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Biomedical subjects

M van de Rijn

Publications and source records attributed to M van de Rijn.

At least 55 records · Page 3Linked to original sources
PubMed1995

Virus-associated hemophagocytic syndrome characterized by clonal Epstein-Barr virus genome.

Virus-associated hemophagocytic syndromes are a heterogeneous group of disorders in which viral infection is associated with a proliferation of hemophagocytic histiocytes throughout the reticuloendothelial system. The authors report the case of a 24-year-old Vietnamese male who developed a hemophagocytic syndrome associated with Epstein-Barr virus (EBV) and who died following a rapidly progressive course. A proliferation of reactive-appearing lymphoid cells was associated with an extensive proliferation of erythrophagocytic histiocytes. Immunophenotypically, the lymphoid infiltrate consisted of CD56+ natural killer cells, predominantly CD8+ T-cells and rare B-cells (CD20+). Double-label immunohistochemical studies showed CD3+ T-cells and CD56+ natural killer cells to be distinct cell populations. Combined immunohistochemical-in situ hybridization studies localized EBV to CD43+, CD3-, CD68-, lymphoid-appearing cells, indicating the presence of EBV within natural killer cells. Southern hybridization analysis of EBV genomic termini revealed clonal EBV genome. However, there was no detectable immunoglobulin or T-cell receptor gene rearrangements. The findings indicate that this case of hemophagocytic syndrome represents a clonal proliferation of natural killer cells containing EBV and highlights the importance of the analysis of EBV genomic termini for determination of clonality in EBV-associated proliferations. It is possible that other cases of fulminant EBV-associated hemophagocytic syndromes represent clonal natural killer cell proliferations.

Adult↗
PubMed1995

Clonal VDJ recombination of the immunoglobulin heavy chain gene by PCR in classical Hodgkin's disease.

Although Hodgkin's disease (HD) has been a subject of much investigation, fundamental questions remain unanswered regarding its lineage and clonality. The authors used a polymerase chain reaction (PCR) technique to investigate whether clonal Variable-Diversity-Joining recombination of the immunoglobulin heavy (IgH) chain gene, a phenomenon that characterizes clonal B-cell proliferations, exists in nodular sclerosing (NSHD) and mixed cellularity (MCHD) Hodgkin's disease (so-called "classical" Hodgkin's disease). The isolation of DNA from paraffin-embedded tissue sections allowed for direct correlation of PCR results with the cell populations that were analyzed. Thirty-two cases were studied. These included 12 cases in which the Reed-Sternberg (RS) cells expressed the B-cell antigen, CD20, and 10 cases that were classified as syncytial variant of NSHD (3 CD20+, 7 B-cell antigen negative). Overall, clonal patterns of VDJ PCR products were found in 14 of 32 (44%) cases. These clonal patterns were identified in 7 of 12 (58%) cases of CD20+ classical HD and in 7 of 20 (35%) cases of B-antigen-negative classical HD. Clonal patterns were found in 3 of 10 cases of syncytial variant of NSHD, including 2 of 3 (67%) CD20+ cases and 1 of 7 (14%) B-cell antigen-negative cases. The results of this study provide support that a subset of HD represents a clonal B-cell neoplasm, and indicate that clonal IgH VDJ sequences are more frequently found in CD20+ HD.

Antigens, CD20↗
PubMed1995

Immunosuppression-associated lymphoproliferative disorders in rheumatic patients.

The association between rheumatic disease and the occurrence of hematolymphoid neoplasms has been a subject of investigation for many years. Recently, we and others have reported the development in rheumatic patients of lymphoproliferative disorders that are similar to those occurring in patients with known immunocompromised states. The lymphoid neoplasms that develop in patients with immunosuppression are characterized by several features including the presence of EBV genome in the neoplastic cells. The fact that lymphomas with features of those occurring in immunosuppressed patients can occur in patients with rheumatic disease suggests that immune system impairment secondary to the rheumatic disease, the treatment given for the rheumatic disease, or to a combination of these factors, might play a role in the development of lymphoma in these patients. This review will first describe the characteristics of lymphoproliferative disorders that occur in patients with known immunocompromised states. It will then review general aspects of lymphomas in rheumatic patients with a focus on more recent reports that have described the development of immunosuppression-associated lymphoproliferative disorders in rheumatic patients. Studies that investigate the relative contribution of the rheumatic disease versus therapy for rheumatic disease in the development of lymphoma in this patient group are still needed.

Adult↗
PubMed1995

bcl-2 expression in primary malignancies of the skin.

BACKGROUND AND DESIGN: Basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM) are the three most common malignant neoplasms that arise in the skin. Deregulation of oncogene function not infrequently leads to an increased rate of cellular proliferation. However, the expansion of malignant cells can also occur if programmed cell death is inhibited. The oncogene bcl-2 participates in the regulation of apoptosis (programmed cell death). In view of this, we determined the presence and possible role of bcl-2 in primary cutaneous malignancies. Routine paraffin sections of formalin-fixed BCCs, SCCs, MMs (primary and metastatic), actinic keratoses, and SCCs in situ were labeled with anti-bcl-2 monoclonal antibody using a biotin-avidin-immunoperoxidase procedure. RESULTS: Twenty-three BCCs were examined and all expressed cytoplasmic bcl-2. Two of 20 SCCs were positive. One of these had patchy, diffuse staining, and the other stained in only small foci. None of eight SCCs in situ and none of eight actinic keratoses expressed bcl-2. Sixteen of 18 MMs expressed bcl-2. CONCLUSIONS: The bcl-2 gene product has been found to inhibit apoptosis. Our preliminary results suggest that the expression of bcl-2 is present quite consistently in BCCs and MMs, but not in SCCs or precursor lesions. The expression (or lack thereof) of bcl-2 may reflect the difference in the regulation of cell turnover between these tumors, or histogenetic differences.

Basal Cell Carcinoma↗
PubMed1995

bcl-2 expression in melanocytic nevi. Insights into the biology of dermal maturation.

BACKGROUND AND DESIGN: Recently, a new category of oncogenes has been discovered that regulate programmed cell death. The bcl-2 oncogene has been found to inhibit cellular death without affecting cellular proliferation. In the skin, bcl-2 expression is limited to cells along the basal cell layer. However, we also noticed that resting melanocytes appeared to express bcl-2. We examined the expression of bcl-2 and its possible role in the biology of benign melanocytic proliferations. Routine paraffin sections of formalin-fixed tissue were labeled with anti-bcl-2 monoclonal antibody, and expression of bcl-2 was detected by a biotin-avidin-immunoperoxidase procedure. RESULTS: We examined 13 congenital, 11 acquired, and six atypical or dysplastic nevi for expression of bcl-2. Expression of bcl-2 was observed in 11 of 13 congenital nevi. All 11 acquired nevi and 6 nevi with architectural disarray and cytologic atypia expressed bcl-2. Both junctional and intradermal melanocytes expressed bcl-2 in a perinuclear and cytoplasmic pattern. Within neurotized areas, bcl-2 became significantly weaker and totally absent. CONCLUSIONS: In mature tissues, bcl-2 expression is quite limited. It appears to be restricted to pluripotential stem cells that serve as a reservoir for tissue that is constantly undergoing renewal, such as the hematopoietic cells and the intestinal mucosa. In the skin, bcl-2 expression has been previously reported to be limited to the epidermal basal cell layer and proliferation zones. Our results indicate that resting melanocytes and melanocytic nevi regularly express bcl-2.

Aging↗
PubMed1994

Epstein-Barr virus-associated natural killer-large granular lymphocyte leukemia.

We describe the first case of an Epstein-Barr virus (EBV)-associated natural killer-large granular lymphocyte (NK-LGL) leukemia in the United States to the best of our knowledge. A 29-year-old woman of Japanese descent developed EBV infection after a blood transfusion as indicated by a rise in serum antibody titers. Peripheral blood and bone marrow aspirate smears demonstrated increased LGLs. Flow cytometry showed that these cells expressed NK-associated surface antigens. Cytogenetic analysis of the bone marrow aspirate showed two distinct but related clones with multiple copies of a modified 7 marker chromosome. Death followed colonic perforation. Findings at necropsy included bone marrow lymphocytosis and erythrophagocytosis, a mononucleosis-like lymphadenitis, atypical hepatitis with a mixed, predominantly T-cell infiltrate, interstitial pneumonitis, and multiorgan system vasculitis with perforation of the transverse colon. Epstein-Barr virus transcripts were identified in lymphocytes infiltrating liver and peripheral nerve by in situ hybridization. In addition, Southern blot analyses showed monoclonal bands superimposed on oligoclonal ladders of EBV termini in liver and lymph node. The identical episomal form of EBV was found in the bone marrow, lymph node, and liver. No immunoglobulin (Ig), T-cell receptor beta, or T-cell receptor gamma chain gene rearrangements were identified. These studies support the hypothesis that the LGL population was a neoplastic EBV-related clonal proliferation of NK cells.

Adult↗
PubMed1994

CD34 expression by gastrointestinal tract stromal tumors.

Gastrointestinal stromal tumors (GISTs) are neoplasms arising in the wall of the gastrointestinal tract that frequently show evidence of smooth muscle differentiation, either by their appearance alone or by immunohistology. A significant number of these neoplasms fail to react with any markers of muscle differentiation, however. A subset of these neoplasms have epithelioid features, and the presence of these features can give rise to confusion with other neoplasms, such as carcinomas and melanomas. Here we show that the CD34 monoclonal antibody My10 reacts with 19 of 23 (83%) of these lesions, including both those with and without epithelioid features. Five of 10 epithelioid and one of 13 spindled neoplasms lacked detectable muscle-specific actin (MSA), smooth muscle actin (SMA), and desmin; all six were CD34 reactive. Immunoblotting experiments show that the antigen on these stromal neoplasms has a molecular weight identical to that found on hematopoietic cells. The frequency and intensity of the reactivity of GISTs with anti-CD34 antibodies are distinctly higher than those reported for smooth muscle neoplasms of soft tissue and myometrium. This reactivity can be a useful adjunct in the diagnosis of difficult cases, especially in those exhibiting epithelioid morphology.

Actins↗
PubMed1994

Lymphoid neoplasms in patients with rheumatoid arthritis and dermatomyositis: frequency of Epstein-Barr virus and other features associated with immunosuppression.

We recently reported two cases of reversible Epstein-Barr virus (EBV)-associated lymphomas in patients undergoing methotrexate therapy for rheumatic disease. The current study was undertaken to investigate how frequently lymphoid neoplasms in patients with rheumatic disease show features of lymphoproliferations occurring in immunocompromised patients. Eighteen patients (including the two previously reported patients) with rheumatoid arthritis or dermatomyositis who developed lymphoproliferative lesions and on whom detailed clinical information was available were studied. As a group these patients developed a spectrum of lymphoproliferative lesions; however, a subset of patients developed neoplasms with features associated with immunosuppression. The neoplasms occurred in extranodal sites in 10 (56%) patients, showed a diffuse large-cell histology in nine (50%) patients, and contained EBV (EBER1) transcripts and EBV latent membrane protein in six (33%) patients. In three (17%) patients the neoplasms showed the entire constellation of features typical of immunosuppression-associated lymphoproliferations, including extranodal location, large-cell or polymorphous histology, geographic areas of necrosis, and the presence of EBV. These three patients were receiving both steroids and methotrexate at the time they developed their neoplasms. The findings of this study support the hypothesis that a subset of lymphoid neoplasms in rheumatic patients occurs in an immunocompromised setting and suggest that therapeutic immunosuppression may contribute, at least in part, to the development of these lymphoid neoplasms.

Adolescent↗
PubMed1994

A comparative immunohistochemical study of uterine smooth muscle neoplasms with emphasis on the epithelioid variant.

We evaluated the immunophenotypes of 22 spindled and 36 epithelioid uterine smooth muscle neoplasms (SMNs) and 16 extrauterine nongastrointestinal spindled smooth-muscle neoplasms for various markers. The epithelioid neoplasms were subdivided into two histological groups designated true and intermediate, the former showing typical epithelioid features and the latter showing epithelioid features that could be explained by cross-sectioning of blunt spindled cells. Desmin, muscle-specific actin, and smooth muscle actin were equally sensitive in detecting muscle differentiation in all these neoplasms. The true epithelioid variants were more frequently keratin positive but less frequently positive for vimentin, CD34 or the muscle markers, compared with their spindled counterparts. The intermediate epithelioid variants more closely resembled the spindled neoplasms in their immunostaining for muscle markers, vimentin, and CD34 but like the true epithelioid variants were relatively frequently positive for keratin. CD34 was positive in 36% of the spindled and 6% of the true epithelioid uterine SMNs, in most cases faintly. Antikeratin AE1 was positive more frequently than CAM5.2, with 18% of the spindled and 35% of the true epithelioid neoplasms being AE1 positive. The immunophenotype of uterine SMNs, including the epithelioid variant, permits their distinction from carcinomas based on their frequent reactivity for muscle markers in spite of their high rate of keratin positivity. They show sufficient overlap in immunoreactivity with endometrial stromal sarcomas to preclude definitive differentiation from them on immunohistochemical features alone.

Antigens, CD↗
PubMed1994

Expression of CD34 by solitary fibrous tumors of the pleura, mediastinum, and lung.

Solitary fibrous tumors are rare neoplasms that most commonly involve the pleura, mediastinum, and lung. Because they lack distinctive histologic features, immunologic staining has frequently been employed to exclude other neoplasms in the differential diagnosis. Their reported phenotype to date is generally negative, notably for muscle-type actins, desmin, keratin, and S-100 protein. Although this testing is of some help, it does not serve to distinguish all processes in the differential diagnosis, and when it does, it places too great an emphasis on a negative finding to make a diagnosis. We report here that CD34 monoclonal antibodies reacted with 11 of 14 solitary fibrous tumors in paraffin sections. Thus, they provide a positive marker that distinguishes the solitary fibrous tumor from most elements in the differential diagnosis.

Adult↗
PubMed1994

Bcl-2 immunoreactivity in breast carcinoma correlates with hormone receptor positivity.

The protein encoded by the Bcl-2 proto-oncogene has been shown to inhibit programmed cell death and has been primarily studied in hematolymphoid malignancies. Recent work ahs elucidated Bcl-2 expression in nonhematolymphoid malignancies of the lung, prostate, and nasopharynx. Studies of Bcl-2 expression in prostate carcinoma have suggested that its expression may be related to hormonal control. To determine its presence and possible significance in breast carcinoma, a malignancy in which therapy is influenced by hormone receptor status, we used a monoclonal antibody directed against the Bcl-2 gene product to examine Bcl-2 immunoreactivity in a series of paraffin-embedded primary breast tumors. Benign breast tissue showed Bcl-2 positivity in the basal layer and in superficial cells. Twenty-four of 41 (58%) carcinomas were Bcl-2 positive. Staining for Bcl-2 was equivocal in two cases. We identified a strong correlation between Bcl-2 expression and hormone receptor positivity as 23 of 24 (96%) cases that were Bcl-2 positive were estrogen receptor (ER) positive (P = 0.0001) and 21 of 24 (87.5%) were positive for progesterone receptor PR (P = 0.0001). Of 15 Bcl-2-negative cases, 14 (93%) were ER negative and all were PR negative. One case of mucinous carcinoma was ER positive and Bcl-2 negative. Grade 1 and 2 tumors (Scarff-Bloom-Richardson scale) were almost three times as likely to be Bcl-2 positive (90%) as grade 3 tumors (33%) (P = 0.0057). Bcl-2 reactivity appears to be more prevalent in well-differentiated tumors, suggesting that its presence may diminish with loss of differentiation, a hypothesis that is further supported by a subset of cases that were ER negative, Bcl-2 negative, and of poor histological grade. These may be tumors that do not require Bcl-2 inhibition of apoptosis and respond to hormonally independent proliferation factors. Our findings support the hypothesis that Bcl-2 expression may be related to hormonal regulation in breast carcinoma.

Adult↗
PubMed1990

Biosynthesis pathway of gp90MEL-14, the mouse lymph node-specific homing receptor.

The mouse lymph node specific homing receptor gp90MEL-14 is a 95-kDa molecular mass ubiquitinated cell surface molecule involved in the binding of lymphocytes to high endothelial venules in peripheral lymph nodes. The molecule is thought to consist of a core protein to which ubiquitin side chains are covalently bound. Recently we cloned the cDNA encoding the core protein; this cDNA clone encodes for a polypeptide with an estimated molecular mass of 37 kDa. We have studied the biosynthesis of gp90MEL-14 in an effort to explain the difference in molecular mass between the core protein and the 95-kDa mature molecule. Pulse labeling experiments show a rapid synthesis of a 70-kDa precursor form that contains high-mannose N-linked oligosaccharides. On processing of the high-mannose oligosaccharides into complex N-linked oligosaccharides, the precursor matures in a single step into the 95-kDa form. Experiments using deglycosylating enzymes and inhibitors of N-linked glycosylation demonstrate that the molecular mass of deglycosylated gp90MEL-14 is 45 kDa; extensive N-linked glycosylation is responsible for the difference in molecular mass with the mature 95-kDa form. The core protein molecular weight of in vitro transcribed and translated gp90MEL-14 cDNA is consistent with the estimated molecular mass of 37 kDa, calculated from the cDNA sequence of the core protein, and 8 to 10 kDa less than the protein molecular mass of gp90MEL-14 translated in vivo in the presence of tunicamycin (45 kDa). Inasmuch as we have ruled out glycosylation as accounting for this discrepancy, this is consistent with the addition of one ubiquitin moiety to the core protein during biosynthesis. Limited proteolysis confirms the similarity between in vitro transcribed gp90MEL-14 cDNA and the tunicamycin form of gp90MEL-14.

Animals↗
PubMed1990

Autopsy findings after coronary rotational atherectomy.

We describe the findings at autopsy in a patient who underwent Rotablator atherectomy of the right coronary artery. During the procedure, the artery became occluded. Despite attempts to reopen the vessel with balloon angioplasty and emergency coronary artery bypass grafting, the patient developed irreversible cardiac failure and expired 2 days after the Rotablator procedure. At autopsy, the right coronary artery was found to be occluded by thrombus. No evidence of dissection or perforation of the vessel wall was seen. Small intramyocardial arteries and arterioles, downstream from the treated vessel, were embolized by pulverized atheroma.

Angioplasty, Balloon, Coronary↗
PubMed1989

Mouse lymph node homing receptor cDNA clone encodes a glycoprotein revealing tandem interaction domains.

Isolation of a clone encoding the mouse lymph node homing receptor reveals a deduced protein with an unusual protein mosaic architecture, containing a separate carbohydrate-binding (lectin) domain, an epidermal growth factor-like (EGF) domain, and an extracellular precisely duplicated repeat unit, which preserves the motif seen in the homologous repeat structure of complement regulatory proteins and other proteins. The receptor molecule is potentially highly glycosylated, and contains an apparent transmembrane region. Analysis of messenger RNA transcripts reveals a predominantly lymphoid distribution in direct relation to the cell surface expression of the MEL-14 determinant, and the cDNA clone is shown to confer the MEL-14 epitope in heterologous cells. The many novel features, including ubiquitination, embodied in this single receptor molecule form the basis for numerous approaches to the study of cell-cell interactions.

Amino Acid Sequence↗
PubMed1989

Mouse hematopoietic stem-cell antigen Sca-1 is a member of the Ly-6 antigen family.

Recently, hematopoietic stem cells were purified to homogeneity from mouse bone marrow. The protein structure of Sca-1, the cell surface antigen used in the isolation of hematopoietic stem cells, is described here. It is shown that the Sca-1 antigen is a member of the Ly-6 antigen family. The anti-Sca-1 antibody was used in immunohistochemistry experiments to define the structures in several tissues that had previously been shown to contain Ly-6 antigens. In thymus, spleen, and kidney, specific staining of parenchymal cells can be demonstrated, whereas only vasculature reacts with anti-Sca-1 in brain, heart, and liver and possibly in lung.

Animals↗
PubMed1986

Alloantigen recognition is preceded by nonspecific adhesion of cytotoxic T cells and target cells.

T-cell receptors bind antigens only when the antigens are exposed on the cell surface. This can be studied best in the interaction of cytolytic T lymphocytes (CTL) with target cells because the recognition and binding event can be separated from the lytic phase. Studies with CTL clones specific for HLA-A2 and HLA-B7 demonstrated that conjugates of CTL's and target cells can be formed in the absence of specific antigen recognition. Furthermore, T-cell receptor and target antigen cannot interact unless there is conjugate formation. This indicates that nonspecific conjugate formation between CTL's and target cells precedes the recognition of specific antigen by the T-cell receptor.

Antibodies, Monoclonal↗
PubMed1986

Isolation and purification of the human thymocyte antigens T6 and M241.

T6 and M241 antigens are products of the Class I major histocompatibility complex. The T6 and M241 antigens can be detected on human cortical thymocytes and on dendritic cells in the skin by monoclonal antibodies. Here we report a method of purification of the T6 and M241 antigens. Amino acid sequence data of purified antigens indicate that the heavy chains are blocked at their N-termini, whereas the partial N-terminal amino acid sequence of the light chains is identical to that of the human beta 2-microglobulin. In order to obtain sequence data from the heavy chains a method is described for isolation of purified cyanogen bromide fragments by electrophoretic methods.

Amino Acid Sequence↗