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Biomedical subjects

T Ishizaka

Publications and source records attributed to T Ishizaka.

At least 19 recordsLinked to original sources
PubMed2003

Postductal origin of the left carotid, left subclavian, and aberrant retroesophageal right innominate arteries in truncus arteriosus with interrupted aortic arch.

A neonate presented to the C.S. Mott Children's Hospital at the University of Michigan with truncus arteriosus and interrupted left aortic arch, with associated postductal origin of the left carotid, left subclavian, and aberrant retroesophageal right innominate arteries. In addition, the patient was diagnosed with DiGeorge syndrome. This unique anomaly has not been previously reported. The anatomy, pathophysiology, embryology, and successful surgical management of this anomaly are reviewed in this report.

Aortic Arch Syndromes↗
PubMed2001

Blends of aliphatic polyesters. VI. Lipase-catalyzed hydrolysis and visualized phase structure of biodegradable blends from poly(epsilon-caprolactone) and poly(L-lactide).

Phase-separated biodegradable polymer blends were prepared from poly(epsilon-caprolactone) (PCL) and poly(L-lactide) (PLLA), and Rhizopus arrhizus lipase-catalyzed hydrolysis and phase structure of the blend films were investigated. Gravimetry revealed that the lipase-catalyzed hydrolysis of PCL in PCL- and PLLA-rich phases is disturbed by the presence of PLLA. Polarimetry confirmed the occurrence of a predominant hydrolysis of PCL and subsequent removal of the hydrolyzed water-soluble PCL oligomers in the blend films. Gravimetry and gel permeation chromatography of the non-blended PLLA film indicated that R. arrhizus lipase has no catalytic effect on the hydrolysis of PLLA. The phase structure of the blend films could be visualized by selective enzymatic removal of one component and subsequent scanning electron microscopic observation.

Biocompatible Materials↗
PubMed2001

Molecular cloning of feline interferon-gamma-inducing factor (interleukin-18) and its expression in various tissues.

Interleukin-18 (IL-18) is a cytokine with potent interferon-gamma-inducing activity, and plays an important biologic role in the enhancement of the activity of natural killer cells and cytotoxic T-lymphocytes. In this study, feline IL-18 cDNA was cloned and characterized to establish a basis for the prospective cytokine therapy in small animal practice. The nucleotide sequence of feline IL-18 cDNA obtained in this study was 712bp long and contained its entire open reading frame encoding 192 amino acid residues. The predicted amino acid sequence of feline IL-18 cDNA showed 77.2, 84.8, 60.2 and 62.6% similarity with those of human, dog, rat and mouse counterparts, respectively. The feline IL-18 cDNA included a putative cleavage site of IL-1beta-converting enzyme (ICE) and IL-1 signature-like sequences identified in human and mouse IL-18 cDNAs. Expression of IL-18 mRNA was detected in various tissues including spleen, liver and cerebrum in the cat.

Amino Acid Sequence↗
PubMed2001

Molecular cloning of feline hepatocyte growth factor (HGF) cDNA.

Hepatocyte growth factor (HGF) is a pleiotropic cytokine responsible for regeneration, development and maintenance of various organs, and growth, invasion and metastasis of tumor cells. A full-length feline HGF cDNA was cloned and sequenced by RT-PCR from cat liver. Feline HGF consists of 728 amino acid and contains alpha- and beta-chains encoded in a single open reading frame. The predicted amino acid sequence of feline HGF showed 93.2, 93.3 and 93.3% homology with those of human, mouse and rat HGF, respectively. The putative proteolytic processing site, all cysteine residues, and four potential glycosylation sites are conserved in all species. Therefore, feline HGF is expected to have a similar three-dimensional structure to human, mouse and rat HGF.

Amino Acid Sequence↗
PubMed2001

Results of hyperamplification of centrosomes in naturally developing tumors of dogs.

OBJECTIVE: To evaluate results of centrosome hyperamplification in naturally developing tumors of dogs. SAMPLE POPULATION: Tumor specimens from 9 dogs with tumors (rhabdomyosarcoma, osteosarcoma, chondrosarcoma, myxosarcoma, and mammary gland tumor) and 2 canine osteosarcoma cell lines. PROCEDURE: 3 antibodies for centrosome proteins (ie, anti-gamma-tubulin, anti-BRCA1, and anti-pericentrin) were used for immunohistochemical analysis. Double immunostaining for centrosomes was used to confirm the specificity of these antibodies for centrosomes. Mutational analysis of the canine p53 gene was carried out by polymerase chain reaction-single-strand conformation polymorphism analysis, and expression of canine MDM2 protein was evaluated by use of immunohistochemical analysis, using anti-MDM2 antibody. RESULTS: Immunohistochemical analysis of dog osteosarcoma cell lines with apparent aneuploidy revealed frequent hyperamplification of centrosomes in the osteosarcoma cell lines. Similar hyperamplified centrosomes were detected in the tumor tissues from all of the 9 tumors. The frequency of cells with hyperamplified centrosomes (3 to 20/cell) in each tumor tissue ranged from 9.50 to 48.1%, whereas centrosome hyperamplification was not observed in normal lymph nodes from these dogs. In 8 of the 9 tumors, mutation of p53 gene or overexpression of MDM2, or both, was detected. CONCLUSIONS AND CLINICAL RELEVANCE: Various types of naturally developing tumors in dogs often have hyperamplification of centrosomes associated with chromosome instability. Hyperamplification of centrosomes is a novel tumor marker for use in cytologic and histologic examinations of clinical specimens obtained from dogs.

Animals↗
PubMed2001

Aberrations of the p53 tumor suppressor gene in various tumors in dogs.

OBJECTIVE: To evaluate aberrations of the p53 tumor suppressor gene in naturally developing tumors in dogs. SAMPLE POPULATION: Tumor specimens from 15 dogs with various tumors, including malignant lymphoma (7 dogs), monocytic leukemia (1), mammary gland adenoma (1), mammary gland benign mixed tumor (1), rhabdomyosarcoma (1), colon cancer (1), and osteosarcoma (3). PROCEDURE: Aberrations of the p53 gene in these tumor tissues were examined by reverse transcriptase-polymerase chain reaction and single-strand conformation polymorphism analysis, using 3 fragments that covered the entire open reading frame of the canine p53 gene, followed by nucleotide sequencing of the abnormal bands. RESULTS: Point mutations, deletions, and insertions resulting in a number of amino acid substitutions of wild-type p53 were detected in 7 of the 15 tumor specimens from dogs with malignant lymphoma, monocytic leukemia, rhabdomyosarcoma, colon cancer, and osteosarcoma. Of these 7 dogs, 2 had aberrations of the p53 gene on both alleles, whereas 5 had aberrations of the p53 gene on 1 allele and concurrently lacked the wild-type p53 transcript. Many of the aberrations of the p53 gene detected in these tumors were located in the transactivation, DNA binding, and oligomerization domains. CONCLUSIONS AND CLINICAL RELEVANCE: Various naturally developing tumors in dogs often have inactivation of the p53 tumor suppressor gene, which may be 1 of the multiple step-wise genetic changes during tumorigenesis. This study indicates that p53 gene can be a target for gene therapy for tumors in dogs.

Animals↗
PubMed1999

Use of expanded polytetrafluoroethylene sutures as artificial tendinous cords in children with congenital mitral regurgitation.

OBJECTIVE: To determine the efficacy in the intermediate term of artificial cords inserted in children with congenital mitral regurgitation. METHODS: We reconstructed the tendinous cords using expanded polytetrafluoroethylene (ePTFE) sutures in 11 children with severe mitral regurgitation. In these patients, the aortic (anterior) leaflet of the mitral valve had been markedly prolapsed, the tendinous cords being partially lacking in seven, and elongated in the remaining four. In addition, one of the papillary muscles was hypoplastic in five and absent in three. The number of artificial cords constructed varied from two to six. Conventional annuloplasty was performed in all to plicate the dilated annular attachment of the valve. Ventricular septal defect was present in four patients, and other associated malformations in another two. Age at operation ranged from 9 months to 9 years old, with a mean of 4.5 years. RESULTS: All patients survived the operation. No reoperation has been needed thus far. No complications were encountered related to the use of the prosthetic materials or anticoagulation. As judged by echocardiography, regurgitation became trivial or slight immediately after the repair. In two patients, however, regurgitation recurred within 1 year of the operation. Coaptation between the leaflets was maintained by a compensatory growth at the site of attachment of the artificial cords. Catheterization demonstrated significant improvements in the end-diastolic volume of the left ventricle. CONCLUSION: Expanded polytetrafluoroethylene sutures can be used as artificial cords when attempting to repair the malformed mitral valve in children, providing excellent results in the short- and the intermediate-term after the surgical procedure.

Child↗
PubMed1999

Ventricular outflow tracts after Kawashima intraventricular rerouting for double outlet right ventricle with subpulmonary ventricular septal defect.

OBJECTIVE: To determine whether or not the ventricular outflow tracts can be efficiently constructed in patients with double outlet right ventricle with subpulmonary ventricular septal defect by the Kawashima intraventricular rerouting in which the morphologically right ventricular outlet is divided into two, one for the systemic and the other for the pulmonary circulations. METHODS: The intraventricular rerouting procedure was carried out in nine patients with this particular malformation. Age at repair ranged from 35 days to 3 years old. The distance between the attachments of the tricuspid and the pulmonary valves was 10 mm or greater in all except one patient in whom the measured value was 3 mm. Resecting subaortic musculature appropriately, a tailored patch, either oval-shaped (in seven) or heart-shaped (in two), was placed to construct an unobstructed channel for the left ventricular outflow tract with its diameter greater than that of the anticipated normal aortic orifice at the time of repair. For an unobstructed channel to the pulmonary arteries, enlargement of the right ventricular outflow tract was carried out using a patch in six. RESULTS: All patients survived the operative procedure. On postoperative catheterization, mean pulmonary arterial pressure was 15 +/- 8 mmHg, and cardiac index was calculated as 3.3 +/- 0.6 l/min per m2. It proved that the constructed left ventricular outflow tract can become larger in the longer term. Pressure gradient across the left ventricular outflow tract was greater than 20 mmHg in two patients in the intermediate term. One of these two underwent reoperation for the obstruction 10 years after the initial repair. It was suspected that use of a heart-shaped internal conduit, which seems to result from inadequate conal resection, was one of the possible causes of such obstruction in the longer term. Pressure gradient of 47 mmHg was seen across the right ventricular outflow tract in one patient, although this patient has undergone no reoperation. Enlargement of the right ventricular outflow tract could minimize postoperative obstruction for the pulmonary pathway. CONCLUSIONS: The intraventricular rerouting remains one of the attractive surgical options for repair in this particular setting, in terms of successful construction of the ventricular outflow tracts.

Child, Preschool↗
PubMed1998

[Long-term results of aortic root replacements with pulmonary autografts (Ross procedure) in five cases].

Aortic root replacement with a pulmonary autograft (the Ross Procedure) has been successfully performed in our hospital since November, 1992. The long-term results of five of the earliest cases are reported in this paper (2-3 year follow-up). The patients' ages were two months to eighteen years old. Four of the patients suffered from aortic valve stenosis, and one suffered from aortic regurgitation. Severe left ventricular failure was recognized in three cases. However, the patients recovered from surgery smoothly and without significant aortic regurgitation and left ventricular outflow tract gradients. A serious concern exist as to whether the implanted autograft in 2 months old infant would grow. In this patient, postoperative cardiac catheterization was performed after sixty days, one year, and two years. The diameter of the anulus of the pulmonary autograft enlarged from 12 mm to 18 mm over the period of two years. Compared with the calculated aortic valvular diameter from a standardized body surface area, these diameters were equivalent to 150%-162% of the standardized size at each age. The implanted pulmonary autograft has subsequently enlarged gradually and proportionally. Its function as an aortic valve was maintained even after significant enlargement of the aortic anulus to 18 mm. We therefore conclude that the Ross procedure can be recommended because of the apparent ability the pulmonary autograft to grow over time.

Adolescent↗
PubMed1998

Artificial chordae for mitral valve reconstruction in children.

BACKGROUND: Congenital mitral regurgitation continues to present a challenge for cardiac surgeons because of the diversity of the anatomy of the congenitally malformed mitral valve. We undertook aggressive repair of the mitral valve with artificial chordae for reconstruction of the prolapsed anterior leaflet in some children. The short-term results are reported herein. METHODS: Three patients with isolated congenital mitral regurgitation underwent mitral valve repair with use of expanded polytetrafluoroethylene sutures as artificial chordae. RESULTS: There have been no late deaths and no valve-related complications. Serial follow-up echocardiographic examinations have not revealed any increase in the severity of mitral regurgitation with continuing patient growth up to 39 months after the operation. CONCLUSIONS: When combined with other conservative methods of mitral valve repair, chordal replacement with expanded polytetrafluoroethylene sutures in children undergoing mitral valve reconstruction produces good short-term results. We believe that it delays and possibly prevents the need for a mechanical prosthesis with its associated complications in this young patient population.

Cardiac Volume↗
PubMed1998

Establishment of total cavopulmonary connection without use of cardiopulmonary bypass.

OBJECTIVE: To minimize deleterious postoperative influences of cardiopulmonary bypass on the pulmonary circulation immediately after the Fontan type procedure, total cavopulmonary connection was achieved without use of cardiopulmonary bypass. METHODS: Since April 1996, 15 patients including five patients with visceral heterotaxy, in whom no intracardiac procedure was needed, have undergone this operative maneuver. Age at operation ranged from 1.2 to 44.6 years. Construction of a systemic to pulmonary shunt had been previously employed in seven patients, banding of the pulmonary trunk in two patients, and the Norwood procedure in one patient. The superior caval vein was initially anastomosed to the pulmonary arteries in bidirectional fashion under temporary bypass from the superior caval vein to the atrium. The channel for draining the inferior caval vein was subsequently constructed with the aid of temporary bypass from the inferior caval vein to the atrium, using a Goretex tube in ten patients, using a pedicled autologous pericardial roll in four patients, and directly anastomosing the pulmonary trunk to the orifice of the inferior caval vein in one patient. In patients with visceral heterotaxy and an independent hepatic venous drainage, redirection of the blood flow via the caval vein as well as the hepatic vein could be successfully achieved by placing dual temporary bypasses into these veins. RESULTS: Postoperative courses were excellent in all patients. Superior caval venous pressure was 11 +/- 2 mmHg at 12 h after the operation. No blood transfusion was needed in nine patients(60%). CONCLUSION: This alternative operative procedure is undoubtedly attractive when establishing the Fontan circulation in patients undergoing no intracardiac maneuvers.

Adolescent↗
PubMed1997

Pulmonary circulation after biventricular repair in patients with major systemic-to-pulmonary collateral arteries.

OBJECTIVE: To determine factors affecting postoperative pulmonary circulation in patients with major systemic-to-pulmonary collateral arteries. METHODS: A total of 48 patients underwent biventricular repair subsequent to unifocalization at ages in the range 1-34 years. The preparative procedures consisted of ligation of the collateral arteries in 6, plasty to the pulmonary arteries using no artificial materials in 12 and extensive reconstruction using heterologous pericardial tubes in 30. The number of the pulmonary vascular segments unifocalized was 9-18 (16 +/- 3). The amount of flow draining via residual minute systemic-to-pulmonary collaterals measured at the time of repair was 4-58% (24 +/- 16%) of the total perfusion by the cardiopulmonary bypass machine. RESULTS: This value was 40 +/- 16% in 5 patients dying in the short term after repair. The number of segments was nine or ten after unifocalization in 2 of these. Another 4 patients died in the longer term, 3 of these with CATCH 22 syndrome dying because of pulmonary hypertension. Postoperative catheterization demonstrated mean pulmonary arterial pressures in the range 8-40 (21 +/- 9) mmHg and pulmonary resistance in the range 1.7-10 (5.0 +/- 2.1) units/m2. Pulmonary resistance was correlated statistically to age at repair (r = 0.77), the number of pulmonary vascular segments (r = -0.41) and to percent collateral flow (r = 0.48). The use of a heterologous pericardial tube for unifocalization was also related probably to higher pulmonary resistance. CONCLUSION: It is essential to accomplish effective unifocalizations followed by earlier definitive repair so as to establish better pulmonary circulation.

Aorta↗
PubMed1996

Results of unifocalization for pulmonary atresia, ventricular septal defect and major aortopulmonary collateral arteries: patency of pulmonary vascular segments.

Unifocalization, a surgical technique to unifocalize the pulmonary blood supply in patients with pulmonary atresia, ventricular septal defect and major aortopulmonary collateral arteries, is a useful preparative operation to extend the indication for corrective surgery. The preoperative and postoperative pulmonary angiograms of 51 patients (aged 3 months-26 years at first unifocalization, 29 males, 22 females), who underwent a total of 96 unifocalizations from December 1985 to July 1994, were studied to assess the effectiveness of each procedure of unifocalization. The procedures of unifocalization were ligation (9), angioplasty (6), direct anastomosis (25), bridging (6), additional central pulmonary artery creation (9), central pulmonary artery creation (36) and thrombectomy (5). Altogether 125 anastomoses were made, and the patency of 101 (80.2%) anastomoses was confirmed, 24 (19.2%) were shown to be occluded. The patency rate of the anastomoses between xenograft rolls and intrapulmonary arteries was 79.5% (70/88), while that between native central pulmonary arteries and intrapulmonary arteries was 83.8% (31/37; N. S.). The patency rate of the anastomoses involving intrahilar arteries was 88.0% (44/50), while that for the group involving extrahilar arteries only was 71.9% (46/64; P < 0.05). It is concluded that 1) unifocalization with the reconstruction of central pulmonary arteries using a pericardial roll is a useful method for patients with absent or hypoplastic central pulmonary arteries, 2) it is preferable to divide the fissures of lung in anastomosing pulmonary arteries of arborization abnormalities.

Adolescent↗
PubMed1996

Spontaneous degranulation of cultured bone-marrow-derived immature mast cells from X-linked immunodeficient (Xid) mice.

IgE-mediated, antigen-dependent stimulation of immature mouse mast cells cultured in IL-3-containing media produces secretion by granule exocytosis. Similar cultured mast cells were derived from X-linked immunodeficient (Xid) mice and examined by electron microscopy. In these cultures, Xid mast cells were also immature. In contrast to cultures obtained from control mice, 10-20% of the immature mast cells of Xid origin were undergoing secretion by granule extrusion in the absence of any secretogogue. Spontaneous secretion may be related to discordered tyrosine kinase function and/or signal transduction pathways in the Xid mouse.

Animals↗
PubMed1995

Effects of T-helper 2-type cytokines, interleukin-3 (IL-3), IL-4, IL-5, and IL-6 on the survival of cultured human mast cells.

Although stem cell factor (SCF) has been identified as a critical cytokine for the development of human mast cells from their progenitors, the effects of other cytokines on human mast cells are less well understood. We examined the effects of several cytokines on the survival of human mast cells of 100% purity generated in suspension cultures of umbilical cord blood mononuclear cells in the presence of 100 ng/mL recombinant human (rh) SCF and interleukin-6 (IL-6). Mast cells suspended in conventional serum-containing medium died over a period of 2 to 6 days after the withdrawal of SCF and IL-6. The cells became pyknotic and underwent DNA fragmentation characteristic of apoptosis. The addition of SCF, IL-3, IL-4, IL-5, or IL-6 to the cultures in both serum-containing and serum-free medium prolonged their survival in a dose-dependent manner. Some other cytokines, such as IL-2, IL-9, IL-10, IL-11, tumor necrosis factor-alpha, transforming growth factor-beta 1, and nerve growth factor, had no survival-promoting effect at 100 ng/mL. Preincubation of mast cells with SCF, IL-4, IL-5, or IL-6 for 24 hours during sensitization with IgE enhanced IgE/anti-IgE antibody-induced histamine release from mast cells, whereas IL-3 showed a negligible effect. Polymerase chain reaction amplification of alpha-chains of IL-3 receptor (R), IL-4 R, IL-5 R, and IL-6 R yielded products of the correct size predicted from the sequence of each receptor. The binding assay using 125I-labeled IL-3 indicated that these mast cells bear receptors for IL-3. These findings suggest that IL-3, Il-4, IL-5, and IL-6, which are mainly produced by T-helper 2 lymphocytes, might regulate the functions of human mast cells in vivo via specific receptors in allergic reactions.

Antibodies, Anti-Idiotypic↗
PubMed1995

Ultrastructural analysis of the development of human basophils and mast cells in vitro.

The ultrastructural analysis of a variety of culture systems of human cord blood mononuclear cells (spanning a 10-year research effort) is reviewed. Human basophils, eosinophils and mast cells reliably developed from their agranular precursors that are present in human cord blood. Suspension cultures and cocultures with fibroblasts were used to examine the effects on differentiation and maturation of full (fibroblast), interleukin-2-depleted (human T cells), and murine inducer T cell culture supernatants, partially purified mouse fibroblast factor(s), recombinant human interleukins 3 and 5, and recombinant human and murine c-kit ligands (stem cell factor, mast cell growth factor). Together, these studies allowed us to define the differentiation and full maturation of the basophil and eosinophil lineages and provided evidence for the induction of a form of secretion (termed piecemeal degranulation) of the basophil and eosinophil lineages in interleukin-3- or -5-supplemented cultures. Mast cells were absent from interleukin-3- or -5-containing cultures. The development of fully mature mast cells occurred regularly in fibroblast-containing cocultures; partially mature mast cells developed in fibroblast culture supernatant-, partially purified mouse fibroblast factor(s)-, and either recombinant human or murine c-kit ligand-supplemented suspension cultures. Small numbers of basophils and eosinophils were present in the suspension cultures that received c-kit ligand in its recombinant or naturally occurring forms. Ultrastructural immunogold analyses confirmed that basophils and eosinophils contained the Charcot-Leyden crystal protein (in different subcellular locations) but that mast cells did not. In both cocultures and suspension cultures, the primary event recorded for mast cells was that of differentiation and maturation, with the ultrastructural correlates of synthetic activity and granule building prevailing. Spontaneous secretory events, recognizable by ultrastructural analysis, were not evident in either mature or partially mature mast cells developing in these cultures.

Basophils↗