Restoring hope: lifting the ban on fetal tissue transplantation research.
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Abortion, Legal↗
Biomedical subjects
B Adams
Publications and source records attributed to B Adams.
Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis.
BSAP has been identified previously as a transcription factor that is expressed at early, but not late, stages of B-cell differentiation. Biochemical purification and cDNA cloning has now revealed that BSAP belongs to the family of paired domain proteins. BSAP is encoded by the Pax-5 gene and has been highly conserved between human and mouse. An intact paired domain was shown to be both necessary and sufficient for DNA binding of BSAP. Binding studies with several BSAP recognition sequences demonstrated that the sequence specificity of BSAP differs from that of the distantly related paired domain protein Pax-1. During embryogenesis, the BSAP gene is transiently expressed in the mesencephalon and spinal cord with a spatial and temporal expression pattern that is distinct from that of other Pax genes in the developing central nervous system (CNS). Later, the expression of the BSAP gene shifts to the fetal liver where it correlates with the onset of B lymphopoiesis. BSAP expression persists in B lymphocytes and is also seen in the testis of the adult mouse. All of this evidence indicates that the transcription factor BSAP may not only play an important role in B-cell differentiation but also in neural development and spermatogenesis.
Amino Acid Sequence↗
The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP.
The CD19 protein is expressed on the surface of all B-lymphoid cells with the exception of terminally differentiated plasma cells and has been implicated as a signal-transducing receptor in the control of proliferation and differentiation. Here we demonstrate complete correlation between the expression pattern of the CD19 gene and the B-cell-specific transcription factor BSAP in a large panel of B-lymphoid cell lines. The human CD19 gene has been cloned, and several BSAP-binding sites have been mapped by in vitro protein-DNA binding studies. In particular, a high-affinity BSAP-binding site instead of a TATA sequence is located in the -30 promoter region upstream of a cluster of heterogeneous transcription start sites. Moreover, this site is occupied by BSAP in vivo in a CD19-expressing B-cell line but not in plasma or HeLa cells. This high-affinity site has been conserved in the promoters of both human and mouse CD19 genes and was furthermore shown to confer B-cell specificity to a beta-globin reporter gene in transient transfection experiments. In addition, BSAP was found to be the only abundant DNA-binding activity of B-cell nuclear extracts that interacts with the CD19 promoter. Together, this evidence strongly implicates BSAP in the regulation of the CD19 gene.
Animals↗
Restraint-review committee: a working model.
Initially, the goal of this committee was to reduce the number of unnecessary physical restraints (see Table 4). This was achieved by a team approach and a systematic process of assessment, monitoring, and evaluation. In addition, this process provided a means by which restraint use could be thoroughly documented and functionally monitored. Efforts are continuing in order to provide a safe environment while at the same time promoting quality of life through reduction of restraints.
Aged↗
Effect of amiloride on diaphragmatic contractility: evidence of a role for Na(+)-Ca2+ exchange.
Extracellular Ca2+ has been shown to be important for the normal function of the diaphragm. In this study we have examined the potential importance of Na(+)-Ca2+ exchange as a mechanism for Ca2+ influx during the contractile process by studying the effect of inhibition or stimulation of Na(+)-Ca2+ exchange. Blockade of Na(+)-Ca2+ exchange with amiloride attenuated the twitch response, altered the force-frequency response curve, and enhanced the development of fatigue. The effect of amiloride could be partially reversed by increasing the extracellular Ca2+ concentration. The ability of amiloride to decrease force was associated with decreased Ca2+ uptake by the diaphragm. Enhancing intracellular Na(+)-extracellular Ca2+ exchange by inhibiting the Na(+)-K+ pump significantly decreased the rate of the development of muscle fatigue (89%). The maximal inhibition of diaphragmatic force produced by the amiloride analogue benzamil, which possesses 10-fold greater selectivity for Na(+)-Ca2+ exchange, was not significantly different from that produced by amiloride (76.2 +/- 1.1%), with a concentration that decreased maximum force by 50% equal to 46 microM compared with 460 microM for amiloride. Both agents slowed the maximal rate of relaxation up to 90%. Benzamil elevated resting tension during continuous stimulation of the diaphragm at 0.15 Hz. The results suggest that Na(+)-Ca2+ exchange may have a role in the normal function of the diaphragm.
Amiloride↗
Federal science spending priorities: a senator's perspective.
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Financing, Government↗
Fluoride bioavailability from slow-release sodium fluoride given with calcium citrate.
Clinical pharmacology of slow-release sodium fluoride given with calcium citrate was examined in acute and long-term studies. Following a single oral administration of 50 mg slow-release sodium fluoride, a peak serum fluoride concentration (Cmax) of 184 ng/ml was reached in 2 h; thereafter, serum fluoride concentration declined with a T1/2 of 5.9 h. The concurrent administration of calcium citrate (400 mg calcium) gave an equivalent Tmax (time required to attain Cmax) and T1/2, but a lower Cmax of 135 ng/ml. The coadministration of a meal with fluoride also reduced Cmax but increased Tmax. The area under the serum concentration curve of slow-release sodium fluoride was reduced 17-27% by a meal or calcium citrate. Thus, calcium citrate reduced fluoride absorption and peak fluoride concentration in serum of slow-release sodium fluoride but did not affect the time required to reach peak concentration or the rate of subsequent decline. The effect of a meal was similar, except for a longer period required to reach peak serum concentration. During long-term administration of 25 mg slow-release sodium fluoride coadministered with 400 mg calcium as calcium citrate on a twice daily schedule, the trough level of serum fluoride could be kept between 95 and 190 ng/ml, believed to be the therapeutic window.
Adult↗
Daylight saving time in psychiatric illness.
It has been reported that the change in photoperiod induced by the occurrence of daylight saving time has an effect on psychiatric presentation. We therefore investigated the impact of daylight saving time in three conditions: (1) parasuicide presentations; (2) psychiatric outpatient contacts, and inpatient admissions; (3) registered suicides. Results indicate that neither the change in photoperiod nor the effect of a small change in circadian rhythm associated with daylight saving time has an effect on 'cases' in any of the three conditions.
Circadian Rhythm↗
Skeletal muscle limits the exercise tolerance of renal transplant recipients: effects of a graded exercise training program.
Sixteen renal transplant recipients were studied before and after they had participated in a 24-week exercise training program to determine (1) the nature of the factors explaining their impaired exercise tolerance, and (2) their adaptative responses to exercise training. During progressive treadmill exercise to exhaustion prior to training, renal transplant recipients stopped exercising at lower peak rates of oxygen consumption (VO2max) (29.0 +/- 7.8 47.9 +/- 9.1 mL O2.kg-1.min-1; P less than 0.001) and ventilation (55.9 +/- 13.2 v 124.0 +/- 22.2 L.min-1; P less than 0.0001), and at lower peak heart rates (169 +/- 22 v 196 +/- 9 beats.min-1; P less than 0.05) and peak blood lactate concentrations (5.0 +/- 2.1 v 11.5 +/- 4.0 mmol.L-1; P less than 0.001) than did controls. None showed a plateau in oxygen consumption with increasing workload. Exercise time to exhaustion was also significantly shorter in renal transplant recipients (9.5 +/- 1.8 v 16.0 +/- 1.3 min; P less than 0.0001). After training, exercise time to exhaustion (12.0 +/- 2.0 min; P less than 0.001), VO2max (37.5 +/- 4.8 mL O2.kg-1.min-1; P less than 0.05), maximum ventilation rate (68.5 +/- 14.0 L.min-1; P less than 0.05), peak blood lactate concentrations (7.8 +/- 1.8 mmol-L-1; P less than 0.001), and the rate of oxygen consumption at a blood lactate concentration of 2.0 mmol.L-1 (22.5 +/- 2.5 v 16.5 +/- 2.2 mL O2.kg-1.min-1; P less than 0.001) had all increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Adaptation, Physiological↗
An E. coli expression system for the rapid purification and characterization of a v-abl tyrosine protein kinase.
A bacterial expression vector containing a segment of the v-abl gene from Abelson murine leukemia virus (A-MuLV) was constructed such that the gag region of v-abl was replaced by a sequence encoding the IgG-binding domain of the S. aureus protein A. pabl HP, a fusion protein encoded by this vector was rapidly purified to near homogeneity by affinity chromatography on IgG-Affigel and Mono Q FPLC. The Km of the pabl HP kinase for ATP varied with [Val5]-angiotensin II concentration and was 21.2 microM at saturating concentrations of [Val5]-angiotensin II. The Km for [Val5]-angiotensin II at saturating concentrations of ATP was 3.8 mM. The turnover number, at 20 degrees C, was 62 mumol min-1 mumol-1. Initial rate studies support a ternary complex kinetic mechanism for phosphoryl transferase. The substrate specificity of the pabl HP kinase was further characterized using synthetic peptides. This expression system, which enables the rapid purification of recombinant v-abl kinase is suitable for the comparative enzymological study of mutant v-abl enzymes generated by site-directed mutagenesis.
Abelson murine leukemia virus↗
Changing college students' lifestyles in favor of cancer prevention: a case study.
This article describes a case study in the examination of cancer risk reduction behavioral strategies chosen by 272 college students enrolled in the 1987 "How to Avoid Dying from Cancer ... Now and Later" course. The four most commonly selected cancers chosen by these students--breast, colon/colorectal, skin, and lung cancer--and the corresponding self-reported success of the various strategies are reported. The three most successful strategies were breast self-examination, use of sunscreen lotions, and increased awareness of breast cancer. We concluded that the potential of using behavioral self-contracts to induce lifestyle change in favor of cancer prevention is both cost-effective and practical.
Adult↗
The effect of iron and folate therapy on maximal exercise performance in female marathon runners with iron and folate deficiency.
Of the 85 female marathon runners examined in this study, 14 (16%) had serum ferritin levels below 40 ng/ml but only two (2%) had iron deficiency anaemia (haemoglobin below 12 g/dl); 28 (33%) had serum folate levels below 4.8 ng/ml and of these two (2%) had haemoglobin levels below 12 g/dl and 13 (15%) had mean corpuscular volumes greater than 95 fl. One week after treatment with oral folate (5 mg/day) or iron (50 mg of elemental iron/day), serum ferritin and folate levels were normal but maximum oxygen uptake, maximum treadmill running time, peak blood lactate levels and the running speed at the blood 'lactate turnpoint' were not changed from values measured during an identical test performed 1 week earlier. These parameters were also unchanged in a third exercise test performed after a further 10 weeks of treatment. Serum folate or serum ferritin levels in a control (placebo-treated) group with initially high serum ferritin or folate levels fell with placebo treatment but maximum treadmill running time, maximum oxygen uptake values, peak blood lactate levels and the running speed at the blood 'lactate turnpoint' were unchanged. We conclude that biochemical evidence of iron and folate deficiency is relatively common in female distance runners; that 1 week of treatment corrects the biochemical evidence of folate and iron deficiency but that such treatment does not influence maximal exercise performance nor does it alter blood lactate levels during exercise. In the absence of iron deficiency anaemia, iron therapy for reduced serum ferritin levels, or folate therapy for low serum folate levels, may not improve maximal treadmill performance even in trained runners.(ABSTRACT TRUNCATED AT 250 WORDS)
Anemia, Hypochromic↗
A high carbohydrate diet negates the metabolic effects of caffeine during exercise.
We tested the hypothesis that unrecognized nutritional factors might influence the serum free fatty acid response to caffeine. The time course and extent of the serum free fatty acid response to a fatty meal alone, to caffeine ingestion after a high carbohydrate meal, or to caffeine in combination with either a fatty meal or a high carbohydrate meal (the latter following 3 d of a high carbohydrate diet) were studied in six trained runners. The metabolic response to 120 min of exercise at 75% of maximum oxygen consumption after caffeine ingestion was also studied in runners after a high carbohydrate diet and ingestion of a high carbohydrate meal. Serum free fatty acid levels were highest 3 h after caffeine ingestion alone and were lower following a fatty meal with or without caffeine ingestion (P less than 0.05). The high carbohydrate diet combined with the ingestion of a high carbohydrate meal prevented the expected rise in serum free fatty acid levels following caffeine ingestion. The metabolic response to prolonged submaximal exercise was also not influenced by the ingestion of caffeine by subjects who had eaten a high carbohydrate diet. Nutritional factors, in particular the state of the body carbohydrate stores and the simultaneous ingestion of carbohydrate, influence the response of serum free fatty acid levels to caffeine ingestion.
Adult↗
An efficient method for the purification of tumor necrosis factor from rabbit serum.
Tumor necrosis factor (TNF) has been purified to homogeneity from rabbit serum. TNF was isolated by a purification scheme consisting of chromatography on DEAE-Trisacryl M, concentration on an Amicon YM10 membrane filter, molecular exclusion on TSK-3000 SWG (HPLC), and then either by Reversed phase HPLC on a Vydac C 4 column or by hydrophobic interaction chromatography. This procedure gives a recovery of 50% of pure TNF. The purified material has a specific activity of 2 X 10(8) U/mg in vitro and is active in vivo causing necrosis in Meth A sarcoma bearing mice. It gives a single band at a molecular weight of 17.000 on 15% polyacrylamide gel electrophoresis and 40.000 on gel exclusion chromatography at pH 7.0. The protein has a pI of 5.0 and is stable when heated to 70 degrees C for 10 minutes.
Animals↗
The effect of substrates on the inter-domain interactions of the hinge-bending enzyme 3-phosphoglycerate kinase.
A hinge-bending mechanism has been proposed for phosphoglycerate kinase, in which the two domains bend about the connecting 'waist' region. In partially denaturing concentrations of guanidinium chloride the substrate 3-phosphoglycerate stabilises one domain against denaturation and destabilises the other. The reduction of mutual stabilisation of the two domains on binding substrate indicates a freeing of the hinge to allow the protein to take up other states rather than a directive mechanism. The stabilisation of both domains at higher concentrations of ATP at which the enzyme is inhibited supports this mechanism.
Adenosine Triphosphate↗
Attainment of therapeutic fluoride levels in serum without major side effects using a slow-release preparation of sodium fluoride in postmenopausal osteoporosis.
The bioavailability, biochemical effects, and safety of a slow-release preparation of sodium fluoride were examined. In 8 normal volunteers, a single administration of slow-release sodium fluoride (25 mg) caused a slow rise and gradual decline in serum fluoride concentration, thus avoiding sharp peaks produced by a rapid-release preparation. In 37 patients with postmenopausal osteoporosis, serum fluoride concentration was kept within the "therapeutic window" (95-100 ng/ml) during long-term intermittent sodium fluoride (slow-release) therapy (25 mg twice/day, given for 3 months in each 5-month cycle over five cycles). Serum fluoride was also kept within the therapeutic window in 64 patients who took sodium fluoride (slow release) continuously over 12 months. Serum osteocalcin concentration increased progressively during fluoride treatment (correlation coefficient of 0.88, p less than .001 for the relationship between serum osteocalcin and duration of therapy). Side effects to slow-release sodium fluoride therapy, assessed in 101 patients at two study sites, were minor and included diarrhea in 2 patients, nausea in 2 patients, abdominal pain and cramping in 2 patients, foot pain in 2 patients, and joint pain in 6 patients. Thus, slow-release sodium fluoride confers desired level of fluoride in serum, while providing safety of usage.
Aged↗
The influence of weekly training distance on fractional utilization of maximum aerobic capacity in marathon and ultramarathon runners.
This study was designed to examine the interrelationships between performance in endurance running events from 10 to 90 km, training volume 3-5 weeks prior to competition, and the fractional utilization of maximal aerobic capacity (%VO2max) during each of the events. Thirty male subjects underwent horizontal treadmill testing to determine their VO2max, and steady-state VO2 at specific speeds to allow for calculation of %VO2max sustained during competition. Runners were divided into groups of ten according to their weekly training distance (group A trained less than 60 km X week-1, group B 60 to 100 km X week-1, and group C more than 100 km X week-1). Runners training more than 100 km X week-1 had significantly faster running times (average 19.2%) in all events than did those training less than 100 km X week-1. VO2max or %VO2max sustained during competition was not different between groups. The faster running speed of the more trained runners, running at the same %VO2max during competition, was due to their superior running economy (19.9%). Thus all of the group differences in running performance could be explained on the basis of their differences in running economy. These findings suggest either that the main effect of training more than 100 km X week-1 may be to increase running economy, or that runners who train more than 100 km X week-1 may have inherited superior running economy.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Use of a bogus pipeline method to increase accuracy of self-reported alcohol consumption among pregnant women.
Pregnant women (N = 220) attending urban maternity care clinics were randomly assigned to study groups to determine the effectiveness of a "bogus pipeline" method to increase the accuracy of behavioral self-reports of alcohol consumption. Results indicate a significant difference (p less than .025) between those who reported alcohol consumption and those who were told their behavioral self-report of alcohol consumption would be confirmed by a physiological test (bogus pipeline). Only 14% in the self-reported group said they currently used alcohol during pregnancy, whereas 27% in the bogus pipeline group reported consumption of alcohol during pregnancy. The results suggest that the use of the bogus pipeline may increase the accuracy of self-reported alcohol consumption data from a cohort of pregnant women.
Adult↗