The leukotriene E4 puzzle: finding the missing pieces and revealing the pathobiologic implications.

The intracellular parent of the cysteinyl leukotrienes (cysLTs), leukotriene (LT) C(4), is formed by conjugation of LTA(4) and reduced glutathione by LTC(4) synthase in mast cells, eosinophils, basophils, and macrophages. After extracellular export, LTC(4) is converted to LTD(4) and LTE(4) through sequential enzymatic removal of glutamic acid and then glycine. Only LTE(4) is sufficiently stable to be prominent in biologic fluids, such as urine or bronchoalveolar lavage fluid, of asthmatic individuals and at sites of inflammation in animal models.

GPR17 is a negative regulator of the cysteinyl leukotriene 1 receptor response to leukotriene D4.

The cysteinyl leukotrienes (cys-LTs) are proinflammatory lipid mediators acting on the type 1 cys-LT receptor (CysLT(1)R) to mediate smooth muscle constriction and vascular permeability. GPR17, a G protein-coupled orphan receptor with homology to the P2Y and cys-LT receptors, failed to mediate calcium flux in response to leukotriene (LT) D(4) with stable transfectants. However, in stable cotransfections of 6xHis-tagged GPR17 with Myc-tagged CysLT(1)R, the robust CysLT(1)R-mediated calcium response to LTD(4) was abolished.

Aberrant ENaC activation in Dahl salt-sensitive rats.

Background: The epithelial sodium channel (ENaC) plays an important role in the regulation of blood pressure by modulating Na reabsorption in the kidney. Dahl salt-sensitive rats on high-salt diet develop severe hypertension, and high-salt diet has been reported to stimulate ENaC mRNA expression in the kidney abnormally in Dahl salt-sensitive rats despite a suppressed plasma aldosterone concentration (PAC).

Methods: We investigated the effect of high-salt diet on ENaC protein expression in Dahl salt-resistant and Dahl salt-sensitive rats, and examined the effect of amiloride (5 mg/kg per day) and eplerenone (0.

[Physical and mental health characteristics of female caregivers].

Objective: In Japan, research into physical conditions or illnesses of female caregivers focusing on biological markers in biological materials such as blood and urine has been limited. Therefore, the present study was conducted to clarify the physical and mental characteristics of female caregivers in comparison with the general population, using biological markers and self-answered questionnaires.

Methods: The subjects were 161 female in-home primary caregivers for persons requiring care at level 3 or more or less than 3 if suffering from dementia (caregiver group).

Group V secretory phospholipase A2 modulates phagosome maturation and regulates the innate immune response against Candida albicans.

Phospholipase A(2) (PLA(2)) hydrolyzes the sn-2 position of cell membrane phospholipids to release fatty acids and lysophospholipids. We have previously reported that group V secretory PLA(2) (sPLA(2)) translocates from the Golgi and recycling endosomes of mouse peritoneal macrophages to newly formed phagosomes and regulates the phagocytosis of zymosan, suggesting a role in innate immunity. Here we report that in macrophages lacking group V sPLA(2), phagosome maturation was reduced 50-60% at early time points while the binding of zymosan was unimpaired.

Induction of mesothelioma by a single intrascrotal administration of multi-wall carbon nanotube in intact male Fischer 344 rats.

The present study assessed a carcinogenic hazard of multi-wall carbon nanotube (MWCNT) in intact (not genetically modified) rodents. MWCNT (1 mg/kg body weight, 7 animals), crocidolite (2 mg/kg body weight, 10 animals) or vehicle (2% carboxymethyl cellulose, 5 animals) was administered to male Fischer 344 rats (12 weeks old) by a single intrascrotal injection. Rats were autopsied immediately after death, when becoming moribund or at the end of the maximal observation period scheduled to be 52 weeks.

Camostat mesilate inhibits prostasin activity and reduces blood pressure and renal injury in salt-sensitive hypertension.

Prostasin, a glycosylphosphatidylinositol-anchored serine protease, regulates epithelial sodium channel (ENaC) activity. Sodium reabsorption through ENaC in distal nephron segments is a rate-limiting step in transepithelial sodium transport. Recently, proteolytic cleavage of ENaC subunits by prostasin has been shown to activate ENaC.

Dectin-2 recognition of house dust mite triggers cysteinyl leukotriene generation by dendritic cells.

House dust mites are a significant source of airborne allergen worldwide, but there is little understanding of how they so potently generate allergic inflammation. We found that extracts from the house dust mites Dermatophagoides farinae (Df) and Dermatophagoides pteronyssinus and from the mold Aspergillus fumigatus stimulated a rapid and robust production of cysteinyl leukotrienes (cys-LTs), proinflammatory lipid mediators, from mouse bone marrow-derived dendritic cells (BMDCs). Con A affinity chromatography of the Df extract revealed that the relevant ligand is a glycan(s), suggesting stimulation via a dendritic cell (DC) lectin receptor.

Long-term treatment with bromocriptine inhibits endometrial adenocarcinoma development in rats.

The effects of long-term blockade of prolactin (PRL) action by bromocriptine (BRC) treatment on uterine carcinogenesis and on related ovarian physiology were investigated using a rat uterine cancer model. Ten-week-old cycling female Donryu rats, a high yield strain for uterine corpus tumors (endometrial adenocarcinomas), were treated with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), as a tumor initiator, and injected with 1 mg/kg body weight BRC subcutaneously 4 times per week until 14.5 months of age to block the proestrus PRL surge.

Development and psychometric evaluation of the Ostomy Adjustment Inventory-23.

Purpose: This article describes the development of the Ostomy Adjustment Inventory-23 (OAI-23), a self-report, multidimensional scale designed to assess psychosocial adjustment in patients with ostomy.

Subjects And Setting: Five hundred seventy persons with a colostomy, ileostomy, or urostomy, who were randomly selected from 3 national databases, provided assessable data.

Results: The results indicate that the OAI-23 is reliable (the Cronbach alpha = .

Category analysis of the substituted anilines studied in a 28-day repeat-dose toxicity test conducted on rats: correlation between toxicity and chemical structure.

In order to establish methods for estimating the repeat-dose toxicity of chemicals on the basis of their chemical structure, an analysis of a category formed for 14 substituted anilines was conducted. This analysis was based on the results of a 28-day repeat-dose toxicity test conducted on rats in which these 14 chemicals were studied. The intensities of the toxicological effects of the 14 substituted anilines on each target organ at specific dosages were described using the values and histopathological findings of the test.

Functional recognition of a distinct receptor preferential for leukotriene E4 in mice lacking the cysteinyl leukotriene 1 and 2 receptors.

The cysteinyl leukotrienes (cys-LTs) are a family of potent lipid mediators of inflammation derived from arachidonic acid. Activation of certain cell types results in the biosynthesis and export of leukotriene (LT) C(4), which then undergoes extracellular metabolism to LTD(4) and LTE(4). LTE(4), the most stable cys-LT, is only a weak agonist for the defined type 1 and type 2 cys-LT receptors (CysLT(1)R and CysLT(2)R, respectively).

Properties, intracellular localization, and stage-specific expression of membrane-bound beta-glucosidase, BglM1, from Physarum polycephalum.

Physarum polycephalum expresses a membrane-bound beta-glucosidase (BglM1) with a molecular mass of 130 kDa. The primary structure of BglM1 consists of a glycosyl hydrolase family 3 domain at an amino-terminal domain and a carboxyl-terminal region without homology to the sequence of known glycosidases. The latter region contains two calx-beta motifs known as Ca(2+)-binding sites; an RGD sequence, which is known to be a cell attachment sequence; and a transmembrane region.

[Surgical repair of traumatic rupture of the discending aorta through 'L'-thoracotomy].

Acute blunt aortic rupture occurs frequently at the aortic isthmus and emergency operation is usually required. A 33-year-old man was suffered with blunt traumatic thoracic aortic injury caused by traffic accident and emergency operation was performed due to hemodynamic instability. The patient was operated through 'L'-thoracotomy (upper part sternotomy and antero-lateral thoracotomy).

High relative biologic effectiveness of carbon ion radiation on induction of rat mammary carcinoma and its lack of H-ras and Tp53 mutations.

Purpose: The high relative biologic effectiveness (RBE) of high-linear energy transfer (LET) heavy-ion radiation has enabled powerful radiotherapy. The potential risk of later onset of secondary cancers, however, has not been adequately studied. We undertook the present study to clarify the RBE of therapeutic carbon ion radiation and molecular changes that occur in the rat mammary cancer model.

Involvement of mutation-based inhibition of beta-catenin phosphorylation at Ser33 in the malignant progression of lung (pre)neoplastic lesions induced by N-nitrosobis(2-hydroxypropyl)amine in male Fischer 344 rats.

In this study we investigated the Ser33 phosphorylation status of beta-catenin protein in relation to genomic mutations in lung (pre)neoplastic lesions induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in male Fischer 344 rats. Six-week-old animals received 2000 ppm of BHP in the drinking water for 8 weeks and were sacrificed 12 weeks thereafter. Histopathologically, 69 of 75 rats demonstrated multiple lung (pre)neoplastic lesions, classified into 27 slight and 33 advanced hyperplasias (preneoplasms) and 61 neoplasms, including adenomas, adenocarcinomas, and adenosquamous carcinomas.

Testicular injury to rats fed on soybean protein-based vitamin B12-deficient diet can be reduced by methionine supplementation.

We have previously reported that rats fed on a vitamin B12 (B12)-deficient diet containing 180 g soybean protein per kg diet showed marked histologic damage in their testes. In this paper, we report the effect of B12-deficiency on B12-dependent methionine synthase in the rats' testes and the effect of methionine supplementation of the diet on testicular damage. Rats were fed the soybean protein-based B12-deficient diet for 120 d.

Hydration process of Na2- in small water clusters: photoelectron spectroscopy and theoretical study of Na2- (H2O)n.

Photoelectron spectroscopy (PES) of Na2- (H2O)n (n < or = 6) was investigated to examine the solvation of sodium aggregates in small water clusters. The PES bands for the transitions from the anion to the neutral ground and first excited states derived from Na2 (1(1)Sigmag+) and Na2 (1(3)Sigmau+) shifted gradually to the blue, and those to the higher-excited states correlated to the 3(2)S + 3(2)P asymptote dropped down rapidly to the red and almost degenerated on the 1(3)Sigmau+-type band at n = 4. Quantum chemical calculations for n up to 3 showed that the spectra can be ascribed to structures where one of the Na atoms is selectively hydrated.

Effect of bread baking on the bioavailability of hydrogen-reduced iron powder added to unenriched refined wheat flour.

Elemental iron powders are widely used to fortify flour and other cereal products. Our objective was to test the hypothesis that baking enhances the bioavailability of elemental iron powders by oxidizing Fe(0) to Fe(2+) or Fe(3+). An in vitro digestion/Caco-2 cell culture model and a piglet model were used to measure bioavailability.

Effect of external static magnetic field on the emittance and total charge of electron beams generated by laser-Wakefield acceleration.

Significant enhancement of emittance and an increase of the total charge of femtosecond electron beams produced by a 12 TW, 40 fs laser pulse, tightly focused in a He gas jet, are observed after applying a static magnetic field, B> or =0.2 T, directed along the axis of laser pulse propagation. The effect appears when plasma produced by a laser prepulse becomes magnetized in the vicinity of the focus point: the electron Larmor frequency exceeds the collisional frequency, while periphery of the plasma remains unmagnetized.

Inhibition of prostasin-induced ENaC activities by PN-1 and regulation of PN-1 expression by TGF-beta1 and aldosterone.

Prostasin has been shown to regulate sodium handling in the kidney. Recently, a serine protease inhibitor, protease nexin-1 (PN-1), was identified as an endogenous inhibitor for prostasin. Therefore, we hypothesized that PN-1 may regulate sodium reabsorption by reducing prostasin activity, and that expression of PN-1 was regulated by transforming growth factor-beta1 (TGF-beta1) or aldosterone, like prostasin.

A cDNA cloned from Physarum polycephalum encodes new type of family 3 beta-glucosidase that is a fusion protein containing a calx-beta motif.

The microplasmodia of Physarum polycephalum express three types of beta-glucosidases: secretory enzyme, a soluble cytoplasmic enzyme and a membrane-bound enzyme. We are interested in the physiological role of three enzymes. We report the sequence of cDNA for membrane beta-glucosidase 1, which consists of 3825 nucleotides that includes an open reading frame encoding 1248 amino acids.

Evidence for a domain-swapped CD4 dimer as the coreceptor for binding to class II MHC.

CD4 is a coreceptor for binding of T cells to APC and the primary receptor for HIV. The disulfide bond in the second extracellular domain (D2) of CD4 is reduced on the cell surface, which leads to formation of disulfide-linked homodimers. A large conformational change must take place in D2 to allow for formation of the disulfide-linked dimer.

Disruption of spermatogenic cell adhesion and male infertility in mice lacking TSLC1/IGSF4, an immunoglobulin superfamily cell adhesion molecule.

TSLC1/IGSF4, an immunoglobulin superfamily molecule, is predominantly expressed in the brain, lungs, and testes and plays important roles in epithelial cell adhesion, cancer invasion, and synapse formation. We generated Tslc1/Igsf4-deficient mice by disrupting exon 1 of the gene and found that Tslc1(-/-) mice were born with the expected Mendelian ratio but that Tslc1(-/-) male mice were infertile. In 11-week-old adult Tslc1(-/-) mice, the weight of a testis was 88% that in Tslc1(+/+) mice, and the number of sperm in the semen was approximately 0.