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Biomedical subjects

X Zhu

Publications and source records attributed to X Zhu.

At least 109 records · Page 6Linked to original sources

Racial differences and the genetics of hypertension.

Variation in the prevalence of hypertension among human populations has been used to examine a wide range of research questions. The best known example has always been the twofold greater prevalence among blacks, which has provoked a debate about the relative importance of environmental and genetic factors. This problem is complicated because it requires an understanding of both the genetics of hypertension and the genetic basis of variation among populations. Molecular data accumulated over the past year are beginning to provide new insights into this old question. Modest progress has now been made in the genetics of hypertension. Important advances have been made in understanding rare hypertension syndromes, and large-scale studies of the general population are under way, although the results to date are inconclusive. Markers used to search for hypertension genes can also provide estimates of between-population variability. These data, which are based on genetic variants used for etiologic research, confirm previous evidence of group-specific variation, while underscoring the limited magnitude of this variation. Despite rapid progress, this work is still in its infancy and raises more questions than it answers.

Black People↗

Hibernation, a model of neuroprotection.

Hibernation, a natural model of tolerance to cerebral ischemia, represents a state of pronounced fluctuation in cerebral blood flow where no brain damage occurs. Numerous neuroprotective aspects may contribute in concert to such tolerance. The purpose of this study was to determine whether hibernating brain tissue is tolerant to penetrating brain injury modeled by insertion of microdialysis probes. Guide cannulae were surgically implanted in striatum of Arctic ground squirrels before any of the animals began to hibernate. Microdialysis probes were then inserted in some animals after they entered hibernation and in others while they remained euthermic. The brain tissue from hibernating and euthermic animals was examined 3 days after implantation of microdialysis probes. Tissue response, indicated by examination of hematoxylin and eosin-stained tissue sections and immunocytochemical identification of activated microglia, astrocytes, and hemeoxygenase-1 immunoreactivity, was dramatically attenuated around probe tracks in hibernating animals compared to euthermic controls. No difference in tissue response around guide cannulae was observed between groups. Further study of the mechanisms underlying neuroprotective aspects of hibernation may lead to novel therapeutic strategies for stroke and traumatic brain injury.

Animals↗

Prokaryotically expressed Buthus martensii Karsch insect depressant toxin has insecticidal effects.

An insect depressant toxin Buthus martensii Karsch insect toxin 4 (BmK IT(4)) cDNA was cloned into the prokaryotic expression vector pSW202 and expressed in HB101 host cells. The authenticity of this in vitro expressed peptide was confirmed by Western blotting, mass spectrometry and N-terminal peptide sequencing. Bioassays using growth media supplemented with BmK IT(4) demonstrated that, at the end of the 5-day experimental period, about 77% of the testing cotton bollworm larvae were killed. Furthermore, the average weight picked up by larvae grown on BmK IT(4) containing media amounts only to 0.7% of that of control group. Our results indicate that BmK IT(4) may be used for biological control of insect damages in place of other traditional insecticides.

Amino Acid Sequence↗

Treatment of dye wastewater containing acid orange II using a cell with three-phase three-dimensional electrode.

The removal of color and chemical oxygen demand (COD) from simulated dye wastewater containing Acid Orange II was experimentally investigated using coagulation-electrooxidation. Two kinds of coagulation methods, ferrous-mediated coagulation and electrocoagulation were tested as pretreatment. The electrooxidation was carried out in a cell with a three-phase three-dimensional electrode using granular activated carbon as particle electrodes. Particular attention was paid to probe the effect of cell voltage, airflow rate, solution conductivity and treatment time on the electrochemical treatment efficiency. The experimental results showed that the coagulation-electrooxidation process could efficiently remove the color and the COD from the simulated dye wastewater. The overall COD and color removal efficiencies reached as high as 99% and 87%, respectively, by ferrous coagulation (molar rate of Fe(II)/ dye: 0.5) and 30-min electrolysis (cell voltage: 20.0 V and airflow: 0.1 m3 h(-1)).

Azo Compounds↗

Uptake and distribution of rare earth elements in rice seeds cultured in fertilizer solution of rare earth elements.

The uptake behavior of rare earth elements (REEs) under pot conditions using deionized water and a REE fertilizer solution as the culture media as well as the distribution of REEs in rice proteins were studied. The uptake of REEs in rice seeds increased dramatically after a lag period of approximately three days. Roots can accumulate a much higher content of REEs than germs and the resting seeds. The REE content in each water-soluble (albumin) and salt-soluble (globulin) component of the rice seeds accounted for 5-8% and 4-6% of the total REEs, respectively. However, there are less than 1.5% of the total REEs were found in the alcohol-soluble (prolamin) and acetic acid-soluble (glutelin) components. The high performance liquid chromatography (HPLC) in the gel permeation and the reserved-phase were used to monitor changes in the molecular weight distribution changes of the soluble proteins of rice seeds during germination after having been cultured in the same solution for seven days. No changes occurred in the prolamin, while a slight change occurred in the albumin, globulin and glutelin. Fractionation of the albumin of rice seeds cultured in a REE fertilizer solution on the Sephadex G-100 column indicated that REEs, especially Ce, La, Pr and Nd, were associated mainly with biological compounds of a molecular weight between 10,000 and 12,000.

Absorption↗

Neurons in Alzheimer disease emerge from senescence.

A number of cell cycle markers are associated with the selective neuronal pathology found in Alzheimer disease. However, the significance of such cell cycle markers is clouded by duplicity of function in that many such proteins are also involved in apoptosis and/or DNA repair following oxidative damage. To clarify whether or not neurons in Alzheimer disease do in fact emerge from a quiescent status, with subsequent entry into the G1 phase of the cell cycle, in this study we focused on a family of MORF4-related proteins that are associated with emergence from senescence. Our results show that many neurons in vulnerable regions of Alzheimer disease brain, but not in control brain, have increased MORF4-related proteins indicating re-entry into the cell cycle. Immunoblot analysis showed a specific disease-related increase in a 52 kDa protein that is likely the human homologue of the MORF4-related transcription factor. The novel localization of such a transcriptional activating protein to selectively vulnerable neurons in Alzheimer disease provides compelling evidence for mitotic re-entry as part of the pathogenesis of neuronal dysfunction and death in Alzheimer disease.

Acetyltransferases↗

Differential activation of neuronal ERK, JNK/SAPK and p38 in Alzheimer disease: the 'two hit' hypothesis.

There are multiple lines of evidence showing that oxidative stress and aberrant mitogenic signaling play an important role in the pathogenesis of Alzheimer disease. However, the chronological relationship between these and other events associated with disease pathogenesis is not known. Given the important role that mitogen-activated protein kinase (MAPK) pathways play in both mitogenic signaling (ERK) and cellular stress signaling (JNK/SAPK and p38), we investigated the chronological and spatial relationship between activated ERK, JNK/SAPK and p38 during disease progression. While all three kinases are activated in the same susceptible neurons in mild and severe cases (Braak stages III-VI), in non-demented cases with limited pathology (Braak stages I and II), both ERK and JNK/SAPK are activated but p38 is not. However, in non-demented cases lacking any sign of pathology (Braak stage 0), either ERK alone or JNK/SAPK alone can be activated. Taken together, these findings indicate that MAPK pathways are differentially activated during the course of Alzheimer disease and, by inference, suggest that both oxidative stress and abnormalities in mitotic signaling can independently serve to initiate, but both are necessary to propagate, disease pathogenesis. Therefore, we propose that both 'hits', oxidative stress and mitotic alterations, are necessary for the progression of Alzheimer disease.

Adolescent↗

Anodic oxide films containing Ca and P of titanium biomaterial.

Anodic oxidation and oxide films of titanium in the new electrolyte of calcium glycerophosphate (Ca-GP) and calcium acetate (CA) were investigated by galvanostatic mode, SEM, XRD and EPMA. The anodic oxide film displayed porosity, intermediate roughness, and high crystallinity. Also, the oxide film is enriched with Ca and P and high in thickness without microcracks. According to the surface properties of the oxide film, the optimum condition was that the concentration of the electrolyte was 0.02 M Ca-GP and 0.15 M CA, and current density and final voltage were 70 A/m2 and ca. 350 V. The oxide film formed in the condition is 0.98 microm (Ra) rough, 5-7 microm thick, adhesive to the underlying substrate, and near 1.67 Ca/P ratio in the oxide film.

Biocompatible Materials↗

Immune effects of hormone replacement therapy in post-menopausal women.

Hormone replacement therapy (HRT) confers many health benefits to post-menopausal women. Despite links between estrogen and immune function prior to menopause, the immune status of women receiving HRT has not been rigorously investigated. This case-control study uses clinical laboratory assessment, flow cytometry, and functional assays to measure immune function. Participants included 27 post-menopausal women taking estrogen/progestin combinations, and 22 post-menopausal women not receiving HRT. Compared to the (-)HRT group, the (+)HRT group had more B-cells (p<0.05), higher mitogen-induced T-cell proliferation (p<0.05), and higher levels of induced TNF-alpha (p<0.05). There was a trend towards a lower proportion of CD4+ T-cells expressing the activation marker CD25+ (p<0.10). These findings represent a reversal of immune alterations associated with normal aging, suggesting that preservation or improvement of immune function may be associated with the use of HRT.

Aged↗

N-terminal carboxyl and tetrazole-containing amides as adjuvants to Grb2 SH2 domain ligand binding.

High affinity binding of peptides to Src homology 2 (SH2) domains, often requires the presence of phosphotyrosyl (pTyr) or pTyr-mimicking moieties in the N-terminal position of the binding ligand. Several reports have shown that N(alpha)-acylation of the critical pTyr residue can result in increased SH2 domain binding potency. For Grb2 SH2 domains which recognize pTyr-Xxx-Asn-NH(2) motifs, significant potency enhancement can be incurred by N(alpha)-(3-amino)Z derivatization of tripeptides such as pTyr-Ile-Asn-NH(2). Using ligands based on the high affinity pY-Ac(6)c-Asn-(naphthylpropylamide) motif, (where Ac(6)c=1-aminocyclohexanecarboxylic acid), additional reports have shown moderate potentiating effects of N(alpha)-oxalyl derivatization. The current study examined variations of the N(alpha)-oxalyl theme in the context of a Xxx-Ac(6)c-Asn-(naphthylpropylamide) platform, where Xxx=the hydrolytically stable pTyr mimetics phosphonomethyl phenylalanine (Pmp) or carboxymethyl phenylalanine (Cmf). The effects of N(alpha)-(3-amino)Z derivatization were also investigated for this platform, to ascertain whether the large binding enhancement reported for tripeptides such as pTyr-Ile-Asn-NH(2) could be observed. In ELISA-based extracellular Grb2 SH2 domain binding assays, it was found for the Pmp-based series, that extending the oxalyl carboxyl out by one methylene unit or replacing carboxyl functionality with a tetrazole isostere, resulted in binding potency greater than the parent N(alpha)-acetyl-containing compound, with enhancement approximating that observed for the N(alpha)-oxalyl derivative. When Cmf was used as the pTyr mimetic, only modest differences in IC(50) values were observed for the series. Examination of the N(alpha)-(3-amino)Z derivatized Pmp-Ac(6)c-Asn-(naphthylpropylamide), showed that binding affinity was reduced relative to the parent N(alpha)-acetyl analogue, in contrast to the reported significant enhancement of affinity observed with other peptide ligands. Treatment of MDA-453 tumor cells, which are mitogenically driven through erbB-2 tyrosine kinase-dependent pathways, with Pmp-containing inhibitors resulted in growth inhibition, with the N(alpha)-oxalyl and N(alpha)-malonyl-containing compounds exhibiting IC(50) values (4.3 and 4.6 microM, respectively) approximately five-fold lower than the parent N(alpha)-acetyl-containing compound. Tetrazole and N(alpha)-(3-amino)Z-containing inhibitors were from two- to four-fold less potent than these latter analogues in the growth inhibition assays.

Adaptor Proteins, Signal Transducing↗

Lysine catabolism: a stress and development super-regulated metabolic pathway.

Lysine is a nutritionally important essential amino acid whose level in plants is largely regulated by the rate of its synthesis. In some plant tissues and under some stress conditions, however, lysine is also efficiently catabolized into glutamate and several other stress-related metabolites by novel mechanisms of metabolic regulation. Lysine catabolism is important for mammalian brain function; it is possible that the generation of glutamate regulates nerve transmission signals via glutamate receptors. Plants also possess homologues of animal glutamate receptors. It is thus likely that lysine catabolism also regulates various plant processes via these receptors.

Animals↗

Analysis of cooking oil fumes by ultraviolet spectrometry and gas chromatography-mass spectrometry.

This paper investigated the components, especially aldehydes, in the fume condensates from four kinds of cooking oil using ultraviolet (UV) spectrometry and gas chromatography-mass spectrometry (GC-MS). It was observed that there was a great change of the UV absorption spectra from the results of the unheated oil to the results of the fume after heat treatment (190-200, 230-240, and 270-280 degrees C). There was a strong peak within the wavelength range of 260-270 nm in each condensate sample. From the GC-MS results, it was tentatively deduced that there were some 2,4-dialkylenaldehydes and other conjugated compounds in the condensates. The results showed there were large amounts of hexanal and 2-heptenal in the cooking oil fume and that the total aldehyde peak areas of the condensates from four kinds of oil were around 30-50% of the total peak area at 270-280 degrees C.

Aldehydes↗

Blockade of eosinophil migration and airway hyperresponsiveness by cPLA2-inhibition.

We examined the role of a cytosolic phospholipase A2 (cPLA2) in antigen-induced eosinophil infiltration of airways and in airway hyperresponsiveness to methacholine. Inhibition of cPLA2, or blockade of the platelet-activating factor (PAF) receptor, blocked antigen-induced airway hyperresponsiveness and suppressed eosinophil infiltration. Neither cyclooxygenase nor 5-lipoxygenase inhibition had either effect. We show here that, in antigen-sensitized guinea pigs, cPLA2 inhibition prevents both eosinophilic infiltration and subsequent airway hyperresponsiveness after antigen challenge. We also show that this effect is mediated by first-step hydrolysis of membrane phospholipid into lysophospholipid rather than by prostanoid or leukotriene metabolites of arachidonate.

Animals↗

Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease.

Somatic inactivation of PTEN occurs in different human tumors including glioblastoma, endometrial carcinoma and prostate carcinoma. Germline mutations in PTEN result in a range of phenotypic abnormalities that occur with variable penetrance, including neurological features such as macrocephaly, seizures, ataxia and Lhermitte-Duclos disease (also described as dysplastic gangliocytoma of the cerebellum). Homozygous deletion of Pten causes embryonic lethality in mice. To investigate function in the brain, we used Cre-loxP technology to selectively inactivate Pten in specific mouse neuronal populations. Loss of Pten resulted in progressive macrocephaly and seizures. Neurons lacking Pten expressed high levels of phosphorylated Akt and showed a progressive increase in soma size without evidence of abnormal proliferation. Cerebellar abnormalities closely resembled the histopathology of human Lhermitte-Duclos disease. These results indicate that Pten regulates neuronal size in vivo in a cell-autonomous manner and provide new insights into the etiology of Lhermitte-Duclos disease.

Animals↗

The beta 3-adrenergic receptor gene and obesity in a population sample of African Americans.

OBJECTIVE: To examine the role of the Trp64Arg polymorphism in the beta 3-adrenergic receptor gene and the beta 3-adrenergic receptor gene locus in obesity-related traits in African Americans. SUBJECTS: A total of 687 individuals representing 193 African American families who were residents of metropolitan Chicago. MEASUREMENTS: Genotyping of the Trp64Arg polymorphism in the beta 3-adrenergic receptor gene and three microsatellite markers flanking the beta 3-adrenergic receptor gene (ADRB3) locus and measuring various obesity-related traits, including body mass index (BMI), fat-free mass, fat mass, percentage fat mass, waist circumference and serum lipid levels. RESULTS: The prevalence of obesity (defined as body mass index > or = 30 kg/m(2)) in the population was 27.3% and 51.2% in men and women, respectively. The frequency of the Arg64 allele was 10.0%. Multivariate regression analyses confirmed the existence of a significant contribution of familial variance to each of the five obesity-related traits noted above. Likelihood ratio statistics computed in a multivariate regression analysis failed to demonstrate a significant association between the Arg64 allele and any of the five obesity-related traits. Single and multipoint analyses using extended Haseman--Elston regression analyses failed to demonstrate suggestive evidence of linkage of three microsatellite markers that flank the beta 3-adrenergic receptor gene to BMI, percentage body fat, waist circumference or serum leptin levels. CONCLUSION: Given the contribution of familial variance to obesity-related traits in this population, neither the null finding for the Arg64 allele nor the lack of evidence of linkage of the ADRB3 locus to obesity-related traits could be attributed to lack of transmissibility of the traits suggesting that neither the Arg64 variant of the beta 3-adrenergic receptor gene nor another genetic variant in or near the ADRB3 locus contribute significantly to familial aggregation of obesity-related traits in African Americans. International Journal of Obesity (2001) 25, 54-60

Adipose Tissue↗

Heritability of obesity-related traits among Nigerians, Jamaicans and US black people.

OBJECTIVE: The mean values for anthropometric traits vary across population groups and this variation is clearly determined for the most part by the environment. The familiarity of anthropometric traits also varies in reports from different populations, although this variation has not been shown to follow a consistent pattern. To examine whether heritability is influenced by socio-cultural factors, we conducted a cross-cultural study of populations of the African diaspora. PARTICIPANTS: Data were collected on 1868 family members from Nigeria, 623 from Jamaica and 2132 from metropolitan Chicago, IL, USA. MEASUREMENTS: Height and weight were measured and body mass index (kg/m(2)) calculated. Fat-free mass, fat mass and percentage body fat were estimated using bioelectrical impedance analysis. Plasma leptin concentrations were also measured. The proportion of variance attributable to additive genetic and non-shared environmental components was estimated with the maximum likelihood variance decomposition method. RESULTS: Mean values for all anthropometric traits increased along the socio-cultural gradient, and obesity increased from 5% in Nigeria to 23% in Jamaica and 39% in the USA. Within populations the relationships among traits both within individuals and within families were highly consistent. Heritability estimates for weight, body mass index, fat mass and percentage body fat were approximately 50% for all groups. Heritability for height was lower in Nigeria (62%) than in Jamaica (74%) or the US (87%). CONCLUSION: The familial patterns of body size and energy storage appear to be consistent in these genetically related populations across a wide range of environmental conditions.

Adult↗

Multiple virulence factors of Cryptococcus neoformans are dependent on VPH1.

Acidification of vesicular compartments plays an important role in a number of cellular transport processes, including protein secretion, metal cofactor insertion, glycosylation and pH stability. In the present study, we identify and characterize a component of the vesicular proton pump, Vph1p, to determine its role in the virulence of the AIDS-related fungal pathogen Cryptococcus neoformans. Insertional mutagenesis and plasmid rescue were used to identify the VPH1 gene by screening for mutants defective in laccase activity. Disruption of VPH1 resulted in defects in three virulence factors (capsule production, laccase and urease expression), as well as a growth defect at 37 degrees C, but only a small growth reduction at 30 degrees C. These effects were duplicated by the vacuolar (H+)-ATPase inhibitor bafilomycin A1. Furthermore, the vph1 insertional mutant was also avirulent in a mouse meningo-encephalitis model. Complementation of the insertional mutant with wild-type VPH1 resulted in a recovery of virulence factor expression, normal growth at 37 degrees C and restoration of full virulence. These studies establish the importance of the VPH1 gene and vesicular acidification in the virulence of C. neoformans.

AIDS-Related Opportunistic Infections↗