PubMed Health⌕ Search

Biomedical subjects

U Kaiser

Publications and source records attributed to U Kaiser.

At least 55 records · Page 3Linked to original sources

Glucocorticoid receptors and growth inhibitory effects of dexamethasone in human lung cancer cell lines.

Expression of glucocorticoid receptors (GR) and growth effects of dexamethasone and the antiglucocorticoid RU-486 were investigated in six cell lines originating from small cell lung cancer (SCLC) and 13 cell lines from non-small cell lung cancer (NSCLC; four adenocarcinoma, four squamous cell carcinoma, four large cell carcinoma and one mesothelioma). All cell lines contained specific and saturable binding sites for the synthetic glucocorticoid dexamethasone, as determined by whole cell assays and by cytosolic receptor assays. The presence of GRs in the carcinoma cells was confirmed by immunocytochemistry. In NSCLC cell lines, GRs were present in large amounts (37-638 fmol/mg cytosolic protein). In SCLC cell lines, GRs were also detectable but in considerably lower concentrations. Growth inhibitory effects of dexamethasone were seen in the cultures of two squamous cell carcinoma lines (EPLC-32M1 and NCI-H157), one adenocarcinoma line (A-549), one large cell carcinoma cell line (LCLC-97TM1) and the cell line of a mesothelioma (MSTO-211H). All cell lines responsive to dexamethasone had high GR concentrations (> or = 164 fmol/mg cytosolic protein). The antiglucocorticoid RU-486 was virtually inactive when administered alone but was able to block the growth-inhibitory effect of dexamethasone. The results indicate that glucocorticoids may inhibit the progression of individual non-small cell lung carcinoma.

Antineoplastic Agents, Hormonal↗

The DNA and steroid binding domains of the glucocorticoid receptor are not altered in mononuclear cells of treated CLL patients.

The aim of this study was to investigate whether mutations in the glucocorticoid receptor could account for the increasing unresponsiveness of patients with chronic lymphatic leukemia (CLL) to combination chemotherapy. The receptor was tested immunocytochemically, in steroid binding assays, and by a mutation screening (denaturing gradient gel electrophoresis) of the receptor-cDNA. The receptor concentration, as measured by staining and steroid binding test, varied considerably but showed no clear correlation to clinical response. Using a highly sensitive mutation screening assay of the DNA- and the steroid-binding region, none of the treated patients revealed any mutation, suggesting that the glucocorticoid receptor in the CLL patients tested is not altered in these domains. In one individual who had not been treated before analysis a silent mutation was found in one receptor allele. The results suggest that mechanisms other than altered ligand or DNA binding of the receptor may be responsible for the lack of response to chemotherapy. This conclusion is discussed in relation to the mechanism of corticoid resistance in mouse and human lymphoma cells in culture.

Animals↗

Generalised giant-cell tumour of bone: successful treatment of pulmonary metastases with interferon alpha, a case report.

We report on a 37-year-old female patient with generalised giant-cell tumour of the bone, whose tumour was refractory to conventional chemotherapy. Subsequent treatment with interferon alpha 2a in increasing dosage from 4 x 10(6) IU (three times a week) to 9 x 10(6) IU (three times a week) led to a significant decrease of pulmonary metastases and a stabilisation of the disease after 12 months of treatment. In progressive chemotherapy refractory giant-cell tumour interferon alpha 2a may be of therapeutic benefit.

Adult↗

Expression of insulin-like growth factor receptors I and II in normal human lung and in lung cancer.

Insulin-like growth factors are potent mitogenic factors in human lung cancer in vitro, acting via specific receptors. Using monoclonal antibodies we demonstrate the expression of insulin-like growth factor receptor I in bronchial epithelial cells of normal lung and in primary lung cancer (22/24 cases), being most prominent in squamous cell carcinoma. Electron microscopy on lung cancer cell lines reveals a distinct reaction pattern on the plasma membrane. Immunoreaction with a specific antibody directed against the insulin-like growth factor receptor II suggests a weak expression in primary lung cancer. Our findings underline the significance of the autocrine pathway of insulin-like growth factors in lung cancer.

Adenocarcinoma↗

New dimensions for the vital storage of microsurgical free flaps: an experimental approach.

A revolutionary circulatory system has been developed to nourish big, free osteomusculocutaneous flaps extracorporally. Thus we will be able to transplant the free flaps to defect areas that have no sufficient vascular situation. In respect to the cold storage of microsurgical free flaps, to date maximal periods of ischaemic tolerance have been considerably exceeded; the maximal period is currently 168 hours. The vitality of the flap is monitored through parameters setting forth the consumption of oxygen together with histology and electron microscopy. The oxygenation of the nutritive medium is achieved through an aqueous phase gas exchange.

Animals↗

Differential expression of insulin-like growth factor binding proteins in human non-small cell lung cancer cell lines.

The possible expression and secretion of insulin-like growth factor binding proteins (IGFBPs) by non-small cell lung cancer (NSCLC) cell lines was investigated and compared with possible IGFBP expression by primary NSCLC tumours. Cells growing under serum-free conditions released binding proteins with apparent molecular masses of 26-43 kD when analysed by a ligand blotting method under non-reducing conditions. Additionally, northern blot analysis of total RNA from NSCLC cell lines and tumours was performed using cDNAs coding for each of IGFBP-1, IGFBP-2, and IGFBP-3. This analysis revealed expression of all three mRNAs to varying degrees by all cell lines. In contrast all primary tumours analysed expressed predominantly IGFBP-2 and IGFBP-3 and none showed any evident expression of IGFBP-1. Both NSCLC cell lines and tumours synthesise IGFBPs but the pattern of expression differs significantly between cell lines and primary tumours.

Blotting, Northern↗

Monoclonal antipeptide antibodies to the glucocorticoid receptor.

The generation of monoclonal antibodies to synthetic peptides of the glucocorticoid receptor is described. Two antibodies to sequences from the DNA binding region are IgMs. Two other antibodies to sequences in the steroid binding region and the C-terminus belong to the IgG class. The specificity of the IgG binding to the receptor in an ELISA assay is demonstrated by competition with the relevant peptides. Both IgGs are able to recognize the receptor in Western blots, but do not form stable complexes in sucrose gradients. Steroid binding to the receptor is not influenced by preincubation with antibodies. This indicates that denaturation or distortion of the receptor is necessary for the accessibility of these antibodies to their epitopes. Both antibodies can be used to stain the glucocorticoid receptor in neoplastic cells of patients suffering from chronic lymphatic leukemia.

Animals↗

Felty's syndrome: favorable response to granulocyte-macrophage colony-stimulating factor in the acute phase.

We report a case of Felty's syndrome in which infectious complications due to severe neutropenia could be overcome by short-term treatment with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, 7 micrograms/kg/day s.c.). Leukocyte counts rose from 1,050/mm3 at presentation to 4,470/mm3 after 15 days of treatment. A flare-up of arthritis was not noted. Defects in granulocyte function and clinical improvement prior to leukocyte rise suggest that the beneficial effect of GM-CSF is mainly due to an improvement of granulocyte function.

Acute Disease↗

[Monosymptomatic endemic sprue as a cause of iron deficiency anemia].

For about two years a 23-year-old woman, without symptoms and of normal weight, had been known to have an iron deficiency anaemia (Hb 56 g/l; after oral iron substitution 100 g/l; mean corpuscular volume 66.7 fl, ferritin 5.0 micrograms/l). Gynaecological examination was normal. Radiography of the small intestine revealed coarse rugal pattern of the duodenum. Endoscopically obtained duodenal biopsy demonstrated villous atrophy. Elevated anti-gliadin antibody titres (IgG 49.9 U, IgA 52.3 U), as well as the response to a gluten-free diet confirmed the diagnosis of monosymptomatic coeliac disease. Although anaemia is one of the characteristic features of coeliac disease, it is rare as the only sign. The risk of delayed diagnosis is especially high in women before menopause.

Adult↗

Does the immunophenotype of renal cell carcinoma correlate with its clinical stage?

The following comparative study is an analysis of the clinical data, morphology and immunophenotype of 93 patients who have been operated on for renal cell carcinoma. We were able to show a close link between the histological grade and the occurrence of distant metastases: 33% of the patients with grade III tumours versus 11.5% of the patients with grade I tumours had developed metastasis by the time of the surgery. Histological subtyping per se did not give prognostic hints. Immunohistochemistry has revealed an inconsistent reaction pattern for the cytokeratin marker K11 (18/22). For proper diagnosis a panel of cytokeratin markers should be employed. The reaction patterns of monoclonal antibodies against the epidermal growth factor receptor (EGFR) and against myelomonocytic antigens in normal renal tissue (positive for the tubulus system) and in renal carcinoma indicate that renal cell carcinoma derive from the tubulus system. The proliferation marker Ki-67 correlates well with the histological grading. Although only a limited number of snap-frozen tumours have been investigated, this study indicates that EGFR is expressed by normal and by malignant renal tissue and that Ki-67 may serve as a prognostic marker.

Aged↗

B-cell lymphoma of the mucosa-associated lymphatic tissue (MALT) presenting with bone marrow and peripheral blood involvement.

A 46-year-old female patient was diagnosed as having a low-grade malignant B-cell lymphoma of the gastric MALT, stage IV, with bone marrow involvement and a leukaemic blood picture. Different from the infiltrate in the gastric mucosa, which consisted mainly of centrocyte-like cells, the leukaemic cells presented with a blood-picture resembling infectious mononucleosis but showing a predominance of plasma cells. Despite these cytological differences, a common clonal origin for both cellular compartments was demonstrated immunophenotypically and genotypically. Low-grade B-cell lymphomas of the MALT may thus initially present with stage IV disease and a leukaemic blood picture.

B-Lymphocytes↗

[Microbiological and morphological findings in reactive lymphadenopathy].

An attempt was made by means of microbiological and histomorphological methods for diagnostic elucidation of reactive lymphadenopathies in 52 patients. The serological findings differed from those recorded from clinically intact individuals, in that they included not only increased prevalence of antibodies but also increased antibody titres to cytomegalovirus, influenza virus, and toxoplasma gondii. The dynamic of antibody titres against antigens specific of herpesvirus, influenza virus, and toxoplasma gondii were followed up and enabled positive detection in 11 of 18 patients of active infections with the above pathogens involved. Histologically, the lymph nodes affected were characterised by alterations reminiscent to Piringer lymphadenitis. While, in the course of bacteriological investigations, various bacterial species were isolated from lymph node tissue of 35 patients, direct morphological identification from lymph node sections failed to work. Immature sinus histiocytosis and an increase in phagocytosis activity were among the typical tissue findings.

Adolescent↗

Duodenal somatostatinoma with psammoma bodies.

A duodenal somatostatinoma was found incidentally in a 60-year-old woman undergoing cholecystectomy. Microscopically, the tumor had a glandular architecture with abundant psammoma bodies. Electron microscopy revealed tumor cells resembling D-cells of the pancreatic islets. Immunohistochemically, there was staining for neuron-specific enolase, chromogranin, and diffuse cytoplasmic positivity for somatostatin only. By immunoelectron microscopy, somatostatin was identified predominantly in lucent membrane-bound secretory granules. X-ray-dispersive microanalysis showed the psammoma bodies contained calcium apatite crystals. This case is compared with other reported cases with a description of cellular localization of somatostatin and development of psammomatous calcification.

Adenoma, Islet Cell↗