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Biomedical subjects

E Kaiserling

Publications and source records attributed to E Kaiserling.

At least 37 records · Page 2Linked to original sources

Newly-formed lymph nodes in the submucosa in chronic inflammatory bowel disease.

BACKGROUND AND AIMS: Routine diagnostic work revealed cell aggregates reminiscent of lymph nodes in the bowel submucosa in occasional cases of chronic inflammatory bowel disease. We therefore investigated whether they fulfill criteria for classification as lymph nodes. METHODS: Colon with terminal ileum from a patient with florid Crohn's disease and a colectomy specimen from a patient with ulcerative colitis were investigated. Sections were immunostained with antibodies that recognize endothelial and sinus-lining cells, immune-accessory cells, and lymphoid cells. RESULTS: Circumscribed collections of cells that fulfill all the major criteria for classification as lymph nodes were found in the large and small bowel. They had marginal and intermediate sinuses (positive for BMA 120, CD34, CD31, X-11, and von Willebrand's factor), afferent lymph vessels, T- and B-regions, and a capsule. Small collections composed predominantly of B cells that had only a marginal sinus were also occasionally observed. CONCLUSION: Secondary mucosa-associated lymphoid tissue, typically seen as follicular lymphoid hyperplasia, also appears to occur as secondary submucosal lymph nodes. This phenomenon seems inconsistent with the notion that lymph nodes do not develop after birth. We have also noted secondary development of lymph nodes in lymphangioma and lymphangioleiomyomatosis. It is possible that local lymph vessel proliferation, possibly with chronic lymphedema of the tissue involved, is an important prerequisite for lymph node neogenesis.

Adult↗

Central nervous system Hodgkin's lymphoma without systemic manifestation: case report and review of the literature.

A 66-year-old woman treated for ocular myasthenia gravis with azathioprine for 12 years presented with a left fronto-parietal mass. Histology revealed primary Hodgkin's lymphoma of the central nervous system with CD30, Epstein-Barr virus (EBV) latent membrane protein and CD20-positive, CD45 (LCA)-negative Reed-Sternberg cells surrounded by T cells. Moreover, EBV-encoded RNA-1 (EBER-1) sequences and a monoclonal rearrangement of the immunoglobulin heavy chain CDR2 locus were detected.

Aged↗

Biodegradable nanoparticles for oral delivery of peptides: is there a role for polymers to affect mucosal uptake?

Numerous authors have demonstrated uptake of micro- and nanospheres, consisting of natural or synthetic polymeric materials from the gastrointestinal tract over the past two decades. The exploitation of particulate carrier systems for the delivery of peptides and other hydrophilic macromolecules via the oral route remains a challenging task due to morphological and physiological absorption barriers in the gastrointestinal tract. This review examines recent progress in the field of nanoparticle uptake from this site of administration. Since most studies have been performed with poly(styrene) particles of different sizes relatively little is known about both the effect of physicochemical particle properties critical for absorption after peroral application, and the mechanisms of gastrointestinal particle uptake. Apart from particle size, type and composition of the polymers used for micro- or nanoencapsulation are crucial for an uptake and transport across mucosal barriers. Factors such as particle surface charge and hydrophilic/hydrophobic balance of these polymeric materials have not been investigated systematically since adjustment of these particle properties is almost impossible without synthetic modification of the polymers. The current findings will be reviewed and compared to those obtained with nanoparticles consisting of a novel class of charged comb polyesters, poly(2-sulfobutyl-vinyl alcohol)-graft-poly(D,L-lactic-co-glycolic acid), SB-PVAL-g-PLGA, allowing adjustment of physicochemical nanoparticle properties with a single class of polymers.

Administration, Oral↗

Melanocytes in nevi and melanomas synthesize basement membrane and basement membrane-like material. An immunohistochemical and electron microscopic study including immunoelectron microscopy.

Light microscopic studies have shown that nevus cell nests and melanoma nests are surrounded by basement membrane (BM) material containing type IV collagen and laminin. This study confirms this by electron microscopy and relates it to proteins which interact with the basement membrane. Nevi except for dysplastic and Spitz nevi, malignant melanomas, and melanoma metastases were studied by immunohistopathology, routine electron microscopy (EM), and immunoelectron microscopy. The lesions were incubated with monoclonal antibody (moAb) against type IV collagen, laminin, and the integrin alpha6 and studied by light microscopy. In addition, melanomas were studied by immuno-EM after incubation with a moAb against matrix metalloproteinase-2 (MMP-2). Nevus cell nests and melanoma nests are surrounded by BM material containing type IV collagen and laminin by immuno-EM. The BM material various in thickness and is amorphous. Type IV collagen, laminin, and MMP-2 are synthesized by melanoma cells as well as adjacent fibroblasts. Destruction or loss of the BM is not mandatory for melanoma invasion or even metastasis. Possibly the BM material is a protective wall for melanoma cells. Interactions between melanocytes and the extracellular matrix of which the BM is a part, can be traced back to the migration of melanocytes from the neural crest.

Antibodies, Monoclonal↗

Acute lymphoblastic leukaemia: correlation between morphological/immunohistochemical and molecular biological findings in bone marrow biopsy specimens.

BACKGROUND: Although numerous antibodies suitable for use on paraffin wax embedded sections are available for the subtyping of acute leukaemia (acute myelogenous leukaemia (AML) and acute lymphoblastic leukaemia (ALL)) in bone marrow biopsy sections, unequivocal identification of the cell line involved is sometimes impossible. METHODS: Forty eight formalin fixed, paraffin wax embedded bone marrow biopsy specimens that had been decalcified in EDTA were investigated, including 42 thought to exhibit ALL on the basis of bone marrow smears. Five specimens exhibited AML and one biphenotypic leukaemia, as diagnosed immunohistochemically in bone marrow biopsies. Immunostaining was performed with antibodies against relatively specific B and T cell antigens. The blasts were investigated for rearrangements of the immunoglobulin heavy chain (IgH) and the T cell antigen receptor (TCR) genes. RESULTS: Amplifiable DNA was obtained from all 48 specimens. An IgH gene rearrangement was detected in 20 of 23 c-ALL specimens. Four of seven T cell ALL (T-ALL) specimens had a TCR-gamma gene rearrangement, and the one B cell ALL (B-ALL) specimen exhibited a clonal IgH gene. Three of four cases of unclassifiable ALL could be assigned to the B cell lineage on the basis of gene rearrangement analysis. Seven cases originally diagnosed in smears as ALL were rediagnosed as AML (n = 5) or biphenotypic leukaemia (n = 2) because of immunohistochemical reactivity for myeloperoxidase or lysozyme. Two of these AML cases and two of three cases of biphenotypic leukaemia exhibited a monoclonal IgH gene rearrangement. CONCLUSIONS: Acute leukaemia can be subtyped in bone marrow sections with a limited panel of antibodies suitable for use on paraffin wax embedded sections (against CD3, CD10, CD20, CD79a, myeloperoxidase, and lysozyme). In patients with ALL and a diagnostically equivocal immunophenotype, gene rearrangement analysis might indicate whether the B or T cell lineage is involved.

B-Lymphocytes↗

Intracranial inflammatory tumors: a survey of their various etiologies by presentation of 5 cases.

Due to similar clinical and neuroradiological features, intracranial inflammatory tumors (IITs) are frequently misdiagnosed as brain neoplasms, from which they notably differ in respect to therapy and prognosis. In this article, five cases of such tumors are presented. Three of the patients with brain tumors (cases 3, 4 and 5) presented a history of 'pararheumatic' syndromes but no diagnosis of defined immunopathies. On the basis of radiological findings, all processes were classified as genuine brain neoplasms, but histology showed reactive inflammatory features. The possible etiologies of these 'tumors' are discussed on the basis of all clinical and histological data of the patients. The spectrum of diseases potentially leading to the manifestation of an IIT is reviewed. Additionally, the presentation of case 5, who developed a highly malignant B-cell-lymphoma 6 months after the removal of an IIT without any histological signs of atypia, shows that this differential diagnosis always has to be kept in mind.

Adult↗

Small epithelial cells in extrahepatic biliary atresia: electron microscopic and immunoelectron microscopic findings suggest a close relationship to liver progenitor cells.

AIMS: It is still unclear whether hepatic stem cells that give rise to both biliary epithelial cells and hepatocytes exist in the human liver. The aim of this study was to investigate whether cells with ultrastructural and immunophenotypical features similar to those of the oval cells of rodents or the small epithelial cells (SEC) described recently in hepatoblastoma, i.e. putative hepatic progenitor cells, are found in the liver of patients with extrahepatic biliary atresia. METHODS AND RESULTS: Liver biopsies from 10 infants with extrahepatic biliary atresia were investigated by transmission electron microscopy. Single and double immunolabelling for cytokeratin 7, a marker of biliary differentiation, and albumin, a marker of hepatocytic differentiation, was investigated by immunoelectron microscopy. Electron microscopy revealed SEC that were ultrastructurally similar to the oval cells and coexpressed albumin and cytokeratin 7. The SEC exhibited a spectrum of differentiation that, in addition to relatively undifferentiated cells, included cells that exhibited morphological and immunophenotypical signs of differentiation towards biliary epithelial cells and hepatocytes. CONCLUSIONS: The findings demonstrate that SEC with morphological and immunophenotypical features of the oval cells of rodents and the SEC described in hepatoblastoma are found in the liver of patients with extrahepatic biliary atresia. The data further support the hypothesis that the SEC represent possible candidates for hepatic progenitor cells.

Albumins↗

Parturition at term: parallel increases in interleukin-8 and proteinase concentrations and neutrophil count in the lower uterine segment.

A relationship was sought between the tissue concentrations of interleukin (IL)-8, matrix metalloproteinase (MMP)-8 and MMP-9, and the numbers of the various leukocytes infiltrating the lower uterine segment stroma during parturition. Biopsy specimens of the lower uterine segment were obtained from 63 women undergoing Caesarean section at various stages of cervical dilatation at term. The concentrations of IL-8, MMP-8 and MMP-9 were determined with enzyme-linked immunosorbent assays, and the leukocytes were quantified immunohistochemically. The median IL-8 concentration (pg/mg total protein) rose significantly from 17.2 at < 2 cm dilatation, to 26.5 at 2 to < 4 cm dilatation, and 1954.0 at 4-6 cm dilatation, and remained at approximately this concentration at > 6 cm dilatation. The median MMP-8 concentration (ng/mg total protein) increased significantly from 32.2 at < 2 cm dilatation to 114.2 at > 6 cm dilatation. The median MMP-9 concentration (ng/mg total protein) rose significantly from 15.4 at < 2 cm dilatation to 102.1 at > 6 cm dilatation. The number of neutrophils was significantly higher at 4-6 cm and > 6 cm dilatation than at > 2 cm, reaching maximum values at > 6 cm dilatation. The findings in this study support the hypothesis that IL-8-induced infiltration of the cervical stroma by neutrophils and subsequent release of proteinases may play a key role in parturition.

Adult↗

Granulomatous mycosis fungoides: report of a case with some histopathologic features of granulomatous slack skin.

We describe a case of granulomatous mycosis fungoides, tumor stage, mimicking sarcoidosis in an 82-year-old man with a 2-year history of skin disease. The final diagnosis was established after one of seven biopsy specimens showed a nongranulomatous histologic picture of patch-stage mycosis fungoides. Monoclonality was proven for the lymphocytic population by T-cell-receptor rearrangement studies. The unusually extensive granulomatous inflammation with huge giant cells surrounded by CD1a-positive cells in the other six biopsy specimens was suggestive of the histopathology of granulomatous slack skin, another rare granulomatous cutaneous T-cell lymphoma. Because both a clinical and histologic overlap between granulomatous mycosis fungoides and granulomatous slack skin have been reported in the literature, we conclude that they may belong to the spectrum of a single disease.

Aged↗

Reactive and neoplastic lymphocytes in human bone marrow: morphological, immunohistological, and molecular biological investigations on biopsy specimens.

BACKGROUND: Slight, diffuse or focal lymphocyte proliferation is relatively common in bone marrow biopsy specimens. It may be impossible to determine whether this represents a reactive lymphocytosis or low grade non-Hodgkin lymphoma (NHL) on the basis of routine investigations alone. AIM: To investigate the supplementary use of molecular biological techniques in this situation. METHODS: 529 formalin fixed, paraffin embedded bone marrow biopsy specimens from the iliac crest were subjected to histological and immunohistochemical staining to determine the number and nature of the lymphocytes present. The cases were divided into three groups according to the lymphocyte count: normal (< 10% of nucleated bone marrow cells), slightly increased (10-30%), and markedly increased (> 30%). All of the last group could be diagnosed as NHL from the morphological findings alone. The clonality of rearrangements of the IgH and TCR gamma genes was investigated by polymerase chain reaction (PCR). RESULTS: Monoclonality was observed in 7.5% of the 372 cases with a normal lymphocyte count, in 50% of the cases with a modest increase in lymphocyte numbers (suggesting a diagnosis of low grade NHL not detected by immunostaining), and in 77% of the cases with markedly increased lymphocyte numbers. CONCLUSIONS: If PCR is used in addition to the immunohistochemical investigation of bone marrow biopsies, considerably more cases of NHL can be identified, making this of particular use in staging and detection of recurrences.

Bone Marrow Cells↗

Immunophenotyping of acute lymphoblastic leukaemia in routinely processed bone marrow biopsy specimens.

AIMS: To assess the value of immunophenotyping of acute lymphoblastic leukaemia (ALL) in routinely processed bone marrow trephine biopsy specimens and to establish a minimum panel of antibodies to assess lymphoid lineage and enable differentiation from acute myeloid leukaemia. METHODS: 45 routinely processed bone marrow biopsy specimens (formalin fixed, paraffin embedded and mildly decalcified in EDTA) reported to contain leukaemic infiltrates on the basis of cytomorphological and enzyme-cytochemical analysis of bone marrow smears (22 c-ALL, 11 T-ALL, 2 B-ALL, 10 u-ALL (unclassified)) were immunostained by the ABC method with a broad panel of 26 antibodies against various haemopoietic antigens. RESULTS: Staining with antibodies directed against myeloperoxidase and lysozyme showed that seven cases were either biphenotypic or mixed leukaemias (2), or of myelogenous origin (acute myeloid leukaemia (AML)-M1 (2); AML-M4 (2); AML-M5a (1)). Five of these seven cases had been diagnosed initially as u-ALL. Three further cases with no compact leukaemic infiltrates were excluded. ALL was confirmed in the remaining 35 cases. Because of revised diagnoses, the total numbers of ALL subtypes changed (23 c-ALL, 8 T-ALL, 2 B-ALL, 2 u-ALL). Immunostaining of more than 10% of blast cells in at least one case was found with 19 of the 26 antibodies. The most sensitive lineage specific antibodies for diagnosis were found to be anti-CD10 for c-ALL (22/23) and beta F1 for T-ALL (6/8). Expression of aberrant antigens was fairly common--for example, 7/23 cases of c-ALL stained with antibodies against T cell associated antigens. CONCLUSIONS: Immunohistochemical investigation of routinely processed bone marrow biopsy specimens enables reliable detection of ALL subtypes c-ALL and T-ALL. A minimum panel of antibodies, against TdT, CD34, myeloperoxidase, lysozyme, CD10, CD79a, and CD20, and the antibody beta F1, is proposed for the immunophenotyping of acute leukaemia.

Antigens, Neoplasm↗

Granulosa cell tumor of the ovary. Immunohistochemical evidence of low proliferative activity and virtual absence of mutation of the p53 tumor-suppressor gene.

BACKGROUND AND METHODS: Because the use of immunohistochemistry in the diagnosis of granulosa cell tumor (GCT) has not been fully explored, routinely processed (formalin-fixed, paraffin-embedded) tissue from 11 GCT, adult type, was investigated immunohistochemically (ABC method) with a broad spectrum of antibodies against various markers, including p53 and Ki-67. All of the tumors exhibited typical morphology, were limited to the ovary (stage I), and 7 cases followed a benign clinical course. RESULTS: All the tumors exhibited strong expression of vimentin, but most other antigens (including smooth muscle actin) were expressed infrequently by a minority of tumor cells or not at all. Tumor cells in 9 GCT expressed inhibin A. All the tumors exhibited very low proliferative activity, fewer than 10% of the tumor cell nuclei being stained by the antibody MIB-1 (Ki-67 antigen). The antibody D07 revealed marked overexpression of p53 protein in only one tumor. Clinical outcome was not found to be related to immunophenotypic differences. CONCLUSIONS: The diagnosis of GCT should be based primarily on the typical morphology revealed by conventional stains, but additional immunohistochemical staining with a small panel of selected antibodies (for example, against keratin, vimentin, and inhibin A) may be helpful in a few cases. The very low proliferative activity and the lack of overexpression of p53 protein are consistent with the benign clinical behavior of the majority of GCT.

Actins↗

Frequent expression of haemopoietic and non-haemopoietic antigens by reactive plasma cells: an immunohistochemical study using formalin-fixed, paraffin-embedded tissue.

Unlike other B cells, plasma cells (PC) react with only a few antibodies against haemopoietic antigens. We investigated 36 specimens exhibiting a reactive increase in PC numbers (i.e. plasmacytosis, PC hyperplasia) with a broad panel of antibodies suitable for use on formalin-fixed, paraffin-embedded tissue, and compared the findings with those obtained in 51 cases of multiple myeloma (plasmacytoma). Regardless of the immunostaining pattern for immunoglobulin light and heavy chains, reactive PC reacted with at least two and at most six of seventeen antibodies detecting haemopoietic antigens [Ber-H2/CD30 (91%), anti-leucocyte common antigen (LCA)/CD45 (86%), KP1/CD68 (64%), MB2 (57%), 4KB5/CD45RA (37%), DF-T1/CD43 (28%), UCHL1/CD45RO (20%), L26/CD20 (17%), MT2 (14%) and Mac387 (8%)], and with at least one and at most four of six antibodies against non-haemopoietic antigens [anti-epithelial membrane antigen (EMA) (94%), anti-vimentin (77%), anti-pan-cytokeratin/KL1 (74%), BMA120 (51%) and HMB45 (14%)]. Five antibodies stained reactive PC significantly more often than neoplastic PC: Ber-H2/CD30 (p < or = 0.0000), KP1/CD68 (p < or = 0.0000), anti-LCA/CD45 (p < or = 0.0000), anti-EMA (p < or = 0.0339) and anti-pancytokeratin/KL1 (p < or = 0.0000). The more frequent and more heterogeneous expression of antigens by reactive PC suggests that the aberrant immunoreactivity of neoplastic PC in plasmacytoma is not due to the process of malignant transformation in an early step of B-cell differentiation, but could reflect the heterogeneity of antigen expression by normal PC.

Fixatives↗

Differential diagnosis of metastases in bone scans: chemotherapy induced bone necrosis.

AIM: Influenced by the incorrect diagnosis of a bone metastasis caused by bone necrosis we evaluated reasons and frequency of bone necrosis in patients referred for bone scanning in follow-up of tumors. METHODS: Bone scans performed within two years on patients with primary bone tumors or tumors metastatic to bone were reviewed in respect to the final diagnosis bone necrosis. RESULTS: We found the cases of three young patients who presented the appearance of hot spots on bone scintigrams which were finally diagnosed as bone necrosis. In two cases the diagnosis was based on histological findings, in one case the diagnosis was made evident by follow-up. All the three patients had been treated by chemotherapy and presented no other reason for the development of bone necrosis. Enhanced tracer uptake in all sites decreased within eight weeks up to two years without therapy. CONCLUSION: Single and multiple hot spots after chemotherapy may be originated by bone necrosis but mimicry metastases.

Adolescent↗