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Biomedical subjects

R Herrmann

Publications and source records attributed to R Herrmann.

At least 37 records · Page 2Linked to original sources

[Primary non-Hodgkin lymphomas of the central nervous system].

Primary non-Hodgkin's lymphomas (NHL) of the central nervous system are rare brain tumours developing independently of or secondary to disorders of the immune system. In the following review the diagnostic repertoire and various therapeutic modalities are discussed. According to data reported in the literature the therapeutic approach of choice is cranial irradiation with 50 Gy. A positive effect may be expected from additional chemotherapy.

Brain Neoplasms

Pharmacokinetics of 5-fluorouracil after short systemic infusion: plasma level at the end of the distribution phase as an indicator of the total area under the plasma concentration-time curve.

The correlation between single plasma concentration (CP) values of 5-fluorouracil (FU) after a 10-minute i.v. infusion and the total area under the plasma concentration-time curve (AUC) has been studied in 26 cancer patients. FU dose was either 320-550 mg/m2 (seven patients, 13 treatments) or 610-960 mg/m2 (19 patients, 30 treatments). Linear single CP-AUC relationships were found in both dose groups with the CPs at 1, 5, 10, 15, and 30 minutes after the end of infusion. Parameters of linear regression of AUC on single CP differed between the two dose groups. For the high-dose group, the single CPs at repeated treatments were tested as estimators of the total AUC at these treatments, using calibration lines relating total AUC to single CP, which were derived from the data of the first (or only) treatments of all patients. The "best" AUC estimators of the total AUC were the CPs at 10 and 15 minutes after the end of infusion, with a bias of only 2% and an imprecision of only 11% of the AUC values directly determined from the complete concentration-time profiles of the repeated treatments. Because of the close correlation between these single CPs and the total AUC, these CPs should be considered equivalent to the AUC as an overall index of individual FU kinetics after brief infusion of high doses.

Adult

Interaction between light harvesting chlorophyll-a/b protein (LHCII) kinase and cytochrome b6/f complex. In vitro control of kinase activity.

We have previously reported that the cytochrome b6/f complex may be involved in the redox activation of light harvesting chlorophyll-a/b protein complex of photosystem II (LHCII) kinase in higher plants (Gal, A., Shahak, Y., Schuster, G., and Ohad, I. (1987) FEBS Lett. 221, 205-210). The aim of this work was to establish whether a relation between the cytochrome b6/f and LHCII kinase activation can be demonstrated in vitro. Preparations enriched in cytochrome b6/f obtained from spinach thylakoids by detergent extraction and precipitation with ammonium sulfate followed by different procedures of purification, contained various amounts of LHCII kinase activity. Analysis of the cytochrome b6/f content and kinase activity of fractions obtained by histone-Sepharose and immunoaffinity columns, immunoprecipitation and sucrose density centrifugation, indicate functional association of kinase and cytochrome b6/f. Phosphorylation of LHCII by fractions containing both cytochrome b6/f and kinase was enhanced by addition of plastoquinol-1. LHCII phosphorylation and kinase activation could be obtained in fractions prepared by use of beta-D-octyl glucoside but not when 3-[(cholamidopropyl)dimethyl-ammonio]-1-propanesulfonate was used as the solubilizing detergent. Kinase activity could be inhibited by halogenated quinone analogues (2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone and 2,3-diiodo-5-t-butyl-p-benzoquinone) known to inhibit cytochrome b6/f activity. However, kinase activity was inhibited by these analogues in all preparations including those which could not phosphorylate LHCII. We thus propose that the redox activation of LHCII phosphorylation is mediated by kinase interaction with cytochrome b6/f while the deactivation may be related to a distinct quinone binding site of the enzyme molecule.

Ammonium Sulfate

Analysis of three different repeated DNA elements present in the P1 operon of Mycoplasma pneumoniae: size, number and distribution on the genome.

Mycoplasma pneumoniae, a bacterium pathogenic for humans, has a relatively small genome size of 840 kbp. Even though, several repeated DNA elements have been identified in the genome of this prokaryote, particularly within the P1 gene which codes for a major adhesin protein of M. pneumoniae. These elements were characterized in detail with respect to size, number and distribution on the genome, represented by an ordered cloned library covering the complete chromosome. Three different repetitive elements were detected in and around the P1 gene designated as RepMP2/3, RepMP4 and RepMP5. The length of these elements varies between 1.1-1.5 kbp (RepMP4), 1.8 kbp (RepMP2/3) and 1.9-2.2 kpb (RepMP5). They occur at least 8 to 10 times on the chromosome. Possible functions are discussed and a uniform nomenclature for these repeats is proposed.

Blotting, Southern

[Current status of chemotherapy for colonic, rectal and anal carcinoma].

Despite great efforts chemotherapeutic results of metastatic colorectal cancer are still unsatisfactory. In general, single agent treatment with 5-fluorouracil is the standard. The combination of 5-fluorouracil and folinic acid, however, shows favorable preliminary results which can be expected to lead to a small progress in this area. During the last several years the treatment strategy of squamous cell cancer of the anus has changed profoundly. In most patients radical surgery with colostomy has become unnecessary. With combined simultaneous chemotherapy and radiotherapy about 80% of all patients can achieve long term disease free survival.

Algorithms

A scorpion venom neurotoxin paralytic to insects that affects sodium current inactivation: purification, primary structure, and mode of action.

A new toxin, Lqh alpha IT, which caused a unique mode of paralysis of blowfly larvae, was purified from the venom of the scorpion Leiurus quinquestriatus hebraeus, and its structural and pharmacological properties were compared to those of three other groups of neurotoxins found in Buthinae scorpion venoms. Like the excitatory and depressant insect-selective neurotoxins, Lqh alpha IT was highly toxic to insects, but it differed from these toxins in two important characteristics: (a) Lqh alpha IT lacked strict selectivity for insects; it was highly toxic to crustaceans and had a measurable but low toxicity to mice. (b) It did not displace an excitatory insect toxin, 125I-AaIT, from its binding sites in the insect neuronal membrane; this indicates that the binding sites for Lqh alpha IT are different from those shared by the excitatory and depressant toxins. However, in its primary structure and its effect on excitable tissues, Lqh alpha IT strongly resembled the well-characterized alpha scorpion toxins, which affect mammals. The amino acid sequence was identical with alpha toxin sequences in 55%-75% of positions. This degree of similarity is comparable to that seen among the alpha toxins themselves. Voltage- and current-clamp studies showed that Lqh alpha IT caused an extreme prolongation of the action potential in both cockroach giant axon and rat skeletal muscle preparations as a result of the slowing and incomplete inactivation of the sodium currents. These observations indicate that Lqh alpha IT is an alpha toxin which acts on insect sodium channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Some problems in the structural elucidation of fungal metabolites.

In the structural elucidation of natural products, problems may arise owing to extensive signal overlap and line broadening in the NMR spectra as well as unexpected chemical reactions. This is illustrated in the analysis of some novel compounds isolated from fruit bodies of toadstools and slime moulds, including infractopicrin, lascivol, retipolide A, arcyroxepin A and rubroflavin. In some cases, the problems could be solved by spectroscopic techniques such as two-dimensional INADEQUATE experiments, nuclear Overhauser enhancement measurements or X-ray structural analysis; in other cases, chemical transformations were necessary to resolve the structure.

Anti-Bacterial Agents

Prognostic significance of glucocorticoid receptor determination in patients with chronic lymphocytic leukemia and immunocytoma--lack of a positive correlation between receptor levels and clinical responsiveness.

Glucocorticoid receptors (GR) have been suggested to have prognostic significance in patients with CLL treated with chemotherapy containing glucocorticoid. In this study, the GR levels in 65 patients with advanced CLL and immunocytoma (clinical stages III and IV according to Rai) were determined by means of a whole cell assay. The median GR-level was 1,920 bs/c with a range from 0 to 9591. The patients were subsequently treated according to a prospective, randomized trial with either a combination of chlorambucil and prednisolone, or with prednimustine. No significant difference in receptor levels was found between responders (median = 1940 bs/c; n = 47) and nonresponders (median = 1950 bs/c; n = 14). To assess the influence of receptor content on prognosis we have analyzed the relationship between GR content and survival time and duration of response. There was no significant difference in duration of response and in survival between those patients with high (greater than 1920 bs/c) and those with low GR levels (less than 1920 bs/c) (log-rank test). Our data suggest that determination of GR provides no reliable indicator for clinical response to regimens with glucocorticoid as a component in patients with CLL and immunocytoma.

Adult

Ranitidine-associated recurrent acute pancreatitis.

Ranitidine is a safe, widely prescribed drug for the treatment of peptic ulcer disease and is rarely associated with serious adverse reactions. This report describes a patient who suffered three episodes of acute pancreatitis associated with ranitidine prescribed for duodenal ulcer disease. On each occasion the pancreatitis resolved after withdrawal of ranitidine and recurred upon re-exposure. Underlying biliary and pancreatic disease was excluded. There has been no recurrence of pancreatitis in the five years of follow-up since ranitidine was discontinued.

Acute Disease

Antibiotics from basidiomycetes. XXXVII. New inhibitors of cholesterol biosynthesis from cultures of Xerula melanotricha Dörfelt.

Three new inhibitors of cholesterol biosynthesis have been isolated from cultures of Xerula melanotricha and their structures elucidated by spectroscopic methods. Dihydroxerulin (1) in admixture with xerulin (2) strongly inhibits the incorporation of 14C- acetate into cholesterol in HeLa cells while the incorporation of 14C-mevalonate is not affected. Xerulinic acid (3) shows similar biological activities but a higher cytotoxicity.

Agaricales

[Chemotherapy of skin and soft tissue tumors].

Systemic chemotherapy may be used in locally advanced or metastatic soft tissue sarcoma for palliation. Malignant melanoma shows objective responses in about 20% of patients treated with chemotherapy or with cytokines (IL-2, alpha-IFN). Adjuvant chemotherapy has not proven to be effective in either of these entities. The risk of local recurrences in limbs however can be reduced by hyperthermic perfusion with cytotoxic agents. Neoadjuvant (preoperative) treatment of locally advanced tumors needs to be prospectively evaluated. Symptomatic Kaposi sarcoma can be effectively treated with alpha-IFN or chemotherapy.

Antineoplastic Agents