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Biomedical subjects

D Fisher

Publications and source records attributed to D Fisher.

At least 55 records · Page 3Linked to original sources
PubMed2000

Plasmodium falciparum erythrocyte membrane protein 1 is anchored to the actin-spectrin junction and knob-associated histidine-rich protein in the erythrocyte skeleton.

A distinctive pathological feature of Plasmodium falciparum malaria is the endothelial attachment of erythrocytes infected with mature asexual-stage parasites in microvessels of the major organs. Electron-dense protrusions described as knobs are displayed on the surface of parasitized erythrocytes and act as attachment points in cytoadherence. Parasite-encoded knob-associated histidine-rich protein (KAHRP) is a major component of knobs found on the cytoplasmic side of the host cell membrane. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is a family of parasite-encoded cytoadherence receptors localized to knobs on the surface of parasitized erythrocytes. Despite its high antigenic diversity, PfEMP1 has a remarkably conserved cytoplasmic domain. We demonstrate in this study that the cytoplasmic domain of PfEMP1 (VAR(CD)) binds to host spectrin and actin and to full-length KAHRP in vitro. Apparent dissociation constants determined for VAR(CD)/F-actin and VAR(CD)/KAHRP interactions are 44.9+/-6.4 and 10. 7+/-2.2 nM, respectively. Further, we provide evidence that KAHRP polypeptides self-associate in solution to form structures similar to knobs and show binding of self-associated KAHRP clusters to spectrin-actin-protein 4.1 complexes. Findings in this study suggest that PfEMP1 is localized to the knob in P. falciparum-infected erythrocytes by binding to the host spectrin-actin junction and to self-associated KAHRP through its conserved cytoplasmic domain.

Actins↗
PubMed2000

Pharmacokinetic studies of neuromuscular blocking agents: good clinical research practice (GCRP).

In September 1997, an international consensus conference on standardization of studies of neuromuscular blocking agents was held in Copenhagen, Denmark. Based on the conference, a set of guidelines for good clinical research practice (GCRP) in pharmacokinetic studies of neuromuscular blocking agents is presented. Guidelines include: design of the study; relevant patient groups to investigate; test drug administration, sampling and analysis; pharmacokinetic analysis; pharmacokinetic/pharmacodynamic modeling; population pharmacokinetics; statistics; and presentation of pharmacokinetic data. The guidelines are intended to aid those working in this research area; it is hoped that they will assist researchers, editors of scientific papers, and pharmaceutical companies in improving the quality of pharmacokinetic studies.

Body Temperature↗
PubMed2000

Pretargeted radioimmunotherapy (PRIT) for treatment of non-Hodgkin's lymphoma (NHL): initial phase I/II study results.

Pretargeted radioimmunotherapy (PRIT) was investigated in patients with non-Hodgkin's lymphoma (NHL). The PRIT approach used in this study is a multi-step delivery system in which an antibody is used to target streptavidin to a tumor associated antigen receptor, and subsequently biotin is then used to target 90Y radioisotope to the tumor localized streptavidin. A chimeric, IgG1, anti-CD20 antibody, designated C2B8 or Rituximab, was conjugated to streptavidin (SA) and administered to patients with NHL. Thirty-four hours later, a clearing agent, synthetic biotin-N-acetyl-galactosamine, was administered to remove non-localized conjugate from the circulation. Finally, a DOTA-biotin ligand, labeled with 111In for imaging and/or 90Y for therapy was administered. Ten patients with relapsed or refractory NHL were studied. In three patients, the C2B8/SA conjugate was radiolabeled with a trace amount of 186Re in order to assess pharmacokinetics and biodistribution using gamma camera imaging. Seven patients received 30 or 50 mCi/m2 90Y DOTA-biotin. Re-186 C2B8/SA images confirmed that the conjugate localized to known tumor sites and that the clearing agent removed > 95% of the conjugate from the circulation. Radiolabeled biotin localized well to tumor. Unbound radiobiotin was rapidly excreted from the whole body and normal organs. The mean tumor dose calculated was 29 +/- 23 cGy/mCi 90Y and the average whole body dose was 0.76 +/- 0.3 cGy/mCi 90Y, resulting in a mean tumor to whole body dose ratio of 38:1. Only grade I/II non-hematologic toxicity was observed. Hematologic toxicity was also not severe; i.e., five of the seven patients who received 30 or 50 mCi/m2 of 90Y-DOTA-biotin experienced only transient grade III (but no grade IV) hematologic toxicity. Although six of ten patients developed humoral immune responses to the streptavidin, these were delayed and transient and hence may not preclude retreatment. Six of seven patients who received 30 or 50mCi/m2 90Y achieved objective tumor regression, including three complete and one partial response. The estimate of tumor to whole body dose ratio (38:1) achieved with PRIT in these NHL patients is higher than has been achieved in other studies using conventional RIT. Toxicity was mild and tumor response encouraging. PRIT clearly deserves additional study in patients with NHL.

Adult↗
PubMed2000

An exploration of child sexual abusers' sexual fantasies before and after treatment.

Although there is a substantial literature looking at the relationship between deviant sexual fantasies and child sexual abuse, there is scant previous work that focuses upon the actual content of such fantasies. The present study looks at child sexual abusers' deviant fantasies both pre- and postintervention. Using both qualitative and quantitative methodologies, a description of the frequency and content of, and triggers for, child sexual abusers' deviant fantasies is reported both pre- and postintervention. The implications of this information for subsequent intervention programs is explored.

Adult↗
PubMed2000

Neutrophil sequestration and the effect of hyperbaric oxygen in a rat model of temporary middle cerebral artery occlusion.

A rat model of reversible occlusion of the middle cerebral artery was developed to assess the role of neutrophils and prophylactic hyperbaric oxygen (HBO2) on cerebral injury. Blood flow to the ipsilateral caudate putamen nucleus was reduced by approximately 50% during 2 h of arterial occlusion, but unaffected on the contralateral side. Neutrophil accumulation in brain was documented as myeloperoxidase concentration, which was elevated in both ipsilateral and contralateral cerebral hemispheres at 1 and 46 h after occlusion/reperfusion. HBO2 administered before ischemia at 2.8 atm abs for 45 min, as well as antibody-induced neutropenia, reduced neutrophil accumulation, functional neurologic deficits, and cerebral infarct volume. These data demonstrate that one mechanism for benefit of HBO2 is related to its ability to ameliorate post-ischemic injury by inhibiting neutrophil sequestration. This mechanism should be taken into consideration when choosing partial pressures of oxygen for investigational clinical protocols.

Analysis of Variance↗
PubMed1999

Pulmonary vascular stress from carbon monoxide.

Studies were conducted with rats to investigate whether exposure to carbon monoxide (CO) at concentrations frequently found in the environment caused lung injury mediated by nitric oxide (*NO)-derived oxidants. Lung capillary leakage was significantly increased 18 h after rats had been exposed to CO at concentrations of 50 ppm or more for 1 h. An elevation of *NO during CO exposure was demonstrated by electron paramagnetic resonance spectroscopy. There was a 2.6-fold increase of *NO over control in the lungs of rats exposed to 100 ppm CO. A qualitative increase in the concentration of H2O2 was also detected in lungs during CO exposure, and this change was caused by *NO as it was inhibited in rats pretreated with the nitric oxide synthase inhibitor, Nomega nitro-l-arginine methyl ester (l-NAME). Production of *NO-derived oxidants during CO exposure was indicated by an elevated concentration of nitrotyrosine in lung homogenates. The CO-associated elevations in lung capillary leakage and nitrotyrosine concentration did not occur when rats were pretreated with l-NAME. CO exposure did not change the concentrations of endothelial or inducible nitric oxide synthase in lung and leukocyte sequestration was not detected as a consequence of CO exposure. CO-mediated lung leak and nitrotyrosine elevation were not affected by neutropenia. We conclude that CO exposure elevates the steady-state concentration of *NO in lungs. Consequences from this change include increases in the concentration of reactive oxygen species, production of *NO-derived oxidants such as peroxynitrite, and physiological evidence of lung injury.

Animals↗
PubMed1999

Making assessment relevant to treatment planning: the STS Clinician Rating Form. Systemic Treatment Selection.

This article reports on the development of a computerized, clinician-based method of assessing patient variables that contribute to differential assignment of psychotherapy models. In the current health care environment, omnibus personality tests and current state measures are both expensive and insensitive to most of the empirically defined patient characteristics that have been identified as indicators of different treatment qualities. Moreover, reliance on patient self-report introduces a variety of distortions and limits predictive studies and follow-up assessments to those who are cooperative. These factors limit the usefulness of the currently available procedures. Aptitude-Treatment-Interaction (ATI) research has revealed differential effects of manualized cognitive, interpersonal, and insight-oriented treatments as a function on a select number of relatively specific personality and symptom qualities. A cost- and time-efficient method of measuring these dimensions could increase the power of treatment by identifying in advance those that are likely to be most effective for a given patient. The STS (Systematic Treatment Selection) Clinician Rating Form is a relatively brief, clinician-based measure of a variety of patient dimensions, including subjective distress, various aspects of coping style, and resistance traits. Current data reveal good interrater reliability and adequate levels of discriminant and convergent validity.

Adult↗
PubMed1999

The role of glutathione, membrane sphingomyelin, and its metabolites in oxidative stress-induced calcium "dysregulation" in PC12 cells.

Previous research showed that increasing membrane sphingomyelin (SPH) levels in rat pheochromocytoma (PC12) cells to the same extent as that seen in some brain regions with aging dramatically increases the vulnerability to oxidative stress (OS). These increases in vulnerability were determined by assessing deficits in the ability of these cells to extrude and/or sequester Ca2+ following 30 mM KCl-induced depolarization (recovery). The purpose of the present experiments was to discern whether increasing the levels of particular SPH metabolite(s), i.e., ceramide (Cer), sphingosine (Ssine), or sphingosine-1-phosphate (SPP), or indirectly increasing the concentrations of these metabolites with sphingomylinase (Sase), would interact with the cell's sensitivity to OS induced by low (5 microM) or high (nonlethal, 300 microM) H2O2. In addition, the OS vulnerability was examined as above under decreased SPH levels by exposing the cells to L-cycloserine (Lcc), which prevents SPH synthesis. Both Sase and SPP significantly decreased Ca2+ recovery of PC12 cells after H2O2 exposure. Conversely, Lcc-treated cells showed no further OS-induced decrements in recovery below those seen in controls. SPP significantly decreased glutathione levels (GSH) in the absence of OS. Repletion of GSH with 20 mM N-acetylcysteine significantly attenuated the effect of 5 microM H2O2 on recovery in SPP-treated cells and decreased sensitivity of SPP-treated cells to low doses of OS. Overall, our results suggest a critical role for GSH and SPP in the regulation of OS vulnerability, especially as it relates to Ca2+ homeostasis.

Aging↗
PubMed1999

HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages.

Infection of macrophage lineage cells is a feature of primate lentivirus replication, and several properties of primate lentiviruses seem to have evolved to promote the infection of macrophages. Here we demonstrate that the accessory gene product Nef induces the production of two CC-chemokines, macrophage inflammatory proteins 1alpha and 1beta, by HIV-1-infected macrophages. Adenovirus-mediated expression of Nef in primary macrophages was sufficient for chemokine induction. Supernatants from Nef-expressing macrophages induced both the chemotaxis and activation of resting T lymphocytes, permitting productive HIV-1 infection. These results indicate a role for Nef in lymphocyte recruitment and activation at sites of virus replication.

Adenoviridae↗
PubMed1999

A study of client-focused case management and consumer advocacy: the Community and Consumer Service Project.

OBJECTIVE: The study investigated the provision of client-focused services to community-based clients with schizophrenia and bipolar disorder. It hypothesised that the delivery of more client-focused services would improve client outcome in terms of functioning, disability and satisfaction with services. Client-focused services were developed using an empowerment model of case management and by the addition of consumer advocates. METHOD: Clients referred for case management were randomly allocated to one of three groups: standard case management (n = 35), client-focused case management (n = 39), or client-focused case management plus consumer advocacy (n = 45). Measures of functioning, disability, quality of life, burden of care and service satisfaction were measured at baseline and 12 months. Outcome data were collected concerning number and duration of hospital readmission, crisis intervention and compliance with treatment and services. RESULTS: While there were no differences between the groups on quantitative measures of functioning, disability, quality of life, service satisfaction and burden of care, there were significant between-group differences on qualitative measures of satisfaction with services. CONCLUSIONS: Several methodological difficulties hampered interpretation of the findings. Although clients did not differ on outcome measures of functioning and disability, the group receiving client-focused case management reported greater satisfaction with service delivery.

Adolescent↗
PubMed1999

Findings on routine abdominal ultrasonography in cystic fibrosis patients.

BACKGROUND: Right lower quadrant abdominal pain may pose a diagnostic problem in patients with cystic fibrosis. Abdominal ultrasound examination, used commonly in the diagnostic work-up, may reveal abnormalities of the appendix. However, interpretation of such findings is problematic, because the appearance of the gastrointestinal system during routine examination has not been documented in patients with cystic fibrosis. The purpose of this study was to investigate the findings during routine abdominal ultrasound scans in our cohort of patients with cystic fibrosis and in control subjects. METHODS: Abdominal ultrasound scans were performed prospectively during routine clinic visits in a cohort of patients with cystic fibrosis. RESULTS: Fifty patients aged 10+/-6 years, (range, 0.5-28 years) were examined; 45 had pancreatic insufficiency. Four patients (3 with pancreatic insufficiency) reported right lower quadrant pain at the time of the scan. According to standard ultrasound criteria, the appearance of the appendix was abnormal in 8 patients (16%), 6 had a mucoid appendix, and 2 had a pathologically thickened appendiceal wall. Only 1 of these 8 patients mentioned abdominal pain at the time of the study. Other incidental findings included gallstones (3 patients), intussusception (2 patients), and pancreatic cyst (1 patient). CONCLUSIONS: Abnormalities can be observed during routine abdominal ultrasonographic studies in cystic fibrosis. These findings may not be associated with abdominal pain; their clinical relevance needs further investigation.

Abdomen↗
PubMed1999

Role of nitric oxide-derived oxidants in vascular injury from carbon monoxide in the rat.

Studies were conducted with rats to investigate whether exposure to CO at concentrations frequently found in the environment caused nitric oxide (NO)-mediated vessel wall changes. Exposure to CO at concentrations of 50 parts per million or higher for 1 h increased the concentration of nitrotyrosine in the aorta. Immunologically reactive nitrotyrosine was localized in a discrete fashion along the endothelial lining, and this was inhibited by pretreatment with the NO synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). The CO-induced elevations of aortic nitrotyrosine were not altered by neutropenia or thrombocytopenia, and CO caused no change in the concentration of endothelial NOS. Consequences from NO-derived stress on the vasculature included an enhanced transcapillary efflux of albumin within the first 3 h after CO exposure and leukocyte sequestration that became apparent 18 h after CO exposure. Oxidized plasma low-density lipoprotein was found immediately after CO exposure, but this was not inhibited by L-NAME pretreatment. We conclude that exposure to relatively low CO concentrations can alter vascular status by several mechanisms and that many changes are linked to NO-derived oxidants.

Animals↗
PubMed1999

According to their peers: inclusion as high school students see it.

Inclusive education has been studied from a number of perspectives, including those of general and special education teachers, administrators, and parents. The perspectives of 257 high school students about inclusive education were examined. Results indicate that these students were supportive of inclusive education and recommended the practice. Students also indicated that their peers with disabilities added a dimension of diversity to the school, had become part of the learning community, and needed to be prepared for the future.

Adolescent↗
PubMed1999

Sonographic diagnosis of ureteral tumors.

We present our experience with transabdominal ultrasonographic diagnosis of ureteral tumors. During the years 1989 to 1998, 16 patients were diagnosed as having ureteral tumors. These patients were referred for sonographic examination for evaluation of hematuria (seven patients) or flank pain (four patients) or for follow-up screening in patients who were asymptomatic but at high risk for transitional cell carcinoma because of known past bladder tumor (five patients). Ten of these patients underwent intravenous urography examination, three patients had retrograde pyelography, and 11 patients underwent CT scanning. Ultrasonography revealed the ureteral tumors in all 16 patients, which appeared as hypoechoic intraluminal soft tissue. Three tumors were localized in the upper ureter, four in the middle ureter, and nine in the distal ureter. The degree of ureterohydronephrosis was minimal (two cases), mild (five cases), moderate (eight cases), or severe (one case). Eleven tumors caused local widening of the ureteral diameter. On intravenous urography, four patients had a nonfunctioning kidney, three patients had unexplained ureterohydronephrosis, and three patients showed ureteral filling defects, of which only two had irregular contours. On retrograde pyelography, two patients had filling defects (one of which with smooth margins), and one had a truncated ureter. On CT the tumor was clearly demonstrated in only seven patients. We found that ultrasonography can be a useful diagnostic tool in the workup of ureteral tumors.

Abdominal Pain↗
PubMed1998

Membrane and receptor modifications of oxidative stress vulnerability in aging. Nutritional considerations.

Evidence suggests that oxidative stress (OS) may contribute to the pathogenesis of age-related decrements in neuronal function and that OS vulnerability increases as a function of age. In addition to decreased endogenous protection, increases in OS vulnerability may result from changes in membrane lipids and distribution of receptor subtype. Using a PC-12 cell model system, we have shown that H2O2 or dopamine (DA) exposure induced deficits in the cell's ability to clear (extrude/sequester, E/S) Ca2+ that are similar to those seen in aging. When plasma membrane concentrations of sphingomyelin (SPM) were used, the SPM metabolite, sphingosine-1-phosphate was increased to the same levels as those seen in aging, and enhancement of OS-induced decreases in calcium E/S following KCL depolarization was observed. Differential decreases in CA2+ E/S were also seen following DA-induced OS in COS-7 cells transfected with one of five muscarinic receptor subtypes. Cells transfected with either M1, M2, or M4 receptors showed significantly greater vulnerability to OS (as expressed by greater decrements in calcium E/S and cell death) than those transfected with M3 or M5 receptors. The vitamin E analogue, Trolox, and the nitrone-trapping agent, PBN, were not effective in altering E/S decrements but were effective in preventing cell death 24 h after OS exposure. These findings suggest that putative regional (e.g., striatum and hippocampus) increases in OS vulnerability and loss of neuronal function in aging may be dependent upon membrane SPM concentration and receptor subtype. In related studies, attempts were made to determine whether increased OS protection via nutritional increases in antioxidant levels in rats [using diets supplemented with vitamin E (500IU/kg), strawberry extracts (9.4 g/kg dried aqueous extract, DAE), spinach (6.7 g/kg DAE), or blueberry extracts (10 g/kg DEA for six weeks)] would protect against exposure to 100% O2 (a model of accelerated neuronal aging). Results indicated that these diets were effective in preventing OS-induced decrements in several parameters (e.g., nerve growth factor decreases), suggesting that although there may be increases in OS vulnerability in aging, phytochemicals present in antioxidant-rich foods may be beneficial in reducing or retarding the functional central nervous system deficits seen in aging or oxidative insult.

Aging↗