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Biomedical subjects

Min Yao

Publications and source records attributed to Min Yao.

At least 73 records · Page 4Linked to original sources
PubMed2005

[Coronary angiography and clinical characteristics of ventricular septal rupture after acute myocardial infarction].

OBJECTIVE: To provide evidence for the prevention and treatment of ventricular septal rupture (VSR) after acute myocardial infarction (AMI) by analyzing clinical and coronary angiographical characteristics. METHODS: Data on clinical and angiographical characteristics, effects of medical and surgical treatment and survival rate in 46 patients with VSR were analyzed retrospectively using statistical SPSS 11.0 software. RESULTS: The incidence of VSR after AMI was 1.88%. The susceptible risk factors were advanced age, no reperfusion therapy, no previous angina/myocardial infarction, complicated with hypertension/hyperlipidemia, etc. The most common location of myocardial infarction was anterior wall together with inferior wall. Percentage of neutrophil, serum level of CRP and ESR increased in most cases. Pulmonary edema (by X-ray) occurred in 30 percent of the cases, and 50 percent of the cases had unstable hemodynamics (Killip III-IV). In cases with anterior wall related infarction, the location of rupture was usually at distal area of anteroseptal, and in cases with inferior wall together with posterior/right wall infarction, it was usually at basal posteroseptal. By coronary angiography, most of the patients were with single vessel or 3-vessel coronary disease, rarely with collateral circulation. Left anterior descending coronary was the most common criminal vessel, especially in its middle segment. In-hospital mortality was 65% by conservative therapy while it was 3.85% by surgical treatment. CONCLUSION: Early and successful revascularization is the key factor for the prevention of VSR after AMI. Echocardiography is a sensitive and simple method for diagnosis. Surgical treatment improves the survival rate significantly. Early surgery is feasible.

Aged↗
PubMed2004

A new generation organ culture arising from cross-talk between multiple primary human cell types.

The inability to experiment directly on humans strongly constrains biomedical research, creating a great need to develop cultures that mimic human tissues and organs as experimental systems that can be used to directly understand and manipulate biological processes. The advent of availability of primary human cells now makes possible engineering of such organ cultures. Here we report the generation of a human "skin" arguably the simplest human tissue. Beginning with three primary cell types taken from adult tissues, this organ culture develops into a mature tissue containing a stratified epithelium and an interconnected network of mature microvessels, with appropriate matrix molecules and cytokines. Surprisingly, pericytes and monocytes appear adjacent to and within "blood" vessels, respectively. These cultures respond appropriately to stimulators of specific biological processes, providing a vehicle to investigate basic biological processes, such as 1) cell-cell and cell-microenvironment interaction; 2) transdifferentiation of one cell type to another and/or differentiation from stem cells present in adult tissues; and 3) opportunities for genetic manipulation of human tissues to understand function. Moreover, this "skin" can potentially be developed into a tailored "living bandage" for patients with impaired healing and can serve as prototype for the development of other human organ cultures.

Capillaries↗
PubMed2004

cCXCR1 is a receptor for cIL-8 (9E3/cCAF) and its N- and C-terminal peptides and is also activated by hIL-8 (CXCL8).

Chemokines are chemotactic cytokines that play important roles in immune responses and wound healing, as well as in pathological conditions such as chronic inflammation and tumorigenesis. The chemokines and their receptors are highly conserved and maintain similar functions in different species. One noteworthy exception is the chemokine interleukin (IL)8/CXC ligand 8 and its specific receptor CXCR1, which are found in humans but are not found in the traditional model organisms, mice and rats. As a consequence, we are using model organisms other than mice to study the functions of IL-8 and CXCR1, as well as the mechanisms involved in receptor activation by IL-8. Toward this goal, we have isolated and characterized a new receptor that is highly homologous to human (h)CXCR1, which we named chicken (c)CXCR1. To determine whether this receptor is activated by cIL-8 and its N- and C-terminal peptides and whether it responds to hIL-8, we expressed cCXCR1 in NIH3T3 cells, which naturally lack this receptor, and used single-cell Ca(2)(+) imaging to detect increases in intracellular Ca(2)(+) and immunoblot analysis to detect extracellular signal-regulated kinase 1/2 phosphorylation. We show that cIL-8, its N and C peptides, and hIL-8 activate cCXCR1. We further show that cIL-8 and hIL-8 stimulate chemotaxis of chicken embryonic fibroblasts, cells that express cCXCR1, and that this effect is specific for each chemokine and this receptor. These results strongly suggest that cCXCR1 is the ortholog for hCXCR1 and that chickens can be used as an effective model system to study the functions of IL-8, its terminal peptides, and its specific receptor CXCR1.

3T3 Cells↗
PubMed2004

Value of FDG PET in assessment of treatment response and surveillance in head-and-neck cancer patients after intensity modulated radiation treatment: a preliminary report.

PURPOSE: [(18)F] fluorodeoxyglucose positron emission tomography (FDG PET) imaging has been shown to be valuable in early detection of persistent and recurrent head-and-neck cancer after treatment. Previous studies have reported its use in patients treated with conventional radiation. Many patients are now treated with intensity-modulated radiation treatment (IMRT). We evaluated the value of FDG PET in the assessment of treatment response and surveillance in head-and-neck cancer patients treated with IMRT. METHODS AND MATERIALS: We performed a retrospective review of 85 head-and-neck cancer patients treated with IMRT at our institution between December 2000 and September 2003 who had FDG PET in their follow-up. Of these, 58 were treated with primary IMRT with or without chemotherapy, and 27 were treated with postoperative IMRT. RESULTS: Sixty-four patients had negative initial FDG PET after treatment. Forty of them, who had 6 to 24 months of follow-up after the imaging study, had no evidence of local or regional recurrence, although three of them developed distant disease. Twenty-one patients had a positive initial FDG PET after treatment, with 11 positive at the primary site, 9 positive in the neck, and 3 positive distantly. Six of 11 patients with a positive FDG PET at the primary site were true positive, and 3 had salvage surgery. Eight of 9 patients positive in the neck had a salvage neck dissection. One had fine needle aspiration of the lymph node with positive cytology but refused surgery later. For patients with follow-up of 6 months and longer, only 1 of 45 patients with a negative initial FDG PET at the primary site developed a local recurrence. None of 49 patients with a negative initial FDG PET in the neck developed a regional recurrence. Two cases are presented in which abnormal FDG PET preceded laryngoscopy or computed tomography in detection of tumor recurrences. CONCLUSIONS: FDG PET is useful in the posttreatment management of head-and-neck cancer patients treated with IMRT. It is highly accurate in the detection of persistent and recurrent disease after treatment and allows salvage treatment to be initiated in a timely manner. It also provides prognostic information concerning the risk of recurrence after curative therapy.

Adult↗
PubMed2004

Crystal structure of the Pyrococcus horikoshii isopropylmalate isomerase small subunit provides insight into the dual substrate specificity of the enzyme.

Recent studies have implied that the isopropylmalate isomerase small subunit of the hyperthermophilic archaea Pyrococcus horikoshii (PhIPMI-s) functions as isopropylmalate isomerase in the leucine biosynthesis pathway, and as homoaconitase (HACN) in the lysine biosynthesis pathway via alpha-aminoadipic acid. PhIPMI is thus considered a key to understanding the fundamental metabolism of the earliest organisms. We describe for the first time the crystal structure of PhIPMI-s, which displays dual substrate specificity. The crystal structure unexpectedly shows that four molecules create an interlocked assembly with intermolecular disulfide linkages having a skewed 222 point-group symmetry. Although the overall fold of the PhIPMI-s monomer is related closely to domain 4 of the aconitase (ACN), one alpha-helix in the ACN structure is replaced by a short loop with relatively high temperature factor values. Because this region is essential for discriminating the structurally similar substrate based on interactions with its diversified gamma-moiety, the loop structure in the PhIPMI-s must be dependent on the presence of a substrate. The flexibility of the loop region might be a structural basis for recognizing both hydrophobic and hydrophilic gamma-moieties of two distinct substrates, isopropylmalate and homocitrate.

Amino Acid Sequence↗
PubMed2004

Structural evidence for guanidine-protein side chain interactions: crystal structure of CutA from Pyrococcus horikoshii in 3 M guanidine hydrochloride.

This study was carried out to investigate the structural perturbation of the protein's local structure by the denaturants under non-denaturing conditions. Crystal structure of CutA from an archaeon Pyrococcus horikosii (PhoCutA), a heavy-metal binding protein, was determined at 1.6-angstroms resolution in the presence of 3 M guanidine HCl (GdnHCl). Native PhoCutA has a large number of short intramolecular hydrogen bonds and salt bridges on the protein surface, of which greater than 90% of hydrogen bonds and all salt bridges were retained in 3 M GdnHCl. Hydrogen bonds that disappeared in the GdnHCl crystal structure were mainly located on the protein surface, especially around the structurally perturbed loop, suggesting interactions between peptide groups and GdnHCl. Only a few GdnH+ ions were observed in the crystal structure, although none at the surface, of the protein. Two GdnH+ ions were observed in the center of the trimeric structure, replacing water molecules, and were hydrogen bonded with Asp84 and Asp86 of each chain. The exterior loop from Tyr39 to Lys44, including Trp40-Trp41, was perturbed structurally. Decreases in temperature factors were observed in beta strand 5 and the N terminus of helix 3. These results suggest the specific bindings of GdnH+ with some acidic residues and the non-specific bindings around Trp residues and peptide groups on the protein surface and that binding of GdnHCl to the native protein is limited, resulting in local structural perturbation.

Archaeal Proteins↗
PubMed2004

Structural and enzymatic properties of 1-aminocyclopropane-1-carboxylate deaminase homologue from Pyrococcus horikoshii.

1-Aminocyclopropane-l-carboxylate deaminase (ACCD) is a pyridoxal 5/-phosphate dependent enzyme that shows deaminase activity toward ACC, a precursor of plant hormone ethylene. ACCD from some soil bacteria has been reported to be able to break the cyclopropane ring of ACC to yield a-ketobutyrate and ammonia. We reported the crystal structure of ACCD from the yeast Hansenula saturnus in the absence/presence of substrate ACC, and proposed its ingenious reaction mechanisms. In order to study the enzyme further, we overexpressed the ACCD homologue protein (phAHP) from the fully decoded hyperthermophilic archearon, Pyrococcus horikoshii OT3. However, phAHP does not show ACCD activity at high temperature as well as at room temperature, though it has significant sequence similarity. Instead of ACCD activity, the GC-MS analysis and enzymatic method show that phAHP has deaminase activity toward L and D-serine. Here, we present the crystal structures of the native and ACC-complexed phAHP. The overall topology of the phAHP structure is very similar to that of ACCD; however, critical differences were observed around the active site. Here, the differences of enzymatic activity between phAHP and ACCD are discussed based on the structural differences of these two proteins. We suggest that the catalytic disagreement between these two enzymes comes from the difference of the residues near the pyridine ring of pyridoxal 5'-phosphate (PLP), not the difference of the catalytic residues themselves. We also propose a condition necessary in the primary sequence to have ACCD activity.

Amino Acid Sequence↗
PubMed2004

Vascular endothelial growth factor activation of sterol regulatory element binding protein: a potential role in angiogenesis.

By stimulating the migration and proliferation of endothelial cells (ECs), vascular endothelial growth factor (VEGF) is a potent angiogenic factor. However, the molecular mechanism involved in the VEGF-induced angiogenesis remains elusive. We hypothesized that sterol regulatory element binding proteins (SREBPs), transcription factors governing cellular lipid homeostasis, play an important role in regulating angiogenesis in response to VEGF. VEGF activated SREBP1 and SREBP2 in ECs, as demonstrated by the increased SREBPs, their cleavage products, and the upregulation of the targeted genes. VEGF-induced SREBP activation depended on SREBP cleavage-activating protein (SCAP), because knocking down SCAP by RNA interference (RNAi) inhibited SREBP activation in response to VEGF. SREBP activation was also blocked by 25-hydroxycholesterol (25-HC). To verify the functional implication of SREBPs in VEGF-induced angiogenesis, we tested the role of SREBPs in EC migration and proliferation. SCAP RNAi or 25-HC inhibited VEGF-induced pseudopodia extension and migration of ECs. Both treatments inhibited VEGF-induced EC proliferation, with cell growth arrested at the G(0)/G(1) phase and a concomitant decrease of the S phase. Blocking the PI3K-Akt pathway inhibited the VEGF-activated SREBPs, demonstrating that PI3K-Akt regulates SREBPs. Consistent with our in vitro data, SREBP1 was detected in newly developed microvasculatures in a rabbit skin partial-thickness wound-healing model. SREBP inhibition also markedly suppressed VEGF-induced angiogenesis in chick embryos. In summary, this study identifies SREBPs as the key molecules in regulating angiogenesis in response to VEGF.

Animals↗
PubMed2004

Crystallization and preliminary X-ray diffraction study of the catalytic subunit of archaeal H+ -transporting ATP synthase from Pyrococcus horikoshii OT3.

H+ -transporting ATP synthase (H+ -ATPase) is a multi-subunit complex which acts to produce ATP molecules. The catalytic subunit A of the archaeal-type H+ -ATPase from Pyrococcus horikoshii OT3 was cloned, expressed in Escherichia coli, purified and crystallized by the hanging-drop vapour-diffusion method with MPD as a precipitant. X-ray intensity data were collected to 2.55 A resolution at beamline BL41XU of SPring-8. The crystals belong to the tetragonal space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = b = 128.0, c = 104.7 A, and contain one molecule per asymmetric unit.

Catalytic Domain↗
PubMed2004

The role of post-radiation therapy FDG PET in prediction of necessity for post-radiation therapy neck dissection in locally advanced head-and-neck squamous cell carcinoma.

PURPOSE: The role of neck dissection after radiation therapy ([RT] with or without chemotherapy) for regionally advanced head and neck cancer is controversial. As much as 50% of residual lymphadenopathy after radiation has no viable tumor cells present on histopathologic analysis. [(18)F] fluorodeoxyglucose positron emission tomography (FDG PET) imaging can detect metabolically active cancer. This study examines the ability of post-RT FDG PET imaging to predict the tumor status of residual lymphadenopathy after nonsurgical management of regionally advanced neck disease. METHODS AND MATERIAL: From February 2000 to October 2002, 41 patients were treated definitively by radiation (with or without chemotherapy) and underwent FDG PET and computed tomography (CT) imaging after treatment to assess response. Patients with negative CT and FDG PET scans were observed and did not undergo neck dissection. Patients with radiographically persistent lymphadenopathy underwent either neck dissection or fine-needle aspiration of the lymph nodes using ultrasound guidance. The results of the FDG PET scans were correlated with the pathologic findings. RESULTS: Twelve patients with persistent lymphadenopathy underwent either neck dissection or fine-needle aspiration. Four of the 12 were found to have viable residual tumor in the cervical lymph nodes. The pathology did not correlate with the size of the lymph nodes in the pre-RT or post-RT CT studies. However, the pathology correlated strongly with the post-RT FDG PET studies. All patients with a negative post-RT FDG PET or those with a maximum standardized uptake value (SUV(max)) of less than 3.0 in the post-RT FDG PET were found to be free of residual viable tumor. Using an SUV(max) of less than 3.0 as the criterion for a negative FDG PET study, the negative predictive value was 100% and the positive predictive value was 80%. CONCLUSIONS: A negative post-RT FDG PET scan is very predictive of negative pathology in neck dissection or fine-needle aspiration even with large residual lymphadenopathy. Therefore, if the post-RT FDG PET scan is negative, neck dissection might not be required for regional control. A prospective study with longer follow-up and greater patient numbers is needed to determine whether a policy of deferring neck dissection based on a negative FDG PET is supported.

Adult↗
PubMed2004

Crystal structure of the regulatory subunit of archaeal initiation factor 2B (aIF2B) from hyperthermophilic archaeon Pyrococcus horikoshii OT3: a proposed structure of the regulatory subcomplex of eukaryotic IF2B.

Eukaryotic translation initiation factor 2B (eIF2B) is the guanine-nucleotide exchange factor for eukaryotic initiation factor 2 (eIF2). eIF2B is a heteropentameric protein composed of alpha- subunits. The alpha, beta, and delta subunits form a regulatory subcomplex, while the gamma and form a catalytic subcomplex. Archaea possess homologues of alpha, beta, and delta subunits of eIF2B. Here, we report the three-dimensional structure of an archaeal regulatory subunit (aIF2Balpha) from the hyperthermophilic archaeon Pyrococcus horikoshii OT3 determined by X-ray crystallography at 2.2A resolution. aIF2Balpha consists of two subdomains, an N-domain (residues 1-95) and a C-domain (residues 96-276), connected by a long alpha-helix (alpha5: 78-106). The N-domain contains a five helix bundle structure, while the C-domain folds into the alpha/beta structure, thus showing similarity to D-ribose-5-phosphate isomerase structure. The presence of two molecules in the crystallographic asymmetric unit and the gel filtration analysis suggest a dimeric structure of aIF2Balpha in solution, interacting with each other by C-domains. Furthermore, the crystallographic 3-fold symmetry generates a homohexameric structure of aIF2Balpha; the interaction is primarily mediated by the long alpha-helix at the N-domains. This structure suggests an architecture of the three subunits, alpha, beta, and delta, in the regulatory subcomplex within eIF2B.

Amino Acid Sequence↗
PubMed2004

Structure of macrophomate synthase.

Macrophomate synthase (MPS) is an enzyme that catalyzes an extraordinarily complex conversion reaction, including two decarboxylations, two carbon-carbon bond formations and a dehydration, to form the benzoate analogue macrophomate from a 2-pyrone derivative and oxalacetate. Of these reactions, the two carbon-carbon bond formations are especially noteworthy because previous experiments have indicated that they proceed via a Diels-Alder reaction, one of the most widely used reactions in organic synthesis. The structural evidence that MPS catalyzes an intermolecular Diels-Alder reaction has been reported recently [Ose et al. (2003), Nature (London), 422, 185-189]. Interestingly, the tertiary structure as well as the quaternary structure of MPS are similar to those of 2-dehydro-3-deoxygalactarate (DDG) aldolase, a carbon-carbon bond-forming enzyme that catalyzes the reversible reaction of aldol condensation/cleavage. Here, the structure of MPS is described in detail and compared with that of DDG aldolase. Both enzymes have a (beta/alpha)(8)-barrel fold and are classified as belonging to the enolase superfamily based on their reaction strategy. The basic principles for carbon-carbon bond formation used by both MPS and DDG aldolase are the same with regard to trapping the enolate substrate and inducing subsequent reaction. The major differences in the active sites between these two enzymes are the recognition mechanisms of the second substrates, 2-pyrone and DDG, respectively.

Aldehyde-Lyases↗
PubMed2004

[Coronary angiographic findings within 6 months after first myocardial infarction: a report of 878 cases].

OBJECTIVE: To investigate the characteristics of coronary lesions in patients after first myocardial infarction (MI). METHODS: From May 1998 to December 2000, coronary angiography was performed on 878 consecutive cases who had had first MI within 6 months and without history of previous coronary revascularization, 481 with anterior-lateral MI, 368 with inferior-posterior MI, 19 with posterio-lateral MI, and 10 with location-undetermined MI, and 394 receiving thrombolytic therapy 176 (44.7%) of which were treated successfully, and 525 (59.8%) with history of pre-infarction angina pectoris and 428 (48.7%) with history of post-infarction angina pectoris. RESULTS: (1) Normal coronary vessels or lesions less than 50% stenosis were seen only in 5.9% (52) of the patients. One-, two- and three-vessel diseases were present in 32.8% (288), 26.4% (232) and 34.9% (306) patients respectively. 3.2% (28) had concomitant left main stem (LMS) disease. Three-vessel coronary disease was significantly more common in the patients with a history of pre-infarction angina in comparison with those without such history (39.2% vs 28.3%, P < 0.01), and was significantly more common in the patients who did not undergo thrombolytic therapy in comparison with those who had received thrombolytic therapy (38.4% vs 30.5%, P < 0.05). (2) Only in 5.1% (41) cases the infarct-related artery (IRA) was normal or with lesions less than 50% stenosis. Total occlusion (100% stenosis), subtotal occlusion (95% to 99% stenosis), severe stenosis (70% to 94% stenosis) and borderline stenosis (50% to 69% stenosis) of IRA were seen in 29.6% (240), 22.6% (183), 37.9% (307) and 4.9% (40) of the cases respectively. Total occlusion of IRA occurred significantly less often in the thrombolytic group than in the non-thrombolytic group (24.6% vs 33.7%, P < 0.01). IRA could not be determined in 67 cases. (3) 90.5% (795), 79.4% (697), 57.2% (502) and 35.6% (313) of the patients had > or = 70% stenosis, > or = 90% stenosis, > or = 95% stenosis and total occlusion coronary lesions in at least one major coronary artery respectively, and coronary revascularization including PCI and CABG was needed on 84% (736/878) of the patients. CONCLUSION: Patients with a first MI usually have multi-vessel disease and severe coronary stenosis, with IRA having severe stenotic lesions. Revascularization treatment is needed in the majority of the patients. It is true too for the MI patients without history of pre- or post-infarction angina pectoris and those with successful thrombolytic therapy. Coronary angiography should routinely be performed on the patients who need further coronary revascularization.

Adult↗
PubMed2004

How oligomerization contributes to the thermostability of an archaeon protein. Protein L-isoaspartyl-O-methyltransferase from Sulfolobus tokodaii.

To study how oligomerization may contribute to the thermostability of archaeon proteins, we focused on a hexameric protein, protein L-isoaspartyl-O-methyltransferase from Sulfolobus tokodaii (StoPIMT). The crystal structure shows that StoPIMT has a distinctive hexameric structure composed of monomers consisting of two domains: an S-adenosylmethionine-dependent methyltransferase fold domain and a C-terminal alpha-helical domain. The hexameric structure includes three interfacial contact regions: major, minor, and coiled-coil. Several C-terminal deletion mutants were constructed and characterized. The hexameric structure and thermostability were retained when the C-terminal alpha-helical domain (Tyr(206)-Thr(231)) was deleted, suggesting that oligomerization via coiled-coil association using the C-terminal alpha-helical domains did not contribute critically to hexamerization or to the increased thermostability of the protein. Deletion of three additional residues located in the major contact region, Tyr(203)-Asp(204)-Asp(205), led to a significant decrease in hexamer stability and chemico/thermostability. Although replacement of Thr(146) and Asp(204), which form two hydrogen bonds in the interface in the major contact region, with Ala did not affect hexamer formation, these mutations led to a significant decrease in thermostability, suggesting that two residues in the major contact region make significant contributions to the increase in stability of the protein via hexamerization. These results suggest that cooperative hexamerization occurs via interactions of "hot spot" residues and that a couple of interfacial hot spot residues are responsible for enhancing thermostability via oligomerization.

Amino Acid Sequence↗
PubMed2004

Structure analysis of PH1161 protein, a transcriptional activator TenA homologue from the hyperthermophilic archaeon Pyrococcus horikoshii.

The crystal structure of the Bacillus subtilis TenA-homologue protein PH1161 from the hyperthermophilic archaebacterium Pyrococcus horikoshii was determined. TenA is known to belong to a new family of activators that stimulate the production of extracellular proteases in B. subtilis. A sequence-similarity search revealed that TenA-homologue proteins are widespread in bacteria and archaea, suggesting that this family of proteins plays an essential role in these organisms. In the present study, the first three-dimensional structure of a member of the TenA family of proteins was determined, unexpectedly revealing that the protein has a fold identical to that of haem oxygenase-1. Analysis has also shown that the protein has a unique ligand-binding pocket. Electron density of a bound ligand molecule was observed in this pocket. These results provide a valuable insight into the functional understanding of the TenA family of proteins.

Amino Acid Sequence↗