Hair trace elementary profiles in aging rodents and primates: links to altered cell homeodynamics and disease

Aging is associated with an increased incidence of pathological conditions such as neurodegeneration, cardiovascular and renal disease, and cancer. These conditions are believed to be linked to a disruption in cell homeodynamics, which is regulated by essential trace elements. In this study we used hair elementary analysis by inductively coupled plasma mass spectrometry (ICPMS) to examine age-related profiles of 47 elements in both rats and common marmoset monkeys. Hair was collected from young adult (6 months) and aged (18 months) Long–Evans male rats, and young adult (2 years), middle-aged (4 years) and aged (>8 years) marmosets. The results revealed that aging reduces content levels of cobalt, potassium and selenium while content levels of aluminium, arsenic, boron, mercury, molybdenum, and titanium were elevated in aged rats. Similarly, aged marmosets showed reduced levels of cobalt and elevated levels of aluminium. Case studies in aged rats revealed that myocardial infarction was associated with elevated levels of sodium, potassium and cadmium and reduced zinc, while renal failure was linked to elevated content of potassium, chloride and boron and reduced contents of manganese. Carcinoma was linked to elevated arsenic and reduced selenium levels. These findings indicate that hair elementary profiles in healthy aging and age-related diseases reflect altered cell and organ metabolic functions. Cobalt and aluminium in particular may serve as biomarkers of aging in animal models. Thus, elementary deposition in hair may have predictive and diagnostic value in age-related pathological conditions, including cardiovascular and kidney disease and cancer.     

Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony- forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.     

Physiological and thermal responses of males with varying body compositions during immersion in moderately cold water.

The effect of body composition on the thermal and metabolic responses of 24 male volunteers (20 to 35 years) was examined during 90 min of moderately cold (18, 22, or 26 degrees C) water immersion to the first thoracic vertebrae. Body composition was determined via underwater densitometry. Subjects were divided with respect to body fat (high fat (HF) = 18-22%, n = 12; Low fat (LF) = 8-12%, n = 12) and randomly assigned to one of three water temperatures. Rectal temperature (degree C) after 90 min of immersion did not differ in LF and HF at 18 degrees C (35.9 vs. 36.2), 22 degrees C (36.0 vs. 36.0), and 26 degrees C (36.0 vs. 36.3). Oxygen uptake (VO2, ml-kg-1.min-1) was greater in LF than in HF in all water temperatures. Oxygen uptake at 90 min was greater for LF than HF in 18 degrees C (11.48 vs. 9.19), 22 degrees C (9.79 vs. 4.70), and 26 degrees C (6.21 vs. 5.44). Mean skin temperature in LF and HF approached water temperature within the first 5 min. Despite the thermal strain of cold water immersion, the LF subjects were able to maintain a similar Tre compared to the HF due to a significantly greater shivering thermogenesis.     

Recovery of T cell subsets after autologous bone marrow transplantation is mainly due to proliferation of mature T cells in the graft

In 22 patients with malignancies, treated with high-dose chemoradiotherapy and autologous bone marrow transplantation (BMT), peripheral blood T cell subsets and functions were studied. In ten cytomegalovirus (CMV)-negative patients, CD4+ and CD8+ T cells (representing T cells of the helper/inducer phenotype and T cells of the suppressor/cytotoxic phenotype, respectively), recovered slowly and simultaneously. In 12 CMV-positive patients, however, CD8+ T cells recovered more rapidly than CD4+ T cells and rose to increased counts. No T cells with an immature phenotype (CD1+, OKT6+) were observed. Lymphocyte stimulation by herpes simplex virus infected fibroblasts (and by CMV-infected fibroblasts in CMV-positive patients) in contrast remained high and even increased after BMT in both groups. These data indicate that T cell recovery after autologous BMT is mainly due to proliferation of mature T cells present in the BM graft and not to generation of new T cells from T cell precursors.     

Classification of left ventricular thrombi by their history of systemic embolization using pattern recognition of two-dimensional echocardiograms

Although one can diagnose left ventricular (LV) thrombi by two-dimensional echocardiography (2DE), the factors associated with peripheral embolization, given a 2DE with LV thrombi, have not been well delineated. Therefore we looked at 2DE and clinical variables that included texture features in the 2DE of 38 patients whose 2DE had LV thrombi and questioned these patients to see if clinical embolization had occurred in the 8.9 +/- 6.1 month (+/- SD) average follow-up period. Eight patients, four with acute myocardial infarction (AMI) and four with dilated LV and decreased LV systolic wall motion, had clinically apparent leg or brain emboli, whereas the remaining patients did not. Emboli occurred within a week of obtaining the 2DE in question. The variables considered were the age of the patient, the type of heart disease present, warfarin administration, exercise tolerance, standard M-mode measurements, LV dyssynergy by 2DE, clot size and mobility, and gray scale statistics which include run length, Sobel edge points followed by 50% gradient thresholding, gray level second-order statistics, offset 1 and gray level difference statistics, offset 1. The values of the variables were then entered into an expert system (Expert Ease) in order to achieve classification of patients into emboli versus no emboli groups, while using a minimal number of variables. The only variables that were needed included run length, long runs emphasis, gray level difference statistics (entropy, contrast, mean, and angular second moment), gray level second-order statistics (contrast), and warfarin status. When probability statistics were applied to this schema, its accuracy was predicted to be at least 96%.(ABSTRACT TRUNCATED AT 250 WORDS)