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P Möller

Publications and source records attributed to P Möller.

At least 109 records · Page 6Linked to original sources
PubMed1997

Serum levels of carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen and laminin P1 in Duchenne muscular dystrophy.

The striking proliferation of connective tissue in Duchenne muscular dystrophy is attributed, besides other components of the extracellular matrix, to an increase of endomysial and perimysial type III and type I collagen. We investigated if muscle fibrosis correlates to an increased serum concentration of procollagen I or III. Therefore, we measured the serum levels of carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen and laminin P1 in 20 boys with progressive muscular dystrophy (16 definite Duchenne muscular dystrophy, 2 suspected of Duchenne muscular dystrophy, 2 Becker muscular dystrophy). In contrast to collagen I and III the expression of laminin in the basement membrane is known to be normal in Duchenne muscular dystrophy. There was no significant alteration of serum concentration of procollagen III N-peptide, procollagen I C-peptide and laminin P1 in boys with Duchenne muscular dystrophy. Measuring these parameters is not useful for investigating the extent of muscle fibrosis or for monitoring the effect of therapeutic trials such as steroid treatment.

Adolescent↗
PubMed1997

Treatment outcome and prognostic factors for primary mediastinal (thymic) B-cell lymphoma: a multicenter study of 106 patients.

PURPOSE: To define clinicopathologic features, response to treatment, and prognostic factors of primary mediastinal B-cell lymphoma (MBL), a CD20+ tumor recognized as a distinct entity among non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: One hundred six patients presented with disease confined to thorax (86%), bulky mediastinum (73%), superior vena cava syndrome (47%), and contiguous infiltration (57%). Ninety-nine received doxorubicin-containing chemotherapy (CHT). RESULTS: Thirty-five of 99 patients were primarily CHT-resistant, and 64 responded: 23 achieved complete response (CR) and 41 achieved response with residual mediastinal abnormality. Seventy-seven percent of responders received mediastinal radiotherapy (RT). Of 64 responders, 18 (28%) relapsed: none of 23 CR patients and 18 of 41 (44%) with residual mediastinal abnormality. Relapse-free survival rate of responders was 71% at 3 years. Actuarial 3-year survival rate was 52% for all patients and 82% for responders. Predictive factors of poor outcome were identified by logistic regression; Cox survival analysis was performed on death and relapse. Pericardial effusion (P < .001) and Eastern Cooperative Oncology Group (ECOG) performance status > or = 2 (P = .009) predicted nonresponse (NR) and affected survival. Less than partial midway response to CHT predicted NR to subsequent therapies. Bulky disease was related to persistent mediastinal abnormality and risk of relapse (P = .025). CONCLUSION: MBL is an aggressive NHL with unique clinicopathologic aspects, often refractory to current CHT designed for high-grade NHL. Poor performance status and pericardial effusion predict NR and poor survival. Inadequate response after the first courses of front-line CHT predicts failure of subsequent treatment. Responders with bulky mediastinum or residual mediastinal abnormality after CHT are at risk of relapse. These factors should help to select high-risk patients for intensive treatments.

Adolescent↗
PubMed1997

Primary mediastinal B-cell lymphoma: update of its clinicopathologic features.

The peculiar clinical, histomorphological and biological characteristics of PMBCL are reviewed. Special emphasis is given to the frequent aggressive clinical behaviour of this lymphoma in which conventional prognostic factors seem inadequate to identify high risk cases. The need for new clinical and/or biological prognostic markers is stressed.

Biomarkers, Tumor↗
PubMed1997

NPM/ALK fusion mRNA expression in Hodgkin and Reed-Sternberg cells is rare but does occur: results from single-cell cDNA analysis.

BACKGROUND: The translocation t(2;5)(p23;q35) leads to the fusion of the nucleophosmin gene (NPM) on chromosome 5q35 to the recently described receptor kinase ALK on 2p23. It is characteristic of a subgroup of CD30+ large-cell anaplastic non-Hodgkin's lymphoma (ALCL). Since some cases of Hodgkin's disease (HD) and ALCL share common features, a common pathogenesis has been proposed in a report of the expression of NPM/ALK fusion mRNA in 11/13 Hodgkin's lymphomas. PATIENTS AND METHODS: We approached this question by micro-manipulatory isolation of single Hodgkin and Reed-Sternberg (H-RS) cells and subsequent RT-PCR amplification of NPM/ALK fusion cDNA from these single cells. RESULTS: Specificity of cell selection was shown by the HD-specific pattern of EBV-gene expression in single H-RS cells. In 4 out of 7 cases, NPM/ALK fusion cDNA was detected in the RNA from whole lymph node tissue. In 2 out of 9 cases, NPM/ALK fusion sequences were amplified from single H-RS cells, albeit in a very low frequency (< 5%). CONCLUSIONS: These data indicate that NPM/ALK fusion transcripts do not play an early role in the pathogenesis of HD. Whether the rare expression of NPM/ALK is the result of clonal heterogeneity or an indication for clonal evolution and progression toward ALCL can only be answered by the repeated analysis of indicator cases during the course of the disease.

Adolescent↗
PubMed1997

High-level DNA amplifications are common genetic aberrations in B-cell neoplasms.

Gene amplification is one of the molecular mechanisms resulting in the up-regulation of gene expression. In non-Hodgkin's lymphomas, such gene amplifications have been identified rarely. Using comparative genomic hybridization, a technique that has proven to be very sensitive for the detection of high-level DNA amplifications, we analyzed 108 cases of B-cell neoplasms (42 chronic B-cell leukemias, 5 mantle cell lymphomas, and 61 aggressive B-cell lymphomas). Twenty-four high-level amplifications were identified in 13% of the patients and mapped to 15 different genomic regions. Regions most frequently amplified were bands Xq26-28, 2p23-24, and 2p14-16 as well as 18q21 (three times each). Amplification of several proto-oncogenes and a cell cycle control gene (N-MYC (two cases), BCL2, CCND2, and GLI) located within the amplified regions was demonstrated by Southern blot analysis or fluorescence in situ hybridization to interphase nuclei of tumor cells. These data demonstrate that gene amplifications in B-cell neoplasms are much more frequent than previously assumed. The identification of highly amplified DNA regions and genes included in the amplicons provides important information for further analyses of genetic events involved in lymphomagenesis.

Cell Cycle Proteins↗
PubMed1997

Transient absence of CD44 expression and delay in development by anti-CD44 treatment during ontogeny: a surrogate of an inducible knockout?

Because the lack of some adhesion molecules induced by site-directed mutagenesis has been described to be lethal, whereas the lack of others apparently has no effect, we were interested in seeing whether the developing organism might gradually adapt to the absence of adhesion molecules. Therefore, we chose a form of transient interference by i.v. injection of antibody into pregnant rats. As a model, we selected CD44, which has been reported to play a key role during embryogenesis. Rats received either an antibody recognizing an epitope on the CD44 standard isoform (CD44s) or on exon v6 (CD44v6). In the presence of anti-CD44s, delivery was frequently delayed, and intrauterine abortions were often observed. The fetuses were smaller, particularly the anlage of the hair follicle of the whisker, and the formation of alveoli in the lung, of the tubular system of the kidney, and of villi in the gut was delayed. The development of fetuses receiving anti-CD44v6 was hampered until days 16-18 of gestation. Immunodetection revealed a weaker expression of the target molecules at the implantation site and the complete absence of CD44s and CD44v6 expression in fetal tissue until day 12. During the late stages of gestation, the expression pattern of CD44 resembled that of 2-3-day-younger fetuses of untreated rats. Interestingly, degradation of hyaluronate was also delayed, particularly in the kidney. Thus, the diaplacental antibody passage was very efficient and should make it possible to obtain a clearly defined and differentiated concept of the requirements for the CD44 molecule during ontogeny and also for fail-safe mechanisms. Both experiences may be missed in the knockout proper.

Animals↗
PubMed1996

High incidence of chromosomal imbalances and gene amplifications in the classical follicular variant of follicle center lymphoma.

The classical follicular variant of follicle center lymphoma (FCL-fo) is associated with the chromosomal translocation t(14;18)(q32;q21). However, the sole presence of this translocation is not sufficient for malignant transformation, as demonstrated by experiments in a transgenic mouse model. Most of the secondary changes, which play a central role in tumor development and progression and which are presumed to be of prognostic value, are gains and losses of chromosomal material. We analyzed 28 FCL-fo patients using comparative genomic hybridization (CGH). The most frequent imbalances were gains on chromosomes X, 7, 8, 12, and 18 as well as losses of material on chromosome arm 6q. For chromosomes X, 8, 12, and 18, the CGH data allowed further narrowing of the relevant subregions. In addition, novel high-level DNA amplifications were identified in five instances mapping to chromosome bands 1p36, 6p21, 8q24 (2 patients), and 12q13-14. Previously, such amplifications have been identified very rarely in lymphomas. In the 2 patients with amplifications mapping to chromosomal band 8q24, involvement of the MYC proto-oncogene in the amplification unit was demonstrated by Southern blot analysis. These data provide further entry points for studies to identify genes relevant for tumor progression in FCL-fo.

Adult↗
PubMed1996

[Histaminosis].

Explore the source record for details and available documents.

Angioedema↗
PubMed1996

Primary mediastinal (thymic) B-cell lymphoma is characterized by gains of chromosomal material including 9p and amplification of the REL gene.

Primary mediastinal (thymic) B-cell lymphoma is a high-grade non-Hodgkin's lymphoma with unique features. By using comparative genomic hybridization and interphase cytogenetics, 26 tumors were analyzed to identify genomic imbalances. Gains of chromosomal material were much more frequent than losses (110 v 10) and involved chromosomes 9p, 12q, and Xq (31% to 50%). Interestingly, gain of Xq coincided with gain of 9p. Distinct high-level amplifications were found in four subregions. In 2 cases, amplifications of proto-oncogene REL were shown by filter hybridization, indicating a possible pathogenic role of this gene. The characteristic pattern of chromosomal imbalances distinct from other B-cell lymphomas suggests a specific pathway of genetic changes associated with this lymphoma.

Aneuploidy↗
PubMed1996

Differential regulation of human T cell responsiveness by mucosal versus blood monocytes.

Human intestinal T lymphocytes are constantly exposed to a large number of foreign antigens without developing a systemic immune response. One crucial mechanisms leading to this intestinal hyporesponsiveness is based on impaired signal transduction through the T cell receptor/CD3 complex in lamina propria T lymphocytes (LP-T). In this study, we addressed the question whether a lack of co-stimulatory/progression signals might also contribute to LP-T hyporesponsiveness. To this end, isolated human monocyte populations from the intestinal lamina propria were obtained and their phenotypes as well as their capacity to promote T cell activation studied. Here, we demonstrate that lamina propria macrophages (LP-MO), in contrast to peripheral blood monocytes (PB-MO), do not support proliferation of either LP-T or PB-T. This may be due to the low expression of ligands (CD54, CD58, CD80) for the T cell accessory receptors CD11/18, CD2 and CD28/CTLA-4 on mucosal macrophages. Thus, down-regulation of both recognition/competence and co-stimulatory/progression signals contribute to intestinal hypo- or unresponsiveness.

Antigens↗
PubMed1996

L1 adhesion molecule on human lymphocytes and monocytes: expression and involvement in binding to alpha v beta 3 integrin.

The L1 adhesion molecule is a member of the immunoglobulin (Ig) superfamily initially identified in the nervous system which contains six Ig-like domains. Besides the known L1-L1 homotypic interaction, L1 was recently shown to bind to very late antigen (VLA)-5 in the mouse and alpha v beta 3 in the human. The sixth Ig domain is critical for this function. We now demonstrate that human CD4+ peripheral blood T lymphocytes, monocytes and B lymphocytes, but not CD8+ T lymphocytes, express L1. When compared to the expression of CD31, another ligand for alpha v beta 3 on T lymphocytes, only a small proportion of cells were CD31+L1+ double positive. L1 was also detected on the surface of human monocytic and lymphoid tumor lines and was shown to have a molecular mass of approximately 220 kDa, similar to the molecule present on neuroblastoma cells. The function of the sixth Ig domain of human L1 as an integrin ligand was also investigated. Using an RGD-containing peptide derived from the sixth Ig domain as well as a fusion protein of the sixth Ig domain of L1 and the Fc portion of human IgG1 (6.L1-Fc), we demonstrated the binding of human MED-B1 (alpha v beta 3hi, alpha 5 beta 1lo) tumor cells and this binding was blocked by alpha v-specific mAb. In contrast, human Nalm-6 cells (alpha v beta 3lo, alpha 5 beta 1hi) did not bind to the 6.L1-Fc fusion protein. MED-B1 cells could also be stained with the 6.L1-Fc fusion protein. Our results suggest that human L1 binds predominantly to alpha v beta 3 and that its presence on leukocytes could be important for adhesion and migration.

Amino Acid Sequence↗
PubMed1996

Expression of CD44 splice variants in human skin and epidermal tumours.

Splice variants of the adhesion molecule CD44 (CD44v) are important in the lymphatic spread of rat carcinoma cells. In several human tumours expression of CD44v correlates with tumour progression. However, little is known about the physiological functions of distinct variant exons. Here we report on the immunohistological evaluation of CD44 expression in normal human skin and epidermal tumours which do not metastasise, or do so vary rarely. Frozen tissues were stained with a panel of monoclonal antibodies, recognizing epitopes of the CD44 standard isoform, as well as of variant exons v5, v6, v7, v7-v8 and v10. Stratum basale and spinosum as well as the root shaft of hairs reacted strongly with the whole panel of anti-CD44 antibodies. Stratum corneum, acinar cells of sebaceous and eccrine sweat glands stained with anti-CD44v5, anti-CD44v6 and anti-CD44v7, but not with anti-CD44v10, the latter recognizing the "epithelial isoform" (CD44v8-v10) of CD44. Ductal cells of glands and apocrine glands did not express CD44v. Compared with its expression in normal human skin, CD44v expression was reduced in basal cell carcinoma and squamous cell carcinoma of the skin. This was particularly true of CD44v10. The expression of CD44v in normal skin and dermal appendages indicates that not all combinations of variant exons are involved in tumour progression. Since the epithelial isoform is particularly downregulated in basal cell carcinoma and squamous cell carcinoma of the skin, it is unlikely that exons v8-v10 play a role in tumour progression. Rather, they may be of functional importance in maintenance of the epidermal structure.

Animals↗
PubMed1996

Transient expression of CD44 variant isoforms in the ontogeny of the rat: ectoderm-, endoderm- and mesoderm-derived cells express different exon combinations.

Expression on rat tumor cells of CD44 variant isoforms containing exons v4-v7 or v6-v7 has been described as sufficient for initiation of the metastatic cascade. The question arose as to whether physiological programs may be reactivated by particular CD44 isoforms. With this in mind, expression of mRNAs for the CD44 isoforms was surveyed during ontogeny of the rat. Using available monoclonal antibodies, expression of the CD44 standard isoform (CD44s) and of an epitope of CD44 exon v6 (CD44v6) were evaluated by immunohistology also. While CD44s was expressed in cells of all three germ layers, CD44v6 expression was restricted to distinct epithelial layers and cells of the hematopoietic system. During ontogeny, expression of CD44v6 was first noted in the neural tube and the leading epithelial layer of the limb buds. Later, anti-CD44v6 (1.1ASML) stained basal layers of the epidermis, the epithelium of the gut, and the acini of the submandibular gland. Strong, but transient expression of CD44v6 was seen during lung development, in hematopoietic stem cells of the liver, in thymic epithelia and early thymic immigrants. Expression in these organs was downregulated shortly before or after birth. As revealed by Southern blotting after use of the reverse transcriptase polymerase chain reaction (RT-PCR), most CD44v6-positive organs contained more than one CD44 variant isoform, and the expression patterns differed between individual organs. Hematopoietic cells preferentially expressed exons v4-v7, endodermal tissue exons v4-v10 and only in the epidermis were exons v1-v10 detected. The temporally regulated expression during ontogeny and the different exon compositions suggest a pivotal role of CD44 isoforms particularly in hematopoesis and in pattern formation by instructive epithelia.

Animals↗
PubMed1996

Rapid onset of apoptosis in vitro follows disruption of beta 1-integrin/matrix interactions in human colonic crypt cells.

BACKGROUND & AIMS: Apoptosis by loss of adherence is a recently described phenomenon termed "anoikis." beta 1, integrins are heterodimeric surface molecules mediating adhesion to the extracellular matrix. The aim of this study was to address whether anoikis accounts for the elimination of senescent enterocytes and, if so, whether beta 1 integrins are involved. METHODS: Whole crypts were isolated from normal human colonic mucosa and examined in vitro. RESULTS: The vast majority of cells in resuspended crypts rapidly underwent apoptosis within 4 hours. Apoptosis was partially inhibited when cells had contact with collagen I-coated membranes or when whole crypts were embedded in a collagen gel. Preincubation of crypts with an inhibiting anti-beta 1 antibody before readhesion caused a much higher apoptotic rate. Confocal microscopy of embedded crypts revealed two critical zones of high sensitivity to temporary loss of adherence: the base of the crypts where stem cells are supposed to reside and the crypt mouth including the surface epithelium. CONCLUSIONS: Survival of colonic epithelia crucially depends on matrix adhesion and is likely to be guaranteed by beta 1-integrin/ matrix interaction. The data strongly suggest that anoikis is the way senescent colon cells die.

Apoptosis↗
PubMed1996

Early detachment of colon carcinoma cells during CD95(APO-1/Fas)-mediated apoptosis. I. De-adhesion from hyaluronate by shedding of CD44.

Ligation of CD95 (APO-1/Fas) cell surface receptors induces death in apoptosis-sensitive cells. Induction of apoptosis in adherent gamma interferon-stimulated HT-29 and COLO 205 colon carcinoma cells by cross-linking CD95 with anti-APO-1 monoclonal antibody resulted in detachment of the cells from hyaluronate starting about 1 h after antibody exposure. Loss of adhesion was paralleled by a substantial reduction of the multifunctional cell surface adhesion molecule CD44. As evidenced by cycloheximide treatment, this effect was not caused by impaired protein synthesis. Depletion of surface CD44 was also not due to membrane blebbing, since cytochalasin B failed to inhibit ascension from hyaluronate. Instead, ELISA and time kinetics showed increasing amounts of soluble CD44 in the supernatant of CD95-triggered cells. SDS-PAGE revealed that soluble CD44 had an apparent molecular mass of about 20 kD less than CD44 immunoprecipitated from intact cells. Thus, CD95-triggering induced shedding of CD44. Shedding is a novel mechanism operative in early steps of CD95-mediated apoptosis. Shedding surface molecules like CD44 might contribute to the active disintegration of dying epithelial cells in vivo.

Apoptosis↗
PubMed1996

Interleukin-7. Biology and implications for dermatology.

In recent years, it has become apparent that IL-7, originally characterized as a growth factor for pre-B lymphocytes, also has important implications for the skin. Keratinocytes have been shown to produce IL-7. which in turn can elicit a variety of biological responses on several cell types residing in the skin. IL-7 has been demonstrated to augment the cytolytic activity of cytotoxic T cells (CTL) and natural killer (NK) cells against various neoplastic targets including melanoma cells. Proliferation and long-term survival of murine dendritic epidermal T lymphocytes (DETC) in vitro is supported by IL-7. IL-7 also induces secretion of inflammatory cytokines by monocytes/macrophages and renders these cells to become tumoricidal against melanoma cells. Normal and malignant melanocytes respond to IL-7 with increased expression of intercellular adhesion molecule (ICAM-1). In addition, IL-7 has been shown to act as growth factor for Sezary cells, suggesting a role of keratinocyte-derived IL-7 in the pathogenesis of cutaneous T cell lymphoma. Because of the potent in vitro immunomodulatory effects of IL-7 which have been confirmed in mouse tumor models, IL-7 may become a valuable additional agent to immunotherapeutical regimens currently studied in patients with advanced melanoma. This review summarizes our present knowledge about the molecular and immunological properties of IL7 with emphasis on the effects of that cytokine within the cutaneous compartment and the potential clinical utility in dermatology.

Animals↗