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Biomedical subjects

K Hashino

Publications and source records attributed to K Hashino.

54 records · Page 3Linked to original sources

Evaluation of pulmonary artery histopathologic findings in congenital heart disease: an in vitro study using intravascular ultrasound imaging.

OBJECTIVES: This study aimed to 1) compare in vitro intravascular ultrasound images of human pulmonary arteries with corresponding histologic sections, and 2) correlate the relation between intravascular ultrasound findings and Heath-Edwards pathologic grade of pulmonary vascular changes. BACKGROUND: The pathologic assessment of the pulmonary vascular bed is essential for diagnosis and management of congenital heart disease with pulmonary hypertension. METHODS: We evaluated and compared intravascular ultrasound images with histologic findings at identical sites in 40 pulmonary artery segments from 17 autopsy studies: group 1 = 7 patients with pulmonary hypertension (Heath-Edwards grade I to V, 20 segments); group 2 = 10 patients without cardiopulmonary disease (20 segments). RESULTS: In group 2, the pulmonary artery wall echo consisted of a single layer. In group 1, 1) all segments of pulmonary arteries from patients with pulmonary hypertension showed a three-layered appearance; 2) in patients with mild pulmonary hypertension (Heath-Edwards grades I and II), intravascular ultrasound demonstrated increased thickness of the echoluscent zone due to medial hypertrophy with no intimal reaction; 3) patients with severe pulmonary hypertension (Health-Edwards grade III or higher) had intravascular ultrasound findings of increased medial thickness and a bright inner layer from intimal hyperplasia; 4) percent wall thickness derived from intravascular ultrasound showed a significant correlation with that determined by histologic examination (r = 0.89, p = 0.0001, n = 20). CONCLUSIONS: Changes observed with intravascular ultrasound imaging correlate well with histopathologic grade. Thus, intravascular ultrasound may have significant utility in the evaluation of pulmonary vascular morphology in patients with pulmonary hypertension.

Adolescent↗

Clinical features of childhood-onset schizophrenia with obsessive-compulsive symptoms during the prodromal phase.

Thirty-nine patients with schizophrenia, diagnosed according to DSM-III-R, who were under 15 years of age, were studied in two groups; 16 subjects with obsessive-compulsive symptoms during the prodromal phase, and 23 with no obsessive-compulsive disorders. The group with obsessive-compulsive symptoms during the prodromal phase was characterized by a higher ratio of males, higher incidences of perinatal and brain computed tomography (CT) abnormalities, fewer hereditary factors, longer duration of the prodromal phase, and a higher incidence of insidious onset and negative symptoms compared with the group without such prodromal symptoms. Schizophrenic patients with obsessive-compulsive symptoms during the prodromal phase were clinically distinct from those without, which suggests the possibility of subtype categorization.

Adolescent↗

Kawasaki disease.

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Coronary Aneurysm↗

Expression of recombinant mouse/human chimeric antibody specific to human GMP-140/P-selectin.

To construct a mouse/human chimeric antibody, we cloned the genomic DNAs for Ig from a murine hybridoma that produces PL7-6 monoclonal antibody specific to human P-selectin and expressed them in SP2/0 myelomas using a series of pSV2 vectors. Transfected cells that produce the mouse/human chimeric anti-human P-selectin antibody were geneticin-selected and screened by an immunoassay using immobilized antigen. The chimeric antibody, cPL-2R1, expressed by the resultant clone has the murine Ig variable region and the human Ig constant region. The native antibody PL7-6 and the chimeric antibody cPL-2R1 react equally with purified P-selectin and thrombin-stimulated platelets. Competitive inhibition tests demonstrated that the native antibody PL7-6 and the chimeric antibody cPL-2R1 had identical affinity for purified human P-selectin. Thus, although human IgG1 constant region was substituted for the murine counterpart in this chimeric antibody, its specificity and binding affinity for P-selectin was not altered. This chimeric antibody may prove useful when employed in combination with imaging reagents or therapeutic drugs for targeting activated platelets or endothelium in patients with thrombosis or intravascular inflammation.

Amino Acid Sequence↗

Improved method for expression of Kunitz-type serine proteinase inhibitor domain of beta-amyloid protein precursor in Escherichia coli and characterization of disulfide bonds of the product.

Kunitz-type serine proteinase inhibitor (KPI) domain of Alzheimer's disease-related beta-amyloid protein precursor (APP) was expressed in Escherichia coli as a fusion protein with a truncated form of Staphylococcus protein A. The fusion protein was purified from the cell culture medium using an IgG Sepharose column. The KPI domain was separated from the protein A portion by cleavage with human alpha-thrombin at the engineered recognition sequence, followed by purification on IgG Sepharose and reversed-phase HPLC columns. The recombinant KPI domain strongly inhibited trypsin; the inhibition constant (Ki) for bovine trypsin was 2.5 x 10(-11) M, comparable to those of the secreted forms of APP with the KPI domain. The recombinant protein contained three intramolecular disulfide bonds, which were determined to be located between Cys-6 (C1) and Cys-56 (C6), Cys-15 (C2) and Cys-39 (C4), and Cys-31 (C3) and Cys-52 (C5) of the recombinant KPI domain, respectively. These positions are highly homologous to those of disulfide bonds in bovine pancreatic trypsin inhibitor. The trypsin-inhibitory activity of the recombinant protein was abolished by preincubation with 0.4 mM dithiothreitol under non-denaturing conditions. By this mild reduction, all the disulfide bonds were completely cleaved. These results clearly indicate that the disulfide bonds play an important role in the function of the KPI domain of APP.

Alzheimer Disease↗

Engineering of artificial cell adhesion proteins by grafting the Arg-Gly-Asp cell adhesive signal to a calpastatin segment.

A new artificial cell adhesive protein was engineered by grafting the Arg-Gly-Asp (RGD) sequence, the minimal recognition signal of fibronectin for interaction with integrins, to a calpastatin segment by in vitro mutagenesis. The mutagenized protein showed cell adhesive activity in addition to calpain inhibitory activity. The RGD signal grafted to the calpastatin segment was recognized by the vitronectin receptor but not by the fibronectin receptor.

Amino Acid Sequence↗

Bulimia nervosa in a pair of male monozygotic twins.

This is a report of a pair of male monozygotic twins meeting the DSM-III-R criteria for bulimia nervosa. At the age of 15, both brothers began to diet and suffered from bulimia. They were admitted to psychiatric hospitals and separated. After admission, their clinical course dramatically changed. The differences in their clinical courses and endocrinological data are suggestive as to the roles of environmental and hereditary factors in the etiology of bulimia nervosa.

Adolescent↗

Role of type III homology repeats in cell adhesive function within the cell-binding domain of fibronectin.

Recombinant fibronectin (FN) fragments and their mutant proteins were produced to elucidate the role of type III homology repeats in cell adhesive activity within the cell-binding domain of FN. Cell adhesive activity of the 11.5-kDa fragment, the cell attachment site of the cell-binding domain, was less than 0.1% that of native FN despite the presence of the Arg-Gly-Asp-Ser sequence. The activity increased as type III homology repeats were added to the N terminus of the 11.5-kDa fragment, and a 52-kDa fragment with four additional type III repeats had almost the same activity of native FN. Deletion of Arg-Gly-Asp from the fully active fragments completely abolished the cell adhesive activity. Deletion of one or two repeats from the 52-kDa fragment affected the extent of the cell adhesive activity, the degree of the effect being inversely correlated with the distance of the deletion from the type III repeat containing Arg-Gly-Asp-Ser. Rearrangement of type III repeats caused much loss of activity. These results suggest that the number and kinds of type III repeats and their correct alignment rather than the putative synergistic site decide the extent of the specific cell adhesive activity.

Amino Acid Sequence↗

Production and characterization of functional domains of human fibronectin expressed in Escherichia coli.

An efficient expression system was constructed in Escherichia coli that produced a 33-kDa fragment, C-274, of human fibronectin with a strong cell-adhesive activity. The entire sequence of the heparin-binding domain with 271 amino acids, H-271, was also expressed. Deletion analysis of the type III repeats showed that the heparin-binding site was at type III-13. The cell-adhesive activity of a fusion protein, CH-271, containing the cell- and the heparin-binding domains was twice that of C-274 when BHK but not B16-F10 melanoma cells were tested; H-271 alone was inactive. Recombinant proteins containing the CS1 sequence of the IIICS region were more active than C-274 and CH-271 with B16-F10. However, H-296, which contained both H-271 and CS1, was almost inactive with BHK. CH-296, which contained CS1 at the C-terminus of CH-271, was more active with B16-F10 than H-296 and C-CS1, which was produced by the deletion of H-271 from CH-296. Thus, the cell-binding domain was active with both kinds of cells. The heparin-binding domain promoted the adhesion of both kinds of cells only when linked to the cell-binding domain or CS1. CS1 was specific for the adhesion of B16-F10 but was not essential.

Animals↗

Artificial cell adhesive proteins engineered by grafting the Arg-Gly-Asp cell recognition signal: factors modulating the cell adhesive activity of the grafted signal.

An artificial cell adhesive protein could be engineered by grafting the RGDS tetrapeptide, the core sequence of the major cell adhesive site of fibronectin, to a truncated form of Staphylococcal protein A (tSPA) via cassette mutagenesis of the tSPA expression vector pRIT2T [T. Maeda et al. (1989) J. Biol. Chem. 264, 15165-15168]. We synthesized a panel of tSPA derivatives grafted with various RGDS-containing oligopeptides to address the problem of how the cell adhesive activity of the resulting tSPA derivatives was affected by the length and amino acid sequence of the grafted oligopeptides and by the sites on tSPA where the extra oligopeptides were inserted. The results showed that (i) the amino acid residues flanking the RGDS core sequence played a key role in modulating the cell adhesive activity of the grafted RGDS signal; (ii) at least two sites on tSPA, each corresponding to on e of the two HindIII sites of pRIT2T, were competent in sustaining the cell adhesive activity of the grafted signal; and (iii) the divalent tSPA containing the RGDS signal at both sites was more active than monovalent derivatives containing only one signal at either site. These results provide a strategic basis for engineering of artificial cell adhesive proteins by grafting the RGDS signal.

Amino Acid Sequence↗

Partial trisomy 22 with Dandy-Walker malformation.

Partial trisomy 22 usually occurs through a 3:1 meiotic segregation of the parental 11q;22q translocation carrier, which is the most common balanced translocation in man. Common neurologic findings are delayed psychomotor development and muscular hypotonia. There have been a few neuroradiologic and neuropathologic studies, which include ventricular dilatation, arrhinencephaly, and aplasia or hypoplasia of the cerebellar vermis, corpus callosum and pons. We here add one patient with partial trisomy 22 who had, in addition to the usual features, Dandy-Walker malformation, which, to our knowledge, is a previously undescribed feature.

Chromosomes, Human, Pair 11↗

The complete amino acid sequence of rice bran trypsin inhibitor.

The complete amino acid sequence of a double-headed trypsin inhibitor (RBTI) from rice bran was determined by a combination of limited proteolysis of the native inhibitor with Streptomyces griseus trypsin at pH 3 and conventional methods. RBTI consists of 133 amino acid residues including 18 half-cystine residues which are involved in 9 disulfide bridges in the molecule. The limited proteolysis at pH 3 produced a major split of Lys(83)-Met(84) and a minor split of Arg(107)-Val(108) together with a non-enzymatic hydrolysis of Asp(19)-Pro(20) in the molecule. The established sequence showed that RBTI is composed of 4 domains, domains I and III, and domains II and IV being homologous to the first and the second domains of soybean Bowman-Birk inhibitor, respectively, indicating that RBTI has a duplicated structure of the Bowman-Birk type inhibitor.

Amino Acid Sequence↗

Noninvasive evaluation of systolic pressures of pulmonary artery and right ventricle using contrast-enhanced doppler echocardiography: comparative study using sonicated albumin or glucose solution.

Evaluation of pulmonary arterial pressure is essential for the diagnosis and management of patients with congenital heart disease; it is usually done by cardiac catheterization. An alternative, noninvasive method may be clinically more useful. The purpose of this study was to assess the usefulness of the noninvasive determination of systolic pressure of the pulmonary artery and right ventricle by contrast-enhanced Doppler echocardiography. We selected 30 pediatric patients (28 with trivial or nonsignificant tricuspid regurgitant Doppler signals and 2 with significant tricuspid regurgitant Doppler signals) aged 2 months to 21 years. The flow velocity of tricuspid regurgitation was measured with continuous-wave Doppler of the right ventricular inflow view or left parasternal or apical four-chamber view before and after injection of two types of contrast medium (hand-agitated 5% glucose or sonicated albumin). The systolic pressure of the pulmonary artery was assessed as the estimated right ventricular systolic pressure (albumin method) minus the peak pressure gradient across the pulmonary valve (nonenhanced Doppler method). After injection of hand-agitated 5% glucose and sonicated albumin, trivial tricuspid regurgitation signals were enhanced in 25 of 28 patients (89%). In two patients, spectral envelopes were well defined enough to obtain the peak systolic velocity of the tricuspid regurgitation jet without contrast medium injection. Peak velocity was not altered by injection of contrast medium in these patients. There was significant correlation between the estimation by contrast-enhanced Doppler using hand-agitated 5% glucose and the cardiac catheterization measurement of the transtricuspid pressure gradient (r = 0.88). The transtricuspid pressure gradients obtained by continuous-wave Doppler during sonicated albumin enhancement corresponded closely to those measured by cardiac catheterization (r = 0.95). Pulmonary arterial and right ventricular systolic pressures measured by Doppler using sonicated albumin and those obtained by cardiac catheterization were highly correlated (right ventricle, r = 0.96; pulmonary artery, r = 0.95). In conclusion, this technique may be a valuable noninvasive method for determining accurate right ventricular and pulmonary arterial systolic pressures.

Adolescent↗

Quantitation of the global right ventricular function in children with normal heart and congenital heart disease: a right ventricular myocardial performance index.

Although the assessment of right ventricular (RV) function is important in the clinical management of children with congenital heart disease, available imaging techniques have been limited because of the complex geometry of the right ventricle. A new Doppler index combining systolic and diastolic time intervals (the Tei index) has been reported to be useful for the assessment of global RV function in adults. However, normal values in children, age-related changes, and the clinical utility of the Tei index with regard to congenital heart disease have not been demonstrated. The purpose of this study was to prospectively assess RV function in children with normal heart and congenital heart disease using the Tei index. The subjects included 150 healthy children and 43 patients with congenital heart disease (35 patients with atrial septal defects and 8 patients who had had a Senning operation). The index was defined as the sum of isovolumetric contraction time and isovolumetric relaxation time divided by ejection time and was measured from conventional RV outflow and inflow Doppler velocity profiles. The Tei index was not affected by age in healthy children (0.24 +/- 0.04). There was a significant difference in index rating between patients who had had a Senning operation (0.58 +/- 0.09) and healthy children (p < 0.01), but there was no significant difference between children with atrial septal defect (0.25 +/- 0.13) and healthy children. The Tei index is a feasible approach to use when assessing global RV function in children with congenital heart disease.

Adolescent↗

Balloon dilatation of the pulmonary valve in a patient with pulmonary atresia and intact ventricular septum using a commercially available radiofrequency catheter.

Using a commercially available 5F deflectable radiofrequency catheter, we have succeeded in percutaneous valvotomy of an imperforate pulmonary valve and consecutive balloon dilatation in a baby with pulmonary atresia and intact ventricular septum. After the procedure, right ventricular systolic pressure fell from 125 mmHg to 65 mmHg, and right ventriculography demonstrated anterograde blood flow into the pulmonary arteries. There were no major complications. Doppler echocardiography at 1 year after the procedure demonstrated a pressure gradient across the pulmonary valve of 20 mmHg with mild pulmonary and tricuspid regurgitations.

Catheter Ablation↗

Successful embolization of coronary arteriovenous fistula using an interlocking detachable coil.

Although the efficacy and feasibility of coil embolization of coronary arteriovenous fistulas have been reported, the procedure may be complicated by migration of the coil into peripheral vessels or pulmonary arteries. We report two cases of successful coil embolization of such lesions using an interlocking detachable coil. This system can provide safer and more effective coil embolization in patients with coronary arteriovenous fistula.

Arteriovenous Fistula↗

Carotid artery approach to balloon aortic valvuloplasty in infants with critical aortic valve stenosis.

We compare the clinical efficacy of two approaches for balloon aortic valvuloplasty (BAV) in infants with critical aortic valve stenosis. The approaches were through the carotid artery and the femoral artery. Eight catheterizations for BAV were performed in seven consecutive patients with critical aortic stenosis: four BAVs were approached through the femoral artery and four through the right common carotid artery. We inserted a 5F sheath into the right common carotid artery by a cutdown procedure; after BAV the sheath was removed and the carotid arteriotomy sutured with 7-0 monofilament. Two cases in which the femoral artery approach was used resulted in failure to perform BAV; two cases had complications. All four cases with the carotid artery approach were successful, with no complications; aortography performed 3 months after one balloon valvuloplasty revealed a smooth, unobstructed right carotid artery. Use of the carotid artery approach may reduce serious complications with BAV and offers quicker, easier maneuvering in infants and neonates with critical aortic valve stenosis.

Aortic Valve Stenosis↗