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Biomedical subjects

L R Margraf

Publications and source records attributed to L R Margraf.

28 records · Page 2Linked to original sources
PubMed1991

Morphometric analysis of the lung in bronchopulmonary dysplasia.

We studied lung development in children with or without bronchopulmonary dysplasia (BPD) using light microscopic morphometry and thick lung sections stained for elastic fibers. One lung was obtained at autopsy from each of eight patients with BPD (ages, 2 to 28 months) and six children (ages, 5 days to 51 months) who died without lung disease. Patients with BPD demonstrated severe somatic growth retardation and had reduced lung volumes with abnormal lobar volume proportions. In the central bronchi mean volume proportion of glands and smooth muscle was increased in BPD. Bronchiolar density was also increased, but it tended to normalize with advancing age. Mean bronchiolar diameter was slightly smaller in BPD, and bronchiolar smooth muscle hypertrophy was a constant histologic feature. The most striking change, however, was noted in alveolar structure and development. Total alveolar number was severely decreased in patients with BPD compared with that in control subjects, and there was little evidence of compensatory alveolar development with increasing age. Lung internal surface area was correspondingly reduced, and mean linear intercept was increased. Sections stained for elastic tissue demonstrated in the patients with BPD a simplified acinar structure with thickened, tortuous, and irregularly distributed alveolar elastic fibers. We conclude that in severe, fatal BPD there is marked impairment of lung development with alveolar hypoplasia and reduced internal surface area. In addition, bronchial and bronchiolar smooth muscle hypertrophy and bronchial gland hyperplasia may be important contributing factors to airflow limitation.

Body Height↗
PubMed1990

Surfactant-associated glycoproteins accumulate in alveolar cells and secretions during reparative stage of hyaline membrane disease.

Surfactant-associated (SA) glycoproteins are lung-specific proteins produced in the human lung by alveolar type II cells and Clara cells. The distribution of these proteins was studied immunohistochemically in lung tissue obtained postmortem from 12 stillborn fetuses and 49 infants with hyaline membrane disease (HMD). By 21 weeks of gestation, SA glycoproteins were detected in the fetal alveolar epithelium and within Clara cells. The staining increased in intensity and extent with advancing gestational age. Infants with HMD who survived less than 48 hours did not generally exhibit stainable material either within type II cells or secretions, but staining was often noted in Clara cells as well as focally beneath hyaline membranes. In infants surviving more than 48 hours, intense staining of hyaline membranes, alveolar secretions, proliferating alveolar type II cells, and Clara cells was evident. Immunoreactivity was intense in hypertrophic type II cells that formed a continuous alveolar epithelial lining in lungs with bronchopulmonary dysplasia. Included in the population of infants with HMD were 15 infants with pulmonary hypoplasia. The lungs of these infants showed minimal staining for SA glycoproteins regardless of postnatal survival time. The results provide an immunomorphologic basis for defining normal and abnormal lung maturation. They also indicate that enhanced SA glycoprotein production is a sustained response of regenerating and hypertrophic type II cells in premature infants.

Humans↗
PubMed1987

Progressive necrotizing myelopathy associated with leukemia: clinical, pathologic, and MRI correlation.

We describe a patient with progressive, irreversible, necrotizing myelopathy associated with myelomonocytic leukemia. The neuropathologic lesions consisted of diffuse necrosis, most pronounced in the cervical cord and affecting both the gray and white matter. These areas corresponded to areas of increased T2 on magnetic resonance imaging scans of the patient. We felt that there was no causal relationship of these lesions to any single antileukemic agent the patient received, and no other local or systemic causes were found to explain the lesions at necropsy. It is suggested that our case is an example of paraneoplastic necrotizing myelopathy. To our knowledge, this is the third case of necrotizing myelopathy associated with leukemia reported in the English medical literature, and the first one demonstrating usefulness of magnetic resonance imaging in diagnosis of necrotizing myelopathy.

Adolescent↗
PubMedDate not supplied

Cytomegalovirus and human herpesvirus 6, but not human papillomavirus, are present in neonatal giant cell hepatitis and extrahepatic biliary atresia.

The purpose of our study was to confirm reports of an association of human papillomavirus (HPV) with neonatal giant cell hepatitis (GCH) and biliary atresia (BA), and to expand these studies to include cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV6), and parvovirus B19 (PVB19). Frozen hepatic tissue was available for polymerase chain reaction (PCR) analysis in 19 cases of GCH or BA and 8 controls. Nested PCR to detect HPV types 6, 16, 18, and 33 was followed by 32P hybridization with generic probes. PCR followed by hybridization with a digoxigenin-labeled probe was used for all other viruses. HPV, EBV, and PVB19 were not detected in cases or controls. Two cases of GCH and 1 case of BA were PCR positive for CMV; controls were negative. HHV6 was detected in 6 cases: 2 GCH, 2 BA, and 2 controls. We conclude that HPV is not associated with GCH or BA. Detection of CMV in BA and GCH confirms other reports of this association. HHV6 requires further study to determine the significance of a positive PCR test in the livers of infants.

Biliary Atresia↗
PubMedDate not supplied

Synchronous wilms tumor and fibrolamellar hepatocellular carcinoma: report of a case.

Fibrolamellar hepatocellular carcinoma (FHCC) is a unique histologic variant of HCC that occurs in a younger subset of patients than classical HCC, and is associated with a better prognosis. Wilms tumor (WT) is a malignant embryonal neoplasm of the kidney and is one of the most common solid tumors of childhood, occurring at an estimated frequency of 1 in 8000 to 10,000 births. Although second malignant neoplasms (SMNs) following therapy for WTs have been reported in the liver, the coexistence of HCC and WT is extremely rare. We present the first report of a synchronous anaplastic WT and FHCC in a previously healthy 4-year-old girl. Despite the presence of focal immunohistochemical positivity for p53 in the WT, molecular analysis failed to reveal a germline or somatic p53 mutation, and was inconclusive in establishing a clonal relation between the two tumors.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Bcl-2 expression in Langerhans' cell histiocytosis.

Langerhans' cell histiocytosis (LCH) is an abnormal accumulation of dendritic histiocytes of unknown pathogenesis. It has recently been shown to be a clonal process. Bcl-2 is a proto-oncogene whose protein product is known to inhibit apoptosis. The overexpression of bcl-2 has been demonstrated in a number of neoplasms, presumably prolonging the survival of the neoplastic cells. We examined the expression of bcl-2 in normal Langerhans' cells in the skin and in LCH by immunohistochemistry for protein and in situ hybridization for mRNA to see if it could be implicated in the pathogenesis of this disorder. Additionally, we performed Southern analysis to determine if genomic rearrangement of the bcl-2 gene occurs in cases of LCH. Bcl-2 was not detected in normal skin Langerhans' cells. Eleven of thirteen cases of LCH demonstrated bcl-2 protein expression in the cytoplasm of the Langerhans' cells by immunohistochemistry, while 12 of 13 cases had evidence of bcl-2 mRNA by in situ hybridization. Southern analysis revealed a germline configuration of the bcl-2 gene in the five cases studied. These findings suggest that bcl-2 expression is present and up-regulated in pathologic Langerhans' cells, however, this overexpression does not appear to be due to genomic rearrangement.

Biomarkers↗
PubMedDate not supplied

Epstein-Barr virus lymphoproliferative disorder in children with leukemia: case report and review of the literature.

PURPOSE: The purpose of this study is to report a case of Epstein-Barr virus-related lymphoproliferative disorder (EBV-related LPD) in a child with leukemia and present a review of literature on the subject. PATIENTS AND METHODS: A 6-year-old boy with acute lymphoblastic leukemia (ALL) undergoing maintenance chemotherapy presented with fever, abdominal pain, and vomiting. Imaging studies revealed multiple mass lesions in the liver, kidneys, and lungs. Liver biopsy was obtained. Immunocytochemistry for T and B lymphocytes and in situ hybridization for evidence of latent EBV infection was performed. RESULTS: Hepatic portal tracts were infiltrated with lymphocytes, monocytes, eosinophils, and large atypical mononuclear cells. Both T and B lymphocytes were present, but the large atypical cells were of B origin and were positive for latent EBV infection. Chemotherapy was discontinued, and the patient was treated with intravenous gammaglobulin, interferon, and acyclovir. He had an excellent response and has been free of disease for 19 months. CONCLUSION: EBV-related LPD can complicate the course of patients with ALL in remission. The clinical findings and diagnosis in patients with ALL are similar to other immunocompromised patients. Withdrawal of chemotherapy and treatment with immune modulators should be strongly considered.

Child↗
PubMedDate not supplied

Successful prenatal therapy of thoracic lesions.

Improvements in prenatal imaging techniques now permit in utero treatment of potentially serious lesions. We describe three cases in which decompression of significant space-occupying thoracic lesions resulted in an excellent clinical outcome. The pregnancies were all carried to term after second or early third trimester intervention and resulted in infants with minimal respiratory distress. Cytologic and chemical analysis of the thoracic fluid aspirated in utero provided diagnostic and physiologic information.

Adult↗
PubMedDate not supplied

Pulmonary gastrin-releasing peptide expression in anencephaly.

Gastrin-releasing peptide (GRP) is a developmentally regulated bioactive peptide believed to function as a pulmonary growth factor. It is produced by pulmonary neuroendocrine cells, found within the conducting and respiratory epithelium, as isolated cells and in clusters known as neuroepithelial bodies (NEBs). Deficient GRP expression has been reported in pulmonary hypoplasia (PH) associated with oligohydramnios and diaphragmatic hernia. To assess further the role of GRP in maldeveloped lung we reviewed the postmortem records and histologic lung sections, stained with H&E and anti-GRP antiserum, from 11 infants with anencephaly and 11 age-matched controls. Cells immunoreactive for GRP were quantified (isolated versus NEBs) in airways and airspaces per mm2 for a standard area. PH was present in five anencephalic infants. There was no difference in the total number of GRP-positive cells, number of NEBs, size of NEBs, or number of GRP-positive cells in airways or alveoli in either group regardless of lung development. A greater proportion of the GRP-positive cells was present in the airways in anencephalic infants with PH (58%) compared with anencephalic infants without PH (40%) (P = .018). There were no differences when comparing these groups with control infants and no differences in the density of airways in each of these groups. We conclude that deficient GRP expression is not a feature of lung hypoplasia in anencephalic infants. The altered distribution of GRP-positive cells in anencephalic infants with PH may be a reflection of the structural abnormalities or accompanying altered cellular maturity.

Anencephaly↗