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Biomedical subjects

M Noda

Publications and source records attributed to M Noda.

At least 199 records · Page 11Linked to original sources
PubMed1999

Organotin(IV) compounds as intramolecular transesterification catalysts in thermal depolymerization of poly(L-lactic acid) oligomer to form LL-lactide.

Mono-, di-, and tetraalkyl tin(IV) compounds were evaluated for the intramolecular transesterification reaction of the thermal depolymerization of poly(L-lactic acid) oligomer forming lactide by gas chromatography using a beta-cyclodextrin stationary phase capillary column. The most active catalyst was found to be monobutyltin trichloride (BuSnCl3) (8), which contains tin-halogen bonds, and the least effective was the coordinatively saturated monoorganotin derivative, monobutyltin tris(2-ethylhexanoate) (7). Coordination of the carbonyl group in the oligomer to the tin catalysts is an important factor influencing its activity.

Catalysis↗
PubMed1999

Crystal structure of human serum albumin at 2.5 A resolution.

A new triclinic crystal form of human serum albumin (HSA), derived either from pool plasma (pHSA) or from a Pichia pastoris expression system (rHSA), was obtained from polyethylene glycol 4000 solution. Three-dimensional structures of pHSA and rHSA were determined at 2.5 A resolution from the new triclinic crystal form by molecular replacement, using atomic coordinates derived from a multiple isomorphous replacement work with a known tetragonal crystal form. The structures of pHSA and rHSA are virtually identical, with an r.m. s. deviation of 0.24 A for all Calpha atoms. The two HSA molecules involved in the asymmetric unit are related by a strict local twofold symmetry such that the Calpha atoms of the two molecules can be superimposed with an r.m.s. deviation of 0.28 A in pHSA. Cys34 is the only cysteine with a free sulfhydryl group which does not participate in a disulfide linkage with any external ligand. Domains II and III both have a pocket formed mostly of hydrophobic and positively charged residues and in which a very wide range of compounds may be accommodated. Three tentative binding sites for long-chain fatty acids, each with different surroundings, are located at the surface of each domain.

Binding Sites↗
PubMed1999

Enhancement of the growth of Helicobacter pylori in Brucella broth by hydrogen peroxide.

We found that a sub-lethal concentration of hydrogen peroxide (HPOx) enhanced the growth of Helicobacter pylori in Brucella broth supplemented with 10% fetal bovine serum (BB/FBS). The enhancement was evident at 0.1 mM HPOx and reached a maximun at 3.5 mM. The growth stimulation was dependent on the basal media used; when brain heart infusion broth (BHIB) was used instead of BB, the growth was not altered regardless of the presence or absence of HPOx. Furthermore, the growth in BHIB/FBS was comparable to that in BB/FBS plus 3.5 mM HPOx. This suggested that the enhancement of growth by HPOx resulted from the derepression of the inhibitory factor existing in BB by HPOx. The inhibitory substance seemed to be bisulfite salt since the bacteria grew to a similar extent in bisulfite-less Brucella broth (BLBB0)/FBS compared to the bacterial growth in BHIB/FBS and BB/FBS plus HPOx. These results indicate that the detoxification of bisulfite in BB can be easily achieved by simply adding HPOx to the medium, which causes the oxidation of bisulfite to bisulfate, a less-toxic compound to the bacterial growth. Since we also found that the morphology and cellular protein profile of BB/FBS-cultured bacteria were apparently different from those cultured in BLBB/FBS, we propose that the use of BB for primary isolation and cultivation of H. pylori should be limited on certain occasions, or if necessary, BB can be used after detoxification of the bisulfite by the addition of a low concentration of HPOx.

Bacterial Proteins↗
PubMed1999

Lung cancer in patients under 50 years old.

A long-term retrospective study was carried out on 790 cases of lung cancer to determine if the clinicopathologic characteristics and survival rates of lung cancer patients under the age of 50 differ from those of patients 50 years of age or older at diagnosis by analyzing data on patients registered at Tochigi Cancer Center Hospital. Of the 790 patients, 77 (9.7%) were under the age of 50 at diagnosis. The percentage of women in the younger patient group was significantly higher than that in the older patient group (39.0% vs. 27.5%; P = 0.034). Tumor histology revealed a significant preponderance of adenocarcinomas (60 patients, 77.9%) and a paucity of squamous cell carcinomas (8 patients, 10.4%) in the younger age group (P<0.001). The preponderance of adenocarcinoma was significant in both males and females (male: P = 0.004, female: P = 0.004). Smoking rates and rate of detection by cancer screening did not differ between the two age groups. Because of the paucity of smokers among the younger female patients, causes of lung cancer other than smoking should be sought in younger patients. No difference was found in the stage of the disease at presentation, treatment methods and survival rates between the two age groups. It is suggested that the prognosis for patients with lung cancer under the age of 50 is not significantly worse than for those aged 50 years or older, as has been shown by several investigators.

Adult↗
PubMed1999

Expression of fibroblast growth factor-2 transcripts in the healing of acetic acid-induced gastric ulcers.

Basic fibroblast growth factor-2 (FGF-2) has an important role in angiogenesis, and has been demonstrated to promote ulcer healing. However, the actual part played by FGF-2 in the process of ulcer healing is not well understood. In this study, we investigated expression of FGF-2 transcripts at each stage of gastric ulcer healing, using an acetic acid model in rats. We made ulcers in the rat stomach by direct application of acetic acid, and 3 days and 1, 2, 3, 4, 8 weeks after treatment, we examined expression of FGF-2 transcripts by in situ hybridization. On day 3, FGF-2 transcripts were detected in mononuclear cells infiltrating the submucosal layer around the ulcer. After 1 and 2 weeks, expression of FGF-2 transcripts was prominent in spindle-shaped mesenchymal cells and endothelial cells, which proliferated in the ulcerative region. Some of the spindle-shaped cells which expressed FGF-2 transcripts also showed immunoreactivity for alpha-smooth muscle actin. After 3 and 4 weeks, FGF-2 expression was seen mainly in endothelial cells of vessels. These results suggest that different cells produce FGF-2 during the process of gastric ulcer healing, and some of the spindle-shaped cells expressing FGF-2 transcripts in the early phase are myofibroblasts.

Acetates↗
PubMed1999

Impairment of transalveolar fluid transport and lung Na(+)-K(+)-ATPase function by hypoxia in rats.

We examined whether hypoxic exposure in vivo would influence transalveolar fluid transport in rats. We found a significant decrease in alveolar fluid clearance of the rats exposed to 10% oxygen for 48 h. Terbutaline did not stimulate alveolar fluid clearance, and alveolar fluid cAMP levels were lower than those determined in normoxia experiment. Hypoxia did not influence the alveolar fluid lactate dehydrogenase levels, Evans blue dye fluid-to-serum concentration ratio, or lung wet-to-dry weight ratio, indicating no significant change in the permeability of alveolar-capillary barrier. Histological examination showed no significant fluid accumulation into the interstitium and the alveolar space. Hypoxia did not reduce lung ATP content; however, we found significant decrease in Na(+)-K(+)-ATPase hydrolytic activity in lung tissue preparations and isolated alveolar type II cells. Our data indicate that hypoxic exposure in vivo impairs transalveolar fluid transport, and this impairment is related to the decrease in alveolar epithelial Na(+)-K(+)-ATPase hydrolytic activity but is not secondary to the alteration of cellular energy source.

Adenosine Triphosphate↗
PubMed1999

A novel compound heterozygous mutation in the steroidogenic acute regulatory protein gene in a patient with congenital lipoid adrenal hyperplasia.

Congenital lipoid adrenal hyperplasia (CLAH) is an autosomal recessive disorder characterized by impaired synthesis of all adrenal and gonadal steroid hormones. Recently, it was reported that mutations in the steroidogenic acute regulatory protein (StAR) gene cause CLAH. In the present study, we have analyzed the StAR gene of a Japanese patient with CLAH. PCR amplification and subsequent nucleotide sequencing of the StAR gene and those of her parents revealed that the patient has a compound heterozygous mutation of this gene. In one allele, an undescribed G to C transversion in codon 217, which occurred at the last base of exon 5 and thus altered the splice donor site sequence, apparently resulted in a substitution of Arg to Thr (AGG to ACG: R217T), and in the other allele, a C to T transition in codon 218 caused a substitution of Ala to Val (GCG to GTG: A218V), which has been previously shown to abolish StAR activity. In vitro expression analysis of an allelic minigene that consists of exons 4-6 of the R217T mutant StAR gene showed that the G to C transversion in the splice donor site of exon 5 caused by the R217T mutation disrupts normal splicing, resulting in the complete skipping of exon 5, which alters the translation reading frame of exon 6, introduces a stop codon at amino acid position 174, and thus impairs the activity. A functional expression study of the R217T replacement mutant revealed that the mutant has no steroidogenesis-enhancing activity if the transcript of the R217T mutant allele is ever spliced normally and translated into the protein. From the genetic analysis of 50 healthy subjects, the novel R217T mutation was unlikely to be due to polymorphism. Together, these results indicate that this patient is a compound heterozygote for the mutation in the StAR gene (T217R and A218V) and that these mutations inactivate the StAR function and give rise to clinically manifest CLAH.

Adrenal Hyperplasia, Congenital↗
PubMed1999

[The relationship among subjective symptoms of fatigue, subjective fatigue feeling, and life habits of high school and college students].

The relationship among subjective symptoms of fatigue, subjective fatigue feeling, and life habits of high school and college students. The purpose of this study was to examine the relationship among subjective symptoms of fatigue (SSF), subjective fatigue feeling (SFF), life habits (behavioral patterns (BP) and life-style consciousness (LC)) in male students. A questionnaire on SSF, SFF, fatigue content, BP and LC was administered to 1802 male students aged 15-20 yr, and data from 1792 properly completed questionnaires was analyzed. The results were: 1) Students experience high SFF from daily activity. Students with a higher SFF tend to have more complaints of SSF, especially symptoms of languor, but the relationship between SFF and symptoms of irritation and physical disintegration are low. 2) Relationships between SFF and BP and LC are relatively low, except for physical condition. Even if the BP is successful, student's SFF is relatively high. 3) Subjective degree of health and physical condition relate highly to SSF. Exercise habits relate to loss of vigor, dietary habits to languor, loss of vigor, drowsiness and a decrease in concentration, and LC to SSF except for languor. It was inferred that SSF is influenced by BP and LC.

Adolescent↗
PubMed1999

Coordinated expression of noggin and bone morphogenetic proteins (BMPs) during early skeletogenesis and induction of noggin expression by BMP-7.

Coordinated regulation of the activities of bone morphogenetic protein (BMP) and its inhibitors is essential for skeletal development since loss-of-function experiments show that both BMPs and BMP inhibitory signals, such as noggin, are required to establish proper formation of skeletal tissues. In this paper, we asked how and when noggin would be functional to interact with BMPs during skeletogenesis in mammals. For this purpose, we first analyzed the spatial and temporal patterns of noggin, BMP-2, BMP-4, and BMP-7 expression during early skeletogenesis in mouse embryos. In situ hybridization study revealed that noggin expression was detected at a low level in limb mesenchyme, whereas BMP-7 was expressed at a high level throughout limb mesenchyme 10.5 days postcoitum (dpc) in mouse embryos. One day later, noggin mRNA was expressed at a high level in the prechondrogenic condensations in appendicular and axial skeletal primordia, where sox9 transcripts were also expressed. At this stage, noggin-expressing cells were surrounded by those expressing BMP-7. The chondrogenic cell condensation continued to express noggin transcripts in 12.5 dpc and 13.5 dpc embryos, and again the noggin-expressing cells within the cartilaginous tissue were surrounded by those expressing BMP-7. We further examined interaction of noggin and BMPs by using organ cultures of 11.5 dpc mouse forelimbs and found that implantation of carriers containing BMP-7 protein into the forelimb explants induced noggin expression in the limb mesenchyme. BMP-7 also induced type II collagen and sox9 mRNAs in the same cell population, indicating that noggin induction occurred in the chondrogenic precursor cells. BMP-7 effects on noggin expression were observed in a dose-dependent manner within a dose range of 10-100 ng/microliter. These results suggest that BMP-7 induced expression of noggin transcripts within skeletal cell condensation and that this noggin expression in turn could act antagonistically to attenuate BMP action in the early skeletogenesis.

Animals↗
PubMed1999

Oncogene-mediated downregulation of RECK, a novel transformation suppressor gene.

The RECK gene was initially isolated as a transformation suppressor gene encoding a novel membrane-anchored glycoprotein and later found to suppress tumor invasion and metastasis by regulating matrix metalloproteinase-9. Its expression is ubiquitous in normal tissues, but undetectable in many tumor cell lines and in fibroblastic lines transformed by various oncogenes. The RECK gene promoter has been cloned and characterized. One of the elements responsible for the oncogene-mediated downregulation of mouse RECK gene is the Sp1 site, where the Sp1 and Sp3 factors bind. Sp1 transcription factor family is involved in the basal level of promoter activity of many genes, as well as in dynamic regulation of gene expression; in a majority of cases as a positive regulator, or, as exemplified by the oncogene-mediated suppression of RECK gene expression, as a negative transcription regulator. The molecular mechanisms of the down-regulation of mouse RECK gene and other tumor suppressor genes are just beginning to be uncovered. Understanding the regulation of these genes may help to develop strategies to restore their expression in tumor cells and, hence, suppress the cells' malignant behavior.

Animals↗
PubMed1999

Cytotoxicity and mutagenicity of UVB assessed using cultured rat fibroblast.

A retroviral vector carrying both positive (neo) and negative (herpes simplex virus thymidine kinase or HSV-tk) selection markers was constructed as a substrate for mutational assay in mammalian cells. Using a population of rat fibroblast cells carrying a single copy per cell of retroviral DNA randomly integrated in their chromosomes, we examined the cytotoxic and mutagenic activities of ultraviolet light (UV) at four wavelengths (254, 290, 300, and 320 nm). The action spectra for these activities are similar to some of the previously reported spectra for photochemical DNA modifications, erythema, cell killing, and mouse skin carcinogenesis, except at 290 and 320 nm. At 290 nm, no significant mutagenicity was observed. At 320 nm, both cytotoxic and mutagenic activities were 10 times higher than the values expected from the absorption spectrum for DNA and the action spectrum for bacterial inactivation and mutagenesis. Structural comparison of some of the HSV-tk mutants obtained after irradiation with 300 and 320 nm UV revealed partially different patterns of mutation specificity, suggesting the involvement of multiple molecular mechanisms in the genotoxicity associated with this range of UV.

Animals↗
PubMed1999

Identification of the docked granule pool responsible for the first phase of glucose-stimulated insulin secretion.

The mechanisms underlying the first phase of glucose-stimulated insulin release, the deterioration of which marks the early stages of both type 1 and type 2 diabetes, are essentially unknown. Among many hypotheses, one holds that the first phase is due to a readily releasable pool of insulin-containing granules. We used current knowledge of the mechanisms of exocytosis and the proteins involved in docking granules at the plasma membrane to test this hypothesis. A docked pool of readily releasable granules was identified by immunoprecipitation of the plasma membrane protein syntaxin with a specific antibody and by co-immunoprecipitation of soluble N-ethylmaleimide-sensitive factor attachment protein-25 (SNAP-25) and the granule proteins synaptobrevin and synaptotagmin. The four SNARE proteins co-immunoprecipitated each other, thus identifying the core complex associated with docked granules. Using co-immunoprecipitation as a marker for docked granules, we found that the docked pool was rapidly discharged during the first phase of glucose-stimulated insulin release and refilled during the second phase. Other secretagogues also released the pool, whereas the physiological inhibitor norepinephrine blocked its release. Further studies on the nature of this pool of granules should shed light on the causes of its deterioration in the early stages of diabetes and the reasons for deficient insulin release.

Animals↗
PubMed1999

Intact alveolar epithelial permeability and transalveolar fluid absorption after thoracic irradiation in rats.

We have addressed the question of how the alveolar space stays relatively free of fluid when thoracic irradiation injures the pulmonary capillary endothelium and plasma fluid leaks into the interstitium. A single dose of 15 Gy to the thorax of rats significantly increased the pulmonary capillary filtration coefficient and the lung wet/dry weight ratio 2 h after irradiation. However, there was no significant increase in the release of lactose dehydrogenase or leaking of Evans blue dye into the alveolar space, indicating that alveolar epithelial permeability remained intact. We found no significant difference in the basal alveolar fluid clearance between control and irradiated animals. There was also no significant difference in blockage of alveolar fluid clearance by amiloride. This indicates that the function of the alveolar epithelial Na(+) channels is not impaired and that alveolar epithelium absorbs fluid normally. Examination of lung tissue by light microscopy demonstrated accumulation of fluid in the perivascular region but not in the alveolar space. Our data appear to indicate that the alveolar epithelial barrier function is more resistant to radiation than that of the pulmonary capillary endothelium. We conclude that intact alveolar epithelial permeability and normal transalveolar epithelial fluid absorption ability are of critical importance in keeping the alveolar space relatively free of fluid during acute radiation lung injury.

Animals↗
PubMed1998

Smad2 overexpression enhances Smad4 gene expression and suppresses CBFA1 gene expression in osteoblastic osteosarcoma ROS17/2.8 cells and primary rat calvaria cells.

Mothers against decapentaplegic-related proteins (Smads) are essential intracellular components for the signal transduction of transforming growth factor-beta (TGF-beta) family members. Smad1 mediates bone morphogenetic protein (BMP) signals, whereas Smad2 functions downstream of TGF-beta. TGF-beta is expressed in osteoblastic cells and acts as an autocrine and/or paracrine factor in regulation of osteoblastic functions. In this study, we examined the levels and functions of Smad2 in osteoblastic cells. Smad2 mRNA expression was hardly detectable by Northern blot analysis in an osteoblast-like cell line, ROS17/2.8, as well as in primary rat calvaria (PRC) cells. Overexpression of Smad2 gene enhanced endogenous Smad4 gene expression in both ROS17/2.8 and PRC cells, while Smad3 levels were not altered. Smad2 overexpression suppressed osteocalcin mRNA expression in ROS17/2.8 cells. Furthermore, Smad2 overexpression also suppressed transcriptional activity of the 1-kilobase pair osteocalcin gene promoter, which was linked to chloramphenicol acetyltransferase reporter gene in both ROS and PRC cells. Since core binding factor A1 (CBFA1) is involved in osteocalcin gene expression, we further examined CBFA1 expression in the Smad2-overexpressing ROS17/2.8 and PRC cells. The levels of CBFA1 mRNA were suppressed by the overexpression of Smad2 by about 50% in both ROS17/2.8 and PRC cells. TGF-beta treatment enhanced Smad4 expression in PRC cells, and this TGF-beta effect was blocked by the cotreatment with BMP, indicating that TGF-beta signaling pathway is interfered by BMP. These data indicate that Smad2 regulates Smad4 specifically and that CBFA1 gene is one of the downstream targets of Smad2.

Animals↗