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Biomedical subjects

R Herrmann

Publications and source records attributed to R Herrmann.

At least 145 records · Page 8Linked to original sources
PubMed1994

[Hepatocellular carcinoma: systemic chemotherapy, perspectives of gene or immunotherapy].

The systemic chemotherapy of hepatocellular carcinoma with single agent or combination chemotherapy has not resulted in reproducible response rates above 20%. Correspondingly, an effect on the survival of the treated patient population has not been shown so far. The most effective single agent is doxorubicin, which should, however, not be used outside of clinical studies in the systemic treatment of hepatocellular carcinoma. The results of hormonal treatment of hepatocellular carcinoma are also disappointing: the response rates of agents like tamoxifen, ketoconazol, nilutamid, LHRH-agonists or megestrol are usually below 10% and the survival of patients can not be improved. New approaches that are currently tested in vitro and in mouse models are pharmacological or immunological interactions with tumor cells that make use of molecular biology techniques and are summarised under the term "gene therapy". Some of these projects are in clinical phase I studies and first results can be expected in the next three to five years.

Antineoplastic Agents↗
PubMed1994

[Bioequivalence of a new tablet formulation of sotalol hydrochloride in comparison to a standard preparations].

Bioequivalence of a New Sotalol Hydrochloride Tablet Formulation Compared with a Standard Preparation An investigation on the bioavailability of a new tablet with 80 mg sotalol hydrochloride (Rentibloc mite, CAS 959-24-0) was performed in a two-way cross-over study with 16 persons. The relative bioavailability with respect to a reference preparation for AUC0-infinity was 101.9% and for Cmax 104.5%. A positive decision for bioequivalence derived from the usual confidence intervals for both parameters. The difference in tmax showed no clinical relevance. The new formulation is bioequivalent to the reference.

Adult↗
PubMed1993

Codon reading scheme in Mycoplasma pneumoniae revealed by the analysis of the complete set of tRNA genes.

The 33 genes encoding the complete set of tRNA species in Mycoplasma pneumoniae have been cloned and sequenced. They are organized into 5 clusters in addition to 9 single genes. No redundant gene was found, indicating that 33 tRNAs correspond to 32 different anticodons and decode all 62 codons used in this organism. There is only one single tRNA for each of the Ala, Leu, Pro, and Val family boxes. Therefore, a simplified decoding system resembling that recently described for Mycoplasma capricolum (1) has to also exist in M.pneumoniae. However, analysis of the anticodon set and codon usage revealed features characteristic of the latter: (i) there is no obvious preference toward AT rich synonymous codons, (ii) CGG codons are assigned for arginine and are translated by tRNA Arg(UCG), and (iii) CNN or GNN anticodons are encountered in the Ser, Thr, Arg, and Gly family boxes. We thus propose that this codon-anticodon recognition pattern has emerged in the 'M.pneumoniae cluster' under a genomic economization strategy but without the influence of AT pressure.

Amino Acid Sequence↗
PubMed1993

[Chemotherapy of esophageal carcinoma].

In metastatic esophageal cancer, single agent or combination chemotherapy induces short remissions in only a minority of patients. Therefore, only selected patients should be treated. More than half of patients with locoregional disease will experience significant improvement through cisplatinum-based combination chemotherapy. However, this has so far not shown itself to influence overall survivaL. Combination chemo-radiotherapy is superior to radiotherapy alone in locoregional disease. Studies in operable esophageal cancer comparing chemo-radiotherapy with surgery alone have not so far been reported.

Antineoplastic Agents↗
PubMed1993

Release from a human monocyte-like cell line of two different soluble forms of the lipopolysaccharide receptor, CD14.

Lipopolysaccharide (LPS) stimulates mononuclear phagocytes to synthesize and secrete immunoregulatory and inflammatory molecules such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-alpha). LPS forms complexes with either the serum protein termed LPS-binding protein or a serum factor, septin. These complexes are more stimulatory than LPS alone. The myeloid differentiation antigen CD14 is known to be the receptor for such complexes. In the present study, by using a monocytic cell line, we demonstrate the release of two different soluble forms of CD14 (sCD14) which are secreted by different mechanisms. We show that the two sCD14 forms differ in their electrophoretic mobility, two-dimensional gel electrophoretic patterns, sensitivity to endoglycosidases and peptide maps. One of the sCD14 molecules, apparent molecular mass 48 kDa, was found in supernatants of both surface iodinated and [35S]methionine biosynthetically labeled cells. The other sCD14 molecule (56 kDa) was found labeled only in supernatants of [35S]methionine-labeled cells. Furthermore, purified 48 kDa sCD14 enhanced the LPS-induced TNF-alpha and IL-6 release by the monocytic cells suggesting that a cell-surface signal transducer molecule may be involved in signaling. The data suggest a possible novel role for sCD14 in the monocyte response to LPS.

Antigens, CD↗
PubMed1993

Weight loss in patients with hematological neoplasias is associated with immune system stimulation.

Weight loss is the main symptom of so-called tumor cachexia. The pathogenetic mechanisms underlying cachexia are poorly understood; however, it appears that enhanced formation of cytokines such as interferon-gamma and tumor necrosis factor-alpha are involved. In 94 patients suffering from hematological neoplasias we compared body weight changes with serum neopterin, tryptophan, and kynurenine. Biochemical changes, the formation of neopterin, the degradation of tryptophan are closely related to interferon-gamma activity. The majority of our patients had increased neopterin and decreased tryptophan concentrations. Weight loss was seen particularly in patients with higher neopterin and lower tryptophan values. An association between higher neopterin levels and greater weight loss was apparent at study entry and during the follow-up of patients. Our data support the concept that weight loss is closely linked to endogenous interferon-gamma activity.

Biomarkers↗
PubMed1993

Serum soluble tumour necrosis factor receptor 55 is increased in patients with haematological neoplasias and is associated with immune activation and weight loss.

Enhanced concentrations of soluble forms of the receptor for tumour necrosis factor (TNF)-alpha have been detected in the serum of cancer patients. We determined serum concentrations of soluble TNF receptor p55 (sTNF-R55) in patients with haematological neoplasias, 50 patients suffering from non-Hodgkin's lymphoma (n = 35), Hodgkin's disease (n = 10) and multiple myeloma (n = 5). Compared with healthy controls and with patients with potential thyroid disease, significantly elevated concentrations of sTNF-R55 were found (mean +/- standard error: 2.68 +/- 0.22 vs. 1.23 +/- 0.21 ng/ml, P < 0.0001 and 2.18 +/- 0.32 ng/ml, P = 0.03). Likewise, neopterin concentrations were raised (19.6 +/- 3.66 vs. 5.3 +/- 0.25 nmol/l in controls, P < 0.0001). We found a significant correlation between sTNF-R55 and neopterin concentrations (Rs = 0.544, P < 0.001). Patients with weight loss showed higher sTNF-R55 concentrations than patients with stable weight. Our results confirm the relevance of sTNF-R55 concentrations in serum of patients with cancer.

Biopterins↗
PubMed1993

Fertility after ectopic pregnancy.

OBJECTIVES: To compare pregnancy rates (PRs) after radical or conservative surgical treatment for tubal pregnancy over a 12.5-year interval (minimum of 3 years) and to assess the relative contribution of various risk factors to future fertility performance. DESIGN: A retrospective cohort study examining the influence of various risk factors on PRs with stepwise discriminant analysis using a jackknife-type validation program. PATIENTS: Eighty-eight Olmsted County, Minnesota, women who presented over a 10-year interval with their first ectopic pregnancy (EP), undergoing either radical or conservative surgery at laparotomy, who actively attempted conception after surgery and who were available for follow-up at Mayo Clinic. MAIN OUTCOME MEASURES: The primary end point for analysis was the occurrence of a livebirth or EP at 3 years of follow-up after the index EP. RESULTS: No difference in PR was identified in patients treated with radical or conservative surgery. Patients who underwent conservative surgery had a higher risk of subsequent EP. Patients with a prior history of infertility had significantly reduced fertility potential. CONCLUSIONS: Prior history of infertility was the most significant determinant for fertility potential after surgical treatment for EP. Patients with prior infertility had markedly impaired fertility after surgical treatment of EP, and outcome was not influenced by choice of surgical procedures. Patients without prior infertility had comparable encouraging fertility potential with both conservative and radical therapy. These findings have relevance for future management of infertility in affected patients.

Discriminant Analysis↗
PubMed1993

Molecular alterations in a patient with Turcot's syndrome.

Cells of a patient with Turcot's syndrome and of her parents were evaluated for the presence of molecular alterations in the p53 and the Ki-ras gene. Deletions on chromosome 17p, overexpression and point mutations of the p53 gene as well as mutations of the Ki-ras gene were detected in primary and metastatic tumour but not in the germline of the patient nor in her parents.

Adenocarcinoma↗
PubMed1993

[Oncology 1992. Association with ophthalmology and brief status evaluation].

Several clinical situations require the cooperation of ophthalmologist and medical oncologist. Systemic metastasis spreading from an ocular primary tumor may rarely pose a problem. Liver metastasis from an ocular melanoma can be treated with intrahepatic chemoembolization and local palliation can be achieved. Disseminated tumors such as breast cancer or leukemias may spread to the eye and require local therapy. Per continuitatem orbital infiltrations of i.e. nasopharyngeal carcinomas need a cooperative management. Ocular side effects from chemo/radiotherapy may be especially severe in high dose therapies such as preparative regimes for allogeneic bone marrow transplants (BMT). A Sjögren-type sicca syndrome, cataracts and a microvasculopathy with cotton wool spots are associated with total body irradiation and the immunosuppression needed in BMT. Cancer research over the past ten years was increasingly influenced by molecular biology which has added to our understanding of tumor biology. The retinoblastoma gene is a typical example of a tumor suppressor gene. It regulates cell growth in its normal physiological state. Deletions may occur, that lead to tumor formation. The detection of oncogenes helps in the diagnosis of leukemias or lymphomas. Growth factors such as the Granulocyte Colony Stimulating Factor (G-CSF) were introduced recently. The differentiation therapy with retinoids has brought a new dimension into the field of cancer treatment and probably also of cancer prophylaxis. Taxol, an alkaloid from the yew tree is a novel cytostatic compound with very promising activity in tumors such as refractory ovarian or breast cancer. High dose therapy with BMT today is an established treatment for certain leukemias.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Modality Therapy↗
PubMed1993

Altered expression of the retinoblastoma susceptibility gene in chronic lymphocytic leukaemia.

The pathogenesis of chronic lymphocytic leukaemia (CLL) is unknown. One of the most frequent cytogenetic abnormalities in CLL is a deletion within the long arm of chromosome 13, the region to which the retinoblastoma (Rb) gene has been mapped. Lack of Rb expression has been linked to the carcinogenic process in many human tumours. We therefore sought to investigate the role of Rb gene inactivation in CLL using differential polymerase chain reaction on reverse transcribed RNA. The result of the PCR was quantitated using HPLC. 5/39 patients revealed a lack or significantly impaired expression of the Rb gene upon differential PCR analysis. In addition, immunocytochemical studies were performed using the Rb-specific monoclonal antibody PMG245. 10/56 patients showed a weak or absent expression upon immunocytochemical analysis compared to monocytes or granulocytes. The samples lacking Rb were from both early and late stage CLL. Our results indicate that inactivation of the Rb protein occurs in a fraction of CLL cases and can be found in early and late stages of the disease.

Aged↗
PubMed1993

Very early analysis of graft establishment after allogeneic bone marrow transplantation using the polymerase chain reaction.

We have used minisatellite polymorphisms flanking the apolipoprotein B locus and PCR to demonstrate the emergence of donor specific alleles in peripheral blood at 3-7 d post allogeneic bone marrow transplantation (BMT). This technique affords a very early indication of the establishment of stable engraftment, and may identify patients at risk of graft failure or leukaemic relapse. Patterns of T-cell chimaerism in the first 7-14 d following transplantation may be closely associated with the development of graft-versus-host disease (GVHD), the graft versus leukaemia (GVL) effect and graft rejection and future application of this technique to the investigation of early T-cell chimaerism may give further insights into these immunologically mediated events.

Alleles↗
PubMed1993

Recombinant human erythropoietin in patients with myelodysplastic syndrome and myelofibrosis.

In a dose titration study we tested the efficacy and tolerance of recombinant human erythropoietin (rhEPO) in 10 patients with myelodysplasia (MDS) and 2 patients with idiopathic myelofibrosis. Patients with a haemoglobin level < 100 g/l were treated as out-patients for 12 weeks with daily doses ranging from 30 U/kg body weight (BW) up to 240 U/kg BW in non-responders. Of the 10 patients with MDS, 6 were suffering from refractory anaemia with sideroblasts (RAS) and 4 from refractory anaemia with an excess of blasts. The median age was 73 years (range 41-81). Two patients with RAS responded with a rise in haemoglobin concentration to > 130 g/l. They had not been transfusion-dependent prior to treatment. Both patients had relatively low serum concentrations of immunoreactive EPO. There was neither a rise in haemoglobin nor a reduction in transfusion dependence in any of the other patients. It may be concluded that rhEPO is possibly effective in a subgroup of MDS patients where the disease is less advanced. None of the transfusion-dependent patients benefited.

Adult↗
PubMed1993

Position specificity of Ki-ras oncogene mutations during the progression of colorectal carcinoma.

The Ki-ras proto-oncogene is converted into an active oncogene by mutations in codon 12, 13, or 61. The incidence of mutations in the Ki-ras oncogene in colorectal adenomas and primary colorectal carcinomas has been shown to be 50-75 and 40-65%, respectively. To determine the role activation of the Ki-ras oncogene plays in the progression of colorectal carcinoma, we analyzed DNA from 11 nude-mouse xenografts and from 24 metastases of 22 patients with colorectal carcinoma, using the polymerase chain reaction technique and hybridization with labeled mutation-specific oligomers. Eleven of the 24 metastases (46%) carried mutations, 7 in codon 12 and 4 in codon 13, whereas only 1 nude-mouse tumor (9%) harbored a Ki-ras codon-12 mutation. Eleven of these 12 mutations in advanced stages of colorectal cancer were localized to the second position of either codon 12 or codon 13, whereas a majority of published ras mutations in earlier stages are in the first position of codon 12 of the Ki-ras oncogene. We conclude that there is a position specificity of Ki-ras oncogene mutations in advanced stages of colorectal carcinoma. In general, however, these mutations do not seem to play an important role in the progression of this cancer.

Amino Acid Sequence↗
PubMed1993

Testosterone-induced compared with oestradiol-induced immunosuppression against Plasmodium chabaudi malaria.

Testosterone suppresses immunity against malaria caused by Plasmodium chabaudi in B10 mice. Since this effect is probably not mediated through the classical androgen-receptor response, we investigated whether testosterone might act, after aromatization to oestradiol (OE2), through the oestrogen receptor (ER). Indeed, OE2 was found to act immunosuppressively when used at only about 1% of the immunosuppressive dose of testosterone. This becomes evident as an OE2-induced suppression of self-healing of P. chabaudi infections in female and castrated male B10 mice. The immunosuppressive OE2 effect is associated with a 16-fold increase in the circulating level of OE2 and can be prevented by ER blockers such as tamoxifen and clomifene. In contrast, the immunosuppressive effect of testosterone, which is not associated with any changes in the level of OE2, cannot be abolished by ER blockers or by aromatase inhibitors, such as atamestane and drofazar hydrochloride. Moreover, OE2 and testosterone act differently on spleen cells; OE2 induces a decrease in CD(4+)-T-cells, whereas testosterone causes an increase in CD(8+)-T-cells and a decrease in total nucleated spleen cells. The immunosuppressive effect of testosterone, but not that of OE2, can be adoptively transferred to syngeneic mice by nucleated spleen cells, predominantly T-cells. Our data show that the immunosuppressive activity of testosterone, in contrast to OE2, is not mediated through the ER. The immunosuppressive action of testosterone is therefore thought to be primarily mediated through a non-genomic mechanism.

Animals↗
PubMed1993

CD14 and tolerance to lipopolysaccharide: biochemical and functional analysis.

To evaluate the role of the high-affinity monocyte receptor for lipopolysaccharide (LPS), CD14, in the process of tolerance to LPS, the human monocytic cell line Mono-Mac-6 was cultured in the absence or presence of different amounts of LPS. The kinetics of CD14 modulation in these cells showed an initial 4-day period characterized by increased cell-surface expression, rate of biosynthesis (peaking at 48 hr) and release of its soluble forms (sCD14) which correlated with the amount of LPS in the culture. At this time, tolerance to LPS was already established, as measured by tumour necrosis factor-alpha (TNF-alpha) induction, it was LPS dose dependent and persisted up to 15 days. LPS also reduced the cell proliferation rate in a dose-dependent manner. After 8 days and up to 15 days, the CD14 biosynthesis, cell-surface expression and release of sCD14 inversely correlated with the level of LPS in the culture. The 48-hr LPS-pretreated cells showed a slightly decreased CD14 affinity for LPS, a relative high number of CD14 molecules per cells, and desensitization also to a phorbol 12-myristate 13-acetate (PMA) challenge. An anti-CD14 monoclonal antibody (mAb) protected the cells from tolerization when added at the beginning of culture, as revealed by challenge with LPS and PMA. The data indicate that in this model tolerization to LPS (1) precedes CD14 down-modulation, (2) operates by alteration of the receptor affinity for LPS and by a mechanism which affects a protein kinase C (PKC)-dependent signalling pathway, and (3) that CD14 plays a critical role in the establishment of tolerance to LPS. In addition, analysis of the data suggests the existence of a PKC-independent signalling pathway for LPS tolerization and a CD14-independent mechanism for establishing tolerance.

Antigens, CD↗