Greater Proportional Increase Research Articles

Attenuated Rise of 1,25 (OH)<sub>2</sub> Vitamin D<sub>3</sub> in Response to Parathyroid Hormone in Patients with Incipient Renal Failure

Despite elevated parathyroid hormone (PTH) levels, low normal or diminished serum 1,25(OH)2D3 concentrations are found in patients with incipient renal failure. To further assess (indirectly) the reserve capacity of renal production of 1,25(OH)2D3 we studied 9 patients with incipient or moderate renal failure (inulin clearance 31-68ml/min/1.73 m2) and 9 controls, using a novel stimulation test. We measured 1,25 (OH)2D3 levels, free 1,25(OH)2D3 index, cAMP excretion, calciuria and phosphaturia before and after infusion of 2 x 400 U of human (h) PTH (1-38). Baseline 1,25(OH)2D3 levels were not significantly different in patients (42.5 pg/ml, 21.6-51.1) compared with controls (45.0 pg/ml, 37.4-67.3). After infusion of hPTH(1-38), however, median increase in 1,25(OH)2D3 was only +25% versus +86% in controls, despite a greater proportional increase in cAMP/GF ratio. The data suggest subnormal stimulation of renal 1,25(OH)2D3 production in response to exogenous PTH in most patients with incipient renal failure. This may reflect partial exhaustion of biosynthetic reserve capacity.

Effects of feeding condition on orally delivered ethanol as a reinforcer for rhesus monkeys

Twenty adult male rhesus monkeys could drink either or both an 8%-ethanol (w/v) solution or water during daily 3-h experimental sessions. Subjects were initially tested under ad lib feeding conditions, having received daily access to large amounts of food for approximately 8 months (Phase 1). The ethanol solution was concurrently available with its water vehicle under fixed-ratio schedules of mouth contacts with a drinking spout in which emission of 8 responses produced a liquid delivery (FR 8). Under these conditions ethanol served as a reinforcer for some subjects--it maintained higher response rates than water--but not for others. In the next experimental condition (Phase 2), subjects were again tested for ethanol self-administration under FR 8 schedules with water concurrently available, but while receiving daily food rations that maintained their body weights at less than what they had been under ad lib feeding conditions. Under these conditions all subjects self-administered ethanol at appreciable levels, but water-maintained responding also was at appreciable levels for some subjects. Increases in ethanol self-administration following institution of the reduced-feeding conditions in Phase 2 generally were inversely related to self-administration levels under the free-feeding conditions of Phase 1 (the greatest proportional increases in ethanol intake occurred with those monkeys that self-administered the least amount of ethanol in Phase 1). In Phase 3, the requirements of the concurrently operating fixed-ratio schedules delivering ethanol and water were increased to 16 responses (FR 16).(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic disposition and pharmacokinetics of pelrinone, a new cardiotonic drug, in laboratory animals and man

The metabolic disposition of pelrinone, a cardiotonic drug, was studied in mouse, rat, rabbit, dog, monkey and man. Pelrinone was rapidly and extensively absorbed in rodents, dogs, monkeys and man. Except in rabbits, the major portion of the serum radioactivity was due to parent drug. Pelrinone was moderately bound to human serum proteins and weakly bound to serum proteins from animals. Radioactive compounds were rapidly eliminated from rat tissues with the highest concentrations found in organs associated with absorption and elimination. After a 1.0 mg/kg i.v. dose, the rapid elimination of pelrinone from mouse, rat and dog serum precluded estimation of an elimination half life (t1/2). However, after higher oral or i.v. doses, a more prolonged elimination phase was apparent and the t1/2 of pelrinone ranged from 8-10 h in rodents and dogs. In human subjects given escalating oral or i.v. doses of pelrinone, the elimination t1/2 was independent of dose and averaged 1-2 h. The serum AUC of pelrinone was linearly dose-related following oral doses up to 20 mg/kg in dogs and 100 mg in man. In mice, a greater proportional increase in AUC occurred between oral doses of 2-100 mg/kg while in rats, the serum AUC increased in less than proportional manner from 10-200 mg/kg p.o. In all species, radioactive compounds were excreted mainly in the urine. No metabolites were detected in dog and human urine while small amounts of unconjugated metabolites were excreted in mouse and rat urine.

A Component Analysis of the Room Manager Role

A component analysis of the room manager role (Porterfield et al., 1980) was performed in a series of four experiments. The subjects were one nursing staff and 13 severely and profoundly mentally handicapped young adults. The experiments took place in a hospital adult training unit. Five components (presence of toys in the room, providing a toy, replacing toys, prompting, and the full room manager role) were compared. Increases in the proportion of time on task were associated with the antecedents; praising had no effect. For residents with high Vineland Social Age regularly replacing toys was associated with the greatest increase in the proportion of time on task. For residents with low Vineland Social Age prompting was associated with the greatest increase in proportion of time on task. Implications for modification of the room manager role are considered and limitations to the present study discussed.

The effects of a combined implant of trenbolone acetate and oestradiol-17 beta on protein and energy metabolism in growing beef steers.

1. The effects on growth performance, energy and nitrogen retention, and leucine metabolism of a subcutaneous combined implant of 140 mg trenbolone acetate (TBA)+ 20 mg oestradiol-17 beta (OE) have been examined in Hereford x Friesian beef steers (280-520 kg). Comparisons were made both with the same animals before implantation and with untreated control animals maintained under similar physiological and nutritional conditions. 2. Over a 10 week period the implanted steers showed an improvement in rate of live-weight gain (LWG) of 0.5-0.6 with an even greater proportional increase in N retention compared with control animals. Total energy retention was unaffected and thus the ratio, protein energy: total energy gain was 0.43 for implanted steers compared with 0.26 for untreated animals. 3. Estimates of protein synthesis and protein oxidation were obtained from the specific radioactivities of blood free-leucine and exhaled carbon dioxide during continuous infusions of [1-14C]leucine. Whole-body protein synthesis, based on metabolic size, and amino acid fractional oxidation remained similar for control steers throughout the experiment. Steroid-treated steers showed a slight decline in synthesis which was significant (P less than 0.05) at week +5 post-implant while amino acid oxidation was significantly lower at weeks +2 (P less than 0.01) and +5 (P less than 0.05) compared with control animals. The ratio, protein deposition: protein synthesis was 0.05 for control animals but 0.08-0.10 for steroid-treated animals after implantation. 4. There was a slight decrease in urinary N tau-methylhistidine elimination after implantation which suggested that muscle protein degradation may be reduced although the estimated decrease was insufficient to account for the total improvement in growth rate and N retention. 5. The results suggest that for both control and treated steers, less than 0.5 of total urine N elimination was derived directly from tissue catabolism of protein and amino acids. 6. The combined action of the exogenous steroids in the promotion of protein gain, primarily through a decrease in total protein degradation with little alteration of total energy retention, is compared with present understanding of the role of the endogenous sex hormones.

Relative slowness of heterotypic synaptogenesis in the septal nuclei

The dorsolateral quadrant of the lateral septal nucleus receives a bilateral projection from the fimbria. When the fimbria of one side is cut, the axons of the remaining fimbria take over its synaptic sites preferentially, but when both fimbrias are cut the sites are reinnervated by a non-fimbrial axons. To explores the basis of this preference, the present study plots the time courses of the appearance and disappearance of degenerating synapses, and the loss and recovery of non-degenerating synapses after ipsi-, contra- and bi-lateral fimbrial lesions. A preliminary investigation showed that at any time after these three lesions there was no change in the numerical density per unit area of ‘control’ structures such as shaft synapses (which do not degenerate) and neuronal perikarya (which neither shrink nor degenerate). This indicates that the changes in the numerical density of fimbrial (spine) synapses can be used as a measure of the processes of deafferentiation and reinnervation without the danger of the numerical data being distorted by shrinkage. In the sampled area, the ipsilateral fimbrial axons account for about 45% of the synapses and the contralateral fimbrial axons for 25%. The number of degenerating synapses appearing at any one time underestimates the loss of non-degenerating synapses by about one-third, and a photographic simulation of degeneration suggests that a major factor in this discrepancy is the difficulty in recognizing degenerating synapses. Our main finding is that there is a major delay in the rate of removal of degeneration, and in the rate of reinnervation, after bilateral as opposed to unilateral lesions. This delay cannot be accounted for in any simple way by the greater amounts of degeneration. Thus after unilateral lesions, which cause the turnover of 25% (contralateral) or 45% (ipsilateral) of the synapses, 50% of the degeneration is removed in 1–2 days after the peak, whereas after bilateral lesions, which affect 70% of the synapses, it takes 20 days for 50% of the degeneration to be removed. That the synaptic changes after bilateral lesions involve a qualitatively different mechanism is also suggested by the observations of a much greater proportional increase in the multiple synapse index, and a decreased astroglial response.

Cholinergic enzyme activity in neurons of the developing anuran spinal cord.

Cholinergic enzyme activity was investigated over the course of spinal cord development from early larval (tadpole) stages to adult life in bullfrogs (Rana catesbeiana). Acetylcholinesterase (AChE) activity examined histochemically in spinal neurons and AChE and choline acetyltransferase (ChAT) activities were measured biochemically in axons of developing hindlimb motoneurons. At early larval stages, only spinal neurons born during embryonic life (primary neurons) showed histochemical evidence of AChE activity. Hindlimb motoneuron somata did not show AChE activity until mid-larval stages. AChE and ChAT activities were found in hindlimb motoneuron axons at the earliest stages examined, when the hindlimb consists of a small bud of undifferentiated mesenchyme. Activities of both enzymes show steady increases over the course of development until climax, when activities maintain a plateau until metamorphosis is complete. Total activities of both enzymes increase as the adult frog grows, although ChAT activity shows a much greater proportional increase than AChE activity.

Habitable Pore Space and Microbial Trophic Interactions

Microbial trophic structure and available soil pore space influence rates of decomposition and mineralization. The nematode (Mesodiplogaster) used feeds on bacteria (Pseudomonas) as well as amoebae (Acanthamoeba) but grows best in the presence of amoebae. Respiration rates were higher when both grazers were grown with bacteria (food web) than when grazers were grown singly with bacteria (simple food chain). We hypothesized that one reason for increased nematode growth in the presence of amoebae is that protozoa make food more available to nematodes by entering soil pores inaccessible to nematodes, feeding on bacteria within the pores, and emerging as food otherwise unavailable to nematodes. To test this possibility, we designed an experiment using a fine-textured (with fewer habitable pores for nematodes) and a coarse-textured soil. There was a greater proportional increase in nematode growth with amoebae in the fine than in the coarse soil. We conclude that microbial trophic structure in relation to soil texture and habitable pore space is an important factor influencing energy flow in terrestrial ecosystems.

Importance of the Tip on the (5-3H)-Indol-3yl-acetic Acid Transport in Maize Root

Summary Basipetal and acropetal movement of radioactivity from (5- 3 H)-IAA (10 -7 M) was followed for 1 and 3 hours in intact or decapitated 10 mm apical maize root segments. Beside a weak acropetal transport - significant radioactivity could only be detected in apical receivers on decapitated segments - a typical basipetal movement was also obtained. A clear acropetal polarity was only observed in root tissues near the receiver blocks, the presence of the root tip significantly reducing such polarity. Chromatographic analyses of root extracts showed a great increase in IAA proportion in function of the distance counted from the tip.

3H‐URIDINE INCORPORATION IN THE PREMITOTIC STAGE OF RHIZOID CELL DIFFERENTIATION IN PTERIS VITTATA L.

The premitotic rhizoid stage (corona stage) of P. vittata gametophytes was pulsed in radioactive uridine for 5, 15, or 30 min and the data analyzed quantitatively by autoradiography. After 5 min, only the nucleoplasmic compartment is labelled significantly, suggesting that this short pulse is insufficient time for labelled precursor to be fixed in the nucleolus or to be transported from the nucleus to the cytoplasm. Since after 15 and 30 min, all compartments are labelled, with the greatest proportional increase over the nucleolus, it is concluded that cytoplasmic labelling is nuclear in origin and that nucleolar RNA activity is relatively high in this stage.

Salt Stress and Comparative Physiology in the Gramineae. II. Glycinebetaine and Proline Accumulation in Two Salt- and Water-Stressed Barley Cultivars

Under low-salt conditions, the glycinebetaine levels in the shoot exceeded the proline levels in two barley cultivars, California Mariout and Arimar. Stress induced by both polytheylene glycol (PEG) and NaCl caused an accumulation of both compounds. However, a gradual incremental increase in stress led to higher glycinebetaine than proline levels, whereas salt and osmotic shock led to proline levels far in excess of the glycinebetaine levels. Both stress regimes caused a greater proportional increase in proline than in glycinebetaine. Preliminary data suggest that proline may be used as an internal assay for water stress in barley leaves. Comparison of the physiological responses of the barley cultivars to NaCl and PEG stress suggested that the suppression of growth by salt treatment was not due directly to the low external water potential but arose either from the ions, Na+ and Cl-, interfering with metabolic processes or from a number of possible but unsubstantiated interactions leading to a reduction in turgor potential and thus in the rate of cell expansion.

Distribution of 3':5'-cyclic AMP and 3':5'-cyclic GMP in rabbit retina in vivo: selective effects of dark and light adaptation and ischemia.

By use of highly sensitive radioimmunoassays, 3':5'-cyclic AMP (cAMP) and 3':5'-cyclic GMP (cGMP) were measured in individual layers of light- and dark-adapted rabbit retinas, and the effects of ischemia were determined. In light-adapted retinas, cGMP levels ranged 50-fold, with over 90% of the total concentrated in the photoreceptor cells. The layer of outer segments contained 95 mumol/kg of dry weight, or three times the concentration present in the remainder of the photoreceptor cell layers. By contrast, levels of cAMP varied only 4-fold; the lowest level (6 mumol/kg of dry weight) was found in the outer segment layer and the highest level (22 mumol/kg of dry weight) in the inner segment layer of the photoreceptor cells. Dark adaptation elevated cGMP levels only in retinal layers containing photoreceptor cells, and the greatest proportional increase was observed in the synaptic layer of photoreceptor cells. Dark adaptation also caused increases of cAMP that were restricted to the outer plexiform and outer nuclear layers. Ischemia lowered cGMP levels, but only in retinal layers containing photoreceptor cells, and elevated cAMP levels, primarily in the inner layers of the retina. The effects of ischemia were greater in the dark-adapted than in light-adapted retinas. These results indicate that cGMP and cAMP levels in retina are influenced by the light adaptational state, that ischemia markedly modifies these processes, and that the effects of both light exposure and ischemia are regionally selective.

Changes in the rumen metabolism of sheep given increasing amounts of linseed oil in their diet.

1. Linseed oil was incorporated gradually into the diet of four sheep until the animals received 90 g additional fat/d. Attempts were made to measure changes in concentration of substances and rates of synthesis in the rumen directly, and by incubation of rumen contents in vitro (zero-time technique). 2. The high-fat diet increased the dilution rate and the volume of rumen contents and decreased the synthesis of diaminopimelic acid in the rumen. The number of protozoa decreased and the number of bacteria increased in the rumen of animals receiving the high-fat diet. 3. The concentration of volatile fatty acids (VFA) in the rumen decreased for sheep given the high-fat diet, but the capacity of rumen contents to produce VFA in vitro increased. 4. The incorporation of radioactivity from [14C]acetate into lipids during incubation of rumen contents vitro increased with the amount of linseed oil in the diet. The greatest proportional increase was with the bacterial fraction of rumen contents. 5. In the group of four animals used, one animal showed consistent differences in the magnitude of the measured varibles. This animal appeared to have a smaller rumen, a lower dilution rate and larger concentrations of some substances in the rumen. A higher proportion of fatty acids appeared to be synthsized by the micro-organisms from this animal.

Studies of nonmigrating, long-lived lymphocytes in rats: I. Reactions after antigenic challenges in situ

In a search for a noncirculating mechanism of immunologic memory, popliteal lymph node cells were labeled with tritiated thymidine after a primary immune stimulus with polymerized Salmonella flagellins and were challenged with a variety of antigens 45 days later. The appearance of increased numbers of labeled large lymphoid cells in situ, i.e. lymphoblasts and plasmablasts, 48 hr after an antigenic stimulus, and their ability to produce antibody were used as criteria for judging the response of noncirculating, long-lived small lymphocytes to the challenge. Little or no effect of specific or nonspecific antigens was seen on the numbers of persisting labeled small lymphocytes in situ. There were increases in the numbers of and in the mean grain counts of labeled large lymphoid cells after all challenging stimuli, including BSA and SRBC. A small but significantly greater increase in proportion of labeled large lymphoid cells appeared after immunologically specific challenges than after nonspecific challenges. Virtually none of those large cells derived from long-lived lymphocytes were capable of causing specific bacterial adherence. In contrast, cells labeled with 125I-UdR 2 hr before challenge could cause immunologically specific bacterial adherence. Most were found when a secondary challenge was given, but some cells were also found after a primary challenge. We conclude that this work makes unlikely those theories of immunologic memory involving sequential development of a single cell line. We reopen the question whether some of the precursors of functional plasma cells are a continuously dividing cell line in a secondary response, pointing out that this is quite consistent with the current information implicating a two-cell system in immunologic memory.

A study of pre-natal growth and development in the sheep

A study of pre-natal growth and development in the sheep