ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

A variant of hepatitis B virus (HBV) having a specific mutation within the S gene has been found to infect vaccinees. To know whether similar variants were involved in Japan, we analyzed two cases of maternal transmission of HBV in infants immunized with hepatitis B immune globulin and hepatitis B vaccine. DNA clones of HBV S genes were propagated from patients and family members and sequenced. In one family, the DNA clones from the baby patient had a Gly-to-Arg mutation at the 145th codon of the S gene, whereas those from her mother had no such mutations. In the other family, all the DNA clones obtained from the two infected children had the 145th codon intact, but they had a missense mutation at the 126 th codon of the S gene, causing an amino acid substitution of Asn for Thr or Ile. This same mutation was observed in 12 of 17 clones of DNA obtained from their mother. In comparison with the wild type HBV-derived hepatitis B surface antigen, the two types of S gene mutations, either at the 145th or the 126th codon, were associated with a significant decrease in the antigenicity of some determinants on the hepatitis B surface antigen, measured by MAb. Amino acid substitution at these sites, therefore, would have induced the escape from conventional vaccines that were S gene products of wild type HBV and also from hepatitis B immune globulin, whose main components were probably also antibodies against the S gene products expressed by wild type HBV. (Pediatr Res 32: 264–268, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The influence of recombinant interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF) on IL-4-induced proliferation of postnatal human thymocytes from eight children with Down syndrome (DS, trisomy 21) and 18 control children was evaluated. DS thymuses were studied because they are characterized by cortical depletion and abnormal thymocyte differentiation. IL-4, without mitogen, induced a dose-dependent proliferation of both DS and control thymocytes. The proliferation was comparable to that induced by IL-2 and far greater than the proliferation mediated by IL-1β in the absence of mitogen. The level of IL-4 responsiveness correlated with the proportion of cells expressing the γ,δ chains of the T cell receptor. Furthermore, thymocyte preparations greatly enriched for T cell receptorγ,δ-bearing cells were found to vigorously proliferate when treated with IL-4. Both IFN-γ and TNF inhibited IL-4-driven proliferation in a dose-dependent manner, but DS thymocytes were found to be significantly more sensitive to inhibition by both cytokines. Our studies suggest an important role for IL-4 in the proliferation of T cell receptorγ,δ+thymocytes and demonstrate regulatory functions for IFN-γ and TNF in human thymocyte proliferation. The increased sensitivity of DS thymocytes to IFN-γ and TNF may explain anatomical abnormalities in DS thymuses and suggests the involvement of genes encoded on human chromosome 21 in the responses to both IFN-γ and TNF. (Pediatr Res 32: 269–276, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Two novel cytokines, stem cell factor (SCF) and PIXY321 (a fusion protein, granulocyte macrophage colony-stimulating factor + IL-3), have recently been demonstrated to enhancein vitroadult myelopoiesis. In this study, we compared the success of separating very early hematopoietic progenitor cells (CD34+) from both cord blood (CB) and adult bone marrow (ABM) and their differential response to SCF, PIXY321, and other later-acting colony-stimulating factors (CSF). Briefly, CD34+cells were isolated from CB and ABM with an anti-CD34 MAb, HPCA-1, and incubated with various combinations of SCF, PIXY321, and other CSF. The percentage of CD34+cells was decreased in CB compared to ABM before separation (0.54 versus 1.71%) (p= 0.05). Isolated CD34+cells from CB and ABM were similar in lineage with respect to CD38, HLA-DR, CD33, and CD5, but decreased in CB with respect to B-lineage expression (CD19, CD10, and CD22) (p= 0.05). SCF increased colony forming unit-granulocyte-macrophage (CFU-GM) formation from CB CD34+cells compared to unconditioned media and had a significant additive increase with IL-3 (p= 0.006) and granulocyte colony-stimulating factor (p= 0.03). SCF also had an additive increase in CB CFU-GM formation with PIXY321 (p= 0.007). PIXY321 had a similar increase in CFU-GM formation from both CB and ABM CD34+cells compared to the combination granulocyte macrophage colony-stimulating factor + IL-3. When SCF was added to IL-3, PIXY321, or PIXY321 + IL-6, there was an increase in CFU-GM from CB versus ABM CD34+cells. The combination of SCF + IL-3 + IL-6 induced the highest increase in CFU-GM formation from CB CD34+cells. These data suggest that isolated CD34+cells in CB are significantly enhanced in response to early-acting CSF (SCF), especially when used in combination with late-acting CSF. These results may have implications in theex vivoexpansion of CB progenitor cells and the modulation of neonatal hematopoiesis. (Pediatr Res 32: 277–281, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The response of hematopoietic progenitors to the growth promoting effects of hGH and IGF-I has been documented. In this study, the effects of recombinant hGH and IGF-I on the growth of circulating erythroid burst forming cells (BFU-E) from growth-IGF-I retarded children with insufficient growth hormone secretion (IGHS) were evaluated and compared with values obtained from either children with short stature and normal growth hormone levels (SNGH) or normal donors. Both recombinant hGH and IGF-I had significantly greater stimulatory effects on the growth of BFU-E from the IGHS compared with the SNGH and with the normally growing children. At its optimal concentration of 200 μg/L, recombinant hGH had a stimulatory effect on the growth of BFU-E from 11 IGHS children yielding a mean ± SD value of 2.0 ± 0.3-fold above the unstimulated controls compared with 1.45 ± 0.16-fold and 1.36 ± 0.04-fold stimulation of BFU-E from six SNGH and five normal donors, respectively. Similarly, IGF-I, at its optimal concentration of 0.065 nmol/L (0.5 ng/mL), stimulated IGHS-derived BFU-E growth 1.67 ± 0.25-fold above unstimulated controls, compared with 1.28 ± 0.17-fold and 1.3 ± 0.1-fold stimulation of BFU-E from SNGH and from normal donors, respectively. The hGH- and IGF-I-induced stimulatory effects could be neutralized by their respective specific MAb. This significantly increased reactivity of erythroid progenitors from growth-retarded IGHS children to the erythropoietic effects of hGH and IGF-I may be the result of increased availability of cell surface receptors to these hematopoietic “synergistic” factors, secondary to their ambient decreased circulating concentrationsin vivo.In vitrostudies of peripheral blood BFU-E responsiveness to hGH and to IGF-I may be useful in implicating these peptides in growth retardation and possibly in predictingin vivoresponse to them. (Pediatr Res 32: 282–285, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Premature infants have higher circulating concentrations of growth hormone (GH) than term infants. Previous investigations of these differences have used sampling frequencies of every 30 min with subsequent application of pulse detection algorithms, such as the CLUSTER program, to assess serum GH pulse parameters. To determine differences in GH secretory rates or GH t1/2values between premature and term infants, we have sampled 11 neonates at 15-min intervals. We performed deconvolution analysis of the resultant plasma GH values to estimate GH secretory and clearance parameters. Five premature infants (gestational age range 24–34 wk) and six term infants (gestational age range 38–42 wk) were sampled every 15 min for 6 h. All subjects had indwelling arterial catheters. GH was measured (in duplicate) by RIA using 10 μL of plasma. Premature infants had higher secretory burst amplitudes (2.2 ± 0.13 μg/L/minversus1.4 ± 0.27 μg/L/min,p= 0.02), higher production rates (product of the total number of bursts and the mean mass of GH secreted per burst, 811 ± 173 μg/L/6 h versus 283 ± 77 μg/L/6 h,p= 0.03), and a higher mass of GH per secretory burst (106 ± 25 μg/Lversus38 ± 11 μg/L,p= 0.049) than term infants. The integrated plasma GH concentration exhibited a strong trend toward a higher value in the) premature infants (18 100 ± 800μg/Lversus10 200 ± 2 700 μg/L,p= 0.067). There were no differences between GH secretory burst frequency (7.8 ± 0.2 pulses/6 hversus7.7 ± 0.6 pulses/6 h), GH t1/2, (20 ± 4 minversus24 ± 6 min), half-duration of burst (the time elapsed at half-maximal amplitude, 45 ± 11 min versus 25 ± 4 min), or mean interval between peaks (48 ± 2 minversus48 ± 3 min) comparing the premature and term groups, respectively. In summary, we have demonstrated an elevation in GH secretory burst amplitude, GH production rate, and the mass of GH secreted per burst in premature compared with term infants. Because the estimated GH t1/2, is similar between these two groups, amplified secretion rather than decreased clearance accounts for the differences in circulating GH concentrations. We suggest that the augmented GH secretory activity in premature infants reflects an increase in hypothalamic GH-releasing hormone activity and/or reduced somatostatin tone. (Pediatr Res 32: 286–290, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Altered IGF activity may be one mechanism involved in the pathogenesis of intrauterine growth retardation (IUGR). We assessed the expression of IGF, IGF binding protein (IGFBP), and IGF receptor transcripts in liver, carcass, and placenta of fetal rats with IUGR resulting from unilateral uterine artery ligation. We found that uterine artery ligation on d 17 of gestation resulted in reduced body weight, liver weight, and placental weight on d 20 in the fetuses from the ligated uterine horn (UA-lig) compared with those from the opposite, nonligated uterine horn (UA-nonlig) and those from dams with no surgery or anesthesia. As assessed by solution hybridization, UA-lig fetuses exhibited significantly higher hepatic IGFBP-1, IGFBP-2, and IGF-II transcript abundance than UA-nonlig controls (increased 110,50, and 31%, respectively). The only major difference among groups in carcass and placenta mRNA abundance was a 44% decrease in placental IGF-II expression in UA-lig pups compared with pups from dams that had had no surgery or anesthesia. Serum IGFBP, analyzed by ligand blot, showed a 2.4-fold increase in the doublet IGFBP-1/-2 band in UA-lig fetuses. Serum immunoreactive IGFBP-2 was unchanged among the groups, indicating that IGFBP-1 accounted for the increase in doublet intensity. Our results suggest that increased serum IGFBP-1 concentrations may decrease IGF activity in serum and thus inhibit IGF-stimulated cell proliferation or, by crossing the endothelial border, inhibit the activity of locally produced IGF. Decreased IGF-II expression in placenta also may contribute to decreased placental growth and, in turn, to IUGR. Our observations, therefore, suggest that IUGR in fetal rats with restricted arterial blood supply may be, in part, due to decreased IGF bioavailability and activity. (Pediatr Res 32: 291–295, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Total somatomedins from milk of bovine somatotropin-treated cows were isolated and characterized to determine the relative amount of the three amino acid N-terminally truncated form of IGF-I (destripeptide IGF-I). The somatomedin fraction was isolated using organic solvent and solid-phase extractions followed by preparative reverse phase HPLC and affinity chromatography. The overall yield of IGF-I was 28%, and destripeptide IGF-I was recovered with similar efficiency. The isolated somatomedins were resolved by capillary zonal electrophoresis and identified using recombinant somatomedin standards. The concentration of destripeptide IGF-I relative to full length IGF-I was determined by amino terminal sequencing and by bioassay. Results from these experiments indicated that the level of destripeptide IGF-I in milk from somatotropin-treated cows was less than 3% of the IGF-I concentration. Destripeptide IGF-I is therefore a minor component of the somatomedins present in milk from treated cows and does not contribute significantly to the proliferative activity of this milk. (Pediatr Res 32: 296–300, 1992)

ISSN:0031-3998    

出版商:OVID    

年代:1992

数据来源: OVID