Virginia Anderson

In utero marijuana exposure associated with abnormal amygdala dopamine D2 gene expression in the human fetus

BACKGROUND Marijuana (Cannabis sativa) is the illicit drug most used by pregnant women, and behavioral and cognitive impairments have been documented in cannabis-exposed offspring. Despite the extensive use of marijuana, very limited information exists as to the consequences of prenatal cannabis exposure on the developing human brain. METHODS We optimized an in situ hybridization histochemistry technique to visualize mRNA expression in midgestation (weeks 18-22) human fetal specimens from mothers with and without documented evidence of cannabis use during pregnancy. The cannabinoid receptor type 1 (CB(1)) and major dopamine receptor subtypes, D(1) and D(2), were examined in the striatum and mesocorticolimbic structures (amygdala and hippocampus). RESULTS Adjusting for various covariates, we found a specific reduction, particularly in male fetuses, of the D(2) mRNA expression levels in the amygdala basal nucleus in association with maternal marijuana use. The reduction was positively correlated with the amount of maternal marijuana intake during pregnancy. No significant cannabis-related alterations were detected in the hippocampus or caudal striatum for the D(2), D(1), and CB(1) mRNA levels, although alcohol showed significant contribution to striatal D(1)/D(2) expression. CONCLUSIONS These human fetal findings suggest that in utero cannabis exposure may impair distinct mesocorticolimbic neural systems that regulate emotional behavior.

Hepatic pathology in pediatric acquired immunodefiency syndrome

In a retrospective study we assessed the hepatic changes in children with the acquired immunodeficiency syndrome by reviewing 12 biopsy specimens and 48 autopsy specimens from 54 children. Hepatopathology differed in biopsy and autopsy material. In biopsy specimens, chronic active hepatitis with predominantly T8 lymphocytes by tissue immunochemistry was common (five of 12 specimens). Fatty degeneration and hepatocellular necrosis were either absent, mild, or patchy. On the other hand, at autopsy, chronic active hepatitis was not observed. The most prominent changes were extensive fatty degeneration, nonspecific portal mononuclear infiltration, portal fibrosis, and confluent (ischemic) necrosis. Opportunistic infections such as Mycobacterium avium-intracellulare (MAI) were noted only at autopsy. In addition, three unusual morphologic characteristics were noted: nodular lymphoplasmacytic portal infiltrate, a pseudosarcomatous variant of Mycobacterium avium-intracellulare infection, and multinucleated giant cells (foreign both type and giant cell transformation of hepatocytes).

Opportunistic Infections in Pediatric HIV Infection: A study of 74 Autopsy Cases from Latin America: The Latin American AIDS Pathology Study Group

The present report describes opportunistic infections found at 74 autopsies of pediatric HIV/AIDS patients performed at several hospitals in Latin American countries. Fungal infections were the most common (53 cases), Candida sp. (39.18%) and Pneumocystis carinii (20.27%) being the most frequently recognized. Other fungal diseases included histoplasmosis, aspergillosis, and cryptococcosis. Viral infections were present in 31 cases, 38.7% being due to cytomegalovirus. Other viruses recognized included herpes simplex and adenovirus. Additional opportunistic infections were due to Mycobacterium avium-intracellulare, toxoplasmosis, and tuberculosis. Nonspecific bacterial bronchopneumonia was present in 11 cases. Cytomegalovirus and P. carinii coinfection was the most common association found. In this series patients died at a younger age (72% at or younger than 1 year old) and there was a slightly higher number of cases of histoplasmosis and brain toxoplasmosis than in other previously published series of infants and children.

Ischemic injury to newborn rabbit ileum: Protective role of human superoxide dismutase

The effectiveness of human superoxide dismutase (hSOD) in the prevention of reperfusion injury was evaluated in a rabbit ileal loop model. Weanling white New Zealand rabbits, 6 weeks of age and weighing 500 to 1,000 g, were used. Intraluminal administration of SOD (5 mg/kg) was studied in 12 animals with each animal serving as its own control. In an additional 12 animals, parenteral SOD in a dose of 5 mg/kg in seven animals and 10 mg/kg in five animals was evaluated, while five additional control animals received parenteral saline. The effect of reperfusion injury was evaluated in each bowel loop by interruption of blood supply for five minutes, followed by reperfusion. Blood was drawn at 0, 16, 20, 24 hours in the parenteral group for measurement of hSOD levels by radioimmunoassay. The loops were studied pathologically for extent of mucosal damage. In the intraluminal group, nine of 12 loops without SOD v three of 12 loops with SOD showed necrosis when rendered ischemic (P = .0196). In the parenteral group 22 of 24 loops were normal when pretreated with SOD and subjected to ischemia v five of ten when no SOD was given (P = .0139). In the parenteral group, mean baseline level of hSOD was 0.42 +/- 0.26 micrograms/mL. Levels peaked at 16 hours (3.64 +/- 1.75 micrograms/mL) and progressively decreased at 20 hours (2.85 +/- 1.34 micrograms/mL) and 24 hours (1.82 +/- 1.15 micrograms/mL). This preliminary animal study suggests that hSOD may be an effective method for the prevention of postischemic bowel injury, adding to the literature on the protective effects of SOD in various models of intestinal ischemia.

Inverse Correlation Between Helicobacter pylori Colonization and Obesity in a Cohort of Inner City Children

Recently, publications in adults and children have documented a potential role of Helicobacter pylori (H. pylori) in decreasing the likelihood of obesity. The present study compares the prevalence of H. pylori colonization between obese (body mass index [BMI] ≥ 95th percentile) and healthy weight (BMI ≥ 5th to <85th percentiles) children seen at an inner city medical center in the United States.

ω-3 Fatty Acids Prevent Hepatic Steatosis, Independent of PPAR-α Activity, in a Murine Model of Parenteral Nutrition–Associated Liver Disease

OBJECTIVES ω-3 Fatty acids (FAs), natural ligands for the peroxisome proliferator-activated receptor-α (PPAR-α), attenuate parenteral nutrition-associated liver disease (PNALD). However, the mechanisms underlying the protective role of ω-3 FAs are still unknown. The aim of this study was to determine the effects of ω-3 FAs on hepatic triglyceride (TG) accumulation in a murine model of PNALD and to investigate the role of PPAR-α and microsomal triglyceride transfer protein (MTP) in this experimental setting. METHODS 129S1/SvImJ wild-type or 129S4/SvJaePparatm/Gonz/J PPAR-α knockout mice were fed chow and water (controls); oral, fat-free PN solution only (PN-O); PN-O plus intraperitoneal (IP) ω-6 FA-predominant supplements (PN-ω-6); or PN-O plus IP ω-3 FA (PN-ω-3). Control and PN-O groups received sham IP injections of 0.9% NaCl. Hepatic histology, TG and cholesterol, MTP activity, and PPAR-α messenger RNA were assessed after 19 days. RESULTS In all experimental groups, PN feeding increased hepatic TG and MTP activity compared with controls. Both PN-O and PN-ω-6 groups accumulated significantly greater amounts of TG when compared with PN-ω-3 mice. Studies in PPAR-α null animals showed that PN feeding increases hepatic TG as in wild-type mice. PPAR-α null mice in the PN-O and PN-ω-6 groups demonstrated variable degrees of hepatic steatosis, whereas no evidence of hepatic fat accumulation was found after 19 days of oral PN plus IP ω-3 FAs. CONCLUSIONS PN induces TG accumulation (steatosis) in wild-type and PPAR-α null mice. In PN-fed wild-type and PPAR-α null mice given IP ω-3 FAs, reduced hepatic TG accumulation and absent steatosis are found. Prevention of steatosis by ω-3 FAs results from PPAR-α-independent pathways.

Ileal immune dysregulation in necrotizing enterocolitis: role of CD40/CD40L in the pathogenesis of disease.

Objectives: CD40, a co-stimulatory molecule, plays a critical role in coordinating enteric inflammatory immune responses. In necrotizing enterocolitis (NEC), upregulation of IL-10, a CD40-modulated cytokine, has been described, but the role of the IL-10 receptor (IL-10Rβ), CD40, and its ligand CD40L in disease pathogenesis is unknown. The study herein investigates ileal expression of CD40, CD40L, and IL-10R in a rat model of NEC. Subjects and Methods: NEC was induced in newborn rats using established methods of formula feeding, asphyxia, and cold stress. Expression of CD40, CD40L, IL-10Rβ, and other proinflammatory molecules, including Toll-like receptor-4 (TLR-4) and IL-18, was assessed by immunoblotting. Tissue infiltration by macrophages, monocytes, and T cells was examined by confocal immunohistochemistry. Results: Ileum from rat pups with NEC showed increased expression of TLR-4, IL-18, and IL-10Rβ. Sections from both NEC and control pups demonstrated preservation of ileal cells expressing CD40/CD40L. The distal ileum of controls expressed both CD40 and CD40L; conversely, neither molecule was detected in ileal tissue from NEC pups. Additional studies showed that treatment with epidermal growth factor (EGF), previously shown to ameliorate the severity of NEC in an animal model, did not restore CD40 expression. Conclusions: Ileal cytokine dysregulation, manifested by decreased CD40/CD40L and increased IL-10Rβ expression, may be involved in the pathogenesis of NEC. Dampened CD40 signaling may be related to enhanced IL-10 expression and a suppressed T-cell response to injury. We speculate that augmenting CD40-CD40L interactions may achieve a protective effect in this NEC model.

Intestinal Cytomegalovirus Ganglioneuronitis in Children with Human Immunodeficiency Virus Infection

Cytomegalovirus in children with human immunodeficiency virus (HIV) infection can result in widespread involvement of enteric ganglion cells. Intestinal ganglioneuronitis, as noted in the two infants cited, expands the spectrum of neurologic lesions in children with acquired immunodeficiency syndrome (AIDS).

Microwave Immunohistochemistry: Advances in Temperature Control

The advantages and limitations to employing a fiber-optic temperature probe for feedback control of a microwave oven designed for immunohistochemistry were tested. The probe was designed to be submerged in a drop of immunoreagent on a glass slide, and the measured temperature of the droplet was used to regulate the output power and the time needed for the magnetron to reach and maintain the desired incubation temperature. A three-step streptavidin-biotin-peroxidase microwave method, employing a range of antibodies, particularly anti-insulin on rat pancreas, was used as the model system to illustrate the effect of temperature and duration of incubation in microwave immunostaining. Insight into the factors affecting a droplet temperature under microwave irradiation and the relationship among temperature, duration, concentrations of antibodies and immunoreaction for immunostaining were obtained. The optimal temperature and duration for microwave immunostaining in our model system were 37°C for 3 min at 75% power level followed by a 2-min incubation inside the oven for all three stages of immunostaining. Use of droplet temperature-regulated microwave standardizes conditions used in microwave immunohistochemistry. Other potential applications where uniform heating of small amounts of reagent and control of reagent temperature are important may benefit from this technique.

Case Report: Endoscopic Features of Intestinal Smooth Muscle Tumor in a Child with AIDS

Intestinal leiomyosarcomas are exceedingly rare in immunologically intact children, except during infancy. While leiomyosarcomas account for less than 2% of all soft tissue tumors in childhood, they are the second most frequent malignancy in children with the acquired immunodeficiency syndrome (AIDS). In this cohort they are often located in unusual sites for primary soft tissue tumors. This report describes a young girl with advanced AIDS, referred for evaluation of abdominal pain, hematochezia, and wasting syndrome. Colonoscopy revealed two 1- to 2-cm submucosal nodules with central umbilication. Repeat colonoscopy 18 months later revealed no changes in these lesions. Biopsy revealed a submucosal spindle-cell lesion, with necrosis and cellular atypia. Initially it was characterized as a partially excised low-grade leiomyosarcoma. However, the final consensus diagnosis was smooth muscle tumor of uncertain malignant potential. Because of her advanced AIDS, there was no attempt at surgical resection or chemotherapy. Thirty-six months after initial referral, she remains alive without radiographic or clinical evidence of local extension or metastases. Additional data are required to determine the long-term outcome of these indolent submucosal tumors in the digestive tracts of children with AIDS.