PubMed Health⌕ Search

Biomedical subjects

J R McLean

Publications and source records attributed to J R McLean.

At least 19 recordsLinked to original sources
PubMed1992

Modification of tumor promotion in the mouse skin by exposure to an alternating magnetic field.

Some epidemiological studies have suggested that exposure to an alternating magnetic field may increase the incidence of some cancers. Our earlier study of carcinogenesis in mouse skin, indicated that exposure to a magnetic field (MF) alone did not promote the growth of tumors. In the present experiment, the ability of a MF to act as a tumor copromoter was investigated. The dorsal skins of female SENCAR mice (6-7-weeks-old) were treated with 10 nmol of 7,12-dimethylbenzanthracene (DMBA) to initiate the carcinogenic process and then tumor development was promoted, for 23 weeks, by weekly applications of 4.9 nmol (0.3 microgram) of 12-0-tetradecanoylphorbal-13-acetate (TPA). One group of 48 mice were exposed to a 60-Hz magnetic field of 2 mT (20 Gauss) for 6 h/day 5 days/week, while a similar group (48 mice) were sham exposed. After week 12, the percentage of mice with tumors and the mean number of tumors per mouse, were higher for the group exposed to MF. At week 18, for example, where the differences between field and sham groups were statistically significant, the percentage of mice with tumors were, respectively, 25% and 8% (P less than 0.05, Fisher exact) and, the mean yield of tumors 1.9 +/- 0.69 and 0.65 +/- 0.46 (mean +/- S.E.M.) (P less than 0.05, Wilcoxon). At week 23 these differences were no longer statistically significant.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Cancer promotion in a mouse-skin model by a 60-Hz magnetic field: II. Tumor development and immune response.

This paper describes preliminary findings on the influence of 60-Hz (2-mT) magnetic fields on tumor promotion and co-promotion in the skins of mice. The effect of magnetic fields on natural killer (NK) cell activity in spleen and blood was also examined. Groups of 32 juvenile female mice were exposed to the magnetic field as described in part I. The dorsal skin of all animals was treated with a subthreshold dose of the carcinogen 7,12-dimethyl-benz(a)anthracene (DMBA). One week after the treatment, two groups were sham exposed (group A) or field exposed at 2 mT (group B) 6 h/day for 21 weeks, to test whether the field would act as a tumor promoter. No tumors developed in these two groups of mice. To test whether the magnetic field would modify tumor development by directly affecting tumor growth or by suppressing immune surveillance, two additional groups of mice were treated weekly with the tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA) and then either sham exposed (group C) or field exposed (group D). The time to appearance of tumors was shorter (but not statistically so) in the group exposed to magnetic fields and TPA. Some differences in NK cell activity and spleen size were observed between the sham- and field-exposed groups.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Cloning and molecular characterization of a metabolic gene with development functions in Drosophila. I. Analysis of the head function of Punch.

In an effort to understand the functions of pterins throughout development we have been studying Punch (Pu), the structural gene for the enzyme GTP cyclohydrolase in Drosophila melanogaster. This enzyme catalyzes the first step in the pterin biosynthetic pathway. The Pu gene product is required for vital functions at two distinct stages in embryogenesis, and a pigmentation function in the eye of the young adult. We have localized the Pu region to 29 kb of DNA through the analysis of lesions present in Pu mutants. Since all of the mutations that were mapped affect the eye pigmentation function of Pu, and since this function is the best defined biochemically, we have concentrated on identifying and characterizing Pu products required for eye pigmentation in our initial examination of the cloned region. Four different transcripts from this region are expressed in the adult head. We show that one of these transcripts, the 1.7-kb species, is responsible for the pigmentation function through the analysis of mutant transcripts and the use of an in vitro translation assay. A 2-kb region lying within the locus is specifically required for this eye pigmentation function.

Animals↗
PubMed1989

Molecular and developmental genetics of the Punch locus, a pterin biosynthesis gene in Drosophila melanogaster.

Punch (Pu), the gene encoding the pterin biosynthetic enzyme GTP cyclohydrolase in Drosophila, is a complex locus. Mutations fall into several complementation classes that correspond to classes of mutants with distinct morphological and protein phenotypes. Two of these classes are developmentally specific, with mutants in each having defects in discrete subsets of the known functions of the locus. Defined functions of the locus include a role in embryonic nuclear divisions using initially a maternal Pu product, the synthesis of pterin cofactors that are required for catecholamine biosynthesis beginning in late embryogenesis, and the production of pterin-screening pigments in the developing adult eye. Mutant phenotypes include an interruption in synchronous nuclear divisions in precellular blastoderm embryos, a segment pattern phenotype in late embryos, failure to pigment and cross-link embryonic cuticular structures and failure to synthesize red eye pigments. Molecular analysis reveals that the locus is large, a minimum of 29 kb as defined by Southern mapping of Pu mutants. This region is transcriptionally extremely active, encoding at least 16 developmentally regulated transcripts. One transcript has been shown to be responsible for the production of the adult eye GTP cyclohydrolase on the basis of developmental profile, location with respect to the mapping of eye-specific Pu mutants, absence in eye-specific mutants, and hybrid-selection in vitro translation experiments. Several other transcripts are candidates for Pu vital functions, as suggested by their pattern of expression and their derivation from regions to which lethal Pu mutations map.

Animals↗
PubMed1989

The radiation dose to cells in vitro from intracellular indium-111.

Most of the radionuclides used in nuclear medicine emit low energy Auger electrons following radioactive decay. These emissions, if intracellular, could irreparably damage the radiosensitive structures of the cell. The resulting radiation dose, which is a measure of biological damage in the affected cell, could be many times the average radiation dose to the associated organ. In this series of experiments, the radiation dose to the nucleus of a chinese hamster V79 cell was determined for the intracellular radiopharmaceutical 111indium-oxine. Assuming the cell nucleus to be the radiosensitive volume, the radiation dose would be primarily due to the low energy Auger electrons. A much smaller dose would be absorbed from the penetrating X- and gamma-rays and internal conversion electrons released from other radiolabelled cells in the culture. The radiation dose to the cell from the intranuclear decay of 111In was empirically established from cell survival studies to be 3.5 mGy/decay, using cobalt-60 as a reference radiation. The average dose to V79 cells from extracellular 111In (i.e., from 111In located outside the target cell) was calculated to be 5.8 pGy/decay. This suggests that for an intracellular radiopharmaceutical, the radiation dose of consequence would be delivered by the low energy Auger electrons. In contrast, Auger electrons from an extracellular radiopharmaceutical could not directly damage the cell nucleus and therefore would not contribute to the radiation dose.

Animals↗
PubMed1989

The Auger electron dosimetry of indium-111 in mammalian cells in vitro.

Most of the radionuclides used in the formulation of radiopharmaceuticals emit Auger electrons when they undergo radioactive decay. The release of these low-energy electrons at extracellular sites produces little direct damage to intracellular structures. However, many radiopharmaceuticals, or their metabolites, can be transported into the cell where the Auger electrons have the potential to damage nearby intracellular macromolecules, including DNA. In this preliminary study, chromosome damage, expressed as 60Co equivalent doses, and the effects on cell division following treatment with intracellular and extracellular 111In were measured in Chinese hamster V79 cells. The chromosome aberration yield in cells irradiated by intracellular 111In indicated that damage was induced at a rate of 7.2 X 10(-4) Gy/decay for levels of activity up to 0.075 Bq/cell and 4.5 X 10(4) and 2.9 X 10(4) Gy/decay for intermediate (0.204 Bq/cell) and high (0.389 Bq/cell) levels, respectively. Extracellular 111In-chloride produced damage at a rate of about 6.1 X 10(-12) Gy/decay. As little as 4.4 mBq/cell (about 4.4 X 10(3) Bq/ml of culture) of intracellular 111In was able to affect cell division, whereas extracellular 111In at 1.150 MBq/ml of culture had little effect. These data indicate that the Medical Internal Radiation Dose and International Committee on Radiation Units methods for organ dosimetry may underestimate the potential of intracellular Auger electron emitters to produce radiation damage.

Animals↗
PubMed1988

A cavitation and free radical dosimeter for ultrasound.

A simple and sensitive method is described for measuring the number of hydroxyl radicals (.OH) produced in aqueous solution by high intensity ultrasound (US). The method is based on the conversion of nonfluorescent terephthalic acid (TA) to highly fluorescent hydroxyterephthalate (HTA). The spectrofluorimeter is calibrated by use of a TA solution which has been exposed to a reference dose of cobalt-60. This allows fluorescence readings produced by ultrasound to be read directly in equivalent centiGrays (cGy). The limit of detection for OH is about 1.3 X 10(-9) M (equivalent to an exposure of about 0.5 cGy of cobalt-60). The threshold for transient cavitation (TC) in an air-saturated aqueous solution was found at 0.7 watts per cm2. Cavitation was consistently produced when TA was exposed in a soft vinyl chamber and only when the chamber was being rotated about an axis which was perpendicular to the US beam. The use of TA as a quantitative indicator of transient cavitation should be of value to the study of ultrasonic biological effects and dosimetry.

Equipment Design↗
PubMed1987

Cancer risk from inorganics.

Inorganic metals and minerals for which there is evidence of carcinogenicity are identified. The risk of cancer from contact with them in the work place, the general environment, and under conditions of clinical (medical) exposure is discussed. The evidence indicates that minerals and metals most often influence cancer development through their action as cocarcinogens. The relationship between the physical form of mineral fibers, smoking and carcinogenic risk is emphasized. Metals are categorized as established (As, Be, Cr, Ni), suspected (Cd, Pb) and possible carcinogens (Table 6), based on the existing in vitro, animal experimental and human epidemiological data. Cancer risk and possible modes of action of elements in each class are discussed. Views on mechanisms that may be responsible for the carcinogenicity of metals are updated and analysed. Some specific examples of cancer risks associated with the clinical use of potentially carcinogenic metals and from radioactive pharmaceuticals used in therapy and diagnosis are presented. Questions are raised as to the effectiveness of conventional dosimetry in accurately measuring risk from radiopharmaceuticals.

Animals↗
PubMed1987

Neuropharmacology of zonisamide, a new antiepileptic drug.

Zonisamide readily crosses the blood-brain barrier and is readily absorbed after oral administration with a Tmax of about 3 hr. The half-life of ZNA in epileptic patients is about 28 hr. Zonisamide has a broader therapeutic range than other antiepileptic drugs. Neurotoxic, hemapoietic, renal, and liver effects have been minimal in patients participating in controlled clinical studies. It is effective in several experimental models of epilepsy and in initial clinical trials has been shown to be effective in generalized tonic-clonic, simple, and complex partial seizures.

Animals↗
PubMed1986

Comparative pharmacokinetics of zonisamide (CI-912) in epileptic patients on carbamazepine or phenytoin monotherapy.

Zonisamide (CI-912) is an experimental antiepileptic drug. Since this drug is to be evaluated initially as an add-on medication, an investigation was conducted to study its kinetics in the presence of two standard antiepileptic drugs. Patients in two groups, one on maintenance phenytoin (PHT) monotherapy and the other on maintenance carbamazepine (CBZ) monotherapy, each received a single dose of four 100-mg capsules of zonisamide; and blood samples were obtained at periodic intervals. Plasma and red blood cell (RBC) concentrations of zonisamide were measured by high performance liquid chromatography. Plasma and RBC areas under the curve produced by single doses of zonisamide in patients receiving CBZ were significantly higher than those receiving PHT (p less than 0.05). Clearance values, although not statistically significantly different, were lower for the CBZ group; and consistent with this, plasma and RBC concentrations decreased more rapidly in the PHT group. The approximate values for t1/2 were 36.4 h in plasma and 54.2 h in RBC for patients treated with CBZ, and 27.1 h in plasma and 35.8 h in RBC for patients treated with PHT. The RBC/plasma ratio varied eightfold within a given curve. These findings suggest that the dosage of zonisamide in epileptic patients might need to be varied depending on the comedication.

Adolescent↗
PubMed1986

An in vitro study of the pharmacological and electrophysiological properties and the adrenergic innervation of small pulmonary arteries from children with pulmonary hypertension.

A study was made of the pharmacological and electrophysiological properties of pieces of small intrapulmonary arteries (100-450 micron I.D.) taken from children with cardiac defects that caused the pulmonary circulation to be exposed to an abnormally high perfusion pressure. The sensitivity of the arterial smooth muscle to the constrictor agonists acetylcholine and 5-hydroxytryptamine was similar to that reported for adult pulmonary arteries. Norepinephrine or histamine caused little or no constriction, although both these substances have been reported to be powerful constrictors of adult pulmonary arteries. The electrophysiological properties were similar to those of the smooth muscle of systemic arteries. The mean resting membrane potential was -6.12 mV +/- 1.29 (SEM n = 16). Stimulation of the perivascular nerves produced excitatory junction potentials, but no smooth muscle action potentials were recorded. Histochemical investigation revealed catecholamine containing nerve fibres around all intrapulmonary arteries down to 40 micron I.D.

Acetylcholine↗
PubMed1985

Catecholamine-containing neurons and lymphoid cells in a lacrimal gland of the pigeon.

The Harderian gland of birds, a major lacrimal gland, contains a large population of lymphoid cells that produce IgA, a significant component of tears. Using histochemical techniques, we have examined the innervation of the gland. There was an extensive acetylcholine-esterase positive fiber network throughout the gland. However, catecholamine positive fibers were seen mainly associated with peripheral blood vessels and the lymphoid cell population which contained autofluorescent plasma cells. Ultrastructural examination showed that vesicle filled nerve varicosities were often seen near plasma cells and that some of these varicosities reacted positively for catecholamines. These anatomical data suggest that the lymphoid cell population may be affected by the autonomic nervous system.

Acetylcholinesterase↗
PubMed1985

The adrenergic innervation of pulmonary vasculature in the normal and pulmonary hypertensive rat.

It would appear that susceptibility to chronic proliferative pulmonary hypertension in response to chronic alveolar hypoxia is most severe in species in which adrenergic innervation of pulmonary arteries is reduced or lacking. Intrapulmonary arteries of the rat have been reported to lack adrenergic innervation by some workers but not others. Since the rat develops severe proliferative pulmonary hypertension in response to prolonged alveolar hypoxia, the different divisions of the lung vasculature of Sprague-Dawley rats were thoroughly examined to determine the presence or absence of an adrenergic innervation. The degree of innervation in normal rats was compared with that of rats developing pulmonary hypertension. Both in normal and experimental pulmonary hypertensive rats the pulmonary arteries, all their branches and the small pulmonary veins with a smooth muscle media were found to be devoid of adrenergic innervation. In contrast, the cardiac-like muscle in the media of large pulmonary veins, the bronchial arteries and the vasa vasorum of larger vessels were richly innervated by adrenergic nerves. Thus the increase in medial smooth muscle which occurs in pulmonary arteries during chronic alveolar hypoxia is independent of a pre-existing adrenergic innervation or of such an innervation newly derived from that of adjacent vessels or structures. This is in contrast to systemic vessels where it has been suggested that increased adrenergic activity and density of innervation may augment hypertrophy of the media in hypertensive animals. Adrenergic nerves are suggested to have a protective action on pulmonary vessels.

Adrenergic Fibers↗
PubMed1978

Rapid assay for total unbound Tc-99m in preparations of Tc-99m in macroaggregated albumin: concise communication.

A rapid economic filter-paper assay for determining total unbound Tc-99m in preparations of Tc-99m macroaggregated albumin (Tc-99m MAA) is described. The procedure uses Whatman 542 filter-papter discs and aqueous 0.009% NaCl as wash solution. The principal radiochemical impurities found in Tc-99m MAA kits are not significantly adsorbed to the filter matrix. The procedure can be completed in 1--2 min and gives results comparable to those obtained by the centrifuge assay (USP XIX).

Albumins↗