William R. Jewell

Immediate effect of irradiation on microvasculature

The immediate effects of irradiation on microvasculature in muscle in an animal model are described in this paper. By using triple isotopes of 125I, 131I, and 22Na, the transcapillary transfer of albumin from the vascular bed to the extravascular space is determined in terms of mg/g of tissue, after single doses of 2 to 14 Gy. These results reveal an increase in the extravascular albumin immediately after irradiation and suggest an instantaneous compromise in vascular permeability even after 2 Gy. This effect was apparently dose related.

Study of function and maturation of monocytes in morbidly obese individuals

In recent years there has been an intense interest in understanding the mechanisms involved in immune modulation associated with dietary restriction. In this study we have investigated maturation of peripheral blood monocytes in morbidly obese patients using an in vitro culture system. At the end of the culture, the matured monocytes (macrophages) were quantitated. Though there was no detectable functional defect observed in the matured monocytes in vitro, there was a quantitative difference in maturation among the monocytes plated. The number of monocytes that matured into macrophages in obese patients was 3.29 ± 2.41 × 104 cells per milliliter of blood, as compared to 8.24 ± 3.14 × 104 per milliliter of blood in normal volunteers. This difference was found to be statistically significant at P < 0.001. These results indicate a possible development of an intrinsic defect among morbidly obese individuals.

Characterization of Fc receptors associated with breast carcinoma

Abstract Seventeen specimens of histologically confirmed breast carcinoma were evaluated by a closed-chamber hemadsorption technique and rosette formation in single-cell suspensions for the presence of Fc receptors. Sheep erythrocytes sensitized by various amounts of rabbit anti-sheep erythrocyte antibodies were used as indicator cells. The binding specificity for indicator cells to tissue sections was analyzed by inhibition experiments using pooled human IgG, rabbit IgG, IgG(Fab) 2 , IgG(Fc), IgG(Facb), aggregated IgG, Ag-Ab complexes, and human serum albumin. These studies suggest that the detection of Fc receptors is dependent on the antibody coating of sheep erythrocytes and suggest that the attachment of indicator cells to Fc receptors is specific for the Fc portion of antibody molecules.

Interrelationship between monocyte maturation in vitro and tumor growth in murine tumor host

Abstract A mononuclear cell-rich fraction was isolated from the peripheral blood of normal Sprague-Dawley rats and rats with growing Walker 256 carcinosarcoma. The mononuclear cells were cultured in microtest plates over a period of 7 days. Monocyte maturation was studied, and macrophage precursors were counted periodically as the tumor grew. The number of macrophage precursors diminished as the tumor size became larger. But, when the tumor was excised, the number of macrophage precursors returned to a normal value postoperatively. However, the peripheral blood monocyte counts were not depressed at any time. This observation indicates a monocyte maturation defect in the tumor host.

Quantitative studies of monocyte maturation in patients with malignant melanoma.

Peripheral blood monocytes were cultured from normal volunteers and patients with malignant melanoma in a suspension culture containing 50% autologous plasma. The number of monocytes that matured into macrophages in the normal control population was 8.29 +/- 3.14 X 10(4) cells/ml blood, whereas in patients with malignant melanoma the number of matured monocytes was 3.15 +/- 2.80 X 10(4) cells/ml blood. The low macrophage maturation in patients with malignant melanoma was not found to be associated with any serum factors. Furthermore, from morphological studies done using scanning electron microscopy, there was no apparent difference between macrophages maturing from normal individuals or patients with malignant melanoma. From analysis of this adherent cell population there appears to be an intrinsic defeat in the maturation of monocytes in vitro in the case of patients with malignant melanoma.

Energy kinetics and role of nutrition in cancer patients

Abstract There is an increasing awareness of the interrelationship between cancer and nutrition. Cachexia is a clinical syndrome often seen in terminal cases of cancer. In this study the present concept of energy production and utilization is thoroughly reviewed, and a conceptional theoretical model is developed to represent energy production and utilization in four stages; namely, intake of nutrients, processing of nutrients into macromolecules by digestion and absorption, metabolism into fuel, and utilization of fuel by cells to carry out essential life processes. Next, the model is extended to the pathological state of cancer. A mathematical model depicting theoretical data available and the clinical presentation in a cancer patient is developed. Applying real values to various constants, the mathematical model is analyzed in the computer IBM 360 to obtain the energy available and energy depleted in cancer hosts. The analysis vividly represents the clinical state of patients with cancer from the occurrence of a small tumor to cachexia, and ultimately to death. The analysis helps in understanding the process of development of cachexia and the logic behind advocating nutritional therapy as adjuvant to major therapy, such as radiation therapy, surgery, and chemotherapy, for successful treatment of cancer.