Search PubMed⌕ Search

Biomedical subjects

S Ikawa

Publications and source records attributed to S Ikawa.

At least 91 records · Page 5Linked to original sources

Hemostatic studies in patients with carbohydrate-deficient glycoprotein syndrome.

The carbohydrate deficient glycoprotein (CDG) syndrome is a newly described disorder characterized by impaired glycosylated molecules. It has been reported that transient stroke-like episodes appear in half of the patients. We performed hemostatic studies on three CDG syndrome patients belonging to two unrelated families. The most characteristic findings were decreases in antithrombin III (AT III), protein C and alpha 2 plasmin inhibitor to nearly half normal levels. Protein S was reduced in two (siblings) patients. Isoelectric focusing of AT III in native plasma revealed decreased intensity of the major band and increased intensity of a minor cathodal band. These minor AT III molecules were considered to lack an oligosaccharide sidechain. A 12-year-old girl defective not only for AT III but also protein C and protein S developed disseminated intravascular coagulation accompanied by arterial thrombosis in her left hand following dyspnea associated with bronchial asthma. These findings suggest that thrombotic predisposition in patients with CDG syndrome is due to decreased levels of major coagulation inhibitors, particularly as a result of impaired glycosylation of AT III.

Adolescent↗

A chimeric RecA protein exhibits altered double-stranded DNA binding.

RecAc38 protein, a chimeric RecA protein of Escherichia coli and Pseudomonas aeruginosa, is proficient in the renaturation from complementary single strands. However, RecAc38 protein showed a significant deficiency in promoting homologous pairing of single-stranded DNA and double-stranded DNA. RecAc38 protein was able to remove the secondary structure of single-stranded DNA, the first step of homologous pairing, at a slightly reduced rate. RecAc38 protein-single-stranded DNA-complex (presynaptic complex) was found to be deficient in the sequence-independent binding to double-stranded DNA which is a step in the search for the homology. On the other hand, once unwinding was initiated, RecAc38 protein was able to propagate the unwinding of the double helix at the same extent as wild-type RecA protein. These defects and the proficiency of RecAc38 protein are explained by a model showing that RecA protein has three distinct DNA strand-binding sites (a site for the primary binding to single-stranded DNA, a site for the binding to a strand of second single- or double-stranded DNA, and a site required for the binding to the other strand of the double-stranded DNA) and that RecAc38 protein has a defect in the third site.

Adenosine Triphosphatases↗

Open heart operation in a young child with spherocytosis.

Open heart operations on patients with hereditary spherocytosis have been reported rarely. Young children who have not yet undergone splenectomy have a high risk of intraoperative hemolysis because of the heart-lung machine and secondary renal failure. We report the case of a 15-month-old child with spherocytosis who underwent an open heart operation without serious complications as a result of careful and appropriate perioperative management.

Ductus Arteriosus, Patent↗

Effects of daily mild supine exercise on physical performance after 20 days bed rest in young persons.

To investigate the effects of daily mild supine exercise on physical performance capacity identified as maximal oxygen uptake rate (VO2max) after 20 days bedrest, 3 male students performed a supine pedaling at 40% intensity of VO2max for one hour every day, while 6 male and 5 female students were control. Before and after the bedrest, muscle mass and strength of exercising leg and cardiovascular responses during -40mmHg lower body negative pressure (LBNP) and moderate upright cycling exercise were measured. Despite the exercise programme VO2max was similarly decreased to the control subjects after bed-rest. The delta VO2max was correlated to delta % left ventricular fractional shortening during LBNP, and also % delta VO2max to % delta stroke volume of the moderate exercise (both p<0.05). The exercise programme should be too weak to maintain cardiovascular functions and thus to present the decrease in VO2max against prolonged bedrest as well as weightlessness stress.

Adult↗

Characterization of hamster CYP1A1 gene: inducible expression and negative regulation.

A genomic clone encoding the hamster CYP1A1 gene was isolated from a hamster EMBL-3 genomic library and characterized. The CYP1A1 gene contained seven exons including the noncoding first exon as determined for CYP1A1 of other species. DNA sequence analysis up to -2307 bp of the CYP1A1 gene revealed the occurrence of five consensus xenobiotic responsive elements (XREs) and one basal transcription element (BTE) in addition to the canonical TATA box. For functional analysis, transfection experiments were performed in human hepatoma HepG2 cells with reporter gene constructs consisting of fragments with various lengths of the 5'-flanking region of the CYP1A1 gene and bacterial chloramphenicol acetyltransferase (CAT) gene. External deletion of the upstream region from the reporter gene resulted in a stepwise decrease of the CAT activity, suggesting that XREs were responsible for inducible expression of CYP1A1 gene by 3-methylcholanthrene (MC). A negative regulatory element (NRE) was also identified in the 5'-flanking region at -833 to -642. Removal of the NRE from the CYP1A1-CAT fusion gene resulted in about 3-fold increase of MC-inducible CAT activity. Using gel retardation assays with HepG2 nuclear extract, we demonstrated the presence of a specific protein which bound to the NRE fragment. Further competition analysis and methylation interference assays revealed that the nuclear protein bound to a 22-base fragment (from -688 to -709) of the NRE region, whose sequences were conserved among hamster, human, and rat CYP1A1 genes.

Animals↗

Restriction fragment length polymorphism of the human CYP2E1 (cytochrome P450IIE1) gene and susceptibility to lung cancer: possible relevance to low smoking exposure.

Polymorphic metabolism of certain chemical carcinogens may result in differences in susceptibility to cancers. Human CYP2E1 (cytochrome P450IIE1) is an enzyme involved in the metabolic activation of precarcinogens such as nitrosamines. We detected a restriction fragment length polymorphism (RFLP) of the human CYP2E1 gene for the restriction endonuclease Dra I. The distribution of this polymorphism was examined among lung cancer patients (n = 91), patients with cancer of the digestive tract (n = 45) and controls (n = 76). A significant difference in the distribution was observed between lung cancer patients and controls (chi 2 = 11.4 with 2 df; p < 0.005). On the other hand, there was no significant difference between patients between cancer of the digestive tract and controls (chi 2 = 4.87 with 2 df; NS). This finding suggests that the Dra I polymorphism of the CYP2E1 gene is associated with susceptibility to lung cancer. In addition, an association was found between the amount of lifelong smoking exposure and the distribution of the genotypes of the RFLP among lung cancer patients. The distribution pattern seemed deviated from that of controls especially in the population of low smoking exposure. Our Northern blot analysis data using RNA from human liver autopsy samples suggest that the Dra I polymorphism might be associated with the gene expression of CYP2E1 at mRNA level.

Aged↗

A complete structure of the mouse Ah receptor gene.

A complete sequence of the Ah receptor gene was cloned from a mouse genomic library by using the Ah receptor cDNA as a probe. The Ah receptor gene is 37.5 kb long and is split into 11 exons by 10 introns. Sequence analysis of the 5' flanking region of the Ah receptor gene reveals that there is neither a TATA box nor a CAAT box in the promoter region. Instead, this gene has a few GC boxes and other enhancer elements in the 5' upstream flanking region. Southern blot analysis indicated that the Ah receptor gene is a unique gene.

Animals↗

Aberrant CYP1A1 induction: discrepancy of CYP1A1 mRNA and aryl hydrocarbon hydroxylase activity in mutant cells of mouse hepatoma line, Hepa-1.

We have isolated new benzo[a]pyrene-resistant clones, cl-21 and cl-32, of the mouse hepatoma line, Hepa-1. CYP1A1-dependent aryl hydrocarbon hydroxylase activity is not inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin or 3-methylcholanthrene in these two cell lines. However, mRNA of CYP1A1 is inducible in cl-21 and cl-32 cells, as in the wild-type cells, in spite of an undetectable level of cytosolic Ah receptor. The cl-21 cDNA of Cyp1a-1 was found to have a single mutation leading to an amino acid substitution from Leu (118) to Arg (118). However, the CYP1A1 protein band was not detected on Western immunoblots. The cDNA of cl-32 was found to have a single mutation leading to an amino acid change from Arg (359) to Trp (359). The presence of the mature protein in cl-32 was confirmed by Western blot analysis. Somatic cell hybridization experiments demonstrated that the phenotype of cl-21 and cl-32 is recessive and that these clones belong to the same complementation group. These data suggest that there may be a non-Ah receptor-mediated mechanism of CYP1A1 induction.

Animals↗

Crystalloid granuloma of the parotid gland: a case report.

A case of an uncommon granulomatous lesion of the parotid gland is presented. A tumorous lesion was pointed out in the upper left neck region of a 63 year old Japanese female and then extirpated. Histologically, the tumor arose in the parotid gland and showed a chronic granulomatous lesion with lymphocytes and histiocytic cells, including the multinucleated foreign body type. In addition, numerous so-called crystalloids were deposited throughout the lesion. The crystalloids were partially positive on von Kossa's stain and nonbirefringent under polarized light. To the authors' knowledge, this is the second reported case of crystalloid granuloma of the parotid gland since the first one was described by Takeda in 1991.

Crystallization↗

Regional changes in muscle mass and strength following 20 days of bed rest, and the effects on orthostatic tolerance capacity in young subjects.

To this day, many studies have suggested that prolonged bed rest (BR) affects on muscle mass and strength not only in gravity muscles but also in ungravity muscles. However, it is still unclear whether the decrease in regional muscle strength after BR is due to the alterations in the corresponding muscle mass, or not. On the other hand, if BR decreases the mass of antigravity muscles (UGM) as well as muscle strength and then increases tissue compliance of the antigravity muscles, orthostatic tolerance capacity will be decreased by the reduction in cardiac output (CO) in spite of the increase in myocardial contractility because the more decrease in venous return due to the more increase in blood pooling within the compliant tissues of the lower body. However, this is also unclear. To make these questions clear, the present study investigated the regional muscle mass and strength and orthostatic tolerance capacity before and after 20 days of bed rest in young subjects.

Adult↗

[Reoperation and balloon dilatation for stenosed xenograft valved conduits].

Follow-up has been achieved in 41 hospital survivals who received xenograft valved conduits in the pulmonary position. The interval after operation ranged 6 months to 13 years (average 5.2 +/- 3.7 years) (+/- standard deviation). There has been 8 late deaths, 3 of which were sudden. Of the 11 reoperations, 7 underwent graft replacement with no operative death. The actuarial reoperation free survival rate was 73% at 5 years, and 54% at 10 years. There was a significant correlation between the interval after operation (x years) and the pressure gradient across the conduits (y mmHg). (y = 20.7 + 9.7x, r = 0.74, p < 0.001). Balloon dilatation of the conduits was performed in 15 patients. The mean conduit gradient was significantly (p < 0.001) reduced from 85 +/- 29 to 54 +/- 22 mmHg. However, the effect was not satisfactory enough and 4 patients received graft replacement after the balloon dilatation. These results warrant the avoidance of xenograft valved conduits in the pulmonary position, the safety of the graft replacement, and the limitation of the balloon dilatation for the stenosed conduits.

Adolescent↗

Bone turnover and calcium metabolism during 20 days bed rest in young healthy males and females.

Bone is a dynamic tissue that functions not only as a mechanical support, but also as a major component of the metabolic and endocrine systems maintaining mineral homeostasis. It has been shown that immobilization induces decalcification of bone. To evaluate the effect of immobilization on bone mineral density and calcium metabolism, we investigated 9 young healthy males and females during 20 days bed rest. Three methods for measuring bone mineral density were performed to quantify whole body and regional bone changes: 1) dual energy X-ray absorptiometry, 2) quantitative computed tomography, and 3) multiple scanning X-ray photodensitometry, respectively. Bone mineral density showed a rapid decreasing tendency, especially in both lumbar and metacarpal bones (mean +/- SE: 4.6 +/- 0.6% and 3.6 +/- 0.4%, respectively). Urinary daily excretion of deoxypyridinoline, a sensitive marker of bone matrix resorption, tended to increase by day 10, and to decline by day 20 (mean +/- SE: 42.2 +/- 1.4, 27.6 +/- 2.2 nmol day-1, respectively). However, neither alkaline phosphatase nor tartrate-resistant acid phosphatase, both markers of osteoclast and mature osteoblast function, changed. These results showed that in the early stage of immobilization, bone matrix might be resorbed without any activation of osteoclasts, resulting in rapid decalcification of vertebral and cortical bones without any discernible changes in anatomical structure.

Absorptiometry, Photon↗

Effects of 10 and 20 days bed rest on leg muscle mass and strength in young subjects.

Sedentary voluntary students were exposed to 10 (n = 8) and 20 (n = 14) days bed rest to study effects of prolonged bed rest on isometric strength of knee extension and flexion, total leg strength, right hand grip and elbow flexion using different dynamometers. Further, muscle mass of right leg and arm was measured by dual energy X-ray absorptiometry, and cross sectional area of right thigh by X-ray computed tomography before and after bed rest and after 4 or 8 weeks of recovery. After 10 days bed rest, these variables tended to decrease except for the muscle mass of right arm which increased. After 20 days of bed rest, a similar trend was observed, but at a statistically significant level of p < 0.05. However, no correlation was observed between the decrease in knee extensor strength and cross sectional area of the thigh. Nor was a correlation observed between the sum total of isometric strength of the leg and the total muscle mass measured. The 24h urinary excretion of N2 and creatinine was not changed through the experiments. During recovery, the variables measured had reached the initial levels after 4 or 8 weeks. These changes were not affected by mild supine exercise training. The results suggest that isometric muscle strength was decreased in non-antigravity muscles as well as antigravity muscles by prolonged bed rest, but the rate of changes did not correlate to the corresponding changes in muscle mass. The decreases in maximum voluntary strength are probably not only due to the decrease in muscle mass but also due to reductions of neuromuscular function.

Absorptiometry, Photon↗

[Evaluation of a latex agglutination assay method for the determination of plasmin/alpha 2 plasmin inhibitor complex].

We evaluated a latex agglutination assay method for concentration of plasmin/alpha 2 plasmin inhibitor complex (PPI) developed recently. The latex reagent consisted of two kinds of latex particles, one was coated with monoclonal antibody against plasmin (JIPPI-3) and another coated with monoclonal antibody against modified alpha 2 plasmin inhibitor (JIPPI-50). A correlation of concentrations of PPI between this method and ordinary EIA kit was very good (r = 0.969). Within-run precision of latex agglutination reagent also was good. The concentrations of PPI in plasmas of 40 in 43 normal subjects were 0-0.8 microgram/ml and others were 0.8-1.6 microgram/ml. Plasma levels of PPI were markedly elevated in patients with DIC. In addition, half of the patients with malignant tumors or liver diseases had increased levels of PPI. 16 of 32 cases with selected diseases (18 malignant tumors, 4 liver diseases, 2 infectious diseases, 2 cerebral contusions, 6 others) showed abnormal levels in PPI (> or = 0.8 microgram/ml) during several days preceding the elevation of FDP. It suggested that PPI could reflect fibrinolysis earlier than FDP. This latex agglutination assay is a simple and rapid method, and specific for the determination of PPI concentration as well as EIA method. We conclude that this assay method is very convenient for clinical use.

Antifibrinolytic Agents↗

[Growth of the hypoplastic aortic arch after arch repair for coarctation and interruption of the aorta].

Surgical treatment for a hypoplastic aortic arch associated with coarctation or interruption of the aorta is controversial. We evaluate the changes of diameter of proximal transverse aortic arch after surgery in 28 patients. Proximal transverse aortic arch in all patients was preoperatively 3.5 +/- 0.9 mm (2.5 to 7 mm), and 54 +/- 12% (36 to 84%) to the normal aortic valve dimension (n-AVD: 16.6 X BSA0.6). While postoperative proximal transverse aortic arch was 6.5 +/- 1.8 mm, and 76 +/- 12% to the n-AVD, and significantly grew more than the preoperative arch dimension (p = 0.0001). In 18 patients having two times cardiac catheterization postoperatively, proximal transverse aortic arch was 6.5 +/- 1.6 mm, and 75 +/- 13% to n-AVD on the 1st postoperative examination. On the 2nd examination, the arch was 9.9 +/- 1.9 mm, and 88 +/- 12% to n-AVD, and significantly grew with increasing years (p < or = 0.0003). We concluded that the proximal transverse aortic arch, which was more than 36% to n-AVD in diameter, if not dilated surgically, grew with increasing years after aortic arch repair.

Aorta, Thoracic↗

[Subaortic stenosis in coarctation or interruption of the aorta--changes of left ventricular outflow tract dimension after aortic arch repair and pulmonary artery banding].

Left ventricular outflow tract (LVOT) dimension was measured in seven patients with coarctation (CoA) or interruption (IAA) of the aorta before and after aortic arch repair and pulmonary artery banding. The age of patients ranged 3 to 69 (mean 16) days, the weight 3.0 to 3.9 (mean 3.4) kg. Associated cardiac anomalies were VSD in 6, MA and DORV in 1. In five patients compared by ultrasound, preoperative LVOT dimension ranged from 3.5 to 5.0 (mean 4.4) mm with the ratio to the normal aortic valve dimension (n-AVD; 16.6 x BSA0.6) from 54 to 82 (mean 69)%. Postoperative dimension increased 5.0 to 7.4 (mean 5.7) mm and the ratio to the n-AVD increased 65 to 89 (mean 80)%. In three patients compared by LV graphy, preoperative LVOT dimension ranged from 4.0 to 4.5 (4.2) mm and the ratio ranged from 61 to 72 (68)%. Postoperative dimension increased from 4.5 to 6.7 (5.3) mm, and 74 to 80 (78)% to n-AVD after operation. Postoperative pressure gradients between LV and ascending aorta in each patient were 1 to 9 (mean 6) mmHg. In any patients, LVOT obstruction did not advance after aortic arch repair and pulmonary artery banding.

Aorta↗

Mixed type of total anomalous pulmonary venous connection with hemi-pulmonary vein atresia.

This reports a successfully corrected case of an 8-day-old baby who had a rare mixed type of total anomalous pulmonary venous connection in which the left pulmonary vein connected to the portal vein and the right one was atretic as demonstrated by pulmonary artery wedge angiography. The left common pulmonary vein and right pulmonary veins were anastomosed to the left atrium, separately. The patient tolerated the operation and has been well. Early total repair after accurate diagnosis was successful for this rare combination of anomalous pulmonary venous connection.

Anastomosis, Surgical↗

Iron-saturated lactoferrin as a co-mitogenic substance for neonatal rat hepatocytes in primary culture.

We studied the effect of lactoferrin on DNA synthesis in neonatal rat hepatocytes in primary culture to determine if this agent acts as a mitogen in human milk. Thymidine incorporation into the DNA of cultured hepatocytes stimulated by lactoferrin in the presence of insulin and human epidermal growth factor was examined. Iron-saturated lactoferrin increased DNA synthesis of neonatal hepatocytes by 1.5 times and this potency was the same as that of insulin. It significantly enhanced the stimulatory effect of human epidermal growth factor plus insulin; DNA synthesis under these conditions was seven times that of control. Iron-free lactoferrin did not affect DNA synthesis, nor did the exogenous addition of ferric ions. The enhancement of DNA synthesis by iron-saturated lactoferrin was significant for neonatal hepatocytes, but not for adult hepatocytes. These results suggest that iron-saturated lactoferrin, which itself had low mitogenic activity, is a co-mitogenic substance for neonatal hepatocytes in vitro.

Animals↗