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Biomedical subjects

R Foster

Publications and source records attributed to R Foster.

At least 109 records · Page 6Linked to original sources

Structure, organization, and regulation of human metallothionein IF gene: differential and cell-type-specific expression in response to heavy metals and glucocorticoids.

We describe a human genomic clone containing the metallothionein (MT) IF and MT IG genes. Southern blot analysis and partial DNA sequence determinations show that these genes are organized in a head-to-head fashion and are located approximately 7.0 kilobases apart from each other. Sequence analysis shows that the MT IF gene contains three exons separated by two introns. All of the intron-exon junctions are defined by the GT-AG rule. The 5' flanking region shows the presence of a duplicated metal regulatory element (TGCGC CCGGCCC) important in heavy-metal induction of this gene and a sequence for its basal level expression (GCGGGGCGGGTGCAAAG). The 5' flanking region is also highly G + C rich (approximately 75%) and contains several GC boxes (GGGCGG), probably important in the binding of transcription factors. The TATAA box and the AATAAA sequence are represented by their variants, the TATCAA box and the AATTAA sequence, respectively. This gene is functional and inducible by heavy metals but not by dexamethasone in mouse LMTK- cells after its transfer on a plasmid containing the herpes simplex virus thymidine kinase gene. Further studies on various human cell lines show that this gene is not expressed in a splenic lymphoblastoid cell line (WI-L2) but is expressed in two hepatoma cell lines (Hep 3B2 and Hep G2) in response to cadmium, zinc, and copper. Dexamethasone appears to have no significant effect on its expression. The studies suggest that the MT IF gene shows cell-type-specific expression and is differentially regulated by heavy metals and glucocorticoids.

Amino Acid Sequence↗

Evaluation of radioimmunoassay performance for staphylococcal enterotoxin in foods: application of external quality assessment survey.

An external quality assessment survey for staphylococcal enterotoxin A, B, and C2 determinations was performed in the collaborative study. Three analysts in two laboratories took part. Three types of food, cheese, salami, and pasta, were artificially contaminated with either one toxin only or all three toxins. A total of 378 analyses were performed. The group mean of the analytical values corresponded fairly well to the given enterotoxin concentrations. However, a considerable interlaboratory imprecision was found despite analyses being performed with the same reagents and methodology.

Cheese↗

Renal transplantation in diabetes mellitus. Influence of preexisting vascular disease on outcome.

We reviewed the recommendations and outcomes for all patients with diabetes mellitus and end-stage renal disease referred to the Medical Center Hospital of Vermont from 1971 through December 1983. During this period, we recommended transplantation in 53 of 73 patients evaluated. Thirty-two transplants were performed in 30 patients. Of the 30 patients, 10 had clinical vascular disease prior to transplantation, i.e., claudication, amputation, active angina, myocardial infarction, or stroke. Seven of the 10 had only claudication or amputation. These 10 patients showed a clear excess in graft failure and mortality. One- and 2-year graft survival was 37 and 13%; patient survival was 48 and 24%. By comparison, the 20 patients without evident vascular disease had 1- and 2-year graft survival rates of 83 and 75% and patient survival rates of 85% at both 1 and 2 years. The incidence of cardiovascular death in the group with vascular disease was 45% at 1 year and 63% at 2 years, as compared with none in the group without vascular disease. The high graft loss and mortality in this group after transplantation should be a major consideration when therapeutic alternatives are considered in diabetics with end-stage renal disease.

Adult↗

Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation.

In 1971 we began a randomized trial to compare alternative local and regional treatments of breast cancer, all of which employ breast removal. Life-table estimates were obtained for 1665 women enrolled in the study for a mean of 126 months. There were no significant differences among three groups of patients with clinically negative axillary nodes, with respect to disease-free survival, distant-disease--free survival, or overall survival (about 57 per cent) at 10 years. The patients were treated by radical mastectomy, total ("simple") mastectomy without axillary dissection but with regional irradiation, or total mastectomy without irradiation plus axillary dissection only if nodes were subsequently positive. Similarly, no differences were observed between patients with clinically positive nodes treated by radical mastectomy or by total mastectomy without axillary dissection but with regional irradiation. Survival at 10 years was about 38 per cent in both groups. Our findings indicate that the location of a breast tumor does not influence the prognosis and that irradiation of internal mammary nodes in patients with inner-quadrant lesions does not improve survival. The data also demonstrate that the results obtained at five years accurately predict the outcome at 10 years. We conclude that the variations of local and regional treatment used in this study are not important in determining survival of patients with breast cancer.

Breast Neoplasms↗

Reversible, cell-heritable changes during the development of tobacco pith tissues.

Cytokinin requiring cells of Nicotiana tabacum L. cv "Havana 425" can be induced in culture to become cytokinin autotrophic. This process is known as cytokinin habituation. Earlier we showed that pith parenchyma tissue consists of inducible cells, which habituate at high rates when treated with cytokinin, and noninducible cells, which remain cytokinin requiring under these conditions. The inducible and noninducible phenotypes are determined states that arise during the development of the tobacco plant and are inherited by individual cells. Here we show that pith tissue of plants regenerated from cloned lines of noninducible cells exhibits the inducible phenotype indicating that noninducible cells, or their descendants, can become inducible. This change in competence for habituation appears to have an epigenetic basis; it is reversible, occurs at high rates, and depends on the developmental state of the cells. The habituated state occurs in two forms that can be distinguished by their difference in developmental potential. Habituated cells derived from inducible pith cells give rise to normal plants whose leaf and pith tissues require cytokinin for growth in culture. In contrast, habituated cells obtained by transferring noninducible cells on media with progressively lower cytokinin concentrations give rise to plants whose leaf and pith tissues exhibit a cytokinin-habituated phenotype in culture.

Cell Line↗

Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update.

The current findings completely affirm the validity of our original observations indicating the appropriateness of grouping primary breast cancer patients into those with negative, 1 to 3, or greater than or equal to 4 positive nodes. Results, however, reveal that there is a risk in combining all patients with greater than or equal to 4 positive nodes into a single group. Since there was a 25% greater disease-free survival and an 18% greater survival in those with 4 to 6 than in those with greater than or equal to 13 positive axillary nodes, such a unification may provide misleading information regarding patient prognosis, as well as the worth of a therapeutic regimen when compared with another from a putatively similar patient population. Of particular interest were findings relating the conditional probability, i.e., the hazard rate, of a treatment failure or death each year during the 5-year period following operation to nodal involvement with tumor. Whereas the hazard rate for those with negative, or 1 to 3 positive nodes, was relatively low and constant, in those with greater than or equal to 4 positive nodes the risk in the early years was much greater, but by the fifth year it was similar to that occurring when 1-3 nodes were involved, and not much different from negative node patients. The same pattern existed whether 4 to 6 or greater than or equal to 13 nodes were positive. When the current findings are considered relative to other factors with predictive import, it is concluded that nodal status still remains the primary prognostic discriminant.

Axilla↗

Angiotensin-mediated calcium efflux from adrenal glomerulosa cells.

The effects of angiotensin II on efflux of radiocalcium and production of aldosterone from dispersed bovine adrenal glomerulosa cells were studied using a flow-through system. Concentrations of angiotensin II between 1.25 X 10(-10) and 1.25 X 10(-8) M were found to stimulate both radiocalcium efflux and the rate of aldosterone production. The increase in radiocalcium efflux occurred within 1.5-2.5 min after angiotensin addition, reached a peak in 3.0-4.5 min, and then declined to a value slightly greater than control. The initial increase in aldosterone production occurred 3-5 min after the peak of calcium efflux. In cells preloaded with [45Ca] and then perfused for 1 h with a medium containing no calcium, the basal rate of aldosterone production fell to zero. Angiotensin II (1.25 X 10(-8) M) caused no increase in aldosterone secretion rate but still caused an efflux of radiocalcium. Exposure of cells to 5 X 10(-5) M verapamil blocked the effect of 1.25 X 10(-10) M angiotensin on both radiocalcium efflux and aldosterone production, but only partially blocked the effects of 1.25 X 10(-8) M angiotensin. In addition to stimulating calcium uptake into adrenal glomerulosa cells, angiotensin II stimulates the mobilization of calcium from an intracellular pool. The precise location of this pool is not known.

Adrenal Glands↗

Ventilatory patterns during steady state and progressive exercise.

This study was conducted to differentiate the ventilatory and metabolic response to supine exercise at low levels (VO2 less than 1000 ml/min) from the well-documented response to high level upright exercise. Further, the respiratory cycle during exercise is analysed in terms of inspiratory time, flow and expiratory time as well as tidal volume and frequency. Using a canopy system for non-invasive measurement of breathing patterns and gas exchange, nine male subjects were studied while performing steady state (SSE) and progressive exercise (PRE). Work loads were: SSE 1-5 Kgm/sec for 17 min; PRE 1.5, 2.5, 3.75 and 5.0 Kgm/sec with 2 min increments. Total work was the same (1548 Kg . m) in both types of exercise. With SSE tidal volume (Vt) and respiratory rate (integral of) rose 70% and 30%, respectively. Minute ventilation (Ve) rose 113%. With PRE, integral of rose during the first work level, then remained stable, while Vt and Ve rose with each incremental exercise level. In both cases a decrease in expiratory time accounted for the major component of the decrease in total cycle time. With the onset of exercise, the rate of increase of inspiratory time and respiratory frequency exceeded that of tidal volume and inspiratory flow. This would suggest that these two groups of parameters are controlled by separate mechanisms, possibly, timing being under neurogenic control and flow determined by humoral factors. The respiratory quotient decreased with both forms of exercise and remained low throughout the exercise period.

Adult↗

Calcium: its role in the mechanism of action of angiotensin II and potassium in aldosterone production.

The role of calcium in the angiotensin II- or potassium-mediated increase in aldosterone production was analyzed in isolated glomerulosa cells prepared from bovine adrenal glands. The response to potassium was highly dependent on the extracellular calcium concentration, and a maximal response was observed at 0.5 mM calcium. The response to angiotensin II was also a function of the calcium concentration between 0 and 0.5 mM Ca but was independent of calcium concentration above this value. The divalent ionophore A23187 also increased aldosterone production in a calcium-dependent manner. Methoxyverapamil blocked the stimulation of steroidogenesis due to angiotensin II and potassium. Calcium fluxes were studied during angiotensin II and potassium stimulation of aldosterone production. Incubation of zona glomerulosa cells with either angiotensin II or potassium at a concentration for maximal stimulation in the presence of radioactive calcium showed a significant increase in calcium uptake. Angiotensin II at a concentration for maximal stimulation increased the calcium uptake measured, using two techniques. Methoxyverapamil inhibited the angiotensin-mediated increase in calcium uptake without affecting the basal rate of calcium uptake. It is concluded that angiotensin II and potassium activate the cells of the glomerulosa by increasing the entry of calcium into the cell, which serves an important messenger function in the response of this cell to angiotensin II and potassium.

Adrenal Glands↗

Patterns of ventilation in postoperative and acutely ill patients.

Acutely ill patients commonly increase minute ventilation (V) to varying degrees. The pattern of breathing utilized to increase V was analyzed in normal subjects and acutely ill surgical patients. V = tidal volume (VT) x frequency (f), or V = inspiratory flow x (TI/TTOT, inspiratory time/total cycle time). CO2 inhalation and exercise were used to induce supine hyperventilation in normal subjects. This was compared to hyperventilation in acutely ill surgical patients. Measurements were made of O2 consumption, CO2 production, V, VT, f, inspiratory flow, TI, and TTOT. With small increases in V (up to twice control), normal subjects increased inspiratory flow and TI/TTOT with both CO2 and exercise. CO2 inhalation increased VT with no change in f, while exercise increased both VT and f. When V increased beyond twice control, TI/TTOT remained constant and increases in inspiratory flow accounted for the entire increase in V. In acutely ill patients with increased V, average f was elevated and VT decreased, but there was no constant relationship of f and VT with increasing V. However, TI/TTOT was relatively constant at 0.40- 0.46; therefore, in order to increase V, inspiratory flow had to increase! Patients also showed a tendency to breathe at a relatively fixed VT while normal subjects did not show this phenomenon, even with increases of up to 3 times control V. Continuous, rapid analysis of gas exchange and breathing patterns holds promise for early detection of patients with V inappropriate to metabolic demands, and serves as a sensitive indicator of abnormal patterns used by acutely ill patients to increase V.

Acute Disease↗