Simple indicators for determining the timing of efficient collection of autologous peripheral blood stem cells in children with malignancies.
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Antigens, CD34↗
Biomedical subjects
K Iinuma
Publications and source records attributed to K Iinuma.
Growth of two children after six months interruption of GH therapy.
We describe two short boys with normal GH responses to the stimuli in whom GH therapy was interrupted for 6 months. Their growth rates before and after the interruption, and after re-administration of GH were evaluated. Height velocity (HV) in case 1 before and after the interruption was 6.6 cm/y and 5.0 cm/y, respectively. HV was not increased (5.0 cm/y) by re-initiation of GH therapy despite the high serum IGF-1 level. Height velocity (HV) in case 2 before and after the interruption was 5.6 cm/y and 3.6 cm/y, respectively. HV was slightly increased to 4.1 cm/y by re-administration of GH, but it was far below the pretreatment value. Serum IGF-1 was increased by GH in this case as well. We conclude that re-acceleration of growth by re-administration of GH after interruption of therapy, as seen in classical GHD patients, may not be expected in normal short children.
Body Height↗
Long-term follow-up study of serum immunoglobulin G and immunoglobulin A antibodies after Helicobacter pylori eradication.
OBJECTIVE: There have been few studies concerning serum titers of anti-Helicobacter pylori immunoglobulin G (IgG) antibody >12 months after eradication of the original infection. Moreover, clinical usefulness of immunoglobulin A (IgA) antibody levels remains to be established. The purpose of this study was to investigate long-term responses of serum IgG-specific and IgA-specific antibodies to H pylori in children after eradication therapy. STUDY DESIGN: A total of 34 children, 2 to 17 years of age (mean: 11.7 years) with H pylori-associated gastroduodenal disease received eradication therapy (proton pump inhibitor-based dual or triple regimens). Diagnoses included nodular gastritis (n = 8), gastric ulcer (n = 7), and duodenal ulcer (n = 19). Upper gastrointestinal endoscopy and biopsy were performed before the therapy and at 1 to 2 months' posttreatment. H pylori infection and eradication were defined by biopsy-based tests; eradication was successful in 28 patients and unsuccessful in 6. Pretreatment IgG was positive in 30 patients (88. 2%), and the IgA was positive in 31 (91.2%), who were entered into this study (duration </=24 months). Serum samples were obtained before treatment and at 1, 3, 6, 12, 18, and 24 months' posttreatment. IgG and IgA antibodies were measured using commercial enzyme immunoassay kits (HM-CAP and PP-CAP; Enteric Products, Inc, New York, NY). RESULTS: Compared with pretreatment values, IgG and IgA antibodies significantly and steadily decreased at 1 through 24 months' posttreatment in successfully treated patients. A decrease in titer of the IgA class was significantly greater than that of the IgG class at 1 to 12 months' follow-up. There was no significant decrease in titer of either antibody in all but 2 patients with eradication failure. A >/=30% decrease in titer of the IgA antibody at 6 months indicated eradication with sensitivity of 90.5% and specificity of 100%. For the IgG antibody, a 30% decrease at 12 months showed equal sensitivity and specificity. Seroreversion rates of IgG and IgA antibodies were 53% and 48% at 12 months and were 86% and 81% at 24 months, respectively. The mean periods from the completion of eradication therapy to seroreversion of IgG and IgA antibodies were 11.2 +/- 7.0 and 11.6 +/- 7.8 months, respectively (not significantly different). A higher pretreatment titer of IgG antibody was related to a longer period of seroreversion (r = 0.44). In one patient, (13)C-urea breath test-confirmed reinfection was accompanied by reappearance of significant titers of the IgG and IgA antibodies. CONCLUSIONS: A serology test is useful for evaluating eradication in children. Approximately half of patients with successful eradication remained to be IgG-seropositive and IgA-seropositive at 12 months' posttreatment. When a decrease titer in antibody is used for assessing eradication, an endpoint of >/=6 months is required. The IgA antibody may be a more convenient indicator of H pylori status than is the IgG antibody.
Adolescent↗
Disseminated Fusarium infection identified by the immunohistochemical staining in a patient with a refractory leukemia.
The difficulty and uncertainty encountered in diagnosing a systemic mycosis often lead to a delay in starting antifungal therapy. We reported a disseminated infection of multiple fungal isolates including Fusarium species during donor leukocyte transfusion (DLT) after allogeneic bone marrow transplantation in a 20-year-old woman with a refractory leukemia. Skin lesions are the feature of Fusarium and occur in the early period of the infection. In this case, during immunosuppression state after DLT, she presented with the whole body ache and erythematous lesions which appeared rapidly on her trunk and extremities. While administration of amphotericin B was started, her condition was further deteriorated and she died. Autopsy materials revealed that she had multiple fungal infection with different isolates, including Aspergillus and Candida in the brain, lung and liver, but not in the skin. With the immunohistochemical staining with specific antibody, Fusarium or Aspergillus infection was identified from the biopsy skin or autopsy brain, respectively. This rapid and specific immunohistochemical method may be useful for the diagnosis and treatment of invasive fungal infection without delay.
Adult↗
Strong immunoreactivity of platelet-derived growth factor and its receptor at human and mouse neuromuscular junctions.
Platelet-derived growth factor (PDGF) and its alpha-receptor were localized at human and mouse neuromuscular junctions (NMJs) using specific polyclonal antibodies against each, anti-PDGF-A and anti-PDGF alpha-receptor, respectively. By applying double fluorescence labeling, immunoreactivity for PDGF and its receptor was closely co-localized with acetylcholine receptors, which were identified with alpha-bungarotoxin. PDGF might be involved in the interaction between the presynaptic and postsynaptic components. This is the first demonstration of PDGF and its receptor concentrated at human and mouse NMJs.
Animals↗
G-CSF induces apoptosis of a human acute promyelocytic leukemia cell line, UF-1: possible involvement of Stat3 activation and altered Bax expression.
Granulocyte colony-stimulating factor (G-CSF) is a cytokine that regulates the proliferation, differentiation and survival of cells in the granulocytic lineage. In this study, however, we found that G-CSF or interleukin-6 (IL-6) induced UF-1, a human acute promyelocytic leukemia cell line, into apoptosis that was confirmed by morphological features and DNA fragmentation. This rare response is demonstrated for the first time with human acute promyelocytic leukemia cell line. The apoptosis induced by G-CSF or IL-6 was not preceded by terminal differentiation characterized by morphological maturation, capability to reduce nitroblue tetrazolium, or surface CD11b expression. Interestingly, Western blot analysis revealed that the stimulation of UF-1 with either G-CSF or IL-6 resulted in excessive activation of both signal transducer and activator of transcription 3alpha (Stat3alpha) and Stat3beta. Furthermore, an additional 18 kDa Bax-related protein was expressed by the stimulation of G-CSF or IL-6, while Bcl-2 and Bcl-X proteins remained unchanged. These findings suggest that UF-1 may be a valuable tool in investigating the aberrant regulation of apoptosis, especially the Stat3 involvement in the mechanism of apoptosis induction.
Apoptosis↗
Lysophosphatidic acid and mesangial cells: implications for renal diseases.
The last decade has witnessed a phenomenal increase in our understanding of the biological role of lysophosphatidic acid (LPA) and has led to an appreciation of this critical serum-derived growth factor released from platelets. We herein summarize recent observations that collectively support the hypothesis that LPA may play a key role in the pathogenesis of initiation and progression of proliferative glomerulonephritis. LPA synergistically stimulates mesangial cell proliferation in combination with platelet-derived growth factor in primary culture. The mechanism of co-mitogenesis is likely to be mediated by the prolonged activation of mitogen-activated protein kinase which is stimulated by platelet-derived growth factor and LPA through different mechanisms. LPA contracts cultured mesangial cells and has properties in common with other pressor molecules including mobilization of intracellular Ca2+ and promotion of Ca2+ entry through dihydropyridine-sensitive calcium channels. LPA receptor mRNA has been identified in isolated glomeruli dissected from renal biopsy samples of patients with IgA nephropathy. All of these facts have led us to postulate that LPA is produced within glomeruli and that LPA's mitogenic as well as haemodynamic action contribute to the pathological process of mesangial proliferative glomerulonephritis. The possible production of LPA as an autocrine factor from mesangial cells themselves has also been discussed.
Glomerular Mesangium↗
[General principles of treatment and effects of childhood intractable epilepsy].
Intractable epilepsy can be defined as (1) refractory to the treatment, (2) with frequent and severe seizures, and (3) with association of mental disability. Main disorders of childhood intractable epilepsy include Ohtahara syndrome, West syndrome, Lennox-Gastaut syndrome, severe myoclonic epilepsy in infancy, and symptomatic localization related epilepsy. Our results of long-term prognosis of West syndrome showed seizure free patients were 11 of 14 (79%) in cryptogenic and 10 of 29 (34%) in symptomatic cases. Intelligence was normal in 9 of cryptogenic (64%) and only 1 of symptomatic cases. Evolutional changes of West syndrome showed seizure free in 21, localization related epilepsy in 10, secondary generalized epilepsy in 10, unclassified epilepsy in 2. None of Lennox-Gastaut type was observed. A 13-year-old boy of tuberous sclerosis with frequent drop attacks was treated by anterior 3/4 callosotomy. Although the tonic seizures remained, drop attacks were completely abolished. The measures to the intractable epilepsy should be targeted to the symptoms or conditions to which the patients and guardians want to be eliminated.
Adolescent↗
Mutations in the E-domain of RAR portion of the PML/RAR chimeric gene may confer clinical resistance to all-trans retinoic acid in acute promyelocytic leukemia.
The binding of all-trans retinoic acid (ATRA) to the ligand-binding region in the E-domain of retinoic acid receptor-alpha modifies the transcriptional activity of RARalpha protein. ATRA probably induces differentiation of acute promyelocytic leukemia (APL) cells by binding to the E-domain of the RARalpha portion (RARalpha /E-domain) of PML/RARalpha chimeric protein. Therefore, molecular alteration in the RARalpha /E-domain of the chimeric gene is one mechanism by which patients with APL may acquire resistance to ATRA therapy. In this study using reverse transcription-polymerase chain reaction and single-strand conformation polymorphism, DNA segments amplified from the RARalpha /E-domain in fresh APL cells of 23 APL patients (8 males and 15 females from 4 to 76 years of age) were screened for mutations. Of those patients, 3 patients (1 with de novo and 2 with relapse) had clinical resistance to ATRA therapy. We found mutations in the RARalpha /E-domain of PML/RARalpha chimeric gene exclusively in the 2 patients who exhibited ATRA-resistance at relapse, whereas the mutations were not detected at their initial onset. Interestingly, these patients received a prolonged or intermittent administration of ATRA before relapse with ATRA-resistance. The mutations lead to the change of amino acid in the ligand-binding region of RARalpha /E-domain, Arg272Gln, or Met297Leu according to the amino acid sequence of RARalpha, respectively. Further study demonstrated that the in vitro ligand-dependent transcriptional activity of the mutant PML/RARalpha protein was significantly decreased as compared with that of wild-type PML/RARalpha. These findings suggest that mutations in the RARalpha /E-domain of the PML/RARalpha chimeric gene may confer clinical resistance to ATRA therapy in patients with APL.
Adolescent↗
Establishment of a novel cell line (TS-2) of pre-B acute lymphoblastic leukemia with a t(1;19) not involving the E2A gene.
The t(1;19)(q23;p13) translocation involving the E2A gene on chromosome 19p13.3 is a nonrandom translocation that is often seen in childhood pre-B-cell acute lymphoblastic leukemia (ALL). However, recent studies have demonstrated the presence of immunophenotypic and molecular heterogeneity among patients with the cytogenetically identical chromosome translocation. Here we report a novel pre-B ALL cell line, TS-2, with t(1;19) translocation not involving the E2A gene. The breakpoint of t(1;19) in TS-2 was demonstrated to be at 19p13.3, a region indistinguishable from the locus of the E2A gene, by cytogenetic study and fluorescence in situ hybridization. However, rearrangement of the E2A gene was not detected in TS-2 by Southern blot analysis. Moreover, the expressions of PBX1 or E2A/PBX1 fusion genes were not detected by an extensive study with Northern blot analysis and reverse transcription-polymerase chain reaction. These findings suggest that TS-2 may have a genetic abnormality involving uncharacterized gene(s) at 19p13.3 distinct from the E2A gene and, therefore, may be useful for investigating the heterogeneity of molecular pathogenesis in leukemias with t(1;19)(q23;p13) translocation.
Adenovirus E2 Proteins↗
Safety and efficacy of one-week triple therapy for eradicating Helicobacter pylori in children.
BACKGROUND: Proton pump inhibitor-based eradication therapy of Helicobacter pylori has been widely studied in adults, but there have been only a few reports about this therapy in children. The purpose of this study was to investigate the safety and efficacy of 1-week triple therapy for eradication of H. pylori and ulcer healing in children. PATIENTS AND METHODS: We prospectively studied 15 patients aged 2-17 years (5 with gastric ulcers, 8 with duodenal ulcers, and 2 with nodular gastritis alone). Three patients had H2 blocker-resistant duodenal ulcers. Patients received 0.75 mg/kg of lansoprazole b.i.d., 25 mg/kg of amoxicillin b.i.d., and 10 mg/kg of clarithromycin b.i.d. for 7 days. No additional therapy (including antisecretory drugs) was administered to any patients following eradication therapy. Patients underwent endoscopy to obtain antral biopsies (culture, urease test and histology) and to evaluate the mucosal status, and underwent a 13C-urea breath test before and 4-8 weeks after the completion of a 1-week course of therapy. RESULTS: All patients received the full drug regimen. Endoscopy showed complete healing of ulcers in 12 of 13 patients with peptic ulcer disease (92%). H. pylori was eradicated in 13 of 15 patients (87%). Diarrhea and/or an altered taste sensation occurred in 5 patients (33%). There were no hematological or biochemical abnormalities related to therapy. CONCLUSION: The 1-week triple therapy was safe and effective for eradicating H. pylori. The present study showed that ulcer healing in juveniles is closely associated with eradication of H. pylori, and that no additional therapy is required when H. pylori is eradicated. A shorter course of eradication therapy than 2 weeks may be suitable for children with H. pylori infection.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Acute jaundice in Vientiane, Lao People's Democratic Republic.
Analysis of serum samples from patients with acute jaundice by means of enzyme-linked immunosorbent assay and polymerase chain reaction testing provided the first profile of this condition in Vientiane, Lao PDR, in 1995 and 1996. In a case-control, hospital-based study, evidence of acute infections due to hepatitis A and B viruses was found in 14% and 10% of cases, respectively. Hepatitis E virus, however, did not appear to contribute to clinically recognized acute jaundice. Similarly, antibody to hepatitis C virus was recognized in almost equal proportions of cases (8%) and controls (6%), thus representing probable background infections. The detection of hepatitis G virus marks the first report of this virus in Lao PDR. The large proportion (21%) of new leptospiral infections in cases without acute hepatitis A or B was notable. This finding suggests significant regional underreporting of leptospirosis as a cause of acute jaundice. The limited laboratory diagnostic capabilities for confirming a differential diagnosis of leptospirosis contribute to the lack of attention paid to this important health problem.
Acute Disease↗
Helicobacter pylori reinfection rates in children after eradication therapy.
BACKGROUND: There are few studies of Helicobacter pylori reinfection in childhood. In the current study the reinfection rate of H. pylori and ulcer recurrence were investigated during a follow-up period of 12 months or more in children who had undergone eradication therapy. METHODS: Twenty-seven patients aged 5 to 16 years (6 with gastric ulcer, 13 with duodenal ulcer, and 8 with nodular gastritis) were studied. Biopsy-based H. pylori tests performed 1 to 2 months after eradication therapy demonstrated that eradication was successful in 23 patients (5 with gastric ulcer, 11 with duodenal ulcer, and 7 with nodular gastritis) and unsuccessful in 4 (1 with gastric ulcer, 2 with duodenal ulcer, and 1 with nodular gastritis). Twenty-three successfully treated patients were observed for a mean of 22 months (a total of 42.2 patient years of follow-up). To assess H. pylori status, all 23 patients underwent a 13C-urea breath test 1 year after eradication therapy. If the test result was negative, the patients underwent the follow-up test once every year thereafter. In successfully and unsuccessfully treated patients, endoscopy was performed if a patient reported symptoms suggesting ulcer recurrence. RESULTS: The initial follow-up 13C-urea breath tests showed that all 23 patients remained free of infection at 12 to 19 months. Among 17 patients, the second test confirmed reinfection in 1 at 28 months. In two patients studied, the third test showed a negative result. The reinfection rate was 2.4% per patient year. Over the follow-up period, ulcer recurrence was found in 2 of 3 ulcer patients with eradication failure but in none of the 16 ulcer patients with successful eradication. The recurrence rate was significantly lower in successfully treated patients than in unsuccessfully treated patients (p < 0.05). CONCLUSIONS: Reinfection with H. pylori is rare in children aged more than 5 years, and successful eradication significantly reduces ulcer recurrence. This study supports the benefit of eradication therapy in older children.
Adolescent↗
Heterogeneity of ictal SPECT findings in nine cases of West syndrome.
We evaluated the ictal and interictal single photon emission computed tomography (SPECT) of 9 patients with West syndrome (WS). In this group, we noted two clear patterns of cortical hyperperfusion and subcortical hyperperfusion in the ictal SPECT. Both patterns were different from the previously documented ictal patterns for complex partial seizures (CPS) or secondarily generalized seizures. Our results suggest that the tonic spasms of WS do not always have a single neurophysiological basis; e.g., patients with hemihypsarrhythmia and focal hypsarrhythmia did not show ictal hyperperfusion of the lesion with hypsarrhythmia. These findings indicate that the origin of hypsarrhythmia as an EEG feature and the origin of tonic spasms may be different in such patients. In particular, hypsarrhythmia appears to originate from cortical lesions, whereas the subcortical structures may be primarily responsible for the tonic spasms. Our report is the first published study of ictal SPECT in patients with WS.
Adolescent↗
17Beta-hydroxysteroid dehydrogenase types 1 and 2 in human placenta: an immunohistochemical study with correlation to placental development.
In estrogen metabolism, the enzymatic properties of the 17beta-hydroxysteroid dehydrogenase (17betaHSD) isozymes play very important roles in steroid hormone metabolism in various tissues, including the placenta. 17betaHSD type 1 catalyzes primarily the reduction of estrone (E1) to estradiol (E2), whereas 17betaHSD type 2 catalyzes primarily the oxidation of E2 to E1. In this study, we examined immunohistochemical localization of 17betaHSD types 1 and 2 in human placenta (31 cases) ranging from 4-40 weeks gestation. The immunoreactivity of 17betaHSD type 1 was exclusively detected in syncytiotrophoblast from 4 weeks gestation to term placenta. Immunoreactivity of 17betaHSD type 2 first appeared in endothelial cells of intravillous vessels at 12 weeks gestation, and the number of 17betaHSD type 2-positive endothelial cells markedly increased up to 19 weeks, then reached a plateau. We quantitatively evaluated the 17betaHSD type 2-positive endothelial cells in chorionic villi and determined the ratio of 17betaHSD type 2-positive endothelial cells using immunohistochemistry of CD34, an endothelial antigen, in serial mirror tissue sections and subsequent image analysis using CAS 200. CD34 was detected from 4 weeks gestation, and its positive areas continued to increase toward term. The 17betaHSD type 2-positive area per CD34-positive area markedly increased from 13 weeks gestation and reached a plateau at 19 weeks gestation, in which almost all endothelial cells were positive for 17betaHSD type 2. 17BetaHSD type 2, therefore, is considered to prevent the passage of excessive estrogens into the fetal circulation at endothelial cells of the intravillous fetal capillaries by catalyzing the inactivation ofE2 to E1.
17-Hydroxysteroid Dehydrogenases↗
Peripheral blood stem cell transplantation for hepatoblastoma with microscopical residue: a therapeutic approach for incompletely resected tumor.
We report a nine-month-old boy with stage III B hepatoblastoma of caudate lobe origin. Surgical resection was attempted following six courses of chemotherapy, but viable tumor cells remained microscopically at resection margins. Subsequently, he received peripheral blood stem cell transplantation (PBSCT), whose preparative regimen being consisted of carboplatin, etoposide, tetrahydropyranyl adriamycin, and melphalan. Since then, the patient shows no relevance of local relapse or distant metastasis without any chemotherapy. PBSCT for patients with post-operative residue may improve the outcome of advanced hepatoblastoma and worth of a further clinical investigation.
Disease-Free Survival↗
Hepatic and serum bile acid compositions in patients with biliary atresia: a microanalysis using gas chromatography-mass spectrometry with negative ion chemical ionization detection.
Hepatic and serum bile acids in five patients with biliary atresia were preoperatively determined by microanalysis using gas chromatography-mass spectrometry with negative ion chemical ionization detection. The hepatic content of total bile acids was markedly elevated (3079+/-711 nmol/g protein), most of which were primary bile acids. Accumulation of unconjugated bile acids (2.93% to 4.62% of the total) was observed in the liver tissue of these patients, although only trace amounts were detected in their sera. The ratio of glycine-conjugated to taurine-conjugated bile acids was 0.44+/-0.18 in liver tissue and 0.79+/-0.52 in serum and these values were significantly lower than those of controls. This study has shown that the composition of bile acids in serum does not reflect that in liver tissue faithfully. The accumulation of these hydrophobic bile acids may contribute to initiating or exacerbating liver injury in infants with cholestatic liver diseases.
Bile Acids and Salts↗