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Biomedical subjects

T Niimi

Publications and source records attributed to T Niimi.

At least 19 recordsLinked to original sources
PubMed1999

Serum lysozyme levels and clinical features of sarcoidosis.

Serum lysozyme is used as a marker of sarcoidosis disease activity. In this study we examined the association between lysozyme levels and the clinical features of sarcoidosis and thus the clinical usability of this parameter in a large population. One hundred ten sarcoidosis patients from central Japan were examined for clinical features and serum lysozyme level at the first visit to our hospital and on a regular basis thereafter. The sensitivity of lysozyme for predicting sarcoidosis was 79.1%, whereas that of serum angiotensin-converting enzyme (ACE) was 59.0%. Even in the cases without an elevated serum ACE level, a value of 72.1% was obtained. The serum lysozyme level demonstrated a significant tendency to increase with the number of organs involved (p < 0.01). There were significant differences among the four radiographic stages (p < 0. 05). The maximum serum lysozyme levels of patients without a disappearance of abnormal shadows on chest radiography within 5 years were significantly greater than those of individuals with a disappearance (p < 0.05). A positive correlation between serum lysozyme and serum ACE levels was observed. Because serum lysozyme is much less specific for sarcoidosis than serum ACE, its diagnostic value may be limited. However, the sensitivity was high even when serum ACE levels were within normal limits and correlated well with clinical features in sarcoidosis. Therefore, this parameter seems suitable for disease monitoring in proven cases.

Clinical Enzyme Tests↗
PubMed1999

A Drosophila gene encoding multiple splice variants of Kazal-type serine protease inhibitor-like proteins with potential destinations of mitochondria, cytosol and the secretory pathway.

A Drosophila gene (KAZ1), mapped to cytological position 61A1-2 on chromosome 3, has been cloned and found to encode multiple splice variants of Kazal-type serine protease inhibitor-like proteins. KAZ1 consists of five exons and four alternatively retained introns to produce six transcripts of type AB, C1, C2, C3, D and E. The AB transcript contains two ORFs, of which the upstream one produces a polypeptide alpha, which has a mitochondrial sorting signal. Localization to mitochondria was confirmed by expression in COS1 cells. The downstream ORF is shared partially with type C1, C2, C3, D and E transcripts and produces polypeptides beta, gamma, delta and epsilon when expressed in Drosophila cells. Type C1, C2 and C3 transcripts differ only in the 5'-noncoding sequence and thus all produce type gamma. Polypeptides gamma and epsilon have a signal sequence at their N-termini and are secreted into the medium while beta and delta lack this sequence and remain in the cytoplasm. Isoforms beta and epsilon share a common C-terminal sequence distinct from that shared by polypeptides gamma and delta. The N-terminal sequences of isoforms beta to epsilon contain a PEST region which could induce rapid intracellular degradation of isoforms beta and delta. Sequence analysis of the Kazal-type domain suggests a similar folding pattern as observed for rhodniin and SPARC/BM-40. Northern analysis and in situ hybridization showed that the type C3 transcript is predominant and the expression is highest in midgut at larval stage.

Amino Acid Sequence↗
PubMed1999

Brachyury (T) expression in embryonal carcinoma P19 cells resembles its expression in primitive streak and tail-bud but not that in notochord.

Brachyury (T) is involved in mesoderm induction during early mouse development. T expression in embryonal carcinoma P19 cells, which differentiate into mesoderm derivatives in vitro, was studied. Endogenous T expression in P19 cells was transiently induced when the cells were allowed to form aggregates. This expression was enhanced by dimethyl sulfoxide. In situ hybridization showed that T expressing cells formed clusters on the aggregates. Transfection of plasmids encoding reporter genes under the control of the upstream region of T showed that the sequence up to -351 bp can resemble the differentiation-dependent expression of T in P19 cells. To define the promoter region regulating T expression, transgenic mice carrying LacZ under the control of the upstream region were prepared. The region up to -351 bp is sufficient to direct the expression in the primitive streak and tail-bud. The upstream region up to -2400 bp does not support expression in the notochord. The sequence between -987 and -585 bp enhances expression in the primitive streak and tail-bud. In the tail-bud where new cells for elongation of the anteroposterior axis were continuously supplied, the sequence up to -987 bp drove lacZ expression in gut endoderm and prospective neuroectoderm as well as in mesoderm derivatives.

Animals↗
PubMed1999

Vitamin D receptor gene polymorphism in patients with sarcoidosis.

The active form of vitamin D, 1,25-dihydroxyvitamin D(3), is known to be produced at sites of granulomatous reactions in sarcoidosis. 1, 25-dihydroxyvitamin D(3) has multiple immunomodulatory effects, and acts as a promoter of multinucleated giant cell formation. Polymorphism of the vitamin D receptor (VDR) gene has recently been shown to be related to bone mineral density, and also associated with hyperparathyroidism and risk of prostatic carcinoma. Considering that this might affect sarcoidosis, we investigated polymorphism of the VDR gene in 101 patients with sarcoidosis and 105 healthy control subjects. Their genotypes were determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism. In the patients with sarcoidosis, the BB, Bb, and bb genotypes accounted for 1.0%, 37.6%, and 61.4%, whereas in healthy control subjects the figures were 1.0%, 20.0%, and 79.0%, respectively. The difference in the genotype distribution between healthy control subjects and sarcoidosis patients was significant (p < 0.05) with the frequency of the B allele being elevated (p < 0.05). From the result, we suggest that in VDR gene polymorphism the B allele might be a genetic risk factor for sarcoidosis.

Alleles↗
PubMed1999

Direct regulatory interaction of the eyeless protein with an eye-specific enhancer in the sine oculis gene during eye induction in Drosophila.

The Pax-6 gene encodes a transcription factor with two DNA-binding domains, a paired and a homeodomain, and is expressed during eye morphogenesis and development of the nervous system. Pax-6 homologs have been isolated from a wide variety of organisms ranging from flatworms to humans. Since loss-of-function mutants in insects and mammals lead to an eyeless phenotype and Pax-6 orthologs from distantly related species are capable of inducing ectopic eyes in Drosophila, we have proposed that Pax-6 is a universal master control gene for eye morphogenesis. To determine the extent of evolutionary conservation of the eye morphogenetic pathway, we have begun to identify subordinate target genes of Pax-6. Previously we have shown that expression of two genes, sine oculis (so) and eyes absent (eya), is induced by eyeless (ey), the Pax-6 homolog of Drosophila. Here we present evidence from ectopic expression studies in transgenic flies, from transcription activation studies in yeast, and from gel shift assays in vitro that the EY protein activates transcription of sine oculis by direct interaction with an eye-specific enhancer in the long intron of the so gene.

Animals↗
PubMed1999

[Nontuberculous mycobacterial disease in a general hospital].

Annual incidence of nontuberculous mycobacterial (NTM) disease has been gradually increasing in the last 10 years in Japan. It is likely to encounter this disease not only in hospitals specialized in mycobacterial diseases but also in general hospitals. NTM were isolated from 97 cases between January 1990 and June 1996 at our hospital. Out of them, 41 patients were diagnosed as NTM disease. Mycobacterium avium complex (MAC) was the most frequent pathogens (68.3%) and M. kansasii (22%) was the next. Other pathogens were M. chelonae (4.9%), M. fortuitum (2.4%) and M. szulgai (2.4%). Results obtained in our hospital were very similar to the rates which have been reported previously. Patients with MAC infection showed relatively poor prognosis (eight patients were died out of 28 patients with MAC) in this study compared with the cases reported in previous papers, and this result could be explained by the severity of illness when they were admitted to our hospital, the insufficiency of the initial treatment which should be started with the combined use of three to four antibacterial drugs including clarithromycin, and to a low dosage of clarithromycin compared with conventionally adopted dosage. Unlike tuberculosis, human to human transmission is considered to be negligible in the case of NTM disease, and general hospitals are able to provide medical care to the patients with NTM disease. Rather, if general hospitals which are located in the region near to the patients residence can play more active role in the treatment of NTM disease, it would be more beneficial to patients requiring long-term follow-up observation. Based on the result that similar therapeutic results were obtained for infections with other NTM as reported in previous papers, it is indicated that general hospitals are able to provide medical care to patients with NTM disease if therapeutic regimens recommended by specialist are sufficiently understood and applied.

Female↗
PubMed1998

Structural basis for binding of the plasmid ColIb-P9 antisense Inc RNA to its target RNA with the 5'-rUUGGCG-3' motif in the loop sequence.

The sequence 5'-rUUGGCG-3' is conserved within the loop regions of antisense RNAs or their targets involved in replication of various prokaryotic plasmids. In IncIalpha plasmid ColIb-P9, the partially base paired 21-nucleotide loop of a stem-loop called structure I within RepZ mRNA contains this hexanucleotide sequence, and comprises the target site for the antisense Inc RNA. In this report, we find that the base pairing interaction at the 5'-rGGC-3' sequence in the hexanucleotide motif is important for interaction between Inc RNA and structure I. In addition, the 21-base loop domain of structure I is folded tighter than predicted, with the hexanucleotide sequence at the top. The second U residue in the sequence is favored for Inc RNA binding in a base-specific manner. On the other hand, the upper domain of the Inc RNA stem-loop is loosely structured, and maintaining the loop sequence single-stranded is important for the intermolecular interaction. Based on these results, we propose that a structural feature in the loop I domain, conferred probably by the conserved 5'-rUUGGCG-3' sequence, favors binding to a complementary, single-stranded RNA. This model also explains how the RepZ mRNA pseudoknot, described in the accompanying paper (Asano, K., and Mizobuchi, K. (1998) J. Biol. Chem. 273, 11815-11825) is formed specifically with structure I. A possible conformation adopted by the 5'-rUUGGCG-3' loop sequence is discussed.

Bacterial Proteins↗
PubMed1998

Combined surgery for mitral regurgitation associated with extensive annular calcification and left main coronary artery disease.

Although extensive calcification of the mitral annulus is encountered infrequently, it presents a formidable problem in mitral valve surgery. We describe a case of severely calcified mitral annulus associated with grade IV mitral regurgitation in addition to left main coronary artery disease. The patient was a 66-year-old woman who successfully underwent thorough excision of the calcified bar, annular reconstruction with a autologous pericardial strip, mitral valve replacement with a mechanical prosthesis, and double coronary artery bypass grafting using arterial grafts.

Aged↗
PubMed1998

Genetic polymorphism of the angiotensin-converting enzyme (ACE) in asthmatic patients.

Angiotensin-converting enzyme (ACE) inactivates bradykinin, substance P and neurokinin A, which are believed to play important roles in the pathogenesis of asthma, especially in neurogenic inflammation. It has recently been shown that an insertion (I)/deletion (D) polymorphism in the ACE gene accounts for variation in serum ACE levels. There are thus three genotypes (insertion homozygote, II; deletion homozygote, DD; heterozygotes, DI). The serum ACE level with the DD type is reported to be about double that of the II type and intermediate in the DI case. In the present study, we examined whether asthma is linked with this ACE gene polymorphism. Seventy-one patients with asthma (27 males and 44 females) and 142 sex- and age-matched healthy controls were determined for their genotype by the polymerase chain reaction (PCR) method. Twenty-five asthmatics demonstrated the II type (35.2%), 37 the DI type (52.1%), and nine the DD type (12.7%). There were no significant differences in the distributions of genotypes and serum ACE levels between healthy controls and patients. No significant differences were evident in serum IgE levels, age at onset, proportion of atopic type patients and severity of asthma among the three genotypes. We did not find any association between asthma and the ACE gene polymorphism in this study.

Asthma↗
PubMed1998

A hydrophobic peptide (VAP-peptide) of the silkworm, Bombyx mori: a unique role for adult activity proposed from gene expression and production at the terminal phase of metamorphosis.

A unique hydrophobic peptide (VAP-peptide) isolated from male adult heads of the silkworm, Bombyx mori, has been shown to act as a synergist to the diapause hormone when administered exogenously. Here, we investigated the true role of the endogenous VAP-peptide on differentiation and development of adult organs in the silkworm. By northern blot analyses, the VAP-peptide gene was shown to be exclusively expressed at the terminal phase of adult development in epithelial tissues, especially in the wing and the thoracic integument. In situ hybridization analysis revealed that the gene was highly expressed in the epidermal cells of the wing vein and the thoracic integument. The stage- and tissue-dependent gene expression were clearly correlated to the accumulation profile of VAP-peptide. In the adult thoracic integument, VAP-peptide was predominantly deposited in the cuticle layer. Affinity chromatography indicated the ability of VAP-peptide to bind to chitin. Based on its expression patterns, localization, and chemical properties, VAP-peptide is conceived to be a structural protein that participates in mechanical strengthening of specific cuticle structures, supporting their physical requirements in the adult life of the silkworm.

Animals↗
PubMed1998

p53 mutations in non-small-cell lung cancers occurring in individuals without a past history of active smoking.

Accumulating evidence suggests that the p53 gene is a good target for molecular epidemiological studies. We previously reported an association between the presence of p53 mutations and lifetime cigarette consumption. Although over 675 p53 mutations have been reported in lung cancers in the literature thus far, very little is known about the nature of such changes in lung cancers in the absence of a smoking background. In the present study, we therefore analysed 69 non-small-cell lung cancer specimens from individuals without any history of active smoking and identified p53 mutations in 26% of the cases. Statistical analysis of the present cohort of non-smokers also showed absence of significant relationship between p53 mutations and age, sex, histological type or disease stage. Comparison of mutational spectra between the present results in non-smokers and previously reported mutations in smokers clearly demonstrated G:C to T:A transversions to be significantly less frequent in non-smokers than in smokers (OR 5.35, 95% CI 1.77-16.12). Interestingly, G:C to C:G and G:C to A:T mutations were also observed in tumours of non-smokers at similar frequencies to G:C to T:A mutations, suggesting that these mutations can occur relatively frequently in the absence of active smoking. This study is, to our knowledge, the largest so far analysing a well-defined cohort of non-smokers in a single laboratory.

Adult↗
PubMed1998

The "T-shaped" thoracotomy for pericardiectomy after midline crossed IMA grafting.

In the presence of an internal mammary artery graft crossing the mid-sternal line, a median sternotomy may jeopardize the graft and consequently bring a hemodynamic compromise. We describe a case of successful radical pericardiectomy for postoperative constrictive pericarditis using a "T-shaped" thoracotomy in a 68-year-old male patient who had a right IMA graft to the left anterior descending coronary artery.

Aged↗
PubMed1998

Bronchial responsiveness and angiotensin-converting enzyme gene polymorphism in sarcoidosis patients.

BACKGROUND: Angiotensin-converting enzyme (ACE) inactivates bradykinin and tachykinins, which are potent bronchoconstrictors and mediators of inflammatory reactions. It has recently been shown that an insertion (I)/deletion (D) polymorphism in the ACE gene accounts for variation in serum ACE level. We investigated bronchial responsiveness in patients with sarcoidosis to determine whether it might be associated with ACE gene polymorphism. SUBJECTS: Bronchial responsiveness was assessed in 21 patients with sarcoidosis, 21 patients with asthma, and 18 healthy control subjects. ACE polymorphism was also examined in the 21 patients with sarcoidosis. METHODS: Bronchial responsiveness was measured by recording respiratory resistance with continuous inhalation of methacholine from 49 to 25,000 microg/mL in concentration. The ACE genotype was determined using the polymerase chain reaction. RESULTS: We found a significant increase in bronchial responsiveness in sarcoidosis patients as compared with healthy control subjects (p<0.01). In the sarcoidosis group, patients with the II genotype demonstrated significantly more coughing (p<0.05) and a greater bronchial responsiveness (p<0.05) than did those with DI or DD genotypes. CONCLUSION: Patients with sarcoidosis have increased bronchial responsiveness to some extent, the degree apparently depending on the ACE genotype.

Adult↗
PubMed1997

Distinct roles of mouse laminin beta1 long arm domains for alpha1beta1gamma1 trimer formation.

Mouse embryonal carcinoma F9 cells expressing partial mouse laminin beta1 covering either the C-terminal end (delta beta1S) or the whole (delta beta1L) of the long arm were established to study the assembly and interchain disulfide-bonding of beta1 to endogenous laminin alpha1 and gamma1. Both delta beta1S and delta beta1L were disulfide-bonded to gamma1 but only delta beta1L gamma1 dimer formed a disulfide-bonded alpha1 delta beta1L gamma1 trimer which was actively secreted into the medium. Meanwhile, in the cells producing delta beta1S gamma1 dimer, the level of endogenous alpha1 beta1 gamma1 was reduced but the level of monomeric alpha1 was increased, suggesting that alpha1 was recruited to trimer formation with the delta beta1S gamma1 dimer without disulfide-bonding. This shows that the delta beta1S gamma1 dimer can associate with alpha1 but not support the disulfide-bonding at the N-terminus of the long arm of alpha1. While control cells secrete neither monomeric alpha1 nor the beta1gamma1 dimer into the medium, the delta beta1S gamma1 producing cells probably do as alpha1 delta beta1 gamma1 trimer. We thus propose that the N- and C-termini of the long arm of laminin beta1 have distinct roles for trimer formation.

Animals↗
PubMed1997

Differentiation-dependent expression of laminin-8 (alpha 4 beta 1 gamma 1) mRNAs in mouse 3T3-L1 adipocytes.

We report that laminin-8 (alpha 4 beta 1 gamma 1) is the specific isoform of laminin synthesized in adipocytes. Reverse transcription-polymerase chain reaction (RT-PCR) of mRNA from mouse 3T3-L1 cells with paired primers for alpha 1, alpha 2, alpha 3, alpha 4, alpha 5, beta 1, beta 2, beta 3, gamma 1 and gamma 2 laminins yielded amplified fragments only for alpha 4, beta 1 and gamma 1. A polyclonal antibody against mouse laminin-1 (alpha 1 beta 1 gamma 1) precipitated alpha 4 in addition to beta 1 and gamma 1, while the antibody against a deduced peptide sequence of mouse alpha 4 in addition to beta 1 and gamma 1 in addition to alpha 4. Thus, laminin-8 (alpha 4 beta 1 gamma 1) is the only isoform expressed in 3T3-L1 cells. Northern blots showed that the levels of alpha 4, beta 1 and gamma 1 mRNAs increased 2.5-fold during adipose conversion of 3T3-L1 cells. A 1062 bp cDNA fragment cloned by RT-PCR demonstrated a polymorphism in the mouse alpha 4 gene which would lead to five amino acid changes in the domain G.

3T3 Cells↗
PubMed1997

Expression of the long arm sequence of mouse laminin alpha1, beta1, or gamma1 chain in COS1 cells and assembly of monkey-mouse hybrid laminin.

Mouse laminin alpha1, beta1, or gamma1 sequence covering truncated regions of the long arm was transiently expressed in monkey COS1 cells. Unlike natural laminins, in which only alpha beta gamma trimers are selectively assembled and disulfide-bonded at the long arm, a large fraction of mouse chains formed disulfide-bonded homopolymers. However, a small fraction of mouse beta1 (or gamma1) formed hybrid beta1gamma1 dimers with endogenous monkey gamma1 (or beta1). These hybrid beta1gamma1 dimers formed alpha1 beta1 gamma1 trimer with monkey alpha1. Mouse alpha1 also formed disulfide bonds with monkey beta1gamma1 dimer. Thus, a common mechanism is shared by laminin chains of different animal origins. Sequences in the E8 region at the C-terminal end of the long arm were crucial for this chain-selective assembly. When the C-terminal sequence of mouse beta1 long arm was extended beyond the alpha-loop, the hybrid trimer formation was diminished. This supported the model of altered chain arrangement around the alpha-loop.

Animals↗
PubMed1997

Cloning of cDNAs encoding Bombyx homologues of Cdc2 and Cdc2-related kinase from eggs.

In diapausing eggs of the silkworm Bombyx mori, embryonic cells are arrested at G2 phase. The ability to undertake cell division is resumed in the course of diapause termination caused by such a treatment as acclimation to 5 degrees C. As an initial trial to investigate the relationship between diapause and embryonic cell cycling, we have cloned and sequenced two Bombyx cDNAs encoding two distinct cdc2-related Ser/Thr protein kinases. One (Bm cdc2) encoded a 37.0 kDa protein which had all of the domains characteristic of other Cdc2 kinase. The other (Bcdrk) encoded a 45.1 kDa protein that was most similar to Drosophila and human cdc2-related protein kinases (Dcdrk protein and PISSRLE kinase). Northern blot analysis was carried out to examine levels of Bm cdc2 and Bcdrk mRNA during embryogenesis of non-diapause eggs. The result demonstrated that the mRNA level of Bm cdc2 appeared to correspond to the activity of nuclear/cellular division in non-diapause eggs, and that the developmental profile in the level of Bcdrk mRNA was somewhat different from that of Bm cdc2 mRNA.

Amino Acid Sequence↗