Plasma virus load evaluation in relation to disease progression in HIV-infected children

The purpose of the study was to investigate if the presence of vertical destruction in proximal sites influences periodontal status and healing in adjacent sites in the same proximal space without vertical destruction. The investigation was conducted as a retrospective study on a 3-year consecutive referral population of periodontitis-prone patients based on full-mouth oral radiographic examinations, probing pocket depth registrations and plaque scores. The analyses were performed by using regression analyses on a final sample of 1169 (periodontal status) and 1051 (periodontal healing) proximal sites in 163 patients. The relative radiographic attachment level (RRAL) in proximal horizontal sites did not depend on the type of destruction, vertical or horizontal, in the adjacent proximal sites. However, after non-surgical treatment, pocket-depth reduction in proximal sites with horizontal destruction was significantly reduced in the presence of a vertical destruction in the adjacent proximal site compared to the corresponding sites adjacent to a horizontal defect. It was concluded that marginal periodontal healing in proximal sites with horizontal destruction is impaired by the presence of a vertical destruction in the adjacent proximal site.     

Neurobehaviour of school age children born to diabetic mothers

AIM: To study the neurobehavioural effects that diabetes during pregnancy might have on children by school age. METHODS: The neurobehavioural function of 57 school age children born to 48, well controlled diabetic mothers was compared with 57 control children matched for age, birth order, and parental socioeconomic status, using several cognitive, behavioural, sensory and motor neurological tests. RESULTS: The IQ scores of the index group children were similar to those of control children (117.7 +/- 13.4 vs 118.5 +/- 10.1). There were no differences between the groups in various sensory motor functions. However, the index group children performed less well than the controls on indices of fine and gross motor functions, as observed on the Bruininks-Oseretzky test of motor proficiency. The scores of children born to diabetic mothers were higher than controls on the Touwen and Prechtl neurological examination. They also performed worse in the Pollack tapper test which is designed to detect minor neurological deficits, inattention, and hyperactivity. The index children had higher scores on the Conners abbreviated parent-teacher questionnaire which measures hyperactivity and inattention. There was a negative correlation between the performance of the index group children on various neurodevelopmental and behavioural tests and the severity of hyperglycaemia, as assessed by blood glycosylated haemoglobin and acetonuria. CONCLUSIONS: Diabetes during pregnancy adversely affects some fine neurological functions in children at school age, but not their cognitive scores. These effects are not correlated with the degree of glycaemic control.     

Virus load as a marker of disease progression in HIV-infected children

The relationship of virus load to clinical disease progression in HIV-infected children remains to be elucidated. In this study, HIV-1 proviral DNA load was determined in peripheral blood mononuclear cells (PBMCs) by the quantitative competitive DNA polymerase chain reaction assay (QC-PCR) in 47 HIV-infected children subdivided by age (group I, < or = 2 years; group II, > or = 5 years), who were further categorized to include 12 rapid progressors (RP, age < or = 2 years, Centers for Disease Control [CDC] defined clinical category C and/or immune category 3, or death before age 2 years) and slow progressors (SP, age > or = 5 years, excluding CDC categories C and/or immune category 3). Significantly higher mean proviral copies/10(3) PBMCs were detected in group I versus group II (75.4 +/- 104.3 and 13.0 +/- 17.8 respectively, p < 0.0001) and in RP (158.0 +/- 118.2) as compared to either SP (11.8 +/- 18.8, p < 0.0001) or other age-matched infected children (20.3 +/- 38.8, p < 0.0001). Thus HIV-infected children appear to have a higher cell-associated virus load early in life, especially in association with rapid disease progression.     

Oligoclonal expansion of HIV-specific cytotoxic CD8 T lymphocytes in the skin of HIV-1-infected patients with cutaneous pseudolymphoma

A massive infiltration of the skin by activated CD8+ T lymphocytes involving both the dermis and the epidermis has been found in HIV-1-infected patients presenting with a chronic skin rash. We characterized the T cell receptor (TCR) BV-BJ junctional diversity of the skin-infiltrating lymphocytes (SILs) in four patients. The SILs expressed a limited set of TCRBV gene segments. Complementarity determining region 3 length analysis further emphasized their oligoclonality, suggesting that antigen stimulation might be responsible for the cutaneous T cell expansion. Furthermore, independent skin biopsies obtained from the same individual were shown to harbor distinct T cell repertoires, possibly reflecting the spatial heterogeneity of the antigenic stimuli. The CD8+ cytotoxic T lymphocyte (CTL) lines isolated from the skin rash in one patient exhibited a specific, class I MHC-restricted cytotoxic activity against HIV-1 Gag- and Pol-expressing target cells, whereas CTL lines derived from the skin lesions of a second patient were shown to be predominantly Env-specific. Taken together, these data demonstrate the infiltration of HIV-specific CTLs in the skin of HIV-infected patients, and suggest that in addition to their known role in controlling the retroviral infection, these CTLs may also be involved in the pathogenesis of cutaneous inflammatory disorders occurring during the course of HIV infection.     

T-cell receptor V beta-specific expansions in children from HIV-infected mothers

This paper present a tonometer incorporated in a contact lens, which allows simultaneous measurement of intraocular pressure and performance ophthalmoscopy. The tonometer can record the pulse curve continuously, which can give us an indication of any circulatory problem. The device is therefore expected to yield additional information useful for the diagnosis of early glaucoma. Te device has three force sensors built in, which allow continuous measurement of the force exerted on the eye surface by the contact lens. The force of the contact lens on the eye can be altered and makes the adjustment of different eye pressures possible. These induced changes of the eye pressure and their influence on the fundus can be checked. We have taken some measurements on enucleated human eyes to compare our device with a Statham tansducer in the vitreous. We found a good correlation. We are currently taking measurements in volunteers. The clinical relevance of these observations and measurements will be examined in a future study.     

Longitudinal assessment of growth in children born to mothers with human immunodeficiency virus infection

OBJECTIVES: To describe and to evaluate the longitudinal growth of children born to mothers with human immunodeficiency virus (HIV) infection. DESIGN: Measurements of weight, length (measured in infants in a recumbent position) and height (measured in older children in an upright position), and head circumference were documented and evaluated longitudinally using generalized estimating equations in a group of children born to HIV-infected mothers. Children infected with HIV were compared with uninfected children and with National Center for Health Statistics standards. SETTING: Primary care clinic in an urban hospital devoted to the medical care of children born to HIV-infected mothers. PATIENTS: One hundred nine children born to HIV-infected mothers, 59 HIV-infected and 50 uninfected, between birth and 70 months of age. RESULTS: The mean birth weights of both groups were below the 50th percentile. While the mean weight-for-age curve of uninfected children attained the 50th percentile by age 24 months, the mean birth weight-for-age curve of HIV-infected children remained below the 50th percentile. Weight gain became significantly different between the two groups by age 36 months. The mean birth length-for-age curves of HIV-infected and uninfected children was also below the 50th percentile. The mean height-for-age curve of uninfected children attained the 50th percentile by age 40 months, while that of HIV-infected children remained well below the 50th percentile. Linear growth between HIV-infected and uninfected children diverged earlier than weight, becoming significantly different by age 15 months. CONCLUSIONS: Although children born to HIV-infected mothers are born with weight and length below the 50th percentile, uninfected children catch up, while HIV-infected children remain below the 50th percentile and experience an earlier and more pronounced decrease in linear growth (height-for-age) than in weight-for-age.     

Immunological characteristics of HIV-infected children: relationship to age, CD4 counts, disease progression, and survival

We have evaluated immunologic markers of disease progression in 79 children perinatally infected with HIV. Laboratory testing included T lymphocyte subsets and lymphoproliferative responses (LPR) to mitogens (PHA, Con A, and PWM), antigens (Candida, Tetanus), and alloantigens (MLC). Patients were graded into grades I, II, and III based on results of CD4 counts, and into grades A, B, and C based on results of LPR, with grades I and grades A being normal, III and C being the lowest, and II and B falling in-between. CD4 counts, CD4/CD8 ratio, and lymphoproliferative responses were markedly decreased in a majority of children. Grade III CD4 counts were almost always associated with decreased LPR. A majority of the children with grade I CD4 numbers, however, also had abnormal lymphoproliferative responses. Results of laboratory testing were analyzed in relation to clinical disease progression and survival. The first AIDS defining illnesses (ADI), especially opportunistic infections (OI), was usually associated with Grade III/C results in immunologic assays. Survival was significantly decreased in children with grade III CD4 cell counts, and grade C LPR, and was poorest if these abnormalities developed within the first year of life. In this latter age group, if the CD4 counts fell to grade III, the risk for dying was at least five times greater than those children with higher CD4 counts (grades II and I); if the proliferative responses to PHA and MLC were in Grade C, the survival was 22 months. Severe immune defects in the first year of life in children with HIV infection, as assessed by CD4 counts and a battery of functional tests, predicted rapid disease progression.     

Routine vaccination and vaccine-preventable infections in children born to human immunodeficiency virus-infected mothers. European Collaborative Study

Information on vaccinations and vaccine-preventable infections collected in a prospective study of children born to human immunodeficiency virus (HIV)-infected mothers was analysed for reports of adverse reactions and to estimate the clinical efficacy of vaccines. No vaccinated, HIV-infected child developed measles (56 child-years' follow-up), mumps (33), rubella (33) or pertussis (239), and only one adverse reaction - to Bacillus Calmette-Guerin (BCG) - was reported. These findings provide limited evidence of the safety and efficacy of routine vaccination of HIV-infected children.     

Mature maternity: long term associations in first children born to older mothers in 1970 in the UK

We discuss the well-known problems associated with efforts to detect and characterize chaos and other low dimensional dynamics in biological settings. We propose a new method which shows promise for addressing these problems, and we demonstrate its effectiveness in an experiment with the crayfish sensory system. Recordings of action potentials in this system are the data. We begin with a pair of assumptions; that the times of firings of neural action potentials are largely determined by high dimensional random processes or "noise"; and that most biological files are non stationary, so that only relatively short files can be obtained under approximately constant conditions. The method is thus statistical in nature. It is designed to recognize individual "events" in the form of particular sequences of time intervals between action potentials which are the signatures of certain well defined dynamical behaviors. We show that chaos can be distinguished from limit cycles, even when the dynamics is heavily contaminated with noise. Extracellular recordings from the crayfish caudal photoreceptor, obtained while hydrodynamically stimulating the array of hair receptors on the tailfan, are used to illustrate the method.     

Tumors with reduced expression of a cytotoxic T lymphocyte recognized antigen lack immunogenicity but retain sensitivity to lysis by cytotoxic T lymphocytes

A murine solid tumor was transfected to express various levels of an allogeneic major histocompatibility complex class I gene (K216), in order to test the effect of the level of antigen expression on immunogenicity and sensitivity to lysis by cytotoxic T lymphocytes (CTL). The growth rates of clones of tumor cells expressing different levels of the transfected gene were similar in vitro and in nude mice. Although all tumor cells, including cells freshly isolated from growing tumors, were equally sensitive to lysis by specific CTL, only tumor cells expressing the highest level of the K216 antigen stimulated CTL and were rejected by normal mice. In contrast, tumor cells expressing lower levels of antigen failed to immunize for CTL and grew progressively in normal mice, despite retaining expression of the transfected gene and remaining fully sensitive to CTL-mediated lysis; thus, the threshold of antigen needed to stimulate CTL responses was considerably higher than that needed to lyse tumor cells. Reduction of K216 antigen expression from 100-fold to 40-fold above background, impaired significantly the ability of the tumor cells to induce a K216-specific immune response, while tumor cells expressing K216 at levels 2-fold above background were as susceptible to CTL-mediated lysis as tumor cells expressing 50-fold more antigen. The important implication of these findings is that some tumors occurring in nature may not be immunogenic but nevertheless express antigens which are potential targets for immune therapy.     

Cognate peptide-induced destruction of CD8+ cytotoxic T lymphocytes is due to fratricide

In the absence of other cells, cloned CTL in culture can undergo massive destruction upon the addition of a peptide that is recognized, in association with the CTL's class I MHC proteins, by the CTL's Ag-specific TCR. To determine whether the destruction is a result of the individual CTL's recognition via its own TCR of peptide-MHC-I complexes on its own surface ("suicide"), or to cytolytic attack by some CTL on others in the same culture ("fratricide"), we compared the rate of peptide-induced cell death in conventional cultures, where CTL are free to establish cell-cell contacts, with other cultures in which individual CTL were prevented from forming cell-cell contacts by encasing them individually in agarose gel microdrops. The differences were dramatic: in the presence of high concentrations of peptide (10 millionfold greater than is necessary to support 50% lysis of conventional target cells by these CTL) cell death was linear over 0 to 8 h in conventional cultures, at a rate of about 10% per hour, whereas in the presence of the same high concentration of peptide over the same time course, no death was detected among the cells encased in agarose gel microdroplets. The results demonstrate an absolute requirement for cell-cell contact in the destruction of cloned CTL in culture with their cognate peptides at high concentration. Using an increase of intracellular calcium ion concentration ([Ca2+]i) as a measure of T-cell activation, we also found that peptide-dependent activation of CTL likewise depends upon cell-cell contact.     

Developmental and food profiles of infants born to adolescent and adult mothers

OBJECTIVE: To compare developmental markers and dietary intake of infants born to lower socioeconomic adolescent and adult mothers. DESIGN: Sixty-one adolescent (age 14-18 years) and 60 adult (age 22-28 years) mothers met inclusion criteria of comparable socioeconomic status, age range, urban/rural residence, and distribution of infants by gender. SAMPLE/SETTING: Adolescent subjects were recruited in last trimester and adult mothers postpartum. Interviews were conducted when infants were about 6 and 12 months of age. Data included age of occurrence for eight markers, age at adding complementary foods, two 24-h dietary recalls, and two measurements of growth. RESULTS: Adolescent mothers reported a significantly earlier age at which the infant "holds a spoon by self" and "drinks alone from a trainer cup." Six other markers were not significantly different between groups. Adolescent mothers fed cereal significantly earlier than did adult mothers, but there were no significant differences for fruit, vegetables, and meat. At 12 months, infants of adolescents had intakes of vitamin D and iron which were < 100% of recommended allowances, as did infants of adult mothers for vitamin D, iron, and zinc. Dietary fat was significantly higher at 6 and 12 months and vitamin C was lower at 12 months for infants of adolescents compared to the adult group. CONCLUSIONS: Compared to adult mothers, adolescent mothers reported earlier mean ages for developmental markers related to self-feeding, and introduced cereal earlier. In each group, selected nutrient intakes decreased from recommended amounts in the 6-12-month period. Fat intakes were significantly different between groups at 6 and 12 months.     

HLA-A*0201 presents TAP-dependent peptide epitopes to cytotoxic T lymphocytes in the absence of tapasin

Tapasin is a 48-kDa endoplasmic reticulum (ER)-resident glycoprotein that binds to the transporter associated with antigen processing (TAP) and mediates an interaction between TAP and newly synthesized MHC class I molecules. It is also essential for the proper antigen presenting function of HLA-A*0101 (HLA-A1), HLA-A*0801 (HLA-B8) and HLA-B*4402 (HLA-B4402). We show here that while tapasin is required for HLA-A*0201 (HLA-A2) molecules to bind to TAP, its absence does not block the presentation of HLA-A2-restricted TAP-dependent epitopes to cytotoxic T lymphocytes indicating that, unlike HLA-A1, HLA-B8 and HLA-B4402, HLA-A2 has access to the TAP-dependent peptide pool even in the absence of tapasin. Nevertheless, the overall efficiency with which HLA-A2 was loaded with optimal, stabilizing peptides was impaired in the cell line .220, resulting in a significant increase in the fraction of HLA-A2 molecules being released from the ER in a "peptide-receptive" state.     

Absence of infection in breast-fed infants born to hepatitis C virus-infected mothers

The role of breast-feeding in perinatal transmission of hepatitis C virus (HCV) was explored in 15 HCV-infected mothers and their infants. The 15 carrier mothers had anti-HCV titers ranging from 1:80 to 1:40,000 and also had HCV-ribonucleic acid with concentrations ranging from 10(4) to 2.5 x 10(8) copies/ml. Both anti-HCV antibody and HCV-ribonucleic acid were present in colostral samples in much lower levels, but none of the 11 breast-fed infants had evidence of HCV infection for up to 1 year of age. Thus breast-feeding seems safe for these infants.     

Involvement of both donor cytotoxic T lymphocytes and host NK1.1+ T cells in the thymic atrophy of mice suffering from acute graft-versus-host disease

The control and eventual eradication of H5N2 influenza virus from domestic poultry in Mexico is dependent on the use of avian influenza (AI) vaccine strategies. This study was performed to determine the amount of hemagglutinin (HA) antigen required to control the signs of disease from a highly pathogenic H5N2 influenza virus (A/Chicken/ Queretaro/19/95) and the amount of antigen required to prevent shedding of virus from vaccinated birds. Six commercial inactivated water in oil H5N2 vaccines available in Mexico were compared with standardized vaccines to assess their efficacy. The amount of HA required to prevent the signs of disease from A/Chicken/Queretaro/19/95 influenza virus was approximately 0.4 microgram per dose. Each of the six commercially available vaccines prevented disease signs, and half of the vaccines significantly reduced viral shedding from vaccinated birds. There is a need for standardization of AI virus vaccine, and the antigen content should be increased in some of the commercially available AI vaccines in Mexico.     

HIV-1-specific cytotoxic T lymphocytes and the control of HIV-1 replication

The present study examined the effect of perceived problem-solving ability (self-identified effective and ineffective) operationalized by Heppner and Petersen's Problem Solving Inventory (PSI) and random feedback (success vs. failure) on participants' attributions. A total of 30 female and 30 male teacher trainees who had scored in the top and bottom distribution of the PSI dealt with three unexpected classroom disruptions during a lecture presentation. After their presentation, they received randomized feedback concerning their performance during disruptions. Following feedback, they completed Baumgardner's Attribution Questionnaire (AQ). Results indicated a significant PSI x Feedback interaction for ability and effort but not for task difficulty and luck. Perceived efficacious problem solvers' internal attributions depended on whether they received success or failure feedback. Similar to the self-enhancing tendency reported in the literature, this group attributed success versus failure more to ability and effort. The perceived ineffective problem solvers' attributions did not differ based on the feedback they received. Results are discussed in terms of prior research and theory.