A tortuous proximal urethra in urorectal septum malformation sequence?

We observed a newborn boy with urorectal septum malformation sequence. Anomalies of the genitalia and rectum were present. He expired on the first day of life, due to severe lung hypoplasia. Autopsy showed a colon that ended in a blind sac, an enlarged bladder with no grossly visible urethra, and dysplastic kidneys. A cone-shaped tissue at the usual site of the bladder outlet contained tortuous and slit-like lumina, suggesting an undeveloped proximal urethra. The urethral structure was lined by transitional epithelium with squamous metaplasia. Many small buds-lined with columnar epithelium-branched from the urethral structure. These ductal buds lined with columnar epithelium stained for prostatic acid phosphatase. Basal cells surrounding the ductal buds stained for p63 and high molecular weight cytokeratin-supporting an interpretation that the buds were early prostatic ducts with normal histology. To our knowledge, these are the first histological images of an undeveloped, obstructed urethra associated with the urorectal septum malformation sequence.

Subcutaneous Panniculitis-like T-cell lymphoma in two pediatric patients: an HIV-positive adolescent and a 4-month-old infant.

Subcutaneous Panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of childhood non-Hodgkin lymphoma. Subcutaneous Panniculitis-like T-cell lymphoma has an aggressive variant associated with the hemophagocytic syndrome (HPS). Patients without HPS show resolution of the disease with prednisone or immunosuppressive therapy unlike other T-cell lymphomas. One HIV-positive adolescent and one infant with multiple subcutaneous masses are presented and the literature is reviewed. Lesional cells were consistent with SPTCL alpha-beta type. Our cases, without HPS, showed complete resolution of their lesions when treated with non-aggressive therapies. Patients with SPTCL alpha-beta should be treated conservatively.

Unequivocal identification of brown adipose tissue in a human infant.

We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.

Cyclic adenosine monophosphate induces plasminogen activator inhibitor-1 expression in human mast cells.

Plaminogen activator inhibitor-1 (PAI-1), the key physiological inhibitor of the plasmin fibrinolytic system, plays important roles in the pathogenesis of asthma. Mast cells (MCs) are crucial effector cells and a major source of PAI-1 for asthma. Cyclic adenosine monophosphate (cAMP) is the important regulator of MCs; however, its effects on PAI-1 expression in MCs remain unknown. We reported cAMP/protein kinase A pathway positively regulates PAI-1 expression through cAMP-response element binding protein binding to hypoxia response element-1 at -158 to -153bp of human PAI-1 promoter in human MCs. Moreover, cAMP synergistically augments PAI-1 expression with ionomycin- or IgE receptor cross-linking-mediated stimulation.

Pimecrolimus induces apoptosis of mast cells in a murine model of cutaneous mastocytosis.

BACKGROUND: Cutaneous mastocytosis (CM) is a common type of mastocytosis. Current treatment of CM is generally symptomatic. Pimecrolimus has been demonstrated as an effective anti-inflammatory drug for the treatment of inflammatory skin diseases, but whether it treats CM remains unknown. METHODS: The murine model of CM was induced by subcutaneous injection of 100 µg/kg recombinant murine stem cell factor (rmSCF) for a total of 17 days in Balb/c mice. Beginning on the 8th day, treatment with pimecrolimus 1% cream or vehicle was performed topically and daily for 10 days. The clinical signs of CM were scored, and pathological analysis was performed with toluidine blue staining and hematoxylin and eosin staining. The in situ apoptotic mast cells (MCs) were studied by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. The cutaneous histamine level was measured by ELISA. RESULTS: In the rmSCF-treated mice, the clinical signs of CM, including erythema, wheal after rubbing lesion skins, and increased thickness of skin, were obvious compared to control mice, and were reduced after pimecrolimus treatment. The numbers of cutaneous MCs and neutrophils were significantly greater in mice with CM than in control mice, and pimecrolimus treatment decreased the numbers of MCs but not neutrophils. Extensive apoptosis of cutaneous MCs was observed in pimecrolimus-treated mice. The cutaneous histamine level was elevated in the mice with CM compared with healthy controls, and was lowered after treatment with pimecrolimus. CONCLUSIONS: Pimecrolimus effectively treats CM by reducing the density of cutaneous MCs and the subsequent histamine production through inducing MCs apoptosis.