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Biomedical subjects

R Herrmann

Publications and source records attributed to R Herrmann.

At least 55 records · Page 3Linked to original sources

Cloning of the complete Mycoplasma pneumoniae genome.

The complete genome of Mycoplasma pneumoniae was cloned in an ordered library consisting of 34 overlapping or adjacent cosmids, one plasmid and two lambda phages. The genome size was determined by adding up the sizes of either the individual unique EcoRI restriction fragments of the gene bank or of the XhoI fragments of genomic M. pneumoniae DNA. The values from these calculations, 835 and 849 kbp, are in good agreement. An XhoI restriction map was constructed by identifying adjacent DNA fragments by probing with selected cosmid clones.

Cloning, Molecular

Allergic reaction with immune hemolytic anemia resulting from chlorambucil.

In a 73-year-old female with chronic lymphocytic leukemia we observed an acute illness with shivering, high fever, and hemolytic anemia following chlorambucil administration. Reexposure in a controlled clinical situation suggested an allergic drug reaction. In an in vitro assay, we were able to demonstrate chlorambucil as the causative agent of immune hemolysis.

Aged

Intrahepatic 5-FU retreatment of liver metastases of colorectal cancer that were progressive under previous systemic chemotherapy.

Sixteen patients with liver metastases of colorectal cancer that were progressive under systemic chemotherapy were treated by hepatic arterial infusion therapy. 5-fluorouracil (5-FU) with a daily dosage of 1 g/m2/day was given continuously for 5 consecutive days at 3-week intervals. Restaging after three cycles of treatment revealed three partial remissions (PRs) and five patients with stable disease (SD). Duration of response was a median 17 months in patients with PRs. Survival time of the total group of patients was 11.6 months. Patients with PRs had 19 months, patients with SD 13 months, and patients with progressive disease 9 months median survival time. In 12 of the patients, tumor growth was limited to the liver for a long period of time, and extrahepatic metastases occurred in the end-stage disease. Therefore, in patients with progressive liver metastases of colorectal cancer under systemic chemotherapy and with no extrahepatic metastases, intrahepatic arterial chemotherapy may offer a further chance for tumor control.

Adenocarcinoma

Hepatic involvement in listeriosis.

We report an adult with listeriosis. Sequential liver biopsies demonstrated the resolution of associated granulomas and microabscesses after the administration of high doses of penicillin for ten days. This observation has not previously been reported.

Aged

[Proof of bioequivalence of two nifedipine preparations].

A crossover-study was performed with 20 volunteers in order to demonstrate the bioequivalence of two nifedipine preparations after single dose application. Methods for demonstrating bioequivalence were according to the APV (Arbeitsgemeinschaft für pharmazeutische Verfahrenstechnik)- and FDA-guidelines; in addition some new but less well-known biometric procedures were used. Bioequivalence could be proved for the criteria AUC, Cmax and tmax as stated in the nifedipine monograph of Zentrallaboratorium Deutscher Apotheker.

Adult

Physical mapping of the Mycoplasma pneumoniae genome.

In order to study the genome organization of Mycoplasma pneumoniae a cosmid library of M. pneumoniae DNA was established using a newly designed cosmid vector (pcosRW2). From this library 32 overlapping clones were isolated covering a contiguous 720 kbp DNA segment representing about 90% of the genome assuming a genome size of about 800 kbp.

Base Sequence

Repetitive DNA sequences in Mycoplasma pneumoniae.

Two types of different repetitive DNA sequences called RepMP1 and RepMP2 were identified in the genome of Mycoplasma pneumoniae. The number of these repeated elements, their nucleotide sequence and their localization on a physical map of the M. pneumoniae genome were determined. The results show that RepMP1 appears at least 10 times and RepMP2 at least 8 times in the genome. The repeated elements are dispersed on the chromosome and, in three cases, linked to each other by a homologous DNA sequence of 400 bp. The elements themselves are 300 bp (for RepMP1) and 150 bp (for RepMP2) long showing a high degree of homology. One copy of RepMP2 is a translated part of the gene for the major cytadhesin protein P1 which is responsible for the adsorption of M. pneumoniae to its host cell.

Base Sequence

Metabolites of 5-fluorouracil in plasma and urine, as monitored by 19F nuclear magnetic resonance spectroscopy, for patients receiving chemotherapy with or without methotrexate pretreatment.

19F NMR spectroscopy at 470 MHz (11.7 Tesla) has been used to directly measure the levels of 5-fluorouracil (FU) and its fluorine-containing catabolites in plasma and urine of colon cancer patients after i.v. infusion (10 min) of 60-230 mumol (8-30 mg) FU/kg, either with or without pretreatment with methotrexate (5.1-12.5 mg/kg). With a 1.5-ml sample the minimum metabolite concentration that can be quantified is approximately 15 +/- 5 microM within 30 min and 3 +/- 1 microM within 12 h of data acquisition. The first and second catabolites of FU, dihydrofluorouracil and alpha-fluoro-beta-ureidopropanoic acid, exhibit steady-state behavior with dose-dependent plasma concentrations of 5-40 microM for approximately 10-90 min after infusion (12 patients, 16 treatments). The final catabolite alpha-fluoro-beta-alanine (FBAL) was detected in plasma after 5-15 min, and the rate at which its concentration increased was independent of FU dose, while the maximum concentration reached at about the time FU disappeared (FU less than 5 microM in 1-2 h) was dose-dependent. The area under the time curve for FU in plasma increased more than linearly with dose. Several patients showed elevated levels of free fluoride anion (F-) in plasma (63 samples: median, 5 microM; maximum, 33 microM). In urine all of the above catabolites and F- could be observed. In samples with pH greater than or equal to 7.3 (methotrexate patients, due to bicarbonate infusion) N-carboxy-FBAL was also found in significant amounts. Urinary excretion of FU and catabolites amounted to 2.6-30% of the dose within 2 h (14 patients, 18 treatments) and 60-66% within 24 h (three patients). The ratio FU/creatinine in 2-h urine increased more than linearly with FU dose. Urinary fluoride concentration reached a maximum during the first day after FU infusion and returned to normal background levels after 2-3 days (four patients). The pattern of FU catabolites observed in plasma or urine did not differ significantly between responders and nonresponders to therapy or between patients with FU monotherapy and patients with methotrexate pretreatment. Cytotoxic FU anabolites, i.e., nucleotides, were not detected in plasma or urine (i.e., are less than 3 microM). Their detection in tumor tissue will be required for an assessment of individual responsiveness to FU. Possible toxic metabolic products derivable from FBAL, e.g., 2-fluoroacetate or 2-fluorocitrate, were not detected (i.e., are less than 3 microM) in plasma or urine.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged

Analysis of transcription and processing signals in the 5' regions of the two Mycoplasma capricolum rRNA operons.

The transcription and RNA processing signals of the rRNA operons (rrnA and rrnB) of Mycoplasma capricolum were analyzed by mapping the 5' ends of in vivo and in vitro synthesized RNAs. The results of both in vitro and in vivo analyses point to the rrnA operon being transcribed from two promoters (P1 and P2) into large precursor RNAs. Transcripts initiating at P1 contain two tRNAs, and probably 16 S, 23 S, and 5 S rRNAs, whereas the transcripts starting from P2 consist only of the three rRNAs. The precursor RNAs are processed via distinct intermediates into mature tRNAs and rRNAs. In vivo experiments indicated that the rrnB operon is transcribed only from one promoter, although a second promoter could be identified using cell free extracts. The rrnB operon does not contain tRNA genes, but the precursor is still processed in the same way as the rrnA precursor that is synthesized from P2.

Base Sequence

Folinic acid effect on 5-fluorouracil kinetics in vivo.

Synergy of folinic acid and FU has been shown in several experimental systems. In the present study we examined the kinetics of concurrent administration of folinic acid on the kinetics of FU in an in vivo model. Folinic acid significantly increased the amount of FU bound to the TS complex. In the sequential combination of MTX and FU folinic acid had no additional effect. The amount of FU incorporated into RNA was not affected in any of the treatment groups. The results indicate that folinic acid may improve FU cytotoxicity by increased FU binding to TS but has no additional effect on the synergistic sequential MTX-FU combination.

Animals

Preoperative chemotherapy in esophageal cancer. A phase II study.

Forty-two patients with localized squamous cell carcinoma of the esophagus were treated according to a phase II study with cisplatin, vindesine and bleomycin (modified Kelsen schedule) prior to surgery. In 17 of these patients partial remission was achieved and in two cases complete remission. Of the 40 patients who were candidates for surgery, 4 were inoperable. In 22 cases the tumor was removed in a potentially curative manner and in 14 patients a palliative resection was performed. There were 4 post-operative deaths among 36 resected patients. Anastomic leakage occurred in 5 and severe cardiopulmonary complications in 4 patients. The side effects of the preoperative treatment were acceptable. A high resectability rate and a comparatively high survival rate in patients who responded to chemotherapy suggest that the preoperative treatment employed might be of value.

Antineoplastic Combined Chemotherapy Protocols