Experiments with rectangular supersonic jets with potential noise reduction technology.

This paper describes the aeroacoustics experiments conducted with supersonic jets, exhausting from rectangular nozzles with an aspect ratio of 2, to examine the jet noise reduction by two different methods. The first method involves the use of fluid inserts, which are produced by distributed air blowing into the diverging section of a convergent-divergent exhaust nozzle. The second method involves the integration of fluid shields in dual flow rectangular jets. In the dual flow nozzle, a single shield below the exit is augmented with fluid shields extending on both sides of the rectangular jet. The purpose of the extended bypass flow is to reduce the noise radiated to the sides of a jet aircraft. In addition to the nozzles with the two noise reduction configurations, acoustic measurements are performed with a single flow rectangular jet, referred to as the baseline. In all cases, the jets are operated as overexpanded, shock-containing jets. In some cases, the jets are operated with the core flow mixtures of helium and air to simulate high temperature jets. The far-field noise measurements are performed on an arc with the microphones approximately 70 equivalent nozzle diameters from the nozzle exit. For the purposes of assessing the noise reduction capability of the dual stream jet, comparisons are made with a baseline rectangular jet on an equal thrust per unit exit area basis. The nondimensional acoustic spectra and overall sound pressure level directivities are shown and compared.

Estimation of glycaemic control in the past month using ratio of glycated albumin to HbA1c.

AIMS: To evaluate comprehensively the use of the glycated albumin to HbA1c ratio for estimation of glycaemic control in the previous month. METHODS: A total of 306 children with Type 1 diabetes mellitus underwent ≥10 simultaneous measurements of glycated albumin and HbA1c . Correlation and concordance rates were examined between HbA1c measurements taken 1 month apart (ΔHbA1c ) and glycated albumin/HbA1c ratio fluctuations were calculated as Z-scores from the cohort value at enrolment of this study cohort (method A) or the percent difference from the individual mean over time (method B). RESULTS: Fluctuations in glycated albumin/HbA1c ratio (using both methods) were weakly but significantly correlated with ΔHbA1c , whereas concordance rates were significant for glycaemic deterioration but not for glycaemic improvement. Concordance rates were higher using method B than method A. CONCLUSIONS: The glycated albumin/HbA1c ratio was able to estimate glycaemic deterioration in the previous month, while estimation of glycaemic improvement in the preceding month was limited. Because method B provided a better estimate of recent glycaemic control than method A, the individual mean of several measurements of the glycated albumin/HbA1c ratio over time may also identify individuals with high or low haemoglobin glycation phenotypes in a given population, such as Japanese children with Type 1 diabetes, thereby allowing more effective diabetes management.

ELISA-plaque assay for the detection of platelet antibody-secreting cells. I. Studies on optimization of reagent concentrations and culture conditions for enumeration of spot-forming cells.

This report describes a modified ELISA-plaque assay that we have succeeded in developing and utilizing for the detection of platelet antibody-secreting cells (PASC). We investigated the effects of various culture conditions on the formation and specificity of plaques obtained from spleen cells and peripheral blood leukocytes (PBL) of mice immunized with human platelets. The values of PASC using this plaque assay were compared with the corresponding serum platelet-binding IgG (PBIgG) levels. The results revealed that plaque formation from spleen cells was well correlated with the number of inoculations, whereas that from PBL was not. The rise of PBIgG levels in sera was shown to be delayed, as compared with the plaque formation from spleen cells.

A cooperative clinical trial of high-dose immunoglobulin therapy in 177 cases of idiopathic thrombocytopenic purpura.

A study was conducted with the cooperation of 31 university hospitals and 44 general hospitals in Japan on high-dose immunoglobulin therapy for idiopathic thrombocytopenic purpura (ITP). Sulfonated immunoglobulins were administered to 177 patients, comprising 102 children and 75 adults for two to seven days, and a favorable rise of platelet count was found in 114 (64.4%) of these patients. In particular, of the 107 patients who had not responded favorably to adrenocortico -steroids therapy, 63 cases showed a favorable rise of platelet count. And of the 14 patients who had not responded favorably to splenectomy, 6 cases showed a favorable rise of platelet count. In the majority of cases the platelet count fell to its pretreatment level within one month after the start of sequence of administration. Although a dosage of 400 mg/kg/day was suitable for most patients, the wide range of individual responses suggested the desirability of determining an optimal dose for each patients.

Analysis of leukemic cell activity with a simple acridine orange staining method.

Leukemic cells from 28 patients with acute lymphoblastic leukemia (ALL) were supravitally stained with acridine orange (AO). Based on the staining characteristics of their cells, the patients were divided into an orange cell-dominant group (15 patients) and a green cell-dominant group (13 patients). The prognosis was better in the former than in the latter group. Orange cells which had high RNA contents were observed, while the proportion of dividing cells was high. Supravital staining with AO is a very simple and useful method for assessing the metabolic activity of leukemic cells in ALL; this method may thus be useful in assessing the prognosis of these patients.

A prospective, randomized trial of conventional, dose-accelerated corticosteroids and intravenous immunoglobulin in children with newly diagnosed idiopathic thrombocytopenic purpura.

To determine the minimal essential treatment for childhood acute idiopathic thrombocytopenic purpura (ITP), a prospective, randomized trial was conducted focusing on hemorrhagic manifestation as well as platelet count. Subjects with a platelet count of <10 x 10(3)/microL or 10 to 29 x 10(3)/microL and mucosal bleeding (group 1) were randomly assigned to receive intravenous immunoglobulin (IVIg) at 1 to 2 g/kg, conventional oral prednisolone (o-PSL) (2 mg/kg for 2 weeks). parenteral methylprednisolone (mPSL) (5 mg/kg for 5 days), or pulsed parenteral methylprednisolone (PmPSL) (30 mg/kg for 3 days). Subjects with a platelet count of 10 to 29 x 10(3)/microL without mucosal bleeding (group 2) were randomized to receive either o-PSL or no treatment. In subjects with a platelet count of 30 x 10(3)/microL or higher (group 3), patients undergoing no specific treatment were monitored. In group 1, IVIg offered faster platelet enhancement compared with o-PSL and mPSL, although neither mPSL no PmPSL showed any advantage, even over o-PSL. Platelet response was uniformly excellent when pretreatment platelet coun was > or = 10 x 10(3)/microL. Furthermore, the presence or absence of mucosal bleeding in subjects with a platelet count <10 x 10(3)/microL had no effect on the response to treatment. In group 2, platelet increase was indifferently attained with or without o-PSL. These data suggest that childhood acute ITP with a platelet count > or = 10 x 10(3)/microL may be left untreated or may be treated with o-PSL when mucosal bleeding is evident, whereas for those with a platelet count <10 x 10(3)/microL, IVIg is the most predictable platelet enhancer. Thus, a platelet count of 10 x 10(3)/microL seems to be informative enough to decide whether to treat childhood acute ITP.

Establishment and characteristics of a T-cell acute lymphoblastic leukemia cell line, JK-T1, with a chromosomal translocation between 8q24 and 14q13.

A human leukemia cell line, JK-T1, was established from the bone marrow of a 10-year-old boy with T-cell acute lymphoblastic leukemia. The origin of the leukemic cell line, JK-T1, was demonstrated by its chromosomal and immunologic similarity to the patient's fresh leukemic cells. Karyotypic analysis revealed 46,XY,del(6)(q?),t(8;14)(q24;q13),der(9)t(9;?)(q34;?). In JK-T1, neither rearrangement nor amplification of the c-myc gene was observed apparently because the breakpoint of chromosome 14 was not q11 but q13. JK-T1 was independent of interleukin 2 (IL-2) because of little production of IL-2, little IL-2 receptor (CD25) on the surface, and no response to exogenous IL-2. JK-T1 had lymphocyte function associated antigen-1 (LFA-1) (CD11a, CD18) on its surface and could adhere to the hematologic stromal layer. These characteristics of JK-T1 cell line are considered to be useful not only for evaluating the role of t(8;14) but also in studying the adhesion molecules of leukemia.

Clinical evaluation of a pasteurized factor XIII concentrate administration in Henoch-Schönlein purpura. Japanese Pediatric Group.

Arthral, abdominal and renal symptoms in Henoch-Schönlein purpura (HSP) were scored. Coagulation factor XIII (F XIII) activity was determined in fifty-six children with HSP and the correlation with the severity score of the clinical symptoms was investigated. As a result, it was found that the decrease in F XIII level was correlated with the severity score of clinical symptoms, particularly abdominal symptoms. Based on the results, a controlled study was performed in 24 cases with moderate symptoms divided into a group treated with F XIII concentrate and a non-treated group to investigate clear-cut efficacy as a next study. In three days after the administration the symptoms were improved remarkably in accordance with the increase of F XIII level compared with non-treated group and scoring of clinical symptoms was confirmed to be useful for assessing the application of the F XIII concentrate to HSP.

Establishment of a neuroblastoma cell line and induction of lymphokine-activated killer (LAK) activity against the autologous neuroblastoma cell line.

We have established a new human neuroblastoma (NB) cell line from the bone marrow of a 1-year-old boy with NB, termed JK-NB1, which showed constant growth for as long as 17 months or more, similar phenotype to those of other reported NB cell lines, colony formation in liquid and methylcellulose culture, N-myc amplification, high expression of N-CAM, and NSE production. We have tried to induce LAK cell activity with peripheral blood mononuclear cells (PBMCs) from the patient against the autochthonous JK-NB cells. PBMCs from the patient proliferated up to 20-fold in the presence of interleukin-2 (IL-2) after 9 days of incubation, and LAK activity increased up to 24.7-fold and killed all of the JK-NB1 cells. In contrast, IL-2 alone or PBMCs from the patient or a healthy adult donor had little effect on the growth of NB cells. These data suggest that it is possible to induce LAK cell activity in PBMCs from the patient against autologous as well as allogenic NB cells, and provide a rational base for the clinical use of IL-2 as one of the treatments for NB.

[Laboratory and clinical studies on T-1982 (cefbuperazone) in the field of pediatrics].

T-1982 (cefbuperazone), a new 7 alpha-methoxycephem antibiotic, was fundamentally and clinically studied, and the following results were obtained. The antibacterial activities of T-1982 against clinical isolates of S. aureus, E. coli, K. pneumoniae, S. marcescens, P. mirabilis and P. aeruginosa were determined in comparison with those of CER, CEZ, CMZ and CTT. Against S. aureus, CER and CEZ exhibited excellent activity, whereas T-1982 was less active with the peak MIC of 12.5 micrograms/ml even with the inoculum size of 10(6) cells/ml. The activity of T-1982 was equal to that of CTT and by far superior to that of CER, CEZ and CMZ against E. coli, K. pneumoniae and P. mirabilis, the peak MICs with the inoculum size of 10(6) cells/ml being less than or equal to 0.1-0.2 microgram/ml, less than or equal to 0.1-0.2 microgram/ml and 0.2-0.39 microgram/ml, respectively. Against S. marcescens, T-1982 was superior to CMZ and CTT and 48% of the strains were inhibited by 3.13 micrograms/ml or less, whereas all the strains were resistant to CER and CEZ. The MIC of T-1982 against most strains of P. aeruginosa was more than 100 micrograms/ml. 10 mg/kg or 20 mg/kg of T-1982 was administered by one shot intravenous injection or 1 hour drip infusion to 23 pediatric patients to measure serum levels and urinary recovery. At 30 minutes after one shot injection of 10 mg/kg and 20 mg/kg, the highest serum levels of 22.0-38.8 micrograms/ml and 52.4-80 micrograms/ml were observed, the half-lives being 1.32 hours and 1.76 hours. When given by 1 hour drip infusion, the serum levels attained the peaks of 29.2-42.6 micrograms/ml and 49.0-75.6 micrograms/ml at the end of infusion, the half-lives being 1.24 hours and 1.19 hours. The urinary recovery rates within 6 hours were 74.2-92.5% and 50.2-66.5% by one shot injection and 63.4-84.2% and 53.9-79.0% by drip infusion. T-1982 was administered at a dose of 50 mg/kg by 30 minutes drip infusion to a child with purulent meningitis. The levels of T-1982 in the cerebrospinal fluid at 1 hour after administration were 4.8-6.7 micrograms/ml with the CSF/serum ratios of 4.4-8.4%. A total of 36 pediatric patients (21 cases of respiratory tract infection, 9 cases of urinary tract infection and each 1 case of purulent cervical lymphadenitis, scarlet fever, purulent meningitis, acute colitis, peritonitis and sinusitis) was treated with 40-80 mg/kg/day of T-1982 (252.6 mg/kg/day in purulent meningitis). The response was excellent in 27 patients and good in 7 patients, the efficacy rate being 94.4%. Diarrhea or eruption were observed in each 1 case. No abnormal laboratory findings were noted in any cases.

[Clinical evaluation of aztreonam for infections accompanying febrile neutropenic children with hematologic disorders and solid tumors. A cooperative study].

One hundred four children with infection accompanying hematologic disorders and solid tumors were treated with aztreonam (AZT) (120-150 mg/kg), either alone or in combination with one of the following drugs; cefmetazole (CMZ) (120-150 mg/kg), piperacillin (PIPC) (120-150 mg/kg), or amikacin (AMK) (5-10 mg/kg). The overall efficacy rate was 69.2%. Efficacy rates by regimen were as follows: AZT alone was 63.2%, AZT plus CMZ was 73.6%, AZT plus PIPC was 74.1% and AZT plus AMK was 20.0%. Efficacy rates in different types of infections were 53.2% for sepsis and suspected sepsis, 78.9% for pneumonia and respiratory tract infection, 93.1% for fever of undetermined origin and 55.6% for other infections. The efficacy rate was 71.3% in 94 patients in whom causative organisms were not identified and 50.0% in 10 patients in whom causative organisms were identified. Most of infections in which causative organisms were identified were caused by Gram-negative pathogens. The response rate among infections caused by Gram-negative bacilli was 50.0%. A combination of AZT and CMZ or PIPC was effective in 3 (100.0%) out of 3 patients in whom Escherichia coli was the causative organism. Efficacies classified according to different neutrophil counts were 59.3% for less than or equal to 100/microliters, 78.6% for 101-500/microliters and 82.4% for greater than or equal to 501/microliters. No significant adverse reactions were observed. These results indicated that combination of AZT and 2nd generation cephalosporins or penicillins were well tolerated and effective for infections complicated with accompanying hematologic disorders and solid tumors.

[The measurement of erythrocyte zinc protoporphyrin/heme ratio in various anemias in childhood].

The measurement of erythrocyte zinc protoporphyrin (ZPP) with a hematofluorometer is known to be a simple and cost-effective method to screen iron deficiency and lead poisoning. We measured ZPP on blood samples from 201 children suffering from various diseases, which revealed that ZPP has better sensitivity and specificity for identifying iron deficiency than serum ferritin and percent transferrin saturation. ZPP levels in various anemias were also measured. ZPP rose markedly (> 200 mumol/mol heme) in untreated iron deficiency anemia and returned to normal in 3-4 months since the initiation of iron therapy. Moderate elevation of ZPP was observed in acute leukemia (at onset and during induction therapy), MDS, aplastic anemia and some other anemic conditions. These findings suggest that erythrocyte ferrochelatase may be unexpectedly affected in anemias even except lead poisoning.

[Detection of antigenic determinants of autoantibodies in idiopathic thrombocytopenic purpura using anti-platelet monoclonal antibodies and flow cytometry in whole blood].

To detect antigenic sites of platelet-bound autoantibodies in chronic ITP, whole blood or platelet-rich plasma from patients was stained with monoclonal antibodies (MoAbs) directed against platelet membrane glycoproteins (GPs) and with FITC-conjugated anti-mice IgG in an unwashed system followed by flow cytometric analysis. Platelets were identified by light-scattering profile and the amount of anti GP MoAb bound to platelets was measured and expressed as mean fluorescence intensity. This system enabled to quantitate the amount of intact GPs on platelet surface, regardless of activation of platelet. As a result, decreased amount of platelet-bound anti GPIIb/IIIa MoAb was noted in 5 of 22 patients with chronic ITP comparing to those with normal subjects. On the contrary, none of these patients revealed any demonstrable decrease in the amount of anti GPIb MoAb binding. From these observations, we suggest that the decreased MoAb binding to platelets in these five patients indicates the binding of autoantibody directed toward antigenic determinants, which are on or close to the epitope of this MoAb.

[Effective combination therapy by recombinant erythropoietin and cepharanthin in a girl with refractory anemia].

A 3-year-old girl was admitted with a one-month history of a tendency to bleed to Jikei Kashiwa hospital in May, 1992. She developed pancytopenia as follows; hemoglobin: 8.6 g/dl, red blood cell: 316 x 10(4)/microliters, reticulocyte: 9,480/microliters, white blood cell: 2,500/microliters (neutrophil: 400/microliters) and platelet count: 2.7 x 10(4)/microliters. Her bone marrow was hypoplastic, but was so dysplastic in 3 cell-lines as to be diagnosed as hypoplastic refractory anemia. After two courses of methylprednisolone pulse therapy followed by oral prednisolone therapy which were not effective and were supplemented by blood transfusions, the treatment of 20mg/day oral Cepharanthin, a biscoclaurine alkaloid, and intravenous recombinant human erythropoietin (rhEPO) twice a week at dose of 6,000 U/week was initiated in January, 1993. About 3 months later she showed a steady rise in hemoglobin concentration (from 4.1 to 11.9 g/dl) and platelet count (from 4,000 to 39,000/microliters). Although the rhEPO was tapered and ceased in September, 1993, her hemoglobin concentration has ranged from 11.0 to 11.9 g/dl and her platelet count from 30,000 to 40,000/microliters by giving her Cepharanthin and low dose prednisolone.

[Glutathione synthetase deficiency].

CASE REPORT: The patient was a boy born in June, 1990. The proband's father had a history of nonspherocytic hemolytic anemia. The patient was anemic at birth (Hb 11.9 g/dl) and had a hemolytic attack on postnatal day 2. His hemolysis became well compensated, and his second hemolytic episode occurred at three years of age. CLINICAL AND LABORATORY FINDINGS: The patient's mental development had so far been normal and he has no neurological symptoms. His only clinical manifestation has been compensated hemolytic anemia with a hemoglobin concentration of about 11.0 g/dl and a reticulocyte count of 3-6%. He was positive on the Heinz body formation test, and target cells were seen on his peripheral blood smear. The osmotic fragility test yielded slightly increased value. Decreased reduced glutathione (GSH) was observed (4.4 mg/dlRBC) (normal range: 63.9 +/- 9.6), and he also had decreased glutathione synthetase (GS) activity of 0.03 U/gHb (0.38 +/- 0.08 U/gHb). A diagnosis of GS deficiency was made. Decreased glutathione S-transferase (GST) activity was also found (0.57 U/gHb) (normal range: 6.65 +/- 1.20). DISCUSSION: GS deficiency has been reported in about 30 families all over the world. This patient was the first Japanese patient with red cell GS deficiency.

[Abnormalities of beta spectrin with hereditary elliptocytosis in mother and child].

It is generally considered that abnormality of the erythrocyte membrane skeleton co elliptocytes. There are, however, few reports of beta spectrin variants. We found a new variant of beta spectrin in a child and her mother. This report is the first case of abnormality of beta spectrin in Japan. The propositus was an 8 month-old girl who was first examined by us in 1988. On laboratory findings, she showed anemia, increased reticulocyte count and decreased haptoglobin concentration. Both peripheral blood smears of patient and her mother showed typical elliptocytosis and they were diagnosed as hereditary elliptocytosis. SDS-PAGE patterns of the red cell membranes of the propositus and her mother were characterized by the presence of an abnormal component migrating immediately below the spectrin chains. We confirmed that the abnormal spectrin appeared clearly at the expense of normal beta chain. The abnormal spectrin (M.W. 216,000d) makes up 16% of the total beta chain. The inheritance of our case was autosomal dominant. The present case is considered as a new spectrin variant.

[Requirements of diagnostic criteria for aplastic anemia in children].

As a general rule, diagnostic criteria of aplastic anemia in children are the same as adult criteria. However, blood counts of normal children show wide age-related variation, therefore we must establish a system of adjustment for diagnosis of aplastic anemia in children. The data of children with aplastic anemia visiting our institutes from 1966 to 1990 were evaluated for this study. RBC below 350 x 10(4)/microliters, WBC below 4,000/microliters or neutrophils below 1,500/microliters, platelets below 8 x 10(4)/microliters, reticulocytes below 4 x 10(4)/microliters and lymphocytes over 60% were seemed to satisfy the diagnostic criteria of aplastic anemia proposed by the Study Group of hemopoietic Disorders sponsored by the Ministry of Health and Welfare of Japan. Fifteen children (4.6%) did not meet these criteria and as such were diagnosed as atypical aplastic anemia. Thirteen of them were in a pre-aplastic state and developed typical aplastic anemia within 6 months to 8 years after the initial diagnosis. Clinical findings of these patients showed the decrease in number of megakaryocytes and committed stem cells in bone marrow. Three of these patients developed acute non-lymphocytic leukemia, and 2 of them were diagnosed as Fanconi's anemias.

[Platelet-derived microparticles].

The presence of platelet fragments or platelet-derived microparticles (MP) in blood is of great interest, because it could be used as a marker for increased destruction or activation of platelets followed by their aggregation and vesiculation. In addition to early electronmicroscopic observations, a variety of methods to detect MP in plasma and serum have been developed, including immunoelectrophoresis, radioimmunoassay and the immunofluorescence test using flow cytometric analysis. In these techniques, monoclonal antibodies directed against platelet membrane specific antigens, such as glycoprotein (GP) IIb/IIIa or GP I b, have been used to distinguish platelet microparticles from other components. From basic and clinical investigations, MP has proved to be increased in some physiological and pathological conditions, including blood clotting, thrombin and collagen-induced activation of platelets, mechanical trauma of platelets, and immune-mediated platelet destruction. Furthermore, it has been shown that a significant part of platelet procoagulant activity resides on these small vesicles (MP), released from the platelet plasma membrane, on activation.

[Hereditary elliptocytosis].

Recently a number of different red cell membrane skeletal abnormalities have been identified in patients with hereditary elliptocytosis (HE). In Japanese patients with HE, most of skeletal abnormality was protein 4.1 abnormalities. alpha-spectrin abnormality was found only one lineage in Japan, in spite of these abnormalities were most common abnormalities in western countries. On the contrary beta-spectrin abnormalities were found in two lineages, in spite of these abnormalities were rare abnormalities in western countries. The other abnormalities, such as band 3 abnormalities and glycophrin abnormalities, were found in HE. We described here about clinical features and above mentioned abnormalities of red cell membrane skeleton in HE.