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Biomedical subjects

E Wei

Publications and source records attributed to E Wei.

At least 19 recordsLinked to original sources
PubMed2005

Corticotropin-releasing hormone triggers differentiation in HaCaT keratinocytes.

BACKGROUND: Corticotropin-releasing hormone (CRH) is proposed to be involved in the regulation of the proliferative capacity of keratinocytes, based on its significant actions in the skin. These are mediated by CRH-R1alpha and represented by adenylate cyclase activation, Ca2+ influx, inhibition of cell proliferation and modifications in intracellular signal transduction by NF-kappaB. OBJECTIVES: To define CRH action in the cell cycle we investigated its effects on the differentiation programme using the HaCaT keratinocytes model. METHODS: HaCaT keratinocytes were incubated with CRH in Dulbecco's modified Eagles's medium (containing 1.8 mmol L(-1) calcium) or EpiLife (containing 0.06 mmol L(-1) calcium) medium. Cell proliferation was assessed with the MTT assay. Flow cytometry was used for the measurement of DNA content, cell size and granularity and the expression of cytokeratin 14, cytokeratin 1 and involucrin. The electrophoretic mobility shift assay was used to determine DNA binding activity by AP-1 transcription factor. Expression of cytokeratin 1 was also assessed with immunofluorescence microscopy. RESULTS: CRH did produce inhibition of proliferation, which was dose-dependent; the shape of the inhibition curve was determined by the media calcium concentration. CRH action was pinpointed at inhibition of the G0/1 to the S phase transition of the cell cycle. CRH also increased AP-1 binding activity, cell granularity, cytokeratin 1 and involucrin expression, and inhibited cytokeratin 14 expression. CONCLUSIONS: These results are consistent with CRH induction of the keratinocyte differentiation programme. Thus, the overall CRH cutaneous actions connote protective functions for the epidermis, that appear to include the triggering or acceleration of the differentiation programme.

Cell Differentiation↗
PubMed2001

Murine phosphatidylserine-specific phospholipase A1 (Ps-pla1) maps to chromosome 16 but is distinct from the lpd (lipid defect) locus.

We have previously generated a mouse transgenic line with an insertional mutation designated lpd that demonstrates a phenotype of hypertriglyceridemia and fatty liver. Since the recently identified phosphatidylserine-specific phospholipase A1 (PS-PLA1) demonstrates significant homology to triglyceride lipases, we reasoned that the mouse Ps-plaI gene may be the disrupted gene within the lpd locus. Using a rat PS-PLA1 cDNA sequence to search the EST database, we identified a mouse EST homolog AA839424. Sequencing analysis of AA839424 revealed a putative Ps-pla1 protein of 456 amino acids with extensive overall structural conservation with human and rat PS-PLA1 and with triglyceride lipases. Conserved sequences in Ps-pla1 include a lipase consensus sequences GxSxG, a catalytic triad, and eight of the ten conserved cysteine residues that are required for tertiary structure. Mouse Ps-plal carries a phosphatidylserine-binding motif that is absent in all triglyceride lipases. Using a mouse whole-genome radiation hybrid (WG-RH) mapping panel (T31), we mapped mouse Ps-pla1 to Chromosome (Chr) 16 between genetic markers D16Mit194 and D16Mit38, which is 17.1 cM centromeric to the lpd locus. On the basis of chromosome location, we conclude that Ps-pla1 and lpd are distinct genes in lipid metabolism.

Amino Acid Sequence↗
PubMed2001

Pleiotropic effects of corticotropin releasing hormone on normal human skin keratinocytes.

The hypothalamic-pituitary-adrenal (HPA) axis is the major stress response system. Several components of the HPA axis, such as corticotropin-releasing hormone (CRH) and POMC peptides and their receptors are also present in the skin. In earlier studies, we showed that CRH inhibits cellular proliferation of immortalized human keratinocytes. We now examine further the functional activity of the HPA axis in the skin, by characterizing the actions of CRH on normal foreskin keratinocytes. The CRH receptor was detected as CRH-R1 antigen at 47 kDa in the cultured keratinocytes by Western blotting, and immunohistochemistry demonstrated its presence in the epidermal and follicular keratinocytes. CRH is also biologically active in cultured keratinocytes, where it inhibits proliferation and enhances the interferon-gamma-stimulated expression of the hCAM and ICAM-1 adhesion molecules and of the HLA-DR antigen. These effects were concentration-dependent, with maximal activity at CRH 10(-7) M. Thus, in the keratinocyte, the most important cellular component of the epidermis, CRH appears to induce a shift in energy metabolism away from proliferation activity, and toward the enhancement of immunoactivity. Therefore, similar to its central actions, cutaneous CRH may also he involved in the stress response, but at a highly localized level.

Blotting, Western↗
PubMed2001

Maltreatment of boys and the development of disruptive and delinquent behavior.

Data from a longitudinal, inner-city community sample were used to examine the prevalence of child maltreatment in males and to relate this to disruptive and delinquent child behavior. By age 18 years, almost one fourth of the families had been referred to Children and Youth Services (CYS). Investigation by the CYS resulted in substantiated maltreatment of 10% of the participants, mostly for physical abuse and neglect. Almost all maltreatment was perpetrated by people living in the same house as the victim. Maltreatment was related to the boys progressing on three pathways in disruptive and delinquent behavior: authority conflict pathway, overt pathway, and covert pathway. Two thirds of the victims showed authority conflict problems, and almost all of the maltreated boys displayed behaviors characteristic of the overt and covert pathways. Victims, compared to matched controls, were more likely to have engaged in behaviors characteristic of the authority conflict and the overt pathways but less strongly engaged in behaviors associated with the covert pathway. Victims were also more likely than controls to have a referral to juvenile court. Most of the CYS contact tended to precede or co-occur with onset of overt and covert problem behavior, but about half of the onset of authority conflict behaviors tended to precede contact with CYS.

Adolescent↗
PubMed2001

Family-based association test method: age of onset traits and covariates.

We apply different family-based association test (FBAT) statistics for age of onset traits to the Genetics Analysis Workshop 12, problem 2 data. To evaluate different FBAT statistics we used the software package FBAT, which allows one to evaluate any test statistic that can be expressed as the sum of products between an arbitrary function of an offspring's genotype with an arbitrary function of the offspring's phenotype even if there are missing parental information. For single nucleotide polymorphisms (SNPs) in gene 1, our age-of-onset FBAT test based on the exponential model is significantly more powerful than the test by Mokliatchouk et al. [Hum Hered 51:46-53, 2000], which is based on the Cox model. We suggest incorporating covariates into FBAT statistics by replacing the trait values by their regression residuals. For the age of onset trait statistics we find that deviance residuals have much more power than "plain" martingale residuals. We discuss why for SNPs in gene 1, the usual affectation status trait, which underlies the transmission disequilibrium test (TDT), has higher power than the age-of-onset trait. We find only weak evidence (p = 0.0002) that marker D06G032 is associated with the affectation status.

Adult↗
PubMed2000

Effects of resveratrol on oxidative modification of human low density lipoprotein.

OBJECTIVE: To determine the antioxidative effects of resveratrol (RES), a polyphenolic compound in red wine, on the oxidation of human low density lipoprotein (LDL) using two different oxidation systems. METHODS: Oxidation of LDL was induced by adding either Cu2+ or an azo compound. The extent of LDL modification was assessed by measuring the formation of thiobarbituric acid reactive substances (TBARS), the relative electrophoretic mobilities (REM), and the amount of oxidized LDL degradation by macrophages. RESULTS: During Cu(2+)-induced oxidation, RES reduced TBARS formation in LDL by 70.5%, REM of LDL by 42.3% and the amount of macrophage degradation by 65.7%, respectively. The lag phase of LDL oxidation was also delayed by adding RES both in the copper ion and azo compound-induced oxidation systems. CONCLUSION: RES can protect LDL against both Cu(2+)-induced and azo compound-initiated oxidative modification in vitro, which might be due to its free radical scavenging capacity.

Animals↗
PubMed1999

Cutaneous expression of CRH and CRH-R. Is there a "skin stress response system?".

The classical neuroendocrine pathway for response to systemic stress is by hypothalamic release of corticotropin releasing hormone (CRH), subsequent activation of pituitary CRH receptors (CRH-R), and production and release of proopiomelanocortin (POMC) derived peptides. It has been proposed that an equivalent to the hypothalamic-pituitary-adrenal axis functions in mammalian skin, in response to local stress (see Reference 1). To further define such system we used immunocytochemistry, RP-HPLC separation, and RIA techniques, in rodent and human skin, and in cultured normal and malignant melanocytes and keratinocytes. Production of mRNA for CRH-R1 was documented in mouse and human skin using RT-PCR and Northern blot techniques; CRH binding sites and CRH-R1 protein were also identified. Addition of CRH to immortalized human keratinocytes, and to rodent and human melanoma cells induced rapid, specific, and dose-dependent increases in intracellular Ca2+. The latter were inhibited by the CRH antagonist alpha-helical-CRH(9-41) and by the depletion of extracellular calcium with EGTA. CRH production was enhanced by ultraviolet light radiation and forskolin (a stimulator for intracellular cAMP production), and inhibited by dexamethasone. Thus, evidence that skin cells, both produce CRH and express functional CRH-R1, supports the existence of a local CRH/CRH-R neuroendocrine pathway that may be activated within the context of a skin stress response system.

Animals↗
PubMed1999

Angiotensinogen gene polymorphisms M235T/T174M: no excess transmission to hypertensive Chinese.

The gene encoding angiotensinogen (AGT) has been widely studied as a candidate gene for hypertension. Most studies to date have relied on case-control analysis to test for an excess of AGT variants among hypertensive cases compared with normotensive controls. However, with this design, nothing guarantees that a positive finding is due to actual allelic association as opposed to an inappropriate control population. To avoid this difficulty in our study of essential hypertension in Anqing, China, we tested AGT variants using the transmission/disequilibrium test, a procedure that bypasses the need for a control sample by testing for excessive transmission of a genetic variant from parents heterozygous for that variant. We analyzed two AGT polymorphisms, M235T and T174M, which have been associated with essential hypertension in whites and Japanese, using data on 335 hypertensive subjects from 315 nuclear families and their parents. Except in the group of subjects younger than 25 years, M235 and T174 were the more frequently transmitted alleles. We found that 194 parents heterozygous for M235T transmitted M235 106 times (P=0.22) and that 102 parents heterozygous for T174M transmitted T174 60 times (P=0.09). Stratifying offspring by gender, M235 and T174 were transmitted 60 of 106 times (P=0.21) and 44 of 75 times (P=0.17), respectively, in men, and 46 of 88 times (P=0.75) and 16 of 27 times (P=0.44), respectively, in women. Our results were also negative in all age groups and for the affected offspring with blood pressure values >/=160/95 mm Hg. Thus, this study provides no evidence that either allele of M235T or T174M contributes to hypertension in this Chinese population.

Adult↗
PubMed1997

Interactions between macrophages and oxidized low density lipoprotein in the presence of type I collagen.

In order to investigate the influence of collagen on the interactions between macrophages and oxidatively modified low density lipoprotein (ox-LDL), type I collagen was isolated from rat tail tendon and prepared as a gel. The binding of 125I-ox-LDL, 125I-malondialdehyde (MDA)-LDL and 125I-acetyl-LDL to collagen was higher but the binding of 125I-4-hydroxynonenal (HNE)-LDL was lower than that of native 125I-LDL. When mouse peritoneal macrophages were cultivated on this collagen gel, most of the modified LDL was bound to the collagen gel rather than taken up by macrophages. The amount of modified 125I-LDL degraded by the macrophages decreased in the presence of the collagen gel. In the absence of gel a similar degree of reduction in degradation of modified 125I-LDL by macrophages was obtained when the cells were treated with cytochalasin D, an inhibitor of non-specific phagocytosis. However, the treatment of the macrophages cultivated on the collagen gel with cytochalasin D did not influence the degradation of 125I-ox-LDL and 125I-HNE-LDL. These results suggest that the uptake of ox-LDL by macrophages grown on collagen gel is primarily mediated via the scavenger receptors pathway, whereas in the absence of collagen also other mechanisms of uptake are operating.

Animals↗
PubMed1997

[Determination of airway reactivity in the conscious and unrestrained guinea pigs].

A simple, stable determining system in the conscious and unrestrained guinea pigs was established that can quantitatively analyse the airway reactivity (AR). In this model, the response to histamine (His) or acetylcholine (ACh) aerosol was concentration-dependent with EC50 effective concentration causing 50% animals wheezing) of 53.3 mumol/m3 and 269 mumol/m3 respectively.

Acetylcholine↗
PubMed1997

[Diagnosis and treatment of postrenal acute renal failure].

52 cases of postrenal acute renal failure (ARF) from 1985 to 1995 were studied. 50 cases underwent emergency operation, and 2 were drained with ureter intubation by cystoscope. 37 cases (71.2%) were cured, 14 (26.9%) were improved, and 1 (1.9%) died. Oliguria, anuria and progressive increase of blood urea nitrogen and serum creatinine are the main points of diagnosis. Renal percussive pain is the important sign. B-ultrasonography examination is the first choice and often indicate the increase of the volume of kidney and mild hydronephrosis. Obstruction should be removed as quickly as possible, infection should be prevented and treated to protect renal function. The way of treatment should be adopted according to the variant causes and conditions of disease. The etiology, clinical findings, diagnosis, operating methods and cautions were discussed.

Acute Kidney Injury↗
PubMed1986

Analysis of cardiovascular effects of morphine in the cat.

In cats anaesthetized with chloralose, the effect of morphine on arterial blood pressure and heart rate was examined by injecting the drug through different routes. When injected into the cerebral ventricles, it acted on structures in the walls of the third ventricle and produced a naloxone resistant tachycardia through a sympathetic discharge to the heart. When injected into the cisterna magna or subcutaneously, it produced a naloxone sensitive long-lasting fall in blood pressure and bradycardia resulting from inhibition of sympathetic tone to blood vessels and heart; increased vagal tone played a minor role in the development of bradycardia. When injected intracisternally or subcutaneously, morphine acted near the obex at the dorsal surface of the medulla, because it produced the same circulatory effects but in much smaller doses when applied to this region on a piece of filter paper. Conversely, small doses of naloxone similarly applied abolished or prevented the circulatory effects of subcutaneous morphine. The action of morphine may be on the commissural nucleus of the tractus solitarius. Intravenous naloxone restored the circulatory effects of intracisternal and subcutaneous morphine and sometimes produced a pronounced overshoot, but without a preceding injection of morphine, naloxone had no effect on circulation. It is suggested that inhibition of sympathetic tone to the cardiovascular system by an action on structures near the obex is the mechanism by which morphine produces in man orthostatic hypotension and its beneficial effect in left ventricular failure.

Animals↗
PubMed1985

In vivo evidence for the selectivity of ICI 154129 for the delta-opioid receptor.

The in vivo selectivity of the novel delta opioid-receptor antagonist N,N-bisallyl-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH (ICI 154129) was examined in several opioid-selective models. Antagonism at the delta receptor was demonstrated in the striatal head-turn model in the rat. Intrapallidal injection of the relatively selective delta-receptor agonist D-Ala2,D-Leu5-enkephalin (0.5 micrograms) slowed the head-turn time and this effect was completely prevented by prior subcutaneous administration of ICI 154129 (30 mg/kg). The role of delta receptors in two classical test situations was studied using the mixed opioid agonist etorphine and the antagonists naloxone and ICI 154129. The drug ICI 154129 (30 mg/kg, s.c.) failed to prevent the antinociceptive effects and stimulation of locomotor activity produced by etorphine, whereas the relatively selective mu-opioid receptor antagonist, naloxone was effective in both test situations. The possible involvement of delta receptors in morphine-induced dependence was studied by monitoring the abstinence behaviour precipitated in rats given pellets of morphine by either ICI 154129 or naloxone. Naloxone (0.5 mg/kg, i.p.) precipitated a characteristic withdrawal syndrome in conscious rats and, at a much smaller dose (0.02 mg/kg, i.p.), induced shaking behaviour in pentobarbitone-anaesthetised rats. No withdrawal signs were observed in either model after injection of ICI 154129 (30 mg/kg, s.c.), suggesting that the delta receptors are not involved in dependence on morphine.

Analgesics↗
PubMed1979

Cardiovascular effects of hypertonic sodium chloride solutions when injected into the liquor space of anaesthetized cats.

1 In cats anaesthetized with chloralose, hyper- and hypotonic solutions were injected into the cisterna magna (in 0.5 ml) or into a lateral cerebral ventricle (in 0.2 to 0.3 ml), with aqueduct cannulated to prevent the injected solution from entering the subarachnoid space, and the effects on blood pressure and heart rate were examined. 2 Cisternal injections of hyper- and hypotonic solutions of NaCl (0.51 M and 0.05 M), glucose (1.03 M and 0.10 M), or sucrose (1.02 M and 0.10 M), as well as distilled water produced a rise in arterial blood pressure with tachycardias. Isotonic solutions of NaCl, glucose or sucrose were ineffective. 3 Ventricular injections of the hypertonic NaCl solution, also produced a pressor response with tachycardia effects when injected in this way. 4 The pressor responses and the tachycardias occurred after bilateral vagotomy and resulted from a sympathetic discharge which, on cisternal injection, originated from structures reached from the subarachnoid space, and on ventricular injection, from structures in the ventricular walls, probably in the hypothalamus. 5 The stimuli responsible for the discharge, were, on cisternal injection, the changes in osmolarity and on ventricular injection, the sodium ions.

Anesthesia↗
PubMed1978

Endorphins may function in heat adaptation.

Administration of the opiate antagonist naloxone to rats after acute or chronic heat exposure precipitates an increase in colonic temperature, an increase in escape attempts, and a decrease in body weight. These changes are accompanied by signs associated with hyperthermia such as salivation, diarrhea, and an abnormal extended posture. Although brain endorphin involvement is possible, hypophysectomy diminishes the intensity and magnitude of these naloxone effects, indicating that the naloxone effect in intact animals may be due to a functional antagonism of pituitary endorphins. These observations suggest that endorphins attenuate physiological responses to thermal and noxious stimuli triggered in common neuroanatomical pathways by heat.

Adaptation, Physiological↗
PubMed1978

Quinoline: conversion to a mutagen by human and rodent liver.

Quinoline, a hepatocarcinogen in rats, and 23 quinoline derivatives were tested for mutagenic activity with the Ames Salmonella typhimurium assay. Quinoline, 5-hydroxyquinoline, and 8-hydroxyquinoline were mutagenic in strain TA 100 when Aroclor 1254-induced rat (male outbred Sprague-Dawley) liver homogenate was present in the incubation mixture. Enzyme preparations from rats pretreated with P-448-dependent aryl hydrocarbon hydroxylase inducers [3-methylcholanthrene (MCA) and beta-naphthoflavone] and MCA-treated "responsive" C57BL mice also metabolized quinoline to a mutagen, but phenobarbital and pregnenolone-16alpha-carbonitrile pretreatment did not yield active preparations. The mutagenicity of quinoline was blocked by the in vitro addition of menadione, butylated hydroxytoluene, alpha-naphthoflavone, vitamin A acetate, and glutathione to the test system. Depletion of glutathione by diethyl maleate pretreatment in vivo enhanced the mutagenic potential of the liver enzyme preparation. Mutagenic activity was correlated to the formation of water-soluble quinoline metabolites, and we suggested that the reactive quinoline intermediate is quinoline-2,3-epoxide. Microsomal enzymes isolated from human liver tissue, but not lung tissue, also converted quinoline to a mutagen.

Animals↗