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Biomedical subjects

A E Schaefer

Publications and source records attributed to A E Schaefer.

At least 19 recordsLinked to original sources

Uptake of cadmium is diminished in transfected mouse NIH/3T3 cells enriched for metallothionein.

To determine the relationship between cellular uptake of cadmium and content of metallothionein, we measured uptake of 109Cd in cells that differed in content of metallothionein (MT). MT cells were derived from NIH/3T3 cells by transfection with a plasmid containing the genome of bovine papilloma virus and the mouse metallothionein-I gene, driven by the promotor for the glucose-regulated protein of 78 kDa. Control cells were similarly transfected with bovine papilloma virus-based plasmids with the gene for metallothionein inverted and thus separated from the promoter (TM), or deleted, along with the promoter (BPA). The number of copies of bovine papilloma virus-based plasmids was similar in MT, TM, and BPA cells, approximately 100 per cell. MT cells were more than 10 times more resistant to the lethal effect of cadmium than were the control cells. Synthesis of metallothionein was 15-fold greater in the MT cells than in the TM or BPA cells. The uptake of 109Cd by the cells enriched in metallothionein was 4-fold less than by the control cells. These data suggest that an increased content of metallothionein may protect some cells from the toxic effects of cadmium, in part, by diminishing uptake of the metal.

3T3 Cells

Successful immunotherapy of mouse melanoma and sarcoma with recombinant interleukin-2 and cyclophosphamide.

Recombinant human interleukin-2 (rIL-2, courtesy of Cetus Corporation, Emeryville, CA, U.S.A.) is highly effective in eradicating syngeneic tumor when administered to C57BL/6 mice implanted with a nonimmunogenic, rapidly growing clone of B16 melanoma, or an immunogenic methylcholanthrene-induced sarcoma, 1-3 days, before beginning treatment at 5 X 10(4) U/injection daily for 5 days, and then on alternate days for 4 weeks. Low-dose cyclophosphamide (CY, 50 mg/kg), injected intraperitoneally (i.p.) 4 times at weekly intervals, greatly facilitated tumor eradication in rIL-2-treated mice. Most early subcutaneous (s.c.) tumors were cured by combining CY i.p. with repeated perilesional s.c. injections of rIL-2, i.e, 100% cure for 1-day and 87-91% for 3-day melanomas. When rIL-2 was administered without CY, the cure rate was 64% for 1-day and 67% for 3-day melanomas. This cure rate indicated a synergism between rIL-2 and CY, since CY alone did not affect tumor incidence. CY was therefore administered in all subsequent experiments. Treatment with rIL-2, localized to the site of the melanoma or sarcoma, was most effective, although systemic (i.p.) administration achieved results regardless of tumor site. When either tumor was implanted s.c. and rIL-2 treatment was also given s.c. locally, beginning 1-3 days later, 87-100% of the mice were cured, compared with 35-50% cured when rIL-2 was administered i.p., and 0% cured in excipient buffer-injected controls. Conversely, with i.p. treatment of i.p. tumors, 60-83% of the mice were tumor-free on day 50, as compared with only 17% tumor-free if treatment was s.c. These in vivo model systems should prove useful in helping establish protocols for human therapy.

Animals

Strong suppression by monocytes of T cell mitogenesis in chicken peripheral blood leukocytes.

Peripheral blood leukocytes (PBL) isolated from chicken blood by flotation on Ficoll-Hypaque (FH) have much lower proliferative responses to Con A and PHA than PBL isolated by slow-speed (SS) centrifuging at 60 X G. FH preparations contain all categories of blood cells except erythrocytes, whereas SS are almost devoid of nonlymphoid cells. FH responses approach SS levels after filtration through Sephadex G-10, which removes almost all monocytes detectable by neutral red and nonspecific esterase methods, while only partially depleting granulocytes and thrombocytes. Thus, the low responses of FH are probably associated with suppressor activity of monocytes in these preparations, numbering 6 to 8% of mononuclear cells. G-10 filtration decreases responses of SS preparations, indicating that the few (less than 0.1%) monocytes in SS function mainly as helper cells. In co-cultures, irradiated FH cells (FHX) but not SSX produce as much as 90% suppression of SS or FH responses. Suppression by FHX is totally inhibited by heat killing (56 degrees C for 45 min) or monocyte inactivation by preincubation with Trypan blue, and is removed by G-10 filtration, although not completely. Adherent cells isolated from unirradiated FH on Cytodex beads (ADC-CY) produce up to 99% suppression in co-culture with SS or nonadherent cells derived from FH. Soluble suppressor factors can be detected in conditioned media from supernatants of Con A-stimulated cocultures containing suppressor monocytes, but their suppressor activity is partially opposed by stimulatory factors, possibly interleukin 2, also present in supernatants. It is concluded that in FH preparations and therefore in blood, but not in SS, monocytes that have not been activated exert strong suppressor activity on mitogen-induced T cell proliferation. Occasional chickens of one inbred line, RPRL 72, had exceptionally high suppressor activity of monocytes, as shown by very low FH responses and very high suppressor effects of FHX well outside the normal range of variation found in this line or in line RPRL 63. This abnormal suppressor activity may have resulted from activation of suppressor monocytes as a response to subclinical infection.

Animals

Nutritional status of an institutionalized aged population.

The nutritional status of 146 elderly residents in a long-term care facility was evaluated using biochemical and anthropometric measures. The level of nursing care required and meal locale had no significant effect on the overall nutritional status of the residents. The biochemical data indicated three nutritional problems requiring treatment and follow-up: anemia, low vitamin B6 status, and reduced albumin levels. The incidence of these problems in other groups of elderly deserves further study. Six percent of the study population were anemic, with 13% having low serum folate, 6% with low transferrin saturation, and 31% with low TIBC values suggesting more than one factor involved in the anemia. Low vitamin B6 status was observed in 28% of the population. Whether this is due to poor intake, poor absorption, or both is not known. The percentage of residents with decreased albumin levels was slightly higher than that observed in other studies of the elderly, and may be related to the more advanced age of this population.

Aged

Food eating patterns and health: a reexamination of the Ten-State and HANES I surveys.

Dietary, clinical, and biochemical data from the Ten-State Nutrition Survey (1968 to 1970) and the Health and Nutrition Examination Survey I (1971 to 1974), have been reexamined by factor analysis to focus attention on eating patterns as a means of relating food intake to health. The seven statistically different eating patterns generated were characterized by disproportionate consumption of different food groups. The relationship between the combination of foods that people ate and the state of their nutritional health was examined for both samples in total, and for various age, sex, race, region, and income groups within the Health and Nutrition Examination Survey I sample. Significantly different associations between the seven eating patterns and the absence of clinical symptoms and biochemical deficiencies were found. Some eating patterns consistently stood out as being significantly better or worse in this regard (p less than 0.05). This food eating pattern model should prove useful for 1) examining the association between food consumption and the incidence of disease states, such as obesity, hypertension, cardiovascular disease, cancer, and periodontal disease for various large scale dietary-health surveys, 2) establishing food regulatory policies, 3) setting national dietary goals, and 4) educating the public on nutrition and health issues.

Adolescent

Nutritional status of elderly participants in a congregate meals program.

This study was conducted to determine the nutritional status of elderly subjects participating in a congregate meals program. Twenty-four-hour recalls, anthropometric measurements, and biochemical determinations were the criteria used to determine nutritional status of the 30 volunteers. Information regarding use of dietary supplements was also obtained. Ninety-three percent of the participants consumed diets providing at least 70 percent of the RDA for the 13 nutrients calculated. Seven percent consumed diets rated as "poor," but none of the participants consumed diets supplying less than 54 percent of the RDA. Twenty-seven percent of the sample reported daily use of dietary supplements. Height, weight, mid-arm circumference, triceps skinfold, and abdominal circumference were measured. The incidence of obesity was high, with 42 percent of the women and 78 percent of the men being over 119 percent of ideal body weight. Mid-arm circumference, triceps skinfold, and abdominal circumference data agreed with the weight-for-height data. The incidence of obesity was greater in this study than in other studies cited, and, as was not the case in other studies, the incidence of obesity was greater in men. Biochemical determinations included hemoglobin, hematocrit, serum albumin, serum folate, ascorbic acid, and vitamins A, B6, and B12. Comparison of biochemical data with accepted standards indicated that the nutritional status of the participants was adequate.

Age Factors

Nutritional needs of special populations at risk.

The nutritional needs of special populations at risk require a concerned government, a concerned bureaucracy which funds and operates health, welfare and food delivery systems. Equally, if not even more important, is the concern and involvement of citizens at the "local-state-county-city" level. Some of the vulnerable groups, such as the migrant workers and the Native Americans, are the responsibiliity of the Federal Government. This does not mean that State and local citizens should do nothing, which by and large characterizes what has happened. The solution to provide optimum nutrition for the entire U.S. population is not merely a recitation of: food production figures, food costs, documentation of how much the Government spends on feeding people, how many free or reduced school lunches are served, how good or bad the problem is. We need to update and monitor programs that deal with the delivery of health, welfare and food; nutrition education for educators, Congress, doctors, and the public; food enrichment and fortification; nutrient analysis of foods; and nutrition research.

Adolescent

Studies on tolerance induction in vitro. II. Requirements for the generation and transfer of suppressor cell activity.

The induction of specific immunologic tolerance and its transfer has been studied in the in vitro response of unprimed rabbit spleen cells to solubilized phage antigens. Evidence presented shows that only viable cells transfer tolerance and that the responsible cells appear devoid of membrane-bound antigen but are sensitive to anti-thymocyte serum. It appears, therefore, that although the in vitro response to solubilized S-T2 has no demonstrable requirement for T "helper" cells, it is subject to the action of T "supp "suppressor" cells.

Animals