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Biomedical subjects

N Levin

Publications and source records attributed to N Levin.

At least 91 records · Page 5Linked to original sources

Characterization of corticosterone feedback regulation of ACTH secretion.

Adrenalectomy-induced increases in ACTH secretion in rats are returned to normal by an action of corticosterone on the brain, not on the pituitary. Five days after adrenalectomy with constant steroid replacement, the concentration of free corticosterone in plasma which reduces plasma ACTH by 50% is approximately 0.8 nM. By contrast, the concentration of free plasma corticosterone required for 50% reduction of thymus wet weight or plasma transcortin concentration (both targets for glucocorticoid action) is about 4.5 nM. These results suggested that the inhibition of ACTH by corticosterone might be mediated by association of the steroid with high affinity, type I corticosteroid receptors, whereas the inhibition of thymus weight and transcortin might be mediated by association of the steroid with lower affinity, type II receptors. The results of studies comparing the ability of corticosterone, dexamethasone and aldosterone to inhibit adrenalectomy-induced ACTH secretion support the hypothesis that basal ACTH secretion in rats is mediated by association of corticosterone with type I receptors.

Adrenalectomy↗

Plasma adrenocorticotropin is more sensitive than transcortin production or thymus weight to inhibition by corticosterone in rats.

After adrenalectomy, ACTH, corticosterone-binding globulin (CBG), and thymus wet weight increase in rats as a consequence of the removal of corticosterone (B) and decrease again in response to replacement with glucocorticoids. We have studied the effect of replacing adrenalectomized male rats with a variety of different concentrations of B. Plasma concentrations of ACTH and CBG and thymus wet weights were related to the measured concentration of free ultrafilterable B in plasma. In other experiments, the clearance of [125I]CBG was determined in adrenalectomized rats with and without B replacement, and the time required for the changes in plasma CBG concentrations after removal and/or replacement of B in adrenalectomized rats was determined. Five to 7 days after adrenalectomy and institution of a relatively constant B replacement signal, plasma CBG concentrations were highly correlated with circulating B concentrations (r2 = 0.745; P less than 0.001). The effect of B was on the CBG production rate, since clearance did not change. Because CBG concentrations decrease as total B concentrations increase, there is an amplification of free B concentrations with increasing total B. The relationships of plasma ACTH and CBG and thymus wet weight to circulating free B levels showed that 50% inhibition of ACTH was achieved at a free B concentration of 0.8 +/- 0.05 nM, whereas 50% inhibition of CBG and thymus wet weight were achieved at free B concentrations of 4.6 +/- 0.9 and 4.4 +/- 0.6 nM, respectively. These inhibition values correlate well with the known Kd values for the high affinity type I B receptor (0.5 nM) and for the lower affinity type II glucocorticoid receptor (2.5-5 nM), respectively, suggesting that ACTH secretion, CBG production, and thymus wet weight are regulated by the association of B with these receptor types.

Adrenalectomy↗

Energy intake and body weight in ovo-lacto vegetarians.

Vegetarians have a lower body weight than omnivores. In this study the relationship between the weight/height ratio and food consumption was evaluated in 92 ovo-lacto vegetarians and 113 omnivores in Israel. The average weight of the vegetarians was significantly lower than that of the omnivores (60.8 kg vs. 69.1 kg), even though the vegetarian diet supplied a significantly higher amount of calories than the nonvegetarian diet (3,030.5 cal/day vs. 2,626.8 cal/day). Consumption of fat was similar in both groups. Carbohydrate consumption was higher in the vegetarians while protein consumption was lower. The prevalence of obesity was significantly lower in the vegetarian group (5.4%) as compared to 19.5% among the omnivores. The lower body weight of vegetarians despite a higher caloric intake is of considerable interest.

Adult↗

Presence and identification of polyamines in xylem and Phloem exudates of plants.

Polyamines were identified by high performance liquid chromatography (benzoylation) and by thin layer chromatography (dansylation) in xylem exudates from stems of sunflowers (Helianthus annuus [L.]), mung bean (Vigna radiata [L.] Wilczek), grapevine (Vitis vinifera [L.] cv Grenache), and orange (Citrus sinensis [L.] Osbeck, cv Valencia), as well as in phloem sap (using elution into EDTA) of sunflower and mung bean plants. Putrescine was the major polyamine detected, ranging in concentrations of 150 to 9200 picomoles per milliliter exudate, whereas only trace amounts of spermine were detected. High amounts of putrescine and spermidine were found in EDTA eluates (possibly phloem sap) as compared with elution into water. Concentrations of putrescine and spermidine in xylem exudates were related to the physiological conditions of the plants prior to exudate collection. More putrescine was found in exudates of older than in younger sunflower plants, and salt stress applied to sunflower plants resulted in a higher concentration of putrescine and spermidine in the exudate. The presence and abundance of putrescine and spermidine in xylem and phloem exudates indicate that polyamines may be translocated in plants. This long-distance translocation further supports the hypothesis that polyamines have a regulatory role in plant growth and response to stress.

Journal Article↗

Reduced hyperpnea-induced bronchospasm following repeated cold air challenge.

This study assessed reduction in expiratory function in 12 asthmatic subjects both after 5 min of cold air provocation (CAP) with dry air conditioned to approximately 0 degrees C and after exercise (to 85% of predicted maximum heart rate) while breathing ambient room air (approximately 21 degrees C and 40% relative humidity). These assessments were done both before and after the following training protocol. Three 5-min periods of isocapnic cold air hyperpnea separated by 5-min rest periods were performed breathing 0 degrees to -10 degrees C air, for 36 sessions over 12 wk. As expected, pretraining expiratory function was significantly reduced (P less than 0.001) after both CAP and exercise. The posttraining reduction in expiratory function after CAP and exercise, however, was significantly less pronounced (largest P less than 0.05). These data support our hypothesis that repeated bouts of cold air challenge result in airway acclimatization to cold air and consequent decrease in exercise-induced bronchospasm. Acclimatization may result directly either by habituation of the airways or by vasodilation leading to increased bronchial blood flow and consequent reduced airway cooling. An unanticipated finding, though, is that repeated cold air challenge may also cause long-term inflammatory changes in the airways. A significant percentage of subjects experienced reduced base-line pulmonary function and overall exacerbation of asthma symptoms during the training period.

Acclimatization↗

Reset of feedback in the adrenocortical system: an apparent shift in sensitivity of adrenocorticotropin to inhibition by corticosterone between morning and evening.

There is evidence in man and rats that higher circulating levels of glucocorticoids are required to normalize basal unstimulated ACTH levels at the peak of the circadian rhythm than at the trough. To explore this phenomenon, we tested the inhibitory effect of constant levels of corticosterone on plasma ACTH in the morning (AM) and evening (PM) in young male rats implanted with fused pellets of corticosterone-cholesterol at the time of adrenalectomy (ADX+B) and studied 5 days later. There was a marked shift of the plasma corticosterone-ACTH inhibition curve to the right between AM and PM, demonstrating that the efficacy of corticosterone feedback inhibition of ACTH is less in the PM. Comparison of plasma ACTH and corticosterone levels during 24 h in sham-adrenalectomized rats (SHAM-ADX), adrenalectomized rats (ADX), and ADX+B revealed constantly low ACTH in SHAM-ADX, constantly high ACTH in ADX, and biphasic ACTH levels in ADX+B. Corticosterone levels were biphasic in SHAM-ADX and were constant in the other two groups. These results again showed a shift in corticosterone feedback efficacy as a function of the time of day and also suggested that basal ACTH secretion is maintained in the low normal range in intact rats because of the marked diurnal rhythm in corticosterone. The sensitivity of the pituitary ACTH response to exogenous CRF did not change between AM and PM in either intact or ADX+B showing that the shift in feedback sensitivity to corticosterone does not reside in the pituitary. The response of the entire adrenocortical system to histamine stress was shown to be equivalent in both the AM and PM, suggesting that feedback sensitivity of the entire system to corticosterone does not change as a function of the time of day. We conclude from these results that there is an apparent diurnal change in ACTH sensitivity to corticosterone feedback that can be defined operationally as reset. We believe that the site of feedback being tested shifts solely from the pituitary in the AM (at the nadir of the rhythm) to the brain and the pituitary in the PM (at the peak of the rhythm). The lack of the normally high transients of corticosterone that occur in SHAM-ADX rats results in increased brain drive of the pituitary in ADX+B.

Adrenal Cortex↗

Mineral intake and blood levels in vegetarians.

Concern has been raised that a long-term high-fiber diet may lead to mineral deficiencies. In this study, mineral intake and blood levels were investigated in 92 ovolacto vegetarians and 113 omnivores. The intake of iron, zinc, calcium and magnesium was adequate in both groups. The intake of iron and magnesium was significantly higher in the vegetarians. Mean blood levels of iron, iron binding capacity, calcium, phosphorus, alkaline phosphatase, zinc and magnesium were within normal limits in both groups. Serum magnesium levels were significantly higher in male vegetarians. Iron binding capacity was significantly lower in vegetarians of both sexes. It is concluded that a long-term ovolacto vegetarian diet does not lead to mineral deficiencies.

Adult↗

Corticotrope response to removal of releasing factors and corticosteroids in vivo.

In the intact rat, adrenalectomy (ADX) is known to result in increased ACTH synthesis, content, and secretion from the anterior pituitary compared with those in the sham-adrenalectomized control. Treatment of adrenalectomized, rats with corticosterone prevents or reverses these changes in ACTH. Because corticosterone is known to act both at the corticotrope and at the level of CRF secretion, it is not clear to what extent the ACTH response to ADX is a result of removal of glucocorticoids from the pituitary per se. To test the role of brain input as well as the role of glucocorticoids on the corticotrope response to ADX, we performed the following experiment. Rats were prepared with anterolateral hypothalamic deafferentations (lesion) which severed CRF and arginine vasopressin cell bodies in the hypothalamus from their axonal endings in the median eminence and posterior pituitary. Control rats were subjected to sham lesions. Two days later, half of the rats in each group were subjected to either ADX or sham ADX; a subgroup of the lesioned rats was provided at the time of adrenal surgery with a constant infusion of rat CRF. Five days later, all rats were killed, and anterior pituitary levels of proopiomelanocortin (POMC) mRNA, ACTH, and protein; plasma ACTH and corticosterone, and adrenal and thymus weights were measured. In sham-lesioned rats, ADX resulted in increases in POMC mRNA, and plasma ACTH of 2.5- and 12-fold, respectively, compared to sham-adrenalectomized controls. In the absence of hypothalamic drive (lesion only), there were no responses of any of these variables to ADX. In lesioned rats driven with CRF, ADX resulted in increases in POMC mRNA and plasma ACTH of 2.2- and 2.6-fold, respectively, compared to sham ADX. After consideration of the three variables indicating ACTH synthesis, storage, and secretion and comparison of the results of ADX vs. sham ADX within and across the sets of animals, we conclude that 1) there is no autonomous response of the corticotrope to ADX; 2) the removal of corticosterone from the anterior pituitary may account for the majority of the effects of ADX on ACTH synthesis; and 3) the normal response to ADX requires secretion of CRF and increased secretion of another ACTH-releasing factor (possibly arginine vasopressin) that causes increased secretion but little synthesis of ACTH.

Adrenal Glands↗

Nutritional status in elderly population in kibbutzim.

This study was conducted in order to assess the nutritional status of thiamin, riboflavin, pyridoxine, carotene, retinol, ascorbic acid, plasma iron, hemoglobin and plasma albumin of the elderly living in two cooperative farms (Kibbutzim), in Israel. Blood samples from elderly subjects aged 60 to 85 (33 women, 26 men), were collected for analysis. Thiamin, riboflavin and pyridoxine status were assessed by using enzymatic activation coefficient. Transketolase was used for determining thiamin status, glutathione reductase for determining riboflavin status and glutamate oxaloacetate transaminase for pyridoxine status. Transketolase activation coefficient ranged from 1.05-1.59 with a mean 1.18 and SEM 0.02, glutathione reductase coefficient ranged from 1.08-1.50 with a mean 1.25 and SEM 0.07 and glutamate oxaloacetate transaminase activation coefficient ranged from 1.71-2.15 with a mean 1.83 and SEM 0.06. Deficient levels were found in the following: Leucocyte ascorbic acid 5% of the population, hemoglobin 18%, plasma iron 20%, carotene 32% and plasma retinol 20%, thiamin 14% and riboflavin 32%. No deficient state was found in pyridoxine.

Aged↗

Pulmonary edema: reversal by ultrafiltration.

Ultrafiltration, the process by which plasma water is removed from the blood was utilized to determine its effect on lowering lung water in pulmonary edema produced by fluid overload, steam inhalation, and endotoxin. Lung water was measured by the thermal-dye indicator dilution technique which correlated well with lung water measured gravimetrically over a wide range (r = 0.95). Edema was produced by fluid overload in five mongrel dogs (Group I), by steam inhalation (Group II), and by endotoxin (Group III). Extravascular lung water (EVLW) rose significantly (P = less than 0.05) from control levels with the production of the edematous states (Group I: 8.0 ml/kg (mean) +/- 1.9 (SD) to 13.1 +/- 1.9); (Group II: 8.1 +/- 1.0 to 10.7 +/- 0.7); (Group III: 7.4 +/- 0.9 to 10.3 +/- 1.2). EVLW then fell significantly (P = less than 0.05) after ultrafiltration in all three groups (Group I: 8.9 +/- 2.4; Group II: 7.8 +/- 1.9; Group III: 7.7 +/- 1.4). Ultrafiltration was effective in reversing pulmonary edema and may have clinical application when excess lung water interferes with cardiac or pulmonary function.

Animals↗

Arginine and ornithine decarboxylases, the polyamine biosynthetic enzymes of mung bean seedlings.

General properties and relative activities of l-arginine decarboxylase (ADC) (EC 4.1.1.19) and l-ornithine decarboxylase (ODC) (EC 4.1.1.17), two important enzymes in putrescine and polyamine biosynthesis, were investigated in mung bean (Vigna radiata L.) tissues. Both activities increase linearly with increasing concentrations of crude enzyme, but the increase in ADC activity is considerably greater. The decarboxylation reaction is linear for up to 30 to 60 minutes, and both enzymes have a pH optimum of 7.2. alpha-Difluoromethyl-ornithine inhibits ODC activity of excised roots, while increasing ADC activity.High specific activity of both enzymes is detected in terminal buds and leaves, while root and hypocotyl activity is low. Different ADC-to-ODC activity ratios are found in various tissues of mung bean plants. Substantial increase in the activity of both enzymes is detected in incubated sections as compared with intact plants. A comparison of several plant species indicates a wide range of ADC-to-ODC activity ratio.It is suggested that both ADC and ODC are active in plant tissues and that their relative contribution to putrescine biosynthesis is dependent upon the type of tissue and growth process.

Journal Article↗

A high-fiber diet does not cause mineral and nutrient deficiencies.

We evaluated the hypothesis that a healthy population taking a high-fiber diet may develop deficiencies of various minerals and nutrients in three groups of healthy subjects: 1) sixty-eight people regularly supplementing their diet with at least 2 tablespoons of bran for at least 6 months (mean 3 tablespoons for 13 months); 2) forty-three controls not consuming bran supplements; and 3) twenty vegetarians (eight of them consuming bran supplements) who had a very high fiber consumption for many years. The mean serum levels of iron, total iron binding capacity, calcium, phosphorus, alkaline phosphatase, zinc, magnesium, vitamin A, and cholesterol were within the normal range in all the three groups. In the bran eaters, vitamin A was higher, and alkaline phosphatase and magnesium lower than in the other two groups. In the vegetarians, the phosphorus level was higher and cholesterol and iron binding capacity lower than in the other two groups. There was no correlation between the amount of bran consumed and the blood level of nutrients. The fiber consumption of the vegetarians was very high, more than three times that of the controls. Our study indicates that a moderately or even extremely high consumption of fiber for a long time does not by itself cause mineral or nutrient deficiencies in a western type population.

Adult↗

Comparison of the phosphorylation of human erythrocyte spectrin in the intact red cell and in various cell-free systems.

Knowledge of the position and characteristics of the four spectrin phosphorylation sites (Harris, H. W., Jr., and Lux, S. E. (1980) J. Biol. Chem. 255, 11512-11520) was used to study the kinetics of spectrin phosphorylation in the intact red cell. Incubation of intact erythrocytes in the presence of [32P]orthophoshate produced a simultaneous increase in the specific activities of all the spectrin phosphorylation sites. The dephosphorylation of spectrin followed an identical pattern. Spectrin phosphate turnover in intact red cells was then quantitatively compared to isotope labeling patterns produced by phosphorylation of spectrin in various cell-free systems ("in vitro phosphorylation"). 33P-Labeled spectrin dimer, prepared by preincubation of red cells in [33P]orthophosphate, was phosphorylated by a spectrin kinase preparation (Hosey, M. M., and Tao, M. (1977) Biochim. Biophys. Acta 482, 348-357) and [gamma-32P]ATP. Under conditions where no dephosphorylation occurred as judged by loss of 33P label, 0.46 +/- 0.1 mol of 32P-labeled phosphate was incorporated/mol of spectrin dimer. The exogenous 32P label was located in a position and ratio identical with that of the endogenous 33P lebel. Similar results were obtained when the membrane-bound spectrin present in ghosts was phosphorylated using the procedure of Birchmeier and Singer (1977) J. Cell Biol. 73, 647-659). These data indicate that within the intact red cell all of the spectrin phosphates possess an identical rate of isotope exchange and approximately 90% of the spectrin phosphorylation sites are occupied. The remaining 10% may be phosphorylated in vitro by soluble or membrane-bound spectrin kinase in a pattern that is identical with that of the intact erythrocyte.

Adenosine Triphosphate↗

Purine nucleoside phosphorylase activity in acute lymphoblastic leukemia.

Purine nucleoside phosphorylase (PNP) activity has been measured in the lymphoblasts of 22 patients with acute lymphoblastic leukemia (ALL) and correlated with routine immunologic cell surface markers. Fourteen of the 22 patients were considered to have non-T, non-B-cell ALL; 8 patients had T-cell disease. The median PNP activity in 21 control samples of normal peripheral blood mononuclear cells was 83 U. The median PNP activity of the non-T, non-B lymphoblasts was 79 U. No statistical difference in PNP activity between these two groups could be discerned (p < 0.37). In contrast, T-cell lymphoblasts demonstrated diminished PNP activity with a median of 38 U. The differences in activity between T lymphoblasts and both non-T, non-B leukemic cells and normal peripheral blood mononuclear cells were significant (p < 0.001 and p < 0.003, respectively). Evaluation of PNP activity provides further evidence of biochemical heterogeneity among immunologic subclasses of ALL.

Antigens, Surface↗