The diagnostic utility of preoperative breast magnetic resonance imaging (MRI) and/or intraoperative sub-nipple biopsy in nipple-sparing mastectomy.

BACKGROUND: The necessity of routine sub-nipple biopsy was uncertain, and the role of preoperative magnetic resonance imaging (MRI) in detecting nipple invasion in patients who have been selected for nipple sparing mastectomy (NSM) has not been adequately evaluated. METHODS: We retrospectively collected and analyzed the medical and surgical records of 434 patients with primary operable breast cancer who met the criteria for NSM and underwent breast surgery during the period January 2011 to December 2015. Patients were stratified into three risk groups (low, intermediate, and high) according to tumor size and tumor-to-nipple distance. RESULTS: Among the 434 patients in this study, 29 (6.7%) had occult invasion of the nipple-areola complex (NAC). Sub-nipple biopsy had a sensitivity of 84.6%, a specificity of 100%, a false negative rate of 1.2%, a false positive rate of 0%, and an overall accuracy rate of 98.8% in confirming NAC invasion. The NAC invasion rate was 0% in the low-risk group, 5.1% in the intermediate-risk group, and 19.7% in the high-risk group (P < 0.01). The overall NPV of preoperative MRI for predicting NAC invasion was 94.8%. Cost analysis revealed that the cost of NSM with sub-nipple biopsy was significantly higher than that of NSM alone, with a mean difference in cost of USD 238.5 (P < 0.01). CONCLUSION: The high negative predictive value of MRI for NAC invasion is useful for selection of patients receiving NSM. Sub-nipple biopsy is a reliable procedure to detect occult NAC invasion, however, routine use is not cost-effect for low risk patients.

Prognostic significance of triple negative breast cancer at tumor size 1 cm and smaller.

AIMS: The purpose of this study was to clarify the prognostic significance of triple-negative breast cancer (TNBC) with a tumor size ≤ 1 cm. MATERIALS AND METHODS: Patients with primary operable breast cancer with a tumor size ≤ 1 cm were enrolled at Changhua Christian Hospital and National Cheng-Kung University Hospital. Tumors negative for ER, PR, and HER-2 were classified as TNBCs and compared with tumors with any receptor positivity (non-TNBC) for disease-free survival (DFS) and cancer-specific survival (CSS). RESULTS: From 1995 to 2006, a total of 377 patients with tumor size ≤ 1 cm were enrolled. Compared with non-TNBC patients, TNBC patients with a tumor size ≤ 1 cm as a whole or in a lymph node-positive subgroup were not associated with a poorer 5-year DFS and CSS. In lymph node-negative patients (pT1a-bN0M0), TNBC was associated with a poorer 5-year CSS but not DFS. Compared with the hormone receptor-positive, HER-2-negative subgroup, TNBC was associated with poorer DFS and CSS. In the multivariate Cox regression hazard analysis, lymph node invasion was the most important cause of disease recurrence and cancer-specific death. CONCLUSION: TNBC is very likely an independent risk factor in small (≤1 cm) node-negative invasive breast cancer. With tumors 1 cm and smaller, lymph node invasion was the single most important prognostic factor.

Prior SO2 exposure promotes airway inflammation and subepithelial fibrosis following repeated ovalbumin challenge.

BACKGROUND: Exposure to allergens or air pollutants often leads to asthma exacerbations associated with aggravation of airway inflammation. Although, repeated allergen challenge often induces chronic allergic airway inflammation (CAAI) and airway remodelling, yet, the effects of brief exposure to air pollutants such as SO(2) on development of CAAI and airway remodelling remain to be clarified. OBJECTIVE: The aim of the experiment was to investigate the effects of acute neutrophilic airway inflammation induced by brief exposure to SO(2) on development of CAAI and subepithelial fibrosis (SEF) in a murine model of asthma. METHODS: Acute airway inflammation was induced by brief exposure to 50 p.p.m. SO(2) (1 h/d, 3 days). CAAI and SEF in BALB/c mice were induced by repeated challenge with ovalbumin (OVA) for 5 or 9 weeks with or without prior exposure to SO(2). Bronchoalveolar lavage fluid (BALF) eosinophilia as index of CAAI, BALF endothelin-1 (ET-1) and TGF-beta1 levels, morphometric evaluation of fibrotic area beneath subbasement membrane and lung hydroxyproline content (Hyp) as indexes of SEF were monitored. RESULTS: Exposure to SO(2) led to acute neutrophilic inflammation and epithelial sloughing with profound elevation of BALF ET-1. Repeated OVA challenge resulted in CAAI and SEF along with elevation of Hyp, increase of fibrotic area beneath subbasement membrane and elevation of BALF TGF-beta1. Preceding SO(2) exposure exaggerated BALF eosinophilia, facilitated and enhanced SEF with more significant elevation of BALF ET-1 and TGF-beta1 levels compared with OVA-challenged mice without prior exposure to SO(2). The increase of Hyp was positively correlated with elevation of BALF TGF-beta1 during CAAI (r=0.842, P<0.01). CONCLUSION: This data demonstrated that SEF developed in parallel with severity and time course of CAAI following repeated OVA challenge. SO(2)-induced acute epithelial injury and neutrophilic inflammation could enhance CAAI and promote SEF, probably through overexpression of ET-1 and TGF-beta1.

Chromatographic identification of a biochemical alteration in the aqueous humour of megalophthalmic Black Moor goldfish.

PURPOSE: To observe if any biochemical abnormalities exist between the eye of megalophthalmic and non-megalophthalmic goldfish by high-performance liquid chromatography (HPLC). METHOD: Aqueous humour and sera from megalophthalmic and non-megalophthalmic goldfish were subjected to HPLC and monitored by photodiode array detection (Waters, MA, USA). RESULTS: An unusual accumulation of a compound with a UV absorption maximum at 290 nm was observed in the aqueous humour of megalophthalmic eye. This compound was also present in the sera of both normal goldfish and one of its megalophthalmic mutant. However, it was significantly elevated in the aqueous humour of the megalophthalmic eye only. This compound concentration was very high in the eye of small fish and its concentration increased only slightly with the expansion of the eye in larger fish. CONCLUSIONS: The presence of this compound in the serum and aqueous humour indicates a specific systemic metabolic variation in Black Moor goldfish not seen other animal species we had studied (humans, bovine, chick, rabbits and rats). The marked elevation of this compound in the megalophthalmic eye indicates a possible association of this compound with the metabolic variation accounting for the expansion of the eye in megalophthalmic goldfish.

Nitric oxide synthase neurons in different areas of normal aged and Alzheimer's brains.

This study investigated the distribution of nitric oxide synthase-containing neurons in the cerebral cortex of individuals with Alzheimer's disease, and compared them with age-matched controls. Paraffin-embedded sections of the frontal (area 10), occipital (area 17) and entorhinal cortices (area 28), and hippocampal formation obtained from 13 autopsy cases were used in the study. Neurons expressing nitric oxide synthase messenger RNA and protein were identified, respectively, by in situ hybridization and immunohistochemistry. Optical densities of nitric oxide synthase-positive neurons were assessed in 50 randomly selected fields of each of the above regions of the cortices, in each case by microscopic photometry. In the frontal cortex of the Alzheimer group, while a decrease in the number of nitric oxide synthase-positive neurons was evident, the nitric oxide synthase neurons, on the other hand, showed an increased optical density in layers II-IV when compared with those of normal ageing. In the occipital cortices, no significant differences in optical density were recorded between the normal ageing and Alzheimer specimens. In the entorhinal cortex, the optical densities of nitric oxide synthase neurons were again similar between the Alzheimer and age-matched control groups. In the hippocampar formation itself, there was an increase of nitric oxide synthase staining in the Alzheimer patients. These results show that (i) nitric oxide synthase neurons are abundant in the human cortex, (ii) the distribution of nitric oxide synthase neurons differs between different cortical regions, and (iii) there are differences between normal ageing and Alzheimer patients in the frontal cortex and the hippocampus.

Neurotransmitters, peptides, and neural cell adhesion molecules in the cortices of normal elderly humans and Alzheimer patients: a comparison.

Immunocytochemical techniques was used to compare the proportion of neurons expressing various neurotransmitters (tyrosine hydroxylase, choline acetyltransferase and gamma-aminobutyric acid), neuropeptides (Leu-enkephalin and substance P) and neural cell adhesion molecules (NCAM) in the hippocampus, frontal (area 10) and occipital (area 17) cortices of neurologically normal elderly humans to that of age-matched Alzheimer disease (AD) patients. There was no difference in the proportion of GABAergic and cholinergic cells between the normal and AD groups in all three brain regions studied. However, the catecholaminergic cells in the frontal cortex of the AD patients revealed a significant decrease. The catecholaminergic cells present in the cortex were both neurons and astrocytes, as revealed by a double immunostaining of tyrosine hydroxylase and glial fibrillary acid protein (GFAP). Furthermore, the difference in the proportion of cells expressing Substance P and Leu-enkephalin was minimal between the two groups studied. Although there was little difference in the levels of NCAM in the occipital cortex and hippocampus of the two groups, there were significantly fewer positive NCAM neurons in the frontal cortex of AD than normal aging individuals.

Terminal dUTP nick end labeling (TUNEL) positive cells in the different regions of the brain in normal aging and Alzheimer patients.

This study investigated terminal dUTP nick-end labeling (TUNEL)-positive cells in the frontal, occipital, and hippocampal cortices of seven normal aging and four Alzheimer's patients. Significant increase in TUNEL-positive cells was observed in the frontal and hippocampal cortices of Alzheimer's patients when compared with controls. In the hippocampal cortex, only area CA4 demonstrated a significant increase of TUNEL-positive cells. Double staining of TUNEL-positive cells for glial fibrillary acidic protein revealed that < 13% of the TUNEL-positive nuclei belonged to astrocytes. The results of this study illustrated a differential pattern of cortical degeneration between normal aging and Alzheimer patients.

Somatostatin-positive neurons in the different parts of the brain in normal aging and Alzheimer's disease.

The present work seeks to verify if there is a difference in the number of somatostatin neurons in the cortex between normal aging versus Alzheimer patients and secondly if any of these neurons are dying via apoptosis. In our specimens, immuno-histochemistry revealed that there was no difference in the number of somatostatin neurons between the two study groups. Moreover, of the apoptotic cells that were found using the terminal dUTP nick end labeling (TUNEL) method, none contained somatostatin. It is concluded that while there is apoptotic cell death in normal aging and Alzheimer's disease, it does not seem to occur in neurons which contain somatostatin in any significant amount.

Differential coupling of the formyl peptide receptor to adenylate cyclase and phospholipase C by the pertussis toxin-insensitive Gz protein.

In neutrophils, activation of receptors for the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP) leads to changes in intracellular events such as phosphoinositide turnover and Ca2+ mobilization. Studies have shown that activation of the cloned fMLP receptor can also lead to inhibition of cyclic AMP (cAMP) accumulation [Lang, Boulay, Li and Wollheim (1993) EMBO J. 12, 2671-2679; Uhing, Gettys, Tomhave, Snyderman and Didsbury (1992) Biochem. Biophys. Res. Commun. 183, 1033-1039]. These responses are apparently mediated through pertussis toxin-sensitive Gi proteins. Since other chemotactic factor receptors can couple to multiple G proteins, we examined the ability of the fMLP receptor to utilize a pertussis toxin-insensitive G protein, Gz, in its signal transduction pathways. The human fMLP receptor was transiently expressed in 293 and Ltk- cells, and subsequently assayed for receptor-mediated inhibition of cAMP accumulation and stimulation of phosphoinositide-specific phospholipase C. In transfected 293 cells, fMLP inhibited choriogonadotropin-stimulated cAMP accumulation by 50% and the response could be abolished by pertussis toxin. Co-expression of the fMLP receptor with the alpha subunit of Gz rendered the fMLP response pertussis toxin-insensitive, indicating that the endogenous Gi proteins can be substituted efficiently by Gz. In contrast, Ltk- cells expressing the fMLP receptor were able to respond to fMLP with an increase in the production of inositol phosphates, but this response was completely abolished by pertussis toxin even in cells co-expressing the alpha subunit of Gz. Thus, although both signalling pathways appeared to utilize Gi-like proteins, Gz can only replace Gi in mediating inhibition of cAMP accumulation, and not in the stimulation of phospholipase C. Differential interaction with Gz might represent a novel mechanism by which fMLP receptors regulate intracellular events.

Gz coupling to the rat kappa-opioid receptor.

We have expressed the cloned rat kappa-opioid receptor in human embryonic kidney 293 cells and studied the ability of kappa-selective ligands to inhibit adenylyl cyclase. In transfected 293 cells, activation of the kappa-opioid receptor by U50,488 and the dynorphins resulted in the inhibition of cAMP accumulation. The inhibitory response was sensitive to pertussis toxin and highly selective for kappa-agonists; neither mu- nor delta-opioids were able to activate the kappa-opioid receptor. Upon co-transfection with the alpha subunit of Gz, inhibition of cAMP accumulation by kappa-agonist became refractory to pertussis toxin, indicating that the kappa-opioid receptor can couple to both G(i) and Gz proteins.

An evaluation of leucocyte analysis on the Coulter STKS.

The performance of leucocyte analysis on the Coulter STKS (Coulter, Hialeah, FL, USA) was evaluated for accuracy, precision and reliability. The results were compared with those obtained from visual examination of a Romanowsky stained blood film together with the automated WBC-diff. from the Technicon H*1 (Technicon, Tarrytown, NY, USA). The relationship between the number of cells counted per WBC-diff. and the WBC count of the sample was established. Precision of the STKS WBC-diff. was acceptable on blood samples with normal and low WBC counts. Correlation with an 800 cell manual WBC-diff. (n = 104) was excellent (r = 0.97, 0.97, 0.83, 0.98 and 0.53 for neutrophils, lymphocytes, monocytes, eosinophils and basophils respectively). Blood specimens, collected into dipotassium EDTA, could be stored at 20-25 degrees C for at least 8 h with no significant effect on the STKS WBC-diff. In a study of 513 patient samples, the BLASTS suspect flag gave 5.4% false positives and zero false negatives, the VARIANT LYMPHS flag gave 1.5% false positives and 0.4% false negatives, and the IMM GRANS/BANDS flag gave 30.8% false positives and 2.3% false negatives. Several instrument and sample related problems were encountered during this study. Despite these limitations, the STKS can provide efficient 5 part WBC-diffs. and effective screening for WBC abnormalities.