We investigated the in vivo effects of recombinant human hepatocyte growth factor (HGF) on epithelial cell proliferation in normal mouse lung and on the repair process that follows bleomycin-induced lung injury. Intratracheal administration of 100 micrograms of rhHGF to C57BL/6 mice led to proliferation of bronchial and alveolar epithelial cells as indicated by an increased number of cells staining for proliferating cell nuclear antigen (PCNA). The effect of HGF on the lung repair process was examined by administration of 100 micrograms of rhHGF on Day 3 and Day 6 after intratracheal injection of bleomycin to mice. We found that HGF significantly attenuated collagen accumulation induced by bleomycin as determined by quantitation of hydroxyproline content and by scoring of the extent of fibrosis. To explore the potential mechanisms involved in the beneficial effects of HGF, we performed in vitro studies with A549 pulmonary epithelial cells and found that HGF enhanced cell surface plasmin generation, expression of u-PA activity, and cell migration. In summary, HGF has potent in vivo and in vitro effects on epithelial cells, which suggests it may have a role in the therapy of pulmonary fibrosis.

These data indicate that Th1 cells predominate in the nonpregnant endometrium, especially during the proliferative phase, while Th2 cells predominate in early pregnancy decidua.

Aspirin-intolerant asthma (AIA) is a subtype of bronchial asthma characterized by development of bronchoconstriction evoked by non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibit the cyclooxygenase pathway, leading to enhancement of the lipoxygenase pathway. We evaluated allelic association of 370 single nucleotide polymorphisms (SNPs) of 63 candidate genes, mostly from the arachidonic acid metabolic cascade, with AIA. After two rounds of screening with 198 AIA patients, multiple SNPs in the prostaglandin E(2) receptor subtype 2 (EP2) gene were associated with AIA (P<0.05). Among the 77 SNPs identified in the EP2 gene, we selected 17 SNPs on the basis of linkage disequilibrium and allelic frequencies (minor allele frequency >0.1) for further association study. SNPs in the promoter region of the EP2 gene, uS5, uS5b, and uS7, were significantly associated with AIA (permutation P=0.039-0.001). Analysis of haplotypes constructed according to the LD pattern showed a significant association with AIA (permutation P=0.001). The most significantly associated SNP, uS5, located in the regulatory region of the EP2 gene, was in a STATs-binding consensus sequence [AIA 31.1% versus control 22.1% (permutation P=0.0016) or versus aspirin-tolerant asthma 22.2% (permutation P=0.0017)]. Although STAT1 binding was not observed in gel mobility shift assay with HeLa nuclear extract, an unidentified protein was specifically bound to the allelic sequence. In in vitro reporter assay in HCT116 cells, the site containing the uS5 allele showed reduced transcription activity. Taken together, these results suggest that uS5 allele serves as a target of a transcription repressor protein. A functional SNP of the EP2 gene associated with risk of AIA should decrease the transcription level, resulting in reduction of the PGE(2) braking mechanism of inflammation and involvement in the molecular mechanism underlying AIA.

BACKGROUND: Chlorella vulgaris is a green microalgae that contains various pigment components of carotenoids and chlorophylls. Supercritical CO 2 is widely used for extraction of pharmaceutical compounds because it is non-oxic and easily separated from extracted material by simply depressurizing. In this work, pharmaceutical compounds from Chlorella vulgaris have been extracted using supercritical CO 2 with or without entrainer at various extraction conditions.

ABSTRACT. Canine necrotizing meningoencephalitis (NME) and granulomatous meningoencephalomyelitis (GME) were compared pathologically. Gross observation exhibited lateral ventricular dilation and discoloration, malacia and/or cavitation of the cerebrum in NME. On the contrary, gross changes were milder in GME, except for occasional visible granulomatous mass formation. Histopathologically, the lesions of NME were distributed predominantly in the cerebral cortex and various degrees of inflammatory and necrotic changes were observed according to clinical stages. Besides, microscopic lesions of GME were mainly distributed in the white matter of the c erebrum, cerebellum and brainstem, which are characterized by perivascular cuffing, multiple granulomas and leptomeningeal infiltrates. Although macrophages and lymphocytes were predominant in the inflammatory lesions of both disorders, macrophages in GME transformed into epithelioid cells and exhibited more massive infiltration. Although lectin RCA-1-reactive cells were numerous in both disorders, lysozyme immunoreactive cells in NME were fewer than that in GME. Parenchymal infiltration of MAC387-positive cells was common in GME and limited in NME. The number of CD3-positive lymphocytes in the GME lesions tended to be greater than in NME, though the difference was not statistically significant. Morphological and immunohistochemical differences of the lesions, in particular, the characteristics of infiltrative macrophages may reflect these different pathogeneses of the two disorders. KEY WORDS: canine, granulomatous meningoencephalomyelitis, macrophage, necrotizing meningoencephalitis.J. Vet. Med. Sci. 65(11): 1233-1239, 2003 Canine necrotizing meningoencephalitis (NME) is a unique inflammatory disorder in small-sized breed dogs, especially in Pug dogs. The disease is histopathologically characterized by inflammatory changes consisting of lymphocytic, plasmacytic and histiocytic infiltrations and apparent parenchymal necrosis located mainly in the cerebral cortex [9,15,23]. The common clinical features are forebrain signs such as partial or generalized seizure, decreased consciousness, abnormal behavior, circling and ataxia [9,23]. The cause of NME is still unknown. However, our previous report showed that a certain autoantibody against a canine brain tissue was detected in the cerebrospinal fluid (CSF) and serum, which may suggest an autoimmune pathology in NME [25].The pathological features of NME are often compared with granulomatous meningoencephalomyelitis (GME) that is another inflammatory disease of unknown cause [5,8,23]. Although there are some differences such as breed predilection, the distribution of lesions and the presence or absence of necrotic foci, GME and NME show similar histological changes, i.e., meningitis and perivascular cuffing composed of mononuclear cells including lymphocytes and monocyte/histiocyte-lineages [5,8,23]. Kipar et al. [14] revealed lesions in GME are predominantly composed of CD3 antigen-positive T lymphocytes and a heterogeneo...

The double helix of DNA is one of the most attractive targets in organic and supramolecular chemistry because of its key biological structures and functions. It is composed of complementary strands derived from the homochiral component (d-sugars) and as a consequence, results in the overall righthanded double-helical structure. The metal-directed doublestranded helicates [1] and hydrogen-bonding-driven assemblies of some aromatic oligoamides [2] are known to form double helices. In contrast with DNA, these double helices lack the complementarity between the two strands and have not yet been used for supramolecular catalysis.[3] However, recent discoveries of DNA-based biocatalysts, DNAzymes, [4] and metal-bound DNA hybrid catalysts [5] for enantioselective reactions imply the potential ability of double helices as a promising chiral framework for enantioselective catalysis. Herein we show that complementary double-helical molecules showing optical activity owing to its helicity can be enantioselectively synthesized and can catalyze an asymmetric reaction in the presence of a metal ion; the double-helix framework with controlled helicity is essential for its high enantioselectivity. This approach suggests the broad potential of double-helix catalysis in asymmetric synthesis, which will provide an important step toward more-effective DNAzymelike supramolecular catalysts with sequential information.The design and synthesis of enantiomeric double helices is based on our recently developed strategy with amidinium carboxylate salt bridges, which assist the intertwining of the two crescent-shaped complementary molecular strands, [6] as illustrated in Scheme 1. The two complementary molecular strands 1 and 2 bear achiral amidine and carboxy groups, respectively, and the m-terphenyl units are linked through Pt II acetylide complexes with chiral (R)-or (S)-2-diphenylphosphino-2'-methoxy-1,1'-binaphthyl (MOP) or achiral triphenylphosphine (PPh 3 ) ligands. Upon complexation, 1 and 2 are intertwined with each other through amidinium carboxylate salt bridges, resulting in the double helix 1·2 on which the bias in the twist sense could be induced and controlled by the chiral phosphine groups (MOP) on the Pt II atoms. The interstrand ligand-exchange reaction on the Pt II atoms by using an achiral diphosphine ligand, such as bis(diphenylphosphino)methane (dppm), leads to the bridged double helix 3, which no longer has any chiral components except for helicity. We anticipated that the bias in the twist sense of 3 would be retained if the bridging diphosphine bind the two complementary molecular strands strongly enough to retard the racemization.To this end, the diamidine strand (R)-1 a was complexed with the achiral dicarboxylic acid strand 2 through the saltbridge formation in CDCl 3 . The duplex formation was confirmed by cold-spray ionization mass spectrometry (CSI-MS) measurements; the CSI-MS spectrum of a 2+ , respectively (see Figure S1 in the Supporting Information).[7] The 31 P NMR spectrum (200 MHz, CDCl 3 ) of (R)-1 ...

nIFNγ-autoAbs were present in most patients with disseminated NTM infection without a diagnosis of clinical immunodeficiency. Diagnosis of disseminated NTM requires a high degree of suspicion and can be improved by measuring serum nIFNγ-autoAb titer. Long-term antibiotic therapy helps prevent recrudescent NTM infection.

Objective and methodsDysferlin encoded by DYSF deficiency leads to two main phenotypes, limb girdle muscular dystrophy (LGMD) 2B and Miyoshi myopathy. To reveal in detail the mutational and clinical features of LGMD2B in Japan, we observed 40 Japanese patients in 36 families with LGMD2B in whom dysferlin mutations were confirmed.Results and conclusionsThree mutations (c.1566C>G, c.2997G>T and c.4497delT) were relatively more prevalent. The c.2997G>T mutation was associated with late onset, proximal dominant forms of dysferlinopathy, a high probability that muscle weakness started in an upper limb and lower serum creatine kinase (CK) levels. The clinical features of LGMD2B are as follows: (1) onset in the late teens or early adulthood, except patients homozygous for the c.2997G>T mutation; (2) lower limb weakness at onset; (3) distal change of lower limbs on muscle CT at an early stage; (4) impairment of lumbar erector spinal muscles on muscle CT at an early stage; (5) predominant involvement of proximal upper limbs; (6) preservation of function of the hands at late stage; (7) preservation of strength in neck muscles at late stage; (8) lack of facial weakness or dysphagia; (9) avoidance of scoliosis; (10) hyper-Ckaemia; (11) preservation of cardiac function; and (12) a tendency for respiratory function to decline with disease duration. It is important that the late onset phenotype is found with prevalent mutations.