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Biomedical subjects

M Buck

Publications and source records attributed to M Buck.

At least 163 records · Page 9Linked to original sources
PubMed1985

Blood and tissue concentrations of Bisantrene measured by a simple fluorometric assay.

We have developed a simple sensitive fluorometric assay for the measurement of total Bisantrene in plasma, red blood cells, and tissues to facilitate preclinical and clinical pharmacologic assessment of this active anticancer agent. The assay was used to measure the plasma disappearance and tissue concentrations of Bisantrene in the rabbit. Results are comparable to those reported with HPLC assays and with measurement of radioactivity in combusted tissue following IV administration of radiolabeled Bisantrene. We demonstrated that when a plasma concentration of approximately 50 micrograms/ml is not exceeded, Bisantrene remains in solution at that concentration. If Bisantrene is introduced into plasma at a concentration exceeding 50 micrograms/ml, precipitation of the drug is initiated and continues until the plasma concentration is no greater than 15 micrograms/ml. This finding supports our previous recommendation that in clinical trials Bisantrene should be administered at low concentrations over prolonged periods of time to maximize the bioavailability of the drug by minimizing precipitation of the drug in plasma.

Animals↗
PubMed1985

Regional targeting of bisantrene by directed intravascular precipitation.

Targeting of anticancer drugs to specific organs by directed intravascular precipitation was studied in calves using 9-10 anthracenedicarboxyaldehyde bis [(4,5-dihydro-lH-imidazol-2-yl) hydrazone] dihydrochloride (Bisantrene), a clinically active anticancer drug with limited solubility at physiological pH. Rapid injection of Bisantrene in solution at pH 4.5 into the internal iliac artery resulted in concentrations of drug in the urinary bladder wall supplied by the artery that were more than 1000 times those in the same tissue following injection of the same dose of drug IV, the route of administration used clinically. Localization of the orange fluorescent drug to the ipsilateral bladder wall was easily seen. Fluorescence microscopy revealed deposits of drug along the walls of the arteriolar and capillary bed supplied by the artery into which it had been injected. Concentrations of drug in the systemic circulation and in tissues not supplied by the internal iliac artery used for drug injection were lower after intraarterial (IA) drug administration than after IV administration. Pathological studies of the tissues of calves sacrificed at intervals up to four weeks following rapid injection into the internal iliac artery of the same doses of Bisantrene used IV in cancer patients did not reveal evidence of extensive cytotoxicity to the infused organs.

Animals↗
PubMed1985

Low dose cytarabine in acute non-lymphoblastic leukemia or myelodysplastic syndrome: report of six cases and review of the literature.

Low dose cytarabine (10 mg m-2, 12 hourly by subcutaneous injection) was used to treat four patients with acute non-lymphoblastic leukemia, two of whom had failed standard induction chemotherapy, and two patients with refractory anemia with excess blasts in transformation. Following treatment two patients entered complete remission (CR) and two patients had survivals of ten and 18 months in stable partial remission. All patients have died, four of progressive or recurrent leukemia, one of a treatment-related intracerebral hemorrhage, and one of lung carcinoma while in CR. Our experience, and a review of the literature, suggest that in general low dose cytarabine is well tolerated, although myelosuppression is common and thrombocytopenia can be a major problem. This form of treatment appears to offer a useful alternative to intensive induction chemotherapy in those patients in whom such treatment is usually poorly tolerated, and has the advantage of being able to be given to an outpatient.

Acute Disease↗
PubMed1985

Rapidly progressive fatal pulmonary infiltration by lymphoma.

Two patients with diffuse lymphoma, one diffuse large cell and the other diffuse mixed, large and small cell, developed an illness characterised by a high swingeing fever and a pulmonary infiltrate. In both patients there was clinical evidence of chemotherapy-induced tumour response elsewhere at the time lung infiltrates progressed. Blood and sputum cultures, bronchial washings, and, in one case, trans-bronchial lung biopsy did not establish a diagnosis and there was progressive clinical deterioration. Post mortem examination showed widespread involvement of both lungs with lymphoma. The differential diagnosis of fever and pulmonary infiltrates in patients with diffuse lymphoma is discussed, in particular the possibility of this being due to rapidly progressive lymphoma.

Adult↗
PubMed1984

Staphylococcus hominis septicaemia in patients with cancer.

We report two cases of Staphylococcus hominis septicaemia associated with the use of intravenous catheters. Both patients had advanced malignant disease, but infection was eliminated rapidly with antibiotic treatment administered via the catheters. This report confirms the pathogenicity of Staph. hominis, particularly in immunocompromised patients. We recommend the wider use of an effective scheme for the correct identification of blood culture isolates of coagulase-negative staphylococci.

Adult↗
PubMed1984

A modified nucleotide in tRNA as a possible regulator of aerobiosis: synthesis of cis-2-methyl-thioribosylzeatin in the tRNA of Salmonella.

The state of modification of the adenosine residue (A37), found adjacent to the anticodon in tRNAs that recognize codons beginning with U, varies in Salmonella bacteria grown under different physiological conditions. In aerobically grown bacteria, these tRNAs contain ms2io6A and in bacteria grown anaerobically they contain its precursor, ms2i6A. The hydroxylation of the isopentenyl (i6-) side chain of ms2i6A does not occur in the absence of oxygen. When the bacteria are grown under iron or cysteine limitation the tRNAs contain predominantly i6A, rather than ms2i6A, ms2io6A, or io6A. The bacteria do not methylthiolate (ms2-) the i6A under these conditions. A Salmonella miaA mutant lacking the isopentenylation enzyme contains an A37 rather than any of the modified forms. Some of the biosynthetic pathways of the amino acids corresponding to ms2i6A containing tRNAs (phe, tyr, trp, ser, leu, cys) are known to have altered regulation depending on the state of modification of nucleoside A37. This regulation appears to be effected through attenuation. We hypothesize that these varying states of modification are related to electron-acceptor pathways in anaerobic or aerobic growth. The role of ms2io6-adenine (the cytokinin hormone in plants) and i6-adenine (an activator of the cell cycle in animal cells) is discussed as related to the role of modifying enzymes in regulation.

Adenosine↗
PubMed1984

Effect of no treatment, cimetidine 1 g/day, cimetidine 2 g/day and cimetidine combined with atropine on nocturnal gastric secretion in cimetidine non-responders.

We have studied nocturnal acid secretion in patients with duodenal ulcer who met predetermined criteria of poor clinical response to cimetidine. Different groups of patients were investigated receiving either no treatment, cimetidine 1 g/day, cimetidine 2 g/day or cimetidine 1 g/day combined with atropine 4.8 mg/day. The results were compared with those obtained from other patients with duodenal ulcer who were studied in our department but who were not classified as according to their clinical response to cimetidine. The results show that despite adequate absorption, cimetidine has a decreased effect at controlling acid secretion in the poor responders and that increasing the dose of drug does not improve response. Control of acid output was, however, dramatically improved when cimetidine was combined with atropine which suggests that patients who do not respond to H2-receptor blockade should be treated by a combination of cimetidine with an anticholinergic agent.

Atropine↗
PubMed1983

Sequence specificity of tRNA-modifying enzymes. An analysis of 258 tRNA sequences.

The specificity and recognition of tRNA-modifying enzymes may be accounted for in part by nucleotide sequences which are localized next to the modifiable nucleoside. In order to determine the sequence specificity of tRNA-modifying enzymes, we have surveyed 55 published tRNA sequences from Escherichia coli, Salmonella typhimurium and T4 phage. For each modified nucleoside, the nucleotide sequence surrounding the modification site was determined for all tRNAs known to contain the modified nucleoside. Subsequently all tRNAs not containing the modified nucleoside were examined for the absence of the putative recognition site. We present the detailed analysis of 12 modified nucleosides for which we found a strong correlation between the modified nucleoside and the local nucleotide sequence. This suggests that these sequences may be recognition sites for tRNA-modifying enzymes. For each of the 12 modified nucleosides we have identified a recognition sequence present in the tRNA set containing the modification and not in the set without it. All 203 other published tRNA sequences were then examined to see if the sequence specificity rules apply to other organisms, including both prokaryotes and eukaryotes. In several cases a good adherence was found, indicating conservation of the putative recognition sequences.

Animals↗
PubMed1983

Complete analysis of tRNA-modified nucleosides by high-performance liquid chromatography: the 29 modified nucleosides of Salmonella typhimurium and Escherichia coli tRNA.

A high-performance liquid chromatography (HPLC) method has been developed to quantify the major and modified nucleoside composition of total, unfractionated transfer RNA. The method is rapid and sensitive and offers a high degree of chromatographic resolution suitable for quantifying both stable and unstable modified nucleosides. It is nondestructive and allows the recovery of nucleosides for further characterization. We apply the method in the analysis of the 29 modified nucleosides in tRNA from Salmonella typhimurium (and Escherichia coli) and show it to be useful in examining changes in the modified nucleoside content of tRNA. Such changes may be important in regulation.

Chemical Phenomena↗
PubMed1983

Cimetidine or vagotomy? Comparison of the effects of proximal gastric vagotomy, cimetidine and placebo on nocturnal intragastric acidity and acid secretion in patients with cimetidine resistant duodenal ulcer.

Nocturnal pH, acid output and volume of gastric secretion have been measured in a group of patients who were referred for surgery because of a poor clinical response to cimetidine. Patients were studied after no treatment, cimetidine 1 g/day and proximal gastric vagotomy. Although pH and acid output were controlled better with cimetidine than no treatment this was not true for volume of secretion. Vagotomy was significantly better than cimetidine in controlling pH, acid output and volume of gastric secretion. The results suggest that cimetidine non-responders should have a good result from proximal gastric vagotomy, making more radical forms of gastric surgery unnecessary.

Adult↗
PubMed1983

Exposure to men influences the occurrence of ovulation in women.

It has been demonstrated that exposure to men has the capacity to shorten the menstrual cycle in women. In the present study, the impact of the variables of sleeping arrangements and sexual activity were examined on both menstrual cycle length and the occurrence of ovulation as determined by basal body temperature charts. It was found that women who spent at least two or more nights with men during a forty day period exhibited a significantly higher rate of ovulation (p less than 0.05) than those spending no or one nights. Cycle length was not affected by sleeping arrangements. Furthermore, frequency of sexual intercourse was unrelated to either cycle length or likelihood of ovulation. The mechanism underlying this phenomenon is unknown but it is conjectured that it is pheromonal in nature.

Coitus↗
PubMed1983

The leader mRNA of the histidine attenuator region resembles tRNAHis: possible general regulatory implications.

The leader region of the mRNA of the his operon is involved in regulating the frequency of transcription termination through attenuation and therefore expression of the his structural genes. We now report that the his leader mRNA has a remarkable sequence homology with the tRNAHis molecule. Of the 75 nucleotides forming tRNAHis (not counting the -CCA tail), 45 are homologous to nucleotide sequences found in the his leader mRNA. This homology extends to secondary structures which can form in the leader mRNA. The stems and loops of tRNAHis are thus related to those of the his leader mRNA which play a critical role in regulating expression of the his operon through attenuation. Many proteins that bind tRNAHis thus might bind to the similar structures found in the his leader mRNA and influence regulation by favoring the attenuator or anti-attenuator configuration. These include tRNA-modifying enzymes, the histidyl-tRNA synthetase, and the hisG enzyme. The significance of similar structures in other regulatory systems is discussed, particularly in relation to the role of tRNA-modifying enzymes as important regulatory molecules in both prokaryotes and eukaryotes.

Base Sequence↗
PubMed1983

Single nocturnal dose of an H2 receptor antagonist for the treatment of duodenal ulcer.

Twenty four hour intragastric acidity and nocturnal acid output have been measured over five separate 24 hour periods in each of 12 patients with duodenal ulcer receiving either placebo, cimetidine 400 mg bd, cimetidine 300 mg nocte, ranitidine 150 mg bd, or ranitidine 300 mg nocte. In these doses ranitidine was significantly more effective at decreasing intragastric acidity and nocturnal acid output than cimetidine. There was no significant difference between twice daily ranitidine and night time ranitidine or between twice daily cimetidine and night time cimetidine in the reduction of intragastric acidity. Nocturnal acid output was controlled significantly better with ranitidine at night, twice daily dosage of ranitidine, and cimetidine at night, than by the twice daily dosage of cimetidine. It is suggested that a single nocturnal dose of cimetidine or ranitidine should be evaluated in a clinical trial.

Cimetidine↗
PubMed1982

cis 2-Methylthio-ribosylzeatin (ms2io6A) is present in the transfer RNA of Salmonella typhimurium, but not Escherichia coli.

We have identified the cis isomer of N6-(4-hydroxy-isopentenyl)-2-methylthioadenosine (ms2io6A) as a component of the tRNA of Salmonella typhimurium. This is the first report of this compound in the tRNA of any member of the enterobacteriaceae: the nucleoside was previously thought to be found exclusively in plants or plant associated bacteria. Interestingly, all E. coli strains examined were found to lack ms2io6A. Evidence is presented which suggests S. typhimurium tRNA also contains low levels of 5-carboxymethylaminomethyl-2-thiouridine (cmnm5s2U) in addition to 5-methylaminomethyl-2-thiouridine (mnm5s2U).

Adenosine↗
PubMed1982

Lysine tRNAs from Bacillus subtilis 168: structural analysis.

The primary sequence was established for two lysine tRNA isoacceptors which differ in abundance during development in Bacillus subtilis. Both tRNAs shared the same primary sequence but differed in the degree of post-transcriptional modification in the anticodon loop. The earlier eluting species, tRNA lys 1, had an unmodified C in position 32 and a mixture of N-[9-beta-ribofuranosyl) purin-6-ylcarbamoyl]-L-threonine, t6A, and N-[(9-beta-D-ribofuranosyl-2-methylthio-purin-6-yl)carbamoyl]threonine, ms2t6A, in position 37. The later eluting species, tRNA Lys 3, which is the more efficient in protein synthesis, had a modified C in position 32 and only ms2t6A in position 37. The possibility exists that modification to make a more efficient tRNA species may be part of a functional interaction between the translational and transcriptional changes that are part of the differentiation process in B. subtilis.

Anticodon↗
PubMed1982

Iron mediated methylthiolation of tRNA as a regulator of operon expression in Escherichia coli.

E. coli growing in the presence of iron-binding proteins produced tRNAtrp and tRNAphe molecules containing i6A instead of ms2i6A adjacent to the anticodon. These undermodified tRNAs functioned less efficiently than the fully modified molecules when translating synthetic polynucleotides containing contiguous codons in an in vitro system, but did not limit the translation of MS2 RNA. We examined the possibility that the altered tRNAs with lowered translational efficiencies could relieve transcription termination at the trp and phe attenuators and lead to increased operon expression under iron restricted conditions. Using trpR mutants we found that there was indeed greater expression of the trp operon during iron restricted growth. This increase was attributable solely to the tRNA alteration induced by iron restriction.

Conalbumin↗