Jean-Pierre de Chadarévian

Hemolytic-uremic syndrome. Current concepts and management.

This article reviews recent observations that help to explain the complex pathogenesis of hemolytic-uremic syndrome, discusses the epidemiology, etiology, and the clinical picture of the syndrome, explores approaches to management, and looks at the few long-term follow-up studies of this difficult disorder.

The hemolytic uremic syndrome.

HUS is one of the most common causes of acute renal failure in childhood. D+ HUS is the most common form and usually follows an episode of hemorrhagic colitis due to VTEC or S. dysenteriae type 1. The SLT elaborated by these organisms is responsible for the endothelial damage that is the initial insult in the pathogenesis of the acute renal failure. Excellent supportive care is necessary to reduce the mortality and morbidity due to HUS.

Aberrant Localization of the Neuronal Class III b-Tubulin in Astrocytomas A Marker for Anaplastic Potential

c Background.—The class III b-tubulin isotype (bIII) is widely regarded as a neuronal marker in development and neoplasia. In previous work, we have shown that the expression of bIII in neuronal/neuroblastic tumors is differentiation dependent. In contrast, the aberrant localization of this isotype in certain nonneuronal neoplasms, such as epithelial neuroendocrine lung tumors, is associated with anaplastic potential. Objective.—To test the generality of this observation, we investigated the immunoreactivity profile of bIII in astrocytomas. Design.—Sixty archival, surgically excised astrocytomas (8 pilocytic astrocytomas, WHO grade 1; 18 diffuse fibrillary astrocytomas, WHO grade 2; 4 anaplastic astrocytomas, WHO grade 3; and 30 glioblastomas, WHO grade 4), were studied by immunohistochemistry using anti-bIII monoclonal (TuJ1) and polyclonal antibodies. A monoclonal antibody to Ki-67 nuclear antigen (NC-MM1) was used as a marker for cell proliferation. Antibodies to glial fibrillary acidic protein (GFAP) and BM89 synaptic vesicle antigen/synaptophysin were used as glial and neuronal markers, respectively. Results.—The bIII immunoreactivity was significantly greater in high-grade astrocytomas (anaplastic astrocytomas and glioblastomas; median labeling index [MLI], 35%; interquartile range [IQR], 20%‐47%) as compared with diffuse fibrillary astrocytomas (MLI, 4%; IQR, 0.2%‐21%) (P , .0001) and was rarely detectable in pilocytic astrocytomas (MLI, 0%; IQR, 0%‐0.5%) (P , .0001 vs high-grade astrocytomas; P , .01 vs diffuse fibrillary astrocytomas). A highly significant, grade-dependent relationship was observed between bIII and Ki-67 labeling and malignancy, but this association was stronger for Ki-67 than for bIII (bIII, P , .006; Ki-67, P , .0001). There was co-localization of bIII and GFAP in neoplastic astrocytes, but no BM89 synaptic vesicle antigen/synaptophysin staining was detected. Conclusions.—In the context of astrocytic gliomas, bIII immunoreactivity is associated with an ascending gradient of malignancy and thus may be a useful ancillary diagnostic marker. However, the significance of bIII-positive phenotypes in diffuse fibrillary astrocytomas with respect to prognostic and predictive value requires further evaluation. Under certain neoplastic conditions, bIII expression is not neuron specific, calling for a cautious interpretation of bIII-positive phenotypes in brain tumors. (Arch Pathol Lab Med. 2001;125:613‐624)

Thyroid antigen-antibody nephritis.

Abstract A patient with autoimmune thyroiditis developed nephrosis. Light, immunofluorescence, and electron microscopic examination of renal biopsy tissue demonstrated epimembranous nephropathy. Thyroglobulin and thyroid microsomal antigen were demonstrable in her glomeruli by indirect immunofluorescence microscopy.

Treponemal Antigens in Congenital and Acquired Syphilitic Nephritis: Demonstration by Immunofluorescence Studies

Two patients, a 4-month-old infant girl with congenital syphilis and a 45-year-old man with secondary syphilis, had the nephrotic syndrome with glomerulonephritis. Immunoglobulins and treponemal antigenic material were seen in the glomeruli of both patients by immunofluorescence microscopic studies of renal tissue. Electron micrographs showed subepithelial electron dense deposits along the glomerular basement membrane. This confirms earlier suggestions that the renal injury is of an immune-complex type.

Mollaret's Recurrent Aseptic Meningitis: Relationship to Epidermoid CystsLight Microscopic and Ultrastructural Cytological Studies of the Cerebrospinal Fluid

Cells, originally called “endothelial” cells, have been described in the cerebrospinal fluid (CSF) of patients developing recurrent aseptic meningitis (Mollarets meningitis). In an attempt at better establishing their nature, a 6-year-old child was followed for a period of 3½ years. A cytological light microscopic and ultrastructural study was performed on samples of the CSF obtained during 17 attacks. The findings are presented, and the relationship of Mollarets meningitis to intracranial epidermoid cysts is discussed.

Subependymal Giant Cell Tumor of Tuberose Sclerosis A Light and Ultrastructural Study

In a small number of cases of tuberose sclerosis, tumors develop in the cerebral subependymal region. Their exact nature has been the subject of debate. The cytology, histology and electron microscopy of a tumor which developed in a 16 year old male suffering from tuberose sclerosis are presented and the findings are discussed.

Bone marrow transplantation in lymphomatoid granulomatosis: Report of a case

Lymphomatoid granulomatosis is an unusual disorder histologically characterized by an angiocentric, angiodestructive mixed cellular infiltrate. The most frequent clinical manifestations are seen in the lungs, the skin, and the central nervous system. Progression to lymphoma may occur, particularly in patients who are anergic. The authors report the case of a boy who had had a splenectomy at 2 years of age for presumed Evans syndrome, and two episodes of pneumococcal meningitis at 5 and 10 years of age. At 14 years, he had severe respiratory compromise, and a lung biopsy specimen showed lymphomatoid granulomatosis. The liver and bone marrow also were affected. Improvement occurred with multiagent chemotherapy, but he had multiple relapses. A bone marrow transplant was performed using a human leukocyte antigen (HLA) identical mixed lymphocyte culture (MLC) nonreactive brother as the donor. He remains in remission more than 3 years post‐transplant. In addition, his abnormal immune function has improved.

Mycoplasma pneumonia associated with acute glomerulonephritis.

An 11-year-old girl who presented with pneumonia, pleural effusion, hematuria, and red blood cell casts is described. Mycoplasma pneumoniae complement fixation titers were elevated. The pneumonia resolved following therapy with tetracycline. Light microscopy of renal biopsy tissue revealed an acute glomerulonephritis; immunofluorescent studies showed deposits of IgG, C3 and mycoplasma antigen along the glomerular capillary walls and in the mesangium; subendothelial and subepithelial deposits were seen by electron microscopy. This is the first report of acute glomerulonephritis associated with M. pneumoniae infection with evidence of mycoplasma-induced immune complex nephritis.

Coexpression and accumulation of ubiquitin +1 and ZZ proteins in livers of children with alpha(1)-antitrypsin deficiency.

The ZZ variant of α1-antitrypsin deficiency (AATD) is well known to cause liver damage and cirrhosis in some affected children. Ubiquitin abnormality was recently shown to be significant in AATD in childhood cirrhosis. Molecular misreading (MM), defined as faulty transcription of genomic information from DNA into mRNA, as well as its translation into mutant proteins, has been documented in many pathologic processes where aggregation of abnormal proteins occurs. The misread protein, ubiquitin-B+1 (UBB+1), was recently identified in the hallmarks of various neurological disorders. The objective of this study was to determine whether MM of ubiquitin occurs in AATD. Twelve explanted liver specimens from AATD-affected children with cirrhosis were retrieved from archival sources, along with 10 control liver specimens obtained from autopsies of age-matched children with no clinical, gross anatomic, or histologic evidence of liver disease. Double immunofluorescence studies using rabbit polyclonal antibodies against UBB+1 and AAT were performed on consecutively sectioned tissue. UBB+1 immunoreactivity was colocalized with AAT in all cirrhotic AATD livers. The control livers were consistently negative. Ubiquitin MM is prominent in AATD-affected cirrhotic livers. This indicates that for children with AATD and cirrhosis, ubiquitin MM is a necessary cofactor to the aggregation of mutant ZZ isoform of AATD.