Pertuzumab and trastuzumab are anti-HER2 humanized monoclonal antibodies with different mechanisms of action. Their combination is expected to suppress intracellular HER2 signaling additively or synergistically. Their combination is widely recommended worldwide and has been established as a standard of care for HER2-positive breast cancer.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
June 2016
The aim of this study was to define the effects of polysulfide on intracellular Ca(2+) concentration ([Ca(2+)]i) and the underlying machinery, especially from the hydrogen sulfide (H2S) and nitric oxide (NO) perspectives, in rat peritoneal mast cells. We found that a polysulfide donor, Na2S4, increased [Ca(2+)]i, which is both extracellular and intracellular Ca(2+) dependent. Intracellular Ca(2+) release induced by Na2S4 was attenuated by the addition of a ryanodine receptor blocker.
View Article and Find Full Text PDFFree Radic Biol Med
January 2016
We aimed to elucidate the interplay among the three well-known gas molecules, nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), and their effects on intracellular Ca(2+) concentration ([Ca(2+)]i) and insulin secretion in rat pancreatic β-cells. Immunofluorescence studies demonstrated the expression of constitutive enzymes that are responsible for the production of NO, CO and H2S. CO and H2S increased NO production as indicated by the increase in diaminofluorescein-2 triazole fluorescence.
View Article and Find Full Text PDFInbreeding avoidance is essential to providing offspring with genetic diversity. Females' mate choice is more crucial than males' for successful reproduction because of the high cost of producing gametes and limited chances to mate. However, the mechanism of female inbreeding avoidance is still unclear.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
October 2015
In addition to nitric oxide (NO), hydrogen sulfide (H2S) is recognized as a crucial gaseous messenger that exerts many biological actions in various tissues. An attempt was made to assess the roles and underlying mechanisms of both gases in isolated rat parotid acinar cells. Ductal cells and some acinar cells were found to express NO and H2S synthases.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
December 2014
Carbon monoxide (CO) is known as an essential gaseous messenger that regulates a wide array of physiological and pathological processes, similar to nitric oxide (NO) and hydrogen sulfide. The aim of the present study was to elucidate the potential role of CO in Ca(2+) homeostasis and to explore the underlying mechanisms in pancreatic acinar cells. The exogenous application of a CO-releasing molecule dose-dependently increased intracellular Ca(2+) concentration ([Ca(2+)]i).
View Article and Find Full Text PDFAim: The present study was designed to explore the effects of hydrogen sulfide (H2S) on Ca(2+) homeostasis in rat pancreatic acini.
Results: Sodium hydrosulfide (NaHS; an H2S donor) induced a biphasic increase in the intracellular Ca(2+) concentration ([Ca(2+)]i) in a dose-dependent manner. The NaHS-induced [Ca(2+)]i elevation persisted with an EC50 of 73.
The rodent preputial gland is one of the major sources of odours and is reported to be involved in several behavioural activities. However, how the preputial gland initiates the olfactory response to manifest the effects is not known. Olfactory receptor neurons (ORNs) present in the olfactory epithelium are involved in the perception of odorant/pheromonal compounds.
View Article and Find Full Text PDFThe c-myc transcriptional suppressor, far-upstream element (FUSE)-binding protein (FBP)-interacting repressor (FIR), is alternatively spliced in colorectal cancer tissue (Matsushita et al., Cancer Res 2006). Recently, the knockdown of SAP155 pre-mRNA-splicing factor, a subunit of SF3b, was reported to disturb FIR pre-mRNA splicing and yield FIRΔexon2, an exon 2-spliced variant of FIR, which lacks c-myc repression activity.
View Article and Find Full Text PDFThe odor preference of female mice for male odor is reported to have cyclical variations in relation to the estrus cycle. Females prefer the odor of genetically dissimilar males to that of genetically similar ones, but the causal relation between this preference and the estrus cycle has scarcely been investigated. The Y-maze test demonstrated that BALB/c females stayed for a longer duration near the urine of C57BL/6 males than that of BALB/c males when they were in metestrus, diestrus and proestrus, but not in estrus.
View Article and Find Full Text PDFSqualene in the rat clitoral gland is reported to be semi-volatile and may serve as a chemo-signal. The objective was to determine squalene concentrations in the clitoral gland throughout the reproductive cycle. Clitoral glands were extracted with dichloromethane; 23 compounds were identified with Gas Chromatography linked Mass Spectrometry (GC-MS).
View Article and Find Full Text PDFIn an attempt to explore the functioning of nitric oxide (NO) in pancreatic exocrine cells, we have recently obtained several lines of circumstantial evidence indicating that one of molecular targets of NO is phospholipase C (PLC), the activation of which leads to an increase in the cytosolic Ca2+ concentration ([Ca2+]i) via inositol 1, 4, 5-trisphosphate, IP3. However, whether IP3 is actually produced by NO has not yet been substantiated. The present study was therefore designed to directly measure the intracellular IP3, concentration ([IP3]i) for better understanding of the underlying mechanisms with the help of pharmacological tools.
View Article and Find Full Text PDFThe aim of the present study was to investigate the possible interaction between intracellular Ca(2+) and nitric oxide (NO) in rat pancreatic acinar cells, especially intracellular signaling events. (1) Nitric oxide donors SNP (0.1-100 μM) and NOR-3 (50-400 μM) induced Ca(2+) oscillations in fluo-4-loaded acini, that appeared to be analogous to what we usually observe in acini stimulated with physiological secretagogues such as CCK-8 and this oscillations were abolished in the presence of carboxy-PTIO.
View Article and Find Full Text PDFPreputial gland is one of the best known and most odour-producing organs in many non-primate mammals. It is generally believed that the development of this gland and functions are regulated by testosterone. To substantiate this point, the present study was aimed to evaluate the testosterone-dependent volatile compounds and proteins in the preputial gland of rat adopting castration and testosterone supplementation.
View Article and Find Full Text PDFWe investigated the blood status of 9 Weddell seal mothers and 9 pups during the breeding season in a field study conducted from November to December 2004 at a breeding colony in Antarctica. The blood glucose and total cholesterol concentrations were higher in the pups than in the mothers. On the other hand, the blood urea nitrogen concentration was lower in the pups than in the mothers.
View Article and Find Full Text PDFProlonged abnormal vomiting causes metabolic alkalosis. Many seabirds are known to feed their chicks by regurgitation. We hypothesized that metabolic alkalosis occurs in seabirds even under natural conditions during the breeding season.
View Article and Find Full Text PDFBackground: Splicing patterns are critical for assessing clinical phenotype of mutations in the dystrophin gene. However, it is still unclear how to predict alternative splicing pathways in such cases of splice-site mutation in the dystrophin gene.
Objective: To identify elements determining alternative splicing pathways in intron +1G-->A mutations of the dystrophin gene.
Secondary alterations in splicing have been reported to produce semi-functional mRNA from several nonsense mutations in the dystrophin gene. Disruptions of exonic splicing enhancers by single nucleotide changes are thought to underlie such alterations. The precise frequencies of such nonsense mutation-dependent splicing alterations, however, remain unknown.
View Article and Find Full Text PDFThe lanceolate sensory endings that form palisades around the hair follicle associate with networks of branched Schwann cells. To define the properties of these glial networks as possible conduits of Ca2+ signals, lanceolate endings isolated from rat vibrissae were observed by confocal microscopy while the signaling was locally activated by mechanical stimulation. Intercellular coupling by gap junctions was also assessed by a technique employing fluorescence recovery after photobleaching (FRAP) and by transmission electron microscopy (TEM).
View Article and Find Full Text PDFBipolar vomeronasal sensory neurons (VSNs) in the vomeronasal organ (VNO) are believed to detect pheromones in most mammals. The vomeronasal sensory epithelium (VSE) is composed of VSNs and supporting cells. There are morphological differences in VNOs between species.
View Article and Find Full Text PDFProper splicing is known to proceed under the control of conserved cis-elements located at exon-intron boundaries. Recently, it was shown that additional elements, such as exonic splicing enhancers (ESEs), are essential for the proper splicing of certain exons, in addition to the splice donor and acceptor site sequences; however, the relationship between these cis-elements is still unclear. In this report, we utilize dystrophin exon 19 to analyse the relationship between the ESE and its upstream acceptor site sequences.
View Article and Find Full Text PDFThe present study was designed to identify the volatile constituents across the oestrous cycle of bovine in order to detect oestrous-specific chemical signal. The bovine saliva was extracted with diethyl ether (1 : 1 ratio, v/v) and analysed by gas chromatography-linked mass spectrometry. Numerous compounds were identified during oestrous cycle of bovine saliva.
View Article and Find Full Text PDFThe dystrophin gene, which is mutated in Duchenne and Becker muscular dystrophy, is characterized by its extremely large introns. Seven cryptic exons from the intronic sequences of the dystrophin gene have been shown to be inserted into the processed mRNA. In this study, we have cloned seven novel cryptic exons embedded in dystrophin introns that were amplified from dystrophin mRNA isolated from lymphocytes.
View Article and Find Full Text PDFIn the Drosophila embryo, Nanos and Pumilio collaborate to repress the translation of hunchback mRNA in the somatic cytoplasm. Both proteins are also required for repression of maternal Cyclin B mRNA in the germline; it has not been clear whether they act directly on Cyclin B mRNA, and if so, whether regulation in the presumptive somatic and germline cytoplasm proceeds by similar or fundamentally different mechanisms. In this report, we show that Pumilio and Nanos bind to an element in the 3' UTR to repress Cyclin B mRNA.
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