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  • 1
    ISSN: 1432-0851
    Keywords: Immunotoxins ; Methotrexate ; Immunoenzyme techniques ; Antibodies, monoclonal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Methotrexate (MTX) was coupled to the tumor-targeting monoclonal IgM, anti-SSEA-1 and the nontargeting myeloma IgM, MOPC 104E. At 24-h intervals following injection, drug deposition in MH-15 teratocarcinomas and in several normal tissues was followed by immunoperoxidase microscopy using the M16 monoclonal antibody to MTX. MTX-anti-SSEA-1 was deposited on the surface and in the interior of living tumor cells 24 h after injection; at 48 h and after, only low-level binding to necrotic tissue was found. There was no significant gradation in staining from the outside to the interior of the tumors. In tumors, the control MOPC 104E immunoconjugate was detectable only in necrotic tissue. Binding to SSEA-1-expressing normal tissues was undetectable, except for pericryptal fibroblasts in the small intestine. No significant pathology was found in normal tissues that are SSEA-1 positive. High levels of the immunoconjugate were detected in the liver, where MTX was found predominantly in Kupffer cells and possibly in hepatocytes; again, no significant morphological changes were associated with this retention. Thus tumor-associated antigens can be suitable targets for antibody-drug conjugates even when present in normal tissues and in large quantities, provided that the antigens in normal tissues are inaccessible. Moreover, deposition in viable tumor tissue can be assessed using monoclonal antibodies to methotrexate.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric cardiology 2 (1982), S. 63-65 
    ISSN: 1432-1971
    Keywords: Myocarditis ; Left ventricular aneurysm ; Cytomegalovirus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An infant with disseminated cytomegalovirus infection and apical aneurysm of the left ventricle died. At autopsy the coronary arteries were anatomically normal, but there was occlusion of the left anterior descending artery with an inflammatory lesion and corresponding organized thrombus. It seemed likely that cytomegalovirus infection acquired in utero may have induced an endothelial lesion, leading to thrombosis, occlusion, apical myocardial infarction, and eventual aneurysm formation.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0851
    Keywords: Photoimmunodiagnosis ; Monoclonal antibodies ; Fluorescence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Far-red-emitting cyanine fluorochromes have many properties desirable for in vivo imaging: absorption and emission at wavelengths where blood and tissue are relatively transparent, high quantum yields, and good solubility even at high molar ratios of fluorochrome to antibody. Potentially, conjugation by multiple linkages should minimize hydrolysis in vivo. We conjugated two tumor-targeting monoclonal antibodies: anti-SSEA-1 (IgM, κ) at ratios of 1.2–35 mol dye/mol antibody and 9.2.27 (IgG2a, κ) at 0.6–6 mol dye/mol antibody, using the cyanine fluorochromes Cy3.18, Cy5.18, and Cy5.5.18. Nude mice were inoculated using the SSEA-1-expressing MH-15 teratocarcinoma or the 9.2.27 antigen-expressing SK-MEL-2 melanoma to give tumors at several sites. Conjugated antibody was injected, and mice were imaged immediately after injection and at appropriate intervals thereafter using a standard camera lens, dissecting microscope, or endoscopes. Images were acquired using either an image-intensified video camera or cooled CCD cameras. Immediately after injection, major blood vessels and the heart, liver, and kidneys were readily visualized. After 1 day, tumor-targeting antibody conjugates were concentrated in tumors and there was little circulating conjugate; however, the bladder and kidneys were still visible. Tumors labeled by specific antibody were the most fluorescent tissues at 2 days after injection, but non-specific antibody conjugates did not concentrate in the tumors. The small intestine was weakly visualized by both specific and non-specific antibody conjugates. These data support the possibility of visualizing tumor metastasis by optical means, including currently available endoscopes.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0851
    Keywords: Key words Photoimmunodiagnosis ; Monoclonal antibodies ; Fluorescence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Far-red-emitting cyanine fluorochromes have many properties desirable for in vivo imaging: absorption and emission at wavelengths where blood and tissue are relatively transparent, high quantum yields, and good solubility even at high molar ratios of fluorochrome to antibody. Potentially, conjugation by multiple linkages should minimize hydrolysis in vivo. We conjugated two tumor-targeting monoclonal antibodies: anti-SSEA-1 (IgM, κ) at ratios of 1.2 – 35 mol dye/mol antibody and 9.2.27 (IgG2a, κ) at 0.6 – 6 mol dye/mol antibody, using the cyanine fluorochromes Cy3.18, Cy5.18, and Cy5.5.18. Nude mice were inoculated using the SSEA-1-expressing MH-15 teratocarcinoma or the 9.2.27 antigen-expressing SK-MEL-2 melanoma to give tumors at several sites. Conjugated antibody was injected, and mice were imaged immediately after injection and at appropriate intervals thereafter using a standard camera lens, dissecting microscope, or endoscopes. Images were acquired using either an image-intensified video camera or cooled CCD cameras. Immediately after injection, major blood vessels and the heart, liver, and kidneys were readily visualized. After 1 day, tumor-targeting antibody conjugates were concentrated in tumors and there was little circulating conjugate; however, the bladder and kidneys were still visible. Tumors labeled by specific antibody were the most fluorescent tissues at 2 days after injection, but non-specific antibody conjugates did not concentrate in the tumors. The small intestine was weakly visualized by both specific and non-specific antibody conjugates. These data support the possibility of visualizing tumor metastasis by optical means, including currently available endoscopes.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric and developmental pathology 1 (1998), S. 102-117 
    ISSN: 1615-5742
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric and developmental pathology 2 (1999), S. 360-366 
    ISSN: 1615-5742
    Keywords: Key words: hemophagocytic lymphohistiocytosis, hepatic failure, neonatal hemochromatosis, serum ferritin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: ABSTRACT Two patients with hemophagocytic lymphohistiocytosis who presented with acute liver failure are reported. Both presented with fever, hepatosplenomegaly, markedly elevated liver function tests, abnormal coagulation profiles, and an increase in serum ferritin. Both infants were diagnosed with neonatal hemochromatosis based on a clinical picture of hepatic insufficiency with hyperferritinemia and were referred for liver transplantation. The first patient died of liver failure and septicemia before transplantation. Review of autopsy material revealed a hepatitis-like pattern and extensive infiltration of liver and other organs including bone marrow by histiocytes, some of which were hemophagocytic. The second patient underwent liver transplantation but died 44 days thereafter from progressive hemophagocytic lymphohistiocytosis. Examination of the resected liver demonstrated a hepatitis-like pattern, proliferation of histiocytes, and hemophagocytosis, and the bone marrow revealed hemophagocytic histiocytosis. Hemophagocytosis recurred in the allograft. Hepatic manifestations are common in hemophagocytic lymphohistiocytosis and overt hepatic failure may occur, but initial presentation as fulminant hepatic failure is not well recognized. Elevated serum ferritin can make the distinction from neonatal hemochromatosis and other forms of neonatal liver failure difficult. Hemophagocytic lymphohistiocytosis should be considered in the differential diagnosis of neonatal liver disease, especially when it is accompanied by cytopenias.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric and developmental pathology 2 (1999), S. 588-596 
    ISSN: 1615-5742
    Keywords: Key words: acetylcholinesterase, aganglionosis, Hirschsprung disease, rectal biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: ABSTRACT Diagnostic pathologists remain uncomfortable with the diagnosis of Hirschsprung disease (HD) via rectal (mucosal/submucosal) biopsy and with performance and interpretation of the associated acetylcholinesterase (AChE) assay. This report details the different diagnostic approaches taken by four major pediatric institutions—Children's Hospital, Columbus, OH; Children's Hospital Medical Center, Cincinnati, OH; Children's Hospital, Pittsburgh, PA; Children's Hospital, Los Angeles, CA—in confirming or excluding the presence of HD. The Columbus approach emphasizes serial morphologic examination of rectal biopsies, while Cincinnati emphasizes the primary diagnostic utility of the AChE stain. Pittsburgh and Los Angeles emphasize a detailed gross and microscopic analysis of rectal biopsies to detect both conventional HD and its more rare subtypes. The diagnostic approaches of these four institutions can be used on a complementary basis to the advantage of the general diagnostic pathologist, especially in HD cases with subtle clinical presentations. The need for careful and continual communication between the clinician and pathologist in diagnosing or excluding the presence of HD is imperative.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric and developmental pathology 1 (1998), S. 216-221 
    ISSN: 1615-5742
    Keywords: Key words: dendritic cells, fascin, histiocytes, juvenile xanthogranuloma, p55 protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: ABSTRACT This is a descriptive screening of 46 examples of childhood histiocytic lesions and some of their look-alikes using a monoclonal antibody, p55, to fascin. Fascin, an actin-bundling protein, identifies dendritic cells in the blood and in tissues. Our aim was to test the diagnostic utility of the antibody in various lesions at different sites and to see whether the staining patterns give insight into the cell types involved. Fascin intensely stained the cells of juvenile xanthogranulomas (JXG), Rosai-Dorfman lesions, and soft tissue dendrocytomas. Normal Langerhans' cells and the cells of Langerhans' cell histiocytosis were unreactive. Their lack of fascin staining may be relevant to fascin being maturation as well as lineage related. Epithelioid and palisading granulomas were unstained, though an example of Kikuchi lymphadenitis had large numbers of dendritic-type cells that stained strongly. A reticulohistiocytoma of the skin was also unstained and look-alike lesions, Spitz nevi, and mast cell lesions did not stain. Two of three large-cell lymphomas (both CD30+) also had fascin reactivity. Even though fascin is not specific to dendritic cells, staining other cell types as well (false positive), and not entirely sensitive, dendritic cells such as tissue Langerhans' cells are unstained (false negative), there seems to be a consistency of staining in childhood histiocytic lesions. This may be of diagnostic use when read in the context of the tissue differential diagnosis. Whether fascin can serve as a marker for the dendritic cell lineage, or at least for some phases of dendritic cell lifecycle, is not answered by this survey.
    Type of Medium: Electronic Resource
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