Biomedical subjects

W Zhu

Publications and source records attributed to W Zhu.

At least 19 recordsLinked to original sources

PubMed2007

The expression analysis of ICOS-L on activated T cells and immature dendritic cells as well as malignant B cells and Grave's-disease-derived thyroid tissues by two novel mAbs against human ICOS-L.

ICOS-L, a newly identified member of B7 superfamily, plays an important role in immune responses. In this article, we report on two novel mouse anti-human ICOS-L monoclonal antibodies (mAbs) named as 11C4 and 12B11, whose specificities were verified by methods of flow cytometry, western blotting, and epitope competition assay. The two mAbs bound to distinct ICOS-L epitopes on B cells. Interestingly, mAb 11C4 could well recognize ICOS-L molecule on activated T cells and Jurkat cell lines, which is different from commercial anti-ICOS-L mAb (clone number MIH12) and the other mAb 12B11. In addition, we found that the expression of ICOS-L molecule was only detected on the surface of immature monocyte-derived dendritic cells (Mo-DCs) and was sharply decreased after induction of mature Mo-DCs activated by tumor necrosis factor-alpha or CD40. Furthermore, we showed that 11C4 could effectively suppress the maturation of Mo-DCs in vitro as evidenced by the low expression of CD80, CD86, CD83, and human leukocyte antigen-DR, which suggested that ICOS-L may be involved in the maturation of Mo-DCs. Using immunohistochemistry staining with mAb 11C4, the expression of ICOS-L was found in B lymphoma tissues and thyroid tissues from the Grave's disease but not in thyroid adenoma and normal thyroid tissues.

Animals↗

PubMed2006

Observation of plasma toroidal-momentum dissipation by neoclassical toroidal viscosity.

Dissipation of plasma toroidal angular momentum is observed in the National Spherical Torus Experiment due to applied nonaxisymmetric magnetic fields and their plasma-induced increase by resonant field amplification and resistive wall mode destabilization. The measured decrease of the plasma toroidal angular momentum profile is compared to calculations of nonresonant drag torque based on the theory of neoclassical toroidal viscosity. Quantitative agreement between experiment and theory is found when the effect of toroidally trapped particles is included.

Journal Article↗

PubMed2006

Efficacy of local dipyridamole therapy in a porcine model of arteriovenous graft stenosis.

Perivascular delivery of antiproliferative drugs has been proposed as an approach to prevent neointimal hyperplasia associated with hemodialysis polytetrafluoroethylene (PTFE) grafts. We examined this approach to deliver dipyridamole in a porcine graft model. PTFE grafts were implanted between the carotid artery and external jugular vein bilaterally in pigs. During the surgery or 1 week post-graft placement, dipyridamole (0.26-52 mg) alone or incorporated in microspheres was mixed with an injectable polymeric gel and applied to the graft-arterial and graft-venous anastomoses on one side, whereas the contralateral control graft received no treatment. Three or four weeks after operation, the grafts and adjacent vessels were explanted en bloc and cross-sections of the anastomoses were examined histologically. The degree of neointimal hyperplasia was quantified by planimetry. In separate experiments, dipyridamole was extracted from the explanted tissues and assayed by spectrofluorometry. The normalized median hyperplasia areas of the treated and control graft-venous anastomoses were 0.45 (25th-75th percentile, 0.30-0.86) and 0.24 (0.21-0.30), respectively (N=7; P=0.08). The median hyperplasia areas of the treated and control graft-arterial anastomoses were 0.12 (0.07-0.39) and 0.11 (0.09-0.13), respectively (N=7; P=0.31). The dipyridamole levels in the vascular walls around the anastomoses were at or above the in vitro inhibitory concentrations for approximately 3 weeks. These results suggest that the local perivascular sustained delivery of dipyridamole, even at high dosages, was ineffective in inhibiting neointimal hyperplasia associated with PTFE grafts in a porcine model.

Animals↗

PubMed2006

Antiviral property and mechanisms of a sulphated polysaccharide from the brown alga Sargassum patens against Herpes simplex virus type 1.

A sulphated polysaccharide (SP-2a) from the brown alga Sargassum patens (Kütz.) Agardh (Sargassaceae) was found to significantly inhibit the in vitro replication of both the acyclovir (ACV)-sensitive and -resistant strains of Herpes simplex virus type 1 (HSV-1), in dose-dependent manners, with 50% inhibitions occurring with 1.5-5.3 microg/ml of the polysaccharide. SP-2a exhibited extracellular virucidal activity only against the ACV-sensitive strains, but not the resistant strain, at the concentration of 100 microg/ml. The strongest antiviral activities against the different strains of HSV-1 were observed when this polysaccharide was present during and after adsorption of the virus to host cells. The inhibitory effect of SP-2a on virus adsorption occurred dose-dependently in all the HSV-1 strains tested, and the adsorption of the ACV-resistant DM2.1 strain was reduced by 81.9% (relative to control) with 4 microg/ml of the polysaccharide. This study clearly demonstrated that the antiviral mode of action of SP-2a is mediated mainly by inhibiting virus attachment to host cells, and this sulphated polysaccharide might have different modes of action against the ACV-sensitive and -resistant strains of HSV-1.

Acyclovir↗

PubMed2006

Unrelated donor bone marrow transplantation for beta-thalassemia major: an experience from China.

Although related bone marrow transplantation (BMT) is effective for thalassemia, less than 30% of patients have sibling donors. Here, we report unrelated BMT in nine thalassemic children using a high-resolution HLA typing technique to identify donors. HLA mismatches between donors and recipients were 0, 1 and 2 in 2, 5 and 2 cases, respectively. The results showed that white blood cells, platelets and hemoglobin all returned to normal at various time points, and blood transfusion was eliminated from 13 to 62 days after transplantation. Full engraftment was achieved in eight patients while ABO blood types were replaced with that of donors in five of the six ABO mismatched recipients. Acute skin GVHD was found in seven patients and acute liver GVHD in one. One patient with acute intestinal GVHD eventually developed chronic GVHD. One patient died of pulmonary hemorrhage in spite of having a fully functional graft. We conclude that this is the first successful application of unrelated BMT for thalassemia major in Chinese people and that the results will certainly expand donor resources and greatly enhance the survival and quality of life of thalassemic patients.

ABO Blood-Group System↗

PubMed2006

A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial of a long-acting formulation of octreotide in promoting weight loss in obese adults with insulin hypersecretion.

OBJECTIVE: To compare changes in weight in obese patients who received long-acting octreotide (octreotide LAR) at one of three dose levels (20, 40, or 60 mg) or placebo over 6 months and to identify the lowest dose of octreotide LAR that safely achieved optimal weight loss. DESIGN: Randomized, double-blind, placebo-controlled trial of octreotide LAR at three dose levels. PATIENTS: A total of 172 adults (28 men and 144 women) with at least moderate obesity (body mass index (BMI) range 30-65 kg/m2) and evidence of insulin hypersecretion were enrolled. Patients were predominantly either Caucasian (50.0%) or African American (45.3%). The mean age (38 +/- 11 year), weight (110.7 +/- 23 kg), and BMI (39.8 +/- 6.5 kg/m2) were similar across the four treatment groups. MEASUREMENTS: Efficacy measures included weight, BMI, fasting serum glucose; triglycerides; percentage of total body fat and abdominal fat as measured by dual-energy X-ray absorptiometry; skin fold thickness; waist-to-hip circumference; leptin; percentage of carbohydrates, fat, and protein ingested; nutritional evaluation (including dietary analysis--3-day food record); quality of life (QoL; using the Impact of Weight on Quality of Life-Lite); Beck Depression Inventory; and Carbohydrate Craving Questionnaire. Safety measures included medical history, vital signs, physical examinations, hematology, blood chemistries, thyroid function tests, hemoglobin A1c, gallbladder ultrasound, electrocardiograms, and adverse events. RESULTS: After 6 months of treatment, patients receiving 40 or 60 mg of octreotide LAR experienced statistically significant weight loss compared to baseline, with mean differences from placebo in percent weight change of -1.98 and -1.87%, respectively. This finding was accompanied by statistically significant mean decreases in BMI compared to baseline, that is, a mean decrease of 0.73 and 0.79 kg/m2 for the 40 and 60 mg treatment arms, respectively. The observed weight loss was progressive during the 6-month treatment in the two higher dose groups. The lowest dose to reach statistical significance in weight loss after 6 months' treatment was 40 mg. Post hoc analysis revealed a 3.5-3.8% weight loss at month 6 in the two higher dose groups among Caucasian patients having insulin secretion greater than the median of the cohort, defined as CIR(gp) (corrected insulin response at the glucose peak) > or = 1.43. There were no statistically significant changes in QoL scores, body fat, leptin concentration, Beck Depression Inventory, or macronutrient intake. Mean changes of blood glucose AUC(0-180 min) during an oral glucose tolerance test in patients taking octreotide LAR were 39-40 mg/dl h higher than those on placebo. A total of 7-21% of the patients taking octreotide LAR reached a 5% or greater decrease in body weight from Baseline, compared to 11% for the placebo group. This was not statistically significant. The most common adverse events included diarrhea, headache, cholelithiasis, nausea, and abdominal pain. CONCLUSION: Octreotide LAR given at 40 or 60 mg resulted in statistically significant weight loss. A post hoc analysis stratifying patients by race and CIR(gp) indicated that Caucasian patients with the greater degree of insulin hypersecretion appeared to derive the most benefit from treatment. The observed safety profile was consistent with the known effects of octreotide from previous studies.

Adult↗

PubMed2006

Absorption characteristics of EC-MPS--an enteric-coated formulation of mycophenolic sodium.

UNLABELLED: Enteric-coated mycophenolate sodium is an advanced formulation delivering mycophenolic acid (MPA), designed to improve MPA-related upper gastrointestinal adverse events by delaying MPA release until the small intestine. OBJECTIVE: Two studies were undertaken to identify the absolute bioavailability and dose-proportionality of enteric-coated mycophenolate sodium in stable renal transplant patients receiving cyclosporine. METHODS: Study 1: The mean MPA AUC(0-t) was shown to be greater after MPA infusion than after oral enteric-coated mycophenolate sodium (42.1 vs. 28.9 microg x h/ml). Mean absolute bioavailability was 0.71 +/- 0.21 (SD). Study 2: The AUC(0-t) and C(max) for MPA were proportional to the dose of enteric-coated mycophenolate sodium, similarly mean AUC(0-infinity) and C(max) for MPA glucuronide were proportional to dose administered. RESULTS AND CONCLUSIONS: In patients receiving cyclosporine the absolute bioavailability of MPA provided by enteric-coated mycophenolate sodium is equivalent to that provided by mycophenolate mofetil when administered in combination with cyclosporine, and exhibits dose-proportionality. Enteric-coated mycophenolate sodium was well tolerated from 180 - 2,160 mg with no serious adverse events reported.

Administration, Oral↗

PubMed2005

Reduction of neural and vascular damage by transplantation of VEGF-secreting neural stem cells after cerebral ischemia.

We determined the role of VEGF-transfected neural stem cells (NSCs) transplantation in rat brain subjected to ischemia. Fetal NSCs were cultured from E14 days SD rats and transfected with VEGF121 gene by using lipofectamine technique. Temporary middle cerebral artery occlusion (tMCAO) models were established and randomly divided into 1: control group, 2: PBS transplantation group, 3: NSCs transplantation group and 4: VEGF-secreting NSCs transplantation group. Grafts were transplanted into the penumbra zones 3 days after tMCAO model established. Neurological Severity Score (NSS) was checked in all groups 2-12 weeks after transplantation. By using immunofluorescent staining, VEGF expression of transplanted cells, differentiation and migration of transplanted NSCs after transplantation were detected. VEGF gene-transfected neural stem cells expressed gene products during the first 2 weeks. NSS in this group was significantly lower compared with that in other 3 groups 12 weeks after transplantation. VEGF gene-transfected NSCs migrated and expressed VEGF in hosts' brains, some of them differentiated to neurons 12 weeks after transplantation. VEGF-transfected NSCs expressed gene products during the early time after transplantation, which reduce brain injury through protecting the vascular system against ischemic attack.

Animals↗

PubMed2005

Mu-opioid-mediated inhibition of glutamate synaptic transmission in rat central amygdala neurons.

The central nucleus of the amygdala (CeA) plays an important role both in stimulus-reward learning for the reinforcing effects of drugs of abuse and in environmental condition-induced analgesia. Both of these two CeA functions involve the opioid system within the CeA. However, the pharmacological profiles of its opioid receptor system have not been fully studied and the synaptic actions of opioid receptors in the CeA are largely unknown. In this study with whole-cell voltage-clamp recordings in brain slices in vitro, we examined actions of opioid agonists on glutamate-mediated excitatory postsynaptic currents (EPSCs) in CeA neurons. Opioid peptide methionine-enkephalin (ME; 10 microM) produced a significant inhibition (38%) in the amplitude of evoked EPSCs, an action mimicked by the mu-opioid receptor agonist [D-Ala(2),N-MePhe(4),Gly-ol(5)]-enkephalin (DAMGO; 1 microM, 44%). Both effects of ME and DAMGO were abolished by the mu receptor antagonist CTAP (1 microM), suggesting a mu receptor-mediated effect. Neither delta-opioid receptor agonist [D-Pen(2),D-Pen(5)]-enkephalin (1 microM) nor kappa-opioid receptor agonist U69593 (300 nM) had any effect on the glutamate EPSC. ME significantly increased the paired-pulse ratio of the evoked EPSCs and decreased the frequency of miniature EPSCs without altering the amplitude of miniature EPSCs. Furthermore, the mu-opioid inhibition of the EPSC was blocked by 4-aminopyridine (4AP; 100 microM), a voltage-dependent potassium channel blocker, and by phospholipase A(2) inhibitors AACOCF(3) (10 microM) and quinacrine (10 microM). These results indicate that only the mu-opioid receptor is functionally present on presynaptic glutamatergic terminals in normal CeA neurons, and its activation reduces the probability of glutamate release through a signaling pathway involving phospholipase A(2) and the presynaptic, 4AP-sensitive potassium channel. This study provides evidence for the presynaptic regulation of glutamate synaptic transmission by mu-opioid receptors in CeA neurons.

4-Aminopyridine↗

PubMed2005

Soil resource availability impacts microbial response to organic carbon and inorganic nitrogen inputs.

Impacts of newly added organic carbon(C) and inorganic nitrogen (N) on the microbial utilization of soil organic matter are important in determining the future C balance of terrestrial ecosystems. We examined microbial responses to cellulose and ammonium nitrate additions in three soils with very different C and N availability. These soils included an organic soil (14.2% total organic C, with extremely high extractable N and low labile C), a forest soil (4.7% total organic C, with high labile C and extremely low extractable N), and a grassland soil (1.6% total organic C, with low extractable N and labile C). While cellulose addition alone significantly enhanced microbial respiration and biomass C and N in the organic and grassland soils, it accelerated only the microbial respiration in the highly-N limited forest soil. These results indicated that when N was not limited, C addition enhanced soil respiration by stimulating both microbial growth and their metabolic activity. New C inputs lead to elevated C release in all three soils, and the magnitude of the enhancement was higher in the organic and grassland soils than the forest soil. The addition of cellulose plus N to the forest and grassland soils initially increased the microbial biomass and respiration rates, but decreased the rates as time progressed. Compared to cellulose addition alone, cellulose plus N additions increased the total C-released in the grassland soil, but not in the forest soil. The enhancement of total C-released induced by C and N addition was less than 50% of the added-C in the forest soil after 96 d of incubation, in contrast to 87.5% and 89.0% in the organic and grassland soils. These results indicate that indigenous soil C and N availability substantially impacts the allocation of organic C for microbial biomass growth and/or respiration, potentially regulating the turnover rates of the new organic C inputs.

Analysis of Variance↗

PubMed2004

DNA immunization of mice with a plasmid encoding Neisseria gonorrhea PorB protein by intramuscular injection and epidermal particle bombardment.

Immunogenicity of a DNA vaccine encoding PorB from Neisseria gonorrhoeae strain FA1090 was analyzed in BALB/C mice immunized by intramuscular needle injection or epidermal gene gun bombardment. Both delivery routes generated measurable specific antibodies although the gene gun response was slower. Antibody isotypes were indicative of Th2 activation following gene gun immunization and of Th1 activation following intramuscular injection. In both immunization protocols, boosting with either renatured recombinant (rr) PorB protein or PorB expressed from Venezuelan equine encephalitis virus replicon particles (VRPs) significantly increased anti-PorB antibody levels. Boosting with rrPorB protein had little effect on antibody isotypes, while boosting with VRPs expressing PorB-enhanced a Th1 type response. Whole cell binding experiments showed that a portion of the antibodies recognized the surface of the homologous N. gonorrhoeae strain. Serum from groups with high antibody levels showed some opsonization of the homologous strain using human neutrophils. These results showed the potential of DNA vaccination for the purpose of priming an antibody response against PorB of N. gonorrhoeae. When combined with a protein or VRP boost, DNA priming resulted in high-titer and long-lasting responses. Based on different prime-boost protocols, we could polarize immune responses to predominantly Th1 or Th2, which should enable future studies of the types of immune responses that are protective in mouse models of gonorrhea.

Adjuvants, Immunologic↗

PubMed2004

Antiviral property and mode of action of a sulphated polysaccharide from Sargassum patens against herpes simplex virus type 2.

A sulphated polysaccharide (SP2) was isolated from the brown alga Sargassum patens. SP2 inhibited the replication of herpes simplex virus type 2 (HSV-2) dose-dependently by 38.5-96.1% of the control level, after incubations with 0.78-12.5 microg/ml of the polysaccharide. SP2 exhibited extracellular virucidal activity only in high concentrations (>/=12.5 microg/ml) but significantly inhibited the virus attachment to its host cells by 45.1%, at concentration as low as 1 microg/ml. All the results from this study suggested that the antiviral mode of action of SP2 could be ascribed to the inhibition of virus adsorption, which is different from that of the current drug of choice acyclovir.

Adsorption↗

PubMed2004

Synaptic properties and postsynaptic opioid effects in rat central amygdala neurons.

An important output of amygdaloid nuclei, the central nucleus of the amygdala (CeA) not only mediates negative emotional behaviors, but also participates in the stimulus-reward learning and expression of motivational aspects of many drugs of abuse, and links environmentally stressful conditions such as fear to endogenous pain-inhibiting mechanisms. The endogenous opioid system in the CeA is crucial for both reward behaviors and environmental stress-induced analgesia. In this study using whole-cell voltage-clamp recordings, we investigated synaptic inputs and the postsynaptic effects of opioid agonists in CeA neurons. We found that synaptic inputs evoked within the CeA were mediated by both glutamate and GABA, but those evoked from the basolateral amygdala were primarily glutamatergic. Based on membrane properties, three types of cells were characterized. Type A neurons had no spike accommodation while type B neurons displayed characteristic accommodating response. Type A neurons were further classified as either A1 or A2, based on differences in resting membrane potential and the amplitude of after-hyperpolarizing potential. micro-Opioid receptor agonists hyperpolarized a subpopulation of CeA neurons, of which the vast majority was type A1. This micro agonist-induced hyperpolarization was mediated by the opening of inwardly rectifying potassium channels. In contrast, the kappa-opioid receptor agonist hyperpolarized only type B neurons. These results illustrate three types of CeA neurons with distinctive membrane properties and differential responses to opioid agonists. They may represent functionally distinct CeA cell groups for the integration and execution of CeA outputs in the aforementioned CeA functions.

Action Potentials↗

PubMed2004

Morphine enhances nitric oxide release in the mammalian gastrointestinal tract via the micro(3) opiate receptor subtype: a hormonal role for endogenous morphine.

Studies from our laboratory have revealed a novel micro opiate receptor, micro(3), which is expressed in both human vascular tissues and leukocytes. The micro(3) receptor is selective for opiate alkaloids, insensitive to opioid peptides and is coupled to constitutive nitric oxide (cNO) release. We now identify the micro(3) receptor characteristics in mammalian gut tissues. It appears that the various regions of the mouse gut release low levels of NO (0.02 to 4.6 nM ) in a pulsatile manner. We demonstrate that morphine stimulates cNO release (peak level 17 nM) in the mouse stomach, small intestine and large intestine in a naloxone and L-NAME antagonizable manner. Opioid peptides do not exhibit cNO-stimulating capabilities in these tissues. Taken together, we surmise morphine acts as a hormone to limit gut activity via micro(3) coupled to NO release since micro opiate receptors are found in the gut and endogenous morphine is not but is found in blood.

Animals↗

PubMed2003

Nicotine inhibits voltage-dependent sodium channels and sensitizes vanilloid receptors.

Nicotine is an alkaloid that is used by large numbers of people. When taken into the body, it produces a myriad of physiological actions that occur primarily through the activation of neuronal nicotinic acetylcholine receptors (nAChRs). We have explored its ability to modulate TRPV1 receptors and voltage-gated sodium channels. The reason for investigating nicotine's effect on sodium channels is to obtain a better understanding of its anti-nociceptive properties. The reasons for investigating its effects on capsaicin-activated TRPV1 channels are to understand how it may modulate this channel that is involved in pain, inflammation, and gustatory physiology. Whole cell patch-clamp recordings from rat trigeminal ganglion (TG) nociceptors revealed that nicotine exhibited anesthetic properties by decreasing the number of evoked action potentials and by inhibiting tetrodotoxin-resistant sodium currents. This anesthetic property can be produced without the necessity of activating nAChRs. Nicotine also modulates TRPV1 receptors inducing a several-fold increase in capsaicin-activated currents in both TG neurons and in cells with heterologously expressed TRPV1 receptors. This sensitizing effect does not require the activation of nAChRs. Nicotine did not alter the threshold temperature (approximately 41 degrees C) of heat-activated currents in TG neurons that were attributed to arise from the activation of TRPV1 receptors. In this regard, its effect on TRPV1 receptors differs from those of ethanol that has been shown to increase the capsaicin-activated current but decrease the threshold temperature. These studies document several new effects of nicotine on channels involved in nociception and indicate how they may impact physiological processes involving pain and gustation.

Animals↗

PubMed2003

Involvement of the entorhinal cortex in the stress response to immobilization, but not to insulin-induced hypoglycaemia.

Although the involvement of the limbic system in the neuroendocrine responses to some stressors has been documented, the specific role of the entorhinal cortex has not been elucidated. In this study, we investigated the involvement of the entorhinal cortex in stress responses. Fos immunoreactivity, a widely used marker for neuronal activation, was detected in the entorhinal cortex of rats subjected to immobilization stress, whereas no marked staining was observed in the entorhinal cortex of the control and insulin-induced hypoglycaemia groups. Lesion of the entorhinal cortex produced by ibotenic acid significantly attenuated the adrenocorticotropic hormone (ACTH) release evoked by immobilization; however, no significant change in ACTH release was observed in insulin-induced hypoglycaemia. No significant difference between entorhinal-lesioned rats and control rats was observed in blood glucose concentrations when subjected to either immobilization or to insulin-induced hypoglycaemia. Together, these results indicate that the entorhinal cortex is closely involved in the stress response to immobilization but not to insulin-induced hypoglycaemia.

Adrenocorticotropic Hormone↗

PubMed2003

Reduced platelet adhesion on the surface of polyurethane bearing structure of sulfobetaine.

Poly(etherurethane)s are widely used as blood-contacting biomaterials due to their good biocompatibility and mechanical properties. Nevertheless, their blood compatibility is still not adequate for the more demanding applications. Surface modification is an effective way to improve the blood compatibility and retain the bulk properties of biomaterials. The purpose of present study was to design and synthesize a novel nonthrombogenic biomaterial by modifying the surface of poly(etherurethane) with zwitterionic monomer. Films of polyurethane were grafted with sulfobetaine by a three-step procedure. In the first step, the film surfaces were treated with hexamethylene diisocyanate (HDI) in toluene at 50 degrees C in the presence of di-n-butyl tin dilaurate (DBTDL) as a catalyst. The extent of the reaction was measured by ATR-IR spectra; a maximum number of free NCO group was obtained after a reaction time of 90 min. In the second step, the hydroxyl group of 4-dimethylamino-1-butanol (DMAB) was allowed to react in toluene with isocyanate groups bound on the surface. In the third step, sulfobetaine was formed on the surface through the ring-opening reaction between tertiary amine of DMAB and 1,3- propane-sultone (PS). It was characterized by ATR-IR, XPS. The data showed that the grafted surfaces were composed of sulfobetaine. The results of the contact angle measurements showed that they were strongly hydrophilic. The state of platelet adhesion and shape variation for the attached platelets was described. The modified surface shows excellent blood compatibility feature by the low platelet adhesion.

Betaine↗

PubMed2002

Proteomic analysis of nipple aspirate fluid to detect biologic markers of breast cancer.

The early detection of breast cancer is the best means to minimise disease-related mortality. Current screening techniques have limited sensitivity and specificity. Breast nipple aspirate fluid can be obtained noninvasively and contains proteins secreted from ductal and lobular epithelia. Nipple aspirate fluid proteins are breast specific and generally more concentrated than corresponding blood levels. Proteomic analysis of 1 microl of diluted nipple aspirate fluid over a 5-40 kDa range from 20 subjects with breast cancer and 13 with nondiseased breasts identified five differentially expressed proteins. The most sensitive and specific proteins were 6500 and 15 940 Da, found in 75-84% of samples from women with cancer but in only 0-9% of samples from normal women. These findings suggest that (1) differential expression of nipple aspirate fluid proteins exists between women with normal and diseased breasts, and (2) analysis of these proteins may predict the presence of breast cancer.

Adult↗