Hepatic microvascular development in relation to the morphogenesis of hepatocellular plates in neonatal rats

The development of hepatic microvascular heterogeneity after birth, and its temporal relationship to the development of parenchymal cell plates have received little attention. As a result, the morphogenesis of some of the parameters contributing to this heterogeneity in suckling and weaned rats was studied as a function of time between postpartum days 4 and 30 using in vivo light microscopic, electron microscopic, and immunocytochemical methods. During the early suckling period, the sinusoid network is highly anastomotic, with little evidence of zonation, and the parenchymal cell plates contain multiple cells and are irregularly arranged throughout the lobule. Sinusoidal endothelial fenestration is sparse at 4 days, but phagocytic Kupffer cell (KC) function already exists and exhibits zonal heterogeneity, with more cells located in the periportal zone. With increasing age, endothelial fenestrae increase and organize as sieve plates. Widened centrilobular radial sinusoids form through a loss ("drop-out") of intersinusoidal sinusoids (ISS). Concomitantly, the associated cell plates straighten and become one cell thick. Hepatocyte DNA synthesis and mitosis are higher in the periportal zone, which retains thickened cell plates and anastomotic sinusoids. The centrilobular sinusoids may widen to accommodate the increased volume of blood that results from the loss of ISS as well as the increased numbers of periportal sinusoids containing flow that feed these vessels. KC phagocytic activity increases during the suckling period concomitant with an increase of gut-derived endotoxin in the portal blood, which suggests that the KCs may be releasing mediators that affect sinusoid diameter, blood flow, endothelial fenestration, and perhaps parenchymal growth either directly or through the stimulation of growth factors.     

Validation of an equation for predicting energy cost of arm ergometry in women

Few studies have examined the validity of metabolic equations for the prediction of energy cost (VO(2)) of arm ergometry in women. Therefore, the purpose of this study was (a) to compare directly measured and predicted VO(2) values using the American College of Sports Medicine (ACSM) equation and (b) to develop and validate a prediction equation for women. A sample of 60 female subjects with mean (+/-SD) age, weight and height 26.5 +/- 14.4 years, 61.5 +/- 7.6 kg, 163.3 +/- 6.0 cm, respectively, was randomly assigned to an equation group (N = 40) and a cross validation group (N = 20). All subjects performed an incremental arm ergometry test (10 W increases every 2 min), until termination criteria were met. Repeated measures ANOVA indicated significant differences between the measured VO(2) and ACSM predicted VO(2) during all the incremental test work rate. Multiple linear regression analysis was used to develop the following upper body exercise VO(2) prediction equation: VO(2)(ml . kg(-1) . min(-1) = 23.461 - (0.272 x Body Weight) + (0.403 x watts) [R(2) = 0.82, SEE = 2.79] Cross validation indicated lower variability using the current prediction equation. An additional independent sample of 13 subjects performed a 30-min steady-state test at 40% of their pre-determined maximal work rate. VO(2) measured during the 30 min steady-state test (was significantly different P < 0.05) from the ACSM prediction at all time intervals. There were no significant differences using the above equation following the 5 min time interval. Therefore, a new equation is proposed as a means of providing a gender-specific energy cost prediction equation.     

TH1 and TH2 cytokine mRNA and protein levels in human immunodeficiency virus (HIV)-seropositive and HIV-seronegative youths

The roles of cytokines in the progression of human immunodeficiency virus (HIV)-associated disease are controversial. The patterns of innate cytokine production have been postulated to shift from TH1- to TH2-type cytokines with the progression of HIV-associated disease. Although there have been studies of cytokines in children and adults, no data are available on cytokine production in healthy or HIV-infected adolescents. We analyzed and characterized cytokine mRNA and protein levels for gamma interferon, interleukin 2 (IL-2), IL-4, and tumor necrosis factor alpha and protein levels of IL-6 in both stimulated and unstimulated peripheral blood mononuclear cells obtained from a large longitudinal, observational cohort study of HIV-seropositive and -seronegative adolescents. We correlated cytokine results with viral load and CD4(+)-T-cell counts as critical markers of disease progression in HIV-infected adolescents. These data were used to examine hypotheses related to the TH1-to-TH2 cytokine shift in a sample of HIV-infected adolescents. Five hundred twenty subjects participating in the REACH (Reaching for Excellence in Adolescent Care and Health) Project of the Adolescent Medicine HIV/AIDS Research Network contributed blood samples. Samples selected for the cross-sectional data set analyzed had to meet selection criteria developed to minimize the potential confounding effects of acute intercurrent illnesses or infections, recent vaccination for hepatitis, and altered hormone status and to optimize congruence of cytokine measurements with assays of viral load and CD4(+)-T-cell counts. Group differences in the proportions of subjects with detectable levels of each cytokine marker were compared. In the subset of subjects with detectable cytokine values, differences in detected values were compared across subgroups defined by HIV serostatus and among HIV-seropositive subjects by three viral load classifications. The study sample was 65% HIV seropositive, 71% African-American, and 75% female with a mean age of 17.4 years. HIV-seropositive subjects were relatively healthy with mean and median CD4(+)-T-cell counts of 534 and 499 cells/mm(3), respectively. Only 8.1% of subjects had CD4(+)-T-cell counts below 200 cells/mm(3), and 25% had viral loads that were below the threshold of detection (<400 copies/ml). Detailed analyses of these data indicate that there were no differences in cytokines detected in HIV-seropositive and HIV-seronegative adolescents, and there was no apparent relationship between the cytokine measurements and the viral load or CD4(+)-T-cell categorization, the parameters selected as markers of HIV-associated disease status. These adolescents, including the HIV-seropositive subjects, were relatively healthy, and the HIV-infected subjects were at an early stage in the course of their HIV-associated disease. On the basis of our data, we conclude that, early in the course of HIV-associated disease in adolescents, there are no detectable shifts from TH1 to TH2 cytokine production.     

Screening of selected male blood donors for p24 antigen of human immunodeficiency virus type 1. The Transfusion Safety Study Group

BACKGROUND. The p24 antigen of human immunodeficiency virus type 1 (HIV-1) is sometimes detected before antibody (anti-HIV-1) is detectable in the serum of recently infected persons. This has led to the consideration of p24-antigen testing for routine screening of blood donors. METHODS. To estimate how many HIV-infected seronegative donors would be identified if p24-antigen screening was introduced, we tested selected donations from a repository of 200,000 serum samples from voluntary donors that was established in late 1984 and early 1985. The 8597 serum samples selected for p24-antigen screening were chosen because their donors had demographic characteristics known to be associated with a high prevalence of seropositivity. RESULTS. The prevalence of anti-HIV-1 antibodies in the 1984-1985 serum samples selected for p24-antigen screening was 1.54 percent--more than 100 times the 0.012 percent prevalence in present-day donations in the United States. The antigen was detected in 15 of 132 serum samples (11.4 percent) from donors who had already been confirmed as seropositive. No instance of confirmed positivity for p24 antigen was found among the 8465 seronegative serum samples. CONCLUSIONS. These data indicate that the yield of screening for p24 antigen in volunteer donors to identify HIV-1 carriers would be negligible. We therefore recommend against routine screening with currently available p24-antigen assays.     

Population differences in cardiovascular reactivity to the cold pressor test

The interaction of race and climatic adaptation on patterns of cardiovascular reactivity among young adult males was examined. Malay and Chinese subjects living in a tropical climate in the Orient and Caucasians living in a sub-tropical climate in North America were investigated. The cold pressor test with hand immersion in cold water was used as the stressor. Systolic and diastolic blood pressures, cardiac frequency, cardiac output, and stroke volume were measured. The results provided limited evidence for absence of differences in cardiac reactivity among racial groups and for greater vascular reactivity in the Caucasians. Cold immersion also elicited differential responses which could be partially attributed to differences in acclimatizations status. © 1995 Wiley-Liss, Inc.     

Psychophysiological Predictors of Attentional Dysfunction in Children with Congenital Heart Defects

Cardiac responses to non-signal stimuli and to signal stimuli in a vigilance task were examined in children born with congenital heart defects (CHD), and in normal and attention deficit disordered (ADD) subjects. Overall task performance was lower in subjects with heart defects and in the ADD group. Cardiac measures revealed that normal children displayed significantly larger heart rate deceleration to the target stimuli than did either of the clinical groups. Moreover, although no group differences were observed in the cardiac response to non-signal auditory stimuli, exaggerated heart rate deceleration was observed to vibrotactile stimuli in both the clinical groups. Regression analyses revealed that the magnitude of the cardiac response to somatosensory stimuli was predictive of task performance (both within and between subject groups), with larger responses associated with higher error rates and lower perceptual sensitivity. Results were suggestive of a predictive relationship between somatosensory reactivity and neuropsychological maturation.     

Characterization of a single base-pair deletion in neurofibromatosis type 1

The gene which is responsible for neurofibromatosis type 1 (NF1)is located on chromosome 17 (17q11.2). The NF1 gene is approximately350 kilobases (kb) long and exhibits an extremely high mutationrate; therefore, most patients are expected to have unique mutations.To date, relatively few mutations have been well characterized.We report here a de novo single base pair (bp) deletion in oneNF1 allele in a patient diagnosed with NF1 and leukemia. Wefurther characterized this mutation at the RNA level by allele-specificoligonucleotide (ASO) hybridization which demonstrated thatthe mutant allele is transcribed.     

Do dysfunctional cognitions mediate the relationship between risk factors and postnatal depression symptomatology?

BACKGROUND: This study investigated the mediating role of general and maternal-specific dysfunctional cognitions, in the relationship between non-cognitive risk factors and postnatal depressive symptomatology. METHODS: An Australian community sample comprising 406 postnatal women responded to the Dysfunctional Attitude Scale (DAS), the Maternal Attitudes Questionnaire (MAQ), the Vulnerable Personality Style Questionnaire (VPSQ) and the Edinburgh Postnatal Depression Scale (EPDS). They also responded to several questions related to perinatal and postnatal experiences. RESULTS: Path analysis demonstrated that different mediational pathways operated for different risk factors. The relationship between having a difficult baby and postnatal depression was fully mediated by maternal-specific dysfunctional cognitions (MAQ scores), whereas the relationship between past history of depression and postnatal depression was partially mediated by general dysfunctional cognitions (DAS scores). Finally, the relationship between a vulnerable personality and depressive symptomatology was mediated by both DAS and MAQ scores. LIMITATIONS: The study employed a correlational design. Thus, all inferences regarding possible causal pathways are tentative. In addition, the generalisability of these findings to other populations needs to be demonstrated in future research. CONCLUSIONS: The results of the study are consistent with the view that risk factors may influence postnatal depression indirectly through at least two distinct cognitive mediators (dysfunctional maternal and general cognitions). It may be possible to target therapies more effectively by identifying the relevant mediating mechanism(s) for individuals with different risk profiles.