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Biomedical subjects

H Lindner

Publications and source records attributed to H Lindner.

At least 91 records · Page 5Linked to original sources

Primary adjuvant whole abdominal irradiation in ovarian carcinoma.

Eighty-four patients with an ovarian carcinoma Stage I-III received an adjuvant whole abdominal irradiation (WAI) with pelvic boost postoperatively. Surgery included a bilateral salpingo-oophorectomy, hysterectomy, and omentectomy in 59% of the patients; in 41% surgery was less radical. For the whole abdominal irradiation we used the moving-strip method on 43 patients. The open-field technique was used on the other patients. Median dose of WAI was 22.5 Gy and median pelvic dose was 45.5 Gy. After a median follow-up of 68.5 months, a 5-year survival rate of 64 +/- 5.7% was determined, as well as a 5-year NED rate of 61.2 +/- 5.7%. Five-year survival rate was 80.1 +/- 7.4% in Stage I, 64.1 +/- 9.7% in Stage II, and 35.4 +/- 11.6% in Stage III. Five-year survival depended on tumor rest significantly. There was a trend to better prognosis when surgery was complete and grade was G1 or G2. The risk factor according to Dembo proved to be the most reliable prognostic factor: the 5-year survival rates were 75.0 +/- 6.3% for patients with intermediate risk and 20.1 +/- 10.4% for those with high risk (p = 0.001). Side effects were generally well tolerated. We only saw one serious complication, a radiation-induced small bowel obstruction.

Abdomen↗

[Postoperative adjuvant whole abdomen irradiation in ovarian cancer].

Seventy-nine patients with ovarian carcinoma stage I-III postoperatively received a whole abdominal irradiation (median dose: 22.5 Gy) followed by pelvic boost irradiation (median pelvic dose: 45 Gy) as the sole adjuvant therapy. Surgery preceding the irradiation was radical only in 59 percent of the patients. Whole abdominal irradiation was performed either in the moving-strip-technique or the open-field-technique. The median follow-up time was 57 months. The overall and the progression-free five-year survival rate of the whole group is 66 +/- 6% and 63 +/- 6%, respectively. We have not seen a clear-cut dependence of the survival rates on the completeness of the surgery, on tumor histology or grading. In a statistically significant way, the survival rates depend on the stage, the presence of tumor rests, and, above all, on the risk group. The overall five-year survival rate for the intermediate-risk patients is 78 +/- 7% and 22 +/- 11% for high risk patients. There aren't any randomized studies concerning the optimal adjuvant therapy for intermediate-risk patients. Because of the reproduceable results and the infrequent toxicity, whole abdominal irradiation seems to be a treatment equivalent to other adjuvant therapies for these patients.

Adult↗

Identification of ADP-ribosylated histones by the combined use of high-performance liquid chromatography and electrophoresis.

Reversed-phase high-performance liquid chromatography (HPLC) was employed for analysing mono- and oligo(ADP-ribosyl)ated histones. Under the chromatographic conditions described, the ADP-ribosylated histones showed similar retention times to the unmodified histones, although the molecular weight and the charge of the proteins are significantly altered by their modification. The simultaneous elution of unmodified and labelled modified histones was detected by two types of gel electrophoresis and by autoradiography. In addition, the HPLC fractions did not display overlapping ladders of the multiply modified histones, as is commonly seen in one-dimensional electrophoretic analyses of unfractionated material. Hence individual bands could be unambiguously assigned. After in vitro labelling of isolated rat liver nuclei, the following ADP-ribosylated and unmodified histones were identified by HPLC and gel electrophoresis: histone H1(0), four histone H1 subfractions, histone H2A.1, histone H2A.2, oxidized histone H2A.2, histone H2A.X, histone H2A.Z, histone H2B, three histone H3 variants and histone H4.

Adenosine Diphosphate Ribose↗

[Treatment of otherwise incurable tumor diseases in childhood using whole-body hyperthermia and chemotherapy].

Conventional methods of treatment having failed in 17 children (aged 9/12 to 16 5/12 years) with incurable solid malignant tumours underwent whole-body hyperthermia (41.8-42.0 degrees C, for 2-3 h), hyperglycaemia (20-25 mmol/l) and polychemotherapy. Five children had neuroblastoma (stage 4), three Wilm's tumour (stage 4 or 5, unfavourable histology), five skeletal sarcoma with metastases, three inoperable malignant liver tumour, and one brainstem tumour of unknown histology. Whole-body hyperthermia was induced by extracorporeal blood warming in an haemodialysis apparatus under neuroleptic analgesia, thermistors measuring the temperature in the oesophagus, rectum, trachea and skin. There were on average four treatment sessions (between one and ten, total 58), a week apart. The result could be assessed in 12 children: one persisting complete remission (19 months-metastasising renal rhabdoid tumour), eight partial or incomplete remissions, and three nonresponders (osteogenic sarcoma; Ewing sarcoma; brainstem tumour). If the risk can be satisfactorily judged the method is useful and of bearable toxicity. The results point to a high antitumour effectiveness of combined hyperthermia and chemotherapy.

Adolescent↗

Separation of Friend erythroleukaemic cell histones and high-mobility-group proteins by reversed-phase high-performance liquid chromatography.

A procedure for the rapid separation of histones and high-mobility-group (HMG) proteins from Friend erythroleukaemic cells (line F4N) by reversed-phase high-performance liquid chromatography is reported. By using a Nucleosil 300-5 C4 column and a multistep water-acetonitrile gradient containing 0.1% trifluoroacetic acid, the HMG-1 and HMG-2 proteins, several H1 subfractions including H1(0), H4, H2B, two H2A variants and two H3 subfractions were separated. Under changed conditions, by applying a varied acetonitrile gradient system, even two H2B variants were fractionated. The methods described seem to be a real alternative to the time-consuming polyacrylamide gel electrophoresis.

Cell Line↗

A new h.p.l.c. isolation procedure for chicken and goose erythrocyte histones.

Total chicken erythrocyte histones were separated by reversed-phase h.p.l.c. using a multi-step acetonitrile gradient in a very short time (35 min). The proteins were eluted in the following order: H1, H5, H2B, H2A.2, H4, H2A.1 and H3.2. Applying a special gradient system adapted for the separation of very-lysine-rich histones, chicken erythrocyte H5 was resolved into two subfractions. Their electrophoretic mobilities were identical in both SDS and acetic acid/urea/Triton polyacrylamide-gel electrophoresis, but different in free-flow electrophoresis. Amino-acid-sequence analyses revealed that the two components only differ with respect to position 15, one having glutamine in that position and the other arginine. A separation of histones prepared from goose erythrocytes disclosed no H5 subfractionation. Furthermore, histones obtained from anaemic-chicken blood were analysed by the above-mentioned h.p.l.c. conditions. An alteration in the relation of H1 to H5 was detected, but no further differences in the number and quantity of the histones and histone variants were observed as compared with the corresponding proteins processed from normal-chicken blood.

Anemia↗

[Simultaneous occurrence of Wilm's tumor and multiple lung hamartomas in a 15-year-old girl].

The observation of multiple adenofibroleiomyomatous hamartomas of the lung in a 15-year-old girl 7 years after treatment of a Wilms' tumour caused diagnostic difficulties that are discussed. The diagnosis was finally established by thoracotomy and tumour resection. The simultaneous occurrence of Wilms' tumours and benign or malignant tumours points to genetic factors in the development of both tumours.

Adolescent↗

Histone separation by high-performance liquid chromatography on C4 reverse-phase columns.

Previous work in our laboratory (Lindner, H., Helliger, W., and Puschendorf, B. (1986) J. Chromatogr. 357, 301-310) described a rapid separation of H1 and core histones by reverse-phase high-performance liquid chromatography using a Bio-Rad Hi-Pore butyl (C4) silica-based column. Despite the short elution time, a high resolution of the different histone fractions, except H4 and H2A (MHP), could be obtained. In this report we present a method for the separation of H4 and H2A (MHP) as well, while maintaining a similar analysis time. By varying the gradient, trifluoroacetic acid concentration (0.05%), and flow rate (1.3 ml/min) the histones were eluted from the C4 column in the following order: H1 (MHP), H1 (LHP), H2B, H2A (LHP), H4, H2A (MHP), H3 (LHP), and H3 (MHP). LHP and MHP refer to less and more hydrophobic histone variants. The identification of the individual protein fractions was performed by comparison the retention times with pure histone markers as well as by gel electrophoresis.

Animals↗

[Tumor biochemistry as basis for advances in tumor chemotherapy].

Oncogenes, onc-gene products and the concept of autonomous self-stimulation of tumor growth by autocrine production of growth factors are discussed with regard to the development of new antitumor agents. The significance of the plasma membrane as an attractive target in tumor chemotherapy is emphasized. Membrane bound enzymes and related reactions which are involved in growth factor dependent regulation of cell proliferation offer new targets for antitumor chemotherapy. Examples demonstrating the antiproliferative effects of phospholipase-C and calmodulin inhibitors are presented. A synergistic effect of these drugs with alkylating agents is observed. Studies devoted to the improvement of alkylating antitumor agents have also led to the plasma-membrane as a particularly suited target. The same may be true for other antitumor agents like anthracyclines and platinum complexes for which evidence exists implicating the involvement of cellular membranes in the mechanism of cytotoxic action.

Alkylating Agents↗

Plasma membrane as target of alkylating agents.

N mustard resistant Walker cells exhibit the same frequency of DNA interstrand cross-links and the same rate of cross-link removal as the sensitive parental line. Employing cytostatically active concentrations of chlorambucil covalently bound to polyethyleneimine, the extent of DNA cross-linking is reduced to levels observed in the presence of nontoxic concentrations of free chlorambucil. It is concluded, therefore, that DNA cross-links alone are not sufficient to explain the inhibition of cell multiplication by alkylating agents and that additional mechanisms have to be considered. Evidence for an interference of alkylating agents with several enzymes of the plasma membrane is presented. An inhibition by N mustard of the furosemide-sensitive Na+/K+/Cl- -cotransport and the Na+/H+-antiport is described in greater detail. Considering the fact that the enzymes which are affected by alkylating agents are controlled by growth factors it was investigated whether a synergism between inhibitors of early growth-factor-controlled reactions and alkylating agents is to be seen. It is demonstrated that mepacrine, an inhibitor of phospholipase C, and the calmodulin binding drugs, chlorpromazine and flunarizine, amplify the action of N mustard.

Adenosine Triphosphatases↗