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D N Slatkin

Publications and source records attributed to D N Slatkin.

At least 73 records · Page 4Linked to original sources

DNA concentrations in the human cerebellum. Computation from kinetics of deoxyribose extraction in hot acid.

DNA can be measured in mammalian tissues by extracting deoxyribose from unfixed, lyophilized tissue specimens with 0.5 N perchloric acid at 90 degrees C. Deoxyribose concentrations in the extract are determined photometrically by reaction with diphenylamine. Inevitably, some deoxyribose is destroyed during exposure to the hot acid. A computer program has been written which corrects photometric absorbance data for such loss of deoxyribose. When extrapolated to infinite duration of extraction, the corrected absorbances yield a measure of the DNA content of the specimen. This method was used to estimate DNA concentrations in human cerebellar cortex and white matter. The results are discussed in relation to stable carbon isotope ratios of human cerebellar DNA.

Cerebellar Cortex↗

Protection of mice from whole-body gamma radiation by deuteration of drinking water.

Drinking water made available to mice was changed from ordinary tap water to tap water containing 30 atom% D2O when the animals were 6 to 8 weeks old. Twelve days later, the deuterated mice and an approximately equal number of nondeuterated control mice were subjected to whole-body gamma radiation from a 60Co source. All mice received ordinary tap water after the irradiation. Postirradiation mortality was significantly less in deuterated than in nondeuterated animals. These results may have practical implications for radiotherapy of human malignant tumors.

Animals↗

Melanin content of hamster tissues, human tissues, and various melanomas.

Melanin content (percentage by weight) was determined in both pigmented and nonpigmented tissues of Syrian golden hamsters bearing Greene melanoma. Melanin content was also measured in various other melanoma models (B-16 in C57 mice, Harding-Passey in BALB/c mice, and KHDD in C3H mice) and in nine human melanomas, as well as in selected normal tissues. The purpose was to evaluate the possible efficacy of chlorpromazine, which is known to bind to melanin, as a vehicle for boron transport in neutron capture therapy. Successful therapy would depend upon selective uptake and absolute concentration of borated compounds in tumors; these parameters will in turn depend upon melanin concentration in melanomas and nonpigmented "background" tissues. Hamster whole eyes, hamster melanomas, and other well-pigmented animal melanomas were found to contain 0.3 to 0.8% melanin by weight, whereas human melanomas varied from 0.1 to 0.9% (average, 0.35%). Other tissues, with the exception of skin, were lower in content by a factor of greater than or equal to 30. Melanin pigment was extracted from tissues, and the melanin content was determined spectrophotometrically. Measurements were found to be sensitive to the presence of other proteins. Previous procedures for isolating and quantifying melanin often neglected the importance of removing proteins and other interfering nonmelanic substances.

Animals↗

Natural 13C/12C ratio variations in human populations.

Baseline data on the naturally occurring 13C/12C ratios of human tissue samples from several modern human populations are presented. Isotope ratios were determined for endogenous tissue samples (brain, liver and lung) from 20 routine unselected autopsy cases of residents of Long Island, New York. Comparable data were obtained from tissue samples from Bergen, Norway and Lucerne, Switzerland. Average values of 13C ratios reported in units of delta13C(0/00) relative to the PDB carbonate standard were -20.6 +/- 1.0 for 49 tissue samples from Switzerland, -20.7 +/- 1.0 for 21 tissue samples from Bergen, Norway and -16.2 +/- 1.0 for 89 tissue samples from Long Island, New York. These variations are discussed in terms of the isotopic carbon inventory in the respective diets of the populations sampled and also in terms of their implications for biomedical investigation.

Autopsy↗

The 13C/12C ratio in black pulmonary pigment: a mass spectrometric study.

Ratios of the two stable isotopes of carbon, 13C and 12C, were measured in black pulmonary pigment and in several endogenous tissues removed during 20 autopsies on Long Island, New York. The mass spectrometer used for carbon isotope ratio analyses has a precision of +/- 1 13C atom per million carbon atoms. The 13C/12C ratio was found to be distinctly lower in black pulmonary pigment than in endogenous tissues, the mean difference amounting to 65 13C atoms per million carbon atoms. The results demonstrate that the elemental carbon fraction of black pulmonary pigment is exogenous and constitutes roughly 30 per cent of the weight of the pigmented material. It was also observed that 13C/12C ratios in endogenous tissues from individual autopsy cases were not quite identical, tending to be slightly greater in corpus callosum than in liver or peripheral lung.

Aged↗

Intramyofiber metastases in skeletal muscle.

Autopsy examination in a case of metastatic carcinoma revealed psoas muscle invasion with nests of tumor cells within individual myofibers. Such findings suggest that there is an intracellular route for the spread of malignant tumor in skeletal muscle.

Carcinoma, Small Cell↗

Optimization of boron and neutron delivery for neutron capture therapy.

A number of groups in the United States have received funding that will permit evaluation of the clinical efficacy of the neutron capture therapy (NCT) procedure. Various reactors are being modified to allow the construction of an epithermal neutron beam. At the Brookhaven Medical Research Reactor (BMRR), the patient irradiation facility is being modified to produce an optimized epithermal neutron beam. An 80-cm-thick A1-D2O mixture (184 g/cm2, 25% D2O by volume) is being installed in the shutter assembly. One-dimensional calculations indicate that this configuration should provide an epithermal neutron flux density of approximately 1 x 10(9) n/cm2/sec at 3 MW and a concomitant fast neutron dose rate of approximately 2 x 10(-11) rad per epithermal neutron (assuming a homogeneous A1-D2O mixture). The actual geometry will be an inhomogeneous array of D2O and A1 layers producing parameters somewhat less favorable than those listed above; experimental verification is in progress. Significant gains have recently been made in selectively targeting B to melanoma with various melanaffinic compounds, including p-boronophenylalanine, and with boronated porphyrins that may be applicable to a variety of tumors. Neutron capture radiographs have been obtained with the above compounds, and efforts have been made to quantitate boron uptake in growing and quiescent or necrotic regions of tumor via double-labeling techniques obtained with tritiated thymidine. A correlation between therapeutic efficacy and the ability to deliver boron to viable areas of tumor has been observed.

Animals↗

Feasibility of noninvasive analysis of lead in the human tibia by soft x-ray fluorescence.

A postmortem study was conducted to assess the feasibility of measuring bone lead concentrations noninvasively in vivo. Characteristic L x rays were induced with an external source of 125I in the superficial tibial cortex of the intact legs of six adults who had no history of occupational exposure to lead. Tibial lead concentrations in the same bones subsequently determined by flameless atomic absorption spectroscopy varied from 15 to 35 micrograms Pb/g wet weight. The upper limit for the modern normal range of lead in the bone is about 25 mg Pb/g wet tissue. The linear correlation coefficient (r) between the measurements made with x-ray fluorescence and lead concentration by absorption spectroscopy was 0.90. Radiation doses of 10 mGy (1 rad) to 1 cm2 of skin, with associated doses to the marrow of adjacent bone of about 0.6 mGy (60 mrad), yielded net lead fluorescence signals ranging from one to seven times the standard deviation of background.

Humans↗

Increased neutron penetration in partially deuterated water: application to neutron capture therapy.

Theoretically, partial deuteration of body water should allow significantly increased neutron penetration in tissue. To evaluate the possible usefulness of partially deuterated water in neutron capture therapy (NCT), neutron flux density distributions were measured in a 23 x 16.5 cm (length x diameter) cylinder for incident thermal and epithermal neutron beams, at 20 and 40 at. % deuteration of water. Relative to neutron flux densities in nondeuterated water, flux densities increased significantly with increasing depth and increasing levels of deuteration. For example, at a depth of 6 cm, flux density was increased approximately 20% to 50% for 20 to 40 at. % deuteration. In a clinical situation, this would increase tumor dose by approximately 30%. Further benefits include the reduced hydrogen neutron capture and the chemical radioprotective effects of partial deuteration for photon radiation.

Body Water↗

In vivo measurement of cortical bone lead using polarized x rays.

An x-ray fluorescence system which utilizes polarized radiation to measure lead in vivo in human subjects is described. The minimum detection limit is approximately 6.4 ppm wet weight lead in the cortex of the tibia with 4 mm of overlying soft tissue. This appears to be adequate for assessing lead stores in lead-toxic preschool children. The measurement requires 16.5 min and is associated with an effective equivalent whole body dose to the subject of 2.5 muSv. The system, its calibration and its validation are described herein.

Bone and Bones↗

Microbeam radiation therapy.

It is proposed to carry out radiotherapy and radiosurgery for brain lesions by crossfiring an array of parallel, closely spaced microbeams of synchrotron-generated x rays several times through an isocentric target, each microbeam in the array having an approximately 25-microns-wide adjustable-height rectangular cross section. The following inferences from the known tissue sparing of 22-MeV deuteron microbeams in the mouse brain and the following exemplary Monte Carlo computations indicate that endothelial cells in the brain that are lethally irradiated by any microbeam in an array of adequately spaced microbeams outside an isocentric target will be replaced by endothelial cells regenerated from microscopically contiguous, minimally irradiated endothelium in intermicrobeam segments of brain vasculature. Endothelial regeneration will prevent necrosis of the nontargeted parenchymal tissue. However, neoplastic and/or nonneoplastic targeted tissues at the isocenter will be so severely depleted of potentially mitotic endothelial and parenchymal cells by multiple overlapping microbeams that necrosis will ensue. The Monte Carlo computations simulate microbeam irradiations of a 16-cm diameter, 16-cm-long cylindrical human head phantom using 50-, 100-, and 150-keV monochromatic x rays.

Brain Neoplasms↗