Experience with the Sarstedt Salivette in salivary steroid determinations.
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Dose-Response Relationship, Drug↗
Biomedical subjects
S Roberts
Publications and source records attributed to S Roberts.
Mechanisms of inhibition of mononuclear cell activation by the iron-chelating agent desferrioxamine.
Iron-withholding by the chelating agent desferrioxamine abrogates the proliferative response of human peripheral blood mononuclear cells (PBMC) to phytohaemagglutinin (PHA). The present study investigated whether desferrioxamine operates late in the activation process or, as recently suggested, at an early stage, by inhibiting the appearance of the interleukin-2 (IL-2) receptor. Human PBMC were stimulated with PHA (10 micrograms/ml) and [3H]thymidine ([3H]TdR) incorporation determined after 66 hr of culture. Greater than 90% inhibition was achieved by concentrations of desferrioxamine as low as 5 mumol/l present throughout culture, while IL-2 receptor expression (anti-Tac), analysed by FACS, was maintained at up to 75% of control levels. 300 mumol/l desferrioxamine present throughout culture abrogated [3H]TdR incorporation and additionally suppressed IL-2 receptor to 10-15% of control levels. In contrast, the same high dose of desferrioxamine when added for 2 hr to cells previously cultured for 66 hr produced 80% inhibition of [3H]TdR incorporation but failed to inhibit expression of the IL-2 receptor. Desferrioxamine rapidly achieved equilibrium across the cell membrane (within 60 min) and chelated 59Fe delivered to activated cells by the transferrin endocytic cycle. These results indicate that desferrioxamine can inhibit T-cell activation either early or late in the process by chelating iron and independently of an effect on the IL-2 receptor. In support of a dual effect of the drug is the finding that at 50 mumol/l, desferrioxamine-enhanced expression of the transferrin receptor occurred, an adaptive response made to intracellular iron depletion, while IL-2 receptor expression was inhibited.
Cell Division↗
Green care. Lights out.
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Conservation of Energy Resources↗
Regulation of the hepatic transferrin receptor in hereditary hemochromatosis.
The liver is the main site of iron accumulation and pathologic sequelae in hereditary hemochromatosis. Whether this is a result solely of inappropriately increased absorption of iron by the gastrointestinal tract or a more generalized regulatory failure of iron balance is unknown. Using immunohistochemical techniques, we have examined the effects of therapeutic changes in liver iron stores on the expression of the hepatic transferrin receptor in hereditary hemochromatosis. Ten patients with untreated hereditary hemochromatosis had no detectable staining for transferrin receptor in their liver biopsies. All had increased hepatic ferritin (mean = 19.9 micrograms per mg protein, range = 1 to 31.7 micrograms per mg protein) and hepatic iron levels (mean = 36.2 micrograms per mg protein, range = 3.6 to 69.9 micrograms per mg protein). In contrast, hepatocyte transferrin receptor was detected in seven patients in whom hepatic iron stores were markedly depleted by venesection (hepatic ferritin mean = 0.32 microgram per mg protein, range = 0.16 to 0.53 microgram per mg protein; hepatic iron mean = 0.98 microgram per mg protein, range = 0.3 to 2.1 micrograms per mg protein). Sequential data from one patient confirmed the reexpression of receptor in response to therapeutic iron depletion, whereas data from another patient studied during treatment illustrated a reciprocal relationship between liver tissue distribution of iron and expression of transferrin receptor. The finding that appropriate physiologic regulation of the hepatic transferrin receptor operates in hereditary hemochromatosis does not support the concept of a generalized defect in receptor-mediated uptake of transferrin-bound iron.
Antibodies, Monoclonal↗
Storage of pooled platelet concentrates. In vitro and in vivo analysis.
The use of sterile connecting devices will permit up to 5-day storage of pooled platelet concentrates (PCs). However, there are no data evaluating long-term storage of PCs pooled from multiple donors. Four units of ABO-compatible or -incompatible PCs were pooled and stored in single 300-ml PL-732 storage bags for up to 5 days. Results of in vitro assays showed acceptable storage values regardless of the ABO types in the pool. Pool pH on Day 5 was 6.83 +/- 0.3 (mean +/- 1 SD). The in vitro storage characteristics were comparable to those of unpooled age-matched platelets reported previously from our laboratory. For in vivo studies, 4-unit pools of ABO-compatible random-donor PCs stored for up to 96 hours in 1000-ml PL-732 bags were transfused into patients who were thrombocytopenic due to bone marrow failure, and the correct count increments (CCI) were determined. In vivo results showed a mean 1-hour CCI of 11,368 +/- 5824 for the pooled stored platelets and 7819 +/- 5189 for unpooled controls (p greater than 0.05). To evaluate the possibility that passenger lymphocytes in the concentrates would generate mixed lymphocyte reactions (MLR) in the pooling bag during storage, lymphocytes were studied over 5 days of storage by the use of monoclonal antibodies against activated T-cell markers and by 3H thymidine uptake. Results failed to show evidence of either the generation of activated T-cell markers or the uptake of 3H thymidine.(ABSTRACT TRUNCATED AT 250 WORDS)
ABO Blood-Group System↗
Comparison of physical and physiological characteristics in elite young and mature cyclists.
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Adolescent↗
Neuroendocrine responses of type A individuals to exercise.
Ten Type A and 10 Type B individuals exercised for 20 minutes on a bicycle ergometer at 40%, 60%, and 80% of maximal capacity to determine if differences in neuroendocrine reactivity exist. Pre-exercise plasma concentrations of beta-endorphin and epinephrine were similar for Type As and Type Bs. Pre-exercise plasma levels of norepinephrine tended to be higher for the Type As (p less than 0.07). Post-exercise plasma epinephrine concentrations were similar for As and Bs for all trials. The 40% and 60% trials resulted in no differences in post-exercise norepinephrine and beta-endorphin levels for the Type As and Bs. Conversely, the 80% trials resulted in significantly greater norepinephrine and beta-endorphin concentrations for the Type As (p less than 0.05). Plasma serotonin levels at rest and during exercise were always lower for the Type As (p less than 0.05). These results suggest that our Type As had a greater neuroendocrine response to high-intensity exercise than our Type Bs. The greater reactivity and analgesia may allow the Type A person to suppress feelings of fatigue, thus enduring higher levels of exertion for longer periods of time.
Adult↗
Biochemical and structural properties of the cartilage end-plate and its relation to the intervertebral disc.
The cartilaginous end-plate is thought to play an important role in the nutrition of the intervertebral disc, and hence may be of significance in the etiology of back pain. The present study describes the biochemical and histologic properties of the end-plate and adjacent tissues in the young human adult lumbar spine. Thus, a datum is established in which to demonstrate variation with location and relationships between properties of different tissues. Results of the chemical analyses show a change in composition through the end-plate with that at the outer annulus and nearer the bone, having higher collagen but lower proteoglycan and water contents, than the end-plate nearest the disc at the nucleus. Histology demonstrated numerous disruptions along the end-plate, with Schmorl's nodes being present in several specimens. Where these occurred, the disc, and in some cases the end-plate, showed loss of proteoglycan compared with the surrounding tissue.
Adolescent↗
Cortical rotation of the Xenopus egg: consequences for the anteroposterior pattern of embryonic dorsal development.
We first review cortical-cytoplasmic rotation, a microtubule-mediated process by which the Xenopus egg, like other amphibian eggs, transforms its polarized cylindrical symmetry into bilateral symmetry within the first cell cycle after fertilization. This transformation, the earliest of many steps leading to dorsal development, involves the displacement of the egg's cortex relative to its cytoplasmic core by 30 degrees in an animal-vegetal direction. As rotation is progressively reduced by microtubule-depolymerizing agents, embryos develop with body axes progressively deleted for dorsal structures at the anterior end. With no rotation, ventralized embryos are formed. In an effort to comprehend this progressive effect on embryonic organization, we go on to review subsequent developmental process depending on rotation, and we propose, with evidence, that reduced rotation leads to a reduced number of vegetal dorsalizing cells, which induce during the blastula stage a Spemann organizer region of smaller than normal size. The reduced organizer then promotes a reduced amount of cell rearrangement (morphogenesis) at gastrulation. Reduced morphogenesis seems the proximate cause of the incompleteness of axial pattern, as shown further by the fact that embryos that are normal until the gastrula stage, if exposed to inhibitors of morphogenesis, develop body axes that are progressively less complete in their anterior dorsal organization the earlier their gastrulation had been blocked. We discuss why axial pattern might depend systematically on morphogenesis.
Animals↗
Ferritin iron kinetics and protein turnover in K562 cells.
The binding, incorporation, and release of iron by ferritin were investigated in K562 cells using both pulse-chase and long term decay studies with 59Fe-transferrin as the labeled iron source. After a 20-min pulse of labeled transferrin, 60% of the 59Fe was bound by ferritin with the proportion increasing to 70% by 4 h. This initial binding was reduced to 35% when the cells were exposed to the chelator desferrioxamine (5 mM) for an additional 30 min. By 4 h the association of 59Fe with ferritin was unaffected by the presence of the chelator, and levels of 59Fe-ferritin were identical to those in control cells (70%). Between 4-10h there was a parallel decline in 59Fe-ferritin in both control and desferrioxamine-treated cells. When incoming iron was bound by ferritin it was, therefore, initially chelatable but with time progressed to a further, nonchelatable compartment. In turnover studies where ferritin was preloaded with 59Fe by overnight incubation, 50% of the label was released from the protein by 18 h, contrasting with a t 1/2 for cellular iron release of approximately 70 h. The half-time of 59Fe release from ferritin was accelerated to 11 h by the presence of desferrioxamine. The half-time for ferritin protein turnover determined by [35S]methionine labeling was approximately 12 h in the presence or absence of the chelator. Thus, when the reassociation of iron with ferritin was prevented by the exogenous chelator there was a concordant decay of both protein and iron moieties. The direct involvement of lysosomes in this turnover was demonstrated by the use of the inhibitors leupeptin and methylamine which stabilized both 59Fe (t 1/2 = 24 h) and 35S (t 1/2 = 25.6 h) labels. We conclude that in this cell type the predominant mechanism by which iron is released from ferritin is through the constitutive degradation of the protein by lysosomes.
Animals↗
The sqt-1 gene of C. elegans encodes a collagen critical for organismal morphogenesis.
Different mutations in the sqt-1 gene of C. elegans can lengthen, shorten, or helically twist the entire animal. We have cloned the sqt-1 gene and have shown that it encodes a collagen. sqt-1 was localized to a 35 kb region of DNA by physical mapping of chromosomal deficiencies. A transposon (Tc1)-induced mutation of sqt-1 was generated and utilized to identify the sqt-1 gene within this 35 kb region. Sequence analysis of the sqt-1 gene shows that it encodes a 32 kd collagen polypeptide that is similar in size and structure to other members of the C. elegans collagen family. The Tc1 insertion mutant has no detectable sqt-1 transcripts, yet it is morphologically normal, indicating that the null phenotype of sqt-1 is wild type. These results demonstrate that collagen mutations can have dramatic effects on organismal morphology.
Alleles↗
Chelation of transferrin iron by desferrioxamine in K562 cells. The partition of iron between ferrioxamine and ferritin.
In this study we have determined whether desferrioxamine can chelate iron delivered to human leukaemic cells by the transferrin endocytic cycle. The cellular uptake of desferrioxamine was investigated by an indirect method in which the conversion of repeated pulses of [59Fe]transferrin to [59Fe]ferrioxamine was determined at two concentrations of the drug. Maximum generation of [59Fe]ferrioxamine occurred in cells exposed to either 100 microM- or 500 microM-desferrioxamine after 40-60 min. Thereafter (up to 180 min) [59Fe]ferrioxamine levels remained steady with 20% of a 59Fe pulse partitioning to chelator at 100 microM and 50% at 500 microM. Of the cellular [59Fe]ferrioxamine loss 50% occurred within 90-120 min. In cells preloaded with desferrioxamine for 1 or 4 h the partitioning of iron during a 3 h incubation with [59Fe]transferrin was dependent upon the extracellular concentration of the chelator. Above 1 mM more than 80% of entering iron was converted to ferrioxamine and less than 5% partitioned to ferritin. Below this concentration (50-500 microM) a proportion of the iron became ferritin associated (7-41%). There was a linear increase in the total amount of intracellular [59Fe]ferrioxamine in accordance with cellular iron uptake showing that transferrin continued to cycle in the presence of high concentrations of desferrioxamine. The uptake of iron and generation of ferrioxamine were markedly reduced by 5 mM-methylamine, which prevented endosome acidification and uncoupling of iron from endocytosed transferrin.
Animals↗
Assessing continuing education needs of five allied health professions in rural California.
Meeting the needs of rural health care professionals for continuing education remains a challenge for health planners. An assessment of these needs is the focus of this survey of rural practitioners. A continuing education needs survey of five allied health professions in an agricultural region of California was conducted. Variables selected related to professional education and retention and included paramedics, physical therapists, pharmacists, clinical psychologists, and medical technologists. Results indicated a strong need for high quality, moderate cost, locally offered continuing education seminars. Access to professional literature searches was also regarded as important. Several of the selected health profession groups were concerned about maintaining licensure; most intended to remain in their professions for at least six to ten years. These survey findings clearly suggest a need for centrally coordinated continuing education opportunities for allied health personnel in rural service delivery areas.
Allied Health Personnel↗
Engineering antibody affinity and specificity.
A combination of ab initio calculations, "knowledge-based prediction", molecular graphics and site-directed mutagenesis has enabled us to probe the molecular details of antibody:antigen recognition and binding and to alter the affinity and specificity of an antibody for its antigen. The significance of electrostatic hydrogen bonding, hydrophilic/hydrophobic patch matching and van der Waals interactions as well as CDR:CDR interactions are discussed in relation to the results of site-directed mutagenesis experiments on the anti-lysozyme antibody Gloop2. The ability to generate reconstructed antibodies, chimeric antibodies, catalytic antibodies and the use of modelled antibodies for the design of drugs is discussed.
Animals↗
A study of peri-operative patient care.
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Humans↗
Echocardiographic estimate of left atrial pressure in children.
Echocardiographic estimates of left atrial pressure using the Q-MVC/AVC-E ratio were obtained from 21 patients in the early postoperative period and compared to simultaneously recorded mean left atrial pressure. A good correlation was obtained between mean left atrial pressure and the Q-MVC/AVC-E ratio (r = 0.81, p less than 0.001) with a regression equation of: left atrial pressure = 11.09 (Q-MVC/AVC-E) + 0.84. The present data compared to those of previous investigators reveal that, although there are quantitative differences between each of the studies, the correlation coefficient of each study is good. Echocardiography provides a useful noninvasive estimate the left atrial pressure; however, each laboratory must establish its own normals.
Blood Pressure↗
Less-than-expected variability in evidence for three stages in memory formation.
Gibbs and Ng (1976, 1977) proposed a three-stage model of long-term memory formation on the basis of results from a one-trial-learning passive-avoidance procedure using chicks. Chisquare tests show that much of the evidence for this model (Gibbs & Ng, 1976, 1977, 1979, 1984a, 1984b), involving transient drops in retention and drug effects, is less variable than would be expected by chance. This should reduce belief in the model.
Animals↗
Hard times--hard choices: positive decision-making for part-time women doctors.
In an increasingly competitive medical market-place, one of the authors had observed that women applying for training posts often appear lacking in self-confidence and unclear in decisions concerning their career plans. A successful workshop was held for women training part time which provided a forum for individuals to identify and explore their career dilemmas and an opportunity to make some quantitative assessment of their attitudes. Questionnaires completed by the 22 attenders and a further 16 returned by post showed that the majority of this group had realistically thought out career plans, had resolved the dilemmas posed by combining career and family commitments and were clear that their eventual career goal was to become a Consultant in the National Health Service. A much smaller group of women who tended to be both older and occupying more junior grades emerged as being confused about how the career/children conflict could be resolved and unclear as to their career aims. The oft-stated assumption that 'most women prefer a job with less responsibility than a Consultant' was not supported but it is clear that if women are not to be nudged into career cul-de-sacs they need clear advice and information so that they can complete their training and compete successfully with their male colleagues for career posts.
Attitude of Health Personnel↗