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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
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

[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↗
PubMed1999

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↗
PubMed1999

[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↗
PubMed1999

[Comparison of subclinical infection rates between vaccinated group with type I inactivated vaccine against hemorrhagic fever and controls].

OBJECTIVE: To compare subclinical infection rate in the vaccinated group with type I inactivated vaccine against hemorrhagic fever with renal syndrome (HFRS) with that in the controls and to understand its enhancement. METHODS: A trial field was selected in Jiande County, Zhejiang Province during July 1974 to November 1997. Paired-sera before and after vaccination were collected from 401 vaccinee and 360 controls, respectively. Serum titer of indirect immunofluorescent IgG antibody (IFAT) against HFRS was detected for each of them, and its cut-off value depended on the distribution of serum antibody titer in the second determination in the controls, which could be used to evaluate subclinical infection before vaccination. RESULTS: There was no significant difference in subclinical infection between those with positive and negative IFAT before vaccination, with different cut-off values for identifying subclinical infection. In both vaccinated and control groups with negative IFA before vaccination, subclinical infection rate was 7.62% in the controls, and 2.17% and 1.63% in the vaccinated ones, with cut-off values of 1:160 and 1:320, respectively, significantly different from that in the former. Subclinical infection rate was 11.38% and 6.78% in the vaccinated ones, as cut-off values of 1:20 and 1:40, respectively, without significant difference from the controls. CONCLUSION: No increase in subclinical infection in the vaccinated group with type I inactivated vaccine against HFRS was found.

Adolescent↗
PubMed1999

[A study on immunogenicity and safety of bivalent inactivated vaccine against hemorrhagic fever with renal syndrome].

OBJECTIVE: To study side effects and effectiveness of bivalent inactivated vaccine against hemorrhagic fever with renal syndrome in population of a randomized controlled field trial. METHODS: Serum indirect immunofluorescent antibody in 167 persons and neutralization antibody (types I and II) in 69 persons, who received three-dose vaccine, were determined two weeks after immunization, and side effects in 657 vaccinees were observed within 72 houses after immunization. RESULTS: Serum positive conversion rate of indirect immunofluorescent antibody was 99.04% (166/167) with GMT of 24.51 +/- 2.06. Serum positive conversion rate of neutralization antibody was 100% (69/69), 91.30% (63/69) for types I and 88.41% (61/69) for type II, respectively. GMTs for type I and II neutralization antibody were 18.27 +/- 2.21 and 12.47 +/- 2.16, respectively. Side effects at local site vaccinated of the body and temperature rising could be seen in 1.48% and 0.36% of the vaccinees, respectively. No severe side effect and abnormal reaction was found in vaccinees on the field. CONCLUSION: Immune response to bivalent inactivated vaccine against hemorrhagic fever with renal syndrome was satisfactory with slight side effect.

Adolescent↗
PubMed1999

[Establishment of a chemotherapeutic agents-induced apoptosis model of retinoblastoma].

OBJECTIVE: To determine the apoptotic effects of different chemotherapeutic agents on the retinoblastoma(RB) cell line HXO-RB44 and to establish a drug-induced apoptosis model of RB in vitro as the basis for further research on the mechanism of drug-induced apoptosis and spontaneous regression of RB. METHODS: Twelve chemotherapeutic agents, including vincristine, cytarabin, methotrexate, cyclophosphamide, thiotepa, mitoxantrone, aclanomycin, pirarubicin, cisplatin, carboplatin, mitomycin, etoposide, of different concentration (10(-9), 10(-8), 10(-7), 10(-6), 10(-5), 10(-4) mol.L-1) were employed into HXO-RB44 cell line respectively for 24 hours, then apoptotic effects on it were decided by observing the DNA ladders on agarose gel electrophoresis. After that, one chemotherapeutic agent with the most evident DNA ladders was applied into HXO-RB44 cell line for 4, 8, 16, 24, 48 and 72 hours respectively, and the DNA ladders on agarose gel were also surveyed. Apoptotic cells were identified with transmission electron microscopy. RESULTS: Typical DNA ladders were shown on agarose gel after HXO-RB44 cell line were exposed to 10(-6)-10(-5) mol.L-1 vincristine and 10(-5) mol.L-1 aclanomycin for 24 hours and the former were much clearer. No DNA ladders did emerge when the RB cells were treated by the rest ten chemotherapeutic agents. The DNA ladders began to appear when dealt with 10(-5) mol.L-1 vincristine for 8 hours, to be most obvious for 24 hours, and abated for 48 hours then disappeared for 72 hours. Amount of apoptotic RB cells were observed by transmission electron microscopy. CONCLUSION: Both vincristine and aclanomycin have the effect of inducing apoptosis on HXO-RB44 cell line, but that of vincristine is more forceful, which is time and concentration dependent. So vincritine is an ideal agent for establishing an apoptosis model of HXO-RB44 cell line.

Antineoplastic Agents↗
PubMed1999

[Cloning and sequencing of human papillomavirus 16 L1 gene from cervical carcinoma tissues of Chinese women].

OBJECTIVE: Human papillomavirus type 16 (HPV16) is highly related with the development of cervical carcinoma. HPV16 late gene L1 encodes its main capsid protein. This study is to analyze the whole sequence of L1 gene of HPV16 of the Chinese isolates. METHODS: Three samples of HPV16 L1 gene were amplified from cervical carcinoma tissues of Chinese patients by PCR and then cloned and sequenced. RESULTS: There were four sites in nucleic acid sequences of all three HPV16 L1 fragments were different from the originally reported sequence of HPV16 and the differed sequences had changed the triplet codes, therefore, subsequently changed the amino acids it coded. CONCLUSION: The results showed that some mutation had taken place in the nucleotide sequence of L1 gene of HPV16 obtained from the cervical carcinoma tissues of Chinese women.

Capsid Proteins↗
PubMed1998

Altered thymic positive selection and intracellular signals in Cbl-deficient mice.

Cbl is the product of the protooncogene c-cbl and is involved in T cell antigen receptor (TCR)-mediated signaling. To understand the role of Cbl for immune system development and function, we generated a Cbl-deficient mouse strain. In Cbl-deficient mice, positive selection of the thymocytes expressing major histocompatibility complex class II-restricted transgenic TCR was significantly enhanced. Two factors may have contributed to the altered thymic selection. First, Cbl deficiency markedly up-regulated the activity of ZAP-70 and mitogen-activated protein kinases. The mitogen-activated protein kinase pathway was shown previously to be involved in thymic positive selection. Second, Cbl-deficient thymocytes expressed CD3 and CD4 molecules at higher levels, which consequently may increase the avidity of TCR/major histocompatibility complex/coreceptor interaction. Thus, Cbl plays a novel role in modulating TCR-mediated multiple signaling pathways and fine-tunes the signaling threshold for thymic selection.

Animals↗
PubMed1998

Mitotic index and Alzheimer's disease.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is diagnosed definitively by increased numbers of beta-amyloid plaques and neurofibrillary tangles in brain biopsy or autopsy specimens. There are no simple straightforward laboratory tests currently available for clinical diagnosis. We have found consistent reduction in mitotic index levels in skin fibroblast cultures from AD individuals compared with age- and sex-matched controls. These differences were enhanced by overnight exposure to colcemid (p = 0.04). Results suggest that mitotic index in skin fibroblasts cultures should be further investigated as a potential diagnostic indicator for AD.

Aged↗
PubMed1998

Normal adaptive function with learning disability in duplication 8p including band p22.

Duplication 8p usually results in a syndrome characterized by profound mental retardation, mild facial anomalies, and malformations of hand, heart, and brain. We report on a large kindred segregating a Y;8 translocation in whom several individuals have duplication 8p22-->8pter. These individuals have normal adaptive function despite their unbalanced karyotype. The family was studied with G-banding and fluorescent in situ hybridization (FISH) using probes to chromosomes 8 and Y. Comparison of this family with other reported cases defines a mild clinical outcome for trisomy 8p22-->8pter in contrast to the severe findings when the duplication involves a longer, more proximal segment.

Adaptation, Physiological↗
PubMed1998

Identification of a candidate human spectrin Src homology 3 domain-binding protein suggests a general mechanism of association of tyrosine kinases with the spectrin-based membrane skeleton.

Spectrin is a widely expressed protein with specific isoforms found in erythroid and nonerythroid cells. Spectrin contains an Src homology 3 (SH3) domain of unknown function. A cDNA encoding a candidate spectrin SH3 domain-binding protein was identified by interaction screening of a human brain expression library using the human erythroid spectrin (alphaI) SH3 domain as a bait. Five isoforms of the alphaI SH3 domain-binding protein mRNA were identified in human brain. Mapping of SH3 binding regions revealed the presence of two alphaI SH3 domain binding regions and one Abl-SH3 domain binding region. The gene encoding the candidate spectrin SH3 domain-binding protein has been located to human chromosome 10p11.2 --> p12. The gene belongs to a recently identified family of tyrosine kinase-binding proteins, and one of its isoforms is identical to e3B1, an eps8-binding protein (Biesova, Z., Piccoli, C., and Wong, W. T. (1997)Oncogene 14, 233-241). Overexpression of the green fluorescent protein fusion of the SH3 domain-binding protein in NIH3T3 cells resulted in cytoplasmic punctate fluorescence characteristic of the reticulovesicular system. This fluorescence pattern was similar to that obtained with the anti-human erythroid spectrin alphaI SigmaI/betaI SigmaI antibody in untransfected NIH3T3 cells; in addition, the anti-alphaI SigmaI/betaI SigmaI antibody also stained Golgi apparatus. Immunofluorescence obtained using antibodies against alphaI SigmaI/++betaI SigmaI spectrin and Abl tyrosine kinase but not against alphaII/betaII spectrin colocalized with the overexpressed green fluorescent protein-SH3-binding protein. Based on the conservation of the spectrin SH3 binding site within members of this protein family and published interactions, a general mechanism of interactions of tyrosine kinases with the spectrin-based membrane skeleton is proposed.

3T3 Cells↗
PubMed1998

The sequences of small proteins are not extensively optimized for rapid folding by natural selection.

The thermodynamic stabilities of small protein domains are clearly subject to natural selection, but it is less clear whether the rapid folding rates typically observed for such proteins are consequences of direct evolutionary optimization or reflect intrinsic physical properties of the polypeptide chain. This issue can be investigated by comparing the folding rates of laboratory-generated protein sequences to those of naturally occurring sequences provided that the method by which the sequences are generated has no kinetic bias. Herein we report the folding thermodynamics and kinetics of 12 heavily mutated variants of the small IgG binding domain of protein L retrieved from high-complexity combinatorial libraries by using a phage-display selection for proper folding that does not discriminate between rapidly and slowly folding proteins. Although the stabilities of all variants were decreased, many of the variants fold faster than wild type. Taken together with similar results for the src homology 3 domain, this observation suggests that the sequences of small proteins have not been extensively optimized for rapid folding; instead, rapid folding appears to be a consequence of selection for stability.

Bacterial Proteins↗
PubMed1998

Effectiveness of ischemic preconditioning on long-term myocardial preservation.

BACKGROUND: This study was designed to assess whether the protective effect of ischemic preconditioning can be adapted for myocardium undergoing 6 hr of ischemia. METHODS: Eighteen isolated rat hearts were perfused with oxygen-bicarbonated Krebs-Henseleit buffer in the Langendorff mode for 35 min (group A, controls) or perfused in the Langendorff apparatus for 20 min, followed by 5 min of global normothermic ischemia and 10 min of buffer perfusion (group B, preconditioning) or followed by two cycles of 2.5 min of global normothermic ischemia plus 5 min of buffer perfusion (group C, preconditioning). The hearts were then arrested and preserved for 6 hr with Bretschneider's histidine-tryptophan-potassium cardioplegic solution at 4 degrees C, followed by 30 min of reperfusion. Recovery of cardiac function, postischemic enzyme leakage, and intracellular calcium concentration were compared. RESULTS: After 6 hr of ischemia, the hearts that underwent preconditioning in groups B and C showed better recovery of left ventricular developed pressure (P<0.05), a lower end-diastolic pressure level (P<0.05), less leakage of creatine kinase, and a lower intracellular calcium concentration than those in group A. There were no statistical differences in the rate of recovery of coronary flow. CONCLUSIONS: Our study demonstrated that ischemic preconditioning improves myocardial functional recovery after 6 hr of hypothermic preservation in the isolated rat heart. Preconditioning might be useful for preserving the heart against long-term ischemia/reperfusion injury.

Animals↗