Cytostatic and cytolytic effects of human recombinant tumor necrosis factor on human renal cell carcinoma cell lines derived from a single surgical specimen

The purpose of this study was to determine whether human tumor cell lines derived from a single tumor exhibit heterogeneous responses to the anti-tumor effects of human recombinant tumor necrosis factor (h-r-TNF). Several cell lines with different metastatic propensities have been established in culture from a single surgical specimen of a human renal cell carcinoma following different selection procedures in nude mice. The cell lines exhibited significant differences in in vitro susceptibilities to cytotoxic effects of TNF. Kinetic analysis of the interaction of TNF with susceptible renal carcinoma cells demonstrated that a short 30 min interaction of TNF with the cells is sufficient to produce significant lysis 72 hr later. One cycle of exposure of sensitive cells to h-r-TNF did not produce cells resistant to it, nor did the degree of sensitivity to h-r-TNF vary after one passage of the cells in nude mice. Tumor cell resistance to the effects of TNF did develop spontaneously after prolonged cultivation in culture. We conclude that tumor cells derived from a single human renal cell carcinoma exhibit a heterogeneous response to the cytotoxic effects of h-r-TNF.     

Antigenicity of UV radiation-induced murine tumors correlates positively with the level of adenosine deaminase activity

Summary The specific activities of adenosine deaminase (ADA) in 16 murine tumor cell lines derived from seven UV light-induced neoplasms (melanoma and fibrosarcoma) were determined. In each case, the specific activity of ADA correlated positively with the antigenicity of the tumor cells. Highly antigenic cell lines that regress upon introduction into syngeneic hosts had on average 4- to 6-fold higher ADA specific activities than cell lines of low antigenicity that grow progressively in syngeneic hosts. The antigenic differences are probably not related to intracellular cAMP levels, as the level of cAMP differed only 2-fold between the two groups of cell lines.     

Prophylactic Internal Fixation of Secondary Neoplastic Deposits in Long Bones

The notes and radiographs of 19 patients who had pathological fractures of long bones due to secondary neoplastic deposits were reviewed. Involvement of over half of the cortex is recommended as an indication for prophylactic internal fixation to prevent the development of a pathological fracture. Eight patients were treated successfully in this way. A notable secondary effect of prophylactic internal fixation was the considerable reduction in pain at the site of the lesion.     

The Mantel-Haenszel Procedure Revisited: Models and Generalizations

Several statistical methods have been developed for adjusting the Odds Ratio of the relation between two dichotomous variables X and Y for some confounders Z. With the exception of the Mantel-Haenszel method, commonly used methods, notably binary logistic regression, are not symmetrical in X and Y. The classical Mantel-Haenszel method however only works for confounders with a limited number of discrete strata, which limits its utility, and appears to have no basis in statistical models. Here we revisit the Mantel-Haenszel method and propose an extension to continuous and vector valued Z. The idea is to replace the observed cell entries in strata of the Mantel-Haenszel procedure by subject specific classification probabilities for the four possible values of (X,Y) predicted by a suitable statistical model. For situations where X and Y can be treated symmetrically we propose and explore the multinomial logistic model. Under the homogeneity hypothesis, which states that the odds ratio does not depend on Z, the logarithm of the odds ratio estimator can be expressed as a simple linear combination of three parameters of this model. Methods for testing the homogeneity hypothesis are proposed. The relationship between this method and binary logistic regression is explored. A numerical example using survey data is presented.     

Perfusion fixation of the newborn opossum: equipment and techniques.

A 30-gauge cannula was used to perfuse fixative through the fragile heart of a newborn opossum. The cannula was gently maneuvered into the heart and held in place with a specially designed manipulator. The flow rate of the fixative was regulated with an infusion set connected to the cannula.     

Perceived Stress and Weight Gain in Adolescence: A Longitudinal Analysis

Although perceived stress has been hypothesized to be a risk factor for obesity, epidemiological studies relating stress to weight gain have shown mixed results. We examined prospective associations between perceived stress and changes in waist circumference and BMI in a large study of adolescents. As part of the Health and Behaviour in Teenagers Study (HABITS), height, weight, and waist circumference were measured annually in 4,065 adolescents aged from 11 to 16. Waist and BMI standard deviation scores (SDS) were used as indices of adiposity. Adolescents completed a measure of perceived stress each year, from which mean stress scores over the 5‐year period were also calculated and divided by tertile into lower, moderate, and higher stress. Associations between perceived stress at each year and adiposity 1–4 years later and also adiposity trajectories over the whole period in relation to mean stress were investigated. Analyses were adjusted for age, sex, ethnicity, socioeconomic deprivation, pubertal timing, and smoking. Perceived stress in any year was not related prospectively to increases in waist or BMI SDS 1–4 years later, nor was there any evidence that higher stress over the whole period was associated with greater gains in waist or BMI SDS. However, waist and BMI SDS were significantly higher in the moderate‐ and higher‐stress groups than the lower‐stress group across the whole 5‐year period. Persistent stress was associated with higher waist circumference and BMI in adolescence, but did not lead to differential changes over 5 years.     

Gene expression of the tyrosine kinase receptor c-kit during ovarian development in the brushtail possum (Trichosurus vulpecula).

Ovarian development and function have been extensively studied in eutherian species, with stem cell factor and its receptor, c-kit, having been shown to play key roles at various stages of these processes. In contrast, relatively little is known regarding ovarian development in marsupials. The aims of this study were, first, to establish the timing of key events during germ cell maturation and follicular development and, second, to determine the timing and cellular localization of gene expression for c-kit in the ovaries of a marsupial, the brushtail possum (Trichosurus vulpecula). For this study, ovaries were collected from possums ranging in age from Day 1 after birth to adult. Using stereology, the number of germ cells was found to increase rapidly during the first 60-100 days of life. This was followed by a sharp decline in number, wherein almost 90% of germ cells had disappeared by Day 180. From histological examinations, the time of initiation of meiosis, follicular formation, and follicular growth were determined to occur on Days 35, 50, and 60, respectively. Using in situ hybridization, c-kit gene expression was localized to germ cells and somatic cells during the first 15 days of life; however, after Day 30 and into adult life, c-kit expression was exclusive to germ cells. Results from this study suggest that the pattern of ovarian development is similar in marsupials to eutherians, and that c-kit may play a key role in germ cell development at various stages throughout life.