[54-year-old patient with anemia, jaundice, hepatosplenomegaly and paravertebral space-occupying lesions].
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Anemia, Dyserythropoietic, Congenital↗
Biomedical subjects
R Munker
Publications and source records attributed to R Munker.
[Small cell prostatic carcinoma. Presentation of diagnosis, therapy and prognosis based on a case report].
On the basis of a case report, the particular features of the rare small-cell carcinoma of the prostate, which has much in common with, for example, small-cell lung cancer, are discussed. Diagnosis, treatment and course of the disease are presented. The primary therapeutic mode is not surgical removal but cytostatic chemotherapy. The results of large retrospective studies of case material are discussed.
Antineoplastic Combined Chemotherapy Protocols↗
[Expression of transforming growth factor beta-3 (TGF-beta-3) on reactive and malignant cells in ascites and pleural effusion].
PATIENTS AND METHOD: The expression of TGF-beta-3 was examined in 64 patients with reactive and malignant effusion by immunocytochemistry. RESULT: In about half of the patients with malignant effusions (especially breast cancer, gastric cancer, and carcinomas of unknown primary) TGF-beta positive tumor cells could be detected. We could show here for the first time that reactive mesothelial cells could also express TGF-beta. Lymphatic cells were negative in all cases. TGF-beta-3 bioactivity could also be detected in the effusions studied. In our group of patients with far advanced cancer, the expression of TGF-beta had no clear-cut clinical or prognostic correlate. However, the expression of TGF-beta on tumor cells should be interpreted as a marker of tumor progression, taking into account the fibrogenic, angiogenic and immunosuppressive properties of TGF-beta. CONCLUSION: Further research is necessary to answer the question if the 3 isoforms of TGF-beta are coordinately expressed and to elucidate the involvement of this cytokine in tumor progression and metastasis.
Adult↗
The two soluble forms of the lipopolysaccharide receptor, CD14: characterization and release by normal human monocytes.
CD14, a glycolipid-anchored membrane glycoprotein, acts as a high affinity lipopolysaccharide receptor on leukocytes. We previously reported that the Mono-Mac-6 cell line releases two different soluble forms of CD14 (sCD14) (Labeta et al., Eur. J. Immunol. 1993. 23: 2144). Here we show that the two sCD14, which we now refer to as sCD14 alpha (low M(r)) and sCD14 beta (high M(r)), are also synthesized and released by normal human monocytes and present in normal plasma. Their mechanism of release was examined by using the Mono-Mac-6 cell line, chinese hamster ovary cell (CHO)/CD14+ transfectants and plasma from paroxysmal nocturnal hemoglobinuria (PNH) patients. It was found that: (1) sCD14 beta is released faster than sCD14 alpha and that the release of the latter is a lengthy process. (2) Monensin blocked the biosynthesis of membrane-bound CD14 (mCD14) and sCD14, additionally, a 50-kDa CD14 polypeptide accumulated in the cell lysate, suggesting that the different forms of CD14 may have a common precursor. (3) Monensin also blocked the release of sCD14 alpha from surface-labeled cells, suggesting that conversion of mCD14 to sCD14 alpha involves a mechanism of endocytosis followed by exocytosis. Interestingly, (4) sCD14 alpha and sCD14 beta were detected in PNH plasma, indicating that sCD14 alpha may also derive from an endogenous pathway. (5) Phospholipase C-released CD14 was identical in size to mCD14, thus differed from sCD14 beta by approximately 2000, indicating that release of sCD14 beta involves further processing. (6) CHO cells transfected with a CD14 cDNA coding for an eight C-terminal amino acids shorter product released an sCD14 beta-like form; thus absence of the eight C-terminal amino acids prevented mCD14 expression but not the secretion of sCD14 beta. The characterization of sCD14 alpha and sCD14 beta reported here may be useful for better understanding of variations in sCD14 levels in pathological conditions and the contribution of each sCD14 in sepsis and other, as yet unknown functions.
Animals↗
Interaction between tumor necrosis factor-alpha and HSP 70 in human leukemia cells.
We confirm here by immunoblotting that a cell line resistant to clonal inhibition from tumor necrosis factor (K562) expresses high levels of HSP 70, whereas two sensitive cell lines (HL60 blast and EM3) express low levels. When sensitive cell lines are exposed to tumor necrosis factor, HSP 70 is not generally induced; when tumor necrosis factor is removed, however, HSP 70 is transiently induced. In five bone marrow samples from patients, generally low levels of HSP 70 were detected.
Blotting, Western↗
Effects of tumor necrosis-factor on primary human leukemia cells: ultrastructural changes.
We investigated the ultrastructural effects of recombinant tumor necrosis factor alpha (TNF) on primary leukemia cells of 8 patients (4 cases of acute myelogenous leukemia and 4 cases of chronic myelogenous leukemia) as well as on bone marrow cells of 1 normal control. The cells were kept in liquid culture for up to 92 h in the presence of up to 10,000 U/ml of recombinant human TNF without adding colony-stimulating factors. Under these conditions the concentration of viable leukemic cells decreased by 14 to 53%, compared to control cultures. In acute myelogenous leukemia, all cases to some degree developed an enlargement of mitochondria; in 2 cases prominent cytoplasmic processes, and in 2 cases cytoplasmic vacuoles were observed. In chronic myelogenous leukemia, an enlargement and deformation of all cell types was observed to varying degrees. In the normal bone marrow sample only minor cytoplasmic changes occurred. In all cultures apoptotic changes were rarely observed and--if present--were observed also in cultures without TNF. When the DNA of leukemic cells treated with TNF was separated on agarose, no fragments characteristic of apoptosis were visible. Our results demonstrate that TNF does not induce direct cytotoxicity or apoptosis in acute or chronic myeloid leukemias and are compatible with the notion that some leukemic cells may be activated or stimulated by TNF. The mitochondrion appears to be one of the primary targets of TNF. Electron microscopy is useful for monitoring the changes induced by TNF.
Apoptosis↗
TNF induces cytoplasmic vesicles in actinomycin D-treated K 562 cells.
We report here that tumor necrosis factor alpha (TNF) induces peculiar cytoplasmic vesicles in the human erythromyeloid leukemia cell line K 562, sensitized to the cytotoxic action of TNF by a treatment with the inhibitor of transcription actinomycin D. These vesicles are well delineated ultrastructurally. The formation of these vesicles is characteristic for the combination of actinomycin D with TNF and precedes the changes of apoptosis and cellular disintegration. These vesicles correspond to an intermediate step in the cytotoxicity caused by TNF and may indicate that reactive metabolites are involved in the mechanism of action of TNF.
Cell Division↗
[Graft versus host disease with fatal outcome after administration of filtered erythrocyte concentrates].
Transfusion-associated graft-versus-host disease (TA-GVHD) resulting from the engraftment of competent lymphocytes contained in blood products has been well described in immunocompromised patients and more recently in immunocompetent patients. Prophylactic irradiation of blood products prior to transfusion is the most efficient way to prevent TA-GVHD. Standard blood bank measures to reduce mononuclear cell contamination in red blood cell units, such as freezing, washing and filtration, may reduce the number of viable lymphocytes to prevent immunizations. However, it is unknown whether the depletion of leukocytes with these techniques would decrease the risk of TA-GVHD. In this report we describe the first case of TA-GVHD following transfusion of filtrated red blood cells given to a patient receiving cytotoxic therapy for Hodgkin's disease.
Adult↗
[Lennert's lymphoma and glomerulonephritis].
A 49-year-old man noticed a swelling below the left ear. The histological diagnosis was chronic lymphadenitis with a small cell epithelioid cell reaction. A short time later he developed oedema of the legs, proteinuria and elevated serum creatinine levels (1.89 mg/dl). Renal biopsy showed mesangioproliferative glomerulonephritis. Over the next two years the tumour in the left side of the neck gradually increased in size. Computed tomography showed a space-occupying lesion 5 x 7 cm in the vicinity of the left parotid gland, with evidence of infiltrative growth. Histological examination of the tumour after removal revealed epithelioid cell tissue with numerous lymphocytes, and led to the diagnosis of a lymphoepithelial lymphoma (Lennert's lymphoma), a T-cell lymphoma of low malignancy. Complete remission was achieved after four chemotherapy cycles (COPP schedule) in reduced doses (creatinine concentration 2.09 mg/dl, creatinine clearance 36 ml/min); creatinine clearance subsequently improved to 63 ml/min. Later, however, the tumour recurred and the patient went into terminal renal failure, dying four years after the lymphoma first appeared. The glomerulonephritis may conceivably have been a paraneoplastic phenomenon.
Antineoplastic Combined Chemotherapy Protocols↗
Serum androgens in intensive-care patients: correlations with clinical findings.
Serum androgen levels were studied in 100 patients (50 male) with varying degrees of severe illness, determined by Acute Physiological and Chronic Health Evaluation (APACHE). Comparison with normal subjects revealed the following changes: (1) Basal dehydroepiandrosterone sulphate (DHEAS) values were decreased in the ill female patients (P less than 0.001) as well as in the ill males (two groups, P less than 0.01; P less than 0.05). Androstenedione values did not differ from the controls in patients of either sex. Basal testosterone levels were decreased in ill male patients (P less than 0.001), but not in females. (2) The low testosterone concentrations in the severely ill male patients correlated inversely with the APACHE score; additionally, a dependence on diagnostic categories could be demonstrated in men, since the lowest values were found in patients suffering from sepsis or liver cirrhosis. Acutely ill males had a moderately decreased testosterone, whereas chronically ill males showed a marked reduction of testosterone compared to the controls. Lowered DHEAS and androstenedione levels could be measured in chronically ill males but not in ill females. (3) 17 alpha-OH-progesterone and 17 alpha-OH-pregnenolone levels in subgroups of the patients suggested a probable enzymatic block in the delta 5-pathway of androgen biosynthesis in severe illness. The ratio of 17 alpha-OH-pregnenolone to DHEAS was significantly higher in male patients and tended to be high in ill females, whereas the ratio of 17 alpha-OH-progesterone to androstenedione showed no difference between healthy and ill subjects.
17-alpha-Hydroxypregnenolone↗
Tumor necrosis factor: an update on basic research and clinical applications.
Tumor necrosis factor is one of the recently cloned cytokines with pleiotropic effects on normal and malignant cells. Our knowledge about the scope of cells producing or responding to this cytokine has enormously expanded. In critically ill patients with acute hepatic failure, acute graft-versus-host disease, or septic shock, circulating tumor necrosis factor can be measured and useful prognostic correlations do exist. Despite promising in vitro results, early clinical trials with tumor necrosis factor for the treatment of cancer have failed thus far to reveal major antineoplastic activity in cancer patients. However, more clinical trials are necessary, since different routes of administration and combinations with other cytokines may lead to favorable results.
Drug Evaluation↗
[Septic temperatures and throat pain in a patient with hyperthyroidism].
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Agranulocytosis↗
A Ph1 chromosome positive B cell line expresses the fusion protein P 210.
We established a B lymphocyte line from bone marrow cultures of a patient with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia. The cell line (MB) is positive for Ph1 and has the phenotype of mature B lymphocytes transformed by the Epstein-Barr virus (EBV). When DNA was isolated and hybridized to specific cDNA probes, a rearranged immunoglobulin gene and EBV-sequences were detected. On Western blots of cell extracts, the novel fusion protein (P 210) was demonstrated with antisera against bcr and v-abl proteins. These results confirm the concept that B lymphocytes in CML can be involved in the malignant clone and demonstrate that these B cells express the fusion protein.
Adult↗
Effect of recombinant monokines, lymphokines, and other agents on clonal proliferation of human lung cancer cell lines.
The modulation of clonal growth of cells of 15 human lung cancer lines was examined by coculture with different recombinant lymphokines, monokines, and several agents which induce differentiation in other malignant cell systems. Recombinant human tumor necrosis factor alpha (TNF) was inhibitory to all non-small cell lung cancer cell lines with a 50% effective dose of clonal inhibition (ED50) in the range of 30-2000 units/ml. Two representative squamous lines (SK-MES and P3) had 150 to 250 high affinity (Kd approximately equal to pM) cell surface TNF receptors. In contrast, clonal growth of small cell lung cancer lines was not inhibited by TNF, and two representative lines (H69c and R592) expressed negligible cell surface TNF receptors. Recombinant alpha, beta, and gamma interferons (4000 units/ml) each inhibited greater than or equal to 30% clonal growth of more than 50% of the non-small cell lung cancer lines. TNF (100-1000 units/ml) in combination with gamma-interferon was synergistic in the inhibition of clonal growth of these cells. Further studies showed that synergism of clonal inhibition occurred even when the cells were initially exposed to gamma-interferon, washed, and plated in soft agar with TNF. All-trans-retinoic acid (ED50, 5 X 10(-7)-10(-6) M), dimethyl sulfoxide (ED50, 1.2-1.6%), and 12-O-tetradecanoylphorbol-13-acetate (ED50, 5 X 10(-8)-10(-10) M) inhibited clonal proliferation of 7 of 9, 7 of 9, and 8 of 9 non-small cell lung cancer lines, respectively. In contrast, clonal proliferation of cells of small cell lung cancer lines was decreased only slightly at almost all concentrations of each of the agents. Interleukin-1 and -2 and granulocyte-monocyte colony-stimulating factor had no effect on the clonal growth of any of the lung cancer lines. Our results suggest that TNF in combination with gamma-interferon may be therapeutically active for some patients with non-small cell lung cancer, but small cell lung cancer probably will be unresponsive to all the agents that we examined.
Calcitriol↗
Tumor necrosis factor: recent advances.
Tumor necrosis factor is a protein secreted by activated monocytes. In addition to its known cytotoxic or cytostatic effect on some tumor cells, recently it was discovered to have multiple effects on normal cells. These effects include modulation of cell growth and function, production of growth factors, and induction of surface antigens. In this article we review some of the advances which were made since the gene for tumor necrosis factor was cloned.
Animals↗
In vitro action of tumor necrosis factor on myeloid leukemia cells.
We investigated the in vitro action of recombinant tumor necrosis factor alpha (TNF) on the clonal growth of normal and malignant myeloid cells. Clonogenic cells from six of nine myeloid leukemia cell lines were very sensitive to the effects of TNF with 50% of the colonies inhibited (ED50) by concentrations of TNF that ranged between 6 and 150 U/mL. A decrease in DNA, RNA, and protein synthesis and in cloning efficiency occurred within three hours of exposure of HL-60 promyelocytes to TNF. The TNF in combination with recombinant interferons produced an additive or synergistic inhibition of colony formation of HL-60 and THP-1 myelomonoblasts. Normal human CFU-GM are sensitive to TNF (ED50 between 100 and 50,000 U/mL), but their sensitivity to TNF depends on the source of colony stimulating factor (CSF) with T lymphocyte derived GM-CSF (recombinant or natural) partially protecting the CFU-GM from the suppression exerted by TNF (and interferons). In eight of 15 cases the clonogenic myeloid leukemia cells from patients with acute or chronic myeloid leukemia were more sensitive than normal CFU-GM using GM-CSF as a source of colony stimulating activity. Further studies showed that the action of TNF on myeloid leukemia cells probably can be only partially explained by differentiation. Our finding of a possible selective cytotoxicity to leukemic clonogenic cells by TNF suggests that TNF may have value in the therapy of some patients with myeloid leukemia.
Blast Crisis↗
Recombinant human TNF alpha stimulates production of granulocyte colony-stimulating factor.
Tumor necrosis factor alpha (TNF alpha) stimulates production of granulocyte colony-stimulating factor (G-CSF) protein and mRNA in fibroblast cells. In contrast, TNF beta is at least 1,000-fold less potent than TNF alpha in increasing levels of G-CSF and GM-CSF activity and mRNA. The fibroblasts produce G-CSF and GM-CSF mRNA in a coordinate fashion after exposure to TNF. The ability of TNF alpha to stimulate production of CSF in fibroblasts may be pivotal to regulation of hematopoiesis.
Adult↗
Flow cytometry of TPA-induced changes in cells of chronic B-cell leukemias.
Cells from 14 patients with chronic B cell leukemias were cultured for up to 7 days with TPA (160 nM) in order to induce maturation of the malignant cells. Five cellular parameters, which can be quantitated by flow cytometry were analyzed in such cultures. These parameters were cell size, cell cycle, RNA, neutral esterase activity and dye uptake in mitochondria. Cell size increased in 13/14 cases in TPA treated cells compared to control cells. Cell cycle analysis revealed a low percentage of cells in S and G2/M phase both in control and TPA-treated cultures of chronic B cell leukemias, while in cultures of peripheral blood mononuclear cells TPA caused a large increase of S and G2/M cells. Both in chronic B cell leukemias and in PBMC, TPA induced an increase of RNA staining and neutral esterase activity in all or most cultures. Furthermore the staining of mitochondria increased in most cases. In conclusion, multiple changes can be induced by TPA in chronic B cell leukemias without associated proliferation.
Adult↗