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Biomedical subjects

M Padilla

Publications and source records attributed to M Padilla.

34 records · Page 2Linked to original sources

Aminoaciduria of vitamin D deficiency is independent of PTH levels and urinary cyclic AMP.

Aminoaciduria and secondary hyperparathyroidism accompany vitamin D deficiency. However, the degree of aminoaciduria and PTH elevation have not been studied relative to different calcium and phosphorus dietary intakes. Weanling rats were fed 5 vitamin D deficient diets for 4-6 weeks: very low Ca (VLC) 0.02% Ca, 0.3% P; VLC + 1,25-dihydroxyvitamin D [1,25(OH)2D3], same + 500 pmol i.p. for 2 days; low Ca (LC) 0.45% Ca, 0.3% P; very low P (VLP) 1.2% Ca, 0.1% P; high Ca (HC) 2.5% Ca, 0.3% P, and control 1.2% Ca, 0.70% P + 2.5 micrograms% vitamin D. Amino acids, serum 25-hydroxyvitamin D [25(OH)D3], 1,25(OH)2D3, and PTH, using a specific antirat PTH antibody, were measured. A significant generalized aminoaciduria (11 amino acids) was found in all vitamin D-deficient groups. Furthermore, it was independent of plasma Ca and PTH, and urinary cAMP excretion irrespective of diet. Serum 25(OH)D and 1,25(OH)2D were significantly reduced in all vitamin D-deficient groups. VLC and VLC + 1,25(OH)2D3 were associated with the highest PTH levels (10- and 13-fold increase, respectively) and urinary cAMP (2.3-fold increase in each) and the lowest serum Ca. LC rats had an 8.8- and a 1.7-fold increase in PTH and urinary cAMP, respectively. Phosphate depletion was found in VLP rats documented by insignificantly elevated PTH, normal urinary cAMP, hypercalciuria, and percent tubular reabsorption of phosphate of greater than 99%. While dietary Ca and P affect plasma and urinary Ca and P plasma PTH and urinary cAMP, it appears that dietary P affects the aminoaciduria observed in this study via mechanisms that remain unclear. The possibility that the mechanism for the tubulopathy is multifactorial should be entertained.

Amino Acids↗

Asbestos effects on superoxide production. An in vitro study of hamster alveolar macrophages.

Inhaled asbestos induces accumulation of alveolar macrophages (AM) and polymorphonuclear leukocytes (PMN) in lung. Asbestos-enhanced production of superoxide anion (O2-) by AM and/or PMN may be involved in the pathogenesis of asbestos-induced fibrosis, either through direct effects on collagen synthesis or via mediation of tissue injury and repair. In in vivo experiments, bronchoalveolar lavage (BAL) 3 to 8 weeks following intratracheal asbestos injections showed increases in both PMN and AM, with AM representing 78 to 82% of cells recovered. Inhalation models, generally regarded as more analagous to human exposures, have confirmed AM as the predominant component of the cellular response to inhaled asbestos. In this study, the in vitro effects of asbestos fiber on O2- production by AM have been determined in cell populations derived from the Syrian golden hamster. AM for in vitro study were obtained by BAL. O2- production was monitored as superoxide dismutase (SOD) - inhibitable cytochrome c reduction. Significant rises in O2- release by AM were noted in the presence of 0.4 mg/ml crocidolite (2.53 +/- 0.33 nmole cytochrome c reduced/10(6) cells/30 min, 37 degrees C; controls 1.13 +/- 0.18 nmole; P less than 0.02). Chrysotile induced levels of O2- release in AM which were similar to those evoked by crocidolite.

Animals↗

Studies on renal adaptation to altered dietary amino acid intake: tissue taurine responses in nursing and adult rats.

This study examines the effect of a low sulfur amino acid diet (LTD) and a high taurine diet (HTD), compared with a normal diet, on the plasma, urine, muscle, brain and renal cortex levels of taurine in immature and adult rats. Milk taurine from lactating dams reflected the taurine content of the diet, being low in LTD-fed and high in HTD-fed animals. Nursing pups (7, 14 and 21 d old) often had plasma, urine and tissue--renal cortex, heart, skeletal muscle--levels of taurine related to dietary exposure, a situation also found in adult animals. These diets did not influence the urinary excretion of the sulfur-containing alpha-amino acids methionine and cystine but a sulfur aminoaciduria of immaturity was evident. By contrast, the content of taurine in brain was constant regardless of dietary intake of sulfur amino acids. An age-related decline in brain taurine content was found--as noted by others--but this too was influenced by diet. This dual finding of brain taurine constancy despite wide differences in sulfur amino acid intake and changes in the renal handling of taurine as influenced by diet suggest that the renal adaptive response serves to maintain the stability of brain taurine content.

Adaptation, Physiological↗

Effect of amino acid intake on brush-border membrane uptake of sulfur amino acids.

Alterations in the intake of sulfur amino acids (SAA) changes the rat renal brush-border membrane uptake of the beta-amino acid, taurine. A low-SAA diet enhances and a high-taurine diet reduces uptake (Chesney et al., Kidney Int. 24: 588-594, 1983). Neither the low-SAA diet nor the high-taurine diet alters the time course or concentration-dependent accumulation of the sulfur amino acids methionine and cystine or of inorganic sulfate. By contrast the uptake of beta-alanine, another beta-amino acid that competes with taurine, is greater in animals on the low-SAA diet. The high-taurine diet does not change beta-alanine uptake. The plasma levels of taurine are altered by dietary change, but not the values for methionine and cystine. This study indicates that renal adaptation is expressed for beta-alanine, a nonsulfur-containing beta-amino acid. By contrast, methionine, cystine, and sulfate, which participate in a variety of synthetic and conjugative processes, are not conserved by the renal brush-border surface following ingestion of either a low-methionine and -cystine diet or high-taurine diet.

Amino Acids↗

Developmental aspects of renal beta-amino acid transport. V: Brush border membrane transport in nursing animals--effect of age and diet.

This study examines the Na+-dependent accumulation of the beta-amino acid, taurine, by brush border membrane vesicles isolated from nursing animals compared to uptake in adult animals. The diets fed to the mothers nursing these pups were altered so as to provide a low sulfur amino acid intake or a high taurine diet as well as conventional sulfur amino acid intake. Taurinuria is greater in nursing animals than in adult controls, but animals of all ages respond to exposure to the low sulfur amino acid intake by conservation of taurine and to the high taurine diet by hyperexcretion of taurine. Taurine uptake at 10 microM by brush border membrane vesicles is influenced by age in all groups and by diet in 14- and 21-day-old animals. A precession of uptake is seen both in terms of initial and peak rate of uptake with the lowest values in 7-day-old animals to the highest in adult. Greater brush border membrane vesicle uptake is found in 14- and 21-day-old rats after exposure to the low sulfur amino acid intake and reduced uptake after the HTD, whereas no dietary influence on uptake was found in 7-day-old rats. Neither the pattern of the time course of uptake nor the uptake values at equilibrium (45 min) are affected by age or diet. Kinetic analyses of concentration dependent uptake show that the maturational process involves a change in the Vmax of initial uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Factors affecting the transport of beta-amino acids in rat renal brush-border membrane vesicles. The role of external chloride.

The effect of a variety of ions and other solutes on the accumulation of the beta-amino acid, taurine, was examined in rat renal brush-border membrane vesicles. Initial taurine uptake (15 and 30 s) is sodium-dependent with a typical overshoot. This Na+ effect was confirmed by exchange diffusion and gramicidin inhibition of taurine uptake. External K+ or Li+ do not increase taurine accumulation more than Na+-free mannitol, except that the combination of external K+ and Na+ in the presence of nigericin enhances uptake. Of all anions tested, including more permeant (SCN- and NO3-) or less permeant (SO4(2-)), chloride supported taurine accumulation to a significantly greater degree. Preloading vesicles with choline chloride reduced taurine uptake, suggesting that external Cl- stimulates uptake. Since this choline effect could be related to volume change, due to the slow diffusion of choline into vesicles, brush-border membrane vesicles were pre-incubated with LiCl, LiNO3 and LiSO4. Internal LiCl, regardless of the final Na+ anion mixture, reduced initial rate (15 and 60 s) and peak (360 s) taurine uptake. Internal LiNO3 or LiSO4 with external NaCl resulted in similar or higher values of uptake at 15, 60 and 360 s, indicating a role for external Cl- in taurine uptake in addition to Na+ effect. Although uptake by vesicles is greatest at pH 8.0 and inhibited at acidic pH values (pH less than 7.0), an externally directed H+ gradient does not influence uptake. Similarly, amiloride, an inhibitor of the Na+/H+ antiporter, had no influence on taurine accumulation over a wide variety of concentrations or at low Na+ concentrations. Taurine uptake is blocked only by other beta-amino acids and in a competitive fashion. D-Glucose and p-aminohippurate at high concentrations (greater than 10(-3) M) reduce taurine uptake, possibly by competing for sodium ions, although gramicidin added in the presence of D-glucose inhibits taurine uptake even further. These studies more clearly define the nature of the renal beta-amino acid transport system in brush-border vesicles and indicate a role for external Cl- in this uptake system.

Amiloride↗

Localized lymphoid nodules of lung. A reappraisal of the lymphoma versus pseudolymphoma dilemma.

Eleven patients with localized lymphoid nodules of the lung (LLN) were seen at the Mount Sinai Hospital from 1962-1981. The diagnosis of pseudolymphoma was made in six instances based on the following criteria: (1) solitary or multiple nodules discovered on chest roentgenograms composed of cytologically benign lymphoid cells (small lymphocytes); (2) polymorphic character of the infiltrate, including plasma cells, histiocytes and monocytes; and (3) presence of germinal centers in the lesion. Five lesions were classified as lymphomas and exhibited: (1) solitary or multiple nodules composed of atypical lymphoid cells; (2) absence of germinal centers; (3) lack of mediastinal lymph node involvement. Bronchial and/or pleural infiltration by lymphoid cells was present in lymphomas as well as in pseudolymphomas. Five lesions were studied with immunofluorescent techniques for the presence of intracytoplasmic immunoglobulins and in one pseudolymphoma, lymphocyte marker studies were performed. The procedures were not useful in separating benign from malignant lesions. All patients underwent surgery; three with lymphoma and one with pseudolymphoma received adjuvant chemotherapy. Patients were followed post surgically for up to 13 years. None of the six patients with pseudolymphoma died as a result of their lesions but two had either recurrences or developed extrapulmonary lymphoid lesions. All five lymphoma patients did well. Only one died while on chemotherapy with invasive pulmonary aspergillosis but no tumor. One-hundred and sixty-seven reported cases from the literature are analyzed. Pulmonary pseudolymphomas do not necessarily follow a benign course and malignant lymphomas limited to the lungs do not usually undergo progressive disease. Present pathologic criteria do not allow prediction of recurrence or progression of disease and are not acceptable for determining the advocacy of chemotherapy in patients with LLN.

Aged↗

Renal adaptation to alteration in dietary amino acid intake.

The nonessential beta-amino acid taurine, which is inert in renal tissue, was used to study the renal adaptation to dietary taurine change. Three isoproteinic diets were employed: HTD--high in taurine, NTD--normal taurine, and LTD--deficient in the taurine precursors cysteine and methionine. When compared with NTD, HTD resulted in an increase in the urinary excretion and fractional excretion of taurine, whereas LTD led to a decrease in urinary excretion and fractional excretion of taurine. In vitro studies demonstrated an increase in the Vmax of the high-affinity, low-capacity uptake system with no change in "apparent" Km following LTD. Complete adaptation developed within days after the diet was changed (NTD to HTD = 3 days; NTD to LTD = 3-6 days). These studies demonstrate that the renal response to altered dietary amino acid can be evaluated and that adaptation occurs for the beta-amino acid taurine. The renal response serves to conserve taurine during periods of deprivation and to dispose of taurine during periods of excess. The renal adaptation to restricted taurine intake seems to occur through an increase in transport sites (increased Vmax) or change in flux at the transport sites, with no change in transport affinity (unaltered apparent Km).

Aging↗

Effect of allergic bronchoconstriction on airways epithelial permeability to large polar solutes in the guinea pig.

The effect of allergic bronchoconstriction on the permeability of the airway mucosa to large hydrophilic polar solutes was investigated in the guinea pig. After specific antigen (ovalbumin) challenge, there was a significant increase in the plasma levels of horseradish peroxidase (HRP) (molecular weight, approximately 40,000 daltons), 3H-dextran (approximately 10,000 daltons), and 14C-mannitol (approximately 182 daltons) compared with that in control animals aerosol-challenged with a nonspecific protein, lactoglobulin. The morphologic correlates of this enhanced transepithelial permeability after ovalbumin challenge appeared to be (1) increased HRP penetration of the epithelial tight junctions (p less than 0.001), and (2) increased mucus discharge from surface lining goblet cells. We conclude that antigen-induced bronchoconstriction leads to an increase in tracheobronchial permeability to macromolecules, and this effect is likely to be mediated by an increased paracellular as well as transcellular vesicular movement of large polar solutes across the airway epithelial barrier.

Animals↗

Training personnel in the prevention and management of violent behavior.

The authors describe a training program on prevention and management of violent behavior for the staff of a Veterans Administration hospital. The one-day workshop focuses on preventive identification of potentially violent situations and on methods of verbal and physical management of violent behavior. A study of workshop participants showed that trainees had improved knowledge about and performance in handling violent behavior after completing the program. Future developments in training in prevention and management of violent behavior should include greater availability of educational resource materials and incorporation of the subject in undergraduate and graduate health care training.

Humans↗

Calcium and 24,25-dihydroxyvitamin D: inverse relation in cows with parturient paresis.

Recent work suggests a role for 24,25-dihydroxyvitamin D in inhibiting mobilization of bone. This study was undertaken to investigate its possible role in the etiology of parturient paresis, a hypocalcemic condition of dairy cows occurring at the onset of lactation. This metabolic disease was chosen to serve as a model of impaired mineral homeostasis. The animals examined were parturient Holstein cows with (N = 6) and without (N = 7) parturient paresis. Determinations of serum 1,25-dihydroxyvitamin D, serum 24,25-dihydroxyvitamin D, and serum calcium were used to evaluate the 2 groups. The hormones were isolated using methylene chloride:methanol extraction, Sephadex LH-20 chromatography, and high-pressure liquid chromatography (HPLC). Quantitation was by competitive protein binding assays. Serum 1,25-dihydroxyvitamin D levels of affected cows were not significantly different from those of normal cows. The 24,25-dihydroxyvitamin D levels of paretic cows (3.48 +/- 0.27 ng/ml) were significantly higher than in the normal cows (2.03 +/- 0.34 ng/ml) (p less than 0.01). Linear regression analysis of the data from the paretic cows revealed an inverse relationship between serum calcium and 24,25-dihydroxyvitamin D (r = -0.94). This negative correlation between serum 24,25-dihydroxyvitamin D and serum total calcium in a naturally occurring hypocalcemic disease of dairy cattle may provide evidence that this metabolite is of significance in the etiology and pathogenesis of this syndrome.

24,25-Dihydroxyvitamin D 3↗

Initiation factor eIF-4B (IF-M3)-dependent recognition and translation of capped versus uncapped eukaryotic mRNAs.

Translation of capped and uncapped eukaryotic mRNAs is stimulated by addition of eIF-4B to an mRNA-dependent reticulocyte lysate system. m7G5 ppp inhibits translation of capped but not uncapped mRNAs and reduces translation of capped vaccinia mRNA to the level obtained with uncapped vaccinia mRNA. Exogenous eIF-4B but no other initiation factor reverses inhibition of protein synthesis by m7G5'ppp. Both capped and uncapped mRNAs interact directly with eIF-4B to form a stable complex, which can be detected by a simple nitrocellulose filter binding assay. However, addition of a 5'-cap to beta-eliminated globin mRNA or satellite tobacco necrosis virus RNA (normally uncapped) increased binding affinity of these mRNAs for eIF-4B and causes binding of these mRNAs to become sensitive to inhibition by m7G5'ppp. These results indicate that the role of the mRNA 5'-cap in translation is related specifically to the function of eIF-4B in forming a complex with mRNA (prior to association of mRNA with the 40 S ribosomal subunit) and that both cap and non-cap sequences participate in this process.

Animals↗