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Biomedical subjects

R C Miller

Publications and source records attributed to R C Miller.

At least 217 records · Page 12Linked to original sources
PubMed1983

Specificity of action of Ca++ entry blockers. A comparison of their actions in rat arteries and in human coronary arteries.

Among the large number of compounds which inhibit the contraction evoked by calcium in depolarized smooth muscle, calcium entry blockers are those that specifically block calcium entry during muscle activation. They affect neither Ca++ efflux nor intracellular Ca++ release. A comparative study of the diphenylpiperazines, cinnarizine and flunarizine, with the dihydropyridine, nifedipine, allows conclusions to be drawn as to their specificity of action. We have also examined the action of calcium entry blockers, considering tissue and stimulus selectivity. The inhibition of smooth muscle contraction can be quantitatively related to blockade of Ca++ influx. In rat aorta and mesenteric arteries, the potency of Ca++ entry blockers depends on the stimulus in the following order of sensitivity: K depolarization greater norepinephrine greater than PGF2 alpha. As far as flunarizine, but not nifedipine, is concerned, the activity is higher in mesenteric arteries than in aorta. This raises the possibility that calcium channels have receptor and organ specificity, a hypothesis which is supported by the observation that the order of potency of several calcium entry blockers is different in various vessels including human coronary arteries, and that the action of the blockers increases with the age of the patient.

Adult↗
PubMed1983

[Two cases of large functioning parathyroid adenoma in atomic bomb survivors].

In a study by the Radiation Effects Research Foundation, Hiroshima and Nagasaki, of parathyroid tumors in autopsy cases, 18 cases of parathyroid adenoma were detected among 6, 102 cases that were autopsied between 1961-77. Two of these were giant adenomas 5 cm in diameter, complicated with hyperthyroidism. Both were atomic bomb survivors of Hiroshima. One was exposed to 55 rad at the age of 51 and died at age 71. The other was exposed to 28 rad at age 44 and died at age 71. These two cases are reported with a review of the literature on parathyroid tumors that developed following irradiation of the head and neck.

Adenoma↗
PubMed1982

Transcription of cloned transfer RNA genes from Drosophila melanogaster in a homologous cell-free extract.

Cloned Drosophila melanogaster tRNA genes have been transcribed in a homologous cell-free extract isolated from a Schneider II cell line. The major product of the reaction is a tRNA precursor which is processed to a tRNA sized species. The kinetics of transcription has been followed for 5 different valine tRNA gene clones. The results demonstrate formation of stable transcription complex with at least two kinetic steps. While the rate of formation of the transcription complex is similar to different clones, the ultimate rate of transcription varies dramatically. Comparison of the DNA sequence of the tRNA genes suggests that rate determining nucleotides lie outside the canonical tRNA split-internal promoters.

Animals↗
PubMed1982

Genes for tRNALys5 from Drosophila melanogaster.

The sequences of two cloned genes from Drosophila which hybridize with tRNALys5 are reported. One gene, in plasmid pDt39, has a sequence which corresponds to the sequence of tRNA. The other gene, in pDt59R, differs in three nucleotides pairs. Both plasmids are transcribed in vitro with extracts of Drosophila Kc cells to give full-sized tRNA precursors with four additional nucleotides at the 5'-end as well as truncated molecules containing 35 nucleotides. This premature termination occurs in a block of four T residues within the mature coding region. Sequences flanking the tRNA genes show little in common except for the blocks of five or more T-residues beyond the 3'-end of the gene. pDt39 hybridizes to 84AB on the polytene chromosomes of Drosophila and pDt59R hybridizes to 29A.

Animals↗
PubMed1982

A comparative study of the localization of wheat-germ agglutinin and its potential receptors in wheat grains.

Wheat-germ agglutinin is located only in the embryo of a dry wheat seed and not in the endosperm tissue. This distribution remains unaltered for up to 96 h of germination and growth. The lectin is found not only in a freely soluble form but also in reversible association with particulate subcellular components. There appear to be no poly-peptides that can be solubilized with sonication and aqueous buffers from the embryo tissue that can interact with the agglutinin. This suggests that in vivo the lectin remains uncomplexed to endogenous glycoconjugates or is only able to bind to glycosylated integral membrane polypeptides. Alternatively the potential endogenous receptor(s) to wheat-germ agglutinin may not contain a polypeptide. Although the lectin is not present in the endosperm, seven polypeptides able to interact in a reversible way with wheat-germ agglutinin could be purified from that tissue.

Chromatography, Affinity↗
PubMed1982

Acute and long-term cytogenetic effects of treatment in childhood cancer: sister-chromatid exchanges and chromosome aberrations.

The incidence of chromosomal aberrations in banded karyotypes and of sister-chromatid exchanges (SCEs) was determined in the lymphocytes of survivors of childhood cancer as 2 parameters which are pertinent in assessing the genetic damage induced by chemotherapy. The proportion of cells with chromosome breakage or structural rearrangement-type aberration was 1 cell in 67 in a control group of 8 untreated cancer patients and 2 parents of cancer patients, 1 cell in 8 in 12 patients currently on therapy, and 1 cell in 50 in 17 patients sampled 6 months to 35 years post-treatment. The range of mean SCE levels per cell was 4.5-6.5 in the untreated cancer patients, 4.0-9.6 in non-cancer controls, 3.3-33.7 in patients on therapy, and 4.6-9.7 in post-therapy survivors. Considerably variability was observed between individuals with both SCE and breakage assays but therapy-induced increases in SCEs were not necessarily correlated with increased levels of aberrations arising from chromosomal breakage.

Adult↗
PubMed1982

The structures of genes hybridizing with tRNA4Val from Drosophila melanogaster.

Segments of cloned Drosophila DNA from four recombinant plasmids that hybridize with tRNA4Val have been sequenced. The segments from pDt92R and pDt120R that hybridize to 90C on the third polytene chromosome appear to be either repeats or alleles. They contain one structural gene each of identical sequence but differ at eight sites in 506 base pairs. The structural genes differ at four sites from the sequence expected from that of tRNA4Val. A third plasmid, pDt14, which hybridizes to 89BC on the third chromosome, also contains a structural gene with the same sequence as those in pDt92R and pDt120R. In addition, pDt14 has a gene for tRNA2Phe 214 base pairs upstream and with the same polarity as the tRNA4Val gene. The tRNA2Phe gene contains a 23-base pair segment identical with the corresponding segment in the tRNA4Val genes except for one base pair. The fourth plasmid investigated, pDt55, hybridizes to 70BC. It contains two tRNA4Val genes 525 base pairs apart with opposite polarity. These genes have identical sequences, which corresponds to that expected from the sequence of tRNA4Val. There is no evidence that the first three tRNA4Val genes are expressed at any stage during the development of Drosophila.

Animals↗
PubMed1982

Clinical hyperthermia: results of a phase I trial employing hyperthermia alone or in combination with external beam or interstitial radiotherapy.

Forty-three patients with advanced, locally accessible neoplasms were treated in a Phase I clinical trial employing hyperthermia alone or hyperthermia combined with either high-dose-rate external beam or low-dose-rate interstitial radiotherapy (interstitial thermoradiography). All patients had failed previous conventional therapeutic attempts, including various combinations of surgery, chemotherapy and radiation therapy. Many had received tolerance or near tolerance levels of prior radiation that restricted dose prescriptions in this trial to subcurative values. A number of tumors with different histologies were treated, including squamous cell carcinoma (14), adenocarcinoma (14), melanoma (8), malignant fibrous histiocytoma (2), and sarcoma (5). The response evaluation criteria used included no response (NR--less than 50% decrease in tumor volume), partial response (PR--50% less than or equal to tumor volume reduction less than 100%) and complete response (CR--complete tumor disappearance). For all tumor types, hyperthermia therapy alone resulted in a total response rate of 45% (27% PR, 18% CR). Hyperthermia combined with high-dose-rate external beam radiotherapy yielded a total response rate of 80% (53% PR, 27% CR). Seventeen patients treated with interstitial thermoradiography displayed a 100% total response rate (29% PR, 71% CR). By tumor histologies for all treatment groups, total response rates have ranged from 50% to 79% for all types except melanoma, which has shown a 100% (8/8) response rate to date. Response durations have varied from one to 24 months. Twelve of the 43 patients remain alive; three have no evidence of disease (NED) while nine have either stable local disease or are NED in the treated volumes but have metastatic disease. Complications have been minimal and have included one third-degree burn and three second-degree burns from fringing RF fields, one vaginal-rectal fistula, a superficial focal soft tissue necrosis, and some minor blistering. The results of this Phase I trial demonstrate that hyperthermia alone or combined with radiation can be safely applied in the treatment of malignant disease. Most importantly, the data suggest that hyperthermia, especially when combined with interstitial thermoradiography, can yield remarkable results in the eradication of local cancers.

Adenocarcinoma↗
PubMed1982

RNA-DNA hybridization analyses of tRNA-Val-3b in Drosophila melanogaster.

Transfer RNA was extracted from 50-300 mg of adult flies and specifically labeled in vitro. The level of individual isoacceptors was quantitated by efficient annealing to Drosophila tRNA genes carried on recombinant DNA plasmids immobilized on nitrocellulose filters. The level of tRNAVal3b in the tRNA isolated from flies deficient in the major tRNAVal3b loci has been examined. The results show that deletion of the major tRNAVal3b loci resulted in a reduction of approximately 50% in the level of tRNAVal3b but did not produce the Minute phenotype; furthermore the effects of deficiencies at two loci were approximately additive.

Animals↗
PubMed1982

Molecular cloning of a Cellulomonas fimi cellulose gene in Escherichia coli.

A sensitive and simple immunoassay was developed to screen Escherichia coli transformed with recombinant DNA plasmids carrying a cellulase gene. The assay was used to identify a recombinant DNA plasmid carrying at least one cellulase gene from Cellulomonas fimi. The enzyme present in extracts of E. coli carrying the plasmid was active in catalysing the hydrolysis of carboxymethylcellulose as indicated by the production of reducing sugars.

Cellulase↗
PubMed1982

Actions of prostaglandin F2 alpha and noradrenaline on calcium exchange and contraction in rat mesenteric arteries and their sensitivity to calcium entry blockers.

1 The actions of prostaglandin F2 alpha (PGF2 alpha) and noradrenaline on contraction and 45Ca exchange have been studied in rat mesenteric arteries. 2 PGF2 alpha and noradrenaline contracted rat isolated mesenteric artery preparations to about the same extent. The PGF2 alpha-stimulated contractions, unlike those produced by noradrenaline, were completely inhibited in calcium-free physiological solution. 3 The calcium entry blocking drugs, cinnarizine and flunarizine, had little effect on the resting exchange of calcium in the arterial smooth muscle, but inhibited PGF2 alpha-stimulated contractions and 45Ca uptake to a similar extent. 4 Flunarizine was about 7 fold more potent as an inhibitor of noradrenaline- than of PGF2 alpha-mediated contraction and 45Ca uptake and this ratio was about 50 for cinnarizine. 5 EGTA (1.25 mM) produced a relaxation of noradrenaline and PGF2 alpha-induced maximal contractions. Measured over the first 2 min of EGTA contact, the rate of relaxation was much faster in noradrenaline than in PGF2 alpha-stimulated preparations. 6 Turnover of cellular calcium (influx plus efflux) during the first 2 min of noradrenaline contact was much greater than that produced by PGF2 alpha, largely due to a greater effect of noradrenaline on calcium efflux. 7 The results suggest that PGF2 alpha-but not noradrenaline-induced contractions are entirely dependent on the influx of extracellular calcium and that the agonists may stimulate calcium gating mechanisms differently.

Animals↗
PubMed1982

Selective alpha 1- and alpha 2-adrenoceptor agonist-induced contractions and 45Ca fluxes in the rat isolated aorta.

1 Contractile responses produced by the alpha 1-adrenoceptor selective agonist, phenylephrine, and the alpha 2-adrenoceptor selective agonists, oxymetazoline and clonidine, have been compared to those produced by noradrenaline (non selective) in the rat aorta. 2 The relative order of potency of the agonists was noradrenaline greater than phenylephrine greater than clonidine greater than oxymetazoline. Noradrenaline and phenylephrine produced similar maximal responses. The maximal responses produced by oxymetazoline and clonidine were about 59% and 24% respectively of those produced by noradrenaline. 3 Concentrations of agonists producing maximal contractions exhibited different response-time relationships. Responses to noradrenaline and phenylephrine were biphasic while responses induced by oxymetazoline and clonidine were monophasic. 4 In calcium-free solution, contractions stimulated by oxymetazoline and clonidine were almost abolished while those stimulated by noradrenaline and phenylephrine were reduced by about 60-70%. The calcium entry blocker, cinnarizine, almost completely inhibited responses to oxymetazoline and clonidine and reduced noradrenaline- and phenylephrine-stimulated responses by about 60%. 5 All the agonists stimulated the uptake of 45Ca into the La3+-resistant Ca2+ fraction of the artery but only noradrenaline and phenylephrine stimulated the efflux of 45Ca into calcium-free solution. The 45Ca uptake stimulated by oxymetazoline and clonidine was abolished by cinnarizine and that stimulated by noradrenaline and phenylephrine was reduced by about 85%. 6 It is concluded that clonidine and oxymetazoline stimulate contractions that are totally dependent on extracellular calcium. Noradrenaline and phenylephrine stimulate contractions that are partly dependent on extracellular calcium and partly dependent on intracellular calcium stores.

Adrenergic alpha-Agonists↗
PubMed1982

A case of premature labour due to Campylobacter jejuni infection.

A case history is described in which premature labour was thought to have been caused by chorioamnionitis secondary to infection with Campylobacter jejuni. The pathogenicity of this organism in the perinatal period and in pregnancy is discussed. Campylobacter species are known to cause abortion and stillbirth in cattle and sheep. The present case report supports previous evidence that Campylobacter jejuni can cause infection in utero and perinatally in man, leading to abortion and preterm labour. Sporadic accounts of case histories similar to the present have appeared in the literature, but the incidence and epidemiology of this infection in obstetric patients is still unclear.

Adult↗
PubMed1982

Comparison of the incidence of oncogenic transformation produced by X rays, misonidazole, and chemotherapy agents.

An established line of mouse fibroblasts (10T1/2 cells) cultured in vitro was used to compare the incidence of oncogenic transformation produced by x rays, the hypoxic cell radiosensitizer misonidazole, and a range of commonly used chemotherapy agents. A 3-day exposure to misonidazole at a concentration obtainable during treatment produced an incidence of transformation similar to that of about 50 rad. When chemotherapy agents were tested at concentrations comparable to those used clinically and matched to produce similar cell killing, the incidence of transformation varied widely: some agents, such as vincristine, did not produce transformation at a level detectable above background, while others, such as cis-platinum, appear to be potent carcinogens and produce transformation at a rate orders of magnitude higher than that achieved with x rays.

Animals↗