Gene regulation of aldose reductase under osmotic stress.
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Aldehyde Reductase↗
Biomedical subjects
T Iwata
Publications and source records attributed to T Iwata.
Enhancing effect of thoraco-laparotomy on liver metastasis and the role played by active oxygens in its mechanism.
The enhancing effect on liver metastasis produced by the excessive surgical stress of thoraco-laparotomy (TL), and its regulation with a radical scavenger, were studied in 10-week-old Donryu rats. The rats were divided into three groups: those given thoraco-laparotomy for 1 h (the TL group); those given laparotomy alone for 1 h (the L group); those given a short laparotomy (the C group). The effects of treatment with 5 mg/kg of EPC-K1 was assessed in the TL group. A rat hepatocellular carcinoma cell line AH 60C (5 x 10(5) cells) was administered into the portal vein under general anesthesia. The number of metastatic liver nodules was counted 3 weeks later, and the lipid peroxide (LPO) levels of the liver and serum were measured by the TBA method on postoperative days (PODs) 1, 2, and 3. The number of metastatic liver nodules was 40.6 +/- 29.7, 15.0 +/- 15.8, and 13.7 +/- 9.4 in the TL, L, and C groups, respectively. When EPC-K1 was administered to the TL group, the LPO level on POD 1 decreased from 49.8 +/- 25.8 to 18.9 +/- 7.9 nM/g, and the number of metastatic liver nodules decreased from 27.2 +/- 30.0 to 8.9 +/- 12.7 in parallel. The findings of this study suggested that the excessive surgical stress produced by thoraco-laparotomy enhanced liver metastasis in parallel with an increase in LPO levels; however, the radical scavenger EPC-K1 could aid in reversing this effect.
Animals↗
Interleukin-4 production in Epstein-Barr virus-transformed B cell lines from peripheral mononuclear cells of patients with atopic dermatitis.
Interleukin-4 (IL-4) is known as an immunomodulatory cytokine secreted by relatively few cell types, for example, activated T lymphocytes, basophils, and mast cells, but not by B cells. It plays an important role in promoting the production of the IgE antibody. We established Epstein-Barr virus (EBV)-positive B cell lines from peripheral blood mononuclear cells of patients with atopic dermatitis (AD) and tested the production of several cytokines in the cell lines. We found that IL-4 was produced in a cell line, OB, by an IL-4-specific enzyme-linked immunosorbent assay. IL-4 mRNA was detected in OB and two other AD-derived cell lines by IL-4-specific reverse transcription-polymerase chain reaction. IgE was also produced by the OB cells. The production of IL-4 and IgE was enhanced in the cells treated with 12-O-tetradecanoyl phorbol-13-acetate. This is the first evidence that IL-4 is produced by an EBV-transformed B cell line.
B-Lymphocytes↗
Dietary safflower phospholipid reduces liver lipids in laying hens.
This experiment was conducted to determine the effects of dietary safflower phospholipids (crude safflower phospholipid and purified safflower phospholipid) on performance and lipid metabolism of laying hens. Sixty-week-old Single Comb White Leghorn laying hens were divided into four groups of seven birds each, and were given one of four experimental diets containing 5% beef tallow (served as a control, tallow), a mixture of safflower oil and palm oil (SP-oil), crude safflower phospholipid (Saf-PLcrude), or purified safflower phospholipid (Saf-PL) for 7 wk. Egg production ratio and daily egg mass were significantly higher in hens fed Saf-PLcrude diets than in hens of the other diet groups. There were no significant differences in egg weight among groups. Liver cholesterol and triglyceride contents were significantly decreased in all treated groups as compared with the control. The activity of hepatic 3-hydroxy-3 methylglutaryl coenzyme A reductase was the highest in hens fed the Saf-PLcrude diet. Serum esterified cholesterol concentration was decreased by feeding of SP-oil, Saf-PLcrude, or Saf-PL diets. Serum lecithin-cholesterol acyltransferase activity was highest in hens fed the tallow diet. Excreta neutral steroid excretion was significantly increased in the Saf-PLcrude or Saf-PL diet groups, although acidic steroid excretion was not affected by dietary treatments. Total cholesterol, triglyceride, and phospholipid contents in egg yolks were not different for any dietary treatments. The fatty acid compositions of egg yolks from hens fed Saf-PLcrude diets were not different with those fed the SP-oil diet, although eggs of hens fed the Saf-PL diet showed lower total polyunsaturated fatty acids. These results suggest that dietary safflower phospholipids may be a valuable ingredient to layers for reducing liver triglycerides and serum cholesterol without any adverse effects.
Animals↗
Biochemical and molecular characterization of the polyhydroxybutyrate depolymerase of Comamonas acidovorans YM1609, isolated from freshwater.
Comamonas acidovorans YM1609 secreted a polyhydroxybutyrate (PHB) depolymerase into the culture supernatant when it was cultivated on poly(3-hydroxybutyrate) [P(3HB)] or poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] as the sole carbon source. The PHB depolymerase was purified from culture supernatant of C. acidovorans by two chromatographic methods, and its molecular mass was determined as 45,000 Da by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The enzyme was stable at temperatures below 37 degrees C and at pH values of 6 to 10, and its activity was inhibited by diisopropyl fluorophosphonate. The liquid chromatography analysis of water-soluble products revealed that the primary product of enzymatic hydrolysis of P(3HB) was a dimer of 3-hydroxybutyric acid. Kinetics of enzymatic hydrolysis of P(3HB) film were studied. In addition, a gene encoding the PHB depolymerase was cloned from the C. acidovorans genomic library. The nucleotide sequence of this gene was found to encode a protein of 494 amino acids (M(r), 51,018 Da). Furthermore, by analysis of the N-terminal amino acid sequence of the purified enzyme, the molecular mass of the mature enzyme was calculated to be 48,628 Da. Analysis of the deduced amino acid sequence suggested a domain structure of the protein containing a catalytic domain, fibronectin type III module as linker, and a putative substrate-binding domain. Electron microscopic visualization of the mixture of P(3HB) single crystals and a fusion protein of putative substrate-binding domain with glutathione S-transferase demonstrated that the fusion protein adsorbed strongly and homogeneously to the surfaces of P(3HB) single crystals.
3-Hydroxybutyric Acid↗
Staged transsphenoidal surgery for fibrous nonfunctioning pituitary adenomas with suprasellar extension.
Staged transsphenoidal surgery was performed in seven patients with nonfunctioning pituitary adenomas with suprasellar extension. Remnant adenomas were present in a supersellar position after complete removal of the intrasellar tumor, and did not descend into the sella because of the fibrous nature in five patients or fibrous nature and dumbbell shape in two. Magnetic resonance images were obtained every 2 weeks following initial surgery. The suprasellar residual adenomas descended into the sella within 2 months in six patients and 1.5 months in one patient. A second transsphenoidal operation was performed 2 months following the initial procedure in four patients, 3 months in one, and 5 months in two. In six of the seven patients, extensive tumor removal was achieved safely and easily by the staged approach. Patients were followed up over 6 to 58 months (mean +/- SD 24.7 +/- 18.9 months). There were no major surgical complications or recurrence of tumor on follow-up images. Our postoperative imaging studies and surgical results demonstrated that staged transsphenoidal surgery is an effective and safe treatment for fibrous nonfunctioning pituitary adenomas with suprasellar extension.
Adenoma↗
[Effects of eicosapentaenoic acid in patients with bronchial asthma].
Eicosapentaenoic acid (EPA) is composed of 20 unsaturated fatty acids and is similar to arachidonic acid. Epadel, the drug made from EPA, is reported not only to reduce levels of serum lipids, but also to have antiinflammatory and antiallergic effects. EPA may exert these effects via control of the production of prostanoids and leukotrienes. We studied the effects of EPA in patients with bronchial asthma who had hyperlipidemia. The patents were given EPA at 1800 mg/day and they recorded signs and symptoms in an asthma diary during a 2-week observation period and the 8 weeks during which they took the drug. Peak flow, leukotriene B4 concentration in urine, Leukotriene E4 concentration in urine, IgE level, total cholesterol level, and triglyceride level were measured before and after the 8 weeks of medication. Administration of EPA was associated with improvements in symptom score, therapeutic score, asthma score, and peak flow. EPA may be useful in patients with asthma complicated by hyperlipidemia.
Adult↗
Identification of Bruton's tyrosine kinase (Btk) gene mutations and characterization of the derived proteins in 35 X-linked agammaglobulinemia families: a nationwide study of Btk deficiency in Japan.
Deficiencies of Bruton's tyrosine kinase (Btk) have been implicated in the pathogenesis of human X-linked agammaglobulinemia (XLA). The distinctive phenotype observed in B-cell deficiency indicates the crucial role of Btk in B-cell development. This report describes a nationwide study of Btk deficiency in Japan, covering 51 XLA patients (35 independent families). Along with the identification of mutations, the resulting protein products were characterized by an in vitro kinase assay and a Western blot analysis. Thirty-one of the families were found to have mutations in the coding region of Btk. Although mutations were not found in the cDNA of 4 families, the Btk transcripts of these patients were greatly reduced. The identification of several novel missense mutations, in combination with the result of other studies, clarified the presence of two (missense) mutation hot spots, one in the SH1 and the other in the PH domain. The absence of kinase activity seen in 32 of the families underscored the importance of Btk protein analysis as a diagnostic indicator of XLA. The protein analysis also clarified the different effects of missense mutations on kinase activity and protein stability.
Adolescent↗
A new splicing variant in the frog heart sarcolemmal Na-Ca exchanger creates a putative ATP-binding site.
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Adenosine Triphosphate↗
Expression of Na(+)-Ca2+ exchanger with modified C-terminal hydrophobic domains and enhanced activity.
A 6-Kb canine cDNA fragment complementary to the 5' region of the 7-Kb mRNA encoding the cardiac Na+-Ca2+ exchanger was expressed in human kidney 293 cells. The mRNA products were reverse transcribed and amplified by PCR. The determined DNA sequence of the amplified DNA fragments revealed the presence of an intron that was alternatively spliced. The partial exon sequence, located at the 3' end of the 6-Kb cDNA, was alternatively connected to bases 3198, 2821, 2620 and 1844 in four types of splicing products identified. In the largest product the adjoining exon was located after the putative stop codon of the regular sequence. In a second and third type of shortened transcripts, a hydrophobic sequence encoded by the spliced-in exon was linked with the 4th or the 5th extracellular loops, and could possibly replace transmembrane segments 9 or 11. In the fourth type of spliced transcript the in-frame exon sequence introduced one Leu followed by a stop codon in the large hydrophilic loop. Measurements of Ca2+ uptake in 293 cells expressing the modified exchanger indicated a higher activity in comparison with 293 cells expressing the 3.7-Kb cDNA, in which this alternative splicing does not occur. Deletion mutagenesis of the C-terminal region encoded by the spliced-in exon was performed to investigate its role in the enhancement of the transport activity.
Alternative Splicing↗
Structural organization and chromosomal localization of the human ribosomal protein L9 gene.
The intron-containing gene for the human ribosomal protein L9 has been cloned, sequenced and localized. The gene is approximately 5.5 kb in length and contains 8 exons. Splice sites follow the AG/GT consensus rule. The message for human rpL9 is 712 nt in length and is detected in all tissues examined. In the adult, expression is highest in retina and liver while brain shows highest expression among the fetal tissues tested. The transcription start site contains an oligopyrimidine tract, TTCTTTCTT, similar to those found in other ribosomal protein genes. As in other previously characterized ribosomal protein genes, a TATA box is absent from the 5' flanking region but a number of elements recognized by common transcription factors are present including Sp1 sites, CACCC boxes, inverted CCAAT boxes, and GATA elements. Another possible element of interest in the rpL9 5' flanking region is RFX1 also found in the well characterized rat rpL30 promoter. The gene was mapped by fluorescent in situ hybridization to band 13p of chromosome 4. At least 8 possible pseudogenes are present in the human genome, one of which is on Xp. As assessed by Southern 'Zoo-blot' analysis and direct cDNA sequence comparison, the human ribosomal protein L9 gene, like other ribosomal protein genes, is highly conserved among mammals.
Amino Acid Sequence↗
BTKbase, mutation database for X-linked agammaglobulinemia (XLA).
X-linked agammaglobulinemia (XLA) is an immunodeficiency caused by mutations in the gene coding for Bruton's agammaglobulinemia tyrosine kinase (BTK). A database (BTKbase) of BTK mutations has been compiled and the recent update lists 225 entries from 189 unrelated families showing 148 unique molecular events. Each patient is given a unique patient identity number (PIN). Information is included regarding the phenotype including symptoms. Mutations in all the five domains of BTK have been noticed to cause the disease, the most common event being missense mutations. The mutations appear almost uniformly throughout the molecule and frequently affect CpG sites forming arginine residues. A decreased frequency of missense mutations was found in the TH, SH3 and upper lobe of the kinase domain. The putative structural implications of all the missense mutations are given in the database.
Agammaglobulinemia↗
Immunosuppression by anti-ICAM-1 and anti-LFA-1 monoclonal antibodies of free and vascularized skin allograft rejection.
Immunosuppression by anti-adhesion molecule antibody of free or vascularized skin allograft rejection was investigated in rats. Lewis (LEW, RT11) rats were used as donors and Fisher (F344, RT11v1) rats as the recipients. When F344 rats were treated intraperitoneally (i.p.) with anti-intercellular adhesion molecule-1 (ICAM-1) mAb (1A29) (3 mg/kg/day) and anti-leukocyte function-associated antigen-1 (LFA-1) mAb (WT.1) (3 mg/kg/day) one day prior to grafting and daily after grafting for nine days, free skin graft survival was prolonged only slightly compared with that in control rats which were injected i.p. with a daily dose of 6 mg/kg of anti-TNP mAbs (H1-6-2) one day prior to grafting and daily after grafting for nine days. (Mean survival time [MST] of the free skin graft was 11.2 +/- 0.6 days in the control group and 13.4 +/- 0.3 days in the 1A29 + WT-1 treated group [p < 0.01], respectively.) On the other hand, the vascularized graft survival was prolonged significantly in anti-ICAM-1/LFA-1 mAbs-treated F344 rats as compared with that in control rats. (The mean vascularized graft survival time was 14.2 +/- 0.7 days in the control group and 21.5 +/- 1.9 days in 1A29 + WT-1 treated group [p < 0.002]). Our results suggest that interaction with ICAM-1 and LFA-1 is more important in the rejection of vascularized skin allografts than that of free skin allografts.
Animals↗
Clinoidal meningioma arising from falciforme process of optic canal: case report and review.
A 56-year-old female with an initial symptom of unilateral progressive visual disturbance presented with a clinoidal meningioma arising from a falciforme process of the optic canal. Magnetic resonance images with gadolinium-diethylenetriaminepenta-acetic acid demonstrated marked enhancement of a small mass, approximately 1 cm in diameter, roofing the right optic nerve at the intracranial opening of the optic canal. The clinoidal meningioma is rarely reported and the precise originating location of the neoplasm has not been clarified. This is the first case of clinoidal meningioma, which is confirmed by the operative observation as the origin of the neoplasm is a falciforme process of the optic canal. Magnetic resonance images with enhancement are useful for the diagnosis of such a small neoplastic lesion adjacent to bone structure and total removal without a deterioration of visual function is achieved by careful microsurgical procedure.
Animals↗
Prolonged enteral fast with parenteral nutrition decreases PCO2 and flow volume in portal vein: its association with bile secretion.
In an attempt to clarify metabolic events during an enteral fast with parenteral nutrition (PN), changes in blood gas distribution and blood flow in the portal vein, and in bile secretion and hepatic blood flow were investigated in dogs. Dogs were maintained on glucose 25 kcal/kg/day for 7 days. In group I, 8 dogs received orally 10 kcal/kg/day and parenterally 15 kcal/kg/day. In group II, 8 dogs had no oral intake and the total calories were provided by PN for the same interval. On the 7th day, the difference in PCO2 between abdominal aorta and portal vein (A-P DCO2) and the concentration of total bile acids in the bile (TBAC) decreased in group II. The values of A-P DCO2 and TBAC were -5.9 +/- 1.2 mm Hg, 35.4 +/- 9.6 mmol/l in group I and -1.2 +/- 1.0 mm Hg, 18.7 +/- 7.3 mmol/l in group II. These decreases in group II were statistically significant (p < 0.01). Portal venous blood flow significantly decreased in group II, as compared to the levels in group I; however, hepatic blood flow, as estimated by the indocyanine green clearance rate, showed no significant decrease. After the 7-day study in group II, saline containing CO2 at high pressure was administered into the mesenteric vein to achieve gradation of A-P DCO2. Gradation of A-P DCO2 from -1.3 to -5.9 mmHg resulted in an increase in the secretion in TBAC and bicarbonate in the bile from 14.0 to 30.0 mmol/l and from 10.3 to 19.5 mmol/l, respectively. We tentatively conclude that portal hypocapnea plays a role in decreasing bile secretion during the enteral fast with PN administration.
Animals↗
Cardiovascular effect of oral calcium supplementation: echocardiographic study in patients with essential hypertension.
Oral calcium (Ca) supplementation mildly reduces blood pressure. The authors studied the effects of Ca supplementation on the cardiovascular system in patients with mild to moderate essential hypertension. Twelve patients aged forty-nine to seventy years (7 men and 5 women, mean age with 60.3 +/- 7.2 years) participated. The investigators orally administered Ca (1.0 g/day for one week) under hospitalization, adding to a dietary intake of Ca (0.6 g/day). Left ventricular function and systemic arterial compliance were evaluated by M-mode and pulsed Doppler echocardiographies before and after seven days of Ca supplementation. Left ventricular contractility and afterload were not changed. Preload indicated by end-diastolic volume was significantly decreased after Ca supplementation (109.6 +/- 8.5 vs 107.3 +/- 8.2 mL, P < 0.05). Myocardial relaxation evaluated by IIa-mitral valve opening time (87.7 +/- 6.7 vs 82.1 +/- 6.2 ms, P < 0.01) and maximum descending rate of the left ventricular posterior wall (10.6 +/- 1.0 vs 12.4 +/- 1.0 cm/s, P < 0.01), and atrioventricular net compliance assessed by the descending slope of rapid filling flow in the left ventricular inflow tract (2.63 +/- 0.24 vs 2.26 +/- 0.17 m/s2, P <0.05), as well as systemic arterial compliance (2.05 +/- 0.20 vs 2.73 +/- 0.26 mL/mmHg, P < 0.01) were significantly improved by Ca supplementation. Oral Ca supplementation improved the disturbed left ventricular diastolic function and systemic arterial compliance.
Administration, Oral↗
Endothelin receptor antagonist triterpenoid, myriceric acid A, isolated from Myrica cerifera, and structure activity relationships of its derivatives.
As the first non-peptide endothelin receptor antagonist from a higher plant, a new triterpenoid, myriceric acid A (50-235) (1) was isolated from the bayberry, Myrica cerifera. Myriceric acid A (1) inhibited not only an endothelin-1-induced increase in cytosolic free Ca2+ concentration (IC50 = 11 +/- 2 nM) but [125I]endothelin-1 binding in rat aortic smooth muscle cells (Ki = 66 +/- 15 nM). Two new related triterpenoids, myriceric acid C (6), and myriceric acid D (8), were also isolated. Furthermore, the chemical modification of these natural products led to the synthesis of sulfated derivatives (13, 14, 15) which showed 1.5 to 20 times higher affinity for endothelin receptors. The structure activity relationships of myriceric acids and their derivatives are discussed.
Animals↗
Mutations of the Btk gene in 12 unrelated families with X-linked agammaglobulinemia in Japan.
Alterations of the Bruton's tyrosine kinase (Btk) gene are responsible for X-linked agammaglobulinemia (XLA). Although mutations in various regions were reported mainly in the Caucasian population, correlation between the locations of mutation and the clinical phenotypes remains unclear. We report 12 abnormalities of the Btk gene found in 12 unrelated families out of 14 XLA families in Japan and their clinical features. We utilized Southern blotting and single-strand conformation polymorphism (SSCP) analysis. Gene rearrangement in the kinase domain was identified in two patients by Southern blotting. Seven point mutations, two small deletions, and one small insertion were detected by SSCP and sequencing. The SSCP analysis also provided information about the carriers in these families. We found some clinical heterogeneity in the affected family members with the same gene mutation. Moreover, there is considerable inconsistency between the locations of gene aberrations and the immunological phenotypes. Some patients with a nonsense mutation, which may result in the lack of kinase domain, have detectable B cells and immunoglobulins. These identified alterations will provide valuable clues to the Btk protein function and the pathogenesis of XLA.
Agammaglobulinaemia Tyrosine Kinase↗