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Biomedical subjects

R C Miller

Publications and source records attributed to R C Miller.

At least 127 records · Page 7Linked to original sources
PubMed1991

Oncogenic transformation of C3H 10T1/2 cells by acute and protracted exposures to monoenergetic neutrons.

An in vitro assay was used to assess cell killing and induction of neoplastic transformation in C3H 10T1/2 cells exposed to X rays and a range of monoenergetic neutrons administered at various dose rates. Curves for cell survival and induction of neoplastic transformation showed nonlinearity for cells exposed to acute graded doses of X rays, while irradiation of cells with 0.05 to 1.5 Gy of 0.23-, 0.35-, 0.45-, 0.70-, 0.96-, 5.90-, and 13.7-MeV neutrons resulted in a linear response as a function of dose for both neoplastic transformation and killing. When compared to results obtained with 250-kVp X rays, all neutron energies were more effective at both cell killing and induction of neoplastic transformation. When expressed as maximum biological effectiveness (RBEM), both cell survival and induction of neoplastic transformation showed an initial increase with neutron energy (maximal at 0.35 MeV), followed by a decrease in effectiveness with further increases in energy. These responses are consistent with microdosimetric predictions in that recoil protons from neutron interaction are shifted to lower lineal energies as neutron energies increase. To examine the effects of temporal distribution of dose on neutron-induced neoplastic transformation, cells were exposed to either a single dose or five equal dose fractions spread over 8 h. As a function of dose for single or fractionated exposures to 0.5 Gy or 0.23-, 0.35-, 0.45-, 5.9-, or 13.7-MeV neutrons, neither a sparing nor an enhancing effect was seen with survival. Similarly, the frequency of induction of neoplastic transformation was independent of dose fractionation for all but 5.9-MeV neutrons. The enhancing effects of exposure to fractionated doses of 5.9-MeV neutrons were further studied by comparing exposures for a range of doses given singly, in five fractions over 8 h, or continuously for 8 h. Results reaffirm the enhancing effects of dose fractionation on the induction of oncogenic transformation for 5.9-MeV neutrons. Within the limits of the data, there is modest enhancement of neutron-induced neoplastic transformation when the exposure dose is extended from a few minutes to several hours, with the enhancement being dependent on neutron energy.

Animals↗
PubMed1991

Neoplastic transformation and the inverse dose-rate effect for neutrons.

Considerable evidence has recently accumulated, both in vivo and in vitro, to suggest that neutrons at low dose rates, or in multiple fractions, have an enhanced effectiveness for inducing neoplastic transformation. A consistent pattern has emerged as to the dependence of the effect on dose, dose rate, and radiation type. A consistent model of the phenomenon as a function of dose, dose rate, and radiation type is presented. The approach, first suggested by Rossi, is that cells are extra sensitive in part of their cycle. Then an acute exposure of cycling cells to high-LET radiation results in some fraction of the sensitive cells receiving large depositions of energy--greater than required for the effect. If the exposure is protracted, a larger proportion of sensitive cells will be exposed, but to smaller numbers of energy depositions--still enough, however, to produce the effect. The model produces results consistent with all available data on enhancement of neoplastic transformation in the C3H 10T1/2 system by protraction or fractionation at medium or high LET. Implications for radiation protection and the radon problem are discussed.

Animals↗
PubMed1991

The postmenopausal palpable ovary syndrome. A retrospective review with histopathologic correlates.

Since its introduction in 1971 and based on experience with three patients, the postmenopausal palpable ovary (PMPO) syndrome has been widely accepted as appropriate justification for exploratory celiotomy to rule out ovarian malignancy. However, reports on only two small series have been published that address the incidence of malignancy in these patients. From March 1982 to June 1986, 20 patients underwent surgical exploration at the Naval Hospital, Bethesda, to evaluate an asymptomatic PMPO. Thirteen patients (60%) were found to have an ovarian neoplastic process. Three of the neoplasms were malignant or of borderline malignant potential, resulting in an overall malignancy rate of 15% for the PMPO syndrome. In comparing the PMPO groups, patients in the malignancy group had a statistically significant lower mean parity and greater mean number of postmenopausal years (P = .02 and .03, respectively). When the PMPO group was compared to patients with adnexal masses larger than 5 cm, there were no significant differences in the malignancy rates (15% versus 25%, P = .26), but the power was low. The data suggest that the PMPO syndrome may be clinically important. Additional studies to compare ultrasound, CA-125 and pelvic examination are indicated.

Aged↗
PubMed1991

Relative cataractogenic effects of X rays, fission-spectrum neutrons, and 56Fe particles: a comparison with mitotic effects.

The eyes of Sprague-Dawley rats were irradiated with doses of 2.5-10 Gy 250-kVp X rays, 1.25-2.25 Gy fission-spectrum neutrons (approximately 0.85 MeV), or 0.1-2.0 Gy 600-MeV/A 56Fe particles. Lens opacifications were evaluated for 51-61 weeks following X and neutron irradiations and for 87 weeks following X and 56Fe-particle irradiations. Average stage of opacification was determined relative to time after irradiation, and the time required for 50% of the irradiated lenses to achieve various stages (T50) was determined as a function of radiation dose. Data from two experiments were combined in dose-effect curves as T50 experimental values taken as percentages of the respective T50 control values (T50-% control). Simple exponential curves best describe dose responsiveness for both high-LET radiations. For X rays, a shallow dose-effect relationship (shoulder) up to 4.5 Gy was followed at higher doses by a steeper exponential dose-effect relationship. As a consequence, RBE values for the high-LET radiations are dose dependent. Dose-effect curves for cataracts were compared to those for mitotic abnormalities observed when quiescent lens epithelial cells were stimulated mechanically to proliferate at various intervals after irradiation. Neutrons were about 1.6-1.8 times more effective than 56Fe particles for inducing both cataracts and mitotic abnormalities. For stage 1 and 2 cataracts, the X-ray Dq was 10-fold greater and the D0 was similar to those for mitotic abnormalities initially expressed after irradiation.

Animals↗
PubMed1991

Oncogenic transformation following sequential irradiations with monoenergetic neutrons and X rays.

Mouse C3H 10T1/2 cells were exposed sequentially to low doses (0.1 and 0.3 Gy) of monoenergetic neutrons (0.35, 0.45, 5.9, and 13.7 MeV) and 250-kVp X rays (1 and 3 Gy). The incidences of oncogenic transformation in the cells exposed to neutrons followed by X rays indicated that the effects of the individual radiations were simply additive. This supports the contention that risks associated with the two different radiation modalities may be considered to be additive.

Animals↗
PubMed1990

The tertiary structure of a bacterial cellulase determined by small-angle X-ray-scattering analysis.

CenA from Cellulomonas fimi is a beta-1,4-endoglucanase that binds tightly to cellulose. X-ray-scattering analyses show that the enzyme is tadpole-shaped: the previously identified catalytic and cellulose-binding domains comprise the head and tail respectively. It appears that this structural and functional organization is common to several cellulases from bacteria and fungi.

Actinomycetales↗
PubMed1990

Radiosensitivity of skin fibroblasts from atomic bomb survivors with and without breast cancer.

Fibroblasts were established in vitro from skin biopsies obtained from 55 women and 1 man with or without breast cancer and with or without exposure to radiation from the atomic bomb explosion in Hiroshima. The radiosensitivity of these cells was evaluated by clonogenic assays after exposure to X-rays or to fission neutrons from a 252Cf source. Data were fitted to a multitarget model, S/S0 = A [1 - (1 - ekD)N], for both X-ray and neutron dose-survival curves. A single hit model, S/S0 = AekD, fits the neutron dose-survival responses as well. There were no differences in the means or variances of radiosensitivity between exposed and nonexposed groups or between patients with or without breast cancer. Hence, although the sample is not large, it provides no support for the hypothesis that atomic bomb radiation preferentially induces breast cancer in women whose cells in vitro are sensitive to cell killing by radiation.

Adolescent↗
PubMed1990

Endothelin: a review of its effects and possible mechanisms of action.

The recently identified endothelium-derived peptide, endothelin, is a potent vasoconstrictor, but also binds specifically to many types of smooth muscle and to nerve tissue. Endothelin has been detected in plasma and may have physiological or pathological functions. Like other agonists, endothelin increases the turnover of phosphatidyl inositol and liberates intracellular stocks of Ca2+. It also increases plasmalemmal Ca2+ permeability, an effect that is antagonized by calcium entry blockers in some tissues. However, the characteristics of this antagonism are not always typical of that seen when other types of agonists are employed. It seems that in at least some cell types endothelin might activate specific L-type Ca2+ channels indirectly, perhaps secondarily to the activation of another type of cation channel. The endothelin originally described is one of a family of peptides that are closely related to the sarafotoxins. The comparative pharmacology of these peptides and of some analogues of the originally described endothelin have revealed some surprising differences and may indicate the existence of different endothelin receptors.

Amino Acid Sequence↗
PubMed1990

Prenatal diagnosis of laryngeal atresia.

In a patient in whom preeclampsia developed at 23 weeks' gestation, ultrasonographic examination of the fetus showed enlarged edematous lungs, a compressed fetal heart, severe ascites, fetal hydrops, and placental edema. Autopsy of the hydropic stillborn infant showed laryngeal atresia. The ultrasonographic appearance of this rare malformation is presented.

Adult↗
PubMed1990

Infectious crystalline keratopathy.

A 76-year-old patient was found to have a crystalline keratopathy with no evidence of acute inflammation in her right corneal graft. The patient had been on long-term topical steroids. Subsequent microscopy of the graft demonstrated pockets of Gram-positive cocci with a paucity of inflammatory cells. This is the tenth reported case of infectious crystalline keratopathy, first reported by Gorovoy in 1983. It does not always occur in corneal grafts, but the use of long-term topical steroids, together with an epithelial defect, allows the microorganism, usually Streptococcus viridans, to invade the corneal stroma and replicate along the lamellar planes, unhindered by the usual inflammatory response. Retrospective analysis of this patient's history suggests that she has suffered the same keratopathy in previous corneal grafts. Treatment involves cessation of steroids, antibiotic cover and often a repeat penetrating keratoplasty. If this is required, the lowest possible dose of steroid cover should be used with prolonged use of topical antibiotics. To the best of our knowledge this is the first reported case of infectious crystalline keratopathy in Australia.

Aged↗
PubMed1990

Binding of [125I]-endothelin-1 to rat cerebellar homogenates and its interactions with some analogues.

1. [125I]-endothelin-1, over the concentration range 6 pM-10 nM, bound to a single site in homogenates of rat cerebellum with high affinity (Kd = 2.8 +/- 0.6 x 10(-10) M). The site was present in a concentration of 321 +/- 58 fmol mg-1 protein. 2. The rates of association and dissociation of [125I]-endothelin-1 with the binding site were slow (at 25 degrees C, k+1 = 8.0 +/- 1.3 x 10(5) M-1s-1; k-1 = 2.6 x 10(-4)s-1) and, on addition of a maximally displacing concentration of endothelin-1 (100 nM), 94.0 +/- 8.4% of the [125I]-endothelin-1 was still bound after 14 h. 3. [125I]-endothelin-1 binding was inhibited by a number of naturally occurring or genetically encoded members of the endothelin/sarafotoxin family of peptides. The order of potency was endothelin-3 = sarafotoxin S6b greater than endothelin-2 = endothelin-1 much greater than porcine proendothelin1-39. 4. Binding was also inhibited by analogues in which either one or both of the cystine disulphide bridges had been replaced by substitution with 2 or 4 alanine residues. The tetra-alanyl substituted analogue, [Ala1,3,11,15]endothelin-1, was equipotent with endothelin-1 at inhibiting the binding of [125I]-endothelin-1. [Ala3,11]endothelin-1 and [Ala1,15]endothelin-1, analogues which each contained one of the disulphide bridges from the parent peptide, were respectively 3 and 14 times less potent than the parent peptide. An analogue in which the Glu10 residue had been anisylated was 25 fold less potent than endothelin-1. 5. It is concluded that the structural requirements for binding to the cerebellar sites for [1251]_ endothelin-1 do not require the presence of the disulphide bridges characteristic of the endothelin/ sarafotoxin family. Rather, the binding may be more sensitive to the presence of bulky side chain substituents, at least in the smaller intramolecular loop.

Animals↗
PubMed1990

The effects of the temporal distribution of dose on oncogenic transformation by neutrons and charged particles of intermediate LET.

The effects of dose rate and dose fractionation on high-LET radiation-induced oncogenic transformation of C3H 10T1/2 cells were examined. Cells were irradiated with graded doses of 5.9-MeV monoenergetic neutrons administered either in single acute exposures (30 mGy/min) or extended over an 8-h period at low dose rates (from 0.21 to 1 mGy/min). Although cell survival studies showed no difference in effect with a change in radiation delivery rate, enhancement of oncogenic transformation occurred when the dose rate was reduced. When the neutron dose was divided into three fractions over 8 h, the biological effect was intermediate between that for the acute and that for the low-dose-rate exposures. Further irradiations were made using deuterons with an LET of 40 keV/microns. The dose-mean lineal energy was comparable to that measured for the 5.9-MeV monoenergetic neutrons. An inverse dose-rate/fractionation effect for the induction of transformation by high-LET deuterons was observed when the time between each of three fractions for a 0.3-Gy total dose was at least 45 min. No further enhancement was seen for longer dose fractionations, suggesting that very long protracted exposures of high-LET radiation would produce no additional enhancement.

Animals↗
PubMed1989

Structural and functional analysis of a bacterial cellulase by proteolysis.

CenA is an endo-beta 1,4-glucanase from the cellulolytic bacterium Cellulomonas fimi. It is a bifunctional enzyme comprising an amino-terminal cellulose-binding domain and a carboxyl-terminal catalytic domain joined by a short sequence of prolyl and threonyl residues (the Pro-Thr box). Additional structural and functional information was revealed by a detailed analysis of the products generated by proteolytic cleavage of a nonglycosylated form of CenA. An extracellular C. fimi protease attacked nonglycosylated CenA at the junctions between the Pro-Thr box and the two functional domains. A stable "core" peptide (p30), corresponding to the catalytic domain, remained after extensive proteolysis. p30 was resistant to further attack even in the presence of 2-mercaptoethanol plus urea or dithiothreitol, but treatment in the presence of sodium dodecyl sulfate allowed complete fragmentation to small peptides. Stable peptides, identical, or closely related to p30, were generated by alpha-chymotrypsin or papain. These results indicated that the catalytic domain adopts a tightly folded conformation affording protection from proteolytic attack. In contrast, the cellulose-binding domain showed a relatively loose conformation. Progressive proteolytic truncation from the amino terminus was apparent during incubation with alpha-chymotrypsin or papain, or with C. fimi protease under reducing conditions. Affinity for cellulose was retained by products missing up to 64 amino-terminal amino acids. The remaining carboxyl-proximal region of the cellulose-binding domain with affinity (47 amino acids) contained sequences highly conserved in analogous domains from other bacterial endo-beta 1,4-glucanases. By analogy with other systems, the properties of the Pro-Thr box are consistent with an elongated conformation. The results of this investigation suggest that CenA has a tertiary structure which resembles that of certain fungal cellulases.

Amino Acid Sequence↗
PubMed1989

Autoradiographic localisation of endothelin binding sites in kidney.

[125I]Endothelin binding sites occurred in glomeruli of human, monkey, rat and dog kidney but not rabbit glomeruli. The renal medulla had more binding sites in all species, with the greatest densities of all in the rat and monkey renal papillas. Binding in rat kidney was inhibited by [Ala3,11]endothelin with lower potency than endothelin but not by unrelated peptides. These binding sites may represent the endothelin receptors and suggest actions for endothelin on renal function.

Animals↗
PubMed1989

Fusion to an endoglucanase allows alkaline phosphatase to bind to cellulose.

Endoglucanase CenA of Cellulomonas fimi comprises an N-terminal cellulose-binding domain and a C-terminal catalytic domain joined together by a sequence of 23 proline and threonine residues (the Pro-Thr box). The domains function independently when separated by proteolysis. TnphoA has been used to generate cenA'-'phoA fusions. CenA'-'PhoA fusion polypeptides which contain the entire cellulose-binding domain of CenA bind to cellulose, allowing their purification from periplasmic extracts in a single, facile step. This result has implications for purification or immobilisation of chimeric proteins on a cheap cellulose matrix.

Actinomycetales↗