Biomedical subjects

T Akagi

Publications and source records attributed to T Akagi.

At least 253 records · Page 14Linked to original sources

PubMed1991

A new method of gene transfer into hematopoietic progenitors using liquid culture with interleukin-3 and interleukin-6.

The technique of gene transfer into hematopoietic cells is expected to offer a new form of therapeutics. As a result of studies on a gene-delivery system using granulocyte-macrophage colony-forming units (CFU-GM), a type of hematopoietic progenitor, we have established a technique for efficient gene transfer into CFU-GM. DGL, a retrovirus vector containing the SV40 promoter and the neomycin resistance gene, was constructed and found to transfer genes effectively into murine CFU-GM, which subsequently expressed the neomycin resistance gene. After gene transfer of murine non-adherent bone marrow cells precultured in liquid culture with recombinant murine IL-3 (rmIL-3) and recombinant human IL-6 (rhIL-6) for 6 days, gene transferred CFU-GM in bone marrow cells were able to proliferate 5-10-fold and the ratio of gene transferred CFU-GM to total CFU-GM reached 70-100% from less than 1% in the liquid culture with rmIL-3, rhIL-6 and neomycin for 6 days. Using this protocol, we have been able to obtain large amounts of highly concentrated gene-transferred CFU-GM for fundamental research on CFU-GM gene-delivery systems.

Animals↗

PubMed1991

Ventricular function during supine bicycle exercise in univentricular connection with absent right atrioventricular connection.

Fourteen patients with univentricular connection, absent right connection (tricuspid valve atresia) and normally related great arteries underwent rest and supine bicycle exercise equilibrium radionuclide blood pool studies. Ejection fraction, heart rate, systemic blood pressure and oxygen saturation (ear oximetry) were measured. There were 6 male and 8 female patients. Mean age +/- standard error of the mean was 14.5 +/- 1.1 years (range 6.3 to 21.1). Eight patients (group 1) had systemic to pulmonary shunts placed as palliation 8.2 +/- 2.2 years before study and 6 patients (group II) had caval to pulmonary shunts placed 11.8 +/- 1.6 years previously. Ejection fraction at rest was 54 +/- 2% and an abnormal response to exercise (failure of ejection fraction to increase greater than or equal to 5% from rest to peak exercise) was found in 9 of 14 patients. When analyzed separately, ejection fraction at rest in group I was higher than in group II; however, this difference disappeared at peak exercise. There was a significant negative correlation between ejection fraction at peak exercise and the interval since palliative surgery, although it was not apparent at rest. These data suggest that ventricular function is compromised during exercise and that abnormal performance is influenced by long-standing volume overload. Importantly, this abnormal state is concealed at rest and the choice of palliative shunting procedure appears to have little effect on normalizing pump performance.

Adolescent↗

PubMed1991

Immunohistochemical study on the distribution of alpha and beta subunits of S-100 protein in brain tumors.

The immunohistochemical distribution of alpha and beta subunits of S-100 protein (S-100 alpha, S-100 beta, respectively) in 138 cases of human brain tumors was investigated by the avidin-biotin immunoperoxidase method. Brain tumors can be divided into four groups: group 1 [S-100 alpha (+) and/or S-100 beta (+)]; astrocytoma, glioblastoma, ependymoma, subependymoma, oligodendroglioma, choroid plexus papilloma, gangliocytoma, meningioma, chordoma, malignant melanoma. Group 2 [S-100 alpha (+) and S-100 beta (-)]; pineoblastoma, pituitary adenoma, craniopharyngioma, rhabdomyosarcoma. Group 3 [S-100 alpha (-) and S-100 beta (+)]; acoustic Schwannoma. Group 4 [S-100 alpha (-) and S-100 beta (-)]; medulloblastoma malignant lymphoma, germinoma. The S-100 beta immunoreactivity pattern in brain tumors was similar to those obtained using conventional anti-S-100 protein sera. In the first group of brain tumors both the number of positively stained tumor cells and the staining intensity were generally greater for S-100 beta than for S-100 alpha with a few exceptions including one gemistocytic astrocytoma, one subependymoma, one malignant melanoma, and some cases of glioblastomas. As to the relationship between malignancy and S-100 protein in glioma, S-100 beta immunoreactivity decreased according to degree of malignancy, while that of S-100 alpha varied, suggesting a heterogeneity of tumor cells in glioblastomas. Immunostaining for S-100 alpha and S-100 beta might become a useful diagnostic procedure in brain tumors and may give us more detailed and precise data of S-100 protein in brain tumors.

Avidin↗

PubMed1991

Salicylate treatment in Kawasaki disease: high dose or low dose?

Salicylate is the basic therapy for Kawasaki disease, however its optimal dose is controversial. We investigated the therapeutic efficacy of high dose (100 mg/kg per day, n = 30) versus low dose (30 mg/kg per day, n = 30) salicylate. Duration of fever, SGPT, serum salicylate, plasma thromboxane B2 (TxB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha) levels were compared before enrollment and on days 4, 7 and 14 of treatment. In the high dose group, duration of fever was significantly shorter than that of the low dose group (3.2 +/- 0.3 versus 5.4 +/- 0.8 days, P less than 0.05), however, SGPT levels were significantly elevated (157 +/- 34 versus 48 +/- 11 IU/1, P less than 0.05). No differences in the incidence of coronary artery lesions were observed (5/30 versus 7/30). Plasma TxB2 production was completely blocked in both groups, and plasma 6-keto-PGF1 alpha levels in the high dose group on day 14 was lower than that in the low dose group (39 +/- 8 versus 159 +/- 65 pg/ml, P less than 0.05). SGPT and plasma 6-keto-PGF1 alpha correlated with serum salicylate concentration. These data suggest that high dose salicylate therapy may be disadvantageous as anti-thrombotic therapy, and supports the notion that low dose therapy is safe in the acute stage of Kawasaki disease.

6-Ketoprostaglandin F1 alpha↗

PubMed1991

The relationship between anesthetic potency (minimum alveolar concentration) and molecular shape; structural studies on conventional inhalational anesthetics.

We have explored the ability of molecular mechanics energy calculation as a probe to obtain quantitative information about the molecular shape and energies of inhalational anesthetics. (Molecular mechanics is a readily accessible, nonquantum mechanical method of computing detailed molecular structure from energetical viewpoint.) From this aspect, the structure-activity relationships of ten inhalational anesthetics were studied. Using this method, stable conformers of these anesthetics are deduced with various physicochemical parameters. The importance of dipole interaction as the major determinant of stable conformation was suggested, and reasonable correlations between anesthetic potency (minimum alveolar concentration: MAC) and components of dipole moments, with reference to the specific sites of molecules, were obtained. The results indicate that there are important polar components which play a major role in anesthesia.

Journal Article↗

PubMed1991

Natural history of dilated cardiomyopathy in children.

To assess the natural history and potential risk factors in childhood dilated cardiomyopathy, we investigated 25 patients (ages 9.6 +/- 4.4 years) who presented after they were 2 years old. All patients had symptoms of congestive heart failure and reduced contractility with a dilated left ventricle at presentation. Two factors at presentation were significantly different between patients who died less than 1 year after the presentation (n = 14) and those who survived for more than 1 year (n = 9); cardiothoracic ratio (65.1% +/- 6.8% vs 57.1% +/- 6.1%, p less than 0.01) and left ventricular ejection fraction (31.3% +/- 7.0% vs 40.0% +/- 6.2%, p less than 0.05). Irrespective of intensive medical therapy, dilated cardiomyopathy in children had a poor prognosis; the actuarial survival rate was 41% at 1 year and 20% at 3 years. Other forms of therapy should be considered in the early stages of dilated cardiomyopathy in this high-risk group.

Cardiomyopathy, Dilated↗

PubMed1991

Intracoronary urokinase in Kawasaki disease: treatment and prevention of myocardial infarction.

The main cause of death in Kawasaki disease is myocardial infarction due to thrombotic occlusion of a coronary aneurysm. Intracoronary thrombolytic treatment was performed in 15 patients with Kawasaki disease with giant coronary aneurysms. Three patients had acute myocardial infarction, four demonstrated silent myocardial infarction, three suffered chest pain and five did not show ischemia features but had massive thrombus in the coronary aneurysms. Urokinase was infused into the coronary aneurysms as a bolus of 8,000 to 10,000 units/kg via a catheter over 10 minutes. Partial but significant coronary recanalization was achieved after injection of urokinase in a patient with acute myocardial infarction. Complete resolution of massive intracoronary thrombi was observed in 3 of 15 patents, and partial resolution was recognized in 4 cases. In 7 patients, the size of thrombus did not change. Recurrence of the thrombus was observed in 4 patients by serial two-dimensional echocardiography. Urokinase was readministered and two showed significant reduction in the thrombus. All patients have been followed for more than 2 years with longest 8 years (mean: 3.3 yrs), and none have had a recurrence of myocardial infarction or died. These findings suggest that intracoronary urokinase is useful for the treatment and prevention of myocardial infarction in Kawasaki disease.

Child↗

PubMed1991

Effect of a long-acting somatostatin analogue (SMS 201-995) on a growth hormone and thyroid stimulating hormone-producing pituitary tumor.

A 46-year-old woman with acromegaly and hyperthyroidism due to a pituitary adenoma. She had high serum thyroid-stimulating hormone (TSH) levels and very high serum growth hormone (GH) levels. Transsphenoidal removal of the tumor, post-operative irradiation, frontal craniotomy for removal of residual tumor and large-dose bromocriptine therapy were carried out consecutively. After therapy, serum GH levels gradually decreased, but not to the normal range, and serum TSH levels remained at inappropriately normal levels. Using immunoperoxidase techniques, GH-, TSH- and follicle-stimulating hormone (FSH)-containing cells were demonstrated in the adenoma. A long-acting somatostatin analogue (SMS 201-995, 600 micrograms/day) suppressed the serum GH level to the normal range with a concomitant suppression of TSH. Furthermore, the paradoxical serum GH responses to TRH and LH-RH were slightly improved. No important subjective side-effects were noted. Therefore, SMS 201-995 appeared to be a very effective drug in this patient with a GH- and TSH-producing pituitary tumor.

Acromegaly↗

PubMed1991

A monoclonal antibody (OPT1) to T cells which is available for paraffin-embedded materials.

A monoclonal antibody (MAb), OPT1, reactive with T cells in formalin-fixed, paraffin-embedded tissue sections, has been identified through immunization with activated T cells from peripheral blood lymphocytes (PBL). The antibody is an IgG1 antibody as demonstrated by the Ouchterlony technique. By cytofluorometric analysis, almost all CD3+ lymphocytes and only a few CD20+ lymphocytes of peripheral blood expressed the OPT1 antigen. Nonhematolymphoid cell lines were negative for OPT1 by the immunoperoxidase staining using acetone-fixed cell lines. On the contrary, peripheral T cells, cells of two T cell lines out of four and a part of the cells of one B cell line out of two were positive for OPT1. The immunoperoxidase staining of paraffin-embedded tissue sections revealed that most of lymphocytes in T cell areas of lymph nodes expressed OPT1 antigen. Some lymphocytes in both cortex and medulla of the thymus and erythroid precursors of the bone marrow were OPT1+. In the malignant lymphoma series, approximately 90% of T cell lymphomas and 6% of B cell lymphomas reacted with OPT1. None of the Reed-Sternberg cells nor Hodgkin cells in Hodgkin's disease were positive. Consequently, OPT1 may be useful for the diagnosis and study of malignant lymphomas and other related lesions.

Antibodies, Monoclonal↗

PubMed1991

Pre-elastofibroma-like colonic polyp: another cause of colonic polyp.

We present a case of pre-elastofibroma-like lesion, a kind of elastic-producing fibrous tumor. The small colonic polyp, which was found in a 49-year-old asymptomatic man in association with a large colonic adenoma, showed submucosal nodular deposits of fine granular or fibrillar eosinophilic materials with interspersed fibroblastic cells. Elastic stain revealed these deposits to consist mainly of dark gray granular or partially fibrillar dense elastinophilic materials, most of which were digested with elastase. This stromal lesion somewhat resembled a pre-elastofibroma. Therefore, pre-elastofibroma-like lesions should be kept in mind as a possible origin of colonic polyp.

Colonic Polyps↗

PubMed1991

[Cine magnetic resonance imaging for evaluating flow dynamics in congenital heart diseases with left-to-right shunts].

Cine magnetic resonance imaging (cine MRI) was used to evaluate the cardiac structures and blood flow in congenital heart diseases with left-to-right shunts. Fifteen children with left-to-right shunts which were confirmed by echocardiography or angiography were investigated in the present study. Five children each had atrial septal defect, ventricular septal defect, and complete endocardial cushion defect. Their ages ranged from 4 months to 13 years (mean 5.5 years). Prior to cine MRI, the ECG-gated cardiac imaging using multi-slice acquisition was performed in all the children to localize the optimal slice for cine MRI. To select the optimal imaging planes for various cardiac structures, we used axial, coronal, sagittal and four-chamber views. Cine MRI was demonstrated by a fast low 30 degree flip angle imaging technique, with a 15 msec echo time, a 30-40 msec pulse repetition time, and a 256 x 256 or 128 x 128 acquisition matrix. Abnormalities of cardiac structures were defined extremely well in all the children using ECG-gated cardiac imaging. In 14 of the 15 children (93%), cine MRI clearly detected a left-to-right shunt flow, which was visualized as a low signal intensity area compared to the surrounding blood flow. Noninvasively, cine MRI provides accurate images of the anatomy of the cardiac structures, makes functional assessments of the cardiac chambers and walls, and flow relationships. It has no limitations of imaging planes imposed bones and lung, and is not associated with technical difficulties as required with echocardiography which has small cardiac window.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

[Percutaneous balloon valvuloplasty for congenital aortic valve stenosis].

We performed percutaneous balloon aortic valvuloplasty for 10 patients with congenital aortic valve stenosis aged from 2 to 17 years and a 54-day-old infant with critical stenosis. The retrograde single balloon technique was used for 6 patients including the infant; the retrograde double balloon technique was used for 3 patients; and both techniques for 2 patients. The valvuloplasty was effective for 10 patients except for the infant in terms of the peak systolic pressure gradient between the left ventricle and aorta (from 80.6 +/- 21.9 to 29.4 +/- 17.0 mmHg). Follow-up cardiac catheterizations one year after valvuloplasty in 3 patients and 3 years after valvuloplasty in one patient disclosed no re-stenosis. Aortic regurgitation newly developed in one patient and advanced Sellers' classification I in 3 patients, however, all of them were asymptomatic and did not progress further. In the infant with critical stenosis, sufficient dilatation could not be achieved and acute myocardial infarction mainly at the lateral wall of the left ventricle developed during the valvuloplasty. He died 3 days after the valvuloplasty. The double balloon technique was found to be superior to the single balloon technique with the latter being ineffective in 2 cases, because the fixation of the balloon at the annulus was very difficult. Double balloon technique has low risk of vascular trauma and is applicable to a large sized annulus, because it enables blood supply between the 2 balloons during the inflation period.

Adolescent↗

PubMed1991

[A case of lacrimal gland malignant lymphoma, associated with Sjögren's syndrome].

A 64 year-old female complained of left upper lid swelling. Painless mass lesions were found in her bilateral lacrimal gland areas. She also complained of a dry sensation in both eyes and her mouth. The rose bengal test, Schirmer's test and fluorescein dye test were positive. Lip biopsy revealed chronic sialoadenitis and rheumatoid factor titer was elevated. Anti-nuclear and anti-RNP antibodies were positive. Anti-SS-A and anti-SS-B antibodies were both negative. Left pre-and post auricular, cervical and inguinal lymph nodes were palpable. Excisional biopsies of bilateral orbital lesions and an inguinal lymph node revealed the presence of reactive lymphoid hyperplasia in the right orbit, and B cell type, diffuse, large cell lymphoma, in the left orbit and inguinal lymph node. Intensive chemotherapy resulted in complete remission. Lacrimal gland lymphoma must be considered when examining cases of Sjogren's syndrome.

Eye Neoplasms↗

PubMed1991

[An autopsy case of adult respiratory distress syndrome (ARDS) with peculiar histopathological features modified by a positive end-expiratory pressure (PEEP) therapy].

A case is reported of adult respiratory distress syndrome(ARDS) combined with barotrauma due to positive end-expiratory pressure (PEEP) therapy. The patient was a 32-year-old woman with fulminant hepatitis, type B, who died of ARDS 22 days after the onset of the illness. The autopsy revealed extraordinary heavy lungs (left: 923g, right: 985g) with edema in the peripheral part and marked emphysematous changes in the central part near the hili. Histologically, scattered foci of intra-alveolar organization and interstitial fibrosis with hemorrhage were observed, which might have been the result of the proceeding pneumonia. The emphysematous lesion seen in this case was peculiar and not like any type of of ordinary pulmonary emphysema. Judging from the strange, sharply demarcated emphysematous lesion with marked destruction of alveolar structure, and the good preservation of the alveolar structure in the edematous lesion, the emphysematous lesion might be barotrauma which was induced by PEEP therapy on top of pneumonia.

Adult↗

PubMed1991

[A case of ovarian cancer with liver metastasis successfully treated by PAC therapy].

Surgery was attempted in a case of stage IV ovarian cancer with a hepatic metastatic lesion measuring 119 x 96 mm. However, radical surgery was impossible and the operation ended up as no more than exploratory laparotomy. Before closing, Cisplatin 100 mg and Etoposide 200 mg were instilled into the intraperitoneal cavity. Two courses of systemic chemotherapy with PAC (Cisplatin 50 mg, Pirarubicin 40 mg, Cyclophosphamide 400 mg) were instituted. To examine shrinkage of the hepatic metastasis and the peritoneal tumors, A "Second look" operation was conducted. Abdominal simple total hysterectomy, bilateral salpingo-oophorectomy, omentectomy and partial sigmoidectomy resulted in no residual lesions in the peritoneal cavity with the exception of the hepatic metastatic lesion (69 x 57 mm). Two additional courses of PAC therapy were administered after the "Second look" operation. The hepatic metastatic lesion shrank to 45 x 41 mm; a decrease of 83.8% compared to the pre-therapy in size. Liver function tests and tumor chemical markers (TPA, CA 125, SLX) revealed decreased values that were consistent with a tumor size reduction. Good PR was achieved with only a systemic chemotherapy; i.e., without resorting to local injections of chemotherapeutic agents into the liver.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Natural killer (NK) activity of cultured S100 beta-positive T-leukemia cells.

In order to clarify the function of human S100 beta-positive T-cells, S100 beta-positive T-leukemia cells (S100 beta TLC) were examined in vitro. S100 beta TLC were obtained from the peripheral blood of a patient with S100 beta-positive T-cell leukemia and enriched by an E-rosetting method. Two dimensional flow cytometric analysis indicated that the vast majority of the E-positive fraction were S100 beta TLC expressing CD3 and CD8 antigens. Although S100 beta TLC expressed CD3 antigen, they were negative for the alpha/beta and gamma/delta T-cell antigen receptor (TCR) defined by monoclonal antibodies (mabs) WT-31 and delta TCS-1, respectively. It was speculated that S100 beta TLC initially expressed alpha/beta TCR but lost it during malignant transformation. When S100 beta TLC were cultured for 24 h, they acquired cytotoxic activity towards various NK-sensitive cell lines including K-562, Molt-3 and CEM-CCLF, but did not exhibit lysing activity towards NK-resistant cell lines including Raji, Daudi and MT-1. Despite the NK-activity of cultured S100 beta TLC, they lacked the morphological features of large granular lymphocytes (LGL). S100 beta TLC did not exhibit lymphokine-activated killer (LAK) activity. When S100 beta TLC were cocultivated with NK-sensitive cells or NK-resistant cells, they selectively bound to NK-sensitive cells, indicating that they lysed target cells by cell-to-cell contact. The finding that S100 beta TLC lacked TCR molecules and their NK activity was not inhibited by mabs reactive with the CD3-TCR complex indicated that the CD3-TCR complex was not involved in their target recognition.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium-Binding Proteins↗

PubMed1990

Valvular heart disease in Kawasaki syndrome: incidence and natural history.

To elucidate the incidence and natural history of valvular heart disease in Kawasaki syndrome, we analyzed patients who were found to have a new heart murmur after the onset of the disease. Among 1215 patients we found 13 (1.1%) with valvular disease (12 with mitral regurgitation and one with aortic regurgitation). We compared these patients with 30 who did not have valvular lesions. The duration of fever was longer and the incidence of coronary artery lesions significantly higher than in those without valvular disease. Heart murmurs disappeared within 2 months after the onset of valvular heart disease in five patients, whereas in another six, all involving valve prolapse, they persisted for 2 years or more. We postulate that two different mechanisms may be responsible for the variation in the duration of valvular heart disease: one, which disappeared spontaneously, was attributed to pancarditis; the other, which persisted, was due to dysfunction in valve and papillary muscles as a result of ischemia.

Angiography↗

PubMed1990

Mutational specificity of the carcinogen 3-amino-1-methyl-5H-pyrido[4,3-b]-indole in mammalian cells.

We have used the pZipHprtNeo shuttle vector to determine the types of DNA sequence alterations induced by a potent carcinogen 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P2). The shuttle vector contains a human cDNA hprt as the target gene and is stably integrated into a chromosome of the mouse cell line VH12. After Trp-P2 treatment, 59 independent HPRT- mutant clones of VH12 were isolated and altered sequences of the mutant hprt- cDNA genes were determined. Mutations induced by Trp-P2 comprised a variety of events; base substitutions, frameshifts, deletions and complex. Frameshifts were the most frequent mutational events (51%), and base substitutions were the next most frequent (30%) followed by deletions (14%). Examination of the DNA sequence context in the mutant genes revealed that approximately 70% of mutations induced by Trp-P2 occurred at G:C sites and thymine residues were the suggested target for the remainder of mutations. The results seem consistent with the previously reported finding that in vivo, metabolically activated Trp-P2 specifically binds to the C8 position of guanine residues in DNA to form C8G-Trp-P2 adducts (Hashimoto et al., Mutat, Res., 105, 9-13, 1982). As for molecular mechanisms, we showed that slippage and slippage misalignment could predict the generation of a large portion of Trp-P2-induced mutations found in the cDNA gene.

Animals↗