Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is associated with mucosal damage in SIV infection.

Human immunodeficiency virus (HIV) and Simian immunodeficiency virus (SIV) disease progression is associated with multifocal damage to the gastrointestinal tract epithelial barrier that correlates with microbial translocation and persistent pathological immune activation, but the underlying mechanisms remain unclear. Investigating alterations in mucosal immunity during SIV infection, we found that damage to the colonic epithelial barrier was associated with loss of multiple lineages of interleukin (IL)-17-producing lymphocytes, cells that microarray analysis showed expressed genes important for enterocyte homeostasis, including IL-22. IL-22-producing lymphocytes were also lost after SIV infection. Potentially explaining coordinate loss of these distinct populations, we also observed loss of CD103+ dendritic cells (DCs) after SIV infection, which associated with the loss of IL-17- and IL-22-producing lymphocytes. CD103+ DCs expressed genes associated with promotion of IL-17/IL-22+ cells, and coculture of CD103+ DCs and naïve T cells led to increased IL17A and RORc expression in differentiating T cells. These results reveal complex interactions between mucosal immune cell subsets providing potential mechanistic insights into mechanisms of mucosal immune dysregulation during HIV/SIV infection, and offer hints for development of novel therapeutic strategies to address this aspect of AIDS virus pathogenesis.

Chronic cocaine exposure during pregnancy increases postpartum neuroendocrine stress responses.

The cycle of chronic cocaine (CC) use and withdrawal results in increased anxiety, depression and disrupted stress-responsiveness. Oxytocin and corticosterone (CORT) interact to mediate hormonal stress responses and can be altered by cocaine use. These neuroendocrine signals play important regulatory roles in a variety of social behaviours, specifically during the postpartum period, and are sensitive to disruption by CC exposure in both clinical settings and preclinical models. To determine whether CC exposure during pregnancy affected behavioural and hormonal stress response in the early postpartum period in a rodent model, Sprague-Dawley rats were administered cocaine daily (30 mg/kg) throughout gestation (days 1-20). Open field test (OFT) and forced swim test (FST) behaviours were measured on postpartum day 5. Plasma CORT concentrations were measured before and after testing throughout the test day, whereas plasma and brain oxytocin concentrations were measured post-testing only. The results obtained indicated increased CORT response after the OFT in CC-treated dams (P ≤ 0.05). CC-treated dams also exhibited altered FST behaviour (P ≤ 0.05), suggesting abnormal stress responsiveness. Peripheral, but not central, oxytocin levels were increased by cocaine treatment (P ≤ 0.05). Peripheral oxytocin and CORT increased after the FST, regardless of treatment condition (P ≤ 0.05). Changes in stress-responsiveness, both behaviourally and hormonally, may underlie some deficits in maternal behaviour; thus, a clearer understanding of the effect of CC on the stress response system may potentially lead to treatment interventions that could be relevant to clinical populations. Additionally, these results indicate that CC treatment can have long-lasting effects on peripheral oxytocin regulation in rats, similar to changes observed in persistent social behaviour and stress-response deficits in clinical populations.

Unwanted childbearing, health, and mother-child relationships.

This paper investigates the relationships among unwanted childbearing, health, and mother-child relationships. We hypothesize that unwanted childbearing affects mother-child relationships in part because of the physical and mental health consequences of unwanted childbearing. Impaired mental health hampers women's interaction with their infants, and these poor neonatal relationships translate into poor mother-adult child relationships. Using the Intergenerational Panel Study of Mothers and Children--a 31-year longitudinal survey of a probability sample of 1,113 mother-child pairs begun in 1961--we demonstrate that mothers with unwanted births have lower quality relationships with their children from late adolescence (age 18) throughout early adulthood (ages 23 and 31). Furthermore, these lower quality relationships are not limited to the child born as a result of the unwanted pregnancy; all the children in the family suffer. Using the 1987-88 wave of the National Survey of Families and Households, a survey of a national probability sample of U.S. households, we show that mothers with unwanted births suffer from higher levels of depression and lower levels of happiness. We also demonstrate that they spank their young children more and spend less leisure time with them. We conclude that experiencing unwanted childbearing reduces the time and attention that mothers give their young children and that these early mother-child interactions set the stage for long-term, lower quality relationships.

The long-term impact of parents' childbearing decisions on children's self-esteem.

We examine the long-term impact of parents' childbearing decisions on children's self-esteem. We focus on subjective aspects of the home environment in the creation of children's internalized sense of self-worth. Unique 23-year family panel data combining measures of mothers' childbearing, mothers' childbearing intentions, and children's self-esteem allow us to examine the overall links between parents' childbearing and children's self-esteem. The results demonstrate that parents' childbearing intentions can have a significant long-term impact on their children's self-esteem. Children who were unintended by their mothers have significantly lower self-esteem 23 years later. Our findings indicate that giving birth to an unintended child can have a long-term negative impact on subjective aspects of the child's well-being, at least in terms of self-esteem. Unintended childbearing has received an increasing amount of research attention in recent years.

Naturally occurring vertical transmission of Neospora caninum in dogs.

Vertical transmission of Neospora caninum was studied in naturally infected, privately owned dogs, using antibody detection by IFAT to identify infected individuals. Retrospective studies were undertaken in litters from six bitches of the Hamiltonstövare breed, and on litters from seven bitches of other breeds--in both cases following diagnosis of clinical disease in puppies--and prospective studies were carried out on 17 seropositive bitches of other breeds. Puppies were classified as infected if either pre-colostral sera, or serum taken at > or = 5 weeks, had a titre of > or = 1:50 in the IFAT. The frequency of putative congenital transmission was variable; three seropositive dams produced successive litters, each containing seropositive puppies; four other seropositive bitches, which each whelped twice, produced six litters in which all pups were seronegative. Bitches born to seropositive dams themselves produced litters containing seropositive pups. In the retrospective studies, 32/61 (52%) of pups tested born to 13 seropositive dams were themselves seropositive and 22/88 (25%) of all pups born developed clinical signs compatible with a diagnosis of neosporosis. However, in the prospective study, only 4/118 (3%) pups tested from 17 seropositive dams were seropositive and 4/122 (3%) of all pups born developed signs consistent with neosporosis. This difference reflected levels of IFAT titre in the two groups of bitches and overall the proportion of pups seropositive was strongly and positively correlated (r = 0.980, P < 0.05) with bitch IFAT titre. Overall, 80% of pups born to seropositive dams were not infected as determined serologically. This study shows that the frequency of vertical transmission of naturally acquired Neospora infection in dogs is variable, but much too low to sustain infection alone. Post-natal infection must occur to maintain infection at seroprevalence rates reported in dog populations.

Prevalence of antibodies to Neospora caninum in different canid populations.

A total of 1,554 dogs from 5 countries on 3 continents were tested for antibodies to Neospora caninum using an indirect fluorescent antibody test. In Australia, overall, 42/451 (9%, 95% confidence interval [CI] 6-12%) dogs were seropositive (Melbourne 11/207 [5%, 95% CI 2-9%]; Sydney 18/150 [12%, 95% CI 7-18%]; Perth 13/94 [14%, 95% CI 8-22%]). Antibodies to N. caninum were also detected in dogs in South America (Uruguay [20%, 95% CI 16-24%, n = 414]) and sub-Saharan Africa (Tanzania [22%, 95% CI 12-36%, n = 49]). In contrast, only 1 of 500 dogs tested from the Falkland Islands and none of 140 dogs from Kenya was seropositive. Of wild canids, 1/54 (2%, 95% CI 0-10%) British foxes and 15/169 (9%, 95% CI 5-14%) Australian dingoes had antibodies to N. caninum.

Seroprevalence of antibodies to Neospora caninum in Belgian dogs.

Sera from 300 dogs from Ghent and Antwerp were tested for antibodies to Neospora caninum using an indirect fluorescent antibody test. Overall, 11 per cent (9.5 to 13 per cent; confidence interval of 95 per cent) of dogs were seropositive, at titres of 1:50 to 1:800. No sex or breed differences were detected, but there was an increase in seropositivity with age.

The neighborhood history calendar: a data collection method designed for dynamic multilevel modeling.

"This paper presents a new data collection method, called the Neighborhood History Calendar, designed to collect event histories of community-level changes over time. We discuss the need for and the uses of this method. We describe issues related to the design of instruments, collection of data, and data entry. We provide detailed examples from an application of this method to the study of marriage, contraception, and fertility in rural Nepal. The paper addresses applications of this same technique to other settings and research problems. We also extend the technique to collection of other forms of contextual-history data, including school histories and health service histories. Finally, we discuss how Geographic Information System (GIS) technology can be used to link together multiple sources of contextual-history data."

Distribution of Neospora caninum within the central nervous system and other tissues of six dogs with clinical neosporosis.

Six cases of neosporosis in dogs were diagnosed on the basis of clinical signs, serology and immunohistochemistry. The brains and spinal cords, at several levels, and various other tissues were examined using anti-Neospora caninum serum by an immunoperoxidase technique. Parasite density varied markedly from case to case. Although found most consistently in the cerebrum, parasites were distributed throughout the central nervous system (CNS), both within the grey and white matter and within nerve roots. Clinical signs were not related to the position of parasites. Tissue cysts were found infrequently in all areas of the CNS, but not in other tissues. Parasite density was not related to the age of the dog or whether treatment had been given. However, with the exception of the only adult dog examined, more CNS parasites were found in dogs with a longer duration of illness and with higher antibody titres. Tachyzoites were present in skeletal muscles, in the muscularis of the oesophagus, in heart, lung and, less frequently, liver, and rarely in the adrenal gland, thyroid gland and uterus; no clinical signs were seen resulting from damage to these organs. Parasites were not observed in lymphoid tissue. In visceral organs, parasites were most widely distributed in peracute cases. For post mortem diagnosis of neosporosis, the CNS, particularly the cerebrum, is the optimum tissue to examine but parasites may also be found in many other tissues, especially in acute cases. Muscle biopsy of appropriate muscles (as suggested by the clinical signs) provides the possibility of a definitive premortem diagnosis.

Clinical aspects of 27 cases of neosporosis in dogs.

Twenty-seven cases of neosporosis in European dogs are described. The disease was confirmed by immunohistochemistry, electron microscopy, or a favourable response to treatment in the dogs with appropriate clinical signs, and by the presence of antibodies to Neospora caninum but not to Toxoplasma gondii. The affected dogs were two days to seven years old, and of 13 different breeds. Both sexes were affected and in most cases littermates remained normal. Twenty-one cases had an initial hindlimb paresis or ataxia, in which muscle atrophy was the most consistent clinical sign. Rigid hyperextension developed in approximately half of the cases. Anorexia and pyrexia were rare. Other clinical signs included forelimb ataxia, head tremors with tetraparesis and sudden collapse due to myocarditis. Titres of > or = 1:800 in the N caninum indirect fluorescent antibody test were detected in the 20 cases from which serum samples were taken. Such high titres are rare in healthy dogs and strongly suggest a diagnosis of neosporosis. Sixteen of the dogs received appropriate antiprotozoal treatment with clindamycin, potentiated sulphonamides and/or pyrimethamine; 10 made a full or functional recovery. Recovery was less likely in peracute cases with severe clinical signs, and when the treatment was delayed.

Expression of the messenger ribonucleic acids for insulin-like growth factor-I and insulin-like growth factor binding proteins in porcine corpora lutea.

In the pig, the corpus luteum (CL) can develop and function autonomous of pituitary gonadotropins for approximately 12 days. We hypothesized that the insulin-like growth factor (IGF) system may play an autocrine/paracrine luteotrophic role(s) during this period. In this study, we monitored the expression (i.e., steady-state levels of mRNAs) of IGF-I and IGF binding proteins (IGFBP)-2, -3, -4, -5, and -6 mRNAs in whole CL and in small and large luteal cells on Days 4-16 of the estrous cycle. CL were dissociated with collagenase, and large and small luteal cells were isolated by centrifugal elutriation. Whole CL and luteal cells were extracted to isolate total or poly(A)+ RNA, which was subjected to Northern and/or dot-blot analyses using [32P]-labeled cDNA probes for IGF-I and IGFBP-2, -3, -4, -5, and -6. Northern blots showed readily detectable transcripts for IGF-I (6.7 and 0.9 kb), IGFBP-2 (1.8 kb), IGFBP-3 (2.8 kb), IGFBP-4 (2.6 kb), and IGFBP-5 (6.0 kb), but not for IGFBP-6. IGFBP-3 and -5 transcripts were observed mainly in small luteal cells, while IGFBP-2 and -4 were seen in both cell types. Dot-blot analyses for IGF-I and IGFBP-3 mRNAs were performed on total RNA from small and large luteal cells; blots were counter-probed with 3-phosphoglyceraldehyde dehydrogenase (p-GAD) cDNA to assess RNA quantity and quality. IGF-I mRNA (ratio IGF-I:p-GAD mRNA) expression was approximately 2-fold greater in small than in large luteal cells on Days 4-10. However, steady-state levels of IGF-I mRNA in small, but not large, luteal cells decreased significantly on Days 12-16 (vs. Days 4-10). IGFBP-3 mRNA expression was significantly greater (approximately 3-fold) in small than in large luteal cells but did not vary significantly between Days 4-10 and 12-16 for either cell type. We conclude that porcine CL express mRNAs for IGF-I and IGFBP-2, -3, -4, and -5, and that while small luteal cells are the major sources of IGF-I and IGFBP-3 and -5, IGFBP-2 and -4 appear to be expressed to approximately the same extent in small and large luteal cells. These results further suggest that the IGF-I/IGF system may have autocrine/paracrine regulatory actions in CL development/function in the pig.

Characterization of the first European isolate of Neospora caninum (Dubey, Carpenter, Speer, Topper and Uggla).

Neospora caninum is an apicomplexan, protozoan parasite, which causes severe disease in dogs and cattle. It has previously been isolated only in the United States. A 5-week-old Boxer pup with a progressive hindlimb paresis was diagnosed as suffering from neosporosis on the basis of clinical signs and the presence of anti-Neospora antibodies in it, 2 litter-mates and its dam. Despite treatment with sulphonamides, the pup was euthanased 3 days later. The diagnosis of neosporosis was confirmed by immunohistochemical examination of muscle and CNS tissue sections from the pup. Parasites were isolated into Vero cell culture from the cerebrum, and confirmed as Neospora caninum by immunofluorescence with specific antibody, tachyzoite ultrastructure and 16S-like ribosomal RNA sequences. This isolate (designated NC-Liverpool) has been continuously passaged every 7-10 days. Its growth characteristics, ultrastructure and antigenic profile, as revealed by immunoblotting, have revealed no major differences from the American NC-1 isolate. Furthermore, no difference was seen when comparing the sequences of 16S-like ribosomal RNA and the ITS1 region of the two isolates.