Mutations in fibroblast growth factor receptor 2 gene and craniosynostotic syndromes in Japanese children.

We examined the gene mutations of fibroblast growth factor receptor 2 (FGFR2) in Japanese syndromic craniosynostotic patients. Subjects included 1 patient with Apert's syndrome, 1 patient with Crouzon's syndrome, and 3 patients with Pfeiffer's syndrome, as well as two control patients. The genomic deoxyribonucleic acid of each patient was extracted, and the mutation sites of the FGFR2 gene were amplified and sequenced.

Airway and lung tissue behaviour during endothelin-1 induced constriction in rats: effects of receptor antagonists.

Endothelin (ET) 1, a 21 amino acid constrictor peptide, is one of the most potent agonists of airway smooth muscle and acts on two different receptors, i.e., ETA and ETB receptors.

[The effects of pulmonary rehabilitation combined with inspiratory muscle training on pulmonary function and inspiratory muscle strength in elderly patients with chronic obstructive pulmonary disease].

It has been suggested that pulmonary rehabilitation compined with inspiratory muscle training (IMT) might improve pulmonary function and respiratory muscle strength in elderly patients with chronic obstructive pulmonary disease (COPD). To test this hypothesis, inspiratory muscle strength (PImax), expiratory muscle strength (PEmax) and resting pulmonary function were measured in 13 elderly patients with COPD (aged 70.3 +/- 2.

Characterization of a human homolog (BACH1) of the mouse Bach1 gene encoding a BTB-basic leucine zipper transcription factor and its mapping to chromosome 21q22.1.

Clinical interest in the genes on human chromosome 21, especially with respect to Down syndrome (DS), has provided a strong impetus for the creation of a transcript map of this chromosome. In an effort to identify new human genes on the basis of cDNA analysis, we found several cDNA clones that corresponded to chromosome 21-specific transcripts. One of these, ha2303, showed strong similarity to the murine transcription factor Bach1.

Airway hyperresponsiveness to methacholine in mutant mice deficient in endothelin-1.

Endothelin-1 (ET-1) has recently been reported to have a potential pathophysiologic role in bronchial asthma. In the current study, we hypothesized whether ET-1 and a gene encoding ET-1 might be involved in airway hyperresponsiveness (AHR), which is a major feature of bronchial asthma. To test this hypothesis, we investigated airway responsiveness in ET-1(+/-) heterozygous knockout mice, which genetically produce lower levels of ET-1, and in ET-1(+/+) wild-type mice.

[Duration of effect of pulmonary rehabilitation in elderly patients with chronic obstructive pulmonary disease].

Pulmonary rehabilitation has been reported to be effective in patients with chronic obstructive pulmonary disease (COPD). To investigate the effect of a moderate period of pulmonary rehabilitation combined with inspiratory muscle training (IMT) in elderly patients with COPD, we instituted pulmonary rehabilitation for 60 weeks in five elderly patients (age: 65.4 +/- 3.

Characterization of cDNA clones in size-fractionated cDNA libraries from human brain.

To evaluate the size-fractionated cDNA libraries of human brain previously constructed (O. O'hara et al. DNA Research, 4, 53-59, 1997), the occurrence of chimeric clones and the content of clones with coding potentiality were analyzed using the randomly sampled clones with insert sizes of 5 to 7 kb.

Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro.

As a part of our project for accumulating sequence information of the coding regions of unidentified human genes, we herein report the sequence features of 78 new cDNA clones isolated from human brain cDNA libraries as those which may code for large proteins. The sequence data showed that the average size of the cDNA inserts and their open reading frames was 6.0 kb and 2.

p140Sra-1 (specifically Rac1-associated protein) is a novel specific target for Rac1 small GTPase.

Rac1 small GTPase plays pivotal roles in various cell functions such as cell morphology, cell polarity, and cell proliferation. We have previously identified IQGAP1 from bovine brain cytosol as a target for Rac1 by an affinity purification method. By using the same method, we purified a specifically Rac1-associated protein with a molecular mass of about 140 kDa (p140) from bovine brain cytosol.

Trans-regulation of myogenin promoter/enhancer activity by c-ski during skeletal-muscle differentiation: the C-terminus of the c-Ski protein is essential for transcriptional regulatory activity in myotubes.

c-ski gene product is a nuclear protein with myogenesis-promoting and transforming activities. We have analysed the effects of c-ski transfection on the promoter/enhancer activity of the upstream region of the myogenin gene during in vitro myogenesis using CAT reporter assay. When co-transfected with c-ski into myogenic C2C12 cells, promoter/enhancer activity was efficiently suppressed in proliferating cells, but the myogenesis-induced increase in activity was potentiated approximately ten times more (150-fold in the ski-transfected cells) than the ordinary increase (12-fold in the mock) 48 h after induction of differentiation.

Multiple endocrine neoplasia type 1 presented with manic-depressive disorder: a case report with an identified MEN1 gene mutation.

We report a case of multiple endocrine neoplasia type 1 who had repeated hypoglycemic episodes and had previously been diagnosed with bipolar manic-depressive disorder. The patient had a positive family history of multiple endocrine neoplasia type 1 and had multiple pancreatic endocrine tumors, hyperparathyroidism and possibly a pituitary tumor. The pancreatic tumors were resected by subtotal pancreatectomy and examined by histochemical staining and gene analysis.

Airway responsiveness in transgenic mice overexpressing platelet-activating factor receptor. Roles of thromboxanes and leukotrienes.

Platelet-activating factor (PAF) is a potent proinflammatory compound potentially involved in the pathogenesis of inflammatory disorders, including bronchial asthma. To elucidate the pathophysiologic roles of PAF in bronchial asthma, we studied airway responsiveness in transgenic mice overexpressing PAF receptor. In the transgenic mice, PAF-induced airway smooth muscle contraction was demonstrated by physiologic and morphometric analyses, whereas there was no significant response in the littermate control group.

Incorporation of an artificial receptor into a native protein: new strategy for the design of semisynthetic enzymes with allosteric properties.

The sugar-facilitated structure and enzymatic activity change of engineered myoglobins bearing a phenylboronic acid moiety, which were semisynthesized by a cofactor reconstitution method, were studied by the denaturation experiment, spectrophotometric titration of the pKa shift of the axial H2O, circular dichloism (CD), and the kinetics of the myoglobin-catalyzed-aniline hydroxylation reaction. Both boronophenylalanine-appended myoglobin [Mb(m-Bphe)2] and phenylboronic acid-appended myoglobin [Mb(PhBOH)2] were stabilized by approximately 2 kcal/mol upon complexation with D-fructose. CD spectral changes and the sugar-induced pKa shift suggested that the microenvironment of the active site of these myoglobins was re-formed from a partially disturbed state to that comparable to the native state upon D-fructose binding.

Role of cytosolic phospholipase A2 in allergic response and parturition.

Phospholipase A2 (PLA2) comprises a superfamily of enzymes that hydrolyse the ester bond of phospholipids at the sn-2 position. Among the members of this superfamily, cytosolic PLA2 has attracted attention because it preferentially hydrolyses arachidonoyl phospholipids and is activated by submicromolar concentrations of Ca2+ ions and by phosphorylation by mitogen-activated protein kinases (MAP kinases). Here we investigate the function of cytosolic PLA2 in vivo by using homologous recombination to generate mice deficient in this enzyme.

Extensive vesiculobullous eruption following limited ruby laser treatment for incontinentia pigmenti: a case report.

A 3-year-old girl with incontinentia pigmenti was referred for treatment of pigmented whorled macules on the trunk and limbs. Initially ruby laser therapy was only given to the legs. Wound healing was delayed.

[Transfer of genes to human airway epithelial cells in vitro via DNA virus vectors].

Transfer of genes via DNA virus vectors to human airway epithelial cells is not fully understood. We tested the effects of multiplicities of infection (moi) and incubation time on the efficiency of gene transfer by adenovirus vectors and AAV vectors in cultures of human airway epithelial cells. The cells were exposed to Ad-CMV-lacZ or AAV-CMV-LacZ for 1 to 48 hours at different moi from 0.

Tissue and subcellular distributions, and characterization of rat brain protein phosphatase 2A containing a 72-kDa delta/B" subunit.

A 74-kDa delta/B" subunit was isolated by heparin-Sepharose column chromatography from human erythrocyte protein phosphatase 2A (PP2A) consisting of a 34-kDa catalytic subunit (alpha/C) and 63- and 74-kDa regulatory subunits (beta/A and delta/B") in a ratio of 1:1:1. The purified delta/B" was used as an immunogen in mice, to prepare specific antisera against delta/B". Immunoblot analyses with the antisera detected an immunoreactive 72-kDa protein in the cytosol from various rat tissues including erythrocytes, brain, lung, testis, adrenal gland, heart, spleen, kidney, and liver.

Anatomic evaluation of the facial artery and vein using color Doppler ultrasonography.

Despite the importance of preoperative evaluation of small vessels in flap elevation, the conventional methods such as palpation or Doppler probes are technically insufficient. These two methods do not detect varying venous patterns that would be identified during the operation in a "trial-and-error" manner. In order to overcome this problem in the facial vessels, an anatomic study was done using color Doppler ultrasonography in 12 adults.

ET-1-induced bronchoconstriction is mediated via ETB receptor in mice.

Endothelin (ET)-1 is one of the most potent agonists of airway smooth muscle and can act via two different ET receptor subtypes, i.e., ETA and ETB.

Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.

In this series of projects of sequencing human cDNA clones which correspond to relatively long transcripts, we newly determined the entire sequences of 100 cDNA clones which were screened on the basis of the potentiality of coding for large proteins in vitro. The cDNA libraries used were the fractions with average insert sizes from 5.3 to 7.

Colour Doppler flow imaging of postauricular arteries and veins.

The posterior auricular vessels of both ears in 15 normal human adults were examined using a colour Doppler flow imager to investigate whether the imager might be helpful in preoperative assessment of the blood supply of the retroauricular skin. Thirty posterior auricular arteries and 23 posterior auricular veins were identified. A reversed arterial flow was observed in 15 out of 30 ears and a reversed venous flow was observed in 4 out of 30 ears after the blood flow of the vessel was stopped by applying pressure manually at the level of the mastoid process.

Lack of association between the Trp64 Arg mutation in the beta 3-adrenergic receptor gene and obesity in Japanese men: a longitudinal analysis.

The beta 3-adrenergic receptor (beta 3AR) is implicated in the regulation of thermogenesis and lipolysis, and it is suggested that the Trp64 Arg mutation in this receptor may contribute to the development of obesity. To examine whether the Trp64 Arg mutation had any effect on body weight during adult life, the beta 3AR genotype was determined in 186 unselected Japanese men, most of whom had records of body weight measured yearly from 25-53 yr of age. Of them, 26 subjects were diagnosed as having noninsulin-dependent diabetes mellitus (NIDDM) and 41 as having impaired glucose tolerance.

Construction and characterization of human brain cDNA libraries suitable for analysis of cDNA clones encoding relatively large proteins.

Analysis of proteins registered in the PIR protein database implied that most of relatively large proteins are related to important functions in higher multicellular organisms, but not many large proteins have been registered to date. To establish a protocol for efficient analysis of cDNA clones coding for large proteins, we constructed a series of strictly size-fractionated cDNA libraries of human brain, where the average insert sizes of cDNA clones ranged from 3.3 kb to 10 kb.