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Biomedical subjects

S Haley

Publications and source records attributed to S Haley.

At least 19 recordsLinked to original sources
PubMed2002

In vitro interactions between gamma deltaT cells, DC, and CD4+ T cells; implications for the immunotherapy of leukemia.

BACKGROUND: Gamma deltaT cells contribute to immune defense against infectious organisms and some malignancies, but the process of activation and proliferation of these cells is not well understood. It is known that the immune response of gamma deltaT cells is not MHC-dependent, but is likely based on direct recognition of surface peptides and non-peptide ligands. This study examined whether DCs and CD4(+) T cells can participate in the activation of gamma deltaT cells. METHOD: Peripheral blood gamma deltaT cells were co-cultured with CD34-derived autologous DCs and CD4(+) T cells using contact-dependent cultures and transwell systems. Proliferation, immunophenotyping, and cytotoxicity assays determined the extent of gamma deltaT cell proliferation and cytotoxicity. RESULTS: Human gamma deltaT cells expanded 221.3 +/- 76-fold in cultures with DCs, and 165.7 +/- 76.6-fold with CD4(+) T-cells alone. Proliferation was enhanced (1949.8 +/- 261.3-fold) when gamma deltaT cells were cultured with both DC and CD4(+) T cells. Proliferation was contact-dependent, and resulted in the expansion of V delta1+ or V delta2+ cells cytotoxic against several leukemic cell-lines, but not against allogeneic PHA-induced lymphoid blasts. Ligation of the T-cell receptor with anti-pan-delta Ab significantly up-regulated cytotoxicity against K562, KBM-5 and KG1a, and normal BM, but not against Molt-4, allogeneic EBV-transfected B cells and allogeneic PHA-blasts. Minimal cytotoxic activity was shown against allogeneic marrow colony-forming units granulocyte-macrophage and erythrocyte colony-forming units. CONCLUSION: DCs can participate in the activation of gamma deltaT cells against specific autologous targets, and cytotoxicity can be enhanced by further stimulation via the T-cell receptor.

CD11c Antigen↗
PubMed2001

The biology of cortical granules.

An egg-that took weeks to months to make in the adult-can be extraordinarily transformed within minutes during its fertilization. This review will focus on the molecular biology of the specialized secretory vesicles of fertilization, the cortical granules. We will discuss their role in the fertilization process, their contents, how they are made, and the molecular mechanisms that regulate their secretion at fertilization. This population of secretory vesicles has inherent interest for our understanding of the fertilization process. In addition, they have import because they enhance our understanding of the basic processes of secretory vesicle construction and regulation, since oocytes across species utilize this vesicle type. Here, we examine diverse animals in a comparative approach to help us understand how these vesicles function throughout phylogeny and to establish conserved themes of function.

Amino Acid Sequence↗
PubMed2001

Supplementation of urban home visitation with a series of group meetings for parents and infants: results of a "real-world" randomized, controlled trial.

OBJECTIVE: Home visitation has been shown to be effective in reducing rates of child maltreatment and in enhancing psychosocial outcomes in children and their parents. Even when available, however, it is underutilized by parents in some urban settings. We tested a supplemental 10-session group intervention for its ability to increase active participation in home visitation, enhance the quality of caregiving behavior of parents, and improve social developmental outcome in children. METHOD: A randomized controlled design was utilized, involving two separate cohorts of parents of 3- to 18-month old infants, totaling 148 parent-child dyads. The intervention focused on practical experience in promoting parent-infant attachment relationships. RESULTS: At 6 months follow-up, there was a substantial increase in the proportion of intervention group parents participating in home visitation, compared to parents in the control group (Fisher's exact p = .008). Parents in the intervention group exhibited a trend for improvement in their capacity to appropriately interpret infants' emotional cues (p = .08), independent of the effects of home visitation itself. Attrition in both the treatment and control groups was inversely associated with income and level of education. CONCLUSIONS: Group meetings may constitute an effective means of engaging stressed urban families in home visitation.

Adult↗
PubMed2001

Daily general anaesthesia for radiotherapy in unco-operative patients: ingredients for successful management.

An unco-operative patient requiring daily radiation therapy presents a difficult clinical problem. After reviewing the paediatric oncology literature addressing the use of general anaesthesia for short medical procedures, we have developed checklists of procedural guidelines and monitoring equipment for the safe use of daily anaesthesia in adult patients who require a fractionated course of radiation therapy. We illustrate this by describing the successful treatment of a woman with autism and Hodgkin's disease who required daily general anaesthesia for immobilization during a 4-week course of radiation therapy. Propofol was used as the primary drug and was not associated with any adverse side-effects. There was no development of tolerance.

Adolescent↗
PubMed1999

Economic evaluation of outpatient treatment with low-molecular-weight heparin for proximal vein thrombosis.

BACKGROUND: The safety and efficacy of taking low-molecular-weight heparin at home was previously demonstrated in a clinical trial in which patients with acute proximal deep vein thrombosis were randomized to receive either intravenous standard heparin in the hospital or subcutaneous low-molecular-weight heparin administered primarily at home. Treatment in the home has the potential to substantially reduce the cost to the health care system. METHODS: To conduct an economic evaluation we prospectively collected data on resource use and health-related quality of life (Medical Outcomes Study Short-Form 36) on the 300 patients who formed the trial stratum presenting with proximal vein thrombosis as outpatients, of whom 151 received standard heparin and 149 received low-molecular-weight heparin. The primary viewpoint of the analysis was societal, and costs included health care costs, patient travel costs, and productivity costs as a result of time off work. Costs were assessed over a period of 3 months from randomization. Quality of life was assessed as the change in Short-Form 36 domain scores from baseline to day 7 for each treatment group. All costs are reported in 1997 Canadian dollars. RESULTS: There were 11 recurrent thromboembolic events and 1 bleed in the 151 patients who received standard heparin; the corresponding data for the 149 patients receiving low-molecular-weight heparin were 10 and 4, respectively. The mean cost per patient who received standard heparin was Can $5323 compared with Can $2278 for low-molecular-weight heparin, a total societal cost savings per patient using low-molecular-weight heparin of Can $3045 (95% confidence interval, Can $2012-$4050). There was no difference in quality of life between the 2 groups except for the domain of social functioning, where a greater improvement from baseline to day 7 was observed for the low-molecular-weight heparin group vs the standard heparin group (P =.005). CONCLUSIONS: For patients with acute proximal deep vein thrombosis, treatment at home with low-molecular-weight heparin is less costly than hospital-based treatment with standard heparin. The economic evidence in favor of outpatient treatment with low-molecular-weight heparin exhibits dominance; a situation of reduced cost is created with no compromise in clinical outcomes or patients' quality of life.

Adult↗
PubMed1999

Recurrent venous thrombosis and heparin therapy: an evaluation of the importance of early activated partial thromboplastin times.

BACKGROUND: The presence of an association between early subtherapeutic activated partial thromboplastin times (aPTTs) and recurrent venous thromboembolism (VTE) remains controversial. OBJECTIVE: To determine the relation between early subtherapeutic aPTTs and recurrent VTE in patients who were treated with intravenous (i.v.) unfractionated heparin (UFH). PATIENTS AND METHODS: We studied 961 patients with acute VTE who received i.v. UFH in 3 randomized trials that compared the use of i.v. UFH (loading dose: 5000 U i.v.; initial infusion, 1250-1280 U/h) with that of subcutaneous low-molecular-weight heparin. According to aPTT criteria, patients were classified as being in a subtherapeutic or a therapeutic state during the first 24 and 48 hours of treatment. All episodes of possible recurrent VTE were adjudicated by an independent committee that was unaware of the aPTTs. RESULTS: At 24 hours, in 886 patients who were eligible for the analysis, the rate of recurrent VTE in the subtherapeutic group was 6.7% (11/163) compared with 5.3% (38/723) in the therapeutic group. The odds ratio for recurrence in patients in the subtherapeutic vs the therapeutic group at 24 hours was 1.30 (95% confidence interval: 0.64-2.63; P = .46). At 48 hours, in 917 patients who were eligible for the analysis, the rate of recurrent VTE in the subtherapeutic group was 7.8% (5/64) compared with 5.7% (49/853) in the therapeutic group. The odds ratio for recurrence in patients in the subtherapeutic vs the therapeutic group at 48 hours was 1.32 (95% confidence interval: 0.51-3.44; P = .56). CONCLUSION: In patients with acute VTE who receive an i.v. bolus of 5000 U, followed by a starting dose of at least 1250 U/h of UFH, a subtherapeutic aPTT response during the first 48 hours of treatment is not associated with a large increase in the risk of recurrent VTE.

Aged↗
PubMed1997

Complement-mediated lysis of Plasmodium falciparum gametes by malaria-immune human sera is associated with antibodies to the gamete surface antigen Pfs230.

Antibodies to the sexual-stage surface antigens of Plasmodium falciparum, Pfs230 and Pfs48/45, can abolish the infectivity of gametes to mosquitoes; these antigens have been proposed as candidates for inclusion in a malaria transmission-blocking vaccine. One possible mechanism of antibody-mediated transmission blocking is complement-mediated gamete lysis. We have used a panel of human sera from geographically distinct regions where malaria is endemic to investigate whether this may be a mechanism of naturally acquired transmission-blocking immunity to P. falciparum. By immunoprecipitation, we have shown that antibody recognition of Pfs230 and Pfs48/45 is limited, despite universal exposure to P. falciparum gametocytes. In vitro complement-mediated lysis of P. falciparum gametes was positively associated with the presence of antibodies to Pfs230 but not with antibodies to the N-terminal region of the precursor molecule (Pfs260), which is shed from the gametocyte surface at the time of gametogenesis. Similarly, antibodies to two other gametocyte-specific proteins, Pfs48/45 and Pfg27/25, were not associated with gamete lysis. All sera which mediate gamete lysis contain immunoglobulin G1 (IgG1) and/or IgG3 antibodies to gamete surface proteins as determined by an enzyme-linked immunosorbent assay. These data suggest that Pfs230 is a major target of complement-fixing antibodies which may be important for antibody-mediated transmission-blocking immunity.

Adolescent↗
PubMed1996

Low molecular weight heparin and compression stockings in the prevention of venous thromboembolism in neurosurgery.

Perioperative anticoagulant prophylaxis for postoperative venous thromboembolism (VTE) in neurosurgical patients has not gained wide acceptance due to the fear of intracranial bleeding. Physical methods give a worthwhile reduction of postoperative VTE but there still remains a substantial residual incidence. In other clinical indications, low molecular weight heparins have proven to be effective for prophylaxis of VTE when administered postoperatively, with the advantage of no bleeding enhancement during surgery. Therefore, we performed a multicentre, randomized, double-blind trial in neurosurgical patients to investigate the efficacy and safety of adding a low molecular weight heparin (LMWH), nadroparin, initiated postoperatively, to graduated compression stockings in the prevention of VTE. Deep-vein thrombosis was detected by mandatory venography. Bleeding was determined according to pre-defined objective criteria for major and minor episodes. An adequate bilateral venogram was obtained in 166 of 241 LMWH patients (68.9%) and 179 of 244 control patients (73.4%). A total of 31 of 166 LMWH patients (18.7%) and 47 of 179 controls patients (26.3) had VTE up to Day 10 postoperatively (p = 0.047). The relative risk reduction (RRR) was 28.9%. The rates for proximal deep-vein thrombosis/pulmonary embolism were 6.9% and 11.5% for the two groups, respectively (RRR: 40.2%; p = 0.065). Secondary analyses involved all VTE up to day 56 post-surgery which was detected in 33 patients of 241 in the LMWH group (13.7%) and 51 of 244 control patients (20.9%; RRR 34.5%; p = 0.018). The corresponding percentages for proximal deep-vein thrombosis/pulmonary embolism were 5.8% and 10.2% for the two groups, respectively, giving a RRR of 43.3%; p = 0.36. Major bleeding complications, during the treatment period, occurred in six low molecular weight heparin treated patients (2.5%) and in two control patients (0.8%); p = 0.87. A higher mortality was observed in the low molecular weight heparin group over the 56-day follow-up period (22 versus 10; p = 0.026). However, none of these deaths was judged by a blinded adjudication committee to be related to the study drug. In conclusion, this study demonstrates that the low molecular weight heparin, nadroparin, added to graduated compression stockings results in a clinically significant decrease in VTE without inducing any significant increase of major bleeding.

Anticoagulants↗
PubMed1994

Transmission-blocking antibodies against multiple, non-variant target epitopes of the Plasmodium falciparum gamete surface antigen Pfs230 are all complement-fixing.

We have studied the properties of 16 newly derived monoclonal antibodies (MoAbs) against Pfs230, a gamete surface protein of Plasmodium falciparum and a target of transmission-blocking antibodies. All 16 MoAbs recognized Pfs230 by immunoprecipitation from non-ionic detergent extracts of the protein radio-labelled with 125Iodine. The MoAbs also recognized this protein on Western blots under non-reducing conditions but none of them recognized the protein under reducing conditions. Using an immunoradiometric assay the MoAbs appear to define nine different epitope regions. The MoAbs were tested for their ability to lyse extra-cellular female gametes of P. falciparum isolate 3D7. Eight of the MoAbs, all of isotype IgG2a, mediated complement-dependent lysis of the gametes; seven of the MoAbs, all isotype IgG1, failed to lyse the gametes in the presence of active complement. The eight complement-fixing MoAbs mediated almost total suppression of infectivity of gametocytes of P. falciparum 3D7 to mosquitoes; where tested this suppression was mainly complement-dependent. The seven non-complement-fixing MoAbs had no significant effect on the infectivity of gametocytes of P. falciparum 3D7 to mosquitoes. When tested by immunofluorescence the target epitopes of all the MoAbs were conserved in each of the five different isolates of P. falciparum which were tested.

Animals↗
PubMed1994

IMMUNOLOCALIZATION OF AN ANTIGEN ASSOCIATED WITH THE INVERTEBRATE ELECTROGENIC 2Na+/1H+ ANTIPORTER

Epithelial plasma membranes from crustacean gut, kidney and gills have been shown recently to display an electrogenic 2Na+/1H+ antiporter that differs considerably in its physiological properties from the vertebrate electroneutral 1Na+/1H+ exchange paradigm. In this study, we describe the histological and cytological localization of an antigen associated with invertebrate electrogenic 2Na+/1H+ antiport in lobster (Homarus americanus) tissues using a monoclonal antibody (MAb 11) raised in mice against purified brush border membranes of the hepatopancreatic epithelium. Previous work showed that MAb 11 inhibited electrogenic 2Na+/1H+ and Ca2+/H+ exchange by hepatopancreatic brush border membrane vesicles, but was without effect on Na+-dependent d-glucose transport, suggesting a restricted inhibitory specificity to the cation exchanger. MAb 11 binding occurred at hepatopancreatic epithelial R-cell brush border membranes, at plasma membranes of the antennal gland and gill podocytes, and at vacuolar membranes of hepatopancreatic B- and R-cells, gill nephrocytes and epithelial cells of the antennal gland labyrinth and gill lamellae, as assessed by FITC-labelled secondary antibodies. Control FITC-labelled antibodies raised in mice against vertebrate keratin proteins displayed only weak non-specific binding to the tissues and cells responding intensely to MAb 11, supporting the specific nature of MAb 11 binding to its cognate antigen. The broad histological and cytological distribution of MAb 11 binding to plasma membranes and vacuolar membranes from several lobster organ systems suggests that the physiological activities regulated by its antigen, possibly an element of the invertebrate electrogenic cation exchanger, may be diverse.

Journal Article↗
PubMed1994

Functional performance of young children after traumatic brain injury: a 6-month follow-up study.

OBJECTIVES: A follow-up study is reported of 40 children between the ages of 1 month and 5.6 years who had sustained a brain injury either with (n = 11) or without (n = 29) additional injuries. METHOD: Children and their families were assessed at both 1 and 6 months after hospital discharge with standardized measures of functional performance and family functioning, including the Child Behavior Checklist, the Pediatric Evaluation of Disability Inventory, and the Impact on Family Scale. In addition to within-group analyses, functional outcome was compared to that of a group of 17 children who had sustained non-central nervous system injuries. RESULTS: Mean scores for both groups of injured children were within the average range at both 1-month and 6-month follow-up testing. There was a general trend toward improved performance across the follow-up period, although only a few of these changes reached statistical significance. The effect of the injury as reported by the family was significantly associated with children's function as reflected by number of behavior problems and increased need for caregiver assistance. CONCLUSION: Results point to the need for systematic follow-up of young children after brain injury using sensitive measures to enable early identification of children whose further development may be at risk and to provide support to families whose children are displaying changes in functional behavior.

Brain Injuries↗
PubMed1993

Evaluation of a behavioral medicine consultative treatment for chronic, ruminative vomiting.

This case study evaluated a multicomponent behavioral medicine treatment package for chronic ruminating and vomiting in a 13-year-old child with multiple disabilities. Treatment incorporated dietary and medication manipulations combined with behavioral intervention. The treatment package was designed and evaluated via a consultative model in a residential-care setting. The child's ruminative vomiting decreased steadily with implementation of treatment and reduced rates were maintained 2 years later. This case illustrates collaboration between physicians and psychologists in developing comprehensive behavioral medicine interventions for health-threatening clinical disorders.

Adolescent↗
PubMed1989

Epidural anaesthesia and blood flow velocity in mother and fetus.

Doppler ultrasound has recently been used to assess changes in blood velocity in the uterine and umbilical arteries. Alterations in the ratio of systolic to diastolic velocity (S/D ratio) are believed to reflect changes in placental vascular resistance. We have used this technique to assess potential beneficial or detrimental effects of epidural anaesthesia on blood flow to the placenta. Continuous wave Doppler ultrasound was used to measure the S/D ratio in the uterine and umbilical arteries of 12 patients undergoing epidural anaesthesia prior to elective caesarean section. Anaesthesia was achieved using lidocaine and epinephrine. The S/D ratio in both the uterine and umbilical arteries remained unaltered either by the fluid preload or by the epidural anaesthesia. It is concluded that epidural anaesthesia using this technique has neither a beneficial nor detrimental effect on uterine or umbilical blood velocity in the uncomplicated pregnancy.

Anesthesia, Epidural↗
PubMed1988

Gene exchange in African trypanosomes: characterisation of a new hybrid genotype.

We describe the isolation of a hybrid Trypanosoma brucei clone following the mixed cyclical transmission of two parental clones through tsetse flies. The characterisation of this clone reveals some new facets of the process of genetic exchange in T. brucei. The inheritance of four isoenzyme loci and restriction fragment polymorphisms at two loci was interpretable in 'mendelian' genetic terms, involving meiosis either before or after the genetic exchange event. However, at a further two isoenzyme loci a deviation from mendelian behaviour was observed. Pulse field gel analysis showed that the hybrid clone possessed a new combination of intermediate size chromosomes. Examination of kinetoplast DNA variants showed uniparental kinetoplast inheritance, and with reference to previous work we conclude that the kinetoplast can be inherited from either parent. The nuclear DNA content of the hybrid clone was measured and found to be identical to the parental nuclear DNA contents. This finding, together with the inheritance of isoenzyme and RFLP markers, is discussed with respect to possible models for genetic exchange.

Animals↗