Antistreptolysin levels in normal infants and young children

A modified method of estimating the antistreptolysin O titre (A.S.O.) is described. The A.S.O. of 279 sera from normal children under 5 years of age is recorded, together with that of 40 children over 5 years of age. The results show a range much lower than that found in adults and older children and are discussed with respect to estimations made in children with proven infections. The significance of these findings is discussed.     

正常儿童的神经电图检测报告

目的:利用神经电图检测技术,获取不同年龄期正常儿童的有关神经电生理数据,以便在儿科临床应用中提供其详细、有效的判断依据。方法:采用肌电图／诱发电位仪检测405名儿童的正中神经、尺神经、腓神经、胫神经的运动传导速度(MCV)和感觉传导速度(SCV)、F波及股神经运动潜伏期(FML)。此405名正常儿童按年龄分15组,每组25-40人,分别检测双侧肢体,取单肢结果统计制表。结果:各年龄期各检查项目波形引出率100％。MCV、SCV随年龄增加而增快,潜伏期随年龄增加而延长。除胫后神经感觉神经动作电位(SNAP)随年龄增加而降低外,其余神经复合肌肉动作电位(CMAP)、SNAP波幅均随年龄增加而增高。F波潜伏期随年龄增加而延长,F波响应率无明显年龄规律,但各神经中以胫神经响应率最高,腓总神经响应率最低。结论:不同年龄儿童MCV、SCV、F波、FML的测值与年龄的增长相关,在临床应用中,应参照相应年龄期正常值作出判断。     

Regulatory function of normal monocytes in the in vitro immunoglobulin production

Induction of the immunoglobulin production by pokeweed mitogen (PWM) and S. aureus. Cowan I has been evaluated in cultures of human peripheral blood mononuclear cells gradually depleted of adherent cells. Partial depletion cells (monitoglobulins while almost complete depletion caused decreased production. These results suggest that an optimal balance of monocytes to lymphocytes is essential in the triggering of immunoglobulin production by human mononuclear cells (MNC) in vitro and that normal monocytes, when in excess, suppress in vitro differentiation of B lymphocytes into immunoglobulin secreting cells.     

Prevention of pneumococcal infection in a patient with normal immunoglobulin levels but impaired polysaccharide antibody production.

BACKGROUND: Patients with normal immunoglobulin levels may have an impaired response to immunization with pneumococcal vaccine and increased susceptibility to infection with encapsulated organisms. In children, but not adults, immunoglobulin replacement has been shown to be effective in reducing the infection rate. OBJECTIVE: To reduce the incidence of infection in an adult with impaired response to pneumococcal vaccine but normal serum IgG levels. METHODS: Intravenous IgG, 350 mg/kg, was given every 4 weeks. RESULTS: The patient, who was hospitalized 3 times in 3 years with respiratory tract infections and who had documented infection with Streptococcus pneumoniae and Haemophilus influenzae, did not require antibiotic therapy for more than 15 months while undergoing intravenous immunoglobulin replacement therapy. CONCLUSION: Adults with impaired response to vaccination with polyvalent pneumococcal vaccine and normal IgG levels may benefit from replacement therapy.     

Intracellular immunoglobulin production in vitro by lymphocytes from patients with hypogammaglobulinaemia and their effect on normal lymphocytes.

The ability of peripheral blood lymphocytes from twenty-two patients with late onset (acquired or common variable) hypogammaglobulinaemia to produce immunoglobulin was assessed by the immunofluorescent detection of intracytoplasmic immunoglobulin (Ic-Ig) in cultures stimulated with pokeweed mitogen (PWM). Intracellular immunoglobulin was found in 4-9-26% of cultured cells from eighteen out of nineteen controls. In contrast nineteen out of twenty-two patients with hypogammaglobulinaemia showed values less than 1% and in ten no Ic-Ig was detected. Two of the remaining three patients showed normal values. Lymphocytes from eleven patients showing less than 1% positive cells were selected for mixture experiments. Lymphocytes from five of the eleven patients strongly depressed immunoglobulin synthesis by normal lymphocytes when mixed together in the presence of PWM. However, lymphocytes from these individual patients did not depress immunoglobulin production in all normal controls.     

Intracellular interferon-gamma (IFN-gamma) production in normal children and children with atopic dermatitis

A reduction in the in vitro production of IFN-gamma has been consistently described in atopic dermatitis (AD). Whether this reduction is due to a decrease in the population of peripheral blood mononuclear cells (PBMC) producing IFN-gamma or reduced IFN-gamma production per cell, or a combination of both is not clear. We have examined the intracellular production of IFN-gamma in children with AD and in healthy non-atopic controls. As Staphylococcus aureus colonization is a feature of childhood AD, and is postulated to contribute to the cutaneous inflammation in atopic dermatitis, S. aureus and Staphylococcal enterotoxin B (SEB) were used to activate PBMC. Stimulated PBMC from subjects with AD had significantly fewer IFN-gamma-containing cells in response to SEB (P < 0.001) and S. aureus (P < 0.01) than normal non-atopic children. In addition, SEB-stimulated PBMC from children with AD had less IFN-gamma per cell than normal non-atopic children (P < 0.01). Reduction in the proportion of cells containing IFN-gamma was seen in CD4+, CD8+ and natural killer (NK) cells in PBMC from children with AD. Our findings indicate that reduced production of IFN-gamma observed in childhood AD is due to both a decrease in the number of IFN-gamma-producing cells and a reduced amount of IFN-gamma production per cell. Furthermore, we found that this defect was not confined to CD4+ T cells, suggesting a more generalized defect in IFN-gamma production in childhood AD.     

Bacteriostatic enterochelin-specific immunoglobulin from normal human serum.

Heat-inactivated normal human serum produces iron-reversible bacteriostasis of a number of microorganisms. This inhibitory effect was abolished by adsorption of serum with ultraviolet-killed cells of species that produce the siderophore enterochelin. Bacteriostasis also was alleviated by adsorption of serum with 2,3-dihydroxy-N-benzoyl-L-serine, a degradation product of enterochelin, bound to the insoluble matrix AH-Sepharose 4B. The adsorption process did not add iron or enterochelin to serum, nor did it remove transferrin. The immunoglobulin fraction from normal human serum was isolated; when added to a defined medium (M199) prepared so as to mimic normal human serum, the immunoglobulin rendered the medium inhibitory to an enterochelin-defective strain of Salmonella typhimurium. Adsorption of this medium with AH-Sepharose 4B-2,3-dihydroxy-N-benzoyl-L-serine removed the inhibition. Our results indicate that enterochelin-specific immunoglobulins exist in normal human serum. These immunoglobulins may act synergistically with transferrin to effect bacteriostasis of enterochelin-producing pathogens.     

Human intravenous immunoglobulin modulates monokine production in vitro.

The effects of human immunoglobulin preparations for intravenous use (IVIg) on in vitro-induced monokine production were studied. Individual peripheral blood monocytes, obtained from healthy blood donors, which produced interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) after in vitro stimulation, were identified by cytokine-specific monoclonal antibodies (mAb) and indirect immunofluorescence technique. Lipopylosaccharide (LPS) or Borrelia burgdorferi spirochetes (Bb) were used to induce TNF-alpha and IL-6 production in cultures. Peak synthesis occurred 2.5 hr after initiation of the cultures in the majority of the monocytes, but not at all in lymphocytes. The monocytes were identified by two-colour staining using a monocyte-specific mAb. IL-6 was produced by 64 +/- 8% or 71 +/- 9% (means +/- SD) of the non-IVIg-exposed monocytes after LPS or Bb stimulation, respectively (n = 12). A dose-dependent and significant reduction of the number of IL-6-producing cells was noted in the IVIg-supplemented cultures (P less than 0.003). In these cultures 24 +/- 12% or 29 +/- 12% of the monocytes made IL-6 in response to LPS or Bb. Kinetic studies indicated a sustained significant inhibition of IL-6 production during 24 hr of culture (P less than 0.001). In contrast, TNF-alpha synthesis was not inhibited by IVIg. LPS or Bb stimulation resulted in 47 +/- 18% or 69 +/- 7% TNF-alpha producing cells versus 48 +/- 9% or 59 +/- 8% in IVIg-supplemented cultures. These results indicate down-regulation of IL-6, but not TNF-alpha production, by IVIg. A direct antigen neutralization is an unlikely explanation for the divergent effects observed on monokine production after IVIg addition.     

Structures mimicking sex cord-stromal tumours and gonadoblastomas in the ovaries of normal infants and children

A chance finding of structures resembling gonadoblastomas in the ovaries of a child with lissencephaly prompted a detailed review of all ovarian histology obtained at autopsy over a 12 month period. Fifty-five stillbirths, infants and children were studied ranging from 20 weeks gestational age to 2.5 years post-natal age. In 19 infants structures mimicking gonadoblastomas and sex cord tumours with annular tubules were seen. In all but one case these structures were found in association with follicular cysts and they closely resembled the atretic follicles often seen in the stroma surrounding the follicular cysts. They differed from the atretic follicles only by virtue of their being larger. In addition, in several infants structures resembling Sertoli cell tubules or clusters of Leydig cells were found. When present, these structures always co-existed with sex cord tumours with annular tubules and gonadoblastoma-like lesions. The abnormal stromal lesions and follicular cysts were found most frequently at the stage of development when a massive 'physiological' reduction of oocytes occurs. It is suggested that the 'abnormal' structures identified in this report represent the 'first hit' of oncogenesis and could serve as the precursor of many of the sex cord-stromal tumours, and possibly germ cell neoplasms, seen in childhood.     

Standard bone-age of infants and children in Korea.

To evaluate the developmental status of children and adolescents, a bone-age chart based on the radiograph of hand and wrist has been used in many countries. Bone-age reflects not only the functional status of various hormones but also the influence of chronic disease and it has been used more widely than other indices such as the height-weight-age table. As a standard bone-age chart has not been established in Korea, a foreign bone-age chart has been used in clinics. To make a Korean standard bone-age chart, we took the radiographs of the left hand of about 5,400 children covering the whole country, and 3,407 radiographs of 1,830 boys and 1,577 girls ranging from two months to 16 years of age were selected and analyzed for bone maturity scores by the TW2-20 method. The range of ages were divided into 27 groups, and the radiographs of 50th percentile score were chosen as the standard bone-ages for the median age of each group. The youngest and oldest chronological age which had the same TW2-20 score of the standard bone-age were decided as the range of variation from the median age. We hope that a Korean standard bone-age chart can be used as the radiological index in the evaluation of the developmental status in Korean children and adolescents.     

Determination of normal human fetal immunoglobulin M levels.

Immunoglobulin M (IgM) levels were measured in 198 cord blood samples from 192 apparently normal pregnancies from 24 weeks of gestation to term. Simple linear regression analysis yielded a standard curve for IgM development during pregnancy showing a 0.5 mg/dl increase in IgM per week of gestation. This curve allows the comparison of fetal IgM levels from pregnancies considered to be at risk for intrauterine infection.     

Receptors for immunoglobulin and complement on sheep RBC-binding lymphocytes in newborn infants.

Sheep erythrocyte-binding human peripheral blood lymphocytes bearing receptors for the Fc-part of IgG and/or complement were studied in twenty newborn pre-term and term infants and fifteen adult controls. A technique with mixed rosettes and fluorescein-labelled sheep erythrocytes was used. The newborn infants had a significantly lower proportion of lymphocytes with receptors for sheep erythrocytes and the Fc-part of IgG (1.6%) than the adults (6.7%). Also the percentage of lymphocytes binding both sheep erythrocytes and complement-coated indicator cells was significantly lower in the newborn infants (2.6%) than in the adults (8.9%). A significantly higher proportion of lymphocytes had receptors for sheep erythrocytes and complement than for sheep erythrocytes and the Fc-part of IgG in both newborn infants and adults. There was no correlation between the values of lymphocytes binding sheep erythrocytes, or the Fc of IgG or complement and the proportion of mixed rosettes.     

Prevention of immunoglobulin production by allotype-dependent T cells.

Adoptive lymphocyte transfers between Iga, Igb and Igd allotype-congenic mouse strains revealed host barriers against the production of certain donor allotypes. First, as recipients of Igb cells, Iga and Igd mice permitted the production of donor Ig-4b but not that of Ig-1 b. The apparent mediators of this Ig-1 b barrier were T cells specific for Ig- 1 b determinants on B cells. Additional cell transfers showed Iga mice to have a second barrier against allotype production by Igd donor cells. Reciprocal cell transfers showed Igb and Igd mice to have comparatively weak barriers against Iga-producing cells. As host barriers were absent in mice deficient for T cells (athymic nude mice), it appears that they are T cell-mediated. Further, the allotype-dependence of such barriers means that the antigens responsible must be under the control of allotype-linked genes. The regulatory implications of this for the immune system are discussed.