An audit of teicoplanin use in a district general hospital.
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Anti-Bacterial Agents↗
Biomedical subjects
S Collier
Publications and source records attributed to S Collier.
Discrepancy in CD3-transmembrane peptide activity between in vitro and in vivo T-cell inhibition.
Electrostatic amino acid interactions between receptor subunits within the T-cell antigen receptor (TCR) transmembrane domain are critical for the formation of the TCR-CD3 complex. Core peptide, a short peptide corresponding to the TCR-alpha transmembrane region, containing two positively charged amino acids, is known to inhibit T-cell function in vitro and in vivo. The aim of this study was to examine peptides corresponding to the syntactic transmembrane CD3 region binding to TCR-alpha for their ability to inhibit T-cell activation in vitro and in vivo. Three peptides matching the transmembrane sequence of CD3-delta, -epsilon and -gamma were synthesized and tested in different biological in vitro and in vivo systems for their effect on T-cell activity. The CD3-peptides had no impact on T-cell function in vitro, but surprisingly, decreased signs of inflammation in the adjuvant arthritis rat model in vivo. Preliminary evidence suggests that peptides with CD3 transmembrane-derived sequences can inhibit an immune response as assessed by adjuvant-induced arthritis. The lack of in vitro activity may lead to a wasteful disregard of active compounds in the process of drug discovery and development.
Animals↗
Hormone-replacement therapy use, but not race, impacts the resting and exercise-induced GH response in postmenopausal women.
OBJECTIVE: This study examined the effect of hormone-replacement therapy (HRT) use on the incremental GH response to aerobic exercise in postmenopausal women and established whether racial differences in the GH response were seen at rest and in response to exercise. METHODS: 13 white (n = 6, HRT; n = 7, no HRT) and seven black women (no HRT) were studied on two occasions, a control day and an exercise day (30 min at 70% VO(2)max on a cycle ergometer). Blood was sampled every 10 min for a 4-h period and analyzed for GH using an ultrasensitive chemiluminescent assay. RESULTS: The mean 4-h GH concentration was higher on both study days in the HRT women than the non-HRT users. The integrated GH concentrations were greater in the HRT women both at rest and in response to exercise (rest, 352 +/- 53 min microg l(-1); exercise, 711 +/- 57 min microg l(-1); P < 0.01) than in the non-HRT women (rest, 157 +/- 87 min microg l(-1); exercise, 248 +/- 94 min microg l(-1)). The incremental GH response was greater in the HRT users than in the non-HRT women (358 +/- 130 versus 90.8 +/- 94 min microg l(-1), respectively; P < 0.05). GH-production rate during the 4-h period was greater in the HRT women than in the non-HRT women (P < 0.01), due to an increase in the GH mass secreted/pulse (P < 0.05), with no change in GH pulse number or GH half-life. No racial differences in the mean 4-h GH concentrations or integrated GH concentrations were found at rest or in response to exercise. CONCLUSION: HRT use resulted in a greater incremental exercise response compared with non-HRT users, due to changes in the secretory pulse characteristics in the HRT users. This study also demonstrated that no racial differences exist at rest and in response to exercise in the morning hours.
Bicycling↗
Heart failure (HF): are nurses providing patients with optimal education of self-care principles?
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Journal Article↗
Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients.
OBJECTIVE: To investigate whole body in vivo cysteine kinetics and its relationship to whole blood glutathione (GSH) synthesis rates in septic, critically ill pediatric patients and controls. DESIGN: Prospective cohort study. SETTING: Multidisciplinary intensive care unit and pediatric inpatient units at a children's hospital. PATIENTS: Ten septic pediatric patients and ten controls (children admitted to the hospital for elective surgery). INTERVENTIONS: Septic patients (age, 31 months to 17 yrs) and controls (age, 24 months to 21 yrs) received a 6-hr primed, constant, intravenous tracer infusion of l-[1-13C]cysteine. Blood samples were obtained to determine isotopic enrichment of plasma cysteine and whole blood [1-13C]cysteinyl-glutathione by gas-chromatography mass spectrometric techniques. The plasma flux and oxidation rate of cysteine and the fractional and absolute synthesis rates of GSH were determined. Septic patients received variable protein and energy intake, as per routine clinical management, and controls were studied in the early postabsorptive state. MEASUREMENTS AND MAIN RESULTS: Plasma cysteine fluxes were increased in the septic patients when compared with the controls (68.2 +/- 17.5 [sd] vs. 48.7 +/- 8.8 micromol x kg(-1) x hr(-1); p <.01), and the fraction of plasma cysteine flux associated with oxidative disposal was similar among the groups. The absolute rates of GSH synthesis in whole blood were decreased (p <.01) in the septic patients (368 +/- 156 vs. 909 +/- 272 micromol x L(-1) x day(-1)). The concentration of whole blood GSH also was decreased in the septic group (665.4 +/- 194 vs. 1059 +/- 334 microM; p <.01) CONCLUSIONS: Whole blood glutathione synthesis rates are decreased, by about 60%, in critically ill septic children receiving limited nutritional support. Plasma cysteine fluxes and concentration of cysteine were increased in the septic patients, suggesting a hypermetabolic state with increased protein breakdown. The mechanisms whereby GSH synthesis rates are decreased in these patients are probably multifactorial, presumably involving an inflammatory response in the presence of limited nutritional support. The role of nutritional modulation and the use of cysteine prodrugs in maintaining GSH concentration and synthesis remain to be established.
Adolescent↗
Randomized study comparing the efficacy of a novel manual breast pump with a mini-electric breast pump in mothers of term infants.
The objective of this study was to compare the efficacy of a mini-electric pump (MEP) and a novel manual breast pump (MP) designed to operate more physiologically. Sixty term breastfeeding mothers used the MP and MEP in randomized order 8 weeks postpartum, expressing for 10 minutes from each breast. Milk volume, fat content, and pattern of milk flow were measured. Mothers rated pump characteristics by questionnaire. There was no significant difference in the milk volume or fat content when mothers used the pumps in randomized order. The MP was rated significantly better overall and more comfortable and pleasant to use. Significantly more mothers kept the MP than the MEP. Despite the greater complexity and expense of the MEP, the pumps showed similar efficacy. The MP was preferred by mothers. The novel, more physiological operation of the MP represents an advance in milk expression technology.
Adult↗
Randomized trial comparing the efficacy of a novel manual breast pump with a standard electric breast pump in mothers who delivered preterm infants.
OBJECTIVE: The benefits of human milk for preterm infants are widely recognized, yet technological advances in milk expression have been slow. We compared the efficacy of a standard electric pump (EP; Egnell) used in 94% of United Kingdom neonatal units with a novel manual pump (MP; Avent ISIS) designed to operate more physiologically by simulating the infant's compressive action on the areola during breastfeeding. METHODS: We randomized 145 women who delivered infants of <35 weeks' gestation to use the MP or the EP and measured total milk volume expressed while using the randomized pump during the infant's hospital stay, pattern of milk output and creamatocrit of milk expressed during a test period in the second week, and pump characteristics by maternal questionnaire. RESULTS: Mothers who used the EP, who frequently double pumped, showed shorter expression times but produced no more milk than mothers who used the MP. When both pumped sequentially, however, mothers who used the MP showed significantly greater milk flow and total volume over 20 minutes. Creamatocrit was unaffected by pump type. The MP was rated significantly higher than the EP on 5 major characteristics. CONCLUSIONS: When compared on equal terms (sequential pumping), mothers who used the MP showed greater milk flow, perhaps reflecting more physiologic pump design. Even with double pumping, mothers who used the EP did not advantage their infants with greater milk production. We believe that this novel, effective MP, preferred by mothers and costing a fraction of the EP price, reflects a significant advance in milk expression for high-risk infants.breast pumps, randomized trial, preterm infants.
Breast↗
Quantitative analysis of the neuroendocrine-immune axis: linear modeling of the effects of exogenous corticosterone and restraint stress on lymphocyte subpopulations in the spleen and thymus in female B6C3F1 mice.
The effects of exogenous corticosterone and restraint stress on the number and percentage of lymphocyte subpopulations in the spleen and thymus were evaluated. The data were used to generate linear models that describe the relationship between these parameters and the area under the corticosterone concentration vs time curve (AUC). Comparison of the models revealed that the number of nucleated cells in the spleen was decreased similarly by exogenous corticosterone and restraint (at equivalent corticosterone AUC values). However, exogenous corticosterone caused a greater decrease in cell number in the thymus than it did in the spleen. Corticosterone preferentially depleted CD4+CD8+ cells in the thymus, whereas the same corticosterone exposure produced by restraint stress did not. In the spleen, cell number for all major cell types was decreased by both treatments, but there were minor differences in the change in percentage of some subpopulations induced by exogenous corticosterone as compared to restraint. The models derived here provide quantitative data that indicate the magnitude of corticosterone and stress-induced effects on lymphocyte populations in the spleen and thymus. These results have mechanistic implications, and they may be useful in future efforts to extrapolate from mouse to human by completing a risk assessment parallelogram.
Animals↗
The Drosophila embargoed gene is required for larval progression and encodes the functional homolog of schizosaccharomyces Crm1.
The CRM1 (Exportin 1) protein is a receptor for leucine-rich nuclear export signal sequences. We have molecularly characterized the Drosophila melanogaster embargoed (emb) gene and find that it encodes a product with 49 and 71% sequence identity to the fission yeast Schizosaccharomyces pombe and human CRM1 proteins, respectively. We show that expression of the emb cDNA is sufficient to suppress the growth phenotype of both conditional-lethal and null S. pombe crm1(-) mutant strains, suggesting that emb encodes the functional homologue of the S. pombe Crm1 protein. Through mutagenesis screens we have recovered a series of recessive lethal emb mutations. There is a substantial maternal contribution of emb mRNA and animals hemizygous for our emb alleles can develop to second instar larvae but persist at this stage and consistently fail to undergo the molt to the third instar stage. We see a nuclear accumulation of endogenous actin in the intestinal epithelial cells of the emb mutant larvae, consistent with a role for the emb gene product in nuclear export of actin protein.
Actins↗
The balance between isoforms of the prickle LIM domain protein is critical for planar polarity in Drosophila imaginal discs.
The tissue polarity mutants in Drosophila include a set of conserved gene products that appear to be involved in the control of cytoskeletal architecture. Here we show that the tissue polarity gene prickle (pk) encodes a protein with a triple LIM domain and a novel domain that is present in human, murine, and Caenorhabditis elegans homologs which we designate PET. Three transcripts have been identified, pk, pkM, and sple, encoding 93-, 100-, and 129-kD conceptual proteins, respectively. The three transcripts span 70 kb and share 6 exons that contain the conserved domains. The pk and sple transcripts are expressed with similar tissue-specific patterns but have qualitatively different activities. The phenotypes of pk mutants, and transgenic flies in which the different isoforms are overexpressed show that the balance between Pk and Sple is critical for the specification of planar polarity. In addition, these phenotypes suggest a tessellation model in which the alignment of wing hairs is dependent on cell shape and need not reflect fine-grained positional information. Lack of both pk and sple transcripts gives a phenotype affecting the whole body surface that is similar to those of dishevelled and frizzled (fz) suggesting a functional relationship between pk and fz signaling.
Amino Acid Sequence↗
Forceps and vacuum delivery: expectations of residency and fellowship training program directors.
The objective of this study is to compare current forceps training practices in North American obstetrical residency training programs with that in maternal-fetal medicine fellowship programs. We sent a survey to all obstetrics and gynecology residency training programs and to all maternal-fetal medicine fellowship programs in North America. After sending out 354 questionnaires, 219 were returned for a response rate of 62%. The response rate for fellowship programs (52 of 59; 88%) was significantly greater than that of residency training programs (167 of 295; 56.6%) (p < 0.05). All fellowship training programs were using the 1988 ACOG forceps classification system, as were 98% of the residency training programs. Eighty-five percent of fellowship directors and 80% of residency directors felt the same system should be used for vacuum deliveries. All residency and fellowship directors expected proficiency with both instruments for outlet deliveries. For low deliveries requiring < or =45 degrees of rotation, at least 92% expected proficiency with both instruments. For low-forceps deliveries with >45 degrees of rotation, 82% of fellowship directors and 80% of residency directors expected proficiency. For low-vacuum deliveries with >45 degrees of rotation, 80% of fellowship directors and 76% of residency directors expected proficiency. Significantly more fellowship directors expected midforceps proficiency (47%) than did residency program directors (38%) (p < 0.05). Midvacuum proficiency was expected by 73% of fellowship directors and 69% of residency directors. The ACOG 1988 forceps classification system has now achieved wide acceptance and is taught by both residency and fellowship program directors. Most program directors favor using the same classification system for vacuum extraction deliveries. In general, the expectations of the residency program directors mirror those of maternal-fetal medicine fellowship directors. While outlet and low operations with < or =45 degrees of rotation are taught and proficiency is expected, most programs no longer expect proficiency in midforceps delivery, but do expect proficiency in midvacuum delivery. Proficiency in low operations with rotations < or =45 degrees is still expected.
Adult↗
Quantitative relationships between the suppression of selected immunological parameters and the area under the corticosterone concentration vs. time curve in B6C3F1 mice subjected to exogenous corticosterone or to restraint stress.
The neuroendocrine response to stressors increases the concentration of several endogenous mediators, some of which are immunosuppressive. However, quantitative aspects of these effects have been overlooked. Although it should be possible to predict the degree of suppression of particular immunological functions by measuring the concentrations of stress-related mediators such as corticosterone, this cannot be done with data presently available. This study was designed to develop regression models to predict the relationship between the area under the corticosterone concentration vs. time curve (AUC) and two immunological parameters. Models were developed using mice treated with exogenous corticosterone and mice subjected to various periods of restraint stress. The latter treatment was included to determine if the effects of corticosterone were different from those of corticosterone in association with the other mediators induced in a restraint-stress response. Models relating corticosterone AUC to expression of MHC class II proteins on splenocytes were very similar, whether the corticosterone was exogenous or produced as part of a restraint-stress response. This was also true for splenic natural killer (NK) cell activity. However, MHC class II expression was more sensitive to the effects of corticosterone or restraint than was NK cell activity. The corticosterone and restraint models predicted the previously published effect of a chemical stressor (ethanol) on MHC class II expression, but neither model predicted the suppression of NK cell activity by ethanol. These results have mechanistic implications, which are discussed in the context of previous studies. The quantitative models described here should be useful in determining and predicting the stress-related portion of chemical-induced immunosuppression. In addition, these models provide quantitative data essential for a complete understanding of stress-induced immunosuppression.
Animals↗
The Drosophila tissue polarity gene starry night encodes a member of the protocadherin family.
The tissue polarity genes control the polarity of hairs, bristles and ommatidia in the adult epidermis of Drosophila. We report here the identification of a new tissue polarity gene named starry night (stan). Mutations in this essential gene alter the polarity of cuticular structures in all regions of the adult body. The detailed polarity phenotype of stan on the wing suggested that it is most likely a component of the frizzled (fz) pathway. Consistent with this hypothesis, stan appears to be downstream of and required for fz function. We molecularly cloned stan and found that it encodes a huge protocadherin containing nine cadherin motifs, four EGF-like motifs, two laminin G motifs, and seven transmembrane domains. This suggests that Stan functions in signal reception, perhaps together with Fz.
Amino Acid Motifs↗
T-cell antigen receptor transmembrane peptides modulate T-cell function and T cell-mediated disease.
This study describes a novel method of inhibiting T-cell function by the use of peptides rationally designed from the T-cell antigen receptor (TCR) alpha-chain transmembrane sequence involved with TCR receptor assembly. The most effective peptide (core peptide, CP) modulating in vitro and in vivo T-cell function contained nine amino acids two of which, lysine and arginine, were hydrophilic and separated by four hydrophobic amino acids. CP without chemical modification or conjugation was able to enter non-T and T cells. Conjugation of CP at the carboxyl terminus with palmitic acid resulted in a greater inhibition of T-cell interleukin-2 (IL-2) production in vitro than peptide alone. When examined for effects in vivo, CP reduced clinical signs of inflammation in three T cell-mediated disease models including adjuvant-induced arthritis, experimental allergic neuritis, and cyclophosphamide-induced diabetes in NOD/Lt(F) mice. This peptide or its analogues has potential as a therapeutic agent in human inflammatory and autoimmune disorders.
Amino Acid Sequence↗
Drosophila tissue polarity requires the cell-autonomous activity of the fuzzy gene, which encodes a novel transmembrane protein.
The tissue polarity gene fuzzy (fy) has two roles in the development of Drosophila wing hairs. One is to specify the correct orientation of the hair by limiting the site of prehair initiation to the distal vertex of the wing cell. The other is to control wing cell hair number by maintaining the integrity of the cytoskeletal components that direct hair development. The requirement for fy in these processes is temperature dependent, as the amorphic fy phenotype is cold sensitive. Analysis of mosaic wings has shown that the fy gene product functions cell autonomously. We have cloned the fy transcript, which encodes a novel four-pass transmembrane protein that shares significant homology with proteins encoded by vertebrate cDNAs. The fourth putative transmembrane domain does not appear to play a significant role in tissue polarity as it is deleted in a weak fy hypomorph. Expression of the fy transcript is developmentally regulated and peaks sharply at the time of wing cell pre-hair initiation.
Amino Acid Sequence↗
In vivo evaluation of a resorbable osteoinductive composite as a graft substitute for lumbar spinal fusion.
The purpose of this prospective animal study was to evaluate the efficacy of a resorbable coral particulate to serve as a carrier with several doses of a bovine-derived osteoinductive bone protein mixture. A previously validated rabbit model for posterolateral intertransverse process lumbar spinal fusion was used. Posterolateral intertransverse process arthrodeses were performed at L5-L6 in 64 adult New Zealand white rabbits. The bone graft substitute evaluated consisted of a Biocoral/collagen composite with one of four doses (0, 100, 300, or 1,000 micrograms) of a bovine-derived osteoinductive bone protein extract (BP). Fusions were assessed at 5 weeks by manual palpation, radiography, histology, and biomechanical testing. Use of the Biocoral/collagen carrier without BP resulted in no solid fusions. Biocoral/collagen with 100 micrograms BP resulted in solid fusions in 31% (4 of 13) of the rabbits. Biocoral with 300 micrograms or 1,000 micrograms BP resulted in solid spinal fusion in all rabbits (27 of 27). There were no neurologic complications related to the growth factor or carrier. Small subcutaneous collections of serous fluids were noted in 26% of the animals in the 1st postoperative week, but resolved without problems by the 5th week. Such seromas may limit the clinical utility of this growth factor-carrier combination. Biocoral/collagen combined with the appropriate dose of bovine-derived osteoinductive bone protein was efficacious as a bone graft substitute for achieving posterolateral lumbar spinal fusion in the rabbit model. A dose of 300 micrograms BP was determined as the threshold to reliability produce solid spinal fusions.
Absorption↗
Advances in parenteral nutrition.
Parenteral nutrition is an expensive therapy that is often necessary in certain situations, such as short-bowel syndrome. In many other conditions, its efficacy remains controversial. Providing optimal parenteral nutrition can be particularly challenging in premature infants while managing metabolic and catheter complications. Use of special nutrients, glutamine, and growth hormone may have benefits in the nutritional management of premature infants and trauma patients. Metabolic complications of parenteral nutrition such as cholestasis might be reduced by early enteral feedings, ursodeoxycholic acid, and cholecystokinin-octapeptide. Trace-element deficiencies may still occur, and thus patients must be monitored carefully. Methods that have been used to prevent or reduce catheter occlusion or infection include heparin, oral anticoagulants, antibiotics, and thrombolytic agents such as urokinase and tissue plasminogen activator.
Catheterization↗
Effects of transforming growth factor beta on proteoglycan synthesis by cell and explant cultures derived from the knee joint meniscus.
Repair of meniscal tears depends in part upon the ability of the resident fibrochondrocytes to produce new extracellular matrix molecules including proteoglycans. Three culture systems have been used to investigate proteoglycan production by meniscal fibrochondrocytes from the inner, middle and outer zones of medial and lateral menisci of the sheep stifle joint. Cultures of meniscal explants, monolayered cells, and cells encapsulated in alginate beads were labeled with 35SO4H2 for 48 h in the absence and presence of transforming growth factor beta (TGF beta) and the proteoglycans were analysed by Sephacryl S-1000 chromatography. In general, the lateral meniscus produced more proteoglycan than the medial. Explants from the inner and middle zones produced predominantly aggrecan-like proteoglycan, together with a smaller proteoglycan population eluting with an average distribution coefficient of around 0.65. The outer meniscal zones synthesized less proteoglycan overall, the majority of which consisted of the smaller proteoglycans. These characteristic proteoglycan size profiles obtained with explant cultures also were preserved when cells isolated from the respective zones were cultured in alginate beads. Monolayer cell cultures, however, produced almost entirely small proteoglycans, regardless of their zone of origin. Chromatography of chondroitinase AC and ABC digested samples indicated that the small proteoglycan population comprised mostly dermatan sulphate-containing proteoglycans. In all meniscal zones and in all culture systems, TGF beta stimulated proteoglycan production by up to 100% and the proteoglycans were slightly larger. TGF beta also stimulated cell division in fibrochondrocyte monolayer cultures. Long term intermittent stimulation of alginate bead cultures with TGF beta resulted in large increases in proteoglycan synthesis, increased aggregation of large proteoglycan monomers, and an increase in the production of the larger of two small proteoglycans, putatively, biglycan.
Alginates↗