Biological analysis of neuroblastoma in mass screened negative cases.
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Biomedical subjects
Publications and source records attributed to K Yabuta.
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The effects of intravenous gammaglobulin (IVGG) on changes in the peripheral blood mononuclear cell subsets during acute Kawasaki disease (KD) were studied by a random selection trial of IVGG plus Aspirin (group G) compared to Aspirin alone (group A). Group G received IVGG with 200 mg/kg per day x 5 dose. The absolute counts of peripheral blood mononuclear cell subsets were assayed by a fluorescence-activated cell sorter using monoclonal antibodies of Leu series. Before therapy, patients in each treatment group had increased counts of CD14 + macrophage/monocytes compared to healthy childhood controls (P less than 0.01). After IVGG treatment group G underwent a greater decrease in their CD14 + macrophage/monocyte counts (P less than 0.01) than group A. The changes of CD3+ T cells. Leu 7+ NK/K cells and CD19+ B cells in the peripheral blood mononuclear cell subsets with treatment in group G, were similar to those in group A. These results suggest the possibility that IVGG therapy is effective in KD by modulating macrophages/monocytes.
To evaluate the angiographic features of coronary lesions in Kawasaki disease with coronary artery calcification, cinefluoroscopy and cineangiography were retrospectively reviewed in 116 patients who had undergone coronary angiography between 1982 and 1989. Angiographic abnormalities of coronary arteries were demonstrated in 55 of the 116 patients. In 5 (9.1%) of the 55 patients, 9 with calcification were identified by cinefluoroscopy and chest x-ray. Eight of the 9 calcified lesions showed a circular or ring-shape configuration. Coronary angiography revealed a total occlusion of the right coronary artery with collateral circulation from the distal left coronary artery in 2 patients and a severe stenosis of the right coronary artery in 2 patients, in whom anticoagulant therapy had not been continued during the follow-up periods. The remaining patient in whom anticoagulant therapy had been continued had bilateral aneurysms but no significant stenosis. These results indicate that a ring-shape calcification on chest x-ray in a patient with a history of Kawasaki disease may suggest an involvement by coronary artery stenosis even when anticoagulant drugs had been given. Therefore, coronary angiography should be performed to evaluate the stenotic lesions if this type of calcification is found by routine radiographic examination.
The Japanese mass screening (MS) system for neuroblastoma at 6 months of age has resulted in the earlier diagnosis of the tumor with excellent therapeutic results. However, some problems are involved in the present MS system. We present six false-negative cases, ages ranging from 1 year 11 months to 3 years 11 months. Neuroblastoma cell taken from four of these patients were studied biologically. These patients had advanced disease (one was stage III; five were stage IV). Three of the patients have died and one is terminally ill despite undergoing surgery combined with intensive chemotherapy. Cytogenetic analysis performed in three cases showed that all the cases had diploid chromosome mode associated with 1P-, double minutes (DMs), or marker chromosomes. N-myc oncogene analysis, performed in four cases, showed amplification in two; one patient had diploid chromosomes, but the other was not examined cytogenetically. These findings were strikingly different biologically from those of cases found by MS. The majority of neuroblastomas detected by MS were found to be triploid tumors without N-myc amplification. These findings suggest that the main reason for the false-negative results in the patients we examined is that they were tumor-free or the tumors were so small in size that they were unable to produce urinary vanillylmandelic acid and or homovanillic acid levels high enough to be detected at the time of MS. Therefore, we conclude that MS at 6 months of age is too early to detect neuroblastoma with a diploid chromosome mode and/or amplified N-myc oncogene. We propose that MS at the age of 1 year 6 months would be more effective to pick up these cases, because treatment strategies depend on the different biological characteristics of tumor cells.
We analyzed the expression of Fc epsilon R2/CD23 on peripheral blood macrophages/monocytes in 12 patients with Kawasaki disease (KD) using a fluorescence-activated cell sorter. The absolute counts of CD14+ macrophages/monocytes and CD23+ macrophages/monocytes were high, and were positively correlated during the acute stage of KD. These results indicate that the increased number of macrophages/monocytes during acute KD have the Fc epsilon R2/CD23 antigen present on the surface of the cells, suggesting that peripheral blood macrophages/monocytes have been activated.
We investigated 45 patients with Kawasaki disease (KD) and report the first simultaneous determination of tumor necrosis factor (TNF), interleukin 2 receptor (IL-2R) and interferon-gamma (IFN-gamma) in the serum during acute phase. Serum levels of TNF were measured by a sandwich enzyme-linked immunosorbent assay. Serum levels of soluble IL-2R and IFN-gamma were measured by a sandwich enzyme immunoassay and radioimmunoassay, respectively. Serum levels of TNF, IL-2R, and IFN-gamma were seen to increase during the acute phase of KD. In KD patients with coronary-artery lesions (CAL), the percentage of positive cases for TNF (greater than or equal to 10 U/ml), IL-2R (greater than or equal to 1056 U/ml), and IFN-gamma (greater than or equal to 0.3 U/ml) was higher than that in patients without CAL. Our results suggest that aggressive activation of immunocompetent cells develops in KD with CAL.
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The relationship between essential fatty acid (EFA) deficiency and disturbance of prostaglandin (PG) biosynthesis was studied in children after radical operation for extrahepatic biliary atresia (EBA). In addition, to investigate the method for treatment of postoperative EFA deficiency and disturbance of PG biosynthesis, the serum fatty acid and plasma PG levels were determined before and after supplementation of an EFA-rich powder (38 g of linoleic acid per 100 g of powder) through Suruga II enterostomy. Before administration of the EFA-rich powder, linoleic acid, arachidonic acid, PGE1, and PGF2 alpha levels were significantly lower in both good bile excretion and poor bile excretion groups than in the control group. After administration, linoleic acid and PGE1 levels significantly increased in the good bile excretion group as compared with the preadministration values. These results suggest that the supplementation of EFA-rich powder is an effective treatment for linoleic acid deficiency and disturbance of PGE1 biosynthesis in postoperative EBA patients.
Measurements of IgE levels in the blood of neonates were investigated using filter paper for blood collection in mass screening of congenital metabolic disorders. Time-resolved fluoroimmunometric assay system for the measurement of filter paper blood IgE levels was also studied. In an analysis of the present results, IgE values of at least 0.015U/ml, the measurement limit, were considered as high. High IgE levels in filter paper blood were seen in 28 (7.2%) of the 389 cases. When the relation with serum IgE levels at 18 months of age was investigated in 134 of 389 subjects, high serum IgE levels were also found in about 86.7% of the subjects with high IgE levels in filter paper blood. In addition, when the relation between family history of atopic disease and presence of atopic disease in the first 18 months of age was investigated in 203 of the 389 subjects, about 90% of the subjects with a family history of atopic disease and high IgE levels in filter paper blood developed atopic disease. Since filter paper blood is routinely collected in Japan, IgE levels in this blood should be widely checked for the prediction of onset of atopic disease in infants.
We report a case of Alport syndrome. The patient, a nine-year-old boy, showed macroscopic hematuria after an upper respiratory infection seven years ago. Microscopic hematuria with proteinuria was pointed out in routine urinalysis at school. He had no apparent familial history of either progressive renal diseases or deafness. Renal biopsy was performed at the age of eight, and he was diagnosed as focal segmental glomerulonephritis (mild) by light microscopy. Slight irregular thickening of the glomerular basement membrane (GBM) was observed focally by electron microscopy. Both light microscopy and electron microscopic examinations did not indicate a hereditary nephritis. The 28-kilodalton (kDa) monomers of the non-collagenous globular domain (NC-1) of type IV collagen were absent along renal glomerular capillary walls from the patient by indirect immunofluorescence while they were normally observed in glomerular capillary walls from healthy subjects and patients with a variety of non-hereditary glomerulonephritis. It was suggested that immunofluorescence using a monoclonal antibody for the NC-1 domain of type IV collagen is useful in the precise diagnosis of the patients with Alport syndrome.
The incidence of wheezing in Kawasaki disease (KD) has been investigated retrospectively. We measured plasma immunoreactive-leukotriene C4 (i-LTC4) levels of patients with KD. Wheezing was observed in 32 (12.5%) of the 256 patients with KD. Patients who had a prior history of bronchial asthma wheezed more frequently than other patients. During the acute stage of KD, plasma i-LTC4 levels both of wheezing and nonwheezing were significantly higher than those of healthy children. During the convalescent stage, plasma i-LTC4 levels of wheezing cases were higher than those of nonwheezing cases. We speculate that LTC4 contributes to the appearance of inflammatory symptoms during the acute stage of KD. During the convalescent stage when patients were taking aspirin, the presence of wheezing was associated with increased plasma levels of i-LTC4. More attention should be paid to the appearance of wheezing during the course of KD, especially in those cases in which the patient has a prior history of bronchial asthma.
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The clinical features and outcome after various surgical procedures on 9 patients with coarctation or interruption of the aortic arch and malalignment ventricular septal defect (group 1) were compared with those of 9 patients with the arch anomaly without malalignment ventricular septal defect (group 2). Cardiomegaly and metabolic acidosis were prominent in group 1. Five of the 9 patients in group 1 died in the immediate postoperative period (56% mortality), but no operative deaths occurred among 8 patients in group 2 (p less than 0.01). The ratio of left ventricular outflow tract to ascending aortic diameter was 0.59 +/- 0.09 in group 1 and 1.03 +/- 0.11 in group 2 (p less than 0.01). Three of 4 patients with a ratio of less than 0.6 died, but no operative deaths occurred among the 6 patients who had a palliative operation and in whom the ratio was more than 0.6. These data suggest that left ventricular outflow tract obstruction is critical when the ratio of left ventricular outflow tract to ascending aortic diameter is 0.6 or less. The presence of severe left ventricular outflow tract obstruction necessitates modification of the present surgical strategy.