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Biomedical subjects

D J Mitchell

Publications and source records attributed to D J Mitchell.

At least 73 records · Page 4Linked to original sources

Hyperplastic and neoplastic changes in the mammary glands of feral mice free of endogenous mouse mammary tumor virus provirus.

Laboratory colonies of feral mice (Mus musculus domesticus) have been established with specific mouse mammary tumor virus (MuMTV) genotype, including colonies lacking any proviral DNA (ev-) or carrying only a single copy of MuMTV DNA (ev+). No evidence of a decline in reproductive capacity has been observed in the first 8 generations. Both the ev- and ev+ mice showed normal mammary gland development and the development of hyperplastic lesions in the older females. The mice were very resistant to spontaneous or chemically induced mammary tumors. However, the occurrence of 1 mammary tumor in an ev- mouse indicates that mammary neoplasias can occur in the absence of MuMTV DNA. The few tumors that do occur in the ev- mice provide a unique opportunity to study the neoplastic process in the absence of proviral DNA.

Animals↗

Effect of dietary fat on tumorigenesis in the mouse mammary gland.

The effects of dietary polyunsaturated fat in BALB/c mice were determined for several stages of mammary tumorigenesis: a) growth of intact and transplanted normal mammary tissue, b) growth of hyperplastic alveolar nodule (HAN) lines D1/ UCD and Z5C1 , c) incidence of tumors occurring in D1/ UCD , and d) growth rate of the tumors. Growth of transplanted normal mammary epithelium as well as intact glands was faster in mice fed a 10% corn oil (CO) diet, which contains linoleate, than in those fed 10% hydrogenated cottonseed oil ( HCTO ), a diet free of the polyunsaturated fatty acid. We concluded that transplantation itself does not alter the response of mammary tissue to dietary fat. The growth of both HAN lines was unchanged by the presence of CO in the diet. For ascertainment as to whether the difference in response was specific to the tissue, ducts and HAN line D1/ UCD were transplanted into left and right gland-free fat pads of the same mice. The duct tissue grew faster when the hosts were fed the 10% CO diet than in the hosts fed the 10% HCTO diet; however, no effect of dietary fat was noted with the HAN. Although indomethacin retarded the growth of normal tissue in the mice fed CO diet, this prostaglandin inhibitor had no effect on the growth of the HAN transplants. Both incidence and growth rate of tumors arising from transplants of HAN line D1/ UCD were greater in mice fed diets containing either 0.3, 1, or 10% CO than in those fed 10% HCTO . The smaller number of tumors arising in mice fed with 10% HCTO diet may be the result of the slower growth rate of the neoplasms in mice fed diets devoid of linoleate.

Animals↗

Effects of X irradiation on the growth of normal and hyperplastic mouse mammary gland transplants.

To avoid the problems associated with whole-body radiation, pieces of X-irradiated normal or hyperplastic mammary tissue were transplanted to the host gland-free fat pad of nonexposed mice. The percentage of the fat pad filled by growth of the transplants at 4, 8, and 12 weeks after transplantation was measured. Growth of lobule transplants was moderately inhibited by 4 Gy. While some of the lobules survived 12 Gy, their growth was severely inhibited. The hyperplastic outgrowth lines were variable but more resistant than lobules to growth retardation. Line Z5D was more susceptible than D1, and Z5C1 was least susceptible, with 88% growing well after 12 Gy. In order to distinguish between transient and permanent growth retardation, tissue was taken from the irradiated and control transplants and retransplanted to new hosts without further radiation. The second generation of X-ray-exposed tissue filled more of the fat pad than the first-generation transplants, but significantly less than the nonexposed controls. The experiments described provide a means of demonstrating X-ray-induced changes in the mammary gland from growth inhibition to carcinogenesis.

Animals↗

Survival of mouse mammary gland transplants of normal, hyperplastic, and tumor tissues exposed to X-rays.

Mouse mammary tissues, including ducts, prelactating lobules, hyperplastic outgrowth lines, and tumors, were exposed to varying doses of X-rays and then transplanted to fat pads of nonirradiated BALB/c mice for study. Estimates of the dose of radiation that would allow survival of 50% of the transplants (SD50) were made with the use of probit analysis. Nearly all duct and lobule transplants survived doses of X-rays from 0 to 800 rad. The survival rate declined rapidly following doses above 800 rad, and the calculated SD50 was 1,020 and 1,260 rad for mammary ducts and lobules, respectively. The three hyperplastic outgrowth lines tested gave very different results. Hyperplastic line Z5C1 transplants had better than 90% survival at doses up to 1,200 rad and an SD50 between 1,200 and 1,600 rad. Hyperplastic line Z5D transplants had an SD50 of between 800 and 1,200 rad. Hyperplastic line D1 transplants had a better than 90% survival following doses of 0-600 rad and an SD50 between 600 and 800 rad. The survival of tumor transplants was 100% following doses of X-rays up to 1,200 rad; the SD50 was in excess of 1,600 rad. The mouse mammary transplantation system can be used to study the direct effect of X-rays on normal, premalignant, and malignant mammary tissues and provides a basis for the study of the radiobiology of mammary tissues.

Animals↗

Development and characterization of mouse hyperplastic mammary outgrowth lines from BALB/cfC3H hyperplastic alveolar nodules.

Five hyperplastic outgrowth lines were developed by serial transplantation of hyperplastic alveolar nodules from BALB/cfC3H mice into BALB/c hosts. The lines were used to study the biology, morphology, and virology of premalignant tissue originating in mouse mammary tumor virus (MuMTV)-positive animals. The five lines differed with respect to tumor potential and growth characteristics, corroborating the previous evidence that MuMTV-positive hyperplastic alveolar nodules are biologically heterogeneous. Subgross and microscopic examination of outgrowths and tumors revealed that each line had unique morphological characteristics. The presence of atypical lobules within the hyperplastic outgrowth appeared to be correlated with tumor risk, and a morphological continuum of atypical lesions ending in overt cancer was suggested. Viral expression was detected by nucleic acid hybridization and immunoperoxidase staining for MuMTV structural antigens. While the MuMTV RNA in certain tissues appeared to vary qualitatively with tumor potential of the outgrowth line, no correlation between viral antigens detected by immunoperoxidase staining and tumor potential was observed.

Animals↗

Theory of self-assembly of lipid bilayers and vesicles.

A simple theory is developed that explains the formation of bilayers and vesicles and accounts quantitatively for many of their physical properties: Properties including vesicle size distributions and bilayer elasticity emerge from a unified theory that links thermodynamics, interaction free energy, and molecular geometry. The theory may be applied to the analysis of more complicated membrane structures and mechanisms.

Liposomes↗

Phase transition in charged lipid membranes.

Experimental results on the effect of electrostatics on bilayer phase transitions are compared with corresponding data for monolayers and the predictions of electrical double layer theory. The two substantial conclusions which emerge are that: (i) double layer theory based on a continuous surface charge distribution cannot explain all the relevant data, a situation which may be improved by taking into account the discrete nature of the surface charge distribution; (ii) the crystal - liquid crystal phase transition of charged bilayer membranes is always a continuous one which takes place through an intermediate state consisting of both fluid and frozen domains.

Electricity↗

The genetic control of DS-RNA virus-like particles associated with Saccharomyces cerevisiae killer yeast.

Previous results have indicated that laboratory strains of yeast possessing two types of dsRNA virus-like particles, V1 and V2, are capable of producing a killer toxin which kills sensitive strains. This paper reports on genetic crosses which correlate the presence of these particles both with a host nuclear gene +/-/mak1 and with the production of a killer toxin. The results show that: (i) V1 particles are inherited independently of the +/-/mak1 gene. (ii) V2 particles are present only in combination with those of V1 and the +/- allele of the +/-/mak1 nuclear gene.

Alleles↗

A model for the packing of lipids in bilayer membranes.

A number of known structural properties of mixed lipid bilayer membranes and monolayers are accounted for by a model in which lipids pack into bilayers and monolayers like building blocks, each characterized by a surface head group area and characteristic solid angle. In phospholipids above the melting transition the head group area (at a given temperature and degree of hydration) is fairly invariant while the hydrocarbon region may be liquid-like so long as the molecule is not compressed beyond its characteristic solid angle. Phosphatidylcholine and phosphatidylserine are tapered lipids, i.e. their surface head group areas are greater than their non-polar end areas; cholesterol is frayed, i.e. its polar end area is less than its non-polar end area; while phosphatidylethanolamine is almost cylindrical. The "condensing" effect of cholesterol in mixed phospholipid-cholesterol films is seen as a taper-fray accommodation. The lipid distribution in erythrocyte membrane is shown to be conducive to a stable strain-free membrane.

Cholesterol↗

Obituaries:.

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History, 20th Century↗

Oil myelography.

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Humans↗

Van der Waals forces between cylinders. II. Retarded interaction between thin isotropic rods.

We derive the retarded van der Waals interaction between two long thin parallel dielectric cylinders immersed in a solvent. The result shows that the ultraviolet interactions which may be responsible for the specificity of macromolecular interactions do not operate strongly over distances R >/= 50 A. For greater distances the contribution of these frequencies xi is damped by a factor infinity e(-xiR/c).

Macromolecular Substances↗