenocarcinoma in mice older than 6 months of age. These data suggest that SMAD3 has an important role in TGF-beta-mediated regulation of T cell activation and mucosal immunity, and that the loss of these functions is responsible for chronic infection and the lethality of Smad3-null mice.

Animals↗

The refolding, purification, and activity analysis of a rice Bowman-Birk inhibitor expressed in Escherichia coli.

A putative rice trypsin/chymotrypsin inhibitor of the Bowman-Birk family, RBBI-8 of about 20 kDa, was expressed in Escherichia coli as a fusion protein bearing an N-terminal (His)6 purification tag. The expressed recombinant protein, rRBBI-8, is insoluble and accumulates as inclusion bodies. The insoluble protein was solubilized in 8 M urea under reducing environment and then refolded into its active conformation under optimized redox conditions. Strategies used to optimize yield and efficiency include selecting the redox system, increasing protein concentration during refolding by adding the denatured protein in a stepwise way, utilizing additives to prevent aggregation, and selecting buffer-exchanging conditions. A Ni-chelate affinity column was then employed to purify the renatured protein. rRBBI-8 shows strong inhibitory activity against trypsin and it can slightly inhibit chymotrypsin. In this study, a refolding and purification system was set up for this cysteine-rich recombinant protein expressed in a prokaryotic system.

Amino Acid Sequence↗

Identification of highly methylated arginine residues in an endogenous 20-kDa polypeptide in cancer cells.

Enzymatic methylation of endogenous proteins in several cancer cell lines was investigated to understand a possible relationship between protein-arginine methylation and cellular proliferation. Cytosolic extracts prepared from several cancer cells (HeLa, HCT-48, A549, and HepG2) and incubated with S-adenosyl-L-[methyl-3H]methionine revealed an intensely [methyl-3H]-labeled 20-kDa polypeptide. On the other hand, cytosolic extracts prepared from normal colon cells did not show any methylation of the 20-kDa protein under identical conditions. To identify nature of the 20-kDa polypeptide, purified histones were methylated with HCT-48 cytosolic extracts and analyzed by SDS-PAGE. However, none of the histones comigrated with the methylated 20-kDa polypeptide, indicating that it is unlikely to be any of the histone subclasses. The [methyl-3H]group in the 20-kDa polypeptide was stable at pH 10-11 (37 degrees C for 30 min) and methylation was not stimulated by GTPgammaS (4 mM), thus the reaction is neither carboxyl methylesterification on isoaspartyl residues, nor on C-terminal farnesylated cysteine. The present study together with the previous identification of N(G)-methylated arginine residues in the HCT-48 cytosol fraction suggests that this novel endogenous 20-kDa arginine-methylation is a cellular proliferation-related posttranslational modification reaction.

Animals↗

A methodology for partitioning a vocabulary hierarchy into trees.

Controlled medical vocabularies are useful in application areas such as medical information systems and decision-support systems. However, such vocabularies are large and complex, and working with them can be daunting. It is important to provide a means for orienting vocabulary designers and users to the vocabulary's contents. We describe a methodology for partitioning a vocabulary based on an IS-A hierarchy into small meaningful pieces. The methodology uses our disciplined modeling framework to refine the IS-A hierarchy according to prescribed rules in a process carried out by a user in conjunction with the computer. The partitioning of the hierarchy implies a partitioning of the vocabulary. We demonstrate the methodology with respect to a complex sample of the MED, an existing medical vocabulary.

Models, Theoretical↗

Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice.

In most mammals the pancreas develops from the foregut endoderm as ventral and dorsal buds. These buds fuse and develop into a complex organ composed of endocrine, exocrine and ductal components. This developmental process depends upon an integrated network of transcription factors. Gene targeting experiments have revealed critical roles for Pdx1, Isl1, Pax4, Pax6 and Nkx2-2 (refs 3,4,5,6,7, 8,9,10). The homeobox gene HLXB9 (encoding HB9) is prominently expressed in adult human pancreas, although its role in pancreas development and function is unknown. To facilitate its study, we isolated the mouse HLXB9 orthologue, Hlxb9. During mouse development, the dorsal and ventral pancreatic buds and mature beta-cells in the islets of Langerhans express Hlxb9. In mice homologous for a null mutation of Hlxb9, the dorsal lobe of the pancreas fails to develop. The remnant Hlxb9-/- pancreas has small islets of Langerhans with reduced numbers of insulin-producing beta-cells. Hlxb9-/- beta-cells express low levels of the glucose transporter Glut2 and homeodomain factor Nkx 6-1. Thus, Hlxb9 is key to normal pancreas development and function.

Animals↗

Robustness of protein folding kinetics to surface hydrophobic substitutions.

We use both combinatorial and site-directed mutagenesis to explore the consequences of surface hydrophobic substitutions for the folding of two small single domain proteins, the src SH3 domain, and the IgG binding domain of Peptostreptococcal protein L. We find that in almost every case, destabilizing surface hydrophobic substitutions have much larger effects on the rate of unfolding than on the rate of folding, suggesting that nonnative hydrophobic interactions do not significantly interfere with the rate of core assembly.

Amino Acid Substitution↗

Regulation of early events in integrin signaling by protein tyrosine phosphatase SHP-2.

The nontransmembrane protein tyrosine phosphatase SHP-2 plays a critical role in growth factor and cytokine signaling pathways. Previous studies revealed that a fraction of SHP-2 moves to focal contacts upon integrin engagement and that SHP-2 binds to SHP substrate 1 (SHPS-1)/SIRP-1alpha, a transmembrane glycoprotein with adhesion molecule characteristics (Y. Fujioka et al., Mol. Cell. Biol. 16:6887-6899, 1996; M. Tsuda et al., J. Biol. Chem. 273:13223-13229). Therefore, we asked whether SHP2-SHPS-1 complexes participate in integrin signaling. SHPS-1 tyrosyl phosphorylation increased upon plating of murine fibroblasts onto specific extracellular matrices. Both in vitro and in vivo studies indicate that SHPS-1 tyrosyl phosphorylation is catalyzed by Src family protein tyrosine kinases (PTKs). Overexpression of SHPS-1 in 293 cells potentiated integrin-induced mitogen-activated protein kinase (MAPK) activation, and potentiation required functional SHP-2. To further explore the role of SHP-2 in integrin signaling, we analyzed the responses of SHP-2 exon 3(-/-) and wild-type cell lines to being plated on fibronectin. Integrin-induced activation of Src family PTKs, tyrosyl phosphorylation of several focal adhesion proteins, MAPK activation, and the ability to spread on fibronectin were defective in SHP-2 mutant fibroblasts but were restored upon SHP-2 expression. Our data suggest a positive-feedback model in which, upon integrin engagement, basal levels of c-Src activity catalyze the tyrosyl phosphorylation of SHPS-1, thereby recruiting SHP-2 to the plasma membrane, where, perhaps by further activating Src PTKs, SHP-2 transduces positive signals for downstream events such as MAPK activation and cell shape changes.

Animals↗

Modeling the UMLS using an OODB.

The Unified Medical Language System combines many well established authoritative medical informatics terminologies in one system. Such a resource is very valuable to the healthcare industry. However, the UMLS is very large and complex and poses serious comprehension problems for users and maintenance personnel. Furthermore, the sets of concepts of semantic types are not semantically uniform and thus are difficult to study. We describe a method to represent two components of the UMLS, the Metathesaurus (META) and the Semantic Network, as an OODB. The resulting UMLS OODB schema is deeper and more refined than the Semantic Network. It offers semantically uniform classes, which improves support for comprehension and navigation of META. The UMLS OODB also exposes problems in the semantic type classifications.

Classification↗

[Apolipoportein E polymorphism, serum lipids and apolipoproteins of 362 Han national subjects in Chengdu area].

This investigation was conducted to observe the frequency distribution of apoE phenotypes and alleles and to explore the relationship between apoE polymorphism and plasma lipids or apolipoproteins in Chinese population. ApoE phenotypes were assayed by isoelectric focusing and immunoblotting with serum. Serum lipids and apoA I, B100, C II, C III, E were determined in a random subset of 362 subjects including 268 males and 94 females with a mean age of 43.7 +/- 12.3 yrs from a population of Han Nationality in Chengdu area. The results showed that the frequencies of apoE phenotypes and alleles were: E3/3 72.93%, E2/3 12.98%, E3/4 11.33%, E2/4 1.38%, E4/4 1.38%, E2/2 0.00%; epsilon 3 0.8508, epsilon 2 0.0718, epsilon 4 0.0774. The results also showed that the apo E2(E2/3 + E2/2) group had lower levels of serum TC and apoB100 (P < 0.05) and a higher level of serum apoE (P < 0.001) when compared with the apoE3(E3/3) or apoE4(E3/4 + E4/4) group. No significant difference was observed in TG, apoA I, apoC II, and apoC III levels among the apoE2, E3 and E4 groups (P > 0.05).

Adult↗

Clinical analysis of 69 patients with familial benign chronic pemphigus.

OBJECTIVE: To analyze the clinical feature, efficacy of treatment and prognosis in familial benign chronic pemphigus (FBCP). METHODS: Sixty-nine cases of FBCP were retrospectively analyzed. RESULTS: The ratio of male to female is 3.93:1 in 69 patients (55 males, 14 females). The mean age at the onset was 29.09 years (3-60 years). There was familial history in 27 families in all of the cases. The lesion usually involved in genital area, neck, axillae and popliteal fossa. Erythemas and vesicles on the soles were seen only in 1 case. Histopathologically 44 cases had special features of FBCP, and immunopathologically 8 cases were direct immunofluorescence (DIF) negative, in which one case had C3 linear deposition along dermoepidermal junction. The combined regimen was more effective. The low-dose X-ray could improve the effect. CONCLUSION: The disease is transmitted as an irregular autosomal dominant trait. The condition in males is more frequent than that in females, probably owing to the different level of female hormone in both sexes. Our patients have the same clinical features as those reported in the literature, but the erythema, vesicle lesions on sole have not been documented in the literature. The combined therapy should be adopted in this condition.

Adult↗

[Origin and progress of myelodysplastic syndrome with hypoplasia].

OBJECTIVE: To study the origin and progress of myelodysplastic syndrome (MDS) with hypoplasia. METHODS: The data of twenty-five cases of hypomyeloplastic MDS diagnosed by our department in the last ten years were analyzed. 17 of the 25 cases were followed up for a long time. RESULTS: (1) The percentage of hypomyeloplastic MDS was 11.4% of the total 219 MDS patients. The median age of the 25 cases was (44.8 +/- 14.7) years. (2) FAB subtype: There were 11 cases of RA and 14 of RAEB. (3) Hypomyeloplastic MDS seems to be a developmental phase in the clinical course in some of the patients and not a special type of MDS. Hyper- and hypo-myeloplasia could be transformed from one to another. The transformation of myelodysplasia could occur either in the same or and different FAB subtype. (4) Seven of the seventeen cases transformed to acute leukemia (41.2%), 6 cases were AML and 1 was ALL. 3 of the 7 cases transformed to hypomyeloplastic leukemia and the remaining 4 transformed to hypermyeloplastic leukemia. (5) The median time from the diagnosis of RAEB to leukemia transformation, was 27 months in 7 cases with hypoplastic RAEB. (6) No relationship was found between therapeutic medicines and development of hypomyeloplastic MDS. CONCLUSION: It is suggested that hypomyeloplastic MDS is probably a developmental phase in the clinical course of MDS, but not a special type.

Adult↗