Transforming growth factor-α attenuates hepatic fibrosis: possible involvement of matrix metalloproteinase-1.

Background: The effect of transforming growth factor (TGF)-α on fibrosis varies between cell types and the role of TGF-α in hepatic fibrosis has not been fully elucidated.

Methods: We examined the effect of TGF-α on hepatic fibrosis using TGF-α-expressing transgenic mice fed a methionine- and choline-deficient (MCD) diet and human hepatic stellate cells (HSCs) line LX-2, rat and human primary HSCs.

Results: Although the expression levels of the tissue inhibitor of metalloproteinases-1 and α1(I) collagen mRNA were unchanged, feeding the TGF-α transgenic mice the MCD diet resulted in greater expression of the murine functional analogue of matrix metalloproteinase-1 (MMP-1), MMP-13 mRNA and protein and attenuated hepatic fibrosis compared with wild-type mice.

Specific interactions between lactose repressor protein and DNA affected by ligand binding: ab initio molecular orbital calculations.

Transcription mechanisms of gene information from DNA to mRNA are essentially controlled by regulatory proteins such as a lactose repressor (LacR) protein and ligand molecules. Biochemical experiments elucidated that a ligand binding to LacR drastically changes the mechanism controlled by LacR, although the effect of ligand binding has not been clarified at atomic and electronic levels. We here investigated the effect of ligand binding on the specific interactions between LacR and operator DNA by the molecular simulations combined with classical molecular mechanics and ab initio fragment molecular orbital methods.

A subtraction mechanism of temporal coding in cerebellar cortex.

The temporally specific learning displayed by the cerebellum facilitates mechanistic analysis of neural timing and temporal coding. We report evidence for a subtraction-like mechanism of temporal coding in cerebellar cortex in which activity in a subset of granule cells specifically codes the interval between the offset of two mossy fiber inputs. In a large-scale cerebellar simulation, cessation of one of two ongoing mossy fiber inputs produces a robust temporal code in the population of granule cells.

The effects of the SLCO2B1 c.1457C > T polymorphism and apple juice on the pharmacokinetics of fexofenadine and midazolam in humans.

Objective: The objective was to determine the effects of the SLCO2B1 c.1457C> T polymorphism and apple juice on the pharmacokinetics of fexofenadine and midazolam in humans.

Methods: Individuals were divided based on the genotype of SLCO2B1 c.

Reduction of Peritendinous adhesions by hydrogel containing biocompatible phospholipid polymer MPC for tendon repair.

Background: Peritendinous adhesions are serious complications after surgical repair of tendons. As an anti-adhesion material, we focused on 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, our original biocompatible polymer, and prepared an aqueous solution of MPC-containing polymer called poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-vinylphenylboronic acid) (PMBV), which can be formed into hydrogel properties by mixture with another aqueous polymer, poly(vinyl alcohol) (PVA). The objective of the present study was to examine the possible application of the MPC hydrogel for the reduction of peritendinous adhesions.

HA-33 facilitates transport of the serotype D botulinum toxin across a rat intestinal epithelial cell monolayer.

A large size botulinum toxin complex (L-TC) is composed of a single neurotoxin (BoNT), a single nontoxic nonhaemagglutinin (NTNHA) and a haemagglutinin (HA) complex. The HA complex is comprised of three HA-70 molecules and three arm structures of HA-33/HA-17 that consist of two HA-33 and a single HA-17. In addition to the mature L-TC, smaller TCs are present in cultures: M-TC (BoNT/NTNHA), M-TC/HA-70 and immature L-TCs with fewer HA-33/HA-17 arms than mature L-TC.

SOX9 controls epithelial branching by activating RET effector genes during kidney development.

Congenital abnormalities of the kidney and urinary tract are some of the most common defects detected in the unborn child. Kidney growth is controlled by the GDNF/RET signalling pathway, but the molecular events required for the activation of RET downstream targets are still poorly understood. Here we show that SOX9, a gene involved in campomelic dysplasia (CD) in humans, together with its close homologue SOX8, plays an essential role in RET signalling.

Formyl peptide receptor 1 and 2 dual agonist inhibits human neutrophil chemotaxis by the induction of chemoattractant receptor cross-desensitization.

Formyl peptide receptor 1 (FPR1) and FPR2/ALX are known to control neutrophil chemotaxis in response to various ligands. In this study, we investigated the inhibitory mechanism of compound 43 (Cpd43), an FPR1 and FPR2/ALX dual agonist, on human neutrophil chemotaxis. Precedent stimulation of human peripheral blood neutrophils with Cpd43 rendered the cells unresponsive in calcium mobilization induced by interleukin-8, C5a, or leukotriene B₄.

A decrementing form of plasticity apparent in cerebellar learning.

Long-term synaptic plasticity is believed to underlie the capacity for learning and memory. In the cerebellum, for example, long-term plasticity contributes to eyelid conditioning and to learning in eye movement systems. We report evidence for a decrementing form of cerebellar plasticity as revealed by the behavioral properties of eyelid conditioning in the rabbit.

BMP signaling is necessary for patterning the sensory and nonsensory regions of the developing mammalian cochlea.

The mammalian inner ear detects sound with the organ of Corti, an intricately patterned region of the cochlea in which one row of inner hair cells and three rows of outer hair cells are surrounded by specialized supporting cells. The organ of Corti derives from a prosensory domain that runs the length of the cochlear duct and is bounded by two nonsensory domains, Kölliker's organ on the neural side and the outer sulcus on the abneural side. Although much progress has been made in identifying the signals regulating organ of Corti induction and differentiation, less is known about the mechanisms that establish sensory and nonsensory territories in the cochlear duct.

Inhibition of neutrophil migration in mice by mouse formyl peptide receptors 1 and 2 dual agonist: indication of cross-desensitization in vivo.

It has been reported that the stimulation of neutrophils with N-formyl-Met-Leu-Phe (fMLF), an agonist for formyl peptide receptor (Fpr) 1, renders cells unresponsive to other chemoattractants in vitro. This is known as cross-desensitization, but its functional relevance in neutrophil migration in vivo has not been investigated. Here, we show that precedent stimulation of mouse neutrophils with compound 43, a non-peptidyl agonist for mouse Fpr1 and Fpr2, rendered the cells unresponsive to a second stimulation with C5a, leukotriene B₄, or keratinocyte-derived cytokine (KC) in calcium mobilization and chemotaxis assays in vitro.

Misdiagnosis of two cases of primary aldosteronism owing to failure of computed tomography to detect adrenal microadenoma.

Recent studies have suggested that primary aldosteronism (PA) is a common form of hypertension. However, some cases of PA are overlooked because microadenoma is difficult to detect by imaging. The author report 2 cases in which aldosterone-producing microadenoma was diagnosed by selective adrenal venous sampling (AVS) and furosemide plus upright test.

Positron emission tomography with 18F-fluorodeoxyglucose is a useful tool for the diagnosis of pheochromocytomas without distant metastasis, where malignancy is suspected on the basis of histopathologic analysis.

A 69-year-old woman, who had been undergoing treatment for hypertension, was admitted to the hospital for the evaluation of a tumor in the right adrenal gland and of episodic hypertension. She was diagnosed with pheochromocytoma on the basis of elevated urine catecholamine and metabolite concentrations and positron emission tomography (PET) results; however, the results of I-metaiodobenzylguanidine (I-MIBG) scintigraphy were negative. The patient underwent laparoscopic right adrenalectomy.

Enhancement of the nitrogen fixation efficiency of genetically-engineered Rhizobium with high catalase activity.

The vktA catalase gene, which had been cloned from Vibrio rumoiensis S-1T having extraordinarily high catalase activity, was introduced into the root nodule bacterium, Rhizobium leguminosarum bv. phaseoli USDA 2676. The catalase activity of the vktA-transformed R.

Assimilation and translocation of nitrogen and carbon in Curcuma alismatifolia Gagnep.

Curcuma or Siam tulip (Curcuma alismatifolia Gagnep.) is an ornamental flowering plant with two underground storage organs, rhizomes and storage roots. Characteristics of N and C assimilation and transport in curcuma were investigated.

Temporal patterns of inputs to cerebellum necessary and sufficient for trace eyelid conditioning.

Trace eyelid conditioning is a form of associative learning that requires several forebrain structures and cerebellum. Previous work suggests that at least two conditioned stimulus (CS)-driven signals are available to the cerebellum via mossy fiber inputs during trace conditioning: one driven by and terminating with the tone and a second driven by medial prefrontal cortex (mPFC) that persists through the stimulus-free trace interval to overlap in time with the unconditioned stimulus (US). We used electric stimulation of mossy fibers to determine whether this pattern of dual inputs is necessary and sufficient for cerebellar learning to express normal trace eyelid responses.

Involvement of sialic acid in transport of serotype C1 botulinum toxins through rat intestinal epithelial cells.

Clostridium botulinum produces a large toxin complex (L-TC) composed of neurotoxin (BoNT) and non-toxic proteins. In animal botulism, BoNT or L-TC is absorbed via the intestinal epithelium. To establish the cellular mechanisms of botulinum toxin absorption, we used cultured rat intestinal epithelial cells to test the binding and transport of serotype C1 BoNT and L-TC through the cell layers.

Competence of an artificial bent DNA as a transcriptional activator in mouse ES cells.

Curved DNA structures with a left-handed superhelical conformation can activate eukaryotic transcription. However, their potency in transgene activation in embryonic stem (ES) cells has not been examined. T20 is an artificial curved DNA of 180 bp that serves as a transcriptional activator.

Highly efficient chromatin transcription induced by superhelically curved DNA segments: the underlying mechanism revealed by a yeast system.

Superhelically curved DNA structures can strongly activate transcription in mammalian cells. However, the mechanism underlying the activation has not been clarified. We investigated this mechanism in yeast cells, using 108, 180, and 252 bp synthetic curved DNA segments.

The prevention of peritendinous adhesions by a phospholipid polymer hydrogel formed in situ by spontaneous intermolecular interactions.

Preventing peritendinous adhesions after surgical repair of tendon is difficult. In order to establish an ideal anti-adhesion material, we prepared a spontaneously forming hydrogel by mixing the aqueous solutions of two polymers, poly(MPC-co-methacrylic acid) (PMA) and amphiphilic poly(MPC-co-n-butyl methacrylate) (PMB), in the presence of Fe(3+). This PMA/PMB/Fe(3+) hydrogel (MPC polymer hydrogel) had a honeycomb microstructure with nanometer-scale pores, which resist cell invasion but allow the passage of cytokines and growth factors for tendon healing.

Cerebellar cortex contributions to the expression and timing of conditioned eyelid responses.

We used micro-infusions during eyelid conditioning in rabbits to investigate the relative contributions of cerebellar cortex and the underlying deep nuclei (DCN) to the expression of cerebellar learning. These tests were conducted using two forms of cerebellum-dependent eyelid conditioning for which the relative roles of cerebellar cortex and DCN are controversial: delay conditioning, which is largely unaffected by forebrain lesions, and trace conditioning, which involves interactions between forebrain and cerebellum. For rabbits trained with delay conditioning, silencing cerebellar cortex by micro-infusions of the local anesthetic lidocaine unmasked stereotyped short-latency responses.

Solitary fibrous tumor of the abdominal wall.

Solitary fibrous tumors (SFTs) are uncommon neoplasms of mesenchymal origin that usually arise from the pleura. SFTs of the abdominal wall are extremely rare, and only 12 cases have been reported in the English language literature. This report presents a new case of SFT of the abdominal wall in a 74-year-old female.

The pyrazolone originally reported to be a formyl peptide receptor (FPR) 2/ALX-selective agonist is instead an FPR1 and FPR2/ALX dual agonist.

A pyrazolone compound acting as a formyl peptide receptor (FPR) 2/ALX-selective agonist has been reported, but its pharmacological activities on human FPRs (hFPRs) and mouse FPRs (mFprs) have not been well demonstrated. In this study, we found that this compound, designated as compound A, induced concentration-dependent calcium flux not only in Chinese hamster ovary (CHO) cells expressing hFPR2/ALX but also in cells expressing hFPR1, mFpr1, or mFpr2. It also induced the receptor internalization of hFPR1 and hFPR2/ALX and, accordingly, induced calcium influx and chemotactic responses in both human and mouse neutrophils.

Sialic acid-dependent binding and transcytosis of serotype D botulinum neurotoxin and toxin complex in rat intestinal epithelial cells.

A large toxin complex (L-TC) produced by Clostridium botulinum is composed of neurotoxin (BoNT), non-toxic non-hemagglutinin (NTNHA) and hemagglutinin subcomponents (HA-70, -33 and -17). In animal botulism, BoNT or L-TC is internalized by intestinal epithelial cells. Previous studies showed that L-TC binds to intestinal cells via sugar chains on the cell surface, but the role of toxin binding to sugar chains in the toxin absorption from intestine is unclear.

A synaptic vesicle-associated Ca2+ channel promotes endocytosis and couples exocytosis to endocytosis.

Synaptic vesicle (SV) exo- and endocytosis are tightly coupled to sustain neurotransmission in presynaptic terminals, and both are regulated by Ca(2+). Ca(2+) influx triggered by voltage-gated Ca(2+) channels is necessary for SV fusion. However, extracellular Ca(2+) has also been shown to be required for endocytosis.