Surrogate light chains (lambda 5/VpreB) are selectively expressed in early precursors of B cells. B-cell defects in X-linked agammaglobulinemia (XLA) are caused by mutations in the gene for Bruton's tyrosine kinase. To elucidate the nature of early B-lineage cells in bone marrow (BM), samples from 13 XLA patients and 24 healthy controls of different ages were comparatively analyzed using an antihuman VpreB monoclonal antibody. Expression of surrogate light (SL) and mu-heavy chains were examined after cell membrane permeabilization because they are mainly expressed in the cytoplasm of early B-lineage cells. A flow cytometric analysis of normal BM identified 5 discrete cell types of B cells: mu(-)SL(++) (pro-B [B-cell progenitor]), mu(low)SL(++) (pre-B1a), mu(low)SL(+) (pre-B1b), mu(low)SL(- )(pre-B2), and mu(high)SL(- )(B). The large cells, presumably in cycling states, were enriched in pre-B1a cells. The frequencies of B-lineage cells in BM were higher in young children, and declined with advancing age. In contrast, XLA showed a profound reduction in BM B-lineage cells. In XLA BM, an expansion of pro-B cells with some small pre-B1a cells was marked, but other cells were negligible. These observations illustrate a B-cell maturation defect in XLA as well as a normal human B-cell differentiation pathway. The results suggest that the genetic defect in XLA may impede the evolution of pro-B cells beyond the earlier pre-B stage into the later stage of pre-B cells in B-cell development. (Blood. 2000;96:610-617)

Adolescent↗

PubMed2000

Gated SPET quantification of small hearts: mathematical simulation and clinical application.

Quantification of gated single-photon emission tomography (SPET) in small hearts has been considered to be inaccurate. To evaluate the validity of gated SPET in a small chamber volume, mathematical simulation and clinical application to paediatric patients were performed. Myocardium with various chamber sizes from 14 ml to 326 ml was generated assuming an arbitrary resolution (6.9-15.7 mm in full-width at half-maximum), noise and zooming factors. The cut-off frequency of the Butterworth filter for preprocessing was varied from 0.16 to 0.63 cycles/cm. The chamber volume was calculated by quantitative gated SPET software (QGS). The patients, aged 2 months to 19 years (n=27), were studied by gated technetium-99m methoxyisobutylisonitrile or tetrofosmin SPET. Image magnification as large as possible was performed during data acquisition to include the whole chest using 1.25-2.0 zooming. Based on the simulation study, an underestimation of the chamber volume occurred below a volume of 100 ml. The degree of underestimation for a 37-ml volume was 49% without zooming, but it improved to 3% with 2x zooming. Filters with a higher cut-off frequency, better system resolution and hardware zooming during acquisition improved quantitative accuracy in small hearts. For the subjects under 7 years old (n=7), quantification of volume and ejection fraction (EF) was possible in 72% of the patients. In those over 7 years old, gated SPET quantification was feasible in all cases. The correlation between gated SPET end-diastolic volume (SPET EDV) and both echocardiographic end-diastolic dimension (EDD) and echocardiographic EDV was good (r=0.84 between SPET EDV and echo EDD, r=0.85 between SPET EDV and echo EDV, P<0.0001 for both). The correlation between gated SPET EF and both echocardiographic fractional shortening (FS) and echocardiographic EF was fair (r=0.69 between SPET EF and echo FS, r=0.72 between SPET EF and echo EF, P<0.0001 for both). In conclusion, quantification of gated SPET of small hearts can be improved by means of a SPET filter with a high cut-off frequency, high system resolution and appropriate zooming. Gated SPET should be attempted not only in patients with small hearts but also in paediatric patients.

Adolescent↗

PubMed2000

Genetic evidence for a novel gene(s) involved in urogenital development on 10q26.

BACKGROUND: Although the frequent association between distal 10q monosomy and urogenital anomalies suggests the presence of a gene(s) for urogenital development on distal 10q, molecular deletion mapping has not been performed for the putative gene(s). In this study, we examined genotype-phenotype correlations in patients with distal 10q monosomy. METHODS: This study consisted of six karyotypic males (cases 1 through 6) and four karyotypic females (cases 7 through 10) with 10q26 monosomy. Cases 3 through 5 and 7 through 10 had urinary anomalies such as vesicoureteral reflux and hypoplastic kidney, and cases 1 through 6, 8, and 9 exhibited genital anomalies such as micropenis, hypospadias, cryptorchidism, and hypoplastic labia majora. Fluorescence in situ hybridization (FISH) for 10q telomere, whole chromosome 10 painting, and microsatellite analysis for 35 loci on distal 10q were performed in cases 1 through 8. RESULTS: FISH and whole chromosome painting confirmed distal 10q monosomy in cases 1 through 8. Microsatellite analysis revealed that hemizygosity for the region distal to D10S186 was shared by cases with urinary anomalies and that for the region distal to D10S1248 was common to cases with genital anomalies. Furthermore, it was indicated that PAX2, GFRA1, and EMX2 on distal 10q, in which the deletions could affect urinary and/or genital development, were present in two copies in cases 1 through 8. CONCLUSIONS: The results suggest that a novel gene(s) for urinary development and that for genital development reside in the approximately 20 cM region distal to D10S186 and in the approximately 10 cM region distal to D10S1248, respectively, although it remains to be determined whether the two types of genes are identical or different.

Adolescent↗

PubMed1999

[Chromosomal analysis in congenital malformation syndromes].

Explore the source record for details and available documents.

Chromosome Aberrations↗

PubMed1996

[Analysis of a novel gene expressed in apoptotic T-cell hybridoma treated with dexamethasone].

Developmentally and physiologically controlled cell deaths are called programmed cell death (PCD), and distinguished from accidental cell death while apoptosis is defined morphologically as a certain type of cell death (i.e. chromatin condensation, DNA fragmentation, organella compaction, and blebing of cell and nuclear membranes). Apoptosis is often associated with PCD. Most of cells undergoing PCD have been shown to require de novo synthesis of mRNA and protein. A number of genes have been reported to be expressed in apoptotic cells. In the immune system programmed cell death plays an important role in negative selection of immature T cells. Situations that result in programmed cell death include the withdrawal of cytokine from cultures of cytokine dependent cells, lysis of target cells by cytotoxic T cells, and activation of T cells. In T cells, another well described means of inducing apoptosis is an exposure to glucocorticoids. We cloned a novel gene expressed in apoptotic 2B4. 11 mouse T-cell hybridoma treated with steroid. This gene was not detected in vivo, but was so in mouse thymocytes and splenocytes cultured with dexamethasone and IgM stimulated mouse preB cell line WEHI-231. Thirty-six amino acids, position 2-37, has a 37% homology to mouse intracisternal A-particle gag p27 protein.

Amino Acid Sequence↗

PubMed1994

A case of pseudo-Bartter's syndrome due to intestinal malrotation.

Intestinal malrotation presenting beyond the neonatal period is associated with a multiplicity of symptoms, which are often non-specific and, consequently, are associated with delays in diagnosis. Pseudo-Bartter's syndrome, which mimics the manifestations of Bartter's syndrome, can be caused by a severe chloride deficiency secondary to vomiting, diarrhea, perspiration, diuretic abuse and so on. We describe a 6 year old boy who had been admitted to hospital three times during the preceding year. The patient lapsed into a critical condition with profound hypochloremia and hypokalemic metabolic alkalosis induced by extremely massive vomiting. The attacks of vomiting were spasmodic and self-limited. During the episodes of vomiting he fulfilled the criteria of pseudo-Bartter's syndrome, including hyperreninemia, hyperaldosteronism and normal blood pressure, but in the intervals between attacks he was completely asymptomatic. At the third admission, examination supported an overall clinical picture of bowel obstruction, which was confirmed by radiographic examination. Laparotomy revealed a midgut volvulus with intestinal malrotation. After surgery he made a good recovery and was symptom-free. In this patient, the high degree of hypochloremia and hypovolemia activated the renin-angiotensin-aldosterone system, then aldosterone promoted intensive reabsorption of sodium and excretion of potassium into the urine. Consequently the diagnosis of pseudo-Bartter's syndrome was establish on the basis of an extreme decrease in urinary chloride and an increase in urinary potassium concentration. It is relatively rare for vomiting due to intestinal malrotation to induce pseudo-Bartter's syndrome. The importance of considering this rare diagnosis in such cases is discussed.

Bartter Syndrome↗

PubMed1994

[Clinical study of fluconazole-injectable and -granules in pediatric patients].

In this study, we have investigated the clinical effectiveness of fluconazole (FLCZ) given intravenously or orally to pediatric patients with systemic fungal infections. FLCZ was administered intravenously to two patients with acute leukemia (multiple hepatosplenic candidiasis and aspergillosis) and orally to two mycosis complicated with neuroblastoma and aplastic anemia, respectively. Clinical efficacies were excellent and no side effects were observed in any patients. Pharmacokinetic analysis in 6 neonates revealed that the plasma half-life is 37-41 hours after administration of single dose of intravenous infusion of 3 mg/kg of FLCZ.

Administration, Oral↗

PubMedDate not supplied

Changes in peritoneal equilibration test values during long-term peritoneal dialysis in peritonitis-free children.

Little is known about the changes in peritoneal equilibration test (PET) values in children on long-term peritoneal dialysis (PD). In the present study, a PET was carried out every 6 months in 39 children (mean age 8.8 +/- 5.5 years) undergoing PD for 6 to 85 months (mean 36.9 +/- 23.1 months). Patients experiencing peritonitis were excluded. Both D/P creatinine (dialysate-to-plasma ratio of creatinine at 4 hours) and D/D0 glucose (ratio of dialysate glucose at 4 hours' dwell time to dialysis glucose at 0 dwell time) were measured 195 times in this series of patients. No remarkable change was found for D/P creatinine or D/D0 glucose during the first 24 months of PD but thereafter, D/P creatinine increased gradually and D/D0 glucose decreased gradually. Mean D/P creatinine increased significantly after the first 24 months of PD: from 0.66 +/- 0.12 during the first 24 months, to 0.70 +/- 0.09 after 25 months and more of PD (p = 0.0051). Mean D/D0 glucose decreased significantly after 24 months of PD: from 0.42 +/- 0.09 during the first 24 months, to 0.38 +/- 0.08 after 25 months and more of PD (p = 0.0015). The most significant change for both D/P creatinine and D/D0 glucose occurred after 24 months of PD. It seems reasonable to consider the mean PET values at 24 months of PD as the standard PET values.

Adolescent↗