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J G Müller

Publications and source records attributed to J G Müller.

At least 37 records · Page 2Linked to original sources
PubMed1998

The cytomorphological spectrum of mantle cell lymphoma is reflected by distinct biological features.

Mantle cell (centrocytic) non-Hodgkin's lymphoma (MCL) is a malignant tumour with unique biological features. The pathogenesis of MCL seems to be strongly associated with aberrant function of the cell cycle. 110 cases of MCL have been analysed for their cytomorphological features, mitotic and proliferation indices, bcl-1 rearrangements, p53 expression patterns and DNA content by both interphase cytogenetic as well as DNA flow cytometric analyses. According to cytomorphology, three subtypes were recognized: a common, a lymphoblastoid and a pleomorphic variant of MCL. Blastic MCL subtypes were characterized by distinctly elevated mitotic and proliferation indices, frequent bcl-1 rearrangements at the MTC locus, and overexpression of p53. The most interesting finding, however, was a striking tendency of blastoid MCL subtypes to harbour chromosome numbers in the tetraploid range, a feature clearly separating these neoplasms from other types of B-cell NHL and possibly being related to its unphysiological expression of cyclin D1. Although characterised by a uniform immunophenotype and common biological background, MCL shows a broad spectrum of morphological features ranging from small cell to blastic types, and this spectrum is mirrored by distinct biological features.

Cell Division↗
PubMed1998

Objective nuclear grading for node-negative breast cancer patients: comparison of quasi-3D and 2D image-analysis based on light microscopic images.

In a retrospective investigation for a new image-analytical nuclear grading method, we used 145 routine hematoxylin and eosin-stained, paraffin-embedded tissue sections from node-negative breast carcinomas. Cell fields of primary tumors were scanned in a light microscope in successive focus levels in 1-micron steps for thick sections (> or = 5 microns: quasi-3D analysis) and in one focus position for thin sections (< 5 microns: 2D analysis). After image-segmentation, nuclear features for texture and chromatin distribution were calculated. A binary classification tree was constructed for determination of two mathematically defined classes of high- and low-risk tumor cell nuclei. After fixing a cut-point for the portion of high-risk tumor cell nuclei per patient, it was possible to distinguish two different groups with significantly different relapse rates of 4.2% and 74.5% in quasi-3D analysis and 0.0% and 52.0% in 2D analysis, respectively. Large differences between quasi-3D and 2D analysis were only present in the classification of nonrelapse patients, whereas nearly all patients with relapse had more than 50% high-risk tumor cell nuclei. The results show that the information in thicker tissue sections contains important additive components in the third dimension, with respect to the detection of chromatin structure and distribution. This advantage should be exploited for the development of an objective image-analytical nuclear grading system as a highly significant prognostic marker.

Adult↗
PubMed1998

[The stepchild of intestinal diagnosis. Evaluation of radiologic methods in the diagnosis of leiomyoma of the small intestine].

PURPOSE: Various radiological methods to diagnose small bowel neoplasms and problems of differential diagnosis specially considering leiomyomas are discussed. PATIENTS AND METHODS: Two patients with leiomyoma of the ileum underwent enteroclysis, computed tomography of the abdomen, intra-arterial DSA and colour Doppler sonography. Another patient with leiomyosarcoma just underwent CT of the abdomen with CT-guided biopsy. RESULTS: Due to the homogenous density and the smooth surface of the tumors in computed tomography and respectively enteroclysis and the presentation of the tumor vascularisation in the angiography and Colour Doppler sonography in both patients a leiomyoma of the small bowel was diagnosed. Postoperatively this diagnosis was histologically confirmed. The CT-findings of the patient with leiomyosarcoma were not suspicious of a malignant tumor. CONCLUSION: Radiologically it is not possible to determine the dignity of smooth muscle cell tumors safely. That is the reason why the diagnosis has to be achieved operatively. But the histopathological diagnosis based on the mitotic rate may be difficult. Therefore the after care has to be carried out thoroughly.

Aged↗
PubMed1997

Sequence-specific antiproliferative effects of antisense and end-capping-modified antisense oligodeoxynucleotides targeted against the 5'-terminus of basic-fibroblast-growth-factor mRNA in coronary smooth muscle cells.

Basic fibroblast growth factor (bFGF), a potent mitogen for arterial smooth muscle cells, has been shown to play a fundamental role in the pathogenesis of arteriosclerosis and restenosis by stimulating the proliferation of vascular smooth muscle cells. We found that partially phosphorothioate-modified 15-residue antisense oligodeoxynucleotides complementary to bFGF mRNA at 0.1-2.0 microM block growth and division of cultured human and bovine coronary smooth muscle cells in a dose-dependent manner. The effect is sequence specific at low (0.1-0.5 microM) nontoxic concentrations. It is associated with inhibition of expression of pericellular and intracellular bFGF, with a decreased de novo synthesis of bFGF and is partly reversible by the addition of exogenous (recombinant) bFGF. The antisense effect lasts 48-72 h and diminishes thereafter. If the antisense oligodeoxynucleotide medium is replaced by an oligonucleotide-free medium after 24 h, the [3H]thymidine incorporation rate returns to control levels. Under the same conditions, the corresponding sense oligodeoxynucleotide exerts negligible nonspecific inhibitory actions. The antiproliferative potency of the 15-residue antisense oligodeoxynucleotide is markedly enhanced by adding 3-4 nonbase-pairing guanosine residues at the 5'- and 3'-termini of the 15-residue antisense oligonucleotide. The data implicate bFGF in the process of smooth muscle cell proliferation and an effective and specific antiproliferative potency of bFGF-specific antisense oligonucleotides. The results point to possible new therapeutic strategies for the use of antisense methodology in the suppression of post-angioplasty restenosis.

Animals↗
PubMed1997

Blastoid variants of mantle cell lymphoma: frequent bcl-1 rearrangements at the major translocation cluster region and tetraploid chromosome clones.

Sixty-four cases of mantle cell (centrocytic) non-Hodgkin's lymphomas have been analyzed for their cytomorphologic features, proliferation indices, bcl-1 rearrangements, p53 expression patterns, and DNA content by both interphase cytogenetic and DNA flow cytometric analyses. According to cytomorphology, three subtypes were recognized: a common, a lymphoblastoid, and a pleomorphic variant of mantle cell lymphoma (MCL). Blastoid MCL subtypes were characterized by distinctly elevated mitotic counts (57 and 51/10 HPF v 21/10 high-power fields in common MCL), proliferation indices (58% and 53% v 27% in common types, respectively; P < .001), frequent bcl-1 rearrangements at the major translocation cluster locus (59% v 40%), and overexpression of p53 (21% v 6%). However, the most interesting finding was a striking tendency of blastoid MCL subtypes to harbor chromosome numbers in the tetraploid range (36% of lymphoblastoid and 80% of pleomorphic types v 8% of common variants, P < .001), a feature clearly separating these neoplasms from other types of B-cell non-Hodgkin's lymphoma and possibly being related to cyclin D1 overexpression. Our data indicate that, although characterized by a uniform immunophenotype and common biologic background, MCL shows a broad spectrum of morphologic features ranging from small cell to blastoid types and that the morphologic spectrum is mirrored by distinct biologic features.

Cell Division↗
PubMed1997

Histological changes in the colonic mucosa following irrigation with short-chain fatty acids.

OBJECTIVES: Short-chain fatty acids (SCFAs) derived from bacterial fermentation of complex carbohydrates are preferred luminal nutrients of the colonic mucosa. Starvation of colonocytes through lack or impaired metabolism of luminal SCFAs may be a cofactor in the pathogenesis of ulcerative colitis. DESIGN: A detailed histological evaluation of colonic biopsy specimens was performed in patients with active distal ulcerative colitis who were treated with rectal enemas containing a mixture of SCFAs, n-butyrate alone or saline placebo. Together with light microscopic parameters of mucosal inflammation, the pattern of crypt cell proliferation (proliferating cell nuclear antigen) and the mucosal activity of factor XIII were assessed. RESULTS: Butyrate reduced the density of polymorphonuclear leucocytes in the lamina propria (4 weeks: P = 0.063; 8 weeks: P = 0.091); other inflammatory parameters remained unchanged. Both butyrate and the SCFA mixture reduced significantly the number of proliferating cells in the upper 40% of crypts. Tissue factor XIII activity in active ulcerative colitis was significantly lower than in mucosa from normal colons; however, it was not affected by SCFA or butyrate irrigation. CONCLUSION: SCFAs and butyrate have a more marked effect on crypt cell proliferation than on parameters of inflammation in patients with active ulcerative colitis.

Adult↗
PubMed1996

New method of nuclear grading of tissue sections by means of digital image analysis with prognostic significance for node-negative breast cancer patients.

To optimize treatment of the individual patient with node-negative breast cancer, objective, reproducible, and standardized prognostic criteria are required. A number of factors have been studied in recent years, but until now it has been possible to obtain information about the risk of recurrence only for some patients belonging to subgroups with special characteristics. We report the establishment of an image analysis method for nuclear grading as an attempt to solve this problem. In a retrospective analysis, we used routine hematoxylin and eosinstained paraffin sections from 54 node-negative patients with surgery between 1980 and 1985. Cell scenes of primary tumors were scanned in a light microscope in successive focus positions to obtain three-dimensional information. After automatic image segmentation, nuclear features were calculated as input for a first binary classification tree to differentiate between tumor and nontumor cells. Tumor nuclei from patients with or without relapse were defined as high-risk or low-risk nuclei, respectively, and were separated with a second tree. Feature values of the measured tumor nuclei from each patient were examined with this second tree to analyze whether the majority of nuclei for each patient were classified as high-risk or low-risk nuclei. Correct classification rates in the two binary cell classification trees were 88.0% and 83.8%, respectively. In the learning sample of our study, all patients with a relapse had the majority of nuclei in the high-risk group, most with more than 80%. Therefore, it seems to be possible to develop an image analytical risk profile system for nuclear grading to provide information on individual prognosis.

Algorithms↗
PubMed1996

Glutathione reductase and glutamate dehydrogenase of Plasmodium falciparum, the causative agent of tropical malaria.

The use of glutathione reductase inhibitors in chemotherapy is the raison d'être for this study. Two enzymes were purified to homogeneity from the intraerythrocytic malarial parasite Plasmodium falciparum: glutathione disulfide reductase, an antioxidative enzyme, which appears to play an essential role for parasite growth and differentiation, and glutamate dehydrogenase, an enzyme not occurring in the host erythrocyte. The two proteins were copurified and separated by gel electrophoresis with yields of approximately 20%. Malarial glutathione reductase, a homodimer of 110 kDa with a pH optimum of 6.8 and a high preference for NADPH over NADH, was shown to contain FAD as its prosthetic group. The N-terminal sequence, VYDLIVIGGGSGGMA, which can be aligned with residues 20-34 of human glutathione reductase, represents the first beta strand and the diphosphate-fixing helix of the FAD domain. Glutamate dehydrogenase was confirmed as a hexamer with blocked N-termini; it is an enzyme that is highly specific for NADP and NADPH. The copurification of the proteins and the potential of P.falciparum glutathione reductase as a drug target are discussed.

Amino Acid Sequence↗
PubMed1996

Nature and sequence of simian immunodeficiency virus-induced central nervous system lesions: a kinetic study.

To determine the onsets and specificities of neuropathological features observed after simian immunodeficiency virus (SIV) infection of macaques, brains of 19 clinically unaffected rhesus monkeys (group A) were examined after intervals ranging from 1 to 48 weeks post-infection and compared to 8 animals with AIDS (group B) as well as to 8 uninfected controls. Based on morphological and virological parameters, seven patterns specific for SIV infection of the central nervous system (CNS) were discerned. In both groups of infected but not control animals, we found mononuclear aggregates in meninges, perivascular space, and choroid plexus stroma (designated pattern 1), isolated infected cells within CNS parenchyma (pattern 2), axonal degeneration (pattern 3), spongy change (pattern 4), microglial proliferation (pattern 5), and small vessel proliferation (pattern 6). SIV encephalitis (pattern 7) was only evident in animals with clinically evident disease. Changes characteristic of patterns 3, 5 and 6 appeared to be chronic and non-progressive, whereas lesions of patterns 1, 2 and 4 appeared to have progressed in animals with AIDS. The main component of mononuclear aggregates in animals of group A were lymphocytes, in contrast to animals of group B, in which macrophages dominated the inflammatory infiltrates. Altogether, our results demonstrate that subtle leukoencephalopathy was a specific feature of clinically silent as well as clinically evident phases of SIV infection. This might explain the neurological impairment of HIV-positive non-AIDS individuals.

Animals↗
PubMed1994

Vaginal clear cell carcinoma in a young patient with ectopic termination of the left ureter in the vagina.

The association of clear cell adenocarcinoma of the vagina and vaginal adenosis with prenatal exposure to diethylstilbestrol (DES) is well-documented in the United States. In Europe, however, DES was never used in the therapy of threatened abortion and, therefore, clear cell adenocarcinoma and vaginal adenosis remained rare diseases. We report on the clinical and pathological features of a case of clear cell adenocarcinoma of the upper vagina in a 17-year-old German girl, who had a history of hypoplasia of the left kidney with an ectopic termination of the ureter in the upper vagina, removed surgically 2 years before. No previous report of a similar coincidence of vaginal clear cell carcinoma and a congenital disorder of the genitourinary tract exists. Congenital anomaly of the ureter interfering with the development and the differentiation of the distal Müllerian tract and its epithelium might have provided a similar histological basis for carcinogenesis in our patient to that in those provided exposed to DES.

Adenocarcinoma, Clear Cell↗
PubMed1994

DNA-ploidy, G2M-fractions and prognosis of stages B and C prostate carcinoma.

Paraffin embedded tissue of 49 stage C and 27 stage B prostate adenocarcinomas was investigated by flow cytometry. All patients were treated by radical prostatectomy with pelvic lymphadenectomy and followed up for 5-10 years. The tumour was separated from the benign tissue to increase the proportion of tumour cells. Ten stage C and seven stage B carcinomas had to be excluded because of poor fixation. Six of the 39 (15%) stage C and 1/20 (5%) stage B carcinomas were aneuploid. Cell cycle analysis was done with correction for sliced nuclei and background subtraction. The threshold between carcinomas with low and with increased ("tetraploid") G2M-fraction was determined by comparing carcinomas with and without tumour progression. Sixty-seven percent of the patients with non-euploid stage C carcinomas and 11% of those with euploid carcinomas suffered from tumour progression (P < 0.01). The respective values for the stage B carcinomas were 67% and 6% (P < 0.01). These results demonstrate the strong prognostic impact of DNA-ploidy and G2M-fractions for each individual patient.

Adult↗
PubMed1994

[Correlation of organ pathology and distribution of virus replicating cells, demonstrated with RNA in situ hybridization of SIVmac infection of Macaca mulatta].

22 juvenile rhesus macaques were infected i.v. with SIVmac and killed at defined timepoints after infection. Productively infected cells were detected by RNA in situ hybridization in the paraffin material. Their number was correlated with the pathology of lymph nodes, thymus, extranodal lymphatic parenchyma and other organs. In the first weeks all lymphatic tissues and compartments got infected, as well as the brain, the bone marrow and other organs. The high virus replication during this first phase disappeared with the onset of the seroconversion and remained low during all stages of atrophy of the lymphatic parenchyma. The atrophy of the lymphatic parenchyma and its microenvironment was not correlated with virus replication. This may implicate that a virostatic therapy might be more successful in the first weeks of infection.

Animals↗
PubMed1994

[Immunity to diphtheria of African guest workers and students].

This study investigated the immuno-protective diphtheria antitoxin titres of 38 guest workers from Mozambique and 44 students from Cameroon 18 to 35 years of age. Two methods were used to analyse the sera: the cell culture method and the indirect haemagglutination test. The results of both methods were comparable. Approximately 69% of the guest workers from Mozambique showed protective diphtheria antitoxin levels (> or = 0.1 IE/ml), 24% had a boosterrequiring basic immunity (> or = 0.01-0.09 IE/ml), whereas 7% showed no protective diphtheria antitoxin levels. This compared with 46, 35 and 19% respectively among the students from Cameroon.

Adolescent↗
PubMed1993

Glutathione reductase in human and murine lung tumors: high levels of mRNA and enzymatic activity.

The enzyme glutathione reductase (GR) (GSSG+NADPH+H+-->2 GSH+NADP+) plays a key role in the cellular defense against oxidative stress. High levels of GR activity are often associated with tumor growth and/or resistance mechanisms against drug and radiation therapy. In order to investigate the molecular basis of elevated glutathione reductase activities we studied the enzyme at the DNA, mRNA and protein levels in murine experimental tumor cell lines and in human lung tumors. A modified ultracentrifugation procedure was developed which allowed the simultaneous isolation of DNA and total cellular RNA. Out of 11 human bronchial carcinomas obtained from patients without prior chemotherapy, five tumors showed a GR activity which was 2.4 to 3.8 times higher than in the respective control tissues. In each case the elevated enzyme activity was accompanied by an elevated GRmRNA levels. For none of the tumors, GR gene rearrangement or amplification was observed by Southern blot analyses. The mouse tumor cell lines ASB XIV, Lewis lung carcinoma and EAT cells, also showed high levels of GRmRNA whereas this mRNA was hardly detectable in normal mouse lung tissue.

Animals↗
PubMed1993

Alterations of thymus cortical epithelium and interdigitating dendritic cells but no increase of thymocyte cell death in the early course of simian immunodeficiency virus infection.

The role of the thymus in the pathogenesis of simian acquired immunodeficiency syndrome was investigated in 18 juvenile rhesus monkeys (Macaca mulatta). The thymus was infected from the first week post-SIVmac inoculation, but the amount of virus-positive cells was very low (< 1 in 10(4) T cells) as demonstrated by polymerase chain reaction and in situ hybridization. First morphological alteration was a narrowing of the cortex at 12 and 24 wpi. Morphometry revealed no increase of pyknotic T cells but a decrease of the proliferation rate and flow cytometry showed a reduction of the immature CD4+/CD8+ double-positive T cells. Ultrastructural analysis revealed vacuolization, shrinkage, and finally cytolysis of the cortical epithelial cells and the interdigitating dendritic cells. Immunofluorescence staining exhibited a widespread loss of cortical epithelial cells. This damage to the thymic microenvironment could explain the breakdown of the intrathymic T cell proliferation. It preceded fully developed simian acquired immunodeficiency syndrome and is therefore considered to play a major role in its pathogenesis.

Animals↗
PubMed1991

[Morphological alterations of lymph nodes and thymus during the early course of SIV infection of rhesus monkeys].

Rhesus monkeys (M. mulatta) were i.v. infected with SIV mac251. Three phases of lymph node changes were observed. 1: physiological follicular hyperplasia (3 and 6 weeks p.i.). 2: Alterations of germinal centers: loss of follicular mantle zone, fragmentation or sclerosis (12 and 24 weeks p.i.). 3: Partial depletion of T-lymphocytes, accumulation of plasma cells, increased numbers of syncytial giant cells, hemophgocytosis in the sinuses (about 1 year p.i.). The thymus of the juvenile animals showed first changes 12 and 24 weeks after infection with focal loss of immature (and Ki-67 positive) cortical thymocytes, leading to severe accidental involution of the thymuses one year after infection and reduced numbers of Hassalls corpuscles. These investigations show the value of this animal model for the study of morphology and pathogenesis of AIDS.

Animals↗