MR imaging of a pilomatrixoma.
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Child, Preschool↗
Biomedical subjects
P Möller
Publications and source records attributed to P Möller.
Toxic spongiform leucoencephalopathy after inhaling heroin vapour.
This is a report of clinical, CT and MRI findings in a patient with toxic spongiform leucoencephalopathy after heroin ingestion. The disease is observed in drug addicts who inhale pre-heated heroin. The clinical onset, which usually occurs some days or even longer after the last heroin consumption, is characterized by a cerebellar syndrome. The cerebellar hemispheres, the cerebellar and cerebral peduncles and the pyramidal tract may be affected. Spongiform demyelination is the morphological substrate of the lesions, which are not contrast enhancing, hypodense on CT and hyperintense on T2-weighted MRI. The frequently perfect symmetry of the affection of functional systems points to a toxic and/or metabolic pathophysiological mechanism.
Administration, Inhalation↗
Cutaneous CD30+ lymphoproliferative disorders: expression of bcl-2 and proteins of the tumor necrosis factor receptor superfamily.
The spectrum of CD30+ cutaneous lymphoproliferative disorders is characterized by the histology of a high-grade lymphoma but frequent clinical regression of skin lesions in lymphomatoid papulosis (LyP) and occasional regression in CD30+ large cell lymphomas (LCLs). A recent study shows that apoptosis may be a significant mechanism of regression of LyP (Arch Dermatol 133:828-833, 1997). Therefore, we studied expression of proteins that induce apoptosis, including CD27, CD40, CD95, and nerve growth factor receptor (NGF-R), as well as anti-apoptotic protein bcl-2 in skin lesions from 25 patients within the spectrum of CD30+ cutaneous lymphoma. Our results show consistent expression of CD95 (APO-1/Fas), but rare or absent expression of CD27, CD40, and NGF-R on tumor cells from both regressing LyP lesions and nonregressing CD30+ lymphomas. Bcl-2 was expressed at low levels in LyP and at high levels in pleomorphic CD30+ lymphomas. These results indicate that, in addition to CD30, CD95 expression is preferentially expressed at high levels in all cutaneous CD30+ lymphomas and suggest that CD95 may play a role in the regression of CD30+ skin lesions. Expression of bcl-2 appears to protect tumor cells from apoptosis in CD30+ lymphoproliferative disorders.
Adult↗
CD95(APO-1/Fas)-mediated apoptosis in normal and malignant liver, colon, and hematopoietic cells.
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Apoptosis↗
Dento-maxillofacial sequelae in a child treated for a rhabdomyosarcoma in the head and neck. A case report.
This case report describes severe dento-maxillofacial defects after chemoradiation therapy in a child aged 9 years 6 months with a parameningeal rhabdomyosarcoma. A clinical and radiologic (apical dental radiographs, orthopantograph, lateral skull roentgenogram) dental follow-up over 4 years showed such dental abnormalities as root blunting, mild to severe root shortening, premature closure of the root apices, and severe radiation caries. Craniofacial morphology evaluated by cephalometric analysis and dental models showed deficiency with mandibular and maxillary hypoplasia.
Child↗
Vaccination with IL-7 gene-modified autologous melanoma cells can enhance the anti-melanoma lytic activity in peripheral blood of patients with a good clinical performance status: a clinical phase I study.
Recently, cytokine gene transfer into tumour cells has been shown to mediate tumour regression in animal models via immunomodulation. Consequently, a number of clinical protocols have been developed to treat cancer patients with cytokine gene-modified tumour cells. Here, we report the results of a clinical phase I trial using for the first time autologous, interleukin 7 gene-modified tumour cells for vaccination of ten patients with disseminated malignant melanoma. Melanoma cells were expanded in vitro from surgically removed metastases, transduced by a ballistic gene transfer technique and were then injected after in vitro irradiation s.c. at weekly intervals. Clinically, there was no major toxicity except for mild fever, and no major clinical response towards vaccination was observed. Eight of ten patients completed the initial three s.c. vaccinations and were eligible for immunological evaluation. Post vaccination, peripheral mononuclear cells (PBMCs) were found to contain an increased number of tumour-reactive proliferative as well as cytolytic cells, as determined by a limiting dilution analysis. In three of six patients, the frequencies of anti-melanoma cytolytic precursor cells increased between 2.6- and 28-fold. Two of these patients showed a minor clinical response. Analysis of the autologous tumour cell vaccines regarding IL-7 secretion after gene transfer, HLA class I and class II cell surface expression, secretion of immunosuppressive mediators (TGF-beta1, IL-10) and various melanoma-associated tumour antigens revealed a very diverse expression profile. In conclusion, vaccination using gene-modified autologous melanoma cells induced immunological changes in a group of advanced, terminally ill patients. These changes can be interpreted as an increased anti-tumour immune response. However, immunological modulation was most pronounced in patients in good physical condition. Therefore, patients with minimal tumour load or minimal residual disease might preferentially benefit from tumour cell vaccination in further studies. In order to evaluate the effects of the cytokine gene-modified tumour cell vaccines more precisely, an antigenically better defined vaccine is needed.
Adult↗
Vaccination with IL-12 gene-modified autologous melanoma cells: preclinical results and a first clinical phase I study.
Cytokine gene transfer into tumor cells has been shown to mediate tumor regression and antimetastatic effects in several animal models via immunomodulation. Therefore, clinical protocols have been developed to treat cancer patients with cytokine gene-modified tumor cells. We inserted the genes coding for the p35 and p40 chain of interleukin-12 (IL-12) in two independent eukaryotic expression vectors and transduced melanoma cells of 15 different primary tumor cultures with both plasmids by a ballistic gene transfer approach. Secreted IL-12 demonstrated strong bioactivity by inducing interferon-gamma release from peripheral blood lymphocytes upon coculture with cell culture supernatants after IL-12 gene transfer which could at least partly be blocked by IL-12-specific antisera. Further enrichment of transduced tumor cells by magnetic separation directly after gene transfer increased cytokine secretion from a mean of 119 pg in the unsorted to 507 pg IL-12 (24 h/10(8) cells) in the magnetically enriched cell fraction. Irradiation of these cells led to a further elevation of secreted IL-12 (mean 987 pg). Elevated IL-12 levels were detected over 7 days after irradiation in vitro. In a subsequent first clinical phase I study six patients with metastatic melanoma were vaccinated with autologous, interleukin-12 gene-modified tumor cells. Melanoma cells were expanded in vitro from surgically removed metastases, transduced by ballistic gene transfer, irradiated and were then injected subcutaneously (s.c.) at weekly intervals. Clinically, there was no major toxicity except for mild fever. All patients completed more than four s.c. vaccinations over 6 weeks and were eligible for immunological evaluation. Post-vaccination, peripheral mononuclear cells were found to contain an increased number of tumor-reactive proliferative as well as cytolytic cells as determined by a limiting dilution analysis in two patients. Two patients developed DTH reactivity against autologous melanoma cells and one had a minor clinical response. Biopsies taken from that patient's metastases revealed a heavy infiltration of CD4+ and CD8+ T lymphocytes. In conclusion, vaccination induced immunological changes even in a group of advanced, terminally ill patients. These changes can be interpreted as an increased antitumor immune response.
Adult↗
Abnormal surface expression of sialoglycans on B lymphocyte cell lines from patients with carbohydrate deficient glycoprotein syndrome I A (CDGS I A).
The carbohydrate-deficient glycoprotein syndromes (CDGS) are genetic, multisystemic diseases characterized by deficiencies in the glycosylation of many secretory glycoproteins, lysosomal enzymes, and possibly cell surface glycoproteins resulting in central nervous system abnormalities and frequent early death by infection. Here we examined whether membranous glycoconjugates of lymphocytes are affected by this disorder. For this, we analyzed cell surface-expressed sialoglycans of Epstein Barr virus (EBV)-transformed B cell lines derived from peripheral B lymphocytes of several patients with CDGS I A. These CDG-LCL (lymphoblastoid cell lines) expressed differentiation markers comparable to those of other EBV-transformed B cell lines. No apparent defects in the gross glycosylation process of defined complex glycosylated proteins such as the surface-expressed major histocompatibility complex class I glycoprotein or secreted immunoglobulin (IgM) were identified. However, using a novel flow cytometric enzyme assay to measure cell surface alpha2,6 sialylation on live cells we found that CDG-LCL express less alpha2,6 sialylated glycans in comparison to other EBV-transformed B cell lines. Also, CDG-LCL bound less of the B lymphocyte lectin CD22, specific for alpha2,6 sialylated lactosamines and known to modulate B cell receptor mediated signaling, as demonstrated by using a soluble CD22-immunoglobulin fusion protein in flow cytometry. CDG-LCL showed stronger surface staining with the monoclonal antibody 1B2 which detects a distinct group of surface-expressed lactosaminyl epitopes. After pretreatment with neuraminidase of Newcastle disease virus (NDVN) it became apparent that in CDG-LCL a significantly larger portion of the 1B2 epitopes was sialylated in alpha2,3 linkage as compared to other B cell lines. Intracellular alpha2,6 sialyltransferase activity as well as polymerase chain reaction products specific for four different sialyltransferases did not significantly differ in CDG-LCL as compared to other EBV-B cell lines. Differences in sialylation may be caused by the respective oligosaccharide core structures available for alpha2,6 or alpha2,3 sialylation in CDG-LCL. Therefore, lymphocytes derived from CDGS patients have distinct deviations in their surface-expressed lactosaminoglycan structures which may affect functions as exemplified by reduced interactions of CD22 with its ligands.
B-Lymphocytes↗
Pathogenesis of primary biliary cirrhosis: CD95-induced apoptosis at last?
Apoptosis is a basic mechanism involved both in maintaining tissue homeostasis by elimination of senescent or potentially harmful cells and in the regulation of immune responses. If not properly regulated, however, it may lead to serious tissue damage. CD95(Fas/APO-1) is a surface receptor that mediates apoptosis upon oligomerization by its ligand, CD95L. The CD95/CD95L-system is one of the major effectors of cytotoxicity in inflammation with implications for both the prevention and the pathogenesis of autoimmune diseases. In primary biliary cirrhosis (PBC), an autoimmune disease, apoptosis has been repeatedly suspected to be the mechanism leading to progressive destruction of bile ducts. The role of apoptosis and its possible molecular inducers in PBC are discussed.
Apoptosis↗
[Analysis of chromosome copy number changes in leiomyosarcoma through molecular cytogenetic methods].
Leiomyosarcoma (LMS) is a rare type of malignant soft tissue tumor occurring predominantly in adults. Up to now only few zytogenetic data resulting from chromosomal banding analyses were obtained from this tumor type. In general, highly complex karyotypes were observed, but no recurrent chromosomal aberrations could be identified. The aim of the present study was to analyze chromosomal imbalances in 14 cases of LMS using comparative genomic hybridization (CGH). Imbalances were detected in all cases analyzed, with chromosomal gains occurring more frequently than losses (9.9 gains/case vs. 6.9 losses/case, respectively). Chromosome arms predominantly overrepresented included Xp (9/14 cases), 5p and 8q (8/14 each), as well as 17p and 17q (6/14 each). Nineteen distinct high level amplifications, indicative for the location of relevant proto-oncogenes in LMS, were identified in nine different tumors. Interestingly, in three cases chromosomal arm 17p was involved. Interphase analysis with probes derived from the commonly amplified region 17p11-p12 revealed, that the tre oncogene is co-amplified and therefore could play a relevant role in LMS development. With regard to losses chromosome 13q was affected in 12/14, 10q in 8/14, and 2p as well as 2q in 7/14 tumors, respectively. The frequent deletions of chromosome 13 with a minimal affected region 13q14-q15 strongly support preliminary molecular evidence, that loss of the RB1 tumor suppressor gene is a critical step in LMS tumorigenesis.
Adult↗
A pancolitis resembling human ulcerative colitis (UC) is induced by CD4+ TCR alphabeta T cells of athymic origin in histocompatible severe combined immunodeficient (SCID) mice.
CD4+ TCRalphabeta+ T cells from the colonic lamina propria of athymic (nude) mice were adoptively transferred into histocompatible (SCID) mice homozygous for the autosomal recessive mutation scid (severe combined immunodeficiency). Transfer of these extrathymic CD4+ T cells into SCID mice induced a pancolitis in the adoptive host. The histopathology of this inflammatory response was restricted to the colon and closely resembled human UC. CD4+ T cells infiltrating the colonic lamina propria of diseased SCID mice displayed the surface phenotype of mucosa-seeking memory/effector cells, expressed interferon-gamma (IFN-gamma), and lysed targets in a Fas (CD95)/FasL-dependent pathway. Massive accumulation of oligoclonal CD4+ T cells of athymic origin with the phenotype of Th1 memory/effector T cells in the colonic lamina propria of a histocompatible, immunodeficient host elicits a pancolitis that morphologically mimics human UC.
Adoptive Transfer↗
Multiple endocrine neoplasia type 2-associated RET proto-oncogene mutations do not contribute to the pathogenesis of sporadic parathyroid tumors.
BACKGROUND: Parathyroid disease occurs sporadically or as part of hereditary multiple endocrine neoplasia (MEN) syndrome. The aim of this study was to evaluate the possible role of the RET proto-oncogene not only in hereditary MEN 2-associated hyperparathyroidism but also in different forms of sporadic hyperparathyroidism. METHODS: We investigated 22 patients with parathyroid disease whose family history and results of laboratory and clinical examinations excluded MEN 2 syndrome. DNA extractions of histologically confirmed tumor tissue of patients with primary hyperparathyroidism (n = 18), renal hyperparathyroidism (n = 2), and parathyroid carcinoma (n = 2) were performed. Using solid phase DNA sequencing, mutation analysis of polymerase chain reaction amplified products focused on exons 10, 11, and 16 of the RET proto-oncogene. Parathyroid tissue from four patients with known MEN 2A served as positive controls. RESULTS: No mutations of the codons 609, 611, 618, 620, 634, and 918 were found in the sporadic parathyroid tumors analyzed. DNA sequencing revealed heterozygous mutations in codon 634 of the RET proto-oncogene in four parathyroid glands from four patients with MEN 2A. CONCLUSIONS: Mutations of the RET proto-oncogene contributing to MEN 2 syndromes are absent in sporadic parathyroid tumors. Our data in conjunction with the literature suggest at least three different modes of tumorigenesis in parathyroid disease.
Adenoma↗
Pleural mesothelioma mimics the integrin profile of activated, sessile rather than detached mesothelial cells.
Mesothelial cells (MC) form a polarized monolayer lining serosal cavities. During serositis, the MC lining undergoes hyperplasia, and MC are shed into effusions. During these processes, contact with basement membrane and, ultimately, neighboring cells is at least temporarily lost, suggesting regulated alterations in cell/matrix and cell/cell adhesion. Such interactions are primarily mediated by integrins. Malignant mesothelioma has a growth pattern characterized by lateral, limited invasive but contiguous spread. During serositis, activated MC, both sessile and detached, expressed an extended spectrum of beta1, beta3 and beta4 integrins compared with resting MC, as shown by immunohistology. Malignant mesothelioma had an integrin repertoire and a subcellular distribution resembling that of activated sessile rather than floating MC. In vitro, MC exposed a more comprehensive pattern of integrins than that of the newly established mesothelioma cell lines ME-HD-1 and ME-HD-2, as shown by flow cytometry. MC consistently adhered better than mesothelioma cells to laminin, tenascin, fibronectin and collagen type IV. Adhesion of MC and mesothelioma cells to these matrix proteins was, at least in part, mediated via beta1 integrins. The different integrin profiles and adhesion properties of cultured MC and mesothelioma cells may reflect a limited functional differentiation of the latter.
Antibodies, Monoclonal↗
[Private practitioners see through Ringholm's demagogy].
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Private Practice↗
[How does Bosse Ringholm calculate? The county council saves billions with the new tariffs].
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Cost Savings↗
Somatic gene therapy and its implications in melanoma treatment.
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Clinical Trials as Topic↗
CD95 (APO-1/Fas)-mediated apoptosis in colon epithelial cells: a possible role in ulcerative colitis.
BACKGROUND & AIMS: Ligation of CD95 (APO-1/Fas) by antibody or CD95 ligand (CD95L) induces apoptosis and, in some cell lines, growth. Normal colonic epithelial cells constitutively express CD95. The function of CD95 on colonocytes is unknown. The aim of this study was to elucidate the role of epithelial CD95 in the normal colon and in ulcerative colitis. METHODS: Intact colonic crypts were isolated, and the effects of CD95 ligation in vitro were studied. CD95L-expressing cells and apoptotic cells were detected in situ by RNA hybridization, immunohistochemistry, and DNA nick end labeling. RESULTS: On CD95 ligation, isolated colonic crypt cells underwent apoptosis within 4 hours. No growth-promoting effect was observed. In normal colon, CD95L expression was restricted to few mononuclear cells randomly scattered within the lamina propria. Therefore, the CD95-CD95L system is very unlikely to operate in the regeneration of the colonic epithelium. However, in ulcerative colitis, the number of interstitial CD95L+ cells and the frequency of apoptosis in both lamina propria and epithelium were increased considerably. Further, a focal association of subepithelial CD95L+ mononuclear cells and epithelial apoptosis was observed. CONCLUSIONS: In ulcerative colitis, soluble CD95L-mediated epithelial apoptosis may lead to a breakdown of the epithelial barrier function facilitating the invasion of pathogenic microorganisms.
Apoptosis↗
Qualitative and semi-quantitative value of a modified 13C-urea breath test for identification of Helicobacter pylori infection.
OBJECTIVE: The 13C-urea breath test (13C-UBT) is the method of choice in evaluating the success of therapy for eradication of Helicobacter pylori infection. For reasons of cost efficiency and practicability, urea dose and measurement duration have been reduced and the DOB (delta over baseline) cutoff level with the highest predictive value determined. Further, the efficacy of the modified 13C-UBT as a semi-quantitative test method was evaluated by comparison with histologically determined bacterial infiltration. METHODS: In a prospective study, a modified 13C-UBT with reduced urea dose (75 mg) and shortened measurement duration (30 min) was administered to 145 patients. The DOB cutoff with the highest predictive value was determined using relative operating characteristic analysis. Reference methods included histology, bacterial culture and the rapid urease test. The DOB value was compared with the histologically determined grade of bacterial infiltration and the correlation evaluated using the Spearman ranking method. RESULTS: Reduction of the DOB cutoff level from 5.0 per thousand to 3.5 per thousand led to significant improvement in sensitivity (78.9% vs. 91.2%) and accuracy (88.6% vs. 90.2%) of the 13C-UBT. Only five of 57 infected patients were incorrectly reported as non-infected after modification of the DOB level. In two of three patients in whom histological findings were negative but the 13C-urease test positive, bacterial growth was observed at culture. The DOB level correlated significantly with histological grade of bacterial infection. CONCLUSION: The modified 13C-UBT proved to be a sensitive, practicable and cost-effective method for detecting H. pylori infection and permits a semi-quantitative estimation of bacterial infiltration.
Adolescent↗