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Biomedical subjects

J Warren

Publications and source records attributed to J Warren.

At least 19 recordsLinked to original sources

Molecular characterization of a protozoan parasite target antigen recognized by nonspecific cytotoxic cells.

The target cell antigen(s) on tumor cells and on protozoan parasites recognized by NK and nonspecific cytotoxic cells (NCC) has not yet been specifically identified. NCC may be the teleost equivalent of NK cells and IL-2-activated NK cells. A ligand recognized by NCC has been identified. It is expressed on both protozoan parasites and mammalian tumor target cells. In the present study, a protozoan parasite antigen (NK target antigen/NKTag/p46) was purified from Tetrahymena pyriformis and the entire amino acid sequence was deduced from cDNA. Soluble and purified NKTag inhibited NCC lysis of human and mouse transformed target cells. Homology comparisons using Swissprot database revealed that NKTag is a novel protein. Molecular weight computation of the deduced sequence demonstrated that NKTag is a 48.17-kDa protein containing 422 amino acids with relatively high percentages of tyrosine and serine residues. Expression of NKTag on various mammalian tumor target cells, normal tissue, and T. pyriformis was determined using anti-multiple antigenic peptide (MAP) monoclonal antibody (mab) 22A12 [generated against an N-terminal 20-mer (aa 61-80) of p46]. This mab bound to tissue-cultured and tumor cells (YAC-1, IM-9, NC-37, MOLT-4, and U937) with low levels of binding to fish, mouse, and equine cells. Studies were also done to determine if purified and iodinated NKTag bound specifically to NCC. Binding was saturable and specific. These data provide evidence that NCC recognize a target cell ligand which is found on both protozoan and tumor cells. This may provide an explanation as to how NCC (including activated NK cells) recognize a vast array of targets in the absence of haplotype recognition and in spite of a diverse species of origin.

Amino Acid Sequence

Detection of behavioural and emotional problems in deaf children and adolescents: comparison of two rating scales.

The aim of this study was to establish rates of behavioural and emotional problems, and of social maladjustment, in a population of deaf children, particularly in relation to different methods of communication. The parents of 84 children who attended two schools for the deaf took part. They completed the parents' checklist (PCL), a behaviour rating scale for deaf children, and the Child Behaviour Checklist (CBCL), a measure widely used in the general population. The two instruments were significantly correlated on the severity of behavioural and emotional problems, but their previously established cut-off scores detected different rates of possible clinical cases, i.e. children with mental health disorders. According to the CBCL, 40% of children were within the clinical range, and 82% were socially dysfunctional compared with the general population. The PCL identified a much higher percentage (77%) of caseness. Behavioural and emotional problems were significantly higher in Asian children. Although all subjects used sign language, the additional use of speech, which may indicate increased hearing ability, had a protective effect for adolescents. The findings are discussed in relation to the validation of the instruments and the development of intervention programmes for deaf children.

Adolescent

Localization of monocyte chemoattractant peptide-1 expression in the central nervous system in experimental autoimmune encephalomyelitis and trauma in the rat.

Monocyte chemoattractant protein-1 (MCP-1) is a member of the chemokine beta family of chemoattractants that has been shown to play a major role in the initiation of monocyte and T cell inflammation to sites of tissue injury. In this study, we have examined the distribution of MCP-1 expression in inflammation in the central nervous system (CNS) associated with the autoimmune disease experimental autoimmune encephalomyelitis (EAE) and compared the results with those detected in inflammation associated with trauma. In EAE, MCP-1 expression was detected at the onset of inflammation, prior to clinical expression of disease, in lymphocytes and endothelial cells in subarachnoid locations. Monocyte infiltration into these areas appeared 24 h later. After the onset of clinical signs, MCP-1 expression was widely distributed in the spinal cord with levels increasing and decreasing in association with disease activity. Lymphocytes, macrophages, astrocytes, and endothelial cells could be identified as sources of MCP-1 by immunoreactivity and in situ hybridization. A similar close correlation between macrophage infiltration and the levels of mRNA for MCP-1 was found in the CNS of rats subjected to trauma, and in these animals MCP-1 was detected by immunohistochemistry in macrophages and endothelial cells. The results support the conclusion that MCP-1 is an important mediator of inflammation in the CNS.

Animals

Evaluation of immune dependence of anthelmintic treatment of Heligmosomoides polygyrus in CBA/Ca mice.

The efficacy of anthelmintic treatment of adult Heligmosomoides polygyrus was evaluated in immunologically intact and immune-incompetent (T-cell-deprived) CBA/Ca mice. There was no statistically significant difference in the cure rate, in terms of percentage reduction in worm burden, following treatment with pyrantel pamoate and levamisole between normal (57-71% reduction) and immune-incompetent mice (69-78% reduction). The rate of expulsion, and the total number, of worms expelled from infected mice following drug treatment were comparable in normal and deprived mice. The activity of 2 drugs against adult H. polygyrus has been shown to be independent of the immune status of the host. The significance of the mode of actions of drugs and the site of residence of a parasite within the host are discussed.

Animals

Characteristics of troubled youths in a shelter.

The purposes of this descriptive study were to: (a) describe the identifiable characteristics of a population of runaway youths; (b) describe certain aspects of the youths' current and past situations, such as alcohol and drug use/abuse and a history of physical or sexual abuse; (c) identify significant life events by means of the Coddington Life Events Scale (LES); and (d) examine possible ways in which health and mental health practitioners can best assist these youths and their families through times of crisis. A convenience sample of 78 runaway youths was drawn from an available population of 780 youths who were admitted to a runaway shelter, during the 7-month period of the study. The shelter is located in a semiurban community in north central Florida. Data collection instruments included the Structured Clinical Interview Instrument and the LES. These were administered to volunteer youth participants during the face-to-face interviews. Data from the current study support the assertion that many runaway youths live in abusive situations and are exposed to drugs and alcohol from a variety of sources. Furthermore, the high scores on the LES show insurmountable levels of stressful life events that occur at any given time. Researchers recommend that prevention programs focusing on the antecedents of runaway behavior be developed to prevent future runaway episodes.

Adolescent

Psychopathy in instrumental and reactive violent offenders.

Can violent offenders who commit acts of instrumental aggression for goal-oriented purposes such as robbery be distinguished from those who commit acts of reactive (or hostile) aggression in response to provocation? Because violent offenders often have a history of both instrumental and reactive aggression, this study distinguished between offenders with a history of at least 1 instrumental violent offense and offenders with a history of reactive violent offenses. Two studies tested the hypothesis that instrumental offenders would score higher than reactive offenders and nonviolent offenders on R. D. Hare's (1991) Psychopathy Checklist. The first study sample consisted of 106 violent and nonviolent offenders recruited from a medium-security correctional facility. The second study sample consisted of 50 violent offenders referred for pretrial forensic evaluation. In both samples, instrumental offenders could be reliably distinguished from reactive offenders on the basis of violent crime behavior and level of psychopathy. Group differences could not be attributed to participant age, race, length of incarceration, or extent of prior criminal record.

Adult

Mapping of the epitope recognized by non-specific cytotoxic cells: determination of the fine specificity using synthetic peptides.

NCC recognize a conserved target cell antigen (NKTag) expressed on protozoan parasites and on transformed tumour cells. In the present study, synthetic peptides corresponding to N-terminal, C-terminal and internal NKTag(deduced) amino acid sequences were tested for binding and inhibition of NCC lysis of sensitive target cells. A 20-mer peptide equivalent to amino acids (aa) nos. 55-74 specifically inhibited NCC lysis of human EBV transformed target cells (IM-9). Inhibitory effects were nonreversible and concentration dependent, and 30 min pre-incubation produced optimum inhibition. The inhibitory 20-mer peptide was truncated into 17, 14, 10, 9 and 6-mer peptides and tested for inhibition of cytotoxicity. All produced almost complete inhibition except the 6-mer which had no activity. The NKTag sequence required for NCC binding (minimally) consisted of seven amino acids [aa nos 68-74 (ARG-ASN-LEU-THR-PHE-ILE-LEU-)]. The specificity of inhibition and the distribution of target cells expressing NKTag was determined. A 14-mer peptide composed of aa nos 61-74 inhibited lysis of HL-60, IM-9, DAUDI, YAC-1, U937 and NC-37 target cells. Flanking peptides (aa nos 35-54 and 75-94) were negative. Biotinylated aa nos 61-74 bound to NCC effector cells. The recognition requirements for aa sequence versus aa content were determined. Randomization of the aa in the cognate 9-mer obliterated the inhibitory effects. The 17-mer (cognate) synthetic peptide inhibited conjugate formation between NCC and IM-9 targets. These data demonstrate that NCC recognize a conserved antigen determinant on susceptible target cells consisting of a minimum of 7-9 amino acids in the N-terminal region of NKTag.

Amino Acid Sequence

Effect of land-based and water-based fitness programs on the cardiovascular fitness, strength and flexibility of women aged 65-75 years.

The purpose of this study was to determine the effectiveness of a generalized water-based exercise program (WBE) compared to a land-based exercise program (LBE) on improving cardiorespiratory fitness, body composition, forward trunk flexion and strength measurements of elderly women aged 70 +/- 3.2 years (mean +/- SD). Forty-one healthy, sedentary women were selected to participate in the study and were randomly assigned to the LBE or WBE. The 2 groups exercised for 12 weeks, 3 times/week for 45 min. Fitness testing was done before, during and after training, and included measurements of peak aerobic power (VO2 peak), forward trunk flexion, sum of skinfolds, grip strength, curl-ups and push-ups. Between the tests performed before and after training, there were significant improvements in VO2 peak in both groups (p < 0.05) with no significant differences between the groups (p > 0.05). The LBE group also showed a significant improvement in the total number of curl-ups performed (p < 0.05). There were no significant differences in trunk forward flexion, total (right plus left) grip strength, push-ups, waist to hip ratio, sum of skinfolds or body mass index between the tests performed before and after training over time within groups or between groups (p > 0.05). The results show that general exercise interventions resulted in improvements in cardiovascular fitness (for both groups) and abdominal endurance (in the LBE only), but the two exercise programs used were not specific enough or long enough to cause improvements in muscular strength, flexibility or body composition. Furthermore, except for changes in abdominal endurance, the type of exercise venue (land vs. water) did not have a significant effect on the results obtained.

Aged

Bladder dose estimation during intracavitary brachytherapy for carcinoma of the cervix using a single line source system.

The estimation of maximum bladder doses from orthogonal radiographs is unreliable when triple source systems are used for intracavitary brachytherapy (BT) for gynaecological cancers. For single line source systems, the estimation of maximum bladder doses from radiographs should be more reliable due to the radial symmetry of the isodose distribution. A pilot study has been carried out to compare the estimated maximum bladder doses from standard radiographs with data obtained from CT for single line source BT treatments. 12 patients undergoing treatment for carcinoma of the cervix were selected for CT assessment of their bladder doses. For each patient, the dose rates at the International Commission of Radiation Units and Measurements (ICRU) bladder reference point B1 and a second reference point B2 2.5 cm cranially were computed from orthogonal radiographs and were compared with the maximum bladder dose rate as determined by CT scanning. Dose rates were computed for two different source loading patterns: (1) a 6 cm line source with uniformly distributed linear activity along its length; (2) a 6 cm line source with increased activity in the central 2 cm segment. The mean ratio of the maximum CT bladder dose rate to the dose rate at the ICRU reference point B1 on orthogonal radiographs for the line source with uniform linear activity was 1.32 (range 0.62-2.43, SD = 0.54). When the dose rates at both reference points B1 and B2 were considered, the mean ratio of the maximum CT dose rate to the maximum dose rate from radiographs was only 1.05 (range 0.72-1.72, SD = 0.24). For the line source with increased activity in the central segment, the mean ratio of the maximum CT bladder dose rate to the dose rate at B1 was 1.38 (range 0.60-2.63, SD = 0.64). When both B1 and B2 were considered, the variation in the ratio of the maximum CT dose rate to the maximum dose rate from radiographs was considerably smaller (mean ratio = 1.07, range 0.69-1.76, SD = 0.26). For single line source systems, single point dose estimation using the ICRU reference point on orthogonal radiographs will underestimate the maximum bladder dose although the discrepancy is less than for triple source systems. If the ICRU reference point is used in conjunction with a second reference point 2.5 cm cranially, then underestimation of the maximum bladder dose is unlikely to occur as at least one of the points is likely to be a reasonable estimate of the maximum bladder dose.

Brachytherapy

Circumcision.

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Analgesia

Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Society of Critical Care Medicine.

OBJECTIVE: The development of practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit (ICU) setting for the purpose of guiding clinical practice. PARTICIPANTS: A task force of more than 40 experts in disciplines related to the use of analgesic and sedative agents in the ICU was convened from the membership of the American College of Critical Care Medicine (ACCM) and the Society of Critical Care Medicine (SCCM). EVIDENCE: The task force members provided the personal experience and determined the published literature (MEDLINE articles, textbooks, pharmacopeias, etc.) from which consensus would be sought. Published literature was reviewed and classified into one of four predetermined categories, according to study design and scientific value. CONSENSUS PROCESS: The task force met several times as a whole, and numerous times in smaller groups by teleconference, over a 1-yr period to identify the pertinent literature and arrive at consensus recommendations for the whole task force to discuss. Consideration was given to the relationship between the weight of scientific information and the experts' viewpoints. Over the next year, draft documents were composed by a task force steering committee and debated by the task force members until consensus was reached by nominal group process. The task force draft was then reviewed, assessed, and edited by the Board of Regents of the ACCM. After steering committee approval, the draft document was reviewed and approved by the SCCM Council. DATA SYNTHESIS: To facilitate rapid communication of the six recommendations contained within the complete and unabridged practice parameter document, an executive summary was prepared for publication by the ACCM Board of Regents, and this executive summary was approved by the task force steering committee and the SCCM Executive Council. CONCLUSIONS: A consensus of experts provided six recommendations with supporting data for intravenous analgesia and sedation in the ICU setting: a) morphine sulfate is the preferred analgesic agent for critically ill patients; b) fentanyl is the preferred analgesic agent for critically ill patients with hemodynamic instability, for patients manifesting symptoms of histamine release with morphine, or morphine allergy; c) hydromorphone can serve as an acceptable alternative to morphine; d) midazolam or propofol are the preferred agents only for the short-term (< 24 hrs) treatment of anxiety in the critically ill adult; e) lorazepam is the preferred agent for the prolonged treatment of anxiety in the critically ill adult; f) haloperidol is the preferred agent for the treatment of delirium in the critically ill adult. This executive summary selectively presents supporting information and is not intended as a substitute for the complete document.

Adult

Practice parameters for sustained neuromuscular blockade in the adult critically ill patient: an executive summary. Society of Critical Care Medicine.

OBJECTIVE: The development of practice parameters for achieving sustained neuromuscular blockade in the adult critically ill patient for the purpose of guiding clinical practice. PARTICIPANTS: A task force of more than 40 experts in disciplines related to the use of neuromuscular blocking agents in the intensive care unit was convened from the membership of the American College of Critical Care Medicine (ACCM) and the Society of Critical Care Medicine (SCCM). EVIDENCE: The task force members provided the personal experience and determined the published literature (MEDLINE articles, textbooks, pharmacopeias, etc.) from which consensus would be sought. Published literature was reviewed and classified into one of four predetermined categories, according to study design and scientific value. CONSENSUS PROCESS: The task force met several times as a whole, and numerous times in smaller groups by teleconference, over a 1-yr period to identify the pertinent literature and arrive at consensus recommendations for the whole task force to discuss. Consideration was given to the relationship between the weight of scientific information and the experts' viewpoints. Over the next year, draft documents were composed by a task force steering committee and debated by the task force members until consensus was reached by nominal group process. The task force draft was then reviewed, assessed, and edited by the Board of Regents of the ACCM. After steering committee approval, the draft document was reviewed and approved by the SCCM Council. DATA SYNTHESIS: To facilitate rapid communication of the three recommendations contained within the complete and unabridged practice parameter document, an executive summary was prepared for publication by the ACCM Board of Regents, and this executive summary was approved by the task force steering committee and the SCCM Executive Council. CONCLUSIONS: A consensus of experts provided three recommendations with supporting data for achieving sustained neuromuscular blockade in critically ill patients: a) pancuronium is the preferred neuromuscular blocking agent for most critically ill patients; b) vecuronium is the preferred neuromuscular blocking agent for those patients with cardiac disease or hemodynamic instability in whom tachycardia may be deleterious; c) patients receiving neuromuscular blocking agents should be appropriately assessed for the degree of blockade that is being sustained. This executive summary selectively presents supporting information and is not intended as a substitute for the complete document.

Adult

Comparison of a fungal (family I) and bacterial (family II) cellulose-binding domain.

A family II cellulose-binding domain (CBD) of an exoglucanase/xylanase (Cex) from the bacterium Cellulomonas fimi was replaced with the family I CBD of cellobiohydrolase I (CbhI) from the fungus Trichoderma reesei. Expression of the hybrid gene in Escherichia coli yielded up to 50 mg of the hybrid protein, CexCBDCbhI, per liter of culture supernatant. The hybrid was purified to homogeneity by affinity chromatography on cellulose. The relative association constants (Kr) for the binding of Cex, CexCBDCbhI, the catalytic domain of Cex (p33), and CbhI to bacterial microcrystalline cellulose (BMCC) were 14.9, 7.8, 0.8, and 10.6 liters g-1, respectively. Cex and CexCBDCbhI had similar substrate specificities and similar activities on crystalline and amorphous cellulose. Both released predominantly cellobiose and cellotriose from amorphous cellulose. CexCBDCbhI was two to three times less active than Cex on BMCC, but significantly more active than Cex on soluble cellulose and on xylan. Unlike Cex, the hybrid protein neither bound to alpha-chitin nor released small particles from dewaxed cotton fibers.

Amino Acid Sequence

The use of third-party information in forensic assessments: a two-state comparison.

There is virtually no research on the normative characteristics of forensic mental health assessment, despite the significant increase in conceptual and empirical attention devoted to such assessment within the last 10 years. The present study addressed this deficit by examining the use of third-party information, a crucial component of forensic mental health assessment, by forensic clinicians in two states: Florida (a total of 277 evaluations on the issues of competency to stand trial and sanity at the time of the offense) and Virginia (316 evaluations addressing the same legal issues). Evaluations in each state were performed in either a community or a hospital setting. Basic information about the offense, records of prior mental health evaluation or treatment, and specific statements by victims or witnesses were the variables examined comprising "third-party information" in this study. More than three fourths of all evaluations across states and settings incorporated this information. There was less consistency in the use of mental health records and victim/witness statements, with significant differences observed across settings and states. Results are discussed in light of potential influences of state, setting, and study methodology.

Expert Testimony