Insensitive Research Articles

Prediction model of the response to neoadjuvant chemotherapy in breast cancers by a Naive Bayes algorithm

Background and Objective:Chemotherapy is useful to many breast cancer patients, however, it is not therapeutic for some patients. Pathologic complete response (pCR) is an indicator to good response in Neoadjuvant chemotherapy (NAC). In this study, we aimed to develop a way to predict pCR before NAC. Methods:We retrospectively collected 287 stage II-III breast cancer cases either to a training set (N = 197) or to a test set (N = 90). Fourteen candidate genes were selected from four public microarray data sets. A prediction model was built, by using these fourteen candidate genes and three reference genes expression which were tested by TaqMan probe-based quantitative polymerase chain reaction, after selecting a better algorithm. Results:The Naive Bayes algorithm had a relatively higher predictive value, compared with random forest, support vector machine (SVM), and k-nearest neighbor (knn) algorithms (P < 0.05). This 17-gene prediction model showed a high positive correlation with pCR (odds ratio, 8.914, 95% confidence interval, 4.430–17.934, P < 0.001). By using this model, the enrolled patients were classified into sensitive (SE) and insensitive (INS) groups. The pCR rates between the SE and INS groups were highly different (42.3% vs.7.6%, P < 0.001). The sensitivity and specificity of this prediction model were 84.5% and 62.0%. Conclusions:Instead of whole transcriptome-based technologies, panel gene expression with tens of essential genes implemented in a machine learning model has predictive potential for chemosensitivity in breast cancers.

Acceptability of entire male pork with various levels of androstenone and skatole by consumers according to their sensitivity to androstenone

Consumer acceptability of entire male pork at eating was assessed in three experiments. The 140 consumers involved in each experiment were classified as insensitive (INSENS) to the odor of pure androstenone or sensitive perceiving it as pleasant (SENS-PLEA) or unpleasant (SENS-UNPL). Entire male pork with very low skatole and androstenone levels (LS-LA) was as well accepted as gilt pork, whatever the consumer category. Entire male pork with elevated levels in both skatole and androstenone (HS-HA) was clearly differentiated from LS-LA pork by SENS-UNPL, but not by SENS-PLEA or INSENS consumers. Whatever the consumer category, entire male pork with elevated levels of androstenone and very low levels of skatole (LS-HA and LS-HHA) were not significantly differentiated from LS-LA pork. The results suggest that, in the conditions of the present experiment, androstenone and skatole totally explain boar taint at eating and that the acceptability threshold for androstenone, in the absence of skatole, is in the range of 2–3 μg/g liquid fat.

Selectively enhanced cellular signaling by Gi proteins in essential hypertension. G alpha i2, G alpha i3, G beta 1, and G beta 2 are not mutated.

Recent studies have shown an enhanced signaling capacity of receptors coupled to pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G proteins) in immortalized B lymphoblasts from patients with essential hypertension. In the present study, we analyzed (1) whether such alterations would also be expressed in nontransformed cells of these individuals and (2) whether other G protein-mediated signaling pathways were also altered. Therefore, we established primary cultures of skin fibroblasts from previously characterized normotensive and hypertensive individuals (NT and HT cells, respectively). [Ca2+]i rises induced by lyso-phosphatidic acid (LPA), thrombin, and sphingosine-1-phosphate as well as the formation of inositol 1,4,5-trisphosphate and [3H]thymidine incorporation evoked by LPA were PTX sensitive and enhanced twofold in HT fibroblasts. In contrast, cellular responses induced by bradykinin, endothelin-1, and angiotensin II (all PTX insensitive) were similar in NT and HT cells. Formation of cAMP induced by stimulation of Gs with isoproterenol was identical in NT and HT cells. Western blot analysis yielded no evidence for an overexpression of G alpha i2, G alpha i3, G beta 2, and G beta 4. Furthermore, sequencing of cDNAs encoding for the ubiquitously expressed PTX-sensitive G protein subunits G alpha i2, G alpha i3, G beta 1, and G beta 2 from NT and HT cell lines yielded no evidence for mutations in these genes. Although the molecular mechanisms remain to be defined, these data support the concept of a selective enhancement of signal transduction via PTX-sensitive G proteins in essential hypertension.

Different Kinds of Acetylcholine Release From The Motor Nerve

Publisher Summary Studies of transmitter release at the neuromuscular junction have revealed the presence of several distinct types of acetylcholine (ACh) secretion. This chapter describes these processes and discusses the underlying release mechanisms and the possible physiological significance of the various kinds of transmitter action. Transmitter release from the motor nerve may be divided into those involving intermittent, quantal, or nonquantal release of ACh as well as those characterized by a continuous leakage of ACh. Intermittent secretion of ACh involves either a Ca 2+ –sensitive(I) or a Ca 2+ – insensitive (II) type of transmitter release process. The former characterizes phasic, nerve impulse evoked or spontaneous quantal ACh release and the latter the spontaneous intermittent, nonquantal secretion of ACh giving rise postsynaptically to so-called giant and slow-rising miniature end-plate potentials. Molecular leakage of ACh is a continuous process originating not only from the presynaptic nerve (III) but also from the postsynaptic muscle cell.

Genetic heterogeneity of histamine H2-receptors in the mouse vas deferens.

The ability of histamine to inhibit the overall contractile ('twitch') response of the isolated vas deferens of the mouse to electrical field stimulation (64 V pulse, 1 ms pulse width, frequency 0.2 Hz) was studied in nine inbred mouse strains. The strains were also characterized in terms of the potency of the histamine H2-receptor antagonist cimetidine in its inhibition of histamine-mediated effects. An apparently bimodal inter-strain variation (8-10 fold) in both characteristics was encountered, with three strains (SWR, A2G and C57BL/10ScSn) relatively sensitive (S) to both agonist and antagonist actions, and six (C3H, A, C57/BL6, DBA/2, Balb/C and 129/Sv) relatively insensitive (IS). These strain differences were independent of extracellular calcium concentration in the range 1.25-5 mM, and also independent of the frequency of tissue stimulation over the range 0.2-6.4 Hz. Representative S (SWR and A2G) and IS (DBA/2 and C3H) mouse vasa were also characterized in terms of their sensitivity to the agonist actions of dimaprit and the antagonist actions of tiotidine. In the S strain tissues, dimaprit produced 50% inhibition of the twitch response at 4.6-1.8 microM (mean +/- s.d.) and was able to elicit complete inhibition of the twitch response at concentrations greater than 100 microM, whereas 48.7 +/- 11.9 microM dimaprit was required to produce 50% inhibition of the twitch response in tissues from IS mice. In addition, the agonist actions of dimaprit were incomplete in the latter tissues, the drug eliciting no more than 75% inhibition of the twitch response at concentrations in the range 300-1000 microM. Tiotidine produced competitive antagonism of the actions of both histamine and dimaprit, the strain differences being of the same magnitude as those observed for cimetidine. 4 Mating of a representative S (SWR) and IS (129/Sv) strain produced F, mice with intermediate histamine and cimetidine sensitivities relative to the parental strains. A backcross of male F1 to female IS mice produced progeny displaying a range of histamine and cimetidine sensitivities representative of those seen in tissues from F1 and IS parental animals, however, the data were not bimodal. Thus, the backcross data provided no evidence to support single gene inheritance of histamine sensitivity and might suggest that more than one gene is responsible for these differences between S and IS mice.

The Poetry of Geoffrey Hill

The word 'formal' in criticism often associates with ideas concerning metrical iambic, strict stanzaic form and rhyme, and the containment by these devices of whatever the poet has to say. It may be used approvingly, or, since the current has recently run more the other way, as a means of implying that a poet using these forms has little to say, and that his sensibility and imagination are insensi tive, that the courage a poet needs in order to articulate what ought essentially to be his way of exploring life is absent. As corollary to this, it is implied that only what is new in structure can sensitively and honestly engage this, since, it is argued, we are in the midst of such changes that only those forms originated by the poet in co-operation with his constantly changing environment can adequately express the new (as well as the past and hidden) in the tormenting life so many are forced to live.

Insulin Allergy A Report of Eight Cases with Generalized Symptoms

The problem of insulin allergy has been discussed by Tuft (1), Allen and Scherer (2), Herzstein and Pollack (3), McDaniel (4), and among others and most recently by Harten and Walser (5) and by Yasuna (6). Definition. The terms insulin sensitivity and hypersensitivity have been used frequently as synonyms for allergy, but they also have been applied to describe the rapid and excessive hypoglycemic response to insulin in contradistinction to insulin resistance or insensitivity. In this sense, sensitivity differs from allergy completely, not only in symptomatology but also in its mechanism. It may occur with or without allergic symptoms. An attempt should be made, therefore, to differentiate these two conditions in their terminology. In this paper we propose to use the term ‘allergic’ as referring to symptoms which are due to the antigenic property of insulin as a protein substance (7) and to speak of sensitivity and insensitiv ity as referring to the varying degrees of body response to the specific me tabo...