PubMed Health⌕ Search

Biomedical subjects

K Parker

Publications and source records attributed to K Parker.

At least 19 recordsLinked to original sources
PubMed1998

The P2X1 receptor, an adenosine triphosphate-gated cation channel, is expressed in human platelets but not in human blood leukocytes.

Extracellular adenosine triphosphate (ATP) and adenosine diphosphate (ADP) activate multiple types of P2-nucleotide receptors expressed in platelets or leukocytes. Electrophysiological and biochemical studies have indicated expression of the P2X1 receptor, an ATP-gated cation channel, in human and rat platelets, rat basophilic leukemia (RBL) cells, and phorbol myristate acetate (PMA)-differentiated HL-60 myeloid cells. Although these findings suggest that P2X1 receptors are present in both blood leukocytes and blood platelets, the relative levels of P2X1 receptor expression and function in human blood leukocytes and platelets have not been directly characterized. On the basis of both immunoblot analysis and functional assays of P2X1 receptor-mediated ionic fluxes, we report that there is significant expression of P2X1 receptors in human platelets, but not in neutrophils, monocytes, or blood lymphocytes. Thus, unlike platelets and myeloid progenitor cell lines, fully differentiated human blood leukocytes do not express functionally significant numbers of P2X1 receptors, suggesting the downregulation of P2X1 receptor gene expression during the differentiation of phagocytic leukocytes. By contrast, P2X1 receptor expression is strongly maintained during megakaryocytic differentiation and platelet release. Immunoblot analysis indicated that the platelet P2X1 receptor migrates as an approximately 60-kD protein during SDS-electrophoresis under reducing or nonreducing conditions. Treatment of platelet membranes with endoglycosidase-F causes the P2X1 receptor band to migrate as a 46-kD protein, verifying the highly glycosylated nature of the mature receptor protein. Additional studies of nucleotide-induced changes in Ca2+ influx/mobilization demonstrated that the platelet P2X1 receptors are pharmacologically distinct from the well-characterized ADP receptors of these cells. This finding suggests a unique role for these ATP-gated ion channels during hemostasis or thrombosis.

Adenosine Triphosphate↗
PubMed1998

Comparison of three solid phase supports for promoting three-dimensional growth and function of human liver cell lines.

An extracorporeal liver support system will require that liver cells maintain their normal differentiated function. This is more likely to be achieved utilizing a three-dimensional culture configuration rather than a simple monolayer culture. We present data on a human liver cell line attached and maintained on different three-dimensional supports, porous glass (Siran), silicon (Immobasil), and calcium-alginate beads. Albumin, fibrinogen, prothrombin, alpha1-acid glycoprotein and alpha1-antitrypsin secretions were measured. Proliferation was slower on each of the three-dimensional supports than on the monolayer culture. The protein secretion of all 5 proteins was highest in cells encapsulated in alginate; silicon beads supported greater protein secretion than glass. Cells on silicon or within alginate were rounded; those on glass grew in 2 configurations as flattened monolayers and as rounded colonies. Cells in alginate secreted as much protein as the whole liver (e.g., albumin, 14.88 g/10(12) cells/day compared to the whole liver, approximately 12 g/day). Three-dimensional culture of a human liver cell line leads to both proliferation and a high synthetic capacity, an important feature of cells suitable for an extracorporeal liver support system.

Albumins↗
PubMed1997

Deaths caused by bedrails.

OBJECTIVES: To determine how bedrails cause death in order to suggest clinical and ergonomic changes to prevent such deaths and to promote research to improve the use and design of bed systems. DESIGN: A review of reports of adult deaths and injuries from bedrails contained in the United States Consumer Product Safety Commission Death Certificate File and its Reported Incidents File and its National Injury Information Clearinghouse Accident Investigations from 1993 to 1996. Deaths involving the use of vest restraints were excluded. We reconstructed, reenacted, and have graphically depicted major patterns of deaths. A review of the literature to 1966 was also done. RESULTS: The 74 deaths described are categorized into three types: (1) 70% were entrapments between the mattress and a rail so that the face was pressed against the mattress, (2) 18% were entrapment and compression of the neck within the rails, and (3) 12% were deaths caused by being trapped by the rails after sliding partially off the bed and having the neck flexed or the chest compressed. CONCLUSIONS: Deaths from bedrails are underrecognized and preventable clinical events that can occur in any medical setting. Preventing these events will require a unified redesign of the relationships between rails, mattresses, and beds, which are now often assembled and used as separate products. Clinicians can prevent many of these deaths by using bedrails much more judiciously, confirming the proper relationships between beds, rails and mattresses, and using alarms.

Aged↗
PubMed1997

Child psychiatric consultation service to community agencies: a collaborative approach involving three community agencies.

OBJECTIVE: To report the early experience of a multiagency child psychiatric consultation service. METHOD: The program is described, and the demographic characteristics of clients referred to the consultation program over the first 25 months of operation are presented. Referrals were examined for demographics and the questions consultees wanted to have answered. RESULTS: In 59 of 100 consultations, physical and/or sexual abuse was proved or highly suspected. In 82 of the 100 cases, consultees had questions pertaining to management issues. Questions related to diagnostic issues numbered 62, and there were 45 questions about safety issues. CONCLUSION: Effective psychiatric consultations services to rural areas can be established. Once established, the questions of consultees can provide an effective training ground for future community-oriented child psychiatrists.

Adolescent↗
PubMed1996

Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells.

Proteinase 3 is present in high concentration in the primary granules of acute and chronic myeloid leukemia blasts, and may represent a potential T-cell target antigen. We screened proteinase 3 against the binding motif of HLA-A2.1. Based on its high predicted binding, a 9-mer peptide, "PR-1," was synthesized and tested for binding to HLA-A2.1 using the T2 cell line. PR-1 at 100 micrograms/mL significantly increased expression of HLA-A2.1, with median channel of fluorescence increasing from 22 to 294. Binding half-life was determined to be 1,460 minutes by I125-labeled beta 2-microglobulin incorporation. HLA-A2.1+ peripheral blood mononuclear cells from a normal donor were used to generate a T-cell line specific for PR-1. The line demonstrated 85% PR-1-specific lysis at an E:T ratio of 50:1, compared with 20% lysis without PR-1, using T2 cells as targets. It also showed 79% specific lysis to fresh chronic myelogenous leukemia blasts, 54% to fresh acute myelogenous leukemia blasts, and only background lysis (< 20%) to HLA-A2.1+ normal allogeneic marrow cells. The amount of lysis of HLA-A2.1+ myeloid cells was proportional to cytoplasmic proteinase 3 expression. Thus, HLA-A2.1-restricted cytotoxic T cells, raised against a peptide contained in proteinase 3, preferentially lysed fresh human leukemic cells.

Amino Acid Sequence↗
PubMed1996

Strengthening patient education for ORT services in the Central African Republic.

This paper describes the design and implementation of a health worker training program in diarrhea case management and its effect on patient education in health facilities in the Central African Republic (C.A.R.). In 1989, a facility-based assessment of health worker practices in managing diarrheal disease in children under 5 years of age documented serious deficiencies in patient education as performed by health workers. Based on these results, the Ministry of Health (MOH) designed an inservice training program that promoted education as an integral component of curative care. The training program was implemented in all five health regions of the country. An evaluation of the training's impact on the delivery of patient education indicated dramatic increases in the number of messages health workers communicated to mothers. This experience demonstrated that the patient education practices of health workers can be improved through inservice training that integrates the teaching of clinical and communication skills. Additional study in C.A.R. is needed to (1) further improve the quality of patient education for diarrhea and other childhood communicable diseases, (2) determine the impact of patient education on the care provided by mothers in the home following a clinic visit, and (3) assess how operational research can be conducted within the limitations of inservice training programs and routine clinical operations.

Central African Republic↗
PubMed1996

Cumulative trauma disorders among apparel manufacturing employees in the southeastern United States.

Factors associated with cumulative trauma disorders (CTDs) of the upper extremities were studied retrospectively, using data from three apparel manufacturing plants in the southeastern United States. Reported CTDs among the employees at risk during fiscal years 1991 and 1992 were analyzed focusing on individual and plant variables. Results showed that CTD rates increased from 1991 to 1992 and fluctuated in a cyclical pattern each year, peaking during January, March, and August. Employee age and duration of employment were associated with CTD rates. Employees aged 45 to 49 had higher CTD rates than those in any other age groups. Employees with 1 to 3 years' experience had higher CTD rates than employees with more years of service.

Adolescent↗
PubMed1996

MR features of an intracerebellar chloroma.

Granulocytic sarcoma (chloroma) is a rare tumor almost always associated with leukemia. Intraaxial brain lesions are rare, and can mimic infection or primary neoplasm. This intracerebellar chloroma arose after autologous bone marrow transplantation in a 29-year-old woman with leukemia. On T1-weighted MR images, the lesion was isointense with gray matter, and enhanced homogeneously. On T2-weighted and proton density-weighted MR sequences, the center was isointense with gray matter and the periphery was isointense with white matter. The lesion's tendency to remain isointense on sequences with long repetition times is presumably attributable to the presence of myeloperoxidase.

Adult↗
PubMed1994

Phase I trial of an interleukin-2 fusion toxin (DAB486IL-2) in hematologic malignancies: complete response in a patient with Hodgkin's disease refractory to chemotherapy.

BACKGROUND: DAB486IL-2 is a recombinant fusion toxin in which the native diphtheria toxin-receptor binding-domain has been replaced with human interleukin-2 (IL-2). This molecule is specifically cytotoxic in vitro within 30 minutes for cells that express the high-affinity IL-2 receptor (IL-2R). METHODS: This was a Phase I/II study of DAB486IL-2 as a brief infusion in 15 patients with refractory lymphoid malignancies. Five patients per cohort received DAB486IL-2 as a 30-60 minute intravenous infusion at dose levels of 0.075, 0.115, and 0.2 mg/kg daily for 5 days. RESULTS: The maximal tolerated dose (MTD) of DAB486IL-2 was determined to be 0.2 mg/kg daily on the basis of hypersensitivity-like symptoms and reversible hepatic transaminase elevations. Other adverse effects included mild creatinine elevations, proteinuria, and hypoalbuminemia. The presence of antibodies to diphtheria toxin or DAB486IL-2 was correlated with hypersensitivity-like effects but did not prevent an antitumor effect. One complete response was observed in a patient with Hodgkin's disease in relapse with bilateral pulmonary nodules after autologous bone marrow transplantation. He remains free of disease more than 2 years after completion of therapy. CONCLUSIONS: The dramatic antitumor response seen in one patient and the relative tolerability of DAB486IL-2 indicates the potential utility of this targeted agent in IL-2-expressing hematologic malignancies.

Adult↗
PubMed1994

Linkage analysis of idiopathic generalised epilepsy in families of probands with Juvenile Myoclonic Epilepsy and marker loci in the region of EPM 1 on chromosome 21 q: Unverricht-Lundborg disease and JME are not allelic variants.

The locus for Unverricht-Lundborg disease, EPM 1, has recently been mapped to chromosome 21q22.3. A locus, EJM 1, predisposing to idiopathic generalised epilepsy in families of probands with juvenile myoclonic epilepsy has been localised to chromosome 6p by evidence of linkage to the HLA region. However, segregation analysis suggests a two-locus model for JME and evidence has been obtained for genetic heterogeneity within the JME/IGE phenotype. EPM 1 was therefore investigated as a candidate locus in the set of families segregating for IGE and JME which do not show linkage to markers on chromosome 6p. Linkage analysis was carried out in 25 families using three microsatellite DNA markers around the EPM 1 gene region using different models of inheritance. Multipoint linkage analysis provided definite exclusion for 20cM around PFKL, the closet linked marker to EPM 1, under three out of four models tested. These results strongly suggest that the EPM 1 gene is not linked to the phenotype expressed in these families, and therefore that Unverricht-Lundborg disease and juvenile myoclonic epilepsy are not allelic variants.

Adolescent↗
PubMed1994

DNA structure, hydration and dynamics.

Although the double helical model of DNA structure is now 40 years old, there is still considerable effort being made to elucidate the range of conformations that can be adopted by this flexible molecule. We review the current state of our knowledge of DNA structure which is available from both experimental and computational approaches.

DNA↗
PubMed1994

Phase I trial of a genetically engineered interleukin-2 fusion toxin (DAB486IL-2) as a 6 hour intravenous infusion in patients with hematologic malignancies.

DAB486IL-2 is a recombinant fusion toxin, created by replacement of the receptor binding domain sequences of the diphtheria toxin gene with the sequences for human interleukin-2 (IL-2). It selectively binds to and intoxicates cells expressing the high-affinity IL-2 receptor. A total of 17 patients with refractory hematologic malignancies were entered in a phase I study of DAB486IL-2, administered as a 6 hour continuous intravenous infusion on days 1, 2, 8, 9, 15, and 16 of each 28 day cycle. Cohorts of 3 to 6 patients were treated with escalating doses. The starting dose was 0.1 mg/kg/day with increments of 0.1 mg/kg/day per dose level up to 0.3 mg/kg/day. Significant adverse effects included transient asymptomatic elevation of liver transaminases, hypersensitivity, anemia, thrombocytopenia, fever, and creatinine elevation. A partial response of approximately nine months duration was observed in a patient with small cell lymphocytic non-Hodgkin's lymphoma, previously refractory to high-dose chemotherapy and autologous bone marrow transplantation. The observance of antitumor activity in a patient highly refractory to chemotherapy suggests that DAB486IL-2 may have efficacy in selected patients whose malignant cells express the IL-2 receptor.

Adult↗