Search PubMed⌕ Search

Biomedical subjects

S Ikawa

Publications and source records attributed to S Ikawa.

At least 73 records · Page 4Linked to original sources
PubMed1996

Two new members of the murine Sim gene family are transcriptional repressors and show different expression patterns during mouse embryogenesis.

From a cDNA library of mouse skeletal muscle, we have isolated mouse Sim1 (mSim1) cDNA encoding a polypeptide of 765 amino acids with striking amino acid identify in basic helix-loop-helix (89% identify) and PAS (89 % identify) domains to previously identified mSim2, although the carboxy-terminal third of the molecule did not show any similarity to mSim2 or Drosophila Sim (dSim). Yeast two-hybrid analysis and coimmunoprecipitation experiments demonstrated that both of the mSim gene products interacted with Arnt even more efficiently than AhR, a natural partner of Arnt, suggesting a functional cooperativity with Arnt. In sharp contrast with dSim having transcriptional-enhancing activity in the carboxy-terminal region, the two mSims possessed a repressive activity toward Arnt in the heterodimer complex. This is the first example of bHLH-PAS proteins with transrepressor activity, although some genetic data suggest that dSim plays a repressive role in gene expression (Z. Chang, D. Price, S. Bockheim, M. J. Boedigheimer, R. Smith, and A. Laughon, Dev. Biol. 160:315-322, 1993; D. M. Mellerick and M. Nirenberg, Dev. Biol. 171:306-316, 1995). Whole-mount in situ hybridization showed restricted and characteristic expression patterns of the two mSim mRNAs in various tissues and organs during embryogenesis, such as those for the somite, the nephrogenic cord, and the mesencephalon (for mSim1) and those for the diencephalon, branchial arches, and limbs (for mSim2). From sequence similarity and chromosomal localization, it is concluded that mSim2 is an ortholog of hSim2, which is proposed to be a candidate gene responsible for Down's syndrome. The sites of mSim2 expression showed an overlap with the affected regions of the syndrome, further strengthening involvement of mSim2 in Down's syndrome.

Amino Acid Sequence↗
PubMed1996

[Transitions of each inhibitor in a patient with lupus anticoagulant and anti-prothrombin antibody].

In a 2-year-old girl showing purpura on her legs after administration of antibiotics, marked prolongation of activated partial thromboplastin time(APTT) and prothrombin time was noted. Circulating anticoagulants were demonstrated by the failure to correct APTT on neutralization test. A lupus anticoagulant(LA), one of the circulating anticoagulants, was detected by rabbit brain phospholipid neutralization procedure and platelet neutralization procedure. On crossed immunoelectrophoresis, the abnormal prothrombin peaks with reduced electrophoretic mobilities were considered prothrombin/prothrombin-antibody complexes because pretreatment with anti-human IgG serum caused their disappearance. This prothrombin-antibody seemed to be another circulating anticoagulant. The anti-prothrombin-antibody reduced prothrombin activities in the circulating blood of the patient to 20 approximately 30% of normal and the condition persisted for two weeks resulting in the purpura which occurred during that period. After two months, APTT was restored to normal following the disappearance of LA.

Animals↗
PubMed1996

Effect of some sulfonate analogues of ursodeoxycholic acid on biliary lipid secretion in the rat.

The effect of the sulfonate analogues of ursodeoxycholic acid, namely sodium 3 alpha,7 beta-dihydroxy-24-nor-5 beta-cholane-23-sulfonate (norUDC-SO3Na) and sodium 3 alpha, 7 beta-dihydroxy-5 beta-cholane-24-sulfonate (UDC-SO3Na), on biliary lipid secretion was studied in bile fistula rats. During intravenous infusion of the two sulfonate analogues, bile flow and biliary lipid secretion were stimulated in a dose-dependent manner. This suggests that the analogues exert an effect on biliary lipid secretion comparable to that of the naturally occurring bile acid, ursodeoxycholyltaurine (UDC-tau). The effects of norUDC-SO3Na and UDC-SO3Na on bile flow were similar but slightly smaller than that of UDC-tau. The output of bile salts was similar with both sulfonates but greater than that with UDC-tau. The infusion of norUDC-SO3Na or UDC-SO3Na induced cholesterol secretion and phospholipid secretion more significantly than UDC-tau infusion. The increase in phospholipid secretion was particularly pronounced during high-dose administration of norUDC-SO3Na. Although norUDC-SO3Na stimulated cholesterol secretion more intensely than the other two bile salts, it also facilitated phospholipid output, perhaps as a compensatory mechanism, and the biliary cholesterol/phospholipid ratio was decreased to a greater extent by the sulfonates than by UDC-tau. Consequently, the administration of norUDC-SO3Na or UDC-SO3Na produces a more "stable" bile than UDC-tau, suggesting that these sulfonates possess potential cholelitholytic activity.

Animals↗
PubMed1996

An alternative elastase-mediated degradation of fibrinogen and fibrin observed in a patient with herpes simplex encephalitis and pneumonia.

A 74-year-old female developed pneumonia following herpes simplex encephalitis. Her white blood cell counts reached 28,400/microliters, about 90% of which consisted of granulocytes. The polymorphonuclear (PMN) elastase/alpha 1-antitrypsin complex levels increased and reached the maximum of 5,019 ng/ml, indicating the release of a large amount of elastase derived from the granulocytes. The mechanism of PMN elastase release was most likely to be granulocyte destruction associated with phagocytosis. The cleavage of fibrinogen and fibrin by PMN elastase, independent of plasmin, was indicated by the presence of the fragments in immunoprecipitated plasma from the patient corresponding to elastase-induced FDP D and DD fragments and the absence of fragments corresponding to plasmin-induced FDP D and DD fragments on SDS-PAGE. These findings suggested that the large amount of PMN elastase released from the excessive numbers of granulocytes in this patient with herpes simplex encephalitis and pneumonia, induced the cleavage of fibrinogen and fibrin without the participation of plasmin.

Aged↗
PubMed1995

Optimal degree of pulmonary artery banding--adequate circumference ratio to calculated size from normal pulmonary valve dimensions.

These findings suggest that PA banding may be suitable in children with congenital heart disease and excessive pulmonary flow, and that best results are obtained when the band circumference is < 90% of the standard pulmonary valve-ring circumference, as calculated from an equation derived from normal pulmonary valve dimensions. This guideline applies equally well to small infants weighing < 3 kg and to larger patients.

Body Weight↗
PubMed1995

Identification of cellular protein that can interact specifically with the basic helix-loop-helix domain of the aromatic hydrocarbon receptor.

The Ah receptor is a basic helix-loop-helix (bHLH)-PAS protein and functions as a ligand-activated DNA binding protein directly interacting with target genes by binding to xenobiotic responsive elements. We have sought to identify possible cellular proteins that can interact with the Ah receptor. The bHLH domain of the Ah receptor was fused to glutathione-S-transferase (GST), and the resulting fusion protein was used as a probe to help us to identify receptor associated protein(s). At least one such protein, 45kDa (p45), was detected in mouse liver extracts, but it does not bind to the bHLH domain of the Ah receptor nuclear translocator, nor to the transactivation domain of Ah receptor or GST alone.

Animals↗
PubMed1995

Identification of a 120-kDa protein associated with aromatic hydrocarbon receptor nuclear translocator.

The aromatic hydrocarbon receptor nuclear translocator (ARNT) is a basic helix-loop-helix-PAS protein which forms a heterodimer with aromatic hydrocarbon receptor (AHR), this heterodimer mediating the signal transduction in response to the various xenobiotics such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and directly interacting with target genes by binding to xenobiotic responsive elements. An anti-ARNT antibody was raised in rabbits against the bacterially expressed ARNT of amino acids 21-328 from the N-terminal. Using this antibody, besides ARNT itself, we detected at least one protein, 120 kDa, in the immunoprecipitate of anti-ARNT antibodies in HepG2 cells as well as in Hepa-1 cells. However, this protein is not present in the immunoprecipitate of the anti-AHR antisera nor in that of the preimmune sera of the rabbits used for the immunization.

Animals↗
PubMed1995

Spontaneous aortic thrombosis in a neonate with multiple thrombi in the main branches of the abdominal aorta.

Spontaneous aortic thrombosis in the neonate is a rare entity with a high mortality rate. The present patient, who was diagnosed after showing haematuria and cyanosis, underwent aortic thrombectomy with a Fogarty catheter through a left thoracotomy, but died of sepsis, disseminated intravascular coagulation and multiple organ failure. Autopsy revealed multiple residual thrombi in the main branches of the abdominal aorta and necrosis of the abdominal organs despite a patent thoracoabdominal aorta. In patients with no blood flow in the main branches of the abdominal aorta on preoperative examination, removal of thrombi, including those in the main branches of the abdominal aorta, might be performed in a single, early and aggressive procedure.

Aorta, Abdominal↗
PubMed1995

Pulmonary vascular resistance during exercise late after repair of large ventricular septal defects. Relation to age at the time of repair.

Postoperative pulmonary artery pressure and resistance were assessed during exercise in 32 patients late after repair of large ventricular septal defect with pulmonary hypertension. Nineteen patients had a preoperative pulmonary-to-systemic resistance ratio of between 0.15 and 0.50 (group 1) and 13 had a ratio between 0.50 and 0.96 (group 2). Age at the time of operation was 0.9 to 13.0 years (4.6 +/- 3.6) in group 1 and 0.8 to 15.8 years (4.3 +/- 4.2) in group 2. Age at the time of restudy was 9 to 21 years (14.5 +/- 3.0) in group 1 and 9 to 22 years (13.5 +/- 4.1) in group 2. Pulmonary artery pressure was measured in the supine position at rest and during exercise, as were the measurements underlying the calculations of pulmonary vascular resistance. Mean pulmonary artery pressure was 13 to 21 mm Hg (17 +/- 2) and 10 to 26 mm Hg (20 +/- 5) in groups 1 and 2, respectively, at rest, and this increased to 17 to 27 mm Hg (22 +/- 3) and 14 to 39 mm Hg (27 +/- 7) in groups 1 and 2, respectively, during exercise (p < 0.05). Pulmonary vascular resistance was 0.51 to 3.40 U.m2 (1.93 +/- 0.63) and 0.79 to 3.31 U.m2 (2.05 +/- 0.65) in groups 1 and 2 at rest. It was 0.58 to 2.24 U.m2 (1.36 +/- 0.57) and 0.81 to 3.85 U.m2 (2.18 +/- 0.97) in groups 1 and 2 during exercise (p < 0.01). Postoperative pulmonary vascular resistance during exercise correlated well with age at the time of repair in both groups (r = 0.65, p < 0.05 in group 1; r = 0.86, p < 0.001 in group 2). These data suggest that 85% of patients with a preoperative pulmonary-to-systemic resistance ratio of between 0.15 and 0.50 would have normal pulmonary vascular resistance during exercise when operated on at younger than 3.8 years old and 85% of those with a preoperative pulmonary-to-systemic resistance ratio of more than 0.50 would have normal pulmonary vascular resistance during exercise when operated on at younger than 1.1 years.

Adolescent↗
PubMed1995

Assessment of cancer susceptibility in humans by use of genetic polymorphisms in carcinogen metabolism.

Prevention is an important and effective measure for reducing death caused by cancer. Thus information on individual susceptibility to cancer is valuable in suggesting high risk individuals to avoid intake of carcinogenic substances and receive frequent physical screening. To this end, polymorphisms found within cytochrome P450 (CYP) genes implicated in the metabolism of procarcinogens are expected to be good genetic targets in assessing human cancer susceptibility. We have found polymorphisms in the CYP2E1 and CYP1A1 genes associated with lung cancer susceptibility, though there were some discrepancies from observations made by other investigators. Discrepancies among investigators from different regions, however, are very common in these pharmacogenetic studies. We present an explanation for these discrepancies, difficulties associated with prediction of relative risk of individuals, and future directions.

Carcinogens↗
PubMed1995

Effects of bathing in hot water on portal hemodynamics in healthy subjects and in patients with compensated liver cirrhosis.

Bathing in hot water induces vasodilatation of the peripheral vessels and alteration of blood distribution. Using a Doppler flowmeter, we evaluated the effect of bathing in hot water on portal hemodynamics. Eight controls and 8 patients with compensated liver cirrhosis remained immersed in hot water at 42 degrees C for 5 minutes. Portal flow significantly decreased from 811 +/- 141 (ml/min) at the baseline to 530 +/- 98 in the controls and from 855 +/- 308 to 642 +/- 208 in cirrhotics immediately after bathing. This decrease (25%) in cirrhotics was significantly less than that (35%) in controls because vessel diameter did not decrease as rapidly as it did in controls. Portal flow after 30 minutes returned to the baseline values in controls but remained low in cirrhotics. These findings suggest that cirrhotics have a lower hemodynamic response to bathing in hot water compared with that in controls.

Adult↗
PubMed1995

Myxoma of the conjunctiva: a case report and a review of the literature.

A rare case of conjunctival myxoma is reported. A painless tumor was noted in the left bulbar conjunctiva of an 80-year-old woman. The extirpated tumor, 12 x 10 mm, was hypocellular and composed of spindle-shaped or stellate tumor cells. The tumor stroma showed extensive myxomatous changes. Alcian blue stain with hyaluronidase digestion revealed that the matrix contained rich amounts of hyaluronidase-sensitive acid mucopolysaccharides. Immunohistochemically, the tumor cells were positive for vimentin and alpha-smooth muscle actin, suggesting a fibroblastic or myofibroblastic cell phenotype. A review of the literature revealed the rare incidence and invariable benign behavior of conjunctival myxoma.

Actins↗
PubMed1995

[An improved assay for plasma tissue factor activity].

We developed an improved assay for measuring tissue factor activity in plasma with chromogenic substrate (S-2765) which is highly sensitive to factor Xa. In the ordinary assay with S-2222, it was required to prepare the euglobulin fraction of plasma and to heat it, while the improved assay required 20-fold-diluted plasma with Owren's barbital buffer (pH 7.35). The absorbance at 405nm on a colorimeter and human placental tissue thromboplastin preparation (HPT; Thromborel S, Behringwerke AG) was regressed on a semilogarithmic curve. The mean value obtained by this assay for normal subjects was 15.8 +/- 16.4 micrograms/ml HPT (mean +/- 2SD). A correlation of tissue factor activities assayed by the present method and the ordinary method was 0.62. Our data suggest that this improved assay is a useful method for measuring the plasma tissue factor activity.

Adult↗
PubMed1995

Lipoadenofibroma of the uterine corpus. Report of a new variant of adenofibroma (benign müllerian mixed tumor).

This report documents an uncommon case of uterine adenofibroma with a fatty component, for which the term lipoadenofibroma is proposed. Abdominal computed tomography and echography revealed a cystic submucosal lesion in the uterine corpus of a 67-year-old woman. Microscopically, the tumor was composed of benign epithelial cells of a proliferative-endometrial type and nonepithelial stromal cells. The latter mesenchymal elements contained scattered foci of mature adipose cells. The present case is considered to be a new variant of adenofibroma (benign müllerian mixed tumor) of the uterine corpus.

Adenofibroma↗
PubMed1995

[Methicillin-resistant Staphylococcus aureus forming the fried egg appearance colonies isolated from a patient with septicemia].

Slower growing and peculiar colonies, "fried egg" appearance, of different sizes were temporally grown on a sheep blood agar plate from a clinical blood sample obtained from a patient with mediastinitis due to infection by methicillin-resistant Staphylococcus aureus (MRSA) following the graft replacement of thoracic aorta. The organisms revealed morphologically characteristic "fried egg" appearance, mainly Gram-positive cocci including some Gram-negative cells and cell-debris, catalase test positive and coagulase test positive as well as having the identical profiles for S. aureus on biochemical examination with VITEK Systems. The rough surfaced cell walls with unequal thickness of the organisms were observed in an electronmicroscope. According to these bacteriological studies, the organisms were identified as a mutant of S. aureus which had many similarities to staphylococcal L-form. Being resistant to oxacillin, instead of methicillin susceptibility test, and possessing a mecA gene, the organisms were confirmed to belong to MRSA. It is likely that this mutant of S. aureus was induced by a long term medication of sulfamethoxazole-trimetoprim, since the patient had been receiving the drug during 5 weeks when the colonies were first detected.

Aged↗
PubMed1994

Dioxin binding activities of polymorphic forms of mouse and human arylhydrocarbon receptors.

The genetic difference in the susceptibility of mice to environmental toxicities induced by dioxin and related chemicals is governed by polymorphism of the arylhydrocarbon receptor (AhR) (Poland, A., and Knutson, C. (1982) Annu. Rev. Pharmacol. Toxicol. 22, 517-554). cDNA cloning of AhR cDNA from responder (C57BL/6) and non-responder (DBA/2J) mice allowed us to analyze the structure and function of these AhRs. Both of the AhRs, which were expressed in COS-7 cells transfected with their expression plasmids, showed a clear 9 S complex with 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin (TCDD) in a linear glycerol gradient centrifugation, consistent with the result of the endogenously expressed AhR in Hepa-1 cells. This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. Scatchard plot analysis revealed that the dissociation constant (Kd) of C57BL AhR for TCDD is 0.27 nM, while that of DBA AhR is elevated up to six times that high. Chimeric plasmids between the two cDNAs and site-directed mutagenesis revealed two critical alterations responsible for the reduced ligand binding activity: an Ala375 to Val alteration and an elongated carboxyl-terminal sequence due to a T to C mutation at the first letter of the termination codon of C57BL AhR. Two variants with reduced and intermediate ligand binding activity were also found in human AhRs with amino acid alterations equivalent to those of the DBA AhR. Importance of the amino acid at position 381 of human AhR (equivalent to position 375 of mouse AhR) in the ligand binding was confirmed by the fact that the mutation of Val381 to Asp completely abolished the ligand binding activity of human AhR.

Amino Acid Sequence↗