Search PubMed⌕ Search

Biomedical subjects

D Huang

Publications and source records attributed to D Huang.

At least 199 records · Page 11Linked to original sources

Influence of the susceptibility genes apolipoprotein E-epsilon 4 and apolipoprotein E-epsilon 2 on the rate of disease expressivity of late-onset Alzheimer's disease.

Apolipoprotein E-epsilon 4 (APOE4, gene; apoE4, protein) is a susceptibility gene or risk factor for Alzheimer's disease. The genetic relevance of APOE4 has been widely confirmed. The APOE gene is not a disease locus, with specific mutations causing Alzheimer disease. Allelic variations at the APOE locus affect the rate of disease progression. The association of specific inherited APOE alleles with age of onset distributions describes biological effects based on genotype. The inheritance of polymorphic genes with single amino acid differences between apoE4 and apoE3 (and between apoE3 and apoE2) at the protein level is associated with differences in the mean age of disease onset spanning almost two decades. The isoform-specific metabolism of apoE resulting in a faster rate of disease expression can now be studied with the expectation that genetically relevant processes are being investigated. There is now an opportunity to develop theories directed at the genetically relevant apoE metabolism that can significantly delay disease expression.

Age of Onset↗

[Evaluation of the prognosis of critically ill surgical patients by APACHE II score system].

A prospective trial was conducted in 386 critically ill surgical patients, the APACHE II score was used to quantify the severity of illness and to judge the outcome. Admission APACHE II score of these patients averaged 15.6 +/- 5.4, the mortality rates rose from 1.9% to 100% when the APACHE II score increased from 0 to 38. The score was closely correlated with the subsequent risk of hospital death for these patients (r = 0.75 P < 0.001). Critically ill surgical patients would be well served by APACHE II for quality assurance or outcome.

APACHE↗

[Nationwide survey of the distribution of human parasites in China--infection with parasite species in human population].

The infection rate of main species of parasites and their character by first nationwide survey of human parasites was made. The overall infection rate of human intestinal parasite and the infection rate of most species of parasites were higher in females than that in males. The infection rate according to the age group, the highest infection rate was found in the group aged 5-14 years. With regard to the relation between parasitic infections and occupations of the infected persons, the highest infection rates of Ascaris lumbricoides were exhibited in school children, of hookworm and Clonorchis sinensis were in halfpeasants and halfmerchant and vegetable grower; of Trichuris trichiura were in fishers, of Giardia lamblia, Entamoeba histolytica and Taenia were in herdsmen and halfherdsmen and halfpeasants. In this survey it is also shown that each nationality has their main species of parasites. The family clustering of some main parasites were proved by some province/autonomous region/municipality.

Adolescent↗

[Relationship between the rate of parasitic infection and the knowledge of prevention].

The relationship between the rate of parasitic infection and the level of knowledge of prevention was studied among 5479 persons allocated to 12 randomly selected groups. Stools were examined for parasitic infection by using Kato-Katz, iodine direct smear amd tube culturing methods. Children under 15 were examined for Enterobius infection by cellophane tape method. Individuals were considered infected when any parasite species was found in the stool and the infection rate was computed. The score on knowledge of prevention was measured by devising a questionnaire comprising 11 questions on parasitic disease transmission, clinical signs and prevention methods. Ten marks were given for each question correctly answered. The result of the investigation showed that the total infection rate was 52.2% and there was no significant difference between males and females (X2 = 1.94, P > 0.05). The infection rate increased with a decrease in the level of education and the highest was found in 5-year-old age group. There were altogether 7 species of parasites detected in all age groups. The infection rate of Ascaris lumbricoides was 31.3%; Trichuris trichiura, 34.1%; hookworm, 5.3%; Enterobius vermicularis, 20.3%(227+1 117); Fasciolopsis buski, 0.8%; Entamoeba coli, 0.8%; Giardia lamblia, 0.2%. The average score on knowledge was 41.9, being significantly higher in males than in females. Analysis for the age distribution showed that the highest score was found in 15-year-old age group. The data of infection rate of different parasites were converted by arcsine transformation and compared with the average score, showing that there were negative relations between the average score and the infection rate of Trichuris, hookwork, Entamoeba and the total incidence. The value of r was --0. 5534, --9.5557, --0.6091 and --0.604. respectively. The number of parasite species infecting individuals was also found to have negative relation to the score on knowledge of prevention.

Adolescent↗

[Surgical treatment of space-occupying lesions in the nasal cavity and paranasal sinus involving the skull base].

This paper reports 29 cases of space-occupying lesions in the nasal cavities and the paranasal sinuses. Of them, 12 were benign and 17 malignant. They were all surgically treated, 17 by lateral rhinotomy, 6 by combined cranio-nasal approaches, 3 by maxillectomy and evisceration of the orbit, 1 by transfrontal and 1 by midfacial degloving approaches, respectively. The regional chemotherapy was administered to a case via external carotid artery after neck dissection. Among these cases, 18 of the skull defects were rehabilitated. The repairing materials included the autologous perpendicular plate of the ethmoid bone, the vomer, the septal cartilage, the middle turbinate and the internal laminae of the frontal bone or sinus. The meningeal defects in 14 cases were repaired using autologous muscle, fascia, galea aponeurotica. Except for one case of postoperative cerebrospinal rhinorrhea due to improper surgical approach, no cases had postoperative complications.

Adolescent↗

[Clinical study on allogenic conjunctival transplantation].

PURPOSE: To investigate the indications and outcome of human allogenic conjunctival transplantation. METHODS: The necrotic tissues and scars were removed from the fornix by using the residual conjunctiva. Then the allograft without Tenon's capsule was transplanted to cover the wound. RESULTS: At 6 postoperative months, the surface was completely healed in 76%x. For patients with mechanical trauma or thermal burn, the area of transplanted conjunctiva was less than one third, or using donor conjunctiva from parents or siblings are of better prognossis. CONCLUSIONS: 1) Allogenic conjunctival transplantation is a feasible treatment for servere symblephron and lid defects. 2) The result is poor when residual conjuctiva is less than 1/2. 3) The outcome is best in mechanical trauma and worst in alkaline burns, with thermal burns somewhere in between. 4) The simple bulbal conjunctival transplantation has better results.

Adolescent↗

Differential effects of monoclonal antibodies on activating transcription factor-1 and cAMP response element binding protein interactions with DNA.

Activating transcription factor-1 (ATF1) and cAMP response element binding protein (CREB) have been implicated in cAMP-, calcium-, and virus-induced transcriptional alterations. Although CREB and ATF1 share extensive homology, they appear to mediate distinct cellular functions. We investigated the effect on DNA binding and in vitro transcription of four monoclonal antibodies (mAb) that bound to domains in either the regulatory region (mAb 1 and 3) or unique regions near the DNA-binding domains (mAb 4 and 5) of ATF1.mAb 1 and 3 supershifted both ATF1 and CREB in a DNA binding assay but did not affect in vitro transcription. mAb 4 prevented ATF1-DNA binding while supershifting CREB.DNA complexes and inhibited in vitro transcription by 95% from the CRE-containing murine proliferating cell nuclear antigen promoter. mAb 5 reacted specifically with ATF1 and did not prevent DNA binding or affect in vitro transcription. The mAb 4 epitope was located within ATF1 amino acid residues 205-219, including the first 3 basic residues in the putative DNA-binding domain. Secondary structural analysis predicted that this region comprises a transition site from alpha-helix to a turn-like conformation in ATF1. The transition to turn-like motifs is predicted to occur in CREB after 5 additional residues, with a correspondingly longer alpha-helical domain. Although regulatory domains distinct from DNA binding regions are thought to account for most of the differences in activity of members of the CREB subfamily, our results suggest that small structural variations adjacent to DNA binding regions may also contribute to the distinct functional activities of ATF1 and CREB.

Activating Transcription Factor 1↗

Analysis of the rat lactate dehydrogenase A subunit gene promoter/regulatory region.

The rat lactate dehydrogenase (LDH) A subunit gene promoter contains a putative AP-1 binding site at -295/-289 bp, two consensus Sp1 binding sites at -141/-136 bp and -103/-98 bp, and a single copy of a consensus cyclic AMP-responsive element (CRE) at -48 to -41 bp upstream of the transcription initiation site. Additionally, an as yet unidentified silencer element is located within the -1173/-830 bp 5'-flanking region. Transient transfection analyses of a -1173/+25 bp LDH A-chLoramphenicol acetyltransferase fusion gene has indicated a complete inability of the promoter fragment to direct basal or forskolin-induced transcription. Deletion of the -1173/-830 bp sequence restored basal and cyclic AMP (cAMP)-inducible activity. Point mutations in the Sp1 binding sites of a -830/+25 bp promoter fragment reduced basal but not the relative degree of cAMP-inducible activity. cAMP-regulated transcriptional activity was dependent upon an 8 bp CRE, -TGACGTCA-, located at the -48/-41 bp upstream region. Mutations in the CRE abolished cAMP-mediated induction and reduced basal activity by about 65%. The CRE binds a 47 kDa protein which has previously been identified as CRE binding protein (CREB)-327, an isoform of the activating transcription factor/CREB transcription factor gene family. Co-transfection of a vector that expresses the catalytic subunit of cAMP-dependent protein kinase stimulates LDH A subunit promoter activity suggesting that cAMP induces LDH A subunit gene expression through phosphorylative modification of CREB-327. This study emphasizes a fundamental role of several modules including Sp1 and CREB binding sites in regulating basal and cAMP-mediated transcriptional activity of the LDH A gene.

Animals↗

Interactions between cAMP-dependent and SNF1 protein kinases in the control of glycogen accumulation in Saccharomyces cerevisiae.

The synthesis of glycogen in Saccharomyces cerevisiae is stimulated by nutrient limitation and requires both glycogen synthase and the glycogen branching enzyme. Of the two glycogen synthase genes present in yeast, GSY2 appears to be more important for the accumulation of glycogen upon entry into stationary phase. In cells grown on glucose, GSY2 mRNA levels increased approximately 10-fold during the transition from logarithmic to stationary phase. Growth of cells in glycerol, however, resulted in constitutive expression of GSY2 mRNA and the corresponding protein, GS-2, suggestive of glucose repression of GSY2. Mutants defective in the SNF1 gene, which encodes a protein kinase important in glucose repression mechanisms, are known not to accumulate glycogen. A modest 2-4-fold decrease in total GS-2 level was observed, and upon entry into stationary phase, the enzyme was blocked in the inactive, phosphorylated state in snf1 strains. The GS-2 protein is thought to be regulated by covalent phosphorylation of three COOH-terminal sites (Hardy, T.A., and Roach, P.J. (1993) J. Biol. Chem. 268, 23799-23805), removal of which results in constitutively active glycogen synthase that bypasses phosphorylation controls. Expression of COOH-terminally truncated GS-2 in snf1 cells restored glycogen accumulation, and so we propose that the SNF1 kinase controls the phosphorylation state of GS-2. Cyclic AMP pathways also exert control over glycogen accumulation. In bcy1 cells, which have constitutively active cyclic AMP-dependent protein kinase, greatly reduced levels of both GS-2 message and protein were observed. With wild type GSY2 placed under control of the ADH1 promoter, bcy1 cells did not accumulate glycogen despite increased GS-2. Overexpression of truncated GS-2, however, resulted in definite though reduced glycogen accumulation; the glycogen synthesized was structurally distinct from wild type with properties characteristic of less branched polysaccharide. We conclude that the cAMP pathway controls both the expression and the phosphorylation state of GS-2. Furthermore, other factor(s) necessary for glycogen biosynthesis, such as the branching enzyme GLC3, must also be under negative control by the cAMP pathway. The results demonstrate interactive controls of GS-2 by the cAMP-dependent and SNF1 protein kinases.

Alcohol Dehydrogenase↗

Genetic and physiological association of diabetes susceptibility with raised Na+/H+ exchange activity.

Insulin-dependent diabetes mellitus is a multigenic autoimmune disease, for which one of the best animal models is the nonobese diabetic (NOD) mouse strain. In both humans and NOD mice, major histocompatibility complex genes are implicated as risk factors in the disease process. Other susceptibility genes are also involved, and a number have been mapped in the mouse to specific chromosomal locations. To identify further susceptibility genes, diabetic backcross mice, produced after crossing NOD/Lt to the nondiabetic strains SJL and C57BL/6 (B6), were examined for markers not previously associated with disease susceptibility. Linkage was found to loci on chromosomes 4 and 14. Of the candidate loci on chromosome 4, the gene encoding the Na+/H+ exchanger-1, Nhe-1, was the most likely, since the NOD allele was different from that of both nondiabetic strains. NOD lymphocytes were found to have a higher level of Na+/H+ exchange activity than lymphocytes from either B6 or SJL mice. Since the chromosome 4 susceptibility gene is recessive, the B6 allele should prevent diabetes. This prediction was tested in fourth-generation backcross mice, selected for retention of the B6 allele at Nhe-1. Mice homozygous for Nhe-1 developed diabetes after cyclophosphamide treatment, but heterozygotes were largely protected from disease. These results implicate the Na+/H+ exchanger (antiporter) in the development of type 1 diabetes and may provide a screening test for at-risk individuals as well as offering prospects for disease prevention.

Alleles↗

Characterization of the chloroplast cytochrome b6f complex as a structural and functional dimer.

Size analysis of the cytochrome b6f complex by FPLC Superose-12 chromatography and Blue Native PAGE indicated a predominantly dimeric component with M(r) = (1.9-2.5) x 10(5). The true dimer molecular weight including bound lipid, but not detergent, was estimated to be 2.3 x 10(5). Size and shape analysis by negative-stain single-particle electron microscopy indicated that the preparation of dimeric complexes contains a major population that has a protein cross section 40% larger than the monomer, binds more negative stain, and has a geometry with a distinct 2-fold axis of symmetry compared to the monomeric complex. The dimeric species is more stable at higher ionic strength with respect to conversion to the monomeric species. SDS-PAGE of monomer and dimer preparations indicated that both contain the four major polypeptides in approximately equal stoichiometry and also contain the petG M(r) 4000 subunit. One bound chlorophyll a per monomer, part of the bound lipid, is present in monomer and dimer. The in vitro electron-transport activity (decyl-PQH2-->PC-ferricyanide) of the separated dimer was comparable to that of the isolated b6f complex and was 4-5-fold greater than that of the monomer preparation, whose activity could be attributed to residual dimer. No difference in the properties of the dimer and monomer was detected by SDS-PAGE or redox difference spectrophotometry that could account for the difference in activities. However, the concentration of the Rieske [2Fe-2S] center was found by EPR analysis of the gy = 1.90 signal to be lower in the monomer fraction by a factor of 3.5 relative to the dimer.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopolymers↗

Crystal structure of chloroplast cytochrome f reveals a novel cytochrome fold and unexpected heme ligation.

BACKGROUND: Cytochrome f is the high potential electron acceptor of the chloroplast cytochrome b6f complex, and is the electron donor to plastocyanin. The 285-residue cytochrome f subunit is anchored in the thylakoid membrane of the chloroplast by a single membrane-spanning segment near the carboxyl terminus. A soluble redox-active 252-residue lumen-side polypeptide with native spectroscopic and redox properties, missing the membrane anchor and carboxyl terminus, was purified from turnip chloroplasts for structural studies. RESULTS: The crystal structure of cytochrome f, determined to 2.3 A resolution, has several unexpected features. The 252-residue polypeptide is organized into one large and one small domain. The larger heme-binding domain is strikingly different from known structures of other c-type cytochromes and has the same fold as the type III domain of the animal protein, fibronectin. Cytochrome f binds heme with an unprecedented axial heme iron ligand: the amino terminus of the polypeptide. CONCLUSION: The first atomic structure of a subunit of either the cytochrome b6f complex or of the related cytochrome bc1 complex has been obtained. The structure of cytochrome f allows prediction of the approximate docking site of plastocyanin and should allow systematic studies of the mechanism of intra- and inter-protein electron transfer between the cytochrome heme and plastocyanin copper, which are approximately isopotential. The unprecedented axial heme iron ligand also provides information on the sequence of events (i.e. cleavage of signal peptide and ligation of heme) associated with translocation of the cytochrome across the membrane and its subsequent folding.

Amino Acid Sequence↗

Micrometer-scale resolution imaging of the anterior eye in vivo with optical coherence tomography.

OBJECTIVE: To demonstrate a new diagnostic technique, optical coherence tomography, for high-resolution cross-sectional imaging of structures in the anterior segment of the human eye in vivo. Optical coherence tomography is a new, noninvasive, noncontact optical imaging modality that has spatial resolution superior to that of conventional clinical ultrasonography (< 20 microns) and high sensitivity (dynamic range, > 90 dB). DESIGN: Survey of intraocular structure and dimension measurements. SETTING: Laboratory. PATIENTS: Convenience sample. MAIN OUTCOME MEASURES: Correlation with range of accepted normal intraocular structure profiles and dimensions. RESULTS: Direct in vivo measurements with micrometer-scale resolution were performed of corneal thickness and surface profile (including visualization of the corneal epithelium), anterior chamber depth and angle, and iris thickness and surface profile. Dense nuclear cataracts were successfully imaged through their full thickness in a cold cataract model in calf eyes in vitro. CONCLUSIONS: Optical coherence tomography has potential as a diagnostic tool for applications in noncontact biometry, anterior chamber angle assessment, identification and monitoring of intraocular masses and tumors, and elucidation of abnormalities of the cornea, iris, and crystalline lens.

Anterior Chamber↗

Hypothesis: microtubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype.

A genetic classification of Alzheimer disease(s) (AD) is presented. We describe a potential metabolic process in individuals who inherit apolipoprotein E-epsilon 4 (APOE4, gene; apoE4, protein) alleles, leading to increased risk and earlier age of onset of late-onset Alzheimer disease. Apolipoprotein E-epsilon 3 (apoE3) binds to tau protein, possibly slowing the initial rate of tau phosphorylation and self-assembly into paired helical filaments (PHFs); apoE4 does not bind tau. Tau promotes microtubule assembly and stabilizes microtubules; hyperphosphorylated tau does not bind, thereby destabilizing microtubules. Hyperphosphorylated tau may self-assemble into PHFs. Over time a bias toward destabilization of microtubules and the formation of neurofibrillary tangles may occur in individuals who inherit APOE4 alleles, leading to a shorter functional neuronal life span. This hypothesis focuses attention on two important aspects of AD research design: (1) Although the inheritance of APOE4 is associated with increased risk and decreased age of onset, apoE4 does not directly cause the disease. Our data point to the absence of an important function of apoE3 or apoE2 in individuals who do not inherit these alleles as the genetically relevant metabolic factor. This has important implications for design of experiments directed toward understanding the relevant neuronal metabolism. (2) Should this hypothesis be proven and confirmed, targets for pharmaceutical therapy designed to mimic the metabolic function of apoE3 or apoE2 become a realistic preventive strategy.

Alzheimer Disease↗