Polar interactions with aromatic side chains in alpha-helical peptides: Ch...O H-bonding and cation-pi interactions.
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Biomedical subjects
Publications and source records attributed to Z Shi.
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The electrochemical behavior of a film of single-wall carbon nanotubes (SWNTs) functionalized with carboxylic acid groups was studied extensively on a glassy carbon (GC) electrode. One stable couple corresponding to the redox of the carboxylic acid group, which was supported by XPS and IR experiments, was observed. The electrode process involved four electrons, while the rate-determining step was a one-electron reduction. The SWNT film-modified electrode showed favorable electrocatalytic behavior toward the oxidation of biomolecules such as dopamine, epinephrine, and ascorbic acid.
The mechanisms of resistance to nucleoside analogues established in preclinical models are rarely found in primary tumors resistant to therapy with these agents. We tested the hypothesis that cells sense sublethal incorporation of analogues into DNA during replication and react by arresting further DNA synthesis and cell cycle progression. After removal of drug, cells may be able to repair damaged DNA and continue proliferation, thus escaping nucleoside analogue toxicity. As a corollary, we evaluated whether dysregulation of this mechanism causes cell death. Using gemcitabine as a model of S-phase-specific nucleoside analogues in human acute myelogenous leukemia ML-1 cells, we found that DNA synthesis decreased, cells arrested in S-phase transit, and 60-70% of the population accumulated in S-phase in response to cytostatic conditions. Proliferation continued after washing the cells into drug-free medium. S-phase-arrested cells were then treated with otherwise nontoxic concentrations of UCN-01, which caused rapid onset of apoptosis without cell cycle progression specifically in cells with an S-phase DNA content. Thus, S-phase arrest by nucleoside analogues sensitizes cells to UCN-01, which appears to activate signaling for death mechanisms and/or inhibit survival pathways. These results differ from those in cells arrested at the G2 checkpoint, in which UCN-01 abrogates cell cycle arrest, permitting cells to progress in the cell cycle before apoptosis.
A new compound, Al2P2O8F2.[(CH3)2CHNH2CH2CH2NH2CH(CH3)2] (denoted AlPO-CJ8), with a 1-dimensional fluoroaluminophosphate chain and an Al/P ratio of unity has been synthesized solvothermally by using isopropylamine as an organic additive. It is characterized by X-ray powder diffraction (XRD), inductively coupled plasma (ICP), ion selective electrodes (ISE), and TGA-DTA analyses and structurally determined by single-crystal X-ray diffraction analysis. AlPO-CJ8 crystallizes in the triclinic space group P1 with a = 5.0306(8) A, b = 9.3626(15) A, c = 10.6131(17) A, alpha = 65.949(4) degrees, beta = 88.218(4) degrees, gamma = 77.19 degrees, and Z = 2. Its structure is built up by alternation of tetrahedral PO3(=O) and AlO3F units to form infinite 1-D Al2P2O8F2(2-) macroanionic chains. The inorganic chains are held together by diprotonated N,N'-diisopropylethylenediamine through H-bonds. The organic species N,N'-diisopropylethylenediamine is believed to be formed through solvothermal reaction of the organic additive isopropylamine and the solvent ethylene glycol. The existence of terminal P=O and Al-F bond groups in the 1-D chain indicates that it has potential to further set up higher dimensional networks through condensations.
It is generally understood that helical proteins are stabilized by a combination of hydrophobic and packing interactions, together with H-bonds and electrostatic interactions. Here we show that polar side-chain interactions on the surface can play an important role in helix formation and stability. We review studies on model helical peptides that reveal the effect of weak interactions between side chains on helix stability, focusing on some nonclassical side-chain-side-chain interactions: complex salt bridges, cation-pi, and C-H em leader O H-bonding interactions. Each of these can be shown to contribute to helix stability, and thus must be included in a comprehensive catalogue of helix stabilizing effects. The issue of the structure of the unfolded states of helical peptides is also discussed, in the light of recent experiments showing that these contain substantial amounts of polyproline II conformation.
The effectiveness of vaccination programs would be enhanced greatly through the availability of vaccines that can be administered simply and, preferably, painlessly without the need for timed booster injections. Tetanus is a prime example of a disease that is readily preventable by vaccination but remains a major threat to public health due to the problems associated with administration of the present vaccine. Here we show that a protective immune response against live Clostridium tetani infection in mice can be elicited by an adenovirus vector encoding the tetanus toxin C fragment when administered as a nasal or epicutaneous vaccine. The results suggest that these vaccination modalities would be effective needle-free alternatives. This is the first demonstration that absorption of a small number of vectored vaccines into the skin following topical application of a patch can provide protection against live bacteria in a disease setting.
In cell culture systems insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) can both enhance and inhibit IGF-I action. To investigate the biological role of IGFBP-3 in vivo, transgenic (Tg) mice that constitutively overexpress the human IGFBP-3 complementary DNA (cDNA) driven by the mouse phosphoglycerate kinase I (PGK) and the cytomegalovirus (CMV) promoters were examined. Serum levels of human IGFBP-3 in CMVBP-3 and PGKBP-3 Tg mice were 4.7 and 5.8 microgram/ml, respectively and total IGFBP-3 was increased 4.9- and 7.7-fold compared with that in wild-type (Wt) mice. In PGKBP-3 Tg mice the levels of transgene expression were similar in all tissues. Although CMVBP-3 mice demonstrated similar levels of expression of the transgene as PGKBP-3 mice in most tissues, markedly elevated expression was apparent in the kidney and heart. The transgene-derived IGFBP-3 circulated as a 150-kDa ternary complex, and serum IGF-I levels were elevated 1.9- to 2.8-fold in Tg mice compared with Wt mice. A significant reduction in birth weight of approximately 10% and a modest reduction in litter size were apparent in both Tg strains. Early postnatal growth, as assessed by both body weight and length, was significantly reduced in Tg mice compared with Wt mice. This was more marked in PGKBP-3 than in CMVBP-3 mice, who demonstrated a propensity to adiposity after weaning. The relative organ weights of brain and kidney were reduced in both Tg strains, whereas liver size and epididymal fat were significantly increased in CMVBP-3, but not PGKBP-3, mice. Our data indicate that overexpression of IGFBP-3 is associated with modest intrauterine and postnatal growth retardation despite elevated circulating IGF-I levels.
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OBJECTIVE: To investigate the mechanism of discogenic groin pain. METHODS: Twenty-one adult wistar rats were divided into experimental group (paravertebral sympathetic trunks were reserved), control group (paravertebral sympathetic trunks were resected) and self-control group (right paravertebral sympathetic trunks were resected, the left ones were reserved) randomly. Each group has 7 rats. Horseradish peroxidase (HRP) were injected into the L5-L6 intervertebral discs from right postero-lateral side. Bilateral L1, L2 spinal ganglia were sectioned after 48 hours to observe the HRP labeled cells and the effect of resection of paravertebral sympathetic trunks. Another 7 adult wistar rats were used. The same steps of injection, removal and section as in experimental group were taken. Combining method of HRP retrograde tracer with immunocytochemistry stained the sections to determine the nature of HRP labeled cells. RESULTS: HRP labeled cells were found in bilateral L1, L2 spinal ganglia in each group. The comparison results of labeled cells numbers between groups (experimental group from 22.5 +/- 7.1 to 29.3 +/- 9.7, control group from 12.9 +/- 5.1 to 13.3 +/- 4.9, P < 0.01) and of self-control group (left 24.8 +/- 6.7, 30.6 +/- 8.4, right 15.8 +/- 4.4, 14.5 +/- 4.1, P < 0.01) show that the numbers of HRP labeled cells were significantly less than that after resection of paravertebral sympathetic trunks. HRP and SP double-labeled cells can be recognized in bilateral L1, L2 spinal ganglia in immunocytochemistry experiment. CONCLUSIONS: Discogenic groin pain is referred pain which is transmitted by sympathetic nerves and appears in the area that was segmentally innervated by anterior rami of L1 and L, spinal nerves.
OBJECTIVE: To research the direct electrophysiological evidence of discomplete spinal cord injury (SCI) and the effect of 4-aminopyridine on it. METHODS: Motor evoked potentials (MEPs), both spinal cord recorded MEPs (scMEPs) and extracellularly recorded MEPs (exMEPs) were recorded and characterized on a T13 epidural electrode (scMEPs) and an extracellular microelectrode (exMEPs) for 10 normal rats and 40 rats with lesions of various severity (sham, 35 g.cm force (gcf), 70 gcf, 100 gcf impact injury) at the T8-T9 cord using the Allen's drop model. The incline plane and Tarlov techniques were used to assess clinical neurological function. RESULTS: MEPs in the normal rats were elicited by applying transcortical suprathreshold stimulation consisting of 3-4 early negative peaks (N1, N2, N3 and N4) followed by several late waves. The N1 and N2 peaks were largest in the anterior and ventrolateral funiculus, respectively, which was indicative of extrapyramidal pathways. The 100 gcf impact injuries and the cord transection abolished the MEP distal to the lesion, whereas the 35 gcf injuries resulted in a latency shift and amplitude decrement of the MEP peaks. Eighteen of the 20 rats with 70 gcf-injuries showed clinical paraplegia. Among them, 7 rats had neurophysiological evidence of residual conduction pathways through the lesioned cord segment, such as the presence of N1 and N2 peaks in the scMEPs or exMEPs. After 4-aminopyridine (4-AP) administrations (1 mg/kg), the amplitude of the spared exMEP increased significantly and spread more widely. CONCLUSIONS: MEPs evoked by transcortical stimulation travel mostly in the extrapyramidal tract. MEP monitoring could provide an excellent method of detecting the functional integrity of the motor tracts after SCI, and could even detect spared motor fibers after discomplete SCI. Furthermore, the use of 4-AP or other K+ channel blocking agents may be a potential treatment for patients with chronic moderate to severe SCI.
The ichneumonid Diadromus collaris (Gravenhorst) has been recorded in many parts of the world as an important parasitoid of the diamondback moth, Plutella xylostella (Linnaeus), a serious pest of brassica vegetable crops worldwide. Some aspects of its biology and its interactions with Oomyzus sokolowskii (Kurdjumov), another major parasitoid of the same pest, were studied in the laboratory. At 25 degrees C, female wasps did not have mature eggs in their ovaries until about 12 h after emergence. Both males and females mated successfully 24-48 h after emergence, and females started to oviposit one to two days after emergence. Unmated females produced male progeny only; mated females produced progeny of both sexes. The development rate of the parasitoid increased linearly with temperature from 15 to 30 degrees C, with an estimated low temperature threshold of 7.4 degrees C and a thermal constant of 225.1 day-degrees for development from egg to adulthood. Rates of survival from larva to adulthood were about 90% between 20 and 28 degrees C and decreased as temperature decreased or increased. No immatures survived to adulthood at 35 degrees C. When provided with honey solution, the females lived on average 8.3, 11.5 and 7.0 days, and parasitized 26, 44 and 46 host pupae at 20, 25 and 30 degrees C, respectively. Female wasps could be stored at 15 degrees C for up to four weeks without detrimental effects on reproduction. Females of D. collaris attacked host pupae already parasitized by O. sokolowskii, inserting their ovipositor into the hosts at a similar frequency as into unparasitized host pupae, but they did not lay eggs inside the hosts.
OBJECTIVE: To explore the role of tentorium cerebelli hiatus incision in treating severe and most severe brain injuries complicated by tentorial herniation. METHODS: From July 1994 to July 1999 tentorium cerebelli hiatus incision was done based on intracranial hematoma evacuation and bone flap craniectomy decompression in 70 cases of severe and most severe brain injuries complicated by tentorial herniation. RESULTS: Of the 70 cases, GCS 3-5 was in 23 and GCS 6-8 in 47; satisfactory recovery in 39 cases (55.7%), moderate disability in 12 (17.1%), severe deficit in 6 (8.6%), vegetative survival in 4 (5.7%) and 8 (11.4%) died. CONCLUSIONS: Tentoriun cerebelli incision is helpful in alleviating secondary brain stem injury from tentorial herniation and in reducing the disability and death rate of the patients.
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OBJECTIVE: To study the therapeutic effects of transcatheter arterial chemoembolization (TACE) combined with beta-ultrasound guided percutaneous ethanol injection (PEI) at multiple points for hepatocellular carcinoma. METHODS: Eighty-seven patients with hepatocellular carcinoma were divided into two groups: Group A, 45 patients were treated with TACE only, group B, 42 patients were treated with TACE plus PEI. RESULTS: In group A patients, the 1-, 2-, and 3-year survival rates were 66.7%, 41.4%, and 21.4%, respectively. Only 26.1% of cancer specimens showed complete necrosis by pathologic examination in group A. In group B, the 1-, 2-, and 3-year survival rates were 97.1%, 85.71% and 65.71%, respectively, with complete necrosis in 81.8%. CONCLUSION: The therapeutic effects of transcatheter arterial chemoembolization combined with percutaneous multiple point ethanol injection through liver puncture is much better than that of TACE alone.
To prevent post-transfusion toxoplasmosis, the sera of blood donors, per six of which were mixed as a pool, were examined for anti-Toxoplasma gondii antibiodies by Dot-immunogold silver staining (Dot-IGSS) with the single serum specimens examined simultaneously. The results showed that the sensitivity and specificity of serum pool method were 92.31% and 99.96% respectively. The consistent rate between the two methods was 99.73% and kappa value was 0.947 (p<0.01). Considering the mean infection rate of Toxoplasma gondii being 4.86% in China, if the serum pool method be adoped, with pool size k=5, a 57% reduction in the number of tests, as well as the cost of the screen, can be expected. Beside the social benefit, consequent upon the interruption of the Toxoplasma gondii infection spread through blood transfusion also can be expected.
OBJECTIVE: To define the relevance of VEGF status to the prognosis of breast cancer. METHODS: The tissues of 70 invasive ductal breast carcinomas were evaluated for VEGF protein expression by immunohistochemistry LSAB method, and the prognostic value of VEGF status was assessed in combination with the follow-up data on those breast cancer patients. RESULTS: VEGF status was inversely correlated with relapse-free survival and overall survival. Kaplan-Merier survival curve showed that VEGF-rich tumor group had higher relapse rate and mortality rate. Multivariate regression analysis confirmed that the VEGF status had certain prognostic value, but it could not be considered as an independent prognostic indicator. CONCLUSION: VEGF status is one of the significant prognostic indicators of breast cancer.
Mutations in the EXT1 gene are responsible for human hereditary multiple exostosis type 1. The Drosophila EXT1 homologue, tout-velu, regulates Hedgehog diffusion and signaling, which play an important role in tissue patterning during both invertebrate and vertebrate development. The EXT1 protein is also required for the biosynthesis of heparan sulfate glycosaminoglycans that bind Hedgehog. In this study, we generated EXT1-deficient mice by gene targeting. EXT1 homozygous mutants fail to gastrulate and generally lack organized mesoderm and extraembryonic tissues, resulting in smaller embryos compared to normal littermates. RT-PCR analysis of markers for visceral endoderm and mesoderm development indicates the delayed and abnormal development of both of these tissues. Immunohistochemical staining revealed a visceral endoderm pattern of Indian hedgehog (Ihh) in wild-type E6.5 embryos. However, in both EXT1-deficient embryos and wild-type embryos treated with heparitinase I, Ihh failed to associate with the cells. The effect of the EXT1 deletion on heparan sulfate formation was tested by HPLC and cellular glycosyltransferase activity assays. Heparan sulfate synthesis was abolished in EXT1 -/- ES cells and decreased to less than 50% in +/- cell lines. These results indicate that EXT1 is essential for both gastrulation and heparan sulfate biosynthesis in early embryonic development.
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