Rapid decrease in tuberculin skin test reactivity at preschool age after newborn vaccination

A study of tuberculin sensitivity was performed in 353 children aged 4-6 years, all vaccinated at birth with British BCG vaccine. Significant waning of tuberculin reactions with increasing age was found (p < 0.05). In the age group < 4.5 years, the mean tuberculin reaction was 6.6 mm, in the age group 4.5-5.5 years 5.2 mm and in the age group of > 5.5 years 3.5 mm. The number of children with positive reactions (> or = 5 mm) was 165 (40%) and those with strong reactions (> or = 10 mm) 49 (14%). None of the latter children had active tuberculosis during a follow-up period of 12 months. Eighty-three (24%) of the children had no reaction. The children who had been revaccinated with the MPR vaccine against measles, rubella and parotitis (n = 31) had significantly larger tuberculin reactions than the non-revaccinated children. Atopic dermatitis or infections during the preceding six months did not have any significant influence on reaction sizes. Our results demonstrate that the variation in size of tuberculin reactions after BCG vaccination at birth is large. We conclude that tuberculin sensitivity wanes rapidly by the age of 4.0-6.3 years.     

Feeding during acute diarrhea as a risk factor for persistent diarrhea

Dietary intake during diarrhea in children less than three years of age was estimated from information recorded on illustrated dietary forms used by children's caretakers during the first week of illness in a prospective community-based study of diarrheal diseases in Lima, Peru. The frequency of consumption and the amount consumed of food groups and selected commonly consumed foods were analyzed by the final duration of the diarrheal episode. Cereals were less frequently consumed during the acute phase of diarrheal episodes that ultimately became persistent (>14 days'duration), apparently shortening the duration of the episode by one day (median duration of four days in children not consuming vs three days in children consuming cereals during diarrhea, p <0.02 Kaplan-Meier logrank test). Only roots and tubers (mainly potatoes) were consumed in greater quantity during episodes that became persistent. There was no evidence that consumption of breast milk or non-maternal milk was associated with an alteration in diarrheal duration. This study provides further evidence of the beneficial effects of continuing feeding during diarrhea using foods available at the home level, especially cereals, which are commonly used in the diet of young children.     

Role of Moraxella (Branhamella) catarrhalis as a respiratory pathogen in children

During a 12-month surveillance period in 1981-1982, Moraxella catarrhalis was detected in cultures from nasopharyngeal aspirates from 76 (17%) of 449 children hospitalized with middle or lower respiratory tract infection. Seroconversion to M. catarrhalis was positive in 4(5%) of the 76 patients with M. catarrhalis present in nasopharyngeal aspirates and in 4(1%) of 373 patients with a negative finding. Although children with respiratory tract infections were often colonized by the organism, this was rarely the infective agent of the middle or lower airways. Four of 8 patients with seroconversion to M. catarrhalis exhibited a concomitant RSV infection. The carriage of this species was more closely associated with parainfluenza virus infections. Serological responses to M. catarrhalis were not associated with acute otitis media, and were also rare in children with pneumonia. It is concluded that bronchopulmonary infections caused by M. catarrhalis are rare in children, and that M. catarrhalis aetiology need not be considered in the selection of antibiotics in cases of community-acquired pneumonia or other infections of the middle or lower respiratory tract affecting primarily healthy children.     

Immunity to hepatitis B, poliomyelitis and measles in fully vaccinated Aboriginal and Torres Strait Island children

Objective: To determine the immunity to hepatitis B, poliomyelitis and measles in fully vaccinated Aboriginal and Torres Strait Island children in north Queensland.
Methodology: A cross-sectional survey of immunity in a sample of children; 101 fully vaccinated Aboriginal and Torres Strait Island children, with a median age of 24.5 months, from 10 communities in North Queensland participated in this study. The main outcome measures were the prevalence of adequate antibody levels against hepatitis B, poliomyelitis and measles.
Results: Only 54% (95% Cl 44–63%) of the children had adequate immunity (10 m iu/mL) to hepatitis B, and one child had been infected despite vaccination. Although all the children (95% Cl 96–100%) had adequate immunity (i.e. neutralizing antibodies at a dilution of 1:8) to poliovirus 2, only 93% (95% Cl 86–96%) and 60% (95% Cl 50–69%) had adequate immunity to polioviruses 1 and 3, respectively. Nearly all (96%; 95% Cl 90–98%) of the children had adequate immunity (i.e. detectable IgG antibody) to measles.
Conclusions: Although a relatively low proportion of the children had adequate antibody levels against hepatitis B the clinical significance of this observation is uncertain. Further studies are needed to determine whether fully vaccinated Torres Strait Island children have been adequately protected and whether they require a booster dose of hepatitis B vaccine. A substantial proportion of fully vaccinated Aboriginal and Torres Strait Island children are inadequately protected against poliomyelitis, and therefore any such child with acute flaccid paralysis should be investigated fully for poliomyelitis. Vaccinated Aboriginal and Torres Strait Island children are well protected against measles, as are other Australian children.     

Modulating the modulators: parasites,neuromodulators and host behavioral change

Neuromodulators can resculpt neural circuits, giving an animal the behavioral flexibility it needs to survive in a complex changing world. This ability, however, provides parasites with a potential mechanism for manipulating host behavior. This paper reviews three invertebrate host-parasite systems to examine whether parasites can change host behavior by secreting neuromodulators. The parasitic wasp, Cotesia congregata, suppresses host feeding partly by inducing the host (Manduca sexta) to increase the octopamine concentration in its hemolymph. The increased octopamine concentration disrupts the motor pattern produced by the frontal ganglion, preventing the ingestion of food. Polymorphus paradoxus (Acanthocephalan) alters the escape behavior of its host, Gammarus lacustris (Crustacea), possibly through an effect on the host's serotonergic system. The trematode Trichobilharzia ocellata inhibits egg-laying in its snail host (Lymnaea stagnalis), partly by inducing the host to secrete schistosomin. Schistosomin decreases electrical excitability of the caudodorsal cells. The parasite also alters gene expression for some neuromodulators within the host's central nervous system. In at least two of these three examples, it appears that the host, not the parasite, produces the neuromodulators that alter host behavior. Producing physiologically potent concentrations of neuromodulators may be energetically expensive for many parasites. Parasites may exploit indirect less energetically expensive methods of altering host behavior. For example, parasites may induce the host's immune system to produce the appropriate neuromodulators. In many parasites, the ability to manipulate host behavior may have evolved from adaptations designed to circumvent the host's immune system. Immune-neural-behavioral connections may be pre-adapted for parasitic manipulation.     

Polymorphism of vitamin D receptor gene start codon in patients with calcium kidney stones

BACKGROUND: A linkage has been detected between vitamin D receptor (VDR) locus and calcium kidney stone disease. In order to assess the eventual role of VDR gene start codon polymorphisms in stone production, we analyzed the genotype-phenotype association in a group of patients with calcium kidney stones. METHODS: One hundred and fifty-five patients were studied. VDR genotypes were characterized at the translation start site by restriction fragment length polymorphism analysis, using endonuclease FokI. Phenotypes of calcium-phosphate metabolism were compared in patients with different genotypes: strontium enteral absorption (used as a surrogate marker for calcium absorption), bone mineral density (BMD), calcium and phosphate excretion were measured. RESULTS: Genotype distribution was not different in hypercalciuric and normocalciuric stone formers. Enteral strontium absorption, calcium excretion and BMD did not vary with the patient's genotype. Serum concentrations of phosphate (p=0.022) and renal threshold for phosphate excretion (p=0.026) were lower in patients with genotype FF (homozygous for the absence of the FokI site) than in those with genotype ff (homozygous for the presence of the FokI site). The lower phosphatemia was confirmed in FF hypercalciuric patients, but not in normocalciuric ones. Serum concentrations of phosphate and calcitriol in the group of hypercalciuric patients were inversely correlated with the genotype FF. CONCLUSIONS: The FokI genotype does not appear to be involved in the causes of idiopathic hypercalciuria and kidney stones. Hypercalciuric patients with FF genotype may be a subgroup with low plasma concentrations of phosphate, predisposed to tubular leakage of phosphate.     

Lactacystin, a specific inhibitor of the proteasome, induces apoptosis and activates caspase-3 in cultured cerebellar granule cells

The multicatalytic protease complex or proteasome is a fundamental nonlysosomal tool that the cell uses to process or degrade proteins at a fast rate through the ubiquitin and ATP-dependent proteolytic pathway. Examples of these important proteins include the tumor suppressor protein p53, various cyclins, the cyclin-dependent kinase inhibitor p27, NFkappaB, IkappaB, c-fos, and c-jun. The activation of proteolytic enzymes, including certain cystein-proteases of the ced-3/ICE (interleukin-1beta-converting enzyme) family, is a characteristic feature of the apoptotic program. However, the role of the multicatalytic protease complex in apoptosis is not well known. In order to obtain further information regarding the participation of the ubiquitin-mediated pathway in the decision of the cell to execute the cell death program, we have used a specific inhibitor of the multicatalytic protease complex, lactacystin, in cultured cerebellar granule cells. Cells were obtained from the cerebellum of 6- to 8-day-old Wistar rats and cultured in Neurobasal medium supplemented with B-27. Addition of lactacystin to the cultures induced apoptosis of the granule cells in a time-dependent fashion. The morphological changes produced by the proteasome inhibitor included nuclear condensation and DNA fragmentation measured by the diphenylamine test, as well as a positive labeling by the TUNEL (terminal deoxynucleotidyltransferase mediated-dUTP nick end labeling) assay, all of them typical features of apoptosis. Concomitant with apoptosis, there were changes in the expression of the ubiquitin mRNA, a progressive depletion in the free ubiquitin pool, and an increase in the high molecular weight ubiquitin-protein conjugates. Caspase-3, a member of the ced-3/ICE family of cystein-proteases, showed a marked increase in activity in the lactacystin-treated cells. In flow cytometry studies, the amount of cells in the S phase of the cell cycle was smaller in the lactacystin-treated cells than in controls, suggesting that apoptosis could be due, in part, to an alteration of the cell cycle.     

老年性骨质疏松所致骨折患者血清钙磷和TGF-β 1分析

1临床资料2003-06／2004—12收治髋部骨质疏松性骨折患20(男14，女6)例，年龄58—80(平均68．5)岁，股骨颈骨折13例，粗隆间骨折7例．对照组为老年性骨关节病或颈腰椎病患20例．均抽空腹静脉血4mL，3000r／min离心5min分离血清，4h内测定血清钙、磷，留血清-20℃保存备用，测定TGF-β1．用Au-2700全自动生化分析仪测定血清钙、磷，试剂由日本欧林巴斯公司提供．血清TGF-β1检测采用ELISA法，     

胰岛素样生长因子-I和人绒毛膜促性腺激素对成年大鼠Leydig细胞葡萄糖转运蛋白基因表达调控

目的:研究胰岛素样生长因子I(IGF I)和人绒毛膜促性腺激素(hCG)对成年大鼠睾丸Leydig细胞中葡萄糖转运蛋白(GLUT)基因表达的影响,为进一步探讨Leydig细胞中睾酮的合成、分泌与葡萄糖代谢的关系提供依据。方法:采用改良的Klinefelter方法从成年大鼠睾丸中分离获得Leydig细胞;用反转录聚合酶链技术检测IGF I和hCG对原代培养的Leydig细胞中GLUT基因表达的调控作用。结果:分离得到纯度为98%的大鼠Leydig细胞,并与对照组比较,hCG可显著增加Leydig细胞中GLUT8基因mRNA的表达水平(P<0.001),且此作用具有剂量依赖性与时效性。当在试验组细胞中单独加入IGF I或IGF I和hCG作用于细胞后,发现IGF I(100ng mL)可显著增加Leydig细胞中GLUT8基因mRNA的表达(P<0.01),也可与hCG协同作用显著提高GLUT8基因的mRNA表达,该结果与IGF I(100ng mL)和hCG(10ng mL)能协同作用极显著增加睾酮合成水平(P<0.001)的结果是相吻合的。在大鼠Leydig细胞中,无论10ng mL或100ng mL还是两者同时作用于细胞,都不能影响GLUT1和GLUT3基因的mRNA水平。结论:在成年大鼠Leydig细胞中,IGF I和hCG对细胞中的GLUT8基因表达的调节作用具有特异性,其协同作用能显著提高细胞中GLUT8基因mRNA水平,增强细胞摄取葡萄糖的能力,给细胞提供更多的代谢能源,最终增加Leydig细胞睾酮的合成与分泌。     

Role of nuclear medicine in the treatment of malignant gliomas: the locoregional radioimmunotherapy approach

The high-grade malignant gliomas (anaplastic astrocytomas and glioblastoma) have a very bad prognosis since the available methods of treatment (surgery, radiotherapy and chemotherapy) are unable to control the progression of the disease for long. The use of specific monoclonal antibodies labelled with a suitable isotope (iodine-131 or yttrium-90) represents an effective approach to hamper tumour regrowth. Some authors have injected the antibodies intravenously, or have tried to increase the tumour/background ratio with the avidin/biotin system. In many cases the labelled monoclonal antibodies were injected directly into the tumoral bed after the operation. The authors' experiences concern a quite large locoregional radioimmunotherapy study which was performed by using antitenascin antibodies labelled initially with 131I and more recently with 90Y. The clinical results demonstrate the ability of this technique to control, for a long time, the growth of these tumours. The glioblastoma median survival was prolonged to 25 months (131I group) or 31 months (90Y group). The response rate (which comprises PR, CR and NED) was 47.1% (glioblastoma 131I group) or 40% ( glioblastoma 90Y group). In many cases a significant tumour shrinking effect was radiologically demonstrated. The use of 90Y proved more favourable in bulky lesions, and reduced the radioprotection problems.