Elsa Valderrama

Langerhans' cell histiocytosis

Langerhans cell histiocytosis is a disease caused by the monoclonal proliferation of Langerhans cells. Langerhans cell histiocytosis may involve bone, skin, lymph nodes, liver and spleen, with haematologic changes, and cause fever, malaise and failure to thrive. Up to 50% of patients with either single or multi-organ manifestation of Langerhans cell histiocytosis initially present with cutaneous symptoms. Cutaneous Langerhans cell histiocytosis is heterogeneous in its clinical features and therefore prone to misdiagnosis. We report here a case of Langerhans cell histiocytosis in a child who presented with multiple scalp lesions, in whom a presumptive diagnosis of Langerhans cell histiocytosis is made when characteristic histomorphological features are identified on biopsy tissue, and the definitive diagnosis is established by immunohistochemical examination with appropriate antibodies.

DEC-205–Mediated Internalization of HIV-1 Results in the Establishment of Silent Infection in Renal Tubular Cells

HIV-1 infection of renal cells has been proposed to play a role in HIV-1-associated nephropathy. Renal biopsy data further suggest that renal tubular cells may serve as reservoir for HIV-1. The mechanism by which HIV-1 enters these cells has not been identified. Renal tubular cells do not express any of the known HIV-1 receptors, and our results confirmed lack of the expression of CD4, CCR5, CXCR4, DC-SIGN, or mannose receptors in tubular cells. The aim of this study, therefore, was to determine the mechanism that enables viral entry into renal tubular cells. An in vitro model was used to study the HIV-1 infection of human kidney tubular (HK2) cells and to identify the receptor that enables the virus to enter these cells. Results of these studies demonstrate that the C-type lectin DEC-205 acts as an HIV-1 receptor in HK2 cells. Interaction of HIV-1 with DEC-205 results in the internalization of the virus and establishment of a nonproductive infection. HIV-1-specific strong-stop DNA is detected in the infected HK2 cells for at least 7 d, and the virus can be transmitted in trans to sensitive target cells. HIV-1 entry is blocked by pretreatment with specific anti-DEC-205 antibody. Moreover, expression of DEC-205 in cells that lack the DEC-205 receptors renders them susceptible to HIV-1 infection. These findings suggest that DEC-205 acts as an HIV-1 receptor that mediates internalization of the virus into renal tubular cells, from which the virus can be rescued and disseminated by encountering immune cells.

Vitamin E ameliorates renal injury in an experimental model of immunoglobulin A nephropathy.

IgA nephropathy is one of the most common forms of glomerular disease. Nearly 25% of affected patients progress to end-stage renal disease over a 20-25-y follow-up period. IgA-containing immune complexes stimulate oxygen-free radical production by mesangial cells in vitro. The excessive oxidant stress may mediate glomerular injury in this disorder. Therefore, we studied whether dietary supplementation with the antioxidant agent, vitamin E, attenuates renal disease in an experimental model of incipient IgA nephropathy with mild kidney inflammation. IgA nephropathy was induced in male Lewis rats by oral immunization with 0.1% bovineγ-globulin (BGG)-containing drinking water for 8 wk. At the completion of this period, animals received BGG, 1 mg/dose i.v., on three successive days. Experimental rats (n = 10) received a specially formulated diet containing 100 IU of vitamin E/kg of chow, whereas control animals(n = 10) were fed chow containing 30 IU of vitamin/kg of chow. The BGG immunization regimen induced mesangial IgA deposition in all rats. Vitamin E supplementation resulted in a nearly 5-fold increase in the serum vitamin E concentration. Vitamin E-treated rats gained more weight and had a lower incidence of hematuria, 20% versus 80% (p < 0.03). Moreover, proteinuria was decreased by 50%, and reduced renal plasma flow was restored to normal, compared with untreated rats with IgA nephropathy. Glomerular hypertrophy occurred in animals with IgA nephropathy, but less so in those receiving vitamin E supplementation. Renal cortical malondialdehyde content was reduced from 1.55 ± 0.10 to 1.22 ± 0.09 nmol/mg of protein (p < 0.01) in rats fed the vitamin E-enriched diet. Finally, renal transforming growth factor-β1 gene expression was reduced by 34% in rats with IgA nephropathy receiving vitamin E treatment (p< 0.05). We conclude that experimental IgA nephropathy is associated with increased renal oxidant injury. Dietary treatment with the antioxidant agent, vitamin E, attenuated renal functional and structural changes in this experimental glomerulopathy. These studies support the importance of clinical trials for the evaluation of the efficacy of antioxidant therapy in patients with IgA nephropathy.

Nitric oxide and inflammatory bowel disease: evidence for local intestinal production in children with active colonic disease.

BACKGROUNDnActive colitis in patients with inflammatory bowel disease is associated with mucosal vasodilation, increased intestinal permeability and abnormal colonic motility. Nitric oxide is a messenger molecule with many functions, including regulation of local blood flow, vasomotor tone, and inflammation. Increased nitric oxide production and inducible nitric oxide synthase activity have been demonstrated in experimental models of colitis. This study was designed to determine the relationship between nitric oxide production and colonic inflammation in children with active colitis and in control subjects and whether expression of inducible nitric oxide synthase protein is demonstrable in the intestinal epithelium of these patients.nnnMETHODSnNitrate + nitrite were measured in urine, stool, and plasma using the Griess assay. Expression of inducible nitric oxide synthase protein in intestinal tissue was determined by immunohistochemical localization.nnnRESULTSnUrinary nitrate + nitrite levels were not significantly different in patients and control subjects. In contrast, stool and plasma nitrate + nitrite concentrations were significantly higher in children with inflammatory bowel disease compared with levels in control children (stool: 162.4 +/- 31.0 mumol/l versus 77.2 +/- 22.1 mumol/l; plasma: 65.2 +/- 9.9 mumol/l versus 38.1 +/- 6.6 mumol/L; p < 0.05). Stool nitrate + nitrite levels significantly correlated with plasma values. Immunohistochemical staining of colonic tissue from children with inflammatory bowel disease demonstrated inducible nitric oxide synthase protein located exclusively in epithelial cells.nnnCONCLUSIONnIncreased nitric oxide production and enhanced intestinal epithelial cell expression of inducible nitric oxide synthase protein are associated with active colonic inflammation.

Chondroid chordoma: Electron-microscopic study of two cases

Chondroid chordoma is an unusual tumor composed of an admixture of chondromatous and chordomatous tissue usually located in the spheno-occipital region. This tumor shares many of the clinical and histologic features of classic chordoma and chondrosarcoma and has been shown to have a better prognosis than either of these lesions. To the best of our knowledge, no ultrastructural studies have been performed in the 26 cases of chondroid chordoma published previously. We document the ultrastructural features of two examples of chondroid chordoma. Certain features such as prominent and dilated rough endoplasmic reticulum, intracytoplasmic glycogen aggregates, and abundant fibrillogranular matrix are common to chordoma, chondrosarcoma, and chondroid chordoma. The presence of well-formed tonofilament desmosome complexes as well as complexes composed of alternating profiles of rough endoplasmic reticulum and mitochondria were seen only in chordoma and chondroid chordoma, but not in cartilaginous tumors. Of particular interest was the finding of crystalline, tubular structures within the rough endoplasmic reticulum of both cases of chondroid chordoma, a finding not described previously. The distinction of chondroid chordoma from classical chordoma is said to be a difficult one at the light-microscopic level, and we suggest that these intraergastoplasmic tubular structures might constitute an extremely helpful differential marker.

Bartter syndrome and focal segmental glomerulosclerosis: a possible link between two diseases

Abstractu2002We describe a patient with signs and symptoms of classic Bartter syndrome. The patient tested negative for all known genetic abnormalities associated with this tubular disorder. Proteinuria was found within 1 year after the diagnosis of Bartter syndrome. A renal biopsy performed 6 months later, when her kidney function was normal, revealed focal segmental glomerulosclerosis (FSGS). We propose a link between stimulation of the renin-angiotensin system and sclerotic changes in the glomerulus. This lesion may explain previous reports of kidney failure in patients with Bartter syndrome.

Extraskeletal osteosarcoma arising in an ectopic hamartomatous thymus: Report of a case and review of the literature

A unique case of an osteosarcoma arising within a hamartoma of the thymic gland located in the left pleural cavity of an 11‐year‐old girl is described. The presence of abundant mature lamellar bone within this thymic hamartoma provides an explanation for the osseous histogenesis of the sarcoma. The development of an osteosarcoma from extraskeletal osseous tissue is a rare occurrence and has been documented in association with myositis ossificans and most recently in a case of dermatomyositis with metaplastic ossification.

Systemic necrotizing vasculitis associated with childhood sarcoidosis

Childhood sarcoidosis is a rare disorder with protean manifestations. The case of a child with prolonged fever, hepatosplenomegaly, pancytopenia, and systemic necrotizing vasculitis manifesting as fever, rash and skin infarctions, digital pregangrene, and foot drop is reported. This is the first case of systemic necrotizing vasculitis reported in sarcoidosis. The fulminant course of the disease required treatment with intravenous pulsed cyclophosphamide and high doses of corticosteroids. The spectrum of vasculitis in childhood and adult sarcoidosis is reviewed.

Leukemic meningitis in B-cell prolymphocytic leukemia. A clinical, pathologic, and ultrastructural case study and a review of the literature.

Background. Leukemic meningitis is rare in B‐chronic lymphocytic leukemia (CLL) and B‐prolymphocytic leukemia (PLL); a MEDLINE search for reports published 1960 and after disclosed only nine prior reports. A patient with stable Rai Stage II CLL/PL developed mental status changes. Lumbar puncture revealed a lymphocytic pleocytosis with prolymphocytes containing intracytoplasmic inclusions.

Panniculitis and fever in children

We describe three children with panniculitis and associated systemic manifestations including fever. Histopathologic features, such as the presence of lobular or septal inflammation, presence of vasculitis, character of the cellular infiltrate, and presence of erythrophagocytosis, were useful in classifying this group of panniculitides. In one patient with subcutaneous polyarteritis nodosa, corticosteroid therapy was effective; in two other patients with histiocytic cytophagic panniculitis, there were poor responses to steroids, intravenously administered immune globulin, dapsone, or antimalarial drugs; cyclosporine was very effective and appeared to be the drug of choice.