Mesenteric lymph nodes of the rat were studied by scanning electron microscopy after arterial perfusion fixation. Observation was made mainly of the high endothelial venules (HEVs), inner cortex and medulla. The HEVs were distributed not only in the inner cortex, but also in the interfollicular areas in the outer cortex, extending to closely beneath the marginal sinus. Various surface structures of the HEV endothelial cells were recorded, from quite smooth to densely granular. Special attention was paid to endothelial cells with cytoplasmic ridges concentrated at the center of the cell apex. Lymphocytes were numerously attached to the luminal surface of the HEV. Many lymphocytes presumably under and after emigration through the HEV wall could be recognized. Hitherto unknown labyrinths densely filled with lymphocytes were demonstrated in the inner cortex. These tubular and saccular spaces lined by attenuated cells originated from beneath the germinal centers and from around the HEVs to pour into the medullary sinuses. The lymphatic labyrinths were differentiated from the sinuses by their lack of reticular cell trabeculae and by their containing almost exclusively small lymphocytes. It was proposed that lymphocytes in the blood in HEVs massively emigrate to the labyrinth, and via the medullary sinuses, enter the efferent lymphatics of the lymph node. In the medullary sinuses, some lymphocytes in association with a macrophage were found to extend wing-like processes, probably reflecting their activation. Large free cells extending laminar projections, but smooth in surface otherwise, were occasionally found. Their possible identity with the veiled cells (KELLY et al., 1978) was considered.

Animals↗

PubMedDate not supplied

The effectiveness of interventions on incubation of AIDS as measured by secular increases within a population.

Methods are developed to estimate and test for the impact of intervention use on a population's survival function (time to AIDS). Each participant's history is divided into J + 1 components: omega 0 occurring before the intervention is available and omega 1 to omega J occurring later, as the intervention becomes successively more available. Distribution free truncated Kaplan-Meier models based on time since exposure fit separately to the risk sets/outcomes in omega 0 to omega J directly show the changing patterns of survival. Multivariate proportional hazards models can be used to adjust for covariates. Application of these methods indicates that availability of proven anti-AIDS interventions may have delayed time to AIDS by 8 months in an educated HIV-1 infected homosexual cohort with good access to medical care.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

A cross-national EEG study of children with emotional and behavioral problems: a WHO collaborative study in the Western Pacific Region.

Electroencephalograms (EEGs) of children from the general population, assessed by Rutter's questionnaires as having deviant behavior, were quantitatively evaluated in Japan (n = 27), China (n = 39), and Korea (n = 87). Compared with age-matched normal behavior children in Japan (n = 30), China (n = 27), and Korea (n = 26), there were no differences either in the EEG frequency pattern or other EEG variables. The EEGs of age-matched children diagnosed with attention deficit disorder with hyperactivity in psychiatric clinics in Japan (n = 21), China (n = 41), and Korea (n = 29), were significantly different from those of normal and deviant behavior groups. There were more delta and fast theta waves and fewer alpha waves in all three countries, and hypothetical EEG maturation was retarded in Japan and China. These results suggest that the deviant behavior of children in the general population had no biological background, but presumably stemmed from psychosocial disadvantages. In contrast, the symptoms of hyperactive children seemed to be related to a biological dysfunction such as brain immaturity.

Attention Deficit Disorder with Hyperactivity↗

PubMedDate not supplied

Beta A4 deposits are constant in the brain of the oldest old: an immunocytochemical study of 20 French centenarians.

beta A4 deposits occur in the brain of some individuals over 50 years of age. It could be a part of the aging process or indicate a disease found frequently in the elderly. To address this question, beta A4 immunocytochemistry was performed on the brain of 15 nondemented and 5 demented centenarians, some of whom were affected by Alzheimer's disease. We found beta A4 deposits in the parahippocampal and the superior temporal gyri of all the cases, whatever the clinical state. The hippocampus was frequently spared. The lesion density was not correlated with the severity of the mental deterioration. The constant deposition of beta A4 protein in the brain of very old people indicates that this process does not spare a large proportion of this population. This result favors beta A4 accumulation in the brain being an ineluctable age-related process.

Aged↗

PubMedDate not supplied

Beta AP deposition and head trauma.

Head trauma is considered to be a risk factor for Alzheimer's disease, because a high prevalence of beta AP deposits has repeatedly been reported in patients who died within a few days following head injury. To evaluate this statement, we undertook two studies using immunohistochemistry for beta AP and found a surprisingly low prevalence of beta AP diffuse deposits. We first selected 23 patients aged 17-63 years, who died 0-76 days after head trauma. Using beta AP antibody at the usual dilution (1:100), we did not find any deposits. With a high concentration of antibody (dilution 1:2) we found beta AP diffuse deposits in one 46-year-old case. In a second study, 17 patients aged 60-79 years old, who died 1-35 days after head injury, were compared to a control group. We did not find any significant difference in the density of beta AP diffuse deposits between cases and controls using usual dilutions of beta AP antibody. The density of beta AP diffuse deposits was linked only to aging and the presence of senile plaques.

Adolescent↗

PubMedDate not supplied

Diagnosis of schistosomiasis japonica in Chinese schoolchildren by administration of a questionnaire.

This paper describes a rapid, simple, cost-effective questionnaire for screening school-aged children at risk for Asian schistosomiasis in China. Five hundred and thirty-two children, aged 8-14 years, were selected from 3 schools in an area moderately endemic for Schistosoma japonicum in Hunan province. The questionnaire, comprising 15 multiple-choice questions, was administered by teachers in order to collect both ethnographic and epidemiological data relevant to current S. japonicum infections. This was followed by Kato-Katz thick smear stool examinations, miracidium hatching tests, and soluble egg antigen-enzyme linked immunosorbent assays in order to validate the efficacy of the questionnaire approach. The results from a combination of all 3 procedures indicated that the overall schistosomiasis prevalence in the 3 schools was 29.9% (138/472). Six risk factors (episodes of diarrhoea, frequency of water contact, school grade attained, weakness, past history of S. japonicum infection(s), and whether a subject had been previously treated for schistosomiasis) in the questionnaire were determined by logistic regression to be highly statistically significant predictors of individual current infection. The sensitivity (93.7%), specificity (91.9%) and low cost (c. US$ 0.6/true positive case) associated with the 6 variables model make the questionnaire approach a very useful diagnostic tool for screening marshland and lake communities at high risk for schistosomiasis in China before selective treatment with praziquantel or diagnostic follow-up. An even simpler 3 variables 'yes/no' model was derived from the questionnaire and found to be nearly as good at predicting individual infection (sensitivity 86.2% and specificity exceeding 97.6%) and extremely simple to use. If validated in other ecological settings in China the questionnaire, modified or as presented here, could be adopted by the national schistosomiasis control programme.

Adolescent↗

PubMedDate not supplied

Modeling the relation between neurofibrillary tangles and intellectual status.

The relationship between the neurofibrillary tangles and the intellectual deficit observed in senile dementia of the Alzheimer type was studied in 27 patients over the age of 75. The presence and density of tau positive tangles were assessed in six areas including limbic, paralimbic, and isocortical cortices. In the isocortical areas, the presence [1] or absence [0] of neurofibrillary tangles was better correlated with the Blessed test score than the density of the neurofibrillary tangles profiles. Multivariate analysis showed that the number of areas containing at least one neurofibrillary tangle was the best explanatory variable of the intellectual status. The cortical areas were ranked according to the prevalence of their involvement. The presence of tangles in an area of a given rank took place only if the areas of lower ranks were also involved. It is proposed that the presence of tangles in a given area is a more significant information than the value of their density. These data may lead to new diagnostic procedures.

Aged↗

PubMedDate not supplied

Microarray-based compendium of hepatic gene expression profiles for prototypical ADME gene-inducing compounds in rats and mice in vivo.

To examine species-specific aspects of the induction of absorption, distribution, metabolism and excretion (ADME)-related genes, we used 25 000 gene oligonucleotide microarrays to construct a rodent gene-response compendium that compared hepatic gene expression profiles and developed consensus aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR) and pregnane X-receptor (PXR) ligand signatures relevant to drug clearance. Twenty-six inducer compounds were chosen from the literature. Rats and mice received one of six dose levels (log2 dose escalation, 32-fold dose range) of each compound daily for 3 days. Animals were necropsied 6-9 h after the last dose, and tissues were collected for RNA analysis. Hepatic gene expression profiles were obtained using Rosetta Resolver expression analysis system, and ADME-related genes were extracted. Cross-talk among nuclear receptors or hepatoxicity at high dose levels resulted in large signatures (usually >1000 genes at p < 0.01) for most compounds. After ADME gene transcript enrichment, agglomerative clustering separated AhR ligands from CAR/PXR ligands, but it was difficult to distinguish CAR from PXR ligands. Consensus signatures were derived from groups of AhR, CAR and PXR ligands; and cross-talk among responding genes was determined. Many compounds had distinct log dose-response profiles, and relative potencies for ligands were established. Robust responses by CYP1A1, CYP2B10 (CAR responsive in mice) and CYP2B15 (CAR responsive in rats) and CYP3A1 (PXR responsive in rats) were used to benchmark the relative potency of different ligands and to determine the relative selectivity for AhR, CAR or PXR. By using a compendium of gene expression profiles, we defined species-specific induction patterns across the ADME transcriptome.

Animals↗

PubMedDate not supplied

Compendium of gene expression profiles comprising a baseline model of the human liver drug metabolism transcriptome.

Oligonucleotide microarrays were used to study the variability of pharmacokinetics and drug metabolism (PKDM)-related gene expression in 75 normal human livers. The objective was to define and use absorption, distribution, metabolism and excretion (ADME) gene expression variability to discern co-regulated genes and potential surrogate biomarkers of inducible gene expression. RNA was prepared from donor tissue and hybridized on Agilent microarrays against an RNA mass balanced pool from all donors. Clustering of PKDM gene sets revealed donors with distinct patterns of gene expression that grouped genes known to be regulated by the nuclear receptor, pregnane X-receptor (PXR). Fold range metrics and frequency distributions from the heterogeneous human population were used to define the variability of individual PKDM genes in the 75 human livers and were placed in context by comparing expression data with basal ADME gene expression variability in an inbred and diet/environment controlled population of 27 Rhesus livers. The most variable genes in the hepatic transcriptome were mainly related to drug metabolism, intermediary metabolism, inflammation and cell cycle control. Unique patterns of expression across 75 individuals of inducible ADME gene expression allowed their expression to be correlated with the expression of many other genes. Correlated genes for AhR, CAR and PXR responsive genes (CYP1A2, CYP2B6 and CYP3A4) were identified that may be co-regulated and, therefore, provide clues to the identity of surrogate gene or protein markers for CYP induction. In conclusion, microarrays were used to define the variable expression of hepatic ADME genes in a diverse human population, the expression variability of ADME genes was compared with the expression variability in an inbred population of Rhesus monkeys, and genes were defined that may be co-regulated with important inducible CYP genes.

Animals↗