Moderate exercise training slows mammary tumour growth in adolescent rats.

Adolescence and young adulthood may be critical windows in establishing risk for breast cancer development in humans. Epidemiological data suggest that exercise during this life stage is associated with decreased breast cancer risk yet few experimental studies to elucidate the mechanism have been performed. The purpose of these studies was to evaluate the effects of moderate exercise training on mammary tumour development in adolescent rats using the 1-methyl 1-nitrosourea (MNU) chemical carcinogen model. Exercise (EX) consisted of moderate-intensity treadmill running 30 min/day, 5 days a week. A total of 274 animals were used: 94 in study 1 and 180 in study 2. Animals were injected with MNU (50 and 25 mg/kg body weight in studies 1 and 2, respectively) at 21 days of age and began training at 28 days of age. Groups of animals (n=10-30 depending on the study and time point) were sacrificed every 2 weeks for 8 weeks to evaluate tumour development. No difference in median tumour-free survival time was observed in the EX versus sham-exercise (SHAM), nor were there any differences in multiplicity at either a high or moderate dose of MNU. Latency to first tumour palpated was increased in both studies by 3-4 days. Consistent across both studies, tumour weights were less and the growth rates of the tumours, defined as tumour weight divided by the number of days elapsed since the tumour was first palpated, were reduced in the EX group. The data suggest that latency is increased and tumour growth is retarded in response to moderate exercise training.

Proliferative responses of T cells from the skin and nerve lesions of leprosy patients.

In the current study we compared the mitogenic responses of T cells from skin and nerve biopsies of leprosy patients with those of peripheral blood mononuclear cells (PBMC). Lymphocytes from these sources were cultured at < or = 100 cells/well in the presence of PHA, irradiated autologous feeder cells, and IL-2, and proliferation was assessed after 6 to 12 days. Whereas PBMC were capable of vigorous responses, the growth of cells from skin and nerve was markedly reduced. The diminished response was independent of the clinical status of leprosy patients and was also observed in skin-infiltrating lymphocytes from patients suffering from other disorders. Analysis of proliferative responses at 1 cell/well suggested both a reduction in precursor frequency and a decrease in mean burst size. Analysis of lymphokine production suggested that cultured cells from skin lesions had reduced IL-w and IL-4 production relative to PBMC generated under similar conditions. Equal numbers of CD3+ cells were present in each source, but lesion cells were enriched in CD45RA- "memory" T cells, as well as CD3+CD28+ T cells. However, these alterations in subpopulation distribution could not account for the substantial differences in proliferative potential. We conclude that significant differences exist in the activation potential of cells from different tissue sources.

Cellulose sponge punch for controlled mitomycin application.

We describe a new punch for cellulose sponges that helps to standardize the application of mitomycin during glaucoma filtration surgery. The punch was used to create 40 cellulose application disks. The height, diameter, and weight were measured in both wet and dry states. The disk dimensions and weights were reproducible, with a coefficient of variation less than 5 for all categories. The punch has been very useful in our clinical practice and research.

Factors affecting articular cartilage thickness in osteoarthritis and aging.

OBJECTIVE: To test the hypothesis that both aging and osteoarthritis (OA) contribute to the variance of human articular cartilage thickness of the knee and whether these contributions occur predominantly at weight bearing cartilage sites. METHODS: Thin, sagittal magnetic resonance images (MRI) of both knees were examined in 52 patients with idiopathic OA of the knee of short duration (87%: < or = 4 years) and 40 reference subjects of comparable age and sex distribution. Articular cartilage thickness was measured at the weight bearing and nonweight bearing femoral condylar, tibial plateau, and posterior patellar sites. Multiple regression analyses were performed to examine the influence of OA, age, sex, obesity (body mass index), and bone size on cartilage thickness. RESULTS: Age accounted for a significant linear decrease (p < 0.001) in both lateral and medial weight bearing femoral cartilage thickness of both knees, but failed to account for any significant variance in thickness at other cartilage sites. OA accounted for a significant decrease (p < 0.02) in the thickness of the femoral articular cartilage in the medial and lateral right knee compartments and in the lateral left knee compartment, but not in the medial left knee compartment. Significant cartilage thinning could be detected by MRI in patients with OA, even when the joint space was normal radiographically. CONCLUSION: The asymmetric decrease in the left knee may reflect the effect of mechanical factors. Our data show that articular cartilage thickness decreases at the femoral weight bearing sites both with age and as a consequence of OA and that these contributions can be distinguished from one another.

Localizing genes that defer senescence in Drosophila melanogaster.

Selection for age-specific reproduction has produced replicate stocks in which life span exceeds that in short-lived controls by about 30 per cent, in unpaired individuals. Crosses between a selected long-lived (L) stock, short-lived (S) stock and a strain with balancer chromosomes were used to create all possible combinations of their chromosomes. The longest and shortest-lived genotypes are found to be (LSL) and (SLS), with other combinations distributed between them approximately according to their first and third chromosomes. Longevity appears to be under polygenic control with contributing elements on all chromosomes. The third chromosome is by far the most influential, accounting for 66 to 72 per cent of the observed variation in females. The first chromosome is less effective. Epistatic interactions are more important in males than females, but are significant only in measurements of single individuals. Some controlling elements for longevity appear to differ in males and females. Crosses of selected stocks with known P and M-cytotype strains show no effect on either sterility or longevity.

Influence of antecedent lymphoid surgery on the odds of acquiring rheumatoid arthritis.

The occurrence of rheumatoid arthritis (RA) and the extent of antecedent lymphoid surgeries was examined using case control study methods. Two hundred sixty-four patients with definite or classic RA were considered and 283 patients with rheumatic diseases presumably of nonimmunologic origin were used as controls. The odds for developing RA were found to be significantly higher for patients with multiple lymphoid surgeries (tonsillectomy and adenoidectomy or tonsillectomy and adenoidectomy plus appendectomy) and exhibited a gradient, increasing with more extensive surgery. Significant rank correlations were found in patients with RA between the age at tonsillectomy and the rheumatoid factor (RF) titer. An earlier tonsillectomy correlated with lower titers of RF. A significant decrease of serum RF titer was also seen in patients with RA subjected to tonsillectomy, adenoidectomy and appendectomy. We conclude that antecedent removal of lymphoid tissue from the tonsils, adenoids and appendix constitutes a risk factor predisposing to RA. Moreover, this risk seems related to the quantity of lymphoid tissue removed.

Aggressiveness of SJL/J lymphomas correlates with absence of H-2Ds antigens.

SJL/J lymphomas emerged as H-2Ds-negative variants upon transplantation of their respective H-2Ds-positive spontaneous tumors. Of nine spontaneous SJL/J lymphomas examined, only two contained detectable numbers of H-2Ds-negative tumor cells. Of seven successfully transplanted tumors, however, four emerged as predominantly H-2Ds-negative tumors by their second transplantation. Long term SJL/J lymphoma lines, RCS 5 and SJL/SJL, were also found to be H-2Ds-negative. The expression of H-2Ks and I-As were maintained on all tumor lines examined. H-2Ds-negative tumor cells were consistent stimulators of syngeneic lymphoproliferation, whereas tumors maintaining H-2Ds expression varied in their stimulatory capacity. Transplantation times required to achieve morbidity in syngeneic mice correlated with tumor cell expression of H-2Ds. Tumors maintaining H-2Ds expression were less aggressive and required 57 to 150 days to produce morbidity compared with highly aggressive H-2Ds-negative tumors that required only 7 to 10 days at one-quarter of the cell dose (10(7) cells). Growth curve analysis based on spleen weights (corrected for body weight) indicated that three types of SJL/J lymphomas could be identified based on their expression of H-2Ds and ability to stimulate syngeneic lymphoproliferation: 1) indolent, nonstimulatory H-2Ds-positive tumors; 2) indolent, stimulatory H-2Ds-positive tumors; and 3) highly aggressive, stimulatory H-2Ds-negative tumors.

Survival of mice receiving melanoma transplants is promoted by hydroquinone.

In BALB/c female mice with melanoma transplants, the incidence of "takes" is decreased and survival is increased by hydroquinone, a melanocytolytic agent. The mechanism of drug action is suggested by via DNA. The significant and high degree of positive response to hydroquinone treatment in vivo is encouraging for the clinical management of melanoma with melanocytolytic agents.

Sample stability: a suggested definition and method of determination.

We propose defining the stability of any chemical constituent of stored samples in terms that are quantitatively related to the precision of the measurement by which it is determined. We suggest that a constituent may be considered stable, for a stated period and under exactly defined conditions, when the average change in its measured value is less than a chosen number, K, of standard deviations of the data obtained by the measuring method over the concentration range in question. Based on this definition a technique utilizing a graphical truncated normal sequential test is presented as the appropriate experimental and statistical design for measuring stability. The statistical basis for the proposal is presented.

Estimation of norms from a controlled sample survey. II. Influence of body habitus, oral contraceptives, and other factors on values for the normal range derived from the SMA 12-60 screening group of tests.

PIP: The Westenberg-Mood 2-sample percentile test was used to determine if ranges of normal values for subgroups varied for variables measured on the SMA 12/60 ("AutoAnalyzer 12/60", analyzes serum). Data on 12 frequently determined serum constituents was collected from people age 20-49. Subjects were clinically normal men (423) and women (557). Individuals were subgrouped according to 1) sex, 2) geographical region of the U.S., 3) body habitus (weight), 4) season of the year when serum was drawn, 5) time of day, and 6) medications, if any, being used. Some of the more striking observations were 1) obese persons had higher concentrations of uric acid, 2) albumin and inorganic phosphate concentrations were decreased in women using oral contraceptives, and 3) lactate dehydrogenase activities were lower in the winter months. A laboratory test has increased usefulness when the normal range is narrowed; analysis of serum constituent levels in subgroups achieves this purpose.^ieng

The effect of optical polarization on reflection spectra.

The theoretical basis for polarization effects in reflection spectra are reviewed. It is shown that light polarized parallel to the plane of incidence interacts more strongly with the absorbing species than does light of perpendicular polarization except under conditions of internal reflection when the absorber is a thin film between two nonabsorbing media. In this instance the relative degree of interaction is determined by the refractive indices of the three phases. Experimental results are presented which show the predicted effects for internal reflection spectroscopy both when the absorbing medium is a solution of (CH(3))(4)NCl in D(2)O and when it is a monolayer of stearic acid.