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Biomedical subjects

K Xu

Publications and source records attributed to K Xu.

At least 109 records · Page 6Linked to original sources

Vascular endothelial growth factor upregulation in transient global ischemia induced by cardiac arrest and resuscitation in rat brain.

This study examined vascular endothelial growth factor (VEGF) expression in rat brain after reversible global cerebral ischemia produced by cardiac arrest and resuscitation. Three alternative splicing forms, VEGF(188), VEGF(164) and VEGF(120), were observed in cortex, hippocampus and brainstem by RT-PCR analysis. After 24 h of recovery from cardiac arrest, mRNA levels corresponding to VEGF(188) and VEGF(164) were significantly increased by about double in all the regions analyzed. These mRNA levels remained elevated at 24 and 48 h of recovery but returned to basal expression after 7 days of recovery. Changes in VEGF(120) expression after cardiac arrest did not reach statistical significance. VEGF protein expression measured by Western blot was also increased by about double at 24 and 48 h of recovery but returned to control levels after 7 days of recovery. VEGF immunohistochemistry localized this increased expression mostly associated with astrocytes. Considering its biological activity, VEGF induction after cardiac arrest and resuscitation may be responsible for the increased vascular permeability and the resultant vasogenic edema, found 24-48 h after reversible global ischemia.

Animals↗

[The therapeutic effect of Chinese medicinal herbs on HIV patients].

OBJECTIVE: To study the therapeutic effect of Chinese medicinal herbs on HIV patients. METHODS: We adopted the combined Chinese medicinal herbs for treatment, its chief component is to enhance human immunity and the complementary part is suited for lightening the clinical synptoms. The clinical aspects, the CD4, CD8 lymphocyte numbers and the plasma viral load of the patients were compared before and after the treatment. RESULTS: Of 28 patients exemined, they all had different degrees of body weight increasing, averagely increased 5.4 kg after treatment. 7 cases having a long-time fever, 4 cases of diarrhea, 2 cases of large scale skin ulcer and 1 case of skin rash all had their synptoms disappeared ofter one month treatment. 10 cases, who had lymph nodes enlargement, after treated five months with Chinese medicinal herbs, 3 of them the swelling lymph nodes disappeared, 7 of them the lymph nodes diminished or decreased in number. CD4 lymphocytes increased in 42.9% and 50.0% patients and viral load decreased in 71.4% and 80.0% patients after two months and five months treatment with Chinese medicinal herbs respectively. Taking clinical symptoms and laboratory indexs into consideration, the total effective rate of Chinese medicinal herbs reached 94.0%. CONCLUSION: The Chinese medicinal herbs can obviously improve the clinical symptoms, increase CD4 lymphocytes and decrease serum viral load of the HIV patients, thus provides evidence that the Chinese medicinal herbs can be used for control of HIV infection and treatment of AIDS patients.

Adjuvants, Immunologic↗

The structural characteristics and mechanical behaviors of nonstoichiometric apatite coatings sintered in air atmosphere.

Two types of nonstoichiometric apatite coatings on Ti6Al4V substrates were prepared in our laboratory by electrodeposition and hydrothermal synthesis. One was composed of highly pure needle-like calcium-deficient hydroxyapatite, and the other consisted of needle-like calcium-deficient hydroxyapatite and plate-like brushite. In this paper, the morphology, phase transition, and bonding strength of these coatings sintered at 450( degrees ) approximately 980 degrees C in an air atmosphere were studied. In addition, the residual stresses in pure calcium-deficient hydroxyapatite coatings and coatings sintered at 800 degrees C were measured by a hole-drilling method. The results show that after being sintered at a higher temperature, the coating/Ti6Al4V samples exhibited structural characteristics such as biphasic [hydroxyapatite + beta-Ca3(PO4)2] coatings and dense TiO2 film/Ti6Al4V in which the residual stresses in the coatings slightly increased. In addition, the results indicate that bonding strength was improved.

Air↗

First unaffected pregnancy using preimplantation genetic diagnosis for sickle cell anemia.

CONTEXT: Sickle cell anemia is a common autosomal recessive disorder. However, preimplantation genetic diagnosis (PGD) for this severe genetic disorder previously has not been successful. OBJECTIVE: To achieve pregnancy with an unaffected embryo using in vitro fertilization (IVF) and PGD. DESIGN: Laboratory analysis of DNA from single cells obtained by biopsy from embryos in 2 IVF attempts, 1 in 1996 and 1 in 1997, to determine the genetic status of each embryo before intrauterine transfer. SETTING: University hospital in a large metropolitan area. PATIENTS: A couple, both carriers of the recessive mutation for sickle cell disease. INTERVENTIONS: Standard IVF treatment, intracytoplasmic sperm injection, embryo biopsy, single-cell polymerase chain reaction and DNA analyses, embryo transfer to uterus, pregnancy confirmation, and prenatal diagnosis by amniocentesis at 16.5 weeks' gestation. MAIN OUTCOME MEASURE: DNA analysis of single blastomeres indicating whether embryos carried the sickle cell mutation, allowing only unaffected or carrier embryos to be transferred. RESULTS: The first IVF attempt failed to produce a pregnancy. Of the 7 embryos analyzed in the second attempt, PGD indicated that 4 were normal and 2 were carriers; diagnosis was not possible in 1. Three embryos were transferred to the uterus on the fourth day after oocyte retrieval. A twin pregnancy was confirmed by ultrasonography, and subsequent amniocentesis revealed that both fetuses were unaffected and were not carriers of the sickle cell mutation. The patient delivered healthy twins at 39 weeks' gestation. CONCLUSION: This first unaffected pregnancy resulting from PGD for sickle cell anemia demonstrates that the technique can be a powerful diagnostic tool for carrier couples who desire a healthy child but wish to avoid the difficult decision of whether to abort an affected fetus.

Adult↗

A new scorpion toxin (BmK-PL) stimulates Ca2+-release channel activity of the skeletal-muscle ryanodine receptor by an indirect mechanism.

A peptide toxin isolated from the Chinese scorpion Buthus martensi Karsch (BmK-PL) stimulated Ca2+-release channel activity in both triad membranes and reconstituted ryanodine receptors partially purified from rabbit skeletal muscle. In [3H]ryanodine binding experiments, the toxin increased the affinity of ryanodine for the receptor, from a Kd of 24.3 nM to 2.9 nM, which is an enhancement similar to that seen with known receptor activators, such as ATP and high concentrations of KCl. In contrast, toxin enhancement was not observed with purified receptors, although intrinsic binding activity and stimulation by the conventional receptor activators were retained. In single channel recordings of Ca2+-release activity, the toxin increased the open channel probability (Po) from 0.019 to 0.043 (226% of control) in triad preparations. Further toxin enhancement of Po from 0.07 to 0.37 (529% of control) was observed using partially-purified receptors in the presence of ATP. When purified receptors were assayed in the presence of ATP, however, they showed a high value of Po (0.33) and no further increase was observed following application of the toxin. Results derived from two different experimental methods consistently suggest that a molecule(s) required for toxin-induced enhancement is absent from the purified receptor preparation. Western blot analysis of receptors prepared using three different protocols showed that triadin was missing from the purified receptor preparation. The scorpion toxin minimally enhanced Ca2+-release channel activity of cardiac preparations. From these results, we conclude that the toxin preferentially increases the activity of skeletal-muscle ryanodine receptors by an indirect mechanism, possibly binding to associated protein molecule(s). Triadin is a strong candidate for such a molecule.

Amino Acid Sequence↗

Cerebral metabolic profile, selective neuron loss, and survival of acute and chronic hyperglycemic rats following cardiac arrest and resuscitation.

Cortical metabolites and regional cerebral intracellular pH (pHi) were measured in normoglycemic (NM), acute hyperglycemic (AH), and chronic hyperglycemic (CH, 2 week duration, streptozotocin-induced) Wistar rat brains during cardiac arrest and resuscitation. During total ischemia in AH and CH rats (plasma glucose approximately 30 mM), cortical ATP, PCr, glucose, and glycogen all fell significantly as expected. Lactate levels increased dramatically in association with a concomitant intracellular acidosis. Although lactate reached higher concentrations in AH and CH than NM, pHi was significantly lower only in the AH group. With 5 min of reperfusion, all groups recovered to near baseline in all variables, though lactate remained elevated. In a separate aspect of the study, animals from each experimental group were allowed to recover for 4 days following resuscitation, with outcome being gauged by mortality rate and hippocampal CA1 neuron counts. NM survival rate was significantly better than AH and CH. In particular, no CH rats survived for 4 days despite rapid initial recovery. After 4 days, the AH group had suffered significantly greater CA1 neuron loss than the NM rats. In summary, our research identified differences in intra-ischemic acid-base status in the two hyperglycemic groups, suggesting that chronic hyperglycemia may alter the brain's buffering capacity. These observations may account for differences between acutely and chronically hyperglycemic subjects regarding outcome, and they suggest that factors other than hydrogen ion production during ischemia are responsible for modulating outcome.

Acidosis, Lactic↗

Glial fibrillary acidic protein is necessary for mature astrocytes to react to beta-amyloid.

Upregulation of the glial fibrillary acidic protein (GFAP) in astrocytes is a hallmark of the phenomenon known as reactive gliosis and, yet, the function of GFAP in this process is largely unknown. Our previous studies have shown that mature astrocytes react vigorously to substrate bound beta-amyloid protein (BAP) in a variety of ways (i.e., increased GFAP, enhanced motility, unusual aggregation patterns, inhibitory ECM production). In order to uncover which, if any, of these phenomena are causally related to the function of GFAP, primary cortical astrocytes from transgenic mice lacking GFAP were cultured on BAP substrates at low or high density and at various lengths of time following in vitro maturation. Differences between mutant and control cells became progressively more obvious when cells were matured in vitro for two weeks or longer and especially in cultures that were at high density. Mature control astrocytes show a dramatic response to BAP by aggregating into a meshwork of rope-like structures that completely bridge over the peptide surface. In marked contrast, mature GFAP-null astrocytes initiate the response much more slowly and had a much reduced ability to aggregate tightly. Furthermore, we prepared hippocampal slice cultures from GFAP-/- and GFAP+/+ mice and compared their astrocytic responses to injected BAP. GFAP-/- astrocytes of hippocampal slice cultures failed to form a barrier-like structure around the edge of the BAP deposit as did GFAP+/+ astrocytes. Our data suggest that GFAP may be essential for mature astrocytes to constrain certain types of highly inflammatory lesions in the brain.

Amyloid beta-Peptides↗

[Identification of mutations in the phenylalanine hydroxylase gene and exon 5 novel mutation Y166X(C-->G) in Yunnan].

OBJECTIVE: To identify the mutations of the phenylalanine hydroxylase gene in Yunnan so as to enhance the gene diagnosis of classical phenylketonuria (PKU) in that south-western province of China. METHODS: Exons 4,5,6,7,10,11 and 12 of the phenylalanine hydroxylase(PAH) were analyzed in 13/14 children affected with classical PKU from Yunnan by using PCR-single strand conformation polymorphism (PCR-SSCP),PCR-ASO dot blot hybridization,allele specific polymerase chain reaction(ASPCR) and PCR-direct sequencing. RESULTS: Five missense mutations, i.e. R243Q. (5/26), Y204C(3/28), G247V(1/26),R413P(2/28) and T418P(1/28);three nonsense mutations,i.e. Y166X(C-->G)(2/26),W326X(1/28) and Y356X(2/26);and one silent mutation(V399V)(2/26) were identified. The nonsense mutation Y166X(C-->G) should be a novel mutation as compared with the PAH Mutation Database. CONCLUSION: Five kinds of popular PAH gene mutation (R243Q,Y204C,V399V,Y356X and R413P) identified in the people of Yunnan are similar to those in the northern people, but such characteristic is different from that in the southern people. This finding will enhance the efficacy in gene diagnosis of PKU and will be of reference value for studies of population and regional difference in the pattern of PAH mutation distribution.

Child↗

Selective induction of protective MHC class I-restricted CTL in the intestinal lamina propria of rhesus monkeys by transient SIV infection of the colonic mucosa.

The identification of mucosal immune responses required for protection against sexual transmission of HIV is essential for the development of an efficacious vaccine. To gain a better understanding of these responses, we have characterized the immune responses in the lamina propria (LP) and epithelium of the jejunum, the mesenteric lymph nodes, and peripheral blood (PBMC) of 11 rhesus monkeys following colonic exposure to two molecular clones of SIV. Two monkeys had no signs of infection. Three monkeys became persistently infected. Transient infections, characterized by the sporadic detection of virus in the periphery and/or detection of SIV-specific immune responses in either the gut-associated tissues or PBMC, were induced in six of the monkeys. One persistently infected and three transiently infected monkeys had high levels of SIV env-specific MHC class I restricted CTL in the jejunal LP. Another transiently infected monkey had SIV-specific IgA secreting B cells in the LP. Three or six months postexposure, these animals and four naive controls were challenged intracolonically with the heterologous primary isolate, SIV/DeltaB670. All four monkeys with strong SIV env-specific MHC-restricted CTL in the LP were protected, whereas none of the naive controls or the remaining seven monkeys with little or no CTL in the LP were protected. These experiments provide the first direct evidence that transient mucosal infection can induce SIV-specific immunity that remains localized to the gut-associated tissues. Furthermore, a strong correlation between SIV env-specific MHC-restricted CTL in the LP and protection against colonic mucosal challenge was observed.

Animals↗

Quantitative analysis of cimetidine in human plasma using LC/APCI/SRM/MS.

A quantitative method was developed and validated for rapid and sensitive analysis of cimetidine in human plasma. The method involved the use of liquid chromatography (LC) coupled with atmospheric pressure chemical ionization (APCI) and selected reaction monitoring (SRM) mass spectrometry (MS). A cimetidine analog, SKF92374, was used as the internal standard. Separation of cimetidine and the internal standard was accomplished using a reverse-phase HPLC column (C18). The eluted components were ionized by the APCI source and subsequently detected by a highly selective triple quadrupole mass spectrometer in the SRM mode. Linear standard curves were obtained from 5 ng/mL (lower limit of quantitation) to 10,000 ng/mL. The results demonstrated excellent precision (%RSD 1. 1-8.9%) and accuracy (94.7-108.0%) over this range. In addition, the amount of plasma sample needed for analysis was small (50 muL), and the plasma pretreatment (analyte recovery >94%) was simple and time saving. This assay was used to evaluate cimetidine levels in premature infants following intravenous infusion of cimetidine.

Child↗

S100A8: emerging functions and regulation.

The functional importance of members of the S100 Ca2+-binding protein family is becoming apparent. Murine (m)S100A8 (initially named CP-10) is a potent chemoattractant (10(-13) to 10(-11) M) for myeloid cells and the chemotactic activity of other S100s has since been reported, suggesting a new class of chemoattractants. Murine S100A8 has been associated with a number of acute and chronic inflammatory conditions including bacterial infection, atherogenesis, and cystic fibrosis. It is expressed constitutively with S100A9 in neutrophils and is regulated by inflammatory stimulants in macrophages and microvascular endothelial cells. The lack of co-expression of S100A9 with S100A8 in activated macrophages suggests distinct functions for the proteins expressed by different cell types. Glucocorticoids up-regulate induction of mS100A8 by inflammatory mediators, and its exquisite sensitivity to oxidation suggests that it may protect against oxidative tissue damage. Inactivation of the mS100A8 gene is embryonic lethal, providing the first evidence for non-redundant function of a member of the S100 gene family. S100A8 may have an immunoregulatory role by contributing to the regulation of fetal-maternal interactions. It may play a protective role and its absence may allow infiltration by maternal cells, a process eventually manifesting as resorption. This review focuses on the variety of emerging functions attributed to murine S100A8, a protein implicated in embryogenesis, growth, differentiation, and immune and inflammatory processes.

Animals↗

Alterations in nigrostriatal dopaminergic function within BDNF mutant mice.

The influence of brain-derived neurotrophic factor (BDNF) upon the nigrostriatal dopaminergic system was evaluated in weanling and adult mice carrying a targeted inactivated BDNF gene. Regional specificity of this BDNF mutation was assessed by assaying catecholamine concentrations within the corpus striatum, hypothalamus, and olfactory bulbs. In weanling mice dopamine, but not norepinephrine, concentrations within the corpus striatum of homozygous mutant (-/-) mice were significantly reduced with levels being 54% that of the wild-type controls (+/+) and 49% that of the heterozygous mutant (+/-) mice. While no differences were obtained among the three genotypes for hypothalamic dopamine, norepinephrine concentrations of -/- mice were significantly lower, being 62% of +/+ mice and 49% of +/- mice. The dopamine concentrations of -/- mice within the olfactory bulb were significantly reduced (69%) compared to the +/-, but not +/+ mice. Olfactory bulb norepinephrine concentrations showed a statistically significant difference among each of the three conditions with minimal levels in -/- mice (62% of +/+ and 45% of +/-). In the adults, catecholamine concentrations were measured only in +/+ and +/- mice since -/- mice do not typically survive past 21 days. Dopamine, but not norepinephrine, concentrations within the corpus striatum were significantly increased (116%) in +/- compared to +/+ mice. No other statistically significant differences were obtained in catecholamine concentrations within the hypothalamus or olfactory bulb in these adult mice. These results show that homozygous BDNF mutations produce severe depletions within the nigrostriatal dopaminergic system and substantial reductions of norepinephrine within the hypothalamus and olfactory bulb. Interestingly, maximal catecholamine concentrations for all areas sampled at both ages were observed in the +/- mice. These latter findings may indicate some subtle changes in catecholamine functions resulting from a heterozygous BDNF mutation.

Animals↗

Gene cloning and sequencing of BmK AS and BmK AS-1, two novel neurotoxins from the scorpion Buthus martensi Karsch.

Based on the known amino acid sequences of BmK AS and BmK AS-1, the gene specific primers were designed and synthesized for 3' and 5' RACE (Rapid Amplification of cDNA Ends). Their partial cDNA fragments obtained by 3' and 5' RACE were cloned and sequenced, and the full length cDNA sequences of BmK AS and BmK AS-1 were then completed by overlapping their two partial cDNA sequences, respectively. The predicted amino acid sequences both consist of 85 amino acid residues including a putative signal peptide of 19 residues and a mature toxin of 66 residues. They are different in 17 amino acid residues, among them 11 residues in the mature toxin. The predicted amino acid sequences of BmK AS and BmK AS-1 were almost consistent with those determined and revised (personal communication), only different in one and two residues at their COO-terminal parts, respectively. Based on the determined cDNA sequences, and using the total DNAs isolated from the scorpion venom glands as a template, the genomic DNAs of BmK AS and BmK AS-1 were also amplified by PCR and sequenced. It showed that no intron was inserted in their open reading frames, while in the exon of signal peptide sequences of other Na+, K+ and Cl- channel toxins from the same scorpion, an intron is usually found. However, the Northern blot hybridization results indicated that the sizes of their mRNA should be around 800 bp. Their extra sequences around 400 bp which might function as an intron should be located at their 5' untranslated regions.

3' Untranslated Regions↗

Fracture toughness (KIc) of a dental porcelain determined by fractographic analysis.

OBJECTIVES: Fractographic analysis of indentation cracks is performed following flexure testing as part of the ASTM (1999) standard for fracture toughness, KIc, determination in advanced ceramics. This method depends on the conduciveness of the material towards fractographic interpretation. The purpose of this study was to evaluate the use of fractography in fracture toughness methods with a feldspathic dental porcelain, in which KIc was measured fractographically as well as numerically using two controlled-flaw beam bending techniques. METHODS: The following methods for KIc determination were applied to a dental porcelain containing a leucite volume fraction of 15-20%: (1) surface crack in flexure (SCF) (dependent upon fractographic analysis); and (2) indentation strength (IS) at indentation loads of 9.8 and 19.6 N (applying both standard numeric calculations and fractographic analysis). The testing environments were (1) ambient air (IS and SCF) and (2) flowing dry nitrogen (SCF). RESULTS: No significant differences were found between numeric and fractographic KIc values for the IS technique at both indentation loads (9.8 and 19.6 N) in ambient air, although KIc values were sensitive to indentation load. Due to the presence of residual stresses, stable crack extension was observed fractographically in all IS specimens, as evidenced by differences between initial (ainitial) and critical (acritical) crack dimensions. For the SCF method, there was a significant difference in toughness between specimens tested in air versus dry nitrogen, however no fractographic evidence for chemically assisted slow crack growth (SCG) was observed. SIGNIFICANCE: The SCF method as described by the ASTM standard was applicable to the feldspathic porcelain and produced very comparable results with the numeric toughness calculations of the IS procedure. However, fractographic analysis of the surface crack was somewhat difficult for this glassy ceramic compared with polycrystalline ceramics. Knowledge about stable crack extension or slow crack growth and its fractographic appearance is essential when estimating the toughness from examination of flaw dimensions on fractured surfaces since large calculation errors may occur if these effects are not taken into account.

Aluminum Silicates↗

Covalent modifications to 2'-deoxyguanosine by 4-oxo-2-nonenal, a novel product of lipid peroxidation.

Two major products (adducts A and B) from the reaction of 2-deoxyguanosine (dGuo) with 13-hydroperoxylinoleic acid were detected by liquid chromatography/mass spectrometry (LC/MS). Adducts A and B were also the major products formed enzymatically when dGuo was incubated in the presence of linoleic acid and lipoxygenase. The mass spectral fragmentation patterns of adducts A and B suggested that unique modifications to the nucleoside had been introduced. This resulted in the characterization of a novel bifunctional electrophile, 4-oxo-2-nonenal, as the principal breakdown product of linoleic acid hydroperoxide. In subsequent studies, adduct A was found to be a substituted ethano dGuo adduct that was a mixture of three isomers (A(1)-A(3)) that all decomposed to form adduct B. Adduct A(1) was the hemiacetal form of 3-(2-deoxy-beta-D-erythropentafuranosyl)-3,5,6, 7-tetrahydro-6-hydroxy-7-(heptane-2-one)-9H-imidazo[1, 2-alpha]purine-9-one. Adducts A(2) and A(3) were the diastereomers of the open chain ketone form. Adduct B was the substituted etheno dGuo adduct, 3-(2-deoxy-beta-D-erythropentafuranosyl)imidazo-7-(heptane-2 -one)-9-hydroxy[1,2-alpha]purine, the dehydration product of adducts A(1)-A(3). Identical covalent modifications to dGuo were observed when calf-thymus DNA was treated with 4-oxo-2-nonenal. These data illustrate the diversity of reactive electrophiles produced from the peroxidative decomposition of lipids and have implications in fully assessing the role of lipid peroxidation in mutagenesis and carcinogenesis.

Aldehydes↗

Trichodinid ectoparasites (Ciliophora: Peritrichida) from the gills of cultured marine fishes in China, with the description of Trichodinella lomi n. sp.

Three species of cultured percoids, each heavily infested by trichodinid ectoparasites, were examined from over-wintering pools in Qingdao, China during the winter of 1995. A total of five species of trichodinids belonging to three genera, Trichodinella Sramek-Husek, 1953, Dipartiella Shtein, 1961 and Trichodina Ehrenberg, 1838 were recorded. One new species, Trichodinella lomi n. sp., is described, the denticle of which is characterised by its acutely triangular blade, comma-like central part and inconspicuous ray. The morphology of Trichodina murmanica Poljansky, 1955 was re-investigated. Three other little-known species are redescribed: Dipartiella simplex (Raabe, 1959) Shtein, 1961, Trichodina japonica Imai, Miyazaki & Nomura, 1991 and T. domerguei (Wallengren, 1897).

Animals↗

Trichodinid ectoparasites (Ciliophora: Peritrichida) from the gills of mariculture molluscs in China, with the descriptions of four news species of Trichodina Ehrenberg, 1838.

Four new species of the genus Trichodina, found on gills of marine molluscs from aquaculture beds off the coast of Qingdao (Tsingao), China, are described: T. chlamydis n. sp. from Azumapecten (Chlamys)farreri (Pectinidae), T. sinonovaculae n. sp. from Sinonovacula constricta (Solenidae), T. liana n. sp. from Solen (Plectosolen) gracilis (Solenidae) and T. meretricis n. sp. from Meretrix meretrix (Veneridae). The descriptions presented here include morphometric data obtained from examinations of specimens prepared using the wet silver nitrate and protargol-impregnation techniques. Comparisons with closely related species are provided for each of the four.

Animals↗