Allergen-specific IgE: comparison between skin prick test and serum assay in real life.

BACKGROUND: The most common sensitizing allergens in in the area of Liguria region (Northwestern Italy) are pollens, mainly Parietaria and cypress, house dust mites, i.e. Dermatophagoides, and pets. IgE assessment is a crucial step in allergy diagnosis. It may be performed by skin prick test (SPT) or serum IgE (sIgE) assay. Therefore, this study compared these two methods in a real-life setting. METHODS: This retrospective study included 793 subjects, who were referred to the Allergy Department for respiratory allergy during 2014. Inclusion criteria were i) documented diagnosis of allergic rhinitis (AR), and/or allergic asthma, and/or allergic conjunctivitis. SPT and sIgE assay were performed for 5 allergens, such as Dermatophagoides pteronyssinus (D1), cat (E1), Parietaria officinalis (W19), cypress (T23), and dog (E5), as they are the most common in our geographic area. RESULTS: Using a positive SPT result as the target condition, remarkably high and statistically significant values of AUC, ranging from 0.84 to 0.94, were found. On the basis of the Youden index the following optimal classification threshold values were also computed: D1 = 0.22, E1 = 0.26, W19 = 0.61, T23 = 0.25, E5 = 0.34. These values allowed to define a set of sensitivity/specifity estimates ranging from 0.75 to 0.93 and from 0.83 to 0.93, respectively. CONCLUSIONS: The present study shows that SPT and sIgE are two tests that are rather concordant, but with different sensitivity and specificity distinct for each allergen. In clinical practice, both tests should be used depending on clinical history features and obtained findings.

Highlighting the 'blood-nerve barrier' in virology research.

The blood-nerve barrier (BNB) shields peripheral nerves from the blood in order to maintain the homeostasis of the nervous system. In the field of infectious diseases, little information is currently available concerning the BNB. Recently documented evidence in virology suggests that elevated permeability of the BNB by immune cells and the natural absence of the BNB in the olfactory mucosa play significant roles in neuroprotection as well as neuropathogenesis. Importantly, the BNB can behave more flexibly than previously thought. In the near future, drug delivery via manipulation of the BNB will shed light on new therapeutic and prophylactic strategies for serious and intractable nervous system infections.

A glial K(+) /Cl(-) cotransporter modifies temperature-evoked dynamics in Caenorhabditis elegans sensory neurons.

K(+) /Cl(-) cotransporters (KCCs) are known to be crucial in the control of neuronal electrochemical Cl(-) gradient. However, the role of these proteins in glial cells remains largely unexplored despite a number of studies showing expression of KCC proteins in glial cells of many species. Here, we show that the Caenorhabditis elegans K(+) /Cl(-) cotransporter KCC-3 is expressed in glial-like cells and regulates the thermosensory behavior through modifying temperature-evoked activity of a thermosensory neuron. Mutations in the kcc-3 gene were isolated from a genetic screen for mutants defective in thermotaxis. KCC-3 is expressed and functions in the amphid sheath glia that ensheathes the AFD neuron, a major thermosensory neuron known to be required for thermotaxis. A genetic analysis indicated that the regulation of the thermosensory behavior by KCC-3 is mediated through AFD, and we further show that KCC-3 in the amphid sheath glia regulates the dynamics of the AFD activity. Our results show a novel mechanism by which the glial KCC-3 protein non-cell autonomously modifies the stimulus-evoked activity of a sensory neuron and highlights the functional importance of glial KCC proteins in modulating the dynamics of a neural circuitry to control an animal behavior.

Transolfactory neuroinvasion by viruses threatens the human brain.

Viral neuroinvasion via the olfactory system has been investigated in a variety of virus-animal models by scientists in many fields including virologists, pathologists, and neurologists. In humans, herpes simplex virus type 1 (HSV-1), human herpesvirus 6 (HHV-6), Borna disease virus, rabies virus, and influenza A virus have been shown to take the olfactory route for neuroinvasion based on forensic and post-mortem specimens. This article briefly summarizes the anatomy, physiology, and immunology of the olfactory system and presents a battery of neurovirulent viruses that may threaten the human brain by invading through this peripheral pathway, especially focusing on two of the most intensively studied viruses--HSV-1 and influenza A virus. Viruses may insidiously invade the olfactory neural network not only to precipitate encephalitis/encephalopathy but also to promote the development of neurodegenerative and demyelinating disorders. Substantial information obtained by analyzing human specimens is required to argue for or against this hypothesis.

Two guard cell mitogen-activated protein kinases, MPK9 and MPK12, function in methyl jasmonate-induced stomatal closure in Arabidopsis thaliana.

Methyl jasmonate (MeJA) and abscisic acid (ABA) signalling cascades share several signalling components in guard cells. We previously showed that two guard cell-preferential mitogen-activated protein kinases (MAPKs), MPK9 and MPK12, positively regulate ABA signalling in Arabidopsis thaliana. In this study, we examined whether these two MAP kinases function in MeJA signalling using genetic mutants for MPK9 and MPK12 combined with a pharmacological approach. MeJA induced stomatal closure in mpk9-1 and mpk12-1 single mutants as well as wild-type plants, but not in mpk9-1 mpk12-1 double mutants. Consistently, the MAPKK inhibitor PD98059 inhibited the MeJA-induced stomatal closure in wild-type plants. MeJA elicited reactive oxygen species (ROS) production and cytosolic alkalisation in guard cells of the mpk9-1, mpk12-1 and mpk9-1 mpk12-1 mutants, as well in wild-type plants. Furthermore, MeJA triggered elevation of cytosolic Ca(2+) concentration ([Ca(2+)]cyt ) in the mpk9-1 mpk12-1 double mutant as well as wild-type plants. Activation of S-type anion channels by MeJA was impaired in mpk9-1 mpk12-1. Together, these results indicate that MPK9 and MPK12 function upstream of S-type anion channel activation and downstream of ROS production, cytosolic alkalisation and [Ca(2+)]cyt elevation in guard cell MeJA signalling, suggesting that MPK9 and MPK12 are key regulators mediating both ABA and MeJA signalling in guard cells.

Cyclic adenosine 5'-diphosphoribose (cADPR) cyclic guanosine 3',5'-monophosphate positively function in Ca(2+) elevation in methyl jasmonate-induced stomatal closure, cADPR is required for methyl jasmonate-induced ROS accumulation NO production in guard cells.

Methyl jasmonate (MeJA) signalling shares several signal components with abscisic acid (ABA) signalling in guard cells. Cyclic adenosine 5'-diphosphoribose (cADPR) and cyclic guanosine 3',5'-monophosphate (cGMP) are second messengers in ABA-induced stomatal closure. In order to clarify involvement of cADPR and cGMP in MeJA-induced stomatal closure in Arabidopsis thaliana (Col-0), we investigated effects of an inhibitor of cADPR synthesis, nicotinamide (NA), and an inhibitor of cGMP synthesis, LY83583 (LY, 6-anilino-5,8-quinolinedione), on MeJA-induced stomatal closure. Treatment with NA and LY inhibited MeJA-induced stomatal closure. NA inhibited MeJA-induced reactive oxygen species (ROS) accumulation and nitric oxide (NO) production in guard cells. NA and LY suppressed transient elevations elicited by MeJA in cytosolic free Ca(2+) concentration ([Ca(2+)]cyt) in guard cells. These results suggest that cADPR and cGMP positively function in [Ca(2+)]cyt elevation in MeJA-induced stomatal closure, are signalling components shared with ABA-induced stomatal closure in Arabidopsis, and that cADPR is required for MeJA-induced ROS accumulation and NO production in Arabidopsis guard cells.

TAK-875, a GPR40/FFAR1 agonist, in combination with metformin prevents progression of diabetes and ß-cell dysfunction in Zucker diabetic fatty rats.

BACKGROUND AND PURPOSE: TAK-875, a selective GPCR40/free fatty acid receptor 1 agonist, improves glycaemic control by increasing glucose-dependent insulin secretion. Metformin is a first-line drug for treatment of type 2 diabetes that improves peripheral insulin resistance. Based on complementary mechanism of action, combining these agents is expected to enhance glycaemic control. Here, we evaluated the chronic effects of TAK-875 monotherapy and combination therapy with metformin in diabetic rats. EXPERIMENTAL APPROACH: Long-term effects on glycaemic control and ß-cell function were evaluated using Zucker diabetic fatty (ZDF) rats, which develop diabetes with hyperlipidaemia and progressive ß-cell dysfunction. KEY RESULTS: Single doses of TAK-875 (3-10 mg·kg(-1) ) and metformin (50-150 mg·kg(-1) ) significantly improved both postprandial and fasting hyperglycaemia, and additive improvements were observed in their combination. Six-week treatment with TAK-875 (10 mg·kg(-1) , b.i.d.) significantly decreased glycosylated Hb (GHb) by 1.7%, and the effect was additively enhanced by combination with metformin (50 mg·kg(-1) , q.d.; GHb: -2.4%). This improvement in glycaemic control in the combination group was accompanied by significant 3.2-fold increase in fasting plasma insulin levels. Pancreatic insulin content was maintained at a level comparable to that in normal rats by combination treatment (vehicle: 26, combination: 67.1; normal lean: 69.1 ng·mg(-1) pancreas) without affecting pancreatic glucagon content. Immunohistochemical analyses revealed normal morphology, enhanced pancreas duodenum homeobox-1 expression and increased PCNA-positive cells in islets of the combination group. CONCLUSION AND IMPLICATIONS: Our results indicate that combination therapy with TAK-875 and metformin could be a valuable strategy for glycaemic control and ß-cell preservation in type 2 diabetes.

Two guard cell-preferential MAPKs, MPK9 and MPK12, regulate YEL signalling in Arabidopsis guard cells.

We report that two mitogen-activated protein kinases (MAPKs), MPK9 and MPK12, positively regulate abscisic acid (ABA)-induced stomatal closure in Arabidopsis thaliana. Yeast elicitor (YEL) induced stomatal closure accompanied by intracellular reactive oxygen species (ROS) accumulation and cytosolic free calcium concentration ([Ca(2+) ]cyt ) oscillation. In this study, we examined whether these two MAP kinases are involved in YEL-induced stomatal closure using MAPKK inhibitors, PD98059 and U0126, and MAPK mutants, mpk9, mpk12 and mpk9 mpk12. Both PD98059 and U0126 inhibited YEL-induced stomatal closure. YEL induced stomatal closure in the mpk9 and mpk12 mutants but not in the mpk9 mpk12 mutant, suggesting that a MAPK cascade involving MPK9 and MPK12 functions in guard cell YEL signalling. However, YEL induced extracellular ROS production, intracellular ROS accumulation and cytosolic alkalisation in the mpk9, mpk12 and mpk9 mpk12 mutants. YEL induced [Ca(2+) ]cyt oscillations in both wild type and mpk9 mpk12 mutant. These results suggest that MPK9 and MPK12 function redundantly downstream of extracellular ROS production, intracellular ROS accumulation, cytosolic alkalisation and [Ca(2+) ]cyt oscillation in YEL-induced stomatal closure in Arabidopsis guard cells and are shared with ABA signalling.

Ecotoxicological characterization of tannery wastewater in Dhaka, Bangladesh.

Tanning industries are one of the main economic activities in Bangladesh. It has been well documented that wastewater discharged from tanneries without appropriate treatment results in detrimental effects on the ecosystem. No ecotoxicity evaluation of any aquatic environment in Bangladesh has been conducted so far. In this study a battery of toxicity bioassays and chemical analysis were carried out from water samples obtained from three sampling points: upstream from discharging site on River Buriganga (S1), raw wastewater effluent (S2), and downstream the discharging sluice gate (S3), in the Hazaribagh tannery area of Dhaka City, Bangladesh. While S1 and S3 water samples did not show significant toxicity in the bioassays tested, S2 exhibited high acute toxicity to the bacterium Vibrio fischeri (15-min Microtox test, EC50 = 9.8%), the higher plant Lactuca sativa (5-day root elongation inhibition test, EC50 = 14.2%), and the microcrustacean Daphnia magna (24-hour mobility test, EC50 = 31.5%). The results suggested that the raw wastewater effluent had detrimental effects on broad spectrum of organisms in the aquatic ecosystem and bacterium was the most sensitive. The chemical analysis revealed that sample S2 contained an extremely high concentration of chromium (47 g l(-1)). Additionally microbiological analysis indicated that the sampling area is impacted by fecal pollution, increasing the environmental health risk for its inhabitants.

Distinct thermal migration behaviors in response to different thermal gradients in Caenorhabditis elegans.

The nematode Caenorhabditis elegans exhibits a complex behavior called thermotaxis in response to temperature. This behavior is defined as a form of associative learning, in which temperature pairs with the presence or absence of food. Different interpretations have been drawn from the diverse results obtained by several groups, mainly because of the application of different methodologies for the analysis of thermotaxis. To clarify the discrepancies in behavioral observations and subsequent interpretations by different laboratories, we attempted to systematize several parameters to observe thermotaxis behavior as originally defined by Hedgecock and Russell in 1975. In this study, we show clearly how C. elegans can show a conditioned migration toward colder or warmer areas on a thermal gradient, given certain criteria necessary for the observation of thermotaxis. We thus propose to distinguish thermotaxis from other temperature-related behaviors, such as the warm avoidance response displayed at temperature gradients of 1 degrees C/cm and steeper.

Effect of radiation monitoring method and formula differences on estimated physician dose during percutaneous coronary intervention.

BACKGROUND: Currently, one or two dosimeters are used to monitor radiation exposure in most cardiac laboratories. In addition, several different formulas are used to convert exposure data into an effective dose (ED). PURPOSE: To clarify the effect of monitoring methods and formula selection on the estimated ED for physicians during percutaneous coronary interventions (PCIs). MATERIAL AND METHODS: The ED of physicians during cardiac catheterization was determined using an optically stimulated luminescence dosimeter (Luxel badge). Two Luxel badges were worn: one beneath a personal lead apron (0.35-mm lead equivalent) at the chest and one outside of the apron at the neck. RESULTS: The difference in the average ED of seven physicians was approximately fivefold (range 1.13-5.43 mSv/year) using the six different formulas in the clinical evaluation. The estimated physician ED differed markedly according to both the monitoring method and formula selected. CONCLUSION: ED estimation is dependent on both the monitoring method and the formula used. Therefore, it is important that comparisons among laboratories are based on the same monitoring method and same formula for calculating the ED.

Antialiasing backprojection for helical MDCT.

Helical CTs are well known to suffer from aliasing artifacts because of their finite longitudinal sampling pitch. The artifact pattern is typically strong streaks from bone edges in clinical images. Especially in the case of multidetector row CT, the artifact resulting from longitudinal aliasing is often called a windmill artifact because the visible streaks form a windmill pattern when the object is of a particular shape. The scan must be performed using a very thin slice thickness, i.e., fine sampling in the longitudinal direction, with a longer scan time to mitigate this aliasing artifact. Some elaborate longitudinal interpolation methods to remediate longitudinal aliasing have been proposed, but they have not been successful in practice despite their theoretical importance. A periodic swing of the focal spot in the longitudinal direction, a so-called z-flying focal spot, was introduced recently to achieve finer sampling. Although it is a useful technique, some important deficiencies exist: It is sufficiently effective only near the isocenter and is difficult to apply to a scan using a thick slice thickness, even though longitudinal aliasing is more serious at the thicker scan. In this paper, the author addresses the nature of interlaced (or unequally spaced) sampling and derives a new principle of data treatment that can suppress the aliased spectra selectively. According to this principle, the common practice of image reconstruction, which backprojects data along the original sampling ray path, is never the best choice. The author proposes a new scheme of backprojection, which involves the longitudinal shift of projection data. A proper choice of longitudinal shift for backprojection provides effective and selective suppression of aliased spectra, with retention of the original frequency spectrum depending on the level of focus swing. With this shifted backprojection, the swing of focus can be made much smaller than for a conventional z-flying focal spot. The required amount of shift for backprojection is position dependent. Nevertheless, its implementation in the reconstruction process can be achieved simply by relocating the x-ray source and detector assembly from positions of actual scanning. Through simulation, the combination of shifted backprojection and the small swing of focus is evaluated. Results confirm that the artifact attributable to longitudinal aliasing is well suppressed in the entire field of view, whereas the penalty on the slice sensitivity profile (or longitudinal resolution) can be kept minimal. Moreover, this method solves other deficiencies of z-flying focus, such as inapplicability to scans with a thicker slice thickness.

The mechanism of development of acute lung injury in lethal endotoxic shock using alpha-galactosylceramide sensitization.

The mechanism underlying acute lung injury in lethal endotoxic shock induced by administration of lipopolysaccharide (LPS) into alpha-galactosylceramide (alpha-GalCer)-sensitized mice was studied. Sensitization with alpha-GalCer resulted in the increase of natural killer T (NK T) cells and the production of interferon (IFN)-gamma in the lung. The IFN-gamma that was produced induced expression of adhesion molecules, especially vascular cell adhesion molecule-1 (VCAM-1), on vascular endothelial cells in the lung. Anti-IFN-gamma antibody inhibited significantly the VCAM-1 expression in alpha-GalCer-sensitized mice. Very late activating antigen-4-positive cells, as the counterpart of VCAM-1, accumulated in the lung. Anti-VCAM-1 antibody prevented LPS-mediated lethal shock in alpha-GalCer-sensitized mice. The administration of LPS into alpha-GalCer-sensitized mice caused local production of excessive proinflammatory mediators, such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and nitric oxide. LPS caused microvascular leakage of proteins and cells into bronchoalveolar lavage fluid. Taken together, sensitization with alpha-GalCer was suggested to induce the expression of VCAM-1 via IFN-gamma produced by NK T cells and recruit a number of inflammatory cells into the lung. Further, LPS was suggested to lead to the production of excessive proinflammatory mediators, the elevation of pulmonary permeability and cell death. The putative mechanism of acute lung injury in LPS-mediated lethal shock using alpha-GalCer sensitization is discussed.

The effects of microbial materials adhered to Asian sand dust on allergic lung inflammation.

Asian sand dust (ASD) containing microbiological materials, sulfate (SO(4)(2)), and nitrate (NO(3)(-) ) derived from air pollutants in East China, reportedly cause adverse respiratory health effects. ASD aggravates ovalbumin (OVA)-associated experimental lung eosinophilia. In this study, the toxic materials adsorbed onto ASD were excluded by heat treatment at 360 degrees C for 30 min. The effects of nonheated ASD or heated ASD (H-ASD) toward the allergic lung inflammation were compared in murine lungs. ICR mice were administered intratracheally with normal saline (control), H-ASD, ASD, OVA, OVA + H-ASD, and OVA + ASD, four times at 2-week intervals. ASD only increased neutrophils in bronchoalveolar lavage fluids (BALFs) along with pro-inflammatory mediators, such as keratinocyte chemoattractant (KC). H-ASD and ASD enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. The two ASDs synergistically increased interleukin-5 (IL-5), monocyte chemotactic protein-3 (MCP-3), and eotaxin, which were associated with OVA, in BALF. The enhancing effects were much greater in ASD than in H-ASD. The two ASDs induced the adjuvant effects to specific IgE and IgG1 production by OVA. In the in vitro study using RAW264.7 cells, ASD increased the expression of Toll-like receptor 2 (TLR 2) mRNA but not TLR4 mRNA. H-ASD caused no expression of either TLR mRNA. These results suggest that the aggravated lung eosinophilia by ASD may be due to activation of Th2-associated immune response via the activation of TLR2 by microbial components adhered to ASD.

Lipopolysaccharide augments the in vivo lethal action of doxorubicin against mice via hepatic damage.

The effect of lipopolysaccharide (LPS) on the in vivo lethal action of doxorubicin (DOX) against mice was studied. DOX killed LPS-pretreated mice much earlier than untreated mice, and exhibited a stronger toxic action against LPS-pretreated mice. DOX-induced lethality in LPS-pretreated mice was due to severe hepatic damage, but there were no significant lesions in the heart, kidney and lung. Hepatic lesions were accompanied by caspase 3-positive cells and fragmented DNA-positive cells, suggesting the involvement of apoptosis. DOX induced the production of a high level of interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in LPS-pretreated mice, but not in non-treated mice. The DOX-induced lethality was prevented significantly by anti-IFN-gamma antibody, but not anti-TNF-alpha antibody. Administration of recombinant IFN-gamma in place of LPS augmented definitively the DOX-induced lethality. LPS augmented the DOX-induced lethality in TNF-alpha-deficient mice. Taken together, LPS was suggested to enhance DOX-induced IFN-gamma production and augment the in vivo lethal action via hepatic damage.

Lipopolysaccharide and interferon-gamma enhance Fas-mediated cell death in mouse vascular endothelial cells via augmentation of Fas expression.

The effect of interferon (IFN)-gamma and/or lipopolysaccharide (LPS) on Fas-mediated cell death with anti-Fas agonistic antibody in vascular endothelial cells was examined using a mouse END-D cell line. Anti-Fas agonistic antibody exhibited cytotoxic actions on END-D cells. Fas-mediated cell death was enhanced by LPS or IFN-gamma. The combination of IFN-gamma and LPS significantly enhanced cell death compared to IFN-gamma or LPS alone. IFN-gamma and LPS augmented cell surface expression of Fas, but not tumour necrosis factor (TNF) receptor 1. Inhibitors of p38 mitogen-activated protein kinase (MAPK) prevented augmentation of Fas expression in IFN-gamma and LPS-treated END-D cells. IFN-gamma and LPS-treated END-D cells did not become susceptible to TNF-alpha or nitric oxide-mediated cytotoxicity. IFN-gamma and LPS thus appear to augment selectively Fas expression via activation of p38 MAPK and enhance Fas-mediated cell death in END-D cells. Furthermore, administration of IFN-gamma and LPS into mice induced in vivo expression of Fas on vascular endothelial cells and Fas ligand (FasL) on peripheral blood leucocytes. The relationship between enhancement of Fas-mediated cell death by IFN-gamma and LPS and the development of vascular endothelial injury is discussed.

The preventive effect of Daikenchuto on postoperative adhesion-induced intestinal obstruction in rats.

The present study investigated the effect of Daikenchuto (DKT) on postoperative intestinal adhesion in rats. We evaluated the effects of DKT, constituent medical herbs and active compounds on talc-induced intestinal adhesion in rats and DKT-induced contractions using isolated guinea pig ileum. DKT significantly prevented adhesion formation, and this action was inhibited by pretreatment with atropine or ruthenium red. The constituent medical herbs, Zanthoxylum Fruit and Maltose Syrup Powder significantly prevented adhesion formation. Moreover, hydroxy sanshool (HS) prevented adhesion formation, and this action was inhibited by pretreatment with ruthenium red. In contrast, DKT-induced contractions were inhibited by tetrodotoxin, atropine, and capsazepine. These results suggested that DKT had a preventive action on postoperative adhesive intestinal obstruction, and that this action was mediated by sensory and cholinergic nerves. Furthermore, HS was found to be one of the active compound of DKT, and its action was mediated by sensory nerves.

Quality of life and psychological well-being in GH-treated, adult PWS patients: a longitudinal study.

BACKGROUND: Prader-Willi syndrome (PWS) is a congenital alteration of chromosome pair 15. It is characterized by short stature, muscular hypotonia, hyperphagia, obesity, behavioural and emotional disturbances, hypogonadism and partial Growth Hormone (GH) deficiency. The aim of this study was to assess the long-term effect of GH treatment on the psychological well-being and Quality of Life (QoL) in an adult PWS group. METHODS: A total of 13 PWS patients, their diagnosis confirmed by genetic tests, and their parents were recruited for this study. The participants were administered the 36-Items Short Form Health Survey (SF-36) and the Psychological General Well-Being Index (PGWBI), for the assessment of QoL and psychological well-being, at the beginning of GH treatment, and at following intervals of 6, 12 and 24 months. Modified versions of the same questionnaires were given to the parents. RESULTS: Significant improvement with respect to the baseline was found, on both scales, in the evaluation of both physical and psychological well-being, although the parents' evaluation was less optimistic than that of the patients. CONCLUSION: Our findings suggest that the amelioration of QoL and psychological status is sustained in patients who continue GH treatment.

Mastopathic fibroadenoma of the breast: a pitfall of aspiration cytology.

OBJECTIVE: To assess the correlation between cytological diagnoses and histological subtypes of fibroadenoma (FA) and to clarify the cytological features of a specific group of FA displaying variable features similar to fibrocystic disease (mastopathic type, MFA), and to evaluate the significance of this subtype in cytological diagnosis. METHODS: A review of 141 cases of histologically proven FA was performed. We re-classified them into four subtypes according to Kinoshita's criteria [Jpn J Breast Cancer6 (1991) 377] and further selected 92 cases for which both fine needle aspiration (FNA) smears and histological specimens were available. Among them, 18 cases of MFA and their cytological smears were selected for the present study. RESULTS: There was significant correlation between MFA and cytological diagnosis of 'indeterminate' or 'suspicious for malignancy' (P < 0.01). Although no false-positive diagnosis was experienced in our series, 56% of the MFAs (10/18) had cytological diagnoses of indeterminate or were included in the category 'suspicious for malignancy'. Smears from MFA revealed high cellularity (9/18 smears had more than 10 epithelial clusters each composed of more than 50 cells), presence of cellular discohesiveness (13/18, 72.2%), but only mild nuclear atypia (5/18, 27.8%). Anisonucleosis was present in fewer than half the cases and no apparent condensed chromatin was identified. CONCLUSION: We highlight the significance of subclassification of MFA in aspiration cytology of breast. MFA had a significantly higher chance of falling into the 'suspicious for malignancy' or 'indeterminate' diagnostic category in aspiration cytology. It might be a diagnostic challenge for cytopathologist to identify this subtype of FA in FNA smears.