Glucose-6-phosphatase in tubular endoplasmic reticulum of hepatocytes.

The histochemical localization of glucose-6-phosphatase activity in neonatal mouse liver was studied under electron microscopy. The activity was demonstrated in the tubular endoplasmic reticulum, which pervades the glycogen areas of the cell during glycogenolysis. Activity was also demonstrated in the nuclear envelope and ergastoplasm.

Mechanisms and immunomodulatory properties of pre- and probiotics.

The human body is exposed to many xenobiotic, potentially harmful compounds. The intestinal immune system is crucial in protecting the human body from these substances. Moreover, many microorganisms, residing in the gastrointestinal tract, play an important role in modulating immune responses. Pre- and probiotics may have beneficial effects on the microbial composition and activity within the human gut, subsequently affecting the immune system. Prebiotics can exert their effects via different mechanisms, like selectively stimulating the growth of bacteria by providing substrates or via direct immune stimulation. Probiotics may have beneficial health effects via competition with pathogens for substrates and binding intestinal sites, bioconversions of for example sugars into fermentation products with inhibitory properties, production of growth substrates like vitamins for the host, direct antagonism of pathogens via antimicrobial peptide production, reduction of inflammation and stimulation of immune cells. This review focuses on the different mechanisms via which the pre- and probiotics exert their beneficial effects on the host, addressing their immunomodulatory properties in particular.

Does early intervention in infants at high risk for a developmental motor disorder improve motor and cognitive development?

Infants at high risk for developmental motor disorders are in general referred to early intervention (EI) services. It is a matter of debate to which extent EI may facilitate outcome in various developmental domains. We reviewed the effects of EI programmes aiming at promoting motor and cognitive development. With respect to motor development the data indicated that EI prior to term age probably is most effective when it aims at mimicking the intrauterine environment; after term age general developmental programmes probably are most effective. Some evidence was provided that EI prior to term age has a beneficial effect on cognitive development regardless the type of intervention which is applied. After term age only general developmental programmes seemed to have an effect on cognitive development. The review concludes with preliminary data on the effect a new intervention programme, COPCA, applied between 3 and 6 months corrected age on developmental outcome till 18 months. The results indicated that COPCA was more beneficial for the development of sitting behaviour and cognition than traditional paediatric physiotherapy.

The effect of viruses on the ability to present antigens via the major histocompatibility complex.

We describe viral pathogens that cause significant human disease by their ability to interfere with the expression of major histocompatibility complex class I and II molecules. Herpesviruses and papillomaviruses encode gene products that interfere with the class I pathway of antigen processing and/or peptide translocation. Adenoviruses encode unique gene products that interfere with transport of class I molecules. Influenza virus, measles virus, and HIV interfere with the class II pathway by either suppressing the production of class II molecules or impeding antigen trafficking. Cytomegalovirus interferes with both class I and class II pathways. Better understanding of these mechanisms may lead to further insight into the pathogenesis of viral infections and allow for improved treatments.

Correlation of clinical parameters and immunological function with human immunodeficiency virus plasma viremia in children.

Studies of immune function in human immunodeficiency virus (HIV)-infected children are important, because functional abnormalities can precede CD4+ T-cell loss and are associated with the development of opportunistic and bacterial infections. We sought to correlate clinical parameters and immunological function with HIV RNA plasma levels in 20 children. HIV RNA levels were measured by a polymerase chain reaction assay. We analyzed T-cell responses to mitogens (phytohemagglutinin, concanavalin A, and pokeweed [PWM]) and antigens (tetanus toxoid and Candida albicans); T-cell suppressor activity; and humoral immunity to Haemophilus influenzae, hepatitis B, tetanus, and diphtheria vaccines. The median age of the children was 6 years. Eight children had HIV RNA levels less than 200 to 9621 copies per milliliter (group I). Four children had 37,970 to 82,630 copies per milliliter (group II). Eight children had 102,100 to 191,200 copies per milliliter (group III). There were no differences in the HIV-related complications between group I and II children. Group I/II children had significantly higher CD4+ T-cell counts (P = 0.02), less symptomatic HIV disease (P = 0.005), and more detectable protective vaccine immunity (P = 0.014) compared with group III children. Responses to mitogens were conserved in most children. Group I children tended to have higher responses to tetanus toxoid than group II children and significantly higher responses than group III children (P = 0.01). Group I had significantly higher responses to C. albicans than groups II (P = 0.016) and III (P = 0.001). Group I/II children tended to have lower suppressor activity compared with group III children (median, 0 vs 64%). We demonstrated that humoral and cellular immune dysfunction exists at all stages of disease in HIV-infected children but was most severe in children with greater than or equal to 100,000 HIV RNA copies per milliliter. Function was the most intact in children with less than 10,000 copies per milliliter.

Correlation of in vitro T-cell and B-cell function with responses to childhood vaccines in children with human immunodeficiency virus infection.

We analyzed T-cell responses to mitogens and antigens and B-cell differentiation in response to T-cell dependent (TCD) and independent stimuli in 22 human immunodeficiency virus (HIV)-infected children (1 to 9 years of age) according to the presence of protective humoral immunity at a mean time of 18 months after vaccination with Haemophilus influenzae type b, hepatitis B, diphtheria, and tetanus vaccines. The 17 vaccine responders had a mean of 3.2 responses. However, their antibody levels were lower compared with healthy children. The 5 nonresponders had a mean of 0.84 responses. There were no significant differences between responders and nonresponders regarding age, Centers for Disease Control and Prevention (CDC) disease class, CDC immunologic class, serum immunoglobulin (Ig) levels, or in the use of antiretroviral therapy. However, responders tended to have higher age-adjusted absolute CD4 cell counts than nonresponders (p = 0.07). Nonetheless, there was no correlation between antibody levels and age-adjusted CD4 counts for each of the 4 TCD vaccines. Responders had conserved lymphoproliferative responses to mitogens and to candida antigen; 7 (41%) had normal responses to tetanus antigen. While nonresponders had some conserved responses to mitogens, only 1 had a response to antigen. Thirteen responders (77%) and only 1 nonresponder (20%) had normal responses to at least 2 of the 3 mitogens and 1 of the 2 antigens (p = 0.04). Although defects in B-cell differentiation were detected in both groups, they were profound and generalized in the nonresponders. Fourteen responders (82%) had at least 1 normal B-cell response compared with none of the 5 nonresponders (p = 0.002). There were no correlations between normal lymphoproliferative responses and age, CD4 counts, serum immunoglobulin G (IgG) levels, or the use of antiretroviral therapy. Immunologic function is important in the evaluation of HIV-infected children.

Growth failure as the first expression of malnutrition in children with human immunodeficiency virus infection.

BACKGROUND: To define the onset, pattern, and earliest manifestations of malnutrition related to HIV infection. METHODS: A retrospective cross-sectional analysis of changes in weight and growth in a group of 54 children with perinatally acquired HIV infection was conducted. Eight children had asymptomatic HIV infection, 26 had symptomatic infection, and 20 had symptomatic infection and were referred for nutritional support. RESULTS: We found an early decline in the rate of linear growth with a relative preservation of the weight-for-age. Weight-for-height measurements were preserved until there was advanced HIV-related disease. CONCLUSIONS: This pattern can result in a false impression of adequate nutrition and emphasizes the importance of longitudinal growth data of the child with HIV infection. Evidence of linear growth failure before clinical wasting is apparent is an absolute indication for aggressive nutritional support.

Immunity to Haemophilus influenzae type b polysaccharide capsule in children with human immunodeficiency virus infection immunized with a single dose of Haemophilus vaccine.

We studied immunity to Haemophilus influenzae type b (Hib) polysaccharide capsule in 19 children infected with human immunodeficiency virus (HIV) immunized with a single dose of a Hib vaccine at a mean age of 28 months (range, 15 to 56 months). Four to eighty-five months after immunization, only 7 children (37%) were immune. There were no significant differences in the HIV classification of the Centers for Disease Control and Prevention, type of conjugate vaccine, age at vaccination or serologic testing, time from vaccination to antibody determination, and CD4 cell counts between children with and those without immunity.

Antibodies to lipooligosaccharide of a Brazilian purpuric fever isolate of Haemophilus influenzae biogroup aegyptius lack bactericidal and protective activity.

The immunological basis for protection against Brazilian purpuric fever (BPF), a fulminant infection of young children associated with bacteremia with Haemophilus influenzae biogroup aegyptius, is unknown. Candidate antigens to which protective antibodies may be directed include cell surface proteins and lipooligosaccharide (LOS). We studied the activity of antisera to LOS purified from a BPF H. influenzae biogroup aegyptius isolate. Anti-LOS antisera contained anti-LOS antibody by enzyme immunoassay and immunoblot and no detectable anti-outer membrane protein antibodies by immunoblot. Anti-LOS antisera had minimal bactericidal activity and were not protective against the homologous strain in an infant rat model of bacteremia. Antiserum to whole bacterial cells had a titer of anti-LOS antibody similar to that of anti-LOS antisera and was bactericidal and protective. Removal of anti-LOS antibodies from anti-whole cell antiserum by affinity chromatography did not result in a loss of bactericidal activity. Serum from a normal adult contained anti-LOS antibodies and had bactericidal activity. However, anti-LOS antibodies purified from this serum did not have detectable bactericidal activity. These studies suggest that anti-LOS antibodies produced in rats are not bactericidal and do not contribute to protection against experimental bacteremia with BPF strains of H. influenzae biogroup aegyptius.

Immunity to Haemophilus influenzae type b polysaccharide capsule after vaccination with the complete series of oligosaccharide CRM197 conjugate vaccine in infants with human immunodeficiency virus infection.

We evaluated immunity to Haemophilus influenzae type b (Hib) in 18 human immunodeficiency virus-infected infants who were vaccinated with a complete series of Hib conjugate vaccine. Four months after the primary series, the geometric mean anticapsular antibody concentration in 11 children was 0.40 microgram/ml. There were no significant differences in CD4+ cell counts or in the Centers for Disease Control and Prevention disease classification according to the presence of immunity to Hib. Four months after the booster dose, the geometric mean anticapsular antibody concentration in the 18 children was 0.82 microgram/ml. Children with immunity were more likely than children lacking immunity to have higher CD4+ cell counts and mild human immunodeficiency virus-related disease. The majority of the anticapsular antibody concentrations were lower than in healthy children.

Oropharyngeal candidiasis in immunocompromised children: a randomized, multicenter study of orally administered fluconazole suspension versus nystatin. The Multicenter Fluconazole Study Group.

OBJECTIVE: To compare the efficacy, safety, and tolerance of fluconazole suspension versus nystatin in the treatment of oropharyngeal thrush in immunocompromised children. DESIGN: Multicenter, randomized, observer-masked trial. SETTING: Thirty-two centers participated, including hospitals and ambulatory care clinics. PATIENTS: We enrolled 182 immunocompromised infants and children, ages 5 months to 14 years, with signs of oral thrush and presence of yeasts on potassium hydroxide- or gram-stained preparations. Subjects were randomly assigned to receive a single daily dose of fluconazole suspension, 2 to 3 mg/kg per day, or nystatin, 400,000 units four times daily for 14 days; 159 patients, who had culture confirmation of thrush and received at least 7 days of study drug, were evaluated for efficacy; all patients were evaluated for safety. RESULTS: Clinical cure was demonstrated in 91% of the subjects in the fluconazole group and 51% of the subjects in the nystatin group (p < 0.001), and eradication of the organism cultured at entry occurred in 76% and 11% (p < 0.001), respectively. Gastrointestinal conditions developed in six patients who received fluconazole and in three who received nystatin; two fluconazole recipients were subsequently withdrawn from the study. Laboratory abnormalities occurred with equal frequency in both groups. Clinical relapse rates were similar in both groups at 2 weeks (18% and 24% for fluconazole and nystatin, respectively) and 1 month (28% and 27%, respectively) after the completion of study drug. CONCLUSIONS: Fluconazole suspension is more effective than nystatin in the treatment of thrush in immunocompromised children. Both regimens were well tolerated.